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. MAX TALBOTT 11 DATE: APRIL 19 AND 20, 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. MAX TALBOTT, TAKEN AT 2 THE OFFICE OF BAKER & DANIELS, 300 NORTH MERIDIAN 3 STREET, SUITE 2700, INDIANAPOLIS, INDIANA 46204, 4 ON APRIL 19 AND 20, 1994; SAID DEPOSITION TAKEN 5 PURSUANT TO NOTICE IN ACCORDANCE WITH THE RULES 6 OF CIVIL PROCEDURE. 7 * * * * * * * * * * 8 A P P E A R A N C E S 9 10 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 11 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 12 PAUL SMITH 13 COUNSEL FOR PLAINTIFFS 745 CAMPBELL CENTER 2 14 8115 NORTH CENTRAL EXPRESSWAY DALLAS, TEXAS 75206 15 LAWRENCE J. MYERS 16 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 17 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 18 ATLANTA, GEORGIA 30308-3243 MARGARET M. HUFF 19 ELI LILLY AND COMPANY LILLY CORPORATE CENTER 20 INDIANAPOLIS, INDIANA 46285 Page 8 1 ALLISON SPRUILL 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 Page 9 1 I N D E X 2 3 DEPOSITION OF DR. MAX TALBOTT 4 5 DIRECT EXAMINATION BY MR. SMITH 11 6 DIRECT EXAMINATION BY MS. ZETTLER 309 7 8 CERTIFIED QUESTION 262 9 10 CERTIFICATE 624 11 ERRATA 625 12 EXHIBITS 13 PLAINTIFFS' EXHIBIT NO. 1 40 PLAINTIFFS' EXHIBIT NO. 2 70 14 PLAINTIFFS' EXHIBIT NO. 3 166 PLAINTIFFS' EXHIBIT NO. 4 200 15 PLAINTIFFS' EXHIBIT NO. 5 229 PLAINTIFFS' EXHIBIT NO. 6 292 16 PLAINTIFFS' EXHIBIT NO. 7 303 PLAINTIFFS' EXHIBIT NO. 8 419 17 PLAINTIFFS' EXHIBIT NO. 9 441 PLAINTIFFS' EXHIBIT NO. 10 454 18 PLAINTIFFS' EXHIBIT NO. 11 460 PLAINTIFFS' EXHIBIT NO. 12 526 19 PLAINTIFFS' EXHIBIT NO. 13 535 PLAINTIFFS' EXHIBIT NO. 14 539 20 PLAINTIFFS' EXHIBIT NO. 15 553 PLAINTIFFS' EXHIBIT NO. 16 586 21 PLAINTIFFS' EXHIBIT NO. 17 606 Page 10 1 MR. MYERS: Put this on the record. I 2 assume this deposition, like the depositions of 3 Doctors Wong and Fuller last week, is being taken 4 in the same cases as those depositions and with 5 respect to your Texas state court cases and your 6 state court case in Kansas, I understand that we 7 have agreed for purposes of this deposition and 8 the other depositions that have been noticed for 9 this month to allow the multi-district 10 confidentiality order to govern. Correct? 11 MR. SMITH: Correct. 12 MR. MYERS: I will get you that other 13 style. 14 MR. HARRIS: We agree as well. 15 MR. MYERS: Thank you. You can 16 reswear him, he's still under oath. I don't 17 care, whatever your pleasure is. 18 MR. SMITH: Swear him again. 19 * * * * * * * * * * 20 COMES DOCTOR MAX TALBOTT, CALLED BY 21 THE PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, 22 WAS DEPOSED AND TESTIFIED AS FOLLOWS: 23 DIRECT EXAMINATION 24 BY MR. SMITH: Page 11 1 Q. Doctor Talbott, we met and we 2 have begun and ended your deposition on a couple 3 of occasions, or begun and adjourned your 4 deposition on a couple of occasions. I would 5 like to remind you that we're continuing to take 6 your deposition this morning in these 7 Prozac-Lilly cases, and that you're still under 8 oath and that what you say today here can and 9 will be used as evidence in the trial of these 10 cases. Do you understand that? 11 A. I understand that. 12 Q. Again, I think as I cautioned 13 you earlier, if I ask you a question that you 14 don't understand, would you please let me know? 15 A. I will, sir. 16 Q. Otherwise, if you give me an 17 answer, I'm going to assume that you understood 18 my question and we're on the same speech wave 19 length, at least, all right? 20 A. Fine. 21 Q. A brief background. As I 22 understand it, you were the head of regulatory 23 affairs at Eli Lilly and Company from when to 24 when? Page 12 1 A. My title is -- was Director of 2 Medical regulatory affairs, that was from 1988 3 until 1993, and then in May of 1993, I became 4 Director of Worldwide regulatory affairs. 5 Q. Prior to 1988, you were the 6 manager of regulatory affairs? 7 A. I was manager of regulatory 8 affairs for one year, Mister Smith, 1987 to 1988. 9 Q. And before 1987, what was your 10 job description? 11 A. I was a regulatory scientist. 12 Q. And what years were you a 13 regulatory scientist? 14 A. I believe, that title started 15 in 1985, if memory serves me correctly. 16 Q. And before 1985? 17 A. I believe, the title then was 18 regulatory associate. 19 Q. And what years were you the 20 regulatory associate? 21 A. Since I have been at Lilly. I 22 started in 1982. 23 Q. Prior to being with Lilly, you 24 had been with the United States Food and Drug Page 13 1 Administration, is that correct? 2 A. That is correct, sir. 3 Q. And part of your duties with 4 the U.S. Food and Drug Administration had to do 5 with dealing with private companies such as Lilly 6 or any other pharmaceutical manufacturer in their 7 compliance with FDA regulations concerning what 8 was necessary with respect to whatever product 9 they were either marketing or proposed to market, 10 is that right? 11 A. Actually it was device 12 companies, Mister Smith, not pharmaceutical. 13 Q. I understand that, it was 14 medical devices that you were dealing with, but 15 you were dealing with private firms who were 16 attempting to secure FDA approval for these 17 devices or comply with FDA regulations, 18 postapproval of the devices, is that right? 19 A. That's correct, sir. 20 Q. And how long were you with the 21 FDA? 22 A. From 1977 until 1982. 23 Q. And since 1982, I assume up 24 until 1993, at least, you dealt on a day-to-day Page 14 1 basis with the Food and Drug Administration? 2 A. That's correct, sir. 3 Q. In connection with your work 4 at Eli Lilly and Company? 5 A. That's correct, sir. 6 Q. And that work that you did for 7 Lilly since 1982 has been in assisting Eli Lilly 8 and Company in complying with Food and Drug 9 Administration regulations with respect to the 10 pharmaceutical industry, is that correct? 11 A. In part, yes, that's part of 12 my job. 13 Q. That -- those duties involved 14 Prozac to a large extent, did they not? 15 A. Starting in 1985, that's 16 correct, sir. 17 Q. Once you became a regulatory 18 scientist, you were dealing on a regular basis 19 with the Food and Drug Administration in 20 connection with the approval of Prozac as a drug 21 to be consumed by citizens of the United States? 22 A. That's correct, sir. 23 Q. And after 1985 -- or by 1985, 24 when you became a regulatory scientist, your work Page 15 1 dealt exclusively with Prozac, did it not? 2 A. I had other drugs under my 3 responsibilities, but I dealt with Prozac, yes. 4 Q. Didn't there come a period of 5 time that you were just dealing with Prozac in 6 connection with securing FDA approval? 7 A. It was the vast majority of 8 the work. I had responsibilities for some other 9 drugs, but Prozac was the vast majority of the 10 work. 11 Q. Ninety-five percent of your 12 work was -- 13 A. A lot. I'm not sure if 14 ninety-five percent, but a lot, certainly. 15 Q. Most days you would spend 16 almost all day working on matters in connection 17 with securing compliance with Lilly with Food and 18 Drug Administration regulations? 19 A. That's correct. 20 Q. And since 1985, you've been in 21 contact on a regular basis with members of the 22 Food and Drug Administration in connection with 23 Prozac? 24 A. That's correct, sir. Page 16 1 Q. You've written them on 2 numerous occasions? 3 A. Yes, sir. 4 Q. You have had numerous phone 5 conversations with members of the Food and Drug 6 Administration? 7 A. Yes. 8 Q. You have had numerous in 9 person meetings with members of the Food and Drug 10 Administration in connection with Prozac? 11 A. Yes. 12 Q. And these meetings began at 13 least back in 1985, didn't they? 14 A. I can't remember in '85, per 15 se, the time sequence, but I know there have been 16 meetings with the FDA about Prozac while I was 17 regulatory scientist. 18 Q. Several meetings with, in 19 person meetings with members of the Food and Drug 20 Administration and you and other Lilly employees, 21 weren't there? 22 A. That's correct, sir. 23 Q. Concerning Prozac? 24 A. That's correct, sir. Page 17 1 Q. When you were a regulatory 2 associate between 1982 and 1985, did you do any 3 work in connection with Prozac? 4 A. Not that I can recall at all, 5 sir. 6 Q. Once you became a regulatory 7 scientist dealing primarily with Prozac, did you 8 do anything specifically in connection with 9 bringing yourself up to date on what had 10 transpired in the approval process up to 1985? 11 A. My general practice, and I 12 can't remember actually doing it, but my general 13 practice on assuming any new duty would be to go 14 to our NDA files and our IND files and read the 15 correspondence, look at the documents there about 16 a particular drug, and in this case it would be 17 Prozac. 18 Q. Did you -- so you did, you do 19 recall going through the NDA files? 20 A. That's my normal process, I 21 can't remember the exact date that I went there 22 for Prozac, but my normal process would have been 23 for any new project to have done that. 24 Q. Obviously, you would have had Page 18 1 to have become familiar with the history of 2 Prozac and where it was in the approval process 3 when you began your work as a regulatory 4 scientist on Prozac in 1985, wouldn't you? 5 A. That's correct, sir. 6 Q. And that involved from you a 7 physical review of the NDA file? 8 A. The NDA file itself and the 9 IND, as well. 10 Q. Where was that document housed 11 at the time you first reviewed it? 12 A. I can't recall, sir, it was 13 within Lilly. We had several document areas that 14 evolved over the years, so I don't remember where 15 that particular one was. 16 Q. Was the NDA and the IND on 17 Prozac kept together when you first reviewed it? 18 A. It's my recollection that that 19 was the process for all of the files at that 20 time, both IND and NDA. Again, as I said 21 earlier, I can't remember exactly going and 22 sitting down at a table and looking at Prozac 23 documents, but my process was to review documents 24 when I came into a new position. And also, too, Page 19 1 I think -- our process was to house the IND and 2 NDA together so they would be physically in the 3 same area. I can't remember the exact room where 4 I went to. 5 Q. Do you recall approximately 6 how many pages of documents there were -- 7 A. No, I don't. 8 Q. -- when you first reviewed it? 9 A. It was a lot. 10 Q. Substantial number? 11 A. Yes, sir. 12 Q. Now was that IND and NDA file 13 the only information that Lilly had in connection 14 with Prozac at that time? 15 A. I really don't -- 16 Q. The only written information? 17 A. That was my assumption, yes, 18 that's why I went to review them. 19 Q. Was it your assumption in 20 1985, when you first reviewed the NDA and the IND 21 file on Prozac, that all the documents that Eli 22 Lilly and Company had were contained within the 23 IND and NDA? 24 A. Any communications with FDA, Page 20 1 yes. 2 Q. I'm not talking about just 3 communications with the FDA, I'm talking about 4 information with respect to the drug Prozac, 5 Fluoxetine Hydrochloride? 6 A. Information about the drug 7 itself, yes. 8 Q. Was there separate information 9 about the drug that wasn't contained within the 10 IND/NDA file? 11 A. I really don't know, I mean, 12 I'm trying to be as inclusive as I possibly can. 13 I'm sure that somewhere within Lilly, somebody 14 may have written about Prozac in some memo or 15 something that wasn't in the exact NDA file. Any 16 information about the drug itself, scientific or 17 medical or manufacturing and control, or any 18 records of our contact with FDA, either on the 19 IND or the NDA would be there. So I'm trying to 20 be as truthful as I can. I can't say that 21 everytime the word Prozac was written by somebody 22 within Eli Lilly that that word then wound up in 23 those files. 24 Q. Well, let's say -- and I don't Page 21 1 know that this is the case, I'm just trying to 2 give you a hypothetical example. 3 A. Sure. 4 Q. Let's say that there was a 5 document, a Lilly in-house document that was 6 giving, let's s]ay a medical monitor in 7 connection with the clinical trials, instructions 8 in connection with securing clinical 9 investigators on Prozac? 10 A. Uh-huh. 11 Q. Would that type of internal 12 memo be something that would be in the IND/NDA 13 file or would that be something that wouldn't 14 have to be filed with the Food and Drug 15 Administration? 16 A. As you described it there, I 17 don't think that would be in the file. 18 Q. All right. That's the 19 question that I'm having is, what was the 20 delineation at Lilly -- at the time you started 21 work on Prozac, what was the delineation 22 concerning what information would be submitted to 23 the Food and Drug Administration and what 24 information would remain in-house at Lilly? Page 22 1 A. As I understand it from my 2 experience, not just with Prozac, but with other 3 drugs, anything that had to do with the clinical 4 development, the toxicological evaluation, 5 manufacturing and control, the synthesis, the 6 prephase -- or I mean the pharmacology, the 7 pharmacokinetics, the pharmacodynamics, would be 8 included in those files, in addition to our 9 correspondence and memorandum or memoranda of 10 telephone conversations and other contacts, 11 meeting notes, et cetera, with the agency. 12 That's the best cut that I can give you on what 13 are in the IND and NDA files. 14 Q. Are you saying that it was 15 your practice, while you were the regulatory 16 scientist primarily involved in Prozac, that 17 memos in-house generated at Eli Lilly between Eli 18 Lilly employees concerning meetings that were had 19 between Eli Lilly employees and FDA employees 20 would be sent to the Food and Drug 21 Administration? 22 A. No. They would be in our 23 files, our IND or NDA files. They would not be 24 submitted as an official file to FDA. In other Page 23 1 words, they're not part of an IND or NDA. 2 Q. Then maybe we need to define 3 and we may have, please forgive me if we defined 4 this before, but I don't recall what it was. 5 Let's define what an IND is and what an NDA is. 6 A. Okay. Starting with IND? 7 Q. Yes. 8 A. An IND is a -- essentially an 9 investigational license application, although 10 that terminology is not used in the regulations. 11 It comes under 21 Code of Federal Regulations, 12 Part 312, and essentially in the United States 13 before you can investigate a new drug, you have 14 to submit preclinical toxicology, manufacturing 15 and control, all of the development information 16 about that drug, along with an investigational 17 plan and protocol to the Food and Drug 18 Administration for their review before you can 19 first introduce that product into a human being. 20 So all of that information is contained in an 21 IND, as well as all correspondence and all 22 contact with FDA would be included in our IND 23 file. So an IND submitted to the FDA contains 24 all of that technical information that I outlined Page 24 1 at first. And then we also keep within our IND 2 and NDA files copies of correspondence, telephone 3 conversations, meetings, et cetera, with the FDA, 4 but we don't submit those to the FDA. 5 Q. Why? 6 A. Because FDA first off has the 7 information because they keep memoranda and 8 telephone conversations and meetings themselves. 9 Also, two, there is really no obligation under 10 the regulation that we submit our memoranda and 11 telephone conversations and meetings, et cetera, 12 with them. If you look at Part 312, it's very 13 specific about what it wants. But understand -- 14 in answer to your question then, the IND that is 15 submitted to the FDA contains that technical 16 information, but we also here use the terminology 17 "our IND file" to include that plus the 18 correspondence, the memoranda of telephone 19 conversations, meetings, et cetera. 20 Q. That's the distinction I'm 21 trying to draw. 22 A. I understand, it's confusing. 23 Q. What is an IND file, and then 24 you've used IND files in connection with federal Page 25 1 regulations and then you've also used the term 2 "our IND file," which I want to make clear that 3 there are certain, if I understand it, there are 4 certain documents that federal regulations 5 require that you submit to the Food and Drug 6 Administration that become a part of the FDA's 7 IND file. 8 A. That's correct. Maybe I can 9 help things if I say that what you've just 10 described, I will, for the remainder of our 11 conversation, talk about as an IND application. 12 Q. Okay. 13 A. All right. And then that's a 14 sub-part of our IND file because our IND file 15 contains not only that application and all the 16 technical information, but also our 17 correspondence, memoranda of meetings, et cetera, 18 with the agency. Is that fair? 19 Q. Yes. Now does the IND 20 application or your IND file contain any 21 information concerning studies of Prozac in 22 connection with human beings? 23 A. Yes. 24 Q. All right. What information Page 26 1 will the IND application in your INDA file have 2 in connection with human studies? 3 A. It would be the reports of 4 those studies that we conducted under the IND 5 application. 6 Q. All right, maybe I 7 misunderstood you. I thought the IND application 8 had to do only with those studies done prior to 9 Fluoxetine being given to human beings, is that 10 not correct? 11 A. That's the initial 12 application, but as you proposed each subsequent 13 trial and study, the protocol and related 14 information pertaining to those proposed studies 15 are also submitted to the IND application as 16 amendments or as supplements or as subsequent 17 submissions. 18 Q. What is an NDA then? 19 A. NDA, then, is a compilation of 20 all of the information that you developed under 21 the IND, plus additional manufacturing and 22 control, chemical development, toxicology, 23 preclinical and other development data that came 24 to light or was developed during the time of the Page 27 1 IND. So, in other words, it's essentially the 2 information that would originally have been in 3 the IND application, plus all the additional 4 similar information that you have developed 5 during the time of that IND study or studies. 6 Q. Why is there a distinction 7 between the two? It sounds to me like they're 8 both going to include the same things. 9 A. Right, and I left out a part 10 of my answer, and I apologize for that. As I 11 said, the investigational new drug, the IND, is 12 essentially an application for investigational 13 license. The NDA, the new drug application, 14 which is under Part 21 CFR 314 of the Code of 15 Federal Regulations, is essentially a marketing 16 license application. In other words, you 17 investigate under an IND, you study and develop a 18 drug under an IND. You gain approval to market 19 and sell the drug once you submit an NDA and it's 20 approved. 21 Q. Do you recall when the IND 22 with respect to Prozac was initially submitted? 23 A. No, Mister Smith, I don't. 24 Q. Can you give me the year? Page 28 1 A. I don't even know that, sir, 2 I'm sorry. 3 Q. All right. I'm talking about 4 Prozac. 5 A. Yes, I understand. 6 Q. I don't know if I ever got 7 Prozac out in that part of the question. 8 A. I figured that's what we were 9 talking about. 10 Q. How about NDA, when was the 11 NDA -- 12 A. The NDA, I believe, was filed 13 in the early '80s. And again, it was filed prior 14 to my assuming the regulatory scientist duties in 15 1985, I remember it was the early '80s though. 16 Q. Would there be anything in the 17 NDA that wouldn't be submitted in the IND? 18 A. Yes, the results of the large 19 multi center trials, for example. 20 Q. Why wouldn't they be submitted 21 as part of the IND? 22 A. Because when you got them 23 completed you would have the basis of your NDA 24 and then you would submit the NDA. These are Page 29 1 Phase 3 trials I'm talking about. 2 Q. I probably remember the number 3 by heart. The data that we have or 4 correspondence that we have refers to the Prozac 5 NDA as bearing number 18 dash 936. 6 A. You know, Mister Smith, 7 actually I don't remember that number by heart, 8 but if you have it there, I am willing to accept 9 that. 10 Q. All right. Do you recall what 11 the IND number was? 12 A. No, sir, I don't, I'm sorry. 13 Q. Would it bear a different IND 14 number than the NDA number? 15 A. Yes. Usually I think the 16 number that you just read me for the NDA probably 17 had a dash between the first two digits and the 18 last three. 19 Q. Uh-huh. 20 A. And I think that an IND number 21 typically has been either four or five 22 consecutive digits separated only by a comma on 23 occasion. 24 Q. To make the record clear, the Page 30 1 NDA number on Prozac is NDA 18 dash 936. 2 A. Okay. 3 MR. SMITH: Do we have any problem, 4 Counsel, with that number as being the NDA number 5 in connection with Prozac? 6 MR. MYERS: I don't think we do. 7 Right now, we don't. 8 MR. SMITH: Right now, we don't? 9 MR. MYERS: Well, there may be some 10 additional NDAs or some supplements that may have 11 different numbers, but I think we all know what 12 we are talking about right now. 13 MS. ZETTLER: The NDA for depression. 14 MR. MYERS: Right. 15 MR. SMITH: This would be the NDA for 16 depression? 17 MR. MYERS: Right, yes. 18 MR. SMITH: The 18 dash 936, correct? 19 MR. MYERS: Right, absolutely. 20 Q. (BY MR. SMITH) All right. 21 Would the NDA have all the information that Lilly 22 had on Prozac, comma, Fluoxetine Hydrochloride, 23 comma, that Lilly had in connection with Prozac? 24 MR. MYERS: Before he answers, let me Page 31 1 object to the form and the term "all the 2 information" as being awfully broad. But if you 3 know, Doctor Talbott, tell him. 4 A. Well, again, like I said a 5 little bit earlier, I can't really comment that 6 every time that somebody wrote Prozac or 7 Fluoxetine within the corporation, that memo 8 found it's way to the NDA. But I would answer 9 your question by saying all of the information 10 obtained by studies conducted under the IND and 11 related internal studies on toxicology, 12 development, manufacturing and control, et 13 cetera, would be in the NDA. 14 Q. Well, if there was a -- if 15 there were notes made by Lilly employees 16 concerning meetings with Food and Drug 17 Administration employees, would those be 18 submitted to the Food and Drug Administration as 19 part of the NDA? 20 A. No, they would not. 21 Q. For the same reasons that you 22 gave me earlier concerning the IND? 23 A. That's correct, sir. 24 Q. That is that internal Page 32 1 memoranda generated by Lilly are not required to 2 be submitted to the Food and Drug Administration? 3 A. Yes, sir. 4 Q. Is it the -- based on your 5 experience with the -- well, being employed with 6 the Food and Drug Administration and based on 7 your experience being in regulatory affairs with 8 Eli Lilly and Company, is it the intent of the 9 federal regulations, as far as you know, that the 10 requirements to submit material to the Food and 11 Drug Administration is basically that a 12 pharmaceutical firm should submit to the Food and 13 Drug Administration as much information as they 14 know concerning the particular product, drug 15 being investigated? 16 A. The regulations are very 17 explicit about the kind of information that is to 18 be submitted, and it's always been our policy, 19 and in my observation our practice, to follow 20 those to the letter. So information that fits 21 either the IND or the NDA requirements, I agree 22 with you, yes, that's exactly why we submit them. 23 Q. Is it Lilly's policy to let 24 the Food and Drug Administration have as much Page 33 1 information concerning the properties of Prozac 2 that Lilly has? 3 A. I think that's a fair 4 statement, yes. 5 Q. Whether the federal 6 regulations specifically, actually, require a 7 piece of information to be submitted from Lilly 8 to the FDA, is it Lilly's policy to let the Food 9 and Drug Administration have the benefit of as 10 much knowledge concerning Prozac as Lilly does? 11 A. Again, I know I'm being 12 tedious and please bear with me, but when you say 13 information, that to me means, again, you know, 14 if there is one memorandum that has the term 15 Fluoxetine in it, theoretically that's 16 information about Fluoxetine and I can't sit here 17 this morning and say that everytime the word 18 Fluoxetine is used in a memoranda, we submitted 19 that piece of information to the agency. But 20 technical information as described under the IND 21 and the NDA regs, yes. 22 Q. Let's be more specific here. 23 How about information concerning side effects of 24 Prozac, would it be Lilly's policy to submit all Page 34 1 information that Lilly had concerning side 2 effects or potential side effects of Prozac to 3 the Food and Drug Administration? 4 A. Yes, sir. 5 Q. Would it be Lilly's policy to 6 submit to the Food and Drug Administration all 7 information concerning adverse experiences 8 sustained by patients or individuals taking 9 Prozac to the Food and Drug Administration? 10 A. Yes, sir. 11 Q. Is the information that is 12 learned about Prozac in other countries submitted 13 to our United States regulatory body, the U.S. 14 Food and Drug Administration by Lilly? 15 A. Yes, sir. 16 Q. All information? 17 A. To my understanding, yes, sir. 18 Q. Is information concerning 19 memoranda between Lilly employees in a foreign 20 country and Lilly employees in Indianapolis 21 concerning specific reporting requirements and 22 characterizations of adverse reactions submitted 23 by Lilly to the United States Food and Drug 24 Administration? Page 35 1 A. I lost the train on that, 2 would you mind reading it back to me? 3 (THE COURT REPORTER READ BACK THE 4 REQUESTED TESTIMONY.) 5 MR. MYERS: Before he answers, let me 6 object to the form because I don't know that the 7 question delineates between information and your 8 example which is the actual memoranda, I don't 9 know if the question is clear about that. 10 A. If you can tell me which one 11 you meant then I think I can answer. 12 Q. Were there any memoranda? 13 A. The memoranda themselves 14 perhaps would not be, but the information 15 contained in them would probably be submitted in 16 a summary fashion or in an official submission. 17 The memoranda -- in answer to your question now 18 as I understand it, the memoranda themselves 19 would not. 20 Q. Why? 21 A. Again I think this falls under 22 the discussion we've had earlier that internal 23 correspondence, memoranda between Lilly 24 individuals, even memoranda about Lilly meetings Page 36 1 with FDA people and telephone conversations with 2 FDA people, we've not submitted as part of the 3 application. 4 Q. Well, what if there was a 5 discussion within employees of Eli Lilly and 6 Company, concerning how to characterize a 7 particular adverse event and how to report a 8 particular adverse event, wouldn't that be 9 something that should be submitted to the Food 10 and Drug Administration? 11 A. The adverse events, certainly. 12 Q. Well, not just a 1639 or an 13 international report of an adverse event, but if 14 there were discussions concerning how 15 specifically to characterize that adverse event 16 with respect to reporting purposes, shouldn't 17 that be submitted to the Food and Drug 18 Administration? 19 A. You mean the dialogue of our 20 conversation about how to classify a particular 21 adverse event? 22 Q. Yes. 23 A. I don't know that the agency 24 would want that or could even use that. I think Page 37 1 what they would be concerned with is our 2 characterization of the event, if we used the 3 Costart terminology, and then if we reported it 4 within the regulatory mandated time frames, ten 5 days for IND's, fifteen days for serious 6 unexpected spontaneous events, et cetera. 7 Q. You are now director of 8 worldwide regulatory affairs? 9 A. Yes, sir. 10 Q. And that requires you to deal 11 on a daily basis with your affiliates throughout 12 the world? 13 A. My regulatory affiliates, 14 that's correct, sir. 15 Q. You know who Hans Weber is? 16 A. I know Hans very well, yes, 17 sir. 18 Q. Hans is who? 19 A. Hans is presently the medical 20 director of our German affiliate in Bad Homburg, 21 is their location. 22 Q. Do you know Claude Bouchy? 23 A. I've talked with Claude, I 24 don't believe I've ever met him though. I Page 38 1 believe he is in the general management side in 2 Europe, I don't know what his current title is 3 though, sir. 4 Q. But Hans Weber and Claude 5 Bouchy are both Lilly employees in Europe? 6 A. Yes, sir, they are. 7 Q. Specifically in France? 8 A. Well, no, I think Hans is in 9 Germany, and I don't know where Claude is. If I 10 were to go on his name, I'd say it's probably one 11 of the French speaking countries, Belgium or 12 Switzerland or France. But I really don't know, 13 Mister Smith, I can't tell you. It's in Europe 14 somewhere. 15 Q. In November of 1990, Mister 16 Bouchy or Doctor Bouchy -- is it Mister or 17 Doctor? Doctor Bouchy was in France, wasn't he? 18 A. I can't help you, I would see 19 no reason why you would tell me incorrectly. 20 Q. Do you know if Claude Bouchy 21 is still an employee with Lilly? 22 A. I believe he is, yes. 23 Q. And you know Hans Weber is? 24 A. Hans I know very well, sure. Page 39 1 Was your question whether Hans is still an 2 employee with Eli Lilly? 3 Q. Yes. 4 A. He is too, I also know him and 5 he is an employee. 6 (PLAINTIFFS' EXHIBIT 1 WAS 7 MARKED FOR IDENTIFICATION AND 8 RECEIVED IN EVIDENCE.) 9 Q. Have you had the opportunity 10 to review that exhibit? 11 A. Yes, sir, I have. 12 Q. Do you recall ever seeing 13 Exhibit Number 1, Doctor Talbott? 14 A. I have reviewed this document 15 and a group of documents that was given to me in 16 conjunction with my deposition, about four boxes. 17 Q. All right. 18 A. And at the time that I saw it, 19 I didn't know why it had gotten in there 20 basically because my name wasn't on it. But it 21 was there, so. 22 Q. When you reviewed this 23 document, did you have any recollection of seeing 24 this document? Page 40 1 A. No, I didn't, at the time, 2 Mister Smith. I think that's what kind of 3 prompted my question of even why it was in my 4 box, the boxes. 5 Q. In November of 1990, the date 6 of this memo, you were the director of regulatory 7 affairs? 8 A. Medical regulatory affairs, 9 that's correct, sir. 10 Q. And you were the individual 11 responsible for seeing that Eli Lilly and Company 12 complied with all federal regulations in 13 connection with Prozac? 14 A. Prozac, that's correct, sir. 15 Q. This memorandum states -- 16 well, this is a memorandum from Claude Bouchy to 17 Leigh Thompson, is it not? 18 A. Yes, it's kind of confusing 19 because there is a little -- two or three blocks 20 of typing up at the top and then Leigh's name on 21 the bottom, but it's -- it looks like maybe it 22 was forwarded, in fact it does say it was a 23 forwarded message. But, yes, in answer to your 24 question, that's right. It's from Mister Bouchy Page 41 1 to Doctor Thompson with five CC's on there, dated 2 November 14th, 1990. 3 Q. Let's talk about the 4 individuals to whom this memorandum was directed, 5 it was directed to Leigh Thompson, correct? 6 A. Originally to Leigh, he was 7 the primary addressee, yes, sir. 8 Q. Leigh Thompson is now the 9 chief regulatory scientist, a corporate officer 10 with Eli Lilly and Company, is he not? 11 A. No, sir, he is not. 12 Q. He is the chief scientific 13 officer? 14 A. That's correct, sir. 15 Q. A corporate officer with Eli 16 Lilly and Company? 17 A. That's correct, sir. 18 Q. And at the time this memo was 19 dictated in November of 1990, what was his job 20 title? 21 A. Give me a second to -- I 22 believe at the time, Mister Smith, he was 23 vice-president of Lilly Research Laboratories. 24 Q. He was a corporate officer Page 42 1 then in November of 1990? 2 A. I don't know -- I don't know 3 if he was a corporate officer or not, sir. You 4 might have to help me with that because I'm 5 really not sure what corporate officer means. 6 Q. Well, you said he was 7 vice-president. 8 A. Yes. 9 Q. That generally denotes 10 corporate officer. 11 MR. MYERS: Let me object to the form. 12 If you know if he was, Doctor Talbott, tell him, 13 if you don't know, tell him that. 14 A. I think I said I didn't know. 15 I know he was vice-president of Lilly research 16 laboratories, that I do know. 17 Q. And you know now he is the 18 chief scientific officer of Eli Lilly and 19 Company? 20 A. That's correct, sir. 21 Q. And you know he is corporate 22 officer now, don't you? 23 A. Because his name appears in 24 the annual report. Page 43 1 Q. He is a twelfth floor, his 2 office is on the twelfth floor? 3 A. His office is on the twelfth 4 floor in Building 74. 5 Q. And that's where the highest 6 ranking members of Eli Lilly and Company office, 7 isn't it? 8 A. Most of them are there, yes. 9 Q. That's where the president of 10 Eli Lilly and Company's office is, isn't it? 11 A. I have not had an occasion to 12 visit Mister Tobias, but yes, his offices are up 13 there. 14 Q. And that's where the chief 15 executive officer's office is, is it not? 16 A. I believe Mister Tobias is 17 also CEO. 18 Q. So the memo is to, at least, 19 to Mister Leigh Thompson, who was at that point 20 at least a vice-president of Lilly Research Labs? 21 A. That's correct, sir. 22 Q. And the individuals copied on 23 this memo are Mister Gerhard Mayr, M-A-Y-R? 24 A. May I correct your Page 44 1 punctuation? 2 Q. Certainly 3 A. Gerhard Mayr. 4 Q. What is his job duties? 5 A. He is -- I believe he was a 6 vice-president and still is of general operations 7 in Europe. I don't know that that's the official 8 title, but that's an operational title. 9 Q. So he was a foreign Lilly 10 corporate officer? 11 A. If you would say foreign Lilly 12 executive, I could answer, but corporate officers 13 cause me some trouble because I don't know if 14 that's something specific or generic. 15 Q. Let's use the term then 16 executive. He's a European Lilly executive, is 17 that okay? 18 A. That's helpful, Mister Smith, 19 yes. 20 Q. Was he the chief executive 21 responsible for the European operations? 22 A. I really don't know at that 23 time, because I don't recall -- the next name on 24 there, and I'm sure you will get to it, Mister Page 45 1 Taurel, I'm not sure what Mister Taurel's 2 position was at that time, he could have been the 3 chief for Europe. If he were, then Mister Mayr 4 would have been just right below him. Both of 5 them executives, though. 6 Q. Did Mister Gerhard Mayr office 7 in Europe in November, 1990? 8 A. Yes, Gerhard's office was in 9 Europe. 10 Q. Gerhard. And is it Doctor or 11 Mister Taurel? 12 A. It's Mister. 13 Q. Mister Taurel. And you say he 14 would have been senior? 15 A. Could have been -- I'm sorry 16 to interrupt, he could have been. 17 Q. Where did he office? 18 A. I believe at that time his 19 offices were here in Indianapolis. 20 Q. Was he Twelfth Floor? 21 A. I really don't know. I really 22 don't know, I'm sorry. 23 Q. And Hans Weber was a medical 24 doctor in Europe? Page 46 1 A. Give me a second to 2 reconstruct. I believe that Hans was the medical 3 director then at Bad Homburg, he is a physician 4 though. 5 Q. And Allan Weinstein? 6 A. You want his title? 7 Q. Yes. 8 A. He was vice-president of Lilly 9 Research Laboratories. 10 Q. He was a corporate executive? 11 A. Yes. 12 Q. Robert Zerbe? 13 A. Doctor Zerbe, I believe, was 14 an executive director then of Lilly Research 15 Laboratories. 16 Q. The date is November 14th, 17 1990, the time is 5:58, correct? 18 A. Well, actually there are two 19 times on there, Mister Smith. It looks -- it's 20 very strange, one, there is one November 14, 1990 21 date and time line that's 06:47, then there's the 22 addressees and then there's another date and time 23 line that says November 14th, 1990, 05:58, then 24 the text of the note. So it was 5:00 or 6:00 Page 47 1 o'clock in the morning. 2 Q. It would be A.M. then? 3 A. Yes, sir, it's on military 4 time, twenty-four hundred hour clock. 5 Q. The memo is regarding Adverse 6 Events Reporting-Suicide Fluoxetine, is it not? 7 A. Actually the referral line is, 8 Adverse Event Reporting, dash, Suicide 9 Fluoxetine. 10 Q. Well, the memo is concerning 11 reporting suicide with Fluoxetines as an adverse 12 event, isn't it, Doctor Talbott? 13 A. That's what the title says, 14 yes, sir. 15 Q. That's what the text of it is 16 too, you've read it. 17 A. Right. 18 Q. The memo says, "Thank you very 19 much for your prompt answer and your detailed 20 explanations." Who is this, Hans? 21 MR. MYERS: Hans. 22 A. I believe it's referring again 23 to Doctor Webber. 24 Q. Hans and I discussed the issue Page 48 1 in depth. It goes on to say, and this is Doctor 2 Bouchy talking to Doctor Leigh Thompson, isn't 3 it? 4 A. Yes, sir -- well, not talking 5 to him, he was writing to him. 6 Q. Writing to him and copying in 7 these other corporate executives, correct? 8 A. Mister Mayr, Mister Taurel, 9 Doctor Weber, Doctor Weinstein, Doctor Zerbe, 10 yes, sir. 11 Q. It says, "Our point is the 12 following:the physician has reported a suicide 13 attempt. Do we have a right to change it to some 14 terminology which we may consider to be more 15 specific, e.g. overdose, but which is not free 16 from ambiguity and could be regarded as 17 inaccurate or misleading? The term overdose is 18 not free from ambiguity because there are clearly 19 forms of overdose which are not related to 20 suicide attempts, for instance wrong dose 21 prescribed or dispensed, error on the part of the 22 patient, et cetera. In fact, and perhaps more 23 importantly, the dictionaries we have looked at," 24 paren, "medical dictionaries and non-medical," Page 49 1 close paren, "fail to associate," paren, "not to 2 mention equal," close paren, the concept of 3 overdose with suicide attempt. In addition, it 4 can be argued that the event overdose is 5 inaccurate" or an overdose of barbiturates and 6 tryciclics -- 7 MR. MYERS: You missed a line, Paul. 8 You want -- you skipped a whole line. 9 Q. "Is inaccurate or misleading 10 because in this case the patient attempted 11 suicide by taking an overdose of barbiturates and 12 tryciclics and not, I repeat not, of Fluoxetine. 13 Finally, on a very simple and non-scientific 14 basis, I personally wonder we are really helping 15 the credibility of an excellent ADE system by 16 calling overdose what a physician reports as 17 suicide attempt, and by calling depression what a 18 physician is reporting as suicide ideation. We 19 fully realize that there is no code in our DEN 20 system for suicide ideation, but it could be 21 argued by people who have little sympathy for the 22 company or by regulatory authorities that it is 23 not a responsible way to deal with an issue which 24 is getting so much attention in the scientific Page 50 1 and in the general press. It could also be 2 argued that the term depression is not specific 3 in this case. Of course, at the end of the day, 4 we will do what we are told to do, but Hans and I 5 felt that we need to bring these points to your 6 attention." Have I read that memo correctly? 7 A. Yes, a word or two, but I 8 think you read the vast majority of it correctly. 9 Q. All right. Now, your 10 testimony is to be clear that when you reviewed a 11 box of documents several months ago in 12 preparation for your deposition in these cases, 13 this was the first time you recalled seeing this 14 document? 15 A. Yes. The only clarification I 16 would make is that I have also reviewed those 17 documents within the last month or so. You said 18 several months, I want to be absolutely accurate. 19 That is correct, sir. 20 Q. Did you review this document 21 just a few weeks ago? 22 A. As I said earlier, this one 23 struck me because I wondered why it was in my box 24 because it didn't have my name on it. Page 51 1 Q. This memorandum does mention 2 an adverse reaction with Prozac, doesn't it? 3 A. Adverse event reporting, yes, 4 sir. 5 Q. And as a matter of fact, the 6 title of it is adverse event reporting, isn't it? 7 A. That's correct, sir. 8 Q. And specifically adverse event 9 reporting in connection with Fluoxetine suicides, 10 isn't it? 11 A. The title again is Adverse 12 Event Reporting-Suicide Fluoxetine. 13 Q. So the answer to my question 14 would be yes? 15 A. Well, no, you read a different 16 title than what I just read. 17 Q. Well, but the subject is 18 concerning the reporting of the adverse event of 19 suicides by people using Prozac? 20 A. Right, event terminology, 21 correct, sir. 22 Q. And there's a discussion here 23 between Doctor -- or there is a discussion here 24 between Doctor Bouchy and Doctor Thompson Page 52 1 concerning the proper way to characterize. 2 A. Well, a discussion to me, not 3 to bandy words, but a discussion to me involves 4 two way. 5 Q. There is a communication. 6 A. There is a note from Mister 7 Bouchy to Leigh and others, so that's my 8 response. It's not a discussion unless something 9 back from Leigh that says here's what I say, then 10 it's a discussion. 11 Q. All right. Well, it talks 12 about an excellent ADE system, doesn't it? 13 A. Yes, sir. 14 Q. And it talks about terminology 15 to be used in connection with adverse events, 16 right? 17 A. That's correct, sir. 18 Q. And it talks about serious 19 adverse events, doesn't it. 20 A. I believe that term was in 21 there, yes, sir. 22 Q. And suicide is a serious 23 adverse event, isn't it? 24 A. Yes, sir. Page 53 1 Q. In November of 1990, there was 2 a general sense of concern within Eli Lilly and 3 Company, was there not, Doctor Talbott, 4 concerning a possible relationship with suicide 5 and suicidal ideation and the use of Prozac? 6 MR. MYERS: Before he answers, let me 7 object to the form to the extent of the general 8 concern you have cited, if your question assumes 9 it rises out of this memo then I would object to 10 the form because I think it mischaracterises the 11 memo. But if you know, Doctor Talbott, tell 12 Mister Smith. 13 A. I really can't speak to what a 14 general concern was, I know there was some 15 questions being raised. 16 Q. And you as the director of 17 medical regulatory affairs having primary 18 responsibility in dealing with the Food and Drug 19 Administration knew that there was a concern, 20 didn't you? 21 A. I knew that there was concern, 22 I think that was my testimony. There was some 23 questions about suicide and Fluoxetine. 24 Q. You had some concern about Page 54 1 that at the time, didn't you, Doctor Talbott? 2 A. About suicide and Fluoxetine, 3 I think that's my response. 4 Q. And you had concerns about 5 that? 6 MR. MYERS: He's answered that. I 7 object, he's asked and answered. Tell him one 8 more time. 9 A. There were questions about 10 suicide and Fluoxetine. 11 Q. And you were discussing that 12 with the Food and Drug Administration, weren't 13 you? 14 MR. MYERS: At what point in time? 15 Q. In November of 1990, or 16 anytime in 1990? 17 A. I can't say anytime in 1990, 18 but during this timeframe, yes. 19 Q. Certainly by November of 1990, 20 you had had discussions with members of the Food 21 and Drug Administration concerning the issue of 22 Prozac and suicide, hadn't you? 23 A. Yes. 24 MR. MYERS: Hold on. When you say Page 55 1 you, do you mean him or others at Lilly? 2 Q. You. Number one, you had, 3 hadn't you? 4 A. Very honestly, I don't know if 5 at that time I had. If your question to me is, 6 have you, Max Talbott, on and of that date had a 7 discussion with FDA that you recall or have some 8 evidence of, I can't say yes or no to that. 9 Q. You had at least been present 10 at meetings and had been privy to telephone 11 conversation between Lilly employees and FDA 12 employees by November of 1990 -- 13 A. By this time. 14 Q. -- concerning the issue of 15 whether or not Prozac caused people to commit 16 suicide? 17 A. That's correct. 18 Q. And by November 1990, the Food 19 and Drug Administration had made it known to you 20 as the director of medical regulatory affairs, 21 that the Food and Drug Administration was 22 interested in what data Lilly had concerning the 23 issue of Prozac and suicide. 24 A. Again, Mister Smith, if you Page 56 1 can show me a document or a certain 2 correspondence that would help me recollect that, 3 I would be glad to respond to it. I can't here, 4 well, three and a half years later say somebody 5 called me on, you know, November 13th and this 6 person was Doctor Jones and he asked me for such 7 and such. So I want to be as truthful as I can, 8 I cannot say yes specifically to that. If you 9 can show me something I will be glad to respond 10 to it. 11 Q. I'll get to that in a minute. 12 I think we will be able to show you documents 13 that will reflect that the Food and Drug 14 Administration employees were by November 1990, 15 interested in what data Lilly had concerning 16 suicide and Prozac. 17 A. Fair enough. 18 Q. With respect to reporting of 19 adverse events. 20 A. Fair enough. 21 Q. But, to continue with this, at 22 least, this memo, Exhibit 1, you were aware that 23 there was an issue that had been discussed with 24 the Food and Drug Administration at least by Page 57 1 November of 1990? 2 A. By people within Lilly, maybe 3 not by me specifically. That's correct, sir. 4 Q. Yes. Do you know why, at that 5 time, that there were reports of suicide attempts 6 being given to Lilly by physicians and then that 7 report was being changed to depression -- or that 8 event was being reported as depression or 9 overdose and not suicide attempt? 10 A. The best that I can understand 11 is that Mister Bouchy's note here is about the 12 Costart dictionary, and the Costart dictionary is 13 an adverse event terminology dictionary that is 14 developed and maintained -- was developed and is 15 maintained by the U.S. Food and Drug 16 Administration. And within that dictionary then, 17 they have very rigorously set terms and subterms 18 which you have to map spontaneous event terms, 19 which I think Mister Bouchy must be talking about 20 here, to -- for reporting to the agency. What 21 the agency allows manufacturers to do and what we 22 have done is to include in the free text portion 23 of the adverse event report, any commentary by 24 the physician or the reporter for any additional Page 58 1 narrative commentary that we have included, so 2 that the Costart event term itself is not the 3 only means of reporting the adverse event. 4 Q. But, don't you agree that 5 suicide attempt is more specific than depression 6 or overdose? 7 MR. MYERS: Well, let me object to the 8 form, only to the extent it might call for him to 9 form some kind of clinical judgment about the use 10 of those terms. 11 Q. No. My question to you is 12 directed as the director of medical regulatory 13 affairs at Eli Lilly and Company and that 14 individual primarily responsible at Lilly with 15 reporting adverse events to the Food and Drug 16 Administration. 17 MR. MYERS: Notwithstanding that 18 caveat, I have the same objection. But if you 19 know, tell him. 20 A. I don't agree with that, 21 Mister Smith, because I think the Costart term, 22 which is the dictionary itself which the agency 23 has maintained for years, is very specific and 24 that coupled with the narrative information in Page 59 1 the adverse event reports is a complete picture 2 of what happened. 3 Q. Well, isn't what Doctor Bouchy 4 is saying is is that a complete picture is not 5 what's being presented? 6 A. No. 7 MR. MYERS: Hold on, let me object to 8 the form. The question calls for him to 9 speculate as to what Doctor Bouchy meant in 10 November of '90. 11 Q. I'm not asking you for a 12 speculation, I'm asking you for your review as 13 the director of medical regulatory affairs 14 responsible at Lilly for accounting to the Food 15 and Drug Administration for Lilly's conduct in 16 connection with the marketing of Prozac to 17 citizens of the United States of America. 18 MR. MYERS: Same objection as to the 19 form, notwithstanding your caveat. 20 A. I lost track of the question, 21 would it be okay to have it read back? 22 Q. Let me just repeat it, but 23 keep in mind that caveat. Don't you think that 24 Doctor Bouchy here is concerned about whether or Page 60 1 not it is misleading to report a suicide attempt 2 as overdose or depression? 3 MR. MYERS: Same objection as to form, 4 it would be speculative. If you know what he 5 intended or meant, tell him. 6 A. Again, I've never met Claude, 7 I talked to him several times, not about this, so 8 I can't speculate, I'm sorry. 9 Q. Do you have any reason to 10 question Doctor Bouchy's judgment on anything? 11 A. No. 12 Q. Do you have any reason to 13 think that Doctor Bouchy is wrong in what he 14 states here, what is written down? 15 A. Factually wrong? 16 Q. Yes. 17 A. I'm not sure he understands 18 Costart, that's my take on it. 19 Q. Okay. Other than maybe an 20 inaccurate or incomplete understanding of 21 Costart, do you see any other errors that Doctor 22 Bouchy has made in the text of this memo? 23 A. No, but that's a pretty broad 24 one because that's kind of the gist of the whole Page 61 1 thing, the kind of terminology. But no, in 2 answer to your question, Mister Smith, no. 3 Q. In this memo, Doctor Bouchy 4 here says, it could be argued by people who have 5 had little sympathy for the company or by 6 regulatory authorities that it is not a 7 responsible way to deal with an issue which is 8 getting so much attention in the scientific and 9 in the general press. Doesn't it? 10 A. Yes, that's written here, you 11 read that correctly, sir. 12 Q. And did you pass this memo on 13 to the Food and Drug Administration? 14 A. Did I? 15 Q. Yes. 16 A. Not that I am aware of. 17 Q. Do you know whether or not the 18 Food and Drug Administration has ever received 19 this document marked Exhibit 1? 20 A. No, sir, I don't, I'm sorry. 21 Q. Would you be the ultimate 22 person or would you have been the ultimate person 23 at Eli Lilly and Company in November 1990 to 24 forward this document to the FDA if it was Page 62 1 forwarded to the FDA? 2 A. Yes, sir, I would have been. 3 Q. If you had done that, would 4 you have done it by means of a transmittal 5 letter? 6 A. You mean -- can you explain 7 what transmittal letter means? 8 Q. A transmittal letter, some 9 piece of correspondence where you identify 10 Fluoxetine Hydrochloride, Prozac, NDA number 18 11 dash 936, saying -- directed -- addressed to 12 Rockville, Maryland, Food and Drug 13 Administration, and asking them to put this in 14 their NDA file or IND file? 15 A. Right now, I thank you for 16 explaining that. I would, had we submitted 17 anything to either the IND or NDA application, 18 per our previous conversation about the 19 distinctions between application and files, et 20 cetera, I would have been the person to have done 21 that transmittal letter and to have signed it and 22 to have sent it, yes, sir. 23 Q. Is this document, Exhibit 1, a 24 document that you, as the director of medical Page 63 1 regulatory affairs, responsible for Prozac, would 2 have forwarded on to the Food and Drug 3 Administration? 4 A. If there had been an adverse 5 event reported here, we would have put that into 6 a form and would have submitted it, but this 7 note, this Exhibit 1? 8 Q. Yes. 9 A. Myself? No, I wouldn't have. 10 Q. If someone had come to you, I 11 guess -- let's back up a little bit. You don't 12 know for sure that this wasn't submitted to the 13 Food and Drug Administration? 14 A. No, I don't, but the file 15 would speak to that -- I mean the application, 16 the NDA application would speak to that. 17 Q. It can be easily found if it's 18 there, or if it's not there, it's not there, 19 correct? 20 A. Yes. 21 Q. But, if somebody were to come 22 to you with this document and say Doctor Talbott, 23 since this has to do with regulatory authorities, 24 it has to do with adverse event reporting and Page 64 1 since this has to do with a serious adverse 2 event, is this something that we should submit to 3 the Food and Drug Administration. 4 A. Somebody might do that, you 5 would say? 6 Q. If somebody had come to you 7 and asked you, should this be sent to the Food 8 and Drug Administration -- 9 A. Right. 10 Q. -- what would your reply have 11 been? 12 A. I would have said, unless it 13 contains an adverse event report which we will 14 move into a 1639 which is the regulatorally 15 mandated mechanism for reporting adverse events, 16 I would not submit this to the agency, no, sir. 17 Q. Why? 18 A. I don't think it has any 19 information in it. 20 MR. SMITH: Okay. We can take a quick 21 break. 22 (A SHORT RECESS WAS TAKEN.) 23 Q. (BY MR. SMITH) As the 24 director of medical regulatory affairs in Page 65 1 November 1990, are you saying that you condone 2 the practice mentioned by Doctor Bouchy of 3 calling overdose what a physician reports as 4 suicide attempt? 5 A. I guess the way I respond to 6 that, Mister Smith, is that I support the use of 7 the Costart FDA's adverse event terminology 8 dictionary approach to mapping adverse event 9 terms, but also including in summary form or in 10 narrative form all the information reported by an 11 adverse event report. 12 Q. Well, what is magic about 13 Costart? 14 A. I don't know how to respond to 15 that, sir. 16 Q. Do the Code of Federal 17 Regulations or does the FDA require that you use 18 Costart terms in reporting adverse events? 19 A. FDA recommends that we do, 20 strongly suggests. 21 Q. Do they require it? 22 A. You mean is it in the 23 regulations or laws? 24 Q. Yes. Page 66 1 A. No, sir. 2 Q. Don't the regulations and the 3 laws require that you give a specific and an 4 accurate description of a particular adverse 5 event? 6 A. Yes, sir. 7 Q. And they do not require that 8 you have to use Costart, do they? 9 A. No, I think I already answered 10 that. 11 Q. Do you agree or disagree with 12 Doctor -- do you agree as in your position of 13 director of medical regulatory affairs in 14 connection with Prozac at the time, that this is 15 not a responsible way to deal with this issue? 16 A. No, I totally disagree with 17 that. 18 Q. Did you ever dictate anything 19 to Doctor Bouchy concerning your disagreement in 20 this connection? 21 A. I don't recall doing that, no, 22 sir, and it wasn't in any of the documents that I 23 recently reviewed that we talked about earlier. 24 Q. Has it always been Lilly's Page 67 1 policy to report as fully as possible any 2 particular adverse event in connection with 3 Prozac? 4 A. Not only with Prozac, but with 5 all of our drugs. 6 Q. While you were the director of 7 medical regulatory affairs, did you consider the 8 Food and Drug Administration as being an 9 adversary with Lilly in connection with Prozac? 10 A. I think adversary might be a 11 little to strong. 12 Q. What term would you use then? 13 A. Federal regulatory agency, law 14 enforcement agency. 15 Q. Well, did you consider that 16 the Food and Drug Administration was supportive 17 of Lilly's position in connection with the issue 18 of Prozac and suicidality? 19 MR. MYERS: Did he consider that, that 20 was a -- 21 MR. SMITH: Yes. 22 A. Could you play that back, I'm 23 sorry. 24 Q. Did you consider that the Food Page 68 1 and Drug Administration was supportive of Lilly's 2 position in connection with whether or not Prozac 3 caused suicidal ideation and suicide? 4 MR. MYERS: At what point in time? 5 MR. SMITH: In November of 1990. 6 A. At that time, I don't know 7 that I had any opinion about where the agency was 8 at all, in 1990. 9 Q. Did your position ever change 10 at any time -- 11 A. You mean my position, sir? 12 Q. Yes, your position with 13 respect to -- 14 A. I'm sorry, I interrupted. 15 Q. -- your position with respect 16 to whether or not the FDA was supportive of 17 Lilly's position in connection with Prozac and 18 suicide attempts and suicidal ideation? 19 A. Yes, now I do. I have a 20 feeling that they -- I'm not sure that they 21 support the position, but that they feel that 22 they are not related and this is based on the 23 advisory committee meeting that took place in 24 1991, and then some reports or commentary that Page 69 1 the agency put out during that same period of 2 time. But again, in 1990, that was 1991 or 3 after, and we are talking about today versus 4 1990. I just want to be sure to keep the time 5 frame square. 6 Q. So, is it your testimony that 7 you don't have any recollection of any particular 8 support that the FDA had or didn't have in 9 connection with Lilly's position that Fluoxetine 10 didn't cause suicidality in November of 1990? 11 A. That's my testimony, yes, sir. 12 Q. Then let's look as Exhibit 13 Number 2. 14 (PLAINTIFFS' EXHIBIT 2 WAS 15 MARKED FOR IDENTIFICATION AND 16 RECEIVED IN EVIDENCE.) 17 Q. You dictated the memo, Number 18 2, didn't you? 19 A. I wrote it, I authored it, I 20 don't think I dictated it, per se. 21 Q. You wrote it, correct? 22 A. That's correct, sir. 23 Q. And that was a memorandum of a 24 meeting that was held between the Food and Drug Page 70 1 Administration and Lilly, wasn't it? 2 A. That's correct, sir, a 3 September 25th memo -- or excuse me, September 4 25th, 1990 meeting, we're talking about an 5 October 10th, 1990 memo. 6 Q. And that meeting was a month 7 and a half before November 10th, 1990, the date 8 of this Bouchy memo, isn't it? 9 A. Actually it's November 14th, 10 is the date of the Bouchy memo, so it's a month 11 plus. 12 Q. All right. And this memo that 13 you authored is a month prior to this also, isn't 14 it? 15 A. That's correct, sir. 16 Q. And this is reflective of 17 conversations between the Food and Drug 18 Administration and Lilly employees concerning the 19 subject of Lilly, Prozac and suicide, isn't it? 20 A. One minor modification, it 21 wasn't a discussion, it was a meeting. But yes. 22 Q. A meeting about the issue of 23 Prozac and suicide, wasn't it? 24 A. That's correct, sir. Page 71 1 Q. And read for me what you said 2 on -- beginning with the last sentence of page 3 one. 4 A. Bear with me a second. Last 5 sentence of page one, Doctor Temple commented 6 that any such recommended analyses or studies 7 would be a fail safe, quote unquote, and that FDA 8 does not, quote -- excuse me, that FDA does, 9 quote, not disagree with your, notation, Lilly 10 position that it's, notation, the Teicher 11 observations not a problem, close quote. Do you 12 want me to read the remainder of that, or not? 13 Q. No. 14 A. Okay. 15 Q. So does that refresh your 16 recollection that -- Doctor Temple is who? 17 A. Doctor Temple is the director 18 of the Center for Drug Evaluation and Research, 19 Office One. 20 Q. All right. Big Daddy with the 21 Food and Drug Administration? 22 A. I'm not going to respond to 23 that. 24 Q. A high official in the Food Page 72 1 and Drug Administration, isn't he? 2 A. Yes, sir. 3 Q. And does this refresh your 4 recollection then, Doctor Talbott, about the FDA 5 agreeing with Lilly's position that there wasn't 6 any association with Prozac and suicidality? 7 A. No, it really doesn't, I mean 8 I have absolutely no reason to believe that that 9 wasn't what was said, but I don't recollect the 10 conversation. But I will be glad to respond to 11 what I have written, I'll stand by that. 12 Q. Back in October of 1990, you 13 were writing notes that were reflecting that the 14 FDA was telling you that they didn't disagree 15 with Lilly's position that there wasn't any 16 association between suicidality and Prozac, 17 weren't you? 18 A. I would modify my response 19 slightly. I think I was specific here to talk 20 about the Teicher observations. 21 Q. The Teicher observations -- 22 MR. MYERS: Let him finish. 23 A. And that was an article about 24 it, and I don't remember the exact details of it Page 73 1 now, but that was an article about a small group 2 of patients. And so all I would say is, again, 3 because I can't remember the exact meeting, all I 4 would say is what's written here was that the 5 agency didn't disagree with our position about 6 the Teicher observations. 7 Q. And the Teicher observations 8 were what made it known generally, to the general 9 scientific community, that there might be an 10 association, in Doctor Teicher's opinion, between 11 the taking of Prozac and suicidal ideation and 12 suicide attempts, isn't that correct? 13 MR. MYERS: I object to form only 14 because you asked him two questions. One is 15 whether it made the community available and one 16 is what it said. 17 A. Yes, could you -- I will be 18 glad to give you an answer. 19 Q. Teicher's article was 20 something that caused concern within the 21 scientific community, wasn't it, concerning 22 whether or not Prozac caused suicides and suicide 23 attempts? 24 A. In response to your question, Page 74 1 yes, I think that Teicher's article or any new 2 observations reported in an article caused 3 concern within the medical community about any 4 product. 5 Q. And specifically here 6 Teicher's article was causing concern about 7 Prozac and suicide, wasn't he? 8 A. He wrote about Prozac, yes. 9 Q. And he wrote about suicide 10 too, didn't he? 11 A. His patients allegedly, and I 12 can't remember the details, but his patients 13 allegedly -- if you've got a copy of the article, 14 I will be glad to respond to it. But it was 15 about Fluoxetine and references to suicide, yes. 16 Q. It was the subject of a 17 meeting, Teicher's article, between one, two, 18 three, four, five, six, seven, eight, nine, ten 19 Food and Drug employees, wasn't it? 20 A. I didn't count them, I am 21 willing to accept that, sure. 22 Q. And one, two, three, four, 23 five, six, seven, eight, nine, ten, eleven, 24 twelve, thirteen, fourteen, fifteen Lilly Page 75 1 employees, wasn't it? 2 A. Again, I didn't count them, 3 but I am willing to accept that. 4 Q. So you've got twenty-five 5 people -- 6 MR. MYERS: Objection Paul, let him 7 finish his answer. 8 Q. -- you've got twenty-five 9 people talking about the issue of Prozac and 10 suicidality, don't you, as reflected by your 11 memo? 12 A. Well, you've asked me two 13 questions, Mister Smith. I don't mean to be 14 difficult, but you asked me first if we were 15 talking suicide and Prozac, and then -- first you 16 asked me if we were talking about the Teicher 17 article and then you asked me if we were talking 18 about suicide and Prozac. The Teicher article 19 was mentioned, we talked about our monitoring and 20 our clinical trial analyses. The Teicher article 21 certainly was mentioned. I don't know that the 22 entire meeting was about Teicher, I don't think 23 so, but that was one of the issues discussed in 24 the meeting, yes, sir. Page 76 1 Q. Well, let's go back to the 2 memo and see what it actually says. 3 A. Fair enough. 4 Q. To see what is reflected. It 5 says there, doesn't it, that the FDA spent the 6 balance of the meeting discussing possible data 7 analysis or clinical trial designs which would 8 allow us to test whether or not Teicher's 9 assertions are, in fact, real, doesn't it? 10 A. Oh, it says that, yes, sir. 11 Q. You were trying to be 12 accurate, weren't you, in October when you wrote 13 this memo? 14 A. I try to be accurate 15 everytime, sir. 16 Q. And you don't have any reason 17 to doubt the accuracy of anything said in this 18 memo, do you? 19 A. No, not at all. 20 Q. So this meeting of twenty-five 21 people, fifteen individuals from Lilly and ten 22 individuals from the Food and Drug 23 Administration, concerned the issue of Teicher's 24 article, suicide and Prozac, didn't it? Page 77 1 A. Yes, and monitoring and study 2 design, data analysis, et cetera. The phrase 3 that you mentioned, just so that we have this, 4 you know, fully described, notes there that the 5 FDA spent the balance of the meeting. So that 6 would by and of itself say that not everything in 7 that meeting was spent on that particular issue. 8 I think the original question that got us into 9 this was were we there to talk about the Teicher 10 article, I'm just trying to give you a complete 11 response to that. 12 Q. So maybe the best response 13 that we're going to get is that the Teicher 14 article and the subject of suicide and Prozac was 15 a big part of that meeting? 16 A. It was a significant part and 17 don't ask me for a percentage because I can't -- 18 Q. The first sentence there says, 19 Doctor Zerbe provided a brief verbal overview of 20 the agenda for the meeting and then introduced 21 Doctor Thompson. Is that correct? 22 A. Yes, sir. 23 Q. Do you recall what the agenda 24 for the meeting was? Page 78 1 A. No, I don't sir, I'm sorry. 2 Q. Would there be something 3 written concerning what the agenda for the 4 meeting was? 5 A. Well, there should be an 6 attachment to this, that might give us some idea. 7 Q. There wasn't. 8 A. Okay. Maybe the attachment 9 would have an acetate that had the agenda on it, 10 I don't know, just speculating. I can't recall 11 what the agenda was, I think that was your 12 question. 13 Q. You recall when you prepared 14 this memo that you prepared an attachment, is 15 that right? 16 A. I don't remember that I did, 17 but I say that there is an attachment on here. 18 Q. Do you remember this memo -- I 19 mean this meeting in September, 1990? 20 A. I remember a number of 21 meetings with the Agency, I can't remember 22 anything specifically about this one, sir, I'm 23 sorry. 24 Q. Other than what is reflected Page 79 1 in the memo. 2 A. I have to rely on this, yes. 3 Q. It says, "Attachment 1 4 provides the acetates that Doctor Thompson 5 employed either as a visual aide or as a 6 discussion outline throughout the remainder of 7 the meeting." Do you recall Doctor Thompson 8 presenting some acetates? 9 A. Again, all I can rely on is 10 what's in the memo, I don't have a visual picture 11 of Doctor Thompson being up before a group of 12 people doing acetates, if that's what you're 13 asking me. But the memo says that that's what 14 took place and I have no reason to disbelieve 15 that. 16 Q. Do you remember who called 17 this meeting? 18 A. No. Again, if I can -- give 19 me a second to read through, maybe there is 20 something here. 21 Q. Sure, feel free to refer to 22 the memo freely. 23 A. No, there's nothing in here 24 that would suggest who called it, sir. I don't Page 80 1 recall myself. 2 Q. It appears by virtue of the 3 fact that there was some acetates presented, 4 since there was an agenda and since Doctor 5 Thompson made a presentation, that there at least 6 was some preparation for this meeting on the part 7 of Lilly. 8 A. Is that a question? 9 Q. Yes. 10 A. Yes, agree. 11 Q. Was there a preparation? 12 A. Apparently, because acetates 13 and -- yes, acetates. 14 Q. Do you recall making any other 15 notes, other than these reflected by Exhibit 2, 16 in connection with this meeting? 17 A. No, sir, I don't. 18 Q. Do you recall whether or not 19 you all all flew out there on the Lilly corporate 20 jet or you flew commercial? 21 A. I really don't know. You 22 mentioned earlier that there were fifteen of us, 23 so I'm not sure our plane is big enough to carry 24 all that many people. Page 81 1 Q. You had several Lilly 2 corporate jets in October, 1990, didn't you, 3 Doctor Talbott? 4 A. We had some planes, I don't 5 keep up with the fleet that closely. 6 Q. You got -- you had some 7 corporate jets in October of 1990 that would hold 8 fifteen people, didn't you, Doctor Talbott? 9 A. I really don't know, Mister 10 Smith, I think I answered that earlier. I don't 11 know that one plane would hold fifteen people, I 12 think they're smaller planes. 13 Q. Did you make any other notes 14 in connection with this meeting? 15 A. I don't recall any, sir, no. 16 Q. In reviewing the documents in 17 preparation for this deposition, did you see any 18 other notes that might have been made by you in 19 connection with this September 25th meeting? 20 A. I usually do a draft, I like 21 to work from drafts. 22 Q. A handwritten draft? 23 A. No. It would be typewritten 24 because we use word processer a lot. Page 82 1 Q. What do you do with your 2 drafts? 3 A. I usually file those. 4 Q. Do you have any explanation as 5 to why your draft for this Exhibit 2 was not 6 contained in your documents? 7 A. Could have been an occasion 8 when I didn't do one, or if I did do one, I 9 couldn't speak to why it wouldn't be here. 10 Q. Did you look for a draft of 11 Exhibit 2 when you reviewed the documents I 12 believe on two occasions in connection with this 13 deposition? 14 A. For that specific one, no. I 15 wouldn't go in and look for a draft, per se. I 16 might have seen it, but I don't recall that. 17 There were some drafts in there. 18 Q. Of this meeting? 19 A. I don't remember if it was 20 this one or any of the others we had, sir. I do 21 know -- my testimony is that I do know I recall 22 seeing drafts, okay. 23 Q. I don't know if I ever got the 24 answer to the original question I asked. Do you Page 83 1 recall whether or not Lilly called this meeting 2 or the FDA called this meeting? 3 A. You did ask that question, 4 sir, and my testimony I believe was that I don't 5 recall. And in looking -- we took a minute to 6 read the memo and in going through the memo I 7 didn't see anything that would suggest that, one 8 way or the other. 9 Q. This meeting occurred on 10 September 25th, 1990? 11 A. Just a minute, sir. Yes, 12 that's what it says here. 13 Q. The last paragraph says in the 14 meeting's conclusion -- I'm sorry, the last 15 paragraph on the first page. It says, quote, in 16 the meeting's conclusion, we agreed to review the 17 discussion that had taken place and get back with 18 the FDA with any analysis or study recommendation 19 that we might have. Correct? 20 A. Yes, sir, that's what it says 21 here. 22 Q. In light of that, is it still 23 your testimony that you didn't think that this 24 memo from Doctor Bouchy to Doctor Leigh Thompson Page 84 1 would be something that should be submitted to 2 the Food and Drug Administration? 3 A. Excuse me. I think our 4 discussion earlier this morning was that I didn't 5 believe there was any reportable information in 6 there. 7 Q. So is the answer to my 8 question is, as I phrased it now, in light of the 9 last paragraph of your notes concerning the 10 September 25th, 1990 meeting, don't you -- didn't 11 you feel that it would be helpful to forward the 12 November 14th, 1990 correspondence from Doctor 13 Bouchy to Doctor Leigh Thompson to the Food and 14 Drug Administration? 15 A. No, sir, it's not reportable 16 information and I don't believe that it has 17 anything to do with the data analysis or study 18 recommendations. 19 Q. You didn't think, based on the 20 tone of the meeting in September, 1990, that the 21 Food and Drug Administration would find this 22 question raised by Doctor Bouchy, a Lilly 23 physician in Europe, relevant to the issue of 24 suicide, Prozac and suicidality? Page 85 1 MR. MYERS: Let me object to the form 2 only to the extent I don't know that we've 3 established that Bouchy is a Mister or a Doctor 4 or whatever, a medical doctor, or Ph.D doctor, I 5 don't know that that's been established. 6 A. When we were talking -- in 7 response, I'm responding to your question, when 8 we talked earlier about Mister Bouchy or Doctor 9 Bouchy, I didn't know whether he is a Mister or a 10 Doctor. 11 Q. Regardless of that, what's the 12 answer to my question? 13 A. The answer to your question is 14 I do not think this is reportable information, I 15 don't think it has anything to do with data 16 analysis or study recommendations per the 17 September 25th meeting we had with the agency. 18 Q. Let's go back to Exhibit 2. 19 A. I'm sorry, that's the first 20 memo again? 21 Q. That's your memo -- 22 A. Right. 23 Q. -- concerning the meeting in 24 Rockville, Maryland, with the Food and Drug Page 86 1 Administration. And let's identify some of these 2 people that were there with the FDA, okay, 3 because you list them there. 4 A. Certainly. 5 Q. Doctor Anello? 6 A. Do you want me to give the 7 title? 8 Q. Yes. 9 A. He is from the Department of 10 Statistics there. 11 Q. Is he an M.D. or Ph.D? 12 A. I believe, he's a Ph.D, Mister 13 Smith. 14 Q. Doctor Barash or Barash? 15 A. It's Barash, sir, and he's 16 also from Doctor Anello's department. 17 Q. Do you think he is a 18 statistician? 19 A. I believe he is, sir, yes. 20 Q. Doctor Brecher? 21 A. Again, do you mind me 22 correcting the pronunciations, because it's 23 easier for me. 24 Q. No. Page 87 1 A. Doctor Brecher -- it may help 2 you, too. Doctor Brecher, I believe, is a 3 physician, sir, and from Doctor Leber's 4 department. 5 Q. The department of 6 neuropsychopharmacology? 7 A. I believe the official title 8 is the division of neuropharmochological drug 9 products. 10 Q. Is he senior or junior to 11 Doctor Leber? 12 A. He would be reporting to 13 Doctor Leber. 14 Q. Doctor Graham? 15 A. I believe Doctor Graham is 16 also a statistician associated with Doctor Anello 17 and Doctor Barash. 18 Q. Doctor Laughren? 19 A. Doctor Laughren is one of 20 Doctor Leber's staffers, a physician, I believe. 21 Q. Doctor Leber? 22 A. He's the director of the FDA's 23 division of neuropharmochological drug products. 24 Q. Doctor Levine? Page 88 1 A. I believe that Doctor Levine 2 is a statistician working with Doctor Anello and 3 the other statisticians. 4 Q. Doctor Stadel? 5 A. Yes, Stadel, it's -- is also a 6 statistician with Doctor Anello and Barash, et 7 cetera. 8 Q. Doctor Temple? 9 A. Earlier we talked about Doctor 10 Temple, he's the director of the FDA center of 11 drug evaluation and research, office one. 12 Q. And Mister David? 13 A. Mister David, I believe, is 14 administrative officer working for Doctor Leber. 15 A CSO is the term that they -- consumer safety 16 officer is a term they apply to those folks. 17 Q. CSO? 18 A. CSO, yes, sir. 19 Q. What was his function there? 20 A. He is an administrative 21 person, sets up meetings, make sure they have the 22 room, if they need overhead projectors, make sure 23 it's there. Administrative functions I guess is 24 the best characterization. Page 89 1 Q. Clerical? 2 A. No, I would stay with 3 administrative, I think. 4 Q. You say his title is CSO, 5 consumer safety officer, that implies to me that 6 he might be an individual within the Food and 7 Drug Administration who has as his primary duty 8 evaluating consumer safety and a particular 9 product. Is that not what Mister David's 10 function was there? 11 A. No, sir, my understanding of 12 what a consumer safety officer does is that they 13 provide administrative services, they schedule 14 meetings and make sure that you have rooms, and 15 make sure that you have audiovisual equipment, if 16 you need it, et cetera. I don't believe that the 17 title is really reflective of their day to day 18 duties. 19 Q. Would Doctor Leber or Doctor 20 Temple have been the senior member of the FDA 21 there? 22 A. If you look at the table of 23 organization, Doctor Temple would be, sir. 24 Q. Then it would be Leber? Page 90 1 A. Yes, as we go down, it would 2 be Leber, division director. 3 Q. It says the FDA -- the last 4 part of the last sentence on the first paragraph 5 says the FDA spent the balance of the meeting 6 discussing possible data analysis or clinical 7 trial designs which would allow us to test 8 whether or not the Teicher assertions are in fact 9 real. Doesn't it? 10 A. Yes, it says to test whether 11 the Teicher assertions are in fact real, but 12 otherwise, that is correct. 13 Q. What data analysis was 14 suggested there, Doctor Talbott? 15 A. I don't recall, Mister Smith. 16 Q. Do you remember a specific 17 discussion of particular data analysis? 18 A. No. And in fact, I think my 19 earlier testimony was that I really don't recall 20 this meeting, per se. There were meetings with 21 the FDA, I know that this meeting took place 22 because the memo is here, but about a particular 23 thing that took place in that meeting, I can't 24 say that that took place, or I can't recall, I Page 91 1 don't have a visual picture of it. 2 Q. How many meetings were held 3 between Lilly and the Food and Drug 4 Administration in the calendar year in 1990, in 5 Rockville, Maryland? 6 MR. MYERS: With respect to any drug 7 or any issue? 8 MR. SMITH: Uh-huh, yes. 9 A. Dozens. 10 Q. How many meetings were held 11 with the Food and Drug Administration and Lilly 12 employees concerning Prozac that you were there? 13 MR. MYERS: 1990? 14 MR. SMITH: In 1990. 15 A. Again, the only way I could 16 possibly respond to that is having gone through 17 my documents in preparation for our depositions 18 together, I do remember seeing several 19 memorandums of meetings. Now whether they were 20 1990 or not, I don't know, but there were several 21 meetings in that time frame. Whether they were 22 specifically 1990 or not, I don't recall that. 23 But there were several, I guess would be my 24 response, and some of those may have occurred, in Page 92 1 fact, at least one of them did occur in 1990. 2 Q. My question is, what is your 3 recollection as we sit here today concerning how 4 many meetings were held with the Food and Drug 5 Administration in 1990 where the issue was Prozac 6 and suicide? 7 A. I think I just answered that, 8 sir. 9 Q. Can you recall specifically 10 more than this one? 11 A. No, I don't, I don't. If 12 you've got something to show me, I will be glad 13 to respond to it. 14 Q. Well, do you recall any 15 meetings where you had Doctor Temple and Doctor 16 Leber present and discussed suicide and Prozac in 17 1990, other than this meeting? 18 A. No. 19 Q. In Rockville, Maryland? 20 A. No. 21 Q. This is the only one you 22 recall? 23 A. And the only reason I recall 24 is because we have this memorandum in front of Page 93 1 me. Again, I do not have a mental picture of 2 being in a room at FDA with Bob Temple and Doctor 3 Leber there talking about Prozac, even about this 4 one, but I'm relying on this memo as a true 5 record of what took place. 6 Q. Well, you were the director of 7 medical regulatory affairs at the time this memo 8 was written. 9 A. That's correct, sir. 10 Q. And you were the person at 11 Lilly responsible for seeing that Lilly complied 12 with the Food and Drug Administration regulations 13 in connection with Prozac at this time? 14 A. Yes, sir. 15 Q. But you don't really have any 16 specific recollection of this meeting? 17 A. Not other than what we've got 18 right here. 19 Q. Well, I'm going to ask you 20 some specific questions -- 21 A. Okay. 22 Q. -- about what you've written 23 here. So I want to get as complete an 24 understanding from you as is possible concerning Page 94 1 what happened at this meeting, all right? 2 A. Okay. But you have to 3 understand too, that it will be based on what's 4 written here before us. 5 Q. Okay. If this is all we're 6 going to get, then we'll develop that, but I'm 7 going to have to go through it. 8 A. Okay. 9 Q. Do you recall what possible 10 data analysis was involved in the first 11 paragraph? 12 A. Hang on just a second, Mister 13 Smith. The data analysis references in the last 14 sentence for the first paragraph, right? 15 Q. Yes. 16 A. Okay. No, I don't, sir. 17 Q. Do you know whether any data 18 analysis was ever done? 19 A. Hang on a second. Again, I 20 apologize. No, because this sentence says, if I 21 may, the FDA spent the balance of the meeting 22 discussing possible data analyses or clinical 23 trial designs, so there is really nothing here 24 that speaks to an actual data analysis that was Page 95 1 presented at that meeting. 2 Q. Regardless of that my question 3 is, do you know as we sit here today whether or 4 not any data analyses was run or done to test 5 whether the Teicher assertions are in fact real? 6 A. You mean for this particular 7 meeting? 8 Q. Subsequent to this meeting. 9 Apparently none had been done prior to that, had 10 they? 11 A. I don't know, Mister Smith, 12 that's what I'm trying to say here, I don't 13 really know. 14 Q. You're the director of medical 15 regulatory affairs at the time, not me. You're 16 going to be the one that knows that information. 17 I'm the one that's asking you the questions about 18 it. 19 A. Indeed. 20 Q. So you've got to tell me, I 21 don't know. 22 A. Okay. Why don't you -- would 23 you mind rereading the question? 24 Q. Was there any data analysis Page 96 1 done in connection with this meeting to test 2 whether or not the Teicher assertions are in fact 3 real? 4 A. What I can develop from this 5 is that our position was that the Teicher 6 assertions were not real. And on the basis of 7 that then, knowing Doctor Thompson the way that I 8 do, I know that there would have had to have been 9 some data analysis for him to take that position. 10 Now, can I point to a specific data analysis, per 11 se? No, I can't. 12 Q. My question is -- listen to my 13 question. 14 A. All right. 15 Q. Was there any data analysis 16 done subsequent to this meeting as discussed with 17 the FDA to test whether or not the Teicher 18 assertions were in fact real? 19 A. Subsequent to, being the 20 operative phase? 21 Q. Yes. 22 A. Yes, sir, there were. 23 Q. What data analyses were done? 24 A. Those were data analyses that Page 97 1 I think were fully represented and discussed at 2 the advisory committee meeting, the FDA advisory 3 committee meeting, that occurred, I believe, 4 about a year later, in 1991. 5 Q. Do you know of any other? 6 A. Well, that is -- when I say -- 7 that would be an analyses. If you look at the 8 entire thing it would be comprised, I'm sure, of 9 many different individual analysis. 10 Q. Okay. 11 A. Am I making my point? 12 Q. Uh-huh. 13 A. So that would be the analysis. 14 You asked me about the analysis, that's the 15 analysis. But it's made up of not just a single 16 data point, but many, many, many. 17 Q. Was there a discussion in 18 September of 1990, that there was going to be an 19 advisory committee called to examine this 20 question of whether or not Prozac was related to 21 suicidality, Doctor Talbott? 22 A. At this particular meeting, 23 sir? 24 Q. Yes. Page 98 1 A. I assume there wasn't or we 2 would have put that in there or I would have put 3 that in there. 4 Q. When did you first know that 5 there was going to be an FDA advisory committee 6 meeting convened to specifically examine this 7 issue? 8 A. Probably late summer or so of 9 '91. 10 Q. Before September of '91, when 11 the meeting actually occurred? 12 A. Yes. 13 Q. Do you know, Doctor Talbott, 14 whether or not there were any clinical trial 15 designs done subsequent to this memo which would 16 test whether or not Teicher assertions were in 17 fact real? 18 A. Yes, there were, there were. 19 Q. What clinical trials were 20 designed to test whether or not the Teicher 21 assertions were real? 22 A. There were a number, and I 23 recall this both just from general memory and 24 then also from looking through the documents in Page 99 1 preparation for our deposition today, that Doctor 2 Zerbe, several times, was in contact by phone 3 with FDA talking about trial designs, various 4 trial designs. Enrichment is a term that sticks 5 in my head, I think there was something called an 6 enrichment trial design. I'm not a physician, so 7 I can't speak to the specifics of a clinical 8 trial design, that's not my expertise, but I do 9 recall from general memory and also from the 10 memoranda that I've looked through in preparation 11 for today, that there were those conversations, 12 particularly between Doctor Zerbe and people at 13 FDA. 14 Q. Do you know if there were any 15 specific clinical trials done by Lilly designed 16 to examine the issue of whether or not Prozac 17 causes suicidality? 18 A. That was whether they were 19 conducted or not? 20 MR. SMITH: Read the question. 21 (THE COURT REPORTER READ BACK THE 22 REQUESTED TESTIMONY.) 23 A. No, because I think what 24 happened was by the time that we could have Page 100 1 agreed upon design with FDA and initiated the 2 trials, the advisory committee meeting took place 3 and the results of the advisory committee meeting 4 I think were such that FDA and Lilly felt that no 5 additional studies were needed. 6 Q. What I need from you, Doctor 7 Talbott, is a specific answer to that specific 8 question. I'm going to have to object to 9 everything past no as being nonresponsive. 10 MR. MYERS: Don't worry about that. 11 A. I don't know what that means, 12 Mister Smith. Yes or no is what you're asking 13 for? 14 Q. Yes. 15 A. The answer is no. 16 Q. No, there were no clinical 17 trials designed to test the issue of whether or 18 not Prozac caused suicide? 19 MR. MYERS: Wait a minute. 20 Q. Let me finish my question, 21 please. 22 MR. MYERS: You finish and then I will 23 do my objection. 24 MR. SMITH: It's hard for me to finish Page 101 1 my question when you continue to interrupt me, 2 Counsel. 3 MR. MYERS: I didn't interrupt you, 4 Mister Smith. 5 MR. SMITH: Yes, you did interrupt me. 6 The record will reflect that you interrupted me. 7 MR. MYERS: Don't raise your voice, I 8 can hear you perfectly well. 9 MR. SMITH: I object to it. I guess 10 I'm going to have to raise my voice in order to 11 be able to question this witness without your 12 interrupting me. 13 MR. MYERS: I'm not going to change 14 anything I do, Mister Smith, based on your tone 15 of voice. 16 MR. SMITH: What is your objection? 17 MR. MYERS: Why don't you finish the 18 question and then I'll make my objection. 19 Q. Do you know of any -- or is 20 the answer to your question, there were no 21 clinical trials designed by Eli Lilly and Company 22 to test whether or not Prozac causes suicidality? 23 MR. MYERS: Let me object to the form 24 because he answered the question on design. Your Page 102 1 most recent question before that was were they 2 conducted, so you've now asked another question, 3 Paul, so I object to the form. 4 MR. SMITH: Where? 5 A. Okay. The most recent 6 question, as I understand it was, were there any 7 trials designed. And, yes, there were a number 8 of trials designed based on my earlier discussion 9 where I do recall that there were conversations 10 about trial designs and in preparation for today, 11 I do remember seeing some memoranda of telephone 12 conversations from Doctor Zerbe to various people 13 at FDA talking about trials that we had designed. 14 So, the answer to that is -- to your question is, 15 yes, there were trials designed. 16 Q. Did you -- do you recall 17 seeing any actual protocols that were submitted 18 or done -- that were done or submitted to the FDA 19 concerning these particular trials? 20 A. I don't recall seeing any, 21 sir, no. 22 Q. Do you know what a protocol 23 is, Doctor Talbott? 24 A. Yes, sir, I do. Page 103 1 Q. Is it the requirement of the 2 Food and Drug Administration or is it the policy 3 of Eli Lilly and Company that any protocol for 4 any clinical trial must be submitted and approved 5 by the Food and Drug Administration? 6 A. It's not only our policy, but 7 I think under the IND regulations it's a federal 8 requirement. 9 Q. Did you, as director of 10 medical regulatory affairs for Eli Lilly and 11 Company, ever submit to the FDA any protocol 12 designed to test whether or not there was an 13 association between Prozac and suicidality? 14 A. I don't recall any, but the 15 application file would be a better source because 16 if there were one done it would be in there. But 17 my recollection is that I do not recall one. My 18 answer is that I do not recall one. 19 Q. Do you recall receiving 20 approval from the FDA to do a particular protocol 21 to test whether or not there was a relationship 22 between Prozac and suicidality? 23 A. No, sir, I don't. 24 Q. Now, as I understand it, even Page 104 1 though there may have been some design of some 2 clinical trials to test this, there was in fact 3 never actually any clinical trials done to test 4 this, is that correct? 5 A. That's correct, sir. 6 Q. Did you ever -- do you recall 7 as director of medical regulatory affairs ever 8 requesting permission from the Food and Drug 9 Administration to not conduct a clinical trial 10 designed to test the issue of whether or not 11 Prozac caused individuals to become suicidal? 12 A. Do you mind reading that back? 13 (THE COURT REPORTER READ BACK THE 14 REQUESTED TESTIMONY.) 15 A. No. 16 Q. Do you know of any clinical 17 trial experience at all, Doctor Talbott, that was 18 designed to test the issue of whether or not 19 Prozac causes people to become suicidal? 20 A. Well, the clinical trial 21 experience that led to the new drug application 22 was a real life use situation of Prozac, and so -- 23 I'm sorry, did I misunderstood your question? 24 Q. Yes, because my question was, Page 105 1 clinical trials that were designed to test this 2 question. 3 A. Specifically for that 4 question? 5 Q. Yes. 6 A. No. 7 Q. Well, do you know whether or 8 not as director of medical regulatory affairs any 9 of the protocols that were actually done as 10 clinical trials had as a part of that protocol 11 the specific examination of the question of 12 whether or not ingestion of Fluoxetine caused 13 suicidal ideation by depressed individuals? 14 A. Specifically, no, I do not. 15 Q. Do you know of any trials in 16 the entire clinical trial experience that were 17 conducted to test or to use Prozac to treat 18 people who were suicidal? 19 A. Again, you're starting to 20 press the level of my expertise here and I will 21 answer on the basis of understanding that I am 22 not a physician and that's starting to get very 23 clinically specific. But I don't, in my position 24 as medical regulatory affairs director, do not Page 106 1 recall any such trials. 2 Q. Do you know Doctor Stuart 3 Montgomery in England? 4 A. I've heard of Doctor 5 Montgomery, but I don't know him. 6 Q. Do you know what trials he did 7 in England in '88 or '90? 8 A. No, I don't. 9 Q. Do you know whether or not he 10 did any trials in England in '88 or '90? 11 A. I know he was a clinical 12 investigator for us, but the timeframe I couldn't 13 speak to. 14 Q. Do you know whether or not, as 15 director of medical regulatory affairs, you 16 passed on any information to the Food and Drug 17 Administration concerning any clinical trials 18 done by Doctor Stuart Montgomery? 19 A. Again, these volumes are three 20 and four hundred and five hundred volumes in 21 length, so I can't recall specifically about 22 Doctor Montgomery or not. 23 Q. Let's move to the second 24 paragraph of your memo. Page 107 1 A. Uh-huh. 2 Q. The first sentence of that 3 second paragraph says, the limitations of small 4 enrichment rechallenge studies, as well as large 5 prospective randomized studies were reviewed by 6 all participants. Correct? 7 A. That's what it says, sir, yes. 8 Q. Are you talking about two 9 specific types of studies there in that sentence? 10 I can't really tell for sure. 11 A. Well, let's see. I think 12 primarily we were talking about limitations, both 13 of a small enrichment rechallenge type of study, 14 as well as the limitations of of a large 15 prospective randomized study. 16 Q. So the subject there is you're 17 talking about the limitations that two particular 18 study designs might have? 19 A. That's correct, sir, yes. 20 Q. Do you recall what those 21 limitations were? 22 A. No, I do not. 23 Q. The next sentence there says, 24 the Food and Drug Administration did not request Page 108 1 any action from Lilly nor did the agency suggest 2 a particular analytical or study approach. Is 3 that right? 4 A. That's what it says here, yes. 5 Q. Did anybody at the Food and 6 Drug Administration ever advise you as to why 7 they weren't, the Food and Drug Administration 8 wasn't requesting any action from Lilly? 9 A. No. 10 Q. Did anybody from the Food and 11 Drug Administration ever explain to you why there 12 wasn't a particular analysis that they wanted on 13 this problem? 14 A. No, sir. 15 Q. Did anybody from the Food and 16 Drug Administration ever explain to you why they 17 didn't want a particular study approach done to 18 this particular situation? 19 A. No, sir. 20 Q. The last sentence on page one 21 says, and continued on to page two says, Doctor 22 Temple commented that any such recommended 23 analyses or studies would be a "fail safe" and 24 that the FDA does not disagree with Lilly -- with Page 109 1 your [Lilly] position that it's 2 [the Teicher observations] not a problem, end of 3 quote. Correct? 4 A. That's correct, sir, that's 5 what it says. 6 Q. So was it your judgment, as 7 director of medical regulatory affairs at that 8 meeting that the Food and Drug Administration had 9 already come to the conclusion that Teicher's 10 observation about Prozac and suicide was not a 11 problem? 12 A. Based on this sentence, it 13 would appear that the agency, at least at that 14 time, was in agreement with our position, 15 preliminarily, that it was not a problem. So, 16 the answer to your question is the agency agreed 17 that there was not a problem at that time, yes, 18 they agreed. 19 Q. And that the only reason they 20 were wanting data was so that there would be a 21 fail safe -- you use the specific term fail safe. 22 A. Yes. Let me tell you how I 23 would use that. That would be a situation where 24 you would want, and whether it applies to this or Page 110 1 any other situation, where you would want to 2 continue to investigate a problem or an issue or 3 an item until you had total, positive, one 4 hundred and five percent proof that there wasn't 5 a problem, a fail safe. That's how I use that 6 term. 7 Q. Did Doctor -- you said Doctor 8 Temple commented that any such recommended 9 analyses or studies would be a fail safe? 10 A. Uh-huh. 11 Q. Was the term "fail safe" your 12 term, or are you quoting Doctor Temple in this 13 memo? 14 A. I would think, that if I put 15 quotes around it, it was probably -- again, 16 Mister Smith, it's been nearly four years. I 17 can't remember Bob Temple saying fail safe, but 18 relying on this, putting the quotes around it, I 19 would -- that the indication to me that that's 20 what he said. Those two terms, because if I may 21 continue, because I was very careful to continue 22 there with quotes shortly thereafter. 23 Q. That what my next question was 24 going to be. It appears that you are actually Page 111 1 trying to quote what Doctor Temple actually said 2 and that he said the studies would be a, quote, 3 fail safe, end quote, and that the FDA does not, 4 quote, not disagree with your [Lilly] position 5 that it's the Teicher -- that it's -- and then 6 you put in parentheses the Teicher observations 7 not a problem. Correct? 8 A. That is correct, sir. 9 Q. So are you meaning to quote 10 Doctor Temple to be saying that he doesn't think 11 that Doctor Teicher's observations concerning 12 Fluoxetine and suicide are a problem, is that 13 what you intended to attribute to Doctor Temple 14 by virtue of your using the quotes? 15 A. My general practice, Mister 16 Smith, and again, I can't remember the meeting, 17 so I clearly couldn't remember a quote. But my 18 general practice is, and this was written not too 19 shortly thereafter, my general practice then was 20 if somebody said a specific word, to the best of 21 my recollection I would try to quote it, 22 especially when it includes sort of a statement 23 as this is. 24 Q. And you were probably taking Page 112 1 written notes during the course of this? 2 A. My practice is to take just 3 very sketchy notes. 4 Q. But is it your practice to 5 have those sketchy notes in front of you when you 6 dictate a more complete memo of a particular 7 meeting or conversation? 8 A. That's correct, sir. 9 Q. And do you think that you 10 might have even written down in your own 11 handwriting these terms that you attribute to 12 Doctor Temple? 13 A. I could very easily have, yes, 14 sir. 15 Q. You go on to say there in your 16 memo, after a few minutes general discussion 17 about CNS compound development [Note: Doctor 18 Leber implied that a cholinomimetic agent was 19 experiencing some difficulties in trials]. What 20 is cholinomimetic, am I even pronouncing it 21 right? 22 A. Pretty good. Cholinomimetic, 23 I'm going back to grad school here, it would be a 24 compound that mimiced, that's why you have Page 113 1 mimetic in there, that mimiced the action of 2 acetylcholine. 3 Q. You say it's a CNS compound, 4 is that right? 5 A. Central nervous system, yes, 6 sir. 7 Q. Like Prozac is a CNS compound? 8 A. It is an anti-depressant, yes. 9 Q. Is cholinomimetic agent an 10 anti-depressant agent also? 11 A. I don't know, because Doctor 12 Leber didn't say anything more than that. 13 Q. He said there was some other 14 agent that was experiencing some difficulties in 15 trials, correct? 16 A. That's what it appears here, 17 yes. 18 Q. Can you give us more 19 information about what that agent was -- you 20 don't know? 21 A. No, sir, I don't recall it. 22 Q. You don't know whether it was 23 another anti-depressant or not? 24 A. No, Mister Smith, I don't. Page 114 1 Q. You don't know if it was 2 another product manufactured by Lilly? 3 A. Oh, had it been another 4 product by Lilly, we would have made a comment to 5 that effect, I would have put it here. 6 Q. Was it the policy of the Food 7 and Drug Administration to discuss status of 8 clinical trials on other pharmaceutical firms' 9 products, Doctor Talbott? 10 A. I wouldn't presume to speak 11 for what the agency policy was, all I know here 12 is from the looks of it, there was no compound 13 mentioned, there was no indication mentioned, 14 there was no manufacturer mentioned, and I think 15 probably what Doctor Leber was just talking about 16 were some general pharmacological observations. 17 I don't believe that any, at least as I 18 understand it, confidentiality thresholds were 19 breached on this. 20 Q. Well, you don't mention any 21 other manufacturer or any other trial, do you? 22 A. No. 23 Q. But you say you don't have a 24 recollection of the discussion other than what Page 115 1 you've written down there? 2 A. No, that's exactly right, sir. 3 Q. So he could have mentioned 4 some other pharmaceutical manufacturer, some 5 other compound, and you might have had some 6 details about what this compound was. 7 A. Again, my -- and all I can go 8 on is what my general process was on these 9 meetings, and I do believe that had he given more 10 specifics on this that I would have reported 11 them. 12 Q. But your memo indicates that 13 Doctor Leber, who was at that time -- what was 14 his position? 15 A. He was the director of the 16 division of neuropharmacological drug products. 17 Q. Doctor Leber was, as the 18 director of the division of neuropharmacological 19 drug products, was advising I believe it was 20 fifteen members of Eli Lilly and Company that 21 there was another product that was having 22 problems in clinical trials that were ongoing and 23 that it was a CNS product? 24 A. Let me read it again. Well, Page 116 1 what I stated here was, we were talking, as you 2 know we have an extensive development program for 3 central nervous drugs, we were in general 4 discussion about these compounds' development, 5 and I state here Doctor Leber implied. So at 6 least my use of the term imply means that I am 7 drawing an inference based on loose information. 8 Again that fits with what I just said earlier, 9 had there been anything specific, i.e. a 10 particular chemical mentioned or drug, a 11 manufacturer, even an area of therapy, then I 12 believe I would have put it down. 13 Q. Was Doctor Leber in the habit 14 of giving Lilly employees loose information 15 concerning the status of clinical trials on other 16 products? 17 A. Oh, I wouldn't even respond to 18 that, sir, the way the question is phrased. 19 Q. You were the one that used the 20 term loose information, that's the reason I 21 phrased it that way, Doctor Talbott. 22 A. I apologize. I don't think I 23 used it in relationship to something Doctor Leber 24 would do, did I? Page 117 1 MR. SMITH: Would you read his answer 2 back? 3 MR. MYERS: And the question. 4 (THE COURT REPORTER READ BACK THE 5 REQUESTED TESTIMONY.) 6 A. I apologize, Mister Smith, I 7 did use that term. I don't mean that to refer to 8 Doctor Leber in any way at all, it would be a 9 gross mischaracterization. So, I withdraw the 10 use of that term, I'm sorry. General information 11 would be a more appropriate way rather than 12 loose, it was a misstatement. 13 Q. The difficulties that this 14 other agent was experiencing you say was in 15 trials? 16 A. Let's see here, that was my 17 inference, yes, was experiencing some 18 difficulties in trials. 19 Q. Were you talking about 20 clinical trials in humans? 21 A. Yes, sir, I think that's what 22 the implication is, sir. 23 Q. So, is it your recollection 24 that this is potentially another compound Page 118 1 manufactured by a competitor as opposed to a 2 Lilly product, because you would have, had it 3 been a Lilly product, specifically noted that? 4 A. Sure, we would have known 5 about it, but I'm not sure it would have been 6 another manufacturer. Because as I'm sure you 7 know, the agency actually has investigation of 8 new drug applications, has more investigation of 9 new drug applications from individual physician 10 investigators than they do from pharmaceutical 11 firms. 12 Q. Well, whether -- from some 13 other individual or company. 14 MR. MYERS: Other than Lilly? 15 MR. SMITH: Other than Lilly. 16 A. Yes. 17 Q. Now, the next part of that 18 sentence says -- well, I'm going to try to read 19 it in context if I can. It says, after a few 20 minutes of general discussion about CNS compound 21 development, then can we take out what's in 22 paren? 23 A. Well, as long as we're not -- 24 I don't know the legal niceties, but just for our Page 119 1 discussion here? 2 Q. Yes. I'm trying get some 3 sense of what you're saying when you say that 4 Doctor Leber, or you, or somebody is saying, 5 quote, and the impact of a possible operating 6 fund sequestration. 7 A. Okay. Was there a question 8 there? 9 Q. Yes. I don't know what that 10 impact of possible operating fund sequestration 11 goes with in the sentence, I guess is my 12 question. 13 A. I understand. 14 Q. Can you help me on what that 15 goes with? 16 A. Let me see if I can -- because 17 this is based on some understanding of FDA and 18 how they're funded. This was in September or 19 October, and invariably, the FDA budgets are not 20 presented to Congress in time for the budgets to 21 go past the end of the physical year and continue 22 to fund operations and apparently from what 23 they're saying here, there was some sequestration 24 of continuing funds that would bridge them over Page 120 1 this time until Congress could pass their 2 authorization that they were talking about, and 3 that fund apparently had been sequestered. I 4 don't know what the politics or what the 5 governmental situation or what the funding 6 authorization was at that time, but I think 7 that's what that's referring to. It doesn't have 8 anything at all to do with CNS product 9 development. 10 Q. It's in the same sentence. 11 A. It was just a wrap sentence, a 12 wrap up. I would state categorically it has 13 absolutely nothing to do with CNS compound 14 development. 15 Q. Well, it says -- if you take 16 out what you have in parentheses there. 17 A. Uh-huh. 18 Q. The sentence would read, after 19 a few minutes general discussion about CNS 20 compound development and the impact of possible 21 operating fund sequestration, the meeting was 22 concluded. 23 A. Uh-huh, that's what it says, 24 sir. Page 121 1 Q. Would that be the more 2 accurate way to put it, and just leave out this 3 problem that this other agent was having in 4 connection with its clinical trials? 5 MR. MYERS: Let me object to the form, 6 to the extent you say make it more accurate. As 7 opposed to what, as opposed to if you left the 8 brackets in? 9 MR. SMITH: Yes, in understanding the 10 sense of what was going on there at that meeting. 11 A. Mister Smith, I'm really not 12 following this. I'm sorry, sir. 13 Q. What I don't understand, I 14 have never heard of operating funds in connection 15 with the FDA and its operation. And I didn't 16 understand why the question of funding would be 17 mentioned in a memo that you, as the director of 18 medical regulatory affairs would be having in 19 this group, in this meeting of twenty-five 20 individuals with Lilly and the Food and Drug 21 Administration. Why are you talking about in 22 this memo operating fund sequestration? 23 A. Well, it's very pertinent 24 because, as happens generally every year when Page 122 1 these authorization bills come up and get put 2 off, et cetera, and again I don't remember the 3 exact politics of what was happening back in 4 1990, but the agency has on occasion actually 5 furloughed people, sent them home from work, 6 until they got additional funds to operate on. 7 Either whether they got new authorizations or 8 they had continuing funds or operating funds 9 taken over, apparently someone in government 10 sequestered the operating funds that would tide 11 them over this authorization break, and it had a 12 lot -- it has a lot of importance to me as a 13 regulatory person because that might mean that 14 there are very few people at the agency for the 15 two or three weeks that are to take place there. 16 I don't think this happened, I don't think that's 17 ever occurred, at least during modern times where 18 people have been furloughed, I think that 19 happened back in the early '70's. So I think 20 that's why I put it in here so that people who 21 would read this would understand there was a 22 potential hiatus at the agency. Now, that didn't 23 happen, I don't think that's happened during my 24 professional lifetime. That's the best I can do. Page 123 1 Q. Is it your testimony that the 2 impact of the possible operating fund 3 sequestration doesn't have anything to do with 4 this discussion about this other CNS compound and 5 about the fact that that other CNS agent was 6 experiencing difficulties in trial? 7 A. That is my testimony, sir, 8 yes. 9 Q. So, is it that -- the 10 operating fund that you are mentioning, is an 11 operating fund that the FDA had? 12 A. The government had, yes. 13 Q. That the government had? 14 A. Yes. 15 Q. Well, it was an operating fund 16 that the FDA had to operate. 17 A. Right. 18 Q. Correct? 19 A. And, I believe, the FDA is 20 also funded along with the Department of 21 Agriculture, so the operating fund would probably 22 apply to both areas. 23 Q. So late in the year, October -- 24 I mean September of 1990, when the ten FDA Page 124 1 employees and the fifteen Lilly employees were 2 talking about the possible problems of Fluoxetine 3 and suicide, they were also talking about the 4 possible problem of funding for the FDA for the 5 end of the year, is that what you're saying? 6 A. Let's remember the sentence 7 that that comes in, general discussion, it was a 8 concluding discussion. 9 Q. I understand that. 10 A. This statement, as I wrote it 11 here, I stand by. It took place at this meeting. 12 That's my record, I stand by what's written. 13 Q. So, to make sure I understand, 14 the operating fund you're talking about in this 15 memo of October 10th, 1990, Exhibit 2 of your 16 deposition, is operating funds of the Food and 17 Drug Administration? 18 A. And the Agriculture Department 19 as I mentioned. Because they're funded -- I 20 don't know why, but they're funded together. 21 Q. And there was some 22 sequestration of funds? 23 A. Apparently, somebody in the 24 government had tied up the funds that would Page 125 1 normally be used to tide over during the break in 2 the authorization as people on the hill debated. 3 And now I'm getting into Washington politics, I'm 4 outside of my element certainly. But as I 5 understand it from past experience, was people on 6 the hill debated authorization and sometimes 7 there is a hiatus on actual authorization of 8 funds so that there is a carry-over of operating 9 fund or continuation fund and that's -- 10 apparently here someone sequestered it. 11 Q. So, it wasn't that the FDA was 12 running out of money, it was that somebody took 13 away money that they thought they would have to 14 operate on? 15 A. I'm not sure they took it 16 away, sequester means to me just to hold tight, 17 not to let out. 18 Q. Make available -- make it not 19 available, make that money not available for use? 20 A. Right, the possible occurrence 21 of that, right. 22 Q. This is taxpayers' money? 23 A. I don't know, Mister Smith. 24 Q. It's money -- it's government Page 126 1 money that's going to be -- that the FDA had 2 budgeted to use, is that right? 3 A. That's my understanding. And 4 again, we're really starting to get on the edge 5 of what I understand about government operations, 6 okay. 7 Q. Well, you worked for the 8 government, specifically you worked for the Food 9 and Drug Administration for a few years. 10 A. I think that's in testimony, 11 yes, sir. 12 Q. Since you've been with Eli 13 Lilly and Company, you've dealt with the 14 government, the Food and Drug Administration ever 15 since this nineteen, what -- 1982? 16 A. That's correct, sir. 17 Q. So was the government -- was 18 the FDA running out of money, or was -- I don't 19 understand the impact, and you say it's 20 important, the impact on what this would have had 21 on either the FDA or Lilly. 22 MR. MYERS: Before he answers, let me 23 object to the form and to the continued line of 24 questioning. Paul, he's told you what he knows Page 127 1 about this, move on to something else. He's 2 explained as much as he knows from what he wrote. 3 Tell him one more time, Doctor Talbott. 4 A. To the best of my 5 understanding, and again I'm not an expert on 6 government funding, but there had been a time 7 back in the very early '70's or late '60's -- 8 Q. We're talking about -- 9 MR. MYERS: Wait a second, let him 10 answer. Let him answer, Paul, you've asked him. 11 MR. SMITH: I apologize. 12 A. That's all right, no problem. 13 In the late '60's or early '70's, when there was 14 a funding hiatus, and there were actually some 15 people at FDA that were sent home, not everybody, 16 functions continued. But there were some people 17 sent home for a few days until the authorization 18 took place again. When I was at FDA that was 19 part of the lore there, that's how I learned of 20 it. I didn't recall from actual first-hand 21 information, but people talked about that. And 22 so it was important to me because there was a 23 potential of that happening again if these 24 bridging funds were not unsequestered. And based Page 128 1 on this, and this was prior to October 1, I think 2 the fiscal year starts October 1, this was 3 September 25th. So, as is sometimes the case, 4 there was talk of that possibility happening. 5 And apparently the funds were sequestered by 6 somebody in the government, for what purpose I 7 don't know, but the agency mentioned that. And 8 so we, in wrapping up this meeting -- it was in 9 the news I'm sure, we talked to the agency, 10 mentioned to the agency, they mentioned it to us 11 and that was it. It had nothing to do with CNS 12 compound development at all, it was general 13 discussion about agency operations. And that's 14 the best I can do for you, sir. 15 Q. What impact -- you used the 16 word impact of possible operating fund 17 sequestration, what impact would this have had? 18 A. If it hadn't been resolved, 19 probably what happened as I mentioned earlier in 20 my last question or answer, what happened back in 21 the late '60's or '70's, whenever they did that 22 furlough would have taken place. But that's not 23 occurred since then, I do know enough about FDA 24 operating history to know that has not occurred Page 129 1 since then. So, apparently some resolution was 2 met in the government. 3 Q. Was this operating fund 4 sequestration going to hold off approval of other 5 Lilly products? 6 A. I don't think approval of any 7 products were talked about. 8 Q. So, were the FDA employees 9 there, did they express they were worried about 10 being furloughed? 11 A. No, I don't -- I can't recall. 12 Because I think if they had said something like 13 that, I might have put it in there. I think they 14 just -- there was very, probably very specific, 15 just factual commentary about what -- apparently 16 there had been talk about possible sequestration, 17 I'm not sure that took place or not, but it was 18 just general discussion. You know, if you can 19 ask me some other -- I feel like I'm answering 20 the same thing over and over again, I'll be glad 21 to continue that, but I can't give you any more 22 information on it. 23 Q. Would the -- when you used the 24 word impact of possible operating fund Page 130 1 sequestration, would operating fund sequestration 2 impact any of the FDA's analysis of the 3 relationship between suicide and use of Prozac? 4 A. I don't know. 5 Q. Could it have? 6 A. I don't know, it didn't 7 happen. 8 Q. All right. But was that 9 discussed? 10 A. No, not to my recollection. 11 If it had been, I would have put it in there. 12 Again, this is just general conversation, almost 13 like the weather. In this case, it happened to 14 do with something that impacted the agency. It 15 was in the government operations, it was in the 16 news. In Washington, authorizations every year 17 are big news items, I think that's probably why 18 this was brought up. Kind of like the Redskins. 19 Q. Kind of like what? 20 A. I know, I should have said the 21 Cowboys, but actually the Redskins. 22 MR. SMITH: Redskins aren't a big deal 23 in Dallas. 24 Q. Were there problems within the Page 131 1 Food and Drug Administration, that you recall, 2 that would have caused this operating fund 3 sequestration? 4 A. No, sir, I don't think it had 5 anything at all to do with the FDA. 6 Q. The FDA wasn't criticized, 7 some congressman wasn't after the FDA at a 8 particular time? 9 A. I don't recall that, no. 10 Probably if that had been linked to it, I think I 11 would have put that in, like Congressman X was 12 sequestrating funds or something. 13 Q. Was the Food and Drug 14 Administration on a short budget -- 15 A. I don't recall, Mister Smith. 16 Q. -- in September of 1990? 17 A. I'm sorry, I didn't mean to 18 interrupt. Would you repeat it, I walked all 19 over your question. 20 Q. Was the Food and Drug 21 Administration on a short budget in September of 22 1990? 23 A. I don't know, sir. 24 Q. Well, is that what you mean to Page 132 1 imply by when you say the impact of the possible 2 operating fund sequestration? 3 A. Again, the federal government, 4 including FDA, is funded, I think, from October 1 5 to the last day of September, and so funding is 6 done on a yearly basis. So I don't think they 7 were on short budget, I think all of this 8 question came out of whether there was going to 9 be authorization for a new federal government 10 budget after that time. 11 Q. It's been said of the Food and 12 Drug Administration that they're understaffed, 13 underfunded, and that the individuals there are 14 overworked. Would you agree with that analysis 15 based on your experience in the FDA and your 16 experience in dealing with the Food and Drug 17 Administration while at Eli Lilly and Company? 18 A. That was both my FDA 19 experience and my Lilly experience? 20 Q. Yes, sir. 21 A. I would say that in some areas 22 of the agency that's true, yes. 23 Q. Would you say it's true of the 24 neuropsychopharmacological division? Page 133 1 A. If I may correct you, sir, the 2 division of neuropharmacological drug products. 3 Q. All right. 4 A. No. 5 Q. Why, they had plenty of money? 6 A. I don't know about the money, 7 but -- 8 MR. MYERS: Let him finish. Let him 9 finish. 10 Q. They're not under-funded? 11 A. All I know is they seem to 12 have a number of staff, they're very competent 13 people. I don't know that I'd characterize that 14 division that way at all. I think they seem to 15 be adequately staffed, very good staff in fact. 16 Q. So they had plenty of people? 17 A. I said they were adequately 18 staffed, I think I'll stick with that. 19 Q. Is it your testimony that 20 since you've been dealing with them since 1982, 21 you had never experienced difficulty in the FDA 22 having enough time or people to deal with 23 particular problems or drugs that Lilly had 24 presented to them for review? Page 134 1 A. Well, I need to -- did you say 2 FDA or this particular division, I can't recall? 3 Q. This particular -- if I said 4 FDA, I meant this particular division. 5 A. I believe you said this, and I 6 only really have been interacting with the 7 neuropharm division since 1985. I think you 8 mentioned 1982. So in this particular division, 9 since 1985, they've always seemed to have 10 adequate staffing. 11 Q. So you wouldn't agree that 12 they were overworked, this division? 13 A. I have not seen any evidence 14 that this division is understaffed at all. 15 Q. All right. Would you then 16 disagree that this division is overworked? 17 A. Well, all I can say is the 18 evidence that I have seen and they have done -- 19 they have very, very superb staff, adequately 20 peopled, they have done very careful evaluations 21 of our applications that have been down there, I 22 think that their science, at least insofar as I 23 can judge the scientific aspects of it, has been 24 impeccable. All overt signs I think show that Page 135 1 they are -- I won't characterize it overworked, 2 but I think that they're adequately staffed. I 3 really don't know what overworked means, I guess 4 is what I am saying. 5 Q. That they don't have enough 6 time, enough hours during the day to do the work 7 that they have to do because of there is just so 8 much work, that can go to so many people. 9 A. I think that they perform 10 excellently in all the reviews that they've had. 11 I think they're adequately staffed. 12 Q. I'm not asking you to 13 criticize them or pat them on the back, Doctor 14 Talbott. 15 A. I know. 16 Q. I just want to know what your 17 observations are concerning whether or not there 18 appears to be enough people in this division to 19 do the job that Congress intends for them to do? 20 A. With the caveat that I would 21 not presume to say what Congress's intent is on 22 this or any other matter, there are adequate 23 people in this division to do the job, yes. 24 Q. Well, with respect to this Page 136 1 division, is it your feeling that the Food and 2 Drug Administration in this division is 3 responsible to ensure the safety of CNS compounds 4 consumed by the public? 5 A. In addition to many other 6 neuropharmacological compounds, yes, sir. 7 Q. Of which Prozac is one? 8 A. That's correct, sir. 9 Q. Do you know of any independent 10 tests done by the Food and Drug Administration 11 and the particular division responsible for, on 12 Prozac for any purpose? 13 A. Yes, sir, I do. 14 Q. All right. Tell me what tests 15 the FDA engaged in, actually performed. 16 A. The division, the statistical 17 division and I apologize because they've changed 18 their name and I'm not sure exactly what their 19 current name is, but the statistical division 20 that we referred to earlier with Doctor Anello 21 and Doctor Barash, et cetera, conducted analyses 22 and these analyses were presented at the advisory 23 committee meeting in the fall of 1991. 24 Q. Now what analysis was the Page 137 1 statistical division at the FDA making? Were 2 they reviewing clinical trials, were they 3 reviewing adverse experience, that is 1639 data, 4 or were they reviewing other material? 5 A. I believe they were reviewing 6 all types of materials, sir, with the possible 7 exception, if I may, the possible exception of 8 animal data. 9 Q. A lot of that data that the 10 statisticians analyzed was data submitted to them 11 by Eli Lilly and Company, wasn't it? 12 A. Some of the data. I can't 13 characterize what their source of data was really 14 because they have their spontaneous adverse event 15 reporting system. 16 Q. All the clinical trial data 17 would have been submitted to the Food and Drug 18 Administration from Lilly, wouldn't it? 19 A. No, I don't agree with that. 20 Q. Well, all the clinical report 21 forms were submitted by Lilly to the FDA, weren't 22 they? 23 A. The clinical report forms, as 24 part of the IND studies which supported the NDA, Page 138 1 were submitted by us, yes. 2 Q. The clinical report forms were 3 filled out by investigators or investigator staff 4 that were selected by Lilly, weren't they? 5 A. They were retained by Lilly, 6 yes. 7 Q. Paid by Lilly, correct? 8 A. They were reimbursed by Lilly. 9 You're getting into an area of clinical trial 10 funding that I really don't know much about. 11 Q. The clinical trial 12 investigators on Prozac, Doctor Talbott, were 13 paid by Eli Lilly and Company to do their 14 investigation, weren't they? 15 A. Yes. 16 Q. And the case report forms that 17 they generated were forms that were designed by 18 Lilly, weren't they? 19 A. Some were. I think some were 20 actually designed by the investigators 21 themselves. 22 Q. If the case report forms were 23 designed by the investigators, those forms had to 24 be -- the design of those forms had to be Page 139 1 approved by Lilly, didn't they? 2 A. By Lilly and the FDA, that's 3 correct. 4 Q. And the protocols that the 5 clinical trials were conducted under, were done 6 by -- were designed by people at Lilly, weren't 7 they? 8 A. Designed by people at Lilly, 9 submitted and approved by FDA, that's correct. 10 Q. I'm not talking about 11 approval. They were designed by people at Lilly, 12 weren't they, the protocols? 13 A. Sometimes with consultation by 14 FDA. 15 Q. But the design came from 16 Lilly, didn't it? 17 A. Eventually we were the ones 18 that had to submit, that's correct. 19 Q. So, the analysis of the 20 clinical trial experience that the statisticians 21 made after approval of the drug and at the FDA 22 advisory committee meeting in September of 1991, 23 was done in part based on clinical trial material 24 supplied by Lilly, wasn't it? Page 140 1 A. That's correct, sir. But if I 2 may, I think your original question was was all 3 of this data from Lilly and I said no, it isn't. 4 You asked me if I agreed and I said no, it wasn't 5 all. And I think you now indicated that it 6 wasn't part from Lilly, that's correct. 7 Q. A large part of it was from 8 Lilly, wasn't it? 9 MR. MYERS: Which data? 10 MR. SMITH: All the data, a large part 11 of it was from Lilly. 12 A. A significant portion was, 13 yes. 14 Q. What other independent test 15 was done by the FDA concerning the approval of 16 Prozac? 17 A. I'm sorry, sir, can you 18 rephrase that, because we were talking about 19 post-approval and now you're talking preapproval. 20 Q. I phrased that wrong. With -- 21 and let me back up a little bit. Did the Food 22 and Drug Administration do any testing on Prozac 23 prior to it being approved for sale to the public 24 in the United States? Page 141 1 A. I don't know that the agency 2 has on this or any other compound. 3 Q. My question is with respect to 4 Prozac, listen to my question. 5 A. All right. 6 Q. Did the Food and Drug 7 Administration do any testing on Prozac prior to 8 it being approved for sale to citizens of the 9 United States? 10 A. Can I ask you to help me with 11 testing, what do you mean by that? 12 Q. Testing of any kind. 13 A. You mean like statistical 14 testing? 15 MS. ZETTLER: Clinical trials. 16 Q. Any testing? 17 A. Yes, in response to that, yes. 18 Q. In response to what? 19 A. In response to did the Food 20 and Drug Administration conduct any testing on 21 Prozac, et cetera, et cetera, prior to approval. 22 Q. What did they test? 23 A. I'm sure there were -- in 24 fact, I know there were statistical analyses and Page 142 1 tests done on data. 2 Q. The statistical analysis and 3 tests on data were done on data and statistics 4 drawn from the clinical trials, weren't they, 5 Doctor Talbott? 6 A. On data drawn from the 7 clinical trials. 8 Q. All right, correct. 9 A. Right. 10 Q. And the data drawn from the 11 clinical trials, as we said earlier, was data 12 supplied by Lilly, wasn't it? 13 A. Yes, for the NDA approval. 14 That's correct, sir. 15 Q. So I'm talking about any 16 independent test, take out the clinical trial 17 statistical analysis that the FDA made of the 18 statistics that were submitted by Lilly in the 19 clinical trials, were there any independent tests 20 done by the Food and Drug Administration on 21 Prozac, Fluoxetine Hydrochloride? 22 A. And you've excluded 23 statistical testing of all the clinical data? 24 Q. Yes, because it was submitted Page 143 1 by Lilly. 2 A. For the NDA approval. 3 Q. Yes. 4 A. Now we're just talking about 5 the NDA approval itself now? 6 Q. Yes. 7 A. I believe your question was, 8 was there any other testing done with the caveat 9 that the statistical data were being excluded 10 from this consideration? 11 Q. Uh-huh. 12 A. The answer is, to my 13 understanding, no. 14 Q. After the NDA approval, in 15 what was it December, 1987? 16 A. I believe it was, sir, yes. 17 Q. Did the Food and Drug 18 Administration do any independent testing on 19 Fluoxetine-Prozac? 20 A. Yes, they did. 21 Q. What? 22 A. Again, I think Doctor Stadel, 23 in fact, who we mentioned earlier, conducted a 24 very thorough statistical analysis of the data, Page 144 1 clinical data. 2 Q. And now is that what you're 3 talking about in connection with this advisory 4 committee meeting? 5 A. Yes, the one you mentioned in 6 September of '91, yes. 7 Q. Now Doctor Stadel made his 8 statistical analysis based in part on statistics 9 supplied to him from Lilly, correct? 10 A. Can we be specific about one 11 term? You're using, I think, statistics and data 12 interchangeably and to speed things along a 13 little bit, let's be specific about them. So 14 could you rephrase that question accordingly? 15 Q. Wasn't the statistical 16 analysis done by Doctor Stadel at the FDA, an 17 analysis of some of the data that was supplied by 18 Lilly? 19 A. That's correct, sir. 20 Q. A large part of data in that 21 statistical analysis was supplied by Lilly, 22 wasn't it? 23 A. We've kind of questioned about 24 this word earlier. I mean there was a Page 145 1 significant amount from Lilly, but I think there 2 were also significant amounts from other sources, 3 their spontaneous adverse event reporting system, 4 for example. 5 Q. Doesn't Lilly have the best 6 record of any pharmaceutical company of Lilly 7 itself generating the 1639 data to the FDA? 8 A. It's my understanding we do, 9 yes. 10 Q. Isn't that what you're talking 11 about when you're talking about spontaneous 12 reporting? 13 A. That's the spontaneous system, 14 yes, sir. 15 Q. And so you're going to have 16 ninety-eight percent or in the nineties percent, 17 of the data of the spontaneous reports is 18 actually going to be generated by Lilly, isn't 19 it? 20 A. I wouldn't characterize 21 percentage, sir. A significant portion will come 22 from us, yes. 23 Q. What other data did Doctor 24 Stadel use in his statistical analysis that was Page 146 1 not supplied by Lilly? 2 A. It was my understanding -- we 3 already talked about spontaneous data? 4 Q. Yes. 5 A. We made that distinction. I 6 believe, and I think the record of the advisory 7 committee meeting will probably reflect this, but 8 I believe we also looked at the literature, 9 medical literature. 10 Q. In making a statistical 11 analysis? 12 A. Certainly, something called a 13 meta-analysis uses information such as that. 14 Q. Meta? 15 A. Meta, M-E-T-A, I'm sorry. 16 Q. Are you talking about Doctor 17 Beasley's work? 18 A. No, I'm talking about Stadel. 19 Q. Are you saying Doctor Stadel 20 looked at Doctor Beasley's meta-analysis in 21 making his statistical analysis done by the Food 22 and Drug Administration in this advisory 23 committee meeting of 1991? 24 A. I'm not sure what he looked Page 147 1 at. I know he looked at the literature. 2 Q. Then how do you know -- how 3 can you tell me then, that he used some other 4 analysis or looked at some medical literature, if 5 you don't know what he looked at? 6 MR. MYERS: Let me object to the form, 7 Paul, because you simply didn't listen to his 8 answer. He said he thought the record would bear 9 it out. He qualified and he said he thought he 10 knew where it came from. 11 A. And I think I can clarify it 12 further, too. I think your question was, would a 13 statistician use published clinical trial 14 information for a statistical analysis. 15 Q. Okay. 16 A. And I said yes, they might. 17 There is a process, a well-accepted worldwide 18 process called a meta-analysis approach. That's 19 like saying you use chi square or you use 20 students T test, it is a process. So I'm not 21 sure whether he did that or not. You challenged 22 me on whether published information would be 23 valid and that is my saying that yes, it is, the 24 statisticians utilized meta-analysis. And now Page 148 1 I've exhausted everything I know about 2 statistics. 3 Q. Which is much more than I 4 know, you can become exhausted on it a lot later 5 date then I can. Do you know for a fact that 6 Doctor Stadel employed looking at any 7 meta-analysis -- 8 A. No. 9 Q. -- for the statistical 10 analysis that he presented before the Food and 11 Drug Administration advisory committee in 12 September, 1991? 13 A. No, that kind of detail I 14 wouldn't know, but I'm sure it would be reflected 15 in the record. 16 Q. Well, we're working on it. Is 17 the testing done independently by the Food and 18 Drug Administration -- 19 A. Right. 20 Q. -- versus the testing done by 21 Eli Lilly and Company, and now we're 22 post-December, 1987 when the NDA was approved? 23 A. Post-approval, in other words, 24 yes, sir. Page 149 1 Q. And you -- what you've given 2 me is the statistical analysis done by the FDA. 3 Any other testing done? 4 A. Not that I'm aware that the 5 agency did. I don't know if this is supposed to 6 be on the record or not, but I'm -- I don't want 7 to interrupt your train of thought or anything. 8 (DISCUSSION OFF THE RECORD.) 9 MR. SMITH: Doctor Talbott, if you 10 will indulge us for a minute, we've got a matter 11 that we need to take up probably and put on the 12 record. Mister Myers advised me this morning 13 that he had been in contact with counsel from 14 Florida and Atlanta and that counsel representing 15 Lilly and counsel, possibly counsel -- 16 THE WITNESS: Should I leave? 17 MR. MYERS: You can tune out. 18 THE WITNESS: I'm sorry, I thought you 19 were directing this to me, Mister Smith, I'm 20 sorry. 21 MR. SMITH: And that counsel 22 representing Doctor Slater in Florida, had 23 advised him that there were problems with 24 transcription of Doctor Slater's depositions and Page 150 1 that there were several inaccuracies in the 2 transcription of the deposition testimony of 3 Doctor Slater. I was concerned about that and so 4 I made inquiry, or Miss Zettler made inquiry of 5 the court reporter who took that deposition who 6 is sitting here present in the room, and she 7 advised that Doctor Slater had, in 8 fact, signed his deposition, signed his errata 9 sheet with no changes and that it had been 10 returned to the court reporter over two weeks 11 ago. 12 MR. MYERS: You're telling me 13 something that I am hearing for the first time. 14 My purpose in raising it with you this morning, 15 Paul, was we had a brief discussion 16 about it last week, I guess it was on Friday, on 17 the subject of there being a request for more 18 time. I made a representation that I understood 19 that there were not any transcription problems 20 and in conversation with my partner, Mister Lore, 21 I was led to believe that, in fact, that was not 22 the case. And since I was not at the deposition 23 and didn't read the transcript, I was not aware 24 of that and simply brought that to your Page 151 1 attention. I'm not aware or I have not seen that 2 the transcript has been signed or not signed, I 3 just don't know that, I'm hearing that for the 4 first time. And, you know, if that's the case 5 then it's simply a matter of I will let Mister 6 Lore take that up with Mister Armstrong and 7 Doctor Slater, that's all I can say. I was 8 acting as a conduit of information. 9 MR. SMITH: I understand that. 10 MS. ZETTLER: It's our understanding 11 that the original deposition was transmitted to 12 the court reporter by Eli Lilly, number one, and 13 number two, a motion was made within the past 14 week or so by Lilly, local counsel for Lilly in 15 Louisville, to extend the time to which Doctor 16 Slater would have the opportunity to read that 17 transcript, because supposedly he had not gotten 18 through it and had not done so. 19 MR. SMITH: And the same motion was 20 made in Indiana. 21 MS. ZETTLER: Now we're hearing 22 something different. 23 MR. MYERS: I have seen two motions. 24 One, I think, that Mister Stopher filed and one Page 152 1 that was filed by Mister Armstrong, who 2 represents Doctor Slater. But as I say, I just 3 don't have any knowledge, as we sit here today, 4 about the matters that you have brought to my 5 attention and all I can say is I can look into 6 those matters. I really don't know what comment 7 to make beyond that. My purpose in having that 8 discussion with Mister Smith, was to simply 9 correct a misstatement that I had made on Friday 10 based on lack of information, you know. I really 11 don't know what other reply to make. 12 MR. SMITH: Well, we would like to put 13 on the record that if there is a movement afoot, 14 and if there is going to be some contention that 15 Doctor Slater's deposition was inaccurately 16 transcribed, then we want to know that 17 immediately and want to know immediately those 18 portions of the record that Lilly or Doctor 19 Slater is claiming are inaccurate. 20 MR. MYERS: Okay. I understand your 21 position and not having been there and not having 22 read the transcript, I will simply have to make 23 an inquiry of Mister Lore and of Mister Armstrong 24 and get a reply to that. Doctor Talbott, tune Page 153 1 back in. 2 THE WITNESS: Okay, thank you. 3 Q. (BY MR. SMITH) So we will be 4 clear, Doctor Talbott, the Food and Drug 5 Administration did not conduct any clinical 6 trials on human beings concerning Prozac, did 7 they? 8 A. That's correct. 9 Q. The Food and Drug 10 Administration didn't conduct any clinical trials 11 or trials of any nature on animals? 12 A. Not to my understanding, they 13 didn't, sir, no. 14 Q. All information that the Food 15 and Drug Administration -- that the Food and Drug 16 Administration has, as far as you know, 17 concerning the clinical trials on humans, was 18 supplied to the Food and Drug Administration by 19 Eli Lilly and Company. 20 A. That's not correct. 21 Q. All right. Were there 22 clinical trials on Prozac done by individuals or 23 entities other than Eli Lilly and Company? 24 A. I'm sure there have been in Page 154 1 the literature publications about trials that 2 were conducted by individual investigators, not 3 under a Lilly IND and at their own impact. And 4 we said earlier, in the September '91 advisory 5 committee meeting, it was my recollection that 6 Doctor Stadel mentioned that he had looked at 7 published reports in addition to the clinical 8 trial reports that Lilly had supplied to them. 9 So that's the reason for my answer being what it 10 was. 11 Q. Well, is it your testimony 12 that there were entities other than Eli Lilly 13 that conducted clinical trials on Prozac, on 14 humans? 15 A. Yes. 16 Q. Would they have had to obtain 17 the Prozac that they used for those clinical 18 trials from Eli Lilly and Company? 19 A. They could have bought it on 20 the open market and used it in their trials. So 21 since we were the only supplier of it, you could 22 say that we were the origin of that material, but 23 we did not give it to them perhaps. 24 Q. Let's back up a little bit. Page 155 1 All the clinical trials that were done on Prozac, 2 Fluoxetine Hydrochloride, prior to it being 3 approved by the Food and Drug Administration in 4 December of 1987, would have had to have been 5 done by Eli Lilly and Company? 6 A. That's correct, sir. 7 Q. No other company or no other 8 individual, other than somebody hired by Lilly to 9 do it, could have done a clinical trial on Prozac 10 prior to its being marketed in December of 1987? 11 A. That's my understanding, sir, 12 yes. 13 Q. Because it was an 14 investigational compound, correct? 15 A. Correct, under an IND, that's 16 right, sir. 17 Q. After the Food and Drug 18 Administration approved Prozac for use in human 19 beings, are you saying that some independent 20 company or individual or investigator has done 21 clinical trials on Prozac? 22 A. I don't know, I can't sight 23 you a specific individual or company, but I do 24 know that there are reports always in the Page 156 1 literature about all new drugs that individual 2 investigators have, for example, obtained the 3 drug in the normal market place and have 4 conducted their own individual trials. So I was 5 trying to be as complete in answering your 6 question as I possibly could be. 7 Q. Well, would those clinical 8 trials have been submitted to the Food and Drug 9 Administration? 10 MR. MYERS: By? 11 MR. SMITH: By the investigator. 12 A. I really don't know, sir. It 13 all depends on the conditions under which they 14 conducted them. 15 Q. Would those clinical trials 16 have been supplied to the Food and Drug 17 Administration by Lilly? 18 A. If we had been made aware of 19 it, yes. 20 Q. Well, do you think there may 21 be some clinical trials that had been done on 22 Prozac since December of 1987 that Lilly is not 23 aware of? 24 A. I can't think of any, sir. Page 157 1 Q. Who would have the most 2 knowledge concerning clinical trials that might 3 have been conducted by other individuals or 4 entities on Prozac since approval in December, 5 1987? 6 A. Probably one of my physician 7 colleagues, Doctor Tollefson, for example. 8 Q. Anybody else? 9 A. I think he probably would be 10 the one most knowledgable. 11 Q. Lilly has continued to do 12 clinical trials on Prozac since it's been 13 approved for depression, haven't they? 14 A. That's correct, sir. 15 Q. And have they done any 16 clinical trials on Prozac for depression -- 17 depressive indications? You follow what I am 18 saying, for treatment of depression as opposed to 19 obsessive-compulsive disorder, weight disorder or 20 some other indication. 21 A. I really don't know, sir, 22 Doctor Tollefson probably could answer that 23 better than I could. 24 Q. Well, if Lilly had done that, Page 158 1 those clinical trials, the results of those 2 clinical trials would have been submitted to the 3 Food and Drug Administration, wouldn't they? 4 A. Yes. 5 Q. And they would have been 6 submitted by you as director of medical 7 regulatory affairs? 8 A. That's correct, sir. The 9 application then should reflect what we have 10 submitted. 11 Q. But you don't have any 12 independent recollection of submitting clinical 13 trial data to the Food and Drug Administration? 14 A. Well, I think the original 15 question was about additional depressive trials 16 and so I'm inferring, and perhaps I should just 17 ask you to clarify clinical trial data about? 18 Q. Depression. 19 A. Not specifically about that, 20 no. 21 Q. Other indications? 22 A. Yes. 23 Q. Which would be? 24 A. Again, we are talking about Page 159 1 Prozac? 2 Q. Yes. 3 A. It will be for 4 obsessive-compulsive disorder, for bulimia and 5 for obesity. 6 Q. Now are you aware of any other 7 investigator who has done clinical trials on 8 using Prozac for these other uses since December, 9 1987? 10 A. For the three uses I just 11 mentioned? 12 Q. Yes. 13 A. I am sure there were a number 14 of investigators that conducted, I mean I can't 15 name an individual investigator, but there were 16 clinical trials conducted by investigators for 17 those indications. 18 Q. I understand that, but those 19 were all done -- I assume those were done by 20 investigators hired by Lilly pursuant to Lilly 21 protocol, weren't they? 22 A. It's my understanding, yes. 23 Q. My question is, have there 24 been any clinical trials by somebody else that Page 160 1 used some other protocol that you're not aware 2 of, or that it is outside of Lilly? 3 A. No, I'm not aware of any, sir. 4 Q. Would there be any prohibition 5 against some outside investigator doing a 6 clinical trial on Prozac, at this time? 7 MR. MYERS: Let me just object to the 8 form. When you say prohibition, you mean a legal 9 prohibition or some sort of patent or trademark 10 thing? 11 MR. SMITH: Some sort of -- 12 Q. Would there be any way that 13 Lilly, as far as you know, and I'm not holding 14 you to a legal opinion, I'm just asking you for 15 your opinion as director of medical regulatory 16 affairs, would there be any way that Lilly could 17 prevent an independent investigator from doing an 18 independent clinical trial using Prozac? 19 A. I'm not sure that I've ever -- 20 give me just a second, I'm not sure I've ever 21 been asked that question before or even thought 22 about it. I'm not sure that we, Lilly could 23 prevent that, no. 24 Q. But you have not been made Page 161 1 aware of anybody -- 2 A. No, no. 3 MR. MYERS: Let him finish. 4 A. I'm sorry, Mister Smith. 5 Q. You have not been made aware 6 of anybody that's doing that? 7 A. No, sir, I haven't. 8 Q. I think we covered that there 9 had not been any clinical human trials on 10 Fluoxetine or Prozac done prior to December 1987 11 to test whether or not there is a relationship 12 between Prozac and suicidality, correct? 13 A. Not for that specifically, no. 14 Q. Since 1987, has Lilly run any 15 clinical trials on humans to determine whether or 16 not Prozac causes suicidality in humans? 17 A. Specifically, I am not aware 18 of any, sir, no. 19 Q. Are you aware of any generally 20 that has examined that issue as part of maybe a 21 number of issues that are being analyzed? 22 A. I think that any adverse event 23 would be tracked as a result of a clinical trial, 24 that's just normal practice. So in a general Page 162 1 sense, the answer would be yes to your question. 2 Specifically, a trial conducted for suicide, no. 3 Q. And what I'm talking about is 4 something that would be done under a protocol -- 5 A. Uh-huh. 6 Q. -- that would call for an 7 examination of particular issues, one, suicide, 8 two, weight loss, three, obsessive compulsive 9 disorder, combining -- or factors thereof? 10 A. I'm not -- 11 Q. Do you follow what I'm saying? 12 MR. MYERS: That measures as an 13 objective of the study? 14 MR. SMITH: Yes. 15 A. Could you -- I'm not sure I 16 understand that, because there were three things 17 there. 18 Q. Since December 1987, are you 19 aware of any clinical trials that have been done 20 by Lilly that have a protocol that has as any 21 part an objective or a component of a reason to 22 do the investigation to examine the question as 23 to whether or not Prozac causes suicidal ideation 24 in humans? Page 163 1 A. Specifically, no. 2 Q. Generally? 3 A. Again, adverse events as part 4 of any clinical trial. 5 Q. And when you say adverse 6 events, you're talking about, well, if there were 7 reported suicidal ideation or suicide attempts as 8 an adverse event in connection with that clinical 9 trial, then we would know that by virtue of it 10 being reported by the investigator? 11 A. That's correct, sir. 12 Q. But that would only be 13 incidental to the purpose of the clinical trial? 14 A. Looking for that specific 15 adverse event or any specific adverse event, per 16 se, would be incidental and not specific to it. 17 Q. Specific to that particular 18 trial? 19 A. The objective of that trial, 20 yes. 21 Q. Why has Lilly not done any 22 clinical trials to determine whether or not 23 Prozac causes suicidal ideation in humans? 24 MR. MYERS: Before he answers, let me Page 164 1 object to the form only to the extent it may call 2 upon him to venture into clinical and medical 3 areas. To that extent, I object to the form. 4 But if you know in your own capacity, Doctor, 5 tell Mister Smith. 6 A. I don't know in my capacity as 7 director of medical regulatory affairs or 8 worldwide regulatory affairs. 9 Q. Have you ever seen any 10 suggestion that Lilly conduct a clinical trial in 11 humans to determine whether or not Prozac causes 12 suicidality in humans? 13 MR. MYERS: Let me object to the form 14 and the term "any suggestion" as being awfully 15 vague and undefined. 16 Q. Any suggestion by Lilly 17 employees that such a study be done. 18 A. Well, I think earlier we 19 talked about some potential protocols that 20 followed up to one of these meetings that we 21 talked about this morning that were shared with 22 FDA by Doctor Zerbe. So, I don't know if that 23 speaks to your question or not. I've seen that 24 aspect of it. Page 165 1 (PLAINTIFFS' EXHIBIT 3 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. Would you review Exhibit 3 for 5 me, Doctor Talbott? 6 A. All right, sir. 7 Q. That appears to be an E-Mail 8 correspondence in-house within Lilly a few months 9 after this October 1990 and November 1990 10 exhibits that we have been discussing, correct? 11 A. Yes, sir, it's a February 12 13th, 1991, E-Mail message or computer message 13 from Doctor Leigh Thompson to perhaps two dozen 14 individuals, perhaps even more than that. 15 Q. Did you discuss this memo with 16 Doctor Thompson? 17 A. I don't recall it sir, no. 18 I'm sorry, in answer to your question, I don't 19 recall discussing it with Doctor Thompson. 20 Q. You received a copy of the 21 memo? 22 A. Yes, I did. 23 Q. And do you specifically recall 24 getting this memo? Page 166 1 A. No, I don't. 2 Q. This is part of the documents 3 though that you reviewed a couple of times in the 4 last few months in the preparation of your 5 deposition, is it not? 6 A. I don't recall it as being 7 part of that, no. This one doesn't ring a bell. 8 Q. Well, it was supplied to us -- 9 A. Okay. That -- what I just 10 said doesn't mean that it wasn't in there, I just 11 don't recall it. 12 Q. There Doctor Thompson is 13 talking about Prozac and suicidality, isn't he? 14 A. Yes, sir. 15 Q. And he says, primarily for the 16 FDA, but also to nail down that Prozac reduces 17 the risk of suicidality, we will probably do two 18 studies. Correct, that's what is says, doesn't 19 it? 20 A. Let me, if I may, just to read 21 all this, it's very short. To let you know where 22 we are in depression, let me give you a brief 23 note, primarily for the FDA, but also to nail 24 down that Prozac reduces, in capital letters, the Page 167 1 risk of suicidality, we will probably do two 2 studies, colon. 3 Q. All right. My question is, do 4 you recall any discussion between Lilly employees 5 and the Food and Drug Administration, anything 6 about doing these two studies? 7 A. Again, because I don't have 8 any professional clinical background, I don't 9 know if these proposals by Doctor Thompson were 10 what Doctor Zerbe was talking about in the 11 mentions that I made this morning. But I do know 12 that he got in contact with the FDA about some 13 potential studies and about talking about 14 designs, et cetera. So, I don't know if this was 15 the subject of those memoranda and those 16 telephone calls or not, but it could be. I don't 17 specifically know though that this was talked 18 with the FDA. I know that I didn't, certainly. 19 Q. The memo says that primarily 20 for the the FDA we will probably do two studies, 21 doesn't it? 22 A. Uh-huh. 23 Q. Is that a yes? 24 A. I'm sorry. Yes, it does, sir. Page 168 1 Q. And this follows up, I assume, 2 with your memo, which is Exhibit 2 of October 3 10th, where they were talking about a rechallenge 4 study and a large prospective randomized study, 5 correct? 6 A. Well, to put that in context, 7 from my September 25th meeting memo dated October 8 10th, it was about a September 25th meeting, that 9 specifically says the limitations of small 10 enrichment rechallenge studies, as well as large 11 prospective randomized studies, were reviewed by 12 all participants. 13 Q. You don't agree with me that 14 this ties in with your memo of October 10th? 15 A. Well, again, I'm not a 16 clinician, so I don't know if these -- either of 17 these is, small enrichment rechallenge or large 18 prospective randomized study, I could go through 19 again and read if you want me to. 20 Q. Whatever. Let's talk about 21 Exhibit 3. 22 A. All right. 23 Q. If you were doing a study for 24 the FDA, or if you were doing a clinical trial of Page 169 1 any sort in February of 1991, would you have to -- 2 would Lilly have had to have submitted a protocol 3 to the Food and Drug Administration for such 4 study? 5 MR. MYERS: When you say if they were 6 doing it, that is carrying it out at that point 7 in time? You said doing a clinical study in 8 whatever the date was. 9 Q. Okay, excuse me. If you were 10 going to do a study in February of 1991, to do 11 that study would the FDA require that Lilly 12 submit to them a protocol of the study in order 13 to do the study? 14 A. I believe that would fall 15 under the IND requirements, yes. 16 Q. And would that protocol have 17 to be approved by the Food and Drug 18 Administration? 19 A. Yes, sir. 20 Q. Even though, by February of 21 1991, Prozac is already approved -- an approved 22 drug? 23 A. That's correct, sir. 24 Q. And even though anybody could Page 170 1 do a study, if they wanted to, correct? 2 A. Well, any individual physician 3 could obtain the drug and do that. 4 Q. As long they could prescribe 5 the drug? 6 A. Yes, exactly, that's what I 7 was getting ready to say. 8 Q. But if the manufacturer of the 9 drug, Eli Lilly and Company, in February of 1991, 10 wanted to do a clinical trial, they would need to 11 submit a protocol and that protocol would have to 12 be approved by the Food and Drug Administration? 13 A. That would be my advice to the 14 company on this, yes, sir, from my understanding. 15 Q. And that's because federal 16 regulations require that as per your 17 interpretation? 18 A. I think specifically, yes, 19 parts of 312, 21 CFR 312. 20 Q. Doctor Thompson mentions in 21 the memo, number one, a challenge study, blinded 22 prospective, in any patient we identify who has 23 the intense suicidal ideation similar to that 24 described by Teicher, the NEJM -- and I assume Page 171 1 that means the New England Journal of Medicine? 2 A. I think so too, Mister Smith, 3 yes. 4 Q. Letter last week, and the 5 upcoming publication by -- and then that word is 6 marked out, correct? 7 A. That's correct, sir, the last 8 word in the sentence, it appears. 9 Q. Is that what is known as a -- 10 at least from your interpretation as a regulatory 11 scientist and the director of medical regulatory 12 affairs, would that study mentioned there as one 13 be what is known as a rechallenge study? Even 14 though he uses the term challenge, would 15 rechallenge be interchangeable there? 16 A. I really don't know. Leigh's 17 very specific on his speech and I would think he 18 would probably mean -- if he said challenge, he 19 means challenge, if he wanted to say rechallenge, 20 he would say rechallenge. 21 Q. Your experience with Mister 22 Thompson or Doctor Thompson -- 23 A. It is Doctor Thompson, sir. 24 Q. And I apologize to him, in Page 172 1 absentia. 2 A. I will tell him that. 3 MS ZETTLER: You can apologize in 4 person in a few weeks, Paul. 5 Q. Your experience with Doctor 6 Thompson has been that he is very specific in his 7 speech? 8 A. At least in circumstances such 9 as this, I think if he meant to say rechallenge, 10 he would have said it. 11 Q. If he was going to write a 12 memo, an E-Mail memo such as this, he generally 13 chooses his words carefully? 14 A. I think that when he's talking 15 about clinical terms, he's very specific. 16 Q. All right. And is he 17 generally specific in his ability to quote other 18 individuals? 19 A. Can you give me a 20 circumstance, a for instance? 21 Q. Do you know of any instances 22 where he's inaccurately quoted anybody? 23 A. Not that I'm aware of, sir, 24 no. Page 173 1 Q. Are you aware of instances 2 when his quotations and his explanations of what 3 other individuals have said has been proved to be 4 in fact accurate? 5 A. Accurate, yes, sir, I have. 6 Q. All right. So you don't know 7 for sure exactly what Doctor Thompson is meaning 8 here, other than he usually means what he says 9 when he says a challenge study? 10 A. When we talk about clinical 11 terms he is very specific, yes. 12 Q. And he goes on to describe 13 what that would involve, at least briefly. He 14 says that in any patient we identify with the 15 intense suicidal ideation -- that would be the 16 subjects of that study? 17 A. Give me a second, sir. That 18 appears to be the patient population he's 19 targeting, yes, sir. 20 Q. Then he goes on and he says 21 intake would be from spontaneous ADE reports, 22 right? 23 A. Let's see, we skip down to the 24 next sentence afterward, intake would be from Page 174 1 spontaneous ADE reports, that's correct. 2 Q. And when he says ADE, he means 3 adverse drug experience? 4 A. That's correct, sir. 5 Q. I assume he means individuals 6 who reported suicidal ideation? 7 A. I'm sorry? 8 Q. I assume he means individuals 9 who reported suicidal ideation. 10 A. Well, let's see, the patient 11 population, going back to his first sentence, in 12 any patient we identify who has -- I'm missing a 13 couple of letters, but it looks like the intense 14 suicidal ideation. 15 Q. Okay. So you would expect, as 16 the chief regulatory -- or the head of regulatory 17 affairs, that when he talks about spontaneous ADE 18 reports, he's talking about ADE reports that 19 report suicidal ideation? 20 A. That would be the inference 21 that I draw, yes. 22 Q. And he would get these ADE 23 reports from all depressive studies worldwide? 24 A. Let's see, again, Mister Page 175 1 Smith, intake -- again I'm missing some letters, 2 but I think it's intake would be from spontaneous 3 ADE reports from all, capitals, depression 4 studies worldwide and, looks like, from 5 prospective studies. So that would be from 6 studies from ADE reports and then from all 7 prospective studies. 8 Q. Then he said patients would 9 have to be treated by a competent investigator 10 for probably four or three months with Prozac 11 versus an alternative, correct? 12 A. Patients would have to be 13 treated by a competent investigator, probably for 14 three months with Prozac versus an alternative, 15 that's correct, sir. 16 Q. So what he's going to do, he's 17 going to take, as he suggests here, individuals 18 who had a bad experience or at least who have 19 reported as an adverse experience, suicidal 20 ideation and readminister the medication, 21 readministered -- and administer a comparitor 22 drug -- I guess when he says versus an 23 alternative, he's talking about a comparitor 24 drug. Page 176 1 A. I would think that's what he's 2 saying, yes. 3 Q. And examine the results of 4 that on a blinded basis, where the investigator 5 didn't know which drug the patients were taking? 6 A. Right. In the first sentence 7 he said a blinded prospective, that's what that 8 would indicate. Now, let's be sure, because when 9 we talked about an alternative, it wasn't Prozac 10 and an alternative. As I understand it here, it 11 would be Prozac or an alternative. I think when 12 you said it to me, you may have misstated it and 13 said Prozac and an alternative. My understanding 14 of what he's saying here just looking at this 15 would be that he wouldn't propose giving a 16 patient both drugs. 17 Q. Correct. What he would do is 18 he would take a patient that had had a bad 19 experience, that is suicidal ideation, with 20 Prozac, right? 21 MR. MYERS: Let me object to the form. 22 The memo at least does not say that, so is that 23 your interpretation? Are you asking if that's 24 what it says? Page 177 1 MR. SMITH: I don't know of anybody 2 that would describe suicidal ideation as anything 3 other than a bad experience. 4 MR. MYERS: No. You misunderstand my 5 objection. My objection is you're assuming that 6 the patient who had the suicidal ideation got 7 Prozac as opposed to some other drug or a 8 placebo, that's the assumption I think you're 9 making. 10 MS ZETTLER: I don't think you let him 11 finish with his question, I think he was getting 12 to it. 13 Q. (BY MR. SMITH) Well, the 14 patients that were described by Teicher were 15 individuals that were taking Prozac, isn't it? 16 A. Is that to me? 17 Q. Yes. 18 A. That was my understanding, 19 yes. 20 Q. The New England Journal of 21 Medicine article was concerning Prozac, patients 22 taking Prozac, wasn't it? 23 A. That one I don't recall, I'm 24 not familiar with. Page 178 1 Q. Intake would be from 2 spontaneous ADE reports, correct? 3 A. That's what it says here, yes. 4 Q. He's talking about Prozac 5 spontaneous ADE reports, isn't he? 6 A. That's true. We come in on 7 the basis of our use of Prozac, monitoring 8 Prozac. 9 Q. And he's talking about from 10 all depression studies worldwide, he's talking 11 about Prozac depression studies, isn't he? 12 A. Well, now we do -- we did, I 13 think, use some comparitors there so there is the 14 potential for a patient on a comparitor drug to 15 have had suicidal ideation. 16 Q. All right. But the intent was 17 to monitor people who had had a bad experience 18 with Prozac, wasn't it? 19 MR. MYERS: I object to the form, on 20 the same basis. 21 Q. In Prozac studies at least. 22 A. Well, again, it could be. And 23 again, he did not say intense suicidal ideation 24 with Prozac. He did refer to the Teicher Page 179 1 article, I agree with that. I've already said I 2 don't know -- I don't recall what the NEJM letter 3 was. Spontaneous ADE reports on Prozac would 4 probably be pretty much on Prozac. But all 5 depression studies worldwide, and then the next 6 line too, we didn't get into it, but from 7 prospective studies, those could have comparitor 8 drugs that aren't Prozac. 9 Q. But all of the studies would 10 have Prozac as the primary drug being 11 investigated, wouldn't they? 12 A. That's correct, sir, yes. 13 Q. It says details are being 14 worked out on this, correct? 15 A. Just a minute, Mister Smith, I 16 lost my place. 17 Q. Last sentence. 18 A. Last sentence, yes, details 19 are being worked out, that's item number one. 20 Q. The point of this study would 21 be, as you understand it as director of medical 22 regulatory affairs for Lilly, would be to 23 determine whether or not that bad experience 24 could be reproduced -- that adverse experience, Page 180 1 could be reproduced by reintroduction of the 2 investigational drug. 3 MR. MYERS: Let me object to the form 4 of the question. I don't think that's what it 5 says. But if you know, tell him, Doctor. 6 A. Well, a challenge study is 7 generally a study that is given to evoke a 8 particular adverse event. 9 Q. Okay. 10 A. So I think that's how I would 11 answer your question. 12 Q. Which is basically my 13 question, correct? 14 A. I'm sorry? 15 Q. The object is to see the 16 individuals reacting in similar or different 17 manner than they had reacted to the drug 18 previously? 19 A. That's right, that's a good 20 definition of a challenge study. 21 Q. Was that study done? 22 A. I don't know, sir, I don't 23 think so. 24 Q. Did you ever see a protocol Page 181 1 drafted by Lilly concerning the design of a study 2 like that? 3 A. That particular one, I don't 4 recall seeing one, sir. 5 Q. Have you ever seen anything 6 approved by the Food and Drug Administration 7 concerning this type of study? 8 MR. MYERS: Anything, being a 9 protocol? 10 MR. SMITH: Yes. 11 A. May I clarify? 12 Q. Uh-huh. 13 A. For Prozac? 14 Q. Yes. 15 A. No, not for Prozac. 16 Q. For any drugs? 17 A. I've seen instances where the 18 agency -- I think there was one anti-asthma drug 19 six or seven years ago where there were some 20 questions and the agency approved a rechallenge 21 study. Not for us, it was just in the general 22 literature. So specifically for Prozac, no. For 23 any drug, in answer to your follow-up question, 24 yes. Page 182 1 Q. In a situation where they were 2 checking on the anti-asthma drug -- 3 A. Yes, sir. 4 Q. -- what's your understanding 5 of the value of that challenge study, why is that 6 something that would be of value? Based on your 7 knowledge as a fellow with a Ph.D and as the 8 director of regulatory affairs at Eli Lilly and 9 Company. 10 A. I think what I would go back 11 to was the definition used just a few minutes 12 ago, the challenge study, and that was to see if 13 the administration of a drug would evoke a 14 particular adverse event. 15 Q. Would that be of scientific 16 interest? 17 A. Yes. 18 Q. But as far as you know, a 19 study such as that has never been done by Lilly 20 on Prozac? 21 A. No, sir, I don't. I don't 22 know that that study has been done. 23 Q. Wouldn't you know had there 24 been one? Page 183 1 A. I would think so, yes, sir. 2 Q. Do you know of anybody else 3 that would have more knowledge concerning 4 clinical trials being done, that were done in 5 part, or at least it says by Doctor Thompson 6 primarily for the FDA? 7 A. Well, go back to Doctor 8 Tollefson, I think, when it came to this 9 particular area. I think Doctor Tollefson -- I 10 may have misspoken, earlier. Doctor Tollefson 11 would know, I think, more about clinical trials 12 with CNS drugs to include Prozac than I do. 13 Q. But to get FDA permission, 14 which would have had to have been received, he'd 15 have to go through you, wouldn't he? 16 A. He would submit it out of my 17 office, that's correct, sir. 18 Q. And you would know what was 19 submitted out of your office, wouldn't you? 20 A. I would know, but I might not 21 recall, if that's what you're leading to. 22 Q. You would recall something 23 like this, wouldn't you? 24 A. I think the files would speak Page 184 1 for themselves. If we submitted it, it's in the 2 NDA application file, which I know you have. So 3 that's the best answer I can give you. 4 Q. Has any such challenge study 5 been submitted to any regulatory body but 6 rejected by the regulatory body? 7 A. Not that I'm aware of, sir. 8 Q. Do you know of any regulatory 9 reason why a challenge study such as is suggested 10 by Doctor Leigh Thompson in February 1991, could 11 not be done? 12 A. Regulatory reason alone? 13 Q. Yes. 14 A. No, I don't think there would 15 be any regulations that I'm aware of that would 16 prohibit it. 17 Q. I'm going to continue, but you 18 stop me when you need to stop. 19 A. Would you mind now, is this a 20 good time for you? 21 Q. Sure. 22 (A SHORT RECESS WAS TAKEN.) 23 Q. (BY MR. SMITH) Do you know of 24 any reason why such a study couldn't be done? Page 185 1 A. None that really comes to 2 mind, no. 3 Q. The second study that Doctor 4 Thompson mentions in connection with his February 5 13th memo is, and I will quote him, a prospective 6 study using new instruments to measure 7 suicidality in depressed folks randomly given 8 Prozac versus placebo or active comparitor, 9 correct? 10 A. Just a second. Is it okay if 11 I undo them because it's over some words up 12 there? Maybe if I -- could I just bend it around 13 for a second, maybe I can see it. 14 Q. Yes. 15 A. Depressed folks randomly given 16 Prozac versus placebo or active comparitor. Yes, 17 that's correct, sir. 18 Q. Were you aware in February, 19 1991, that there were new instruments to measure 20 suicidality in depressed folks? 21 MR. MYERS: I object to the form only 22 to the extent it assumes that there were. 23 MR. HARRIS: Also, we will join in the 24 objection in that it calls for this witness to Page 186 1 testify about medical he is not competent to 2 testify about, therefore it requires speculation 3 on his part. 4 MR. MYERS: Subject to that, Doctor, 5 if you know, tell Mister Smith. 6 A. I don't know, Mister Smith. 7 Q. Well, did you know what 8 measurements were used during the clinical trials 9 prior to approval by the Food and Drug 10 Administration to measure suicidality? 11 A. No, I don't, sir. 12 Q. Have you seen any articles or 13 scientific publications that mentioned new 14 measurements to measure suicidality, at any time? 15 A. I don't recall any, sir. 16 Q. Do you know whether or not a 17 prospective study using new instruments to 18 measure suicidality in depressed folks randomly 19 given Prozac versus placebo or active comparitor 20 was ever done? 21 A. No, sir, I don't know. 22 Q. Again, if Lilly had done that, 23 would they have had to have done that under a 24 protocol? Page 187 1 A. Yes. 2 Q. And would that protocol have 3 had to have been submitted to the Food and Drug 4 Administration? 5 A. I believe we have talked -- 6 I'm sorry, yes. 7 Q. And would that request for 8 approval of that protocol have had to come via 9 your signature as the director of medical 10 regulatory affairs? 11 A. It would have gone through my 12 office, that's correct, sir. 13 Q. And you're not aware of any 14 such request? 15 A. I don't recall any at all, 16 sir. 17 Q. You have never seen any 18 protocol for a prospective study using new 19 instruments to measure suicidality, as far as you 20 know? 21 A. Again, I know that there was 22 some discussion between Doctor Zerbe and people 23 at FDA about potential studies. 24 Q. I understand that. Page 188 1 A. And whether I saw a protocol 2 or not as part of those discussions, I don't 3 recall. So, I can't say yes or no, I just don't 4 recall any. 5 Q. You don't know of any studies 6 that came to fruition? 7 A. No, sir. I think I've 8 answered that before. But no, I don't. 9 Q. And you don't know of any 10 protocols that were approved -- 11 A. Not that I'm aware of. 12 Q. -- by the Food and Drug 13 Administration? 14 A. No. 15 Q. And you're not sure, but you 16 don't think you know of any protocols that were 17 submitted by Lilly to the Food and Drug 18 Administration concerning that? 19 A. I just don't recall if there 20 were any. 21 Q. The third type of study that 22 Doctor Thompson mentions is probably used 23 Fluoxetine as an active comparitor in many of the 24 studies of new anti-depressants. It says, this Page 189 1 would then serve as an additional suicidality 2 studies for the FDA. Correct? 3 A. That's what it says there, 4 yes, sir. 5 Q. Do you know whether or not 6 Lilly used Fluoxetine as an active comparitor in 7 a study of a new antidepressant? And again, I'll 8 caution you, Doctor Talbott, to not reveal the 9 names of any other potential medicines being 10 promulgated by Lilly. 11 A. Okay, thank you. I can't 12 specifically recall any, sir. 13 Q. Again, especially if Lilly 14 were studying the new antidepressant, and if 15 Fluoxetine was going to be used as the active 16 comparitor, that would be something where there 17 would have to be FDA approval for such a study, 18 is that correct? 19 A. That's correct, sir. 20 Q. And there would have to be a 21 formal protocol prepared by Lilly. 22 A. And submitted to the agency, 23 that's correct, sir. 24 Q. And you're aware of none? Page 190 1 A. Not that I recall, no, sir. 2 Q. That has been prepared or 3 submitted? 4 A. I don't recall any. 5 Q. Do you have any knowledge 6 concerning why such a study hasn't been done? 7 A. No, sir. 8 Q. Do you have any knowledge why 9 a prospective study using new instruments to 10 measure suicidality hasn't been done by Lilly? 11 A. No, sir. 12 Q. I think you said earlier this 13 morning that there were several studies that were 14 discussed -- among those you talked about Doctor 15 Zerbe's discussions. 16 A. That's correct, sir. 17 Q. And that after the FDA 18 advisory committee meeting in September of 1991 19 on suicidality, that there was a concensus that 20 there was no need for that type of study, is that 21 right, is that what you said? 22 A. That was my take of the 23 situation, that's correct. 24 Q. Is that still your take of the Page 191 1 situation? 2 A. Oh, yes, yes. 3 Q. It's just not necessary to do 4 these studies because of what was done at the 5 advisory committee meeting in October -- 6 September of 1991? 7 A. Not only what was done, but 8 what was discussed, the data review, the 9 conclusions reached by agency and the advisory 10 panel and ourselves. 11 Q. You, as the director of 12 medical regulatory affairs at that time for Eli 13 Lilly and Company, felt that that was sufficient 14 with respect to the issue of Prozac and 15 suicidality? 16 A. Yes, sir. 17 Q. Doctor Thompson mentions in 18 that second sentence of the third study on page 19 2, he said we probably want to use Fluoxetine in 20 studies without placebo controls and possibly 21 when there is also a tricyclic control. Do you 22 know why he would make that statement, Doctor 23 Talbott? 24 MR. MYERS: Let me object to the form Page 192 1 only because it may call for him to speculate as 2 to what Doctor Thompson meant and also to render 3 some sort of clinical judgment about the creation 4 of any such trial. But if you know, tell him. 5 A. I really don't know. There 6 was -- I'm sorry, that was the last sentence 7 there you are talking about? 8 Q. Yes. 9 A. No, I don't know, Mister 10 Smith. 11 Q. Do you know, as director of 12 medical regulatory affairs for Eli Lilly and 13 Company, whether or not the pivotal clinical 14 trials that were submitted by Lilly for approval 15 of Prozac as an anti-depressant, were all trials 16 that involved placebo controls? 17 A. In other words -- may I see 18 what my understanding of the question is? 19 Q. Sure. 20 A. In other words, did all of the 21 pivotal trials have at least a placebo arm. 22 Q. Yes. 23 A. I believe that that is the 24 case. Now the NDA would reflect that, and either Page 193 1 confirm or reject, but I think the placebo arms 2 were included in each. 3 Q. Isn't it your understanding 4 that in order for a trial to be a pivotal trial, 5 it must include a placebo arm? 6 A. For the Food and Drug 7 Administration? 8 Q. Yes. 9 A. Yes, that's correct, sir. 10 Q. And do you recall -- and you 11 may have given this to us earlier, I think you 12 probably did, but I have forgotten. What is the 13 definition of a pivotal trial? 14 A. I don't think we talked about 15 that before. 16 Q. Why don't you give us your 17 definition as director of medical regulatory 18 affairs. 19 A. And it's not an official 20 agency position, because I don't think the agency 21 even uses those terms, per se. But these would 22 be well-controlled clinical trials that were 23 blinded, prospectively designed that included a 24 placebo and potentially an active arm or arms Page 194 1 against which your new drug was tested. And the 2 safety and efficacy data from these trials, these 3 pivotal trials, then would be used by the agency 4 to determine whether the drug was safe and 5 effective or not. 6 Q. But is it your understanding 7 that in order for it to be a pivotal trial, that 8 trial must have a placebo arm? 9 A. I think that is generally the 10 case, I think that is generally the case. I 11 wouldn't tell you, Mister Smith, that that is a 12 mandatory hard and fast rule from the agency all 13 the time, because I don't believe it's in the 14 regulations that way. 15 Q. So if Lilly were to do this 16 third item that Doctor Thompson suggests, that is 17 do a trial of Fluoxetine without placebo 18 controls, then this would never be a trial that 19 could be used by Lilly to support anything with 20 respect to -- any scientific determination with 21 respect to a pivotal trial, because it doesn't 22 have a placebo arm? 23 MR. MYERS: Let me object to the form 24 of the question. Go ahead and answer. Page 195 1 A. This is after approval, and 2 pivotal trials usually are directed toward 3 initial approval. 4 Q. I understand that. 5 A. So, I don't -- I'm sorry, 6 that's just a comment, I'm not even sure that's 7 even an answer. Maybe you could rephrase it. 8 Q. Hypothetically, if you are to 9 have submitted a trial such as is suggested by 10 Doctor Thompson to the Food and Drug 11 Administration for purposes of approval for the 12 drug, it could never serve as a pivotal trial 13 because that particular study didn't have a 14 placebo arm? 15 MR. MYERS: I object to the form, 16 again. Tell him if you know, Doctor Talbott. 17 A. I'm not sure -- let me answer 18 it this way. I don't think it could be a pivotal 19 study, because it really doesn't get at the 20 matter of efficacy. And pivotal studies to me 21 are those studies that are so constructed to 22 provide data on safety and efficacy. So I guess 23 I would agree with the fact that it couldn't be 24 submitted as a pivotal study, not so much because Page 196 1 it didn't have a placebo arm, per se, but rather 2 because it doesn't really get at safety and 3 efficacy. Doctor Thompson didn't mention 4 anything about efficacy, so to me a pivotal trial 5 always has safety and efficacy. 6 Q. All right. You're one of the 7 individuals to whom this memo was directed, 8 correct? 9 A. Let me go back here. Yes, I 10 am. 11 Q. Doctor Thompson, after making 12 these statements or thoughts or suggestions 13 concerning these three potential trials, raises 14 the question in the second paragraph of page 2, 15 after he talks about these trials he says, quote, 16 do these thoughts make any sense to you. 17 Correct? 18 A. Yes, sir, that's the second 19 paragraph, second page. 20 Q. I'm asking you now, Doctor 21 Talbott, do these thoughts make any sense to you? 22 MR. MYERS: Let me object to the form 23 of the question to the extent that question calls 24 upon the witness to make some sort of clinical Page 197 1 assessment of these proposals which he is not 2 qualified to make. 3 MS. ZETTLER: Thompson thought he was. 4 MR. MYERS: That's not what it says. 5 I object to the form. If you can answer Mister 6 Smith's question, do so. 7 A. I really wouldn't speak to the 8 clinical side of it. Maybe if you would bring it 9 over to an area -- 10 Q. How about medical -- do these 11 thoughts make any sense to you as director of 12 medical regulatory affairs for Lilly? 13 A. Well, from a regulatory point 14 of view, I don't see anything that would preclude 15 them. I think we talked about that all the way 16 through here. 17 Q. So is your answer to my 18 question that these thoughts do make sense to you 19 from a regulatory standpoint? 20 A. Let me answer it as a double 21 negative. It's certainly not nonsense. 22 Q. This next question is -- 23 Doctor Thompson's question is, suggestions, 24 correct? Page 198 1 A. Yes, sir. Just a one word 2 sentence there. 3 Q. Did you have any suggestions 4 to this memo? 5 A. I don't recall. 6 Q. Do you now? 7 A. No. 8 Q. His next sentence is, after I 9 get your input we'll start moving the group 10 forward to actually work on comprehensive plans 11 and protocols for these Prozac studies and the 12 first studies of S dash nor and mixed uptake, 13 period, Leigh. Correct? 14 A. Yes, with -- I've got a couple 15 of letters off here, but I think that's what it 16 adds up to. 17 Q. Do you know if there was ever 18 a group moving forward to actually work on 19 comprehensive plans and protocols? 20 A. I don't recall if there was 21 such a group, sir. 22 Q. Did you ever see any 23 comprehensive plan to input one of these studies? 24 A. Not to my recollection, no. Page 199 1 Q. Did you ever see any 2 comprehensive -- any protocol to implement one of 3 these studies? 4 A. I mentioned earlier about some 5 of the conversations Doctor Zerbe had with the 6 agency about protocols and I may have seen one as 7 a result of that, which could or could not be 8 part of this as well. So I can't conclusively 9 state that I've never, but I don't recall any. 10 (PLAINTIFFS' EXHIBIT 4 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. We have handed you a document 14 marked Exhibit 4, I believe. Would you read that 15 document for me, please, Doctor Talbott? 16 A. Sure, you want me to read it 17 to myself? 18 Q. Yes. Make yourself familiar 19 with it and I will probably end up reading it out 20 loud. 21 A. Okay, sir. 22 Q. Exhibit 4 is a memo dated May 23 15th, 1991, isn't it? 24 A. That's correct, sir. Page 200 1 Q. And that is a memo authored by 2 Doctor James Kotsanos, M.D.? 3 A. Kotsanos. That's correct, 4 sir. 5 Q. What was the date again? 6 A. May 15, 1991. 7 Q. May 15th. The memo is dated 8 about sixty days after this Exhibit 3 we've been 9 talking about, where Doctor Thompson is 10 suggesting some studies for the FDA, correct? 11 A. Did you say sixty? It would 12 be more like ninety, wouldn't it, February to 13 May? 14 Q. Yes, about ninety days. 15 A. Okay, yes. 16 Q. And apparently you all have by 17 this time had another meeting with employees of 18 the Food and Drug Administration, correct? 19 A. That's what this would 20 indicate, yes, sir. 21 Q. And it says at the FDA 22 meeting. I assume that was another one of the 23 meetings in Rockville, Maryland, home of the Food 24 and Drug Administration? Page 201 1 A. Most likely would be, yes, 2 sir. 3 Q. And you are an addressee on 4 that memo, are you not? 5 A. Right. 6 Q. You were present at the 7 meeting on May 13th, 1991, weren't you? 8 A. I don't recall, Mister Smith. 9 There may be some other records or indications 10 and I certainly don't recall that I wasn't there, 11 but I don't recall that I was there. 12 Q. Do you ever recall any 13 meetings that were held between Lilly employees 14 and members of the Food and Drug Administration, 15 where you, as director of medical regulatory 16 affairs, were not present? 17 A. Yes. 18 Q. What would be the occasion 19 when they wouldn't take the director of medical 20 regulatory affairs to a meeting with the Food and 21 Drug Administration? 22 A. There would be many times when 23 the regulatory scientist, in this case it would 24 be Doctor Webber, would represent regulatory. I Page 202 1 don't go to every meeting with the FDA. 2 Q. Doctor Webber said you did. 3 MR. MYERS: I object to the form, I 4 don't know that he did or he didn't. 5 A. Doctor Webber would be wrong 6 in that case. 7 MR. SMITH: The record will speak for 8 itself. 9 MR. MYERS: It will, I guess. 10 Q. He could be wrong, but you 11 disagree? 12 A. I disagree with it. I can 13 quote you chapter and verse very recently that I 14 haven't been there, not about Prozac if I may 15 add, too. 16 Q. I think he was talking about 17 Prozac, and I'm talking about Prozac. Do you 18 recall any Prozac meetings with Food and Drug 19 Administration that you were not present? 20 A. I didn't, for example, go to 21 the advisory committee meeting. 22 Q. Why? 23 A. I was back in Indianapolis, in 24 case there were any data that we had to Page 203 1 accumulate and send to the agency, so I was there 2 to head up that side of the operation. If a 3 question came up and our team did not have the 4 data right there then they were going to call 5 back and it would have been my job to work with 6 the physicians and the paramedicals, et cetera, 7 to get those data. So that's one case. 8 Q. So you had a team in 9 Washington -- 10 A. At the meeting itself. 11 Q. -- at the advisory committee 12 meeting. And then you had a separate team as 13 back up here in Indianapolis to supply them with 14 any data they needed? 15 A. I'm not sure I'd say back up, 16 it was a different role. Back up to me implies 17 that if something happens to this team the other 18 one goes in. This would be a support team. 19 Q. I was going to say maybe 20 support would be better. 21 A. Support is better, yes. 22 Q. And you all had the same 23 information that those Lilly employees in 24 Washington had, at that time? Page 204 1 A. Yes. 2 Q. And had access to greater 3 information? 4 A. Well, in the sense that a 5 computer was here in Indianapolis, yes. 6 Q. Do you recall any support that 7 you lent, specifically, at that meeting or for 8 that meeting in September of 1991? 9 A. During the day itself? No, I 10 don't. 11 Q. How about the day before or 12 the night before? 13 A. There may have been some 14 questions come in and we either faxed or looked 15 up some numbers and talked. I don't remember 16 giving any information myself, I may have helped 17 to triage some of those requests that came in. I 18 don't think I went to the computer and got any 19 information out myself. 20 Q. Well, do you recall physically 21 being present at the Lilly Corporate Headquarters 22 in Indianapolis that evening before, standing by 23 to lend support? 24 A. I think we worked maybe until -- Page 205 1 at least I stayed maybe until 5:30, 6:00, 6:30 or 2 so, not unduly late. 3 Q. Do you recall -- let's go back 4 to May 15th, of 1991. You said you didn't recall -- 5 A. No. 6 Q. -- whether you were at the 7 meeting or not, is that right? 8 A. That's correct, sir. 9 Q. But you don't recall 10 specifically that you weren't at the meeting 11 either? 12 A. No, just by the same token, 13 exactly. 14 Q. Can you tell by looking at the 15 individuals listed on page 1 of that exhibit, 16 that that's -- whether or not that's intended to 17 be a listing of individuals present at the 18 meeting? 19 A. I'm not sure that all these 20 folks would be there. I think that's what you're 21 asking, right? 22 Q. Yes. 23 A. Does this look like the sort 24 of group that would be there? I don't think so, Page 206 1 I don't think all of these folks would 2 necessarily be there. 3 Q. Do you have any idea who from 4 the Food and Drug Administration would be present 5 at the meeting? 6 A. Let me look again. When I 7 went through the first time, I looked to see if 8 there were any mentions of names of FDA'ers. 9 Give me just a second. Well, here, Mister Smith, 10 we can infer, item number 4, second page, there 11 is a reference to Doctor Stadel we've talked 12 about before, I believe I mentioned he was a 13 statistician. So, I think that it looks like 14 maybe he was involved and then there was a 15 mention there also of Doctor Leber, so maybe we 16 could say that he was involved as well. But I 17 don't see a list, like we had on my earlier memo 18 of -- what was that, September 25th, 1990, 19 meeting, there's not a block of FDA folks there. 20 Q. If you had been at this 21 meeting, would you have kept notes or would you 22 have done a memo? 23 A. I believe either that I or 24 Doctor Webber would have, yes. Page 207 1 Q. The subject of Exhibit 4, the 2 memo dated May 15th, 1991 -- 3 A. This is Exhibit 4 I'm looking 4 at right now? 5 Q. Yes. Is, quote, FDA meeting 6 to discuss Fluoxetine rechallenge protocol, 7 comma, May 13th, comma, 1991. 8 A. Yes, sir, that's the title. 9 Q. Now, do you know Doctor 10 Kotsanos? 11 A. Yes, I do. 12 Q. Is Doctor Kotsanos equally 13 adept at expressing himself in the written 14 language? 15 MR. MYERS: As? 16 MR. SMITH: As Doctor Leigh Thompson. 17 A. I don't think so. 18 Q. Why, do you think Leigh 19 Thompson is -- Doctor Leigh Thompson is the best 20 or -- 21 A. No, but I think that Leigh is 22 so precise on his clinical terminology, I don't 23 think I've ever seen a person that precise. 24 Q. But you don't have any reason Page 208 1 to disparage Doctor Kotsanos in his description 2 of the English language and what occurred? 3 A. I wouldn't disparage Doctor 4 Kotsanos at all about anything. 5 Q. I may be making too big a 6 point of it, Doctor Talbott. 7 A. Yes. 8 Q. Well, he uses the term 9 rechallenge and he speaks specifically of the 10 term protocol. 11 A. Uh-huh, I saw that. 12 Q. Which we, who have been taking 13 depositions and those of you that have been 14 giving depositions in these matters have almost 15 come to use those two terms, rechallenge and 16 protocol, to mean something pretty specific, 17 correct? 18 A. I'll agree to that, sure. 19 Q. Especially with respect to 20 protocol. Protocol is a formal -- or is a 21 written document that sets forth an outline for a 22 particular experimental study, especially 23 clinical trials, will set forth objectives, will 24 set forth guidelines for that, will set forth Page 209 1 duration, inclusion criteria, exclusion criteria, 2 dosage information and things of that nature, 3 right? 4 A. That's correct, I agree, 5 that's a good outline of protocol. 6 Q. Reasons for discontinuation, 7 things of that nature? 8 A. Yes. 9 Q. And these are the protocols 10 that we discussed earlier, that in the clinical 11 trial process must be submitted to the Food and 12 Drug Administration in a formal manner, correct? 13 A. Correct, sir. 14 Q. And must be approved by the 15 Food and Drug Administration in a formal manner? 16 A. The protocols? 17 Q. Yes. 18 A. Yes, sir. 19 Q. Now, by that -- with that 20 background, if you look at the caption of this 21 memo, it would appear to me that there was a 22 protocol either being drafted or being considered 23 at the time, is that right? Does that -- would 24 that be an accurate interpretation? Page 210 1 MR. MYERS: From the caption or the 2 rest of the memo? 3 MR. SMITH: From the caption. 4 A. Let's see, FDA meeting to 5 discuss Fluoxetine rechallenge protocol. 6 Q. If you just read the caption, 7 wouldn't you assume that there was some protocol 8 that was written that was being examined? 9 A. You might come to that 10 conclusion. I guess I could offer an alternative 11 and we might go, for example, hypothetical. 12 Because again, I can't recall whether I was was 13 at this meeting or not, but we might go there to 14 discuss developing a protocol. 15 Q. Okay. If you read the body of 16 the memo, it appears that your alternative 17 explanation might be correct, doesn't it? 18 A. Well, give me a second again, 19 I haven't looked at it within that context, bear 20 with me. In looking at this -- I'm sorry, I 21 don't know what the question is before me, Mister 22 Smith. I drifted, I was looking at this and I 23 forgot the question. Would you mind reading it 24 back? Page 211 1 (THE COURT REPORTER READ BACK THE 2 REQUESTED TESTIMONY.) 3 A. Answer, yes. 4 Q. In reading the memo, does that 5 reflect your recollection concerning whether or 6 not you were present at this meeting, Doctor 7 Talbott? 8 A. I can't recall if I was or 9 not, sir. 10 Q. Can you give any additions or 11 deletions to the contents of this memo? 12 A. No, sir. 13 Q. The memo says that at the FDA 14 Lilly agreed to do the following projects, 15 doesn't it? 16 A. Let's see, we're talking on 17 the first page, sir? 18 Q. Yes. 19 A. At the FDA meeting, Lilly 20 agreed to do the following projects, colon, 21 right. 22 Q. One, proceed with the 23 rechallenge study. 24 A. That's correct, sir, that's Page 212 1 the heading for one. 2 Q. Do you know if a rechallenge 3 study was ever done? 4 A. I don't know that, sir. 5 Q. Do you know if a rechallenge 6 study protocol was ever drafted? 7 A. No, I don't know whether one 8 was or not. 9 Q. I believe we testified -- you 10 testified earlier, that certainly you don't have 11 any recollection of formally submitting a 12 rechallenge protocol to the Food and Drug 13 Administration? 14 A. I believe that's an apt 15 characterization, sir, yes. 16 Q. And you don't have any 17 recollection of receiving any formal approval 18 from the Food and Drug Administration concerning 19 a rechallenge protocol? 20 A. I believe that has been my 21 testimony, yes, sir. 22 Q. The third bullet point under 23 item one says, we agreed to have the rechallenge 24 protocol ready to go by September 1st, 1991, Page 213 1 doesn't it? 2 A. Let's see here, we're talking 3 the first page, item number one. Yes, there are 4 little bullet points there. We agreed to have 5 the rechallenge protocol ready to go by September 6 1, 1991, that's correct, sir. 7 Q. It also says, and to provide 8 data after the first quarter which would provide 9 information on six months of experiences, doesn't 10 it? 11 A. Yes, it says that. Yes, it 12 does. You read that correctly. 13 Q. It also says in the next 14 sentence, this will allow the Food and Drug 15 Administration, or he says FDA and Lilly, to 16 determine if the study was feasible or not and to 17 give a feel for the data we were collecting if 18 patients were enrolled, doesn't it? 19 A. That's a correct reading, sir, 20 yes. 21 Q. Do you know whether or not the 22 rechallenge protocol was ready to go by September 23 1st, 1991, Doctor Talbott? 24 A. No, sir, I don't. Page 214 1 Q. Do you know if there was any 2 data collected in the first quarter of 1991 which 3 would provide information on six months of 4 experience in testing this drug in a rechallenge 5 basis on individuals who had had suicidal 6 ideation after being treated with Prozac? 7 MR. MYERS: Before he answers, let me 8 object to the form to the extent it makes any 9 difference, you reference the first quarter of 10 1991 and this was written in the second quarter 11 of 1991, so -- 12 MR. SMITH: I'm just quoting what the 13 document says. 14 A. I really don't understand what 15 he means by this, Mister Smith. I'm not trying 16 to be difficult, but I don't understand what he 17 means. Data after the first quarter which would 18 provide information on six months of experience, 19 I mean a quarter is three months, six months of 20 experience, I don't know what he's going after 21 there. So, I don't know. I guess to answer your 22 question, I don't know. 23 Q. You haven't seen any data 24 generated in connection with a rechallenge study, Page 215 1 have you, Doctor Talbott? 2 A. Not that I'm aware of, sir, 3 no. 4 Q. You would be aware, would you 5 not, as director of medical regulatory affairs, 6 if such data existed or exists? 7 A. It would be in the files, it 8 would be submitted as we discussed before through 9 my office. I don't recall every piece of 10 information that we submit to the agency, but the 11 application files would reflect if we indeed 12 submitted that. I don't recall any, but again 13 it's a recollection fact and the documents would 14 speak for themselves whether they were or were 15 not submitted. 16 Q. Did you see any such 17 information in the boxes of documents that you 18 reviewed in connection with giving your 19 deposition here in this case, Doctor Talbott? 20 A. I don't remember seeing much 21 of any clinical data at all, sir. 22 Q. So is the answer to my 23 question -- 24 A. The answer to your question is Page 216 1 no. 2 Q. The second point in that memo 3 says that, incorporated the modified scale for 4 suicidal ideation - revised, paren, MSSI dash R, 5 close paren, in ongoing and planned U.S. and UK 6 clinical trials. 7 A. That's correct, sir, that's 8 item number two. Did we have a question before 9 us, Mister Smith, I'm sorry? 10 Q. No, I'm getting some coffee. 11 A. Okay, I'm not trying to push. 12 Q. Is that what the second point 13 says? 14 A. The second point said, item 15 number two, incorporate the modified scale for 16 suicidal ideation, dash, revised, parentheses, 17 MSSI dash R, close parentheses, in ongoing and 18 planned U.S. and UK clinical trials, period. 19 Q. Do you know what a modified 20 scale for suicidal ideation is? 21 A. Other than what I can just 22 derive from the words themselves, a modified 23 scale for suicidal ideation, I don't know 24 anything about it practically, it's a clinical Page 217 1 scale apparently. 2 Q. Apparently, I think you 3 testified earlier, you don't know anything about 4 any scales or measurements of suicidal ideation. 5 A. Yes, I believe I recall that. 6 It was in regard to Exhibit Number 3, item number 7 two, I think. 8 Q. Did you ever see a protocol or 9 any plan submitted to the Food and Drug 10 Administration incorporating a modified scale for 11 suicidal ideation? 12 A. I don't recall any, sir, no. 13 Q. Did you ever see any data, or 14 any plan, or any proposal from a fellow by the 15 name of Ivan Miller, in connection with this? 16 A. No, that name doesn't ring a 17 bell at all. 18 Q. You never heard of Ivan 19 Miller? 20 A. I don't think so, no. 21 Q. Have you heard the term 22 validation study? 23 A. Validation study is kind of a 24 general term in science. You have a method -- do Page 218 1 you want me to explain it? 2 Q. Please. 3 A. Okay. You have a methodology, 4 whether it's rats or whatever, and you propose 5 this methodology and then you validate it against 6 an existing standard of some kind. So that's 7 what a validation study means to me. 8 Q. Is that good scientific 9 principle? 10 A. I think so, yes. 11 Q. On page two, item four -- 12 well, page one says, "At the FDA meeting, Lilly 13 agreed to do the following projects." I think 14 we've already established that you're not aware 15 of a rechallenge study being done? 16 A. I believe that was my previous 17 testimony, yes, sir. 18 Q. Number two is, are you aware 19 of any incorporation of a modified scale for 20 suicidal ideation revised? 21 A. When you say number two, sir, 22 are you referring to this memo? 23 Q. Yes, number two on page one of 24 the memo. Page 219 1 A. Okay. No, sir, I think I've 2 said I'm not aware of that. 3 Q. Do you know whether Lilly ever 4 complied with item three as they agreed to do, in 5 the use of MSSI dash R? 6 A. It may take a second, I will 7 review that paragraph. 8 Q. Sure. 9 A. I don't know that we ever did 10 that, sir. I don't have any information one way 11 or the other. 12 Q. Four indicates that Lilly 13 agreed to do a descriptive study of patients 14 reported to develop intensive violent suicidal 15 thoughts, doesn't it? 16 A. Give me a second, again, 17 Mister Smith, to read the paragraph. Actually, 18 they're talking a bit about a pilot study there. 19 I will just modify it a bit. It looked like we 20 had suggested after Doctor Stadel had made some 21 input that we think about a pilot, rather than a 22 full blown study. 23 Q. Was there any pilot study done 24 which you are aware? Page 220 1 A. I'm not aware of any, sir. 2 Q. Would a pilot study be a study 3 that would have to be submitted to the Food and 4 Drug Administration by Lilly? 5 A. I would think so, yes, sir. 6 Q. Would a pilot study be a study 7 that would have to be approved by the Food and 8 Drug Administration? 9 A. I would think so, sir. 10 Q. Do you know of any such pilot 11 study submitted or approved by the Food and Drug 12 Administration? 13 A. I don't recall any, sir. 14 Q. The middle paragraph there 15 says, Doctor Leber mentioned that it may be 16 worthwhile to determine what the risk, paren, 17 incidence, close paren, is of the development of 18 these symptoms in garden variety patients treated 19 for the first time with Fluoxetine versus other 20 agents. Do see that? 21 A. That's the sentence, yes, sir. 22 Q. Do you know whether or not 23 Lilly ever did any study to determine what the 24 risk is of development of these symptoms in, Page 221 1 quote, garden variety patients treated for the 2 first time with Fluoxetine versus other agents, 3 end quote? 4 A. I don't know what Doctor 5 Kotsanos meant by garden variety patients. I'm 6 having trouble with that. So I wouldn't know -- 7 I mean, if I don't know what kind of patient it 8 is, I can't really give you a good answer about 9 whether we ever did a study or not. 10 Q. You never saw a garden variety 11 protocol, did you? 12 A. If that's the question, sir, 13 the answer is no. 14 Q. Have you ever seen a protocol 15 in connection with Fluoxetine that called for 16 Prozac to be given to people who were mildly 17 depressed as opposed to severely depressed? 18 A. Again, I don't recall. We 19 make so many submissions I can't recall whether I 20 have seen that or not. The file -- the 21 application in the file would reflect whether it 22 was submitted or not. 23 Q. If there's not any there, it 24 wouldn't have been done. Page 222 1 A. To my understanding, that's 2 correct, sir. 3 Q. The last paragraph on Exhibit 4 4 says, the FDA mentioned three more items. 5 These included, one, they asked if we were 6 planning to develop a ten milligram dose. 7 Correct? 8 A. Yes, sir, that's item number 9 one, right at the bottom of the page. 10 Q. In May, 1991, is it correct 11 that Prozac was not available in a ten milligram 12 dose pulvule? 13 A. I believe that's correct, sir. 14 I believe the original approved version or the 15 one that was in force at that time was a twenty 16 milligram pulvule. 17 Q. And an individual couldn't -- 18 or a physician couldn't prescribe Prozac ten 19 milligrams in a capsule form -- pulvule form, I 20 think is what it's called. 21 A. Yes, pulvule, capsule, are 22 basically the same. Well, again, I'm not a 23 clinician, but I could see the situation where 24 you could, say, open a capsule, halve the Page 223 1 contents, put it in applesauce or orange juice or 2 something, I don't know, again I'm not a 3 clinician, and take half the capsule content. I 4 could see a physician doing that. 5 Q. Why would a physician do that? 6 MR. HARRIS: Objection, calls for 7 information beyond this witness's knowledge. 8 A. I think you would have to be a 9 doc to answer that. 10 Q. You said you could see it 11 being done. I just wondered under what 12 circumstance you could see it being done. 13 A. I think my answer was in 14 response to your question, could a physician 15 write a prescription, and my response was yes, he 16 or she could write a prescription because 17 physically he could separate the capsule. I 18 think they pull apart. I've never tried to do 19 it, but I think they look like they could. And 20 just halve the contents. So now, why would they 21 do that, that's beyond my capability to answer. 22 Q. In May, 1991, was Eli Lilly 23 and Company planning to develop a ten milligram 24 dose in the pulvule form? Page 224 1 A. I believe we had done some 2 development work on different dosage sizes, I 3 think ten milligram was in there. The answer to 4 the question, I guess, then would be yes. 5 Q. Had Eli Lilly and Company 6 filed an application, and I don't know what the 7 formal term of the application would be, to 8 manufacture Prozac in a different dosage state 9 that had been originally granted under the 10 original NDA? 11 A. I don't recall if we had done 12 that, but when were we talking about here, sir, 13 may of '91? I don't recall if we had made any 14 filings by that date, the application file would 15 show for us, I can't recall when the dates were 16 made -- whether the submissions were made. 17 Q. That submission would have 18 been made under your signature, wouldn't it? 19 A. That's correct, sir. 20 Q. Of course, we know now 21 physicians are able to prescribed Prozac to 22 patients in half that dosage that they originally 23 were allowed to, that is in the twenty milligram, 24 by now having ten milligram pulvules available Page 225 1 for physicians to prescribe. 2 A. Would you mind rephrasing 3 that? I'm sorry, I'm not sure what I'm 4 answering. 5 Q. We know now that doctors can 6 prescribe Prozac for patients for depression at 7 half the dosage originally approved and can 8 prescribe Prozac at ten milligrams now. 9 A. Are you asking me is ten 10 milligram dose size approved now? 11 Q. Yes. 12 A. I think it is, yes. 13 Q. Do you recall why Lilly chose 14 to request approval from the Food and Drug 15 Administration to manufacture Prozac in ten 16 milligram pulvules? 17 A. I don't know that I could 18 point to a specific document and say here's our 19 stated reason why. But generally, when you have 20 a range, an acceptable range of dosing like we 21 have on Fluoxetine that I think runs twenty do 22 eighty milligrams, you want to try to provide 23 flexibility for those increments as much as 24 possible. So if someone opted to maybe make a Page 226 1 thirty milligram prescription for somebody, they 2 could either give them a twenty and a ten or 3 three tens. And they wouldn't have to then 4 report to what I was talking earlier, splitting 5 open a capsule and trying to separate them. So 6 it gives us dosing flexibility. Did I answer 7 your question? 8 Q. It also gives us dosage 9 flexibility under twenty milligrams, too, doesn't 10 it, Doctor Talbott? 11 A. Certainly, you can take the 12 ten milligram. 13 Q. And the Food and Drug 14 Administration was inquiring about that in May of 15 1991, weren't they? 16 A. Let's see, go back to Exhibit 17 4, Doctor Kotsanos' memo. The FDA mentioned 18 three more items at the bottom of the page, the 19 items included -- item number one asked if we 20 were planning to develop a ten milligram dose. 21 Q. Doctor Talbott, are you aware 22 of any surveillance studies done on Fluoxetine or 23 Prozac? 24 A. I'm not sure if we conducted Page 227 1 any post-marketing surveillance or not. You 2 could say that the spontaneous adverse event 3 system that the agency uses and that we report to 4 is a surveillance mechanism. I'm not sure that I 5 would call it a study. 6 Q. No, an actual study designated 7 as a surveillance study. 8 A. As a post-marketing 9 surveillance study for Prozac? 10 Q. Yes, or in any way. 11 MR. MYERS: He used the word 12 surveillance and you're saying post-marketing 13 surveillance. I don't know if you all are 14 talking the same thing or not. 15 A. We may be talking past each 16 another. Tell me what you mean and I'll try to -- 17 Q. Well, have you seen any 18 submission to the Food and Drug Administration 19 designated with the numbers SOO1 or SOO2? 20 A. I think those are British 21 registry types of studies, is that what you're 22 referring to? 23 Q. Not that I know of. It would 24 have been something -- that would have been Page 228 1 something that would fit the United States Food 2 and Drug Administration. 3 MS. ZETTLER: Maybe I can clear it up. 4 We have been -- we don't have them with us today, 5 Doctor, but we have been shown drafts of 6 protocols with the designation for Prozac or 7 Fluoxetine and then the follow-up of SOO1 and 8 SOO2. It's been explained to us that these 9 studies are called or referred to within Lilly as 10 surveillance studies. The protocols that you 11 have been shown, Doctor, are for clinical trials 12 not for surveillance of preexisting data or 13 anything like that. Are you aware of any studies 14 like that? 15 THE WITNESS: That doesn't ring a bell 16 at all. 17 (PLAINTIFFS' EXHIBIT NO. 5 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. (BY MR. SMITH) Would you 21 review Exhibit 5? 22 A. Certainly. All right, sir, I 23 have read it. 24 Q. This takes us back in time a Page 229 1 ways, doesn't it? 2 A. October 4th, 1985, was the 3 date of the memo. 4 Q. And at that time were you the 5 director -- at that time were you a regulatory 6 scientist with Eli Lilly and Company? 7 A. That's my regulatory scientist 8 period, that's right, sir. 9 Q. And the -- you wrote the memo 10 designated as Exhibit 5, did you not? 11 A. Let's see that's number five, 12 yes, my name is down at the bottom. 13 Q. Do you recall writing this 14 memo? 15 A. No, I don't. 16 Q. Do you recall seeing this memo 17 in the collection of documents that you reviewed 18 in preparation for your deposition, either a few 19 months ago or a few weeks ago? 20 A. No, not really, sir. 21 Q. Does reading the document 22 refresh your recollection concerning the contents 23 of the document? 24 A. Uh-huh, it does. Page 230 1 Q. Now, in October of 1985, 2 Prozac had not been approved by the Food and Drug 3 Administration for sale to the American public, 4 had it? 5 A. That's correct, sir. 6 Q. And a doctor, in 1985, could 7 not prescribe Prozac, correct? 8 A. Here in the states, that's 9 correct, sir. 10 Q. Fluoxetine was being used and 11 had been used in clinical trials by Lilly 12 investigating this drug, had they not? 13 A. That's correct, sir. 14 Q. And the pivotal clinical 15 trials had been completed by October 4th, 1985, 16 had they not? 17 A. I can't give you exact dates 18 for their completion. I can only draw a 19 inference that, and it ties together, so bear 20 with me, that the clinical trials would have to 21 be completed, the trials reported into the NDA, 22 the NDA submitted to the agency, the agency then 23 far enough along in their review that they called 24 a meeting of the psychopharmacological drugs Page 231 1 advisory committee to consider the NDA. So the 2 answer to your question then is yes. 3 Q. So, the steps that needed to 4 be taken to get it to the advisory committee 5 stage had been completed, or were about -- 6 A. Steps of what now, sir, I'm 7 sorry? 8 Q. The steps in the approval 9 process had been completed. 10 A. The NDA? 11 Q. Yes. 12 A. That's correct, sir. 13 Q. Tell us about the 14 pharmacologic drugs advisory committee, what is 15 that? 16 A. Psychopharmacological drugs 17 advisory committee? 18 Q. Yes. 19 A. That's a committee comprised 20 of outside experts that provide advice to FDA on, 21 in this case, psychopharmacological drugs, but 22 there must be forty or fifty or sixty such 23 committees throughout the FDA to provide advice 24 on various kind of drugs, devices, what have you. Page 232 1 Q. So this is a specific 2 committee of experts that advise the Food and 3 Drug Administration in connection with 4 psychiatric drugs? 5 A. I would rather say 6 psychopharmacological drugs. 7 Q. Okay, psychopharmacological 8 drugs? 9 A. That's correct, sir. 10 Q. These are experts in 11 psychopharmacology? 12 A. Yes. 13 Q. Now, is the drugs -- is this 14 psychopharmacologic drug advisory committee, the 15 committee that approves Prozac for sale to the 16 public? 17 A. The agency uses these as 18 advisory committees. And the recommendations 19 from the advisory committees are not binding on 20 the agency. 21 Q. The Food and Drug 22 Administration approves or disapproves sale to 23 the public of a particular drug. 24 A. That's exactly right, that's Page 233 1 where I was headed. 2 Q. And the psychopharmacologic 3 drug advisory committee is just a committee of 4 experts that is used to give some additional 5 input into the issue with respect to whether, in 6 this instance, Prozac should be approved by the 7 FDA? 8 A. I would shade my answer to say 9 that, and you may not have meant this, but you 10 said it's just a committee of experts. I would 11 say it is a committee of experts and not try to 12 minimize them a bit. And also too, the agency 13 doesn't just get information, which I think is 14 the phraseology used, maybe not verbatim, but 15 they actually ask for a recommendation. So, it's 16 a little more formal, I think, than you just 17 characterized. 18 Q. Right. Well, at this meeting 19 that's being planned, that's the subject of this 20 memorandum -- 21 A. Right. 22 Q. -- there's going to be three 23 particular entities involved or groups meeting. 24 Number one will be those making presentations Page 234 1 from Eli Lilly and Company. 2 A. That's correct. 3 Q. Number two, there will be 4 representatives of the Food and Drug 5 Administration at this meeting. 6 A. That's correct. 7 Q. And number three, the members 8 of the psychopharmacologic drug advisory 9 committee will be present at this meeting. 10 A. Right. Those are three. 11 There are other entities. Was that your 12 question, are these the only three entities or 13 are these three entities there? 14 Q. Those three entities are 15 there, we know. 16 A. Were there in this case. 17 Q. What other entities would be 18 there? 19 A. There is a general audience. 20 These are open meetings, public open meetings. 21 Q. I understand that, but these 22 are the three entities that are going to have any 23 input into the decision making process. 24 A. Again, I don't mean to be Page 235 1 difficult, but there's a section of each of these 2 advisory committee meetings where people from the 3 audience, just John Q. Public Citizen can come 4 up and speak. So, if they ask the executive 5 secretary here, Mister Bramick, I guess it was, 6 they would have requested time to speak about any 7 issues before this committee, they would have had 8 that opportunity. 9 Q. All right. 10 A. So I'm -- I know it's probably 11 not that important, but I want to be as factual 12 as I can be. 13 Q. But the three main arms -- the 14 three arms that you know that are going to be 15 there, are going to be people from Lilly, people 16 from the Food and Drug Administration and actual 17 members of the psychopharmacologic drug advisory 18 committee itself. 19 A. That's correct, sir. 20 Q. Is it a requirement that the 21 psychopharmacologic drugs advisory committee 22 receive information on a drug like Prozac before 23 it's approved? 24 A. And you used the term Page 236 1 requirement, right? 2 Q. Yes. 3 A. There is actually not, if you 4 look at the regulations for drugs and the statute 5 associated for that, there is really not a 6 mandate that you take anything before an advisory 7 committee. Now interestingly enough, if you go 8 over and look at the medical device amendments, 9 and the statute that drove those and the enabling 10 regulation, they actually do mandate involvement 11 of advisory committees. So in answer to your 12 question, if we were talking devices I would say 13 yes, but since we are talking about drugs, there 14 is nothing that mandates that. 15 Q. In your experience from your 16 work with the Food and Drug Administration and 17 the psychopharmacologic drugs advisory committee 18 group, do you have an opinion concerning whether 19 or not the FDA considers the opinion of the 20 committee? 21 A. Okay. I want to give two 22 answers into actually they're essentially the 23 same. I think you asked me for my experience and 24 so that would go back to when I was on the device Page 237 1 side. And I know that when, not only because we 2 were mandated by the statutes to take advice 3 issues to these various advisory committees, but 4 also because of the level of expertise of the 5 people involved, we pay a great deal of 6 attention, so that was kind of a former device 7 person's view of it. Insofar as the agency, the 8 drug people's views now, all the public 9 utterances that I have seen, indicate that the 10 divisions, whether it's Doctor Leber or anybody 11 else on the drug side, put a great deal of stock 12 in what the advisory committee meeting said -- or 13 the advisory committee said, not just the 14 psychopharmacological. So there was a double yes 15 to your answer -- to your question. 16 Q. Now this memo reflects a 17 conversation you had with a Mister Fred Abramek. 18 A. You want me to help you with 19 that? Abramek. 20 Q. Abramek. Who was the 21 executive secretary of the pharmacologic drugs 22 advisory committee, is that right? 23 A. Mister Abramek was the 24 executive secretary of the psychopharmacologic Page 238 1 drugs advisory committee, that's right, sir. 2 Q. Mister Abramek is not an 3 employee of the Food and Drug Administration. 4 A. He isn't? 5 Q. Or is he? 6 A. You mean was he? 7 Q. Yes. 8 A. Then? 9 Q. Then. 10 A. Yes. 11 Q. I thought the pharmacologic 12 drug advisory committee was a separate group, 13 separate from the Food and Drug Administration? 14 A. Do you want me to get into the 15 explanation of that to help through this? I 16 don't know -- is that your thought? 17 MR. MYERS: What's the question? 18 A. Is that the question? Then I 19 can answer it. 20 Q. Yes. 21 A. The psychopharmacological 22 drugs advisory committee is established by, along 23 with the other drugs advisory committees, and 24 device advisory committees, is established by the Page 239 1 Food and Drug Administration and is administered 2 by the Food and Drug Administration, but these 3 are people who are brought into the agency's 4 advisory committee meetings from the outside, 5 they become special government employees, and it 6 is, in fact, an FDA body. Mister Abramek, I 7 don't know if he does now, that's why I asked 8 you, I didn't know if he was still at the agency 9 or not and that's why I responded the way I did, 10 Mister Abramek actually was a staff member in 11 Doctor Leber's division. And one of his duties -- 12 I believe he was one of these consumer safety 13 officers if memory serves me correctly that we 14 talked about earlier. One of his duties was to 15 administer as executive secretaries -- as an 16 executive secretary that advisory committee, in 17 other words agendas, meeting dates, locations, 18 rooms. Remember we talked a little bit earlier 19 about a CSO, that was involved with audio/visual 20 issues and the room and the agenda and the 21 meeting, et cetera, so that's parallel. He is, 22 in fact -- a long winded answer -- he is, in 23 fact, an FDA employee and members of the 24 psychopharmacological drugs advisory committee Page 240 1 and the other advisory committees of the FDA are 2 special government employees. So this is all FDA 3 stuff, all FDA operations. 4 Q. Those members of the advisory 5 committee, other than the executive -- does the 6 executive secretary sit on the advisory 7 committee? 8 A. I don't believe he is, sir. I 9 believe he's considered -- 10 Q. Ex officio? 11 A. Yes. That's appropriate, yes. 12 Q. These other members though, of 13 the advisory committee, these are private 14 individual citizens from around the country that 15 have a particular expertise in 16 psychopharmacologic drugs, are they not? 17 A. That's correct, sir. 18 Q. And they don't work full time 19 for the Food and Drug Administration, do they? 20 A. Not full time, that's correct, 21 sir. 22 Q. They're called upon to work on 23 special projects in connection with their -- in 24 connection with psychopharmacological drugs? Page 241 1 A. I don't know that I would 2 agree with -- it said just that way. 3 Q. How would you say it then? 4 A. I would say that they -- the 5 thing I'm having trouble with is special 6 projects. They serve on the committee and 7 generally review issues that the agency asks them 8 to review. A project to me is you start with 9 something, you build something, you complete it. 10 And this is a continuing thing. As you know, 11 some of these advisory committee meetings have 12 been around for twenty or thirty years, so it's 13 not a project to project to project to project, 14 it's a continuing thing. Otherwise I agree with 15 what you said. 16 Q. Do you know how much any of 17 the committee members are paid? 18 A. I think they get something 19 called per diem. When I was at the FDA, I think 20 they made about a hundred dollars a day. 21 Q. Do you know how much time 22 members of the psychopharmacologic drugs advisory 23 committee were devoting on the average to their 24 work in October of 1985? Page 242 1 A. Well, we can calculate because 2 there were normally three meetings of the 3 committee a year and normally two days per 4 meeting, so at least there were six. And then I 5 don't know if there were -- if they got -- if 6 they were given additional data to review. I'm 7 sure that they just didn't come there and review 8 it that day, they had additional data. So at 9 least six days a year, and probably more. 10 Q. All right. Had you known 11 Mister Abramek prior to October 1st, 1985? 12 A. Well, October 1st, that was 13 your question? 14 Q. Yes. 15 A. I believe that I had talked to 16 him because he was a consumer safety officer for 17 that division several times before, during that 18 year. That was my recollection. I don't think 19 that this was the first time that I ever talked 20 to the man. 21 Q. In these advisory committee 22 meetings, would they consider more than one drug 23 or would there be just one drug that would be the 24 subject of the meeting? Page 243 1 A. Normally, there was just one 2 at at time. They might work on a couple of 3 drugs, one one day and one the second day. They 4 normally had two day meetings. 5 Q. But this October 10th meeting 6 that was scheduled, that was the subject of this 7 memo, was just going to involve Prozac? 8 A. That was my understanding, 9 sir, yes. Or it's my recollection, it's my 10 recollection. 11 Q. You say in the memo, "I called 12 Mr. Abramek to finalize our arrangements for the 13 October 10 Committee meeting. He acknowledged 14 that he had received our documents to be provided 15 to the Committee. He inquired as to whether Dr. 16 Leber had contacted me for a review of 17 FDA's position on Prozac." Is that correct? 18 A. That's correct, sir, first 19 three sentence of the memo. 20 Q. You were calling him and then 21 he asked you if Doctor Leber had contacted you 22 for a review of the FDA's position on Prozac, is 23 that what you're saying there? 24 A. That's what he's saying. Page 244 1 Q. All right. Had the FDA taken 2 a position on Prozac in October of 1985? 3 A. Well, they had taken a 4 preliminary position on it. 5 Q. Which was? 6 A. Which was that it was 7 approvable. 8 Q. And when you say approvable, 9 you mean that the FDA felt that Lilly had 10 demonstrated safety and efficacy with respect to 11 Prozac in treatment of depression. 12 A. To me approvable means that we 13 had passed the preliminary hurdles. Because as 14 you can calculate along with me, it was another, 15 what, twenty-four or twenty-five months until the 16 final approval came. So this was a preliminary 17 hurdle. 18 Q. You go on to say -- 19 MR. MYERS: Are you through, Doctor 20 Talbott? 21 A. Yes, I was saying preliminary, 22 I was underscoring preliminary. 23 Q. You go on to say I indicated 24 that Doctor Leber and I had discussed the FDA Page 245 1 stance at length. 2 A. That's correct. 3 Q. To confirm that I had provided -- 4 I had been provided with all available 5 information by Doctor Leber, I recapped each 6 point raised during our conversation, Mister 7 Abramek indicated that all of the issues in FDA's 8 notes to the committee had been fully covered by 9 Doctor Leber. Correct? 10 A. That's what it says, sir. 11 Q. It looks to me like you and 12 Doctor Leber had been working closely up to that 13 point in connection with getting your positions 14 dovetailed with respect to what would go on at 15 the advisory committee meeting. 16 A. Oh, I disagree with 17 dovetailing. I'm a carpenter and there was no 18 dovetailing there at all. 19 Q. Well, it would be a joint -- 20 it would be a coordinated submission. 21 A. No, I wouldn't even agree with 22 that. 23 Q. Tell me then how it would 24 work. Page 246 1 A. Well, as a courtesy, since he 2 had already told the committee of the agency's 3 position, as is the normal want for FDA's 4 interaction with their advisory committee 5 meetings or advisory committees, whether it's 6 devices or drugs, the agency takes a position and 7 apprises the sponsor of that position prior to 8 the meeting itself, rather than walking in there 9 and finding out precisely what the FDA's position 10 is, because the agency wants to use that as an 11 opportunity to elicit information and data. So 12 if the agency has problems on an issue, they want 13 the company to know about that and bring data in 14 there responsive and the agency and the advisory 15 committee will evaluate whether those data are 16 indeed responsive. So, I wouldn't say it was 17 dovetailing. He told me his position and I told 18 him my position, and we didn't agree on every 19 point and I think that's reflected in the 20 discussion that took place at the advisory 21 committee meeting. 22 Q. I guess, maybe my experience 23 as a lawyer, in thinking of advisory committee 24 meeting hearing, I had assumed that each side was Page 247 1 going to present an independent argument to some 2 independent group, but my reading of this 3 indicates that that may not be accurate. 4 A. I think that's quite accurate, 5 it was very independent. 6 Q. Everybody's talking to 7 everybody concerning the details of the meeting 8 prior to the meeting occurring, aren't they? 9 A. Everybody is talking to 10 everybody? 11 Q. You're talking with the 12 executive director of the advisory committee, 13 aren't you? 14 A. No, I'm talking to the 15 executive secretary. 16 Q. Executive secretary of the 17 advisory committee, aren't you? 18 A. Right. 19 Q. And you're talking with Doctor 20 Leber of the FDA, right? 21 A. Right, two people. 22 Q. And you're advising Doctor 23 Leber of what Lilly's position is prior to the 24 meeting, correct? Page 248 1 A. That's correct. 2 Q. And Doctor Leber is advising 3 you, at Lilly, what the FDA's position is 4 concerning Prozac prior to the meeting, isn't it? 5 A. That it was preliminarily 6 approvable, that's correct, sir. 7 Q. And you are discussing both of 8 those facts with the executive secretary of the 9 advisory committee, who is indeed and in fact an 10 FDA staff member full time, isn't he? 11 A. I think we talked about that 12 earlier, that's correct. 13 Q. You go on to say, I queried 14 Mister Abramek as to whether he now saw any 15 negative connotations, insofar as the NDA's 16 approvability is concerned, in FDA's position. 17 He stated that he did not and that FDA was indeed 18 taking a position in the regard to the 19 application. Correct? 20 A. Well, let me see if I can take 21 a whack at it, okay. I queried Mister Abramek as 22 to whether he now saw any negative connotations, 23 parentheses, insofar as the NDA's approvability 24 is concerned, close parentheses, and FDA's Page 249 1 position, period. Second sentence, he stated 2 that he did not and that FDA was indeed taking a 3 positive position in regard to the application. 4 That's what it says there. 5 Q. Okay. So Lilly knew, and the 6 FDA knew going into this advisory committee 7 meeting on October 10th, 1985, that each entity 8 was taking the position that Prozac was 9 approvable, correct? 10 MR. MYERS: Let me object to the form 11 of the question, since it's not the applicant's 12 place to approve or disapprove or make something 13 approvable or not. So I don't think that's 14 accurate as to what he said or what that said. 15 A. I would say that our position 16 was that the drug was safe and effective. 17 Q. And that it should be 18 approved. 19 A. It should be approved, yes, 20 sir. 21 Q. Okay. 22 MR. MYERS: You're getting there. 23 A. The agency's position was that 24 it was preliminarily approvable, as we already Page 250 1 talked about not to long ago. Another 2 twenty-four months went by as they were then 3 considering the information from the advisory 4 committee and the information in the application 5 as they continued their review as to whether it 6 was indeed approvable or not. What went on here, 7 the interactions with Doctor Leber, myself, and 8 Mister Abramek, are exactly the same sorts of 9 interactions that go on at -- prior to every FDA 10 advisory committee meeting on drugs or devices 11 and probably has been just like this, at least 12 during the time that I have been aware of which 13 has been about twenty years. So this is no 14 special circumstance. 15 Q. It's not a special 16 circumstance, but everybody's got their act 17 together at the time the meeting is held and the 18 die is already cast, isn't it, Doctor Talbott? 19 A. Not at all. 20 MR. MYERS: Objection to the form. 21 Q. Well, Lilly was taking the 22 position that the drug was approvable, correct? 23 A. Not surprisingly. 24 Q. Because they wanted it Page 251 1 approved. 2 A. Yes. 3 Q. And the FDA, Doctor Leber was 4 taking the position prior to this meeting that 5 the drug was approvable, correct? 6 A. No, I don't agree with that. 7 I said preliminarily approvable. If he had been 8 approvable, Mister Smith, he would have issued us 9 on October 4th, or whenever I talked to Mister 10 Abramek, October 1, 1985, an approvable letter. 11 And if you will remember correctly, that 12 approvable letter for that application didn't 13 come to us for another two years. So 14 preliminarily approvable, time to take the 15 application before an advisory committee. 16 Q. Regardless of that, your last 17 sentence of the first paragraph says he, 18 referring to Doctor Leber, stated that he did not 19 and the FDA was indeed taking a position positive 20 in the regard to the application, correct? 21 A. That's what it says, but may I -- 22 Q. That's what you wrote, too, 23 isn't it? 24 A. No. Now, Mister Smith, let me Page 252 1 complete it, sir. I think what you said, he, 2 referring to Doctor Leber -- in fact, maybe I 3 should just ask for the question. 4 Q. Well, strike that. He would 5 have to be Mister Abramek? 6 A. Yes, exactly. 7 Q. Who is an FDA employee, staff 8 member, full time, correct? 9 A. Executive secretary, that's 10 correct, sir. 11 Q. But is also the executive 12 committee secretary of the advisory committee, 13 correct? 14 A. That's correct, sir. 15 Q. And he, Mister Abramek, stated 16 that he did not and that the FDA -- and that FDA 17 was indeed taking a positive position in regard 18 to the application, correct? 19 A. That's exactly -- that's 20 consistent with being preliminarily approvable, 21 which is the time that you take something to the 22 advisory committee. 23 Q. You go on to state, turning to 24 administrative issues, that you would have a Page 253 1 brief background on each of the presenters, 2 correct? 3 A. Bear with me a second, sir. 4 That's the second paragraph? 5 Q. Yes. 6 A. That's correct, sir, first 7 sentence second paragraph. 8 Q. Then you say, I then asked 9 whether the new committee members had yet been 10 selected. Are you talking about the members of 11 the advisory committee? 12 A. Actually you missed a sentence 13 there, does that mean -- 14 Q. No, it means I don't want to 15 talk about any of that. 16 A. All right, fair enough. The 17 question was, I then asked whether the new 18 committee members had as yet been selected. 19 That's in there, yes, sir. 20 Q. Is that correct? 21 A. Yes, sir. 22 Q. How many committee members 23 were there in 1985 in connection with the 24 psychopharmacological drugs advisory committee? Page 254 1 A. Well, we can go back and find 2 records, I'm sure, of advisory committee meetings 3 itself. 4 Q. Approximately? 5 A. A dozen. Is that 6 approximation good enough for you? 7 Q. Yes, if that's based on some 8 reason. 9 A. Yes, it's close. 10 Q. You say -- I'll quote you 11 again. 12 A. Okay. 13 Q. I then asked whether the new 14 committee members had yet been selected. 15 A. Correct, sir. 16 Q. Did you know that there were 17 going to be some new committee members? 18 A. When the agency -- they 19 publish, a couple of times a year, I guess, a 20 compilation of all the members of their advisory 21 committees, drugs, devices, tea tasting, the 22 whole gamut of advisory committees. And in these 23 then they put the dates that the individual's 24 term expires. And so we knew by looking at the Page 255 1 most recent one of these, and I'm not sure when 2 it came out but obviously predated this, but that 3 there would be at least two people whose term had 4 expired. 5 Q. Is there always going to be 6 two people's terms expire each year? 7 A. At least, at least. Maybe 8 more than that, Mister Smith. 9 Q. And he told you, Mister 10 Abramek told you, that there were new committee 11 members that were due to come on or did you know 12 that by some independent research, in these books 13 like you talked about? 14 A. We knew that there would be 15 two new ones coming on, we knew that. As we 16 follow the FDA and its processes, we know that 17 they move people into those slots. Just as soon 18 as one's out, another one's right in behind it. 19 So this was my guesstimate that there would be 20 somebody appointed by this point, knowing that 21 the meeting was, what, about ten days or so? 22 Q. Uh-huh. 23 A. Yes, about ten days or so. 24 And that they had already probably gotten them Page 256 1 cleared, and that they were ready to go and, in 2 fact, had gotten the data that we had submitted 3 to the agency in preparation for the committee 4 meeting. 5 Q. You say, I then asked whether 6 the new committee members had yet been selected. 7 A. Uh-huh. 8 Q. You go on to say, he shared 9 with me the fact that the two -- that two new 10 members had been selected, but not officially 11 announced. He agreed to share their names with 12 me on the condition that we not make the 13 information public until the FDA had a chance to 14 do so. FDA was expected to do this momentarily. 15 I agreed to this condition. Correct? 16 A. Okay. 17 Q. Is that what it says, Doctor 18 Talbott? 19 A. That's what it says and then 20 it says the new members are. 21 Q. All right. 22 A. That's correct, sir. 23 Q. Why did you ask Mister Abramek 24 to give you the names of the two new committee Page 257 1 members when they hadn't been officially 2 announced? 3 A. It was a process the agency 4 has done for years, especially when it comes to 5 that close a time. 6 Q. My question is, why did you 7 ask for the names of the two new committee 8 members when they had not been officially 9 announced? 10 A. My -- I knew that my superiors 11 would ask me if the agency had made any 12 selections to replace the two retiring members, 13 and if that information was available I wanted to 14 be able to have it. 15 Q. You go on to say that he 16 agreed to share their names with me on the 17 condition that we not make the information 18 public. 19 A. Exactly. 20 Q. Until the FDA had a chance to 21 do so. 22 A. Exactly. 23 Q. Why was he willing to share 24 with you, a member of a pharmaceutical firm, Page 258 1 information that he wasn't able to share with the 2 public? 3 MR. MYERS: Before he answers, let me 4 object to the form to the extent it may call for 5 him to speculate as to what the other person 6 meant or intended to do. But if you know, tell 7 him. 8 A. I really don't know what he 9 was after there because it appeared that this was 10 going to be made imminently. And I guess I could 11 assume that he didn't want us making a public 12 statement about two new members before the agency 13 would have a chance. 14 Q. Why would you be making a 15 public statement about two new members before the 16 FDA had a chance? 17 A. I wouldn't have the least 18 inclination to do it. 19 Q. Why would you even care who 20 the two new members were? 21 A. Well, let's separate the 22 questions. Why would I -- or would I make it 23 public. I have no reason to make it public, I 24 could care less about that. But remember I said Page 259 1 just a second ago, my superiors realized that two 2 of the members are retiring, and we were aware of 3 that, just by following the public documents, and 4 I knew that I would be asked if the agency, at 5 this very late date, ten days or so, less than 6 two weeks before the meeting, had filled those 7 positions. 8 MS. ZETTLER: Motion to strike as 9 nonresponsive. 10 Q. Why would you care the names 11 of those two members? 12 MR. MYERS: I object to the question, 13 it's been asked and answered at least twice. 14 MS. ZETTLER: No, it hasn't. 15 MR. MYERS: Just tell them once again, 16 Doctor Talbott. 17 A. My superiors would ask if the 18 agency had replaced the two retiring members and 19 I wanted to be able to tell them, in fact, they 20 had. 21 Q. I understand they might ask 22 you if the committee had replaced the members, 23 but what difference would it make who they had 24 replaced them with, Doctor Talbott? Page 260 1 A. It would make absolutely none 2 to me, sir. 3 Q. What would it make to your 4 superiors? 5 A. I don't know, sir, I'm afraid 6 you'll have to ask them. 7 Q. Then why were you asking and 8 securing the names of these individuals when 9 their names were not going to be available to the 10 public? 11 A. I told you that my superiors 12 would ask me if there had been people nominated 13 to replace the retiring members. I asked that 14 question, I found out who the names were, I don't 15 even believe anybody ever asked me. 16 Q. What difference would it make 17 who they were, what their names were? 18 MR. MYERS: Doctor Talbott, don't 19 answer that, you answered that twice. He's not 20 going to answer that again, Paul, I'm telling him 21 not to answer that question again. 22 MS. ZETTLER: Certify it. 23 MR. SMITH: Are you telling him not to 24 answer that question? Page 261 1 MR. MYERS: Again repetitively, ask 2 him another question. 3 MS. ZETTLER: Certify it. 4 (QUESTION CERTIFIED.) 5 Q. Were there other instances, 6 Doctor Talbott, when employees of the Food and 7 Drug Administration gave you information 8 concerning members of various agencies that 9 wasn't made available to the public? 10 A. I have not had any 11 circumstances like that. 12 Q. This was the only circumstance 13 where that occurred? 14 A. That involved me, that's 15 correct. 16 Q. Have you ever asked employees 17 of the Food and Drug Administration for 18 information that wasn't public information? 19 A. Not that I can recall. I 20 believe all of our other advisory committee 21 meetings haven't had any expired members -- or I 22 mean, retired members. 23 Q. I thought they all expired 24 after -- I thought there was members that expired Page 262 1 or retired every year. 2 A. There are many, but what had 3 happened was in those instances they had already 4 been nominated and named as we came up to them. 5 Q. Who were these two new members 6 of the advisory committee? 7 A. I don't recall. 8 MR. MYERS: That's likely a redaction 9 there. I'll get you a clean copy of that 10 document. 11 MR. SMITH: I want to talk to him 12 about it now. 13 MR. MYERS: I don't have the ability 14 to get that information now. 15 MR. SMITH: Then I'll have to reserve 16 time to question Doctor Talbott concerning these 17 individuals when I can see their names. 18 MR. MYERS: You can reserve all you 19 like. Doctor Talbott is here for his deposition 20 today and tommorrow. 21 MS. ZETTLER: So the record is clear, 22 we received a copy of what has been marked 23 Exhibit 5, with the names and locations of the 24 two replacements that were given to Doctor Page 263 1 Talbott by Mister Abramek redacted. 2 MR. MYERS: But as I indicated that it 3 was likely a redaction error which I said I would 4 get a clean copy. 5 Q. (BY MR. SMITH) Do you know if 6 any of the psychopharmacologic drug advisory 7 committee that sat on October 10th, 1985, were 8 also members of the psychopharmacologic drug 9 advisory committee that sat in September, 1991, 10 on the question of suicidality? 11 A. I can't remember if there were 12 any common members or not. 13 Q. It's the same committee, isn't 14 it? 15 A. Right, but that was a space 16 of, what, about six years. And as I said, we get 17 a lot of rotation every year so I can't remember 18 if they were the same ones or not, Mister Smith. 19 Q. You say you think there was a 20 dozen members of the committee? 21 A. To start off, right. 22 Q. And that there is two 23 potentially retiring at the end of each year? 24 A. No, I think my testimony was Page 264 1 that there were more than two each year. 2 Q. But in all likelihood, some of 3 the members of the psychopharmacologic drug 4 advisory committee that sat on October 10th, 5 1985, also sat in September, 1991? 6 A. I don't think I would feel 7 good giving you an affirmative answer to that, I 8 really don't know. 9 Q. Well, you're not going to 10 state positively that not any of the members -- 11 A. No, I wouldn't state 12 positively not, no, sir. 13 Q. Did you contact -- look at 14 page two. 15 A. Uh-huh. 16 Q. Did you contact either one of 17 these individuals that are listed on page two? 18 A. No, sir. 19 Q. How do you know that? 20 A. Well, first off, it was not my 21 approach to contact advisory committee members 22 before a meeting. So I would conclusively state 23 that I didn't contact these people at all. 24 Q. You don't even know who they Page 265 1 are, do you? 2 A. No, but I don't have to know 3 who they are. I'm saying I wouldn't normally 4 contact an advisory committee member directly. 5 Q. Why? 6 A. I think they work for the 7 agency, they don't work for me. Any contacts 8 that we would make for them, we would go through 9 the FDA. 10 Q. You didn't have any problem 11 contacting Doctor Leber and Doctor Temple and 12 Doctor Laughren who worked for the agency 13 throughout this application process, did you, 14 Doctor Talbott? 15 A. Absolutely not. But those are 16 different kinds of employees. 17 Q. So why would there be a 18 problem in contacting members of the advisory 19 committee? 20 A. Let's go back and remember the 21 types of employees we're talking about. Remember 22 we said that the advisory committee members, I 23 think was your term, were private individuals who 24 served, and I believe it was my term, as special Page 266 1 government employees. Which means maybe six, 2 eight, ten days a year they work for the 3 government. 4 Q. Are they supposed to be 5 independent? 6 A. Of whom? 7 Q. Of Eli Lilly and Company and 8 the Food and Drug Administration? 9 A. They are supposed to provide 10 the agency with advisory committee opinions, but 11 they are special government employees of the Food 12 and Drug Administration. 13 Q. Are those opinions supposed to 14 be independent with those opinions and positions 15 of the Food and Drug Administration? 16 A. You're saying independent of 17 and not necessarily asking are they supposed to 18 be different than, is that -- 19 Q. Well, is there judgment in 20 connection with approvability of a particular 21 product or drug that's going to be consumed by 22 the United States public supposed to be 23 independent of that judgment exercised by the 24 Food and Drug Administration? Page 267 1 A. Yes, it's an independent body. 2 Q. But they're paid by the Food 3 and Drug Administration, correct? 4 A. Special government employees. 5 Q. Are they made aware of the 6 FDA's position in advance of the advisory 7 committee hearing? 8 A. The FDA takes the position and 9 informs them of that, that's correct. 10 Q. Do you know if that was done -- 11 apparently it was done in October, 1985, wasn't 12 it? 13 A. That's the inference I draw, 14 yes, sir. 15 Q. Do you know if that was done 16 in September of 1991 with respect to the FDA's 17 position on suicidality in Prozac? 18 A. Again, remember, this is 19 looking at an application in '85, this was an 20 issue in '91. 21 Q. I understand. 22 A. I don't recall that the agency 23 did make a position, no, in '91, let me clarify. 24 MS. ZETTLER: I'm sorry, did you say Page 268 1 to your recollection that they did not? 2 THE WITNESS: Did not, that's right, 3 ma'am. 4 MS. ZETTLER: They did not make a 5 position? 6 THE WITNESS: In 1991, that's right. 7 Q. (BY MR. SMITH) Who appoints 8 these committee members of the 9 psychopharmacologic drug advisory committee? 10 A. There is an office, and the 11 name escapes me now, at FDA that's responsible 12 for making appointments and doing the appointing, 13 administration. But anyone within the Department 14 of Health and Human Services, I think it was in 15 1985, I don't think it changed, I don't remember 16 if it was Department of Health and Social 17 Services Department or Health and Human Services. 18 Well, anyway, anybody within the department can 19 make recommendation for appointments. Many times 20 it's the commissioner of the Food and Drug 21 Administration that makes the actual suggestions 22 for the appointment. 23 Q. Is there a panel whose 24 function it is to select and appoint or select Page 269 1 and nominate members for these various 2 committees? 3 A. There's not a panel to do as 4 you've said. There is an office at the FDA 5 though that handles the administration once the 6 nominations have been made by people within the 7 agency and within the department. 8 Q. But who comes up with the 9 individuals who can be nominated? Certainly, for 10 instance, now Doctor Kessler -- 11 A. Could. 12 Q. -- can't be -- I know he's the 13 one that probably makes the ultimate appointment, 14 but he couldn't be aware of everybody or who is 15 the most knowledgable individuals with respect to 16 psychopharmacologic drugs, could he? 17 A. I think your answer to the 18 question was who makes nominationations, and 19 Doctor Kessler could in fact. I agree with you, 20 he couldn't know about everybody who was an 21 expert on psychopharmacological drugs. 22 Q. So who is it that does submit 23 names for nomination? 24 A. People throughout the agency, Page 270 1 the division itself, the Center. 2 Q. The Center? 3 A. The Center For Drug Evaluation 4 And Research. 5 Q. Is that part of the agency? 6 A. Yes, that's the level right 7 below the FDA. The commissioner, the 8 commissioner's office, the undersecretary, the 9 assistant secretary, the secretary. I remember 10 when I was at FDA, Mister Califano was the 11 secretary then, he had made some recommendations 12 for various panels. 13 Q. Well, how does one get on the 14 list to be recommended? 15 MR. MYERS: You're not going to make 16 it, Paul. 17 Q. If I were -- if I felt like I 18 had some particular expertise by virtue of my 19 involvement in litigation with 20 psychopharmacologic drugs -- 21 A. Uh-huh. 22 Q. -- could I submit to them, 23 somebody, my resume and say I would like to be 24 considered to be a member of that advisory Page 271 1 committee? 2 A. Certainly. 3 Q. Would I direct that to the 4 Department of Health and Human Services, Food and 5 Drug Administration or what? 6 A. Well, frommy experience I have 7 seen them from the department, I have seen them 8 from the commissioner, I have seen them from 9 congressional sources, both sides, the House and 10 the Senate, and I've seen them from other 11 elements of the executive branch. I have seen 12 John Q. Public Citizen write in to whom it may 13 concern at the FDA, and say I am -- like you 14 said, I am, and provide your credentials, et 15 cetera, from all sorts of directions. 16 Q. Could Eli Lilly recommend 17 somebody to be on that committee? 18 A. Certainly, I think we could. 19 Q. Has Eli Lilly recommended that 20 somebody be a member of that committee? 21 A. Not that I am aware of. 22 Q. Is there any way an individual 23 can find out who's been nominated for a 24 particular committee and who nominated them? Page 272 1 A. Uh-huh, yes, I'm sorry, yes. 2 Q. How would you do that? 3 A. You would contact the office, 4 and again, the name escapes me. If it's really 5 important, I can find it. 6 Q. It is. 7 A. I can find it for Mister Myers 8 very easily. You can contact that office and you 9 could ask for whatever committee, you could say 10 people have been nominated, people that have been 11 chosen, people are still being held in reserve 12 for nominations, et cetera. 13 Q. And then it would also reflect 14 by whom they have been nominated? 15 A. I think it would, sir, yes. 16 Q. Would the minutes of the 17 advisory committee itself bear any information on 18 the individual's source of nomination? 19 MR. MYERS: Are we talking about this 20 advisory committee or advisory committees in 21 general? 22 Q. This advisory committee. 23 A. I can't recall whether 24 anything like that was said or not, sir. There Page 273 1 is a transcript available, I'm sure it would be 2 reflected in that. I can't recall though, Mister 3 Smith, in direct answer to your question. 4 Q. Now, if you go to page two of 5 your memo, it says Mister Abramek suggested that 6 Doctor Blank would probably be, quote, clear, end 7 quote, in time to participate in the meeting 8 semicolon. 9 A. Uh-huh. 10 Q. He was doubtful that Doctor 11 Blank would be able to participate in the 12 meeting. 13 A. That's what it says, sir, 14 correct. 15 Q. What did either Mister Abramek 16 mean or what did you understand Mister Abramek to 17 mean by the use of the term clear? 18 A. Well, I just have to give you 19 my understanding because, again, Mister Abramek 20 made the statement. But, I think what he was 21 referring to was the people who are nominated, 22 again we've talked about the nomination process, 23 are then looked at for credentials, I think 24 they're looked at for who nominated them, and Page 274 1 also looked at for -- probably contacted to 2 confirm their interest. Because if you or I were 3 nominated by a third party, it would be 4 presumptuous for them, the FDA to say, okay, 5 you're on the panel, without having contacted you 6 to see if you were interested or not. So I think 7 that there is a process of clearing and making 8 sure that the individual is appropriately 9 qualified for the position, is interested in the 10 position, and would be willing to serve. 11 Q. How about a conflict of 12 interest, Doctor Talbott, does anybody check to 13 see if members of the committee would have a 14 conflict of interest by serving on the committee? 15 A. I'm sure they would. 16 Q. Would that mean -- would that 17 be what he's talking about by cleared? 18 A. That's probably part of the 19 process, probably so. 20 Q. Here it says Doctor -- Mister 21 Abramek suggested that Doctor Blank would 22 probably be cleared in time to participate in the 23 meeting. 24 A. Uh-huh. Page 275 1 Q. Then he goes on to say he was 2 doubtful that Doctor -- and I assume this is 3 another doctor, correct? 4 A. That's my assumption too, yes. 5 Q. Would be able to -- he was 6 doubtful that Doctor Blank would be able to 7 participate in the meeting, right? 8 A. Second Doctor Blank for our 9 purposes. 10 Q. Yes. 11 A. That's correct, that's what it 12 says. 13 Q. Is it your assumption or was 14 it your understanding, at the time, that the 15 reason the second doctor wouldn't be able to 16 participate in the meeting is because of this 17 clearing process wouldn't have been complete? 18 A. That's what I draw from this, 19 yes. 20 Q. Or that the clearing process 21 would result in him being disqualified from 22 sitting on that particular meeting? 23 A. No, I can't testify to what I 24 thought then, but as I look back at this now, I Page 276 1 think your first explanation is the one I would 2 accept. 3 Q. Is it your testimony today, 4 Doctor Talbott, that you did not contact either 5 one of these individuals? 6 A. Yes, sir. 7 Q. Have you contacted either one 8 of them since October the 1st, 1985 as far as you 9 know? 10 A. No. In fact, I think I could 11 conclusively state that I have not talked to any 12 advisory committee member. 13 Q. Have you ever talked to Doctor 14 David Dunner, Doctor Talbott? 15 A. Who? 16 Q. Doctor David Dunner in Seattle 17 Washington. 18 A. I don't know, Mister Smith. 19 Q. Do you know who Doctor David 20 Dunner is? 21 A. No. 22 Q. Well, have you seen Doctor 23 David Dunner's name on clinical studies done for 24 Eli Lilly and Company? Page 277 1 A. I don't recognize that name at 2 all. 3 Q. Have you seen Doctor David 4 Dunner's name done on clinical studies in 5 connection with Prozac for Eli Lilly and Company? 6 A. I think I have indicated that 7 I don't recognize Doctor David Dunner's name at 8 all. 9 Q. I'm trying to help you. 10 A. I know. 11 Q. Do you know Doctor Dunner's 12 name by virtue of the fact that he's a member of 13 Eli Lilly's psychiatric advisory board? 14 A. No, sir. 15 Q. Do you know that Doctor David 16 Dunner served on the FDA's advisory committee 17 meeting in October -- I mean September, 1991? 18 A. No, sir, I don't know that. 19 Q. Do you know of anybody from 20 Lilly who's ever talked to these two individuals 21 that are listed on page two? 22 A. I don't believe that I could 23 recall any contact. 24 Q. Do you know, well -- Page 278 1 A. Are we on the record? 2 Q. No. 3 MR. SMITH: I'm directing it to Mister 4 Myers. Can we have a clean copy of this by 5 tommorrow? 6 MR. MYERS: If not a clean copy, I 7 will at least try to get the names over the 8 phone. 9 Q. You go on to say in the second 10 paragraph of page two, before concluding the 11 conversation, I reminded Mister Abramek that he 12 was going to try to provide us with FDA documents 13 related to the meeting, correct? 14 A. Let me see, that's the kind of 15 mid-paragraph there before concluding the 16 conversation, reminded Mister Abramek that he was 17 going to try to provide us with FDA documents 18 related to the meeting. That's correct, that's 19 the first sentence. 20 Q. So Mister Abramek was the 21 executive secretary for the 22 neuropsychopharmacologic drugs advisory 23 committee, correct? 24 A. Let me help you with that a Page 279 1 little bit, psychopharmacological drugs advisory 2 committee. 3 Q. Psychopharmacological drugs 4 advisory committee. He was executive secretary, 5 right? 6 A. That's correct, sir. 7 Q. He was a full-time FDA 8 employee, correct? 9 A. I believe I said that before, 10 yes, sir. 11 Q. And he was going to give you, 12 as a regulatory scientist, the FDA documents 13 related to the meeting prior to the meeting, 14 right? 15 A. And versions of the agenda, 16 the informational handouts that they put out for 17 the general public at the meeting and related 18 items. That's what I said, sir. 19 Q. But the general public doesn't 20 get this information in advance, do they, Doctor 21 Talbott? 22 A. The general public is not 23 testifying before the committee. 24 Q. I thought you said the general Page 280 1 public could appear and could testify before the 2 committees? 3 A. If they're so interested, 4 that's right, but they're not scheduled to, as we 5 were. 6 Q. How do you know they weren't 7 scheduled to? 8 A. Well -- 9 Q. I thought any interested 10 member of the public could appear at one of these 11 advisory committee meetings, all they had to do 12 was make arrangements with the executive 13 secretary or somebody? 14 A. Absolutely right. But thirty 15 days prior to the meeting, in this case the 16 advisory committee meeting, the agency publishes 17 in the Federal Register the notice about the 18 meeting and shows that we, Eli Lilly and Company, 19 are scheduled to be there, or at least our 20 application is scheduled to be discussed that day 21 and that we have an opportunity to comment, then 22 anybody else has an opportunity to comment. 23 We're the only people that are really scheduled, 24 maybe I'm constructing that too narrowly, but Page 281 1 we're the only people that are really scheduled 2 thirty days in advance to be there. 3 Q. Lets assume that I saw this 4 notice of this meeting in October of '85, in 5 advance thirty days prior to this. 6 A. Right. 7 Q. And that I said I want to be 8 on the agenda. 9 A. Right. 10 Q. As I understand it, you said I 11 could do that? 12 A. That's my understanding, sir. 13 Q. It's a public meeting, 14 correct? 15 A. Yes. 16 Q. The public can participate? 17 A. Oh, yes. 18 Q. Can give their views? 19 A. Oh, yes. 20 Q. Can the public get this FDA 21 documentation that you got in advance like you 22 did? 23 A. I imagine probably if you 24 called them up and asked for it, you would have. Page 282 1 Q. Do you know of any instance 2 where that's happened? 3 A. Well, I've always been with a 4 company, so I can't really speak as a private 5 individual. 6 Q. So I guess your answer would 7 be no, I don't know any instances where a member 8 of the public has gotten this information in 9 advance? 10 A. Okay. 11 Q. Is that correct? 12 A. That's my answer. 13 Q. You go on to say, "I asked Mr. 14 Abramek whether we could obtain copies of the FDA 15 reviews sent to the Committee. He told me that 16 Division policy prohibited this per se; however, 17 according to Mr. Abramek, the phone call from 18 Doctor Leber was the agency's way of providing us 19 with the salient elements of the reviews provided 20 to the Committee." Correct? 21 A. That's what it says here. 22 Q. Tell me if that doesn't 23 indicate that Lilly is getting treatment that 24 they normally shouldn't be receiving, Doctor Page 283 1 Talbott. 2 A. Oh, I don't agree with that at 3 all. 4 Q. You don't agree with that? 5 A. No, sir, I do not. 6 Q. Well, you go on to say in the 7 next sentence, "I told Mr. Abramek that this 8 approach was quite satisfactory and that we 9 appreciated him and Dr. Leber taking the time to 10 provide us with this information." Correct? 11 A. That's what it says, sir, yes. 12 Q. And then you pass all of this 13 memo on to a number of Lilly employees. 14 A. Right, actually two columns of 15 addressees there on that first page. 16 Q. How many people are listed in 17 this list of -- can you count them for me? 18 A. You want me to count them for 19 you? All right. You asked me to count the 20 number, twenty-five by my count. 21 Q. So this information that you 22 received from Mister Abramek, the executive 23 secretary, in connection with names of two 24 members of the psychopharmacologic drugs advisory Page 284 1 committee that is not going to be made public, 2 you made public to twenty-five members of your 3 co-employees of Eli Lilly and Company, correct? 4 A. I wouldn't agree with making 5 public. 6 Q. You made it known to them, 7 didn't you? 8 A. That's a different question. 9 Q. You wrote the memo and they 10 received copy. 11 A. I made it known to them, but I 12 think your original question was I made it 13 public. And I don't think that's a public 14 document. 15 Q. You made it public at least to 16 the individuals listed on here. 17 A. I think my response was I made 18 it known to them and I think that's the phrase 19 you used, as well. 20 Q. You also list NDA file here. 21 A. Uh-huh. 22 Q. Which NDA file are you talking 23 about? 24 A. It would be our NDA file. Page 285 1 Q. Did you submit this memo to 2 the Food and Drug Administration, Doctor Talbott? 3 A. I don't think I did. Because 4 it said filed, it doesn't say the application or 5 the NDS number. But again the application itself 6 would reflect whether I did or not. 7 Can we take a short break? 8 (A SHORT RECESS WAS TAKEN.) 9 Q. (BY MR. SMITH) I'm a little 10 confused, Doctor Talbott. You say, "I asked 11 Mister Abramek whether we could obtain copies of 12 the FDA reviews sent to the committee." Do you 13 see that? 14 A. Uh-huh, I see that, right. 15 Q. Are the FDA reviews some 16 specific document? 17 A. Well, usually the agency 18 produces -- each of the various review areas 19 produces a review document -- a report, review 20 report. And I didn't know whether those would 21 even be done at that time because, again, this is 22 kind of preliminarily approvable, so I didn't 23 know how far along they were and whether they 24 even had these or not. So they normally do Page 286 1 reviews and, in fact, when a drug is approved, 2 there is something put out called a summary basis 3 of approval that contains the reviews, which is 4 is available. So, I was wondering then if those 5 were available or not, he told me they weren't. 6 Q. But he told you that -- he 7 didn't tell you they weren't available, he says 8 the division policy prohibited him giving you 9 copies. 10 A. They weren't available to me. 11 That's what it meant. 12 Q. He didn't mean to imply that 13 they weren't available at all? 14 A. No, I wasn't -- you know, 15 again, I can't remember the conversation I had 16 with Mister Abramek, but looking here, it says 17 asked Mister Abramek whether we could obtain 18 copies of the FDA review sent to the committee. 19 He told me the division policy prohibited this, 20 per se. So I'm not sure whether they were even 21 available then or not. But even if they were, 22 they weren't available to me. That's my take on 23 it. 24 Q. But he told you Doctor Leber's Page 287 1 call to you was sufficient, correct? 2 A. Well, I think he was using 3 that to say that that was providing to us the 4 position that the agency was going to take in 5 their discussion the next week, ten days, 6 whatever it is there. 7 Q. If the Food and Drug 8 Administration has made their decision that the 9 product is approvable, as you say -- 10 A. Preliminarily, so, yes. 11 Q. Preliminarily approvable. And 12 if they've already transmitted that information 13 to the committee -- 14 A. Uh-huh. 15 Q. -- and if Lilly knows about 16 the fact that this has been done, and Lilly's 17 position is the same, that is that the drug 18 should be considered approvable? 19 A. Our position, I think, 20 originally when we went down the same line of 21 questioning, is that we take the position that 22 it's safe and effective. 23 Q. Which means approvable? 24 A. Actually, means approved. Page 288 1 Q. All right. And so you thought 2 you were even beyond what the FDA thought you 3 were at that point? 4 A. Well, lets back up. I'm not 5 trying to be difficult but I want to be certain 6 on this. The safety and efficacy is we feel it's 7 a safe and effective drug. The agency then 8 judges when it reaches approvable, whether a drug 9 is safe and effective or not. So we would 10 contend all the way along that that was the case 11 because we had accumulated all the data and made 12 all the analyses. But then we submitted it to 13 FDA to conduct their analyses and in preparation 14 for this advisory committee meeting then I would 15 say that they had reached the preliminarily 16 approvable stage. In October of '87, I believe, 17 it was they sent us a letter saying it was 18 approvable and ultimately was approved 19 twenty-four months after the advisory committee 20 meeting in December of '87. So that's the way I 21 put all that together. 22 Q. Why did you need an advisory 23 committee if the decision's already been made? 24 MR. MYERS: I object to the form. Page 289 1 When you say "the decision," which decision? 2 MR. SMITH: The decisions upon which 3 the subject is going to be the subject of the 4 meeting, whether or not this drug ought to be 5 prescribed to the public? 6 MR. MYERS: I object to the form, 7 because I don't think that accurately captures 8 his testimony so far on this subject. But if you 9 can answer the question, Doctor Talbott, answer 10 it. 11 A. No, I can't respond to that. 12 Q. You can't respond to that? 13 A. No. If you maybe perhaps 14 rephrase it, I would be glad to try. 15 Q. I tell you what, it appears to 16 me that the advisory committee functions as a 17 set-up deal, that it's a foregone conclusion 18 going in, Doctor Talbott, concerning what's going 19 to happen here. That the FDA, Lilly and advisory 20 committee already know, at least as reflected by 21 your letter of October 4th, 1985, that there is 22 not going to be any problems at this meeting. Is 23 that correct? 24 A. No, I disagree with that Page 290 1 completely. 2 Q. What problems came up at that 3 meeting? 4 A. I believe there were questions 5 about -- and again, you know, now we're talking 6 about, what, going on eight and half, nine years 7 ago, we'll have to rely on the transcript to 8 document this. But there were questions about 9 efficacy valuations, questions about safety 10 issues, questions about the trials, et cetera. 11 All you have to do, Mister Smith, is follow the 12 FDA for a little while and you'll realize that 13 because the agency reaches a position of 14 preliminary approvability on any drug, it doesn't 15 mean that the advisory committee will go along 16 with it at all. So I couldn't disagree more with 17 your statement. 18 Q. Did the advisory committee 19 ever take a position inconsistent with the FDA 20 with respect to Prozac and safety of Prozac? 21 MR. MYERS: I object to the form. Do 22 you mean this committee at this meeting? 23 MR. SMITH: Yes. 24 MR. MYERS: At this meeting? Page 291 1 MR. SMITH: Yes. 2 A. I think the committee, as I 3 recall, had a number of questions which were 4 discussed over the space of about eight or ten 5 hours, I don't remember exactly how long it went 6 but it went on all day, which eventually the 7 committee recommended the drug was approvable, it 8 showed safety and efficacy. I'm not sure that 9 they agreed with what the agency said on each and 10 every point. In fact, it would be kind of 11 uncharacteristic if they did. So speaking for 12 the one time that psychopharmacology drugs 13 advisory committee in 1985, reviewed the NDA for 14 Prozac for antidepressant use, the committee 15 ultimately concluded that it was a safe and 16 effective drug and recommended approval. 17 (PLAINTIFFS' EXHIBIT NO. 6 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 A. You want me to go ahead and 21 read it? 22 Q. Yes. Because I'm going to ask 23 you some questions. 24 A. All right, sir. Page 292 1 Q. This is another memo, isn't 2 it, Doctor Talbott, in connection with the 3 October 10, 1985, advisory committee meeting? 4 A. Yes, sir. Just the caption is 5 the October 4, 1985, telephone conversation with 6 Doctor Paul Leber, director, division of 7 neuropharmacologic drug products, FDA - NDA 8 18-936 Prozac (fluoxetine hydrochloride), dated 9 October 7, 1985, by me. 10 Q. Why did you feel it necessary 11 to read that entire caption, Doctor Talbott? 12 A. Well, you said another memo 13 and I want to be specific about what we were 14 talking about. 15 Q. Why couldn't you just say 16 yeah? Did I in any way misrepresent the subject 17 of this document? 18 A. No, I didn't mean to imply 19 that at all. I'm sorry if you took it that way, 20 I didn't mean that. 21 Q. There was a meeting on October 22 10th, 1985, in Maryland at the FDA with the 23 advisory committee, wasn't there? 24 A. It was a psychopharmacological Page 293 1 committees meeting, right. October 10, did you 2 say? 3 Q. Yes, 1985. 4 A. Right. 5 Q. And this came up in a 6 conversation with Doctor Leber with the FDA, 7 didn't it? This proposed meeting on October 10 -- 8 A. The upcoming meeting, right. 9 Q. -- came up in a conversation 10 that you had with him on October 4th, didn't it? 11 A. That's correct. 12 Q. And I guess Doctor Leber -- 13 you say he called on another issue. 14 A. Uh-huh, first sentence there. 15 Q. Do you recall whether or not 16 that other issue involved Prozac in any way? 17 A. Had it involved Prozac, I 18 would have most likely have included it in this 19 one. That would be my normal process rather than 20 write two different memos. 21 Q. Did Eli Lilly and Company have 22 other neuropsychopharmacological drugs under 23 submission at the FDA, at that time? 24 A. We had a number of IND's, we Page 294 1 had at least one additional NDA that I was aware 2 of, and we had another pending NDA at that time, 3 too. 4 Q. Would those have been before 5 Doctor Leber? 6 A. Uh-huh, yes. 7 Q. So you're suspecting he was 8 calling you on something to do with something in 9 connection with those? 10 A. That's what I have to infer, 11 sir, because as I said earlier, I believe if it 12 had been about Prozac, it would have been 13 included in this same memo. 14 Q. What was Doctor Leber's 15 position at this time? 16 A. As indicated, he was a 17 director. 18 Q. Director of what? 19 A. Division of 20 neuropharmacological drug products FDA. 21 Q. You say that right there, 22 don't you? 23 A. Well, you had taken offense at 24 my reading before and I was a little nervous, I'm Page 295 1 sorry. 2 Q. You say that Doctor Leber is 3 pleased that you were not going to be making a 4 lengthy presentation at this advisory committee 5 hearing, don't you? 6 A. Right. Just toward the bottom 7 of that paragraph, Doctor Leber stated that he 8 was pleased we were not making a lengthy 9 presentation. 10 Q. And he suggested that the FDA 11 wouldn't be using less than an hour for their 12 presentation as well? 13 A. That's why I suggested, my 14 recollection was it was longer. 15 Q. How long did that meeting 16 last? 17 A. I don't recall, I think the 18 transcript would reflect. It seemed like it went 19 on forever. 20 MS. ZETTLER: Kind of like today? 21 THE WITNESS: Is that on or off? 22 MR. MYERS: You may use that as a 23 point of reference. 24 THE WITNESS: About like today. Page 296 1 Q. Was it a morning and an 2 afternoon session? 3 A. That's my recollection, yes. 4 The transcript would show that though, the 5 starting and stop time. 6 Q. What was the problem then, if 7 you had less than an hour and Doctor Leber had 8 less than an hour, what took up all the other 9 time? 10 A. The committee asking 11 questions. 12 Q. On what, did the stock analyst 13 ask any questions? 14 A. No. I don't believe the stock 15 analyst said anything. 16 Q. Are stock analysts normally at 17 these advisory committee hearings? 18 A. Unfortunately so, more and 19 more. 20 Q. You say in your memo, first 21 sentence of paragraph two, I alerted Doctor Leber 22 to the fact that we had been given some 23 indication that a number of stock analysts might 24 be in the audience. I informed Doctor Leber that Page 297 1 due to some suggestion that Prozac may have some 2 utility as in anti-obesity indications, we would 3 not make any reference to weight gain or loss in 4 our presentation. You go on to say, Doctor Leber 5 agreed with this approach as long as we were 6 certain that no safety issues, that is severe 7 medically significant weight loss, existed. I 8 assured Doctor Leber that this was the case. 9 Correct? 10 A. That's correct, sir. 11 Q. Were the stock analysts going 12 to be there in connection with Prozac's use as a 13 potential anti-depressant or as a potential 14 anti-obesity medication? 15 MR. MYERS: Hold on, let me object to 16 the form of the question to the extent you would 17 make him speculate as to why certain undefined 18 stock analysts were there. 19 Q. You say in your memo, Doctor 20 Talbott, that you informed Doctor Leber that due 21 to some suggestion that Prozac may have some 22 utility as an anti-obesity indication. I took it 23 from that that the reason for the stock analysts 24 was that there was some indication of Prozac as a Page 298 1 potential fat medicine. 2 A. Or you mean anti-fat medicine. 3 Q. Or anti-fat medicine. 4 A. I can't remember exactly what, 5 obviously, what I was thinking when when I wrote 6 this. But in looking at it, it seems to me that 7 I wanted to be careful before we went into that 8 meeting, that Doctor Leber did not think that we 9 would use that occasion to tout FDA for something 10 that -- I don't think at that time we even had an 11 application before them or at least an NDA before 12 the FDA for any other indications. And that we 13 had learned -- in fact, I do recall how we had 14 learned that the stock analysts were going to be 15 there. Our securities, the person that handles 16 interactions with the financial community, had 17 gotten a lot of calls from financial analysts who 18 said they were going to be at the meeting, and he 19 called me and said they were going to be there. 20 And this was all very new to us, because at least 21 in my experience with dealing with advisory 22 committee meetings, stock analysts, I mean, they 23 had no place there. And so this was new to us 24 and that's why I called and shared it with Doctor Page 299 1 Leber. I didn't want him to think that we would 2 then use that as a kind of a testimonial for 3 other indications for Prozac. That's what I 4 think really went on here. I do remember the 5 stimulus of the fact we knew the stock analysts 6 would be there. 7 Q. Do you know whether or not 8 anything was done to call the stock analysts and 9 ask them not to be at this presentation? 10 A. I don't know -- you know, if 11 it could have been done, I think that would have 12 been excellent, because I don't think -- stock 13 analysts are abhorent to me, especially at 14 scientific presentations. 15 Q. Well, but the stock analysts 16 were there because they thought as early as 17 October 1985, that Prozac might have some 18 potential for weight loss, didn't they? 19 MR. MYERS: Same objection as to the 20 form. Tell him, if you know. 21 MR. HARRIS: Same objection. 22 A. I don't agree with that. I 23 think they were there to see whether the 24 committee recommended approval or not and what Page 300 1 the FDA had to say and what we had to say. But 2 then again, I can't prove that, that's just 3 speculation on my part. 4 Q. The reason I talk about weight 5 loss is because of -- by virtue of the language 6 that you use, Doctor Talbott, do you see that? 7 A. I understand that. 8 Q. Do you have any recollection 9 what the effect of this advisory committee 10 meeting had on Lilly's stock, the value of 11 Lilly's stock? 12 A. I'm sure it probably went up 13 afterwards. 14 Q. You did attend the meeting? 15 A. The '85? 16 Q. Yes. 17 A. Yes. 18 Q. Were there indeed stock 19 analysts there, or people who looked like stock 20 analysts to you? 21 A. Well, don't come to the next 22 question is what does a stock analyst look like, 23 okay. I'll answer, if you don't ask that 24 question. There were some people there that Page 301 1 didn't look like scientists and physicians, how 2 is that, and I don't think they were attorneys. 3 Now don't ask me for any more on that one. 4 Q. Did any members of the public 5 speak at this advisory committee meeting, Doctor 6 Talbott? 7 A. I don't recall, Mister Smith, 8 one way or the other, sir, I'm sorry. Again the 9 transcript would reflect that. 10 Q. The last paragraph of this 11 October 7th memo states, although I did not use 12 this conversation to again query Doctor Leber as 13 to the FDA's position on Prozac safety and 14 efficacy, all of Doctor Leber's comments were 15 consistent with the FDA's previously stated 16 positive position on the NDA. Correct? 17 A. Correct, sir, that's what it 18 says. 19 Q. Why did it take twenty-four 20 months from the time of the advisory committee 21 hearing until the FDA issued the approvable 22 letter? 23 A. Well, as we said a little bit 24 earlier, go back to the preliminarily approvable Page 302 1 position that the agency had as they went into 2 the advisory committee meeting, that they needed 3 time then to go through each of the studies and 4 all the data, to go further down in, and 5 preliminary approvable is like looking at the 6 upper third of the pyramid, maybe. And deciding 7 whether -- historically the agency has been able 8 to decide whether to go to an advisory committee 9 meeting or not after that sort of preliminary 10 approvable review. And then based on what came 11 back at the advisory committee meeting and then 12 based on the agency's continuing review over the 13 next twelve, twenty-four months, et cetera, in 14 this case, they then would decide whether it's 15 actually approvable or not. And as we know, they 16 they did in October of '87, sent us a letter to 17 that effect, and then finally approved it the end 18 of December. I think if you look at the data or 19 the amount of time between advisory committee 20 meeting and final approval, this was not terribly 21 short, this was not terribly long, it was kind of 22 terribly average. 23 (PLAINTIFF'S EXHIBIT NUMBER 7 24 WAS MARKED FOR IDENTIFICATION AND Page 303 1 RECEIVED IN EVIDENCE.) 2 Q. Do you recognize what's been 3 marked as Exhibit 7? 4 A. It's number 7, yes, sir. Let 5 me look for just a second and I won't take long. 6 Q. I'm just going to ask you some 7 general questions about that. 8 A. To recall it, I mean it's just 9 another document, but Ms. Potvin indicates that 10 it's the copy of the summary provided the FDA for 11 distribution to the members of the advisory 12 committee, it's in September which is three weeks 13 or so before the advisory committee meeting, so 14 that's probably what it is. 15 Q. And Ms. Potvin, the author of 16 this transmittal letter, is under you -- was 17 under you in September, 1985, wasn't she? 18 A. I'd call this a cover memo, 19 not a cover letter. I don't know, Mister Smith, 20 I'm not sure if she was or not in '85. At one 21 time the medical writers did report to me, but 22 I'm not sure if they did in '85. I don't believe 23 they did, in fact, I think they were in another 24 part of medical. Page 304 1 Q. This was something going to 2 the Food and Drug Administration, isn't it? 3 A. Yes. 4 Q. It's going to be used at the 5 advisory committee? 6 A. Right. 7 Q. And you are copied on this 8 document? 9 A. Right. 10 Q. Certainly this would have been 11 something that came through your office? 12 A. Right. 13 Q. And she wouldn't have sent 14 something off to the FDA without your approval? 15 A. No. And, in fact, I don't 16 think she would have sent it, I would have sent 17 it. 18 Q. And is it your judgment that 19 this is basically what was sent to the FDA? 20 A. I have to accept that it is, 21 sir. I can't recall it. It looks like the sort 22 of document that one would prepare for that 23 situation, yes. 24 Q. And this document is for Page 305 1 distribution to the members of the advisory 2 committee, is it not? 3 A. Yes, I believe that's right 4 there in the first sentence, that's correct, sir. 5 Q. The word suicide, suicidal 6 ideation is not mentioned at all in this 7 document, is it? 8 A. I'm sorry? 9 Q. The word suicide or suicidal 10 ideation is not mentioned at all in this 11 document, is it? 12 MR. MYERS: Let me object to the form, 13 the document speaks for itself, it either says it 14 or it doesn't. 15 A. I would have to read it and 16 look for the word. I don't know, the document is 17 here, it says what it says. 18 Q. Look under clinical safety. 19 A. All right. 20 Q. Wouldn't that be where -- 21 A. What page is it on? 22 Q. Page 6. Wouldn't that be 23 where suicide might be mentioned or adverse 24 reactions might be happening? Page 306 1 A. It could be mentioned there, 2 yes. 3 Q. It says safety indicates a 4 bunch of things here, don't they? 5 A. It talks about safety studies 6 indicate that on what, three, six, seven, bullets 7 after that, mid-page? 8 Q. Yes. Suicide is not mentioned 9 in any one of these, is it? 10 A. It's not under any of those 11 seven points on page six. 12 Q. Aside from the subject of 13 suicide, would you take my word for it, suicide 14 is not mentioned in the document, but the 15 document will speak for itself. Turn to page 16 five. The document there states, about two 17 thirds of the way down, the middle of the page, 18 Fluoxetine relieves anxiety associated with 19 depression, doesn't it? 20 A. What did you say about halfway 21 down? Okay. Right, major bullet point, 22 Fluoxetine relieves anxiety associated with 23 depression. And there is four lines there. 24 Q. Sub-bullet point under there Page 307 1 it says anxiety associated with depression was 2 relieved as much with Fluoxetine as with what 3 other anti-depressant? 4 A. You want me to pronounce that 5 for you? Imipramine. 6 Q. No. I can pronounce that. 7 A. Okay, I'm sorry. 8 Q. That's one of the few I can 9 pronounce. I was just trying to shorten this and 10 say they mention some other anti-depressants, 11 don't they? 12 A. Right, at least one there, 13 Imipramine. 14 Q. It says there under the next 15 bullet point, that Fluoxetine is effective in 16 retarded and agitated patients, doesn't it? 17 A. Yes, sir, that's a major 18 bullet point and there are five or six lines 19 underneath that. 20 Q. And so the information that 21 the advisory committee received from Lilly at the 22 committee hearing was that Fluoxetine relieves 23 anxiety associated with depression and that 24 Fluoxetine is effective in retarded and agitated Page 308 1 patients. 2 A. Those are the points, that's 3 correct, sir. 4 MR. SMITH: It's five o'clock, 5 exactly, according to my watch. 6 (THE DEPOSITION WAS ADJOURNED 7 AND RESUMED THE FOLLOWING DAY, AS FOLLOWS:) 8 9 10 11 * * * * * * * * * * 12 EXAMINATION 13 BY MS. ZETTLER: 14 Q. Doctor, you understand you're 15 still under oath? 16 A. Yes, ma'am. 17 Q. And you understand that the 18 rules that Paul laid out at the beginning of the 19 deposition still apply today as far as if you 20 don't understand one of my questions, ask me to 21 repeat it, if you need to take a break, things of 22 that nature? 23 A. Certainly, I appreciate that. 24 Q. Like Mister Harris, my voice Page 309 1 seems to be getting a little bit scratchy here, 2 so if I have problems understanding you, please 3 let me know. 4 A. I will. 5 Q. You're stuck with me today. 6 Paul bailed on me, so you're stuck with me. Just 7 a couple of follow-up questions from yesterday's 8 portion of the deposition. Do you recall what 9 position Hans Weber held within Lilly at the time 10 of Exhibit 1, November of 1990? 11 A. Let me check my records, just 12 a second. I believe at that time, Ms. Zettler, 13 he was the medical director for our German 14 affiliate. 15 Q. How about Doctor Bouchy? 16 A. I'm not sure whether it was 17 doctor or not, and I didn't get a chance to go 18 back and check that last night. I'm sorry, I was 19 going to, but it just got away from me. He had 20 some function, I believe, not on the medical side 21 or scientific side, but on the administrative and 22 business management side in Europe. 23 Q. At that time, in 1990? 24 A. I believe so, yes, ma'am. Page 310 1 Q. Is that still true today, as 2 far as you know? 3 A. I really don't know where 4 Claude is now. In fact, I'm not sure if he's 5 even with the company still, I don't remember. 6 Q. That's one thing I wanted to 7 clear up. One of the depositions, I can't 8 remember who it is off-hand, maybe Allen Webber, 9 they thought that a Claude Bouchy had left the 10 company. 11 A. I couldn't comment. I have 12 not seen or heard from him in quite a while, so 13 that's possible. 14 Q. When was the last time that 15 you talked to Hans Weber? 16 A. I probably talked to Hans 17 either -- you mean talk or via messenger, 18 something like that? 19 Q. Actually talked to him. 20 A. Actually talked to him, oh. 21 Oh, probably we had a phone conversation in the 22 last six months, but I wouldn't say it was very 23 recently. 24 Q. When was the last time that Page 311 1 Doctor Weber was here in Indianapolis? 2 A. Hans, you mean, of course? 3 Q. Right. 4 A. Maybe within the last year. I 5 think there was a medical directors' meeting that 6 all the affiliate medical directors came in for, 7 it's been within the last year. It strikes me it 8 was in June of last year, but I'm not sure. 9 Q. Are medical director meetings 10 held fairly regularly? 11 A. I think once every six months. 12 Q. Is he here for those 13 generally? 14 A. They're not always here. I 15 gave the impression that they're always here, 16 they're not, it just happened to be this 17 particular time. They are around the U.S. -- 18 well, not around, in the U.S. and in Europe, and 19 twice a year, I think, is the frequency on that. 20 Q. Do you know when the next 21 medical directors' meeting is? 22 A. No, I don't. 23 Q. Do you know where it will be 24 held? Page 312 1 A. No, I don't know that either. 2 I don't attend these, so I don't keep it on my 3 calendar. 4 Q. Do you know when the next time 5 Doctor Hans Weber plans on being in Indianapolis? 6 A. No, ma'am, I don't. 7 Q. How about the U.S., generally? 8 A. I don't have any idea, I'm 9 sorry. 10 MR. BROWN: I guess you're going to 11 have to use the Hague Convention to get him. 12 MS. ZETTLER: No, I think I'll go to 13 Germany. 14 THE WITNESS: Bad Hamburg is 15 beautiful. 16 (DISCUSSION OFF THE RECORD.) 17 Q. (BY MS. ZETTLER) Do you know 18 if the current German package insert for 19 Fluoxetine has been submitted to the FDA? 20 A. The current one, no, I don't 21 know whether that one has or not. 22 Q. Is it Lilly's policy to submit 23 yearly, or anytime, its updated package inserts 24 from other countries to the FDA? Page 313 1 A. Not normally, no. 2 Q. What circumstances will a 3 package insert be submitted? 4 A. Usually it's part of a safety 5 update or in preapproval sorts of documentation, 6 consistent with the regulations. 7 Q. How often are safety updates 8 filed once a drug is marketed in the United 9 States? 10 A. In the United States, Ms. 11 Zettler, it's quarterly for the first three 12 years, and then it's annually thereafter. 13 Q. Are foreign country package 14 inserts routinely submitted with every safety 15 update? 16 A. With post-approval safety 17 updates, not necessarily, no. 18 Q. What situation would a package 19 insert from another country be submitted with a 20 post-approval safety update? 21 A. I can't give you an exact 22 instance, but for example sometimes the agency 23 will make as a part of their approval conditions 24 the fact that you will provide package inserts Page 314 1 for X number of months -- or X number of safety 2 updates or X number of years, et cetera, and it 3 would be under those conditions. 4 Q. Do you know if they did that 5 in this instance? 6 A. I can't recall. 7 Q. Would that be in the 8 approvable letter? 9 A. I think it should be in the 10 approvable -- I'm sorry, I misunderstood you. It 11 should be in the approval letter. 12 Q. Approval? 13 A. Approval, as opposed to 14 approvable. 15 Q. When did that letter come with 16 regards to Fluoxetine? 17 A. The approval letter, I 18 believe, was in the last week of December of 19 1987. 20 Q. And the approvable letter came 21 out in September of '87? 22 A. I believe it was, yes, ma'am. 23 Q. What's the difference between 24 approvable and approval letter? Page 315 1 A. Let's track back from 2 approval. Approval is the -- Mister Smith and I 3 yesterday talked about the new drug application 4 being essentially a sponsor's application for 5 marketing rights for a new drug, and so the 6 approval letter grants you those rights, and you 7 can start selling the drug the next day. The 8 approvable letter is really at the ninety-nine 9 point nine percent completion point of the 10 overall review when there are some remaining 11 questions that the agency wants to get concluded, 12 as they complete their internal reviews, prepare 13 the documents associated with those, et cetera. 14 So generally, the approvable letter will contain 15 several pages of questions that a firm then is 16 asked to address before the approval letter is 17 finally granted. 18 Q. So the request to submit on 19 package inserts would be contained in the 20 approval or approvable letter? 21 A. It could be in either. It 22 could be in the approvable letter as part of 23 final information or it could be in the approval 24 letter as one of many conditions of approval, Page 316 1 there are always conditions of approval. 2 Q. Doctor, are you aware that 3 you've been designated as an expert witness in 4 the Fentress versus Shea Communications case in 5 Louisville, Kentucky? 6 A. I don't believe so, no. 7 Q. Have you heard of Joseph 8 Wesbecker? 9 A. Wesbecker, yes. 10 Q. Are you aware that you've been 11 designated as an expert witness in that case? 12 A. No. 13 Q. Has anybody asked you to 14 render opinions in that case or any other Prozac 15 case through testimony at trial? 16 A. No. 17 Q. Have you reviewed any of the 18 Wesbecker specific documents such as his medical 19 records and things of that nature? 20 A. I don't recall that, no. 21 MR. MYERS: Nancy, just for the 22 record, I will tell you that Doctor Talbott is 23 not going to render any opinions in the Wesbecker 24 case concerning Joseph Wesbecker, his medical Page 317 1 care and treatment by Doctor Coleman or any other 2 medical doctor. The purpose of his designation, 3 as we have tried to explain in the past, would be 4 to testify to the matters that he's been 5 testifying about here today, and that he's 6 testified about in the past with respect to FDA 7 regulations. I don't know how else to explain 8 it, but that is the purposes of his designation, 9 he's going to testify about the regulatory 10 matters that he's been testifying about for the 11 last couple of days, he is not going to give any 12 opinions about Mister Joseph Wesbecker or 13 causation or things like that. 14 MS. ZETTLER: So the the record is 15 clear, it's our position that regardless of 16 whether or not his opinions are going to relate 17 directly to causal relationship to Fluoxetine and 18 Joseph Wesbecker's actions, the court has ruled 19 that if you plan on eliciting any opinion 20 testimony from Doctor Talbott that hasn't been 21 discussed during this deposition through our 22 questioning, then you're going to be barred from 23 eliciting his opinion at trial. 24 MR. MYERS: I know the order about Page 318 1 which you speak, and I don't necessarily agree 2 with your characterization, but I understand that 3 there's an order that governs that issue and we, 4 of course, will be governed by what that order 5 says. 6 Q. (BY MS. ZETTLER) Okay. 7 Yesterday you told Paul that you had reviewed 8 approximately three boxes of documents? 9 A. Four, actually. 10 Q. Four boxes of documents in 11 preparation for yesterday and today's deposition 12 as well as the deposition that we started last 13 time when you became ill? 14 A. Right. 15 Q. Did you ask to see those 16 documents? 17 A. Yes, ma'am. 18 Q. Did you ask for any specific 19 document to see? 20 A. Well, let me add on to that. 21 I asked for my documents insofar as specific 22 documents. 23 Q. When you say your documents, 24 what do you mean? Page 319 1 A. Documents that I had 2 accumulated or that had been represented to me as 3 having been given to yourself and Mister Smith as 4 part of my deposition. 5 Q. Periodically, since the early 6 '90s, Lilly employees have been asked to turn 7 over documents to the legal department, documents 8 related to Fluoxetine? 9 A. Exactly, and that was those 10 documents. 11 Q. So you asked to see the legal 12 department's accumulation of all your documents 13 that you turned over in the years? 14 A. That's correct. 15 Q. Generally which documents do 16 you recall from your review of those documents? 17 MR. MYERS: Let me object to the form 18 because he said he looked at four boxes of 19 documents. 20 Q. I'm asking generally. Can you 21 give me general categories? 22 A. Sure, I can do that. Memos of 23 meetings, electronic mail messages, transmittal 24 letters, I think was the term we used yesterday, Page 320 1 things like that. It was, you know -- to ask me 2 about a specific document, you know, do you 3 recall the 23rd of May memo that you sent to 4 Doctor Jones, if I see it in front of me, I might 5 be able to, but just with that sort of caption, I 6 couldn't. But you asked for general, and that's 7 the sort of thing I looked at. 8 Q. Did you see within that four 9 boxes of documents submissions to the FDA under 10 your signature? 11 A. It seemed like there were some 12 transmittal letters in there. 13 Q. The letters themselves or were 14 the documents actually attached? 15 A. All I can remember is the 16 actual transmittal letters. There could have 17 been things attached to them. 18 Q. A substantial amount of the 19 communications and transmittals that have gone to 20 the FDA since you became involved with Fluoxetine 21 in 1985 have gone under your signature, correct? 22 A. Right. 23 Q. Have you looked at every 24 single one of those transmissions since your Page 321 1 involvement in Fluoxetine in 1985? 2 MR. MYERS: Wait a minute. When you 3 say transmission, do you mean the letters that he 4 wrote or all the stuff that -- 5 MS. ZETTLER: All the stuff that was 6 attached to it also. 7 A. Let me clarify, if I may. You 8 mean since they were submitted? 9 Q. Strike that, it was a bad 10 question. I guess what I'm asking is did you -- 11 does your file at the legal department at Lilly 12 contain all the submissions that you have made or 13 that have been made to the FDA by Lilly under 14 your signature? 15 A. No, it would be much more than 16 four boxes then. But those would be, as we 17 discussed at the beginning, actually, of our 18 testimony yesterday, those would be in what we 19 call the IND and NDA files. 20 Q. Okay. We've seen a number of 21 documents where people have signed your name or 22 signed their name on your signature line on 23 transmittal letters or other communications with 24 the FDA. Page 322 1 A. Yes. 2 Q. Why is it that somebody, say, 3 like Doctor Weber or Doctor Zerbe would sign your 4 name as opposed to using their own signature or 5 own signature line on the letter? 6 A. I think primarily to provide 7 some continuity on documentation, in other words 8 letters from me go to FDA, and it's easy for 9 people then to use that process. Or letters to 10 the FDA go from me would be more appropriate. 11 Q. Are these people required to 12 contact you before they send out a letter with 13 your signature on it letting you know that 14 they're doing so? 15 A. Yes. 16 Q. So Doctor Zerbe would contact 17 you and say Max, I'm going to send this note to 18 the FDA under your signature, but I'm going to 19 sign it Bob Zerbe on behalf of Max Talbott. 20 A. Right. A situation like that 21 might be when I was away from the office and I 22 call in. Doctor Zerbe, for example, and I know 23 this to be the case many times, would say we're 24 sending this letter to so and so, I'm going to Page 323 1 sign for you if that's okay, and I would 2 authorize it. 3 Q. Do you know of any occasion 4 where somebody has sent something over your 5 signature without getting your permission first? 6 A. I'm not aware of that. 7 Q. Were there certain people who 8 were allowed to do that and other people who were 9 not, in other words were there a couple of people 10 designated to sign in your absence? 11 A. Not by name, but by position. 12 Q. What position? 13 A. Okay. The regulatory 14 scientist would be, and then my supervisor would 15 be, for example Doctor Zerbe, Doctor Thompson, 16 Doctor Perelman, I believe, who was president of 17 the labs, et cetera -- or not et cetera, those 18 specifically. 19 Q. How about Doctor 20 Heiligenstein? 21 A. Heiligenstein, I'm not sure 22 that he was in that group. There may have been a 23 special occasion when he would contact me, but he 24 was not in that group that we would generally Page 324 1 use. 2 Q. Okay. Obviously you gave a 3 deposition yesterday, the first part of this 4 deposition yesterday, and then we tried to get 5 one underway a few months back and you became 6 ill, and I'm also aware of one other occasion 7 where Paul has deposed you. Other than those 8 occasions, have you given depositions in any 9 other Prozac cases? 10 A. I'm not aware of any. I don't 11 think so, Ms. Zettler. 12 Q. Did you review the first 13 portion of your deposition from last time, the 14 little short one? 15 MR. MYERS: January 13th, 1994. 16 THE WITNESS: Was that January? 17 A. Yes, I did. 18 Q. Do you recall any substantive 19 changes that you made to the testimony you gave 20 them? 21 A. I don't think I did, no. 22 Q. In the IND and NDA files at 23 Lilly yesterday, you talked briefly with Paul 24 about how everything that is turned over to the Page 325 1 FDA is contained in the files. In addition, 2 there were things not turned over to the FDA that 3 Lilly keeps either in the IND or NDA file, 4 depending on what it relates to. 5 A. Right. The reportable 6 information is in what we call the application, 7 and then documents that we have associated with 8 those applications, but which are not required to 9 be reported to the FDA, are in an additional file 10 there. So we refer to the whole thing as an IND 11 file, and for the purposes of my conversation 12 with Mister Smith yesterday, we said those things 13 that were required to be submitted were submitted 14 to the FDA with the application, whether it's the 15 IND or NDA. 16 Q. The non-application documents 17 that were in the file, are they kept separately 18 from the rest of the things -- 19 A. You mean physically? 20 Q. Right. 21 A. You know, I have not actually 22 looked at those. I would imagine they would be, 23 though. 24 Q. Do you know -- Page 326 1 A. In the same area, though. 2 Q. Same location? 3 A. Yes, ma'am. 4 Q. Do you know how they are 5 organized? And I'm talking about the 6 non-application NDA or IND document. 7 A. No, ma'am, I don't. It would 8 be, I know, by the IND number or NDA number, but 9 beyond that I don't know. 10 Q. You don't know if the 11 correspondence is kept in a separate file from 12 meeting minutes or if everything is just 13 organized chronologically, things of that nature? 14 A. No, I don't. I couldn't help 15 you on that, I'm sorry. 16 Q. Can you tell me what a summary 17 basis for approval is as opposed to approvable 18 letter or approval letter? 19 A. Certainly. The summary basis 20 of approval really is a compilation of the 21 preclinical review, the manufacturing and control 22 review, the statistical review, and the clinical 23 review with kind of an overview of all the 24 reviews as prepared by the FDA division or Page 327 1 divisions doing the review of a new drug 2 application. So that's the summary basis of 3 approval. And I think you asked me also for 4 approval letter and approvable letter. The 5 approval letter is the ultimate approval for 6 marketing of a new drug, it contains a listing of 7 all the submissions that have been made to that 8 application, and then it contains any conditions 9 of approval that have to be met in conjunction 10 with the marketing of that drug. 11 And then prior to that, you 12 have an approvable letter which says that a 13 preliminary finding or actually a reasonably 14 finalized finding of safety and efficacy has been 15 made by the agency, and that to complete this 16 process, the following information is needed. 17 And then there will be questions, probably 18 generally from all of the different areas that 19 are represented in review, preclinical, 20 manufacturing control, statistical, and clinical. 21 Q. So the summary basis for 22 approval is a document that's put together by the 23 FDA as opposed to Lilly? 24 A. That's correct. Page 328 1 Q. Do you know when the SBA came 2 out on Fluoxetine? 3 A. I don't recall. 4 Q. Obviously it was part of the 5 approvable letter, correct? 6 A. No, the summary basis of 7 approval actually comes out after approval, it's 8 completed by the agency before. 9 Q. So it came out after December 10 of 1987? 11 A. That's correct. 12 Q. Have you ever met with Doctor 13 Martin Teicher? 14 A. No, ma'am, I haven't. 15 Q. Have you spoken with him? 16 A. No, ma'am. 17 Q. Have you ever communicated 18 with him in any way? 19 A. Not that I'm aware of. 20 Q. Do you know if anybody at 21 Lilly has communicated with Doctor Teicher? 22 A. I believe some of our 23 physicians have, yes, ma'am. 24 Q. Who? Page 329 1 A. I believe that Doctor 2 Tollefson has, I believe that Doctor Zerbe did, I 3 can't recall if anyone else has. I know that no 4 one from regulatory affairs has, though. 5 Q. How about Doctor Beasley? 6 A. I wouldn't know. 7 Q. Do you know the circumstances 8 under which Doctor Tollefson and Doctor Beasley 9 communicated with Doctor Teicher? 10 A. I didn't know that Doctor 11 Beasley had. 12 Q. I'm sorry, Doctor Zerbe and 13 Doctor Tollefson. 14 A. I believe it was in 15 conjunction to the doctor's article. 16 Q. Do you know if they met with 17 him in person or they spoke with him on the 18 phone? 19 A. All I know is that those two, 20 I think, were in communication with him. I don't 21 know if they flew out there or talked to him or 22 what -- talked to him by phone, I mean, or what. 23 Q. Are there any limitations as 24 far as what types of information can be submitted Page 330 1 to the IND as opposed to what types of 2 information can be submitted to the NDA? 3 A. I don't think that the agency 4 restricts submission, no, to the IND. 5 Q. How about to the NDA? 6 A. I don't believe, in just 7 trying to page back over the Part 314 8 regulations, I don't believe there's any 9 prohibition against submission in there. 10 Q. Are you familiar with the 11 phrase Freedom of Information Act Request? 12 A. Yes, ma'am. 13 Q. Can you tell me what your 14 understanding of that is? 15 A. I believe that there is a law 16 that requires government agencies, and I think it 17 applies to the U.S. government agencies, to 18 release upon request information about government 19 actions, et cetera. That's it. As you know, I'm 20 not an attorney, so that's the extent of my 21 understanding of it. 22 Q. To your knowledge is the FDA, 23 in some cases, required to disclose information 24 to the public under such a request? Page 331 1 A. In fact, I believe that the 2 agency is -- I think that the Act requires them 3 to release the information unless there's another 4 law or regulation that prevents that. In other 5 words, it's not that the agency kind of picks and 6 chooses what it would release, but I think the 7 law itself says that you will release all 8 information unless -- maybe that's a difference 9 without a distinction, but I feel better 10 describing my understanding of it that way. 11 Q. Do you know if there is a 12 greater limitation on what can be released from 13 the IND as opposed to what can be released from 14 the NDA through a Freedom of Information Act 15 request? 16 A. I don't know how to respond to 17 that. I would think that probably the Act would 18 apply to all government documents to include 19 those held by FDA, so I'm not sure there would be 20 a distinction on an IND versus an NDA. 21 Q. You're familiar with such 22 things like trade secret, things of that nature? 23 A. I understand the term, yes. 24 Q. Obviously there's some Page 332 1 information that, for propriety reasons, or 2 reasons of competitiveness between your company 3 and other companies, your company may not want to 4 have disclosed? 5 A. Right. 6 Q. Do you know if such 7 information would be more likely to be found in 8 the IND as opposed to the NDA by virtue of the 9 fact that the IND is earlier in the development 10 process and testing process? 11 MR. MYERS: When you say such 12 information, you mean proprietary information 13 that we might not want released? 14 MS. ZETTLER: Right. 15 A. That's an interesting 16 question, I really never thought of it posed that 17 way. I guess the way that I would respond is 18 that because the NDA is so massively larger than 19 the IND, I mean just on sheer bulk, there's 20 probably more commercial, confidential commercial 21 information just by virtue of mass if nothing 22 else in the NDA than the IND. So there's 23 probably more information that could be legally 24 withheld from an FOI request in the NDA than the Page 333 1 IND. I'm not sure that I answered your question 2 to your satisfaction. 3 Q. You did. Do you know of any 4 regulations that govern what information does not 5 have to be disclosed under a FOI request? 6 A. I think you used the term 7 confidential, commercial and trade secret. Those 8 are terms that I've heard that don't have to be 9 released. And I also think, and I think I read 10 this in a trade sheet, that if there's a law 11 enforcement investigation underway, whether by 12 the FBI or Treasury Department or FDA or 13 whatever, that those data don't have to be 14 released. And certainly we can understand why 15 that would be the case. 16 Q. You mean those specific 17 agencies' investigation data? 18 A. You know more than I do, then, 19 at that point. So I would just assume that 20 common sense would say that if there's an FBI 21 operation underway, people that think they might 22 be under that operation could request FOI 23 information and find out what the federal agents 24 were doing. Hypothetical, of course. Page 334 1 Q. Do you consider yourself an 2 expert in FDA regulations? 3 A. Well, that's embarrassing to 4 refer to yourself as an expert. I think I know 5 them as well as anybody in a position such as 6 mine within the industry in the United States, 7 yes, ma'am. 8 Q. The regulations that you dealt 9 with as an employee of the FDA were regulations 10 pertaining to medical devices as opposed to 11 pharmaceuticals, correct? 12 A. Primarily, yes, but there were 13 many regulations that applied to both, not only 14 pharmaceuticals and devices, but to biologics, 15 vaccines, as well. 16 Q. Could you give me an idea of 17 what devices? 18 A. Certainly a lot of the 19 investigational requirements, such as patient 20 protection provisions, informed consents, 21 institutional review boards. Many of the 22 elements of investigational protocols, et cetera, 23 were the same between the devices and the drug 24 side. In fact, the device people pretty much Page 335 1 utilized the drug regulations as a template. 2 Q. If Lilly was involved in a 3 study that wasn't being done at Lilly, a clinical 4 trial on humans, and wasn't commissioned by Lilly 5 necessarily, but was done in conjunction with 6 Lilly -- 7 A. Uh-huh. 8 Q. -- would Lilly still have to 9 submit a protocol for that clinical trial to the 10 FDA for approval? 11 MR. MYERS: Before he answers, when 12 you say involved in conjunction with, I'm going 13 to object to the form because I don't know that 14 you defined that activity. 15 MS. ZETTLER: Doctor Talbott 16 understood the question. 17 A. No, actually I have a habit, 18 unfortunately, of nodding as people go along, but 19 sometimes they conclude that that means I 20 understand or agree. Can you give me a little 21 more precise definition of what you're talking 22 about? 23 Q. Sure. We have testimony from 24 other Lilly employees that a study was conducted Page 336 1 by Ivan Miller to validate a suicidality scale 2 that he had developed in conjunction with Lilly. 3 A. Okay. 4 Q. We don't know at this point if 5 it was something that was actually commissioned 6 or paid for by Lilly, I mean the study to 7 validate the scale. But in that situation, say, 8 where Lilly helped to develop or worked with 9 Doctor Miller to develop the suicidality scale, 10 would a protocol to validate that study still 11 have to be submitted to the FDA by Lilly? 12 MR. MYERS: To validate the study or 13 the scale? 14 MS. ZETTLER: The scale, I'm sorry. 15 A. The scale. It depends, and if 16 I may elaborate on that. 17 Q. Sure. 18 A. I think if Doctor -- was it 19 Miller? Because none of this rings a bell. I 20 think Mister Smith referred to Doctor Miller 21 yesterday, but short of that I don't recall that 22 name. But I think if Doctor Miller were to 23 proceed as the primary investigator and get what 24 we call an investigator's IND with the agency, Page 337 1 then I'm not sure that the regulations would 2 mandate that we submitted that protocol. 3 However, if we were to be the sponsors of that 4 study under the provisions of Part 312, the IND 5 regs, then I would think that we would be 6 required to submit a protocol. 7 Q. Would such a study be subject 8 to the IND regs as opposed to the NDA regs if it 9 was done postmarketing? 10 A. The regulations are not 11 terribly specific on that, but most often if it's 12 not exactly parallel to how the drug would be 13 used for the approved indications, then it would 14 have to be part of the IND. There are some 15 sections of applicability, both preceding -- 16 well, at the beginning of Part 3, and then also 17 these are elaborated on in Part 314 or the NDA 18 regs, as well, and these are almost like a 19 checklist. If dum, dum, dum, A, B, C, for 20 example, then you must submit an IND. And if 21 not, you're not required to so long as -- and 22 then there are conditions. 23 Q. If a rechallenge study had 24 been developed by Lilly that you were talking Page 338 1 about to Paul yesterday -- 2 A. Yes, ma'am. 3 Q. -- would that be submitted to 4 the IND or NDA for approval? 5 A. It would probably be submitted -- 6 since it would be an investigational study, I 7 would think it would probably be submitted to the 8 IND with a cross-file or a cross-copy to the NDA 9 for informational basis. 10 Q. You wouldn't have to get 11 approval under both the IND and NDA? 12 A. I don't believe that it would 13 be necessary under the NDA for a study because if 14 the IND requirements, actually, and the wording 15 is a bit archaic at the beginning, but what it 16 really says is it's an investigational new drug 17 exemption from the rules that pertain to 18 marketing new drugs. So under that construct, 19 then you would probably not need an NDA approval 20 for the study because you had already gotten an 21 exception under the IND. 22 Q. Are there regulations that 23 govern how information is to be delivered to the 24 FDA, in other words do you have to go through a Page 339 1 specific document control department or things of 2 that nature? 3 A. Not regulations, per se, no. 4 Q. Is there a practice at the FDA 5 that you have to go through document control 6 before you can get to the specific divisions? 7 A. Right, they have adopted some 8 procedures, and we try to stay informed of those 9 procedures. Obviously we don't want documents 10 going to the wrong place. 11 Q. Have you ever found a problem 12 with the document control division at the FDA 13 that deals with Doctor Leber's division of the 14 FDA? 15 A. On occasion, I have seen some 16 memoranda, in fact I believe in preparing for 17 this deposition, and I don't remember, it may 18 have actually been from me, but I think there was 19 a comment about the fact that people at FDA said 20 that the document control room had lost something 21 or misplaced something. So on the basis of that, 22 I have to answer yes, that at least I know of one 23 instance or I'm aware of one instance in which 24 there was a problem. Page 340 1 Q. Do you recall what document 2 that was? 3 A. No, I don't, but I'm sure my 4 documents would reflect it. 5 Q. Have you or anybody else 6 working with you or under you ever circumvented 7 the document control division at the FDA to 8 deliver document directly to, say, Doctor Leber, 9 Doctor Laughren, or anybody on his staff? 10 MR. MYERS: Let me either object to 11 the form or ask, when you say circumvent, do you 12 mean not filed something with that room or you 13 mean brought something to them in addition to 14 what you would have filed? 15 MS. ZETTLER: Not filed something 16 through them. 17 A. I wouldn't -- we wouldn't 18 circumvent anything there. I would add that we 19 may have taken desk copies to some people within 20 the division, but not have circumvented the 21 document control room. We'll go through the 22 normal filing process because the agency is 23 pretty adamant that unless something is 24 officially filed, and in the case of new drug Page 341 1 applications and even IND submissions, they will 2 give you filing letters that confirm that 3 something has been filed. So on the basis of 4 that, then, it behooves us really to use the 5 document control room, even if on occasion 6 something is lost. And in addition, if we want 7 other people to have copies directly or 8 additional copies, many times -- you know, we're 9 only supposed to submit two or three copies, 10 well, people within the division might want 11 additional copies for division staff, and so we 12 would, perhaps, by desk copies, provide those. 13 But we wouldn't circumvent the document control 14 room. 15 Q. So you would bring copies to 16 be filed with the document control room as well 17 hand-deliver copies to various -- 18 A. Probably at the same time, 19 yes. 20 Q. How about information that was 21 submitted to the 1991 psychopharmacological drug 22 advisory committee? 23 A. Okay, what do you mean how 24 about? Page 342 1 Q. Did you file information that 2 was provided to committee members regarding 3 Fluoxetine and suicidality or violent/aggressive 4 behavior with the document control room and then 5 provide additional copies to the committee 6 members? 7 A. I don't remember what the 8 process was. I'm sure there should be some pages 9 or transmittal letters or something that would 10 show that. 11 Q. Is that type of information, 12 information to be given to the advisory 13 committee, something that had to be filed or 14 procedurally should have been filed with the 15 control room? 16 A. I don't know that it would 17 have to be because I'm not sure you're actually 18 submitting it to an application. Clearly you 19 would not want to send it directly to the members 20 themselves because you would want to move it 21 through the FDA channels, and the FDA is pretty 22 adamant about anything that goes to the advisory 23 committees, has come into the agency itself, but 24 I'm not sure that that would be have to be filed Page 343 1 in the application. 2 Q. If it had to be filed, what 3 should it be filed under, the IND or NDA? 4 A. If it had to be filed, under 5 that circumstance I would say probably the NDA 6 because in the instance we're talking about, it's 7 a post-approval matter. 8 Q. Why would that be 9 post-approval matter and a validation of a 10 suicidality scale would not? 11 A. The study, as I indicated, 12 would need to be submitted to the IND if the 13 exact use circumstances for approval were not 14 followed in the study. In other words, if you do 15 everything according to the package insert, and 16 then also according to the caveats we talked 17 about earlier, in Part 312 and 314, then it would 18 be exempt from an IND. However, if there is any 19 variation at all from the approved indications 20 and use circumstances, and it did not meet any of 21 those caveats, then it would be considered 22 investigational and must be submitted to the IND. 23 Q. Would studies conducted on the 24 use of Fluoxetine in treating, say, Page 344 1 obsessive-compulsive disorder after the drug has 2 been approved for use with depression -- 3 A. Uh-huh. 4 Q. -- would that be submitted to 5 the depression IND or NDA or would that have its 6 own separate IND or NDA number? 7 A. The agency -- it wouldn't be 8 submitted to an NDA, I can answer that part of 9 it, but then I have an elaborate a bit on the IND 10 part. The agency has evolved their thinking 11 about assignment of IND numbers. Let's say early 12 on in the last decade they would try to get as 13 many different studies and indications, even, 14 under a single IND as possible. And my 15 understanding for them doing that was it was 16 easier for them to administer under a single file 17 number than it would be under a whole sequence of 18 files. Somewhere in the last half of the last 19 decade, they started to shift toward assigning a 20 lot of IND numbers. So let's say that we would 21 have an IND for depression, since we're talking 22 about Prozac, then we very may well have an IND 23 number for OCD, we might have an IND number for 24 bulimia, et cetera, et cetera. So a long-winded Page 345 1 answer to your question, then, is OCD studies 2 would probably be filed to their own separate IND 3 depending upon where they came in this evolution, 4 and in the FDA's administration. But I think 5 that it would be submitted to an IND, and it just 6 depends on whether the agency's administrative 7 approach would be to put it under a depression 8 IND or to assign its own separate IND. 9 Q. If it was assigned to some 10 separate IND, could the firm rely on information 11 that was submitted under the depression IND 12 anyway? 13 A. We can make reference to that. 14 I don't think that we could assume, I think we 15 have to actually say that the information under 16 IND one, two, three, Prozac for depression, is 17 referenced for this new IND. 18 Q. But for instance you wouldn't 19 have to reinvent the wheel, you wouldn't have to 20 conduct the same animal studies over again to 21 demonstrate the inhibition of seratonin reuptake, 22 say, manufacturing types of testing, things of 23 that nature, you wouldn't have to redo all that, 24 would you? Page 346 1 A. I'll answer in the affirmative 2 if we can make the question more general. I'm 3 not an expert on preclinical, but in general the 4 applicable work conducted for the preceding 5 indication could be referenced for the new one, 6 you're correct. 7 Q. How about human studies, could 8 you reference any of the depression human studies 9 for something, say, like OCD or obesity? 10 A. To the extent -- and again, 11 I'm out of my element here, but to the extent 12 that the clinical information would be comparable 13 from an efficacy point of view, you might be able 14 to. I think any exposure to the new molecular 15 entity could be relied upon by the agency as 16 indication of safety, in other words you have 17 human experience preceding your new IND. 18 MS. ZETTLER: Let's take a quick 19 break. 20 (A SHORT RECESS WAS TAKEN.) 21 Q. Doctor, do you recall 22 yesterday testifying about a rechallenge study 23 being considered by Lilly prior to the 1991 24 product or drug advisory committee meeting? Page 347 1 A. As I recall, there was a memo 2 to use the term -- actually several memos used 3 challenge, rechallenge, et cetera, yes, ma'am, in 4 that time frame. 5 Q. And it's your recollection 6 that the study was dropped after the 1991 7 advisory committee meeting because of the results 8 of the committee meeting or what was discussed at 9 the committee meeting -- 10 MR. MYERS: I object to the form, I 11 don't think he used the word dropped. So I don't 12 think you accurately characterized his testimony. 13 A. Consistent with that, I was 14 going to say I don't know if dropped is the right 15 word or not, but reconsidered within that time 16 frame, and because of that reason, that's my 17 understanding. 18 Q. The study was not done to the 19 best of your knowledge, correct? 20 A. That's correct. 21 Q. And the reason it was not done 22 was because of the results or the results of the 23 drug advisory committee meeting held in 1991 -- 24 A. My understanding was -- Page 348 1 MR. MYERS: Let her finish. 2 Q. The drug advisory committee 3 meeting held in 1991, correct? 4 A. That's correct, my 5 understanding was that as a result of that, the 6 study was not conducted. 7 Q. Who at Lilly made the decision 8 not to do the study after the 1991 advisory 9 committee meeting? 10 A. I don't know, ma'am, I'm 11 sorry. 12 Q. How about the FDA, who at FDA 13 decided that the study didn't need to be done, if 14 you know? 15 A. I don't know. 16 Q. Who would be in charge of 17 making such decisions at Lilly? 18 A. At that time? 19 Q. Yes. 20 A. I think Doctor Thompson was 21 senior clinical expert or clinical officer, if 22 you will. 23 MR. MYERS: While he's looking, on the 24 record I'm going to hand you a clean copy of the Page 349 1 document that you complained so vociferously 2 about yesterday. It's Pz 1063 1473 to 74. 3 MS. ZETTLER: Which redacted copy that 4 was marked as Exhibit -- 5 MR. MYERS: Five. 6 MS. ZETTLER: Exhibit 5 yesterday. 7 MR. MYERS: Right. 8 A. And by way of follow-up 9 business to yesterday, I promised that I would 10 give you the name of the office at FDA that 11 managed advisory committees, and surprisingly 12 enough, it's called the committee management 13 office. 14 Q. And that was the office that 15 you were referring to yesterday that was in 16 charge of approval -- 17 A. Right, and processing all the 18 advisory committee members, et cetera. 19 Q. You have got to let me finish 20 my question. 21 A. I'm sorry. 22 Q. The name of the office that 23 was in charge of the administrative end of the 24 approval process for advisory committee members Page 350 1 is what? 2 A. The committee management 3 office. 4 Q. And that would be where we 5 would go if we wanted to find all, for instance, 6 who nominated a certain committee member to the 7 committee? 8 A. Yes, ma'am. 9 Q. If you could turn back to 10 Exhibit 4. I asked you earlier who at Lilly 11 would have made the decision not to conduct a 12 rechallenge study after the 1991 advisory 13 committee meeting, and you said you did not 14 recall. Does looking at the list of people who 15 are recipients of this May 15th, 1991 memo 16 regarding a rechallenge protocol meeting held in 17 May of 1991 refresh your recollection as to who 18 would have made that decision? 19 A. No, not really. I think I 20 have said Doctor Thompson was the chief medical 21 person. Doctor Zerbe was second to him, and we 22 talked yesterday about the organizational 23 structure, I think, during this time frame. It 24 doesn't help any, other than that. Page 351 1 Q. Is Doctor Leigh Thompson 2 highest on the corporate food chain, so to speak, 3 on this list? 4 MR. BROWN: Whose food chain? 5 A. I will respond to your 6 question, but being something of a biologist I'm 7 not sure that food chain is appropriate. 8 MR. BROWN: Drug chain? 9 A. Yes, he is, he's most senior. 10 Q. Okay. 11 MR. BROWN: How do you spell Doctor 12 Zerbe? 13 MS. ZETTLER: Z-E-R-B-E. 14 A. Robert is the first name. 15 Q. When did Lilly start using the 16 Costart dictionary with regards to Fluoxetine? 17 A. I can't specifically state for 18 Fluoxetine, but I believe we started using 19 Costart almost from the beginning of our Drug 20 Experience Network system, that would be 1983. 21 Q. Are you familiar with the 22 ELECT dictionary? 23 A. Yes, ma'am. 24 Q. What is the ELECT dictionary? Page 352 1 A. ELECT dictionary was the Lilly 2 version of the Costart, in other words we called 3 it ELECT, but it was the FDA Costart dictionary. 4 Q. Was it identical in every way 5 to the Costart dictionary? 6 A. I think that it was. I think 7 we added some terms. One that strikes me was we 8 added surgical procedure, I believe, over Costart 9 because we would get spontaneous adverse event 10 reports of people who had undergone surgery, and 11 we had no way of collecting the terms so we added 12 that for ELECT. But the agency had problems with 13 that because they felt that if we were going to 14 use Costart for ninety-nine point nine nine 15 percent, we probably should use it for all of the 16 terms. 17 Q. Other than surgical procedure, 18 are you aware of any terms that are different, 19 either added or deleted from the ELECT dictionary 20 as opposed to the Costart dictionary? 21 A. No, ma'am, I'm not. 22 Q. Why did you call the 23 dictionary ELECT as opposed to just calling it 24 the Costart dictionary? Page 353 1 A. That's a very good question. 2 I think Doctor Thompson developed the acronym, 3 which was kind of catchy, Eli Lilly event 4 classification terms. 5 Q. Catchier than Costart? 6 A. Costart had already been used, 7 so we had to have something original. Honestly, 8 it just -- I don't know, I really don't know. 9 Q. Did Lilly represent to the 10 public or at least the medical and psychiatric 11 professions that ELECT was a dictionary separate 12 and apart from Costart? 13 A. I think that we -- in 14 describing ELECT, I think that we said that it 15 was based on and virtually identical to FDA's 16 Costart, I think we always had those linkages 17 there. So we didn't represent it as being 18 something that we ourselves came up with because 19 that would have been incorrect. It was based 20 primarily, with the one exception that I can 21 recall, exactly identical to Costart. 22 Q. Do you recall when the event 23 term suicide attempt was first put in the Costart 24 dictionary? Page 354 1 A. No, ma'am, I don't. 2 Q. How about accidental injury? 3 A. No, ma'am. 4 Q. How about the ELECT 5 dictionary, do you recall when accidental injury 6 was first added to the ELECT dictionary? 7 A. No, ma'am. 8 Q. You started working with 9 Fluoxetine in 1985? 10 A. Yes, ma'am. 11 Q. Was ELECT a dictionary that 12 was used just in the development of Fluoxetine or 13 was it used across the board in all 14 psychopharmacological drugs that were being 15 developed during that period of time at Lilly? 16 A. In fact I can answer to the 17 affirmative and broaden it. It was not only just 18 psychopharmacological drugs but all drugs from 19 that '85 period on that I was aware of. 20 Q. The ELECT dictionary? 21 A. No, I'm sorry, I misunderstood -- 22 well, ELECT, yes, ELECT to me equals Costart. 23 Q. Do you have any knowledge as 24 to which dictionary was provided to clinical Page 355 1 investigators at investigational sites at 2 clinical trials on Fluoxetine? 3 MR. MYERS: Before you answer, Doctor 4 Talbott, let me just caution you, I think Ms. 5 Zettler, and you correct me, is drawing the 6 distinction between the two dictionaries. So do 7 not equate them because I think she's drawing a 8 distinction. When she says ELECT, I think she 9 means ELECT -- 10 THE WITNESS: For the rules of the 11 road, then, okay, that's fair. 12 A. And could you give me a time 13 frame for that, your last question? 14 Q. Sure. Up until the time that 15 the firm officially switched from ELECT to using 16 Costart directly. 17 A. And the -- 18 Q. '85, say '85? 19 A. And I'm sorry, but the 20 antecedent to that then was -- now I know what 21 the time frame we're talking about, I want to 22 know what your question was. 23 Q. I want to know if the physical 24 dictionary that was given to the investigational Page 356 1 sites for human clinical trials was the Costart 2 dictionary in the form that it was put out by the 3 FDA or Lilly's version of the Costart dictionary, 4 ELECT? 5 A. Within that time frame, it was 6 ELECT. 7 Q. Do you recall when they 8 switched from ELECT to using FDA's formal 9 Costart? 10 A. No, ma'am, I don't. 11 Q. Do you know if it was before 12 or after 1990, beginning of 1990? 13 A. I wouldn't even hazard a guess 14 on that. My very faint recollection is it might 15 have been before, but take it with that caveat. 16 Q. Is it your understanding that 17 you can get an actual physical copy of the 18 Costart dictionary either in hard copy or on 19 computer disks from the FDA? 20 A. That we cannot? 21 Q. You can. 22 A. We can, yes, I thought we 23 could, yes. 24 Q. To your knowledge does the FDA Page 357 1 have any objection to a hard copy of the Costart 2 dictionary being copied and distributed to 3 clinical and investigational sites? 4 A. I don't believe I have seen 5 any prohibition against that. I'm not sure if 6 it's copyrighted or not, but I've never heard of 7 anything that would prohibit that. In fact, I'm 8 not sure if the agency has any prohibition on 9 publication of any of their documents. 10 Q. Are you familiar with the 11 format of the Costart dictionary? 12 A. Generally. 13 Q. Are you aware that there are a 14 number of different indexes, they call them, or 15 sections within the dictionary? 16 A. You just exceeded my level of 17 knowledge. No, ma'am, I wasn't aware of that. 18 Q. Are you aware that the Costart 19 dictionary has a section where it equates their 20 terms, their event terms with the World Health 21 Organization event terms or the WHOART 22 dictionary? 23 A. In other words something like 24 a translation between the two? Page 358 1 Q. Right. 2 A. Yes, I heard there was one of 3 those. I didn't know it was the agency's 4 document, though. 5 Q. Have you ever seen an ELECT 6 dictionary where that is done? 7 A. No, I can't recall. 8 Q. You don't recall either way or 9 you don't recall ever seeing one? 10 A. That's fair, I don't recall 11 either way. 12 Q. It you could look back in 13 Exhibit 1. Yesterday I believe it was your 14 testimony that the reason that Lilly would assign 15 the event term depression to the synonym suicidal 16 ideation is because that's the way it was done in 17 the Costart dictionary, correct? 18 A. That was, yes, ma'am. 19 Q. After Doctor Bouchy's memo 20 raised the issue of whether or not such 21 assignment was appropriate, to your knowledge did 22 anybody at Lilly approach the FDA about changing 23 the Costart terminology usage? 24 A. Let me answer that with the Page 359 1 condition that I'm not sure that Claude is -- I 2 think you're talking about whether this was his 3 position or not, so by answering your question, I 4 don't mean to confirm that he is a physician or a 5 doctor. But in answering your primary question, 6 no, I'm not aware of whether anybody did that or 7 not. 8 Q. So you don't know whether 9 anybody from Lilly has ever approached the FDA 10 about using the Costart event term of depression 11 to describe suicidal ideation, correct? 12 A. That's correct, ma'am. 13 MS. ZETTLER: As opposed to marking 14 this as an exhibit to the deposition, can we 15 refer to -- make a record of the Pz number? 16 MR. MYERS: Sure, that's fine. 17 Q. Doctor, we've been given a 18 copy of the ELECT dictionary, what purports to be 19 the ELECT dictionary, by Lilly. The Pz numbers 20 for our references that encompass this document 21 is Pz 2522 738 through Pz 2522 1125. And because 22 it's -- looks like it's almost three inches 23 thick, we're not going to mark it as an actual 24 exhibit to the deposition. Does that seem fair Page 360 1 to you? 2 A. If it's okay with Mister 3 Myers, that's fine with me. 4 MR. MYERS: Unless you want to mark it 5 and keep it, I don't care, it doesn't make any 6 difference, we know the numbers. 7 Q. One of the questions that 8 Doctor Bouchy had raised in his memo, that is 9 E-mail that's been marked as Exhibit 1, is 10 whether or not the use of the term overdose would 11 be ambiguous with regards to a suicide attempt, 12 correct? 13 A. Again, I'm not sure he's a 14 doctor or not. I don't mean to be picking on 15 that, okay. 16 Q. I'm sorry, he's been referred 17 to as a doctor in other depositions, and I'm just 18 used to using that. 19 A. I understand. And even if you 20 say it and if I answer without saying this again, 21 for time-saving sake, it doesn't mean that I 22 confirm that he is, or isn't, for that matter. 23 Q. That's fine. 24 A. Could you read back the Page 361 1 question? 2 Q. I'll just ask it again. 3 Doctor Bouchy has complained in this -- at least 4 in this memo, that he felt the term overdose was 5 not free from ambiguity as far as being used in 6 suicide attempt, right? 7 A. That's right, that's what he 8 says. 9 MR. MYERS: Let me belatedly object to 10 the form. I don't know that the word complain is 11 in the memo, so I don't know that you 12 characterized what he was doing or not. 13 MS. ZETTLER: Doctor Talbott seemed to 14 understand what I was saying. 15 A. The sentence that says the 16 term overdose is not free from ambiguity. 17 Q. He was also concerned about 18 using the term depression to describe suicidal 19 ideation, correct? 20 A. He comments on that, I think, 21 in that same paragraph we were just talking 22 about. 23 Q. In your opinion, is the use of 24 the word depression to describe suicidal ideation Page 362 1 in any way ambiguous? 2 MR. MYERS: Before he answers, let me 3 object to the form because that may call upon 4 this nonphysician to render some sort of opinion 5 testimony concerning clinical and medical 6 terminology, and I don't think he's qualified. 7 MR. BROWN: We'll join the objection. 8 MR. MYERS: If you know, Doctor 9 Talbott, go ahead and tell her if you're able to. 10 MR. BROWN: There's no proper -- he's 11 not been qualified as an expert to testify on any 12 medical issue. 13 A. That calls for more clinical 14 knowledge and expertise than I have to answer, 15 I'm sorry. 16 Q. What is your role with regards 17 to the reporting of adverse drug reaction reports 18 to the FDA with regards to Fluoxetine? 19 A. Well, with regards to 20 Fluoxetine and all of our drugs, the drug 21 epidemiology unit, which I may refer to as DEU, 22 as well, is the group that collects the adverse 23 event information on our products through the 24 system we called earlier, Drug Experience Network Page 363 1 or DEN, and then the drug epidemiology unit works 2 with our physicians to make the clinical 3 assignments for the adverse events, and then my 4 division ensures that these reports are submitted 5 not only to the FDA but to regulatory agencies 6 around the world. 7 Q. And when you say that making 8 clinical assignments to the adverse events, you 9 mean assigning event terms to the adverse events? 10 A. That's correct, ma'am. 11 Q. And my understanding is the 12 way the events are usually reported is either 13 through -- in the example of a clinical trial, 14 through the investigational site itself, either 15 filling out a section on a clinical report form 16 or phoning in depending on the severity of the 17 event, correct? 18 A. Right, and we were talking 19 about clinical trials there, right? 20 Q. Uh-huh. And that somebody 21 from Lilly -- at Lilly here, takes that 22 information and fills out what is commonly known 23 as a 1639 form that is submitted to the FDA 24 eventually, correct? Page 364 1 MR. MYERS: We're talking about this 2 clinical trial event again? 3 MS. ZETTLER: Right. 4 A. Let me add something to that, 5 there's actually another step in there. The 6 calls come in from the clinical investigator to 7 the paramedicals that are administering the 8 clinical trials, they fill out the forms and then 9 send those to the drug epidemiology unit. I 10 think you said -- at least someone might infer 11 that the clinical investigators call directly to 12 my drug epidemiology unit. 13 Q. Right, I'm sorry. And the 14 Costart or ELECT dictionary, depending on the 15 time period, are used to assign those event 16 terms, correct? 17 A. That's correct. 18 Q. Let's refer to the document 19 that we have described earlier that has been and 20 is titled drug and ELECT Eli Lilly classification 21 term dictionaries, okay? 22 A. Uh-huh. 23 Q. You have to say yes or no. 24 A. I'm sorry, yes. Page 365 1 Q. I want to get a general 2 understanding on how this dictionary is 3 structured. The first -- it looks to me like 4 it's broken down into three sections, okay? 5 A. Okay. 6 Q. The first section listing on 7 the left-hand column, the ELECT classification 8 term, and in the right-hand column, the ELECT 9 synonym term, correct? 10 A. That's what it says here. 11 What are we looking at, page one? 12 Q. Page one. And then you can 13 look through this, if you want, but the second 14 section, at least as far as my calculations are 15 concerned, seems to start at page Pz 2522 859, 16 and in this situation, it lists the ELECT synonym 17 term on the left-hand corner and the ELECT 18 classification term on the right -- I'm sorry, on 19 the left-hand side, and the ELECT classification 20 term on the right-hand side. So in other words, 21 the two columns are reversed, correct? 22 A. Exactly. That's the heading 23 here, and that also is listed as page one. In 24 fact, it might help to bring in the caption, it Page 366 1 says ELECT dictionary sorted by synonym term. 2 Q. And then the third section 3 appears to start at page Pz 2522 979, it's 4 entitled the drug dictionary sorted by synonym 5 term, correct? 6 A. That's correct. 7 Q. I'm not concerned with this 8 section, I'm not going to ask any questions about 9 this section, but if you want to look through 10 this, that's fine. 11 A. Give me just a second. 12 Q. Sure. 13 A. That also is a page one, drug 14 dictionary sorted by synonym term, two columns. 15 One is drug syn, S-Y-N, term. The second column 16 is headed drug code with, what is that, a 17 four-character code. 18 Q. So these are codes that have 19 been assigned by Lilly to various drugs that are 20 either manufactured by Lilly or used by Lilly in 21 clinical trials? 22 A. I don't know the origin of 23 that code. I know that there are some standard 24 codes from, I believe, the World Health Page 367 1 Organization that applies to drugs, so I'm not 2 sure, Ms. Zettler, whether that four-digit code 3 that we talked about is ours alone or from one of 4 these standard non-Lilly dictionaries. So at 5 least there's a four-digit code there. 6 Q. But the drugs listed in this 7 dictionary are drugs either manufactured or 8 tested by Lilly or used -- otherwise used in 9 clinical trials? 10 A. Give me a second because there 11 are a lot of them on here. 12 Q. Sure, take your time. 13 A. If I could -- you're right in 14 part, but actually there appear to be some other 15 drugs in here. 16 Q. Maybe I can clear it up real 17 quick. Other drugs that are listed in the drug 18 dictionary portion of the ELECT -- or the exhibit 19 are drugs that may have been used or related as 20 concomitant drugs or drugs that were taken listed 21 in the spontaneous report, for instance? 22 A. Yes, ma'am. That's because 23 there are some in here, I'm sure, A, that we 24 don't make, and B, for example we wouldn't be Page 368 1 studying, and let me give you an example. Alba, 2 A-L-B-A, Creme, here on page three, what is that, 3 L3BY4, I guess, is the drug code. So I know A, 4 we don't make that, and B, I don't think we would 5 be studying it. So it must show up some other 6 place then. 7 Q. Okay. 8 A. All right. 9 Q. Sure. Going back to the first 10 section, where the ELECT classification terms are 11 listed on the left and the synonym terms are 12 listed on the right. 13 A. Yes, ma'am. 14 Q. My understanding is the ELECT 15 classification term is the term to which the 16 synonym term would map, is that correct? 17 A. That's correct. I would say -- 18 map, I'm not sure. That may be -- someone who is 19 more familiar with the dictionary than I am, that 20 might be their term. But what I would say is the 21 ELECT classification term is the higher level 22 term, and then under that are subterms, which in 23 this case we call ELECT synonym terms that map to 24 that. So, for example, hunger pain and Page 369 1 epigastric pain, both would link to or be part of 2 abdomenal pain. 3 Q. Okay. When a clinical 4 investigator or somebody at Lilly would be using 5 this dictionary or even a Costart dictionary, 6 would it be fair to say that what they would do 7 is be to take the term that they have assigned or 8 somebody else has assigned to the event and then 9 see where it is linked to in the Costart 10 classification terms, in other words would they 11 be more likely to use the second half of the 12 dictionary as opposed to using the first? 13 MR. MYERS: Before he answers, let me 14 object to the form of the question because it may 15 call for him to speculate as to what some 16 clinical investigator would or would not do. 17 MS. ZETTLER: I'm asking him of his 18 understanding of the process. 19 A. In other words which direction 20 would it go? 21 Q. Sure. 22 A. In other words from 23 classification term to synonym term or vice 24 versa? Page 370 1 Q. Right. 2 A. I really don't know. It looks 3 like, on the basis of this, you could do it both 4 ways, whichever way suited you. Because if you 5 had a more general term, you might start with the 6 section that puts the more general terms on the 7 left-hand, or you might flip it around. I really 8 don't know, Ms. Zettler, I can't be of any help 9 on that, I'm sorry. 10 Q. Go back to the first section, 11 and referring again to Exhibit 1. 12 A. Okay. 13 Q. If we go to -- this is -- in 14 this first section of this dictionary, the ELECT 15 classification terms are listed alphabetically in 16 the left-hand column, correct? 17 A. Yes, appears to be so, right. 18 Q. So if we go down to the D 19 section, and we look under -- look up depression, 20 which falls on page twenty-nine of the first 21 section, correct? 22 A. Give me a second. Here's 23 depression right at the bottom of the left-hand 24 corner. I could even -- it's on -- the Pz number Page 371 1 is Pz 2522 767, which corresponds to page 2 twenty-nine of that section. Then in answer to 3 your question, yes, depression starts in the 4 left-hand column under like classification term 5 at the bottom of the page or so. 6 Q. And that in fact runs into the 7 first couple of inches of the second page too, 8 correct? 9 A. Right, and that page being 10 page seven sixty-eight. 11 Q. Doctor Bouchy, in Exhibit 1, 12 was concerned about assigning the term depression 13 to suicidal ideation, correct? 14 A. Yes, he maybe comments on it 15 there in, I believe, the second paragraph of his 16 note. 17 Q. This ELECT dictionary that 18 we've been looking at is dated January 16, 1990, 19 correct? 20 A. That's correct, upper 21 left-hand corner -- or, excuse me, upper 22 left-hand corner of each page, it looks like. 23 Q. Do you know if this was the 24 dictionary that was being used at the time of Page 372 1 Doctor Bouchy's E-Mail dated June 14, 1990? 2 A. No, ma'am, I'm sorry, I don't. 3 Q. Could you for me, I know it's 4 tedious, but could you for me count up the number 5 of synonyms that are linked to the ELECT term, 6 classification term depression in the January 16, 7 1990 version of the ELECT dictionary? 8 A. In other words you want me to 9 count the terms here in the ELECT synonym term 10 column, starting on page twenty-nine, that 11 relates then to the term depression over on the 12 left-hand column? 13 Q. Right. 14 A. Do you have a piece of paper -- 15 I'll just use one of these exhibits, Ms. Zettler. 16 Q. Oh, I see, I thought you were 17 going to write on it. 18 A. No. There appear to be 19 twenty-seven terms under the ELECT synonym term 20 column on page twenty-nine, and thirty, then, 21 that link to the ELECT classification term 22 depression in the left-hand column of those two 23 pages. 24 Q. Okay. And the right-hand Page 373 1 column of the page lists the synonyms, in other 2 words the terms or descriptions that would be 3 linked to or assigned to the ELECT classification 4 term depression, correct? 5 A. Yes. If you -- for example, 6 if you were to say reactive depression as an 7 ELECT synonym term, then it maps over then to 8 depression as an ELECT classification term on 9 this January of '90 version. 10 Q. Okay. And this dictionary 11 would be used by Lilly employees who were charged 12 with assigning event terms to adverse event 13 reports that would come in either through 14 clinical trials or through spontaneous reports, 15 correct? 16 A. Yes, that's correct. 17 Q. So if I were, say, a clinical 18 research associate that -- or administrator, I 19 believe it's clinical research administrator? 20 A. Administrator, yes, ma'am. 21 Q. Clinical research 22 administrator who was charged with reviewing 23 event reports that have come in, and somebody 24 reported to me that somebody had become -- had Page 374 1 suffered from suicidal thoughts, I would look up 2 suicidal thoughts in this dictionary, and I 3 would, as a result of the way the dictionary is 4 set up, assign the classification term depression 5 to that event term, correct? 6 A. To the portion of the adverse 7 event that asks for the, like, classification 8 term. But again, there are other areas where the 9 actual words from the investigator would be 10 reported as well. 11 Q. And that would be in the free 12 text section of the 1639? 13 A. Yes, I am not sure what the 14 exact term is, but there's a very large section 15 where you can write in comments, the exact words 16 of the investigator, et cetera. Free text is a 17 good term, although I'm not not sure that's 18 formally what it is called. 19 Q. Let's concentrate on just the 20 assignment of classification terms at this point, 21 as opposed to information on the other parts of 22 what ends up being filed with the FDA, being the 23 1639. 24 A. But understand, though, that Page 375 1 I'm not involved with assignment of these, I've 2 never, in my entire life, assigned an ELECT 3 synonym term to an ELECT classification term. 4 Q. Okay. 5 A. So it's a general 6 understanding, and you're helping me here, in 7 fact I've now seen more dictionary codes in the 8 last few minutes with you than I have in the 9 preceding twelve years that I have been with 10 Lilly. So with that understanding, I will be 11 glad to continue to answer. 12 Q. Fine. It's just to the best 13 of your understanding. As far as this -- and 14 when I say this copy of the dictionary is 15 concerned, can we generally agree that it's the 16 one dated January 16, 1990? 17 A. Yes, we don't have to keep 18 saying that, sure. 19 Q. Okay. As far as this version 20 of the dictionary is concerned, the ELECT synonym 21 terms, in other words the terms that would be 22 assigned by the originator of the report, for 23 instance -- 24 A. The investigator, for example, Page 376 1 sure. 2 Q. -- the investigator or maybe a 3 doctor from the outside who had -- 4 A. On a spontaneous, sure. 5 Q. Okay. Twenty-seven variations 6 of what may be assigned by the originator of the 7 report mapped to or linked to the classification 8 term depression, correct? 9 A. I think, yes. Now you asked 10 me to count, and twenty-seven, I think, I counted 11 correctly was the number. 12 Q. And we've gone through a 13 couple of them. One of them, we know, at least 14 at this time, was suicidal thoughts, correct? 15 A. I haven't gone through it with 16 you, but we are both looking at it right now, 17 yes, kind of at the bottom of page twenty-nine. 18 Q. Agitated depression is another 19 one, I think you brought up yourself earlier. 20 A. No, I think I said reactive 21 depression. 22 Q. I'm sorry, reactive 23 depression. But there are twenty-seven different 24 ones from plain depression, in and of itself, to Page 377 1 melancholia, to depressive reaction, to major 2 depression, to depressive neurosis, to bipolar 3 disorder, and a bunch of different things in 4 between, correct? 5 A. Those are terms that are 6 there, yes. Please don't ask me what they mean. 7 Q. Okay. How is somebody who is 8 looking at just the ELECT -- or, I'm sorry, the 9 1639, without reading the free text portion or 10 any of the comments sections, just looking at the 11 ELECT term depression that has been assigned in 12 and of itself, going to know if this person was 13 suffered from agitated depression or suicidal 14 thoughts or bipolar depression disorder? 15 MR. MYERS: Let me object to the form 16 of the question to the extent it assumes that 17 whoever would review such a form would only look 18 at that, and that would call on him to speculate 19 as to what some other person would or wouldn't do 20 in reviewing the forms. 21 Q. I'm limiting my question just 22 to if you were going to look at the terms 23 assigned to the events themselves, without 24 looking at the free text portion or any other Page 378 1 comment section of the 1639, how would a person 2 be able to differentiate what is meant by the 3 term depression between these twenty-seven 4 synonym terms? 5 MR. MYERS: I make the same objection 6 to the form. If you can answer, Doctor Talbott, 7 tell Ms. Zettler. 8 A. Maybe if I can ask a few 9 questions to clarify that, maybe we can answer, 10 okay? 11 Q. Sure. 12 A. There would be absolutely no 13 other information available to the person other 14 than the ELECT -- are we saying ELECT, yes, ELECT 15 classification term depression, that's what 16 you're saying? 17 Q. Right. I just want to know, 18 just given that there are twenty-seven synonym 19 terms that can be linked to the ELECT 20 classification term depression, I want to know 21 how, looking at just the classification term 22 itself, you can differentiate between these 23 twenty-seven synonyms? 24 A. Under the context that we Page 379 1 discussed there, were somebody to be that limited 2 in their information gathering, they would only 3 know it was depression, but of course under the 4 conditions we discussed, they wouldn't know what 5 the drug was, what the patient was, what the 6 outcome was or anything else. So in that, to me, 7 extraordinary hypothetical circumstance, it would 8 be depression is what they would see. 9 Q. And they wouldn't know from 10 looking at that whether or not the person was 11 suffering from suicidal thoughts or agitated 12 depression or any of the other twenty-seven 13 various synonym terms? 14 MR. MYERS: When you say looking at 15 that, you mean the ELECT classification terms? 16 MS. ZETTLER: Right, in and of itself. 17 MR. BROWN: You said wouldn't they, 18 that requires him to speculate. 19 A. Well, anybody that would be 20 looking at an ELECT term would realize that there 21 are subterms associated with that. So again, in 22 that very hypothetical narrow circumstance that 23 we described, which I can't imagine would happen, 24 they would know, even with that, that there were Page 380 1 potentially twenty-seven other terms that matched 2 to that. So if they just stopped with that one 3 word, it's depression. But anybody who would 4 know enough to look at that word, would know also 5 enough that there would be twenty-seven synonym 6 terms associated with it. 7 Q. Are you familiar with the FDA 8 spontaneous reporting system? 9 A. I know what it is. The degree 10 of familiarity, I'm not sure. 11 Q. Can you tell me what your 12 understanding of that system is? 13 A. It's a system that was 14 established by the FDA to collect spontaneous, 15 and in this instance spontaneous reports are 16 those reports that come from the use of products 17 in everyday medical uses. 18 Q. Okay. And what types of 19 information are reviewed to collect information 20 for that system? 21 A. It would be the reports that 22 come in from consumers, patients, any source. 23 Even attorneys, believe it or not, submit adverse 24 event reports to the FDA. Page 381 1 Q. Manufacturer? 2 A. Manufacturer, exactly, that's 3 what I was getting to. That sort of thing. So 4 the report that's submitted to the agency could 5 come from any of those sources, it could contain 6 the information that those sources put on the 7 report. And as you know, there's probably a form 8 that is used called the FD 1639 that asks for, I 9 believe, about fifty or fifty-five different 10 pieces of information. So those forms actually 11 are in wider use than one might expect because 12 the agency sends out, I believe, every quarter 13 something called the drug bulletin to physician 14 health care practitioners around the country, and 15 the last I heard that was upwards of five or six 16 hundred thousand people receive that mailing. 17 And every time one of those goes out, the very 18 last page is a form 1639. So health care 19 practitioners around the country, in addition to 20 clinical investigators, in addition to 21 manufacturers, have the form 1639s, and most 22 often that's the mechanism by which information 23 is put in the spontaneous system at the FDA. 24 Q. How long is the form, is it Page 382 1 one page, two pages? 2 A. It's a one-pager. We, on 3 occasion, expand it. 4 Q. In fact, you add comments that 5 may come up in one of, like, for instance, the 6 box twelve asks for any comments, and you may 7 have something that overflows box twelve, so 8 you'll connect box twelve -- the expansion into 9 box twelve to the one-page form? 10 A. Right. You've seen the forms 11 and seen examples, I'm sure. 12 Q. But the average doctor has 13 that one-page form to fill out? 14 A. That's correct. 15 Q. And -- 16 A. And, I'm sorry to interrupt, 17 you said has, almost like it is a requirement. I 18 didn't want to leave that impression. 19 Q. In fact there is no 20 requirement that doctors fill out 1639 forms and 21 submit them to the FDA when they see an adverse 22 event that somebody has on a product, correct? 23 A. That's my understanding. 24 Q. But there is a requirement Page 383 1 that if the manufacturer receives reports of 2 adverse events that they report them to the FDA, 3 correct? 4 A. That's correct. 5 Q. Isn't it true that the FDA 6 has, in fact, itself published or people that do 7 work for the FDA published papers that talk about 8 the percentage of adverse events that are 9 actually reported, regarding drugs in general, 10 not just Fluoxetine or any given drug? 11 A. I'm not sure I follow that. 12 Q. Haven't they done a 13 statistical analysis that has been reported to 14 show that only about ten percent of adverse 15 events that are actually occurring are actually 16 reported to the FDA? 17 A. I understand now, thank you. 18 I'm not sure that I've seen that report or I've 19 seen such a report. I have heard the number ten 20 percent bantered around, but I've never seen any 21 conclusive proof or any studies that would either 22 support or reject that number, percentage. 23 Q. Would you agree that only a 24 fraction of adverse events that actually occur Page 384 1 are reported to the FDA through whatever 2 mechanism? 3 MR. MYERS: Before he answers, let me 4 object to the form and the use of terminology, a 5 fraction. I think you can be a little more 6 specific. 7 MS. ZETTLER: He wasn't sure if he had 8 heard the actual percentage of ten percent. 9 Q. I'm just saying is it your 10 understanding that not all adverse events that 11 occur are actually reported to the FDA? 12 A. I'm sorry? 13 MR. MYERS: Go ahead. That's a 14 different question, go ahead and answer that. 15 A. I think that it would be 16 impossible to say that every adverse event report 17 that occurred was reported to the FDA. So in 18 answer to your question, you would be correct. 19 Q. Do you have an opinion as to 20 the percentages of adverse events that occur, 21 what percentage is actually reported to the FDA? 22 A. No, ma'am, I don't. Like I 23 said, I've heard the ten percent number, I don't 24 recall ever seeing an article or study that Page 385 1 confirmed that as being too high or too low. So 2 I have not formed an opinion. 3 Q. Have you ever seen a printout 4 from the FDA's SRS system, spontaneous reporting 5 system? 6 A. I believe that I have, yes. 7 Q. And what types of things are 8 listed in such a printout with regards to one 9 adverse event, say? 10 A. You know, it's been so long, I 11 really don't know. There's -- and I just have a 12 visual recollection of this now, and if I may, 13 I'll describe that to you. There's what appears 14 to be about an inch worth of information 15 horizontally across the page for each of the 16 reports, and what would be in that, I would 17 assume demographics, the outcome, any commentary 18 that the reporter or reporters had made, Costart 19 term or terms, probably. But again, this is just -- 20 this is really a very visual recollection of an 21 assumption of what might be contained in such, 22 I'm not sure -- well, those printout are 23 available, as you know, and those could show 24 exactly what's in there. Page 386 1 Q. Do you have a specific 2 recollection of the commentary or the report 3 being included in such a printout? 4 A. I seem to. I think it was -- 5 like we use the term free text a little earlier. 6 Q. Right. 7 A. It seems to me there was 8 something like free text in there. 9 Q. In the actual printout? 10 A. I think so. If you can show 11 me one, we can either show whether my memory is 12 correct or not. 13 Q. Let me ask you this: If in 14 fact the commentary section was not contained or 15 printed out with the other information that you 16 described in your recollection of the spontaneous 17 reporting system, would such a printout be useful 18 in determining, for instance, how many people 19 were suffering from suicidal ideation on 20 Fluoxetine? 21 MR. MYERS: Let me object to the form 22 of the question to the extent it calls on him to 23 form some medical clinical judgment on what a 24 hypothetical report would show, and I don't think Page 387 1 he's qualified. I think it would also be 2 somewhat speculative. 3 Q. Let me ask it this way: 4 Earlier you stated that you agreed, I believe, 5 that if all you had to look at were the event 6 terms that had been assigned to a particular 7 adverse event, but just looking at that event 8 term, you couldn't tell at least in the situation 9 of depression, which of those twenty-seven 10 synonyms were being related or mapped to that 11 classification term, correct? 12 A. Right. We had a hypothetical -- 13 just to confirm our understanding, we had a 14 hypothetical where we had only, I believe it was 15 called, the ELECT classification term, one word, 16 reported, and that's correct. And the only 17 possible add-on to that would be that anybody who 18 would look at that would be familiar either with 19 the ELECT or Costart, which are essentially the 20 same. But understand that there are then synonym 21 terms that map to that. He or she may or may not 22 understand or remember all of those -- did we say 23 twenty-seven? 24 Q. Right. Page 388 1 A. In this case, twenty-seven 2 synonym terms. 3 Q. Aren't you assuming that 4 anybody who would look at that would have an 5 understanding of Costart or ELECT or even know 6 that they exist? 7 A. Well, we had a hypothetical, 8 so I thought as long as we were making 9 assumptions, we might as well add that. 10 Q. But is it your belief or your 11 opinion that anybody who would look at a 1639 12 would know that the event terms that are assigned 13 are ones that are gleaned from either an ELECT 14 dictionary or Costart dictionary? 15 A. I would think so, wouldn't 16 you? 17 Q. No. 18 A. Well, we disagree. 19 Q. Would you agree with me that 20 John Q. Public could make a FOIA request to the 21 FDA and get 1639s that list the event term 22 depression for that -- for a particular drug, say 23 Fluoxetine? 24 MR. MYERS: Wait a second. You mean Page 389 1 somebody could do a FOIA request and get a bunch 2 of 1639s? 3 MS. ZETTLER: Right. 4 MR. MYERS: Could that happen? 5 A. You mean by FOIA, Freedom of 6 Information Act? 7 Q. Right. 8 A. Okay. And the question was 9 could John Q. Public make a FOIA request and get 10 1639s for depression? 11 Q. Let me ask it this way: Can 12 I, as an individual, a nongovernmental employee, 13 a nonmanufacturer employee, make a Freedom of 14 Information Act request to the FDA and get copies 15 of 1639s that list the classification term 16 depression? 17 A. Get the actual 1639 itself? 18 I'm not sure, Ms. Zettler, I've never done that, 19 so I really don't know. 20 Q. If that were possible, would 21 you expect the person, the average citizen to 22 have an understanding or a knowledge of the 23 existence of the ELECT dictionary and the Costart 24 dictionary? Page 390 1 MR. MYERS: Before he answers the 2 question, let me object to the form. That's 3 highly speculative for him to assess what such a 4 person making that kind of request would or would 5 not be aware of in making such a request, it 6 would be speculation. 7 MS. ZETTLER: He's already testified 8 fairly confidently that only people who would 9 understand or know that the Costart or ELECT 10 dictionary existed would be the ones reviewing 11 the 1639s. 12 MR. MYERS: To the extent you're 13 trying to recount his testimony, I don't think 14 that's accurate, and I think that was in response 15 to a separate hypothetical question that you 16 initially asked on this subject. 17 Q. Do you understand my question, 18 Doctor? 19 A. I would like to try to answer. 20 Q. Sure. 21 A. We're now assuming, because I 22 don't know, I remember I said I'm not sure 23 whether the 1639s are available, but if John 24 Q. Public made a request, and if the agency Page 391 1 allowed the 1639s to go out, and he or she 2 requested for depression, they would get the 3 1639, which if it came from Eli Lilly and 4 Company, would contain not only the ELECT term or 5 terms, but would also have free text, 6 supplementary commentary, et cetera, in addition 7 to the demographics, et cetera, that we talked 8 about. So if they looked specifically at the 9 term depression, it would mean to them probably 10 what depression means to them, but if they took 11 the time then to read the 1639 -- the time then 12 to request the 1639, and I assume -- since we're 13 assuming and hypothesizing here, I assume they 14 would read the whole thing, they at least, from 15 reports from Lilly, they would see the free text 16 or summary comments that would talk about these 17 terms, synonym terms, that contributed to the 18 ELECT term. That was tortuous, I'm sorry, but I 19 tried to at least answer your question. 20 Q. Doctor, let me tell you, we 21 have made a Freedom of Information Act request to 22 the FDA for all adverse events reported to the 23 spontaneous reporting system for Prozac since the 24 beginning of the testing of Prozac, okay. And we Page 392 1 have gotten twelve computer disks full of 2 information on various aspects of the individual 3 report, okay? 4 A. Sure. 5 Q. And, so, we have one report of 6 an adverse event. And what it turned out to be 7 is you had to take information from twelve 8 different disks and somehow merge it and 9 make sure you had everything involved. Not 10 anywhere on any of those disks are any reports of 11 any comments by any reporters, it's simply not 12 one of the elements that are reported at least on 13 the computerized printout, okay. If you accept 14 my explanation or what I just told you, do you 15 feel that if somebody were to look at that 16 printout, without the benefit of having an ELECT 17 or Costart dictionary in front of them, even if 18 they had the knowledge that they exist or have 19 used them, are they going to be able to tell from 20 that printout if the ELECT term or the Costart 21 term depression is suicidal ideation as opposed 22 to one of the other twenty-seven synonym terms 23 that have been related to depression? 24 MR. MYERS: Wait a minute, before he Page 393 1 answers, let me object to the form. I'm familiar 2 with the set of data you speak, and I don't know 3 that you precisely recited its format, so your 4 question is incomplete and not factual. Your 5 factual recitation is not correct. Additionally, 6 again it would call for him to speculate as to 7 what the reviewing person would or would not be 8 aware of in reviewing the data that you have 9 outlined to him. But if you're able to answer 10 the question -- 11 Q. All I'm asking you is if you 12 accept my recitation of what -- okay, that there 13 is no -- that there's demographic data, that 14 there are Costart terms that are assigned, that 15 there are dates of onset, there are dates of 16 reporting of the event to the FDA, there are 17 manufacturing of control numbers assigned by 18 Lilly, there are control numbers assigned by the 19 FDA, but nowhere, nowhere in any of those disks 20 that we have received is there any information 21 related in any way to any comments by reporters 22 or free text. So if you accept that as true, is 23 there any way from the information or just pure 24 assignment of that phrase depression, that ELECT Page 394 1 term depression, is there any way from that 2 information would we be able to tell what synonym 3 was mapped to depression out of those 4 twenty-seven? 5 MR. MYERS: Same objection. If you're 6 able to answer the question -- 7 A. I'm really not comfortable 8 answering it because the information that I 9 recall, and if we had the printout here, I could 10 even address it better, but the information that 11 I recall, as you remember in my testimony maybe 12 fifteen or twenty minutes ago, was that there was 13 something in addition to that very formal 14 information. And so with that recollection -- 15 and it's not that I don't believe you or that I'm 16 impugning your honesty at all, please, I wouldn't 17 do that, but I just don't feel comfortable 18 answering that question with that recollection 19 that I have. Had I not had that recollection, 20 then perhaps we could continue a discussion on 21 that. I'm sorry. 22 Q. Has Lilly ever used the word 23 suicide or the term suicide attempt to describe 24 an actual suicide attempt by somebody on Page 395 1 Fluoxetine? 2 A. I don't know, ma'am. 3 MS. ZETTLER: Do you want to take a 4 quick break? 5 THE WITNESS: Would you mind? 6 (A SHORT RECESS WAS TAKEN.) 7 Q. Outside the fact that 8 manufacturers are required by the FDA to report 9 adverse events that they become aware of on any 10 particular drug, not just on Prozac, do you have 11 an understanding of reporting requirements 12 related to say how fast they have to be reported 13 to the FDA by the manufacturer or in what form 14 they have to come in, et cetera? 15 A. Yes, I do. 16 Q. Can you tell me what your 17 understanding is? 18 A. Now are we talking about 19 spontaneous adverse events? 20 Q. Yes, we'll take spontaneous 21 adverse events. 22 A. Okay. And the portion of the 23 regulations that pertains to spontaneous adverse 24 event reporting, for our reference purposes, is Page 396 1 21 CFR, Part 314.80, eight zero. And under that, 2 then, the provisions are for really two time 3 frames for reporting adverse events. The first 4 time frame is for something called an alert 5 report, which is a report that is judged to be 6 serious and unexpected, and within fifteen days 7 of a manufacturer getting information indicating 8 that the adverse event is serious and unexpected, 9 the sponsor, the manufacturer, is to report this 10 event to the agency using the form 1639. That's 11 since changed now, and it's something called a 12 med watch form, which is very similar to the 13 original 1639 that was used all during the '80s 14 and '90s, the period we were talking about. I 15 said fifteen days, I'm not sure if I said fifteen 16 working days or calendar days, but it's my 17 understanding that it's fifteen working days. So 18 those are serious and unexpected adverse events 19 generated spontaneously from the market place. 20 Then all other or non-alert 21 events are reported by the sponsor in a periodic 22 adverse event report to the agency. Ms. Zettler 23 and I already talked a little bit earlier about 24 these reports which for the first three years of Page 397 1 a new drug's life were made on a quarterly basis, 2 and thereafter these are made on an annual basis. 3 Q. Okay. In fact Lilly files 4 1639 reports for adverse events that are not 5 determined serious and unexpected also, correct? 6 A. That's correct. 7 Q. But they do not file within 8 fifteen days necessarily? 9 A. Again, as those things that 10 are reportable within fifteen days, the alert 11 reports are those considered serious and 12 unexpected. 13 Q. I'm talking about non-serious 14 unexpected reports, okay, the non-alert -- 15 A. Non-alert okay. If we can use 16 that term, that would be helpful. 17 Q. Okay. Non-alert reports, 18 Lilly has maintained that they still file 1639s 19 or at least what was 1639 reports on each of 20 those events? 21 A. That was my understanding, 22 yes, ma'am. 23 Q. So it's your testimony or your 24 understanding that 1639s are filed with the FDA Page 398 1 on all adverse events that Lilly becomes aware 2 of, the timing of when they're filed depends on 3 whether or not the event is considered serious 4 and unexpected? 5 MR. MYERS: Spontaneous reports. 6 MS. ZETTLER: Spontaneous. 7 A. And if we can use alert versus 8 non-alert, that would be helpful for me too, in 9 other words non-alert. Now the only exception to 10 this is, and we for many years filed 1639s on 11 every non-alert report obtained, but the agency 12 specifically asked manufacturers, I believe, 13 about two years ago that for spontaneous 14 non-alert reports originating outside the United 15 States, that these should be described in a 16 tabular form rather than submit the actual 1639 17 copy or the more recent med alert copy. 18 Q. Okay. What's a med alert 19 form? 20 A. It's -- Commissioner Kessler, 21 I guess probably about this time last year, 22 announced a new program at the agency to 23 hopefully stimulate additional reporting of 24 adverse events by health care practitioners, and Page 399 1 it was put under the program heading of med alert 2 program. And consistent with that, then they 3 redesigned the form 1639 into the med alert form. 4 Now it has a number assigned to it, I think that 5 number is FD 2500, but understand I think that's 6 the number, we just referred to it as med alert 7 as opposed to 1639. It's just essentially the 8 1639 that's been redesigned. The same elements 9 of information are there, they're just placed at 10 different portions on the form. 11 Q. As far as the information that 12 the form is seeking, have there been any changes 13 in the type of information that the form seeks? 14 A. I will be have honest with 15 you, Ms. Zettler, I have not put a 1639 down next 16 to a med alert and gone point for point, but it's 17 my understanding they're exactly the same. 18 Q. Okay. I want to make sure 19 your testimony is clear because I think there was 20 like a miscommunication. What I'm just asking is 21 is it your understanding that Lilly files a 1639 -- 22 regardless of spontaneous reports, that Lilly 23 files a 1639 for each and every adverse event it 24 becomes aware of regardless of whether or not Page 400 1 it's an alert or non-alert report? 2 A. That's true with the exception 3 of the agency specifically asks manufacturers not 4 to submit 1639s on foreign non-alert reports, and 5 we complied. Up until that time, we had done 6 exactly as you said, and now per the FDA 7 directions we report those on a tabular basis. 8 Q. Do you have an understanding 9 as to whether or not adverse events that are 10 reported by means other than 1639s end up in the 11 FDA's spontaneous reporting system? 12 A. Okay. Let me see if I 13 understand your question, hypothetical, okay. 14 I'm John Q. Public citizen, I have an adverse 15 event or a reaction at the same time I'm taking a 16 drug, so I write FDA and say I'm taking this 17 drug, I have this reaction, would that 18 information then find itself into the FDA system. 19 My understanding is yes, it would. 20 Q. Outside that, where John 21 Q. Public wouldn't necessarily know the existence 22 of a 1639 or have access to a 1639, I'm talking 23 about in situations that you just talked about 24 where the adverse events reported from outside Page 401 1 the United States are tabulated as opposed to 2 being submitted in the 1639 form -- 3 A. Right. 4 Q. -- would those tabulated 5 adverse events make it into the spontaneous 6 reporting system as far as you know? 7 A. As far as I know, they would, 8 yes, ma'am. 9 Q. In the tabulations are you 10 asked to give specific information about each 11 adverse event similar to what's requested in the 12 1639? 13 A. Yes, ma'am. 14 Q. So really it's just instead of 15 having a lot more paper, it's just a tabulation? 16 A. That's right. 17 Q. And each individual adverse 18 event is described separately? 19 A. Yes, ma'am. 20 Q. And all demographic data is 21 given? 22 A. To my understanding. I don't 23 have one of front of me now, so I'm limited to my 24 recollection, but that's my understanding. Page 402 1 Q. And free text is given? 2 A. Again, a visual picture, as we 3 just discussed before the break, the visual 4 picture is that free text like information is 5 there. If we had some forms, I would be glad to 6 respond to those, but that's my recollection. 7 Q. Are those tabulations 8 submitted with safety updates? 9 A. By safety update, do you mean 10 just post-approval safety reports? Yes, in fact 11 those are part of the post-approval safety 12 reports. 13 Q. To your knowledge has Lilly 14 submitted such tabulations independent of 15 post-approval safety reports? 16 A. I really don't recall any 17 situations, I don't know, I really don't know. 18 Q. As far as an alert report is 19 concerned, the definition of serious and 20 unexpected is a regulatory definition, is it not? 21 A. Yes, in fact it's a verbatim 22 in the regs themselves, regulations themselves, 23 I'm sorry. 24 Q. Whether or not an event is Page 403 1 considered serious and unexpected is dependent 2 upon the outcome of the event, true? 3 MR. MYERS: Excuse me. You said 4 serious and unexpected? 5 MS. ZETTLER: Uh-huh. 6 MR. MYERS: I object to the form then. 7 A. I might be able to help you 8 out. I think that outcome determines seriousness 9 or not seriousness, outcome I don't think 10 impacted expected versus unexpected. 11 Q. Okay. And as far as 12 seriousness is concerned, there are four or five 13 outcomes that have been assigned by the 14 regulations that -- under which the event would 15 be considered serious? 16 A. That's correct, and we 17 originally talked about part 21 CFR 314.80, I 18 believe, is where they're listed as a subpart of 19 that. 20 Q. And those include death, 21 hospitalizations, administration of prescription 22 drugs, overdose, and congenital anomaly? 23 A. Uh-huh. 24 Q. And I believe cancer? Page 404 1 A. I believe you're right. I 2 would correct you on one item, though. The 3 agency modified in 1987 the criteria for 4 administration of prescription drug. That for a 5 while, you're absolutely correct, in '85 and '86, 6 and a portion of '87, that was one of the 7 criteria for seriousness as an outcome, but they 8 amended that and struck that in 1987 as one of 9 the criteria, so I believe there are only five 10 now, and you have the rest of them. 11 Q. But overdose is an outcome 12 that's considered serious under the regulations, 13 correct? 14 A. Serious with -- my 15 understanding -- because if -- I don't know if 16 you had a chance to read the wording lately or 17 not, but it's rather tortuously worded. My 18 understanding is if the overdose in any way 19 results in an event, whether that event is 20 serious or not is immaterial. If an overdose 21 results in an event, no matter how minor, that's 22 considered a serious event, I mean the overall 23 construct of it is. 24 Q. If you have a suicide attempt Page 405 1 as an event, and that suicide attempt results in 2 an overdose, then under the regulations that 3 suicide attempt would be considered serious, 4 would it not? 5 A. My understanding is that if 6 there were no events other than the fact that a 7 person took an overdose, in other words if there 8 were no sequela or signs or symptoms subsequent 9 to that overdose, my understanding is that that 10 would not be a serious event per se. 11 Q. And when -- was this true 12 since you've been involved with Fluoxetine? 13 A. Coincidentally, 1985 is when 14 the NDA regulations were rewritten and the 15 criteria that we were talking about were listed, 16 and so -- also coincidentally, you know, that in 17 1985 is when I became the regulatory scientist 18 for Prozac. So because of those two 19 coincidences, what you said is correct. 20 Q. So your understanding of 21 whether or not an overdose or suicide attempt 22 that results from an overdose is to be considered 23 serious was established in 1985, around the same 24 time that you became involved in Fluoxetine? Page 406 1 A. Yes. 2 Q. What determines whether an 3 adverse event is considered unexpected? 4 A. The appearance of the term in 5 the labeling -- or, excuse me, the package insert 6 for the product. We're continuing to talk about 7 spontaneous, and I will make that assumption 8 unless you tell me we're talking about a trial. 9 Q. That's fine. 10 A. Just to save ourselves some 11 time. If it appears in the package insert, then 12 it's considered an expected event. Unless, and 13 there's a provision in the regulations, I think 14 the -- this is not a direct quote, but it's an 15 approximation, the severity of the adverse event 16 is greater than what might otherwise be expected. 17 So it's not just a determination on yes, no, is 18 it in the package insert, there's also a proviso 19 that it might be in the package insert, but might 20 be of such an unexpected severity, if we will, 21 that it would then render it as being unexpected. 22 Q. So like a rash that is much 23 more severe than what had been previously 24 reported in the package insert? Page 407 1 A. Sure. 2 Q. Where in the package insert 3 does an event have to appear for it to become 4 unexpected? 5 A. It's my understanding that 6 anyplace in the package insert itself is 7 considered a label because the agency deems the 8 package insert to be part of the labeling, a 9 labeled adverse event. 10 Q. So, for instance, if suicide 11 attempt is discussed anywhere in the package 12 insert, it then becomes expected unless the 13 severity of the suicide attempt increases? 14 A. That's a fair 15 characterization, yes. 16 Q. Same thing with overdose? 17 A. I think it would apply to any 18 adverse event. 19 Q. How about if you have 20 overdoses where people did not die, and then all 21 of a sudden you had overdoses where people 22 started dying, would that be an increase in 23 severity that would render the event unexpected? 24 A. Interesting question. It will Page 408 1 be serious by virtue of -- let me walk through 2 the process. It would be serious by virtue of 3 the outcome, two ways. We talked about death, I 4 think, with the hypothetical. So it would be 5 serious by virtue of death, it would be serious 6 by virtue of an overdose which resulted in an 7 adverse event. So there, at least, were two 8 criteria for seriousness. Now the question was 9 an overdose that resulted in death could possibly 10 be increased severity unless there would have 11 been some allusion to the fact or some statement 12 to the fact that overdose could result in death. 13 Q. Is death considered an event 14 in that situation? 15 A. Personal opinion or 16 professional opinion? Personal, yes. But 17 interestingly enough, the agency says that no, 18 death is not an event, they say it's an outcome. 19 Q. What about a death that 20 doesn't have an explanation? 21 A. Okay. 22 MR. MYERS: Is that an event or an 23 outcome? 24 Q. Right, is it an event? Page 409 1 A. I'm sorry, I missed -- 2 Q. Say you have somebody who -- 3 say you had a person who was being administered 4 Fluoxetine and they found them dead and they had 5 no explanation to how they died or why they died? 6 A. So all we would have would be -- 7 let me continue this. All we would have would be 8 patient identity, some coded or blanked out, some 9 demographics possibly, on observed death with no 10 additional information, and Prozac as our pieces 11 of information, correct? 12 Q. Right. 13 A. Okay. Now, the question is -- 14 Q. Would that death be reported 15 as an outcome or would it be reported as an 16 event? 17 A. We would probably report it 18 both ways because we voluntarily, in the case of 19 all spontaneous events for all drugs, not just 20 Prozac, anytime we have a death we treat that as 21 an alert report regardless of whether we think 22 it's serious, not serious, expected or 23 unexpected. So our reporting would be to treat 24 it as an alert report. Now what would I call Page 410 1 that if I were asked? I would probably treat 2 death in that instance as an event, and I would 3 also treat it as an outcome, I would do it both 4 ways, I think, although the agency would quarrel 5 with me about calling death an event. 6 Q. How about overdoses, do you 7 voluntarily or does Lilly voluntarily treat all 8 overdoses as an alert report, alert event? 9 A. Again, for spontaneous, I'm 10 not sure that we do, I'm not sure that we do. If 11 it's a death, we would, certainly, but absent 12 that, if there were no other unexpected aspects, 13 I'm not sure that we would. 14 Q. And the problem with reporting 15 death, at least as far as your understanding, you 16 said the FDA would quarrel with you reporting it 17 as an event and outcome would be why? 18 A. I don't know, I think that 19 because they had -- going back to the '85 20 regulations that we talked about earlier for the 21 criteria for seriousness, I think that they want 22 to treat death solely as an outcome just for 23 definitional purposes. Again, that's speculation 24 on my part. And I think overdose as well. Page 411 1 Q. They want to treat that only 2 as an outcome as opposed to -- 3 A. As an event, yes. But again, 4 you're asking me and I'm not an agency person. 5 Q. In Exhibit 1, Claude Bouchy 6 speaks of assigning the event term overdose to a 7 suicide attempt. Wouldn't that, in effect, be 8 treating an overdose as an outcome as well as an 9 event? 10 A. Can you direct me to where? 11 Q. Sure. At the beginning he 12 says our point is the following, second 13 paragraph, physician has reported a suicide 14 attempt, do we have a right to change it to some 15 terminology which we may consider to be more 16 specific, EG overdose, which is not free from 17 ambiguity, okay. So at least he's discussing 18 changing the physician's reported event term of 19 suicide attempt to overdose. My question is, in 20 that case, wouldn't you have to list an overdose 21 as an outcome also? 22 A. If he were to change -- let me 23 follow here for a second. If he were to change a 24 suicide attempt to the ELECT term of overdose, Page 412 1 would you then have to report that as an outcome? 2 Q. If you list overdose as an 3 event, under the regulations wouldn't you have to 4 also list it as an outcome? 5 A. If you listed it as event, 6 wouldn't you have to list it as an outcome, 7 overdose outcome. Assuming -- again, remember 8 earlier we said that the agency has directed that 9 if it's an overdose without signs, symptoms, 10 sequela events, it's not reportable as an alert 11 report. You're talking here about an overdose, 12 we're assuming some signs, symptoms, sequela, et 13 cetera, wouldn't you then treat that as an 14 outcome, I think you probably would under those 15 conditions. 16 Q. So in this case you would have 17 an event term of an overdose resulting in an 18 overdose? 19 A. That's about the way it would 20 come out, yes. 21 Q. Would the FDA have a quarrel 22 listing overdose as an event term and as an 23 outcome like it would with death? 24 A. Again, we're speculating on Page 413 1 the agency's -- 2 MR. MYERS: Let me caution you, Doctor 3 Talbott, don't speculate. If you have a 4 reasonable basis to give an answer, by all means, 5 do it, but don't speculate. 6 A. The reason I was able to 7 comment the way I was about death is that the 8 agency actually has at some of the Food and Drug 9 law institute courses, and other things this 10 industry and physicians attended, actually 11 commented on their concern about that, and I 12 don't believe, Ms. Zettler, I've ever heard about 13 them, in parallel to that same discussion, talk 14 about an overdose. So I probably better not 15 speculate on that because I don't have a basis. 16 Q. Is there any regulatory 17 prohibition as far as you know of assigning an 18 event term that's outside of the Costart 19 dictionary? 20 A. Prohibition written in the 21 regulations? 22 A. Right. 23 A. Not that I'm aware of, no. 24 Q. So in effect, in this case Page 414 1 that's illustrated by Claude Bouchy in Exhibit 1, 2 the event term that was reported by a physician 3 as suicide attempt, could in fact have been 4 listed under the 1639 for this report as suicide 5 attempt with the outcome of overdose, correct? 6 MR. MYERS: Wait a minute, let me 7 object to the form and ask when you say listed in 8 the 1639, listed where and as what? 9 MS. ZETTLER: The Costart term or as 10 the event term. 11 MR. MYERS: Okay. 12 A. Okay. And just keeping with 13 the line of discussion we've had, I can't think 14 of any regulation in the United States that would 15 prohibit that. 16 Q. Okay. Referring you back to 17 the ELECT -- drug and ELECT dictionary that has 18 been provided to us by Lilly, the one that's 19 dated January of 1990, in the first section of 20 the dictionary, the section that we discussed 21 earlier, which lists the dictionary sort of by 22 classification term, in other words the ELECT 23 classification term is listed on the left-hand 24 side and the synonyms are listed on the Page 415 1 right-hand side, do you see that? 2 A. Yes, ma'am. 3 Q. On the left-hand side on page 4 one oh two, which correspondingly has the Pz 5 number 2522 840, there are -- the classification 6 term suicide attempt is listed five times, 7 correct? 8 A. That's correct, ma'am, the 9 classification term may be about a third of the 10 way down the page. 11 Q. And on the right-hand side, 12 lists suicide being one of the synonym terms that 13 relates to suicide attempt, suicide gesture, 14 suicide attempt, suicide attempt, no drug used, 15 and suicide - no drug involved, as synonyms, 16 correct? 17 A. That's correct, there were, 18 what, five synonyms there for suicide attempt. 19 Q. And this, in fact -- the 20 synonyms differentiate between a suicide attempt 21 straight out and a suicide attempt that was not 22 using a drug, correct? 23 A. Well, let's see. There's 24 suicide which links to suicide attempt as a Page 416 1 classification term, there's a suicide gesture as 2 a synonym which links to, again, suicide attempt 3 as a classification term, there's suicide attempt 4 as a synonym that links to suicide attempt as a 5 classification term, suicide attempt, comma, no 6 drug used, which links to suicide attempt 7 classification term, and then lastly, suicide, 8 hyphen, no drug involved, which links to suicide 9 attempt ELECT classification term. 10 Q. So suicide attempt, at least 11 as discussed by Doctor Claude Bouchy in Exhibit 12 1, would, if you were to look at it from the 13 standpoint of the ELECT dictionary that was in 14 existence in January of 1990, could map at least 15 to this dictionary to suicide attempt, could it 16 not? 17 A. That's correct, ma'am. 18 Q. Okay. On page eighty-one of 19 the same section of the dictionary provided to us 20 by Lilly, corresponding with Pz 2522 819, there 21 are three ELECT classification terms of overdose 22 listed in the left-hand margin, correct? 23 A. That's correct, maybe about a 24 third of the way down again. Page 417 1 Q. And the synonyms that map to 2 each of those overdose ELECT classifications are 3 overdose itself, drug overdose, and toxicity, 4 comma, drug, correct? 5 A. That's correct, Ms. Zettler, 6 there are as synonym terms, I don't know if you 7 mentioned that or not. 8 Q. At least as far as this copy 9 of the ELECT dictionary is concerned, this does 10 not map the synonym of suicide attempt to 11 overdose, does it? 12 A. No. We just saw, and I forget 13 the page number, but it was just in a preceding 14 discussion, a suicide attempt mapped to suicide 15 attempt as a classification term here, and per 16 your current question, overdose here as a synonym 17 term maps to overdose as a classification term. 18 A. So at least in this dictionary 19 as it relates to the classification term of 20 overdose, the synonyms listed do not include 21 suicide attempt, correct? 22 A. Not in the three we're looking 23 at, no, ma'am. 24 Q. It also doesn't list Page 418 1 intentional overdose, does it? 2 A. Not at least here, it doesn't. 3 Q. Are you familiar with the term 4 aggression cluster of events? 5 A. Aggression cluster? 6 Q. Of events. 7 A. Of events, no, ma'am. 8 (PLAINTIFFS' EXHIBIT NO. 8 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. If you could review Exhibit 8. 12 A. Thank you. 13 (DISCUSSION OFF THE RECORD.) 14 Q. Okay. Have you had a chance 15 to review Exhibit 8? 16 A. Yes, ma'am. 17 Q. This was the order that was 18 produced to us, and I realize that the fax 19 transmission doesn't necessarily correspond with 20 the other two pages, okay? 21 A. Yes, I noticed that. In fact, 22 I'm not sure -- I'm not sure if they are linked 23 or not other than by the staple in the upper 24 left-hand corner. Page 419 1 Q. Okay. As far as the first 2 page of the exhibit is concerned -- 3 A. Yes, ma'am. 4 Q. -- the fax transmission to 5 Tony DeCicco? 6 A. Yes, Mister DeCicco, if I may. 7 Q. Decicco. And he's with the 8 Food and Drug Administration, correct? 9 A. That's correct. 10 Q. And it's a fax transmission 11 that you made to him? 12 A. That's correct. 13 Q. Would the information that was 14 attached to this fax also be submitted to the 15 document control office at the FDA? 16 A. I'm going to give you two 17 answers, but they're not inconsistent. 18 MR. MYERS: When you say the 19 information attached, you mean what's attached to 20 this exhibit or what would have been attached to 21 the -- 22 Q. What would have been attached 23 to this facsimile that talks about Doctor Masica 24 and Doctor Leber had a phone call and newspaper Page 420 1 articles and things of that nature being 2 attached. 3 A. The two answers are yes and 4 yes. Yes for what would have been attached, and 5 yes for what is actually attached. 6 Q. Okay. In what situation would 7 you fax the information you talked about on the 8 first page of Exhibit 8 -- 9 A. Sure. 10 Q. -- to somebody like Mister 11 DeCicco? 12 A. Simply as an informational 13 item. It might help if I would explain who he 14 is, because he's a consumer safety officer for 15 that division. You may or may not know that, but 16 he's a consumer safety officer for that division, 17 he works directly with Doctor Leber. And, so, 18 this was an FYI, for your information, to Mister 19 DeCicco, but actually for Doctor Leber as it 20 turns out. 21 Q. Why did you feel it was 22 necessary to fax this information as opposed to 23 just transmitting it through the mail or 24 hand-delivering it? Page 421 1 A. Very simply because it looks -- 2 at least one of these, or maybe even more of 3 these instances, you're talking about four 4 different bullet points maybe, or four different 5 segments appear to be in the media, and no one 6 likes surprises, and we don't think the FDA likes 7 surprises either. So it was FYI'd on that basis, 8 please be advised this could be appearing in your 9 local newspaper, and here you have at least the 10 information that we have about it. 11 Q. So it was damage control, so 12 to speak. You wanted to get to the FDA before 13 they read the newspaper on this or got the 14 information from somebody else? 15 MR. MYERS: I object to the form of 16 the question, I think that's sort of an 17 argumentative characterization. 18 A. I wouldn't agree with damage 19 control. I think this is an FYI, that's the 20 characterization that I used earlier, and I think 21 that's it, for your information. 22 Q. Let's look at the second page 23 of the exhibit. 24 A. Sure. Page 422 1 Q. If you could look towards the 2 middle of the page where the first indentation 3 is. 4 A. Where it's indented, right, 5 there's a paragraph there. 6 Q. It says we have undertaken a 7 comprehensive analysis using a cluster of defined 8 event terms, comma, quote, the aggression 9 cluster, unquote, paren, anti-social reaction, 10 comma, hostility, comma, personality disorder, 11 close paren. Do you see that? 12 A. Yes, ma'am, it's there. 13 Q. And you wrote this letter, 14 correct, the second or third page of Exhibit 8? 15 A. I submitted this letter, I 16 signed this letter, but there are probably 17 elements of it that I did not write. 18 Q. Do you know where you got this 19 information about the aggression cluster? 20 A. I would have gotten it from a 21 physician, I can tell you that, it would not have 22 come from regulatory affairs, per se. 23 Q. Do you know which physician in 24 this case? Page 423 1 A. No, ma'am, I wouldn't. 2 Q. To the best of your 3 recollection, are there any other events included 4 in the aggression cluster other than anti-social 5 reaction, hostility and personality disorder? 6 A. I previously testified that I 7 didn't know the term aggression cluster, and at 8 least it appeared in one of my letters, but other 9 than knowing now that it appeared in one of my 10 letters, and there are, what, three terms here -- 11 Q. Right. 12 A. -- associated with it, I don't 13 know any more than I did a few minutes ago. 14 Q. So there may have been more 15 terms associated with cluster -- 16 A. The answer to your question is 17 yes, there may have been other terms. 18 Q. Please let me finish my 19 questions so she can get an accurate record. 20 A. I'm sorry. 21 Q. That's okay. But your 22 testimony is this information came from one of 23 the physicians at Lilly, this is not something 24 that you wrote from your understanding? Page 424 1 A. That's correct. 2 Q. Do you recall seeing this 3 letter in the boxes of documents that you 4 reviewed prior to today and yesterday? 5 A. No, this doesn't -- neither 6 this letter or the attachment to it, neither one 7 of them rings a bell. It's not to say that I 8 didn't even touch them or it's not to say that I 9 didn't see them, but I don't recall. 10 Q. Do you recall reviewing 11 reports related to violent/aggressive behavior 12 and the use of Prozac with Fluoxetine in general 13 from the documents that you reviewed from the 14 boxes? 15 A. No, ma'am. 16 Q. Would it also be true of the 17 next paragraph of indented -- the next indented 18 paragraph, starting on page one of the letter and 19 moving to page two, that information came from a 20 physician at Lilly? 21 A. Give me a second, Ms. Zettler, 22 and I will be sure. Yes, ma'am, I think that 23 would be the same as my response to the preceding 24 paragraph. Page 425 1 Q. Do you know for a fact that -- 2 going back to the first paragraph of the letter, 3 that all Fluoxetine clinical trials were analyzed 4 as it states there? 5 MR. MYERS: Where are you reading 6 from? 7 MS. ZETTLER: Second indented 8 paragraph. 9 A. Second, I'm sorry. I did not 10 conduct the analysis myself, if that's what you 11 mean by knowing for a fact. 12 Q. Do you have any reason to 13 believe that all Fluoxetine clinical trials were 14 not analyzed? 15 A. Absolutely no reason to 16 believe that, that they weren't. Maybe -- let me 17 rephrase because that's confusing. I have no 18 reason to disbelieve what is stated in this 19 second paragraph. 20 Q. How about with suicidality, do 21 you know what clinical trials were reviewed in 22 the reanalysis of data in preparation for the 23 1991 drug advisory committee meeting? 24 A. Is that associated with this -- Page 426 1 oh, okay -- 2 Q. No. 3 A. Would you mind repeating the 4 question? 5 MS. ZETTLER: Could you read it back? 6 (THE COURT REPORTER READ BACK THE 7 REQUESTED TESTIMONY.) 8 A. No, ma'am, I don't. 9 Q. Do you know if it was all 10 clinical trials? 11 A. I don't remember, ma'am, I'm 12 not sure that I ever knew. 13 Q. Have you ever heard the term 14 hits, H-I-T-S, used in conjunction with Lilly? 15 A. I was going to say -- no. I 16 can infer what it would mean, it might mean that 17 you pick up something. 18 Q. Pick up something, what do you 19 mean? 20 A. If you're doing an analysis, I 21 remember from the laboratory, that's my 22 recollection of it, and you would run some tissue 23 match samples, for example, and you would be 24 comparing an experimental tissue versus some Page 427 1 known standards, and then you would be 2 characterizing that experimental tissue by the 3 number of known standards that it hit, and those 4 were then hits. That's all I know. I've never 5 used it since I left the laboratory, I'm sure. 6 Q. Are you aware that a group of 7 Lilly employees from Indianapolis went to various 8 affiliates in Europe and outside the United 9 States to review clinical report forms from 10 double-blind controlled studies to not only 11 gather data but to see whether or not there were 12 suicidal ideation related adverse events that 13 occurred during those trials? 14 A. You have more details than I 15 have. I knew that there were a group of Lilly 16 employees that went to the affiliates, and then 17 what happened after that, I don't know. 18 Q. So you haven't heard the term 19 hits related to that project, have you? 20 A. Not that I can recall. The 21 only hits, as we referred to them in scientific 22 or medical sense, relates back to my laboratory 23 days, and I described that to you. 24 Q. Other Lilly employees have Page 428 1 testified that as a result of that project of 2 going over to the other affiliates, the outside 3 U.S. affiliates, and collecting data, that a 4 number of suicidal ideation related adverse 5 events or reports of suicidal ideation adverse 6 events occurring during clinical trials reviewed 7 were transmitted back to Eli Lilly in 8 Indianapolis and then reviewed by clinical 9 research physicians here in Indianapolis. Were 10 you aware of that? 11 A. That specifically doesn't come 12 to mind, no. I have no reason not to believe 13 that. 14 Q. Were you aware that those 15 physicians who reviewed those instances or 16 reports of instances of suicidality adverse 17 events made an independent judgment or made their 18 own judgment as to whether or not those events 19 were in fact related to suicide or suicidal 20 ideation? 21 A. I didn't know that -- or I 22 don't know that would be the better response. 23 Q. What types of doctors were 24 retained by Lilly to conduct clinical trials on Page 429 1 Fluoxetine, like what kind of specialties did 2 that practice, to your knowledge? 3 A. Well, again, as we discussed 4 not only the last couple of days but when we've 5 been together before, I do not have very much, if 6 any, connection at all with the administration of 7 clinical trials. I do know there were some 8 psychiatrists, and that's the best that I can do 9 for you. 10 Q. Would you agree that the 11 majority of clinical investigators that conducted 12 human trials on Fluoxetine for depression were 13 psychiatrists? 14 A. I wouldn't even go that far. 15 I don't know, they may have been, they may not 16 have been. I knew there were psychiatrists that 17 conducted the Prozac trials, if we go any farther 18 than that, we're outside of my realm of 19 knowledge. 20 Q. Do you consider the quality of 21 the clinical investigators retained by Lilly to 22 perform clinical trials on Fluoxetine as being 23 high, like high quality individuals? 24 A. That really calls for me, A, Page 430 1 to know who was retained, and again, as I 2 indicated, I don't know the individuals, and B, 3 for me, I think, to render some sort of clinical 4 judgment about their quality. If they were 5 regulatory people, I would be glad to answer your 6 question, but they're physicians, and I probably 7 better not answer that. 8 Q. Would you expect Lilly to hire 9 schlock doctors to run their clinical trials? 10 A. I happen to understand a 11 little Yiddish, and in this case, no, I don't 12 want to be involved with anything that schlock. 13 Q. Do you have any reason to 14 believe that research physicians at Lilly would 15 have any question -- any reason to question a 16 clinical investigator's reporting of an adverse 17 event as suicidal ideation related to Fluoxetine? 18 MR. MYERS: Let me object to the form 19 of that question in that it calls for an awful 20 lot of speculation with no definition of the 21 clinical investigator or the physician or the 22 circumstances under which you described them and 23 under which they occurred or didn't occur. If 24 you know or if you're able to answer, Doctor Page 431 1 Talbott, answer. 2 A. Well, my discomfort really in 3 trying to answer comes again from, at least as I 4 interpret that question, is asking me to have 5 some clinical judgment and to say well, how do 6 physicians operate with each other, can one 7 physician have a different view of an issue than 8 another, and that -- I'm really not that familiar 9 with medicine, I'm not a clinician, and I would 10 feel really uncomfortable because I'm a lay 11 person in regards to clinical decisions. So 12 again, if it were regulatory people, I would be 13 glad to give you not only an opinion, but an 14 educated opinion. But in this case, I really 15 would feel uncomfortable to answer, I'm sorry. 16 Q. Do the regulations with regard 17 to reporting of adverse events dictate as to what 18 degree of follow-up with regards to each adverse 19 event is necessary on the part of the 20 manufacturer? 21 A. I think they do to the extent 22 that as we have follow-up information, not 23 surprisingly, we're obligated to report that. So 24 yes, there are. And don't ask me which Page 432 1 subsection. I believe it is under that 314.80 2 that we've been talking about before. It's in 3 the general NDA requirement, but I don't know 4 which section. But there is a section in there 5 that says follow-up information must be reported, 6 and which of course we comply with. 7 Q. Is there anything in the 8 regulations that compels Lilly to follow up on 9 adverse events reported to it? 10 A. Again, remember our assumption 11 is until you tell me otherwise, we're talking 12 about spontaneous events, and I don't believe 13 there is, Ms. Zettler. 14 Q. How about events reported 15 within clinical trials? 16 MR. MYERS: Which of your question? 17 You asked a couple of questions, so which of your 18 questions? 19 Q. Is there anything in the 20 regulation that compels Lilly to follow up on 21 reports of adverse events occurring during 22 clinical trials? 23 A. I believe that we have -- I'm 24 not sure that you could say in black and white, Page 433 1 but I think that we have taken the position that 2 follow-up on clinical trial adverse events is a 3 general policy for us to take, and that very 4 candidly, I mean just looking at it from my point 5 of view, and this is not as a clinician, but just 6 as a regulatory person, we spend the time 7 accumulating the data on these patients, and we 8 will really perhaps shortchange ourselves if we 9 didn't do the follow-up. 10 Q. Is -- 11 A. And then -- I'm sorry to 12 interrupt you, but then report that information 13 as the regulation mandated. 14 Q. Have you ever heard the phrase 15 "lost to follow up" used in relationship to the 16 clinical trials? 17 A. To clinical trials, yes, 18 ma'am, I have. 19 Q. And at what point does one 20 become lost to follow up if you're a patient on a 21 clinical trial? 22 A. I really don't know. I think 23 that's one that would probably be better directed 24 at the physicians or the people that administer Page 434 1 the clinical trials. Again, remember a few 2 moments ago we were talking about it, I do not 3 get involved with the administration of clinical 4 trials at all, so other than being familiar with 5 the term and knowing what it means, I can't give 6 you a definition. In other words, if somebody is 7 lost to follow up, if you've not heard from them 8 in a day or lost to follow up in six months or 9 six years, I don't know, I can't help you. 10 Q. Do you know what the policy is 11 at Lilly as to how much of an attempt to contact 12 the patient must be made by the clinical 13 investigator or somebody on his staff before 14 somebody becomes lost to follow-up? 15 A. I'm not aware of any policy. 16 There may very well be, but I'm not aware of any. 17 Q. Where would such a policy be 18 listed if there is one? 19 A. Probably be in some of the 20 procedures for the clinical trial administration 21 area, I would imagine. Again, that's just a 22 guess, but that would seem logical. I know -- I 23 can testify that there is not such a policy in 24 the regulatory procedures that we have for the Page 435 1 regulatory area. 2 MS. ZETTLER: Let's take a break here 3 for lunch and come back at 1:00. 4 MR. MYERS: That's fine. 5 (A SHORT LUNCH RECESS WAS TAKEN.) 6 Q. (BY MS. ZETTLER) Doctor, with 7 regards to adverse events that occurred during 8 the clinical trials, are all of those reported 9 through a form 1639 regardless of whether or not 10 they're serious or alert? 11 A. That would be clinical trial 12 events? 13 Q. Right. 14 A. No. 15 Q. Are any of the clinical trial 16 adverse events reported through 1639s? 17 A. Yes, some are. 18 Q. Which ones? 19 A. The ones that are serious and 20 unexpected, and to use the FDA's term, and I put 21 this in quotes, reasonably, possibly, causally 22 related, close quotes. 23 Q. Reasonably, possibly, causally 24 related? Page 436 1 A. Causally related. 2 Q. Causally related. Regardless 3 of whether or not they occurred in clinical 4 trials here or outside the United States? 5 A. If they're conducted under the 6 IND, that's immaterial. 7 Q. How about if they're conducted 8 under the NDA? 9 A. By definition then, and I 10 think this is correct, although I don't exactly 11 remember what the regulations say, there's really 12 only one type of study, and they don't even call 13 it a trial, that could conceivably be done under 14 the NDA, and that's a post-marketing surveillance 15 study. So with that definition in mind, any 16 other study or trial would be under the IND, at 17 least to my way of thinking. 18 Q. What is a post-marketing 19 surveillance study? 20 A. Again, I'm not an 21 epidemiologist, but my understanding of that from 22 the regulations is that this is a study that's 23 conducted on a product after that product's 24 approval. Page 437 1 Q. For any particular purpose or 2 can it be, like, for example, an efficacy study? 3 A. No, I believe it's primarily -- 4 by the use of the term surveillance, it's 5 primarily directed at safety data. 6 Q. What is a Phase 4 study? 7 A. To me, it could be a couple of 8 things really. I sometimes use, and I might be 9 incorrect, but I sometimes use Phase 4 and 10 post-marketing surveillance interchangeably. And 11 then I've also heard people, although I don't do 12 this much, or any, for that matter, but I've also 13 heard people calling studies for new indications 14 or just additional experience on an already 15 approved drug as a Phase 4. I don't know that 16 there is in the regulations, and I'm trying to 17 recall, but I don't think there is a specific 18 definition of Phase 4. I could be corrected on 19 that, though, if shown the documents. 20 Q. If you conduct a study, the 21 second category that you were talking about -- 22 A. Right. 23 Q. -- on other indications or 24 additional experience on an approved indication, Page 438 1 would those be filed under the IND or NDA? 2 A. Normally if they were a new 3 indication, I would advise filing it under the 4 IND. 5 Q. How about if it's additional 6 experience on approved indication? 7 A. We got into this a little bit 8 yesterday, so I'll try to recap what I had said 9 there. My understanding of the regulations is 10 that if the use in that study is consistent with 11 what the approved indications and usage, et 12 cetera, in other words consistent with the 13 package insert and product label, then that 14 probably does not require any investigational 15 application with the agency. However, if there's 16 any deviation from the conditions approved by the 17 agency, then I would advise it would probably be 18 under the IND, submitted to the IND. 19 Q. So for example with regards to 20 post-marketing studies on Fluoxetine, studies, 21 for example, looking at the efficacy of Prozac on 22 people who were suffering from depression, say an 23 agitated type or something, would fall under the 24 NDA, where somebody -- a study looking at Page 439 1 treating OCD with Fluoxetine would fall under an 2 IND? 3 A. I'll answer the last half. I 4 would say that OCD -- in fact, I know this to be 5 the case, our OCDs were done under the IND. 6 Depression -- and you may, in fact, I'm sure you 7 do know the distinction better than I, depression 8 is depression to me. So I don't know about 9 agitated depression, I don't even know what that 10 is. I know it's some form of depression on the 11 basis of the term, so I can't give you a specific 12 where that would go. I would say in the case of 13 OCD I can give you another example. Bulimia, for 14 example, studies on that would be done under the 15 IND, et cetera. 16 Q. But you don't know if, say, an 17 additional efficacy study was done using 18 Fluoxetine to treat depression after 19 post-marketing, if that would be an IND or NDA? 20 A. I would just have to look at 21 the circumstance. I would be willing to give you 22 a judgment if we had some circumstances and I had 23 a chance to look at the regs, maybe, and research 24 it. Page 440 1 Q. Okay. Just so I understand 2 your testimony, it was Lilly's policy, and still 3 is Lilly's policy, to file a 1639 related to any 4 spontaneous adverse event they become aware of 5 other than what we talked about this morning 6 regarding the outside the United States adverse 7 events? 8 A. That's correct. And just to 9 clarify for the record, then, I believe my 10 testimony was any outside the U.S. non-alerts. 11 Q. Okay. 12 A. Outside the U.S. alerts are 13 treated exactly the same way as domestic alerts. 14 Q. Do you know of any situation 15 with regards to Fluoxetine where United States 16 spontaneous adverse events that Lilly became 17 aware of, either by happenstance or through 18 direct reporting to Lilly, where they did not 19 file a 1639 related to those adverse events? 20 A. Spontaneous -- 21 Q. Right. 22 A. -- U.S. did not file a 1639, 23 no, ma'am, I do not know of any instance. 24 (PLAINTIFFS' EXHIBIT NO. 9 WAS Page 441 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 Q. Have you had a chance to read 4 Exhibit 9? 5 A. Yes, ma'am. 6 Q. Do you recall this exhibit or 7 recognize this exhibit? 8 A. No, I don't. And I think 9 yesterday we identified Mister Barash. I think I 10 called him incorrectly yesterday, Doctor Barash, 11 and as it turned out it appears he's a pharmacist 12 here. But he's in the statistics branch, as I 13 indicated, at the FDA. 14 Q. What is the Rocky Mountain 15 Poison Control Center, if you know? 16 A. Other than what the title 17 implies, that's as much as I know about them. 18 Q. The exhibit is a letter from 19 Mister Barash to you, correct? 20 A. Yes, it is, dated, just for 21 the record, I don't know if we mentioned or not, 22 but April 22, 1991. 23 Q. Okay. And in his letter to 24 you, Mister Barash is discussing Lilly's proposal Page 442 1 to submit highlighted summaries of study 2 tabulation data and PAER reports rather than 3 filing 1639 reports for non-fifteen-day reports 4 of adverse events, correct? 5 A. Yes, that's the first sentence 6 in the second paragraph. 7 Q. Do you know what adverse 8 events he's referring to? 9 A. Well, just -- again, I can't 10 specifically -- I don't specifically recall the 11 letter, and therefore I couldn't tell you which 12 particular cases, but the inference I draw here 13 is it would be study reports of overdose cases 14 from this center that we were talking about. 15 Q. Is it your impression that 16 overdoses are the adverse events that are 17 occurring in this circumstance? 18 MR. MYERS: Excuse me, are occurring? 19 MS. ZETTLER: Right. 20 A. Well, study reports of 21 overdose cases. I just play that back. I think 22 that's what he's referred to here and that's what 23 I feel comfortable with saying. 24 Q. Are you aware of a Page 443 1 post-marketing surveillance study which Lilly 2 participated with the Rocky Mounty Poison Control 3 Center to study incidence of overdoses with 4 antidepressant drugs? 5 A. Recall none, but again, the 6 inference I can draw from the documents you've 7 just given me, it looks like there was a 8 post-marketing surveillance study with Rocky 9 Mountain Poison Control Center, and it talks 10 about our involvement with that. So the 11 inference would be it appears to be something 12 like that, yes. 13 Q. Do you know how many adverse 14 events of overdose were reported to Lilly by the 15 Rocky Mountain Poison Control Center related to 16 Fluoxetine during this study? 17 A. No, ma'am, I don't. 18 Q. Do you have an opinion as to 19 whether or not, in this circumstance, overdoses 20 would be considered fifteen-day alert report 21 adverse events? 22 MR. MYERS: Before he answers, let me 23 object to the form "in this circumstance." I'm 24 not sure what the circumstance is. Page 444 1 MS. ZETTLER: Overdoses of Fluoxetine 2 or overdoses experienced by people on Fluoxetine. 3 MR. MYERS: If you understand the 4 question. 5 A. I think I do. Well, again, 6 we've talked earlier, I didn't know about this 7 study or a study, per se, but I can infer from 8 this he's talking about what the FDA designates 9 as non-alert experience reports. So I think 10 that's a response then to your question, at least 11 as I understood the question. We're talking 12 about non-alert drug experience reports here. 13 Q. Right. But I mean do you know 14 how many of the reports that were submitted to 15 Lilly by the Rocky Mountain Poison Control Center 16 would have been considered alert as opposed to 17 non-alert? 18 A. No, ma'am, I don't. 19 Q. Okay. And from this exhibit 20 is it your understanding that the FDA agreed to 21 allow Lilly to report non-alert adverse events 22 that were uncovered because of this study in 23 highlighted tabulations as opposed to through 24 1639s? Page 445 1 MR. MYERS: I object to the form only 2 to the extent you use the term uncovered, and 3 that's awfully vague and undefined. If you 4 understand it, go ahead, Doctor. 5 A. I quibble with that same word, 6 but let me see if I can -- 7 Q. Let me switch it to reported. 8 A. Okay, that's fine, I 9 appreciate that. Actually as I read this here, 10 it would suggest that we were proposing 11 submitting reports of some form or another, I 12 think there was a tabulation mentioned, there 13 were 1639s mentioned. But Mister Barash is 14 drawing our attention to the fact in the second 15 sentence of the second paragraph, as you know, 16 the non-alert drug experience reports that we're 17 talking about here from post-marketing 18 surveillance studies are not required to be 19 submitted. I guess what we were working here was 20 we felt like these data should be submitted, we 21 asked FDA that even though they don't have a 22 requirement to submit, would there be any 23 prohibition against us making submissions by 24 virtue of a tabulation. And I think that's what Page 446 1 he's okaying here. Again, I'm inferring this 2 from what's in front of me. 3 Q. Would reports of adverse 4 events coming to Lilly as a result of this study 5 be considered spontaneous adverse event reports 6 or would they be considered clinical trial 7 adverse event reports? 8 A. I see the term post-marketing 9 surveillance studies here, and that's a term, as 10 we talked a little bit earlier today, that shows 11 up in the NDA portion of the regulations. So I 12 would say this would probably be the NDA side. 13 Q. Which would mean it would be 14 spontaneous or clinical? 15 A. I'm sorry, spontaneous. 16 Q. And earlier you testified that 17 it was your understanding that it was and is 18 Lilly's policy to report all spontaneous adverse 19 events via 1639s, regardless of whether or not 20 they were serious and unexpected, correct? 21 A. I think at that time we were 22 discussing about nonpost-marketing surveillance 23 studies, we were talking about just the general, 24 and I think yesterday we used the term garden Page 447 1 variety in one of our discussions, and I'll use 2 that today, general garden variety types of 3 adverse event reports. Post-marketing 4 surveillance studies are actually, and if you 5 look at regulations, they're covered in a 6 different section under 314.80, and they're 7 treated differently than normal spontaneous 8 studies. For example -- yes, for example, he 9 notes here, the combination of the two terms, 10 fifteen-day study reports, and having undergone a 11 causality screening, that's a referral to the 12 portion of regulation that talks about the 13 post-marketing surveillance studies. Even though 14 it's under the spontaneous portion of the adverse 15 event reporting for NDA, they undergo a causality 16 check in addition to seriousness and unexpected. 17 So to be an alert report from a post-marketing 18 surveillance study conducted on an NDA drug, they 19 have to be serious, and we talked about serious 20 before. They have to be unexpected, and we 21 talked about that before. And they then have 22 that additional requirement of reasonable, 23 possible, causal relationship that we talked 24 about a little bit earlier on the clinical Page 448 1 trials. So there are actually three criteria 2 that are used to check these. So what I'm 3 thinking about here is that even though they're 4 under the NDA, even though we're talking about 5 spontaneous events, I would put post-marketing 6 surveillance studies in a little bit different 7 category than the common garden variety 8 spontaneous events we talked about. So I make a 9 distinction, then, about 1639s for all Lilly 10 spontaneous events from usage, and 1639s on Lilly 11 events from post-marketing surveillance studies 12 that because of regulations we consider to be 13 spontaneous events. 14 Q. In this situation Lilly was 15 really monitoring information that was being 16 gathered by the Rocky Mountain Poison Control 17 Center as far as you know? 18 A. Monitoring is kind of a 19 specific term for me. Let's say I would respond 20 in the affirmative to say Lilly was staying in 21 touch with Rocky Mountain Poison Control Center, 22 because monitoring has almost a specificity to 23 it, in fact I think it's even defined under the 24 regs. Page 449 1 Q. But I guess the point I'm 2 trying to get at is this is not a study that was 3 specifically set up by Lilly where they asked 4 Rocky Mountain Poison Control Center to seek out 5 people who had overdose or things of that nature, 6 this is just a surveillance or evaluation or 7 gathering of data that was gathered by Lilly that 8 was gathered by the Rocky Mountain Poison Control 9 Center? 10 MR. MYERS: Before he answers, let me 11 object to the form only to the extent, Nancy, a 12 number of questions back he said he didn't really 13 know much about the study, and now you're trying 14 to characterize it and I don't know if he's able 15 to do that. 16 MS. ZETTLER: If he can't, he can tell 17 me. 18 A. I can give you a couple of 19 responses to that. I really don't recall the 20 circumstances of this, but clearly it appears 21 that, at least from this document here, that the 22 Rocky Mountain Poison Control Center really was 23 the initial collector of the information, and 24 then what our relationship with them, I can't Page 450 1 recall. I'm sure it would be available in some 2 documents back and forth between us and the 3 center or whatever, but other than that, I'm 4 afraid I can't help you too much. 5 Q. In normal circumstances where 6 you're not conducting a post-marketing 7 surveillance study, would an entity such as the 8 Rocky Mountain Poison Control Center communicate 9 adverse events that it has seen in people using 10 Fluoxetine to Lilly or other drug manufacturers 11 depending on the drug? 12 MR. MYERS: When you say normal 13 circumstances, you mean not a clinical trial? 14 MS. ZETTLER: I said normal 15 circumstances outside of the post-marketing 16 surveillance study type situation. 17 A. I don't know, I don't think I 18 can answer that, I really don't know what their 19 practice is. As you can tell, I don't have a 20 day-to-day familiarity with, what is it, the 21 Center, so I really don't know what their normal 22 practice would be. It looks here, though, just 23 inferring from this, that we had asked to get 24 tabulations or cases from them. So for this Page 451 1 specific instance, as represented by this 2 specific letter, it looked like we had a 3 communication or agreement or arrangement with 4 them, but I don't know what the normal process 5 would be for them. 6 Q. Besides the common garden 7 variety spontaneous reports and the category that 8 you delineated in which these reports made by the 9 Rocky Mountain Poison Control Center would fall 10 in the post-marketing surveillance study, are 11 there any other categories of spontaneous adverse 12 event reports in your mind? 13 A. Well, there are all sorts of 14 different ways of slicing each of those. And 15 let's rephrase common garden variety because 16 that's flippant, and I apologize for that. Let's 17 say standard types of spontaneous event reports 18 because there's really nothing common or garden 19 variety about adverse events. So I would think 20 with standards such as we talked about, and with 21 post-marketing surveillance, if I use the 22 regulations really kind of as the categorization, 23 at least under NDA those seem to be the two 24 biggest chunks. Now we might be able to slice Page 452 1 and dice that a bit on circumstance, but I think 2 those are the two biggest chunks. And by slice 3 and dice, I mean really kind of subdivide certain 4 kind of criteria under that. But those are the 5 two major subdivisions under NDA rules, and 6 because they're under NDA rules, then we kind of 7 put these both under the heading of spontaneous. 8 Q. Who makes the causality screen 9 that he talks about in the last full paragraph? 10 A. When I read that I was trying 11 to decide, because to me a screen means like on a 12 computer, and I wondered, because I don't enter 13 these adverse events myself, I thought at first 14 he meant well, the screen on the computer comes 15 up and it has causality questions, but I think 16 what he meant was a screen process. And under 17 that definition, then that's done by the 18 physicians at Lilly. 19 Q. So anytime a determination as 20 to whether or not an event is reasonably, 21 possibly, causally related to the use of, say, 22 Fluoxetine is made, that is done by the research 23 physicians, the physicians at Lilly? 24 A. The physicians at Lilly, yes, Page 453 1 ma'am. 2 Q. Does the FDA have input into 3 that? 4 A. After they've seen our 5 judgments, they can comment on them. 6 Q. Have you ever seen a case 7 where that's happened with regards to Fluoxetine? 8 A. I can't remember -- not with 9 Fluoxetine I can't recall any. 10 (PLAINTIFFS' EXHIBIT NO. 10 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Have you had a chance to 14 review Exhibit 10? 15 A. Yes, ma'am, an April 12, 1991 16 letter. I designated him Doctor Barash here, so 17 at least I had some precedent to my misstatement 18 from me, Doctor Barash being at FDA -- or Mister 19 Barash. 20 Q. You wrote this letter -- you 21 wrote to David Barash at the FDA? 22 A. It's a letter I sent. I'm not 23 sure if it was with you or Mister Smith, but we 24 generate so much correspondence, et cetera, that Page 454 1 today, under oath, speaking to you, I can't say 2 that I wrote this letter. I did obviously read 3 this letter and sign it and send it, so that I'm 4 sure of. 5 Q. Actually you didn't sign this, 6 did you, your signature isn't on here, is it? 7 A. There's not a signature on the 8 one I've got, that's right. 9 Q. So you're not sure whether or 10 not you actually wrote this letter, are you? 11 A. I can't testify today one way 12 or the other. 13 Q. Would the fact that you don't 14 have any recollection about this study indicate 15 to you one way or the other whether or not you 16 wrote this? 17 A. No, because I -- 18 conservatively I probably submitted thousands of 19 documents since that time. It's, what, almost 20 three years exactly. 21 Q. But this letter could also 22 have been written to the FDA by somebody else 23 over your signature line? 24 A. Yes. But our general process, Page 455 1 and I think we talked about that this morning, is 2 that I would be notified and apprised of the 3 letter. So I should have had some knowledge of 4 this letter if my signature block were used. 5 Q. Do you recall one occasion 6 with regards to Fluoxetine where you refused to 7 allow somebody to write a letter to the FDA over 8 your signature or your signature line? 9 A. I can't recall that. 10 Q. You don't recall one instance? 11 A. No. 12 Q. Do you recall an instance 13 where you've questioned somebody using your 14 signature line or your name on a letter that they 15 were sending to the FDA with regards to 16 Fluoxetine? 17 A. With regards to Fluoxetine, 18 no. 19 Q. Would you insist on reading 20 every letter before it went out over your 21 signature line? 22 A. At the very least, the cover 23 letter, and if we had attachments, on occasion I 24 would perhaps read all of them, on occasion would Page 456 1 review, at the very least, even any instance, as 2 for example, our most ponderous submissions, like 3 full NDAs, I will take time to actually go 4 through those NDAs, even though they may be three 5 or four hundred volumes, making sure of format, 6 consistency, about language, terminology, et 7 cetera. And I won't represent to you today that 8 I read every page or every word on every page of 9 a four or five hundred volume submission, but 10 generally would not submit anything unless I was 11 at least passingly familiar with the attachments 12 to it, and certainly very familiar and 13 comfortable with the actual cover letter or 14 transmittal letter. 15 Q. What about in a case such as 16 this where a letter is going to Mister Barash 17 proposing a change in the reporting process, 18 would you have insisted on reading a letter like 19 this if it went out over your signature? 20 A. My normal procedure would have 21 been, yes. 22 Q. Even if you were out of town? 23 A. Could have that read to me 24 over the phone or faxed. Page 457 1 Q. Do you recall doing that? 2 A. For this particular letter? 3 Q. For any letter. 4 A. Yes. 5 Q. How many occasions? 6 A. Probably a dozen, in fact I'm 7 expecting one right now. 8 Q. A dozen in the entire time 9 that you've worked on Fluoxetine? 10 A. Since I have been a regulatory 11 scientist, which would be the same, yes. 12 Although, you understand I'm not a regulatory 13 scientist anymore. That sounded like I was 14 continuing to be. 15 Q. Have you ever heard CIOMS 16 working group, C-I-O-M-S? 17 A. Sure. 18 Q. What is the CIOMS working 19 group? 20 A. Well, let me define CIOMS 21 first. That's the World Health Organization's 22 Counsel of International Organizations of Medical 23 Science. So it's kind of an organization of 24 organizations. And they have over the years had Page 458 1 various working groups on various aspects of 2 regulations in medicine. 3 Q. Were you a member of that 4 group? 5