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. DOROTHY DOBBS 11 DATE: JULY 11, 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. ) 22 COMES DR. DOROTHY DOBBS, CALLED BY THE 23 PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, WAS 24 DEPOSED AND TESTIFIED AS FOLLOWS: Page 2 1 * * * * * * * * * * Page 3 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 4 1 * * * * * * * * * * 2 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS 3 COUNTY DEPARTMENT - LAW DIVISION 4 RENATO DI SILVESTRO, Individually ) and as Special Administrator of ) 5 the Estate of JOHN DI SILVESTRO, ) Deceased, ) 6 ) Plaintiff, ) 7 ) v. ) No. 91 L 7881 8 ) ROBERT L. NELSON, et al., ) 9 ) Defendants, ) 10 ) GEORGE MELNICK, M.D. and PETER ) 11 FINK, M.D. ) ) 12 Respondents in Discovery.) 13 * * * * * * * * * * Page 5 1 IN THE CIRCUIT COURT OF THE SIXTH JUDICIAL CIRCUIT CHAMPAIGN COUNTY, ILLINOIS 2 LINDA GARDNER, Individually and ) 3 as Special Administrator of ) the Estate of SHANE GARDNER, ) 4 deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91 L 1066 ) 7 ELI LILLY AND COMPANY, a foreign ) corporation, ) 8 ) Defendant. ) 9 10 * * * * * * * * * * Page 6 1 SUPERIOR COURT OF THE STATE OF CALIFORNIA 2 FOR THE COUNTY OF LOS ANGELES 3 DR. MARIUS SAINES, etc., et al., ) Case No: 4 ) SC 008331 Plaintiffs, ) 5 ) vs. ) 6 ) ELI LILLY & COMPANY, a corporation; ) 7 DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1- ) 8 100, inclusive, ) ) 9 Defendants. ) ____________________________________) 10 11 * * * * * * * * * * 12 NO. 93-8792-D 13 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF 14 INDIVIDUALLY AND AS SURVIVORS ) AND STATUTORY BENEFICIARIES ) 15 OF MAY YUN KUNG, DECEASED ) ) 16 VS. ) DALLAS COUNTY ) T E X A S 17 ELI LILLY AND COMPANY, DISTA ) PRODUCTS COMPANY, AND MONIQUE ) 18 KUNKLE, PH.D. ) Page 7 1 * * * * * * * * * * 2 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS 3 CIVIL COURT DEPARTMENT 4 EUGENE HUSLIG, AS ADMINISTRATOR ) 5 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 6 HUSLIG, DESCEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 7 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 8 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 9 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 10 ) 94 C 192 PLAINTIFFS, ) 11 ) VS. ) 12 ) COURT NO. 7 MARY L. BILLINGSLEY, EXECUTOR OF ) CHAPTER 60 13 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 14 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 15 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 16 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 17 ) DEFENDANTS. ) Page 8 1 * * * * * * * * * * 2 3 CAUSE NO. 93-04911-A 4 LINDA JILL WELCH, CARLINDA 5 WELCH REX, CONNAN ROSS WELCH AND CHAD MICHAEL WELCH, 6 INDIVIDUALLY AND AS SURVIVORS AND STATUTORY BENEFICIARIES 7 OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 8 V. 9 ELI LILLY AND COMPANY, DISTA PRODUCTS COMPANY, NOE NEAVES, 10 M.D., AND MINITH-MEIER CLINIC, P.A. DEFENDANTS Page 9 1 THE DEPOSITION OF DR. DOROTHY DOBBS TAKEN 2 AT THE BEST WESTERN MOTEL, LEESBURG, VIRGINIA, ON 3 JULY 11, 1994; SAID DEPOSITION TAKEN PURSUANT TO 4 NOTICE IN ACCORDANCE WITH THE RULES OF CIVIL 5 PROCEDURE. 6 * * * * * * * * * * 7 A P P E A R A N C E S 8 9 PAUL SMITH COUNSEL FOR PLAINTIFFS 10 745 CAMPBELL CENTER 2 8115 NORTH CENTRAL EXPRESSWAY 11 DALLAS, TEXAS 75206 12 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 13 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 14 JOE FREEMAN 15 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 16 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 17 ATLANTA, GEORGIA 30308-3243 Page 10 1 I N D E X 2 3 DEPOSITION OF DR. DOROTHY DOBBS 4 5 6 DIRECT EXAMINATION BY MS. ZETTLER 12 7 EXAMINATION BY MR. SMITH 113 8 CERTIFICATE OF SERVICE 219 9 10 ERRATA 220 11 12 EXHIBITS 13 PLAINTIFFS' EXHIBIT NO. 1 67 14 PLAINTIFFS' EXHIBIT NO. 2 75 PLAINTIFFS' EXHIBIT NO. 3 80 15 PLAINTIFFS' EXHIBIT NO. 4 86 PLAINTIFFS' EXHIBIT NO. 5 96 16 PLAINTIFFS' EXHIBIT NO. 6 118 PLAINTIFFS' EXHIBIT NO. 7 125 17 PLAINTIFFS' EXHIBIT NO. 8 129 PLAINTIFFS' EXHIBIT NO. 9 183 18 PLAINTIFFS' EXHIBIT NO. 10 201 Page 11 1 2 MR. FREEMAN: Let me just state at 3 this time a little brief stipulation. This is 4 the deposition of Doctor Dorothy Dobbs, taken on 5 behalf of the plaintiffs for purposes of 6 discovery and use at the trial on any of the 7 cases heretofore recited. The deposition of 8 Doctor Dobbs is taken by agreement of counsel and 9 by notice in the offices of Baker and Daniel in 10 Indianapolis. 11 Objection will be made at this time as 12 to any leading questions that Doctor Dobbs' own 13 counsel may put to her or any objection that any 14 lawyer may have to the witness' response to the 15 questions propounded. All other objections will 16 be reserved until the time of court hearing. 17 * * * * * * * * * * 18 19 DIRECT EXAMINATION 20 BY MS. ZETTLER: 21 Q. Doctor Dobbs, have you given a 22 deposition before? 23 A. Yes. 24 Q. On how many occasions have you Page 12 1 given a deposition? 2 A. Three or four. 3 Q. So you're familiar with the 4 ground rules about audible answers and taking 5 breaks when you want to, and if my question 6 doesn't make sense or if you don't understand it 7 for some reason, asking me to repeat it? 8 A. Yes. 9 Q. On these three or four 10 occasions that you've given depositions in the 11 past, did those occasions have anything to do 12 with your employment at any given time or were 13 they personal matters? 14 A. The first one -- I'm trying to 15 remember. The first one was related to 16 employment. There was another one, much more 17 recently, when -- it was associated with some 18 consulting work that I was doing. And I said 19 three or four, I really don't remember the 20 specific occasions very much. 21 Q. Have you given a deposition in 22 any other Prozac case -- 23 A. No. 24 Q. -- to date? When you say the Page 13 1 first deposition was with regard to employment, 2 where were you employed at the time you gave that 3 deposition? 4 A. St. Elizabeth's Hospital. 5 Q. Other than for personal 6 reasons, have you testified in court before a 7 jury or a judge? 8 A. Yes. 9 Q. In what cases or instance did 10 you testify in court? 11 A. I testified probably several 12 hundred times. 13 Q. Do you act as an expert 14 witness? 15 A. Yes. 16 Q. How long have you been an 17 expert witness? Not in any given case, but how 18 long have you acted as an expert? 19 A. The first time was in the 20 '60s. I would have to spend a moment trying to 21 figure out what year, but -- 22 Q. Have you testified as an 23 expert as to FDA regulatory issues? 24 A. Yes. Page 14 1 Q. When was the last time you 2 testified as such an expert? 3 A. In the late '60s. 4 Q. Is that when you were working 5 for the FDA? 6 A. Yes. 7 Q. Were you testifying on behalf 8 of the FDA? 9 A. Yes. 10 Q. When you were working with the 11 FDA, did you ever testify on behalf of a drug 12 manufacturer? 13 A. No. 14 Q. When you say testified, did 15 you testify at a trial or did you testify, like, 16 for Congress or congressional subcommittees or 17 something of that nature? 18 A. I wasn't including the two or 19 three times that I testified before congressional 20 committees. The two that I had in mind were 21 hearings. 22 Q. When you testified before 23 congressional committees, were you an employee of 24 the FDA? Page 15 1 A. Yes. 2 Q. Can you tell me briefly about 3 each of those times that you testified before 4 congressional committees as an employee of the 5 FDA, generally what the subject matter of the 6 committee was? 7 A. This was related to the drug 8 control legislation that was enacted in, I think, 9 1970. I remember testifying on one occasion 10 concerning amphetamines and related compounds. 11 On another occasion, I testified on -- I believe 12 I did, I had anticipated it, whether this 13 actually occurred is not clear in my mind -- on 14 two drugs that were subject to abuse. 15 Q. Which drugs? 16 A. Talwin and Darvon. 17 Q. Who manufacturers Talwin or 18 who manufactured Talwin? 19 A. Sterling Winthrop. 20 Q. How about Darvon? 21 A. Eli Lilly and Company. 22 Q. When you say you testified 23 concerning amphetamines and related compounds, 24 what was the purpose of your testimony? Page 16 1 A. This is a long time ago and is 2 not entirely clear in my memory, but it was in 3 some way related to abuse potential. 4 Q. Did you have a particular 5 expertise in amphetamines and related compounds 6 that you were imparting to the committee? 7 A. I don't know about a 8 particular expertise, I had some knowledge and 9 they were within my area at FDA. 10 Q. How long were you at the FDA? 11 A. Approximately five years, 12 although in the interest of total accuracy, there 13 was one period of about a year when I was working 14 part-time at St. Elizabeth's and part-time at 15 FDA, and then I returned to FDA full time. 16 Q. When did you first start 17 working at the FDA? 18 A. I believe it was January, 19 1965. 20 Q. Until about 1970? 21 A. Until the end of 1970. 22 Q. What did you do at the FDA? 23 A. Initially I was a medical 24 officer, reviewing new drug applications. I Page 17 1 later transferred to the marketed drug -- or 2 actually it was called division of drug 3 surveillance. And still later, with a 4 reorganization, I was -- no, prior to the 5 reorganization I was director of the division of 6 neuropharmacology for drug surveillance, that is 7 marketed drugs. And then following a 8 reorganization, was director of the division of 9 neuropharmacologic drug products. 10 Q. Do you do any regulatory work 11 now? 12 A. No. 13 Q. Either for a drug company or 14 for a governmental agency? 15 A. No. 16 Q. When was the last time you did 17 regulatory work? 18 A. When I was at Lilly. 19 Q. When did you leave Lilly? 20 A. June, 1985. 21 Q. Have you kept up with any of 22 the changes in the regulations or anything of 23 that nature at the FDA? 24 A. No. Page 18 1 Q. Do you consider yourself at 2 the present an expert on regulatory compliance, 3 FDA regulatory compliance? 4 A. Not now, no. 5 Q. When you say that your last 6 position at the FDA was as director of the 7 division of neuropharmacological drug products, 8 would that be the same position that Paul Leber 9 is in now? 10 A. Yes. 11 Q. How long were you director of 12 that division? 13 A. About six months. 14 Q. So from about the middle of 15 1970 to the end of 1970? 16 A. Approximately, uh-huh. 17 Q. Where did you go after leaving 18 the FDA? 19 A. Abbott Laboratories, north 20 Chicago, Illinois. 21 Q. Know it well. 22 A. Currently Abbott Park, 23 Illinois. 24 Q. How long were you with Abbott? Page 19 1 A. Close to eleven years. 2 Q. Why did you leave the FDA? 3 A. The director of the Bureau of 4 Medicine or Bureau of Drugs, I can't remember 5 which it was called at that time, apparently felt 6 that I was not a good manager and asked me to 7 take another position. 8 Q. Another position within the 9 FDA? 10 A. Yes. 11 Q. Who was the director of Bureau 12 of Drugs at that time when you left? 13 A. Director Henry Simmons. 14 Q. Did he say in what way he felt 15 you were not a good manager? 16 A. I don't recall his exact 17 comments. 18 Q. Did he ask you to take a 19 particular other position at the FDA? 20 A. He suggested that I head up 21 FDA activities on drug abuse. 22 Q. You didn't want to do that? 23 A. No. 24 Q. Why not? Page 20 1 A. I wasn't interested. 2 Q. Did he give you any other 3 options within the FDA besides that position? 4 A. No. 5 Q. What did you do when you were 6 at Abbott? Just generally, I don't want to know 7 any compound or anything like that. 8 A. I was medical director for 9 corporate regulatory affairs. 10 Q. Did you have any particular 11 type of drug that you worked on, like psychiatric 12 drugs or things of that nature? 13 A. No, I was involved with 14 essentially a cross section of Abbott 15 Laboratories' products. 16 Q. When did you leave Abbott? 17 A. '82 -- '81. 18 Q. Why did you leave Abbott? 19 A. The then Chairman of the Board 20 favored a more autonomous divisional structure, 21 and essentially my job was to be abolished. 22 Q. And then when you left Abbott, 23 you went to Lilly? 24 A. Yes. Page 21 1 Q. And you were with Lilly until 2 June of '85, I believe you said? 3 A. Yes. 4 Q. We'll get into what you did at 5 Lilly in more detail a little bit later, but why 6 did you leave Lilly in June of '85? 7 A. In general, I wasn't finding 8 my role at Lilly very satisfying. 9 Q. Can you expand on that a 10 little bit, what was it about your role at Lilly 11 that wasn't satisfying? 12 A. The status of my position was 13 not really as high as had been the case at 14 Abbott. There were also some personal reasons, 15 having to do with family and so forth. 16 Q. What personal reasons? I 17 don't mean to get super personal, Doctor, it's 18 just that I need to get an accurate reading of 19 what happened. 20 A. Atlanta was my original home 21 town. At that time my parents were still living, 22 both in nursing homes. I was an only child, and 23 felt that I really wasn't living up to my 24 responsibilities. And I had a number of other Page 22 1 relatives scattered around the state. 2 Q. In Georgia? 3 A. In Georgia. 4 MR. SMITH: Can I hand you some 5 documents, Nancy? 6 MS. ZETTLER: No, I've got it under 7 control, Paul, thanks. 8 (DISCUSSION OFF THE RECORD.) 9 Q. What position were you hired 10 in at at Lilly? 11 A. Medical advisor, clinical 12 research and regulatory affairs. 13 Q. Did that position change, I 14 mean did you get another position or other 15 responsibilities while you were at Lilly or did 16 that pretty much stay the same? 17 A. It pretty much stayed the 18 same. 19 Q. Were you expecting to move up 20 to a higher position while you were at Lilly? 21 A. I had anticipated that, yes. 22 Q. What was it that made you 23 anticipate that? 24 A. Conversations prior to my Page 23 1 going to Lilly. 2 Q. Conversations with who? 3 A. Primarily Doctor Charles 4 Christensen. 5 Q. Was this when you were 6 interviewing for the job? 7 A. Yes. 8 Q. What did Doctor Christensen 9 say about your advancement with the company? 10 A. I certainly can't quote him at 11 this -- after this length of time. I certainly 12 had the impression that it was highly likely that 13 I would be promoted to a director position. 14 Q. Did he give you a time period 15 in which you might be promoted? 16 A. No. 17 Q. Were you promised a promotion? 18 A. No. 19 Q. Were you fairly confident that 20 you would be promoted? 21 A. Yes. 22 Q. Did there come a time then 23 that you realized you were not going to be 24 promoted? Page 24 1 A. Yes. 2 Q. When was that? 3 A. I don't remember exactly, 4 perhaps five or six months after I had been 5 there. 6 Q. So I understand this, you 7 accepted the job with the understanding, at least 8 in your mind, that you would eventually be 9 promoted to a director position, correct? 10 A. Yes. 11 Q. And then about six months 12 after you started your employment with Lilly, you 13 came to the realization that you would not be 14 promoted, right? 15 A. Yes. 16 Q. What happened that made you 17 believe that you would not be promoted? 18 A. I don't remember in every 19 detail, but there was one conversation with 20 Doctor Christensen. 21 Q. Did he tell you that you were 22 not going to be promoted? 23 A. Yes. 24 Q. Did he tell you why you were Page 25 1 not going to be promoted? 2 A. The only specific comment that 3 I can recall was that I called attention to 4 problems without offering solutions. 5 Q. What type of problems? 6 A. Two areas occur to me. One 7 had to do with record keeping on disposition of 8 investigational drug supplies. 9 Q. Anything else? 10 A. The other was the facility 11 that Lilly used for Phase 1 studies at the local 12 county hospital, the name of which escapes me. 13 Q. Wishard? 14 A. Yes. 15 Q. And what about them? 16 A. At Christensen's request, I 17 performed an audit of certain of those records. 18 If I recall, the audit was focused on one or two 19 drugs. 20 Q. What drugs? 21 A. One was Nabilone. I'm not 22 sure whether there was a second, and if so, I 23 don't remember what it was. 24 Q. Did you audit Wishard records Page 26 1 on fluoxetine trials? 2 A. I may have, I'm not sure. 3 Q. When you began at Lilly, was 4 Oroflex marketed? 5 A. No. 6 Q. Was it still in the 7 investigational stage? 8 A. The New Drug Application was 9 pending. There were also -- I believe there were 10 also ongoing studies. 11 Q. Okay. Other than the two 12 problems that you just laid out that you called 13 attention to without offering solutions according 14 to Doctor Christensen, were there any other 15 reasons that Doctor Christensen gave you for why 16 you were not going to be promoted? 17 A. As I indicated, that's the 18 only specific comment that I recall. 19 Q. How about generally, did you 20 have an impression as to why you weren't going to 21 be -- other than what you've already told us, did 22 you have any other impressions as to why you were 23 not going to be promoted at Lilly? 24 A. No. Page 27 1 Q. Other than talking with Doctor 2 Christensen, can you recall any other reason that 3 you were either told or believed was the reason 4 why you were not going to get promoted? 5 A. I don't really know why I 6 wasn't promoted, obviously others were deemed 7 more competent. 8 Q. More competent at what? 9 A. I don't know. 10 Q. When you were there for the, 11 was it, approximately four and a half years at 12 Lilly, were other people promoted past you into 13 positions that you thought you should be promoted 14 to, in other words was there somebody on your 15 level or below you that was promoted past you or 16 in lieu of you? 17 A. I paused because your question 18 said four and a half years, and that doesn't -- 19 it was late '81. It was closer to three and a 20 half years. 21 Q. Okay. Well, during the time 22 you were at Lilly, after this, after you came to 23 the realization that you were not going to be 24 promoted, do you recall anybody else at Lilly Page 28 1 that was either on your level or below you that 2 was promoted in a position that you thought you 3 should have been promoted to? 4 A. Doctor Zerbe was made director 5 of the neuropharmacology area. I didn't know -- 6 I don't recall where Doctor Zerbe had been 7 working within Lilly. 8 Q. Was he under your supervision 9 at all? 10 A. No. 11 Q. How about Max Talbott, when 12 did Doctor Talbott start working at Lilly, if you 13 know? 14 A. About the same time I did. 15 Q. Were you his superior? 16 A. I beg your pardon? 17 Q. Were you Doctor Talbott's 18 superior while you were at Lilly? 19 A. No. 20 Q. Were you on an equal level? 21 A. Yes. 22 Q. Tell me what your 23 responsibilities were when you first started at 24 Lilly? Page 29 1 A. In general, I was a liaison 2 between the company and the Food and Drug 3 Administration on certain assigned drugs. 4 Q. What drugs were those? 5 A. Fluoxetine was obviously one 6 of them, Nabilone was another, Pergolide was 7 another. There were some other investigational 8 drugs, some of which were never pursued; among 9 the marketed drugs, the various insulin products. 10 I saw some of the records on Darvon, but for 11 reasons related to my prior position, I could not 12 appear before FDA, and did not, as I recall, even 13 sign correspondence on Darvon. 14 Q. Because of a perceived 15 conflict of interest of some sort? 16 A. Yes. I reviewed advertising, 17 advised within the company on regulatory matters. 18 Q. When you say you reviewed 19 advertising, you mean Lilly product advertising? 20 A. Yes. 21 Q. Did you work on fluoxetine the 22 entire time you were with Lilly in some capacity 23 or another? 24 A. Yes. Page 30 1 Q. In your capacity as liaison 2 between Lilly and FDA, we know that you were 3 responsible for submitting correspondence and 4 other various documents to the FDA through your 5 position. What other responsibilities did you 6 have as liaison? 7 A. There would be, from time to 8 time, telephone calls between various FDA 9 personnel and myself, the contents of which were 10 of course shared with the relevant individuals at 11 Lilly. I arranged for a number of meetings at 12 FDA. 13 Q. Anything else? 14 A. I reviewed the intended 15 submissions, occasionally had suggestions within 16 the company for some revision, and in the case of 17 fluoxetine, I was in charge of preparing the New 18 Drug Application. 19 Q. Is Nabilone marketed? 20 A. It was marketed, I don't 21 really know whether it's currently marketed or 22 not. 23 Q. What type of a drug was 24 Nabilone or is Nabilone? Page 31 1 A. Nabilone is closely related 2 chemically and pharmacologically to, at the time, 3 tetrahydrocannabinol. It was intended for use in 4 relieving the nausea and vomiting associated with 5 chemotheraphy. 6 Q. Other than problems you saw 7 with record keeping and the disposition of 8 investigational drug supplies, and records at 9 Wishard Hospital, do you have any other 10 criticisms with regards to the company's 11 developing and testing of fluoxetine? 12 MR. FREEMAN: The question seems to 13 indicate that the witness had said something with 14 respect to -- 15 MS. ZETTLER: You're right, Joe, I'm 16 sorry, let me ask it again. 17 Q. You have testified that you 18 had voiced criticisms to Doctor Christensen about 19 records that were kept at Wishard, and records 20 regarding the disposition of investigational 21 drugs, although you did not recall whether or not 22 those criticisms were directed towards 23 fluoxetine. Do you have or do you recall any 24 criticisms that you had with the way that Lilly Page 32 1 was developing fluoxetine or testing fluoxetine 2 or anything with regards to the aspects of 3 fluoxetine whatsoever? 4 A. I was concerned about the 5 magnitude of studies in Europe and our capacity 6 to deal with the enormous amount of incoming 7 data. 8 Q. Anything else? 9 A. Not that I can recall now. 10 Q. How about reporting the 11 adverse events, do you have any criticism with 12 regards to either the way the adverse events 13 related to fluoxetine were reported or any 14 investigation that was done with regards to 15 adverse events, limited to fluoxetine? 16 A. With one exception. That was -- 17 the one exception was, in my opinion, 18 satisfactorily resolved. I recall one incident, 19 but I do not recall all of the details of this, 20 where an older patient -- at the time I thought 21 she was elderly, but over the years I think maybe 22 she wasn't so elderly -- 23 MR. FREEMAN: She's getting younger 24 every day. Page 33 1 A. -- who received fluoxetine and 2 developed a skin rash. I don't recall why I took 3 a particular interest in that case, but I asked 4 questions and requested all available documents, 5 correspondence, et cetera, and concluded that 6 that incident had been quite severe, possibly 7 life-threatening. It was then -- I'm sure once I 8 became aware of it, it was suitably reported 9 under the existing regulations, and was, to the 10 best of my recollection, specifically cited in 11 the first draft of the package insert. 12 Q. You said once you became aware 13 of it it was suitably reported. Did you have any 14 reason to believe that if you had not become 15 aware of it, it would not have been suitably 16 reported? 17 A. I think all I can say is that 18 I did not feel sure on that point. 19 Q. Had there been instances that 20 you were aware of in the past where Lilly had not 21 reported serious adverse events on a Lilly drug? 22 A. I was not aware of any failure 23 to report. 24 Q. Did you have some reason to Page 34 1 believe that they may not have reported the rash 2 if you hadn't become aware of it? 3 A. I don't know, I don't know 4 whether it would have been reported or not, other 5 than as a simple skin rash. 6 Q. So it may have been reported, 7 but not to the severity that you believe the 8 event had occurred? 9 A. Perhaps. 10 Q. Why is it that you believe 11 that or you feel that that would have been the 12 case if you had not become aware of it? 13 A. Again, the details are long 14 lost to memory. My recollection could well be 15 wrong, but it is that I had to make a specific 16 effort to inquire. 17 Q. About the adverse event? 18 A. Yes. 19 Q. Who did you have to make the 20 specific effort to inquire to? 21 A. Doctor Paul Stark. 22 Q. How did you become aware of 23 the adverse event, the rash adverse event, in the 24 first place? Page 35 1 A. I don't remember. As I 2 indicated, I don't know what prompted me to make 3 a special effort in that case. 4 Q. Do you recall approximately 5 when during your employment at Lilly this rash 6 incident occurred? 7 A. No. It was quite some months 8 before the New Drug Application was filed, and 9 actually I don't remember exactly when we filed 10 that. 11 Q. I believe it was September of 12 '83, does that ring a bell -- actually it was 13 September 6, 1983 to be exact. 14 A. I was sure you would know. I 15 certainly have no reason to dispute that. 16 Q. The incident with the rash 17 adverse event occurred prior to the New Drug 18 Application being filed, correct? 19 A. I believe so. 20 Q. Do you have an opinion or did 21 you have the impression that Lilly under-reported 22 the severity of adverse events that occurred on 23 their clinical trials on fluoxetine? 24 A. No -- I mean yes, I have an Page 36 1 opinion, and I do not believe that they 2 systematically engaged in any such practice. 3 Q. How about periodically? 4 A. Or periodically. 5 Q. Did you have a specific 6 discussion with Doctor Stark about this adverse 7 event, the rash? 8 A. That's a reasonable 9 assumption, but I have no specific memory of 10 that. 11 Q. Do you recall in general 12 discussing the issue with Doctor Stark, raising 13 it with him? 14 A. I can't really recall anything 15 more than I've already described. 16 Q. What was Doctor Stark's 17 position at that time, if you recall? 18 A. He was the clinical monitor on 19 fluoxetine. 20 Q. In your position at Lilly, did 21 you ever have responsibility to review clinical 22 report forms for any particular fluoxetine study? 23 A. Would you clarify your term 24 clinical report forms? Page 37 1 Q. The forms that were used by 2 the clinical investigators during clinical 3 trials. 4 A. Oh. I had always called them 5 case report forms. 6 Q. Okay. 7 A. But your question, as I 8 understand it, is did I ever review them, yes. 9 Q. For what reason? 10 A. Clarification, accuracy. 11 Q. How about for clarity or 12 consistency, why don't we call them CRFs? 13 A. Very well. 14 Q. Earlier you testified that you 15 were concerned about the magnitude of the studies 16 in Europe, and the firm's capacity to deal with 17 an enormous amount of incoming data, correct? 18 A. Yes. 19 Q. And that's specifically on the 20 fluoxetine trials, correct? 21 A. Yes. 22 Q. What was it about Lilly's 23 ability to deal with the amount of data coming in 24 from the foreign trials that concerned you, for Page 38 1 instance, not enough personnel, not enough 2 computer capacity, things of that nature? 3 A. I questioned whether we had 4 enough personnel. 5 Q. When you started at Lilly, how 6 many clinical trials on fluoxetine were being run 7 outside the United States? 8 A. I have -- at this date, I 9 really have no idea. 10 Q. Was there information coming 11 in from outside the United States on clinical 12 trials that were being run by Lilly on fluoxetine 13 when you first started? 14 A. I'm very uncertain on this 15 point. I don't think so. When I first started, 16 the amount of data incoming from Europe gradually 17 increased, I can't be more specific than that. 18 Q. Back then when you first 19 started with Lilly, do you recall what the FDA 20 requirements were with regards to reporting of 21 clinical trials being conducted outside the 22 United States by drug companies? 23 A. Information derived from 24 studies conducted overseas, which was available Page 39 1 to Eli Lilly, was required to be reported to the 2 FDA. 3 Q. Would Lilly have to get, for 4 instance, approval by the FDA for protocols of 5 trials they were going to run outside the United 6 States on fluoxetine? 7 A. If the investigational drug 8 itself was sourced from within the United States, 9 yes. 10 Q. When you say if the 11 investigational drug itself was sourced from 12 within the United States, what do you mean? 13 A. If the drug was shipped from 14 Indianapolis to, for example, London. 15 Q. To your knowledge, did Lilly 16 have sources outside the United States at that 17 time where they were manufacturing clinical trial 18 materials for fluoxetine trials? 19 A. I'm not sure of that, I really 20 don't remember that. 21 Q. Do you recall submitting 22 protocols to the FDA for approval that were to be 23 conducted outside the United States on 24 fluoxetine? Page 40 1 A. I'm not sure, but I would take 2 exception to one aspect of the question. Other 3 than the initial protocol, when an IND was filed 4 specific approval of a protocol was not required. 5 Q. Okay. So the core protocol, 6 as they say, needed to be approved by the FDA, 7 but protocols that were patterned after that 8 would not have to be approved? 9 A. I'm not quite sure what you 10 mean by core protocol. 11 Q. My understanding is -- and I'm 12 a little bit confused on this so bear with me, 13 okay. My understanding is that protocols that 14 are run on studies done in the United States were 15 submitted to the FDA for approval before studies 16 could be conducted. 17 A. That isn't correct, or was not 18 then. 19 Q. Okay. 20 A. With the exception of the very 21 first study to be conducted under a new IND. 22 Q. When you say the very first 23 study, you mean the very first study on humans? 24 A. That's correct. Page 41 1 Q. To your knowledge, was that 2 protocol submitted before you became employed by 3 Lilly? 4 A. Yes. 5 Q. Aside from the very first 6 protocol being submitted for approval by the FDA, 7 can you think of any other reasons a protocol 8 would have to be submitted to the FDA while you 9 were there at Lilly? 10 A. From time to time, the FDA, 11 for one reason or another, would require 12 submission of a specific protocol. In addition, 13 it was sometimes to the company's advantage to 14 submit a protocol for review and comment, 15 particularly for those multi-center studies that 16 were deemed particularly important. 17 Q. Like something that the 18 company would be thinking of using as a pivotal 19 trial later on? 20 A. Correct. 21 Q. Are you familiar with protocol 22 twenty-seven on fluoxetine? 23 A. I'm sure I was in the early 24 1980s, but I am not now. Page 42 1 Q. Do you recall a multi-center 2 study run on fluoxetine comparing fluoxetine, 3 placebo and imipramine? 4 A. I recall that there was such a 5 study. 6 Q. Do you recall whether or not 7 you submitted a protocol for that study while you 8 were working at Lilly? 9 A. I don't know whether that was 10 submitted prior to my going there or whether I 11 submitted it. 12 Q. How about final reports on 13 studies done outside the United States, if Lilly 14 runs a trial outside the United States and the 15 drug is sourced from within the United States, 16 did the FDA require that final reports on those 17 studies be submitted? 18 A. It's my recollection that the 19 final report had to be submitted regardless of 20 source, sourcing of investigational drug, that 21 is. 22 Q. Okay. So even if, for 23 instance, the fluoxetine used in the UK was 24 manufactured in London, the final reports on Page 43 1 those studies would still have to be submitted to 2 the FDA as far as you recall? 3 A. Yes. 4 Q. To your knowledge, did that 5 regulation ever change? 6 A. There were several changes in 7 the regulations while I was still at Lilly, I 8 don't recall the exact circumstances. It's my 9 best recollection that reports such as you 10 indicated would be -- would have to be submitted 11 under prior regulations or the revised 12 regulations. 13 Q. Do you recall submitting final 14 reports on foreign studies to the FDA while you 15 were at Lilly? 16 A. Not specifically. 17 Q. How about generally? 18 A. I beg your pardon? 19 Q. How about generally, do you 20 recall no specific final report, but do you 21 recall submitting final reports for studies done 22 outside the United States to the FDA? 23 A. I think I probably did, but I 24 simply can't remember. Page 44 1 Q. In your capacity as -- I know 2 I'm going to mess this up, so I'm going to look 3 at my notes. Give me what your position at Lilly 4 was again? 5 A. Medical advisor, clinical 6 research and regulatory affairs. 7 Q. Why don't we go -- can we 8 agree to say medical advisor to shorten it up? 9 A. Certainly. 10 Q. In your position as medical 11 advisor at Lilly, did you have any responsibility 12 with foreign regulatory submissions? 13 A. Indirectly. 14 Q. What were those 15 responsibilities? 16 A. I specifically recall one trip 17 made to London and to our UK affiliate offices. 18 The exact location was outside of London, and I 19 cannot remember the name of it. 20 MR. FREEMAN: Basingstoke? 21 A. Basingstoke, thank you. Where 22 certain individuals from Indianapolis met with 23 Lilly people from various countries. I recall 24 that we took with us multiple copies for Page 45 1 distribution and discussion of a summary that had 2 been prepared to be included in the NDA, and we 3 used the same summary for discussion purposes 4 with Lilly people from other countries, and 5 therefore who would be contacting other 6 regulatory bodies. 7 Q. Was that the interpretive 8 summary, the NDA interpretive summary, does that 9 ring a bell? 10 A. It had a title, I don't 11 remember what it was. I seem to remember that it 12 was supposed to be roughly one hundred pages. 13 Q. And this meeting was strictly 14 between Lilly employees either from Indianapolis 15 or the other affiliates? 16 A. Yes. 17 Q. Who went on that trip with you 18 from Indianapolis? 19 A. Mrs. Earlene Ashbrook I 20 specifically remember, Mr. Halk, whose last name 21 I cannot spell, sorry. There were others, and 22 I'm not sure now who. 23 Q. How about Doctor Stark, did he 24 go? Page 46 1 A. I really can't remember. 2 Q. How about Doctor Zerbe? 3 A. I don't think so. 4 Q. How about Doctor Talbott? 5 A. No, Doctor Talbott wouldn't 6 have been there, I don't think. 7 Q. Okay. Other than the meeting 8 that you attended over in Basingstoke with 9 members from Indianapolis and the other 10 affiliates, did you have any other responsibility 11 with regards to regulatory submissions made on 12 fluoxetine, other countries? 13 A. From time to time we, or I, 14 tried to advise or tried to supply requested 15 materials, but I have no recollection beyond 16 that. 17 Q. Okay. 18 MS. ZETTLER: Let's take a break. 19 (A SHORT RECESS WAS TAKEN.) 20 Q. Let's go back a little bit. 21 Can you give me your educational background after 22 high school? 23 A. My undergraduate education was 24 at Duke University, 1945 to 1948, BS degree in Page 47 1 chemistry; 1948 to 1950, MS degree in 2 biochemistry at Emory; 1952 to 1956, medical 3 school, George Washington University in 4 Washington, minus the sophomore year, which I 5 took at Emory. 6 Q. So you went back to Emory for 7 your sophomore year? 8 A. Yes. 9 Q. I'm sorry, go ahead. 10 A. Rotating internship at St. 11 Elizabeth's Hospital, July '56, end of June of 12 '57; residency in psychiatry at Duke University 13 in 1957 to 1960. 14 MR. FREEMAN: What university was 15 that? 16 THE WITNESS: Duke University. 17 A. And the last four months of my 18 residency, back at St. Elizabeth's. That would 19 have been July 1, 1960 to the end of October of 20 1960. 21 Q. Okay. Any other graduate 22 degrees that you received besides your M.D.? 23 A. Well, master's. 24 Q. Any other besides that? Page 48 1 A. No. 2 Q. What did you do after you 3 completed your residency in October of 1960? 4 A. I was appointed to the staff 5 at St. Elizabeth's, assigned to maximum security -- 6 Q. How long did you do that? 7 A. -- and later was made 8 assistant chief, maximum security. Until the end 9 of 1964. 10 Q. And then you went to the FDA? 11 A. That's right. 12 Q. Are you Board certified? 13 A. Yes. 14 Q. When were you Board certified? 15 A. Roughly, 1963. 16 Q. In what specialty? 17 A. Well, the Board is the 18 American Board of Psychiatry and Neurology, I was 19 certified in psychiatry. 20 Q. Have you ever practiced as a 21 neurologist? 22 A. No. 23 Q. While you were at St. 24 Elizabeth's Hospital, did you ever conduct Page 49 1 clinical trials on psychotropic drugs? 2 A. No. 3 Q. Have you ever conducted a 4 clinical trial on any drug other than being a 5 monitor for a drug company? 6 A. Two or three occasions at 7 Abbott on relatively minor products. I actually 8 designed and supervised a study of Selson Blue 9 shampoo. I might add the gratuitous comment that 10 I don't regard that as the pinnacle of my career. 11 MR. SMITH: It involves the head, 12 though, doesn't it, Doctor? 13 THE WITNESS: I beg your pardon? 14 MR. SMITH: It involves the head. 15 THE WITNESS: That's right. 16 A. And I literally conducted a 17 few very small-scale studies within Abbott using 18 volunteers on some eye drop formulations. And I 19 think there was another study on a psoriasis -- 20 potential psoriasis product that died a fairly 21 rapid death. 22 Q. Okay. Any prescription 23 medications? 24 A. I beg your pardon? Page 50 1 Q. Any prescription medications 2 that you've run clinical trials on? 3 A. Oh, I take it back, I'm 4 forgetting. I designed one or two studies on 5 Hepatitis B, immune globulin. 6 Q. Outside working for a drug 7 company, have you ever been involved in a 8 clinical trial on any medication whatsoever? 9 A. No. 10 Q. Since you left Lilly, what 11 have you been doing employment wise? 12 A. Starting in June, 1985 I went 13 to work as a staff psychiatrist at Anneewakee, 14 and I'll go ahead and spell that, 15 A-N-N-E-E-W-A-K-E-E. Anneewakee was a 16 residential treatment center for adolescent 17 patients. 18 Q. How long were you there? 19 A. Until January, 1987. 20 Q. And what did you do after 21 that? 22 A. There was a brief period when 23 I was not working, my mother was terminally ill. 24 On April 1st, 1987, I went to work at Brynnmarr, Page 51 1 B-R-Y-N-N-M-A-R-R, Hospital in Jacksonville, 2 North Carolina, working primarily, but not 3 exclusively, in the adolescent area which I later 4 headed up. 5 Q. Okay. And how long were you 6 at Brynnmarr? 7 A. Initially I went there simply 8 on a temporary basis for two to three months, and 9 I stayed about two and a half months and went 10 back to Atlanta endeavoring to build a home. 11 Looked around, nothing appealed to me that I 12 became aware of, and I returned to Brynnmarr for 13 another stretch, and later left and returned for 14 another stretch, which added up to about two plus 15 years. I left in a little over two years, I left 16 in June, 1989. 17 Q. In those periods of time that 18 you had left Brynnmarr, were you working at other 19 places? 20 A. Very, very briefly. I 21 accepted a position at the Center for Psychiatry 22 in Atlanta. 23 Q. Did you ever actually work at 24 the center? Page 52 1 A. I think my total tenure there 2 was ten days. 3 Q. Why so short? 4 A. I guess one might say I was 5 displeased. The pressure was there for me to 6 essentially play salesman, which I did not 7 perceive to be a role I cared for. And in 8 addition, I thought there was pressure to 9 hospitalize patients. 10 Q. When you say pressure to play 11 salesman, you mean to recruit patients? 12 A. No, to call on physicians. 13 Q. To call on physicians? 14 A. Yes. 15 Q. In what capacity? 16 A. As a representative for the 17 large group practice. 18 Q. When you say call on 19 physicians, you mean like general practice 20 physicians or other psychiatric professionals? 21 A. General practice physicians, 22 internists, others. In addition, I had specified 23 in interviews that I preferred to work in one 24 location or at least on a given day, be at one Page 53 1 location, and I was being told to apply for staff 2 privileges at various hospitals scattered all 3 over the Atlanta metropolitan area. It was 4 rapidly apparent then that this was not going to 5 be satisfactory and I resigned. 6 Q. Any other positions that you 7 held in the times you took off from working at 8 Brynnmarr Hospital? 9 A. No. 10 Q. What did you do after that? 11 A. I retired. 12 Q. Are you currently retired? 13 A. No. 14 Q. How long were you retired? 15 A. Until February 21st of this 16 year. 17 Q. And now what are you doing? 18 A. I'm working part time as a 19 psychiatrist at Graydon Manor, G-R-A-Y-D-O-N, in 20 Leesburg, Virginia. 21 Q. And have you been working part 22 time at Graydon since February 21st of '94? 23 A. Yes. 24 Q. Any other positions that you Page 54 1 currently hold? 2 A. No. Let me go back a moment 3 again in the interest of total accuracy. During 4 the time that I was retired, I saw an occasional 5 patient, including the young lady I mentioned who 6 was studying to be a court reporter, and did some 7 consulting work on one occasion that related to 8 the deposition that I previously mentioned in 9 earlier testimony. 10 Q. Throughout your practice, 11 Doctor, have you ever prescribed Prozac to your 12 patients? 13 A. Yes. 14 Q. On how many occasions would 15 you say you prescribed Prozac? 16 A. Perhaps twelve, fifteen, I 17 don't know exactly. 18 Q. Less than twenty? 19 A. Yes, I believe so. 20 Q. Have you prescribed Prozac to 21 adolescents? 22 A. Yes. 23 Q. On how many occasions? 24 A. Perhaps five or six, most of Page 55 1 whom were already receiving Prozac on the order 2 of a physician who was responsible for that 3 particular patient prior to transfer of 4 responsibilities. 5 Q. Do you feel comfortable 6 prescribing Prozac to adolescents? 7 A. Yes. 8 Q. Have you ever had a patient 9 who has experienced an adverse reaction on 10 Prozac? 11 A. Not of any clinical 12 importance. 13 Q. Have you prescribed other 14 medications concomitantly with Prozac to those 15 people that you prescribed Prozac to? 16 A. Yes. 17 Q. What types of medications? 18 A. An antipsychotic. Otherwise, 19 I don't offhand recall. 20 Q. What prompted you to prescribe 21 a concomitant antipsychotic with Prozac in that 22 patient? 23 A. As I recall that, the 24 antipsychotic had been started shortly prior to Page 56 1 my first seeing the patient, and of course the 2 reason for prescribing the antipsychotic in the 3 first place was because the patient was 4 psychotic. 5 Q. That makes sense. 6 MR. SMITH: Was that a court reporter? 7 THE WITNESS: No, no, no. 8 Q. So it's your recollection that 9 the patient was already on the antipsychotic 10 medication when you began prescribing Prozac to 11 he or she? 12 A. Yes, but I have continued both 13 Prozac and the antipsychotic. 14 Q. How about any benzodiazepines, 15 have you ever concomitantly prescribed 16 benzodiazepines to patients on Prozac? 17 A. Not that I remember. I use 18 benzodiazepines very infrequently. 19 Q. How about any drugs with 20 sedative properties in conjunction with Prozac? 21 A. Well, of course an 22 antipsychotic agent does have typically some 23 sedative properties. I don't remember any other 24 instances. Page 57 1 Q. Have any of your patients who 2 you prescribed Prozac to experienced agitation 3 after beginning Prozac? 4 A. No. 5 Q. How about sedation? 6 A. No. 7 Q. Anxiety? 8 A. Not that I can remember 9 offhand. 10 Q. Irritability? 11 A. No, I don't think so. 12 Q. Akathisia? 13 A. No. 14 Q. Suicidal ideation? 15 A. Questionably in one patient 16 that I'm remembering. 17 Q. When you say questionably, do 18 you mean it was questionable whether or not that 19 person was actually suicidal? 20 A. Yes. 21 Q. What was your opinion, do you 22 feel that patient was suicidal? 23 A. No. 24 Q. How did the issue arise? Page 58 1 A. I'm not sure I quite 2 understand your question. 3 Q. Okay. Earlier you said it was 4 questionable whether or not a patient had become 5 suicidal while taking Prozac. How is it that the 6 question arose whether or not the person was 7 suicidal, is that something that they told you or 8 is that some behavior they manifested? 9 A. It was in the course of an 10 interview. 11 Q. Was this person on Prozac when 12 the interview took place? 13 A. Yes. If I might add, the 14 patient had rather vaguely expressed 15 approximately the same thoughts prior to my 16 starting. 17 Q. To the same extent? 18 A. I think so. 19 Q. Did you change your course of 20 treatment with regards to the Prozac after this 21 person voiced suicidal ideation? 22 A. I did discontinue the Prozac, 23 but not for that reason. 24 Q. Why did you discontinue the Page 59 1 Prozac? 2 A. I discontinued the Prozac 3 because while it had initially apparently been of 4 benefit, it no longer appeared to be the case. 5 Q. Why? 6 A. The gentleman initially had 7 not described a classical picture of major 8 depression, it was -- I was a bit uncertain when 9 I prescribed Prozac initially. He had described 10 mood swings, as did his significant other, and 11 when I took him off Prozac, I was less impressed 12 by depression and more impressed by mood swings, 13 particularly with an element of anger, and I 14 decided to discontinue the Prozac and initiate 15 Lithium. Again, there was initial benefit, and 16 then the patient ceased to come to the clinic, I 17 don't know why. 18 Q. Did this individual present 19 with anger and mood swings prior to starting the 20 Prozac? 21 A. Yes. 22 Q. Both anger and the mood 23 swings? 24 A. Yes. Page 60 1 Q. Did you see any exacerbation 2 of his mood swings and/or anger while he was on 3 the Prozac? 4 A. I don't know whether it was an 5 exacerbation or simply the way they were 6 described. I did not -- as I said, I did not 7 stop the Prozac for that reason, I stopped the 8 Prozac because I was more impressed with the 9 anger and less impressed by the depression. 10 Q. Generally in your patients who 11 you prescribe Prozac to, is that for depression? 12 A. Yes. 13 Q. Other than the patient who is 14 psychotic, were there any other -- and possibly 15 this other gentleman who may have been manic 16 depressive -- 17 A. Uh -- 18 Q. -- or experiencing mood 19 swings. 20 A. I beg to differ, I do not 21 regard him as manic depressive. 22 Q. Okay. But the one suffering 23 from mood swings and anger, were there any other 24 patients who had psychiatric diagnoses other than Page 61 1 depression that you were treating Prozac with? 2 A. No. 3 Q. Do you consider Prozac an 4 activating or a sedating antidepressant? 5 A. I don't really consider it 6 either one. I'm aware that the possible side 7 effect profile includes nervousness, for example, 8 but I just don't think of it as activating. 9 Q. Do you consider it a stimulant 10 type drug? 11 A. No. 12 Q. Do you prescribe it for taking 13 in the morning or evenings or in the afternoons? 14 A. Morning. 15 Q. Why? 16 A. Because of the possibility of 17 nervousness and possible insomnia and because, 18 frankly, that's the way it's usually given, and I 19 have no desire to try to run a miniature clinical 20 trial and decide for myself whether that's really 21 necessary or not. It's also a -- it's my 22 impression that one has better compliance with 23 medications that are taken in the mornings. 24 Q. Do you -- what's the typical Page 62 1 dosage that you prescribe? 2 A. Twenty milligrams. 3 Q. Even in adolescent clients? 4 A. Yes. 5 Q. Have you ever prescribed less 6 than twenty milligrams? 7 A. I don't think so. 8 Q. Have you ever prescribed more? 9 A. I would have to correct that. 10 There was one lady for whom I had prescribed 11 Prozac whom I saw -- during the period when I was 12 mostly retired, and I did give her a lesser dose 13 after a while, more as a matter of tapering and 14 trying to evaluate. 15 Q. How many patients have you 16 seen as part of your private practice over the 17 years would you say, estimated? 18 A. I have never actually had a 19 private practice. 20 Q. Okay. What I meant was 21 outside the industry work. 22 A. In my clinical practice, the 23 numbers are really quite small. While I was at 24 Anneewakee, I would have twenty, thirty female Page 63 1 adolescent patients, and during the time at 2 Brynnmarr, I might have -- I had, finally, some 3 overall responsibility for the adolescent unit, 4 but I would personally have at a given time ten, 5 twelve patients. 6 Q. When would you say you first 7 started prescribing Prozac? 8 A. It was during the period when 9 I was retired. 10 Q. From end of June of '89? 11 A. Yes. 12 Q. How many patients would you 13 say you've seen since June of '89, roughly? 14 A. Between twenty and thirty. 15 Q. And how many of those patients 16 would you say are suffering from depression or 17 were suffering from depression when you were 18 seeing them? 19 A. Probably between a third and a 20 half. 21 Q. Would you prescribe Prozac to 22 somebody who was psychotic without prescribing an 23 antipsychotic medication? 24 A. No. Page 64 1 Q. Why not? 2 A. Because I would not be 3 treating everything that I should be treating. 4 Q. When you were at Lilly, had 5 they performed the open label study on 6 schizo-affective disorder patients with Prozac? 7 A. I don't think so. 8 Q. When you were at Lilly, were 9 you aware of any cases where persons being 10 treated for depression became psychotic while on 11 Prozac? 12 A. I have no specific memory of 13 that, it may well have happened. 14 Q. Are you familiar with Doctor 15 David Dunner? 16 A. The name rings a bell. 17 Q. Are you aware that one of 18 Doctor Dunner's patients on a clinical trial on 19 fluoxetine became psychotic while on fluoxetine? 20 A. If you're asking me if I 21 remember it, no, I do not. 22 Q. Has anybody ever told you that 23 Doctor Dunner felt that one of his patients on 24 fluoxetine that became psychotic became psychotic Page 65 1 because of the fluoxetine? 2 A. I don't know whether someone 3 told me that or not. 4 Q. Would that surprise you? 5 A. Particularly not in this 6 context. I have to assume that this must have 7 happened or you wouldn't be asking the question. 8 Q. Let me ask it again. Would it 9 surprise you that somebody who is being treated 10 with fluoxetine for depression became psychotic 11 or suffered from psychosis because of the 12 fluoxetine? 13 A. I have a great deal of 14 difficulty answering that question. 15 Q. Why? 16 A. Because of the implied 17 conclusion having to do with causation. 18 Q. Okay. If a case of psychosis 19 was causally related by a clinical investigator 20 studying fluoxetine, to the use of fluoxetine, in 21 your opinion should that case have been reported 22 in the package insert for fluoxetine? 23 A. Possibly, but I can't answer 24 with any certainty without actually considering Page 66 1 the exact circumstances. 2 (PLAINTIFFS' EXHIBIT NO. 1 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. Have you had a chance to read 6 through Exhibit No. 1, Doctor? 7 A. Yes. 8 Q. Have you seen this exhibit 9 before? 10 A. I don't remember whether I 11 have or not. 12 Q. Who is Gisele Soyez? 13 A. Gisele Soyez was a clinical 14 research associate on the -- assigned to the 15 fluoxetine project. 16 Q. Okay. Was it common for her 17 to send out 1639 reports or drafts of 1639s for 18 review by investigators? 19 A. I think it was. 20 Q. Okay. Before today, were you 21 aware that Doctor Dunner felt that this patient 22 participating in Protocol No. 27, out of 23 confusion and psychosis, was probably drug 24 related or probably related to the fluoxetine? Page 67 1 A. I don't remember whether I saw 2 this. 3 Q. In your opinion should this 4 incident have been included in the fluoxetine 5 package insert? 6 A. I don't have a firm opinion on 7 that right now. It's been a long time since I've 8 handled regulatory matters and drafted package 9 inserts. The fact that Doctor Dunner regarded 10 this as probably drug related would not be, in my 11 opinion, the deciding factor. 12 Q. Why not? 13 A. It was an opinion. There's no 14 possibility of deciding definitely whether 15 fluoxetine caused the apparently rather brief 16 episode or not. 17 Q. Well, the same could be said 18 about the rash that you fought to have included 19 in the package insert, could it not? 20 A. I can't recall all of the 21 circumstances on that one or of possibly similar 22 episodes to this at this time nor can I totally 23 reconstruct my thought processes. I felt 24 confident with respect to that rash that it had Page 68 1 been caused by fluoxetine, and I'm not sure that 2 I can logically entirely defend that opinion at 3 this late date. 4 Q. You're talking about one 5 incident of rash that you wanted included in the 6 package insert, correct? 7 MR. FREEMAN: She didn't say that, she 8 didn't say whether it was one or multiple. 9 Q. I believe you said there was 10 one specific incident of a woman, an elderly 11 woman, on fluoxetine where you had learned had 12 suffered a severe rash, correct? 13 A. Yes. 14 Q. And that you argued for 15 including that incident, that rash, in the 16 package insert, correct? 17 A. I don't know that I said that 18 I argued about it. I prepared much of the first 19 draft of the package insert, and as I recall I 20 was alone at the time, I had no one -- no reason 21 to argue the point. 22 Q. You wanted that rash reported 23 in the package insert, did you not, Doctor? 24 A. Yes. Page 69 1 Q. Okay. Were there other 2 incidents of similar rash that prompted you to 3 fight for this one incident being reported in the 4 package insert or was it a singular incident as 5 far as you know? 6 A. I don't recall that I fought. 7 There were two or three other skin problems 8 associated with fluoxetine administration. They 9 were not the same clinical picture and I don't 10 remember details of the others, nor, as I 11 explained previously, can I entirely account for 12 my memory of that particular patient. 13 Q. Doctor Dunner was treating 14 that patient that appeared to become psychotic 15 while on fluoxetine, correct? 16 A. I presume so, although the 17 areas that are blacked out suggested that perhaps 18 there was another physician involved as well. 19 Q. And if there was another 20 physician, that physician agreed with Doctor 21 Dunner that the psychotic episode was probably 22 drug related, correct? If you look at the second 23 page or the last page, the paragraph on the 24 bottom. Page 70 1 A. That -- it appears to be the 2 case that Doctor Dunner and some other individual 3 concluded that the episode was, quote, probably 4 drug related. 5 Q. What other information would 6 you have had to have had to determine whether or 7 not this event merited inclusion in the package 8 insert? 9 A. I really don't know at this 10 point. It's been a long time since I made such 11 decisions, and I made many of them. 12 Q. Were you the person 13 responsible for deciding what would be included 14 in the package insert as far as adverse events 15 and what would not? And I'm talking strictly 16 about fluoxetine. 17 A. Certainly I was not the only 18 such individual. 19 Q. Who else was responsible to 20 make those decisions? 21 A. Doctor Stark would have had 22 input, Doctor Thompson, Doctor Zerbe. 23 Q. When you say Doctor Thompson, 24 you mean Leigh Thompson? Page 71 1 A. Yes. 2 Q. Anybody else? 3 A. There probably were 4 individuals, but those are the only ones that 5 occur to me at the moment. 6 Q. How about Doctor Bergstram? 7 A. I can't at the moment recall a 8 Doctor Bergstram. 9 Q. How about Doctor Lemberger? 10 A. Doctor Lemberger would have 11 received copies of drafts of the package insert, 12 yes, and would have commented. 13 Q. Do you recall any discussions 14 on whether or not to include incidents of suicide 15 attempts in the initial package insert for 16 fluoxetine? 17 A. I don't recall any such 18 discussions. 19 Q. Do you recall incidents of 20 suicides occurring on fluoxetine trials prior to 21 the initial insert being submitted to the FDA for 22 review? 23 A. I know that there were reports 24 of suicide attempts in patients receiving Page 72 1 fluoxetine. I don't know, I don't recall whether 2 any had been actual suicides or not. I have a 3 vague recollection that there were indeed 4 discussions of such reports. 5 Q. In what context? 6 A. I really don't know how to 7 characterize the context, I mean there were 8 ongoing discussions of adverse reactions. 9 Q. If suicide attempts occurred 10 in the clinical trials prior to submitting the 11 original insert to the FDA for review, why would 12 they not be included in the adverse event 13 listing? 14 A. I really have no answer to 15 that question now. 16 Q. Do you feel that they should 17 have been included? 18 A. Probably in a similar manner 19 to statements that are included in the package 20 inserts for other antidepressants. I think some 21 of those mention the possibility of suicide. 22 Q. I'm not talking about the 23 general cautionary statements about depressed 24 people suffering from suicidal ideation, I'm Page 73 1 talking about listing of adverse events occurring 2 during the fluoxetine clinical trials, okay. If 3 those such adverse events occurred, suicidal 4 ideation, suicide attempts, completed suicide, 5 why would they not be included in a listing of 6 the adverse events that occurred during the 7 clinical trials on fluoxetine? 8 A. I don't know. 9 Q. Do you think they should have 10 been, if they occurred? 11 A. Probably. 12 Q. And you have no idea why they 13 would not have been? 14 A. After approximately eleven 15 years, no, I don't. 16 Q. Let's talk about that 17 suicidality cautionary statement that you brought 18 up a couple of seconds ago. To your knowledge 19 had anybody at Lilly ever lobbied for a stronger 20 statement with regards to patients who may be 21 suffering from suicidal ideation and the 22 administration of fluoxetine? 23 A. I don't remember anyone taking 24 that position. I can't say that it didn't Page 74 1 happen. 2 Q. How about you, did you feel 3 that a stronger statement should be included in 4 the package insert other than a precautionary 5 statement about people suffering from depression 6 becoming suicidal in general? 7 A. I don't know. 8 (DISCUSSION OFF THE RECORD.) 9 (PLAINTIFFS' EXHIBIT NO. 2 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.). 12 Q. Have you had a chance to 13 review Exhibit 2? 14 A. Yes, I have. 15 Q. Does this refresh your 16 recollection as to who Doctor Bergstram is or 17 was? 18 A. I still can't picture Doctor 19 Bergstram. Obviously he was involved with early 20 studies, matters of half-life metabolites, et 21 cetera, as was Carl DeSante. 22 Q. How about Doctor Lemberger, 23 who was Doctor Lemberger? 24 A. Doctor Lemberger was a Page 75 1 clinical pharmacologist who was generally in 2 charge of the Phase 1 clinical trials and 3 volunteers at Wishard. 4 Q. Exhibit 2 purports to be 5 Doctor Bergstram's and Doctor Lemberger's 6 comments on the package insert submitted to them -- 7 or draft of the package insert for fluoxetine 8 submitted to them by you, correct? 9 A. Yes. 10 Q. And they list, it looks like, 11 two pages of typewritten comments, and also 12 attach a copy of the draft of the package insert 13 with some handwritten comments, correct? 14 A. Yes. 15 Q. And the second page of the 16 typewritten comments, the third page of the 17 actual exhibit, at the bottom under the 18 precaution section, they seem to suggest adding a 19 statement that, quote, patients -- and I'm 20 reading from just the typewritten part, not the 21 corrected part, okay -- patients with suicidal 22 ideation should be considered for 23 hospitalization. Do you see that? 24 A. Yes. Page 76 1 Q. Do you recall that issue 2 coming up where Doctor Lemberger and/or Doctor 3 Bergstram felt that that statement should be 4 added to the package insert under the precaution 5 section? 6 A. I have no recollection of 7 this. I have a vague recollection of circulating 8 one or more drafts of the insert prior to 9 submission of the NDA and soliciting comments 10 from various areas, but I have no memory of that 11 specific issue. 12 Q. Okay. Do you recall there 13 having been meetings regarding what should be 14 included in the package insert for fluoxetine, 15 and I'm talking about intra-Lilly meetings? 16 A. It's a reasonable assumption 17 that there may have been such meetings, but I 18 don't remember any of them. 19 Q. If you go to page six of the 20 draft of the package insert itself, in the upper 21 left-hand corner. I know it's a little difficult 22 to read because the copy is bad, but it looks 23 like up here, the section where it has the 24 general -- Page 77 1 A. Excuse me, if I might. I gave 2 up, I couldn't read it. 3 Q. Okay. We'll see if we can get 4 through it together. It looks like a handwritten 5 note up by the precaution section, the general 6 wording on suicidality in depressed patients. Do 7 you see that? 8 A. I see the note. It's -- 9 without a great deal of effort, it's largely 10 illegible. 11 Q. My best reading of it -- to me 12 it appears it says should we not state that 13 patients with suicidal ideation should be 14 considered for hospitalized? 15 A. I think your reading is 16 probably correct. 17 Q. Okay. Again, do you recall 18 that issue being raised at any time with regards 19 to the package insert while you were an employee 20 of Lilly? 21 A. As I indicated previously, I 22 have a vague recollection of discussions of the 23 issue, not necessarily related specifically to 24 the preparation of the insert. Page 78 1 MR. FREEMAN: The issue being? 2 THE WITNESS: The issue being 3 occurrence of suicide attempts or possibly actual 4 suicides occurring in patients in clinical trials 5 who received fluoxetine or who received placebo 6 or who received other antidepressant agents. 7 Q. Is it your recollection that 8 in the outpatient double-blind controlled studies 9 patients who presented a serious risk of suicide 10 were excluded from the study? 11 A. I have no specific 12 recollection, but that is a -- that's almost an 13 expected exclusion criteria. 14 Q. Do you recall the issue of 15 whether or not suicidality was either caused or 16 exacerbated by fluoxetine being raised by any 17 entity other than people at Lilly in the time you 18 worked there? 19 MR. FREEMAN: Would you read that 20 question back, please? 21 (THE COURT REPORTER READ BACK THE 22 REQUESTED TESTIMONY.) 23 A. I have no recollection of that 24 occurring. Page 79 1 Q. Do you recall application 2 being made for marketing of fluoxetine in Germany 3 while you were working at Lilly? 4 A. I know that application was 5 made to various regulatory bodies. The exact 6 time sequence, I don't recall, and I have no 7 specific recollection from that period of time 8 about Germany, about an application in Germany. 9 Q. Do you recall providing data 10 to the German affiliate regarding 11 phospholipidosis, toxicology, or zimelidine 12 syndrome in using fluoxetine while you were at 13 Lilly? 14 A. I remember absolutely nothing 15 about phospholipidosis, and I didn't understand 16 the rest of your question. 17 (PLAINTIFFS' EXHIBIT NO. 3 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Have you had a chance to 21 review Exhibit 3, Doctor? 22 A. Yes. 23 Q. I noticed when you were 24 reading the last page of the exhibit that you Page 80 1 were kind of chuckling to yourself. Can you tell 2 me why that was? 3 A. I think it was a fleeting 4 smile more than a chuckle, but be that as it may, 5 that was occasioned by some comment that, at this 6 point, I don't totally understand, having to do 7 with difficulties with the eye and the lung. And 8 according to this statement the BGA wanted newer 9 techniques, for example biopsy, and I thought 10 biopsing the eye and the lung would be a bit 11 inappropriate. 12 Q. Have you seen this document 13 before, Doctor? 14 A. Possibly, I don't know. 15 Q. I understand that you're not 16 listed as a main recipient or on the CC list, but 17 do you recall being alerted to questions raised 18 by regulatory agencies outside the United States 19 regarding fluoxetine? 20 A. I think I probably was, I may 21 well have seen this Telex and others. But again, 22 I have no specific recollection of it. 23 Q. What position was Doctor Zerbe 24 in around this time, if you recall? Page 81 1 A. By that time, Doctor Zerbe 2 was, I think, probably the director of the neuro 3 or neuroendocrine drug section or division or 4 whatever it was being called. Contrary to my 5 earlier statement, I think probably Doctor Zerbe 6 would not have been on the London trip. 7 Q. Would not have been on the 8 London trip? 9 A. Right. 10 Q. When you say the London trip, 11 you mean your trip to London? 12 A. Correct. 13 Q. Would the concerns raised by 14 the German government, as reflected in this 15 exhibit, have been reported to the FDA to your 16 knowledge back then? 17 A. Probably not. 18 Q. Why not? 19 A. I don't recall that there was 20 any requirement within the regulations that 21 concerns as opposed to information be reported. 22 Q. Okay. What if analyses of 23 data were done by Lilly in response to these 24 concerns raised by the German government, if that Page 82 1 had been done would those analyses then have been 2 sent to the FDA? 3 MR. FREEMAN: You mean the response to 4 these questions? 5 MS. ZETTLER: Right. 6 A. Probably not, assuming that 7 the data being analyzed had been or was scheduled 8 to be appropriately submitted to FDA. 9 Q. How about safety data analyses 10 generally, was there a requirement by the FDA 11 that those types of analyses be submitted to the 12 FDA by the manufacturer? 13 MR. FREEMAN: Done in this country or 14 done abroad or where? Safety analyses obviously 15 in this country are supplied. 16 MS. ZETTLER: I'm going to object to 17 your coaching the witness by your questions, Joe. 18 MR. FREEMAN: If that's an objection, 19 you've got to state specifically what you're 20 talking about, not generally. 21 A. I'm sorry would you repeat 22 your question? 23 Q. Sure. We'll start -- if a 24 safety analysis is done by Lilly on a product Page 83 1 such as, say, fluoxetine, is there a requirement 2 by the FDA that that safety analysis be submitted 3 to the FDA? 4 MR. FREEMAN: Does your question 5 assume that the data has been submitted or not? 6 MS. ZETTLER: I'm talking about an 7 analysis of safety data. 8 MR. FREEMAN: First answer whether 9 data has been submitted to the FDA, then you can 10 answer it whether it has not been. 11 Q. Let me ask it this way, 12 Doctor: It's our understanding, okay, that in 13 response to these concerns raised by the BGA that 14 employees at Lilly, in particular Doctor 15 Wernicke, participated in the analysis of the 16 occurrence of suicide attempts and suicides on 17 clinical trials of fluoxetine for submission to 18 the BGA, okay. Would such a study have to be 19 submitted to the FDA, as far as you know? 20 A. The underlying data would 21 certainly have to be submitted to the FDA. 22 Whether the analysis would need to be submitted 23 to the FDA, I can't answer as a generality. And 24 again, it's been a long time since I dealt with Page 84 1 such questions. 2 Q. Okay. So the best that you 3 can recall, there is no requirement by the FDA 4 that the concerns of another regulatory agency 5 outside the United States be submitted to the 6 FDA, correct? 7 A. That is correct. 8 Q. And to the best of your 9 recollection there was no requirement, at least 10 while you were working there, that analyses done 11 in response to those concerns be submitted to the 12 FDA, correct? 13 A. That's the way I remember the 14 situation at that time, yes. 15 Q. Do you know what clinical 16 trial data was submitted to foreign regulatory 17 agencies outside the United States during the 18 time that you worked there? 19 A. I certainly don't know here in 20 July, 1994. I don't believe I would have known 21 in any detail in any way at that time. 22 Q. Would it essentially have been 23 the same clinical trial data that was submitted 24 to the FDA to your knowledge? Page 85 1 A. Probably, yes. 2 Q. Do you know a Doctor Von 3 Keitz? 4 A. The name seems very slightly 5 familiar, that's all I can add. 6 Q. Doctor Von Keitz -- or B. Von 7 Keitz, I'm not sure if it's actually a doctor -- 8 was from Bad Homburg, an affiliate. Does that 9 refresh your recollection at all? 10 A. No. 11 Q. Do you recall doing work on 12 the package insert to be submitted to the German 13 government on fluoxetine? 14 A. I would assume that said 15 package insert would have been submitted in 16 Germany. My knowledge of German is -- was never 17 better than fragmentary. 18 (PLAINTIFFS' EXHIBIT NO. 4 WAS 19 MARKED FOR IDENTIFICATION AND 20 RECEIVED IN EVIDENCE.) 21 Q. Have you had a chance to 22 review Exhibit 4? 23 A. Yes. 24 Q. Does this refresh your Page 86 1 recollection as to whether or not you were 2 involved in work on the German package insert for 3 fluoxetine? 4 A. Obviously from this document I 5 had some involvement, but I really doesn't 6 remember it. 7 Q. Okay. When you were at Lilly, 8 did Lilly know that it was dangerous to prescribe 9 fluoxetine concomitantly with MAO inhibitors? 10 A. I was -- going back to FDA 11 days, I was aware that antidepressants in 12 general, not of the monoamine oxidase inhibitor 13 type, and concurrent administration of monoamine 14 oxidase inhibitor had been reported to be 15 associated with very serious reactions. 16 Q. I'm talking about -- 17 A. I realize you're trying to 18 address fluoxetine, and I'm trying to remember. 19 I'm sorry, I interrupted you. 20 Q. No, I interrupted you, I'm 21 sorry. Do you recall specifically while you were 22 at Lilly the knowledge that it was dangerous to 23 prescribe MAO inhibitors in conjunction with 24 fluoxetine specifically? Page 87 1 A. I have no memory of 2 discussions or who recognized what in that 3 regard. 4 Q. Look at the third page of 5 Exhibit No. 4. 6 MR. FREEMAN: Why don't you explain 7 what Exhibit No. 4 is. 8 Q. Exhibit No. 4 purports to be a 9 copy of the package insert to be submitted to the 10 BGA, a cover letter dated January 5, 1984 11 directed to you by B.V. Keitz, K-E-I-T-Z, of Bad 12 Homburg, correct? 13 A. Yes. 14 Q. On the third page of the 15 exhibit or the second page of the package insert 16 draft, whichever you prefer, under interactions 17 with other substances, it says TM, which I assume 18 means whatever the trademark name for fluoxetine 19 would have been in Germany, should not be taken 20 concomitantly with certain drugs which are used 21 in depressive conditions, so-called MAO 22 inhibitors. MAO inhibitors should be 23 discontinued at least two weeks before start of 24 treatment with trademark, correct? Page 88 1 A. That's what it says, yes. 2 Q. To your knowledge was there 3 specific evidence that had been obtained by Lilly 4 to that point, that there could be an adverse 5 drug reaction if you combined MAO inhibitors and 6 fluoxetine? 7 A. To the best of my 8 recollection, we had no specific information 9 about fluoxetine and an interaction with 10 monoamine oxidase inhibitors. 11 Q. The general assumption was 12 just made that it wasn't advisable to combine the 13 two? 14 A. The presumption was that -- 15 yes, that there might be a hazard there, and it 16 would be a difficult question to study in human 17 beings. 18 Q. To your knowledge were those 19 studies ever done? 20 A. To my knowledge, no. 21 Q. To your knowledge were any 22 studies on the issue done in animals? 23 A. I don't know, I don't know. 24 Q. What was your complaint Page 89 1 regarding the record keeping on disposition of 2 investigational drugs and supplies that we talked 3 about earlier? 4 A. As I recall, it was very 5 difficult to account for exactly how much of an 6 investigational drug was present, exactly how 7 much had been supplied to whom, and for what 8 purpose, for example, a specific study protocol, 9 how much had been actually used in the study, how 10 much, if any, had been destroyed or how much had 11 been returned. Records, as I recall, were 12 handwritten and not always complete. 13 Q. And you discovered this during 14 your audit of documents that Doctor Christensen 15 asked you to do or is that with the Wishard 16 facility only? 17 A. No, those were two separate 18 issues as I remember them. It seems to me I 19 stumbled into the question of record keeping on 20 investigational drug supplies, something prompted 21 me to ask what had seemed a routine question, and 22 I was, I guess, surprised that this was not a 23 computerized function. I had asked something 24 about a drug shipment to some investigator, and Page 90 1 the exact details were difficult to retrieve. 2 Q. Did Lilly at that time, in 3 your opinion, have the capability to computerize 4 such information? 5 A. Yes. 6 Q. When you were with Lilly, did 7 they have a system for computerizing information 8 on adverse events occurring either post-marketing 9 for a drug or during clinical trials? 10 A. Yes. 11 Q. What, if anything, was done to 12 rectify the problem that you saw with the record 13 keeping on disposition of investigational drug 14 supplies? 15 A. I really don't remember. 16 Q. How about the documents, the 17 records that you audited at Wishard Clinic, what 18 were your concerns about those records? 19 A. I can't remember specifically -- 20 with one exception, I can't remember 21 specifically. There had been a statement 22 somewhere to the effect that a certain study on -- 23 study of Nabilone in normal volunteers had been 24 conducted under double-blind conditions, and some Page 91 1 notations led me to think that that might not 2 have been the case, and I discussed the matter 3 with Doctor Lemberger who acknowledged that at 4 least in some part of the study he was aware of 5 the drug being administered. That was not the 6 total finding, but I can't remember any further 7 details. 8 Q. How would it be that Doctor 9 Lemberger would become aware of what drug was 10 being administered if the study was supposed to 11 be blinded? 12 A. I don't know. 13 Q. To your knowledge has there 14 been an inappropriate breaking of the blind in 15 fluoxetine trials that were conducted while you 16 were at Lilly or before you came on? 17 A. I have no memory of any, as 18 you say, inappropriate breaking of the blind. I 19 have no memory, for that matter, of appropriate 20 breaking of the blind, but I'm sure that 21 occurred. 22 Q. Why do you say that? 23 A. In any large scale clinical 24 study, a few patients will have some event in Page 92 1 their lives, it might even be the need, say, for 2 elective surgery, when it would be important to 3 know what drug they had been taking. That would 4 be an example of an appropriate breaking of the 5 blind and I don't know that that specific thing 6 occurred, but some such circumstances undoubtedly 7 arose. I don't remember them, and I don't 8 remember any occurrence of an inappropriate 9 breaking of the blind. 10 MS. ZETTLER: Okay. Let's take a 11 lunch break. 12 (A LUNCH BREAK WAS TAKEN.) 13 BY MS. ZETTLER: 14 Q. Did Doctor Leigh Thompson 15 start working for Lilly before or after you 16 started working there? 17 A. After. 18 Q. About how long after you 19 started working there? 20 MR. FREEMAN: Read the question back, 21 I misunderstood. 22 MS. ZETTLER: How long after she 23 started working there did he start working there. 24 A. I don't really remember, I Page 93 1 can't -- one of the exhibits puzzled me because I 2 couldn't straighten out the chronology and I just 3 don't remember. 4 Q. Which exhibit, do you know? 5 A. Exhibit 2. 6 Q. Did you expect him to be 7 listed on here if he was working there at that 8 time? 9 A. Yes. Also Doctor Zerbe. 10 Q. What was Doctor Thompson's 11 position when you first started with Lilly? 12 A. I don't remember the title; he 13 was in charge of clinical research for Lilly 14 research laboratories. 15 Q. Was he your superior? 16 A. Yes. Or if not initially, 17 shortly thereafter. 18 Q. Did you report to him? 19 A. Yes. 20 Q. Do you recall a time when the 21 FDA questioned Lilly's practice of breaking the 22 blind on fluoxetine trials to transition patients 23 into an open-label phase of the trials? 24 A. I have a very vague Page 94 1 recollection of that question coming up. 2 Q. What is your recollection of 3 that? 4 A. I can't add anything really to 5 your question. 6 Q. When you wrote letters to the 7 FDA, did you always draft those letters yourself 8 or did somebody else draft them for you, for your 9 signature, on fluoxetine? 10 A. For the most part, I drafted 11 them myself. 12 Q. Can you recall any situations 13 where you would not have drafted a letter to the 14 FDA that was sent over your signature? 15 A. If it had been a very routine 16 submission, I probably would have simply asked my 17 secretary to send this in with kind of form 18 language. 19 Q. Do you recall being a member 20 of the clinical projects review committee? 21 A. I don't recall the clinical 22 projects review committee, I'm sorry. 23 Q. Do you recall being a member 24 of any specific committee at Eli Lilly regarding Page 95 1 fluoxetine? 2 A. No. 3 (PLAINTIFFS' EXHIBIT NO. 5 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to 7 review Exhibit 5? 8 A. Yes. 9 Q. Do you recall this exhibit? 10 A. No. 11 Q. It purports to be minutes or 12 notes from a clinical projects review committee 13 meeting dated October 4, 1983, correct? 14 A. Yes. 15 Q. And you're listed as an 16 additional recipient? 17 A. Yes. 18 Q. On the first page of the notes -- 19 of the minutes themselves, it talks about point 20 number four, weekly dosing study. Do you see 21 that? 22 A. Yes. 23 Q. Do you recall if that study 24 was ever conducted? Page 96 1 A. I think it probably was not. 2 I have a vague recollection of the suggestion and 3 I don't know what happened; I think it was not. 4 Q. What was the theory behind 5 that study, if you recall? 6 A. I think the idea was that 7 fluoxetine and the desmethyl metabolite both had 8 a long half-life, and that once a patient reached 9 steady state, it would be theoretically possible 10 to give a dose once a week and maintain the 11 steady state. 12 Q. Why is it that you feel that 13 study was not done? 14 A. Assuming that it was in fact 15 not conducted, I don't know why that would have 16 been done. Why do I say it probably wasn't 17 conducted, mostly because I can't remember. 18 Q. Do you know Doctor Stuart 19 Montgomery? 20 A. Not offhand. 21 Q. At the bottom of the page, it 22 says there's been a retrospective review of the 23 fluoxetine NDA data base with respect to the 24 zimelidine-like symptoms. Do you see that? Page 97 1 A. Yes. 2 Q. Did you work on that issue, 3 whether or not zimelidine-like symptoms are 4 related to the use of fluoxetine? 5 A. I think so. Although at this 6 point in time, I couldn't name the, quote, 7 zimelidine-like symptoms. It seems to me they 8 were similar to flu. Beyond that, I can't go. 9 Q. Do you know whether or not 10 there were people who suffered zimelidine-like 11 syndrome who were taking fluoxetine during the 12 clinical trials? 13 A. To the best of my 14 recollection, we searched the data base for 15 anyone on whom the occurrence of three, four, 16 five, six symptoms had ever been reported. I 17 think fever may have been one of them. I think 18 we probably searched the data base using the same 19 search parameters for patients in placebo groups 20 and other agents. And my best recollection is 21 that the bottom line, if one can excuse that 22 term, was that we probably had no -- that 23 fluoxetine probably had no, quote, zimelidine, 24 quote -- or hyphen, like, symptoms. Obviously in Page 98 1 a population of hundreds and hundreds of 2 patients, there would be some who had -- that had 3 the flu, who had had fever or who had had 4 whatever the other symptoms were that we 5 researched for. The numbers were fairly small. 6 Of course I don't know what they were exactly and 7 there was just nothing unusual about it. I think 8 we concluded that somehow, probably by comparing 9 to the other drugs, that we probably did not have 10 the zimelidine problem. 11 Q. Okay. On the next page of the 12 exhibit, under point number nine, it says CPR 13 recognizes that fluoxetine will need careful 14 post-marketing surveillance in the first ten 15 thousand patients. Do you see that? 16 A. Yes. 17 Q. Do you recall if that was 18 done? 19 A. I would have had no knowledge 20 of post-marketing surveillance since I was 21 working in North Carolina at the time. 22 Q. Before you left was the drug 23 approved in any countries outside the United 24 States, as far as you recall? Page 99 1 A. I really don't remember. 2 Q. Do you recall that it was felt 3 that post-marketing surveillance on the first ten 4 thousand patients would be necessary after you 5 were there? 6 A. I think that was a proposal 7 from, I think, Doctor Thompson. 8 Q. Well, Doctor Thompson actually 9 proposed a study, did he not, at first? 10 A. I don't know, he may have. 11 Q. If you will look at the next 12 page, it talks about special fluoxetine studies. 13 Do you see that? 14 MR. FREEMAN: Are you all on a 15 different page? 16 A. I'm sorry -- oh, yes. 17 Q. If you look in the left-hand 18 corner it says PZ 1124,895. 19 A. Uh-huh. 20 MR. FREEMAN: Are you on the same 21 page? 22 THE WITNESS: We are now, I think. 23 (DISCUSSION OFF THE RECORD.) 24 Q. Special fluoxetine studies, do Page 100 1 you see that? 2 A. Uh-huh. 3 Q. And at the top it says MDD no 4 code break? 5 A. Yes. 6 Q. Do you recall that study? 7 A. No. 8 Q. Go to the last -- the third 9 from the last page. On my copy it's nine one one 10 in the lower right-hand corner. 11 A. I'm sorry, it's nine one -- 12 Q. One one. It should be the 13 next one. 14 A. Okay. 15 Q. It says weekly dosing? 16 A. Yes. 17 Q. It appears from this that the 18 weekly dosing study was done at this point, does 19 it not? 20 A. I can't really tell. I 21 believe that this would have been a copy of a 22 slide that was used for discussion with, one 23 would hope, the speaker shedding a little further 24 light. Page 101 1 Q. Okay. Look at the last page 2 of the exhibit. It says other trials, and it 3 talks about suicide slash parasuicide? 4 A. Yes. 5 Q. Do you recall studies 6 regarding either one of those issues? 7 A. First, I don't recall any such 8 studies, and second, I have no idea what the term 9 parasuicide means. 10 Q. That was my next question, I 11 was going to ask you if you knew what that meant. 12 Let's go back to Exhibit Number 2. 13 A. Yes. 14 Q. How is it determined which 15 adverse events to list in the initial package 16 insert, is there a criteria that was used? 17 A. I really don't remember. 18 Q. Do you know if any adverse 19 events were purposely excluded for some reason or 20 another? 21 A. Not to my knowledge. 22 Q. The adverse events that were 23 listed in the initial package insert, were those 24 adverse events only those events that a causal Page 102 1 relationship to the use of fluoxetine could be 2 established or was it all adverse events that 3 occurred during the clinical trials? 4 MR. FREEMAN: Read the question back. 5 (THE COURT REPORTER READ BACK THE 6 REQUESTED TESTIMONY.) 7 A. It was not -- the list is not 8 only those where a causal relationship could be 9 established. By and large, one can't establish a 10 causal relationship, and in any event, they list, 11 for example, on the right side of page nine, 12 would not consist of adverse events with an 13 established causal relationship to placebo. 14 These would have been events reported regardless 15 of what one might conjecture about causal 16 relationship. 17 Q. Here it says that information 18 presented in the table which follows is derived 19 from double-blind placebo controlled studies of 20 five or six weeks duration. Do you see that? 21 A. Not offhand. Which page, 22 please? 23 Q. Same page, at the top, second 24 sentence. Page 103 1 A. Oh, yes. 2 Q. Is it your understanding from 3 this document that this list at least was only 4 those -- was taken only from those studies where 5 fluoxetine was only compared to placebo and not 6 another active comparitor? 7 MR. FREEMAN: If you know. 8 Q. If you know. 9 A. I really don't remember. 10 Q. Well, certainly at this time 11 there were clinical trials at least being 12 conducted comparing fluoxetine, placebo and 13 imipramine, were there not? 14 A. Being conducted and/or 15 completed. 16 Q. Do you recall why the adverse 17 events occurring in those clinical trials are not 18 included in those lists? 19 MR. FREEMAN: You're assuming they 20 were not, she hadn't stated one way or another. 21 A. I believe that the fluoxetine 22 group and the placebo group, as depicted here, 23 probably included those trials. 24 Q. Okay. But the adverse events -- Page 104 1 A. Where there was a third group 2 of patients. 3 Q. Okay. But there's no list 4 here for imipramine, for instance? 5 A. Correct. 6 Q. So to make sure I understand, 7 it's your recollection that the adverse events 8 included in this list were adverse events 9 occurring during clinical trials that had been 10 run or were being run to date regardless of 11 whether or not there was an active comparitor 12 arm? 13 A. That's my best recollection. 14 Q. A couple of seconds ago you 15 said that by and large you can't establish a 16 causal relationship. Why do you say that? 17 A. To me that seems perfectly 18 obvious, and yet I'm finding it difficult to 19 articulate exactly why. Perhaps the very fact 20 that one has the list of fluoxetine and the list 21 of placebo looks very similar is illustrative of 22 my point. As an example, six percent of the 23 patients receiving fluoxetine had musculoskeletal 24 aches and pains. If I were the physician Page 105 1 treating one of those patients, even if I knew 2 the test drug, which wasn't the case here, I 3 wouldn't be able to know with any degree of 4 certainty whether fluoxetine had caused it or 5 not. And when you -- in this case there's a very 6 comparable incidence of the same symptoms 7 associated with placebo administration, and one 8 would conclude that probably musculoskeletal 9 aches and pains do not result from fluoxetine. 10 Q. Well, how about nausea, where 11 twenty-three percent of the patients on 12 fluoxetine experienced nausea and ten percent of 13 the patients on placebo experienced nausea, what 14 would be the situation with regards to 15 establishing a causal relationship in that 16 instance? 17 A. Okay. I would conclude from 18 that that fluoxetine probably results in nausea 19 in some patients, but with individual patients, 20 that's a different situation. 21 Q. Well, if you wanted to see if 22 an individual patient was having that reaction to 23 the drug, what could you do to determine that? 24 A. You could take the patient off Page 106 1 the drug. However, if the benefit were 2 considerable and the nausea was mild, not of a 3 clinical protocol but a clinical practice and if 4 the patient were willing to put up with the 5 nausea, I would probably think to myself, yes, 6 the drug might be causing this, I'm not seeing 7 anything else that troubles me in the way of 8 gastrointestinal symptoms. If the patient were 9 willing, I would continue the drug. 10 Q. Let's limit it to deciding 11 whether or not the adverse event is related to 12 the drug, okay, as opposed to the other practical 13 implications of treating the individual patient. 14 A. Okay. 15 Q. You said one of the ways that 16 you can try to determine a causal relationship is 17 to take the patient off the drug and see if the 18 adverse event subsides, correct? 19 A. Yes. Sometimes followed by 20 readministration of the drug. 21 Q. Commonly known as 22 rechallenging? 23 A. Yes. 24 Q. Were you aware at the time -- Page 107 1 during the time you worked at Lilly of any 2 patient that suffered any adverse event that was 3 rechallenged on fluoxetine to see if it was 4 related to that adverse event? 5 A. I don't recall any such event. 6 It may have happened. 7 Q. Would you agree with me that 8 rechallenging a patient is probably, with regards 9 at least to that individual patient, the best way 10 to try to determine whether or not there's a 11 causal relationship between an adverse event and 12 the use of a particular drug? 13 A. If one's goal is to try to 14 decide the question of causality, it's probably 15 best. But again, as a clinician, I'm going to 16 consider other factors. 17 Q. Okay. But I'm not talking 18 about as a clinician, I'm talking about -- put 19 yourself back when you worked for Lilly, okay. 20 If you wanted to get a true understanding of 21 whether or not, at least in the individual client 22 or individual patient, whether or not an adverse 23 event was caused by the drug, would you agree 24 with me that the best way to do that would be to Page 108 1 rechallenge that patient? 2 MR. FREEMAN: Are we talking about 3 nausea? 4 MS. ZETTLER: Any event. 5 MR. FREEMAN: Suicidal ideation 6 included? 7 MS. ZETTLER: Yes. 8 MR. FREEMAN: See where she's going? 9 THE WITNESS: That's why I'm 10 hesitating. It's an individual case-by-case 11 situation, and I just don't know how to answer 12 that. 13 MS. ZETTLER: Motion to strike the 14 answer as nonresponsive, and I object to Joe's 15 continued coaching of the witness with his 16 comments or questions. 17 MR. SMITH: Me, too. 18 MS. ZETTLER: Thanks, Paul. 19 Q. Doctor, let's take suicidal 20 ideation. Say you have a patient who is placed 21 on fluoxetine who is not suicidal and they become 22 suicidal, is it not true that the best way to see 23 if that person became suicidal because of the 24 drug would be to take them off the drug and then Page 109 1 rechallenge them with it later on? 2 MR. FREEMAN: Would you add and 3 hospitalize him? 4 MS. ZETTLER: No. 5 MR. FREEMAN: You're going to leave 6 him out? 7 MS. ZETTLER: No, I didn't say that 8 either. You're reading something into my 9 question, and again you're trying to coach the 10 witness. 11 MR. FREEMAN: You have to be specific, 12 you cannot ask general questions. 13 MS. ZETTLER: I'm talking about just 14 whether or not there is a causal relationship, 15 not whether or not it's ethical, in your opinion, 16 not whether or not it's the best thing for the 17 patient. I'm talking strictly about whether or 18 not the person's reaction -- the person's 19 condition is a reaction to Prozac or a condition 20 or reaction to some other thing or underlying 21 part of the disease. 22 A. Now could you repeat the 23 question, please? 24 Q. Let me ask it this way: If Page 110 1 you have a patient who is placed on fluoxetine, 2 that person after being placed on fluoxetine 3 becomes suicidal and that person is then taken 4 off of the fluoxetine and the suicidality goes 5 away, okay, do you follow me so far? That person 6 is then placed back on the fluoxetine and once 7 again becomes suicidal after being placed back on 8 the fluoxetine, would it be fair to say that 9 there is a reasonable causal relationslip between 10 the fluoxetine and that person's suicidality? 11 A. It's possible, but far from 12 certain. 13 Q. Is it probable? 14 A. I think possible is as far as 15 I'm prepared to go. 16 Q. What other factors would you 17 need to take into consideration to become more 18 certain that the suicidality is a reaction to the 19 drug? 20 A. Well, first I have difficulty 21 with your word suicidality, it's not a word that 22 I hear clinically. 23 Q. Suicidal ideation, suicidal 24 gestures, suicide attempts, successful suicide, Page 111 1 how's that? 2 A. Rather different situations. 3 MR. FREEMAN: Successful suicide, you 4 can't put the patient back on the drug so let's 5 take that out. 6 MS. ZETTLER: Defining suicidality -- 7 MR. SMITH: Boy, you should have been 8 a scientist, Joe. 9 (DISCUSSION OFF THE RECORD.) 10 A. Suicide ideation can fluctuate 11 fairly rapidly. A patient may be more 12 forthcoming in one interview than another. 13 Judgment in this area is very difficult to 14 psychiatrists in general, and I'm certainly not 15 totally successful in predicting the actual risk. 16 My concern, as a clinician, and I'm sorry, my 17 concern there, even though I could not actually 18 view the patients, is primarily the patient's 19 welfare. Trying to determine in an individual 20 case the cause or to eliminate a cause would not 21 be my primary concern. 22 Q. What about the welfare of the 23 patient population in general that's being 24 prescribed Prozac, are you concerned about their Page 112 1 welfare, Doctor? 2 A. Yes. 3 Q. Who are you more concerned 4 with, the individual patient who may be 5 rechallenged under clinical conditions with a 6 drug that may cause them to become suicidal or 7 are you more concerned with the population at 8 large that are going to be taking the drug not 9 knowing what the side effect profile is? 10 A. It seems, Ms. Zettler, and 11 forgive me if you regard my answer as 12 nonresponsive, but despite the best efforts at 13 establishing with any degree of certainty whether 14 an individual patient, some exacerbation, say, of 15 suicidal ideation or a suicidal gesture was 16 attributable to fluoxetine, contributes 17 absolutely nothing to one's knowledge about the 18 next individual patient. The clinician deals 19 with one individual at a time and I could see no 20 purpose to engaging in what might be a dangerous 21 exercise simply to add a little information about 22 an individual patient which cannot then be 23 generalized. 24 Q. As a clinician, would you Page 113 1 prefer to go into prescribing the medication with 2 all possible information that is relevant to your 3 use of that drug or would you rather go in 4 blindly not knowing what the true profile of the 5 drug is? 6 A. Neither. I don't think I'm 7 blind with respect to any drug that I would 8 prescribe. I also recognize that the reality is 9 that one cannot establish causal relationships in 10 many situations, even if ethics are not a major 11 consideration. 12 Q. So you're saying that there is 13 no way you can establish a causal relationship 14 between the use of fluoxetine and any adverse 15 event whatsoever? 16 A. I don't think that's quite 17 what I have said. 18 Q. Well, then, clarify it for me, 19 Doctor, because I don't understand the 20 differentiation. 21 A. Well, I'm sorry, I've made 22 what I regard as a reasonable effort, and I 23 really can't think of any other way of expressing 24 what I have been trying to say. Page 114 1 Q. On the one hand you say it's 2 not possible to establish a causal relationship, 3 and on the other hand you say that it is. So I 4 guess I'm confused as to what you mean by it's 5 not possible to establish a causal relationship. 6 A. It seems to me I'm being a bit 7 misquoted. 8 Q. Straighten me out then. 9 A. I thought that was what we had 10 a court reporter here for. 11 Q. I'm asking some questions now, 12 Doctor, and I would like your help at least to 13 get me through this one part. 14 A. I have attempted to be 15 helpful, I have obviously not been as successful 16 as you would desire. I really can't think of any 17 other ways of saying what I have been attempting 18 to say. 19 Q. Is it your testimony that it's 20 possible to establish a causal relationship 21 between the use of fluoxetine and a side effect 22 such as nausea, and not possible to establish a 23 causal relationship between the use of fluoxetine 24 and suicidal ideation? Page 115 1 A. I need to ask you to clarify 2 whether you're referring to groups of patients or 3 to an individual patient, because I think that is 4 part of my answer. 5 Q. Okay. Let's start with 6 individual patients. 7 A. May I start with an individual 8 patient with nausea? 9 Q. Sure. 10 A. The patient has experienced 11 nausea, the patient is receiving -- has been 12 receiving fluoxetine, and for reasons that I 13 cannot really imagine, I'm extremely concerned 14 with whether nausea was caused in that particular 15 patient by fluoxetine. And in a way that seems 16 to me utterly pointless, I could stop the 17 fluoxetine, see if the nausea disappears after 18 some appropriate period, and I don't quite know 19 offhand what that would be, I could reinstitute 20 the fluoxetine and see if the nausea recurred, 21 and if it did, I could then stop the fluoxetine, 22 see if the nausea disappeared, and I suppose I 23 could in theory do that another couple of times, 24 each time increasing the certainty that nausea Page 116 1 was indeed caused by fluoxetine in that 2 individual patient. I recognize that nausea 3 might be caused by fluoxetine, and I find 4 pursuing that in an individual patient, even with 5 what I'm assuming to be a fairly mild situation, 6 a totally pointless exercise. 7 Q. What about groups? 8 A. Group data such as you cited 9 from page whatever it was -- oh, page nine. 10 Group data tell me simply that nausea occurred 11 with a higher incidence in fluoxetine treated 12 patients than it did with placebo treated 13 patients, from which I conclude that in some 14 patients anyway fluoxetine probably causes 15 nausea. 16 Q. Okay. How does that differ in 17 groups with suicidal ideation? 18 MR. SMITH: What did you say? 19 Q. I said how does that differ in 20 groups with suicidal ideation? 21 A. Offhand, I'm not sure that it 22 does except of course that that is a clinical and 23 much more serious idea. Also, suicidal ideation 24 in a population of depressed patients is going to Page 117 1 fluctuate, be present at one interview, not 2 present or denied in another. 3 Q. That should be true across all 4 treatment categories, though, should it not? 5 A. Probably. 6 Q. So if you had listed on here 7 suicidal ideation or suicide attempt, fourteen or 8 sixteen on fluoxetine and six or seven on 9 placebo, could you then make the same judgment 10 that you made with regards to the nausea, that in 11 some patients it may produce suicidal ideation? 12 A. Perhaps. 13 Q. What was the special NDA 14 submission that you made with regards to 15 fluoxetine prior to the actual NDA being 16 submitted in 1983? 17 A. I have no earthly idea, but 18 will shortly. 19 Q. I hope so. 20 (DISCUSSION OFF THE RECORD.) 21 (PLAINTIFFS' EXHIBIT NO. 6 WAS 22 MARKED FOR IDENTIFICATION AND 23 RECEIVED IN EVIDENCE.) 24 A. I note with dismay that the Page 118 1 term New Drug Application was not capitalized, 2 and I cannot imagine why, but I have indeed read 3 the cover letter. 4 Q. Does this refresh your 5 recollection as to what the special submission 6 is? 7 A. Not beyond what the cover 8 letter says, no. I believe the reason for the 9 submission was to elicit comments from FDA really 10 on the format, the presentation of a study 11 summary, perhaps on data analysis. 12 Q. Weren't you familiar with all 13 of that from working at the FDA, the format, et 14 cetera, when you worked after all in the division 15 that was going to be reviewing this special 16 submission, correct? 17 A. That's true, however something 18 over a decade had elapsed, point one, and point 19 two, FDA preferences for format and data analysis 20 were often the -- at the preference of the 21 individual reviewer, tended to change with fully 22 as much scientific merit as the case with women's 23 skirt lengths. 24 Q. Which have actually been Page 119 1 fairly consistent in the past few years, haven't 2 they? Upper right-hand corner there's a number 3 written, can you tell me what that means? Not 4 the E-5, but the other one, looks like three 5 three seven one point one. 6 A. That may have been page number -- 7 pagination in those days I think for IND 8 submissions was just sequential. I wouldn't have 9 remembered that but for the notation here in the 10 second paragraph. 11 Q. Would this have been, the 12 three three seven one point one, would that be 13 the three thousand three hundred and 14 seventy-first point one document or page? 15 A. Page, I think, but why the 16 decimal, I have no idea. 17 Q. And according to this letter, 18 the special submission was started with the page 19 number one, correct? 20 A. Yes. 21 Q. Was the special submission 22 filed with the IND on the drug, if you know? 23 A. Since the IND number is 24 referenced, I assume so. Page 120 1 Q. If I wanted to find this 2 special submission at the FDA, I should go look 3 in the IND file? 4 A. I would have said yes but for 5 your question which suggested that you might not 6 find it after all. 7 Q. Well, I mean, don't read 8 anything into my question. To the best of your 9 recollection, if I wanted to find this submission 10 would I look in the IND file at the FDA? 11 A. Yes, although obviously this 12 was a bit unusual, and may I clarify a little 13 bit? 14 Q. Uh-huh. 15 A. From time to time submissions 16 were made almost to individuals rather than the 17 agency in an effort to facilitate discussion. 18 There was nothing inappropriate or underhanded 19 about that practice, it was a way of trying to 20 facilitate dialogue, if you will. 21 Q. Would you then -- were those 22 desk copies? 23 A. Sometimes, uh-huh. 24 Q. Would those desk copies also Page 121 1 be filed with the appropriate IND or NDA file? 2 A. Usually. 3 Q. Can you recall any instance 4 with regards to fluoxetine where that was not the 5 case while you were there? 6 A. I don't recall. 7 Q. This being addressed to the 8 FDA, Bureau of Drugs, Attention: Document 9 Control Room, would that indicate that this 10 submission was actually filed to the IND as 11 opposed to being sent to the FDA as a desk copy 12 or an individual copy like you were talking about 13 earlier? 14 A. It appears that way. 15 Q. In your experience at the FDA, 16 had you known any other situation where a drug 17 company submitted a pre or mini NDA prior to 18 submitting the actual NDA on a drug? 19 A. Yes, that happened from time 20 to time. 21 Q. What situations would that 22 happen in? 23 A. I can't delineate at this late 24 date. Page 122 1 Q. To your knowledge, prior to or 2 while you were at Lilly, had Lilly ever applied 3 for registration of a psychotropic drug with the 4 FDA for marketing here in the United States? 5 A. Lilly marketed Aventyl. 6 Q. Do you know when that NDA was 7 submitted? 8 A. Well before I was working at 9 FDA. 10 Q. How about between the period 11 of time that you left the FDA and started working 12 at Lilly? 13 A. Oh, is your question did they 14 market or submit another one? 15 Q. Right. 16 A. Not that I know of, not that I 17 can remember now. 18 Q. Was Pergolide a psychotropic 19 medication? 20 A. No. 21 Q. What kind of medication is 22 that? 23 A. It's used for Parkinson's 24 disease. I'm sorry, I'm on the edge of what Page 123 1 might or might not be confidential. 2 Q. Okay. 3 A. It was studied for Parkinson's 4 disease. 5 MR. SMITH: Is it a CNS drug? 6 THE WITNESS: Yes. 7 Q. Would it have been with the 8 application or the NDA have been submitted to the 9 same division that Prozac was? 10 A. Yes. 11 Q. Was that NDA submitted before 12 or after Prozac's NDA? 13 A. After. 14 Q. Any other CNS drugs that Lilly 15 was seeking approval on from the FDA where the 16 NDA was submitted prior to fluoxetine? 17 A. Nabilone was submitted, I 18 believe, prior to -- I'm almost sure it was prior 19 to fluoxetine. 20 Q. Do you recall how long prior 21 to fluoxetine? 22 A. Not clearly. It seems to me 23 that Nabilone was probably the first NDA that I 24 submitted on behalf of Lilly after I was there. Page 124 1 Much of the work having been done before I got 2 there. 3 Q. Was there a mini NDA or 4 special submission made on Nabilone as was made 5 on fluoxetine? 6 A. I don't remember one. 7 (PLAINTIFFS' EXHIBIT NO. 7 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Have you had a chance to 11 review Exhibit 7? 12 A. Yes. 13 Q. Okay. Exhibit 7 purports to 14 be a cover memo written by you to Doctor 15 Lemberger and Doctor Stark as primary recipients, 16 and four other Lilly employees as CCs, correct? 17 A. Yes. 18 Q. And the purpose of the memo is 19 to transmit a copy of a letter dated May 17, 1982 20 to you from Doctor Paul Leber, Acting Director, 21 Division of Neuropharmacological Drug Products, 22 correct? 23 A. Yes. 24 Q. At the FDA, right? Page 125 1 A. Yes. 2 Q. In that letter, Doctor Leber 3 talks about requests that you apparently made to 4 amend protocols twenty-six, twenty-eight and 5 thirty-six, correct? 6 A. Yes. 7 Q. And it says -- he said that he 8 has no objection to a couple of the requests or a 9 couple of the amendments that you proposed, but 10 recommends that the patients remain blinded if 11 you're going to switch them or continue them on 12 in trials after the double-blind phase, correct? 13 A. You said patients remain 14 blinded. 15 Q. Right. It says we also 16 recommend when patients complete the blind phase 17 of the trial, you maintain the blind and either 18 routinely switch the patients to fluoxetine if 19 they were appropriate candidates for the 20 long-term exposure or continue patients on the 21 blind medication for the extended phase, correct? 22 A. Yes. 23 Q. His basic objection was 24 breaking the blind when patients had finished the Page 126 1 blind phase of the trial? 2 A. Yes. 3 Q. And the reason he objected to 4 that is because he felt that breaking the blind 5 would educate the investigators to the action and 6 adverse event profile of the drug and possibly 7 make it possible for them to determine what drug 8 other patients were on that were still blinded, 9 correct? 10 A. Yes. 11 Q. Now, when you have a clinical 12 trial, you're running a clinical trial on a drug, 13 you don't have, say, forty patients necessarily 14 all on the trial together starting and completing 15 at the same time, correct? 16 A. Obviously not, correct. 17 Q. So you would have -- say if 18 you have a clinical trial where you want to have 19 seventy-five patients complete the trial, you 20 could have ten patients start one week and 21 another, like, six weeks later have another ten 22 patients start, correct? 23 A. It's more likely that one 24 would start some patients this week and Page 127 1 additional patients the following week. 2 Q. You wouldn't be running all 3 seventy-five patients at once, correct? 4 A. Correct. 5 Q. It's theoretical that you 6 could have some patients complete the study 7 before other patients begin in the study, 8 correct? 9 A. Absolutely. 10 Q. And Doctor Leber was concerned 11 that if you were unblinding patients that 12 participated, say, in the first week of the study 13 at the end of their period to be on the study 14 and, say, started other patients on the study, 15 the investigator would be educated as to what 16 drug the person may or may not be on because of 17 their experience with the other patients, 18 correct? 19 A. That was the concern that was 20 expressed, yes. 21 Q. In fact this became a fairly 22 serious issue between Lilly and the FDA, did it 23 not? 24 A. I really don't remember. Once Page 128 1 I read this letter and others that we've 2 discussed, it seems a bit familiar, but to go 3 beyond the letter, I can't remember what 4 happened. I may well have drafted a response, I 5 guess my cover memo suggests that I did. 6 (PLAINTIFFS' EXHIBIT NO. 8 WAS 7 MARKED FOR IDENTIFICATION AND 8 RECEIVED IN EVIDENCE.) 9 Q. Have you had a chance to 10 review Exhibit 8? 11 A. Yes. 12 Q. Do you recall this exhibit, 13 Doctor Dobbs? 14 A. At the risk of repeating 15 myself endlessly, it's the same situation, I've 16 looked at it, it seems somewhat familiar. 17 Q. Okay. 18 A. It also bears a striking 19 resemblance to my writing style. 20 Q. So you're saying that you 21 believe you did draft this? 22 A. I think I drafted this, yes. 23 Q. It's a two page response, it 24 appears, to the Food and Drug Administration to Page 129 1 Doctor Leber's letter dated May 17, 1982 that we 2 were just talking about, correct? 3 A. Yes. 4 Q. And in the letter you suggest 5 Lilly's position that breaking the blind at the 6 end of the study does not educate the 7 investigator or possibly educate the investigator 8 as to the profile of the drug for future 9 patients, correct? 10 A. Yes. I can't today express it 11 any better than I did then. 12 Q. Do you agree with that 13 proposition, Doctor, that breaking the blind on 14 earlier patients does not educate the 15 investigator as to the profile of the drug, 16 either side effect or otherwise? 17 A. I assume we're talking about 18 fluoxetine and the specifics studies. 19 Q. Sure. 20 A. I can't, off the top of my 21 head, generalize. I think my point here was that 22 there was nothing so unique about the side 23 effects, much less the efficacy of fluoxetine, 24 that the investigator would thereby figure out Page 130 1 what the next patient and the next patient were 2 likely to be taking. 3 Q. Well, is it one of the claims 4 about fluoxetine that it lacks a number of 5 anticholinergic effects that tricyclic 6 antidepressants have, such as dry mouth, nausea, 7 et cetera? 8 A. May I refer back to that draft 9 insert? 10 Q. Sure. It's Exhibit 2, I 11 believe. 12 A. Yes, on page nine. I 13 couldn't, of course, recall the figures. And if 14 I may conjecture, if we had an amitriptyline 15 group in here at a goodly dosage, the incidence 16 there would be, depending on dosage, twenty, 17 thirty, percent higher, I don't know. My point 18 is that if one is thinking of an individual 19 patient's dry mouth can occur in association with 20 fluoxetine, can occur with amitriptyline, can 21 occur with several others, and can occur with 22 placebo, and so if the investigator sees a 23 patient who says -- I'm to use a frequent 24 expression -- I'm spitting cotton, and if I were Page 131 1 the investigator, I wouldn't be able to figure 2 out, therefore, that the patient was on 3 amitriptyline or fluoxetine or placebo because 4 dry mouth can occur. 5 Q. But if you saw enough patients 6 who were suffering dry mouth and you knew from 7 your previous experience that imipramine, for 8 instance, causes dry mouth in patients, you would 9 fairly quickly be able to educate yourself that 10 those people on the clinical trial who were 11 suffering from dry mouth would more likely be on 12 imipramine than placebo, would you not? 13 A. A little more likely, yes, but 14 that's just a probability. I still wouldn't know 15 whether that was imipramine or what. 16 Q. In fact a lot of these guys 17 who have been in the business for years and years 18 and years are pretty good at being able to pick 19 out what drug a patient is on at any given time, 20 are they not, Doctor? Not just fluoxetine, I'm 21 talking about anything. 22 A. I have heard investigators 23 claim they can, and on one or two occasions, I 24 don't know how good they actually are. Page 132 1 Q. They at least think they can, 2 don't they? 3 A. I have met one or two that 4 thought they could. 5 MS. ZETTLER: Let's take a break. 6 (A SHORT RECESS WAS TAKEN.) 7 * * * * * * * * * * 8 EXAMINATION 9 BY MR. SMITH: 10 Q. Doctor Dobbs, my name is Paul 11 Smith, we met. 12 A. Yes. 13 Q. I represent a number of 14 individuals whose lives have been adversely 15 affected by Prozac, or their family member's 16 consumption of Prozac. I have filed lawsuits on 17 their behalf in various courts, and your 18 deposition here today will be used in evidence in 19 some or all of those trials, do you understand 20 that? 21 A. I understand that. I'm 22 troubled by what I perceive to be a conclusion 23 that I do not necessarily share. 24 Q. Oh, I'm not going to ask you Page 133 1 to agree that their problems were a result of 2 Prozac, I just wanted to explain to you who I am 3 and what my function is here, all right? 4 A. Understood. 5 Q. You obviously have had an 6 opportunity to speak with attorneys for Eli Lilly 7 and Company on a number of occasions concerning 8 your work at Lilly and your testimony here today, 9 have you not? 10 A. On several occasions. 11 Q. But you and I have not 12 discussed the substance of your testimony at all, 13 have we? 14 A. That's correct. 15 Q. Nor has anybody from my office 16 discussed the substance of your testimony with 17 you, have they? 18 A. That's correct. 19 Q. And Ms. Zettler, even though 20 she's had some communications with you concerning 21 your availability to give your deposition, has 22 not discussed with you the substance of your 23 testimony, has she? 24 A. That's correct. Page 134 1 Q. But the lawyers from Eli Lilly 2 and Company have, haven't they? 3 A. Yes. 4 Q. They've asked you your 5 opinions concerning some of the matters in issue, 6 have they not? 7 A. Yes. 8 Q. And discussed with you to some 9 extent what their perception of the evidence has 10 been in this case? 11 A. Yes. 12 Q. You understand that we've 13 probably taken forty or fifty depositions in this 14 lawsuit, do you understand that? 15 A. Yes. 16 Q. And we have taken some 17 depositions where some individuals were quite 18 knowledgable and others had quite a limited 19 knowledge concerning matters that we were asking 20 them about. You, however, to me, strike me as 21 one who may have knowledge concerning a number of 22 issues. Do you understand that? 23 A. Yes. 24 Q. The reason that -- and it just Page 135 1 struck me during the course of your deposition 2 that you may have a broader range of knowledge 3 than some of the witnesses we talked to because, 4 number one, you're a medical doctor. Some of 5 these witnesses we've discussed Prozac with are 6 not medical doctors, correct? 7 A. I certainly take your word for 8 that. Obviously, I don't know whom you deposed. 9 Q. For instance, Doctor Paul 10 Stark, one of the medical monitors with Eli Lilly 11 and Company during the time that you were 12 president of Eli Lilly and Company, he's not a 13 medical doctor? 14 A. That's correct. 15 Q. And in fact he's had no 16 training in psychiatry or psychology, did you 17 know that? 18 A. I know that he hasn't in 19 psychiatry, I don't know whether Paul had any 20 courses in psychology as an undergraduate or not. 21 Q. He swore under oath that he 22 hadn't. 23 A. I accept your word for that. 24 Q. Additionally, some of the Page 136 1 witnesses that we've deposed have been medical 2 doctors but have not been psychiatrists. 3 A. Again, I accept your word for 4 that. 5 Q. And obviously you are a 6 psychiatrist. 7 A. Yes. 8 Q. And Prozac, fluoxetine 9 hydrochloride is a medication given to people 10 with psychiatric illnesses, correct? 11 A. Yes. 12 Q. So, therefore, we're going to 13 have the benefit of your testimony as not only a 14 medical doctor, but a psychiatrist, one who has a 15 specialty of treating individuals with mental 16 illnesses, correct? 17 A. Correct. 18 Q. Do you agree, Doctor Dobbs, 19 that depression is a mental illness? 20 A. Yes. 21 Q. Do you agree, Doctor Dobbs, 22 that for some individuals suffering from some 23 types of depression, that there is scientific 24 evidence that that depression is a result of Page 137 1 physiological factors? 2 A. I accept that for many 3 patients there are physiological, or to be a bit 4 technical, pathophysiological changes which 5 underlie the depression. The extent to which 6 such beliefs is based on animal data and theory, 7 I can't really elucidate right now. 8 Q. Do you have an opinion, Doctor 9 Dobbs, as a psychiatrist and medical doctor and 10 one knowledgable concerning antidepressants and 11 concerning depression, whether or not depression 12 and the serotonin system are related to some 13 extent in some individuals? 14 A. I share that opinion, yes. 15 Q. That it's related -- 16 A. Yes. 17 Q. -- to some extent in some 18 individuals? 19 A. Yes. 20 Q. Would you qualify that as I 21 have qualified that, that is depression in some 22 individuals in some instances is a result of some 23 type of imbalance or, I want to say, abnormality -- 24 not necessarily abnormality, but some deficiency Page 138 1 or some problem in the serotonin system in that 2 individual? 3 A. I couldn't have said it better 4 myself, Mr. Smith. 5 Q. The people that we've talked 6 to also who have given their sworn testimony in 7 this case, also some of the medical doctors, 8 psychiatrists, who worked for Lilly never 9 practiced psychiatry, do you understand that? 10 A. Yes. 11 Q. But you are an individual who 12 has been employed by Lilly? 13 A. Yes. 14 Q. Who has worked for the 15 pharmaceutical company in connection with 16 psychiatric drugs who has practiced psychiatry, 17 correct? 18 A. Yes. 19 Q. Both before you joined Lilly? 20 A. Yes. 21 Q. And now, after you've left 22 Lilly? 23 A. Yes. 24 Q. Additionally, you're, I Page 139 1 believe, the first witness who is a medical 2 doctor, psychiatrist, that's also worked for more 3 than one pharmaceutical company who has now gone 4 back into private practice. 5 A. My career has taken some 6 unusual twists and turns. 7 Q. And finally, you also are an 8 individual, one of the first that we've talked 9 with that's ever worked as a medical doctor, 10 psychiatrist, for the Food and Drug 11 Administration, correct? 12 A. Yes. 13 Q. And when you were in the Food 14 and Drug Administration, as I understand it you 15 were with that division or department that was 16 responsible for psychotropic drugs such as 17 Prozac? 18 A. Yes. 19 Q. Obviously when you were with 20 the Food and Drug Administration, there hadn't 21 been any application made or there was no work 22 being done on Prozac as far as you know? 23 A. That's correct. 24 Q. And you don't know of anything Page 140 1 that's come to light since that makes you believe 2 that Prozac was a substance actively being 3 investigated by Lilly back when you were with the 4 FDA? 5 A. It's my understanding that the 6 work on fluoxetine and preclinical studies 7 started well after I left FDA. 8 Q. You left the FDA in -- 9 A. End of 1970. 10 Q. All right. Does the FDA have 11 or did this FDA division that you were with, what 12 was that, neuropsychopharmacological drugs? 13 A. It wasn't quite that bad. It 14 had various terms while I was there, but it was -- 15 at the time I left, anyway, it was the division 16 of neuropharmacological drug products, the same 17 division that was noted on Doctor Leber's letter, 18 which is Exhibit 7. 19 Q. All right. 20 A. No -- yes, sorry. 21 Q. And the FDA, and specifically 22 that division, didn't have a laboratory where 23 they did clinical studies on psychotropic drugs, 24 did they? Page 141 1 A. That's correct. 2 Q. We people -- we lay people 3 think that when a drug is FDA approved, that the 4 FDA actually takes that medication, runs chemical 5 tests and clinical trials on it, correct, or 6 that's what a lot of us think? 7 A. I imagine that that could be 8 true. I have done no survey of laymen's opinions 9 of drug approval process. 10 Q. But that is not true, is it, 11 Doctor Dobbs, that the Food and Drug 12 Administration tests psychotropic medications and 13 conducts clinical trials on any particular 14 psychotropic drug such as Prozac? 15 A. FDA rarely contracts clinical 16 trials, in special circumstances they do not 17 routinely conduct clinical trials. They do, 18 however, do some chemical testing. 19 Q. All right. Now, to be clear, 20 the United States Food and Drug Administration 21 did not do any clinical trials with respect to 22 Prozac as far as you know, did they? 23 A. That's correct, they did not. 24 Q. You submitted to the United Page 142 1 States Food and Drug Administration a New Drug 2 Application under your signature, did you not? 3 A. Correct. 4 Q. And part of that application 5 stated that Lilly would perform clinical trials, 6 did they not? 7 A. Would perform and had 8 performed, yes. 9 Q. Had and would? 10 A. Yes. 11 Q. And it didn't ask the Food and 12 Drug Administration to do any independent 13 clinical trials, did they? 14 A. That's correct. 15 Q. And you don't know of any 16 independent clinical trials that the United 17 States Food and Drug Administration did in 18 connection with Prozac, do you? 19 A. No, I do not. 20 Q. And, therefore, all clinical 21 data that was submitted to the United States Food 22 and Drug Administration was clinical data 23 submitted by Eli Lilly and Company, was it not, 24 prior to its being approved? Page 143 1 A. Up to the point where I left 2 Lilly, that's true. 3 Q. And you left Lilly in mid-'85? 4 A. Correct. 5 Q. And it would not surprise you 6 to know that there was no other independent data 7 submitted to the United States Food and Drug 8 Administration concerning any independent 9 clinical trials contracted out by the United 10 States Food and Drug Administration or any other 11 regulatory body, would there? 12 A. It would not surprise me to 13 learn that there were no such studies. 14 Q. That's not unusual, is it? 15 A. That's correct. 16 Q. That the sponsor, the 17 pharmaceutical manufacturer, does the clinical 18 trials, correct? 19 A. Well, as a question, though, 20 the sponsor and its representatives -- the 21 sponsor is called the sponsor because they 22 sponsor clinical trials actually conducted by 23 investigators, except for the Phase 1 trials. 24 Q. And the investigators that do Page 144 1 the human clinical trials other than the Phase 1 2 trials are investigators that are hired by the 3 sponsors, are they not? 4 A. That's true. 5 Q. In other words they're paid -- 6 those investigators that did clinical trials on 7 Prozac to be submitted to the FDA were paid by 8 Eli Lilly and Company as far as you know, were 9 they not? 10 A. Yes. 11 Q. And did you know that their 12 clinical trial investigations was submitted by 13 the investigators to Lilly? 14 A. I beg your pardon? 15 Q. Well, while you were at Lilly -- 16 A. Yes. 17 Q. -- the work that the 18 investigators did -- 19 A. Yes. 20 Q. -- was submitted to Lilly. 21 A. Yes. 22 Q. Correct? 23 A. Yes. 24 Q. And then Lilly submitted that Page 145 1 data to the Food and Drug Administration, 2 correct? 3 A. After compilation and analysis 4 and a narrative summary report and so forth, yes. 5 Q. In other words, the 6 information that the investigators who were paid 7 by Lilly were collecting, were doing, that work 8 they were doing was not sent directly to the Food 9 and Drug Administration, was it? 10 A. That's correct. 11 Q. It was sent to Eli Lilly and 12 Company, wasn't it? 13 A. Yes. 14 Q. Then Eli Lilly and Company 15 did, as you say, an analysis, compilation and 16 data entry or whatever is necessary and then 17 submitted that data to the Food and Drug 18 Administration, correct? 19 A. That's correct. 20 Q. And not necessarily was that 21 data submitted in the same form to the Food and 22 Drug Administration as it was submitted to Lilly, 23 correct? 24 MR. FREEMAN: Be more specific about Page 146 1 your question. 2 MR. SMITH: In what respect? 3 MR. FREEMAN: The underlying data, I 4 mean I don't want the record to be unclear. 5 Q. Well -- 6 MR. FREEMAN: You say it was changed, 7 and not necessarily submitted in the same form. 8 Q. Well, for instance, data 9 concerning adverse events, some data was 10 submitted to investigators to Lilly in a manner 11 that was compiled into a summary form and then 12 submitted to the Food and Drug Administration, 13 correct? 14 MR. FREEMAN: Does the question imply 15 that underlying data was not sent? 16 MR. SMITH: No, it implies exactly how 17 it read, it was supplied to Lilly and then 18 submitted in a different form to the Food and 19 Drug Administration, such as a summary. 20 MR. FREEMAN: Do you understand? 21 A. It's one of those questions 22 that, I'm sorry, I just can't answer with a yes 23 or no. May I comment? 24 Q. Certainly. Page 147 1 A. The vast majority of the 2 material that came to Lilly from investigators 3 came in the form of completed case report forms. 4 Q. Uh-huh. 5 A. So over the course of studies, 6 of course, became extremely voluminous. Some 7 case report forms were submitted early, prior to 8 the NDA being submitted, I believe, I can't be 9 absolutely sure of that point. When we submitted 10 the New Drug Application, the case report forms, 11 I believe, were sent in on microfiche. Although 12 we -- I mean a hard copy would be provided at 13 such time as the FDA wished. I believe that was 14 the procedure on that NDA. So in answer to your 15 question, if an investigator had sent in ten case 16 report forms, ultimately those case report forms 17 went to FDA on microfiche. 18 Q. All right. But if those ten 19 case report forms had a particular, say, three 20 particular adverse experiences or adverse events 21 reported -- 22 A. Okay. 23 Q. -- those would be also 24 submitted to the Food and Drug Administration in Page 148 1 a separate form, would they not? 2 A. In the form of tabulations and 3 analyses and so forth, yes. 4 Q. That was -- those tabulations 5 and analyses were done by Lilly, were they not? 6 A. Yes, but much of that was 7 done, and I'm unclear as to details here, Mr. 8 Smith, but much of that, I believe, was done with 9 Lilly personnel blinded as well as the 10 investigator and the patient. 11 Q. I understand that, I'm not 12 suggesting that it was unblinded, but the mere 13 point I'm making is data was sent to Lilly to the 14 investigator -- by the investigators? 15 A. Correct. 16 Q. Data was sent by the 17 investigators to Lilly, correct? 18 A. Correct. 19 Q. Volumes? 20 A. Yes. 21 Q. Voluminous data? 22 A. Yes. 23 Q. And that -- a lot of that data 24 was submitted to the FDA in microfiche forms, the Page 149 1 actual case report forms that recorded actual 2 patient by patient, visit by visit information, 3 correct? 4 A. Yes. 5 Q. And that was sent on 6 microfiche for a reason, was it not? 7 A. Just the sheer volume, yes. 8 Q. The sheer volume -- there 9 wouldn't be room at the FDA for that all that 10 material, number one? 11 A. I know, I've sat there. 12 Q. Number two, the FDA doesn't go 13 through each one of those case report forms, do 14 they? 15 A. I did. 16 Q. When you were at the FDA, you 17 went through each and every case report form that 18 was submitted on a drug? 19 A. Yes. 20 Q. After you left, do you know of 21 anybody that did? 22 A. No. I didn't ask the 23 question, but -- 24 Q. What's your opinion concerning Page 150 1 whether or not each and every case report form 2 that was submitted by Eli Lilly and Company to 3 the Food and Drug Administration in connection 4 with Prozac was actually reviewed by somebody at 5 the FDA? 6 A. Probably didn't happen. 7 Q. Simply by virtue of the sheer 8 volume. 9 A. Yes. 10 Q. Would you agree that the FDA 11 is overworked and understaffed? 12 A. Yes. 13 Q. And that the FDA has to rely 14 on the sponsor, the pharmaceutical manufacturer, 15 for some help in evaluating the safety and 16 efficacy of a drug? 17 A. Yes. 18 Q. And that's based on your 19 experience not only as an individual who has 20 worked with the Food and Drug Administration, but 21 as an individual that's worked for two separate 22 pharmaceutical firms, correct? 23 A. Yes. 24 Q. Additionally, the FDA system Page 151 1 of examining a drug for safety and efficacy can 2 only be as good as the information that it gets, 3 correct? 4 A. I was hung up on your word 5 system, I'm not entirely convinced that there is 6 one. 7 Q. Is it that disorganized? 8 A. Sometimes, yes. 9 Q. Well, use a term that you're 10 comfortable with. 11 A. Process, procedures, whatever, 12 that isn't the important point. FDA reviewers -- 13 I'm not suggesting that they play got-ya games, 14 but by the same token they are not adverse to 15 raising questions, auditing, reanalyzing, 16 inspecting, et cetera. In other words they're 17 carrying out their regulatory function to the 18 best of their abilities. 19 Q. But sometimes they'll play 20 got-ya in an area that doesn't need to have 21 inquiry, correct? 22 A. I've known that to happen, 23 yes. 24 Q. And sometimes they'll miss an Page 152 1 area that does need inquiry, won't they? 2 A. Well, if that's later 3 discovered, then it must not have been missed. 4 Q. All right. But you -- you 5 have reason to believe, based on your working at 6 the FDA and working for pharmaceutical firms, 7 that sometimes there's some area that actually 8 could deserve closer scrutiny by FDA employees, 9 that just by virtue of the FDA is made up of 10 human beings doesn't get looked at, right? 11 A. This, I have to agree, is 12 possible. 13 Q. Now, would it be accurate to 14 state that there are other safeguards or other 15 procedures in place by FDA regulations that also 16 help in the process of identifying risks 17 presented by particular drugs? And by that I'm 18 speaking about a post-marketing surveillance 19 system. 20 A. That is a means of gaining 21 additional information, yes. 22 Q. In other words, if there is a 23 requirement, which there is, that adverse 24 experiences that -- or adverse reactions that are Page 153 1 made known to a pharmaceutical manufacturer are 2 made known to the FDA, then there might be a 3 greater body of knowledge concerning a particular 4 adverse event than is revealed by the clinical 5 trial process? 6 A. Please excuse me, I got sort 7 of lost. 8 Q. I got kind of lost when I was 9 asking it, really, Doctor Dobbs. In other words 10 FDA law requires that if a manufacturer hears of 11 an adverse event in connection with its product, 12 that it advise the FDA of that particular adverse 13 event, correct? 14 A. Yes. Some are required to be 15 submitted rapidly and others are not. 16 Q. There's different times within 17 which to report different types of events, but -- 18 A. Yes. 19 Q. -- the theory is that if a 20 manufacturer learns that its product is the 21 subject of a particular adverse event, that that 22 manufacturer must tell the government about it? 23 A. I would have to quibble a 24 little bit with your wording. If a manufacturer Page 154 1 learns that an adverse event has been reported in 2 association with one of that manufacturer's 3 drugs, it must -- the report must be submitted 4 sooner or later to the Food and Drug 5 Administration. 6 Q. Correct. 7 A. Without any elimination by 8 virtue of anybody's conclusion. 9 Q. I understand. Now, that's not 10 a requirement of a physician, though, is it, that 11 if you suspect as a medical doctor that a 12 particular medication has caused a particular 13 adverse event, that you report your findings to 14 the United States Food and Drug Administration, 15 correct? 16 A. The Food and Drug 17 Administration has no statutory authority over 18 the practice of medicine. 19 Q. So you don't -- if a 20 particular doctor sees an adverse event, it 21 doesn't mean he has to report it to the FDA, does 22 it? 23 A. Correct. 24 Q. And you know that in fact Page 155 1 physicians are not uniform in reporting adverse 2 events to the Food and Drug Administration, don't 3 you? 4 A. Nor would it be desirable if 5 they did in most instances. 6 Q. Why would that be undesirable, 7 Doctor Dobbs? 8 A. Because you, just a moment 9 ago, asked me, and I agreed, whether FDA is 10 already understaffed and overworked, et cetera. 11 And then suppose every physician in the country 12 who has prescribed, let's just say, Drug X, and 13 who encounters something quite minor which was 14 already well recognized and included in the 15 package insert, reporting that sort of situation 16 would be a total waste of the physician's time, 17 the FDA's time -- 18 Q. You're probably correct, that 19 that would result in an over-reporting, wouldn't 20 it? 21 A. Yes. 22 Q. But if it were an adverse 23 effect that was serious and was not known or had 24 not been contained in the package insert, then Page 156 1 you, as an ethical physician and as an individual 2 who had worked for the Food and Drug 3 Administration and for the pharmaceutical 4 industry, would think that that probably is a 5 situation where there should be reporting for 6 safety of patients in general? 7 A. If I can assume that your term 8 serious means clinically serious, and not 9 previously recognized, then I would feel 10 obligated to report. 11 Q. Yes, ma'am, that's what I 12 implied by my question. Therefore -- well, would 13 you agree -- I've seen some data indicating that 14 ten percent of adverse experiences reported by 15 physicians are actually reported, in other words 16 that maybe ninety percent of adverse experiences 17 seen by a physician are not reported to the Food 18 and Drug Administration? 19 A. For no scientific reason 20 whatsoever, the figure of ten percent seems high 21 to me. 22 Q. All right. You would think it 23 was even less? 24 A. Yes, for the reasons that I've Page 157 1 already illustrated. 2 Q. The reason that the Food and 3 Drug Administration is in the business of 4 collecting reports of adverse events and in the 5 business of requiring reports of adverse events 6 from manufacturers, isn't it so that there can be 7 another body of evidence concerning a particular 8 side effect profile of a particular medication 9 over and above that body of evidence that's 10 developed during the clinical trial process? 11 A. Again, I got just a little bit 12 lost, Mr. Smith, and I'm sorry. Certainly when 13 you speak of a profile, that term to me implies 14 incidence figures. 15 Q. Okay. 16 A. And certainly random -- well, 17 not random, but occasionally physicians can't 18 provide any information on actual incidents, you 19 might have a numerator and no denominator for 20 that. That wouldn't help in any profile as I've 21 used the term. If one is looking -- let me start 22 all over. In the process of carrying out their 23 surveillance mission on marketed drugs, FDA has a 24 general concern, in addition to profile, to the Page 158 1 occurrence of rare events. And for that kind of 2 thing, the individual physician reports would be 3 useful. 4 Q. All right. 5 A. If well documented. 6 Q. And even events that are not 7 serious, the FDA requires the manufacturer to 8 report in a certain period of time a higher 9 incidence of a particular adverse experience? 10 A. I believe that is in the -- I 11 believe that's in the regulations which became 12 effective while I was still at FDA. 13 Q. All right. And the reasoning 14 for that is what? 15 A. I don't really know what was 16 entirely -- what was behind that, I suppose as a 17 general thought as a check to see if current 18 experience in any way is different from that 19 reported in the clinical trials. However, I have 20 a recollection of thinking when I say that that a 21 supposed reaction, a possible reaction reported 22 by an isolated physician and maybe another 23 physician and another physician, still doesn't 24 give an incidence figure and so if you have no -- Page 159 1 I remember thinking, how on earth can the 2 manufacturer necessarily recognize an increased 3 incidence except in the context of a clinical 4 trial. I was as wordy as some attorneys I have 5 met for which I ask your apology. 6 Q. I guess the point I was 7 driving at, and obviously I'm trying to make some 8 points, Doctor Dobbs, but in the interest of 9 developing what happens accurately, the sponsor 10 or manufacturer's clinical trial data is somewhat 11 limited, is it not? 12 MR. FREEMAN: The manufacturer's 13 clinical trial data? 14 MR. SMITH: Clinical. Did I say -- 15 MR. FREEMAN: You said manufacturer's 16 clinical trial data. 17 Q. The data generated by the 18 manufacturer, vis-a-vis clinical trial data, is 19 somewhat limited, is it not? 20 A. I'm sorry, I don't really know 21 what you mean by limited. 22 Q. Well, we know that the 23 protocols in connection with Prozac included 24 individuals with certain criteria, and excluded Page 160 1 individuals with certain criteria. 2 A. That's correct. 3 Q. Allowed for some medications 4 to be used concomitantly, and disallowed some 5 medications being used concomitantly. 6 A. Yes. 7 Q. So from that aspect, you're 8 not going to get as broad a spectrum of patients 9 in the clinical trial data as you might expect to 10 get in the actual post-marketing practice, 11 correct? 12 A. Correct. 13 Q. So you'll have a greater 14 number of patients exposed to the product after 15 the clinical trials, won't you? 16 A. Yes. 17 Q. And the post-marketing data 18 will be reflective of that larger group of 19 patients, will it not? 20 A. Yes. 21 Q. And most physicians don't 22 know, in connection with any particular drug, 23 what particular patients were included and 24 excluded in the clinical trial process, do they? Page 161 1 A. The major trials would be 2 reflected in publications ordinarily, and that of 3 course is open to scrutiny by anyone. 4 Q. But, for instance, Prozac is 5 prescribed by a lot of physicians who are general 6 practitioners, correct? 7 A. I would assume so, I don't 8 know it for a fact. 9 Q. If you'll assume with me, our 10 discovery to date has indicated that at this time 11 far more general practitioners are prescribing 12 Prozac in numbers than psychiatrists are, and I'm 13 sure you're aware of that. 14 A. I have no reason to question 15 your statement. 16 Q. So, you wouldn't expect most 17 of the general practitioners that have prescribed 18 Prozac to be familiar with the scientific 19 literature concerning clinical trials done on 20 Prozac, would you, at least not -- 21 A. As an assumption, I would take 22 it that most general practitioners couldn't, as a 23 matter of time, read literature in a wide variety 24 of fields, in depth. Page 162 1 Q. So it might very well be that 2 those general practitioners are giving Prozac to 3 patients who are depressed, that those particular 4 patients might have been excluded from a Lilly 5 clinical trial? 6 A. That's possible. 7 Q. I can't think of a particular 8 instance now, but generally speaking, in this 9 practice, you expect that a broader group of 10 patients to be receiving the product post-market 11 than during the clinical trial phase, do you not? 12 A. Yes. 13 Q. And that's known by the 14 manufacturer? 15 A. Yes. 16 Q. And it's known by the Food and 17 Drug Administration, is it not? 18 A. Yes. May I add something to 19 my answer? Some of the questions are 20 specifically addressed in other contexts. For 21 example, in most efficacy trials there is an 22 upper age limit, however FDA expects to see, and 23 most manufacturers would conduct without being 24 asked, some investigation in elderly patients. Page 163 1 They would frequently -- I don't remember exactly 2 what Lilly did in the case of fluoxetine. They 3 would probably try the drug in a carefully 4 supervised fashion in patients with impaired 5 renal capacity or with impaired liver function, 6 at least to the extent of blood levels. So some 7 of the questions that arise out of limitations 8 from the major protocols are addressed. Can one 9 address every single possible concurrent medical 10 condition, no, of course not. 11 Q. That's not what I'm 12 suggesting, I'm only suggesting that 13 post-marketing data, as collected by the Food and 14 Drug Administration, generally will encompass a 15 larger number of patients and a broader spectrum 16 of patients, will it not? 17 A. Certainly a broader spectrum. 18 The actual numbers, considering that most adverse 19 experiences or suspected adverse experiences go 20 unreported, I don't know. It might take quite a 21 while for spontaneous reports to equal in number 22 the clinical population within the studies. 23 Q. All right. So it might be 24 that there might be a particular event that Page 164 1 wouldn't be picked up in post-marketing reports 2 that would be picked up in the clinical trial 3 phase? 4 A. That's possible. 5 Q. Maybe because it was 6 specifically looked for in the clinical trial 7 phase? 8 A. Perhaps. 9 Q. Obviously clinical trials are 10 done as per protocols, are they not? 11 A. One hopes so, yes. 12 Q. And in protocols -- is my 13 understanding correct that a protocol for a 14 pivotal trial must be approved by the Food and 15 Drug Administration before the clinical trial is 16 begun or can it be approved subsequent to the 17 trial being done? 18 A. At the time I was at Lilly, 19 there was no regulatory requirement that 20 protocols for those studies intended to be 21 pivotal have prior approval. FDA encouraged 22 submission of such protocols and discussion 23 thereof, however it could sometimes take six 24 months or a year to get such a meeting. Page 165 1 Q. All right. 2 A. So the practical effects were 3 arguable. 4 Q. So sometimes the trial might 5 have been underway before there was actual 6 official FDA approval? 7 A. Yes, and sometimes there never 8 was official FDA approval. Ultimately if the 9 drug itself is approved, I suppose that 10 constitutes tacit approval of the more important 11 protocols. 12 Q. Okay. But the protocol, at 13 least from the manufacturer's standpoint, and to 14 some extent from the Food and Drug 15 Administration, is designed to look at specific 16 issues with respect to the specific drug? 17 A. To a large degree, that's 18 true, however the collection of adverse reaction 19 information is designed so that if someone 20 notices, to be absurd, a purple toad, that can be 21 reported. 22 Q. I understand that. But as far 23 as the design of the clinical trial, it's 24 generally designed as per a protocol, that is the Page 166 1 protocol itself is designed to look at a specific 2 issue in connection with the drug under 3 investigation. For instance, you do a study on 4 geriatric patients -- 5 A. Yes. 6 Q. -- that would be a situation 7 where it's designed to look at a specific issue 8 or issues? 9 A. Yes. 10 Q. Obviously in the Prozac 11 protocols, they required that a number of the 12 individuals, if not all of the individuals, be 13 suffering from depression, since that was the 14 indication for which the product was being 15 submitted? 16 A. Yes. 17 Q. Did you know that the clinical 18 trials were not designed to examine the issue of 19 suicidality? 20 MR. FREEMAN: Are you talking about 21 the majority of them? 22 MR. SMITH: Any of the protocols -- 23 any of the clinical trials done before FDA 24 approval. Page 167 1 A. The clinical trials -- setting 2 aside special populations, the clinical trials 3 were intended to assess safety and efficacy, 4 efficacy as defined by changes in certain rating 5 scales, safety as defined by measurements of 6 vital signs, electrocardiograms, laboratory 7 studies, and such adverse events, not necessarily 8 caused by, and all adverse events reported by the 9 investigators. 10 Q. I understand that. 11 A. So, was a trial specifically 12 designed to study suicide ideation, suicide 13 intent, suicide attempts or suicide, no, but 14 clearly that fell under the umbrella of studies 15 that were designed to assess safety. 16 Q. Let me ask you then, did the 17 issue, while you were working for Eli Lilly and 18 Company, ever come up concerning whether or not 19 fluoxetine hydrochloride had any effect, 20 positively or negatively, on depressed 21 individuals and their suicidality? 22 A. Please excuse me, I keep 23 backing away from the term suicidality because 24 I'm not comfortable with the term. Page 168 1 Q. Okay. Can you give me a term 2 that you're comfortable with and I'll certainly 3 use that? 4 A. Suicidal tendencies comes to 5 mind, and I'm not sure that that's much of an 6 improvement. But if we can say that, for 7 purposes of this session, suicide tendencies 8 refers to suicidal ideation, suicidal gestures, 9 suicidal attempts, suicide, then maybe we can 10 talk about the same thing. And now I've 11 forgotten the question. 12 Q. The question was, did the 13 issue of whether or not Prozac had any effect on 14 depressed individuals and their suicidal 15 tendencies ever come up while you were at Eli 16 Lilly and Company? 17 A. Yes. 18 Q. Okay. When did that come up 19 or when was that raised? 20 A. I can't date that. We 21 recognized, of course, from the outset that 22 suicidal tendencies are a part and parcel of 23 depressive illness, and that, therefore, patient 24 population, regardless of what they were Page 169 1 receiving in the studies, had some potential for 2 that. Scattered reports came in, we talked 3 informally as one does in, you know, in the 4 hallway, and this person's office, we probably 5 had formal meetings, I can't remember them at 6 this late date. I'm sure we examined incidence 7 figures with fluoxetine and placebo and other 8 drugs. 9 Q. Anything else? 10 A. Not that occurs to me at the 11 moment. 12 Q. How did the subject come up? 13 A. I believe because of scattered 14 isolated reports. Perhaps some may have been 15 from overseas, I'm not sure of that point. 16 Q. All right. So it might have 17 come from overseas -- are you saying it might 18 have come as adverse experience reports from the 19 investigators? 20 A. Possibly. 21 Q. So what was done about it, you 22 say you talked informally? 23 A. And I also said that we 24 probably had meetings of the people involved. I Page 170 1 can't remember them, but then I haven't been able 2 to remember lots of other circumstances we've 3 talked about today. 4 Q. Do you have any specific 5 recollection of talking with anybody at Eli Lilly 6 and Company on an informal basis, Doctor Dobbs, 7 concerning suicidality or suicidal tendencies 8 that occurred during the clinical trials? 9 A. I have a mental picture of 10 talking to Mrs. Earlene Ashbrook. I'm sure that 11 wasn't the only discussion, and I don't know why 12 that happens to come to mind. 13 Q. Anyone else? 14 A. Not that I can conjure up as 15 an image at this moment. 16 Q. You said you probably had 17 formal meetings in connection with this issue. 18 Were you a part of any of those formal meetings 19 or is that just an assumption on your part, 20 Doctor Dobbs? 21 A. It's -- I guess it's an 22 assumption, yes. 23 Q. Because you can't remember any 24 formal meetings? Page 171 1 A. I can't actually remember any 2 formal meetings, correct. 3 Q. You say you might have 4 examined the incidence figures concerning 5 suicidal tendencies or is that also an assumption 6 on your part or do you specifically recall doing 7 that? 8 A. It's somewhere between. I 9 have a vague recollection of doing that. 10 Q. All right. Do you recall what 11 the examination of the incidence figures 12 revealed? 13 A. Not in any detail, no. 14 Q. Do you recall where you got 15 those incidence figures? 16 A. Ms. Ashbrook was probably 17 responsible for providing those. 18 Q. Is that something that you 19 requested she provide you or you're just aware 20 that she provided that to somebody? 21 A. I'm not sure. I may have 22 requested it, but someone else may have requested 23 it. 24 Q. But I think you said you don't Page 172 1 recall what the figures revealed? 2 A. I said I didn't remember the 3 figures. By the same token -- and there's a 4 degree of assumption in this -- I don't remember 5 feeling that -- correction, I don't remember 6 concluding, in my own mind, that fluoxetine was 7 associated with any greater incidence of suicide 8 tendencies than placebo or other drugs. 9 Q. All right. 10 A. In other words, it seems to me 11 that if I had concluded otherwise, my concern 12 would have been heightened and I would have 13 remembered. 14 Q. All right. Now would I be 15 accurate in stating, Doctor Dobbs, that -- you 16 said earlier that you expected a higher incidence 17 of suicidality among depressed individuals, is 18 that correct? 19 A. A higher incidence than were I 20 to stop the next five hundred people on Route 7 21 out there, yes. 22 Q. Depressed people are more 23 likely to have suicidal tendencies than 24 nondepressed individuals? Page 173 1 A. Yes. 2 Q. So can I assume from that that 3 the fact that any particular case report form 4 indicated that a particular patient was reporting 5 suicidal tendencies wouldn't necessarily alarm 6 you any more than that type of information would 7 alarm a psychiatrist? Do you follow what I'm 8 saying? 9 A. I think so. I don't believe 10 that I was callous, I don't believe that anyone 11 there was callous. We recognized the potential 12 anytime one conducts such studies, but an 13 isolated report, for example, that some patient 14 had expressed suicidal thoughts would not have me 15 actually alarmed, correct. 16 Q. Because it's part of your 17 training learned that suicidality is something 18 that can be seen in individuals suffering from 19 depression? 20 A. Yes. Also I'm aware that 21 expression of suicidal thoughts taken alone can 22 have many underlying causes. It can be merely 23 manipulative, it can be fleeting, and of little 24 or no clinical significance. Page 174 1 Q. But no psychiatrist treats 2 that lightly, at least on the face of it, do 3 they? 4 A. Correct. 5 Q. In other words, you're trained 6 to exercise your clinical judgment to make an 7 intelligent decision concerning whether or not 8 that's acting out or actually a real and imminent 9 threat, correct? 10 A. We certainly try to do that, 11 we don't do it perfectly. 12 Q. Have you treated anyone who is 13 suicidal, Doctor Dobbs? 14 A. Yes. 15 Q. In your period as a 16 psychiatrist? 17 A. Yes. 18 Q. And do you consider that one 19 of the most serious problems presented to a 20 psychiatrist, that is suicidal tendencies in 21 depressed individuals? 22 A. Well, I've also known some 23 homicidal patients, but either was an issue of 24 life or death. Page 175 1 Q. And you do recognize that 2 these are the most serious of most psychiatric, 3 at least among the depressed patient population? 4 A. Yes. 5 Q. No psychiatrist, and that's -- 6 no psychiatrist wants to be treating a patient 7 who commits suicide and had expressed earlier a 8 threat of that, correct? 9 A. Correct. 10 Q. And certainly you try to use 11 your best judgment to make a determination 12 whether or not those threats are indeed real? 13 A. Yes. 14 Q. And if there is any question 15 about it, you want to do something, you, the 16 psychiatrist wants to take some action in 17 connection with those threats, correct? 18 A. Yes. 19 Q. If you're going to err in that 20 situation or if you're going to over -- if you're 21 going to do something, you're going to want to 22 over treat as opposed to under treat that type of 23 threat? 24 A. Yes. Page 176 1 Q. For instance, if a decision of 2 hospitalization is fifty-fifty, if somebody is 3 indicating suicidal tendencies, it would be 4 better off to hospitalize them than not in most 5 instances? 6 A. It would, but for some of the 7 sad facts of our current health care system, when 8 hospitalization, private hospitalization may be 9 impossible, and state hospital hospitalization 10 leaves much to be desired qualitatively, and in 11 any event the patient is likely to be discharged 12 three days later. 13 Q. All right. In connection with 14 this issue of suicidality, and how it came up, we 15 have shown you an exhibit, I don't know which 16 it's marked -- Exhibit 3. This document, this 17 Telex from Germany that you weren't addressed on, 18 an issue from the BGA, turn to point fourteen. 19 It says, as we've already explained -- as we 20 already explained by our Telex to Doctor Zerbe, 21 June 8th of '84, we need a careful analysis of 22 suicides and suicide attempts, patient by 23 patient, symptomatology, and severity upon entry 24 into the study, and week by week until the event Page 177 1 occurred, dose of fluoxetine, side effects, et 2 cetera. This is a very serious issue in the 3 opinion of the BGA. It might well be that we 4 have to recommend concomitant tranquilizer intake 5 for the first two or three weeks in the package 6 literature, end quote. Did I read that 7 correctly? 8 A. Yes. 9 Q. As I understand it, you have 10 not seen this before? 11 A. I think I may have seen it 12 while I was at Lilly, I'm not sure. 13 Q. Would that be the first 14 instance that you were aware of where there might 15 have been some -- you said you might have had 16 some overseas information that came in concerning 17 the issue of Prozac and suicidality. Could this 18 be what we're talking about? 19 A. I simply don't know, I -- let 20 me see the date. 21 Q. This is June, '84. 22 A. No. Based on the date, my 23 best estimate is that the informal chats and 24 possibly formal meetings and concerns and so Page 178 1 forth occurred prior to this. 2 Q. All right. And -- 3 A. And may have been ongoing, I 4 don't know. 5 Q. Do you know of any memos, 6 notes, data of anything in that connection? 7 Because this is about the first time we've seen 8 it from any document. 9 A. I could be totally wrong in my 10 estimate. You know, I'm trying to be as truthful 11 as possible. 12 Q. I understand that. 13 A. It might have been the first, 14 my best estimate is that it was not. 15 Q. All right. Do you recall ever 16 discussing with Doctor Zerbe this issue of 17 suicidality? 18 A. I have no specific 19 recollection of discussing it with Doctor Zerbe. 20 Q. Turn back to page two of the 21 document, item ten. It says the BGA suspects 22 fluoxetine to be a stimulating activating drug. 23 A. Excuse me, I must have 24 misunderstood. Page 179 1 MR. FREEMAN: Page two. 2 Q. Page two, item ten, the last 3 sentence, reason, the BGA suspects fluoxetine to 4 be a stimulating activating drug, paren, side 5 effect profile, suicide, suicide attempts, close 6 paren, period. Do you see that? 7 A. Yes. 8 Q. Had you heard before this that 9 Prozac could be a stimulating activating drug? 10 A. I think I've already testified 11 that I never would have characterized it as being 12 a stimulating drug, recognizing that there was a 13 percentage of patients that experience 14 nervousness, nor would I have used the term 15 activating, whatever that means. 16 Q. Do you as a psychiatrist and a 17 scientist recognize a side effect profile of 18 suicide and suicide attempts in connection with 19 stimulating activating drugs? Is that known, 20 that stimulating activating drugs have a higher 21 incidence of side effect profile of suicides and 22 suicide attempts? 23 A. I'm not aware of that if it's 24 true. I was trying to think what drugs I would Page 180 1 regard as stimulating or activating amphetamines, 2 for example, I don't recall that they are 3 associated particularly with suicide attempts. I 4 don't know whether there are data on that 5 question or not. 6 Q. Do you know Doctor Jan 7 Fawcett? 8 A. I've heard the name. 9 Q. He's on Lilly's psychiatric 10 advisory board. Do you have -- have you ever 11 read anything he said concerning Prozac and 12 jitteriness, nervousness, therefore presenting a 13 risk in suicidal patients requiring concomitant 14 tranquilizers? 15 A. If I've read anything that he 16 wrote, I didn't -- I couldn't identify it now, I 17 don't remember it. 18 Q. Do you know of anything that 19 was done in connection with Exhibit 6, yourself, 20 that is whether or not there was this analysis of 21 suicides and suicide attempts as requested by 22 item fourteen on page three? 23 A. Excuse me, I thought you said 24 Exhibit 6? Page 181 1 Q. I'm sorry, it is Exhibit 3. 2 It was Exhibit 6 to another deposition. 3 A. All right. Now that we've 4 straightened out that critical point -- 5 Q. Do you know whether or not 6 anything was done in connection with this June 7 26, '84 Telex concerning those issues raised in 8 item fourteen of the analysis that needed to be 9 done? 10 A. I'm virtually certain that 11 something was done, if only because the practice 12 within Lilly Indianapolis was to respond to 13 requests from affiliates. 14 Q. Why were you not -- 15 A. Specifically I can't tell you 16 how we responded to any of the items. 17 Q. Why would you not have been 18 included in this document, Doctor Dobbs, since 19 you are a psychiatrist, medical doctor, who was 20 the medical regulatory scientist involved with 21 Prozac at the time? 22 A. I have no idea. 23 Q. Wasn't this something that 24 would come under your purview normally? Page 182 1 A. Yes. 2 (PLAINTIFFS' EXHIBIT NO. 9 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. While he's say looking at 6 that, did you ever have the feeling, Doctor 7 Dobbs, that you were taken out of the loop or 8 somehow there was some information while you were 9 an employee at Eli Lilly and Company that you 10 should have had that you didn't receive? 11 A. With respect to whether I was 12 taken out of the loop, that feeling crossed my 13 mind. But with respect to the other half of your 14 question, I have no specific reason to believe 15 that information was withheld from me and, 16 therefore, from Food and Drug Administration. 17 Q. Certainly that information 18 reflected in Exhibit 3 that the BGA expected 19 Prozac to be an activating drug and that the BGA 20 was concerned about this issue was not brought to 21 your attention, was it, Doctor Dobbs? 22 A. As I have already testified, I 23 think I probably saw this, regardless of the fact 24 that it was not specifically addressed to me. I Page 183 1 may have been involved in the response. 2 Q. Did you, as the regulatory 3 scientist involved at the time, forward that on 4 to the Food and Drug Administration for their 5 review? 6 A. This Telex? 7 Q. Yes, ma'am. 8 A. If I heard your question 9 correctly, it was did I ask the regulatory 10 scientist -- 11 Q. Did you as the regulatory 12 scientist. 13 A. Oh, I beg your pardon. I 14 probably would not have submitted this Telex. As 15 I said, I think I probably saw it. I probably 16 would not have submitted it, not as a matter of 17 concealing something, but because this is simply 18 expressing an opinion of someone -- or more than 19 one, perhaps, individual at BGA, which individual 20 or individuals are simply looking at data already 21 in the hands of the Food and Drug Administration. 22 I don't think this would have added anything, so 23 I probably didn't submit it. 24 Q. Okay. Look at Exhibit 9, Page 184 1 then, and see if you can tell me if you think 2 that the BGA is looking at the same data that the 3 FDA is. 4 A. Yes. 5 Q. You were still with Lilly in 6 April, 1985, were you not? 7 A. Yes. 8 Q. Which is the time this 9 document was generated apparently? 10 A. Yes. 11 Q. Were you familiar with this 12 problem in Germany in connection with 13 registration of Prozac as Fluctin in Germany? 14 A. I certainly have no specific 15 recollection of this memo. And this instance -- 16 I'll make a little more than a guess, I suppose, 17 that I might not have seen this. 18 Q. Why do you suppose that, 19 Doctor Dobbs? 20 A. Because of the date. 21 Q. All right. 22 A. As I left about two months 23 later and as I have already acknowledged, there 24 were some times when I felt a bit out of the Page 185 1 loop. 2 Q. All right. And you think this 3 might be something that by virtue of the fact 4 that you felt out of the loop and were going to 5 be leaving in two months -- 6 A. Although no one at Lilly knew 7 that at that time, this is conjecture. 8 Q. But you were the regulatory 9 scientist in connection with Prozac in April, 10 1985, were you not? 11 A. Yes. 12 Q. But you were not made aware of 13 this particular Telex from Germany? 14 A. Well, obviously my name does 15 not appear among the addressees. 16 Q. Well, Doctor Dobbs -- 17 A. That was the case with the 18 earlier communication, where my very, very vague 19 recollection is that I probably saw it. In this 20 case, I doubt that I saw it, but I can't be 21 certain. 22 Q. Because you think you would 23 have remembered it had you seen this, don't you, 24 frankly, Doctor Dobbs? Page 186 1 A. Perhaps, yes. 2 Q. Because of the statement here, 3 still not resolved is the fact that suicide 4 attempts have been observed more frequently on 5 fluoxetine as compared to imipramine. Only 6 epidemiologic data or literature for other 7 antidepressants may help to identify whether it 8 happened by chance that incidence of suicide 9 attempts was abnormally high on fluoxetine or 10 abnormally low on comparitors, end quote, 11 correct? 12 A. Yes, that's what it says. 13 Q. Were you aware, Doctor Dobbs, 14 as the regulatory scientist at Lilly, that there 15 was a German consultant who had found the 16 incidence of suicide attempts in Germany in the 17 imipramine versus fluoxetine trial higher on 18 fluoxetine than imipramine? 19 A. I don't remember being made 20 aware of this, and in any event, this statement, 21 if I saw it, I would not have regarded it as the 22 last word, and sitting here today, I do not 23 regard it as the last word. 24 Q. Certainly, as this document Page 187 1 reflects, this is a summary, isn't it, of what 2 this expert opinion reflected, isn't it? 3 A. Yes -- well, I trust that it's 4 an accurate summary. 5 Q. Well -- 6 A. I don't know. 7 Q. The last sentence of the first 8 page says outcome, Professor Blank left an 9 opinion of twenty-one typewritten pages. The 10 essential points are summarized as follows, 11 colon, and then they go ahead, apparently, and 12 summarize what that twenty-one page report was, 13 don't they? 14 A. Johanna purported to be doing 15 that. 16 Q. Yes. And whether or not she 17 summarized those reports favorably to Lilly or 18 favorably to Doctor Herrmann or she gave it 19 accurate summaries, we don't know from reading 20 this, do we? 21 A. We don't know. 22 Q. And have you ever seen the 23 actual twenty-one page report, Doctor Dobbs? 24 A. Not that I can remember. Page 188 1 Q. Have you ever heard of a 2 twenty-one page typewritten report done by Doctor 3 Herrmann or any other consultant in Germany in 4 connection with the registration of Prozac in 5 Germany and the issue of suicidality as raised by 6 the imipramine trials? 7 A. As I have already indicated, I 8 have no recollection of this memo. I may have 9 seen it, I think I probably did not, I have no 10 recollection of a report by Doctor Herrmann, I 11 can't be certain whether I ever saw it. 12 Q. Would this report be 13 something, as the regulatory scientist involved 14 with Prozac, that should or you would have sent 15 to the United States Food and Drug 16 Administration? 17 A. It's awfully hard to make sure 18 what one would have done ten or eleven years ago 19 or whatever. My reaction today, if I tried to 20 imagine myself back in that setting, is that I 21 would not submit these pages. I would request, 22 rapidly, perhaps certain other aspects of this. 23 But at the least, this higher incidence 24 paragraph, I would request information behind Page 189 1 that, what were they going back to raw data, what 2 were the actual figures, how long was the patient 3 on the drug, how long was the patient on the 4 comparitor drug, what differences were there in 5 the patient populations at entry, and on and on 6 and on. Which isn't to say I would foot drag for 7 months, but I would not submit a third-hand 8 opinion on something that I hadn't seen. 9 Q. Well, are you saying that you 10 would have submitted the opinion itself, though, 11 in other words this is third hand because this is 12 summarizing Doctor Herrmann's report, correct? 13 A. I don't really know whether I 14 would, in this hypothetical or imaginary 15 situation, whether I would submit this or not. 16 This, after all, is prepared by Doctor Johanna 17 Schenk. 18 Q. Do you know her? 19 A. I did. 20 Q. All right. 21 A. I don't recall what doctor it 22 refers to. I feel virtually certain that Johanna 23 was not a physician and not a psychiatrist. I 24 would, at the least, have gone back to Doctor Page 190 1 Herrmann's report, but I would have ordered the 2 information that I just outlined. 3 Q. First thing you would have 4 done, I believe you said, was you would have 5 ordered the report sent to you immediately, would 6 you not? 7 A. I think I would have, yes. 8 Q. Had you known of its existence 9 and had you known that it was being summarized 10 with this -- in these terms, the first thing you 11 would have done as the regulatory scientist 12 involved, had you known about this, would have 13 been to ask for the report immediately, correct? 14 A. I believe so. 15 Q. That's because you've got to 16 see the report itself to really understand the 17 true significance of the summary here, correct? 18 A. Basically a summary of a 19 summary, yes. 20 Q. This is three pages, the 21 opinion is twenty-one pages. If for no other 22 reason, the length would indicate that it's going 23 to have more details, correct? 24 A. Yes. Page 191 1 Q. And it might very well have 2 that information that you said you would be 3 impressed with concerning how long these people 4 had been on the medication, details of the 5 particular individuals, and things of that 6 nature, correct? 7 A. Yes. 8 Q. If that were the case, that 9 probably would be something that you would have 10 and should have submitted to the Food and Drug 11 Administration, correct? 12 A. Unless upon -- well, if upon 13 review we, not just I alone, we had concluded 14 that this conclusion was not supported by the 15 actual facts, then I wouldn't be in any big 16 hurry, setting aside the other issues, I wouldn't 17 see any need to submit rapidly, and I would sleep 18 very well that night, that is my acute concerns 19 would be lessened markedly. Would the report 20 need to be submitted at some point given those 21 circumstances, we have concluded that there's 22 nothing to it for the following reasons or that 23 it's a fallacious conclusion, would really 24 depend. Is it simply somebody else's reanalysis Page 192 1 of information that has already gone in, that 2 becomes a debatable issue. 3 Q. Does the fact, Doctor Dobbs, 4 that this twenty-one page opinion is somebody 5 that was hired by Lilly to, as it says here, 6 quote, to give best advice as a consultant to the 7 company in the registration process of 8 fluoxetine, end quote, would that have a 9 significance in whether or not it should be 10 submitted to the United States Food and Drug 11 Administration, that is the fact that Lilly had 12 hired him as a consultant on a registration 13 question in another country? 14 A. That point doesn't strike me 15 as terribly important. 16 Q. All right. Well, then, what's 17 important about it is whether or not it's of an 18 accurate scientific conclusion? 19 A. Correct. 20 Q. And if it is accurate, it 21 would need to be forwarded and action be taken 22 immediately, correct? 23 A. Very rapidly. The term 24 immediate, I think, took on a regulatory Page 193 1 definition, but very rapidly. 2 Q. As soon as possible, would 3 that be a better phrase? 4 A. Yes. 5 Q. But if it's something that 6 Lilly disagrees with for what they think is a 7 good scientific basis, then that's still 8 something that probably should be reported to the 9 United States Food and Drug Administration, just 10 not so quickly, correct? 11 A. Yes. 12 Q. And how long would you have 13 taken as a regulatory scientist, had you seen 14 this report and had it been a matter that you 15 disagreed with for scientific reason, before you 16 would have submitted it to the United States Food 17 and Drug Administration? 18 A. I'm looking at the date with 19 respect to the New Drug Application. I might 20 submit it at the time of the next annual report 21 to the IND, for example. 22 Q. All right. Does the fact that 23 this drug is under investigation by the United 24 States Food and Drug Administration at this very Page 194 1 time that this consultant purportedly makes this 2 statement concerning the high incidence of 3 suicide attempts on the Prozac group make any 4 difference as to whether or not the U.S. FDA 5 should see it? Do you follow what I'm saying? 6 A. I think part of your premise 7 was that FDA, as is under active investigation? 8 Q. Yes, in April of 1985 -- 9 A. Wait, I'm sorry, I'm sorry, 10 I'm confusing dates. So this is well after 11 submission of the New Drug Application -- 12 Q. Well, before it was approved. 13 A. -- but before it was approved. 14 I'm not sure now when I would have submitted it, 15 given all of the assumptions that we've made. 16 Q. But you follow my point, this 17 is a product that's under investigation in 18 Germany, and it's a product that's under 19 investigation in the United States, both 20 concurrently. 21 A. If you forgive my quibbling, I 22 think FDA would call it under review. 23 Q. Under review, okay. I guess 24 the BGA in Germany was reviewing it at the same Page 195 1 time the United States Food and Drug 2 Administration was reviewing it, correct? 3 A. Yes. 4 Q. And they were reviewing this 5 data for safety, both governments were, were they 6 not? 7 A. And efficacy. 8 Q. And efficacy. But safety for 9 sure, right? 10 A. Yes. 11 Q. And this summary of this 12 twenty-one page opinion is in fact broken down 13 into efficacy and safety, correct? 14 A. Yes. 15 Q. And the issue with respect to 16 suicidality is in the safety portion of the 17 section, correct -- 18 A. Yes. 19 Q. -- of the summary? 20 A. Yes. 21 Q. Had you ever seen anybody who 22 had expressed an opinion that it is of importance 23 to determine certain types of patients who will 24 better respond to fluoxetine than to imipramine Page 196 1 so that a higher risk might be acceptable 2 expressed? Do you see where I'm reading? 3 A. Yes. The goal within 4 psychopharmacology, and this applies to 5 fluoxetine as it has applied to other agents back 6 for close to thirty years, to my personal 7 knowledge, has been to identify specific patient 8 or fairly specific patient populations who might 9 best respond to Drug A versus Drug B versus Drug 10 C, not just in the antidepressant field, but 11 antipsychotic and so forth. And that goal has 12 been avidly pursued for many years to my personal 13 knowledge, and probably still is. 14 Q. You think that's an admirable 15 goal? 16 A. I think that's an admirable 17 goal. And to the best of my knowledge, it's 18 never been achieved. I recall one eminent expert 19 who referred to such endeavors as seeking the red 20 headed patients with red headed guitar playing 21 Swedish grandmother syndrome as his way of 22 ridiculing, if you will, the unsuccessful 23 efforts. 24 Q. Well, but this doctor, this Page 197 1 Doctor Herrmann, is talking about if you get 2 people that will respond better to Prozac, then 3 you will have I assume a lower incidence of a 4 risk that is unacceptable, is that right, is that 5 what he's saying on the bottom of page two under 6 benefit risk ratio? 7 A. Let me reread it if I may. 8 Q. Sure. 9 A. I'm sorry, would you repeat 10 the question, please? 11 Q. Well, isn't he saying here 12 that in order to encompass this higher risk, that 13 is of suicidality, we better find us some 14 patients that will respond better to Prozac than 15 to imipramine -- or find us some patients that 16 will respond better to Prozac than imipramine so 17 that we can make this higher risk acceptable, 18 isn't that what he's saying? 19 A. I guess so, I don't -- 20 Q. Is that a reasonable 21 interpretation of what we see written here? 22 A. I think so. 23 Q. Again, wouldn't it be better 24 to have that report to know specifically whether Page 198 1 he gave any detail in connection with this? 2 A. Yes. And, of course, I don't 3 accept the premise that I think he's tucked in 4 there. 5 Q. Well -- 6 A. Based on something, I don't 7 know what. Doctor Herrmann had apparently 8 concluded, as we've said elsewhere, that the risk 9 of suicide with fluoxetine is greater than with 10 imipramine. 11 Q. That's a pretty astounding 12 statement to see, isn't it, Doctor Dobbs? 13 A. Yes, and if I accepted it, I 14 might stop a few patients from Prozac tonight, 15 but I don't accept it. 16 Q. But you don't know whether to 17 accept it or not, do you, Doctor Dobbs, because 18 you don't even have the benefit of what this 19 man's twenty-one page opinion is, do you? 20 A. Correct, I don't. 21 Q. You would be in a better 22 position to know whether to accept it or reject 23 it -- you would be in a better position to know 24 whether to accept it or reject it if you could Page 199 1 see the full report, correct? 2 A. Somewhat. However, I don't 3 have that bit of data, but at this point, while I 4 have long left the field, I still have respect 5 both for my former -- both of my former 6 employers, Eli Lilly and Company and the Food and 7 Drug Administration. If this report were true, 8 somehow it is my firm conviction that Lilly 9 and/or FDA, and I believe both, would have taken 10 suitable action. 11 Q. What if the FDA didn't know 12 about it, Doctor Dobbs? 13 A. They may never have known of 14 this, whatever it was, but there are indeed many 15 other studies and many other sources of 16 information. 17 Q. Doesn't the FDA want the 18 benefit of all studies and all sources of 19 information so that they can make their 20 determination concerning these issues, Doctor 21 Dobbs? 22 A. Yes. 23 Q. That's the purpose of 24 providing that information? Page 200 1 MR. FREEMAN: You've got a good 2 answer, now quit. 3 (DISCUSSION OFF THE RECORD.) 4 Q. Doctor Dobbs, the issue of 5 concomitant medication has come up in connection 6 with the clinical trials that were conducted with 7 respect to Prozac. 8 A. Yes. 9 (DISCUSSION OFF THE RECORD.) 10 Q. I'm going to give you an 11 unstapled document that we'll give you just as 12 soon as the court reporter marks it. 13 (PLAINTIFFS' EXHIBIT NO. 10 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 Q. We may be able to shorten 17 this, Doctor Dobbs, without having you go through 18 the entire document. Exhibit 10 is a document 19 that apparently is signed by you. Is that your 20 signature? 21 A. Yes. 22 Q. Dated December 17, 1984, where 23 you transmit a table containing concomitant 24 medications administered during the Prozac Page 201 1 clinical trial, is that right? 2 A. Yes. 3 Q. Do you recall doing this? 4 A. I can very, very vaguely, I 5 remember Doctor Lee -- I vaguely remember the 6 issue. 7 Q. Do you remember why the issue 8 came up? 9 A. I believe in some of our 10 earlier studies that had been designed and at 11 least in part conducted prior to my joining 12 Lilly, the protocols allowed a wide variety of 13 CNS active medication, and the major difficulty 14 is that these interfere with the analysis of both 15 safety and efficacy, actually. Ideally patients 16 in clinical trials would be completely healthy, 17 except for whatever disease was under study, and 18 would not ingest a single aspirin. That, of 19 course, is not real. But this -- I think I share 20 the opinion, frankly, of Doctor Lee in the 21 earlier studies that we had. 22 Q. Too many people on too much 23 concomitant medication? 24 A. Yes. Page 202 1 Q. Too many psychotropic and 2 concomitant medication, correct? 3 A. Yes, and even -- well, some of 4 the ones mentioned under other CNS effect 5 medications, Demerol, for example, would confound 6 the results somewhat. 7 Q. Demerol would blow it all to 8 hell, wouldn't it, Doctor Dobbs. I mean Demerol 9 puts me on the ceiling. 10 A. I was attempting -- it puts me 11 on the floor, and I throw up a lot with the one 12 time I took it. 13 Q. Me too. I got kidney stones, 14 I have to take Demerol for kidney stones. 15 A. My point is, if the patient 16 had been somewhat agitated and gets Demerol, 17 goodness knows why, does that look like 18 improvement, you know, there could be 19 interference from any -- from a number of other 20 drugs. 21 Q. Would these patients that are 22 listed, and these patients were put on these 23 concomitant psychotropic medications that might 24 interfere with an accurate reading of the safety Page 203 1 and efficacy of Prozac, would they have been put 2 on this medication for treatment emergent 3 symptoms or would these have been symptoms that 4 they had experienced prior to and were taking 5 these medications at the time of entry into the 6 clinical trials? 7 A. It might have been either. 8 Q. Let me see if I can shorten my 9 question. 10 A. Okay. 11 Q. Were patients -- if I'm taking 12 benzodiazepine and I'm depressed and I fit all 13 the criteria, will I be allowed on the clinical 14 trial? 15 A. That would depend on the 16 wording in the protocol. The question then 17 becomes what should the protocol say. 18 Q. All right. Do you have a 19 recollection? 20 A. My recollection is that some 21 of the studies, as I said, that had been started 22 earlier, and probably before I was there, allowed -- 23 well, this says allowed psychotropics, including 24 benzodiazepines and chloral hydrate, and -- so Page 204 1 two patients in this group get one milligram of 2 one of them, and five patients over here get ten 3 milligrams of another one for three nights, and 4 it simply fouls it up. 5 Q. It's bad? 6 A. It's bad, it's scientifically 7 bad. 8 Q. But it was allowed on the 9 Prozac clinical trials? 10 A. As I've already acknowledged, 11 I advised within Lilly that that -- before Doctor 12 Lee did, that that practice ceased. 13 Q. But it didn't, did it? 14 A. We -- I believe we arrived at 15 something that was considerably cleaner. As I 16 said, the ideal in this situation is not 17 attainable, and the -- what might be attainable 18 is to specify one drug, you know, if a patient 19 can't sleep, use this dose of this drug, and at 20 least you can count that. 21 Q. But none of that was ever 22 done, as far as I can tell, none of the protocols 23 were changed to reduce the amount of concomitant 24 medications? Page 205 1 A. Then my memory is failing me 2 with great rapidity because I thought we did. 3 Q. Okay. In other words, there 4 might have been a change in practice. And I 5 don't want to mislead you, your recollection may 6 be better than mine, you were there, I wasn't. 7 A. But you've seen protocols much 8 more recently than I have. 9 Q. Okay. It might have been that 10 you might have given instructions to the 11 investigators to limit that, but never changed 12 the protocol. Or which was it, is it your 13 recollection -- if it is your recollection that 14 you actually changed -- 15 A. I thought we tightened 16 protocols in that regard. 17 Q. And that would have been in 18 when? 19 A. Well, I started Lilly in 20 November of 1981, and recognized this issue 21 shortly thereafter and advised against it and 22 discussed it with Doctor Christensen, and I 23 thought we made some changes in future protocols. 24 But I could be totally wrong. Page 206 1 Q. Did you really see any change 2 in practice, Doctor Dobbs? 3 A. I thought we had. If you were 4 to show me successive protocols that were not 5 different -- 6 Q. Well, this is dated December 7 17, 1984, and it's got a lot of people on 8 concomitant medications. This is dated after -- 9 A. CNS active medications? 10 Q. Yes. I mean don't you agree 11 this is a lot of CNS active medications for a CNS 12 drug such as Prozac? 13 A. Are we talking about the same 14 document? 15 Q. See, there's a tabulation 16 behind this that lists specifically drugs that 17 were given to patients, and everything up through 18 1984, December, '84, and it looks like a lot of 19 medication. 20 A. I was thinking that we had 21 narrowed things down to chloral hydrate. This is 22 protocol nineteen, and I don't remember when that 23 was initiated, of course. 24 Q. Yes, but it looks like we go Page 207 1 through protocol nineteen through thirty-five. 2 MR. FREEMAN: Well, it says what it 3 says, if she doesn't recall, she doesn't recall. 4 A. Obviously my recollection is 5 faulty. 6 Q. My point is simply, and you're 7 free to look at this, but my point is simply, 8 Doctor Dobbs, that it appears to me that you may 9 have been under the impression that the procedure 10 was changed where there weren't as many people 11 receiving concomitant psychotropic medications, 12 but it doesn't look like it in looking at these 13 tables that were dated as of December 17, 1984. 14 A. I have to agree with you. 15 Q. Doctor, you said earlier that -- 16 and I wrote a lot of quotes here -- that you 17 can't determine, in connection with causal 18 relationship, between a particular event and a 19 drug. You say, quote, by and large, one can't 20 establish whether or not there is a causal 21 relationship, and you say it's speculative 22 regarding a causal relationship and then you talk 23 about reviewing matters on an individual, 24 case-by-case basis, correct? Were those accurate Page 208 1 quotes? 2 MR. FREEMAN: She was talking about, I 3 believe, with respect to one single patient, not 4 groups. 5 MR. SMITH: Yes. 6 A. Uh-huh. 7 Q. You say the reality is that 8 one cannot establish causality in any -- on many 9 situations, is that right? 10 A. Yes. 11 Q. Does that mean conversely that 12 if you're taking these by an individual 13 case-by-case basis, that you can say with 14 particular -- with one particular individual that 15 the medication may have caused a particular 16 reaction or event? 17 A. I think I illustrated that 18 when I was talking about the incidence of nausea. 19 Q. All right. 20 A. Patient has no prior history 21 of gastrointestinal disease, have no symptoms of 22 a, quote, GI flu, other than nausea, experiences 23 nausea with fluoxetine or Drug X, drug is 24 stopped, nausea goes away. We've gone through Page 209 1 that routine. Yes, my evaluation of the 2 probability would increase so that it was 3 approaching a hundred percent if I were to go 4 through that exercise. 5 Q. Did you say you could go 6 through the same exercise with suicidality? 7 A. No, I did not. 8 Q. Why is it that you believe you 9 cannot do that? 10 A. If I had the slightest 11 suspicion that Drug X -- let's get away from 12 fluoxetine just for the moment so that I can talk 13 in generalities. I'm treating a patient, the 14 patient is being treated with Drug X, the 15 patient, for the first time, to my knowledge, 16 expresses suicidal thoughts that I take 17 seriously. 18 Q. As valid. 19 A. Yes. I doubt seriously that 20 the drug that he or she is taking is causing 21 suicide because I know that that happens with 22 depressed -- depressive illness. 23 Q. All right. 24 A. But hypothetically, I think Page 210 1 hey, that is a possibility because there was some 2 statement in the literature, for whatever reason. 3 Even if I regard that as highly, highly unlikely, 4 I'm not going to treat the patient like a guinea 5 pig, I'm going to treat the patient as well as I 6 know how, and if I take the risk of suicide 7 seriously and if it is at all feasible, I'll 8 hospitalize the patient. 9 Q. All right. 10 A. Because the patient's welfare 11 is a primary concern to me, naturally, and 12 deciding did Drug X cause this is not of any 13 importance and certainly not worth a risk to that 14 particular patient. 15 Q. I understand that in that 16 particular patient. But in deciding whether or 17 not to prescribe the medication, if the drug 18 produced a risk that it might cause some people 19 to become suicidality, wouldn't -- to become 20 suicidal, wouldn't you want, as a physician, to 21 know that about that drug? 22 A. I would dearly love to be able 23 to look at a patient or run a lab test or read a 24 book and find out some of the things that you're Page 211 1 talking about, but to suggest that I would 2 conduct this, to me, pointless exercise with my 3 individual patient would contribute to general 4 knowledge for me and my colleagues henceforth, is 5 frankly, I'm sorry, an absurdity, because it 6 wouldn't. 7 Q. And I'm not suggesting that. 8 And maybe we're not communicating. 9 A. We're probably not. 10 Q. If Eli Lilly and Company, as 11 the manufacturer of the drug, had evidence that 12 the drug might produce suicidality or suicidal 13 tendencies in some individuals, wouldn't you want 14 Lilly to make that risk available to the 15 physicians so they could make that determination 16 in prescribing the drug? 17 A. If your premise -- if I 18 accepted your premise, that Lilly would be 19 obligated to inform the Food and Drug 20 Administration, and B, if all of those things 21 applied and the risk were definitely higher, I 22 don't think Lilly would have much reason to worry 23 about notifying physicians in the United States 24 because I don't think the drug would be there. Page 212 1 Q. All right. Did you know that 2 Germany has prescribing information that suggests 3 that Prozac should be used with concomitant 4 medications such as tranquilizers in patients 5 exhibiting risk factors for suicide? 6 MR. FREEMAN: How it may be used. 7 A. Did I know that that's the 8 case, no, I did not. 9 Q. Did you know that that was the 10 only way that Lilly was allowed to market Prozac 11 in Germany, was to have that type of information 12 in the package literature? 13 MR. FREEMAN: There's no evidence of 14 that. 15 Q. Take my word for it. 16 MR. FREEMAN: Don't do that, because 17 that ain't so. 18 A. I'm sorry. 19 Q. Did you know -- let me 20 withdraw that question. Did you know that Lilly 21 had to withdraw their application for marketing 22 Prozac in Germany? 23 A. No. 24 Q. You didn't know that? Page 213 1 A. No. 2 Q. And did you know that one of 3 the reasons they had to withdraw their 4 application was because the BGA, the German 5 equivalent to the FDA, felt like it presented a 6 risk for suicidal patients? 7 MR. FREEMAN: Let's wait until the 8 proof is in on that because there's no evidence 9 of it at the present time. 10 MR. SMITH: I'm entitled to get an 11 answer. If I don't get the proof, then I don't 12 get to read it. 13 A. This may or may not be a 14 responsive answer. I've known FDA officials to 15 make rather silly mistakes. 16 Q. You're not suggesting that 17 this is a silly mistake on the part of the -- 18 A. I don't know what their basis 19 for making it was, but I'm also saying that 20 regulatory officials in the United States and 21 elsewhere are far from infallible. 22 Q. Why, I agree. Of course the 23 United States FDA could have made the mistake and 24 the BGA could be correct, too. Page 214 1 MR. FREEMAN: They both approved the 2 drug, come on. 3 A. Okay. I know wherein my 4 higher opinion rests. 5 Q. All right. Do you know Doctor 6 Paul Leber? 7 A. Is this on the record? 8 MR. FREEMAN: Yes. 9 A. Yes. 10 Q. What is your opinion of Doctor 11 Paul Leber? 12 A. Not high. 13 Q. And why is that? 14 A. I'm so utterly turned off by 15 Doctor Leber's personality, that it's a little 16 difficult for me to assess his competence, which 17 in any event is not in the area of psychiatry. 18 Q. He's the head of the 19 neuropsychopharmacological drug division, isn't 20 he? 21 A. A, that isn't the title of it, 22 and B, yes, I suppose he still is as far as I 23 know. 24 Q. Isn't he the head of the Page 215 1 division at the Food and Drug Administration that 2 approves psychiatric compounds such as Prozac? 3 A. That's true. 4 Q. And he's not competent as a 5 psychiatrist, in your opinion? 6 A. He's not competent or 7 incompetent as a psychiatrist, he isn't a 8 psychiatrist. 9 Q. Do you feel he's competent to 10 make judgments with respect to whether or not a 11 psychotropic medication is safe and efficacious 12 for use by the public? 13 A. Most of the judgments 14 expressed by Doctor Leber are not his judgments, 15 he's expressing the judgments of various 16 reviewers. 17 Q. I'm asking you about his 18 judgment. 19 A. I beg your pardon? 20 Q. I'm asking you about his 21 judgment. 22 MR. FREEMAN: She just answered that. 23 A. I've really had little 24 face-to-face contact with Doctor Leber. As I Page 216 1 said, I find his personality so irritating that 2 it's hard to get beyond that. 3 Q. What is it -- 4 A. I don't know, I can't tell 5 what is his personal opinion and what is being 6 expressed. 7 Q. What if he expressed an 8 opinion such as we should put a cap on the number 9 of events in connection with reports of suicide 10 and Prozac? 11 MR. FREEMAN: Now, that's taken 12 completely out of context, so let's don't get 13 into something that's totally -- 14 A. I have no earthly idea of what 15 you're talking about. 16 Q. I understand that, I didn't 17 bring that document with me. 18 A. Wonderful. 19 Q. But you don't have a high 20 opinion of Doctor Leber? 21 A. No, I do not. 22 Q. You can leave it at that. 23 A. As a person. 24 Q. How about Doctor Tom Laughren? Page 217 1 A. I'm sorry? 2 Q. Doctor Thomas Laughren? 3 A. Offhand, that name means 4 nothing to me. 5 Q. How about Doctor Bob Temple, 6 Robert Temple? 7 A. I have met Doctor Temple. As 8 I recall, he came to FDA after I left. I've seen 9 him in meetings, had one or two brief 10 conversations with him. He seems bright, he 11 seems -- or seemed, I have no reason to question 12 his competency. 13 Q. Did you work with Doctor 14 Leber? 15 A. No. 16 Q. Would he have been -- what has 17 been your association with Doctor Leber, just 18 through your -- 19 A. Occasional meetings at FDA, 20 correspondence -- and correspondence. 21 MR. SMITH: Thank you, Doctor Dobbs, 22 that's all I have. 23 MR. FREEMAN: No questions. 24 (THE WITNESS WAS EXCUSED.) Page 218 1 COMMONWEALTH OF KENTUCKY ) : ss 2 COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 Dr. Dorothy Dobbs 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 28TH DAY OF 19 JULY, 1994. 20 MY COMMISSION EXPIRES MARCH 10, 1994. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 219 1 2 3 E R R A T A S H E E T 4 5 STATE OF ) : SS 6 COUNTY OF ) 7 8 I, DR. DOROTHY DOBBS, THE UNDERSIGNED 9 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 10 OF MY DEPOSITION AND WITH THE CHANGES NOTED 11 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 12 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 13 JULY 11, 1994 AT THE TIME AND PLACE STATED 14 THEREIN. 15 PAGE NO. LINE NO. CHANGE REASON Page 220 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. DOROTHY DOBBS 10 SWORN TO AND SUBSCRIBED BEFORE ME THIS 11 _____ DAY OF __________, 1994. 12 _____________________________ NOTARY PUBLIC, STATE OF 13 AT LARGE Page 221 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Page 222 1 DIRECT EXAMINATIONBY MS. ZETTLER:..................1 2 EXAMINATIONBY MR. SMITH:.........................100 3 COMMONWEALTH.....................................172 4 (PLAINTIFFS' EXHIBIT NO. 1........................46 5 PLAINTIFFS' EXHIBIT NO. 2.........................53 6 PLAINTIFFS' EXHIBIT NO. 3.........................57 7 PLAINTIFFS' EXHIBIT NO. 4.........................62 8 PLAINTIFFS' EXHIBIT NO. 5.........................69 9 PLAINTIFFS' EXHIBIT NO. 6.........................88 10 PLAINTIFFS' EXHIBIT NO. 7.........................93 11 PLAINTIFFS' EXHIBIT NO. 8.........................97 12 PLAINTIFFS' EXHIBIT NO. 9........................141 13 PLAINTIFFS' EXHIBIT NO. 10.......................157 14 15 16 17 18 Page 223 1 DIRECT EXAMINATIONBY MS. ZETTLER:..................1 2 EXAMINATIONBY MR. SMITH:.........................101 3 COMMONWEALTH.....................................173 4 (PLAINTIFFS' EXHIBIT NO. 1........................47 5 PLAINTIFFS' EXHIBIT NO. 2.........................53 6 PLAINTIFFS' EXHIBIT NO. 3.........................58 7 PLAINTIFFS' EXHIBIT NO. 4.........................63 8 PLAINTIFFS' EXHIBIT NO. 5.........................70 9 PLAINTIFFS' EXHIBIT NO. 6.........................89 10 PLAINTIFFS' EXHIBIT NO. 7.........................94 11 PLAINTIFFS' EXHIBIT NO. 8.........................97 12 PLAINTIFFS' EXHIBIT NO. 9........................142 13 PLAINTIFFS' EXHIBIT NO. 10.......................158 14 15 16 17 18 Page 224 1 DIRECT EXAMINATIONBY MS. ZETTLER:..................1 2 EXAMINATIONBY MR. SMITH:.........................101 3 COMMONWEALTH.....................................172 4 (PLAINTIFFS' EXHIBIT NO. 1........................46 5 PLAINTIFFS' EXHIBIT NO. 2.........................53 6 PLAINTIFFS' EXHIBIT NO. 3.........................58 7 PLAINTIFFS' EXHIBIT NO. 4.........................63 8 PLAINTIFFS' EXHIBIT NO. 5.........................70 9 PLAINTIFFS' EXHIBIT NO. 6.........................89 10 PLAINTIFFS' EXHIBIT NO. 7.........................94 11 PLAINTIFFS' EXHIBIT NO. 8.........................97 12 PLAINTIFFS' EXHIBIT NO. 9........................141 13 PLAINTIFFS' EXHIBIT NO. 10.......................157 14 15 16 17 18 Page 225 1 DIRECT EXAMINATIONBY MS. ZETTLER:.................12 2 EXAMINATIONBY MR. SMITH:.........................133 3 COMMONWEALTH.....................................219 4 (PLAINTIFFS' EXHIBIT NO. 1........................67 5 PLAINTIFFS' EXHIBIT NO. 2.........................75 6 PLAINTIFFS' EXHIBIT NO. 3.........................80 7 PLAINTIFFS' EXHIBIT NO. 4.........................86 8 PLAINTIFFS' EXHIBIT NO. 5.........................96 9 PLAINTIFFS' EXHIBIT NO. 6........................118 10 PLAINTIFFS' EXHIBIT NO. 7........................125 11 PLAINTIFFS' EXHIBIT NO. 8........................129 12 PLAINTIFFS' EXHIBIT NO. 9........................183 13 PLAINTIFFS' EXHIBIT NO. 10.......................201 14 15 16 17 18 Page 226