1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT 2 DIVISION ONE (1) 3 *-*-*-*-* 4 JOYCE FENTRESS, ET AL. PLAINTIFFS 5 6 VS. DEPOSITION FOR PLAINTIFFS 7 8 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 9 10 11 *-*-*-*-* 12 13 14 DEPONENT: ALLAN J. WEINSTEIN, MD 15 16 DATE: JUNE 29 AND 30, 1994 17 18 REPORTER: MARY KATHLEEN NOLD 19 20 *-*-*-*-* 21 22 KENTUCKIANA REPORTERS 730 WEST MAIN STREET, SUITE 250 23 LOUISVILLE, KENTUCKY 40202 (502) 589-2273 24 1 1 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 2 INDIANAPOLIS DIVISION 3 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 4 Litigation ) 5 *-*-*-*-* 6 NO. 91-02496-A 7 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 8 V. ) DALLAS COUNTY, TEXAS ) 9 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 10 *-*-*-*-* 11 NO. 92-14775-E 12 RICHARD HAROLD CROSSETT, JR., ) IN THE 13 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT,) COURT OF 14 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 15 JOCQUETTA ANN CROSSETT, DECEASED ) ) 16 V. ) DALLAS COUNTY, ) TEXAS 17 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 18 PSYCHIATRIC COMPANY, INC. ) D/B/A HCA WILLOW PARK ) 101st JUDICIAL 19 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D ) 20 *-*-*-*-* 21 22 23 24 2 1 NO. A-921,405-C 2 MARIA GUADALUPE REVES ) IN THE INDIVIDUALLY AND AS NEXT ) DISTRICT COURT 3 FRIEND OF GRANT JULIAN REVES ) OF A MINOR CHILD, AND ON BEHALF ) 4 OF THE ESTATE OF CHRISTIAN ) MARIE REVES, DECEASED ) 5 ) V. ) ORANGE COUNTY, 6 ) TEXAS ELI LILLY & COMPANY, DISTA ) 7 PRODUCTS COMPANY, RAVIKUMAR ) KANNEGANTI, M.D., HOSPITAL ) 8 CORPORATION OF AMERICA, A ) TENNESSEE CORPORATION, HEALTH ) 9 SERVICES ACQUISITION CORP., ) A DELAWARE CORPORATION, ) 10 HCA PSYCHIATRIC COMPANY, A ) DELAWARE CORPORATION, TEXAS ) 11 PSYCHIATRIC CO., INC., A/K/A ) AND/OR D/B/A HCA BEAUMONT ) 12 NEUROLOGICAL HOSPITAL, AND HCA) HEALTH SERVICES OF TEXAS, INC.) 128TH JUDICIAL 13 A/K/A AND/OR BEAUMONT ) DISTRICT NEUROLOGICAL HOSPITAL ) 14 *-*-*-*-* 15 16 17 18 19 20 21 22 23 24 3 1 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS COUNTY DEPARTMENT - LAW DIVISION 2 RENATO DI SILVESTRO, Individually) 3 and as Special Administrator of ) the Estate of JOHN DI SILVESTRO, ) 4 Deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91-l-7881 ) 7 ROBERT L. NELSON, et al., ) ) 8 Defendants, ) ) 9 GEORGE MELNICK, M.D., and PETER ) FINK, M.D. ) 10 ) RESPONDENTS IN DISCOVERY.) 11 *-*-*-*-* 12 SUPERIOR COURT OF THE STATE OF CALIFORNIA 13 FOR THE COUNTY OF LOS ANGELES 14 DR. MARIUS SAINES, etc., et al., ) Case No.: ) SC 008331 15 ) Plaintiffs, ) 16 ) vs. ) 17 ) ELI LILLY & COMPANY, a corporation;) 18 DISTA PRODUCTS COMPANY, a Division ) of Eli Lilly & Company; and DOBS 1-) 19 100, Inclusive, ) ) 20 Defendants. ) ___________________________________) 21 *-*-*-*-* 22 23 24 4 1 NO. 93-8792-D 2 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF 3 INDIVIDUALLY AND AS SURVIVORS ) AND STATUTORY BENEFICIARIES ) 4 OF MAY YUN KUNG, DECEASED ) ) 5 VS. ) DALLAS, COUNTY ) TEXAS 6 ELI LILLY AND COMPANY, DISTA ) PRODUCTS COMPANY, AND MONIQUE ) 7 KUNKLE, PH.D. ) 8 *-*-*-*-* 9 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS CIVIL COURT DEPARTMENT 10 EUGENE HUSLIG, AS ADMINISTRATOR ) 11 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 12 HUSLIG, DECEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 13 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 14 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 15 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 16 ) 94 C 192 PLAINTIFFS, ) 17 ) COURT NO. 7 VS. ) CHAPTER 60 18 ) MARY L. BILLINGSLEY, EXECUTOR OF ) 19 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 20 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 21 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 22 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 23 ) DEFENDANTS. ) 24 5 1 CAUSE NO. 93-04911-A 2 LINDA JILL WELCH, CARLINDA WELCH REX, CONNAN ROSS WELCH 3 AND CHAD MICHAEL WELCH, INDIVIDUALLY AND AS SURVIVORS 4 AND STATUTORY BENEFICIARIES OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 5 V. 6 ELI LILLY AND COMPANY, DISTA 7 PRODUCTS COMPANY, NOE NEAVES, M.D., AND MINITH-MEIER 8 CLINIC, P.A. DEFENDANTS 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 6 1 I N D E X 2 WITNESS: ALLAN J. WEINSTEIN, MD 3 DIRECT EXAMINATION BY MR. SMITH................ 10 4 CROSS-EXAMINATION BY MS. ZETTLER.............. 492 5 WITNESS EXCUSED............................... 500 6 WEINSTEIN EXHIBIT NO. 1....................... 103 WEINSTEIN EXHIBIT NO. 2....................... 109 7 WEINSTEIN EXHIBIT NO. 3....................... 126 WEINSTEIN EXHIBIT NO. 4....................... 133 8 WEINSTEIN EXHIBIT NO. 5....................... 136 WEINSTEIN EXHIBIT NO. 6....................... 141 9 WEINSTEIN EXHIBIT NO. 7....................... 155 WEINSTEIN EXHIBIT NO. 8....................... 176 10 WEINSTEIN EXHIBIT NO. 9....................... 190 WEINSTEIN EXHIBIT NO. 9A...................... 321 11 WEINSTEIN EXHIBIT NO. 10...................... 196 WEINSTEIN EXHIBIT NO. 11...................... 204 12 WEINSTEIN EXHIBIT NO. 12...................... 230 WEINSTEIN EXHIBIT NO. 13...................... 238 13 WEINSTEIN EXHIBIT NO. 14...................... 248 WEINSTEIN EXHIBIT NO. 15...................... 255 14 WEINSTEIN EXHIBIT NO. 16...................... 286 WEINSTEIN EXHIBIT NO. 17...................... 296 15 WEINSTEIN EXHIBIT NO. 18...................... 314 WEINSTEIN EXHIBIT NO. 19...................... 321 16 WEINSTEIN EXHIBIT NO. 20...................... 335 WEINSTEIN EXHIBIT NO. 21...................... 352 17 WEINSTEIN EXHIBIT NO. 22...................... 360 WEINSTEIN EXHIBIT NO. 23...................... 373 18 WEINSTEIN EXHIBIT NO. 24...................... 403 WEINSTEIN EXHIBIT NO. 25...................... 410 19 WEINSTEIN EXHIBIT NO. 26...................... 417 WEINSTEIN EXHIBIT NO. 27...................... 433 20 WEINSTEIN EXHIBIT NO. 28...................... 443 WEINSTEIN EXHIBIT NO. 29...................... 447 21 WEINSTEIN EXHIBIT NO. 30...................... 459 WEINSTEIN EXHIBIT NO. 31...................... 468 22 WEINSTEIN EXHIBIT NO. 32...................... 471 WEINSTEIN EXHIBIT NO. 33...................... 474 23 WEINSTEIN EXHIBIT NO. 34...................... 479 WEINSTEIN EXHIBIT NO. 35...................... 484 24 7 1 THE FOLLOWING DEPOSITION 2 OF ALLAN J. WEINSTEIN, MD WAS TAKEN AT THE OFFICES 3 OF BAKER & DANIELS, 300 NORTH MERIDIAN STREET, 4 SUITE 270, INDIANAPOLIS, INDIANA, 46204, ON JUNE 5 29 AND 30, 1994; SAID DEPOSITION TAKEN PURSUANT TO 6 NOTICE IN ACCORDANCE WITH THE RULES OF CIVIL 7 PROCEDURE. 8 *-*-*-*-* 9 A P P E A R A N C E S 10 11 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 12 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 13 14 15 PAUL SMITH COUNSEL FOR PLAINTIFFS 16 745 CAMPBELL CENTER 2 8115 NORTH CENTRAL EXPRESSWAY 17 DALLAS, TEXAS 75206 18 19 JOE FREEMAN LAWRENCE J. MEYERS 20 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 21 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 22 ATLANTA, GEORGIA 30308-3243 23 24 8 1 APPEARANCES (CONTINUED) 2 MARY HUFF ELI LILLY AND COMPANY 3 LILLY CORPORATE CENTER INDIANAPOLIS, INDIANA 46285 4 5 6 BEATRICE M. SMITH COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 7 FRIEND & ASSOCIATES LLP 1301 MCKINNEY, #2900 8 HOUSTON, TEXAS 77010 9 10 BARTON BROWN COUNSEL FOR DOCTOR BILLINGSLEY 11 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 10111 WEST 8TH STREET 12 PO BOX 12290 OVERLAND PARK, KANSAS 66282 13 14 15 ROBERT L. HARRIS COUNSEL FOR NOE NEAVES, MD 16 SIFFOLD & ANDERSON, LLP 6300 NATIONS BANK PLAZA 17 901 MAIN STREET DALLAS, TEXAS 75202 18 19 20 21 22 23 24 9 1 MR. FREEMAN: Let me just 2 state at this time a little brief stipulation. 3 This is the deposition of ALLAN J. WEINSTEIN taken 4 on behalf of the plaintiffs for purposes of 5 discovery and use at the trial on any of the cases 6 heretofore recited. The deposition of Doctor 7 Weinstein is taken by agreement of counsel and by 8 notice in the offices of Baker and Daniel in 9 Indianapolis. 10 Objection will be made at 11 this time as to any leading questions that Doctor 12 Weinstein's own counsel may put to him or any 13 objection that any lawyer may have to the 14 witness's response to the questions propounded. 15 All other objections will be reserved until the 16 time of court hearing. 17 *-*-*-*-* 18 ALLAN J. WEINSTEIN, MD, 19 called by Plaintiffs, after having been first duly 20 sworn, was examined and deposed as follows: 21 22 DIRECT EXAMINATION 23 BY MR. SMITH: 24 Q Would you state your 10 1 name, please, sir? 2 A Allan Weinstein. 3 Q How old a man are you, 4 sir? 5 A Fifty-three. 6 Q Where do you live? 7 A xxxxxxxxxxxxxxxxxx 8 xxxxxxxxxxxxxxx. 9 Q Does anybody live with 10 you there, Doctor Weinstein? 11 A My wife. 12 Q Is your wife employed 13 outside the home? 14 A No. 15 Q How long have you lived 16 at the xxxxxxxxxxxxxxx address? 17 A xxxxxxxxxxxxx. 18 Q You are currently 19 employed by Eli Lilly and Company? 20 A Yes. 21 Q What is your title with 22 Eli Lilly and Company? 23 A Vice President of Lilly 24 Research Laboratories. 11 1 Q Are you vice president of 2 any particular area? 3 A The primary 4 responsibility is medical activities outside the 5 United States. 6 Q Give me, Doctor 7 Weinstein, your educational background, starting 8 with when and where you graduated from high 9 school, please, sir. 10 A I graduated from a school 11 called Phillips Academy, which is also known as 12 Andover, in 1958. I graduated from Yale 13 University in 1962, undergraduate school. I 14 graduated from Columbia University with an MD in 15 1966. 16 Q Where were you from 17 originally? 18 A Boston. 19 Q Do you still have 20 relatives in the Boston area? 21 A Yes. 22 Q What was your degree from 23 Yale in? 24 A History. 12 1 Q Then you went to Columbia 2 and got your MD degree? 3 A Yes. 4 Q That's a curious 5 background with a degree in history from Yale, 6 then going to medical school. Did you have to 7 take some leveling courses or anything of that 8 nature? 9 A No. 10 Q Did you take any basic 11 science courses at Yale? 12 A Yes. 13 Q Can you give me the 14 approximate number of the hours? 15 A There were four courses, 16 the courses required to get into medical school. 17 Q After you completed 18 medical school, what type of postgraduate training 19 did you have as a physician? 20 A I had an internship and 21 residency in internal medicine, and then a 22 fellowship in infectious disease. 23 Q Did you take your 24 internship and residency at the same location? 13 1 A No. 2 Q Where did you take your 3 internship? 4 A New England Medical 5 Center in Boston. 6 Q Was that a one-year 7 general rotating internship? 8 A It was a one-year 9 internal medicine internship. 10 Q Then where did you do 11 your residency? 12 A The hospital's name has 13 changed, but at the time it was called the Peter 14 Bent Brigham Hospital in Boston. 15 Q Can you give that to me 16 again? 17 A Peter, as in Peter, Bent, 18 B-E-N-T, Brigham, B-R-I-G-H-A-M. 19 Q How long did that 20 residency last? 21 A One year. 22 Q And you say that was in 23 internal medicine also? 24 A Yes. 14 1 Q And then you did a 2 fellowship in infectious diseases? 3 A Infectious diseases. 4 Q Where? 5 A Massachusetts General 6 Hospital. 7 Q How long did that last? 8 A Three years. 9 Q Any other postgraduate 10 training, Doctor Weinstein? 11 A There were two years in 12 the midst of that in which I was at the National 13 Institutes of Health, which was military service 14 but also training. 15 Q What years were you at 16 NIMH? 17 A It was NIH. 1968 to 18 1970. 19 Q Would it be accurate to 20 state then, Doctor, that after you graduated from 21 Columbia in 1966, you did one year of internship 22 at the New England Medical Center, through 1967, 23 and then did you go to the NIH or did you do your 24 one-year internal medicine residency? 15 1 A Residency. 2 Q Then the National 3 Institute of Health, completed that in 1970, and 4 then went for your fellowship in infectious 5 diseases, and completed that in what, 1973? 6 A 1973. 7 Q Did you take any 8 undergraduate courses in psychology? 9 A No. 10 Q Did you take any 11 psychiatry courses in securing your MD degree from 12 Columbia? 13 A Yes; whatever the 14 required ones were. 15 Q Nothing past the basic 16 required psychiatry courses? 17 A No. 18 Q Do you recall how many 19 courses that consisted of, Doctor? 20 A No, I don't recall. 21 Q Was there any focus on 22 psychiatry during your internship at New England 23 Medical Center, or your residency at Peter Bent 24 Brigham Hospital? 16 1 A No. 2 Q Was there any focus on 3 psychiatry at the National Institute of Health? 4 A No. 5 Q What did you do while you 6 were at the National Institute of Health? 7 A Cancer research. 8 Q Specifically what? 9 A Specifically looking for 10 the possibility that certain viruses are 11 responsible for producing certain forms of cancer. 12 Q At Massachusetts General, 13 where you did your fellowship, was there any 14 emphasis or curricula involving psychiatry? 15 A No. 16 Q During your training, did 17 you treat any individuals with psychiatric 18 disorders? 19 A I was involved in the 20 care of people who had psychiatric disorders. 21 Q Were you responsible for 22 the psychiatric care of those individuals? 23 A No. 24 Q It would be in the 17 1 general internal medicine care that your expertise 2 would be used? 3 A Or infectious disease. 4 Q Then after you completed 5 your fellowship, what was your next job? 6 A I was Assistant Professor 7 of Medicine and Assistant Professor of 8 Microbiology at the University of Pennsylvania, 9 School of Medicine. 10 Q How long were you at the 11 University of Pennsylvania, School of Medicine? 12 A Two years. 13 Q Why did you join the 14 faculty there at the medical school at the 15 University of Pennsylvania? 16 A I'm not sure I understand 17 the question. 18 Q Were you interested in 19 pursuing academic endeavors as a career? 20 A Yes, I entered academic 21 medicine and this was my first position. 22 Q What was your next 23 position then? 24 A In 1975, I went to the 18 1 Cleveland Clinic in Cleveland, Ohio, where I was 2 in the Department of Infectious Disease, and was 3 also on the faculty of the medical school in 4 Cleveland, which is called Case Western Reserve 5 University. 6 Q Was the Cleveland Clinic 7 a private for-profit clinic? 8 A No, it's -- the Cleveland 9 Clinic is very similar to the Mayo Clinic. It's 10 called the Cleveland Clinic Foundation and there's 11 an international referral center. 12 Q Were you paid a salary in 13 your position there, sir? 14 A Yes. 15 Q And you did, or at least 16 your work or your remuneration didn't come as a 17 result of billing patients for your services? 18 A No. 19 Q Did the clinic bill the 20 patients for their services? 21 A Yes. 22 Q How long were you at the 23 Cleveland Clinic? 24 A Eight years. 19 1 Q Until 1983? 2 A Yes. 3 Q While you were on the 4 faculty of Case Western University Medical School, 5 what was your position? 6 A Eventually it was 7 Clinical Associate Professor of Medicine. 8 Q And what was your 9 specialty? 10 A Infectious disease. 11 Q Were you on the faculty 12 at Case Western the entire time you were at the 13 Cleveland Clinic? 14 A Now, I think I joined the 15 faculty shortly after I joined the Cleveland 16 Clinic, within a year or two. 17 Q Did you teach 18 continuously during your time there? 19 A Yes. 20 Q Why did you join the 21 Cleveland Clinic as opposed to continuing in your 22 academic career with the medical school? 23 A The Cleveland Clinic is 24 an academic institution in which I was able to 20 1 teach and do research and see patients, and it was 2 merely a continuation of my academic career. 3 Q Give me a breakdown as to 4 the percentages of time you were spending treating 5 patients as opposed to research and teaching while 6 you were at the Cleveland Clinic? 7 A I'd spend about 8 twenty-five percent of my time doing research, 9 approximately twenty-five percent teaching, and 10 fifty percent in patient care. 11 Q What was that research 12 involving? 13 A It had to do with 14 antibiotics. 15 Q And you were, I guess, 16 still teaching in the area of infectious diseases? 17 A No. 18 Q What were you teaching 19 in? 20 A I'm sorry, can you repeat 21 the question? 22 Q I assume you were still 23 teaching in the area of infectious diseases at 24 Case Western University? 21 1 A Yes. 2 Q Did any of the patient 3 care that you delivered at the Cleveland Clinic 4 involve psychiatric care? 5 A I was involved with 6 patients who had psychiatric disorders. 7 Q Were you a physician 8 administering psychiatric care to those patients? 9 A No. 10 Q Did the Cleveland Clinic 11 have staff psychiatrists that would do that 12 function, sir? 13 A Yes. 14 Q Why did you leave the 15 Cleveland Clinic? 16 A I chose to make a career 17 change and joined Eli Lilly. 18 Q Why did you choose to 19 make a career change? 20 A After having been in 21 academic medicine for ten years, I looked at other 22 possible places where I could use my skills and 23 decided that it might be a challenge to work in 24 the pharmaceutical industry. 22 1 Q Did you seek any other 2 options other than looking into the pharmaceutical 3 industry? 4 A Yes. 5 Q What were those? 6 A Other academic positions. 7 Q With other medical 8 schools? 9 A Yes. 10 Q Full time? 11 A Yes. 12 Q Did you ever consider 13 private patient care? 14 A No. 15 Q Why? 16 A Because it did not 17 interest me; I was more interested in using my 18 medical skills in other ways. 19 Q In research or academics? 20 A In either one or both of 21 those. 22 Q What did you consider to 23 be the challenge presented by Eli Lilly and 24 Company? 23 1 A I believe the challenge 2 in the pharmaceutical industry was the development 3 of new drugs for diseases for which there was not, 4 at the time, adequate therapy. 5 Q And did you interview 6 with or seek positions with other pharmaceutical 7 firms in addition to Eli Lilly and Company? 8 A Yes. 9 Q Which ones, sir? 10 A The primary one was 11 Squibb, which is now called Bristol-Meyers/Squibb. 12 Q Have you done any private 13 practice at all? 14 A No. 15 Q Who did you interview 16 with in 1983 with Eli Lilly? 17 A I cannot remember all of 18 the people; one of the people was Doctor Ian 19 Shedden, I believe with Doctor Leigh Thompson, but 20 I can't remember the others. 21 Q Doctor Weinstein, my name 22 is Paul Smith, we've been introduced. I represent 23 a number of individuals whose loved ones have been 24 affected by the drug Prozac, fluoxetine 24 1 hydrochloride, manufactured by Eli Lilly and 2 Company, and I filed suit on their behalf against 3 Eli Lilly and Company. You understand that? 4 A Yes. 5 Q We have taken several 6 depositions in this case, but let me caution you 7 that this deposition can and will be used as 8 evidence in the trial of this case. Therefore, if 9 you have any questions concerning my questions to 10 you, if you are uncertain or unclear concerning 11 what I'm asking you, would you please let me know? 12 A Yes. 13 Q That way we'll have a 14 clear record and be communicating on the same 15 line, all right? 16 A All right. 17 Q Have you had an 18 opportunity to discuss with Lilly's attorneys what 19 a deposition is and what we're doing here today? 20 A Yes, sir. 21 Q Have you reviewed any 22 documents, Doctor in preparation for this 23 deposition? 24 A No. 25 1 Q When were you first 2 contacted by Lilly lawyers, either in-house or 3 private lawyers, in connection with giving your 4 deposition? 5 A Many months ago. 6 Q Can you give me a better 7 estimate other than many months, sir? 8 A At least six months ago. 9 Q And who were you 10 contacted by at that time? 11 A I believe Mary Huff. 12 Q And have you had any 13 other contacts by any other individuals other than 14 Ms. Huff? 15 A What kind of 16 individuals? 17 Q Concerning giving your 18 deposition. In other words -- 19 A Lilly individuals? 20 Q Either Lilly or somebody 21 from Mr. Freeman's firm, Mr. Myers, any other 22 lawyers representing Lilly. 23 A I've met with these 24 gentlemen. 26 1 Q When did you meet with 2 them? 3 A Over the course of the 4 last three to four months. 5 Q How long would these 6 meetings have occurred? 7 A How long did the meetings 8 last? 9 Q Yes. 10 A Approximately four to six 11 hours. 12 Q And on how many 13 occasions? 14 A I believe two or three. 15 Q And at any of those 16 meetings, were you shown any documents in 17 connection with this case? 18 A No. 19 Q In the course of your 20 employment at Lilly, as I understand it, you 21 received instructions from the Legal Department to 22 periodically turn over those portions of your file 23 dealing with Prozac to the Legal Department for 24 copying and storage; did you understand that? 27 1 A Yes. 2 Q Did you do that? 3 A Yes. 4 Q And would you do that on 5 a quarterly basis, or do you recall how that was 6 done? 7 A I don't recall. It was 8 done by my secretary, who responded to the 9 requests when they were made. 10 Q Did you review documents 11 that were going to be submitted to the Legal 12 Department prior to their being submitted to the 13 Legal Department? 14 A No. 15 Q You physically weren't 16 involved in that transfer of documents at all? 17 A No. 18 Q Do you currently maintain 19 a Prozac file? 20 A I don't know. My 21 secretary may, but I'm not aware of maintaining a 22 Prozac file. 23 Q Well, if you want to look 24 at documents in connection with fluoxetine 28 1 hydrochloride, how do you go about doing it, sir? 2 A I have not had the 3 opportunity to look at documents related to 4 fluoxetine hydrochloride specifically in the last 5 year. 6 Q Well, before that, then. 7 A Before that, I had files. 8 Q All right, and how would 9 those files be divided, into correspondence and 10 particular subjects, or would you just have one 11 large Prozac file? 12 A They were divided by 13 country. 14 Q By virtue of your job 15 duties requiring you to oversee various foreign 16 countries, is that correct? 17 A Yes. 18 Q Is that how you always 19 maintained your files? 20 A Generally. 21 Q Did you have separate 22 correspondence files for correspondence coming in 23 on Prozac, or would the correspondence from 24 England go in the English Prozac file and the 29 1 correspondence from, say, Taiwan go in the Taiwan 2 file? 3 A I would presume that the 4 correspondence from England would go in the 5 England file and the correspondence from Taiwan 6 would go in the Taiwan file. I did not 7 specifically get involved in the filing. 8 Q We have been produced 9 portions of your file; I assume we've been 10 produced all your file except those portions that 11 were not required to be produced by various court 12 orders, but we've seen E-mail and things of that 13 nature, interoffice communications directed to you 14 and sent by you in connection with Prozac. Were 15 those communications kept separately or were they 16 divided in some manner? 17 A I really don't know. 18 Q You'd just ask your 19 secretary for something and she would bring it to 20 you? 21 A That's correct. 22 Q Have you had the same 23 secretary for a number of years? 24 A No. 30 1 Q All right, tell me what 2 your first job duty was with Eli Lilly and 3 Company. 4 A It was called Director of 5 International Medical Affairs. 6 Q And how long did you hold 7 that position, sir? 8 A A year or two; I can't 9 recall the specific. 10 Q Who was your immediate 11 supervisor? 12 A The initial immediate 13 supervisor was a man named Doctor Charles 14 Christensen. 15 Q Did you say Karos, 16 K-A-R-O-S? 17 A Charles Christensen, and 18 he was subsequently replaced, when he retired, by 19 Doctor Thomas Emmick. 20 Q E-M-M-O-C? 21 A E-M-M-I-C-K. 22 Q What was Doctor 23 Christensen's position when he was your 24 supervisor? 31 1 A Vice President of Lilly 2 Research Laboratories. 3 Q And Doctor Emmick? 4 A Same, vice president. 5 Q As Director of 6 International Medical Affairs, did you have 7 physicians under your supervision here in 8 Indianapolis? 9 A Not initially. 10 Q And how long was it 11 before you had physicians under your supervision 12 here in Indianapolis? 13 A It was not at all when I 14 had that title. 15 Q My question was when you 16 were the Director of International Medical 17 Affairs. 18 A No. 19 Q What were your job duties 20 as Director of International Medical Affairs? 21 A My primary job duty was 22 to stimulate the performance of first rate 23 clinical research in countries other than the 24 United States. 32 1 Q How did you go about 2 doing that? 3 A I worked with Lilly 4 employees, Lilly medical employees around the 5 world, particularly in Europe, and with outside 6 experts to interest them in doing clinical 7 research on some of our new compounds. 8 Q Did you have any 9 criticism, after you had an opportunity to 10 evaluate it, of the performance of the clinical 11 research outside of the United States that had 12 been done for Lilly up to the time that you joined 13 Lilly? 14 A No. 15 Q The reason I ask is you 16 said you wanted to stimulate performance of first 17 rate clinical research outside the US, and I'm 18 wondering if that implies that there was something 19 that you found deficient in the quality of outside 20 US clinical research at Lilly? 21 A No, the purpose of my job 22 was to institute research outside the United 23 States, which had not been done very much at all 24 by Lilly previously, and since Lilly research was 33 1 first rate in the US, my job was to stimulate the 2 same type of research in other countries. 3 Q Had there been, as far as 4 you know, some type of corporate decision that 5 there should be more research done outside the 6 United States than had been done up to the time 7 you joined the division? 8 A I can't answer that, I 9 don't know. 10 Q Well, were you expanding 11 the amount of research that was going to be done 12 outside the United States? 13 A That was my goal. 14 Q Therefore, after you 15 started, there was more outside US clinical 16 research than there had been prior to your coming 17 to Lilly? 18 A Yes. 19 Q When you took the job, 20 were you told that this was something that Lilly 21 wanted to be done? 22 A I was told that Lilly was 23 interested in expanding its clinical research 24 activity. 34 1 Q Were you told why? 2 A No. 3 Q And were you told 4 specifically that Lilly was interested in 5 expanding its clinical research facilities into 6 foreign countries? 7 A Yes. 8 Q As opposed to expanding 9 its research facilities within the United States? 10 A It was not a question of 11 as opposed to; Lilly had very adequate and well 12 run clinical research activities in the United 13 States. This was not outside the United States as 14 opposed to inside the United States, it was an 15 expansion of what already existed here. 16 Q But it was in addition to 17 what had existed outside the United States 18 previous to your joining Lilly? 19 A Yes. 20 Q And I'm wondering, were 21 you given any reason as to why there was an 22 interest in increasing the amount of OUS research? 23 A I was not specifically 24 given a reason. 35 1 Q Did you come to some 2 understanding generally concerning that reason? 3 A My understanding is, and 4 I in fact promulgated this idea, was that it was 5 important to study new compounds in populations 6 other than those in the United States, where the 7 practice of medicine may be different than that in 8 the United States, where patient characteristics 9 and disease diagnosis may be different than that 10 in the United States, and as a global company it 11 makes good sense medically to do such studies. 12 Q Is this particularly 13 appropriate in the infectious disease area? 14 A It is particularly 15 appropriate in all areas. 16 Q All right. But 17 infectious disease had been your background? 18 A It's not specific to 19 infectious disease. There are certain infectious 20 diseases that exist in certain countries that are 21 very different than those here, but that's not 22 what the field of infectious disease is generally 23 about. 24 Q Why don't you enlighten 36 1 me, then, concerning that? 2 A Concerning what? 3 Q When you say that's 4 generally not what the field of infectious disease 5 is about. 6 A The specialty of 7 infectious disease in this country was a 8 consultative specialty that takes care of 9 individuals with other primary diseases who have 10 become infected due to a variety of things; in 11 most cases, those are individuals with cancer, 12 individuals who have been immunocompromised, whose 13 defenses are down, individuals who have had major 14 surgery, and in fact the only thing that's really 15 changed over the course of the last twenty years 16 with regard to that is that now we have HIV 17 infection and those are people with a primary 18 infectious disease. But in the main, what is 19 taken care of by infectious disease people are 20 what one might call the complications of other 21 disease or other therapy. 22 Q How did you go about 23 doing this; did you start hiring outside 24 investigators or establishing clinical trials 37 1 outside the United States? 2 A I spent a year or two 3 beginning to learn more about who the experts were 4 in given fields, particularly in western Europe, 5 who our own staff were, and began to work with the 6 people running research in Indianapolis at Lilly 7 to promote the idea that we could begin to do more 8 and more work outside the United States. 9 Q Who was primarily 10 responsible for this research within the United 11 States at that time? 12 A I believe it was Doctor 13 Leigh Thompson. 14 Q Did he give you guidance 15 on the types of research that was going on within 16 the United States? 17 A I was aware of that as a 18 member of the management team of the medical 19 group, I was fully familiar with what was going 20 on. 21 Q Had you done any clinical 22 trial work prior to joining Lilly? 23 A Yes. 24 Q When and where? 38 1 A I had done clinical trial 2 work both at the University of Pennsylvania, and 3 more so at the Cleveland Clinic. 4 Q What clinical trial work 5 had you done at the University of Pennsylvania? 6 A It was clinical trial 7 work looking at antibiotics. 8 Q Were you conducting a 9 clinical trial or were you administering 10 particular antibiotics to particular individuals 11 and recording their response to that antibiotic? 12 A Yes. 13 Q Or placebo -- 14 A Placebos are not used in 15 antibiotic trials. 16 Q You use comparators? 17 A Always. 18 Q Any other work at the 19 University of Pennsylvania? 20 A What type of work? 21 Q Clinical trial work. 22 A No, it was all related to 23 antibiotics. 24 Q Who was the manufacturer 39 1 of the antibiotic under investigation? 2 A I believe it was Merck. 3 Q Were you a principal 4 investigator or were you a physician that was just 5 seeing patients in connection with that trial? 6 A I was a co-investigator, 7 I was not a principal investigator. 8 Q Were you responsible to 9 reporting to the company the results of the 10 clinical trial? 11 A I was one of the 12 physicians performing the clinical trial and had 13 the obligations of a co-investigator. 14 Q Were you filling out case 15 report forms? 16 A Yes. 17 Q And data concerning 18 patient response to the drug? 19 A Yes. 20 Q Did you do anything in 21 connection with interpreting those results, or did 22 you just report your findings to the company? 23 A Reported the findings. 24 Q Any other clinical trial 40 1 work done at the University of Pennsylvania 2 Medical School? 3 A Not that I recall. 4 Q Do you remember the 5 indication that that particular antibiotic was 6 being investigated for? 7 A No. 8 Q What clinical trial work 9 did you do at the Cleveland Clinic? 10 A Again, antibiotic related 11 or testing of antibiotic. 12 Q Were you a principal 13 investigator on any of those drugs? 14 A Yes. 15 Q Who was the manufacturer 16 of the drugs on which you were the principal 17 investigator? 18 A Merck, Squibb, Lilly, 19 possibly also Upjohn. 20 Q Was the Lilly compound a 21 compound that was patented by Lilly and approved 22 by the FDA for public use? 23 A Subsequently approved. 24 Q What was the name of that 41 1 drug? 2 A The last one was called 3 moxalactam. 4 Q What is that used for? 5 A Serious infections. 6 Q And by virtue of your 7 saying the last one, apparently there were other 8 Lilly drugs that you worked on? 9 A Yes. 10 Q What were they, sir? 11 A Tobramycin and 12 Cephamandole. 13 Q And what were the 14 indications for those products? 15 A Serious infection. 16 Q Any particular type of 17 disease that that was being investigated for? 18 A The diseases related -- 19 the drugs were being tested to look at their 20 affect on certain bacteria, so it was not the 21 disease so much as the bacteria which caused the 22 disease. 23 Q What illness did the 24 bacteria produce in humans? 42 1 A In some people it 2 produced what is called bacteremia, in other 3 people it produced what is called endocarditis, in 4 some people it produced what is called septic 5 arthritis. 6 Q Is that where you 7 developed your interest in potential employment 8 with a pharmaceutical firm, by virtue of the 9 clinical trial work that you had done? 10 A No. 11 Q Did you find that 12 clinical trial work interesting? 13 A Yes. 14 Q Did you intend, when you 15 joined Lilly, to do clinical trial work? 16 A Can you define what you 17 mean by do clinical trial work? 18 Q Well, I guess you would 19 have assumed that you would not have been an 20 investigator in a clinical trial, is that correct? 21 A Correct. 22 Q Would you have been 23 coordinating clinical trial work? 24 A Coordinating in the sense 43 1 of setting strategies, but not necessarily, not at 2 all doing the specific trials or planning specific 3 protocols. 4 Q Why did you not want to 5 be involved in planning specific trials and 6 drafting protocol? 7 A Because my interest was 8 in expanding clinical trials at Lilly on a more 9 global basis, and I felt that the specific 10 designing of clinical trials or protocols should 11 be left to those people expert in the area. 12 Q We have used the term 13 medical monitor in connection with clinical 14 trials. Did you ever function as a medical 15 monitor in any clinical trials at Lilly? 16 A No. 17 Q Would it be accurate to 18 state that medical monitors reported to you 19 concerning the activities of their clinical 20 trials? 21 A Yes. 22 Q I'm not interested in the 23 names of any products under investigation by Lilly 24 other than Prozac, unless those products were 44 1 marketed by Lilly; do you follow me? I'm going to 2 ask you some questions about the clinical trials 3 that you were involved in. 4 How many products were 5 under investigation that you dealt with in your 6 capacity as Director of Internal Medical Affairs 7 at Lilly? 8 A International Medical 9 Affairs. 10 Q International. 11 MR. MYERS: Now, are you 12 talking about psychiatric type -- 13 MR. SMITH: No, I'm 14 talking about all products manufactured by Lilly 15 that he was involved with in his capacity as 16 Director of International Medical Affairs. 17 A Probably eight or ten. 18 Q Were there any of those 19 compounds that were CNS compounds other than 20 fluoxetine hydrochloride? 21 A Yes. 22 Q How many? 23 A One. 24 Q And was that compound 45 1 marketed by Lilly? 2 A Yes. 3 Q What was the name of that 4 compound, sir? 5 A Pergolide. 6 Q Pergolide? 7 A Pergolide. 8 Q And pergolide is a -- 9 A Anti-Parkinson's drug. 10 Q So pergolide and Prozac 11 were the only two CNS drugs? 12 A That I was involved -- 13 that were being developed when I was Director of 14 International Medical Affairs. 15 Q Have there been other CNS 16 drugs that have come under your jurisdiction 17 involved in outside US clinical trials since 18 pergolide and Prozac? 19 A Yes. 20 Q Give me the names of 21 those drugs, if they have been approved for 22 marketing. 23 A None of them have been 24 approved for marketing. 46 1 Q All of them are still 2 currently under investigation? 3 A Or investigation has been 4 discontinued. 5 Q Were there any 6 antidepressants in that group? 7 A Yes. 8 Q Was that other 9 antidepressant a specific serotonin reuptake 10 inhibitor? 11 A No. 12 Q Just the one other? 13 A That I can recall. 14 Q Well, that's all I'm 15 going to ask you throughout these next two days, 16 Doctor, is what you can recall, all right? 17 A All right. 18 Q So you don't need to say 19 that I can recall, I'm assuming that you're going 20 to use your best efforts to recall and tell me 21 what you recall, all right? 22 A All right. 23 Q What was your next job 24 title with Eli Lilly and Company? 47 1 A It was Executive 2 Director. 3 Q Of what? 4 A The title is just 5 Executive Director, Lilly Research Laboratories. 6 Q When did you begin that 7 position? 8 A I believe it was 1985. 9 Q Did your job duties 10 change? 11 A No. 12 Q Lilly has a habit of 13 changing titles, don't they? 14 A I believe so. 15 Q Has that been your 16 observation? 17 A Titles change. 18 Q Who did you report to 19 when you became Executive Director of Lilly 20 Research Labs? 21 A It was still Doctor 22 Emmick. 23 Q And you were still in 24 charge of OUS studies? 48 1 A Yes. 2 Q Is it okay, do you feel 3 comfortable with me designating those studies that 4 you were involved in as OUS studies? 5 A If you choose to, that's 6 Lilly lingo. 7 Q That's where I picked it 8 up. Have you in the past spoken of your 9 responsibilities using the term OUS? 10 A Never. 11 Q Why? 12 A I don't like the term. 13 Q What do you prefer? We 14 don't want to do something with you for two days 15 that you don't like, Doctor. 16 A That's kind of the 17 international. 18 Q International, all 19 right. And how long were you the Executive 20 Director of Lilly Research Labs? 21 A I believe one year. 22 Q Then what was your next 23 position? 24 A Vice President. 49 1 Q Is that the position you 2 occupy today? 3 A Yes, sir. 4 Q Have your areas of 5 responsibilities changed since you became vice 6 president? 7 A They have changed in a 8 variety of ways over these eight years with 9 various things added at various times, always with 10 the international responsibility, which has been 11 constant. 12 Q What other things have 13 been added in addition to the international 14 responsibilities? 15 A For a short time I was 16 responsible for what is called the Lilly Clinic, 17 and for a short time I was responsible for the 18 divisions that developed new drugs for infectious 19 disease and cancer. 20 Q When was it that you were 21 in charge of the Lilly Clinic? 22 A Probably 1989 to 1990. 23 Q Describe for us what the 24 Lilly Clinic is. 50 1 A The Lilly Clinic is, I 2 believe, roughly a sixty-bed facility on two 3 floors of the county hospital, Wishard Hospital in 4 Indianapolis, and it is a place where Lilly 5 performs some of it's phase one trials in humans 6 and does some of the pharmacokinetic trials of new 7 drugs. 8 Q Is it exclusively related 9 to clinical trial work, the Lilly Clinic? 10 A Yes, it's not an 11 inpatient care facility. 12 Q Is there an inpatient 13 care facility that's set up specifically for Lilly 14 employees here in Indianapolis? 15 A Not that I'm aware of. 16 Q Were you responsible 17 during this period of time for the day-to-day 18 overseeing of the Lilly Clinic or was this just 19 one particular area that was added to the lines 20 under your name? 21 A There was another 22 individual who was responsible for the day-to-day 23 management of the clinic who reported to me. 24 Q How long did you have the 51 1 area of infectious diseases and cancer? 2 A I believe two years. 3 Q What two years would that 4 be? 5 A 1990 to 1992. 6 Q Did that involve the 7 research that Lilly was doing into infectious 8 diseases and cancer? 9 A It involved the clinical 10 research in those areas. 11 Q Which would have been 12 phase two, three and four? 13 A Phase one, two, three and 14 four. 15 Q And would that be like 16 the Lilly Clinic, you didn't directly oversee 17 that, but had somebody that did that through you? 18 A Yes. 19 Q And reported to you? 20 A Yes. 21 Q Any other added 22 responsibilities other than your main 23 responsibility of the international area? 24 A No. 52 1 Q Who did you report 2 directly to when you became Vice President of 3 Lilly Research Labs? 4 A It changed. Initially, I 5 continued to report to Doctor Emmick. 6 Q What was his position at 7 that time? 8 A Vice president also. For 9 a number of years after Doctor Emmick left the 10 medical part of the company, for almost four years 11 I reported directly to Doctor Perelman, President 12 of Lilly Research Laboratories, and then over the 13 course of the years 1990 to '93, I reported to 14 Doctor Thompson. 15 Q What was his position 16 during that time? 17 A Initially it was Vice 18 President of Lilly Research Laboratories, and at 19 some time it was changed, I believe, to Executive 20 Vice President of Lilly Research Laboratories. 21 Q Was he an officer of Eli 22 Lilly and Company at any time during that period 23 of time? 24 A I'm not aware that he was 53 1 or wasn't. 2 Q All right. And now to 3 whom do you report? 4 A Mr. Michael Hanson, who 5 is Vice President of Lilly Research Laboratories. 6 Q And is Mr. Hanson the 7 Vice President of Medical Division? 8 A Yes. 9 Q But he's not a medical 10 doctor? 11 A No. 12 Q Does he have any 13 scientific training? 14 A I believe he graduated in 15 pharmacy. 16 Q And Doctor Leigh Thompson 17 was the vice president in charge of the Medical 18 Division from 1990 to 1993, would that be 19 accurate? 20 A Yes. 21 Q Are you currently seeking 22 or are you currently being reviewed for any type 23 of change in position at Lilly? 24 A Not that I'm aware of. 54 1 Q In other words, there's 2 not another vice presidency or a move one way or 3 the other that you're contemplating? 4 A Anything is possible. 5 Q But there's nothing 6 actively going on that you're aware of? 7 A Not that I'm aware of. 8 Q Or that you are actively 9 seeking? 10 A No. 11 MR. FREEMAN: Let's take 12 a little break. 13 (SHORT BREAK TAKEN.) 14 Q (BY MR. SMITH) Doctor, 15 have you ever given a deposition before? 16 A No. 17 Q Have you ever served as 18 an expert witness in any litigation? 19 A Yes. 20 Q Tell me about that, sir. 21 A On a few occasions when I 22 was on the faculty of the University of 23 Pennsylvania, I served as an expert witness in 24 cases that had to do with infectious diseases. 55 1 Q There are a couple of 2 experts there in malpractice cases, and I don't 3 remember their names. When you had these 4 additional responsibilities such as the Lilly 5 Clinic and this work in infectious diseases and 6 cancer, I got the impression that those were 7 duties that were just duties in addition to your 8 primary responsibilities of international 9 research, is that correct? 10 A That's correct. 11 Q In other words, they 12 didn't come in and require your entire focus? 13 A No. 14 Q And throughout this 15 period of time that you have been with Lilly, your 16 entire employment with Lilly, your primary focus 17 has been in international research at Lilly? 18 A Correct. 19 Q In addition to being an 20 expert witness, have you ever testified as a 21 witness of any kind in any trial or in any 22 deposition? 23 A No. 24 Q I would like to go back 56 1 with you in your employment with Lilly and start 2 asking you specifically -- get some idea 3 specifically of your interactions with fluoxetine 4 hydrochloride, Prozac. When you came with Lilly 5 in 1983, Prozac or fluoxetine hydrochloride was a 6 compound under investigation at Lilly, was it not? 7 A Yes. 8 Q At that time, it had not 9 been granted approval to be marketed in any 10 country in the world, had it? 11 A That's correct. 12 Q What were your first 13 responsibilities in connection with work on 14 Prozac? And I'm going to use the term Prozac, 15 fluoxetine hydrochloride, I'll be using Fluctin, 16 all of those interchangeably for that compound; 17 are we straight there? 18 A Yes. I had no specific 19 responsibility with regard to fluoxetine when I 20 first came to Lilly. 21 Q When did you first start 22 having any responsibility in connection with 23 fluoxetine? 24 A After submissions had 57 1 been made to various governments and questions had 2 arisen from those governments to clarify 3 scientific information. 4 Q Were you responsible for 5 the registration of Prozac in any country? 6 A Can you define 7 responsible? 8 Q Where you were doing work 9 in connection with regulatory activities, you 10 know, filing applications in various 11 jurisdictions, compiling things such as IND's or 12 NDA's within the United States, whatever their 13 cousins could be called in foreign countries? 14 A No, I had no involvement 15 with that. 16 Q Would it be accurate to 17 state that your responsibility was within the 18 medical division when a foreign country would have 19 a specific question concerning the compound, that 20 you would seek to coordinate the securing of the 21 medical data that was needed? 22 A Yes. 23 Q Prior to your coming with 24 Lilly, what was your understanding concerning who 58 1 was doing those functions with respect to Prozac? 2 A Can you define what you 3 mean by those functions? 4 Q Answering the medical 5 questions that were raised by foreign countries. 6 A Prior to my joining 7 Lilly, submissions for Prozac or fluoxetine had 8 not been made in any country that I'm aware of, 9 and so there were no questions being asked by 10 regulatory agencies that I'm aware of. 11 Q There were clinical 12 trials being done on an international basis 13 involving Prozac, were there not? 14 A Yes. 15 Q And those had been in 16 existence prior to your coming to Lilly? 17 A Yes. 18 Q Tell me what the status 19 of those trials were, generally. 20 A I believe some of them 21 were completed and some of them were still ongoing 22 at the time that I joined Lilly. 23 Q Who was responsible for 24 overseeing that foreign work prior to your 59 1 arriving at Lilly? 2 A I believe it was a 3 combination of the Lilly medical people in the 4 country where the study was being performed, and 5 also the Lilly medical monitor in Indianapolis. 6 Q Who would that have been 7 in connection with Prozac? 8 A Doctor Paul Stark. 9 Q Doctor Stark left in 10 1984, the summer of 84; is that your recollection? 11 A I don't recall the 12 specific date, but I recall him leaving about that 13 time. 14 Q The reason I can remember 15 that is not only because I have a photogenic 16 memory, I remember everything that was said, but 17 because he was here yesterday talking to us. I'm 18 not under oath, additionally. 19 MR. BROWN: But he does 20 keep a careful check on the reporter for accuracy. 21 Q But you were under the 22 impression that Doctor Stark was doing this work 23 within the medical division in connection with 24 Prozac for foreign trials? 60 1 A My believe is that it was 2 a cooperative effort between Doctor Stark and the 3 Lilly medical personnel in the country where the 4 trial was being performed. 5 Q Approximately how many 6 clinical trials were ongoing in connection with 7 Prozac at the time you started? 8 A I really don't know. 9 Q Do you know of any that 10 were complete? 11 A My assumption is that 12 there were a number that were complete because at 13 the time I joined Lilly, preparations were being 14 made for the submission of the data to various 15 governments, but I don't know the specific number. 16 Q Can you recall what 17 governments the submission process was already 18 instigated in when you began? 19 A My impression is that the 20 dossier had not been submitted anywhere when I 21 began in June of 1983. 22 Q Then would you have been 23 involved in selecting various countries to present 24 this data to, to make application to market the 61 1 product? 2 A No. 3 Q Who would have done that? 4 A I'm not sure who would 5 have done that; I don't know what the process was. 6 Q Once you came on board, 7 how was it decided to choose a particular company 8 to seek approval in and maybe defer or not select 9 a particular country? 10 A I don't recall a 11 situation during my tenure that that kind of 12 decision has been made. Our view has been that 13 when we develop new compounds, we should attempt 14 to register them worldwide. 15 Q Well, does that mean that 16 somebody at Lilly goes to every country on the 17 globe and attempts to register a Lilly product? 18 A I would not say every 19 country on the globe, but I would say literally 20 scores of countries. Understanding the regulatory 21 requirements of those countries, we will attempt 22 to register the product, get the product approved, 23 anywhere it is possible to get it approved. 24 Q How is the decision made 62 1 on which country to select first? Let me give you 2 an example: Let's say you've got Mexico, Japan, 3 Germany, Zaire, Rwanda and Czechoslovakia. Is 4 there still a Czechoslovakia? 5 A No. 6 Q In 1983 there was still a 7 Czechoslovakia. Obviously Lilly is going to have 8 some selection concerning how they're going to 9 approach a set of countries. Give me some insight 10 as to how that selection process goes. 11 A There are a group of 12 countries which have regulatory requirements which 13 are somewhat similar. Those countries include the 14 US, Canada, Western Europe, Australia, South 15 Africa, New Zealand, and in those countries, data 16 that has been generated by a company, Lilly or 17 other companies, can generally be submitted in 18 roughly the same fashion to all of those 19 countries. The other countries of the world, such 20 as those in Asia or Africa or Latin America, have 21 different requirements, and it is not possible to 22 submit data to those countries at the same time as 23 one does to the more developed countries. In 24 fact, most of those countries require proof that a 63 1 drug has been approved in one or more of the 2 developed countries before they will consider 3 registering it in their country. 4 Q You mean one of the 5 developed countries requires proof of registration 6 or a country in Asia, Africa or Latin America will 7 require that it be registered in one of the more 8 developed? 9 A A country in Asia, Africa 10 or Latin America generally requires proof that the 11 drug is approved in one or more of the developed 12 countries. 13 Q I would assume then that 14 you would focus your activities in registering the 15 product in one or more of the developed countries? 16 A In all of the developed 17 countries, if it's possible. 18 Q Can you tell me what 19 countries Lilly had clinical trials ongoing 20 concerning Prozac in when you began? 21 A No, I know there were 22 trials going on in other countries, but I don't 23 know specifically in June of 1983 which countries 24 those were. 64 1 Q But at some point, all of 2 that data would have come under your purview as 3 Director of International Medical Affairs? 4 A No. 5 Q Okay, why not? 6 A My job was twofold; as I 7 mentioned, to stimulate more clinical research in 8 foreign countries, and also to facilitate. As you 9 indicated in the response to questions, it was not 10 necessary for me to be familiar with the details 11 of every trial in every country. 12 Q All right. If there was 13 a trial ongoing in, say, England, obviously that 14 trial would have a medical monitor responsible for 15 that particular trial? 16 A Yes. 17 Q That wouldn't be you? 18 A No. 19 Q You've never been the 20 medical monitor of any clinical trial I think you 21 said, is that correct? 22 A Correct. 23 Q But would it be that that 24 medical monitor would be reporting to you on 65 1 questions raised by that trial? 2 A No, not necessarily. If 3 there were questions raised by that trial, the 4 medical monitor would be interacting with those 5 who were expert in the field, who would be the 6 scientists and medical monitors here in 7 Indianapolis at the world headquarters. 8 Q So your duties were to 9 facilitate the coordination of this, though? 10 A Yes. 11 Q During the first two 12 years, or by the time you had just left as the 13 Director of International Medical Affairs, what 14 percentage of your work would have been involved 15 in Prozac as opposed to other compounds? 16 A A distinct minority, 17 twenty percent or less of my time. 18 Q Did it ever increase to 19 where you were devoting a greater percentage of 20 time to issues raised by Prozac? 21 A I don't recall that, no. 22 Q And did you say that 23 within the last year your duties have not included 24 any work in connection with Prozac? 66 1 A I've had no specific 2 involvement with Prozac in the last year that I 3 can recall. 4 Q Do you know why? 5 A There hasn't been 6 anything that's occurred that would necessarily 7 involve me. 8 Q Would your involvement 9 usually be raised when there is some regulatory 10 issue of a medical nature presented? 11 A That is one of the 12 instances in which I might be involved, yes. 13 Q Explain to me the other 14 instances which you might be involved. 15 A If we were attempting to 16 begin trials in an area of the world where we had 17 not done trials before, I might be involved in 18 going to the country and meeting experts in the 19 field, I might be involved in understanding the 20 regulatory requirements in that country in greater 21 depth than I did before I went, so there would be 22 involvement other than regulatory concerns. 23 Q What other instances 24 would require your input? 67 1 A The only other instances 2 which would require my involvement would be those 3 in which the company wanted to present itself in 4 the most positive light to the medical community, 5 and I have functioned on occasion around the world 6 as what one might call a good will ambassador for 7 the company, and have in that vein interacted with 8 a number of people who might be prescribers of 9 Prozac or might be investigators of Prozac or 10 might be interested in Prozac. 11 Q Were you involved in 12 securing any investigators for any studies outside 13 the United States on Prozac? 14 A Can you define securing? 15 MR. FREEMAN: Do you mean 16 selecting? 17 MR. SMITH: That's a good 18 word, Joe, thank you very much. 19 A On one occasion. 20 Q Tell me about that. 21 A On the occasion of doing 22 a study which is currently ongoing in Taiwan, I 23 was involved in selecting the investigator. 24 Q What study was that, is 68 1 that Doctor Lu's study? 2 A That's Doctor Lu's study. 3 Q We're going to talk about 4 that. 5 A I'm sure we are. 6 Q What gave you the 7 impression we'd be talking about that? 8 A Noticing the smiles 9 around the table when I mentioned Taiwan. 10 Q Any other instances where 11 you selected investigators in foreign countries? 12 A No. 13 Q Do you know Doctor Stuart 14 Montgomery? 15 A Yes. 16 Q How did you first meet 17 Doctor Stuart Montgomery? 18 A I met him, I believe, 19 when he was a speaker at a Lilly symposium that I 20 attended. 21 Q Where? 22 A In Italy. 23 Q Montenico? 24 A Montecatini. 69 1 Q Did you go with Doctor 2 Stark to that symposium? 3 A He and I were two of a 4 number of Lilly attendees; I didn't specifically 5 go with him. 6 Q I understand, but you 7 were there at the same time? 8 A I was there at the same 9 time that Doctor Stark was there. 10 Q And that was a symposium 11 in connection with Prozac, was it not? 12 A Yes. 13 Q And Doctor Stuart 14 Montgomery is a eminent psychiatrist? 15 A Yes. 16 Q And he is a psychiatrist 17 that is especially knowledgeable concerning 18 suicides; is that your understanding? 19 A That's not my 20 understanding. 21 Q What is your 22 understanding concerning Doctor Stuart 23 Montgomery's expertise? 24 A My understanding is that 70 1 he is an eminent psychiatrist in the United 2 Kingdom and Europe, and that he has cooperated 3 with another eminent psychiatrist in Europe in 4 developing one of the rating scales that is used 5 for depression. 6 Q Who is that other eminent 7 European psychiatrist? 8 A Doctor Marie Osberg from 9 Sweden. 10 Q What was the subject of 11 your discussions with Doctor Montgomery in -- I 12 guess that would have been '83 or '84, wouldn't 13 it, probably '84? 14 A I believe it was 1984. 15 I'm not sure whether it was 1984; it was not 16 1983. It may have been '84 or '85, I really don't 17 recall. 18 Q The reason I can 19 pinpoint '84 is because Doctor Stark left in July 20 of '84, he went to this symposium. Now you tell 21 us you were there. 22 A I accept your dating. As 23 I recall, I had brief contacts with Doctor 24 Montgomery that were purely on a social basis, and 71 1 I believe I was involved in perhaps one meeting 2 that had to do, I believe, with a publication that 3 he was about to prepare. 4 Q In '84? 5 A At the Montecatini 6 meeting. 7 Q Do you have any 8 recollection of what that publication was? 9 A No. 10 Q Do you have a 11 recollection of whether or not Doctor Montgomery 12 was doing any clinical trial work on Prozac at the 13 time? 14 A I don't recall whether he 15 was at the time, no. 16 Q Well, he has since, 17 hasn't he? 18 A I believe so. 19 Q Tell me about the 20 clinical trial work that Doctor Montgomery has 21 done of which you are aware? 22 A Honestly, I'm not 23 familiar with the clinical trial work that Doctor 24 Montgomery has done other than to know that he has 72 1 done clinical research using fluoxetine, and that 2 he has done clinical research using all of the new 3 antidepressants and, I believe, other psychiatric 4 medicines as they have been developed. 5 Q Well, are you familiar 6 that Doctor Montgomery has done clinical trial 7 work using fluoxetine to examine the question 8 concerning whether or not there is any causal 9 connection between fluoxetine and suicidality or 10 violent aggressive behavior? 11 A I have heard second or 12 thirdhand that he has done such work, but I am not 13 personally familiar with the work. 14 Q But do you understand 15 that that's a Lilly trial? 16 A I accept your statement 17 that it is. 18 Q All right, but you don't 19 know for sure? 20 A I am not personally 21 involved in the placement, other than the one 22 situation I told you, of clinical trials or the 23 selection of investigators. That is left to the 24 people who are expert in the therapeutic area. 73 1 Q I understand that, but my 2 impression is that you are the individual in 3 medical who is responsible ultimately for all 4 international clinical research done by Eli Lilly 5 and Company; is that correct, Doctor? 6 A That's correct. 7 Q So my question is, I 8 would think you would have some knowledge 9 concerning generally what research would be 10 conducted on an international level? 11 A At the present time, and 12 starting in the mid to late 1980's, as much as 13 fifty to sixty percent of the clinical trial work 14 that is done in all areas in Lilly is done outside 15 the United States. My job is not to know the 16 specific trials done by specific individuals, but 17 rather to facilitate that those trials be 18 performed. And, so, I honestly do not recall 19 specific trials of Doctor Montgomery or any other 20 psychiatrist. 21 Q Well, you do know that 22 these lawsuits raise the issue of suicidality and 23 Prozac, do you not? 24 A Yes. 74 1 Q This has been a 2 significant issue in the media and at Lilly for 3 some time now, hasn't it? 4 A Yes. 5 Q Haven't you tried to make 6 yourself knowledgeable concerning any 7 international studies having to do with the 8 subject of Prozac and suicidality or Prozac and 9 aggressive violent behavior? 10 A I have felt that it was 11 important that I have a general understanding of 12 the issues, and that the specifics of the analysis 13 of trials or the discussion of trials be left to 14 people, many of whom we have, who are expert in 15 the field, and so I have not felt responsible. I 16 have many other responsibilities than Prozac or 17 central nervous system disease drug development, 18 and so with the expertise that we have at Lilly, I 19 felt it's appropriate that they be the ones, the 20 experts, that are most familiar with these 21 details. 22 Q Who would you suggest 23 that I talk to that would be expert at Lilly 24 concerning the details of the scientific work 75 1 being done on an international basis in connection 2 with these issues of suicidality and Prozac and 3 violent aggressive behavior and Prozac? 4 A I would suggest either 5 Doctor Charles Beasley or Doctor Gary Tollefson. 6 Q Why do you mention Doctor 7 Beasley's name? 8 A Because he is an expert 9 psychiatrist. 10 Q Do you know he's never 11 treated a patient with Prozac? 12 A I'm not familiar with his 13 medical history of practice. 14 Q What lends you to believe 15 that Doctor Charles Beasley is an excellent 16 psychiatrist? 17 A He has been trained very 18 well in psychiatry, he has written in the 19 psychiatric literature, I have watched him 20 interact with leading psychiatrists who have told 21 me that they respect his judgment and respect his 22 psychiatric knowledge. 23 Q Who has told you that? 24 A Outside psychiatrists. 76 1 Q That's my question, who 2 are they? 3 A One is Doctor David 4 Dunner from the University of Washington in 5 Seattle, that I recall. 6 Q He's on Lilly's 7 Psychiatrist Advisory Board, isn't he? 8 A I don't know. 9 Q He conducts clinical 10 trials for Lilly, doesn't he? 11 A I don't know that either. 12 Q He conducts clinical 13 trials on Prozac -- has conducted clinical trials 14 on Prozac for Lilly, hasn't he? 15 A I don't know. 16 Q What other 17 internationally-known psychiatrist has spoken 18 highly of Doctor Charles Beasley as a 19 psychiatrist? 20 A I believe on one occasion 21 I spoke with Doctor Stuart Montgomery, and he told 22 me that he was impressed with Doctor Beasley's 23 understanding and knowledge. 24 Q When was that? 77 1 A Sometime within the last 2 four to five years. 3 Q The subject then must 4 have come up concerning Prozac and suicide, 5 because Doctor Beasley and Doctor Montgomery we 6 know have dealt specifically with that issue. 7 Were you and Doctor Montgomery discussing Prozac 8 and suicidality or Prozac and aggressive violent 9 behavior when this discussion of Doctor Beasley 10 came up? 11 A I've never discussed 12 those subjects with Doctor Montgomery. 13 Q Then how did Doctor 14 Montgomery raise the issue of Doctor Beasley? 15 A As I recall, in a 16 perfectly pleasant social setting in which he said 17 that he was impressed that we had some excellent 18 psychiatrists on our staff. 19 Q Did he mention Doctor 20 Beasley by name? 21 A Yes. 22 Q Did he mention anybody 23 else? 24 A He may have mentioned 78 1 Doctor David Wheadon. 2 Q What was this discussion 3 that you were having four or five years ago with 4 Doctor Montgomery? 5 A Can you explain what you 6 mean, what was the -- 7 Q You say it was in a 8 social setting. Were you discussing any type of 9 scientific issues? 10 A Frankly, I don't recall 11 where it was, other than it was not in the United 12 States, and I recall that we have seen each other 13 on occasion on events that have nothing to do with 14 Lilly or with his clinical trial activity, and we 15 have had discussions about a variety of things 16 that are not Prozac related. 17 Q All right. Let me see if 18 I understand this correctly, Doctor. Is it your 19 testimony here that you, as the vice president of 20 Lilly Research Labs, charged with the 21 responsibility of international scientific 22 research on Prozac, have never discussed with 23 Doctor Stuart Montgomery anything concerning the 24 issue of Prozac and its relationship to 79 1 suicidality or Prozac and its relationship to 2 violent aggressive homicidal behavior? 3 A That is correct. 4 Q All right. And you are 5 not aware of any clinical trials that Doctor 6 Montgomery might have in the past or might be 7 currently involved in in connection with Prozac? 8 A As I said, I'm aware that 9 he has performed clinical trials with Prozac 10 sometime in the past. 11 Q But that's all you know? 12 A That's all I know. 13 Q You don't know anything 14 concerning the objective of that clinical trial? 15 A Not specifically. 16 Q The results of that 17 clinical trial? 18 A Not specifically. 19 Q Well, generally? 20 A Generally my impression 21 is that he found Prozac to be a safe and effective 22 antidepressant. 23 Q All right. Do you know 24 what type of patients he was studying Prozac -- he 80 1 was administering Prozac to to make that 2 determination? 3 A No. 4 Q Be it depressed 5 individuals, obsessive compulsive individuals, 6 individuals suffering from bulimia, or other 7 disorders? 8 A I don't know. 9 Q Who would you ask at Eli 10 Lilly and Company concerning specifics of any 11 clinical trial data in connection with Prozac that 12 Doctor Stuart Montgomery had done? Who would you 13 go to at Lilly -- 14 A Today? 15 Q -- to get the answers to 16 these questions that I'm posing to you? 17 MR. FREEMAN: In Great 18 Britain or here or -- 19 MR. SMITH: Any studies 20 done by Doctor Stuart Montgomery. 21 A I would probably ask 22 Doctor Charles Beasley. 23 Q Anybody else, because 24 we've asked him and he's unclear, sir? 81 1 A As I mentioned, Doctor 2 Gary Tollefson. 3 Q What is Doctor 4 Tollefson's job title at this time? 5 A I believe it's executive 6 director responsible for the CNS clinical area. 7 Q Is Doctor Tollefson a 8 vice president of Lilly Research Labs? 9 A No. 10 Q Who does Doctor Tollefson 11 report to? 12 A Doctor Steven Paul. 13 Q You don't report to 14 Doctor Steven Paul? 15 A No. 16 MR. SMITH: Do you need a 17 break? You were looking around. This is not an 18 endurance contest, so if you need to take a break, 19 Doctor, let me know. 20 Q I don't want to be 21 repetitive, but I want to make sure I'm clear. Is 22 it your testimony also, Doctor, that you think you 23 never spent more than twenty percent of your time 24 on Prozac or Prozac-related issues since you have 82 1 been with Lilly? 2 A Yes, I may have spent one 3 full week on Prozac and then three full weeks not 4 on Prozac, and I guess it will be how you would 5 like to define time, but I don't believe I've 6 spent more than twenty percent. 7 Q That's going to bring me 8 to my next question. Were there times when Prozac 9 was, for that period of time, be it a week or a 10 month, where you were devoting a substantial 11 amount of time to Prozac? 12 A There were times like 13 that. 14 Q When was the first time 15 like that? 16 A As I recall, it was 17 sometime in 1984 or 1985. 18 Q All right, what was the 19 subject? 20 A I believe it was 21 questions from the German government. 22 Q All right. How much time 23 were you devoting to Prozac at that time, once the 24 question was raised by the German government? 83 1 A Again, it was perhaps 2 thirty or thirty-five percent of my time, and that 3 is because I made one or two trips to Germany. 4 Q Okay, what's the second 5 time? 6 A The second time was a 7 very short period of time, and I can't recall the 8 year, it may have been in the '90s, and that was 9 related to Costa Rica. 10 Q How long a period of time 11 would that have been? 12 A A few days. 13 Q How long was this German 14 government question requiring a substantial amount 15 of your time, the first instance that you spoke 16 of? 17 A The questions came back 18 and forth over, I believe, more than a year, as I 19 recall. It certainly did not involve that much of 20 my time over a year. I had intermittent 21 involvement particularly related to travel to 22 Germany. 23 Q And you think you made 24 one or two trips to Germany? 84 1 A I made one or two trips. 2 Q Then what was the Costa 3 Rica issue? 4 A The Costa Rican 5 government had read newspapers from the United 6 States with many false accusations about 7 fluoxetine and asked us to come discuss those with 8 them, which we did with people in the Ministry of 9 Health. 10 Q This was in the 1990's? 11 A I believe so. 12 Q And had Prozac been 13 approved for use in depression in Costa Rica -- 14 A Yes. 15 Q -- when this issue came 16 up? 17 A Yes. 18 Q Was there a threat by the 19 Costa Rican authorities to withdraw their approval 20 of this product in Costa Rica? 21 A No, there was not a 22 threat. There were questions that were being 23 raised based on the fact that they had, as I 24 mentioned, received copies of newspapers published 85 1 in the United States with a number of flamboyant 2 and false accusations about Prozac. 3 Q What did you do in 4 response to that? 5 A Showed them the data, the 6 scientific data that dealt with Prozac and its 7 effects, and we had a short meeting with people in 8 the Ministry of Health. 9 Q You say we. Did somebody 10 accompany you? 11 A Myself and Doctor David 12 Wheadon. 13 Q You went with Wheadon? 14 A Yes. 15 Q What data did you show 16 them? 17 A I showed them the data 18 demonstrating that there is not an association 19 between Prozac and suicidality. 20 Q What data is that? 21 There's a lot of data out there, Doctor 22 Weinstein. 23 A The data that was 24 subsequently published in the British Medical 86 1 Journal. 2 Q Oh, Doctor Beasley's 3 data, Doctor Beasley's article? 4 A The data that was 5 published in the British Medical Journal, yes. 6 Q What is your 7 understanding of what that data is; what 8 scientific information does that data encompass, 9 Doctor Weinstein? 10 A I'm not sure I understand 11 what you mean by scientific information. 12 Q Obviously that data that 13 you showed them had to do with the use of Prozac, 14 did it not? 15 A Yes. 16 Q And was that clinical 17 trial information, was it adverse experience 18 information, was it spontaneous reports; what data 19 is that that was reported in the British Medical 20 Journal? 21 A Clinical trial. 22 Q Clinical trial data. All 23 clinical trial data that Lilly had? 24 A No, I believe that was 87 1 US-based clinical trial data. 2 Q All US-based clinical 3 trial data? 4 A I believe that it was the 5 controlled clinical trial data. 6 Q Was that all US clinical 7 trial data that was in existence at the time it 8 was published? 9 A I can't answer that. My 10 impression is that it was all of the available 11 controlled clinical trial data. 12 Q My question is did that 13 include all the data on US trials, or do you know? 14 A I don't know. 15 Q Did it include all US 16 clinical data on all controlled clinical trials 17 for all indications? 18 A I'm not sure, I don't 19 know. 20 Q Any other data that you 21 took to the Ministry of Health and in Costa Rica 22 to counteract these allegations that were being 23 made against this drug, other than the Beasley 24 data that was published in the British Medical 88 1 Journal? 2 A I believe that's all the 3 information that we presented. 4 Q So you didn't present 5 them any post-marketing experience data, did you? 6 A No. 7 Q And you didn't present 8 them any foreign clinical trial data either, did 9 you? 10 A No. 11 Q Had Lilly run any 12 clinical trials in Costa Rica at that time? 13 A No. 14 Q For any drug for any 15 indication? 16 A Not that I'm aware of. 17 Q What's the next time that 18 you spent some time over and above the normal time 19 on Prozac-related issues? 20 A At around the same time, 21 within six months we were notified that the 22 government of Thailand had received the same type 23 of press reports that the government of Costa Rica 24 had, and Doctor Wheadon and I went to Thailand. 89 1 Q That's when you enlisted 2 the aid of the United States Embassy? 3 A I did not enlist the aid 4 of the United States Embassy. 5 Q Who did? 6 A I believe they were 7 contacted by someone at Lilly, but I don't know 8 whom. 9 Q Who at Lilly -- well, you 10 say you don't know who? 11 A I don't know. 12 Q Is there a governmental 13 affairs department at Lilly that interfaces with 14 the United States government? 15 A There is a Washington 16 office that interfaces with the United States 17 government, that's not in Indianapolis. 18 Q Lilly maintains a 19 Washington office for the purposes of interfacing 20 with the United States government? 21 A As do all pharmaceutical 22 companies and other companies. 23 Q But Lilly does? 24 A Yes. 90 1 Q And I assume that office 2 coordinates questions or issues raised by members 3 of Congress or whatever? 4 A Whatever. 5 Q Who was heading that 6 office when you went to Thailand? 7 A I don't recall. 8 Q Does the name Mitch 9 Daniels ring a bell? 10 A He would not have headed 11 that office. It rings a bell, but he would not 12 have headed that office. 13 Q What is your 14 understanding of what Mr. Mitch Daniels does? 15 A At the present time he 16 runs the US pharmaceutical operation. 17 Q What did he do prior to 18 that? 19 A He was responsible for 20 corporate affairs based in Indianapolis. 21 Q All right. And as part 22 of that, he had to interact with government 23 agencies, did he not? 24 A I believe so. 91 1 Q Did you ever work with 2 him in that connection, Doctor Weinstein? 3 A In interacting with 4 government agencies? 5 Q Yes. 6 A No. 7 Q Did you work with him at 8 all on anything? 9 A I was in meetings with 10 him for a variety of reasons on a variety of 11 issues, but that's all I recall interacting with 12 him on. 13 Q Any meeting or any issue 14 involving Prozac? 15 A There were meetings we 16 were in that involved Prozac. 17 Q Where? 18 A At Lilly. 19 Q I understand, but in what 20 connection was Mr. Mitch Daniels involved? 21 A There was a meeting that 22 took place with the senior executives of the 23 company to review questions that would arise 24 regarding Prozac on the scientific side, on the 92 1 public affairs side, on the regulatory side, and 2 Mr. Daniels was present. 3 Q And those had to do with 4 Prozac and suicide and Prozac and aggressive 5 violent behavior, didn't they? 6 A They had to do with 7 Prozac. 8 Q And those issues were 9 discussed, were they not? 10 A Among other issues, yes. 11 Q I understand there were 12 other issues discussed, but that issue was raised? 13 A Yes. 14 Q When were those meetings? 15 A I don't recall 16 specifically when they began, but they were 17 roughly weekly meetings. 18 Q Were these the Tuesday 19 morning meetings? 20 A Yes. 21 Q Doctor Perelman was 22 there? 23 A Yes. 24 Q Doctor Leigh Thompson was 93 1 there? 2 A Yes. 3 Q Mr. Wood was there from 4 time to time? 5 A Occasionally. 6 Q Mr. Bryson was there from 7 time to time? 8 A Occasionally. 9 Q Mr. Taurel was there from 10 time to time? 11 A Yes. 12 Q Doctor Herr was there 13 from time to time? 14 A Yes. 15 Q And Mitch Daniels, the 16 corporate affairs director? 17 A Yes. 18 Q Was he a regular member 19 of this group? 20 A I am not sure, but I 21 believe so, yes. 22 Q Were you a regular member 23 of that group? 24 A Yes. 94 1 Q And what was your 2 function in these Tuesday morning meetings? 3 A My function primarily 4 was -- or uniquely was to discuss anything that 5 might be happening with regard to international 6 medical questions. 7 Q And Prozac and the issue 8 of suicide, violent aggressive behavior, correct? 9 A Correct. 10 Q The testimony has been 11 that that was the purpose of the Tuesday morning 12 meetings, wasn't it? 13 MR. FREEMAN: That's a 14 mischaracterization of the testimony; it was to 15 keep an update on what was happening with Prozac, 16 not those two issues, and that's not fair to say 17 that, Paul. 18 Q Those two issues were 19 discussed regularly, weren't they, at the Tuesday 20 morning meetings? 21 A Those were two of many 22 issues regarding Prozac that were discussed at 23 those meetings. 24 Q And those two issues were 95 1 discussed regularly, weren't they? 2 A I'd like to know how you 3 characterize regularly. There were meetings that 4 went on in which those two issues were not 5 discussed, and in fact the purpose of the Tuesday 6 morning meeting was to discuss other elements or 7 other factors related to fluoxetine that had 8 nothing to do with either one of those issues. 9 Q Well, if there were four 10 Tuesday morning meetings a month, on three of the 11 four occasions, the issue of Prozac and 12 suicidality and violent aggressive behavior would 13 be raised, would it not? 14 A The issue of either of 15 those issues did come up at the majority of the 16 meetings. 17 Q All right. What other 18 instances would there be times where Prozac would 19 occupy a majority of your time? You've told us 20 about the German government issue, the Costa Rica 21 issue and the Thailand issue. 22 A The only other one was 23 the question that we discussed briefly earlier 24 with regard to Taiwan, which you said you would 96 1 defer until later. 2 Q Well, I don't want you 3 going to sleep on me, I want you to know that 4 something else is coming up. 5 A There's very little 6 likelihood that I will go to sleep. 7 Q Would it be accurate to 8 state that at any time in connection with your 9 dealings with Prozac and the issue of suicide and 10 the issue of violent aggressive behavior, that you 11 never served as an expert concerning the issue 12 presented? 13 A I never served as an 14 expert concerning that issue, that is correct. 15 Q You are not a 16 psychiatrist? 17 A That is correct. 18 Q You are not a 19 psychopharmacologist? 20 A Correct. 21 Q You are not a 22 pharmacologist? 23 A Correct. 24 Q You are not a 97 1 neurologist? 2 A Correct. 3 Q You've never prescribed 4 Prozac? 5 A No. 6 Q You've never treated 7 individuals psychiatrically for problems in 8 connection with suicide or violent aggressive 9 behavior, have you? 10 A No. 11 Q So you don't consider 12 yourself an expert at all in connection with the 13 issues presented by this litigation, do you? 14 A I do not. 15 Q But, as I understand it, 16 you talked with individuals from time to time who 17 do consider themselves expert on this issue? 18 A Yes. 19 Q Give me who you recall at 20 this time, and try to supplement for me if names 21 come to date over the next two -- come to mind 22 over the next two days, individuals who you have 23 talked with that consider themselves expert on 24 these issues, and we mentioned Doctor Stuart 98 1 Montgomery, would he be -- 2 A I have not talked to him 3 on this issue. The names I would give you are the 4 names I have already given you, which I have not 5 talked to anyone outside Eli Lilly and Company. 6 Q And the name you've given 7 me is Doctor Beasley? 8 A Doctor Tollefson, Doctor 9 Wheadon, those are the only people that I have 10 talked to. I have not specifically talked about 11 these questions to any outside psychiatric 12 experts. 13 Q Of individuals in house, 14 would you consider Doctor Leigh Thompson an expert 15 on this issue? 16 A No. 17 Q Would you consider Doctor 18 Bob Zerbe an expert on this issue? 19 A No. 20 Q While we're looking for 21 this document, Doctor, you indicated to me that 22 Doctor Paul Stark had served as the medical 23 monitor on Prozac for some international clinical 24 trials? 99 1 A I believe so. 2 Q When you came? 3 A Yes. 4 Q And was anybody else 5 serving as medical monitor for those trials being 6 done internationally at that time? 7 MR. FREEMAN: You mean 8 including country personnel, country managers or 9 people in England or France? 10 MR. SMITH: No, I'm just 11 speaking of individuals at Indianapolis that would 12 have been coordinating or responsible for those 13 trials. 14 A I'm not aware of other 15 individuals in Indianapolis. There were certainly 16 individuals in each country who worked with Doctor 17 Stark, but I'm not aware of other people here. 18 Q Did Doctor Stark give you 19 any type of breakdown or summary information 20 concerning the status of the international 21 clinical trials at the time you arrived? 22 A I'm sure he must have at 23 some time after I arrived, but I really don't 24 recall specifically. 100 1 Q So what was your 2 perception of the international trials in 3 connection with Prozac that you first recall? 4 A My perception is that 5 there were some clinical trials done 6 internationally on Prozac, that the majority of 7 the clinical trials that were making up the 8 registration dossier had been done in the United 9 States. 10 Q Did you have an 11 understanding at that time concerning whether or 12 not any of the international trials that were 13 being conducted served as part of the data that 14 was going to be submitted to the United States 15 Food and Drug Administration for registration? 16 A I had no idea of that. 17 The submission to the United States FDA was made 18 within a few month of my arriving, and I believe 19 that process was already ongoing before I ever 20 arrived. 21 Q But Doctor Stark didn't 22 make you aware that there was some particular 23 clinical trial that was being conducted in some 24 particular international country that was going to 101 1 be used as part or in toto as a pivotal trial that 2 was going to be submitted to the United States 3 Food and Drug Administration? 4 A I don't recall him making 5 me aware of that, no. 6 Q Do you have a 7 recollection of the location of those 8 international trials when you first came on? 9 A I believe there had been 10 some trials done in the United Kingdom, I believe 11 there had been some trials done in France, and 12 there may have been trials done in Germany, but 13 I'm not sure. 14 Q And applications were in 15 process in Germany, the United Kingdom and in 16 France by 1984, would that be accurate? 17 A I believe so, yes. 18 Q But none of them had 19 actually been submitted prior to your arriving at 20 Lilly? 21 A As far as I'm aware, 22 there had been no submissions to any government 23 before I arrived. 24 102 1 (WEINSTEIN EXHIBIT NO. 1 MARKED FOR 2 IDENTIFICATION.) 3 Q Did Doctor Stark discuss 4 with you at all any issue in connection with 5 Prozac and suicidality or Prozac and violent 6 aggressive behavior? 7 A I don't recall. 8 Q Have you had an 9 opportunity to look at Exhibit 1? 10 A Yes. 11 Q Do you recall receiving 12 that document? 13 A No. 14 Q It's dated June 22, 1984, 15 correct? 16 A Correct. 17 Q And it's a -- what is 18 this, a memo or a telex or an E-mail? 19 A It's a telex, I believe. 20 Q A telex from Doctor Stark 21 to you? 22 A Yes. 23 Q And it is from Florence? 24 A It has an Italian code on 103 1 it, so it's from Italy. 2 Q I see "Florence 22 6 84" 3 on there. 4 A Oh, I'm sorry, yes. 5 Q Is he telexing you from 6 Florence or are you in Florence at this time? 7 A No, he's in Florence. 8 Q What's he doing in 9 Florence? 10 A I have no idea. 11 Q Is this the 12 Montecatini -- 13 A It may have been 14 Montecatini. As best I can tell, the way this 15 telex is written, it appears I am in Indianapolis 16 and he is in Italy. 17 Q All right. It says, "For 18 your instructions, I declined Prof. Hans Weber's 19 request to meet Professor," and then that's marked 20 out. "You may wish to follow through with 21 whatever your plan was. Regards, Stark P.," 22 correct. 23 MR. FREEMAN: Hans Weber 24 must be blocked out. Do you have that on yours? 104 1 MS. ZETTLER: Whoops, two 2 different copies. See, if you guys would get your 3 redacting straight, we wouldn't have this 4 problem. 5 MR. MYERS: We'll have to 6 work on that. 7 Q (BY MR. SMITH) You are 8 looking at a document, Exhibit 1, that has 9 "Fentress Confidential" marked on it, and I was 10 looking at a document that has "Confidential, 11 Subject to Protective Order in MDL Docket 907." 12 It doesn't make any difference which is which, but 13 I just want to show you that I have one where 14 Professor Hans Weber is not marked out. Do you 15 see that? 16 A Yes. 17 Q Hans Weber is actually a 18 Lilly employee in Germany, isn't he? 19 A Yes. 20 Q Was then? 21 A Yes. 22 Q Is now? 23 A Yes. 24 Q And Professor Weber -- 105 1 he's not a professor of anything, is he? 2 A I'm not aware that he's a 3 professor. 4 Q That may be a typo. Who 5 is this other individual that's blocked out? 6 A I have no idea. 7 MR. SMITH: Do you all 8 know who it is? 9 MR. MYERS: I don't know. 10 MR. SMITH: Can you get 11 us that information? 12 MR. MYERS: I'll look 13 into it. 14 MR. SMITH: Thank you. 15 Where do you look when you look? 16 MR. FREEMAN: We'll think 17 about it, let's put it that way, we'll consider 18 it. 19 MR. MYERS: That would be 20 confidential, a trade secret. 21 Q (BY MR. SMITH) Would it 22 be Professor Mobious? 23 A I don't know. 24 Q Do you know Professor 106 1 Mobious? 2 A I know his name; I don't 3 believe I've ever met him. 4 Q What do you know about 5 Professor Mobious? 6 A I know that he is a well- 7 known German critic of the pharmaceutical 8 industry. 9 Q Well, he was formerly the 10 chairman of the BGA, the German equivalent of the 11 FDA, wasn't he? 12 A That I was not aware of. 13 Q You didn't know that? 14 A No. 15 Q Do you have any idea what 16 Doctor Stark is talking about in this exhibit? 17 A No. 18 Q It says, "You may wish to 19 follow through with whatever your plan was." Do 20 you remember what your plan was? 21 A I do not remember any 22 plan. 23 Q Can you tell us anything 24 about it by virtue of the fact that it's got 107 1 Doctor Zerbe and -- is it Doctor Emmick's name on 2 there? 3 A Yes. No, that doesn't 4 help me identifying what this is about. 5 Q Does it help you that it 6 probably has to do with Prozac or Fluctin or 7 fluoxetine hydrochloride? 8 A I don't see any evidence 9 that it has to do with that; it might. 10 Q Doctor Zerbe wasn't 11 working on any other drugs at the time? 12 MR. FREEMAN: No, no, no, 13 Doctor Stark, not Doctor Zerbe. 14 MR. SMITH: Doctor Zerbe 15 is mentioned on here as a CC. 16 MR. FREEMAN: You said 17 Doctor Zerbe was not working on any other drugs at 18 the time? 19 MR. SMITH: Yes. 20 A I don't believe that's 21 correct. As a matter of fact, I know he was 22 working on at least pergolide. 23 Q Do you think this has to 24 do with pergolide? 108 1 A I don't know what it has 2 to do with. As I told you, I don't know what it's 3 about, I don't know which plan they are referring 4 to, and although I know who Doctor Mobious is, I 5 don't know what the interaction between Hans Weber 6 and Mobious would have been. 7 Q In June of 1984, was 8 there any problem in connection with Prozac in 9 Germany? 10 A There was an ongoing 11 interchange, and I'm not sure of the date, it may 12 well have been sometime in 1984, between Lilly and 13 the German government regarding Prozac. 14 Q Did that problem involve 15 Prozac and suicide and Prozac and violent 16 aggressive behavior? 17 A Not that I'm aware. 18 (SHORT BREAK TAKEN.) 19 (WEINSTEIN EXHIBIT NO. 2 MARKED FOR 20 IDENTIFICATION.) 21 Q (BY MR. SMITH) Have you 22 had an opportunity to examine Exhibit 2, Doctor 23 Weinstein? 24 A Yes. 109 1 Q And that exhibit is dated 2 four days after Exhibit 1; it's dated June 26, 3 1984, correct? 4 A Correct. 5 Q I believe it was your 6 testimony earlier that on June 22, 1984 you were 7 not aware of a problem in Germany in connection 8 with the issue of Prozac and suicidality or Prozac 9 and violent aggressive behavior, is that correct? 10 A Correct. 11 Q You are an addressee or 12 received a copy of the document marked Exhibit 2, 13 correct? 14 A Yes. 15 Q And this is a telex from 16 Doctor Weber and Doctor Schenk in Germany, is it 17 not? 18 A Yes. 19 Q And you know them? 20 A Yes. 21 Q You knew them then? 22 A Yes. 23 Q You know them now? 24 A I haven't seen Doctor 110 1 Schenk in many years. I know Doctor Weber. 2 Q Doctor Schenk is still a 3 Lilly employee, is she not? 4 A Not that I'm aware of. 5 Q When did Doctor Schenk 6 leave Lilly? 7 A Sometime in the mid 8 1980's, I believe. 9 Q Why did Doctor Schenk 10 leave? 11 A I have no idea. 12 Q This document indicates 13 that there were discussions with the BGA on June 14 15, 1984, does it not? 15 A Yes. 16 Q And it indicates a 17 variety of issues that the BGA was examining, 18 correct? 19 A Correct. 20 Q And the BGA, for the 21 record, is the German equivalent of the United 22 States Food and Drug Administration, correct? 23 A Correct. 24 Q They are the regulatory 111 1 body in Germany that is responsible for insuring 2 that products are safe and efficacious, correct? 3 A Correct. 4 Q And as I believe you 5 said, Germany is one of the developed countries 6 that it is required from some of the undeveloped 7 countries that registration be approved in before 8 the undeveloped country will consider it for 9 approval? 10 A Germany could be one of 11 the developed countries, yes. 12 Q It indicates that, in the 13 first paragraph, "All the issues were subject to 14 various discussions with medical marketing 15 personnel on the occasion of the Fluoxetine 16 Symposium/14th C.I.N.P. Congress," correct? 17 A Correct. 18 Q What is the C.I.N.P. 19 Congress? 20 A It's a worldwide medical 21 meeting of, I believe, neurologists and 22 psychiatrists that was held in Florence in 1984. 23 Q Could that have been 24 where Doctor Stark was when he authored Exhibit 1 112 1 four days earlier, because it comes from Florence, 2 doesn't it? 3 A The only thing I can say 4 about that, it has the code of the Lilly office in 5 Florence, and I can state that he sent that from a 6 Lilly -- that was sent from a Lilly office in 7 Florence. I cannot surmise as to whether he was 8 at this meeting. 9 Q Were you at that meeting? 10 A No. 11 Q What does C.I.N.P. stand 12 for? 13 A It is something like 14 Collegium Internationale, the N and the P are 15 neuropsychiatric and they are probably Latin 16 words. It's an international congress or an 17 international college of neuropsychiatry that has 18 a limited attendance, I think -- I believe you 19 have to be an invitee. It occurs once every two 20 years or three years, it does not occur every 21 year. It is occurring as we sit here in 22 Washington because this is the year that it is 23 occurring in the United States. 24 Q Is it kind of the 113 1 Olympics of psychiatry or the World Cup of 2 psychiatry? 3 MR. FREEMAN: Please, 4 please. Next question. 5 A Do you want me to answer 6 that? 7 Q No. But this is 8 apparently an astute body of psychiatrists, is it 9 not? 10 A Apparently. 11 Q Have you ever been to a 12 C.I.N.P. Congress? 13 A No. 14 Q Is anybody at Lilly a 15 member of the C.I.N.P.? 16 A I'm sure there must be 17 some people who are, but I'm not familiar with the 18 specific members. 19 Q But will you agree with 20 me that it is a scientific body of some renown in 21 that particular area, in all seriousness? 22 A Yes, it is not a 23 scientific body, it is a meeting that occurs -- 24 Q Of scientists? 114 1 A -- of scientists, and it 2 is certainly apparently a very high level 3 scientific meeting. 4 Q And apparently, from 5 reading this, all of the issues that were raised 6 by the issues were issues subject to various 7 discussions with the medical marketing persons on 8 the occasion of this meeting of this Congress, is 9 that right? 10 MR. FREEMAN: You're 11 going to have to redo that question because you 12 said meeting on the issues on the issues or 13 something, it's not clear what you asked. 14 Q Well, the issues that 15 were raised by the BGA appear, by virtue of what's 16 written here, were issues that were raised and 17 discussed at this Congress or when there were 18 medical marketing people at the Congress. 19 A That is not my 20 interpretation. 21 Q What is your 22 interpretation? 23 A My interpretation of this 24 is that those issues were discussed during the 115 1 time of the symposium in Montecatini which 2 happened to precede this C.I.N.P. Congress. It is 3 not my interpretation that these issues were 4 discussed at that Congress. 5 Q All right. Then it goes 6 on to talk about the issues that had been raised 7 by the BGA, correct? 8 A Correct. 9 Q And enumerate the 10 concerns of fluoxetine registration in Germany, 11 correct? 12 A Correct. 13 Q And Item 2 says that the 14 BGA stated that there is a disagreement between 15 patient's and doctor's judgment on efficacy since 16 in their, the BGA's opinion, the patient's 17 impression is more important and we have to 18 demonstrate correlation between SCL 58 and HAMD 19 and CGI and PGI response, correct? 20 A I think the R-E-S-P 21 probably means respectively, but, yes. 22 Q Are you familiar with any 23 of this, what the HAMD, the SCL 58 is? 24 A I'm familiar with some of 116 1 these, yes. 2 Q And they are evaluating 3 instruments used in examining the issue of 4 improvement or worsening of depression, are they 5 not? 6 A Yes. 7 Q Item 7 says, "The BGA 8 explained their reservations regarding CNS 9 side-effects," correct? 10 A Correct. 11 Q Were you aware at the 12 time that the German government had reservations 13 concerning CNS side effects presented by Prozac? 14 A I do not recall any 15 preexisting awareness; I may have become aware by 16 reading this telex. 17 Q Well, do you recall 18 reading the telex back in June of 1984? 19 A I don't specifically 20 recall reading this telex, but I will say that I 21 read all of my telexes, so I probably read this 22 one. 23 Q And these are indeed 24 issues, Doctor Weinstein, of a medical nature 117 1 raised by a foreign regulatory body, are they not? 2 A That is correct. 3 Q And therefore it comes 4 directly within your job title and job 5 responsibilities, doesn't it? 6 A No. 7 Q Why not? 8 A Because my job was to 9 facilitate the answering of these questions, and 10 if you would consult the addressee list, you would 11 find that there were qualified people who had much 12 more direct responsibility for this compound who 13 were also copied on this and who were asked, 14 particularly the three primary addressees. 15 Q But you had some 16 responsibility, didn't you feel? 17 A My responsibility was to 18 make certain that answers were provided to the 19 questions that were asked and that those answers 20 were provided in an expeditious scientifically 21 based fashion; my job was not to develop the 22 answers. 23 Q Did you do that in 24 connection with the issues raised by Exhibit 2? 118 1 A As far as I can recall, 2 we eventually were able to answer the questions 3 that the BGA had raised. 4 Q All right. It goes on to 5 say in Point 7, "There have been a few patients 6 complaining of psychosis and hallucinations 7 (sic). Please provide us detailed reports whether 8 these patients suffered from 'psychotic 9 depression', whether the hallucinations developed 10 during treatment or had perhaps been present 11 already at start of treatment, or whether those 12 events may indeed be interpreted by 'aggravation 13 or disease'," correct? 14 A Correct. 15 Q Had you heard of anything 16 of that nature in connection with side effects 17 raised by Prozac? 18 A I don't recall having 19 heard about it before receiving -- before I would 20 have received this telex. 21 Q Item No. 10 speaks of 22 comparative use of concomitantly taken hypnotics 23 and benzodiazepines in agitated/retarded 24 fluoxetine patients versus agitated/retarded 119 1 patients on comparators, and it says, "Reason: 2 The BGA suspects fluoxetine to be a stimulating/ 3 activating drug," paren, "side-effect profile, 4 suicides, suicide attempts," close paren, correct? 5 A Correct. 6 Q Do you recall seeing this 7 in June 1984, Doctor Weinstein? 8 A Again, I don't recall 9 specifically, but I must have seen it in June of 10 1984. 11 Q So were you aware, in 12 June of 1984, of a problem of registering Prozac 13 in Germany in connection with the relationship of 14 Prozac and suicide? 15 A I recall that in the 16 summer of 1984 there were a series of questions 17 that spanned a wide territory that the German 18 government had asked regarding a dossier that had 19 been submitted by Prozac. This was one of a 20 number of questions that had been raised. 21 Q Turn to the last page of 22 the document. Looking at Item 14, which says, 23 quote, "As we already explained by our telex to 24 Doctor Zerbe of June 8, '84, we need a careful 120 1 analysis of suicides and suicide attempts: 2 Patient by patient, symptomatology/severity upon 3 entry into the study and week by week until the 4 event occurred, dose of fluoxetine, side-effects, 5 etc. This is a very serious issue in the opinion 6 of the BGA. It might well be that we have to 7 recommend concomitant tranquilizer intake for the 8 first two or three weeks in the package 9 literature," end quote, correct? 10 A Correct. 11 Q Had you heard before this 12 that the BGA considered this suicide activating 13 issue as being a very serious issue? 14 A I'm not sure I understand 15 why you are -- how you are linking activating and 16 suicide from this statement. 17 Q By virtue of Point 10 18 where the Lilly memo or the memo authored by Lilly 19 people in Germany says the BGA suspects fluoxetine 20 to be a stimulating/activating drug, side-effect 21 profile, suicides and suicide attempts, that's 22 where I get that. 23 A Okay. 24 Q Is that unreasonable on 121 1 my part, Doctor? 2 A I understand that. Can 3 you repeat your question, please? 4 MR. SMITH: I doubt it, 5 but she can read did back for you. 6 REPORTER: (READING) 7 Question: Had you heard before this that the BGA 8 considered this suicide activating issue as being 9 a very serious issue? 10 A I don't recall having 11 heard about it before receiving this telex. 12 Q Had you heard about it 13 before today? 14 A Yes. 15 Q When is your first 16 recollection of this being a problem? 17 A My first recollection is 18 sometime around this time, in the summer of '84 or 19 thereabouts. 20 Q Have you ever seen the 21 telex of Doctor Zerbe of June 8, 1984? 22 A I see reference to it 23 here; I don't recall it. 24 Q Had you ever heard that 122 1 there might be a situation where the BGA would 2 require concomitant tranquilizer intake for the 3 first two or three weeks of Prozac use? 4 A I recall that subject 5 having been discussed, yes. 6 Q But do you recall it 7 being discussed prior to June 26, 1984? 8 A No, I don't recall that. 9 Q What did you do in 10 connection with your receipt of your copy of this 11 telex? 12 A I can't recall. I can 13 tell you only that my habit was not to respond to 14 all telexes and to make certain that the 15 appropriate people were addressed, and as I look 16 at this addressee list, I think the appropriate 17 people who had the data and could analyze the data 18 were, in fact, involved in receiving this telex, 19 and my responsibility would be simply to interact 20 probably on the telephone with Doctor Weber to 21 ascertain that he was getting the information he 22 needed. 23 Q Doctor Stark's name is 24 listed as a primary addressee on Exhibit 2, 123 1 correct? 2 A Correct. 3 Q Who stepped into Doctor 4 Stark's shoes after Doctor Stark left? 5 A I'm sorry, could you 6 repeat that? 7 Q Who stepped into Doctor 8 Stark's shoes after Doctor Stark left? 9 A I believe it was Doctor 10 Joe Wernicke. 11 Q All right. And Doctor 12 Wernicke was the medical monitor responsible for 13 all Prozac trials, domestic and international? 14 A I really don't know. I 15 know he was heavily involved in Prozac and it may 16 have been either domestic or international -- it 17 may have either been domestic or both domestic and 18 international. 19 Q Doctor Wernicke is not a 20 psychiatrist, is he? 21 A No. 22 Q And wasn't at the time 23 either, was he? 24 A I believe not. 124 1 Q Doctor Stark wasn't a 2 psychiatrist then, was he? 3 A No. 4 Q And is not now either, is 5 he? 6 A No. 7 Q Doctor Stark is not a 8 medical doctor, is he? 9 A No. 10 Q He has a Ph.D. in what? 11 A I believe it's 12 pharmacology, but that may not be correct. 13 MR. FREEMAN: That's 14 correct. 15 Q Did you talk to Doctor 16 Stark about this telex? 17 A I can't remember. 18 Q Did you talk to C.D. 19 Hardison about this telex? 20 A I think it's highly 21 unlikely. 22 Q Why? 23 A Because he's a 24 statistician and the analysis that he would have 125 1 performed would have been beyond my understanding. 2 Q Did you talk to E.M. 3 Ashbrook about this telex? 4 A I doubt it. 5 Q Why? 6 A Frankly, at the time, I 7 believe, she was a clinical research associate who 8 would have had access to the data and have been 9 involved and there would be no reason for me 10 particularly to talk to her about this telex. 11 (WEINSTEIN EXHIBIT NO. 3 MARKED FOR 12 IDENTIFICATION.) 13 Q While they are looking at 14 that, did you testify earlier that you went to 15 Germany on one or two occasions in connection with 16 this registration of Prozac in Germany? 17 A Yes. 18 Q Do you recall when your 19 first trip to Germany would have been? 20 A With respect to 21 fluoxetine? 22 Q Yes. 23 A No, I don't recall. It 24 must have been sometime around mid to late 1984, 126 1 but I can't recall specifically. 2 Q Have you had an 3 opportunity to examine Exhibit 3? 4 A Yes. 5 Q That's dated July 11, 6 1984? 7 A Yes. 8 Q A couple of weeks after 9 this June 26 telex, right? 10 A Right. 11 Q And you are the primary 12 addressee on that document, are you not? 13 A Correct. 14 Q And it is directed to you 15 by an individual by the name of Heymanns? 16 A Heymanns, yes. 17 Q And who is that? 18 A It is a person who was 19 involved in regulatory matters for our affiliate 20 in Germany. 21 Q The caption there is 22 fluoxetine answer to BGA, correct? 23 A Correct. 24 Q It says, "Professor," 127 1 blank, "(formerly with the BGA) is of the opinion 2 that it would not cause any bad impression if we 3 asked for a prolongation of the time to answer the 4 letter with questions. This is done very often, 5 also by big companies, and the reviewer does not 6 care about this. On the contrary, the BGA would 7 get the impression that we take their point 8 serious and prepare the answers very carefully. 9 So from the registration point of view there is no 10 disadvantage to ask for a prolongation until 11 October 18. However, we can wait to ask for a 12 prolongation until August 1. Regards, Heymanns," 13 correct? 14 A Correct. 15 Q Why was he sending this 16 to you? 17 A Pardon me? 18 Q Why was Mr. Heymanns -- 19 or is it Doctor Heymanns? 20 A It's a woman, and it's 21 Ms. Heymanns. 22 Q Why was Ms. Heymanns 23 sending this to you? 24 A Because, again, I had 128 1 overall responsibility for coordinating the 2 response, although not specifically answering the 3 response. 4 Q And had you sent her a 5 message earlier that you needed some more time to 6 come up with a response to the questions being 7 raised? 8 A That certainly is a 9 possibility. I don't recall a specific message to 10 her; that may well have happened. 11 Q Is that a reasonable 12 interpretation? 13 A That's a reasonable 14 interpretation. 15 Q Do you recall having a 16 sense at the time that you needed some more time 17 to respond to these issues as raised by the BGA? 18 A I don't specifically 19 recall; however, in order to analyze data, time is 20 required, and it may well have been that we asked 21 for a prolongation or desired a prolongation. 22 Q Is this your writing on 23 the top of this document? 24 A No. 129 1 Q None of it is your 2 writing? 3 A None of it is my writing. 4 Q It says CC: D. -- 5 A Argay. 6 Q Who is that? 7 A He is a person who, at 8 the time, I believe, was a marketing person or -- 9 I believe a marketing person. 10 Q It says D. Thompson, who 11 is that? 12 A I think he, at that time, 13 was in a function called new product planning, and 14 maybe Argay also was, I believe at that time, in 15 new product planning. 16 Q It says CC: W. Longo or 17 Lango; who is that? 18 A I think that is W. Lange, 19 L-A-N-G-E, Wally Lange, who was a vice president 20 also responsible for the new product planning 21 function. 22 Q Wally -- 23 A L-A-N-G-E. 24 Q And at the time he was 130 1 vice president of new product planning? 2 A I believe that's what his 3 role was at that time. He was responsible for 4 that function in the company. 5 Q Is Wally Lange or W. 6 Lange still employed by Eli Lilly and Company? 7 A No, he retired. 8 Q He was fired? 9 A He retired. 10 Q When did he retire? 11 A About three or four years 12 ago. 13 Q Is he a medical doctor? 14 A No. 15 Q He was a marketing man? 16 A Yes. 17 Q Do you recall talking 18 with Wally Lange concerning Exhibit 3? 19 A No. 20 Q At the top of the page in 21 what appears to be the same writing, is it Tobe 22 Emaly, can you tell? 23 A I can't tell. 24 Q Do you know who that is, 131 1 either by the first name or the last name? 2 A Frankly, it looks closest 3 to me to Tom Emmick, who is one of the addressees 4 on this list, but that's just my interpretation of 5 relatively uninterpretable handwriting. 6 Q There's a stamp July 12, 7 1984. 8 A Yes. 9 Q And then under that it 10 appears to say "delay OE", does it not? 11 A I can't read that 12 writing. I think that all I can tell you is that 13 the stamp is Mr. Lange's stamp because his name is 14 actually E. Walter Lange, and I assume because the 15 two letters there are E and W, it's his stamp, and 16 I can't interpret the rest of it. 17 Q Do you know what the "OE" 18 might be? 19 A No. 20 Q None of the writing is 21 yours, though? 22 A None of the writing is 23 mine. 24 132 1 (WEINSTEIN EXHIBIT NO. 4 MARKED FOR 2 IDENTIFICATION.) 3 Q Doctor Weinstein, Exhibit 4 4 is a document authored by D.E. Thompson, 5 apparently directed to E.W. Lange, dated October 6 22, 1984, correct? 7 A Correct. 8 Q And I think you 9 identified Lange earlier was a vice president in 10 marketing, new products, correct? 11 A Correct. 12 Q And you are not addressed 13 on this document, so I'm not going to belabor it 14 with you other than to ask you do you recall 15 seeing anything concerning the German package 16 insert for Prozac? 17 A For Prozac? 18 Q Well, this German package 19 insert for Fluvoxamine, which is a different 20 product, is it not? 21 A That's correct. Are you 22 asking me about Fluvoxamine or Prozac? 23 Q Have you seen this 24 document before? 133 1 A I don't recall this 2 document. 3 Q If you read this 4 document, apparently what has happened is they've 5 sent the Fluvoxamine package insert to Mr. Lange 6 for comparison or use apparently in registration 7 of fluoxetine, correct? 8 A No, that's not the way I 9 interpret this. 10 Q How do you interpret it? 11 A That Mr. Thompson 12 mentions that in the Fluvoxamine package insert in 13 Germany there is apparently a statement that side 14 effects decrease after two to three weeks and that 15 benzodiazepines can be co-prescribed, and that 16 Mr. Thompson is telling Mr. Lange that he's asked 17 the medical group to analyze our data to see 18 whether it would be possible to make similar 19 statements. 20 Q Was it? 21 A I don't know. I don't 22 recall being involved in this at all. 23 Q Well, he says in the last 24 sentence, in connection with the recommendation of 134 1 benzodiazepines being prescribed as co-medication 2 that this is also something that will be very 3 important for fluoxetine, does he not? 4 A He says that. 5 Q Do you know why the co- 6 administration of benzodiazepines would be 7 important for fluoxetine? 8 A I assume it's related to 9 some marketing issue that he was thinking about. 10 He's certainly not a scientist and I don't believe 11 he was commenting on anything scientific. 12 Q How would that have a 13 marketing import or impact? 14 A I really can't presume -- 15 being a nonmarketing person, I really can't 16 presume to understand what might have been in his 17 mind at that time. I assuming that since he was 18 director of new product planning that he was 19 looking at something from a marketing point of 20 view. 21 Q All right. 22 MR. FREEMAN: What time 23 do you want to break for lunch? 24 MR. SMITH: Any time. 135 1 MR. FREEMAN: Go ahead 2 for fifteen more minutes, if you want to. 3 MR. SMITH: Okay. 4 (WEINSTEIN EXHIBIT NO. 5 MARKED FOR 5 IDENTIFICATION.) 6 Q You don't have to read 7 the entire package insert, Doctor Weinstein, 8 except for the side effects listed on Page 2 and 9 the next to the last paragraph of Page 3. 10 A The next to the last 11 paragraph on Page 3? 12 Q It starts "for patients 13 suffering from agitation". 14 A Okay. 15 Q Exhibit 5 is apparently a 16 document sent by Heymanns in Bad Homburg to Doctor 17 Wernicke in Indianapolis on October 31, 1984, 18 correct? 19 A Correct. 20 Q It is transmitting the 21 fluoxetine package insert for Germany, correct? 22 A Well, the one that was 23 submitted to the BGA. 24 Q All right, but it was -- 136 1 yes, it was submitted to the BGA and was intended 2 to be the package insert for patients in Germany, 3 correct? 4 A Yes; if the BGA approved 5 it, yes. 6 MR. FREEMAN: You don't 7 mean to say patients, but doctors in Germany? 8 MR. SMITH: That's what 9 I'm going to get to. 10 MR. FREEMAN: Okay. 11 Q (BY MR. SMITH) What is 12 your understanding in connection with what is 13 actually being transmitted; is this a package 14 insert or is this prescribing information for 15 doctors, or is this something that goes to 16 patients? 17 A My understanding is that 18 in Germany there are really two types of product 19 literature; one that goes to patients, and my very 20 brief look at this would suggest that that is what 21 this is, and another that is much more extensive 22 that is published in a book that goes to all 23 physicians in the country that has much more 24 detail and is expressed in terms which are more 137 1 medical than the terms in this literature. 2 Q And you think this is 3 patient prescribing information or information 4 that the patient gets? 5 A My interpretation of this 6 is that in view of the words that are used, it is 7 more likely a patient piece of information than a 8 physician piece of information. 9 Q Why is it that the 10 patients get information in Germany? 11 A That is the requirement 12 of the German government. 13 Q Is there such a 14 requirement in the United States? 15 A No. 16 Q Do you know why that is? 17 A Different governments 18 have different regulations and I'm not aware of 19 why, in this particular instance, there is a 20 difference between these countries, but there are 21 many countries in which there is no package 22 information for patients, not only the United 23 States. 24 Q Are their other countries 138 1 in addition to Germany where patients get 2 information concerning the properties of the drug? 3 A Yes. 4 Q Give me the names of some 5 others at least. 6 A I'm aware that at this 7 time, in 1984, there were other European 8 countries, I believe among them Belgium, Spain and 9 perhaps France, in which there were -- there was 10 information provided to patients. I'm also aware 11 of the fact that in countries such as the UK, 12 there were no patient prescribing information 13 leaflets. 14 Q But in those countries 15 where patient information leaflets were required, 16 they were indeed required by law? 17 A Correct. 18 Q And a pharmaceutical 19 manufacturer was required to submit for approval 20 to the foreign regulatory body the specific 21 language of the information that was going to the 22 patient? 23 A I'm certain that that was 24 the case in Germany. I really don't have enough 139 1 knowledge of the other countries to comment. 2 Q Do you, as a medical 3 doctor, have any objection from a medical 4 standpoint to patients getting information 5 concerning drugs they take? 6 A No. 7 Q Page 3 of the proposed 8 information that patients in Germany would get 9 states that, quote, "For patients suffering from 10 agitation or marked sleep disturbances, the 11 concomitant administration of a sedating or 12 sleep-inducing drug at the beginning of treatment 13 may be recommended due to the non-sedating effect 14 of Fluctin," correct? 15 A Correct. 16 Q And Fluctin is Prozac, 17 isn't it? 18 A Correct. 19 Q Do you have any 20 objections to patients in Germany getting the 21 information that I quoted on Page 3, as a medical 22 doctor? 23 A No. 24 Q From a medical 140 1 standpoint, there is no difference in individuals 2 suffering from depression in Germany and 3 individuals suffering from depression in the 4 United States, is there? 5 A Not that I'm aware of. 6 Q Do you know anything 7 about German individuals that would require that 8 they be given sedatives or that sedatives are 9 particularly appropriate for Germans as opposed to 10 other individuals of other nationalities? 11 A No. 12 (LUNCH BREAK TAKEN.) 13 (WEINSTEIN EXHIBIT NO. 6 MARKED FOR 14 IDENTIFICATION.) 15 Q (BY MR. SMITH) Doctor 16 Weinstein, can you identify Exhibit 6 -- or let me 17 speed it up -- as being a telex dated January 29, 18 1985, directed to you as a principal addressee, 19 from Doctors Weber, Chandler and Mayr in Germany? 20 A Chandler and Mayr are not 21 doctors, but, yes. 22 Q The subject of the 23 document indicates that it's fluoxetine 24 registration, correct? 141 1 A Yes. 2 Q And they notify you that 3 they have unofficially received confirmation that 4 fluoxetine was discussed by Commission A at the 5 BGA on January 21, correct? 6 A Correct. 7 Q It seems that two major 8 concerns seem to be the reason that the 9 registration was not accepted, is that what it 10 says there? 11 A Correct. 12 Q Did you know before you 13 received this document that the BGA or Commission 14 A had not accepted the application or registration 15 of Prozac in Germany at that time? 16 A I can't recall whether I 17 knew before this telex or after. 18 Q Do you recall getting 19 this telex? 20 A Vaguely recall getting 21 this telex. 22 Q This telex indicates that 23 two major concerns seem to be the reason that the 24 registration was not accepted. The first is 142 1 efficacy questions, the second is suicidal risk, 2 correct? 3 A Correct. 4 Q Then it suggests various 5 things to do in connection with an action plan on 6 Prozac, does it not? 7 A Yes. 8 Q Now, do you recall doing 9 anything in connection with this document? 10 A I don't recall 11 specifically what I did and the response to this 12 document, no. 13 Q Who is E.R. Roberts, the 14 other principal addressee? 15 A A former -- I'm not sure 16 of his title, Executive Vice President, I believe, 17 of Lilly International. 18 Q Did you speak with 19 Mr. Roberts concerning this problem? 20 A I don't recall. 21 Q Is this your writing on 22 the top of the page? 23 A No. 24 Q This is a document that 143 1 was produced in connection with your deposition 2 supposedly from your files, Doctor. 3 MR. MYERS: That wouldn't 4 be right, Paul. Let me just clarify. The 5 documents that have been produced are not only 6 from the files of the witness, but if somebody 7 else had a document where he's the author or 8 recipient, it might also be produced, so not 9 necessarily from his file, and that's the way 10 things have been produced, I think, since we 11 started this exercise. 12 MR. SMITH: All right. 13 MS. ZETTLER: Let me 14 clarify, too, but they are produced as documents 15 that have been authored by Doctor Weinstein, where 16 he was a recipient or may have -- 17 MR. MYERS: Author or 18 recipient, yes, in addition to what may or may not 19 be in his file, that's right. 20 Q (BY MR. SMITH) Do you 21 have any explanation for the notation in the top 22 right-hand side of the page "inside 23 communication"? 24 A No. 144 1 Q Do you have any 2 explanation for, under that, outside, two dashes 3 which must be communication also? 4 A No. 5 Q Under that there is the 6 notation security -- is that analyst? 7 A I believe so. 8 Q Would that be a security 9 analyst like anti-terrorist activity, or would 10 that be like a stockbroker activity? 11 A I can't interpret; I 12 would assume that it is a stockbroker. 13 Q Do you recognize those 14 initials under that notation? 15 A I think it says 16 et cetera, E-T-C, period. 17 Q That's what I thought it 18 said at first, then I thought, well, it might be 19 somebody's initials. Is this when you went to 20 Germany, to take care of this problem, when you 21 got this? 22 A I don't recall 23 specifically, it may have been related to one of 24 my trips to Germany. 145 1 Q The reason I ask is it 2 says, the fourth line from the bottom, meeting 3 scheduled on Monday afternoon, February 4th at 4 1:00 PM, do you see that? 5 A It says that. 6 Q Do you have a 7 recollection of whether that meeting was in 8 Germany or in Indianapolis? 9 A I'm assuming, based on 10 what it says, that it was in Germany, since it 11 says with our clinical expert, and this is coming 12 from Germany. 13 Q Do you remember meeting 14 in Germany with a clinical expert in the winter of 15 1984? 16 A Not specifically; I may 17 have. I was in Germany on a number of occasions 18 for a variety of reasons, many of them not related 19 to this product at all. 20 Q Do you remember meeting 21 with experts at any time in connection with the 22 issue of registration of Prozac and the problems 23 of suicide risk that were raised by the German 24 government? 146 1 A My only recollection is 2 meetings that I attended that were held at the BGA 3 between members of the Lilly staff and the BGA. I 4 do not recall being at any meetings that were held 5 with outside experts and Lilly personnel. 6 Q Do you recall that there 7 was consultation called in by Lilly of outside 8 experts on this issue, of registering Prozac in 9 Germany and the problems presented by the suicide 10 risk as seen by the German government? 11 A I remember that -- my 12 supposition based on this telex is that there 13 would have been meetings with outside experts 14 about the fact that the registration was not 15 accepted. 16 Q But you don't recall any 17 meetings that you attended where there were 18 outside experts? 19 A No. 20 Q Do you recall seeing any 21 reports from any outside experts in connection 22 with this problem? 23 A I may have, but I don't 24 specifically recall them. 147 1 Q Did you talk with any key 2 opinion leaders on the BGA? 3 A I'm sorry, can you 4 explain that? Opinion leaders are not part of the 5 BGA. 6 Q The reason I ask is the 7 last bullet point on Page 1 says, "Immediate 8 follow-up on all key opinion leaders on the BGA 9 Commission for selected visitation next week." 10 A Let me help you 11 understand how the BGA works. The commission is a 12 group of outside people who scientifically analyze 13 submissions that are made, so everybody on 14 Commission A is not an employee of the BGA, but is 15 an outside academic person. The BGA is a more 16 government-related agency, it is not at all like 17 the FDA. They do not have internal expertise in 18 most scientific areas, so they rely on outside 19 groups. I did not speak to anybody on Commission 20 A. 21 Q Do you think that's good 22 or bad that a governmental agency making a 23 decision to approve or disapprove of a particular 24 product, pharmaceutical product, would call in 148 1 outside experts from a variety of disciplines to 2 examine particular issues in connection with a 3 particular drug? 4 A I think it's neither good 5 nor bad; I think its perfectly acceptable and 6 perfectly reasonable. 7 Q The reason it's 8 reasonable, isn't it because that governmental 9 entity will get input from individuals that don't 10 have a direct tie with the government or with the 11 particular industry, correct? 12 A That is correct. 13 Q And is it your judgment, 14 from observing the workings of the German 15 government, that this commission system that they 16 have is reasonably efficient in the manner in 17 which it does business? 18 A It is no more or less 19 efficient than other government regulatory 20 agencies. 21 Q Would you say it's as 22 efficient as the United States Food and Drug 23 Administration in examining safety and efficacy in 24 connection with pharmaceutical products? 149 1 A Yes. 2 Q All right. Did you visit 3 with key opinion leaders on Commission A? 4 A No. 5 Q Did anybody from Lilly do 6 that? 7 A I do not know. This 8 telex mentions plans to visit with them, but I do 9 not know if, in fact, those plans were realized. 10 Q Did you have, at the 11 time -- and when I say you, anybody at Lilly which 12 you are aware of -- have a list of individuals who 13 were on Commission A? 14 A I don't know. I 15 certainly did not. 16 Q In this commission system 17 employed by the German government, would members 18 of the commission be different with respect to the 19 nature of the particular drug under investigation? 20 A As far as I understand 21 the system, the answer to that question is no, 22 that there would be a group of experts in science 23 and medicine representing a variety of areas of 24 specialty that constituted Commission A, that they 150 1 would investigate drugs for psychiatric disorders, 2 for cancer, for heart disease, and other 3 conditions. 4 Q But in that situation, 5 the commission would have supposedly psychiatrists 6 or psychopharmacologists or neurologists or 7 individuals who would be familiar with the mode of 8 action of a psychotropic drug such as Prozac? 9 A I presume that's correct. 10 Q Then they might also have 11 microbiologists or immunologists to examine 12 antibiotics or things of that nature? 13 A Most likely. 14 Q And when the drug is a 15 psychotropic medication, is it your experience 16 that the members of the commission who were not 17 directly concerned with that particular aspect or 18 that particular specialty, look to, say, the 19 psychiatrist for psychotropic medication for 20 guidance? 21 A I really have no 22 experience. One would assume that that would be 23 the case, but I really do not know how judgments 24 are made. 151 1 Q The reason I ask that is 2 because it says immediate follow-up on all key 3 opinion leaders on the BGA commission, and I 4 would -- I was wondering if the key opinion 5 leaders in a psychotropic medication would be 6 different key opinion leaders than there would be 7 if there was an anticancer medication under 8 consideration? 9 A One would presume so. 10 Q But you never talked to 11 any members of the commission? 12 A No. 13 Q Do you know whether or 14 not any of the plans were done? 15 A You mean the plans that 16 are -- 17 Q That are outlined; the 18 meeting of February 4, the follow-up on key 19 opinion leaders, expedition of local German Prozac 20 trials. 21 A I don't know specifically 22 how these were followed up, no. 23 Q Whose responsibility 24 would it have been, Doctor, to see that that was 152 1 done? 2 A The members of the 3 medical group primarily in Lilly Germany. 4 Q In Lilly Germany? 5 A That's correct. 6 Q Who in Indianapolis would 7 have been responsible for that? 8 A This would not have been 9 an Indianapolis responsibility. There were 10 questions raised apparently by the BGA, there was 11 an action plan suggested by Lilly Germany, and it 12 was therefore the responsibility of Lilly Germany, 13 if they felt it appropriate, to carry out those 14 actions. 15 Q But you went over there, 16 didn't you? 17 A I do not recall that I 18 specifically went over there on this event; I 19 recall that around this time, I may well have been 20 in Germany. I don't recall responding 21 specifically to this telex by going to Germany. 22 In fact, since all of the conversation with these 23 individuals would have been in German, which I do 24 not speak, it would not have been a terribly good 153 1 expenditure of my time or the company's money to 2 go to those meetings. 3 Q Was there anybody there 4 in Indianapolis, say Doctor Zerbe, Wernicke, Leigh 5 Thompson, that was conversant in and fluent in 6 German? 7 A Yes, I believe Doctor 8 Warnicke is fluent in German. 9 Q Did you say you did talk 10 and appear at the BGA in connection with the 11 registration of Prozac? 12 A Yes. 13 Q When was that? 14 A I don't recall 15 specifically. I believe it was in 1985 at some 16 time. 17 Q Was it before you got the 18 intent to reject letter that caused Lilly to 19 withdraw their application for a period of time 20 and then later resubmit it? 21 A I don't really recall 22 that. It might have been possibly in the interim 23 between this message and the formal writing of 24 that letter, but it may not have been; I don't 154 1 recall the specific timing. 2 Q We've got that letter and 3 let's go ahead and talk about that. It might help 4 you. 5 (WEINSTEIN EXHIBIT NO. 7 MARKED FOR 6 IDENTIFICATION.) 7 A Okay. 8 Q Exhibit No. 7 is two 9 documents stapled together. The first two pages 10 are -- actually it's one document with a telecopy 11 message that encloses the official notification 12 from the BGA, correct? 13 A Encloses a translation of 14 that official document. 15 Q It's dated February 27, 16 1985, that is the telecopy message, isn't it? 17 A Yes. 18 Q And the actual action of 19 the German government is dated February 26, 1985? 20 A Yes. 21 Q It is a message that is 22 directed to you in Indianapolis? 23 A Correct. 24 Q And the only other 155 1 individual in Indianapolis to receive a copy of 2 this document is E.R. Roberts, correct? 3 A Correct. 4 Q And he is again? 5 A He is a former, I 6 believe, Executive Vice President of Lilly 7 International. 8 Q Is he a medical doctor? 9 A No. 10 Q The document says, 11 "You'll find attached the BGA response letter." 12 "The letter is indeed an intention of rejection 13 and not a rejection itself, and we have three 14 months in which to respond," correct? 15 A Correct. 16 Q The document goes on to 17 say, "The contents of the letter is mainly 18 consistent with objections which we have heard 19 before," correct? 20 A Correct. 21 Q Now, when you received 22 this letter, did you recall objections that had 23 been received before? 24 A I'm not sure what this 156 1 refers to. 2 Q Well, we know, by virtue 3 of the documents that I've handed you, 4 specifically Exhibit 6, that you had had advanced 5 warning a month prior to that, that the German 6 government considered suicidal risk, or the 7 Commission considered suicidal risk as a real 8 problem in getting this product registered in 9 Germany, didn't it? 10 A We had heard a month 11 earlier that there were two concerns of the German 12 government, one was efficacy and one was suicide. 13 Q And it again refers to 14 these problems in the February 27 telecopy 15 message, correct? 16 A Correct. 17 Q And again the problem of 18 suicide is mentioned, is it not, on the bottom of 19 the page? 20 A Yes. 21 Q As Item 4, correct? 22 A Correct. 23 Q In the paragraph above 24 that there is the following language, quote: "The 157 1 letter from the BGA is nearly identical with the 2 opinions of Professor Herrmann, whom Doctor H.J. 3 Weber and S. Heymanns visited a day before. 4 According to his opinion the following problems 5 exist," and he lists No. 4, suicide, correct? 6 A Correct. 7 Q Had you met with Doctor 8 Herrmann at all? 9 A Not that I recall. 10 Q Had you ever heard of 11 Doctor Herrmann? 12 A I may have. I don't 13 specifically recall, but I may well have heard of 14 him. 15 Q Have you seen any 16 document from Professor or Doctor Herrmann? 17 A I'm sorry, seen any 18 documents? 19 Q Yes. 20 A Not that I'm aware of. 21 Q The last paragraph of the 22 telecopy message says, "I would like to get your 23 comment and specific direction to which points are 24 necessary to follow up for clarification. To get 158 1 a better understanding we will be contacting 2 during the next few days Straeter, the BGA (your 3 questions) and other opinion leaders prior to an 4 Indianapolis meeting. Your list of priorities 5 would assist our efforts for next weeks 6 activities," correct? 7 A Correct. 8 Q Now, had you sent a list 9 of priorities or did you send a list of priorities 10 to Doctor Weber or anybody in Germany? 11 A Are you asking in 12 response to this? 13 Q Yes. 14 A I really don't recall. I 15 must have, but if I did, I don't recall the 16 document. 17 Q Well, this was bad news, 18 wasn't it, Doctor Weinstein? 19 A Yes. 20 Q Germany has a large 21 population? 22 A It has a sizeable 23 population, yes. 24 Q It presents a sizeable 159 1 market for this product, does it not? 2 A I would assume so. 3 Again, I'm not a marketeer, but -- 4 Q Okay, as a physician, 5 from a humanitarian standpoint, if the product 6 were relieving depression, Germany presented a 7 substantial number of potential patients who had 8 depressive illnesses that could be benefited by 9 Prozac, correct? 10 A Correct. 11 Q So it presented a problem 12 from a medical standpoint, too, didn't it? 13 A If that's your 14 interpretation of medical, yes, I would agree. 15 Q Well, isn't depression a 16 medical problem? 17 A Yes. 18 Q Isn't antidepressant 19 treatment an acceptable medical treatment for a 20 known and established psychiatric condition? 21 A Yes. 22 Q But you don't recall 23 anything you did in connection with giving these 24 people in Germany some direction on what they 160 1 should do to get this product registered in 2 Germany? 3 A I don't remember 4 specifically how I responded to this telecopy 5 message, no, I don't. 6 Q Do you recall generally 7 how you responded to this telecopy message? 8 MR. FREEMAN: By 9 telephone or memo or whatever? 10 Q That and what your 11 response was, in general. 12 A In general, the response 13 was to attempt to either analyze data that was 14 currently available at the time, or develop data 15 based on new studies that would deal with the 16 questions that the German government had raised. 17 Q Was there some data in 18 existence at the time that hadn't been analyzed? 19 A I'm not aware of that; 20 but as occasionally happens, different types of 21 analyses are required to answer a variety of 22 governmental questions. 23 Q Well, was your 24 application for registration incomplete, in your 161 1 judgment? 2 A No. 3 Q Or in the judgment of the 4 BGA? 5 A No, the judgment of the 6 BGA was that there are other questions that the 7 initial submission had not answered according to 8 their requirements. 9 Q Well, let's look at what 10 the BGA specifically said in connection with the 11 application of Prozac, Fluctin, for treatment of 12 depression for individuals in Germany, and it's 13 attached to Exhibit 7, is it not? 14 A Correct. 15 Q And it says, "Ladies and 16 Gentlemen, after the commission according to 25 17 par, 6 AMG was heard, we intend to refuse the 18 registration of the above mentioned drugs for the 19 following reasons," correct? 20 A Correct. 21 Q And then it goes on and 22 enumerates one and a quarter page of reasons that 23 they intended to refuse the registration of Prozac 24 in Germany, correct? 162 1 A Correct. 2 Q Number one, it says the 3 drugs are not sufficiently tested according to the 4 secured state of scientific knowledge, correct? 5 A That's what it says, 6 correct. 7 Q It also says Prozac, 8 fluoxetine's profile of action was insufficiently 9 characterized, correct? 10 A Correct. 11 Q There were methodological 12 problems at the carrying out of the studies, 13 paren, too short washout period, concomitant 14 treatment with other psychotropic drugs, and 15 choice of control drugs, correct? 16 A Correct. 17 Q Do you have any idea what 18 kind of control drugs were being used in the 19 closed Prozac clinical trials? 20 A I don't know specifically 21 which control drugs they're referring to in this 22 letter. 23 Q The BGA had information 24 from the clinical trials that were done in the 163 1 United States, did they not? 2 A Correct. 3 Q The BGA also had whatever 4 information was available from clinical trials on 5 Prozac done outside the United States, didn't 6 they? 7 A Correct. 8 Q Do you know of any 9 differences, in February of 1985, of the documents 10 and data that was available to the BGA in Germany 11 and the United States Food and Drug Administration 12 in the United States? 13 A No. 14 Q According to what you 15 know, should it have been exactly the same? 16 A Yes. 17 Q The same pivotal studies 18 that were submitted to the Food and Drug 19 Administration in the United States should have 20 been submitted to the BGA in Germany? 21 A Were submitted to the BGA 22 in Germany. 23 Q In fact, were submitted, 24 correct? 164 1 A Correct. 2 Q And their judgment 3 concerning those studies was that the drugs had 4 not been sufficiently tested and that the profile 5 of action was insufficiently characterized, 6 correct? 7 A That's their judgment. 8 Q Huh? 9 A That is their judgment. 10 Q Additionally, they go on 11 with additional judgments, that the completed 12 studies do not allow a judgment on efficacy and 13 safety in long-term use, correct? 14 A Correct. 15 Q Also that document states 16 that that data submitted by Lilly on Prozac 17 concerning the clinical trials is according to -- 18 indicated that for the drug concerned -- that is 19 Prozac, isn't it? 20 A Yes. 21 Q There is, according to 22 their specific profile of adverse effects, the 23 justified suspicion that they have unacceptable 24 damaging effects, correct? 165 1 A Correct. 2 Q In other words, they're 3 saying that there are too many adverse effects and 4 that this caused a justified suspicion that those 5 adverse effects would have unacceptable damaging 6 effects, does it not? 7 A No, it does not say there 8 are too many adverse effects. 9 Q Well, the adverse 10 effects, as per the specific profile, or the 11 specific profile of adverse effects, had an 12 unacceptable damaging effect, correct? 13 A The statement is that 14 they suspect that it might have an unacceptable 15 damaging effect; the suspicion is raised, they do 16 not confirm that that -- 17 Q Well, isn't that their 18 job? 19 MR. MYERS: Let him 20 finish, Paul. 21 Q Isn't that their job to 22 confirm suspicions? 23 A I'm not in a position to 24 tell the BGA what their job is. 166 1 Q Well, isn't that your 2 understanding of what their job is? 3 A Their job is to monitor 4 and assess the efficacy and the safety of 5 pharmaceutical agents. They have said that they 6 suspect that there might be unacceptable damaging 7 effects. 8 Q They go on to say the 9 following, also, don't they, that the use of the 10 preparations seems objectionable, as the increase 11 in agitating effect occurs earlier than the mood 12 elevating effect and therefore an increased risk 13 of suicide exists, correct? 14 A That's what they say, 15 correct. 16 Q They don't talk about 17 suspicion there, do they, Doctor? 18 A No. 19 Q They go on to say that, 20 quote, "During treatment with the drugs some 21 symptoms of the underlying disease (anxiety, 22 insomnia, agitation) increase, which as adverse 23 effects exceeds those which are considered 24 acceptable by medical standards," correct? 167 1 A Correct. 2 Q That is in effect saying, 3 isn't it, Doctor, that the core symptoms of 4 depression, anxiety, insomnia, and agitation, the 5 adverse effects seen -- these adverse effects seen 6 by the data submitted by Lilly to the BGA exceed 7 what you would expect to see that would be 8 considered acceptable by medical standards? 9 A That is the BGA's 10 interpretation of the data, correct. 11 Q Do you have any evidence, 12 have you seen any evidence or heard of any 13 evidence whatsoever, Doctor Weinstein, that would 14 scientifically refute the judgment made by the BGA 15 in connection with the data that they reviewed? 16 A I have seen no scientific 17 data that would confirm the judgment, which is 18 unique to the BGA, that they have made concerning 19 this data. 20 Q That's not what I asked 21 you. Have you seen any scientific data that would 22 refute the scientific judgment made by the BGA in 23 connection with the issues presented here? 24 A I personally have not 168 1 seen data; I am aware that such data has been 2 presented by others. 3 Q Where is that data and 4 what is that data? 5 A Among others, that data 6 would appear in Doctor Beasley's paper in the 7 British Medical Journal. 8 Q We can go over that 9 again, but certainly that information presented by 10 Doctor Beasley in the New England Medical Journal 11 had to do with a limited clinical trial 12 experience, didn't it? 13 A It had to do with a 14 clinical trial experience, and by the way, it was 15 the British Medical Journal. 16 Q What did I say? 17 A New England Journal of 18 Medicine. 19 Q It was submitted to the 20 New England Medical Journal, but rejected by them, 21 wasn't it? 22 A Yes. 23 Q And it was accepted for 24 publication by the British Medical Journal? 169 1 A Correct. 2 Q And the data reported 3 there is limited data, isn't it? 4 A It is the clinical -- the 5 comparative clinical trial data that was generated 6 in the US. 7 Q Which is limited? 8 A It is not all of the data 9 that was available. 10 Q And the BGA had more data 11 available to review than is reported by Doctor 12 Beasley in his article, his, quote, meta analysis, 13 end quote, of suicidality raised during the Prozac 14 clinical trials, didn't they? 15 A I believe that's correct. 16 Q Do you know of any other 17 scientific data that would refute the conclusions 18 made by the BGA in Germany listed in Exhibit 6? 19 MR. FREEMAN: Objection, 20 that question has been asked and answered. The 21 Doctor has said that every other agency that had 22 reviewed the same data interpreted it differently, 23 came to a different conclusion than the BGA. 24 MR. SMITH: He said the 170 1 Beasley article, in addition to others. I just 2 simply want to know what other -- 3 MR. FREEMAN: He earlier 4 had said that the other agencies that had reviewed 5 the same data came to a different conclusion. 6 That refutes it in itself. 7 Q (BY MR. SMITH) Do you 8 know of any other scientific data that refutes 9 this? 10 A No, I don't know of any 11 specific scientific data. 12 Q Tell me about your 13 meeting with the BGA, whenever it was that it 14 occurred. 15 A The limited memory I have 16 of that meeting is that the meeting was managed, 17 if you will, led on the Lilly side by Doctor 18 Weber, and that there was a discussion of the 19 questions that the BGA had raised and what we 20 might do in terms of data analysis or the 21 institution of additional studies to answer those 22 questions. I have to tell you again that the 23 meeting was held in German, that I was getting 24 translation while the meeting was going on, and 171 1 that my ability to participate actively in the 2 meeting was severely limited. 3 Q Was Doctor Wernicke 4 there? 5 A I don't believe so, but I 6 don't specifically recall. 7 MR. FREEMAN: Doctor who 8 did you say? 9 MR. SMITH: Wernicke. 10 Q (BY MR. SMITH) I thought 11 he might be there since we see later on that he 12 transmitted a lot of suicide data to Germany and 13 since you told us that he speaks German. See if 14 you can think whether you recall Doctor Wernicke 15 being present at the meeting. 16 A I do not recall him being 17 present at the meeting. 18 Q Do you think you would 19 have recalled had he been present? 20 A Possibly not; I just 21 don't recall. 22 Q Do you remember if 23 anybody went with you from Indianapolis? 24 A I don't recall. It is 172 1 possible, but I don't have a specific recollection 2 of who would have gone with me at the time. 3 Again, the meeting was conducted in German and 4 since most of us are not fluent in German, it 5 would be unlikely that we would have sent very 6 many people. 7 Q Can you give us any 8 judgment of whether or not the meeting was before 9 or after this intent to reject letter was issued? 10 A No, honestly I can't. It 11 could have been before and it could have been 12 after, and I just don't remember when it was. 13 Q See, the importance of 14 that would be that if it were before, you all had 15 made -- when I say you all, that's the way we 16 Texans would say you people from Indianapolis and 17 you people from Lilly, would have made your 18 argument to the BGA concerning the issues raised 19 by the BGA a month earlier, and apparently they 20 were not successful by virtue of the intent to 21 reject letter. That's the reason I'm -- 22 A As I recall, the purpose 23 of any meeting that I was involved with, with the 24 BGA, was to gain more information and to better 173 1 understand what their questions were, rather than 2 to try to convince them to adopt some view other 3 than the one that they were going to adopt. 4 Q Well, there wasn't a 5 situation there where Lilly was taking the 6 position that you just haven't seen all the data, 7 were they? 8 A No, I think if you look 9 at the specifics in this message, there are things 10 that clearly we did not have, particularly studies 11 in Germany, certain inpatient studies that the BGA 12 felt very strongly about, that were going to 13 require us to develop new studies. 14 Q Why would you have 15 submitted the application if you had known that 16 you didn't have the right studies that would be 17 necessary to support an application? 18 A Clearly, we didn't know 19 that we didn't have the right studies. 20 Q Isn't there some type of 21 guidelines or some type of instruction that is 22 available for a pharmaceutical firm to know what 23 is going to be necessary? 24 A In many fields, there are 174 1 now guidelines. In the early '80s, as far as I am 2 aware, there were no European guidelines for the 3 development of antidepressant medications. 4 Q Well, could it be said, 5 Doctor Weinstein, that when this application was 6 submitted prior to February 25, 1985, Lilly at 7 least thought that they had enough data to support 8 the application? 9 A That's correct. 10 Q This was, in fact, the 11 same data that was pending before the United 12 States Food and Drug Administration, wasn't it? 13 MR. FREEMAN: Asked and 14 answered. He's already answered that twice and 15 said yes. Say yes one more time and that's the 16 last time we're going to go over that. 17 A Yes. 18 Q Anything else that you 19 recall about the meeting with the BGA? 20 A No. 21 Q And I hate to beat this 22 to death, but I think it's relatively important: 23 Can we say that this meeting that you had with the 24 BGA would have been either shortly before or 175 1 shortly after February 25, when this intent to 2 reject letter came down? I just don't want to 3 have it come up at trial that this meeting was a 4 year earlier or a year later. 5 MR. FREEMAN: You're 6 going to have to ask that of Doctor Weber, I would 7 imagine. If he doesn't know, he doesn't know. 8 MR. SMITH: See, I won't 9 be able to ask Doctor Weber that until September, 10 and I can't wait that long, Joe. 11 A My recollection is that 12 it was shortly after or shortly before the letter. 13 Q All right. And I'll 14 grant you some leeway on that, then. I hate to 15 press you that hard. But I don't hate it that 16 bad, not bad enough to stop. 17 (WEINSTEIN EXHIBIT NO. 8 MARKED FOR 18 IDENTIFICATION.) 19 Q Doctor, Exhibit 8 is 20 apparently a Report on Fluoxetine Working Session 21 of April 29 and 30, authored by Doctor Johanna 22 Schenk, is that correct? 23 A Correct. 24 Q There's a date of April 176 1 3, 1985 on the top left-hand side of the page, and 2 then there's an addressee list there that has 3 under it a date of April 2nd, '85, do you see 4 that? 5 A Yes. 6 Q But the meeting itself 7 apparently occurred on April 29th and 30th, 8 correct? 9 A That's what it says. I 10 suspect that's incorrect. 11 Q Or I believe Doctor Zerbe 12 indicated that there might have been a situation 13 where accidently or inadvertently something was 14 stapled to the top of this document and then 15 Xeroxed, where we're actually seeing the top of 16 one document and the bottom of another document. 17 A That's certainly 18 possible. The other possibility is that it really 19 was March 29th and 30th of 1985 that the meeting 20 was held. 21 Q Uh-huh. Had you seen 22 errors of that kind with your German affiliates, 23 where they occasionally get dates transposed by 24 some secretary? 177 1 A No. 2 Q I'm not implying anything 3 bad about that. 4 A No, I hadn't. I'm just 5 giving you another alternative answer to Doctor 6 Zerbe's explanation. 7 Q This document does have 8 the word Wally written on it, doesn't it? 9 A That's correct. 10 Q And you assume that's 11 Mr. Lange? 12 A Correct. 13 Q In marketing? 14 A Correct. 15 Q But you don't recognize 16 that writing, do you? 17 A No. 18 Q It's not your writing? 19 A It's not my writing. 20 Q Do you recall seeing this 21 document -- receiving this document? 22 A I don't recall 23 specifically receiving this document, but since it 24 was faxed to me, I'm sure I must have received it 178 1 and read it. 2 Q It indicates that there 3 was a meeting in Germany, Bad Homburg, and that 4 the purpose or objective of the meeting was to 5 make an expert, a professor, I think it says later 6 on in here, Herrmann, familiar with the fluoxetine 7 data so that he would be in a better position to 8 give advice as a consultant to the company on the 9 registration of Prozac in Germany, correct? 10 A Correct. 11 Q There was some data 12 reviewed by these individuals, and it was the 13 original documentation submitted March 1, 1984, 14 correct? 15 A Correct. 16 Q Do you have any idea what 17 specifically that would be, Doctor Weinstein? 18 A No. I assume that since 19 the US NDA was submitted in the latter part of 20 1983, that in fact this is the same data that was 21 submitted to the US government. 22 Q And do you know what the 23 pool study, fluoxetine versus imipramine versus 24 placebo, Protocol No. 27, submitted October 179 1 26, '84, is? 2 A No, I assume that is one 3 of the -- that is obviously one of the studies 4 that we performed, but I'm not familiar with the 5 specific protocol. 6 Q I'll tell you that the 7 evidence thus far has established that Protocol 8 No. 27 was a comparator/placebo control trial that 9 was submitted as a pivotal study to the United 10 States Food and Drug Administration, okay? 11 A (WITNESS MOVES HEAD UP 12 AND DOWN.) 13 Q Does that help you at 14 all? 15 A I accept your 16 explanation. 17 Q Turn with me to Page 2 -- 18 well, at the bottom of Page 1 it says that 19 Professor -- I guess it's Herrmann -- left an 20 opinion of twenty-one typewritten pages, and then 21 it goes on to summarize the points on Page 2 and 3 22 of this twenty-one typewritten page opinion, does 23 it not? 24 A Yes. 180 1 Q Have you ever seen the 2 twenty-one typewritten page opinion that is 3 summarized in Exhibit 8? 4 A I don't recall. I think 5 it's highly unlikely that I would have seen it, 6 again, because it's probably written in German, 7 and I wouldn't have understood it. 8 Q What generally would 9 happen when -- I notice this is written in 10 English, and it's something in connection with 11 something that occurred in Germany, by Germans, 12 authored by Germans, correct? 13 A Sent to people who speak 14 English. 15 Q Sent to people who speak 16 English. Did they translate this in Germany, was 17 it translated in Indianapolis? Generally, how did 18 you get the language barrier crossed? 19 A This would have been 20 translated by someone at Lilly Germany. 21 Q Doctor Weber speaks 22 English? 23 A Yes. 24 Q Fluent in English? 181 1 A Yes. 2 Q Do you know if Doctor 3 Schenk speaks English? 4 A Yes, she does. 5 Q And you say she's no 6 longer with Lilly? 7 A No. 8 Q Do you know where she is? 9 A I have not heard for a 10 number of years. She was working, I believe, for 11 Bristol Myers in Germany after she left Lilly, but 12 I'm not sure where she is employed now. 13 Q Was it your understanding 14 that she was a German citizen? 15 A She is a German citizen. 16 Q Under Safety on Page 2, 17 apparently this expert consultant hired by Lilly 18 to assist them in submitting Prozac to the German 19 regulatory authorities, states, quote, "Still not 20 resolved is the fact that suicide attempts have 21 been observed more frequently on fluoxetine as 22 compared to imipramine (only epidemiologic data or 23 literature on other antidepressants may help to 24 identifying whether it happened by chance that 182 1 incidence of suicide attempt was abnormally high 2 on fluoxetine or abnormally low under 3 comparators)," correct? 4 A I would disagree with 5 your characterization; that is not what the expert 6 said. That is a summary by our people of their 7 interpretation of what the expert said, but those 8 are not his words. 9 Q Have you ever seen those 10 words? 11 A No. 12 Q Is it your testimony here 13 that what was reported in the summary by -- when 14 you say our people, you mean somebody at Lilly in 15 Germany? 16 A Correct. 17 Q Could be inaccurate? 18 A No, I'm merely saying 19 that your statement was, I believe, the expert 20 stated, and I am pointing out that this is a 21 statement in which the essential points are 22 summarized as follows. 23 Q Okay. 24 A These are not the words 183 1 of the expert, it's not -- 2 Q But do you have any 3 reason to believe that in preparing this summary 4 that Doctor Schenk had inaccurately or 5 incompletely summarized the opinions of Doctor 6 Herrmann? 7 A No. 8 Q Have you known her to be 9 sloppy in any of her work -- 10 A No. 11 Q -- while she was at 12 Lilly? 13 A No. 14 Q Was she conscientious as 15 far as you're concerned? 16 A Very conscientious. 17 Q Was she a good Lilly 18 employee? 19 A As far as I'm concerned. 20 Q Was she a pro-Lilly 21 employee? 22 A Help me understand what 23 pro-Lilly means. 24 Q Did she try to put Lilly 184 1 in the best light? 2 A I would hope so. 3 Q Put Lilly's best foot 4 forward? 5 A I believe so. 6 Q And you don't have any 7 reason to believe that she was doing anything 8 other than her job with Lilly in preparing this 9 summary, do you? 10 A No. 11 Q She may have been 12 characterizing Doctor Herrmann's report even more 13 favorably for Lilly than Doctor Herrmann did 14 himself, might she have? 15 A I don't know why she 16 would. 17 Q Because she's a Lilly 18 employee and she's human and she might have been 19 interpreting in the light best to Lilly. 20 A Knowing her and having 21 worked with her for a few years, I believe that's 22 highly unlikely. 23 Q Okay. So you think that 24 her characterization, then, would be most likely 185 1 accurate? 2 A That's correct. 3 Q All right. Have you ever 4 seen any data that indicates that suicide attempts 5 have been observed more frequently on fluoxetine 6 as compared to imipramine? 7 A I am aware of this 8 question being raised. I personally did not see 9 the data, but I am aware that this issue was 10 raised by outside experts in Germany. 11 Q When were you first aware 12 of this? 13 A Again, around early 1995 14 (sic), around the same time as these meetings that 15 we discussed earlier. 16 Q With the lawyers? You 17 said early 1995. 18 A I'm sorry, 1985. 1995 is 19 next year. 20 Q That's right, neither one 21 of us were right, were we? That's not the first 22 time it's happened to me, I don't know about you. 23 What data was reviewed in 24 these discussions in early '85, the imipramine, 186 1 fluoxetine, placebo data? 2 A I'm not specifically 3 aware of the information. As I mentioned, I'm 4 aware of the issue having been raised, raised in 5 Germany only, and that there were discussions 6 ongoing internally at Lilly and with outside 7 experts as documented in the previous memorandum 8 to further define this issue. 9 Q Okay. Was it ever 10 defined? 11 A I believe it was 12 adequately defined. 13 Q The consultant there 14 opined, according to Doctor Schenk, opined the 15 probability of success that, quote, "The today's 16 knowledge of data does not justify the judgment 17 that there is a high probability of getting 18 fluoxetine registered in Germany," correct? 19 A Correct. 20 Q And the reason for that 21 was the benefit/risk ratio as discussed above, 22 correct? 23 A That's one of three 24 reasons given. 187 1 Q And the benefit/risk 2 ratio said that it was not unequivocally positive, 3 correct? 4 A That's correct. 5 Q There, apparently, Doctor 6 Herrmann, as summarized by Doctor Schenk, gave the 7 opinion that in order to have a prerequisite for a 8 successful outcome, that there might be required a 9 precautionary statement concerning suicidal risk, 10 correct? 11 A That that might be 12 necessary, yes. 13 Q And indeed that was 14 necessary, wasn't it, when it was finally 15 approved -- 16 A I believe so. 17 Q -- in 1989, is that 18 correct? 19 A Can you be more specific 20 about when you say suicidal risk? 21 Q Well, there is a -- in 22 order to be approved in Germany, what would have 23 to be marketed with package inserts or prescribing 24 information with precautionary statements 188 1 concerning suicidal risk. 2 A My interpretation is that 3 the statements in Germany were not significant -- 4 regarding suicide, were not significantly 5 different than statements in other package inserts 6 around the world which pointed out the significant 7 suicidal risk in depressed people. 8 Q When is the last time you 9 saw what was required by the German government or 10 what is currently being submitted to individuals 11 in Germany or to physicians in Germany? 12 A Probably six or seven 13 years ago. 14 Q When was Fluctin approved 15 for marketing in Germany, according to your 16 recollection, finally? 17 A Probably, it must have 18 been -- I really don't know specifically, but it 19 was probably '88 or '89. 20 Q It was '89, December 21 of '89. I'll show you some documents after we 22 take a break, to prove my veracity on that subject 23 at least. 24 A I'll accept it. 189 1 (SHORT BREAK TAKEN.) 2 (WEINSTEIN EXHIBIT NO. 9 MARKED FOR 3 IDENTIFICATION.) 4 Q (BY MR. SMITH) I'm just 5 going to ask you about the last little paragraph, 6 it's hard to read, isn't it? 7 A Okay. 8 Q Exhibit 9 is out of 9 chronological order a little bit because Exhibit 8 10 was dated in April of '85, and we're now moving to 11 January of '86, correct? 12 A Correct. 13 Q This apparently is some 14 telex from Doctor Schulze-Solce, correct? 15 A Correct. 16 Q Who is Doctor 17 Schulze-Solce? 18 A At that time, I believe 19 he was Associate Medical Director in Germany. 20 Q You are an addressee or 21 you received a copy of this document? 22 A Correct. 23 Q Do you recall receiving 24 this document? 190 1 A No. 2 Q The last -- well, I guess 3 it's the last two paragraphs, it says, quote, 4 "Concerning experts opinions in general, we may 5 mention that we already have in house: Fluoxetine 6 in general according to a list of concerns by BGA; 7 two expert opinions," then there's something 8 marked out, then it says "two expert opinions on 9 suicides and suicide attempts, phospholipidosis of 10 the lung, phospholipidosis of the eye. All of 11 these are available in English translation and 12 have been sent to Indianapolis (J. Wernicke, CC: 13 Brockwell, Gennery, Lucas, Weinstein, Zerbe) on 14 August 22, 1985," correct? 15 A Correct. 16 Q Do you recall now 17 receiving some English translations of expert 18 opinions on suicides following issues raised by 19 the BGA? 20 A My recollection is 21 limited to what this says, and I don't deny what 22 it says, I don't specifically recall those expert 23 opinions, but I -- 24 Q Do you agree that it is a 191 1 reasonable interpretation that there were expert 2 opinions on suicides and suicide attempts in 3 connection with the list of concerns by the BGA 4 that are available in English translations? 5 A Assuming that the blacked 6 out part of this communication is not relevant, I 7 would agree. I don't know what the blacked out 8 part -- whether that's supposed to modify the 9 statement or why it's blacked out. 10 MR. SMITH: Do you think 11 it's possible, Counsel, that we could get this 12 unredacted for the witness's review, at least 13 maybe to give the witness the opportunity to 14 review the document unredacted, to be of some 15 assistance to him in determining whether or not 16 it's relevant to the issue here? 17 MR. MYERS: I'll look 18 into that. Anything is possible. 19 MR. SMITH: Because, 20 obviously, we feel that this is a significant 21 issue, if there are expert opinions that were sent 22 to Indianapolis and were available at one time in 23 Indianapolis. And the representation has been 24 made that the twenty-one page Herrmann document 192 1 does not exist under the current collection of 2 Prozac documents, correct? 3 MR. FREEMAN: As far as I 4 know, that's right. 5 MR. SMITH: So that's one 6 additional reason that we would request that an 7 unredacted copy of Exhibit 9 be provided to the 8 witness, and again we're not requesting that we 9 see it, we're requesting that it be shown to the 10 witness so he can tell us tomorrow whether it has 11 any relation or modification to what it said here. 12 MR. MYERS: I understand. 13 Q (BY MR. SMITH) Do you 14 think that you would have reviewed these English 15 translations of experts' opinions on suicide and 16 suicide attempts had you been copied with such a 17 document? 18 A I think I would have read 19 them, yes. 20 Q Do you think it would be 21 maintained by somebody at Lilly, if such 22 translations had been sent? 23 A I would assume so. Only, 24 I might just point out for the sake of clarity, 193 1 that although it said they were sent to 2 Indianapolis, in fact three of the addressees are 3 not in Indianapolis. 4 Q All right. Why don't you 5 identify which three of those addressees are not 6 in Indianapolis and what their location is? 7 A Brockwell, Gennery, and 8 Lucas were located in the UK. Gennery no longer 9 works for the company; Brockwell and Lucas still 10 do. 11 Q Erl Wood? 12 A I believe, at that time, 13 all three would have been at Erl Wood, yes. 14 Q These translations, these 15 experts' opinions concerning issues raised by a 16 governmental body would not be destroyed, would 17 they? 18 A Not that I'm aware of, 19 no. 20 Q Lilly has a document 21 retention policy, do they not? 22 A Yes. 23 Q And that is to retain all 24 documents that were used in the registration 194 1 process? 2 A Yes. 3 Q And to retain documents 4 concerning expert opinions with respect to issues 5 presented by the registration process? 6 A I'm not familiar with the 7 specific policy that speaks to that issue; that 8 sounds like good practice. 9 Q What is the general 10 policy of Lilly in connection with preservation of 11 documents? 12 A I have to tell you, I 13 don't know. 14 Q All right. 15 A I retain documents until 16 whatever the prescribed time is to not retain them 17 any longer, but I have not been personally 18 involved and I don't know the specific details. I 19 know there is a written document retention policy. 20 Q Who would have that 21 document that reflected the written document 22 retention policy? 23 A I don't know who would 24 have it, perhaps the Legal Department of Lilly. 195 1 (WEINSTEIN EXHIBIT NO. 10 MARKED FOR 2 IDENTIFICATION.) 3 Q Exhibit 10 is entitled, 4 "BGA 'Unofficial' Comments on Fluoxetine", 5 correct? 6 A Correct. 7 Q There is not a date on 8 the document. Can you help us at all concerning 9 when this document would have been generated? 10 A I have no idea. 11 Q Have you ever seen this 12 document? 13 A I don't recall ever 14 having seen this document. 15 Q Do you know how Lilly 16 would come into possession or learn of a 17 regulatory body's unofficial positions with 18 respect to a drug under investigation by the 19 regulatory body? 20 A No. Again, I've never 21 seen this document and I'm not sure what it is 22 supposed to represent. 23 Q Well, if you look at the 24 stamp across it, it's a Lilly document that was 196 1 produced to us by Lilly in connection with this 2 litigation. 3 A You mean this stamp that 4 says Pz? 5 MR. FREEMAN: That's our 6 stamp. 7 A I accept that. I just -- 8 I have never seen this document and I don't know 9 what it means. 10 Q Do you know what hegemony 11 means? 12 A Yes, I always thought of 13 that in geopolitical terms, and it usually was 14 used by the former Soviet Union and other 15 Communist block countries, so I'm having great 16 difficulty understanding. 17 Q I don't know what it 18 means. What's your understanding of what it 19 means, even in the geopolitical context? 20 A I thought it had to do 21 with national interests and interfering with other 22 countries' interests and a variety -- I suppose 23 this is due to my liberal arts background, that 24 that is implied somehow in the use of competing 197 1 criteria for depression. So, if someone is saying 2 the DSM-3 belongs to -- doesn't belong to, is 3 favored by certain countries and WHO by other 4 countries, and I guess hegemony is that one of 5 these has become the dominant scale in some 6 country. I mean, frankly, I find this fascinating 7 and more for an English student than a 8 pharmaceutical company. 9 Q Do you know of any 10 English students currently employed by or formerly 11 employed by Lilly? 12 A I'm sure there must be 13 thousands, literally thousands. 14 Q Then there's another 15 heading, "Confusion," correct? 16 A Correct. 17 Q The last thing that is 18 said under that is fifteen to twenty percent ADE's 19 are CNS symptoms that may indicate worsening of 20 depression; do you see that? 21 A Correct. 22 Q Have you ever seen data 23 that indicates that the adverse experiences in 24 connection with Prozac are fifteen to twenty 198 1 percent CNS symptoms? 2 A No, I have not seen that 3 data, and again, this sentence doesn't make great 4 sense to me. If, in fact, there was worsening of 5 depression, then, by definition, that would not be 6 an adverse drug experience, so the sentence is 7 really almost impossible for me to interpret. 8 Q Under problems, it says 9 the self-rating scales are key and they show 10 little effect. Do you see that? 11 A I see that. 12 Q Are you familiar with the 13 self-rating scales that were employed in the 14 fluoxetine clinical trials? 15 A The one I'm familiar with 16 the self-rating of patient is the PGI, or Patient 17 Global Impression. 18 Q Are you familiar or are 19 you aware that those PGI scales didn't show any 20 effect in the Prozac clinical trials? 21 A No, I'm not aware of 22 that. 23 Q Are you aware of what 24 they show one way or the other? 199 1 A I thought that they had 2 showed some improvement. 3 Q Under problems, it also 4 lists no analysis of adverse experiences by 5 severity, dose or duration, correct? 6 A Correct. 7 Q Was there an analysis 8 made of the Prozac adverse experiences by 9 severity, dose or duration that you're aware of, 10 Doctor Weinstein? 11 A I believe there was. 12 Q And what were the results 13 of that analysis? 14 A The analysis that I am 15 aware of showed that the doses of sixty or eighty 16 milligrams were associated with a greater number 17 of experiences than lower doses, and I believe 18 that some of the symptoms like nausea occurred 19 earlier and then abated as time went on. 20 Q Are you speaking of any 21 connection with severity or duration? 22 A That was duration. I'm 23 not sure what analysis by severity means, in that 24 all adverse experiences that were documented to be 200 1 serious, according to FDA criteria, were, in fact, 2 reported appropriately to the various governmental 3 agencies and were listed that way. So I'm not 4 sure what adverse experiences by severity would be 5 in terms of the analysis that's being talked about 6 here. 7 Q But the title of this 8 document is "BGA 'Unofficial' Comments on 9 Fluoxetine," correct? 10 A Correct. 11 Q Which would lead a person 12 to believe that these are observations made by the 13 BGA in connection with fluoxetine, wouldn't it? 14 A Well, it would leave me 15 very confused, frankly. It's not signed, it's not 16 addressed. 17 Q It's not dated? 18 A It's not dated, and I 19 really don't know what to make of the document. I 20 haven't seen it before and I find it surprising 21 that unofficial -- even unofficial comments from a 22 regulatory agency would be portrayed in this kind 23 of nondocument. 24 Q Again, all I can help you 201 1 with, in connection with that, Doctor, is that 2 these were documents that were Lilly documents 3 that were produced to us by Lilly, that bear a 4 Lilly stamp indicating that they were, indeed, 5 documents from the files of Eli Lilly and 6 Company. 7 A I accept that. 8 Q The final sentence there 9 says, "Sixteen suicide attempts (two succeeded) 10 but excluded high risk patients so this may mean 11 fluoxetine worsens basic illness," correct? 12 A That's what it says, 13 correct. 14 Q Were you aware that there 15 were at any time sixteen suicide attempts with two 16 successes in any analysis of any data or over any 17 period of time? 18 A I am aware that in the 19 clinical trials involving fluoxetine, placebo and 20 comparators, that there were suicide attempts in 21 those trials and that there were successful 22 suicides in those trials. I am not specifically 23 familiar with the numbers that are being mentioned 24 here. 202 1 Q Are you familiar that the 2 protocols for all outpatient studies with respect 3 to the clinical trials on Prozac did, indeed, 4 exclude persons who were serious suicidal risks? 5 MR. FREEMAN: That's not 6 true. The German study would have included 7 hospital patients in a multicenter. 8 Q My question was, were you 9 aware that the outpatient protocol -- 10 MR. FREEMAN: With that 11 qualification, yes. 12 Q -- excluded serious 13 suicidal risk? 14 A Yes. 15 Q Do you think -- and 16 again, I'm not asking you to characterize this 17 document. Could that explain what they're 18 referring to when they say but excluded high risk 19 patients so this may mean fluoxetine worsens basic 20 illness? 21 A Frankly, I don't think 22 it's interpretable that way. I think it certainly 23 says that high-risk patients were excluded. I 24 don't think that that therefore means that in some 203 1 way fluoxetine would worsen the basic illness, so 2 I think there's a certain nonsequitur there. I 3 accept the fact that in the outpatient trials, 4 patients at serious risk for suicide were 5 excluded, but I do not understand and would not 6 agree that there is, therefore, data to suggest 7 that fluoxetine would worsen the basic illness. 8 Q You just disagree with 9 the conclusion of the statement? 10 A That's correct. 11 Q But again, you don't 12 consider yourself an expert on the issue that's 13 being litigated here? 14 A No. 15 Q If you were to make some 16 investigation of who authored this document, would 17 you know where to begin? 18 A No, this one would defy 19 me only because I don't even recognize the words 20 that are used as being characteristic of any of my 21 colleagues. 22 (WEINSTEIN EXHIBIT NO. 11 MARKED FOR 23 IDENTIFICATION.) 24 Q While they're looking at 204 1 that, Doctor, was it your testimony before we took 2 a break that it was your impression that the 3 package insert or prescribing information in 4 Germany was no different from prescribing 5 information worldwide in connection with 6 identifying suicide as a risk in connection with 7 the use of Prozac? 8 A That's my recollection. 9 Q I'm handing you what has 10 been marked as Exhibit 11. Take a look at that, 11 and I won't require you to read the entire thing, 12 but read Page 2 of the translation. 13 MR. MYERS: Doctor, 14 notwithstanding Mr. Smith's statement, you can 15 read as much or as little as you think is 16 necessary to answer his question. 17 A Okay. 18 Q Exhibit 11 is a 19 translation of the German package insert, and 20 there is some confusion on Page 1 of the 21 translation, the first thing that is written there 22 or typewritten there is information concerning 23 use, correct? 24 A Correct. 205 1 Q Does that lead you to 2 believe, by reading the language there, that this 3 is something that goes to the physicians in 4 Germany or the patients in Germany? 5 A I believe it's the 6 patients. 7 Q But then it goes ahead 8 and on Page 2 mentions risk patients, does it not? 9 A Yes. 10 Q It says, "Risk of 11 suicide: Fluctin" -- which is Prozac, right? 12 A Yes. 13 Q " -- does not have a 14 general sedative effect on the central nervous 15 system. Therefore, for his/her own safety, the 16 patient must be sufficiently observed until the 17 antidepressive effect of Fluctin sets in. Taking 18 an additional sedative may be necessary. This 19 also applies in cases of extreme sleep 20 disturbances or excitability," correct? 21 A Correct. 22 Q So this is a caution 23 concerning the use of Fluctin with suicide 24 patients, correct? 206 1 A It really does not -- I 2 accept that it says risk of suicide. The words in 3 the paragraph, however, really don't talk about 4 suicide, they talk about the fact that it is not 5 sedating and that co-administration of a sedative 6 may be necessary. 7 Q Well, all of that is 8 under the heading "Risk of Suicide". 9 A I recognize that, but the 10 words in the paragraph do not mention suicide. 11 Q Well, don't you think it 12 has to do that the entire paragraph is talking 13 about suicide? Why would they put it there if it 14 didn't have to do with, quote, risk of suicide, 15 colon? 16 A I'm not -- 17 Q Because, as you see 18 underneath that, there is epilepsy, colon, right? 19 A Correct. 20 Q And it describes patients 21 with epilepsy. And then above that it talks about 22 dysfunction of the liver, correct? 23 A Correct. 24 Q So, I don't understand 207 1 how you say that the language there doesn't go 2 with the heading "Risk of Suicide" and doesn't 3 pertain to the risk of suicide. 4 A I accept your statement 5 that the heading says "Risk of Suicide". The 6 subsequent paragraph does not mention suicide, and 7 does not even require the use of sedatives, it 8 says they may be necessary, so -- 9 Q Well, it says sedatives 10 may also be necessary in cases of extreme sleep 11 disturbances and excitability, doesn't it? 12 A Correct. 13 Q All under the heading 14 "Risk of Suicide", correct? 15 A It is all listed under 16 the heading "Risk of Suicide". 17 Q This language is not 18 similar to the language contained in the United 19 States PDR, is it? 20 A No. 21 Q Do you know of similar 22 language in any country other than Germany? 23 A I'm not aware of any 24 similar language other than in Germany. 208 1 Q You do know that this is 2 language that Lilly was required to distribute 3 with Prozac in Germany before they would be 4 allowed to market Prozac in Germany, don't you? 5 A Yes. 6 Q Have you seen data that 7 supports the statement that Fluctin does not have 8 a general sedative effect on the central nervous 9 system? 10 A Yes. 11 Q Have you seen data that 12 supports the statement that there is a time that 13 elapses before the antidepressive effect of 14 Fluctin, Prozac, sets in? 15 A As with all 16 antidepressants, Prozac does not work immediately, 17 or Fluctin does not work immediately. 18 Q Have you seen data that 19 supports the statement that it may be necessary to 20 take an additional sedative with Prozac? 21 A No. 22 Q Don't you know that 23 sedatives were prescribed for patients who even 24 participated in Lilly's own clinical trials? 209 1 A That's not the question 2 you asked me, Mr. Smith; you said data requiring 3 that a sedative be given, and I have not seen such 4 data. 5 Q Well, maybe my question 6 wasn't phrased correctly. Have you seen data that 7 supports the proposition that additional sedatives 8 may be necessary for patients taking Prozac? 9 A Yes. 10 Q And that sedatives may 11 be -- data supporting the proposition that 12 sedatives may be necessary for patients 13 experiencing extreme sleep disturbances or 14 excitability? 15 A May be necessary, yes. 16 Q So there is nothing 17 unscientific, as far as you know of, in any of the 18 language under the risk of suicide in the 19 prescribing information given to patients in 20 Germany, is there? 21 A Nothing unscientific. 22 Q Go back to Exhibit 5, 23 would you, Doctor, and compare that with the 24 current prescribing information or patient 210 1 information in Exhibit 11. Exhibit 5 is what 2 Lilly sent to the BGA back in 1984 that they 3 requested be contained in the prescribing 4 information for patients in Germany, correct? 5 A Correct. 6 Q That Exhibit 5 doesn't 7 have any language concerning risk of suicide, does 8 it? 9 A No. 10 Q So Lilly didn't submit to 11 the BGA any language concerning the risk of 12 suicide for inclusion in the package literature, 13 did they? 14 A No. 15 Q But before you could get 16 it marketed in Germany, you had to add this 17 language on the risk of suicide, correct? 18 A Correct. 19 Q But Lilly -- 20 A MR. FREEMAN: That 21 describes risk patients, let's keep that clear. 22 Q Yes, risk of suicide 23 under the heading "Risk Patients". 24 A Correct. 211 1 Q Did you have anything to 2 do with the decision to market Prozac with the 3 product literature contained in Exhibit 11? 4 A Yes. 5 Q Why did they make the 6 decision to go ahead and market Prozac with that 7 language? 8 A The practice of medicine 9 is different in different countries; the analysis 10 of data is different in different countries. The 11 German analysis of our data was different than 12 what we believed and different from what our 13 government believed. We frankly felt that there 14 was some modest amount of data not to suggest risk 15 of suicide, but to make it reasonable that a 16 sedative could be used in some patients, and 17 therefore felt it was acceptable for that to be 18 added in our German package insert. 19 Q Specifically, do you know 20 of any difference in the treatment psychiatrists 21 give depressed individuals in Germany as opposed 22 to the treatment that psychiatrists give depressed 23 individuals in the United States of America? 24 A I believe that there are 212 1 different rating scales that are utilized by some 2 German psychiatrists; I believe, as demonstrated 3 by the BGA, that there is interest in inpatients 4 because there is more inpatient treatment of 5 depressed people; and I believe that the approach 6 to psychiatry in Germany is, in fact, somewhat 7 different than it is in the United States or in 8 other European countries. 9 Q Have you seen some 10 analysis of that, because you, sir, are not a 11 psychiatrist, are you? 12 A Pardon me? 13 Q You are not a 14 psychiatrist. 15 A No, I'm not a 16 psychiatrist. 17 Q Have you seen some 18 analysis of the differences in the practice of 19 psychiatry in Germany than in the United States? 20 A As I mentioned, I am 21 aware of the fact that different rating scales are 22 used; I am aware of the fact that there is an 23 emphasis on inpatient treatment, and that is 24 distinctly different. 213 1 Q All right. But an 2 individual who is depressed in Germany suffers 3 from the same physiological and psychiatric 4 illness as a patient who is depressed in the 5 United States, does he not? 6 A I assume so, yes. 7 Q Medical doctors, 8 psychiatrists, attempt to treat depression in 9 generally the same way, do they not? 10 MR. FREEMAN: He's 11 already answered the question and told you they do 12 not in Germany. 13 MR. SMITH: Then he can 14 tell me they do not. 15 MR. FREEMAN: He's given 16 you two instances in which they put them in the 17 hospital more often and have a different rating 18 scale are the two instances. 19 Q (BY MR. SMITH) Rating 20 scales don't have anything to do with the 21 treatment of depression, does it, Doctor? 22 A It would seem to me that 23 it would be very important in determining whether 24 a patient was, in fact, depressed and required 214 1 therapy. 2 Q Most psychiatrists, 3 unless they're participating in some clinical 4 trial, don't sit and administer a rating scale to 5 their patients to make the determination 6 concerning whether or not they're depressed, do 7 they? 8 A I can't answer that, 9 that's -- 10 Q You're not implying that, 11 are you? 12 A I'm implying that the use 13 of rating scales in countries carries with it a 14 different approach to the treatment of psychiatric 15 illness, and no more than that. 16 Q Well, are you saying that 17 a person might be classified as depressed in one 18 country by a competent psychiatrist, but not be 19 classified as depressed by another competent 20 psychiatrist in another country? 21 A Absolutely. 22 Q All right. Well, are 23 these diagnosing criteria for depression different 24 in different countries? 215 1 A Yes. 2 Q All right. Are you more 3 likely to be diagnosed as depressed in the United 4 States or are you more likely to be diagnosed as 5 depressed in the country of Germany? 6 A I can't answer that 7 specifically. What I can tell you is, as I have, 8 that in different countries, the diagnoses is made 9 differently, the symptoms that occur may be 10 different, and the approach may be very different. 11 Q Okay, give me an 12 example. 13 A I'll give you an 14 example. If you look at the incidence of 15 depression in the country of Japan, which is not 16 on our focus of our discussion today, you will 17 find remarkably that there are very few patients 18 who appear to be depressed in Japan. Furthermore, 19 if you'll look at other countries, particularly in 20 this case in Asia, you will find that the symptoms 21 of depression tend to be totally different than 22 the symptoms seen in western countries. Most of 23 the symptoms that are seen in people in Asia are 24 what are called somatic symptoms; that is 216 1 headache, stomachache, symptoms that in no way in 2 the west would be considered as psychiatric 3 symptoms, and yet, in fact, when those people are 4 properly diagnosed and given proper antidepressant 5 medications, they will respond as would depressed 6 people in the west. So, in fact, there is data, 7 information, to suggest that in different 8 countries the disease may present in different 9 ways, the diagnoses may be made in different ways. 10 Q Okay, do you know of any 11 difference in depressed individuals in Germany 12 than in the United States? 13 A I can only repeat what I 14 have said before, clearly the approach to 15 depression in Germany is different. In Germany -- 16 Q From what respect? 17 A In Germany it's felt 18 necessary to hospitalize many patients with 19 depression; in the United States it is not felt 20 necessary to do that. 21 Q Does that mean a German 22 is more or less depressed? 23 A I can't answer that. I 24 can tell you that the approach to depression is 217 1 different in Germany, and it is different in 2 France, than it is in the United States. 3 Q Are you familiar with -- 4 and since you've expressed these opinions, I guess 5 I'll ask you -- are you familiar with what has 6 been called vegetative signs of depression? 7 A No. 8 Q Things like weight loss, 9 insomnia, decreased libido, decreased energy, as 10 being symptoms of depression? 11 A I'm familiar that those 12 can be symptoms of depression. 13 Q As opposed to saying I 14 just don't feel as up as I normally do, these are, 15 I guess, sort of objective findings of depression 16 versus weight loss, decrease in sex drive, 17 decrease in appetite, insomnia, are normally 18 things that would be considered semi-objective, 19 would they not, Doctor? 20 A Yes. 21 Q Other psychiatrists have 22 told us these are vegetative signs of depression. 23 A I accept that. 24 Q Do you know that there 218 1 is -- is there a difference in the vegetative 2 signs of depression for depressed individuals in 3 Germany versus the United States? 4 A I don't know that there 5 is or is not a difference; I'm just not aware of 6 any distinction. 7 Q But, of course, for 8 Germany, you used clinical data established in 9 clinical trials in the United States, conducted on 10 patients who were citizens of the United States, 11 correct? 12 A Primarily. 13 Q And submitted that data 14 to the German authorities in support of your claim 15 that Prozac was a safe and efficacious medication? 16 A Correct. 17 Q So I assume from that 18 standpoint, Lilly felt that depressed individuals 19 and antidepressive treatment in the United States 20 was similar enough to submit US data to them for 21 their consideration? 22 A I assume that also, and 23 as I've mentioned earlier, we were incorrect. 24 Q The BGA said we want some 219 1 German data? 2 A We want German data, and 3 we want different analyses of data. 4 Q Did they say they wanted 5 German data because they suspected that German 6 individuals would react differently to Prozac than 7 Americans? 8 A I can't assume the 9 reasons for why the BGA made that request. 10 Q Would that make any 11 sense? 12 A That's one of many 13 possibilities. 14 Q Do you, as a medical 15 doctor, think that a person, because they're 16 German, are going to react physiologically 17 different to Prozac than a person who is born in 18 the United States of America? 19 A Without launching into a 20 scientific discussion, there is a growing field 21 called pharmacogenetics in which it is abundantly 22 clear that different people of different 23 backgrounds, in fact, handle drugs differently. 24 And so to make a short answer to your question, I 220 1 don't know, but it is not outside the realm of 2 scientific possibility that a German person, whose 3 heritage may be very different than an American 4 person, may, in fact, handle a drug differently. 5 I have no knowledge that it is or is not the case, 6 but it is certainly not outside the realm of 7 scientific possibility. 8 Q Is that a generally 9 accepted scientific theory now, that people of 10 different race are going to react in a different 11 manner on a different medicine? 12 A I didn't say that. I 13 said that there is a growing field called 14 pharmacogenetics in which it is known that people 15 of different genetic backgrounds may handle drugs 16 in different ways. That is not -- it is an 17 evolving field of medicine. It leads me only to 18 say that I don't know whether Germans might be 19 different. I do know that the German government's 20 approach to the analysis of data related to the 21 treatment of depression is distinctly different 22 from those of other governments. 23 Q Who at Eli Lilly and 24 Company is examining this growing field of 221 1 pharmacogenetics? 2 A Well, there are a variety 3 of people who are learning more and more about the 4 field as we extend our clinical trials beyond the 5 United States. 6 Q Are there any 7 pharmacogeneticists employed by Eli Lilly and 8 Company? 9 A Not specifically. 10 Q Is there a 11 pharmacogenetic department at Eli Lilly and 12 Company? 13 A No. 14 Q Is there anyone that 15 holds out themselves, whether they're specifically 16 employed as that, as a person particularly expert 17 or knowledgeable at Lilly on pharmacogenetics that 18 you know of, sir? 19 A No. 20 Q Were any of these opinion 21 leaders that were consulted with, or any of the 22 outside experts consulted with by Lilly, 23 knowledgeable in pharmacogenetics? 24 A No, not that I'm aware 222 1 of. 2 Q Did they ever express to 3 you, or to anybody at Lilly, in writing that 4 you've seen, that there would be a difference in 5 the way German people handled Prozac than those of 6 the United States of America? 7 A No. 8 (SHORT BREAK TAKEN.) 9 Q (BY MR. SMITH) You had 10 mentioned earlier that it is within the realm of 11 scientific possibility that individuals of 12 different race may react differently to a 13 different drug, is that right? 14 A Yes. 15 MR. FREEMAN: He said 16 handle a drug in a different manner was his exact 17 words. 18 Q Handle a drug in a 19 different manner. 20 A Yes. 21 Q And by handling a drug in 22 a different manner, would you expect that to be 23 manifested by side effects? 24 A Not necessarily, no. 223 1 Q But it could? 2 A It could. 3 Q What you're saying is you 4 might see side effects in one race of people, but 5 not see side effects in another race of people, is 6 that what you're saying? 7 A That's possible. 8 Q Well, is it just as 9 possible, within the realm of scientific 10 possibility, that some citizens of the United 11 States of America -- in some citizens of the 12 United States of America, Prozac may be causally 13 connected with suicide? 14 A I don't believe so. 15 Q Why, just because you 16 don't accept that theory? 17 A I don't believe there's 18 data to support that hypothesis. 19 Q What data is there to 20 support that people of a different race may handle 21 a drug differently -- 22 A I will give you one 23 example. 24 Q -- than that of another 224 1 race? 2 A I will give you one 3 example: There are various enzymes in the liver 4 that are present in people of western origin that 5 are not present in people of eastern origin, and 6 I'm talking about Asia now. Those enzymes in the 7 liver, among other things, can metabolize drugs of 8 various sorts. I'm not talking about any specific 9 drug now, and in fact it is well known that the 10 drug alcohol cannot be handled very well by people 11 of Chinese extraction because they lack sufficient 12 quantities of an enzyme called alcohol 13 dehydrogenase which metabolizes the alcohol. 14 Westerners, on the other hand, are fortunate 15 enough to have enough of that enzyme in their 16 liver, so that, among other things, their liver, 17 at least for some period of time, is able to 18 handle alcohol. 19 Q Well, give me an example 20 of how this liver enzyme affects this specific 21 manufactured drug. 22 A I'm not aware of drugs 23 that have been extensively studied in Asian versus 24 western people, except for the fact that it is a 225 1 well-documented fact that the doses of drugs used 2 in Asia tend to be somewhat lower than those used 3 in the West, and that probably is related -- doses 4 on a weight basis are less, and that probably has 5 to do with the fact that there are systems in 6 Asian people which handle drugs differently, and 7 those are being actively investigated by people in 8 the scientific community. 9 Q Is anybody at Lilly doing 10 that? 11 A Not that I'm aware of. 12 Q Is Prozac being marketed 13 in Asia? 14 A Some countries. 15 Q Japan? 16 A No. 17 Q Why? 18 MR. FREEMAN: They are 19 not depressed; he's answered that earlier. 20 A It's a decision that I am 21 not involved in. 22 Q Has this difference in 23 the ability to handle a drug in Japanese versus 24 Americans caused or played any part in the 226 1 decision not to market Prozac in Japan? 2 A No, not that I'm aware 3 of. 4 Q Were you the 5 international vice president? 6 A Correct. 7 Q Give us the benefit of 8 what your opinion is on why Prozac is not marketed 9 in Japan? It's a vast market. 10 A Not for depression. 11 Q All right. 12 A As I mentioned earlier, 13 if you would speak to Japanese physicians, or to 14 the Japanese Ministry of Health and Welfare, they 15 will tell you that depression doesn't exist in 16 Japan. 17 Q Why? Do you think people 18 of that race, of the Japanese race, are less 19 likely to become depressed? 20 A I have no ability to 21 judge that. I am simply reporting to you what 22 exists in the country, what government officials 23 will tell you, and what physicians will tell you 24 there. 227 1 Q Do you agree or disagree 2 with that? 3 A I have no basis on which 4 to agree or disagree. I'm not Japanese, I don't 5 live there, I accept the words of the experts in 6 their medical community. 7 Q What's the estimate of 8 the percentage of individuals in the United States 9 who are depressed? 10 A I don't have an idea. 11 Q I'm just trying to get 12 that to ask you what the estimate is in Japan, to 13 get some difference. 14 A The only thing I can tell 15 you is that it's very much less in Japan than it 16 is here, but I don't know the specific numbers. 17 Q Is that the reason that 18 Prozac is not being marketed in Japan, because of 19 the low percentage of depressed Japanese? 20 A I'm sure that that is one 21 of many reasons why the decision was made not to 22 market, but I frankly was not involved in the 23 decision to market or not market the drug in any 24 country. 228 1 Q Do you know of any other 2 reasons why the decision was made not to market 3 the drug in Japan? 4 A I think it was probably a 5 decision based on economics, and that is based on 6 the fact that the data that is -- for any drug in 7 Japan, the data that has been generated in the 8 rest of the world is not acceptable in Japan, and 9 so everything must be generated in Japan. That is 10 not just Lilly, that is all pharmaceutical 11 companies; it is not just antidepressants, it is 12 all therapeutic classes, and I am sure that in 13 their good business sense, the leaders of the 14 company may have decided that the very significant 15 expense of developing the drug in a country where 16 there was very little use was not a wise business 17 decision. 18 Q Would there have had to 19 have been separate and individual clinical trials 20 set up in Japan and the whole process be repeated 21 in Japan? 22 A Yes. 23 Q And they wouldn't have 24 accepted any data from any studies done outside 229 1 the United States? 2 A That's correct. 3 Q Are any Lilly products 4 marketed in the country of Japan? 5 A Yes. 6 Q But the decision with 7 respect to those other products is that there was 8 enough potential people that would benefit from 9 the drug to justify the expense? 10 A That is one of the 11 elements that went into the decision. A number of 12 those products are, in fact, developed by -- 13 excuse me, are in fact marketed by a company with 14 which we've had a long-standing joint venture. 15 There are only two or three products in Japan that 16 are marketed solely by Eli Lilly and Company, and 17 those are for conditions in which it was felt that 18 the development cost was justified by the market 19 size. 20 (WEINSTEIN EXHIBIT NO. 12 MARKED FOR 21 IDENTIFICATION.) 22 Q In an effort to put 23 Exhibit 12 in context, as I understand it from 24 what we've established, the BGA issued an intent 230 1 to reject letter in February of 1985, is that 2 correct? 3 A Correct. 4 Q And as a result of that, 5 what Lilly did was withdraw their application, 6 correct? 7 A Correct. 8 Q Therefore, Lilly didn't 9 have a formal rejection, is that right? 10 A That's correct. 11 Q And this was something -- 12 does every drug company get an intent to reject 13 letter and then have the opportunity to withdraw 14 their application in an effort to possibly correct 15 a deficiency pointed out in the intent to reject 16 letter? 17 A I believe that is the 18 practice, yes. 19 Q Is that what was intended 20 to be done in connection with Prozac in Germany? 21 A Yes. 22 Q And we know that Prozac 23 was finally approved for use in Germany in 24 December of 1989? 231 1 MR. FREEMAN: Modify the 2 question and say was approved, not finally was 3 approved. 4 Q Well, they received final 5 approval in December of 1989, right? 6 A Yes. 7 Q Finally. In July 1987, 8 two and a half years after the intent to reject 9 letter, and a year and a half before it was 10 approved, the question of suicide and activation 11 was still a concern of the BGA, is that correct? 12 A No, I can't confirm 13 that. All I can confirm is that we received the 14 concerns of the BGA in 1985, as you suggested, the 15 submission was withdrawn while we had the 16 opportunity to work to answer the questions that 17 had been raised by the BGA, and I'm not even aware 18 whether there were active communications going on 19 with the BGA in the interim, between the 20 withdrawal of the submission sometime in 1985 and 21 it's subsequent resubmission later. 22 Q Do you know when it was 23 resubmitted? 24 A I don't know specifically 232 1 when it was resubmitted; I would assume, if it was 2 approved in late 1989, that it probably was 3 resubmitted in 1987, or thereabouts. 4 Q Why, because of your 5 familiarity with the time it usually takes the BGA 6 to act? 7 A The time. 8 Q Did the process have to 9 be totally redone in connection with the 10 application after the intent to reject and after 11 the original application was withdrawn? 12 A Well, if by the process 13 you mean did we have to make the full submission 14 again, I believe the answer is yes. 15 Q All right, so all the 16 data that had been submitted earlier had to be 17 resubmitted? 18 A I believe so. 19 Q So would that have to do 20 with clinical trial information? 21 A I believe so. 22 Q Would you have submitted 23 different data or the same data plus additional 24 information? 233 1 A I believe it would have 2 been the same data plus additional information. 3 Q Would the -- and I'm not 4 asking you to look into the brain of the BGA, but 5 based on your experience, would this have required 6 a re-analysis of data that had been originally 7 submitted in the original application? 8 A I'm sorry, who would be 9 doing the re-analysis? 10 Q The BGA, or I guess it's 11 the commission. 12 A Presumably they would 13 analyze the data anew. I don't know the internal 14 workings of Commission A, but I would assume that 15 once the data had been -- or the submission had 16 been withdrawn, and then subsequently resubmitted 17 a couple of years later, that they would have 18 started afresh in their analysis of the data, the 19 old data and the new data, but as you suggested, I 20 can't look inside their brains. 21 Q Well, at least in July 22 1987, this document, which is a document directed 23 by Doctor Wernicke to Doctors Draper, Lemberger, 24 Leigh Thompson and yourself, indicates that toward 234 1 the last of the last paragraph, the questions of 2 suicide and possible activation was raised. 3 Doctor somebody seemed quite concerned about this, 4 he has a scientific interest in serotonin and 5 mechanisms of action of serotonin uptake 6 inhibitors, correct? 7 A That's what it says, yes. 8 Q And all this is preceded 9 by the fact that this doctor, who was blacked out, 10 gave Doctor Wernicke some insights into why 11 fluoxetine was not approved by the BGA, right? 12 A Yes. I hope that you 13 will also note that in the last paragraph, Doctor 14 Wernicke says that he got the impression that he 15 was comfortable with our conclusion of the lack of 16 a correlation of use of fluoxetine and suicidal 17 behavior. 18 Q This fellow that you 19 brought over to explain to you why the BGA 20 rejected Prozac was telling you about what his 21 opinion was in connection with the safety of 22 Prozac, right? 23 A No, I'm simply mentioning 24 that, as you pointed out, he had concerns about 235 1 suicide, and Doctor Wernicke's statement in the 2 last paragraph on the first page of this memo is 3 that he is comfortable with our conclusion that 4 there was a lack of correlation between 5 administration or use of fluoxetine and suicidal 6 behavior. 7 Q Yes, but the point I'm 8 making is, when it says he there, you're talking 9 about this expert that has been blacked out -- 10 A Yes, whoever this person 11 is, yes. 12 Q -- that was brought over 13 to tell you why Prozac was not approved by the BGA 14 in Germany, correct? 15 A Two years earlier, yes. 16 Q Two years earlier, and 17 who, two years after it was rejected, was still 18 telling Doctor Wernicke that the question of 19 suicides and possibility activation was still a 20 concern, correct? 21 A That is correct. 22 MR. SMITH: Let's take a 23 break. 24 (SHORT BREAK TAKEN.) 236 1 Q (BY MR. SMITH) Infor- 2 mation that was going to be required by the German 3 government that should have been known before any 4 application was made to the German government in 5 connection with the marketing of Prozac for 6 depression in Germany, shouldn't it? 7 MR. FREEMAN: He's 8 answered that already, but we'll let him answer it 9 one more time. 10 A I don't understand the 11 question. 12 Q Well, you've indicated 13 that, for instance, Germany requires more 14 in-hospital studies than does the United States. 15 My point is that wasn't something that came up 16 right at the last, was it; it was known all along 17 that Germany required more in-hospital studies? 18 A No, it was not known all 19 along. We knew it after we had made the 20 submission, and when the BGA reviewed it, they 21 pointed out that they wanted more inpatient data. 22 Q Was there more inpatient 23 data generated? 24 A I believe so. 237 1 Q Who did that? 2 A Independent investigators 3 in Germany and, I believe, Austria or Switzerland. 4 Q Did they require more 5 inpatient data for patients hospitalized in 6 Germany, or would inpatient data of the United 7 States have been sufficient? 8 A I'm not really certain. 9 I think their issue was more inpatient data than 10 the particular country in which those patients 11 happened to be hospitalized. 12 (WEINSTEIN EXHIBIT NO. 13 MARKED FOR 13 IDENTIFICATION.) 14 Q Exhibit 13 is a document 15 authored by Doctor Claude Bouchy dated August 30, 16 1989, is that correct? 17 A Mr. Bouchy, yes. I'm not 18 aware that he's a doctor. 19 Q He marks this document 20 confidential, does he not? 21 A Yes. 22 Q It's addressed to Brian 23 Gennery, correct? 24 A Correct. 238 1 Q Who is that? 2 A The former group medical 3 director for Europe based at Erl Wood. 4 Q And I think we identified 5 all the other addressees, correct? 6 A Correct. 7 Q The subject of the memo 8 is "Additional Feedback Regarding the Fluoxetine 9 Review by the Commission A", correct? 10 A Correct. 11 Q And he says, "Through 12 additional contacts I have been able to find out 13 the following information," right? 14 A Right. 15 Q Do you know what 16 additional contacts he had that enabled him to 17 know what Commission A was going to do or not 18 going to do? 19 A No. 20 Q He says, No. 1, only the 21 twenty-milligram pack will be registered, and the 22 thirty-milligram, forty-milligram and sixty- 23 milligram packs will be denied registration on the 24 ground that we have demonstrated the twenty 239 1 milligrams is the right dose, correct? 2 A Correct. 3 Q What is pack in 4 connection with these dosage forms? 5 A My assumption is that it 6 is a package that has a certain number of twenty- 7 milligram capsules in it, but I really am not 8 involved specifically in the packaging or that 9 sort of thing anywhere in the world. 10 Q In the United States, 11 Prozac is sold in bulk to distributors, as I 12 understand it, and those distributors sell it in 13 lesser bulk to pharmacies. 14 A That's correct. 15 Q Then if you and I are 16 prescribed a prescription for Prozac, we take that 17 to our pharmacist, he fills the prescription, as 18 per the doctor's instructions, and we get a bottle 19 with a number of pills, correct? 20 A That's correct. 21 Q Do you understand that 22 there was a different way of dispensing 23 medications in Germany? 24 A There's a different way 240 1 of dispensing medications in most of the countries 2 of the world. What you described for the United 3 States is rather unique to the United States. In 4 most countries, a given smaller amount of medicine 5 is distributed in the packets. That may involve 6 one week of therapy, two weeks of therapy, but the 7 kind of repackaging, if we can use that term, that 8 is done in pharmacies in the United States is not 9 done in most of the rest of the world. And so the 10 manufacturer is required to manufacture an 11 appropriate size package for the patient. 12 Q Does the patient get that 13 package at a pharmacy? 14 A Depending on the country, 15 they may get it at a pharmacy or at a hospital; it 16 would depend on what the health care system is. 17 Q So when they talk about 18 packs, they're probably talking about this 19 different mode of dispensing the prescription? 20 A Correct. 21 Q Point 3 indicates the 22 contraindication because of acute suicidality 23 should become a warning whereby the physician 24 should be advised that in the absence of sedation, 241 1 the risk of higher suicidality should be taken 2 into account, correct? 3 A Correct. 4 Q That indicates to me that 5 the BGA is indicating that there is a risk of 6 higher suicidality with Prozac in the absence of 7 sedation, correct, am I correct? 8 A That is correct. 9 Q And that's going to be a 10 warning to the physician, correct? 11 A That's correct. 12 Q As opposed to something 13 that's given to the patient in the patient 14 literature? 15 A Yes, and also as opposed 16 to a contraindication. So, in fact, it would 17 appear from this that a contraindication, which 18 would forbid the use of the drug in such patients, 19 is in fact not felt to be appropriate, and simply 20 a warning which advises the physician of this 21 possibility is what the BGA apparently is going to 22 say. 23 Q It doesn't say the word 24 possibility in any word there in that Paragraph 3, 242 1 does it? 2 A It says the risk should 3 be taken into account. 4 Q It doesn't say 5 possibility, does it? 6 A It doesn't say 7 possibility. 8 Q It says the 9 contraindication because of acute suicidality, 10 doesn't it? 11 A Correct. 12 Q Acute suicidality is 13 something that arises within a short time, is it 14 not? 15 A I am not sure what you're 16 saying. Can you -- 17 Q Then why don't you define 18 acute as it's used in medical terms, Doctor? 19 A I think -- as defined 20 here, I suspect that what this means is there is a 21 possibility not that this developed acutely, but 22 that there is a possibility that suicide might 23 occur acutely; that is, there is a short-term risk 24 that the patient -- or there is a risk in the 243 1 relatively short term that the patient might 2 commit suicide. 3 Q Or it could be as easily 4 said that there is a short-term risk of 5 suicidality, couldn't it? 6 A That's correct. But it 7 is not correct to say you, as you said, that this 8 arose recently, which was your initial 9 character -- 10 Q Acute means -- 11 A Acute means ongoing now, 12 of short duration. 13 Q Of short duration, that's 14 why I used the term shortly. 15 A But -- okay. 16 Q And I wasn't incorrect in 17 using the term shortly in that aspect, was I? 18 A No, you're not incorrect 19 in using that. I believe my interpretation, 20 though, is somewhat different. 21 Q Well, it says what it 22 says, doesn't it? 23 A And we do not agree on 24 our interpretation. 244 1 Q All right. It also 2 speaks of a risk of higher suicidality as well as 3 acute suicidality, doesn't it? 4 A It only speaks of a risk 5 of higher suicidality, it doesn't speak of a risk 6 of acute suicidality. 7 Q Well, it says, "The 8 contraindication because of acute suicidality 9 should become a warning," doesn't it? 10 A Yes, and I hope you 11 recognize that that means that in fact this 12 interpretation is less worrisome than it had been 13 initially since contraindication means the drug 14 absolutely must not be used, and warning is the 15 possibility should be taken into account by the 16 prescribing physician. 17 Q I understand that, 18 because I would assume that -- well, I assume that 19 this is something that Lilly was lobbying for a 20 warning to occur; that is, instead of a 21 contraindication, where there would be a 22 prohibition, there would be a warning of this 23 risk, correct? 24 A Lilly would certainly be 245 1 happier with that than the contraindication. 2 Q Lilly was happier with a 3 warning in that instance than with a prohibition? 4 A Than with a 5 contraindication, yes. 6 Q It also says the 7 contraindication for agitated patients and for 8 patients with pronounced sleep disturbances should 9 not be made -- should not be an absolute 10 contraindication, but rather a relative 11 contraindication. This in Germany is very similar 12 to a precaution whereby physicians would be 13 particularly careful with these patients, correct? 14 A Correct. 15 Q So I guess 16 contraindication is a term that says don't 17 prescribe it, right? 18 A Correct. 19 Q Warning is a term that 20 indicates take this risk into account when you 21 prescribe it, right? 22 A Correct. 23 Q And a relative 24 contraindication would be a situation where a 246 1 physician should be particularly careful with a 2 particular group of patients, is that right? 3 A Yes, it would be less 4 stringent than a warning. I might point out that 5 this is being -- I think what Mr. Bouchy is doing, 6 although it's difficult for me to get inside his 7 head, is that he is referring to terms that 8 normally appear in US package inserts, and the 9 phrases precaution, warning and contraindication, 10 are normal parts of US package literature for all 11 products, and I think he is trying to draw 12 analogies here between what appears in the United 13 States FDA approved literature and what is being 14 proposed for Germany. 15 Q So what he's saying is, 16 whether you use the term contraindication or 17 warning, he's saying that a physician should be 18 particularly careful in agitated or sleep 19 disturbed patients, right? 20 A He's saying that that's 21 what his apparent contacts have informed him, yes. 22 Q And that in connection 23 with patients who might be suicidal, that a 24 physician should be warned of a higher risk of 247 1 suicidality in the absence of sedation? 2 A That's what it says. 3 Q And this is, in fact, 4 what occurred, is it not? 5 A Yes. 6 (WEINSTEIN EXHIBIT NO. 14 MARKED FOR 7 IDENTIFICATION.) 8 Q Exhibit 14 is a series of 9 three -- what are they, telexes? 10 A They're electronic mail. 11 Q E-mails, over a period 12 from December 6, 1989 until December 7, 1989, 13 correct? 14 A Correct. 15 Q All are authored by 16 Claude Bouchy? 17 A Correct. 18 Q And all have to do with 19 registration of Prozac in Germany, right? 20 A Right. 21 Q And on the first page, 22 Bouchy does indeed say fluoxetine registered in 23 Germany at last, doesn't he? 24 A Actually there's a 248 1 question mark afterwards, so I'm not sure whether 2 this means that it was registered or not. 3 MR. FREEMAN: It does not 4 use the word finally. 5 Q The sense of the three 6 pages is, in fact, that you're going to get Prozac 7 registered in Germany, but that there's going to 8 be some prescribing information and package 9 literature that are not entirely acceptable, 10 correct? 11 A Correct. 12 Q And that there is going 13 to be, in fact, an appeal of some of the language, 14 or they're contemplating appealing some of the 15 language, correct? 16 A Correct. 17 Q And in fact, Page 3 18 indicates that an appeal could be raised after 19 registration was approved, and you could contest 20 the language later, but continue to market Prozac, 21 is that right? 22 A Correct. 23 Q And that's what was 24 suggested by your lawyer there in Germany, right? 249 1 A Yes. 2 Q Straeter, your lawyer, 3 who was consulted in the registration of Prozac in 4 Germany, had in fact been the lawyer for the BGA, 5 hadn't he? 6 A Previously, yes. 7 Q I'm not implying at the 8 same time, but previously had represented the BGA 9 or had been the lawyer for the BGA? 10 A I believe he had been a 11 lawyer for the BGA, yes. 12 Q But in this instance, he 13 was representing Eli Lilly and Company, or its 14 German affiliate, in assisting in registering 15 Prozac? 16 A I'm not sure I would 17 characterize it that way. He was certainly giving 18 us information about the registration process. I 19 don't know that he personally was involved in 20 registering Prozac. I think he knew the policies 21 and methods of the BGA and was providing us 22 information on what would be appropriate to 23 submit. 24 Q Well, on the first page, 250 1 that last paragraph, it says, on the other hand -- 2 the last paragraph of the first page of Exhibit 14 3 in fact says, quote, "On the other hand, if we 4 decide to accept it, we can type the registration 5 document in house on our old Siemans word 6 processor, Straeter can take the disquettes (sic) 7 to Berlin, and we can have the registration for 8 Christmas or New Years with a launch end of 9 February or early March," correct? 10 A Correct. 11 Q So Straeter is taking the 12 diskette to Berlin for you? 13 A With all due respect, 14 Mr. Smith, I think Straeter was being used as a 15 delivery person since he lives in Berlin and our 16 office is hundreds of miles away. I don't think 17 that this is part of the registration process. I 18 think he was probably being a nice man and 19 bringing the diskettes to the BGA, period. 20 Q Well, look at Page 2, 21 then, the last paragraph of Page 2, "I wish to 22 reassure every one on this. First of all, 23 generally, all our dealings with the BGA are made 24 under advice of a lawyer and not any lawyer but 251 1 the former legal head of the BGA (Straeter)," 2 correct? 3 A Correct. 4 Q So he's giving Lilly 5 advice as a lawyer, isn't he? 6 A Yes. 7 Q I took it by that, that 8 he had been employed by Lilly or your German 9 affiliate? 10 A All I'm saying is that he 11 did provide advice, he was not actively involved 12 in the registration process. He provided advice 13 so that we could understand how the BGA works and 14 helped us to interpret some of the information 15 which had been sent from the BGA simply because he 16 was a former employee. 17 Q So is it your testimony 18 he wasn't acting as your lawyer? 19 A I don't know that he was 20 acting as our lawyer; I'm not sure that we had any 21 particular legal dealings with the BGA. We made a 22 submission, we received a letter of intent to 23 reject, we withdrew the submission, we did what we 24 felt was appropriate to try to get the drug 252 1 approved in Germany, and I know he provided advice 2 to us because he understood the working of that 3 agency and their requirements better than we did 4 as a former employee. I'm not aware that he 5 represented us as an attorney in front of that 6 agency, no. 7 Q All right. Page 3 is 8 entitled "RE: The Fall of the Other Berlin Wall", 9 correct? 10 A Correct. 11 Q Obviously, the actual 12 fall of the Berlin Wall was an event of extreme 13 historical importance? 14 A Correct. 15 Q Do you have any judgment 16 concerning why Claude Bouchy would have referred 17 to the registration of Prozac in Germany in terms 18 as he did? 19 A My only understanding is 20 that you have to understand Mr. Bouchy is French. 21 Q All right. 22 A French people get very 23 emotional about a number of things, and I assume 24 that as a Parisian, he saw this as a great event, 253 1 particularly in view of the fact that he was the 2 general manager of Lilly and responsible for his 3 business of the company in Germany. But I cannot 4 crawl into Mr. Bouchy's head to explain why he 5 would use the words he did. 6 Q Could it be interpreted 7 that he saw this as a significant obstacle that 8 had been overcome by Lilly? 9 A That certainly is one 10 reasonable interpretation. 11 Q When did Claude Bouchy 12 leave Lilly? 13 A I'm not familiar, it 14 was '91 or '92, I believe, but that could be 15 incorrect. It was certainly after those events. 16 Q Do you have any idea 17 where he is now? 18 A No. 19 Q You say he's a Frenchman 20 and you mentioned Parisian. Do you think he's 21 back in Paris, France? 22 A I don't know where he is 23 now. I would have assumed that he would have left 24 Germany because that was a place that he was 254 1 assigned to by Lilly, but I've not had any contact 2 with him since he left. 3 (WEINSTEIN EXHIBIT NO. 15 MARKED FOR 4 IDENTIFICATION.) 5 Q I think Exhibits 5 and 10 6 that we discussed earlier are drafts and final 7 translations of information that goes to the 8 patient via a package insert of sorts, is that 9 correct? 10 A Correct. 11 Q And what's being 12 transmitted to you in Exhibit 15 dated December 6, 13 1989 is the information for professionals, which 14 would be the information that is given to 15 physicians prescribing the medication, is that 16 right? 17 A Correct. 18 Q And would this be similar 19 to information contained in the PDR in the United 20 States? I mean as far as it being for 21 professionals as opposed to it being the exact 22 same wording. 23 A The exact same words -- 24 oh, yes, it would be for professionals, like the 255 1 PDR, or as you know, the PDR can be bought at any 2 bookstore, so it's beyond professionals now. 3 Q Is there any information 4 that accompanies Prozac in the United States for 5 patients to use or read about in learning about 6 the properties of Prozac, as far as you know? 7 A No, I'm not aware of any 8 specific information for patients. 9 Q We talked about specific 10 information for patients in Germany, correct? 11 A Correct. 12 Q Is there information for 13 patients that's distributed in any other 14 countries, in addition to Germany? 15 A As I mentioned, there 16 were, at this time, a few other countries that 17 required patient information, and I believe two of 18 those countries are Belgium and Spain, and that in 19 fact some form of patient information was provided 20 according to the laws of those countries. 21 Q How about the United 22 Kingdom and France? 23 A I do not believe that at 24 the time there was patient information required in 256 1 the United Kingdom, and I frankly just don't know 2 about France. 3 Q When was Prozac approved 4 in Belgium? 5 A I believe it was 1986. 6 Q How about in Spain? 7 A It was probably 1987 or 8 1988, but I don't know or recall specifically. 9 Q Back to Exhibit 15, the 10 information for professionals that was 11 incorporated, was used in Germany, finally, had 12 sections for precautions in patients at risk, did 13 it not? 14 A Yes. 15 Q On page, I guess, four? 16 A Four. 17 Q Yes, F4. It says 18 precautions in patients at risk, does it not? 19 A Yes. 20 Q Under that it talks about 21 liver and kidney metabolism, then under that it 22 says, continuing under precautions in patients at 23 risk, it says fluoxetine does not generally act 24 sedating, does it? 257 1 A Correct. 2 Q It says, "Until the onset 3 of depression alleviating effects, the patients 4 have to be observed adequately. In patients with 5 suicidal risk, continuous observation and/or 6 generally sedating additional therapy may be 7 necessary. In patients suffering from agitation 8 or marked sleep disturbances, Fluctin has to be 9 used with special care," correct? 10 A Correct. 11 Q And that's again 12 reflective of those different warnings and 13 precautions and contraindications being termed to 14 relative contraindications as was discussed in the 15 Bouchy document that we've earlier marked as your 16 Exhibit 13, correct? 17 A Yes, it seems very 18 similar. 19 Q Additionally, there is 20 data in that information for professionals 21 concerning treatment of emergent adverse event 22 experience, doesn't it? 23 A Yes. 24 Q And that's listed on Page 258 1 F6? 2 A Yes. 3 Q There that compares 4 various adverse events that were experienced on 5 patients on Prozac as compared to placebo or no 6 drug, right? 7 A Correct. 8 Q And there it lists 9 nervous as an adverse event that occurred in a 10 greater percentage than on placebo, does it not? 11 A A greater percentage, 12 yes. 13 Q It lists nervousness also 14 as an adverse event that occurred in a greater 15 percentage of Prozac patients than placebo 16 patients? 17 A Let me just return to the 18 previous question. In fact, there's nothing that 19 I can find listed under nervous, I'm not sure why 20 that statement or why that word is in there, 21 because there are no numbers in my copy that 22 correspond to the word nervous. 23 MR. FREEMAN: It starts 24 with headache, I believe. 259 1 A It starts with headache. 2 Q I was going to ask you 3 why they had nervous and nervousness again. 4 A I think that must be a 5 misprint or typographical error or something. 6 Q I bet it's because -- if 7 you look in the upper left-hand corner, it says 8 body system, adverse event, and they're talking 9 about the nervous system. 10 A That's just a header, 11 right. 12 Q So they showed 13 nervousness under the nervous system -- 14 A Correct. 15 Q -- as an event that was 16 reported in a greater frequency than on placebo? 17 A The numbers are higher 18 with the fluoxetine group than with the placebo 19 group. Unfortunately, there's no statistical 20 analysis that accompanies this to show us whether 21 these differences are significant. 22 Q Wait a minute. Is it 23 your testimony, Doctor, that you don't know 24 whether or not this listing of adverse events in 260 1 the German package insert has been analyzed for 2 any statistical significance? 3 A No, I didn't say that. I 4 said the statistical analysis is not printed here, 5 and so I can answer your question affirmatively by 6 saying the numbers are higher in the fluoxetine 7 group. 8 Q This is percentages, this 9 is not numbers, isn't it? 10 A Yes. 11 Q So I take it, under 12 nervousness, fourteen percent of the individuals 13 on Prozac reported nervousness, where eight point 14 five percent of the individuals on placebo 15 reported nervousness; am I incorrect? 16 A You're correct. 17 Q Okay. So what does 18 the -- you're saying you want a statistical 19 analysis? 20 A No, no, I didn't say I 21 wanted a statistical analysis. I simply pointed 22 out that there is not one here to tell me whether 23 these are statistically significantly different 24 incidences. 261 1 Q That's just a scientific 2 judgment that statisticians use as to whether or 3 not a difference is a statistically significant 4 difference, correct? 5 A It is statistics, and I 6 am certainly not an expert, and statistics are 7 based on certain principals that are generally 8 accepted for what differences are, in fact, 9 statistically significant, and in most cases, 10 those involve a difference that would be five 11 percent or less likely to happen simply by chance. 12 Q All right. 13 A I assume that these have 14 been subjected to a statistical analysis. I 15 simply mentioned that it is not available to me 16 here, so all I can tell you is, yes, the numbers 17 are higher in the fluoxetine group. 18 Q Doctor Weinstein, this is 19 Lilly's data and reviewed by Lilly statisticians. 20 A I'm aware of that. 21 Q All right. Is it 22 accurate -- whether there's a statistical 23 significance to any of this, is it accurate what 24 they're reporting in the German package insert, 262 1 that fourteen point nine percent of the patients 2 on Prozac were reporting nervousness, while eight 3 point five percent of the patients on placebo were 4 reporting nervousness? 5 A In these placebo 6 controlled clinical trials, yes. 7 Q Lilly placebo controlled 8 clinical trials? 9 A Yes. 10 Q Insomnia, thirteen point 11 eight percent of individuals on Prozac reported 12 insomnia, where seven point one percent on placebo 13 reported insomnia? 14 A Correct. 15 Q That looks to me like 16 almost twice as many people reported insomnia on 17 Prozac than on placebo. 18 A Thirteen point eight is 19 almost twice seven point one, yes. 20 Q And I'm not a 21 statistician, but I would say that there probably 22 would be a statistical significance to that, 23 wouldn't you, as an individual with a high degree 24 of intelligence and training? 263 1 A There probably was a 2 statistical significance. 3 Q Anxiety was reported in 4 nine point four percent of the patients on Prozac, 5 and reported by five point five percent of the 6 patients on placebo, correct? 7 A Correct. 8 Q It looks like there was a 9 three to two difference in that particular 10 difference. 11 A Correct. 12 Q Beg your pardon? 13 A Correct. 14 Q I would think that would 15 be statistically significant, a three to two 16 difference, wouldn't you? 17 A It might well be, and it 18 might well not be, I really don't know. I haven't 19 subjected these to statistical analysis, I assume 20 others have done that. 21 Q Do you know how to do 22 that? 23 A Yes. 24 Q What would you do? 264 1 A I would look -- the first 2 thing I would look at is the sample size, and then 3 using various formulas, which I would have to look 4 up because I'm not well enough versed in this to 5 keep them in my head, I would plug it into my 6 little hand calculator and figure out what the P 7 value was. 8 Q What's your understanding 9 of what P value is? 10 A It is the likelihood that 11 these instances or these differences in any kind 12 of analysis have occurred by chance, or because 13 there are real differences between the groups 14 being compared. The usual level that is used is 15 five percent; that is, if one can demonstrate that 16 there is a ninety-five percent likelihood that 17 there are real differences or greater, then that 18 is a statistically significant difference. But if 19 there was a ninety percent likelihood, by usual 20 scientific criteria, people are not willing to 21 accept that as showing a scientifically valid 22 statistical difference. 23 Q Could it be said another 24 way, that if the difference was greater than five 265 1 percent, that it would be statistically 2 significant? 3 A If the difference was 4 greater than -- 5 Q If you're saying -- 6 A Yes, yes -- no, no, I 7 don't understand the question. Say it again. 8 Q All right. You said 9 earlier that five percent is a value that could 10 occur by chance, is that right? 11 A If it's greater than five 12 percent, if there is -- if the chance that the 13 difference between these two groups is -- let me 14 figure out a better way to express this. 15 If it is ninety-five 16 percent or more likely that the difference between 17 these two groups is real and not simply related to 18 chance, then that is regarded as scientifically 19 significant, in most sciences. If it is felt that 20 there is a less than ninety-five percent chance 21 that there is a real difference, that is a five 22 percent or greater chance that this just happened 23 without a real difference between the two groups, 24 then that has not generally been regarded as 266 1 scientifically valid, and this goes beyond 2 medicine into a variety of other scientific 3 fields. 4 Q Well, I won't embarrass 5 you by debating statistics with you. 6 MR. FREEMAN: We're 7 delighted over that. 8 Q Turn with me, finally, to 9 the last questions of the day, to Page 10. It 10 says, "When fluoxetine and other antidepressants 11 are taken at the same time, previously stable 12 plasma levels of these antidepressants can be 13 elevated up to more than double. Therefore a dose 14 adjustment or dose reduction, resp., of the 15 antidepressant is necessary." 16 A Respectively. 17 Q Then the next page says, 18 "As elimination of diazepam is delayed by 19 fluoxetine, it's effect can be increased," 20 correct? 21 A Correct. 22 Q Diazepam is a 23 tranquilizer, correct? 24 A Correct. 267 1 Q Is diazepam a 2 benzodiazepine? 3 A Yes. 4 Q And is that saying that 5 if you give Prozac and diazepam, or a 6 benzodiazepine, that you're likely going to have 7 more effect of the diazepam, it's going to act 8 longer? 9 A I would not say likely; 10 it is possible that there could be a prolonged 11 effect. 12 Q In other words, five 13 milligrams of Valium might make you sleepier than 14 if you weren't taking Prozac? If you were taking 15 Prozac and you were given five milligrams of 16 Valium, there is the possibility that the potency 17 of that five-milligram dose of Valium would be 18 increased? 19 A I don't think that that 20 is what it's saying. My interpretation of this is 21 that the elimination is delayed, which would mean 22 that the effect might be longer lasting rather 23 than the potency increased, based on this 24 statement that you've read. 268 1 Q It says it's effect can 2 be increased. 3 A Effect, that's right, but 4 my impression is, based on this statement, it says 5 the elimination of diazepam is delayed by 6 fluoxetine, I'm assuming, based on this limited 7 amount of information, that if elimination is 8 delayed, it will not increase the effect, but it 9 may well prolong the effect. 10 Q All right, so if I took 11 five milligrams of diazepam, a tranquilizer, I 12 might be less agitated longer? 13 MR. FREEMAN: You might 14 take your next dose later. 15 A You might take your next 16 dose late. 17 Q Because -- 18 A Because the drug, in some 19 small number of patients, may be eliminated 20 slower. 21 Q Where does it say in a 22 small number of patients it would be eliminated 23 slower? 24 A My recollection of the 269 1 data, and this is admittedly somewhat limited, is 2 that this was not a consistent finding in all 3 patients. That is my recollection of the 4 information that led to this change, and that the 5 change -- that the elimination changes were 6 relatively minor. 7 Q When you say you'll take 8 your next dose later, are you talking about the 9 Prozac or the diazepam? 10 A Diazepam. 11 Q The tranquilizer? 12 A The tranquilizer. 13 (OFF-THE-RECORD DISCUSSION HELD.) 14 (DEPOSITION 15 ADJOURNED FOR THE DAY.) 16 17 * * * * * 18 JUNE 30, 1994 19 * * * * * 20 Q (BY MR. SMITH) Doctor, 21 would you look with me again on Exhibit 6 for a 22 minute? And for your recollection, this is a 23 telex from Doctor Weber and others in connection 24 with the unofficial communication from the BGA 270 1 that the registration would not be accepted as a 2 result of efficacy questions and suicidal risk, 3 correct? 4 A Correct. 5 Q In that document, Doctor 6 Weber suggests, in the meantime, the following 7 action plans have been initiated on fluoxetine, 8 and there was going to be a meeting of February 4 9 with Lilly's clinical expert to discuss the 10 possible ramifications of the BGA position, 11 correct? 12 A Correct. 13 Q Do you know who it would 14 have been that Lilly had at the time in Germany 15 who was a clinical expert in connection with 16 Prozac? 17 A No. 18 Q Was there a group of 19 individuals in each country that, in your 20 experience, Lilly dealt with in connection with 21 the various products? 22 A I'm not aware of any 23 formal group, no. 24 Q Would this have been a 271 1 clinical trial investigator or would this have 2 been someone of an independent sort? 3 A I can't comment. I don't 4 know who they would have selected as a clinical 5 expert. It could have been either one of those, 6 or neither. 7 Q Clinical expert, as I 8 understand it, would be probably a physician who 9 treats patients? 10 A That's correct. 11 Q As opposed to maybe a 12 professor that was hired to address a particular 13 issue or someone like Straeter who helped in 14 regulatory bodies, correct? 15 A No, a clinical expert 16 could be a professor who had experience in 17 clinical medicine, or it could be a practicing 18 physician whose primary role is to take care of 19 patients. My interpretation of clinical expert 20 means someone expert in clinical medicine, and 21 that does not necessarily apply to either one of 22 those options that you suggested. 23 Q All right. One doesn't 24 necessarily exclude the other? 272 1 A No. 2 Q Under that it lists, as 3 far as an action plan, immediate follow-up on all 4 key opinion leaders on the BGA commission for 5 selected visitation next week. I interpret that 6 to mean that there were key opinion leaders on the 7 BGA that were going to be contacted, is that 8 right? 9 A No, they're not on the 10 BGA. The commission is an outside organization 11 that is the advisory group to the BGA, that is 12 distinctly different from the BGA, which is the 13 government regulatory agency. 14 Q All right. But the plan 15 was to talk with these key opinion leaders on the 16 commission that were making the recommendation to 17 the BGA concerning whether or not to approve the 18 product, is that right? 19 A That appears to be right. 20 Q And Lilly was going to 21 specifically follow up with the key opinion 22 leaders on the commission? 23 A That's what the telex 24 says. 273 1 Q And have selected 2 visitation with them the following week? 3 A Yes, that's what it says. 4 Q Do you know if that was 5 done? 6 A No. 7 Q Do you have an opinion 8 concerning whether that would be appropriate or 9 inappropriate, to go directly to members of the 10 commission to talk with them directly concerning a 11 matter that they're supposedly impartial on? 12 A The members of these 13 commissions in Germany are identified publicly, 14 and it would not be unusual for any company to 15 interact with them. 16 Q And try to influence 17 their opinions with respect to the safety and 18 efficacy of a product? 19 A I don't read this as 20 suggesting that there was influence that was being 21 utilized; it simply says follow-up with these 22 individuals, and I can interpret this also as 23 following up to try to obtain more information. 24 Q From the members of the 274 1 commission? 2 A Certainly. If, in fact, 3 we had unofficially received information that the 4 commission had made certain judgments, it would 5 seem very logical, if we knew the members who had 6 been publicly identified and who are well-known 7 throughout Germany, to meet with those people to 8 ask them what the issues were that they discovered 9 in their review of the dossier. 10 Q That might be one 11 explanation, but it could also be that you were 12 seeking to influence their opinion. When I say 13 you, I'm talking about Lilly. 14 A I think it's highly 15 unlikely that any pharmaceutical company could 16 influence the opinion of these people. 17 Q Why? 18 A Because these are 19 independent academics who have an obligation, not 20 to the pharmaceutical industry, but to the German 21 government. 22 Q Then why would you be 23 contacting them if they're supposedly independent? 24 A To find information 275 1 regarding the basis of their decision. 2 Q Why not write them? 3 A I'm not sure that they 4 weren't written to; this doesn't tell me whether 5 they were -- oh, I guess it says visitation. 6 Q Yes. 7 A You would have to ask the 8 people who were involved why they chose to 9 personally visit as opposed to write or phone 10 call. 11 Q Have you seen anything in 12 writing concerning any visitation? 13 A No, because -- I may well 14 have, I'll correct myself, but I don't know who 15 the members of Commission A are, so I couldn't 16 comment on whether I have seen anything 17 specifically. 18 Q The last paragraph of 19 this document says, "It is our intention to review 20 all appropriate communication channels prior to 21 the official response by the BGA." Is it your 22 testimony that you don't read that as an intent to 23 influence members of the commission? 24 A Yes, that is my 276 1 testimony. 2 Q Also as part of the 3 action plan, Doctor Weber and others suggest that 4 Lilly should identify the possible legal 5 alternatives and timing implications that may be 6 encountered with the BGA on fluoxetine. Do you 7 know of any legal alternatives that were 8 discussed? 9 A I was not involved in any 10 discussion of legal alternatives. 11 Q Do you know of any legal 12 alternatives that could have been brought to bear 13 or reviewed in connection with BGA action? 14 A No, I'm not familiar with 15 what the legal alternatives are for Germany. 16 Q Well, we know that 17 Mr. Straeter, the former head lawyer with the BGA, 18 was consulted by Lilly, don't we? 19 A He was consulted by 20 Lilly, yes. 21 Q And he, in fact, took the 22 diskette to Berlin to the BGA, didn't he, once 23 approval was secured? 24 A That was approximately 277 1 four years later, so I'm not sure that I see any 2 particular connection. He took the diskette in 3 1989, I believe, and as I testified yesterday, he 4 was simply asked to deliver the diskette, and that 5 to me in no way denotes any kind of attempt to 6 influence. 7 Q I didn't suggest that 8 that did, I just -- it is a fact that Mr. Straeter 9 was formerly the head lawyer with the BGA, or was 10 he at the time in December of '89, or do you know? 11 A He was not the head 12 lawyer of the BGA from 1989, no. 13 Q The final point on the 14 action plan suggests that Lilly should, quote, 15 "Determine the BGA actions initiated towards 16 Duphar during their product review submission," 17 correct? 18 A Correct. 19 Q What is Duphar? 20 A A pharmaceutical company. 21 Q In Germany? 22 A It's a European company 23 that does business, I think, in many countries, 24 including Germany. 278 1 Q Do you know what BGA 2 actions were initiated towards Duphar during the 3 product review of whatever product it was they had 4 under submission? 5 A No. 6 Q Do you know whether or 7 not Duphar did, at the time, manufacture an 8 antidepressant? 9 A I believe they did. 10 Q What was the name of that 11 antidepressant? 12 A I believe it was 13 Fluvoxamine. 14 Q Is that a specific 15 serotonin reuptake inhibitor? 16 A I don't think so. I'm 17 not very familiar with the drug, but I don't 18 believe that it is a specific serotonin reuptake 19 inhibitor. 20 Q But it is an 21 antidepressant? 22 A Yes. 23 Q Look at Exhibit 9 again, 24 Doctor Weinstein. 279 1 A Uh-huh. 2 Q As you'll recall 3 yesterday, we discussed this exhibit and you said 4 you were having a little bit of difficulty 5 responding to my questions concerning what expert 6 documents you had seen and what expert suicide 7 opinions you had reviewed in connection with the 8 BGA, and that you would need to know the names or 9 need to see a copy of the document that was not 10 redacted such as this document, correct? 11 A Correct. 12 Q Have you seen such a 13 document? 14 A No. 15 MR. SMITH: Counsel -- 16 MR. FREEMEN: We hope to 17 have it over here in the next few minutes. We 18 asked them to make a search for the records and 19 they have found the document and are going to fax 20 it. 21 MR. SMITH: Very good. 22 Q (BY MR. SMITH) Now, 23 approval was granted in December of 1989 by the 24 BGA, correct? 280 1 A Correct. 2 Q In Exhibit 14, there is 3 discussion on the third page of Exhibit 14 that 4 there would be an appeal or a possible appeal 5 concerning wording in the package insert, correct? 6 A I don't have Exhibit 14. 7 (TENDERED.) 8 Q The third page. 9 A Uh-huh. 10 Q That's the fall of the 11 Berlin Wall page. 12 A Yes. 13 Q And it indicates that 14 there is a possible appeal that's going to be 15 taken in connection with the wording of the 16 package insert, right? 17 A Correct. 18 Q Do you know if an appeal 19 was taken? 20 A No. 21 Q You say you don't know or 22 there was no appeal taken? 23 A I don't know. 24 Q Who would know that? 281 1 A Doctor Weber would know. 2 Q Do you know of anybody in 3 Indianapolis that would know that? 4 A No, I can't think of 5 anybody here who would know that. 6 Q Are you aware of any 7 changes in the wording of the package literature 8 or prescribing information that was originally 9 required in Germany, under the original approval, 10 up to this date? 11 A I'm aware that since the 12 approval of fluoxetine there have been a number of 13 changes in the package insert that have gone on 14 worldwide. 15 Q How about Germany? 16 A My assumption is that 17 Germany, like every other country, has made these 18 package insert changes. 19 Q Have there been changes 20 in those portions of the package insert and 21 product prescribing information in connection with 22 risk of suicide or concomitant use of 23 tranquilizers in certain patients? 24 A There may well have been, 282 1 I am not personally involved in that. I know that 2 as with all products, as greater experience is 3 gained, there are changes that are made in the 4 package literature. Those are done by Lilly on a 5 global basis everywhere we market the drug, but 6 I'm not familiar with the specifics related to 7 fluoxetine. 8 Q Well, we know that the 9 package insert continued to have the language as 10 of March 1992, as reflected by Exhibit 11, don't 11 we? If you look at the last page, I think it's 12 dated. 13 A Could you repeat the 14 question, please? 15 REPORTER: (READING) Well, 16 we know that the package insert continued to have 17 the language as of March 1992, as reflected by 18 Exhibit 11, don't we? 19 A Could you define what 20 kind of language you're talking about? 21 Q The language of my 22 previous question concerning risk patients, risk 23 of suicide, and the necessity of additional 24 sedatives in particular instances. 283 1 MR. FREEMAN: Not 2 necessity now. 3 MR. SMITH: It says 4 taking an additional sedative may be necessary. 5 MR. FREEMAN: May be 6 necessary. 7 MS. ZETTLER: And he said 8 in particular cases. 9 MR. SMITH: I said 10 necessity in particular cases. 11 A It does say that 12 sedatives may be necessary. 13 Q And that was contained in 14 the language, at least in March 1992, wasn't it? 15 A Correct. 16 Q Do you know of any 17 changes that have been made since March 1992 under 18 the risk patients category? 19 A I don't know of any. 20 Q Do you know of any appeal 21 that was taken concerning any product information 22 documents in Germany subsequent to March 16, 1992, 23 the date of Exhibit 11? 24 A When you say -- could you 284 1 define what you mean by appeal? 2 Q Appeal as was mentioned 3 in the letter advising of the acceptance of Prozac 4 in Germany. 5 A Could you clarify? 6 You're asking me if -- 7 Q Look on Page 3. 8 A I see Page 3, but you're 9 asking me if an appeal mentioned in 1989 was taken 10 subsequent to March 1992? 11 Q An appeal similar to that 12 mentioned in 1989 was taken after March 16, 1992. 13 A I have no knowledge of 14 that. 15 Q So as far as you know, 16 the product prescribing information, or the 17 information concerning use reflected in Exhibit 18 11, continues to be the same today? 19 A I don't think I said 20 that. I think what I said was that I know that 21 there have been a number of package insert 22 literature changes made with fluoxetine on a 23 global basis. It is very possible that there were 24 changes made subsequent to March 1992, but I would 285 1 not have been involved in those decisions and 2 would not be aware of that. 3 Q So it's possible there 4 have not been any changes, since you wouldn't be 5 aware of it? 6 A It's possible that there 7 would or would not be changes, that's correct. 8 Q You just don't know? 9 A I don't know. 10 Q Is it your testimony here 11 today that all of the package inserts globally in 12 connection with fluoxetine hydrochloride are the 13 same, other than this German package insert? 14 A No. 15 (WEINSTEIN EXHIBIT NO. 16 MARKED FOR 16 IDENTIFICATION.) 17 Q Exhibit 16 is a document 18 dated December 6, 1990, one at 8:06 in the morning 19 and the other at 12:03, correct? 20 A Correct. 21 Q I guess the one on the 22 bottom of Page 1 of the exhibit is the first part 23 of it, is that correct? 24 A Correct. 286 1 Q The subject of the 2 document is "Fluoxetine/BGA", correct? 3 A Correct. 4 Q It's authored by Hans 5 Weber? 6 A Correct. 7 Q And you're copied in? 8 A Yes. 9 Q It's directed to Robert 10 G. Thompson? 11 A Correct. 12 Q Who was Robert G. 13 Thompson at the time? 14 A A physician who at the 15 time was called an international medical advisor. 16 Q Did he work in 17 Indianapolis? 18 A In Indianapolis. 19 Q How did his 20 responsibilities differ from yours? 21 A He reported to me. 22 Q And what did his duties 23 include? 24 A It included worldwide 287 1 responsibility, excluding the United States, for a 2 certain number of Lilly compounds on the 3 medical -- with regard to medical aspects. 4 Q Was he a medical monitor 5 of clinical trials? 6 A No. 7 Q International? 8 A No. 9 Q Did he have anything to 10 do with coordinating clinical trials? 11 A He had to do with 12 coordinating clinical trials, but he was not the 13 specific monitor. 14 Q Was he sort of -- I don't 15 want to use the term assistant, but did he 16 interface with you in connection with your duties? 17 A Yes. 18 Q He helped you -- 19 A Yes. 20 Q -- in doing your duties? 21 A Correct. 22 Q Did you have anyone else 23 that performed the same job function as Doctor 24 Thompson? 288 1 A Yes, there were other 2 people. 3 Q All right. And Thompson 4 is an MD? 5 A Yes. 6 Q What other MD's assisted 7 you in this, let's say in December 1990? 8 A I would have to go back 9 to my records. There are other MD's, but they 10 changed frequently and I don't recall who 11 specifically was there in December 1990. 12 Q All right. But you 13 normally had more than one medical doctor 14 assisting you in accomplishing your duties? 15 A Yes. 16 Q Can you give me the names 17 of somebody that you recall -- some others that 18 you recall assisting you in connection with 19 Prozac? 20 A Doctor Thompson was the 21 only one who assisted me in regards to Prozac. 22 Q All right. The document 23 states, "In order to reply to the BGA letter, we 24 propose the following strategy: 1. Spontaneous 289 1 reports on suicides, suicide attempts, violent 2 behavior from Germany." Does it state that? 3 A Yes. 4 Q Now, this is a year after 5 approval has been granted in Germany, correct? 6 A Correct. 7 Q Do you know what letter 8 from the BGA this is that is being referred to in 9 Exhibit 16? 10 A No. 11 Q Did the BGA make some 12 further inquiries specifically regarding suicides 13 after Prozac was approved in Germany? 14 A I don't know what the 15 letter -- I don't recall the letter, so I can't 16 really characterize what they did. 17 Q Well, the term suicide is 18 used about two hundred and eighty-seven different 19 times further on in this document, isn't it? 20 A Probably somewhat less 21 than two hundred and eighty-seven, but it is used 22 frequently. 23 Q Okay, I exaggerated. 24 This is the first time I've ever exaggerated, 290 1 Doctor, in any deposition. The fact is, though, 2 Doctor, that the entire response plan is in 3 connection with the issues of suicidality and 4 violent aggressive behavior, isn't it? 5 A Yes. 6 Q It appears that all the 7 information was being secured in response to the 8 BGA letter concerning those issues, correct? 9 A Correct. 10 Q So do you recall why 11 there was -- even though you don't recall 12 specifically what the letter was, why there was 13 this effort to secure all this information on 14 suicides and violent aggressive behavior a year 15 after the product had been approved in Germany? 16 A I don't recall the 17 specific reason why the BGA would have written a 18 letter at this time. 19 Q It appears that the 20 strategy is to provide the BGA spontaneous reports 21 on suicides, suicide attempts and violent behavior 22 that had occurred in Germany, correct? 23 A That's one of the pieces 24 of information that would be -- 291 1 Q It's Item 1? 2 A Item 1. 3 Q Did the German BGA not 4 require that you report to them instances when 5 this occurred within a certain prescribed period 6 of time? 7 A I'm not sure that I 8 understand the question. 9 Q Well, if an adverse event 10 occurs in the United States under certain 11 circumstances, in connection with certain acts, 12 the United States Food and Drug Administration 13 requires that the manufacturer notify them in a 14 certain specified time, correct? 15 A Correct. 16 Q And that's what I'm 17 asking you, is didn't Germany have requirements 18 similar to that? 19 A Yes. 20 Q So wouldn't Germany have 21 already had this information? 22 A They may well -- the 23 German government? 24 Q Yes, the BGA. 292 1 A They may well have. 2 Q Then why were these items 3 being collected again? 4 A My interpretation of 5 Point 1 is not that they're only being collected 6 again, but there is a detailed analysis that is 7 being done that involves detailed review of 8 individual cases, a pharmacoepidemiologic 9 assessment of those cases, and outside expert 10 opinion regarding those cases. So, it would not 11 be surprising at all to me that the same cases 12 that the BGA had already received would be 13 received again with this added analysis. 14 Q Have you ever seen that 15 added analysis? 16 A No. 17 Q Why not? 18 A It would not be necessary 19 for me to see it. 20 Q Who would have prepared 21 that analysis? 22 A Lilly Germany. 23 Q Item C under Point 1 says 24 outside expert opinion and lists two professors 293 1 there, doesn't it? 2 A Yes. 3 Q Have you ever seen that? 4 A No. 5 Q Do you know who the 6 experts were that are referred to in Point C? 7 A No. 8 Q Under Point 3, Item C 9 asks in connection with violent behavior, would it 10 be possible to get violent behavior analysis from 11 studies from the US? 12 A Correct. 13 Q Do you know if there was 14 a violent behavior analysis done on US studies? 15 A I don't specifically 16 know. I see the request here, but I don't know 17 what the follow-up was. 18 Q Under Point 5, Summary 19 and Conclusions, the second paragraph reads, 20 quote, "I realize that analysis of violent 21 behavior may be one of the issues. Suicidality 22 certainly has priority. Please let us know what 23 you think about this strategy, whether you're able 24 to provide the data and any other advice," end 294 1 quote, correct? 2 A Correct. 3 Q Before this December 4 1990, were you aware that there was a question 5 concerning a relationship between Prozac and 6 violent behavior? 7 A I must admit I'm somewhat 8 vague on dates, and the only way I could answer 9 that is to say I don't recall whether before 10 December 1990 was the time that there were various 11 newspaper articles in this country referring to 12 that issue, and if, in fact, those had been 13 written before December 1990, then I was aware. 14 Q Well, is it your 15 testimony, Doctor, that as the international -- 16 well, in 1990 you would have been the vice 17 president of international medical affairs at Eli 18 Lilly. Is it your testimony at that time that you 19 first learned of any possible question concerning 20 Prozac and violent aggressive behavior in the 21 newspaper publications? 22 A I'll revise that only to 23 say it was either the newspaper or television, 24 correct. 295 1 Q You didn't see any 2 concern about that through any scientific body? 3 A No. 4 Q Do you know if there's 5 been any analysis of whether there's a connection 6 between Prozac and violent aggressive behavior? 7 A I believe that people 8 were working on such an analysis, but I did not 9 see it and have not been involved in that area. 10 Q Who was working on that 11 analysis? 12 A I don't know the specific 13 individuals; it was people involved with Prozac. 14 MR. FREEMAN: What's the 15 date of that document? 16 MR. SMITH: August 3, 17 1990. 18 (WEINSTEIN EXHIBIT NO. 17 MARKED FOR 19 IDENTIFICATION.) 20 Q (BY MR. SMITH) Doctor 21 Weinstein, Exhibit 17 is a document dated August 22 3, 1990, authored by a Mr. Keitz? 23 A Ms. von Keitz, yes. 24 Q And you are copied on 296 1 that, correct? 2 A Correct. 3 Q And it's entitled 4 "Suicide Report for BGA", and says, "Attached is 5 the report on suicides and suicide attempts, which 6 we submitted to the BGA in December 1986," 7 correct? 8 A Correct. 9 Q Do you know why she was 10 sending that report to Doctor Thompson in August 11 of 1990? 12 A No. 13 Q Eight or nine months 14 after the product was approved in Germany? 15 A No, I don't know the 16 specific reason. 17 Q And Page 2 indicates that 18 the cutoff date for the data reflected in the 19 report was August 31, 1986, does it not? 20 A Correct. 21 Q In the first two pages of 22 the report itself is a summary of the graphic data 23 presented throughout the report, correct? 24 A Correct. 297 1 Q On Page 2 of the summary, 2 the third paragraph, it says, "In France, 3 seventeen of eighteen suicide deaths have been 4 reported during a six months uncontrolled 5 treatment with fluoxetine. The incident rate is 6 about ten times higher compared to US data 7 reflecting a different group of patients and kind 8 of follow up," correct? 9 A Correct. 10 Q Do you read that 11 paragraph -- that I assume was authored by Doctor 12 Schulze-Solce, right? 13 A Correct. 14 Q Do you read that 15 paragraph to indicate that the reason for this 16 finding in France of a higher -- a ten times 17 higher incident rate of suicidal gestures was 18 because of a different group of patients and a 19 different follow-up than that in the United 20 States? 21 A Those are the words. 22 Since the group of patients is not defined and the 23 kind of follow-up is not defined, I don't know 24 what the differences are that he's referring to, 298 1 but those are the words he uses. 2 Q I guess maybe you've 3 answered my next two questions, which is do you 4 know any difference in the patients in the 5 fluoxetine trials in the France as opposed to that 6 of the United States? 7 A I'm not familiar with the 8 details of the fluoxetine trials in France, so I 9 really can't comment. 10 Q Well, have you ever seen 11 any analysis of any difference in the type of 12 patients? 13 A It is certainly possible 14 that -- as I mentioned yesterday, that different 15 rating scales and different approaches to 16 depression may occur in France as opposed to the 17 US, and that his statement may reflect some of 18 that difference, but I cannot speculate on what 19 specifically he's talking about. 20 Q Is there any evidence 21 that you've ever seen, Doctor Weinstein, of people 22 of a particular country having a higher incidence 23 of suicides or attempted suicides than those of 24 another country? 299 1 A I've not seen information 2 that would either confirm or deny that suggestion, 3 I don't know. 4 Q In other words, you've 5 indicated -- you indicated yesterday that there 6 were different types of rating scales in 7 connection with depression used in different 8 countries, is that correct? 9 A Correct. 10 Q During the clinical 11 trials? 12 A Correct. 13 Q But my question is, an 14 attempted suicide is an attempted suicide, 15 correct? 16 A Correct. 17 Q So how does the different 18 rating scales affect any data concerning attempted 19 suicide or completed suicide? 20 A I didn't suggest that 21 there was any link between those facts; I simply 22 said that there are different rating scales and 23 different approaches to the practice of psychiatry 24 and medicine in different countries. 300 1 Q But if an individual 2 attempted suicide in France and an individual 3 attempted suicide in the United States, they would 4 both basically be the same, quote, kind of 5 patient, in that they had both attempted suicide? 6 A They both would have 7 attempted suicide, yes. 8 Q And the country in which 9 they were residing at the time doesn't have any 10 relation to whether or not they attempted suicide, 11 does it? 12 A No. 13 Q Is there any 14 difference -- it speaks here in terms of a 15 different kind of follow-up, correct? 16 A Correct. 17 Q Do you know of any 18 difference in follow-up between the United States 19 and France that makes it more likely that 20 individuals will attempt suicide in France than in 21 the United States? 22 A I can't comment because I 23 don't know the design of the study and I don't 24 know the design of the follow-up, so I can't 301 1 comment on any of the results or suggestions that 2 are mentioned in this paragraph. 3 Q Can you think of any 4 difference in kind of follow-up that would reflect 5 a difference in attempted suicide? 6 A I would defer, frankly, 7 to a psychiatrist who would know better. 8 Different studies designed in different ways, 9 particularly in terms of the length of observation 10 or other factors, might have different findings, 11 but I can't comment on this because I'm not aware 12 of the design of the studies in France. 13 Q But these were Lilly 14 clinical trials that they're speaking of? 15 A That's correct. 16 Q And just a difference in 17 the location where the clinical trial is 18 occurring, correct? 19 A Correct. 20 Q And whatever follow-up 21 these patients are receiving, it's follow-up as 22 prescribed by a Lilly protocol, isn't it? 23 A Correct. 24 Q And theoretically these 302 1 patients are under the medical care of a Lilly 2 investigator, are they not? 3 A They are under the care 4 of an investigator whose study is being supported 5 by Lilly, that's correct. 6 Q Well, the investigators 7 are providing medical psychiatric care to the 8 members of the trial, are they not? 9 A Correct. 10 Q And they're being paid on 11 a patient-by-patient basis for that care by Lilly, 12 are they not? 13 A Correct. 14 Q And certainly the intent 15 of Lilly in drawing up the protocol and in 16 selecting the investigators is that the patients 17 who are part of the trial get good medical care, 18 is it not? 19 A Correct. 20 Q So have you ever seen any 21 criticism of the follow-up care by Lilly 22 investigators that would account for a higher rate 23 of suicide, ten times greater rate in France than 24 in the United States? 303 1 A No, I have not seen any 2 criticism of the care given by Lilly 3 investigators. 4 Q So can you give me any 5 explanation as to why Doctor Schulze would be 6 making these statements that, quote, "The incident 7 rate is about ten times higher compared to US data 8 reflecting a different group of patients and kind 9 of follow-up"? 10 A No, I cannot give you an 11 explanation. 12 Q I beg your pardon? 13 A I cannot give you an 14 explanation. 15 Q The graphs that are 16 appended to Exhibit 17, the suicide reports 17 submitted to the BGA, have a term "patient years", 18 do they not? 19 A Yes. 20 Q Do you know what a 21 patient year is? 22 A I could only guess and 23 tell you that it may reflect a multiplication of 24 the number of patients who had received the drug 304 1 times the time they had received the drug, to 2 create a number which is occasionally used in 3 scientific analysis, which is patient year. So if 4 three patients had each received the drug for one 5 year, there would have been three patient years' 6 experience with the drug, any drug, and it is one 7 way of statistically analyzing information. 8 Q Of course, the vast 9 majority of the patients in the Prozac clinical 10 trial didn't get the drug anywhere close to a 11 year, did they? 12 A No. 13 Q Are you, by your answer, 14 indicating agreement with my statement or 15 disagreement? 16 A I agree. 17 Q So how could you get a 18 patient year in a patient that had only been 19 taking the product for six or eight weeks, as is 20 prescribed by some of the protocols on the Prozac 21 clinical trials? 22 A It is possible to use 23 fractions, and so if the patient received the drug 24 for eight weeks, that is eight out of fifty-two 305 1 weeks, and one can say that the patient received 2 the drug for eight fifty-seconds of a year, and in 3 fact that is a very common use in scientific 4 analysis. 5 Q All right. Look with me 6 at Table 1 of that group, do you see that? 7 A Yes. 8 Q It says "Worldwide 9 Total", correct? 10 A Correct. 11 Q It says there were six 12 thousand -- and I'm having a little difficulty 13 reading this because of the stamp, is it six 14 thousand, nine hundred and three? 15 A I believe so, yes. 16 Q Are you having difficulty 17 reading this because of the stamp? 18 A No, my wonderful eyesight 19 with magnification has allowed me to read this 20 with great clarity. 21 Q Six thousand, nine 22 hundred and three or ninety-three patients on 23 Prozac? 24 A I believe it's six 306 1 thousand, nine hundred and three. 2 Q All right. So that was 3 the total number of patients who were exposed to 4 Prozac, correct? 5 A At that time. 6 Q Yes, sir. 7 A As of, I believe, the end 8 of August; August 31, 1986. 9 Q Then under that it has 10 patients years, on Table 1, one thousand, one 11 hundred and sixty-eight; is that right? 12 A Correct. 13 Q Do you know how that 14 patient year figure was calculated? 15 A I presume, as I suggested 16 earlier, that the number of six thousand, nine 17 hundred and three was multiplied by the average 18 duration of therapy of those six thousand, nine 19 hundred and three, which clearly is about one- 20 sixth of a year, which is about eight weeks, then 21 one would come up with the patient year of one 22 thousand, one hundred and sixty-eight. 23 Q Why do you want to get a 24 patient year figure? 307 1 A That is a standard method 2 that is used to look at the incidence of disease, 3 to look at the incidence of complications of 4 disease. That is used worldwide by scientists and 5 epidemiologists and governments to look at 6 incidence of medical phenomena, including such 7 organizations as the World Health Organization. 8 It is standard convention. 9 Q I'm not criticizing that. 10 A I'm trying to help you 11 understand what the numbers mean. 12 Q I'm just asking you the 13 reason for that. But it certainly does not imply 14 that any patient has been on the drug for one 15 thousand, one hundred and sixty-six years, 16 correct? 17 A If that is the case, I 18 think we all should take the drug. 19 Q Or either it ought to be 20 marketed for another indication. In that 21 worldwide total document, it indicates that there 22 was nine successful suicides on those people 23 taking Prozac, correct? 24 A Correct. 308 1 Q While there was three on 2 others? 3 A Correct. 4 Q And here it also 5 includes, under other, there is an asterisk, is 6 there not? 7 A Yes. 8 Q If you go down, it looks 9 like the asterisk says other would include 10 placebo, no drug, or comparator, does it not? 11 A Correct. 12 Q Do you know why all of 13 those terms were lumped together? 14 A No, I don't specifically 15 know the reason why they were lumped together. 16 Q That doesn't give you any 17 analysis, does it, of a comparison of relative 18 incidence of suicide between Prozac and the other 19 antidepressants, does it? 20 A No, this would not. 21 Q And it doesn't give you 22 an analysis of the incidence of suicide of people 23 on Prozac versus placebo, does it? 24 A No. 309 1 Q And I would assume that 2 where they've used the term no drug, would that 3 have to be a situation where a patient 4 discontinued the medication or there was some 5 compassionate use protocol or something? 6 A I don't know what that 7 means. My supposition would be that there were 8 trials done in which a placebo capsule was not 9 given and the patient was simply observed without 10 any form of therapy, but -- I think that's one 11 possible explanation. 12 Q You mean they might be 13 comparing Prozac, an individual taking Prozac, to 14 an individual that wasn't even being given a 15 placebo? 16 A That's a possibility. 17 Q Well, how would that 18 occur? 19 MR. FREEMAN: Simply 20 psychotherapy. 21 A It could occur in the 22 course of normal practice. 23 Q So you might have an 24 investigator that was including comparator data on 310 1 a patient that he was just seeing there for 2 psychotherapy, on a patient that wouldn't even 3 have been enrolled in a clinical trial? 4 A The patient could have 5 been enrolled in a clinical trial and not received 6 therapy because the comparative agent could have 7 been psychotherapy, nonpharmacologic therapy. 8 Q Do you know of any 9 protocols that call for such a study? 10 A No. 11 Q Do you have a scientific 12 opinion on whether or not a protocol of that 13 nature would be of any benefit whatsoever in 14 examining the effect of a drug under 15 investigation? 16 A I have a scientific 17 opinion that since psychotherapy is an accepted 18 form of therapy for psychiatric diseases, that it 19 would not necessarily be inappropriate to compare 20 pharmacologic therapy to psychotherapy. 21 Q You say it would not 22 necessarily be inappropriate? 23 A It would be appropriate. 24 It would be appropriate. 311 1 Q Well, do you know of any 2 studies Lilly has ever done in connection with 3 Prozac, fluoxetine hydrochloride, for any 4 indication in which that was done? 5 A No, but I'm not familiar 6 with all of the studies Lilly has done. 7 Q Who would know that? 8 A I suggest that people who 9 put this document together in Germany would 10 probably be able to provide you with information 11 about how they put the document together and what 12 data sources they utilized. 13 Q Have there been any cost 14 effectiveness studies done where there was an 15 analysis of the difference in cost of using Prozac 16 in lieu of or compared to psychotherapy? 17 A I'm not aware of any. 18 Q None that you know of as 19 international medical director have been done by 20 Lilly? 21 A I'm not aware that any 22 have been done, that's correct. 23 Q This document indicates 24 that there were fifty-four patients on Prozac who 312 1 attempted suicide up to that date in time? 2 A Correct. 3 Q And that there were 4 twelve who were on others who attempted suicide? 5 A Correct. 6 Q Be that placebo, 7 comparator, or no drug? 8 A Correct. 9 Q But we don't know whether 10 that twelve there is people on a comparator, or 11 all people on comparators, or people on placebo, 12 or all people on placebo, or people that didn't 13 have any drug therapy whatsoever, correct? 14 A Correct. 15 Q Have you ever seen an 16 analysis of any potential connection between 17 Prozac and violent aggressive behavior or 18 suicidality that lumped comparator figures of 19 placebo, no drug, and comparator drugs, to make 20 the comparison between Prozac? 21 A No. 22 MR. SMITH: Let's take a 23 break. 24 (SHORT BREAK TAKEN.) 313 1 (WEINSTEIN EXHIBIT NO. 18 MARKED FOR 2 IDENTIFICATION.) 3 Q (BY MR. SMITH) Doctor, 4 Exhibit 18 is apparently more follow-up work in 5 connection with the German Prozac issues that had 6 been discussed earlier, approximately a year after 7 the product was approved in Germany, correct? 8 A Correct. 9 Q You are an addressee of 10 that document, are you not? 11 A Correct. 12 Q It's dated December 7, 13 1990, correct? 14 A Correct. 15 Q Under the bullet point 16 "German affiliate efforts", do you see that, 17 Point 1? 18 A Yes. 19 Q Point 1, then bullet 20 point under that? 21 A Yes. 22 Q It says, "German 23 affiliate efforts - They have reviewed their 24 depression clinical trial data which was gathered 314 1 during the recent US CRA/CIR visit. They have not 2 had physicians review the information and thus 3 would prefer that our physicians (Charles and 4 John) review the data," correct? 5 A Correct. 6 Q Do you know why the 7 affiliate was requesting that this data be 8 reviewed in Indianapolis by Charles Beasley and 9 John Heiligenstein as opposed to physicians in 10 Germany? 11 A No. 12 Q Then under "Spontaneous 13 reports", Point 2, it indicates: "Spontaneous 14 reports - These are being reviewed by the German 15 affiliate and will not be presented to outside 16 opinion leaders," correct? 17 A Correct. 18 Q Do you know why this 19 spontaneous report data was not submitted to 20 outside opinion leaders? 21 A No. 22 Q Obviously, then, any 23 opinion of an outside opinion leader reflective of 24 this data would not include the spontaneous 315 1 reports, correct? 2 A Correct. 3 Q Do you know if the 4 spontaneous report data is referring to 5 spontaneous reports in Germany alone or all 6 spontaneous reports concerning adverse events in 7 connection with Prozac, I assume toward the issue 8 of suicidality? 9 A I don't know what 10 spontaneous reports it's referring to. 11 Q Well, under that it says, 12 "Hans would like to have updated reports of US 13 and international events (summary graphs and 14 tables) and a possible denominator regarding 15 estimated use. The update should be through 16 November 30, if possible," correct? 17 A Correct. 18 Q That indicates to me that 19 the spontaneous reports is going to include all 20 spontaneous reports, updated through November 30, 21 correct? 22 A That certainly is a way 23 of interpreting it, yes. 24 Q Is it a reasonable way of 316 1 interpreting it, Doctor? 2 A It's a reasonable way. 3 Q Beg your pardon? 4 A It's a reasonable way of 5 interpreting it. 6 Q Then Point 3 says, "CIOMS 7 issue - this is being discussed independently by 8 Max, Allan, Leigh and others," correct? 9 A Correct. 10 Q I assume that Allan is 11 referring to you? 12 A Correct. 13 Q Do you recall discussing 14 the CIOMS issue with Max Talbott and Leigh 15 Thompson now? 16 A No, I don't know what 17 issue to which this is referring. 18 Q Do you know what the 19 CIOMS is, C-I-O-M-S? 20 A C-I-O-M-S is actually the 21 initials of a group that is attempting to work on 22 adverse drug reporting on a global basis to 23 standardize procedures of the various countries. 24 Q Do you remember this 317 1 discussion? 2 A No. 3 Q Do you know what the 4 CIOMS issue was? 5 A No. 6 Q All right. Back to 7 Exhibit 9. We've been provided by counsel an 8 unredacted version of Exhibit 9. Have you had an 9 opportunity to see it yet? 10 A Yes. 11 Q Does that help you, 12 seeing the unredacted version, in answering those 13 questions that we presented to you yesterday 14 concerning the expert opinions? 15 A In seeing the unredacted 16 version, I recall that the names mentioned there 17 are experts in the area of phospholipidosis. 18 Q Well, it says concerning 19 expert opinions in general, we may mention that we 20 already have in house fluoxetine in general, 21 according to the list of concerns by BGA, two 22 expert opinions. Then it lists Benkert, Mainz and 23 Heimann, right, and Tuebingen? 24 A Can I look at that 318 1 again? I looked primarily at Point 2 rather -- 2 Q Yes, I think that's why I 3 was trying to help you. 4 A I would only say that I 5 don't know who these people are. Mainz is the 6 name of a city and Tuebingen is the name of a 7 city, so the experts are Benkert and Heimann, and 8 I don't have any specific familiarity with either 9 one of them. 10 Q So you don't intend to 11 limit your answer that they are experts on 12 phospholipidosis, do you? 13 A I was incorrect; I was 14 referring to the second paragraph of the first 15 redacted or unredacted point where I read the 16 names Luellmann, von Wichert, Thiel, and then 17 again in the second redacted point, Luellmann and 18 von Wichert, and those are, in fact, experts in 19 phospholipidosis. 20 In reading the other now 21 unredacted piece, which I neglected to read when I 22 first saw this, I know -- I assume that these are 23 experts in suicide, but I'm not sure of that, and 24 I recognize that Mainz and Tuebingen are cities in 319 1 Germany, but I don't know the individuals 2 involved. 3 Q But they're at least 4 listed as suicide experts, are they not, even 5 though you don't have any independent knowledge 6 that they're suicide experts? 7 A No, actually they're 8 not -- not those two. The other ones who are 9 listed as suicide experts are Pohlmeier and 10 Winzenried, and since they are listed as suicide 11 experts by the associate medical director in 12 Germany, I have to accept his characterization. 13 Q Have you ever seen 14 reports from those gentlemen? 15 A No. 16 Q The document does state, 17 though, that English translations were supplied to 18 Indianapolis of those reports? 19 A Correct. 20 Q And that those expert 21 opinions were sent to Doctor Wernicke? 22 A Correct. 23 MR. SMITH: Why don't we, 24 for completeness, add this unredacted version as 320 1 an exhibit. 2 MR. MYERS: That's fine, 3 make it 9A or something. 4 MR. FREEMAN: I thought 5 you had already marked it, you had not? 6 MS. ZETTLER: Why don't 7 you staple it to 9. 8 MR. MYERS: We'll just 9 designate it as confidential, maybe, when we 10 review the transcript. If that's all right with 11 you, that's okay with us. 12 MR. SMITH: I just wanted 13 to make sure you knew that it didn't have the 14 stamp on it. 15 MR. MYERS: Thank you. 16 (WEINSTEIN EXHIBIT NO. 9A MARKED FOR 17 IDENTIFICATION.) 18 (WEINSTEIN EXHIBIT NO. 19 MARKED FOR 19 IDENTIFICATION.) 20 Q (BY MR. SMITH) Exhibit 21 19 is another document out of Germany about this 22 same time, specifically November 13, 1990, isn't 23 it? 24 A Correct. 321 1 Q And it is authored by 2 Claude Bouchy and is directed to Doctor Leigh 3 Thompson, yourself, and Doctor Robert Zerbe, is it 4 not? 5 A Correct. 6 Q And it concerns adverse 7 drug event reporting with respect to Prozac 8 suicides, does it not? 9 A Correct. 10 Q The first paragraph says, 11 "Hans Weber and I have problems with the 12 directions our safety people are getting from the 13 corporate group (Drug Epidemiology Unit) and 14 requesting that we change the identification of 15 events as they are reported by physicians," 16 correct? 17 A Correct. 18 Q Do you know of any 19 instances in which any individual in the corporate 20 group, Drug Epidemiology Unit, were requiring or 21 requesting changes in adverse events that were 22 reported by physicians observing those events? 23 MR. FREEMAN: Read that 24 question back. 322 1 REPORTER: (READING) Do 2 you know of any instances in which any individual 3 in the corporate group, Drug Epidemiology Unit, 4 were requiring or requesting changes in adverse 5 events that were reported by physicians observing 6 those events? 7 MR. FREEMAN: That 8 document doesn't have a thing to do with that 9 subject matter, but go ahead and answer it. 10 A The answer is no. 11 Q Claude Bouchy points to a 12 specific instance next, does he not? 13 A Correct. 14 Q Where he says, quote, "On 15 this one, our safety staff is requested to change 16 the event term suicide attempt as reported by the 17 physician to overdose," correct? 18 A Correct. 19 Q Do you know of any 20 instances, other than this as reflected by Claude 21 Bouchy, in which there was a request that the term 22 suicide attempt as reported by the physician would 23 be changed to overdose? 24 MR. FREEMAN: Would you 323 1 clear this up for them, please? 2 A When an event is reported 3 to the company, the narrative that is described by 4 the physician, a physician's precise words are 5 transmitted to all government regulatory 6 agencies. At the request of the FDA and other 7 regulatory organizations, in addition to 8 transmitting the direct words of the treating 9 physician, they have requested that various terms 10 be classified into various headings. The FDA 11 event terminology, which has been adopted by 12 Lilly, the event -- the statement suicide attempt 13 maps to overdose as long as a drug was involved, 14 any drug. When suicide attempt is occurring and 15 there is no drug involved, it maps to the FDA 16 classification term depression. 17 What the FDA and the BGA 18 and the CSM and all regulatory agencies receive 19 worldwide is the event classified according to 20 this terminology and the original narrative by the 21 physician telling specifically, in his or her 22 words, what happened during the event. So, 23 there's no changing of the physician's words. 24 This is simply a classification system that has 324 1 been adopted by the FDA, there is a similar one 2 that has been adopted by the World Health 3 Organization, and it is a method that they use to 4 be able to classify events occurring with people 5 receiving drugs in a more systematic fashion than 6 they had been able to in the past. 7 Q Okay, now that you've 8 said that, I'm going to ask the court reporter to 9 go find my question again that I proposed to you. 10 A That's fine. 11 Q As opposed to what 12 Mr. Freemen proposed to you, and answer my 13 question. 14 REPORTER: (READING) 15 Question: Do you know of any instances, other 16 than this as reflected by Claude Bouchy, in which 17 there was a request that the term suicide attempt 18 as reported by the physician would be changed to 19 overdose? 20 MR. FREEMAN: I have an 21 objection to that. It misstates what the evidence 22 in the case is, as explained by the witness in the 23 response to the question. Go ahead and answer. 24 A The answer is no. 325 1 Q Well, the term suicide 2 attempt does not map to overdose, does it? 3 A It maps to overdose if 4 there was a drug involved. 5 Q What if there was not any 6 drug involved? 7 A It maps to depression. 8 Q And that's the subject of 9 Exhibit 19, isn't it? 10 A That's correct. 11 Q There's confusion there, 12 isn't there? 13 A Mr. Bouchy just does not 14 understand the event reporting system. As general 15 manager of Eli Lilly Germany, it's not terribly 16 surprising that he does not know all of the 17 details of the drug reporting system. 18 Q Well, it says Hans Weber 19 and I have problems with the directions our safety 20 people are getting. So apparently Hans Weber 21 doesn't understand either. 22 A He's just misinterpreted 23 what was told to his drug safety people. 24 Q How do you know that? 326 1 A Because his drug safety 2 people never would have been told to change the 3 physician's words, the narrative that is reported 4 to all regulatory agencies. 5 Q I don't think that that's 6 what he's saying. He says requesting that we 7 change the identification of events as they were 8 reported by physicians. 9 A And we do not do that. 10 Q Well, are you saying that 11 this statement made by Claude Bouchy and Hans 12 Weber is false? 13 A It is incorrect. 14 Q How do you know that? 15 You weren't there, were you? 16 A I know what the Lilly 17 reporting system is, and as I have described it to 18 you, we do not change the identification of events 19 as they are reported by the physician. 20 Q Well, you didn't hear any 21 direction that was received by the safety people 22 in Germany from the corporate group drug 23 epidemiology unit, did you? 24 A No, I did not hear -- 327 1 Q You are not even a member 2 of the drug epidemiology unit, are you? 3 A No. 4 Q Never were, were you? 5 A No. 6 Q So it's presumptuous on 7 your part to tell us here that you know what 8 instructions were being given by the drug 9 epidemiology unit to the safety individuals in 10 Germany, isn't it? 11 A No, I don't think it's 12 presumptuous. 13 Q Why? 14 A Because the rules that we 15 have in terms of drug safety monitoring and 16 adverse event reporting are very clearly 17 understood by all of our employees, and they would 18 not tell people to change physicians' words. I 19 have great faith in their honesty, and they would 20 not make such a recommendation. This is a 21 misinterpretation by Mr. Bouchy and Doctor Weber. 22 Q Obviously, these 23 instructions are not very well understood by 24 them. 328 1 A That may be the case; 2 however, they were not instructed to change words. 3 Q But you say that so 4 dogmatically when you don't know what the 5 instructions were, that's my problem with it, 6 Doctor Weinstein. You don't have any better idea 7 about that than anybody else, do you, because you 8 weren't a member of the drug epidemiology unit and 9 you weren't there within the safety group at 10 Germany, and you don't know what instructions were 11 given, do you? 12 A That's correct. 13 Q Now, what the document 14 says is, is that the safety people in Germany are 15 getting instructions or requests that the 16 individuals in Germany change the identification 17 of events as they were reported by the physician, 18 doesn't it? 19 A Those are the words, yes. 20 Q It doesn't say they were 21 getting instructions to change what was reported 22 by the physicians, it says they were getting 23 instructions to change the identification of 24 events, doesn't it? 329 1 A Correct. 2 Q So the implication isn't 3 there then that they were getting instructions to 4 change what the physicians said, is it? 5 A Correct. 6 Q All right. It says, "On 7 this one, our safety staff is requested to change 8 the event term 'suicide attempt' (as reported by 9 the physician) to overdose," is that correct? 10 A Correct. 11 Q On the other one, it was 12 requested that we change suicidal ideation to 13 depression, wasn't it? 14 A Correct. 15 Q It goes on to say, "Hans 16 has medical problems with these directions." Do 17 you assume that's problems as a medical doctor? 18 A That's a reasonable 19 assumption, yes. 20 Q And it goes on to say, "I 21 have great concerns about it. I do not think I 22 could explain to the BGA, to a judge, to a 23 reporter or even to my family why we would do this 24 especially on the sensitive issue of suicide and 330 1 suicide ideation. At least not with the 2 explanations that have been given to our staff so 3 far. I am quoting, 'When an overdose is taken in 4 a suicide attempt, our Research Physicians prefer 5 to list the event term overdose' even if when 6 tracking suicides, we always look at all overdose 7 and suicide attempt reports'," correct? 8 A Correct. 9 Q So it appears to me from 10 reading this that Mr. Bouchy and Doctor Weber 11 understand the instructions, but just disagree 12 with the characterizations? 13 A I don't agree with that 14 interpretation. 15 Q What's your 16 interpretation? 17 A That they don't 18 understand the instructions. 19 Q Well, they go on to 20 specify what instructions they're being given, 21 don't they? 22 A Yes. 23 Q Bouchy goes on to say, 24 "This issue has been argued back and forth for 331 1 about a month between Bad Homburg and Indy, 2 therefore I am bringing it to your attention and 3 await your directions," correct? 4 A Correct. 5 Q So, obviously, it sounds 6 to me like there has been a considerable amount of 7 discussion between them and Indy concerning this. 8 A There certainly has been 9 discussion; I don't know how frequent the 10 discussions were, but there have been discussion. 11 Q Because you didn't have 12 anything to do with those discussions, did you, 13 Doctor Weinstein? 14 A That's correct. 15 Q So you don't know who is 16 confused and who is not confused, really, do you? 17 A I disagree with that. 18 Q Well, you didn't hear the 19 discussions between Indy and Bad Homburg, did you? 20 A You have given me the 21 opportunity to read this document, and anyone who 22 is familiar with the drug experience network at 23 Lilly, and I am, knows that there is confusion on 24 the part of our German colleagues with regard to 332 1 the use of the terms, the classification terms 2 suicide attempt and overdose. 3 Q What have you done about 4 it, or what did you do about it to clear up that 5 confusion and help those people in Germany? 6 A I would suggest that you 7 talk to Doctor Thompson or Doctor Zerbe, who were 8 involved in dealing directly with fluoxetine at 9 that time. 10 Q Did you do anything about 11 it, Doctor? 12 A Did I personally do 13 anything? 14 Q Yes. 15 A No. 16 Q Do you recall this issue 17 coming up? 18 A Yes. 19 Q When it came up? 20 A Only from what you've 21 shown me, but, yes, I recall the issue having come 22 up. 23 Q Do you recall getting any 24 instructions that you do something about this, 333 1 since you were the vice president of international 2 medical at the time? 3 A No. 4 Q Did you voice any opinion 5 to Doctor Weber concerning this? 6 A I don't recall. 7 Q Would Doctor Weber 8 technically be an individual that was required to 9 report to you on medical matters? 10 A You would have to define 11 what you mean technically. 12 Q Or untechnically, in any 13 way. 14 A No, he did not report to 15 me; he, in fact, reported to Mr. Bouchy. 16 Q Did Mr. Bouchy report to 17 you in any way? 18 A No. 19 Q Did you have any ability 20 to give directions or instructions to either one 21 of these individuals in Germany? 22 A I had the ability to 23 interact frequently with Doctor Weber and make 24 suggestions to him, but his direct reporting line 334 1 was not through me. 2 Q Did you interact with 3 Doctor Weber, or make any suggestions to Doctor 4 Weber concerning this issue? 5 A I don't recall any. 6 Q Were you given 7 instructions to do so? 8 A I don't recall. 9 Q Let me help you. 10 (WEINSTEIN EXHIBIT NO. 20 MARKED FOR 11 IDENTIFICATION.) 12 A I'm having difficultly 13 reading this. Is there something on which the 14 words are a little more apparent? 15 Q Well, even though I have 16 this yellow marked, mine is better, and let me, in 17 all fairness to you, give you my copy. 18 A Thank you. Okay. 19 Q Exhibit 20 is a document 20 authored the next day, is it not? 21 A Yes. 22 Q By Leigh Thompson? 23 A Yes. 24 Q And Leigh Thompson was an 335 1 individual who could give you instructions 2 concerning particular matters, could he not? 3 A Yes. 4 Q Leigh Thompson's first 5 remark about this is, "This is such a good and 6 important point, I am hereby asking that Bob Zerbe 7 and Allan Weinstein organize an appropriate group 8 to discuss it," doesn't he? 9 A Yes. 10 Q Do you disagree with 11 Doctor Thompson that the issue raised by Doctor 12 Bouchy is a good and important point? 13 A I disagree. 14 Q Did you express that 15 disagreement to Doctor Leigh Thompson? 16 A I don't recall. 17 Q Did you express that 18 disagreement to Bob Zerbe? 19 A I don't recall. 20 Q Did you organize a, 21 quote, appropriate group to discuss this issue? 22 A No. 23 Q Did Bob Zerbe organize an 24 appropriate group to discuss this issue? 336 1 A He may have, I don't 2 know. 3 Q Why didn't you organize 4 an appropriate group to discuss this issue? 5 A Issues related to Prozac 6 fell in the category of the responsibility that 7 Bob Zerbe had. If a group were, in fact, 8 organized, he would have been the one responsible 9 for organizing it. 10 Q Well, he says, "I am 11 hereby asking that Bob Zerbe and Allan Weinstein 12 organize an appropriate group to discuss it." 13 A Uh-huh, correct. 14 Q Did you send Doctor 15 Thompson a memo saying this is Prozac and I'm not 16 going to do this, that's Bob Zerbe's 17 responsibility? 18 A No, I didn't send him a 19 memo. 20 Q Did you discuss this with 21 Leigh Thompson? 22 A I don't recall. 23 Q Are you in the habit of 24 following instructions or requests made of you by 337 1 Doctor Leigh Thompson? 2 A On occasion. 3 Q Do you know of any other 4 instances where he made requests or gave 5 instructions to you that you didn't accommodate 6 him on? 7 A Many. 8 Q Give me the latest that 9 comes to mind, in connection with Prozac. 10 A Oh, I can't remember any 11 specific ones with regard to Prozac. 12 Q Did you and Doctor 13 Thompson disagree on occasion? 14 A Yes. 15 Q Frequently? 16 A On occasion. 17 Q Concerning Prozac? 18 A I don't think 19 specifically with regards to Prozac, but Doctor 20 Thompson and my views did not always coincide. 21 Q In what respect? 22 A We had different views of 23 a variety of things, from clinical research to the 24 practice of medicine. 338 1 Q In what ways did your 2 views differ on clinical research? 3 A They were different. 4 Q In what ways were they 5 different? 6 A I really can't define 7 differences other than to say that approach to the 8 design of clinical trials on occasion would be 9 different, approach to certain measurements 10 following patients might be different, the kinds 11 of differences that one would expect any two 12 academic physicians to have over scientific 13 issues. 14 Q Do you remember any 15 differences that arose between you and he on the 16 conduct of clinical trials in connection with 17 Prozac? 18 A No, but I don't remember 19 having any discussions with him on the conduct of 20 clinical trials regarding Prozac. 21 Q What differences did you 22 and Doctor Thompson have concerning the practice 23 of medicine? 24 A That probably was an 339 1 overstatement, but we looked at medicine 2 differently because we came from different 3 backgrounds. He is an intensive care unit 4 physician, an intensivist, I am an infectious 5 disease physician, so our approach to patients and 6 to taking care of patients is different. This is 7 not uncommon among academic physicians. 8 Q On the corporate 9 structure, did Doctor Leigh Thompson have the 10 authority to ask you to do a particular task? 11 A I don't recall at this 12 time who I directly reported to, but he may well 13 have had the authority to ask me to do a 14 particular task. 15 Q Does he now? 16 A No. 17 Q Well, in any event, you 18 didn't do what he requested you to do, did you? 19 A That's correct. 20 Q In response to this, what 21 he considered, good and important point, correct? 22 A Correct. 23 Q Also on the bottom of the 24 page, it says, "Bob - Allan: Could you please get 340 1 me a copy of the specific 1639's in question: 2 Could you identify which physician is making the 3 change in the classification term (these are all 4 done by MDs though they may be suggested by the 5 DEU), and let me know the rationale and the rules 6 we are using for such classifications. Then let's 7 have an appropriate group go over our system once 8 again," correct? 9 A Correct. 10 Q Did you do that? 11 A No. 12 Q He also says, "Claude and 13 Hans -- we always appreciate your thoughtful 14 questioning of the system. I don't know if we are 15 wrong or right, but we certainly haven't 16 communicated well the rationale for what we are 17 doing -- so we'll fix that for sure," doesn't he? 18 A Correct. 19 Q Do you disagree that the 20 rationale for what was going on had not been 21 communicated well? 22 A It's very possible, based 23 on Exhibit 8 and 19, that communication could have 24 been better. 341 1 Q Well, it indicates to me, 2 Exhibit 19, that, quote, "This issue has been 3 argued back and forth for about a month between 4 Bad Homburg and Indy, therefore I am bringing it 5 to your attention and await your directions," 6 correct? 7 A Correct. 8 Q Did you talk with Bob 9 Zerbe concerning this issue? 10 A I don't recall. 11 Q Why? 12 A Pardon me? 13 Q Why don't you recall 14 this? 15 A I don't recall specific 16 conversations I had three and a half years ago. 17 Q Well, do you recall 18 generally discussing this with Bob Zerbe? 19 A No. I would presume, 20 again based on the fact that Doctor Zerbe was 21 responsible for issues related to Prozac, that he 22 would have taken the lead in following through on 23 Doctor Thompson's requests. 24 Q But that's your 342 1 presumption? 2 A Correct. 3 Q Do you recall whether or 4 not Doctor Thompson ever followed up with you 5 concerning his request? 6 A I don't recall. 7 Q This request is coming in 8 from Germany, right? 9 A Exhibit 19 is coming from 10 Germany, yes. 11 Q And this has to do with 12 an international situation, does it not? 13 A Correct. 14 Q Which in some respects 15 falls within your jurisdiction, doesn't it? 16 A Correct. 17 Q Apparently Doctor Leigh 18 Thompson felt that it fell within your areas of 19 responsibility since he directed you to do two 20 things, doesn't he? 21 A Correct. 22 Q But you don't recall 23 doing them? 24 A No. 343 1 Q In fact, you say it's 2 your testimony you didn't do it? 3 A That's correct. 4 Q Turn with me to the 5 second page of Exhibit 20, which is apparently a 6 response from Bouchy back to you fellows there in 7 Indianapolis, correct? 8 A No. Mr. Bouchy's message 9 is written prior to Doctor Thompson's message, so 10 it cannot be a response. 11 Q Well, there must have 12 been some earlier response, correct? 13 A There must have been, 14 but -- 15 Q Because it says, "Thank 16 you very much for your prompt answer and your 17 detailed explanations. Hans and I rediscussed the 18 issue in depth," doesn't he? 19 A That's what it says. 20 Q If it's 6:47 in Germany, 21 what time will it be in Indianapolis? 22 A All electronic mail is 23 based on Indianapolis time. 24 Q All right. The computer 344 1 just automatically -- 2 A It automatically gives 3 Indianapolis time, so this message was written 4 roughly eight minutes before Doctor Thompson's 5 message, and therefore cannot be a response, there 6 must have been other communication of which I'm 7 not aware that this is responding to. 8 Q We haven't seen any 9 communication of that. Do you recall, generally, 10 what might have been transmitted in the interim? 11 A No, you would have to ask 12 Doctor Thompson. 13 Q In that document, about 14 two-thirds of the way down, Mr. Bouchy says, 15 "Finally, on a very simple and non-scientific 16 basis, I personally wonder whether we are really 17 helping the creditability of an excellent ADE 18 system by calling overdose what a physician 19 reports as suicidal attempt and by calling 20 depression what a physician is reporting as 21 suicide ideation," correct? 22 A Correct. 23 Q Do you have any 24 criticism, Doctor, of calling overdose what a 345 1 physician reports as suicide attempt? 2 A I have no criticism of 3 using FDA acceptable event term classifications. 4 Q That's not what I asked 5 you. Do you have any criticism of calling 6 overdose what a physician reports as suicide 7 attempt? 8 A No. 9 Q Do you have any criticism 10 of a physician reporting suicide ideation and 11 calling it depression? 12 A No. 13 Q Why not? 14 A Because those are the 15 terms that have been agreed to by the FDA and have 16 been mandated by the FDA, and in all cases the 17 individual physician's narrative, which uses his 18 or her words, is submitted to the government. 19 Q But when the government 20 reports these adverse events, they report it under 21 the event term, don't they? 22 A That's correct. 23 Q And that's the problem, 24 isn't it, because what's going to be reported by 346 1 the government as depression was actually suicidal 2 ideation, correct? 3 A You would have to ask the 4 FDA how they make these determinations. In fact, 5 the narrative summary is submitted to the FDA in 6 all cases. 7 Q Beg your pardon? 8 A The narrative summary is 9 submitted to the FDA in all cases. 10 Q But I'm talking about 11 what's reported by the FDA in these tabular 12 compilations. Isn't that the purpose of having 13 classification systems? 14 A Correct. 15 Q And what's going to 16 happen, isn't it, is that you're going to have the 17 FDA reporting a certain number of events that are 18 reported as depression, when in fact what was 19 occurring, as reported by the physician, was 20 suicidal ideation, isn't it? 21 A In the event 22 classification report, it would be reported in the 23 way you've characterized it, yes. 24 Q And you have a situation 347 1 where somebody attempted suicide, in fact, and 2 when you look at the event term reporting, it's 3 going to be overdose, right? 4 A If the person was 5 receiving a medication, correct. 6 Q And if all a person was 7 looking at was the compilation of FDA event terms 8 with respect to adverse events on a particular 9 drug, they're not going to get the full story 10 about what's really happening with what the 11 physician is reporting about what was occurring on 12 the drug? 13 A If all a person looked at 14 were the event classification terms, you're 15 correct. 16 Q And the FDA doesn't 17 publish the entire text of the entire 1639's, do 18 they? 19 A No. 20 Q They report in event term 21 classification what Lilly reports to them 22 according to the event term, isn't it, don't they? 23 A Correct. 24 Q And that's the criticism 348 1 that Claude Bouchy and Hans Weber had, was that 2 they were reporting an event term that really 3 wasn't what was happening with the drug, isn't it? 4 A The classification term 5 was the one that these statements mapped to, 6 that's correct. 7 Q And that's what the 8 criticism was? 9 A That's correct. 10 Q Is that it was leading to 11 confusion? 12 A Confusion on the parts of 13 Mr. Bouchy and Doctor Weber. 14 Q Well, Mr. Bouchy, in fact 15 said, "I do not think I could explain to the BGA, 16 to a judge, to a reporter, or even to my family 17 why we would do this, especially on the sensitive 18 issue of suicide and suicide ideation," correct? 19 A Correct. 20 Q Do you disagree with him? 21 A Yes. 22 Q You don't have any 23 problems with the Food and Drug Administration 24 reporting as an event term depression, when 349 1 actually what the physician actually reported was 2 suicidal ideation? 3 A No, I have no problems 4 with that. 5 Q And you don't have any 6 problem with the Food and Drug Administration 7 reporting to the public overdose, when in fact 8 what occurred was the patient attempted suicide? 9 A No, I have no problems 10 with that. 11 Q You don't think that 12 misleads a person looking at a tabulation of 13 adverse events in connection with Prozac 14 concerning what was going on with the drug? 15 A No. 16 Q You view suicidal 17 ideations and depression as the same thing, is 18 that what you're telling us? 19 A No. 20 Q All right. Don't you 21 think there should be some distinction made in 22 classifying event terms that accurately reflect 23 what the adverse event is with the drug? 24 A I am comfortable using 350 1 the worldwide accepted classification terms. 2 Q So you don't think there 3 should be any -- 4 A I don't see a need to 5 change the terms. 6 Q What requirement is there 7 by the FDA that you use Co-Start event term 8 selection? 9 A I'm not familiar with the 10 details. That is their preferred use of 11 classification, and I believe Lilly has decided 12 that Co-Start would be the model for how we 13 report. 14 Q But it's not accurate to 15 say that the FDA requires it, is it? 16 A No, it's not -- does not 17 have a regulation that specifically states that. 18 Q The regulation states 19 that the adverse event be accurately reported by 20 the company, doesn't it? 21 A And it is. 22 Q No, I didn't ask you 23 that; I said the FDA requirement is, is that the 24 adverse event be accurately reported by the 351 1 company, isn't it? 2 A Correct. 3 Q So there is no 4 requirement by the FDA that when a person reports 5 suicidal ideations that it be reported to the FDA 6 under event term classification as depression, is 7 there? 8 A It's not formally 9 required, no. 10 Q And there is no 11 requirement by the FDA that when an individual 12 attempts suicide, that it be reported as overdose 13 as an event term classification, is there? 14 A There is no formal 15 requirement. 16 (WEINSTEIN EXHIBIT NO. 21 MARKED FOR 17 IDENTIFICATION.) 18 MR. FREEMAN: Do you have 19 any better copy of that, Paul? Half of this is 20 off the page. 21 MR. SMITH: That's my 22 copy. 23 MS. ZETTLER: That's the 24 way it was produced to us. 352 1 MR. FREEMAN: Yours is 2 the same way? 3 MR. SMITH: Maybe Larry 4 could look into -- 5 MR. MYERS: I'm not 6 looking into that, I have done all my looking for 7 today. 8 Q (BY MR. SMITH) Doctor, 9 Exhibit 21 is a message concerning suicide and 10 reporting suicide, is it not? 11 A Yes. 12 Q And it had to do also 13 with something in connection with the BGA, right? 14 A Yes. 15 Q Because there is the 16 notation, "Message dated December 7, 1990," 17 quote, "'Re: BGA - Suicide - Our response,'" end 18 quote, then C. Bouchy is beside it, isn't it? 19 A Correct. 20 Q And it looks like this 21 particular exhibit is directed to Hans, correct? 22 A Correct. 23 Q You're not copied on 24 this, but you've indicated that you feel you're 353 1 very familiar with the rules of the DEN in 2 reporting event classifications, correct? 3 A Correct. 4 Q All right. The document 5 states, "Can you give us some unique identifier 6 for the patient that Claude Bouchy referenced in 7 his message? He described a patient that you have 8 that committed suicide, had no concomitant meds 9 and the reporting physician states suicide was 10 caused by a surge of serotonin. According to 11 Claude the Indy monitor judged the report to be 12 not related. If you have the DEN number that 13 would be great," correct? 14 A Correct. 15 Q If a physician reported 16 to Indianapolis that a patient committed suicide, 17 isn't there an event term for suicide? 18 A Yes. 19 Q By Co-Start 20 classification? 21 A Yes. 22 Q And isn't Lilly supposed 23 to report that as suicide under event term 24 suicide? 354 1 A Yes. 2 Q If the reporting 3 physician states that the suicide was caused by a 4 surge of serotonin, should that be noted on the 5 data that's reflected on the 1639? 6 A It should be. 7 Q The document states, 8 "According to Claude the Indy monitor judged the 9 report to be not related." That would be 10 inaccurate, would it not? 11 A I have no way of 12 interpreting statements attributed to Claude 13 Bouchy and attributed to a nonidentified Indy 14 monitor; I can't make a judgment. 15 Q See, I don't know either, 16 but this is a document that was provided to us by 17 Eli Lilly and Company. 18 A I accept that, but I 19 can't comment on what Claude Bouchy might have 20 said to some other person and what some 21 unidentified Lilly monitor must have said -- might 22 have said to some third person. I really don't 23 feel qualified to make any judgment about what 24 this means; I've not seen this message before. 355 1 Q Have you got any 2 explanation as to why a monitor in Indy would be 3 reporting this as not related? 4 A I'm not even sure that a 5 monitor in Indy did report it as nonrelated, I 6 really don't -- 7 Q Has Claude Bouchy ever 8 lied to you? 9 A This is not Claude Bouchy 10 speaking, this is someone quoting Claude Bouchy. 11 No, Claude Bouchy has never lied to me. 12 Q Do you know of any 13 instances where Claude Bouchy has been untruthful? 14 A No. 15 Q Do you know any instances 16 in which Hans Weber has ever lied to you? 17 A No. 18 Q Do you know of any 19 instances where Hans Weber has been untruthful? 20 A No. 21 Q At the time, were Claude 22 Bouchy and Hans Weber valued employees of Eli 23 Lilly and Company? 24 A Yes. 356 1 Q And isn't Doctor Hans 2 Weber still a valued employee of Eli Lilly and 3 Company? 4 A Correct. 5 Q Isn't he still head of 6 the German association of Lilly in Germany? 7 A Germany medical group, 8 yes. 9 Q Isn't that an area of 10 some degree of responsibility? 11 A Correct. 12 Q Claude Bouchy is no 13 longer with Lilly, but when he left Lilly, what 14 was his position? 15 A He was the general 16 manager of Lilly Germany. 17 Q The general manager of 18 the entire Lilly German operation? 19 A Correct. 20 Q How many employees were 21 there at that time, at the time he left? 22 A I think a few hundred, I 23 don't know the specific number. 24 Q So Claude Bouchy had the 357 1 responsibility of a, quote, few hundred people, 2 did he not? 3 A Correct. 4 Q So apparently it sounds 5 to me like at the time somebody respected these 6 people's ability and judgment, correct? 7 A Correct. 8 Q So you're not implying to 9 me, are you, that you think that Claude Bouchy, in 10 his message, is describing anything inaccurately, 11 are you? 12 A I didn't say that, no. 13 Q You just wonder whether 14 or not the person that talked to Claude is 15 describing it inaccurately? 16 A I don't know whether he 17 is describing it accurately or not. 18 Q On the top of the page, 19 it says from Richard D. Huddleston, does it not? 20 A Correct. 21 Q Who is Richard D. 22 Huddleston? 23 A I believe he is a person 24 who worked in the drug experience unit at that 358 1 time. 2 Q Do you know him? 3 A I know who he is. 4 Q Do you have any reason 5 that he would be untruthful? 6 A No. 7 Q Do you have any reason to 8 believe that he would inaccurately report what 9 Claude Bouchy said? 10 A No. 11 Q Have you seen any 12 criticism of Richard D. Huddleston as an employee 13 of Eli Lilly and Company, at any time? 14 A No. 15 Q Under any circumstances? 16 A No. 17 Q Why did Claude Bouchy 18 leave Eli Lilly and Company? 19 A I don't know. I was not 20 involved at the time, and why he left, I don't 21 know the reason. I know he had another -- he's 22 gone on to some other kind of employment. 23 Q Is he still in the 24 pharmaceutical industry? 359 1 A I don't know that. 2 Q What is the significance 3 in reporting requirements concerning adverse 4 events of a product of whether or not the adverse 5 event is expected or unexpected? 6 A Depending on the country, 7 that determines the speed with which reporting 8 should be carried out. 9 Q All right. But it 10 doesn't have anything to do with whether or not 11 the events should be reported, does it? 12 A No. 13 Q It's whether you report 14 it, what, in fifteen days, within a day or -- 15 A It depends on the 16 country, yes, but unexpected events, serious, 17 particularly serious unexpected events are 18 required by various regulations to be reported 19 fairly quickly. Expected events have to be 20 reported also, but not with those shorter time 21 frames. 22 (WEINSTEIN EXHIBIT NO. 22 MARKED FOR 23 IDENTIFICATION.) 24 Q Exhibit 22 is a document, 360 1 also in December of 1990 from Doctor Hans Weber 2 directed to Gilad Gordon, correct? 3 A Correct. 4 Q And you were copied in on 5 this document, correct? 6 A Correct. 7 Q Who is Gilad Gordon? 8 A He was formerly one of 9 the research physicians at Lilly. 10 Q Where is he now? 11 A The last I knew, he 12 worked for a company called Synergem in Colorado. 13 Q When did he leave Lilly? 14 A It probably was 1992. 15 Q The document says, 16 "Comments: Gilad, referred to you as the 17 expert," correct? 18 A Correct. 19 Q Who is Rick? 20 A I assume that's 21 Mr. Huddleston that was referred to in the last 22 message. 23 Q It goes on to say, "The 24 highlighted event compilation arrived 2 days 361 1 ago,. Thus, this is clarified although for the 2 BGA response it may need to be up-dated. 3 Currently we try to make ourself familiar with the 4 data. Also I understand that an event which is 5 serious, unexpected and possibly causally related 6 goes to CIOMS. A suicide certainly is serious and 7 as I learned unexpected. Therefore, it seems to 8 depend on assessment of relationship whether it 9 goes to CIOMS. Right?" 10 He then goes on to say, 11 "In Q2'90 we had 46 suicides, 4 went to CIOMS. 12 In Q3'90, we had 122 total, 19 of them CIOMS. My 13 question exactly is how we distinguish between 14 reports judged possibly causally related or 15 unrelated," correct? 16 A Correct. 17 Q Can you give me some 18 clarification as to what he's talking about there? 19 A I can only read what 20 you've read, and I assume, as I'm sure you do, 21 that the question is that Doctor Weber is 22 questioning Gilad Gordon about what criteria are 23 used to determine the relation or the relatedness 24 between these events and the compound being given, 362 1 and I don't see any response from Doctor Gordon, 2 so I don't think I can add anything to what you've 3 said. 4 Q Well, he states here that 5 in the second quarter of 1990 there were forty-six 6 suicides and only four were reported to CIOMS, 7 does he not? 8 A Correct. 9 Q Does that mean that if 10 you looked at the CIOMS data, you would only see 11 four reports of suicide of individuals using 12 Prozac for that quarter? 13 A That apparently is 14 correct, yes. 15 Q And does that mean in 16 quarter three, even though there were a hundred 17 and twenty-two individuals taking Prozac that 18 committed suicide, if you looked at the CIOMS 19 data, it would only show that there were nineteen 20 who had committed suicide? 21 A That's apparently 22 correct. 23 Q Does that mean then that 24 there are individuals who committed suicide while 363 1 on Prozac that were not being reported to this 2 regulatory body? 3 A CIOMS is not a regulatory 4 body. 5 Q What is it? 6 A CIOMS is a group that is 7 put together to try to standardize the forms that 8 are used for reporting adverse events around the 9 world. It has representatives of regulatory 10 bodies; it also have a number of representatives 11 of industry. This is not a governmental agency. 12 Q But there are 13 governmental agencies within the group, are there 14 not? 15 A No, there are no agencies 16 within the group. There are representatives from 17 governmental agencies who are members of CIOMS; 18 however, there are also members of industry who 19 are representatives of CIOMS. 20 Q Whether they're 21 governmental groups or members of governmental 22 groups, they reviewed the CIOMS data, did they 23 not? 24 A CIOMS data is 364 1 supplementary to the individual reports that are 2 sent to every country. 3 Q I understand that, but 4 CIOMS reports their data, do they not? 5 A They report their data. 6 Q CIOMS collects data? 7 A CIOMS collects what data 8 is available. Since all companies do not 9 participate in the CIOMS program, they collect 10 apparently incomplete data. 11 Q Are you saying then that 12 the CIOMS data is worthless? 13 A No, I'm saying that CIOMS 14 is a venture that has started within the last few 15 years and is gradually building itself to become a 16 very effective organization, but certainly by 17 December 1990 it had not gotten there yet, and in 18 fact many of the major pharmaceutical companies of 19 the world did not participate in this program, as 20 opposed to Lilly, which did. 21 Q Lilly obviously had some 22 faith in it or they wouldn't be involved with it. 23 A Correct. 24 Q And Lilly was reporting 365 1 some of its data to CIOMS, wasn't it? 2 A It was reporting data 3 according to the criteria that the CIOMS working 4 group had set up, that's correct. 5 Q My question was, Lilly 6 was reporting some of its data to CIOMS, wasn't 7 it? 8 A Lilly was reporting all 9 of its data to CIOMS. 10 Q Well, I don't know about 11 that. What Hans Weber is saying in quarter two of 12 1990, we had forty-six suicides and four went to 13 CIOMS. 14 A That's correct. 15 Q So it doesn't look like 16 it's reporting all of its data in quarter two of 17 1990. 18 A Doctor Weber says that 19 there are criteria that are utilized for CIOMS 20 that involve serious, unexpected and possibly 21 causally related. He would like Doctor Gordon, I 22 believe, to help him understand how one 23 distinguishes between possibly causally related 24 and unrelated. 366 1 Q Do you want to answer my 2 question, Doctor? 3 A What's your question? 4 MR. SMITH: Read it back 5 for him. 6 REPORTER: (READING) So 7 it doesn't look like it's reporting all of its 8 data in quarter two of 1990. 9 MR. FREEMAN: He has 10 answered the question by saying they reported it 11 according to the criteria, that's what he just 12 said, and that's responsive to the question. 13 MR. SMITH: He hasn't 14 answered the question. 15 MR. FREEMAN: He's 16 answered the question, go on to something else. 17 Q (BY MR. SMITH) Doctor 18 Weinstein, if there were forty-six suicides in the 19 second quarter of 1990 and you only reported four 20 of those to CIOMS, you're not reporting all the 21 suicides to CIOMS, are you? 22 A No. 23 Q Okay. And if there were 24 a hundred and twenty-two suicides by individuals 367 1 on Prozac in the third quarter of 1990, and you're 2 only reporting nineteen of those, you're not 3 reporting all of your data to CIOMS, are you? 4 A No. 5 Q So CIOMS -- 6 MR. FREEMAN: Wait a 7 minute, let him explain his answer, you 8 interrupted him. 9 MS. ZETTLER: He wasn't 10 about to, Joe. 11 MR. FREEMAN: He has a 12 right to explain his answer, let him explain his 13 answer. 14 MS. ZETTLER: If you 15 don't like the question, you can ask him to 16 clarify it at the end when you have an opportunity 17 to ask him questions. 18 MR. FREEMAN: Go ahead 19 and explain the answer. 20 Q (BY MR. SMITH) Do you 21 need an explanation to answer the question that 22 was posed to you? 23 A I would like to make an 24 explanation that we reported according to the 368 1 criteria that CIOMS requested, and that all 2 requests and requirements under the evolving CIOMS 3 system were met. 4 Q That's your opinion? 5 A No, that is not my 6 opinion, that is consistent with the rules that 7 CIOMS had promulgated. 8 Q Where are the CIOMS rules 9 and regulations concerning this reporting? 10 A There are a number of 11 reports that I believe you could get through the 12 World Health Organization, of which CIOMS is an 13 arm, that goes through the recommendations from 14 the so-called CIOMS working group, and those have 15 been published on a regular basis. 16 Q Are you on the CIOMS 17 working group? 18 A No. 19 Q Are you a member of the 20 CIOMS body independently? 21 A I am not personally a 22 member, no. 23 Q Are you an advisor to 24 CIOMS? 369 1 A No. 2 Q Have you ever 3 participated in any CIOMS conventions where rule 4 making was a part of its criteria? 5 A No. 6 Q Have you ever been to a 7 CIOMS meeting? 8 A No. 9 Q How are you so familiar 10 with those rules that you can say so dogmatically 11 that at that time Lilly was accurately reporting 12 data to CIOMS according to the regulations? 13 A Because Lilly has had a 14 member on the CIOMS working group and I have 15 discussed the results with him. 16 Q And he told you that they 17 were accurately reporting the data, according to 18 their regulations? 19 A Correct. 20 Q Who was that? 21 A Doctor Max Talbott. 22 Q Oh, we talked to him. He 23 neglected to mention to us the rules and 24 regulations with respect to CIOMS reporting? 370 1 MR. FREEMAN: Because you 2 didn't ask him. 3 MR. SMITH: Let me take 4 that back, he neglected to volunteer, like you 5 have, the rules and regulations concerning CIOMS 6 reporting. 7 MS. ZETTLER: And Joe 8 neglected to volunteer it, too. 9 (LUNCH BREAK TAKEN.) 10 Q (BY MR. SMITH) Doctor, 11 let's go back to Exhibit 22, if we can. 12 MR. FREEMAN: 20 what? 13 MR. SMITH: 22, the CIOMS 14 exhibit. 15 Q (BY MR. SMITH) The 16 document, about the middle of the first paragraph, 17 Doctor Weber states, "Also, I understand that an 18 event which is serious, unexpected, and possibly 19 causally related goes to CIOMS," is that right? 20 A Correct. 21 Q Is that correct? 22 A Correct. 23 Q That in order to go to 24 CIOMS, the event must be serious, unexpected, and 371 1 possibly causally related? 2 A That's my understanding. 3 Q That was the regulation 4 or the rules then? 5 A It's not a regulation, 6 it's the practice, yes. 7 Q So, if in the first 8 quarter, as stated here, of 1990, four events 9 concerning suicide and suicidal attempts went to 10 CIOMS, someone at Lilly would have had to judge 11 that event as serious, unexpected, and possibly 12 causally related to the drug, correct? 13 A Correct. 14 Q And if in the third 15 quarter of 1990 nineteen attempted suicides or 16 suicides of individuals on Prozac went to CIOMS, 17 it would be because somebody at Lilly had made a 18 determination that the suicide or suicide attempt 19 was serious, unexpected, and possibly causally 20 related to use of Prozac, correct? 21 A Correct. 22 Q Has Lilly continued to 23 report suicide attempts and suicides to CIOMS? 24 A I believe so. 372 1 Q And did you say earlier 2 that that report would be contained in some World 3 Health Organization manual? 4 A No, I said that these 5 were reported to CIOMS, which is a, if you will, 6 subsidiary of the World Health Organization, I'm 7 not familiar with what manuals they publish. 8 Q I was just wondering, if 9 I wanted to get a CIOMS printout for suicides of 10 people, or attempted suicides for people on Prozac 11 that were reported by Lilly as serious, 12 unexpected, and possibly causally related for, 13 say, 1991, how would I do that? 14 A I believe there is an 15 address that is available in Geneva, I believe, 16 where the offices of CIOMS are, and they could be 17 contacted. 18 (WEINSTEIN EXHIBIT NO. 23 MARKED FOR 19 IDENTIFICATION.) 20 Q Exhibit 23 appears to be 21 a series of E-mails in house at Lilly 22 Indianapolis, and maybe from outside the country, 23 does it not? 24 A Yes. 373 1 Q It would appear that 2 these communications span about a week, from 3 February 1, 1990 until February 7, 1990, correct? 4 A Correct. 5 Q I'm going to have to ask 6 for your assistance in deciphering some of this by 7 virtue of some terminology and by virtue of the 8 way this is set up. 9 A Okay. 10 Q It looks to me like the 11 first communication, in order here at least, is 12 February 1, 1990, and that's contained on the last 13 page, Page 4, of this document, is that right? 14 A Correct. 15 Q It says to Michael Doyle, 16 "Reply to: Anonymised single patient prints from 17 CSM," is that right? 18 A Correct. 19 Q What is anonymised? 20 A Anonymised means that 21 there's no name identifying the patient. 22 Q Is that like anonymous? 23 A It's like anonymous, it's 24 just the British terminology. 374 1 Q Okay, I thought it might 2 be medical terminology. "Anonymised single 3 patient prints from CSM," does it say? 4 A Yes. 5 Q What is CSM? 6 A Committee of Safeties in 7 Medicine. 8 Q Where is the Committee of 9 Safety in Medicine located? 10 A In the UK. 11 Q Is that the English 12 equivalent to the United States Food and Drug 13 Administration? 14 A In essence, yes. 15 Q In essence, is there any 16 real difference? 17 A Yes, there is in the 18 sense that this is managed by a person who is not 19 a government employee, but is largely populated by 20 people who are -- or largely staffed by people who 21 are not government employees, but it serves as the 22 agency linked with the government that approves 23 and reviews information on medicines. 24 Q Does the CSM act as a 375 1 commission like Commission A with the BGA? 2 A It's more like that than 3 you would find in the FDA. The end result is the 4 same, it's just a different structure. 5 Q The document is from Max 6 Talbott? 7 A Correct. 8 Q And he says, "Michael, I 9 am truly sympathetic on these but feel that we 10 cannot afford not to enter them in DEN. Insofar 11 as not being able to follow up the request from 12 the DEU are routine and are generally sent on all 13 reports at one time or another. As far as entry 14 time is concerned, if getting these into the 15 system in the required time is a resource issue, 16 let me know and I can do what I can to get you 17 some help. FDA is starting to 'ratchet up' on the 18 scrutiny of ADR report timing so we need to have 19 as spotless a record as possible. I fully 20 appreciate your plight so please let me know how I 21 can help out," correct? 22 A Correct. 23 Q Who is Michael Doyle? 24 A He works for Lilly in the 376 1 UK. 2 Q It appears to me that 3 there is some question about the amount of time 4 it's taking to enter the appropriate data into the 5 Drug Experience Network with respect to adverse 6 events? 7 A It appears that there is 8 some issue related to time in the UK, that's 9 correct. 10 Q And it has to do with 11 adverse event reporting, does it not? 12 A It appears that it's the 13 amount of time necessary to enter reports, adverse 14 events reports. 15 Q And DEN, D-E-N, stands 16 for Drug Experience Network, which is the computer 17 database at Lilly, of Lilly, where Lilly stores 18 their record of adverse experiences with drugs? 19 A Correct. 20 Q Including Prozac? 21 A Correct. 22 Q DEU is that group within 23 Lilly that is responsible for collecting the data 24 that's put in the DEN system, is that right? 377 1 A Correct. 2 Q Go with me to the top of 3 the page. It appears to be a transmission later 4 to Patrick Keohane, correct? 5 A Correct. 6 Q Who is Patrick Keohane? 7 A At the time he was the 8 medical director, Lilly medical director in the 9 UK. 10 Q Where is he now? 11 A In Indianapolis. 12 Q As a Lilly employee? 13 A Yes. 14 Q In what capacity? 15 A He is the director of the 16 area of concentration in endocrinology. 17 Q Is he an endocrinologist? 18 A No. 19 Q Why has he got that job 20 then? 21 A Because he basically has 22 an administrative function; he has 23 endocrinologists reporting to him who do the 24 implementation and design of studies. 378 1 Q The document says, 2 "Comments: Patrick," correct? 3 A Correct. 4 Q It's signed by Mike, and 5 I assume that's Michael Doyle; is that a 6 reasonable assumption? 7 A That's correct, based on 8 the listing on the bottom which tells who sent the 9 message. 10 Q Who would have put 11 "Comments: Patrick," Michael Doyle? 12 A Well, comments appears on 13 the screen all the time. Every screen that comes 14 up that is a response you will have comments. In 15 other words, when electronic mail comes and a 16 message comes in, and you push on the keys reply, 17 the first thing that'll come up is comments, so 18 that's just part of the computer system. Patrick 19 is -- presumably that's Michael addressing 20 Patrick. 21 Q "No let up. It is quite 22 impossible for 70 aspp's to be put into ears 23 within 48h of receipt unless we do it ahead of 24 everything else. I have always felt that this is 379 1 relatively low priority." "How can we take Max up 2 on his offer of support, regards, Mike," correct? 3 A Correct. 4 Q What is an ASPP? 5 A It refers to what you 6 described earlier, anonymised single patient 7 printout. 8 Q Well, would you have an 9 anonymised single patient printout when you didn't 10 know the name of the individual who was 11 experiencing the adverse experience with the drug? 12 A In the UK, the system is 13 somewhat different than it is in other countries, 14 and in addition to event reports being reported to 15 the company, they're also reported to the CSM, to 16 the regulatory agency. On a periodic basis, and I 17 believe it is quarterly, the CSM sends to the 18 company all of the reports that it has received on 19 that particular company's products. Those are 20 anonymised so that there is no identification of 21 the people involved, and this is, I believe, 22 indicating that at some time before February 1, 23 1990, seventy anonymised single patient printouts 24 were sent by the CSM to Lilly in the UK. 380 1 Q And I assume, based on 2 the other pages of this document, that they had to 3 do with Prozac and adverse experiences in 4 connection with Prozac? 5 A I agree they apparently 6 had to do with adverse experiences related to 7 Prozac. 8 Q What is EARS, E-A-R-S? 9 A I'm not entirely sure. I 10 believe that is an acronym for a computer system 11 in which the data would have been entered in the 12 UK, into the corporate database, but Michael Doyle 13 or Patrick Keohane would have to clarify that. I 14 believe that's what it's referring to. 15 Q All right, so Michael 16 Doyle is saying we've got a large amount of 17 adverse experiences that we have received that we 18 have got to get in our computer, in fact we 19 received seventy within forty-eight hours, is that 20 right? 21 A No, it doesn't say 22 seventy within forty-eight hours. 23 Q Okay, they received -- 24 A They received seventy. 381 1 Q But was there some 2 requirement that they be entered into the Lilly 3 EARS computer within forty-eight hours? 4 A No, that's the corporate 5 requirement of all employees for adverse event 6 reporting, that when an employee is made aware of 7 an event, he or she must report it within 8 forty-eight hours, and I think Mr. Doyle is saying 9 I received these seventy, therefore I am under a 10 corporate obligation to report these, to put these 11 into the system within forty-eight hours. 12 Q And then he's going on to 13 say that he's always felt this is a low priority, 14 correct? 15 A That's what he says. 16 Q Obviously there had been 17 some other communication between Mr. Talbott and 18 Mr. Doyle in connection with this problem, 19 correct? 20 A Yes, it would appear to 21 be correct. 22 Q Because they're having 23 this discussion concerning this? 24 A Correct. 382 1 Q And it appears to be that 2 there's more information concerning it that we 3 don't have in front of us? 4 A Correct. 5 Q Then I guess the next 6 communication is on February 2, 1990, and is 7 contained on the bottom of Page 3, and it's from 8 Keohane? 9 A Keohane, yes. 10 Q Keohane to Max Talbott? 11 A Correct. 12 Q And he's talking about 13 the work load continuing to increase because 14 Prozac sales were increasing, correct? 15 A Correct. 16 Q And they were receiving 17 and processing an increasing number of I-F-D comma 18 S. What is that? 19 A That's the abbreviation 20 for International Full Disclosure, which is the 21 corporate package insert. 22 Q Corporate package insert? 23 A Yes. 24 Q I don't understand. 383 1 A When drugs are developed, 2 all of the data that is available is designed in 3 the form of a package insert; that package insert 4 is, in fact, identical to what is used -- will be 5 used by the US FDA, and that is sent out to the 6 various affiliates for their review to judge 7 whether the statements in that IFD, that 8 International Full Disclosure, are consistent with 9 local regulation. 10 I do not interpret this 11 to mean that these are Prozac IFD's. We 12 constantly are sending out International Full 13 Disclosures on all of our products because there 14 are changes made, and my interpretation of this is 15 that they have a significant work load and part of 16 it is related to IFD's. 17 Q Because he says, we got 18 increasing Prozac sales plus we're receiving and 19 processing IFD's? 20 A It would be my impression 21 that they are not related, that this is not in 22 reference to Prozac, but more in reference to 23 package insert change procedures that go on 24 constantly. 384 1 Q But then he goes on to 2 talk about the ASSP issue, correct? 3 A Correct. 4 Q And that is an adverse 5 event report concerning Prozac, right? 6 A It would appear to be 7 related to the statements on the earlier page. 8 Q And he says adding to the 9 load, so he currently has the equivalent of three 10 people just on safety monitoring. This is ten 11 percent of the medical division, correct? 12 A Correct. 13 Q And he says, "I plan to 14 put one more person full time into this area now. 15 Your support for maintaining a strong safety 16 monitoring group would be appreciated," right? 17 A Correct. 18 Q Then it appears what 19 happens next is that Talbott issues a memo to 20 Robert L. Zerbe on February 6, 1990, is that 21 right? 22 A Correct. 23 Q And Mr. Talbott says to 24 Doctor Zerbe, "Bob, this will supplement a note 385 1 that I just sent you on the most recent Elapsed 2 Time Report. You might want to print this off and 3 then have it at hand when you get the ETR with my 4 note. Let's chat about this when we next have a 5 moment together. Thanks, Max," right? 6 A Right. 7 Q What is an ETR? 8 A Elapsed Time Report. 9 Q What is an Elapsed Time 10 Report? 11 A I believe it's the time 12 from -- I think it can be interpreted two ways 13 actually, the time from when an event occurred to 14 when it was reported to Lilly, and the time Lilly 15 became aware of an event and it was entered into 16 the Drug Experience Network. 17 Q Okay. So you're keeping 18 records with respect to how long it takes an 19 adverse event to get to Lilly? 20 A We keep those records, 21 yes. 22 Q And then you keep a 23 record of how long it takes for Lilly to get the 24 report to the appropriate regulatory body, is that 386 1 right? 2 A Correct -- well, it's the 3 first, and I think the Elapsed Time Report really 4 refers more to when it gets into the Drug 5 Experience Network. 6 Q Okay, so when it gets in 7 the Drug Experience Network, that's recorded? 8 A Correct. 9 Q Then it has to go from 10 the Drug Experience Network to the appropriate 11 regulatory body within a specified time, depending 12 on the nature of the event, is that right? 13 A Correct. 14 Q And that also has to be 15 done timely? 16 A Correct. 17 Q So you've got several 18 time deadlines and guidelines that are being 19 mentioned here? 20 A That is correct. 21 Q Then the next thing that 22 occurs appears to be on the top of Page 3 where 23 Doctor Zerbe is speaking to or issuing a note to 24 Mr. Talbott and copying in Doctor Thompson saying, 387 1 "We must see that Prozac info is handled in an 2 absolutely foolproof manner. The UK makes me 3 really nervous. They have to get a clear message 4 that there is no higher priority than Prozac 5 because of its worldwide impact," correct? 6 A Correct. 7 Q Did you discuss this with 8 Doctor Zerbe? 9 A No, not that I'm aware. 10 I'm not even copied on any of these messages, so I 11 don't -- 12 Q That's why I asked you if 13 you discussed it with Doctor Zerbe. 14 A I don't recall discussing 15 it with Doctor Zerbe. 16 Q Were you aware of Doctor 17 Zerbe's concern then about some problem in 18 England? 19 A No. 20 Q You see there he says the 21 UK makes me really nervous? 22 A I see that. 23 Q Do you have any idea what 24 it was about the United Kingdom that was making 388 1 him nervous? 2 A No, I think you would 3 have to ask Doctor Zerbe. I don't know what this 4 is about. 5 Q He didn't have any 6 particular interest in the Charles and Diana 7 issue, did he? 8 A Well, he may have, but I 9 doubt that he was writing electronic mail messages 10 about that. 11 Q Obviously his concern was 12 in connection with Prozac, right? 13 A (WITNESS MOVES HEAD UP 14 AND DOWN.) 15 Q Because he mentions 16 Prozac? 17 A It appears that his 18 concern was about Prozac. 19 Q And he was concerned 20 about information about Prozac being handled in an 21 absolutely foolproof manner, correct? 22 A Correct. 23 Q Do you have any idea what 24 he means by that? 389 1 A No. 2 Q You can't give us any 3 help in connection with -- since you're the 4 international vice president, of what he might 5 mean by "the UK makes me really nervous"? 6 A No, I think you would 7 have to ask him. As these messages show, I wasn't 8 involved in this interchange. 9 Q Well, but you do get 10 involved, don't you, later on? 11 A Later on. 12 Q Well, within an hour and 13 twelve minutes you get involved, don't you? 14 A Well, not necessarily; 15 that's when the message was sent, I may not have 16 read it. 17 Q Within an hour and twelve 18 minutes -- 19 A The message was sent to 20 me. 21 Q -- your computer is 22 blinking at you, isn't it? 23 A The computer doesn't 24 blink, but a message was sent to me an hour and 390 1 ten minutes later. 2 Q Doctor Leigh Thompson, in 3 response to this, obviously, directs a note to you 4 at 8:56 that morning, along with Patrick Keohane, 5 Max Talbott and Bob Zerbe, does he not? 6 A I'm sorry, which message 7 are you referring to now? 8 Q The one on Page 1. It 9 goes first, doesn't it? 10 A Oh, that's -- okay, yes. 11 Q And he's specifically 12 talking about Prozac safety reports, is he not? 13 A Correct. 14 Q He says, "I wish to 15 reemphasize the message from Bob Zerbe and Max 16 Talbott in regards in terms of the resource needs 17 to stay absolutely on top of every Prozac adverse 18 event. Anything that happens in the UK can 19 threaten this drug in the US and worldwide. We 20 are now expending enormous efforts fending off 21 attacks because of (1) relationship to murder and 22 (2) inducing suicidal ideation. The appropriate 23 level of response is indicated by Dan Masica 24 himself and Charles Beasley immediately flying to 391 1 Boston to talk to authors of a paper on suicidal 2 ideation. We have numerous 'foes' such as the 3 Church of Scientology. The FDA is very 4 skitterish -- I have talked with Paul Leber twice 5 in the last several days," exclamation mark. "We 6 must not allow one day to elapse on follow-up, 7 flying to, investigating, etc., everything about 8 Prozac. Bob Zerbe can correct me for a wild 9 guess, but I would think we had twenty full-time 10 equivalents at least working just on Prozac 11 postmarketing safety and support and if necessary 12 we will stop everything else going on to provide 13 more. Every significant event about Prozac has 14 been a show stopper with twelfth floor meetings 15 immediately with Earl, Mel, etc. There cannot be 16 a fumble of even minor proportions on this one 17 because political pressure and perception and 18 public news, not science, could cause us to lose 19 this one." Five exclamation marks, signed Leigh, 20 right? 21 A Right. 22 Q Do you recall seeing this 23 document from Doctor Thompson? 24 A Yes, I do recall this 392 1 document. 2 Q What did you do in 3 response to this document? 4 A Nothing. 5 Q Do you see there where he 6 says "anything that happens in the UK can threaten 7 this drug in the US and worldwide"? 8 A Correct. 9 Q Do you understand what 10 he's talking about there? 11 A Not specifically, no. 12 Q How about generally? 13 A Generally, I think he's 14 indicating that data or results or interpretations 15 or analyses that are made in one country are very 16 rapidly transmitted worldwide to other countries. 17 But I don't know specifically what he's talking 18 about here. 19 Q Did you know that at that 20 time that Lilly was expending enormous efforts 21 fending off attacks? 22 A I know that there were a 23 number of people on television and in the 24 newspapers and other media attacking Lilly and 393 1 attacking Prozac; I was not particularly aware of 2 what efforts -- that the effort to respond were, 3 quote, enormous, unquote. 4 Q You weren't making an 5 enormous response at least, correct? 6 A Pardon me? 7 Q You weren't making an 8 enormous effort yourself? 9 A No. 10 Q In fact, the Teicher 11 article linking Prozac and suicidal ideation in 12 the American Journal of Psychiatry was published 13 only in February of 1990, correct? 14 A I'll accept that. I 15 don't recall when it was published, but if you say 16 it was then, I will certainly accept that. 17 Q If the Teicher article 18 hadn't been out but seven days, how could there 19 have been all of this enormous effort going on 20 that is discussed by Doctor Thompson? 21 A I think you would have to 22 ask Doctor Thompson what effort he was describing. 23 Q All right. The second 24 page of this document is a memo that you got two 394 1 minutes later from Doctor Thompson addressed just 2 to you, right? 3 A Correct. 4 Q A special memo from 5 Doctor Thompson? 6 A I wouldn't characterize 7 it as special, but it is an electronic message 8 from Doctor Thompson. 9 Q But it's especially for 10 you, you're the only one written there, aren't 11 you? 12 A I'll accept that. 13 Q He says, "I'm concerned 14 about reports I get re UK attitude toward Prozac 15 safety. Leber suggested a few minutes ago that we 16 using the CSM database to compare Prozac 17 aggression and suicidal ideation with other 18 antidepressants in the UK. Although he is a fan 19 of Prozac and believes a lot of this is garbage, 20 he is clearly a political creature and will have 21 to respond to the pressure. I hope Patrick 22 realizes that Lilly can go down the tubes if we 23 lose Prozac and just one event in the UK can cost 24 us that. You know my prejudice about Patrick, but 395 1 if I hear one more problem about not covering 2 Prozac safety in the UK, Allan, I'm going to be 3 really up in arms, Leigh," right? 4 A Right. 5 Q What did you do about 6 this memo? 7 A Nothing. 8 Q Did you discuss with 9 Doctor Thompson the issue that is the subject of 10 the February 7 memo directed to you? 11 A Not that I recall. 12 Q Did he ever follow-up 13 with you concerning this memo? 14 A I don't recall him 15 following up. 16 Q Did he seek you out and 17 say, "Allan, did you get my memo, what do you 18 think about this?" 19 A I don't remember him 20 seeking me out, no. 21 Q Is it your practice to 22 ignore memos from Doctor Leigh Thompson, on a 23 selective basis at least? 24 A No. 396 1 Q Why didn't you do 2 anything about this? 3 A I don't think this memo 4 requires any action on my part. 5 Q And you didn't take any 6 action? 7 A No. 8 Q Were you concerned about 9 the UK attitude toward Prozac safety as the vice 10 president of international medical? 11 A No. 12 Q Had you talked to Doctor 13 Leber about potentially using the CSM database to 14 compare Prozac aggression and suicidal ideation 15 with other antidepressants in the UK? 16 A I've never talked to 17 Doctor Leber. 18 Q Had you heard anything, 19 up to this time, about a suggestion by the Food 20 and Drug Administration that the CSM database -- 21 which is the British database, is it not? 22 A Correct. 23 Q Be used to compare Prozac 24 aggression and suicidal ideation with other 397 1 antidepressants in England? 2 A As I recall, this was the 3 first time that I knew about this. 4 Q Did you discuss this with 5 Doctor Thompson? 6 A No. 7 Q Was this ever done? 8 A I don't know. 9 Q A use of the CSM British 10 database to compare Prozac, suicidal ideation, and 11 aggressive behavior with other antidepressants in 12 England? 13 A I don't know. 14 Q Did you know anything 15 about Doctor Leber at that time being a fan of 16 Prozac? 17 A No, I simply know that 18 Doctor Leber ran the division that reviewed 19 neuropsychiatric drugs at the FDA. 20 Q You've never heard it 21 mentioned at Lilly by anyone there that they had a 22 friend in Doctor Leber? 23 A I personally did not hear 24 that, no. 398 1 Q Or that he was a fan of 2 Prozac? 3 A No. 4 Q Do you know whether or 5 not Doctor Leber consumes Prozac? 6 A No. 7 Q Do you have any knowledge 8 as to why he would be a fan of Prozac? 9 A No, I don't know Doctor 10 Leber, I've never met him, and so I really I can't 11 comment on these statements. 12 Q Have you ever seen 13 anything from Doctor Leber concerning this 14 allegation of Prozac and aggression and suicidal 15 ideation being, quote, garbage, end quote? 16 A No, I have never seen 17 anything like that. 18 Q Do you agree with Doctor 19 Leigh Thompson's characterization of employees of 20 the Food and Drug Administration, specifically 21 Doctor Paul Leber, as being a political creature? 22 A I don't know Doctor Leber 23 and I have no basis on which to agree or disagree 24 with Doctor Thompson's characterization. 399 1 Q Did you, at that time, 2 have any judgment concerning whether or not Lilly 3 would go down the tubes if Lilly lost Prozac? 4 A This is the first -- as I 5 recall, when I received this message, this is the 6 first time I had ever seen that kind of statement 7 made, and I did not agree with it. 8 Q Why? 9 A I did not see -- I did 10 not know on what basis Doctor Thompson was making 11 that statement, and as a company that is in many 12 countries with many products, I could not quite 13 understand what the statement may have meant. 14 Q In other words, you 15 didn't understand how the loss of one product at 16 Lilly would cause Eli Lilly and Company to go down 17 the tubes? 18 A That's correct. 19 Q Did you agree that one 20 event in England, the UK, could cost Prozac and 21 cause Lilly to go down the tubes? 22 A No. 23 Q Did you express this to 24 Doctor Leigh Thompson? 400 1 A No. 2 Q He says "you know my 3 prejudice about Patrick," correct? 4 A Correct. 5 Q What was his prejudice 6 about Patrick? 7 A I only know that there is 8 some personality disagreement between Doctor 9 Thompson and Doctor Keohane, and I have no idea on 10 what that is based. I don't believe they care for 11 one another as much as co-workers usually do. 12 Q Did you have an 13 impression that Doctor Keohane was not covering 14 Prozac safety in the UK? 15 A No. 16 Q In other words, Doctor 17 Leigh Thompson says "but if I hear one more 18 problem about not covering Prozac safety in the 19 UK, Allan, I'm going to really be up in arms," 20 doesn't he? 21 A That's what he says, yes. 22 Q But you didn't have the 23 judgment that he was not covering Prozac safety in 24 England? 401 1 A No, I did not have that 2 judgment. 3 Q Were you miffed or 4 irritated when you received this memo? 5 A No. 6 Q Why? 7 A Leigh, Doctor Thompson 8 was expressing his opinion, which he's certainly 9 entitled to do, and I read the memo, and that was 10 the end of my interaction on this memo. 11 Q If Doctor Leigh Thompson 12 had been really up in arms, could he have caused 13 problems for you, Doctor, within the corporation? 14 A I have no idea. 15 Q Has that ever occurred, 16 that Doctor Leigh Thompson has caused problems for 17 you within Eli Lilly and Company? 18 A Not that I'm aware of. 19 Q Do you know of any 20 criticism that Doctor Leigh Thompson has lodged 21 against you, sir? 22 A Not that I'm aware of. 23 Q Have you lodged any 24 criticism against Doctor Leigh Thompson within the 402 1 corporation? 2 A No. 3 MR. SMITH: Let's take a 4 quick break. 5 (SHORT BREAK TAKEN.) 6 (WEINSTEIN EXHIBIT NO. 24 MARKED FOR 7 IDENTIFICATION.) 8 Q (BY MR. SMITH) Exhibit 9 24 is apparently two communications in connection 10 with Prozac and suicide and label change, is that 11 not correct? 12 A And what? I didn't hear 13 your last -- 14 Q And label changes. 15 A Correct. 16 Q And is authored by Doctor 17 Leigh Thompson and dated September 12, 1990? 18 A Correct. 19 Q He starts out "urgent", 20 does he not? 21 A Correct. 22 Q Doctor Leber (with Doctor 23 Laughren on the speaker phone) called at 11:40 AM 24 and Dan Masica and John Heiligenstein joined me on 403 1 the speaker phone. Leber said that he was having 2 a meeting with Bob Temple 'in the next couple of 3 days' to 'bring him up to speed on suicidality.' 4 He wanted to have the odds-ratio analysis by 5 individual studies (we had faxed him the study 6 groups odds ratios August 6) and he said 'there 7 was disagreement about how much data we have to 8 feel secure.' I think this means he is being 9 pushed by Temple (and from Peck's comments 10 yesterday at least Peck is concerned) to change 11 the label. Doctor Leber said he would want the 12 completed report (draft is in the approval stage) 13 by 'next week,'" correct? 14 A Correct. 15 Q Who is Bob Temple? 16 A He is one of the 17 officials at the FDA. 18 Q All right. Is he senior 19 or junior to Doctor Paul Leber? 20 A I'm not an expert on the 21 organization; I believe he is senior, but I could 22 be incorrect. 23 Q It mentions also a fellow 24 by the name of Peck. Who is Peck? 404 1 A That's Doctor Bruce -- 2 no, Bruce Peck used to work for Lilly. I don't 3 remember the man's first name, but Doctor Peck was 4 a former employee of the FDA who retired last 5 year, who was one of the senior management people 6 in the FDA. 7 Q Would he have been senior 8 to Temple? 9 A I don't know. He might 10 have been, but I just don't know the structure. 11 Q You're addressed as a 12 principal addressee of this memo, are you not? 13 A Correct. 14 Q Did you know anything 15 about this movement for a label change within the 16 FDA? 17 A No. 18 Q Was this the first you 19 had heard of it? 20 A This must have been the 21 first I would have heard of it, yes. 22 Q He continues by saying, 23 "Actions: Dan Masica is carrying the odds-ratio 24 to Max to fax stat to Paul (he gave us permission 405 1 to use his fax 9280). Dan," as always, "had the 2 material in his hand when Paul called," 3 exclamation mark. "We will work on completing the 4 addendum report to FDA ASAP to get it in Leber's 5 hands very very quickly. The report only deals 6 with the controlled double-blind depression trials 7 and does not address what I believe their main 8 concern to be -- suicide acts from nondepressed 9 folks. We are working hard to get something on 10 the subject by September 25," correct? 11 A Correct. 12 Q Had you heard about a 13 possibility that the Food and Drug 14 Administration's main concern was that of suicide 15 in nondepressed folks? 16 A No, I had not heard that 17 before receiving this message. 18 Q Did you know that the 19 report that was being sent to the Food and Drug 20 Administration only dealt with Lilly controlled 21 double-blind depression trials? 22 A I may have known that, 23 but I was not involved in the preparation of what 24 they sent to the FDA. 406 1 Q This, of course, would 2 not include then, if it was just controlled 3 double-blind depression trials, all the trials 4 that Lilly had done concerning Prozac, would it? 5 A I'm sorry, I didn't hear 6 the beginning of your statement, could you -- 7 Q This would not include, 8 then, all the trials Lilly had done on Prozac? 9 A No, it only -- this memo 10 or this message says it includes only the 11 depression trials. 12 Q Right, and there were 13 many others trials on Prozac that had been run, 14 weren't there? 15 A On fluoxetine, yes. 16 Q It obviously wasn't going 17 to be called Prozac if it was going to be given 18 for an another indication? 19 A Pardon me? 20 Q It wasn't going to be 21 called Prozac -- 22 A I'm just saying 23 fluoxetine for precision's sake. 24 Q All right. But the point 407 1 is, there were other trials and other data 2 available concerning fluoxetine or Prozac clinical 3 trials done by Lilly that were not part of what 4 was being submitted to the FDA in the addendum 5 report? 6 A That's correct. 7 Q It goes on to say, "I'm 8 now very concerned that Temple et al. may force a 9 label change even before we get there on 25 10 September or, next worse, have this a fait 11 d'acompli when we arrive," correct? 12 A Correct. 13 Q Do you know anything 14 about any meeting that was going to occur on 25 15 September? 16 A I would be speculating. 17 That may well have been the FDA Advisory Committee 18 meeting on fluoxetine, but that would be just my 19 speculation. 20 Q That was 25 September 21 1991. 22 A Well, then I'm not sure 23 what the meeting was. 24 Q Well, there were several 408 1 meetings with Lilly employees and FDA employees 2 concerning the issue of suicidality and violent 3 aggressive behavior in connection with Prozac, 4 weren't there? 5 A I'll accept that. I was 6 not involved in the meetings and the planning for 7 the meetings, and so I would not have had a record 8 of all of the meetings that were held. 9 Q You went to some of those 10 meetings, didn't you? 11 A No. 12 Q Are you sure? 13 A The only meeting I recall 14 going to is the FDA Advisory Committee meeting. 15 Q He continues to say, 16 "That report must move swiftly through approval 17 and Doctor Leber's hands -- he is our defender," 18 end quote, correct? 19 A Correct. 20 Q Did you know anything 21 about Doctor Paul Leber being Lilly's defender 22 within the FDA? 23 A No. 24 Q Did you ever discuss that 409 1 with Doctor Leigh Thompson? 2 A No. 3 Q Or any other employee at 4 Lilly? 5 A No. 6 (WEINSTEIN EXHIBIT NO. 25 MARKED FOR 7 IDENTIFICATION.) 8 Q There was a Taiwanese 9 study done that compared Prozac and fluoxetine to 10 maprotiline, is that correct? 11 A Maprotiline. 12 Q Maprotiline, are you 13 familiar with that? 14 A No. 15 Q You're not familiar with 16 that study? 17 A No. 18 Q Are you familiar with the 19 fact that that study occurred? 20 A No. 21 Q Are you familiar with the 22 fact that that study revealed that seven 23 individuals taking Prozac and no individuals 24 taking maprotiline -- 410 1 MR. FREEMAN: We object 2 to this line of questioning here, and the matter 3 referred to is not a study. 4 Q -- attempted suicide, 5 you're not familiar with that? 6 A I'm not familiar with 7 that. 8 Q Are you familiar with 9 data reported from a Professor Lu in Taiwan where 10 he had compared these two substances and found a 11 difference in suicide, suicide attempts between 12 the two drugs? 13 A No, I would not 14 characterize that as data. 15 Q Why? 16 A Data implies that a 17 formal study was performed and no study was 18 performed. 19 Q Oh, your position is that 20 what was done in Taiwan wasn't a study, is that 21 what we're -- 22 A That's correct. 23 Q That's what we're going 24 to go through? 411 1 A That's correct. 2 Q You are familiar within 3 the situation in Taiwan where a physician in 4 Taiwan reported a difference in suicidality among 5 patients consuming those two drugs? 6 A Yes. 7 Q Was he going to write a 8 paper? What would we call it, since we can't call 9 it a study, what would we call it, Doctor? Pick 10 your word. 11 A His observations. 12 Q His observations. He was 13 going to write a paper on his observations, was he 14 not? 15 A I believe so. 16 Q What was he going to call 17 it, observations? 18 A I have no idea what he 19 was going to call it. 20 Q When did you first hear 21 about that, those observations? 22 A I don't remember the 23 precise date, but it was after that professor had 24 visited Indianapolis, sometime after that. 412 1 Q Are we going to call him 2 that professor or are we going to call him by 3 name? 4 A Call him by name, 5 Professor Lu. 6 Q When did Professor Lu 7 come to the United States? 8 A I don't recall the 9 specific day, it was within the last two plus 10 years, I believe. 11 Q How were you called in on 12 this? 13 A I was made aware, after 14 he had returned -- I believe returned to Taiwan, 15 that he had been here and presented his 16 observations to some of our central nervous system 17 and/or psychiatry experts. 18 Q Who was that? 19 A I believe Doctor Gary 20 Tollefson was present, I believe Doctor Charles 21 Beasley was present, and there may have been some 22 discovery research people also present, such as 23 Doctor Ray Fuller, but I'm not certain of that. 24 Q Doctor Wong? 413 1 A He may have been present. 2 Q Do you know who Doctor 3 Wong is? 4 A Yes. 5 Q What did you do in 6 connection with that? 7 A In connection with what, 8 I'm sorry? 9 Q That observation. 10 A I didn't do anything in 11 connection with the observation. 12 Q In response to the 13 observation? 14 A I did nothing in response 15 to the observation. 16 Q Did you talk to Professor 17 Lu about his observation? 18 A I talked to Professor Lu 19 about a number of factors a few months after, I 20 believe it was a few months after his visit to 21 Indianapolis; his observations were among the 22 things we talked about. 23 Q What did you talk about 24 in that connection? 414 1 A We talked about whether 2 his observations in fact constituted a scientific 3 study, and we agreed that they did not. 4 Q What was the deficiency? 5 A He had made observations 6 of two different patient groups at two different 7 times, not simultaneously. He had taken his 8 observations at some point earlier with 9 maprotiline, combined them at some point later 10 with fluoxetine, and drew conclusions based on 11 that experience. He had not done a head to head 12 randomized controlled trial between the two drugs. 13 Q Had he written a paper 14 concerning his observations? 15 A I'm not aware. He had 16 presented this information to the group that I 17 mentioned in Indianapolis when he was here; I 18 don't believe he had written a paper at that 19 point, but he may have had a manuscript prepared. 20 Q He was going to publish 21 something, wasn't he? 22 A He indicated he was going 23 to publish something. I don't think that tells me 24 whether he had written the paper yet, which was 415 1 your question. 2 Q Can you identify Exhibit 3 25? 4 A It appears to be, I 5 gather, the first page of a draft of a 6 publication. 7 Q It's something that at 8 least shows Doctor Lu as an author, does it not? 9 A Correct. 10 Q It has to do with suicide 11 attempts and fluoxetine treatments, does it not? 12 A Correct. 13 Q It appears to be entitled 14 "Suicide Attempts and Fluoxetine Treatment", does 15 it not? 16 A Correct. 17 Q The first page of this 18 exhibit indicates that there are thirty-four pages 19 transmitted via fax, does it not? 20 A Yes. 21 Q Have you ever seen the 22 entire document? 23 A I've never seen any of 24 this, that I recall. 416 1 (WEINSTEIN EXHIBIT NO. 26 MARKED FOR 2 IDENTIFICATION.) 3 Q Does Exhibit 25 and 4 Exhibit 26 appear to be, at least in the first 5 part, similar? 6 A Yes. 7 Q Could 26 be what's known 8 as an abstract of an article? 9 A Yes, it could be. 10 Q And could Exhibit 25 11 maybe just be the first page of the entirety of 12 the article? 13 A It could be. 14 Q You've never seen either 15 one of these documents? 16 A I don't recall having 17 seen them, no. 18 Q Do you know why in the 19 lower right-hand corner of Exhibit 26 there are 20 box numbers there? 21 A I don't see any box 22 numbers there. I don't have that on 26. 23 Q Does your document have a 24 Pz number on it? 417 1 A Yes. 2 Q Exhibit 26 has a Pz 3 number on it? 4 A Yes. 5 MS. ZETTLER: His copy of 6 26. 7 MR. MYERS: What is it, 8 what is the number he's holding? 9 MR. FREEMAN: The Pz 10 number is Pz 1989 1613. 11 MR. SMITH: I have 12 something that appears to be exactly the same with 13 a box number on it, but it is also stamped with 14 the same confidential stamp. 15 MR. MYERS: Right, and I 16 assume it was produced in part of that same 17 production; in other words, this is an additional 18 copy of the same thing. 19 MS. ZETTLER: I would 20 think so since it happens to be the same numbers 21 on it. 22 MR. SMITH: Maybe they 23 produce things in California differently. 24 MR. MYERS: Could be. 418 1 Q (BY MR. SMITH) So, do I 2 understand it, Doctor Weinstein, that you never 3 read the article authored by Professor Lu? 4 A I don't recall having 5 read the -- assuming that you're referring to this 6 thirty-four page telefax, I don't recall having 7 read that, no. 8 Q Do you recall reading the 9 abstract? 10 A I may have. I don't 11 recall specifically, but I may have read it. 12 Q You have several 13 criticisms of his observations, and my question 14 is, how would you be able to have criticized his 15 observations without reading the article? 16 A As I mentioned, the 17 criticisms that were raised were raised primarily 18 by the people with whom he met, and I've mentioned 19 who those individual were, and I was informed of 20 their criticisms of his presentation after he had 21 made the presentation. 22 Q Did you get an E-mail or 23 telex or something of that nature informing you of 24 their criticisms? 419 1 A I believe I was told 2 verbally. 3 Q Who told you that? 4 A I believe that I may have 5 heard that from people in Lilly Taiwan. 6 Q Who at Lilly Taiwan? 7 A I don't recall the 8 individual. 9 Q But you never attempted 10 to read the article to verify or to satisfy for 11 yourself any of the criticisms presented by your 12 people in Taiwan? 13 A They were not criticisms 14 by our people in Taiwan, they were criticisms, 15 scientific criticisms by people in Indianapolis. 16 Q Criticism by anybody 17 anywhere, you never read the article to verify 18 whatever criticisms were raised? 19 A As I said, I've not read 20 the thirty-four page document. I may have read 21 the abstract. 22 Q Have you ever done 23 anything to determine whether or not those 24 criticisms that were lodged to the article or to 420 1 the study or to the observations were legitimate 2 criticisms? 3 A I talked to the people 4 who had the opportunity to listen to the 5 presentation. 6 Q Other than that, have you 7 done anything? 8 A No. 9 Q So what did you do next 10 after you got these criticisms? 11 A That is really not the 12 sequence in which things happened. 13 Q Okay, then tell me what 14 really is the sequence in which things happened. 15 A I was informed, I 16 believe, at some time, I believe it must have been 17 in the first three months of 1992, that Doctor Lu 18 was very upset with Lilly because he felt that he 19 had not been treated well during his visit to 20 Indianapolis. I believe I was informed of this by 21 someone at Lilly Taiwan, as I mentioned earlier. 22 Q Now, when was the visit, 23 the original visit to Indianapolis? 24 A As I said earlier, I 421 1 don't recall specifically when it was. Sometime 2 after that visit I was informed by someone, who I 3 don't specifically remember, that Doctor Lu, who 4 was an important psychiatrist in Taiwan, and 5 apparently was an advocate of fluoxetine, was 6 upset with the company because of the interactions 7 he had had during the time he was here, apparently 8 with the individuals with whom he interacted. I 9 took it upon myself to visit him and try to make 10 amends and try to understand what he was concerned 11 about and tried to alleviate his concerns about 12 Lilly and his state of being upset about what his 13 treatment had been here. 14 Q Did you talk to him? 15 A I talked to him. 16 Q When did you go to 17 Taiwan? 18 A Sometime after his 19 visit. I travel seventy or eighty percent of the 20 time and I can't remember the specific visit. 21 Q How many times have you 22 been to the country of Taiwan? 23 A Ten or fifteen, at least, 24 in the last ten years. 422 1 Q Okay. So if you can't 2 remember when you visited him, can you remember 3 the substance of your discussion with him? 4 A Substance of my 5 discussion with him was to try to understand why 6 he had left Lilly Indianapolis feeling that he had 7 not been treated according to the way he wanted to 8 be treated. 9 Q What did he tell you in 10 that connection? 11 A He believed that his 12 scientific -- what he claimed to be his scientific 13 work had not been respected, and he felt that 14 apparently the personal interaction with the 15 people here had not been at the level that he 16 expected as a professor. 17 Q Did he name names? 18 A No, he didn't name 19 specific names. I've told you the people who were 20 there, as far as I know, but he did not name any 21 specific individual. As I recall, we talked about 22 that a lot. I also tried to explain to him that 23 one of the reasons that there had been a 24 scientific disagreement is that it was the 423 1 impression of the scientists who had met with him 2 that this was not a study, but that he had 3 collated observations performed at different 4 times, and that although his observations were 5 interesting, they really didn't constitute a 6 scientifically valid study. Over time, he agreed 7 with that and we talked about -- he then talked 8 about the possibility of whether he should do a 9 study properly designed and we agreed to work with 10 him, as necessary, to design that study. 11 Q Did the scientists at 12 Lilly think that Doctor Lu's observations were 13 incorrect? 14 A The scientists, I 15 believe, felt that his conclusions were incorrect. 16 Q What was his conclusion? 17 A His conclusion, as listed 18 in this abstract, indicates a higher rate of 19 suicide attempts in fluoxetine as opposed to 20 maprotiline. 21 Q Well, that was true, 22 wasn't it? 23 A No. 24 Q There were six people 424 1 that committed suicide who had taken -- or 2 attempted suicide who had taken Prozac, and none 3 had attempted suicide or committed suicide while 4 taking this other antidepressant, isn't that 5 correct? 6 A Those are his 7 observations. His conclusion that there was a 8 statistically significant difference between the 9 two drugs is not scientifically valid because 10 these were not as part of a study that was 11 randomized and prospective, and the drugs were not 12 studied at the same time. 13 Q But there were six people 14 that he observed, out of a number of people, that 15 had attempted or committed suicide, correct? 16 A Correct. 17 Q There were no people in 18 another group of people that he had observed that 19 had committed or attempted suicide, right? 20 A Right. 21 Q Those six people happened 22 to be out of a group of people that were taking 23 Prozac, right? 24 A Correct. 425 1 Q Those zero people 2 happened to be out of a group who were taking 3 maprotiline, correct? 4 A Correct. 5 Q So those observations, as 6 you term them, were correct, weren't they? 7 A Correct observations. 8 Q Your criticism was in 9 drawing any conclusions based on those 10 observations? 11 A Correct. 12 Q Did it take some period 13 of time to convince Doctor Lu that his conclusions 14 were incorrect? 15 A As I recall, we met for 16 two or three hours. 17 Q And did you discuss his 18 observations in detail? 19 A We discussed -- we did 20 not discuss the observations in detail; we 21 discussed his ability or a lack thereof to draw 22 conclusions from those observations. There was no 23 attempt to in any way question the observations, 24 as you stated. 426 1 Q You didn't have any 2 reason to disbelieve that his observations were 3 accurate, did you? 4 A We accepted his 5 observations. 6 Q Did you take anybody with 7 you to Taiwan? 8 MR. FREEMAN: From here? 9 MR. SMITH: Yes. 10 A Not that I recall, no. 11 Q Since you were not a 12 psychiatrist and not knowledgeable in connection 13 with -- specifically knowledgeable in connection 14 with Prozac and maprotiline, and he was a 15 psychiatrist and he was knowledgeable in these 16 antidepressants, how were you able to carry on a 17 scientific discussion with him in connection with 18 these issues? 19 A As I've tried to explain, 20 we were not discussing psychiatry, we were 21 discussing clinical trial design. It really was 22 not specific to a psychiatric drug as opposed to 23 any other classification of drug. The essence of 24 the discussion did not have to do with the 427 1 specific characteristics of maprotiline or Prozac 2 or any other antidepressant, it was whether 3 observations made at separate times could 4 legitimately or acceptably lead to conclusions 5 that were being drawn. 6 Q Did you ask him to not 7 publish his observations? 8 A No. 9 Q Did anybody at Lilly 10 suggest that he not publish his observations? 11 A I'm not aware that 12 anybody suggested that he not publish, and we had 13 no ability to prevent anybody from publishing. 14 Q How long were you in 15 Taiwan on that particular trip? 16 A I believe I was there a 17 very brief period of time, but again, with 18 respect, I don't remember every trip I've taken 19 over the last eleven years. I think I was there a 20 very short period of time. 21 Q Twenty-four to 22 forty-eight hours? 23 A It could have been, yes. 24 Q Have you ever been to 428 1 Taiwan on other occasions in regards to Prozac? 2 A I believe I was there 3 within the last year and a half to meet with 4 Doctor Lu again as we began to finalize plans for 5 the study which he has performed. 6 Q Has this new study or the 7 study that he agreed to start after this trip that 8 you made in early 1992 begun? 9 A Yes. 10 Q How many people are 11 enrolled in the study? 12 A I don't know. I don't 13 keep track of enrollments. 14 Q Who is the medical 15 monitor on that study? 16 A The medical director 17 responsible for that study is Doctor Robert Askian 18 in Australia, and he works with the medical 19 manager in Taiwan, whose name is P.L. Wu, W-U. 20 Q What's the objective of 21 that study? 22 A The objective is, as 23 Doctor Lu had indicated, to compare the efficacy, 24 safety, and suicidality in fluoxetine treated 429 1 depressed patients as opposed to maprotiline 2 treated depressed patients. 3 Q And has that study begun? 4 A I believe it has begun. 5 Q Has that study been 6 completed? 7 A No. 8 Q Do you know how long that 9 study is scheduled; in other words, how many 10 patient weeks? 11 A I don't know the 12 specifics. I was not involved in the specific 13 design of the study. He worked with the people 14 I've mentioned and with the psychiatrists here in 15 Indianapolis. 16 Q Which psychiatrists here 17 in Indianapolis? 18 A I think -- well, he did 19 not work personally with them, but the 20 communications were with a person named Doctor 21 Pande, P-A-N-D-E. 22 Q Anybody else? 23 A That's all that I'm aware 24 of. 430 1 Q Do you know how many 2 patients were scheduled to be enrolled? 3 A No. I know it was a 4 sizeable number, but I don't know the number. 5 Q How did you agree to 6 commit to this study if you don't know anything 7 about the study? 8 A The commitment to do the 9 study is managed by the people who are closer to 10 them. It's not my personal commitment to do the 11 study, it's the commitment of Lilly Research 12 Laboratories, and our people in the area work with 13 investigators in all therapeutic classes to design 14 studies and decide the size of the design of the 15 study, the protocol, the case report forms, 16 et cetera. That is not one of my specific 17 responsibilities. 18 Q Wasn't the result of your 19 trip down there that Doctor Lu was hired to 20 conduct another study on Prozac or a study on 21 Prozac? 22 A I wouldn't use the word 23 hired, but he agreed to do another study -- a 24 study on Prozac. 431 1 Q You went down there with 2 the authority to secure his services to do a study 3 on Prozac? 4 A I have that authority. 5 That was not the purpose of my trip, but I have 6 that authority, yes. 7 Q And you exercised that 8 authority there at that meeting? 9 A Correct. 10 Q Did you discuss how many 11 patients would be enrolled in the study? 12 A No. 13 Q Did you discuss anything 14 about the design of the study? 15 A The only thing we 16 discussed was that it be an appropriately designed 17 study with an appropriate number of patients so 18 that valid scientific conclusions could be drawn, 19 and that he, Doctor Lu, would work that out with 20 the specific individuals at Lilly Research 21 Laboratories who have that responsibility, such as 22 psychiatrists, et cetera. 23 Q Did you retain him to do 24 that study before or after he agreed not to 432 1 publish the study, the previous observations? 2 A There was never any 3 agreement not to publish the previous 4 observations. 5 Q Oh, there wasn't? 6 (WEINSTEIN EXHIBIT NO. 27 MARKED FOR 7 IDENTIFICATION.) 8 Q What does that say? Read 9 it. 10 A It says he will not 11 present or publish his fluoxetine data. 12 Q What does it say before 13 that, Doctor? 14 A Mission successful. 15 Q You went down there then 16 with the mission that Professor Lu not present or 17 publish his fluoxetine versus maprotiline suicidal 18 data, didn't you? 19 A No. 20 Q Then why would you say 21 mission successful? 22 A Because we had an unhappy 23 customer, we had an unhappy significant opinion 24 leader who left Indianapolis very concerned about 433 1 his treatment here, I was called, as I mentioned, 2 by our employees in Taiwan who were concerned that 3 this man felt he had been mistreated, and I 4 volunteered to go to Taiwan and try to make this 5 man happier and less angry at Eli Lilly, and that, 6 in fact, was accomplished. 7 Q You don't say a word 8 about that in this exhibit, do you? 9 A No. 10 Q You say, "Mission 11 successful," and then you say, "Professor Lu will 12 not present or publish his maprotiline suicidality 13 data. We will work with him in the very near 14 future to design a prospective randomized, 15 controlled, double-blind study of fluoxetine 16 versus maprotiline. Regards, Allan," correct? 17 A Correct. 18 Q Is it your testimony here 19 today, Doctor Weinstein, that when you say 20 "mission successful", you're not referring to the 21 fact that Professor Lu would not publish or 22 present his fluoxetine suicidality data? 23 A Correct. 24 Q And that when you meant 434 1 mission successful, you meant that he was unhappy 2 and you had made him happier, and that he didn't 3 feel slighted anymore, is that your sworn 4 testimony here today? 5 A Correct. 6 Q Why didn't you say that 7 in this memorandum? 8 A I don't recall why I 9 didn't say something two and a half years ago. 10 Q Did you recall at the 11 time why you didn't say that? 12 A I'm not sure I understand 13 the question. 14 Q You say you don't recall 15 it now. Do you remember that at the time you had 16 a particular reason not to give the details 17 concerning making him a happy customer? 18 A Perhaps I'm not as 19 expressive as I should be in written 20 communication, I don't recall. 21 Q Perhaps not. Why did you 22 direct this memo to Vaughn Bryson? 23 A He was one of many 24 addressees. 435 1 Q Why did you direct this 2 memo to Vaughn Bryson? 3 A I directed this memo to 4 the members of the group that met on Tuesday 5 morning, because it was a Tuesday morning meeting 6 that this was discussed that this man was upset 7 about his treatment, and I volunteered at that 8 Tuesday morning meeting, in front of these 9 individuals, to go to Taiwan and try to get him 10 unupset, if that's an appropriate word. 11 Q But you don't say that in 12 connection with your mission successful statement, 13 do you? 14 A I don't say that. I'm 15 sure all of them recognize that, since that's what 16 I volunteered for. 17 Q Is it your testimony that 18 Mr. Bryson, the Chief Executive Officer and 19 President of Eli Lilly and Company, was concerned 20 about Professor Lu being a dissatisfied customer 21 and that this has been discussed with him on the 22 Tuesday morning Prozac meeting? 23 A It is my testimony that 24 Mr. Bryson was aware of the fact that Professor Lu 436 1 was a dissatisfied customer, yes. 2 Q Was he also aware of the 3 fact that Professor Lu had data or observations 4 that were harmful to Eli Lilly and Company? 5 A I suspect he was also 6 aware of the fact that those observations had been 7 made. 8 Q And those observations 9 would not be good observations as far as Lilly was 10 concerned, would they? 11 A I don't really know. 12 Honestly, I think that the scientific community 13 would have to judge the validity or invalidity of 14 those data. 15 Q Why didn't you let them, 16 then? 17 A I did. I had no 18 involvement in Professor Lu's decision not to 19 publish or present his data. I have no ability to 20 control him. 21 Q You went over there, 22 flew -- how many miles is it to Taiwan? 23 A Many. 24 Q You've been there fifteen 437 1 times, tell us. 2 A I generally don't count 3 the miles on my trips. 4 Q You don't have any idea 5 how far it is? How long does it take to fly over 6 there? 7 A Probably fourteen hours. 8 Q You sat in a plane for 9 fourteen hours, you're a vice president of Lilly 10 Research Labs, to talk to a fellow over in Taiwan 11 about a slight that he apparently felt by virtue 12 of being here in Indianapolis, is that correct? 13 A Correct. 14 Q And then you reported 15 back to the President and Chief Executive Officer 16 of the corporation, Doctor Bryson, correct? 17 A Mr. Bryson, yes. 18 Q Mr. Bryson. You reported 19 to the President of Lilly Research Labs, Mr. Mel 20 Perelman -- 21 A Correct. 22 Q -- concerning your 23 activity? 24 A Correct. 438 1 Q What you told them in 2 your memo wasn't that Doctor Lu no longer felt 3 slighted, what you told them was that your mission 4 was successful and that he would not publish or 5 present his data, didn't you? 6 A Those are the words that 7 are on the message, yes. 8 Q Do you think this is, in 9 looking at it, a poor choice of words on your 10 part? 11 A You've interpreted it as 12 a poor choice of words on my part and 13 misinterpreted what the message says, so I guess 14 it must have been a poor choice of words on my 15 part. 16 Q This was to be a 17 prospective trial? 18 A The one that's planned? 19 Q Yes. 20 A Yes. 21 Q And then you have 22 prospectively compare Prozac and maprotiline to 23 see if it increases or decreases suicidality in 24 human beings? 439 1 A Correct. 2 Q And that's going to be a 3 randomized, controlled, double-blind trial? 4 A Correct. 5 Q You didn't work out any 6 of the details other than what you wrote here? 7 A That's correct. 8 Q Have you seen the 9 protocol in connection with that? 10 A No, the protocol, during 11 the period of design of the protocol, the protocol 12 came to Indianapolis on many occasions, but I was 13 not personally involved in the protocol. 14 Q Was that protocol 15 submitted to the Food and Drug Administration? 16 A It's highly unlikely that 17 it was. 18 Q The United States Food 19 and Drug Administration? 20 A I don't know for certain, 21 but it's highly unlikely that it would have been 22 submitted. 23 Q Why is that, sir? 24 A Because it's not required 440 1 under any regulations that the study of two 2 marketed products, used within their label, be 3 submitted to the US FDA, and in Taiwan both 4 fluoxetine and maprotiline are approved and they 5 will be used -- they are being used in the 6 appropriate patient population at the approved 7 dosages. 8 Q Is the design of the 9 study such that it examines depressed individuals, 10 or does it exclude depressed individuals? 11 A No, I believe it is a 12 study in depression, depressed individuals. 13 Q Depressed suicidal 14 individuals? 15 A No, depressed 16 individuals. 17 Q To determine whether or 18 not there is any difference in the suicidality, 19 prospectively? 20 A To prospectively look at 21 efficacy, safety, and suicidality. 22 Q Is there a specific 23 suicidal inventory or scale or measurement in 24 connection with the protocol? 441 1 A Yes, there is. I'm not 2 qualified, and if you ask me what it is, I can't 3 tell you, but I know that it was specifically 4 added at the request of Doctor Lu and it was 5 worked out with our psychiatrists here, and there 6 is a specific assessment of suicidality that is 7 part of this study. 8 Q Do you recall who the 9 psychiatrist was here in the United States that 10 assisted in working that out? 11 MR. FREEMAN: He said 12 Doctor Pande. 13 A I believe it was Doctor 14 Pande. 15 Q Do you recall how long 16 that study was to last? 17 A From the first -- do you 18 mean from the entry of the first patient until -- 19 Q Yes, sir. 20 A Many months, but I don't 21 know specifically. There were a large number of 22 patients to be entered in this study, as I recall. 23 Q Did you and Doctor Lu 24 discuss any of the details of the plan other than 442 1 what's reflected in exhibit -- what is it? 2 A 27. 3 Q Yes. 4 A No, I personally did not 5 discuss any of those details, other than, as I 6 mentioned, that we agreed that the study should be 7 of appropriate size so that any conclusions that 8 would be drawn would be statistically valid. 9 (WEINSTEIN EXHIBIT NO. 28 MARKED FOR 10 IDENTIFICATION.) 11 Q Exhibit 28 appears to be 12 a document authored by David Wong, does it not? 13 A Correct. 14 Q And who is he? 15 A He's one of the research 16 scientists. 17 Q Is this the same Doctor 18 Wong that was responsible for the development of 19 Prozac? 20 A Yes. 21 Q It's directed to several 22 individuals at Lilly, is it not? 23 A Yes. 24 Q And this would have been 443 1 in connection with his visit, Doctor Lu's visit? 2 A Correct. 3 Q Doctor Wong has testified 4 in fact, Doctor Weinstein, that Doctor Lu and his 5 associate had dinner in Doctor Wong's home during 6 this trip. 7 A I accept that. 8 Q You're not copied on 9 this, but this says, "Both Doctors Lu and Ko 10 expressed that they were glad to come and discuss 11 the results with Doctors Beasley and Tollefson. 12 They have indicated to me that they follow the 13 methodology to analyze the data according to that 14 used and published by Doctor Beasley and 15 colleagues. They also indicate to increase the 16 size of the study as suggested to them. 17 "I believe that they like 18 to maintain a contact with our medical colleagues 19 whom they have high regard and experience in 20 dealing with the subject. 21 "Finally, they enjoyed an 22 evening of relaxation with other friends in my 23 home. 24 "This morning, they took 444 1 a taxi to the airport themselves and on their way 2 to Taiwan. 3 "This serves as my brief 4 report. Best regards, David," correct? 5 A Correct. 6 Q "P.S. Clarification 7 emphasizes that 'they'll re-analyze their data by 8 following Doctor Beasley's published methods,'" 9 correct? 10 A Correct. 11 Q It appears to me from 12 reading this that at least Doctor Wong is not 13 reporting any slight on the part of Doctor Lu's 14 feelings. 15 A That's correct. 16 Q Well, who expressed to 17 you that Doctor Lu felt slighted? 18 A As I mentioned, I don't 19 recall the specific individuals, but it was people 20 at Lilly Taiwan. 21 Q But it appears that the 22 individual here at Lilly Indianapolis felt that 23 they enjoyed themselves? 24 A I accept that that is 445 1 Doctor Wong's conclusion from his visit with 2 them. Doctor Wong did not talk to me and I did 3 not talk to him about this. My contact, as I 4 mentioned, was subsequent to their leaving from 5 people in Lilly Taiwan who interpreted the visit, 6 based on Doctor Lu's comments, very differently 7 than Doctor Wong apparently has. 8 Q So, at best, there is a 9 difference in interpretation of what Doctor Lu's 10 feelings were, correct? 11 A Well, obviously Doctor 12 Wong here has interpreted their feelings 13 differently than the staff at Lilly Taiwan, that's 14 correct. 15 Q Did you discuss with 16 Doctor Lu the fact that he had been in Doctor 17 Wong's home while visiting here in Indianapolis? 18 A No. 19 Q Did you, in fact, know 20 that he had been in Doctor Wong's home for dinner 21 when you went and visited with Doctor Lu in 22 Taiwan? 23 A I doubt it; I suspect 24 not. 446 1 Q You know, however, that 2 Doctor Wong is an extremely cordial individual? 3 A Certainly. 4 Q And that Doctor Wong 5 would not be an individual who would likely offend 6 another, correct? 7 A Correct. 8 Q Were you surprised when 9 you heard that Doctor Lu was offended from your 10 Taiwanese affiliate? 11 A Yes, I was surprised. 12 (WEINSTEIN EXHIBIT NO. 29 MARKED FOR 13 IDENTIFICATION.) 14 Q Have you had an 15 opportunity to review Exhibit 29? 16 A Yes. 17 Q It appears that this is a 18 document dated April 30, 1992 reflective of a 19 meeting with Doctor Lu and individuals at the 20 Lilly affiliate in Taiwan, is that right? 21 A No. 22 Q Well, what is it, then? 23 A I believe it reflects a 24 series of interactions over the course of two 447 1 weeks between Michael Chen, who was the former 2 medical manager at Lilly Taiwan, and Professor Lu. 3 Q What did I say that was 4 wrong? 5 A A meeting. 6 Q Okay, I apologize, 7 several meetings, or discussions or 8 communications. 9 A I don't know if they were 10 meetings, they may have been on the telephone, but 11 some kind of communication. 12 Q Contacts? 13 A Yes. 14 Q You're an addressee on 15 this document, are you not? 16 A Yes. 17 Q Did you read it? 18 A Yes. 19 Q Was this accurate, you 20 had been to Taiwan to make Doctor Lu feel better? 21 A It must have been, yes. 22 Q Apparently there was -- 23 and this is broken down into Professor Lu's 24 comments and Lilly's response, right? 448 1 A Correct. 2 Q And would Lilly's 3 response that is reflected here been a response by 4 Doctor Chen, the head of the medical division of 5 Lilly in Taiwan? 6 A Yes. 7 Q Or would he have been 8 clearing this through Indianapolis? 9 A No, he would not have 10 cleared, these would be direct communications 11 between him and Professor Lu. 12 Q Did you have any 13 conversations in connection with these matters 14 that are mentioned here by Doctor Chen as the 15 matter progressed? 16 A I don't recall any. 17 Q Was he keeping you 18 advised by telephone? 19 A No, absolutely not; I 20 didn't speak with him by telephone. 21 Q Why did you say, no, 22 absolutely not? 23 A Because I just recall 24 I've never received a telephone call from Michael 449 1 Chen. 2 Q Or from Taiwan? 3 A I have received them from 4 Taiwan; as I mentioned, that's how I found out 5 there was concern about the initial Indianapolis 6 visit, but I specifically recall that I've not 7 spoken on the phone with Michael Chen. 8 Q Does Michael Chen speak 9 English? 10 A Yes. 11 Q Apparently on April 14, 12 Professor Lu, "I'm fairly happy with the protocol 13 faxed by Doctor Weinstein," correct? 14 A Correct. 15 Q So we can pin down at 16 least from that, that by April 14 you had not only 17 calmed him down, but had faxed him a protocol? 18 A Correct. 19 Q Do you remember where you 20 got that protocol? 21 A It was here in 22 Indianapolis. 23 Q But this was a 24 prospective study examining suicidality with a 450 1 specific suicidality scale, and I believe our 2 testimony up-to-date was that Lilly didn't have 3 anything in existence at this time. 4 A No. 5 Q So it would have had to 6 have been -- my judgment is, and correct me if I'm 7 wrong, this protocol would have had to have been 8 something that was designed for Professor Lu? 9 A No. As I recall this, we 10 sent a protocol that was a comparative trial, that 11 would describe a comparative trial between 12 fluoxetine and maprotiline, and that we asked 13 Doctor Lu to add or delete those elements in the 14 protocol which he felt would be appropriate for 15 the study he wanted to design. 16 Q The prospective 17 double-blind -- 18 A Prospective study. 19 Q -- comparison of the two 20 drugs specifically examining suicidality 21 prospectively? 22 A Correct. 23 Q On April 14 it says he's 24 fairly happy with the protocol, right? 451 1 A Right. 2 Q Then by April 17 he says, 3 "I'm considering now not to conduct the study 4 because it will take more than two years to 5 complete and will cost a lot of money, 6 furthermore, the topic is not my personal 7 interest." Do you see that? 8 A I see that. 9 Q Did I read that 10 accurately? 11 A Yes. 12 Q Did you know that this 13 area was not his personal interest? 14 A No, that was not -- as I 15 mentioned, the only contact I had with Professor 16 Lu up to that time was my personal meeting with 17 him sometime before April 14, and he did not 18 convey that statement to me. 19 Q The Lilly response to 20 Doctor Lu's concerns expressed on April 14 was, 21 "Don't worry about the cost. You may include 22 elements which are of interests to you, and if 23 possible incorporate with other medical centers to 24 shrink trial period. We will arrange for you to 452 1 visit Doctor Weinstein and Tollefson and discuss 2 the study after APA conference," correct? 3 A Right. 4 Q Did you have any idea how 5 much the study would cost -- 6 A I doubt it. 7 Q -- at that time? 8 A I doubt it. 9 Q Did you have any idea how 10 much this study would cost Lilly when you went to 11 Taiwan and agreed that he conduct this study? 12 A No. 13 Q Do you know to this day 14 how much this study will cost? 15 A I believe it will cost 16 several hundred thousand dollars. 17 Q How did you come to that 18 judgment? 19 A Because Doctor Lu 20 submitted a budget. 21 Q And was it closer to one 22 hundred thousand or nine hundred thousand? 23 A It's probably closer to 24 nine hundred thousand than one hundred thousand. 453 1 Q Could it have exceeded 2 nine hundred thousand? 3 A I don't know, it could 4 have, but again, I am aware of the fact that the 5 study, as finally designed, would be many hundreds 6 of thousands of dollars to perform based on the 7 budget he had requested. 8 Q Is this an expensive 9 study as compared to other Prozac clinical trials 10 or studies, or inexpensive? 11 A I can't make that 12 judgment, I'm not familiar with -- I've not been 13 involved in the budgeting part of Prozac studies. 14 My impression is that this would not be terribly 15 expensive at this time for a Prozac study. 16 Q Do you know of any other 17 study where the principal investigator in the 18 design of the study was advised not to worry about 19 the cost of the study? 20 A That advice was given by 21 Michael Chen, and I think you would have to ask 22 him what was behind his statement. That was not a 23 statement that came from Indianapolis. 24 Q That's not what I asked 454 1 you, Doctor. 2 MR. SMITH: Could you 3 repeat the question, please? 4 REPORTER: (READING) Do 5 you know of any other study where the principal 6 investigator in the design of the study was 7 advised not to worry about the cost of the study? 8 A No. 9 Q The Lilly response of 10 April 17 also indicates, "We will arrange for you 11 to visit Doctor Weinstein and Tollefson and 12 discuss the study after APA conference." Did you 13 meet with him? 14 A Not that I recall. 15 Q Don't you think you would 16 recall had you met with him? 17 A Yes. 18 Q Then on April 21, 19 apparently Doctor Lu's comments were, "I'm 20 hesitating in deciding whether I should publish 21 the previous finding. I'd like to know what's the 22 impact to your company if I publish it." 23 Lilly's response was, 24 "The enormous impact will come from the cult 455 1 rather than the publication. We can't imagine how 2 they will utilize your information, but we know 3 that it's their way to extort people with the 4 publications like Teicher's," correct? 5 A Correct. 6 Q Did Doctor Chen discuss 7 that response with you in any way? 8 A No. 9 Q Did you feel that 10 publication of Doctor Lu's observations would have 11 an enormous impact? 12 A No. 13 Q Did you think it would 14 have any impact if he published his observations? 15 A The only impact I felt 16 they would have would be on Doctor Lu because they 17 would have been an embarrassment to publish. 18 Q On April 26, apparently 19 Professor Lu comments, "What are perceptions of 20 Doctors Haski and Weinstein regarding our previous 21 discussions?" Who is Haski? 22 A He's the Lilly regional 23 medical director for Asia, he's based in 24 Australia. 456 1 Q Lilly's response was, 2 "They," meaning you and Haski, "seem satisfactory 3 to have your agreement about conducting a 4 well-designed study, and you can publish whatever 5 you find after the study is completed," correct? 6 A Correct. 7 Q Did you say that, Doctor 8 Weinstein? 9 A I probably did, yes. 10 Q The document goes on to 11 say in this letter to Doctor Tollefson, "We would 12 appreciate it if you could arrange Doctor David 13 Dunner (and/or yourself or Doctor Beasley) to meet 14 Professor Lu personally during the APA, and 15 reinforce the impact will be if flawed information 16 is published. The bottom line is to convince him 17 to conduct a well-designed study which could 18 include his personal interests," correct? 19 A Correct. 20 Q Do you think Mr. Chen is 21 talking about the impact to Doctor Lu or the 22 impact to Lilly if flawed information were 23 published? 24 A I don't know what 457 1 Mr. Chen is talking about, you would have to ask 2 Mr. Chen. 3 Q You don't have any 4 judgment one way or the other -- 5 A No. 6 Q -- to what he's referring 7 in that statement? 8 A No. 9 (SHORT BREAK TAKEN.) 10 Q (BY MR. SMITH) Is it 11 your testimony, Doctor, that you did nothing in 12 any attempt to forestall the publication of Doctor 13 Lu's observations? 14 A Other than convince him 15 that his observations were not a valid scientific 16 study. 17 Q So it was your intent to 18 forestall publication? 19 A No. It was my intent to 20 point out to Doctor Lu that his observations did 21 not constitute a valid study. 22 Q Do you deny that you were 23 attempting to forestall publication of his data? 24 A I cannot forestall 458 1 publication of anybody's data. 2 Q That you were attempting 3 to? 4 A I was pointing out to 5 Doctor Lu that his observations did not constitute 6 a proper study. 7 Q In that, were you 8 attempting to forestall publication of his data? 9 A No, I was pointing out 10 that he would perhaps cause himself an 11 embarrassment if he presented information like 12 that. 13 (WEINSTEIN EXHIBIT NO. 30 MARKED FOR 14 IDENTIFICATION.) 15 Q It appears that Weinstein 16 Exhibit 30, dated March 17, 1992, has to do with 17 Professor Lu and the Taiwan fluoxetine issues and 18 is a note to Gary Tollefson authored by you and 19 Rob Haski? 20 A That's correct. 21 Q The last sentence of the 22 next to the last paragraph says, quote, "Because 23 of the extreme sensitivity of the matter and the 24 fact that Professor Lu is one of the top Prozac 20 459 1 prescribers in Taiwan, we are maintaining close 2 contact to obtain as much additional information 3 as we can in regard to the study in question and 4 to ascertain how we can forestall any premature 5 publication of what clearly looks like flawed 6 data," end quote. Correct? 7 A Correct. 8 Q In that document you do 9 write that you were attempting to ascertain how 10 you could forestall any premature publication of 11 the data? 12 A I don't write that, 13 Doctor Haski writes that. 14 Q It's got Allan Weinstein 15 and Robert Haski on it, doesn't it? 16 A It's also based on the 17 source coming from Doctor Haski's E-mail message 18 account, and if you look at the time of day, you 19 will realize that it's authored in Australia since 20 I'm not in the habit of writing E-mail messages at 21 1:48 AM. I recall that Doctor Haski sent a 22 message to Gary Tollefson after we had had 23 discussions when I was visiting Sydney, and these 24 are Doctor Haski's words. He has included my name 460 1 because we worked together, but those are not 2 words that I wrote. 3 Q Oh, really? 4 A Yes. 5 Q Did you write Doctor 6 Haski or send an E-mail to Doctor Haski when you 7 got this and say, "Hey, those are not my words, 8 I'm not doing anything to forestall any 9 publication"? 10 A I don't recall. I 11 probably saw this after it had been sent while I 12 was still in Australia. 13 Q Weren't you in Australia 14 with him? 15 A Correct. 16 Q Didn't he clear this with 17 you when he wrote it? 18 MR. FREEMAN: When he 19 wrote it? 20 MR. SMITH: He wrote it. 21 Q (BY MR. SMITH) When it 22 was written? 23 A No, he would not be in 24 the habit of clearing his messenger messages with 461 1 me. 2 Q It's got your name on it, 3 it says, "Regards, Allan Weinstein and Rob Haski," 4 doesn't it? 5 A He is referring, if you 6 look at the beginning, we have had further 7 discussions with Michael Chen, and I do recall 8 some telephone conversation with Michael Chen at 9 that time. Rob Haski then sat down and wrote a 10 message in which he made three points based on 11 those telephone conversations and signed both of 12 our names, which I did not object to, he sends 13 many messages when I am down there when we discuss 14 matters, but I did not write these words. These 15 are Doctor Haski's words and it's his 16 characterization. 17 Q Was his characterization 18 incorrect? 19 A It is incorrect as far as 20 I'm concerned. 21 Q He refers to Professor 22 Lu's observations as a study, doesn't he? 23 A I'm sorry, I don't see 24 where that is. 462 1 Q In the last sentence -- 2 A Yes, he does. 3 Q -- of the last full 4 paragraph. 5 A He does. 6 Q He says, "in fact, we 7 believe Professor Lu has opportunistically taken 8 the interest in suicide ideation because it is 9 topical and is to him a chance to advance his 10 career and standing," doesn't it? 11 A That's what it says. 12 Q Do you agree with that? 13 A No. 14 Q Did you voice any 15 objection to Mr. Haski in that statement? 16 A I don't recall 17 specifically our conversations following this. 18 Q He says "we believe", 19 doesn't he? 20 A Yes. 21 Q Did you and he discuss 22 this? 23 A We discussed -- because 24 he has responsibility for Taiwan, we discussed the 463 1 situation with Doctor Lu, Professor Lu on multiple 2 occasions. I don't remember specifically having a 3 discussion with him that deals with, quote, 4 opportunistically taken an interest in suicide 5 ideation, et cetera. 6 Q So, for accuracy, 7 obviously -- is it Mister or Doctor Haski? 8 A Doctor. 9 Q Doctor Haski believes 10 that Professor Lu is opportunistically taking the 11 interest in suicidal ideation, but you don't 12 believe it? 13 A I don't believe that. I 14 mean, you would have to speak with Doctor Haski 15 about what has led him to believe this, but I 16 don't -- 17 Q You see, the reason I'm 18 asking you about it, Doctor Weinstein, is because 19 he says "we", and he signs your name and his name 20 to it. 21 A I understand that. 22 Q And he says, "We are 23 maintaining close contact to obtain as much 24 additional information as we can in regard to the 464 1 study in question to ascertain how we can 2 forestall any premature publication of what 3 clearly looks like flawed data," correct? 4 A Correct. 5 Q You can understand my 6 thinking that you agreed with that, can you not? 7 A I can understand your 8 thinking, but perhaps I could remind you of the 9 fact that I mentioned earlier that I personally do 10 not have close contact with these studies and that 11 the individuals closer geographically are the ones 12 who maintain close contact. He may have used the 13 word we, but I think it's abundantly clear from 14 the way I've operated in my job that I don't 15 maintain close contact in these matters, and that 16 I defer responsibility to those who are closer. 17 Q Well, you're faxing him, 18 according to Exhibit 29, the protocol -- 19 A That's correct. 20 Q -- yourself. 21 A Because the protocols are 22 present in Indianapolis, and since I was the only 23 representative of Indianapolis who met with Doctor 24 Lu at that time in Taiwan, I took the 465 1 responsibility to come back here and ask someone 2 to fax him a protocol. 3 Q Well, it was obviously 4 faxed under your instructions and directions? 5 A Correct. 6 Q And he says -- or Doctor 7 Lu's comments purportedly say "I'm fairly happy 8 with the protocol faxed by Doctor Weinstein", 9 right? 10 A Yes. 11 Q Not by Lilly in 12 Indianapolis? 13 A I don't know who 14 specifically faxed that protocol. It may have 15 well come from my office. 16 Q Did you recruit Doctor Lu 17 to do this study? 18 A Recruit, I don't know 19 what you mean by recruit Doctor Lu to do this 20 study. 21 Q I think you used the term 22 earlier this week. 23 A I may have in another 24 context. As I mentioned to you, when we met with 466 1 Doctor Lu, we talked about the observations he had 2 made, we talked about the possibility of 3 performing a prospective, randomized, controlled 4 double-blind study, and he asked did we have a 5 protocol that he could work from, and I said I 6 will find out and send you one when I get back to 7 Indianapolis, which I did. 8 Q I thought a protocol had 9 to be designed because this was something that had 10 never been done before? 11 A I sent him a protocol 12 that was a safety and efficacy protocol looking at 13 fluoxetine versus maprotiline, and specifically 14 said to him add those elements which are of 15 interest to you, take out those elements which you 16 do not feel are necessary, and we will agree upon 17 a protocol that you can work from. 18 Q Have you ever done this 19 with any other investigator before? 20 A Absolutely. 21 Q Sent them a protocol and 22 given them carte blanche to include