1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT DIVISION ONE (1) 2 3 JOYCE FENTRESS, ET AL. PLAINTIFFS 4 5 VS. DEPOSITION FOR PLAINTIFFS 6 7 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 8 * * * * * * * * * * 9 10 DEPONENT: DR. JOE WERNICKE 11 DATE: AUGUST 25 AND 26, 1994 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 20 (502) 589-2273 Page 1 1 * * * * * * * * * * 2 3 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 4 INDIANAPOLIS DIVISION 5 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 6 Litigation ) 7 * * * * * * * * * * 8 NO. 91-02496-A 9 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 10 V. ) DALLAS COUNTY, TEXAS ) 11 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 12 * * * * * * * * * * 13 NO. 92-14775-E 14 RICHARD HAROLD CROSSETT, JR., ) IN THE 15 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT, ) COURT OF 16 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 17 JOCQUETTA ANN CROSSETT, DECEASED ) ) 18 V. ) DALLAS COUNTY, ) TEXAS 19 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 20 PSYCHIATRIC COMPANY, INC. ) D/B/A/ HCA WILLOW PARK ) 101ST JUDICIAL 21 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D. ) Page 2 1 * * * * * * * * * * 2 NO. A-921,405-C 3 MARIA GUADALUPE REVES ) IN THE 4 INDIVIDUALLY AND AS NEXT ) DISTRICT COURT FRIEND OF GRANT JULIAN REVES ) OF 5 A MINOR CHILD, AND ON BEHALF ) OF THE ESTATE OF CHRISTIAN ) 6 MARIE REVES, DECEASED ) ) ORANGE COUNTY, 7 V. ) TEXAS ) 8 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, RAVIKUMAR ) 9 KANNEGANTI, M.D., HOSPITAL ) CORPORATION OF AMERICA, A ) 10 TENNESSEE CORPORATION, HEALTH ) SERVICES ACQUISITION CORP., ) 11 A DELAWARE CORPORATION, ) HCA PSYCHIATRIC COMPANY, A ) 12 DELAWARE CORPORATION, TEXAS ) PSYCHIATRIC CO., INC.. A/K/A ) 13 AND/OR D/B/A HCA BEAUMONT ) NEUROLOGICAL HOSPITAL, AND HCA ) 14 HEALTH SERVICES OF TEXAS, INC. ) 128TH JUDICIAL A/K/A AND/OR BEAUMONT ) DISTRICT 15 NEUROLOGICAL HOSPITAL ) Page 3 1 * * * * * * * * * * 2 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS 3 COUNTY DEPARTMENT - LAW DIVISION 4 RENATO DI SILVESTRO, Individually ) and as Special Administrator of ) 5 the Estate of JOHN DI SILVESTRO, ) Deceased, ) 6 ) Plaintiff, ) 7 ) v. ) No. 91 L 7881 8 ) ROBERT L. NELSON, et al., ) 9 ) Defendants, ) 10 ) GEORGE MELNICK, M.D. and PETER ) 11 FINK, M.D. ) ) 12 Respondents in Discovery.) 13 * * * * * * * * * * Page 4 1 IN THE CIRCUIT COURT OF THE SIXTH JUDICIAL CIRCUIT CHAMPAIGN COUNTY, ILLINOIS 2 LINDA GARDNER, Individually and ) 3 as Special Administrator of ) the Estate of SHANE GARDNER, ) 4 deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91 L 1066 ) 7 ELI LILLY AND COMPANY, a foreign ) corporation, ) 8 ) Defendant. ) 9 10 * * * * * * * * * * Page 5 1 SUPERIOR COURT OF THE STATE OF CALIFORNIA 2 FOR THE COUNTY OF LOS ANGELES 3 DR. MARIUS SAINES, etc., et al., ) Case No: 4 ) SC 008331 Plaintiffs, ) 5 ) vs. ) 6 ) ELI LILLY & COMPANY, a corporation; ) 7 DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1- ) 8 100, inclusive, ) )@- Page 6 1 * * * * * * * * * * 2 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS 3 CIVIL COURT DEPARTMENT 4 EUGENE HUSLIG, AS ADMINISTRATOR ) 5 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 6 HUSLIG, DESCEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 7 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 8 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 9 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 10 ) 94 C 192 PLAINTIFFS, ) 11 ) VS. ) 12 ) COURT NO. 7 MARY L. BILLINGSLEY, EXECUTOR OF ) CHAPTER 60 13 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 14 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 15 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 16 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 17 ) DEFENDANTS. ) Page 7 1 * * * * * * * * * * 2 3 CAUSE NO. 93-04911-A 4 LINDA JILL WELCH, CARLINDA 5 WELCH REX, CONNAN ROSS WELCH AND CHAD MICHAEL WELCH, 6 INDIVIDUALLY AND AS SURVIVORS AND STATUTORY BENEFICIARIES 7 OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 8 V. 9 ELI LILLY AND COMPANY, DISTA PRODUCTS COMPANY, NOE NEAVES, 10 M.D., AND MINITH-MEIER CLINIC, P.A. DEFENDANTS Page 8 1 THE DEPOSITION OF DR. JOE WERNICKE, TAKEN 2 AT THE OFFICES OF MEHAFFY & WEBER, ONE ALLEN 3 CENTER, 500 DALLAS STREET, SUITE 1200, HOUSTON, 4 TEXAS, 77002, ON AUGUST 25 AND 26, 1992; SAID 5 DEPOSITION TAKEN PURSUANT TO NOTICE IN ACCORDANCE 6 WITH THE RULES OF CIVIL PROCEDURE. 7 * * * * * * * * * * 8 A P P E A R A N C E S 9 10 PAUL SMITH COUNSEL FOR PLAINTIFFS 11 745 CAMPBELL CENTER 2 8115 NORTH CENTRAL EXPRESSWAY 12 DALLAS, TEXAS 75206 13 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 14 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 15 STEVE LORE 16 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 17 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 18 ATLANTA, GEORGIA 30308-3243 Page 9 1 BEATRICE M. SMITH 2 ALLISON SPRUIL COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 3 BARTLETT & FRIEND, LLP 1301 MCKINNEY, SUITE 2900 4 HOUSTON, TEXAS 77010 5 BARTON BROWN COUNSEL FOR DR. BILLINGSLEY 6 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 10111 W. 87TH ST. 7 P.O. BOX 12290 OVERLAND PARK, KANSAS 66282 Page 10 1 I N D E X 2 3 DEPOSITION OF DR. JOE WERNICKE 4 5 6 DIRECT EXAMINATION BY MR. SMITH 13 7 EXAMINATION BY MS. ZETTLER 490 8 CERTIFIED QUESTION 73 9 10 CERTIFICATE OF SERVICE 529 11 12 ERRATA 530 13 14 EXHIBITS 15 PLAINTIFFS' EXHIBIT NO. 1.................117 16 PLAINTIFFS' EXHIBIT NO. 2.................127 PLAINTIFFS' EXHIBIT NO. 3.................129 17 PLAINTIFFS' EXHIBIT NO. 4.................213 PLAINTIFFS' EXHIBIT NO. 5.................235 18 PLAINTIFFS' EXHIBIT NO. 6.................251 PLAINTIFFS' EXHIBIT NO. 7.................259 19 PLAINTIFFS' EXHIBIT NO. 8.................263 PLAINTIFFS' EXHIBIT NO. 9.................273 20 PLAINTIFFS' EXHIBIT NO. 10................295 PLAINTIFFS' EXHIBIT NO. 11................309 21 PLAINTIFFS' EXHIBIT NO. 12................342 PLAINTIFFS' EXHIBIT NO. 13................344 22 PLAINTIFFS' EXHIBIT NO. 14................378 PLAINTIFFS' EXHIBIT NO. 15................392 23 PLAINTIFFS' EXHIBIT NO. 16................405 PLAINTIFFS' EXHIBIT NO. 17................408 24 PLAINTIFFS' EXHIBIT NO. 18................417 PLAINTIFFS' EXHIBIT NO. 19................422 Page 11 1 PLAINTIFFS' EXHIBIT NO. 20................427 PLAINTIFFS' EXHIBIT NO. 21................440 2 PLAINTIFFS' EXHIBIT NO. 22................454 PLAINTIFFS' EXHIBIT NO. 23................456 3 PLAINTIFFS' EXHIBIT NO. 24................469 PLAINTIFFS' EXHIBIT NO. 25................481 4 PLAINTIFFS' EXHIBIT NO. 26................487 PLAINTIFFS' EXHIBIT NO. 27................501 5 PLAINTIFFS' EXHIBIT NO. 28................507 PLAINTIFFS' EXHIBIT NO. 29................509 6 PLAINTIFFS' EXHIBIT NO. 30................511 PLAINTIFFS' EXHIBIT NO. 31................523 Page 12 1 VIDEO OPERATOR: This is the start of 2 Tape 1 and we are on the record as of 9:13 a.m. 3 Would counsel please identify themselves for the 4 record? 5 MR. SMITH: Paul Smith for the 6 plaintiffs. 7 MS. ZETTLER: Nancy Zettler for the 8 plaintiffs. 9 MR. LORE: Steve Lore for Eli Lilly 10 and Company. 11 MS. SMITH: Beatrice Smith, Beaumont 12 Neurological Hospital. 13 MR. BROWN: Barton Brown for the 14 estate of Dr. Billingsley. 15 * * * * * * * * * * 16 COMES JOE WERNICKE, CALLED BY THE 17 PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, WAS 18 DEPOSED AND TESTIFIED AS FOLLOWS: 19 DIRECT EXAMINATION 20 BY MR. SMITH: 21 Q. Would you state your name, 22 please, sir? 23 A. Joe Wernicke. 24 Q. How old a man are you, sir? Page 13 1 A. Forty-six. 2 Q. And where do you live? 3 A. League City, Texas. 4 Q. And is League City, Texas near 5 any major cities? 6 A. Near Houston. 7 Q. Are you married? 8 A. Yes. 9 Q. And do you have children? 10 A. Yes. 11 Q. Does your wife work outside 12 the home? 13 A. Yes. 14 Q. Where does she work? 15 A. She has her own business. 16 Q. Doing what, sir? 17 A. It's a Jamboree franchise, a 18 parent/child play program that she owns and 19 operates. 20 Q. This is some child care kind 21 of -- 22 A. No, it's not child care, it's 23 a play program where parents bring their children 24 once a week and they have activities and Page 14 1 age-appropriate -- it's sort of 2 play-with-a-purpose kind of operation. It's a 3 national franchise, actually international. 4 Jamboree is the name of it. 5 Q. How long has she had that 6 activity? 7 A. Three years. 8 Q. Do you work, sir? 9 A. Yes. 10 Q. Where do you work? 11 A. A company called Cyberonics. 12 Q. Where is Cyberonics located? 13 A. In Webster, Texas. 14 Q. And is that also near Houston, 15 Texas? 16 A. Yes. 17 Q. What does Cyberonics do? 18 A. We're developing an 19 implantable stimulator for treatment of epilepsy. 20 Q. An implantable stimulator for 21 treatment of epilepsy? 22 A. That's correct. 23 Q. Where will that stimulator be 24 implanted, sir? Page 15 1 A. There are two parts of the 2 operation, there's a generator pacemaker-like 3 device that's implanted in the chest similar to a 4 heart pacemaker. The electrode is implanted on 5 the vagus nerve in the neck near where the 6 carotid pulse is felt, and those are then 7 tunneled under the skin and connected, and this 8 device then operates intermittently, 9 continuously, and by a mechanism that we don't 10 quite understand yet, interferes with seizures in 11 many patients. 12 Q. What is the name of that 13 device, sir? 14 A. We call it the NCP, neuro 15 cybernetic prosthesis system, NCP. 16 Q. Neuro -- 17 A. Neuro cybernetic -- 18 Q. Prosthesis? 19 A. -- prosthesis. 20 Q. Is that the only product 21 manufactured by Cyberonics? 22 A. The system -- there are 23 several components to the system: There's a 24 generator, the lead, we have software that is Page 16 1 used to program and change the programming, and a 2 communications programming wand that hooks into a 3 computer, and a tunneling tool used for the 4 operation to tunnel under the skin. All of those 5 things are manufactured, but that's all that we 6 do there. 7 Q. Is that device marketed now? 8 A. In Europe it's approved for 9 general distribution in the CE countries, and 10 it's under investigation in the United States. 11 Q. What countries in Europe have 12 approved this product for use? 13 A. All the CE countries, I think 14 there are twelve CE countries. There's now a 15 system called the CE marking, it's a process 16 similar to the FDA. There's a review of the 17 clinical and technical data, and once that's 18 approved by one, what is called a notified body, 19 that is -- once that approval is given, then you 20 have general distribution rights throughout the 21 European countries. So it can be marketed in all 22 of the twelve CE European community countries. 23 Q. What does CE stand for, sir? 24 A. Community European. It's sort Page 17 1 of a marking, it's like Underwriter Laboratories 2 marking, in that sense. It's a verification that 3 you have met and continue to meet the standards 4 as determined by this notified body, and there 5 are continual audits and updates. 6 Q. Where is that body centrally 7 located? 8 A. Well, there are many in 9 Europe. The one that we used was in Holland, but 10 one can use any of them from any of the countries 11 that basically -- with the harmonization of the 12 European community in the economic sense there's 13 been an effort to not have every country have its 14 own independent bodies that repeat everything. 15 So what they've decided to do is if a company 16 wants to import into Europe, they go through one 17 of these bodies that's agreed -- been agreed to 18 by all the governments, and that once that's 19 achieved, then it's as if Europe is one country 20 from a business point of view. 21 Q. Is this organization that 22 approves these products, is this for medical 23 devices only or does it include pharmaceutical 24 products, such as drugs? Page 18 1 A. I don't know what 2 pharmaceutical products. I know the CE marking 3 is on a lot of technical products, like 4 televisions, bicycles, cars. There are different 5 organizations and different subsets that approve 6 and test and evaluate a lot of parts. I don't 7 know whether this applies to pharmaceuticals, I 8 don't believe so. I'm not really aware of that 9 because I'm not involved in that right now. 10 Q. For this device to be approved 11 in the United States, obviously it has to be 12 approved by the Food and Drug Administration, is 13 that correct? 14 A. Correct, yes. 15 Q. And the entity within the 16 United States Federal Food and Drug 17 Administration would be the medical devices arm 18 of that group, would it not? 19 A. Correct. 20 Q. In other words, it would be a 21 different FDA group approving this NCP product 22 than it would be, say, approving Prozac for a 23 particular indication? 24 A. That's correct. Page 19 1 Q. Where is this NCP product in 2 the FDA approval process? 3 A. We have submitted what's 4 called a PMA, which is premarket authorization, 5 which is the equivalent of an NDA for a drug, and 6 that has been accepted and filed by the FDA and 7 is under review. 8 Q. When was that submitted? 9 A. In June of '93, I believe, was 10 the submission date. 11 Q. When did you join Cyberonics? 12 A. Early in 1990, I think it was 13 January, 1990. 14 Q. So you left Lilly and came 15 directly to Cyberonics? 16 A. Correct. 17 Q. Why did you leave Lilly? 18 A. Because I found out about this 19 company and -- initially I heard about it from 20 two people, the company president and one of the 21 venture capitalists came to Lilly basically to 22 talk about corporate partnerships, they were out 23 on the road talking to a number of big 24 pharmaceutical companies, and although I wasn't Page 20 1 in the device area of Lilly, I was in the 2 neurological central nervous system area so they 3 asked me to consult and help evaluate this. And 4 I heard their talk and they were very early in 5 their clinical trial development and I thought 6 this was really an incredibly novel concept. And 7 then a few weeks later I got a call from a search 8 agency and they asked me if perhaps I might want 9 to join them, and although I wasn't really 10 looking for anything, this was such an incredibly 11 novel idea where you could really take something 12 from the very beginning and have a major impact 13 on what it does for patients and there just 14 aren't that many opportunities like that in the 15 world, and that's what I chose to do. 16 Q. Okay, but Lilly had rejected 17 the overtures of Cyberonics to develop and market 18 that product? 19 A. I wouldn't say that, I'm not 20 sure that it ever got to that point. I was only 21 asked to help evaluate the science. I'm not at 22 all aware of any business discussions. It may 23 not have been offered, it may not have been 24 rejected, I'm just not aware of any discussions Page 21 1 that went on at that level. 2 Q. Was it your testimony, Doctor 3 Wernicke, that you were not in any way 4 dissatisfied with Eli Lilly and Company in 5 leaving Lilly? 6 A. That's correct, right. 7 Q. You joined Lilly in 1984, is 8 that right? 9 A. Yes. 10 Q. And when in 1984 did you join? 11 A. June, June of '84. 12 Q. And you had just completed 13 your medical training when you joined Lilly? 14 A. I had just finished my 15 fellowship in pediatric neurology, that's 16 correct. 17 Q. Were you Board certified in 18 neurology at the time you were at Lilly? 19 A. No. 20 Q. Are you now? 21 A. No. 22 Q. Is there any type of Board 23 certification in pediatric neurology? 24 A. Yes, there's a specialty, a Page 22 1 subspecialty certification that one can get. 2 Q. And did you obtain that? 3 A. No. 4 Q. Have you obtained that, sir? 5 A. No. 6 Q. Have you ever been involved in 7 private practice, Doctor Wernicke? 8 A. No -- well, let me qualify 9 that a little bit. In the university setting, I 10 was, but not traditionally private practice as 11 one thinks. 12 Q. Have you ever prescribed 13 Prozac, fluoxetine hydrochloride? 14 A. Yes. 15 Q. When? 16 A. I was a volunteer attending at 17 the pediatric neurology clinic at Indiana 18 University when I was at Lilly, and I remember a 19 young patient that had Tourette's syndrome, which 20 has a very large component of 21 obsessive/compulsive behavior, and there had been 22 reports in the literature that perhaps Prozac, 23 because it was already becoming clear that it was 24 effective for probably obsessive/compulsive Page 23 1 disorder, that it might be beneficial for such 2 patients. And nothing else really helped him, so 3 we tried that. 4 Q. And in how many patients did 5 you prescribe -- 6 A. That was the only one that I 7 can remember. 8 Q. One child? 9 A. Yes. 10 Q. Suffering from Tourette's 11 syndrome? 12 A. Yes. 13 Q. And at what dosage did you 14 prescribe Prozac to for that child? 15 A. As I remember, it was twenty 16 milligrams a day. 17 Q. And was the drug successful in 18 treating the symptoms of Tourette's syndrome? 19 A. Well, there are two components 20 of the symptoms, there's the obsessive mental 21 compulsive behavior, and then there are the 22 manifestations like the movements, and it did not 23 help the movements, but the obsessive component 24 did seem to respond. But it turned out that that Page 24 1 was not his major problem, his major problem were 2 the movements associated with it, so it was felt 3 that it wasn't really worth it. 4 Q. Did Prozac in any way increase 5 or aggravate the movement disorder aspect of this 6 child's problem? 7 A. Not as reported by the mother, 8 no. 9 Q. Well, did you continue to 10 observe that child? 11 A. Yes. 12 Q. And is that the only occasion 13 that you ever prescribed Prozac for any 14 individual? 15 A. I prescribed it for my wife 16 after she had cancer. 17 Q. All right. And was that for 18 depression related to her illness? 19 A. Yes. 20 Q. And for how long was your wife 21 on Prozac? 22 A. She's still on it, it's been 23 two years. 24 Q. How long has it been? Page 25 1 A. It's been two years. 2 Q. And at what dosage did you 3 prescribe it? 4 A. Twenty milligrams a day. 5 Q. Is that still the dosage? 6 A. Yes. 7 Q. Any other occasions in which 8 you prescribed Prozac? 9 A. The only other one is with my 10 secretary, she had been on it, but her doctor was 11 not available when she ran out of the 12 prescription so I just ordered the same 13 prescription. 14 Q. You just refilled it? 15 A. Just refilled it. So 16 technically I prescribed it, but not really in 17 the sense of treating her, just to get her to the 18 next appointment. 19 Q. And for what reason was your 20 secretary taking Prozac, Doctor Wernicke? 21 A. Depression. 22 Q. And do you remember the 23 dosage? 24 A. I believe it was twenty, it Page 26 1 was only one time, quite a long time ago, I don't 2 remember exactly. 3 Q. On any other occasions have 4 you prescribed Prozac? 5 A. I don't remember any other 6 occasions. 7 Q. You are not a psychiatrist? 8 A. True. 9 Q. And you have not been trained 10 as a psychiatrist either, have you, Doctor 11 Wernicke? 12 A. Well, in the neurology 13 training there's quite a large component of 14 psychiatry, both in the adult neurology and in 15 the residency and the fellowship. So I actually 16 spent quite a bit of time, both in medical 17 school, fellowship and residency, in psychiatry 18 training. 19 Q. Have you ever treated a 20 patient for a psychiatric condition? 21 A. Yes. When you say treated, I 22 think I want to clarify. All by myself, very 23 few. I spent a lot of time in the wards and in 24 the clinics at the universities where I trained, Page 27 1 and there I treated patients. 2 Q. I'm talking about as a 3 physician administering psychiatric care and 4 responsible for the psychiatric care of a patient 5 whose primary diagnosis is a psychiatric illness. 6 A. I would say no. 7 Q. When you joined Lilly, your 8 first job with them was a clinical research 9 physician or were you a medical monitor, at the 10 outset? 11 A. When I joined Lilly, the term 12 medical monitor had been sort of replaced by 13 research physician, and so my official title was 14 research physician. 15 Q. Whether or not the title had 16 been abandoned, did you in fact serve as the 17 medical monitor for the Prozac, fluoxetine 18 hydrochloride clinical trials at any time while 19 you were with Eli Lilly and Company? 20 A. Yes. 21 Q. For what period of time did 22 you do so, sir? 23 A. Sometime in 1984, and I don't 24 remember when that responsibility was officially Page 28 1 given over, it was for several years, but I don't 2 remember the end date that I served that specific 3 function. 4 Q. Well, you started in June of 5 1984. 6 A. Yes. 7 Q. So was it within thirty days 8 or -- 9 A. Yes. 10 Q. -- that you began the job as 11 medical monitor for the Prozac clinical trials? 12 A. Yes. I took that over within 13 the first months that I was there. 14 Q. All right. And how long did 15 you continue in that position? 16 A. That's what I don't remember 17 exactly because what happened was the whole 18 project got larger and larger as we started to 19 study other indications, there were more and more 20 studies, so several people were involved in that 21 and eventually I then went on completely to other 22 drugs. So there was a transition and I don't 23 remember the exact last day or month that I 24 served in that specific capacity. Page 29 1 Q. Let me see if I can help you a 2 little bit, then. Prozac was approved by the 3 United States Food and Drug Administration for 4 treatment in depressed individuals in December, 5 1987. Were you still the medical monitor in 6 charge of Prozac clinical research at that time? 7 A. There were a number of people 8 involved, even at that time. I was heavily 9 involved in the development and analysis of 10 Prozac. It's a little hard to say what the role 11 of medical monitor was because we weren't using 12 that term, we all had specific functions, 13 specific jobs, and sometimes several of us served 14 in one capacity. For instance, to review adverse 15 events, if one of us wasn't there, there was 16 always a back-up person. So there may have been 17 several people that did that job, it was not just 18 specifically assigned to one person and then on 19 the next day specifically to another person. So 20 it's a little hard to answer that in detail. 21 Q. Let's talk about organization 22 and conduct of the clinical trials in humans 23 prior to approval of Prozac for treatment in 24 depressed individuals. Were you, at any time Page 30 1 after you began with Lilly in June of '84, 2 responsible for all clinical trial work at Lilly 3 in connection with Prozac? 4 A. All the U.S. clinical trial 5 work. 6 Q. And for how long did you do 7 that? 8 A. It's -- I'm not quite sure of 9 the number of months, but I would estimate 10 approximately a year. 11 Q. And would that have been the 12 first year -- 13 A. Yes. 14 Q. -- for which you were involved 15 in Prozac? 16 A. Yes. 17 Q. So from 1984 until sometime in 18 probably the latter part of 1985, you were 19 responsible for all U.S. clinical trials in 20 connection with Prozac? 21 A. That's approximately correct. 22 Q. Can you tell me how many -- 23 approximately how many clinical trials were 24 ongoing in the United States during that period Page 31 1 of time, from mid-1984 to mid-1985? 2 A. We had a major depression 3 study that started soon after I joined Lilly. 4 That was followed by another large multi-center 5 blinded study. We had an obesity study that was 6 started at about that time that I was involved in 7 designing and setting up, but then that's when we 8 started to split off the Prozac -- fluoxetine 9 projects. 10 Q. Did you say a PC study? 11 A. Obesity, weight control. 12 Q. Obesity study. 13 A. I'm sorry. 14 Q. Okay. 15 A. So I was responsible in the 16 sense that I helped set up and design that study, 17 but when it was actually implemented, that was 18 split off and somebody else took that over. 19 Q. During that first year that 20 you were responsible for all United States 21 clinical trials on Prozac, was that all you did 22 at Lilly? 23 A. No. 24 Q. Did you work on other drugs? Page 32 1 A. At various times I had other 2 drugs within the scope of my responsibility. 3 Q. I'm talking about just that 4 first year that you were responsible for all 5 Prozac U.S. clinical trials. 6 A. It's very hard to remember in 7 1994 what I did in 1984 to '85, and to strictly 8 segment it that way because there were usually 9 not very sharp transitions. As new people came 10 on, we segmented the responsibilities, I took 11 over some other things, some of those then might 12 have gone away as other new people came on. So 13 it's very difficult to say with certainty from 14 this date to this date that's exactly what I did 15 and nothing else. 16 Q. For how long did you devote 17 the majority of your time to Prozac? 18 A. Most of the time that I was at 19 Lilly, actually. 20 Q. I would assume that in that 21 first year, when you were responsible for all 22 U.S. clinical trials, you were devoting maybe 23 ninety to ninety-five percent of your time to 24 Prozac? Page 33 1 A. That's approximately correct, 2 I would say. 3 Q. Can you point to any point in 4 time or give me any indicator where we might know 5 when the level of intensity of your work in 6 Prozac diminished from that ninety to ninety-five 7 percent? 8 A. It was sometime after 9 approval. 10 Q. All right. How long after 11 approval? 12 A. About the same time, say '88, 13 I started to be more and more involved in other -- 14 with other new drugs, and less directly with 15 fluoxetine. 16 Q. What other new drugs were you 17 involved with? 18 A. There's a totally novel 19 compound, and I think that's a proprietary secret 20 that I'm not sure, unless I check with Lilly 21 people, that I can discuss other drugs. 22 MR. LORE: Doctor, limit your answer 23 to only these drugs that you know that have been 24 marketed. Page 34 1 A. This was not a marketed drug, 2 so I don't want to talk about it. 3 Q. That's fine. Was it a CNS 4 active drug? 5 A. That one was. Marketed drugs, 6 I also did quite a bit of work on Pergolide or 7 marketed as Per-Max, for Parkinson's disease. 8 Q. Did you work on any other 9 antidepressants after Prozac was approved? 10 A. Only very peripherally, not 11 directly. 12 Q. When you say very 13 peripherally, give me some idea of what you did 14 in connection with other antidepressants that 15 Lilly was testing. 16 A. There was another drug that 17 was in some ways similar to fluoxetine but in 18 some ways different, where clinical trials had 19 been done and I was involved in the evaluation of 20 those clinical trials. And at some point, I 21 think for a fairly brief time, I was actually 22 what you would call the medical monitor for that 23 drug. And I was on project teams that evaluated 24 drugs very early in their development process at Page 35 1 the chemical stage, looking at animal data, to 2 help pick new candidates for drugs. 3 Q. Was that other drug, that 4 other antidepressant, ever marketed by Lilly? 5 A. Not that I know of. 6 Q. Was that other drug, that 7 other antidepressant, a serotonin specific 8 reuptake inhibitor? 9 A. No. 10 Q. Did it have serotonin reuptake 11 inhibition properties? 12 A. If it did, very minimally. 13 Q. How would it be characterized, 14 would it be characterized as a tricyclic or an 15 MAO or a combination, or do you know? 16 A. Neither of those, it was a 17 norepinephrine uptake inhibitor, not a specific 18 one. 19 Q. In any of the clinical trials 20 of that norepinephrine reuptake inhibitor, was 21 fluoxetine hydrochloride used as a comparator 22 drug? 23 A. Not while I was there, no. 24 Q. Do you know whether or not it Page 36 1 was used at any time? 2 A. I don't know, I have no 3 knowledge that it was. 4 Q. And by comparator drug, I'm 5 talking about a clinical trial where some of the 6 patients got this experimental study drug, the 7 nor -- say it. 8 MS. ZETTLER: Norepinephrine. 9 Q. Norepinephrine -- 10 A. NE. 11 Q. -- NE uptake inhibitor -- 12 reuptake inhibitor, as a study drug, and then 13 were given Prozac as a comparator drug to see 14 what the differing effects of the two medications 15 were on patients? 16 A. I don't know of any such 17 study. 18 Q. Do you know whether it was 19 ever proposed that Prozac be used as the 20 comparator drug for that medication? 21 A. I wouldn't say proposed, the 22 concept was discussed. 23 Q. All right. And who was 24 present during those discussions? Page 37 1 A. There were many discussions, 2 and I can't think of any specific discussion that 3 we had. 4 Q. Tell me, since there were many 5 discussions, who would have been present. 6 A. I know we had discussed it at 7 the project team level. Ray Fuller I know was 8 involved in those discussions, I believe Lou 9 Lemberger. Those are the only two that I 10 remember really talking about these nuances with -- 11 and Charles Beasley, but he had come on later. I 12 know we talked about that, too, because he was 13 monitoring that drug to use that term at that 14 time, so we talked about that concept. 15 Q. How about Doctor Leigh 16 Thompson, was he involved in any of these 17 discussions? 18 A. I don't remember specifically. 19 Q. How about Doctor Bob Zerbe? 20 A. Again, I don't remember 21 specific conversations. 22 Q. How about John Heiligenstein? 23 A. The same answer. 24 Q. Dan Masica? Page 38 1 A. I don't remember specific 2 conversations. 3 Q. Doctor Kotsanos? 4 A. Doctor Kotsanos, at that time -- 5 actually he came on quite a bit later and he was 6 more involved in epidemiology. So again, I don't 7 remember that, but I would be surprised if there 8 had been a conversation, certainly I don't think 9 I would have had it with him because he was 10 really just coming into the project at that time. 11 Q. How about Doctor David 12 Wheadon, was he there when you were there? 13 A. He was there when I was there, 14 uh-huh, yes. 15 Q. Was he involved in some of 16 these meetings where you were discussing the 17 concept of using Prozac as a comparator drug with 18 this new norepinephrine reuptake inhibitor that 19 was under investigation by Lilly as an 20 antidepressant? 21 A. I don't remember such a 22 meeting with him being present. 23 Q. Why was it decided not to use 24 Prozac as a comparator drug to this drug that was Page 39 1 being investigated that had a different mechanism 2 of action as an antidepressant medication? 3 A. It never really got that far 4 because the other drug, there were issues related 5 to that that made it more difficult to work with, 6 and enthusiasm for development of that drug was 7 somewhat dampened. 8 Q. Well, was that drug ever at 9 the stage where there were clinical trials 10 concerning the safety or efficacy of that 11 product? 12 MR. LORE: Paul, I'm going to object 13 to that. That question -- there's been a ruling 14 that we're not to get into or that you're not to 15 get into the substance about drugs that were not 16 marketed. 17 MR. SMITH: I'm not asking the 18 substance about drugs not marketed, I'm asking 19 what stage it was in -- 20 MR. LORE: Well -- 21 MR. SMITH: Wait a second, let me 22 finish. When there were discussions of using 23 Prozac as the comparator drug. If it was used as 24 a comparator -- potentially going to be used as a Page 40 1 comparator in animal studies, that's one thing, 2 but if it's in clinical trials of humans, that's 3 another thing. I'm not trying to get any 4 proprietary information, I'm just trying -- all 5 of my questions are directed to Prozac-related 6 issues. 7 MR. LORE: All right. Well, I 8 understood your question to be at what stage was 9 the drug at the point those discussions were 10 made, and that would imply as to how far Lilly 11 had gotten with that drug at that time. 12 MR. SMITH: So what? I'm not asking 13 for the name of the drug or what the results 14 were, I didn't even ask whether there was an IND 15 or NDA even submitted on the drug. My interest 16 simply is in knowing whether or not Prozac was 17 used as a comparator drug. He said it was 18 decided not to use it as a comparator drug. I 19 need to know whether or not it was ever -- the 20 comparator -- the drug under investigation was 21 ever used in humans, which would be relevant as 22 to potentially decisions why Prozac wasn't used 23 as a comparator drug. 24 MR. LORE: Is that your question? Page 41 1 MR. SMITH: Yes. 2 MR. LORE: Answer that, do you know if 3 it was ever used in humans? 4 THE WITNESS: Yes. 5 Q. (BY MR. SMITH) All right. 6 The norepinephrine experimental drug was 7 administered in clinical trials. 8 A. Yes. 9 Q. In humans. 10 A. Yes. 11 Q. And there were discussions 12 about whether or not to use Prozac as a 13 comparator drug -- 14 A. Yes. 15 Q. -- in those clinical trials, 16 is that right? 17 A. Yes. 18 Q. And the decision was made not 19 to use Prozac as a comparator drug in those 20 clinical trials, is that right? 21 A. The decision was made not to 22 use any comparator drug because the studies that 23 had been done were placebo controlled. 24 Q. All right. Page 42 1 A. And at least when I was there 2 there were no other studies started, so there was 3 really no decision to be made about a comparator 4 drug of any type. 5 Q. Okay. Did the 6 placebo-controlled trials not show efficacy? 7 MR. LORE: I'm going to object to 8 that, that clearly goes to the experimental drug, 9 Paul. 10 MR. SMITH: Well, I'm not asking what 11 it is. 12 MR. LORE: No, but you're asking 13 whether -- that question, don't answer that 14 question. 15 MR. SMITH: All right. 16 Q. (BY MR. SMITH) There were 17 many -- there were several drugs used as 18 comparator drugs in the Prozac clinical trials, 19 were there not? 20 A. Yes. 21 Q. And that's not unusual in a 22 clinical trial process to employ comparator drugs 23 to measure the efficacy and safety of the 24 investigated drug, not only versus a placebo, Page 43 1 which is no drug, but versus a comparator drug, 2 which is theoretically a drug that also has 3 antidepressant properties, correct? 4 A. Correct. 5 Q. Do you know of any instances 6 while you were at Lilly when Prozac was in fact 7 used as a comparator drug for any Lilly clinical 8 trials of any Lilly investigated drugs? 9 A. I'm not aware of any such 10 incident. 11 Q. Do you know why Prozac was 12 never used as a comparator drug for any Lilly 13 clinical trials on other drugs under 14 investigation by Lilly? 15 A. Well, the only other one that 16 would even be a candidate is this norepinephrine 17 uptake inhibitor we talked about since there was 18 no other antidepressant. But the reason one does 19 a comparator study is usually against an older 20 drug that's known in the medical community. The 21 purpose of doing a comparator study is to give 22 physicians information how this new drug compares 23 to what they're used to. 24 Q. All right. Well, are you Page 44 1 saying that by the time you left in 1990, that 2 Prozac wasn't known within the medical community 3 as a marketed antidepressant medication? 4 A. It was certainly by that time, 5 but as certainly in drugs that I was involved 6 with there were no antidepressants far enough 7 along in the process to even consider that that 8 was a viable option. There are a lot of other 9 reasons why one might not want to do that. 10 Q. There weren't any other drugs, 11 other than this one antidepressant that Lilly was 12 studying? 13 A. That other antidepressant was, 14 I would say, in the background at that time. 15 Q. Well, it was being used in 16 clinical trials. 17 A. It had been and was still 18 being used in extension, but there were no new 19 studies that I was aware of. 20 Q. And do you know of any 21 instances, Doctor Wernicke, where Prozac was used 22 as a comparator drug of any other antidepressant 23 medications marketed by other or investigated by 24 other pharmaceutical firms? Page 45 1 A. I know that requests were 2 made, and I believe I've heard of a study against 3 Zoloft, marketed by Pfizer. I know there was 4 discussion of them wanting to use it as a 5 comparison and I vaguely remember seeing 6 something about that, but I don't know the 7 details. 8 Q. Do you remember seeing a study 9 that was actually done or do you remember some 10 type of discussions with Pfizer in connection 11 with supplying Prozac? 12 A. All I heard was that Pfizer 13 was interested in using Prozac as a comparator, 14 and I never saw a protocol and I don't know if it 15 was actually ever done but I had heard that there 16 were discussions along that line. 17 Q. For those who might not know's 18 benefit, Zoloft is another antidepressant -- 19 A. Yes. 20 Q. -- that is a cousin of Prozac 21 in that it is a specific serotonin reuptake 22 inhibitor. 23 A. Yes. 24 Q. Tell me, Doctor Wernicke, when Page 46 1 you first learned while you were at Lilly that 2 there might be some association with Prozac and 3 suicidality or violent aggressive behavior. 4 A. When you say there might be 5 some association, that's a presumption, I'm not 6 sure that I ever learned of that because that 7 basically is not a fact. The question was asked -- 8 Q. Well, my question was very 9 specific. When was it that you first learned 10 that there was some concern or some issue being 11 raised concerning whether or not Prozac usage 12 might be associated with suicidality or violent 13 aggressive behavior? 14 A. Those are two very separate 15 and distinct entities. 16 Q. Why do you say that? 17 A. Well, because a person can 18 commit suicide very quietly in their own garage 19 and it has nothing to do with violence, except to 20 themselves, or aggressive behavior. 21 Q. Let's get -- 22 A. Let me finish that because I 23 think you're fundamentally very confused, and I 24 want to make sure -- Page 47 1 Q. I doubt it, but go ahead. 2 A. When you're talking about 3 aggressive behavior, that may not have anything 4 to do with suicide. So yes, in some instances 5 there can be an overlap, but certainly -- we just 6 had a case here where twelve young boys murdered 7 an eighty-four year old woman to steal her car. 8 They certainly weren't suicidal. 9 Q. Were they taking Prozac? 10 A. Not that I know of, I don't 11 know. But there are many people that commit 12 suicide by taking sleeping pills, and that 13 certainly is not aggressive. So when you throw 14 all of these into one sort of large fuzzy basket, 15 it makes it really impossible to talk about. 16 Q. Let's get this straight, 17 Doctor Wernicke, or let me see if I understand 18 something. You're a neurologist, are you not, by 19 training? 20 A. Yes. 21 Q. And you've never been in the 22 private practice of medicine. 23 A. Except in the university 24 setting. Page 48 1 Q. And that's while you were in 2 school. 3 A. Correct. 4 Q. All right. And you've never 5 administered Prozac to patients for treatment of 6 depression. 7 A. Except the instances that I've -- 8 Q. And neither one of those 9 individuals was a patient of yours, were they? 10 A. In the sense that I prescribed 11 their medication, I would say that they were. 12 Q. You weren't responsible for 13 their regular ongoing medical care, were you, 14 Doctor Wernicke? 15 A. For my wife, I was. 16 Q. Well, you weren't treating her 17 cancer, were you? 18 A. No. I was talking about the 19 medical care related to the fluoxetine, not the 20 cancer, that's correct. 21 Q. If we asked your wife who her 22 doctor was, she probably wouldn't list you, would 23 she? 24 A. That's correct. Page 49 1 Q. In fact, she'd say my husband 2 is a physician but he doesn't practice medicine, 3 wouldn't she? 4 A. An That would be correct. 5 Q. Not only are you not 6 practicing medicine, you're not practicing 7 psychiatry either, are you? 8 A. That's correct. 9 Q. And you're not currently 10 keeping yourself abreast of psychiatric 11 literature, are you? 12 A. That would be correct. 13 Q. And you're, in fact, not 14 dealing with pharmaceuticals at this time, are 15 you? 16 A. That's correct. 17 Q. You're dealing with medical 18 devices. 19 A. That's correct. 20 Q. And your interest is separate 21 and apart from psychiatry at this time. 22 A. Yes. 23 Q. All right. Now, when you say 24 that suicide and violent aggressive behavior are Page 50 1 not related, you're not rendering a psychiatric 2 expert opinion, are you? 3 A. No, and I never claimed that I 4 was. 5 Q. Well, you said it, you said 6 that I was fuzzy, and that I was incorrect in 7 relating suicide and violent aggressive behavior, 8 didn't you? 9 A. In as far as my understanding 10 of these behaviors and from what I learned and 11 saw, I would say yes, that's a fuzzy 12 relationship. 13 Q. Are you saying, Doctor 14 Wernicke, you've never heard of the concept that 15 the -- from a psychological, psychiatric 16 standpoint, that there is a relationship between 17 violent aggressive behavior and suicidality? 18 A. When you say that have I heard 19 of that relationship, I have heard that a link 20 has been proposed, that's true. 21 Q. And in fact the thought was, 22 at the time Prozac was under investigation, was 23 is that Prozac might reduce suicidality and might 24 reduce violent aggressive behavior because each Page 51 1 was related theoretically to actions of the 2 serotonin system, correct? 3 A. No, not correct. 4 Q. Incorrect? 5 A. Incorrect. It was thought 6 that it would decrease suicidal behavior, because 7 suicidal behavior is a key element of depression. 8 If one looks at the statistical manual for 9 depression and for major depressive disorders, 10 suicide is a clear feature of that, violent 11 aggressive behavior is not. 12 Q. All right. 13 A. So there was never any 14 supposition that I remember that Prozac would 15 decrease violent aggressive behavior because it's 16 a totally different entity, as per the 17 psychiatric community, not in my opinion. 18 Q. So it's your understanding 19 that suicidality is an element of depression? 20 A. Yes. 21 Q. And that you could expect to 22 see some element of suicidality in depressed 23 individuals, is that right? 24 A. Yes. Page 52 1 Q. But violent aggressive 2 behavior is not an element of depression, is that 3 right? 4 A. Not to my knowledge. 5 Q. And you would not expect to 6 see violent aggressive behavior in an individual 7 who is being treated for depression, is that 8 correct? 9 A. Not as part of that disease of 10 depression. 11 Q. All right. So you couldn't 12 say that an individual who committed a violent 13 aggressive act was doing so by virtue of the 14 underlying depressive medical illness for which 15 they suffer? 16 A. I would not make the 17 association between those two. Now that -- 18 Q. Are you saying then by virtue 19 of that, that you would not expect to see 20 instances of aggression, agitation, hostility, in 21 patients who were suffering from depression? 22 A. Well, agitation I would expect 23 to see because there is a form of major 24 depression that's called agitated depression. Page 53 1 Q. How about aggression and 2 hostility, would you expect to see aggression and 3 hostility in the clinical picture of depressed 4 individuals? 5 A. In the pure form of major 6 depressive disorder, that is not a known feature 7 of the disease. 8 Q. All right. How about 9 irritability, is that a known form in the pure 10 form of depression? 11 A. Yes. 12 Q. How about anger, are depressed 13 individuals normally angered as part of their 14 disease process? 15 A. Some may be, that may be a 16 manifestation. 17 Q. Would you expect to see a 18 percentage of depressed individuals becoming 19 angry during the Prozac clinical trials? 20 A. Anger -- it's a very -- well, 21 it's not a vague term, but it's a vague concept, 22 and in the agitated form of the -- 23 Q. Go ahead. 24 A. Anger can be a manifestation Page 54 1 or can be an expression of the agitation, if 2 patients have agitated depression, they may 3 appear angry. So anger isn't really a medical 4 entity, so I have difficulty dealing with that on 5 that level. 6 Q. All right. Well, to get back 7 to the original premise, Doctor Wernicke, could 8 it be said that violent aggressive behavior and 9 suicidality are linked to the serotonin system by 10 virtue of the fact that the serotonin system has 11 a part in impulse control in individuals, 12 impulsivity? 13 A. Impulsivity is not a 14 diagnostic entity, the closest relationship is 15 obsessive/compulsive disorder, if one wants to 16 make that relationship. So to make, first, a 17 link from serotonin impulsivity to violent 18 aggressive behavior, I'm not aware that those 19 links have been established on a scientific 20 basis. 21 Q. Would you agree that violent 22 aggressive behavior and suicidality have similar 23 biological markers? 24 A. I'm not aware of that. Page 55 1 Q. Would -- did you ever have any 2 conversations with Doctor Charles Beasley about 3 that? 4 A. I don't remember specifically 5 talking about that. 6 Q. Who would you consider more 7 knowledgable about that, yourself or Doctor 8 Charles Beasley, since he's a psychiatrist? 9 A. Doctor Beasley. 10 Q. And on this entire issue of 11 whether or not suicidality and violent aggressive 12 behavior, would you defer to somebody who is a 13 psychiatrist, who has had training and specific 14 emphasis and who's kept abreast of the literature 15 in this area? 16 A. Yes. 17 Q. Back to the very original 18 question, and I'll break it down to make it more 19 suitable. When was it that you first learned, 20 Doctor Wernicke, that there was questions being 21 raised concerning whether or not Prozac was 22 related to suicidality? 23 A. I first became aware of 24 questions related to suicides that had occurred Page 56 1 in the fluoxetine trials sometime in 1984 in 2 relationship to the questions from the German 3 government, but there was no allegation, that I 4 know, that there was a direct causal link. 5 Q. That wasn't my question, my 6 question was when was it first raised as a 7 concern? 8 A. A question -- I would say 9 there was a question about it. Whether people 10 are concerned is in their mind. What we had was 11 the question posed to us. 12 Q. Doctor Wernicke, let me get 13 this clear with you, okay, so it will make it 14 easier for you. I believe that Prozac causes 15 individuals to become suicidal and I believe that 16 Prozac causes individuals to become violent 17 aggressive and homicidal, all right, that's my 18 belief. I'm not a physician, but I'm a lawyer 19 representing a lot of people who have had this 20 tragic situation in their lives and in the lives 21 of their loved ones, all right. I understand 22 that you're a former employee of Lilly and that 23 you disagree with that, okay, and I'm not trying 24 to trick you in getting you to say that, all Page 57 1 right. So when I say the question was being 2 raised, I'm simply asking that question in the 3 most general term, all right, I'm not trying to 4 trick you, okay? 5 A. I understand that, but if you 6 start with a premise, followed with a question -- 7 Q. I'm not starting with that 8 premise. 9 A. Just make sure the premise is 10 correct because then I can't get to the question. 11 Q. That's the heart of these 12 lawsuits, is whether or not there is a causal 13 relationship between Prozac and suicidality in 14 some individuals, Prozac and violent aggressive 15 behavior in some individuals. That's what a jury 16 is going to decide, all right. But I'm not 17 trying to trick you into saying that there was at 18 some point some definite proof that you were 19 aware of that you didn't tell somebody about or 20 something of that nature, all right? 21 A. I understand. I can answer 22 the questions truthfully and honestly. 23 Q. Well, I wanted to explain to 24 you carefully that I'm not trying to trick you on Page 58 1 this, all right? 2 A. I hear what you said. 3 Q. I notice that you speak with 4 an accent that's not indigenous to Indianapolis 5 or Houston. 6 A. True. 7 Q. Is English your native 8 language? 9 A. No, it's not. 10 Q. What is your native language? 11 A. German. 12 Q. If I ask you any questions -- 13 since German is not my native language, I'll 14 continue to ask you questions in English. If I 15 ask you any questions that you don't understand 16 or that you need for me to repeat, feel free to 17 ask me, Doctor Wernicke. 18 A. Thank you. 19 MR. SMITH: Why don't we take a quick 20 break. 21 (A SHORT RECESS WAS TAKEN.) 22 Q. (BY MR. SMITH) Were you born 23 in Germany, Doctor Wernicke? 24 A. Yes. Page 59 1 Q. All right. How long did you 2 live in Germany? 3 A. Until I was nine years old. 4 Q. Then you moved to the United 5 States? 6 A. Correct. 7 Q. And your parents spoke German, 8 I assume? 9 A. Yes. 10 Q. And continued to speak German 11 in the house, at least, after you moved to the 12 United States? 13 A. Yes. 14 Q. Have you been back to Germany 15 to visit family or friends? 16 A. Yes. 17 Q. Since 1984? 18 A. Yes. 19 Q. When was the last time you 20 were in Germany? 21 A. A few months ago. 22 Q. Do you still have a number of 23 family and friends in Germany? 24 A. Yes, my parents have actually Page 60 1 moved back to Berlin, and I have a brother and 2 his wife that live in Berlin. 3 Q. And have they always lived in 4 Berlin? 5 A. No, he was born in the United 6 States, but through circumstance he just happened 7 to wind up there and decided to stay there. 8 Q. Have you become a United 9 States citizen or are you -- 10 A. I'm United States -- 11 Q. All right. Did you ever go to 12 Germany when you were employed by Lilly? 13 A. Yes. 14 Q. When? 15 A. I don't remember the year. 16 There was a psychiatric conference, an 17 international medical conference, in Munich, but 18 I don't remember exactly the year. 19 Q. Did you participate in that 20 conference? 21 A. Not really. I attended 22 lectures and symposia, but I didn't really 23 participate. 24 Q. Were you an attendee to that Page 61 1 conference? 2 A. Yes. 3 Q. Were you there with other 4 Lilly employees? 5 A. There were other Lilly 6 employees there, they had an exhibit, and I spent 7 some time at the exhibit answering questions. 8 Q. Was that a Fluctin exhibit? 9 A. I don't remember because I'm 10 not sure whether that had been approved in 11 Germany at that time. As far as best as I can 12 recollect, no, approval had not been granted, and 13 so that was not specifically about Prozac, but I 14 have a fuzzy memory of the exact details. 15 Q. Fluctin is Prozac in Germany, 16 is it not? 17 A. That was the intent when I was 18 at Lilly, now I don't know whether now they're 19 using that trade name or not, but that's how we 20 referred to it at that time. 21 Q. But it's exactly -- Fluctin in 22 Germany -- at the time it was Fluctin in Germany, 23 it was exactly the same chemical compound as 24 Prozac is in the United States? Page 62 1 A. Yes. 2 Q. And Fluctin in Germany is 3 manufactured by Eli Lilly and Company or one of 4 its subsidiaries, is it not? 5 A. Yes. 6 Q. So this psychiatric conference 7 in Munich that you attended would have been 8 something prior to Fluctin being approved in 9 Germany, which was December, 1989, correct? 10 A. I believe so, I don't remember 11 the exact sequence. 12 Q. Well, you were still employed 13 by Lilly when fluoxetine hydrochloride was 14 approved for use in Germany, were you not? 15 A. You said it was in December of 16 1989? 17 Q. Yes. 18 A. That would have been just 19 about the time I left. 20 Q. All right. When you were in 21 Munich or in Germany for this conference, did you 22 speak with any members of the BGA? 23 A. No. 24 Q. Do you know what I mean when I Page 63 1 refer to the BGA in Germany? 2 A. Yes. 3 Q. Explain what your 4 understanding is of the BGA? 5 A. My understanding is that it's 6 the equivalent of the FDA, it stands for Bundes 7 Gesundheits Amt. 8 Q. And when you were in Germany, 9 did you ever speak with any members of Commission 10 A? 11 A. No. 12 Q. Explain to the jury what 13 Commission A is, Doctor Wernicke. 14 A. I never actually heard that 15 term, so by definition I did not speak to them 16 since I did not know who they were. That doesn't 17 have any recollection for me as to what 18 Commission A is. 19 Q. Well, are you familiar that 20 the BGA is a little different from the FDA in 21 approval of drugs in that the BGA always refers 22 drugs under application for marketing in Germany 23 to a commission comprised of medical doctors or 24 specialists that review and approve an Page 64 1 application for a medication for the BGA? 2 A. I'm not aware of that level of 3 detail of their evaluation and approval process, 4 but I do know that in Europe in general that 5 approach is taken, that there's an external 6 commission that then advises the government. But 7 I'm not aware of the details, country by country, 8 of exactly who does what. 9 Q. When you were in Munich or in 10 Germany, which is just one occasion, am I right? 11 A. It's the one occasion I can 12 remember. There may have been another 13 psychiatric conference, but it would have been in 14 the same scope. I don't remember specifically 15 while I was at Lilly of being at any other 16 gatherings. 17 Q. Well, whether or not it was 18 one or two occasions, did you ever speak with any 19 European or German consultants while you were in 20 Germany, hired by Lilly or related to Lilly, to 21 advise Lilly concerning registration of Fluctin 22 in Germany? 23 A. No. 24 Q. You're sure about that? Page 65 1 A. I'm quite certain about that. 2 At least if I did, I was not aware that they were 3 acting in the capacity of a consultant. I did 4 talk to a number of psychiatrists that were doing 5 studies. Now if one of them later became a 6 consultant, that's possible, but not in that role 7 in that context, I'm quite certain of that. 8 Q. All right. You are certain, 9 though, that you did, while you were in Germany, 10 talk with German psychiatrists or European 11 psychiatrists who were doing fluoxetine 12 hydrochloride studies in Germany or in Europe 13 somewhere, is that right? 14 A. Yes. 15 Q. Who were they, please, sir? 16 A. There was a Doctor Laakman, 17 L-A-A-K-M-A-N. 18 Q. L-A-A? 19 A. Yes, two As, K-M-A-N, Laakman. 20 Q. What was Doctor Laakman's 21 first name? 22 A. I don't remember. It might 23 come to me, but I don't remember at this point. 24 I believe it was Herrmann, but I'm not exactly Page 66 1 sure about that. 2 Q. Doctor Herman Laakman or was 3 there another doctor by the name of Herrmann that 4 you talked with? 5 A. I never talked to a Doctor 6 Herrmann. 7 Q. How do you know that? 8 A. Not that I remember. 9 Q. All right. Have you heard 10 Doctor Herrmann's name before? 11 A. I've heard that name, but I'm 12 not quite sure of the details of what context. I 13 never talked to a Doctor Herrmann. 14 Q. Well, have you reviewed any 15 documents in preparation for your deposition 16 today, Doctor Wernicke? 17 A. I read over the transcript of 18 my previous deposition. 19 Q. All right. Have you reviewed 20 any other documents in preparation for your 21 deposition here today? 22 A. No. 23 Q. Have you talked with Mr. Lore 24 concerning your deposition here today? Page 67 1 A. Yes. 2 Q. When did you talk with Mr. 3 Lore? 4 A. We had a meeting four to six 5 weeks ago, the last month and a half or so. 6 Q. Where was that meeting? 7 A. Where? Here in Houston. 8 Q. What was the subject of that 9 meeting? 10 MR. LORE: I'm going to object to 11 that, Paul. The judge has ruled that our 12 conversations are protected. 13 MS. ZETTLER: He has not. 14 MR. LORE: Yes, he has. 15 MS. ZETTLER: Which judge? 16 MR. LORE: Judge Potter. 17 MS. ZETTLER: No, he's not. 18 MR. LORE: What was his ruling? We 19 need to call him, then. 20 MS. ZETTLER: Let's call him because 21 he has not ruled on any issue related to that in 22 this case, that's absolutely untrue, and unless 23 you can produce some order you claim says that, 24 we'll call the judge right now. Page 68 1 MR. LORE: I recall you raising this 2 very issue in a deposition, the deposition was 3 suspended and you never raised it again. I 4 assumed that you called Judge Potter at that 5 point. 6 MS. ZETTLER: Well, you're making the 7 wrong assumption, we've never called Judge Potter 8 about this issue. 9 MR. LORE: Well, I'll instruct you not 10 to answer that question, and we can take it up 11 before him again, but it's my understanding that 12 that is something that's been disallowed. He is -- 13 I am representing him as an attorney, my 14 discussion with him is privileged. 15 Q. (BY MR. SMITH) Have you paid 16 Mr. Lore or Freeman and Hawkins to represent you 17 in this case -- 18 A. No. 19 Q. -- Doctor Wernicke? 20 A. No, I have not. 21 Q. Does Freeman and Hawkins or 22 Mr. Lore represent your current employer? 23 A. No, not to my knowledge. 24 Q. Have you signed any type of Page 69 1 contract with Mr. Lore or Freeman and Hawkins? 2 A. No. 3 Q. Have you entered in any type 4 of attorney/client relationship, have you asked 5 him for legal advice? 6 A. You asked two questions. I'm 7 not an attorney, so I'm not quite sure what the 8 scope of attorney/client relationship includes, 9 and yes, I have asked him for advice. 10 Q. All right. Advice in 11 connection with this litigation? 12 A. I asked him for general advice 13 as to how one should conduct one's self at a 14 deposition since I'm not as experienced in that. 15 Q. Did you have some concern 16 about how you should conduct yourself here, 17 Doctor Wernicke? 18 A. No. 19 Q. Did you call Mr. Lore and ask 20 him to come to Houston and meet with you to 21 consult with you on how you should act in a 22 deposition? 23 A. No. 24 Q. Or did he contact you? Page 70 1 A. He contacted me. 2 Q. And you've never heard of Mr. 3 Lore before he contacted you, did you? That may 4 be embarrassing to Mr. Lore, but you didn't know 5 Mr. Lore before he contacted you, did you? 6 A. About this deposition? 7 Q. Yes, or about anything. 8 A. There was a prior deposition 9 in March and April, and Mr. Lore was involved in 10 that, so yes, I had heard of him before this one. 11 Q. Yes, but before that prior 12 deposition? 13 A. Before that whole process, I 14 did not know him. 15 Q. All right. And Mr. Lore had 16 to identify himself when he first called you, 17 didn't he? 18 A. I don't believe he called me 19 first, I believe a Lilly lawyer called me first 20 and said Mr. Lore would be involved, so he was 21 introduced to me. 22 Q. Okay. So Mr. Lore is somebody 23 that was -- that is representing Eli Lilly and 24 Company is your understanding? Page 71 1 A. That's my understanding. 2 Q. And did you know that you had 3 been listed as an expert witness by Lilly? 4 A. There was some discussion of 5 that, but again, I'm not really that aware of 6 what the implication of all that is. 7 Q. Well, the implication is that 8 since they've listed you as an expert witness, 9 Doctor Wernicke, that we can inquire of you as to 10 what discussions you've had with Mr. Lore, all 11 right? 12 A. That's between you and Mr. 13 Lore to decide, and the judge. 14 Q. So I'm going to ask you again, 15 what discussions, when Mr. Lore and you met in 16 Houston a few weeks ago, did you all have? 17 MR. LORE: And I'm going to object to 18 that question on the basis that if he is my 19 expert, then what I have discussed with him is 20 attorney/work product. I don't know that he's 21 been listed as an expert -- 22 MR. SMITH: He has. 23 MR. LORE: -- in this case. 24 MR. SMITH: And by virtue of you Page 72 1 listing him as an expert, what your work product 2 might have been ceases to be a work product, as 3 you well know, Mr. Lore. 4 MR. LORE: Well, I'm going to instruct 5 him not to answer that question. 6 MR. SMITH: However good or bad it 7 might have been, that product, it ceases. 8 MR. LORE: Well, that will, I guess, 9 present itself at some point. 10 Q. (BY MR. SMITH) I'll ask you 11 again for the record, what conversations have you 12 had with Mr. Lore in connection with your 13 testimony? 14 MR. LORE: And I'll instruct you not 15 to answer the question. 16 MR. SMITH: All right. 17 MS. ZETTLER: Are you going to follow 18 Mr. Lore's instruction, Doctor Wernicke? 19 THE WITNESS: Yes. 20 MS. ZETTLER: Certify it. 21 (QUESTION CERTIFIED.) 22 Q. (BY MR. SMITH) What type of 23 studies was Doctor Laakman doing? 24 A. Depression studies. Page 73 1 Q. And what was your conversation 2 with Doctor Laakman? 3 A. I don't remember details. We 4 had several discussions about depression and use 5 of medications, but that's fairly general, I 6 don't remember specific details that many years 7 ago. 8 Q. Well, did the issue of Prozac 9 and suicidality arise during any of those 10 discussions? 11 A. Not that I remember. 12 Q. Was this after the question 13 had been raised by the BGA that you had this 14 meeting with Doctor Laakman? 15 A. It was after we dealt with the 16 questions from the BGA related to that. 17 Q. So, again, I'll ask you, were 18 your discussions with -- did your discussions 19 with Doctor Laakman include the issue of Prozac 20 and suicidality? 21 A. I honestly don't remember 22 whether we discussed that particular point. 23 Q. Where does Doctor Laakman 24 reside? Page 74 1 A. Somewhere in Germany, that's 2 all I know, I don't remember. I didn't go to his 3 office, we met at some of these conferences, so I 4 don't really know. 5 Q. What was the purpose of your 6 meeting with him, Doctor Wernicke? 7 A. He was going to be one of our 8 investigators, so I always tried to meet all the 9 investigators. 10 Q. Were you resonsible for 11 European clinical trials at that time? 12 A. No, not directly, not in the 13 sense of managing the study on a day-to-day 14 basis. 15 Q. Why were you in Germany 16 anyway? 17 A. To attend a scientific 18 conference to find out what people's reaction was 19 to fluoxetine, to learn about other drugs, to 20 learn more about psychiatry in general, to meet 21 there investigators and potential investigators, 22 to help answer questions at the exhibit booth. 23 So I had a number of roles. 24 Q. Who else from Lilly Page 75 1 accompanied you -- from Lilly in the United 2 States accompanied you to this conference? 3 A. I don't remember anybody at 4 that conference accompanying me from Lilly. 5 Q. Did anybody meet you there 6 from Lilly in the United States? Surely you 7 weren't the only individual from Lilly in the 8 United States present at the meeting, were you? 9 A. I believe Ray Fuller was at 10 the meeting -- 11 Q. All right. 12 A. -- at the scientific portion 13 of the meeting, but I'm not absolutely certain 14 about that. I vaguely remember seeing him there. 15 Q. Since it was a psychiatric 16 conference, were any of the U.S. Lilly 17 psychiatrists there? 18 A. I don't know. 19 Q. Like Doctor Beasley? 20 A. I'm not sure Doctor Beasley 21 was at Lilly at that time. 22 Q. How about Doctor 23 Heiligenstein? 24 A. I know he was not there. I Page 76 1 believe this preceded them really being involved. 2 I only remember myself being there from the 3 medical group. 4 Q. So Doctor Zerbe wasn't there? 5 A. Not that I remember. 6 Q. Doctor Weinstein wasn't there? 7 A. I don't remember seeing him, 8 and I certainly didn't go with him. 9 Q. Did you take your family? 10 A. No. 11 Q. How long was the conference? 12 A. Several days, I don't remember 13 exactly. 14 Q. How long were you in Germany? 15 A. Several days. I basically 16 went for that conference. 17 Q. Were you there long enough to 18 visit with family members that you hadn't seen? 19 A. I have been in Germany a 20 number of times and I can't say for sure that I 21 did at that time, I just don't remember. This 22 was quite a while ago. 23 Q. And Doctor Laakman was running 24 depression studies, is that right? Page 77 1 A. In general, with a number of 2 drugs. I don't know the time relationship, 3 whether he had started the fluoxetine studies or 4 whether we were just talking about it. He did do 5 fluoxetine comparator studies. 6 Q. He did fluoxetine comparator 7 studies? 8 A. Amitriptyline, as I remember. 9 Q. And did he have a placebo arm 10 in his study? 11 A. No. 12 Q. Do you know whether or not 13 there was any suicides or suicide attempts in his 14 study? 15 A. I don't remember about his 16 study in particular. 17 Q. Was there any other goal of 18 this study other than to study Prozac in 19 individuals with major depressive disorder? 20 A. I believe not, that was -- 21 Q. For instance, like a geriatric 22 study or a dose-ranging study or something of 23 that nature? 24 A. I believe, and I'm not a Page 78 1 hundred percent sure, but I believe his study was 2 focused more on more severely depressed patients, 3 and we did an inpatient study and I believe he 4 was involved in that, but again, I can't be one 5 hundred percent certain. 6 Q. Where were his patients 7 hospitalized? 8 A. I don't know. 9 Q. All right. What other 10 psychiatrists did you meet with at this meeting? 11 A. I remember talking with Doctor 12 Stuart Montgomery from the UK. 13 Q. All right. Had Doctor 14 Montgomery done any studies on Prozac at that 15 time? 16 A. I don't believe so. 17 Q. Go ahead. 18 A. I don't remember him doing it. 19 I know he did one, but I believe that was later. 20 Q. All right. Were you familiar 21 with the study he did later? 22 A. Yes. 23 Q. And what study was that? 24 A. His concept was, in fact, that Page 79 1 drugs like Prozac, serotonin uptake inhibitors, 2 would decrease suicidality. And he did a study 3 looking at long-term fluoxetine and I don't 4 remember what the comparator was, looking at the 5 suicide rates -- or at suicide attempt rates 6 throughout that study, and I never saw the 7 complete study because I left around that time, 8 but I had heard that in fact the suicide rate in -- 9 or an attempt rate in the fluoxetine group was 10 about half that of the comparator. 11 Q. Do you know what, Doctor 12 Wernicke, you're getting some real bad 13 information. 14 A. Well, that may be, I'm just 15 telling you what I have heard. 16 Q. That's absolutely wrong. In 17 fact, the suicide rate was equal to or greater 18 than the placebo. In fact, the placebo arm did 19 better than Prozac, did you know that? 20 A. I did not know that. 21 MR. LORE: I object to the form of the 22 question. Whatever the facts are the facts, 23 Paul. He just told you what he recalled. 24 MR. SMITH: We're going to ask him a Page 80 1 little more about that. 2 Q. (BY MR. SMITH) Where did you 3 hear that Prozac did better in Doctor 4 Montgomery's suicide prophylaxis study? 5 A. I don't remember where I heard 6 that. It was right at about the time I was 7 leaving and it was preliminary information, 8 somebody said oh, I heard that that's what they 9 were finding, and that was about the extent of 10 it. That's why I'm cautious about the study 11 because I've never read the study and any 12 conclusion that anybody tells me about the study, 13 I would take with caution until I had seen the 14 study and evaluated it myself. 15 Q. You didn't seem to have any 16 problems in telling me, volunteering to me that 17 Doctor Montgomery's study demonstrated that there 18 were about half the suicide attempts of the 19 people in Prozac. 20 MR. LORE: I object to the question, 21 he didn't volunteer, you asked him the question, 22 Paul. 23 A. You asked what the result was, 24 and I said this is what I had heard. Page 81 1 Q. All right. Who did you hear 2 that from, sir? 3 A. I don't remember that. 4 Q. Was it somebody at Lilly? 5 A. Well, if I knew where it was, 6 I would know who it was. It was when I was at 7 Lilly, but I don't remember the context of how I 8 heard that. 9 Q. Did you read it in some type 10 of report? 11 A. No, no. I remember just 12 hearing this, and I thought well, that seems 13 interesting, and that's the last I heard of it 14 because I left about that time. 15 Q. Would it seem interesting to 16 you, also, if what you had heard was totally 17 wrong? 18 A. I would like to see a report 19 of this study written by people competent in 20 writing and interpreting studies. 21 Q. Do you know what we'll do for 22 you, Doctor Wernicke, we'll get that for you and 23 have that for you tomorrow so you can be fully 24 informed concerning the results of that study. Page 82 1 We'll have it faxed up. 2 A. I appreciate that because I 3 always wanted to see that and I never had a 4 chance. 5 Q. All right. You will be 6 interested in seeing the results of that. In 7 fact, twice as many individuals taking Prozac 8 dropped out of that study than did individuals on 9 comparator or placebo drugs? 10 MR. LORE: Is that a question, Paul? 11 MR. SMITH: No. He said he was 12 interested in that, I'm just giving him 13 information I had off the top of my head. 14 MR. LORE: He'll be able to read it. 15 A. Dropped out of what? 16 MR. LORE: There's not a question 17 pending. 18 Q. Back to an in-depth discussion 19 concerning your meeting with Doctor Montgomery at 20 the Munich conference. Did you and Doctor 21 Montgomery discuss his proposal or his concept 22 that such a study as was done was being proposed? 23 A. I remember we talked about the 24 concept, not specifically about the study and how Page 83 1 it would be done, but just his concept of these 2 types of drugs versus tricyclics. 3 Q. Would you be comfortable in 4 referring to that study as a suicide prophylaxis 5 study? 6 A. Yes, I had heard it given that 7 term, yes. 8 Q. All right. Was Doctor 9 Montgomery discussing with you at that conference 10 the fact that he would like for Lilly to be 11 involved in that study? 12 A. I don't remember details of 13 that nature. I remember talking about the 14 general concept, but not the mechanism of who and 15 how and when. 16 Q. Was it Doctor Montgomery's 17 thought at that time that Prozac would reduce 18 suicidality? 19 A. His concept, as he explained 20 it to me, is that serotonin uptake inhibitors, 21 regardless of whether it was fluoxetine or 22 something else -- 23 Q. All right. 24 A. -- would do that. Page 84 1 Q. Okay. That was the premise -- 2 A. That was the premise. 3 Q. -- that he started off with. 4 He thought, based on his review of the 5 literature, that a serotonin specific reuptake 6 inhibitor would in fact reduce suicidality in 7 individuals who had that part of their presenting 8 problem, is that right? 9 A. Well, not necessarily 10 presenting problem. Overall, it is known that -- 11 it's been stated in the literature that about ten 12 percent of patients with major depressive 13 disorder commit suicide at some time, and his 14 premise was that that would be reduced if one 15 treated patients long-term with serotonin uptake 16 inhibitors. 17 Q. Was his proposal at that time 18 or what he was considering at that time to 19 administer these type of drugs to individuals 20 suffering from major depression? 21 A. Yes, as a prophylaxis after 22 their initial treatment phase. 23 Q. And did you do any further 24 work in connection with getting those studies Page 85 1 underway or overseeing those studies in any 2 manner? 3 A. Not of any real substance, 4 certainly not overseeing them. I might have had 5 some involvement in the concept, but not more 6 substantive than that. 7 Q. Was this a concept that you 8 thought would be worthy of Lilly's time and 9 expense? 10 A. I certainly thought that the 11 concept was worth investigating because of the 12 high mortality rate among depressed patients. 13 The fundamental question really related to what 14 do you do after the acute phase of treatment. 15 You can treat people and they can become 16 undepressed, but then what do you do, do you stop 17 treatment, do -- we know that this is a cyclic 18 disorder and that many patients may seem well and 19 then have a relapse and then go on to commit 20 suicide after having first gotten well. The 21 question is should you treat them, should you try 22 to prevent further episodes. And that was really -- 23 all of this was in the context of this larger 24 question. Page 86 1 Q. Of how far should you go -- 2 A. Correct. 3 Q. -- long-term in caring for 4 individuals suffering from depression? 5 A. Correct. Be it with 6 fluoxetine or some other medication. Because 7 it's a cyclic disorder, that was not -- there was 8 somewhat of a debate in the psychiatric 9 community, what's the right approach to long-term 10 therapy. 11 Q. Well, was it ever thought that 12 Prozac cured depression? 13 A. Not cured in the sense that if 14 you have an infection, you take an antibiotic, 15 it's gone, it will never come back. No, that was 16 never really considered because depression is 17 always thought to be sort of a life-long 18 condition, it's just a question of how many 19 relapses are there. 20 Q. All right. Are you of the 21 opinion that depressive disorders are related to 22 physiological conditions? 23 A. In many senses, yes, in that 24 there are abnormalities of neurotransmitter in Page 87 1 brain function, yes, I believe that, in many 2 cases. 3 Q. And based on your work at 4 Lilly and that time that you did follow the 5 psychiatric literature and observe the Lilly 6 clinical trials with respect to Prozac, did you 7 come to the conclusion that Prozac does indeed 8 have a physiological mode of action in human 9 beings? 10 A. I knew that fluoxetine has a 11 biochemical mechanism of action, I knew that we 12 had demonstrated efficacy in clinical trials. 13 The question is what is the exact relationship 14 between the two. So being a serotonin uptake 15 inhibitor, it can only be a presumptive causal 16 relationship to treatment of depression since 17 nobody really knows what is depression on a 18 molecular basis. 19 Q. But my question is that Prozac 20 does indeed inhibit uptake of serotonin? 21 A. Yes. 22 Q. And that is a physiological 23 response. 24 A. Yes. Page 88 1 Q. You're changing a 2 physiological condition in a human being when you 3 administer fluoxetine hydrochloride, Prozac. 4 A. Yes. 5 Q. Is that right? 6 A. That's correct. 7 Q. And it was demonstrated in 8 some individuals that that affected behavior in 9 the clinical trial. 10 A. It was demonstrated that this 11 compound alleviated the depression in many 12 patients. 13 Q. Okay. So that affected their 14 behavior? 15 A. Well, there are two issues 16 here, one is only presumed causal relationship 17 between serotonin and depression. What exactly -- 18 depression may be from something else that we 19 just don't know, serotonin may be the first in a 20 chain of events, we don't know exactly how that 21 impinges on depression. The other element that's 22 not quite correct about the proposition you posed 23 is that depression is not a behavior, depression 24 is a disease, not a behavior. One behaves in a Page 89 1 depressed manner, but behaviors are not diseases, 2 at least not in this sense. 3 Q. Well, can we say then that 4 Prozac affects certain of the symptoms of 5 individuals suffering from depression? 6 A. Yes. 7 Q. In other words, it may cause a 8 change in their mood so to speak. 9 A. Yes. 10 Q. We also know that -- or is it 11 true, sir, that based on your observations of the 12 clinical trials that Prozac has some 13 physiological effects? 14 A. Yes. 15 Q. Some people may become 16 nauseated when they take Prozac. 17 A. Yes, that was observed. 18 Q. That is a physiological 19 response as a result of the ingestion of Prozac. 20 A. Yes. 21 Q. In some individuals. 22 A. Yes. 23 Q. And I'm not saying all 24 individuals. Page 90 1 A. Correct, I would say that 2 that's true. 3 Q. Some people had trouble with 4 sleep following ingestion of Prozac. 5 A. Yes. 6 Q. Some people had increases or 7 had anxious anxiety symptoms following taking 8 Prozac. 9 A. Yes, just as in the placebo 10 group and in other groups. 11 Q. But at greater instances than 12 placebo. 13 A. Somewhat greater. 14 Q. All right. So there was a 15 conclusion that Prozac can cause agitation in 16 some individuals. 17 A. Certainly anxiety. 18 Q. All right, anxiety. 19 A. There's somewhat of a 20 difference between agitation and anxiety. 21 Q. Now are you speaking with 22 psychiatric expertise when you say that, Doctor 23 Wernicke? 24 A. I'm speaking from what I Page 91 1 observed in doing the clinical trials and what 2 the investigators told me, so I'm not -- it's not 3 my personal expertise. We talked to a lot of 4 investigators who are psychiatrists and they've 5 made that distinction. 6 Q. And your opinion may be 7 somewhat expert in these matters of psychiatry, 8 but certainly -- and the Prozac clinical trials, 9 but certainly you would defer to the expertise of 10 the Lilly psychiatrists in these matters. 11 A. Yes. 12 Q. And to the expertise of the 13 Lilly clinical investigators who were 14 psychiatrists in these matters, would you not? 15 A. Yes. 16 Q. Because you're trained as a 17 pediatric neurologist. 18 A. Correct. 19 Q. Which is not a psychiatrist. 20 A. That's right. 21 Q. Different examination of the 22 brain, correct? 23 A. Yes. 24 Q. But it became clear during the Page 92 1 clinical trials that individuals were manifesting 2 different physiological responses to Prozac, did 3 it not? 4 A. I'm sorry, different than 5 what? 6 Q. Different than if they hadn't 7 taken it. People -- some people would become 8 nauseated after they took Prozac. 9 A. Yes, that's correct, some 10 would. 11 Q. Some people would have anxiety 12 after taking Prozac. 13 A. Yes. 14 Q. Some people would have 15 nervousness. 16 A. Yes. 17 Q. Some people would complain of 18 headaches. 19 A. Yes. 20 Q. These are physical side 21 effects of taking the medication. 22 A. See, that's where their causal 23 relationship is placed down, because you said 24 people reported these, and they did, but all of Page 93 1 those things were reported with placebo. So -- 2 Q. But they were reported in 3 greater instances -- 4 A. I understand that, but that's 5 exactly the point. For an individual patient, 6 one cannot say this was because they took this 7 drug and -- 8 Q. Okay. 9 A. Let me finish the thought, 10 because I think it's very important that all who 11 read or see this understand that. When you look 12 at a clinical trial, results of a trial, one can 13 only compare groups, one can compare the numbers 14 in one versus the other. Like you said, there 15 was a greater rate of reports. But for any 16 individual patient, unless one withdraws them and 17 rechallenges them in a controlled manner, one 18 cannot conclude what, for that patient, the 19 causal relationship was. And that's a very 20 important distinction because one cannot 21 extrapolate from the group to the individual. 22 Q. Then why give the medication 23 to the group in a clinical trial, Doctor 24 Wernicke, if you're not trying to get some type Page 94 1 of scientific insight concerning the propensities 2 of the drug? 3 A. You are trying to gain insight 4 into the propensities of the drug but only in a 5 group sense, and that's the only way you can do 6 it because for an individual it's very hard to 7 determine what is the cause and effect 8 relationship. 9 Q. And you're saying that -- 10 well, could we say this, based on your 11 experiences as a scientist, a physician, and as 12 medical monitor or clinical research physician on 13 the Prozac clinical trials, that the clinical 14 trial data is valuable to a great extent? 15 A. Absolutely. 16 Q. And you're saying one of the 17 reasons for that is because it compares groups. 18 A. Yes. 19 Q. And you can draw some 20 scientific judgments based on comparing these 21 groups in the clinical trials. 22 A. On a group level. 23 Q. On a group level, yes. 24 A. Yes. Page 95 1 Q. And you are drawing those 2 judgments not only with respect to the efficacy 3 of Prozac, but with respect to the safety of the 4 drug. 5 A. Yes. 6 Q. That's one of the purposes of 7 the clinical trials. 8 A. Yes. 9 Q. But what you're saying is that 10 doesn't mean that you can take the clinical trial 11 data and say that's conclusive concerning whether 12 or not Prozac caused a particular behavior in a 13 particular individual. 14 A. That's true, and that's true 15 for efficacy, too. 16 Q. All right. So that's what you 17 consider an important distinction to be made, is 18 that right? 19 A. I would say that, yes. 20 Q. There are other things that 21 need to be taken into consideration in making a 22 determination with respect to whether or not a 23 particular individual is experiencing a 24 particular reaction to Prozac, is that right? Page 96 1 A. Yes, as far as can be off and 2 it's unknown, and you can't define everything. 3 Q. But to get a better scientific 4 insight with respect to a particular individual, 5 there's other data that would be helpful, 6 correct? 7 A. Yes. 8 Q. For instance, the 9 post-marketing data on a drug is also helpful in 10 examining the issue with respect to whether or 11 not the product is causally related to the 12 particular behavior or response of an individual, 13 is it not? 14 A. I see the post-marketing data 15 just as an extension. The same qualifiers that 16 hold true for the control studies hold true for 17 post-marketing. 18 Q. But even though the 19 post-marketing data has limitations, it is 20 scientifically valid to look at that data in 21 making the particular determination or 22 investigation. 23 A. Not on a comparator basis, no, 24 I would not say it's scientifically valid. It's Page 97 1 much less valid because you don't have a 2 comparator. 3 Q. Well, whether it's better or 4 worse, it's also something that is scientifically 5 useful in looking at the question. 6 A. It is in the context of what 7 it is. 8 Q. Okay. 9 A. But no more. You can't make 10 more than there is out of it because it's totally 11 uncontrolled. 12 Q. I understand that, but in fact 13 the FDA requires -- 14 A. Yes. 15 Q. -- manufacturers of drugs to 16 advise them of adverse reactions with the drug, 17 don't they? 18 A. Yes. 19 Q. And the FDA is interested in 20 that information, aren't they? 21 A. Yes, as are companies. 22 Q. And the reason for that is 23 that that may bear on the safety of the drug, 24 correct? Page 98 1 A. Yes, that is the main purpose. 2 Q. In fact, Eli Lilly and Company 3 maintains sophisticated computer hardware to 4 record adverse experiences in connection with 5 Prozac in all of the drugs it manufactures, don't 6 they? 7 A. Yes. 8 Q. That's called the DEN system, 9 isn't it? 10 A. Yes. 11 Q. That's the drug experience 12 network -- 13 A. Yes. 14 Q. -- correct? So that's all, or 15 ninety-nine percent, post-marketing data that's 16 in the Lilly DEN system, isn't it? 17 A. By this time, I presume that 18 would be true. That, of course -- that 19 percentage gets larger and larger the longer 20 after marketing. 21 Q. Certainly. The DEN data may 22 have some clinical trial data in it, but by now, 23 1994, the majority of the data in the DEN system 24 at Eli Lilly in connection with Prozac would be Page 99 1 post-marketing data. 2 A. I would believe so, yes. 3 Q. That data, Lilly considers it 4 of some scientific interest and value. 5 A. Yes. 6 Q. Is that correct? 7 A. I would think so, we certainly 8 did. 9 Q. And the Food and Drug 10 Administration obviously requires that of some 11 scientific interest and value, don't they? 12 A. Yes. 13 Q. Because they require it. 14 A. I would believe so. 15 Q. And there is a percentage of 16 our tax dollar that goes to the Food and Drug 17 Administration that's devoted to examining 18 post-marketing adverse events of products, 19 correct? 20 A. I presume so. I don't know 21 about the money flow of the government, that's a 22 mystery to me. 23 Q. Well, you don't know how much 24 it is, but you know that the FDA -- Page 100 1 A. I know they do it, and I know 2 we pay for it, but that's -- 3 Q. When you say we, you're 4 talking about you and I as taxpayers? 5 A. Taxpayers, of course. 6 Q. And that's not necessarily a 7 bad governmental function that our tax dollars go 8 to support, is it, Doctor Wernicke? 9 A. I certainly think it's not a 10 bad function, I never suggested it was. What I 11 suggested is it has limitations on it. 12 Q. As does the clinical trial 13 data has limitations, doesn't it? 14 A. They're somewhat different, 15 yes. 16 Q. All right. My only point is, 17 clinical trial data has advantages and 18 disadvantages, doesn't it? 19 A. Yes. 20 Q. Th spontaneous reporting 21 system of post-marketing events has advantages 22 and disadvantages also, doesn't it? 23 A. I would agree with that. 24 Q. One of the advantages of the Page 101 1 post-marketing data is that there is a broader 2 group of individuals to whom the drug is exposed. 3 A. Certainly larger numbers. 4 Q. Larger numbers? 5 A. Yes. 6 Q. And those individuals who get 7 Prozac in the post-marketing regime who are 8 reporting adverse events through the spontaneous 9 reporting system are individuals different from 10 individuals in the clinical trials because 11 they've not been subject to any inclusion or 12 exclusion criteria, have they? 13 A. Only in the sense of whether 14 their physician decides to prescribe the drug, 15 certainly not of a study. 16 Q. Right. And the study was 17 carefully controlled, who would be administered 18 Prozac, right? 19 A. Yes. 20 Q. By Lilly and their 21 investigators. 22 A. Yes. 23 Q. And the protocols for those 24 clinical trials had specific inclusion and Page 102 1 exclusion criteria that the investigator must 2 follow in determining whether or not a patient 3 should be in the clinical trials, correct? 4 A. Correct. 5 Q. But the prescription on the 6 street, the private doctor trying to help 7 patients who prescribes Prozac, doesn't have such 8 a regimented inclusion and exclusion criteria, 9 does he? 10 A. That's correct. 11 Q. So that's a difference in the 12 number and type of individuals who will 13 experience adverse reactions that will be 14 reported to the spontaneous reporting system? 15 A. The type, you have to presume, 16 because you don't in fact know what type. It 17 could be that they are virtually the same type, 18 but you just don't know that, you can't document 19 that. So I can't speak to the type of individual 20 that would be in that data base. 21 Q. But they certainly wouldn't 22 have to meet any exclusion or inclusion criteria 23 with clinical trial, would they? 24 A. That's correct, they wouldn't Page 103 1 have to. 2 Q. Then you mentioned another 3 thing that would be scientifically valuable in 4 examining the issue of the effect of the drug 5 would bu, did you say, a rechallenge? 6 A. Well, if you have a presumed 7 cause, for instance if a patient takes a drug and 8 they get a rash, you say well, a lot of things 9 cause rash, so you withdraw the drug and the rash 10 goes away, but that doesn't prove the drug did it 11 because a lot of rashes go away. If the patient 12 was really dependent on that drug, if that was 13 the only option and it was decided well, let's 14 try that patient again to see if that happens 15 again, that would be a rechallenge. 16 Q. All right. 17 A. That's the only real way to 18 show a good cause and effect relationship. And 19 even that really needs to be done in a number of 20 patients to be really valid. 21 Q. So you said that the best way 22 is this rechallenge way, where if a patient 23 experiences a particular reaction, they're taken 24 off the medication and it goes away, then you Page 104 1 readminister the medication and if it reappears, 2 you have better evidence that there may be a 3 causal relationship -- 4 A. Yes. 5 Q. -- between the drug and the 6 reaction? 7 A. Yes, that is correct. And as 8 you said, may be. It still is not absolutely 9 definitive proof, but within the context of what 10 you have. 11 Q. And I'm talking about within 12 reasonable medical determination. 13 A. Yes, I would agree with that. 14 Q. Do you know of any rechallenge 15 study that was done on Prozac for any particular 16 reaction? 17 A. As I remember, there was in 18 one case of rash there may have been a 19 rechallenge. It was never a study with a number 20 of patients, this was done on a case-by-case 21 basis. 22 Q. Okay. How was that 23 accomplished? 24 A. Pardon me? Page 105 1 Q. How was that accomplished? 2 A. The investigator very 3 carefully followed the patient to see if that 4 event reoccurred, waited for the event to 5 disappear, and in this case it would have been 6 the rash, and then very carefully reintroduced 7 the medication. 8 Q. And it was done on a 9 case-by-case basis during the clinical trial? 10 A. Yes. Well, it could be 11 afterwards, too, but -- 12 Q. That was going to be my next 13 question. Do you know whether or not it was done 14 in any post-marketing situation? 15 A. I'm not aware of any. 16 Q. Do you know of any other 17 instance in which rechallenge was used to 18 determine whether or not a particular reaction 19 was being caused by Prozac? 20 A. I vaguely remember there were 21 some instances of elevated liver function 22 enzymes, which again has many different causes, 23 where patients were withdrawn and everything was 24 back in the normal range. One or two patients Page 106 1 had the drug introduced, I don't remember very 2 specifically. 3 Q. In the other instances where 4 Lilly did a rechallenge analysis of a particular 5 medical situation or psychiatric situation, it 6 came up in the use of Prozac? 7 A. I'm not aware of any. 8 Q. Let's go back to our 9 discussions with Doctor Montgomery. You talked 10 about a suicide prophylaxis study, correct? 11 A. Yes. 12 Q. And what else was discussed in 13 connection with the prophylaxis, suicide 14 prophylaxis study? 15 A. I don't remember anything 16 else. 17 Q. At the time you had this 18 discussion with Doctor Montgomery concerning 19 suicide prophylaxis, had the BGA raised the issue 20 that they were concerned that there might be a 21 relationship between Prozac and suicidality and 22 violent aggressive behavior? 23 A. I don't remember the BGA ever 24 saying anything about violent aggressive behavior Page 107 1 when I was there, and -- 2 Q. Okay. 3 A. Wait a minute, let me finish. 4 Q. No, I just said okay. 5 A. And the way that -- it was in 6 the context of here are these numbers, you have 7 reported these numbers of deaths and suicide, 8 explain them; there is a relationship here, prove 9 it one way or the other. There's a difference to 10 that. We had a lot of questions because they 11 just didn't quite see how we interpreted that, 12 how we got there, why we said what we did. They 13 wanted further explanation, and that does not 14 mean that they proposed that there was a causal 15 relationship, which is always inherent in your 16 question, that's why I feel that I have to 17 qualify that. When I was there, we were given a 18 list of questions and they made these 19 observations and explained these things and that 20 was that. Now what went on in their minds, I 21 can't say. 22 Q. I'm going to give you an 23 opportunity -- we're going to discuss that in 24 some real specific detail with some documents, Page 108 1 all right -- 2 A. Uh-huh. 3 Q. -- in English and in German, 4 for your benefit. But my question to you, Doctor 5 Wernicke, simply was had the BGA expressed these 6 questions at the time you had your discussion 7 with Doctor Montgomery concerning the suicide 8 prophylaxis study? That's all I was asking. 9 A. Yes, they expressed the 10 questions about suicide. I don't remember 11 anything about aggressive behavior from the BGA, 12 certainly at that point, that I was aware of. 13 Q. Okay. So you knew that the 14 BGA had asked those questions -- 15 A. Yes, about suicide. 16 Q. -- when you talked with Doctor 17 Montgomery? 18 A. Yes. 19 Q. Did you discuss that fact, 20 that the BGA had asked some questions, with 21 Doctor Montgomery? That's all I want to know 22 now. I want to know other things, but that's all 23 I want to know now. 24 A. I don't remember discussing Page 109 1 that because this was sometime later, this was 2 several years after the BGA round of questions, 3 so I don't remember if we discussed that. 4 Q. All right. Do you recall any 5 other discussions with Doctor Montgomery at that 6 time, at the occasion of this Munich psychiatric 7 conference? 8 A. No, I don't. 9 Q. Can you pin down that date 10 when this conference was any more? You came in 11 June of '84. 12 A. The closest I can say would be 13 about '88, somewhere around there. It was 14 shortly after or shortly before we got approval 15 in the U.S., but I don't really remember. 16 Q. The approval in the U.S. was 17 December of '87. 18 A. Right. 19 Q. So '88 -- 20 A. It could have been '88, it 21 could have been '86, I just honestly don't 22 remember. 23 Q. Do you remember whether it was 24 cold or -- Page 110 1 A. No, it wasn't cold, it was in 2 the summer. I remember we walked down the 3 street. I remember walking down the street with 4 Doctor Montgomery and his wife was there and we 5 talked about a lot of things and we talked about 6 this concept. 7 Q. Did Doctor Montgomery speak 8 German? 9 A. No -- well, if he did, not to 10 me. He spoke English. 11 Q. Was your wife with you? 12 A. No. 13 Q. And you don't recall anybody 14 else with Lilly in the United States there at 15 that meeting? 16 A. I remember Ray Fuller being -- 17 not at this meeting with Doctor Montgomery, at 18 the scientific meeting I believe Doctor Fuller 19 was there. 20 Q. What was he doing there? 21 A. Well, he was one of the 22 founders of the whole serotonin concept, and 23 these meetings have a great deal of basic 24 scientific content, it was not just a clinical Page 111 1 psychiatric meeting. So there was a lot about 2 other drugs, mechanism of action, very 3 fundamental basic science concepts. 4 Q. Okay. Who was there from 5 Germany that was employed by Lilly? 6 A. I don't remember. 7 Q. Was Doctor Hans Weber there? 8 A. I'm trying to remember the 9 people that I remember seeing, and I just don't 10 remember him being there. 11 Q. Was Doctor Schulze-Solce 12 there? 13 A. I don't believe so, I don't 14 remember him. 15 Q. Was Doctor Von Keitz there? 16 A. I don't believe she's a 17 doctor. 18 Q. Was Doctor -- was he there? 19 A. She, it's a woman, Barbara Von 20 Keitz. I don't remember her being there. 21 Q. How about Doctor Schenk? 22 A. I don't believe Doctor Schenk 23 was with Lilly anymore at that time. The reason 24 I remember that is because I know she went with Page 112 1 another company and I went to their exhibit to 2 see if I could see her. So she would not have 3 been there for Lilly, and in fact, I did not see 4 her. 5 Q. All these people I mentioned, 6 you know? 7 A. Yes. 8 Q. My question is, were they 9 there at this -- 10 A. I understand the question. I 11 don't -- when I say were they there, I want to 12 have a specific memory in my mind, having seen 13 them, talked to them. Now if you ask me could 14 they have been there, they probably could have 15 been, but I don't remember specifically seeing 16 them. 17 Q. How about Claude Bouchy, was 18 he there? 19 A. I don't remember him being 20 there. 21 Q. How about S. Heymanns? 22 A. Actually, I don't know who 23 that is. The name I've seen on some documents, 24 but I don't remember meeting that person. Page 113 1 Q. When did you see Heymanns' 2 name on any documents? 3 A. Some in my tenure at Lilly on 4 a list of people, things that were distributed. 5 I remember that name, but I don't remember 6 specific instances. 7 Q. Okay. You mentioned Doctor 8 Laakman and Doctor Montgomery as individuals that 9 you met with at that meeting. Anybody else? 10 A. Those are the only individuals 11 that I can remember. 12 Q. I assume that you're 13 proficient in the use of the German language? 14 A. I was nine years old when I 15 left there, so I would say my medical vocabulary 16 is rather limited, so I would not say I'm 17 proficient in that. Certainly if I go over 18 there, I can easily get around, but my vocabulary 19 is somewhat limited and I wouldn't feel 20 comfortable in writing a scientific article in 21 German. 22 Q. Well, you certainly speak and 23 read German. 24 A. Yes. Page 114 1 Q. And there may be some 2 technical or scientific terms that you might have 3 some difficulty with, correct? 4 A. Yes. 5 Q. But you're proficient in the 6 German language, are you not? 7 A. To the extent that I 8 explained, yes. Remembering that I was nine 9 years old when I left, and I've picked up 10 something since then, but it's not like I've 11 lived and worked there all the time. 12 Q. But until you left home, your 13 parents spoke German in the home on occasion, did 14 they not? 15 A. Yes. 16 Q. And your parents had moved 17 back to Germany. 18 A. Yes. 19 Q. Are they still alive? 20 A. Yes. 21 Q. You still speak with them? 22 A. Yes. 23 Q. And most of your 24 communications with them are in German, are they Page 115 1 not? 2 A. Yes. 3 Q. And you still have a brother 4 that lives in Germany. 5 A. Yes. 6 Q. And you speak with him 7 regularly? 8 A. Yes. 9 Q. And you speak with him in 10 German regularly? 11 A. Sometimes English, sometimes 12 German. He's totally bilingual because he was 13 born in the United States and went to school 14 here, so he can go back and forth. 15 Q. You're totally bilingual, too, 16 aren't you, Doctor Wernicke? 17 A. Not to the extent that he is, 18 not in a technical arena, certainly. 19 Q. Is your brother a medical 20 doctor or scientist? 21 A. No. 22 Q. Does your wife speak German? 23 A. No. 24 Q. Do your children speak German? Page 116 1 A. No, just a few words that I've 2 taught them. 3 (A SHORT RECESS WAS TAKEN.) 4 (PLAINTIFFS' EXHIBIT NO. 1 WAS 5 MARKED FOR IDENTIFICATION AND 6 RECEIVED IN EVIDENCE.) 7 Q. Doctor, we've handed you an 8 exhibit which has been marked as Exhibit 1, and 9 we'll ask you to review that a minute, please. 10 A. Okay. 11 Q. Exhibit 1 apparently is a 12 telex from Bad Homburg dated June 8, 1984 13 authored by J. Schenk and H.J. Weber, is it not? 14 A. Yes. 15 Q. And it's directed to Doctor 16 Robert Zerbe in Indianapolis, correct? 17 A. Yes. 18 Q. You are not included on that 19 list of individuals to receive copies of this 20 document, are you? 21 A. That's correct. 22 Q. That's probably because you 23 had been on the job for maybe one week at the 24 time this document was authored, correct? Page 117 1 A. I wasn't even there then at 2 all, I didn't come until the end of June, 1984. 3 Q. All right. This is something 4 that preceded you at Lilly then? 5 A. Right. 6 Q. After you got to Lilly, did 7 you ever see this document? 8 A. I don't remember seeing this 9 document. 10 Q. To this date, have you seen 11 this document? 12 A. No. 13 Q. Item -- well, the document, by 14 reading it, apparently is a request from Germany 15 to Indianapolis to supply information to your 16 German affiliate so that they might use this 17 information in answering questions with 18 regulatory authorities in Germany, is it not? 19 A. Yes, it appears to be. 20 Q. And item three on page two 21 requests, quote, in-depth analysis of suicides 22 and suicide attempts, paren, patient by patient, 23 timing, symptomatology at entry into the trial, 24 comma, phase of trial, and any other clinically Page 118 1 relevant comments, close paren, period, close 2 quote, right? 3 A. Yes. 4 Q. Do you know why the German 5 regulatory authorities were requesting this 6 information concerning suicides and suicide 7 attempts? 8 A. Yes. 9 MR. SMITH: Let's take a break and 10 change the tape. 11 (A SHORT RECESS WAS TAKEN.) 12 Q. Why was it then, Doctor 13 Wernicke, that the German regulatory authorities 14 were wanting this analysis of suicide and suicide 15 attempts? 16 A. From what I understand, the 17 information they had was taken directly from our 18 NDA submission. The way the process worked is 19 that we, Lilly in Indianapolis corporate 20 headquarters, would send copies of our submission 21 to their foreign affiliates and they would then 22 subset those for -- extract whatever they needed, 23 or it might have been the whole body of data, and 24 submit it to their local government. In that Page 119 1 report to the NDA were a listing of all the 2 deaths and suicides, and the numbers were just 3 given, and I don't remember them exactly, but I 4 know there were quite a few more on fluoxetine 5 than there were on comparitors. If I remember, 6 it was like twelve fluoxetine, and two 7 comparator, something in that range. And that 8 was apparently just stated that way, there was no 9 consideration of how many patients were in the 10 denominator, how many patients had been exposed 11 to both of these groups and what the duration of 12 treatment was. So the numbers, at least the way 13 the questions were expressed, is why are there so 14 many more deaths and suicides on fluoxetine than 15 on comparator, be it twelve or two or eight or 16 two, I don't remember exactly. 17 Part of our explanation was to 18 explain what the denominator was, which for one 19 thing there were many more on fluoxetine although 20 I don't know exactly the same numbers, but more 21 importantly, the duration of therapy was much 22 longer. And that also included what we called 23 compassionate-use studies for patients that 24 basically had a severe illness that for some Page 120 1 reason could not get in a study or there wasn't 2 one available. So there were seriously ill 3 patients that were only treated with fluoxetine, 4 which presumably would be at a much higher risk. 5 Q. We'll get to that. But my 6 question, Doctor Wernicke, was who told you this 7 or how did you know that in early June, 1984 that 8 these were the reasons that the BGA was 9 requesting this in-depth analysis of suicides and 10 suicide attempts? 11 A. I don't remember whether any 12 particular person told me that. What we did -- 13 what I did is went back and tried to sort out or 14 figure out exactly what they had seen, why -- I 15 was at the same point, why are they asking this 16 question. So I backtracked, and the only source 17 of information, since I didn't have their 18 submission, was our NDA. 19 Q. Well, but my point is or my 20 question is, did somebody talk with the BGA in 21 early June and ask them why they wanted the 22 suicide data or is this just your assumption 23 based on -- and we have this correspondence over 24 a course of time that indicates some of your Page 121 1 thoughts, that this is why the BGA was asking 2 this. My question is, what was it that somebody 3 at the BGA said to you that makes you think this 4 is the reason they were wanting this in-depth 5 analysis of suicide? 6 A. Nobody from the BGA said 7 anything to me personally. 8 Q. All right. So when you see, 9 as stated here in Exhibit 1, point three, that 10 the BGA was requesting this in-depth analysis, 11 the reasons are not apparent. 12 A. Not from this document in and 13 of itself. That's why I explained the process 14 and how I backtracked and came to that 15 conclusion. 16 Q. All right. Now let me ask you 17 now, at this point, what is your understanding of 18 what the BGA had in front of them in connection 19 with the application of fluoxetine to be approved 20 in Germany? 21 A. It was all or part of the NDA 22 we submitted to the FDA. 23 Q. When you say all or part of 24 the NDA, that doesn't give us any information at Page 122 1 all. Was it all or was it part? 2 A. I'm sorry, I just don't know. 3 Q. Then say I don't know. Don't 4 say all -- don't leave the implication that all 5 of the information that was submitted to the NDA 6 was submitted to the BGA, and then say part if 7 you don't know. 8 A. I didn't imply that. I said -- 9 I told you before the process that was used, and 10 which was that the NDA was sent to the affiliates 11 and they would then extract what information they 12 thought appropriate for their local submission. 13 But I didn't see that submission, so I can't be 14 certain what part or perhaps whether they 15 submitted all of it. That's why I say it's some 16 subset, but I don't know the extent of that 17 subset. 18 Q. Well, was there an in-depth 19 analysis of suicide and suicide attempts, as is 20 requested in Exhibit 1, contained within the NDA 21 that was submitted -- 22 A. No. 23 Q. -- to the United States Food 24 and Drug Administration? Page 123 1 A. No, because this was 2 afterwards. This -- the material was submitted, 3 and these questions followed that. 4 Q. So there were just raw data 5 that had been submitted to the Food and Drug 6 Administration? 7 A. Perhaps a little more than 8 that, but essentially I would say that is, as I 9 remember, the table, it's pretty much like that. 10 Q. Okay. So I can understand 11 this, as far as you know, on June 8, 1994, the 12 United States Food and Drug Administration did 13 not have a, quote, in-depth analysis of suicides 14 and suicide attempts, patient by patient, timing, 15 symptomatology at entry into the trial, phase of 16 trial, and any other relevant -- clinically 17 relevant comments, is that correct? 18 A. I presume that's correct 19 because I know of no subsequent submissions that 20 dealt with that, as far as I know it was only 21 what was contained in the NDA. 22 Q. All right. The authors, 23 Doctors Schenk and Weber, of this document, on 24 the first page of this document characterized Page 124 1 this as very urgent, correct? 2 A. Yes, I see that. 3 Q. And in fact they say very 4 urgent, very urgent, very urgent, very urgent, 5 very, don't they? 6 A. Yes. 7 Q. They use very, one, two, 8 three, four, five times, right? 9 A. Yes. 10 Q. And urgent, four times, right? 11 A. Yes. 12 Q. Would you agree that a reading 13 of this would indicate that Schenk and Weber felt 14 that this was an important matter? 15 A. In either substance or timing 16 or both, perhaps, I can't conclude that, which 17 was which. 18 Q. When you started with Lilly, 19 did you know that there was a situation existing 20 in Germany, that there was a need for information 21 by your German affiliate in connection with 22 analysis of suicides and suicide attempts? 23 A. No. 24 Q. When did you first learn of Page 125 1 that? 2 A. Within several weeks or a 3 month of my being there. 4 Q. All right. And how did you 5 first learn this? 6 A. I took over the fluoxetine 7 project and became involved, and in the course of 8 that became aware of it, I can't exactly say 9 when. 10 Q. Who brought you up-to-date on 11 the fluoxetine project? Here you are right out 12 of your training, you've been hired by Lilly, all 13 of a sudden you're taking over all of the United 14 States clinical trials on an important 15 antidepressant for a major pharmaceutical firm, 16 correct? 17 A. Correct. 18 Q. Who brought you up to speed on 19 these issues? 20 A. A number of people. Bob Zerbe 21 was my division director, I spent time with him 22 going over where we were. Paul Stark, who I took 23 over from. I talked to a number of other people 24 in the company that were involved with this, and Page 126 1 other projects I was involved in. So I talked -- 2 there was no one particular person that did 3 everything, I just absorbed from a lot of people. 4 Q. All right. 5 (PLAINTIFFS' EXHIBIT NO. 2 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Can you identify Exhibit 2? 9 A. Well, I signed it. It's a 10 memo written by me, and I don't remember who it's 11 addressed to, basically introducing myself as 12 taking over from Paul Stark. 13 Q. And this is dated August 23, 14 1984, is it not? 15 A. Yes. 16 Q. And would it be reasonable to 17 assume that this was probably an investigator in 18 the Prozac clinical trials? 19 A. That would probably be a 20 pretty good assumption. When I read it, I was 21 thinking of somebody internal, but that makes 22 sense. I suspect now that yes, that probably is 23 correct. 24 Q. By virtue of the copies, the Page 127 1 individuals who received copies, these are 2 clinical research assistants, are they not? 3 A. Yes, except Doctor Dolman. I 4 can't remember exactly how he was involved. 5 Q. Who is Doctor Dolman? 6 A. That's a good question, I 7 don't remember Doctor Dolman. 8 Q. Who is Melissa Au? 9 A. She was a clinical research 10 associate, and now is Melissa Humbert. She 11 managed and handled the data on some of these 12 studies. 13 Q. Have you been able to identify 14 Exhibit 3? 15 A. It's identical to Exhibit 1, a 16 copy of the same memo. 17 Q. Oh, I'm sorry, you know I told 18 you I wanted to trick you, and then again, I did. 19 A. I guess you just can't help 20 it. 21 MR. SMITH: Can we take that Exhibit 3 22 off there so we won't have two Exhibit 3s, and 23 put it on the right exhibit? 24 MR. LORE: That will be fine. Page 128 1 (PLAINTIFFS' EXHIBIT NO. 3 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. All right. Doctor Wernicke, 5 Exhibit 3 is a telex dated June 29, 1984. 6 A. 26th, sent on the 26th. The 7 date on the top is the 29th. Look at the Bad 8 Homburg, June 26 there. Are we looking at the 9 same thing? 10 Q. All right. 11 A. I know it's stamped June 29th 12 on the top, but -- 13 Q. That document has to do with 14 registrations of Prozac in Germany, does it not? 15 A. Yes. 16 Q. It's authored by Doctors 17 Schenk and Weber, correct? 18 A. Yes. 19 Q. And it has to do with their 20 efforts to get Prozac registered in Germany, 21 correct? 22 A. Yes. 23 Q. And it appears to be also a 24 follow-up with various discussions with marketing Page 129 1 at the fluoxetine symposium at the 14th CINP 2 Congress. 3 A. Medical and marketing. 4 Q. All right. 5 A. Yes. 6 Q. And what is the 14th CINP 7 Congress? 8 A. CINP is an international 9 neuropharmacology meeting, similar to the 10 clinical scientific psychiatry meetings that I 11 testified earlier. This is more science related. 12 Q. Heavy stuff? 13 A. Fairly heavy for the 14 nonconsumer of that, yes. 15 Q. All right. If you will turn 16 to point three on Exhibit 1, and point fourteen 17 on Exhibit 3, we'll come back to my question 18 concerning why did the BGA request this in-depth 19 analysis of suicides. Point three on Exhibit 1, 20 the June 8 telex, requests an in-depth analysis 21 of suicide and suicide attempts, does it not? 22 A. Yes. 23 Q. And then if you look at 24 Exhibit 3, on point fourteen, it says as we've Page 130 1 already explained by our telex to Doctor Zerbe of 2 June 8, 1984, which is Exhibit 1, is it not? 3 A. Yes. 4 Q. We need a careful analysis of 5 suicide and suicide attempts, correct? 6 A. Yes. 7 Q. They also talk about side 8 effects, don't they, in that paragraph, paragraph 9 fourteen? 10 A. I don't see anything about 11 side effects in paragraph fourteen. 12 Q. Doesn't it say side effects, 13 et cetera, at the end of the first paragraph? 14 A. Yes, it does, severity on 15 entry. 16 Q. It also talks about doses -- 17 A. Uh-huh. 18 Q. -- doesn't it? 19 A. Yes. 20 Q. They want to know, in this 21 in-depth analysis, data concerning the doses that 22 these individuals were on when they committed 23 suicide or attempted suicide, right? 24 A. Yes, they wanted a profile. Page 131 1 Q. Now, point fourteen on Exhibit 2 3 goes on to explain a little further point three 3 of Exhibit 1, doesn't it? 4 A. It appears to. 5 Q. By saying this is a very 6 serious issue in the opinion of the BGA. It 7 might well be that we will have to recommend 8 concomitant tranquilizer intake for the first two 9 or three weeks in the package literature, end 10 quote, doesn't it? 11 A. Yes. 12 Q. All right. Did you speak with 13 anybody in June or July, either in Germany or in 14 the United States, as to why the BGA would 15 consider this a serious issue? 16 A. I don't remember specific 17 discussions about why the BGA -- what they might 18 have thought or why they stated that. 19 Q. This does -- this is a memo 20 from Lilly employees in Germany, is it not? 21 A. Yes. 22 Q. And they are characterizing 23 the suicide analysis and suicides as a serious 24 issue in the opinion of the BGA, are they not? Page 132 1 A. That's what they say. 2 Q. And they go on to say that it 3 might well be that we will have to recommend 4 concomitant tranquilizer intake for the first two 5 or three weeks in the package literature, doesn't 6 it? 7 A. It says that, yes. 8 Q. Did you have any idea at the 9 time, in June or July, 1988 -- '84, as to why the 10 German government would request in the package 11 literature concomitant tranquilizer use? 12 A. I have an idea, I can't say 13 with certainty that that came to my mind in 1984, 14 but I do believe I understand the basis for that. 15 Q. All right. What is the basis 16 for that, based on your present understanding? 17 A. In Europe, and I think 18 particularly in Germany, it appears depression is 19 thought of somewhat differently than in the 20 United States, and I believe this is just sort of 21 a cultural difference in the psychiatric 22 community. They make a much sharper distinction 23 between agitated and sedated depression or 24 retarded depression, as it's often called. They Page 133 1 look at it more as different types, and one sees 2 that concept coming through a lot of the 3 questions. Whereas in the United States, my 4 understanding is it's thought of more as a 5 continuum. There are certainly patients that 6 have more retarded features, there are some that 7 have more agitated features, some have both, and 8 in fact there's a subcategory agitated and 9 retarded, which seems to be a contradiction in 10 terms but it isn't really. So the backdrop of 11 the German psychiatric community is much more in 12 focus with that concept. 13 Q. Is that right or wrong? 14 A. I don't know. I don't think I 15 know -- well, I know I don't know, I don't 16 believe anybody knows, and I suspect what I have 17 seen is that some people seem to fit into these 18 categories, others don't. I can't give a 19 judgment as to what they're on. 20 Q. Is there a scientific basis 21 for this German philosophy or practice of tending 22 more to characterize patients in the agitated 23 versus retarded depression categories? 24 A. My opinion is that there Page 134 1 really is very little or there's more scientific 2 basis for the opposite, that in fact it's a 3 continuum, and that patients, individual patients 4 can express different manifestations at different 5 times. From what I've seen, and again I'm not a 6 psychiatrist, there's no distinct neurological 7 disease entity of retarded depression versus 8 agitated depression, and in fact we've seen this 9 in patients, and you can see this, that patients 10 may go from one extreme to the other or be 11 somewhere in between. Now to say that there's 12 scientific evidence for the German concept would 13 be to say these people are losing one disease and 14 developing another. What makes more sense to me, 15 looking at it from a physiological standpoint, is 16 at different times they have different 17 manifestations of the same disease. 18 Q. That could also be what the 19 Germans are saying, too, isn't it? 20 A. Perhaps, but they make the 21 distinction much more sharply, and traditionally 22 they have. 23 Q. Well, my point simply is, that 24 doesn't mean that the Germans are wrong or that Page 135 1 it's inaccurate scientifically to make that 2 distinction, if they are indeed making that 3 distinction? 4 A. Right. I'm not saying that 5 they're wrong. 6 Q. Go ahead. 7 A. Let me explain a little bit of 8 where -- 9 Q. Again, we're in the context of 10 why the BGA would, at six years almost before 11 they finally approved Fluctin for use in Germany, 12 would tell you right off the bat that they're 13 concerned about suicide, and that one of their 14 concern would be that they're going to require 15 that you use concomitant tranquilizing 16 medications. 17 A. I would not conclude that, 18 because as you see there are a number of issues. 19 Some of them aren't even vaguely related to 20 suicide, one being, for instance, 21 phospholipidosis. 22 Q. We know, Doctor Wernicke, that 23 there was indeed, when Prozac was approved in 24 Germany for Fluctin, a recommendation that for Page 136 1 some patients that they get concomitant 2 tranquilizer, correct? 3 A. Yes, I have heard that, yes. 4 But that does not mean that that's the only 5 reason it took six years as you implied. 6 Q. No, my implication was that 7 the German BGA recognized this as a problem and 8 alerted Lilly that they were going to require 9 concomitant tranquilizer use six years before 10 they approved it, and they never were convinced 11 by Lilly that their position was wrong -- 12 MR. LORE: I object. 13 Q. -- in requiring concomitant 14 tranquilizer use in the package literature for 15 consideration. 16 MR. LORE: I object to the form of the 17 question. 18 MR. SMITH: Okay, fine. 19 A. I can't put myself into the 20 minds of the BGA. 21 Q. It sounds like you've been 22 able to do it so far. 23 A. But that's based on my 24 understanding of the scientific underpinnings, Page 137 1 which is based on the concept that there's this 2 dichotomy of types, and that drugs should treat 3 the agitation portion. It's a fairly fundamental 4 difference and approach to therapy. 5 MR. LORE: Paul, could I take one 6 minute? 7 MR. SMITH: Why don't we just take 8 lunch. If you're going to take a minute, you'll 9 probably take an hour. 10 (A LUNCH RECESS WAS TAKEN.) 11 Q. (BY MR. SMITH) However 12 depressed patients are classified in Germany 13 versus some kind of classification that might be 14 made in the United States, an individual who is 15 suffering from the psychiatric illness of 16 depression is suffering from that disease, 17 whether they be German or American or of some 18 other nationality, is that correct? 19 A. In a large sense, that is 20 correct. 21 Q. In other words, there may be 22 some social consequences of living in a 23 particular country that might mean that there 24 might be a larger or a smaller percentage of Page 138 1 depressed individuals within that country, 2 however a depressed individual is depressed, be 3 he German or American. 4 A. If it's what we call major 5 depressive disorder as defined in this diagnostic 6 and statistical manual -- and the only reason I 7 qualify that is because there are other types of 8 depression, such as bipolar, and it's not always 9 clear that in some systems, those might not be 10 thought of as more of a continuum as opposed to a 11 distinct diagnostic entity. So when you say 12 patients in Germany are depressed and patients in 13 the United States are depressed, that certainly 14 is true, but there may be pqtients that would 15 fall into other categories, so it's not that 16 clear and clearly defined. 17 Q. But if an individual is 18 suffering depression as a result of a biological 19 imbalance in their serotonin system, that 20 individual should have the same biological 21 imbalance be they German or American or Mexican 22 American or of some other national origin. 23 A. That would be correct. 24 Q. And obviously Prozac, Page 139 1 fluoxetine hydrochloride, is marketed in many 2 different countries for treatment of depression. 3 A. Yes. 4 Q. And it's intended that 5 regardless of the nationality of that individual, 6 that individual is going to react biologically 7 and physiologically the same to the molecular 8 compound of fluoxetine hydrochloride. 9 A. Yes, that would be true. 10 Q. I would like to go over with 11 you this letter, point by point, which is Exhibit 12 3, I believe. 13 A. Yes. 14 Q. We'll get back to the BGA's 15 concerns with respect to suicides. The second 16 point of the telex of June, 1984 is that, quote, 17 the BGA states there is a disagreement between 18 patients and the doctor's judgment of efficacy, 19 since in their opinion, the patient's impression 20 is more important. We have to demonstrate 21 correlation between SCL 58 and HAMD, and CGI, and 22 PGI response, paren, perhaps by graphs, question 23 mark, close paren, end quote, correct? 24 A. Yes. Page 140 1 Q. Is what they're saying there 2 that for the German regulatory authorities, that 3 they're interested in what the patient thinks who 4 is involved in the clinical trials concerning 5 whether or not their depression is getting better 6 or worse? 7 A. That would be implied. It 8 suggests that -- whoever wrote this concluded 9 that that's what the BGA is saying. 10 Q. In other words, whether an 11 individual is getting worse or better, in their 12 depressive symptomatology, can be judged in a 13 number of ways. Two ways would be the impression 14 of the patient, I'm feeling less depressed, and 15 the judgment of the physician, he appears to be 16 less depressed, correct? 17 A. Yes. 18 Q. So the German regulatory body 19 feels, according to this memo, that the patient's 20 impressions are most important in concern or in 21 connection with the efficacy of Prozac in 22 alleviating the symptoms of depression. 23 A. What I read in this is that 24 they put relatively more weight on that than Page 141 1 perhaps was in our submission, that they wanted 2 to see more of a correlation. We have the same 3 parameters in our submissions to the FDA, and 4 certainly that's all considered, but what I read 5 as suggested by the author of this telex as to 6 their interpretation of what the BGA wants is 7 more of a one-to-one correlation between these or 8 more heavy weighting on the patient's response 9 rather than just an ancillary piece of 10 information. 11 Q. What it says, what the 12 sentence says is that since in their, meaning the 13 BGA, opinions the patient's impression is more 14 important. 15 A. More important than what? 16 Q. Than the doctor's opinion. 17 A. See, it doesn't really say 18 that. 19 Q. It says what it says, but -- 20 A. Yes. 21 Q. But the complete sentence is 22 the BGA stated that there is a -- there is a 23 disagreement between patient's and doctor's 24 judgment of efficacy, that is where you have a Page 142 1 doctor saying this product is efficacious and the 2 patient disagrees, saying it's not efficacious. 3 The sentence says in their opinion, the patient's 4 impression is more important, doesn't it? 5 A. But important -- more 6 important than the FDA might consider it or more 7 important than the doctor? 8 Q. I read this by saying more 9 important -- the patient's judgment is more 10 important than the doctor's. 11 A. You can, but it doesn't mean 12 that that's what they meant. 13 Q. That's why we have a jury in 14 these cases, Doctor Wernicke, they'll be able to 15 read this and draw their interpretation. 16 MR. LORE: Paul, that's not a 17 question, and he's simply saying what he 18 interprets its meaning, and you have your own 19 interpretation. 20 MR. SMITH: I'm just saying there's 21 probably a third interpretation. 22 MR. LORE: Well, there probably is. 23 A. There may well be, I don't 24 know. Page 143 1 Q. Would you agree with me, 2 Doctor Wernicke, that either of our 3 interpretations is a reasonable interpretation? 4 A. What I would agree with is 5 that the BGA puts relatively more weight on the 6 patient's impression -- 7 Q. All right. 8 A. -- than either the FDA or what 9 the doctor's is, they want to see more of a 10 relationship between the two. That's all I would 11 read into it having not heard directly from the 12 BGA. 13 Q. On that occasion, it wouldn't 14 appear to me that the BGA's opinion in that 15 connection is unreasonable, does it to you, 16 Doctor, to consider the patient's feelings? 17 A. No, I don't think it's 18 unreasonable, I think it's another way to look at 19 it. 20 Q. Of course at this time the 21 Food and Drug Administration hadn't approved the 22 drug, had they? 23 A. That's correct. 24 Q. Did you have any input from Page 144 1 the Food and Drug Administration at this time as 2 to what their feeling was concerning whether or 3 not if there was a disagreement between the 4 patient and the doctor concerning efficacy, that 5 they're going to look to what one or the other 6 might say? 7 A. No. 8 Q. Then where is it that you're 9 saying that the FDA's involved in this at all? 10 A. Because what was submitted to 11 the BGA, as I explained before, was based on what 12 we submitted to the FDA. Now not having heard 13 anything from the FDA, we don't know what their 14 view was on that, but we're not sure -- 15 Q. Did you ever find out what 16 their view was on that? 17 A. We know that they looked at 18 all of that data. I don't remember them coming 19 back and saying we think there should be a closer 20 tie or we think that there should be a one-to-one 21 correlation, but that did not come up as I 22 remember. 23 Q. Do you read this, Doctor 24 Wernicke, that the BGA didn't see a one-to-one Page 145 1 correlation? 2 A. I see this as meaning that 3 there seemed to be some disparity between the 4 scores that the physicians gave on the Hamilton 5 and other factors, perhaps, with what the 6 patients gave. 7 Q. And do you see this as the BGA 8 feeling that the doctors were rating this drug as 9 more efficacious than the patients were? 10 A. I wouldn't limit it to the 11 doctor's opinion. What the major -- the 12 cornerstone of the submission to the FDA, and 13 thereby to the BGA, was the Hamilton Depression 14 Scale numbers. 15 Q. Okay. Do you read it, then, 16 as saying that the patient's representations of 17 how they were feeling didn't correlate with 18 respect to the Hamilton Depression Scale on how 19 it would rate their depression? 20 A. I would agree that there 21 seemed to be some disparity between those. 22 Q. All right. And that that 23 disparity existed because the Hamilton Depression 24 Scale scores were indicating that the patients Page 146 1 were less depressed than the patients were 2 indicating they were. 3 A. I'm not sure I would conclude 4 that because it's not clear whether they're 5 taking about baseline, degree of improvement, 6 it's not quite clear what it is the BGA is 7 focusing on, so it's hard to really comment as to 8 what exactly their question was. 9 Q. Well, I thought you were the 10 one that raised the issue of the cornerstone 11 being the Hamilton Depression Scale ratings, and 12 that it appeared to you that there wasn't a 13 disagreement between the doctor and the patient, 14 it was there wasn't a correlation between the 15 HAMD scores and the patient's impression. 16 A. Yes, but when you rephrased 17 it, you said between the degree of depression. 18 The point I'm trying to make is that the degree 19 of depression, at baseline, before they start, or 20 the improvement. We're talking about a number of 21 different comparisons, and I'm not quite sure -- 22 Q. The word the BGA uses is 23 efficacy, isn't it? 24 A. Yes, but there -- Page 147 1 Q. Doesn't Lilly consider 2 improvement in HAMD scores a demonstration of 3 efficacy of the product? 4 A. Yes, it does, but if you just 5 asked -- when you just rephrased the question, 6 you talked about the Hamilton score, at least I 7 understood it to be, at baseline, as the patients -- 8 how depressed they were, suggesting when they 9 came into the study. I think that's why we're 10 sort of getting off what this question talks 11 about, so I wanted to clarify that. 12 Q. Did you ever call anybody at 13 the BGA or call anybody at Lilly to clarify this 14 point, Doctor Wernicke? 15 A. I don't remember ever seeing 16 this memo. 17 Q. Okay. So you didn't? 18 A. I don't remember doing that 19 because I don't remember this being phrased in 20 this way. 21 Q. Well, in all your work at Eli 22 Lilly and Company, do you ever recall working on 23 this issue raised by the BGA as to some disparity 24 between patients' impressions and HAMD scores, at Page 148 1 any time? 2 A. Not particularly regarding a 3 disparity between scores. 4 Q. I'm talking about the items 5 mentioned in point two here. 6 A. No, I don't remember 7 specifically examining that. 8 Q. All right. Go with me to 9 point seven on page two. Point seven, the first 10 sentence reads the BGA explained their 11 reservations regarding CNS side-effects. There 12 have been a few patients complaining of psychosis 13 and hallucinations, correct? 14 A. Yes. 15 Q. All right. At that time had 16 you ever observed or seen any data to indicate 17 that patients in the clinical trials, either in 18 the United States or outside the United States, 19 were having CNS, central nervous system, side 20 effects in connection with the use of Prozac? 21 A. By this time -- when you say 22 this time, of course I wasn't here at this time. 23 But in the course of development of the drug, we 24 collected reports on all adverse events, without Page 149 1 presumption of causality, and I think that has to 2 be very clear. The way you state the question, 3 as a side effect of the drug, that is not 4 something we conclude in the data-gathering 5 process, that is something we determine as a 6 result of the data-gathering. So when we report 7 and record an event, it is not a statement 8 whether it is or is not a side effect of the 9 drug, and that is a very important point in the 10 gathering and analysis of the data. 11 Q. Okay. Let me stop you a 12 second, Doctor Wernicke. All I'm reading is a 13 sentence that was authored by an Eli Lilly and 14 Company employee -- 15 A. Uh-huh. 16 Q. -- in Germany. 17 A. Yes. 18 Q. All right. He's using that 19 terminology, not me, all right? 20 A. Fine. 21 Q. Let me read that sentence to 22 you again, and would you keep in mind this time 23 that it's a Lilly employee using these terms. It 24 says the BGA explained their reservations Page 150 1 regarding CNS side effects. There have been a 2 few patients complaining of psychosis and 3 hallucinations, end quote, correct? 4 A. Yes. 5 Q. All right. My question to you 6 is, were you aware, once you came on board during 7 this initial start-up process where you were 8 becoming familiar with the status of the Prozac 9 clinical trials, were you aware of any reports of 10 CNS side-effects? 11 A. I was aware of reports of CNS 12 events, but it's the side effects -- well, I know 13 this is what a Lilly person wrote, but remember 14 they're paraphrasing what the BGA said. 15 Q. How do you know that? 16 A. Because it says so right here, 17 the BGA explained their reservations regarding 18 CNS side-effects. So somebody at the BGA said to 19 somebody at Lilly, we think there are CNS side 20 effects, I mean it says that right here, doesn't 21 it? 22 Q. Do you take that that at that 23 time the BGA considered that Prozac produced CNS 24 side effects as a causal relationship with Page 151 1 fluoxetine treatment, is that what you're saying? 2 A. If the person at the BGA 3 stated it in this way, they may have considered 4 that those were side effects caused by the drug, 5 but I don't know that for a fact. 6 Q. Do you know -- do you have 7 anything to dispute whether or not that 8 individual at the BGA would be right or wrong in 9 connection with that statement? 10 A. I think I have a lot to 11 dispute, because I think one cannot know that at 12 that point. And I think if you read the second 13 paragraph, it starts to explain that, that 14 patients may have what's called psychotic 15 depression, which is why I tried to clarify the 16 major depression and bipolar depression. There's 17 another category that's really a subset of 18 psychosis, it's not major depressive disorder, 19 and it probably doesn't involve serotonin, but 20 these patients look depressed, but they may have 21 psychotic episodes, including hallucinations. 22 Q. Okay. Now -- and again, 23 you're not a psychiatrist. 24 A. That's right. Page 152 1 Q. Are we saying there it was 2 well known by you, as a Lilly researcher, that 3 there was an element of psychosis in some 4 depressed individuals that would produce 5 hallucinations that was a co-morbid condition 6 with depression? 7 A. No, that's not correct, it's 8 not a co-morbid condition. And, in fact, the 9 design was that those people should not really 10 have been admitted into this study. But it isn't 11 always very clear, sometimes it only becomes 12 clear in retrospect whether this patient really 13 had psychotic depression or, what we call, 14 unipolar biological depression. So that's always 15 an issue that you have to deal with, is keeping 16 the patient population the one you want to study. 17 But although these patients may look very similar 18 at presentation, the underlying disease process 19 is really quite different, and the treatment is 20 different. People with psychosis should be 21 treated with antipsychotics, not antidepressants. 22 But if you can't tell that for sure, there's no 23 way to make that judgment initially, and you 24 don't treat people with both at once. So it's Page 153 1 easy to second guess in retrospect, but when 2 you're faced with a patient, as the second 3 paragraph suggests, that these may have been 4 patients that had actually a psychotic illness. 5 Q. Are you saying that the Lilly 6 employed investigators who were supposed to be 7 eminent and pre-eminent in their field, are 8 making mistakes and admitting psychotic patients 9 who were supposed to be excluded from the 10 clinical trials into the clinical trials, Doctor 11 Wernicke? 12 MR. LORE: I object to the form, 13 that's not even close to what he's saying, Paul. 14 But if you can answer the question, go ahead. 15 A. Wxat I'm saying is that even -- 16 first of all, medicine is not an exact science, 17 there's no lab test that you can do that says 18 this is psychosis, this is depression, these are 19 clinical judgments. And even the most renowned 20 of experts cannot with every case be absolutely 21 sure, this is just not that exact. 22 Q. Doctor Wernicke, are you of 23 the opinion that Prozac, fluoxetine 24 hydrochloride, does not cause any CNS side Page 154 1 effects? 2 A. No, I'm not of that opinion. 3 Q. What CNS side effects are 4 caused by Prozac? 5 A. We have seen, relative to 6 comparators and placebo, increased rates of 7 insomnia. That's certainly a CNS side effect. 8 Anxiety, nervousness, those were the three, as I 9 remember, that were statistically significantly 10 increased at higher doses. At the twenty 11 milligram -- 12 Q. I'm talking about at 13 therapeutic doses. What were you all doing, did 14 you have the people in your clinical trials on 15 higher doses of Prozac than the patients now 16 taking Prozac are getting? 17 A. Initially, we were, that's how 18 we established the proper dose. 19 Q. Okay. Did you see any CNS 20 side effects of Prozac at twenty milligrams? 21 A. Not statistically, compared to 22 placebo. 23 Q. Did you see any? 24 A. We saw the same statistical Page 155 1 data on placebo -- I mean, yes, we saw some, but 2 we saw some with people taking placebo. 3 Q. Okay. So are you saying, 4 then, that Prozac at twenty milligrams does not 5 produce CNS side effects that are causally 6 related to the Prozac? 7 A. On a group basis, in a 8 statistical comparison, which is really all you 9 can do scientifically, there was no evidence of 10 that. I think that's all one can say, and that's 11 really what we have to deal with. 12 Q. That's what your professional 13 opinion is, that's what your observations are, 14 that's what your experience is, that Prozac at 15 twenty milligrams does not produce any CNS side 16 effects, causally, statistically different, than 17 placebo or comparitors, is that what you're 18 saying? 19 A. At twenty milligrams, there's 20 no statistical significant difference between 21 twenty milligrams and the placebo of the central 22 nervous system effects, as I remember from the 23 studies we did. 24 Q. Could your memory be faulty on Page 156 1 that? 2 A. My memory can be faulty on a 3 number of things. I'm trying to remember the 4 fixed-dose studies, and as I remember, only 5 nausea was significantly higher, and I could be 6 wrong, this is a long time ago and many studies 7 ago. 8 Q. Well, I would point you to 9 every description of Prozac in the Prozac 10 prescribing information in the PDR from the first 11 time it was ever approved, it's always had a 12 chart in it that listed the clinical trial 13 experience that listed CNS side effects, hasn't 14 it? 15 A. Yes. 16 Q. All right. 17 A. And there's a column for 18 placebo, too. 19 Q. Right. 20 A. Yes. 21 Q. And there was a greater rate 22 of reports of CNS side effects in the fluoxetine 23 group than in the placebo group, wasn't there? 24 A. But was that statistically Page 157 1 significant, greater -- just because it was 2 numerically greater, that doesn't mean it was 3 significant, and that's what I don't remember 4 what the P value was. 5 Q. I think it was reflected in 6 percentages, Doctor Wernicke. 7 A. I know, but that's not the 8 same. If one is nine percent and one is ten 9 percent, is that truly greater? That's why we -- 10 Q. What if something is fifteen 11 percent and something is three percent, is that 12 significantly greater? 13 A. It may not. That's the 14 problem, you have to look at it in the context of 15 variants. There are a number of things that go 16 into a statistical comparison, and this is done 17 for a reason, it's to take away the subjective 18 gut feeling from it. There are mathematical 19 principles applied across science, not just in 20 the pharmaceutical industry, that test the rates 21 in two populations in a totally objective, 22 unbiased way. That's why we use statistics. 23 Q. Okay. Does that mean that 24 Prozac at twenty milligram couldn't cause CNS Page 158 1 side effects in a particular patient? 2 A. One cannot draw conclusions 3 about individual patients from a population like 4 that, it's a totally -- it's sort of an 5 irrelevant question because you can only -- you 6 can look at it scientifically on a population 7 basis, it really has no relevance to the question 8 of an individual. Whether it can or can't, it's 9 sort of a meaningless question. There's no -- 10 scientific understanding is based on population 11 studies in this context, and it's improper and 12 incorrect to make conclusions one way or the 13 other about anything beyond that. 14 Q. Well, are you saying that what 15 might happen to one particular individual using 16 Prozac is immaterial or irrelevant? 17 A. No, I'm not saying that at 18 all. All I'm saying is what learn -- what we do -- 19 the only thing we can do in the context of 20 developing a drug and understanding it is to look 21 at the overall population, and to understand that 22 in reference to a comparator population, be it 23 placebo, other drug, or whatever. That doesn't 24 mean it's immaterial, it's just that we can't Page 159 1 discern that except in the context of what I 2 explained before, with a rechallenge type of 3 situation. 4 Q. I want to go back to something 5 else you said earlier. Are you saying that 6 there's three, now, types of depressed 7 individuals, there's individuals who are agitated 8 depressed, retarded depressed, and now psychotic 9 depressed? 10 A. Well, actually it's more 11 complicated than that. There's also a group that -- 12 there are three recognized illnesses, at least 13 three major ones that people can appear 14 depressed, and one is psychotic depression, the 15 depressive element of psychosis. The other one 16 is bipolar depression. The two that you 17 mentioned, agitated, retarded, really fits into 18 one category, what we call unipolar depression. 19 So if you want to say there's three big ones, and 20 under those there are two subgroups in the 21 unipolar. But even in those, there are 22 permutations and variations. That's why this is 23 a very complicated and not totally agreed to 24 principle, it's not always clear which group one Page 160 1 patient falls into and what patient falls into 2 another group. 3 Q. Are you saying that these 4 individuals may react differently with 5 antidepressive treatment? 6 A. I would say that that's 7 probably true. 8 Q. Okay. And would those 9 differences on occasion be marked? 10 A. Well, it certainly would be 11 marked in the sense that if a patient was 12 psychotic and what they really needed was an 13 antipsychotic medication, when one treated them 14 with an antidepressant they wouldn't be likely to 15 get a beneficial effect. And that certainly is a 16 marked difference. 17 Q. All right. 18 A. So treating somebody with a 19 wrong antibiotic -- 20 Q. Does an ordinary general 21 practitioner know about these distinctions? 22 A. Certainly the psychiatrists 23 do. 24 Q. No, that's not what I asked Page 161 1 you, Doctor Wernicke, I specifically said the 2 ordinary general practitioner. Don't turn my 3 questions around on me, please answer my 4 questions directly. I'm not giving you these 5 questions off the top of my head, for no reason, 6 I'm specifically asking you specific questions. 7 My question is, does the ordinary general 8 practitioner know about these distinctions? 9 A. I was not trained in that area 10 and I'm not prepared to answer that. 11 Q. You don't know? 12 A. I don't know. 13 Q. Can you diagnose psychotic 14 depression in an individual, as a neurologist? 15 A. I would not really feel 16 comfortable doing that. 17 Q. Can you diagnose bipolar 18 depression in an individual? 19 A. With the proper history, I 20 would feel quite a degree of confidence that I 21 could probably make that diagnosis. 22 Q. Can you diagnose unipolar 23 depression within an individual? 24 A. Again, with a good history, I Page 162 1 would feel relatively confident, but I would 2 never quite go so far as to make that diagnosis 3 because I'm not a psychiatrist. 4 Q. Would you be comfortable in 5 distinguishing whether or not a patient is 6 suffering from unipolar versus psychotic 7 depression? 8 A. Not in every case. 9 Q. Would you, in every case, be 10 comfortable in making a distinction whether or 11 not a patient is suffering from bipolar versus 12 unipolar depression? 13 A. No, not in every case. 14 Q. Would you, in every case, be 15 able to make a distinction between an individual 16 suffering from psychotic depression and agitated 17 unipolar depression? 18 A. I'm not sure I could in every 19 case. 20 Q. Do you think a general 21 practitioner would be better able to make these 22 distinctions than yourself, sir? 23 A. Again, I really don't know, I 24 would have to know what that general Page 163 1 practitioner's training was. This is not -- 2 Q. Let's assume he's had the same 3 training that you've had without your neurology 4 specialty. 5 A. Well -- 6 Q. And, again, you've had more 7 experience with antidepressant treatment than the 8 ordinary general practitioner, haven't you? 9 A. Not on a patient-by-patient 10 basis. In the context of looking at the data, 11 but not experience in seeing patients and 12 treating them, no. 13 Q. But you've been to psychiatric 14 conventions all the way across the ocean in 15 Germany, haven't you? 16 A. Yes. 17 Q. And you've talked to 18 investigators worldwide who are theoretically 19 knowledgable concerning these issues, haven't 20 you? 21 A. Yes. 22 Q. You've talked to Doctor Stuart 23 Montgomery. 24 A. Yes. Page 164 1 Q. An authority in England. 2 A. Yes. 3 Q. Lilly feels that they have 4 some of the best psychiatrists in the country on 5 staff in their facility there in Indianapolis, 6 don't they? 7 A. I don't know what they think 8 about that. 9 Q. Well, I've heard Doctor Mel 10 Perelman refer to Doctor Charles Beasley as a 11 very qualified psychiatrist. Do you dispute 12 that? 13 A. I don't dispute that. 14 Q. Okay. An individual such as 15 yourself, is it your testimony that you have any 16 better ability to distinguish between these 17 various depressive states that you've stated in 18 treatment of these individuals than the ordinary 19 general practitioner? 20 MR. LORE: Object to the form of the 21 question, calls to ask him to speculate as to 22 what a general practitioner would know or not 23 know. 24 Q. Well, when you were the Page 165 1 clinical trial monitor for Prozac, responsible 2 for the U.S. clinical trials, didn't you make 3 yourself reasonably aware of what general 4 practitioners in the United States knew or didn't 5 know about psychiatry and antidepressive 6 treatment, Doctor Wernicke? 7 A. No, that was wasn't really a 8 large part of what I was involved in. 9 Q. Who there at Lilly was keeping 10 abreast of what general practitioners knew about 11 antidepressant treatment? 12 A. The only thing I know in 13 regards to that is that some of the marketing 14 people felt that it was important that physicians 15 in general learn more about depression. 16 Q. Okay. So there was a feeling 17 at Lilly that physicians in general, including 18 general practitioners, be better able to 19 recognize the mental illness of depression, 20 correct? 21 A. That's correct. 22 Q. Now, what did they do about 23 knowing whether or not the general practitioner 24 was adequately trained in the administration of Page 166 1 antidepressant medication? 2 A. I don't know what they did to 3 ascertain that. 4 Q. Did you do any -- or while you 5 were at Eli Lilly, did you do any studies to look 6 at prescribing practices of general practitioners 7 in connection with antidepressant medication? 8 A. I was not involved in any such 9 studies. 10 Q. Were you aware of what courses 11 in pharmacology, psychiatry and neurology were 12 being offered in medical schools in the United 13 States to give general practitioners and 14 physicians at large a basic understanding of the 15 anatomy of the human brain and pharmacology of 16 psychotropic medications? 17 A. I'm aware of the courses that 18 I took in medical school. 19 Q. Was there anybody there at 20 Lilly that was looking at what the educational 21 level of physicians in the United States was in 22 these subjects? 23 A. I'm not aware of any such 24 person. Page 167 1 Q. Wasn't the assumption that 2 general practitioners weren't recognizing 3 depressive illnesses as they should have? 4 A. It was not stated as an 5 assumption. An assumption is a personal thing, 6 there was no memo that said we, Lilly, assume 7 that general practitioners don't recognize 8 depression, I'm not aware of any -- 9 Q. Then why was there an effort 10 being made, sir, to make general practitioners 11 more aware of depressive illnesses? 12 A. I was not involved at all 13 levels of the planning and strategy for the 14 evolution of this drug. 15 Q. You were the one that brought 16 it up concerning the fact that there were 17 marketing plans to make the general practitioner 18 more qware, or physician in general I think is 19 what you said, more aware of depressive 20 illnesses. 21 A. I didn't say that there were 22 plans to make them more aware, I said that there 23 were discussions in consideration of the idea 24 that perhaps the general practitioner was not as Page 168 1 aware. That doesn't go so far as to say there 2 were definite plans to do that. 3 Q. Okay. Well, was there 4 anything done about this or following these 5 discussions at Lilly concerning the fact that 6 general practitioners weren't aware of depressive 7 illnesses as they should be? 8 A. The things that I know that 9 were done, and I'm not sure of all the reasons 10 behind this, is there were original symposia 11 where general practitioners were invited and 12 psychiatrists would speak about depression. 13 Q. Do you know whether they were, 14 these fellows that were psychiatrists that were 15 educating these general practitioners, whether 16 they were being paid out of the marketing budget 17 or the clinical trial budget for Prozac? 18 A. They were not paid from the 19 clinical trial budget if they were not 20 investigators for a study. Where they were paid 21 from, beyond that I don't know. 22 Q. Was there a part of this 23 course that explained the differences between 24 psychotic depression, bipolar depression and the Page 169 1 nuances of agitated and retarded depression that 2 exist in unipolar depression? 3 A. I don't know, because I never 4 was that closely involved with these lectures and 5 courses. 6 Q. And you've said you don't 7 really feel comfortable in diagnosing the nuances 8 among these depressive illnesses yourself? 9 A. I would not feel comfortable 10 to the point where I would prescribe a 11 medication, just because I'm not a psychiatrist. 12 This is a fairly profound decision, and I would 13 want to have somebody with more experience 14 involved. But I feel if I took a history and the 15 history were clear, I would feel quite confident 16 I could make the right diagnosis. 17 Q. But then you would leave it to 18 a psychiatrist to treat that individual? 19 A. Or somebody that was more 20 versed and more experienced. When I say my 21 experience is looking at the data, looking at 22 large collections of data and analyzing it, 23 that's quite different than the day-to-day 24 experience of dealing with patients, of making Page 170 1 the diagnosis. You can have a lot of knowledge 2 from one end of the therapy and relatively little 3 from another, and that's sort of the situation I 4 was in. 5 Q. So you, yourself, feel that 6 you could diagnose in general, in most 7 individuals, a depressive illness, correct? 8 A. I would say that, yes. 9 Q. But you would refer those 10 individuals, once you'd made that diagnosis, to a 11 psychiatrist? 12 A. Or some other physician that 13 was used to or experienced in dealing with these 14 kinds of disorders, not necessarily a 15 psychiatrist. 16 Q. If it's not necessarily a 17 psychiatrist, what kind of experience would you 18 require for treatment of a loved one that you 19 felt was depressed? 20 A. That physician's experience -- 21 that physician's experience in that disorder. 22 Q. Experienced in depression? 23 A. Well, in psychiatry or in 24 psychiatric disorders. Page 171 1 Q. All right. And then you would 2 leave that -- the decision of what antidepressant 3 therapy, if any, to that individual experienced 4 in treatment of depressive disorders for a loved 5 one of yours? 6 A. In general. I certainly would 7 be more involved than if I weren't a physician, I 8 would certainly want to know what they were doing 9 and why. But I think in general it's not a good 10 practice for people on the large scale to treat 11 their own families for a serious disorder. 12 Q. I'm not suggesting that, I'm 13 just suggesting that for me, for my wife, if she 14 was depressed, would you recommend that I send 15 her to an individual experienced in treating 16 depressed individuals? 17 A. I would recommend that that 18 person have some experience; it doesn't have to 19 be a Board certified professor of psychiatry. 20 But I think, yes, as with every disease, if you 21 had a serious pneumonia I wouldn't send you to an 22 orthopedic doctor, I think you should see 23 somebody that has experience. They may not have 24 to be a pulmonologist, but you want somebody with Page 172 1 hands-on experience and a sense of what these 2 patients are like and what these medications are 3 like. 4 Q. All right. And you would want 5 somebody experienced in administering 6 antidepressant medication to make the selection 7 of the particular -- or make the decision, number 8 one, whether or not antidepressive medication 9 would be appropriate, correct? 10 A. Yes, I would agree with that. 11 Q. And number two, you would want 12 somebody with some experience making the decision 13 in connection with what particular antidepressant 14 treatment should be given? 15 A. Yes, I think that would be 16 correct. 17 Q. And leave to someone -- dosage 18 questions to somebody that's experienced? 19 A. Well, the dosage is a little 20 bit different because that has to be taken in the 21 context of what the recommended dose is, and that 22 there the practitioner has to rely fairly heavily 23 on what's been learned and what's in the 24 literature and the package insert. So, for Page 173 1 instance, if somebody was very experienced in 2 psychiatry and had seen a lot of these patients 3 but had an idea that they should use ten times 4 the recommended dose, I would approach that with 5 caution. 6 Q. Yes, I'm talking about making 7 dosage selections within dosage recommendations 8 of the manufacturer. 9 A. Yes, then I would leave that 10 to them, yes. 11 Q. Because there are varying 12 dosages that are applicable for Prozac, are there 13 not? 14 A. There's only one recommended 15 dose for depression and that's twenty milligrams, 16 as far as I know, and I believe that's still the 17 case unless there's been a recent change. I 18 haven't looked at the package insert in a long 19 time. 20 Q. The package insert also says 21 it can be given up to eighty milligrams in the 22 discretion of the physician. 23 A. Right, but that's not the 24 recommended dose, starting dose is still twenty. Page 174 1 The eighty comes from that's a large range that 2 we had safety data, that it had been used up to 3 the doses. That was just to give people a 4 guideline to where we felt comfortable that there 5 wouldn't be a safety issue. 6 Q. I understand. But -- 7 A. But that's different than a 8 recommended dose. 9 Q. The physician is allowed some 10 discretion within the twenty to eighty 11 milligrams. 12 A. Yes. 13 Q. With respect to Prozac. 14 A. Actually they're allowed 15 complete discretion, that's the manufacturer's 16 recommendation. 17 Q. All right. And while we're on 18 that, just in passing, we'll talk about it in 19 more detail later, but Lilly's still not 20 determined the lowest efficacious dosage, have 21 they, of Prozac? 22 A. When I was there, and as far 23 as I know that still holds true, the lowest 24 generally efficacious dose was determined to be Page 175 1 twenty. And the reason I qualified it that way 2 is because there are some individuals that may 3 respond to a lower dose. But just as one can't 4 assess adverse events or side effects on a 5 case-by-case basis very accurately, it's not 6 appropriate to say well, this patient responded 7 at five or ten, they may have responded at two, 8 and that does not extrapolate to the entire 9 population. One has to come up with a statement 10 that this is the best dose for the population in 11 general, as far as we can tell, and that was 12 twenty and still is twenty as far as I know. 13 Q. But do you know it's now 14 manufactured in ten milligram solid pulvule? 15 A. Yes, and also a liquid, I 16 understand. 17 Q. Well, it's always been 18 manufactured as a liquid or shortly after. 19 A. Shortly after, yes. 20 Q. All right. Let's go back to 21 item seven in Exhibit 3. It says the BGA 22 explained their reservations regarding CNS side 23 affects. There have been a few patients 24 complaining of psychosis and hallucinations. Page 176 1 Please provide us with detailed reports whether 2 these patients suffered from psychotic 3 depression, whether the hallucinations developed 4 during treatment or have perhaps been present 5 already at start of treatment or whether these 6 events may indeed be interpreted by aggravation 7 of disease, end quote, correct? 8 A. Yes. 9 Q. And they use the term 10 aggravation of disease in quotations, do they 11 not? 12 A. Yes. 13 Q. Do you have any idea why they 14 would use that term in quotations? 15 A. I can't say that I know why 16 they would have done that. 17 Q. Have you heard the term 18 aggravation of disease? 19 A. Well, yes, as meaning 20 worsening of the disease, deterioration. 21 Q. Will some medications make 22 some disease processes worse? I'm talking about 23 in the general sense. 24 A. Yes, it can happen. It's Page 177 1 uncommon, but there are cases of that. 2 Q. Well, if I have avascular 3 necrosis and I take high levels of steriods, I 4 could make my avascular necrosis far worse, 5 couldn't I? 6 A. Yes, but by a different 7 mechanism. For example, what I'm thinking of is 8 anticonvulsants, that I'm quite familiar with. 9 If you take them in very high doses, sometimes 10 that can precipitate seizures. But that's the 11 best example I know. 12 Q. Because you're a neurologist 13 and there may be a lot of examples. 14 A. Yes, but that's the one I sort 15 of know about. 16 Q. Is what they're expressing 17 here, that if the event of hallucination and 18 psychosis occurred during treatment and had not 19 existed, as far as the investigator knew, prior 20 to treatment, that there was some concern that 21 Prozac may be aggravating the disease of 22 psychotic depression? 23 A. I'm not sure that I read any 24 concern like that. I think what this is is like Page 178 1 the deaths and suicides, these events occurred, 2 we want to know more. And what motivated that 3 question is impossible to say in the minds of the 4 people at the BGA. 5 Q. Well, of course it's in the 6 paragraph concerning CNS side effects, isn't it? 7 A. Yes. 8 Q. And it's talking about 9 specifically psychotic depression, isn't it? 10 A. And hallucinations, yes, and 11 psychosis. 12 Q. Is hallucinations a product of 13 psychotic depression or is that a different 14 symptom? 15 A. It's a part of psychosis, of 16 which depression and hallucinations are both 17 symptoms. 18 Q. All right. And aren't they 19 talking about the hallucinations occurring after 20 drug treatment as being aggravation of the 21 psychotic depression, aggravated by the drug? 22 MR. LORE: I object to the form of the 23 question, Doctor Wernicke's already answered 24 that. He neither wrote this memo and neither Page 179 1 received it, and he's told you what it says. You 2 have asked him for his interpretation, and he's 3 given that to you, I don't know how he can go any 4 further. 5 Q. You can answer that. 6 A. Would you restate the 7 question, I've forgotten exactly what the gist of 8 the question was. 9 MR. SMITH: I'll have it read back, 10 and you can have your same objection. 11 MR. LORE: Thank you. 12 (THE COURT REPORTER READ BACK THE 13 REQUESTED TESTIMONY.) 14 A. Should I comment? 15 MR. LORE: If you can answer. I might 16 add that I can't understand it, but -- 17 A. It's sort of one of the 18 possible scenarios. It's not suggested that that 19 is the mechanism, what they're saying is here's 20 some observations, psychosis, psychotic episodes 21 and hallucinations. Now here are three different 22 things that could cause that, do you have any 23 information to help us sort it out. That's what 24 I read into it and I think that's what it means. Page 180 1 Q. Do those questions appear to 2 be reasonable on your part, Doctor Wernicke? 3 A. Yes, absolutely. 4 Q. In fact, do you view any of 5 these questions raised by the BGA as trivial? 6 A. Only in hindsight. I think at 7 that time they were all -- well, I have to read 8 the whole thing over again, but -- 9 Q. Generally speaking. 10 A. General speaking, I think 11 they're all reasonable questions. 12 Q. This is not just nit-picking 13 regulators, is it? 14 A. No, no, I agree, these are 15 appropriate, reasonable questions that we have 16 dealt with appropriately and reasonably. 17 Q. Well, I don't agree with that, 18 but we'll -- 19 A. The BGA -- 20 MR. LORE: That's not a question, 21 that's just a comment from Mr. Smith. 22 A. The BGA approved the drug, so 23 apparently the BGA thought -- they did approve 24 the drug, so apparently they thought the Page 181 1 questions were answered. 2 Q. Well, did you know the BGA 3 approved the drug with the requirement that 4 concomitant sedative medication be used in cases 5 of excitability and care should be issued in 6 using this drug with individuals who are 7 suicidal? 8 MR. LORE: I object to the form of the 9 question. 10 Q. To be honest, did you know 11 that? 12 A. I had heard that. I don't 13 know if those are the exact words. 14 MR. LORE: They are not. 15 Q. We'll get the exact words. 16 Item ten here says comparative use of 17 concomitantly taken hypnotics and benzodiazepines 18 in agitated retarded fluoxetine patients versus 19 agitated retarded patients on comparitors. 20 Reason, the BGA suspects fluoxetine to be a 21 stimulating activating drug. Side effect profile 22 suicides, suicide attempts, end quote, correct? 23 A. Yes, uh-huh. 24 Q. Were individuals given Page 182 1 concomitant benzodiazepines during the Prozac 2 clinical trials? 3 A. It was allowed. It was not 4 systematically done, but it was something 5 investigators were allowed to do under the 6 protocol. 7 Q. That's not what my question 8 was, listen to my question, Doctor Wernicke. 9 Were benzodiazepines, Valiums, for instance, 10 tranquilizers, given to patients in the Prozac 11 clinical trials? 12 A. To some patients. 13 Q. All right. 14 A. If it's more than one, the 15 answer is yes. 16 Q. You don't know how many 17 patients were given benzodiazepines, Doctor 18 Wernicke? 19 A. I don't know the exact number, 20 but I do remember a comparison we did to look at 21 the benzodiazepine use between the different 22 drugs, including the sedating tricyclics and 23 placebo, and in fact the use of benzodiazepines 24 was not different than all of those groups. Page 183 1 Q. It's your testimony here that 2 benzodiazepines were given at the same rate to 3 patients within the fluoxetine group as they were 4 to patients on placebo and comparitors? 5 A. In the comparison that I 6 remember, there was no statistical difference 7 between the use in those three groups. I'm not 8 talking about the absolute number, I'm talking 9 about the statistical comparison to look at the 10 use of these drugs in the analysis that I was 11 involved in. 12 Q. Did you make such an analysis? 13 A. Yes, I remember being involved 14 in that. 15 Q. Why did you make such an 16 analysis? 17 A. To look at this issue of is 18 the drug activating, is it sedating, how sedating 19 is it, should benzodiazepines be used. So we 20 asked the question, in fact, let's see what 21 people are doing. And this was at relatively 22 free use, investigators were allowed to use these 23 drugs at their discretion. So we asked the 24 question, we have thoughts like this that maybe Page 184 1 these people should have a sedating drug or maybe 2 they need it, because this is not a sedating 3 drug. 4 Q. Prozac is not a sedating drug? 5 A. It's not a sedating drug. 6 Q. We got that, all right. 7 There's not going to be any dispute in your 8 testimony. Prozac, in your opinion, is not a 9 sedating drug, okay? 10 A. In an overall sense, no. 11 There are individual patients that do report 12 sedation on Prozac. Remember, in making this 13 leap from the overall data base to every 14 individual case, there are certainly reports of 15 sedation. But we did not consider it a sedating 16 drug, per se. 17 Q. Generally speaking, Prozac is 18 not a sedating drug. True statement? 19 A. That's a true statement to my 20 knowledge. 21 Q. Go ahead, I interrupted you 22 and I apologize. 23 A. We were talking about why we 24 looked at the use of benzodiazepines, and it was Page 185 1 to get at the truth of what was really happening 2 because it was not felt to be sedating, and we 3 knew some people had agitation as a part of their 4 depression and we knew that Prozac did not have 5 an effect of making them sleepy or suppressing 6 that and we wondered whether people were in fact 7 requiring the use of a sedative, and we found in 8 the analysis that I remember that there really 9 was no increased use. 10 Q. Okay. Then I need to know 11 when that analysis was done? 12 A. Somewhere in '85, '84 to '86 13 time frame, that's as best as I can. 14 Q. Was this a clinical trial that 15 was done? 16 A. No, we looked at all the 17 clinical trial data. We looked -- we gathered 18 all the information and we actually looked at the 19 drug use that was reported in the clinical 20 trials. 21 Q. So it's your testimony here 22 that you all examined each clinical trial and you 23 looked back at each depression clinical trial and 24 you recorded how many patients and what patients Page 186 1 got tranquilizers, is that right? 2 A. We looked at the comparator 3 trials. There were some that did not involve 4 comparators, so there was nothing to compare to, 5 so those were probably not included in the 6 analysis. 7 Q. Okay. So when you say 8 comparator trials, do you mean you looked at all 9 trials where we use placebo or we used a drug 10 like imipramine, or some other antidepressant, as 11 the comparator drug? 12 A. When you say all trials, I'm 13 not sure that every single trial was used. We 14 looked at what our data base was and what we were 15 using for comparisons, which was mainly the 16 fluoxetine, imipramine, placebo study. 17 Q. Well, didn't your data base 18 include all your clinical trials, Doctor 19 Wernicke? 20 A. Well, it didn't include some 21 of the European clinical trials, those were 22 handled separately because they were not in the 23 same data base. 24 Q. What data base were they on? Page 187 1 A. Something they kept in Europe, 2 I was not closely involved in that. But the U.S. 3 trials, we had a large data base. And when I say 4 not all of the trials, there may have been very 5 early ones that for some reason or another may 6 not have been included. But the way we tried to 7 answer these questions, this, like many others 8 that have nothing to do with any of this, is we 9 had a large block of data that was -- we 10 understood the data, we knew where it came from, 11 we felt comfortable it was all correct. 12 Q. Liked it? 13 A. It was usable data. 14 Q. Okay. 15 A. And we used that in the form 16 of the analysis. 17 Q. Uh-huh. 18 A. As to answer these questions. 19 And to keep -- to be consistent, we tried to 20 always stay with the same data base unless there 21 was some particular question we had to go 22 somewhere else. 23 Q. See, I need to know what was 24 in that data base in connection with -- you say Page 188 1 well, we examined our clinical trial data and we 2 looked at this issue and found that there wasn't 3 any problem, but I want to go back with you and I 4 want to make sure that you define for me what 5 you're talking about. 6 A. Okay. 7 Q. Are you talking -- are you 8 saying you revisited all your depression clinical 9 trials? 10 A. I wouldn't say revisited, 11 there was ongoing analysis on a number of 12 different issues. 13 Q. Here the issue is, were 14 benzodiazepines, tranquilizers, used in the 15 clinical trials, and if so, to what extent were 16 they used, what patients got tranquilizers, when 17 did they get them, and why did they get them. 18 Are those reasonable questions? 19 A. Those are reasonable 20 questions. 21 Q. All right. So what did you 22 do, did you look at all the United States 23 clinical trials? 24 A. We looked at the ones, the Page 189 1 major ones, certainly, where there was a 2 comparator. 3 Q. Okay. When you say major 4 ones, that tells me that there may have been some 5 minor ones that might have some data that would 6 be relevant, Doctor Wernicke. 7 A. I understand what you're 8 saying, and what I'm saying is that that is 9 potentially true, I just don't remember whether 10 five or ten years ago we included, or whether 11 every trial had been included in that data base 12 because we didn't sort of define this in relation 13 to the particular question we wanted. It had -- 14 if we needed comparative data, we looked at this 15 block that included the fluoxetine, imipramine, 16 placebo study, there was an amitriptyline 17 controlled study, those are the major ones. If 18 we wanted to look at all safety data, we put in 19 every fluoxetine exposure. If we wanted to look 20 at something compared to placebo, we only looked 21 at placebo studies. I mean you have to do that, 22 and it's relevant to the question you have, what 23 data base or what subset of the data you look at. 24 Q. Yes, that's the reason I'm Page 190 1 asking, because it is relevant. Because you 2 ended up saying from a statistical standpoint, 3 there wasn't any difference in the tranquilizers 4 given to Prozac patients versus other patients. 5 Is that what the conclusion was? 6 A. That's right. 7 Q. I want to back-up from there. 8 Number one, I have not seen any written report on 9 this analysis. Was there such a written report 10 made as far as you know, would this have been 11 something that was reduced to writing in some 12 manner? 13 A. I'm almost certain it was 14 included with the BGA response because that was 15 part of what we did to look at that issue. 16 Q. When? 17 A. That would have been '84 to 18 '85, sometime in that time frame. That's as 19 close -- there were a lot of things going on in a 20 lot of areas. 21 Q. We're talking about 22 concomitant tranquilizer medications. 23 A. I know, but I was doing other 24 things, too, so I can't say that this was in this Page 191 1 month. 2 Q. But you, in your mind's eye, 3 can see a report, something written, some product 4 of this investigation, as to whether or not there 5 was concomitant tranquilizers being given in the 6 clinical trials and an analysis made of who got 7 the concomitant tranquilizers, when, how much, 8 and where? 9 A. I remember the table looking 10 at the rate of use, the percent of patients that 11 used it, and -- 12 Q. A table looking at rate of 13 use? 14 A. The frequency of use in the 15 different groups, fluoxetine, tricyclic drugs and 16 placebo. Now when those were used, I don't 17 remember whether we looked at that, and certainly 18 who used them, I don't remember a list of 19 individual patients. 20 Q. Do you remember an analysis of 21 a, quote, pure pool set of individuals who had 22 not received any concomitant medications -- 23 A. Yes. 24 Q. -- and basing some type of Page 192 1 conclusion based on that data? 2 A. Yes, I remember that now, and 3 that was in response to an FDA question. 4 Q. Response to an FDA question? 5 A. Yes. 6 Q. What was the FDA question that 7 was raised at that time? 8 A. They wanted -- it wasn't 9 phrased in terms of a question. They said look, 10 some of these people are taking psychotropic 11 drugs, and it's hard to really sort out what's 12 doing what, so we would like you to analyze, what 13 we call a pure pool, and that's patients who 14 weren't taking anything else, no psychotropic 15 drugs. 16 Q. Uh-huh. 17 A. And the conclusion was that 18 the profile of efficacy was the same, that it 19 didn't matter. 20 Q. Whether they were on 21 concomitant tranquilizers or they didn't have 22 anything? 23 A. Right, that didn't affect -- 24 Q. In connection with efficacy, Page 193 1 you're saying? 2 A. Efficacy. 3 Q. How about safety? 4 A. I don't remember us looking at 5 that. I believe the issue was mostly is efficacy 6 being affected. 7 Q. Wouldn't it be a consideration 8 of safety, too? 9 A. I don't know what the FDA's 10 thinking was or what exactly prompted that. I 11 remember the analysis being done and the 12 statement being made that it didn't seem to 13 affect the outcome or didn't affect the outcome. 14 Q. You mean the efficacy outcome? 15 A. Right. But I don't remember 16 any analysis or consideration or even looking at 17 the safety. It may or may not have been, I just 18 don't remember that. 19 Q. Okay. Let's back-up, back to 20 concomitant medications and tranquilizers, right? 21 A. Yes. 22 Q. You're with me? 23 A. Yes. 24 Q. Okay. And you say there was Page 194 1 some analysis made of what patients were 2 receiving concomitant medications, and the 3 conclusion was that patients were getting 4 concomitant medications almost equally across 5 treatment groups? 6 A. Yes. That was my memory of 7 that investigation. 8 Q. Okay. Then you say there is a 9 document reflective of that investigation? 10 A. I know we incorporated that 11 information into a submission, but to the best of 12 my knowledge, that was in response to the BGA. 13 But beyond that -- it could have also been to 14 another regulatory agency, but I'm fairly certain 15 it was to the BGA. 16 Q. This issue of activation 17 wasn't raised just by the BGA, was it? 18 A. I don't remember any other 19 government body phrasing it in terms of agitation 20 or activation. 21 Q. How about England, the CSM, 22 expressing almost exactly the same concern that 23 this product may be activating? 24 A. The reason it's hard to Page 195 1 remember is because a lot of these things were 2 going on in parallel, and when we did the 3 analysis, I'm not sure -- I don't remember now 4 where the question originated from, and sometimes 5 we used the same analysis to respond to several 6 agencies, there was quite a bit of overlap, so I 7 can't say for certain. I don't remember a 8 specific list of questions from the CSM related 9 to that. 10 Q. But there could have been? 11 A. There certainly could have 12 been. 13 Q. Do you remember the FDA ever 14 raising this issue, Doctor Wernicke, as to 15 whether or not Prozac was an activating 16 medication? 17 A. I remember questions and 18 discussions about the CNS profile of events. 19 Whether they used the words agitation or 20 activating, I don't remember that specifically, 21 but I remember we did look at those -- that group 22 of events with the FDA. 23 Q. So the FDA was looking at it 24 in terms of a CNS profile? Page 196 1 A. Well, the whole side effect 2 profile. They were looking at rash and 3 everything, they look at everything, by 4 everything. That's the way they do it, that's 5 their job. 6 Q. As it was the BGA's job in 7 Germany? 8 A. That's right. 9 Q. And as it was the CSM's job in 10 England? 11 A. Correct. 12 Q. As was the whatever it is in 13 France, correct? 14 A. Yes. 15 Q. And all four of those 16 countries could raise valid scientific questions 17 concerning the safety of Prozac, couldn't they? 18 A. Yes. 19 Q. Any one of those four could be 20 wrong and any one of those four could be right, 21 correct? 22 A. When you raise a question -- 23 they didn't make statements, they raised 24 questions, so it's not a matter of being right or Page 197 1 wrong, they asked a question, that does not imply 2 that they had an opinion. 3 Q. All right. Well, and we can 4 say concerning opinions, we can say that in June 5 of 1984 the BGA, in fact, or Lilly employees were 6 using terms like the BGA suspects fluoxetine to 7 be a stimulating activating drug, side effect 8 profile, suicides and suicide attempts, correct? 9 A. That's what this memo says 10 from this employee, yes. 11 Q. Do you have any reason to 12 believe that this employee is misrepresenting 13 what the BGA's opinions and questions and 14 feelings were in June of 1984, Doctor Wernicke? 15 A. Since I don't know what 16 interaction these people had with the BGA, 17 whether they sat across the table, whether this 18 was expressed, whether this was an interpretation 19 of what the BGA had written, there was a lot that 20 I wasn't involved in, so it's very hard for me to 21 reconstruct what was in their minds, and even 22 more, what was in the BGA's mind. 23 Q. Do you know Doctor Schenk? 24 A. Yes. Page 198 1 Q. Do you know Doctor Weber? 2 A. Yes. 3 Q. Do you respect those 4 individuals? 5 A. Yes. 6 Q. Are they relatively 7 intelligent individuals? 8 A. They seem to be. 9 Q. Do they seem to have had ever 10 any difficulty in communicating thoughts and 11 ideas of others to Indianapolis, Indiana? 12 A. Well, since I don't know the 13 thoughts of others, that's hard to make a 14 judgment on. 15 Q. Were they in any way less than 16 articulate, Doctor Wernicke? 17 A. I think in some instances they 18 used words that wasn't always clear to us what 19 was meant. 20 Q. Did you ever call and say 21 look, this English word you're using is a little 22 unclear, give me the German word since I speak 23 German? 24 A. We discussed some of these Page 199 1 things -- I'm trying to remember what the words 2 they used. There was an interpretation question 3 that we finally decided was a retarded 4 depression. There's a German word that really 5 doesn't have an English equivalent, and there was 6 quite a bit of back and forth about what do they 7 really mean, and the best we came up with was a 8 retarded depression or melancholia, which is sort 9 of a subtype that's not really used anymore. So 10 there were some miscommunications of language 11 that were not related to their inability or lack 12 of intelligence or anything else, it's just sort 13 of a nuance of language and the way they looked 14 at psychiatric disorders. 15 Q. Did you ever look at this or 16 did you ever go back and discuss these issues 17 with Doctor Weber or Doctor Schenk and recall any 18 miscommunications in this June, 1984 memo? 19 A. I've never seen this June, 20 1984 memo. 21 Q. I'm talking about subjects 22 expressed by this. 23 A. The example I just gave, I 24 don't believe is in here, although I would have Page 200 1 to read it again. There is some reference to 2 agitated and retarded depression, and that does 3 fit into these, not from the agitation side, but 4 this melancholic depression. I think there's 5 reference to severe depression. I would have to 6 go back and look for the words, but that struck 7 me as I read it that there was some of that 8 potential miscommunication. 9 Q. I want to get clear, Doctor 10 Wernicke, because this is something, frankly, 11 that's relatively new to us. We've not seen an 12 analysis of concomitant medications that 13 reflected that the concomitant medications given 14 to individuals in the Prozac group was equal to 15 that of individuals in placebo or comparator 16 drugs, and I really need your help to give me as 17 much information about what this analysis was, 18 who made it, when it was made, who else might 19 have been involved. Did you write the analysis 20 up? 21 A. As I remember, I did. 22 Q. It was something authored by 23 you? 24 A. Well, I took the data and put Page 201 1 the words around it, as I remember. 2 Q. All right. And the conclusion 3 of this was that concomitant medication was given 4 equally to all treatment groups? 5 A. As I remember there was no 6 statistical difference, it was numerically -- it 7 wasn't ten, ten, ten, I mean the numbers weren't 8 exactly identical, but there was no statistical 9 difference between the groups. 10 Q. Well, did you have to make a 11 statistical application in order to get this 12 equality or was it evident by virtue of just 13 looking at the numbers alone? 14 A. We always did that. It's not 15 something we sort of tried to put on if it didn't 16 look in the right trend, even if it came out 17 absolutely the way, if you want to put it that 18 way, one wanted to, we still would have applied 19 the statistical analysis, that was just part of 20 the package. 21 Q. Did anybody help you? 22 A. The statistician did, and I 23 know the next question is who is the 24 statistician. I believe at that time it was Page 202 1 Bruce Dornseif. 2 Q. Did you retain that document 3 in your files? 4 A. No. 5 Q. What did you do, throw it 6 away? 7 A. We submitted -- sent it all to 8 wherever we were preparing it for, and it was -- 9 Q. You didn't keep a copy? 10 A. I would have for a while, but 11 at some point I obviously threw it away. Not the 12 whole submission, these things were large, 13 voluminous, and they were archived somewhere, so 14 I didn't keep a copy of everything I participated 15 in. 16 Q. And you think it was either 17 submitted to the BGA or the FDA, but more than 18 likely it was the BGA? 19 A. Or it might have been the CSM. 20 A lot of these things were going on parallel, and 21 it might have been in several submissions, and I 22 honestly just don't remember exactly what 23 document this discussion went into at what time. 24 Q. Do you remember working with Page 203 1 any Lilly scientists, other than Doctor Dornseif, 2 in preparing this information? 3 A. No, I don't remember anybody 4 else closely involved. 5 Q. If Prozac is an activating 6 drug, would it be more likely to have a side 7 effect profile of suicide and suicide attempts, 8 Doctor Wernicke? 9 A. I don't know of any scientific 10 evidence to support that contention. 11 Q. You just don't know? 12 A. I don't believe so, I have no 13 reason to believe that. 14 Q. Do you have any reason to 15 dispute it, have you ever seen any study that 16 showed activating medications do not create 17 suicidality? 18 A. What I know is of a general 19 experience. Drugs like caffeine are activating, 20 and I've never heard anybody claiming that coffee 21 drinkers are more likely to commit suicide. 22 Q. Is that what you think is 23 occurring in these lawsuits, Doctor Wernicke? 24 A. I really have not been privy Page 204 1 to the details of these lawsuits, and what I know 2 is what I've heard on the media. 3 Q. All right. I'm not using the 4 term stimulating, I'm using the term activating 5 as is used by the Lilly employees in 6 characterizing the BGA's concerns, which has been 7 characterized as urgent and serious concerns by 8 the BGA at the time, correct? 9 A. It appears that way, yes. 10 Q. All right. Now, do you know 11 of any studies that have indicated that drugs 12 with activating properties do not have side 13 effect profiles of suicide and suicide attempts? 14 A. I know of no such studies that 15 address that issue. 16 Q. One way or the other? 17 A. One way or the other. 18 Q. So you don't dispute that an 19 activating drug might have a side effect profile 20 of suicide and suicide attempts? 21 MR. LORE: I object, that's not what 22 he's saying. 23 Q. You just don't know? 24 A. I just don't know, I -- Page 205 1 Q. Okay. Apparently somebody at 2 the BGA thinks there's some relationship, 3 correct? 4 A. Again, I've explained before -- 5 you're asking me to one, look into the mind of 6 the writer of this memo, and to take another step 7 further into the mind of the BGA. 8 Q. How about if we got you 9 something that was authored by the BGA in this 10 connection? 11 A. Then I would be able to 12 address that. 13 Q. Okay. Why don't we do that 14 after we take a break. 15 (A SHORT RECESS WAS TAKEN.) 16 Q. Back to Exhibit 3, Doctor. 17 Before we go to actually the BGA list of concerns 18 and the intent to reject letter of the BGA, let's 19 continue through what Doctors Weber and Schenk 20 have characterized earlier as the BGA's concerns. 21 Item twelve there says, the BGA stated that due 22 to the accumulation of fluoxetine, we should 23 consider to recommend a lower maintenance dose 24 after having achieved a certain relief of acute Page 206 1 symptoms. They advised to give clear 2 instructions concerning dose adjustments with 3 time, correct? 4 A. Yes. 5 Q. All right. Is it correct, 6 Doctor Wernicke, that there is, in humans, what's 7 known as an accumulation of fluoxetine with 8 respect to the fact that the fluoxetine 9 metabolites and fluoxetine itself have a long 10 half life? 11 A. Yes. 12 Q. Which means that, in lay 13 terms, it takes a while for Prozac to clear from 14 your system, is that right? 15 A. Yes. 16 Q. And what the BGA, at least, 17 stated to the Lilly employees in Germany that was 18 being related to Lilly employees in Indianapolis 19 was that there was a consideration of having the 20 symptoms relieved with some dosage, and then 21 after those depressive symptoms were relieved, 22 there be a lower maintenance dose, is that 23 correct? 24 A. I would interpret what they Page 207 1 said as that having been the case, yes. 2 Q. All right. Was there ever any 3 studies done that you're aware of while you were 4 a medical monitor of the U.S. clinical trials, in 5 which there were studies that measured giving 6 fluoxetine for a period of time until depressive 7 symptoms were relieved and then reducing the 8 dosage to see if there could be a maintenance of 9 the relief of depressive symptoms? 10 A. I was not aware of any such 11 studies. 12 Q. Do you know if there was any 13 consideration given to doing such studies? 14 A. I don't remember there being 15 such a discussion. 16 Q. Do you remember whether or not 17 Lilly ever addressed these concerns stated in 18 point twelve? 19 A. Yes, we did address that. 20 Q. In what way? 21 A. What we did is examine 22 patients under long-term therapy, and we looked 23 at a number of things, basically safety-related 24 things, and fairly sophisticated eye Page 208 1 examinations. And this has to do -- 2 Q. What examinations? 3 A. Eye, of the eyes. And let me 4 explain why we did this and how that also answers 5 this question. And that's alluded to elsewhere 6 in here at the top of this page. They talk about 7 phospholipidosis, which is something that's seen 8 in animals, which is basically an accumulation of 9 lipids, and since it was known that fluoxetine 10 and its active metabolites have a long half life, 11 the concern and question was does 12 phospholipidosis occur in humans. And I believe 13 it was the British authorities that brought up 14 that question, although here it was also 15 mentioned, but they, I believe, wanted us to look 16 at it in some detail. So to address that, we had 17 a number of examinations done, opthalmologic 18 examinations, chest x-rays, places where you 19 would see phospholipidosis, blood samples, white 20 blood cells we had examined by people in San 21 Diego that were world authorities on 22 phospholipidosis. 23 But more pertinent to this 24 question, we also looked at the blood levels that Page 209 1 were found in these patients on long-term therapy 2 and they were very similar to blood levels of 3 relatively short terms, say six weeks of therapy, 4 so there was certainly no escalation in the blood 5 levels. And we also found there was no good 6 relationship between blood levels and efficacy. 7 So putting all that together, we felt that yes, 8 we know that the drug accumulates, it doesn't 9 appear to have any toxic consequences, and since 10 we didn't know whether we would lose efficacy and 11 thereby put patients at a risk of relapse, we 12 felt firm in our conviction that we should go 13 with that dose and stay with that dose of twenty 14 milligrams a day. 15 Q. So you rejected the idea of a 16 recommendation that once individuals found relief 17 from the depressive symptoms, that the physician 18 consider lowering the daily dosage of fluoxetine 19 below the twenty milligram level? 20 A. The only way we could have 21 made that recommendation is with a study to 22 address that, we could not have just recommended 23 that. So it wasn't a matter of rejecting the 24 idea, it was a matter of us feeling that the dose Page 210 1 we had was a good starting maintenance dose. 2 Q. So you didn't do a study? 3 A. We did not do a study where we 4 lowered the dose to see if efficacy would be 5 maintained. 6 Q. Item fourteen we've touched on 7 briefly, but let's touch on it in a little more 8 detail. It says as we've already explained by 9 our telex to Doctor Zerbe of June 8, 1984 -- 10 which we've been discussing here as Exhibit 1 -- 11 continuing with the quote, we need a careful 12 analysis of suicides and suicide attempts, 13 patient by patient, symptomatology, severity upon 14 entry into the study, and week by week until the 15 event occurred, dose of fluoxetine, side effects, 16 et cetera. This is a very serious issue in the 17 opinion of the BGA. It might well be that we 18 will have to recommend concomitant tranquilizer 19 intake for the first two to three weeks in the 20 package literature, end quote, correct? 21 A. Yes. 22 Q. Doctor Wernicke, did you ever, 23 at any time, have any discussions with any 24 individuals at the BGA or any individuals on Page 211 1 Commission A concerning what is characterized 2 here as this very serious issue of suicide? 3 A. No, I did not. 4 Q. Was there ever any study done 5 where patients were systematically in a clinical 6 trial given concomitant tranquilizer intake for 7 the first two or three weeks of therapy? 8 A. Not systematically, not that I 9 was involved in or aware of. 10 Q. Do you know whether it was 11 ever considered to be done? 12 A. I don't remember it ever being 13 considered as a study in itself. 14 Q. So there's no scientific 15 evidence that was done by Lilly that would 16 indicate whether or not concomitant tranquilizer 17 intake for the first two or three weeks of 18 patients receiving fluoxetine would reduce 19 suicidality? 20 A. I'm not sure that -- I'm not 21 sure -- could you rephrase it or just repeat the 22 question? 23 Q. Sure. 24 (THE COURT REPORTER READ BACK THE Page 212 1 REQUESTED TESTIMONY.) 2 A. I'm not aware of any data to 3 speak to that. 4 Q. All right. 5 (PLAINTIFFS' EXHIBIT NO. 4 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Doctor Wernicke, I'm going to 9 hand you what's been marked as Exhibit 4, and ask 10 you to review that. 11 MR. SMITH: And Counsel, if it's all 12 right with you, I have been advised by our 13 videographer that we're at the end of the tape, 14 could we change the tape while he's reviewing 15 that document? 16 MR. LORE: Certainly. 17 (A SHORT RECESS WAS TAKEN.) 18 Q. (BY MR. SMITH) Doctor 19 Wernicke, have you had an opportunity to review 20 Exhibit 4? 21 A. Yes. 22 Q. Exhibit 4 appears to be a 23 four-page document. The first page is apparently 24 a transmittal letter, is it not? Page 213 1 A. Yes, it seems to be a summary. 2 Q. It says yesterday we 3 unofficially received a copy of the medical 4 comments on our fluoxetine application, a 5 translation is attached, correct? 6 A. Yes, that's the cover. 7 Q. And it's signed by B. Von 8 Keitz? 9 A. Barbara Von Keitz. 10 Q. All right. And you say she's 11 not a physician? 12 A. No, she was the regulatory 13 person in our Bad Homburg affiliate. 14 Q. She was the regulatory person, 15 is that right? 16 A. That's my understanding, yes. 17 Q. And attached are four pages, 18 are there not? 19 A. Yes. 20 Q. It's also dated May 25, 1984, 21 correct? 22 A. Yes. 23 Q. And it's entitled comment on 24 the clinical documentation, correct? Page 214 1 A. Yes. 2 Q. And this appears to be a 3 document that was authored by the BGA, is that 4 right? 5 A. This is a translation of such 6 a document apparently, yes. 7 Q. And does it appear -- did you 8 ever see the original document in German? 9 A. No. 10 Q. Do you think this is a 11 reliable translation done by your people in 12 Germany? 13 A. It appears to be. It's -- 14 some of it is somewhat awkward, so I would want 15 to see them side by side, I suppose, but I don't 16 see any major areas where I would see a lot of 17 confusion. 18 Q. All right. And this is 19 something that was translated by Lilly employees, 20 apparently? 21 A. Apparently. 22 Q. All right. And the BGA 23 apparently is taking a look at the clinical 24 documentation from a medical standpoint, is that Page 215 1 right? 2 A. It appears that way, yes. 3 Q. And what this document is is 4 reflective of their analysis of the data that has 5 been submitted by Eli Lilly and Company to them 6 in support of registration of Prozac for 7 marketing in Germany, is that correct? 8 A. If this is a true translation 9 of what was sent back from the BGA, I would 10 conclude that, yes. 11 Q. And again, you don't have any 12 reason to doubt that this is not a true 13 translation, do you? 14 A. No. 15 Q. The bottom paragraph of the 16 first page says of the forty-six attached study 17 protocols, in twenty-five the note is to be found 18 that these studies were not completed, correct? 19 A. It says that, yes. 20 Q. It continues to say each 21 double-blind study is preceded by a one-week 22 placebo wash-out period as statements on the 23 medications which were used in the pretreatment 24 of the depression are missing. The question Page 216 1 occurs, if firstly this period was not too short, 2 and on the other hand if a carry-over effect of 3 these drugs has not influenced the result of the 4 first examination before the beginning of the 5 studies, end quote, correct? 6 A. Yes. 7 Q. And again, this is the 8 comments made by the physicians at the BGA who 9 were responsible for overseeing whether or not 10 this product would be approved in Germany for 11 consumption by -- or for prescription by German 12 physicians to German citizens, is that right? 13 A. It appears that way, yes. 14 Q. Now, obviously by reading this 15 last sentence, or this last paragraph on the 16 bottom of page one and the first of page two, it 17 would appear that whatever documentation you 18 might have sent concerning concomitant 19 medications must have been sent after this was 20 authored? 21 A. I don't see that -- I don't 22 see that that follows. 23 Q. Well, because it says as 24 statements on the medications which were used in Page 217 1 the pretreatment of the depression are missing, 2 the question occurs if firstly this period was 3 not too short, and on the other hand, if a 4 carry-over effect of these drugs has not affected 5 the results of the study. 6 A. Well, they're talking about a 7 different time period, they're talking about the 8 lead-in phase to the study, and if before that 9 there had been other antidepressants -- before we 10 were talking about the concomitant use of drugs, 11 that's a totally different -- 12 Q. Okay. So their issue here is -- 13 their concern here was wait a minute, we don't 14 know what drugs these people might have been on 15 before they entered the clinical trials, and what 16 drugs they were on and what dosage they were on, 17 right? 18 A. Before. 19 Q. Before. 20 A. Before, right, this speaks to 21 before. 22 Q. And what we were talking about 23 is what drugs patients got in the clinical trials 24 while they were participating in the clinical Page 218 1 trials. 2 A. Yes. 3 Q. And the concern reflected by 4 this paragraph is we need this information to get 5 a more accurate picture of what's occurring in 6 the clinical trial process by knowing what 7 happened just before. 8 A. Yes, they wanted to know 9 whether there could be a carry-over effect. For 10 instance, if a patient had just come off another 11 antidepressant the day before they started this 12 one-week lead in, they thought there might be a 13 carry-over effect, if that in fact were the case. 14 Q. Does that seem like a 15 reasonable inquiry on their part? 16 A. Yes, certainly. 17 Q. And was that addressed at a 18 later date, do you know? 19 A. I don't remember whether that 20 was addressed. 21 Q. But from a scientific 22 standpoint, that would be a legitimate scientific 23 question to address. 24 A. Yes. I think it would be one Page 219 1 to address, but if -- I suspect from what we 2 know, that the outcome of such analysis would be 3 known because if there were in effect a 4 carry-over effect, you should see that before, in 5 fact efficacy got better over time. If there was 6 initial good efficacy that deteriorated, it would 7 lend more credence to the idea that maybe you 8 were seeing the result of something else. So 9 yes, it's a legitimate question, but we already 10 kind of knew the answer. 11 Q. But it was a legitimate 12 question on their part. 13 A. Yes. 14 Q. Did they appear to be acting 15 in the interest of German citizens in raising 16 that kind of question? 17 A. In the sense of evaluating the 18 efficacy of the compound, yes. 19 Q. All right. That would be more 20 of an efficacy question as opposed to a safety 21 question, is that right? 22 A. Yes. 23 Q. And the issue of concomitant 24 medications that were given during a trial might Page 220 1 affect both efficacy and safety, mightn't it? 2 A. Yes. 3 Q. All right. Turn to page three 4 with me of the exhibit. Actually it's got three 5 on the top of the page and four on the bottom of 6 the page. 7 A. Okay. Same page. 8 Q. The first paragraph states -- 9 and this, again, is the opinion of the medical 10 people at the BGA, is it not? 11 A. I'm not sure whether there 12 were physicians at the BGA that evaluated this, I 13 can't say that. 14 Q. Well, it says is the medical 15 comment. 16 A. Right, of the medical 17 evaluation. 18 Q. At least in the United States 19 when you say here's a medical comment, you think 20 it's coming from a physician, don't you? 21 A. You would think that. 22 Q. All right. So it's reasonable 23 for us to assume that there were some physicians 24 involved in this examination, would it not? Page 221 1 A. I think so. 2 Q. The top of that page, the 3 first paragraph says, and I quote, the frequency 4 of side effects was very high, partly more than 5 ninety percent, and the side effects resulted -- 6 and the side effects resulted nearly in each 7 study in dropouts. The frequency of sides 8 effects depended upon the dose, the age, and the 9 duration of therapy. And I cannot read that next 10 word, can you, sir? 11 A. It says deciding for the 12 clinical significance of side effect. That's why 13 I say the translation is a bit awkward and our 14 English was not all that good, and I think that's 15 part of the problem. 16 Q. Is continues to say, deciding 17 for the clinical significance of side effects is 18 not only the frequency of their occurrence, but 19 also their severity, end quote, correct? 20 A. Yes. 21 Q. So the criticism there is that 22 there were high side effects. 23 A. It appears to be, yes. 24 Q. And in some instances ninety Page 222 1 percent of the individuals were reporting side 2 effects, is that right? 3 A. Yes. 4 Q. And the side effects resulted 5 in dropouts from the studies, is that right? 6 A. Yes -- well, not all of them, 7 but there were dropouts due to side effects. 8 Q. Right. And it says also that 9 the frequency of the side effects depended on 10 dosage, correct? 11 A. Yes. 12 Q. Age of the patient. 13 A. Yes. 14 Q. And duration of therapy, 15 correct? 16 A. Yes. 17 Q. And this was significant -- 18 the significance of these side effects was not 19 only their frequency, but their severity, is that 20 correct? 21 A. That's what it says here. 22 Q. That tells me in English, in 23 Texas, and what I speak most, that these side 24 effects are occurring a lot and they're severe Page 223 1 side effects, is that correct? 2 A. I would read that as that is 3 what they suggested, that was their conclusion 4 from what this says. 5 Q. Continuing down on that page 6 of the medical comments made by the German 7 regulatory equivalent of the United States Food 8 and Drug Administration, four paragraphs down, it 9 says in fifteen to twenty percent of cases, side 10 effects occur which involve the central nervous 11 system. As most of them resemble the clinical 12 picture of the underlying disease, even from 13 theoretical reasons, one has to expect 14 intensification and not an improvement of 15 symptoms, end quote, correct? 16 A. Yes, that's what it says. 17 Q. It appears to me a little bit 18 awkward, the translation there, does it not? 19 A. That's why I qualified my 20 comment with the translation. 21 Q. Did you think or did you ever 22 talk to Ms. Von Keitz or anybody at Germany 23 concerning the meaning of this paragraph? 24 A. Well, not this paragraph, per Page 224 1 se, because I don't remember seeing this memo, 2 but we did discuss this issue of the symptoms of 3 depression that was similar to potential side 4 effects of the drugs. 5 Q. Then you decide that what they 6 were saying here or what their criticism here 7 was, that there were fifteen to twenty percent of 8 the side effects that were CNS side effects, 9 correct? 10 A. Yes. 11 Q. And that these side effects 12 were greater than the CNS side effects, were 13 greater than you would normally see in 14 individuals suffering from depression. 15 A. Well, they don't make any 16 reference here to anything else. What they're 17 saying is that some of the side effects are 18 symptoms, also could be symptoms of depression, 19 and that when they say on a theoretical basis, 20 that you would expect perhaps some of those 21 symptoms to increase in frequency, like insomnia. 22 Q. But what they're saying is 23 they're increasing with more frequency than you 24 would expect if they're part of the disease. Page 225 1 A. In addition to the disease, 2 yes, I interpret this as meaning that they think 3 that there would be some additional reports. 4 Q. All right. The next paragraph 5 says during the treatment with the preparation, 6 sixteen suicide attempts were made, two of these 7 were with success. As patients with the risk of 8 suicide were excluded from the studies, it is 9 probable that this high proportion can be 10 attributed to an action of the preparation, in 11 the essence that of a deterioration of the 12 clinical condition which reached its lowest 13 point, end quote, correct? 14 A. That's what it says. 15 Q. Is it true that patients with 16 risk of suicide were excluded from these studies 17 that they mentioned here? 18 A. One of the exclusion criteria 19 was patients with presumed high risk of suicide 20 potential. 21 Q. Wasn't the actual term, Doctor 22 Wernicke, serious risk? 23 A. That's what I said, serious. 24 Q. You said high risk potential. Page 226 1 A. Well, serious, high, I don't 2 remember the exact words, but the concept was 3 patients that were truly thought to be at a 4 fairly high risk should be excluded from the 5 study, and I don't remember the exact language. 6 Q. What was your understanding of 7 what a high risk of suicide was that would cause 8 an individual to be excluded from the clinical 9 trials? 10 A. If -- my understanding of that 11 was if in the clinical judgment of the 12 investigator, the treating psychiatrist, this 13 patient would be fairly likely to have -- make a 14 suicide attempt. Now that there's no other way 15 to quantify or qualify that, it's a clinical 16 judgment on the part of the investigator. 17 Q. Well, I think we've got some 18 more -- we're having some documents copied that I 19 think will give us a little better definition 20 there where you in fact yourself were addressed 21 this question and gave some response closer in 22 time to when this was occurring than -- I want to 23 be fair with you and let you see that, so we'll 24 pass that for this instance. But my question is, Page 227 1 when you came on board, did you understand that 2 these studies that had been submitted to the BGA 3 where they found the sixteen suicide attempts, 4 two of which were true suicides, in those studies 5 patients with serious suicidal risk were 6 excluded? 7 A. Yes, I remember that, yes. 8 Q. And it was the medical opinion 9 of the BGA at that time, in May, 1984, that 10 because these individuals with serious suicide 11 risk were excluded, that it was more probable 12 that the high proportion of suicides in the 13 fluoxetine group was attributable to the action 14 of Prozac versus the normal depressive 15 symptomatology, is that correct? 16 A. It's correct that that appears 17 to be their conclusion. 18 Q. All right. If you'll turn 19 with me to the next page that is marked page four 20 on the top, it says summarizing opinion, and then 21 under point two it says, quote, considering the 22 benefit and the risk, we think that this 23 preparation totally unsuitable for the treatment 24 of depression, end quote, correct? Page 228 1 A. Yes, it says that. 2 Q. Did you ever ask or make any 3 inquiry of the BGA what benefits they saw in 4 Prozac in May of 1984 -- 5 A. No. 6 Q. -- in writing this medical 7 conclusion? 8 A. No, I did not communicate with 9 them directly. 10 Q. Did you ever communicate with 11 the BGA concerning what risks they identified in 12 connection with the use of Prozac to come to the 13 conclusion that Prozac was totally unsuitable for 14 the treatment of depression? 15 A. No, I did not. 16 Q. This, of course, is a month 17 before you came with Lilly that this opinion was 18 delivered, correct? 19 A. Yes. 20 Q. And apparently had been 21 transmitted to Indianapolis on approximately the 22 same day, is that right? 23 A. Yes. 24 Q. And preceded by a month, this Page 229 1 June fourteen-point list of concerns that was 2 discussed as Exhibit 3, is that right? 3 A. Yes. 4 Q. The cover sheet of Exhibit 4 5 indicates that in Indianapolis, Mr. D. Thompson 6 was transmitted a copy of this document. Do you 7 see that? 8 A. Yes. 9 Q. Did you ever discuss this 10 document or did Mr. D. Thompson ever make you 11 aware of the contents of this document, Doctor 12 Wernicke? 13 A. Not this document in 14 particular. We talked about some of these 15 issues, but not this paper. 16 Q. This document also indicates 17 that it was sent to Doctor L. Thompson in 18 Indianapolis, does it not? 19 A. Yes. 20 Q. That's Doctor Leigh Thompson, 21 correct? 22 A. Yes. 23 Q. Did Doctor Leigh Thompson ever 24 give you this document or ask you -- or have any Page 230 1 discussions with you concerning any comments made 2 in this document? 3 A. I don't remember ever actually 4 seeing this document. I certainly have 5 conversations with a number of people about the 6 content, and I don't remember specific 7 conversations with Leigh Thompson specifically 8 about these kinds of this. I know we talked 9 about some of these issues. 10 Q. Did you know, generally, at 11 the time you came on, you know after you got 12 brought up to speed at Lilly, that the medical 13 aspect of the BGA in Germany considered Prozac as 14 being totally unsuitable for the treatment of 15 depression? 16 A. Yes, I knew of that 17 conclusion. 18 Q. Did you know that the medical 19 scientists at the BGA in Germany felt that it was 20 probable that the high proportion of suicides in 21 the clinical trials was attributable to the 22 action of Prozac? 23 A. I knew there was the opinion 24 at the BGA or in Germany, but I wasn't really Page 231 1 sure who and where it came from, that there were 2 a high number of suicides and that somehow that 3 was related to the mechanism of action, which is 4 why we did that analysis looking at the 5 denominator and the exposure. 6 Q. I guess that's why I was 7 asking you. Did you know it was a medical 8 opinion until you today have seen this as being 9 the medical comment from the BGA? 10 A. Well, when I heard that it was 11 a BGA concern, I mean I knew it wasn't from 12 toxicology, I knew it wasn't from manufacturing, 13 so I didn't further segment it to say medical, to 14 me that was all sort of one. It's like the FDA 15 making an inquiry, I don't say oh, gee, this is 16 the medical people, it must be more important. 17 It was important, we considered it. 18 Q. You certainly didn't consider 19 these items as being nit-picky, did you? 20 A. No. 21 Q. You certainly didn't consider 22 these as being merely technical regulatory 23 matters, did you? 24 A. No. Page 232 1 Q. Did Doctor Leigh Thompson give 2 you any directions in connection with what to do 3 about this situation in Germany? 4 A. Not specifically about this. 5 Q. Did he generally? 6 A. When we talked about the scope 7 of the job when I came on, he gave me general 8 instructions as to what to do. 9 Q. When you came on to talk to 10 Doctor Thompson about the scope of the job, did 11 he tell you that Prozac was in regulatory -- 12 medical regulatory problems in Germany? 13 A. I don't remember him saying 14 anything about that. 15 Q. What did he tell you about the 16 status of Prozac and its approval or nonapproval 17 in foreign countries at the time? 18 A. When we had these discussions 19 it was during the interview process, so I did not 20 anticipate, and certainly from what I know now, I 21 would not anticipate him to tell me about the 22 individual regulatory status. He told me about 23 the drug in general, what their plans were, what 24 he thought it did and why he thought it was Page 233 1 useful, but not about individual regulatory 2 status, it was rather confidential within the 3 company. 4 Q. I understand that. You knew 5 that Prozac had not yet been approved by the 6 United States Food and Drug Administration. 7 A. That's correct. 8 Q. And was still being considered 9 by the United States Food and Drug 10 Administration. 11 A. Yes. 12 Q. Do you know, Doctor Wernicke, 13 whether this medical comment on fluoxetine issued 14 by the BGA medical branch in May of 1984 was ever 15 transmitted to the United States Food and Drug 16 Administration? 17 A. I don't know that. 18 Q. All right. Did you ever send 19 Exhibit 4 to the Food and Drug Administration? 20 A. I don't remember ever seeing 21 this document before today. 22 Q. All right. What happened 23 specifically in connection with the approval 24 process of Prozac in Germany? Page 234 1 A. We received a list of their 2 concerns and questions and we prepared a response 3 which dealt with many of these issues. 4 Q. Was this list of concerns and 5 questions the same as is reflected by Exhibit 13 -- 6 I mean Exhibit 3? 7 A. Virtually, as far as I 8 remember. We had a list of questions, and I'm 9 not -- I can't say now without laying them side 10 by side whether they were all exactly the same, 11 but basically I think we tried to address all of 12 the concerns. 13 (PLAINTIFFS' EXHIBIT NO. 5 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 Q. Exhibit 5 is a document dated 17 January 29, 1985 authored by our friends Weber, 18 Chandler and Mayr in Germany, is it not? 19 A. Yes. 20 Q. You are copied with this 21 document? 22 A. Yes. 23 Q. Do you recall receiving this 24 document? Page 235 1 A. No, I don't, not specifically. 2 Q. It -- the subject of the 3 document is fluoxetine registrations in Germany, 4 is it not? 5 A. Yes. 6 Q. It says we unofficially 7 received -- 8 A. Our confirmation. 9 Q. -- our confirmation that 10 fluoxetine was discussed by Commission A at the 11 BGA on January 21st. Two major concerns seemed 12 to be the reason that the registration was not 13 accepted, correct? 14 A. Yes. 15 Q. Do you recall knowing in 16 January, 1985 that Prozac was not accepted by the 17 BGA? 18 A. Now in retrospect I don't 19 remember when I became aware of that, but 20 obviously I did. I was working on some of these 21 issue already by then, so I would have known 22 that. 23 Q. It says the two major reasons 24 that registration was not accepted was that there Page 236 1 was efficacy questions, correct? 2 A. Yes. 3 Q. And suicidal risk, correct? 4 A. Yes. 5 Q. So nothing had been done by 6 Lilly between May, 1984, when the medical comment 7 came in, and January, 1985, when Commission A 8 failed to accept the registration of Prozac, to 9 change the BGA's concern about efficacy and 10 suicidal risk? 11 A. Not in terms of a submission 12 to the BGA. You can't make a submission until 13 you get a response. The initial submission was 14 made, then you have to get something back to 15 respond to. So when you say nothing was done, 16 that was true from the BGA's perspective, but I 17 don't remember when we did the various analyses 18 in looking at the data because that was back 19 further. We knew this these were their concerns, 20 but we hadn't got an official letter. 21 Q. What do you consider Exhibit 22 4, where this is a scathing comment from the 23 medical section of the BGA that concludes that 24 considering the benefit of the risk, we think Page 237 1 that Prozac is totally unsuitable for the 2 treatment of depression, and it points out 3 numbers of suicide and that it is probable that 4 these suicides are the result of Prozac? 5 A. As I remember, that was not an 6 official communication, that was knowledge 7 transmitted. But when you deal with a regulatory 8 agency, you can only respond to official 9 communications. Just because somebody tells you 10 something, you can't say well, let's quick submit 11 something else, it doesn't work that way, 12 certainly not with the FDA. And from what I 13 understood, that was also true of the BGA. You 14 know what their concerns were and you could be 15 working on it, but you couldn't just call them up 16 or send them something. It's a very formal 17 process. 18 Q. We're going to talk about it, 19 we'll see how formal it really was. I'm going to 20 give you some documents where you all were 21 talking directly with the opinion leaders on 22 Commission A, okay? 23 A. When you say we, not me in 24 Indianapolis. Page 238 1 Q. Your people in Lilly in 2 Germany were, did you know that? 3 A. I'm not aware of who talked to 4 whom. 5 Q. Okay. Well, but again, is it 6 your testimony, Doctor Wernicke, that there 7 wasn't anything done in connection with this 8 suicide issue raised by the medical comment back 9 in May, 1984? 10 A. No, that is not my testimony. 11 As I told you a moment ago, we started to work on 12 that from -- 13 Q. What did you do between May, 14 '84 and January, '85? 15 A. I don't remember the dates 16 when we actually did this, but we evaluated the 17 suicide attempts and the gestures and compiled 18 all that. 19 Q. But that's later, Doctor 20 Wernicke. 21 A. That's why I say I don't 22 remember what we did at what time. 23 Q. What do you remember doing 24 between May, 1984, when you got this scathing Page 239 1 report -- don't you agree it's scathing? 2 A. Actually, when I look at it in 3 the totality and understanding why they came to a 4 lot of those conclusions, it's not nearly as 5 scathing as it would appear, to be honest with 6 you. 7 Q. You don't consider it 8 scathing, the summary that says that it is -- 9 considering the benefit and the risk, we think 10 this preparation is totally unsuitable for the 11 treatment of depression, that doesn't concern you 12 as being scathing? 13 A. You see, you have to remember 14 that what I learned is that -- there are two 15 elements to an approval of a drug, it's called a 16 risk/benefit ratio, that's inherent in every 17 therapy. They concluded that there was no 18 efficacy, which we knew was incorrect. But we 19 also knew what -- 20 Q. Let me stop you there. Why 21 couldn't the BGA see this? 22 A. I'm about to tell you that. 23 Q. You had your submission to the 24 United States Food and Drug Administration, the Page 240 1 NDA was submitted in September, 1983, and the 2 testimony is clear, and I think you'll agree, 3 won't you, that the submission of the NDA means 4 that Lilly, in submitting this to the FDA, 5 considers that everything has been done in 6 support of efficacy and safety of a product. Do 7 you agree with that proposition? 8 A. Not everything, there's always 9 more being done. Lilly considered and the FDA 10 agreed that what we submitted was approvable. 11 Q. All right. 12 A. And I also understand, and I 13 will be glad to explain this if you give me a 14 chance, why the BGA came to a different 15 conclusion. Would you like to hear that 16 explanation or is that not pertinent? 17 MR. LORE: Probably not, Doctor. Mr. 18 Smith is asking the questions. 19 MS. ZETTLER: I object to the side 20 comment. I also object to the nonresponsive 21 answer of the witness. 22 Q. (BY MR. SMITH) Did you talk 23 to any member of the BGA or Commission A on why 24 they rejected or filed an intent to reject the Page 241 1 application of fluoxetine hydrochloride in 2 Germany? 3 A. No, I did not. 4 Q. So then what you're fixing to 5 tell me, let's be clear, on why the BGA didn't 6 approve Prozac is going to be based on your 7 supposition and your assumption, is that right? 8 A. Yes. 9 Q. Okay. Will you also agree 10 with me that the BGA specifically wrote a letter 11 advising why they intended to reject Prozac? 12 A. I'm not sure whether they 13 wrote a letter or whether this was notes of a 14 meeting. That I'm just not -- 15 Q. They did vote. 16 A. Well, maybe they did. 17 Q. I'm fixing to give that to 18 you, by the way. I have it here and will give it 19 to you in just a minute, but we're not there in 20 chronological order yet. But if you want to stop 21 here and tell me now why you suppose that the BGA 22 did not approve Prozac back in January, 1985, 23 I'll certainly let you tell me. 24 A. I can tell you from the Page 242 1 efficacy standpoint why they were not convinced. 2 Q. Efficacy? 3 A. Efficacy. That's half of the 4 equation. The way studies are reported to the 5 FDA are as separate studies. The bulk -- one of 6 our pivotal studies was a multi-center study, 7 this is what you'll see referred to as a 8 fluoxetine, placebo, imipramine study. When you 9 look at each one of those investigation sites, 10 which were the small subset, and they allude to 11 this, a lot of them did show separate efficacy. 12 That's why it's more than a supposition on my 13 part why they came to that conclusion, because if 14 you do that they don't show efficacy. But it was 15 designed to be a multi-center study, and in fact 16 part of what we did was to show the pooling, 17 perhaps that should have been done before, and 18 for the FDA you always presented a separate 19 study. So I think the real problem came in is 20 that the submission was written for the FDA in a 21 format that they wanted to see it, and that's 22 somewhat different than the format that the BGA 23 sees them, and they looked at the same material 24 that the FDA concluded showed efficacy and Page 243 1 concluded that it didn't. Now it's the same data 2 and it's just a matter of how you present and 3 pool the data. In fact they asked us to go back 4 and pool the data and we did that and they said 5 oh, yes, I see now. And that's how a lot of this -- 6 Q. Wait a minute. You said they 7 said oh, yes, I see now. When you said oh, yes, 8 I see now, did you talk with them? 9 A. No. 10 Q. Who talked to them and they 11 said oh, yes, we see it now? 12 A. They accepted the submission 13 and they approved the drug. 14 Q. Now, that's not what you said, 15 you said oh, yes, I see now. Now is that not 16 true or did somebody talk to the BGA from Lilly? 17 A. When I said oh, yes, I see 18 now, I take -- meant that they approved the drug 19 so we must have demonstrated efficacy, not that I 20 talked to them or that somebody told me that I 21 talked to the BGA and they said oh, yes, I see 22 now. 23 Q. Why would you say, oh, yes, we 24 see now, like all of a sudden -- Page 244 1 MR. LORE: He's already told you, they 2 approved the drug, they must have found it to be 3 efficacious. 4 MR. SMITH: That's not what he said. 5 A. Yes, I did say that. 6 MR. LORE: That's exactly what he 7 said, Paul. You're trying to put some meaning on 8 what he said. 9 MR. SMITH: What I want to get clear 10 here is whether or not he's quoting something 11 somebody from the BGA said. 12 A. No, I'm not. 13 Q. I think that's very important, 14 don't you, Doctor Wernicke? 15 A. Actually, I don't think it's 16 very important. 17 Q. Whether or not you're talking 18 directly to the BGA? 19 A. I have told you multiple times 20 and I'll tell you again, I did not at any time 21 talk to any individual from the BGA or the 22 Commission A. 23 Q. That's why I was so concerned, 24 Doctor Wernicke, when you say they said oh, yes, Page 245 1 I see now. 2 A. Well, let me ask you this -- 3 maybe you should ask the questions, but do you 4 think somebody from the German BGA would call me 5 up and say yes, I see now? That was a figure of 6 speech to suggest that they had accepted the 7 efficacy, that's all it was. 8 Q. Okay, I understand you now. 9 Now -- but you said efficacy was only half the 10 equation, didn't you? 11 A. Yes. 12 Q. All right. Talk to me about 13 safety and why all of a sudden they reversed 14 their opinion on safety. 15 A. No, I don't -- again, I don't 16 know what's in their minds, but a lot of these 17 questions, like sixteen suicides on fluoxetine, 18 as I explained before was taken without 19 consideration of the exposure. They said there 20 were sixteen suicides and two deaths, explain 21 that, that was totally out of context. And as 22 far as I can tell, when we worked through all of 23 that and looked at the rates in fluoxetine and 24 the comparator and got the expert opinions, those Page 246 1 matters were addressed, as were the 2 phospholipidosis and a number of other issues. 3 Q. When you're talking about 4 rates of exposure, are you talking about patient 5 years? 6 A. That's one way to look at it, 7 number of patients, patient years. There were a 8 number of ways that one has to look at that type 9 of data, there's no one correct way, but one has 10 to -- 11 Q. Would you say it's incorrect 12 to just look at raw numbers? 13 A. It certainly doesn't lead to 14 any correct conclusion. 15 Q. Is it more appropriate to use 16 patient years than just raw numbers? 17 A. It's certainly more 18 appropriate than raw numbers, yes. It's like 19 saying there are a hundred auto accidents in 20 Houston and two in some other little town. 21 Without talking about the population, what does 22 that mean? That's the kind of comparison that 23 we're talking about. 24 Q. You see, one reason I have Page 247 1 trouble with that, Doctor Wernicke, is because I 2 thought that thu data that had been submitted by 3 Lilly to the BGA for approval was comparative 4 data, and it was data that compared numbers of 5 patients on Prozac, numbers of patients on 6 comparator drug and numbers of patients on 7 placebo, didn't it? 8 A. It appears that that's wrong. 9 If that was there, they didn't understand that 10 because that's not -- when we explained that, 11 that question was answered. So either it wasn't 12 submitted or they didn't understand it or they 13 missed -- I don't know why they came to that 14 conclusion, but when we looked at where those 15 numbers came from, it was clear right away that 16 these were the raw numbers in the fluoxetine 17 group, and other, no consideration of exposure, 18 number of patients, patient years. 19 Q. Okay. Then they were talking 20 about other safety concerns also in addition to 21 suicide, weren't they? 22 A. I believe there are mention of 23 other questions. 24 Q. They were talking about Page 248 1 activation and agitation, weren't they? 2 A. Yes. 3 Q. Were there some inaccurate 4 numbers or some numbers that were improperly 5 analyzed or submitted to them in a confusing way 6 that would cause them to come to this belief -- 7 A. Not that I know of. 8 Q. -- that you're aware of? 9 A. Not that I'm aware of. 10 Q. In any event, the issue of 11 suicidal risk in Germany continued eight months 12 later, in January, 1985, did it not? 13 A. It appears that way, yes. 14 Q. Now, we had a pretty serious 15 discussion about discussing things with the BGA 16 and members and officials of the BGA, did we not? 17 A. I believe so. 18 Q. Look with me at the bottom of 19 page four. 20 A. Now are we talking about 21 Exhibit 5? 22 Q. I'm sorry, look with me at the 23 first page of Exhibit 5, where it says in the 24 meantime the following action plans have been Page 249 1 initiated on fluoxetine. Do you see that? 2 A. Yes. 3 Q. One is meetings with clinical 4 experts to discuss possible ramifications, right? 5 A. Yes. 6 Q. The next is immediate follow 7 up on all key opinion leaders on the BGA 8 commission for selected visitation next week. 9 A. Yes, I see that. 10 Q. All right. So it looks like 11 there was going to be some direct one on one 12 selected visitation with German officials, 13 doesn't it? 14 A. This memo would imply that, 15 yes. 16 Q. Did you ever participate in 17 any of those actions? 18 A. No. 19 Q. Go on to the last paragraph 20 there. It says it's our intention to review all 21 appropriate communication channels prior to the 22 official response by the BGA. All pertinent 23 information will be communicated to keep everyone 24 informed on this important issue, correct? Page 250 1 A. Yes. 2 (PLAINTIFFS' EXHIBIT NO. 6 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.). 5 Q. Exhibit 6 is a document dated 6 February 27, 1985 and is directed to Doctor 7 A. J. Weinstein, is it not? 8 A. Yes. 9 Q. And it's signed for Doctor 10 Hans Weber by an individual in Germany, is it 11 not? 12 A. Yes, I believe so. 13 Q. Do you recognize that 14 signature, sir? 15 A. No. 16 Q. All right. The letter itself 17 is, in fact, a transmittal letter of the official 18 German BGA response, is it not? 19 A. It refers to that. 20 Q. Beg your pardon? 21 A. It refers -- yes, it's a cover 22 letter for what should follow a submitting 23 letter. 24 Q. All right. And it says the Page 251 1 letter, that is the BGA letter, is indeed an 2 intention of rejection and not a rejection itself 3 and we have three months in which to respond, is 4 that correct? 5 A. Yes, it says that. 6 Q. Did that -- I take it by that 7 that if there's not some response within three 8 months, that the product will be officially 9 rejected? 10 A. Yes. 11 Q. But if there's a response 12 within three months, that the product will be 13 again considered, is that right? 14 A. That's the implication. 15 Q. All right. And the second 16 paragraph says this was -- or the first paragraph 17 says this letter is mainly consistent with 18 objections which we've heard before, right? 19 A. Yes. 20 Q. In other words, this was 21 nothing new? 22 A. Yes. 23 Q. Then the second paragraph 24 states, compared with the first letter of Page 252 1 concerns, the insufficiently established 2 therapeutic efficacy and the unacceptable 3 damaging effects are again the main points. In 4 details, the reasons of the BGA are explained 5 more deeply, and there's some additional reasons. 6 And it goes on to state those additional reasons, 7 does it not? 8 A. Yes. 9 Q. Then it goes on, the next 10 paragraph says, the letter from the BGA is nearly 11 identical with the opinions of Professors 12 Herrmann, whom Doctor H. J. Weber and S. Heymanns 13 has visited a day before. According to his 14 opinion, the following problems exist: One, no 15 German (European) studies; two, studies with 16 monotherapy are lacking; three, a sufficient 17 number of inpatient studies are lacking. His 18 suggestion is two times a hundred and twenty 19 patients. And four, suicides, because a 20 suspicion is sufficient for refusal (his comment: 21 Duphar could show that there were the same or 22 even more attempted suicides in the controlled 23 group) period, end paragraph, correct? 24 A. Yes. Page 253 1 Q. So suicides was also raised in 2 the BGA intent to reject letter. 3 A. Yes, it would appear that way 4 from this memo. 5 Q. All right. Now who is 6 Professor Herrmann? It says this letter from -- 7 the letter from the BGA nearly identical with the 8 opinions of Professor Herrmann, whom Doctor Weber 9 and Heymanns visited the day before. 10 A. He is a German psychiatrist, 11 that's all I know. 12 Q. All right. Had you talked 13 with Professor Herrmann before this? 14 A. No, I've never talked to him. 15 Q. That was going to be my next 16 question. Have you talked to him since this? 17 A. No. 18 Q. Do you know of anybody that 19 has spoken with Professor Herrmann? 20 A. According to this memo, Hans 21 Weber did, and S. Heymanns. 22 Q. Who is S. Heymanns? 23 A. I'm trying to place him 24 exactly. As I remember, he was somewhere in the Page 254 1 management structure, the general manager, I 2 believe, but I never really had much interaction 3 with him, so I don't really know for sure. 4 Q. Of Lilly Prozac -- I mean of 5 Lilly in Germany? 6 A. I believe so. I'm not quite 7 certain. 8 Q. Did Doctor Weinstein share 9 this letter with you? 10 A. I don't remember seeing this 11 letter. 12 Q. Have you ever seen this letter 13 prior to today? 14 A. No. 15 Q. The last paragraph of this 16 transmittal said, I would like to get your 17 comment and specific direction to which points 18 are necessary to follow up for clarification. To 19 get a better understanding, we will begin 20 contacting during the next few days -- next days, 21 Strater, the BGA, paren, your questions, close 22 paren, and other opinion leaders prior to an 23 Indianapolis meeting. Your list of priorities 24 would assist our efforts for next week's Page 255 1 activities, correct? 2 A. Yes. 3 Q. Now who is Strater? 4 A. I don't know, I have never 5 heard that name. 6 Q. Up until today you've never 7 heard the name Strater? 8 A. It's not at all familiar. 9 Q. You've never seen the0name 10 Strater? 11 A. Not that I can recollect. 12 Q. On page one, do you see some 13 writing there up in the upper right-hand corner? 14 A. Yes. 15 Q. Do you recognize that writing? 16 A. No. 17 Q. There's mention in the 18 document, or this letter, a meeting in 19 Indianapolis shortly after this, is that correct? 20 A. Yes. 21 Q. Did you attend that meeting? 22 A. No. 23 Q. Did you ever see any notes to 24 that meeting? Page 256 1 A. No. 2 Q. Did you ever talk to anybody 3 that had been at that meeting? 4 A. No, I don't know anything 5 about that meeting. 6 Q. Do you have anything -- any 7 idea what was done in that meeting? 8 A. No. 9 Q. Do you know why you wouldn't 10 know or be invited to that meeting, Doctor 11 Wernicke? 12 A. Well, this memo was written to 13 Doctor Weinstein, this was a fairly high-level 14 meeting of what appears to be upper management. 15 That would be the only reason that I could think 16 of. 17 Q. Well, by January, 1985, or 18 February, 1985, you were fairly familiar with the 19 United States clinical trials in connection with 20 Prozac, weren't you? 21 A. Yes. 22 Q. In fact you were responsible 23 for the United States clinical trials on Prozac, 24 weren't you? Page 257 1 A. Yes. 2 Q. Had you, by February, 1985, 3 examined or done any analysis of these issues in 4 connection with the concerns of the BGA? 5 A. I don't remember the exact 6 dates when I did what, but I was heavily involved 7 in the whole process. 8 Q. Were you involved in the whole 9 process before the original intent to reject 10 letter was sent? 11 A. I believe so. 12 Q. All right. So do you have any 13 explanation why your expertise and your work in 14 connection with this issue was not brought to 15 bear with a meeting -- where you would be 16 involved in a meeting on this issue? 17 A. Well, the implications of the 18 meeting agenda are that this is to plot the 19 regulatory strategy for Germany, not to deal with 20 the data and the substance of the questions. 21 This was apparently from, what I read in here, to 22 figure out who is going to do what and how to 23 proceed from there, more on a logistic -- from a 24 logistic standpoint. Page 258 1 Q. Okay. Are you saying at that 2 time they were generals and you were a soldier? 3 A. I think that would be fair to 4 say. 5 Q. All right. 6 A. Maybe a sergeant, but not a 7 general. 8 Q. I didn't say you were a 9 private. 10 (PLAINTIFFS' EXHIBIT NO. 7 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Exhibit 7 is the official 14 intent to refuse registration of Prozac issued by 15 the German BGA regulatory body, is it not? 16 A. Yes. 17 Q. It's signed by an official 18 that calls themself a doctor, Doctor U. Schmidt, 19 correct? 20 A. Yes. 21 Q. Do you know whether Doctor 22 U. Schmidt is a medical doctor? 23 A. I do not know. 24 Q. Do you know that in Germany Page 259 1 it's customary that the head of the BGA be a 2 physician, such as is customary in the United 3 States that the head of the United States Food 4 and Drug Administration be a physician? 5 A. I was not aware of that. 6 Q. Does that surprise you? 7 A. No. 8 Q. Have you ever seen this 9 document before? 10 A. I don't remember seeing this 11 specifically. 12 Q. All right. Do you know if 13 this document has ever been submitted by Lilly to 14 the United States Food and Drug Administration 15 for their review? 16 Q. A. I do not know that it has. 17 Q. All right. The document on 18 page one says they intend to refuse the 19 registration. 20 A. Yes. 21 Q. And it sets forth the reasons 22 for their refusal, does it not? 23 A. Yes. 24 Q. Number one says the drugs are Page 260 1 not sufficiently tested according to the secured 2 state of scientific knowledge, and the 3 therapeutic efficacy, which is claimed for them, 4 is insufficiently substantiated, correct? 5 A. It says that, yes. 6 Q. It goes on to say in point 7 two, for the drugs concerned -- and they're 8 talking about Prozac, aren't they? 9 A. Yes, I think so. 10 Q. It says for the drugs 11 concerned there is, according to their specific 12 profile of adverse effects, the justified 13 suspicion that they have unacceptable damaging 14 effects, correct? 15 A. It says that. 16 Q. Point two point one states 17 that the German regulatory body in refusing this 18 for the reason that, quote, the use of the 19 preparation seems objectionable, as the increase 20 in agitating effect occurs earlier than the 21 mood-elevating effect and therefore an increased 22 risk of suicide exists, end quote, doesn't it? 23 A. It says that, yes. 24 Q. Point two point two on the Page 261 1 second page says, in addition, quote, during 2 treatment with the drugs some symptoms of the 3 underlying disease, paren, anxiety, insomnia, 4 agitation, close paren, increase, which as 5 adverse effects exceed those which are considered 6 acceptable by medical standards, end quote, 7 correct? 8 A. It says that, yes. 9 Q. Did you see this document 10 shortly after it was authored on February 27th? 11 A. I don't remember seeing this 12 specific document. 13 Q. Did you ever discuss 14 specifically the contents of this document in any 15 meeting in connection with your work of Prozac? 16 A. Yes. While I was involved in 17 addressing all of these issues, there were many 18 meetings in many contexts to try to address 19 these, as we've talked about before, the 20 submissions to the BGA. 21 Q. I understand that, but did you 22 ever sit down and take the official document and 23 defined the reasons for -- and spelled out the 24 reasons for the rejection? Page 262 1 A. I don't remember seeing this 2 exact document. 3 Q. Okay. 4 A. I may have, but almost ten 5 years ago, I don't remember. 6 (DISCUSSION OFF THE RECORD.) 7 (PLAINTIFFS' EXHIBIT NO. 8 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Exhibit 8 is a document 11 authored by Doctor Johanna Schenk who is a Lilly 12 physician in Germany, is she not? 13 A. She was at that time. 14 Q. And do you know where Doctor 15 Schenk is now? 16 A. No. Last I heard she took a 17 job with Shering Plough, I believe, but I don't 18 know where she is right now, that was years ago. 19 Q. Was she a native of Germany, 20 as far as you know? 21 A. Yes. 22 Q. And it's directed, we think, 23 to the individuals listed at the top of page one, 24 correct? Page 263 1 A. It would appear that way. 2 Q. There's some confusion in 3 connection with dates, because we see some dates 4 in early April, and the text of the first page 5 indicates that it's a report of a fluoxetine 6 working meeting that occurred on April 29th and 7 30th, correct? 8 A. Yes, there would appear to be 9 a discrepancy. 10 Q. You're listed as a recipient 11 of this document. 12 A. Yes. 13 Q. Do you recall receiving this 14 document, Doctor Wernicke? 15 A. Not specifically, no. 16 Q. Do you recall generally 17 receiving something of this nature? 18 A. Yes. 19 Q. Specifically do you recall 20 that there was a report or a note from Doctor 21 Schenk summarizing a report of Doctor Herrmann, 22 who was an expert called in to help Lilly in 23 Germany in registering Prozac as Fluctin in 24 Germany? Page 264 1 A. I remember discussion about 2 the report Doctor Herrmann wrote, but I don't 3 remember any specific documents summarizing that. 4 Q. All right. What was the 5 discussion about the report Doctor Herrmann 6 wrote? 7 A. That basically he summarized 8 what his views were of what was in the 9 submission, why the BGA had not accepted, what we 10 should do to meet their needs and concerns. 11 Q. All right. And what did you 12 do in connection with this report, anything? 13 A. One of the items that I 14 remember being -- becoming more and more 15 apparent, that was what was really one of the 16 issues, is that the BGA felt that there should be 17 studies in Germany. 18 Q. All right. 19 A. So one of the things we did 20 was start bringing those into reality, protocols, 21 and getting those going. 22 Q. All right. Now the suicide 23 issue has been raised by the medical comments at 24 the BGA, right? Page 265 1 A. Yes. 2 Q. The suicide issue was also a 3 part of the official reason that Germany issued 4 their intent to reject Prozac in Germany, 5 correct? 6 A. Yes. 7 Q. Then on page two of this 8 document, Professor Herrmann, in this summary of 9 his opinion, indicates concern about suicide, 10 correct? 11 A. Yes, it appears that way. 12 Q. Specifically Professor 13 Herrmann apparently points to the fact that 14 suicide attempts have been observed more 15 frequently on fluoxetine as compared to 16 imipramine. It says only epidemiological data or 17 literature or other antidepressants may help to 18 identify whether it happened by chance that 19 incidents of suicide attempts were abnormally 20 high on fluoxetine or abnormally low on 21 imipramine, correct? 22 A. Under comparators, it says, 23 yes. 24 Q. Right. And above that it Page 266 1 mentions specifically imipramine as the 2 comparator, does it not? 3 A. Yes. 4 Q. And on the first page, it says 5 that Doctor Herrmann has reviewed the original 6 documented -- original documentation submitted 7 March 1st, 1984, and the analysis of pooled 8 studies, fluoxetine versus imipramine versus 9 placebo, protocol number twenty-seven, submitted 10 October, '84, correct? 11 A. Yes. 12 Q. So it appears that Doctor 13 Herrmann has focused in specifically on this 14 pooled analysis comparing Prozac, imipramine and 15 placebo. 16 A. It appears that way, yes. 17 Q. And he notes an abnormally 18 high incidence of suicides on Prozac versus 19 imipramine. 20 A. Higher on Prozac than 21 imipramine. 22 Q. All right. 23 A. Not whether each of them was 24 abnormal, just relative. Page 267 1 Q. He found it was higher -- 2 A. Yes. 3 Q. -- in the Prozac treated group 4 than the imipramine treated group. 5 A. That appears to be what it 6 says here, yes. 7 Q. All right. Do you know what 8 data he's referring to? 9 A. I know the study. 10 Q. All right. 11 A. It's -- well, protocol 12 twenty-seven, it was a three-arm comparison of 13 fluoxetine to imipramine to placebo. 14 Q. Is it correct, as is stated in 15 the medical comment -- I forgot what exhibit it 16 is there -- that there were sixteen suicide 17 attempts, two of which were completed in the 18 fluoxetine group, and none in the imipramine 19 group? 20 A. No, that's not correct. They 21 didn't address the comparators at all, and that 22 was from the entire data base, including 23 compassionate use. What they're talking about is 24 not just this study, this is a subset of that. Page 268 1 Q. How many suicides or attempted 2 suicides were there in protocol number 3 twenty-seven? 4 A. I don't remember. 5 Q. Then how do you know they're 6 not looking at protocol twenty-seven? 7 A. Because I know that some of 8 those, of the sixteen, were from 9 compassionate-use studies. I know that they were 10 not in protocol twenty-seven. I don't know how 11 many came from protocol twenty-seven, per se. 12 Q. All right. But -- okay, so 13 Doctor Herrmann even points specifically to 14 something different as a cause of concern for 15 suicide attempts, that is specifically protocol 16 number twenty-seven, and the medical comment 17 issued by the BGA points to sixteen in general as 18 a cause for concern. 19 A. And these are a subset of 20 those sixteen. 21 Q. Right. 22 A. They're not different, they're 23 a subset of that. 24 Q. Compassionate use was included Page 269 1 in protocol number twenty-seven in the data. 2 A. But not in their comparative 3 phase. The way the study works is there's a 4 controlled phase which was -- 5 Q. I know how the study works. 6 A. But then the compassionate-use 7 phase, or the extension, does not carry forth the 8 comparator groups, not placebo. Patients could 9 elect to stay on imipramine, and I don't know how 10 many did, but it's not as if these three groups 11 are carried along, most patients then go on to 12 fluoxetine. 13 Q. All right. But each of them 14 is seeing two different sets of numbers and 15 raising concerns about those. 16 A. Not two different sets, one is 17 a subset of the other. 18 Q. All right. Well, they're 19 looking at the numbers in two different ways and 20 seeing a concern. 21 A. Or making an observation, yes. 22 Q. All right. Well, they're both 23 making that observation as a concern, in truth, 24 aren't they, Doctor Wernicke? Page 270 1 A. It would imply that in the way 2 this is written, yes. 3 Q. Did you ever see Doctor 4 Herrmann's twenty-one page report as is mentioned 5 here in this document? 6 A. I don't remember ever seeing 7 that, no, I think I would have remembered that. 8 Q. Either in German or in 9 English? 10 A. No. 11 Q. Did you ever talk with a 12 Professor Herrmann? 13 A. No. 14 Q. Do you know where Professor 15 Herrmann lives or lived? 16 A. No. 17 Q. Did you ever make any 18 inquiries as to the location of Doctor Herrmann? 19 A. No. I knew he was in Germany, 20 that's as far as I knew. 21 Q. Do you know anything about his 22 background? 23 A. No. 24 Q. Do you know why he was chosen Page 271 1 as a consultant by Lilly to help them in this 2 analysis of these various problems presented by 3 the BGA? 4 A. Not specifically, no. 5 Q. Do you know who would know 6 that? 7 A. Somebody in the German 8 affiliate that chose him, that worked with him. 9 Q. Do you think that would be 10 Professor -- or Doctor Weber, maybe? 11 A. Doctor Weber or Doctor Schenk. 12 Q. Did you ever discuss Doctor 13 Herrmann or his report with Doctor Leigh 14 Thompson? 15 A. I don't remember specifically 16 ever discussing that, per se. 17 Q. How about Doctor Bob Zerbe? 18 A. Not in relation to Doctor 19 Herrmann's report. We certainly talked about the 20 issues. 21 Q. How about Doctor Dan Masica? 22 A. The same is true there, we 23 didn't segment it out as Doctor Herrmann's 24 report, per se. Page 272 1 Q. Were there any psychiatrists 2 on board at Lilly in-house at that time, in -- 3 A. '85? 4 Q. -- April of '85? 5 A. I'm trying to remember when 6 Doctor Ivan Bennett left. He was a psychiatrist, 7 and he, sometime during my tenure there, retired, 8 but I don't remember whether he was there at this 9 particular time. 10 Q. Do you remember anything 11 Doctor Ivan Bennett did in connection with 12 Prozac? 13 A. No, I'm not sure he was 14 involved at all. 15 Q. He wasn't involved at all, in 16 fact, was he? 17 A. No, not to my knowledge. 18 Q. Do you know of any 19 psychiatrists in-house at Lilly who were working 20 on this concern? 21 A. At this time? 22 Q. Yes. 23 A. No, I'm not aware of any. 24 (PLAINTIFFS' EXHIBIT NO. 9 WAS Page 273 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 Q. Exhibit 9 is a telex with an 4 action plan graphic representation on the second 5 page that apparently is dated March 27, 1985 and 6 was authored by G. Mayr, T. A. Chandler and 7 Doctor J. Schenk, correct? 8 A. Yes. 9 Q. Who is G. Mayr? 10 A. He was the general manager in 11 either Europe -- all of Europe, I believe all of 12 Europe. I know he was at one point, at this 13 moment I'm not sure. He might have been for 14 Germany. When I met him once, he was the general 15 manager in Europe. 16 Q. Is he a physician? 17 A. No. 18 Q. How about T. A. Chandler? 19 A. I believe he was from the 20 marketing area, I don't really -- 21 Q. From where? 22 A. From the marketing business 23 development area. I'm not quite sure, I don't 24 remember ever meeting him. Page 274 1 Q. Is he a physician? 2 A. Not that I know of -- no, I 3 don't believe so. 4 Q. We've already identified 5 Doctor Schenk. 6 A. Yes. 7 Q. All right. All three of these 8 individuals are in Germany, correct? 9 A. I presume so -- I don't know 10 about Chandler. 11 Q. Or were in Germany at the 12 time. 13 A. Mayr, I'm not sure if he was 14 general manager of all of Europe, he may or may 15 not have been. I can't say with certainty that 16 they were all in Germany. 17 Q. Do you recall receiving this 18 memo? 19 A. Not specifically. 20 Q. You're an addressee -- 21 A. Yes. 22 Q. -- of the memo, and then your 23 name is mentioned in the body of the memo, is it 24 not? Page 275 1 A. Yes. 2 Q. And if you turn over to page 3 two, there's a list and a date line of some 4 things to be done, right? 5 A. Yes. 6 Q. The first thing on the list is 7 BGA contact, correct? 8 A. Yes. 9 Q. And it lists there that this 10 would be done in the first week in April. 11 A. Yes. 12 Q. That would be done by Doctor 13 Karkos? 14 A. I don't know if it's by Doctor 15 Karkos or whether Doctor Karkos is on the BGA, it 16 just has his name in parentheses and I don't know 17 who that is. 18 Q. All right. Or whether Doctor 19 Karkos is the BGA contact. 20 A. That's the question, I don't 21 know. 22 Q. So this indicates to me that 23 there was some contact with the BGA. 24 A. At least that's the plan as Page 276 1 represented here. Whether that actually 2 happened, I don't know. 3 Q. It's listed first on the plan, 4 isn't it? 5 A. Right, yes. 6 Q. Also there's going to be -- 7 the second thing that's mentioned is some 8 generation of new data out of Indy, isn't it? 9 A. Yes. 10 Q. And that's going to occur 11 between March 25th and April 21st, correct? 12 A. Yes. 13 Q. It doesn't say who's going to 14 do the generation of the new data, does it? 15 A. It doesn't say that, no. 16 Q. It doesn't identify what new 17 data is going to be generated either, does it? 18 A. Not here. 19 Q. What new data was generated? 20 A. I don't remember specifically. 21 I remember answering these questions and Doctor 22 Schenk coming over and us working together on 23 them. The data I remember was the pooling and 24 the looking at the efficacy and looking at the Page 277 1 parameters on the Hamilton scale, it wasn't -- it 2 was analysis of the data that was there, looking 3 at different subsets of it. 4 Q. That's my question, Doctor 5 Wernicke. What I want to know is what new data 6 was generated? 7 A. It was new analyses -- it says 8 new data, but there was no new data input, it was 9 a reanalysis or further analysis of what was 10 already done, as far as I remember. For instance 11 looking at the Hamilton individual questions and 12 subscales. 13 Q. Well, it doesn't say that, 14 though, does it? 15 A. No, but you asked me what I 16 remember about it. Because I remember being 17 involved in this item five, the drafting of the 18 reply. 19 Q. It doesn't say reanalysis of 20 existing data, does it? 21 A. It doesn't say that. 22 Q. It says generation of new 23 data. 24 A. That's what it says here. Page 278 1 Q. Now I want to be real clear 2 with you, Doctor Wernicke. Is it your testimony 3 here that there was no new data generated for the 4 British -- I mean for the German government? 5 A. Will you clarify exactly what 6 you mean by new data, because I can't quite 7 answer. I told you what I remember happening, 8 and I don't consider that as new data, but some 9 people -- it's certainly new analysis. So if 10 you'll define what you mean, then I can answer. 11 Q. I can't because all I can do 12 is read what's before me, that was written nine 13 and a half years ago by somebody across the 14 country, across the ocean, I guess. It says 15 generation of new data. 16 A. And my testimony is that, as I 17 remember what that means, and the only thing that 18 I remember being involved in is a further 19 analysis of the data that we had been analyzing. 20 Q. All right. But you don't know 21 of any new additional data that was generated out 22 of the computers there at Lilly in Indianapolis? 23 A. Again, let me clarify, new 24 analysis that may never have been done before, Page 279 1 numbers that may never have been seen. Now is 2 that new data in the sense that that is an 3 analysis that's not been done, that's new, is it 4 new in that more information was put in more 5 studies, and the answer is no. So data is kind 6 of an ill-defined word and you have to really be 7 very specific if you want a specific answer. 8 Q. I would if I could, but it's a 9 term used by a Lilly employee nine and a half 10 years ago, it's -- all I can do is use what term 11 they're using. 12 A. But I have a pretty specific 13 memory of the activities around that because I 14 remember Doctor Schenk coming over and all of us 15 working on these answers. 16 Q. Was this then data that was 17 massaged? 18 A. One massages people, not data. 19 There were new analyses that were done that had 20 not been done previously. 21 Q. My term massage is not my 22 term. 23 A. It's not mine either. 24 Q. All right. Page 280 1 A. And I don't use it in the 2 context of data. 3 Q. Do you think that it's 4 unscientific to use the term massaging and data 5 in the same context? 6 A. It's certainly not a word I 7 would use, and I don't really know what people 8 would mean if they said that. 9 Q. Would it give you a negative 10 connotation in connection with what was done with 11 that data if you heard the term massaging data? 12 A. I would have to look at it in 13 the context of who said it. If it was massaged 14 in the intent of learning more, I would not think 15 of it as negative. If it appeared to have an 16 intent of making things look different, then I 17 would think it would have a negative content. 18 Q. All right. You think that it 19 could be interpreted as, the word massaging data, 20 as meaning making data look different? 21 A. By some people, that could be 22 the case. 23 Q. All right. Now it's talking 24 about, in item three, interpretation of new data. Page 281 1 A. Yes. 2 Q. Reports J. Wernicke, 3 S. Bandak? 4 A. Yes. 5 Q. And that was to occur from 6 March 25th through April 21st, is that right? 7 A. Yes. 8 Q. All right. And your name is 9 there under interpreting the new data. What new 10 data did you interpret? 11 A. I was involved in the analysis 12 interpretation of the different cuts we did on 13 the efficacy, looking at the different subscales 14 on the Hamilton, looking at them over time. I 15 don't remember whether we had already dealt with 16 the suicide issues, rates, that may have been 17 done before, that may have been part of this, I 18 don't remember. But the the main thrust of this 19 was looking at the efficacy, pooling the studies 20 and doing the analysis of the time, issues like 21 that. 22 Q. Then it looks like the next 23 thing that was going to be done was to present 24 the data to experts, and then it says, paren, Page 282 1 J.S., close paren. 2 A. Yes. 3 Q. Would that be Doctor Schenk? 4 A. Yes. 5 Q. So it looks like that there 6 was going to be some new data generated, this new 7 data was going to be interpreted, and then it was 8 going to be presented to the expert. 9 A. Yes. 10 Q. Then there was going to be, 11 next, drafting of a reply, and that was going to 12 be done by Bandak, Wernicke and Schenk, is that 13 right? 14 A. Yes. 15 Q. And that was not going to be 16 done until April 22nd-28th. 17 A. Correct. 18 Q. Correct? 19 A. Yes. 20 Q. When you say drafting of 21 reply, what reply is being -- are they referring 22 to there? 23 A. The reply to the BGA. 24 Q. All right. Do you recall Page 283 1 working on the reply to the BGA? 2 A. Yes, that's what I was 3 referring to earlier. 4 Q. Was it completed by the 28th? 5 A. That, I don't remember. 6 Q. Was it completed approximately 7 the 28th? 8 A. I believe about that time. 9 I'm not quite sure whether there was a delay, 10 whether we actually met the schedule, that's just 11 too long ago. 12 Q. What was the size of that 13 document? 14 A. About eight inches. 15 Q. Eight inches? 16 A. Two big volumes. 17 Q. Two big volumes of eight 18 inches or -- 19 A. No, two big volumes of about 20 four inches each, or maybe three inches each, 21 something like that. 22 Q. Three to four inches each? 23 A. Right. 24 Q. Did that reply contain all Page 284 1 information that you felt necessary at the time 2 to alleviate the German government's concern 3 about Prozac and suicidality? 4 A. It contained all the 5 information we had and our interpretation of it, 6 and we were certainly hopeful that that would 7 answer their questions. 8 Q. Was there any new data 9 generated on the suicide issue? 10 A. Well, we updated what we had 11 in our DEN system, we certainly pulled that in. 12 When you say new data as compared to what they 13 had seen in the submission of '83, there would 14 have been new information, yes. We basically 15 updated with the new data we had. 16 Q. Okay. There should have been 17 higher numbers of suicides. 18 A. And higher numbers of patients 19 exposed, yes. 20 Q. Right. So we'll be clear, the 21 data upon which the BGA rejected the application 22 was the same data that had been submitted to the 23 FDA in the NDA in support of safety and efficacy 24 of the drug, is that right? Page 285 1 A. In general, but we don't know 2 whether they submitted everything that we 3 submitted to the FDA. 4 Q. How would we know what was 5 submitted to the BGA? 6 A. You would have to go to 7 Germany and look at their submission files, 8 that's the only way that I would -- 9 Q. At Lilly or at the BGA? 10 A. At Bad Homburg in Lilly, I 11 suppose. 12 Q. They shld have that? 13 A. Well, I would think so, we 14 always kept copies of our submissions. I don't 15 really know about the inner workings of all the 16 affiliates. 17 Q. Were there any reports of 18 suicide or suicide attempts that had been 19 previously reported of suicide and suicide 20 attempts that were deleted in the resubmission to 21 the BGA? 22 A. They weren't deleted. We 23 asked an expert to come in and -- an outside 24 expert, to review this data with us and to make a Page 286 1 case-by-case determination whether some of these 2 events, episodes, were actually suicide attempts, 3 because sometimes it's not quite clear, and they -- 4 when I say they, there were several people 5 involved, one full professor and several of his 6 associates, and they concluded that some of these 7 were not. Now I don't think we actually deleted 8 them, I think we discussed them in that context 9 and said we're not counting this as a suicide 10 because of these opinions. 11 Q. So you resubmitted additional 12 data that contained this analysis where you had 13 deleted some suicides that had been previously 14 reported as suicides or attempted suicides, and 15 reanalyzed the data based on deletion of 16 previously reported attempted suicides or 17 suicides? 18 A. That was in general the 19 process that we tried to clarify these episodes. 20 I think, as I remember, we discussed them all, 21 but gave the reason why they weren't considered 22 in their calculation. 23 Q. And you put in new tables -- 24 A. Yes. Page 287 1 Q. -- analyzing the new suicide 2 numbers where you had deleted previous numbers 3 that had been reported as suicides. 4 A. Yes. 5 Q. Or suicide attempts. 6 A. Yes, we had moved those into 7 another column or another part of the submission. 8 But they were all -- they weren't deleted 9 completely, they were just considered separately. 10 Q. Okay. 11 A. When you say deleted, that 12 sounds like they weren't there at all anymore, 13 that was not done with any case. 14 Q. But there were new tables 15 submitted where they weren't, weren't there, even 16 though there had been an explanation that these 17 new tables were created after some had been 18 deleted? I'm not saying necessarily anything was 19 misrepresented to the BGA, I'm just saying it was 20 represented in a different form and there were 21 some additional tables that were presented to the 22 BGA that contained numbers of suicides that 23 weren't present that had been previously listed 24 as numbers of suicides or attempted suicides. Page 288 1 A. See, I don't remember that 2 that's the way it was actually done or whether 3 they were on the same table but they were flags, 4 I just don't remember the details of how that 5 data was presented. It may have been all in the 6 same table, and those flagged, I just don't 7 remember how we did that. 8 Q. Okay. What part of the reply 9 did you participate in, Doctor, did you actually 10 author any part of the reply? 11 A. Yes. 12 Q. What parts did you author? 13 A. There were a number of 14 questions that I participated in. I think the 15 whole document had, I believe, twenty or so 16 sections, and I was involved in, to some extent, 17 probably half of those. Some of them I wrote 18 completely, I believe the one on the 19 phospholipidosis. I was certainly involved in 20 the suicide analysis, but I don't know whether -- 21 other people were involved in the writing of 22 that, too. It was quite a long time ago and we 23 all worked on it quite intensively, so I don't 24 remember exactly who all did what. Page 289 1 Q. Next item that's listed here 2 on this action plan is discuss reply with 3 Professor Herrmann, Stille, Strater, and then he 4 puts in paren, lawyer, close paren. Did you 5 discuss the reply with either Professors 6 Herrmann, Stille or Strater? 7 A. No. 8 Q. The next thing that's listed 9 is approval process Indy. Do you see that? 10 A. Yes. 11 Q. What does that mean? 12 A. We circulated major documents 13 for submission as a routine among management. We 14 did that with all submissions to regulatory 15 bodies. 16 Q. Oh, I see, the reply had to be 17 drafted and then that reply had to be approved 18 within the Lilly corporate structure. 19 A. Yes, correct. 20 Q. And it says write final reply, 21 rediscussion with consultants if major changes, 22 correct? 23 A. Yes. 24 Q. Who at Indianapolis was Page 290 1 responsible for final approval in this approval 2 process? 3 A. Allen Weinstein would have 4 been involved, either Robert Zerbe or Leigh 5 Thompson, or both. Those are the only two 6 individuals that definitely were involved in that 7 process. 8 (DISCUSSION OFF THE RECORD.) 9 Q. All right. Then, as I 10 understand it, in this approval process, the 11 official submission to the BGA had to be 12 submitted to these medical managers at 13 Indianapolis. 14 A. Or the substance of it. I 15 don't know that they had to see the final form of 16 the submission, they had to see the answers to 17 the questions and the substance of the 18 submission. 19 Q. Somebody at Lilly had to give 20 the final document, that was going to be sent to 21 Germany, approval. 22 A. That was done, compiled and 23 put together in Bad Homburg in Germany. 24 Q. Well, no, it says final Page 291 1 approval -- it says approval process Indy. 2 A. Yes. 3 Q. That's what I'm talking about. 4 A. Right, the substance of the 5 submission. 6 Q. Okay. So just a draft was 7 approved here in Indianapolis? 8 A. No -- excuse me. When I talk 9 about the substance, I mean the answers to the 10 questions. Now when that -- you just don't put 11 that in an envelope and send it to the 12 government, there's a cover letter that's 13 paginated the proper way, it may have page 14 numbers. I don't think they saw all those 15 mechanical things of the submission, they may or 16 may not, but that would have required sending it 17 back and forth. What they approved or would have 18 seen was the answers to the questions, but not a 19 final draft unless there was some changes 20 required. 21 Q. All right. The bottom half of 22 this action plan talks about experts in 23 connection with efficacy, suicidal risk and 24 phospholipidosis. Page 292 1 A. Phospholipidosis. 2 Q. Phospholipidosis. 3 A. Yes. 4 Q. Under suicidal risk, the 5 experts that are going to be contacted are 6 Pohlmeier and Winzenried. 7 A. Yes. 8 Q. Right? 9 A. Yes. 10 Q. Are those both German? 11 A. They're not American 12 psychiatrists. 13 Q. Okay. 14 A. I presume they're German, but 15 I don't know that for a fact. They could be 16 other European. 17 Q. Did you meet with either -- 18 A. No. 19 Q. -- Doctor Pohlmeier or 20 Winzenried? 21 A. No, I did not. 22 Q. Why? 23 A. I wasn't asked to. 24 Q. Well, weren't you responsible Page 293 1 for writing those portions of the BGA -- response 2 to the BGA in answering their concerns concerning 3 suicidality? 4 A. Yes, but my report would have 5 gone to them, too, for them to have an opinion 6 on. 7 Q. Your report would have gone to 8 them? 9 A. Well, they would have seen it 10 in order to help evaluate our response. 11 Q. Did you have any 12 communications in writing with Doctor Pohlmeier 13 or Winzenried? 14 A. No. 15 Q. Why? 16 A. I don't know, I just didn't. 17 Q. Do you know of anybody that 18 did? 19 A. I don't know if anybody 20 actually talked to them. This is a list of 21 people that they're listing as experts from the 22 German affiliate, but I don't know anybody who 23 actually talked to them and whether and how and 24 what they said. Page 294 1 (PLAINTIFFS' EXHIBIT NO. 10 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. You don't need to -- you can, 5 but you don't have to analyze every graph and 6 every word written there, just -- you're free to 7 do that if you like, Doctor, but maybe -- 8 A. Let me just flip through it so 9 I'm familiar with it. 10 Q. Just familiarize yourself with 11 it generally. 12 A. All right. 13 Q. This Exhibit 11 or 12 -- 14 A. Ten. 15 Q. -- 10, is a document 16 apparently authored by Doctor C.D. Hardison dated 17 April 10, 1985, is it not? 18 A. Yes. 19 Q. It's entitled "Summary of 20 Suicide Attempt Rates and Time Course of 21 Attempts," correct? 22 A. Yes. 23 Q. You are copied in on this 24 document. Page 295 1 A. Yes. 2 Q. This occurs in a time, I 3 believe, during this action plan where data was 4 being assembled, is that right? 5 A. Yes. 6 Q. Do you know if this data was 7 submitted to the BGA? 8 A. I know we submitted this as 9 part of our response to Bad Homburg to be used 10 for that. How and in what form it was finally 11 submitted, I don't know. 12 Q. Who is Doctor C.D. Hardison? 13 A. He was a statistician at that 14 time. 15 Q. All right. So he's a Ph.D 16 doctor? 17 A. Yes. 18 Q. As opposed to an M.D. doctor? 19 A. Yes. 20 Q. Or does he hold both -- 21 A. No. 22 Q. -- degrees? You have both 23 degrees, don't you? 24 A. Yes. Page 296 1 Q. What is your Ph.D in? 2 A. Biochemistry. 3 Q. All right. Turn with me to 4 page thirteen, table eleven. 5 A. Uh-huh. 6 Q. That table apparently is a 7 listing of suicide attempts by drug in Phase 2 8 and 3 clinical trials, studies of unipolar major 9 depressive disorder, correct? 10 A. Yes. 11 Q. And this includes, as I think 12 you stated earlier, there was some carry-over 13 compassionate use of Prozac in the clinical 14 trials, is that right? 15 A. Yes, that's why you see much 16 longer times of fluoxetine than the comparators, 17 that stops abruptly and then those patients go 18 into the fluoxetine group. 19 Q. It's reflected there. 20 A. Yes. 21 Q. And of course number of 22 patients on Prozac over the longer period of time 23 appears to diminish substantially, does it not? 24 A. Yes. Page 297 1 Q. If you look at the table under 2 fluoxetine, you'll see how many suicide attempts 3 up to week fifty-four. 4 A. I see eight. 5 Q. How many do you see after week 6 fifty-four? 7 A. Some of them are kind of 8 overwritten. Two -- there may be one hidden, I 9 see two. 10 Q. All right. Under imipramine, 11 a comparator drug, how many suicide attempts do 12 you see? 13 A. I can't identify any unless 14 there's some under this stamp-over. 15 Q. Do you see any, Doctor 16 Wernicke? 17 A. I don't see any, no. 18 Q. Under Doxepin, how many 19 suicide attempts do you see? 20 A. I don't see any here. 21 Q. Under Amitriptyline, how many 22 suicide attempts do you see? 23 A. I see one. 24 Q. Under placebo, people getting Page 298 1 no drug, how many suicide attempts do you see? 2 A. I don't see any. 3 Q. So would it be accurate to say 4 that up to week fifty-four, you had ten 5 individuals -- eight individuals who attempted 6 suicide on Prozac, none on imipramine, none on 7 Doxepin, one on Amitriptyline, and none on 8 placebo? 9 A. Well, the placebo only goes to 10 week six, so one can't talk about week 11 fifty-four, you either talk about week six all 12 across to the lowest number or you talk any data 13 where there's fifty-four. 14 Q. So if you compare Prozac for 15 the first six weeks, how many suicide attempts do 16 you see on the Prozac treated group? 17 A. Five. 18 Q. And how many do you see in the 19 first six weeks on the placebo group? 20 A. None. 21 Q. Five versus none, correct? 22 A. Correct. With -- at week six, 23 four hundred twenty-two patients on fluoxetine 24 and ninety-six on placebo. Page 299 1 Q. Did I ask you that, Doctor? 2 A. I'm sorry, I'm just trying to 3 understand the numbers here. 4 Q. All right. Look after week 5 fifty-four, would you? 6 A. Yes. 7 Q. The only patients, it really 8 appears, of any numbers that were taking Prozac -- 9 or taking drugs were Prozac patients, right? 10 A. Yes. 11 Q. How many suicide attempts do 12 you see there? 13 A. Two. 14 Q. Was this data submitted to the 15 BGA? 16 A. I don't know. 17 MR. SMITH: I think we're kind of at a 18 stopping point. It's fifteen to 6:00, do you 19 want to stop? 20 MR. LORE: That's fine. 21 (DEPOSITION ADJOURNED FOR THE DAY.) 22 (CONTINUATION OF EXAMINATION BY MR. 23 SMITH) 24 Q. Good morning, Doctor Wernicke. Page 300 1 A. Good morning. 2 Q. We're beginning your second 3 day of your video deposition, and this is the 4 first part of the second tapu of the second day. 5 We've waived the readministration of the oath, 6 but you understand that you're still under oath 7 and that you must tell the truth in this 8 proceeding? 9 A. Yes. 10 Q. Yesterday you told us about an 11 analysis that you made or that was made under 12 your direction in connection with concomitant 13 medications given to patients during the clinical 14 trials of Prozac, correct? 15 A. Yes. 16 Q. In that analysis, did you take 17 into consideration the dosage of the comparative 18 concomitant medications? 19 A. I don't remember whether we 20 did or not. 21 Q. In other words, was there any 22 distinction made between five milligrams of 23 Valium versus ten milligrams of Valium? 24 A. I don't -- I understand the Page 301 1 question, I don't remember doing something with 2 that. I don't know whether we did or did not, I 3 just don't remember. 4 Q. Would that be likely or 5 unlikely that you did that? 6 A. That's very difficult to say, 7 it depends on the outcome of the initial 8 analysis, how much we wanted to know. I just 9 can't say whether it would be likely taken out of 10 context. 11 Q. That would be a legitimate 12 inquiry, would it not? 13 A. Certainly. 14 Q. To know if the dosage was 15 increased or decreased during the period of the 16 clinical trials? 17 A. Yes, that would be a 18 legitimate inquiry. 19 Q. Did you make an analysis in 20 this review of concomitant medications given to 21 patients in the Prozac clinical trials as to the 22 duration of time for which these patients 23 received concomitant medications? 24 A. I don't remember doing that Page 302 1 either. I only remember that we analyzed the use 2 of concomitant medications, but beyond that, in 3 more detail, what all we did or didn't look at, I 4 just don't remember the details. 5 Q. How long a patient took a 6 concomitant sedative or sleeping medication would 7 be a legitimate inquiry in making a determination 8 with respect to whether or not the clinical trial 9 outcome was affected by the use of concomitant 10 medications, would it not? 11 A. Yes, I would agree. 12 Q. Did you take into account 13 whether or not patients receiving concomitant 14 medications during the wash-out period, the 15 placebo wash-out period, and were continued or 16 discontinued on concomitant medications following 17 the actual week that there was a comparison in 18 the clinical trials? 19 A. I would have to look at the 20 protocols again, but as I remember, patients 21 weren't allowed to take concomitant medications 22 in the lead-in period, but that's a little fuzzy 23 in my mind. 24 Q. Well, what if a patient had Page 303 1 been on chloral hydrate, a sleeping pill, when 2 they entered the trial, they would not be taken 3 off of the sleeping pill during the placebo 4 wash-out period, would they? 5 A. I don't know. What I'm trying 6 to remember is whether they would be allowed into 7 the trial in the first place, and it may be, I 8 would just have to look at the protocols, that 9 was too far back to remember those details. 10 Q. Well, would you take my word 11 since I have looked at the protocols? 12 A. I would not. 13 Q. You would not take my word? 14 A. I'm sorry, I would want to see 15 the protocol myself. 16 MS. ZETTLER: The problem, Doctor 17 Wernicke, is the protocol has not been produced 18 to us. 19 THE WITNESS: That's not my problem, 20 I'm sorry. 21 Q. Whether or not a patient was 22 taking a medication, a concomitant medication, 23 during the placebo wash-out period, and whether 24 or not the patient continued that medication Page 304 1 after the actual comparison part of the trial 2 began, would also be a legitimate inquiry, would 3 it not, sir? 4 A. Yes, it would. 5 Q. And you just don't know 6 whether or not your analysis included any of 7 those factors. 8 A. That's correct, I just don't 9 remember that level of detail about that 10 analysis. 11 Q. All the detail that you can 12 remember about that analysis is that the number 13 of individuals in the clinical trial receiving 14 concomitant medications was statistically 15 significantly equal among the groups. 16 A. It was no statistically 17 significant difference is the -- 18 Q. That's probably the better way -- 19 A. That's the scientifically 20 mathematically correct way to say it, but it 21 means the same thing, yes. 22 Q. Do you feel, Doctor Wernicke, 23 that it's appropriate to administer concomitant 24 psychotropic medications to individuals Page 305 1 participating in a clinical trial where there is -- 2 where the purpose of the clinical trial is to 3 measure the safety and efficacy and changes in 4 individual's mood and behavior? 5 A. It's appropriate, first of 6 all, if that is part of the protocol, but I think 7 more importantly their need and the medical 8 condition of the patient always has to supersede 9 everything else. One cannot jeopardize the 10 patient, and although in the purest sense it 11 would be nice to not have anybody on any other 12 medications, but in reality that's very hard to 13 implement, so one tries to design the protocol as 14 rigidly as possible, yet allowing for the 15 individual patient's condition that has to be 16 considered on a medical basis. 17 Q. All right. Well, maybe my 18 question wasn't phrased right. Obviously if a 19 patient has a legitimate medical need to be on a 20 concomitant medication, I can understand why, 21 from a medical standpoint, it would be 22 appropriate to continue that patient on the 23 concomitant medication. However, my question is, 24 in designing a clinical trial and in looking at Page 306 1 the analysis of a clinical trial where you're 2 measuring changes in moods and behavior by virtue 3 of the administration of a psychotropic 4 medication, from a scientific standpoint isn't it 5 a valid inquiry to know whether or not those 6 patients might be taking other psychotropic 7 medications during the clinical trial? 8 A. Yes, it's certainly a valid 9 inquiry. 10 Q. And it's potentially -- the 11 reason for that is that there is a potential that 12 you might not be getting a true measure of the 13 action of the psychotropic medication under 14 investigation, but in fact be getting a measure 15 of a combination of the two psychotropic 16 medications. 17 A. That's correct. 18 Q. Additionally, if there were 19 changes that occurred in individual's mood or 20 behavior during a clinical trial, if they were 21 receiving other medications that were affecting 22 individual's mood or behavior, it would also be 23 difficult to measure whether that change was the 24 result of the investigative drug causing that Page 307 1 change or whether it's the comparator -- the 2 concomitant medication that's causing the change, 3 correct? 4 A. Yes, I would agree with that, 5 yes. 6 Q. And if a patient were to 7 experience anxiety during a clinical trial while 8 not on a concomitant medication, and that patient 9 experienced -- and that patient was administered 10 a tranquilizing medication, such as a 11 benzodiazepine, and that anxiety decreased over 12 the period of the clinical trial, wouldn't it be 13 logical to question whether or not that decrease 14 in anxiety was the result of the patient's 15 underlying condition getting better or was the 16 result of the administration of the concomitant 17 tranquilizing medication? 18 A. That would be a very 19 legitimate question, yes. 20 Q. And it's your testimony that 21 those type of questions weren't addressed by you 22 in your analysis, that you know of, other than 23 simply making an inquiry as to the equality of 24 the amount of administration of concomitant Page 308 1 medications across treatment groups? 2 A. It's my testimony that all I 3 remember was considering the drugs, how many 4 patients took drugs, and I don't remember the 5 extent of the analysis that was done, because 6 this was almost ten years ago. 7 (PLAINTIFFS' EXHIBIT NO. 11 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.). 10 Q. Doctor Wernicke, we've handed 11 you Exhibit 11, and I'll tell you in advance I 12 don't intend to go with you line by line and page 13 by page with this document. You're certainly 14 free to read each and every word on the document, 15 but I'm going to speak to you primarily in 16 generalities. 17 A. Yes, that's fine, go ahead. 18 Q. But why don't you take a 19 minute to review the contents because it's 20 several different letters and groups of analyses. 21 A. All right. 22 Q. Exhibit 11 is a set of 23 documents, hopefully all on the same subject, is 24 that correct? Page 309 1 A. Yes. 2 Q. The first page of Exhibit 11 3 is a letter dated August 20, 1985 transmitting 4 the documents that are the rest of the exhibit, 5 is that right? 6 A. Yes. 7 Q. And it's signed by you and 8 dated August 20, 1985, as I said, correct? 9 A. Correct. 10 Q. And basically what these are 11 is -- the next several pages are communications 12 and analyses that you had made of the suicide and 13 suicide attempt data that had occurred during the 14 clinical trials, is that correct? 15 A. Yes. 16 Q. And was this done in response 17 to the inquiries and concerns made by the BGA? 18 A. Yes. 19 Q. And was this in preparation 20 for a response to the BGA? 21 A. It was done in conjunction 22 with that. I don't remember exactly which 23 response this was being done, nor when we would 24 have submitted it, but it was done to deal with Page 310 1 that issue and that question. 2 Q. Well, would this have been 3 something that if the German government was still 4 interested in suicide and suicide attempts which 5 had occurred during the Prozac clinical trials, 6 would this be something that you would feel 7 comfortable in submitting to your Lilly affiliate 8 in Germany for their presentation to the 9 regulatory scientists in Germany? 10 A. Yes. 11 Q. Now, what data is this that 12 these reports covered, is it the pooled data from 13 all clinical trials? 14 A. Well, there are a number of 15 comparisons, and as explained in some of the 16 memos, one has to look at it a number of ways. 17 If one wants to look at comparator data, it's the 18 comparator studies, but then there is also 19 information about all the entire sample. So it's 20 almost everything, everything that there was, but 21 looking at it in different ways. 22 Q. All right. And it was done by 23 Doctor Winokur at the University of Iowa, is that 24 right? Page 311 1 A. He consulted with us. We did 2 the analysis and sent it to him, then he and his 3 colleagues came down and met with us, that's when 4 we went over the individual cases, and they 5 decided from the material that was available 6 whether in fact these were suicide attempts or 7 gestures or not, and then they sent us these 8 letters summarizing their findings. 9 Q. All right. But in any event, 10 it was your intent to present to these 11 consultants -- can we call them consultants? 12 A. Yes. 13 Q. The body of the Prozac 14 clinical trial data in connection with suicide 15 and suicide attempts? 16 A. Yes. 17 Q. And you presented to them any 18 and all data that would have reflected suicides 19 and suicide attempts? 20 A. Or even the possibility of an 21 event that could, in some sense, be interpreted 22 as that. 23 Q. Right. How did you determine 24 that last phrase that you used, the possibility Page 312 1 that in some instances it could have been a 2 suicide attempt? 3 A. We searched the DEN data base 4 and the clinical trial data base for terms that 5 suggested an act of violence or some sort of 6 trauma. We looked at trauma, overdose, any term 7 that could -- we would then have to read the 8 description to try to determine whether there was 9 any flavor at all of any type of suicide 10 behavior. 11 Q. Was this data that had been 12 reported as adverse reactions that had occurred 13 during the clinical trials? 14 A. Some of it was, some came into 15 the DEN system. 16 Q. But it would get to the DEN 17 system as reported by the investigator as an 18 adverse event that occurred during the clinical 19 trials? 20 A. Not all adverse events go to 21 the DEN system. 22 Q. All right. But would all the 23 basics, the underlying start place from your data 24 have been from reports from the clinical Page 313 1 investigators, is my question. 2 A. That, plus any spontaneous 3 reports that might have come from Europe, 4 although at that time I don't remember that -- 5 Q. It wasn't marketed anywhere. 6 A. So it would have been somehow 7 or other from the clinical trials, yes. 8 Q. That's what I wanted -- I want 9 to define what this body of data is that these 10 gentlemen were looking at, okay? 11 A. Yes. If there were only 12 clinical trials, that would be, of course, all it 13 came from, and at this time that would be all 14 there was. 15 Q. And these would be -- have 16 been adverse events -- the source of this data 17 would have been receipt of adverse events from 18 the Lilly clinical investigators in the field? 19 A. Correct. 20 Q. And these were Lilly clinical 21 investigators that were psychiatrists -- 22 A. Yes. 23 Q. -- that Lilly had hired to 24 administer the clinical trials. Page 314 1 A. Had a contract with. They 2 weren't working for Lilly, the one gives a 3 contract to do the study. 4 Q. But the reason that Lilly 5 entered into a contract with these investigators 6 is because they had experience, training and a 7 reputation as individuals knowledgable in the 8 field, is that correct? 9 A. Yes. 10 Q. And those individuals would 11 administer the clinical trials, administer the 12 Hamilton Depression Scales and the other scales, 13 and report back to Lilly. 14 A. Yes. 15 Q. Those investigators were also 16 advised to report adverse reactions to their 17 drugs and report that back to Lilly -- to the 18 drug -- occurring in the patients, and report 19 those back to the corporate offices? 20 A. The only modified drugs, they 21 were instructed to record and report all adverse 22 events, regardless of presumed causality. The 23 way you said it, adverse reactions to the drug, 24 they were not allowed, and in fact specifically Page 315 1 instructed not to make a judgment. They could 2 write down if they thought -- and we asked them 3 to write down if they thought it was related, but 4 no matter what happened they were to report. 5 Q. Yes, they were to report it -- 6 theoretically, they were not even to know what 7 drug the patient was on, correct? 8 A. That's correct. 9 Q. Unless it was compassionate 10 use -- 11 A. Or an extension -- it could 12 have been an open extension at that time. 13 Q. Was that included, 14 compassionate use and open extension, in this 15 data? 16 A. Yes. 17 Q. All right. So the 18 investigators may have known that a particular 19 patient would be on fluoxetine in recording an 20 adverse event, but the point you're making is the 21 investigator was not supposed to draw any causal 22 connection between the event and the report. 23 A. They -- 24 Q. And the study drug, I'm sorry. Page 316 1 A. Right. On the 1639s, in the 2 DEN system, there is a space for them to indicate 3 whether or not they thought it was study drug 4 related, but they were specifically instructed to 5 report everything, not to filter them, not to 6 report only things that they thought might be 7 related, although they could indicate their 8 opinion. 9 Q. I understand that. But -- 10 well, was it -- do you recall whether or not the 11 protocols requested that the investigator, in 12 reporting an adverse event, make some judgment or 13 determination with respect to whether or not it 14 was related to the -- the event was related to 15 the study drug? 16 A. As I remember, in at least 17 some of the studies, the case report forms did 18 leave an option to indicate that. 19 Q. No, I'm talking about the 20 protocols that were the guidelines and 21 instructions to the clinical investigators 22 concerning making a determination of causation. 23 A. I don't remember that being in 24 any protocol. Page 317 1 Q. All right. 2 A. Although the case report form 3 is really an extension of the protocol, that's 4 the implementation, so the instructions on the 5 case report form, in a sense, are part of the 6 study process, although that may not be exactly 7 what's in the protocol. 8 Q. All right. So the point 9 you're making is that this data that is the basis 10 of these consultants' review, was data that was 11 submitted to the -- by the investigator as an 12 adverse event to Lilly without necessarily any 13 determination one way or the other as to 14 causality of event to the study drug, is that 15 correct? 16 A. Correct. 17 Q. But it was data that was 18 transmitted to Lilly by its investigators as an 19 adverse event. 20 A. All of these would have been 21 an adverse event, I can't think of a situation 22 where something would have been in here that 23 would not be an adverse event in some sense. 24 Q. And the investigator in the Page 318 1 field on the spot was to characterize that 2 adverse event, was he not? 3 A. Describe it, yes. 4 Q. Describe it. 5 A. Yes. 6 Q. Now, we've got Doctor Winokur, 7 who was, I assume, a psychiatrist that reviewed 8 this. 9 A. Yes, a professor of 10 psychiatry. 11 Q. All right. We have Doctor 12 Woolson, who was a biostatistician, is that 13 right? 14 A. Yes, as I remember, that's 15 correct. 16 Q. And Doctor Coryell, who is 17 also a medical doctor, psychiatrist. 18 A. Yes. 19 Q. And they all came to 20 Indianapolis and went over this data with you. 21 A. Yes. 22 Q. Did they take case report 23 forms and things of that nature back with them or 24 copies of it back with them for further analysis Page 319 1 in Iowa? 2 A. No, we had sent them that 3 material before and they brought it back to us, 4 so -- to give them a chance to review it. 5 Q. All right. And so they made 6 several analyses in several different ways, did 7 they not? 8 A. Well, Bruce Dornseif did the 9 actual analyses and sent them the material, and I 10 don't remember whether they actually did any on 11 their own. They may have, I don't know that, 12 whether they reentered the data and analyzed it 13 again. 14 Q. Well, I thought that's what 15 one of Doctor Woolson's functions was, to make a 16 statistical analysis of this data, Doctor 17 Wernicke? 18 A. His function was to be a 19 biostatistician, statistical consultant. If he 20 looked at what Doctor Dornseif did and agreed 21 with it, I'm not sure that he would have felt he 22 would have needed to redo that. I just don't 23 know whether he would have done that again, the 24 exact same thing that Doctor Dornseif did. Page 320 1 Q. Well, in your cover letter to 2 Doctor Leigh Thompson, you say the bottom line is 3 that there is no statistically significant 4 difference in the number of attempts observed, et 5 cetera, et cetera. 6 A. Yes. 7 Q. So it appears to me that you 8 were asking them to make a statistical analysis 9 independently of that done by Doctor Dornseif. 10 You could tell whether there was a statistical 11 significance based on Doctor Dornseif's opinion 12 without calling these guys in, couldn't you? 13 A. Yes, but we called them in to 14 look at the whole situation, not just to repeat 15 his analysis. 16 Q. But one of the things that you 17 asked him to do, my point is, is to make a 18 statistical analysis in addition to other things. 19 A. I don't remember asking them 20 to repeat the analysis. We asked them to look at 21 what we had done, to look at cases, to render an 22 opinion, and what they actually did in Iowa, I 23 can't say, they may or may not have, I don't 24 know. I don't remember him saying that yes, I Page 321 1 entered all this data, I analyzed it again. He 2 may have, I don't know. 3 Q. Okay. I'm going to help you. 4 You've got some documents there in front of you, 5 and if you look at the letter of July 22, 1985 6 from Doctor Dornseif -- 7 A. Yes. 8 Q. -- that's the letter that was 9 sent to these gentlemen, right? 10 A. Yes. 11 Q. And he says, in summary, we 12 are analyzing a pool group of Phase 2 and 3 13 clinical trials as though it was -- is a 14 traditional observational study for which such 15 variables as suicide attempts were not part of 16 the a priori considerations, but were observed, 17 in quotes, as part of the adverse event recording 18 mechanism. Hence a wide range of P values are 19 possible, depending on the analysis. Since we 20 have analyzed a variety of ad hoc groupings, we 21 came up with a variety -- a widely varying set of 22 P values. This should not be surprising, period, 23 end quote, correct? 24 A. Yes. Page 322 1 Q. Now this P value stuff and 2 things of that nature and this a priori stuff, 3 that's statistician language, isn't it? 4 A. Well, many of us find that 5 useful, and understand it. 6 Q. It's language that has to be 7 understood before it's useful, isn't it? 8 A. Yes, I would say so. 9 Q. And it's language that's best 10 understood by statisticians, isn't it? 11 A. Yes, I would say. 12 Q. Since it is statistical 13 meanings to their particular field of science, 14 correct? 15 A. Yes, that's correct. 16 Q. Then he has tables that are 17 included within his group, right? 18 A. Yes. 19 Q. Now in Doctor Winokur's 20 analysis of July 1, 1985, which apparently was 21 made twenty-one days before Doctor Dornseif's 22 letter to Doctor Woolson, the statistician, 23 right? 24 A. Yes, I believe those are Page 323 1 correct dates. 2 Q. Check them out. 3 A. Right, that's correct. 4 Q. What Doctor Winokur has done 5 is go back and reanalyze the attempted suicides 6 and suicides, correct? 7 A. Yes. 8 Q. And what he has done is he has 9 characterized as not suicides or as not suicide 10 attempts some of the suicides and suicide 11 attempts that had already been collected by 12 Lilly. 13 A. Well, he evaluated the cases 14 we had in this analysis that we, not being 15 psychiatrists, were considering. That's why we 16 asked him, since he actually was a widely 17 published author on the issue of suicide, we 18 specifically asked him to help us sort all of 19 this out, because we felt, one, that we were not 20 really experts in this area, and certainly being 21 within the company that we shouldn't reconsider 22 cases. And that's specifically why we asked him 23 to consult. 24 Q. You're not telling this jury, Page 324 1 are you, Doctor Wernicke, as the clinical 2 monitor, that you didn't consider yourself an 3 expert on suicide, are you? 4 A. I never said I was an expert 5 on suicide. Yes, I am telling the jury that. 6 And -- 7 Q. Well -- I'm sorry, I didn't 8 mean to interrupt you. 9 A. I never represented myself as 10 a psychiatrist or an expert on the many different 11 areas that we had to consider. We received 12 consultation on a number of different areas. 13 Q. Was there any expert in July, 14 1985 in this area that was employed by Eli Lilly 15 in-house? 16 A. Expert on suicide? 17 Q. Yes. 18 A. No, I would say no. 19 Q. Was there any expert on 20 depression employed in-house at Lilly at this 21 time, July, 1985? 22 A. There were no psychiatrists at 23 this time, so I would say no. I certainly would 24 not consider myself as an expert on depression. Page 325 1 Q. Was there anybody employed 2 in-house at Lilly that was considered an expert 3 in the relationship between depression and 4 suicide in July, 1985? 5 A. No. 6 Q. Did you consider the 7 investigators that were administering the 8 clinical trials on this antidepressant medication 9 as experts on the subject of depression? 10 A. Yes. 11 Q. Did you consider the 12 investigators that were administering the 13 clinical trials on Prozac, this antidepressant 14 medication, as experts on suicide? 15 A. I did not evaluate them in 16 that sense. In a clinical sense, in that that is 17 a part of the depression, I expected them, and 18 think that they were very knowledgable in that. 19 In the sense of the demographics that Doctor 20 Winokur was there, there are only a few people in 21 the world that have that in-depth knowledge of 22 those issues, and I would not say that all of the 23 investigators had his level of expertise. 24 Q. So it's your testimony to this Page 326 1 jury in these lawsuits, in this lawsuit, that at 2 the time Lilly did this analysis, that they had 3 to call in an outside expert on suicide and 4 depression, and whether or not something was in 5 fact and indeed a suicide attempt or a completed 6 suicide as opposed to relying on the judgment of 7 their investigators that were administering the 8 clinical trials? 9 MR. LORE: I object to the form of the 10 question, that's not what he said. Doctor, you 11 can answer him. 12 A. It's my testimony to the jury 13 that medicine is very complex and the development 14 of drugs is very complex. There were many areas 15 that have nothing to do with this, for instance 16 phospholipidosis, where we sought outside 17 expertise to help us understand complex problems. 18 And we felt, and I would still support, that that 19 is the appropriate way to do things if you don't 20 feel that you're totally competent, that you're 21 not the best resource in the world to sort out 22 such complex issues, yes. 23 Q. But this is an antidepressant 24 medication. Don't you feel that there was some Page 327 1 necessity to have some competence and some 2 expertise in-house on depression since that was 3 the drug that you were investigating that was 4 intended to be marketed to people in this country 5 and throughout the world? 6 A. We had some competence and 7 expertise, we just -- 8 Q. From whom? 9 A. From the people that were 10 involved in the development of the drug. I had 11 learned a lot, and developed a lot of knowledge -- 12 it's a matter of degree. 13 Q. Give me the name of a 14 psychiatrist that was involved in the development 15 of fluoxetine hydrochloride at Eli Lilly and 16 Company. Was Ray Fuller a psychiatrist? 17 A. No, but he's a 18 neuropharmacologist. 19 Q. Was David Wong a psychiatrist? 20 A. No, he's not. 21 Q. Does Ray Fuller hold himself 22 out as an expert in human behavior? 23 A. Only in the pharmacological 24 sense, not as a psychiatrist would. I have never Page 328 1 heard him say that. 2 Q. Is Ray Fuller capable of 3 making a psychiatric diagnosis? 4 A. I don't know that, I would not 5 think so, but I -- 6 Q. In fact Ray Fuller would 7 probably be put in prison if he were holding 8 himself out as a psychiatrist, wouldn't he? 9 A. I know him, and I don't think 10 he would ever do that. 11 Q. Well, that's the point. He's 12 not an expert on psychiatry and human behavior, 13 is he? 14 A. Not in the clinical sense. 15 Q. Is David Wong? 16 A. No. 17 Q. David Wong's not an M.D. 18 A. That's correct. 19 Q. David Wong can't prescribe 20 drugs, can he? 21 A. No. 22 Q. Ray Fuller can't prescribe 23 drugs, can he? 24 A. That's correct. Page 329 1 Q. They're laboratory scientists, 2 aren't they? 3 A. Yes. 4 Q. Is Doctor Leigh Thompson a 5 psychiatrist? 6 A. No. 7 Q. Is he an expert on human 8 behavior? 9 A. I have never heard him say 10 that he is. 11 Q. Is Doctor Robert Zerbe a 12 psychiatrist? 13 A. No. 14 Q. Is he an expert on human 15 behavior? 16 A. I have never heard him claim 17 that he was. 18 Q. Is Doctor Mel Perelman, who 19 was president of Lilly Research Laboratories at 20 this time, a psychiatrist? 21 A. No. 22 Q. Is he a medical doctor? 23 A. No. 24 Q. Can he prescribe medications? Page 330 1 A. No. 2 Q. Does he prescribe medications? 3 A. I don't know. 4 Q. Does he see patients? 5 A. I don't know that. 6 Q. Does Doctor Leigh Thompson see 7 patients? 8 A. I don't know. 9 Q. Did he see patients when you 10 were there? 11 A. Not that I know of. 12 Q. Did Doctor Robert Zerbe see 13 patients? 14 A. Yes. 15 Q. Did he see psychiatric 16 patients? 17 A. Not that I know of. 18 Q. Did he administer psychiatric 19 medications, that you're aware of? 20 A. Not that I'm aware of. 21 Q. You didn't see psychiatric 22 patients when you were there, either, did you, 23 Doctor Wernicke? 24 A. That's right. Page 331 1 Q. And you didn't prescribe 2 psychiatric medications, did you? 3 A. Except in the context that we 4 talked about yesterday, in treating patients at 5 the child neurology clinic. 6 Q. That one occasion where you 7 treated a child with Tourette's syndrome, which 8 was in fact, in all honesty, a neurological, not 9 a psychiatric problem, wasn't it? 10 A. It's considered 11 neuropsychiatric. 12 Q. All right. It's believed to 13 have neurological or organic causes, doesn't it? 14 A. Just like depression, yes. 15 Q. All right. In fact what 16 occurred in this analysis that was done is there 17 were individuals who the Lilly clinical 18 psychiatrists, investigators, had determined were 19 making suicide attempts were being taken to some 20 other expert and being deleted as individuals who 21 made suicide attempts, correct? 22 A. No, that's not correct. 23 Q. Being recharacterized as 24 individuals who did not in fact have suicidal Page 332 1 attention -- intentions. 2 A. No, it's the premise that you 3 started off with that's wrong. These were not 4 all events that were reported as suicide 5 attempts. These -- this is the result of a sweep 6 of anything that we thought could even remotely 7 be considered a suicide. Let me finish, because 8 you did ask the question. These are events that, 9 like injury, when somebody cut their wrist, we're 10 not saying that the investigator classified that 11 as a suicide attempt, they may or they may not 12 have. What we did is we pulled out everything 13 that even remotely, in any sense, could have been 14 an overdose. Whether it was accidental or not, 15 we wanted to cast the broadest net we could. And 16 then we brought in an expert and said now here's 17 what we know, we don't really feel qualified to 18 make this judgment. We did not recategorize what 19 the investigators determined, the term that the 20 investigators gave, and I want to be very clear 21 about that. 22 Q. Wasn't what Doctor Winokur 23 looked at the exact same data that the BGA had 24 already looked at and rejected your application Page 333 1 for in connection with suicide attempts? 2 A. First of all -- 3 Q. Can you answer that question 4 yes or no? 5 MR. LORE: If you can answer yes or 6 no. He doesn't have to answer -- 7 A. The premise is wrong. 8 MR. SMITH: That's why I asked him can 9 he. 10 A. No, I can't, because the 11 premise is incorrect. First of all the BGA did 12 not reject the application, as you well know. 13 Second, there were a number of reasons given, 14 some to do with efficacy, one of them was 15 potential suicides, that led to the intention to 16 reject. So if the premise is correct, then I can 17 answer the question. But yes, these are the same 18 cases, to my knowledge, that were included in 19 that submission, although I'm not -- again, I'm 20 not sure whether -- there may have been more at 21 this time, I don't remember whether these are the 22 exact same ones that were submitted then. 23 Q. Are you trying to mislead this 24 jury, Doctor? Page 334 1 A. Actually, I'm trying to do the 2 opposite, I'm trying very hard to be very clear. 3 Q. Are you trying to tell this 4 jury that what this data is, that was sent to 5 Doctor Winokur, is different data that the BGA 6 had? 7 A. What I'm saying is that this 8 occurred approximately two years later, and what 9 I'm not sure of is whether this hadn't been 10 updated. I would have thought, would have 11 considered everything, and things happen over 12 time, I just don't remember if these are the 13 exact patients or whether there's more here than 14 what was seen by the BGA. 15 Q. Okay, I'll take that then. 16 But are you trying to tell this jury that you all 17 punched in something into your computer system 18 and pulled up something other than what had been 19 reported as an adverse event, that you, for 20 instance, went to free text and tried to draw up 21 something? 22 A. No. What we did is -- 23 Q. You went to something that was 24 characterized as an event term, is that right? Page 335 1 A. Correct. 2 Q. And that event term would have 3 been an event using the Costart or the ELECT 4 terminology or were your investigators allowed to 5 report as event terms accurately what was 6 occurring during the clinical trials? 7 A. They reported what was in the 8 clinical trials, but it had to be -- somehow it 9 had to be given a term, otherwise there was no 10 way to track it. 11 Q. And were they told to report 12 to Lilly suicide attempts as a suicide attempt? 13 A. They were instructed to 14 identify the term, the event, to the best of 15 their knowledge. 16 Q. My question, Doctor Wernicke, 17 is very simple. You were responsible for all 18 U.S. clinical trials on Prozac for a period of 19 time. Were the investigators required to report 20 suicide attempt back to Eli Lilly and Company as 21 suicide attempt? 22 MR. LORE: And he's already given you 23 the answer to that question. 24 MR. SMITH: No, he hasn't. Page 336 1 A. Let me clarify. If they felt 2 it was a suicide attempt, it would have been 3 appropriate to report it as such. We did not -- 4 I don't remember us specifically instructing them 5 to report something the way they saw it. The 6 same would hold up for rash or anything else, if 7 you think this is what it is, this is what you 8 should report it as. But we did not, as I 9 remember, specifically make an issue of suicide 10 attempts. 11 Q. Were your investigators told -- 12 they were not specifically told to report suicide 13 attempt as suicide attempt? 14 A. Not to my knowledge or memory. 15 We did not specificly discuss that as an event, 16 not that I remember. 17 Q. Were they told to report 18 suicide attempt in some other manner? 19 A. No. They were given a 20 dictionary of terms and asked to choose the most 21 appropriate one in their clinical experience. 22 Q. All right. Would you have 23 given any instructions to any of your 24 investigators to report an attempted suicide as Page 337 1 worsening of depression? 2 A. I don't remember giving 3 anybody instructions like that. 4 Q. Would that be appropriate, for 5 an investigator to report what was a suicide 6 attempt as worsening of depression? 7 A. Not as the only event. They 8 may have qualified it as a cause for the 9 potential suicide, but that would never be -- I 10 would never encourage them to report it as such. 11 Q. Would you encourage a clinical 12 investigator to report suicidal ideation, not as 13 suicidal ideation but as depression? 14 A. We instructed the 15 investigators to record the efficacy and to 16 record side effects and adverse events in every 17 regard. If an event was part of the illness, we 18 instructed them to record it as part of the 19 illness. But if they thought that there was an 20 event associated with it, they could also report 21 it as the event. 22 Q. What if a patient came to one 23 of your clinical investigators and said, you 24 know, since I have been in this clinical trial my Page 338 1 depression has gotten worse, and in fact I've 2 started thinking about suicide since I have been 3 in this clinical trial, what is it you're giving 4 me now. Would the investigator in that instance 5 be told to report that as a worsening of 6 depression or as an adverse event of suicidal 7 ideation? 8 A. We did not give specific 9 instructions in specific instances like that. 10 Q. Why not? 11 A. Because these investigators 12 are qualified psychiatrists, and for us to say 13 you should consider this as an event or not is 14 somewhat presumptuous, and we tried very hard not 15 to do that. 16 Q. If they are qualified 17 psychiatrists, Doctor Wernicke, why were you 18 calling in another psychiatrist to second guess 19 them to reduce the number of suicide attempts and 20 suicides? 21 A. Well, again, the premise is 22 wrong. First of all, we did not try to reduce 23 the number, and we did not -- 24 Q. They did -- that's what Page 339 1 happened, wasn't it? 2 A. Let me finish. 3 Q. Well, wasn't that what 4 happened? 5 A. No, not truly, because they 6 did not report all of these as suicide attempts. 7 As I explained before, these were all terms, 8 including terms that related to injury or 9 overdose, that we had considered might even 10 potentially be suicide attempts. So the 11 supposition that the investigators considered 12 these suicide attempts is false, and therefore we 13 did not bring an expert to try to reduce the 14 number. And further, in every area of knowledge, 15 as I'm sure it's true in law, too, there are 16 people that specialize in one particular area. 17 They may all be perfectly competent to practice, 18 but there are people, and there's usually only a 19 few in the country or world, that have that very 20 in-depth expertise. And somebody else has an 21 in-depth expertise on some other issue, and 22 that's why we called in an expert. Not because 23 the investigators were not qualified, and 24 certainly not because we wanted to reduce the Page 340 1 number, because these weren't even all reported 2 to us as suicide attempts. And that needs to be 3 very clear to the jury. 4 Q. Well, was there ever at any 5 time prior to July 1, 1985, an effort made by Eli 6 Lilly to call in somebody that had particular 7 expertise in the relationship of suicide and 8 depression? 9 A. We contacted Doctor Winokur 10 before July 1, 1985. But before this course of 11 consultation, not to my knowledge. 12 Q. Can we say -- since you said 13 you contacted him before July 1, can we say 14 before June 1, 1985 as a date that would be 15 reasonable? 16 A. Sometime that spring or 17 summer. 18 Q. Can we then say, to get this 19 accurate, that before June 1, 1985 Eli Lilly and 20 Company never felt it necessary to call in an 21 expert that had or was holding himself out to be 22 a specific expert on the relationship of suicide 23 and depression? 24 A. All I can say is that I have Page 341 1 no knowledge of any other expert being involved. 2 Q. All right. It's your 3 testimony that these people that Doctor Winokur 4 were reviewing were not individuals who had been 5 reported to you as having made suicide attempts 6 during the clinical trials, but were individuals 7 who had just reported any potential for a suicide 8 attempt? 9 A. Some of them probably were, I 10 don't remember. My testimony is that that was 11 not the only criteria for people to get on that 12 list. I know some of them were, but I'm not sure 13 they all were. 14 (PLAINTIFFS' EXHIBIT NO. 12 WAS 15 MARKED FOR IDENTIFICATION AND 16 RECEIVED IN EVIDENCE.) 17 Q. Why don't you look at Exhibit 18 12, then, maybe that would help you. 19 A. Okay. 20 Q. Exhibit 12 is a document dated 21 April 19, 1985 and authored by you, is it not? 22 A. Yes. 23 Q. And Doctor C.D. Hardison and 24 Doctor R.L. Zerbe are copied in on that. Page 342 1 A. Yes. 2 Q. Are they not? 3 A. Yes. 4 Q. And this has to do with 5 suicides and a tabulation, which eventually ended 6 up being the data that was submitted to Doctor 7 Winokur, correct? 8 A. Yes, that's correct. 9 Q. Look with me at the -- and it 10 talks about the fact that you're going to send 11 this material to Doctor Winokur or an outside 12 consultant, doesn't it? 13 A. Yes. 14 Q. Look with me at the second 15 sentence of the second paragraph. Don't you 16 there say, in quote, in preparing this material, 17 all people who were reported to have had a 18 suicide attempt were included, end quote? 19 A. Yes, it says that. 20 Q. You say all people who were 21 reported to have had a suicide attempt in that 22 letter, don't you? 23 A. Yes, those are the words, 24 uh-huh. Page 343 1 Q. All right. 2 (PLAINTIFFS' EXHIBIT NO. 13 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. Now, Exhibit 13 is a document 6 dated October 8, 1986 authored by you, is it not? 7 A. Yes. 8 Q. And at that time you had some 9 more data and some more reports of suicides and 10 suicide attempts, didn't you? 11 A. Yes. 12 Q. And this was also going to be 13 used in connection with the issue raised by the 14 German government, and at that time the British 15 government. 16 A. I don't remember about the 17 British government. It may be, I just don't 18 remember that they asked that question, but they 19 might have. 20 Q. All right. Well, it's going 21 to Mr. Brockwell in Erl Wood, is it not? 22 A. Yes. 23 Q. And Erl Wood is in England. 24 A. Yes, but that was the European Page 344 1 research arm, they were responsible for all of 2 Europe. That does not imply that this was for 3 the UK. 4 Q. It was certainly for Germany. 5 A. Yes. 6 Q. And again, there's been more 7 collection of more suicide attempts during the 8 clinical trials, hasn't there? 9 A. Yes. 10 Q. This is October 8, this is a 11 year and a half after this Winokur analysis, 12 isn't it? 13 A. Yes. 14 Q. And the issue is still pending 15 before the BGA and the Commission A in Germany, 16 isn't it? 17 A. Yes. 18 Q. And you're still going over 19 this data, correct? 20 A. Yes. 21 Q. And look with me. You mention 22 this earlier analysis, don't you, in this letter? 23 A. Can you point out what you're 24 referring to? Page 345 1 Q. Look at the third paragraph, 2 about the middle of the paragraph. You say some 3 of the cases were clearly not attempts, although 4 included on the list. I think that perhaps we 5 should eliminate some of them and never submit 6 them with the others. Doctor Winokur did 7 something similar with the previous list. We 8 could do that again, but it is very time 9 consuming if done with a consultant, and we would 10 need all the CRFs before we even started. My 11 feeling is that we can make a judgment and state 12 (internally) why we eliminated that case, end 13 quote, correct? 14 A. Where? I'm not sure I see 15 where you are. You're on item number three? 16 Q. I'm in paragraph number three, 17 page one. 18 A. I'm afraid we're not on the 19 same page again. 20 MR. SMITH: Let's take a break. 21 (A SHORT RECESS WAS TAKEN.) 22 Q. Doctor Wernicke, I apologize 23 for inadvertently giving you the wrong document 24 to look at. I think we're now back on the same Page 346 1 wavelength, and in fact I've got some yellow 2 markings near where I was reading before we went 3 off the record and I'll repeat that. It says 4 some of the cases were clearly not attempts, 5 although included on the list. I think perhaps 6 we should eliminate some of them and never submit 7 them with the others. Doctor Winokur did 8 something similar with the previous list. We 9 could do that again, but it is very time 10 consuming if done with a consultant, and we would 11 need all the CFRs before we even started. My 12 feeling is that we can make a judgment and state 13 (internally) why we eliminated that case, 14 correct? 15 A. Yes. 16 Q. All right. So you're talking 17 eighteen months later about the fact that Doctor 18 Winokur reviewed this data and eliminated some. 19 A. Yes. 20 Q. This is more data included in 21 this October '86 letter, isn't it? 22 A. Yes. 23 Q. And you say now what we'll do 24 is instead of using Doctor Winokur, we'll go over Page 347 1 this list and we can eliminate some internally. 2 A. Yes. 3 Q. But earlier, you had felt that 4 you would need an expert to review this material. 5 A. This was a year and a half 6 later. 7 Q. All right. And you didn't 8 feel that you needed that expert again. 9 A. Well, we preferred to have it, 10 that's why I made the comment that we could do 11 that. But we were under a considerable time 12 pressure, and as I said here, I just didn't feel 13 that we could get all that done. 14 Q. Considerable time pressure to 15 do what? 16 A. To get this material together 17 to make a submission. 18 Q. I'm not seeing any document. 19 Are you aware of a document that was issued by 20 the BGA or the German regulatory body requiring 21 that you produce something within a short time of 22 October, 1986? 23 A. No, I don't remember any such 24 document. Page 348 1 Q. Where was the time pressure 2 coming from, Doctor Wernicke? 3 A. What I remember about this is 4 that we were trying to meet a submission 5 deadline. I don't know exactly where that 6 pressure was coming from. 7 Q. A submission where? 8 A. To the BGA to get this 9 material together. 10 Q. The product wasn't approved in 11 Germany for another, in fact, three years and two 12 months. 13 A. Yes. 14 Q. So where was the time pressure 15 coming from? 16 A. That, I'm not aware of. I 17 remember a deadline that we had that we were 18 trying to get all the material together by. 19 Q. You don't reflect any time 20 pressure on what you're writing here. 21 A. I do. 22 Q. Where? 23 A. It says, and we could -- we 24 could do that again, but it is very time Page 349 1 consuming if done with a consultant, and we would 2 need all the CRFs before we started. That's what 3 jogged my memory, that we were trying to get all 4 of this together. That's why I know there was a 5 time pressure, and I remember now. 6 Q. What was the time pressure? 7 Obviously it would be time consuming to gather a 8 lot of people together and to resubmit it to 9 Doctor Winokur, but I don't see any situation 10 back in this review of Doctor Winokur's data 11 where he didn't get back to you within a 12 relatively short period of time, did he? 13 A. That's true, at that time he 14 got back. 15 Q. He responded real quickly, 16 didn't he? 17 A. It appears that way. 18 Q. So who was putting time 19 pressure on you? 20 A. All I knew was -- and I don't 21 remember the dates -- we were expected to have 22 this information ready by a certain date and that 23 date was coming up. And we were working with all 24 the affiliates worldwide to get all this Page 350 1 information together and that's reflected in what 2 I said there. 3 Q. Was this pressure being put on 4 you by any regulatory body, Doctor Wernicke, or 5 was this pressure being put on you within the 6 corporation to get this product approved so it 7 could be marketed in these other countries so you 8 could sell the product and generate income from 9 these countries? 10 A. Regulatory agencies in Europe, 11 outside the U.S., never put direct pressure on me 12 to do anything because I did not interact with 13 them directly, everything went through the 14 affiliates. So I don't know whether there was a 15 deadline imposed by the BGA, whether it was 16 internal, that I just didn't know. What I 17 remember about this is that we, from whatever 18 source, had a deadline we wanted to meet, and I 19 don't know how that was generated. 20 Q. All right. So your testimony 21 is the reason in October of 1986 you didn't call 22 Doctor Winokur in is because you didn't have 23 time? 24 A. We didn't want to take the Page 351 1 time, we weren't sure we could get it done. But 2 we also felt, having learned from the way he did 3 it and having now a year and a half experience, 4 that we were in a better position, as long as we 5 documented everything that we did and why we did 6 it, that we could make a similar judgment on the 7 individual cases, as long as the documentation 8 and the reasoning was maintained. That's the way 9 I remember making that decision. 10 Q. I don't see any psychiatrist 11 copied in on this October, 1986 letter, Doctor 12 Wernicke, are there? 13 A. No. 14 Q. Doctor Wernicke -- I mean 15 Doctor Winokur -- let's go back to Exhibit 12 to 16 the set of material where he was reviewing these 17 reports from the clinical investigators. 18 A. I believe that's Exhibit 11. 19 Q. I'm sorry, Exhibit 11. I 20 don't see anywhere here, Doctor Wernicke, where 21 Doctor Winokur has called any particular 22 investigator to get any particular details 23 concerning any of these cases that he's reviewed. 24 Do you see anything such as that? Page 352 1 A. No. 2 Q. It wasn't done, was it? 3 A. I don't see anything to that 4 effect. I can't tell you what Doctor Winokur 5 did. 6 Q. Well, did you ever talk to any 7 of your clinical investigators that told you they 8 had had discussions with Doctor Winokur 9 concerning these particular instances where there 10 was a question concerning whether or not there 11 was indeed a suicide attempt? 12 A. I don't remember anybody 13 telling me that, no. 14 Q. And you don't know -- you and 15 Doctor Winokur certainly didn't discuss any 16 conversations that Doctor Winokur might have had 17 with any of your psychiatrists, investigators, 18 who had actually observed these actions and 19 reactions by these patients? 20 A. True, I don't remember -- know 21 of any such conversations. 22 Q. Can't you say with pretty much 23 confidence that this is something that Doctor 24 Winokur did on his own? Page 353 1 A. It's not my role to make 2 suppositions about what other people did, I can 3 only deal with the facts that I know. 4 Q. Did you ever give any 5 instructions to Doctor Winokur that if there's a 6 question about this, what you should do first is 7 talk to our clinical investigators who are 8 psychiatrists, who we've instructed to run our 9 clinical trials, and get from them their input 10 and their information concerning their in person, 11 face-to-face observations of these individuals? 12 A. I did not give Doctor Winokur 13 any specific instructions as to how he was to 14 approach his analysis. I gave him the material, 15 said you are an expert on suicide, help us 16 evaluate this. 17 Q. You think that that would have 18 been something appropriate for him to do in 19 getting some insight into these individuals that 20 these events had been reported on, is to talk 21 with the physician that was actually making these 22 recordations and actually making these 23 observations and knew these people and had had 24 in-person visits with these people? Page 354 1 A. I would not presume what would 2 be appropriate for a full professor in psychiatry 3 to do in regards to evaluating cases. I don't 4 think that would be appropriate for me to presume 5 what he should or should not have done. 6 Q. Let me ask you something, 7 then. Don't you think it's appropriate to gather 8 the best and the most complete data and 9 information concerning a particular event before 10 making some scientific judgment? 11 A. What we asked Doctor Winokur 12 to do, which I think is appropriate, is to look 13 at the material and make a judgment. If he felt 14 that he needed more information, he was certainly 15 free to do that, directly to the investigator or 16 even the patient. We did not instruct him how to 17 come to a conclusion, that is up to him as the 18 expert. So I would not -- 19 Q. Is that what I asked you, 20 Doctor Wernicke? 21 A. As I remember, it was rather 22 convoluted so I'm not quite sure. 23 Q. Why don't we have the question 24 read back to you and let you listen to it again, Page 355 1 and I bet you can work through any convolutions 2 of the question and answer it a little more 3 directly this time. 4 MR. LORE: I object to whatever that 5 was, jury argument, jury statements, instructions 6 to the witness, whatever. 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED TESTIMONY.) 9 A. My answer remains the same, 10 and that is that we gave Doctor Winokur the 11 material and asked him to evaluate it without 12 specific instructions as to how to do it. If he 13 felt he had the information, then that would be 14 appropriate. If he felt he didn't, he was 15 certainly free to seek whatever information from 16 us or the investigator that he wanted. So I 17 don't know that the question is really relevant, 18 except in a very broad context. 19 Q. We'll see what the jury -- 20 whether the jury thinks it's relevant or not. 21 MR. LORE: I object to the statement, 22 that's not a question to the witness, it's more 23 of a harassment of the witness. 24 Q. My question to you was what Page 356 1 you believe concerning the scientific inquiry and 2 making a scientific opinion as a physician and a 3 scientist. Isn't it best to have as complete 4 information as is possible concerning a 5 particular observation in order to render 6 scientific judgment on a matter such as this? 7 A. I can only tell you what I 8 would do, and I can't presuppose what is right 9 and wrong. If I'm asked to give judgment and 10 make some assessment, I look at the material I 11 have. If I have further questions, I will 12 certainly get more information. The problem is 13 when do you have all the information, that could 14 go on forever. There is a point when one has to 15 say yes, I believe I can make a judgment, and 16 that is no strict guideline that can be imposed. 17 Q. Let me ask you this, Doctor 18 Wernicke: Did you call any of the investigators 19 to ask them what their feeling was concerning 20 whether or not what they were reporting as a 21 suicide attempt or a suicide was indeed a suicide 22 attempt or a suicide? 23 A. I don't remember calling any 24 investigator about specific cases. Page 357 1 Q. At any time? 2 A. At any time. 3 Q. At anyplace? 4 A. Not with my initiating the 5 call. When I received calls, we discussed it, 6 but I was always very careful, and this was a 7 conscious act not to put words or ideas into the 8 mouth or head of investigators. I basically 9 listened, I said tell me what you see and let me 10 write it down. There's always a danger that the 11 listener can reinterpret and by conversation move 12 or somehow alter the perception, and we were very 13 careful -- and I know that was always my own 14 personal objective, was to be a recorder of what 15 there was. 16 Q. So what had been reported, as 17 far as you know, was carefully and accurately 18 recorded and it was independent from any bias 19 that might have occurred in-house at Lilly. 20 A. That's correct. 21 Q. All right. And this was the 22 data that Doctor Winokur was reviewing. 23 A. Right. 24 Q. Go with me on to, is it, Page 358 1 Exhibit 10 or 11? 2 A. Eleven. 3 Q. Go to page three of his letter 4 of July 11th. Did I say July? I meant July 2nd, 5 where there's analysis case by case. 6 A. Page three? 7 Q. Case by case. 8 A. Right, but on -- you said on 9 page three? 10 Q. Yes. The three is right under 11 July 2nd. 12 A. Yes, I have it. 13 Q. Go to item five, would you? 14 A. Uh-huh. 15 Q. There it says, the patient had 16 considerable suicide ideation prior to the onset 17 of the study. The suicide attempt was by wrist 18 slashing. This patient stopped medication March 19 13th, and the suicide attempt was March 15th. As 20 the half life of the drug is three dash four 21 days, we agreed this, in fact, could be related 22 to the drug, correct? 23 A. That's what it says, yes. 24 Q. And that's Doctor Winokur's Page 359 1 analysis? 2 A. I believe this is his, yes. 3 Q. And Doctor Winokur is the 4 worldwide expert consultant called in by Lilly to 5 make an analysis of this issue, right? 6 A. Yes. 7 Q. And there he is stating that 8 in this instance the suicide attempt was in fact 9 related to the drug, wasn't he? 10 A. No, that's not what he's 11 saying. 12 Q. That's what is written there, 13 isn't it? 14 A. We agreed that this, in fact, 15 could be related to the drug. That's not what 16 you just said. 17 Q. That's not what I just said? 18 A. Absolutely not. 19 Q. I didn't -- 20 MR. LORE: No, you did not say that. 21 Q. Let's read it right again. As 22 the half life of the drug is three-four days, we 23 agreed that this in fact could be related to the 24 drug, end quote, correct? Page 360 1 A. That is what it says. 2 Q. Did you talk with Doctor 3 Winokur about the fact that in this instance he 4 found that this in fact is -- suicide attempt, in 5 fact, could be related to the drug? 6 A. I don't remember talking about 7 this particular case. 8 Q. Well, here he's the expert. 9 A. I see that, but you asked me 10 if I talked to him about that, and I'm telling 11 you I don't remember whether I discussed this 12 particular case among all the others. 13 Q. Did you talk to him about any 14 particular case that he's listed here in this 15 letter? 16 A. They came in and we had a 17 meeting and we reviewed cases and they told us 18 about the ones that they -- were not -- that 19 there was no absolute concensus on -- that there 20 was no absolute concensus on or the ones that 21 they disagreed, perhaps, were not suicide 22 attempts or that definitely were. But I don't 23 remember the word-by-word discussion about each 24 individual case. Page 361 1 Q. Did you have any discussion 2 about these eight cases that he mentions in his 3 letter? 4 A. As I said, we discussed many 5 cases, and I don't remember in that meeting which 6 case we discussed and what we said about 7 individual cases. 8 Q. Don't you find that that's of 9 some significance, that you would call in this 10 worldwide expert to consult with you on this 11 issue as to whether or not Prozac could be 12 related to suicidality, and he makes the 13 conclusion, as that expert, on this particular 14 suicide attempt that this in fact could be 15 related to the drug? 16 A. What -- 17 MR. LORE: I object to the form of the 18 question. I mean is it following from the last 19 question you asked, Paul? 20 Q. Yes, did you ask him about 21 this incident? 22 MR. LORE: He's already told you he 23 can't remember specifically, so I object to the 24 form of the question. He's already answered Page 362 1 that, he doesn't remember any specific case. 2 Q. Did you read his analysis that 3 he sent to you, Doctor Wernicke? 4 A. Yes, I did. 5 Q. You didn't believe, when you 6 received this letter, did you, that -- or up to 7 the time you received this letter, that Prozac 8 could be related to a particular suicide attempt, 9 did you? 10 A. I didn't believe it then and I 11 don't believe it now, I have no scientific 12 evidence to make me come to that conclusion. 13 Q. But here you have an expert 14 that's telling you in a letter that in fact this 15 particular suicide attempt could be related to 16 the drug, don't you? 17 A. Could be. And he is talking -- 18 if you look at the immediately preceding 19 sentence, he's talking about the half life of the 20 drug. What he's saying is that the drug was 21 still in the body at that time, he's not making a 22 causal relationship. See, one has to take this 23 whole paragraph together. What he's saying is 24 the drug is still there, this happened, you can't Page 363 1 say the drug is gone. That's how I read that, my 2 interpretation of what he said. 3 Q. Well, all I can do is read the 4 sentence as is written here. 5 A. That's all I do, too. 6 Q. And it says as this half life 7 of the drug is three to four days, we agreed, in 8 fact -- we agreed that this -- I assume he was 9 talking about the suicide attempt. He says 10 that's the analyses he's making, and that's the 11 issue that is being raised by the BGA, and it's 12 supposedly the issue being investigated by Eli 13 Lilly, isn't it? 14 A. Yes. 15 Q. And he says that this, in 16 fact, could be related to the drug, correct? 17 A. That's correct. 18 Q. Was this analysis sent to the 19 United States Food and Drug Administration, 20 Doctor Wernicke? 21 A. I don't know whether this was 22 sent. 23 Q. Should this have been sent to 24 the United States Food and Drug Administration? Page 364 1 A. Not necessarily. Our criteria 2 for sending information, we included submissions, 3 we sent submissions that came from foreign 4 governments, we submitted an annual and periodic 5 reports, pertinent information that we had in 6 relationship to questions or that changed our 7 understanding of the drug. Those were the 8 criteria for submission to the FDA. So I'm not 9 sure I can say whether this should or should not 10 have been submitted. 11 Q. This report relates to the 12 safety of the drug, doesn't it, Doctor Wernicke? 13 A. Yes, but it doesn't change our 14 conclusion that I specifically qualified it. And 15 those, in fact, are the criteria that you should 16 submit, what pertinent information that changes 17 our understanding of the drug. 18 Q. Is it your testimony, Doctor 19 Wernicke, that it was Eli Lilly and Company, or 20 at least your policy in connection with reporting 21 to the FDA only information that changed your 22 conclusion about the safety of the drug? 23 MR. LORE: I object to the form of the 24 question, that's not his testimony. You can go Page 365 1 ahead and answer it, Doctor. 2 A. If you look at the regulations 3 for what is to be submitted to the FDA, it very 4 clearly states that you are to submit any 5 information that you have that alters, that 6 impinges or alters the perception and the 7 knowledge of the safety and efficacy of that 8 drug, and we tried to follow that as best as we 9 could at all times. 10 Q. Who is making the 11 determination as to whether or not it alters the 12 perception of the safety and the efficacy of the 13 drug, Lilly? 14 A. Yes, because we are the ones 15 submitting that information. 16 Q. So in that instance, you're 17 controlling what information the United States 18 Food and Drug Administration has in evaluating 19 this drug because you're making the decision at 20 Lilly whether or not this alters the -- what's 21 known about the safety and efficacy of the drug. 22 A. We submitted all of the 1639s, 23 all of these reports. You asked me specifically 24 about this interpretation, this summary, and that Page 366 1 would be a judgment call, that is correct. 2 Q. All right. See, what I want 3 to know is, since you call this Doctor Winokur in 4 as a worldwide expert on suicide, as somebody 5 particularly knowledgable on suicide, I'm just 6 interested in whether or not you would find it 7 appropriate to let the United States Food and 8 Drug Administration have his opinion concerning 9 this issue. 10 A. Certainly if there was any 11 question from the FDA or if, in fact, we found 12 that there was some change in the rate in 13 relationship to fluoxetine, then in that 14 situation I would find it pertinent to include 15 this information. 16 Q. No. Didn't you find it 17 pertinent what Doctor Winokur said? 18 A. Yes, absolutely. 19 Q. And don't you think it would -- 20 that the United States Food and Drug 21 Administration should have as much information 22 concerning this drug as Lilly does? 23 A. In the sense I looked at his 24 conclusion as basically the bottom line, but what Page 367 1 came out of all of this, which -- and what came 2 out of it was that there was no evidence that 3 fluoxetine was associated with an increased risk 4 of suicide. So that did not change our 5 perception and the information that we had. 6 Q. Well, if it's beneficial to 7 you, why not give it to the United States Food 8 and Drug Administration? 9 A. Because they're very clear or 10 quite clear about what they want, and we had 11 volumes of all sorts of information. One thing 12 that the FDA complains about is a flood of 13 information or sometimes even thought of as 14 malicious compliance, which we tried not to do. 15 We tried do give them information they asked for, 16 that we felt we should, not to send them a copy 17 of everything we had and make them sort it out. 18 Q. I don't have an extra copy 19 with me, Doctor Wernicke, but I would like to 20 read with you what has been marked in evidence in 21 a number of these other depositions. 22 MR. SMITH: Mr. Lore, this is the 23 approvable letter issued by the United States 24 Food and Drug Administration dated September 9, Page 368 1 1987. 2 Q. You were still employed by 3 Lilly at that time? 4 A. Yes. 5 Q. Were you still director of 6 clinical investigations at that time? 7 A. In some -- actually not, as I 8 remember. We had segmented the studies into 9 different indications, and I wasn't directly 10 supervising the studies. 11 Q. You were involved in Prozac, 12 though, weren't you? 13 A. Yes. 14 Q. And you were delighted to get 15 the approvable letter. 16 A. Certainly. 17 Q. Look with me on page seven of 18 the approvable letter, and I'm just going to read 19 this to you, but I want you to read this with me. 20 A. Okay. 21 Q. It's headed as to what needs 22 to be done following this approvable. See this 23 is dated September 9, 1987, but that didn't give 24 Lilly the right to market the drug, did it? Page 369 1 A. No. 2 Q. That's not final approval. 3 A. That's correct. 4 Q. That's notification by the 5 United States Food and Drug Administration that 6 the product will be approved. 7 A. If all the following are 8 answered. 9 Q. If certain things are done, 10 correct? 11 A. Yes. 12 Q. And one of the things that 13 they asked to do, Lilly to do, is number five 14 here, report on actions taken by other national 15 drug regulatory authorities, correct? 16 A. Yes. 17 Q. And the BGA is another 18 national drug regulatory body, isn't it? 19 A. Yes. 20 Q. It says -- and this is the FDA 21 speaking, right? 22 A. Yes. 23 Q. It says we require a review of 24 the status of all fluoxetine actions taken or Page 370 1 pending before foreign regulatory authorities. 2 Approval actions can be noted, but we ask that 3 you describe in detail any and all actions taken 4 that have been negative, supplying a full 5 explanation of the views of all parties and the 6 resolution of the matter, end quote, does it not? 7 A. Yes. 8 Q. So in the approval letter, 9 specifically -- 10 A. Approvable. 11 Q. Approvable letter, 12 specifically the United States Food and Drug 13 Administration was wanting you to report on other 14 regulatory actions, correct? 15 A. As they do with every drug, 16 yes, that's a standard requirement. 17 Q. What do you suppose the reason 18 for that is, Doctor Wernicke? 19 A. That they wanted to know what 20 happened with other governments. 21 Q. And they want to know before 22 they give you final approval, don't they? 23 A. I would presume that. 24 Q. Because they feel or isn't it Page 371 1 known that the United States Food and Drug 2 Administration, at least in this letter, is 3 requesting information that you have concerning 4 concerns of other regulatory bodies? 5 A. I would not presume what they 6 mean. 7 Q. Let's read what they say. 8 MR. LORE: It says what it says, Paul. 9 A. They want to know what else 10 has happened in the world, whether it's approved, 11 disapproved, why not. 12 Q. And they say in the negative, 13 supplying a full explanation of the views of all 14 parties, doesn't it? 15 A. Yes. 16 Q. Okay. Isn't this view 17 expressed by Doctor Winokur, your expert view of 18 a party? 19 MR. LORE: I object to the question, I 20 don't know how you're making the connection 21 between what's said in here and here, I just -- I 22 don't understand it at all. But Doctor, if you 23 can. 24 A. I think I understand. I'm not Page 372 1 sure that necessarily he would be considered a 2 party. I suppose he could, but I do not have an 3 opinion on that. 4 Q. At this time, in September of 5 1987, the German government has issued an intent 6 to reject letter, have they not? 7 A. Yes. 8 Q. And the action is still 9 pending before Germany, isn't it? 10 A. Yes. 11 Q. And they're still taking a 12 negative view concerning Prozac and the risk of 13 suicide in connection with Prozac, are they not? 14 A. I'm not sure that they 15 expressed anything else since that letter. When 16 you say still taking a negative view, the last 17 thing I remember is that issue of the intent to 18 reject, and I'm not sure whether there was back 19 and forth since then. 20 Q. In fact you never received 21 anything from the German government that said 22 we're not concerned about the risk of suicide any 23 longer, did you? And you, I mean Lilly. 24 A. Well, I did not. Page 373 1 Q. So there was a negative view, 2 or you felt there was a negative view held by 3 Germany because they weren't approving your 4 product, right? 5 A. They did approve the product. 6 Q. They hadn't at this time. 7 A. Not at this time, that's 8 correct, that's correct. 9 Q. And what the Food -- the 10 United States Food and Drug Administration is 11 telling you there is they want to know about 12 this, don't they? 13 A. Yes, they want to know about 14 everything that's happened. 15 Q. All right. And isn't this 16 something that's happened and wouldn't this be 17 something under that that should be submitted, 18 this Doctor Winokur report, something that should 19 be submitted to our government here in the United 20 States to let our government know what your 21 experts think about suicidality and Prozac? 22 A. We certainly submitted to the 23 FDA all the correspondence and communication with 24 the BGA. What went behind that, what was Page 374 1 actually submitted, I just don't know. 2 Q. Well, was this letter of 3 Doctor Wernicke submitted to the BGA? 4 A. Winokur. 5 Q. Winokur, submitted to the BGA, 6 do you know? 7 A. As I told you yesterday, we 8 send things to their German affiliate and they 9 prepare the submission, so I -- 10 Q. Lilly in Indianapolis just 11 shipped it over there and whether the German 12 affiliate does the appropriate regulatory 13 compliance is up to them? 14 A. All I can say is what I saw. 15 And at what point it left my area, my desk, what 16 checks and balances there were after that, I 17 cannot speak to because I was not involved. 18 Q. Did you talk with anybody at 19 the United States Food and Drug Administration 20 about this issue, Doctor Wernicke? 21 A. Not to my memory. 22 Q. Never did you talk? 23 A. I don't remember talking to 24 them. Page 375 1 Q. Never did you talk to anybody 2 about this? 3 A. I'm not saying I didn't, I 4 don't remember specific conversations. 5 Q. Did you ever talk to anybody 6 at the United States Food and Drug Administration 7 and mention this report of Doctor Winokur's? 8 A. I don't remember any such 9 conversation. 10 Q. Were you aware after the 11 approvable letter was sent that the United States 12 Food and Drug Administration was requiring that 13 Lilly send to them all information concerning 14 negative findings by foreign regulatory bodies? 15 A. Yes, I knew that that was a 16 standard paragraph in approvable letters. 17 Q. So you knew -- 18 A. Yes. 19 Q. -- that the Food and Drug 20 Administration is concerned about this issue 21 across the board? 22 A. My reading is that they want 23 to know what's happened. 24 Q. Why is that? Page 376 1 A. Because that's their job. 2 Q. What? 3 A. To know what's happening, to 4 make -- to consider all the information to make 5 their final judgment, that was my understanding 6 of what the FDA's job was. 7 Q. What's your understanding of 8 why the United States Food and Drug 9 Administration finds actions of foreign 10 regulatory bodies significant or of interest? 11 A. My understanding of that is 12 that that is a parallel group that's essentially 13 their counterparts in other countries and that 14 events may have happened there that did not occur 15 in the United States and they may find that of 16 interest or importance. 17 Q. So what happens in foreign 18 countries is important in connection with the 19 safety of the drug? 20 A. Yes, certainly, in terms of 21 exposure and what is found, absolutely. It all 22 goes into the same data base, as it does in the 23 DEN system. 24 Q. A scientist is a scientist, be Page 377 1 he residing in the United States or be he 2 residing in Germany or be he residing in Japan? 3 A. Correct. 4 Q. And there's no guarantee that 5 the United States scientists are better than 6 German scientists on any particular issue at any 7 particular time, is there, Doctor Wernicke? 8 A. No, that's correct. 9 MR. SMITH: Let's take a quick break. 10 (A SHORT RECESS WAS TAKEN.) 11 Q. Doctor Wernicke, was there 12 ever an outside consultant, any worldwide expert, 13 called in on violent aggressive or homicidal 14 behavior during the Lilly clinical trials of 15 which you're aware? 16 A. Certainly not when I was 17 there, and I'm not aware of any. 18 Q. As far as you know, nobody at 19 Lilly ever called in an outside consultant to 20 examine independently whether or not Prozac could 21 cause homicidal behavior? 22 A. That's correct. 23 (PLAINTIFFS' EXHIBIT NO. 14 WAS 24 MARKED FOR IDENTIFICATION AND Page 378 1 RECEIVED IN EVIDENCE.) 2 Q. Doctor Wernicke, I'll tell you 3 for your edification what you have before you as 4 Exhibit 14, and is a review and evaluation of the 5 clinical data, safety update, for Prozac done by 6 the United States Food and Drug Administration 7 signed by Doctor Richard Kapit, M.D. 8 A. Yes. 9 Q. What is the safety update? 10 And I'm not going to ask you about all of this, 11 obviously, but for the jury's benefit, what is a 12 safety update? 13 A. In my understanding, that this 14 is the FDA's summary of their findings regarding 15 the safety of the drug. 16 Q. This appears to have been done 17 sometime in October of 1986? 18 A. This specifically appears to 19 refer, I take it from the first paragraph, in 20 relationship to a large safety update and 21 analysis that we submitted in 1986. 22 A. All right. 23 Q. So what the Food and Drug 24 Administration is doing is they're reviewing Page 379 1 safety information that has been provided to them 2 by Eli Lilly and Company. 3 A. Correct. 4 Q. Is it correct, Doctor 5 Wernicke, that the United States Food and Drug 6 Administration did not themselves conduct any 7 independent clinical trials of Prozac that you're 8 aware of? 9 A. Not clinical trials, no. 10 Q. And all the information that 11 they had concerning clinical trials and the 12 effect of Prozac on humans as demonstrated by the 13 clinical trials, would have been information that 14 had been supplied to them by Lilly. 15 A. The only exception would be, 16 and I don't know that this ever occurred, anybody 17 could submit a 1639 to the FDA and I can't say 18 with any certainty that somebody did not do that 19 and not submit it to us. The potential is there, 20 but I don't know of that ever happening. 21 Q. Let's talk about how great 22 that potential is -- 23 A. I would think very small. 24 Q. -- because in October of 1986, Page 380 1 Lilly -- Prozac wasn't marketed anywhere else in 2 the world, was it? 3 A. Correct. 4 Q. And Lilly had the patent on 5 Prozac, fluoxetine hydrochloride, at that time, 6 correct? 7 A. Correct. 8 Q. So nobody else can use it 9 without getting it from Lilly, unless they 10 committed some illegal act. 11 A. Correct. 12 Q. Or some patent infringement, 13 correct? 14 A. Correct. 15 Q. And Lilly, certainly at that 16 time and probably still today, goes to some 17 lengths to protect their patents, correct? 18 A. Correct. 19 Q. And a patent on Prozac is an 20 extremely valuable asset, is it not? 21 A. I would think so. 22 Q. All right. So, Doctor Kapit 23 is reviewing this clinical trial data submitted 24 by Lilly to them, is he not? Page 381 1 A. Yes. 2 Q. And this contains one hundred 3 and sixteen volumes of information. 4 A. Yes. 5 Q. That was generated by Lilly 6 and submitted to the Food and Drug 7 Administration. 8 A. Yes. 9 Q. None of -- was any of this a 10 hundred and sixteen volumes what you earlier 11 characterized as malicious filings? 12 A. We don't think so, I don't 13 believe so. For malicious compliance, we tried 14 not to do that. 15 Q. All right. Go with me to the 16 last page. Section six point four discusses 17 other adverse effects, does it not? 18 A. Yes. 19 Q. And it says the following 20 adverse effects occurred in association with 21 fluoxetine, but there is no evidence to suggest 22 that they may be caused by the drug, correct? 23 A. Yes. 24 Q. And it lists a variety of Page 382 1 adverse effects that have been reported by Lilly 2 during the clinical trials, correct? 3 A. Yes. 4 Q. And in the fourth paragraph 5 there is adverse effects of bizarre homicidal and 6 suicidal behavior, suicide thought-blocking, et 7 cetera, correct? 8 A. Yes. 9 Q. My question is directed to the 10 bizarre homicidal behavior that's listed there. 11 How many instances of bizarre homicidal behavior 12 were you aware of that occurred during the Prozac 13 clinical trials? 14 A. I can't think of a specific 15 instance that that refers to because that's not -- 16 I don't remember that being a term. This is a 17 description, but I honestly don't remember any 18 specific number or events that that describes. 19 Q. Is homicidal behavior listed 20 in the Costart or ELECT dictionary? 21 A. As I remember it, yes, but 22 there are many, many terms in it and I just don't 23 remember how that's phrased exactly. 24 Q. Are there any event terms in Page 383 1 the Costart or ELECT dictionary that map to 2 homicidal behavior? 3 A. Again, as I remember, there 4 are, but I don't know what they are and I'm just 5 not sure of the details of that specific complex 6 of terms. I would have to look back in the 7 Costart dictionary to be sure. 8 Q. Do you recall any instances of 9 homicide that occurred during the clinical 10 trials, Doctor Wernicke? 11 A. Yes, I remember a case of 12 somebody being shot. 13 Q. By an individual? 14 A. Yes, by another individual. 15 Q. In the clinical trials? 16 A. Well, it turns out, I believe, 17 as I remember, he was not taking the drug, he was 18 in either the placebo phase or the lead-in phase. 19 For some reason it turned out -- well, I'm sorry, 20 wait a minute. I believe the patient was shot, 21 but the person who shot him was not a patient, as 22 I remember. I'm trying to recreate this from 23 memory, a long time ago. 24 Q. So that couldn't be what Page 384 1 Doctor Kapit is speaking of. 2 A. No, I would not think so. 3 Q. It must be some other instant 4 or instances which you're not aware -- 5 A. Or don't remember. 6 Q. -- of homicidal behavior that 7 occurred during the Prozac clinical trials. 8 A. Correct. 9 Q. Do you know of any 10 investigation that was done in those instances of 11 homicidal behavior that occurred during the 12 Prozac clinical trials? 13 A. Not at this time and certainly 14 not that I was involved in. 15 Q. Do you know of any consultants 16 that were called in to examine these instances of 17 homicidal behavior that were reported during the 18 Prozac clinical trials? 19 A. I'm not aware of any. 20 Q. Is the term "bizarre behavior" 21 contained in the ELECT or Costart dictionary? 22 A. I don't remember that it is. 23 But again, I would qualify that there are 24 thousands of terms in there and I don't remember Page 385 1 them all, I would just have to look it up. 2 Q. Do you know why there would be 3 a characterization of this homicidal behavior 4 that occurred during the Prozac clinical trials 5 as being bizarre homicidal behavior? 6 A. I don't know why that choice 7 of words would have been used. 8 Q. Certainly he's reading it -- 9 he's quoting what are event terms, specific event 10 terms, it appears, doesn't it? 11 A. I'm not sure, I'm not sure 12 whether that's an event term or his 13 interpretation having looked at the description 14 of the event, because those were also available 15 to him, of course. Not just the terms, the 16 actual reports and the descriptions. 17 Q. Have you ever seen any actual 18 reports or descriptions of homicides that 19 occurred during the clinical trials, other than 20 that one where somebody, as you report it, was 21 the shootee instead of the shooter? 22 A. I don't remember specific 23 cases. 24 Q. Are you aware of homicidal Page 386 1 violent aggressive behavior toward others being 2 linked to serotonin, either in reducing that type 3 of behavior or increasing that type of behavior? 4 A. No. 5 Q. Do you know of any 6 investigations or scientific papers that have 7 been written in connection with the role of 8 serotonin in impulsivity as it might relate to 9 homicidal behavior? 10 A. No. 11 Q. Or violent aggressive 12 behavior? 13 A. I'm not aware of any 14 literature to that. 15 Q. Do you know  1 A. Yes. 2 Q. But he's no expert on human 3 behavior, is he? 4 A. That's true, but you asked me 5 who would I go to to see if they knew something. 6 Q. I understand. I'm not saying 7 that you were inaccurate in giving me your 8 answer, I'm just saying that his knowledge is in 9 connection with neurotransmission and the actions 10 of the serotonin system as opposed to whether it 11 might cause homicidal behavior in a particular 12 instance. 13 A. Correct. 14 Q. Qn Did you know that cocaine 15 is a serotonin reuptake inhibitor? 16 A. I don't -- as far as I know, 17 that's not one of its main mechanisms of action. 18 Q. Well, did you know that 19 cocaine acts to inhibit the reuptake of 20 serotonin? 21 A. I was not aware of that 22 specifically. 23 Q. Were you aware that heroin 24 acts in inhibiting the reuptake of serotonin? Page 388 1 A. No. 2 Q. Do you know of any individuals 3 in a prison population who were given Prozac? 4 A. No. 5 Q. It's not unusual to conduct 6 clinical trials on individuals incarcerated in 7 our prison system in the United States, is it? 8 A. It would be unusual at this 9 time. I believe at one time that was common 10 practice, but I don't know of that being done 11 now. Certainly Lilly, when I was there, did not 12 do that as a matter of practice. 13 Q. Why? 14 A. Because we have what we call 15 the Lilly Clinic, which was what we call a Phase 16 1 facility where volunteers came in, I think -- 17 and they were used in these Phase 1 studies. 18 Q. I'm not talking about Phase 1 19 studies, I'm talking about clinical trials that 20 used individuals who were incarcerated in 21 prisons. 22 A. The only times that I've heard 23 discussions about that, using patients in 24 prisons, prisoners as patients, not necessarily Page 389 1 in regard with Lilly, is that there's a consent, 2 informed consent issue and there's the coercion. 3 And as far as I understand, that's the history of 4 why pharmaceutical companies have gotten away 5 from using prisoners as subjects, because of the 6 coercion and potential informed consent conflict. 7 Q. Were any clinical studies done 8 which you're aware employing Prozac to determine 9 whether or not Prozac causes violent aggressive 10 behaviors? 11 A. I'm not aware of any such 12 studies. 13 Q. Were any studies done where 14 the issue was examined whether or not Prozac 15 reduced violent aggressive behavior? 16 A. No, I'm not aware of any. 17 Q. Are depressed individuals 18 individuals that are likely to commit violent 19 aggressive acts? 20 A. Not in my understanding of 21 depression. 22 Q. Are depressed individuals 23 individuals who are likely, according to your 24 information, to commit homicidal acts? Page 390 1 A. Not as a part of their 2 depression. If -- let me qualify it, if they 3 have unipolar major depressive disorder. Now if 4 they have psychotic depression, then I can't say 5 what their behavior might be as a part of their 6 psychosis. 7 Q. Okay. Then tell me what Lilly 8 clinical trials used individuals limited as 9 psychotic depressive individuals to study the 10 effects of Prozac on those individuals. 11 A. I'm sorry, are you asking me 12 if they were included or excluded, I don't know -- 13 Q. Were there any clinical trials 14 that used as exclusively their patient 15 population, individuals who were defined as 16 psychotic depressed individuals? 17 A. No, not that I know of. 18 Q. Was there any consideration 19 given to testing these individuals to determine 20 the effects of Prozac on their particular type of 21 depression? 22 A. Not to my knowledge. 23 Q. Do you know of any statistics 24 that you're aware of -- are you aware of any Page 391 1 statistics that have an analysis of the number of 2 individuals who are psychotically depressed 3 versus unipolar depressed? 4 A. I remember that that question 5 came up about our efficacy, whether we had 6 contamination by patients that should perhaps not 7 have been in the study, that were not unipolar 8 depressed, and it had to do with a question, I 9 believe, from the German government about the 10 efficacy data. And we attempted to, again, 11 create a pure pool of people that we knew had 12 unipolar depressive disorder. There was a very 13 minor activity, and I don't really remember the 14 details, but I remember that issue coming up 15 about just not putting them all in the same 16 analysis or doing a more pure analysis. 17 Q. So there was contemplated at 18 one time doing a pure pool of only people 19 basically who were unipolar depressed? 20 A. Analysis, yes, at some point. 21 (DISCUSSION OFF THE RECORD.) 22 (PLAINTIFFS' EXHIBIT NO. 15 WAS 23 MARKED FOR IDENTIFICATION AND 24 RECEIVED IN EVIDENCE.) Page 392 1 Q. Do you remember yesterday, 2 Doctor Wernicke, when we were talking about the 3 list of concerns that the German government had, 4 and there was a fourteen-item list? I think it's 5 there in front of you. 6 A. Yes. 7 Q. Do you recall that? And do 8 you remember the extended discussion we had 9 concerning differences of opinions when you came 10 to the investigator's opinions on efficacy versus 11 the patient's opinion on efficacy? 12 A. Yes. 13 Q. And how that -- you were of 14 the opinion at that time that the investigator 15 had a better judgment in connection with the 16 efficacy of a product than the patient. 17 A. I don't believe I stated that 18 as an opinion. 19 Q. Is that not your opinion? 20 A. No. 21 Q. What is your opinion 22 concerning whether or not the investigator or the 23 patient is best able to determine whether or not 24 the patient is becoming less depressed? Page 393 1 A. I think the matter is not that 2 simple. I think, as with all clinical data, and 3 I've done this with many different therapies, one 4 always has to look at the totality, one has to 5 gain an overall picture. That's why we use 6 different scales. If it was very clear that 7 there was only one right answer, that's what we 8 would use, nothing more, nothing less. In 9 actuality, patients are different individuals and 10 one has to look at a number of parameters to come 11 up with an overall judgment and then look at that 12 across many patients to make an assessment. 13 Q. All right. So your judgment 14 is is that if a patient's HAMD score is going 15 down, which in just analyzing the HAMD would 16 indicate that patient was becoming less 17 depressed, correct? 18 A. Correct. 19 Q. And the patient's expressions 20 of their impressions was that they were becoming 21 more depressed, you would indeed have a conflict 22 there, would you not? 23 A. Yes, in that patient that 24 would be difficult to resolve. Page 394 1 Q. And is it your testimony that 2 in that situation, you wouldn't necessarily -- 3 you couldn't make a determination based on any 4 one patient, whether the investigator was right 5 or the HAMD scoring system was right or the 6 patient was right in a true assessment of 7 improvement or deterioration of the depressive 8 condition? 9 A. Correct, I wouldn't make an 10 assessment that either one was right or wrong, I 11 would just deal with the data as it is. 12 Q. All right. Now Exhibit 15 is 13 a document that you authored on July 2, 1986, is 14 that correct? 15 A. Yes. 16 Q. It's directed to Mr. J.M. 17 Sartoris, correct? 18 A. Yes. 19 Q. Who is J.M. Sartoris? 20 A. He's an internal auditor, part 21 of the internal auditing group. 22 Q. All right. This concerns a 23 field audit of a particular clinical trial, is 24 that right? Page 395 1 A. Yes. 2 Q. Do you remember that trial? 3 A. I believe this is what we 4 called the low fixed-dose study. 5 Q. All right. You had been asked 6 a question specifically. 7 A. Yes. 8 Q. And I'll quote you the quote. 9 The question pertains to whether or not a patient 10 with prior suicide attempts should have been 11 allowed into the study. As it is true with many 12 issues in the treatment of a complex disease, 13 this is really a judgment call on the 14 investigator. In the protocol we state that 15 patients who are thought to be at a serious 16 suicidal risk -- at a serious risk of suicide at 17 the time not be entered. A history of attempts 18 does not necessarily mean that the patient is 19 thought to be at risk at the time of admission to 20 the study, end quote, correct? 21 A. Yes. 22 Q. Was that generally the MO in 23 determining serious suicidal risk, is that it was 24 generally left to the investigator's Page 396 1 determination? 2 A. Well, they had to make that 3 determination before the patient was entered into 4 the study. 5 Q. And a history of a previous 6 suicide attempt didn't necessarily mean, 7 according to you in July of '86, that that 8 individual was a serious suicidal risk? 9 A. At the time, at the time of 10 admission to the study, that's correct, that was 11 my opinion. 12 Q. Is that still your opinion 13 today? 14 A. Yes. 15 Q. And is that opinion your 16 opinion concerning depressed individuals 17 generally? 18 A. I would say so, yes. 19 Q. That an individual might have 20 been -- might have had a previous suicidal 21 attempt, might have attempted suicide previously, 22 but could at a later date not be a serious 23 suicide risk, is that correct? 24 A. As far as I understand the Page 397 1 question, yes, that was my opinion. 2 Q. And it is your opinion today? 3 A. Yes. 4 Q. You go on to say something 5 that's curious. You say, quote, the suicide 6 factor on the HAMD does not provide an accurate 7 predictor, thus we do not advocate that it be 8 used in place of the investigator's judgment, end 9 quote, correct? 10 A. Yes. 11 Q. Was it your opinion at the 12 time, in July of 1986, that the Hamilton 13 Depression Scale does not -- was not an accurate 14 predictor of suicidality? 15 A. That was my opinion, that that 16 could not be looked at alone, that one had to 17 consider the whole patient. 18 Q. All right. And, therefore, I 19 would assume you would say the same thing for the 20 item three, specific suicide question, on the 21 Hamilton Depression Scale, that it is not an 22 accurate predictor of suicidality. 23 A. Not in and of itself. 24 Q. All right. And you say you Page 398 1 had to consider the patient as a whole, is that 2 right? 3 A. Yes. 4 Q. And, I guess, each patient has 5 to be considered individually, do they not? 6 A. Yes. 7 Q. Concerning whether or not 8 there's a relationship between their depression 9 and their suicidality? 10 A. Yes. 11 Q. You say here that you 12 certainly don't advocate using the Hamilton 13 Depression Scale in place of the investigator's 14 judgment, correct? 15 A. Correct. 16 Q. And txere are you saying that 17 we're going to use the investigator's judgment 18 concerning whether or not that individual patient 19 is suicidal? 20 A. That is the main element of 21 it. The investigator evaluated the patient -- 22 remember there are only four choices on the 23 Hamilton Depression on the suicide question. 24 That doesn't allow for very much information to Page 399 1 be captured. The reason we have investigators 2 that are competent psychiatrists is to make 3 clinical judgments, and we felt that that is 4 where the judgment ought to be made. 5 Q. The judgment on whether or not 6 a patient is a suicidal risk is better made by 7 the investigator than the Hamilton Depression 8 Scale? 9 A. Yes. 10 Q. And whether or not a patient 11 is becoming more or less suicidal is better to be 12 left to the judgment of the investigator than by 13 looking at particular fluctuations within the 14 Hamilton Depression Scale? 15 A. Well, you have to remember 16 what the Hamilton Depression Scale is made for. 17 It's not a diagnostic tool, and that is another 18 reservation why one doesn't even make a diagnosis 19 of depression based on the Hamilton Scale, that's 20 not what it's for, it's designed to track changes 21 over time. 22 Q. Okay. 23 A. And I would feel much more 24 comfortable looking at the changing score than I Page 400 1 would in making a diagnosis based on an initial 2 score, because the test is designed to do 3 different things and qualify and evaluate it and 4 verify it for what they're designed for. 5 Q. Do you think that the HAMD 6 Item 3 is an accurate predictor of changes in 7 suicidality versus that judgment of the 8 investigator? 9 A. That, I'm not sure I could 10 really say which would be better. I think I 11 would have to consider those both. 12 Q. Okay. If an investigator said 13 I think this patient is becoming suicidal, and 14 his HAMD suicidality score wasn't changing, as a 15 physician who would you defer to, Doctor 16 Wernicke? 17 A. The physician, the 18 investigator. 19 Q. And what's the reason for 20 that? 21 A. Because as I explained, the 22 Hamilton -- that item has four choices. He's 23 seen the whole patient. Now I would certainly 24 ask him why, why is that not reflected, that Page 401 1 would be my curiosity. I mean we ought to see 2 it. This has been a widely used scale but I 3 would defer to his clinical judgment. 4 Q. In all candor, in all 5 likelihood, the investigator would tell you, hey, 6 Doctor Wernicke, what you've got there is a very 7 unsophisticated scale, and it's really not 8 designed to pick up what I'm designed to pick up, 9 and that is subtle changes in depression 10 generally and in suicidality specifically -- 11 MR. LORE: I object, that's not a 12 question, and that's -- 13 MR. SMITH: -- correct? I'll put 14 correct on the end of it. 15 A. I don't know -- 16 MR. LORE: It's a statement by 17 counsel, you don't need to respond to that. 18 MR. SMITH: No, that is a question. 19 MR. LORE: What, when you say correct? 20 MR. SMITH: Wouldn't he -- 21 Q. I think I phrased it, wouldn't 22 he in all candor probably respond to you that's 23 what I'm doing, as an investigator, is trying to 24 pick up these subtle changes, and I'm better able Page 402 1 to do that than a twenty-one point scale. 2 MR. LORE: Objection, again, to the 3 form of the question, it calls for him to 4 speculate as to what some investigator may or may 5 not ask him is correct. Doctor, you can go ahead 6 and answer it if you understand it. 7 A. I understand it, and I 8 certainly would -- I think that would be a fairly 9 likely response, but nevertheless I would come 10 back and say yes, but you know, this scale has 11 been used in many, many studies, with thousands 12 of patients. I can't just see -- it would be 13 hard for me to understand how there could be no 14 change on the Hamilton suicide item or any other 15 part and the investigator have a profound 16 impression that there was some change. That 17 would be a real discrepancy that I would have 18 difficulty processing, and I would want -- I 19 would want some explanation beyond well, I know 20 better. That would not really satisfy my 21 curiosity, I suppose. 22 Q. All right. Well, at least in 23 Exhibit 15, in your letter of July 2, 1986, you 24 certainly put in words and in writing the Page 403 1 statement, the suicide factor on the HAMD does 2 not provide an accurate predictor, thus we do not 3 advocate that it be used in place of the 4 investigator's judgment, don't you? 5 A. Yes. 6 Q. All right. Did you ever talk, 7 Doctor Wernicke, to any investigator who 8 administered Prozac clinical trials as to whether 9 or not any reported instances of suicidal 10 ideation occurring during the clinical trials by 11 individuals using Prozac were related to the use 12 of Prozac? 13 A. I don't remember any such 14 conversation. 15 Q. Did you ever talk or inquire 16 of any investigator who was administering Prozac 17 clinical trials and ask them whether or not any 18 particular instance of violent aggressive 19 behavior was in their opinion connected with the 20 use of Prozac? 21 A. I don't remember such a 22 conversation, no. 23 MR. SMITH: Let's take a lunch break. 24 (A LUNCH RECESS WAS TAKEN.) Page 404 1 (PLAINTIFFS' EXHIBIT NO. 16 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. (BY MR. SMITH) Doctor 5 Wernicke, we have just an afternoon left 6 together, so I'm going to try and speed this 7 thing up. And I may paraphrase some things in an 8 attempt to get through this a little quicker, but 9 if I paraphrase something that's inaccurate, 10 would you please stop and let me know? 11 A. Yes. 12 Q. Exhibit No. 16 is a document 13 authored by you and dated January 30, 1986. 14 A. Yes. 15 Q. And it is directed to a number -- 16 well, to Von Keitz in Germany and -- who is that 17 other individual? 18 A. Erl Wood. That's the site, 19 that's to Barbara Von Keitz in Erl Wood. 20 Q. Was Barbara Von Keitz in Erl 21 Wood at that time apparently? 22 A. She may have been at this 23 time. I always thought of her at the German 24 affiliate. Page 405 1 Q. I had, too. 2 A. I don't quite know why that's 3 the way it is, I don't know. 4 Q. Whatever. It was intended, 5 the subject of the letter was intended to be 6 transmitted in relation to the German issue, 7 correct? 8 A. Yes. 9 Q. And to paraphrase, the German 10 affiliates had sent you a number of 11 correspondence inquiring of you to get them some 12 up-to-date information concerning suicide and 13 suicide attempts for the British regulatory 14 authorities, correct? 15 A. I don't know if it was British 16 or German, it might have been German. 17 Q. I mean German. I said 18 British, I meant German. 19 A. Right. They had requested, 20 but we were working on a project together to 21 compile all this data, and in the previous 22 document there was a mention made of accumulating 23 all the worldwide data, and this, as I remember, 24 is what that refers to, and the analysis of all Page 406 1 that data is now coming. 2 Q. Yes. The purpose of my 3 questions is contained in paragraph two of the 4 letter. It says, regarding an update on suicide 5 attempts worldwide, fluoxetine and control, I 6 cannot promise that I can have information 7 compiled by this Thursday. From history, I know 8 that any information put on paper and distributed 9 will be etched in stone, thus I'm not willing to 10 transmit such information until I know it to be 11 correct, end quote. 12 A. Yes. 13 Q. Correct? 14 A. Yes. 15 Q. Then you go ahead and say that 16 you're working on some other projects, right? 17 A. Yes. 18 Q. You say from history your 19 experience has been that it would be -- if it's 20 put on paper, it would be etched in stone. My 21 question is, give me some background of that and 22 why you were hesitant to write down, put on 23 paper, data concerning suicides and suicide 24 attempts? Page 407 1 A. That refers to a general 2 comment of what happens in a large organization. 3 If you write something down and distribute it, 4 that we -- I don't remember exactly -- it has 5 nothing to do with suicides. We had done 6 analyses that were preliminarily distributed to 7 people, and then when we came out with the final 8 analysis, when everything was corrected and 9 verified, those numbers were slightly different, 10 and people got terribly confused and sometimes 11 upset because they had taken that then to do 12 something else with it. So I wanted to be sure, 13 from our standpoint, that what we were releasing 14 was accurate and correct and we didn't have to go 15 back and explain that this was not correct and we 16 had missed a patient and it just leads to a lot 17 of confusion. And we knew this would be used in 18 an important context, as many things were. 19 Q. All right. 20 A. I just wanted to be correct, 21 that's all. 22 (PLAINTIFFS' EXHIBIT NO. 17 WAS 23 MARKED FOR IDENTIFICATION AND 24 RECEIVED IN EVIDENCE.) Page 408 1 Q. Exhibit -- 2 A. 17. 3 Q. -- is a document authored by 4 you dated July 1, 1986, correct? 5 A. Yes. 6 Q. And there you do put some 7 figures down on paper. 8 A. Yes. 9 Q. And this is sent to Doctor 10 Schulze-Solce in Germany, as well as Doctor 11 Weber, Weinstein and Zerbe, correct? 12 A. Yes. 13 Q. And this is what, sir? 14 A. This is a compilation of the 15 suicides and gestures, attempts, all of the 16 events that we were considering at that time that -- 17 what this refers specifically to what was in the 18 safety update that we submitted to the FDA. 19 Q. And this is as of March 31, 20 1986? 21 A. Yes. That was the cut-off 22 date for that safety update. 23 Q. Would this list have included 24 or excluded that list of individuals that were -- Page 409 1 where Doctor Winokur and his group omitted or 2 decided that some of the attempts and gestures 3 were not in fact attempts and gestures that was 4 done back in 1985 that's reflected by this 5 earlier exhibit? 6 A. I'm not sure whether this 7 would have included. Anything that was a suicide 8 or labeled as a suicide attempt or gesture in our 9 DEN data base would be here. What I don't 10 remember is whether the ones that were excluded 11 had never been so coded, and that's why I have to 12 hesitate on that, I just -- I would have to 13 reconstruct what those events were and know the 14 details. I can't be more specific. 15 Q. You can't tell by looking at 16 this -- 17 A. No, I can't. 18 Q. -- whether or not this would 19 be all inclusive or whether or not some of those 20 that Doctor Winokur excluded were not included in 21 this list? 22 A. I can't tell. 23 Q. Now, you list nine suicides as 24 of March 31, 1986, is that right? Page 410 1 A. Yes. 2 Q. And you identify whether or 3 not those patients were on placebo or on 4 fluoxetine. 5 A. Yes. 6 Q. And my calculations was that 7 there was how many on fluoxetine, one, two, 8 three, seven on fluoxetine? 9 A. I see six, because you have 10 three on placebo. 11 Q. Yes, six -- 12 A. Six. 13 Q. Six on fluoxetine and three on 14 placebo. 15 A. Yes. 16 Q. Actual completed suicides. 17 A. Yes. 18 Q. There's no listing of 19 comparator drugs here. 20 A. That's correct. 21 Q. In the deaths, is that right? 22 A. That's correct. 23 Q. Does that mean that nobody 24 committed suicide while on a comparator drug, Page 411 1 such as imipramine, Amytriptoline or something of 2 that nature? 3 A. There would have been no 4 successful suicides on comparators, that's 5 correct, that's what this implies. 6 Q. So an accurate representation 7 would be that in the clinical trials worldwide -- 8 is it worldwide -- yes, it is worldwide, 9 up-to-date, you had had, by March the 31st, 1986, 10 nine individuals who had successfully completed 11 suicides while in the fluoxetine clinical trials, 12 is that right? 13 A. Yes. 14 Q. Of those nine, six were on 15 fluoxetine, three were on placebo, and there were 16 none who were getting other antidepressants that 17 had committed suicide during that period of time, 18 is that right? 19 A. Yes. 20 Q. All right. Next you have 21 listed attempts and -- suicide attempts and 22 gestures that had occurred during the clinical 23 trials, is that correct? 24 A. Yes. Page 412 1 Q. That list -- are all of these 2 individuals, individuals who were in the 3 fluoxetine clinical trials versus -- I mean who 4 were on fluoxetine during the clinical trials 5 versus comparator drug versus placebo? 6 A. I think it would include all 7 of them because we knew we had some on 8 comparators. But I don't know, I can't tell that 9 because that's not listed. 10 Q. Well, it here lists whether or 11 not they had overdosed with fluoxetine or 12 overdosed with -- 13 A. Right. 14 Q. But there's no comparator 15 drugs that were used in overdose, were there? 16 A. I don't remember any. 17 Q. Well, look, I've got it right 18 here in front of you. 19 A. Oh, from what's listed here. 20 No, I don't see any -- I'm sorry, Trazedone, 21 Trazedone, the last one, that could have -- there 22 were Trazedone comparator studies, so that 23 potentially would be one, yes. 24 Q. My first question is, were all Page 413 1 of these patients that were listed under attempts 2 and gestures on Prozac in the clinical trials? 3 A. I don't know that. 4 Q. Why would you not have broken 5 them down? 6 A. Because this was an attempt to 7 make sure we were all looking at the same 8 information. We were finding instances where 9 they were counting people by initials or European 10 number in Europe and we were looking at them by a 11 DEN entry number, and we were trying to reconcile 12 all the patients, make sure we were talking about 13 the right people and to provide them with 14 references to where these were discussed in the 15 safety update. This was not an attempt to be a 16 complete analysis, this is a compilation of here 17 are the cases and this is the reference that 18 talks about that. 19 Q. I'm sorry, I didn't mean to 20 interrupt you, but in discussing the completed 21 suicides, you made a distinction between whether 22 or not the patients were on placebo or 23 fluoxetine, didn't you? 24 A. Yes. Page 414 1 Q. Why wasn't that done in 2 connection with those patients who had attempted 3 suicide? 4 A. I don't remember why we chose 5 to do that. 6 Q. Could it be, Doctor Wernicke, 7 that all of those patients listed who are under 8 attempts and gestures were in fact on Prozac at 9 the time? 10 A. It could be. 11 Q. All right. Now, I see a lot 12 of what we call concomitant medication here, 13 don't we? 14 A. I see in some patients, one 15 listed. 16 Q. Well, I see a lot of 17 comparative -- I mean of concomitant medications 18 listed. I see barbiturates. 19 A. Uh-huh. 20 Q. I see meprobamate. 21 A. Meprobamate, yes. 22 Q. I see -- what is that, cloro -- 23 A. Clorazepam. 24 Q. Clorazepam. Page 415 1 A. Yes. 2 Q. I see clorazepate. 3 A. Yes. 4 Q. I see lorazepam. 5 A. What you see is the drug of 6 which they took an overdose. That does not 7 necessarily mean they were being treated or that 8 these were prescribed at the time. 9 Q. All of those drugs, though, 10 were allowed and used as concomitant medications 11 in the Prozac clinical trials, weren't they? 12 A. I believe so -- well, 13 certainly aspirin was allowed, that's listed as a -- 14 I don't see any that would not be allowed, 15 except, of course, trazedone would not be allowed 16 at the same time. 17 Q. It's another antidepressant. 18 A. As a comparator, but not 19 concomitantly with fluoxetine, that's correct. 20 Paracetamol, I don't remember whether that was 21 specifically allowed. 22 Q. Were you ever comfortable, 23 Doctor Wernicke, that you got a true number of 24 individuals who had attempted suicide and Page 416 1 completed suicide in the Prozac clinical trials? 2 A. Yes, in the trials I was quite 3 comfortable. Of course one can never say for 4 absolutely certain that one has them all. I was 5 quite comfortable that we had them as best as I 6 could tell. 7 (PLAINTIFFS' EXHIBIT NO. 18 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. That's a document also by -- 11 Exhibit 17? 12 A. 18. 13 Q. Is also a document authored by 14 you, directed to Doctor Schulze-Solce, is it not? 15 A. Yes. 16 Q. And that document is also 17 concerning fluoxetine suicides, isn't it? 18 A. Yes. 19 Q. And in that letter, you say in 20 the early days, the criteria for DEN reports were 21 not as strict as they are now, so I'm not sure 22 what was put on the list of suicide attempts 23 necessarily got in the DEN. Likewise, I cannot 24 be sure that what came up on DEN as an attempt Page 417 1 was necessarily considered an event when the 2 first list was made. I realize that this is not 3 very helpful. The only way to answer your 4 question absolutely is to look at each case 5 individually. I have not done this, and I'm not 6 sure that I would -- it would be of any value. 7 The list I've sent, in addition to the cases you 8 already have, represents the most comprehensive 9 compilation from all sources, as far as I can 10 tell, end quote, correct? 11 A. Yes. 12 Q. I take it from what I've just 13 quoted there that there were periods where you 14 were more sure than other periods that all -- 15 everything was being entered into DEN, correct? 16 A. Yes, yes, that's true. 17 Q. And you say the only way to 18 really know is to look at every case report, 19 correct? 20 A. Yes. 21 Q. And that was never done, was 22 it? 23 A. I don't know whether that was 24 done. Page 418 1 Q. Well, it was never done under 2 your direction, was it? 3 A. Well, I wouldn't say that 4 either. What I said here is that I wasn't sure 5 that that would be helpful. This was in July of 6 1986. We did a lot to make sure that we had 7 everything, and certainly as time went by I 8 became much more comfortable that everything had 9 been considered and counted. 10 Q. Did you ever look at each case 11 individually, Doctor Wernicke? 12 A. I don't know whether I looked 13 at every case individually, I don't remember 14 doing that. 15 Q. Well, don't you think you 16 would remember if you had accomplished such a 17 task? 18 A. I did a lot of things in 1986. 19 Q. So did I, but I never looked 20 at each case individually, something that I would 21 consider a time consuming and burdensome job. 22 A. Well, the only ones that would 23 be in question here are the ones that preceded 24 the current DEN criteria. So when I talk about Page 419 1 looking at every case individually, I would only 2 be referring to those very early ones, in any 3 case. So to answer that question, I don't 4 remember whether or not I looked at every one of 5 those. I might have or I might not have, I just 6 don't remember. 7 Q. Would you have written that 8 down had you convinced yourself that you had 9 looked at every case individually and were fully 10 aware of every suicide attempt and suicide 11 gesture that had occurred during the Prozac 12 clinical trials? 13 A. You're asking me if I would 14 have written that down? 15 Q. Yes. 16 A. In the final report that we 17 submitted to the government agencies, I would 18 have given my best assessment of what there was. 19 Q. Did you do that? 20 A. Well, yes, we submitted that 21 in the safety update and into the European 22 regulatory authorities, certainly to Germany. 23 Q. But you don't have a specific 24 recollection of going down -- sitting down and Page 420 1 looking at each case individually? 2 A. That's correct. 3 Q. When was this change in the 4 DEN system made, where it was more likely that 5 you would get captured an event such as this? 6 A. That was before I got this, so 7 I don't know the exact time. But I know there 8 were events that preceded the DEN system. The 9 DEN system is something that was started in a 10 point in time, and events occurred, of course, 11 before then. So from the time that it was fully 12 implemented, it wasn't clear that everything that 13 would now be in DEN was in it from those early 14 days. So -- but I can't say exactly when this 15 change was made. 16 Q. Can you give me an approximate 17 date? 18 A. Well, it was before 1984. By 19 the time I got there, the system was really 20 functioning very efficiently. But beyond that, I 21 can't really say. I believe the system was 22 started sometime in the early '80s, but I don't 23 really recall. 24 Q. How were the pre-DEN system Page 421 1 events collected? 2 A. How were they collected, I'm 3 sorry, is that what you want? 4 Q. Yes. 5 A. What I saw -- what I remember 6 seeing is tabulations of events. How exactly 7 they were collected and processed, I don't really 8 know. 9 Q. Who was doing that collecting 10 and processing, do you know? 11 A. I received it from the 12 clinical research associates. Who actually did 13 the collecting, I'm not sure because it was in 14 the files that we had because that all preceded 15 my coming here. 16 (PLAINTIFFS' EXHIBIT NO. 19 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 Q. Exhibit 19 is a document 20 directed to you from Ms. Von Keitz, is that 21 right? 22 A. Yes. 23 Q. And dated October 3rd, 1986. 24 A. Yes. Page 422 1 Q. Concerning fluoxetine and 2 fluoxetine suicide attempts. 3 A. Yes. 4 Q. And it's talking about a need 5 to get updated figures on suicides and suicide 6 attempts from you, is that right? 7 A. Yes. 8 Q. And to confirm what figures 9 they have contained in this document, correct? 10 A. Correct. 11 Q. She says, quote, the reasons 12 for this urgent request now are the numbers of 13 suicide attempts which have come to our 14 attention. To summarize, the numbers of suicide 15 and suicide attempts of which we're currently 16 aware were -- then she points to the original 17 NDA. I guess that's what was submitted to the 18 Food and Drug Administration originally? 19 A. Yes, correct. 20 Q. And in that there was one 21 completed suicide on fluoxetine and one on 22 placebo. 23 A. Yes. 24 Q. Correct? Page 423 1 A. Yes. 2 Q. As far as attempts were 3 concerned, in the original NDA there were 4 thirteen suicide attempts on fluoxetine and one 5 on Amitriptyline, correct? 6 A. Yes. 7 Q. But that there were additional 8 cases that had arisen as reflected by this since 9 the NDA was filed, correct? 10 A. Yes. 11 Q. Of that, there were on total 12 suicides, seven on fluoxetine, of people who were 13 on fluoxetine, and five on placebo, that's 14 suicide completes, right? 15 A. Four on placebo -- I'm sorry, 16 what did you say? I'm looking at the second 17 page, fluoxetine -- 18 Q. That's where I am. 19 A. Two, four, five, six, and four 20 on placebo. Six on fluoxetine and four on 21 placebo. 22 Q. Well, I'm looking down a 23 little bit further where it says total -- 24 A. Okay. Page 424 1 Q. -- suicides. 2 A. Yes, Okay. 3 Q. Total suicides, fluoxetine 4 seven, placebo five, right? 5 A. Yes. I was looking at the 6 first line, I'm sorry. 7 Q. Am I accurate that that is 8 what that says? 9 A. Yes. 10 Q. All right. Now, suicide 11 attempts is a different figure, isn't it? 12 A. Yes. 13 Q. She reflects here that in 14 connection with suicide attempts, there was 15 forty-seven Prozac treated patients who had 16 attempted suicide, correct? 17 A. Yes. 18 Q. That there were two placebo 19 patients who attempted suicide, that there were 20 two Amitriptyline patients who attempted suicide 21 and one Mianserin? 22 A. Mianserin. 23 Q. Mianserin who had attempted 24 suicide, correct? Page 425 1 A. Yes. 2 Q. Then she goes ahead down there 3 and gives patient populations from the original 4 NDA and the safety update, right? 5 A. Yes. 6 Q. Then she says on the third 7 page, the relation -- of course those numbers 8 don't favor Prozac at all, do they? 9 A. Well, I don't know what the 10 denominator is, I can't make any conclusions 11 about that. 12 Q. Well, the numbers are listed 13 on the bottom of the page, too, aren't they? 14 A. But the duration of treatment 15 isn't. And as we discussed yesterday, that all 16 has to be looked at. 17 Q. By taking into account patient 18 years? 19 A. Yes. 20 Q. Okay. Well then turn the page 21 then. It says the relationship is still not in 22 favor of fluoxetine, even if patient years are 23 considered, end quote, doesn't she? 24 A. That's what she says, yes. Page 426 1 Q. So if you take into account 2 numbers or duration of treatment during patient 3 years, at that time it did not favor Prozac, did 4 it? 5 A. That's her conclusion. 6 Q. Well, it's also Doctor Weber's 7 conclusion apparently, too, isn't it? 8 A. Yes. 9 Q. Did you fire a letter off back 10 to them saying they were wrong? 11 A. I don't remember doing that. 12 Q. Have you seen the German 13 package insert? 14 A. I don't remember seeing that, 15 certainly not recently. I might have reviewed it 16 at this time, but I don't remember it. 17 (PLAINTIFFS' EXHIBIT NO. 20 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Doctor Wernicke, Exhibit No. 21 20 is a translation of the German package insert, 22 an English translation, and had we known that you 23 speak German, we would have probably given you 24 the insert in the original native tongue. But Page 427 1 would you thumb through it generally, and I'm 2 going to ask you some specifics questions only 3 about a few limited parts, so you don't need to 4 memorize all of it. 5 A. Okay. 6 Q. Prozac was approved for use by 7 the citizens of Germany in December, 1989. Does 8 that comport with your recollection 9 approximately? 10 A. Approximately. 11 Q. And the German government 12 required that specific language be contained 13 within the package insert, did it not? 14 A. I'm not sure what their 15 requirements were. I don't know how that 16 language was actually developed, whether there 17 were suggestions, requirements or the affiliate, 18 perhaps, thought that that might be a good idea. 19 I just don't know because I was not involved in 20 the actual manufacturing of the package insert. 21 Q. Okay. Well then are you 22 saying that what's in front of you may have been 23 done voluntarily by the German affiliates? 24 A. I just don't know. Actually Page 428 1 this is not the package insert by the way. 2 Q. Is that the patient 3 prescribing information? 4 A. Yes, that's what it appears to 5 be. 6 Q. All right. Do you know, based 7 on your experience with Germany, that the German 8 government has requirements that the patient 9 prescribing information contain certain language? 10 A. No, I don't know the nature of 11 language that's required, just that there is a 12 requirement for patient information inserted. 13 Q. All right. Turn to page two, 14 would you? It identifies -- has a category there 15 for risk patients, does it not? 16 A. Yes. 17 Q. Under that it says risk of 18 suicide, does it not? 19 A. Yes. 20 Q. And it says Fluctin does not 21 have a general sedative effect on the central 22 nervous system, therefore for his/her own safety, 23 patient must be sufficiently observed until the 24 antidepressant effect of Fluctin sets in. Taking Page 429 1 an additional sedative may be necessary. This 2 also applies in cases of extreme sleep 3 disturbances or excitability, end quote. Did I 4 read that accurately, sir? 5 A. Yes. 6 Q. Do you have any objection to 7 this language in the German package prescribing -- 8 patient prescribing information? 9 A. No, I don't think I do. 10 Q. You think it accurately 11 reflects what your experience has been concerning 12 the Prozac clinical trials? 13 A. No, I don't think I would 14 agree with that either. 15 Q. All right. Would you agree 16 that Fluctin does not have a general sedative 17 effect on the central nervous system? 18 A. That is correct, I would 19 agree. 20 Q. Would you agree that for his 21 or her own safety, the patient must be 22 sufficiently observed until the antidepressant 23 effect of Fluctin sets in? 24 A. I would never limit something Page 430 1 like this, I think every patient needs to be 2 observed, and this is just a small part of that. 3 Q. Do you have objection to that 4 language? 5 A. I don't have objection to 6 that. 7 Q. All right. Do you disagree 8 with that language? 9 A. Only in the sense that I think 10 it implies that once the antidepressant effect 11 sets in, that one does not have to observe the 12 patient carefully anymore, and as a physician I 13 think every patient should be monitored. 14 Q. Okay. Would you agree with me 15 that it's important especially to observe the 16 patient more closely, maybe, during the first few 17 weeks of therapy before the antidepressive effect 18 of Prozac sets in? 19 A. I would agree that that's 20 reasonable. 21 Q. All right. Do you agree that 22 taking an additional sedative may be necessary? 23 A. I would agree with that as a 24 general statement, that for some patients that Page 431 1 may be desirable. 2 Q. All right. Do you agree that 3 this would apply in cases of extreme sleep 4 disturbances? 5 A. Yes, I wouldn't disagree with 6 that. 7 Q. Would you agree that this 8 applies, that is taking of an additional sedative 9 applies in cases of excitability? 10 A. If that were a major feature 11 of that patient's depression, I think that might 12 be appropriate. 13 Q. Do you consider that suicide 14 is a risk of depression? 15 A. Yes. 16 Q. Would you agree that suicidal 17 patients are risk patients in connection with 18 antidepressant treatment? 19 A. They're risk patients because 20 of their disease, not because of the drugs 21 they're taking. 22 Q. I'm not saying that. 23 A. I want to make sure I 24 understand the question. Page 432 1 Q. Then we'll read it back to 2 you. I didn't say that at all. 3 (THE COURT REPORTER READ BACK THE 4 REQUESTED TESTIMONY.) 5 A. Yes, I would agree with that. 6 Q. Do you have any criticism as 7 it's set forth here listing risk of suicide under 8 risk patients? 9 A. No, I don't have any criticism 10 of that. 11 Q. Do you have any criticism with 12 the language that we've quoted being located next 13 to the heading risk of suicide? 14 A. No. 15 Q. Turn with me to page four. I 16 believe that portion of the patient prescribing 17 information is discussing side effects, correct? 18 A. Yes. 19 Q. It's still under the term of 20 side effects, right? 21 A. Yes. 22 Q. Then that last two paragraphs 23 of page four indicate that in addition to the 24 side effects listed above, quote, there are Page 433 1 reports of the following health problems which 2 occur during treatment with Fluctin, which is 3 Prozac, correct? 4 A. Yes. 5 Q. Although Fluctin may not have 6 been the cause. Then in the last two factors, it 7 lists suicidal thoughts and aggressive behavior 8 as side effects that have been reported, correct? 9 A. Not correct. There had been 10 reports, not side effects. To say side effects 11 is to presume causality. We've discussed this 12 before. What it says here, in addition there 13 have been -- there are reports of the following 14 health problems. It does not say that these are 15 side effects of the drug. 16 Q. I wasn't trying to imply 17 anything, the reason I said that -- 18 A. I can only respond to what you 19 said, not what you implied. 20 Q. Well, that language is listed 21 under the side effects section in this patient 22 prescribing information, Doctor. 23 A. Yes. 24 Q. Is it not? Page 434 1 A. Yes, it is. 2 Q. All right. I'm not implying 3 causality -- 4 A. Okay. I just wanted to 5 clarify. 6 Q. -- in using the term side 7 effects. 8 A. I understand. 9 Q. Apparently the German 10 government is not doing that either, because they 11 say in addition there have been the following 12 reports, although Fluctin may not have been the 13 cause. 14 A. Yes, I just wanted to clarify 15 that because of the way the question was stated. 16 Q. And it lists there suicidal 17 thoughts and aggressive behavior, correct? 18 A. Yes. 19 Q. Do you have any problem with 20 it being reported -- 21 A. Absolutely not. 22 Q. -- that suicidal thoughts and 23 aggressive behavior have been reported in 24 connection with use of Prozac, but may or may not Page 435 1 have been the cause? 2 A. I have no problem with that. 3 Q. Do you have any problem with 4 any physician prescribing information that would 5 indicate that in some individuals it has been 6 reported -- there has been reported suicides, 7 suicidal thoughts, suicide attempts and violent 8 aggressive behavior, whether or not these 9 conditions were caused or not caused by Prozac 10 treatment is unknown, period. The patient -- the 11 physician, however, should observe the patient 12 carefully to ensure that these instances don't 13 occur during Prozac therapy, end quote? 14 A. The last sentence, I would not 15 write that way. I don't have trouble with the 16 first part. I think to say that one should do 17 that with Prozac therapy, I think that's in 18 general true, that's good medicine. 19 Q. All right. Would you have any 20 objection to a statement in any prescribing 21 information in connection with Prozac that 22 indicated that there are some who believe that 23 use of Prozac may cause suicidality, suicidal 24 behavior or violent aggressive behavior and the Page 436 1 physician is cautioned in connection with use of 2 Prozac in patients who might be prone to engage 3 in this type of behavior? 4 A. Yes, I would have a problem 5 with that. 6 Q. Based on what? 7 A. That it starts that some 8 people believe. 9 Q. All right. 10 A. And that being that I think 11 package inserts and all information should be 12 based on facts. That doesn't mean there has to 13 be a proof in causal relationship, but it would 14 be like saying -- I'm sure there's still somebody 15 out there that thinks the world is flat, and it's 16 not in the atlases. Things like this need to be 17 based on facts, not on somebody's supposition. 18 Q. Maybe that was a poor thought. 19 How about it has been reported in scientific 20 literature that individuals have become suicidal 21 and violent and aggressive while taking Prozac. 22 Physicians should be cautioned concerning the use 23 of Prozac and individuals of this nature -- in 24 individuals of this nature, end quote? Page 437 1 A. Again, the first sentence is 2 too vague because when you say it has been 3 reported in the scientific literature, that 4 implies true validity. Now one can write a 5 letter to the editor and that's a report in the 6 scientific literature describing a single case. 7 So I think that is just too fuzzy to put into the 8 package insert. 9 Q. All right. When I say package 10 insert, I'm talking about something that will 11 give physicians information concerning Prozac and 12 suicidality and violent aggressive behavior. 13 A. Yes. 14 Q. Do you understand what I'm 15 saying? 16 A. Yes, that is a cornerstone of 17 all information, is the package insert. That 18 goes in the PDR, in fact that's what you see in 19 the PDR is the package insert, and that's what 20 I'm talking about, too. 21 Q. So we're on the same 22 wavelength. 23 A. Yes. 24 Q. Can you, based on your Page 438 1 experience in the clinical trials in Prozac, 2 think of any depressed individuals for whom use 3 of Prozac would be contraindicated? 4 A. Yes. 5 Q. All right. Who would those 6 be? 7 A. Person that has taken it 8 before and has had a severe rash. That may or 9 may not have been the cause and effect, but if 10 there was some other choice, I would rather not 11 challenge that patient again. That's about the 12 only instance that I can think where I would not -- 13 where I would go so far as to say I would 14 consider it a contraindication. 15 Q. If a patient had had previous 16 suicide attempts, would you caution against 17 giving that patient Prozac? 18 A. No. In fact, I think that 19 would be a drug of choice. 20 Q. All right. If a patient who 21 had engaged -- and I'm talking about a depressed 22 patient, you understand? 23 A. Yes. 24 Q. If a depressed patient had Page 439 1 engaged in violent aggressive behavior in the 2 past, would you recommend that they take Prozac? 3 A. Yes. 4 (PLAINTIFFS' EXHIBIT NO. 21 WAS 5 MARKED FOR IDENTIFICATION AND 6 RECEIVED IN EVIDENCE.) 7 Q. Doctor Wernicke, Exhibit 21 is 8 a study synopsis of the Montgomery study that we 9 promised we would get you yesterday. 10 A. Yes, thank you. 11 Q. And if you would like for us 12 to make you an extra copy of this to take with 13 you, we certainty will. 14 A. I see the results, that's 15 fine, thank you. 16 Q. Results weren't that Prozac 17 was beneficial in suicide prophylaxis, was it? 18 A. That's correct. 19 Q. In fact, the results was there 20 was no evidence that fluoxetine affected the 21 success rate in connection with individuals who 22 had experienced suicidal behavior. 23 A. That's correct. 24 Q. There were -- it was a Page 440 1 twenty-four week study, wasn't it? 2 A. Yes. 3 Q. And there were how many 4 patients enrolled? 5 A. Thirty and twenty-seven -- 6 well, those were completers. 7 Q. There were sixty-four 8 fluoxetine patients and fifty-three, is it, 9 placebo patients, or fifty-nine? It's a hundred 10 and seven, fifty-four fluoxetine patients and 11 fifty-three placebo patients. Do you see number 12 of subjects? 13 A. Yes, it's written over here. 14 Q. Is that stamp there irritating 15 to you? 16 A. No, I just didn't see the 17 numbers because they were kind of hidden. That's 18 fine. Fifty-four and fifty-nine, it looks like. 19 Q. No, it's fifty-four and 20 fifty-three, actually. 21 A. Okay. 22 Q. For a total of a hundred and 23 seven patients. 24 A. Yes. Page 441 1 Q. Who entered the study. Of the 2 sixty-four fluoxetine patients who entered the 3 study, it looks like thirty completed, doesn't 4 it? 5 A. Yes. 6 Q. And of the fifty-three placebo 7 patients, it looks like twenty-seven completed. 8 A. That's correct. 9 Q. Got about a fifty percent 10 drop-out rate, don't you? 11 A. Yes, looks that way. 12 Q. And of those Prozac patients 13 that, in fact, the thirty patients that completed 14 the study, only eleven of those made no suicide 15 attempt, is that right? 16 A. That's what it says here. 17 Q. Do I take it that nineteen 18 people who completed the study did in fact make a 19 suicide attempt, is that the way you read that? 20 A. Yes, I would interpret it that 21 way, uh-huh. 22 Q. And that, in fact, eighteen of 23 the placebo patients made suicide attempts? 24 A. Of the completers, yes. Page 442 1 Q. Yes. Then it talks about the 2 MADRS scores. 3 A. Yes. 4 Q. Do you know what that is? 5 A. Yes, it's the Montgomery 6 Asburg Depression Rating Scale. 7 Q. It's sort of the English 8 equivalent to the HAMD, isn't it? 9 A. It's -- in part. It goes a 10 little bit further to -- it's designed to better 11 evaluate non-sedating drugs -- 12 Q. Okay. 13 A. -- is my understanding. It's 14 a refinement, not just an English version. 15 Q. All right. And the MADRS 16 scores given to the patients in that study 17 actually were better for those patients who 18 hadn't had Prozac than those that had. 19 A. That's what it says here, yes. 20 Q. And it's your testimony that 21 the MADRS scores is a better measure of 22 non-sedating antidepressants? 23 A. That's what I have been told. 24 I don't know that I know that myself, that's what Page 443 1 I've heard. 2 Q. Did you hear that while you 3 were employed at Eli Lilly and Company? 4 A. I heard that from Doctor 5 Montgomery, so -- 6 Q. Is that because it's got an M 7 in front there? 8 A. I don't know. He told me 9 that, that this is why this was a good scale, so -- 10 I don't make any causality judgments. 11 Q. Did you ever hear any 12 discussions with the psychiatrists or scientists 13 at Lilly in connection with whether or not they 14 felt the MADRS scale was better at measuring 15 antidepressant effects in non-sedating 16 antidepressants such as Prozac? 17 A. No, I don't remember. There 18 was discussion of whether we should also use this 19 because we were starting to do -- or Lilly was 20 starting to do more and more trials in Europe, 21 and this seemed to be more in vogue in Europe, 22 but not that one was better or not as good, I 23 don't remember those discussions. 24 Q. It lists here the objective of Page 444 1 this study was to compare the prophylactic -- 2 that's preventative, isn't it? 3 A. Yes. 4 Q. To compare the prophylactic 5 effect of fluoxetine and placebo in prevention of 6 suicidal behavior in nondepressed patients 7 suffering from personality disorders with a 8 history of suicidal behavior, correct? 9 A. Correct. 10 Q. I'm a little at a loss, and 11 this thought just hit me. In what instances 12 would you have a nondepressed patient who had a 13 history of suicidal behavior? 14 A. With a personality disorder. 15 Q. Would that be the only 16 instance in which you would see that occur? 17 A. I think there are situations 18 where there's such an overwhelming acute episode, 19 like a severe loss, with patients who might not 20 otherwise qualify as being biologically depressed 21 and might commit suicides. I wouldn't say this 22 is the only one, this is certainly a large group 23 that I know about. And then, of course, 24 psychotic depression, which as we talked about Page 445 1 before is not endogenous depressive disorder, 2 there can be suicides there, too. So that's 3 another large group. Beyond that, I would have 4 to think a little bit more to come up to see if 5 there are other ones that I can think of. 6 Q. Doctor Wernicke, we had not 7 heard, frankly, the term psychotic depression to 8 any extent, hardly at all, in our discussions 9 with Doctors Beasley and Heiligenstein and 10 Wheadon, psychiatrists at Lilly, or with Doctor 11 Dunner, who is a psychiatrist who was a clinical 12 investigator in Seattle. You recall Doctor 13 Dunner, do you not? 14 A. Yes. 15 Q. Is there a DSM-3 or DSM-4 16 diagnosis of psychotic depression? 17 A. I don't know what DSM-4 is. I 18 remember in DSM-3, that is one of the subtypes, 19 as far as I remember. 20 Q. Would that be an Axis 1, Axis 21 2? 22 A. I don't know where it would 23 fall on that scheme. That's fairly technical. 24 Q. All right. What is the Page 446 1 distinguishing characteristics between psychotic 2 depression and your basic unipolar endogenous 3 depression? 4 A. The major distinction is that 5 the treatment is entirely different, and that's 6 why it's important from a medical standpoint. 7 The patient may look identical at that moment and 8 unless one can make a diagnosis, one may in fact 9 be treating the patient with the wrong 10 medication. If it's a psychotic depression, that 11 requires antipsychotics, which is a completely 12 different class of drugs treating a different 13 biological phenomenon than a patient with 14 endogenous depression. 15 Q. Did you answer your question, 16 I didn't mean to cut you off? 17 A. No, that's the main gist of 18 it. And I can give other examples, but that's -- 19 Q. Would Prozac be appropriate 20 for individuals who are suffering from psychotic 21 depression? 22 A. We had no evidence to suggest 23 one way or the other. So by definition, no, 24 because that had not been studied systematically. Page 447 1 Q. So no it would not be 2 appropriate -- 3 A. That's correct. 4 Q. -- to give an individual 5 suffering from psychotic depression Prozac? 6 A. I would say that's correct. 7 Q. Do you know whether or not 8 individuals suffering from psychotic depression 9 is contraindicated in the PDR of Prozac? 10 A. I'm not aware that it's 11 contraindicated. It certainly wasn't then, but I 12 haven't looked at it recently to see if that has 13 changed. 14 Q. What kind of conduct would I 15 be exhibiting if I were suffering from psychotic 16 depression? 17 A. You would have some of the 18 same features of depression, like low mood, 19 perhaps suicidal ideation, lack of energy. But 20 in addition, to achieve the diagnosis of 21 psychosis, you have to have a true thought 22 disorder and not be processing thoughts 23 correctly, have hallucinations, some of the 24 features that make the diagnosis of psychosis, Page 448 1 and that's really related to thought processing 2 and the accuracy of processing of thoughts, not 3 just a slowness of thoughts. 4 Q. What kind of thought? How 5 would individuals like that suffering in 6 psychotic depression, thought practices be 7 jumbled up? 8 A. The -- 9 Q. Or have difficulty being 10 processed, I guess, to use your words. 11 A. They would be likely -- a 12 large group of these patients are more paranoid 13 or paranoid schizophrenic. They are the type of 14 people that hear voices coming from the walls, 15 perceive or are convinced that some force out 16 there is trying to control them. It's usually 17 something fairly specific, the man or the CIA or 18 something is interfering with their thoughts or 19 inserting thoughts in their minds. Those kind of 20 thought processes, in that sense, is that once 21 you examine them you know that that can't be 22 true. If they tell you I know there are people, 23 little creatures coming out of the wall sockets 24 that are going to take me over, that's a good Page 449 1 sign of psychotic thinking. 2 Q. What's the difference in 3 psychotic depression and schizo affective? 4 A. Schizo affective is a milder 5 form that doesn't -- as far as I remember, it 6 doesn't require true hallucinations. These are 7 more the people, perhaps some of the homeless 8 people, that are just sort of on the borderline 9 of mental illness. But schizo affective is 10 generally considered a less severe form of 11 psychosis or on the borderline of psychosis. 12 Q. Okay. And all of these, 13 though, could fit under psychotic depression. In 14 other words, you could have depressive features, 15 you know, like you could have major depression 16 and schizo affective disorder. 17 A. Well schizo affective disorder 18 is sort of on the borderline between affective 19 disorder, which would include depression and 20 schizophrenia, it's not truly totally in either 21 one. A lot of these things in reality are 22 somewhat of a continuum, and there are patients 23 that just fall into a gray zone where you can't 24 really make a definitive diagnosis, and that's Page 450 1 what schizo affective is, they have features of 2 both, and as far as I know it's not really truly 3 understood what the problem is with their 4 biochemistry of their brain. 5 Q. All right. But an individual 6 can be suffering from psychotic depression, 7 correct? 8 A. Yes. 9 Q. And Prozac treatment is not 10 appropriate for that? 11 A. Yes. 12 Q. And within psychotic 13 depression, you'll see individuals who will be 14 having psychotic features, is that right? 15 A. Yes. 16 Q. Such as delusions. 17 A. Hallucinations, delusions, 18 those are different. 19 Q. Hallucinations is something 20 that's not real. 21 A. That's sort of made up. 22 Hallucination is something that that person is 23 convinced they're hearing that in their mind. 24 Q. They're convinced it happened. Page 451 1 A. Right, or they're actually 2 hearing it. When people say they're hearing 3 voices, it's not just that they're thinking might 4 be a voice, their brain hears a voice, 5 presumably. That's what's understood by it. 6 Q. There weren't any clinical 7 trials done with the use of Prozac in individuals 8 with schizo affective disorder? 9 A. Not to my knowledge. 10 Q. The -- in psychotic depression 11 also -- can individuals suffering from psychotic 12 depression be having periods of rage, increased 13 anger or agitation as part of their psychosis? 14 A. I would think so because those 15 can be features of a psychosis. 16 Q. Would Prozac be appropriate 17 for treatment of schizo affective disorder? 18 A. It's not been studied and it's 19 not indicated, and I would say no, because it's 20 not been established to be a therapy. 21 Q. What if you had an individual 22 who is suffering from major depression and had 23 additionally a diagnosis of schizo affective 24 disorder? Page 452 1 A. That would be a therapeutic 2 challenge. 3 Q. All right. Why? 4 A. Because you don't know whether 5 the patient really has both disorders, whether 6 the depression you're seeing is part of this 7 rather vague schizo affective disorder. People 8 can have both. 9 Q. I was going to say individuals 10 can be suffering from major depression and be 11 suffering from schizo affective disorder. 12 A. That's presumably true. There 13 are thought to be overlaps, some patients can 14 have both. 15 Q. That's well known. 16 A. Yes. 17 Q. It's known by the people at 18 Lilly, correct? 19 A. Well, I have always thought it 20 to be true. I can't quote literature to that. 21 Q. You knew it when you were at 22 Lilly. 23 A. I don't remember whether I 24 thought about it in those terms. That never Page 453 1 really came up, as I remember, whether these 2 people had schizo affective disorder and also 3 depression, so -- I mean if I know it, it was 4 coincidental because I don't remember ever 5 thinking about that or talking about that. 6 Q. All right. 7 MR. SMITH: Let's take a break. 8 (A SHORT RECESS WAS TAKEN.) 9 (PLAINTIFFS' EXHIBIT NO. 22 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 Q. Doctor Wernicke, have you had 13 an opportunity to review Exhibit No. 22? 14 A. Yes. 15 Q. That is a letter addressed to 16 you? 17 A. Yes. 18 Q. And do you recall who the 19 author of that letter is? 20 A. No, I do not. 21 Q. Obviously, I'll tell you, we 22 didn't black the author of the letter's name out, 23 that's how we got it. I will tell you that I 24 think probably this individual participated in a Page 454 1 medical opinion leaders forum on psychotropic 2 agents, research development and clinical 3 application on August 26th and 27th, 1985. Do 4 you recall that meeting? 5 A. I recall a series of such 6 meetings, and I concluded that this person must 7 have been at one of those. Not that particular 8 date, but I know that there were a number of 9 these. 10 Q. And this individual is 11 somebody that's knowledgable in psychiatry and 12 was called in by Lilly to give suggestions in 13 connection with the use of Prozac, is that right? 14 A. Yes, yes. 15 Q. Turn with me to page two of 16 what this physician is saying, down at the next 17 to the last paragraph. I'll quote. He says, it 18 will be important to reassure physicians that 19 patients with anxiety and agitation do well with 20 this medication. Do you follow me? 21 A. Yes. 22 Q. They are so used to relying 23 upon the sedating anxiolytic effects of some of 24 the tricyclics as well as the combination Page 455 1 compounds that they may stay away from a drug 2 such as fluoxetine unless you provide very 3 explicit reassurances on this point. Here it may 4 be necessary to address the question of whether 5 the appropriate use of short-term, low-dose 6 benzodiazepine medication may be helpful during 7 the first week or two of treatment. I understand 8 you have virtually no data on this topic, but it 9 may be important to develop this as part of your 10 marketing strategy, end quote, correct? 11 A. Yes. 12 Q. And I believe you testified 13 earlier that there never were any studies done by 14 Lilly to examine the use of low-dose 15 benzodiazepines in connection with Prozac for the 16 first two or three weeks of Prozac treatment. 17 A. Correct, no studies designed 18 specifically to address that issue, yes, that's 19 correct. 20 (PLAINTIFFS' EXHIBIT NO. 23 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 A. Okay, I know this one. 24 Q. Since you wrote it, it's Page 456 1 probably not going to be necessary that you read 2 word for word each of the words in that article, 3 correct? 4 A. Yes. 5 Q. This is an article that you 6 wrote in connection with other individuals at Eli 7 Lilly and Company, correct? 8 A. Yes. 9 Q. And you were employed by Eli 10 Lilly at this time. 11 A. Yes. 12 Q. Now, was this presented at 13 some paper -- as some paper at some meeting? 14 A. Yes, it was. 15 Q. At the American Psyciatric 16 Association? 17 A. No, this was presented at a 18 meeting called the NCDEU. That's an acronym. 19 It's Drug Evaluation Unit. I don't remember what 20 the other ones were. It's a government FDA 21 sponsored symposium for neuropsychopharmacology. 22 Q. And this publication is a 23 psychopharmacology bulletin? 24 A. Yes, and that's where then the Page 457 1 papers are published, yes. 2 Q. It says here, chair, Thomas 3 P. Laughren, M.D., does it not? 4 A. Yes. 5 Q. And we know he is an official 6 with the United States Food and Drug 7 Administration. 8 A. Yes. 9 Q. In fact he was an official 10 with the U.S. Food and Drug Administration that 11 was heavily involved in the review of the Prozac 12 NDA, was he not? 13 A. Yes. 14 Q. You had had communications 15 with Doctor Laughren in connection with that 16 application, had you not? 17 A. Yes. 18 Q. On a number of occasions, 19 didn't you? 20 A. Yes. 21 Q. This paper has to do with 22 what? 23 A. This describes the second 24 fixed-dose study that we did that followed a Page 458 1 twenty, forty, sixty. This was five, twenty, 2 forty, basically, to further our understanding of 3 what the proper dose should be for fluoxetine. 4 Q. All right. And how was it 5 that the original twenty, forty, sixty-dose study 6 was selected as the dosages to be examined? 7 A. The studies before that had 8 used an escalating dose of twenty to eighty. 9 Q. Okay. 10 A. And then it followed that they 11 wanted the studies within that range in a 12 fixed-dose regimen. 13 Q. All right. And that was? 14 A. Twenty, forty, sixty. 15 Q. Twenty, forty, sixty. 16 A. Yes. 17 Q. And then a decision was made 18 to study Prozac at lower dosages, is that right? 19 A. Yes, to confirm and elaborate 20 on that first study. 21 Q. What was the reason to select 22 dosages under twenty milligram to study? 23 A. Well, when one does a 24 dose-response study, it's very nice to have a Page 459 1 no-effect dose so you can kind of start to put 2 boundaries on what's the minimum effective dose, 3 which is what we kind of wanted to determine but 4 really didn't because we saw some effect in some 5 patients, we knew, with the five. So it's a 6 rather broad dose response, so we couldn't 7 determine absolute no-effect dose. But that's 8 the intent of doing what you think is a 9 non-effective dose, but of course you don't know 10 that until you do the study. 11 Q. And it was found that in the 12 low-dose study that five milligram was effective 13 in a number of individuals. 14 A. Correct. 15 Q. In fact was almost as 16 effective as twenty milligrams, correct? 17 A. Almost. 18 Q. And in fact there was no 19 statistical difference in the efficacy of five 20 milligram and twenty milligram. 21 A. On the Hamilton total. As far 22 as I remember, on some of the subscales there 23 was, and I would have to look at all the 24 individual tables to be sure. Page 460 1 Q. Aren't they contained in the 2 paper? 3 A. Yes, but I -- 4 Q. Well, do that. 5 A. -- didn't look at that 6 specifically. I will be glad to do that. For 7 instance, if one looks on Table 3, looking at the 8 weekly analysis for items such as the HAMD 9 retardation, one sees that the twenty milligram 10 there's a statistical significant difference 11 compared to placebo in the third, fourth and 12 fifth week, where it's only two and a third week 13 for the five milligram dose. That's one example, 14 and I believe there are a few others. One has to 15 comb 16 through this fairly carefully to come to the 17 conclusion there's some difference. 18 Q. But can we say that generally 19 speaking, the five milligram and the twenty 20 milligram were -- there was no statistically 21 significant differences in efficacy of these two 22 dosage forms? 23 A. I think that's a little 24 strong. I think there are enough of these types Page 461 1 of individual findings that the five just looked 2 different enough that one would not conclude that 3 they really were equivalent. 4 Q. All right. But almost 5 equivalent. 6 A. Well, how much is almost? 7 There were some differences. 8 Q. And there were some instances 9 where five milligram performed as well as twenty 10 milligram, wasn't there? 11 A. Yes, that's correct. 12 Q. And in fact there were some 13 instances in which five milligram performed 14 better than twenty milligram. 15 A. That's also correct. 16 Q. And some instances in which 17 five milligram performed better than forty 18 milligram even, weren't there? 19 A. Yes. 20 Q. Do you have any scientific 21 explanation for that, Doctor Wernicke? 22 A. Yes. 23 Q. What's that? 24 A. That the ones where the five Page 462 1 actually looked better are exactly what you would 2 predict, and it's on factors like the sleep 3 disturbance. We already knew that drugs like 4 fluoxetine can have an insomnia associated with 5 it, we knew that the rate of insomnia was higher 6 than with placebo. And when one measures sleep 7 disturbance components on the Hamilton, I would 8 not be surprised that those would appear not to 9 respond as well. And that's sort of the basis of 10 what we talked about earlier, the Montgomery 11 Asburg Scale being perhaps more sensitive or 12 perhaps a more appropriate indicator because it 13 doesn't weigh these things so heavily, is my 14 understanding. But that's the basis for that. 15 Q. So are you saying that you're 16 going to have less of a chance of getting a sleep 17 disturbance with five milligram than with twenty? 18 A. Yes, I would say that. 19 Q. And can the same be said with 20 respect to anxiety and nervousness? 21 A. I don't remember that we saw 22 any significant differences, but in general I 23 would have to look up -- as I remember there 24 weren't any differences, but again this is quite Page 463 1 a few years ago. Well, certainly numerically, 2 although we saw -- 3 Q. Well, if you add up anxiety 4 and nervousness at five milligrams as an adverse 5 event, you get twenty-eight percent, won't you? 6 A. Yes. 7 Q. And if you add up anxiety and 8 nervousness in percentage of responses at twenty 9 milligrams, you'll get thirty-three percent, 10 won't you? 11 A. Right, but twenty-seven with 12 forty, and I don't have a good explanation why it 13 looks like it's less with forty. I think some of 14 these things are manifestations of a lot of data 15 and numbers not being exact. Remember these are 16 just reports of a little less than a hundred 17 patients in each group, so one would expect some 18 variability. 19 Q. All right. So, basically, for 20 a number of individuals five milligram would be 21 equally as efficacious, correct? 22 A. Yes. 23 Q. And for a number of 24 individuals five milligram would be less likely Page 464 1 to produce some sides effects than twenty or 2 forty milligrams, correct? 3 A. Yes. 4 Q. Is it correct that the lowest 5 efficacious dose of Prozac has not been 6 established? 7 A. I would say -- 8 Q. Or had not been established at 9 the time of this article? 10 A. It certainly is true for 11 individuals, and that will always be true. As a 12 population, I would say that is still somewhat 13 true, that it has not been established, but 14 further I'm not sure that there is such a thing 15 in reality. Because this is such a flat 16 dose-response curve, I doubt there were ever or 17 can even be a dose that's definitely the lowest 18 effective dose for everybody. That's just not 19 scientifically reasonable. 20 Q. In fact you say on page one 21 eighty-six of your article, under the discussion 22 section, you say from five to forty milligram, 23 the dose-response curve for overall outcome 24 variables, end point and weekly analysis, was Page 465 1 flat. No lower limit for an effective dose of 2 this potent serotonin uptake inhibitor has been 3 demonstrated in moderately depressed outpatients. 4 A. Yes. 5 Q. Correct? 6 A. Correct. 7 Q. The last paragraph of the 8 article says the question of a lower limit for an 9 effective dose of fluoxetine is not answered by 10 this study, nor is the question of whether 11 patients not responsive to low doses would 12 benefit by increases or vice versa, end quote, 13 correct? 14 A. Yes. 15 Q. Looks to me like this study 16 ended up proving or not establishing much in 17 connection with what the proper dose is. 18 A. Well, what it did is just 19 confirm that the twenty milligram dose works. We 20 had two large studies -- 21 Q. You already knew that, didn't 22 you? 23 A. Well, except that it should be 24 confirmed. That's a relatively profound Page 466 1 decision, and one, from a scientific standpoint, 2 to recommend that dose for everyone, it certainly 3 was important to confirm that. 4 Q. Well, Doctor Wernicke, was 5 there a statistician used in connection with this 6 paper? 7 A. Yes. 8 Q. Who was that? 9 A. Bruce Dornseif. 10 Q. Who was Bruce Dornseif? 11 A. He was the statistician 12 involved with this paper and the study. 13 Q. You said that. Is he the 14 senior statistician at Eli Lilly and Company? 15 A. He was the senior statistician 16 assigned to this project. 17 Q. Were there other statisticians 18 under him that worked on the project? 19 A. At this time, I don't know. 20 There were sometimes several, so I can't say for 21 sure whether -- at this time whether there might 22 have been others. 23 Q. Do you recall whether or not 24 Charles Sampson did any statistical work in Page 467 1 connection with this project? 2 A. Not directly. 3 Q. Did he indirectly? 4 A. He was the manager of the 5 statistical group, so he would have been Bruce 6 Dornseif's manager. 7 Q. Okay. From your impression, 8 was the statistical analysis of this five, ten -- 9 or this five, twenty, forty, sixty -- five, 10 twenty, forty study done accurately? 11 A. Yes. 12 Q. With forthright statistical 13 analysis? 14 A. I have no reason to think 15 otherwise. 16 Q. Do you know of any 17 statistician at Lilly that had not done so in 18 connection with collecting and reporting the 19 statistics in connection with any study you've 20 been involved in? 21 A. No. 22 Q. This low-dose study was really 23 your study, wasn't it? 24 A. Well, in a sense, it was. I Page 468 1 saw this one through from beginning to end. 2 Q. It's referred to as the 3 Wernicke study, did you know that, still to this 4 day? 5 A. Is it? Well, that's nice. 6 Q. Well, we'll see. Is your 7 article 23? 8 A. Yes. 9 MR. SMITH: Why don't we mark this 10 next as 24. 11 (PLAINTIFFS' EXHIBIT NO. 24 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Exhibit 24 is a document dated 15 June 11, 1991 and is authored by Doctor Leigh 16 Thompson and directed to Doctor Charles 17 B. Sampson, is it not? 18 A. Yes. 19 Q. Doctor Leigh Thompson is the 20 chief scientific officer at Eli Lilly and 21 Company, is he not? 22 A. At this time, yes. 23 Q. And at the time, June 11, 24 1991, he was the senior vice-president in charge Page 469 1 of the medical division. 2 A. As I remember. 3 Q. Was when you left, wasn't he? 4 A. I believe so, that was his 5 title. 6 Q. He was a senior Lilly 7 official, was he not? 8 A. Yes. 9 Q. And he's directing this 10 correspondence to Doctor Charles Sampson, who is, 11 I believe you said earlier, was head of the 12 statisticians at Eli Lilly and Company. 13 A. He was the immediate manager 14 of people like Bruce Dornseif. 15 Q. Was there a statistician that 16 was -- that occupied a higher position at Eli 17 Lilly and Company than Charles B. Sampson, Ph.D? 18 A. I don't know. 19 Q. Do you think so? 20 A. I don't know of any. If there 21 were, they weren't in his direct line that I knew 22 of. 23 Q. You're aware that now Prozac 24 is produced in a ten milligram solid dosage form, Page 470 1 are you not? 2 A. Yes, I've heard that, yes. 3 Q. The document, read with me. 4 Doctor Thompson tells Doctor Sampson, quote, 5 Charlie, let me ask for help -- you for help in 6 putting together two slides for the Board. And 7 I'll tell you here, the testimony has been 8 undisputed that that's -- the Board that they're 9 speaking of is the Board of Directors of Eli 10 Lilly and Company, okay? 11 A. Yes. 12 Q. I'll continue to quote -- have 13 you seen this document before? 14 A. No. 15 Q. All right. I'll continue to 16 quote. I've got to say something about ten 17 milligram, both in regard to attributes and to 18 the logistics of when we will file in the U.S. 19 International filing is a big, big problem. I 20 don't think we have any ten milligram efficacy 21 data. We do have the Wernicke study of five 22 milligram versus twenty and forty. Some people 23 have massaged those data to make five milligram 24 look not quite as good as twenty milligram. I'm Page 471 1 not sure how that massage was done, but I'd 2 probably need a slide to show whatever it is that 3 makes it look less good. I'd probably also like 4 a slide that shows a more global view of how it 5 works. Do we have a display by week of the HAMD 6 total changes. As I recall, five milligram 7 actually went down a little faster than the 8 other, and ended up about the same. Help me, if 9 you will, on what to show on ten milligram to the 10 Board, period, end quote. Did I read that 11 correctly? 12 A. Yes. 13 Q. When you did this low 14 fixed-dose study, the Wernicke study that's 15 referred to in this exhibit, Doctor Wernicke, 16 were you aware of any massaging of data that 17 occurred? 18 A. That's not a term that I use, 19 that has no concept to me what people or what 20 Doctor Thompson meant by massaging the data. 21 Q. Whatever concept he might use 22 and whatever concept you might use, are you aware 23 of any massaging of data that occurred in that 24 low fixed-dose study? Page 472 1 A. Well, I can't answer because I 2 don't know what massaging data is, it's not a 3 real thing. So there's no such thing as 4 massaging data that I'm aware of now. Now 5 there's falsification of data, there's multiple 6 analysis, there are all kinds of things one does 7 with data, but massaging them is not one of them 8 that I know about. 9 Q. I think you said yesterday you 10 massage people, not data. 11 A. Exactly. 12 Q. Is that right? 13 A. That's what I said. 14 Q. And I think you also said 15 yesterday that massage in connection with the 16 term massaging data could have a negative 17 connotation, correct? 18 A. It could if -- or positive 19 depending on the person and the intents. 20 Q. Tell me how massaging data, in 21 this connection, to make something look less good 22 as is referenced here, would have a positive 23 connotation, Doctor Wernicke? 24 A. In this sense, I would say no. Page 473 1 But to me this would be a negative connotation of 2 massaging. 3 Q. All right. Is this 4 surprising, to see Doctor Thompson talking in 5 this manner in connection with this study? 6 A. If I didn't know Doctor 7 Thompson and some of his flowery language, it 8 would surprise me, but knowing him, I'm not that 9 surprised. 10 Q. Massaging data is not flowery 11 language, is it? 12 A. Well, it's not something -- if 13 he thought there was a really misrepresentation 14 of data, then I would expect that. 15 Q. Well, let's read again what he 16 says and see. You, in fact, have said it appears 17 to have a negative connotation in your mind. 18 A. In some -- depending on the 19 person and the sense that it was used in. 20 Q. He says some people have 21 massaged those data to make five milligram look 22 not quite as good as twenty. 23 A. Yes, that is what he said. 24 Q. All right. Did five milligram Page 474 1 not look as good as twenty in your study, Doctor 2 Wernicke? 3 A. On some parameters, it didn't, 4 that's correct. 5 Q. All right. So was there some 6 data massaged to make it appear that way or 7 altered or changed or reanalyzed? 8 A. Not to my knowledge, and not 9 as a factor in that paper. 10 Q. Was there a lot of statistical 11 analysis that went back and forth between you and 12 Doctor Dornseif in connection with the 13 statistical analysis on your paper and on your 14 study? 15 A. Well, there's a lot involved 16 in it. As you see in the tables, there are many 17 efficacy tables, many multiple analyses. 18 Q. Were there a lot of changes 19 made in that statistical analysis? 20 A. Not that I remember. 21 Q. Were there any changes made in 22 that statistical analysis of which you were 23 aware? 24 A. No. Page 475 1 Q. Do you know of any instances 2 which Mr. Sampson -- or Doctor Sampson, the head 3 of statistics, had any communications with Doctor 4 Dornseif, the statistician that was actually 5 working on this study, in connection with 6 changing or altering data? 7 A. I'm not aware of any such 8 communication. 9 Q. Was Doctor Sampson overseeing 10 Doctor Dornseif in this project? 11 A. As I remember, he was the 12 manager at that time. 13 Q. I understand that, but did you 14 see any memos going from Doctor Sampson or -- to 15 Doctor Dornseif from Doctor Sampson, or vice 16 versa, in connection with a particular 17 statistical method that should be used in 18 analyzing any of this data? 19 A. I do not. 20 Q. Was there any controversy or 21 question going on there? 22 A. Not as far as I knew. Now 23 there was -- there were questions, because as 24 I've pointed out before, on some parameters it Page 476 1 looked like five was better, some looked like 2 twenty or forty was better even. It was not 3 crystal clear that the answer did not fall on the 4 table without any further examination, but I 5 wouldn't say that that's a controversy. 6 Q. All right. Doctor Thompson 7 says, as I recall five milligram actually went 8 down a little faster -- and I'm assuming he's 9 talking about on the HAMD? 10 A. On the HAMD total, yes. 11 Q. Than the others, and ended up 12 about the same, correct? 13 A. That's correct. 14 Q. Was that in fact true? 15 A. Yes, and in fact that's in the 16 paper. One can see that in the graphs. In 17 figure one, that's quite evident. 18 Q. So do you know what it was 19 that was done that was -- to the five milligram 20 data to make five milligram look not quite as 21 good as twenty milligram? 22 MR. LORE: I object, he's already 23 answered that question, Paul. 24 A. In fact, I disagree with that Page 477 1 entire conclusion that it was used, that word 2 massaged or altered or made to look different, I 3 just don't agree with that conclusion. 4 Q. But that's what Doctor 5 Thompson is saying, isn't it? 6 A. That's what this says, yes. 7 Q. Now, why didn't you use ten 8 milligram in this study? 9 A. One had to pick a low dose, 10 and as I've explained before, we were really 11 trying to establish a no-effect dose so we could 12 have a lower boundary. Why didn't we pick seven 13 point four milligrams, I don't know. One has to -- 14 there are only so many things one can do at once. 15 Q. Who made the decision to 16 employ five, twenty and forty as the dosages to 17 study in this study, Doctor Wernicke? 18 A. The initial recommendation or 19 the initial protocol proposal was for five, ten, 20 twenty and forty, as I remember. Then it was 21 decided, and I'm not sure who was involved in 22 that decision, that there really wasn't a need to 23 do a ten, that if we wanted to establish a 24 no-effect dose, five would serve just as well, Page 478 1 and that to do another intermediate dose, since 2 twenty was so safe and effective, would really 3 not be very useful as far as I understood the 4 decision. 5 Q. Is it your testimony here that 6 the purpose of the five, twenty and forty fixed 7 low-dose study was to establish no effect, what 8 no-effect dosage might be? 9 A. That was a secondary. 10 Q. What was the primary? 11 A. The primary was to confirm or 12 to disprove that twenty milligrams was effective. 13 And remember that this was a very profound change 14 in the dosing of antidepressants, traditionally 15 the tricyclics are given in escalating dose. 16 Q. I understand that, and I know 17 what a great selling point it is for Prozac. 18 A. But it's important. 19 Q. That it comes in one dosage, 20 twenty milligram, and that people can start off 21 on it, it's therapeutic, and things of that 22 nature. 23 A. And we felt we needed to slow 24 that -- Page 479 1 Q. But you were studying a dose 2 that was twenty-five percent as powerful, by 3 weight, as twenty, when you were doing the five 4 milligram versus twenty versus forty, correct? 5 A. Correct. 6 Q. All right. Do you know who 7 made the decision to not examine ten milligram? 8 A. No, I do not. 9 Q. Do you know why the decision 10 was made? 11 A. As I just said, the only thing 12 that I heard that it was thought to be a waste of 13 resources, that there was really nothing much to 14 be learned about that. 15 Q. Well, who would make that 16 decision, some scientist? 17 A. There were a number of people. 18 Q. Isn't that a scientific issue? 19 A. Yes. And I would presume and 20 hope there would be a scientist, but I never 21 really -- 22 Q. I'm sorry to disappoint you. 23 Look at that. 24 A. Okay. Page 480 1 (PLAINTIFFS' EXHIBIT NO. 25 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. This is a document authored by 5 Ms. Melissa S. Humbert dated June 5, 1985, isn't 6 it? 7 A. Yes. 8 Q. And it's -- you get a copy of 9 that document, don't you? 10 A. Yes. 11 Q. And it's directed to T. 12 Jeatran? 13 A. Jeatran. 14 Q. Who is that? 15 A. Tom Jeatran. He was 16 responsible for manufacturing in some of the 17 clinical trial materials. 18 Q. And it concerns the fluoxetine 19 fixed low-dose protocol, does it not? 20 A. Yes. 21 Q. And it references a specific 22 Lilly code number for this study, is that right? 23 A. Yes. 24 Q. Is that the study that is Page 481 1 reflected by your paper that we have marked here 2 as an exhibit? 3 A. Yes. 4 Q. It says a decision has been 5 made by Mr. Wood to amend the fluoxetine fixed 6 low-dose protocol. Upon his recommendation we 7 will exclude the ten milligram fluoxetine dosage 8 regimen, correct? 9 A. That's what it says. 10 Q. Mr. Wood that they're 11 referring to is the Chairman of the Board of Eli 12 Lilly Corporation, isn't he? 13 A. Yes. 14 Q. He's not a scientist. 15 A. No. 16 Q. He doesn't have an M.D. or a 17 Ph.D behind his name, does he? 18 A. Correct. 19 Q. Did you originally design the 20 protocol for this study? 21 A. Yes. 22 Q. And you originally included 23 ten milligrams in the study, didn't you? 24 A. That was the plan, yes. Page 482 1 Q. And the Chairman of the Board 2 made a decision not to examine ten milligram, 3 didn't he? 4 A. I don't know that that's what 5 this memo said, but I would submit that Melissa 6 Humbert was not in that meeting. 7 Q. This memo says a decision has 8 been made by Mr. Wood -- 9 A. I see that. 10 Q. -- to amend the fluoxetine 11 fixed low-dose protocol. Upon his recommendation 12 we will exclude the ten milligram fluoxetine 13 dosage regimen, right? 14 A. That's what it says. 15 (DISCUSSION OFF THE RECORD.) 16 Q. Did you talk to Mr. Wood about 17 this decision? 18 A. No. 19 Q. Did you have any conversations 20 with Mr. Wood concerning his decision to amend 21 your protocol? 22 A. No. 23 Q. Have you ever talked to Mr. 24 Wood about anything, Doctor Wernicke? Page 483 1 A. Yes. 2 Q. Have you talked to him about 3 anything in connection with Prozac? 4 A. I gave presentations to groups 5 where he was present. I have not talked to him 6 one on one about that. 7 Q. Have you -- did any of these 8 presentations have to do with the issue made the 9 subject of this memo? 10 A. No, not that I remember. 11 Q. Did you talk to anybody else 12 about this decision of Mr. Wood to amend this 13 protocol to exclude ten milligram dosages? 14 A. I remember hearing about that 15 decision, I believe, from Robert Zerbe, that the 16 decision had been made and that's what we were 17 doing. 18 Q. The decision had already been 19 made before you heard about it? 20 A. Apparently. 21 Q. So you didn't have any input 22 into the decision? 23 A. That's correct. 24 Q. Do you know why the decision Page 484 1 was made? 2 A. Only what I just said before, 3 that the feeling was among the group of people 4 discussing it that there was really not much to 5 be learned. 6 Q. Is Doctor Wood the ultimate 7 authority on what scientifically could and could 8 not be learned in these studies? 9 A. That's not for me to judge. 10 Q. Yes, he's your boss, right? 11 A. He was at that time. 12 Q. Okay. And, in fact, clinical 13 trial materials had already been packed up, 14 hadn't they? 15 A. They were in the process. 16 Q. And they had to be removed 17 from the packets, didn't they, the ten 18 milligrams? 19 A. Some had to be pulled out of 20 that kit, I don't remember exactly what stage 21 they were in. 22 Q. When was this fixed low-dose 23 study completed? 24 A. I don't remember exactly. Page 485 1 Q. Had some patients been given 2 ten milligrams in the study, Doctor Wernicke? 3 A. Not in this study because it 4 hadn't started. 5 Q. Had any patients ever been 6 exposed to ten milligrams of Prozac in a clinical 7 trial? 8 A. In the Lilly Clinic, there 9 were, not depression studies that I know of. I 10 believe in the pharmacology studies there had 11 been patients exposed to ten milligrams, but I 12 don't remember exactly what studies. 13 Q. Well, was their behavior 14 measured? 15 A. They have a panel of tests 16 they do in those Phase 1 studies, but I don't 17 know the details of that in particular. 18 Q. Well, those -- that Phase 1 19 study, Prozac wasn't given to any depressed 20 individuals. 21 A. That's correct, that's what 22 I'm saying. 23 Q. So do you know of any clinical 24 trials that examined the safety or efficacy of Page 486 1 ten milligrams of Prozac in treating individuals 2 with depression? 3 A. I do not. 4 Q. Do you know why Mr. Wood would 5 amend a protocol where clinical trial had been in 6 progress, where materials had been packed up, 7 clinical trial packets had been manufactured to 8 go to the side of this clinical study and then 9 pulled by virtue of this decision? 10 MR. LORE: I object to the form. 11 Paul, you said the clinical trials were in 12 process. 13 Q. Well, they were in the process 14 of conducting the clinical trials by virtue of 15 the fact that they were making the packets up. 16 A. The clinical trial really 17 starts when you admit the first patient. This is 18 preclinical trial. 19 (PLAINTIFFS' EXHIBIT NO. 26 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 Q. Exhibit 29 is a -- 23 MR. LORE: 26. 24 Q. -- 26 is a document that's Page 487 1 been submitted to us by Lilly that concerns the 2 five, ten -- the five, twenty and forty milligram 3 study, is it not? 4 A. Yes. 5 Q. And it talks about 6 correspondence in June, 1985 where the ten 7 milligrams is going to be deleted. 8 A. Yes. 9 Q. So one of these studies was 10 done, I assume, at the University of Utah. 11 A. Yes. 12 Q. Who was the clinical 13 investigator at the University of Utah? 14 A. Gosser. 15 Q. Gosser? 16 A. Gosser. 17 Q. And he had to get permission 18 from the institutional review board at the 19 University of Utah Hospital to amend the protocol 20 to get approval to do this study without the ten 21 milligram dose form, correct? 22 A. Yes, because it was a protocol 23 change. Every protocol change has to go through 24 the IRB. Page 488 1 Q. Five milligram was almost as 2 good as twenty milligram, correct? 3 A. On many parameters. 4 Q. In many parameters it was 5 equally as good, wasn't it? 6 A. Yes. 7 Q. Do you have any scientific 8 judgment, Doctor Wernicke, about whether or not 9 ten milligram might be better than five 10 milligram, and might be just as smacking good as 11 twenty? 12 A. I think that would be very 13 hard to show without doing huge studies. If you 14 ask me about my scientific opinion -- and the 15 reason for that is, if you look at that paper and 16 that study, those differences were rather small, 17 and on some of them there was a statistical 18 significant difference and others not. To truly 19 sort out what their true effect was and what the 20 differences were, would be a huge, huge, study. 21 Q. Well, it's certainly going to 22 be impossible to know if you never run a ten 23 milligram study compared with anything, isn't it? 24 A. Well, that's true. Page 489 1 Q. You had it planned, but it was 2 killed by the Chairman of the Board, wasn't it? 3 A. That's what that memo says. 4 Q. Apparently there was some 5 interest, scientifically, in knowing what the 6 differences in five, ten, twenty and forty would 7 be, but the Chairman of the Board killed it, 8 didn't he? 9 A. That's what that memo says. 10 MR. SMITH: Let's take a quick break. 11 (A SHORT RECESS WAS TAKEN.) 12 * * * * * * * * * * 13 EXAMINATION 14 BY MS. ZETTLER: 15 Q. Doctor Wernicke, my name is 16 Nancy Zettler. We met yesterday morning, I just 17 wanted to reintroduce myself. I also represent 18 the plaintiffs in this action. Can you explain 19 to the jury what an NDA annual report is? 20 A. Yes. It's a report that's 21 submitted, an update that's submitted to the FDA. 22 After the NDA has been filed by law, the statute, 23 we're required -- every company is required to 24 file an annual update. Page 490 1 Q. Okay. What -- is that true 2 for INDs also or is that just true for NDAs? 3 A. Yes, there's an IND annual 4 report also. 5 Q. Okay. What types of 6 information are required to be submitted in an 7 IND annual report? 8 A. Any new studies, results, any 9 findings in the literature. It's fairly vague. 10 Basically anything that's new and considered 11 important to bring the FDA up-to-date with what's 12 happened in the last years. 13 Q. How about NDA annual reports, 14 are there any differences between what is 15 required to be filed with an NDA annual report as 16 opposed to an IND annual report? 17 A. No, not that I can think of. 18 Q. Besides new studies -- results 19 of new studies that were done or completed during 20 the past year and findings in literature, can you 21 think of anything else specifically that must be 22 included? 23 A. Similarly of the spontaneous 24 reports, 1639s. Page 491 1 Q. That's for IND -- or for NDAs, 2 correct? 3 A. For both, we submitted that to 4 both. 5 Q. When you say 1639s for 6 spontaneous adverse event reports were submitted 7 to the IND, were those -- were U.S. spontaneous 8 reports submitted to the IND? 9 A. Yes. 10 Q. Why would that happen? 11 A. Because that's part of what we 12 learned from the experience, that was our 13 safety-gathering mechanism in addition to the 14 clinical trials. 15 Q. I guess what I'm confused 16 about is -- an NDA is filed after an IND, 17 correct? 18 A. Yes. 19 Q. And you only get spontaneous 20 reports, at least in the country where a drug is 21 marketed, after a drug is marketed, correct? 22 A. No. 23 Q. Okay. How would you get a 24 spontaneous report outside a trial, say in the Page 492 1 United States, before it was approved here in the 2 United States? 3 A. An investigator would call up 4 and report an event. If it was a serious event, 5 we would put it in the DEN system in addition to 6 capturing it in the clinical trials. So you 7 could, and in fact we did, have quite a few 8 events that were in the DEN system, slash 1639, 9 in addition to the clinical trials that were 10 pre-NDA even. 11 Q. But those adverse events that 12 occurred during the clinical trials would not be 13 spontaneous adverse events, would they? 14 A. Not spontaneous in the sense 15 of post-marketing. 16 Q. That's what I wanted to clear 17 up. 18 A. If you're making that 19 distinction, you're correct. 20 Q. Okay. We understand that 21 there were adverse events from the clinical 22 trials that were reported to DEN which DEN's 23 primary purpose was to gather and record 24 spontaneous adverse events, though, correct? Page 493 1 A. Spontaneous post-marketing and 2 premarketing, seriously. It really captured more 3 the compassionate use, the extension therapies, 4 which by definition are part of the trial, but 5 may have occurred after that. Their controlled 6 randomized portion of the trial was done and 7 submitted, so there was no good mechanism other 8 than to just send in table after table to pool 9 all that together. 10 Q. Okay. I'm just trying to make 11 sure that the jury understands the distinction 12 between a spontaneous adverse event and an 13 adverse event that occurs during the clinical 14 trial, okay? 15 A. I should correct that, and I 16 used that word too generically. Spontaneous 17 really does, in this sense, mean post-marketing, 18 so that is not quite -- 19 Q. You don't really use the word 20 spontaneous with regards to adverse events that 21 occur during a clinical trial with people who are 22 clinical trial participants, correct? 23 A. That's the correct usage, yes. 24 Q. Okay. So we're talking about Page 494 1 with regards -- let's focus on the IND annual 2 report right now, okay? 3 A. Yes. 4 Q. Besides any studies that may 5 have been done in that past year, findings in the 6 literature, summaries of adverse events that 7 occurred during the clinical trials, correct? 8 A. Yes. 9 Q. What other information would 10 be required to be reported? 11 A. Animal studies, if we had done 12 animal studies in the meantime, tabulation of the 13 number of patients exposed and treated. 14 Q. Anything else? 15 A. Right now I can't think of 16 other specific requirements. 17 Q. How about information from 18 foreign clinical trials? 19 A. I included that in the 20 clinical trials -- I didn't mean that to be 21 restricted to only U.S. 22 Q. Okay. How about any other 23 foreign type of information, what other foreign 24 type of information would be included in the Page 495 1 annual report under the IND? 2 A. I'm not sure. Since the NDA 3 was filed when I got there, I'm not sure whether 4 their submissions to the regulatory agencies 5 would have been filed only to the NDA or both the 6 NDA and IND, and I just don't know whether that 7 was meant to both places. That would have gone 8 to some submissions and maybe both, and of course 9 true spontaneous post-marketing reports, if it 10 was marketed in some countries, that would all go 11 in. 12 Q. For instance if you had a -- 13 if you filed your NDA here but the drug had not 14 been approved here yet but was approved in 15 another country, any spontaneous adverse events 16 that would occur, say, for instance in Belgium, 17 would have been reported to the NDA, correct? 18 A. Yes. And possibly the IND, 19 too. I don't remember, and I was not that 20 closely involved in deciding what went to what 21 channel, this was a rather complex decision. 22 Q. What other foreign information 23 or information that was gathered from outside the 24 United States would be submitted in an NDA annual Page 496 1 report? 2 A. Any activity related to a 3 foreign regulatory body. Amount of material 4 used, that total milligrams, I believe, as I 5 remember that, had been sent out and the estimate 6 of the number of patients exposed, as I remember. 7 Q. Did you ever participate in 8 putting together an annual report submission to 9 the FDA on Prozac? 10 A. Yes. 11 Q. Which annual report, was this 12 fairly regular? 13 A. Once a year. 14 Q. Once a year from the time that 15 you worked there? 16 A. Yes. 17 Q. Do you recall specifically 18 submitting any information regarding the German 19 government, BGA's review of fluoxetine to the FDA 20 in an annual report? 21 A. The only thing specifically I 22 remember is there was two volumes we sent on the 23 responses were included in some submission. 24 Q. Do you recall which submission Page 497 1 that was? 2 A. No, I'm afraid I don't. It 3 would have been that next annual report, but I 4 don't know because it wasn't on the calendar 5 year, so I don't know exactly how those 6 overlapped. 7 Q. It would have been in the 8 annual report after you had submitted it to the 9 BGA? 10 A. After we sent it to the German 11 affiliate. I remember that's the last that I saw 12 of it. It left Indianapolis and then as far as 13 we were concerned it was out and then it was put 14 in the pile of material to be submitted to the 15 FDA. 16 Q. How do you know it was 17 submitted to the FDA if you never saw it after it 18 was sent to the affiliates? 19 A. I didn't see it cross the 20 ocean, I knew at this side it was supposed to be 21 submitted to the FDA, that we included it in that 22 submission. I said I didn't see it, it was -- 23 when we submitted it to Germany. That wasn't the 24 only copy we sent, we kept a copy that we Page 498 1 submitted to the FDA. 2 Q. Are you saying that the German 3 affiliate submitted it to the FDA? 4 A. No. Let me clarify. When we 5 were finished, we sent a copy to the German 6 affiliate. 7 Q. Right. 8 A. This is the responses we 9 prepared in response to these questions. We kept 10 a copy of that, several copies, and submitted one 11 to the FDA. 12 Q. Okay. Did you ever see a 13 final form of the two-volume response? 14 A. Yes. 15 Q. Okay. When did you see that? 16 A. When I was finished doing it. 17 I used to have one on my book shelf because we 18 referred to that data and information. 19 Q. When I say final form, I mean 20 not in German but the form it was submitted to 21 the BGA. 22 A. When I say final form, it's 23 the form that we sent over to the German 24 affiliate. Page 499 1 Q. Okay. And your testimony 2 yesterday, I believe, was besides paginating it 3 and collating it and maybe putting section 4 dividers in, it was essentially the same as when 5 it left Indianapolis, correct? 6 A. No, I didn't testify to that. 7 That's -- I believe the question was what else 8 could have been done to it, and that's -- as I 9 remember, the question was would this be ready to 10 submit in total to the BGA, and well certainly 11 there wasn't a cover letter and pagination, but I 12 don't know whether that was recollated or whether 13 it was all submitted at once, I just don't know 14 what happened and exactly how it happened after 15 it left our office. 16 Q. Other than the responses to 17 the questions posed by the BGA, was there 18 anything else included in that two-volume 19 response to the BGA? 20 A. Not that I remember. 21 Q. Do you recall what the 22 questions were from the BGA? 23 A. One of them was certainly on 24 the number of suicides and deaths. There were Page 500 1 those questions about pooling, the efficacy. 2 There were questions on phospholipidosis, about -- 3 the questions about the diagnosis of the 4 patients, and specifically about the severity of 5 depression, were they endogenous, were they not 6 endogenous patients, what kind of patients were 7 they. Those are the only ones that I remember 8 specifically. 9 (PLAINTIFFS' EXHIBIT NO. 27 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 Q. Do you recognize the exhibit? 13 A. I know it's a cover section of 14 an annual report, I don't remember ever seeing 15 this. 16 Q. You don't -- I'm sorry, could 17 you repeat that? I missed that. 18 A. I recognize that the cover 19 letter refers to an annual report, but I don't 20 specifically remember seeing this particular 21 document. 22 Q. Okay. Well, Doctor Wernicke, 23 after the first -- actually that whole thing has 24 been produced to us as having been the portion of Page 501 1 the -- I believe it's an IND annual report 2 submission, including the German -- or the 3 response to the BGA questions, okay? Now granted 4 I haven't put the entire two volumes in there 5 because, as you know, it's quite thick, so I've 6 selected out a couple of different sections. Do 7 you recognize those sections? 8 A. Yes, I remember -- I remember 9 the twenty-two questions, and I thought there 10 were twenty-two but I didn't want to say that 11 because I wasn't absolutely certain, but in fact 12 that appears to be true. 13 Q. One of the sections that I 14 attached to that exhibit is related to the BGA's 15 question on severe organ damage. If you look at 16 it, I believe it's number sixteen, question 17 sixteen. 18 A. Yes. 19 Q. Okay. The other is in 20 response to the BGA's question regarding suicide. 21 Do you see that? 22 A. That's number eighteen. Yes, 23 uh-huh. 24 Q. Do you recognize those two Page 502 1 sections, Doctor? 2 A. Yes. 3 Q. To your knowledge is there 4 more that encompasses the response to the BGA's 5 question on suicide than what is attached to that 6 exhibit? 7 A. I'm not aware that there's any 8 more to the submission. 9 Q. This looks pretty complete to 10 you, correct? 11 A. As far as I can remember at 12 this time. 13 Q. Do you recall discussing this 14 submission with anybody at the FDA at any time? 15 A. No. 16 Q. What did the BGA mean when 17 they stated that's set out in question sixteen, 18 please explain the significance of lab chemical 19 and enzymatic abnormal deviations and resulting 20 severe organ damage? 21 A. What they meant is, as I 22 remember, that there were laboratory 23 abnormalities in the data set. Remember we had 24 by this time I think well over a thousand Page 503 1 patients, and they had multiple laboratory 2 determinations of multiple parameters. And as in 3 any population, one sees people with abnormal 4 values, and they wanted a fuller explanation of 5 what those were and why they were and what we 6 knew about them. And I believe there was 7 specific mention of liver function tests as I 8 remember, and there might have been others. 9 Q. What are transaminases? 10 A. Those are liver function 11 tests. What they are, they are enzymes that 12 basically as a result of liver damage, they are 13 released. So it's sort of of an indirect -- 14 well, fairly direct measure of liver damage. It 15 doesn't necessarily tell you what the damage is 16 caused by but if say a person has an accident and 17 gets hit or they have a drinking bout, they have 18 liver transaminases go up, so it's a fairly quick 19 way to assess whether there's maybe some kind of 20 liver damage. 21 Q. And the BGA was concerned that 22 they had seen some problems with transaminases 23 with the fluoxetine patients? 24 A. Well, there were some values Page 504 1 that were elevated, and they wanted a fuller 2 explanation of those. 3 Q. Did you provide that 4 explanation to them? 5 A. I would think so. I don't 6 remember what exactly we did, but we talked about 7 them here, so yes. 8 Q. Do you recall the BGA having 9 concerns about fluoxetine or Prozac causing 10 unacceptable damaging effects? 11 A. I did not interpret it as a 12 concern. What -- I think the way I understood it 13 and the way I remember it is this term 14 unacceptable damaging effects is somewhat of a 15 translation issue. What my understanding was is 16 that there was some patients that seemed to have 17 rather elevated liver function tests and some 18 other things, blood urea and nitrogen, that they 19 wanted to have further explored and explained. 20 Q. I'm not talking about severe 21 organ damage, I'm talking about another concern 22 of the BGA's or another question raised by the 23 BGA as to whether or not Prozac had unacceptable 24 damaging effects related to the side effect Page 505 1 profile. Do you recall that? 2 A. Not out of relationship to 3 these laboratory abnormalities, and that's what 4 organ damage -- I'm not sure I'm following. 5 Q. I'm talking about a whole 6 separate issue outside the laboratory values. I 7 think if you look back, I don't recall which 8 exhibit it is, the one that talks about the 9 intent to reject letter I believe? 10 A. Yes, there is mention, I 11 remember there's mention of -- 12 Q. There's mention of 13 unacceptable damaging effects, correct? 14 A. Right. 15 Q. Do you recall what the BGA or 16 can you tell from that exhibit what the BGA meant 17 by unacceptable damaging effects? 18 A. I think, as I remember, they 19 were talking about potential organ damage. 20 Q. So severe organ damage and 21 unacceptable damaging effects in your mind are 22 one and the same? 23 A. That's what I concluded they 24 meant and we explored those things and that was, Page 506 1 as I remember, my interpretation. 2 Q. Do you recall having a 3 conversation with Richard Kapit at the FDA 4 regarding the BGA's questions on severe organ 5 damage and unacceptable damaging effects? 6 A. No. 7 (PLAINTIFFS' EXHIBIT NO. 28 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Exhibit 28 is a copy of a memo 11 written by you, correct? 12 A. Yes. 13 Q. It's dated December 10, '87? 14 A. Yes. 15 Q. It talks about a telephone 16 conversation that you had with Doctors Laughren 17 and Kapit on December 4, '87. Do you see that? 18 A. Yes. 19 Q. And the subject matter of that 20 conversation, at least in part, was Doctor 21 Laughren's and Kapit's question or request to 22 clarify what was meant by certain statements by 23 the BGA, correct? 24 A. It just refers to submission Page 507 1 to regulatory activity, foreign regulatory 2 activity. I'm not sure what country this refers 3 to specifically. 4 Q. Do you recall writing a letter 5 to the FDA answering questions regarding 6 statements made by the BGA? 7 A. Not in specific reference to 8 statements by the BGA. I remember we dealt with 9 some of the same issues, like laboratory 10 abnormalities, but I don't remember that being 11 the outgrowth or the outcome of a BGA 12 correspondence. 13 Q. Do you believe in 1987, 14 December, 1987, that you had a clear 15 understanding of what the BGA meant when they 16 said severe organ damage and unacceptable 17 damaging effects? 18 A. I believe I did. 19 Q. Why didn't you tell the FDA, 20 Doctor? 21 A. Tell them what? 22 Q. Why did you tell the FDA that 23 you didn't know what the BGA meant by severe 24 organ damage and unacceptable damaging effects? Page 508 1 A. If I told them that then I 2 guess that I remember incorrectly what I thought 3 in 1987. Now thinking back, I'm trying to 4 remember what our interpretation of that was. 5 MR. LORE: Do you have a document to 6 show? 7 A. It may be that I didn't. 8 (PLAINTIFFS' EXHIBIT NO. 29 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. Do you recall this letter, 12 Doctor? 13 A. Actually I remember the 14 substance of the letter, but not specifically 15 this particular letter. 16 Q. I know the letter is dated 17 December 4, '87, it's to the Food and Drug 18 Administration and it's authored -- or at least 19 the signature line is tagged Max Talbott, 20 correct? 21 A. Yes. 22 Q. Although somebody else named 23 Sam Robinson signed it for Doctor Talbott, 24 correct? Page 509 1 A. Yes. 2 Q. Do you recall drafting this 3 letter? 4 A. No, I don't. 5 Q. Do you recall submitting this 6 letter to Doctor Allen Weinstein for his review 7 before it went out? 8 A. I don't remember that. 9 Q. Do you agree with what it says 10 in this letter, please explain the significance 11 of lab chemical enzymatic abnormal deviations and 12 resulting severe organ damage, it was never made 13 clear by what the BGA meant by severe organ 14 damage? 15 A. I agree that that's the quote 16 that's given. 17 Q. Do you agree that it was never 18 made clear by the BGA what it meant by severe 19 organ damage? 20 A. I don't remember any specific 21 clarification, and that's why when I answered 22 that before, I was relying on my memory as to 23 what that could possibly mean, and we concluded 24 that it almost certainly meant laboratory, like Page 510 1 liver function damage. 2 Q. In fact on December 4, 1987, 3 you did know that the BGA defined severe organ 4 damages in terms of transaminases, did you not? 5 A. Well, it says it never was 6 made clear what they meant by severe organ 7 damage. 8 Q. Let's see. 9 (PLAINTIFFS' EXHIBIT NO. 30 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 Q. Exhibit 30 is an E-mail from 13 Allen Weinstein to you dated December 4, 1987, 14 correct? 15 A. Yes. 16 Q. That's the same date that the 17 letter to the FDA stating that the BGA never 18 clarified what it meant by severe organ damage -- 19 A. Yes. 20 Q. -- was dated, right? 21 A. Yes. 22 Q. Here it says Joe -- and I'm 23 assuming he means you? 24 A. Yes. Page 511 1 Q. The letter looks fine to me. 2 I have confirmed with Nick Schulze-Solce that 3 the, quote, severe organ damage, end quote, 4 referred to the rare patients with elevated 5 transaminases, correct? 6 A. Transaminases. 7 Q. That's pretty clear that they 8 defined it for you, correct? 9 A. They defined it to Doctor 10 Schulze-Solce at that time. 11 Q. Is there some reason why you 12 didn't trust Doctor Schulze-Solce's 13 communication? 14 A. I don't remember this, but 15 this is after -- this is at the same time that 16 this was. There's no -- I did not know that 17 before, this just came across on December 4th. 18 Q. Doctor Weinstein is approving 19 the letter that was sent to the FDA, correct? 20 A. Yes. 21 Q. And in here he's saying that 22 he knows, according to Nick Schulze-Solce what 23 the BGA meant by severe organ damage, correct? 24 A. That's what he says. Page 512 1 Q. Yet the letter that you sent 2 out to the FDA states that the BGA never defined 3 what severe organ damage meant. 4 A. I did not send that letter. 5 I'm not -- 6 Q. Are they talking about another 7 letter here, Doctor? 8 A. No. But what you're asking or 9 saying is that I sent this letter and I did not. 10 What I'm not clear on is why that letter was not 11 changed. 12 Q. You don't know why the letter 13 wasn't changed? 14 A. That's correct. 15 Q. So you're saying that it 16 should have been changed based on your 17 communication with Doctor Weinstein, correct? 18 A. Well, I would have clarified 19 this in response to this, yes. 20 Q. In fact you talked to Doctor 21 Laughren and Doctor Kapit and told them that the 22 German authorities never defined what they meant 23 by severe organ damage or unacceptable damaging 24 effects, isn't that true? Page 513 1 A. After this -- you're talking 2 about after this? 3 Q. No, on the same day. 4 A. I believe, if my memo says 5 that that may have happened at the same day. 6 This all happened at the same day and I'm not 7 sure of the sequence of events on that day. 8 Q. Did you ever call the FDA back 9 and tell them that you were wrong that the BGA 10 had in fact defined severe organ damage? 11 A. I don't remember doing that. 12 Q. Why not? 13 A. I don't know that it would 14 have made any difference because the conclusion 15 that we had come to was identical to the 16 conclusion that they in fact said was the 17 situation, that it had to do with liver 18 functions. So the fact that they had clarified 19 it is sort of so what, we had come to the correct 20 conclusion. I don't see that there was anything 21 to call about. 22 Q. Do you believe that on this 23 date, December 8, 1987, that the FDA had as much 24 information regarding the safety and efficacy of Page 514 1 fluoxetine as the BGA had? 2 A. From one of these 3 communications from Doctor Weinstein, it appears 4 that they had more. 5 Q. That the FDA had more? 6 A. He said I've also confirmed 7 with him that the BGA has not received our most 8 recent safety update, so the FDA is in possession 9 of considerably more information than the BGA. 10 That's in Doctor Weinstein's E-mail to me of 11 December 4th, Exhibit 30. 12 Q. But your statements to the FDA 13 in the letter that was sent on December 4th 14 insinuate that they not only had a larger amount 15 of information than the BGA but they also had 16 more sophisticated analyses of data, does it not? 17 A. What are you referring to? 18 Q. Exhibit 29. 19 A. But specificly why do you 20 conclude that I said that? 21 Q. In fact the opposite is true, 22 the FDA has reviewed data on more patients using 23 analyses which are much more sophisticated than 24 those submitted it the BGA up to this time, Page 515 1 correct? 2 A. Yes, because we had submitted 3 the safety update and it's those two hundred 4 sixteen volumes that we talked about yesterday, 5 that had already been reviewed by the FDA. There 6 was a comprehensive exhaustive analysis of 7 virtually everything including laboratory 8 abnormalities. 9 Q. Doctor, you have no specific 10 recollection of ever submitting to the FDA the 11 expert report such as Doctor Winokur's that was 12 done on the suicidality issue for the BGA, do 13 you? 14 A. That's correct. 15 Q. Do you recall submitting any 16 other expert reports either gleaned from experts 17 here in the United States or in Germany to the 18 FDA related specifically to the issue of 19 suicidality? 20 A. I do not. 21 Q. So at least in that respect, 22 the FDA didn't have as much information as the 23 BGA, correct? 24 A. In terms -- if one considers Page 516 1 that that is more information, all of the cases 2 that are discussed in there were reported to the 3 FDA. If one considers that that is information 4 above and beyond that then I would concur that 5 that would be correct. But in terms of the data 6 and the information that the FDA had, they had 7 all of those case. 8 Q. Are you satisfied that you 9 individually or Eli Lilly as a company put the 10 FDA on notice regarding the fact that the BGA 11 raised the issue of suicide and the use of 12 fluoxetine back in 1984 and 1985? 13 A. Absolutely. Because if you 14 look at that annual report that's listed right 15 there as one of their questions, those are the 16 BGA's questions to the FDA and our responses, all 17 one would have to do is read that annual report 18 and it would be right there. So I would say say 19 absolutely, yes. 20 Q. Question 18 is with regards to 21 the information that was submitted in the annual 22 report says, the reviewer expressed concern over 23 the number of suicide attempts made by patients 24 treated with fluoxetine, it is suggested that Page 517 1 their attempts are due to a fluoxetine induced 2 deterioration in the clinical condition of 3 patient as protocols for trials excluded patients 4 considered high suicide risks, correct? 5 A. Are you talking about BGA 6 question 18. 7 Q. Yes. 8 A. That's not exactly the way 9 this reads. 10 Q. Okay, how -- 11 A. It says, please provide an 12 in-depth analysis of suicide and suicide attempts 13 (patient by patient, timing, symptomology at 14 trial entry, phase of trial and any other 15 clinically relevant0comments). That's the BGA 16 question that I'm reading from. 17 Q. 0 If you look at the actual -- 18 I'm actually giving you a break here, Doc, it's 19 the beginning of the more is complete question. 20 A. That's what I was looking at, 21 that's why I wasn't following exactly what you 22 were saying. 23 Yes, that is what this says. 24 Q. Okay. Does that question, or Page 518 1 anywhere within this response to the BGA does it 2 talk about the issue of activation or 3 stimulation? 4 A. I would have to look at the 5 other questions, this one does not. 6 Q. I'm talking about specifically 7 with regards to the issue of suicidality which 8 you talked to Mister Smith about at length 9 yesterday and this morning. 10 A. Well, I would have to look at 11 the response again to see whether we deal with 12 that at all, I don't remember that and I haven't 13 read it all over. 14 Q. I'm talking about this section 15 with regards to suicidality. 16 A. I understand, but I don't 17 remember whether we addressed that specific issue 18 because I didn't read all over this response. 19 Q. Go ahead and take a minute and 20 read it. 21 A. I don't see any reference 22 specifically to agitation or events like that in 23 this response. 24 Q. To your knowledge, did you or Page 519 1 anybody at Eli Lilly ever inform the FDA that the 2 suicide issue was a very serious issue to the 3 BGA, in fact it was one of the reasons why they 4 sent the intent to reject letter? 5 A. The questions, all of the 6 questions received from the BGA are here. 7 Q. I understand that, Doctor. My 8 question is, did you personally or did anybody at 9 Eli Lilly ever talk to anybody at the FDA or send 10 them any notification in writing that the BGA 11 considered the suicide incidence with regards to 12 fluoxetine a serious issue and that it was in 13 fact serious enough to be one of the bases of 14 their intent to reject? 15 A. The supposition is that that 16 was any more serious than the others, and the 17 answer directly is that I did not discuss that in 18 isolation with the FDA and I can't speak for 19 other people at Lilly, but what we did send the 20 FDA is all of the concerns of the BGA and how we 21 answered them. 22 Q. Do you have any specific 23 recollection of ever discussing the issue of the 24 BGA raising the suicidality question with anybody Page 520 1 at the FDA? 2 A. I do not. 3 Q. With regards to the issue of 4 severe organ damage, Doctor, if you in fact had 5 submitted the responses to the BGA questions in 6 the early 1985 submission of the annual report, 7 why didn't you simply refer Doctor Laughren and 8 Doctor Kapit to that submission since you had it 9 available to you on your shelf as you testified 10 earlier? 11 A. Because we had a lot more data 12 by then. The data that was in the safety update 13 in 1987 was much, much more comprehensive than 14 what was in the '85 submission to the BGA on that 15 issue. 16 Q. But section sixteen of that 17 submission discusses the issue of severe organ 18 damage fairly thoroughly, does it not? 19 A. Not as thoroughly as the 20 safety update. 21 Q. It gives you enough 22 information to understand what the BGA is talking 23 about when they asked you to explain the 24 possibility of severe organ damage? Page 521 1 A. Yes, but that was superseded 2 by a much larger data set that the FDA already 3 had. 4 Q. To your knowledge, did that 5 much larger data set change the question posed by 6 the BGA regarding severe organ damage? Because 7 my understanding, Doctor, is the only thing 8 they're asking here is what the BGA meant when 9 they referred to severe organ damage, correct? 10 A. Yes, that's what I would glean 11 from it. 12 Q. It's a simple question, you 13 could have answered it by just pointing them to 14 the 1984 submission to the BGA, correct? 15 A. But they -- I will have to 16 read their notes of that conversation. 17 Yes, from my memo on Exhibit 18 28 of December 10th, I talk about them wanting 19 clarification as to what they meant. However I 20 would not feel it appropriate to say well, go to 21 that submission, the annual report 1985 or 22 whenever it was, when there was much more data 23 available to them at this time, that just doesn't 24 seem appropriate. Page 522 1 Q. It wasn't appropriate for you 2 to tell them that the BGA never clarified their 3 definition of severe organ damage either, was it, 4 Doctor? 5 A. That was my understanding at 6 that point, which obviously Doctor Weinstein then 7 at the same day or sometime clarified. 8 Q. Which you never called and 9 clarified with the FDA, correct? 10 A. No, because as I remember this 11 was the same conclusion that we had come to. 12 Q. In fact the FDA relied on your 13 representations that the BGA never defined either 14 the term unacceptable damaging effects or severe 15 organ damage, and in fact never pursued either of 16 these issues further based on their reliance on 17 your representations, isn't that true? 18 A. I wouldn't say that that's 19 true because what we concluded were the issues in 20 fact were pursued and were exhaustively 21 investigated. 22 Q. Take a look at Exhibit Number 23 31, please. 24 (PLAINTIFFS' EXHIBIT NO. 31 WAS Page 523 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 A. Okay. 4 Q. This Exhibit 31 is a memo 5 written by Doctor Kapit, correct? 6 A. Yes. 7 Q. It's dated December 8, 1987, 8 correct? 9 A. Yes. 10 Q. It states, on December 4, 11 1987, a letter from Dr. M. W. Talbott relayed Dr. 12 J. Wernicke's response to a teleconference with. 13 Dr. T. Laughren and this reviewer regarding 14 comments made by the German regulatory authority 15 (the BGA) on the safety of Prozac, correct? 16 A. Yes. 17 Q. The letter asserted that the 18 German authorities never defined or documented 19 the phrases severe organ damage or unacceptable 20 damaging effects which were used in their 21 communications to the company, correct? 22 A. Yes. 23 Q. The letter denies that any 24 such organ damage has ever occurred in fluoxetine Page 524 1 treated patients, correct? 2 A. It says that, yes. 3 Q. The company asserts that all 4 information made available to the BGA has been 5 made available to the FDA, and to their 6 knowledge, the FDA has used more sophisticated 7 analyses in reviewing the data, correct? 8 A. Yes. 9 Q. Conclusion: The BGA comments 10 do not appear to reflect clinical events since no 11 such events have been reported to the FDA, and 12 according to the company, we have received all 13 information submitted to the BGA, correct? 14 A. Correct. 15 Q. Recommendation: The comments 16 by the BGA should not affect FDA's conclusion 17 that NDA 18-936 -- which is the NDA for Prozac, 18 correct? 19 A. Yes. 20 Q. Is approvable, correct? 21 A. Yes. 22 Q. Why is it that the BGA saw 23 problems with laboratory levels? 24 MR. LORE: It's been asked and Page 525 1 answered already. 2 MS. ZETTLER: No, it hasn't. 3 MR. LORE: The doctor has been asked, 4 Nancy, but go ahead. 5 MS. ZETTLER: First of all, let me 6 finish my question, Steve. 7 MR. LORE: You finished your question. 8 MS. ZETTLER: No, I didn't. 9 MR. LORE: Well, go ahead and finish 10 your it. 11 MS. ZETTLER: You cut me off in the 12 middle of my question. 13 Q. (BY MS. ZETTLER) Why is it 14 that the BGA saw problems with laboratory values 15 related to liver and the FDA's never seen an 16 adverse event related to severe organ damage or 17 any organ damage whatsoever according to this? 18 A. The premise that you started 19 with is that the BGA saw abnormalities of 20 laboratory values, is that correct, and that is 21 true, those are in every data base. But that's 22 different than adverse events related to organ 23 damage, which is also true. So there's really no 24 discrepancy at all. Page 526 1 Q. Were the abnormalities 2 reported as adverse events to the FDA? 3 A. If -- usually they came out 4 through an analysis of the laboratory data. That 5 does not mean there could not have been some 6 1639s related or reporting liver function 7 abnormality, there were some, but I don't know 8 how many, and that may have been a report, an 9 adverse event report of an observation of an 10 abnormal laboratory value. 11 Q. BGA comments do not appear to 12 reflect clinical events since no such events have 13 been reported to the FDA. They're relying on 14 your company to report such events to them, 15 correct? 16 A. Yes, and we reported all 17 adverse events. 18 Q. Do you know that for an 19 absolute fact now, Doctor? 20 A. I know that as far as I was 21 involved that everything that we gathered was 22 reported. Now whether it actually went in an 23 envelope on a truck out the door, I was not there 24 to see it and I was not there to see the FDA Page 527 1 receive it. 2 Q. So you know that the adverse 3 events came in to Lilly, correct? 4 A. Yes. 5 Q. You know that they were 6 entered into the DEN system, correct? 7 A. Yes. 8 Q. But you can't say for certain 9 whether or not they actually made it to the FDA, 10 can you? 11 A. That's correct. 12 MS. ZETTLER: Nothing further. 13 MR. SMITH: No further questions. 14 (THE WITNESS WAS EXCUSED.) Page 528 1 COMMONWEALTH OF KENTUCKY ) 2 : ss COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 DR. JOE WERNICKE 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 7TH DAY OF 19 SEPTEMBER, 1994. 20 MY COMMISSION EXPIRES MARCH 10, 1994. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 529 1 E R R A T A S H E E T 2 3 STATE OF ) : SS 4 COUNTY OF ) 5 6 I, DR. JOE WERNICKE, THE UNDERSIGNED 7 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 8 OF MY DEPOSITION AND WITH THE CHANGES NOTED 9 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 10 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 11 THE 25TH AND 26TH OF AUGUST, 1984 AT THE TIME AND 12 PLACE STATED THEREIN. 13 PAGE NO. LINE NO. CHANGE REASON Page 530 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. JOE WERNICKE 10 SWORN TO AND SUBSCRIBED BEFORE ME THIS 11 _____ DAY OF __________, 1994. 12 _____________________________ NOTARY PUBLIC, STATE OF 13 AT LARGE Page 531 1 2 3 4 5 6 7 8 9 10 Page 532 1 DIRECT EXAMINATIONBY MR. SMITH:.....14 2 EXAMINATIONBY MS. ZETTLER:.........491 3 COMMONWEALTH.........530 4 (QUESTION CERTIFIED.)........74 5 PLAINTIFFS' EXHIBIT NO. 1..........118 6 PLAINTIFFS' EXHIBIT NO. 2..........128 7 PLAINTIFFS' EXHIBIT NO. 3..........130 8 PLAINTIFFS' EXHIBIT NO. 4..........214 9 PLAINTIFFS' EXHIBIT NO. 5..........236 10 PLAINTIFFS' EXHIBIT NO. 6..........252 11 PLAINTIFFS' EXHIBIT NO. 7..........260 12 PLAINTIFFS' EXHIBIT NO. 8..........264 13 PLAINTIFFS' EXHIBIT NO. 9..........274 14 PLAINTIFFS' EXHIBIT NO. 10.........296 15 PLAINTIFFS' EXHIBIT NO. 11.........310 16 PLAINTIFFS' EXHIBIT NO. 12.........343 17 PLAINTIFFS' EXHIBIT NO. 13.........345 18 PLAINTIFFS' EXHIBIT NO. 14.........379 19 PLAINTIFFS' EXHIBIT NO. 15.........393 20 PLAINTIFFS' EXHIBIT NO. 16.........406 21 PLAINTIFFS' EXHIBIT NO. 17.........409 22 PLAINTIFFS' EXHIBIT NO. 18.........418 23 PLAINTIFFS' EXHIBIT NO. 19.........423 24 PLAINTIFFS' EXHIBIT NO. 20.........428 Page 533 1 PLAINTIFFS' EXHIBIT NO. 21.........441 2 PLAINTIFFS' EXHIBIT NO. 22.........455 3 PLAINTIFFS' EXHIBIT NO. 23.........457 4 PLAINTIFFS' EXHIBIT NO. 24.........470 5 PLAINTIFFS' EXHIBIT NO. 25.........482 6 PLAINTIFFS' EXHIBIT NO. 26.........488 7 PLAINTIFFS' EXHIBIT NO. 27.........502 8 PLAINTIFFS' EXHIBIT NO. 28.........508 9 PLAINTIFFS' EXHIBIT NO. 29.........510 10 PLAINTIFFS' EXHIBIT NO. 30.........512 11 (PLAINTIFFS' EXHIBIT NO. 31........524 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 Page 534