1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT DIVISION ONE (1) 2 3 JOYCE FENTRESS, ET AL. PLAINTIFFS 4 5 VS. DEPOSITION FOR PLAINTIFFS 6 7 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 8 * * * * * * * * * * 9 10 DEPONENT: DR. ROBERT ZERBE 11 DATE: MAY 13, 1994 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 20 (502) 589-2273 Page 1 1 * * * * * * * * * * 2 3 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 4 INDIANAPOLIS DIVISION 5 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 6 Litigation ) 7 * * * * * * * * * * 8 NO. 91-02496-A 9 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 10 V. ) DALLAS COUNTY, TEXAS ) 11 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 12 * * * * * * * * * * 13 NO. 92-14775-E 14 RICHARD HAROLD CROSSETT, JR., ) IN THE 15 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT, ) COURT OF 16 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 17 JOCQUETTA ANN CROSSETT, DECEASED ) ) 18 V. ) DALLAS COUNTY, ) TEXAS 19 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 20 PSYCHIATRIC COMPANY, INC. ) D/B/A/ HCA WILLOW PARK ) 101ST JUDICIAL 21 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D. ) Page 2 1 * * * * * * * * * * 2 NO. A-921,405-C 3 MARIA GUADALUPE REVES ) IN THE 4 INDIVIDUALLY AND AS NEXT ) DISTRICT COURT FRIEND OF GRANT JULIAN REVES ) OF 5 A MINOR CHILD, AND ON BEHALF ) OF THE ESTATE OF CHRISTIAN ) 6 MARIE REVES, DECEASED ) ) ORANGE COUNTY, 7 V. ) TEXAS ) 8 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, RAVIKUMAR ) 9 KANNEGANTI, M.D., HOSPITAL ) CORPORATION OF AMERICA, A ) 10 TENNESSEE CORPORATION, HEALTH ) SERVICES ACQUISITION CORP., ) 11 A DELAWARE CORPORATION, ) HCA PSYCHIATRIC COMPANY, A ) 12 DELAWARE CORPORATION, TEXAS ) PSYCHIATRIC CO., INC.. A/K/A ) 13 AND/OR D/B/A HCA BEAUMONT ) NEUROLOGICAL HOSPITAL, AND HCA ) 14 HEALTH SERVICES OF TEXAS, INC. ) 128TH JUDICIAL A/K/A AND/OR BEAUMONT ) DISTRICT 15 NEUROLOGICAL HOSPITAL ) Page 3 1 * * * * * * * * * * 2 3 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS COUNTY DEPARTMENT - LAW DIVISION 4 RENATO DI SILVESTRO, Individually ) 5 and as Special Administrator of ) the Estate of JOHN DI SILVESTRO, ) 6 Deceased, ) ) 7 Plaintiff, ) ) 8 v. ) No. 91 L 7881 ) 9 ROBERT L. NELSON, et al., ) ) 10 Defendants, ) ) 11 GEORGE MELNICK, M.D. and PETER ) FINK, M.D. ) 12 ) Respondents in Discovery.) 13 * * * * * * * * * * Page 4 1 2 SUPERIOR COURT OF THE STATE OF CALIFORNIA 3 FOR THE COUNTY OF LOS ANGELES 4 DR. MARIUS SAINES, etc., et al., ) Case No: ) SC 008331 5 Plaintiffs, ) ) 6 vs. ) ) 7 ELI LILLY & COMPANY, a corporation; ) DISTA PRODUCTS COMPANY, a division ) 8 of Eli Lilly & Company; and DOBS 1- ) 100, inclusive, ) 9 ) Defendants. ) 10 ____________________________________) 11 * * * * * * * * * * 12 NO. 93-8792-D 13 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT 14 ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF INDIVIDUALLY AND AS SURVIVORS ) 15 AND STATUTORY BENEFICIARIES ) OF MAY YUN KUNG, DECEASED ) 16 ) VS. ) DALLAS, COUNTY 17 ) T E X A S ELI LILLY AND COMPANY, DISTA ) 18 PRODUCTS COMPANY, AND MONIQUE ) KUNKLE, PH.D. ) Page 5 1 * * * * * * * * * * 2 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS 3 CIVIL COURT DEPARTMENT 4 EUGENE HUSLIG, AS ADMINISTRATOR ) 5 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 6 HUSLIG, DECEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 7 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 8 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 9 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 10 ) 94 C 192 PLAINTIFFS, ) 11 VS. ) COURT NO. 7 ) CHAPTER 60 12 MARY L. BILLINGSLEY, EXECUTOR OF ) THE ESTATE OF THAD BILLINGSLEY, ) 13 M.D., DECEASED D/B/A THE BENESSERE ) CENTER, SUSAN C. JOHNSON, PH.D., ) 14 BILLINGSLEY ENTERPRISES, INC., ) F/K/A THAD H. BILLINGSLEY, M.D. ) 15 CHARTERED, D/B/A THE BENESSERE ) CENTER, ELI LILLY AND COMPANY, ) 16 AND DISTA PRODUCTS COMPANY, ) ) 17 DEFENDANTS. ) 18 * * * * * * * * * * Page 6 1 * * * * * * * * * * 2 CAUSE NO. 93-04911-A 3 LINDA JILL WELCH, CARLINDA 4 WELCH REX, CONNAN ROSS WELCH AND CHAD MICHAEL WELCH, 5 INDIVIDUALLY AND AS SURVIVORS AND STATUTORY BENEFICIARIES 6 OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 7 V. 8 ELI LILLY AND COMPANY, DISTA PRODUCTS COMPANY, NOE NEAVES, 9 M.D., AND MINITH-MEIER CLINIC, P.A. DEFENDANTS Page 7 1 THE DEPOSITION OF DR. ROBERT ZERBE TAKEN AT 2 THE UNIVERSITY HOTEL, ANN ARBOR, MICHIGAN, ON MAY 3 13, 1994; SAID DEPOSITION TAKEN PURSUANT TO 4 NOTICE IN ACCORDANCE WITH THE RULES OF CIVIL 5 PROCEDURE. 6 * * * * * * * * * * 7 A P P E A R A N C E S 8 9 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 10 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 11 PAUL SMITH 12 COUNSEL FOR PLAINTIFFS 745 CAMPBELL CENTER 2 13 8115 NORTH CENTRAL EXPRESSWAY DALLAS, TEXAS 75206 14 LAWRENCE J. MYERS 15 COUNSEL FOR ELI LILLY AND COMPANY AND DEPONENT FREEMAN & HAWKINS 16 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 17 ATLANTA, GEORGIA 30308-3243 18 MARGARET M. HUFF ELI LILLY AND COMPANY 19 LILLY CORPORATE CENTER INDIANAPOLIS, INDIANA 46285 20 LISA GOLDMAN 21 COUNSEL FOR ELI LILLY AND COMPANY MCCARTER & ENGLISH 22 FOUR GATEWAY CENTER 100 MULBERRY STREET 23 NEWARK, NEW JERSEY 07102-4096 Page 8 1 ELIZABETH SMITH COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 2 FRIEND & ASSOCIATES LLP 1301 MCKINNEY #2900 3 HOUSTON, TEXAS 77010 4 BARTON BROWN COUNSEL FOR DR. BILLINGSLEY 5 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 10111 W. 87TH ST. 6 P.O. BOX 12290 OVERLAND PARK, KANSAS 66282 7 ROBERT L. HARRIS 8 COUNSEL FOR NOE NEAVES, M.D. SIFFOLD & ANDERSON, LLP 9 6300 NATIONS BANK PLAZA 901 MAIN STREET 10 DALLAS, TEXAS 75202 11 WILLIAM J. DOWNEY, III COUNSEL FOR PLAINTIFF SAINES 12 KANANACK, MURGATROYD, BAUM & HEDLUND 12100 WILSHIRE BOULEVARD, SUITE 650 13 LOS ANGELES, CALIFORNIA 60025 14 KATHERINE L. LAWS COUNSEL FOR DRS. WITSCHY AND KANNEGANTI 15 BAILEY AND WILLIAMS 3500 NCNB PLAZA 16 901 MAIN STREET DALLAS, TEXAS 75202-3714 Page 9 1 I N D E X 2 3 DEPOSITION OF DR. ROBERT ZERBE 4 5 DIRECT EXAMINATION BY MS. ZETTLER 12 6 DIRECT EXAMINATION BY MR. SMITH 225 7 8 CERTIFIED QUESTION 20 9 10 CERTIFICATE 283 11 ERRATA 284 12 EXHIBITS 13 PLAINTIFFS' EXHIBIT NO. 1 63 PLAINTIFFS' EXHIBIT NO. 2 85 14 PLAINTIFFS' EXHIBIT NO. 3 94 PLAINTIFFS' EXHIBIT NO. 4 133 15 PLAINTIFFS' EXHIBIT NO. 5 163 PLAINTIFFS' EXHIBIT NO. 6 171 16 PLAINTIFFS' EXHIBIT NO. 7 183 PLAINTIFFS' EXHIBIT NO. 8 186 17 PLAINTIFFS' EXHIBIT NO. 9 192 PLAINTIFFS' EXHIBIT NO. 10 221 Page 10 1 COMES DR. ROBERT L. ZERBE, CALLED 2 BY THE PLAINTIFFS, AND AFTER FIRST BEING DULY 3 SWORN, WAS DEPOSED AND TESTIFIED AS FOLLOWS: 4 * * * * * * * * * * 5 MR. MYERS: Nancy, before we start, 6 just so we can make a record of this, this 7 deposition, as was the deposition of Mister Wood 8 yesterday, is being taken in a number of cases 9 for which notices have been issued, and in 10 particular with respect to Mister Paul Smith's 11 notices in the Biffle, Welch, Kung, Crossett, 12 Reves and Huslig cases, we have an agreement that 13 the multi-district confidentiality order shall 14 control the deposition and any use of documents 15 in the deposition. Is that right, Mister Smith? 16 MR. SMITH: What I don't understand is 17 how you can spit off the names of my cases so 18 fast. 19 MR. MYERS: It's like telephone 20 numbers. 21 MR. SMITH: I can't even do that, and 22 they're my clients. 23 MR. MYERS: It's like telephone 24 numbers, I can remember them pretty well. Page 11 1 MR. SMITH: We're agreeable. 2 MR. MYERS: Thank you very much. 3 MS. ZETTLER: Also, the deps have been 4 noticed in my Di Silvestro case, and I believe in 5 the Gardner case, and if it wasn't noticed in 6 Gardner, we have the same agreement that we had 7 yesterday, that the depo will be applicable to 8 that case. 9 MR. MYERS: Right, it's the same 10 agreement. 11 MS. LAWS: And we have all the same 12 agreements with respect to objections -- 13 MR. MYERS: Yes. 14 * * * * * * * * * * 15 DIRECT EXAMINATION 16 BY MS. ZETTLER: 17 Q. Could you state your full name 18 for the record, Doctor? 19 A. Robert Lowell Zerbe. 20 MS. ZETTLER: Let the record reflect 21 that this is the discovery and evidence 22 deposition of Doctor Zerbe, taken pursuant to 23 various notices and rules of various courts. 24 Q. Doctor Zerbe, have you given a Page 12 1 deposition before? 2 A. Yes. 3 Q. How many times have you been 4 deposed? 5 A. Twice. 6 Q. Were both of those cases or 7 times related to your work with Eli Lilly? 8 A. Yes. 9 Q. Were they both related to your 10 work on Prozac? 11 A. No. 12 Q. Were either of them related to 13 your work on Prozac? 14 A. Yes. 15 Q. Tell me about the deposition 16 that you gave related to your work on Prozac, 17 when did it occur? 18 A. I'm not sure of the exact 19 date. 20 Q. Give me your best estimate. 21 A. Approximately two years ago. 22 Q. Where was that deposition 23 held? 24 A. In Los Angeles. Page 13 1 Q. How long did the deposition 2 last? 3 A. One day. 4 Q. Was the deposition given in 5 relationship to a lawsuit, if you know? 6 A. I believe it was. 7 Q. Do you know what the name of 8 that lawsuit was? 9 A. I don't remember the case. 10 Q. Was it a suit involving an 11 injured plaintiff, injured person? 12 A. I believe that was the nature 13 of it, yes. 14 Q. Were you being deposed as an 15 expert witness in this case, if you know? 16 A. I'm not sure how you're 17 defining expert witness. 18 Q. Were you asked by Lilly to 19 testify potentially at the trial of that case as 20 an expert witness to give opinion testimony 21 related to your work on Prozac or any other 22 psychiatric work you've done? 23 A. Yes. 24 Q. Has that case been tried to Page 14 1 your knowledge? 2 A. No. 3 Q. Have you been asked to testify 4 as an expert witness in any other Prozac case? 5 A. No. 6 Q. Are you familiar with Joseph 7 Wesbecker? 8 A. I'm not familiar with him, but 9 I'm familiar with the case or the situation, yes. 10 Q. Have you been told or asked by 11 anybody at Lilly or anywhere else to testify at 12 the trial of that case if it goes to trial? 13 A. I have not been asked to 14 testify anyplace. 15 Q. Did you bring any documents 16 with you today, Doctor? 17 A. No, I didn't. 18 Q. Do you retain any documents 19 related to your work on Fluoxetine presently? 20 A. No. 21 Q. When did you leave Eli Lilly? 22 A. July of 1993. 23 Q. Was that to come to your 24 present position? Page 15 1 A. Yes. 2 Q. And what is your present 3 position? 4 A. I'm senior vice-president for 5 clinical research at Park Davis. 6 Q. Have you been with Park Davis 7 continuously since July of '93? 8 A. Yes. 9 Q. In the same position? 10 A. Yes. 11 Q. What did you do to prepare for 12 your deposition today? 13 A. I had two meetings with the 14 lawyers representing Lilly. 15 Q. Okay. When did that first 16 meeting occur? 17 A. I'm not sure of the exact 18 date. 19 Q. Can you give me a year? 20 A. It was this year. 21 Q. Okay. Do you remember what 22 month? 23 A. It was April -- well, I'm not 24 sure, it was April or May. Page 16 1 Q. Spring? 2 A. Spring, yes. 3 Q. So Spring of '93? 4 A. Spring of '93, yes. 5 Q. Was it before you left Lilly? 6 A. No, no, I'm sorry, it's Spring 7 of '94, it's this Spring, yes. 8 Q. Okay. I keep forgetting it's 9 already May. 10 A. Spring of '94, I'm sorry. 11 Q. No, I apologize, it's been a 12 long week. When you're over thirty, you tend to 13 make time slow down. Where did you meet with 14 lawyers representing Lilly in the Spring of this 15 year? 16 A. The first meeting was held at 17 Lilly in Indianapolis. 18 Q. And just to make this clear, 19 when you met with Lilly at Lilly in the Spring of 20 '94, you were no longer employed by Lilly, 21 correct? 22 A. That's correct. 23 Q. Who did you meet with? 24 A. I don't know the names of all Page 17 1 the people, to be honest with you, they were the 2 lawyers representing Lilly. 3 Q. How many lawyers were there 4 approximately? 5 A. Two or -- three. 6 Q. Anybody who's sitting at the 7 table here, were they there, like Larry Myers or 8 Mary? 9 A. No. 10 Q. Were they lawyers that -- 11 in-house lawyers for Lilly? 12 A. One was an in-house lawyer for 13 Lilly. 14 Q. Male or female? 15 A. Male. 16 Q. Okay. Curt Oltman? 17 A. I believe it was Curt, I 18 couldn't be absolutely certain, but I believe 19 that was Curt. 20 Q. The other two lawyers, were 21 they men or women? 22 A. Men. 23 Q. And the second time you met 24 with Lilly lawyers, when was that? Page 18 1 A. Yesterday. 2 Q. Who did you meet with 3 yesterday? 4 A. Mary Huff was there as well as 5 Steve, but I don't remember Steve's last name. 6 Q. Steve Lore? 7 A. I don't remember. 8 MR. MYERS: Yes. 9 Q. And where did you meet? 10 A. We met here in Ann Arbor. 11 MR. SMITH: Where is he? 12 MR. MYERS: We're holding him in 13 reserve. 14 Q. How long was the meeting 15 yesterday with Mary and Steve? 16 A. About four hours. 17 Q. What time did that happen? 18 A. Yesterday afternoon. 19 Q. Let's talk about the first 20 meeting you had at Lilly in the Spring of this 21 year. What did you discuss during that meeting? 22 MR. MYERS: Hold on. Let me object to 23 the question and advise you, Doctor Zerbe, and 24 instruct you that you're not required to disclose Page 19 1 that information, and to tell you, Ms. Zettler, 2 that for purposes of this deposition I'm 3 representing Doctor Zerbe and Eli Lilly and 4 Company in that the matters that he's going to be 5 examined about relate to his employment with 6 Lilly, and thus those matters are privileged and 7 he's not going to disclose that information. 8 MS. ZETTLER: Larry, there's no 9 privilege here, and you know it, so are you going 10 to make me call the judge right now? 11 MR. MYERS: You can do whatever you 12 like, but we're not going to disclose the 13 substance of those communications. 14 MR. SMITH: Certify the question, and 15 I'll call the judge at the first break. 16 (QUESTION CERTIFIED.). 17 Q. (BY MS. ZETTLER) Doctor, just 18 so you know, Mister Myers is not completely 19 accurate in what he's just told you. There is no 20 privilege because you no longer work for Eli 21 Lilly and Company. What we are going to do at 22 the break is call the judge and get a ruling from 23 him and ask him to require that you answer the 24 question. Same thing at the meeting yesterday, Page 20 1 what did you discuss with Mary Huff and Steve 2 Lore? 3 MR. MYERS: Excuse me, same direction 4 and same direction not to answer the question. 5 Q. Are you paying Mister Myers to 6 represent you in this case? 7 A. No. 8 Q. Are you -- do you have a 9 lawyer? 10 A. Only -- not in this matter. 11 Q. Do you have a personal lawyer 12 that handles your affairs generally? 13 A. Yes. 14 Q. Did you ask that lawyer to 15 represent you today during the deposition? 16 A. No. 17 Q. Were you advised by Mister 18 Myers or anybody else on behalf of Lilly that you 19 could retain your own lawyer to come to this 20 deposition to represent you? 21 A. I think I have been informed 22 of that possibility. 23 Q. Why did you leave Eli Lilly? 24 A. I just had a better Page 21 1 opportunity. 2 Q. What was your position with 3 Lilly when you left? 4 A. I was vice-president in charge 5 of world wide regulatory affairs. 6 Q. What was it about your 7 opportunity with your current employer that was 8 better than your job at Lilly? 9 A. More responsibility, more 10 independence, better pay, more of what I wanted 11 to do. 12 Q. When you say more 13 responsibility than your job at Lilly, what do 14 you mean? 15 A. Well, more people in terms of 16 the department -- more direct responsibility with 17 designing clinical trials and so forth. 18 Q. How about when you said more 19 independence, what do you mean by that? 20 A. Well, it's a smaller 21 organization so there's more opportunity to set 22 your own direction. 23 Q. Did anybody from Lilly try to 24 persuade you not to leave the company? Page 22 1 A. I think people were trying to 2 encourage me to stay, I mean, but nothing other 3 than, you know, verbal encouragement. 4 Q. Who encouraged you to stay? 5 A. I had various conversations 6 with various people, and I suppose they all 7 encouraged me to stay. 8 Q. Can you give me some examples? 9 A. Well, Doctor Perelman, Gus 10 Wantanabe, Leigh Thompson. 11 Q. What did Doctor Thompson say 12 to try to get you to stay at Lilly? 13 A. Oh, there weren't specific 14 comments, you know, it was just the the usual 15 hate to see you leave. 16 Q. But they didn't go as far as 17 to offer you a position with more responsibility 18 or more money? 19 A. No. 20 Q. Did that surprise you? 21 A. Not really, no. 22 Q. How long had you been with 23 Lilly at the time you left? 24 A. Eleven years. Page 23 1 Q. Does Parke Davis market a 2 selective seratonin reuptake inhibitor? 3 A. No. 4 Q. Did you sign any kind of 5 non-competition agreement with Lilly or anything 6 like that when you left? 7 A. No. 8 Q. Did you review any documents 9 in preparation for your deposition? 10 A. By review documents, what do 11 you mean? 12 Q. Did you look at any documents 13 before today's deposition in preparation for the 14 deposition? 15 A. No. 16 Q. Did you ask anybody to see 17 documents to review? 18 A. No. 19 Q. Did anybody offer to show you 20 documents to review in preparation for your 21 deposition today? 22 A. No. 23 Q. When did you first start at 24 Lilly? Page 24 1 A. June, 1982. 2 Q. Did you work continually for 3 Lilly from June 1982 until July 1993? 4 A. Yes. 5 Q. Why don't you give us a little 6 bit of background with regards to your education 7 after high school. 8 A. I attended undergraduate 9 school at Indiana University, medical school at 10 Indiana University, did internship, residency and 11 fellowship at Indiana, and then spent two years 12 at the National Institutes of Health prior to 13 joining Lilly. 14 Q. Was your two years at the 15 National Institutes of Health like a residency or 16 anything like that? 17 A. It was a research fellowship. 18 Q. How did you get that job? 19 A. I applied for it, contacted 20 the person responsible for the laboratory there 21 and was invited to come. 22 Q. What did you do with NIH? 23 A. I was a senior staff fellow. 24 Q. What did your responsibilities Page 25 1 as a senior staff fellow entail? 2 A. It was really all research, I 3 didn't have any people responsibilities, it was 4 all research projects. 5 Q. Did you do any research 6 related to psychotropic drugs? 7 A. No. 8 Q. Did you do any research 9 related to psychiatry in any way, or psychology? 10 A. Really only loosely related to 11 psychiatry. 12 Q. Why don't you give me an 13 example. 14 A. Well, we were studying a 15 hormone in the brain, so it was neuro endocrine 16 studies. There was some speculation this hormone 17 may be related to things like memory and so 18 forth, but that's the extent of that linkage to 19 psychotropic studies. 20 Q. What hormone? 21 A. Vasopressin. 22 Q. Did you use your experience 23 and research in vasopressin in any way in your 24 job at Eli Lilly? Page 26 1 A. Only on rare occasions. 2 Q. How about related to Prozac? 3 A. Again, relatively few 4 situations. 5 Q. Okay. Can you give me an 6 example of one of those situations? 7 A. There was a concern about 8 hyponatremia early on, and vasopressin is the 9 antidiuretic hormone, and so I was asked to 10 evaluate the information on hyponatremia, and we 11 in fact designed some studies to address that 12 question. 13 Q. Any other way that your work 14 with vasopressin was used in your job at Lilly 15 related to Prozac? 16 A. Not that I recall. 17 Q. Are you Board certified in any 18 specialty in medicine? 19 A. Internal medicine. 20 Q. Are you now or have you ever 21 been a psychiatrist? 22 A. No. 23 Q. Have you ever had an interest 24 in psychiatry other than your work on Prozac? Page 27 1 A. Other than the usual interest 2 in all aspects of medicine, no. 3 Q. Have you -- did you do a 4 residency in psychiatry or internship in 5 psychiatry during your medical school years? 6 A. No. 7 Q. Have you ever practiced 8 psychiatry? 9 A. No. 10 Q. When did you become Board 11 certified in internal medicine? 12 A. Let's see, it would have been 13 approximately 1979, approximately. 14 Q. Have you ever prescribed 15 Prozac? 16 A. No. 17 Q. How did you come to work at 18 Lilly? 19 A. I was asked by a former 20 associate to come and consider a job. 21 Q. Former associate of yours? 22 A. Yes. 23 Q. Who? 24 A. David Henry. Page 28 1 Q. When you say a former 2 associate, what do you mean? 3 A. He and I had worked on some 4 research projects when I was at Indiana. 5 Q. Is David Henry a doctor -- 6 A. Yes. 7 Q. -- clinical doctor? What was 8 Doctor Henry's position with Lilly at the time 9 that he asked you to come work there? 10 A. I don't know what his formal 11 title was at that time. 12 Q. Can you give me an idea of 13 what area he worked in? 14 A. He was working in clinical 15 pharmacology at the Lilly clinic. 16 Q. Do you know what type of drugs 17 he was working on? 18 A. I don't recall specifically. 19 Everybody at the clinic had responsibilities for 20 different types of drugs. 21 Q. Okay. What was your first 22 position with Lilly? 23 A. I was -- I'm not sure, I don't 24 remember the exact title, but I was an associate Page 29 1 clinical pharmacologist or something like that. 2 Q. How long were you an associate 3 clinical pharmacologist? 4 A. From June of 1982 until 5 approximately October of 1983. 6 Q. Okay. And what was your next 7 position with Lilly? 8 A. I was a director of the neuro 9 endocrine division. 10 Q. How long were you director of 11 the neuro endocrine division? 12 A. From October of '83 until 13 approximately June of '85. 14 Q. What was your next position? 15 A. I was the director for 16 clinical investigation in Europe. 17 Q. How long were you the director 18 for clinical investigation in Europe? 19 A. From approximately July of 20 1985 until approximately May of '87. 21 Q. Did you live over in Europe 22 during that period of time? 23 A. Yes. 24 Q. Where did you live? Page 30 1 A. I lived in Camberly in Surrey, 2 in England. 3 Q. Which affiliate did you work 4 out of? 5 A. It wasn't really an affiliate, 6 it was the Lilly research center. 7 Q. Where is that? 8 A. It's in Windelsham. 9 Q. I've seen some documents where 10 it indicates that you were working out of Erl 11 Wood. Did you ever work out of Erl Wood? 12 A. Yes, that's the Lilly research 13 center. 14 Q. So the Wendelsham research 15 center is known commonly at Lilly as Erl Wood? 16 A. Yes. 17 Q. Were you at Erl Wood from 18 approximately July of '85 to approximately May of 19 '87? 20 A. I was at Erl Wood beyond that 21 time as well. 22 Q. How long were you at Erl Wood? 23 A. Until approximately March of 24 '89. Page 31 1 Q. Did you come back to the 2 states at all for any extended period of time 3 during that period that you worked out of Erl 4 Wood other than vacations and holidays and things 5 like that? 6 A. I'm not sure what you mean by 7 an extended period of time. 8 Q. Would you come back for like a 9 month or so to work out of the Indy office? 10 A. No. 11 Q. After your position as 12 director for clinical investigations in Europe, 13 what was your next position at Lilly? 14 A. I was the managing director at 15 Erl Wood. 16 Q. How long were you the managing 17 direct at Erl Wood? 18 A. From -- again, I don't want to 19 confuse you on the dates. From the time I left 20 the job as director of clinical investigation 21 until I returned to the U.S. in March of 1989. 22 Q. Okay. So approximately May of 23 '87 to March of '89? 24 A. That's approximately right. Page 32 1 Q. Okay. What was your next 2 position? 3 A. I was executive director for 4 clinical investigation and regulatory affairs. 5 Q. Executive director for 6 clinical investigation and regulatory affairs? 7 A. Something like that. 8 Q. How long were you in that 9 position? 10 A. Well, I guess that title -- 11 until I was promoted to vice-president, which 12 was, I guess, something like July of 1991, I 13 think. 14 Q. When you say that title, did 15 your responsibilities change during that period 16 of time in that position? 17 A. There were various changes in 18 responsibilities, but my title never changed. 19 Q. Okay. Then you became 20 vice-president of what? 21 A. It's Lilly Research 22 Laboratories. 23 Q. And that was in July of '91? 24 A. Yes. Page 33 1 Q. How long were you in that 2 position? 3 A. Until I left. 4 Q. For two years, until July of 5 '93? 6 A. That's right. 7 Q. When did you first start 8 working with Fluoxetine? 9 A. In approximately November of 10 1983. 11 Q. After you had been sent over 12 to Europe? 13 A. No. 14 Q. Oh, I'm sorry. What were your 15 first responsibilities with regards to Prozac or 16 fluoxetine hydrochloride? 17 A. I was responsible for the 18 division, the neuro endocrine division, and that 19 division was responsible for Prozac. 20 Q. Is the neuro endocrine 21 division different than the medical division? 22 A. Yes. 23 Q. Okay. What are the 24 differences between the responsibilities for the Page 34 1 neuro endocrine division and the medical 2 division? 3 A. Well, the formal title medical 4 division, I'm not sure that there's actually a 5 formal organizational structure called the 6 medical division, but the neuro endocrine 7 division is one of the specialty areas within the 8 larger medical group. 9 Q. Was there a CNS division? 10 A. The central nervous system 11 products were within the neuro endocrine 12 division. 13 Q. So you were in charge of the 14 division that at that time was responsible for 15 developing and testing Prozac -- 16 A. We had -- 17 Q. -- clinical trials, animal 18 studies, things of that nature? 19 A. No animal studies, only the 20 clinical trials done by investigators outside of 21 the company. 22 Q. Okay. How about healthy 23 volunteer studies done at the clinics? 24 A. No, I was not responsible for Page 35 1 that at that time. 2 Q. When you became responsible 3 for the neuro endocrine division, how much of 4 your responsibility as director of that division 5 entailed Prozac as opposed to other compounds? 6 A. I'm sorry, could you repeat 7 the question? 8 Q. Sure. I'm trying to get an 9 idea of how much of your time was spent working 10 on Prozac as of November of '83. 11 A. I don't know, it would be an 12 approximation, maybe twenty-five percent. 13 Q. Did there ever come a time 14 when all of your responsibilities were directly 15 related to Prozac and you weren't working on any 16 other compounds? 17 A. No. 18 Q. What was the -- 19 A. Not that I recall. 20 Q. What was the largest 21 percentage of time at any given time that you 22 worked on Prozac as opposed to other compounds? 23 A. It would be purely 24 speculative. Page 36 1 MR. MYERS: If you can give a 2 reasonable estimate, Doctor, do it, but don't 3 speculate or guess, but if you can give a 4 reasonable ballpark estimate, go ahead. 5 A. Can you repeat the question 6 because I'm not sure, I want to make sure I'm 7 answering the right question. 8 Q. I want to know if there was 9 ever a time when the majority of your time was 10 spent working on Prozac as opposed to other 11 compounds? 12 A. Yes, there was a time that the 13 majority of my time was spent working on Prozac. 14 Q. When was that period of time? 15 A. I would say 1990, '91. 16 Q. Okay. So approximately a year 17 within 1990, '91? 18 A. Something like that. 19 Q. And that was when you were 20 executive director of clinical investigations? 21 A. Right. 22 Q. Was that the period of time 23 between when Doctor Teicher's article came out 24 and the 1991 drug advisory committee meeting? Page 37 1 A. Yes. 2 Q. How much of your time did you 3 spend on Prozac during that period of time? 4 A. Again, purely speculation, 5 probably somewhat over fifty percent of my time. 6 Q. Do you know anybody else from 7 the National Institutes of Health that has come 8 to work for Lilly? 9 A. You mean before or after I 10 came? 11 Q. Either. 12 A. Well, Doctor Henry had been at 13 the National Institutes of Health. 14 Q. Okay. 15 A. Doctor Wantanabe was at the 16 National Institutes of Health. 17 Q. Anybody else? 18 A. Steve Paul, who's come since 19 then, was at the National Institutes of Health. 20 Q. Is there an interrelationship 21 between the National Institutes of Health and the 22 National Institute of Mental Health? 23 A. Yes. Technically, I 24 simplified it, I actually worked for the National Page 38 1 Institute of Mental Health, as did, I think, all 2 of those people I named. But it's all in the 3 same -- on the same campus, even in the same 4 building. 5 Q. Did the National Institute of 6 Mental Health come under the purview of the 7 National Institutes of Health or are they two 8 separate entities? 9 A. I don't know technically how 10 they're organized, but in general, I mean, it's 11 fair to say it's kind of the same campus, the 12 same facility. 13 Q. Prior to coming to work at 14 Lilly as an employee, had you ever done any work 15 for Lilly or on behalf of Lilly? 16 A. No, I had never done any 17 clinical trials for Lilly. 18 Q. Any work whatsoever? 19 A. The only work was the work 20 that I mentioned with Doctor Henry, that we 21 measured some hormones and so forth in some of 22 the studies that he had done at the Lilly clinic, 23 but I was not paid anything for that. 24 Q. Doctor Henry had done studies Page 39 1 at the Lilly clinic on behalf of Lilly? 2 A. Doctor Henry was a Lilly 3 employee. 4 Q. So at the time you worked with 5 him indirectly on the hormone studies, he was an 6 employee at Lilly. 7 A. Yes. 8 Q. Give me an idea of what your 9 responsibilities were with regards to Prozac when 10 you were the director of the neuro endocrine 11 division, other than your general supervisory -- 12 did you have any direct responsibility with 13 regards to Prozac during that period of time? 14 A. Other than the general 15 responsibility, no. 16 Q. Can you tell me the names of 17 some of the people that worked under you directly 18 on Prozac during that period of time? 19 A. Paul Stark. 20 Q. Anybody else? 21 A. Paul Stark was the primary 22 person. 23 Q. He was the medical monitor 24 during that period of time on Prozac? Page 40 1 A. Yes. 2 Q. Did you ever work with I. H. 3 Slater? 4 A. No. 5 Q. Do you know Doctor Slater? 6 A. No. 7 Q. Do you know of Doctor Slater? 8 A. I know of Doctor Slater. 9 Q. Tell me what you know about 10 Doctor Slater. 11 A. Really very little other than 12 I think he was responsible for some of the very 13 early studies. 14 Q. Do you ever talk with Doctor 15 Stark about Doctor Slater? 16 A. No, I don't ever recall 17 talking to him about Doctor Slater. 18 Q. What was -- Doctor Stark was 19 medical monitor on Prozac. Did he have any other 20 responsibilities during that period of time? 21 A. My recollection was that was 22 his sole responsibility, Prozac. 23 Q. How long did you work in that 24 capacity as director of the neuro endocrine Page 41 1 division with responsibilities for Prozac, was 2 that the entire time you were in that division? 3 A. Yes. 4 Q. Then in your next capacity as 5 director of clinical investigations in Europe, 6 did you have any responsibilities with regards to 7 Prozac? 8 A. There were European programs 9 with Prozac as well, and that was part of my 10 responsibility, really more to coordinate that 11 than to actually drive the -- do the studies. 12 Q. Did you have any 13 responsibilities with regards to trying to get 14 Prozac registered in other countries? 15 A. By other countries, what 16 countries do you mean? 17 Q. Outside the U.S. 18 A. Outside the U.S. I was 19 involved in -- yes, I was. 20 Q. Any countries in particular 21 during the period of time that you worked in that 22 capacity? 23 A. I can't remember exactly at 24 what point we met with various regulators, Page 42 1 whether it was within that capacity or some other 2 capacity, but I was involved from time to time in 3 a number of countries in Europe. 4 Q. Did you personally meet with 5 regulators in other countries? 6 A. Occasionally. 7 Q. Which countries? 8 A. I, again, don't remember the 9 specifics, but we met with regulatory authorities 10 in the UK, in France, and Finland. 11 Q. How about Germany? 12 A. I don't recall ever meeting 13 with the regulators in Germany. 14 MR. SMITH: Let the record reflect 15 that Mister Bill Downey has entered the room, 16 much to the disappointment of everybody here. 17 MR. MYERS: All around the table. 18 MR. SMITH: Including plaintiffs' 19 counsel. 20 MR. DOWNEY: You changed it all on me, 21 but I still found you. 22 Q. Do you recall there being any 23 problems or any issues that arose that either 24 prevented or delayed the registration of Prozac Page 43 1 in the UK, France or Finland when you were 2 working on registration in those countries? 3 A. There were, you know, a 4 variety of issues as always arise with 5 applications. 6 Q. Can you give me some examples? 7 A. I really don't recall which 8 issues, you know, for any specific country. 9 Q. How about any issues that 10 prevented the drug being registered or greatly 11 delayed the registration of the drug in any of 12 these countries? 13 A. There were some additional 14 studies that the French wanted and the Germans 15 wanted. 16 Q. To demonstrate what? 17 A. There were very specific 18 things. The French wanted a study in 19 melancholia, and the Germans wanted in-patient 20 studies. 21 Q. Why did the Germans want an 22 in-patient study or in-patient studies? 23 A. They felt that the in-patients 24 were more severely depressed, but there really Page 44 1 wasn't data to support that. We ended up doing 2 the studies, but there was really no evidence 3 that that was true, that the patients were any 4 more severely depressed simply because they were 5 hospitalized. 6 Q. How many studies did you do in 7 response to the question by the German government 8 about in-patients? 9 A. Specifically in response to 10 the German government? 11 Q. Sure. 12 A. I believe, I'm not certain, 13 there are others that could probably answer the 14 question better, but my recollection is there was 15 one study done in Germany to address that 16 question. 17 Q. What was the name of the 18 study? 19 A. I don't recall the name of the 20 study. 21 Q. Do you know who conducted the 22 study, was it done in Germany? 23 A. It was done in Germany, yes, 24 but I don't recall the name of the investigator. Page 45 1 Q. Do you know if the results of 2 that study have been published either here or in 3 Europe? 4 A. I don't know if the results 5 have been studied -- I'm sorry, I don't know that 6 the results have been published. 7 Q. Do you know that they haven't 8 been published? 9 A. I don't know that they haven't 10 been published either. 11 Q. Do you know if the final 12 report of that study was submitted to the FDA? 13 A. I can't personally verify it, 14 but that would be our standard procedure to 15 submit it to the FDA, so I assume that it was 16 submitted. 17 Q. Any other questions raised by 18 the German government with regards to Prozac? 19 A. Specifically at the time of 20 the in-patient study? 21 Q. No, anytime that you're aware 22 of. 23 A. Well, the Germans early on had 24 questions about suicidality. Page 46 1 Q. When you say early on, what 2 time frame are we talking about? 3 A. Approximately 1986. 4 Q. Was it before or after you 5 became director for clinical investigations in 6 Europe? 7 A. It was around that same time. 8 I don't know whether it was before or after, but 9 it was around that same time. 10 Q. What questions about 11 suicidality did they raise? 12 A. They were concerned about the 13 possibility of activation with Prozac. 14 Q. When you say activation, what 15 do you mean? 16 A. Well, I mean I think they're 17 probably better able to describe what they meant 18 exactly, but the concern was that Prozac was a 19 non-sedating antidepressant, and that in their 20 minds, therefore, it was activating. 21 Q. Did they ask you to do any 22 studies with regards to the question of 23 suicidality and the use of Prozac? 24 A. I can't recall exactly what Page 47 1 they asked for, but we did go back and look very 2 carefully at the data base in response to those 3 questions, and -- well -- 4 Q. What data base? 5 A. The data base that existed at 6 that time, you know, that Lilly had from clinical 7 trials. 8 Q. Clinical trial data base, in 9 other words the results of the various clinical 10 trials that had been conducted up until that 11 period of time? 12 A. That's correct. 13 Q. Did that data base, to your 14 knowledge, include clinical trials that were 15 conducted in the United States as well as outside 16 the United States? 17 A. I don't recall exactly which 18 studies, I think most of the studies were studies 19 done in the U.S. 20 Q. To your knowledge was there 21 ever a period of time when there was a separate 22 data base for studies done in the United States 23 and one or more for studies done outside the 24 United States? Page 48 1 A. Well, I'm not sure how to 2 answer that question because there aren't -- it 3 isn't simply one data base, it's really a whole 4 conglomerate of a whole group of data bases which 5 can be pooled in various ways. So the answer is 6 there are a number of subsets of the data base, 7 it's a very loose term. 8 Q. What subsets are there or were 9 there, that you're aware of? 10 A. I mean there are infinite 11 number of subsets, I'm not sure -- if you can try 12 to reword the question. 13 Q. Are you talking about a 14 specific data base set up for every single study 15 that was conducted or was there a data base, for 16 instance, set up that contained information on 17 all double-blind controlled studies as opposed to 18 open-label studies? 19 A. Again, always the data base 20 was used to the optimum, whatever way we could 21 reasonably, scientifically combine data to get a 22 more powerful answer to a question, we would do 23 that. So in some situations one would look at 24 double-blind data, because those could reasonably Page 49 1 be pooled, in other situations that was not 2 scientifically valid to pool those data. 3 Q. What I'm trying to find out, 4 Doctor, is how the computerization of the data 5 from the studies was set up. 6 A. The computerization of the 7 studies, literally every study had a data base. 8 Q. Okay. So you could -- and 9 there were computer files that were opened on 10 each study so you could pool information from 11 each file anyway you needed to? 12 A. You could pool data to, again, 13 combine studies that were similar to give a more 14 powerful answer to a difficult question, if 15 that's what you mean. 16 Q. Okay. I just want to make 17 sure that we're not talking about one data base 18 that contained all information on double-blind 19 controlled studies as opposed to another data 20 base that had all open-label studies and another 21 data base that had compassionate-use studies, 22 things like that. It was more broken down? 23 A. It was not that clearly 24 defined, and certainly not -- well, it was not Page 50 1 that clearly defined. It could be pooled 2 together in a variety of ways. 3 Q. You're saying that in response 4 to the German government's questions about 5 suicidality data was looked at for all studies 6 that had been conducted up to that period of 7 time? 8 A. Yes. That's to my 9 recollection. I was not as closely involved in 10 the actual generation review of those data 11 because I was in Europe and the data base was in 12 the U.S. 13 Q. Do you know how many studies 14 have been conducted on Prozac throughout the 15 world at that time? 16 A. I really don't know, I 17 couldn't give you a figure. 18 Q. Do you know how many studies 19 have to date, or at least until the time you left 20 Lilly, had been conducted on Prozac world wide, 21 on depression? 22 A. A lot. I really don't know 23 the number. 24 Q. Hundreds? Page 51 1 A. I would say hundreds. 2 Q. Besides reviewing the data 3 base, were any other actions taken by Lilly in 4 response to the questions raised by the German 5 government with regards to suicidality? 6 A. Well, the clinical trial data 7 base was reviewed, and those data were shared 8 with outside consultants. 9 Q. Doctor Perelman? 10 A. That name is not the name that 11 I -- that name does not ring a bell. 12 Q. Who? 13 A. Again -- well -- 14 Q. Just to the best of your 15 recollection. 16 A. The best of my recollection, 17 the name that comes to mind is Doctor Winoker. 18 Q. Where was Doctor Winoker 19 located? 20 A. I don't recall. 21 Q. Was he in Europe? 22 A. No. 23 Q. He was here in the United 24 States? Page 52 1 A. That's my recollection, yes. 2 Q. Have you heard of a Doctor 3 Herrmann in connection with the registration 4 efforts in Germany? 5 A. I don't recall Doctor Herrmann 6 at all. 7 Q. Anybody else besides Doctor 8 Winoker that you recall the data base information 9 was submitted to for review? 10 A. Outside individuals? 11 Q. Right. 12 A. No, I don't recall anyone 13 else. But again, I was not the one -- I was not 14 directly responsible for that. 15 Q. Who was directly responsible? 16 A. Doctor Wernicke. 17 Q. Anybody else in either the 18 U.S. or Europe? 19 A. No, I think Doctor Wernicke 20 was the primary person. 21 Q. How about Hans Weber, what was 22 his responsibility? 23 A. Doctor Weber was the medical 24 director in Germany, and he would have shared Page 53 1 responsibility, you're right. 2 Q. Was the German government 3 satisfied with the responses to the questions by 4 Lilly on suicidality? 5 A. Yes. 6 Q. Do you know whether or not 7 Prozac is being marketed in Germany today? 8 A. As best I know, it is, yes. 9 Q. Do you know when it was 10 finally approved for marketing in Germany? 11 A. I don't recall the exact date. 12 Q. Can you give me a year? 13 A. I would say 19 -- well, again, 14 speculation, early '90s. 15 Q. How many times was Lilly's 16 application or petition for approval of marketing 17 of Prozac in Germany submitted? 18 A. I don't really know how many 19 times it was submitted. 20 Q. Okay. When was it first 21 submitted, as far as you remember? 22 A. Well, again, I was not 23 involved directly in that submission, so it would 24 be speculation. Page 54 1 MR. MYERS: Let met tell you, Doctor, 2 as I say, if you can give a reasonable estimate, 3 go ahead, but don't guess or speculate. If you 4 can give a reasonable estimate of the date, give 5 it to Ms. Zettler. 6 A. A reasonable estimate would be 7 within a few years after the filing in the U.S. 8 Q. So '86 or '87? 9 A. That would be a reasonable 10 estimate. 11 Q. Were you aware, Doctor, that 12 Lilly's application for approval of marketing of 13 Prozac in Germany was rejected at least once 14 before it was finally approved? 15 MR. MYERS: I object to the form. You 16 can answer, if you know. 17 MR. SMITH: I object to counsel for 18 Eli Lilly directing a witness who is not an 19 employee of Eli Lilly, who's not been retained by 20 counsel -- who's not been retained by the 21 witness, and directing the witness with respect 22 to how and when and in what manner to answer the 23 question. 24 MR. MYERS: I'm representing the Page 55 1 witness and Lilly for purposes of this 2 deposition, Mister Smith. 3 MS. ZETTLER: Let's take a break and 4 call the judge. 5 (A SHORT RECESS WAS TAKEN.) 6 Q. Doctor Zerbe, how was the 7 issue of suicidality and Prozac raised by the 8 German government? 9 A. I really don't recall the 10 details of how that was done. 11 Q. Do you know if it was raised 12 before or after you went to Europe? 13 A. I believe it was actually 14 before I went to Europe, but it was right around 15 that time, I think, as I said before. 16 Q. Prior to your going to Europe, 17 what responsibilities did you have with regards 18 to clinical investigations, European clinical 19 investigations? 20 A. Well, it was pretty limited. 21 We didn't really have direct responsibility for 22 the European investigations prior to the time 23 that I went to Europe, but we obviously were kept 24 informed of what was going on in Europe, we Page 56 1 worked closely with our European colleagues. 2 Q. Was there somebody who 3 preceded you as director of clinical 4 investigations in Europe? 5 A. No, it was organized 6 differently prior to that. 7 Q. Do you know why you were 8 selected to go to Europe to become director of 9 clinical investigations? 10 A. I think it was career 11 development as much as anything. 12 Q. Before the German government 13 raised the issue of suicidality and the use of 14 Prozac, had anybody else or any other entity 15 raised that issue? 16 A. Not to my knowledge. 17 Q. How about activation and 18 Prozac, did anybody raise that issue? 19 A. I'm sorry, did any -- 20 Q. Any entity or any individual 21 that you recall, prior to the German government 22 raising the issue? 23 A. I don't recall any specific 24 individual or organization that did. Page 57 1 Q. Okay. How do you define 2 activation with regards to Fluoxetine, regardless 3 of whether or not you feel it's activating? 4 A. Well, activation -- I think 5 the perception with regard to Prozac is that 6 activation is the fact that it's non-sedating, 7 specifically, you know, in regards to Prozac, and 8 that's the way I would look at it. 9 Q. Is it your understanding that 10 many other antidepressants that are currently 11 marketed have a sedating effect? 12 A. Most of the antidepressants 13 that were marketed at the time had sedating 14 effects. 15 Q. Okay. In your opinion is 16 Fluoxetine sedating? 17 A. In some individuals, there 18 have been reports of sedation. 19 Q. Okay. Would it be fair to say 20 that in the majority of individuals who take 21 Fluoxetine that is not the case, though? 22 A. Yes, I think that's a fair 23 statement. 24 Q. How about stimulating, in your Page 58 1 opinion is Fluoxetine a stimulating drug? 2 A. Not in my opinion. 3 Q. Why not? 4 A. Well, again, it depends how 5 one would define stimulating, but it's certainly 6 not something that is like amphetamines or 7 anything like that, if that's the implication, 8 Prozac is not, in my opinion, in that category. 9 Q. Do you consider Fluoxetine an 10 activating drug? 11 A. No, I don't -- in my opinion, 12 don't consider it an activating drug, except as I 13 said before in relation to the fact that it is 14 not sedating. 15 Q. Okay. How can it be not 16 sedating and not activating at the same time? 17 A. It has no effect in either 18 stimulation or activation. It improves mood, but 19 doesn't affect either of those. 20 Q. Where do you come to your 21 opinion -- how do you come to your opinion that 22 it's not activating, based on what? 23 A. I base it on the balance of 24 overall evidence, I guess, from the clinical Page 59 1 studies. 2 Q. Anything else besides the 3 clinical studies? 4 A. I think that's the primary set 5 of evidence that I would cite. 6 Q. Okay. If the overall balance 7 of evidence from the clinical studies shows that 8 Fluoxetine is not activating, how did the BGA 9 come to the conclusion that it was? 10 A. Well, I don't know what 11 conclusion the BGA reached or what you're citing 12 specifically. I think, from my perspective, what 13 was being asked at the time is whether it was, 14 what data do you have to address that, the 15 question, and I think in the end, the BGA would 16 have agreed with my statement about the balance 17 of evidence. But I guess that's how I would 18 summarize it. Did that answer your question? 19 Q. Well, maybe, maybe in part. 20 At one point the BGA felt that there was a risk 21 of increased suicidality with Fluoxetine, did it 22 not? 23 A. Well, I think they raised the 24 question as regulators always raise questions, Page 60 1 but I'm not sure they had reached the conclusion 2 that that was the case. 3 Q. Do you recall whether or not 4 the German government ever concluded that 5 Fluoxetine was activating, as opposed to just 6 raising the question? 7 A. I don't recall that they ever 8 reached the conclusion that it was activating. 9 Q. You said that they raised the 10 question like other regulatory agencies raise the 11 question. Did any other regulatory agency, 12 either here in the United States or outside the 13 United States, to your knowledge raise the 14 question as to whether or not Fluoxetine was 15 activating? 16 A. Let me clarify my statement. 17 I said the German government, as other regulatory 18 agencies, raise questions. I'm not saying that 19 numerous other regulatory agencies -- 20 Q. That's not what I'm asking, 21 I'm asking -- 22 A. I want to make sure that it 23 was understood what I said. 24 Q. My question is, to your Page 61 1 knowledge had any other regulatory agency raised 2 the question of whether or not Fluoxetine was 3 activating or caused suicidality? 4 A. You mean at that time? 5 Q. At any time. 6 A. Well, obviously the questions 7 came up about suicidality much later than the 8 regulatory agencies were involved in the U.S. 9 Q. Okay. Other than the 10 questions raised by Doctor Teicher's article in 11 the beginning of 1990, let's say before 1990, are 12 you aware of any other regulatory agency that 13 raised the question, either whether or not 14 Fluoxetine is activating or causes suicidality or 15 increases suicidality? 16 A. Not any more than their 17 routine evaluation. 18 Q. Including their routine 19 evaluation. 20 A. Scientific -- well, I think 21 they all would have looked at the data and asked 22 those kinds of questions, raised those questions 23 themselves. But I can't recall any situation in 24 which that was raised as a major issue. Page 62 1 (PLAINTIFFS' EXHIBIT NO. 1 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. Have you had a chance to 5 review Exhibit 1, Doctor? 6 A. No, I haven't, actually, 7 nobody gave me any instructions about what to do 8 with it. 9 Q. Go ahead and take your time 10 and read through it. 11 MR. MYERS: You have to be careful 12 about that. 13 Q. Doctor, have you had a chance 14 to review Exhibit 1 now? 15 A. Yes. 16 Q. Have you seen the exhibit 17 before? 18 A. I don't recall seeing it. 19 Q. Okay. It purports to be an 20 E-mail written by J. Schenk and Hans Weber dated 21 June 26, 1984, correct? 22 A. Correct. 23 Q. And what is the subject matter 24 of the E-mail? Page 63 1 A. It's a very long document 2 spelling out specific items that they felt they 3 needed to address the questions that the BGA had 4 raised. 5 Q. Okay. And those questions 6 would have been raised as of, at least, June 26, 7 1984, correct? 8 A. Yes, it looks -- it appears 9 that's the case. 10 Q. The first paragraph says this 11 is to confirm which additional data have been 12 identified to be essential during our discussion 13 at the BGA on June 15, 1984, correct? 14 A. That's correct. 15 Q. Do you know what data the BGA 16 was given to review when the application for 17 marketing of Fluoxetine in Germany was first 18 submitted? 19 A. I don't know specifically what 20 was contained in the BGA application. 21 Q. Okay. Do you know generally 22 what would have been contained? 23 A. It would have been based on 24 the U.S. application. Page 64 1 Q. Okay. Same information that 2 was given to the FDA with regards to clinical 3 trials that had been conducted on Fluoxetine 4 prior to that time? 5 A. I really don't know enough to 6 say that it was exactly the same or not. The 7 core information would have been the same 8 information that was provided to the FDA, and 9 that information would have been put into a 10 format that was compatible with the BGA's 11 requirements, which may or may not have included 12 certain other pieces of information they didn't 13 want. 14 Q. When you say they didn't want, 15 you mean the FDA? 16 A. The BGA didn't want. 17 Q. Are you familiar with what 18 information was submitted to the FDA in support 19 of our application -- Lilly's application for 20 approval here? 21 A. I mean in general terms, yes. 22 I can't be specific, I don't know the new drug 23 application in detail, but obviously that's a 24 public record. Page 65 1 Q. Can you tell me what you 2 recall or what you know generally was submitted 3 to the FDA? 4 A. Well, it would have been the 5 usual components from a clinical trial 6 perspective, it would have been pivotal trials to 7 support safety and efficacy of the drug. 8 Q. What is a pivotal trial? 9 A. It's a loose definition, but 10 the way it's commonly used are the trials that 11 are central to confirming efficacy, primarily. 12 Safety is a more collection of more extensive 13 data from many trials. 14 Q. Are you familiar with which 15 studies performed on Fluoxetine for depression 16 are considered pivotal studies? 17 A. I can't recite which of the 18 studies were considered the pivotal studies in 19 the NDA. 20 Q. Who makes a determination of 21 whether or not a study is pivotal? 22 A. The FDA would decide whether 23 that study -- again, it's a loose term, but the 24 FDA would conclude which studies they felt Page 66 1 justified the claims of efficacy. 2 Q. Do you know how many studies 3 were submitted to the FDA by Lilly on 4 preapproval? 5 A. I don't know the exact number. 6 Q. Do you know how many studies 7 were chosen by the FDA to be considered pivotal 8 in support of the application? 9 A. The requirement for approval 10 is two well-controlled trials. So from the group 11 of studies that were submitted to the FDA, they 12 had to reach the conclusion that at least two of 13 those were both well controlled, and also met the 14 necessary requirements to demonstrate efficacy 15 from a statistical perspective. There may have 16 been more than that that they chose. 17 Q. Do you know if they chose more 18 than two? 19 A. I don't know how they -- I'm 20 not sure it's that rigid a process, but there had 21 to at least be two. 22 Q. Two that they felt supported 23 the claim that the drug was safe and efficacious? 24 A. Yes. Page 67 1 Q. Do you know if the same trials 2 that were submitted to the FDA were also 3 submitted to the BGA? 4 A. To my knowledge, the same 5 trials would have been submitted, but I can't 6 personally confirm that. 7 Q. Do you know of any trials that 8 were submitted to the BGA that were not submitted 9 to the FDA? 10 A. I don't know of any trials 11 that were not submitted to the BGA, or vice 12 versa, I don't know -- as far as I know, all of 13 the same trials were submitted. 14 Q. To both entities? 15 A. Yes. 16 Q. If you look at number two on 17 page one, it says, "The BGA stated that there is 18 a disagreement between patient's and doctor's 19 judgment of efficacy." Do you see that? 20 A. Yes. 21 Q. Since in their opinion the 22 patient's impression is more important, we have 23 to demonstrate correlation between SCL 58 and 24 HAMD and CGI and PGI response. Do you see that? Page 68 1 A. Yes. 2 Q. Do you recall that issue being 3 brought up by the BGA? 4 A. I don't recall that issue 5 specifically. 6 Q. Do you recall it generally? 7 A. That's a common problem in 8 clinical trials, that those kinds of 9 measurements, very subjective measurements, don't 10 always correlate perfectly. 11 Q. Do you know if that issue was 12 raised by the FDA, the lack of correlation 13 between the patient's and the doctor's judgement 14 of efficacy? 15 A. I don't recall that being a 16 specific issue by the FDA. 17 Q. If you look on the second 18 page, number four, it says in the controlled 19 trials we had all the contraindications of 20 tricyclic comparitors, for example glaucoma, 21 urinary retention, severe cardiovascular disease, 22 et cetera, as exclusion criteria. Do you see 23 that? 24 A. Yes. Page 69 1 Q. We have to demonstrate, 2 perhaps by analysis of open trails, that 3 Fluoxetine is safe in such patients, otherwise we 4 will have to name those exclusion criteria also 5 as contraindications in the package insert, 6 correct, is that what it says? 7 A. Yes. 8 Q. It goes on to say, The same 9 applies to serious suicidal risks, bipolar 10 illness, hypertensive patients treated with 11 certain hypertension drugs, history of seizures, 12 and hyperthyroidism. Correct? 13 A. Yes. 14 Q. Do you know, were patients who 15 posed a serious suicidal risk, were they excluded 16 from the clinical trials on Fluoxetine? 17 A. The wording was that patients 18 that in the minds of the physicians represented 19 severe suicidal risk could not be included for 20 ethical reasons. That was true in most studies, 21 but not all studies, as I recall. The second 22 thing to point out is that though that exclusion 23 was worded, there were clearly patients that had 24 suicidal ideation as indicated by other measures. Page 70 1 Q. By the Ham-D-3? 2 A. I don't know which Ham-D item, 3 but it was Ham-D. 4 Q. It was a single Ham-D item? 5 A. Well, at least that. There 6 may have been other parts of the scales that also 7 suggested that they were -- they had some 8 suicidal ideation, but they weren't necessarily 9 considered at severe suicidal risk, eminent 10 suicidal risk by the doctors. 11 MR. SMITH: Was the term severe or 12 serious? 13 THE WITNESS: I don't know the exact 14 term, I'm sorry, I can't say exactly. But the 15 fundamental concept was that ethically you 16 couldn't justify putting a patient in a trial if 17 they were considered to be an eminent suicidal 18 risk. 19 Q. Why? 20 A. Because they may commit 21 suicide when you treated them with placebo, you 22 weren't actually treating them. 23 Q. In those studies where serious 24 suicidal risk was not an exclusion criteria, how Page 71 1 was it decided that it would not be an exclusion 2 criteria for that particular study? 3 A. I don't know exactly what 4 criteria or what -- who made that final decision. 5 Those decisions were usually up to the 6 investigator. 7 Q. The decision as to whether or 8 not to exclude serious suicidal risk patients 9 were made by the investigator? 10 A. I'm saying in those -- you 11 said in those exceptional studies in which it was 12 not excluded, that -- I don't know exactly how it 13 was done, but obviously it would have had to have 14 had the consent of the investigator or he 15 wouldn't have done the trial. 16 Q. Well, were there reasons why 17 the exception was made in some cases to allow 18 serious suicidal risk patients into a study as 19 opposed to excluding them? 20 A. I'm sure there were reasons, 21 but I don't know what those reasons were in any 22 specific situation. 23 Q. Did you ever draft protocols 24 for depression trials in Fluoxetine? Page 72 1 A. I don't ever recall drafting a 2 protocol. 3 Q. Did you have any input on what 4 was to be contained in any protocols on 5 Fluoxetine? 6 A. Yes. 7 Q. Which types of trials? 8 Depression trials I'm talking about. 9 A. Right. Well, virtually all of 10 the protocols were signed off by the director of 11 the division. 12 Q. Okay. Did you ever reject a 13 protocol that was submitted to you for signing 14 off on? 15 A. I'm sure I did. 16 Q. Do you recall any? 17 A. I don't recall any specific 18 ones. 19 Q. Are you aware of any 20 outpatient depression studies done on Fluoxetine 21 where serious suicidal risk was not an exclusion 22 criteria? 23 A. Again, I don't know the 24 specific studies, but my recollection is there Page 73 1 were studies in which that suicidal -- the 2 wording about severe suicidal risk in the mind of 3 the investigator was not included, in other words 4 that exclusion did not exist. 5 Q. What I want to know, Doctor, 6 is if you are aware of any reason by Lilly, okay, 7 any reason Lilly would not include as an 8 exclusion criteria serious suicidal risk? I 9 don't care about the investigators' judgment, or 10 anything like that, I want to know why it is that 11 some of the studies had serious suicidal risk 12 excluded and others did not. 13 A. Well, there were some studies 14 of suicidal patients, I mean, in which you needed 15 to include such patients. That might be a reason 16 that such an exclusion was not included. 17 Obviously one would have to construct that 18 protocol in a very different way to ensure that 19 those patients were followed much more closely. 20 Perhaps they were in-patients or whatever, but 21 that would be a reason why one might not include 22 such an exclusion twisted in the words. 23 Q. Okay. Studies of suicidal 24 patients, how many of those to your knowledge Page 74 1 were performed by Lilly? 2 A. I don't know. There's one 3 that comes to mind that Doctor Montgomery did, 4 but I'm not sure of the exact design of that 5 trial. 6 Q. Doctor Stewart Montgomery from 7 England? 8 A. Yes. 9 Q. Was that a suicide prophylaxis 10 study? 11 A. Well, again, I'm not sure 12 exactly what the design of the trial was, but 13 that was my recollection in general. 14 Q. Do you know if that study was 15 actually performed? 16 A. I believe it was. 17 Q. Do you know if that study was 18 ever published or the results of that study was 19 ever published? 20 A. I don't know. 21 Q. Do you know what the results 22 of that study were? 23 A. Again, my recollection of the 24 results was that they were -- they indicated that Page 75 1 in fact Fluoxetine was effective in such 2 patients. 3 Q. For treating depression? 4 A. For treating depression, yes, 5 in suicidal -- in those suicide prone patients. 6 But again, that's a recollection, I don't 7 remember the details. 8 Q. Do you recall whether or not 9 anybody suffered increased suicidality during 10 that study? 11 A. I don't recall that that 12 happened at all in that study. 13 Q. Okay. Was that -- were the 14 results of that study submitted to the drug 15 advisory committee in 1991? 16 A. I don't know -- I'm not even 17 sure that the study was completed at that time, I 18 just don't remember the timing. If it had been 19 completed and data were available, it would have 20 been included in the information provided to the 21 FDA. 22 Q. Okay. 23 A. There was nothing that was 24 withheld from the FDA with regard to suicidality. Page 76 1 Q. Do you know if that study was 2 even mentioned to the FDA? 3 A. Again, I don't know that it 4 was or wasn't, I'm just stating the general point 5 that virtually everything that we had any 6 information we had related to suicidality was 7 provided to the FDA. 8 Q. Were you at the advisory 9 committee meeting in 1991? 10 A. Yes. 11 Q. Do you recall any discussion 12 whatsoever of Doctor Montgomery's suicidality 13 study at that meeting, that it was being 14 conducted, that it had been conducted, anything 15 whatsoever? 16 A. I don't recall that 17 discussion, I don't recall. 18 Q. Do you know why it wasn't 19 discussed? Doctor Montgomery was at that 20 meeting, right? 21 MR. MYERS: Excuse me, that was two 22 questions. 23 MS. ZETTLER: Yes, I know. 24 Q. Doctor Montgomery was at that Page 77 1 meeting, was he not? 2 A. I think Doctor Montgomery was 3 at that meeting. 4 Q. Wasn't he a consultant to the 5 committee at that meeting? 6 A. I think he was. Again, I had 7 forgotten, but I think you're right, he was 8 there. 9 Q. Do you know why his 10 suicidality study was not discussed at that 11 meeting? 12 A. I don't think there was any 13 intentional omission of Doctor Montgomery's 14 study, it was just one of those things, like many 15 things, that didn't come into the conversation. 16 Or for all I know, it may have come into the 17 conversation by Doctor Montgomery himself, I just 18 don't remember the details. 19 Q. I read the transcript of that 20 meeting, Doctor, and there was no mention 21 whatsoever of Doctor Montgomery's study, in fact 22 there was no mention whatsoever of Doctor 23 Montgomery ever having conducted clinical trials 24 on Fluoxetine, okay. So what I want to make sure Page 78 1 I understand, is it your testimony that a study 2 performed by Lilly on Fluoxetine, as it relates 3 to suicidality, was something that could just not 4 happen to come up during a meeting on that exact 5 issue before the advisory committee meeting at 6 the FDA? 7 A. Again, I don't know whether 8 Doctor Montgomery's data were even available at 9 that time, I just don't recall the dates in which 10 that data were available. I can tell you the 11 general point, that is that everything related to 12 suicidality was submitted to the FDA, and that if 13 Doctor Montgomery's data were available to Lilly, 14 the FDA would have had those data. Whether they 15 came up in the conversation or not would have 16 been something that either Lilly or the FDA, you 17 know, could have brought up, either side could 18 have brought it up if it were relevant to the 19 discussion at the time. 20 Q. In your opinion would a study 21 on suicidality, such as the one conducted by 22 Doctor Montgomery, be relevant to the issue of 23 whether or not Fluoxetine causes or increases 24 suicidality? Page 79 1 A. Assuming that the data was a 2 well-conducted, relevant, you know, correctly 3 run, accurate study, if it shed light on it, it 4 would be relevant to bring it up. But again, I 5 don't even know that the information was 6 available at that time. 7 Q. Well, documents that we've 8 seen, Doctor, indicate that Doctor Montgomery's 9 study was conducted between 1988 and 1990. Is 10 there any reason why at least preliminary data 11 would not have been available to Lilly or the FDA 12 at that time, in 1991? 13 A. Again, I don't know, there may 14 be all kinds of reasons why the data weren't 15 available, including Doctor Montgomery himself, I 16 don't know. I don't know what, again, what 17 information Doctor Montgomery had, how complete 18 his data base was at the time, how accurate your 19 dates are, I just don't know any of those things. 20 Q. Okay. Would the protocol for 21 such a study be created by Lilly? 22 A. Probably in that situation, 23 no, that probably would have been Doctor 24 Montgomery's protocol that he would have created. Page 80 1 It ultimately would have, if we provided drug to 2 Doctor Montgomery, it would have been approved by 3 Lilly. 4 Q. I'm sorry, go ahead. 5 A. No, go ahead. 6 Q. Why would such a protocol be 7 developed by Doctor Montgomery as opposed to 8 somebody at Lilly? 9 A. Doctor Montgomery is a well 10 known scientist in that area, he had a scientific 11 interest in the question, and he would have 12 proposed the study to Lilly to be done as a 13 reasonable scientific question. 14 Q. To your knowledge was Doctor 15 Montgomery's study at least started before or 16 after Doctor Teicher's article came out in 17 January, February of 1990? 18 A. Well, by what you have said, 19 it would have been started before Doctor 20 Teicher's paper came out. 21 Q. But do you have any 22 independent recollection of when that study was 23 begun? 24 A. I don't, no, I don't. Page 81 1 Q. To your knowledge -- or you 2 don't know either way whether or not Doctor 3 Montgomery's study was ever published? 4 A. Again, I don't know that it 5 was or wasn't. 6 Q. Do you know whether or not the 7 German government has ever required 8 contraindicating the use of Fluoxetine in 9 patients who pose a serious suicidal risk? 10 A. Could you please -- labeling 11 is very detailed wording, and I guess -- can you 12 rephrase the question so -- 13 Q. Sure. Has the German 14 government, in any of their labeling or any of 15 their official documents related to the 16 prescribing of Fluoxetine in Germany, have they 17 ever listed serious suicidal patients as 18 contraindicated patients for Fluoxetine, in other 19 words don't give Fluoxetine to people who pose a 20 serious suicidal risk? 21 A. I don't believe there's ever 22 been such a, quote, contraindication, end quote. 23 Q. Okay. Do you know of any 24 limitations whatsoever that the German government Page 82 1 has dictated or recommended with using Fluoxetine 2 in patients who pose a serious suicidal risk? 3 A. The wording in many package 4 inserts, and I don't know whether it's included 5 in the German package insert, indicates that 6 patients who are depressed may be at suicidal 7 risk, and therefore caution should be exercised 8 in treating such patients because of the concern 9 about suicide. That's a statement that's in 10 almost all antidepressants, and that kind of a 11 statement would have been included in many Prozac 12 package inserts as well as with other compounds. 13 But I just don't know about Germany, per se, I 14 don't know what the German package insert was. 15 Q. Do you consider the warning 16 that you described that exists in the United 17 States package insert regarding suicide and 18 depressed patients as a warning cautioning 19 doctors on using Fluoxetine specifically with 20 suicidal patients? 21 A. No, not specifically with 22 Fluoxetine, it exists with many other 23 antidepressants. 24 Q. It's really kind of a generic Page 83 1 warning regarding -- or statement regarding 2 suicidal patients, using any medication 3 whatsoever? 4 A. It's a general statement about 5 depressed patients than the fact that depressed 6 patients may be suicidal. 7 Q. And the warning, as it exists 8 for, say, tricyclic antidepressants is really 9 there to indicate to doctors that you shouldn't 10 give them too much medication at once so they 11 can't overdose themselves on it, or there's less 12 of a chance of overdosing themselves on the drug, 13 correct? 14 A. Well, the general statement is 15 that depressed patients may be at suicidal risk, 16 so yes, they could commit suicide by taking too 17 much medication. But the statement reemphasizes 18 the point that suicide is part of -- or potential 19 suicide is part of depression. 20 Q. But it doesn't caution -- the 21 Fluoxetine warning or suicide statement does not 22 caution the physician on using specifically 23 Fluoxetine with suicidal patients because it may 24 increase their suicidality, right? Page 84 1 A. That's correct, because 2 there's really never been any evidence that there 3 was any increase in suicidality with Fluoxetine 4 versus any other -- 5 MS. ZETTLER: Motion to strike that 6 response, everything after that's correct, as 7 being self-serving and nonresponsive. 8 Q. To your knowledge has the 9 German government package insert ever contained a 10 warning or cautionary statement specifically 11 regarding the use of Fluoxetine in suicidal risk 12 patients, besides the generic statement that you 13 were just talking about? 14 A. Not that I recall. 15 Q. Would it surprise you if it 16 did? 17 A. Would it -- I'm sorry? 18 Q. Would it surprise you if the 19 German government included a cautionary statement 20 regarding the use of Fluoxetine on suicidal risk 21 patients? 22 A. It depends on what that 23 statement said. 24 (PLAINTIFFS' EXHIBIT NO. 2 WAS Page 85 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 A. I'm supposed to read this? 4 Q. You can glance. You don't 5 have to read it word for word, I'm going to 6 direct your attention to page two of the actual 7 document, the section called risk patients. 8 A. Risk patients, yes. 9 Q. So if you want to read that 10 section. Have you had a chance to review that 11 page two of Exhibit Number 2, Doctor? 12 A. Yes, I have. 13 Q. Okay. Let me tell you what 14 this is, Doctor. We have obtained a copy of the 15 most recent package insert for Fluctin, which you 16 may or may not know is Fluoxetine as it's 17 marketed in Germany. We have had the package 18 insert that came to us in German translated to 19 English, okay, and this is the English 20 translation. Page three of the exhibit, but page 21 two of the translation, has a section called risk 22 patients. Do you see that? 23 A. Yes. 24 Q. And the fourth bullet point Page 86 1 down says risk of suicide, colon, does it not? 2 A. Yes. 3 Q. After that it says Fluctin 4 does not have a general sedative effect on the 5 central nervous system, therefore for his/her own 6 safety, the patient must be sufficiently observed 7 until the antidepressive effect of Fluctin sets 8 in, correct? 9 A. Yes. 10 Q. Taking an additional sedative 11 may be necessary. Do you see that? 12 A. Yes. 13 Q. This also applies in cases of 14 extreme sleep disturbances or excitability, is 15 that correct? 16 A. Yes. 17 Q. Were you aware that the 18 package insert in Germany contained this 19 cautionary statement? 20 MR. MYERS: At what point in time? 21 MS. ZETTLER: At any point in time. 22 A. I was not aware that it did 23 include such a statement. But again, I don't 24 know whether it did at the time that I was even Page 87 1 involved if this was the most recent package 2 insert. 3 Q. Does it surprise you that the 4 package insert in Germany contains this 5 cautionary statement now, or at least as of the 6 time of this package insert? 7 A. Again, this statement does not 8 surprise me, this statement basically says what I 9 think I said. 10 Q. Which was what? 11 A. Which was that it is not -- it 12 is not a sedating antidepressant. 13 Q. Okay. Do you agree with the 14 German government's suggestion that, at least in 15 some cases, we have a patient who is a risk of 16 suicide, you may want to prescribe an additional 17 sedative on top of Fluoxetine? 18 A. I'm not sure that there's any 19 evidence to support that statement. 20 MR. DOWNEY: Okay. Do you know that 21 there's no evidence? 22 MR. MYERS: Hold on. Now Judge Godich 23 has asked us to conduct the deposition in a 24 certain way and has made certain instructions. Page 88 1 Now we can't have more than one person asking 2 questions at one time, Mister Downey. 3 MR. DOWNEY: All right. 4 MR. MYERS: I'm trying to be fair to 5 you and fair to the witness, so let's just have 6 one person. 7 MR. DOWNEY: I understand, I just want 8 a quick clarification, but I'll have Ms. Zettler -- 9 MS. ZETTLER: Can you read it back. 10 (THE COURT REPORTER READ BACK THE 11 REQUESTED TESTIMONY.) 12 Q. (BY MS. ZETTLER) So, Doctor, 13 is it your testimony that the German government 14 is recommending that at least in some cases with 15 patients who pose a suicidal risk, that 16 concomitant sedatives be given based on no 17 evidence? 18 A. I'm saying I'm not aware of 19 any evidence to support this point. They may 20 have some evidence that I'm not aware of. 21 Q. So some evidence may have been 22 submitted to them by Lilly that supports their 23 concern that at least in some patients a 24 concomitant sedative may be necessary to prevent Page 89 1 suicide in a patient who poses a suicidal risk? 2 A. I'm afraid I'm going to have 3 to ask you to repeat that because it was a long 4 statement and I want to make sure I'm not 5 answering the wrong question. 6 Q. Sure. 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED TESTIMONY.) 9 A. I don't believe there was of 10 any data submitted by Lilly that even studied the 11 question of concomitant sedatives in suicidal 12 patients. That was your specific question, I 13 believe. I don't think Lilly ever submitted any 14 information that would support this 15 recommendation. 16 Q. Well, it appears from Exhibit 17 Number 1, at least, that the German government is 18 raising these questions after their review of 19 information that was given to them by Lilly, does 20 it not? 21 MR. MYERS: Which of the several 22 questions? 23 MS. ZETTLER: Any of them. 24 Q. It appears that the questions Page 90 1 were raised by the government after their review 2 of the information submitted to them by Lilly, 3 correct? 4 A. But I think it may be 5 incorrect to conclude that the German -- that the 6 BGA would base all of their knowledge of 7 psychiatry and the treatment of suicidal patients 8 based on the data that Lilly submitted on 9 Fluoxetine. 10 Q. I'm not implying that, Doctor, 11 I'm saying that the questions raised in Exhibit 1 -- 12 A. Yes. 13 Q. -- appear to have been raised 14 by the BGA after a review of -- after reviewing 15 documents or data submitted to it by Lilly on 16 Fluoxetine. I'm not saying that's the only thing 17 they took into consideration, I'm saying -- 18 A. Right. 19 Q. -- I'm saying the questions 20 were raised after the document or data was 21 submitted by Lilly, after the application was 22 made, correct? 23 A. That would appear to be the 24 case, yes. Page 91 1 Q. And it also appears to be the 2 case that a lot of these questions that they had 3 were raised by the data that they reviewed that 4 was given to them by Lilly, does it not? 5 A. I'm sure that some of the 6 questions were raised based on the data that 7 Lilly submitted. 8 Q. So why is it, if you know, 9 that the German government is raising the 10 question and believes, apparently from their 11 package insert recommendation, that at least in 12 some cases Fluoxetine should be given with a 13 sedative on suicidal risk patients if there's no 14 evidence of that? 15 A. Well, again, maybe I better 16 ask you to repeat the question. 17 Q. Let me ask it an again, there 18 may be a better question. Why is it that if 19 there's no evidence of Fluoxetine being 20 activating, like you said in your opinion, or 21 worsening suicidality in patients who pose a 22 suicide risk, why is it that the German 23 government feels it's necessary to put that 24 cautionary statement in the package insert as it Page 92 1 exists today, if you know? 2 A. Well, I'm not sure that that's 3 what this package insert says. I believe it says 4 it may be necessary, and your wording was it is 5 necessary, and this -- that's not what the German 6 package insert says. 7 Q. Well, I didn't mean -- if I 8 said -- I didn't mean to say that it is 9 necessary, I said it may not be necessary in some 10 patients. I mean I'll even give you that much, 11 that it's not necessary across the board. But 12 there are some patients that it may be necessary 13 to prescribe a concomitant sedative with 14 Fluoxetine if those patients pose a serious 15 suicidal risk? 16 A. Again, I don't believe that 17 the German government is basing this on any 18 scientific data, I'm not aware of any scientific 19 data. I think it's really speculation on their 20 part and their practice of psychiatry, but there 21 are no -- to my knowledge, there are no data to 22 support the point. 23 Q. Let me help you out here a 24 little bit, I think you're going to find that Page 93 1 that's not the indication. 2 A. My memory is not perfect. 3 (DISCUSSION OFF THE RECORD.) 4 (PLAINTIFFS' EXHIBIT NO. 3 WAS 5 MARKED FOR IDENTIFICATION AND 6 RECEIVED IN EVIDENCE.) 7 Q. Have you had a chance to 8 review Exhibit 3? 9 A. I have. 10 Q. Do you recognize the exhibit? 11 A. I really don't. 12 Q. Okay. You were listed as a 13 primary recipient on this, are you not? 14 A. Yes. 15 Q. Okay. And at the time you 16 were still in Indianapolis, correct? 17 A. Yes. 18 Q. This is dated April 2, 1985, 19 is it not? 20 A. Yes. 21 Q. It appears to be an E-mail by 22 Doctor Johanna Schenk to yourself as well as 23 other -- a number of other Lilly employees, 24 correct? Page 94 1 A. It doesn't appear to be an 2 E-mail to me. 3 Q. A memo? 4 A. Yes. 5 Q. And who is D. E. Thompson? 6 A. I believe that's David 7 Thompson. 8 Q. Who is David Thompson? 9 A. He's in the marketing area, I 10 think he currently is responsible for licensing. 11 Q. Okay. When you say licensing, 12 what do you mean? 13 A. I mean licensing in new 14 compounds. 15 Q. Okay. Has he always been, at 16 least before the licensing position, was he 17 always in the marketing area to your knowledge? 18 A. I don't know all of the jobs 19 that Doctor Thompson has had. 20 Q. He's a medical doctor? 21 A. No, he isn't. Did I say 22 doctor? 23 Q. Yes. 24 A. I'm sorry, Mister Thompson. Page 95 1 Q. You're thinking of Leigh 2 Thompson. 3 A. Yes. No. 4 Q. Is he a Ph.D? 5 A. No, I don't believe so. 6 Q. This exhibit purports to be a 7 report on the Fluoxetine working session of April 8 29th and 30th, 1985 in Bad Homburg, right? 9 A. Yes. 10 Q. And it lists a bunch of 11 participants, including a Doctor Kern, an 12 S. Heymanns, B. Von Keitz, and Doctor J. Schenk, 13 correct? 14 A. Yes. 15 Q. Do you know these people, 16 Doctor Kern, S. Heymanns, B. von Keitz, and 17 Doctor Schenk? 18 A. I know the names, the last 19 three names. Doctor Kern, I may have met, I 20 really don't recall the individual. 21 Q. Who is S. Heymanns? 22 A. She's a -- I think it's a she, 23 is a regulatory person in Germany, I believe. 24 Q. Regulatory, you mean an Page 96 1 employee of the BGA or regulatory as an employee 2 of Lilly? 3 A. No, an employee of Lilly in 4 the regulatory group. 5 Q. How about B. von Keitz? 6 A. I believe that she's also a 7 member of the regulatory group at Lilly. 8 Q. What position did Doctor 9 Schenk hold with Lilly at the time of this memo, 10 April of '85, if you know? 11 A. My recollection is that she 12 was the monitor in Germany for Fluoxetine. 13 Q. The medical monitor? 14 A. Yes. 15 Q. Similar to Doctor Stark's 16 position? 17 A. Yes. 18 Q. How about Doctor Kern, was 19 Doctor Kern an employee of Lilly to your 20 knowledge? 21 A. To my knowledge, no. 22 Q. You say you may have met 23 Doctor Kern, do you have a recollection of Doctor 24 Kern at all? Page 97 1 A. No, I really don't. The name 2 sounds familiar, but I really can't remember. 3 Q. The objective of the meeting 4 was to make a Professor Blank and his co-worker 5 familiar with Fluoxetine data so that he is in a 6 better position to give best advice as a 7 consultant to the company in the registration 8 process of Fluoxetine. Do you see that? 9 A. Yes. 10 Q. Do you know who Professor 11 Blank is? 12 A. I don't. 13 Q. Doctor Winoker ever work out 14 of Berlin to your knowledge? 15 A. I don't believe Doctor Winoker 16 ever worked out of Berlin. 17 Q. Would you look at the last 18 page of the exhibit, the last paragraph. It says 19 however, bear in mind without in-patient data, 20 even if all other data are satisfactory, it is 21 Herrmann's opinion that we at best get a limited 22 indication approval. Does that refresh your 23 recollection as to who Doctor Herrmann is? 24 A. It really doesn't, I'm sorry. Page 98 1 Q. Okay. The next section of the 2 exhibit is data reviewed. Under number one it 3 says an original documentation submitted March 1, 4 1984. Do you see that, under the data reviewed 5 section at the bottom of the page? 6 A. Yes. 7 Q. Do you know what original 8 documentation was submitted to Professor Blank on 9 March 1, 1984? 10 A. I don't. 11 Q. How about under number two, an 12 analysis of pooled studies, Fluoxetine versus 13 Imipramine versus placebo, protocol number 14 twenty-seven, submitted October 26, 1984. Do you 15 recall an analysis of pooled studies of 16 Fluoxetine versus Imipramine versus placebo or 17 otherwise known as protocol number twenty-seven 18 being submitted to a professor for review in 19 regards to the questions raised by the BGA? 20 A. I don't recall that, no. 21 Obviously it was, but I don't recall the details 22 of what that was. 23 Q. It states after that, under 24 outcome, Professor Blank left an opinion of Page 99 1 twenty-one typewritten pages, correct? 2 A. Yes. 3 Q. And it appears that the 4 essential points or some of the points of his 5 opinions are listed in the rest of the memo, 6 correct? 7 A. Yes. 8 Q. Is it your understanding from 9 this memo that whoever Professor Blank is 10 rendered opinions in the form of twenty-one 11 typewritten pages on the original documentation 12 submitted to he or she on March 1, 1984, and the 13 analysis of pooled studies of Fluoxetine versus 14 Imipramine versus placebo, protocol number 15 twenty-seven, is that how you read this? 16 A. From my reading of the 17 document, yes. 18 Q. Okay. The first section of 19 Doctor Schenk's, at least, review of Professor 20 Blank's opinion is on efficacy, is it not? 21 A. Yes. 22 Q. And at least according to 23 Doctor Schenk, Professor Blank felt that 24 Fluoxetine's onset of action was later than that Page 100 1 of Imipramine, correct? 2 A. That's what's indicated here, 3 yes. 4 Q. Which essentially means it 5 took longer for the antidepressant effect of 6 Fluoxetine to set in than Imipramine's 7 antidepressant effect, correct? 8 A. That apparently is this 9 reviewer's impression. 10 Q. The second point under 11 efficacy was that it was Doctor Blank's opinion 12 that the initial potency of Fluoxetine was 13 inferior to that of Imipramine, correct? 14 A. Again, that's what these words 15 are, yes. 16 Q. And under that, it says the 17 overall response rate was identical, correct? 18 A. That's what's indicated here, 19 yes. 20 Q. Would you take that to mean 21 that the overall response rate of patients on 22 Fluoxetine and patients on Imipramine was 23 identical? 24 A. Yes, that's the way I would Page 101 1 read it. 2 Q. Essentially the same number of 3 responders to each drug? 4 A. Yes. 5 Q. The drop-out rate for 6 Fluoxetine because of lack of efficacy was only 7 slightly higher than that of Imipramine, correct? 8 A. Yes. 9 Q. So slightly more patients on 10 Fluoxetine dropped out of the studies because of 11 lack of efficacy than patients on Imipramine, 12 correct? 13 A. That's what's indicated here, 14 yes. 15 Q. Then it goes on to say, in 16 capital letters, Fluoxetine is an effective 17 antidepressant in outpatients suffering from 18 preferably endogenous depression, correct? 19 A. Yes. 20 Q. Do you know what preferably 21 endogenous depression means? 22 A. Again, I can only speculate as 23 you can speculate. 24 Q. In other words -- Page 102 1 A. I think it's a poorly worded 2 indication that they felt endogenous depression 3 was more effectively treated. 4 Q. Than other forms of 5 depression? 6 A. That's the implication. 7 Q. The next category is safety. 8 Do you see that? 9 A. Yes. 10 Q. Under the first point of 11 safety, it's initially only sightly higher 12 incidence of signs of activation or no difference 13 at all compared to placebo, correct, is that what 14 it says? 15 A. Yes, that's what it says. 16 Q. Do you take that to mean that 17 this doctor felt that there was only a slightly 18 higher incidence of signs of activation with 19 Fluoxetine? 20 A. Well, it says -- 21 Q. As compared to Imipramine, I'm 22 sorry. 23 A. No, I'm sorry, that isn't what 24 it says here, it says initially only slightly Page 103 1 higher incidence of signs of activation or no 2 difference at all. To me, I read that as saying 3 that there is slightly higher or no difference 4 compared to placebo. That's the way I read that 5 statement. 6 Q. So compared to placebo, not -- 7 A. Compared to placebo. 8 Q. Not Imipramine? 9 A. There was no difference in the 10 incidence of activation. 11 Q. Under that it says, Imipramine 12 and Fluoxetine have both components, activation 13 as well as initial sedation, correct? 14 A. Yes. 15 Q. Initial sedation is more 16 pronounced under Imipramine, correct? 17 A. Yes. 18 Q. If you skip down a couple to 19 where it says Fluoxetine causes a relevantly 20 minor incidence of drop outs because of side 21 effects, correct? 22 A. It says -- it says causes a 23 relatively smaller incidence of drop outs because 24 of side effects. Page 104 1 Q. No, I think the word is 2 relevantly. 3 A. Causes relevantly smaller -- I 4 thought you said minor, I'm sorry. 5 Q. No. We're both having 6 problems reading. 7 A. Read too much. 8 Q. Fluoxetine causes a relevantly 9 smaller incidence of drop outs because of side 10 effects, correct? 11 A. Yes. 12 Q. Do you know if that's compared 13 to placebo or Imipramine? 14 A. I can't tell from this, and 15 without looking at the data base, I can only 16 speculate, although I would guess it was related 17 to Imipramine. 18 Q. Under that it says, in capital 19 letters, still not resolved is the fact that 20 suicide attempts have been observed more 21 frequently on Fluoxetine as compared to 22 Imipramine, correct? 23 A. Yes. 24 Q. Then it goes on to say, in Page 105 1 parentheses, only epidemiologic data or 2 literature on other antidepressants may help to 3 identify whether it happened by chance that 4 incidence of suicide attempts was abnormally high 5 on Fluoxetine or abnormally low under 6 comparators, correct? 7 A. Yes. 8 Q. Do you know whether or not 9 this professor reviewed any information or any 10 other study information in addition to the pooled 11 data of protocol number twenty-seven? 12 A. There's no way I would know 13 that. 14 Q. How would you find that out if 15 you wanted to know that, who would you ask? 16 A. I don't know that it would be 17 possible. You would have to go back to the 18 authors of this memo. 19 Q. Does Lilly keep records on 20 what information it submits to various regulatory 21 agencies? 22 A. There are records kept. I 23 don't know where those records would be held for 24 something like this, and I'm not sure this was a Page 106 1 submission to a regulatory authority. 2 Q. That's a separate question. 3 I'm asking if they keep records of actually what 4 data is submitted to say the BGA. 5 A. Yes. 6 Q. Do you know where that 7 information would be kept? 8 A. You're talking about 1993, 9 when I left, or what? 10 Q. No, when you first became 11 director of European clinical investigations. 12 A. I couldn't answer where the 13 records would have been kept for submissions to 14 the Germans in 1984 or whatever it was. 15 Q. How about in your position as 16 director of, I believe it was, clinical trials 17 and regulation -- hold on -- executive clinical -- 18 executive director of clinical investigations and 19 regulatory affairs in 1989 and through 1991? 20 A. Well, all submissions at that 21 time to the FDA were kept in the U.S. regulatory 22 area as formal submissions to the NDA or IND, and 23 those records are kept in that area. 24 Q. How about submissions to the Page 107 1 BGA? 2 A. I'm not sure submissions to 3 the BGA would have been kept there, they may have 4 been kept in the individual affiliates. 5 Q. Bad Homburg, in this case? 6 A. Yes. 7 Q. Do you know what it was about 8 the data that this professor reviewed that made 9 him conclude that there was a higher incidence or 10 higher frequency of suicide attempts on 11 Fluoxetine as compared to Imipramine? 12 A. Could you repeat the question? 13 Q. Sure. What I would like to 14 know is -- if you can tell or if you know what it 15 was about the information that this professor 16 reviewed that made him come to the conclusion set 17 out on page two of the exhibit that still not 18 resolved is the fact that suicide attempts have 19 been observed more frequently on Fluoxetine as 20 compared to Imipramine. 21 A. I don't know exactly, again, 22 what data set he was looking at that led to that 23 conclusion. 24 Q. He did review the protocol Page 108 1 twenty-seven, which were trials comparing 2 Fluoxetine versus Imipramine on placebo, correct? 3 A. That's what -- yes, that's 4 what they said that he reviewed, yes. As well as 5 the original documentation submitted on March 1. 6 Q. So it may have also been 7 something in the original documentation that was 8 submitted to him on March 1, 1984 that made him 9 come to that conclusion? 10 A. I presume. 11 Q. Under that, it says except 12 nausea, Fluoxetine's side effect spectrum is 13 unequivocally more favorable than that of 14 Imipramine, but according to today's knowledge, 15 this is negatively affected by the increased 16 suicidal risk. Do you see that? 17 A. Yes. 18 Q. Do you know if this was a 19 conclusion that the BGA shared with this 20 professor who reviewed this data? 21 A. Do I know whether the BGA 22 shared that view? 23 Q. Right. 24 A. I don't know what the BGA's Page 109 1 view was at this particular point. 2 Q. Under that, in section C, it 3 says benefit slash risk ratio, does it not? 4 A. Yes. 5 Q. It says not unequivocally 6 positive, correct? 7 A. Yes. 8 Q. Again in caps, it says 9 therefore it is of great importance to determine 10 certain type of patients who will better respond 11 to Fluoxetine than to Imipramine so that higher 12 risk might be acceptable. Do you see that? 13 A. Yes. 14 Q. Do you know what that means? 15 A. Well, I mean I can only read 16 the statement as you read it, and it's, I think, 17 pretty self-evident what is being said. 18 Q. So in other words, if you cull 19 out or find a specific type of patient who 20 responds to Fluoxetine better than to Imipramine 21 and market that or include information in the 22 prescribing materials that states that, then the 23 risk -- the higher risk might be acceptable? 24 A. Well, again, I think this is Page 110 1 only this gentleman's -- or lady, I don't know 2 who it is, opinion that -- and I think the whole 3 point about whether there's even a higher risk is 4 still very equivocal throughout the whole 5 document. 6 Q. You think it's equivocal when 7 this person says that still not resolved is the 8 fact that suicide attempts have been observed 9 more frequently on Fluoxetine as compared to 10 Imipramine? 11 A. I think you're misreading that 12 because I think what they're saying is -- there 13 may have been numbers, incidents, but that 14 doesn't mean that in the course of studies that 15 that really represents a difference, it could be 16 a sampling error or could be a, you know, bias 17 introduced by the study or by chance, and I think 18 they go on to explain that in this memo, at least 19 that's the way I read it. 20 Q. Where? 21 A. Only epidemiologic data or 22 literature on other antidepressants may help to 23 identify. That statement says that they aren't 24 concluding that those numbers are meaningful, Page 111 1 they're saying only additional data will allow us 2 to clarify that point. 3 Q. Are you sure that they're 4 saying that and that's not Doctor Schenk's 5 comment thrown in? 6 A. I think that applies to the 7 whole document in the same -- in the questions 8 you asked me. I can't be any more sure of what's 9 said here positively or negatively, I can only 10 interpret what I've read here. 11 Q. So it's possible that Doctor 12 Schenk is the one whose opinion it is that it's 13 not resolved, the fact that suicide attempts have 14 been observed more frequently on Fluoxetine as 15 compared to Imipramine is not resolved, may in 16 fact be Doctor Schenk's opinion? 17 A. I think this is all subject to 18 that kind of interpretation, the whole document 19 is. 20 Q. A couple of seconds ago you 21 were talking about how numbers may on the surface 22 appear larger than they are or incidence is 23 larger than it is, but it may be affected by 24 study bias and things of that nature, correct? Page 112 1 A. That study design is critical, 2 just chance probabilities, you know, can happen 3 as well in terms of those kinds of observations. 4 Q. Okay. Isn't that -- can't the 5 same be said for when a study shows that a drug 6 is efficacious on the surface, that it may be due 7 to study biases and design biases and errors, and 8 things of that nature? 9 A. I think if studies are, you 10 know, poorly designed, they're always subject to 11 error, whether you're evaluating efficacy or 12 safety. 13 Q. Do you have any reason to 14 believe that protocol twenty-seven was poorly 15 designed? 16 A. I have no reason to believe, 17 but again I'm not sure what protocol twenty-seven 18 is. But again, there's nothing specific that I'm 19 aware of on protocol twenty-seven because I don't 20 have enough information. 21 Q. Protocol twenty-seven, Doctor, 22 is the study, a group of studies that was 23 submitted to the FDA in support of efficacy, and 24 was in fact one of the studies that was relied on Page 113 1 by the FDA to support efficacy, okay. If you're 2 going to take my word for that, is there any 3 reason that you think that there is any problem 4 in the study design of protocol twenty-seven? 5 A. In what respect, in any 6 respect? 7 Q. In any respect. 8 A. To my knowledge, there was 9 nothing wrong with the protocol design. 10 Q. Okay. And to your knowledge 11 were the original efficacy studies submitted to 12 the FDA in support of Fluoxetine by Lilly 13 structured or meant to study the incidence of 14 suicidality in patients receiving Fluoxetine or 15 any comparators? 16 A. Well, not -- they weren't 17 specifically designed with that question in mind. 18 There were data that obviously one would gain 19 from those studies to address that question if it 20 came up. 21 Q. Do you know of any rating 22 scale or any other portion of the study that was 23 specifically included to study suicidality as an 24 objective of the study? Page 114 1 A. As a specific objective, only 2 as part of the overall spectrum of the disease 3 depression, and as you know there are subscales 4 within the Hamilton Depression Scale, suicidality 5 is one of those that's a component that is 6 important in assessing treatment of depression. 7 And, so, in that sense, there's a component there 8 that's part of the design. 9 Q. Weren't there scales out there 10 in the mid '80s that were designed specifically 11 to rate suicidality as opposed to just a general 12 overview of a person's depressive state? 13 A. I don't know what those scales 14 were at that particular point, whether they even 15 existed at that particular point. 16 Q. Okay. Besides a design flaw 17 in the protocol or biases that may have been 18 introduced in the conducting of the studies, what 19 other problems or flaws in the study could create 20 a situation like this, at least surface 21 observation, of a more frequently -- frequent 22 incidence of suicidality on Fluoxetine as 23 compared to Imipramine? 24 A. Again, the studies can be Page 115 1 perfectly well designed, very well executed, and 2 simply by chance you can have differences in 3 numbers in the two groups, and that's what 4 statistical analysis is really focusing on, to 5 assess the probability of those observations. So 6 isolated numbers really don't mean very much in a 7 situation like this. 8 Q. If you accept my 9 representation that protocol twenty-seven is a 10 multi-center study -- 11 A. Yes. 12 Q. -- is the chance, statistical 13 chance, that such problems are going to arise 14 likely when you have eight different studies? 15 A. You're going to have to define 16 some of what you mean because it's important that 17 you define what you mean by an outcome, what are 18 you talking about specifically? 19 Q. You say that just by chance, 20 statistically just by chance, it can appear that 21 there's a higher incidence, correct? 22 A. Sure. 23 Q. Is that likely to happen in a 24 study where you have eight separate sites that Page 116 1 are conducting allegedly identical studies? 2 A. It's very likely that such a 3 difference could occur. It doesn't really have 4 to do with how many sites, it has to do with the 5 total number of patients exposed, and you really 6 have to have very large populations when you're 7 talking about relatively rare events. 8 MR. SMITH: How large? 9 Q. What do you define as how 10 large? Give me a minimum. 11 A. You can't do that because 12 unless you define a specific background incidence -- 13 and there are -- 14 MR. MYERS: Paul, hold on, one at a 15 time, okay. Let Nancy ask the questions. 16 MR. SMITH: Now you're coaching the 17 lawyers. 18 MR. MYERS: That's right. 19 Q. Go ahead and finish your 20 answer, Doctor. 21 A. The point still stands, you 22 can't -- there are very good statistical methods 23 by which you can estimate the size of a sampling 24 you need based on background incidence and the Page 117 1 differences you're trying to show, okay? 2 Q. Uh-huh. 3 A. Unless you have that 4 information, you really -- I can't provide an 5 answer to you on that question. 6 Q. Well, what would you consider 7 a large enough sampling? 8 A. What question are you asking? 9 Q. The question, original 10 question on how large -- you're the one that 11 brought up that you would need a large enough 12 sampling to determine whether or not, based on 13 the studies, that there was a higher incidence of 14 Fluoxetine, as I understood it. 15 A. I think it's true that this 16 sample size is too small to to answer that 17 question because the rate is very low. Unless 18 there were a dramatic difference in the 19 incidence, which there was not, you would have to 20 have a much larger population to answer that 21 question. Telling you exactly how many would -- 22 you would have to frame the question so that you 23 gave me the background incidence and the 24 difference that you were trying to demonstrate. Page 118 1 Q. How do you know that it's not 2 a huge difference in incidence here? 3 A. The background numbers were 4 really very small, as I recall them, from those 5 discussions and that time. 6 Q. So now you recall what type of 7 data was submitted. How do you know -- 8 A. No, I really don't know what 9 types of data were submitted, I only have a 10 general memory that the numbers were low. 11 Q. Numbers, meaning numbers of 12 patients included or numbers of suicidality? 13 A. What do you mean by 14 suicidality? 15 Q. Well, I'm trying to find out 16 what you mean, Doctor. You went from telling me 17 that you didn't know anything about this, you 18 didn't recall anything about this, and now you're 19 telling me that you recall that numbers were 20 small. 21 A. No, I don't believe I ever 22 said I didn't know anything about it. You were 23 asking me very specific questions, and I said I 24 did not recall those kinds of details. What I am Page 119 1 saying I do recall, in the discussions about 2 Germany, was that the numbers of these kind of 3 incidents, suicide attempts, were very low, were 4 low. 5 Q. What do you mean by very low, 6 give me -- 7 A. Less than ten. 8 Q. Less than ten? 9 A. I don't know the exact number, 10 but that's what I'm talking about in that kind of 11 a range of numbers. I don't know the exact 12 number. 13 Q. Do you know how many patients 14 in the total pool that was looked at? 15 A. I don't know what pool was 16 looked at here. 17 Q. Do you recall a review of 18 protocol twenty-seven? 19 A. I don't recall a review of 20 protocol twenty-seven. 21 Q. Do you recall what information 22 or what data was looked at to determine how many 23 suicide attempts there were? 24 A. Could you repeat the question? Page 120 1 Q. Sure. You said that there was -- 2 you recall there were less than ten suicide 3 attempts. Do you recall what was looked at to 4 see how many suicide attempts there were to come 5 up with that number of less than ten or anything 6 that was reviewed? 7 A. Look, I'm not -- I don't 8 recall the precise numbers, I only recall in 9 general the numbers were very low. You asked me 10 to frame in general terms what I thought was very 11 low, I said less than ten. I don't know that 12 there were less than ten, I just don't remember 13 those kinds of details, and I don't know how 14 large a population that was taken from. 15 Q. Okay. Do you recall if all of 16 the studies that had been completed at that time 17 were reviewed? 18 A. To my knowledge, all available 19 data -- our routine approach to this would have 20 been all available data would have been reviewed 21 to address this question. So all data would have 22 been reviewed that was relevant to the question 23 that you could actually interpret. 24 Q. Regardless of whether or not Page 121 1 all data had been reviewed or would be reviewed, 2 would all data be used in an analysis? 3 A. Well, all data that would -- 4 could bear on the question scientifically would 5 have been used. It doesn't mean that all data 6 can actually be pooled and used to address the 7 scientific question. 8 Q. But you could run different -- 9 you could pool different types of data, could you 10 not? For instance, you can pool all the 11 double-blind controlled study data, you could 12 then pool in a separate analysis all the open 13 trial studies, correct? 14 A. Well, all of those things were 15 possible. The question of relevance to the 16 question in mind still stands, how relevant are 17 open-label data in determining rates, and the 18 reality is they aren't very useful because 19 there's no comparator for open-label data. 20 Q. Who decides that, who makes 21 that decision that it's not useful for whatever 22 reason -- or relevant, I'm sorry. 23 MR. MYERS: When you say it, do you 24 mean open label? Page 122 1 Q. Looking at open-label studies. 2 A. Well, it depends. Certainly 3 there is use in any data, but it's not useful in 4 determining rates, and that is, you know, too 5 general -- it's not useful in comparing rates. 6 You can determine rates, but you can't compare 7 rates if you've got nothing to compare it to. 8 And that's just a kind of general scientific 9 point, I guess. You know, if you're going to 10 construct an experiment, you've got to have 11 something to compare it to. So that's really the 12 only point that I was trying to make. 13 Q. Why do you need something to 14 compare it to? 15 A. Well, if you're trying to 16 answer a question about whether something exists 17 or doesn't exist, you need to have a comparator, 18 otherwise you won't ever be able to address the 19 question about whether it happened by chance or 20 whether there was really a causal link in your 21 observation. 22 Q. Are you aware that there are 23 statistics that are put out by various 24 governmental agencies and other psychiatric Page 123 1 agencies or schools, et cetera, that speculate or 2 estimate the incidence rate of suicidality in the 3 general population? 4 A. There are such estimates, yes. 5 Q. And generally it's like about 6 fifteen percent, I believe, of depressed patients 7 that actually commit suicide? 8 A. I don't even remember the 9 exact figures. 10 Q. But there are some fairly 11 consistent estimates out there that people have 12 agreed on at various periods of time, correct, 13 like the government -- 14 A. I don't know how much of an 15 agreement there is. It's like all epidemiologic 16 data, there are a lot of -- it's subject to a lot 17 of interpretation. 18 Q. Would you agree that it's 19 generally accepted that there is a percentage of 20 the population of depressed patients that are 21 believed to eventually commit suicide? 22 A. Yes. I mean I don't know that 23 the figure is agreed to in everybody's mind, but 24 in general, depression is believed to be a risk Page 124 1 factor for suicide. 2 Q. And are you aware that the 3 various governmental agencies have put out 4 statistics on suicide rates in a general 5 population, not just depressed patients, but in 6 the general population, for a yearly basis? 7 A. Yes. 8 Q. Every year it changes slightly 9 here and there? 10 A. Yes. 11 Q. Could you then take either one 12 of those populations, either the depressed 13 population or the population in general, and use 14 the percentages that are estimated by, for 15 instance, the government, and I believe that 16 their usual rate is around twelve percent in the 17 general population, could you then pool all the 18 people that you had had in any kind of study 19 whatsoever that you put on Fluoxetine, and look 20 at the rate of suicidality or suicides that 21 occurred within that population to see what the 22 percentage is, would that be a valid comparator? 23 A. It could be done. The 24 validity of such a comparison is really very much Page 125 1 in question, and -- for really many reasons. 2 Q. Why, give me some? 3 A. The patients that are in 4 clinical trials are very closely watched and 5 monitored, they're under active treatment, which 6 patients that aren't -- you know, as you just 7 looked at, some of those may be treated, some of 8 those may not be treated. Certain patients are 9 excluded from clinical trials sometimes, as you 10 pointed out, for various reasons, health reasons, 11 et cetera. So there are many reasons why such a 12 comparison has limited value. 13 Q. Okay. Would the factors, some 14 of the factors that you just set out, like the 15 patients being more closely watched and monitored 16 than the normal general population because of the 17 structure of the clinical trials, and the 18 population being skewed to a certain extent 19 because certain health risks or psychiatric risks 20 are excluded, like serious suicidal risk, would 21 that work in favor of finding the true incidence 22 of suicidality to Fluoxetine or would that skew 23 the population as being less sick to begin with? 24 Do you see what I mean? Page 126 1 A. I understand your question, 2 and the answer is you can't say. There are 3 factors that would lead you to believe that they 4 might have a higher incidence in clinical trials 5 because patients like that were seeking care, you 6 might argue that they would have a lower 7 incidence because certain patients -- well, 8 patients who were under active therapy, and that -- 9 you pointed out exactly the limitation in such 10 comparisons. 11 Q. Could it be that less severely 12 depressed patients were included generally in the 13 clinical trials? 14 A. As I said, it could go either 15 way. You may have even more severely depressed 16 patients because those are the ones that are 17 seeking therapy and identified to participate in 18 the clinical trials. So it could go either way 19 is what I'm saying. 20 Q. Would you consider somebody 21 who is actively suicidal more severely depressed 22 than somebody who is not? And I realize you're 23 not a psychiatrist, you know, but in your 24 opinion. Page 127 1 A. Well, again, I don't know that 2 the data are really very clear in terms of how 3 suicidality links with severity of depression, 4 though there is a high correlation. Patients 5 commit suicide that at least technically aren't 6 clinically depressed. So I don't know, I don't 7 think you can really reach a conclusion about 8 direct correlation between severity of depression 9 and suicidality, it's one component. 10 MS. ZETTLER: Let's break for lunch. 11 (A LUNCH RECESS WAS TAKEN.) 12 Q. Doctor, before lunch we were 13 talking about the German government's package 14 insert that's used with Fluoxetine in Germany. 15 Specifically their suggestion or cautionary 16 statement that in some cases suicidal risk 17 patients you may want to prescribe a concomitant 18 sedative. Do you recall that? 19 A. Yes. 20 Q. Do you personally have a 21 problem with such a statement being added to the 22 United States package insert? 23 MR. MYERS: I object to the form of 24 the question, that's a regulatory issue. Page 128 1 A. Could you -- well -- 2 Q. Let me ask you again. Would 3 you have an objection to the addition of a 4 statement, such as the one in the German package 5 insert, suggesting that there might be a need for 6 a concomitant sedative in patients who are taking 7 Fluoxetine and may be suicidal, being added to 8 the United States package insert? 9 MR. MYERS: Same objection. 10 (DISCUSSION OFF THE RECORD.) 11 MR. MYERS: Do you want him to go 12 ahead and answer or -- 13 MS. ZETTLER: No, he can go ahead and 14 answer. 15 A. I'm sorry, could you repeat 16 the question? 17 MS. ZETTLER: Could you read that 18 back? 19 (THE COURT REPORTER READ BACK THE 20 REQUESTED TESTIMONY.) 21 A. Well, I don't think there's 22 really the need for such a statement as this one, 23 nor do I think there's necessary evidence that 24 suggests that a concomitant addition has been Page 129 1 demonstrated to add significant benefit, or any 2 benefit, concomitant -- the co-administration. 3 Q. Do you know who Doctor Jan 4 Fawcett is? 5 A. I know of -- yes, I know of 6 Doctor Fawcett, yes. 7 Q. Tell me who Doctor Fawcett is. 8 A. I don't know his title, I 9 believe he's -- he's a psychiatrist in Chicago. 10 Q. Okay. Are you aware that 11 Doctor Fawcett has performed clinical trials on 12 Fluoxetine on behalf of Eli Lilly? 13 A. I don't know the specific 14 trials. It wouldn't surprise me if he were an 15 investigator. 16 Q. Do you know that Doctor 17 Fawcett testified at the 1991 advisory committee 18 meeting on behalf of Eli Lilly, and the issue was 19 suicidality and the use of Fluoxetine? 20 A. I didn't remember that he was 21 one of those folks, but -- 22 Q. Do you remember now that he 23 was? 24 A. If you say he was. I don't Page 130 1 remember that he was, but that's fine. 2 Q. Do you know that Doctor 3 Fawcett was at least at one time on Lilly's 4 psychiatric advisory panel? 5 A. I wasn't very involved at all 6 in the psychiatric advisory panel, so I wouldn't 7 have known he was on that. 8 Q. Do you know that Doctor 9 Fawcett was retained or asked as a consultant by 10 Lilly to consult on the issue of suicidality and 11 the use of Fluoxetine? 12 A. If I know there were a group 13 of consultants, and I guess by what you've said, 14 he was one of those. 15 Q. Do you know anybody who was a 16 consultant to Lilly on the issue of suicidality 17 after it was raised by Teicher's article in 1990? 18 A. Well, there were a number of 19 different people who were called in as 20 consultants. Doctor -- well, I guess the answer 21 is yes. 22 Q. Okay, thanks. My follow-up 23 question is why don't you give me some names of 24 those people that you do recall as being Page 131 1 consultants. 2 A. My recollection -- again, 3 these were consultants called in at around that 4 time for suicidality, but they may have been 5 consulting on other issues as well. Doctor 6 Tollefson, I believe Doctor Rush, who was 7 involved in it -- 8 Q. Anybody else? 9 A. I'm sure if I thought long 10 enough, I could reconstruct it, but it's been 11 quite a few years since then. 12 Q. Doctor Winoker? 13 A. Doctor Winoker at what time? 14 Q. After 1990. 15 A. I can't verify for certain, 16 though it wouldn't have surprised me at all 17 obviously if Doctor Winoker would have been 18 called in, I just don't specifically remember 19 whether he was called in again. 20 Q. How about David Dunner? 21 A. I don't believe that Doctor 22 Dunner was specifically called in, but I couldn't 23 be certain that that was the case. 24 Q. Are you aware that Doctor Page 132 1 Dunner, at least at one time, was on Lilly's 2 psychiatric advisory panel? 3 A. As you mentioned it, I think 4 that's correct. 5 Q. Are you aware that Doctor 6 Dunner testified in his deposition that he 7 prescribes in up to fifty percent of his patients 8 on Fluoxetine concomitant sedatives or 9 antidepressants with sedative properties? 10 MR. MYERS: I object to the form, I 11 think you mischaracterized Doctor Dunner's 12 testimony which speaks for itself. 13 MS. ZETTLER: Let's find out exactly 14 what it says, Larry. 15 Q. Doctor are you aware that 16 Doctor Dunner in fact testified at his deposition 17 that Fluoxetine can in fact cause suicidality and 18 violent aggressive behavior? 19 MR. MYERS: Same objection. 20 Q. Were you aware of that? 21 A. I was not aware, I've never 22 seen Doctor Dunner's deposition or any 23 information related to it. 24 (PLAINTIFFS' EXHIBITS 3 AND 4 Page 133 1 WERE MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.). 3 Q. Exhibit 4, for your 4 information, is a compilation of selected pages 5 from Doctor Dunner's deposition. We didn't bring 6 the entire thing because it's rather voluminous, 7 and to make it an exhibit so we could point you 8 to few pages would be a waste of paper. God 9 knows we wasted enough paper in this case. If 10 you'll turn to page eighty-six. Look at line 11 seven, first question is what percentage of your 12 patients would you say have been successfully 13 treated with Fluoxetine. His answer is that's a 14 hard question to answer. Because somebody gets 15 better during treatment, it doesn't mean it's the 16 treatment that got them better, but probably 17 eighty percent of the people they treat get 18 better, okay. Question, out of that eighty 19 percent, how many of those people percent wise 20 have you had to administer concomitant sedatives 21 to, and he asks, including antidepressants, 22 question, sure. Answer, perhaps a third to a 23 half. Do you see that? 24 A. Yes. Page 134 1 Q. Does it surprise you that 2 Doctor Dunner feels that he has to administer 3 concomitant sedatives or antidepressants with 4 Fluoxetine? 5 A. Not the way that this is 6 worded, no. 7 Q. Why? 8 A. Well, specifically he's 9 included other antidepressants as well, and I 10 mean that doesn't surprise me that there would be -- 11 I don't know the percentage, but that there would 12 be some concomitant administration of other 13 antidepressants. It's not a question 14 specifically about sedatives. 15 Q. Well, Doctor, if Doctor Dunner 16 were to feel it necessary to administer a 17 concomitant sedative or antidepressant with 18 sedative properties to his patients on 19 Fluoxetine, would you find that unusual? 20 A. I mean I just don't know, I'm 21 not sure that it's clear enough from the 22 statement. 23 Q. Forget about the deposition 24 now. If that were the case, would you find that Page 135 1 unusual? 2 A. I suppose I would think that 3 fifty percent concomitant administration would be 4 high. 5 Q. Okay. How about twenty 6 percent concomitant sedatives? 7 A. I wouldn't find that as 8 surprising. 9 Q. Why not, why isn't it 10 surprising that twenty percent? 11 A. Well, again, if you're 12 classifying sedatives in other antidepressants -- 13 Q. Other antidepressants with 14 sedative properties. 15 A. Well, maybe you ought to 16 clearly state the question because I think 17 there's some confusion in terms of what's said 18 here and the question you're asking, so maybe 19 just frame the question precisely for me. 20 Q. If Doctor Dunner felt it was 21 necessary in a certain percentage of his patients 22 to co-administer a sedative or low doses of an 23 antidepressant with sedative properties to his 24 patients on Fluoxetine, would you find that Page 136 1 unusual? 2 A. I guess not particularly, not 3 particularly. 4 Q. Why not? 5 A. Well, again, I suppose it's 6 blended into the question because most of the 7 other antidepressants do have some sedative 8 properties. Whether he's chosen those 9 antidepressants for those sedative properties or 10 not, I don't know, so the question is really one 11 of sedatives or other antidepressants, and that 12 kind of falls back to the same answer that I gave 13 before. 14 Q. Is there any reason to 15 co-administer Fluoxetine with another 16 antidepressant? 17 A. Well, there are some 18 situations where physicians have done that in 19 order to enhance efficacy for treatment of the 20 depression. 21 Q. Efficacy of what, Fluoxetine 22 or the other antidepressant? 23 A. Either way I think it's been 24 done. Page 137 1 Q. Why would you want to do that, 2 why would you want to enhance the efficacy of one 3 drug or another? 4 A. You didn't feel you were 5 getting adequate efficacy with the single agent. 6 Q. Is it advisable to 7 co-administer two antidepressants with different 8 properties at the same time? 9 A. Well, again, I said it's been 10 done. I think the preference would be that it 11 not be done, and obviously one has to worry about 12 the drug interactions. But assuming that the 13 physicians were doing that with proper care, it 14 can be done safely. 15 Q. Okay. Turn to page two 16 twenty-three. Do you see towards the middle of 17 the page, line thirteen, question, is it possible 18 that Fluoxetine can cause suicidal ideation, 19 answer, yes. Do you see that? 20 A. Yes. 21 Q. Question, in what cases is it 22 possible. Answer, I don't know. Question, is it 23 possible that Fluoxetine can cause violent and 24 aggressive behavior. Answer, yes. Do you see Page 138 1 that? 2 A. Yes. 3 Q. Does that surprise you that 4 Doctor Dunner would say it's possible that 5 Fluoxetine can cause suicidal ideation and 6 violent aggressive behavior? 7 A. I think it's hard to 8 understand the context in which this was said. 9 It surprises me -- that response does surprise 10 me, but again, I can't say what was going through 11 his mind or what qualifications he may have put 12 on that statement. 13 Q. Let's take the statements as 14 they appear on the page, okay. If that's in fact 15 what he said, which is what is written down here, 16 does that surprise you? 17 A. And I answered that what's 18 written surprises me. 19 Q. Why? 20 A. Because I don't think there's 21 any evidence that what he's saying is true for 22 Fluoxetine anymore than for anything else, any 23 other therapy for depression. 24 Q. Are you saying -- is it your Page 139 1 testimony that you believe that there's no 2 evidence that any antidepressants can cause or 3 exacerbate suicidal ideation? 4 A. The answer to my question -- 5 to your question is that I don't think there's 6 any evidence to suggest that the administration 7 of an antidepressant enhances suicidal ideation, 8 whether it's Fluoxetine or any other 9 antidepressant, any more than any other therapy, 10 that is because depression and suicidal ideation 11 are part of the disease, it's -- there's really 12 no evidence to suggest that such ideation is 13 increased. 14 Q. So you know of no case that 15 suicidal ideation has increased or brought on by 16 the use of an antidepressant, be it Fluoxetine or 17 any other antidepressant? 18 A. I don't believe that's what I 19 said. What I said was that I don't believe 20 there's any evidence that it occurs any more 21 frequently with Fluoxetine than with any other 22 therapy, and that it is part of the disease, so 23 that one may see an increase in suicidality or 24 suicidal ideation during the course of therapy, Page 140 1 that that doesn't confirm that it is related to 2 that therapy, per se. Did I make myself clear? 3 Q. I think you're not really 4 answering my question. You made yourself clear, 5 but I don't think you're answering my question. 6 I'm not concerned about any other therapy other 7 than antidepressants. 8 A. Right. 9 Q. Is it your opinion that 10 there's no evidence that any antidepressant, in 11 and of itself, can cause suicidal ideation or 12 exacerbate suicidal ideation? 13 MR. MYERS: I object to the question, 14 it's been asked and answered. 15 MS. ZETTLER: No, it hasn't. 16 A. Well, again, I think it has 17 been answered. I said I don't think there is 18 evidence that Fluoxetine or any other 19 antidepressant cause suicidal ideation. 20 Q. Okay. 21 A. In my opinion. 22 Q. Based on what? 23 A. Based on the fairly 24 comprehensive data review that was done as part Page 141 1 of the review when this issue came up in 1990. 2 Q. You reviewed evidence on every 3 single antidepressant on the market at that time? 4 A. No. 5 Q. You reviewed evidence on 6 Fluoxetine, correct? 7 A. Well, Fluoxetine, and there 8 were comparator drugs in the Fluoxetine data 9 base. 10 Q. Okay. Isn't it true that the 11 data that you presented at the 1991 -- when I say 12 you, I mean Lilly in general -- at the 1991 13 advisory committee meeting showed a lower 14 incidence across the board, regardless of 15 treatment, Imipramine, Fluoxetine, placebo, than 16 is normally found within the depressed 17 population? 18 A. Yes. 19 Q. Across the board? 20 A. Than are commonly believed, 21 incidence of suicide, suicidal ideation. 22 Q. Quite a bit lower? 23 A. I don't remember the 24 magnitude, but it was lower, yes. Page 142 1 Q. Less than half the percentage 2 that is commonly believed to occur in the 3 depressed population, correct? 4 A. I don't know -- again, I don't 5 know the percentages, I wouldn't want to be 6 quoted. 7 Q. Don't you think that's 8 unusual? 9 A. Well, again, one has to 10 understand the course of care in a clinical trial 11 and the fact that they are under treatment, and 12 that in the general population not all of those 13 patients may be under treatment. So I think 14 there are lots of explanations in why that could 15 occur. 16 Q. Another factor is therapy 17 monitored far more closely than most people are 18 in the general public that are being treated with 19 antidepressants, correct? 20 A. As part of the clinical trial, 21 they would be monitored very closely. 22 Q. A lot of the clinical trials 23 allowed for the co-administration of sedatives 24 and hypnotics and benzodiazepines within the Page 143 1 clinical trials, did they not? 2 A. Yes. 3 Q. In your opinion would that 4 serve to mask in a lot of cases the potential 5 stimulant profile, adverse event profile, of 6 Fluoxetine? 7 A. I don't believe that there was 8 ever -- that was evaluated, and I don't believe 9 there was any evidence that that was the case, 10 that -- but that's, you know, remote 11 recollection. 12 Q. So you were in fact doing to a 13 certain extent what Doctor Dunner testified in 14 this deposition he does in his practice during 15 the clinical trials, were you not? 16 A. I don't think -- I don't 17 recall the frequency, but I don't believe that it 18 was nearly as high as what he suggested. 19 Q. I'm not talking percentage 20 wise, I mean he was in effect doing what was 21 being done during the clinical trials with his 22 patients, was he not, co-administering sedatives 23 or drugs with sedative properties? 24 A. Again, I don't know enough Page 144 1 about what he's saying, so I think it's really -- 2 I can't confirm that that was the case. There 3 were concomitant administration of some sedatives 4 for sleep, primarily, during the course of the 5 clinical trials. The frequency, I don't know, 6 but it wasn't very high as I recall. 7 Q. What was done to evaluate 8 whether or not the concomitant administration of 9 sedatives and hypnotics and benzodiazepines 10 during the clinical trials had any effect on the 11 side effect profile of Fluoxetine as it showed in 12 the clinical trials? 13 A. I don't remember the details 14 of the analysis done at that time. 15 Q. Was that information presented 16 at the 1991 advisory committee meeting? 17 A. Which information? 18 Q. On what was done to evaluate 19 whether or not the co-administration of those 20 other psychotropic drugs had any effect on the 21 evaluation of Fluoxetine's true side effect 22 profile? 23 A. To my knowledge, that was not 24 presented. Page 145 1 Q. Do you know why not? 2 A. I really don't know why not. 3 I imagine because it was really a negative 4 finding, but that's speculation. 5 Q. Was the fact that the German 6 government raised the issue of suicidality and 7 the use of Fluoxetine discussed at the committee 8 meeting in 1991? 9 A. Which committee meeting are 10 you referring to? 11 Q. The advisory committee 12 meeting. 13 A. I don't remember the German 14 situation being discussed at that time. 15 Q. There were analyses done of 16 the data bases that existed in '84, and later in 17 response to the German questions on suicidality, 18 were there not? 19 A. I'm sorry, could you repeat 20 the question again? 21 Q. Sure. You guys did an 22 analysis of the data bases that existed at the 23 time in response to the German government's 24 questions regarding suicidality and the use of Page 146 1 Fluoxetine, correct? 2 A. Yes. 3 Q. Were those analyses reduced to 4 writing for submission to the BGA? 5 A. I believe they were in 6 response to their questions. 7 Q. Okay. Wouldn't those analyses 8 have been useful or relevant, to use your word, 9 to the 1991 advisory committee? 10 A. Well, the analysis -- there 11 are a couple of things. One is the data would 12 have been submitted to the FDA. I mean I 13 personally can't confirm that, but again, 14 standard policy would be that all analyses that 15 were submitted to the BGA would also have been 16 submitted to the FDA. So there's never any 17 question that the FDA knew about that. The 18 second point is that the data that was submitted 19 to the BGA would have been dated at that time 20 because there was a much larger data base from 21 which to draw that information. So a very 22 similar analysis would have been done on the 23 larger population at the time of the FDA review. 24 So I'm not sure that the German data would have Page 147 1 been terribly relevant, it was included in a 2 larger data base. 3 Q. So it's your belief that the 4 FDA knew about the German government's questions 5 regarding suicidality and the use of Fluoxetine? 6 A. It's my belief the FDA knew 7 about that. 8 Q. When would they have known 9 about it? 10 A. They would have known about it 11 close to the time that it occurred in Germany. 12 In other words, when that report came, it would 13 have been standard procedure at the next update 14 of the file to have provided that information to 15 the FDA. 16 Q. Is it your belief that that 17 information was provided to the FDA before it 18 approved Prozac for marketing here in the United 19 States? 20 A. Again, I can't personally 21 confirm that, but it would be my belief that it 22 would have been provided prior to approval in the 23 U.S. 24 Q. Can you conceive of any reason Page 148 1 whatsoever why Lilly would have not submitted 2 that analysis to the FDA? 3 A. I don't know of any reason why 4 they wouldn't have submitted it. 5 Q. To your knowledge is there my 6 regulatory reason or other reason dictated by the 7 FDA why Lilly couldn't have added the sedative 8 cautionary statement in the German package insert 9 to the United States package insert? 10 A. Well, again, I think that's a 11 regulatory question. There's a conceivable 12 reason why they would not have allowed us to add 13 it, and that is that you are suggesting the use 14 of another medication, the efficacy which has not 15 been confirmed. And there have been situations 16 that we have in fact not been allowed to say 17 things very similar to what was said in the U.S. 18 package insert. 19 Q. You were doing it in your 20 clinical trials, weren't you? How could you say 21 that the efficacy was not being confirmed if you 22 were administering sedatives and hypnotics during 23 your clinical trials? 24 A. The clinical trials are in Page 149 1 fact evaluations of those medications. What 2 you're saying in the package insert is that this 3 co-administration has been shown to be safe and 4 effective. And the FDA, I can't say uniformly, 5 but they will object to the suggestion of 6 co-administration of drugs if they have not been 7 shown to be safe and effective. 8 Q. Could you have added a 9 statement to the U.S. package insert that 10 Fluoxetine is not sedating? 11 A. Probably not. 12 Q. Why not? 13 A. Because I think the FDA -- 14 again, you're asking me to sit in the chair of 15 the regulator, and the way I understand the 16 question, you're saying is it conceivable, and 17 I'm saying yes, it is conceivable, just to 18 clarify that, because the FDA might feel that. 19 Again, we're making a claim for Fluoxetine that 20 it is not sedating, and as you've mentioned 21 before, there are some patients in which sedation 22 does occur. It would be a product advantage 23 claim, and they wouldn't allow us to say that. 24 Q. Are you aware that Doctor Page 150 1 Beasley conducted an analysis of data collected 2 by Lilly during clinical trials that showed at 3 least in his opinion that there was a trend that 4 Fluoxetine could be activating in patients 5 suffering from agitated depression? 6 A. I don't know which analysis 7 you're referring to from Doctor Beasley. 8 Q. So you're saying you're not 9 aware of that study? 10 A. I'm not aware of the study. 11 Q. Okay. If Lilly went to the 12 FDA and said we have found evidence that this 13 drug is activating in a certain percentage of 14 people, we would like to put something in the 15 package insert informing the physicians about 16 what we have found, is it your belief that the 17 FDA would not have allowed you to do that? 18 A. Again, it's very difficult to 19 predict what the FDA would allow you to and would 20 not allow you to do, I really couldn't predict 21 what the FDA would have said in that situation. 22 Q. So it's your testimony if the 23 sponsor of a drug goes to the FDA and informs 24 them of a potential side effect profile for the Page 151 1 drug, that the FDA would possibly not allow the 2 company to include information about that side 3 effect profile in the package insert? 4 A. The -- it's possible, it is 5 possible, depending upon the wording involved. 6 Q. Besides the semantics of the 7 wording involved, are you saying that the FDA 8 would -- it's possible that the FDA would not 9 allow the drug company to inform the prescribing 10 physician of side effect profiles of a drug that 11 it's marketing? 12 A. Again, you can't ignore the 13 wording involved because the wording is very 14 important. The company can implement changes, 15 the FDA can object to those changes, and it 16 depends, they may object based on the words that 17 you chose -- how you chose to describe it. Your 18 example is a very good one about non-sedating. 19 Q. Could the company go to the 20 FDA and say, for example, we have found in fifty 21 percent of the patients that have been 22 administered Fluoxetine that it acts as an 23 activating drug? 24 A. Could you repeat the question? Page 152 1 MS. ZETTLER: Could you read it back? 2 (THE COURT REPORTER READ BACK THE 3 REQUESTED TESTIMONY.) 4 A. Well, the company certainly 5 could go to the FDA making those statements. 6 Q. I'm just trying to understand 7 your testimony, Doctor, because frankly it's kind 8 of astounding to me, but is it your testimony 9 that if the FDA didn't agree with a particular 10 language you wanted to use to inform the 11 physicians of your findings, that they would not 12 allow you to inform the physicians at all or you 13 would have to negotiate the language that would 14 be used? 15 A. Well, I'm saying there are 16 situations in which the FDA has refused to allow 17 us to put information in the label related to the 18 specifics of a therapeutic intervention with the 19 drug. 20 Q. Has that ever happened with 21 Fluoxetine? 22 A. Yes. 23 Q. Okay. Give me an example of 24 where that's happened with Fluoxetine. Page 153 1 A. In the situation with MAOI 2 inhibitors, we proposed at one point to the FDA 3 that wording be placed as to advice on how to 4 treat patients if this occurred, and the FDA 5 would not allow us to put that in because it made 6 a claim for those medications which was not 7 proven, it was only anecdotal. 8 Q. But it didn't prevent you from 9 putting a warning or contraindication statement 10 in the package insert informing the physician 11 that you shouldn't use MAO inhibitors in 12 conjunction with Fluoxetine or within a certain 13 period of time within each other, right? 14 A. That was done, that already 15 existed in the label. But your question was, as 16 I understood it, was had the FDA refused to let 17 us put things in that we felt informed the 18 physicians about care of the patients from a 19 safety standpoint. 20 Q. No, that's not my question at 21 all. 22 A. Well, that's the question I 23 answered. 24 Q. My question, Doctor, is it Page 154 1 your testimony that the FDA -- and I'm not 2 talking about treatment of an adverse event, I'm 3 talking about an adverse event profile itself, 4 okay, a side effect profile. Say it started 5 making people have high blood pressure, okay, 6 some people had high -- you found in ten percent 7 of the patients that you gave it to, their blood 8 pressure was increased, they became hypertensive 9 or whatever, okay. Are you saying that if you 10 went to the FDA a and said look, we've been doing 11 these studies and we're starting to find that in 12 ten percent of the patients hypertension is 13 occurring and we would like to add something to 14 the package insert to inform the prescribing 15 physician of that, are you saying that they are 16 going to say no, you can't do that? 17 A. Well, in that situation, I 18 think they would almost certainly say yes. 19 Q. Okay. What about if you were 20 to go to them and say look, the German government 21 has analyzed the data that we provided to it and 22 has found that Fluoxetine is not sedating, and 23 has suggested in their package insert that we 24 include a recommendation that in some cases Page 155 1 people who pose a suicide risk are going to have 2 to have concomitant sedatives, we would like to 3 do that in the package insert here in the United 4 States. What do you think they would say in that 5 case? 6 A. I think it's very questionable 7 that they would let you add that to the U.S. 8 label. 9 Q. Why? 10 A. For the reasons that I've 11 already cited, which is it recommends a 12 concomitant medication for which there has been 13 no proof of efficacy. 14 Q. What about adding a simple 15 statement that Prozac is more activating than it 16 is sedating? 17 A. Well, I mean, again, it's very 18 difficult for me to speculate. I don't believe, 19 though, that having dealt with the FDA that even 20 that kind of statement would be a simple yes 21 answer, there would likely be much negotiation 22 about exactly what the wording would be so that 23 it conveyed an accurate picture of what the best 24 evidence suggested. Page 156 1 Q. Regardless of what the wording 2 is, is it your testimony that the FDA -- or is it 3 possible that the FDA would not allow you to put 4 anything in the package insert related to some 5 people experiencing activation on the drug? 6 A. Well, again, if there were 7 evidence to support that point, the FDA would 8 allow us to put it in, in my opinion. 9 Q. Okay. If Doctor Beasley had, 10 or somebody on behalf of Lilly had gone to the 11 FDA with the results of Doctor Beasley's analysis 12 regarding activation and sedation, would they 13 have allowed the results to be paraphrased or put 14 into the package insert in some way? 15 A. I would say that the FDA, 16 again, would look at the breadth of evidence, not 17 any single study, single observation or even 18 single recommendation by another regulatory 19 authority before they would reach the conclusion 20 that that wording should be placed in the package 21 insert. 22 Q. I'm talking about Doctor 23 Beasley's study. 24 A. And I'm making the Page 157 1 generalization from Doctor Beasley -- Doctor 2 Beasley -- I don't even know what Doctor 3 Beasley's study information was, but I don't 4 believe that they would simply take a single 5 piece of information, without considering that, 6 with the whole breadth of data, before they would 7 reach the conclusion, unless it were an 8 immediately life-threatening issue like the MAOI 9 interaction data. 10 Q. Isn't it true that the FDA 11 asked Lilly to put information about MAO 12 inhibitors in the contraindication section of the 13 label after a few people had died as a result of 14 interaction between MAO inhibitors and 15 Fluoxetine? 16 A. I don't know the sequence of 17 events, exactly who asked who, but my 18 recollection is that Lilly was the initiator of 19 those changes with regard to MAOI inhibitors, not 20 the FDA. 21 Q. When you say the initiator of 22 the changes, do you mean placing information in 23 the package insert dealing with MAO inhibitors at 24 all or the location of the information? Page 158 1 A. I'm talking about the 2 initiation to put it into the label. I don't 3 recall the negotiations about exactly where in 4 the label it was to have been put. 5 Q. To your knowledge was that the -- 6 was the first time that information about the 7 interaction between MAO inhibitors and Fluoxetine 8 in the original package insert? 9 A. I'm sorry, you'll have to 10 repeat that question. 11 Q. Was the MAO inhibitor 12 interaction information, okay -- 13 A. Yes. 14 Q. -- was that in the original 15 package insert for Fluoxetine or did it come in 16 at a later date? 17 A. I believe it came in at a 18 later date. 19 Q. Do you remember when? 20 A. I don't. I think I was out of 21 the country at that time. It was not long after 22 approval, as I recall. 23 Q. Were you out of the country at 24 the time of approval? Page 159 1 A. Yes. 2 Q. Besides Doctor Montgomery's 3 risk study of Fluoxetine in suicidal patients, 4 are you aware of any other studies done by Lilly 5 or on behalf of Lilly where the issue of 6 suicidality and the use of Fluoxetine was 7 studied? 8 A. Well -- 9 Q. Before or after 1990. 10 A. It depends how you 11 characterize a study. There was a very extensive 12 analysis of the pooled data to address the 13 question of suicidality, and there was a very 14 extensive evaluation of spontaneous events and 15 suicidality. Both those could be considered 16 studies. 17 Q. So you're talking about Doctor 18 Beasley's meta-analysis as one? 19 A. Yes, yes. 20 Q. And -- 21 A. It was Doctor Beasley and many 22 others, but -- 23 Q. The one that appeared in the 24 British Medical Journal? Page 160 1 A. Yes. 2 Q. Is that different than the 3 evaluation of the spontaneous events or was that 4 the evaluation of the spontaneous events reported 5 in Doctor Beasley's article? 6 A. No. Doctor Beasley's article 7 only, I think, addressed the controlled clinical 8 trials. 9 Q. Okay. All controlled clinical 10 trials? 11 A. All controlled clinical trials 12 that could be pooled scientifically, that had 13 similar enough data that you could actually come 14 up with a reasonably scientific hypothesis and a 15 reasonable answer to that question. 16 Q. To your knowledge did Doctor 17 Beasley include the clinical trials conducted 18 outside the United States in his meta-analysis? 19 A. In the initial meta-analysis, 20 the data outside the U.S. were not included. 21 However, the data outside the U.S. were included 22 in the later similar analysis. 23 Q. The BMJ article, did that 24 include the outside U.S. data? Page 161 1 A. I don't believe it did. 2 Q. And the OUS data analysis, was 3 that ever published? 4 A. I don't know, I don't think it 5 was. 6 Q. The OUS data analysis was done 7 for the 1991 advisory committee, was it not? 8 A. I can't recall whether the OUS 9 analysis was done at the time of the advisory 10 committee or not. I believe it was, but I 11 couldn't be certain. 12 Q. Are you aware of any analyses 13 that were done after the advisory committee in 14 1991? 15 A. I don't know of any specific 16 analyses done after the advisory committee. 17 MS. ZETTLER: Let's take a break. 18 (A SHORT RECESS WAS TAKEN.) 19 Q. What is Hoechst? 20 A. Hoechst is a pharmaceutical 21 company, I think it's a big chemical 22 pharmaceutical company. 23 Q. Are they related in any way to 24 Lilly? Page 162 1 A. I don't believe there are any 2 direct commercial ones. 3 Q. Have they ever acted as a 4 distributor for Lilly, of its products in 5 Germany? 6 A. I don't know for certain that 7 they've acted as a, quote, distributor, per se. 8 (PLAINTIFFS' EXHIBIT NO. 5 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. Have you had at chance to 12 review Exhibit 5? 13 A. Yes. 14 Q. Do you recognize that exhibit? 15 A. I don't. 16 Q. Do you recall attending a 17 meeting with Hoechst representatives on April 11, 18 1990? 19 A. I don't remember it. 20 Q. Do you ever recall attending 21 any meetings with Hoechst representatives? 22 A. I don't recall ever attending 23 a meeting with Hoechst. 24 Q. Do you have any reason to Page 163 1 believe that you did not attend the meeting as 2 listed on this exhibit? 3 A. There's no reason to believe I 4 didn't attend it if it said that I did. 5 Q. Okay. And it's your 6 understanding that there was no commercial 7 relationship between Hoechst and Lilly, correct? 8 A. That's not true, I mean 9 Hoechst was, I think, at one point, a 10 co-marketer. I thought you asked specifically 11 about distribution, and I don't know whether they 12 were involved in distribution, but I think they 13 were a co-marketer of -- 14 Q. What's a co-marketer? 15 A. Somebody that -- it's either 16 co-marketer or co-promoter, and the difference is -- 17 well, I probably shouldn't get into the business 18 terms, but basically we worked together in the 19 promotion of Hoechst in Germany at one point. 20 Q. And did Hoechst promote or 21 market Fluctin or Fluoxetine in Germany at one 22 point? 23 A. I think they co-marketed 24 Fluctin in Germany. Whether it was called Page 164 1 Fluctin or not, I don't know, Fluoxetine. 2 Q. This appears to be a draft of 3 meeting minutes from a meeting held between 4 various Lilly employees and representatives from 5 Hoechst, right? 6 A. That's what it would appear to 7 be. 8 Q. And it says on Points of 9 Agreement: Sharing of Safety Data, do you see 10 that? 11 A. Yes. 12 Q. Okay. Set-up systems with 13 Lilly Germany, correct? 14 A. Yes. 15 Q. Do you recall that happening? 16 A. There was a great deal of 17 discussion about being insured that the data from 18 the Hoechst sales representatives in fact was 19 captured in the world-wide data base on 20 Fluoxetine to be certain that that happened. So 21 that may have been the -- what this is referring 22 to. 23 Q. Did you find any differences 24 between what was reported to, say, the German Page 165 1 government with regards to the safety of the drug 2 and what was reported to the FDA? 3 A. I'm sorry, can you be more 4 specific about what you mean in asking that 5 question because it could be interpreted in a 6 wide variety of ways. Can you be more specific? 7 Q. Was there any information 8 regarding the safety of Fluoxetine that was 9 provided to the BGA that was not provided to the 10 FDA or vice-versa? 11 A. Our standard policy would be 12 to see that all governments got the same 13 information, all government regulators got the 14 same information unless they specifically 15 requested that they not receive certain types of 16 information. 17 Q. Do you ever recall the BGA 18 requesting that they not be given certain types 19 of information with regards to safety of Prozac? 20 A. I can't say specifically about 21 Germany, but there were countries in Europe that 22 did not want to receive our routine printout of 23 adverse events. Now I don't know whether Germany 24 was one of those or not. Page 166 1 Q. Okay. Look at the bottom of 2 the page, it says in addition it was suggested 3 that they be sent. Do you see that? 4 A. Yes. 5 Q. Summary basis of approval, 6 1987, correct? 7 A. Yes. 8 Q. Advisory committee review 9 minutes, 1985, correct? 10 A. Yes. 11 Q. Everything in DEN for Prozac 12 on disks. Do you see that? 13 A. Yes. 14 Q. And weekly CIOM reports, 15 correct? 16 A. Yes. 17 Q. Do you recall Hoechst being 18 provided everything in the DEN for Prozac on a 19 disk? 20 A. I don't recall specifically 21 that it happened, but I have every reason to 22 believe that we provided the information. It may 23 or may not have been on disks, but we would have 24 provided any and all information on safety to Page 167 1 Hoechst that they requested. 2 Q. Do you recall providing any 3 other entity or Lilly providing any other entity 4 with information from the DEN data base besides 5 the FDA? 6 A. I'm sorry, reread the question 7 again. 8 Q. Let me ask it again. Besides 9 the 1639s or other information that was provided 10 to the FDA that was either stored in the DEN data 11 base or was generated as a result of the DEN data 12 base, do you recall any other entity or person 13 ever being given information such as what's 14 listed here, everything in the DEN for Prozac, 15 transferring that information in any way? 16 A. I'm going to have to ask you 17 to ask the question again, I'm sorry, I still 18 don't understand. 19 Q. Let me ask it this way: Have 20 you ever seen the DEN data base being transferred 21 to anyone on a disk or on disks? 22 A. I can't say that I've ever 23 seen anybody transfer it on disks. 24 Q. Okay. Have you ever accessed Page 168 1 the DEN data base yourself? 2 A. I don't recall ever accessing 3 it myself. 4 Q. If you wanted information from 5 the DEN, how would you get it? 6 A. I would have gone to the 7 regulatory group in Indianapolis. 8 Q. Did Doctor Max Talbott ever 9 work under your supervision? 10 A. Yes. 11 Q. When? 12 A. When I -- he was -- from the 13 time that I was -- I came back to Indianapolis in 14 1990, I think until I left Lilly, Max reported to 15 me in one fashion or another. I believe that's 16 true, it's hard to go through with the 17 organizational changes, but in general, that was 18 true. 19 Q. Okay. Go back towards the 20 middle of the page under the section that says To 21 be Explored. 22 A. Yes. 23 Q. At the bottom, it says 24 Suicidality update. Do you see that? Page 169 1 A. Right. 2 Q. Is this meeting related to 3 marketing of Fluoxetine in Germany to your 4 knowledge? 5 A. Again, I don't recall the 6 meeting, and it's really -- I could only 7 speculate at what stage in the commercial 8 arrangement with Hoechst this occurred, I really 9 don't know. 10 Q. Would Hoechst be working with 11 Lilly to market the drug in any other country 12 besides Germany? 13 A. I don't believe so. 14 Q. Do you have any idea what 15 they're talking about here when they say 16 suicidality update? 17 A. Again, I can only speculate. 18 My speculation would be that this is related to 19 the activity at the time, around April, 1990. 20 And it was really more a U.S. issue at that 21 point. That's what I would guess it's saying or 22 asking for. 23 Q. Have you ever heard of Doctor 24 Mobius or Mobius, M-O-B-I-U-S? Page 170 1 A. I have heard of Doctor Mobius. 2 Q. Who is Doctor Mobius? 3 A. He's a German physician who 4 has taken anti-industry stands, I guess would be 5 a fair way to summarize it, in the past. 6 Q. Is he a governmental official? 7 A. I don't believe he is a 8 government official. 9 Q. Would it be fair to say that 10 Doctor Mobius was kind of like the Ralph Nader of 11 Germany? 12 A. It's more -- I would have 13 thought more like the Sidney Wolf of Germany. 14 (PLAINTIFFS' EXHIBIT NO. 6 WAS 15 MARKED FOR IDENTIFICATION AND 16 RECEIVED IN EVIDENCE.) 17 Q. Have you had a chance to 18 review Exhibit 6? 19 A. Yes. 20 Q. Do you recognize that exhibit? 21 A. I don't. 22 Q. Are you aware that Doctor 23 Mobius has published that letter in, looks like, 24 early 1990? Page 171 1 A. I know that there was a lot of 2 activity on the part of Doctor Mobius' part in 3 relation to Fluctin, but I was not -- I can't say 4 that I would recognize the letter, per se. 5 Q. What kind of activities was 6 Doctor Mobius engaging himself in with regards to 7 Fluctin? 8 A. I don't know the specific 9 activities. I know there were just -- there was 10 a lot of noise on his behalf, but I don't know 11 exactly what he was doing, who he was contacting 12 and so forth. 13 Q. To your knowledge did Doctor 14 Mobius ever consult with the BGA on the issue of 15 Fluoxetine? 16 A. I don't know that he did or 17 didn't. 18 Q. Since that's the only copy 19 that I have, I think I'll look over your 20 shoulder. Who is S. von Oesterreich? 21 A. I think she was -- well, I'm 22 not -- she was a member of the Lilly staff in 23 Germany. 24 Q. Okay. Do you recall what her Page 172 1 position was? 2 A. I don't recall what her 3 position was at that particular time. 4 Q. Who is Ed? 5 A. I can only speculate, I don't 6 know who Ed would be. 7 Q. Ed West? 8 A. It could be. 9 Q. In the last page of the 10 Exhibit, Doctor Mobius' conclusion is set out, 11 correct? 12 A. Yes. 13 Q. This article is about the 14 imminent launch of Fluoxetine in Germany, right? 15 A. I don't know. 16 Q. The first line of the article 17 says Fluoxetine is intended for marketing in the 18 Federal Republic of Germany by Hoechst A.G., and 19 is already being marketed in the U.S. under the 20 product name Prozac by Lilly, correct? 21 A. That's what it says, yes. 22 Q. So he at least feels that 23 Lilly and Hoechst want to market it in Germany at 24 this time, right? Page 173 1 A. It's intended for marketing, 2 that's what it says, yes. 3 Q. His conclusion after 4 discussing various aspects of -- at least his 5 opinion with the drug is that Fluoxetine is not 6 more effective than conventional tricyclic 7 antidepressants, but has a wider margin of 8 serious adverse effects with immunoallergic 9 reactions and stimulating effects such as the, 10 quote, serotonin syndrome, unquote, correct? 11 A. That's what it says, yes. 12 Q. Have you ever heard of the 13 serotonin syndrome before? 14 A. Yes. 15 Q. What is serotonin syndrome? 16 A. He describes what the 17 serotonin syndrome, quote, serotonin syndrome, 18 unquote, is in here. I think it's used by 19 different people in different ways. 20 Q. Okay. What is Doctor Mobius' 21 description of a serotonin syndrome? 22 A. If I can find it here. I 23 can't find it at the moment, I'm sorry -- okay, 24 headache, twenty-one percent, nervousness, Page 174 1 fifteen percent, insomnia, fourteen percent, 2 drowsiness, twelve percent, anxiety, nine 3 percent, tremor, eight percent, gastrointestinal 4 disorders such as vomiting, twenty-five percent. 5 Q. And it goes on to say paranoid 6 and panic reactions occur as well as mania, 7 psychosis and extrapyramidal symptoms, right? 8 A. That's right. 9 Q. Effects untypical of 10 antidepressants is what he concludes there, 11 correct? 12 A. These are his conclusions. 13 Q. Do you agree with him that 14 paranoid and panic reactions, mania, psychosis, 15 and extrapyramidal symptoms are untypical of 16 antidepressants? 17 A. Well, they're untypical of all 18 antidepressants, including Prozac, untypical. 19 Q. Untypical. 20 A. Untypical, yes. 21 Q. Do you think that anybody who 22 has taken Prozac and has suffered from paranoid 23 and panic reactions, mania, psychosis or 24 extrapyramidal symptoms? Page 175 1 A. There are patients who while 2 taking Prozac have those kinds of reactions or 3 these kinds of symptoms, however there are 4 patients that on other antidepressants that also 5 have these kinds of symptoms. 6 Q. Are you saying that it's 7 inconceivable that somebody on Fluoxetine can 8 become paranoid because of the Fluoxetine, as a 9 reaction to the Fluoxetine? 10 A. In my opinion the relationship 11 of Fluoxetine to paranoia is very unlikely. 12 Q. Why? 13 A. Because a much more plausible 14 explanation is that it's related to the 15 underlying disease being treated. 16 Q. What about garden variety 17 depression? 18 MR. MYERS: What about it? 19 Q. Is paranoia related to the 20 underlying disease of depression, without any 21 schizophrenia or any other related element? 22 A. I think there's a wide variety 23 of disorders that are kind of pooled into the 24 category of depression, and paranoia in some of Page 176 1 those situations. 2 Q. Let's use the DSM3R 3 description of depression, major depressive 4 disorder, okay, can you do that? 5 A. Well, again, I think you're at 6 risk of comparing apples and oranges a little bit 7 if you restrict me to the DSM3. 8 Q. I'm asking you a specific 9 question. Restrict yourself to the DSM3 10 definition of major depressive disorder, okay. 11 In those patients is it typical for a patient to 12 become paranoid? 13 A. I would have to refer to DSM3 14 to find out exactly whether paranoia is listed as 15 one. 16 Q. Is it typical for somebody who 17 is suffering from depression, according to the 18 criteria set out in DSM3, to suffer psychosis? 19 A. I don't believe it's typical, 20 but it doesn't mean that it couldn't happen. 21 Q. Okay. People suffering from 22 these various things that Doctor Mobius lists 23 here, like paranoia, mania, psychosis or 24 extrapyramidal symptoms, were excluded from the Page 177 1 clinical trials on Fluoxetine, were they not, at 2 least the majority of the clinical trials? 3 A. Yes, I think it's fair to say 4 that they were excluded from the majority of 5 clinical trials. 6 Q. Bi-polar, people suffering 7 from bi-polar disorders were generally excluded 8 from the clinical trials also, weren't they? 9 A. They were excluded from most 10 clinical trials, yes. 11 Q. Let's go back to suicide 12 studies that have been conducted by Lilly or 13 anybody on behalf of Lilly. Other than the 14 evaluations done by Lilly of the pre-existing 15 data, okay, are you aware of any studies that 16 were conducted, and we can start with 17 double-blind controlled clinical trials if you 18 want, to study the issue of suicidality and the 19 use of Fluoxetine? 20 A. Again, could you clarify for 21 me the time frame you're talking about? 22 Q. Anytime, anytime whatsoever, 23 before or after 1990 when the issue was raised by 24 Doctor Teicher's article. Page 178 1 A. Other than -- again, which 2 studies are you including in the ones that I'm 3 not to consider? 4 Q. The ones -- the reevaluations 5 of pre-existing data that were done by Doctor 6 Beasley and his colleagues in response to the 7 Teicher article. 8 A. Well, I think I also mentioned 9 the study that Doctor Montgomery did. 10 Q. Right. Besides that. 11 A. There was also the 12 incorporation of another scale in clinical trials 13 following the identification of that scale, and 14 once we were -- well, after identification of 15 that scale. 16 Q. Are you taking about Ivan 17 Miller's scale? 18 A. Well, I'm not sure, I can't 19 remember who the originator of the scale was. 20 Q. The scale that was developed 21 in part by Lilly with the cooperation of somebody 22 from outside Lilly? 23 A. Again, I'm sorry, I can't 24 confirm it was Ivan Miller's scale. I know that Page 179 1 Ivan Miller was involved, but I don't know 2 whether that was the one that was incorporated or 3 whether that was the one that was in development. 4 Q. Okay. So there was one in 5 development and there was another one that was 6 actually incorporated, correct? 7 A. That's my recollection, yes. 8 Q. If I were to tell you that 9 recently through other deposition testimony it 10 was established that the scale that was actually 11 incorporated was the adult suicidal ideation 12 questionnaire, would that refresh your 13 recollection as to whether or not that was Doctor 14 Miller's scale? 15 A. That would not help me I'm 16 afraid. 17 Q. Okay. Are you aware that 18 Doctor Miller conducted a study to validate his 19 scale? 20 A. I can't -- I don't know the 21 specifics of such a study. I would expect that 22 Doctor Miller would have validated his scale. 23 Q. You're not aware of a study 24 that was being conducted -- Page 180 1 A. I'm not aware of a specific 2 study. 3 Q. Are you aware of any 4 suicidality studies that Catherine Mesner was 5 working on? 6 A. No. 7 Q. Okay. Other than the studies 8 that we've already talked about, are you aware of 9 any study that was planned, developed or 10 conducted by Lilly and/or on behalf of Lilly to 11 look at the issue of whether or not people who 12 are taking Fluoxetine become suicidal or their 13 suicidality is exacerbated because of the 14 Fluoxetine? 15 A. I think all of those studies 16 have been cited. 17 Q. Okay. How about violent 18 aggressive behavior, are you aware of any study, 19 and I'm not talking about a reanalysis of 20 pre-existing data, because I know Doctor 21 Heiligenstein did that and published a paper with 22 a bunch of other authors, I'm talking about a 23 clinical trial or other study that was 24 specifically conducted with the objective of Page 181 1 studying or investigating the occurrence of 2 violent aggressive behavior and the use of 3 Fluoxetine? 4 A. To my knowledge, there were no 5 prospective studies of violent or aggressive 6 behavior. 7 Q. Okay. Why not? 8 A. Let me -- again, it vaguely 9 runs in my mind there may have been a trial in 10 adolescents that may have had some aggressive 11 behavior, but that's speculation. 12 Q. Before or after 1990? 13 A. I think it may have been after 14 1990. 15 Q. Okay. 16 A. But that's probably not fair 17 because I can't remember the details of that. 18 Q. Do you recall if it was a 19 study where the objective was to look at the 20 incidence of violent aggressive behavior on 21 adolescents using Fluoxetine or if the result of 22 that study was that adolescents in the study 23 became violent aggressive when they were on 24 Fluoxetine? Page 182 1 A. No, it was not the latter, it 2 was the former. 3 (PLAINTIFFS' EXHIBIT NO. 7 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to 7 review Exhibit 7? 8 A. Yes. 9 Q. Do you recognize Exhibit 7? 10 A. I don't recognize it. 11 Q. Do you recall being on the 12 Clinical Research Grants Committee? 13 A. Yes. 14 Q. In 19 -- September of 1991? 15 A. Yes. 16 Q. Okay. Look towards the bottom 17 of the page, it lists a bunch of items under the 18 initial grant category. Do you see that? 19 A. Yes. 20 Q. Item two says Butler Hospital, 21 Fluoxetine S002, S001, and HCFQ. Do you see 22 that? 23 A. Yes. 24 Q. Do you know what any of those Page 183 1 studies are, S002, S001, and HCFQ? 2 A. I don't. 3 Q. What about Butler Hospital, 4 where is Butler Hospital? 5 A. I don't know. 6 Q. How about item three, Ivan 7 Miller, Ph.D, and it's got the same studies 8 listed, Fluoxetine S002, S001, and HCFQ. Do you 9 see that? 10 A. Yes. 11 Q. Do you know anything about 12 that? 13 A. I mean, the name Ivan Miller 14 is a familiar name, but other than that, I can't 15 recognize any of these protocols by their codes. 16 Q. Are you familiar with the 17 phrase "rechallenge protocol," Doctor? 18 A. Yes. 19 Q. Can you tell me what a 20 rechallenge protocol is? 21 A. Well, it's a generic -- a 22 rechallenge protocol is kind of a generic term in 23 which one would attempt to rechallenge a patient 24 that had had some event that may or may not have Page 184 1 been related to the drug to see if in fact that 2 event was related to the drug. 3 Q. So generally speaking, if a 4 person was on a drug and suffered an event, they 5 would be taken off the drug for a period of time 6 and then put back on the drug to see if the event 7 recurred while they were on the drug again? 8 A. That would be the usual way of 9 doing it. 10 Q. Are you aware that the FDA 11 requested that Lilly conduct a rechallenge study 12 on the issue of Fluoxetine and suicidality? 13 A. Well, I think you may have 14 over simplified some of the discussions about a 15 rechallenge protocol with the FDA. I know that a 16 rechallenge protocol was discussed with the FDA 17 as one potential approach to further examining 18 the Teicher phenomena. 19 Q. What other approaches were 20 suggested -- or discussed, I'm sorry? 21 A. Again, I can't construct all 22 the details, but we considered prospective 23 clinical trials, we considered a rechallenge 24 study, and we considered kind of an epidemiologic Page 185 1 study, a more or less structured epidemiologic 2 study. Those were generally the things I 3 remember considering. 4 Q. In fact Lilly actually 5 developed a rechallenge protocol and submitted it 6 to the FDA for approval, did it not? 7 A. I don't remember that 8 happening, but that's possible. 9 (PLAINTIFFS' EXHIBIT NO. 8 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 A. Were you expecting me to read 13 the whole thing? 14 Q. No, you don't have to do that. 15 MR. SMITH: And memorize it. 16 A. And memorize it, no problem, 17 just give me a week or so. 18 MR. MYERS: I think he's still looking 19 through it. 20 MS. ZETTLER: That's fine. 21 MR. MYERS: Okay. He's looked through 22 it. 23 Q. Have you had a chance to 24 review Exhibit 8? Page 186 1 A. Really, only superficially 2 because of the length. 3 Q. Do you recognize this 4 document? 5 A. I don't recognize the 6 document, per se. 7 Q. First page of the document is 8 a letter dated March 29, 1991 to the Food and 9 Drug Administration by you, correct? 10 A. Well, the letter is actually 11 written by Max Talbott, I co-signed it in Max's 12 absence. 13 Q. So he wrote the letter, but 14 for some reason left before he was able to sign 15 it? 16 A. That -- left, I don't know 17 what you mean by left. He wasn't there evidently 18 when this needed to go in, so I co-signed for 19 Max. 20 Q. Did you know what you were 21 co-signing? 22 A. Certainly, I mean it's evident 23 here. 24 Q. Did you understand it when you Page 187 1 signed it, even though you don't remember what it 2 is? 3 A. Oh, I assume I did understand 4 it, that would be my usual approach. 5 Q. It says we are submitting a 6 draft protocol entitled 7 Fluoxetine/Desipramine/Placebo Rechallenge Study 8 In Patients Who Developed Suicidal Ideation While 9 Under Treatment. Do you see that? 10 A. Yes. 11 Q. So is it fair to say that the 12 rechallenge protocol is attached to this letter, 13 Doctor? 14 A. The rechallenge protocol is 15 attached to this letter, that's right. 16 Q. Do you know if this study was 17 ever conducted? 18 A. Unless it has happened since I 19 left Lilly, it was never conducted. 20 Q. Why not, while you were there? 21 A. Well, first off, I think it's 22 fair to say that this was never submitted to the 23 FDA for, quote, approval, this was submitted for 24 information and comment. And I think that's what Page 188 1 this letter says. We mentioned that we're 2 specifically trying to refine the protocol, and 3 we're bringing in outside consultants to look at 4 the protocol. So it's fair to say that the 5 protocol, at this stage, when submitted, was not 6 in its final form, and it was still under 7 discussion. 8 Q. Was it ever submitted for 9 approval to the FDA while you were there at 10 Lilly? 11 A. That, I don't know, but I 12 don't believe it ever was. 13 Q. Why not? 14 A. Because it was viewed to be -- 15 to have limitations that made it almost 16 impossible to actually carry out. 17 Q. Like what? 18 A. Well, the problem with the 19 rechallenge protocol, though there are strengths 20 compared to the other approaches, still had a 21 number of critical limitations. One of those was 22 that we did not have a way to accurately assess 23 what Doctor Teicher was referring to, which was 24 the purpose of this rechallenge study. We had no Page 189 1 scales that were able to measure what Doctor 2 Teicher was attempting to measure. Secondly, the 3 second problem was there was a significant 4 ethical issue that came up in the trial because 5 you were taking patients that were, quote -- 6 that, quote, had severe suicidal ideation, and 7 submitting them again to the drug. And the only 8 way that one could ethically do that would be to 9 put them in the hospital, and if you did that, 10 then it wouldn't necessarily be a scientifically 11 valid rechallenge because the environment was 12 different. So for those two reasons, the view 13 was that such a study could not reasonably be 14 executed. I don't believe it was ever submitted 15 for approval. 16 Q. The FDA requested that Lilly 17 conduct a rechallenge study, did it not? 18 A. I don't know that the FDA 19 specifically ever requested it. 20 Q. When was the first time that 21 the issue of rechallenge on Fluoxetine came up 22 with regards to suicidality? 23 A. It's impossible for me really 24 to say when the first time the issue came up. Page 190 1 It's a very logical proposal to make on the 2 surface, it's very common in drug development to 3 suggest these kinds of approaches, so it probably 4 came up very early in concept. 5 Q. Why were you having difficulty 6 developing a scale or developing some way to rate 7 whether or not you were seeing Teicher's 8 described phenomena? 9 A. Well, to put it bluntly, I'm 10 not sure anybody knew what Doctor Teicher was 11 talking about. 12 Q. Did you ever ask Doctor 13 Teicher? 14 A. I never personally asked 15 Doctor Teicher. 16 Q. Did anybody from Lilly ever 17 ask Doctor Teicher? 18 A. There were -- I think you -- 19 well, there were visits to Doctor Teicher by -- 20 Q. Go ahead, I'm sorry. 21 A. I'm sorry, go ahead. 22 Q. You were about to say 23 something. 24 A. I don't know what it was. Page 191 1 Q. Isn't it true that Lilly is 2 the one who cut off communication with Doctor 3 Teicher with regards to this issue? 4 A. I don't know that that's 5 correct. That isn't the way I recall things. 6 (PLAINTIFFS' EXHIBIT NO. 9 WAS 7 MARKED FOR IDENTIFICATION AND 8 RECEIVED IN EVIDENCE.) 9 MR. SMITH: Is that stamp on there 10 bothering you, Doctor? 11 THE WITNESS: I'm okay now, I think, I 12 can read through it, it will just take me a 13 little longer. 14 MR. SMITH: Is that what was bothering 15 you initially, that stamp on there? 16 THE WITNESS: The stamp across, and 17 the small type on this particular document. 18 MR. SMITH: It makes it difficult to 19 read, doesn't it. 20 THE WITNESS: Yes. 21 MR. SMITH: We call that the Huff 22 stamp back in my office. 23 (DISCUSSION OFF THE RECORD.) 24 Q. Do you recognize this exhibit, Page 192 1 Doctor? 2 A. I don't recognize this 3 specific exhibit. 4 Q. Do you recall the telephone 5 conversation that you had with Doctor Leber on 6 December 19, 1990? 7 A. Well, I had a number of 8 conversations, but I don't remember this specific 9 one other than this recollection. This is 10 compatible with what I would have probably said. 11 Q. This is a memo to the file or 12 a note to the file written by you regarding a 13 telephone discussion that you had with Doctor 14 Paul Leber on December 19, 1990, correct? 15 A. Right. 16 Q. You called Doctor Leber, 17 correct? 18 A. Yes. 19 Q. Okay. The three issues that 20 you discussed was the current state of 21 discussions with the National Institute of Mental 22 Health about co-development of the scale for 23 evaluation of suicidality. Do you see that? 24 A. Yes. Page 193 1 Q. Do you recall trying to 2 contact or trying to discuss with the National 3 Institute of Mental Health co-development of a 4 scale for the evaluation of suicidality? 5 A. I was not myself the one that 6 made those contacts with the National Institute 7 of Mental Health. I'm speaking on behalf of the 8 group, I think, with this memo. 9 Q. Do you recall the group having 10 made contacts with the National Institute of 11 Mental Health on the co-development of the scale 12 for evaluation of suicidality? 13 A. Yes, there were contacts with 14 the National Institute of Mental Health. 15 Q. Did this have anything to do 16 with Doctor Miller's scale? 17 A. I really don't know that that 18 was directly linked to it. That's not the way I 19 remember it. 20 Q. What do you recall about 21 discussions between Lilly and the National 22 Institute of Mental Health regarding 23 co-development of a scale for the evaluation of 24 suicidality? Page 194 1 A. I can only really remember 2 very general facts, observations, that is that we 3 felt that the National Institute of Mental Health 4 would be an excellent body to help us develop a 5 valid scale, and that officials at the National 6 Institute of Mental Health, and I don't remember 7 names specifically, were contacted about 8 developing a scale or co-sponsoring a concensus 9 conference to try to get the best knowledge about 10 this whole issue of suicidality that had come up. 11 Q. To your knowledge was there 12 ever a co-development of a scale for evaluation 13 of suicidality conducted between Lilly and the 14 National Institute of Mental Health? 15 A. No. 16 Q. Why not? 17 A. Well, we continued to work 18 with them to possibly set something up, but there 19 was never enough interest on their part to really 20 develop a concensus conference or to focus effort 21 on this specific topic. 22 Q. Did the issue of whether or 23 not existing scales were available with the issue 24 of suicidality come up in discussions between Page 195 1 Lilly and the National Institute of Mental 2 Health? 3 A. Again, I don't recall being 4 involved directly in those discussions about the 5 existing scales, so I really couldn't answer the 6 question. 7 Q. Are you aware that in December 8 of 1990 there were other scales that had already 9 been developed and were already being used and 10 had already been validated that were meant to 11 evaluate suicidality in depressed patients? 12 Q. Well, there were other scales, 13 and they had been validated, but the initial 14 precipitating event in all of this was Doctor 15 Teicher's paper. What Doctor Teicher was 16 describing was something that he characterized as 17 a very different and intense suicidal behavior, 18 and there really were, to my knowledge, no scales 19 that addressed that specific point. 20 Q. Did you really need to just 21 look at suicidality as it was described by Doctor 22 Teicher, couldn't you have looked at suicidality 23 across the board related, regardless of how 24 severe and violent it was? Page 196 1 A. Again, suicidality was 2 assessed as part of the clinical trials in the 3 Hamilton depression scale, and that was a general 4 evaluation of suicidality. And the question, 5 again, that precipitated it was Doctor Teicher's 6 specific description of intense suicidal ideation 7 for which there was no scale to assess that 8 situation. 9 Q. Doctor, isn't it true that the 10 Hamilton depression scale, item three, which 11 relates to suicidality is not meant in and of 12 itself to rate suicidality in a patient? If you 13 were going to conduct -- 14 MR. MYERS: Let him finish -- are you 15 withdrawing your question? 16 MS. ZETTLER: Yes, let me withdraw it. 17 Q. If you're going to conduct a 18 study to -- 19 MR. MYERS: New question. 20 Q. -- investigate suicidality in 21 a group of depressed patients, whether or not 22 it's on Fluoxetine or just to look at an 23 incidence of suicidality, would you use the 24 Hamilton depression three question or the one Page 197 1 item on the Hamilton depression scale as your 2 sole rating scale or judge of whether or not 3 people are becoming depressed or are suffering 4 from depression? 5 A. Well, I mean the Hamilton 6 depression scale is commonly used to assess 7 depression, that was your question, you would 8 commonly use the Hamilton depression scale. 9 Q. It's not commonly used in and 10 of itself to assess suicidality, is it? 11 A. That wasn't your question. 12 Q. Okay. 13 A. Maybe you want to rephrase 14 your question. 15 Q. Is the Hamilton depression 16 rating scale used in and of itself to assess 17 suicidality? 18 A. Well, it is a tool that can be 19 used, yes. If you wanted to intensely study 20 suicidality, it probably would not be the optimal 21 tool. 22 Q. Okay. So if you're going to 23 construct a clinical trial to evaluate 24 suicidality and the use of Fluoxetine, or any Page 198 1 other treatment, would you use the Hamilton 2 depression rating scale by itself, without any 3 additional rating scales or any additional 4 testing, to try to evaluate whether or not people 5 are becoming suicidal or what the incidence of 6 suicidality is? 7 A. If you were going to set up a 8 prospective study, it probably wouldn't be the 9 optimal choice. It doesn't mean that it's 10 invalid, it just means that it's not the optimal 11 choice. 12 Q. To your knowledge has the 13 Ham-D scale been validated for rating 14 suicidality? 15 A. I don't know what validation 16 has taken place with regards to that subitem. 17 Obviously the Hamilton depression scales had a 18 lot of use in assessing depression. 19 Q. There are better scales out 20 there than the Ham-D-3 question to rate 21 suicidality, are there not? 22 A. Yes, I think there probably 23 are, yes. 24 Q. Have you ever heard of the Page 199 1 adult suicidal ideation questionnaire? 2 A. I think that probably came up 3 in our discussion. 4 Q. To your knowledge is that a 5 valid suicidality questionnaire, suicidality 6 ideation questionnaire? 7 A. I don't know what information 8 has been used to validate it. 9 Q. Couldn't a study -- couldn't a 10 study have been run, Doctor, to research or 11 investigate whether or not Fluoxetine causes or 12 intensifies suicidality in depressed patients, 13 regardless of how severe the suicidality is or 14 how intense it is? 15 A. Well, again, the question at 16 hand was whether Doctor Teicher's observation -- 17 Q. That's not my question, please 18 listen to my question. Couldn't Lilly have run a 19 study to investigate whether or not Fluoxetine 20 causes suicidal ideation or intensifies suicidal 21 ideation in depressed patients taking the drug? 22 A. Well, I think one of your 23 previous exhibits points out the limitations in 24 any such study, whether it's an epidemiologic Page 200 1 study or a prospective study or rechallenge 2 study. 3 Q. I'm not asking -- 4 MR. DOWNEY: Move to strike as 5 nonresponsive. 6 Q. Could it have been conducted 7 or not have been conducted? 8 A. Could what have been 9 conducted? 10 Q. Is it possible for Lilly to 11 conduct a study to investigate whether or not 12 people who take their drug Fluoxetine become 13 suicidal or whether their suicidal ideation 14 increases because of the drug? 15 A. Any study conducted in the way 16 you described it would have severe limitations in 17 terms of scientific interpretation, and the 18 reasons have been outlined in the memo to the 19 FDA. 20 MR. DOWNEY: Move to strike as 21 nonresponsive. 22 Q. Regardless of whether or not 23 there are limitations, Doctor, could the study 24 have been conducted? Page 201 1 A. Any study could be conducted. 2 Whether it means anything or not is another 3 matter. 4 Q. Let's get back to the 5 rechallenge study. Your testimony was that one 6 of the main reasons that the rechallenge study 7 was not submitted to the FDA for approval was 8 because it was difficult to develop a scale or 9 develop a means of rating what Doctor Teicher saw 10 in or reported in his article, the intense 11 suicidal ideation that he reported in his 12 article, correct? 13 A. Again, you've added so many 14 things, can you make it a nice clear, simple 15 question? 16 Q. Tell me again, what -- the 17 Teicher related reason why the rechallenge 18 protocol was not submitted to the FDA for 19 approval was what? 20 A. Well, the reason the 21 rechallenge protocol was not submitted for 22 approval is that it was not ready to be submitted 23 for approval. It was submitted for information, 24 for comment, and to notify the FDA that we were Page 202 1 working with other people in addition to the FDA 2 to identify a proper study to address this 3 question. 4 Q. Would it surprise you if I 5 told you that Doctor Talbott testified that the 6 reason that the rechallenge protocol -- the study 7 was never conducted was because the September, 8 1991 advisory committee meeting was thought to 9 have put the issue of suicidality as it related 10 to Fluoxetine to rest and there was no need to 11 conduct a study? 12 A. Well, that may have been 13 Doctor Talbott's impression at the time, I don't 14 know. It wouldn't surprise me what was said, but 15 if that's the question, does it surprise me, no, 16 that doesn't surprise me. 17 Q. What was the problem with 18 involving Doctor Teicher with being able to put 19 together the protocol? 20 A. Well, the problem was that 21 because of his involvement in -- I'm sorry, could 22 you repeat the question? 23 Q. Earlier you testified that 24 part of the reason that the protocol was not -- Page 203 1 had not, at least while you had been there, been 2 submitted to the FDA for approval is because 3 you're having difficulties with rating scales or 4 the ability to figure out a way to determine 5 whether or not patients were becoming suicidal in 6 the way that Doctor Teicher described, correct? 7 A. Yes. 8 Q. Okay. And my question was 9 whether or not you recall asking Doctor Teicher 10 to participate in developing a scale or in some 11 way figuring out how to structure the study so 12 that you could look at that phenomena, correct, 13 do you recall that question? 14 A. You asked -- you asked a 15 series of questions along those lines, yes. 16 Q. Do you recall having 17 difficulties contacting Doctor Teicher? 18 A. Yes, there were. And my 19 recollection, again, was that there were two 20 meetings that attempted to contact Doctor 21 Teicher, the first was successful, they were able 22 to talk to Doctor Teicher, but my recollection 23 was in the second one they were unable to talk to 24 Doctor Teicher. Page 204 1 Q. Why? 2 A. It was -- again, my 3 recollection was that it was Doctor Teicher that 4 was not willing to meet at that time. That's my 5 recollection. 6 Q. And who tried to meet with 7 Doctor Teicher when he was not willing to meet? 8 A. Well, I'm not sure, I can't 9 remember exactly who went down. There were two 10 people from Lilly, I think Doctor Masica and 11 Doctor Beasley -- I'm not sure whether it was 12 Doctor Beasley or exactly who it was, but I think 13 it was Doctor Masica and Doctor Beasley. 14 Q. Why didn't you just talk to 15 Jonathan Cole? 16 A. I think they did talk to 17 Jonathan Cole. 18 Q. Jonathan Cole was a co-author 19 on the Teicher article, wasn't he? 20 A. Jonathan Cole was a co-author, 21 yes. 22 Q. Jonathan Cole also acted as a 23 clinical investigator on Lilly Fluoxetine trials, 24 hadn't he? Page 205 1 A. I think Doctor Cole was 2 involved in some trials as well. 3 Q. So Lilly was pretty confident 4 that he was a competent psychiatrist, were they 5 not? 6 A. I think that Doctor Cole was 7 viewed as a reasonable psychiatrist. 8 Q. So why didn't you just develop 9 a scale with Doctor Cole if Doctor Teicher 10 wouldn't cooperate with you? 11 A. I think there was a real 12 question whether Doctor Cole really understood 13 what Doctor Teicher was describing. 14 Q. So you have a competent 15 psychiatrist that Lilly trusted enough to allow 16 to conduct clinical trials on its drug 17 Fluoxetine, but they weren't confident enough 18 that Doctor Cole really understood the article 19 that he co-authored with Doctor Teicher, is that 20 what you're saying? 21 A. That is what I'm saying. 22 Q. Why, what was it about Doctor 23 Cole that made it -- made you guys nonconfident 24 or not confident that he was competent to discuss Page 206 1 what Doctor Teicher was seeing? 2 A. Again, I did not meet with 3 Doctor Cole, but Doctor Cole contributed only one 4 of the patients to Doctor Teicher, and I think 5 the feeling was that Doctor Cole couldn't really 6 adequately represent all that Doctor Teicher was 7 describing. 8 Q. Wasn't Doctor Cole's patient 9 one of the clinical trial patients, the one he 10 contributed to the study, to the paper? 11 A. I don't recall that that was 12 the case. 13 Q. How about Carol Glod, did you 14 talk to Carol Glod? 15 A. No, not that I am aware of. 16 The name isn't even familiar to me. 17 Q. Is it your belief that Doctor 18 Cole really didn't know what Doctor Teicher was 19 saying even though he co-authored the article 20 with him on intensification of suicidal ideation? 21 A. The way I would put it is I 22 don't think that we felt that -- again, maybe I 23 should say, I didn't feel, based on the 24 information, maybe others felt differently, I Page 207 1 don't know, but there were concerns that Doctor 2 Cole could not represent the spectrum of 3 observations that Doctor Teicher did because 4 Doctor Cole really only contributed one of the 5 patients. 6 Q. Do you know if Doctor Cole 7 read the manuscript for Doctor Teicher's article 8 before it was submitted for publication? 9 A. I don't know that he did. 10 Q. Do you know if he ever 11 discussed the article with Doctor Teicher before 12 it was submitted for publication? 13 A. Again, I don't know that he 14 did, I just don't know. 15 Q. Is it your belief that Doctor 16 Cole agreed to co-author an article on a subject 17 that he didn't fully understand? 18 A. You're asking me to speculate. 19 I don't know Doctor Cole or the situation well 20 enough to make a judgment. 21 Q. I guess I'm a little confused 22 as to what you say. You say based on the 23 information you had, you weren't confident that 24 he fully understood the spectrum of what Doctor Page 208 1 Teicher was seeing, right? 2 A. Right. 3 Q. What information? 4 A. Again, let me try to explain. 5 Doctor Cole provided only one of the patients, so 6 he could really effectively only describe the one 7 that he saw. And the view was that if we were 8 ever to have a valid scale, we would need to be 9 sure that we represented the whole spectrum of 10 what Doctor Teicher observed, and the feeling was 11 that Doctor Teicher would be the best, maybe the 12 only person, that could effectively do that. 13 Q. Did you ever ask Doctor Cole 14 if he discussed with Doctor Teicher the spectrum 15 of what he saw in the rest of the patients in the 16 study? 17 A. I never personally talked to 18 Doctor Cole about that. 19 Q. Do you know if anybody at 20 Lilly did? 21 A. Again, there were people that 22 met with Doctor Cole, but I don't know whether 23 they asked about that specifically. 24 Q. Go back to Exhibit 9, under Page 209 1 number two that was discussed in the phone call 2 between you and Doctor Leber. 3 A. Right. 4 Q. It says current state of our 5 contacts with blank, and I'm assuming that's 6 Teicher, correct? 7 A. That's my assumption too. 8 Q. Assuming that it's Teicher, it 9 says I explained that we have stopped attempts to 10 meet with blank because of his current and 11 planned participation in litigation, correct? 12 A. That's what it says, yes. 13 Q. Do you recall trying to 14 contact Doctor Teicher because you learned that 15 he may or may not be involved with litigation on 16 Fluoxetine? 17 A. I recall in general, yes, 18 that. 19 Q. Did Doctor Teicher ever refuse 20 to discuss Fluoxetine with Lilly employees 21 because of his alleged planned participation in 22 litigation? 23 A. Again, other than the one 24 situation in which my recollection was that he Page 210 1 didn't -- couldn't meet, wouldn't meet with Lilly 2 folks, I don't know of any other situations in 3 which there was a request to meet with him, in 4 which he refused to meet because of litigation. 5 Q. Okay. At that point, was it 6 pretty clear that Doctor Teicher and you weren't 7 going to be able to develop a scale with Doctor 8 Teicher regarding his intensification of 9 suicidality that he saw? 10 A. Again, unless there was 11 something that changed with regard to Doctor 12 Teicher and his legal involvement, it was going 13 to be very difficult to meet with him. 14 Q. If you go back to Exhibit 8. 15 MR. MYERS: The protocol? 16 MS. ZETTLER: Yes. 17 Q. Go back to Exhibit 8. This 18 letter that was authored by you submitting the 19 draft of the protocol to the Food and Drug 20 Administration is dated March 29, 1991, correct? 21 A. Right. 22 Q. And that's about four months 23 after your discussion with Doctor Leber where you 24 informed him that you weren't going to be Page 211 1 contacting Doctor Teicher anymore, correct? 2 A. That's right. 3 Q. Anywhere in here, and you can 4 take your time in looking at it, but is there 5 anywhere in the protocol that's attached to 6 Exhibit No. 8 do you say that you're not going to 7 be able to conduct this study because you can't 8 put together a sufficient rating scale? 9 A. Well, do you want me to take 10 the time to read the whole thing? You're saying 11 anywhere in there, I don't know. If you want me 12 to read the whole thing, then I'll sit and read 13 it, but I don't know that you're going to get 14 much done the rest of the afternoon. 15 Q. Let's go to page seven, we'll 16 do it your way. 17 A. Page seven of the protocol? 18 Q. Yes. Under section G, 19 Efficacy And Safety Data, okay, do you see that? 20 A. Under part G? 21 Q. I think we have two different 22 pages going, Doctor. Four six six nine four in 23 the upper right-hand corner. 24 A. Four six six nine four, yes. Page 212 1 Efficacy and Safety Data, yes, okay. 2 Q. It says toward the middle of 3 the page under Study Period I, all eligible 4 patients will receive the following baseline 5 evaluations at visit one. Do you see that? 6 A. I don't, maybe you can point 7 to it. Yes, all eligible patients will receive 8 the following baseline evaluations at visit one. 9 Q. A, HAMD-28. 10 A. Yes. 11 Q. B, Y hyphen BOC. 12 A. Right. 13 Q. C, scale for suicidal 14 ideation? 15 A. Yes. 16 Q. What scale for suicidal 17 ideation? 18 A. Well, again, this was a draft 19 protocol. And the way I interpret that, that is 20 the yet to be developed scale based on working 21 with outside individuals to come up with a valid 22 assessment. So again, this is a draft protocol, 23 and for exactly that reason, it couldn't be 24 implemented because the scale didn't exist. Page 213 1 That's the way I would read that, I don't know 2 what other scale that would be. 3 Q. Was Doctor Miller trying to 4 develop a scale for suicidal ideation based on 5 Doctor Teicher's observations or was he 6 developing a scale based on a scale he had 7 already developed? 8 MR. MYERS: At what point, at the same 9 time as this letter? 10 MS. ZETTLER: At any point in time. 11 A. My recollection of Doctor 12 Miller's efforts were to attempt to develop a 13 scale that more specifically addressed some of 14 the specific aspects as described by Doctor 15 Teicher. 16 Q. And to your knowledge was a 17 scale ever developed by Doctor Miller? 18 A. I don't recall ever seeing the 19 scale, although there was -- well, I don't recall 20 ever seeing the scale. 21 Q. Okay. Would it surprise you 22 if I told you that Catherine Mesner testified 23 that Doctor Miller had developed a scale and in 24 fact had just, within the past couple of years, Page 214 1 completed a clinical trial to validate the scale? 2 A. No, that wouldn't surprise me 3 at all, that wouldn't surprise me. 4 Q. Turn to probably the fourth 5 page from the end of this exhibit. 6 A. Can you give me a page number? 7 Q. Upper right-hand corner, four 8 six seven zero six. 9 A. Four six seven zero six, yes. 10 Q. The page is entitled Appendix 11 D, correct? 12 A. Right. 13 Q. And it's called Scale For 14 Suicide Ideation, paren, for Ideators, close 15 paren, correct? 16 A. Right. 17 Q. And it goes and lists a bunch 18 of different questions, does it not? 19 A. Yes. 20 Q. And these questions are really 21 being asked of the patients themselves, correct? 22 A. I wouldn't call them 23 questions, but yes. 24 Q. Okay. And it asks a bunch of Page 215 1 different characteristics of attitude, like, for 2 instance, characteristics of attitude toward 3 living slash dying, correct? 4 A. Yes. 5 Q. And it says wish to live, 6 right? 7 A. Yes. 8 Q. Wish to die, correct? 9 A. Yes. 10 Q. Reason for living slash dying, 11 correct? 12 A. Yes. 13 Q. Okay. And it goes on to list 14 characteristics of the suicide ideation slash 15 wish at the bottom of the page, correct? 16 A. Yes. 17 Q. And it goes on for another two 18 and a half pages with questions or 19 characteristics, correct? 20 A. Yes. 21 Q. Okay. Where did this scale 22 come from? 23 A. I don't know except what 24 information is provided here, it says Page 216 1 acknowledgment to author at the bottom. 2 Q. Does it say who the author is? 3 A. The acknowledgment to author 4 on page four six seven oh nine, it says Aaron T. 5 Back, M.D. 6 Q. Aaron T. Beck, M.D.? 7 A. I'm sorry, Beck, yes, or Back, 8 I can't tell from the print. 9 Q. That's because the 10 confidential stamp is over the word, right? 11 A. Right. 12 Q. Do you know Aaron T. Beck or 13 Back? 14 A. No. 15 Q. Do you know if this person was 16 ever retained by Lilly to develop a scale? 17 A. I don't know. Again, if this 18 was a copyrighted scale, I imagine there was some 19 payment involved to use this scale or even submit 20 this scale to the FDA, but I don't know that. 21 Q. And the scale was copyrighted, 22 at least according to this, in 1979, was it not? 23 A. Yes. 24 Q. Other than the fact that you Page 217 1 wanted to look for the phenomena that was 2 described in Doctor Teicher's article, is there 3 any reason why the protocol, as it stands in this 4 draft, could not have been conducted? 5 A. Well, I think I cited already 6 one other reason, and that was the concerns about 7 ethics involved in the trial. And in order to 8 complete the trial ethically, there were concerns 9 about the scientific validity of the trial. So 10 that was also a hurdle that was considered at 11 this time. 12 Q. Because you felt you would 13 have to hospitalize patients for their own safety 14 in the study, correct? 15 A. Because you would have to 16 hospitalize patients, but when you hospitalized 17 them, then they were no longer in the setting in 18 which the phenomena occurred in the first place. 19 So including that, it either did or didn't 20 produce the same event on rechallenge, would be 21 open to criticism. 22 Q. Well, then, aren't you 23 describing the same type of phenomena that occurs 24 with your efficacy clinical trials because you Page 218 1 have such strict control over the types of 2 patients they're monitoring and things like that? 3 A. No. 4 Q. Why is that different? 5 A. Because the primary comparator 6 groups are two groups that are treated 7 essentially identically. In this setting, you've 8 got a comparison of the patient to themselves, 9 they had the event and then you are rechallenging 10 them to see if you can reproduce that same event, 11 and therefore, the two settings before and after 12 are not the same, you can't compare those things. 13 Q. Doctor, isn't this a 14 double-blind controlled study where different 15 patients on different treatments would be 16 randomized to -- a person who is on amitriptyline 17 could be randomized to Fluoxetine, right? 18 A. Yes. But that's not the 19 primary question in the study. The comparator 20 arm was put in there because there probably would 21 be some patients who would have, on rechallenge, 22 expressed those events, but you can't -- unless 23 you control that, and you don't let the patient 24 know what they're on, you can't reach a valid Page 219 1 conclusion. If somebody had said I had severe 2 suicidal ideation when I was treated with Prozac, 3 and then you brought them in the hospital and 4 treated them with Prozac, it's very likely they 5 could say I'm having severe suicidal ideation, 6 and there's no independent way to confirm that. 7 Only if you randomize those to Prozac or some 8 other therapy, and then tested them when the 9 patient did not know what they were receiving, 10 could you test that validly. And the question 11 about before and after, whether it occurred, is 12 still the key question for the patient, and 13 you've got to control both of those settings, 14 they need to be ideal before you could answer the 15 question about whether it happens on rechallenge 16 at all. 17 Q. Isn't that the same reason you 18 use double-blind efficacy studies, because 19 patients can assume that they have gotten better 20 on a drug that they've already taken before? 21 A. Right, but you're comparing in 22 that situation two different groups in terms of 23 the improvement in the suicidal ideation. In 24 this situation, you're trying to replicate a Page 220 1 specific event that occurred in that patient. So 2 it's really not valid -- it's very questionable 3 scientifically to be able to conclude that it did 4 or didn't occur on rechallenge if you don't have 5 the setting the same before and after the 6 rechallenge, if you understand what I'm saying. 7 Q. What I don't understand is if 8 this was such a difficult study to conduct, and 9 it was so questionable scientifically, why did 10 the Food and Drug Administration ask Lilly to 11 conduct such a study? 12 A. Again, I don't know what 13 document you're specifically referring to when 14 you say they requested that we conduct such a 15 study. 16 (PLAINTIFFS' EXHIBIT NO. 10 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 A. I'm sorry, again I'm having 20 trouble, some of the print is hard to read. I 21 think I've reviewed it. 22 Q. Did you attend the meeting at 23 the FDA regarding the rechallenge protocol on May 24 13, 1991? Page 221 1 A. I believe I did attend that 2 meeting. 3 Q. Did the FDA at that meeting 4 request that Lilly proceed with the rechallenge 5 study? 6 A. Again, I think your 7 characterization of this memo is not at all the 8 way that I read it. 9 Q. How do you read it, Doctor, 10 why don't you tell me? 11 A. The FDA is agreeing that we 12 should continue to try to develop the rechallenge 13 protocol, and the concept related to it, but a 14 number of times in this memo they cite the 15 specific reservations that I have enumerated to 16 you regarding the limitations of the rechallenge 17 protocol. 18 Q. Where? 19 A. On the second page Doctor 20 Leber also had a concern about the rechallenge 21 study in that patients who had previously been 22 exposed to the drug and had suicidal symptoms may 23 be biased on redevelopment of such symptoms and 24 treatment. The other one that I would cite is on Page 222 1 the first page, under item one, the third bullet 2 point. This would allow the FDA and Lilly to 3 determine if the study was feasible or not. That 4 doesn't imply that they told us to do the trial. 5 And will give a feel for the data that we're 6 collecting. I mean both of those points indicate 7 that they were not directing us in this memo to 8 carry out that trial. 9 Q. Let's go back to your first 10 point, that you first pointed out about Doctor 11 Leber, okay, where you quoted Doctor Leber also 12 had a concern about the rechallenge study in that 13 patients who had previously been exposed to the 14 drug and had suicidal symptoms may be biased on 15 redevelopment of such symptoms and treatment, 16 correct, is that what you quoted? 17 A. Yes. 18 Q. You forget to mention that it 19 goes on to say which is why he made the 20 suggestion to look at the incidence in garden 21 variety depression patients treated with these 22 agents for the first time, correct? 23 A. That's what it said. I didn't 24 neglect to read it, it just didn't seem like that Page 223 1 was the relevant point, but that's fine. 2 Q. Did Lilly ever do that, look 3 at the incidence in garden variety depression 4 patients treated with the agents for the first 5 time? 6 A. Again, that was really the 7 essence of the analysis of the studies that were 8 done, that the reanalysis of the double-blind 9 data base. 10 Q. Those reanalyses had already 11 been given to Leber and the FDA long before this 12 meeting, at least almost a year before this 13 meeting, were they not? In fact this was about 14 the time when Doctor Beasley's article was 15 actually published. 16 A. No, I don't believe that's 17 true. 18 Q. When was his article 19 published? 20 A. I think his article was 21 published about six months after this memo. 22 Q. It was provided to the FDA, 23 the results of the analysis was provided to the 24 FDA long before this meeting though, were they Page 224 1 not? 2 A. I don't know exactly when 3 those data were provide to the FDA, but you 4 suggested that Doctor Beasley's paper was 5 published, and I don't believe that's true. 6 Q. I think I was thinking about 7 when it had been submitted to the New England 8 Journal of Medicine and had been rejected, so 9 you're probably right. But let's talk about 10 whether or not -- 11 MR. MYERS: Nancy, don't smart off to 12 the witness, that's cheap. 13 MR. DOWNEY: Let's take a break. 14 (A SHORT RECESS WAS TAKEN.) 15 * * * * * * * * * * 16 EXAMINATION 17 BY MR. SMITH: 18 Q. Doctor Zerbe, my name is Paul 19 Smith, and I'm from Dallas, Texas, and I 20 represent a number of individuals whose families 21 and lives have been affected by virtue of adverse 22 experiences that their loved ones have had, that 23 we claim they've had, as a result of adverse 24 experiences with Prozac, all right? Page 225 1 A. Yes. 2 Q. I'm their lawyer, and I filed 3 suit against Eli Lilly on their behalf. If I ask 4 you any questions that you don't understand, 5 would you let me know, sir? 6 A. I will. 7 Q. We had originally scheduled 8 your deposition for more than one day, however 9 Mister Richard Wood could only give his 10 deposition yesterday, and so we opted to take him 11 instead of you yesterday. 12 A. I don't understand, he's 13 retired and I'm working. 14 Q. My question to you is: Do you 15 have any problem at this time, Doctor Zerbe, in 16 making yourself available within the next thirty 17 to forty-five days for a continuation of this 18 deposition? We've just begun to scratch the 19 surface with you to be honest. 20 A. You know, it depends on my 21 schedule, but I'm here to cooperate as best I 22 can. You're understanding, too, the difficulty 23 that I have. 24 Q. We certainly intend to try to Page 226 1 schedule this at a time and a place convenient to 2 you. My question to you is is there something 3 pressing that's going to prevent you from giving 4 your deposition that you know of now within the 5 next thirty to forty-five days? 6 A. You mean are there specific 7 conflicts that I have in terms of specific days? 8 Q. Specific weeks, let's say. 9 A. I don't have my calendar with 10 me. I will be gone all of next week, I know -- 11 that's about as far ahead as I can think anymore. 12 Q. Well, we have Doctor Beasley 13 and Doctor Perelman next week, so -- 14 MR. MYERS: Paul, we'll work on that 15 collectively with you and Doctor Zerbe. 16 Q. But my point is, and I want to 17 be clear with you this afternoon, that you think 18 you will be able to make yourself available on 19 reasonable notice within the next thirty to 20 forty-five days? 21 A. I think if everybody can work 22 with the calendar, we'll all do our best. 23 Q. I just want to make sure that 24 you weren't going off for some sabbatical in Page 227 1 Europe or something for some six month period of 2 time. 3 A. I don't plan to. 4 Q. I would like to back up a 5 little bit, Doctor Zerbe. As I understand it, 6 you received your M.D. degree, did you not? 7 A. Yes. 8 Q. When and where? 9 A. 1975 at Indiana University. 10 Q. Then after you received your 11 postgraduate training or did postgraduate work, 12 you did work in internal medicine and 13 endocrinology? 14 A. Yes. 15 Q. And thereafter became Board 16 certified in internal medicine? 17 A. Yes. 18 Q. Were you ever in private 19 clinical practice? 20 A. No. 21 Q. Did you ever practice at a 22 hospital on a regular basis seeing patients in a 23 clinical setting? 24 A. That's certainly part of Page 228 1 training. Fairly intensively we saw patients in 2 the hospital as part of our training, but I was 3 never in private practice. 4 Q. I was under the impression, 5 and maybe I was wrong, that in order to receive 6 Board certification in any particular specialty, 7 that you had to have a certain amount of clinical 8 practice in order to be even eligible to take the 9 Board exams? 10 A. You have to have some clinical 11 practice, and that's what my postgraduate 12 training was. Internship and residency, and 13 clinical work, as part of my fellowship at 14 Indiana, were all clinical, they were all 15 clinical activities that allowed me to be Board 16 eligible in internal medicine. 17 Q. And when did you receive your 18 Internal Medicine Board certification? 19 A. Again, I think I answered that 20 earlier. I'm not sure of the exact date, but it 21 was approximately 1978 or '79. 22 Q. But you have not treated 23 patients on an ongoing basis in a private 24 situation? Page 229 1 A. I have never been in private 2 practice. 3 Q. You've never had any training 4 in psychiatry or psychology or a discipline such 5 as that? 6 A. Well, there is -- part of 7 medical training does include rotations in 8 psychiatry, and I of course had those as part of 9 my training. 10 Q. As an internist? 11 A. No, in medical school. 12 Q. But have you received any 13 training in psychiatry or psychology other than 14 that training in psychiatry and psychology that 15 say a general practitioner might have? 16 A. No, I don't believe so, no 17 specialty training in psychiatry. 18 Q. And no specialty practice 19 either? 20 A. That's correct. 21 Q. Are you of the opinion from a 22 medical standpoint that suicidality is part of 23 the illness of depression? 24 A. That's my opinion, yes. Page 230 1 Q. And when did you come to that 2 opinion? 3 A. I think very -- it's a pretty 4 elementary observation in psychiatry, and that 5 would be the type of information that would be 6 something conveyed even in medical school 7 training in psychiatry, that suicide and 8 depression are in some way linked. 9 Q. And at the time that you were 10 in medical school and formed that opinion, nobody 11 had even developed Prozac yet, had they? 12 A. I don't believe that Prozac 13 was -- had ever been -- certainly never been in 14 clinical studies at that point. 15 Q. No humans had ever consumed 16 Prozac back when you were in medical school? 17 A. I think that's correct, yes. 18 Q. When you formed the opinion 19 that suicidality and depression were linked, 20 correct? 21 A. Yes. 22 Q. Now, would it be correct that 23 you had the opinion that the link between 24 depression and suicidality was caused by the Page 231 1 person's underlying disease of depression, is 2 that correct, that you held that opinion? 3 A. I held the opinion that there 4 was an association between suicide and 5 depression. 6 Q. Early on? 7 A. Yes. 8 Q. So you had a preconceived 9 opinion and idea concerning the underlying 10 disease of depression and its relation to 11 suicidality before Prozac ever came on the scene, 12 didn't you? 13 A. I think that I held the 14 opinion that many others in that, yes. 15 Q. I'm not talking about anybody 16 else's opinion, I'm talking about your opinion, 17 okay? 18 A. Right. 19 Q. And would that be true, that 20 you held that opinion before Prozac ever came on 21 the scene? 22 A. Yes. 23 Q. Did you ever engage in an 24 investigation yourself or into an inquiry Page 232 1 yourself concerning whether or not Prozac could 2 be causally related to suicide in depressed 3 individuals? 4 A. Could you clarify what you 5 mean by engaged in an investigation myself? 6 Q. Did you make an inquiry 7 yourself, did you say I would like to see the 8 data myself or I would like to review this issue 9 or review the literature myself? 10 A. I was very aware of the data 11 at the time the question came up about 12 suicidality. So defined in that way, the answer 13 I would have to give it yes, I was involved in 14 looking at data and reaching conclusions about 15 those data on that question. 16 Q. When did the question first 17 come up in your mind? 18 A. Well, I think the first 19 question came up in the -- as we were talking 20 before, in the situation in Germany. 21 Q. That would have been 1984, 22 1985, right? 23 A. It's about that time, yes. 24 Q. By 1984 and 1985, there had Page 233 1 been a large number of people who had been 2 exposed to Prozac, had there not, in the clinical 3 trials? 4 A. As part of clinical trials, 5 there was already a reasonably large data base. 6 Q. And up until 1984 and 1985, do 7 I understand it that no one at Lilly had examined 8 that data base to address the question of whether 9 or not there was a relationship between Prozac 10 and suicide? 11 A. I couldn't say that that was 12 true. I was not involved in the analysis of the 13 Prozac data base at the time of the NDA filing in 14 1983, and certainly information was available at 15 that time with regard to the suicidal component 16 of the Hamilton Depression Scale, and there were 17 adverse events that were reports of suicides as 18 part of the clinical trials as one might expect 19 in depression. The extent of analysis at that 20 time, I don't know. 21 Q. But I understand there may 22 have been some data during the clinical trials 23 where suicide was reported or suicidal attempts 24 and suicidal ideation had been reported, correct? Page 234 1 A. Yes. 2 Q. But my question was, up until 3 1984 and 1985 when the German government 4 questioned whether or not there was a causal 5 connection between the suicide and Prozac, do you 6 know personally whether or not that issue had 7 ever been addressed by anybody at Lilly? 8 A. I don't know whether it had or 9 hadn't prior to that time. 10 Q. Who would know that? 11 A. I would say the one most 12 likely to know would be probably Doctor Paul 13 Stark. 14 Q. We've taken Doctor Stark's 15 deposition, and his testimony was that the issue 16 had never been addressed until the Teicher 17 article even, or as long as he was employed by 18 Eli Lilly and Company, he had never addressed the 19 issue of whether or not there was a causal 20 connection between Prozac and suicide. Will you 21 take my word for it? 22 A. Yes. 23 Q. So if he hadn't addressed it, 24 can you think of anybody else that might have Page 235 1 addressed it? 2 A. I really -- I can't, I can't 3 name individuals. 4 Q. But if in your judgment, if 5 anybody were to have been charged with the 6 responsibility of addressing that issue, it would 7 have been Doctor Stark, is that right? 8 A. I think so, yes. 9 Q. Because he was the medical 10 monitor of the clinical trials up to 1984 and 11 1985? 12 A. Until 1984, middle of 1984. 13 Q. All right. He was the medical 14 monitor at least at the time of the initial IND 15 submission? 16 A. I don't know about the initial 17 IND submission. 18 Q. Or the submission in '83. 19 A. The initial -- the only NDA 20 submission. 21 Q. All right. Would it be fair 22 to state, then, that when the issue in 1984 or 23 1985 was first raised as to you, you had a 24 preconceived notion that there was no causal Page 236 1 connection between Prozac and suicide? 2 A. I think the wording 3 preconceived may be a little bit -- suggests that 4 my views were a bit too concrete. It was -- 5 Q. Well, I'll define that for you 6 if that will help you. 7 MR. MYERS: Let him finish his answer 8 first, please. 9 MR. SMITH: I thought he was having 10 difficulty in answering my question, and I was 11 going to define that. 12 MR. MYERS: Why don't you finish, and 13 then let Mister Smith define. 14 A. I think there was no reason to 15 believe otherwise, but we were always open to 16 evaluating any hypothesis and looking at any data 17 that was presented to us with an open mind. 18 Q. All right. But even though 19 you say the preconceived notion might be too 20 strong, you certainly were of the scientific 21 opinion at the time it first arose that any 22 occurrences of suicide up until that time which 23 had presented during the clinical trials was 24 related to the fact that suicide and depression Page 237 1 were linked, wouldn't that be a fair statement? 2 A. I think that was our 3 assessment of the available data, yes. 4 Q. And that's what I believe 5 Doctor Stark had testified, was that anytime you 6 had seen suicide that had occurred during the 7 clinical trials, the assumption was automatic 8 that that was because you were conducting 9 clinical trials on depressed individuals and 10 depressed individuals were more likely to engage 11 in suicidal behavior than those that were 12 nondepressed. Would that be correct? 13 A. Again, I'm not sure that your 14 wording is exactly the way that I would describe 15 it. We were never automatic in assuming anything 16 about the data. I think we tried to be very 17 systematic in looking at all data to make sure 18 that we gave it a thorough evaluation and reached 19 a good sound scientific conclusion. 20 Q. But the fact is, even though 21 I'm sure that that may have been your intention, 22 the fact is is that the data had never been 23 analyzed up until this issue came up with the 24 German government to determine whether or not Page 238 1 there was a link between Prozac and suicide? 2 A. Well, again, I think it's 3 difficult to be so blanket in your statements 4 with regard to never been analyzed, it implies 5 that we had never looked at individual cases of 6 suicidality or suicide and so forth. And I think 7 all those cases were looked at, and we tried to 8 look at them with an open mind. No one had 9 reached any conclusion that there was any link at 10 that point. 11 Q. But nobody had looked at that 12 data to question whether or not there was a link 13 between Prozac and those suicides that you had 14 seen, had they? 15 A. There was no suspicion that 16 that was the case. 17 Q. That's my point, that up until 18 the time it was raised in '84 or '85 by the 19 German government, there wasn't any suspicion of 20 any link because there was the general opinion 21 held in the scientific community that if you saw 22 suicide in a clinical trial where you were 23 looking at depressed individuals, that it would 24 more likely be a result of the disease than the Page 239 1 medication itself? 2 A. Well, again, I mean I think 3 you're trying to summarize a lot, put a lot of 4 things together. I think we systematically 5 looked at the data, there was no suggestion of 6 such a link. Had there been such a link, a more 7 in-depth evaluation would have been done. But 8 the data were thoroughly evaluated even prior to 9 that time. 10 Q. But the data wasn't evaluated 11 prior to that time to make a determination with 12 respect to any causal connection between Prozac 13 and suicide, was it? 14 A. We didn't carry out the same 15 studies that we subsequently carried out on that 16 issue. 17 Q. I understand that. So 18 wouldn't the answer to my question be yes? 19 A. Well, the indication of your 20 question -- 21 Q. Let me finish my question. 22 Wouldn't the answer be yes, the data had not been 23 examined with the question in mind of whether or 24 not these particular incidences of suicide could Page 240 1 be related to Prozac, until it was raised by the 2 German government? 3 A. I think that's a fair 4 question, assuming, again, Doctor Stark was 5 responsible at that time, and I don't know what 6 all was done at that point. 7 Q. But as far as you know? 8 A. As far as I know. 9 Q. As I understand it from your 10 testimony earlier, when this issue was raised in 11 1984 by the German government by virtue of 12 Exhibit 1, which is a memorandum in which you're 13 a recipient, correct? 14 A. Yes. 15 Q. You don't have any specific 16 recollection of seeing that memo? 17 A. Other than earlier today. 18 Q. Yes, but you don't remember it 19 coming in in 1984? 20 A. No, I don't remember that. 21 Q. And you don't remember reading 22 this in 1984? 23 A. No, I don't remember reading 24 this specific memo in 1984. Page 241 1 Q. Now, Doctor Zerbe, are you an 2 individual that reads most of the information 3 that comes to you in this form, across your desk? 4 A. I would be the type of 5 individual that would, yes, generally read that 6 information. 7 Q. Do you feel you're pretty 8 meticulous in examining, and I don't know whether 9 this is Telex or E-mail or whatever it is, but 10 something that is obviously a corporate 11 communication intended for certain individuals 12 within the corporation? 13 A. Well, I mean I certainly would 14 look at it very carefully, but I'm not a primary 15 addressee on this memo, so I may not have read it 16 as carefully as I would have had it been 17 addressed to me specifically. 18 Q. Well, would you say then that 19 you do carefully read memos addressed to you 20 specifically? 21 A. Well, I certainly try to do my 22 best. 23 Q. Do you -- you don't remember 24 reading this? Page 242 1 A. Well, again, it's been ten 2 years, and it's -- I just don't remember the 3 specific memo. 4 Q. And do you remember being 5 concerned about this issue or all of a sudden 6 here's a bombshell issue that's been dropped on 7 us by the German government with a serious 8 question concerning whether or not there could be 9 a link between Prozac and suicide? 10 A. Well, as I read the memo even 11 today, in looking at it there's, you know, not 12 one issue, there are a number of issues, only one 13 of which was that question. And, so, it wouldn't 14 have necessarily struck me as a bombshell, to use 15 your words. 16 Q. I guess the reason that -- and 17 I think Nancy took my copy, so I'll have to look 18 at yours. 19 A. Okay, that's fine. 20 Q. I guess the reason I was 21 wondering about this is paragraph fourteen says 22 as we've already explained by our Telex to Doctor 23 Zerbe, that's you, of June 1984, we need a 24 careful analysis of suicides and suicide Page 243 1 attempts, the patient by patient symptomatology, 2 severity upon entry into the study, and week by 3 week until the event occurred, dose of 4 Fluoxetine, side effects, et cetera, correct? 5 A. Yes. 6 Q. Then they go on to say this is 7 a very serious issue in the opinion of the BGA, 8 correct? 9 A. Right. 10 Q. It may well be that we will 11 have to recommend concomitant tranquilizer intake 12 for the first two or three weeks in the package 13 literature, correct? 14 A. That's what that memo says, 15 yes. 16 Q. Even though this is item 17 fourteen of a fifteen item Telex, and the issue 18 of suicide is only mentioned in item ten and 19 fourteen, they are at least referring to a 20 previous memo to you concerning this issue, 21 aren't they, Doctor Zerbe? 22 A. Yes. 23 Q. And they are at least saying 24 that this is a very serious issue in the minds of Page 244 1 the British government -- the German government, 2 aren't they? 3 A. They're saying that, yes, 4 that's correct. 5 Q. And they're saying that this 6 may well lead to an approval of Prozac in Germany 7 where there's going to have to be some package 8 literature that has recommendations with respect 9 to concomitant medications, doesn't it? 10 A. I think you read it. Again, I 11 might ask you to repeat the question because I'm 12 not sure in the details what -- 13 MR. SMITH: Read my last question 14 back. 15 (THE COURT REPORTER READ BACK THE 16 REQUESTED TESTIMONY.) 17 A. That's the way I would read 18 the memo, yes. 19 Q. So I would think, since that 20 item is referring to you and referring to another 21 Telex to you, and since that item is referring to 22 whether or not this product is sold in Germany, 23 and whether or not this product is going to be 24 sold in Germany under some type of limitations, Page 245 1 that this would have been some import to you, 2 Doctor Zerbe? 3 A. All of the safety issues were 4 of import to me. 5 Q. So is it or is it not your 6 testimony that you became seriously concerned 7 about this issue at the date of that memo, 8 Exhibit 1? 9 A. Again, I probably would have 10 been concerned at the time of even the previous 11 Telex defining concern as we're interested in 12 looking at all safety issues and thoroughly 13 evaluating them. 14 Q. But that previous Telex 15 doesn't have a concern about all safety issues, 16 that previous Telex was a Telex specifically to 17 you, specifically concerning the issue of 18 suicide, and specifically requesting something be 19 done, wasn't it? 20 A. I don't know what that 21 previous Telex said. 22 Q. That's what it indicates it 23 said there, doesn't it? 24 A. It says that they had Page 246 1 explained by our Telex to Doctor Zerbe that we 2 needed to look at that issue, but it doesn't say 3 that there weren't many other issues as part of 4 that other previous Telex. I don't know what was 5 in the June 8th Telex. 6 Q. Okay. That was going to be my 7 next question. Do you have any recollection of 8 seeing the previous Telex? 9 A. I don't have any recollection, 10 I'm sorry. 11 Q. We've been supplied numerous 12 boxes of correspondence and file material that 13 theoretically you had turned over to the legal 14 department at Lilly with respect to Prozac, but 15 our careful review of that box doesn't indicate 16 that that was ever there. Can you help us as to 17 where that Telex might be? 18 A. I really -- I can't. I mean 19 of course this was again ten years ago. But I 20 routinely -- maybe not at this time because it 21 wasn't -- you know, there wasn't any pending 22 litigation, but certainly after there was any 23 concern about litigation, I routinely passed all 24 of my correspondence to my secretary for copying Page 247 1 and saving. This was prior -- to my knowledge, 2 it was prior to any kind of instructions to that 3 effect, so I don't know what would have happened 4 to the Telex from June 8th. 5 Q. So is it your testimony, 6 Doctor Zerbe, that even before you got the 7 instructions from the legal department at Eli 8 Lilly to preserve your file and to provide 9 periodically copies of your files on Prozac to 10 the legal department, that you had indeed taken 11 steps to preserve all your files prior to that 12 legal memo? 13 A. No, I don't think that's what 14 I said. I'm sorry, I may not have been clear. 15 What I said was that certainly after we received 16 the instruction from the legal department, my 17 standard operating procedure would be without 18 question just to give it to my secretary to keep 19 a copy of any correspondence which I received. 20 Prior to the time we received that instruction, I 21 didn't have that systematic approach to save such 22 memos. 23 Q. What would normally have 24 happened to that, what did you normally do before Page 248 1 you got those instructions with respect to your 2 normal files? 3 A. Well, what I probably would 4 have done would -- I would have taken the memo, 5 and in a meeting with Doctor Stark we would have 6 defined what we needed to do to address that 7 problem. 8 Q. Do you recall such a meeting 9 with Doctor Stark in connection with that -- 10 A. I don't recall a specific 11 meeting. 12 Q. Memo -- 13 A. I don't recall a specific 14 meeting with regard to that memo. I think you 15 asked me in general what I would do, and that's 16 what I'm saying I would generally do. But I 17 don't know specifically in this situation. 18 Q. My question is what would you 19 generally do with the document itself, would you 20 have left it with Doctor Stark or would you have 21 brought it back and put it in a file you 22 maintained? 23 A. I typically probably would 24 have kept it in a file that I maintained on this Page 249 1 issue. 2 Q. What issue, the issue of -- 3 A. Suicide. 4 Q. The issue of Prozac and 5 suicide? 6 A. Yes. And it would either end 7 up in a file like that or a file that kept all my 8 work with Doctor Stark. 9 Q. Do you recall having a Prozac 10 suicide file? 11 A. I don't recall specifically 12 having a Prozac suicide file, although it's 13 likely that such a file existed at one point as 14 this was an active issue. 15 Q. And you think you would have 16 segregated documents you received concerning this 17 issue and kept them within that one file? 18 A. Again, I may have. I mean 19 you're asking me to describe how I would usually 20 deal with a situation, a question that came up, 21 and I'm just describing that. 22 Q. Did Lilly have a document 23 retention policy in place in 1984? 24 A. I really don't know what Page 250 1 Lilly's policy was in 1984. 2 Q. If they had a document 3 retention policy, you weren't aware of what it 4 was? 5 A. Not for items such as routine 6 correspondence, I mean there was certainly a 7 document retention policy with regard to 8 regulatory documents, things submitted to 9 regulatory agencies. 10 Q. That would be a policy that 11 had been promoted by the regulatory department 12 itself, would it not? 13 A. Yes. 14 Q. And my question is, did Lilly 15 have a separate document retention policy where 16 there was a corporate directive that all 17 documents are to be kept for either the length of 18 a particular project or if the project was over, 19 destroyed within say five years or something of 20 that nature? 21 A. I was not aware of any 22 specific document retention policy that dealt 23 with these kinds of communications, specific 24 Telexes or verbal communications that you had Page 251 1 notes or notes to file or that kind of thing. 2 The only one that was the regulatory documents, 3 or in cases of specific litigation, they were 4 sometimes requested to retain files. 5 Q. How did you go about closing a 6 file? 7 A. I mean -- I guess you could 8 ask that question to anyone. Periodically one 9 goes through and tosses files that are no longer 10 relevant. 11 Q. Okay. That's my question, did 12 you have the ability at Lilly if you were through 13 with a file and you needed more space, just for 14 that reason, for instance, if you had the ability 15 to exercise your discretion to pitch it in the 16 trash can and it would be picked up by the 17 janitor at the end of the day? 18 A. Unless it fell under the 19 limitations that I mentioned before, yes. 20 Q. Well, we got a little bit off 21 the subject, but the point is you don't know what 22 happened to the early June, 1984 Telex? 23 A. No. 24 Q. And you don't recall any Page 252 1 specific thing you might have done in response to 2 the early June, 1984 Telex? 3 A. I don't recall any specific 4 thing I might have done. 5 Q. Do you recall specifically 6 what you did in response to this particular 7 document, Exhibit 1? 8 A. No, I don't know, I can't tell 9 you what specific response there was to Exhibit 10 1. 11 Q. All right. It says on point 12 fourteen that we need a careful analysis of 13 suicide and suicide attempts, patient by patient, 14 symptomatology, severity and entry into the study 15 week by week until the event occurred, dose of 16 Fluoxetine, side effects, et cetera, right? 17 A. That's what it says. 18 Q. Could it have been that either 19 you or someone to whom that memo was directed 20 would have compiled that information that was 21 being requested out of Germany? 22 A. I think the information -- 23 this would have been the beginning of the review 24 of data for response to the BGA, looking at the Page 253 1 suicides and rates and so forth, because I think 2 we talked about it before. 3 Q. My question is, can we say 4 that there may be some link between this June, 5 '84 memo, Exhibit 1, Re.: Fluoxetine 6 registration in Germany, and this data that is 7 reviewed in the April, 1985 meeting where they're 8 talking about the original documentation 9 submitted March, 1984, the analysis of pooled 10 studies, Fluoxetine versus Imipramine versus 11 placebo, protocol number twenty-seven, submitted 12 October '84? 13 A. It's very difficult to leap 14 from this to that in terms of temporally. 15 Q. I have some question about 16 that myself because Exhibit 1, what we have found 17 to be the original document that we have found 18 concerning the German suicidality issue is dated 19 June 26, 1984, correct? 20 A. Exhibit 1 is dated June 26, 21 1984, yes. 22 Q. And do you know of any other 23 original memo other than possibly this Telex of 24 June 8, 1984? Page 254 1 MR. MYERS: On the same subject? 2 MR. SMITH: On the same subject, yes. 3 A. I don't know of any other such 4 memo. 5 Q. You see in this meeting where 6 apparently there was a lot of discussion over the 7 clinical trial data, they were reviewing 8 documentation sumitted March 1, 1984, but the 9 meeting was occurring a year later. So I don't 10 know whether it was documentation submitted by 11 Lilly to Germany or whether that was some other 12 documentation submitted to some other entity. Do 13 you follow what my inquiry is? 14 A. Well, I don't entirely 15 understand what you're asking. 16 Q. Well, I guess it's do you have 17 any idea what the documentation was that they 18 were reviewing of March 1, 1984? 19 A. I mean any idea could be 20 purely speculation, but I really don't have any 21 idea other than the temporal relationships to 22 base any thoughts on. 23 A. Obviously we know they made an 24 analysis that they had reviewed data which Page 255 1 consisted of an analysis of pooled studies, 2 Fluoxetine versus Imipramine versus placebo, 3 protocol number twenty-seven, submitted October 4 25, '84, don't we? 5 A. They did review that one, yes, 6 protocol twenty-seven, at least according to this 7 document. 8 Q. Do you recall receiving 9 Exhibit 3? 10 A. Do I recall. I think I 11 already responded I don't recall receiving this 12 specific document. 13 Q. Do you recall ever seeing the 14 twenty-one page opinion that the expert in 15 Germany, Doctor, I believe his name was, 16 Herrmann, had made? 17 A. I don't ever recall seeing 18 that. 19 Q. What was your job title in 20 April of 1985? 21 A. In April of 1985, I was the 22 director for clinical investigation in regulatory 23 affairs for the neuro endocrine division. 24 Q. So this would have certainly Page 256 1 been something that fell under your purview? 2 A. Well, actually probably not 3 technically because this -- I was responsible 4 really only for the U.S. part of the -- 5 technically the U.S. part of the organization. 6 We communicated a lot, but this was technically a 7 German issue, so I may or may not have received 8 it. 9 Q. All right. You don't have any 10 recollection of receiving it, though -- 11 A. No, I don't have any -- 12 Q. -- as you sit here today? 13 A. No, I don't have any 14 recollection of receiving it. 15 Q. Who would have been the 16 individual primarily responsible in connection 17 with this issue? 18 A. Well, there -- how do you 19 define primarily responsible? I mean Doctor 20 Schenk here would have been closest to that 21 issue. 22 Q. All right. He would have been 23 closest to the issue in Germany? 24 A. She would have been, yes. Page 257 1 Q. She would have been closest to 2 the issue in Germany, correct? 3 A. That's right. 4 Q. Who was her boss? 5 A. I think she reported to Doctor 6 Weber at that time. 7 Q. Weber, is that what we've been 8 calling Weber? 9 A. Yes, Weber, Weber. There's 10 more than one Weber. 11 Q. Hans -- 12 A. Hans Weber, yes. 13 Q. We didn't go to Europe, so we 14 didn't learn the true pronunciation. All right. 15 Who was Doctor Weber's boss? 16 A. Well, Doctor Weber -- I don't 17 know how you capture that, but -- 18 Q. She's going to spell it the 19 same way however we pronounce it. 20 A. -- would have reported to the 21 affiliate management in Germany. 22 Q. Okay. Who was the affiliate 23 manager in Germany at that time? 24 A. I don't know, to be honest Page 258 1 with you, I mean there were a series of different 2 ones and I don't know who exactly was in 1985. 3 Q. You eventually became the 4 manager of all European affiliates, did you not? 5 A. Well, I was responsible for 6 coordinating their activities, but they didn't 7 report to me, all those affiliates didn't report 8 to me. 9 Q. Who did the affiliate heads 10 report to in Indianapolis? 11 A. Well, you're getting into 12 structures of Lilly International, and I don't 13 know how all of that organizational structure was 14 set up. At that time, Doctor Perelman was head 15 of Lilly International, as I recall, but I'm not 16 sure how involved Doctor Perelman -- it would 17 have been many steps removed from Doctor 18 Perelman, and I just don't know all those steps. 19 (DISCUSSION OFF THE RECORD.) 20 Q. I was asking you the question 21 of who is the most senior individual listed on 22 Exhibit 3 or the individual who had most 23 management responsibility might be a better way 24 to put it? Page 259 1 A. Well, those may be two 2 different questions. 3 Q. Okay, then answer both. 4 A. The two highest level people 5 on here that I would say at this time, and I'm 6 not sure which one was higher -- well, I think it 7 was either Doctor Weinstein or Doctor Harrill -- 8 or Mister Harrill. I think those were the two -- 9 oh, well, I don't know. But -- 10 Q. Do you see somebody else on 11 there that may be a bigger dog? 12 A. Well, I don't know a bigger 13 dog. 14 MR. MYERS: He's speaking Texas now. 15 A. No, I think probably those 16 were probably the two. 17 Q. Doctor Zerbe, would you be 18 third on the list? 19 A. Would I be third on the list, 20 on this list? 21 Q. In connection with management 22 responsibility and seniority at that time? 23 A. No. 24 Q. You said Harrill and who? Page 260 1 A. Doctor Weinstein. 2 Q. Doctor Weinstein. At the time 3 that you -- when were you the manager of 4 worldwide regulatory affairs? 5 A. Really not until shortly 6 before I left. 7 Q. When was that? 8 A. From about March of '93 to 9 July of '93. 10 Q. Had you received this document 11 in March of 1993 as manager of worldwide 12 regulatory affairs, would you have instructed 13 that this document be filed or submitted to the 14 Food and Drug Administration? 15 A. I'm sorry, which document? 16 Q. Exhibit 3, the April, 1985 17 memo. 18 A. This does not appear to be the 19 type of document that would have been appropriate 20 for submission to the FDA. 21 Q. All right. So is the answer 22 to my question no, I would not have instructed 23 that it be submitted to the Food and Drug 24 Administration? Page 261 1 A. Well, again, I mean I think it 2 would depend on the situation. We -- I mean it's 3 not a trivial point, it's an important point. We 4 frequently submitted things to the FDA for their 5 information if we felt that it was wise to do, 6 whether we were required to or not, so I think it 7 would depend on the situation. But in looking at 8 this, it wouldn't have been something we would 9 have immediately submitted to the FDA. 10 Q. All right. So is the answer 11 to my question that if this document had been 12 sent to you when you had responsibility for 13 making the decision concerning whether or not it 14 be filed with the Food and Drug Administration, 15 that is when you were the director of worldwide 16 regulatory affairs, would you have submitted -- 17 would you have instructed that it be submitted to 18 the Food and Drug Administration in the United 19 States? 20 A. No, I don't believe I would 21 have. 22 Q. You notice that that document 23 contains mention of a twenty-one page expert 24 report which raises questions concerning the Page 262 1 suicidality link between Prozac and -- the link 2 between Prozac and suicidality, correct? 3 A. It does mention that, yes. 4 Q. Would you have instructed that 5 that twenty-one page memoranda or opinion from 6 the independent expert that had been hired by 7 Lilly be filed with the Food and Drug 8 Administration for their consideration? 9 A. I think it would depend on 10 whether there was anything that was new or 11 alarming that came out of that twenty-one page 12 document. 13 Q. Well, the Lilly employees 14 summarize safety considerations mentioned by that 15 document on page two of the exhibit, do they not? 16 A. Yes. 17 Q. And it indicates that there 18 was a high number of suicides on Fluoxetine 19 versus Imipramine, does it not? 20 A. I'm not sure that says exactly 21 that. 22 Q. But that's the substance of 23 what it says, isn't it? 24 MR. MYERS: I object to the form, the Page 263 1 document says what it says, it speaks for itself. 2 Q. Okay. I'll come over there 3 and read what it says. 4 A. I don't know which thing 5 you're talking about. 6 Q. It says still not resolved is 7 the fact that suicide attempts have been observed 8 more frequently on Fluoxetine as compared to 9 Imipramine. And then it says that incidence of 10 suicide was abnormally high. So I'm talking 11 about the terms more frequent and abnormally 12 high, and to be fair with you I'll say abnormally 13 low of the comparators. 14 A. And then really to be fair to 15 us, I think it's important to put the whole 16 statement in context. It says still not 17 resolved, which I think is a very important point 18 with regard to the decision to submit or not to 19 submit, the fact that suicide attempts have been 20 observed more frequently on Fluoxetine as 21 compared to Imipramine, parentheses, and this is 22 an important point as well, only epidemiologic 23 data or literature on other antidepressants may 24 help to identify whether it happened by chance Page 264 1 that that incidence of suicide attempts was 2 abnormally high on Fluoxetine or abnormally low 3 under comparators, end parentheses. 4 Q. To be fair to both of us -- 5 A. Yes. 6 Q. -- Doctor Zerbe, the import of 7 that paragraph could have several connotations, 8 could it not, it could be read in a couple of 9 different ways, couldn't it? 10 A. I think -- you're right, it's 11 very hard to reconstruct exactly what the 12 thoughts were at that time. 13 Q. There could be, by looking at 14 that document, especially in light of the fact 15 that you already knew that Germany was concerned 16 about this issue, it could be that that 17 twenty-one page document memo raised serious 18 safety considerations, couldn't it, whether they 19 be resolved or unresolved? 20 A. Well, I think you're putting 21 pieces of information together and -- 22 Q. Yes, I am, I sure am. And I 23 think it's -- 24 MR. MYERS: Let him finish, Paul. Page 265 1 Q. I think it's that I have that 2 ability to do that because I'm reconstructing 3 something -- trying to reconstruct something that 4 occurred ten years ago, and my question really is 5 if you look at those two things together, can you 6 say that this is information, this twenty-one 7 page memorandum, that the Food and Drug 8 Administration should have had? 9 A. Even as I look at the 10 information together in the way that you 11 constructed it, I don't feel that it's likely 12 that this twenty-one page document would have 13 been something that would have been submitted to 14 the FDA in its pure form. That isn't to say that 15 we would not have told the FDA and shared the 16 information with the FDA about the concern that 17 the BGA might have had. But that doesn't mean 18 that we would have submitted exactly that 19 document, it wouldn't have been the kind of 20 document they would have wanted to see. 21 Q. Well, isn't the Food and Drug 22 Administration concerned with documents 23 reflective of the safety of drugs under approval 24 consideration? Page 266 1 A. The FDA is very concerned 2 about the safety, and they would very much like 3 to receive data that are meaningful. 4 Q. All right. And wasn't Prozac 5 at this time, on both Exhibit 1 and 3, under 6 consideration by the United States Food and Drug 7 Administration for approval? 8 A. Yes. 9 Q. And weren't there ongoing 10 clinical trials at that time? 11 A. I believe there were ongoing 12 clinical trials at that time. 13 Q. And doesn't Exhibit 3, this 14 April, 1985, mention a specific protocol number 15 twenty-seven that was a multi-center clinical 16 trial done in whole or in part in the United 17 States of America? 18 A. I don't know where protocol 19 twenty-seven was done, I don't know what protocol 20 twenty-seven is. 21 Q. Let me tell you then, that it 22 is a multi-center study that was submitted by Eli 23 Lilly and Company to the Food and Drug 24 Administration that was characterized both by Eli Page 267 1 Lilly and Company and the Food and Drug 2 Administration as a pivotal trial. Will you take 3 that assumption? 4 A. Yes. But then it had already 5 been submitted to the FDA. 6 Q. Yes. 7 A. Okay. 8 Q. And this twenty-one page memo, 9 I would assume, wouldn't it be a fair assumption 10 that this was an analysis of a safety problem 11 that this particular expert that Lilly had hired 12 had found in that protocol? 13 MR. MYERS: Well, let me object to the 14 form because I think now you've mischaracterized 15 what's in the memo and what he's earlier said. 16 Go ahead and answer if you can. 17 A. Could you repeat the question? 18 Q. I can't, but she can read it 19 back. 20 (THE COURT REPORTER READ BACK THE 21 REQUESTED TESTIMONY.) 22 A. I don't think that is a safe 23 assumption, that's not the way that I read this 24 memo. Page 268 1 Q. Couldn't the memo be read that 2 way, though? 3 A. I really don't think so. 4 Q. Okay. You don't think any 5 reasonable person could conclude from reading 6 that memo that there might be a safety problem 7 here? 8 A. I don't think that was the 9 question you asked. 10 Q. Do you think any reasonable 11 person reading that memo could conclude that 12 there's a safety problem here? 13 A. It's impossible for me to 14 speculate what was in the twenty-one page memo, 15 except what's written here which describes both 16 efficacy and safety. And it includes things 17 other than protocol twenty-seven. 18 Q. I understand that. But it 19 certainly has to do with safety because it 20 designates safety as a consideration, does it 21 not? 22 A. It was an evaluation of 23 efficacy and safety. 24 Q. Apparently this twenty-one Page 269 1 page memo broke down this analysis of this data 2 and looked at the analysis from an efficacy 3 standpoint, didn't it, from what it looks like 4 there? 5 A. Well, my impression of this is 6 a description of an outside expert evaluating two 7 pieces of data, neither of which I'm directly 8 familiar with -- 9 Q. I understand that. 10 A. -- and making some statements. 11 Q. Uh-huh. 12 A. To my knowledge, all of the 13 data which this outside expert reviewed had 14 already been submitted to the Food and Drug 15 Administration. 16 Q. Okay, all right. So you're 17 going to leave it up to the Food and Drug 18 Administration to make their characterization of 19 whether or not this data presented a safety 20 problem? 21 A. Well, if there were something 22 new, then -- new piece of data, new analysis, 23 then that might be cause to submit it, but 24 there's no indication from what I read here that Page 270 1 there was anything new. 2 Q. Wasn't the opinion a new 3 opinion about this data? 4 A. But we don't necessarily 5 report opinions, Everybody that comes forward 6 with an opinion to share every opinion with every 7 regulator. We deal with facts and the synthesis 8 of those facts. 9 Q. All right. Do I understand 10 it, Doctor Zerbe, that it was Lilly's position 11 and your position, when you were at Eli Lilly and 12 Company, that if you had some data that contains 13 safety information, and you hired an expert to 14 review that data, and that expert made some 15 comments with respect to the safety information, 16 that this would not be information that Eli Lilly 17 and Company would pass on to the Food and Drug 18 Administration? 19 A. I think you misunderstood what 20 I said. 21 Q. Answer my question yes or no. 22 A. You'll have to repeat the 23 question. 24 MR. SMITH: Repeat it, please. Page 271 1 (THE COURT REPORTER READ BACK THE 2 REQUESTED TESTIMONY.) 3 A. I think I'm going to have to 4 ask you to restate the question, that's an 5 impossible question to sort through. Can you 6 crystalize the question for me? 7 Q. You got safety information. 8 A. Yes. 9 Q. Data, all right? 10 A. Data, yes, whatever, I didn't 11 mean to correct you. I was actually repeating, I 12 wasn't correcting, I'm sorry. 13 Q. You're not going to hurt my 14 feelings, don't worry. 15 A. It was not meant to be that 16 way. 17 Q. I didn't take it that way. 18 You've got safety data, you've got data, and that 19 data concerns the safety of a particular drug 20 under consideration, all right? 21 A. Right. 22 Q. And Lilly hires an expert to 23 review that data, and that expert reviews that 24 data and makes a comment or renders an opinion Page 272 1 concerning the safety aspects of that data that 2 Lilly has. Is Lilly required or is it Lilly 3 policy to submit that opinion that that expert 4 has to the Food and Drug Administration? 5 A. I don't know that Lilly has a 6 policy other than to fully comply with all 7 regulations related to reporting safety data. We 8 would certainly report the data and make the FDA 9 aware of the information. The interpretation of 10 those data may be reported as from an outside 11 expert, as a report from that expert, or it may 12 be combined with the opinions of other experts 13 and reported as a summary. But the policy of 14 Lilly would be to keep the FDA fully and 15 accurately informed about any findings. Whether 16 this twenty-one page document contributed 17 anything new, I can't say. 18 Q. I understand that. And 19 whether it's new, old or indifferent, my question 20 simply is, is this an opinion concerning data 21 that Lilly has and the Food and Drug 22 Administration has, and this is an opinion 23 concerning the safety of this product. Does 24 Lilly submit that opinion to the Food and Drug Page 273 1 Administration, regardless of whether or not the 2 Food and Drug Administration has the underlying 3 data? 4 MR. MYERS: Well, that's been asked 5 and answered, but answer it again. 6 A. Let me try to -- basically I 7 repeat the same thing that I said, which is that 8 we would be certain that any data would be 9 submitted to the FDA, and that information, 10 opinions, would be shared with the FDA, whether 11 it was in the form of the report that came from 12 the outside expert or whether that report was 13 synthesized with other records to provide a more 14 global assessment of that issue. Ultimately that 15 information would be shared with the FDA. I 16 don't know whether this document contributed 17 anything new. 18 Q. I understand that. 19 A. Okay. 20 Q. And that's not the point of 21 argument. Let me modify my question a little bit 22 and maybe I can get a little more direct answer 23 from you. 24 A. Okay. Page 274 1 Q. I want you to make two 2 assumptions. I want you -- or maybe a number of 3 assumptions. I want you to make the assumption 4 that both Lilly and the Food and Drug 5 Administration have that data, all right, and 6 that you have Lilly that has hired only one 7 expert to review that data, and that that expert 8 has come to an opinion and rendered a written 9 opinion concerning safety aspects of that data. 10 You just have one expert. Will Lilly submit that 11 expert opinion to the Food and Drug 12 Administration? 13 A. If it represented some 14 significant new finding or insight, then we would 15 most likely submit that information for 16 information. 17 Q. Is that a requirement that 18 you're adding, that it must add some significant 19 new information or insight? 20 A. Well, if you're asking the 21 question can I confirm, is it Lilly policy to 22 submit every expert opinion to the FDA, I don't 23 know that it is the policy to do that. 24 Q. All right. Let me ask you Page 275 1 what your policy was when you were the individual 2 charged with that responsibility as director of 3 worldwide regulatory affairs. 4 A. I think I stated the policy by 5 which I would operate, and I can restate it if 6 you'd like. 7 Q. Well, can you state it in 8 light of the hypothesis that I've given you, that 9 is that you have both the FDA and Lilly with the 10 data, and that you have only one opinion, so 11 you're not going to submit it later on once 12 you're going to get a bunch of opinions. You 13 only have one opinion, and the opinion and the 14 data has safety import or safety comments, would 15 you submit that to the Food and Drug 16 Administration? 17 A. My personal policy would be 18 that the information contained in that report 19 would be shared with the FDA, either in the form 20 of the original summary by the outside expert or 21 synthesized as part of a more global issue. And 22 that's not only outside experts, I mean you said 23 we only had one outside expert, but synthesized 24 as part of a bigger picture, that information Page 276 1 would be shared with the FDA if it contained 2 significant new findings, something new. 3 Q. See, that's where I'm have -- 4 I followed your answer right down to the very 5 last, until you said if it contained significant 6 new findings, and you see, I'm wondering whether 7 or not that's the key on whether or not you're 8 going to pass this information on, is that you're 9 making a determination concerning whether or not 10 these findings are significant and whether or not 11 they're new. 12 A. Well, I think, again, the 13 approach that I would routinely take is, and I 14 think Lilly has always taken, was to be very open 15 and share more information with the FDA. The 16 exception that I was trying to cite was that the 17 FDA is not necessarily interested in the, you 18 know, fifteenth outside expert review of a 19 product in the Netherlands when it contains 20 nothing more than what they already know, there's 21 not anything new in it, they're not interested in 22 receiving that information. But we always took a 23 very conservative approach in submitting 24 information. Page 277 1 Q. Okay. Let me ask you this: 2 Was the fact that suicide attempts were observed 3 more frequently on Fluoxetine as compared to 4 Imipramine significant in your opinion? 5 A. Well -- 6 Q. Would it have been significant 7 at the time? 8 A. I mean, again, you have to 9 read what this says. It says it's still not 10 resolved is the fact that suicide attempts have 11 been observed. It's a preliminary observation. 12 Q. Is it preliminary because -- 13 see, what I'm wondering about is because a year 14 earlier or ten months earlier, you had already 15 been put on notice that the BGA considered this 16 a, quote, very serious issue. Do you understand 17 what I'm saying? 18 A. Well, it was a serious issue 19 according to the BGA, but I'm not sure what they 20 base that conclusion on, and it may be nothing, 21 you know. 22 Q. Well, now you know that you've 23 hired an independent expert and your independent 24 expert has found a situation where you have a Page 278 1 higher incidence of suicide on Fluoxetine than 2 you do on Imipramine, right? 3 A. I can still read this as still 4 not resolved, meaning these are preliminary 5 observations, and -- 6 Q. I'm -- 7 MR. MYERS: Let him finish, Paul. 8 A. We wouldn't necessarily 9 present preliminary observations unless it 10 represented, you know, a big safety issue. 11 MR. DOWNEY: Move to strike as 12 nonresponsive and utterly evasive. 13 MR. MYERS: Overruled. 14 Q. You knew at least a year 15 earlier that the BGA had viewed the question of 16 suicide as a serious issue, didn't you? 17 A. Again, I would have to look at 18 the dates. These are less than one year apart. 19 Q. What is it, ten months? 20 A. Yes, I mean you have the 21 dates. April '85 and June of '84. 22 Q. So even closer in time you 23 knew that the BGA considered this issue of 24 suicide a serious issue? Page 279 1 A. Well, this is again -- I think 2 you pointed out or somebody has pointed out 3 during the day, this is in the words of somebody 4 else. I don't really know what the BGA 5 considered, and it's, as best I can determine, 6 almost third removed because it's a review of a 7 review. 8 Q. But it's a review by Lilly 9 personnel there in Exhibit 3, isn't it? 10 MR. MYERS: Let me object to the form, 11 that mischaracterizes the memo and what he said. 12 Whose review? 13 MR. SMITH: The memo is -- well, he 14 said it's a review of a review of a review, but 15 the author is a Doctor Johanna Schenk, isn't it? 16 A. Yes, that's true. 17 Q. And she's a Lilly employee, 18 correct? 19 A. Yes. 20 Q. And the memo, the twenty-one 21 page expert opinion, is an individual who was 22 hired by Lilly to review this matter, wasn't it, 23 wasn't he, Doctor Herrmann? 24 A. I don't know whether it was Page 280 1 Doctor Herrmann or not, I don't know who it was 2 nor do I know who hired that person. 3 Q. Well, I'll help you then if 4 you don't know that. 5 A. Okay. 6 Q. To make Professor Blank, then 7 if we turn over to page three, it says Herrmann's 8 opinion, all right. Then you say Professor Blank 9 left an opinion of twenty-one typewritten pages. 10 Don't you think it's reasonable to conclude that 11 the name that was blacked out was Mister Herrmann 12 or Doctor Herrmann? 13 A. I really don't know what's 14 reasonable to conclude from the memo. 15 Q. Obviously, we're going around 16 and around to a certain extent here. I guess, 17 you know, I'll drop it at this: Did you 18 consider, in '84 and '85, when you received these 19 memos, that the issue of suicide and Prozac was a 20 serious concern in Germany? 21 A. Are you saying was it a 22 serious concern from my perspective? 23 Q. Yes. 24 A. All safety issues were serious Page 281 1 concerns. 2 Q. So would you be able to answer 3 that question yes then? 4 A. Yes. 5 Q. All right. 6 MR. MYERS: Paul, can we stop, it's 7 after 5:00 o'clock. 8 MR. SMITH: Okay. 9 (THE WITNESS WAS EXCUSED.) Page 282 1 COMMONWEALTH OF KENTUCKY ) 2 : ss COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 DR. ROBERT ZERBE 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 9TH DAY OF 19 JUNE, 1994. 20 MY COMMISSION EXPIRES MARCH 10, 1994. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 283 1 E R R A T A S H E E T 2 3 STATE OF ) : SS 4 COUNTY OF ) 5 6 I, DR. ROBERT ZERBE, THE UNDERSIGNED 7 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 8 OF MY DEPOSITION AND WITH THE CHANGES NOTED 9 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 10 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 11 THE 13TH DAY OF MAY, 1994 AT THE TIME AND PLACE 12 STATED THEREIN. 13 PAGE NO. LINE NO. CHANGE REASON Page 284 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. ROBERT ZERBE 10 SWORN TO AND SUBSCRIBED BEFORE ME THIS 11 _____ DAY OF __________, 1994. 12 _____________________________ NOTARY PUBLIC, STATE OF 13 AT LARGE Page 285 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Page 286 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Page 287 1 DR. ROBERT L. ZERBE...............................11 2 DIRECT EXAMINATIONBY MS. ZETTLER:.................12 3 EXAMINATIONBY MR. SMITH:.........................225 4 COMMONWEALTH.....................................283 5 (QUESTION CERTIFIED.).............................20 6 PLAINTIFFS' EXHIBIT NO. 1.........................63 7 PLAINTIFFS' EXHIBIT NO. 2.........................85 8 PLAINTIFFS' EXHIBIT NO. 3.........................94 9 PLAINTIFFS' EXHIBITS 3 AND 4.....................133 10 PLAINTIFFS' EXHIBIT NO. 5........................163 11 PLAINTIFFS' EXHIBIT NO. 6........................171 12 PLAINTIFFS' EXHIBIT NO. 7........................183 13 PLAINTIFFS' EXHIBIT NO. 8........................186 14 PLAINTIFFS' EXHIBIT NO. 9........................192 15 PLAINTIFFS' EXHIBIT NO. 10.......................221 16 E R R............................................284 17 18 Page 288