1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT 2 DIVISION ONE (1) 3 *-*-*-*-* 4 JOYCE FENTRESS, ET AL. PLAINTIFFS 5 6 VS. DEPOSITION FOR PLAINTIFFS 7 8 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 9 10 11 *-*-*-*-* 12 13 14 DEPONENT: W. LEIGH THOMPSON, MD 15 16 DATE: JULY 20, 21 AND 22, 1994 17 18 REPORTER: MARY KATHLEEN NOLD 19 20 *-*-*-*-* 21 22 KENTUCKIANA REPORTERS 730 WEST MAIN STREET, SUITE 250 23 LOUISVILLE, KENTUCKY 40202 (502) 589-2273 24 1 1 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 2 INDIANAPOLIS DIVISION 3 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 4 Litigation ) 5 *-*-*-*-* 6 NO. 91-02496-A 7 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 8 V. ) DALLAS COUNTY, TEXAS ) 9 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 10 *-*-*-*-* 11 NO. 92-14775-E 12 RICHARD HAROLD CROSSETT, JR., ) IN THE 13 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT,) COURT OF 14 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 15 JOCQUETTA ANN CROSSETT, DECEASED ) ) 16 V. ) DALLAS COUNTY, ) TEXAS 17 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 18 PSYCHIATRIC COMPANY, INC. ) D/B/A HCA WILLOW PARK ) 101st JUDICIAL 19 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D ) 20 *-*-*-*-* 21 22 23 24 2 1 NO. A-921,405-C 2 MARIA GUADALUPE REVES ) IN THE INDIVIDUALLY AND AS NEXT ) DISTRICT COURT 3 FRIEND OF GRANT JULIAN REVES ) OF A MINOR CHILD, AND ON BEHALF ) 4 OF THE ESTATE OF CHRISTIAN ) MARIE REVES, DECEASED ) 5 ) V. ) ORANGE COUNTY, 6 ) TEXAS ELI LILLY & COMPANY, DISTA ) 7 PRODUCTS COMPANY, RAVIKUMAR ) KANNEGANTI, M.D., HOSPITAL ) 8 CORPORATION OF AMERICA, A ) TENNESSEE CORPORATION, HEALTH ) 9 SERVICES ACQUISITION CORP., ) A DELAWARE CORPORATION, ) 10 HCA PSYCHIATRIC COMPANY, A ) DELAWARE CORPORATION, TEXAS ) 11 PSYCHIATRIC CO., INC., A/K/A ) AND/OR D/B/A HCA BEAUMONT ) 12 NEUROLOGICAL HOSPITAL, AND HCA) HEALTH SERVICES OF TEXAS, INC.) 128TH JUDICIAL 13 A/K/A AND/OR BEAUMONT ) DISTRICT NEUROLOGICAL HOSPITAL ) 14 *-*-*-*-* 15 16 17 18 19 20 21 22 23 24 3 1 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS COUNTY DEPARTMENT - LAW DIVISION 2 RENATO DI SILVESTRO, Individually) 3 and as Special Administrator of ) the Estate of JOHN DI SILVESTRO, ) 4 Deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91-l-7881 ) 7 ROBERT L. NELSON, et al., ) ) 8 Defendants, ) ) 9 GEORGE MELNICK, M.D., and PETER ) FINK, M.D. ) 10 ) RESPONDENTS IN DISCOVERY.) 11 *-*-*-*-* 12 SUPERIOR COURT OF THE STATE OF CALIFORNIA 13 FOR THE COUNTY OF LOS ANGELES 14 DR. MARIUS SAINES, etc., et al., ) Case No.: ) SC 008331 15 ) Plaintiffs, ) 16 ) vs. ) 17 ) ELI LILLY & COMPANY, a corporation;) 18 DISTA PRODUCTS COMPANY, a Division ) of Eli Lilly & Company; and DOBS 1-) 19 100, Inclusive, ) ) 20 Defendants. ) ___________________________________) 21 *-*-*-*-* 22 23 24 4 1 NO. 93-8792-D 2 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF 3 INDIVIDUALLY AND AS SURVIVORS ) AND STATUTORY BENEFICIARIES ) 4 OF MAY YUN KUNG, DECEASED ) ) 5 VS. ) DALLAS, COUNTY ) TEXAS 6 ELI LILLY AND COMPANY, DISTA ) PRODUCTS COMPANY, AND MONIQUE ) 7 KUNKLE, PH.D. ) 8 *-*-*-*-* 9 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS CIVIL COURT DEPARTMENT 10 EUGENE HUSLIG, AS ADMINISTRATOR ) 11 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 12 HUSLIG, DECEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 13 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 14 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 15 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 16 ) 94 C 192 PLAINTIFFS, ) 17 ) COURT NO. 7 VS. ) CHAPTER 60 18 ) MARY L. BILLINGSLEY, EXECUTOR OF ) 19 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 20 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 21 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 22 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 23 ) DEFENDANTS. ) 24 5 1 CAUSE NO. 93-04911-A 2 LINDA JILL WELCH, CARLINDA WELCH REX, CONNAN ROSS WELCH 3 AND CHAD MICHAEL WELCH, INDIVIDUALLY AND AS SURVIVORS 4 AND STATUTORY BENEFICIARIES OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 5 V. 6 ELI LILLY AND COMPANY, DISTA 7 PRODUCTS COMPANY, NOE NEAVES, M.D., AND MINITH-MEIER 8 CLINIC, P.A. DEFENDANTS 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 6 1 I N D E X 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 7 1 THE FOLLOWING DEPOSITION 2 OF W. LEIGH THOMPSON, MD, WAS TAKEN AT THE OFFICES 3 OF BAKER & DANIELS, 300 NORTH MERIDIAN STREET, 4 SUITE 270, INDIANAPOLIS, INDIANA, 46204, ON JULY 5 20, 21 AND 22, 1994; SAID DEPOSITION TAKEN 6 PURSUANT TO NOTICE IN ACCORDANCE WITH THE RULES OF 7 CIVIL PROCEDURE. 8 *-*-*-*-* 9 A P P E A R A N C E S 10 11 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 12 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 13 14 15 PAUL SMITH COUNSEL FOR PLAINTIFFS 16 745 CAMPBELL CENTER 2 8115 NORTH CENTRAL EXPRESSWAY 17 DALLAS, TEXAS 75206 18 WILLIAM J. DOWNEY, III FOR PLAINTIFF SAINES 19 MCCARTER & ENGLISH 12100 WILSHIRE BOULEVARD, SUITE 650 20 LOS ANGELES, CALIFORNIA 90025 21 JOE FREEMAN LAWRENCE J. MEYERS 22 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 23 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 24 ATLANTA, GEORGIA 30308-3243 8 1 APPEARANCES (CONTINUED) 2 JOHN BRENNAN COUNSEL FOR ELI LILLY AND COMPANY 3 FOUR GATEWAY CENTER 100 MULBEWRRY STREET 4 NEWARK, NEW JERSEY 07102-4096 5 MARY HUFF ELI LILLY AND COMPANY 6 LILLY CORPORATE CENTER INDIANAPOLIS, INDIANA 46285 7 8 9 BEATRICE M. SMITH COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 10 FRIEND & ASSOCIATES LLP 1301 MCKINNEY, #2900 11 HOUSTON, TEXAS 77010 12 13 BARTON BROWN COUNSEL FOR DOCTOR BILLINGSLEY 14 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 10111 WEST 8TH STREET 15 PO BOX 12290 OVERLAND PARK, KANSAS 66282 16 17 18 KATHERINE L. LAWS COUNSEL FOR DOCTORS WITSCHY AND KANNEGANTI 19 BAILEY & WILLIAMS 3500 NCNB PLAZA 20 901 MAIN STREET DALLAS, TEXAS 75202-3714 21 22 23 24 9 1 MR. FREEMAN: Let me just 2 state at this time a little brief stipulation. 3 This is the deposition of Leigh Thompson taken on 4 behalf of the plaintiffs for purposes of discovery 5 and use at the trial on any of the cases 6 heretofore recited. The deposition of Doctor 7 Thompson is taken by agreement of counsel and by 8 notice in the offices of Baker and Daniel in 9 Indianapolis. 10 Objection will be made at 11 this time as to any leading questions that Doctor 12 Thompson's own counsel may put to him or any 13 objection that any lawyer may have to the 14 witness's response to the questions propounded. 15 All other objections will be reserved until the 16 time of court hearing. 17 * * * * * 18 W. LEIGH THOMPSON, called 19 by Plaintiffs, after having been first duly sworn, 20 was examined and deposed as follows: 21 22 DIRECT EXAMINATION 23 BY MR. SMITH: 24 Q Would you state your name 10 1 please, sir? 2 A Wilmer, W-I-L-M-E-R, 3 Leigh, L-E-I-G-H, Thompson, T-H-O-M-P-S-O-N, and 4 I'm often referred to as Junior, although my 5 father is deceased. 6 Q How old a man are you, 7 Doctor Thompson? 8 A I'm fifty-six years old. 9 Q And where do you live? 10 A I live in Carmel, 11 Indiana. 12 Q Does anybody live with 13 you there in Carmel, Indiana? 14 A My wife does. 15 Q Do you have children, 16 sir? 17 A Yes, sir, I have one 18 daughter. 19 Q Does she live in your 20 home or is she -- 21 A No. 22 Q -- away from home? 23 A She lives in California. 24 Q Does your wife work 11 1 outside the home? 2 A Only as a volunteer. 3 Q You are a medical doctor, 4 are you not, sir? 5 A Yes, sir. 6 Q And when did you receive 7 your MD degree? 8 A 1965. 9 Q From what institution, 10 sir? 11 A The Johns Hopkins 12 University. 13 Q Where did you do your 14 undergraduate work? 15 A I went to the University 16 of Chicago, the University of South Carolina, and 17 I graduated from the College of Charleston in 18 Charleston, South Carolina. 19 Q And when did you 20 graduate? 21 A I completed my course 22 work in 1957, the degree was awarded in 1958. 23 Q How come? 24 A Because they only had one 12 1 commencement per year and I completed my course 2 work at the end of the summer. 3 Q All right. What was your 4 degree in? 5 A It was a Bachelor of 6 Science Degree with a major in biology. 7 Q Any other postgraduate 8 work other than your medical degree? 9 A Yes, sir. 10 Q Tell me about that, sir. 11 A I attended the Medical 12 College, at that time, now Medical University of 13 South Carolina and received a Master of Science 14 Degree in Pharmacology, followed by a Ph.D. in 15 Pharmacology. 16 Q And when did you receive 17 those degrees, sir? 18 A In 1960 and 1963. 19 Q You got your master's in 20 1960 and your Ph.D. in 1963? 21 A Yes, sir. 22 Q And your medical degree 23 in 1965? 24 A That's correct. 13 1 Q Well, did some of the 2 work that you did in your Ph.D. apply toward your 3 MD degree? 4 A No, sir, I took two years 5 of medical school as a medical student at the 6 Medical University of South Carolina, then the 7 College, before going to Johns Hopkins, which I 8 entered as a junior medical student. 9 Q All right. Did you 10 receive your Ph.D. while you were also a medical 11 student? 12 A No, sir, I was an 13 undergraduate student. I went to graduate school 14 for two years, medical school for two years, back 15 to graduate school for one year. 16 Q When did you develop an 17 interest in pharmacology? 18 A Well, I would say in 19 1958, when I first went to graduate school, 20 because the -- my mentor was chairman of the 21 Department of Pharmacology at the Medical College 22 of South Carolina. 23 Q What about pharmacology 24 particularly drew your interest, anything in 14 1 particular? 2 A Well, I was very much 3 interested in helping patients, and I thought the 4 kinds of research done in pharmacology had direct 5 applicability, was a highly practical form of 6 research in terms of helping people. 7 Q Did you intend at that 8 time to become a medical doctor, as early as 1958? 9 A I'm not sure in 1958 that 10 my exact career plans were clear, but they 11 certainly became clear after I had spent some time 12 in graduate school and understood the differences 13 between a Ph.D. and an MD and what each degree 14 would prepare me for. 15 Q Did you -- when you 16 started your MD career or course work, did you 17 intend to become a practicing physician or was 18 your interest in research? 19 A Well, my interest was 20 both in being able to care for patients as well as 21 in doing research and teaching. So, I think from 22 the time I began to understand what I wanted to do 23 with my life in graduate school, I wanted to do 24 all three of those things. 15 1 Q And have you participated 2 in any patient care, Doctor Thompson? 3 A Yes, sir. 4 Q In a private practice 5 setting? 6 A No, sir, except as a 7 member of a faculty in which I had private 8 patients, but in whom the billing for those 9 patients went to a faculty or university 10 consortium rather than to me personally. 11 Q But you've never been a 12 practicing physician holding yourself out as being 13 in the business of seeing private patients for 14 care on a per office visit type basis where you 15 received money for those office visits that went 16 to you, as most doctors in the country? 17 A Well, that's a 18 complicated answer. Yes, I did see outpatients, 19 and yes, they were billed, and yes, those fees 20 were collected by the University, but part of 21 those fees may have contributed to my salary and 22 bonuses from the University, but I most certainly 23 was seeing both inpatients in my critical care 24 units, as well as outpatients. 16 1 Q But you've not been a 2 physician treating patients and charging those 3 patients as your source of livelihood? 4 A Well, again, the source 5 of income from both universities by whom I was 6 employed was in fact based in part on the clinical 7 income which would have derived from those 8 patients. 9 Q Well, I'm not trying to 10 play word games with you, Doctor Thompson; I'm 11 just trying to understand that you've never been 12 an office physician like most of us go to in an 13 office for treatment where we write the doctor a 14 check or give health care benefits to that office 15 that you directly benefit from. 16 A I'm trying to give you an 17 exact answer, and the answer is that most of my 18 patients were, in fact, in intensive care units. 19 However, I also, both at Johns Hopkins and 20 primarily at Case Western Reserve, did in fact 21 maintain an outpatient practice in which patients 22 were billed in my name and I signed those checks 23 if they came to me personally over to a university 24 group; but part of that income did in fact 17 1 determine my salary. 2 Q Was that on some 3 percentage basis? 4 A It was a very complicated 5 formula depending on the total clinical income and 6 so forth; but it would not be proper for me to 7 assert that in fact I had not derived any income 8 from the practice of medicine in the outpatient 9 setting. 10 Q Well, I'm simply wanting 11 to understand if you've ever held yourself out to 12 be a practicing physician in the business of 13 seeing patients for their physical illnesses, 14 where you go to an office, this is Doctor Leigh 15 Thompson's office, you can come in and see me for 16 whatever particular specialty you have, get 17 treatment, and then go back to your home or 18 wherever. 19 A Well, sir, I would have 20 to answer that question that, yes, I have in fact 21 done that. 22 Q When and where? 23 A Well, I began my career 24 at the Johns Hopkins University and Hospital in 18 1 1970. I left Hopkins in 1974 and went to Case 2 Western Reserve University. I left Case Western 3 Reserve University in 1982 and came to Lilly, and 4 since then I have earned no income from the 5 practice of medicine, as you have defined it, but 6 I have as a consultant. 7 Q All right. My dad is a 8 medical doctor, Doctor Thompson. He was a general 9 practitioner in Plainview, Texas. He had an 10 office where he went and saw patients; then he 11 went to the hospital; then he made house calls and 12 came home. You've never had a private practice 13 such as that, have you? 14 A I've tried to very 15 exactly describe the kinds of practice of medicine 16 that I've done. 17 Q Can you not answer that 18 question "yes" or "no", Doctor Thompson? 19 A No, I can't, because you 20 haven't framed it in a fashion that allows a "yes" 21 or "no" answer, because part of your question in 22 fact would be answered "yes" and part of it would 23 be answered "no". 24 You could have come to, 19 1 for example, Case Western Reserve University and 2 asked to see either me by name or been referred to 3 me by another physician by name; I would have seen 4 you in the outpatient department, if you were not 5 in intensive care unit, you would have received a 6 bill in my name, you would have paid the bill in 7 my name, and part of your payment of that bill 8 would have indirectly contributed to the income I 9 received as a full-time University employee. 10 Q Were you on the faculty 11 at Case Western University? 12 A Yes, sir. 13 Q And what was your faculty 14 position? 15 A I had a number of 16 positions. When I went there, I was Associate 17 Professor of Medicine and Associate Professor of 18 Pharmacology. I also later became an adjunct 19 professor in the Department of Library Science, 20 and I was promoted to Professor of Medicine. I 21 had a variety of other titles not in the 22 professorial rank at Case Western Reserve. 23 Q Did you mention library 24 science? 20 1 A That's correct. 2 Q Was that medical library 3 science or just general library science? 4 A Well, the appointment was 5 within the University School of Library Science 6 because of a course that I taught. I also held 7 appointments at other universities during that 8 same interval. 9 Q But you were teaching 10 library science? 11 A I was teaching actually 12 medical infomatics, but it was in fact within 13 library science. 14 Q But was it at -- in 15 connection with research and medical issues? 16 A Yes, sir. 17 Q Let me go back and get a 18 little more detail, Doctor Thompson. You are from 19 where, the South Carolina area? That's where it 20 looks like you started your education. 21 A Yes. I consider myself a 22 native of Charleston, South Carolina, where my 23 family is from, but I was actually born in 24 Shreveport, Louisiana. 21 1 Q Did you come from a 2 family of health care practitioners? 3 A My father was an attorney 4 and electrical engineer and an FBI agent, but many 5 of his -- and his father was a physician, an 6 attorney and an LLD, and most of the line on my 7 father's side were, in fact, lawyers rather than 8 physicians. But other members of my father's 9 family were physicians. I don't believe any of my 10 mother's close family were physicians. 11 Q What year did you 12 graduate from high school? 13 A I never graduated from 14 high school. 15 Q Tell me how that came 16 about; did you take any high school courses? 17 A Yes, sir. I took fifteen 18 courses for credit in high school and it required 19 sixteen to graduate, but I was three years ahead 20 of my class and I entered early the University of 21 Chicago. 22 Q How old were you when you 23 entered the University of Chicago? 24 A I was accepted when I was 22 1 fourteen; when I matriculated, it was after my 2 fifteenth birthday. 3 Q Did you have brothers and 4 sisters? 5 A I have one adopted 6 sister. 7 Q All right. Did you take 8 any courses in psychology in your undergraduate 9 work? 10 A Yes, sir. 11 Q Where? 12 A At the College of 13 Charleston. 14 Q How many courses in 15 psychology did you take there? 16 A Either -- I think it was 17 two one-semester courses. 18 Q How about in your 19 graduate work? 20 A Not in graduate school, 21 per se, but in medical school, of course, I had a 22 variety of educational experiences in psychiatry. 23 Q What courses in 24 psychiatry did you take in medical school? 23 1 A Well, I went through the 2 usual curriculum in psychiatry for the junior and 3 senior years in medicine at Hopkins. So, I had 4 rotations in both years of psychiatric service, 5 which I assume answers the question in terms of 6 courses. 7 Q Did they have an actual 8 course in psychiatry that you took, or did you 9 just -- were you just exposed to psychiatry 10 through your rotation? 11 A That's difficult to 12 answer yes or no. I went through the usual 13 program, which in fact was a period of time 14 dedicated to psychiatry in which we had both 15 lectures and reading, as well as patient 16 experiences. 17 Q All right. 18 A But I received the same 19 training that any other medical student in my era 20 would have received. 21 Q Did you receive any 22 additional training other than what any other 23 medical student would have received? 24 A No, sir. 24 1 Q Have you ever practiced 2 psychiatry? 3 A No, sir. 4 Q Have you ever done any 5 specific reading or research into psychiatric 6 issues? 7 A Yes, sir. 8 Q On your own? 9 A Yes, sir. 10 Q Tell me about that. 11 A Well, this relates to my 12 experience within critical care because at both of 13 the major hospitals where I was director of 14 critical care, a large proportion of my own 15 patients, about twenty-five percent, were in fact 16 admitted because of some suicide attempt or drug 17 overdose, and because of the volume of those 18 patients, I in fact did read extensively in that 19 area, but it was the aspect of psychiatry as 20 specifically related to those kinds of patients. 21 Q Suicidal patients and 22 patients who had taken an overdose? 23 A Suicidal patients who had 24 a medical problem, including something like a drug 25 1 overdose. I would not have taken care of someone 2 who had only a psychiatric illness with no medical 3 problems or someone who perhaps had used a 4 surgical attempt to commit suicide. 5 Q Well, would you call in a 6 psychiatric consult for those patients? 7 A Always, always. 8 Q So you were taking care 9 of their physical problems as a result of their 10 suicide attempts in your critical care aspect of 11 your practice, and then you would call in someone 12 to administer to their psychological problems? 13 A I wouldn't quite restrict 14 my responsibilities that great. I mean, my view 15 as the primary physician for the patient was that 16 I was responsible for all their care and until I 17 transferred them to another physician, I used 18 consultants wherever that was appropriate in terms 19 of helping me care for the patients. 20 Q But you weren't, I guess, 21 giving psychiatric advice to those patients as a 22 psychiatrist? 23 A Well, certainly not as a 24 psychiatrist. 26 1 Q Well, were you giving 2 them psychiatric advice that you had learned in 3 your readings on psychiatry? 4 A I think it very difficult 5 for an internist caring for the entire patient to 6 partition the kinds of advice responsible. Again, 7 my responsibility was for the entire patient, so I 8 would not want to assert that I never gave advice 9 which you would characterize as psychiatric. But 10 I've never held myself out to have any special 11 expertise in psychiatry, nor to practice 12 psychiatry. 13 Q Have you ever prescribed 14 any psychiatric medications? 15 A Yes, sir. 16 Q Have you ever prescribed 17 any antidepressants? 18 A Yes, sir. 19 Q What antidepressants have 20 you prescribed? 21 A Primarily tricyclics 22 because, as I explained earlier, most of my actual 23 patient care experience ended in 1982, and 24 therefore it was largely the tricyclics that were 27 1 available at that time. 2 Q And in what circumstances 3 would you prescribe the antidepressants? I mean, 4 were you -- was this part of your function as a 5 critical care physician? 6 A Well, it could be both 7 within the critical care as well as the outpatient 8 function which I described earlier. 9 Q All right. On how many 10 occasions would you -- do you think that you 11 prescribed antidepressant medications? 12 A Over my entire career, my 13 guess would be perhaps three dozen times, three 14 dozen patients. 15 Q Thirty-six, 16 approximately? 17 A Somewhere in that ball 18 park. 19 Q Did you ever have any 20 adverse experiences with any -- administering any 21 of those antidepressant medications? 22 A Yes, sir. 23 Q What experiences did you 24 observe as a result of administering those 28 1 medications? 2 A Well, let me say that 3 there are two ways to answer that. One is the 4 medicines that I, myself, prescribed and my memory 5 is of only relatively minor side effects, such as 6 dry mouth, constipation, postural hypertension I 7 recall once. However, a fair proportion of the 8 patients that I cared for in the intensive care 9 unit with drug overdoses had, in fact, taken 10 overdoses including tricyclics or monamine oxidase 11 inhibitors, and therefore I got to take care of 12 people with very serious side effects from those 13 medicines, even though I hadn't prescribed them 14 myself. 15 Q Well, did you consider 16 those overdose as side effects -- those overdose 17 attempts as side effects from the medication? 18 A Yes, sir. 19 Q In what respect? 20 A Well, my definition of a 21 side effect would be any adverse event that 22 happens after the intent to treat the patient with 23 a drug, so that if a physician had intended to 24 give Elavil as a tricyclic to a patient and they 29 1 had an adverse event, one that wasn't desired or 2 expected, I would call that an adverse event or a 3 side effect. 4 Q Well, would you attribute 5 those adverse events as causally related to the -- 6 for instance, the Elavil? 7 A Causation is particularly 8 difficult in medicine to establish in an 9 individual patient, and so in part that answer 10 would depend upon the characteristics of the 11 adverse event, its temporal relationship to the 12 administration and the dose of Elavil. So in some 13 cases in which a syndrome developed that had been 14 reported many times before in patients who had 15 taken overdoses of that tricyclic, I would say 16 that I was at least prompted towards saying that 17 the relationship between the drug and the side 18 effects were -- was highly likely. 19 Q In other words, the drug 20 was causing the individual to take the overdose, 21 is that what you're saying? 22 A Well, I don't want to be 23 pedantic on this, but causation is a particularly 24 difficult thing to assign in medicine to an 30 1 individual patient. It is much easier to look at 2 the probability that occurs when a number of 3 patients have taken the drug and have similar 4 kinds of events. 5 Q Well, that may be true, 6 but don't you, as a physician, want to examine 7 whether or not a particular individual's 8 particular problem is a result of a particular 9 medication? 10 A You would very much like 11 to establish that, but it is very difficult, 12 perhaps even close to impossible to establish with 13 certainty the causation. So that when I wrote 14 down my opinions of a patient, I might say that 15 this is possible or probable, or even very 16 probable, but I don't recall very many times when 17 I've said that this condition is certainly caused 18 by an antecedent drug. 19 Q And my question wasn't 20 whether or not it was certainly cause -- whether 21 it was causally related in any way, have you 22 observed any adverse events causally related to 23 ingestion of a particular drug? 24 MR. FREEMAN: You're not 31 1 limiting yourself to suicide or including 2 suicide? 3 MR. SMITH: Oh, no. 4 A Well, I believe that the 5 probability that some of the events that I saw 6 were causally related was high; higher than 7 fifty-one percent. 8 Q All right. And what 9 generally did you take into account in determining 10 a probability greater than fifty-one percent? 11 A The exact nature of the 12 event that I was observing and the frequency with 13 which that event had been seen both in patients 14 who had taken a similar dose of drug and in those 15 who had not taken that dose of the drug. 16 Q All right. 17 A Because of the temporal 18 relationship; I mean, obviously if the event began 19 before the dose of a drug were taken, that would 20 change one's probability assessment a great deal. 21 Sometimes the course of the event in terms of how 22 it wears off, sometimes patients take a drug again 23 and if an event often occurs on repeated dosing 24 and it's exactly the same, then one would increase 32 1 the probability that they're causally related. 2 Q Anything else? 3 A I think that's primarily 4 it. 5 Q We'll get back to that 6 later on, Doctor Thompson. 7 We've been introduced, my 8 name is Paul Smith, and I represent a number of 9 individuals, Doctor Thompson, whose lives have 10 been affected by virtue of their or their loved 11 one's ingestion of the drug fluoxetine 12 hydrochloride, Prozac, manufactured by Eli Lilly 13 and Company; do you understand that? 14 A I understand you, 15 Mr. Smith, that you represent some individuals. 16 Q And your deposition is 17 being take here and will be used at trial in these 18 cases, do you understand that? 19 A Yes, sir. 20 Q Have you had an 21 opportunity to speak with your attorneys 22 concerning what a deposition is and things of that 23 nature? 24 A Yes, sir, I have. 33 1 Q When did you meet with 2 your attorneys concerning this deposition? 3 A Over the last month. 4 Q On how many occasions? 5 A Approximately five or 6 six. 7 Q And who did you meet with 8 on those occasions? 9 A Several Lilly attorneys, 10 as well as the distinguished attorneys to my 11 right. 12 Q Both distinguished 13 attorneys or just one of the distinguished 14 attorneys to your right? 15 A I think they're both 16 distinguished. 17 Q All right, you met with 18 both Mr. Myers and Mr. Freeman? 19 A Yes, sir. 20 Q And how much time have 21 you spent with Mr. Myers -- 22 A Several -- 23 Q -- in preparation for 24 your deposition? 34 1 A Several hours. 2 Q What do you consider 3 several hours? 4 A Three or four. 5 Q And when did you last 6 meet with Mr. Myers in connection with your 7 deposition? 8 A Monday morning of this 9 week. 10 Q And how long did you all 11 meet? 12 A Oh, two hours or so at 13 that time. 14 Q And then have you met 15 with Mr. Myers concerning your deposition since 16 then? 17 A Only this morning when I 18 arrived. 19 Q And how about the older 20 distinguished attorney to your right, Mr. Freeman; 21 have you met with Mr. Freeman recently concerning 22 your deposition? 23 A Well, in addition to this 24 morning, once in the last several weeks. 35 1 Q And how long did you meet 2 with Mr. Freeman? 3 A Approximately an hour. 4 Q How long did you all meet 5 this morning? 6 A I arrived not long after 7 8:00, and I believe you arrived a little bit after 8 9:00. 9 Q Have you met with any 10 other non-Lilly lawyers -- when I say non, 11 in-house Lilly lawyers -- concerning your 12 deposition, Doctor Thompson? 13 A No, I believe the lawyers 14 that I met with were in-house, but actually I'm 15 not a hundred percent certain of that. 16 Q Have you reviewed any 17 documents in preparation for your deposition? 18 A Yes, sir. 19 Q What documents have you 20 reviewed? 21 A The attorneys have asked 22 me questions about a number of documents, some of 23 which I had authored and some of which I had not 24 seen before. 36 1 Q Did you actually see 2 those documents? 3 A Yes, sir. 4 Q And can you give me an 5 estimate of the number of those documents? 6 A Somewhere in the forty 7 range. 8 Q And when did you first 9 begin reviewing documents in preparation for your 10 deposition? 11 A I believe it was either 12 three or perhaps four weeks ago. 13 Q And was Mr. Myers with 14 you at that time or was this with some Lilly 15 in-house lawyers? 16 A Mr. Myers was present 17 once, and I can't remember the exact sequence. I 18 believe that the first couple of meetings were 19 with whom I believed to be Lilly attorneys. 20 Q A file was produced -- or 21 documents were produced reportedly from your file, 22 Doctor Thompson. 23 A Yes, sir. 24 Q Did you review those 37 1 documents before they were turned over to the 2 legal department? 3 A No, sir, I found all of 4 the documents that I had in my possession that 5 were relevant and turned them over, but I don't -- 6 I wouldn't say I reviewed any of them other than 7 to identify their content. 8 Q All right. Have you had 9 any practice sessions where you've practiced in 10 connection with giving testimony? 11 MR. FREEMAN: Don't 12 answer that question. 13 Q Where people have fielded 14 questions to you that might purportedly be asked 15 of you in this deposition? 16 MR. FREEMAN: I instruct 17 the witness not to answer that question. 18 MR. SMITH: By anybody, 19 I'm not limiting it to lawyers. 20 MR. FREEMAN: He's had no 21 practice sessions with anybody other than perhaps 22 there may have been some work product done in 23 connection with that, and I'm not going to let him 24 answer the question. 38 1 Q (BY MR. SMITH) Well, 2 we've seen some documents, Doctor Thompson, where 3 you've practiced and you've had rehearsals in 4 connection with appearances for 20/20 or various 5 news programs, documents where Mr. West, Ed West 6 from your corporate communication department and 7 Mr. and Mrs. Daniels have been with you and 8 critiqued your performance in those practice 9 sessions. Do you recall those situations where 10 you did that, Doctor Thompson? 11 A Yes, sir. 12 Q Have you done anything 13 such as that for this deposition? 14 MR. FREEMAN: You can 15 answer that question as it relates to anybody 16 other than lawyers representing Eli Lilly and 17 yourself. 18 A No. 19 Q If I ask you any 20 questions that you're unsure of or you're unclear 21 of with respect to the meaning of my question, 22 would you let me know, sir? 23 A Yes, sir. 24 Q English is your first 39 1 language? 2 A Yes, sir. 3 Q Do you speak other 4 languages? 5 A Not very well. 6 Q Do you speak at some 7 other languages, as we say down in Texas? 8 A Well, I was trained in 9 French in college, and I've passed language 10 examinations in French and German, but I don't 11 think I'm fluent in either one. 12 Q Before you began with 13 Lilly in 1982 -- is that when you say you started 14 with Lilly? 15 A Yes, sir. 16 Q Had you worked for any 17 other pharmaceutical company? 18 A Not as a full-time 19 employee, but I did have grants from other 20 pharmaceutical companies for both research as a 21 consultant and as a lecturer. 22 Q Had you done clinical 23 trials for other pharmaceutical companies? 24 A Yes, sir. 40 1 Q If you can, give me a 2 list of the companies and the medication, if that 3 medication was actually marketed as opposed to not 4 marketed, of any clinical trial work that you 5 participated in, Doctor Thompson, prior to joining 6 Lilly. 7 A That would be a very long 8 list; let me see if I can reconstruct some of it 9 because I think that I probably did clinical 10 trials with at least twenty different companies. 11 Some of the products that were involved, that I 12 can recall, was with Buringa Ingelhime, a 13 cardiovascular antidysrhythmic drug called 14 mexiletin which has since been marketed. 15 I did clinical trials 16 sponsored by Sherring on gentamycin, an 17 antibiotic. I did clinical trials with other 18 aminoglycoside antibiotics for other companies, 19 and I'm struggling for which company, and I don't 20 remember which company -- I think it's Bristol 21 Myers, at that time, amikacin, for which I did 22 trials. 23 I did trials with several 24 antihypertensive drugs, and I think Burke was one 41 1 of the sponsors for those, and I don't really 2 remember which exact one it was. I recall also 3 doing sponsored research, both preclinical 4 research as well as clinical research, with 5 Burroughs Wellcome, with Upjohn. That was with a 6 prostaglandin; specifically it was both 7 prostacyclin, which I don't -- I'm sorry, I think 8 it is marketed now, and prostaglandin E. I also 9 did some experimental work with prostaglandin 10 F2-Alpha, and that has not been marketed to my 11 knowledge. 12 Q What type of drug is 13 that? 14 A Well, prostacyclin is a 15 vasodilator. Prostaglandin E has a whole variety 16 of effects, including the induction of labor, and 17 can cause vasoconstriction or vasodilation. 18 Prostaglandin F2-Alpha causes platelet reactions 19 and vasoconstriction primarily. Some of that work 20 was also sponsored by Burroughs Wellcome. 21 The only work that I had 22 done with Lilly was some sponsorship of -- I know 23 there was actually both preclinical and clinical 24 work done with Lilly on tobramycin, which is an 42 1 antibiotic. And then of course I did a lot of 2 work with my own invention, hydroxyethyl starch, 3 which was sponsored at various times by different 4 components of American Hospital Supply 5 Corporation, depending on who owned the patent at 6 the time; originally with McGraw Laboratories, 7 which became a part of American Hospital Supply, 8 and then what used to be called Honorstone, which 9 was subsequently sold to Dupont Critical Care. 10 I've also done a great 11 deal of both clinical and preclinical work with 12 dopamine which was being developed by Honorstone; 13 again, which was, I think, during most of that 14 period, a part of American Hospital Supply, but 15 now is owned by Dupont. 16 Q Were you the principal 17 investigator on any of the drugs that you 18 mentioned? 19 A Oh, on the individual 20 grants that I held, I think I was principal 21 investigator on all of those. 22 Q All right. Had you been 23 involved in any clinical trials in any way prior 24 to coming to Lilly involving antidepressant 43 1 medications? 2 A I don't believe so. 3 Q But you had not been 4 employed full time as an employee of any 5 pharmaceutical firm prior to joining Lilly? 6 A Certainly not a full-time 7 employee, but again, I was paid as part of a 8 grant, as part of a consultant fee for my 9 services, or as part of an honorarium for a 10 lecture, for example. 11 Q But that was never your 12 primary source of income? 13 A No, sir. 14 Q But since you've been 15 with Lilly, that's been your primary source of 16 income, has it not? 17 A Yes, sir. 18 Q What was your last 19 position before you joined Lilly? 20 A At Case Western Reserve 21 University, where my academic positions in the 22 University we've discussed already. I had a 23 number of other positions there as a member of the 24 faculty senate and a variety of committees. I 44 1 also had a number of positions primarily at 2 University Hospitals of Cleveland, such as 3 Director of Critical Care, Director of Clinical 4 Pharmacology, Director of the Drug Information 5 Center, Director of the Drug Analysis Laboratory, 6 and Director of the Northeast Ohio Poison Center. 7 Q Why did you leave all 8 that to come to Lilly? 9 A Why? 10 Q Uh-huh. 11 A Well, Lilly had such an 12 exciting research laboratories, and I was vitally 13 interested in research and helping people, I 14 thought that that would be an exciting opportunity 15 for me. 16 Q Well, it sounds to me 17 like you were involved in research at Case Western 18 University and you were involved in helping people 19 at Case Western University. 20 A Yes, sir, I was. 21 Q Why did you want to 22 change? 23 A I'm not sure I wanted to 24 change, sir. I was very happy doing what I was 45 1 doing. 2 Q Did they come after you 3 or did you seek Lilly out? 4 A No, they came after me, 5 sir. 6 Q Who approached you from 7 Lilly to join Lilly? 8 A I think the first contact 9 was made by Ian Shedden. 10 Q How did you come into 11 contact with Mr. Shedden? 12 A That's Doctor Shedden, 13 and I think my first contact with him was as a 14 speaker at some research seminars that Lilly had 15 sponsored in relation to my work where I mentioned 16 earlier that I'd worked with tobramycin, which is 17 a Lilly product, and gentamicin and amikacin, and 18 I think it was at a seminar related to those 19 studies that I first met Doctor Shedden. 20 Q Had you expressed to 21 Doctor Shedden an interest in possibly leaving 22 Case Western? 23 A No, sir. 24 Q Did he tell you why he 46 1 was seeking you to potentially join Eli Lilly and 2 Company in Indianapolis? 3 A Well, he said he thought 4 my skills would be of value to Lilly. 5 Q Was there a particular 6 position that he was suggesting for you? 7 A Yes, sir. 8 Q What was that? 9 A It was as Director of 10 Clinical Investigation, and the scope of that job 11 specifically was with responsibility for what we 12 called at that time phase two and three clinical 13 investigation in the United States. 14 Q All right. Who else did 15 you talk with? I assume that Doctor Shedden 16 wasn't the only individual that you talked with 17 before joining Lilly. 18 A No, I would say that the 19 primary recruiting team included Doctor Earl Herr, 20 to whom Doctor Shedden reported, but I also talked 21 with a number of scientists at Lilly, for example, 22 Doctor Lou Lemberger who was a fellow clinical 23 pharmacologist that I had known for some time and 24 who I visited before at the Lilly Clinic. 47 1 There was also people 2 from Human Resources obviously, and I must have 3 met with at least a dozen different scientists at 4 Lilly. Cecil Bendish was one, Chris Christensen 5 was another, and that's about as far as I can 6 recall people that I met with. 7 Q Why did you decide to 8 finally leave Case Western University and join Eli 9 Lilly and Company? 10 A Well, I was in the -- 11 first of all, I didn't want to leave, I was very 12 happy. I had been offered three other jobs. My 13 best friend was my chairman and boss at Case 14 Western Reserve, he was only a couple of years 15 older than I, so if I were to in fact be promoted 16 to a department chairman, it would be most likely 17 that I would have to leave Case Western Reserve, 18 and I was looking at jobs both at UCLA and at 19 South Carolina and had been asked to take over the 20 Bureau of Drugs, as it was then called, at the 21 FDA. So I was looking at those opportunities when 22 Lilly called me, and quite frankly I went in to 23 talk with my boss at Case Western Reserve and told 24 him I didn't want to leave, but here were four 48 1 career opportunities that I was being offered, and 2 I sought his advice out. And he thought that for 3 my career advancement at the time that it would in 4 fact be appropriate for me to think of leaving his 5 department, and of the various opportunities we 6 talked through, he actually suggested that Lilly 7 might have the greatest opportunity for me to 8 contribute with my skills to research and to help. 9 Q And so when did you 10 actually start with Lilly? 11 A April the 1st of 1982. 12 Q And your first title was 13 Director of Clinical Investigation? 14 A Yes, sir. 15 Q How long did you hold 16 that title? 17 A For about six months. 18 Q Then what title did you 19 assume? 20 A Executive Director of 21 Lilly Research Laboratories. 22 Q What did that position 23 entail? 24 A Well, it included the 49 1 former position, and also included greater 2 responsibility for regulatory affairs that at the 3 time was somewhat separate, and for what we then 4 were calling phase four research as well in the 5 United States. 6 Q All right, so April -- so 7 it will have still been in '82 when you became the 8 executive -- was it the Executive Director of 9 Lilly Research Labs? 10 A No, sir, it was -- 11 Q An executive? 12 A An executive director. 13 Q There were other 14 executive directors? 15 A Yes, sir. 16 Q Who were some of the 17 other executive directors at the time? 18 A Emerson Houck, H-O-U-C-K, 19 was also responsible within the medical research 20 community at that time. I'm not sure I can name 21 any of the other executive directors at that time. 22 Q How long were you an 23 executive director of Lilly Research Labs? 24 A About two or three years. 50 1 Q So we're now going into 2 1985? 3 A Approximately. 4 Q What was your next job 5 with Lilly? 6 A I was then promoted to a 7 vice president of Lilly Research Laboratories. 8 Q How long did you hold 9 that position? 10 A My job description 11 changed several times with that same title, but I 12 think it was a total of about three years before 13 my next promotion. 14 Q You mean 1988, then? 15 A Roughly 1988. 16 Q You say your job title 17 changed a couple of times. 18 A Yes, sir. 19 Q Tell me what those 20 changes were. 21 A Well, Lilly gradually 22 added to my responsibilities, so that I gradually 23 became responsible for more of the staff that were 24 working in medical research, medical systems. I 51 1 became responsible for toxicology, eventually for 2 project management, then responsible for the phase 3 one research effort at the Lilly Clinic. I think 4 that was most of the changes at that time. 5 Q This sounds to me 6 primarily a management job. 7 A Well, yes, sir. 8 Q This was overseeing 9 clinical research, overseeing pharmaceutical 10 research as opposed to actually being involved 11 with it? 12 A Yes, sir, except we tend 13 to use the word pharmaceutical research to refer 14 specifically to things like process chemistry, and 15 that's an aspect of research I've never been 16 responsible for. 17 Q All right. Then after 18 1988, what was your next promotion? 19 A I was made a group vice 20 president, at that time, of Lilly Research 21 Laboratories. 22 Q Did that mean that there 23 was other vice presidents who were reporting to 24 you? 52 1 A Yes, sir. 2 Q All right. Up to that 3 time, had other vice presidents of Lilly Research 4 Labs reported to you? 5 A Yes. 6 Q All right, who? 7 A I think -- it's difficult 8 for me to remember exactly the sequence of events, 9 but I think that Doctor Morton, for example, who 10 is a vice president of Lilly Research 11 Laboratories, reported to me -- he certainly 12 reported to me, I think it was before I became 13 group vice president, it could have been after 14 that period. 15 Q All right. After you 16 became group vice president, who was reporting to 17 you? 18 A Well, I had part of 19 discovery research reporting to me, and that was 20 Vice President Doctor John Whitney. I had Erl 21 Wood research, which was based in England. That 22 also reported through Doctor Whitney. At that 23 time for sure I had Doctor Morton, who was 24 responsible for toxicology. Vice President Doctor 53 1 Pat Raffe, who was responsible for project 2 management. Initially as I recall, I had Doctor 3 Zerbe and Doctor Reed, both of whom were promoted 4 to vice president about that time. I think that's 5 about the list. 6 Q What was Doctor Zerbe's 7 position? 8 A Well, it changed over 9 time. I had asked him to be responsible at one 10 time primarily for the CNS research division when 11 I reorganized the medical component into a 12 therapeutic approach, and then he became 13 responsible for the medical group at Erl Wood, and 14 then he became responsible for the whole research 15 laboratories at Erl Wood Manor, and then he came 16 back to this country. 17 Q When he came back, what 18 was his title? 19 A Well, when he came back, 20 he came back as a vice president, and at that 21 time, initially, he was primarily responsible 22 within the medical group for a major component of 23 medical. 24 Q How long were you vice 54 1 president of Lilly Research Labs? 2 A It was either two or 3 three years. 4 Q '90 to '91? 5 A Somewhere between '90 6 and '91. 7 Q And what was your next 8 job? 9 A I was then promoted to 10 executive vice president; and, as a matter of 11 fact, that was in '91. 12 Q Executive vice president 13 of -- 14 A Of Lilly Research 15 Laboratories. 16 Q And how were your job 17 duties expanded at that time? 18 A At that time I became 19 responsible for most of Lilly Research 20 Laboratories, except for that that was reporting 21 to Doctor Tom Emmick, a vice president who also, 22 as I did, reported to Doctor Perelman, and he was 23 responsible largely for the process chemistry and 24 for the support and manufacturing and production 55 1 both of bulk drug substance and fill finish in 2 terms of the science. I never have had 3 responsibility for that part of Lilly, but all the 4 other parts of Lilly Research reported to me at 5 that time. 6 Q The actual manufacture 7 was never part of your responsibility? 8 A No, sir, but Doctor 9 Emmick also supported the science of devising the 10 actual formulations and the analytical tests to 11 see what the constituents were, something that we 12 tend to call process chemistry. And again, I 13 never was responsible for that piece of the Lilly 14 Research Laboratories. 15 Q Well, maybe I'm not 16 clear, then. We know that Doctor Fuller and 17 Doctor Wong were responsible for the formulation 18 and testing early on of Prozac, fluoxetine 19 hydrochloride. Would this have been something 20 that -- had it been done under your -- at your 21 time with Lilly, would that have been something 22 that you would have been involved in or Doctor 23 Emmick would have been involved in? 24 A Well, you used the word 56 1 formulation. I don't think that in fact Doctor 2 Fuller or Doctor Wong were involved with the 3 actual construction of the material that we used 4 for testing and toxicology and in clinical 5 trials. They were part of discovery that did 6 report to me, both as a group vice president and 7 as an executive vice president. 8 Q All right. 9 A So they clearly -- Doctor 10 Mulloy clearly synthesized the molecule first, and 11 Doctors Wong and Fuller certainly did the 12 biological testing. What I meant by process 13 chemistry was when we go into toxicology or into 14 clinical trials, there's actually a great deal of 15 science that has to be done with inert 16 ingredients, excipients, capsules, tablets, 17 dissolution rates, looking at how you actually 18 find the molecule and its metabolites, and that 19 largely has been the job of Doctor Emmick. 20 Q Okay. I was unclear as 21 to what that particular phase involved. All 22 right, so how long were you executive vice 23 president of Lilly Research Labs? 24 A Until January of 1992. 57 1 Q What happened in January 2 of -- 3 A No, I'm sorry, 1993. 4 I've been in my present position for a year and a 5 half. 6 Q All right. What is your 7 present position? 8 A I'm called the Chief 9 Scientific Officer of Eli Lilly and Company. 10 Q Who do you report to now? 11 A To the Chairman and Chief 12 Executive Officer. 13 Q Mr. Tobias? 14 A Yes, sir. 15 Q And who did you report 16 to -- or have you reported to anybody else since 17 January 1993 as the chief scientific officer of 18 Eli Lilly and Company? 19 A I reported to Mr. Vaughn 20 Bryson. 21 Q Before he left? 22 A Yes, sir. 23 Q Let's see, Richard Wood 24 retired in October of 1991, did he not? 58 1 A I don't know the exact 2 date. 3 Q Does that sound 4 approximately right? 5 A I think that Mr. Tobias 6 assumed the role as Chairman and President, CEO, 7 in June of 19 -- June of last year, 1993. 8 Q Who did you report to 9 when you were executive vice president of Lilly 10 Research Labs? 11 A Doctor Mel Perelman. 12 Q He was the President? 13 A Of Lilly Research 14 Laboratories, yes, sir. 15 Q And when you were a group 16 vice president, were you also reporting to Doctor 17 Perelman? 18 A Yes, sir. 19 Q Anybody in between you 20 and Doctor Perelman, or did you report directly to 21 him? 22 A No, sir, I reported 23 directly to Doctor Perelman. 24 Q And when you were a 59 1 director of Lilly Research Labs, who did you 2 report to? 3 A I reported to Doctor 4 Shedden originally, and when he left, I reported 5 to Doctor Christensen for awhile, and then he 6 retired and then I reported to Doctor Herr. 7 Q Doctor Herr? 8 A Yes, sir. 9 Q And when you were 10 director of clinical investigation -- 11 A Oh, I'm sorry, during 12 that period I reported to Doctor Shedden, during 13 the entire period I was in that job. 14 Q What do your duties now 15 entail as the Chief Scientific Officer of Eli 16 Lilly and Company? 17 A It's primarily in a staff 18 advisory role to the Chairman, to other members of 19 the management committee of the corporation. I am 20 involved in recruiting scientists. I am involved 21 in academic contact for the corporation. I'm 22 involved in the current health care debate, both 23 speaking with and participating in political as 24 well as layperson and professional groups. I try 60 1 to find exciting scientific opportunities for us 2 and participate in the evaluation thereof. I also 3 am specifically responsible for three areas: One 4 of these is health economics and epidemiology, one 5 is medical decision quality, and the third is 6 health infomatics. 7 Q Give me those last two 8 again. 9 A I'm sorry -- 10 Q Number one was health 11 economics? 12 A And epidemiology, one is 13 medical decision quality, and the third is health 14 infomatics. 15 Q Are you in any way 16 involved in Lilly Research Labs anymore? 17 A I don't have line 18 responsibility for anyone in Lilly Research 19 Laboratories, but obviously a great deal of my 20 work continues with science and research, so I 21 participate in a number of the committees and 22 evaluation of a number of opportunities and so 23 forth. But there's no one who works within Lilly 24 Research Laboratories who reports directly to me 61 1 in this job. 2 Q Who is now the president 3 of Lilly Research Labs? 4 A Doctor August Watenaby. 5 Q And he doesn't report to 6 you? 7 A No, sir. 8 Q And you don't give him 9 directions or instructions? 10 A Advice at most. 11 Q Does he consider that as 12 advice or directions or instructions? 13 A Oh, no, that would be 14 only as an advisor. 15 Q Do you have a staff 16 currently? 17 A Yes, sir. 18 Q How many people do you 19 have on your staff? 20 A Roughly forty-five. 21 Q And are they divided up 22 in some way? 23 A Yes, sir. 24 Q How? 62 1 A There are two people that 2 report directly to me, other than my secretary; 3 one is responsible -- 4 Q You probably report to 5 your secretary, don't you? 6 A I certainly do. 7 Q All right. 8 A One is primarily 9 responsible for the decision quality and the 10 health economics, epidemiology portion, and the 11 other is primarily responsible for health 12 infomatics. 13 Q Are you an officer of the 14 corporation? 15 A I think I'm regarded as 16 an officer of the corporation, yes. 17 Q Since you are the chief 18 scientific officer, that is an officer at Eli 19 Lilly and Company, is that correct? 20 A That's my understanding, 21 yes, sir. 22 Q And do you sit on the 23 board of directors of the company? 24 A No, sir, I do not. 63 1 Q But you are an officer of 2 the corporation? 3 A That's my understanding. 4 Q And as an executive vice 5 president of Lilly Research Labs, were you an 6 officer of Eli Lilly and Company? 7 A I have never been 8 specifically told whether I was or was not an 9 officer, but I have inferred from some of the 10 responsibilities that I was given that I was, in 11 fact, being treated as an officer. 12 Q While you were executive 13 vice president of Lilly Research Labs? 14 A Yes, sir. 15 Q And how long were you 16 being treated as an officer? I mean, when did -- 17 was that when you became executive vice president 18 in 1991, or were you also treated as an officer of 19 the corporation when you were a group vice 20 president? 21 A I think that was also 22 true. 23 Q All right. How about 24 back as early as 1985, when you were -- held the 64 1 position of vice president of Lilly Research Labs, 2 were you treated as a corporate officer then? 3 A Again, I am inferring 4 from other kinds of responsibilities that I was 5 given, but I have never explicitly been told that 6 I was or was not an officer of the corporation, so 7 you'll have to accept my inference that at the 8 time I became a vice president that I began to be 9 treated as an officer of the corporation. 10 Q When did Doctor Perelman 11 retire? 12 A He retired at the end of 13 last year. 14 Q So Doctor Perelman was 15 president of Lilly Research Labs when you became 16 the chief scientific officer of Eli Lilly and 17 Company? 18 A Yes, sir. 19 Q Had there been a chief 20 scientific officer of Eli Lilly and Company prior 21 to you? 22 A I don't believe so. 23 Q Do you know why you were 24 named chief scientific officer of the corporation? 65 1 A Well, Mr. Bryson 2 described a new set of responsibilities and asked 3 me to fill it and said that was the title that he 4 wanted me to have. 5 Q Did you continue to make 6 presentations to the board of directors of Eli 7 Lilly and Company? 8 A Yes, sir. 9 Q And you've been making 10 presentations to the board of directors of Eli 11 Lilly and Company for some time, have you not? 12 A Yes, sir. 13 Q When do you recall first 14 making a presentation to the board of directors? 15 A I'm not sure about 1982, 16 but I'm reasonably certain that I first met that 17 group certainly by 1983. 18 Q When you say "met that 19 group", went into a room where they were meeting 20 as -- 21 A Yes, sir. 22 Q -- directors of the 23 corporation? 24 A Yes, sir. 66 1 Q As opposed to informally? 2 A Yes, sir. 3 MR. SMITH: Let's take a 4 quick break. 5 (SHORT BREAK TAKEN.) 6 MR. BOUR: The time is 7 10:28. 8 Q (BY MR. SMITH) What 9 stages was Prozac in when you first joined Lilly, 10 Doctor Thompson? 11 A When I first joined 12 Lilly, the New Drug Application studies were being 13 completed, and not long after I joined there was 14 actually work going on to put the first New Drug 15 Application together. 16 Q I believe the actual NDA 17 was submitted in September of 1983; does that 18 sound -- 19 A I think that's right. 20 Q -- approximately correct 21 as far as you're concerned? 22 A Yes, sir. 23 Q Why don't you give us 24 generally what that New Drug Application is, from 67 1 your standpoint? 2 A A New Drug Application in 3 the United States, for the Food and Drug 4 Administration, is a description of virtually all 5 of the scientific information that's known about 6 the drug, including everything from its chemistry, 7 pharmacology, toxicology, and all of the clinical 8 trials that have been performed, as well as things 9 such as proposed labeling and conclusions from all 10 those data. 11 Q The New Drug Application 12 was submitted on fluoxetine hydrochloride, Prozac, 13 in September of 1983; however, the Food and Drug 14 Administration didn't give Lilly approval to 15 market the drug until December 1987, correct? 16 A That's correct, sir. 17 Q So what happens during 18 that three -- that four-year period of time almost 19 that -- and I'm assuming you're at Lilly and 20 directly or indirectly involved in this 21 application throughout that period of time, were 22 you not? 23 A Yes, sir. 24 Q All right. What happens 68 1 during that period of time? 2 A Well, on the side of the 3 sponsor, such as Lilly, continued studies go on, 4 again throughout all the phases of research with 5 the product. On the side of the Food and Drug 6 Administration, they divide the application up 7 into segments, and each segment is assigned to a 8 different reviewer, and at different speeds those 9 reviewers begin to review the material and then 10 periodically ask questions, either through 11 telephone call or facsimile or a letter, and the 12 company responds to those questions, and there are 13 often meetings that are held to discuss things 14 that have come up. They request additional 15 analyses; sometimes they request completely whole 16 new studies. 17 Q In connection with 18 Prozac, when the New Drug Application was 19 submitted in September 1983, is it correct that 20 Lilly felt like that Lilly had researched the drug 21 sufficiently to support the granting of the 22 application as of September 1983? 23 A Oh, yes, sir. 24 Q In other words, by 69 1 September 1983, the Lilly scientists were of the 2 opinion, based on the work that they had done in 3 connection with this product, that the drug could 4 be marketed as of September 1983? 5 A Yes, sir. 6 Q All right. However, that 7 doesn't mean that Lilly had stopped all their 8 clinical trials on Prozac, does it? 9 A Oh, no, sir. 10 Q And there were clinical 11 trials that had been completed as of September 12 1983, correct? 13 A Yes, sir. 14 Q But there were also other 15 clinical trials that were ongoing as of that date, 16 the date the New Drug Application was submitted? 17 A I think there was some 18 that were ongoing. There were certainly some that 19 were started around that same date. 20 Q Certainly, after 21 September '83, many new clinical trials had been 22 started? 23 A Yes, sir. 24 Q As of September 1983, 70 1 however, there were clinical trials that had been 2 done by Lilly that Lilly felt met the requirements 3 that would support the granting of the right to 4 market Prozac, correct? 5 A Yes, sir. 6 Q Those studies that were 7 felt by Lilly to support the safety and efficacy 8 of the product were what were considered pivotal 9 studies, is that correct? 10 A Some of them would be 11 called pivotal studies. 12 Q Well, weren't all the 13 pivotal studies completed by September of '83? 14 A All those that were in 15 the original New Drug Application were completed 16 by then. 17 Q Do you know of any new 18 studies that were done after September 1983, 19 Doctor Thompson, that were considered by the 20 United States Food and Drug Administration as 21 being pivotal studies? 22 A I don't remember that 23 with certainty, but they usually make that 24 distinction in things like the summary basis of 71 1 approval or advisory committee meetings, and I 2 honestly don't know which studies they designated 3 as, in their minds, pivotal. 4 Q We hope we've pretty well 5 reviewed that material, and we've taken thirty or 6 forty depositions of individuals like Max Talbott, 7 the director of regulatory affairs, and it's my 8 impression that all of the pivotal studies had 9 been completed by September 1983. Would you have 10 any reason to doubt that, in connection with 11 Prozac? 12 A No, but the distinction 13 between a pivotal study and other studies that 14 contribute to the body of knowledge is somewhat an 15 arcane distinction that is made more by the Food 16 and Drug Administration than by the sponsor. 17 Q That's not Lilly's 18 distinction then, that's an FDA distinction, 19 pivotal versus nonpivotal? 20 A Primarily, although 21 you're asked to identify the studies under the 22 regulation and law that -- on which you're basing 23 the primary data that would support the safety and 24 efficacy of the drug. 72 1 Q And I guess my question 2 or point is, that had been done by September 1983, 3 as far as you're concerned, hadn't it, Doctor 4 Thompson? 5 A Sufficient studies had 6 been done to establish the safety and efficacy 7 appropriate for marketing of the product at the 8 time we submitted the New Drug Application in 9 September of 1983, yes, sir. 10 Q But that did not relieve 11 Lilly from completing the clinical trials that 12 were ongoing, did it? 13 A I don't understand the 14 word relieve. 15 Q You don't stop doing 16 clinical trials just simply because you've 17 submitted your NDA and simply because you think 18 that the NDA is sufficient for approval, do you? 19 A It has not been the 20 practice of Lilly to stop clinical trials. But 21 when you say relieve, it suggests that there's 22 some responsibility to do so, and I don't believe 23 we were ever under any sort of responsibility for 24 conducting additional trials. I think that was an 73 1 option that the corporation exercised. 2 Q All right. In other 3 words, you could have -- as far as you understand 4 the regulations, have stood on the data submitted 5 as of September 1983? 6 A Yes, sir, I believe that 7 to be true. 8 Q And everyone at Lilly, 9 that is the management, felt that the data was 10 sufficient to support the application at the time 11 it was submitted in September '83? 12 A I can't assert for 13 everyone at Lilly; there was no dissent that I can 14 recall that we had not completed sufficient 15 studies that establish the safety and efficacy. 16 Q Did you have any 17 responsibility for approval of the NDA as it was 18 submitted in September 1983? 19 A Yes, sir. 20 Q What was your 21 responsibility, sir? 22 A Well, I was responsible 23 for the components that were both creating the New 24 Drug Application and through the regulatory group 74 1 doing some of the quality control and quality 2 assessment of that application. 3 Q All right. Does that 4 mean you were responsible for the final scientific 5 review as well as the regulatory component? 6 A I was one of a large 7 number of individuals who had that responsibility, 8 yes. 9 Q Well, who had more 10 responsibility in connection with submitting the 11 NDA than you, sir? 12 A Well, this is really a 13 joint responsibility because this is an enormous 14 document, and there are parts of it that come from 15 research for which I neither had any management 16 responsibility nor even any particular expertise; 17 for example, the process chemistry is one example, 18 or at that time the toxicology. So people with 19 greater expertise than I, and with specific 20 management responsibility in those areas, were 21 certainly responsible for the content of those 22 portions of the document. 23 I would say that I had 24 more responsibility primarily for the clinical 75 1 trial portion, which was the limit of my 2 responsibility at Lilly at that time, and for 3 some -- through regulatory, some assurance that in 4 fact had met the required specifications and the 5 regulations and the law. 6 Q Okay, so you were 7 primarily responsible for the clinical trial data 8 that was permitted -- that was presented, the 9 human clinical trial data, and the regulatory 10 data? 11 A Yes, sir, but I think a 12 whole group of us read other parts and made 13 comments about other parts and tried to make sure 14 that the document as a whole made sense and 15 referenced back and forth from the various 16 portions. 17 Q But as far as the 18 responsibility that you felt you had, you were 19 primarily interested in the clinical trial data? 20 A I would have felt that I 21 had not done my job properly had there been errors 22 in other portions which I could have easily 23 detected. 24 Q But you relied on people 76 1 with more expertise in those areas to make a final 2 analysis of that, correct? 3 A Yes, sir. 4 Q But you relied on 5 yourself for the clinical trial data? 6 A Oh, no, there were many 7 other people who had much greater expertise than I 8 in this specific area who were primarily 9 responsible for writing the words and proofreading 10 it and doing the quality control; but again, I 11 shared some responsibility for reviewing the 12 document and adding what I could to the overall 13 review. 14 Q But clinical trials were 15 under your purview, were they not? 16 A Well, remember, most of 17 the clinical trials were in fact done, and I think 18 virtually all of them in the NDA had been at least 19 put in place before I joined Lilly. At the time I 20 joined Lilly, however, I did become responsible 21 for the phase two and three operation, and later, 22 as I assumed responsibility for regulatory, I 23 became responsible for the regulatory piece as 24 well. So although I wasn't responsible for 77 1 designing, I don't believe any of the trials that 2 were in the original New Drug Application, I was 3 responsible for the psychiatrists and other 4 scientists who in fact were responsible directly 5 for those trials and writing up the results. 6 Q That's where I wanted to 7 get was, if it's accurate, is that you were 8 responsible for the psychiatrists who were 9 actually responsible for getting this clinical 10 trial work actually done, is that right? 11 A At least for some of 12 them, yes. 13 Q Well, Doctor Zerbe? 14 A Doctor Zerbe I don't 15 believe is a psychiatrist, as usually defined. 16 Q Well, Doctor Zerbe worked 17 on Prozac extensively. 18 A I don't believe Doctor 19 Zerbe had a great deal of responsibility before 20 the submission of the original New Drug 21 Application. 22 Q Well, later he did, 23 didn't he? 24 A Yes, sir. 78 1 Q Okay, so after the NDA 2 was submitted, how did your role vis-a-vis Prozac, 3 fluoxetine hydrochloride, evolve? 4 A Well, as I have described 5 to you, I was initially responsible for the phase 6 two and three research in the United States, and 7 then other pieces were gradually added to my 8 responsibilities, so eventually I became 9 responsible for phase one research in the Lilly 10 Clinic, I became responsible for phase four 11 research, I became responsible for actually some 12 international research eventually. So throughout 13 the period until I took my current job, I have 14 largely had a responsibility within management for 15 a lot of the clinical trial activity with Prozac 16 gradually expanding, and then eventually even 17 other components of the research laboratories' 18 work on Prozac. 19 Q Do you know of anybody 20 that was more responsible for the clinical trials 21 on Prozac than you were, sir? 22 A Yes, sir. I was in a 23 chain of command, and I've already described the 24 people to whom I reported who had broader 79 1 responsibility than I, and there certainly were 2 people that reported to me that had more direct 3 responsibility and greater expertise specifically 4 related to those trials. 5 Q Well, I've seen a lot -- 6 a lot of documents authored by you, Doctor 7 Thompson, where it appears to me, and others, and 8 others have testified, that Prozac is really -- 9 was really your responsibility ultimately for a 10 period of time. 11 A Well, in the Lilly 12 system, I think it's difficult to say ultimate 13 responsibility because at all times I was 14 reporting to people who clearly were in fact 15 giving me orders and suggestions about Prozac, 16 just as I was making suggestions to people who 17 reported to me. So I was one part of the chain. 18 I'm not at all denying responsibility for 19 anything, I'm just saying that I certainly was not 20 the individual which had sole responsibility for 21 virtually any aspect of it. 22 Q Well, I've seen memos 23 from you where you're addressing maybe fifty 24 individuals, complementing those individuals on 80 1 the work they did in connection with Prozac. 2 A I think we have 3 exceptionally good people and clearly one of the 4 jobs of a leader is to make sure that those people 5 understand both the good and the bad things that 6 they do, and I try to do that job as best I can. 7 Q Well, did you consider -- 8 did you consider yourself a leader in connection 9 with the development and marketing of Prozac? 10 A Well, after the time I 11 came to Lilly, that was one of the products for 12 which I had responsibility. I had no more 13 responsibility for Prozac, nor any less 14 responsibility, than other drugs at comparable 15 phases of development, but obviously this was an 16 extremely exciting drug from the biology of it and 17 the medical effects of it, and so a fair 18 proportion of my time was spent looking at the 19 science and providing whatever advice I could. 20 Q Do you know of any drug, 21 any of Lilly's products to which you've devoted 22 more time, Doctor Thompson? 23 A Well, at certain times, 24 for sure. I mean, there were periods during which 81 1 I spent a great deal more time on other drugs than 2 Prozac. 3 Q Of all the drugs that 4 you've spent time on, have you spent more time 5 total on any other drug than Prozac, Doctor 6 Thompson? 7 A No, I don't think so. 8 Q Have you spent as much 9 time on any of the other drugs as you've spent on 10 Prozac? 11 A Well, again, there were 12 certain periods where I -- 13 Q I'm not talking about 14 certain periods, I'm talking about -- 15 A You're talking about the 16 totality of my employment. 17 Q I'm talking about the 18 totality of your employment, and certainly Prozac 19 was underway when you went to work for Lilly and 20 continues to be a marketed product. 21 A No, I think if you look 22 at all of the indications for it and the vast 23 breadth of clinical trials that we've performed, I 24 probably have spent more of my time on that than 82 1 any other single product. 2 Q Has there been any 3 particular issue that you've devoted more of your 4 time to since you left as executive vice president 5 of Lilly Research Labs than issues raised by 6 Prozac? 7 MR. FREEMAN: Could you 8 restate that, Paul? 9 MR. SMITH: Read it back, 10 please. 11 REPORTER: (READING) 12 Question: Has there been any particular issue 13 that you've devoted more of your time to since you 14 left as executive vice president of Lilly Research 15 Labs than issues raised by Prozac? 16 MR. FREEMAN: I don't 17 comprehend the question, but that's not to say 18 that the witness might understand it, but I don't 19 understand it. 20 A Since the time I took my 21 present position, I haven't spent very much of my 22 time on Prozac, and there are a lot of other 23 issues that have occupied far more of my time in 24 this position. 83 1 Q That's why I intended at 2 least to direct my question to up to the time you 3 left as executive vice president of Lilly Research 4 Labs. 5 A Yes, sir. Up until that 6 time -- 7 Q Yes. 8 A -- I think we've 9 established that I probably spent more of my 10 energy on Prozac than any other single molecule. 11 Since that time, what I said was that there have 12 been far -- a large number of other things that 13 have taken up much more of my time. 14 Q I understand that, I 15 understand that, but up until you became the chief 16 scientific officer of Eli Lilly and Company, as I 17 understand it, you've not devoted as much time to 18 any other molecule that Lilly -- or product that 19 Lilly had produced than Prozac? 20 A Any other single molecule 21 over the totality of that period, that's correct. 22 Q And any other single 23 issue other than issues raised by Prozac. 24 A No, over the totality of 84 1 that time, you're correct. 2 MR. SMITH: We've changed 3 our procedure, we've got books, we've got -- 4 MR. FREEMAN: I'm glad to 5 see it. 6 Q (BY MR. SMITH) Do you 7 consider -- have you ever considered that Prozac 8 is Lilly's most important drug? 9 A No. 10 Q Have you ever considered 11 that Prozac is the most significant drug that 12 Lilly produces? 13 A Well, of course the 14 discovery of Prozac antedated my coming to Lilly, 15 but I would say that of the drugs that we have 16 marketed since I came to Lilly, I think that's the 17 most significant one. 18 Q You think Prozac is the 19 most vital drug to Eli Lilly and Company's 20 well-being? 21 A I don't understand vital 22 and well-being. 23 Q Vital to its financial 24 well-being. 85 1 A Oh, financial. Well, I 2 think that worldwide sales of Ceclor are very 3 close to worldwide sales of Prozac, but either of 4 those products represent only a relatively small 5 fraction of total sales of the corporation. We're 6 a fairly diversified corporation. 7 (THOMPSON EXHIBIT NO. 1 MARKED FOR 8 IDENTIFICATION.) 9 THE WITNESS: Yes, sir. 10 Q (BY MR. SMITH) Exhibit 1 11 is a document authored by you, is it not? 12 A Yes, sir. 13 Q Dated February 7th, 1990, 14 correct? 15 A Yes, sir. 16 Q It's directed to various 17 high ranking individuals at Eli Lilly, or at Lilly 18 Research Labs, is it not? 19 A Yes, sir. 20 Q All of whom are 21 individuals who report to you in some form or the 22 other -- or reported to you in some form or the 23 other on February 7th, 1990, correct? 24 A I don't remember whether 86 1 Doctor Weinstein and Doctor Keohane reported to me 2 at that time or not, but they did at one time. 3 Q Either directly or 4 indirectly in February 1990? 5 A Well, reported to has a 6 specific connotation at Lilly, which would be a 7 direct report. 8 Q All right. You had the 9 authority to write these gentlemen and expected 10 that they would respect your judgment on matters, 11 did you not? 12 A Yes. 13 Q Have you seen this 14 document in preparation for this deposition, 15 Doctor Thompson? 16 MR. FREEMAN: You can 17 answer it. 18 A Yes, sir. 19 Q And is there anything 20 inaccurate or incorrect about this document that 21 you've authored? 22 A Not that I'm aware of. 23 Q The document says: I 24 wish to reemphasize the messages from Bob Zerbe 87 1 and Max Talbott in regards -- in this regard in 2 terms of the resource needs to stay absolutely on 3 top of every Prozac adverse event report. 4 Anything that happens in the UK can threaten this 5 drug in the US and worldwide. We are now 6 expending enormous efforts fending off attacks 7 because of, one, relationships to murder, and two, 8 inducing suicidal ideation. The appropriate level 9 of response is indicated by Dan Masica himself and 10 Charles Beasley immediately flying to Boston to 11 talk to the authors of the paper on suicidal 12 ideation. We have numerous foes such as the 13 Church of Scientology. The FDA is very, very 14 skitterish. I have talked with Paul Leber twice 15 in the last several days, exclamation mark. We 16 must not allow one day to elapse on follow-up, 17 flying to, investigating, et cetera, everything 18 about Prozac. Bob Zerbe can correct me for a wild 19 guess, but I think we have twenty full-time 20 equivalents at least working just on Prozac 21 postmarketing safety and support and if necessary 22 we will stop everything else going on to provide 23 more. Every significant event about Prozac has 24 been a show stopper with the twelfth floor 88 1 meetings immediately with Earl, Mel, et cetera. 2 There cannot be a fumble of even minor proportions 3 on this one because political pressure and 4 perceptions and public news, not science, could 5 cause us to lose this one, five exclamation marks, 6 end quote, signed Leigh, correct? 7 A Well, you made four 8 errors in reading it, but the substance of what 9 you said is correct. I don't see any quotation 10 marks. 11 Q Well, I was putting it in 12 quotes for purposes of the record so that we would 13 know what I said is not what you said, but that it 14 was what you said, correct? 15 A If you say so, sir. 16 Q Was there ever a fumble 17 of even minor proportions in connection with 18 Prozac, Doctor Thompson? 19 A No, sir. 20 Q What is the twelfth 21 floor? 22 A It's the floor on which 23 the most senior executives at Lilly have their 24 offices. 89 1 Q Do you office there now, 2 sir? 3 A Now I do. 4 Q Did you then? 5 A No, sir. 6 Q Where did you office 7 then? 8 A I think at this time I 9 was in the first floor of Building 28. 10 Q But you had a lot of 11 meetings on the twelfth floor, did you not? 12 A Yes, sir. 13 Q That's where your bosses 14 resided, didn't they? 15 A Doctor Perelman was 16 there, yes, sir. 17 Q Did you perceive a threat 18 to Prozac? 19 A Yes, sir. 20 Q You used the term here, 21 it is your term, "the FDA is very, very 22 skitterish," correct? 23 A Yes, sir. 24 Q What were they skitterish 90 1 about at that time, in February 1990? 2 A Whenever there are many 3 news reports about a drug, and I believe either 4 positively or negatively, the FDA becomes very 5 concerned because they, like Lilly, believe that 6 fact information about drugs should be delivered 7 to health professionals, and so a great deal of 8 news, again either good or bad, can make the FDA 9 concerned to make sure that they know all about 10 the drug and that they are ahead of the news media 11 and any reports. 12 Q Well, the news was bad at 13 that time, wasn't it; there was attacks linking 14 Prozac to murder and suicidal ideation, wasn't 15 there? 16 A There were also very good 17 reports in the news as well. 18 Q But there were bad 19 reports is what you're referring to, wasn't it? 20 A No, I think actually we 21 were as much concerned about the good reports as 22 we were about the bad reports. 23 Q This appears to me that 24 you're frantic, Doctor Thompson, in directing this 91 1 memo; is that not correct? 2 A I haven't ever, that I 3 recall, been accused of being frantic in my 4 professional career, but if you wish to use that 5 term. 6 Q Is that not an accurate 7 term with respect to your feelings on February 7, 8 1990, in connection with this situation, Doctor 9 Thompson? 10 A I don't think frantic is 11 a word that I would use. 12 Q What word with you use 13 concerned? 14 A I was very concerned 15 because we had far more ability to support Prozac 16 in investigating all aspects of its news 17 reporting, adverse events and so forth in the 18 United States than we did in some of our 19 affiliates that had very small staffs, and the 20 purpose of this memo was to emphasize to one of 21 those affiliates that in fact this was a very 22 important issue, and although they had a small 23 staff and they had very many things to do, this 24 was a very, very important issue. 92 1 Q The issue of Prozac and 2 its relationship to murder and its inducing 3 suicidal ideation is the subject that you've 4 mentioned in this memo, is it not? 5 A Yes, but I think the 6 purpose of the memo, if you read the first 7 sentence, was actually to be on top of every 8 Prozac adverse event, which has always been an 9 extremely important issue at Lilly with every one 10 of our products. 11 Q All right. Well, was the 12 FDA very, very skitterish about the adverse events 13 in connection with Prozac at that time? 14 A Yes, sir. 15 Q Was there a problem with 16 the adverse events that were being reported in 17 connection with Prozac and murder and suicidal 18 ideation at that time? 19 A Well, I think we need to 20 distinguish between the scientific adverse event 21 reporting, which I do not believe there was a 22 problem, and the news reports that got 23 incorporated as adverse events, which I think were 24 the cause of the problem. 93 1 Q So you didn't see any 2 problem with the, say, actual 1639's that were 3 being submitted to the Food and Drug 4 Administration in connection with homicidal acts 5 and suicidal -- suicidal ideation and suicidal 6 acts? 7 A Well, we're always 8 vitally concerned about any report of an adverse 9 event on any of our Lilly drugs, but the specific 10 subject of the memo and the reason I used the word 11 skitterish at the FDA was, in my opinion, as best 12 I can recall, not the adverse event reports that 13 we were filing, but in fact the high volume of lay 14 press publication on the drug. 15 Q Well, had you talked to 16 the FDA about these reports in the press? 17 A Yes, sir. 18 Q You say here, "I've 19 talked with Paul Leber twice in the last several 20 days," exclamation mark, correct? 21 A Yes, sir. 22 Q Now, who is Paul Leber? 23 A Paul Leber is Director of 24 the Neuropsychiatric Drugs Division of the Food 94 1 and Drug Administration. 2 Q And what was the subject 3 of the two conversations that you had with him in 4 the last several days? 5 A I can't remember the 6 specific details, but I think they were related 7 to, in fact, the press reports at that time. 8 Q You see, I don't see the 9 word press reports -- the words press reports at 10 all in this exhibit, Doctor Thompson. Do you? 11 A No, I don't see those 12 words. 13 Q And I don't -- it seems 14 to me that you're talking about postmarketing 15 events and reporting postmarketing events. Isn't 16 that the subject of this memo? 17 A Well, I think these were 18 events that occurred after marketing for sure, and 19 as Lilly is very conservative in how we handle 20 adverse event reports, we would report things that 21 appear in the lay press as being adverse events 22 even with no additional information about them. 23 Q Well, you say -- talking 24 about "the resource needs to stay absolutely on 95 1 top of every Prozac adverse event report." 2 A Yes, sir. 3 Q How long had you known 4 Paul Leber as of February 7th, 1990? 5 A Oh, I think I may have 6 met him at scientific meetings a year or two 7 before that, something like that. 8 Q You've just known him 9 since 1988? 10 A Well, no, it must have 11 antedated that, but I certainly can't ever recall 12 meeting him before I came to Lilly, and I can't 13 recall when I first actually met him, but he and I 14 would both be attending scientific meetings and 15 clinical pharmacology meetings. 16 Q Has Paul Leber been in 17 your home, Doctor Thompson? 18 A No, sir. 19 Q Have you been in his? 20 A No, sir. 21 Q Have you and he been out 22 together socially? 23 A No, sir. 24 Q You've not had dinner 96 1 together, or a meal together, anywhere at any 2 time? 3 A No, sir, I don't believe 4 so. 5 Q Have you had dinner or a 6 meal with any member of the United States Food and 7 Drug Administration that you recall? 8 A Yes, sir. 9 Q Who? 10 A I recall that one of the 11 reviewers in the endocrine division and I had a 12 business lunch once in Rockville. I recall being 13 at medical meetings at which things like 14 receptions and either lunch or dinner were part of 15 the business meeting where Doctor Temple and I 16 attended. Doctor Faich and I from the FDA were 17 at -- again, similar things, business lunch or 18 dinners that were sponsored by organizations that 19 we were both attending. 20 Q Well, you didn't have any 21 problem, as far as you're concerned, calling Paul 22 Leber and talking to him on the telephone in 23 February of 1990, did you? 24 A Problems, sir? 97 1 Q You didn't have any 2 problem talking to him on the phone? 3 A He called me and I called 4 him, that's -- 5 Q You each -- you each felt 6 comfortable calling each other and talking to each 7 other on the phone? 8 A Yes, sir. 9 Q Even though he's with the 10 regulatory agency and you're with a pharmaceutical 11 firm manufacturing products that had to be 12 approved by that regulatory agency? 13 A I don't understand 14 problem. I mean, that's the way business is 15 conducted. 16 Q All right. Did Paul 17 Leber have any ideas concerning the safety of 18 Prozac at that time? 19 A Let's see, this was -- 20 Q February 1990. 21 A This was after the 22 advisory committee meeting, so I would say Doctor 23 Leber had some very firm ideas about Prozac at the 24 time of the Advisory Committee meeting for sure. 98 1 This is also -- 2 Q No, it's not after the 3 advisory committee meeting, the advisory committee 4 meeting was in September 1991. 5 A No, I think the advisory 6 committee meeting was about a year and three 7 months before the initial approval. 8 Q Well, I'm talking 9 about -- you're talking about the preapproval 10 advisory committee meeting? 11 A Yes, sir. 12 Q You're not talking about 13 the advisory committee meeting conducted to 14 examine the issue of Prozac and suicidality? 15 A Well, the advisory -- 16 right, the preapproval advisory committee where 17 Doctor Leber attacked me and I attacked him was 18 largely done a year before the approval, and both 19 of us, I think, had very firm opinions about the 20 drug and each other at that time. 21 Q You all had an attack, he 22 attacked you and you attacked him? 23 A I think if you reviewed 24 the videotape of the transcript of that meeting, 99 1 you'd have to come to something close to that 2 word. 3 Q Was it physical? 4 A Oh, no, sir. 5 Q Well, did Paul Leber, in 6 your judgment, have an opinion in February 1990 7 concerning the safety and efficacy of Prozac in 8 connection with the issue of suicidal ideation and 9 murder, as is mentioned in this exhibit? 10 A Yes, sir. I think he was 11 very concerned, as we were at that time, that we 12 were -- both groups, both the FDA, and not just 13 Doctor Leber, but his whole division and others 14 there, and all of us that were involved at Lilly 15 were struggling to find out what the scientific 16 truth was and to get as much detail as we could. 17 Q Well, did you have an 18 opinion on whether or not Prozac could -- had any 19 relationship to murder in February of 1990? 20 A Yes, sir. 21 Q And what was that 22 opinion, sir? 23 A Well, my opinion, of 24 course, changed over time, or at least it evolved 100 1 over time as more and more information was 2 available, but I'm sure that -- 3 Q I'm talking about 4 February 1990. 5 A Well, I can't remember 6 specifically the dates, sir. I don't -- I never 7 felt that we had any substantive evidence that 8 Prozac was related to murder, but I was obviously 9 very deeply concerned, as were other people at 10 Lilly, in making sure that we understood 11 everything possible about these reports, to make 12 sure that in fact we didn't have a problem. 13 Q How about suicidal 14 ideation? 15 A Well, again, I never 16 felt, as I can recall at any of these times, that 17 the preponderance of the scientific evidence would 18 causally link suicidal ideation with the drug. 19 But again, we were vitally concerned with this, as 20 we were with rash and every other adverse event 21 that had been reported during the development and 22 marketing of Prozac. 23 Q Did rash become a show 24 stopper on the twelfth floor -- 101 1 A Yes, sir. 2 Q -- as you mentioned here? 3 A Yes, sir. Not at this 4 time, but earlier on. 5 Q It was a show stopper on 6 the twelfth floor? 7 A It was our primary 8 medical concern at the time that we submitted the 9 New Drug Application, and we were extremely 10 concerned about it. 11 Q All right. Is rash 12 associated with Prozac? 13 A I don't honestly know at 14 this stage because looking now at very, very many 15 patients, there is very little evidence that 16 there's more people that would get a rash on 17 Prozac than on taking any other drug or placebo. 18 However, at the time that we submitted the New 19 Drug Application, there was about a one percent 20 greater incidence of rash in people on Prozac as 21 on comparators, and we had -- 22 Q How about placebo? 23 A Again, about one percent 24 more than on placebo, but we had two cases that 102 1 concerned us a great deal that could have, in 2 fact, indicated that the drug might induce a very 3 severe or virtually life-threatening rash, and 4 that was our major concern. 5 Q Only two cases of a rash 6 reported in the clinical trials -- 7 A No, sir -- 8 Q -- caused you concern? 9 A -- there were more cases 10 than that, but I recall two that were severe 11 enough that we were concerned that other people 12 might have similar kinds of events. 13 Q So in that instance, in 14 the instance of rash, two severe cases of rash 15 raised concern on your part? 16 A Yes, sir. Overall we 17 had, as I best recall, about a four percent 18 incidence of patients on Prozac and about a three 19 percent incidence in the control groups, and a 20 difference of one percent -- certainly with more 21 data, that difference has narrowed, so the 22 instance is about the same. But again, we had two 23 patients that I recall very distinctly spending a 24 lot of time studying those cases that we were very 103 1 concerned that our marketing the drug widely, 2 there might be more such events, and because one 3 of them progressed while the lady was taking 4 Prozac, we were very much concerned about exactly 5 how we would advise physicians to manage a patient 6 who developed a rash on the drug. 7 Q Was this concern because 8 of the -- I don't understand for sure, was this 9 concern about rash because of the two patients or 10 the one percent difference in placebo versus 11 Prozac that occurred during the clinical trials? 12 A Well, I think both of 13 those factors, one is we didn't have enough 14 patients to know whether a one percent difference 15 in fact indicated that the drug was likely to 16 cause more rash than you would see with any other 17 drug, but the reason we were concerned -- had all 18 of those cases of the four percent been relatively 19 trivial rashes that went away when the drug was 20 continued, I don't think we would have had the 21 level of concern that was raised by two patients, 22 who although they had quite different rashes, one 23 of them, an elderly lady clearly had progression 24 of her illness while she was continued on the 104 1 drug. And this is a very significant point 2 because since something in the range of three or 3 four percent of people taking any drug will 4 develop a rash, you would want to specifically 5 warn physicians, say if you see a rash with this 6 drug, you better think about stopping the drug 7 because it could be you're seeing the beginning of 8 something that could get bad rather then just a 9 nonspecific kind of rash that you see with 10 anything. 11 Q Even a one percent 12 difference in the clinical trials of fluoxetine 13 versus placebo would be sufficient to raise that 14 in your mind? 15 A Coupled with the fact 16 that one of the patients had something that 17 actually required hospitalization and we were 18 concerned that it was a syndrome that could be 19 even worse in other patients, and a second patient 20 had erythema multiforme, which although not 21 life-threatening in that patient, is part of a 22 syndrome that can be life-threatening. 23 So again, if all of the 24 patients had just had a nonspecific mild rash that 105 1 didn't require a particular therapy and went away, 2 a one percent difference I don't think would have 3 raised a great deal of concern. That's why I 4 pointed to those two cases as being of specific 5 concern, coupled with the one percent difference, 6 we didn't know whether this was related to Prozac 7 or not. 8 Q Well, rash is still 9 listed as an adverse event reported more 10 frequently on Prozac than placebo, is it not? 11 A I don't think the label 12 has been changed, but I think the preponderance of 13 evidence from ongoing trials would suggest that 14 the incidence of rash now is about the same on 15 Prozac or comparator drugs. 16 Q But the PDR, the label is 17 the same, the adverse event is attributed more 18 often in -- rash is attributed more often in 19 Prozac patients than placebo patients? 20 A If you say so. I haven't 21 reviewed the label recently, but once a negative 22 statement finds its way into a label, it is very 23 rarely ever removed. 24 Q It's hard to get rid of 106 1 negative statements? 2 A It's not a common 3 practice that those are changed. 4 Q You say in Exhibit 1 that 5 anything that happens in the UK can threaten this 6 drug in the US and worldwide, correct? 7 A Yes, sir. 8 Q Expand on that for me; 9 what could have happened in England that would 10 have threatened Prozac in the United States and 11 throughout the world? 12 A If we had either gotten a 13 flurry of lay press reports that were very 14 concerning, or a series of significant adverse 15 events, it could have led to the company 16 withdrawing the drug in other markets, it could 17 have led to regulatory authorities withdrawing the 18 drug in other markets. 19 Q And this would have been 20 disastrous to Lilly? 21 A Well, we thought this 22 drug was saving a lot of lives and in fact was a 23 very, very major advance in managing patients, so 24 if in fact the drug weren't available to those 107 1 patients, I would have called that a medical 2 disaster, yes, indeed. 3 Q I didn't say that; I said 4 this would have been disastrous to Lilly, correct, 5 if the drug had been withdrawn from the market? 6 A Well, I don't want to 7 quibble over the word disastrous. We've withdrawn 8 other products because of concerns of safety and 9 done other things which financially caused the 10 company a great deal of pain in acting in our 11 usual conservative fashion, but it certainly 12 wouldn't have been good financially, it wouldn't 13 have been good for the reputation of the company, 14 but primarily the concern of the people that I was 15 talking with every day was that in fact it would 16 deny a population of patients a new and extremely 17 effective therapy. At this time, I don't think 18 there was another serotonin selective uptake 19 antagonist available to those patients. 20 Q Well, did you have the 21 opinion that Lilly could go down the tube if you 22 lost Prozac? 23 A I don't think it would 24 have been good for the company; I doubt that the 108 1 existence of the company would have been at risk. 2 Q Well, let me show you 3 Exhibit 2. 4 (THOMPSON EXHIBIT NO. 2 MARKED FOR 5 IDENTIFICATION.) 6 A Yes, sir, I used the word 7 go down the tubes. 8 Q Exhibit 2 is another 9 document that you authored, is it not, Doctor 10 Thompson? 11 A Yes, sir. 12 Q In fact you authored 13 Exhibit 2 two minutes after you authored Exhibit 14 1, didn't you? 15 A Yes, sir. 16 Q And there you say: I'm 17 concerned about reports I get re UK attitude 18 toward Prozac safety. Leber suggested a few 19 minutes ago we using the CSM database to compare 20 Prozac aggression and suicidal ideation with other 21 antidepressants in the UK. Although he is a fan 22 of Prozac and believes a lot of this is garbage, 23 he is clearly a political creature and will have 24 to respond to the pressures. I hope Patrick 109 1 realizes that Lilly can go down the tube if we 2 lose Prozac and just one event in the UK can cost 3 us that. You know my prejudice about Patrick, but 4 if I hear one more problem about not covering 5 Prozac safety in the UK, Allan, I'm going to 6 really be up in arms, period, Leigh, end quote, 7 correct? 8 A Yes, sir. 9 Q Did I make any mistakes 10 in reading that? 11 A Only one. 12 Q Okay, I'm getting 13 better. Have you seen that document before? 14 A Yes, sir, I authored it. 15 Q Have you seen it in 16 preparation for your deposition, sir? 17 MR. FREEMAN: You can 18 answer. 19 A I think so, but I'm not a 20 hundred percent sure. 21 Q You did feel, in February 22 of 1970 (sic), that Lilly could down the tube if 23 Lilly lost Prozac, didn't you, Doctor Thompson? 24 A Well, what I said was I 110 1 hoped that Patrick realizes that Lilly can go down 2 the tube, and like you, I sometimes exaggerate to 3 make a point. 4 MS. ZETTLER: I object to 5 that response. 6 MR. SMITH: Yes, I object 7 to the response as being nonresponsive and a side 8 bar remark, if a witness can make a side bar 9 remark. 10 MR. FREEMAN: Continue, 11 please. 12 MR. SMITH: Can they? 13 Q (BY MR. SMITH) I didn't 14 hear exactly what you said, but let me ask it 15 again: Did you believe on February 7, 1990 that 16 Lilly could down the tubes if you lost Prozac? 17 A Well, I don't think I 18 believed that the company would go out of 19 business. I do believe that it would have been a 20 severe, both medical scientific as well as 21 financial, blow to the company. 22 Q Why did you write that if 23 you didn't believe it, Doctor Thompson? 24 A Because I wanted to 111 1 emphasize the importance that the UK affiliate, 2 which as I explained was short staffed, it didn't 3 have the staff that we had in the US, needed to 4 regard each of those reports as very important, 5 even though from their perspective in the UK 6 alone, they did not necessarily perceive this to 7 be a worldwide issue. 8 Q I don't see anything in 9 this memo, Exhibit 2, about the UK having a small 10 staff. 11 A Well, I think if you 12 refer back to Exhibit No. 1, you can certainly see 13 that flavor in the sense that we had a large 14 number of people who could, in fact, be applied to 15 this task if you recall in that memo. 16 Q I don't see there 17 anything -- any comment there about the United 18 Kingdom having a small staff, do you? 19 A Well, I was trying to 20 explain to you, as you asked, the background for 21 the memo, and if you read the sentence, "Bob Zerbe 22 can correct me, but I would think we have twenty 23 full-time equivalents at least working just on the 24 postmarketing safety," that was certainly a much 112 1 larger number than the staff that was available 2 within the UK, and that was the point of my 3 concern. 4 Q Well, the point of your 5 concern is that -- it appears to me, that if we 6 don't stay on top of Prozac safety in the UK, 7 there can be a problem that could cause Lilly to 8 go down the tube if Prozac is lost, correct? 9 A Yes, sir. 10 Q You say here that Paul 11 Leber is a fan of Prozac -- 12 A Yes, sir. 13 Q -- is that correct? Do 14 you know how long he had been a fan of Prozac? 15 A Well, at least since the 16 time of approval of the drug, he had felt that it 17 was, in fact, a very major advance in the 18 treatment of depression and -- 19 Q Did he tell you that? 20 A Yes, sir. 21 Q When did he first tell 22 you that? 23 A I can't remember exactly, 24 but it was somewhere after we submitted the safety 113 1 update and somewhere in the timing of the final 2 approval by the FDA of the original NDA. 3 Q Did you ever discuss 4 prior to February 7th, 1990 the issue of whether 5 or not Prozac could cause suicidal ideation or 6 influence suicidal behavior in any way? 7 A Yes, sir. I think the 8 conversations were before 1990. 9 Q Specifically regarding 10 suicide and Prozac's relation to suicide? 11 A We were very much 12 concerned throughout about the treatment of the 13 disease depression, which of course includes 14 suicide and suicidal ideation as part of its 15 manifestations, and therefore, with any 16 antidepressant, one is always concerned in 17 providing the best information possible about how 18 the physician should evaluate and treat a patient 19 who has depression who is at very high risk for 20 both suicide and suicidal ideation. So, this has 21 been a part of discussion from the first time we 22 started talking about what kind of generic 23 warnings to put in the label for this 24 antidepressant compared to others, because we had 114 1 pretty good evidence early on that this drug would 2 be much safer in overdose than the other 3 antidepressants. 4 MR. SMITH: I move to 5 strike the answer as not responsive to the 6 question I asked. 7 Q My question is: Did you 8 talk with Doctor Leber, the head of the Department 9 of neuropharmacology at the Food and Drug 10 Administration, concerning whether or not Prozac 11 caused suicide or had any relationship to suicide 12 before February 7th, 1990? 13 A Well, I certainly did 14 after the appearance of the article authored by 15 Doctor Teicher, which I believe antedated this 16 date by about two years. That's roughly -- but 17 I'm not sure of those dates. 18 Q No, it didn't. It was 19 published in February 1990, Doctor Thompson. 20 A Well, I know for sure 21 that we had conversations about that article at 22 the time that it was published. 23 Q Before it was published, 24 didn't you? 115 1 A Well, I don't recall 2 conversations with Doctor Leber before the 3 publication itself related to any causal 4 relationship between Prozac and suicidal ideation 5 or suicidality. 6 Q All right. No 7 discussions with Paul Leber concerning any causal 8 relationship between Prozac and suicidality before 9 the publication of the Teicher article in February 10 of 1990? 11 A I don't think so; I can't 12 recall specifically. 13 Q You see, the Teicher 14 article was published in February 1990, correct? 15 A If you say so. 16 Q You were -- you mentioned 17 in Exhibit 1 that some of your scientists had even 18 gone to Boston and flown up there and talked to 19 Teicher about his article, don't you? 20 A I don't recall Doctor 21 Teicher's name, but that was probably the event 22 that they had flown to -- yes, the authors of 23 paper on suicidal ideation, that must be it, 24 because others of our people would fly to places 116 1 to work up other adverse event reports, but I 2 think that one does refer to Doctor Teicher. 3 Q Did you ever have any 4 conversations before this with Doctor Paul Leber 5 at the FDA concerning an association of Prozac and 6 violent -- and aggressive behavior? 7 MR. FREEMAN: Are you 8 using association as causal? 9 MR. SMITH: Causal 10 association. 11 A I don't recall any, sir; 12 but again, I'm not explicit on the dates because 13 there's a whole lot of events that occurred over a 14 continuum. So, not to my knowledge, no. 15 Q Well, were you talking to 16 Paul Leber continuously over a period of time? 17 A Not continuously, but I 18 would say that we had a number of conversations, 19 especially after he had given us instructions for 20 preparing the safety update. 21 Q In looking at Exhibit 2, 22 I get the impression that you're frantic; is that 23 correct? 24 A I don't again recall 117 1 people ever using that word in relation to my 2 behavior or attitudes in any of my professional 3 career. 4 Q Well, did you feel 5 frantic, whether anybody ever used that term with 6 you? 7 A I wanted to make sure 8 that all of our foreign affiliates recognized the 9 importance of a global basis of any adverse event, 10 especially of this drug because of the lay press 11 reports, and my concern was that often foreign 12 affiliates have a more limited view of things as 13 to how it would impact them in their own market. 14 Q Simply, were you frantic? 15 A I was not frantic. 16 MR. SMITH: We've got to 17 change the tape. 18 (SHORT BREAK TAKEN.) 19 (THOMPSON EXHIBIT NO. 3 MARKED FOR 20 IDENTIFICATION.) 21 MR. BOUR: This is the 22 start of Tape No. 2, the time is 11:39. 23 Q (BY MR. SMITH) Doctor 24 Thompson, take a minute to review Exhibit No. 3 118 1 and let me ask you some questions about it, 2 please, sir. 3 A Yes, sir. 4 Q Exhibit No. 3 is a 5 document dated April 15, 1991 and has to do with 6 upcoming TV appearances, correct? 7 A Yes, sir. 8 Q It's directed to you from 9 Mr. Mitch Daniels, correct? 10 A Yes, sir. 11 Q Mr. Mitch Daniels' 12 position with Eli Lilly and Company at that time 13 was what, sir? 14 A I think he was vice 15 president of the corporation with the specific 16 responsibility for -- I'm not sure of the exact 17 words, but public and professional and political 18 relationships. 19 Q He was a PR man, correct? 20 A I wouldn't use that term, 21 but yes, he was responsible for our public 22 appearances. 23 Q He was a lobbyist for 24 Lilly in Washington, was he not? 119 1 A Part of his 2 responsibilities would include lobbying for Lilly, 3 yes. 4 Q And who is Mr. E.A. West? 5 A Ed West was then director 6 primarily of public relations, contacts with the 7 media primarily. 8 Q He says -- Mr. Daniels 9 says in the document, "Thanks for taking time from 10 Friday's practice session." Do you see that? 11 A Yes, sir. 12 Q You had a practice 13 session? 14 A Yes, sir. 15 Q Who was there at this 16 practice session? 17 A Well, I think Mitch was 18 there; I'm not sure who else within Lilly was 19 present. I think they brought in two people who 20 were coaches to teach you how to handle 21 interviews. 22 Q Two outside consultants? 23 A Yes, sir, as I recall. 24 Q Who were specialists in 120 1 how to appear on a talk show or how to do an 2 interview with a reporter? 3 A Yes, sir. 4 Q And you participated in 5 that? 6 A Yes, sir. 7 Q And they coached you on 8 how to do interviews and how to talk with 9 reporters? 10 A Yes, sir. 11 Q Were there any lawyers 12 there at this session? 13 A I don't believe so. 14 Q Then Mr. Daniels wrote 15 down some messages, did he not? 16 A Yes, sir. 17 Q And these are messages 18 that he wanted to make sure that you got across in 19 giving these interviews, correct? 20 A He says, "which I offer 21 to augment your own thoughts." 22 Q All right. So, he had 23 some ideas concerning his thoughts about what you 24 should get across in the interviews, correct? 121 1 A He's offering me his 2 thoughts to augment my own, yes. 3 Q Do you recall what 4 thoughts you had then? 5 A Oh, surely, I had a whole 6 numbers of thoughts because, after all, I had been 7 reviewing all of the scientific data and so forth. 8 Q You had a goal -- or he 9 suggested three goals, did he not? 10 A Well, three goals with 11 some subpoints under each, yes, sir. 12 Q Then he also had some 13 instruction for you or information for you 14 concerning tone, did he not? 15 A Yes, sir. 16 Q He says, "We hope the 17 overall impression left by your demeanor and word 18 choice will be that of the caring physician," 19 correct? 20 A Yes, sir. 21 Q You would show 22 compassion? 23 A Yes, sir. 24 Q You must constantly place 122 1 yourself, and therefore Lilly, on the patient's 2 side, he suggests, does he not? 3 A Yes, sir. 4 Q Then he suggests that you 5 use medical authority, statistics and factual 6 references, lines like as a physician and back in 7 medical school all help, but very importantly, you 8 must seize opportunities in a polite but firm 9 manner to expose and correct untruths, correct? 10 A Yes, sir. 11 Q Do you feel like you've 12 done that so far this morning? 13 A I hope so. 14 Q He suggests that you be 15 friendly, right? 16 A Yes, sir. 17 Q He says it comes 18 naturally, just remind yourself, correct? 19 A Yes, sir. 20 Q This has sort of been the 21 corporate line, has it not, in connection with 22 these message goals that he suggests? 23 A Well, I don't see -- 24 Q On Page 1. 123 1 A I don't see anything 2 that's incompatible with what the corporation's 3 overall attitude was towards the drug in these 4 interviews. 5 Q How many interviews did 6 you give or have you given in connection with 7 Prozac and the issue of suicide or violent 8 aggressive behavior? 9 A For Prozac -- you mean 10 with the lay press rather than other audiences? 11 Q Let's start with the lay 12 press then. This was for the lay press, was it 13 not? 14 A Yes, sir. 15 Q All right. 16 A Both print, radio and 17 television, probably fifty. 18 Q So you're sort of a media 19 pro, as he says? 20 A No, but Lilly had asked 21 me, at that time, to be its predominant 22 spokesperson as a scientist on camera. 23 Q Well, he says, "But a 24 little practice and message honing is usually 124 1 useful, even for a seasoned media pro like you," 2 does he not? 3 A Yes, sir, that's what he 4 says. 5 Q He considers yourself a 6 media pro? 7 A He was being kind. 8 Q You've given fifty 9 interviews in the written and televised lay press, 10 correct? 11 A And radio, yes, sir. 12 Q And radio. How many 13 scientific issues have you -- scientific meetings 14 have you attended where you've presented papers in 15 connection with these issues presented by Prozac 16 and suicide and violent aggressive behavior? 17 A Well, let's distinguish 18 about presenting papers, because I don't recall 19 that I've authored, as a primary author, hardly 20 any papers on Prozac. However, I've probably 21 given two or three hundred scientific 22 presentations at which Prozac was at least part of 23 the topic being discussed. 24 Q I would like to limit it 125 1 to where the subject of discussion was Prozac and 2 the issue of Prozac and it's relationship to 3 suicide and Prozac and it's relationship to 4 violent aggressive behavior. 5 A Well, that would be a 6 smaller subset, both of the public -- when I said 7 fifty, remember I said Prozac in general, because 8 I would say a much smaller subset of that would 9 relate to those specific issues of Prozac, less 10 than half, and even a smaller fraction of the 11 scientific presentations on Prozac. 12 Q Give me a number. 13 A Of several hundred 14 professional discussions where Prozac was at least 15 a part, I would say that in more than half of them 16 I don't think that subject would come up at all. 17 In fact, I don't recall any professional 18 discussion where that was the primary topic, 19 professional discussion. 20 Q Excluding those 21 discussions you've had with all the consultants 22 that Lilly has employed on the subject. 23 A I'm sorry, sir; I thought 24 you were talking about when I was making a 126 1 presentation to an audience rather than in being 2 part of a group or a part of a discussion or where 3 I was the audience. When I said several hundred, 4 I meant where I would get up in front of a 5 professional audience and be talking about things 6 which would either be predominantly about Prozac 7 or in which that was a major part of the 8 discussion. 9 Q All right. 10 A And what I asserted was 11 that less than half of the time was there any 12 discussion of the issues that you brought up 13 specifically before those professional audiences. 14 Q Okay. How many meetings 15 with consultants have you attended in connection 16 with the issue of Prozac suicidality and violent 17 aggressive behavior? 18 A Specifically related to 19 those two issues -- you mean when that was the 20 predominant topic being discussed? 21 Q Yes. 22 A I think at least two 23 consultant meetings where that was the primary 24 topic of the meeting. 127 1 Q Were there others where 2 it was a secondary topic? 3 A Yes, sir. 4 Q How many? 5 A We've had so many 6 discussions with various experts on issues with 7 Prozac, where something like phospholipidosis 8 might be the primary thing, but we'd be going over 9 all of the data, so that that -- you know, that 10 may well come up as one of the other adverse 11 events. I'd say fifteen or twenty discussing 12 Prozac in general with various experts where at 13 least that would be mentioned. 14 Q Have you ever given your 15 deposition before? 16 A Yes, sir. 17 Q In connection with a 18 pharmaceutical product? 19 A Yes, sir. 20 Q In connection with 21 Prozac? 22 A No, sir. 23 Q In connection with your 24 employment at Lilly? 128 1 A Yes, sir. 2 Q What drugs have you 3 testified concerning since your employment at 4 Lilly? 5 A Related to a Lilly 6 product, and if testify means not a deposition but 7 testifying in court, the answer is none. I have 8 testified in court on cases for which I was a 9 consultant before coming to Lilly, after the time 10 of my employment at Lilly, but I have done a 11 deposition about a Lilly product since coming to 12 Lilly, but not testified. 13 Q When I say the word 14 testify, I'm using it in the technical legal 15 since. You're giving testimony here today -- 16 A I see, sir. 17 Q -- in a deposition, so I 18 want you to include any kind of sworn testimony 19 given. So what would your answer be? 20 A That I have given a 21 deposition about a Lilly product since I've been 22 employed by Lilly, but it wasn't Prozac, and I 23 think it was a vitamin preparation, I honestly 24 don't remember. 129 1 Q Was there a claim made of 2 some adverse event associated with that vitamin 3 product? 4 A I think so, but I don't 5 really remember. 6 Q Do you recall when that 7 was? 8 A My best recollection is 9 something like '86; '85, '86, '87. 10 Q So of all the depositions 11 you've given for any purpose, how many depositions 12 have you given? 13 A Seventy-five to ninety. 14 Q And for in-court 15 testimony for in purpose -- for any purpose, how 16 many in-court appearances have you made? 17 A About a dozen. 18 Q Have you been asked to 19 testify at the trial of any of the cases made the 20 subject of these lawsuits? 21 A Not to my knowledge. 22 Q Do you intend to? 23 A If asked. 24 Q You will attend any of 130 1 these Prozac trials and testify? 2 A Anything that Lilly asks 3 me to do, yes, sir. 4 Q But at this point, you've 5 not been asked to do so? 6 A No, sir. 7 Q Earlier you had said that 8 you were asked to join some department of the 9 United States Food and Drug Administration? 10 A Yes, sir. 11 Q Tell me about that; I 12 wasn't clear. 13 A I'm sorry. 14 Q No, I wasn't clear, you 15 were probably clear, I just wasn't clear; don't 16 apologize. 17 A Before I made the 18 decision to join Lilly, I had been offered the job 19 to replace Doctor Dick Crout, whose title I 20 believe was Director of the Bureau of Drugs. At 21 that time there was a Bureau of Drugs and a Bureau 22 of Biologics, the titles have changed, and I was 23 asked to specifically replace Doctor Crout. 24 Q Is the Bureau of Drugs a 131 1 department of the United States Food and Drug 2 Administration? 3 A Yes, sir. 4 Q Is the Department of 5 Neuropharmacology at the United States Food and 6 Drug Administration part of the Bureau of Drugs at 7 the FDA? 8 A I think its official 9 title is division rather than department, but yes, 10 it is a part of what would now be called the 11 Center for Drug Evaluation and Research, but I 12 believe at that time it was called the Bureau of 13 Drugs. 14 Q It's now known as the 15 Center -- 16 A CDER, the Center for Drug 17 Evaluation and Research. 18 Q And you had been offered 19 the job as director of the Bureau of Drugs, which 20 is now the Center of Drug Evaluation and Research? 21 A Yes, sir. 22 Q Of which the Department 23 of Neuropharmacology is a division? 24 A I think its called a 132 1 division rather than a department, but that is a 2 part of it, yes, sir. 3 Q Who was the director of 4 the Bureau of Drugs that took the job that you 5 were offered? 6 A They asked Doctor Hank 7 Myers, who was director of the Bureau of 8 Biologics, to assume responsibility for both 9 biologics and drugs. 10 Q All right, then who 11 followed him as the director of the Center of Drug 12 Evaluation and Research? 13 A Doctor Carl Peck. 14 Q And who followed him? 15 A Now another person from 16 biologics, Doctor Janet Woodcock has taken that 17 job. 18 Q Some of the names that 19 we've heard mentioned at the FDA in connection 20 with Prozac are Leber, Doctor Paul Leber? 21 A Yes, sir. 22 Q Doctor Tom Laughren? 23 A Laughren, yes, sir. 24 Q That's how it's 133 1 pronounced, Laughren? 2 A Yes, sir. 3 Q And Doctor Robert Temple? 4 A Yes, sir. 5 Q Is it Robert Temple? 6 A Yes, sir. 7 Q Were those individuals 8 present or were they employees of the FDA when you 9 were offered the job of Director of the Bureau of 10 Drugs? 11 A Doctor Temple was, and I 12 can't speak to whether Doctor Leber or Laughren 13 were employees at that time or not. 14 Q Doctor Temple is the 15 senior of the three individuals we mentioned, is 16 he not? 17 A Yes, sir. 18 Q And his specific title 19 is -- 20 A I can only be close now, 21 he's Director of the Office of Drug Evaluation and 22 Research, I think it's number one, but it might be 23 number two. 24 Q So if you had taken the 134 1 job as the Director of the Bureau of Drugs, which 2 is now the Center for Drug Evaluation and 3 Research, you would have been senior to Doctor 4 Robert Temple, is that right? 5 A At that time, yes, sir. 6 Q Did you apply for that 7 job? 8 A No, sir. 9 Q How were you recruited 10 for that job? 11 A I was asked by the search 12 committee to consider taking that position, and I 13 applied in the sense that they sent me a large 14 amount of paper work which I dutifully completed. 15 Q Who was -- had the FDA 16 formed a search committee? 17 A Yes, sir. 18 Q Who was on that search 19 committee, do you recall? 20 A No, sir, I'm sorry, it 21 had many people, being none of whom I knew very 22 well at all. 23 Q Was Doctor Temple on that 24 search committee? 135 1 A No, sir. 2 Q Was Doctor Carl Peck on 3 that search committee? 4 A I don't think so. 5 Q Who was the chairman of 6 the Food and Drug Administration, or 7 commissioner -- is it chairman or commissioner? 8 A Commissioner. 9 Q Commissioner of the FDA 10 at the time you were offered the job? 11 A Doctor Arthur Hayes. 12 Q Did you know him? 13 A Yes, sir. 14 Q How did you know him? 15 A He was a clinical 16 pharmacologist, I was a clinical pharmacologist; 17 we had often attended the same meetings. 18 Q Then who followed Doctor 19 Hayes as commissioner of the Food and Drug 20 Administration? 21 A I think Doctor Goyen was 22 next. Do you want me to keep going? 23 Q Uh-huh. 24 A I'm blocking on the guy 136 1 who was dean at Rochester who went next, who was 2 then followed by Doctor Kessler. I'm sorry, I 3 have forgotten the name, I'm blocking the name of 4 the one in the middle. 5 Q Do you know Doctor 6 Kessler? 7 A Yes, sir. 8 Q How do you know Doctor 9 Kessler? 10 A Well, we both trained at 11 Johns Hopkins, and we've had some meetings since 12 he assumed his position at the FDA. 13 Q Did you train together at 14 Johns Hopkins? 15 A Contemporaneously, we 16 were both there. 17 Q Did you know him while he 18 was at Johns Hopkins? 19 A Well, to speak to him, 20 yes. 21 Q Classmates? 22 A No. 23 Q Who would have been 24 senior of the other? 137 1 A I think I'm older than 2 Doctor Kessler by a fair amount. 3 Q Beg your pardon? 4 A I think I'm older by a 5 fair amount than he is. 6 Q Do you see Doctor Kessler 7 socially? 8 A I have once been to his 9 home, but it was a business meeting, not a social 10 meeting, and I don't recall ever meeting him 11 social. 12 Q Has he been to your home? 13 A No, sir. 14 Q But you would know Doctor 15 Kessler if you met him? 16 A Oh, yes, sir. 17 Q And he would know you? 18 A Yes, sir. 19 Q He would know who you 20 are? 21 A Yes, sir. 22 Q What your background is? 23 A Yes, sir. 24 Q What your current 138 1 employment is? 2 A Yes, sir. 3 Q And he's followed your 4 career? 5 A I think all of your 6 previous statements are correct, I don't know 7 whether following my career is correct or not. 8 Q Well, he's aware of 9 basically what training you've had, how long 10 you've been with Lilly, what the various positions 11 you've had at Lilly? 12 A I think that's correct. 13 Q You've been familiar with 14 his career -- 15 A Yes, sir. 16 Q -- also. What was his 17 job before he was commissioner of the Food and 18 Drug Administration? 19 A He was director of the 20 major hospital in the Albert Einstein University 21 system. 22 Q And you and he 23 communicated when he was at the Albert Einstein 24 system? 139 1 A I don't believe so. 2 Q Have you met with Doctor 3 Kessler specifically on the subject of Prozac? 4 A I don't believe so. 5 Q Are you sure of that? 6 You say I don't believe so. 7 A Well, I have a lot of 8 far-ranging conversations whenever I meet with him 9 on a variety of topics, but there were none that 10 were specific to Prozac that I can recall. 11 Q Have you ever discussed 12 with Doctor Kessler the issue of Prozac and 13 suicidality? 14 A Yes, sir, I do recall 15 having that in part of a meeting, but that wasn't 16 the purpose of the meeting. 17 Q When was that meeting? 18 A It was either in -- it 19 was probably in 1991, but it could have been 1992. 20 Q Where was that meeting? 21 A When that subject came 22 up, that meeting was at his home. 23 Q How did the subject come 24 up? 140 1 A We were talking about a 2 whole number of scientific things at Lilly in 3 which that was one of many that we talked about at 4 that time. 5 Q What was said about it, 6 Doctor Thompson; what did you say about it and 7 what did he say about it? 8 A I don't recall what he 9 said about it, but I recall that what I said about 10 it was to give him in essence a status report on 11 what the scientific information was addressing 12 that issue at that time. 13 Q I assume then he asked 14 for a status report, informally at his home? 15 A I don't honestly remember 16 whether he asked for it or I just brought it up, 17 because we, as I recall, went through a whole 18 series of scientific things that were happening at 19 Lilly. 20 Q Did you and he have an 21 agenda that you were going to discuss, Doctor 22 Thompson? 23 A Not any -- well, not a 24 formal agenda, no. 141 1 Q Who else was present at 2 this meeting? 3 A No one. 4 Q Just you and he? 5 A Yes, sir. 6 Q Where specifically did -- 7 you say it was in his home? 8 A Yes, sir. 9 Q Where specifically in his 10 home was it? 11 A It was sitting in sort of 12 the back yard because he was in the process of 13 moving in, and I'm not sure how much furniture was 14 in his house because again I came to the front 15 door and we went to the back yard where there were 16 some chairs to sit in. 17 Q Part of the house was 18 vacant, you had to go in the back yard to have a 19 place to sit down, or that was a convenient place 20 to go since there was moving going on? 21 A That's where he led me to 22 and I followed. 23 Q How long did the meeting 24 last? 142 1 A An hour maybe, at most. 2 Q Where was his home at 3 that time? 4 A Somewhere in the -- 5 either the Bethesda or the Rockville area. 6 Q He was commissioner of 7 the Food and Drug Administration at the time of 8 this meeting? 9 A Yes, sir. 10 Q And you were -- were you 11 the chief scientific officer of the corporation at 12 that time? 13 A No, sir, I think that was 14 probably when I was an executive vice president of 15 LRL. 16 Q And why did you have the 17 meeting at his house? 18 A Because he was in the 19 process of moving and was in, as I recall, fairly 20 informal clothes and he was unpacking boxes or 21 moving things around, and we wanted to meet that 22 day and he suggested coming to his house rather 23 than his office. 24 Q Did you have dinner or 143 1 supper with him? 2 A Oh, no, sir. 3 Q Beg pardon? 4 A No, sir. 5 Q Did he have anybody there 6 taking notes? 7 A No, sir. 8 Q Did you have anybody with 9 you taking notes? 10 A No, sir. 11 Q He was alone and you were 12 alone? 13 A Yes, sir. 14 Q It was a one-on-one 15 conversation? 16 A Yes, sir. 17 Q In his back yard? 18 A Yes, sir. 19 Q And there were a number 20 of issues that came up? 21 A Yes, sir. 22 Q Did all of those issues 23 involve Lilly products? 24 A Most of them. I mean, we 144 1 were mostly talking about Lilly science and so 2 forth; there were other issues as well as. 3 Q Had you requested the 4 meeting or had he requested the meeting? 5 A I think he had requested 6 the meeting. 7 Q Did he request that 8 meeting in a letter form? 9 A I don't think so because 10 we haven't exchanged very many letters. I mean, 11 that isn't a common way that we communicate with 12 each other. 13 Q What is the common way 14 that you communicate with Doctor Kessler? 15 A By telephone or by a 16 personal meeting. 17 Q You had the ability to 18 pick up the phone and call Doctor Kessler on the 19 telephone? 20 A Well, I have that 21 ability; sometimes he answers and sometimes he 22 doesn't. 23 Q You have a number that 24 will get to Doctor Kessler? 145 1 A Well, I have the same 2 number you have for him, and sometimes he talks to 3 me and sometimes he doesn't. 4 Q Well, he's never talked 5 to me, and I've not been in his home either. 6 A Well, the reason we were 7 at his home was very unusual, and as we've already 8 established, I think it was the only home of 9 anybody in government I've ever been to, but it 10 was specifically because he wanted to meet -- we 11 had set the date and he asked if rather than 12 meeting in his office we could meet there because 13 he was in the middle of unpacking a bunch of 14 boxes. It didn't seem unusual to me, it was in 15 the middle of the day and -- 16 Q Well -- but there was a 17 purpose to the meeting? 18 A Yes, sir. 19 Q I assume there was some 20 informal discussion concerning maybe areas of 21 mutual interest or people of mutual interest, 22 correct? 23 A Yes, sir. 24 Q But then there was some 146 1 specific issues that you wanted to discuss with 2 him and he wanted to discuss with you, is that 3 correct? 4 A Yes, sir. 5 Q Don't let me put words in 6 your mouth, but one of those issues was Prozac and 7 suicidality? 8 A Neither one of us had 9 planned -- neither one of us in discussing the 10 meeting had in fact established that as anything 11 that we would talk about. However, at the 12 meeting, as we went through a number of scientific 13 things that were going on, both at Lilly and at 14 the FDA, that was one of the issues which came up, 15 which therefore I responded to your question by 16 saying yes, I could recall that conversation which 17 did touch on Prozac and did touch on those issues 18 with Prozac at that time. 19 Q I've seen a number of 20 documents that you've authored, and I've seen a 21 number of documents of other individuals at Lilly, 22 and you don't appear to me, from reading your 23 documents, Doctor Thompson, to be an individual 24 who would go to Doctor Kessler's home or have a 147 1 meeting with Doctor Kessler without having some 2 type of agenda of issues that you wanted to cover 3 with Doctor Kessler. He's a busy man and you're a 4 busy man. 5 A There was a primary issue 6 that was the occasion of the meeting; however, as 7 I've indicated to you, we then got off into a 8 variety of other scientific issues. My agenda 9 with him has usually been trying to change the way 10 in which clinical trials are pursued; that's been 11 a very consistent theme with my meetings with high 12 level people at the FDA. 13 Q Is that -- was that what 14 the subject -- you said the primary reason for my 15 meeting with him. What was the primary reason? 16 A His primary reason for 17 meeting with me is he was recruiting me. 18 Q Doctor -- I mean Doctor 19 Kessler was recruiting you? 20 A Yes, sir. 21 Q To do what? 22 A To be a deputy 23 commissioner of the FDA responsible for 24 operations. 148 1 Q And when were you first 2 approached in connection with this? 3 A Within a few months of 4 his becoming commissioner, and I can't tell you 5 the exact date, but you can look up whenever that 6 was. 7 Q I don't remember when he 8 became commissioner, it seems like forever. Can 9 you tell help me? 10 MS. ZETTLER: Right 11 before Bush left office. 12 A I think it was perhaps 13 even a year before Bush left office that he was 14 commissioner, so within a month or two of his 15 taking that job was when he approached me. 16 Q And he first approached 17 you within a month or two from the time he became 18 the commissioner of the Food and Drug 19 Administration, correct? 20 A To the best of my 21 recollection. 22 Q Now, is this meeting that 23 you had in his home also within a month or two 24 from the time that he approached you? 149 1 A No, I think we had our 2 first meeting in his downtown office; we had 3 another conversation on this subject in his 4 Rockville office, the Parklawn Building office; 5 and I think this was the third and last meeting on 6 the subject, but it was within a few months of the 7 first one. 8 Q How did he initially 9 contact you, did he call on the phone? 10 A Yes, sir. 11 Q He had been appointed 12 commissioner of the Food and Drug Administration? 13 A Yes, sir. 14 Q Had he been confirmed? 15 A I don't remember. 16 Q But he wanted you to be 17 the deputy commissioner in charge of operations? 18 A Yes, sir. 19 Q What would that have 20 entailed? 21 A I think almost all of the 22 employees of the FDA report to that office with a 23 few exceptions; for example, I think a lot of the 24 systems people report to another deputy 150 1 commissioner, and there's another one responsible 2 for legislative affairs and another responsible 3 for public relations, and there was another who 4 was like a science advisor, but this was the 5 office to which most of the seven thousand or so 6 people would report. 7 Q You would be, I guess 8 then, his number one man? 9 A No, I think he has either 10 five or six deputy commissioners. 11 Q But this would be the 12 primary deputy commissioner, it sounded like to 13 me, commissioner of operations. 14 A For the purpose of 15 operations. 16 Q Well, did you tell 17 anybody at Lilly that you had been approached -- 18 A Yes, sir. 19 Q -- for this job? 20 A Yes, sir. 21 Q Did you tell -- who did 22 you tell? 23 A Doctor Perelman, 24 Mr. Mitch Daniels, and Doctor Herr for sure; I 151 1 don't remember who else was involved. 2 Q Perelman and Herr -- 3 well, Perelman was -- 4 A My boss. 5 Q -- your immediate boss? 6 A Yes, sir. 7 Q Herr was another vice 8 president, is that right? 9 A He was Doctor Perelman's 10 immediate boss. 11 Q That's right, that's 12 right. And -- but Mitch Daniels was not superior 13 to you at all, was he? 14 A No. 15 Q Why did you talk to Mitch 16 Daniels, because of his insight into government 17 workings, operations? 18 A Exactly. 19 Q What did Doctor Herr and 20 Doctor Perelman say about you taking this job, 21 Doctor Thompson? 22 A They didn't want me to 23 leave Lilly, but they were -- 24 Q That's because they were 152 1 satisfied with the job you were doing? 2 A I hope so. 3 Q What did they tell you in 4 connection with whether they thought it would be 5 good for you? 6 A I don't recall that we 7 had a long conversation about that; I told them 8 that because of my respect for Doctor Kessler, 9 that I thought it would at least be polite to go 10 and talk with him about it rather than turning him 11 down over the phone, but I wanted them to 12 understand that I was being totally open and 13 candid with them as well. 14 Q I would assume you were 15 flattered by the offer of the job? 16 A It was not a position 17 that I had sought, it was a position that I didn't 18 take, but it's always nice to be thought of as 19 capable of doing something. 20 Q Well, it would have been 21 an extremely big job with a lot of responsibility, 22 as you say, seven thousand employees? 23 A I don't think I've ever 24 measured my jobs that way, but it would have been 153 1 an interesting challenge. 2 Q So you went and talked to 3 Doctor Kessler downtown? 4 A Yes, sir. 5 Q And how long did that 6 meeting last? 7 A About a -- it took up 8 most of the day. You had asked me earlier about 9 lunch; as a matter of fact, we did go to lunch 10 with a number of people on his staff during 11 that -- it was virtually a day long meeting. 12 Q He was already 13 commissioner of the Food and Drug Administration 14 at that time? 15 A Yes, sir. 16 Q And give me a date as to 17 when that would have been? 18 A That date was the same 19 time that he took a public action that had to do 20 with orange juice as I recall, and you would have 21 to look that one up because again I can't remember 22 explicitly. I just remember that that news story 23 on orange juice and something to do with orange 24 juice labeling was breaking at that time. 154 1 Q Okay, Bush left in 1992, 2 right? 3 A I think he actually left 4 in -- don't they get elected in an even numbered 5 year and they leave in January of the following 6 year. 7 Q So this would have 8 probably been in '93 that you had the first 9 meeting? 10 A No, I think it was when 11 Bush was very -- 12 Q '91? 13 A I think it was very early 14 on in Doctor Kessler's appointment, but I don't 15 honestly remember. We could look up what the date 16 of the orange juice action and -- because part of 17 the discussion obviously was that this job was 18 responsible not just for drugs and biologics, for 19 all the components at FDA. 20 Q Did you discuss Prozac 21 during that meeting? 22 A No. 23 Q The Teicher article had 24 been published by the time of that meeting, had it 155 1 not? 2 A You said so. 3 Q Well, the Teicher article 4 was published in February 1990. 5 A That would have antedated 6 this meeting. 7 Q So the controversy was in 8 existence, can we use that term? 9 A Yes, sir. 10 Q But you and he didn't 11 discuss that at that time? 12 A I'm pretty sure that I 13 don't think that came up during that meeting. 14 Q But not positive? 15 A No, sir, it was a long, 16 long day. 17 Q The FDA advisory 18 committee on this issue was held in September of 19 1991, correct? 20 A I can't remember 21 explicitly, but I'm sure you're right. 22 Q That first meeting was 23 before -- was that before that advisory committee 24 meeting? 156 1 A I don't remember it 2 because it wasn't connected in any sort of way, so 3 I can't remember if it was before or after. 4 Q So that downtown meeting 5 lasted all day, correct? 6 A Yes, and it wasn't just 7 at one office. I mean, I met with a number of the 8 other people who were coming on board to be his 9 deputy commissioners and associate commissioners. 10 Again I remember that a group of us, including 11 him, went out to somewhere for lunch. 12 Q Could you have -- to do 13 this job, could you have taken a leave of absence 14 from Lilly and returned to Lilly had you decided 15 to do that? 16 A Well, I never explored 17 that, but I'm sure the answer is no. 18 Q You would have had to 19 actually resign your position at Lilly? 20 A Again, it was never 21 explored, but I'm sure the answer is that would be 22 correct. 23 Q So you had a second 24 meeting in Rockville with him -- 157 1 A Yes, sir. 2 Q -- concerning this issue, 3 and how long after the first meeting was it? 4 A Within a few weeks; I 5 can't date it explicitly. 6 Q I'm assuming that you 7 didn't turn him down at the first meeting and you 8 were still considering this position on -- by the 9 time of the second meeting? 10 A I was never greatly -- I 11 was not eager to accept this position, but I had 12 not turned him down until the last meeting at his 13 home. 14 Q But he was still 15 pressuring you then, at least by the time of the 16 second meeting to join him? 17 A Yes, sir. 18 Q What was the subject of 19 the second meeting? 20 A It was the same thing, 21 going over what his vision of what this role would 22 be because it was a new role, and what he wanted 23 to accomplish in it, why he thought that I could 24 do it, and why he thought it would be a meaningful 158 1 career experience for me. 2 Q Did you report to Doctor 3 Perelman or Doctor Herr the results of your first 4 meeting with Doctor Kessler? 5 A Yes, sir, I'm sure I told 6 Doctor Perelman about all the meetings. 7 Q And what was his 8 reaction? 9 A I don't remember any 10 particular reaction other than that they didn't 11 want me to leave Lilly. 12 Q Well, did you ask his 13 advice on what you should do? Doctor Perelman, in 14 all kindness to Doctor Perelman, is older than 15 you, was senior to you, and I would have thought 16 you might have sought his advice. 17 A I may have. I really 18 can't remember the details. 19 Q Do you remember what he 20 suggested that you do? 21 A Well, I remember his 22 suggesting that I continue to work for Lilly. 23 Q Did he say look, Leigh, 24 if you want to go over there, you know, we're not 159 1 going to hold you back? 2 A I don't remember the 3 exact words; I'm sure that had I in fact wanted to 4 accept the job that Lilly would have been willing 5 to let me go. 6 Q Obviously, you know, you 7 weren't Lilly's servant, I mean, but you felt like 8 that upper management would have still held you in 9 high regard had you taken the job with the Food 10 and Drug Administration? 11 A I would have hoped so. 12 Q So did you report to 13 Doctor Perelman and Doctor Herr the results of the 14 second meeting? 15 A Yes, sir. 16 Q And what did happen on 17 the second meeting? 18 A Again, Doctor Kessler 19 explained in more detail exactly what his plans 20 were and he had more information about the exact 21 composition of his team, and he was just trying to 22 talk me into taking the job and I was asking 23 questions. 24 Q It sounds like you were 160 1 still considering it. 2 A I was genuine in the 3 sense that I had not made up my mind to say no, 4 but continued to meet with him, but there was a 5 very low probability of my taking the job. 6 Q Did you discuss Prozac 7 and suicide and violent aggressive behavior on 8 that second meeting? 9 A I'm pretty sure the 10 answer is no. 11 Q Did you take notes or did 12 he take notes during that second meeting? 13 A I'm sure I didn't take 14 notes, and I don't recall whether he did or not. 15 Q And then the third 16 meeting was at his home? 17 A Yes, sir. 18 Q How much time elapsed 19 between the second meeting and the third meeting? 20 A A couple of weeks. 21 Q And you did tell him no? 22 A Yes, sir. 23 Q What reason did you give 24 him for declining the job? 161 1 A I told him that at that 2 stage in my career, I didn't want to take a job 3 that would not last out until the end of my career 4 and retirement, and his focus in recruiting me was 5 largely -- in fact he had made a big point that 6 this could be something I would do for two years 7 or four years or five years and then go on to 8 something else, and I told him that I found that 9 particularly unattractive at my age and my stage 10 of the career, that in fact if anything I would 11 not want to move once, much less move twice more 12 before I finished my career, and I also shared 13 with him my concerns about the ability -- his 14 primary interest in recruiting me was his respect 15 for how Lilly had modified the clinical trial 16 process and made it more efficient and more 17 elegant, and he thought that I could in fact make 18 the same kinds of influences on the FDA reviewers, 19 and I told him that my primary concern was that 20 although I felt that I could impact in the first 21 few layers of the administrative hierarchy at FDA, 22 that it was a very major process to actually 23 change and improve the scientific acumen of a 24 large number of their staff, and that I wasn't 162 1 sure that in a period of a few years I could 2 effect enough meaningful change that I would feel 3 good about my own accomplishments. 4 Q How did he take that? 5 A I think he understood, 6 and -- I mean, we had a very open and candid 7 discussion about what I could do and what my 8 strengths were and what my weaknesses were and 9 what I could expect, and I think he understood 10 exactly where I was coming from. 11 Q So did the subject of 12 Prozac and suicide come up in that third meeting 13 before or after you had turned him down -- 14 A After. 15 Q -- in connection with his 16 job offer? 17 A After. 18 Q And what did you tell him 19 about the status of Prozac and suicidality and 20 violent aggressive behavior? 21 A I just told him that we 22 had continued to accumulate more and more 23 scientific information and that we had gone to a 24 number of experts around the world, the best that 163 1 we could seek out in terms of experts in this 2 area, and that we thought there was mounting 3 evidence to insure that in fact there wasn't a 4 problem in terms of a causal relationship between 5 Prozac and those events. 6 Q Did you tell him what 7 consultants you had been visiting with about this? 8 A I don't think so. 9 Q Did you consult -- did 10 you advise him concerning any particular clinical 11 trials that you were doing on this issue? 12 A I don't think -- I think 13 this was a very short conversation about Prozac, 14 and I don't think there were a lot of details gone 15 into; I don't recall any specific details. 16 Q Well, since this issue 17 has arisen, Lilly hasn't done any clinical trials 18 specifically examining the issue of whether or not 19 Prozac is related to suicide, have they? 20 A Yes, we have. 21 Q Which trials have they 22 done -- 23 A We've done -- 24 Q -- examining the issue of 164 1 whether or not Prozac is related to suicide? 2 A We've done a large number 3 of clinical trials that are prospective, 4 randomized, double blind, and well controlled 5 trials in patients both with depression and other 6 illnesses in which we've collected explicit data 7 both on suicidal thinking, suicidal acts, suicide 8 itself, and all other adverse events. 9 Q I want you to tell me 10 about those trials. 11 A We've done a large number 12 of trials over a number of different diseases, 13 including both depression, obsessive compulsive 14 disease, weight loss, smoking cessation, bulimia, 15 that were prospective, double blind, randomized, 16 well controlled, in which we were explicitly 17 collecting data that addressed suicidal thinking 18 acts and suicide, as well as explicitly addressing 19 all other adverse events to the drug. 20 Q Tell me what depression 21 protocol has been done that addresses the issue of 22 suicidality and employs any scale other than the 23 Hamilton depression scale to measure suicidality 24 in patients subject to that trial. 165 1 A But the Hamilton 2 depression scale is by far the best validated and 3 most accurate. 4 Q No, I didn't ask you 5 that, and I'm going to ask you to be responsive to 6 the question I've asked. I'm going to have the 7 court reporter read it back, Doctor Thompson, and 8 I want you to answer the question that I've asked, 9 please, sir. 10 REPORTER: (READING) Tell 11 me what depression protocol has been done that 12 addresses the issue of suicidality and employs any 13 scale other than the Hamilton depression scale to 14 measure suicidality in patients subject to that 15 trial. 16 A I'm not aware of any 17 specific scale that specifically addresses 18 suicidality other than the Hamilton depression 19 scale included in a well-controlled, adequate, 20 prospective double blind study. 21 Q So is the answer to my 22 question none? 23 A The answer to your 24 explicit question is none, but a full answer to 166 1 your question needs to be qualified because of the 2 informational content in our controlled trials. 3 Q Well, there are specific 4 scales, are there not, Doctor Thompson, that 5 address suicidality, are there not? 6 A There are scales that we 7 were attempting to validate to make use of in a 8 prospective study, yes. 9 Q Were any of those done in 10 a prospective study? 11 A I believe the Marie 12 Asberg scale, which was included in some of our 13 trials, especially international, have questions 14 which address that issue. 15 Q Okay, which trials? 16 A I can't give you the 17 protocol numbers without referring to the 18 records. There have been hundreds of trials done 19 with Prozac. 20 Q Yes, and my question is: 21 Specifically what was done in those trials to 22 assess suicidality in the participants in those 23 trials? 24 A Thank you, because that 167 1 allows me to point out the fact that on virtually 2 every visit of every patient to the investigator 3 in those trials, a complete inventory of adverse 4 events was in fact elicited in a very well- 5 controlled manner, in addition to which -- 6 Q How? I didn't mean to 7 interrupt you, and I'll try not to do that, but 8 how was that addressed in a specific manner? 9 A On most of our clinical 10 report forms sets, for every visit there is an 11 explicit page, or pages, for the investigator to 12 recall all adverse events, and in all of our 13 training of investigators, in our letters of 14 agreement with investigators, and in our protocols 15 and in our instructions for doing the clinical 16 trial we go to great lengths to explain to the 17 investigators how to collect all adverse events 18 and how, in fact, to give us complete information 19 about them. 20 Q Well -- 21 A Can I -- don't forget, 22 we've still got part of it that you interrupted. 23 Q I understand that, and 24 don't let me -- I'll let you get back to that, but 168 1 are you saying that the investigator is measuring 2 suicidality in these clinical trials by virtue of 3 the fact that he is recording any adverse events 4 that might occur during the course of the trial? 5 A That's one of the ways in 6 which that would be recorded, yes. 7 Q All right. 8 MR. FREEMAN: Go ahead 9 and complete your answer. 10 A Well, in addition, the 11 Hamilton depression scale was used, I believe, in 12 all of the controlled depression trials in the 13 United States; either the Hamilton depression 14 scale or another very well validated scale like 15 Marie Asberg's scale was used in the international 16 trials, in addition to which other scales which 17 would address symptoms that could, in fact, 18 reflect suicidality, like the symptom checklist, 19 were included in many of those protocols, but the 20 combination of an explicit question on the 21 Hamilton depression scale, by far the most 22 validated and widely accepted scale that 23 specifically addresses suicidal thinking, 24 gestures, acts and suicide, being included in 169 1 virtually all of the trials, at least in the 2 United States of depression, and our extreme 3 efforts to record all adverse events clearly means 4 that virtually on every visit of every patient in 5 those trials there was an explicit elicitation of 6 anything that could reflect on suicidal thinking, 7 acts, gestures or suicide. 8 Q Are you saying that's 9 true for even the clinical trials that were run 10 prior to submission of the NDA? 11 A Most of them in 12 depression included the Hamilton depression 13 scale. I can't guarantee that all of them did, 14 but certainly adverse events were elicited. The 15 manner in which we elicited adverse events, 16 however, has evolved over time, so that -- 17 Q Are you saying that's 18 changed? 19 A Yes, sir. 20 Q How has it changed? 21 A Somewhere around 19 -- 22 late 1982, early 1983, we put in place a variety 23 of changes that specifically address both the 24 elicitation validation and recording of adverse 170 1 event data and other safety data. 2 Q I don't understand that, 3 you'll have to expand on that a little bit more. 4 A I'm sorry, we -- the way 5 in which this was done, the standard operating 6 procedures changed and the timing was, I think, 7 early -- either late '82 or early '83 in which we 8 changed the operating procedures to provide much 9 more detailed instructions to the investigators 10 and more detailed ways of eliciting all adverse 11 events, validating those reports, recording them 12 in our computers and analyzing them. 13 Q Are you talking about the 14 change where you said there's not going to be any 15 more marginal notes and that all we're going to do 16 is record data that can be recorded by computer? 17 A That was one of perhaps 18 dozens of changes in the standard operating 19 procedure, yes. 20 Q And it's your position 21 that that is more sophisticated in picking up 22 expressions of sides effects and adverse events? 23 A Well, the change from 24 having marginal notes that weren't validated to 171 1 having explicit instructions about how to record 2 all observations relating to adverse events, 3 providing a large area in which to record those, 4 and the validation procedures that we went through 5 with those, yes, that greatly increased the -- 6 both the capture, integrity and the validation; 7 but remember, that was only one of a whole number 8 of changes that were made at about the same time. 9 Q Is it your position that 10 the clinical trials that were done were intended 11 to assess the issue of suicidality in depressed 12 patients? 13 A Suicidality is a -- both 14 is a part of the disease depression, and any of 15 its treatment was in fact one of -- one of many 16 objects of those clinical trials, yes, indeed. 17 Q So is it your testimony 18 that Lilly was concerned about whether or not 19 Prozac could cause an increase in suicidal 20 ideation, so they developed protocols from the 21 outset to examine this issue? 22 MR. FREEMAN: You've 23 asked two questions in one, you said cause and 24 then you said contribute to or something like 172 1 that. Answer one of them first and let him know 2 which one you're answering. 3 A Well, first of all, Lilly 4 is concerned in our clinical trials in the 5 original NDA, in assessing all of the safety 6 aspects of the drug, as we are with any drug that 7 we put into humans for the first time. So we had 8 no more specific interest in causal -- causing 9 suicidality than we did in causing any of the 10 other kinds of safety events that could occur. 11 However, because we included in there the best 12 validated scale that specifically addressed the 13 issue of suicidal thinking, acts, gestures and 14 suicide, in fact we had a very objective and very 15 highly validated way of assessing that, and went 16 to extreme lengths to make sure the investigators 17 were very well trained in how to apply that scale 18 to minimize inter-investigator and 19 intra-investigator variability in terms of how 20 they completed that scale. 21 Now, in terms of whether 22 we specifically designed a study to address the 23 issue of suicidality separate from all of the 24 other issues of efficacy and safety, the answer is 173 1 no. 2 Q You didn't then, you 3 haven't now either, have you? 4 A We've worked extremely 5 hard on trying to figure out how to address that 6 issue; yes, indeed we've spent an awfully lot of 7 time and money on trying to figure out how to do 8 it. 9 Q How much time? 10 A Of my time or total 11 people at Lilly? 12 Q Whatever the time we're 13 speaking of when you say we spent an awfully lot 14 of time and money. 15 A Well, I can say that I 16 personally have spent hundreds of hours on this 17 specific issue, talking to experts, reading the 18 literature and trying to decide how we could 19 possibly do these kinds of studies. I can only 20 speak for myself, but I know that many other 21 people spent far more time than I did at Lilly 22 working on this. 23 Q Has anybody figured that 24 out yet? 174 1 A Not to my knowledge. 2 Q How much money has been 3 spent? 4 A I don't know what the 5 total amount of spending would be, but we 6 certainly have done two things. First of all, 7 this issue is addressed, as I indicated before, by 8 virtually every controlled trial that we've done 9 with this drug, and that -- 10 Q I'm not talking about 11 that. 12 MS. ZETTLER: Motion to 13 strike as nonresponsive. 14 Q I'm talking about you 15 said we spent a lot of time and money trying to 16 figure out what to do to examine this since the 17 issue has come up, and I want to know -- my 18 question was how much money have you spent? 19 A Mr. Smith, I'm trying to 20 tell the whole truth, and you need to understand 21 that the information that we have obtained in 22 trials of other products like tomoxetine, in 23 trials of other molecules in depression, and all 24 of the trials that we have done in depression 175 1 since this first -- question first evolved, first 2 of all it's been very expensive, those analyses 3 have been very extensively taking a lot of time, 4 and all of them bear directly upon this issue. 5 Q Okay, how much expense 6 has there been expended by Eli Lilly and Company 7 on this issue? 8 MR. FREEMAN: If you 9 know, tell him. If you don't, tell him. 10 A I certainly don't know. 11 Q You said it's been very 12 expensive. 13 A Yes, sir. 14 Q I would assume that you 15 had some facts; you're not just pulling that out 16 of the top of your head, are you, Doctor Thompson? 17 A No, sir. 18 Q All right, how expensive 19 has it been? 20 A Millions of dollars. 21 Q How many millions? 22 A I don't know. 23 Q Five? 24 A More than that. 176 1 Q Ten? 2 A Of all the clinical 3 trials that we've done, both with fluoxetine and 4 with other molecules in depression in which we 5 have scientifically valid assessment of suicidal 6 thinking, gestures, acts and suicide, it must be 7 closer to a hundred million dollars than to ten. 8 Q All right, but that's on 9 all the clinical trial work you've done on all 10 your antidepressants, isn't it? 11 A Yes, sir. 12 Q What I want to know is, 13 is since this issue has come up, since the Teicher 14 article, you say we've spent a bunch of time 15 trying to figure out a specific way to look at 16 this, we couldn't figure it out, right? 17 A I said that we could not 18 figure out how to design a protocol with this as 19 its specific intent. However -- 20 Q You say -- 21 A Please let me finish and 22 give a complete answer. However, very important 23 scientific information bearing on this question 24 has been derived from all of those trials that I 177 1 addressed. 2 Q Well, how about a 3 prospective clinical trial assessing the specific 4 issue of Prozac and suicidality, there's not been 5 any, has there? 6 A Sir, I want to be very 7 careful to make sure that I tell the whole truth. 8 Every trial that we've done that has been 9 prospective, controlled, double blind and 10 randomized, that has included either a detailed 11 assessment of side effects or the Hamilton 12 depression scale or an equivalent scale or both, 13 has in fact provided extremely important 14 scientific issues, data bearing directly upon this 15 subject. 16 MS. ZETTLER: Motion to 17 strike as nonresponsive. 18 MR. FREEMAN: Overruled. 19 Let's go to lunch. 20 MR. SMITH: Just a 21 second. 22 Q (BY MR. SMITH) Some of 23 those trials had evidence that there was an 24 increase in suicidality in connection with Prozac 178 1 use, wasn't there? 2 A I can't recall a trial in 3 which there was a statistically significant 4 increase in Prozac rather than a comparator, but 5 there certainly could have been because I'm 6 looking at the totality of the information to draw 7 my conclusions and not one investigator or one 8 trial at a time. 9 Q I thought you said all 10 the information was important. 11 A I did say all the 12 information was important, absolutely. 13 Q How much money has been 14 expended? You said a tremendous amount of money 15 has been expended in a new effort to examine the 16 issue of Prozac and suicidality. 17 A You mean other than what 18 I have addressed previously -- 19 Q Yes. 20 A -- in terms of all of 21 these large number of trials? 22 Q Yes, yes. 23 A We've expended a great 24 deal of time and effort and money in trying to 179 1 design a study the primary purpose of which would 2 be to focus on this issue. 3 Q Okay, how much money? 4 A I don't know, sir. 5 Q Well, you said a 6 tremendous amount; I'm sure you didn't just give 7 me a figure without any factual basis, did you? 8 A I don't have any factual 9 basis to estimate that except for my own time and 10 the time of other people and the number of 11 meetings we've had with consultants and the 12 worldwide discussions we've had on this issue 13 trying to find a way of doing those trials. 14 Q You've sworn under oath 15 that you've expended a tremendous amount of 16 money -- 17 A Yes, sir. 18 Q -- on a new trial -- 19 A Yes, sir. 20 Q -- that would examine 21 this specific issue. 22 A Yes, sir. 23 Q How much money? 24 A I don't know, sir. 180 1 Q Then how can you 2 characterize it as a tremendous amount of money? 3 A Well, a million dollars 4 seems like a tremendous amount of money to me. 5 Q Okay, has it been more 6 than a million dollars? 7 A I think so. 8 Q Has it been more than 9 five million dollars? 10 A I don't know. I can't 11 place it any more accurately than that. 12 Q Has that been in terms of 13 grants that have been issued to somebody? 14 A We've had grants, we've 15 had consultants, we've had a number of meetings, 16 and remember, we've used up a great deal of our 17 own time internally with experts within Lilly. 18 Q Who has received a grant 19 to try to figure out an appropriate protocol to 20 analyze this issue? 21 A The best I can recall, we 22 went to one person who had in fact developed a 23 scale that was specific for suicidality. 24 Q And who was that? 181 1 A I don't remember whether 2 it was Doctor Winokur or not, but one of our 3 consultants in this area, and asked that person to 4 work on validating a portion of or an extension of 5 that scale so that we could in fact use it in a 6 scientifically valid study. 7 Q Did you pay him money? 8 A I can't tell you for 9 sure, I don't remember. 10 Q And what were the results 11 of that? 12 A We were never able to 13 obtain a well accepted, well validated scale that 14 we could use that was any better than the Hamilton 15 depression scale, per se, and the method by which 16 we assessed adverse events, and we were never able 17 to identify a patient population or an 18 investigator population who would logistically be 19 able to complete a study of the size necessary to 20 draw valid conclusions. 21 Q Well, what about Doctor 22 Montgomery's study in England? 23 A I know Doctor Montgomery 24 and I know a lot of studies he's done, but I'm not 182 1 sure of the one that you're referring to 2 specifically. 3 Q His study where he was 4 studying people with schizoaffective disorders and 5 looked at Prozac to see whether or not Prozac 6 reduced suicidality in individuals who had had 7 prior suicidality. 8 A I'm not familiar with the 9 details of that study. 10 Q You don't know anything 11 about that? 12 A I didn't say I didn't 13 know anything about it; I know Doctor Montgomery 14 has done a number of studies with fluoxetine, I 15 don't recall the details of that one. 16 Q You don't know whether he 17 has ever done a study on fluoxetine involving the 18 issue of suicidality? 19 A I know that he has spoken 20 on that subject, but I don't know what data that 21 he has that he's done on that subject. 22 Q Do you know whether he's 23 done a study for Prozac on that issue? 24 A No, sir. 183 1 Q I mean for Lilly using 2 Prozac on that issue? 3 A I told you I don't have a 4 specific recollection of that. 5 MR. SMITH: Have you got 6 that? 7 MS. ZETTLER: Yes. 8 (LUNCH BREAK TAKEN.) 9 (THOMPSON EXHIBIT NO. 4 MARKED FOR 10 IDENTIFICATION.) 11 MR. BOUR: The time is 12 1:55. 13 Q (BY MR. SMITH) As I 14 understand it, as we were discussing before lunch, 15 Doctor Thompson, there has been no study 16 specifically designed to look at the issue of 17 Prozac and suicidality? 18 MR. FREEMAN: Alone. 19 Q Alone. 20 A I think that's correct -- 21 well, I'm not sure that it's fair to say it hasn't 22 been designed, it hasn't been carried out. 23 Q All right. And the 24 reason that it hasn't been carried out is because 184 1 you've had difficulty in designing the proper way 2 or figuring out the proper way to analyze that? 3 A Well, I think there -- 4 excuse me. I think there are three major 5 problems: First of all, in deciding on a 6 validated instrument that would in fact measure it 7 any better than the Hamilton depression scale and 8 the normal elicitation of adverse events. The 9 second thing is in finding investigators who had a 10 rich enough population of patients who in fact 11 manifested suicidal thinking, ideation or acts 12 under treatment with Prozac or similar 13 antidepressants. And thirdly, in finding a 14 sufficient population of patients or in knowing 15 how we could run a study big enough to have enough 16 patients that we could make meaningful conclusions 17 about the relevant incidence rate on Prozac versus 18 a comparator. 19 Q All right, and you're 20 talking about a prospective double blind trial? 21 A Yes, sir; I'm sorry, I 22 thought that's what you were addressing. 23 Q Yes, it was; I just 24 wanted to make sure we were on the same 185 1 wavelength. 2 A Yes, sir. 3 Q Exhibit 4 is a document 4 that has just been submitted to us this last week; 5 however, it appears to be dated January 20th, 6 1993, does it not? 7 A Yes, sir, that's what it 8 appears. 9 Q And it appears that it's 10 a "Prozac Protocol Summary Report Final", correct? 11 A Yes, sir. 12 Q Does that denote that the 13 study has been completed? 14 A Yes, sir. 15 Q It indicates that this 16 was a study titled "Fluoxetine Versus Placebo in 17 Suicidal Patients"? 18 A Yes, sir. 19 Q And there was inpatients 20 and outpatients studied in this trial? 21 A I think that designation 22 actually means that either one could be studied, 23 but I'm not sure it says that they were studied. 24 Q Again, all we have is 186 1 these two page of the document. I can't tell 2 whether there was inpatients and outpatients in 3 the trial or not. Can you, sir, by looking at 4 these two pages? 5 A No, sir, that's why I 6 made the point that normally this part of the 7 global project tracking system talks about what 8 the design is in the sense that both of those 9 patient groups could be included, but without some 10 specific reference that they were included, I 11 wouldn't want to assert that they both were 12 included. 13 Q Can we say at least, 14 Doctor Thompson, that the protocols did not 15 exclude patients who were in the hospital? 16 A I think that's a fair 17 assertion. 18 Q And conversely did not 19 necessarily exclude patients who were not in the 20 hospital? 21 A I think that's correct. 22 In the criteria for evaluation it talks about 23 twenty-four weeks of treatment. It would be 24 pretty unusual to keep a patient in the hospital 187 1 that long, so exactly what the definition of the 2 protocol was, I'm not sure, but I think your 3 assertion is correct. 4 Q That probably it included 5 both inpatient and outpatient? 6 A I think that's likely. 7 Q And it was to be used as 8 a postmarketing clinical experience study, 9 correct? 10 A Yes, sir. 11 Q It says here blinding, 12 single, double, other, on the front page, but then 13 apparently in looking at the second page under 14 methodology, it says randomized, double blind, 15 placebo controlled, parallel group study. 16 A I certainly see that, and 17 furthermore it says matching placebo capsules, but 18 I'm surprised that -- well, on the front page as 19 well it says control drug, placebo. 20 Q Uh-huh. 21 A So it probably was a 22 controlled and, I presume, randomized trial. 23 Q All right. And it was 24 done for clinical efficacy and safety, correct? 188 1 A Yes, sir. 2 Q There they actually 3 enrolled one hundred and seven patients in the 4 study? 5 A Yes, sir. 6 Q Fifty patients dropped 7 out? 8 A Yes, sir. 9 Q Fifty-seven patients 10 completed the study? 11 A That's what it says. 12 Q Have you seen anything 13 about this study at all up to today, Doctor 14 Thompson? 15 A No, sir. 16 Q You know Doctor Stuart 17 Montgomery? 18 A I think I've met him at 19 least once, but I know of him for sure. 20 Q And you know he's been an 21 investigator for Lilly in the past? 22 A Yes, sir. 23 Q And has done -- did you 24 know that he's done other Prozac trials? 189 1 A Yes, sir. 2 Q Do you recall which 3 Prozac trials he's done? 4 A No, sir, I'm not -- not 5 specifically. 6 Q Can you tell me 7 generally; was it for depression or some other 8 indication? 9 A I think he also did 10 either one of the bulimia or obesity trials, but I 11 think he's done several controlled clinical trials 12 for Lilly, as well as been a consultant. 13 Q All right. It says here 14 on the second page, under Study Synopsis, 15 Fluoxetine/Placebo; Suicide Prophylaxis, hyphen, 16 Personality Disorder, correct? 17 A Yes, sir. 18 Q I take it by that, that 19 the individuals who were the subject of this trial 20 would have had a psychiatrist who had diagnosed 21 individuals with a mental illness known as a 22 personality disorder? 23 A That's what I would 24 conclude. 190 1 Q Is it your understanding, 2 based on your training and your experience in the 3 industry and in medicine, that a personality 4 disorder from a psychiatric standpoint could 5 include a number of disorders? 6 A I'm not really an expert 7 in that area. I think there is a reasonable 8 definition of personality disorder among 9 psychiatrists, but I'm not sure it's an explicit, 10 clear, single disorder. 11 Q This study period is for 12 twenty-four weeks? 13 A Yes, sir. 14 Q Is that longer than most 15 of the Prozac clinical trials? 16 A I would say it falls in 17 between because normally you can assess efficacy 18 in depression in a period of six weeks, whereas 19 efficacy in some of the other illnesses require a 20 longer period, but we've also had people under 21 study for six or seven years and we've had a 22 number of protocols that follow people for a year, 23 so this is -- a half a year is sort of in between. 24 Q It says Clinical Phase 191 1 III, what does that mean? 2 A Well, we don't generally 3 use that terminology anymore because we've changed 4 the way clinical trials are done, but in the usual 5 parlance that would mean that it was in a -- 6 usually a preapproval stage for the specific 7 indication, but after from Phase II you're having 8 some evidence of both efficacy and safety. 9 Q Okay, so does -- do you 10 take it from that that it might have been planned 11 that Prozac be used -- this be used to support an 12 indication for Prozac in personality disorders? 13 A I'm unaware that anybody 14 in the corporation had ever intended that, and 15 Phase III and postmarketing clinical experience 16 are generally not the same kind of studies, so -- 17 Q So you just don't have 18 any explanation for why they would have Clinical 19 Phase III here? 20 A No, I don't, not at all. 21 Q It doesn't really make 22 sense, is that what you're saying? 23 A From what I've read, I 24 wouldn't have called it a Phase III study. 192 1 Q It says the objective is 2 to compare the prophylactic effect of fluoxetine 3 and placebo in the prevention of suicidal behavior 4 in nondepressed patients suffering from 5 personality disorders with a history of suicidal 6 behavior, correct? 7 A Yes, sir. 8 Q Do you take it, by virtue 9 of the way this is described, that a history of 10 suicidal behavior would indicate some act or 11 gesture on the part of the participant in the 12 clinical trial? 13 A Well, it does say lower 14 down one of the things they were measuring was 15 suicidal attempt, but I don't honestly know 16 exactly what they meant by suicidal behavior 17 because behavior ordinarily would include more 18 than just thinking, but that's a fine line that 19 without any more information, I wouldn't want to 20 be certain about exactly what they included and 21 didn't include. 22 Q But your impression from 23 reading this would be that they're not examining 24 ideation in this instance, but actually looking at 193 1 acts? 2 A I think that's correct, 3 but again it's an inference that I'm making. 4 Q It appears that the 5 individuals who are going to be studied in this 6 trial were not depressed individuals. 7 A That's what it says. 8 Q But there was going to be 9 administered the MADRS scale, is that right? 10 A Yes, sir. 11 Q That's a depression 12 scale, isn't it? 13 A Yes, sir. 14 Q Why would they be 15 administering a depression scale to nondepressed 16 individuals by definition who had to be in the 17 clinical trials to individuals who were in effect 18 diagnosed as personality disorders? 19 A Well, I think that's a 20 wide range of scores on scales used to measure 21 depression, and between a score that would be low 22 enough that you would say the person was normal 23 and didn't have any evidence of depression, and 24 between what -- the score that would lead you to 194 1 make a positive diagnosis of depression, there's a 2 big gray area in which different psychiatrists 3 would come to different conclusions about whether 4 they were depressed or mildly depressed or 5 whatever. An example of that is bulimia, because 6 I know that at least in some of our trials in 7 bulimia we had excluded people with a score on the 8 Hamilton depression scale high enough to qualify 9 in the range that generally is accepted as a major 10 depression, but on the average those patients 11 scored in between what would be considered normal 12 and considered major depression. So their scores 13 were high enough that one would say they were more 14 depressed than normal, but not depressed enough to 15 have the diagnosis of major depression. 16 So I assume -- and again, 17 this is an assumption because I don't know 18 anything about the study directly, but I assume 19 that that was one of the reasons that they were 20 measuring the MADRS score, in addition to which 21 there are specific questions in the Montgomery 22 Asberg scale that they may have been interested in 23 assessing the individual scores on the subset of 24 the MADRS scales. 195 1 Q Now, the MADRS scale is a 2 depression scale, correct? 3 A Yes, sir, but as in many 4 psychiatric scales, you asked -- it's made up of a 5 series of individual questions and those questions 6 may be related to other illnesses and depression. 7 The reason it's called a depression scale is if 8 you reach a certain level of scoring, then most 9 psychiatrists would say this fulfills the 10 diagnostic criteria for having major depression 11 and an illness. 12 Q But that's the reason you 13 give it is to examine whether or not an individual 14 is depressed; you don't give it to examine whether 15 or not an individual is suicidal, do you? 16 A Only as a part of 17 depression. 18 Q But the Hamilton 19 depression scale is seventeen or twenty-one 20 specific questions, is it not? 21 A Yes, sir. 22 Q And the only question on 23 the Hamilton depression scale relative to suicide 24 is Item 3, isn't it? 196 1 A That's specific for 2 suicidal ideation, gestures, acts -- 3 Q I thought that's what I 4 said; it's the only one that has any -- that has 5 the word suicide in it. 6 A You used the word 7 relevant and I used the word specific, and I think 8 those are two different things. 9 Q Okay. But then the 10 Hamilton depression scale is a scale for 11 depression, is it not? 12 A Yes, but we use the 13 Hamilton depression scale in studies of many other 14 illnesses because those specific questions are 15 highly validated for assessing other aspects of 16 the patient. One reason, the reason Doctor 17 Hamilton invented it was in fact to reach a 18 clinical agreement on how to diagnose depression 19 and measure its severity. 20 Q Nobody -- let's be 21 perfectly clear here, Doctor Thompson. No one has 22 ever validated the Hamilton depression scale for 23 suicidality -- for a measure of suicidality, have 24 they? 197 1 A Well, I'm not sure how to 2 address that because the techniques that one would 3 use to validate a scale are not cut and dried. I 4 would say that the use of the -- do you want me to 5 finish or -- 6 Q Can you answer that yes 7 or no, do you know whether or not anybody has 8 validated the Hamilton depression scale as a 9 measurement of suicidality? 10 A Well, I would say that 11 the studies that Lilly had done using that scale 12 had in fact helped to validate that scale as a 13 measure of suicidality. 14 Q Well, has anybody written 15 a publication at Lilly describing how that the 16 Lilly scientists had all of a sudden validated the 17 Hamilton depression scale for a measurement of 18 suicidality? 19 A Yes, I think Doctor 20 Beasley, et al., had done a very comprehensive 21 analysis of the use of the Hamilton depression 22 scale, not only Question 3, but other subsets of 23 the scale, and that moves towards validation of it 24 as an -- 198 1 Q Are you talking about his 2 famous meta analysis? 3 A Well, I don't know how 4 famous it is, but -- 5 Q It's famous here, Doctor, 6 it's famous. Is that what you're referring to? 7 A His paper in the British 8 Medical Journal? 9 Q Yeah, the one that was 10 rejected by the New England Journal of Medicine. 11 A Oh, yes, you're correct. 12 Q All right. Do you know 13 anybody, other than Doctor Beasley, who has 14 published any article that purports to validate 15 the Hamilton depression scale as a measurement of 16 suicidality, Doctor Thompson? 17 A I don't know of any other 18 specific publications that address that issue. 19 Q All right. You're not a 20 psychiatrist, are you? 21 A No, sir. 22 Q You're not an expert in 23 suicidality, are you? 24 A I would not hold myself 199 1 out to be an expert. 2 Q And you've never sought, 3 yourself, to make any literature search as to 4 whether or not anybody had successfully or even 5 attempted to validate the Hamilton depression 6 scale as a measurement of suicidality, have you? 7 A Yes, I have. 8 Q Anything other than the 9 Beasley article? 10 A I have made such a -- you 11 asked if I had made such a search. 12 Q All right. 13 A And the answer to that is 14 yes, I have. 15 Q What have you found? 16 A I could not find, at the 17 time I did the search, any other article which 18 specifically addressed validation of the Hamilton 19 depression scale. 20 Q When did you make that 21 search? 22 A Three or four years ago. 23 Q Have you tried to keep 24 fairly on top of the literature on that subject to 200 1 see if anybody had done it since you made the 2 search three or four years ago? 3 A I would not want to 4 assert that, no. 5 Q Okay, back to this -- we 6 were distracted from that. The MADRS also only 7 has one question concerning suicidality, doesn't 8 it? 9 A I think that's correct. 10 Q Now, if we look down as 11 to the number of subjects, apparently there was an 12 almost equal number of patients on Prozac and 13 placebo, fifty-four versus fifty-three? 14 A Yes, sir. 15 Q That's no statistical 16 difference, those two numbers, is there? 17 A No, sir. 18 Q The diagnosis and 19 criteria for inclusion indicates that -- 20 A Can we back up for a 21 moment? 22 Q Sure. 23 A I'm using statistical 24 difference in the usual scientific sense of 201 1 statistically significantly different. 2 Q Yes. 3 A You've got to remember 4 that in looking at batting averages, one point at 5 any number of decimal places makes it different if 6 you were picking the person with the highest 7 batting average. So obviously the number 8 fifty-four is different than the number 9 fifty-three, but I just want to make sure that 10 we're talking about the general scientific 11 criteria of statistically significantly different. 12 Q Those two numbers, 13 fifty-four versus fifty-three, normally wouldn't 14 be statistically significantly different? 15 A You're correct. 16 Q And the Hamilton 17 depression scale doesn't look at batting averages, 18 does it? 19 A I don't believe so. 20 Q It doesn't ask the 21 patient's batting average. It indicates that the 22 diagnosis and criteria for inclusion is 23 personality disorders with active suicidal 24 ideation or intent? 202 1 A Yes, sir. 2 Q So that indicates to me 3 that even though it says suicidal behavior, they 4 are using the term ideation there, are they not? 5 A Yes, sir. 6 Q Which normally doesn't 7 connote an act? 8 A I think we may be talking 9 about two different aspects of the study, and 10 again this is my inference from what I've read. 11 One is an entry criteria that would qualify the 12 patient for participation, and the other is an 13 efficacy criteria which would measure whether or 14 not the measured effect was observed. 15 Q All right. 16 A And I would interpret 17 this as meaning that if they had a personality 18 disorder, and at the time of entry to the study 19 had active suicidal ideation or intent, that would 20 qualify to admit them, because that's why it says 21 diagnosis criteria for inclusion. 22 Q Okay. 23 A But very clearly in terms 24 of criteria for evaluation, they talk about 203 1 suicide attempt in less than twenty-four weeks of 2 treatment. 3 Q All right. They were 4 giving here Prozac at sixty milligrams twice 5 weekly, correct? 6 A Yes, sir, that's what it 7 says. 8 Q That's a hundred and 9 twenty milligrams a week? 10 A I think that's what it 11 means on the first page where it gives the dose 12 because you notice there's no indication under 13 frequency of what that means, and there have been 14 a few patients in trials that were treated with 15 doses as high as that a day, but not very many. 16 Q Well, clearly here it 17 indicates that a patient is going to get sixty 18 milligrams twice a week? 19 A Yes, sir. 20 Q A hundred and twenty 21 milligrams per week, but it's not going to be 22 administered on a daily basis, it's going to be 23 administered twice? 24 A That's what it says. 204 1 Q Somebody is going to take 2 a sixty mill -- how would you do that, give them a 3 sixty milligram capsule on Monday, and then on 4 Thursday give them another sixty milligram 5 capsule? 6 A That would certainly be a 7 way of doing it. 8 Q I mean, you wouldn't give 9 them one on Monday and then one on Tuesday, would 10 you? 11 A I wouldn't, but I don't 12 know how the study was designed. 13 Q Well, you wouldn't give 14 it -- you wouldn't think it would be designed that 15 way, would you? 16 A I wouldn't think so. 17 Q Now, the normal 18 recommended therapeutic dosage for Prozac for 19 depression is twenty milligrams once daily, 20 correct? 21 A Yes, sir, but as you 22 pointed out, these patients don't have depression. 23 Q I understand that. If 24 you give twenty milligrams once daily, seven days 205 1 a week, that's a hundred and forty milligrams? 2 A Of course, the upper 3 range of the normal dosage for depression would be 4 eighty milligrams a day, which would be five 5 hundred and sixty milligrams in a week. 6 Q I'm not asking you about 7 the upper range, I'm just asking you if you can 8 multiply seven times twenty and get a hundred and 9 forty. 10 A In base ten arithmetic, 11 that's correct. 12 Q And so a normal depressed 13 individual getting a normal therapeutic dosage of 14 Prozac, as recommended by Lilly, they would be 15 getting less Prozac per week than these patients 16 who were suffering from personality disorder would 17 be getting per week? 18 A I think you had it 19 backwards, sir; I think that the hundred and 20 twenty was the dose per week that this protocol 21 seems to indicate -- 22 Q You think it would be 23 more. 24 A -- and I think the twenty 206 1 times seven would be slightly more. 2 Q Right. Do you see, as a 3 physician familiar with Prozac, a difference in a 4 patient taking one forty and one hundred and 5 twenty milligrams a week? 6 A Well, I can't speak for 7 certainty in this illness because I've not 8 reviewed any data in this illness, but looking at 9 the dose response curves for the other illnesses 10 that I am familiar with, I would say it would be 11 extremely unlikely that you would see a difference 12 between a hundred and twenty and a hundred and 13 forty. 14 Q All right. 15 A But I honestly don't know 16 anything about giving it twice a week because 17 that's not a way in which we've studied the drug 18 very commonly. 19 Q Well, there was some 20 discussion of dose loading at one point, wasn't 21 there? 22 A There's been a whole 23 variety of different kinds of doses suggested and 24 so forth, but I'm not aware that we've done a 207 1 controlled study to look at less than once a day 2 dosing compared with daily dosing. 3 Q Okay. It says that the 4 study would be -- and I don't understand, it says 5 criteria for evaluation, end of study comparing 6 success, twenty-four weeks with no suicide 7 attempts, and failure, suicide attempts less than 8 twenty-four weeks treatment, additional change in 9 MADRS score, correct? 10 A Yes, sir. 11 Q Does that mean that the 12 treatment would be considered a success if a 13 patient didn't attempt suicide within the 14 twenty-four weeks? 15 A I think that's correct. 16 Q But that the treatment 17 would be considered a failure if the patient did 18 attempt suicide within twenty-four weeks? 19 A I agree with that 20 interpretation. 21 Q And you could also look 22 at a change in the MADRS score -- 23 A Yes, sir. 24 Q -- to determine whether 208 1 or not the -- in making an evaluation of the 2 efficacy and safety of the product for that 3 indication? 4 A Yes. I think the primary 5 variable you described before very correctly, and 6 this is an additional variable, and I don't know 7 exactly how they planned to analyze the score, 8 whether they wanted to look at the subsets or 9 whether the total score or what. 10 Q The summary conclusion 11 is -- was that there -- quote, there was no 12 evidence that fluoxetine affected the success 13 rate. Eleven of thirty patients who completed the 14 study made no suicide attempt compared with nine 15 of twenty-seven patients -- what is that P greater 16 than point oh two? 17 A Point two, yes, sir. 18 Q There was also no 19 difference between the treatments in time to 20 suicide attempt. MADRS scores indicated a 21 treatment effect in favor of placebo, paren, P 22 point oh oh six, close paren -- 23 A Yes, sir. 24 Q -- end quote. I find 209 1 that an unusual way to describe a conclusion of a 2 study, do you not; don't you? 3 A No, sir. 4 Q It says: There was no 5 evidence that fluoxetine affected the success 6 rate. Eleven of thirty fluoxetine patients who 7 completed the study made no suicide attempt. Does 8 that mean that nineteen did? 9 A That's the way that I 10 would interpret it. 11 Q It says compared with 12 nine of twenty-seven placebo patients. Does that 13 mean that eighteen did? 14 A That's the way I'd 15 interpret it. 16 Q But that -- and it 17 doesn't give any details, the MADRS score 18 indicated a treatment effect in favor of placebo, 19 correct? 20 A That's what it says. 21 Q That would indicate to me 22 that the patients who were taking the placebo had 23 better MADRS scores at base -- at the end point 24 than those who were taking Prozac. 210 1 A I think that's a 2 reasonable conclusion, but I honestly don't know 3 what is meant by the MADRS score in this illness, 4 so I don't know exactly what score that refers to. 5 Q Doctor Thompson, as the 6 chief scientific officer of Eli Lilly and Company, 7 can you get us more details on this study and -- 8 to answer some of the questions that are posed by 9 this study? 10 A I will certainly do my 11 very best; I don't know what details are 12 available, but I'm certainly willing to try. 13 Q Wouldn't you expect there 14 to be more details available in hand at Lilly 15 somewhere? 16 A Probably. This is part 17 of a system which I helped implement years ago 18 called Global Project Tracking, which in fact 19 tracks all of the studies done worldwide with 20 Lilly products or of interest to Lilly, it doesn't 21 necessarily have to involve one of our products, 22 and this is sort of the standardized report that 23 we get. Now, in some cases -- and I do not know 24 the study. In some cases, in fact, there are no 211 1 more data that are within Lilly either in the 2 United States or elsewhere. Since this is an 3 international study, I presume Doctor Montgomery 4 did it at home, there may not be anything else in 5 the United States that refers to this or there may 6 be absolutely complete data with all the clinical 7 report forms, I can't tell. 8 Q If this was done for 9 Lilly, paid for by Lilly, wouldn't the clinical 10 report forms be sent to Lilly? 11 A I'm not sure it says here 12 anything -- that this was either initiated by 13 Lilly or paid for by Lilly. 14 Q We have -- testimony from 15 Doctor Beasley indicated that this was done for 16 and paid for by Lilly. And if you'll look at the 17 top of the center of the second page, that's a 18 Lilly code there -- 19 A But -- 20 Q -- is it not? 21 A Yes, sir, but we assign a 22 unique code number to every protocol that's being 23 tracked, and in fact every visit of every patient 24 being tracked worldwide, so that the existence of 212 1 that code doesn't speak to whether Lilly paid any 2 money for or has additional data. Many of these 3 studies are done in which all we furnish is the 4 drug and placebo, for example, in a blinded 5 fashion because it's so difficult for the 6 individual investigator to do that. 7 Q Doctor Thompson, Doctor 8 Charles Beasley has sworn under oath -- he's the 9 author of the meta analysis, remember him? 10 A Yes, sir. 11 Q He's sworn under oath 12 here sitting where this lady was that Doctor 13 Stuart Montgomery did this study for Eli Lilly and 14 Company, under a protocol designed by Eli Lilly 15 and Company, and he was paid by Eli Lilly and 16 Company, okay? 17 A Yes, sir. 18 Q You don't have any 19 indication that Doctor Beasley would misstate 20 something like that, do you? 21 A Oh, I'm sure Doctor 22 Beasley would not misstate anything. 23 Q So my point is, Lilly did 24 pay for this, this is a Lilly study, and certainly 213 1 Lilly has got to have more information than this, 2 wouldn't you expect, since it is a Lilly study? 3 A I would expect that 4 that's correct. 5 Q If you were still in 6 charge of this type of work, you would insist on 7 it, wouldn't you? 8 A No, sir, we had different 9 rules regarding different kinds of studies done at 10 different times with a product in different parts 11 of the world. You're asking me to make a 12 hypothetical assertion and I don't know anything 13 about the details of the study. 14 MR. SMITH: We've got a 15 document that might help you out. 16 (THOMPSON EXHIBIT NO. 5 MARKED FOR 17 IDENTIFICATION.) 18 THE WITNESS: Yes, sir. 19 Q (BY MR. SMITH) All 20 right. Exhibit -- what is it? 21 A Five. 22 Q 5, Exhibit 5 is a 23 document dated October 3rd, 1990, correct? 24 A Yes, sir. 214 1 Q And it talks about 2 Montgomery data on the top of the page, does it 3 not? 4 A Yes, sir. 5 Q If you'll look, it's 6 to -- the bottom line there is to Robert G. 7 Thompson, correct? 8 A I think that's -- 9 Q The middle line? 10 A Yes, sir, it says to 11 Robert G. Thompson. 12 Q And who is he? 13 A He's a physician that 14 used to be with Lilly. 15 Q And what was his position 16 in October 1990? 17 A I don't remember whether 18 he was an associate clinical research physician or 19 a clinical research physician, but he was one of 20 the many physicians working with Prozac and 21 similar drugs. 22 Q If you look at Point 2? 23 A Yes, sir. 24 Q It says HC 35. Now look 215 1 at the code there on Exhibit 4. It appears that 2 that's the same study that has been summarized by 3 Exhibit 4, does it not? 4 A I think so. 5 Q It says: Suicide study, 6 there have been no successful suicide attempts to 7 date. Once again my apologies for the delay in 8 getting this message to you. I believe we now 9 have some more work to do on this subject. 10 Patrick will fill me in on the details. We are 11 cleaning the data from HC 35 as fast as we can get 12 it but this is proving difficult as the -- 13 something deleted -- seems to be away most of 14 October having been in Japan for three weeks in 15 September. They have not let us have access to 16 the CRF's in the E lot this week and -- strike 17 that. They have not let us have access to the 18 CRF's in their absence but have promised to have 19 them ready for collection in two batches, E lot 20 this week -- on E lot this week and the rest after 21 October 17th. Best regards, Marilyn -- or is that 22 one lot, in two batches, one lot? I've pretty 23 well botched that batch of English, have I not? 24 MR. FREEMAN: We're not 216 1 going to count up the mistakes this time. 2 MR. SMITH: I'm not going 3 to ask him, either. 4 A There were three others, 5 but the content is right. 6 Q I haven't had as much 7 experience reading this E-mail as you have, Doctor 8 Thompson. 9 A This one is difficult 10 because it's not handling the end of lines 11 correctly, I apologize. 12 Q So apparently this is -- 13 I'm handing you Exhibit 5 just to give you further 14 reassurance that apparently this was a Lilly 15 study, that apparently data is being sent to 16 Lilly, it's being delayed obviously, as per the 17 text. 18 A I didn't question your 19 word at all when you told me that Doctor Beasley 20 had said it; I'm sure that's correct. 21 Q My question is, can you 22 get us some more information about this study -- 23 A I'll do my very best. 24 Q -- as the chief 217 1 scientific officer of Lilly? 2 A Yes, sir. 3 Q So we can visit with you 4 about it tomorrow or the next day? 5 A I will do my very best. 6 I can't guarantee how successful or the time 7 frame, but I will do my very best. 8 Q I appreciate that. 9 Obviously, that's subject to approval of your 10 lawyers. 11 MR. FREEMAN: That's 12 right. 13 Q Is there any type of 14 document retention policy at Lilly? 15 A Yes, sir. 16 Q Tell me about that, 17 please, sir. 18 A I'm not sure I can tell 19 you the exact specifics of the duration of 20 retention. It certainty complies with all of the 21 laws and regulations worldwide, but therefore it 22 may differ from country to country because, for 23 example, in Europe there are some different rules 24 and they have changed over time in terms of the 218 1 duration of retention of documents. 2 The best as I can 3 currently remember, in many European countries the 4 requirement is now seventeen years after approval 5 of the product, and in the United States, I think 6 it's -- I think it's some number of years after 7 the withdrawal of the product from the market, but 8 I'm not a good source for asking you that; we have 9 standard operating procedures. 10 Q So if a document, say a 11 case report form, comes to Eli Lilly from an 12 investigator within the United States, how long 13 will that document be kept by Eli Lilly and 14 Company? 15 A The general practice has 16 been to keep a clinical report form within the 17 United States on a trial that we sponsor for a 18 very long period of time, long after the NDA has 19 been approved. And in fact I believe that most of 20 those are saved for very long periods of time 21 after approval of the product. 22 Q All right. Let's say a 23 document is generated in a foreign country and 24 sent to the United States, for instance -- I 219 1 assume this is a study done in England, and the 2 case report forms would be sent to Lilly here in 3 Indianapolis. 4 A I wouldn't want to make 5 that assertion, sir, because we don't have a 6 standard operating procedure that all clinical 7 report forms from international studies come to 8 Indianapolis at all. 9 Q Okay. Then what data do 10 you get from your foreign affiliates in order to 11 evaluate a clinical trial done outside the United 12 States, sir? 13 A Well, there's a very wide 14 spectrum that would go all the way from getting 15 all of the clinical report forms and documents in 16 this trial to having only a summary similar to the 17 two-page one you gave me from global project 18 tracking, and it would vary from study to study. 19 Q Well, how much do you 20 suppose it would cost Eli Lilly and Company to do 21 a study by someone who is as well known in the 22 psychiatric community as Doctor Stuart Montgomery, 23 to do a study on a hundred -- in excess of a 24 hundred patients for over twenty-four weeks, how 220 1 much do you think such a study like that would 2 cost? 3 A Well, somewhere between 4 zero and more money than that, because we would 5 certainly have internal costs no matter what the 6 grants were being paid to the investigator. But 7 we have some very famous people who do studies 8 that they wish to do for no direct income from 9 Lilly, where we just pay expenses, some where they 10 pay the expenses, so I wouldn't have any idea. 11 Q Well, Lilly is sponsoring 12 this study. 13 A But as I said earlier, 14 sir, we sponsor some studies in which the only 15 thing that we really contribute is drug and 16 placebo that are blinded, and in others we pay 17 people to do studies. 18 Q From a scientific 19 standpoint, wouldn't you want to get more 20 scientific information than is included within 21 these two pages marked Exhibit 4? 22 A Oh, now that you've shown 23 me these, I have a lot of interesting questions 24 that I'd like to see the data run. 221 1 Q All right. So -- but 2 wouldn't you expect that data to be here in 3 Indianapolis? 4 A I wouldn't want to make 5 that assertion, sir. 6 Q I'm not asking for a 7 guarantee, but in a normal situation, wouldn't you 8 think there would be more data in Indianapolis, 9 Indiana than is contained on these two pages? 10 A Not necessarily. 11 Q Where would the full data 12 be? 13 A Well, they talked in here 14 about attempting to get the data, and I'm not sure 15 who Doctor or Ms. Charlesworth is, but I think 16 that's somebody at Basingstoke, so I assume when 17 they're talking about getting the data that it 18 would be at Basingstoke, and I have no idea 19 whether it was transmitted here. And you 20 mentioned specifically the clinical report forms. 21 I would assume that the electronic data images 22 might be here, but not the actual paper. 23 Q But if the electronic -- 24 electronic data images are here, that can be 222 1 brought up, can it not? 2 A If it's here, of course. 3 Q All right. I'm not 4 asking you for a guarantee that it's here, I'm 5 just asking you what the likelihood is that 6 there's more information than is contained on 7 these two pages. 8 A I wouldn't know how to 9 put a probability on it. 10 Q Would the physical 11 documentation still be in existence in 12 Basingstoke -- am I saying that right? 13 A Basingstoke. I would 14 think, yes, our standard operating procedures 15 would have those documents retained for a long 16 number of years, so since this is -- 1990, is it? 17 Q Yes. 18 A I would assume that 19 that's true. 20 Q Would the medical monitor 21 on this study have more information about this? 22 A Yes, sir. 23 Q Should he have more 24 information about this? 223 1 A Yes, sir. 2 Q Is there anything about 3 the data that you see here that's surprising to 4 you, Doctor Thompson? 5 A The dropout rate, I'm not 6 sure whether I'm surprised or not, but the 7 analysis that's provided in the last paragraph 8 really only addresses the fifty-seven patients who 9 completed the trial, and as you recall, there were 10 fifty who dropped out, and there is no information 11 about what happened with them, and I think there 12 might be very interesting data about those 13 patients and I just have no idea what happened to 14 them. I also, again, don't know how the MADRS 15 score is interpreted in personality disorder, so 16 I'm not sure what that means when it says a 17 treatment effect in favor of, whether that's the 18 total score or whether it's been scaled in some 19 fashion. 20 Q If you can see if you can 21 secure some more information for us, we'd 22 appreciate it. 23 A Yes, sir. 24 Q To be fair to everyone, 224 1 whatever the Stuart Montgomery study showed, it 2 was not a study of individuals in -- depressed 3 patients? 4 A That's what this says, 5 it's in personality disorder, nondepressed 6 patients with personality disorder. 7 Q And it does not directly 8 address the question of whether or not Prozac 9 produces suicidal ideation in individuals, does 10 it? 11 A I wouldn't make that 12 assertion at all. This is a controlled 13 prospective study in which presumably comparable 14 patients selected because of their having -- best 15 I can read it -- suicidal ideation and personality 16 disorder, randomly given either placebo or 17 fluoxetine, and I think the data speak directly to 18 whether or not the molecule fluoxetine would 19 induce suicidal behavior. 20 Q Do you believe a molecule 21 can induce behavior? 22 A Yes, sir. 23 Q Do you believe the Prozac 24 molecule can induce behavior? 225 1 A Yes, sir. 2 Q What other molecules 3 induce behavior? 4 A Many, many different 5 molecules. 6 Q Give me some examples. 7 A Well, all of the other 8 antidepressants certainly can induce different 9 kinds of behaviors because, after all, improvement 10 in depression is measured in part by what the 11 patient thinks and in part by the patient's 12 behaviors. So you have drugs that are not 13 primarily given to change a psychiatric illness 14 that also can produce behaviors. Caffeine will, 15 in some patients, produce behaviors. 16 Q Generally stimulatory 17 behaviors, nervousness, agitation? 18 A Caffeine? 19 Q Yes. 20 A It depends on how much 21 you take and how tolerant you are of it. If you 22 take a lot of caffeine every day, for example, 23 caffeine has almost no measurable effects at all 24 because of the level of tolerance. 226 1 Q Can that be said 2 generally of most medications -- 3 A No, sir. 4 Q Can that be generally 5 said of most medications, that a person's response 6 to medication depends on the amount of medication 7 they're taking and the duration for which they're 8 taking the medication? 9 A Yes, sir, I think the -- 10 yes, your assertion is correct, that the effects 11 of the medicine would be related both to the 12 amount of dose and the duration to be taken. 13 Q That can be said for most 14 medications? 15 A Yes, sir. 16 Q That's your professional 17 opinion and it's well known in pharmacology and in 18 medicine? 19 A Yes, sir. 20 Q You didn't have to become 21 a medical doctor to learn that, you knew that as a 22 Pharm.D. -- or as a Ph.D. in pharmacy, excuse me. 23 There's a difference in Pharm.D.'s and Ph.D. in 24 pharmacy. 227 1 A I don't have a Ph.D. in 2 pharmacy. 3 Q What do you have a Ph.D. 4 in? 5 A Pharmacology. 6 Q Pharmacology. There's a 7 difference in that, too? 8 A Yes, sir. 9 Q Is it generally known 10 that an individual's response to a particular 11 molecule can vary with the particular individual 12 or vary among particular individuals? 13 A Yes, sir. 14 Q In other words, you might 15 not be susceptible to caffeine, and yet it might 16 keep me awake all night, correct? 17 A Yes, sir. 18 Q You might be able to take 19 two drinks and be completely fine, I might be able 20 to have a half a drink and be acting crazy or 21 acting inappropriately or inebriated? 22 A That's possible, but 23 very, very unlikely. 24 Q If I had a particular 228 1 allergy or something to alcohol, that could be the 2 case? 3 A I'm not sure I know of an 4 allergy to alcohol, and even the most susceptible 5 patients I'm aware of wouldn't ordinarily have a 6 behavior manifestation with a half a drink. The 7 lowest blood alcohol concentration I'm aware of 8 that even in very sophisticated tests would 9 deteriorate a psychomotor task would be about 10 point oh four percent, and I don't think you can 11 get there with a half a drink. 12 MR. SMITH: Why don't we 13 change tapes and change subjects. 14 (SHORT BREAK TAKEN.) 15 (THOMPSON EXHIBIT NO. 6 MARKED FOR 16 IDENTIFICATION.) 17 MR. BOUR: This is the 18 start of Tape 3, it is 3:07. 19 Q (BY MR. SMITH) Doctor 20 Thompson, Exhibit 6 is a -- apparently a 21 meeting -- minutes of a meeting held at the Food 22 and Drug Administration on September 25th, 1990, 23 correct? 24 A Yes, sir. 229 1 Q You were present at that 2 meeting? 3 A Yes, sir. 4 Q Along with a number of 5 physicians and individuals from Eli Lilly and 6 Company? 7 A Yes, sir. 8 Q And also at the meeting 9 for the Food and Drug Administration was a number 10 of physicians and individuals? 11 A Yes, sir. 12 Q The document indicates 13 that the most prominent issue had been the 14 spectrum of suicidal behavior, does it not? 15 A Yes, sir. 16 Q It goes on to say that 17 you distinguish three categories of events of 18 particular interest: Completed suicide, suicidal 19 acts, defined broadly, and suicidal ideation. 20 That you presented data from extensive 21 premarketing studies which did not demonstrate a 22 correlation between completed suicide and Prozac, 23 correct? 24 A Yes, sir. 230 1 Q But you indicated to them 2 that you were still in the process, or Lilly was 3 still in the process of retrieving data from 4 foreign studies for additional analysis? 5 A Yes, sir. 6 Q And the issue was 7 discussed whether Lilly's large database derived 8 from clinical trials and postmarketing reports 9 were sufficient to address all outstanding issues, 10 correct? 11 A Yes, sir. 12 Q The document goes on to 13 say that the firm -- I assume that's Lilly, is 14 that correct? 15 A Yes, sir. 16 Q Contended that 17 prospective trials were hampered by the inability 18 to reach agreement with Doctor Teicher on 19 operational criteria for the phenomena referred to 20 in his article, correct? 21 A Yes, sir. 22 Q Do you know what problems 23 there were with Doctor Teicher in reaching an 24 agreement with him concerning future studies? 231 1 A Well, as best I can 2 recall, the difficulty was not as much with Doctor 3 Teicher as the fact that we couldn't find a lot of 4 other psychiatry experts who had seen similar 5 patients or could give us a crisp definition of 6 what Doctor Teicher reported in his article. 7 Q Well, Doctor Leber had 8 earlier suggested that you get with Doctor Teicher 9 and that you design a study with Doctor Teicher? 10 A Yes, sir. 11 Q And this document is 12 dated later than that suggestion? 13 A If you say so. 14 Q Do you recall what 15 specifically was done in getting with Doctor 16 Teicher in order to attempt to accomplish that? 17 A Well, I think earlier you 18 had shown me a document that talked about two of 19 our physicians flying to Boston to talk with 20 Doctor Teicher. I know that contacts were made 21 with Doctor Cole, who was one of the coauthors on 22 the paper. I know that we had gotten reports 23 about presentations that Doctor Teicher had made 24 at things like staff meetings or rounds in regard 232 1 to those patients, and we were having difficulty 2 understanding exactly the nature of those patients 3 because we had not seen very many reports that 4 were similar to them. 5 Q But Doctor Teicher never 6 told you that he would not cooperate with you in 7 further analysis of what he was seeing, did he? 8 A I'm not aware that he 9 ever said that. 10 Q And you don't know of any 11 instance where he refused to cooperate with Lilly 12 in examining this phenomenon, do you? 13 A I don't know of any 14 instance when he refused to cooperate, no. 15 Q It says two types of 16 prospective trials were discussed at the meeting 17 with Lilly -- with the FDA. A, a large two arm, 18 randomized, double blind, parallel group study 19 comparing fluoxetine and active control in 20 patients with typical depression with outcome 21 measures of completed suicides, suicidal acts and 22 suicidal ideation, correct? 23 A Yes, sir. 24 Q Was that ever done, sir? 233 1 A No, it wasn't. 2 Q B was an in-hospital 3 rechallenge of patients who met predefined 4 criteria for suicidal acts or ideation on either 5 fluoxetine or a standard tricyclic antidepressive, 6 correct? 7 A Yes, sir. 8 Q For the benefit of those 9 that might not be as sophisticated, what is a 10 rechallenge? 11 A That would ordinarily be 12 exposing the patient after an event to a similar 13 form of therapy or a controlled form of therapy 14 and seeing whether the event recurred in the same 15 fashion. 16 Q Is that accepted as a 17 valid means of investigating a phenomena of 18 whether or not that phenomena is associated with a 19 drug? 20 A It is in regard to 21 association, but it's very difficult to assert 22 causality in either direction. For example, I 23 believe that in one of my publications in the New 24 England Journal we showed that there actually is a 234 1 small population of patients who have had 2 unequivocal penicillin allergic reactions who will 3 have another reaction when given penicillin as a 4 challenge. And at the same time there have been 5 publications that have looked at positive 6 rechallenges where the same event in fact has been 7 seen in the same temporal relationship with giving 8 the same therapy, which in fact it was later shown 9 that they were not a causal relationship. So 10 although it is powerful evidence, as I think you 11 were pointing out, it is not in fact certain that 12 one can either assert positive causality or 13 negative causality on this evidence alone. 14 Q But it is powerful 15 evidence? 16 A If you saw it in a number 17 of patients, yes. 18 Q And it is something that 19 is generally accepted as powerful evidence among 20 the scientific community, even though not 21 foolproof? 22 A If you saw it in a 23 population of patients. In an individual patient 24 it's extremely difficult to know. 235 1 Q Well, that was what was 2 being proposed was examining this in a population 3 of patients, wasn't it? 4 A Yes, sir. 5 Q You weren't -- they 6 weren't suggesting, nor was Lilly suggesting that 7 just one of each patient type be examined? 8 A That's right, you're 9 correct. 10 Q In fact, it says patients 11 from both groups would be randomized to 12 fluoxetine, a standard tricyclic antidepressant or 13 placebo, and patients would be monitored for 14 reemergence of suicidal ideation or behavior, 15 correct? 16 A Yes, sir. 17 Q That was not done either, 18 was it, Doctor? 19 A No, sir. 20 (THOMPSON EXHIBIT NO. 7 MARKED FOR 21 IDENTIFICATION.) 22 Q Doctor Thompson, is 23 Exhibit 7 a document that you've reviewed in 24 preparation for your deposition? 236 1 A No, sir. 2 Q Do you recall authoring 3 Exhibit 7? 4 A Yes, sir. 5 Q It's a document authored 6 by you dated February 13th, 1991, correct? 7 A Yes, sir. 8 Q Concerning Prozac and 9 suicidality, correct? 10 A Yes, sir. 11 Q And it's -- there's a lot 12 of individuals listed on the document. Any 13 particular reason that those particular 14 individuals are listed? 15 A Most of the ones under 16 the "to" were the medical directors of affiliates 17 around the world, and most of those in the "CC" 18 were senior scientists within Lilly Research 19 Laboratories. 20 Q All right. There you 21 mentioned that you will -- you say we will 22 probably do two studies, correct? 23 A Yes, sir. 24 Q And you say -- well, let 237 1 me start back and -- to give you the full text of 2 what it says. It says: To let you know where we 3 are on depression, let me give you a brief note. 4 Primarily for the FDA, but also to nail down that 5 Prozac reduces the risk of suicidality, we will 6 probably do two studies. Correct? 7 A Yes, sir. 8 Q One, challenge study, 9 blinded prospective, in any patient we identify 10 who has the intense suicidal ideation similar to 11 that described by Teicher. Correct? 12 A Yes, sir. 13 Q That is the same 14 rechallenge as is mentioned in Exhibit 6, is it 15 not? 16 A Well, throughout this 17 period we kept struggling with how to do the 18 studies, so the same rechallenge I guess I have a 19 little problem with; we were working on how to do 20 a rechallenge type study that would be valid. 21 Q The source of my question 22 is, in Exhibit 7, under 1 you use the word a 23 challenge, correct? 24 A Yes, sir. 238 1 Q And in Exhibit 6, under B 2 it says an in-hospital rechallenge. Can those two 3 words be used interchangeably, that's simply my 4 question? 5 A I think they have 6 essentially the same meaning. 7 Q You didn't intend a 8 different meaning than is -- than in that term as 9 is used in Exhibit 6, did you not? 10 A Well, there is a very 11 subtle distinction there, and that is that if you 12 read Exhibit 7, that challenge might occur to a 13 patient who had had the intense suicidal ideation 14 on any former therapy, including even not drug 15 therapy, so they would then be challenged for the 16 first time by Prozac or control, whereas 17 rechallenge has more of the sense -- and you see 18 it says down here, in-hospital rechallenge who met 19 predefined criteria for suicidal acts or ideation 20 on either fluoxetine or standard tricyclic 21 antidepressant. So there's a very subtle 22 distinction there. 23 Q But the basic science is 24 the same in that you're going to examine a patient 239 1 to see if they -- if a particular act or 2 occurrence recurs -- 3 A Yes, sir. 4 Q -- following the 5 administration of a particular drug? 6 A Yes, sir. 7 Q Was that study done, as 8 mentioned in -- 9 A No, sir. 10 Q The No. 1 study mentioned 11 in Exhibit 7? 12 A No, sir. 13 Q You mention also a 14 prospective study using new instruments to measure 15 suicidality in depressed folks randomly given 16 Prozac versus placebo on active comparator, 17 correct? 18 A There's a line cut off of 19 the copy that I've got, but assuming you're 20 reading it correctly, I guess that's correct. My 21 second page has on it -- the first line is -- 22 MS. ZETTLER: Take a look 23 at that one, Doctor. 24 A Yes, that's better. Yes, 240 1 that helps. Yes, sir. Excuse me for separating 2 the page. 3 Q All right, now that 4 you've got the entire document in front of you, 5 Doctor, it appears that the second item that you 6 suggested be done to nail down that Prozac reduces 7 the risk of suicidality would be a prospective 8 study using new instruments to measure suicidality 9 in depressed folks randomly given Prozac versus 10 placebo or active comparator, correct? 11 A Yes, sir. 12 Q Was this study done? 13 A No, sir. 14 Q When you use the term 15 prospective study, to what do you refer? 16 A That the patients would 17 be enrolled and treated after the study was 18 designed. 19 Q With the specific 20 objective to measure suicidality under this 21 formula? 22 A Well, that doesn't have 23 anything to do with prospective, per se, as a 24 design strategy, but what's talked about in 2 241 1 would be specifically with that objective in mind, 2 yes. 3 Q You enroll the patients, 4 then you treat them and you look specifically at 5 whether or not there is an emergence of 6 suicidality, right? 7 A Yes, sir, that's what's 8 described in No. 2 here. 9 Q And that was not done? 10 A That was not done. 11 Q By Lilly? 12 A By Lilly. 13 Q You use the term here 14 using new instruments to measure suicidality? 15 A Yes, sir. 16 Q To what do you refer, 17 sir? 18 A That we were attempting 19 to validate instruments that were new, not 20 accepted at the time that I wrote this memo, that 21 might be more sensitive or specific in the 22 recognition of suicidality. 23 Q Specifically what were 24 those new instruments? 242 1 A We worked with at least 2 one expert who had worked most of his career with 3 suicidality to try to develop and validate a new 4 instrument. 5 Q Are you talking about 6 Doctor Beck? 7 A You asked before who it 8 was, and that's a possibility. I can't remember 9 exactly who it was. 10 Q Doctor Ivan Miller? 11 A I'm sorry, I don't 12 remember who it was specifically. 13 Q Who do you recall was 14 responsible for working with that individual, 15 whoever it was? 16 A Well, it would be one of 17 a team of psychiatrists, but I don't know which 18 one was specifically responsible for that task. 19 Q It would be someone in 20 Doctor Zerbe's group? 21 A Yes, sir. 22 Q The third suggestion that 23 you make that Lilly do to nail down that Prozac 24 reduces the risk of suicidality would be, 3, 243 1 probably use fluoxetine as an active comparator in 2 many of the studies of new antidepressants. This 3 would then serve as additional suicidality studies 4 for the FDA. We'd probably want to use fluoxetine 5 in studies without placebo controls and possibly 6 when there is also a tricyclic control. Correct? 7 A Yes, sir. 8 Q Was that done? 9 A I think some of the 10 ongoing studies with other antidepressants did use 11 fluoxetine as a -- one of the arms of the therapy. 12 Q Studies done by Lilly or 13 studies done by other firms examining other 14 antidepressants? 15 A Both. 16 Q What studies did Lilly 17 do -- 18 MR. FREEMAN: Wait. 19 Q -- where Prozac was used 20 as an active comparator? 21 MR. FREEMAN: Before you 22 answer, Doctor Thompson, be careful not to 23 disclose the identity of any compounds under 24 investigation which are not marketed, don't 244 1 disclose them by name. 2 MS. ZETTLER: He can tell 3 us what the general action of the drug is, 4 et cetera. 5 MR. FREEMAN: You can 6 tell them what the therapeutic class is. 7 A I don't know the specific 8 details of the studies. That was a general 9 strategy to be employed because of the enormous 10 difficulty in studying enough patients where one 11 could, in fact, make a valid conclusion about the 12 incidence of suicidality. 13 Q But you don't know for 14 sure that that was even done using Prozac as a 15 comparator with other antidepressants? 16 A I told you I thought that 17 it had been done, I'm not sure. 18 Q But you're not certain? 19 A That's correct. 20 Q And you certainly don't 21 know what the results of any of those studies 22 were, do you? 23 A No, I do not know the 24 specific results. 245 1 Q Do you know whether or 2 not any of those other studies of other 3 antidepressant used other measurements of 4 suicidality, that is other scales to measure 5 suicidality other than the HAMD? 6 A Or the MADRS scale. 7 Q Or the MADRS. 8 A I don't believe that any 9 of those in fact did because I don't believe we 10 ever validated an alternative scale or found one. 11 Q Well, do you know whether 12 a competitor may have done so? 13 A No, I don't know that of 14 my own knowledge. 15 Q What would be necessary 16 to validate a scale used to measure suicidality? 17 A Well, there's a number of 18 different ways that we use the word valid in terms 19 of qualifying scales. There, for example, is face 20 validity, which is generally accepted to mean that 21 rational scientists who are knowledgeable in the 22 field would look at the instrument and say that it 23 should measure the right thing. There's content 24 or context validity where one tests one's scale 246 1 against another as best one can, so that, for 2 example, if you took a large number of people who 3 through other measures had been shown to have 4 suicidal ideation or gestures or acts or actions, 5 and then used the scale and found that you could 6 differentiate those individuals from people who 7 weren't having suicidal ideation by the use of the 8 scale by some scoring system, then that would be a 9 way of actually using content validity for the 10 scale. 11 Q But that's not been done? 12 A We never were able to do 13 that because of the difficulty of achieving that; 14 that's correct, it has not been done. 15 Q Because it's too 16 difficult, is that right? 17 A Yes, sir. 18 Q Has anybody ever 19 explained to you or do you know what the 20 difficulty is in examining such a -- in validating 21 such a scale? 22 A Yes, I've been part of a 23 number of discussions as we worked very hard to 24 try to in fact accomplish that goal, and -- 247 1 Q Do you think it will ever 2 be accomplished? 3 A It will be very difficult 4 to do and it will take a long period of time to do 5 it. 6 Q Is that work ongoing? 7 A I don't know how actively 8 Lilly is pursuing that at this time. 9 Q That's what I mean. 10 A That's not what you 11 asked. 12 Q I understand that. 13 A I don't know how actively 14 Lilly is pursuing that goal at this time. 15 Q Do you know if they're 16 pursuing it at all? 17 A I do not know that for 18 sure. 19 Q Who would know that? 20 A Oh, I think Doctor 21 Tollefson would probably be the person I would 22 ask. 23 MR. SMITH: Make a note 24 to ask Doctor Tollefson that when we talk to him 248 1 next week. 2 Q Why couldn't you use some 3 existing scale already in existence to validate a 4 new scale? 5 A You could. Of course, we 6 had a great deal of experience with both the 7 Hamilton depression scale and the MADRS scale. 8 Q But you knew that the 9 Hamilton depression scale had never been validated 10 for suicidality, didn't you? 11 A Well, I don't think 12 that's a fair assertion since that question on the 13 Hamilton depression scale, to my knowledge, has 14 not been questioned as a valid measure of 15 suicidality. 16 Q Well, it's not been 17 validated either, has it? I mean, nobody has 18 taken the Hamilton depression scale and compared 19 it with a scale specifically designed to measure 20 suicidality to see whether or not the Hamilton 21 depression scale predicted suicide in the same 22 manner that one of these scales specifically 23 designed to measure suicidality had? 24 A Well, but, sir, what 249 1 you're asking is circular reasoning. What you 2 asked was had this Hamilton depression scale been 3 validated against a new scale, which of course 4 would both validate the new scale and the Hamilton 5 depression scale, so it's sort of circular 6 reasoning. 7 Q Then why not do it? 8 A Well, we were working to 9 try to find a new scale that on face validity 10 would be thought by psychiatrists who are expert 11 in this area to be any better than the Hamilton 12 depression scale and the MADRS scale, and as hard 13 as we worked and as many people as we talked to, 14 no one felt that we had a scale that was any 15 better and that we had enormous data collection 16 that was highly valid using those two highly 17 validated scales. 18 Q Well, in fact you 19 submitted a proposed protocol examining this issue 20 to the Food and Drug Administration with a scale 21 attached to it, didn't you? 22 A I don't remember. 23 (THOMPSON EXHIBIT NO. 8 MARKED FOR 24 IDENTIFICATION.) 250 1 Q Doctor Thompson, you are 2 certainly free to read the entire text of that 3 document. I'll tell you, though, I'm not 4 intending to ask you specific questions about a 5 lot of details on it, and I'm going to point you 6 to the areas that I want to discuss with you, if 7 that will help you, but you are certainly free to 8 read any portion or all of it. 9 A Yes, sir. 10 Q Have you seen Exhibit 10 11 (sic) before -- 12 A I don't believe so. 13 Q -- Doctor Thompson? This 14 is not a document you reviewed in preparation for 15 your deposition here today? 16 A No, sir. 17 Q Exhibit 10 is a 18 document -- 19 A You mean Exhibit 8, sir? 20 Q Yes, Exhibit 8 is a 21 document that is dated March 29th, 1991, authored 22 by Doctor M.W. Talbott, Ph.D., is it not? 23 A Yes, sir. 24 Q And Doctor Talbott at 251 1 that time was the Director of Medical Regulatory 2 Affairs for Eli Lilly and Company, was he not? 3 A Yes, sir. 4 Q The cover letter states 5 that we are submitting a draft protocol entitled 6 "Fluoxetine/Desipramine/Placebo Rechallenge Study 7 in Patients Who Developed Suicidal Ideation While 8 Under Treatment," does it not? 9 A Yes, sir. 10 Q And it does indeed submit 11 a draft protocol -- 12 A Yes, sir. 13 Q -- to the Food and Drug 14 Administration. And the purpose for him 15 submitting this to the Food and Drug 16 Administration was so they could consider it, was 17 it not? 18 A Yes, sir. 19 Q It was under 20 consideration at Lilly? 21 A Yes, sir. 22 Q This was something that 23 the Food and Drug Administration had asked that 24 Lilly do? 252 1 A Well, asked you would 2 have to define very broadly. Lilly primarily, and 3 certainly the FDA agreed, wished that we had some 4 way of prospectively addressing this issue of 5 emergence of suicidality, and I think that Lilly 6 was struggling with how, in fact, to logistically 7 carry out a scientifically valid study, but we 8 were never -- we were never commanded by the FDA 9 to do a study, either this study or any other 10 study. 11 Q Well, you submitted a 12 plan that you were considering to address this 13 issue, were you not? 14 A Yes, sir. 15 Q That's Exhibit 8, 16 correct? 17 A Yes, sir. 18 Q And it has with it a 19 scale for suicide ideation, does it not? 20 A Yes, sir. 21 Q And that scale has 22 twenty-one questions, does it not? 23 A Yes, sir. 24 Q The Hamilton depression 253 1 scale has one question on -- for a measurement of 2 suicidal ideation, does it not? 3 A Actually, this protocol 4 talks about the HAMD twenty-eight-question scale, 5 and I don't think I've seen that. I'm only 6 familiar with the twenty-one question version 7 which has one question which addresses it 8 specifically. So I'm not sure what's in the other 9 seven questions that I don't think I've ever seen. 10 Q Nobody has ever come up 11 with a Hamilton depression scale that has any 12 questions on suicide other than Item 3, Doctor 13 Thompson, all right? 14 A Thank you. 15 Q So the answer to my 16 question would be the Hamilton depression scale 17 has one question on suicide, this scale for 18 suicidal ideation that Lilly has submitted to the 19 Food and Drug Administration has twenty-one 20 questions, doesn't it? 21 A Yes, sir. 22 Q Would it be reasonable to 23 assume that this scale is going to secure more 24 information concerning a particular patient's 254 1 general suicidal ideation than the HAMD Item 3? 2 A I think it would secure 3 more information about it, yes. 4 Q This was in fact not a 5 new scale, was it? 6 A I don't really think I've 7 seen this scale before, so I don't know much more 8 than what's on these page about it. 9 Q Well, I don't really know 10 that much either, Doctor Thompson, but I see here 11 where it was copyrighted by Aaron T. Beck, MD, in 12 1979 on the last page. Do you see that? 13 A Yes, sir. 14 Q So I would assume from 15 that that this scale has been in existence since 16 1979. 17 A I would agree with that 18 assumption. 19 Q And was in existence at 20 the time Lilly was conducting most of their Phase 21 III and IV clinical trials, was it not? 22 A Yes, sir. 23 Q Do you know if anybody at 24 Lilly contacted Doctor Beck concerning 255 1 administering this scale to individuals in the 2 Prozac, fluoxetine clinical trial for depression? 3 A Well, I think Doctor Beck 4 was among the suicidality expert psychiatrists 5 that we consulted, yes. 6 Q Do you know if anybody 7 ever asked him whether or not it would be 8 appropriate to use his scale for suicidal ideation 9 in the clinical trials done on Prozac for 10 depression back in the early '80s, since it was in 11 existence at the time? 12 A I didn't join Lilly until 13 April 1 of 1982, so I wouldn't have any knowledge 14 of what went on vis-a-vis back before then. 15 Q Have you ever seen 16 documents concerning a request to use Doctor 17 Beck's scale in the clinical trials on Prozac for 18 depression? 19 A At any time? 20 Q Yes. 21 A I believe Doctor Beck was 22 one of the experts that we consulted after the 23 publication of the Teicher report. I'm not aware 24 that we consulted him before that time. 256 1 Q Before this issue came 2 up, nobody had ever talked, as far as you know, to 3 Doctor Beck about employing his scale in your 4 clinical trials on Prozac? 5 A As far as I know. 6 Q To specifically measure 7 suicidal ideation? 8 A Well, you're then 9 implying an assertion that this scale is more 10 specific. Earlier you said would we collect more 11 information. I agreed with the assertion that 12 this would have more information, but I do not 13 necessarily agree that it is more specific. 14 That's a very tightly defined and nonambiguous 15 scientific term. 16 Q Would you agree with me 17 that probably, whether or not this scale is better 18 than the HAMD-3 scale, is something that is beyond 19 your expertise, Doctor Thompson? 20 A No, if you show me the 21 receiver operating characteristics of those two 22 tests, I can tell you with some definitive 23 knowledge as to which one is more specific. 24 Q The receiver operated 257 1 test? 2 A The receiver operating 3 characteristics of a test, yes. 4 Q Okay. Well, do you know 5 if anybody has ever looked at the receiver 6 operating characteristics of Doctor Beck's 7 twenty-one-point scale? 8 A No, sir, I'm not aware of 9 that. 10 Q Well, then you don't know 11 whether this is better -- a better or worse scale 12 for measuring suicidal ideation than the HAMD-3, 13 do you? 14 A I do not know, and that's 15 exactly what I stated; I wasn't comfortable with 16 the assertion that it was more specific. 17 Q Did you review this scale 18 before it was submitted to the Food and Drug 19 Administration as part of this proposed draft 20 rechallenge protocol, Doctor Thompson? 21 A No, sir, I said earlier 22 that I don't think I've seen it before. 23 Q Today is the first day 24 you've ever seen it? 258 1 A To the best of my 2 knowledge. 3 Q You are the chief 4 scientific officer for Eli Lilly and Company? 5 A Yes, sir. 6 Q Have you ever seen this 7 protocol before, this draft protocol? 8 A No, sir. I think, in 9 fact, I've seen the introductory pages that talk 10 about the epidemiological difficulty for the 11 design of trials, or at least we've had very many 12 discussions on this subject matter, so I may have 13 seen that. I don't think I've seen this 14 particular draft protocol before. 15 Q So you couldn't tell us, 16 as the chief scientific officer right now, in 17 looking at this protocol, as to whether or not it 18 would be sufficient to examine the issue presented 19 since you haven't seen it? 20 A But you just allowed me 21 to read it, sir, so I do have a scientific 22 opinion. 23 Q All right, what is that 24 opinion? 259 1 A Well, assuming that the 2 statistical statements in here about the power are 3 correct, and assuming that in fact this study 4 could be done, which is an important assumption, I 5 think that in fact this would have important 6 information both in terms of the cross validation 7 of the Hamilton depression scale and this new 8 scale, whatever it is, the Beck scale, and I think 9 it would provide some important information about 10 the issue. 11 Q But this protocol was 12 never done by Lilly? 13 A We never found a way in 14 which we could carry out this protocol, that's 15 correct. 16 Q You could draft a 17 protocol, but you couldn't carry it out, is that 18 what you're saying? 19 A Yes, sir. 20 Q But you think this 21 protocol presents a reasonable approach to 22 analyzing the problem? 23 A Yes, sir, I was -- in 24 reading it, I was pleased with the description of 260 1 the design and the caveats about it, et cetera. 2 If we had been able to -- 3 Q It's a Lilly protocol. 4 MR. FREEMAN: Let him 5 finish his answer, please. 6 A I don't have any fault 7 with the protocol design, but I do understand what 8 some of the limitations are in logistically 9 carrying it out. 10 Q Well, you say this is the 11 first time you've seen this protocol? 12 A I think what I said was 13 that I think I have seen the introductory page 14 which discuss the approach to the study. I am 15 fairly sure I have not seen this specific 16 twenty-one-question scale before, and I don't 17 think I've seen the protocol. I've certainly been 18 present in discussions about the design, but I 19 don't think I've seen this specific document 20 before. 21 Q Do you normally read your 22 mail or materials directed to you by individuals 23 on your staff? 24 A I read some of it. I at 261 1 least scan the face sheet of most of it, but I 2 receive a great deal of mail and much of it I do 3 not read. 4 (THOMPSON EXHIBIT NO. 9 MARKED FOR 5 IDENTIFICATION.) 6 THE WITNESS: Yes, sir. 7 Q Exhibit 9 indicates that 8 you did, in fact, receive a copy of the 9 rechallenge protocol back in April of 1991, does 10 it not? 11 A Yes, sir. 12 Q So this wasn't the -- 13 today wasn't the first opportunity that you had 14 been given to review the rechallenge protocol, 15 correct? 16 A Assuming that Doctor 17 Beasley's memo of April 17th refers to this 18 document labeled Exhibit 8, I would say that I 19 obviously had the opportunity to go and see it at 20 any time that I wanted to. What I had said before 21 was that I don't believe that I had, in fact, seen 22 the document before. 23 Q Were you not interested 24 in the protocol, was that the reason you hadn't 262 1 reviewed it? 2 A No, sir, I'm very much 3 interested in science in general and a lot of 4 Lilly business, but we have an enormous number of 5 protocols on an enormous number of drugs, and I 6 have to spend my time in the best fashion I 7 possibly can. 8 Q Well, don't you think 9 examining the issue of whether or not Prozac 10 caused suicidality in a particular individual 11 would be a pretty important issue to examine? 12 A I think it would be a 13 very important issue to examine, but I think that 14 there were one, two, three, four, five, six, 15 seven, eight, nine, ten, eleven, twelve other 16 experts addressed on this issue. Many of them are 17 psychiatrists and many of them are far more 18 familiar with this issue than I, and so I'm not 19 sure what I could have contributed at this stage 20 of the discussion. 21 Q Tell me who on there is a 22 better scientist than you, Doctor Thompson? 23 A There are many people who 24 are far more knowledgeable about psychiatry. 263 1 Q I didn't ask you that. I 2 said tell me on there who is a better scientist 3 than you, sir. 4 A Across all of scientific 5 domain? 6 Q Yes. 7 A Well, I have enormous 8 respect for virtually everyone that's on here, 9 sir. 10 Q Okay, are they all better 11 scientists than you? 12 A I think all of them are 13 very excellent scientists. 14 Q Better than you, sir? 15 A I don't know how to make 16 that measurement, sir. 17 Q Don't you think you're as 18 capable as they are in seeing the design and 19 manner of a particular clinical trial for a 20 particular subject? 21 A No, sir. 22 Q Okay, who is more capable 23 than you on this list in examining the protocol? 24 A Doctor Dorenseif and 264 1 Doctor Greg Enas are truly world class 2 statisticians who are far better than I in 3 determining the power of the statistical tests or 4 the specific statistical test to apply to these 5 kinds of data. Doctor Heiligenstein is an eminent 6 psychiatrist. Doctor Wheadon is a eminent 7 psychiatrist. Doctor Zerbe is an extremely well 8 respected CNS physician. I would say those had 9 more knowledge than me about the psychiatric 10 issues involved, and probably a lot of direct 11 knowledge about the suicidality scale which I 12 certainly didn't. Doctor Kotsanos is an extremely 13 well trained epidemiologist and in terms of the 14 epidemiology issues that were raised, he would be 15 very much involved. Doctor Jan Potvin is an 16 excellent person in terms of making sense out of 17 complex protocols. 18 Doctors Masica, Bob 19 Thompson, Allan Weinstein, although not 20 psychiatrists, were probably spending a great deal 21 more time than I with this specific issue and were 22 far more knowledgeable. Charley Sampson is 23 probably the most erudite statistician I've ever 24 met, and I would certainly trust his judgment in 265 1 terms of the statistical design. Doctor Al Webber 2 was an expert in the regulatory affairs issues. 3 So each one of these people had a great deal to 4 contribute to this and in their areas at least 5 were far better than I in terms of making a 6 contribution. 7 Q But you were in charge of 8 them all, weren't you? 9 A At least most of them. 10 But what does being in charge of mean? I'm also 11 licensed to practice any kind of medicine, but I 12 don't think you'd pick me to operate on your 13 brain. 14 (THOMPSON EXHIBIT NO. 10 MARKED FOR 15 IDENTIFICATION.) 16 Q Have you seen Exhibit 10 17 before, Doctor Thompson? 18 A I think I've seen it 19 before. 20 Q You are an addressee on 21 the document, are you not? 22 A Yes, sir. 23 Q Is this a document that 24 you reviewed in preparation for your deposition? 266 1 A No, sir, I don't believe 2 so. 3 Q This is a document dated 4 May 15, 1991 and is authored by Doctor Kotsanos, 5 is it not? 6 A Yes, sir. 7 Q And Doctor Kotsanos is 8 the well qualified epidemiologist that you 9 mentioned earlier? 10 A Yes, sir. 11 Q Apparently, with respect 12 to Exhibit 9, the draft rechallenge protocol has 13 been submitted to the Food and Drug 14 Administration, correct? 15 A Exhibit 8 do you mean? I 16 think that was the submission. 17 Q Yes, it's 8, I'm sorry. 18 A Yes, sir. 19 Q It's been submitted to 20 the Food and Drug Administration, and Doctor 21 Talbott, in his letter, requests a meeting, does 22 he not? 23 A Yes, sir. 24 Q And is this May 15th -- 267 1 actually the meeting was on May 13th in response 2 to Doctor Talbott's request for a meeting on the 3 subject? 4 A As best I can remember. 5 Q You were there? 6 A I was? 7 Q You weren't? 8 A I don't remember. 9 Q You don't remember being 10 at the Food and Drug Administration to discuss the 11 rechallenge protocol on May 13, 1991? 12 A Not specifically. 13 Q You had several meetings 14 at the FDA to discuss this issue, though? 15 A Yes, sir. 16 Q And you attended some of 17 those? 18 A Yes, sir. 19 Q This may have been one, 20 you just don't recall being there? 21 A It could have been one, 22 but I don't have any direct recollection of it. 23 Q You are at least one of 24 the individuals who is listed as a recipient of 268 1 the memo? 2 A Yes, sir. 3 Q Doctor Kotsanos says that 4 at the FDA meeting, Lilly agreed to do the 5 following projects, does he not? 6 A Yes, sir. 7 Q It says, number one, 8 proceed with the rechallenge study, correct? 9 A Yes, sir. 10 Q Lilly didn't do that, did 11 they? 12 A Well, we sure proceeded 13 with it in the sense of trying to do it, but we 14 were never able to in fact figure out a way to 15 actually get it accomplished. 16 Q Well, did you have the 17 rechallenge protocol ready to go by September 1st, 18 1991 and provide data after the first quarter 19 which would provide information on six months of 20 experience? 21 A I don't think the 22 protocol was ever actually launched in the sense 23 of patients being enrolled under it; the best of 24 my recollection is we never enrolled a patient on 269 1 the protocol. 2 Q Do you know why Doctor 3 Kotsanos would reflect in his notes that you 4 agreed to have the protocol ready to go by 5 September 1st, 1991 and provide data on six months 6 of experience? 7 A Well, I think that was 8 not an unreasonable expectation in May of 1991, 9 but we in fact propose a number of protocols which 10 are not doable and in fact never get done. I 11 mean, that's not unusual. 12 Q What about that protocol 13 is not doable? 14 A Finding the investigators 15 and patients in sufficient number to in fact be 16 able to do a study that would have any validity. 17 Q What's the number of 18 patients called for in the protocol? 19 A Two hundred. 20 Q All right. How many 21 patients did Doctor Stuart Montgomery enroll? 22 A Those are different 23 patients, sir. 24 Q I know that, but I'm 270 1 just -- they were individuals who had had suicidal 2 ideation, weren't they? 3 A There were fifty-seven 4 patients who completed the study and fifty others 5 who dropped out. 6 Q And there was -- so how 7 many were enrolled? Feel free to look at the 8 document. 9 A A hundred and seven 10 patients. 11 Q All right. So Doctor 12 Montgomery was able to find some patients who had 13 had suicidal ideation, was he not? 14 A But the protocol doesn't 15 ask for some patients with suicidal ideation; the 16 protocol criteria are far more explicit than that. 17 Q I understand that and I'm 18 not implying that, but is it your testimony here 19 that the reason that the rechallenge protocol 20 wasn't done, Doctor Thompson, was you couldn't 21 find enough patients who met the inclusion 22 criteria? 23 A You are exactly correct. 24 Q What was done to find the 271 1 those patients? Tell me specifically who did what 2 in order to recruit those patients. 3 A Some of our expert 4 psychiatrists talked to a number of potential 5 investigators, discussed the protocol with them, 6 and asked them to estimate how many patients they 7 might reasonably expect to see who would be good 8 candidates for enrollment in this protocol. 9 Q Who were the prospective 10 investigators that were talked to? 11 A I'm sorry, I don't know 12 specifically who. 13 Q Who would know that? 14 A The investigators that 15 were listed on the protocol; I think there were at 16 least six names there that were listed as 17 monitors, including -- let's see, we have five 18 psychiatrists and an MD Ph.D. 19 Q Where are they listed? 20 A I'm sorry, on Exhibit 8. 21 Q Uh-huh. 22 A Under name and title, 23 this is on page one, two, three, exhibit (sic) and 24 title of the person responsible for monitoring the 272 1 conduct and progress of the clinical 2 investigations. You have the names of five 3 psychiatrists and Doctor Dave Goldstein, who is an 4 MD Ph.D. 5 Q Okay, Doctor Beasley is 6 the -- going to be the medical monitor, right? 7 A I think this says all six 8 of them were going to be responsible for 9 monitoring the project. We tend not to use the 10 word medical monitor at Lilly, and I would -- 11 Q You don't? I've heard it 12 used by about six different Lilly employees who 13 claim to be medical monitors. 14 A Excellent. 15 Q Including Doctor Paul 16 Stark, who doesn't have an MD degree. Do you know 17 Doctor Stark? 18 A Absolutely. Was that a 19 question I was supposed to answer in some 20 fashion? 21 Q No, I said do you know 22 Doctor Stark. 23 A And I answered that. 24 Q And I believe you 273 1 answered my question. 2 Doctor C.M. Beasley is a 3 Lilly employee? 4 A Yes, sir. 5 Q Doctor D.J. Goldstein is 6 an outside investigator, is he not? 7 A No, sir, that's David 8 Goldstein. He's an MD Ph.D. who is a full-time 9 Lilly employee. 10 Q That's not the Goldstein 11 in Miami, Florida that had done some investigation 12 for you? 13 A He's Dave Goldstein who 14 works down at Lilly, down the street. 15 Q Doctor Heiligenstein 16 works for Lilly? 17 A He's a psychiatrist full 18 time at Lilly. 19 Q Doctor Lemberger works 20 for Lilly? 21 A Psychiatrist full time at 22 Lilly. At that time; he's retired now. 23 Q Doctor Street? 24 A Jamie Street, again CNS 274 1 trained, I think she's actually Boarded in 2 neurology, who works full time at Lilly. 3 Q And David Wheadon? 4 A A psychiatrist who at 5 that time worked full time at Lilly. 6 Q But these are Lilly 7 employees? 8 A Yes, sir. 9 Q I want to know the names 10 of the investigators that you talked to. 11 A No, sir, your question 12 going back to that was you asked me who they were; 13 I told you I couldn't tell you. Then you asked me 14 who at Lilly would in fact be able to know, and I 15 said the six people who were addressed on the 16 protocol. That's what I answered and that's 17 exactly what I assert, that these six people would 18 know who they talked to. 19 Q You don't know the names 20 of any potential investigators? 21 A Not of my own knowledge, 22 no, sir. 23 Q Did they report to you 24 who they had talked to? 275 1 A Well, I know that they 2 talked to a large number of people, but I don't 3 remember the names of anybody that they talked to 4 specifically, no, sir. 5 Q Were you getting reports 6 from them concerning the progress they were making 7 in selecting investigators? 8 A Yes, sir. 9 Q And it was just dismal? 10 A That's your word, 11 dismal. I think that we had a great deal of 12 difficulty finding qualified investigators who 13 felt that they could find any patients, much less 14 a substantial number of patients, who fulfilled 15 the criteria of this protocol. 16 Q What about the criteria 17 of the protocol -- and Lilly drafted the protocol, 18 right? 19 A Yes, sir. 20 Q What about the protocol 21 criteria was so difficult -- made it so difficult 22 to find patients to meet? 23 A There actually were a 24 whole number of things about the protocol that 276 1 made it very complicated. 2 Q I guess you would have to 3 look under patient inclusion and exclusion if you 4 are selecting patients, wouldn't you? 5 A No, sir, that's only a 6 part of the difficulty because the rigor with 7 which the patients were going to be treated and 8 the question of whether or not they needed to be 9 hospitalized and the question of whether or not 10 they would agree to long-term hospitalization, 11 when at the time of entry into the protocol they 12 may well not have a suicidal intent. That was an 13 extremely important issue about being able to 14 conduct the study. 15 Q I thought that the 16 subjects of the protocol were going to be 17 individuals who had experienced suicidal ideation 18 while on antidepressant therapy in the past? 19 A In the past, that's my 20 understanding. 21 Q Okay. 22 A At the time that they 23 were to enroll in this study, there was a major 24 ethical issue, since the study was designed to 277 1 look at the emergence of suicidal ideation, 2 gestures, acts and intent -- acts of suicide, 3 whether or not to protect the patients they should 4 be hospitalized. If in fact the ethical decision 5 was made that to protect the patient they'd have 6 to be hospitalized, then the patients would have 7 to agree to long-term hospitalization beginning at 8 a time when in fact that they did not have any 9 suicidal ideation or act. 10 Q Okay. The patients that 11 were going to be included in the trial were 12 individuals who had experienced suicidality, and 13 by that I mean acts or serious thoughts -- what 14 does it call for in the protocol? 15 A It says such ideation 16 developed within six months of entry into the 17 study. 18 Q All right. 19 A Substantial ideation as 20 resolved at the time of entry. 21 Q All right, and would that 22 ideation that had occurred in the past have had to 23 have been ideation for patients who were on 24 Prozac? 278 1 A No, I don't believe so, 2 let me check. During treatment with either 3 fluoxetine tricyclic antidepressant or 4 maprotiline, the patient developed in the clinical 5 opinion of a treating psychiatrist substantial 6 suicidal ideation with or without an act, 7 characterized by all of the following -- this is 8 another very important issue in terms of finding 9 patients -- a quantum, slash, extreme increase in 10 severity -- so it wasn't just that they had a 11 wondering brief moment of thinking about 12 suicide -- method, parentheses, S, contemplated 13 were violent and/or active -- so violent would 14 suggest to me that if they thought of suicide but 15 they were going to use pills, that wouldn't really 16 make it violent -- and that they had -- this is, 17 remember, all of the following features. The 18 third one was they were considered obsessive 19 and/or ego-dystonic. 20 Now, the problem that you 21 mentioned earlier is I think really the central 22 issue here, and that yes, Stuart Montgomery was 23 able to find a population of patients who 24 fulfilled a broad definition of having had 279 1 suicidal ideation. This is an extremely explicit 2 group of patients to try to mirror the patients 3 that Doctor Teicher had talked about. 4 Q But the point is that 5 that protocol and that explicit definition of 6 patients was something that was called for by 7 Lilly? 8 A In consultation with both 9 the FDA and a large number of experts in 10 psychiatry and suicidality, both in the United 11 States and internationally. 12 Q You mean that the FDA and 13 Lilly and a large number of consultants were able 14 to construct a protocol that would examine -- 15 adequately examine the issue, but there wasn't any 16 patients that fulfilled the criteria? 17 A I didn't say that there 18 were no patients that fulfilled the criteria. If 19 you recall in the discussion of the protocol, it 20 brought out the of issue of how many patients 21 would be treated by each individual investigator, 22 because statistically one needs to have more than 23 a single or even a small number of patients by 24 each investigator to be able to adequately test 280 1 inter-investigator differences, which have some 2 bearing on how to interpret the overall 3 statistical results. So what was required by this 4 protocol and stated explicitly in how it was to be 5 analyzed was a series of investigators who would 6 be able to enroll more than one or two patients 7 who fulfilled these criteria, who in fact also 8 could complete the study, because if you recall, 9 the primary analysis listed first, as I recall it, 10 was completers. There was a secondary statement 11 of doing an intent to treat analysis. And that 12 was the sticky point, as I was told over and over 13 again, that we could find some psychiatrists who 14 said that they were comfortable with the design of 15 the protocol, we could even find some who said 16 they might be able to find one patient who in fact 17 fulfilled the protocol criteria, but we couldn't 18 find any substantial number of investigators who 19 said, yes, I can probably find four or six or 20 eight of these people in a year or two. 21 Q Did you talk with anybody 22 that is in the business of administering CNS 23 clinical trials? 24 A I personally -- except 281 1 for talking with some of the consultants when they 2 were visiting Lilly, I personally did not talk to 3 potential investigators in this study. It was 4 reported to me by the individuals we talked about 5 at Lilly that in fact they had spent a great deal 6 of time trying to find potential investigators, 7 and I know how hard they worked at doing that, 8 both in the United States and internationally. 9 Q How do you know how hard 10 they worked at doing that? 11 A Because they told me how 12 hard they had worked. This was a key issue at 13 Lilly; Lilly was very intent on doing this study. 14 We all felt that in fact this study would 15 probably, our best guess was, show that 16 suicidality was reduced by Prozac in a controlled 17 study. We very much wanted the results of this 18 study. 19 Q But you couldn't get 20 enough patients and investigators together to do 21 it? 22 A That certainly isn't 23 unique with this protocol, sir. That's happened, 24 I think, a number of times since I've been at 282 1 Lilly with other drugs and with Prozac. 2 Q So is the answer to my 3 question no, we couldn't get enough patients and 4 investigators together? 5 A The answer is no, we 6 could not find enough investigators who felt that 7 they could enroll enough patients to make the 8 study valid. 9 Q But you can't, as we sit 10 here, tell me the names of any investigator that 11 was approached? 12 A No, sir. 13 Q Specifically who 14 approached any particular investigator? 15 A No, sir. 16 Q Or what efforts directly 17 were made to secure an investigator with a 18 sufficient patient population? 19 A No, sir, I can tell you 20 about that, that it was reported to me by these 21 people, including the six that were named in the 22 protocol, that considerable effort had been 23 expended in talking to a large number of potential 24 investigators who were, on their academic 283 1 credentials, well qualified, both in the United 2 States and internationally, and that the uniform 3 answer that we had heard was that they were very, 4 very -- they thought it was very unlikely that 5 they could enroll enough patients to make the 6 study valid. 7 Q Specifically what did 8 Doctor Beasley tell you about who he contacted, 9 when he contacted, and the results of his 10 contacts? 11 A Sir, I'm trying to be 12 very explicit with my testimony, and I don't 13 recall what Doctor Beasley told me specifically 14 about who he contacted or when he contacted or 15 what they said. 16 Q Specifically what did 17 Doctor D.J. Goldstein, MD, tell you concerning who 18 he contacted, when he contacted, and what the 19 results of those contacts were concerning finding 20 an investigator that had the facilities, time and 21 the patients to do such a study? 22 MR. FREEMAN: He's 23 already answered it several times that he doesn't 24 recall any of those conversations with any of 284 1 those people. 2 MR. SMITH: I'm going to 3 ask him individual by individual. 4 A I do not recall what 5 Doctor Goldstein told me specifically. 6 Q Do you recall speaking to 7 Doctor Goldstein specifically about this? 8 A Yes, sir, I do. 9 Q Specifically what do you 10 remember being said about that? 11 A I recall only in general 12 that both individually and collectively, in 13 meetings where we discussed our interest in 14 getting this study started as quickly as possible, 15 the uniform replies were that we had not been able 16 to find sufficient qualified investigators to 17 carry out the study, despite our very best intent 18 and a great deal of effort. 19 Q Specifically what did you 20 do in ascertaining who Doctor Heiligenstein had 21 talked to and what efforts he had made in finding 22 an investigator or enough patients to do the 23 study? 24 A I certainly talked with 285 1 Doctor Heiligenstein and asked him, and he was 2 certainly part of meetings in which we discussed 3 the problem of finding qualified investigators, 4 and as I've told you, the best I can recall is 5 that the uniform reply from all the people that 6 were responsible for this was that they could not 7 identify an adequate number of qualified 8 investigators in the United States or 9 internationally. 10 Q Did you call in some 11 outside consultants to help you with this? 12 A Yes, sir. 13 Q Who? 14 A I do not recall their 15 specific names. 16 Q You can't recall any 17 names as we sit here today on this important issue 18 that was going to prove that Prozac reduced 19 suicidality instead of causing it? 20 A I cannot recall the 21 specific names that you requested, which were of 22 the experts that were called in to address this 23 issue. 24 Q You can't recall the 286 1 specific names of any investigators that were 2 contacted either, can you, Doctor Thompson? 3 A No, sir, because you 4 asked me to be very correct in my testimony, and I 5 want to make sure that I am correct in that 6 testimony, and therefore I don't want to say 7 something that's wrong. 8 Q You can only speak in 9 generalities in this particular area, correct? 10 A And could you tell me 11 what the definition of -- 12 Q Generalities concerning 13 what efforts were made to secure the completion -- 14 the start and the completion of this protocol of 15 such a significant issue. 16 A I've testified to the 17 very best of my ability. 18 Q Which is only generality? 19 A That's your definition, 20 sir. 21 Q Well, you can't tell me 22 the names of any consultants who were contacted? 23 A I cannot tell you the 24 names of any consultants. 287 1 Q You can't tell me the 2 names of any investigators that were consulted? 3 A That's correct, sir. 4 Q And you can't tell me any 5 specific discussions you had with any of these 6 individuals listed on your staff or under your 7 direction who were responsible for securing 8 this -- 9 A That's how I've 10 testified. 11 Q -- about their efforts, 12 correct? 13 A Yes, sir. 14 Q Did you do anything 15 independently to secure a consultant or an 16 investigator or get this done, Doctor Thompson? 17 A Well, I certainly 18 participated in meetings and discussions of this, 19 but if by independently you mean did I call up a 20 potential investigator, no, I did not. 21 Q Why didn't you just take 22 the bull by the horns? You seem to not be shy in 23 attacking and undertaking a complicated problem. 24 A I guess I don't 288 1 understand the question, why didn't I take the 2 bull by the horns. I thought in fact I was taking 3 the bull by the horns. We had frequent meetings. 4 I'd assigned extremely competent world class 5 people to this task. They knew people directly 6 that I didn't know personally. They had access to 7 resources and identifying investigators that had 8 done studies for us and for others on a worldwide 9 basis. I put the very best resources we had to 10 this task. I would have not been the most 11 competent person to do this, and in fact it would 12 have been silly for me to use my time, rather than 13 the time of the real experts, to carry out this 14 very important task. 15 Q Did you talk with Doctor 16 Perelman? 17 A Yes, sir. 18 Q Or Doctor Herr -- 19 A Yes, sir. 20 Q -- about the problems 21 that were being encountered -- 22 A Absolutely. 23 Q -- in finding enough 24 patients and enough investigators? 289 1 A Yes, sir. 2 Q Did you ask their 3 assistance and help in this pressing problem? 4 A They were very supportive 5 in allowing us to make use of the resources to try 6 to get this going, because we were all three, as 7 well as many other people at Lilly, very, very 8 interested in having this study done because we 9 thought this would be a very definitive study for 10 the drug. 11 Q You see, one of the 12 reasons for my questioning you on this is, Doctor 13 Thompson, if you go back and look at Exhibit 1, 14 authored by you a year and two months earlier, 15 you're talking about pulling out the stops, about 16 the FDA being very skitterish, having twenty 17 full-times at least working on Prozac post- 18 marketing safety, and you say if necessary we will 19 stop everything else going on to provide more 20 support, you say every event -- significant event 21 about Prozac has been a show stopper with twelfth 22 floor meetings immediately with Earl, Mel, 23 et cetera, right? 24 A Yes, sir. 290 1 Q You say there can't be a 2 fumble of minor proportion, right? 3 A That's correct. 4 Q You say in Exhibit 2, 5 Lilly can go down the tubes if we lose Prozac, 6 don't you? 7 A Yes, sir. 8 Q And you're saying that 9 you're really going to be up in arms with Allen if 10 he doesn't -- or not with Allen, but with Patrick 11 Keohane if he doesn't get the proper attitude 12 about getting this problem solved, correct, or 13 getting this matter attended to? 14 A Well, it says if I hear 15 one more problem about not covering Prozac safety 16 in the UK, Allen, I'm going to really be up in 17 arms, that's what I said. 18 Q Did you feel less 19 strongly about the rechallenge protocol than you 20 did about the post marketing safety reports in the 21 United Kingdom? 22 A Oh, not at all. 23 Q Okay. Did you issue any 24 memos to any of your personnel similar to those 291 1 memos in Exhibit 1 and 2 saying we're going to 2 pull out any stops, we don't care what it takes, 3 we're going to get this job done? 4 A I certainly said that. 5 You haven't shown me any memos where I said that 6 in writing. 7 Q I haven't seen any memos 8 where you said that in writing. 9 A Well, I certainly said 10 that at meetings. 11 Q I haven't seen any memos 12 really saying that there was a problem getting 13 enough patients or enough investigators to 14 complete this study, Doctor Thompson? 15 A Well, there certainly -- 16 that was the critical issue, and it was consuming 17 a great deal of our effort, and we had done 18 everything that I knew to do using a large number 19 of world class experts at Lilly, not only in the 20 United States, but internationally. 21 Q But this was going to 22 solve the problem for you, wasn't it? 23 A I certainly thought so. 24 Q Go back to Exhibit 10. 292 1 A Yes, sir. 2 Q Point 2 there says that 3 Lilly has agreed to incorporate the modified scale 4 for suicidal ideation, revised, in ongoing and 5 planned US and UK clinical trials, correct? 6 A Yes, sir. 7 Q Was that done? 8 A I don't know whether it 9 was done explicitly or not. 10 Q Hadn't the FDA asked that 11 that be done? 12 A Well, again, we've talked 13 before about what asked means -- 14 Q Do you do what the FDA 15 asks or what they require or command, Doctor 16 Thompson? 17 A You interrupted my 18 answer. Which one would you like me to answer? 19 Q Go ahead and complete 20 your first answer before I interrupted you, and I 21 apologize for that. 22 A As I indicated before, 23 Lilly was very much interested in getting all of 24 the valid data that we could that addressed this 293 1 issue. The FDA shared that concern. We had a 2 number of conversations talking about how could we 3 get scientifically valid data to address this. If 4 you want to interpret that as saying that the FDA 5 asked us to do it, my interpretation would be that 6 they had agreed with us that we ought to do 7 everything that was scientifically valid, but not 8 anything that wasn't scientifically valid. And 9 the difficulty here, and the reason I want to make 10 very clear on this point, is the FDA any time, of 11 course, has the absolute right to command us to do 12 a study, and they can command the exact design and 13 when we will begin it and how we'll do it, and 14 they always have that authority. That never 15 happened. 16 So, in the sense of 17 asking, we were sitting around a table and we were 18 all saying it will really be helpful to have these 19 kinds of data, yes, we had agreement and alignment 20 with the FDA. They made suggestions, we made 21 suggestions. In the sense of asking and any 22 officer of the FDA telling me, or anyone else to 23 my knowledge at Lilly, this is something that we 24 expect you to do, I do not believe that that ever 294 1 happened. 2 Q See, they hadn't -- the 3 way you read this memo, they didn't have to 4 command that you do it because it appears on May 5 15th, 1991 that you've already agreed to do it, 6 correct? 7 A That's what Doctor 8 Kotsanos says. 9 Q Did you think he's wrong? 10 A Well, I don't think I was 11 at the meeting; I don't know, therefore, exactly 12 what the word agreed means. I can tell you that 13 we certainly had the intention of doing these 14 studies, but only if in fact they would be 15 scientifically valid, and we had written a 16 proposed protocol, as we have on many other 17 occasions, and found that in fact we could not 18 effect a scientifically valid study, and that's 19 why it wasn't done. 20 Q I didn't think there was 21 any problem with the scientific validity of the 22 protocol that was being presented to the FDA; I 23 thought the problem was in finding enough 24 investigators with enough patients to actually do 295 1 it? 2 A You are correct, but 3 scientific validity would include having a result 4 that scientists could analyze and agree to the 5 data. If we had implemented that protocol and 6 only enrolled twenty or thirty or forty patients, 7 we wouldn't have enough data that anyone would 8 have found a scientifically valid analysis. 9 Q How many patients did the 10 protocol call for? 11 A Two hundred. 12 Q All right. Again, the 13 protocol wasn't even begun? 14 A That's correct. 15 Q Could you have enrolled 16 twenty, thirty, forty patients in a pilot study, 17 Doctor Thompson, to give you some further insights 18 into this issue? 19 A Well, that was exactly 20 what the plan was, to put enough investigators at 21 work so that after six months we could make an 22 assessment of how the protocol was going; but we 23 in fact couldn't find enough investigators who 24 thought they could enroll enough patients that 296 1 they would spend their time doing it, because 2 if -- do you want me to complete it? 3 Q Yes. 4 A If an investigator worked 5 real hard on doing this protocol, but was only 6 able to enroll one or two patients, and therefore 7 couldn't analyze the data nor contribute to an 8 overall pooled analysis, they would have wasted 9 their time. 10 Q Well, but if you got 11 twenty or forty patients, you would at least have 12 enough patients for a pilot study, wouldn't you? 13 A Well, all that would have 14 probably told you is whether or not you could 15 enroll at that rate. I mean, whether the protocol 16 was doable in the sense that patients would 17 agree -- you could find patients to meet the 18 criteria and they would agree in fact to being 19 treated under the protocol, and you could get them 20 to complete the protocol and in fact the data 21 could be collected, but you couldn't draw a 22 conclusion from that that would have any meaning. 23 Q But you would have a 24 pilot study, wouldn't you? 297 1 A If you want to call it a 2 pilot study. 3 Q Lilly does pilot studies, 4 don't they? 5 A Not very often. 6 Q They did pilot studies in 7 connection with Prozac, didn't they? 8 A We have done some pilot 9 studies, but we try to avoid them whenever 10 possible. 11 Q I mean, you did pilot 12 studies in connection with Prozac, didn't you? 13 A We have done pilot 14 studies, but we try to avoid them. 15 Q On Prozac? 16 A I said we have done pilot 17 studies on Prozac, but we try to avoid them 18 because it takes a great deal of time and effort 19 if in fact those studies will not continue to a 20 scientifically valid conclusion. 21 Q No pilot study -- no 22 pilot rechallenge study was done, was it? 23 A I do not believe so. 24 Q No rechallenge study was 298 1 done? 2 A I think that's correct. 3 Q No prospective study was 4 done? 5 A That is wrong. 6 Q Specifically look at -- 7 specifically designed to look at suicidal 8 ideation? 9 A Well, remember, I think 10 I've testified today repeatedly on the fact that 11 there is a very high level of scientific validity 12 in the very well controlled studies that we did 13 using a very comprehensive data collection method 14 for all safety events, and -- 15 Q Then why did you agree to 16 do a rechallenge study if you thought your data 17 was sufficient to start with? 18 A Would you like me to 19 complete the former answer or answer the new 20 question? 21 Q I'm sorry, I thought you 22 had. Complete your answer. 23 A I was saying that there 24 was a high level of scientific validity in the 299 1 prospective studies that were being done using 2 either the Hamilton depression scale or the Marie 3 Asberg scale with the intense and highly 4 comprehensive way in which we collect safety data. 5 Q Was there ever, as agreed 6 in March of 1991, a modified scale for suicidal 7 ideation incorporated into ongoing and planned US 8 and UK trials? 9 A I don't know that. I 10 know that we were trying to develop a modified 11 scale, but I'm not sure whether we ever had, in 12 fact, a validated modified scale. 13 Q Was there ever a 14 descriptive study of patients reported to develop 15 intense violent suicidal thoughts? 16 A Well, study is, again, a 17 difficult word. I'm sorry, as a scientist, I'm 18 not trying to be pedantic, but in fact the 19 enormous amount of data that Lilly was collecting 20 in a worldwide effort to look at all safety 21 adverse events was in fact an extremely large and 22 very well done epidemiological study. 23 Q In your opinion? 24 A Yes, sir, as chief 300 1 scientific officer of Eli Lilly and Company. 2 Q I'm just -- yes, it's 3 your opinion as the chief scientific officer of 4 Eli Lilly and Company? 5 A Yes, sir. 6 Q Your employer currently? 7 A Yes, sir. 8 Q And then? 9 A Yes, sir. 10 Q The word study was not 11 used by me, it's used by your colleague, Doctor 12 Kotsanos. 13 A Yes, sir. 14 Q In Point 4. 15 A Yes, sir. 16 Q So do you know what he 17 means when he stays study, Doctor Thompson? 18 A Yes, sir, that we would 19 attempt to collect all of the reports that we 20 could that described the development of intensive 21 violent suicidal thoughts, and in fact we did 22 that. If you read further, of course, you will 23 note that the FDA in fact questioned how useful 24 these data would be, so there was a scientific 301 1 debate, whoever Doctor Stadel is thought that it 2 was worth pursuing, but in fact we carried that 3 out in the sense that we did the most 4 comprehensive search we could to gather all the 5 data from all of the lay reports, scientific 6 reports, verbal reports, everything every Lilly 7 employee, all thirty thousand of us, heard around 8 the world that addressed this issue. That's an 9 extraordinary -- an extraordinary epidemiological 10 study. I'm not sure anyone has ever done one of 11 that comprehensive nature, considering the fact 12 that at this time we think that perhaps ten 13 million people have taken this drug around the 14 world or more, and that's an extraordinary study. 15 Q Anything else you want to 16 add to that, Doctor Thompson, any other company 17 lines you want to proclaim? You may as well get 18 it all out. 19 A No, speaking as the chief 20 scientific officer -- 21 MR. BRENNAN: I object to 22 the side bar by plaintiffs' counsel. 23 MS. ZETTLER: That was a 24 question. 302 1 MR. BRENNAN: That was 2 not a question, that was an editorial comment 3 about which you -- 4 MS. ZETTLER: How many 5 lawyers are going to represent this witness 6 today? 7 MR. FREEMAN: About four 8 or five. 9 MS. ZETTLER: Five, okay, 10 as long we know that. 11 Q (BY MR. SMITH) The issue 12 of a ten milligram dose came up at this meeting 13 apparently, according to Doctor Kotsanos? 14 A Yes, sir. 15 Q Had that issue ever come 16 up with the Food and Drug Administration prior to 17 May 15th, 1991? 18 A I don't remember if it 19 was before or whether this was the first time that 20 they had asked about that. We were very much 21 interested, in fact, at developing that dose, and 22 I don't remember time course of those discussions. 23 (THOMPSON EXHIBIT NO. 11 MARKED FOR 24 IDENTIFICATION.) 303 1 Q Exhibit 11 is a document 2 authored by you dated November 5th, 1990, is it 3 not? 4 A Yes, sir. 5 Q Do you recall authoring 6 this document? 7 A Yes, sir, I do. 8 Q Is this a document that 9 you reviewed in preparation for your deposition, 10 Doctor Thompson? 11 A No, sir -- well, I'm not 12 sure. 13 Q When do you last 14 specifically have a recollection of seeing this 15 document? 16 A I don't remember whether 17 it was one of the ones we reviewed in the last 18 month or whether I haven't seen it since 1990. 19 Q It looks to me like 20 you've got some pretty definite ideas set forth in 21 this document concerning how to get investigators 22 and how to conduct clinical trials and how to 23 probably do FDA mandated studies with fluoxetine 24 looking at suicidality, doesn't it? 304 1 A Well, I'm asking for 2 advice from my colleagues because, if you recall, 3 I ended this saying, "Complex, yes. Any simpler 4 ideas?" This was, in fact, a major logistical 5 problem for us and I was proposing one potential 6 solution. 7 Q You say in preparation 8 for PSC, what's that? 9 A Pharmaceutical Strategy 10 Committee. 11 Q Various groups -- you're 12 a member of that committee, were you not? 13 A Yes, sir. 14 Q Various groups have been 15 talking about our ability to manage antidepressant 16 clinical trials worldwide. We need to be able to 17 study five antidepressants that are new including 18 blank, and probably do the FDA mandated study with 19 fluoxetine looking at suicidality, right? 20 A Yes, sir. 21 Q You say this will require 22 a very, very large number of psychiatrists and 23 patients in every country possible. Assuming we 24 all agree on that, then the question is how to 305 1 organize them. Should they all work on one 2 protocol design? Should they all work on a single 3 compound until it is done and then roll over to a 4 second? What are our priorities? Correct? 5 A Yes, sir. 6 Q You go on to say I 7 suggest our priorities are, one, protect Prozac. 8 Correct? 9 A Yes, sir. 10 Q Two, get something 11 registered for depression. Correct? 12 A Yes, sir. 13 Q And three, get any other 14 compound registered for depression. Correct? 15 A Yes, sir. 16 Q Four, get blank or others 17 registered for any nondepression indication. 18 A Yes, sir. 19 Q You say I suggest not 20 using only one protocol for several reasons. We 21 have no idea which design will work. We don't 22 want to have a hundred investigators in one 23 protocol if it fails. Right? 24 A Yes, sir. 306 1 Q Then you go on to suggest 2 why not try to count some of the patients in our 3 new compounds -- on our new compounds in the ten 4 thousand patients FDA wants us to use in studying 5 suicidality? How? 6 A Yes, sir. 7 Q Simple, include 8 fluoxetine twenty milligram QD as one arm in each 9 of the new studies and include all the metrics we 10 need for suicidality. Correct? 11 A Yes, sir. 12 Q Was that done? 13 A It is my belief that in 14 fact fluoxetine was used as a comparator in some 15 of those studies. 16 Q When did the FDA request 17 that you include ten thousand patients in studying 18 suicidality? 19 A In having meetings with 20 the FDA addressing this issue, that was the 21 general accepted number we were talking about of 22 patients that would have to be studied in order to 23 have enough patients with the emergence of 24 suicidality to make conclusions about -- among the 307 1 various forms of treatment to be studied. 2 Q Did you agree with that? 3 A Yes, sir. 4 Q That it would take that 5 many patients? 6 A Yes, sir. 7 Q Would that be patients on 8 Prozac or would that be patients including 9 comparators and placebo? 10 A Ten thousand was assuming 11 that some of those patients would be on Prozac and 12 some would be on placebo and some would be on 13 comparators. 14 Q All right. Why was a 15 protocol then submitted for a rechallenge study 16 only studying two hundred patients? 17 A They were entirely 18 different kinds of studies. This would have been 19 looking at patients who were being studied for 20 depression, not necessarily those who had had any 21 evidence of suicidality in the past. And the 22 incidence of the emergence -- in a normal five- or 23 six-week efficacy safety study of antidepressants, 24 the incidence of suicidality emerging was so low 308 1 that we thought it would take about that size 2 study to show any significant difference among 3 Prozac, placebo and comparators. 4 Q Doctor Thompson, how many 5 patients completed the Prozac clinical trials that 6 were deemed to be pivotal by Lilly and the FDA? 7 A I don't really remember 8 which ones were deemed pivotal. If you're talking 9 about -- I think it was Protocol -- was it 27 that 10 had, I think, six investigators, is that right? I 11 don't recall -- I recall the total number of 12 patients that were in the NDA that we submitted 13 was just over two thousand, and my guess is that 14 there were five hundred patients in those -- in 15 Protocol 27, but that's just a guess. 16 Q So you think there were 17 two thousand patients in the clinical trials 18 submitted as part of the NDA? 19 A I think in the initial 20 NDA submission, which as you said was in September 21 of -- 22 Q But now the FDA, or at 23 least in 1990, the FDA was requiring that you look 24 at ten thousand patients, five times as many 309 1 patients as it examined in the clinical trials to 2 examine the issue of suicidality, is that correct? 3 A Yes. Would you like me 4 to complete the previous answer or -- 5 Q I'd just like for you -- 6 I thought you had completed the answer. 7 MR. FREEMAN: Go ahead 8 and complete it. 9 A Well, I was trying to be 10 explicit about the answer so I was absolutely 11 correct. I think in the NDA submitted -- the 12 initial NDA of Prozac submitted in the United 13 States in September of 1983, that the total number 14 of patients in the trials, not all of whom 15 received Prozac, was just over two thousand. 16 Q All right. 17 A Your next question then 18 was, the FDA and we were now talking about the 19 need to study as many as ten thousand patients. 20 Q Yes. 21 A The purpose of those 22 clinical trials were, however, quite different. 23 The first set in the New Drug Application was 24 specifically to establish the safety and efficacy 310 1 of fluoxetine for the treatment of major 2 depression. The reason for the need of ten 3 thousand patients was to address another issue, 4 which was would the emergence of suicidality occur 5 more frequently, less frequently, or with the same 6 frequency when the patient was treated with 7 fluoxetine as opposed to a placebo or an 8 alternative active antidepressant. 9 Q Were placebos and 10 alternative antidepressants used in the clinical 11 trials -- 12 A Yes, sir. 13 Q -- Doctor Thompson? 14 A Yes, sir. 15 Q Was this ten-thousand- 16 patient study ever done? 17 A No, sir. Well, let me 18 back up on that one just a moment and give you two 19 qualifiers. First of all, there was not a single 20 study of ten thousand, and what I was proposing 21 here was that in fact we get to that number by 22 carefully designing studies of -- if you recall, 23 up to five new antidepressants, et cetera. In 24 fact, the total database on trials of fluoxetine 311 1 and other drugs with similar activity I think 2 actually now is bigger than ten thousand. But in 3 terms of whether these specific ten thousand 4 testing in depressed patients new antidepressants 5 was done, no, we haven't gotten to that number 6 yet. 7 Q Has protecting Prozac 8 always been your number one priority in designing 9 clinical trials, in hiring psychiatrists, and in 10 selecting patients? 11 A No, sir. 12 Q Why did you have 13 protecting protocol -- protecting Prozac as your 14 priority in connection with securing this ten- 15 thousand-patient trial that the FDA was interested 16 in? 17 A Well, I don't think this 18 memo addresses in any way hiring psychiatrists. 19 What this -- 20 Q Beg your pardon? 21 A I don't think this memo 22 addresses hiring psychiatrists in any way. I 23 think what the memo suggests -- addresses 24 specifically is that we had a great number of new 312 1 compounds that we thought would work in 2 depression. We needed to design studies to 3 establish their safety and efficacy. In designing 4 those studies, it would be possible to get 5 scientifically valid and relevant data to address 6 the issue of Prozac suicidality, if in fact we had 7 designed them with that goal in mind. And 8 overall, at that time, in terms of designing new 9 studies of Prozac and other antidepressants, I 10 said my -- I suggested the priorities were first 11 to protect Prozac. You see, one would probably 12 not have ordinarily said to include Prozac as a 13 comparator in a trial of New Drug X, so that if 14 one were to do that, you would have to have 15 another reason. If you just wanted to prove that 16 Drug X worked compared to placebo and imipramine, 17 you wouldn't necessarily include Prozac. And so I 18 was saying I'm suggesting that that's the number 19 one priority, and that would lead to a change in 20 the design that we would normally follow with new 21 antidepressants. 22 Q Why did you want to 23 protect Prozac? 24 A Because Prozac was under 313 1 attack in an extraordinary fashion with people 2 asserting that in fact there was something wrong 3 with it, especially related to the issue of 4 violence and murder and suicidality. 5 MR. FREEMAN: It's about 6 5:00 o'clock, let's sort of wind up and go in 7 seven hours. 8 Q (BY MR. SMITH) You 9 indicate in Exhibit 11 that we need to be able to 10 study five antidepressants that are including -- 11 that are new, including blank, and probably do the 12 FDA mandated study with fluoxetine looking at 13 suicidality, correct? 14 A Yes, sir. 15 Q Now, earlier you had said 16 that the FDA never required that you do any 17 particular study. 18 A That's correct. 19 Q Now in this document, 20 you're saying that there is an FDA mandated study, 21 are you not? 22 A I misspoke. I said that 23 in this document, but in fact I was correct in 24 testifying that the FDA never required that a 314 1 study of that type be done. 2 Q Do you know of any other 3 instance where you misspoke, Doctor Thompson? 4 A Not in my testimony or in 5 the documents you've shown me so far. 6 Q Have you seen any 7 documents, in your review of the documents in 8 preparation for your deposition, where you 9 misspoke? 10 A I can't remember any 11 now. 12 MR. FREEMAN: 9:00 13 o'clock? 14 MR. SMITH: That would be 15 fine with me. 16 (DEPOSITION ADJOURNED.) 17 * * * * * 18 19 20 21 22 23 24 315