1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT DIVISION ONE (1) 2 3 JOYCE FENTRESS, ET AL. PLAINTIFFS 4 5 VS. DEPOSITION FOR PLAINTIFFS 6 7 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 8 * * * * * * * * * * 9 10 DEPONENT: DR. CHARLES BEASLEY 11 DATE: MAY 17 AND 18, 1994 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 20 (502) 589-2273 Page 1 1 * * * * * * * * * * 2 3 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 4 INDIANAPOLIS DIVISION 5 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 6 Litigation ) 7 * * * * * * * * * * 8 NO. 91-02496-A 9 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 10 V. ) DALLAS COUNTY, TEXAS ) 11 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 12 * * * * * * * * * * 13 NO. 92-14775-E 14 RICHARD HAROLD CROSSETT, JR., ) IN THE 15 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT, ) COURT OF 16 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 17 JOCQUETTA ANN CROSSETT, DECEASED ) ) 18 V. ) DALLAS COUNTY, ) TEXAS 19 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 20 PSYCHIATRIC COMPANY, INC. ) D/B/A/ HCA WILLOW PARK ) 101ST JUDICIAL 21 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D. ) Page 2 1 * * * * * * * * * * 2 NO. A-921,405-C 3 MARIA GUADALUPE REVES ) IN THE 4 INDIVIDUALLY AND AS NEXT ) DISTRICT COURT FRIEND OF GRANT JULIAN REVES ) OF 5 A MINOR CHILD, AND ON BEHALF ) OF THE ESTATE OF CHRISTIAN ) 6 MARIE REVES, DECEASED ) ) ORANGE COUNTY, 7 V. ) TEXAS ) 8 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, RAVIKUMAR ) 9 KANNEGANTI, M.D., HOSPITAL ) CORPORATION OF AMERICA, A ) 10 TENNESSEE CORPORATION, HEALTH ) SERVICES ACQUISITION CORP., ) 11 A DELAWARE CORPORATION, ) HCA PSYCHIATRIC COMPANY, A ) 12 DELAWARE CORPORATION, TEXAS ) PSYCHIATRIC CO., INC.. A/K/A ) 13 AND/OR D/B/A HCA BEAUMONT ) NEUROLOGICAL HOSPITAL, AND HCA ) 14 HEALTH SERVICES OF TEXAS, INC. ) 128TH JUDICIAL A/K/A AND/OR BEAUMONT ) DISTRICT 15 NEUROLOGICAL HOSPITAL ) Page 3 1 * * * * * * * * * * 2 3 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS COUNTY DEPARTMENT - LAW DIVISION 4 RENATO DI SILVESTRO, Individually ) 5 and as Special Administrator of ) the Estate of JOHN DI SILVESTRO, ) 6 Deceased, ) ) 7 Plaintiff, ) ) 8 v. ) No. 91 L 7881 ) 9 ROBERT L. NELSON, et al., ) ) 10 Defendants, ) ) 11 GEORGE MELNICK, M.D. and PETER ) FINK, M.D. ) 12 ) Respondents in Discovery.) 13 * * * * * * * * * * Page 4 1 2 SUPERIOR COURT OF THE STATE OF CALIFORNIA 3 FOR THE COUNTY OF LOS ANGELES 4 DR. MARIUS SAINES, etc., et al., ) Case No: ) SC 008331 5 Plaintiffs, ) ) 6 vs. ) ) 7 ELI LILLY & COMPANY, a corporation; ) DISTA PRODUCTS COMPANY, a division ) 8 of Eli Lilly & Company; and DOBS 1- ) 100, inclusive, ) 9 ) Defendants. ) 10 ____________________________________) 11 * * * * * * * * * * 12 NO. 93-8792-D 13 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT 14 ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF INDIVIDUALLY AND AS SURVIVORS ) 15 AND STATUTORY BENEFICIARIES ) OF MAY YUN KUNG, DECEASED ) 16 ) VS. ) DALLAS, COUNTY 17 ) T E X A S ELI LILLY AND COMPANY, DISTA ) 18 PRODUCTS COMPANY, AND MONIQUE ) KUNKLE, PH.D. ) Page 5 1 * * * * * * * * * * 2 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS 3 CIVIL COURT DEPARTMENT 4 EUGENE HUSLIG, AS ADMINISTRATOR ) 5 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 6 HUSLIG, DECEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 7 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 8 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 9 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 10 ) 94 C 192 PLAINTIFFS, ) 11 VS. ) COURT NO. 7 ) CHAPTER 60 12 MARY L. BILLINGSLEY, EXECUTOR OF ) THE ESTATE OF THAD BILLINGSLEY, ) 13 M.D., DECEASED D/B/A THE BENESSERE ) CENTER, SUSAN C. JOHNSON, PH.D., ) 14 BILLINGSLEY ENTERPRISES, INC., ) F/K/A THAD H. BILLINGSLEY, M.D. ) 15 CHARTERED, D/B/A THE BENESSERE ) CENTER, ELI LILLY AND COMPANY, ) 16 AND DISTA PRODUCTS COMPANY, ) ) 17 DEFENDANTS. ) 18 * * * * * * * * * * Page 6 1 * * * * * * * * * * 2 CAUSE NO. 93-04911-A 3 LINDA JILL WELCH, CARLINDA 4 WELCH REX, CONNAN ROSS WELCH AND CHAD MICHAEL WELCH, 5 INDIVIDUALLY AND AS SURVIVORS AND STATUTORY BENEFICIARIES 6 OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 7 V. 8 ELI LILLY AND COMPANY, DISTA PRODUCTS COMPANY, NOE NEAVES, 9 M.D., AND MINITH-MEIER CLINIC, P.A. DEFENDANTS Page 7 1 THE DEPOSITION OF DR. CHARLES BEASLEY TAKEN 2 AT THE OFFICE OF BAKER & DANIELS, 300 NORTH 3 MERIDIAN STREET, SUITE 2700, INDIANAPOLIS, 4 INDIANA 46204, ON MAY 17 AND 18, 1994; SAID 5 DEPOSITION TAKEN PURSUANT TO NOTICE IN ACCORDANCE 6 WITH THE RULES OF CIVIL PROCEDURE. 7 * * * * * * * * * * 8 A P P E A R A N C E S 9 10 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 11 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 12 PAUL SMITH 13 COUNSEL FOR PLAINTIFFS 745 CAMPBELL CENTER 2 14 8115 NORTH CENTRAL EXPRESSWAY DALLAS, TEXAS 75206 15 LAWRENCE J. MYERS 16 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 17 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 18 ATLANTA, GEORGIA 30308-3243 19 MARGARET M. HUFF ELI LILLY AND COMPANY 20 LILLY CORPORATE CENTER INDIANAPOLIS, INDIANA 46285 Page 8 1 BEATRICE M. SMITH COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 2 FRIEND & ASSOCIATES LLP 1301 MCKINNEY #2900 3 HOUSTON, TEXAS 77010 4 BARTON BROWN COUNSEL FOR DR. BILLINGSLEY 5 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 10111 W. 87TH ST. 6 P.O. BOX 12290 OVERLAND PARK, KANSAS 66282 7 ROBERT L. HARRIS 8 COUNSEL FOR NOE NEAVES, M.D. SIFFOLD & ANDERSON, LLP 9 6300 NATIONS BANK PLAZA 901 MAIN STREET 10 DALLAS, TEXAS 75202 11 WILLIAM J. DOWNEY, III COUNSEL FOR PLAINTIFF SAINES 12 KANANACK, MURGATROYD, BAUM & HEDLUND 12100 WILSHIRE BOULEVARD, SUITE 650 13 LOS ANGELES, CALIFORNIA 90025 14 KATHERINE L. LAWS COUNSEL FOR DRS. WITSCHY AND KANNEGANTI 15 BAILEY & WILLIAMS 3500 NCNB PLAZA 16 901 MAIN STREET DALLAS, TEXAS 75202-3714 Page 9 1 I N D E X 2 3 DEPOSITION OF DR. CHARLES BEASLEY 4 5 DIRECT EXAMINATION BY MR. SMITH 12 6 FURTHER EXAMINATION BY MR. SMITH 273 7 CROSS EXAMINATION BY MS. ZETTLER 376 8 REDIRECT EXAMINATION BY MR. SMITH 507 9 10 CERTIFICATE 509 11 ERRATA 510 12 EXHIBITS 13 PLAINTIFFS' EXHIBIT NO. 1 143 PLAINTIFFS' EXHIBIT NO. 2 167 14 PLAINTIFFS' EXHIBIT NO. 3 200 PLAINTIFFS' EXHIBIT NO. 4 208 15 PLAINTIFFS' EXHIBIT NO. 5 212 PLAINTIFFS' EXHIBIT NO. 6 217 16 PLAINTIFFS' EXHIBIT NO. 7 280 PLAINTIFFS' EXHIBIT NO. 8 298 17 PLAINTIFFS' EXHIBITS NO. 9 AND 10 317 PLAINTIFFS' EXHIBIT NO. 11 354 18 PLAINTIFFS' EXHIBIT NO. 12 388 PLAINTIFFS' EXHIBIT NO. 13 394 19 PLAINTIFFS' EXHIBIT NO. 14 411 PLAINTIFFS' EXHIBIT NO. 15 412 Page 10 1 COMES CHARLES BEASLEY, M.D., CALLED BY 2 THE PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, 3 WAS DEPOSED AND TESTIFIED AS FOLLOWS: 4 * * * * * * * * * * 5 MR. MYERS: Paul, do we have the same 6 agreement with respect to your various state 7 court cases? 8 MR. SMITH: Not unless you rattle them 9 off. 10 MR. MYERS: Biffle, Welch, Crossett, 11 Reves, Kung, and the Huslig case in Kansas. 12 MR. SMITH: How about the Houston 13 cases? 14 MR. MYERS: You didn't issue a notice 15 for those, but if you want to use it under the 16 same circumstances, that's fine with respect to 17 the MDL order. 18 MS. ZETTLER: Same with my Illinois 19 cases: 20 MR. HARRIS: Do you want Welch in that 21 group? 22 MR. MYERS: Yes. 23 MS. LAWS: And all the other 24 objections are still in place. Page 11 1 MS. ZETTLER: What would we do without 2 you. 3 MS. LAWS: You would probably have all 4 these depositions that are ambiguous with respect 5 to what the rules will be. 6 * * * * * * * * * * 7 DIRECT EXAMINATION 8 BY MR. SMITH: 9 Q. Would you state your name, 10 please. 11 A. Charles Merritt Beasley, 12 Junior. 13 Q. Merit? 14 A. Merritt. 15 Q. Like in merit pay raise? 16 A. M-E-R-R-I-T-T. 17 Q. How old a man are you, Doctor 18 Beasley? 19 A. I'm forty-four. 20 Q. And where do you live? 21 A. I live at XXXXXXXXXXXXXXXXXX 22 XXXXXXXXXXXXXXXXXXXXXXXXX. 23 Q. Are you a married man? 24 A. Yes, I am. Page 12 1 Q. Does your wife work outside 2 the home? 3 A. Yes, she does. 4 Q. Is she an employee of Eli 5 Lilly and Company? 6 A. No, she's not. 7 Q. Children? 8 A. No. 9 Q. Are you a medical doctor? 10 A. Yes, I am a medical doctor. 11 Q. Would you give for us, please, 12 your educational background starting with when 13 and where you graduated from high school? 14 A. Yes. I graduated from high 15 school in Lexington, Kentucky in 1968. I 16 received my B.A. degree from Yale in 1977. I 17 completed my medical education at the University 18 of Kentucky, 1983. I did one year of psychiatric 19 residency at Yale in '83, '84, and did my 20 psychiatric residency at the University of 21 Cincinnati in 1987, was Board certified in 22 general adult psychiatry in 1988, and I have been 23 working for Eli Lilly and Company since July of 24 1987 when I completed the residency. Page 13 1 Q. I missed where you did your 2 one-year of psychiatric residency? 3 A. Yes, that was at Yale. 4 Q. Then after you completed that, 5 I would assume in 1984? 6 A. That's correct. 7 Q. You went to the University of 8 Cincinnati? 9 A. That's correct. 10 Q. And did what, a fellowship? 11 A. No, that was the completion of 12 the general psychiatric residency. 13 Q. And you completed that in? 14 A. In 1987. 15 Q. And came to work directly for 16 Eli Lilly and Company after you completed your 17 residency? 18 A. That's correct. 19 Q. Then you had never been 20 engaged in the private practice of psychiatry at 21 all after you finished your training? 22 A. After I finished my training, 23 no, sir. 24 Q. All of the clinical practice Page 14 1 of psychiatry that you ever engaged in, then, 2 would have been that clinical practice that you 3 participated in during your psychiatric residency 4 training? 5 A. Not quite correct in that I 6 did some work in a part-time position outside the 7 residency during my fourth year. 8 Q. Tell me about that. 9 A. There was a multi-specialty 10 group in Cincinnati, Group Health Associates, for 11 which I did some part-time work over probably the 12 two months prior to my completion of the 13 residency. 14 Q. Was that psychotherapy or was 15 that seeing patients in a hospital? 16 A. That was seeing patients in 17 this multi-specialty clinic on an out-patient 18 basis. 19 Q. Before you came to Eli Lilly 20 as a full-time employee, had you ever done any 21 work in any clinical trials, engaged in clinical 22 trials of psychotropic medications? 23 A. Yes, in fact I had. During my 24 residency, I worked part-time within an affective Page 15 1 disorders treatment clinic research program at 2 the University of Cincinnati headed by a faculty 3 member, Doctor Jack Hershowitz. I participated 4 in one clinical trial with an antidepressant. I 5 also served in a capacity, basically consultant, 6 to another clinical trial in the treatment of 7 bulimia that was conducted at the University of 8 Cincinnati as well. 9 Q. So as I understand it, you 10 were in some way participating in two clinical 11 trials? 12 A. That's correct. 13 Q. One had to do with affective 14 disorders, and it was an antidepressant trial, is 15 that right? 16 A. That's correct. 17 Q. And was that antidepressant 18 later marketed? 19 A. I believe it's marketed in 20 Europe, it's not marketed in the United States. 21 Q. What is the name of the 22 antidepressant? 23 A. I don't recall the name of the 24 antidepressant, it's a complex dopamine uptake Page 16 1 inhibitor. 2 Q. Is it a specific dopamine 3 uptake inhibitor? 4 A. As I recall, it had a number 5 of properties, but that was its primary activity. 6 Q. That depression trial, was 7 that for treatment of depressed individuals at 8 the affective disorder clinic? 9 A. That's correct. 10 Q. And did that antidepressant 11 trial use clinical -- 12 A. Excuse me, I do recall the 13 name, miniprin is the name of the compound. 14 Q. Spell that. 15 A. I believe it's 16 M-I-N-I-P-R-I-N, but I could be wrong about the 17 spelling. 18 Q. By whom is that drug 19 manufactured? 20 A. At the time, the U.S. sponsor 21 was Wyeth. 22 Q. Did you do clinical report 23 forms in connection with that trial? 24 A. Yes. Page 17 1 Q. And did you use treatment 2 measures or scales in rating the improvement or 3 lack of improvement of those individuals 4 participating in that trial? 5 A. Yes. 6 Q. What scales did you use? For 7 instance we've taken several depositions, several 8 dozen depositions in this case, and we're 9 familiar with, for instance, the HAM-D depression 10 scale used in the Prozac trial. Did you use any 11 scales similar to that? 12 A. Yes, I did. 13 Q. Which scales were used in 14 that? 15 A. We used the Ham-D, Hamilton 16 Depression Scale, the -- and the 17 Montgomery-Asberg depression rating scale. We 18 also used the CGI, Clinical Global impression 19 Scale. 20 Q. Any other scales? 21 A. None that I recall. 22 Q. The Montgomery-Asberg 23 Depression Scale, was that used in the Prozac 24 clinical trials? Page 18 1 A. I believe that it has been 2 used in some more recent trials. 3 Q. And does that scale have a 4 scale similar to the Ham-D-3, Ham-D item 3 5 suicidality assessment? 6 A. It has, I believe, the 7 equivalent item, item ten. 8 Q. Is it just one item on that -- 9 A. That's correct. 10 Q. -- scale? 11 A. That's correct. 12 Q. Is that the only item on that 13 scale that measured suicidality in any respect? 14 A. On the Montgomery scale, yes. 15 Q. How many subparts are there to 16 that item ten? 17 A. I believe there are six 18 ordinal points on that scale. 19 Q. You call them ordinal points? 20 A. That's correct. 21 Q. Now, the bulimia trial, was 22 that of an antidepressant drug or some other 23 psychotropic medication? 24 A. There were, I believe, two Page 19 1 active compounds involved, one was Imiprimine as 2 a reference control, one was Alprazolam. 3 Q. Give me that again? 4 A. Alprazolam, Xanax. There may 5 have been a placebo in that as well, I'm 6 uncertain. 7 Q. Has that trial been completed? 8 A. I believe it has, yes. 9 Q. Did it demonstrate any -- was 10 that for Xanax? 11 A. I believe it was. 12 Q. Who manufactures Xanax? 13 A. That would be UpJohn. 14 Q. And was UpJohn the sponsor of 15 that trial? 16 A. I believe they were. 17 Q. And did they determine the 18 efficacy of Xanax in treatment of bulimia in that 19 trial? 20 A. Given the nature of my 21 participation in that trial, I'm uncertain of the 22 outcome of that trial. 23 Q. All right. Because you just 24 had a -- you were exposed to that for just a Page 20 1 short period of time? 2 A. I had a very limited activity. 3 My task was to conduct or administer one 4 neuroendocrine challenge test that was being 5 included as part of the trial. 6 Q. In your training and 7 internship in psychiatry, were you involved in 8 that for a long enough period of time to develop 9 a special interest or special subspecialty within 10 psychiatry? 11 A. I clearly developed a special 12 interest in biological psychiatry and psychiatric 13 research. There's no recognized board of such at 14 this time for psychopharmacology or 15 psychopharmacology research. 16 Q. But psychopharmacology was 17 your primary interest? 18 A. Was my primary interest, yes. 19 Q. Is that why you went with 20 Lilly directly from school? 21 A. Yes. 22 Q. And from your post-graduate 23 training? 24 A. Correct. Page 21 1 Q. Did you apply with any other 2 pharmaceutical firms? 3 A. No. 4 Q. Why did you select Lilly? 5 A. The opportunity was made 6 available to me, it looked like a good 7 opportunity, and I decided to join them. 8 Q. Close to where you were raised 9 in Lexington, Kentucky? 10 A. That's correct. 11 Q. Closer than New Haven? 12 A. Closer than New Haven. 13 Q. What was your first job with 14 Lilly? 15 A. I was initially going to be 16 assigned to work in the analgesic development 17 program, but very soon after I was hired by 18 Lilly, they hired an additional person who was 19 assigned to that job, and I became more involved 20 with Fluoxetine. 21 Q. In what capacity, what was 22 your first job title? 23 A. My first job title was 24 associate clinical research physician. Page 22 1 Q. And for what years did you 2 hold that title? 3 A. I would have held that title 4 for two years. 5 Q. From July '87 to 1989 6 sometime? 7 A. That's correct. 8 Q. And was your work during that 9 time exclusively work on Fluoxetine, Prozac? 10 A. No, it wasn't, I was working 11 on an additional compound in development. 12 Q. What percentage of your time 13 was devoted to Fluoxetine, Prozac work during 14 that initial two years when you were an associate 15 clinical research physician? 16 A. I would say it was 17 approximately sixty to seventy percent. 18 Q. Was that other medication or 19 compound that you were working on at that time 20 later marketed by Lilly? 21 A. It has not been. 22 Q. All right. Was that other 23 compound a specific seratonin reuptake inhibitor? 24 A. No, it was not. Page 23 1 Q. Was that other compound an 2 antidepressant? 3 A. Yes, it was. 4 Q. What was the mode of action of 5 that other antidepressant? 6 A. It was a specific 7 norepinephrine uptake inhibitor. 8 Q. Is that product still under 9 investigation by Lilly? 10 A. Yes, it is. 11 Q. And has an IND or NDA been 12 submitted on that product? 13 A. An IND would have been 14 submitted to conduct research, an NDA has not 15 been submitted. 16 Q. All right. What was your next 17 job title with Lilly? 18 A. Clinical research physician. 19 Q. And for what time, what years 20 did you occupy that position? 21 A. I would have held that title 22 until March, 1992. 23 Q. During the two-year period of 24 time that you were an associate clinical research Page 24 1 physician, who was your immediate supervisor. 2 A. Dan Masica became my immediate 3 supervisor for the majority of that period, Mike 4 Draper was prior to that my supervisor. 5 Q. What was Dan Masica's job 6 title when he was your supervisor? 7 A. He was director of the 8 clinical psychopharmacology division. 9 Q. What were you doing, and -- 10 did you ever work on any other medications other 11 than Prozac up through say March, 1992? 12 A. This other antidepressant that 13 we mentioned. 14 Q. All right. We earlier 15 developed that for that first two-year period, 16 you spent sixty to seventy percent of your time 17 on Prozac, is that right? 18 A. That's correct. 19 Q. And then how about the second 20 period of time when you were a clinical research 21 physician, what period of time did you devote to 22 Prozac? 23 A. Approximately the same to 24 somewhat more. I continued to have Tomoxetine -- Page 25 1 Q. You weren't supposed to say 2 that. 3 A. -- experience through a great 4 deal of that period. 5 Q. Do you think that there was 6 ever any period of time that you devoted more 7 than seventy percent of your time to Prozac over 8 any given period? I understand that there might 9 have been days where you were working and maybe 10 even weeks that you were working exclusively on 11 Prozac work when it was hot. Can you 12 characterize that in any greater detail for me? 13 A. I think, again, during various 14 periods, it's hovered certainly in excess, 15 constantly in excess of fifty percent, 16 approaching eighty, ninety percent. Again, it's 17 difficult to characterize the specifics through 18 any period. I would characterize that as a 19 majority of time, but not exclusively. 20 Q. Who was your supervisor over 21 your work during the July, 1989, March 1992 time 22 period? 23 A. That would have been Doctor 24 Masica. Page 26 1 Q. The entire time? 2 A. Yes -- let's see, until -- 3 actually let me ask about the latter date that 4 you gave me. 5 Q. I understand you held the 6 title of clinical research physician from July, 7 1989 until March, 1992, is that right? 8 A. That's correct. Toward the 9 end of that, Doctor Gary Tollefson became my 10 management. 11 Q. And what was his job title? 12 A. He was executive director of 13 psychopharmacology. 14 Q. Did he replace Doctor Masica? 15 A. Yes, he did. 16 Q. What happened to Doctor 17 Masica? 18 A. Doctor Masica took -- was 19 assigned to another position within medical. I'm 20 not sure specifically what his job title was or 21 what his activities were. 22 Q. Is Doctor Masica still with 23 Lilly? 24 A. Yes. Page 27 1 Q. Do you know what his current 2 job title is? 3 A. No, I don't. 4 Q. Do you know what his last job 5 title was? 6 A. I know -- the last job title 7 I'm familiar with is the one when he was director 8 of clinical psychopharmacology. 9 Q. After March, 1992, what job 10 title did you assume? 11 A. Senior clinical research 12 physician. 13 Q. And what period of time did 14 you occupy that? 15 A. I still occupy that title. 16 Q. Since you became a senior 17 research physician, have you continued to work on 18 Prozac? 19 A. Yes. 20 Q. What percentage of your time 21 have you devoted to Prozac since you became 22 clinical research physician? 23 A. Well, actually, since 24 approximately November of 1991 I was assigned to Page 28 1 another compound in development, and have 2 extensively been assigned to that full-time. 3 There are residual -- well, as residual 4 Fluoxetine related activity that I'm still 5 somewhat involved with. 6 Q. In what capacity? 7 A. There was the completion of 8 the final report, and there are regular -- and 9 there are academic papers to be written, so I 10 will be involved in that aspect. 11 Q. The completion of the final 12 report, what final report? 13 A. The report of the results of 14 the study. 15 Q. On a particular clinical 16 trial? 17 A. Correct. 18 Q. All right. What trial is 19 that? 20 A. This was a long-term 21 maintenance trial. 22 Q. And has that trial been 23 completed? 24 A. Yes, it has been. Page 29 1 Q. And where are you in finishing 2 the final report? 3 A. The final report has been 4 completed and, I believe, submitted, actually, a 5 month or two ago. 6 Q. Submitted to who? 7 A. To the Food and Drug 8 Administration. 9 Q. Was that a depression trial? 10 A. Yes, it was. 11 Q. And how many patients 12 comprised that trial? 13 A. Beginning the trial, I think 14 close to a thousand patients began the trial. 15 Q. How many completed? 16 A. Actually existed at the end of 17 the trial on the last visit, I'm uncertain. 18 Q. Approximately what percentage 19 completed? 20 A. It's a complex trial. Of the 21 thousand patients, only approximately four 22 hundred were randomized. Of that, probably 23 something on the order of thirty percent of the 24 patients, between twenty and thirty percent of Page 30 1 the patients completed the final trial, between 2 twenty and thirty percent, approximately. That 3 was a year-long trial. 4 Q. Would that be thirty percent 5 of those four hundred randomized? 6 A. That's correct. 7 Q. Twenty to thirty percent. I 8 better quit talking to myself. Was this an 9 open-label study? 10 A. The twelve week lead-in period 11 prior to randomization was open treatment, then 12 patients received double-blind randomized 13 treatment. 14 Q. All right. What was the 15 comparator drug? 16 A. The comparator was placebo. 17 Q. What scales were used in that 18 study to measure suicidality? 19 A. In that scale there was the 20 Hamilton, including item three. 21 Q. Is that the only scale used -- 22 A. Yes, it was. 23 Q. -- that in any way touched on 24 the issue of suicidality? Page 31 1 A. Yes, it was. 2 Q. That was a year-long trial? 3 A. The double-blind portion was 4 actually sixty weeks, with a twelve week lead-in 5 period, and the time of entry of patients into 6 the trial was, I think, approximately fourteen 7 months. So it took fourteen months to begin the 8 nine hundred and eighty some odd patients. Each 9 of those patients then had the potential for 10 running twelve weeks, plus the rest up to sixty 11 weeks. 12 Q. Of the four hundred that were 13 randomized, how many were randomized to placebo 14 versus Prozac? 15 A. There was a complex 16 randomization process. There were four arms in 17 the double-blind period, so approximately a 18 hundred patients per arm -- not quite a hundred 19 per arm, basically a hundred. One arm went 20 immediately to placebo. Another group of 21 patients stayed on Fluoxetine for an additional 22 fourteen weeks, and then were randomized to 23 placebo. Another group stayed for fifty weeks, 24 and then went to placebo for the last twelve. Page 32 1 Another group stayed continuously on Fluoxetine. 2 Q. What was the purpose of that 3 trial? 4 A. The purpose of the trial was 5 to look at the capacity of Fluoxetine to maintain 6 a remission or a lack of depressive 7 symptomatology through this period, and with the 8 variable arms to assess something about the 9 optimal length of continuation therapy in 10 depression. 11 Q. So would you say that then 12 before the patients were randomized, they had to 13 demonstrate some improvement in their severity of 14 depression before they were randomized? 15 A. They had to in fact show 16 essentially remission or complete absence of 17 depressive symptoms. 18 Q. Measured by what? 19 A. Measured by the Hamilton scale 20 and the lack of meeting clinical criteria for 21 major depressive disorder. They had to achieve a 22 Hamilton score of seven or less. 23 Q. So once they achieved the 24 score of seven or less, they could be randomized? Page 33 1 A. They had to complete twelve 2 weeks, and during at least the last three visits 3 have scores that suggested that they had 4 clinically resolved their depression. 5 Q. And then at that point they 6 could be randomized? 7 A. Yes. 8 Q. And was that a multi-center 9 study? 10 A. Yes, it was. 11 Q. Who was the investigator on 12 that study? 13 MR. MYERS: Hold on, don't answer 14 that. There's a court order on that subject, and 15 what Judge Godich just said, he's not going to 16 answer that question. 17 MR. DOWNEY: There's a court order in 18 the Fentress case, but there's no court order in 19 the Saines case. 20 MR. MYERS: There's a very specific 21 and limited order in the Saines case, he's not 22 going to answer that question, so let's not argue 23 about it. 24 MS. ZETTLER: Find out if the Page 34 1 investigators were pivotal investigators, Larry. 2 MR. MYERS: You can read him the list 3 of pivotal investigators if you want, I don't 4 care, but he's not going to wholesale disclose 5 who the investigators were. 6 Q. Was the investigator an 7 investigator that had been used by Lilly in those 8 pivotal trials that were submitted to the FDA for 9 approval of Prozac? 10 A. I don't know all of the 11 pivotal investigators in what I understand to be 12 the second pivotal trial. 13 Q. The second pivotal trial? 14 A. That's correct. 15 Q. You mean the second pivotal 16 trial submitted to the FDA originally? 17 A. Correct, right. 18 MR DOWNEY: Let me make a record real 19 quick, Paul, for my case. You are refusing to 20 disclose the name of investigators in this trial? 21 MR. MYERS: Yes. 22 MR DOWNEY: And you're refusing to let 23 him disclose that? 24 MR. MYERS: Yes. Page 35 1 MR DOWNEY: Mark that for a motion in 2 my case because the court order in my case says 3 specifically that all clinical trial 4 investigators' names are to be disclosed. 5 MR. MYERS: I think you're probably 6 overstating the scope of that order, but we'll 7 let a judge rule on it. By the way, is there a 8 notice, Mr. Downey, for this deposition in the 9 Saines case? 10 MR. DOWNEY: Yes, what's his name, 11 Mister Morris -- 12 Q. Who was the medical monitor on 13 that trial? 14 A. I was the medical monitor. 15 Q. Well, do you know whether or 16 not the investigator that was on that trial was 17 an investigator who participated in any pivotal 18 studies that were submitted to the FDA? 19 A. I don't -- what I was trying 20 to say is I don't know the names of all the 21 pivotal -- 22 Q. That's fine. 23 A. -- investigators. 24 Q. But of those names of pivotal Page 36 1 investigators that you do know the names of, were 2 any of those individuals the investigator on this 3 trial? 4 A. The one name that I believe 5 was a pivotal investigator was not a participant 6 in this trial. 7 Q. Has a conclusion been reached 8 with respect to the results of that trial? 9 A. Yes, it has been. 10 Q. What was that conclusion? 11 A. That Fluoxetine administered 12 for up to sixty weeks is significantly more 13 effective than placebo in preventing recurrence 14 of depression, depressive symptoms. 15 Q. This study has been completed, 16 is that right? 17 A. That's correct. 18 Q. Were there any instances of 19 individuals in that trial who -- has that trial 20 been unblinded? 21 A. Yes, it has been. 22 Q. Were there any individuals who 23 experienced suicidal ideation during that trial? 24 A. There were clearly patients Page 37 1 who experienced increases in their suicidal 2 ideation as assessed by item three of the 3 Hamilton, as well as adverse event reports. 4 Q. Were there any individuals who 5 committed suicide? 6 A. I don't believe there were any 7 individuals that completed a suicide attempt, no. 8 Q. Were there any suicide 9 attempts? 10 A. There were suicide attempts, 11 yes. 12 Q. How many? 13 A. I'm not sure of the specific 14 number, less than ten, I believe. 15 Q. And of those ten, how many 16 were on Prozac? 17 A. I believe that all but one, 18 and it may have been all, I'm uncertain. 19 Q. So nine or ten of those 20 individuals who attempted suicide were on Prozac? 21 A. Again, the first number I said 22 I believe was less than ten. 23 Q. Okay. Was it close -- you 24 think ten is your best recollection of the number Page 38 1 that had attempted suicide? 2 A. I'm being conservative. My 3 best recollection is probably on the order of 4 five, but I -- 5 Q. Then why would you double it 6 by putting ten as your first estimate? 7 A. I'm uncertain and I wanted to 8 be conservative. 9 Q. Don't be that conservative 10 with me, Doctor Beasley. I'm going to be asking 11 you about numbers and things of that nature 12 throughout the three days of your deposition. 13 Don't ever double a number that you're unsure of, 14 all right? 15 A. Certainly. 16 Q. I'm going to caution you 17 against that. I want your answers to be 18 accurate. These matters are of significant 19 importance to us, as well as Eli Lilly and 20 Company, and if you were to double a number under 21 any circumstances, either favorable or 22 unfavorable, to either side, that would be 23 inaccurate and neither side wants that kind of 24 information, all right? Page 39 1 A. Certainly. 2 Q. Now, let me ask you the 3 question again. As I understand it, you said 4 that on this most recent trial that you 5 completed, where you were the medical monitor on 6 the Prozac trial, that was given to patients who 7 were on Prozac who had experienced a remission of 8 depression to be randomized on the trial, and 9 then were continued on the trial for 10 approximately fifty weeks, is that right? 11 A. That's correct. 12 Q. That of those individuals who 13 were randomized, that there were suicide attempts 14 that occurred during the course of that trial? 15 A. That's correct, including the 16 initial Prozac only open label lead-in period. 17 Q. How many occurred -- attempts 18 occurred during the open label Prozac initial 19 lead-in period? 20 A. I don't recall the specific 21 number. 22 Q. All right. How many occurred 23 after the patients were randomized? 24 A. I don't recall precisely the Page 40 1 specific number. 2 Q. Give me your best estimate. 3 A. My best estimate is that there 4 were approximately four during the initial 5 lead-in, and one during the double-blind portion. 6 Q. What will you have to do to 7 get us accurate information in connection with 8 that, Doctor Beasley? 9 A. I would need to look in the 10 final report. 11 Q. And you said the final report 12 has been completed? 13 A. That's correct. 14 Q. Is there a copy of the final 15 report at your office, I assume? 16 A. Not physically at my office, 17 that would be in the regulatory affairs area. 18 Q. That's something -- you don't 19 have a draft of it or something in your file? 20 A. No. 21 Q. Why? 22 A. As I completed it -- it's 23 completed in a separate area from where I am in 24 medical writing, and I don't keep a copy of it. Page 41 1 Q. Would this be something that 2 you could call somebody and get this information 3 for us? 4 A. Yes. 5 Q. Could we do that at a break? 6 MR. MYERS: We'll consider that at the 7 break. 8 Q. Would you have any problem 9 calling and getting that information at a break -- 10 A. No. 11 Q. -- if it's all right with your 12 lawyer? 13 A. No. 14 Q. All of those five individuals 15 were on Prozac at the time they attempted 16 suicide? 17 A. Again, I'm uncertain. 18 Q. But it's your best 19 recollection that they were all on Prozac? 20 A. That's correct. 21 Q. All right. Were 1639s filed 22 on each of those individuals? 23 A. I'm uncertain if they were. 24 If they were not serious adverse events, they may Page 42 1 not have been. 2 Q. Do you not consider an 3 attempted suicide a serious adverse event in 4 connection with Prozac, Doctor Beasley? 5 MR. MYERS: Hold on. Let me object to 6 the form and the use of the term serious because 7 that's a regulatory term. 8 MR. SMITH: That's the term he used. 9 MR. MYERS: I understand that. 10 Q. You can answer the question. 11 A. I was speaking from a 12 regulatory perspective. 13 Q. I'm asking you from your 14 perspective, do you not consider an attempted 15 suicide a serious adverse event in connection 16 with the use of Prozac, Doctor Beasley? 17 MR. MYERS: Same objection. Go ahead 18 and answer. 19 A. I think it's dependent upon 20 whether or not it's a transient gesture or a more 21 clinically serious event, that would really be an 22 individual clinical decision from case to case. 23 Q. All right. As the medical 24 monitor of this clinical trial, Doctor Beasley, Page 43 1 did you investigate any of these suicide 2 attempts? 3 A. I cannot recall my specific 4 actions regarding any of these attempts. 5 Q. Why is it that you cannot 6 recall that? 7 A. I'm sorry, but I can't, I have 8 no answer to your question as to why I can't 9 recall that, sir. 10 Q. Well, I guess I'm wondering 11 whether or not you made any investigations into 12 these five suicide attempts to determine any 13 details surrounding these attempted suicides. 14 A. We certainly have collected 15 information on them, that's why I know of their 16 occurrence, and I in fact know that there is 17 clinical descriptions of these in our final 18 report. 19 Q. All right. Would that be 20 contained in a specific portion of that final 21 report? 22 A. That's correct. 23 Q. Would that be contained or be 24 located in regulatory? Page 44 1 A. That's correct. 2 Q. Is this something that you 3 could find in that final report? 4 A. Yes, I could. 5 Q. Did you write it? 6 A. No, I did not physically put 7 pen to paper. 8 Q. Was it prepared under your 9 direction as the medical monitor, Doctor Beasley? 10 A. That's correct. 11 Q. Can you, if your attorney has 12 no objection, can you get that portion of that 13 final report that would give us the details of 14 those five, you think, attempted suicides? 15 A. Again, I point out that I'm 16 not certain, as I said before, the specific 17 number, but we could fairly easily put our hands 18 on that material, yes. 19 Q. And would you do that for us, 20 would you do that for us if your attorney has no 21 objection? 22 A. I would be happy to do that. 23 MR. SMITH: We would request that 24 either we take a long lunch break or discontinue Page 45 1 early this afternoon to give Doctor Beasley the 2 opportunity to get that for us if you're willing 3 to do that. 4 MR. MYERS: We'll consider that. 5 MR. DOWNEY: For the record, may I ask 6 Mister Myers was this report turned over to us? 7 MR. MYERS: I don't know if it was in 8 those fourteen or fifteen boxes or not, Mister 9 Downey, I don't know the answer to that question. 10 MR. DOWNEY: I was curious if you had, 11 thank you. 12 Q. You don't recall anything, 13 then, without looking at the report, about what 14 you might have done in connection with 15 investigating the particular facts or 16 circumstances of these number of suicide 17 attempts? 18 A. I would need to review the 19 reports. 20 Q. As we sit here today, do you 21 recall discussing any of -- as a clinical monitor 22 of this trial, discussing any of these particular 23 suicide attempts with the investigator? 24 A. No, I do not. Page 46 1 Q. Would this have been the same 2 investigator in connection with all of these 3 attempted suicides? 4 A. I don't believe so, I'm 5 uncertain. 6 Q. How many investigators did you 7 have on this trial? 8 A. Five. 9 Q. Five different sites? 10 A. Five different sites, that's 11 correct. 12 Q. Can you tell me where those 13 sites were? 14 A. There was Chicago, Salt Lake 15 City, New York. 16 Q. New York City? 17 A. New York City. Boston. 18 Q. Dallas? 19 A. Let me think about who the 20 investigator was. I don't recall the fifth one. 21 Q. And you don't recall doing any 22 investigation into the facts or circumstances 23 surrounding these approximately five suicide 24 attempts? Page 47 1 A. No. 2 Q. Do I take it by that, Doctor 3 Beasley, that as the medical monitor of these 4 trials you did nothing to determine whether or 5 not the suicide attempt was in any way related to 6 the patient's use of Prozac? 7 A. I'm terribly sorry, but as I 8 understand your question, you imply a particular 9 action or lack thereof on my part. 10 Q. Yes, I do. 11 A. I'm sorry, but I disagree with 12 that. What I'm saying is without me -- given 13 your warning earlier, without me being able to 14 sit here and actually recall the specific 15 conversations that I either had with the 16 investigator, absolutely, positively, or 17 directing the DEU or the clinical research 18 associate to gather additional information, I 19 believe that I can't make a specific statement 20 about what I did or didn't do. 21 Q. All right. Well, then, to put 22 it accurately, can you, as we sit here this 23 morning, think of anything you did to determine 24 whether or not the attempted suicide was in any Page 48 1 way related to the patient's use of Prozac? 2 A. We clearly conducted 3 statistical analyses at the end. In the open 4 label part, we had no comparative data to 5 compare. We clearly looked at item three of the 6 Hamilton, and we clearly looked at that as 7 information with regard to suicide in the trial. 8 Q. Do you recall anything other 9 than that that you did to make a determination 10 with respect to whether or not the suicide 11 attempt was in any way related to the patient's 12 use of Prozac? 13 A. Okay. Again, I cannot 14 specifically recall the exact precise actions 15 that I took in any of these clinical cases, 16 individual clinical cases. 17 Q. Was there anything in place, 18 Doctor Beasley, that was done as a standard 19 course when an adverse event, such as a suicide 20 attempt, occurred, by you, during the clinical 21 trials as the clinical monitor? 22 A. To that I can say yes, that we -- 23 as a routine policy that I endeavored to enforce, 24 we would attempt to follow up particularly on Page 49 1 suicides. Again, I cannot recall the specific 2 implementation of that intent, that policy. 3 Q. Okay. When you say follow up, 4 Doctor Beasley, what do you mean? 5 A. To gain the clinical 6 investigator's impressions and details around the 7 suicidal act. 8 Q. All right. So I assume that 9 one of the simplest and easiest things to do for 10 you or by you as a medical monitor on these 11 trials, if you saw a suicide attempt, would be to 12 pick up the telephone and say Doctor so and so, 13 as investigator and as the physician who was 14 treating the patient, do you have an opinion 15 concerning whether or not this particular patient 16 who attempted suicide did so by virtue of their 17 use of Prozac. Would that be correct? 18 A. Could you restate the question 19 for me again, please? 20 Q. I'll have her read it back for 21 you. 22 (QUESTION READ.) 23 A. I cannot, again, recall 24 inquiring of any of the physicians specifically Page 50 1 if they thought Fluoxetine was related in any way 2 to the suicide attempts. 3 Q. Would this be a question that 4 you would normally ask when you see something 5 like this? 6 A. No, it wouldn't. 7 Q. Why? 8 A. It's not something that I 9 routinely inquire of in these cases. 10 Q. Are you not interested in 11 knowing whether or not a patient who attempted 12 suicide during the clinical trial on Prozac that 13 you were the medical monitor on, attempted 14 suicide by virtue of the relationship -- by 15 virtue of their taking Prozac? 16 A. I'm clearly interested in 17 obtaining the factual information and details 18 around the case in the individual instance. If 19 that is something that is offered to me 20 spontaneously, it is an important piece of 21 information, it is not something that I have 22 routinely inquired about. 23 Q. Why? 24 A. The simplest reason is that I Page 51 1 feel that to do so might well prejudice the 2 clinician. 3 Q. Prejudice the clinician in 4 what way? 5 A. Bias him. 6 Q. In what way? 7 A. I'm not certain. 8 Q. Then why would you say that? 9 A. That's my position, and that's 10 what I think. 11 Q. Okay. You're telling me that 12 you're not going to ask the investigator what his 13 opinion is because you think it might bias him, 14 is that correct? 15 A. That's correct. 16 Q. In what way would it bias him 17 to ask him his opinion? 18 A. My sense is that it will 19 suggest the potential, the possibility. 20 Q. Wouldn't that be important to 21 know if a patient is taking a medication that 22 would cause him to attempt suicide? I mean this 23 is a human being that's consuming the medication. 24 Whether you bias the investigator or not, isn't Page 52 1 it important to make sure that you get the 2 impression of the investigator that's treating 3 that patient? 4 A. We've always attempted -- when 5 we have obtained information, we've attempted to 6 obtain detailed information in a very non-direct 7 fashion. 8 Q. Why don't you -- doesn't Lilly 9 hire these investigators that conduct these 10 trials? 11 A. They're paid on a 12 fee-for-service basis. 13 Q. But aren't they paid on a 14 fee-for-service basis by Eli Lilly and Company? 15 A. That's correct. 16 Q. Didn't you as the medical 17 monitor select those investigators? 18 A. I was involved in their 19 selection, yes. 20 Q. Weren't those investigators 21 psychiatrists? 22 A. That's correct. 23 Q. And weren't those 24 investigators psychiatrists that Lilly or you Page 53 1 felt were competent to treat individuals who were 2 depressed? 3 A. Yes. 4 Q. And weren't those 5 psychiatrists individuals in whom Lilly placed 6 some degree of competence in their judgment? 7 A. Yes. 8 Q. And didn't Lilly or you check 9 out the experience and clinical practice that 10 these investigators were involved in? 11 A. We certainly acquired their 12 curriculum vitae -- 13 Q. Didn't you in fact go talk to 14 them? 15 MR. MYERS: Paul, he's not finished 16 answering the question, let him finish. Go 17 ahead, Doctor. 18 A. And on many occasions, prior 19 to and certainly at start-up meetings, would go 20 speak with them, yes. 21 Q. You didn't have any 22 investigators on this trial in whom you didn't 23 have the utmost confidence in their ability and 24 training as a psychiatrist, did you, Doctor Page 54 1 Beasley? 2 A. To -- no. 3 Q. To administer a clinical 4 trial. 5 A. That's correct. 6 Q. Or to treat individuals who 7 were suffering the mental disorder of depression, 8 correct? 9 A. That's correct. 10 Q. So I'm at a loss to understand 11 if an individual who is being treated by these 12 physicians attempted suicide, you wouldn't find 13 it of some significance to know what the 14 physician who was treating the individual's 15 opinion was in connection with whether or not 16 that doctor felt that that particular individual 17 attempted suicide by virtue of their use of 18 Prozac? 19 A. Again, what I've said is I 20 cannot recall specifically asking a physician 21 whether or not they believed that an act had been 22 related to the medication. 23 Q. My question is, and I don't 24 understand, and maybe you can help me, Doctor Page 55 1 Beasley, is why wouldn't you ask that physician 2 that question, it's been a significant area of 3 concern, has it not? 4 A. Absolutely. 5 Q. And it is of significant 6 medical importance, is it not? 7 A. Certainly the issue is of 8 extreme medical importance. 9 Q. Because nothing could have 10 more serious ramifications than attempted suicide 11 or suicide, correct? 12 A. Absolutely. 13 Q. These were people who were 14 depressed and are sick, correct? 15 A. Absolutely. 16 Q. And if this medicine is 17 causing these depressed people and sick people to 18 attempt or commit suicide, that would be 19 extremely significant to the patient and to Eli 20 Lilly, wouldn't it? 21 A. It would, in fact, be very, 22 very serious to the patients and to Eli Lilly. 23 Q. And, so, why wouldn't you ask 24 the physician who was treating the patient why Page 56 1 they didn't have a -- what their opinion was in 2 connection with respect to whether or not the 3 Prozac was related to the individual's committing -- 4 attempting suicide? 5 MR. MYERS: I object to the question, 6 it's been asked and answered a couple of times. 7 Go ahead and answer it again. 8 A. What I've said is I cannot 9 recall any specific reason why, at the time, that 10 I can't recall not doing so, I cannot recall why 11 I did not. Sitting here in retrospect, 12 attempting to assess the issue, my statement is 13 that we attempted to collect information in a 14 very open-ended fashion. If that's something the 15 individual investigator wished to offer, we were 16 certainly extremely interested in it. We did not 17 direct the inquiry in that fashion. 18 Q. Did I understand you, though, 19 earlier, Doctor Beasley, to say it's not your 20 general practice when you see a suicide or a 21 suicide attempt to ask the investigator what the 22 investigator's opinion was in connection with the 23 relationship of the attempted suicide to the use 24 of Prozac? Page 57 1 A. That's correct. 2 Q. Do you recall any of these 3 investigators volunteering to you whether or not 4 it was their opinion that the use of Prozac was 5 related to the suicide attempt? 6 A. No, I do not. 7 Q. What else did you do or didn't 8 do -- well, I think we've established that you 9 don't recall asking any particular investigator 10 their opinion on this, correct? 11 A. That's correct, I don't recall 12 it. 13 Q. And it's not your general 14 policy to ask an investigator what their opinion 15 is on this, correct? 16 A. That's correct. 17 Q. What was done as a general 18 policy in making any determination concerning 19 whether or not this suicide attempt was related 20 to Prozac? 21 A. There were, again, as I 22 recall, a collection of information regarding the 23 events surrounding the case, a description of the 24 case. Page 58 1 Q. All right. In what respect, 2 what information would you collect? 3 A. Whatever the site offered, the 4 particulars, the time, the method, the outcome. 5 Q. Okay. Now you say whatever 6 the site offered in connection with time, method 7 or outcome? 8 A. Correct. A general 9 description of the case and circumstances 10 surrounding the case. 11 Q. Okay. How would that 12 information be conveyed to you as a medical 13 monitor? 14 A. Usually the site would call, 15 hopefully the site would call as opposed to 16 simply picking it up on documentation and case 17 report forms that we received. They usually 18 called the clinical research associate working on 19 the project, that individual would convey the 20 information to me. 21 Q. That's supposed to be 22 automatic, whenever something of the nature of a 23 suicide attempt happens, is the CRA is supposed 24 to get with you instantly, aren't they, or within Page 59 1 a reasonabe period of time? 2 A. Again, that depends on the 3 clinical circumstances. Clearly they're supposed 4 to get with me with any serious events, both in a 5 regulatory sense and anything that they would 6 think that I might think would be also clinically 7 serious. 8 Q. Wouldn't a suicide attempt 9 qualify as that, Doctor Beasley? 10 A. That's correct. 11 Q. So what happens once you get 12 word of a suicide attempt by the CRA? 13 A. Well, a number of things could 14 happen. 15 Q. Tell me. 16 A. Hypothetically? 17 Q. Well, is there any mechanism 18 in place to make a thorough investigation in 19 connection with an attempted suicide that occurs 20 during the clinical trials? 21 A. Absolutely. 22 Q. Is it written? 23 A. No. 24 Q. All right, then, what is it? Page 60 1 A. Not specifically for suicide, 2 and I'm not aware of any specific written policy 3 in this area. But obviously there is the 4 physician, the CRA and the drug epidemiology 5 unit, the CRAs are all available to follow up on 6 the event obtained, an adequate description of 7 the event, and report that to the Food and Drug 8 Administration. 9 Q. Now you've got to do that 10 because of the regulatory requirements of the 11 FDA, don't you? 12 A. That's one of the reasons it's 13 done. 14 Q. Okay. But I'm wondering what 15 specifically is done by Eli Lilly and Company to 16 investigate a particular suicide attempt. 17 A. In general, we attempt to 18 obtain as much possible clinical information 19 about the acute circumstances of the event, and 20 the patient in general. Again, with a patient 21 who is in a clinical trial, we have rather 22 substantial information about their ongoing 23 course, their activities, their demographics. 24 Q. You may very well have had Page 61 1 forty weeks of detailed information concerning 2 that patient, correct? 3 A. Correct. 4 Q. And when these individuals 5 come in on these clinical trials, this particular 6 clinical trial, this long-term efficacy study, 7 would that be accurate to call it a long-term 8 efficacy study? 9 A. Yes, a maintenance would be 10 the -- 11 Q. And you have a lot of 12 information on these patients, do you not? 13 A. That's correct. 14 Q. And do they see a psychiatrist 15 or see the investigator each week? 16 A. They see the investigators for 17 their evaluations. I'm uncertain as to whether 18 or not they would necessarily see a psychiatrist 19 at each visit. For example, I can think of one 20 site that used actually a single expert trained 21 clinical psychologist to rate the efficacy 22 portion of the trial. 23 Q. All right. But they're seeing 24 somebody trained -- Page 62 1 A. That's correct. 2 Q. -- in assessing individuals in 3 depressed states, are they not? 4 A. That's correct. 5 Q. And the monitor changes over a 6 period of time in their depressed state? 7 A. That's correct. 8 Q. So you have all that 9 information available to you -- 10 A. That's correct. 11 Q. -- in the clinical report 12 forms? 13 A. That's correct. 14 Q. In other words, you don't have 15 to get to the investigator's site to get the 16 background information on that patient, do you? 17 A. To get -- we have available to 18 us a great deal of background information. 19 Q. Because I would assume that's 20 submitted by the investigator to Lilly on a 21 weekly basis? 22 A. The case report forms are 23 filled out on a by-visit basis. 24 Q. But they're reflective of each Page 63 1 and every treatment up to that date, are they 2 not? 3 A. That's correct. 4 Q. And a suicide attempt, you 5 already have that, don't you? 6 A. That's correct. 7 Q. That you can look at. What 8 additional information do you get other than that 9 data that's reflected on an ongoing basis by the 10 case report forms? 11 A. You collect information 12 regarding the specifics of the attempt. 13 Q. Okay. Like did they use a 14 gun, overdose, jump off a bridge, whatever? 15 A. That's correct. 16 Q. All right. That would be the 17 mode or method of attempt, right? 18 A. That's correct. 19 Q. What else? 20 A. The outcome of the attempt. 21 Q. Life or death? 22 A. Or -- 23 Q. Hospitalization? 24 A. Or hospitalization, the Page 64 1 treatment that followed on the attempt. 2 Q. Do you recall of these 3 approximately five individuals that attempted 4 suicide while on Prozac during this long-term 5 trial, whether or not any of those individuals 6 were hospitalized as a result of their suicide 7 attempts? 8 A. I believe so, I believe more 9 than one, less than the total number. 10 Q. All right. How many? 11 A. I'm uncertain. 12 Q. Would it be more than twenty? 13 A. This is one that I would be 14 uncertain about. 15 Q. Would you have data about that -- 16 A. Yes. 17 Q. -- also in your final report? 18 A. That's correct. 19 Q. What other information would 20 you obtain? 21 A. There might or might not be 22 information regarding any potential psychosocial 23 precipitant, a sense of what caused the person to 24 take the action. Page 65 1 Q. Motive? 2 A. Sorry, but I don't think 3 that's quite the correct word. 4 Q. And again, don't let me put 5 words in your mouth, Doctor Beasley. 6 A. I'm thinking more about a 7 fight with a boyfriend or something like that, 8 fight with a girlfriend. 9 Q. All right. Is that something 10 that you attempted to determine in each instance 11 of attempted suicide? 12 A. In general, that's the type of 13 information we would like to obtain, yes. 14 Q. How do you communicate your 15 desire to obtain that information? 16 A. It's communicated to the site. 17 Q. How? 18 A. By an individual in medical, 19 be it myself, a CRA working on the project, drug 20 epidemiology. 21 Q. Do you recall in this study 22 whether or not you ever asked one of your 23 investigators in connection with one of these 24 approximately five suicide attempts to make a Page 66 1 determination with respect to whether or not 2 there was a psychosocial participant involved in -- 3 did I say something wrong? 4 A. Precipitant. 5 Q. Precipitant. 6 MR. MYERS: Mister Smith butchers some 7 terminology from time to time. 8 A. It's funny lingo. Again, I'm 9 terribly sorry, but I can't recall any specific 10 instance where I would have specifically asked. 11 Q. All right. Let me see if I 12 understand to get this clear, Doctor Beasley. As 13 we sit here today, do you recall talking with any 14 of the investigators regarding any of the 15 attempted suicides that occurred during this 16 clinical trial? 17 A. No. 18 Q. As we sit here today, do you 19 recall asking any of the particular investigators 20 of these approximately five suicides whether or 21 not those investigators thought that that suicide 22 attempt was related to Prozac? 23 A. No. 24 Q. Do you recall requesting any Page 67 1 specific investigator any specific information 2 concerning the specific attempted suicide in this 3 clinical trial? 4 A. No. 5 MR. MYERS: Can we take a break? 6 MR. SMITH: Yes. 7 (A SHORT RECESS WAS TAKEN.) 8 Q. Doctor Beasley, we've had 9 about a twenty-five minute break. Have you had 10 an opportunity to call your office -- 11 MR. MYERS: Excuse me, we've had about 12 a thirteen minute brake. 13 Q. Thirteen minute break. Have 14 you had an opportunity to call your office to 15 determine whether or not there were more than 16 five or less than five individuals on that study 17 that attempted suicide? 18 A. No, I have not. 19 MR. MYERS: I made a phone call, Paul, 20 and I don't have an answer, but I should hope to 21 have an answer by or immediately after the lunch 22 break. 23 MR. SMITH: All right. 24 Q. Now we were talking about the Page 68 1 fact that in checking on these attempted 2 suicides, that the investigator might have told 3 you about some precipitating factors in 4 connection with the particular suicide attempt, 5 is that right? 6 A. Might have told someone at Eli 7 Lilly. 8 Q. All right. Is that something 9 that would ordinarily be sought by Lilly or is 10 that something that would just be recorded if 11 volunteered by the investigator? 12 A. Again, it would be general 13 practice to follow up and collect relevant 14 clinical information, usually in a non-directed 15 fashion, and this would presumably be one of 16 those things that would be collected. 17 Q. When you say you would have a 18 follow up in a non-directed fashion, I don't 19 understand what you mean by that, Doctor Beasley, 20 and there may be others that don't understand 21 that. Could you help us with that, please, sir? 22 A. A call to the site requesting 23 as much information as they could provide us that 24 they felt was clinically relevant that we might Page 69 1 not otherwise have regarding the suicide. 2 Q. What do you mean when you say 3 non-directed fashion? 4 A. I just gave an example, it's a 5 general question regarding information on the 6 events. 7 Q. There's no written -- 8 A. No checklist. 9 Q. No checklist of information 10 that is required to be obtained from the 11 investigator, is that correct? 12 A. That's not entirely correct. 13 If a 1639 is filled out, there obviously are 14 certain specific categories for information. 15 Q. But a 1639 is an FDA document 16 that's got to be filled out by virtue of FDA 17 regulations, correct? 18 A. That's correct. 19 Q. All right. But in addition to 20 that information that's obtained on the 1639, 21 other information written that is requested in 22 attempted suicides by Lilly? 23 A. There's no specific checklist. 24 Q. Why is that? Page 70 1 A. I have no explanation. 2 Q. You have authored a 3 significant number of papers, have you not, 4 Doctor Beasley? 5 A. That's correct. 6 Q. And those papers have to do 7 with the relationship between Prozac and suicide, 8 correct? 9 A. That's correct. 10 Q. And attempted suicide and 11 Prozac? 12 A. That's correct. 13 Q. And suicidal ideation and 14 Prozac? 15 A. That's correct. 16 Q. And that information has been 17 disseminated to scientific personnel throughout 18 the country, has it not? 19 A. That's correct. 20 Q. Even your suicide experts that 21 you've consulted with from time to time have had 22 the benefit of your writings, have they not? 23 A. Our experts have clearly seen 24 our scientific papers. Page 71 1 Q. You submitted to them your 2 meta-analysis, have you not? 3 A. That's correct. 4 Q. But you have not asked any 5 investigator that you can recall any particular 6 request about any particular suicide attempt on 7 this latest long-term efficacy trial on Prozac 8 and depressed individuals? 9 A. I have indicated that I could 10 not recall doing so. 11 Q. Don't you think that would be 12 something that you would recall since this has 13 been something that you've written about 14 extensively, Doctor Beasley? 15 A. I'm sorry, but what I can say 16 to you is I don't recall. I'm not sure that I -- 17 I have no opinion on whether I would or would not 18 recall. 19 Q. Well, have you had any 20 difficulty recollecting facts in the past? 21 A. No. 22 Q. Do you have any problem with 23 your memory for which you're seeking medical 24 care? Page 72 1 A. No. 2 Q. Any complaint made by any of 3 your supervisors, such as Doctor Masica or any 4 others, concerning things that you've forgetten 5 at work? 6 A. No. 7 Q. Any other information that 8 might be obtained in a non-directed fashion by 9 Lilly concerning any particular suicide attempt? 10 A. Again, as I've said, the 11 circumstances around the act, the method, and the 12 outcome or clinical course following the attempt. 13 Q. Anything else that's obtained? 14 A. In general categories, I would 15 say that would be -- that, in itself, would cover 16 a wide amount of information. Of course anything 17 else that an investigator or site or reporter 18 would offer to us. 19 Q. Do you recall any instance in 20 an attempted suicide or suicide completed or 21 suicidal ideation where an investigator has 22 reported to you or other members at Eli Lilly and 23 Company that it was their opinion that the 24 attempted suicide or suicidality of any nature Page 73 1 was in any way related to Prozac? 2 MR. MYERS: This trial or any trial? 3 MR. SMITH: Any trials at any time. 4 A. And we're speaking about only 5 trials, or clinical investigations or spontaneous 6 reports as well? 7 Q. Arising out of the clinical 8 trials. 9 A. I don't recall -- I don't 10 recall any such reports from clinical trials. 11 Q. All right. Do you recall 12 reports from other sources? 13 A. Yes. 14 Q. All right. Tell me about 15 those. 16 A. Well, obviously the one that 17 comes to mind, the one that comes most strikingly 18 to mind, is Doctor Teicher's report. 19 Q. Did you ever talk to Doctor 20 Teicher, Doctor Beasley? 21 A. Yes, I did. 22 Q. All right. When did you talk 23 to Doctor Teicher? 24 A. I believe it was -- my first Page 74 1 occasion to speak with Doctor Teicher was 2 probably sometime in late January of 1990. 3 Q. Tell me about that 4 conversation. 5 A. We met with him in Boston. 6 Q. You said we, who was there? 7 A. Doctor Masica and I, and 8 Doctor Cole was present, as well as Carol Glod, I 9 believe is the pronunciation of her name. 10 Q. The co-author? 11 A. Yes. 12 Q. Carol Glod was co-author? 13 A. Yes, that is correct. 14 Q. Just the five of you? 15 A. I don't recall anyone else 16 being there, no. And Ms. Glod came in late, and 17 in fact Doctor Teicher came in after we met in 18 Doctor Cole's office, and he came in slightly 19 after we arrived. And Ms. Glod came in later. 20 Q. Doctor Cole, for the record, 21 had been a clinical investigator for Lilly, had 22 he not? 23 A. I believe that he had been. 24 Q. And Doctor Cole had been hired Page 75 1 by Eli Lilly and Company to do clinical trials on 2 Prozac, had he not? 3 A. I'm aware that he was an 4 investigator on a compassionate use protocol. 5 Q. On Prozac? 6 A. On Prozac. I'm unaware of 7 what specific comparative trials he might have 8 been a principle investigator or co-investigator 9 on. 10 Q. Did you know at the time or do 11 you know now, Doctor Beasley, that Doctor Cole 12 had -- that one of the patients mentioned in 13 Doctor Teicher's article was a patient of Doctor 14 Cole that was being treated on a Lilly Prozac 15 trial? 16 A. I wasn't aware that that was a 17 trial patient. 18 Q. Are you now? 19 A. Are you telling me that that 20 patient was a trial patient? 21 Q. Well, I'm not going to 22 represent any facts to you other than it's my 23 understanding that one of the patients that 24 Doctor Cole was treating, that was discussed in Page 76 1 Doctor Teicher's and Doctor Cole's article, was a 2 patient who had had severe suicidal ideation 3 while on a Prozac trial sponsored by Lilly, being 4 done at McLane Hospital by Doctor Cole? 5 A. I was not aware that that 6 patient was in a clinical trial. 7 Q. All right. Was the substance 8 of that discussion between you and Doctor Masica, 9 Doctor Teicher and Doctor Cole the subject of 10 suicidal ideation and its relationship to Prozac? 11 A. That's correct. 12 Q. And would it be accurate to 13 state, Doctor, that since that time, you've been 14 interested in the question? 15 A. Absolutely. 16 Q. What did Doctor Teicher tell 17 you his opinion was concerning whether or not 18 Prozac could cause suicidal ideation or 19 intensification of suicidal thoughts in depressed 20 individuals? 21 A. He was of the opinion that it 22 might be. 23 Q. What did Doctor Cole tell you 24 concerning that issue? Page 77 1 A. I don't recall Doctor Cole 2 making as explicit a statement in that 3 conversation. He was clearly a co-author of the 4 paper that described this phenomena. 5 Q. There's nothing in that paper 6 authored by Teicher and Cole and Glod that said -- 7 by the way, Doctor Cole is not as sure about the 8 findings that we report as Doctor Teicher is? 9 A. Absolutely not. 10 Q. And Doctor Cole didn't disavow 11 the opinions expressed in that article, did he? 12 A. No, he did not. 13 Q. Both Doctor Teicher and Doctor 14 Cole were cooperative during that meeting, were 15 they not? 16 A. Absolutely. 17 Q. This was a meeting of 18 scientists, correct? 19 A. It had that -- 20 Q. Flavor? 21 A. Perfect word. 22 Q. And it was cordial in all 23 respects, was it not? 24 A. Yes. Page 78 1 Q. Wasn't a shouting match? 2 A. No. 3 Q. You weren't going down there 4 and saying how could you say this about our good 5 product, were you? 6 A. No. 7 Q. And they weren't stark-raving 8 lunatics saying you've got a horrible product, 9 were they? 10 A. No. 11 Q. It was a scientific discussion 12 concerning a matter of serious medical import, 13 was it not? 14 A. That's correct. 15 Q. Doctor Teicher, at no time, 16 was uncooperative with you in this meeting, was 17 he? 18 A. No, sir. 19 Q. And he was willing to do 20 whatever was necessary to explore this issue 21 further, also, wasn't he? 22 A. Based on my recollection of 23 the conversation and the meeting, I can't say 24 that we discussed in detail about the potential Page 79 1 for follow up. We certainly discussed it 2 briefly, and he did not indicate that he would 3 not in any way be cooperative in collaborating 4 with us. 5 Q. There were discussions 6 concerning a collaborative investigation at that 7 time into the issue, was there not? 8 A. That's correct. 9 Q. And by the way, Doctor Teicher 10 at that time was an assistant professor of 11 psychiatry at Harvard medical school, was he not? 12 A. I believe that's the case. 13 Q. And he had at that time 14 impecable credentials concerning his training, 15 did he not? 16 A. I'm not intimately familiar 17 with Doctor Teicher's C.V., but I would -- 18 Q. I'm sorry, I didn't mean to 19 cut you off. 20 A. But I would assume that that 21 was the case given his academic position. 22 Q. Even though you Yalees and you 23 Harvard graduates have a little rivalry up there 24 to see who is one or two, not three or four, Page 80 1 isn't it? 2 A. He was in a very reputable 3 institution. 4 Q. And you had never, up to that 5 time, seen any criticism of Doctor Martin 6 Teicher, had you? 7 A. I wasn't aware of any, no. 8 Q. And you had no reason to 9 believe that he was anything but a well qualified 10 trained psychiatrist? 11 A. That's correct. 12 Q. And had done research in the 13 past in connection with psychiatric issues? 14 A. I wasn't aware of his research 15 work. 16 Q. Well, you are now, aren't you? 17 A. Yes. 18 Q. And he was well respected at 19 that time, was he not? 20 A. I don't have reason to believe 21 that he wasn't, no. 22 Q. And he was treating 23 individuals who presented complex psychiatric 24 problems, was he not? Page 81 1 A. That's correct. 2 Q. And was competent as far as 3 you know to treat those individuals, wasn't he? 4 A. That's correct. 5 Q. And he was quite knowledgable 6 at that time, as far as you knew, wasn't he, with 7 respect to psychopharmacology? 8 A. Again, I had no reason to 9 believe otherwise. I was not familiar with 10 Doctor Teicher, but I didn't have any reason to 11 doubt his competence or his ability. 12 Q. And frankly you don't now, 13 either, do you? 14 A. I have reason to doubt his 15 thoroughness as a scholar. 16 Q. All right. You don't have any 17 reason to doubt his motives or intent, do you? 18 A. No. 19 Q. I don't know how we got on 20 that. 21 MR. MYERS: You started it. 22 A. You asked -- 23 Q. Have you read Doctor Teicher's 24 latest article concerning suicide -- suicidality Page 82 1 and Fluoxetine, and antidepressant treatment in 2 general? 3 A. I have read more than one 4 article by Doctor Teicher. I'm not certain -- 5 I'm not certain that the last one that I read 6 would necessarily be his last. 7 Q. I'm referring specifically to 8 the longer work, other than the original American 9 Journal of Psychiatry, the one that was published 10 in New Zealand, I believe, by Atus, Etus? 11 A. I think we're thinking about 12 the same thing. 13 Q. Some drug research group? 14 A. I think we're thinking about 15 the same article. 16 Q. The publication is a reporter 17 on drug research, is that correct? 18 A. I don't recall the specific 19 name of the journal, it was not one that I was 20 familiar with. 21 Q. All right. But you've read 22 that latest article? 23 A. If -- I'm assuming we're 24 talking -- Page 83 1 Q. You read that article, whether 2 it be the latest or not? 3 A. Right. 4 Q. And did you have any 5 disagreement with that article? 6 A. As I recall, Doctor Teicher 7 laid out a number of hypotheses regarding 8 potential etiologic associations or potential 9 explanations of associations between 10 antidepressants and suicidality. 11 Q. Yes. 12 A. I do not recall specifically -- 13 and he laid out a number of hypotheses. Sitting 14 here today, I can't recall the -- I think it was 15 six, but I can't recall the specific details of 16 what those hypotheses were or which one he 17 particularly favored or disfavored. 18 Q. Do you recall whether you 19 agreed or disagreed with any of those hypotheses? 20 A. I thought that they were all 21 hypotheses and conjecture. 22 Q. Are you aware that Doctor 23 Teicher treats patients in his practice? 24 A. Yes. Page 84 1 Q. And sees patients who are 2 depressed? 3 A. Yes. 4 Q. And he's referred patients who 5 are depressed? 6 A. Referred to him, yes. 7 Q. And you, however, other than 8 that limited part-time clinical work that you 9 did, have not been treating patients since you 10 graduated from medical school? 11 A. Other than my residency? 12 Q. Yes. 13 A. That's correct. With, I 14 should say, one exception. I have a clinical 15 faculty appointment at the University of 16 Cincinnati. Most of my duties are in the 17 teaching of psychopharmacology to the residents. 18 During the first year after gradution, I did see 19 two patients in consultation for extensive 20 diagnostic review. 21 Q. So you have seen two patients 22 since you completed your training? 23 A. That's correct. 24 Q. Did you prescribe either one Page 85 1 of them Prozac? 2 A. No. 3 Q. Have you ever prescribed 4 Prozac? 5 A. No. 6 Q. But Doctor Teicher has. 7 A. Yes, that's my understanding. 8 Q. Any other reports that you've 9 seen or reviewed that have indicated a causal 10 link between Prozac and suicidality other than 11 that of Doctor Teicher? 12 A. There are a number of other 13 literature case reports which have at least 14 raised the possibility. 15 Q. All right. This is an article 16 that you read in medical journals? 17 A. That's correct. 18 Q. That have been published by 19 journals that have peer review committees? 20 A. That's correct. 21 Q. That is individuals respected 22 in the community who have reviewed those papers 23 to see that they're scientifically accurate with 24 respect to the issues that they raised? Page 86 1 A. For the most part, these are 2 letters to editors. I'm not sure precisely about 3 the peer review process for those journals or 4 letters to editor. 5 Q. But those articles that you 6 read other than case reports associating Prozac 7 and suicidality, the articles themselves would 8 have had to have passed peer review scrutiny, 9 would they not? 10 A. That's correct. 11 Q. And as far as you know, did? 12 A. That's correct. Again, I'm 13 not intimately familiar with the editorial and 14 review process for all the journals. 15 Q. You're pretty intimate and 16 pretty familiar with the review process for 17 several journals, though, are you not? 18 A. That's correct. 19 Q. Such as the British Medical 20 Journal? 21 A. That's correct. 22 Q. Your meta-analysis was 23 submitted on several occasions before it was 24 finally approved for publication, wasn't it? Page 87 1 A. I believe that it was accepted 2 after the first revision. 3 Q. All right. So it had to be 4 revised? 5 A. Yes. 6 Q. Before that peer review 7 committee would accept that publication for print 8 in their journal? 9 A. That's correct. 10 Q. Any other reports, Doctor 11 Beasley, that you're aware of associating Prozac 12 with suicidality? 13 A. Over and above the literature 14 reports? 15 Q. Yes. 16 A. I'm familiar with one report, 17 a spontaneous report, that as I recall was 18 initially received by one of my colleagues. 19 Q. Who? 20 A. Doctor Heiligenstein. And as 21 I recall this case -- actually it was two cases, 22 I believe. 23 Q. Then don't call it one report. 24 A. Okay. Page 88 1 Q. You said one spontaneous 2 report, now you're telling me it's two cases. 3 A. I believe it was a called by a 4 psychiatrist, a single call, reporting two 5 patients. 6 Q. Okay. 7 MR. MYERS: He was precise then in his 8 answer, so don't scold him. 9 MR. SMITH: I'm just cautioning him. 10 A. I've got several coaches, I 11 guess. Reporting, again, I believe two cases. 12 I'm very certain about the call, I believe it was 13 two cases. It could have been one case, but I 14 believe it was two. 15 Q. All right. 16 A. Okay. My recollection is that 17 these were completed suicides, and that the 18 reporting physician -- and the patients were, of 19 course, being treated with Fluoxetine. 20 Q. Prozac? 21 A. Yes. I'm sorry, I tend to 22 call it Fluoxetine. And that the clinician was 23 surprised by these cases, that he had never had a 24 suicide in his practice before or it had been a Page 89 1 long time since he had had a suicide in his 2 practice prior to these two cases, if it was two 3 cases. And he found this unusual, and that this 4 suggested some potential for him to wonder about 5 a potential relationship to the medication. 6 Q. All right. What did you do 7 about that? 8 A. Doctor Heiligenstein followed 9 up on this case, obtained clinical information, 10 filed this in the drug epidemiology unit, filing 11 a 1639, and this raised, I think, our collective 12 sense at the time about following suicides again. 13 Q. It raised a collective sense 14 about following suicide? 15 A. We -- as part of our ongoing 16 review of DEN review, all adverse events on a 17 periodic basis, and suicide would obviously be 18 one of those that we followed up on. 19 Q. When was this report? 20 A. I don't recall the date of the 21 report. 22 Q. Was it before or after the 23 Teicher article? 24 A. It was before the Teicher. Page 90 1 Q. All right. How long before 2 the Teicher article? 3 A. I'm sorry, but I don't recall. 4 Q. Was this a product -- at this 5 time was Prozac on the market? 6 A. Yes. 7 Q. So it wouldn't have been 8 during the clinical trial period? 9 A. It would have been after 10 approval, yes. 11 Q. So it would have been sometime 12 after December, 1987 -- 13 A. That's correct. 14 Q. -- and before January, 1990 15 when you first learned of the Teicher article? 16 A. That was correct. 17 Q. Because you knew about the 18 Teicher article before it was published, didn't 19 you? 20 A. Just before it was published. 21 Q. Because Doctor Teicher or 22 Doctor Cole, one, had called you or made inquiry 23 of Lilly earlier about whether or not Lilly had 24 had any of experience with suicidality? Page 91 1 A. I'm sorry, but your question 2 implies the method by which I personally learned 3 of the Teicher article. 4 Q. All right. 5 A. And that was not the method. 6 Q. How did you learn about it? 7 A. We received a preprint of the 8 article from, I believe, a sales representative 9 who had actually been at McLane -- I don't know 10 if it was actually specifically called a grand 11 round, but a presentation where he discussed his 12 report. 13 Q. McLane Hospital, how is McLane 14 Hospital rated as a psychiatric institution? 15 A. I can offer you a personal 16 opinion of what I presume to be a collective 17 opinion, which is that it's a very good, very 18 fine institution. I don't have a formal hospital 19 psychiatric survey system for it. 20 Q. But you know that McLane 21 Hospital is recognized as one of the finer 22 hospitals in the country -- 23 A. Absolutely. 24 Q. -- for treatment of Page 92 1 psychiatric patients, correct? 2 A. Absolutely. 3 Q. That's where Harvard Medical 4 School psychiatrists and people who teach 5 psychiatry practice clinical work, isn't it? 6 A. That's one of several 7 institutions. 8 Q. Right. In the Boston area? 9 A. Associated with Harvard. 10 Q. Okay. But were you aware that 11 Doctor Teicher had called Lilly before January, 12 when you learned about the Teicher article, and 13 asked Lilly what information they had on 14 suicidality since he had made this observation? 15 MR. MYERS: I object to the form. Go 16 ahead and answer if you know. 17 A. I don't recall one way or the 18 other. 19 Q. What is the status between you 20 and Doctor Heiligenstein? 21 A. Doctor Heiligenstein? 22 Q. Heiligenstein. Is he senior 23 or junior to you at Lilly? 24 A. We have, I think, Page 93 1 approximately the same total length of service, 2 and his title is also senior clinical research 3 physician. 4 Q. All right. Does he report to 5 you in any way? 6 A. No. 7 Q. Do you report to him in any 8 way? 9 A. No. 10 Q. So as far as you know, from 11 Lilly's perspective, you're equals within the 12 group? 13 A. That would be my 14 understanding, yes. 15 Q. Okay. So there was this 16 report from the psychiatrist -- was it a 17 psychiatrist, this reporting physician? 18 A. That's my understanding. 19 Q. There was a report from a 20 psychiatrist that was received by Doctor 21 Heiligenstein about a completed suicide in two 22 cases, correct? 23 A. I said I believe it's two 24 cases. Page 94 1 Q. And that this physician, this 2 psychiatrist, had felt that there was a link 3 between Prozac and suicide in those particular 4 patients? 5 A. If I may, my recollection is 6 that he reported it, and in reporting it, he 7 reported that it was of unusual quality to him, 8 and that raised in his mind this potential 9 question. 10 Q. All right. And Doctor 11 Heiligenstein reported that to you? 12 A. He made mention of it to me. 13 Q. And was there a discussion 14 between you and he concerning this issue? 15 A. In that I can recall him 16 mentioning it to me, yes, there was. 17 Q. What was the discussion or 18 tell me about the discussion? 19 A. I don't recall the details of 20 what we said about the case. 21 Q. Tell me what you recall, that 22 you recall being said? 23 A. Only that he mentioned the 24 case to me. Page 95 1 Q. Anything else? 2 A. No. 3 Q. Is that the first time you 4 became aware in any manner, in any way, that 5 anybody was raising the question concerning 6 suicide and the use of Prozac? 7 A. As I recall, yes. 8 Q. That was a bombshell out of 9 the blue to you at that time that somebody or 10 some institution or some agency or some 11 psychiatrist or doctor would raise a question 12 concerning whether or not there's a link between 13 Prozac and suicidality? 14 MR. MYERS: I object to the form and 15 the use of the term bombshell out of the blue as 16 being your terminology and not his. But go ahead 17 and answer it, Doctor. 18 A. Again, that was the, as I 19 recall, first time I became aware of this as an 20 issue. 21 Q. Whether it be an issue at all, 22 was that the first time anyone or any agency or 23 any group or any psychiatrist had ever raised 24 this as a question? Page 96 1 A. It's the first time that I 2 clearly know personally that it was raised. I am 3 aware of an analysis done prior to the approval 4 of Fluoxetine assessing the issue of suicidality 5 and any association or lack thereof with Prozac. 6 Q. All right. When was that 7 analysis done? 8 A. I do not recall the specifics 9 of the time of that analysis. 10 Q. Who did that analysis? 11 A. My understanding is that the 12 Lilly person in charge of or responsible for that 13 analysis was Doctor Joe Wernicke. 14 Q. But I take it that you weren't 15 aware of this analysis by Doctor Wernicke before 16 you had heard about this issue from this 17 psychiatrist that reported two suicides to you? 18 A. I'm not certain when I became 19 aware of that analysis. My understanding of the 20 analysis is in fact it did not suggest a 21 relationship. 22 Q. Well, I didn't ask you what 23 the analysis -- 24 A. Right. Page 97 1 Q. -- found. My question was 2 were you aware of the existence of that analysis -- 3 A. Again -- 4 Q. -- when you learned of this 5 from the psychiatrist? 6 A. I'm not sure when I became 7 aware of that analysis. 8 Q. Were you the medical monitor 9 of any clinical trials at that time when you 10 learned from that psychiatrist that there might 11 be an issue concerning Prozac and suicidality? 12 A. That's somewhat difficult to 13 answer because I cannot place precisely in time 14 the time of that report. I have been the medical 15 monitor for a number of Prozac studies. 16 Q. All right. When did you first 17 become a medical monitor of a Prozac study? 18 A. It was probably sometime in 19 the fall of 1987, after joining Lilly as I had 20 indicated. 21 Q. And have you continued to be a 22 medical monitor of Prozac studies in some 23 capacity since then? 24 A. Yes, up until the conclusion Page 98 1 of this last study. 2 Q. And it was just concluded, 3 what, last November, did you say? 4 A. I think actually the study, 5 patient participation, was probably over more 6 than a year ago. 7 Q. This is 1994, so it would have 8 been completed in 1992 or '93? 9 A. In that time frame. 10 Q. How many clinical trials have 11 you monitored concerning Prozac, for any 12 indication? 13 A. Approximately ten. 14 Q. Approximately how many 15 patients were involved in those ten clinical 16 trials that were randomized? 17 A. Well, two of the trials did 18 not involve randomization. 19 Q. Okay. 20 A. I would be speculating within 21 orders of magnitude if I give you a number. 22 Q. Can you give me a reasonable 23 estimate on the number of patients? 24 A. The largest study was clearly Page 99 1 the long-term study which randomized four 2 hundred. All the rest of the trials have been 3 substantially smaller than that, probably on the 4 order of -- again, that involved randomized 5 treatment, on the order of twenty-five patients 6 per arm. 7 Q. So how many would that be 8 approximately, total? 9 A. Patients treated with 10 Fluoxetine -- 11 Q. Yes. 12 A. -- in randomized arms? 13 Probably something on the order of six hundred 14 randomized. And again, I'm estimating. 15 Q. How many individuals on Prozac 16 in all those ten trials, of those six hundred 17 patients, committed suicide? 18 A. I don't know. 19 Q. Give me your best estimate. 20 A. It would be speculative for me 21 to say. 22 Q. Can you give me an estimate 23 based on some degree of reason? 24 MR. MYERS: An estimate of? Page 100 1 MR. SMITH: Number of patients who 2 committed suicide on Prozac clinical trials in 3 which he was the medical monitor, patients were 4 ingesting Prozac. 5 MR. MYERS: Was the number six hundred 6 the number of patients that were randomized or 7 randomized to Prozac. He might have said that, I 8 don't know. 9 MR. SMITH: I assumed it was 10 randomized to Prozac. 11 A. It was randomized to Prozac. 12 Again, I'm not talking about also trials that had 13 no randomization. 14 MR. MYERS: Okay, I'm sorry. 15 A. I believe the number was zero. 16 Q. You believe the number is 17 zero, you had no suicide attempts on any trials? 18 A. I said suicides. 19 Q. I mean suicides. How about 20 suicide attempts? 21 A. Suicide attempts, I could not 22 estimate. 23 Q. Give me your best estimate. 24 A. I can't estimate a number. Page 101 1 Q. We know it's probably more 2 than five, don't we? 3 A. That's correct. 4 Q. Because we know of five that 5 occurred in the one trial that was just 6 completed, right? 7 A. Again, that was an estimate 8 for that one trial. 9 Q. Yes. But the five or 10 approximately five that occurred in the last 11 trial wasn't the first time and only trial that 12 you'd seen attempted suicides in, was it, in 13 which you had been a medical monitor? 14 A. Again, it would be speculative 15 for me to answer. 16 Q. You just can't give me any 17 number greater than five, Doctor Beasley? 18 A. No. 19 Q. Do you recall any instance of 20 attempted suicides in any other clinical trials 21 in which you were the medical monitor other than 22 this latest trial, long-term efficacy trial, and 23 it's been just completed? 24 MR. MYERS: And which the patient was Page 102 1 on Prozac? 2 MR. SMITH: Yes. 3 A. Randomized to Prozac? 4 Q. Yes. 5 A. Again, right now, right here, 6 I cannot recall a specific instance of such an 7 event. 8 Q. You're not saying that the 9 event didn't occur at all, are you? 10 A. Absolutely not. 11 Q. And more than likely, some 12 suicide attempts did occur, didn't they? 13 A. They may have, but I would not 14 put a probability figure on that. 15 Q. What would you have to do, 16 Doctor Beasley, to know the number of individuals 17 that attempted suicide on clinical trials that 18 you had been the medical monitor on while taking 19 Prozac, what would you have to do? 20 A. It would be to go back and 21 search the clinical trial data base. 22 Q. You haven't kept reports 23 concerning this issue as you progressed through 24 your work as a medical monitor research physician Page 103 1 at Eli Lilly and Company? 2 A. We certainly keep extensive 3 reports on this issue. I do not personally keep 4 a list of suicide attempts or completed suicides 5 through these trials. 6 Q. Well, whether you keep a list, 7 do you keep a cumulative total of numbers? 8 A. No, these are kept in our 9 computer data base. 10 Q. Well, these five that you had 11 in your most recent long-term use clinical trial, 12 wasn't the first time you had seen that as a 13 medical monitor, was it? 14 A. You know, again, I cannot 15 recall the specific instances in which I may or 16 may not have seen suicide attempts reported in 17 these clinical trials for which I was the 18 monitor. I have clearly seen many reports of 19 suicide attempts in my work with Fluoxetine. 20 Q. I understand that. I'm 21 talking about your experiences as a medical 22 monitor in which as many as six hundred 23 individuals were randomized to Prozac. 24 A. Again, I cannot recall Page 104 1 specific instances where I have seen this. 2 Q. You're not saying that that 3 hasn't occurred at all, are you? 4 A. No, I'm not. 5 Q. Did you do anything else in 6 investigating any other potential attempted 7 suicides during clinical trials other than what 8 you told me earlier that was done in connection 9 with the long-term efficacy study? 10 A. I can't recall any specific 11 activities in these clinical trials with regard 12 to potential attempted suicides. 13 Q. Do you know whether or not any 14 other medical monitors on any other clinical 15 trials of Prozac at Eli Lilly did any more or any 16 less in connection with investigating the 17 causality between Prozac and an attempted suicide 18 or completed suicide than you did? 19 A. I'm not aware of the specific 20 activities of other clinical monitors in this 21 area who have worked with Prozac. 22 Q. So would the answer to my 23 question be no, I don't know of any other 24 differences that they did that I might have done? Page 105 1 A. That's correct. 2 Q. Were there other clinical 3 monitors of other clinical trials in existence at 4 the time you were a clinical monitor -- medical 5 monitor of a clinical trial? 6 A. For Prozac? 7 Q. Yes. 8 A. Yes. 9 Q. Who were some other medical 10 monitors of Prozac clinical trials while you were 11 a medical monitor of Prozac clinical trials? 12 A. There was Doctor 13 Heiligenstein, Doctor Wheadon, Doctor Goldstein. 14 I don't recall whether Doctor Wernicke would have 15 been, he had been a medical monitor for 16 Fluoxetine and was still at Lilly when I was at 17 Lilly. 18 Q. Do you know of anything that 19 any of these individuals were doing investigating 20 attempted suicides or suicides other than what 21 you were doing? 22 A. Again, I'm aware that Doctor 23 Wernicke had conducted or participated in the 24 conduct of an analysis based on -- Page 106 1 Q. I'm sorry? 2 A. Based on clinical trial. 3 Q. Have you seen that analysis 4 that Doctor Wernicke did? 5 A. I've seen the report and 6 correspondence concerning it. 7 Q. Okay. You've seen the report 8 that Doctor Wernicke did? 9 A. Yes. 10 Q. Do you know if that report was 11 submitted to the Food and Drug Administration? 12 A. I don't know if it was or was 13 not. 14 Q. Should that have been 15 something that would ordinarily be submitted to 16 the Food and Drug Administration? 17 A. I don't know. 18 Q. Why don't you know that? 19 A. I'm not sufficiently 20 conversant with the regulatory requirements with 21 regard to supplemental documentation to know 22 definitely one way or the other. 23 Q. Doesn't your work as a medical 24 monitor of a clinical trial for Eli Lilly and Page 107 1 Company require you to be conversant with the 2 regulations with respect to what should be 3 reported to the Food and Drug Administration in 4 connection with an adverse event experienced on 5 Prozac? 6 A. With regard to an adverse 7 event, yes, absolutely. 8 Q. Aren't these -- isn't this 9 what Doctor Wernicke was doing in the analysis 10 concerning adverse events reported during 11 Fluoxetine therapy? 12 A. Well, I would believe that the 13 reports of all of these suicidal acts that had 14 been included were in fact reported to the FDA. 15 Q. No, I'm talking about -- 16 MR. MYERS: Let him finish. 17 Q. I'm talking about the analysis 18 made by Doctor Wernicke. 19 MR. MYERS: Finish your answer before 20 you answer that next question if you were not 21 done. 22 A. Well, I was actually going to 23 follow up with the answer to that question. 24 Q. I was trying to clarify what Page 108 1 my question was. 2 A. Which was -- again, I'm not 3 aware of that report being submitted or not. I 4 don't personally feel sufficiently conversant 5 with the law and the regulations to know whether 6 that would be required or not. 7 Q. All right. Other than that 8 report by Doctor Wernicke, are you aware of 9 anything that any of these other medical monitors 10 were doing at the time you were a medical monitor 11 any differently in connection with the issue of 12 Prozac and attempted suicide or suicides? 13 A. I believe that quite recently 14 trials that Doctor Heiligenstein had initiated 15 have included an additional suicidal ideation 16 questionnaire. This may have been included in 17 trials initiated by other monitors quite 18 recently, new monitors, but I'm only aware of 19 Doctor Heiligenstein including this in a clinical 20 trial recently. 21 Q. When you say recently, are you 22 talking this year, 1994? 23 A. Not 1994. 24 Q. 1993? Page 109 1 A. 1992, 1993. 2 Q. Of course Doctor Wernicke had 3 written on this subject back in the '80s, had he 4 not? 5 MR. MYERS: What subject? 6 MR. SMITH: This analysis concerning 7 suicidality and Prozac. 8 A. Well, I had -- I believe 9 that's what I indicated in response to who had 10 done -- who had been a monitor that had done 11 something, and I indicated that Doctor Wernicke's 12 analysis was something. 13 Q. And you had received this 14 report from this physician, this psychiatrist, 15 back after Prozac was on the market, but before 16 the Teicher article, where that psychiatrist had 17 suggested a potential question in connection with 18 this issue? 19 A. Not personally, no, but Lilly -- 20 Q. Through Doctor Heiligenstein -- 21 A. Right. 22 Q. -- it was reported to you? 23 A. Correct. 24 Q. Did you or Doctor Page 110 1 Heiligenstein talk to that physician? 2 A. Oh, yes, Doctor Heiligenstein 3 did. 4 Q. Did you? 5 A. No. 6 Q. Why is it that they're just 7 now being included, some suicidal ideation 8 questionnaire, when this issue came up much 9 earlier? 10 A. The timing of this has grown 11 out of the upsurge, not recently, in reports. 12 Wheadon isolated reports that we reported to the 13 FDA, took note of, but clearly the issue has been 14 something that we evolved progressively and much 15 more rapidly after Doctor Teicher's publication. 16 Q. My question was, since this 17 issue had come up before Doctor Teicher's 18 article, why hadn't there been some 19 implementation of some suicidal ideation 20 questionnaire earlier? 21 MR. MYERS: I object to the question, 22 he just answered it. Go ahead and answer it 23 again. 24 A. There was attention paid to Page 111 1 suicide with the acquisition of our spontaneous 2 reports. It was certainly something that was 3 attended to in clinical trials with adverse 4 events reports, and with a question on the 5 Hamilton, the clear impetus to increase activity 6 in this area clearly followed Doctor Teicher's 7 report. 8 Q. All right. So if Doctor 9 Teicher hadn't raised the question, we might 10 still not have a suicidal ideation questionnaire 11 being employed in your clinical trials, is that 12 correct? 13 A. That will be speculation on an 14 alternative future on my part. 15 Q. But up to Teicher, you had 16 never recommended such a questionnaire, did you? 17 A. No. 18 Q. And how many adverse reports 19 or reports of adverse experiences concerning 20 suicidality would there have had to have been 21 before Lilly instituted a change where they 22 submitted a suicidal ideation questionnaire to 23 individuals participating in their clinical 24 trials? Page 112 1 MR. MYERS: I object to the form. Go 2 ahead and answer. 3 A. Quite frankly, I don't know. 4 There would have -- I don't know. 5 Q. How many reports of suicide, 6 of completed suicides have there been up to date 7 in connection with people using Prozac, Doctor 8 Heiligenstein -- Doctor Beasley? 9 A. I don't know. 10 Q. You don't? 11 A. No. 12 Q. What is the last figure you 13 saw of individuals who had committed suicide 14 while on Prozac? 15 A. Completed suicides on Prozac, 16 I don't recall. 17 Q. Approximately? 18 A. I don't recall. 19 Q. Have you ever seen any figures 20 in that connection? 21 A. Absolutely. 22 Q. Okay. 23 A. I have -- 24 Q. What were they? Page 113 1 MR. MYERS: Go ahead. 2 A. I don't recall. 3 Q. Can you give me an 4 approximation? 5 A. Orders of magnitude meaning 6 ones or tens or hundreds, I would believe that it 7 would be in the hundreds but again I'm 8 speculating. 9 Q. Well, to be honest, it's in 10 the thousands, isn't it, Doctor Beasley? 11 A. I have not looked at the 12 cumulative DEN reports for Prozac in over two 13 years. 14 Q. Why? 15 A. Because that has not been my 16 responsibility. 17 Q. Do you not have any interest 18 in this issue any longer, Doctor Beasley? 19 A. I certainly do. 20 Q. Then why wouldn't it be of 21 interest to you to know how many people had been 22 reported to commit suicide while using Prozac? 23 MR. MYERS: Object to the form, that's 24 not what he said. Go ahead and answer. Page 114 1 A. Because I have basically from 2 that no comparative data whatsoever, there is 3 nothing for me to compare that number to other 4 than historical controls. 5 Q. Why? Why don't you have a 6 comparator number? 7 A. Because those patients are 8 not -- those patients are not randomly assigned 9 to Prozac versus a group of patients placed on 10 some alternative treatment or no treatment, 11 they're followed in a randomly assigned and 12 followed systematically to see what happens to 13 the two groups, there's no comparative data. 14 Q. Aren't you interested in 15 people committing suicide while on Prozac, Doctor 16 Beasley? 17 A. Those are tragedies. 18 Q. It's a tragedy of significant 19 proportions if it's in the hundreds or thousands, 20 isn't it? 21 A. Absolutely. 22 Q. It's a tragedy if it's one 23 person. 24 A. It's a tragedy if it's one Page 115 1 person. 2 Q. So there's no doubt in your 3 mind concerning the significance of this issue, 4 correct? 5 A. The individual clinical 6 significance of these is substantial. 7 Q. All right. And if even one 8 individual committed suicide as a result of 9 Prozac, that would be a tragedy also, wouldn't 10 it? 11 A. If I may expand, any 12 individual who commits suicide for whatever 13 reason is a tragedy. 14 Q. But especially as medical 15 monitor and as being a physician employed by Eli 16 Lilly and Company, it would be a significant 17 tragedy if an individual committed suicide by 18 virtue of their ingestion of Prozac, wouldn't it? 19 A. It would be. 20 Q. And that would be something 21 that you would be compelled to advise your 22 superiors at Eli Lilly of, wouldn't it? 23 A. That's correct. 24 Q. It would be something that you Page 116 1 would feel compelled to advise individuals at the 2 Food and Drug Administration? 3 A. Correct. 4 Q. And would be compelled to 5 advise individuals in regulatory bodies 6 throughout the United States? 7 A. That's correct. 8 Q. Don't you think that if one 9 individual committed suicide as a result of 10 ingestion of Prozac, that physicians throughout 11 the country prescribing Prozac should know that? 12 A. If that were the case? 13 Q. Yes. If you had made a 14 determination from a scientific standpoint that 15 one individual committed suicide as a result of 16 their taking Prozac, wouldn't you feel compelled 17 to advise other physicians of this? 18 A. Yes. 19 Q. And wouldn't you be compelled 20 to advise physicians who were prescribing Prozac 21 to patients in this country that that had 22 occurred? 23 A. Yes. 24 Q. And wouldn't you want to warn Page 117 1 them of this one instance where it occurred? 2 A. Yes. 3 Q. It would be necessary to do 4 that, wouldn't it? 5 A. Yes. 6 Q. So that the physicians could 7 have that information concerning that one suicide 8 while on Prozac in making the decision with 9 respect to whether or not to give the product to 10 their patients, correct? 11 MR. MYERS: Let me object to the form 12 of the question. You have gone from caused by 13 Prozac to while on Prozac, and I don't know if 14 it's the same question or not. 15 MR. SMITH: I didn't intend to imply 16 that, it's caused by Prozac. 17 MR. MYERS: Because the question needs 18 to be changed. Go ahead. 19 A. Yes. 20 Q. The reason for that, is it 21 not, Doctor, that with respect to advising 22 physicians who prescribe Prozac that a completed 23 suicide is of such a serious nature that if it's 24 just one completed suicide that occurs by virtue Page 118 1 of the ingestion of Prozac, that physicians 2 should be advised of this? 3 A. That that had occurred? 4 MS. ZETTLER: Read that back. 5 (THE COURT REPORTER READ BACK THE 6 REQUESTED TESTIMONY.) 7 A. Yes. 8 Q. So there wouldn't have to be 9 any statistical significant numbers concerning 10 causal connection between Prozac and suicide if 11 it were indeed just one person? 12 A. If one had definitive, 13 absolute -- your statement that it caused, taking 14 as an absolute statement? 15 Q. Yes. 16 A. I would agree. 17 Q. We have -- you've used the 18 term statistical significance in papers you've 19 written concerning suicide, have you not? 20 A. That's correct. 21 Q. We've deposed Lilly 22 statisticians who have used the term statistical 23 significance. Will you take our word for that? 24 A. I'm -- Page 119 1 MR. MYERS: You can. 2 Q. All right. And from a 3 standpoint of statistical significance, it 4 doesn't make any difference how many individuals 5 are on Prozac if one individual in fact committed 6 suicide as a result of Prozac, does it? 7 A. May I ask again that you're 8 presuming absolute causality? 9 Q. Yes. 10 A. Then I would agree. 11 Q. Well, causality as absolutely 12 as it can be determined from a medical 13 standpoint? 14 MR. MYERS: Is that a question? 15 MR. SMITH: Yes. 16 Q. The issue of statistical 17 significance is of interest in statistics only, 18 isn't it? 19 A. Absolutely not. 20 Q. Well, in what interest is 21 statistical significance important? 22 A. Statistical significance is a 23 comment, reflection, a suggestion of an 24 association. Page 120 1 Q. All right. Let me ask you 2 this, Doctor Beasley: Is statistical 3 significance more significant than what that 4 physician who reported to you these two suicides 5 with Doctor Heiligenstein, is that statistical 6 significance more significant to you than what he 7 had reported to you? 8 MR. MYERS: Statistically? 9 A. Important -- 10 MR. SMITH: Significantly. 11 A. Important in terms of -- 12 Q. Determining causation. 13 A. Oh, absolutely. 14 Q. You favor statistics over what 15 this physician reported to you in determining 16 whether or not Prozac caused a patient's 17 attempted suicide or completed suicide? 18 A. That's correct. 19 Q. You would defer to the 20 statisticians rather than the physician that 21 reported it to you? 22 A. I think you asked me about a 23 relative comparison of importance of data. 24 Q. All right, okay. Page 121 1 A. And what you asked me about 2 was one physician's report of an event. 3 Q. Yes. 4 A. Okay. And a temporal 5 association of that event with ingestion of 6 Fluoxetine. 7 Q. And his medical opinion that 8 he thought they were related. 9 A. He added that? 10 Q. Yes. 11 A. Okay. Versus finding or lack 12 of finding of an association between Prozac and 13 suicidality in a controlled data base, and the 14 latter is more important to me in helping me to 15 ultimately understand association. 16 Q. So in making a determination 17 with respect to -- with respect to the 18 association of Prozac and suicidality, you're 19 going to look at the statistics as opposed to 20 what a physician who was treating a patient might 21 report to you, is that correct? 22 MR. MYERS: I object to the form. Go 23 ahead and answer. 24 A. Again, you suggested that it's Page 122 1 either/or. I don't view it in that fashion. One 2 takes totality of data in understanding a 3 situation. A case report form, case reports, 4 anecdotal case reports form one piece of data 5 that may well suggest a need for additional 6 activities, such as a large statistical analysis. 7 Q. Would that one piece of data 8 be significant to you, that is that a physician 9 reported to you that it was his opinion that the 10 Prozac was the cause of the patient's taking 11 their lives? 12 A. I would take note of that, I 13 would bear it in mind. It would not -- obviously 14 it's a tragic event. It would not necessarily 15 compel me to undertake any specific actions over 16 and above what is already in place to review 17 suicide as one of the many adverse events. 18 Q. So is that a way of saying 19 you're going to look at the statistics? 20 A. Yes. 21 Q. And then make a determination 22 with respect to a cause in a particular instance? 23 A. Weighing total data in terms 24 of making a personal decision about causality? Page 123 1 Q. Yes. 2 A. Yes. 3 Q. That is you're going to look 4 at statistics? 5 MR. MYERS: I object to the form, 6 that's not what he said. He answered your 7 question. 8 Q. Well, as I understand it, 9 Doctor Beasley, you've never treated a patient 10 that was on Prozac, have you? 11 A. That's correct. 12 Q. And you've never had a patient 13 that's become suicidal while on Prozac? 14 A. That's correct. 15 Q. Because you never had a 16 patient taking Prozac, have you? 17 A. That's correct. 18 Q. If a physician who has been 19 treating patients, a number of patients, on 20 Prozac, reports to you I've had a patient who I 21 believe committed suicide as a result of their 22 taking Prozac, are you going to say he's wrong 23 because from a statistical standpoint you have 24 not come to a conclusion that there's a Page 124 1 relationship between suicide and Prozac? 2 A. I'm going to say that I 3 personally do not believe he's correct. 4 Q. So you're saying in your 5 opinion that psychiatrist is wrong, is that 6 right? 7 A. That's correct. 8 Q. He's made a mistake, is that 9 right? 10 MR. MYERS: You need to say yes or no. 11 A. Sorry about that. If the data 12 and the statistics are sufficient and robust, the 13 answer is yes. 14 Q. So in that instance, you are 15 deferring to statistics over and above that 16 opinion of a treating physician? 17 MR. MYERS: I object to the form. Go 18 ahead and answer. 19 A. I have taken the physician's 20 report to me into account, I place greater faith 21 in controlled data to suggest whether or not 22 there is an association between Prozac and any 23 event, or any other compound for that matter, 24 associated with a particular behavior. Page 125 1 Q. Is there any data that you've 2 seen that suggests that Prozac is related to any 3 adverse event, Doctor Beasley? 4 A. You're now asking me about 5 statistical -- 6 Q. You used the term data. Is 7 there any data available that you've seen that 8 suggests that Prozac causes any particular 9 adverse event? 10 A. Okay. There are clearly 11 statistically significant associations between 12 Prozac and a number of adverse events relative to 13 the placebo base rates. 14 Q. Such as? 15 A. Nausea is one that comes very 16 much to mind. 17 Q. What else? 18 A. Depending upon the data base, 19 headache. 20 Q. How about nervousness? 21 A. It's one. Nervousness -- and 22 again, I would characterize nervousness as one 23 that in some data bases has been reported to be 24 statistically significantly more associated, as Page 126 1 has sedation. 2 Q. How about agitation? 3 A. Depending upon the data base 4 that one looks at, yes, possibly. This is a 5 subject that I've actually written on. 6 Q. I know that, we're going to 7 talk about that. Don't believe for an instance, 8 Doctor Beasley, we're not going to get to that. 9 A. Rather substantially. 10 Q. How about anxiety? 11 A. And again, depending upon the 12 data base, yes. 13 Q. How about akathisia? 14 A. I don't believe that that has 15 ever reached, in and of itself, statistical 16 significance. 17 Q. Do you not believe that Prozac 18 can cause a worsening of akathisia or can cause 19 akathisia? 20 A. I don't know whether it can or 21 can't. My answer here is actually rather 22 complex, and I would be happy to -- 23 Q. It won't be the first time 24 I've heard a complex answer in this litigation. Page 127 1 A. Again, particularly since this 2 is an area that I have particular interest. 3 Q. The question simply is: Do 4 you consider akathisia as an event that is 5 significant -- has a significant association 6 between Prozac and the event? 7 A. I'm not sure that akathisia 8 with all that it connotes is an appropriate term 9 for what is associated with Prozac, and that's 10 reflected in a lengthy response of mine to an 11 article published by a group at Columbia 12 discussing akathisia with Prozac. 13 Q. What, the Worshing's article? 14 A. No, it would be the Hopper 15 Hamilton article. 16 Q. Have you reviewed the Worshing 17 article? 18 A. Yes. 19 Q. Do you agree or disagree with 20 that article? 21 A. I certainly have no reason to 22 disagree or dispute the clinical observations. 23 The labeling of that as akathisia, the clinical 24 phenomena that he describes, I have some Page 128 1 questions about and some issues with. In fact, I 2 have published disagreeing with that reference. 3 Q. Do you consider yourself an 4 expert on akathisia, Doctor Beasley? 5 MR. MYERS: I'm going to object to the 6 form only to the extent the term, quote, unquote, 7 expert may have some legal significance. But go 8 ahead and answer it if you can. 9 A. I'm sitting here thinking. I 10 have never thought, it's never occurred to me as 11 a question. 12 Q. I guess maybe -- go ahead. 13 A. I'm not an eminently 14 recognized authority by my peers. 15 Q. All right. But you feel in 16 your own mind that you have some superior 17 knowledge of akathisia over and above that of the 18 ordinary psychiatrist? 19 A. Possibly. 20 Q. All right. Even though you've 21 never treated anyone for akathisia since you 22 graduated from your studies? 23 A. That's correct. 24 Q. Have you even seen a patient Page 129 1 who has complained of akathisia since you 2 graduated from your training? 3 A. No. 4 Q. Have you ever prescribed any 5 medication for an individual complaining of 6 akathisia since you completed your training? 7 A. No. 8 Q. Did you even see any patients 9 suffering from akathisia during your training? 10 A. Yes. 11 Q. Approximately how many? 12 A. Orders of magnitude, well over 13 multiple tens, and I suspect into the hundreds. 14 Q. Do you think you've seen as 15 many patients complaining of akathisia as Doctor 16 Worshing? 17 A. No. 18 Q. Not even close to those 19 numbers of patients seen by Doctor Worshing? 20 A. I wouldn't have a more 21 detailed estimate, he's seen more than me. 22 Q. Have you ever observed a 23 patient suffering of akathisia following the 24 administration of Prozac? Page 130 1 A. No. 2 Q. Never seen one in your 3 training or in any experience whatsoever? 4 A. No. 5 Q. Your knowledge concerning that 6 would be simply from reading observations of 7 others? 8 A. That's correct. 9 Q. Any other connections between 10 Prozac and adverse events that has a significant 11 association? 12 A. The prominent ones that come 13 to my mind, we have enumerated, nausea, headache, 14 sedation, asthenia, tiredness or fatigue, 15 anxiety, nervousness. 16 Q. Is it your testimony here 17 today, Doctor Beasley, that Prozac is a sedating 18 compound? 19 A. It's my testimony that a 20 minority of patients experience changes in one 21 direction or the other on psychomotor activity 22 status continuum that there is a statistically 23 significant association between Fluoxetine and 24 both psychomotor slowing and psychomotor Page 131 1 activation on the other side. It's been maybe 2 paradoxical, but those are the data. 3 Q. Do you -- are you telling us, 4 as a psychiatrist and a medical monitor of 5 Prozac, that Prozac makes people sleepy? 6 A. I'm saying -- you're implying 7 causality, and what I'm saying is that there's a 8 statistically significant association with 9 adverse events which reflect psychomotor slowing. 10 The two specific adverse events I have in mind 11 are somnolence and asthenia. 12 Q. Asthenia? 13 A. Yes, A-S-T-H-E-N-I-A. 14 Q. My question was, Doctor, does 15 Prozac make you sleepy? 16 A. One might presume that it does 17 since there is this statistically significant 18 association between these events. Again, this is 19 on a group basis, not necessarily in any 20 particular individual. 21 Q. Do you have knowledge of any 22 psychiatrist or general practitioners who are 23 prescribing Prozac for sleep? 24 A. You mean to induce -- Page 132 1 Q. Yes. 2 A. -- sleep? 3 Q. Yes. 4 A. No. 5 Q. Do you have an opinion 6 concerning whether or not Prozac is an agitating 7 medication -- I mean an activating medication? 8 A. Yes, I do. 9 Q. What is that opinion? 10 A. Again, in the majority of 11 patients, patients do not experience psychomotor 12 activation. Some percentage of patients do 13 experience this, and it is clear that it's 14 statistically significantly more than is seen 15 with placebo. It is manifested by -- again, I'm 16 basing this on adverse event reports. 17 Q. I don't mean to cut you off, 18 but did the clinical trial data support the 19 proposition that Prozac is activating? 20 MR. MYERS: Go ahead and finish your 21 answer, and then answer that question. 22 A. I was going to enumerate the 23 adverse events that I would include as 24 psychomotor activation. They include anxiety, Page 133 1 nervousness, insomnia, agitation, akathisia, 2 which has been very rarely reported as an adverse 3 event in the clinical trials, and then an adverse 4 event termed CNS stimulation. Now, to answer the 5 question, my opinion, the way that I would 6 characterize this compound, is as neither 7 activating nor sedating, but in a minority of 8 patients in fact demonstrating both phenomena. 9 Q. Well, hasn't it been 10 demonstrated in the clinical trials sponsored by 11 Lilly that Prozac is an activating medication? 12 A. You're drawing a conclusion, 13 your question to me is a conclusion. Again, I've 14 gone back and looked at those, the largest of 15 those trials and published data, and, I'm sorry, 16 but I would characterize it as somewhat 17 differently, more complex than you have in your 18 question to me. 19 Q. Is it your testimony here you 20 have never characterized the clinical trial data 21 as supporting the conclusion that Prozac is an 22 activating medication? 23 A. That is clearly one component 24 that it has for a minority of the patients. I Page 134 1 have characterized it in that fashion. 2 MR. SMITH: Let's break for lunch. 3 (A SHORT LUNCH RECESS WAS TAKEN.) 4 Q. (BY MR. SMITH) Doctor 5 Beasley, before we begin, when we ended for our 6 lunch break we were talking about adverse 7 reactions that in your opinion were caused by 8 Prozac by virtue of the fact that there was a 9 significant association statistically between 10 Prozac and the occurrence of the particular 11 events, correct? 12 A. I indicated that there were a 13 number of events that were statistically 14 significantly associated with Prozac, yes. 15 Q. Such as nausea, headache, 16 correct? 17 A. That's correct. 18 Q. Nervousness, agitation, and 19 anxiety to some extent? 20 A. Depending upon the clinical 21 trial data base, possibly, yes. 22 Q. You say depending upon the 23 clinical trial data base, what do you mean in 24 that respect? Page 135 1 A. With regard to some of the 2 events that you just mentioned that occurred and 3 reported less frequently, there might or might 4 not be a statistically significant occurrence 5 relative to placebo within an individual given 6 clinical trial. 7 Q. Are there more than one data 8 base that you're extrapolating this information 9 from? 10 A. There is a total data base 11 made up of controlled and uncontrolled clinical 12 trials, and there are of course individual trials 13 within that data base. So I'm referring to 14 looking at individual studies versus the totality 15 of the controlled clinical trial data base. 16 Q. Are you saying that for 17 instance you might see agitation in one 18 particular study, in one particular data base, 19 but if you looked at the data base as a whole, of 20 all studies, you wouldn't see agitation to the 21 statistical significance that you would in 22 looking at that one particular data base? 23 A. Actually I'm suggesting just 24 the opposite, that if you look at the totality of Page 136 1 the data base, there you tend to be -- if there's 2 a statistical association, you tend to be more 3 likely to see it in the totality of the data 4 base. That's not absolutely the case. You would 5 also be more likely to see it in larger studies 6 as opposed to smaller studies. 7 Q. So there's certain events or 8 occurrences that might not be picked up if you 9 looked at just a certain number of clinical 10 trials, but if you looked at all of the clinical 11 trials as a whole, you might find something like 12 agitation or anxiety that did appear? 13 A. Hypothetically, yes. 14 Q. With respect to anxiety and 15 agitation, that was what indeed occurred, was it 16 not? 17 A. Yes. 18 Q. So wouldn't it be important, 19 Doctor Beasley, to look at the entire data base 20 in making a determination with respect to whether 21 or not any particular finding presented a 22 significant association between Prozac and that 23 finding? 24 A. Could you help me understand Page 137 1 what we mean by data base? 2 Q. What you were using that's -- 3 A. Controlled. 4 Q. That is instead of looking at 5 a particular set of clinical trials, if you 6 looked at the entire spectrum of all the clinical 7 trials, you're more likely to pick up some 8 particular phenomena that's occurring as a result 9 of the drug as opposed to looking at one 10 particular trial or one particular group of 11 trials? 12 A. You would need -- to pick this 13 up, you would need trials that had some sort of, 14 again, control that we've been speaking of, the 15 statistical significant difference compared to 16 placebo. 17 Q. Did you find that in finding 18 that in looking at all trials as opposed to just 19 some trials, that you found with controls that 20 you found anxiety and agitation more frequently 21 or at a greater statistical significance than if 22 you just looked at the limited number of trials? 23 A. Okay. I have directed the 24 conduct of an analysis with regard to this issue, Page 138 1 actually combining several adverse event terms, 2 the ones that I described to you, in three 3 specific papers in three specific trials. So I 4 have looked specifically at three trials. I did 5 not conduct an analysis combining all of the 6 controlled clinical trials looking at this issue. 7 There is another publication in press which has 8 looked at the issue across all clinical trials, a 9 number of adverse event clusters, that was 10 primarily directed by Doctor Tollefson. In the 11 three trials that I looked at, two of those were 12 placebo controlled, and this cluster of adverse 13 events were statistically significantly -- 14 occurred statistically significantly greater than 15 with placebo. 16 Q. This analysis by Doctor 17 Tollefson that looks at all clinical trial data, 18 have you seen that? 19 A. Yes, I have. It was -- again, 20 this is the controlled clinical trial data base 21 where there's a comparator. It actually looked 22 at the issue of the relationship, temporal 23 relationship, between the emergence of activation 24 and suicidality. Page 139 1 Q. Okay. When was this study 2 done or when was this analysis made? 3 A. Okay. Because it was -- the 4 paper was -- I believe that the paper was 5 completed sometime last year or late in the 6 previous year. I say that because it has been 7 submitted for publication, sent, but it's not 8 appeared in press yet. 9 Q. Where has it been accepted for 10 publication? 11 A. Journal of Clinical 12 Psychopharmacology. 13 Q. Journal of Clinical -- 14 A. Journal of Clinical 15 Psychopharmacology. 16 Q. And what's the title of that 17 paper? 18 A. I don't recall the specific 19 title. 20 Q. Generally? 21 A. Fluoxetine Activation Sedation 22 and Lack of Association with Suicidality. It may 23 refer more generally to adverse events. 24 Q. Does the title of that paper Page 140 1 indicate the conclusion of the author? 2 A. Yes, it does, if I'm correct 3 about the title. 4 Q. Are you correct about the 5 conclusion? 6 A. Yes. 7 Q. And you say he looked at the 8 entire clinical trial, body of the clinical 9 trial? 10 A. Again, the control -- the U.S. 11 controlling clinical trial data base. 12 Q. Now, let's get clear on this, 13 Doctor Beasley. When you've got a publication, 14 an article, that looks at the U.S. control 15 clinical trial data base, that by a large stretch 16 of the imagination doesn't include all the 17 clinical trials done by Eli Lilly on the subject 18 of Prozac, does it? 19 A. No, that's the -- again, that 20 is the controlled, and I should specify as 21 opposed to depression clinical trial data base. 22 Q. Do you have any idea how many 23 clinical trials of any nature have been performed 24 by Eli Lilly with respect to Prozac? Page 141 1 A. Total number of trials? 2 Q. Yes, total number of trials. 3 Any indication under any protocol where Prozac, 4 Fluoxetine Hydrochloride, was administered to 5 such patients. 6 A. I don't know that number of 7 studies. 8 Q. You've been a medical monitor 9 on ten studies, correct? 10 A. I said approximately ten, yes. 11 Q. It's in the hundreds, isn't 12 it, Doctor Beasley, when you consider trials for 13 other indications, trials that are not 14 necessarily placebo controlled, trials done 15 outside the United States, trials where Prozac is 16 the comparator drug as opposed to the drug under 17 investigation? 18 A. That may well be the case. 19 Q. It wouldn't surprise you at 20 all if it was in excess of a hundred trials that 21 had been used? 22 A. No. 23 Q. How many trials did Doctor 24 Tollefson look at in his paper? Page 142 1 A. I don't recall the specific 2 number of those trials. 3 Q. Approximately? 4 A. I think it's fourteen or 5 seventeen. 6 Q. Fourteen or seventeen? 7 A. But again, that may not be an 8 absolutely correct answer. 9 Q. Out of a total of in excess of 10 a hundred clinical trials that had been run, 11 correct? 12 A. That's correct. 13 Q. In your meta-analysis, you 14 looked at only seventeen clinical trials? 15 A. That may be the correct 16 number, I don't recall precisely. 17 MR. SMITH: Get me a copy of of his 18 paper and we'll get the correct number right now. 19 (DISCUSSION OFF THE RECORD.) 20 (PLAINTIFFS' EXHIBIT NO. 1 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 Q. You recognize your Exhibit 1 24 as your meta-analysis, do you not? Page 143 1 A. I recognize this first page 2 that I'm looking at as the first page of the 3 report primarily authored by me on meta-analysis 4 within depression in the U.S. clinical trial data 5 base. 6 Q. Look under design there. 7 That's a retrospective analysis of pooled data 8 from seventeen double-blind clinical trials, 9 correct? 10 A. That's correct. 11 Q. So seventeen is the number of 12 trials that you looked at -- 13 A. That's correct. 14 Q. -- in your meta-analysis. And 15 at that time, in September of 1991, there were 16 also at least a hundred trials total in 17 connection with Prozac, weren't there? 18 MR. MYERS: You mean studies Lilly had 19 done? 20 MR. SMITH: Yes. 21 A. Again, I would not know the 22 specific number of studies. 23 Q. But you know it was in excess 24 of a hundred, don't you? Page 144 1 A. Again, I do not know the 2 specific number of studies. 3 Q. Did you look over the other 4 studies in making a selection of the seventeen in 5 which you were going to write on? 6 A. We selected all trials which 7 had a control arm and were double-blind as 8 described in the methods. 9 Q. I understand that. So you had 10 to make some analysis of all the trials to figure 11 out which one fit in the category you were 12 selecting, didn't you? 13 A. We had to look at the 14 description in the protocols of how the trials 15 were conducted. 16 Q. And it was in excess of a 17 hundred trials that had been run by the time this 18 article was published in September, '91, wasn't 19 there? 20 A. Again, I'm terribly sorry, but 21 your question implies an answer, and I'm 22 uncertain as to whether that answer is correct or 23 not. 24 Q. Would you be surprised that Page 145 1 there was in excess of a hundred trials? 2 A. No, I would not. 3 Q. Sounds reasonable, doesn't it? 4 A. I would not be surprised. 5 Q. So, is it your testimony that 6 you found some of the significant association 7 between Prozac, such as agitation and anxiety, by 8 looking at the total of the events reported in 9 the total of the clinical trials versus looking 10 at some limited clinical trial data? 11 MR. MYERS: I object to the form, 12 that's not what he said. Go ahead and answer. 13 A. Again, I can speak to my 14 analysis which looked at individual trials, okay, 15 and found this association. 16 Q. All right. You found the 17 association greater if you looked at the data for 18 all the clinical trials, didn't you? 19 A. Again, I don't know the answer 20 to that question. 21 Q. I thought that's where we got 22 to this point, because I originally asked you the 23 question, Doctor Beasley, you said depending on 24 what data base you look at, you may find Page 146 1 agitation or anxiety. 2 A. Right. 3 Q. I said what do you mean 4 depending on what data base you look at, and 5 didn't you say to me well, if you look at some of 6 the trials, you won't find it, but if you look at 7 the trial bases, all the trials as a whole, you 8 will find this as occurring. Is that wrong? 9 MR. MYERS: I object to the form. I 10 think the operative word was control, but I'll 11 let him answer that, I think that's where you've 12 gotten me. 13 MR. SMITH: I don't think I've gotten 14 you in any way. 15 MS. ZETTLER: I object, Larry, to you 16 suggesting an answer to the witness in your 17 objection. 18 MR. MYERS: I think it's in the 19 transcript. 20 A. What I recall is indicating to 21 you that hypothetically one would expect, if one 22 looked at a larger data base, be it across all 23 trials, a larger subset of trials as opposed to a 24 single trial, again I'm referring to controlled Page 147 1 trials where you can do a comparison, one would 2 hypothetically expect to see an effect if an 3 effect existed. What I mean by effect, a 4 statistical association. That's not an absolute 5 hard and fast rule that you're going to see it. 6 I then indicated that I had authored several 7 publications, two of which looked at placebo 8 Fluoxetine comparisons, and found statistically 9 significant association relative to placebo for 10 this set of events. I also indicated -- 11 Q. When you say set of events, 12 you mean activation, agitation? 13 A. The events were agitation, 14 insomnia, nervousness, anxiety, and then that a 15 further analysis has been conducted and has been 16 developed as a paper. I am one of the co-authors 17 on it, Doctor Tollefson is the senior author on 18 it, looking at this issue in the totality of the 19 data base. In addition to that, the association 20 not only with the activation, but the association 21 of activation or lack thereof with suicidality. 22 My recollection, again, having not been first 23 author on that, I am not absolutely certain, but 24 I believe, again, in that data base, analysis, Page 148 1 there would have been seen a statistically 2 significant increase in the rate of reported 3 activation with Fluoxetine re-relative to 4 placebo. 5 Q. So you're saying that both you 6 and Doctor Tollefson found the same thing in your 7 respective papers or analysis? 8 A. Again, I believe so. I'm more 9 familiar with the set of three papers, the two 10 relevant ones that I'm describing, compared to my 11 recollection of what's in both. 12 Q. So each of you found 13 activation and agitation in connection with 14 Prozac in the analysis of the clinical trials 15 that each of you did on separate occasions? 16 A. That's correct. 17 Q. All right. What accounts for 18 this, Doctor Beasley? 19 A. I'm at a loss to offer you any 20 acute biochemical or delayed biochemical 21 pharmacological explanation for this. 22 Q. Do you think that the source 23 is in a pharmacological biological explanation? 24 A. I don't know that it is or is Page 149 1 not. Again, what I have is a clinical finding, 2 reports by physicians, with regard to adverse 3 events, and the Fluoxetine treated patients 4 versus the placebo treated patients. That's the 5 data that I've got. 6 Q. What you're saying is that 7 agitation and activation occurs more frequently 8 among the Fluoxetine treated patients than it 9 does among the placebo treated patients? 10 A. Is reported more often, yes. 11 Q. And that that occurs to such 12 an extent that it's a statistical difference or 13 of statistical significance? 14 A. Reports of these events, yes. 15 Q. By virtue that you believe 16 that based on your analysis, that there are 17 individuals who truly do become more agitated and 18 more activated on Fluoxetine than on placebo? 19 A. There are more individuals who 20 report or are reported to experience these 21 phenomena. 22 Q. All right. And do you have 23 any doubt, then, that based on statistical 24 analysis, that Fluoxetine is causing or more Page 150 1 likely to cause agitation in some individuals? 2 A. My position is that the 3 statistical association exists. I don't know 4 what causes it. 5 Q. All right. Do you think the 6 answer may be in the fact that Fluoxetine has an 7 effect on serotonin and that serotonin plays some 8 role in this human response? 9 A. I don't know if it does or 10 doesn't. 11 Q. What about Fluoxetine is it 12 that's making these people more activated and 13 agitated? 14 A. Well, again, your question to 15 me -- you use the word making them, I'm presuming 16 that that's causal. 17 Q. Uh-huh. 18 A. What I have, again, is a 19 statistical association. I'm not certain what's 20 causing that. 21 Q. You're drawing an analogy, I 22 mean you're drawing a presumption based on that 23 statistical analysis, aren't you? 24 A. Yes. Page 151 1 Q. And you're saying because we 2 see this at a greater statistical significance, 3 then more likely in those individuals who are 4 reporting agitation and activation, it's by 5 virtue of the fact that they were given placebo -- 6 I mean given Fluoxetine, because it didn't occur 7 in those individuals who were not given 8 Fluoxetine as often? 9 THE WITNESS: Could you read the 10 question back, please? 11 (THE COURT REPORTER READ BACK THE 12 REQUESTED TESTIMONY.) 13 A. As often is quite important. 14 On an individual basis, it would be difficult to 15 say because you do see a substantial number of 16 patients on placebo reporting these events. 17 Clearly there's more, again, statistically 18 significantly more in association with 19 Fluoxetine. So on a group basis, one could 20 potentially infer that there is some relationship 21 between Fluoxetine and these events. 22 Q. So you can at least draw the 23 inference that there's a causal relationship in 24 those individuals, or causal link? Page 152 1 A. Again, that -- you have 2 statistical evidence suggesting that there is. 3 Q. To support a causal link? 4 A. But you don't know what that 5 causal link is, yes. 6 Q. My question is why do you see 7 this activation with Prozac more often than not? 8 A. And to that, again, I don't 9 have an answer. 10 Q. Wouldn't it have to be 11 something related to the Prozac and the fact that 12 Prozac affects brain chemistry, and specifically 13 affects serotonin, which has a specific influence 14 on conduct such as this? 15 A. And what I'm saying is my 16 belief is that I don't know what causes it. I 17 would clearly acknowledge that one could think 18 that, I mean you've asked me the question, but I 19 don't -- 20 Q. Is it a good question? 21 A. -- but I don't know what 22 causes this association between Prozac and these 23 events. I clearly know that they are there and 24 they're associated. Page 153 1 Q. Okay. And then do you know 2 what causes Prozac to relieve depression in some 3 individuals, anymore than you know what causes 4 Prozac to cause some individuals to become more 5 agitated or activated? 6 A. No. 7 Q. All right. But it's the claim 8 of Eli Lilly and Company that Prozac is an 9 effective efficacious antidepressant in a certain 10 portion of depressed individuals, is it not? 11 A. Absolutely. 12 Q. And do you believe that it's 13 efficacious yourself, sir -- 14 A. Absolutely. 15 Q. -- for that? So do you 16 believe that by virtue of the fact that Prozac is 17 relieving depression in some individuals is just 18 as likely to cause agitation and activation in 19 others? 20 A. Could -- I'm sorry, but could 21 you repeat the question? 22 Q. Sure. 23 MR. SMITH: Read it back. 24 (THE COURT REPORTER READ BACK THE Page 154 1 REQUESTED TESTIMONY.) 2 MR. MYERS: Let me object to the form 3 of the question because I think it may assume 4 that in the ones that don't get depressed, that 5 they become activated. I don't think that's what 6 he said, but go ahead and answer. 7 A. I would like to try to restate 8 back what I think the question was, which I 9 understood it to be because -- do I believe that 10 because Prozac relieves depression, it also 11 causes activation. 12 Q. In some individuals, not in 13 every individual. I mean we know Prozac doesn't 14 relieve depression in every individual, don't we -- 15 A. That's correct. 16 Q. -- who is depressed? 17 A. Right. 18 Q. And I'm not saying that Prozac 19 causes activation and agitation in every 20 individual who takes Prozac, I'm just saying it's 21 as likely that Prozac was the cause of the 22 agitation and activation in some individuals as 23 it was as likely that it was the cause of 24 relieving the depression in some individuals? Page 155 1 MR. MYERS: Same objection, go ahead. 2 A. Again, I don't know. I don't 3 think that because one happens, I believe that 4 the other happens, okay, not that because it 5 relieves depression, it also causes anxiety. I 6 clearly know activation -- I clearly know that 7 activation is associated with the compound. 8 Q. All right. And relief of the 9 depression is clearly associated with the 10 compound, is it not? 11 A. That's correct. But I'm not 12 sure that there's a causal link. 13 Q. You just wanted the good 14 effect, you don't want any potentially bad 15 effect, is that right, Doctor Beasley? 16 MR. MYERS: I object to the form, 17 that's not what he said, Paul, and you 18 misunderstand your own question. Mister Downey, 19 if you're going to be rude, go outside. 20 MR. DOWNEY: I don't believe my 21 laughter was rude, sir. 22 A. Again, I'm sorry, but I've 23 said that this activation that is present and 24 associated statistically significantly -- Page 156 1 Q. With Prozac? 2 A. -- with Prozac. 3 Q. Have you had any special 4 statistical training, Doctor Beasley? 5 A. I have had some elementary 6 statistical courses, I have not had extensive 7 training in statistics. 8 Q. When you say elementary 9 statistical courses, do you mean those courses 10 that one would ordinarily take in a college? 11 A. That's correct. 12 Q. What statistical courses did 13 you have at Yale? 14 A. I took psychology statistics, 15 a psychology statistics course. 16 Q. Any others? 17 A. There was a research design 18 course that was somewhat statistically related, 19 and then when I was in medical school, I had a 20 brief course. 21 Q. In statistics? 22 A. In statistics, a little mini 23 course. 24 Q. How long did that mini course Page 157 1 last? 2 A. I think it was about a week or 3 two. When I was in residency, as part of the 4 second year training program, there was a block 5 about statistics. 6 Q. But as far as any statistical 7 analysis that you made in connection with all 8 these papers that you've authored and things of 9 that nature, you employed statisticians for the 10 actual numbers crunching at Lilly, correct? 11 A. Statisticians decided upon the 12 analysis and performed those analyses. 13 Q. Did you have an opportunity to 14 call your office or to call Lilly and find out at 15 lunch how many individuals had attempted suicide 16 in this long-term efficacy study that you were 17 the medical monitor of? 18 MR. MYERS: Paul, I did. 19 MR. SMITH: All right. 20 MR. MYERS: The answer to the question 21 is as follows: The report has not yet been 22 submitted to the FDA. We'll produce the report 23 to you once it is submitted to the FDA, and I'm 24 trying to get information from Lilly to confirm Page 158 1 the total number of suicide attempts in the 2 study. I hope to be able to confirm that to you 3 if not this afternoon, then tomorrow, the total 4 number of attempts. 5 MR. SMITH: Well, regardless of 6 whether or not the study has been submitted to 7 the Food and Drug Administration, there's factual 8 information there that I need, that the witness 9 has testified about, concerning these attempted 10 suicides. Obviously we have a confidentiality 11 order in place, but I need to see it in order to 12 accurately examine the witness. 13 MR. MYERS: I'm not prepared to tell 14 you that I'm going to produce this report to you 15 before it's submitted to the Food and Drug 16 Administration, I'm not prepared to tell you that 17 today. I will certainly get you the information 18 on the number of suicide attempts. 19 MR. SMITH: See, I need that -- I 20 believe the witness testified that there was 21 factual recitations in the report concerning each 22 of the suicide attempts that he said he can't 23 give me information on unless he has the report, 24 and that this factual information is contained in Page 159 1 the report. 2 Q. Isn't that correct, Doctor 3 Beasley? 4 A. That's correct. 5 MR. MYERS: I understand what he told 6 you, and I understand exactly what you're saying. 7 MR. SMITH: So we're going to -- can 8 you give me an answer at either the end of the 9 day or beginning of tomorrow so I can know 10 whether or not it's going to be necessary for me 11 to file an appropriate motion? 12 MR. MYERS: Yes, I will, I'm just not 13 in a position to tell you today that I can give 14 you the report before it's submitted to the FDA. 15 I can give you the information on the total 16 number of suicide attempts. 17 MS. ZETTLER: When is the report 18 supposed to be submitted to the FDA? 19 MR. MYERS: I don't know the answer to 20 that. 21 MS. ZETTLER: Do you know, Doctor? 22 THE WITNESS: I don't think there's 23 any specified time requirement. 24 Q. (BY MR. SMITH) As I Page 160 1 understand it, it's at regulatory. 2 A. I have completed my portion of 3 this report. 4 Q. As I understand it, you don't 5 even have a copy of the report in your file, is 6 that correct? 7 A. No, that's correct. It's a 8 many volume report, I think, and I have not ever 9 seen the totality of the volumes with appendices 10 attached, it's probably fifty plus volumes. My 11 review of appropriate clinical sections has been 12 performed, and my understanding was that we 13 wanted to get it into -- from regulatory, through 14 that process into the FDA as expediciously as 15 possible. 16 Q. But you're finished with it as 17 far as you know? 18 A. Unless people would come back 19 to me with new questions that would be pertinent. 20 Q. But if somebody at regulatory 21 doesn't come back to you with new questions, as 22 far as you know it's going to go ahead and be 23 submitted -- 24 A. That's correct. Page 161 1 Q. -- to the Food and Drug 2 Administration? 3 A. That's correct. 4 Q. And that has a particular 5 section, I assume, on the suicides, suicide 6 attempts? 7 A. Well, there would be 8 particular sections that would be pertinent to 9 that, yes. 10 Q. And there are particular 11 sections that would describe the facts and 12 circumstance surrounding each of the attempted 13 suicides? 14 A. At least a substantial subset 15 of those, and would enumerate those in total. 16 Q. And there would be something 17 that would list the number of attempted suicides -- 18 A. That's correct. 19 Q. -- that occurred? 20 A. That's correct. 21 Q. All right. When you started 22 in July, 1987 until July, 1989, you were 23 associate clinical research physician, correct? 24 A. That's correct. Page 162 1 Q. And at that time you were 2 working on Prozac sixty to seventy percent of the 3 time, approximately, is that right? 4 A. That's correct. 5 Q. Teicher's article didn't come 6 out until February, 1990, and you were aware of 7 it in January of 1990, correct? 8 A. Just before its publication. 9 Q. Is that right? 10 A. That's correct. 11 Q. And did you do any work in an 12 analysis of the issue of whether or not suicide 13 and Prozac were linked prior -- while you were an 14 associate clinical research physician up to July, 15 1989? 16 A. I clearly went back and looked 17 at the Wernicke data at some point, became aware 18 of that and looked at it. 19 Q. Why did you look at that? 20 A. Okay. As I recall, there was 21 a conversation that I had at an APA meeting, and 22 again, I believe it was the APA, it was the APA 23 in San Francisco, I forget which specific year 24 this was, I believe it was the -- I believe it Page 163 1 was the 1989 APA. So again, this would have been 2 after I had been promoted from associate to 3 clinical research physician, if I'm recalling the 4 temporal sequence correctly, in which a Doctor 5 Norden had reported to me that he had seen a 6 patient who he believed in his clinical practice 7 may have had increasing suicidality, and I 8 believe that he reported that another physician 9 may have had emergent suicidality that was of a 10 pressing nature, and this clearly stimulated a 11 look back for information that might be relevant 12 to suicidality. I brought this to the attention 13 of my management, and although I can't recall 14 specifically, we think that at least in the 15 enumeration of the controlled data bases to look 16 at counts of suicidality in the data base. 17 Q. All right. Who is this Doctor 18 Norden? 19 A. Doctor Norden was an 20 individual, I believe, from Washington. I 21 actually knew of him secondarily because he had 22 filed a use patent for Prozac for virtually every 23 potential psychiatric indication known to man, a 24 very lengthy list of potential indications for Page 164 1 the compound. 2 Q. What is his first name? 3 A. I don't recall his first name. 4 Q. So he just comes up to you at 5 an APA meeting and said look, I've seen a patient 6 with increasing suicidality and I know of another 7 physician who has had a patient with increasing 8 suicidality that was of a pressing nature, is 9 that correct? 10 A. I'm not sure he described his 11 patient as having suicidality of a particular 12 pressing nature. 13 Q. But the other patient did? 14 A. Actually, I think it was 15 several other patients on the part of this one 16 physician. 17 Q. Several other patients than 18 what? 19 A. Several other patients of this 20 other physician. 21 Q. As well as this physician, 22 Doctor Norden, had seen it also in some of his 23 patients? 24 A. Again, I believe that Doctor Page 165 1 Norden reported to me a single patient with some 2 worsening of suicidality, suicidal ideation. I 3 don't recall him characterizing it in any 4 specific way. 5 Q. How did he single you out as 6 an individual to bring this to, had you presented 7 a paper on Prozac or did you have Lilly 8 paraphernalia on you or something of that nature? 9 A. I was in fact sitting at the 10 Lilly exhibit at the APA. I don't think Doctor 11 Norden knew me, he was probably directed to me as 12 a physician working with Prozac. 13 Q. Okay. And then you -- that 14 was the first time it had been raised in your 15 mind? 16 A. The other patient that I told 17 you about -- the other report that I told you 18 about that Doctor Heiligenstein took, I don't 19 know which of these occurred and which of these 20 was first. 21 Q. All right. 22 A. I believe very clearly that 23 they were both prior to Doctor Teicher's article. 24 Q. All right. But you do know Page 166 1 that they were both prior to the Teicher article? 2 A. I'm quite certain. 3 Q. To a more reasonable degree of 4 certainty? 5 A. Yes. 6 Q. Other than that, you never 7 heard the issue raised that Prozac could be 8 related to suicidality? 9 A. I can't recall any. 10 (PLAINTIFFS' EXHIBIT NO. 2 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Take a minute to look at that 14 document marked as Exhibit 2. Have you ever seen 15 Exhibit 2 before? 16 A. I cannot recall having seen 17 Exhibit 2, no. 18 Q. Obviously the date of this 19 document is April 3, 1985, correct -- or April 20 2nd? 21 MR. MYERS: Right there. 22 A. Yes. I'm a bit confused, and 23 it looks to me like it's -- I'm sorry to say 24 this, something has been cut off because just Page 167 1 below that I see a date of April 29th, and April 2 30th, 1985, and the date above is an earlier date 3 with a line through it. 4 Q. Right, but then up on the top 5 left-hand corner, there's a fax or telex 6 indentation showing April 3rd. Lilly, Bad 7 Homburg, right? 8 A. That's correct. May I comment 9 on what it looks like to me? It looks like the 10 top part was a half sheet that was on top of 11 something else when it was xeroxed if this date 12 below is correct, because it's a later date. 13 Q. Oh, you're saying you think 14 that possibly this To, CCs, From and Date doesn't 15 really go with where it says report on Fluoxetine 16 working section? 17 A. Well, I'm sorry, but what -- 18 the date that's below the line that seems to go 19 with the rest of this is a date later, April 29th 20 and 30th, 1985. That's after April 3 or April 21 2nd, April 3rd, 1985. 22 Q. Uh-huh. 23 A. So I'm wondering how you could 24 fax and date something and send it prior to the Page 168 1 date associated with the document. 2 Q. I agree. This is just the way 3 we got the document, from Lilly. 4 A. I just pointed out -- 5 Q. It was in Doctor Zerbe's file. 6 A. You asked me to comment on the 7 date. 8 Q. It may have been -- I don't 9 know what would have been on the bottom of the 10 top page or the top of the bottom page other than 11 what's been shown to me here, Doctor Beasley. 12 A. Okay. I'm -- there's a 13 transmittal page with names on it early April, 14 and then there's a report from late April, and 15 that's what we're looking at. 16 Q. And there's sort of a line 17 there also, isn't there, between the two? 18 A. That's correct. 19 Q. Which indicates that maybe 20 there was a short piece of paper on the top 21 stapled to something that has been covered up by 22 this short piece of paper, and that it's been 23 copied, doesn't it? 24 A. I don't know. As I said, Page 169 1 there's a line on the paper, and from my 2 perspective, there is internal inconsistency 3 between the date on what looks like an addressee 4 list and what's below. 5 Q. All right. Well, I'll 6 represent to you, Doctor Beasley, this is just a 7 condition in which we received the document. 8 Well, have you ever seen this, regardless of the 9 date of the document? 10 A. I cannot recall ever seeing 11 this, no. 12 Q. Do you think this would be 13 something that you would recall seeing? 14 A. I think so. 15 Q. By virtue of your work on 16 Prozac and suicidality? 17 A. If I had seen it, I believe I 18 would recall this. 19 Q. Yes. It looks like that 20 apparently Lilly's affiliate in Germany has 21 called in an expert or professor to give them 22 advice on the best way to register Fluoxetine in 23 Germany, does it not? 24 MR. MYERS: Before he starts Page 170 1 answering, let me just make an objection to the 2 whole line of questioning about -- this thing is 3 dated April of '85, he didn't go to work for 4 Lilly until July of 1987, and I think it's 5 improper to examine him about things that he 6 wasn't even here for. 7 MS. ZETTLER: He already said he 8 reviewed the Wernicke information related to the 9 issue, Larry. 10 MR. MYERS: He didn't say he reviewed 11 this. 12 MS. ZETTLER: The Wernicke information 13 is related to this issue, the German issue. 14 MR. MYERS: Go ahead and answer, but I 15 object to the whole line of questioning. 16 MR. SMITH: I suspect that you would. 17 MR. MYERS: I think it's an utter 18 waste of time to examine the man about something 19 he was not even here for. 20 Q. Let's get this clear, Doctor 21 Beasley. When you wrote your paper on Prozac and 22 suicide and presence or absence of suicidal 23 ideation, you attempted to make a scholarly 24 approach to that paper, did you not? Page 171 1 A. That's correct. 2 Q. And you attempted to make 3 yourself familiar with the state of the knowledge 4 concerning Prozac and its relation to 5 suicidality, did you not? 6 A. Endeavored to understand the 7 nature of the U.S. depression clinical trial data 8 base, and as thoroughly as possible -- 9 MR. MYERS: Go ahead and finish. 10 A. -- as it existed at the time 11 the analysis was conducted. 12 Q. And the analysis that you 13 conducted was in 1990, correct? 14 A. That's correct. 15 Q. But it reviewed clinical 16 trials that had been done early on, did it not? 17 A. It included all of the 18 double-blind clinical trials -- 19 Q. All right. 20 A. -- placebo or tricyclic that 21 were conducted in the U.S. within depression. 22 Q. Back to the beginning of time 23 within which they were done? 24 A. That's correct. Page 172 1 Q. Even though you had just been 2 with -- you started with Lilly in 1987, you 3 reviewed the information that Lilly had and that 4 was written prior to your getting there, didn't 5 you, when you compiled this paper? 6 A. We used all of the available 7 clinical trial report information to develop this 8 paper, yes. 9 Q. Look at Exhibit 2, Doctor 10 Beasley, under data reviewed. It's on the front 11 page. 12 A. Yes. 13 Q. The data reviewed there was 14 original documentation submitted March 1, 1984, 15 wasn't it? 16 A. Original documentation 17 submitted March 1, 1984, that's correct. 18 Q. Do you know what that would 19 be? 20 A. No. 21 Q. Number two is an analysis of 22 pooled studies, Fluoxetine versus Imiprimine 23 versus placebo, protocol number twenty-seven 24 submitted October 26, 1984. You know full well Page 173 1 what that is, don't you, Doctor Beasley? 2 A. I'm terribly sorry, but I 3 don't know specifically which protocol number 4 twenty-seven is. I have a good idea which one it 5 is because there's only one clinical trial in the 6 data base which was Fluoxetine, Imiprimine, 7 placebo, as far as I know. 8 Q. And it was the subject of data 9 that you used in your paper, wasn't it, Doctor 10 Beasley? 11 A. Yes, it was. 12 Q. All right. This paper 13 indicates that professor -- we can look on the 14 back page. Professor Herrmann left an opinion of 15 twenty-one typewritten pages, doesn't it? 16 MR. MYERS: Tell him where you are 17 reading from so he can look at it. 18 MR. SMITH: Page one. 19 A. Yes. 20 Q. And then this document 21 indicates that it's a summary of his opinion, is 22 it not, does it not? 23 A. Yes, the last statement 24 indicates that this is a summary. Page 174 1 Q. Turn with me to page two where 2 it says safety. Look under bullett point one, 3 two, three, four, five, six, seven. Do you see 4 that? 5 A. Yes, I do. 6 Q. Still not resolved is the fact 7 that suicide attempts have been observed more 8 frequently on Fluoxetine as it compared to 9 Imiprimine, paren, only epidemiological data or 10 literature of other antidepressants may help to 11 identify whether it happened by chance, that 12 incidence of suicide attempts was abnormally high 13 on Fluoxetine or abnormally low under 14 comparitors, close paren, end quote, correct? 15 A. That's correct. 16 Q. Protocol number twenty-seven 17 is the comparison of Fluoxetine and Imiprimine, 18 is it not? 19 A. From reading the first page, 20 that would have also involved placebo. 21 Q. Yes. And that's the subject 22 of your -- forms part of the data that's 23 contained in your paper? 24 A. I believe it's one of the Page 175 1 seventeen studies. 2 Q. All right. Apparently this 3 expert is opining that suicide attempts have been 4 observed more frequently on Fluoxetine as 5 compared to Imiprimine, correct? 6 A. Whoever summarized his views, 7 I would understand that to be their belief from 8 the summary. 9 Q. Have you read the twenty-one 10 page report that this expert hired by Lilly made? 11 A. No, I have not. 12 Q. And you had never read this? 13 A. No. 14 Q. Prior to beginning your work 15 on your analysis of whether or not Prozac was 16 associated with suicide? 17 A. Again, I do not recall reading 18 this. 19 Q. You would remember it had you 20 read this, don't you think, Doctor? 21 A. I believe that I would have. 22 Q. Because frankly, you were not 23 aware that anyone at the time you wrote your 24 meta-analysis had observed that suicide attempts Page 176 1 have been observed more frequently on Fluoxetine 2 as compared to Imiprimine, correct? 3 MR. MYERS: In that study? 4 MR. SMITH: Yes. 5 A. I was not aware of, again, 6 this report. Within the paper, the rate of 7 suicides, suicide attempts, is relatively low. 8 In some of those, I don't recall specifically, 9 there may have been numerically more than with 10 Imiprimine or with placebo. 11 Q. But the paper doesn't say 12 numerically more, this Exhibit 2 says suicide 13 attempts have been observed more frequently on 14 Fluoxetine as compared to Imiprimine. 15 A. Again, from reading the 16 summary, I'm not sure what that means, I don't 17 have the data that this report was based on in 18 front of me. I would read that to mean, and 19 again, I would be inferring, numerically more. 20 It clearly does not say statistically 21 significantly more. What I'm meaning to is that 22 given this summary, I don't know much more, I 23 don't know anything more than what it says right 24 here, observed more frequently. Page 177 1 Q. Obviously the twenty-one page, 2 a reading of the twenty-one page typewritten 3 report might be of more value. 4 A. Might contain more data to 5 explain what was meant by the summary. 6 Q. Would you find that useful to 7 see that paper? 8 A. Useful in what? 9 Q. In understanding what the 10 meaning of this statement is here? 11 A. Potentially, yes. 12 Q. Because obviously the 13 conclusion this author is under benefit risk 14 ratio, that it's not unequivocally positive, and 15 it's therefore of great importance to determine 16 certain types of patients who will better respond 17 to Fluoxetine than to Imiprimine so that higher 18 risk might be acceptable, correct? 19 A. That is in fact the summary 20 statement with regard to the benefit risk ratio. 21 Q. If you were to attempt to find 22 this twenty-one page report within the Lilly 23 organization, where would you look, Doctor 24 Beasley? Page 178 1 A. I would query the regulatory 2 people, I would query individuals who were -- 3 assuming this is who received this report, these 4 individuals. I would query the German office in 5 an attempt to discover its possible presence, and 6 I would want to know who the individual was who 7 in fact signed their name here, Doctor Johanna 8 Schenk. 9 Q. You don't know who she is? 10 A. No. 11 Q. Do you know of an authority in 12 the field in Germany by the name of Herrmann, 13 spelled H-E-R-R-M-A-N-N? 14 MR. MYERS: An authority in the field -- 15 oh, in the field of psychiatry, I'm sorry. 16 A. I'm not familiar with that 17 name. 18 Q. Never seen any scientific 19 articles or any data published by Doctor 20 Herrmann? 21 A. Not that I recall. 22 Q. Would you like a break, 23 Doctor? 24 A. I would love one. Page 179 1 (A SHORT RECESS WAS TAKEN.) 2 Q. Doctor Beasley, in connection 3 with the Tollefson article that has apparently 4 been submitted for publication -- 5 A. The one that we were speaking 6 about earlier? 7 Q. Yes. 8 A. Yes. 9 Q. Did it analyze the same pool 10 of clinical trial participants that your paper 11 did? 12 A. I believe that it did. It 13 might have included an additional completed 14 study. 15 Q. All right. And which study 16 would that have been? 17 A. Again, I'm not certain. There 18 may have been a Nortriptyline comparison, 19 Fluoxetine, Nortriptyline comparison study that 20 might have been completed and included in that 21 analysis. 22 Q. And you say you were a listed 23 author of the Tollefson article also? 24 A. That's correct. Page 180 1 Q. And do you have that article 2 in your file? 3 A. Yes, that would be -- hold it, 4 let me think about that. Actually, I'm not sure 5 whether that would exist in my files or not. 6 Q. When did you begin work on 7 your meta-analysis? 8 A. It was, I would say, shortly 9 after receiving Doctor Teicher's report. 10 Q. So early 1990? 11 A. That's correct. 12 Q. And I believe it was published 13 in the September, 1991 issue of the British 14 Medical Journal, correct? 15 A. I believe that's correct. 16 Q. And you reviewed seventeen 17 trials in your meta-analysis that had been 18 completed up to the end of December, 1989? 19 MR. MYERS: Will you reference a page. 20 A. It clearly indicates seventeen 21 single-center and multi-center randomized 22 double-blind trials, I can't find immediately the 23 date for those trials. 24 Q. Look under methods on page Page 181 1 two, types and sources of data, quote, trials 2 that had been completed and analyzed up to the 3 end of December, 1989. 4 MS. ZETTLER: You said '99? 5 MR. SMITH: '89 is what I said. 6 Q. Correct? 7 A. Yes, 1989, that's correct. 8 Q. Did someone give you the 9 assignment to prepare the meta-analysis? 10 A. Doctor Masica assigned me to 11 work on the issue. I would not characterize 12 myself as the preparer. Many people worked on 13 the effort. I would characterize myself as the 14 final coordinator and author, organizer. 15 Q. Would it be accurate to 16 characterize you as being the individual 17 responsible for collecting the data, selecting 18 the data, and being the primary author on the 19 paper? 20 A. Actually, with regard to the 21 second issue, which was selecting the data, I 22 would characterize the statisticians as having 23 substantial, if not the primary, input into that. 24 I of course had responsibility for the clinical Page 182 1 aspects of the work, but determining that a trial 2 should or should not be included in the criteria 3 for that, the double-blindedness, the controlled 4 nature of the trial, was a statistical issue. 5 Q. But as the final author of the 6 paper, and as a M.D. psychiatrist, you would have 7 the ultimate responsibility for selecting the 8 trials that would be used? 9 A. Again, I viewed that as a 10 collaborative decision to once the decision had 11 been made to include placebo and tricyclic 12 comparator trials that were well controlled. I 13 collaborated in that decision, and I would have 14 been the individual who would have reviewed 15 protocols to make certain that they met those 16 criteria, although they were -- the studies that 17 met those criteria were fairly easily 18 recognizable. 19 Q. But the final analysis was 20 yours, was it not? 21 A. Again, I did not perform the 22 statistical work, I wrote the introduction, the 23 conclusion, and reviewed the entire paper. 24 Q. Well, now, are you going to Page 183 1 tell us that there's some part of this paper that 2 you don't take responsibility for, Doctor 3 Beasley? 4 A. Oh, I take responsibility for 5 this paper. 6 Q. Okay. Let's talk about -- 7 A. But my -- go ahead. 8 Q. Let's talk about your analysis 9 of suicidality that occurred during the clinical 10 trials, all right? 11 A. Yes. 12 Q. You made an analysis, it took 13 you some period of time to do the analysis, 14 correct? 15 A. That's correct. 16 Q. There had to be some planning 17 as to what data you would select and how you 18 would accumulate that data? 19 A. That's correct. 20 Q. There had to be some plan with 21 respect to how it would be presented in a paper, 22 correct? 23 A. That's correct. 24 Q. And this took a number of Page 184 1 months, I would assume? 2 A. That's correct. 3 Q. How many months would you say? 4 A. I don't recall the time of the 5 first submission of the the paper for 6 publication. As I said, the work began shortly 7 after receiving Doctor Teicher's communication. 8 Q. But the assignment was to 9 review, I would assume, the clinical trial data 10 to see if there was any evidence of Teicher's 11 assertions, is that right? 12 A. That's correct. 13 Q. And with a view toward 14 publishing the results of your analysis. 15 A. Not necessarily, that was not 16 articulated at the time. 17 Q. You didn't know at the outset, 18 when you began the study, that you were going to 19 end up publishing? 20 A. Not necessarily, no. 21 Q. Did you think if the analysis 22 was something that was favorable, it would be 23 published? 24 A. No, there was no expression Page 185 1 one way or the other. I think the primary issue 2 was one of both investigating a significant 3 public health issue, and of course conveying 4 findings to regulatory agencies. 5 Q. Was there anything you found 6 in your analysis that was conveyed to the 7 regulatory authorities? 8 A. There were regulatory reports 9 that were in fact conveyed specifically to the 10 FDA, I'm uncertain about what other international 11 regulatory bodies they would have been conveyed 12 to. These were very large detailed reports of 13 which this is a shortened version. 14 Q. And you say you did submit all 15 the underlying data in your compilations that you 16 made to the FDA? 17 A. When you refer to underlying 18 data, I'm not exactly sure what you have in mind. 19 Clearly the case report forms and the electronic 20 media formed the basis for the data that we 21 collected, and this had been previously 22 submitted. This was not resubmitted to the FDA. 23 Q. But was your analysis of that 24 data submitted to the FDA? Page 186 1 A. Yes. 2 Q. Why, since they already had 3 it? 4 A. They did not have the 5 analysis. 6 Q. Okay. Whose decision was it 7 to submit that analysis to the FDA? 8 A. I'm not sure who made that 9 explicit decision, I don't know who made that 10 explicit decision. 11 Q. Well, do you see any reason 12 that would justify your submitting your analysis 13 to the FDA and not submitting the twenty-one page 14 report written by the consultants for the German 15 regulatory authorities to the FDA? 16 MR. MYERS: I object to the form. 17 A. I wouldn't feel that the 18 German report should not be submitted. It may 19 well be that it could have been submitted, I 20 don't know. 21 Q. Well, I guess the reason I 22 asked is that we asked Mister Wood, who was 23 chairman of the board of Lilly at the time, last 24 week, whether he would have submitted this Page 187 1 twenty-one page report, and he said he would not 2 have. But you see no distinction in submitting 3 your report and the twenty-one page German 4 report? 5 MR. MYERS: Before he answers, let me 6 object to the form because I don't think you 7 precisely characterized Mister Wood's testimony. 8 MR. SMITH: You're amazing. 9 MR. MYERS: I don't think you have. 10 A. Having not seen the report, I 11 don't know whether I would or would not have 12 submitted the report to the Germans to the FDA. 13 Q. All right. Now, your analysis 14 said that you reviewed seventeen double-blind 15 clinical trials, correct? 16 A. That's correct. 17 Q. When in fact there had been 18 over a hundred clinical trials done by Lilly at 19 that time. 20 A. I'm sorry, but again, I'm 21 unaware of the specific number. You've asked me 22 in the past would I be surprised if that was the 23 number, and I said I would not be surprised. 24 Q. The seventeen trials that you Page 188 1 analyzed for the basis of your paper, for the 2 basis of your opinion, is just a minority of the 3 clinical trials that were done by Lilly using 4 Prozac, weren't they? 5 A. You're talking about trials 6 over all indications or just within depression? 7 Q. Over all indications. 8 A. Okay. This analysis 9 represents a minority, but there were additional 10 analyses done of the controlled data bases for 11 other large indications as well. Whether or not 12 with all of the analyses that were done in the 13 different indications, including bulimia, 14 obesity, and obsessive-compulsive disorder, it 15 would again be speculative for me to make a 16 statement as to whether or not that represented a 17 majority or minority of patients treated. 18 Q. I don't understand. 19 A. Okay. 20 Q. Can you clarify that? 21 A. Yes. You asked me -- what I 22 think you asked me is were the analyses 23 completed, and you referred to specifically this 24 paper, did this represent a minority of patients, Page 189 1 in total, treated with Fluoxetine? 2 Q. Yes. 3 A. I'm virtually certain that 4 that's the case. What I had added was that there 5 were analyses done in other indications as well. 6 Q. But they're not included in 7 this paper, are they? 8 A. No, they're not included in 9 this paper. 10 Q. I'm talking about this 11 analysis for this paper. 12 A. That's right. 13 Q. And the fact is is the 14 analysis that you made is an analysis of a 15 minority of the patients who had been involved in 16 clinical trials on Prozac. 17 A. That's correct. 18 Q. And is a minority of the 19 number of clinical trials done using Prozac by 20 Lilly? 21 A. I would not be -- again, I 22 would not be surprised if that was the case. 23 Q. Clinical trials that are 24 analyzed are only United States clinical trials, Page 190 1 aren't they? 2 A. That's correct. 3 Q. There was no analysis made of 4 the outside United States clinical trials that 5 were in existence at the time in this paper? 6 A. In this paper, no. 7 Q. There were double-blind 8 clinical trials using Fluoxetine for depression, 9 controlled against placebo or tricyclic 10 antidepressants, done outside the United States 11 that weren't included in this analysis, weren't 12 there? 13 A. Yes. 14 Q. You only -- in other words you 15 limited to -- you limited the analysis to 16 double-blind randomized trials of Fluoxetine in 17 depression controlled against placebo or 18 tricyclic antidepressant in the United States? 19 A. In this report, that's 20 correct. 21 Q. Even though there were exactly 22 studies comparing these substances in the same 23 manner being done outside the United States? 24 A. In this report, that's Page 191 1 correct. 2 Q. It's true, isn't it, in fact, 3 Doctor Beasley, that the clinical trials were not 4 meant to assess suicidality, were they? 5 A. No, they were intended to 6 assess the efficacy and overall safety of 7 Fluoxetine. A component of that would be 8 suicidality, but they did not have that as the 9 specific goal. 10 Q. So the answer to my question 11 of the goal of the clinical trials analyzed was 12 not to analyze suicidality would be yes, wouldn't 13 it, Doctor? 14 A. You're correct, yes. 15 Q. The only measure of 16 suicidality in the clinical trials was the 17 Hamilton depression scale, was it not? 18 A. Along with adverse event 19 reports. 20 Q. All right. But the only scale 21 used in the clinical trials to assess suicidality 22 was the Hamilton depression scale? 23 A. That's correct. 24 Q. And the only part of that Page 192 1 Hamilton depression scale that focuses in any way 2 on suicidality is item three, is it not? 3 A. That's correct. 4 Q. Item three is simply a zero to 5 four analysis of suicidal ideation and acts, is 6 it not? 7 A. That's correct. 8 Q. It is one seventeenth or one 9 twenty-second of the total Ham-D scale, isn't it? 10 A. There are a number of versions 11 of the Hamilton scale, but -- 12 Q. That's why I used one 13 seventeenth or one twenty-second. 14 A. One twenty-first. 15 Q. Twenty-first. You will agree 16 with me that the suicidality portion of the 17 Hamilton depression scale comprises only either 18 one seventeenth or one twenty-first of that 19 scale. 20 A. That's correct. 21 Q. And the scale itself, the 22 Ham-D item three, is only a measurement from zero 23 to four, is it not? 24 A. That's correct. Page 193 1 Q. There are other scales that 2 measure suicidality with more certainty, are 3 there not? 4 A. I would not submit -- not 5 agree with you that they measure it with more 6 certainty, the word that you used. 7 Q. Accuracy? 8 A. All right. No, not accuracy. 9 Q. Do you know what the Beck 10 Suicide Inventory is? 11 A. Yes, I do. 12 Q. That wasn't a bit used in any 13 of these clinical trials that you analyzed, was 14 it? 15 A. No, it was not. 16 Q. The Beck Suicidal Inventory 17 Scale is much more sophisticated in determining 18 suicidal ideation, isn't it, Doctor Beasley? 19 A. I would say certainly 20 characterize it as more sensitive. 21 Q. Okay. 22 A. It's interesting that Beck 23 actually validated his scale using a very similar 24 item to the Hamilton from his overall depression Page 194 1 rating scale. 2 Q. Doctor Beasley, if you were 3 concerned about relatives of yours and whether or 4 not they had emergent suicidality as part of 5 their depression, would you rather they be given 6 the Ham-D item three analysis by a competent 7 investigator or would you rather them be given 8 the Beck Suicide Inventory? 9 A. Actually, I wouldn't be 10 particularly concerned about the use of a scale. 11 I mean if you're talking about an individual, a 12 person, one of my relatives, who a clinician has 13 reasonable feeling on basically a scale of zero 14 one, thinks they're becoming suicidal or having 15 substantial increase in their suicidality, I 16 would want them to take appropriate clinical 17 action. 18 Q. Which would be what? 19 A. Be a variety of things. 20 Potentially hospitalization, whatever the 21 clinician deemed to be appropriate under the 22 given circumstances. 23 Q. If you had a relative who was 24 becoming suicidal, would you have any objection Page 195 1 to that relative receiving Prozac? 2 A. No. 3 Q. The scale used in the clinical 4 trial, the Hamilton item three portion of the 5 depression scale -- 6 A. Uh-huh. 7 Q. -- is much less sensitive to 8 detect degrees and extents of suicidal ideation 9 than the Beck Suicide Inventory, isn't it? 10 A. I indicated that in my opinion 11 it was less sensitive, meaning that it would not 12 pick up, relatively speaking, small changes as -- 13 the Hamilton would not pick up small changes as 14 well as the Beck would. 15 Q. How about the Adult Suicide 16 Ideation Questionnaire, isn't that much more 17 sensitive in picking up changes in suicidality 18 than the Ham-D-3 used in all of the clinical 19 trials that were under analysis in your paper? 20 A. Doctor Reynolds' scale is a -- 21 which is the scale that you're referring to, is a 22 self-rating scale. There are some -- there's 23 debate in the psychiatric literature about the 24 validity of self ratings versus clinician Page 196 1 ratings. My personal opinion is, again, that the 2 validity issue aside, it would be more likely to 3 be more sensitive to small changes in amount of 4 suicidal ideation. Again, the Ham-D item three 5 was used by Doctor Reynolds to validate his 6 scale. 7 Q. Are you telling us, Doctor 8 Beasley, that you think the Ham-D item three was 9 adequate to measure the suicidality in 10 individuals participating in the clinical trials 11 of Prozac for depression? 12 A. I'm telling you it's an item 13 with significant scientific support. I'm telling 14 you that in my personal opinion, it's sufficient 15 to detect large changes in suicidal ideation. 16 I'm also telling you that I believe it's less 17 sensitive than the other instruments that you've 18 mentioned to detect relatively smaller changes in 19 suicidal ideation. 20 Q. Do you have any reason to know 21 why the FDA was requesting that Lilly use a more 22 sensitive instrument to measure suicidality in 23 trials that started after this controversy arose? 24 A. Again, I'm not certain why the Page 197 1 individuals at the FDA made the request. 2 Q. You were present at meetings 3 when they made that request, weren't you, Doctor 4 Beasley? 5 A. Yes, I was. 6 Q. And you heard them express the 7 reasons for their request, didn't you? 8 A. I don't recall those specific 9 reasons. I have acknowledged that it's more 10 sensitive, and I would believe that they wanted a 11 more sensitive instrument. 12 Q. Did you want a more sensitive 13 instrument? 14 A. I believe that it would be 15 reasonable to include a more sensitive instrument 16 in further clinical trials. 17 Q. Why weren't you using this 18 more sensitive instrument in the latest clinical 19 trials that you were the medical monitor of, this 20 long-term efficacy study? 21 A. I believe that trial began 22 being developed and the protocol was agreed to 23 before this became a significant issue. 24 Q. So you didn't use it because Page 198 1 the FDA didn't require it. 2 A. No. I believe that it was not 3 used because the trial was developed prior to 4 increasing levels of concern about suicidality. 5 Q. Well, the trial certainly 6 wasn't completed until long after this issue 7 arose. 8 A. That's correct. 9 Q. There wouldn't have been 10 anything that would have prevented you from 11 adding this to the clinical trial process, would 12 there? 13 A. It would have been introduced 14 after a number of patients would have already 15 completed the trials, presumably those with 16 suicidal ideation who had left early. So in that 17 sense, there would be issues with regard to the 18 scientific validity because you only have part of 19 your sample. 20 Q. Are you telling me that in 21 that long-term efficacy trial there were 22 individuals who developed suicidal ideation and 23 were discontinued from the trial? 24 A. I've already indicated to you Page 199 1 that there were several suicidal attempts. Those 2 patients obviously had increasing suicidal 3 ideation and were discontinued from the trial. 4 Q. But I take it that there may 5 have been earlier than these five attempts that 6 people developed suicidal ideation and were 7 discontinued from the trial by virtue of the 8 answer you gave a minute ago? 9 A. I was thinking specifically of 10 these patients who committed attempted suicide. 11 Q. All right. Then think of 12 specifically the individuals that developed 13 suicidal ideation during that trial, were there 14 individuals who developed suicidal ideation other 15 than the suicide attempted that were discontinued 16 early from that trial? 17 A. I would need to look at the 18 clinical trial report and the reasons for 19 discontinuation to determine that. 20 Q. Well, what is your 21 recollection concerning that, Doctor Beasley? 22 A. I don't recall any, but that's 23 not to say that they don't exist. 24 (PLAINTIFFS' EXHIBIT NO. 3 WAS Page 200 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 Q. Look at Exhibit 3, Doctor 4 Beasley. Apparently you were copied in on that? 5 A. Uh-huh. 6 Q. And I think we can probably 7 save a little time, and you certainly are welcome 8 to read the entire memo. Look at page two one oh 9 two of that exhibit. 10 MR. MYERS: Why don't you read the 11 whole thing, Doctor. They kind of go together, 12 is my recollection, the prior depositions. 13 MR. SMITH: I'm just going to ask one 14 question about one thing. Let me ask you, and if 15 he needs clarification, I certainly will let him 16 do this. 17 MR. MYERS: Sure. 18 A. What page again, please? 19 Q. It's two one oh two. Do you 20 see where in the middle of the page, above that, 21 where there's a mark on the xeroxed copy where it 22 says page five? 23 A. Yes. 24 Q. Where it says under suicidal Page 201 1 thinking in clinical trials, you may want to note 2 that trials were not intended to address issue of 3 suicidality. Also in paragraph two, patients 4 were excluded who were serious suicidal risks. 5 Do you see that? 6 A. Yes. 7 Q. Do you agree with Doctor 8 Heiligenstein that the trials were not intended 9 to address the issue of suicidality? 10 A. Yes, I have already stated 11 that with regard to the depression trials. I'm 12 not sure what Doctor Heiligenstein is -- which 13 trials he's referring to here, but presuming that 14 it was the depression trials, or any other trial 15 for that matter, that would be the case, yes, the 16 trials were not intended to address suicidality. 17 Q. And do you agree that the 18 trials that were, at least, the subject of your 19 paper, all were done under protocols that 20 excluded serious suicidal risks? 21 A. No, there were -- there was at 22 least one, and I believe two, studies where there 23 was not an exclusion criteria. 24 Q. Did you have some inpatient Page 202 1 studies in your -- 2 A. Yes. 3 Q. -- clinical trial analysis? 4 All the outpatient studies, suicide -- serious 5 suicidal risk were excluded, were they not? 6 A. That's correct. 7 Q. I only see two trials that 8 were included in your review that excluded 9 serious suicidal risk. 10 A. I believe that number is 11 correct. 12 MR. MYERS: Paul, I couldn't hear you. 13 Did you say included or excluded? 14 MR. SMITH: I didn't want you to hear 15 me, it was a secret between Doctor Beasley and 16 myself. 17 MR. MYERS: Did you hear him? 18 THE WITNESS: Yes, I did. 19 MR. SMITH: Why don't you read the 20 question back, please. 21 (THE COURT REPORTER READ BACK THE 22 REQUESTED TESTIMONY.) 23 A. He used included correctly, 24 then referred to the number that were included in Page 203 1 the analysis that excluded suicidal risk. 2 Q. Of the trials, seventeen 3 trials analyzed by you reflective of your 4 meta-analysis, Doctor Beasley, fifteen of those 5 trials excluded patients who were serious 6 suicidal risk? 7 A. That's correct. 8 Q. Two of those trials included 9 patients who were serious suicidal risk? 10 A. Could include patients. 11 Q. Could include, all right. 12 That's significant because serious suicidal risk 13 was not an exclusion criteria in those two 14 trials. 15 A. I'm sorry, could you repeat 16 that question again? 17 Q. That is significant because 18 serious suicidal risk was not an exclusion 19 criteria in the protocol of those two inpatient 20 clinical trials. 21 A. That's correct. 22 Q. In those trials that could 23 possibly include individuals who are serious 24 suicidal risk, was a small, small minority in Page 204 1 numbers, was it not? 2 A. That's correct. 3 Q. And an overwhelming eighty to 4 ninety percent majority of the trials that were 5 analyzed excluded individuals who were suicidal 6 risks? 7 A. Who were, again, by clinical 8 definition -- by clinical interview, judged to be 9 at serious or significant suicidal risk. 10 Q. Well, is there any way, any 11 protocol that determines significant suicidal 12 risk is used? 13 A. I believe the term is 14 exclusively serious. 15 Q. Your analysis indicates that 16 only three individuals committed suicide while 17 under -- while participating in the clinical 18 trials that you reviewed, don't they? 19 A. I would need to -- 20 MR. MYERS: Are you referencing a 21 particular citation? 22 Q. Look on page -- look under 23 suicidal acts on page eight ninety-nine of your 24 paper. It says during the single-blind placebo Page 205 1 lead-in period of these trials, three suicidal 2 acts were identified. One of these patients was 3 continued in the trial randomized to Fluoxetine, 4 and completed the double-blind treatment without 5 any further suicidal act. 6 A. That's correct. 7 Q. All right. Then you say on 8 page eight ninety that the occurrence of three 9 suicidal acts during the brief placebo lead-in 10 period in a population screened to exclude 11 serious suicidal risk, emphasizes the inherent 12 danger of suicidality, correct? 13 A. Which page, please? 14 MR. MYERS: Eight ninety. 15 MR. SMITH: Well, maybe I've got two 16 different -- 17 Q. It's six eighty-nine. 18 A. Six eighty-nine. I was 19 looking at it upside down. 20 Q. Look under discussion. 21 A. Right. 22 Q. Do you see that there? 23 MR. MYERS: Which paragraph, Paul, 24 under discussion? Page 206 1 MR. SMITH: Under the paragraph 2 discussion, the first paragraph, the first 3 sentence, the occurrence. 4 A. The occurrence of three 5 suicidal acts during the brief placebo lead-in 6 period. 7 Q. Now. Actually, Doctor 8 Beasley, there were more than three suicidal acts 9 that occurred during the clinical trials, weren't 10 there? 11 A. We're referring to these 12 clinical trials. 13 Q. Any of the clinical trials 14 that were done up to there? 15 MR. MYERS: The ones from the paper or 16 all trials? 17 MR. SMITH: All trials. 18 A. Yes. 19 Q. How many had been done up to 20 December of 1989? 21 A. I don't recall the specific 22 number. 23 Q. What is your best 24 recollection? Page 207 1 A. I'm sorry, but again, orders 2 of magnitude, I believe it was greater than ten, 3 it was probably in the tens in terms of suicidal 4 acts in the clinical trials. 5 Q. Okay. We'll show you -- and 6 you don't have to be sorry, we'll show something 7 that would help you. 8 (DISCUSSION OFF THE RECORD.) 9 (PLAINTIFFS' EXHIBIT NO. 4 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 Q. Doctor Beasley, Exhibit 4 13 indicates that up to December 14th, 1990 -- 14 MR. MYERS: Paul, I don't think he's 15 finished looking at it. 16 MR. SMITH: I'm sorry. 17 MR. MYERS: I looked at it first. 18 A. Yes, I have looked at the 19 document. 20 Q. Exhibit 4 -- you were copied 21 in, by the way, on that document, were you not? 22 A. Yes, I see my name under the 23 third -- 24 Q. And that's dated December 21, Page 208 1 1990, isn't it? 2 A. That's correct. 3 Q. And that's ten months before 4 this article was published, isn't it? 5 A. That's correct. 6 Q. And you had information that 7 through December 14, 1990 that you had had a 8 hundred and ninety-eight suicide deaths in the 9 United States, hadn't you? 10 A. Yes. May I ask a question? 11 MR. MYERS: If you don't understand 12 what he's asking, ask him. 13 A. Well -- well, let's -- this is -- 14 Q. It also indicates that you had 15 data in your DEN reporting system, which included 16 clinical trial and spontaneous post-marketing 17 reports, that there were ninety-four deaths 18 outside the United States. 19 A. That's correct. 20 Q. So you had actually almost 21 three hundred deaths that had been reported by 22 suicide by individuals taking Prozac ten months 23 earlier than this article was written, didn't 24 you? Page 209 1 A. Yes. 2 Q. And that's not anywhere 3 reflected by -- in any way reflected in your 4 paper, is it? 5 A. No. 6 Q. Additionally, there were 7 reports of either thirteen or fifteen deaths that 8 had occurred in the clinical trials up to the 9 time this paper was written, were there not? 10 A. I don't recall the specific 11 number of deaths in the clinical trials. That 12 was the question, I thought that you had 13 initially asked -- 14 Q. It was, it was. 15 A. -- me before we reviewed the 16 document. 17 Q. So -- 18 A. And -- 19 MR. MYERS: Go ahead and fininsh, 20 Doctor Beasley. 21 A. And I say it would be 22 difficult for me to give you that specific 23 number, I indicated a domain of an order of 24 magnitude, that it would have been in the tens. Page 210 1 Q. Now, equally important, Doctor 2 Beasley, there's no discussion in your paper, is 3 there, about the fact that patients that 4 participated in these trials may well have 5 received concomitant medications such as sleeping 6 medicines and sedatives? 7 A. That's not mentioned in the 8 paper, no. 9 Q. But in those seventeen trials, 10 patients were receiving agents for sleep and 11 agents for anxiety, were they not? 12 A. They could have been, yes. 13 Q. But in fact were, weren't 14 they? 15 A. A percentage of patients were, 16 yes. 17 Q. You didn't feel it was 18 relevant to report that? 19 A. No, I did not. 20 Q. Did you know at the time that 21 the German government was requiring Lilly to have 22 in their packaging information that it was 23 recommended that in patients with suicidal risk, 24 they be given tranquilizers for the first few Page 211 1 weeks of treatment? 2 A. No, I did not. 3 Q. Do you know that today? 4 A. You've just indicated it to 5 me. 6 Q. Never heard of that before 7 now? 8 A. Actually it came up in 9 discussion with counsel, I believe, yesterday. 10 MR. MYERS: Right. Don't disclose 11 anything more about it. 12 MS. ZETTLER: He waived it, Larry. 13 MR. MYERS: He hadn't waived anything. 14 MR. SMITH: Is there some tint to 15 those glasses. 16 MR. MYERS: No, it's that glare off 17 your forehead reflected in my glasses. 18 (PLAINTIFFS' EXHIBIT NO. 5 WAS 19 MARKED FOR IDENTIFICATION AND 20 RECEIVED IN EVIDENCE.) 21 Q. I'm going to help you, Doctor, 22 and ask you to turn to page three of the document 23 marked Exhibit 3, then I'll tell you that that's 24 a translation of the German package insert for Page 212 1 Fluoxetine, which is Prozac. Will you take my 2 representation? 3 A. Yes. And you asked me to turn 4 to page three? 5 Q. Yes. Actually it says page 6 two on the top of the page. 7 A. Yes. 8 Q. See where it says risk 9 patients? 10 A. Yes. 11 Q. See where it says risk of 12 suicide? 13 A. Yes, I do. 14 Q. Fluctin does not have a 15 general sedative effect on the central nervous 16 system, therefore for his or her own safety, the 17 patient must be sufficiently observed until the 18 antidepressant effect of Fluoxetine sets in. 19 Taking an additional sedative may be necessary. 20 This also applies in cases of extreme sleep 21 disturbances or excitability. Do you see that? 22 A. Yes, I do. 23 Q. And I'll represent to you that 24 that -- that Fluctin is Prozac in Germany. Did Page 213 1 you know that? 2 A. Yes. 3 Q. And that this is the patient 4 prescribing information, but you have never seen -- 5 A. No. 6 Q. -- this before? 7 A. No. 8 Q. Do you have any criticism of 9 this language? 10 A. Yes, I do. 11 Q. All right. What would be your 12 criticism of this language, Doctor Beasley? 13 A. First of all, with regard to 14 the first sentence, Fluoxetine does not have a 15 general sedative effect on the central nervous 16 system. As I indicated, there are a number of 17 trials which indicated, in fact there is a 18 statistically significant increased incidence of 19 somnolence, asthenia, psychomotor slowing 20 associated with the compound. So this is as a 21 general categorical statement, I disagree with. 22 Q. How would you say that to make 23 it more scientifically accurate? 24 A. Uh -- Page 214 1 Q. Are you saying it's 2 scientifically inaccurate? 3 A. In my opinion, that first 4 sentence is less than accurate. 5 Q. All right. 6 A. And it has to do with this 7 issue of some patients in fact becoming sedated. 8 Q. If I were to ask you, Doctor 9 Beasley, is Prozac a sedative, what would you 10 say? 11 A. It's not -- before I answer, 12 let me ask you to define sedative for me. 13 Q. Something that makes you -- 14 that doctors prescribe for sleeping agents or 15 calming agents. 16 A. And could I presume that as 17 part of that definition, it would put -- it would 18 make the majority of people sleepy? 19 Q. Yes. 20 A. Over fifty percent? 21 Q. Yes. 22 A. Then I would not characterize 23 Prozac in that fashion. 24 Q. All right. So what would be Page 215 1 inaccurate about saying Fluctin does not have a 2 general sedative effect on the central nervous 3 system? 4 A. There are a substantial number 5 of patients who in termporal association with 6 ingestion of Fluoxetine, do become sedated. I 7 think the more appropriate way to state this 8 would be -- back to the discussion that we had 9 earlier, that Fluoxetine in the majority of 10 patients does not produce sedation, in some 11 patients sedation would be observed. 12 Q. All right. 13 A. So that's the first -- 14 Q. If you said Fluctin does not 15 have a general sedative effect on the majority of 16 individuals, would that be an accurate statement? 17 A. That would be an accurate 18 statement, yes. 19 Q. Anything else you have any 20 criticism about this language? 21 A. Actually, yes. The next set 22 of statements, therefore for his/her own safety, 23 the patient must be sufficiently observed until 24 the antidepressant effect of Fluctin sets in. Page 216 1 Taking an additional sedative may be necessary. 2 I am not personally aware of data that supports 3 the position that depressed patients should be 4 sedated until they have core mood disturbance 5 relief, their depressed mood relieved. 6 Q. Well, you know Doctor Jan 7 Fawcett, don't you? 8 A. Yes, I do. 9 Q. You know he is a well 10 respected psychiatrist? 11 A. Yes, I do. 12 Q. And you even thanked him in 13 your meta-analysis paper, didn't you? 14 A. Yes, I did. 15 Q. Do you know he's on the Lilly 16 psychiatric advisory board? 17 A. Yes. 18 Q. He's held in respect by you? 19 A. Yes. 20 Q. And by your colleagues at 21 Lilly? 22 A. Yes. 23 (PLAINTIFFS' EXHIBIT NO. 6 WAS 24 MARKED FOR IDENTIFICATION AND Page 217 1 RECEIVED IN EVIDENCE.) 2 Q. Have you read Doctor Fawcett's 3 article published in the Journal of Clinical 4 Psychiatry titled Targeting Treatment in Patients 5 with Mixed Symptoms of Anxiety and Depression? 6 A. I don't recall reading this 7 article. 8 Q. Well, it was published in 9 November of 1990 and presented at the APA 10 Association in New York meeting in May, 1990. 11 A. Yes. 12 Q. Did you go to that meeting? 13 A. I went to that meeting. I was 14 not present -- I don't recall being present at 15 that talk. 16 Q. Obviously treating patients 17 with mixed symptoms of anxiety and depression is 18 a subject that is of relevance to the issue 19 presented by your meta-analysis, is it not? 20 A. I don't believe that my 21 meta-analysis here brings up that issue. 22 Q. It's a subject that certainly 23 could be addressed by this German package insert? 24 A. Absolutely. Page 218 1 Q. Turn with me to page forty-two 2 of that article, and look under combination 3 therapy where it's talking about suicide 4 prevention. 5 A. Yes. 6 Q. You read there where Doctor 7 Fawcett says aggressive treatment with a 8 benzodiazepine anxiolytic is indicated for 9 immediate relief of anxiety in patients with 10 major depression if they manifest risk factors 11 for suicide. If the anxiety is severe or if the 12 antidepressant selected causes jitteriness, 13 paren, Fluoxetine, or is without sedative 14 properties, paren, Desipramine, Imiprimine, 15 Bupropion, paren, period, close quote. Do you 16 see that? 17 A. Yes. 18 Q. So you see there that Doctor 19 Fawcett is apparently disagreeing with you that 20 patients should not be treated with Prozac and a 21 sedative? 22 A. Could you read that back to 23 me, please? 24 (THE COURT REPORTER READ BACK THE Page 219 1 REQUESTED TESTIMONY.) 2 A. I would agree with you that 3 this reflects an opinion of Doctor Fawcett that I 4 would see as being different from mine if he's 5 referring to patients in general. I think that 6 we were talking about patients in general based 7 off the package insert as a sort of categorical 8 statement that all patients should receive this. 9 I believe that Doctor Fawcett is talking about 10 patients who do manifest activation, as he 11 specifically characterizes it, anxiety, jitters. 12 Q. The package insert says 13 therefore, for his/her own safety, the patient 14 must be sufficiently observed until the 15 antidepressant effect of Fluctin sets in. Taking 16 an additional sedative may be necessary, doesn't 17 it? 18 A. That's correct. 19 Q. The German package insert says 20 that taking an additional sedative may be 21 necessary, doesn't it? 22 A. Yes, it does. 23 Q. Doctor Fawcett says that in 24 his article, does he not? Page 220 1 A. I read Doctor Fawcett's 2 statement to be, again, if anxiety is severe or 3 if the antidepressant selected causes 4 jitteriness, those without sedative properties, 5 then a benzodiazepine would be appropriate to 6 take. 7 Q. Of course you conveniently 8 left out that word -- after if the antidepressant 9 causes jitteriness, you left out the word 10 Fluoxetine, didn't you? 11 A. Yes. 12 Q. Because this doctor -- that 13 implies, does it not, that it's Doctor Fawcett's 14 opinion that in some patients Prozac causes 15 jitteriness, and when that occurs, those patients 16 should have a sedative such as benzodiazepine, 17 doesn't it? 18 A. I believe that is Doctor 19 Fawcett's opinion reflected here. 20 Q. Do you disagree with that 21 opinion? 22 A. I could not agree with it on a 23 categorical basis, I think it would need to be an 24 individual physician/patient decision. Page 221 1 Q. So what would be wrong then in 2 the German package insert information that says 3 taking an additional sedative may be necessary? 4 A. We were, I believe, actually 5 discussing the sentence prior to that. 6 Q. Were we? I thought your 7 complaint was that there's -- that you shouldn't 8 have sedative treatment with individuals? 9 A. No, it was the sentence before 10 that, therefore for his/her own safety, the 11 patient must be sufficiently observed until the 12 antidepressant effect of Fluctin sets in. As I 13 understand the first, and the second, sentence, 14 there's this presumption that because Fluoxetine 15 is not sedating, there may be some particular 16 unspecified risk to the patient during the early 17 treatment. I have issue with that. In the 18 abstract, taking an additional sedative may be 19 necessary, clearly in some patients it would be 20 appropriate to administer a benzodiazepine during 21 early stages or later stages of depression, I 22 don't have a problem. 23 Q. In fact that was occurring in 24 many of the clinical trials that you used in your Page 222 1 meta-analysis, wasn't it? 2 A. Yes, it was. 3 Q. So what would be the problem? 4 I mean it sounds to me like the German package 5 insert isn't saying anything more than what you 6 all were in fact doing in the clinical trials 7 under analysis that you say support the fact that 8 Prozac doesn't cause suicidality. 9 MR. MYERS: Let me object to the form 10 of the question because that simply is your -- 11 that's your statement or testimony as to what you 12 think, I don't think that's even in the form of a 13 question. 14 Q. I said what would be wrong 15 with -- 16 MR. MYERS: Well, to that extent, I 17 think he's asked and answered what is wrong with 18 the language in the insert. 19 MS. ZETTLER: It's a different 20 question, Larry. 21 MR. MYERS: Go ahead and answer it if 22 you can. 23 A. Let me try to understand the 24 question. What would be wrong with -- help me Page 223 1 out. What would be wrong with -- 2 Q. Doctor Beasley, in the 3 clinical trials, patients were receiving 4 concomitant medications, weren't they? 5 A. Yes. 6 Q. In the clinical trials that 7 are the subject of your paper, patients were 8 receiving concomitant medications, weren't they? 9 A. Yes. 10 Q. In the clinical trials that 11 were the subject of your paper, the patients were 12 receiving benzodiazepines, weren't they? 13 A. Yes. 14 Q. Sedatives, weren't they? 15 A. Yes. 16 Q. And Lilly had no problem with 17 that, did they? 18 A. No. 19 Q. So in this package insert 20 prescribing information for German patients, it's 21 merely suggesting that some patients may require 22 a sedative if they don't have sedating effects of 23 the Prozac, correct? 24 MR. MYERS: Let me object -- hold on, Page 224 1 let me object to the form of the question that 2 you've selected would characterize what's in the 3 insert and mischaracterized what he said. Go 4 ahead and answer. 5 A. Again, I'm afraid that I read 6 the package insert differently. I read in the 7 first two sentences an implication as to why 8 patients should be treated with a concomitant 9 benzodiazepine, particularly in the second 10 sentence that there's something about 11 non-sedating antidepressants that require them to 12 have concomitant -- or concomitant benzodiazepine 13 or sedative hypnotic administration occur 14 concurrently. That's what I'm disagreeing with. 15 Q. I'm not asking you whether you 16 disagree or agree at this point, Doctor, I'm 17 asking you isn't it a fact that what is 18 occurring, as per the recommendation in the 19 German package insert, is exactly what you all 20 did in the clinical trials? 21 MR. MYERS: Same objection. 22 A. Benzodiazepines and/or other 23 sedative hypnotics were administered to some 24 patients in clinical trials. The third sentence Page 225 1 in this, taking an additional sedative may be 2 necessary, I take that as a statement that would 3 be consistent with the practice in the clinical 4 trials, but not as related to risk of suicide. 5 Q. Whether it's related to the 6 risk of suicide or not, Doctor Beasley, the 7 practice recommended by the German package insert 8 is exactly what was allowed by Lilly in their 9 clinical trials, wasn't it? 10 MR. MYERS: Same objection. Go ahead 11 and answer. 12 A. I'm sorry, but I think I just 13 indicated that in fact this one particular 14 sentence, that actually has a concrete statement 15 about patient care, was in fact consistent with 16 what was allowed, again, allowed, in Lilly 17 trials, taking that one sentence. 18 Q. No, taking the entire thing. 19 I mean all -- the German package insert says, 20 whether you agree with it or not, that Fluctin 21 does not have a general sedative effect on the 22 central nervous system, correct? 23 A. That's what this sentence 24 says. Page 226 1 Q. Obviously Lilly felt that 2 there were some individuals who participated in 3 the clinical trials that reacted in the same 4 manner because they allowed concomitant 5 medications for sleep and for reduction of 6 agitation, did they not, in the clinical trial 7 protocol? 8 A. That's correct. 9 Q. So whether all people are 10 agitated and activated by Prozac, certainly is 11 not the issue. The issue is do you allow 12 sedatives and tranquilizers and hypnotics for 13 some individuals that don't get a sedating effect 14 from Prozac, correct? 15 A. Excuse me, but your question 16 also just carried the implication that Prozac 17 was, as I understood it, causally related to 18 these events in all patients. Again -- 19 Q. No, I didn't mean to imply 20 that. But in some patients, certainly. In the 21 clinical trials, not all patients were given 22 benzodiazepines and chloral hydrate, were they? 23 A. That's -- not all patients 24 were, that's correct. Page 227 1 Q. And this package insert 2 doesn't recommend that all patients receive 3 sedatives, does it? 4 A. No, and it qualifies itself 5 with maybe. 6 A. Yes. 7 Q. Yes. 8 A. That's correct. 9 Q. So there's certainly no clear 10 indication that every time you prescribe Prozac, 11 you ought to prescribe a sedative, does it? 12 A. No. 13 Q. The clear implication of that 14 is if -- a sedative may be necessary for 15 individuals who take Prozac, correct? 16 A. I'm sorry, but again, I think 17 I've -- 18 MR. MYERS: Go ahead, Doctor, and 19 answer. 20 A. I think I've agreed with you 21 with the qualification. 22 Q. I think you have, too, I just 23 want to -- 24 MR. MYERS: Let him finish now, Paul. Page 228 1 MR. SMITH: I'm just trying to agree 2 with him. I'm not trying to cut him off, 3 seriously. 4 A. With the qualification that 5 given the context in which this statement exists, 6 and my understanding, my interpretation of the 7 reason for making the statement, I disagree with. 8 Q. I understand that. I'm 9 talking about, though, what this insert calls for 10 and what was actually occurring in the clinical 11 practice of the clinical trial, okay. I want to 12 examine those two things together, whether or not 13 you've got risk of suicide associated with either 14 one, all right? 15 MR. MYERS: Is that a question or are 16 you sort of setting up a question? 17 MR. SMITH: I'm setting up a question, 18 and I want to see if he follows it. 19 MR. MYERS: Do you follow him to that 20 point? 21 A. Again, I think we've been 22 approximately saying the same thing, which is 23 that sedative hypnotics were administered to some 24 patients in the clinical trials. Page 229 1 Q. Yes. 2 A. And here's a statement in the 3 German package literature, embedded in a 4 paragraph that I don't like, with one statement 5 regarding clinical recommendation for sedatives 6 that's clearly consistent with the practice in 7 the clinical trials. 8 Q. Okay. 9 A. Have we -- 10 MS. ZETTLER: Basically you have no 11 problems with administering sedative hypnotics to 12 people on Prozac if they require it because of 13 agitation or insomnia, regardless of whether or 14 not it's in the clinical setting. 15 MR. MYERS: Whether or not it's in the 16 clinical setting or clinical trial setting? 17 MS. ZETTLER: That's what I meant, 18 clinical trial setting. 19 THE WITNESS: I have no problem with 20 the concomitant administration of the two 21 medications. 22 MS. ZETTLER: Okay. 23 THE WITNESS: I'm not aware of any 24 reason to categorically recommend that Page 230 1 co-administration. 2 MS. ZETTLER: Nobody is suggesting 3 that, Doctor. 4 THE WITNESS: Okay. 5 MR. MYERS: You asked him to answer 6 the question. 7 MS. ZETTLER: All I said is you have 8 no problems if a -- if a patient requires it, 9 because of agitation or insomnia, which you 10 agreed with Paul earlier might be a couple of 11 reasons why you might want to co-administer a 12 hypnotic or other sedatives, correct? 13 MR. MYERS: Answer the question for 14 the last time. 15 MS. ZETTLER: Right, that's what you 16 said earlier? 17 THE WITNESS: I agreed that patients 18 did receive benzo -- sedative hypnotics in the 19 clinical trials. And as I understood your 20 question to me, you asked did I have a problem 21 with that, and I understood that to mean did I 22 know of any reason why that would not be good 23 clinical practice. 24 MS. ZETTLER: No. You're reading too Page 231 1 much into my question. My question is: Do you 2 have a problem in the patient that requires it, 3 who is on Prozac, okay? I'm not saying across 4 the board or anything like that, but a patient 5 who is either suffering from insomnia or 6 agitation or something along those lines, do you 7 have a problem with the co-administration of a 8 concomitant benzodiazepine or sedative hypnotic? 9 THE WITNESS: You're asking me about a 10 hypothetical specific patient? 11 MS. ZETTLER: Right. 12 THE WITNESS: I think it would be a 13 matter, again, of clinical judgment. I have no 14 reason to state absolutely that no individual 15 patients should receive a benzodiazepine. 16 Mister ZETTLER: All right. 17 MR. MYERS: Can we have a break? 18 MR. SMITH: Sure. 19 (A SHORT RECESS WAS TAKEN.) 20 Q. (BY MR. SMITH) Doctor 21 Beasley, were there only seventeen United States 22 double-blind clinical trials in patients with 23 major depressive disorders comparing Fluoxetine 24 with a tricyclic or a placebo or both at the time Page 232 1 your paper was written? 2 A. That's correct, that all the 3 data here represented the entirety of the 4 controlled clinical trials that have been 5 conducted. 6 Q. In the United States? 7 A. In depression. 8 Q. In depression? 9 A. In depression. 10 Q. All right. And in the United 11 States? 12 A. That's correct. 13 Q. In other words, there were 14 other double-blind controlled clinical trials 15 with placebo arms in existence comparing 16 Fluoxetine or examining Fluoxetine for other 17 indications other than depression that had been 18 completed? 19 A. Yes. 20 Q. And there were other 21 double-blind clinical controls with placebo arms 22 in depressive studies outside the United States? 23 A. That's correct. 24 Q. Why didn't you use the outside Page 233 1 United States double-blind placebo armed 2 controlled studies? 3 A. You're referring specifically 4 to this paper? 5 Q. Yes. 6 A. They had not been analyzed at 7 the time this paper was completed. 8 Q. Well, they had been completed, 9 hadn't they? 10 A. That's correct. They had not 11 been submitted to a similar analysis at the time 12 this paper was completed. 13 Q. What type of analysis are you 14 talking about? 15 A. The analyses that are 16 reflected here of suicidality. Those trials were 17 in fact analyzed separately. 18 Q. Is that when you went over 19 there with a team of people and collected data 20 and then you and Doctor Heiligenstein, and maybe 21 Doctor Masica, reviewed event terms and reviewed 22 clinical report forms to determine whether or not 23 the act indeed was a suicidal ideation or 24 suicidal act? Page 234 1 A. That information did have to 2 be collected and placed into a unified data base 3 to analyze in this fashion, because it did not 4 exist in a computer in the United States. 5 Q. Are you telling me that -- in 6 that analysis, there were some acts that had been 7 reported as suicidal ideations or suicidal 8 gestures that we've learned were determined by 9 you and Doctor Heiligenstein to not in fact be 10 suicidal acts or gestures? 11 A. There may have been reports 12 that were brought to our attention. By that I 13 mean on the clinical report forms that were 14 brought back, which did not meet the definitions 15 that were set up for the -- for these two 16 reports. 17 Q. Okay. So was there an earlier 18 analysis made of the U.S. double-blind placebo 19 controlled data? 20 A. Yes. We reviewed, either 21 electronically or in person, first screening by 22 the CRAs, and then by the clinical research 23 physicians, the entirety, again, of the clinical 24 trial data base as an additional quality review Page 235 1 step before completing analysis. 2 Q. Okay. Were the number of acts 3 reduced by you in the United States as you had in 4 the outside U.S. studies? 5 A. Actually the number of acts 6 was increased. 7 Q. In the United States? 8 A. That's correct. 9 Q. But it was decreased in the 10 outside the United States studies? 11 A. I'm not certain what you're 12 referring to there. 13 Q. We deposed Catherine Mesner. 14 Do you know who she is? 15 A. Yes. 16 Q. And she was intimately 17 involved in helping you all in this analysis of 18 the OUS data, correct? 19 A. That's correct. 20 Q. And she went over to Europe 21 and collected case report forms and brought back 22 a number of forms that indicated suicidal acts or 23 gestures? 24 A. That may have indicated Page 236 1 suicidal acts or gestures as well as suicidal 2 ideation. 3 Q. When she brought it back to 4 the United States, you and Doctor Heiligenstein, 5 and perhaps Doctor Masica, went through that. 6 A. That's correct. 7 Q. And reduced from the OUS data 8 the number of events. 9 A. We may have. I don't recall 10 specifically any cases that we included or 11 excluded as meeting the conditions that we 12 specified. 13 Q. Don't you recall, Doctor 14 Beasley, that you reduced the number by eighty or 15 ninety percent? 16 A. No. 17 Q. Instead of marking this whole 18 thing, I'm just going to read portions of the 19 deposition testimony of Ms. Mesner to you, Doctor 20 Beasley. 21 A. Certainly. 22 Q. On page fifty-five, she was 23 asked how about OUS -- how about the OUS hits, do 24 you recall how many hits you pulled. Her answer Page 237 1 there was hundreds. Then on page sixty, she was 2 asked, so ten to twenty percent of the hits that 3 you and your coworkers initially submitted to the 4 clinical research physicians at Lilly in 5 Indianapolis for review related to suicidality 6 were determined by those doctors to be in fact 7 related to suicidality, answer, yes. Do you see 8 that? 9 A. Yes. 10 Q. Do you disagree with that? 11 A. No, I don't disagree with 12 that. 13 Q. So -- 14 A. I -- 15 MR. MYERS: Go ahead and finish. 16 A. I have concerns about the 17 definition of hit. The individuals who were sent 18 to Europe were sent with the instructions to 19 capture very, very widely anything that -- again, 20 them not being clinicians might even potentially 21 suggest suicidal ideation or suicidal acts. That 22 data base was substantially reduced, I'm fairly 23 certain of that. The extent to which there was a 24 concrete act that had been explicitly reported on Page 238 1 a case report form that had been rejected, I 2 don't recall the number of those, if there were 3 any. Again, we set, in my belief, a very wide 4 standard for classifying things which might 5 generally be thought of as gestures, as acts. We 6 may have excluded some based on the temporal 7 relationship to the time which the patient ended 8 the clinical trial. Again, we had captured a 9 great number of instances where there were 10 suggestions of suicidal ideation that would have 11 been incorporated into our Ham-D item three 12 analysis, and not -- there were not suicidal 13 acts, there were notes or notations made 14 regarding suicidal ideation. 15 Q. What definitions did you give 16 the clinical research associates? 17 A. Basically anything that in 18 their estimate would even begin to suggest a 19 suicidal ideation or suicidal act should be 20 brought back to us for review. 21 Q. Give me an example of 22 something they brought back to you for review 23 that you indicated was not indicative of 24 suicidality? Page 239 1 A. I think -- excuse me, I think 2 we began by discussing suicidal acts, is that -- 3 Q. Or ideation. Weren't you 4 looking for both? 5 A. We were looking for ideation 6 for which we used the Ham-D item three, and in 7 fact in the trials in which it was available, the 8 MADRS as an item. 9 Q. Okay. So weren't you looking 10 for acts or ideations? 11 A. We were looking to make very 12 certain that we counted correctly the number of 13 acts that had occurred. We were willing to look 14 at anything that suggested even a mention of 15 ideation to count those acts, and we wanted to 16 make very certain that we had captured accurately 17 the Ham-D item three, and the MADRS, if it 18 existed. 19 Q. So you weren't counting 20 ideation, you were just counting acts? 21 A. We were counting -- the 22 analysis that were done, okay, counted acts, 23 counted a particular analysis of the Ham-D item 24 three, which was the zero-one to three-four. Page 240 1 Q. So that's going to have to 2 include ideation, then, isn't it, Doctor? 3 A. That's correct. 4 Q. Okay. 5 A. And all of that information on 6 every patient in the entire European controlled 7 data base is in fact reflected in those analyses 8 of the Ham-D item three and the MADRS, where it 9 existed. 10 Q. So give me an example of 11 something that the clinical research assistants 12 brought back to you that you rejected as a 13 suicidal act or ideation? 14 A. I can't recall any 15 specifically that we rejected as acts where an 16 act had occurred. What I'm saying is we rejected 17 a number of ideations as indicative of acts. 18 Q. So give me an example of that. 19 A. And again, I would have to 20 give you a hypothetical example. 21 Q. Okay. That would be fine. 22 A. There would be some mention in 23 a comment section about suicidal ideation. 24 Q. Okay. Page 241 1 A. Okay? 2 Q. Such as? 3 A. Patient thinking of suicide. 4 Q. Okay. 5 A. And again, no attribution as 6 to whether it had increased or decreased in 7 severity. 8 Q. Patient comes in today -- 9 let's say the comment report -- the comment 10 portion of the case report form says patient 11 comes in today thinking about suicide. That's 12 what you got. 13 A. That's all I got. 14 Q. What would you do with that? 15 A. Okay. That patient is 16 included in the European data base for the 17 Hamilton, and if it existed, a MADRS item. There 18 is nothing in that case report form, given what 19 you just described to me, to indicate that that 20 patient also had a suicidal act. So that patient 21 would be rejected as not having a suicidal act. 22 Q. So now it sounds like you're 23 talking about just suicidal acts that you were 24 counting? Page 242 1 A. Yes. 2 Q. All right. So if a case 3 report form said patient comes in today, said he 4 slit his wrist yesterday, didn't hurt himself 5 really, what would that be? 6 A. That's still a suicidal act. 7 Q. So that would have been 8 accepted, that wouldn't have been rejected? 9 A. The definition, as indicated 10 here, and the definitions were comparable -- 11 Q. Let's don't get these 12 confused, Doctor, because when you say here, 13 you're looking at your meta-analysis, and that 14 doesn't have anything to do with what you were 15 doing in Europe, does it? 16 MR. MYERS: He said the definitions 17 were comparable, that's what he said, Paul. 18 MR. SMITH: But he was using it in the 19 context of here. 20 A. The definition was any act 21 that was undertaken for self harm would be a 22 reasonably expected outcome, unless there was 23 explicit clinical information from the 24 investigator that suicide had not been the Page 243 1 intent. 2 MS. ZETTLER: Such as? 3 THE WITNESS: If the investigator said 4 the -- this patient -- I can recall one U.S. 5 patient of this sort. 6 Q. Wait a second. I thought we 7 were talking about OUS studies. 8 A. She asked me for an example 9 relevant -- 10 MS. ZETTLER: Yes, I asked him for an 11 example of what he would -- what a reporter might 12 say, investigator might say. 13 MR. MYERS: Go ahead, Doctor. 14 THE WITNESS: Patient made what 15 appeared to be ritualistic markings on their 16 body, do not believe this was at all suicidal. 17 MS. ZETTLER: Was this something 18 that's written on a report form or is this 19 something you spoke to that investigator about? 20 THE WITNESS: This would have to be 21 something that was written. 22 Q. Did you speak to any 23 investigators in connection with your OUS 24 investigation? Page 244 1 A. I personally did not, no. 2 Q. Did you conduct any analysis 3 of causation in this massive OUS study? 4 A. And could you help me 5 understand what you mean by analysis of 6 causation? 7 Q. Did you ask anybody whether or 8 not or were you making a determination whether or 9 not the suicidal act was related to the ingestion 10 of Prozac? 11 A. We did not specifically ask 12 investigators. Again, this was -- this data was 13 collected from case report forms, and it was 14 comprehensively taken down. 15 Q. I understand that. 16 A. No, we did not -- to my 17 knowledge, I certainly did not speak with any 18 investigator nor ask any investigator about any 19 of the patients who made suicidal acts. 20 Q. Why? 21 A. By this point in time, we 22 clearly had a signal that some people had made 23 the statement that some patients had had, in 24 their opinion, suicidal acts related, potentially Page 245 1 etiologically, to Prozac. At this point, the 2 focus of what we were doing was to assess whether 3 or not there was a statistical association 4 between Fluoxetine and suicidality as a 5 contribution to this very relevant clinical 6 question. That was the purpose of the -- that 7 was the purpose of the exercise. 8 Q. It just seems relevant to me 9 that the first thing you would do would be to ask 10 the investigator that you had hired to perform 11 the study whether or not in the investigator's 12 opinion he thought the act was related to the use 13 of Prozac. 14 MR. MYERS: I object to the form in 15 what is relevant to you. You want to know if he 16 agrees with you, is that the question? 17 MR. SMITH: The question stands. If 18 you've got an objection, that's fine. 19 MR. MYERS: I've made my objection. 20 A. I'm sorry that I disagree with 21 you. At the time, we were looking for data 22 relevant to large data bases. Our feeling is 23 that an individual investigator basically can't 24 read the mind of his patient or really definitely Page 246 1 know what are the etiologic contributions. We 2 clearly had the issue raised, and we wanted to 3 collect as much objective data as possible, and 4 that was the intent of the exercise. We were 5 certainly willing to make note of any information 6 that the investigator provided. 7 Q. Other than what the 8 investigator's opinion was? 9 A. If an investigator provided 10 it, it was important, we would take it down. 11 Q. Well, was there ever any 12 thought given in making this analysis either in 13 the United States or outside the United States 14 that we'll collect objective data and we'll 15 collect a separate category as much as item four, 16 Ham-D-3 -- the Ham-D-3, four item ideation scale. 17 We'll collect as a separate category, on each act 18 that we find, we'll ask our investigator whether 19 or not, in his opinion, the act was related to 20 Prozac, and then we'll count each one of them and 21 we'll see whether or not the investigator's 22 opinion is statistically significant to the other 23 objective data that we collect, did that ever 24 occur to you to do that? Page 247 1 A. I think you've asked me a 2 couple of questions. We did not systematically 3 collect investigators' opinions, I've indicated 4 that. I'm not sure what comparison you were 5 suggesting. 6 Q. I'm not sure I am either. It 7 would just seem to me, if you were going to all 8 this trouble, if this issue was of some 9 scientific importance, that there should be some 10 analysis or some part of the analysis given to 11 the investigator's opinion who reported the 12 particular act. Did that not seem relevant to 13 you? 14 A. That did not. 15 Q. Okay. Nobody ever suggested, 16 as far as you know, that it might be worthwhile 17 to ask the guy who had been hired by Lilly to 18 fill out the case report form to administer the 19 study whether or not he had an opinion concerning 20 whether or not this particular act was related to 21 the ingestion of Prozac? 22 A. I cannot recall suggesting 23 that, nor can I recall any of my colleague 24 suggesting that. Page 248 1 Q. Now, I wanted to step off in a 2 little different arena and ask you about your 3 review of 1639s individually, all right. Are you 4 following me? 5 A. I believe so. 6 Q. It's been related earlier, in 7 other depositions by Doctor Heiligenstein and 8 Doctor Zerbe, to some extent, that you were 9 reviewing -- the physicians would review 1639s. 10 A. That's correct. 11 Q. And there was follow up -- if 12 necessary, physicians there at Lilly would 13 require particular follow up, correct? 14 A. That's correct. 15 Q. And that you were one of the 16 physicians that was involved in that? 17 A. That's correct. 18 Q. Did you ever, in reviewing a 19 1639, make a determination that the gesture, the 20 suicidal gesture, or completed suicidal act or 21 suicidal ideation reported on the 1639 was 22 reasonably related to the use of Prozac? 23 MR. MYERS: I object to the form only 24 to the extent you've not accurately captured the Page 249 1 regulatory term to make that designation with. 2 A. Do I understand you correctly 3 to be referring to a regulatory determination? 4 Q. Any determination. 5 A. I believe that there would 6 have been occasions, although, again, I cannot 7 specifically remember a specific instance in 8 which I would have checked the box on our DEN 9 report -- that's not the same thing as the 1639 -- 10 but our DEN report as possibly causally related, 11 yes. 12 Q. In what circumstances would 13 you check that box in connection with Prozac and 14 suicide? 15 A. That depends both upon the 16 time and the clinical situation. 17 Q. What about the time and what 18 about the clinical situation would cause you to 19 relate it to Prozac? 20 A. Okay. In the early days of 21 Prozac, both prior to its release and shortly 22 following its release, we adopted a very, very 23 conservative policy with regard to the regulatory 24 checking of the box possibly causally related. Page 250 1 We took the position that we really wouldn't 2 assess the clinical likelihood that in most cases 3 it's really impossible to do that, so we would 4 take the position unless we were absolutely, 5 positively convinced that there was no way an 6 adverse event was associated in any causal way 7 with Fluoxetine, that we would check that box. 8 And I believe that there were suicides, suicidal 9 acts, that were reported to us that would have 10 been translated onto DEN forms, and later to form 11 1639s, to which that position would have applied. 12 During, I believe, sometime in 13 1990, we began to receive a rather new source of 14 reports of adverse events to us, particularly 15 related to suicide, which were lay media reports 16 that we filed, a lot of second-hand and 17 third-hand reports. The report volume was going 18 up considerably. At the time -- at some point in 19 this period, the physicians who were working on 20 the 1639s held a meeting in which the issue of 21 causality was discussed and how to evaluate and 22 assess causality, particularly with the large 23 number of media reports that we were receiving 24 with basically no clinical information. Page 251 1 We, as I recall, as a group, 2 adopted a guideline which was that on reports 3 from health care professionals, if they suggested 4 that there was a causal relationship in their 5 report, then we would take the position of making 6 that possibly causally related. If that was not 7 indicated by a health care professional, we would 8 not. 9 Q. Would you say not related? 10 A. Not related. So again, this 11 was timing, and the last issue being one of the 12 nature of the clinical report. 13 Q. How do you define a report of 14 a health care professional? 15 A. Physician, psychologist, 16 social worker, nurse practitioner. 17 Q. What about a call to one of 18 those individuals by your DISTA representative? 19 A. Those would be reported to us, 20 supposed to be reported to us. 21 Q. Would you consider those 22 reports of health care professionals to which you 23 would assign causation? 24 A. That issue was not explicitly Page 252 1 discussed. If I was aware that the report had 2 been provided to Lilly by a health care 3 professional, whoever they provided it to, be it 4 the call to me or a call to DEU, the drug 5 epidemiology unit, or to any other Lilly 6 representative, I would consider that to be a 7 health care professional. 8 Q. So I'll be clear, if a DISTA 9 representative goes by making a regular routine 10 call on a physician, and that physician advises 11 the DISTA representative that they have an 12 adverse experience with Prozac involving suicidal 13 acts or ideation, then that DISTA representative 14 is instructed to report that to the DEN system, 15 are they not? 16 A. That's correct. 17 Q. If that DISTA representative 18 reports that to you, do you treat that as a 19 report by a health care professional? 20 A. I certainly would, presuming 21 that it was clear that the report was made by a 22 health care professional. 23 Q. I understand that. 24 A. Right. Page 253 1 Q. I would assume that the DISTA 2 representative would identify where she or he 3 received that information, correct? 4 A. I would certainly hope so. 5 Q. Now, if a DISTA representative 6 is in Waco, Texas, and reads in the Waco Tribune 7 that somebody has had a suicide and that that 8 individual was on Prozac, they're to report that, 9 are they not? 10 A. I would believe that that 11 would be consistent with our policy. 12 Q. But that newspaper report by 13 you would not be considered as a health care -- 14 something submitted by a health care professional 15 that would cause you to make a determination to 16 causality? 17 A. That would be correct. 18 Q. When was it that you changed 19 your policy in characterizing 1639s? 20 A. I think I indicated what I 21 believe to be an approximate time earlier which 22 would have been, I believe, again, sometime in 23 1990. 24 Q. All right. So it would have Page 254 1 been within a few months from the date of the 2 Teicher publication? 3 A. It may have been more than two 4 or three, I don't recall. 5 Q. At least by the summer of 6 1990, you probably changed your method of 7 handling the 1639s. 8 A. Again, that's an 9 approximation. Whether it was early summer or 10 late summer, fall, I can't recall, I'm sorry. 11 Q. Well, look again with me at 12 Exhibit 3, on page twenty-one oh one, and this is 13 Doctor Heiligenstein's comment to Doctor Leigh 14 Thompson. They copied you. Did you review this 15 presentation that Doctor Thompson was going to 16 make to the board concerning Prozac and 17 suicidality that's mentioned here? 18 A. Let me -- 19 MR. MYERS: He didn't look at the 20 whole exhibit last time. 21 Q. Why don't you -- it would 22 probably be better at this time if you would look 23 through this entire exhibit and let me ask you 24 some questions about it. Page 255 1 A. Okay, I have read the 2 document. 3 Q. It appears, Doctor, that that 4 document is reflective of a presentation that 5 Doctor Leigh Thompson was going to make to the 6 board of directors and/or Mister Wood, correct? 7 A. I see Mister Wood's name 8 mentioned here, and I understand it to be a 9 presentation for his benefit. 10 Q. And do you recall reviewing 11 some data and some slides and some verbatim or 12 verbatims that Doctor Thompson was going to 13 review with Mister Wood? 14 A. As I recall, Doctor Thompson, 15 on several occasions, sending me material to 16 review. I can't recall any specific instance or 17 material that I reviewed. Doctor Heiligenstein's 18 note to Doctor Thompson suggests that I did 19 review this specific material. 20 Q. Because it says on page 21 twenty-one oh one, Charles, David and I have 22 reviewed your presentation and offered the 23 following thoughts and comments, correct? 24 A. That's correct, that's what I Page 256 1 was referring to. 2 Q. And then you kind of got in 3 some trouble. Look at the top of the page. 4 Doctor Thompson says thank you for your comments, 5 but they are late. I gave the draft to Dan and 6 Bob early Monday morning with request for them to 7 proof and verify the numbers, et cetera, et 8 cetera. It goes on to say I'm very upset that I 9 can, on Friday morning -- that I get on Friday 10 morning this response to my Monday morning 11 request. Specifically when the slides were made 12 entirely from material that Dan gave me on Friday 13 afternoon. Do you see that? 14 A. Yes. 15 Q. So would you characterize 16 Doctor Thompson as being upset by virtue of what 17 he says there? 18 A. Well, it's difficult for me to 19 know specifically what was going on in Doctor 20 Thompson's mind, but I take the tone of this as 21 being less than satisfied. 22 Q. All right. How often were you 23 interacting with Doctor Thompson on this issue at 24 that time? Page 257 1 A. It was variable, but I would 2 say -- and again, we're talking face-to-face or -- 3 Q. Or by E-mail. 4 A. If we include E-mail, it was 5 probably more frequently than once a week, 6 although it's really hard for me to estimate. It 7 would be pretty varied. 8 Q. Who was Doctor Leigh Thompson 9 at that time? 10 A. I believe that he may have 11 undergone a couple of specific title changes, 12 actually, during this period, neither of which I 13 could quote to you verbatim. He was, as I 14 understand it, amongst other things, the 15 supervision, the management -- my management, 16 myself, Doctor Masica, Doctor Zerbe, Doctor 17 Thompson. 18 Q. He was an individual, at least 19 at that time, who had sufficient authority to 20 speak directly with the chairman of the board of 21 Eli Lilly and Company, wasn't he? 22 A. I don't know if he had to make 23 appointments or not, but he certainly spoke with 24 Mister Wood and would make presentations to Page 258 1 Mister Wood. 2 Q. Do you see there -- do you 3 remember reviewing this data? 4 A. No. As I said, I can recall 5 Doctor Thompson sending me on multiple occasions 6 sets of slides, both related to this issue and 7 not, but I can't recall any one specific set. 8 Q. Down there on the bottom of 9 the page in Doctor Heiligenstein's comments, he 10 says verbatim four: We -- and I assume he's 11 including you when he says Charles, David and I 12 reviewed your presentation. He says we feel that 13 certain caution should be exercised in a 14 statement that suicidality and hostile acts in 15 patients taking Prozac reflect the patient's 16 disorder, and not a causal relationship to PZ, 17 meaning Prozac, correct? 18 A. Correct. 19 Q. End quote. Apparently that 20 was what was quoted in the verbatim, right, or 21 verbata. 22 A. That would be an assumption on 23 my part. 24 Q. By virtue of the fact that Page 259 1 it's in quotes? 2 A. By virtue of the fact that 3 it's in quotes, yes. 4 Q. He goes on to say, 5 postmarketing reports are increasingly fuzzy, and 6 we have assigned yes, reasonably related, on 7 several reports, correct? 8 A. That's correct. 9 Q. Did you disagree with Doctor 10 Heiligenstein in making those comments? 11 A. No. 12 Q. Did you in fact have occasion 13 where you had assigned yes, reasonably related, 14 on several reports? 15 A. As I said, I cannot recall any 16 specific 1639 that I filled out. I have 17 indicated that we took a very conservative 18 approach to all adverse event reports, and 19 frequently, from a regulatory perspective, 20 assigned that. So I may well have assigned yes, 21 causality, from a regulatory perspective to a 22 Prozac report. 23 Q. Did you assign causality in a 24 suicide situation as reasonably related when you Page 260 1 didn't believe in fact medically that it was 2 reasonably related, Doctor Beasley? 3 A. There were times when -- and 4 again, I'm being hypothetical here because I 5 don't have concrete specific knowledge of a 6 particular report. There would have been 7 potentially times that I would have assigned yes 8 when I did not have any data to indicate to me 9 that there was a reasonable probability to 10 believe that it was related. 11 Q. Why would you do that? 12 A. Again, this came from a very, 13 very conservative reporting practice that had 14 been encouraged, it would have been encouraged 15 for us to take. 16 Q. There was no requirement that 17 you put reasonably related on something that you 18 don't have some medical basis for, is there? 19 A. No. 20 Q. And is that what you're saying 21 you were doing? 22 A. Yes. 23 Q. Was there a Lilly directive 24 that you assign causation to a particular suicide Page 261 1 with respect to Prozac when you didn't have any 2 medical basis for such an assignment? 3 A. If you mean by directive a 4 written policy, no, that was not the case. My 5 recollection is that we were encouraged to be, in 6 a global sense, very conservative on reporting. 7 Q. Did you take that to mean that 8 you would assign causality when there was no 9 medical basis for assigning causality, Doctor 10 Beasley? 11 A. As I explained earlier, for me 12 personally that translated into if I absolutely, 13 positively couldn't be sure that there was not an 14 association, and that would be very difficult to 15 do, I would assign possibly. 16 Q. So you're saying that your -- 17 are you paid by Eli Lilly and Company to render 18 judgment as a physician in your capacity at Eli 19 Lilly? 20 A. Yes. 21 Q. You're hired to be, because of 22 your medical training, aren't you, Doctor Beasley -- 23 A. That's my understanding. 24 Q. And I would assume were you Page 262 1 hired specifically because you were trained as a 2 psychiatrist? 3 A. That's correct. 4 Q. Now are you telling me that 5 you are assigning causality on reports of suicide 6 as being related to Prozac when you didn't have a 7 reasonable medical basis to do so? 8 A. I'm telling you I may have. 9 Q. Who would encourage you to do 10 that at Lilly, I want names? 11 A. Excuse me, I heard names, but -- 12 Q. I want names of individuals 13 who would encourage such a practice. 14 A. I recall Doctor Thompson being 15 very encouraging of being very conservative. 16 Whether he not -- he made the explicit statement 17 to be -- to assign causality under all 18 circumstances unless you were absolutely, 19 positively convinced it didn't occur, I cannot 20 recall him to make that explicit statement. 21 Q. Okay. I'm not sure I 22 understand. You say Doctor Leigh Thompson may 23 have told you to be conservative, but you're not 24 saying here that he told you to assign causality Page 263 1 in something that was in fact against your 2 medical judgment concerning the causality of the 3 reaction to the drug? 4 A. Excuse me, you just indicated 5 that it would be against my medical judgment. In 6 fact what I said is that adverse events were in 7 fact not assigned as possibly causally related if 8 I had very, very good reason to believe that they 9 weren't causal. What I have indicated is if 10 there were neutrality or there was absence of 11 information to suggest that they weren't, that 12 they were not causally related, then assign 13 causality as possible. 14 Q. And who told you to do that? 15 A. Again, I do not recall anyone 16 specifically telling me to do that. 17 Q. Have you seen an instance, 18 Doctor Beasley, where you believe in your medical 19 judgment that Prozac was the cause of a suicidal 20 act? 21 A. No. 22 Q. Have you seen an instance 23 where you, in your medical judgment, have 24 believed that an ideation was caused by ingestion Page 264 1 of Prozac? 2 A. No. 3 Q. And I mean by that suicidal 4 ideation, did you understand that? 5 A. Yes. 6 Q. And are you telling me that 7 you went according -- went contrary to your 8 medical judgment in assigning reasonably related 9 to suicidal acts and ideations anyway? 10 A. From a regulatory perspective, 11 I did. 12 Q. At whose instructions? 13 A. I can't recall anyone's 14 specific instructions. 15 Q. Are you telling me that from a 16 regulatory standpoint that you're required to 17 assign causality to a particular act when you, in 18 your medical judgment, believe otherwise? 19 A. No, that's not my 20 understanding. 21 Q. Then why were you doing so, 22 sir? 23 A. Because I believed it was 24 conservative regulatory policy. Page 265 1 Q. Who told you to do this in 2 response to conservative regulatory policy? 3 A. Again, I'm sorry, but I cannot 4 recall any specific individuals making this 5 recommendation or assignment. 6 Q. Is there some specific Lilly 7 policy in practice concerning conservative 8 regulatory action by virtue of -- as required for 9 its medical doctors? 10 A. Again, I'm not aware of any 11 written document that -- 12 Q. When was this conservative 13 regulatory practice begun by you? 14 A. I believe it was begun from 15 virtually the day that I began working on 1639s, 16 DEN reports. 17 Q. So it's your testimony that 18 when you began working on 1639s, you were 19 assigning causality to suicidal acts to Prozac 20 when you didn't believe in your medical judgment 21 that such causality existed? 22 A. I did not have data to 23 indicate that Prozac was not causally related, 24 and therefore assigned possible causality. Page 266 1 Q. Is there a difference in 2 causality, possible causality, in your opinion? 3 MR. MYERS: Let me object to the form 4 because the terminology that's been thrown about 5 is regulatory terminology defined as a matter of 6 law. 7 MR. SMITH: I'm talking about in his 8 opinion. 9 MR. MYERS: I still object to the form 10 of the question. 11 A. Could you ask the question 12 again? 13 (THE COURT REPORTER READ BACK THE 14 REQUESTED TESTIMONY.) 15 MR. MYERS: Same objection. 16 A. There would be potentially 17 definitive causality, absolutely, positively no 18 question about it, causality. I'm not sure how 19 one -- theoretically, I'm not sure how one would 20 ever determine that. I guess if you've got a 21 pneumococcal pneumonia, you've got it on gram 22 stain, pneumococcal pneumonia, there is absolute 23 absence of causality. There may well be a 24 continuum in between. What I'm saying is from a Page 267 1 regulatory perspective to complete these 1639s, 2 for any adverse event, unless I believe that I 3 had absolute definitive information to absolutely 4 categorically rule out a causality, that I would 5 assign possible causality. 6 Q. What would be absolute 7 definitive information that would rule out the 8 study drug as a particular causative agent? 9 A. Again, this, to some extent, 10 is personal opinion about how much is enough. I 11 think the sort of things that we would not -- 12 that I would not assign causality to would be 13 random events, such as patient hit by a bus while 14 walking down the street, or the -- 15 Q. Don't let me -- 16 MR. MYERS: Let him finish, Paul, and 17 then ask him, please. 18 A. Or the report of the 19 observation of a carcinoma on chest x-ray one day 20 after beginning a drug. 21 Q. We're talking about suicide 22 and suicidal ideation. So the event reported is 23 going to be suicidal ideation or some act of 24 suicide, correct, patient jumped out window, Page 268 1 patient took Drano, patient laid head down on 2 railroad tracks and let freight train run over 3 him. 4 A. Right. 5 Q. So you're going to have some 6 indication that the reporter is, by virtue of 7 making that report, concerned whether or not that 8 adverse event of suicide or suicidal ideation is 9 related to the ingestion of Prozac, right? 10 A. They may simply be reporting 11 it to us. I wouldn't presume whether or not they 12 had concerns or not unless they expressed them. 13 Q. The form is an adverse event 14 form, isn't it? 15 A. Yes. 16 Q. And it's a form that's to be 17 filled out in case the doctor experiences or has 18 a patient who is experiencing what he thinks may 19 be an adverse event with the drug, correct? 20 A. The only requirement is a 21 temporal association. 22 Q. Right. 23 A. Not causality. 24 Q. But you're not going to have a Page 269 1 situation where a patient dies from lung cancer 2 and have it reported to you that the adverse 3 event is suicide, are you? 4 A. Could you read the question 5 again, please? 6 (THE COURT REPORTER READ BACK THE 7 REQUESTED TESTIMONY.) 8 A. That would strike me as 9 impossible. 10 Q. Yes. What I'm talking about 11 is when you receive this as a clinical research 12 physician at Eli Lilly, you're assuming -- if 13 it's from a health care practitioner, you're 14 assuming that they're going to put something on 15 the 1639 that has a temporal association with the 16 drug that could in any way medically be related 17 to the use of the drug, right? 18 A. It might or might not be 19 related to the use of the drug. It clearly -- an 20 event, something that was negative that occurred 21 with or to the patient. 22 Q. If they didn't have a question 23 about it, they wouldn't be reporting it, would 24 they? Page 270 1 A. You're asking me to assume 2 what was in their mind when they reported. 3 Q. No, I'm asking you to assume 4 what's in -- you to tell me what's in your mind 5 when you receive a report. 6 A. That something bad has 7 happened to a patient. 8 Q. While on Prozac? 9 A. Correct. 10 Q. And they -- the reporting 11 health care practitioner is making you aware of 12 that fact? 13 A. That's correct. 14 Q. The health care practitioner 15 can or cannot express his opinion concerning any 16 relationship between the drug and the condition 17 complained of, correct? 18 A. That's correct. 19 Q. Now, are you telling me that 20 there are some federal requirements that require 21 you as a clinical research physician for Eli 22 Lilly reviewing 1639s that you must assign 23 causality if there's no medical excuse to rule 24 out the fact that that particular event might not Page 271 1 have been caused by the medication? 2 MR. MYERS: Object to the form, that 3 calls for a legal and regulatory conclusion. 4 Tell him if you know. 5 A. I'm not aware of any. 6 Q. Then why are you telling me 7 that -- you say that you're exercising a very 8 conservative regulatory approach in making this 9 determination to causality. I'm wanting to know 10 where it is that you get that there is some 11 regulatory requirement that you act very 12 conservatively? 13 A. Again, I'm unaware of any 14 regulatory requirement that explicitly states 15 that unless I have, in my best opinion, 16 definitive information that something is not 17 causally related, that I should make it causally 18 related. Again, I have indicated to you that I 19 believe that a position, a philosophy, if you 20 will, of being very conservative with our 21 regulatory reporting at Lilly was something very 22 much part of medical from the time that I 23 arrived. 24 Q. And has required you to make Page 272 1 assignments of causation with respect to suicide 2 and Prozac that you didn't believe from a medical 3 standpoint? 4 A. Again, I did not indicate that 5 it was a requirement, but that that was my 6 interpretation with regard to all adverse events, 7 and I did not treat suicidality any differently. 8 MR. SMITH: Okay. 9 MR. MYERS: Let's break for today. 10 Thank you. 11 (DISCUSSION OFF THE RECORD.) 12 * * * * * * * * * * 13 THE DEPOSITION WAS ADJOURNED UNTIL 14 THE FOLLOWING DAY WHEN THE PROCEEDINGS 15 CONTINUED AS FOLLOWS: 16 * * * * * * * * * * 17 18 FURTHER DIRECT EXAMINATION 19 BY MR. SMITH: 20 Q. Doctor Beasley, we are 21 beginning the second day of your deposition and 22 you understand that even though the court 23 reporter has not administered the oath today the 24 oath she administered yesterday is still in Page 273 1 effect? 2 A. Yes, I do. 3 Q. Again, let me caution you that 4 if I ask you any questions that you are unclear 5 on or don't understand, please ask me to rephrase 6 the question and I will be glad to. 7 A. Thank you. 8 Q. You understand that this 9 testimony will be presented at the trial of these 10 cases, and by virtue of that it's important that 11 we have a clear record. 12 A. Yes, I do. 13 Q. First, Doctor Beasley, I have 14 some good and bad news for you. The good news is 15 that today is the last day of this week that you 16 will be giving your deposition. We had 17 originally scheduled that you give your 18 deposition again tomorrow, but Doctor Mel 19 Perelman could only do it -- tomorrow was the 20 only day he had available and Mister Myers said 21 you would be glad to defer to Doctor Perelman. 22 A. To Doctor Perelman I think 23 that would be appropriate, yes. 24 Q. My question is do you have Page 274 1 some availability within the next thirty to 2 forty-five days that you could make yourself 3 available to complete your deposition? 4 A. I believe I do. 5 Q. You don't have a vacation 6 scheduled or intend to be out of town for any 7 extended period of time? 8 A. For the the next approximately 9 two weeks, but -- 10 Q. You will be on vacation the 11 next two weeks? 12 A. I will be at meetings. 13 Q. After that, you will be 14 generally available? 15 A. Yes. 16 Q. As I understand it, you were 17 the medical monitor of ten clinical trials 18 involving Prozac, is that right? 19 A. That was the approximate 20 number, yes. 21 Q. I would assume that in each 22 one of those ten trials, those trials were done 23 according to a protocol? 24 A. That's correct. Page 275 1 Q. And the procedure is that that 2 protocol must be approved by the Food and Drug 3 Administration? 4 A. If the study is conducted 5 under our IND, that's the case. 6 Q. All of the studies that you 7 were the medical monitor on, these approximately 8 ten studies, were conducted under the IND? 9 A. I believe that's the case, 10 yes. 11 Q. Therefore, they all had to 12 have protocols that were approved? 13 A. That's my understanding, yes. 14 Q. As did protocols with respect 15 to all of the double-blind placebo or tricyclic 16 controlled trials that were the subject of your 17 meta-analysis that you reviewed? 18 A. That's correct. 19 Q. They were all done under 20 protocols that were approved by the Food and Drug 21 Administration? 22 A. That would be my 23 understanding, yes. 24 Q. And those protocols provide Page 276 1 for how the clinical trial is to be conducted, 2 correct? 3 A. That's correct. 4 Q. And provides for the way in 5 which the results of the clinical trial are 6 transmitted back by the investigator to Lilly? 7 A. I'm -- in general terms, yes. 8 Q. Maybe not specific, because as 9 I understand it there may be separate 10 investigators' manuals, or policy and procedure 11 guides that deal with the details of this 12 transmission of this information from the 13 investigator to Lilly at Indianapolis, correct? 14 A. That's correct. 15 Q. Additionally, there are Food 16 and Drug Administration regulations with respect 17 to your dealings between Lilly and the particular 18 investigator. 19 A. I believe that's correct. 20 Q. Therefore, you have rules and 21 regulations set in place that are approved by the 22 FDA as per the protocols of the trials? 23 A. I'm not entirely certain what 24 you're asking me. Page 277 1 Q. Well, the protocols require, 2 for instance, that the investigator submit case 3 report forms on a periodic basis. 4 A. That's correct. 5 Q. And there is a requirement 6 that the case report form be filled out properly. 7 A. There is an expectation that 8 the case report form be filled out correctly. 9 Q. In fact, some of the duties of 10 the clinical research administrators and the 11 personnel, we understand it here at Lilly, are to 12 review these case report forms to ensure that 13 they are done accurately and if there is any 14 errors they get back with the investigator 15 on-site and make sure that there is a consistent 16 report. 17 A. That is as accurate as 18 possible, that's correct. 19 Q. And there are people at Lilly 20 that do that full time, that is communicate with 21 the investigator to make sure that accurate 22 information is transmitted on the case report 23 forms. 24 A. There are people that fulfill Page 278 1 that function, yes. That might not be a full 2 time exclusive duty. 3 Q. And it's part of your job as 4 the clinical monitor to in general oversee that 5 that's done. 6 A. That's correct. 7 Q. And these individuals, and you 8 as clinical monitor, also are charged with the 9 responsibility to make sure that the information 10 transmitted is transmitted as per the protocol? 11 A. Again, the protocol is quite 12 general in terms of how this information is to be 13 transmitted. It is certainly our function to 14 endeavor to see that the case report form which 15 is the transmittal instrument, in most cases, is 16 filled out correctly and accurately. 17 Q. As I understand it, in the ten 18 trials that you've done, you don't recall that 19 you've ever asked a clinical investigator his 20 opinion concerning whether or not a particular 21 suicide or suicide attempt was caused by the 22 drug? 23 A. I don't recall that, no. 24 Q. And you think generally you Page 279 1 would recall that if you had a situation where 2 that occurred? 3 A. I think I would, but again I 4 don't recall it. 5 (PLAINTIFFS' EXHIBIT NO. 7 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Would you review the document 9 that's been handed to you and marked as Exhibit 10 7, please, Doctor? 11 A. Yes, I will. 12 Q. I'm not asking that you read 13 every word, but just get yourself generally 14 familiar with what it is. I'm going to ask you 15 some specific questions about the document and I 16 will point to the page and section that I'm 17 asking. 18 MR. MYERS: Doctor, notwithstanding 19 Mister Smith's suggestion, read as much of it as 20 you feel necessary in order to be conversant and 21 to answer his questions. We'll just see how his 22 questions go. But you review it in whatever 23 level of detail you feel necessary. 24 Q. I'm just going to ask you Page 280 1 about one page of that document, Doctor Beasley. 2 Again, I don't want to limit you in familiarizing 3 yourself with it, but -- 4 A. What page would you like me to 5 review? 6 Q. Page 122, the last page. 7 A. Excuse me, my pages are not -- 8 page 122? 9 Q. It's the last page. 10 A. I've read the last page. 11 Q. Doctor Beasley, do you 12 recognize Exhibit 7 as a review and evaluation of 13 the efficacy data on Prozac (Fluoxetine 14 Hydrochloride) done by the Food and Drug 15 Administration? 16 A. I would see that that is the 17 title and it would be an assumption on my part 18 that it was authored by the FDA, but I would 19 assume so. 20 Q. Does that appear to be a 21 reasonable assumption on your part? 22 A. Yes, it does. 23 Q. Based on my representations? 24 MR. MYERS: May I just ask, because I Page 281 1 have not looked. Am I to understand that this is -- 2 at least the cover indicates that it's a review, 3 but there are certain pages included, but not the 4 entire review? 5 MR. SMITH: Yes. 6 MR. MYERS: Okay. Go ahead. 7 Q. If you turn to the first page, 8 you will see that there is a table of contents 9 that describes generally what the review contains 10 and outlines the various protocols and clinical 11 trials that were submitted by Lilly to the Food 12 and Drug Administration. 13 A. That's correct. 14 Q. And identifies particular 15 protocols and particular investigators, does it 16 not? 17 A. That's correct. 18 Q. Have you ever seen the review 19 and evaluation of efficacy data, a portion of 20 which is marked Beasley Exhibit 7? 21 A. I cannot recall seeing this, 22 no. 23 Q. It appears that it was done -- 24 well, there is a stamp on the top right-hand side Page 282 1 of the page that says NDA file, March 28th, '85 2 and then there's various submission dates down in 3 the lower left-hand corner of the page. 4 A. On this front page, yes. 5 Q. So I would assume it would be 6 March or April when this was done, correct? 7 A. Again, I can see the dates of 8 March and the last date on the bottom submission 9 being April 25, 1985. 10 Q. In any event, it appears it 11 was done prior to approval by the Food and Drug 12 Administration, does it not? 13 A. Yes. 14 Q. Turn with me to page 122. 15 A. Yes. 16 Q. And page 122 is under the 17 safety section, is it not of the review? 18 A. Yes. 19 Q. And specifically is under the 20 Item E listed on page 121 as adverse events. 21 A. Yes. 22 Q. On page 121, there is a 23 heading, Item C -- I mean 122, there is a heading 24 Item C, Method for determining the occurrence of Page 283 1 adverse events, correct? 2 A. That's correct. 3 Q. It says, A specific procedure 4 for determining the occurrence of adverse effects 5 was not provided, paren, e.g. , spontaneous 6 reporting versus systematic reporting, close 7 paren. However, since a list was not provided 8 one might assume it was similar to a spontaneous 9 reporting system. According to the protocols and 10 the case report forms, the investigator was to 11 record all adverse experiences on the case report 12 form and to assume responsibility for determining 13 the relationship of any adverse experiences to 14 the study drug, end quote. Is that correct? 15 A. That's correct. 16 Q. Now, that tells me that under 17 Lilly's protocol that Lilly required their 18 investigators to record adverse experiences that 19 occurred during the clinical trials. 20 A. That's correct. 21 Q. And also to assume 22 responsibility for determining the relationship 23 of any adverse experience to the study drug, 24 correct? Page 284 1 A. I would clearly read this to 2 indicate that that was the belief of the 3 individual who authored this, yes. 4 Q. Well, it says according to the 5 protocol and the case report forms. 6 A. And -- 7 Q. The investigator was to record 8 all adverse experiences on the case report forms 9 and to assume responsibility for determining the 10 relationship of any adverse experience to the 11 study drug. Isn't that what it says? 12 A. That's correct. 13 Q. Well, my question to you is, 14 Doctor, were your investigators doing that? 15 A. Again, this report covers 16 studies conducted at least prior to 1985, which 17 was two years before my arrival at Lilly. 18 Q. I understand. 19 MR. MYERS: Let him finish, Paul, let 20 him finish. 21 Q. You weren't finished? 22 MR. MYERS: He was getting ready to 23 say something and you interrupted. 24 A. Our case report forms for Page 285 1 studies on which I worked on did not require a 2 causality determination. 3 Q. Okay. But for your 4 meta-analysis and for your position paper for 5 Lilly on suicidality, you included protocols 6 covered by this analysis? 7 A. That's correct. 8 Q. Specifically protocol number 9 27. 10 A. That's correct. 11 Q. Is listed in the table of 12 contents, correct? 13 A. That's correct. 14 Q. And is reviewed by this Food 15 a1nd Drug Administration employee, correct? 16 A. That's correct. 17 Q. And you went back and made a 18 careful analysis of protocol number 27 and came 19 to the conclusion that that didn't support any 20 presumption that there were any -- there was any 21 link to suicide and Prozac, didn't you? 22 A. Yes. 23 Q. Well, did you go back and look 24 at the case report forms on protocol number 27? Page 286 1 A. I'm uncertain as to whether 2 that protocol was scanned electronically or 3 manually. 4 Q. Well, wasn't it reviewed in 5 one of the two forms? 6 A. Yes. 7 Q. Well, were the investigators' 8 case report forms looked at by you or somebody at 9 Lilly? 10 A. Yes. 11 Q. Didn't somebody look at these 12 case report forms when there would be an adverse 13 event recorded and see what the investigator had 14 said in connection with determining the 15 relationship of a particular adverse experience 16 to the study drug? 17 A. I cannot answer with regard to 18 what anyone might have done at any point in time. 19 I certainly did not. 20 Q. Why wasn't that data, that 21 information that was supposed to be on the case 22 report form mentioned by you in your paper, 23 Doctor Beasley? 24 A. Because the paper was a count Page 287 1 of events occurring, suicidal acts and changes in 2 the Hamilton Item 4. That was the methodology 3 that was established, it was fully discussed in 4 the paper. That was the methodology that was 5 established. 6 Q. You don't discuss in your 7 paper that according to the protocols of the 8 clinical trial that you reviewed and reported on 9 that there was information supposedly held by 10 Lilly concerning what their investigator's 11 opinion was with respect to whether or not the 12 adverse event, i.e. suicide or suicide attempt, 13 was related to the study drug, Prozac? 14 MR. MYERS: Object to the form, 15 assumes facts that are not in evidence. Go ahead 16 and answer, Doctor. 17 A. I would agree with you. 18 Q. Wouldn't you agree with me 19 that that would be relevant information for 20 medical doctors to know in connection with making 21 a decision with respect to whether or not to 22 prescribe this medication? 23 A. It might be a component of 24 information that would be important in a review Page 288 1 of the issue of the relationship of the drug to 2 suicidality, all information that's available is 3 important. 4 Q. But you didn't put that in 5 your paper -- 6 A. No. 7 Q. -- did you? Do you know of 8 any reason why physicians in this country 9 shouldn't know what Lilly's investigators thought 10 about whether or not suicide was in any way 11 related to Prozac? 12 MR. MYERS: Same objection as to form. 13 Go ahead and answer. 14 A. I don't know of any reason. 15 Q. Did you know, Doctor Beasley, 16 at the time you made your meta-analysis that you 17 had information on the case report forms 18 themselves that would indicate what the 19 investigator's opinion was concerning whether or 20 not Prozac was responsible or related to the 21 patient's use of Prozac -- was related to the 22 patient's suicide or suicide attempt? 23 MR. MYERS: Same objection as to form. 24 A. I don't recall knowing that, Page 289 1 no. 2 Q. Wouldn't that be information 3 that would be relevant to the issue at hand, 4 Doctor Beasley? 5 A. It might be. 6 Q. Well, it is, isn't it? 7 MR. MYERS: Let me object to the 8 question. He's answered it on two separate 9 occasions. Answer it one more time, Doctor, go 10 ahead. 11 A. It might be. 12 Q. You're not going to say that 13 it is relevant, only that it might be relevant? 14 A. That's correct. 15 Q. Well, is it as relevant as 16 statistical data? 17 A. Again, my belief is that the 18 statistical data is a more important component 19 and a more objective component of the data. 20 Q. Do you think that your 21 investigators were not being objective in making 22 this required determination with respect to 23 whether or not the adverse event of suicide or 24 suicidality was related to the drug? Page 290 1 A. I have no way of assessing the 2 validity of that assessment. 3 Q. Why don't you call them on the 4 phone and ask them? 5 A. Again, I have no way of 6 assessing the validity of that assessment. 7 Q. They could tell you what basis 8 they made that determination on, couldn't they, 9 if you asked them? 10 A. They might. 11 Q. Have you had any instance 12 where an investigator hired by you or hired by 13 Eli Lilly and Company refused to give you 14 information that you requested of them? 15 A. No. 16 Q. Have you had any instance 17 where you were of the opinion that the 18 investigator was not being completely 19 straightforward with you with respect to what he 20 was reporting to you on case report forms? 21 A. An investigator, no. 22 Q. Don't you look to the 23 investigator's integrity when you select an 24 investigator to do a study? Page 291 1 A. Yes. 2 Q. As well as his educational 3 training and background? 4 A. Yes. 5 Q. As well as his competence as a 6 psychiatrist? 7 A. Yes. 8 Q. And as well as his competence 9 to observe adverse events occurring in the 10 subject patients? 11 A. Yes, to observe events. 12 Q. And as well as his ability to 13 report those events to you? 14 A. It's very important that he 15 does report those events that he observes. 16 Q. Are you able, as a physician, 17 Doctor Beasley, to make diagnosis on patients you 18 haven't examined? 19 A. On patients that I have not 20 examined? 21 Q. Yes. 22 A. No, that would be 23 inappropriate. 24 Q. Can you tell me what my Page 292 1 physical condition is simply by the one day and 2 one hour that we've spent together? 3 A. No, sir. 4 Q. You don't know if I have any 5 underlying condition, do you? 6 A. No, sir. 7 Q. Isn't it -- aren't you taught 8 in medical school that the most valid assessment 9 of a physical or psychiatric condition is that 10 assessment made by a trained physician who has 11 examined and observed the patient? 12 A. Could you restate the question 13 once more? 14 (QUESTION READ.) 15 A. If we are referring to 16 reporting of observed phenomena or diagnosis, 17 yes. 18 Q. All right. In fact, Doctor 19 Beasley, these investigators conducting these 20 trials had more actual hands-on experience in 21 treating patients with mental disorders than you? 22 A. That's correct. 23 Q. And by all the clinical 24 research physicians involved in this analysis? Page 293 1 MR. MYERS: When you say this 2 analysis, do you mean this or this paper? 3 Q. This analysis reflected by 4 your paper. 5 A. I can't really speak to the 6 details of my colleagues' extent of clinical 7 experience. 8 Q. Well, you know your 9 investigators had more clinical experience than 10 Doctor John H. Heiligenstein, don't you? 11 A. Doctor Heiligenstein was the 12 one specific one that came to my mind who has 13 more extensive clinical experience. 14 Q. Than you? 15 A. Absolutely. 16 Q. But he doesn't have more 17 extensive clinical experience than any of your 18 investigators, does he? 19 A. Again, it would be speculative 20 for me to answer that. 21 Q. How about the ten 22 investigators that were conducting the studies 23 that you were the medical monitor of? 24 A. I'm sorry, but I don't know Page 294 1 the number of years of Doctor Heiligenstein's 2 clinical practice. I think it was rather 3 significant, but I'm not certain how many years 4 that was. 5 Q. About five. 6 MR. MYERS: I object to the form. You 7 mischaracterized Doctor Heiligenstein's 8 testimony. 9 MR. SMITH: Well, then you tell him. 10 I'll accept what you say. 11 MR. MYERS: I'm not going to tell him 12 anything. He said he doesn't know. 13 MR. SMITH: I don't want to 14 mischaracterize experience. If you say I 15 mischaracterized his experience, I'll take your 16 representation -- 17 MR. MYERS: It's not my -- 18 MR. SMITH: -- to ask him the 19 questions. 20 MR. MYERS: It's not my responsibility 21 to frame the question, Mister Smith. He said he 22 didn't know. Go on to something else or somebody 23 else. 24 Q. How about Doctor Bruce Page 295 1 Dornseif? 2 MR. MYERS: I object to form. He's 3 not a physician. 4 MR. SMITH: That's right, so certainly 5 your investigator's got more experience in 6 observing this then, the psychiatric phenomena, 7 than somebody who's not a physician such as 8 Doctor Dornseif, right? 9 A. Excuse me, yes. 10 Q. Doctor Dornseif is a 11 statistician, isn't he? 12 A. Yes, absolutely. 13 Q. Ms. Bosomworth, one of the 14 other co-authors on your paper, is not a medical 15 doctor, correct? 16 A. That's correct. 17 Q. Nor is Mary E. Saylor. 18 A. That's correct. 19 Q. Nor is Alvin H. Rampey, 20 Junior. 21 A. That's correct. 22 Q. Nor is Vicki Thompson. 23 A. That's correct. 24 Q. Nor is David Murphy -- or is Page 296 1 he? I don't know who David Murphy is. 2 A. No. 3 Q. Who is David Murphy? 4 A. David is the systems person 5 that was involved. 6 Q. Beg your pardon? 7 A. The systems analyst. 8 Q. He is a computer operator. 9 A. That's correct. 10 Q. And Doctor Masica is listed as 11 a co-author. 12 A. That's correct. 13 Q. How many years of clinical 14 experience outside of Lilly does Doctor Masica 15 have? 16 A. I don't know the number. 17 Q. Limited, isn't it? 18 A. I'm sorry, I don't know the 19 number. 20 Q. We can say, can't we, Doctor 21 Beasley, that of the three authors on this paper, 22 you have had less clinical experience in treating 23 patients with psychiatric disorders, can't we? 24 A. Oh, absolutely. Page 297 1 (PLAINTIFFS' EXHIBIT NO. 8 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. You probably better read both 5 pages of this, Doctor Beasley. 6 A. I have finished reading. 7 Q. Have you seen Exhibit 8 8 before, Doctor Beasley? 9 A. I believe that I have, yes. 10 Q. Was this part of the materials 11 that you were asked to review in preparation for 12 your deposition? 13 MR. MYERS: If you reviewed it, tell 14 him. 15 A. I can't recall seeing this one 16 specifically, I may have. 17 Q. When did you review materials 18 in preparation for your deposition? 19 A. There were two or three days 20 of conversation with counsel approximately a 21 month ago. I did so on Thursday of last week and 22 Monday of this week. 23 Q. Do I understand that you had 24 conferences with your attorneys on Thursday and Page 298 1 Monday? 2 A. Thursday of last week and 3 Monday of this week. 4 Q. And did you review documents 5 in addition to discussing the case with your 6 attorneys? 7 A. I did not look physically at 8 documents. 9 Q. Did you ever review documents 10 in preparation for your deposition? 11 A. I, on one occasion, reviewed 12 several articles that I had prepared or 13 co-authored including the suicidality article. 14 I, in fact, I believe delivered them to my 15 attorneys. 16 Q. But other than that, have you 17 looked at a stack of documents? 18 A. No. 19 Q. To prepare yourself for this 20 deposition? 21 A. No. 22 Q. Or in any way help you recall 23 facts that occurred over a period of time? 24 A. No. Page 299 1 Q. Why was it then that you 2 looked at Mister Myers when I asked you if you 3 had reviewed this Leber article? 4 MR. MYERS: Don't answer that, don't 5 answer that question. Go ahead and ask him a 6 question about something of substance, Paul. He 7 told you what he reviewed. 8 Q. I thought you said earlier 9 that you had reviewed the Leber memo? 10 MR. MYERS: He didn't say that. I 11 object to the form. 12 MS. ZETTLER: What he said was he 13 wasn't sure if he did or not, Larry. 14 MR. MYERS: And he answered the 15 question as to what it was that he did review in 16 response to a direct question from you, Mister 17 Smith. 18 Q. Have you reviewed the Leber 19 memo? 20 A. I have not seen this memo 21 physically in the preparation. I may have heard 22 about this memo from counsel in preparation. I 23 have not physically had the opportunity to read 24 this. Page 300 1 Q. All you've heard is it's been 2 characterized by counsel, but they've not 3 provided you -- 4 A. With a copy. 5 Q. -- with an actual copy of that 6 document? 7 A. That's correct. 8 Q. In reading the document, does 9 that in any way affect your impression of what it 10 was described to you? 11 MR. MYERS: Let me caution you, Doctor 12 Beasley, do not disclose anything in answering 13 any of Mister Smith's questions that you 14 discussed with counsel. 15 MR. SMITH: I didn't ask him that. 16 MR. MYERS: I understand that, I'm 17 just cautioning him. 18 A. Could you please repeat the 19 question? 20 (QUESTION READ) 21 A. I'd like to first try to 22 restate my understanding of the question to make 23 sure I'm clear. Is that okay? 24 Q. That would be fine. I'm glad Page 301 1 you're doing that, that's an example of instances 2 where I want you to tell me if you're uncertain 3 of my question. And you're doing that, so I'm 4 proud of you. 5 A. Thank you. I want to make 6 real sure I understand. You're asking me, now 7 that I have read this, does it give me any 8 different impression of the contents of the 9 document than I had when I believe it was 10 reviewed with me with counsel? 11 Q. Exactly. 12 A. No. 13 Q. Did you ask to review the 14 Leber document? 15 A. No. 16 Q. Have you asked that any 17 documents be provided to you to assist you in 18 giving your deposition -- 19 A. No. 20 Q. -- here today. Of course you 21 are an individual who was apparently given a copy 22 of Exhibit 8, this Leber memo as we called it, 23 back when it was generated, back in July of 1990. 24 A. And that was my reference to Page 302 1 seeing it previously because I see my name 2 appearing as a recipient. 3 Q. Do you recall receiving this 4 memo, Doctor Beasley? 5 A. I don't recall sitting here 6 today specifically receiving this memo. 7 Q. Do you make it a general 8 practice to review E-mail messages of which 9 you're a recipient? 10 A. In general, yes. 11 Q. Well, how about specifically 12 an E-mail from Doctor Leigh Thompson? 13 A. Yes. 14 Q. Because he is one of your, for 15 want of a better term, bosses, is he not? 16 A. That's correct. 17 Q. In other words, if Doctor 18 Leigh Thompson asked you to do something, you 19 would accomodate him, would you not? 20 A. In general. 21 Q. Well, there were instances in 22 connection with this issue that these lawsuits 23 are about where Doctor Thompson asked you to do 24 things and you complied. Page 303 1 A. That's correct. If I may, 2 apparently this message was forwarded to me from 3 someone else, given the nature of how it is put 4 together here. 5 Q. I understand that. It wasn't -- 6 the message wasn't directed to you, it was 7 directed to, for instance, Doctor Mel Perelman, 8 who was at that time the President of Lilly 9 Research Labs, was he not? 10 A. That's correct. 11 Q. And yet you were included as 12 an individual that Doctor Thompson wanted to see 13 this memo, correct? 14 MR. MYERS: Are you asking if Thompson 15 wanted him to see it or if Thompson was the one 16 who forwarded it to him? 17 MR. SMITH: Either one, take your 18 choice. 19 MR. MYERS: Okay. Tell him if you 20 know the answer to either of those questions. 21 A. First question, being whether 22 Thompson wanted me to see it. I don't know. I 23 certainly, from my understanding of this, was not 24 the person he sent it to, I was not on the Page 304 1 original addressee list. In terms of whether he 2 sent it to me or not, again, I'm not sure who did 3 the forwarding. He could have further forwarded 4 it or not, I don't know. It could have been 5 forwarded by somebody else. 6 Q. Under that top third of the 7 page, it says, Comments: FYI to keep all -- to 8 keep you all -- apparently whoever it was that 9 typed this, had never been to Texas because he 10 says to keep you all up to date. 11 A. He should have had an 12 apostrophe and just the L-L. 13 Q. That's right. Who would have 14 directed that comment? 15 A. Again, I don't -- it would 16 have been someone I would presume from the lower 17 list of addressees. 18 Q. All right. But you don't 19 recall, as we sit here today, a specific 20 recollection of seeing this memo? 21 A. I can't recall specifically on 22 the date that this was sent to me which looks 23 like July 18th, 1990. 24 Q. The memo speaks for itself, of Page 305 1 course, but it's about generally a conversation 2 that Doctor Leigh Thompson with Eli Lilly and 3 Company has had with Doctor Paul Leber and Doctor 4 Tom Laughren of the Food and Drug Administration, 5 does it not? 6 A. Yes. 7 Q. And the conversation that they 8 had at that early 6:15 morning conference was 9 concerning suicide, was it not? 10 A. Yes, it was, according to 11 this. 12 Q. Did you -- were you generally 13 on duty at 6:15 a.m. in the morning at Lilly? 14 A. Not generally. 15 Q. Do you know of anybody at 16 Lilly that's generally at work at 6:15 a.m.? 17 A. Doctor Thompson may be quite 18 frequently. 19 Q. Does he never sleep? 20 A. Excuse me? 21 Q. Or does he sleep rarely? 22 A. He has lots of energy. 23 Q. The memo indicates that Doctor 24 Thompson is relating that they, which would be Page 306 1 Paul Leber and Tom Laughren, feel some data are 2 required and wanted a study or studies of the 3 issue, correct? 4 A. That's what I read from this 5 sentence, yes. 6 Q. And that Paul, which would be 7 Doctor Leber, suggested several designs, correct? 8 A. That's correct. 9 Q. Number one, he at the Food and 10 Drug Administration had suggested a case 11 controlled retrospective study before Teicher 12 seeing what the frequency is of patients 13 developing the Teicher syndrome. Paul felt that 14 the instrument should be developed in concert 15 with Teicher because only Teicher knows what he 16 is seeing. Correct? 17 A. That's a correct statement. 18 Q. Was there a case controlled 19 retrospective done with -- in concert with Doctor 20 Martin Teicher? 21 A. No, there was not. 22 Q. Now, you have told me about 23 what I had assumed was your first meeting with 24 Doctor Teicher at McLane Hospital, correct, Page 307 1 yesterday? 2 A. That's correct. 3 Q. Now, did you have any other 4 meetings with Doctor Teicher? 5 A. I had one additional meeting 6 if you could refer to it as a meeting. There was 7 a study group at the American College of 8 Psychopharmacology conducted two years ago in 9 which both I and Doctor Teicher spoke. 10 Q. Did you and Doctor Teicher 11 discuss this issue, the relationship of Prozac to 12 suicide and aggressive behavior? 13 A. That was the subject of the -- 14 Q. Entire workshop. 15 A. -- entire workshop. 16 Q. Did you present a paper? 17 A. An oral presentation, yes. 18 Q. Was that oral presentation 19 based on your meta-analysis? 20 A. It was based on that plus the 21 European data. 22 Q. And did Doctor Teicher 23 participate in making presentations at that 24 conference? Page 308 1 A. Yes, he did. 2 Q. What did he say concerning 3 this issue? 4 A. I don't recall the specifics. 5 As I recall he presented his cases and reviewed 6 potential etiologies. 7 Q. Was Doctor Teicher -- did 8 Doctor Teicher still hold the opinions that he 9 had expressed in his article of February of 1990? 10 A. I believe he did, yes. 11 Q. Any other conversations that 12 you have had with Doctor Teicher? 13 A. I don't believe so. We 14 endeavored to follow-up on additional information 15 with him. I do not believe I was the physician 16 that tried to make contact with him or had 17 contact with him. 18 Q. Who did? 19 A. I believe that would have been 20 either Doctor Wheadon or Doctor Heiligenstein. 21 Q. You said they tried to follow 22 up to secure additional information. How did 23 they try to follow up and what additional 24 information were they seeking? Page 309 1 A. By telephone. I don't think 2 that anyone attempted to physically visit him. 3 Doctor Teicher, as I recall, had reported some 4 additional cases or additional information 5 available on the initial cases that he had 6 reported in his article. Efforts were made to 7 follow-up on that. 8 Q. And did Doctor Teicher refuse 9 to give that additional information? 10 A. Again, since I was not the -- 11 I was not the individual that actually made the 12 contact. My recollection is that an impression 13 was conveyed to me that he was less than totally 14 cooperative. 15 Q. What do you mean by less than 16 totally cooperative? 17 A. Again, having not been a 18 specific party to the conversation, as I recall, 19 I have no specific information that I can relate 20 past that. 21 Q. Is it your testimony here, 22 Doctor Beasley, that you or Eli Lilly has 23 requested further conversation -- conversations 24 with Doctor Teicher concerning this issue and Page 310 1 that Doctor Teicher has refused to cooperate with 2 you in making an analysis of this issue? 3 A. It was not an analysis of this 4 issue, it was -- 5 Q. Discuss this issue in any 6 manner. 7 A. Specific cases and what I'm 8 saying is that may be the case. 9 Q. It may be the case. What 10 leads you to believe it may be the case? 11 A. Again that's my recollection. 12 Q. Based on what? 13 A. It's my recollection of 14 attempts that one of two clinical physicians -- 15 clinical research physicians made. 16 Q. And that would have been 17 Heiligenstein and who? 18 A. Or Wheadon. 19 Q. Or Wheadon. You didn't find 20 Doctor Teicher uncooperative when you went to 21 McLane Hospital in Boston and talked to him, did 22 you? 23 A. No. 24 Q. Quite the contrary, you found Page 311 1 him absolutely candid and cooperative with you, 2 didn't you? 3 A. That was certainly my 4 impression during my meeting. 5 Q. And at that time he never 6 refused to do anything or answer any of your 7 questions, did he? 8 A. Absolutely not. 9 Q. He was totally forthcoming 10 with you, wasn't he? 11 A. Absolutely. 12 Q. And he seemed genuinely 13 concerned about the issues? 14 A. Absolutely. 15 Q. And he seemed open to any 16 suggestions that you all might have too, didn't 17 he? 18 A. I'm -- your question implies 19 that -- 20 Q. That you made suggestions? 21 A. That we made suggestions. 22 Q. Okay. I didn't mean to imply 23 that. Did you not make any suggestions 24 concerning what might be done to further explore Page 312 1 this issue? 2 A. My recollection is that we 3 showed him data and suggested that we would be 4 doing more analyses. We didn't get specific 5 about what those would be. I did not find him to 6 be in any way unhelpful or uncooperative or make 7 any suggestion that that would not be 8 appropriate. 9 Q. And did you ask him to help 10 you in that further analysis? 11 A. That was left as an open 12 issue. 13 Q. Okay. And so did he leave it 14 open that he would be willing to help you with 15 that analysis? 16 A. That's my recollection. 17 Q. So you have no knowledge from 18 anything you personally know of any failure of 19 Doctor Teicher to cooperate with you? 20 A. From my perspective, no. 21 Q. And on the contrary, as far as 22 your meeting with him, he seemed quite 23 cooperative? 24 A. Absolutely. Page 313 1 Q. All right. Was there a case 2 control retrospective study done in cohort with 3 Doctor Teicher? 4 A. No. 5 Q. Why? 6 A. I have certainly 7 participated -- I'm uncertain. 8 Q. Okay. So am I correct that 9 your testimony would be I don't know why there 10 wasn't a case control retrospective study done in 11 cohort with Doctor Teicher? 12 A. I'm uncertain, that's correct. 13 Q. Well, are you saying you don't 14 know or you're uncertain? 15 A. I don't know. 16 Q. All right. You don't know 17 that -- you don't know why a retrospective case 18 control study wasn't done in cohort with Doctor 19 Teicher? 20 A. That's correct. 21 Q. It appears from this memo 22 that, in addition, Doctor Paul Leber of the Food 23 and Drug Administration suggested a cohort study. 24 The power is low, but if the incidence is three Page 314 1 point five percent, even a small study 2 should be able to establish relative rates 3 between Fluoxetine and other treatments. Also it 4 should set an upper limit on the incidence of 5 emergence of suicidal ideation. Correct? 6 A. That's correct. 7 Q. Was there a cohort study done? 8 A. No. 9 Q. Why? 10 A. I don't know. 11 Q. Finally, Doctor Leber with the 12 Food and Drug Administration apparently also 13 suggested to Doctor Leigh Thompson of Eli Lilly 14 and Company that, quote, best would be a larger 15 blind prospective study designed with the help of 16 Teicher to detect his phenomena. Correct? 17 A. That's correct. 18 Q. Was there a larger blind 19 prospective study done? 20 A. No. 21 Q. Was there a larger blind 22 prospective study done with the help of Teicher? 23 A. No. 24 Q. Neither type of larger blind Page 315 1 prospective study was done, was it? 2 A. No. 3 Q. Why? 4 A. I don't know. 5 Q. Do you know who would know the 6 answer to these questions? 7 A. I would presume that it would 8 be the medical management responsible. 9 Q. Who was the medical management 10 responsible for doing an investigation into the 11 issue with respect to whether or not Prozac was 12 related to suicide or violence and aggression? 13 A. It would have been Doctors 14 Masica and later Tollefson, Doctor Zerbe, Doctor 15 Thompson potentially. 16 Q. Isn't it correct, Doctor 17 Beasley, that one or all of these individuals 18 assigned to you at least in part the 19 responsibility or an assignment in connection 20 with this issue? 21 A. Which issue specifically, 22 suicidality? 23 Q. Yes. 24 A. As a general issue, yes. Page 316 1 Q. Did you feel resposible for 2 that? 3 A. For the activities that I 4 undertook on suicidality, absolutely. 5 Q. In finding an answer to this 6 question? 7 A. Yes, I did. 8 Q. And yet you never asked that 9 question to any of the investigators that 10 reported such a phenomena? 11 A. That's correct. 12 (A SHORT BREAK WAS TAKEN.) 13 (PLAINTIFFS' EXHIBITS NO. 9 AND 14 10 WERE MARKED FOR IDENTIFICATION 15 AND RECEIVED IN EVIDENCE.) 16 Q. Doctor Beasley, have you had 17 an opportunity to review Exhibits 9 and 10? 18 A. Yes, I have. 19 Q. Exhibit 9 appears to be a memo 20 that you authored? 21 A. That's correct. 22 Q. And that has to do with a 23 meeting in connection with a rechallenge 24 protocol, does it not? Page 317 1 A. That's correct. 2 Q. And were you responsible for 3 drafting the rechallenge protocol, Doctor 4 Beasley? 5 A. This was a potential study 6 that I was very much involved in, yes. 7 Q. Were you -- 8 A. The clinical research 9 physician assigned. 10 Q. All right. Would you have 11 been the medical monitor, you think, on this 12 project? 13 A. Yes, if it had come or would 14 come to pass, possibly. 15 Q. You would have been the 16 individual that would have served as the medical 17 monitor? 18 A. I would believe so. 19 Q. In Exhibit 9 is dated April 20 17th, 1991 and it's just a notice that you were 21 going to have a meeting to discuss the protocol. 22 A. That's correct. 23 Q. And in addition to employees 24 of Eli Lilly and Company, there were going to be Page 318 1 some outside consultants who were going to be 2 there that were going to help you with this. 3 A. That's correct. 4 Q. Who were those outside 5 consultants who were going to help you with this, 6 Doctor Beasley? 7 A. Unfortunately, this is blacked 8 out so I'm -- for this specific meeting, I don't 9 recall. I would presume that Doctor Miller of 10 Brown University was one of our primary 11 consultants in this area. He is a Ph.D. He also 12 had a M.D. clinician associate whose name I don't 13 recall who worked with us as well. 14 Q. Well, this meeting was going 15 to be on May 2nd, 1991. Do you think that Doctor 16 Miller and his M.D. associate were the 17 individuals who were going to be at that meeting? 18 A. I would believe that it was 19 highly likely that they were. Whether there was 20 an additional individual or not, I'm uncertain 21 about. 22 Q. Whether there was an 23 additional individual there or not, who would 24 that have been? Page 319 1 A. I don't know who that would 2 have been. 3 MR. SMITH: Can we get this 4 unredacted, please? 5 MR. MYERS: Yes. 6 MR. SMITH: Do you know who they are? 7 MR. MYERS: I don't know. 8 Q. Did you recall the subject of -- 9 the substance of that meeting? 10 A. Not that specific meeting. 11 Q. All right. Do you recall 12 anything about that particular meeting? 13 A. That specific meeting, no. 14 Q. I assume there were a number 15 of meetings -- 16 A. That's correct. 17 Q. -- in which there were 18 individuals at Lilly present and in a number of 19 meetings in which there were Lilly physicians as 20 well as outside consultants? 21 A. That's correct. 22 Q. Do you remember when your 23 first meeting was? 24 MR. MYERS: On the subject or with Page 320 1 presumably with Doctor Miller? 2 MR. SMITH: No, on the subject of a 3 rechallenge protocol. Whether it be just a 4 meeting called by Lilly, within Lilly, or a 5 meeting where you called in outside consultants. 6 A. No, I don't. 7 Q. Do you recall whether or not 8 there would have been meetings before this May 9 2nd, 1991 meeting? 10 A. Yes, I believe there would 11 have been. 12 Q. Can you give me approximately 13 months, weeks, with respect to -- prior to this 14 May meeting it would have been when you first 15 met? 16 A. To discuss a rechallenge 17 protocol? 18 Q. Yes. 19 A. I would very strongly believe 20 it would have been in the order of months. 21 Q. Well, would there have been 22 meetings in 1990? 23 A. There may have been. 24 Q. This Exhibit 8, the E-mail Page 321 1 description of a conversation between Doctor 2 Leber and Doctor Leigh Thompson at Lilly, were 3 there any discussions of a rechallenge protocol 4 prior to July 18th, 1990, when this conversation 5 occurred? 6 A. I do not recall whether there 7 were or not. 8 Q. More than likely there would 9 not have been? 10 A. That would be speculative on 11 my part. 12 Q. It is correct, Doctor Beasley, 13 that the impetus for a rechallenge protocol came 14 from the Food and Drug Administration, not from 15 Lilly? 16 A. They, the Food and Drug 17 Administration, as implied in this memo certainly 18 discussed the potential need to do a study. 19 Clearly here, as an example, there are three 20 types of designs that have been suggested. None 21 of these are rechallenge. So I think it would be 22 fair to say that there was some impetus for a 23 study at some point suggested by the FDA. 24 Specific rechallenge study, it would be less Page 322 1 clear that the impetus specifically for that came 2 from the FDA. 3 Q. All right. I think we're 4 going to go over some additional exhibits that 5 indicate that the suggestion for a rechallenge 6 study, in particular, was originated at the FDA 7 and not at Lilly. 8 A. Okay. 9 Q. Will you accept that? 10 MR. MYERS: Accept that it's a fact or 11 accept it in going over some exhibits? 12 Q. Will you accept that as a 13 fact? 14 A. Again, I cannot recall where 15 the original idea developed. 16 Q. All right. Let's go to -- 17 well, do you remember whether a draft of a 18 rechallenge protocol had actually been prepared 19 prior to May 2nd, 1991? 20 A. Prior to May 2nd? I don't 21 recall. 22 Q. What is Exhibit 10? 23 A. It appears to be some notes. 24 Q. Is that your handwriting? Page 323 1 A. That's not my handwriting. 2 Whose handwriting, I don't recognize without a 3 name attached to it. That discusses suicidal 4 ideation, suicide attempts, complete or some very 5 brief information, then goes on to discuss 6 scales, ways of rating suicidal ideation, goes on 7 to discuss particular additions to the Miller 8 scale as modified from the Beck scale, which 9 would be relevant to what Doctor Teicher had 10 reported, and then makes comments on doing a 11 pilot study of validity and liability with a 12 modified scale. 13 Q. There never was a pilot study 14 done either, was there? 15 A. Actually there is one ongoing. 16 Q. All right. Who's doing that? 17 A. Doctor Miller has completed 18 the work with his patients and the trial data are 19 being analyzed. 20 Q. Is he doing that for Lilly? 21 A. He was doing that for Lilly. 22 Q. And that's a pilot study for 23 what purpose? 24 A. To look at a modification of Page 324 1 his scale. 2 Q. To modify a suicidal ideation 3 scale? 4 A. That's correct. 5 Q. Would it be to modify it or 6 validate his suicidal ideation scale? 7 A. Well, the modifications had, 8 in fact, been made -- additional questions had 9 been added to the scale. 10 Q. Okay. We've seen the term 11 MSSI dash R, is that -- 12 A. That's correct. 13 Q. Is that what you're speaking 14 about -- 15 A. That's correct. 16 Q. -- when you say there is 17 modifications that had already occurred? 18 A. That's correct, questions had 19 been added. 20 Q. So now is it that scale that 21 is being validated by Doctor Miller in this study 22 that's just been completed? 23 A. Again, I would characterize 24 this as a pilot to look at methodology for, in a Page 325 1 more comprehensive fashion, assessing the 2 validity of that scale. 3 Q. Were individuals given 4 Fluoxetine-Prozac on that pilot study? 5 A. Not as part of the protocol. 6 Patients who were entered into the trial may or 7 may not have received Fluoxetine or any other 8 antidepressant therapy during the process of 9 looking at the scale and its rating of suicidal 10 ideation. 11 Q. Well, were there patients who 12 were randomized to Prozac? 13 A. No. 14 Q. But there were patients within 15 the study that happened to be taking Prozac? 16 A. There may have been. 17 Q. All right. But that Prozac 18 wasn't administered to them as part of the study? 19 A. No, the study was -- no. 20 Q. The study was to validate this 21 suicidal ideation scale? 22 A. Again, it was to serve as a 23 pilot in that process. 24 Q. All right. What is -- maybe Page 326 1 we should stop here and have you describe what a 2 pilot is. 3 A. A pilot as I would 4 characterize it is a relatively speaking, 5 compared to a non-pilot, smaller scale study, 6 well, lesser numbers of patients, to take a first 7 look at issues of, in this case, reliability and 8 validity of the scale, but to also take a look at 9 the feasibility of performing the larger study. 10 Q. Is the only difference in a 11 pilot study and a formal full scale study the 12 number of subjects? 13 A. The pilot could result in 14 other methodologic changes in the larger study. 15 Again, they're both formal studies. 16 Q. Was this a pilot study that 17 was submitted to the Food and Drug Administration 18 for approval? 19 A. Given that it was not a study 20 of a drug, I'm uncertain as to whether it was 21 submitted under any IND. 22 Q. Obviously, if any adverse 23 events occurred during that study, and Prozac was 24 involved, that would have to be reported, would Page 327 1 it not? 2 A. That would be correct. These 3 would be not trials, not adverse events connected 4 with Prozac as a clinical trial agent, but in the 5 domain of spontaneous events, I would think. 6 Q. Which should be picked up by 7 the DEN system? 8 A. I would believe that would be 9 the case. 10 Q. Were you the medical monitor 11 on this study? 12 A. Yes, I was. 13 Q. Were there any attempted 14 suicides in this study? 15 A. I don't recall. 16 Q. Do you think there were or 17 weren't? 18 A. I don't believe that there 19 were, but I don't recall precisely. 20 Q. Did the study pick up any 21 increased suicidal ideation on patients taking 22 Prozac? 23 A. I don't know. 24 Q. Wouldn't that be something you Page 328 1 would want to know? 2 A. Again, I am uncertain if any 3 patients in the study were receiving Fluoxetine. 4 It wasn't a requirement. I would hope that any 5 patients who did have suicidal ideation increase 6 in the study who were on Fluoxetine would be 7 brought to my attention by the investigator. 8 Q. Do you recall any such 9 instances? 10 A. No, I do not. 11 Q. Doctor Miller was the 12 investigator? 13 A. Doctor Miller and his M.D. 14 colleague. 15 Q. Who was that? 16 A. Again -- 17 Q. Oh, that's right, you don't 18 recall who that is. 19 A. Right. 20 Q. Based on the pilot study, is 21 there going to be an additional study done? 22 A. I am unaware of any specific 23 plans to conduct such a study at this time. 24 Q. What are your recommendations Page 329 1 as the medical monitor in connection with whether 2 or not to conduct a formal study? 3 MR. MYERS: Let me object to the form 4 and the use of the term "formal study" because he 5 said they were both formal studies. 6 Q. A more extensive study, in 7 addition to the pilot study that's been done. 8 A. I have yet to see the results 9 of the pilot study, and I think any 10 recommendation that I would make would require 11 that I first see the results of those data. 12 Q. Haven't you been reviewing the 13 data as part of your functions as the medical 14 monitor on the trial, Doctor Beasley? 15 A. Again, this is a trial to look 16 at the potential to assess the validity and the 17 reliability of the scale. That involves 18 statistical analyses which have not been 19 completed yet. 20 Q. But aren't you aware generally 21 of the results of that pilot study because you're 22 the medical monitor? 23 A. Yes, I am aware that patients 24 have gone through the study, but given that what Page 330 1 we're looking for as outcomes are a variety of 2 statistical parameters to assess, again, 3 reliabiltiy and validity, I don't know what those 4 will show. 5 Q. What is your impression based 6 on the information that you have? 7 A. I'm sorry, but I don't have an 8 opinion at this point in time. 9 Q. Does this study have a -- was 10 this study funded by Eli Lilly and Company? 11 A. Yes, it was. 12 Q. And does this study have a 13 S001 or S002 designation? 14 A. Yes, it does. 15 Q. Which? 16 A. I'm not certain which. 17 Q. Well, Doctor Beasley, was 18 Catherine Mesner the clinical research 19 administrator on this study? 20 A. I believe she was. 21 Q. Her testimony has been that a 22 patient committed suicide on this study. Are you 23 aware of that, that a patient -- does that help 24 you in your recollection concerning whether or Page 331 1 not any patients have committed suicide on this 2 study? 3 A. I would want to verify that. 4 Q. Do you want to call her at 5 lunch to see what you can find out about that? 6 A. I would want to verify that in 7 the case report form data. 8 Q. Well, you won't take Ms. 9 Mesner's word for it? 10 MR. MYERS: Let me object to form, 11 Paul. You told him that, he said he wanted to 12 verify it. 13 Q. Can't you verify that with Ms. 14 Mesner? 15 A. I don't know whether I can or 16 not. 17 Q. Why, why do you have some 18 uncertainty with respect to whether or not you 19 can verify that with her? 20 A. I am more certain about the 21 reports of the concrete paper documentation of 22 events. 23 Q. Wouldn't there be some 24 concrete documentation if a patient on Prozac in Page 332 1 that study committed suicide? 2 A. There certainly should be, 3 yes. 4 MR. MYERS: Wait a minute, let me 5 object to the form. Your question assumes the 6 patient was on Fluoxetine, I don't know that 7 that's been established by anybody. 8 MR. SMITH: I understand that. 9 MR. MYERS: Then I object to the 10 question. 11 MR. SMITH: It's my recollection of 12 what Ms. Mesner testified and can you do anything 13 to verify or dispute her testimony, she may have 14 been inaccurate. 15 MR. MYERS: I object to the form. I 16 don't think you got her testimony right entirely. 17 MS. ZETTLER: She did say that there 18 was a suicide that was committed on the study. 19 MR. MYERS: I think I might agree with 20 that. I just don't know about the other part of 21 the question. 22 MS. ZETTLER: She also said, Doctor, 23 that she had -- it was her recollection that she 24 had to fill out 1639s and 1639s were filled out Page 333 1 on virtually every patient in that study. 2 MR. MYERS: Hold on. Paul's asking 3 questions. Please do it one at a time or pass 4 him some notes, we're not going to have any 5 double teaming of the witness. 6 Q. (BY MR. SMITH) Doctor 7 Beasley, she also said that she had to fill out 8 1639s on virtually every one of the patients in 9 that study. Do you have any recollection of 10 that? 11 A. No, I don't. 12 Q. Would that be something that 13 you would recall if that were the case? 14 A. I'm saying I don't recall 15 that. 16 Q. Do you remember any particular 17 problems with adverse events that were reported 18 during that study? 19 A. I'm certain that there were 20 adverse events. 21 Q. What adverse events are you 22 certain occurred? 23 A. I don't recall any specific 24 adverse -- any specific adverse events. Page 334 1 Q. Whether it be rash, suicide, 2 attempted suicide, suicidal ideation? 3 A. That's correct. 4 Q. You know that your 5 investigator reported suicidal ideation as an 6 event that occurred in patients in that study? 7 A. Yes. That was a requirement 8 to get into the study. 9 Q. So is the answer to my 10 question yes? 11 A. Yes. 12 Q. Is it your testimony that 13 you're uncertain whether or not a suicide 14 occurred during that study or you're uncertain 15 with respect to who that individual who committed 16 suicide -- might have committed suicide was 17 taking Prozac? 18 A. Both. 19 Q. This was an important study 20 was it not, this pilot study done? 21 A. Yes. 22 Q. And the importance of it was 23 that it could lead to significant information 24 about a significant medical event? Page 335 1 A. I'm sorry, but I would 2 disagree with that statement rather strongly. 3 Q. Do you disagree that a suicide 4 is a significant medical event? 5 A. No. That's an extremely 6 tragic and significant medical event. 7 Q. So what is the basis of your 8 disagreement? 9 A. It is with regard to your 10 characterization of the purpose of the study. 11 Q. Wasn't the purpose of the 12 study to violate -- to validate a suicidal 13 ideation questionnaire? 14 A. To serve as a pilot for that 15 process, yes. 16 Q. And wasn't it the hope of you, 17 as the medical monitor, and Doctor Ivan Miller, 18 to come up with a sophisticated means for 19 assessing this significant problem, or sensitive 20 I think was the word you used yesterday? 21 A. Both. In this case it would 22 be both valid -- validity would be the primary 23 thing along with reliability for assessing the 24 phenomena that Doctor Teicher had described. Page 336 1 Q. And that is significant, is it 2 not? 3 A. That's correct. 4 Q. And this issue was bantered 5 back and forth between members of the Lilly 6 scientific community and the Food and Drug 7 Administration in several meetings, was it not? 8 MR. MYERS: Let me object to the form. 9 When you say this issue, the scale or the issue 10 of suicidality? 11 MR. SMITH: The scale and a validation 12 of that scale in some way. 13 A. Certainly the potential need 14 for a scale to assess what Doctor Teicher had 15 described was discussed. 16 Q. And is that the purpose of 17 this pilot study? 18 A. The pilot study was to -- a 19 beginning to develop an instrument hoped to be 20 able to, again, validly and reliably assess this 21 type of suicidal ideation. 22 Q. But as part of the pilot 23 study, patients weren't given Prozac by the 24 investigator as part of the protocol of the Page 337 1 study? 2 A. Correct. It was to look at 3 their suicidal ideation at baseline and then 4 changes and correlates or associations with other 5 scales, other behaviors to validate the scale. 6 Q. But there were patients that 7 incidently happened to be taking Prozac in the 8 study? 9 A. Again there were no 10 restrictions against patients receiving Prozac on 11 the study. Some may have done so. 12 Q. Well, some were in fact on 13 Prozac, weren't they? 14 A. Again, I am uncertain whether 15 or not that was the case. 16 Q. Wouldn't you know this as 17 medical monitor on the study whether or not there 18 were any patients in the study that were taking 19 Prozac? 20 A. Not necessarily. 21 Q. Did the study exclude 22 individuals receiving antidepressant therapy? 23 A. Absolutely not. 24 Q. And did the study contemplate Page 338 1 that there would be individuals in this study who 2 were on antidepressant therapy -- pharmacological 3 therapy? 4 A. Yes. 5 Q. And didn't the protocol 6 require that -- or the case report forms require 7 that there be an assessment of the patients with 8 respect to whether or not they were taking 9 medication such as antidepressants? 10 A. That had to be received, yes. 11 Q. And wouldn't the patient have 12 to identify what antidepressant they were taking? 13 A. The physician would identify 14 that. 15 Q. And wouldn't that be 16 transmitted to Lilly on the case report form? 17 A. Yes. 18 Q. And wouldn't Lilly record that 19 information? 20 A. Yes. 21 Q. Then why wouldn't you be aware 22 of it, Doctor, as the medical monitor on the 23 study? 24 MR. MYERS: Let me object to the form Page 339 1 of the question. Paul, he answered, he said he 2 doesn't know, he's told you that two or three 3 times. Now, tell him one more time, Doctor 4 Beasley. 5 A. I don't know. 6 MS. ZETTLER: That's not the question. 7 Q. My question is why would you 8 not be aware of it since you were the medical 9 monitor if the information was there at Lilly? 10 A. Because I would not look at 11 every case report form. 12 Q. Did you look at any case 13 report forms? 14 A. I can't recall looking at any 15 case report forms. 16 Q. You were the medical -- is it 17 your testimony here that you were the medical 18 monitor on this pilot study to determine the 19 validity of a scale that was going to be used to 20 assess the Teicher phenomenon and you didn't look 21 at any case report forms? 22 A. My testimony is that I cannot 23 recall looking at any case report forms. 24 Q. Did you talk with Doctor Page 340 1 Miller concerning any particular adverse events 2 that he reported or any of the investigators 3 reported on that study? 4 A. I can't remember such 5 conversations. 6 Q. Do you think that would be 7 something that you would recall had you done so? 8 A. I'm uncertain. 9 Q. Well, why are you uncertain 10 about that? 11 A. I don't recall. 12 Q. Would it be your practice as 13 the medical monitor to discuss adverse events as 14 they arose with the clinical investigator on the 15 study? 16 A. It would depend upon the 17 nature of the adverse event and the amount of 18 information that we had already obtained 19 regarding the event. 20 Q. The nature is suicide. 21 MR. MYERS: You're asking him to 22 assume there was such an event? 23 MR. SMITH: Yes. 24 Q. Would you talk to Doctor Page 341 1 Miller, whoever the investigator was in 2 connection with that? 3 A. Not necessarily. 4 Q. Under what circumstances would 5 you talk to the investigator were such that 6 reported -- were a report such as that given to 7 you? 8 A. At the request of the 9 investigator, if in reviewing information brought 10 to my attention for the purposes of completing 11 the 1639, I felt that there was inadequate 12 information and that it would be appropriate for 13 me as opposed to the DEU or the representative or 14 the clinical research associate to obtain that 15 information. 16 Q. As the clinical monitor, were 17 you required to sign off on any 1639s that 18 occurred during the study? 19 A. I may have signed off on 1639s 20 that occurred during the study. Other physicians 21 could have signed off as well. 22 Q. What other physicians? 23 A. Any back-up physician for me 24 who was available when I was not available. Page 342 1 Q. Who served as a back-up 2 physician for you on this study? 3 A. It -- again, it would depend 4 on who was available on the day that I was not. 5 Q. Do you recall anybody backing 6 you up on this study? 7 A. Not specifically, no. 8 Q. Do you recall any help that 9 any other physician gave you in this connection 10 at Eli Lilly and Company? 11 A. No. 12 Q. Did the protocol require that 13 you, as a clinical monitor, sign off on any 14 adverse event 1639s? 15 A. I can't recall that as part of 16 the protocol. 17 Q. Is that part of the Food and 18 Drug Administration regulations? 19 A. That I specifically sign the 20 form 1639? 21 Q. Yes. 22 A. I do not believe that is part 23 of the regulations. 24 Q. How long has this study been Page 343 1 ongoing, when did it begin and when did it end? 2 A. I believe it started sometime 3 in 1991. I'm uncertain about the length of last 4 patient enrollment. It was certainly in to 1992. 5 Q. For what period were patients 6 going to be observed during this study? 7 A. I don't recall the specific 8 number of weeks of observation. I believe it was 9 six. 10 Q. Now was Doctor Miller using 11 other psychiatrists or psychiatrist to administer 12 and to conduct this study? 13 A. I believe there were 14 co-investigators working him. 15 Q. Who were the co-investigators? 16 A. Again, he had an M.D. 17 associate who's name I don't recall. 18 Q. Who else? 19 A. I'm not sure who else would 20 have worked with him. 21 Q. As the medical monitor, do you 22 remember the names of any other co-investigators 23 on this study? 24 A. No. Page 344 1 Q. How many patients participated 2 in this study? 3 A. I don't recall the precise 4 number of patients who participated. It was a 5 relatively small number of patients, in the 6 orders of tens. 7 Q. Was this study conducted at 8 one site or multiple sites? 9 A. At one site. 10 Q. Where? 11 A. At Doctor Miller's hospital in 12 Providence, Rhode Island. 13 Q. You said Doctor Miller is not 14 an M.D.? 15 A. That's correct. 16 Q. He's a Ph.D psychologist? 17 A. That's correct. 18 Q. Did you respect his ability to 19 do this kind of study even though he did not have 20 an M.D. degree? 21 A. This, in fact, was his 22 particular area of expertise, scale development. 23 Q. And you didn't have any 24 problems with a Ph.D -- with a Ph.D's opinion in Page 345 1 this connection? 2 A. Opinion with regard to? 3 Q. The scale that you were trying 4 to validate. 5 A. That's correct. 6 Q. In other words, it's not only 7 medical doctors that might have some information 8 relevant to the issue of suicide and Prozac, is 9 it? 10 MR. MYERS: I object to the form to 11 the extent you're trying to equate that with your 12 earlier question. That's a different question 13 you're asking him. 14 MR. SMITH: It is a different 15 question. 16 MR. MYERS: Okay. I still object to 17 the form. 18 MR. SMITH: Because it's a different 19 question. 20 MR. MYERS: To the extent you're 21 trying to link it with your earlier question, 22 yes. 23 MS. ZETTLER: So he's objecting to 24 your objecting to your own perception, is that Page 346 1 what you're saying? 2 MR. SMITH: Leave Larry alone. 3 A. Would you please reread the 4 question? 5 Q. My question simply is, medical 6 doctors aren't the only individuals who can give 7 some information that would be of relevance to 8 the issue with respect to whether or not Prozac 9 causes suicide or violent aggressive behavior? 10 MR. MYERS: Well, wait a minute. I 11 object to the form of the question because that 12 may have to do with some evidentiary standards 13 either under the Federal Rules of Evidence or 14 under the various state rules, and that thus may 15 call for some kind of legal conclusion. But go 16 ahead and answer, Doctor. 17 A. Okay. I'm terribly sorry, but 18 could you read the specific question back again? 19 (QUESTION READ) 20 A. It's my opinion that there are 21 a number of professional training programs 22 besides that leading to Doctor of Medicine which 23 train people to serve and treat psychological and 24 behavioral disturbances. Those individuals are, Page 347 1 as I said, trained to observe and, therefore, 2 presumably to report data. Given that 3 suicidality is an aspect of things that these 4 people work with, they could presumably, 5 accurately report on suicidality. 6 Q. So a Ph.D psychologist with 7 the proper training would be able to make a 8 report such as this? 9 MR. MYERS: Same objection as to the 10 form. 11 A. Can accurately report on 12 psychological phenomena and behavior. 13 Q. And give impressions 14 concerning what their observations are. 15 MR. MYERS: Same objection as to the 16 form. 17 A. And certainly give 18 impressions. I mean the -- 19 Q. Additionally, Lilly has on 20 staff Ph.D statisticians that have provided 21 information that has been of critical importance 22 to you, haven't they? 23 A. Absolutely. 24 Q. So medical doctors, M.D. Page 348 1 behind their name doesn't mean that they can't 2 give some type of information that would be of 3 benefit in this issue, correct? 4 MR. MYERS: Same objection. 5 Q. I'm not trying to trick you, 6 Doctor Beasley. 7 A. I know and again, my -- and I 8 have said there are many people or many types of 9 training programs that train people to accurately 10 observe psychological phenomena and report those. 11 Okay. Now that's what I believe I can say, 12 that's my opinion. To the extent that they can 13 conjecture about causality is a, I think, a 14 somewhat different issue. 15 Q. Are you saying it takes an 16 individual with an M.D. degree to render an 17 opinion concerning whether or not Prozac is 18 caused by -- whether Prozac causes suicidality? 19 MR. MYERS: Same objection. 20 A. I'm not sure there's really 21 any difference in the quality of or the validity 22 of such statements, such beliefs. 23 Q. I don't understand what you're 24 saying. Page 349 1 A. I guess what I'm saying is 2 that in terms of the quality or the validity of 3 an M.D. versus a psychiatric social worker with 4 regard to conjecture about causality, I don't see 5 there being a substantial difference. 6 Q. All right. Now are you saying 7 that -- are you implying by your answer that any 8 opinion concerning causality in this issue would 9 be conjecture? 10 MR. MYERS: Same objection, and you 11 mischaracterized what he said, I think. Go 12 ahead. 13 A. It would be -- and from my 14 perspective, it would be an opinion. 15 Q. But people who are qualified 16 in our legal system can render opinions 17 concerning issues that are not known generally by 18 the population at large? 19 MR. MYERS: Is that the question? 20 Q. So are you saying that your 21 opinion on this issue is simply conjecture? 22 MR. MYERS: Object to the form. That 23 calls for a legal conclusion and that 24 mischaracterises his testimony. Go ahead and Page 350 1 answer Mister Smith's question. 2 A. Could -- you're asking me 3 about my opinion about -- 4 Q. Whether Prozac causes suicide 5 or violent agressive behavior. 6 A. That's my opinion. 7 Q. That it does? 8 A. No. 9 Q. That it is speculative, 10 conjecture? 11 MR. MYERS: Same objection as to the 12 form. 13 A. My opinion is that it does 14 not. 15 Q. All right. And that's not 16 conjecture on your part in your mind? 17 A. It's -- it is an opinion. 18 Q. But the opinion that you are 19 expressing in your mind is not conjecture, is it, 20 Doctor? 21 MR. MYERS: Finish the answer to your 22 question I think you started to finish, and then 23 answer his question. 24 A. It is opinion in that it is Page 351 1 something with which other people rightly or 2 wrongly might disagree. It is based upon my own 3 personal assessment of data and analyses that I 4 have looked at. 5 Q. And to be fair, that opinion 6 that you have come to -- that you have reached is 7 not supported by any dialogue or discussion that 8 you have had with any particular investigator 9 employed by Eli Lilly to report any particular 10 adverse event in connection with this issue? 11 A. That's correct. 12 Q. Now this scale that's being 13 validated in this pilot study is a suicidal 14 ideation scale, is it not? 15 A. That's correct. 16 Q. That doesn't have anything to 17 do with the separate study known as rechallenge 18 study, does it? 19 A. Actually it does. 20 Q. In what respect? 21 A. That would be an instrument 22 that would be used in a rechallenge study. 23 Q. But the suicidal ideation 24 scale could be used in any study, couldn't it? Page 352 1 A. It could be used to assess 2 patients or in no study or it could be used in 3 any study. 4 Q. And the FDA was suggesting 5 that you use some more sophisticated scale such 6 as the one that you have been attempting to 7 validate in some prospective study, correct? 8 MR. MYERS: I object to the form. At 9 what point in time? 10 MR. SMITH: At any point in time. 11 MR. MYERS: I object to to the form. 12 MR. SMITH: Especially April, May, 13 1991 when you were meeting with them. 14 A. It was certainly discussed. 15 Q. And they were suggesting it, 16 weren't they, that this more sensitive scale be 17 used in future studies? 18 A. That's my recollection, yes. 19 Q. And in addition to that, they 20 were suggesting that you do another type of study 21 known as a rechallenge study? 22 A. I don't recall that as an 23 absolute specific recommendation. 24 Q. Well, you did a rechallenge Page 353 1 protocol, didn't you? 2 A. We began developing one. 3 (PLAINTIFFS' EXHIBIT NO. 11 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. You have had an opportunity to 7 review Beasley Exhibit 11? 8 A. Yes. 9 Q. That is a document authored by 10 Doctor James G. Kotsanos, dated May 15th, 1991, 11 isn't it? 12 A. That's correct. 13 Q. And the subject of that 14 document is FDA meeting to discuss Fluoxetine 15 rechallenge protocol May 13th, 1991, isn't it? 16 A. That's correct. 17 Q. And that document reflects a 18 meeting at which you attended? 19 A. That's correct. 20 Q. And do you recall being there 21 at that meeting at the FDA? 22 A. Yes, I do. 23 Q. And do you recall that the 24 materials subject to this memo, Exhibit 13, were Page 354 1 discussed? 2 A. Yes. 3 Q. This exhibit says, At the FDA 4 meeting Lilly agreed to do the following 5 projects: One, proceed with the rechallenge 6 study. Correct? 7 A. That's what this memo says. 8 Q. Is that, in fact, what 9 occurred, Doctor Beasley, that is that at that 10 meeting Lilly agreed to -- with the FDA to 11 proceed with the rechallenge study? 12 A. I don't recall if in fact that 13 was agreed to or not. It was certainly discussed 14 at length. I cannot dispute Doctor Kotsanos' 15 documentation here. I do not recall whether or 16 not that was specifically agreed to. 17 Q. Did you take notes at that 18 meeting? 19 A. No, I did not. 20 Q. Doctor Kotsanos at least did a 21 memo concerning the subject of that meeting, 22 correct? 23 A. That's correct. 24 Q. His memo is dated May 15th, Page 355 1 two days after the May 13th, 1991 meeting, isn't 2 it? 3 A. That's correct. 4 Q. And wouldn't you agree with 5 me, Doctor Beasley, that probably Doctor Kotsanos 6 has an accurate reflection of what occurred 7 during that meeting? 8 MR. MYERS: I object to the form of 9 the question. That may call on him to speculate 10 as to what Doctor Kotsanos may know or recall. 11 Go ahead and answer, Doctor. 12 A. The only thing that I can say 13 is that these are in fact obviously Doctor 14 Kotsanos' recollections of the meeting. 15 Q. Have you ever had an 16 opportunity in all the years that you worked with 17 Doctor Kotsanos where his memory was inaccurate? 18 A. No. 19 Q. Have you ever seen an 20 inaccurate memo that he's prepared? 21 A. Not to my knowledge. 22 Q. Have you ever seen a false 23 memo that he's prepared? 24 A. Not to my knowledge. Page 356 1 Q. Have you ever seen him use a 2 term that wasn't used in its ordinary everyday 3 meaning? 4 A. Not to my knowledge. 5 Q. And Doctor Kotsanos in this 6 memo says, At the FDA meeting Lilly agreed to do 7 the following projects: One, proceed with the 8 rechallenge study. Doesn't he? 9 A. That's what he says, yes. 10 Q. You received this memo, didn't 11 you? 12 A. That's correct. 13 Q. Did you ever go to Doctor 14 Kotsanos and say hey, Jim, you're wrong, we 15 didn't agree to nothing there? 16 A. Not that I recall. 17 Q. We didn't and we're not going 18 to do the rechallenge study? 19 A. No, I don't recall that. 20 Q. Your memo is inaccurate? 21 A. No, I do not recall going to 22 Doctor Kotsanos and stating that his memo was 23 inaccurate. 24 Q. Don't you think you would have Page 357 1 some recollection of that had you done so? 2 A. Yes. 3 Q. You don't dispute then that 4 Lilly agreed to do a rechallenge study at the 5 meeting with the Food and Drug Administration on 6 May 13th, 1991, do you? 7 A. No. 8 Q. Now, item two of matters at 9 which Lilly agreed to do was to incorporate the 10 modified scale for suicidal ideation, correct? 11 A. Revised. 12 Q. Yes. Is my question correct 13 that Lilly agreed to incorporate the modified 14 scale for suicidal ideation revised in ongoing 15 and planned U.S. and UK clinical trials? 16 A. That is Doctor Kotsanos' 17 statement, yes. 18 Q. Do you disagree with that 19 statement, Doctor Beasley? 20 A. I don't disagree with that 21 statement. 22 Q. Is it inaccurate? 23 A. Not that I am aware of. 24 Q. Is it as accurate as anything Page 358 1 else he said here? 2 A. It would be as accurate as 3 anything else he says. 4 Q. Did you go to him and say when 5 you got this memo on May 15th or shortly 6 thereafter, Jim, you're wrong, we didn't agree to 7 incorporate the modified scale for suicidal 8 ideation revised in ongoing and planned U.S. and 9 UK clinical trials, did you? 10 A. No. 11 Q. Lilly had never done a 12 rechallenge study, have they? 13 A. No, we have not. 14 Q. Why not? 15 A. I am uncertain. We were -- 16 I'm uncertain, which means more accurately I 17 don't know. 18 Q. You drew up the rechallenge 19 protocol, didn't you, Doctor Beasley? 20 A. I drew up a draft of the 21 rechallenge protocol, yes. 22 Q. You told me earlier that you 23 were the medical doctor primarily responsible for 24 doing this, weren't you? Page 359 1 A. That's correct. 2 Q. Did you ever ask anybody at 3 Eli Lilly and Company why haven't we done the 4 rechallenge protocol that I put in a substantial 5 amount of time and labor on? 6 A. Not explicitly, no. 7 Q. Did you by implication ask 8 that? 9 A. I have certainly discussed the 10 rechallenge protocol with various management 11 individuals through the process following the 12 1991 meeting with the FDA and then progressively 13 through that time. I can't recall the last 14 conversation that I had regarding that. 15 Q. In any of these discussions or 16 any of these conversations, did you ever put the 17 question to them why haven't we done what we 18 agreed with the FDA that we would do, that is 19 perform a rechallenge on patients to make some 20 determination concerning whether or not this drug 21 might be linked to this serious adverse event? 22 A. I can't recall doing so 23 explicitly, no. 24 Q. Are you saying that you don't Page 360 1 recall or that you didn't do it? 2 A. I'm saying I don't recall. 3 Q. Is this something that you 4 would recall had you posed this question? 5 A. I don't know. 6 Q. Do you think this would be 7 something you would forget? 8 A. The exact wording of my 9 conversations, yes, I believe I would. 10 Q. Do you think you may have 11 forgotten a generality as to -- in general terms 12 putting to some body in medical management the 13 question as to why the rechallenge protocol 14 wasn't done? 15 A. I have indicated that I have 16 discussed it, but I can't recall the specifics of 17 those discussions. 18 Q. All right. Did you get any 19 answer from anybody in medical management as to 20 why this hadn't been done? 21 A. I don't recall a specific 22 answer. 23 Q. Do you recall a general 24 answer? Page 361 1 A. It would be speculation on my 2 part. 3 Q. Speculation on your part. Is 4 that because you don't know as you sit here why a 5 rechallenge protocol wasn't done? 6 MR. MYERS: I object to the form. 7 He's answered that question, Paul, he said he 8 didn't know, he told you that twice. 9 Q. I understand that, but my 10 question now is didn't you ever ask anybody why 11 it wasn't done? 12 A. And what I have said, I cannot 13 recall putting that explicit question to anyone. 14 Q. Do you recall putting that 15 general question to anyone? 16 A. As I said, I can recall having 17 conversations about the rechallenge protocol and 18 the progress that we were making with the 19 development of the MSSIR. 20 Q. I'm not worried about the 21 MSSIR now, I'm worried about the rechallenge 22 protocol which is a separate protocol, is it not? 23 A. That's correct. 24 Q. Is it dead, is there not going Page 362 1 to be a rechallenge protocol done? 2 MR. MYERS: Hold on. Paul, lower your 3 tone of voice, he can hear you and I can hear you 4 perfectly well. You need not raise your voice, 5 please. 6 MS. ZETTLER: Let the record reflect 7 that Mister Myers is mischaracterizing Mister 8 Smith's tone of voice. 9 MR. MYERS: He's raising his voice 10 Nancy. Go ahead and answer the question, Doctor. 11 A. Quite frankly, I don't know. 12 We are as I have said, still completing the 13 analysis of the scale. That would need to be 14 done before a rechallenge protocol can be done 15 with that scale incorporated into it. 16 Q. Well, that poses another 17 question to me then, Doctor. In Exhibit 11, 18 Doctor Kotsanos says that Lilly agreed to have 19 the rechallenge protocol ready to go by September 20 1st, 1991 and to provide data after the first 21 quarter which would provide information on six 22 months of experience. Look at page one. Do you 23 see that? 24 A. Yes, I do. Page 363 1 Q. So I don't get the impression 2 from reading that that the rechallenge protocol 3 was going to have to be held up to wait for some 4 MSSI-R being validated by some pilot study and 5 that pilot study be completed before you could do 6 the rechallenge study? 7 MR. MYERS: Let me object to the form 8 as to what your impression is or is not. 9 Q. What is your impression, 10 Doctor Beasley? 11 A. My impression was it was 12 clearly felt that that was central to the whole 13 rechallenge protocol. 14 Q. Then why? 15 MR. MYERS: Let him finish, Paul. Go 16 ahead, Doctor. 17 A. Okay. That decision evolved 18 through the summer and there were substantial 19 issues raised about conducting the study to 20 validate the MSSI-R. 21 Q. Then why would you have agreed 22 with Doctor Leber and high ranking officials at 23 the Food and Drug Administration, and Doctor 24 Leigh Thompson was there at that meeting, wasn't Page 364 1 he? 2 A. As I recall Doctor Thompson 3 was not the senior ranking individual at that 4 meeting. 5 Q. Well, he was there, wasn't he? 6 A. No. That's -- as I recall, I 7 do not believe that Doctor Thompson was attending 8 this particular meeting. 9 Q. Who was the senior ranking man 10 there? 11 A. My recollection is that it 12 would have been Doctor Zerbe. 13 Q. Why would you -- whoever it 14 was, why would Lilly have agreed to have a 15 rechallenge protocol ready to go by September 16 1st, 1991? Let's see, that's two and a half 17 years ago, isn't it? 18 A. That's correct. 19 Q. That it was going to be ready 20 to go, quote, right? 21 A. That's correct. 22 Q. And if you were going to have 23 data after the first quarter which would provide 24 information on six months of experience, right? Page 365 1 A. I'm not sure that the 2 reference to six months of experience relates to 3 the rechallenge protocol, it may very well. 4 Q. Would you agree with me that 5 it's under -- it's a bullet point under point 6 one, proceed with the rechallenge study? 7 A. That's correct. 8 Q. And would you agree with me 9 that there is nothing in that paragraph 10 concerning a validation study or concerning any 11 suicidal ideation scale, modified or revised? 12 A. I would absolutely agree with 13 that. 14 Q. So as just an individual that 15 wasn't there at the meeting, Doctor Beasley, it 16 looks to me like Lilly has agreed to start a 17 rechallenge study and to get some data by 18 September 1st, doesn't it? 19 MR. MYERS: I object to the form. 20 It's not at all relevant as to what you think or 21 don't think and it mischaracterizes what he and 22 others have said. Do you want to know if he 23 agrees with your assessment, is that what you 24 want to know? Page 366 1 MR. SMITH: Yes. 2 A. I would agree that on May 3 15th, Doctor Kotsanos clearly believed that we 4 had agreed to conduct such a study and to have -- 5 I'm not sure what he means by rechallenge 6 protocol ready to go, whether he means initiated, 7 submitted, I'm uncertain, by September 1, 1991. 8 Q. You were going to be the 9 medical monitor on this trial, weren't you? 10 MR. MYERS: That's been asked and 11 answered four times. Don't answer it again, 12 Doctor Beasley. He's not going to answer that 13 question anymore, go ahead and ask him another 14 question. 15 Q. Is this rechallenge protocol 16 that they're discussing in this May 15th, 1991 17 memo a rechallenge study that you were going to 18 be the medical monitor on or are we talking about 19 some other rechallenge protocol study? 20 A. I had begun working on -- I 21 had begun working. 22 MR. MYERS: Great question, go ahead. 23 A. I had begun working on the 24 development of such a protocol. Whether or not Page 367 1 if such a protocol came into effect I would be 2 the medical monitor for it or not, would be hard 3 to say because to this point in time, it has not 4 come into being. I began working on such a 5 protocol. I could have been reassigned at any 6 point and someone else could have been assigned 7 to it. 8 Q. But when you were working on 9 the protocol, at all times you were under the 10 impression that you were going to be the medical 11 monitor? 12 A. I was working on it, that's 13 correct. 14 Q. You were working on the 15 protocol with the impression that you were going 16 to be the medical monitor? 17 A. That's correct. 18 Q. Did you ever go to Doctor 19 Kotsanos and say you're seriously mistaken about 20 this statement that we would have a protocol 21 ready to go by September 1st, 1991 and would 22 provide data by after the first quarter which 23 would provide information on six months 24 experience? Page 368 1 A. I believe I've indicated 2 previously that I never went to Doctor Kotsanos 3 and told him that his memo was in error. 4 Q. Did you believe at the time 5 that this was going to be accomplished, Doctor 6 Beasley? 7 MR. MYERS: I object to form. When 8 you say this, there are a lot of things in the 9 memo. What are you making reference to? 10 MR. SMITH: This September 1st, 1991 11 protocol being -- rechallenge protocol being 12 ready to go and there being data accumulated. 13 A. Given the work that I was 14 doing with the MSSI-R, and the development of the 15 protocol, it would have seemed most unlikely to 16 me, this is -- that one could initiate a protocol 17 by that point in time. 18 Q. Did you say, stop, we've left 19 the wrong impression with the Food and Drug 20 Administration, we told them that we're going to 21 have something done in a particular period of 22 time and I'm working on this validation study and 23 there's no way we can have that done by September 24 1st, 1991? Page 369 1 MR. MYERS: Let me object to the form. 2 It would be speculative for him to assume what 3 the FDA's impression was. Go ahead and answer. 4 A. I did not -- I'm sorry, could 5 you read the question again? 6 (QUESTION READ.) 7 A. I did not go specifically to 8 Doctor Kotsanos and tell him that. 9 Q. Did you go to anybody? 10 A. The protocol for the MSSI-R 11 validation was certainly discussed and the -- its 12 development and its incorporation into the 13 rechallenge study, if we did the rechallenge 14 study, was certainly something that had been 15 generally discussed in multiple meetings. 16 Q. Doctor Beasley, is it your 17 testimony here that the rechallenge study was not 18 done because the validation study had not been 19 completed? 20 A. No. 21 Q. I'm going to make sure I am 22 clear on this. Did you ever hear any reason 23 given by anybody in medical management as to why 24 the rechallenge study hasn't been done? Page 370 1 A. I do not recall hearing a 2 specific reason from anyone why -- 3 Q. I'm sorry, I didn't mean to 4 cut you off. 5 A. -- why the rechallenge study 6 has not been done. 7 Q. Do you recall a general reason 8 given by anybody as to why the rechallenge 9 protocol has not been done? 10 A. No. 11 Q. Do you have an opinion as to 12 why it's not been done? 13 A. Yes, I do. 14 Q. What is that opinion? 15 A. There were a lot of 16 interactions and evolution around the issue 17 following the May meeting with the FDA. An 18 unexpected meeting was the calling of the 19 Advisory Committee. There were a number of 20 conversations I would believe that went on 21 between medical management and the FDA in terms 22 of preparing and developing documentation for 23 that. I believe that the outcome of that 24 Advisory Committee Meeting and the last, as I Page 371 1 understand it, the last -- that being the last 2 meeting with the FDA by Lilly formally regarding 3 this issue, may have impacted on decisions with 4 regard to timing and when -- or when this 5 rechallenge protocol would not be done. 6 Q. I think I asked you this 7 question, but I'm not sure what the answer was. 8 Do you know of any existing plan to do the 9 rechallenge study? 10 A. No, not at this time. 11 Q. Have you seen any memo that 12 has indicated that the rechallenge study will not 13 be done? 14 A. Will? 15 Q. Not be done. 16 A. Not be done. I don't think 17 I've seen any. 18 Q. That's just the general 19 understanding that it will not be done? 20 A. Yes. 21 MR. SMITH: Let's go to lunch a little 22 early. 23 (DISCUSSION OFF THE RECORD.) 24 MR. SMITH: Did you find anything Page 372 1 about the request I made yesterday? 2 MR. MYERS: With respect to the 3 request you made yesterday, what I can tell you 4 is that we -- I'm going to have brought over 5 hopefully today over the lunch break the 1639s 6 from the study. We're not in a position to give 7 you the report because there is not a report. 8 But the 1639s on suicide attempts and any other 9 suicide related 1639s from the study. 10 MR. SMITH: All right. And you think 11 they will be here at lunchtime? 12 MR. MYERS: I hope so. 13 MR. SMITH: Groovy. 14 MS. ZETTLER: Doctor Beasley, you just 15 looked a little puzzled when Larry said that 16 there was not a report, why is that? 17 THE WITNESS: There is not a final 18 report. Clearly I have worked on drafts, I was 19 just wondering about the distinction between 20 drafts and a report. 21 MS. ZETTLER: So there are drafts that 22 exist? 23 THE WITNESS: There are drafts that 24 exist. Page 373 1 MS. ZETTLER: And it really is in the 2 final stages before it's submitted to the FDA, is 3 it not? 4 THE WITNESS: I'm not certain about -- 5 I think it's close, but it's not there yet. 6 MS. ZETTLER: It's in regulatory? 7 THE WITNESS: Actually I think there 8 is another physician that needs to do some work 9 since it's intended to submitted with some other 10 documentation. 11 MS. ZETTLER: What other 12 documentation? 13 THE WITNESS: A potential label 14 change, the draft package labeling. 15 Q. (BY MR. SMITH) Label change 16 on Prozac? 17 A. Yes. 18 Q. What label changes are 19 contemplated on Prozac? 20 A. The reflection that we now 21 have extensive long-term data that's positive in 22 terms of efficacy. 23 Q. But does that label change 24 have anything to do with respect to safety? Page 374 1 A. It's primarily efficacy and an 2 indication that we have experience. 3 Q. Experienced what? 4 A. Long-term experience with the 5 administration of the drug. 6 Q. Will that long-term experience 7 portion describe the safety? 8 A. Only that we have -- it may, I 9 am not writing that. 10 Q. Okay. Do you know what 11 details of safety that label change might entail? 12 A. Not specifically, no. 13 Q. Who is the other physician 14 that is working on that? 15 A. Doctor Pande. 16 Q. Is he the individual that 17 still may have to look at the report? 18 A. That's correct. 19 Q. All right. 20 (A SHORT LUNCH RECESS WAS TAKEN.) 21 MR. MYERS: In response and in 22 follow-up to the request Mister Smith made 23 yesterday, I initiated an inquiry to be furnished 24 with the 1639s from the study that Doctor Beasley Page 375 1 discussed for some period of time yesterday with 2 respect to suicidality. And that is what I have 3 been given and what I in turn have turned over to 4 plaintiffs' counsel. I have every reason to 5 believe that those are the 1639s from that study 6 dealing with the subject of suicidality. In view 7 of the expediency with which I obtained those 8 documents, I can't warrant that, but I have every 9 reason to believe that those are them and that's 10 what I have given you all this afternoon. 11 MR. SMITH: All right. And we 12 appreciate your efforts to do this. However, we 13 had made a request for information over and above 14 the 1639s and I don't want to -- don't want it 15 understood that by accepting the 1639s that we 16 are in any way withdrawing our request for the 17 additional information. 18 MR. MYERS: I understand that. 19 MR. SMITH: But we appreciate you 20 furnishing this to us. 21 MR. MYERS: You are very welcome. 22 * * * * * * * * * * 23 CROSS EXAMINATION 24 BY MS. ZETTLER: Page 376 1 Q. Doctor Beasley, I introduced 2 myself yesterday and my name is Nancy Zettler and 3 I am plaintiffs' attorney and co-counsel with 4 Paul on the Fentress case in Louisville, Kentucky 5 that a bunch of cases that stem from the actions 6 of Joseph Wesbecker in September of 1989. Are 7 you familiar with that case? 8 A. Yes. 9 Q. Okay. I am also plaintiff's 10 counsel with -- for two cases in Chicago -- 11 outside of Chicago in Illinois. What do you know 12 about the Wesbecker case? 13 A. I know that a Mister Joseph 14 Wesbecker entered either his place of employment, 15 I believe, or his his former place of employment, 16 had on his possession a number of guns and shot a 17 number of individuals. 18 Q. And then committed suicide? 19 A. And then committed suicide. 20 Q. Have you talked to anybody in 21 Kentucky, outside of a lawyer, okay, about the 22 Wesbecker incident at any time? 23 A. No. 24 Q. Have you talked to the coroner Page 377 1 in Louisville? 2 A. I do not believe that I talked 3 to the coroner. I believe that I was present 4 during a phone call to the coroner. 5 Q. Okay. When you say a phone 6 call, you were present during a phone call to the 7 coroner, are you talking about a phone call, a 8 conference call of sorts, like more than one 9 person in the room on your end with the coroner 10 or the coroner and somebody else on the other end 11 of the line? 12 A. Yes. But I don't believe it 13 was a speaker phone if I recall correctly. 14 Q. Who was on the direct line 15 with the coroner from Louisville? 16 A. And again, I'm believing that 17 I recall this correctly, that either Doctor Zerbe 18 or Doctor Masica would have been on the phone 19 with the coroner. 20 Q. Did Lilly initiate that phone 21 call or did the coroner? 22 A. This is -- may have been a 23 follow-up to a call that was initially initiated 24 by the coroner. Page 378 1 Q. Okay. Do you recall his name 2 as being Doctor Greathouse? 3 A. Yes, I do. 4 Q. Have you ever spoken to Doctor 5 Greathouse personally? 6 A. I do not believe I have. 7 Q. Have you ever corresponded 8 with Doctor Greathouse? 9 A. I don't think I have had any 10 letters that I have personally signed to Doctor 11 Greathouse, no. 12 Q. How about Doctor Coleman, Lee 13 Coleman, have you ever heard that name before? 14 A. I believe that that was his, 15 Mister Wesbecker's psychiatrist. 16 Q. Have you ever talked to Doctor 17 Coleman? 18 A. No, I don't believe I have. 19 Q. To your knowledge, has anybody 20 from Lilly talked to Doctor Coleman outside of 21 their counsel? 22 A. I'm uncertain if anyone has 23 spoken with him. 24 Q. Why are you uncertain? Page 379 1 A. I don't know if any of the 2 other research physicians or any other physician 3 at Lilly or in the DEU might have spoken with 4 him. 5 Q. Have you ever corresponded 6 with Doctor Coleman? 7 A. I don't believe I have. 8 Q. To your knowledge, has anybody 9 from Lilly corresponded with Doctor Coleman? 10 A. I don't know. 11 Q. Do you know if Doctor Coleman 12 was sent a 1639 on the Wesbecker incident? 13 A. No, I don't. 14 Q. Would that have been Lilly's 15 policy back then, after hearing about the 16 Wesbecker incident to send a 1639 to Doctor 17 Coleman? 18 A. No, that would not be my 19 understanding of Lilly's policy. 20 Q. Why not? 21 A. I do not know why it was not 22 our policy to send 1639 reports to the physicians 23 of patients on whom 1639s were filed. 24 Q. Doctor, even though I don't Page 380 1 have an example with me, we've seen a number of 2 instances where there have been letters from 3 Lilly to what appears to be physician reporters 4 of incidents enclosing draft 1639s for their 5 review. Are you saying that's not your 6 understanding of what Lilly's policy was? 7 A. No, I'm not. I believe that 8 you've just stated that there have been occasions 9 where we have sent reports, 1639s to reporting 10 physicians. That would be the case when 11 additional information was desired. 12 Q. Was a 1639 filed on the 13 Wesbecker incident, to your knowledge? 14 A. I'm virtually certain it was. 15 Q. Who would have been considered 16 the reporter of that event, Doctor Greathouse? 17 A. I believe that Doctor 18 Greathouse was the first reporter of that event. 19 Q. Would the 1639 have been sent 20 to Doctor Greathouse? 21 A. It -- I don't know if the 1639 22 was or was not sent to him. It might have been 23 sent to him if there was a feeling that there was 24 additional information that needed to be obtained Page 381 1 that he would not have communicated through other 2 means. 3 Q. To your knowledge, had anybody 4 from Lilly contacted Doctor Coleman to inquire 5 about the Wesbecker incident in preparation for 6 filing a 1639? 7 A. I'm not aware of any such 8 contact. 9 Q. And it's your understanding 10 that it would not have been Lilly's policy to 11 send a 1639 report to Doctor Coleman in that 12 situation, back in 1989, because he was not the 13 initial reporter of the event? 14 A. That would be my 15 understanding. 16 Q. Are you aware that Mister 17 Wesbecker saw Doctor Coleman three days before he 18 went to Standard Gravure and shot a bunch of 19 people and himself? 20 A. Now that you ask the question 21 in that -- in the way that you have, giving me 22 the three days, I believe that I understand that 23 to be the case. You have refreshed my memory. 24 If you had asked me how many days was the last Page 382 1 time -- how many days did Mister Wesbecker see 2 Doctor Coleman before the event, I don't think I 3 could have given you the specific number. 4 Q. But now that I have brought it 5 up, you recall that three days before the event 6 Mister Wesbecker did visit Doctor Coleman? 7 A. I believe that is the correct 8 number. 9 Q. Are you aware that in Doctor 10 Coleman's last note for that visit with Mister 11 Wesbecker, he saw that Mister Wesbecker was 12 suffering from increased agitation and anger? 13 A. I believe that that's the 14 case. 15 Q. Are you aware that Doctor 16 Coleman put in his note that he questioned 17 whether or not this increase in agitation and 18 anger was attributable to Prozac? 19 A. I believe that's the case. 20 Q. Then why wouldn't somebody 21 from Lilly call Doctor Coleman -- or at least to 22 your knowledge, call Doctor Coleman to inquire 23 about his thoughts on the use of Prozac and 24 Mister Wesbecker's deteriorated condition? Page 383 1 A. I do not know why such a call 2 was not made. From the conversation that we have 3 just had, it appears to me that we at some point 4 became aware that the physician did in fact 5 indicate that in his opinion this was a 6 possibility. 7 Q. But you don't know why the 8 call wasn't made to Doctor Coleman to discuss his 9 note with him? 10 A. That's correct. 11 Q. Do you know if the fact that 12 Doctor Coleman's final note regarding Joseph 13 Wesbecker questions whether or not Prozac was 14 increasing his anger and agitation and causing a 15 deterioration in his condition was ever submitted 16 to the FDA in the form of a 1639? 17 MR. MYERS: Let me object to the form 18 because I don't think you precisely stated what 19 the note says. But go ahead and answer if you 20 know. 21 A. I cannot recall the contents 22 of the 1639s nor their updates. 23 Q. How many times was the 1639 on 24 Joseph Wesbecker updated to your knowledge? Page 384 1 A. I don't know. 2 Q. Are you aware that there was 3 at least one update that Lilly filed with regards 4 to the 1639 on Wesbecker that included 5 information about how many guns he had had in his 6 possession at the time? 7 A. I'm not aware of that. 8 Q. Would you consider such 9 information relevant to the event that occurred 10 on September 14th, 1989 involving Joseph 11 Wesbecker? 12 A. The number of guns? 13 Q. Yes. 14 A. It certainly is a piece of 15 information that presumably became available. 16 I'm having a hard time sitting here making a 17 personal decision about how relevant it is over 18 and above the actions that he took, the specific 19 number of guns. If I had filled out the 1639 20 initially -- again, this is retrospective -- if I 21 filled out the 1639 initially and had that 22 information available, I might or might not have 23 included it. 24 Q. Who makes a decision on when a Page 385 1 1639 on an event should be updated, in what 2 circumstances? 3 A. It can be a variety of 4 circumstances. Information may come in directly 5 to the drug epidemiology unit or may come in to a 6 physician, again, this is within Lilly, and the 7 person receiving such information would need to 8 make the initial decision as to whether or not it 9 would be possible that the 1639 should be 10 updated. That would generally be something if an 11 update occurred, would be signed off on by a 12 physician. 13 Q. What do you mean when you say 14 whether it was possible for the 1639 to be 15 updated? 16 A. Obviously, the person first 17 receiving the information would have to in some 18 sense share that with the individual responsible 19 for putting that on a 1639 update form, or put 20 that on a 1639 update form themselves, and then 21 that would ultimately need to be signed off on by 22 a physician. 23 Q. Do you know of any prohibition 24 by Lilly where information that comes in on a Page 386 1 follow-up or additional information on an event 2 cannot be placed on a follow-up 1639? 3 A. No. 4 Q. Okay. Do you know any such 5 prohibition by the FDA? 6 A. No. 7 Q. How many studies related to 8 the use of Fluoxetine and suicidality in any form 9 have been conducted by Lilly before or after 10 1990? 11 A. I need to understand your 12 specifics of the question. Could you -- 13 Q. Sure. What I'm trying to find 14 out is how many studies, and I'm not talking 15 about a reanalysis of prior studies like you did 16 with your meta-analysis, I'm talking actually 17 clinical trials that have been conducted to 18 investigate Fluoxetine and suicidality, either a 19 causal relationship or a prophylactic 20 relationship, any type of relationship between 21 Fluoxetine and the use of suicidality. 22 A. At any time? 23 Q. At any time. 24 A. There was one study conducted Page 387 1 with the principle investigator being Doctor 2 Stewart Montgomery. This study was conducted in 3 Europe, I believe in the United Kingdom, by 4 Doctor Montgomery. 5 Q. Any others? 6 A. I can't recall any additional 7 studies where suicidal acts or suicidal thoughts 8 were the specific primary goal of the study. 9 Q. When you say suicidal acts or 10 suicidal thoughts were the specific primary goal, 11 what do you mean? 12 A. To study suicidality, either 13 ideation or acts, prevention or causality. 14 Q. Okay. How about a personality 15 disorder patient suicide attempt or study? 16 A. That was the nature of Doctor 17 Montgomery's study. 18 Q. How about abstract NR358? 19 A. I'm not familiar with that. 20 (PLAINTIFFS' EXHIBIT NO. 12 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 A. I've read the memo. 24 Q. Before I ask you a question Page 388 1 about that, I have one follow-up question about 2 the 1639 on Wesbecker. To your knowledge, who 3 would have filed that 1639 or who would have been 4 in charge of signing off on that 1639? 5 A. It could have been a variety 6 of people that would have signed off on the 1639. 7 Q. Can you give me some names? 8 A. It could have been myself. At 9 the time, I believe, Doctor Heiligenstein was 10 possible. If Doctor Street were here at the 11 time, she could have signed off. Doctor Masica 12 could have signed off. Potentially Doctor Zerbe, 13 but I don't think he would routine practice sign 14 off on 1639s. 15 Q. To your knowledge, was the 16 1639 regarding the Wesbecker incident filed 17 before or after the policy change at Lilly 18 regarding assigning causal relationship to every 19 adverse event? 20 A. I believe it would have been 21 filed before. 22 Q. Before. So it should have 23 been causally related, should have been marked as 24 possibly causally related? Page 389 1 A. That would ultimately be the 2 decision of the individual who did the assigning. 3 Q. With regards to that -- I'm 4 sorry, let's digress a little bit from that, you 5 don't have to look at that one right now. 6 A. Okay. 7 Q. With regards to the assignment 8 of possibly causally related, is that something 9 that's actually put on the 1639? 10 A. That is -- I believe that on 11 the FDA form 1639 there is a place where that is 12 noted. 13 Q. Okay. So we've got examples 14 that Larry was talking about earlier. Without 15 marking any of these as an exhibit, at this time, 16 could you show me and the first 1639 where you 17 believe that would be indicated? 18 A. This was an expected event so 19 causality would not have been assigned. 20 Q. Okay. So because you look at 21 it as whether or not it is expected or 22 unexpected? 23 A. That's correct. 24 Q. And if it's unexpected, Page 390 1 causality would have been automatically assigned 2 back before 1990? 3 A. On the form that we use, that 4 the clinicians use to go from this to a form 5 1639, there is an exception to that and that 6 happens to be if there is a -- if the report 7 involves a legal case, and then a star with no 8 assignment gets placed. The -- again, what I 9 have given you is my policy. Whether or not that 10 was my interpretation of what I believe was the 11 strong Lilly statement across medical, whether or 12 not that was acted upon by the sign off on the 13 1639, I don't know. 14 Q. So when you discussed with 15 Paul earlier your belief that it was Lilly's 16 policy prior to early 1990 that all unexpected 17 serious events were to be marked possibly 18 causally related, that is your impression of your 19 understanding of what the policy was? 20 MR. MYERS: Let me object to the form. 21 I don't think his testimony was that all of them 22 were marked reasonably possibly causally related. 23 I don't think you accurately stated his 24 testimony. Page 391 1 Q. Well, my understanding from 2 what you said yesterday, Doctor, is that all 3 adverse events, prior to 1990, regardless, in the 4 conservative policy of Lilly, at least as you 5 understood it, were marked reasonably causally 6 related. 7 MR. MYERS: I object to the form, 8 that's not what he said. 9 MS. ZETTLER: That's why I'm asking. 10 A. That's not quite correct. 11 Q. Tell me what -- 12 A. What I said was unless there 13 were substantial or overwhelming reasons to 14 believe that that was not the case, that that was 15 the approach that I took, that I believe that in 16 general physicians took around the issue of 17 Prozac. 18 Q. Did you ever have a meeting 19 with the physicians or discuss that policy with 20 other physicians in the group? 21 A. Yes, we did. And again, that 22 was when we had this meeting that I was 23 discussing yesterday to make some decision about 24 what to do about the reports of suicidality that Page 392 1 were coming to us with extremely sparse clinical 2 information, frequently secondhand or thirdhand 3 reports from lay literature. 4 Q. Were you involved with the 5 decision to map suicide attempts using drugs as 6 overdoses as opposed to suicide attempts using 7 drugs as an event term? 8 MR. MYERS: Let me just object to the 9 form to the extent you're suggesting it could be 10 done both ways. I don't know that anybody's 11 testified it can or can't. Go ahead. 12 A. There is a dictionary, there 13 have been a series of dictionaries that have been 14 provided to the clinicians by regulatory to 15 assign mappings of events. 16 Q. Right. That's not my 17 question. It's our understanding, Doctor, from 18 previous testimony, that sometime in late 1989 19 the physicians got together and made the decision 20 to begin mapping suicide attempts where a drug 21 was used to the event term overdose as opposed to 22 some other term. Do you recall that happening? 23 MR. MYERS: Let me object to the form 24 to the extent you tried to synthesize a group or Page 393 1 bunch of testimony. I don't know if you 2 accurately portrayed it or not. But tell her if 3 you know. 4 A. No. 5 (PLAINTIFFS' EXHIBIT NO. 13 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 A. I have read the memo. 9 Q. Okay. Doctor, Exhibit 13 10 appears to be an E-mail from Rick Huddleston to 11 Mike Noone, Max Talbott and a few other people as 12 CCs, correct? 13 A. That's correct. 14 Q. And it's dated November 28th, 15 1990, is it not? 16 A. That's correct. 17 Q. The subject matter of the 18 E-mail is the decision in late 1988 or early 1989 19 by Prozac research physicians to begin mapping 20 intentional overdoses to overdose, correct? 21 A. That's what I believe I am 22 reading here. 23 Q. Were you aware of that policy 24 change? Page 394 1 A. I do not recall this policy. 2 Q. Okay. Are you aware that 3 Lilly mapped suicidal ideation to the event term 4 depression? 5 A. Yes, I am. 6 Q. When did you become aware of 7 that? 8 A. I can't recall the first time 9 that I had occasion to look at an adverse event 10 description of suicidal ideation at that time 11 because it would have gone to the dictionary. 12 Q. Do you personally have a 13 problem using the event term depression to 14 describe suicidal ideation? 15 A. I do not believe that it is as 16 specific as the actual term suicidal ideation 17 which does not exist in the dictionary that we 18 use. 19 Q. Are you using the Co-start or 20 ELECT dictionary at this time? 21 A. At this time we're using the 22 Co-start dictionary. 23 Q. When did you start using the 24 Co-start dictionary? Page 395 1 A. We, I think, switched from the 2 ELECT dictionary over a year ago, but that's an 3 approximation. 4 Q. The ELECT dictionary was a 5 dictionary that was put together by Lilly based 6 on the Co-start, correct? 7 A. That's my understanding. 8 Q. It was essentially the same 9 with a few event terms that had been added or 10 deleted depending on how you compared the two? 11 A. That's my understanding. 12 Q. Would there have been any 13 prohibition for Lilly to have placed or mapped 14 suicidal ideation to suicidal ideation in its own 15 dictionary? 16 MR. MYERS: Assuming they have it in 17 there that way. 18 MS. ZETTLER: I think he said that it 19 wasn't, but -- 20 MR. MYERS: Right. 21 A. It was not in the dictionary 22 as an ELECT or Co-start term to my understanding. 23 Q. What I'm asking you is do you 24 know of any prohibition to Lilly having placed Page 396 1 the event term suicidal ideation in its 2 dictionary and mapping the synonym suicidal 3 ideation to that event term as opposed to mapping 4 it to depression? 5 A. I don't know of any 6 prohibition. 7 Q. Has anybody given you an 8 explanation why suicidal ideation maps to 9 depression either in the ELECT dictionary or the 10 Co-start? 11 A. No. 12 Q. Have you asked? 13 A. No. 14 Q. Have you raised the question 15 as to whether or not there is some more specific 16 event term that suicidal ideation could map to 17 besides depression, at any time? 18 A. No. 19 Q. Are you aware of anybody 20 employed by Lilly either now or before that has 21 raised that issue? 22 A. I'm not aware of anyone that 23 has raised the issue. 24 Q. At the beginning of this Page 397 1 E-mail, it says, The following is an extension of 2 Leigh's response/explanation to Claude Bouchy 3 regarding the changing of event terms and/or text 4 on ADE's from Europe. Do you see that? 5 A. Yes. 6 Q. Were you aware that -- did you 7 know Claude Bouchy? 8 A. No. 9 Q. Do you know Hans Weber? 10 A. Yes, I do. 11 Q. How do you know Doctor Weber? 12 A. Doctor Weber was a physician 13 working in Indianapolis at McCarty Street where I 14 worked several years ago. 15 Q. To your knowledge, is Doctor 16 Weber still employed by Lilly? 17 A. Yes, he is. 18 Q. Where is he? 19 A. He is medical director in 20 Germany. 21 Q. To your knowledge, does Doctor 22 Weber have any plans to return to the United 23 States in the near future? 24 A. I am unaware of Doctor Weber's Page 398 1 plans. 2 Q. Were you aware that Doctor 3 Weber and Doctor Bouchy raised the issue with 4 Doctor Thompson of changing event terms on 5 reports of suicide attempts and suicidality to 6 overdose and depression respectively? 7 A. No, I was not. 8 Q. Okay. Let's go back to 12, 9 sorry about that. You said you recognize Exhibit 10 12? 11 A. Yes, I do. 12 Q. Tell me what it is? 13 A. This would be my trip report 14 regarding the American Psychiatric Association 15 meeting of 1989, and I believe held in 16 California, in San Francisco, I believe. 17 Q. Second paragraph, the first 18 page, you talk about Doctor Blank, the 19 psychiatrist in blank who has attempted to obtain 20 use patents on Prozac for every psychological 21 malady known to man. Is that Doctor Nardon? 22 A. Yes, it is. 23 Q. Do you know if Doctor Nardon 24 did write a review of Prozac for the Harvard Page 399 1 Mental Health Letter? 2 A. I'm virtually certain I have 3 seen that, I subscribe to it. 4 Q. Do you know if that article 5 was critical of Prozac in any way? 6 A. I don't recall the contents. 7 Q. Is Doctor Nardon an associate 8 of Doctor Teicher's, to your knowledge? 9 A. Not to my knowledge. 10 Q. Did Doctor Nardon ever talk to 11 you about Doctor Teicher's article before the 12 article came out in February of 1990? 13 A. Not that I am aware of. 14 Q. It says here that Doctor 15 Nardon approached you and indicated that another 16 doctor, whose name is not disclosed here, 17 believed that he saw at least five patients, 18 inpatients where Fluoxetine induced suicidal 19 ideation, correct? 20 A. That's correct. 21 Q. And that that suicidal 22 ideation was more severe and pressing than 23 anything he had ever seen, correct? 24 A. That's correct. Page 400 1 Q. Is this Doctor Teicher here or 2 is this somebody else? 3 A. I believe that it is someone 4 else. With the blanking out -- may I comment? 5 MR. MYERS: Well, if you can answer 6 her question, answer it. 7 A. The name that was given to me 8 was either -- I don't recall whether it was Neppe 9 or Teppe, I believe it was Neppe. This 10 individual did not apparently work at Harvard as 11 best as we can track down and we filed a 1639 12 based on this report, we also found reports from 13 a doctor, I believe Doctor Neppe is the correct 14 name, in Washington, who had reported events that 15 appeared comparable to these. 16 Q. All right, reported them to 17 where? 18 A. Reported them to Lilly. 19 Q. Prior to this meeting you had 20 with Doctor Nardon? 21 A. I don't recall the precise 22 time between the 1639s and the 1639 that I filed 23 based on this. 24 Q. How do you spell Neppe? Page 401 1 A. I believe it's N-E-P-P-E. 2 Q. It says here according to, I'm 3 assuming that's Doctor Nardon, Doctor Neppe has a 4 case report in press. Does that refresh your 5 recollection? 6 A. Apparently that case report, 7 apparently Doctor Nardon was in error because I 8 am not aware of that ever coming to light. It 9 could have been speaking of Doctor Teicher but I 10 don't believe -- 11 Q. It's hard to tell with all the 12 blanks in this, right? 13 A. Again, because we track down 14 somebody with a very similar name in the same 15 location where he practices and he's not 16 associated with Harvard,. 17 Q. To your knowledge, is Doctor 18 Neppe associated with Doctor Teicher in any way? 19 A. No, I'm not aware of any 20 association. 21 Q. To your knowledge, are the 22 patients that Doctor Nardon was talking about 23 here, were these Doctor Teicher's patients or the 24 same patients that Doctor Teicher was treating? Page 402 1 A. No, it's not my -- I wouldn't 2 know definitively but I believe they were 3 inpatients of a different doctor. 4 Q. Okay. You say, It should 5 probably be kept in mind that Doctor Nardon, I'm 6 assuming, may have many agendas. Do you see 7 that? 8 A. Yes. 9 Q. What did you mean by that? 10 A. As I said above, Doctor Nardon 11 was, at the time that he approached me, to my 12 understanding, engaged with in a legal dispute 13 with Lilly about a use patent. 14 Q. Did Doctor Nardon work for or 15 with any other manufacturer, drug manufacturer? 16 A. I'm not aware of relationships 17 that he might or might not have with other 18 manufacturers. And as I'm thinking, your 19 question implied perhaps that he did have a 20 working relationship with Lilly. 21 Q. No, any other -- no, I didn't 22 mean to imply that. Did he ever have a working 23 relationship with Lilly, to your knowledge? 24 A. Not that I'm aware of. Page 403 1 Q. You go on to say blank's 2 analysis of suicide attempts for the Germans 3 bears on the issue. Do you see that? 4 A. Actually not. 5 Q. That's not blank, I'm reading 6 the marked out parts into the sentence. 7 A. Joe's analysis of suicide 8 attempts for the Germans bears on the issue. 9 Q. Oh, yours isn't blacked out. 10 That was my next question. So when you say Joe, 11 that means Doctor Wernicke's analysis? 12 A. That's correct. 13 Q. And then you say, we will 14 reanalyze data as currently available. Did you 15 do that? 16 A. I cannot specifically recall 17 what we did based on this, based on this memo. I 18 cannot recall producing any formal systematic 19 analysis of reports over and above reviewing 20 Joe's report potentially looking at counts in the 21 clinical trial data base which would constitute a 22 form of analysis. 23 Q. You looked at counts of what? 24 A. Suicidal acts. Again I cannot Page 404 1 specifically recall having done that and clearly 2 I believe that I did not prepare any sort of 3 formal written statement regarding that. 4 Q. Okay. The meeting that you 5 attended occurred when? 6 A. You're referring to this? 7 Q. The ones reflected in this 8 exhibit. 9 A. That would have been sometime 10 prior to May 19th. At that time it always began 11 on Mother's Day, so -- 12 Q. Did the -- when is the APA 13 meeting held now? 14 A. It's now held two weeks later 15 than it used to be held, it starts next week. 16 Q. In the Spring of the year? 17 A. That's correct. 18 Q. Traditionally every year in 19 the Spring? 20 A. In May in many years. 21 Q. So this issue was raised by 22 Doctor Norden and Doctor Norden's conveying of 23 Doctor Neppe's information back in May of 1989? 24 A. That's correct. Page 405 1 Q. Six months before the Teicher 2 article came out, correct? 3 A. That's correct. 4 Q. It implies here, your memo 5 implies that you knew of the Germans' issue at 6 this time in May of 1989, correct? 7 A. That I knew of Doctor 8 Wernicke's analysis. 9 Q. It says here, Joe's analysis 10 of suicide attempts for the Germans bears on the 11 issue. 12 A. That's correct, I was aware 13 that he had prepared or initiated this analysis 14 specifically for the Germans. 15 Q. Do you know why, or did you 16 know why back then? 17 A. Did I know specifically why? 18 Q. Were you surprised when you 19 were told that the Germans had raised the 20 suicidality issue about five years before it was 21 raised here in the United States? 22 MR. MYERS: Wait a minute, let me 23 object to the form to the extent you're assuming 24 the two issues are one and the same. I don't Page 406 1 know that there's any testimony that they are. 2 Go ahead. 3 Q. You're aware that the German 4 government raised the issue of suicide and the 5 use of Fluoxetine back in 1984, correct? 6 A. I was aware that Joe had 7 prepared this analysis that would suggest that 8 the issue had been raised. 9 Q. By the German government? 10 A. That's correct. 11 Q. Were you surprised when you 12 found out that the German government raised the 13 issue of the use of Fluoxetine and related 14 suicidality back in 1984? 15 A. Could you read the question 16 back? 17 Q. I'll restate it. Did it 18 surprise you when you learned, either at the time 19 of this memo or around this period of time, that 20 the German government had raised the issue of 21 whether or not Fluoxetine causes suicidality in 22 people back in 1984? 23 A. Since I learned of Joe's work, 24 I assumed that there was a question about Page 407 1 suicidality. I didn't understand why the 2 question had been raised, nor was I surprised. 3 Q. Why didn't you understand why 4 the question had been raised? 5 A. Because I didn't have any 6 documentation of the initial question, all I had 7 was the report. 8 Q. Have you since seen 9 documentation of the initial question? 10 A. I think that I saw something 11 yesterday in an exhibit that related to it. 12 Q. Besides this deposition, 13 before this deposition, have you ever seen 14 anything that -- any documentation of the 15 questions raised by the German government? 16 MR. MYERS: Back in '84-85. 17 Q. At any time, the questions 18 raised by the German government in '84-85? 19 A. Not that I recall. Clearly 20 those are implicit in Doctor Wernicke's report. 21 Q. Did you ask to see the 22 documents that were collected with regards to the 23 questions raised by the German government back in 24 '84 and '85? Page 408 1 A. Over and above what I managed 2 to track down, which was Doctor Wernicke's report 3 and some additional correspondence that happened 4 to be in Doctor Dornseif's file, those were all 5 that I could find. 6 Q. Correspondence related to the 7 German issue of suicidality and the use of 8 Fluoxetine? 9 A. Related to the analysis that 10 was conducted. 11 Q. Other than Doctor Wernicke's 12 report and the correspondence that you found in 13 Doctor Dornseif's files, have you seen any other 14 documentation related to the German government's 15 request for information regarding Fluoxetine and 16 suicidality in 1984? 17 A. The document that I saw 18 yesterday relates to that. 19 Q. Other than that document and 20 the stuff that you found in Dornseif's file or 21 Doctor Wernicke's analysis, anything else? 22 A. Not that I recall. 23 Q. Did you ask anybody to provide 24 you with any more information about the German Page 409 1 question? 2 MR. MYERS: When? 3 Q. When you started working on 4 your meta-analysis. 5 A. No. 6 Q. How about before that? 7 A. As I recall, again I had come 8 up, and again I believe from Doctor Dornseif's 9 file, a letter related to this. I presume from 10 that that I made inquiries in order to come up 11 with the two separate documents, one, a longer 12 one in this letter that I recall. 13 Q. What did Doctor Dornseif's 14 letter discuss? 15 A. I believe it discussed the 16 methodology used in the assessment and the 17 conclusions that were reached in this report. I 18 ultimately viewed them as complementary 19 documents. 20 Q. Were you aware before 21 yesterday that Lilly had hired an outside 22 consultant to review data on suicidality to 23 answer the Germans' initial question about 24 suicidality, in '84? Page 410 1 A. I was aware that outside 2 consultants did participate in Doctor Wernicke's 3 analysis, yes. 4 Q. Did you ever ask to see their 5 reports? 6 A. In fact I believe that the 7 letter that I'm referring to was in fact from 8 them and I believe that they were in part authors 9 on the physical document that I'm referring to as 10 Doctor Wernicke's report. 11 (PLAINTIFFS' EXHIBIT NO. 14 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Doctor I'm not going to ask 15 you anything specific about the report. You can 16 go ahead and finish reviewing it if you want. Is 17 this the report that Doctor Wernicke put 18 together, his analysis? 19 A. If I recall the documents 20 correctly, this appears to be a part of what I 21 was referring to. This is not the original 22 documentation in the form of the letter. 23 Q. Okay. This is the document 24 that you were referring to as the Wernicke Page 411 1 analysis and there is another document that you 2 found in Doctor Dornseif's file that was a letter 3 that he had written related to this analysis? 4 A. I believe it would have been 5 actually written to him. 6 Q. To Doctor Dornseif? 7 A. I believe so. Anyway it was 8 in Doctor Dornseif's file, I'm sorry. 9 (PLAINTIFFS' EXHIBIT NO. 15 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 Q. Okay. Go ahead and take a 13 look at that. 14 A. I assume I need to read. 15 Q. Before we get started, let me 16 ask you something real quick on this. Is this 17 the letter that you found in Doctor Dornseif's 18 file? 19 A. No. This, I am -- there are 20 apparently a couple of things stapled together 21 here. 22 Q. Okay. How about this first 23 portion that is Pz 2441 1998 through Pz 2441 24 2005? Page 412 1 MR. MYERS: What about it? 2 Q. This first portion of the 3 exhibit, is this the letter that you found in 4 Doctor Dornseif's file? 5 A. I do not believe it is. I 6 believe this is part of what I consider to be the -- 7 when I first saw the document, part of the 8 Wernicke report. 9 Q. How about this second half 10 that starts with Pz 2441 2006? 11 A. With -- I believe that there 12 was a different, shorter document that I obtained 13 from Doctor Dornseif's files to Doctor Dornseif. 14 I could be in error on that. 15 Q. Okay. 16 A. This latter attachment clearly 17 was addressed to -- was clearly signed by Doctor 18 Dornseif as opposed to being addressed to him. 19 Q. Okay. Do you recall seeing 20 this second half of this exhibit, the letter -- 21 draft letter dated July 18th, 1985 prior to 22 today? 23 A. I believe that I would have, 24 but I'm not absolutely certain that I did. Page 413 1 Q. Okay. I'm sorry, were you 2 done? 3 A. Yes. 4 Q. Approximately how much 5 volumewise documentation did you see related to 6 the German issue once you became aware of Doctor 7 Wernicke's analysis? 8 A. I have a recollection of this 9 document. 10 Q. Which exhibit is that? 11 A. Fourteen. As being in a 12 glosseen covered binder probably with this in it 13 as well. So -- and it was on thicker paper. 14 Q. So it was thicker than the 15 document that is marked Exhibit 14? 16 A. But I'm not sure that it was 17 any less than what is here contentwise. 18 Q. You mean anymore than what is 19 here contentwise? 20 A. Anymore than what is here 21 contentwise, or I believe its equivalent. I 22 believe that this was contained in there as well. 23 Q. The first portion of Exhibit 24 15? Page 414 1 A. Yes. This might or might not 2 have been contained in there. This might have 3 been made available to me through Doctor 4 Dornseif's files. And again, although I could be 5 in error, I believe I also at some point saw a 6 letter to Doctor Dornseif. 7 Q. Okay. Dated around the same 8 period, to your knowledge? 9 A. Through this period, clearly 10 all related to this analysis. 11 Q. Okay. Is it your 12 understanding that Doctor Weneker participated in 13 the analysis or at least reviewed the analysis of 14 the data for the German question? 15 A. That was my understanding. 16 Q. To your knowledge, is this 17 letter that -- the first portion of Exhibit 15, 18 is that a letter authored by Doctor Weneker? 19 A. I believe that he would have 20 been one of the three authors of this letter. 21 Q. Do you know who the other two 22 authors of the letter was? 23 A. No, I do not. 24 Q. Do you know if Doctor Fawcett Page 415 1 was used as a consultant on this issue back in 2 1985, the German issue? 3 MR. MYERS: Whether he was used or 4 whether he's one of these people? 5 MS. ZETTLER: Either one. 6 A. I don't know whether he was or 7 was not used. 8 Q. How about Doctor Dunner? 9 A. I don't know whether he was or 10 was not used. 11 Q. Do you recall generally who 12 Lilly used as consultants with regards to 13 Fluoxetine or psychiatric issues outside the 14 company back in this period of time, if you ever 15 knew? 16 MR. MYERS: On any issue? 17 MS. ZETTLER: You know, like the 18 psychiatric board or panel, advisory panel that 19 was established. Just generally who would be 20 used in the early days of the development of and 21 testing of Prozac outside the company as 22 consultants. 23 A. Quite frequently it would have 24 been the early board members I would presume. Page 416 1 But I have no specific knowledge of who would 2 have been frequently used. I'm not even sure 3 when the external advisory panel was first 4 brought into being. I believe it existed when I 5 joined Lilly. 6 Q. Have you ever heard the term 7 opinion leader? 8 A. Yes, I have. 9 Q. What is your understanding of 10 what the term opinion leaders means? 11 A. These are individuals, very 12 prominent and respected in the psychiatric -- 13 well, in the -- in a specific medical field. 14 Opinion leaders in psychiatry would be prominent 15 people whose opinions are respected. 16 Q. Who decides whether or not 17 these people that are opinion leaders are 18 prominent and respected in their field? 19 A. A number of individuals could 20 make that -- make that determination. That is a 21 term which is to my way of thinking used rather 22 loosely to refer to many individuals in a given 23 field. It doesn't have any special significance 24 in terms of a relationship with Lilly. So I Page 417 1 might refer to someone as an opinion leader, 2 someone in regulatory might refer to someone as 3 an opinion leader, there's no hard and fast 4 established criteria. 5 Q. Is that a phrase coined by 6 Lilly, opinion leader? 7 A. Lilly individuals use it. I'm 8 not sure whether it was coined by Lilly or 9 whether or not other people industry or 10 non-industry would use it. 11 Q. Have you ever heard anybody 12 outside of Lilly besides the opinion leaders 13 themselves using the phrase? 14 A. I can't recall hearing that 15 used by other individuals. 16 Q. Had you heard or used the 17 phrase prior to working at Lilly? 18 A. No. 19 Q. Does anybody at Lilly make a 20 determination as to whether a person in a 21 particular field such as psychiatry is going to 22 be considered an opinion leader for purposes of 23 say a seminar or any other programs conducted by 24 Lilly? Page 418 1 A. Yes. If -- and again, my 2 emphasis would be on the participation as such, 3 as an example on an advisory panel. 4 MS. ZETTLER: I'm sorry, can you read 5 that back? I spaced out. 6 (ANSWER READ) 7 MS. ZETTLER: So that was when I came 8 out of my coma. 9 Q. So if they were on one of your 10 advisory panels they would be considered an 11 opinion leader? 12 A. Yes, by definition. 13 Q. Okay. Would Doctor Teicher 14 ever have been considered an opinion leader by 15 Eli Lilly? 16 A. It's an interesting question 17 because I haven't ever thought of it. 18 Q. You haven't ever thought of 19 whether or not Doctor Teicher would be considered 20 an opinion leader? 21 A. Again, my sense is that the 22 people that have been selected to act as advisors 23 to Lilly, have come with somewhat more senior 24 academic credentials than Doctor Teicher. Not in Page 419 1 any way to demean Doctor Teicher's credentials. 2 MR. SMITH: You mean they're older. 3 THE WITNESS: Older and they've 4 published a few more papers and they get words 5 taken off the front of their titles. 6 Q. (BY MS. ZETTLER) Words taken 7 off the front of their titles? 8 A. You know, assistant and 9 associate, in general. 10 Q. So when you went from 11 assistant clinical research physician to a 12 clinical research physician you're getting up 13 there as far as more experience? 14 A. That was a promotion. 15 MS. ZETTLER: Do you want to take a 16 break? 17 MR. SMITH: That'll be fine. 18 (A SHORT RECESS WAS TAKEN.) 19 Q. (BY MS. ZETTLER) Doctor, 20 right before the break, you mentioned that you're 21 going to the APA convention, correct? 22 A. That's correct. 23 Q. Where is it being held this 24 year? Page 420 1 A. Philadelphia. 2 Q. Are you presenting a paper? 3 A. Yes, I am. 4 Q. Is the paper related to 5 Fluoxetine? 6 A. No, it's not. 7 Q. What's it on? 8 A. It's on an investigational 9 compound. 10 Q. What compound? You're 11 presenting it at the convention so I wouldn't 12 worry about it being a trade secret. 13 A. I got chastised yesterday, 14 actually by Mister Smith, for mildly, I think, 15 for revealing a name of an investigational 16 compound. 17 Q. Right, but that was in the 18 context -- you're going to present it at a APA 19 convention, you can tell us what it is. 20 MR. MYERS: Tell her what the 21 therapeutic class is. Let's not get sidetracked 22 on -- you can tell her what the therapeutic class 23 of drug is. 24 A. It's a potential Page 421 1 antipsychotic. 2 Q. Is it a seratonin reuptake 3 inhibitor? 4 A. No, it's not. 5 Q. Anything else that you're 6 presenting? 7 A. No. 8 Q. Is Doctor Tollefson's paper 9 going to be presented at that meeting? 10 MR. MYERS: Which one? 11 Q. That's a good question. The 12 analysis of -- that we were talking about 13 yesterday. The reanalysis of the clinical trial 14 data based on your article and the analysis of 15 agitation related to suicidality. 16 A. I guess I would like to use 17 the word activation. 18 Q. Okay, that's fine. 19 A. I'm not aware that that is 20 going to be presented as a paper. 21 Q. Is it going to be presented at 22 all? 23 A. It's -- I'm not aware that 24 that's going to be presented or discussed in any Page 422 1 way at the APA. 2 Q. Do you know why not? 3 A. My understanding is that it in 4 fact is in press. 5 Q. Isn't it common for papers to 6 be presented as posters or in other means at 7 conventions and seminars before it comes out in 8 press? 9 A. That's not uncommon, but I 10 don't have a good sense of how many papers -- 11 what percentage are first presented in verbal or 12 poster form. Certainly some percentage is. 13 Q. It does happen? 14 A. Yes, it does happen. 15 Q. And it's not rare? 16 A. No. But clearly a lot that 17 aren't as well. 18 Q. So I mean other than -- is 19 there any reason other than the fact that the 20 article is in press, Doctor Tollefson's article 21 is in press, is there any reason why it's not 22 being presented at the APA meeting, this year's 23 APA meeting? 24 A. None that I am aware of. Page 423 1 Q. Any Fluoxetine seminars that 2 you know of that are going to be presented this 3 year at the APA meeting, on depression? 4 A. I haven't seen a program. 5 Lilly is sponsoring symposia, I'm not sure 6 they're specifically related to Fluoxetine. 7 Fluoxetine may be discussed and other people 8 independent of Lilly may be presenting data on 9 Fluoxetine. I have not seen the program. 10 Q. To your knowledge, is Doctor 11 Fawcett speaking at the APA on behalf of Lilly or 12 any of Lilly's symposia this year? 13 A. I don't know specifically 14 whether he is or is not. 15 Q. How about Doctor Dunner? 16 A. I don't know specifically 17 whether he is or is not. 18 Q. Do you know of any outside 19 consultants or investigators that have been used 20 on Fluoxetine that are speaking at this year's 21 APA convention on Fluoxetine? 22 A. I don't know specifically if 23 they are or are not. 24 Q. Okay. Let's go back to Page 424 1 Exhibit 12. I believe it was your testimony 2 earlier that the study you mentioned here of 3 personality disorders suicide attempters, 4 specifically addresses the issue of suicidality 5 and the use of Fluoxetine, correct? 6 A. Yes. 7 Q. And you also mentioned here as 8 does abstract NR358, do you see that? 9 A. Yes. 10 Q. Does this refresh your 11 recollection as to what abstract NR358 is? 12 A. No, it does not. 13 Q. What is a -- have you seen 14 that designation before? Not necessarily 15 specifically NR358, but an abstract being 16 designated as a number? 17 A. Yes. 18 Q. What is that, if you know? 19 A. That refers to new research 20 then and that's a category of presentation at the 21 APA. And then 358 is simply the number of the 22 abstract either to be presented as a poster or a 23 limited number of research if research is 24 presented orally, and it's the 358th of x-number. Page 425 1 Q. Is that a designation made by 2 the APA or is that a designation made by Lilly? 3 A. That's a designation made by 4 the APA in their abstract book. 5 Q. Would you have a copy or would 6 there be a copy of that NR358 still in existence 7 at Lilly today? 8 A. I would not know if there is 9 or is not. 10 Q. Do you know if NR358 was an 11 abstract of a paper that was written by Lilly or 12 something that was presented by Lilly? 13 A. With a reasonable degree of 14 certainty, I believe I can speculate that this 15 was something that was independent of Lilly. 16 Q. Is it your belief that NR358 17 addressed the issue of suicidality and the use of 18 Fluoxetine? 19 A. It would have -- from my memo, 20 it would appear that at the time, I clearly 21 believed that it had some relevance to the issue. 22 Q. Could NR358 be an abstract of 23 Doctor Montgomery's study results? 24 A. From the syntax of the Page 426 1 sentence, I don't believe that it is. 2 Q. To your knowledge, has Doctor 3 Montgomery's study, the results of his study ever 4 been published? I'm talking about the 5 personality disorder, suicide attempter study 6 that you refer to here. 7 A. I don't recall if it has or 8 has not been published in journal article format. 9 Q. Do you recall whether it's 10 been published in any format? 11 A. It may have been presented and 12 therefore published as an abstract. I'm not 13 entirely certain about that. 14 Q. You mean like at an APA 15 committee? 16 A. Right. Or some other meeting. 17 Q. To your knowledge, were the 18 results of Doctor Montgomery's personality 19 disorder suicide attempters study presented to 20 the drug advisory committee that was convened in 21 September of 1991? 22 A. I don't recall with certainty 23 whether or not any data from that study was 24 included in the report that went to the FDA. Page 427 1 Q. To your knowledge, has a final 2 report on Doctor Montgomery's study ever been 3 submitted to the FDA? 4 A. I am not aware of such report 5 being submitted. 6 Q. Why not? 7 A. I'm not sure a final report 8 has been prepared at this time or not. 9 Q. Do you know when Doctor 10 Montgomery's study was completed? 11 A. I'm uncertain when it was 12 completed. 13 Q. Do you know when it was 14 started? 15 A. I have a fair idea of when it 16 was started in that it would probably have been 17 sometime in 1988. 18 Q. Okay. Do you know if it was 19 completed as of the date of this exhibit, May 20 19th, 1989? 21 MR. MYERS: When you say completed, 22 what do you mean? 23 MS. ZETTLER: Well, finished. 24 MR. MYERS: You mean the last patient? Page 428 1 Because he said he didn't know if there was a 2 report. That's why I asked. 3 MS. ZETTLER: No, he said he didn't 4 believe that a report had been prepared. 5 Q. Yes, last patient, we'll use 6 that. 7 A. I believe that the time for 8 individual patient participation was rather 9 lengthy, probably a year, and it may not have 10 been completed at the time this report was 11 prepared, this report. 12 Q. Do you know if it was 13 completed before January of 1990? 14 A. No, I do not. 15 Q. It was completed before the 16 Advisory Committee Meeting in 1991, was it not? 17 A. It may have been completed, I 18 believe that it was but I am not absolutely 19 certain. 20 Q. Doctor Montgomery was a 21 consultant to that committee in 1991, at least 22 during that meeting, was he not? 23 A. I am uncertain of the 24 membership of the committee. I was not in Page 429 1 attendance at that meeting. 2 Q. Why not? 3 A. My mother was having open 4 heart surgery and I was in Lexington. 5 Q. Okay. 6 Q. If Doctor Montgomery's study 7 results or study in general were not discussed 8 during the 1991 Advisory Committee Meeting, do 9 you know why it would not have been? 10 A. No. 11 Q. Do you think it should have 12 been? 13 A. I think it would have been 14 appropriate to do so, but not necessarily 15 absolutely mandatory. 16 Q. Do you think it would have 17 been relevant to the issue? 18 A. I believe that it is relevant 19 to the issue. 20 Q. And you have no idea or you 21 know of no reason why it would not be presented? 22 A. No. 23 Q. What were the results of 24 Doctor Montgomery's study? Page 430 1 A. As I understand them, 2 recalling conversations with Doctor Montgomery 3 and not being able to recall reading a manuscript 4 or an abstract, I believe that his findings were 5 in essence neutral, that Fluoxetine did not 6 reduce the rate of suicidal, or what he might 7 have referred to as parasuicidal acts in a 8 personality disorder population. 9 Q. Fluoxetine did not decrease 10 suicidal rate or parasuicidal rate, is that what 11 you said in Fluoxetine patients? 12 A. Relative to placebo, there was 13 not a statistically significant reduction in the 14 rate of these acts or gestures relative to 15 placebo. 16 Q. How about increase relative to 17 placebo? 18 A. I don't believe that that was 19 the case. And I believe there was no statistical 20 significance difference. 21 Q. Was there another comparator 22 used in that? 23 A. Placebo, I believe, was the 24 only comparator. Page 431 1 Q. Do you know if concomitant 2 administration of benzodiazepines or hypnotics 3 was allowed in that study? 4 A. I don't recall specifically. 5 Q. Do you know if it was an 6 inpatient or outpatient study? 7 A. As I recall, this was an 8 outpatient study. In some extent, I infer that 9 from my belief that this was necessarily a long 10 term, one year study. 11 Q. Was that a study that was paid 12 for by Lilly? 13 A. I believe it was sponsored by 14 Lilly. 15 Q. What do you mean when you say 16 personality disorder patients? 17 A. These patients had to suffer 18 from a personality disorder, which means that 19 they had to have a DSM3 or 3R at the time, I 20 forget which was relevant, Axis 2 diagnosis. 21 This is -- makes a distinction between 22 personality disorders or now longstanding 23 developmental disorders on Axis 2 versus more -- 24 the distinction is -- on Axis 1 are the disorders Page 432 1 which are frequently episodic in nature or may 2 have long -- late onset, as contrasted to those 3 disorders that are placed on Axis 2 in 4 personality disorders and developmental disorders 5 which are thought to be the psychiatric diagnoses 6 that one evolves from early childhood. 7 Q. Were these people suffering 8 from depression? 9 A. I don't believe depression was 10 an exclusionary criteria. They did not 11 necessarily have to be suffering from depression. 12 Q. Why don't you try and give me -- 13 like, for instance, bipolar, try to give me a 14 layman's term for what these people would be 15 known as? 16 A. Have you heard the term 17 borderline? 18 Q. Yes. 19 A. That's a personality disorder 20 that's actually frequently associated with 21 suicide attempts. 22 (OFF-THE-RECORD DISCUSSION) 23 A. Basically, personality 24 disorders are defined as longstanding chronic Page 433 1 maladaptive ways of relating to self, others, or 2 the world. 3 Q. Okay. 4 A. And their traits -- they move 5 from traits to disorders when they are sufficient 6 to cause significant distress, either the person 7 suffering from it or to other people. 8 Q. Could these people be a threat 9 upon -- to themselves or others? 10 A. They might or might not be. 11 Q. To your knowledge, was Joseph 12 Wesbecker ever diagnosed as borderline? 13 A. I am not familiar with Mister 14 Wesbecker's potential Axis 2 diagnosis. 15 Q. Could somebody 16 schizo-affective be borderline? 17 A. There is no absolute 18 exclusionary rule to diagnosing somebody with the 19 Axis 1 disorder that you mentioned, 20 schizo-affective disorder, and borderline 21 personality disorder. 22 Q. When did you discuss the 23 Montgomery study with Doctor Montgomery? 24 A. I don't recall specifically. Page 434 1 Q. Was it before or after the 2 1991 Advisory Committee Meeting? 3 A. I'm sorry, I just can't recall 4 when. 5 Q. Have you discussed it with him 6 on more than one occasion? 7 A. I may have. 8 Q. When you discussed the study 9 with Doctor Montgomery, was this in person or was 10 this like over the phone? 11 A. I think it was probably on an 12 occasion when I had seen Doctor Montgomery. 13 Q. Here or in the UK? 14 A. Probably at a meeting that 15 would have likely been a U.S. meeting since at 16 this time I attended U.S. meetings and almost no 17 international meetings. 18 Q. Do you know why a final report 19 has not been written on Doctor Montgomery's 20 study? 21 A. Again, perhaps I should 22 correct myself. I don't know specifically if a 23 report has or has not been prepared on that 24 study. Page 435 1 Q. Do you know if a study was 2 completed before the 1991 committee meeting as 3 far as the last patient having been treated? 4 A. I believe that it had been. I 5 cannot be absolutely certain. 6 Q. Is it typical or common for a 7 final report on a study to not have been written 8 approximately three years after the completion of 9 the study as far as the patients are concerned? 10 A. It may depend upon the nature 11 of the study. There are studies which probably 12 go longer before final reports are completed. 13 That may be even more the case with European 14 studies. But there is a substantial variance in 15 the time from last patient completing, last visit 16 through the production of a final report. 17 Q. Do you know where Doctor 18 Montgomery got his patient pool from for that 19 study? 20 A. No. As I said, I believe the 21 study was conducted in the UK. 22 Q. Do you know why Lilly wanted 23 that study conducted? 24 A. I don't know the specific Page 436 1 reasons why Lilly agreed to sponsor that study. 2 Q. Do you know if Doctor 3 Montgomery raised the issue of performing this 4 study or if that was an issue raised by Lilly? 5 A. I don't know. I know that 6 this is an interest of Doctor Montgomery's. 7 Q. Has he done any other studies 8 either sponsored by Lilly or not, regarding the 9 use of Fluoxetine and suicidality? 10 A. I'm not aware of any other 11 studies that he has done specifically dealing 12 with suicidality and Fluoxetine. 13 Q. From your discussion or 14 discussions with Doctor Montgomery on the study, 15 did he mention anything unusual about the study, 16 any patient behavior that was unusual, anything 17 of that nature? 18 A. I don't recall that. 19 Q. Did he say anything about 20 violent aggressive behavior on that study? 21 A. None that I recall, no. 22 Q. To your knowledge, has Lilly 23 ever conducted a study on the use of Fluoxetine 24 on patients suffering from schizo-affective Page 437 1 disorders? 2 MR. MYERS: In order to treat it or 3 for what? 4 MS. ZETTLER: For anything whatsoever, 5 whether they've conducted any studies on patients 6 suffering from schizo-affective disorders using 7 Fluoxetine. 8 A. Specifically? 9 Q. Yes. 10 A. So that that would be the only 11 diagnosis? 12 Q. Something that was the main 13 diagnosis, let's put it that way. 14 A. Not in the United States and I 15 very seriously doubt in Europe. 16 Q. Why not? 17 A. The -- I don't know why not. 18 Q. Why do you say you very 19 seriously doubt in Europe? 20 A. I don't have a sufficient 21 knowledge of all protocols conducted throughout 22 the world, particularly in Europe, especially in 23 Europe, to be absolutely confident in my 24 response. But again, I would doubt it and that's Page 438 1 based on my perception that routine treatment of 2 schizo-affective patients involves multiple 3 medications, not just an antidepressant. 4 Q. Do you have any reason to 5 believe that the use of Fluoxetine would be 6 contraindicated in schizo-affective patients? 7 MR. MYERS: To treat what? 8 MS. ZETTLER: Either the depressive 9 element or the schizo-affective disorder or any 10 other element of the disorder. 11 A. You're asking me to make a -- 12 Q. Generally. 13 A. -- give an opinion sort of 14 over the whole population as opposed to specific 15 patients? 16 Q. Right, generally. 17 A. Under -- again, under 18 appropriate circumstances which would be 19 individually tailored, no. 20 Q. Besides Doctor Montgomery's 21 study on using Fluoxetine in personality disorder 22 suicide attempters, do you know of any other 23 studies that have been conducted either by Lilly 24 or on behalf of Lilly to investigate the issue of Page 439 1 Fluoxetine and suicidality or Fluoxetine and the 2 treatment of suicidality? 3 A. Again, just specifically 4 address suicidality? 5 Q. Where it's at least one of the 6 main objectives of the study. 7 A. I can't recall any. 8 Q. Do you know of any studies -- 9 such studies that are planned currently? 10 A. No. 11 Q. How about violent aggressive 12 behavior, are you aware of any studies that have 13 been performed by Lilly or on behalf of Lilly 14 where one of the main objectives was to 15 investigate the relationship between the use of 16 Fluoxetine and the occurrence of violent 17 aggressive behavior? 18 A. I'm not aware of such studies. 19 Q. Are you aware of a 20 post-marketing surveillance and suicidal thought 21 study that was conducted in South Africa by 22 Lilly? 23 A. As you mention that, I recall 24 a post-marketing surveillance. Page 440 1 Q. Okay. Tell me what you recall 2 about it. 3 A. That it was, in fact, 4 something that was reported. Now that you 5 mention it to me, I think I can recall a couple 6 of grafts out of a report, again I could be 7 incorrect in this recollection, but I think I 8 recall seeing some 2 Axis grafts and some lines 9 coming down on the grafts. 10 Q. When was that study conducted? 11 A. I don't recall. 12 (PLAINTIFFS' EXHIBIT NO. 16 WAS 13 MARKED FOR IDENTIFICATION AND 14 RECEIVED IN EVIDENCE.) 15 Q. Okay. Do you recognize this 16 exhibit? 17 A. I believe that I have seen 18 certain parts of this, probably all, as I recall 19 these grafts. 20 Q. Okay. Can you tell me what Pz 21 number page that is? 22 A. I used as an example Pz 541. 23 Q. Okay. 541 what? 24 A. Excuse me, 562. Page 441 1 Q. So these grafts towards the 2 end of the report, you have seen at least some of 3 them? 4 A. I believe that I have, yes. 5 Q. Before I forget, who was the 6 medical monitor on Doctor Montgomery's study? 7 A. I'm not certain as that was a 8 European study. 9 Q. Do you know which affiliate 10 would have been in charge of that? 11 A. I believe that would have been 12 the UK. 13 Q. Do you know if it's Erl Wood 14 or Basingstoke? 15 A. I don't know which. 16 Q. One of those two? 17 A. Yes. 18 Q. Do you know if the marketing 19 department paid for that study, the Montgomery 20 study? 21 A. I don't know. 22 Q. How come Doctor Montgomery's 23 study wasn't included in your meta-analysis? 24 A. The meta-analysis was looking Page 442 1 specifically at depression, for one thing. Given 2 that it was a European study, we did not have 3 that data available to us when that meta-analysis 4 was performed. 5 Q. You said that the 6 meta-analysis was looking specifically at 7 depression? 8 A. At studies that involved 9 unipolar or in one case bipolar depression as the 10 primary diagnosis. 11 Q. Why did you include the 12 bipolar depression study in your analysis? 13 A. Because we felt that it was, 14 in fact, relevant in that the patients had to 15 present with depression. 16 Q. But they also had to present 17 with bipolar depression, did they not? 18 A. That would be a history of one 19 or more manic episodes in the past, but the 20 presenting symptomatology would be comparable. 21 Q. Is that a pilot study? 22 A. I did not conduct and I was 23 not here when that study was conducted. Whether 24 or not that was considered a pilot -- it might Page 443 1 have been considered a pilot if there were plans 2 to do, again, larger or additional studies. I 3 don't know if that was the case or not. 4 Q. Would you have objected if it 5 was a pilot study? 6 MR. MYERS: Object to what at what 7 point in time? 8 MS. ZETTLER: Including it in the 9 meta-analysis. 10 A. No. 11 Q. Why not? 12 A. Because it met the criteria 13 for being double-blind placebo controlled and 14 patients were depressed at baseline. The -- what 15 we referred to as cross sectional symptomatology 16 at presentation was comparable to the other 17 studies. 18 Q. So as long as it was a 19 depression study that was double-blind 20 controlled, it didn't matter to you, at least, 21 whether or not it was a pilot study or a regular 22 clinical trial? 23 A. Well, I'm not aware of any of 24 these trials being considered or being labeled as Page 444 1 pilots. 2 Q. That study, the bipolar study 3 that you included was a study conducted by Doctor 4 Cohn, correct? 5 A. I am -- 6 Q. You can refer back to the 7 exhibit if you like. 8 A. My copy is sort of -- 9 Q. If you look at page 692, in 10 the upper right-hand corner. 11 MR. MYERS: Looking at the page which 12 way? 13 MS. ZETTLER: I'm sorry, if you hold 14 the page vertically. 15 A. Yes. Again, my copy is pretty -- 16 Q. Can you read it, I mean mine -- 17 I don't know if mine is much better. 18 A. It's Doctor Cohn. 19 Q. Okay. How many studies, to 20 your knowledge, did Doctor Cohn do for Lilly on 21 Fluoxetine and depression? 22 A. I am uncertain of the number 23 of studies on which he was either an investigator 24 or a sub-investigator. Page 445 1 Q. Can you give me an estimate of 2 how many, more than ten? 3 A. I seriously doubt it. 4 Q. Okay. More than five? 5 A. Possibly, I doubt it. 6 Q. Possibly, but you doubt it? 7 A. I doubt it, again -- 8 Q. Back to Exhibit 16. This says 9 this exhibit is dated September 19th, 1988, 10 correct? 11 A. That's correct. 12 Q. And this is a final report on 13 this, is it not? 14 A. That's correct. 15 Q. Okay. So this indicates to 16 you that this study was completed sometime before 17 September of '88, correct? 18 A. That's correct. 19 Q. Okay. Do you have any idea 20 when this study was started and how long it ran? 21 A. Let me look at something. 22 MR. MYERS: What was the question? 23 MS. ZETTLER: If he knows when the 24 study was started and how long it ran. Page 446 1 A. You know, I'm not. And what I 2 would like to point out if I may. 3 Q. Sure. 4 A. That it looks to my like this 5 is probably the face page for initial protocol. 6 Q. Okay. 7 A. And the actual report. 8 Q. Give me a page. No, I found 9 it. June 1st, 1990, correct? 10 A. That's correct. 11 Q. Okay. 12 A. So if I may, I believe, the 13 study was started after 19 September 1988. 14 Q. So it ran between -- sometime 15 between September 1988 and June of 1990, correct? 16 I mean obviously it had to be started after 1988. 17 A. If I'm correct in all of my -- 18 Q. If these dates are right and -- 19 A. If what I think these dates 20 represent. 21 Q. Okay. Did you have anything 22 to do with this study? 23 A. No. 24 Q. Were you involved in Page 447 1 discussions on whether or not this study should 2 be conducted? 3 A. Not that I recall. 4 Q. Do you know if anybody at 5 Lilly Indianapolis worked on that study either 6 directly or indirectly? 7 A. I don't have any knowledge of 8 that. 9 Q. Do you know why they -- Lilly 10 felt it necessary to run a Prozac 20 11 post-marketing surveillance on suicidal thoughts 12 study? 13 A. No, I don't. 14 Q. Was this study, to your 15 knowledge, discussed during the 1991 Advisory 16 Committee Meeting? 17 A. Again, not being in 18 attendance, I don't know if it was discussed at 19 that meeting. I am uncertain whether it was 20 discussed or included in the lengthy 21 presubmission or premeeting submission. 22 Q. How long was that submission 23 volumewise? 24 A. I remember it being a huge Page 448 1 volume. 2 Q. Can you give me an idea, 3 estimate? 4 A. We're talking in -- 5 Q. About a foot thick? 6 A. Well, fairly thick, not quite 7 a foot. 8 Q. Nine, ten inches thick maybe? 9 A. Six to -- I think it fit in 10 one huge volume. It may have been split in two. 11 Q. So it could have been fit into 12 one huge binder, but it may have been split into 13 two? 14 A. Possibly, again that's my -- 15 Q. That's all I'm asking for is 16 your recollection. 17 A. Right. 18 Q. Do you know if that volume or 19 two volume submission was made to each and every 20 committee member? 21 A. I am not sure of the process 22 by which the agency would have distributed 23 information for review to their advisors. 24 Q. Okay. Do you recall whether Page 449 1 or not the Montgomery study was mentioned in that 2 precommittee meeting submission? 3 A. I don't recall specifically. 4 Q. And you don't recall whether 5 or not this study report was submitted? 6 A. Discussed in that document, 7 no. It would be quite speculative. 8 Q. Do you know if this 9 statistical report that's attached as part of 10 Exhibit 16 was ever submitted to the FDA? 11 A. No, I don't. 12 Q. In what situations would Lilly 13 not have to submit a protocol to the FDA for 14 approval before conducting a study on its 15 protocol? 16 A. I am not sufficiently versed 17 in the regulatory requirements of protocol 18 submission, at least with respect to those 19 conducted outside the country, potentially not 20 under our IND. 21 Q. I'm not limiting it, I'm 22 talking here in the United States. Is there any 23 situation where if Lilly wanted to conduct a 24 study on Prozac that they would not have to Page 450 1 submit a protocol to the FDA for approval before 2 conducting that study? 3 A. My understanding is if it were 4 conducted under the U.S. IND, it would need to be 5 submitted, whether there are unique or special 6 circumstances -- and again, I'm giving you my 7 understanding which could be in error, if there 8 may be some unique and special circumstances 9 where a study could be conducted that was not 10 conducted under the IND, I don't believe so, but 11 I can't -- 12 Q. Let me make sure I understand 13 you. It's your understanding that if a study is 14 going to be conducted under the IND, a protocol 15 needs to be submitted to the FDA for approval? 16 A. That's correct. 17 Q. There may be some 18 circumstances that you are not aware of where you 19 could conduct an IND study and not have to submit 20 a protocol? 21 A. Where a study might be 22 conducted that would not be conducted under the 23 IND. 24 Q. So it could be an NDA study Page 451 1 where you would not have to submit a protocol? 2 A. The NDA, as I understand it, 3 has to do with approval to market the compound. 4 It's not an issue of performing a study. 5 Q. But information would be 6 submitted to the NDA after a drug has been on the 7 market, can it not? 8 A. Yes. We're now into a 9 regulatory domain about the distinctions of what 10 gets submitted to an IND versus an NDA versus 11 both that I do not have detail -- that I have no 12 knowledge of. 13 Q. Would a study -- if a study 14 like the one reflected in Exhibit 16, the 15 post-marketing surveillance study, were to be 16 conducted here in the United States, would the 17 protocol for this study have to be submitted to 18 the FDA, as far as you know? 19 A. Given that Fluoxetine was in 20 fact administered and that the study was being 21 conducted by Lilly, I believe that it would be 22 conducted under the IND and therefore submitted. 23 Q. Do you know if there are any 24 FDA requirements that studies that are conducted Page 452 1 outside the United States on protocols created 2 by, say, somebody here in Indianapolis at Lilly, 3 that that protocol needed to be submitted to the 4 FDA for approval? 5 A. I don't know if such 6 regulations exist or do not. 7 Q. How about final reports? 8 A. The same. 9 Q. Let me ask the question. 10 Final reports for studies conducted outside the 11 United States, like for instance Doctor 12 Montgomery's study, does the FDA require that 13 Lilly submit those to either the IND or the NDA 14 on a particular drug? 15 A. I don't know. 16 Q. How about studies done here in 17 the United States, if a study is done on a 18 protocol, for instance, that is submitted to the 19 IND and approved by the FDA, does a final report 20 on that study, regardless of the success of the 21 study, have to be submitted to the FDA? 22 A. I believe that is the case. I 23 am unaware of whether there are or are not 24 exceptions. Page 453 1 Q. Are you aware of any study 2 that has been performed by Lilly on Fluoxetine -- 3 or on behalf of Lilly on Fluoxetine where a final 4 report -- here in the United States, where a 5 final report has not been submitted to the FDA? 6 MR. MYERS: Under the IND? 7 Q. Under any study whatsoever. 8 A. That Lilly in some way 9 sponsored? 10 Q. Right. They developed a 11 protocol, they submitted it to the FDA. Okay, 12 you follow me so far? 13 A. Yes. 14 Q. The FDA approves the protocol? 15 A. Right. 16 Q. Then Lilly sets up a clinical 17 trial based on that protocol, pays for it, finds 18 the investigator, et cetera. 19 A. Right. 20 Q. Are you aware of any trial, 21 whatsoever, where that occurred where a final 22 report was not submitted to the FDA by Lilly? 23 A. I don't have any knowledge of 24 such, assuming that a -- that once the final Page 454 1 report was completed. 2 Q. What do you mean you don't 3 have knowledge of that once the final report was 4 completed? 5 A. I don't have any knowledge of 6 any final reports not being submitted once they 7 were completed. 8 Q. Are you aware of any trials 9 that were conducted in patients that were 10 completed through the trial where a final report 11 has not been completed? And I'm not talking 12 about -- I'm talking about a trial that, you 13 know, an inordinate amount of time between the 14 end of the trial and the analysis and the final 15 report being completed. 16 MR. MYERS: Let me object to the form 17 and the term inordinate because it's vague. I 18 think I understand what you're getting at, but I 19 still think it's kind of vague. 20 MS. ZETTLER: Did that come from you 21 or did that come from Mary? 22 MR. MYERS: She's helping me. 23 MS. ZETTLER: Amazing. 24 MR. MYERS: She's not writing me a lot Page 455 1 of notes like you are writing to Paul. 2 A. You're asking me if I -- let 3 me see if I can -- if I know of a study -- 4 Q. Let me ask it again. I think 5 what I'm getting confused on is you said a little 6 while ago you don't know of any study where a 7 final report has been written where that report 8 has not been turned into the FDA. Correct? 9 A. That's correct. 10 Q. What I'm trying to find out is 11 are there studies that you know of that were 12 started by Lilly and whether or not they were 13 completed, a final report was never written and 14 therefore never submitted to the FDA? 15 A. I'm not aware of any such 16 cases. 17 MS. ZETTLER: You want to take a 18 break? 19 MR. MYERS: Sure. 20 (A SHORT RECESS WAS TAKEN.) 21 Q. Doctor, why did you include 22 Doctor Cohn's study conducted under protocol 27 23 in your meta-analysis? 24 A. It was part of the data base. Page 456 1 Q. Are you aware that the FDA 2 decided not to take Doctor Cohn's study under 3 protocol number 27 into account in its review of 4 the studies done under protocol 27 in support of 5 efficacy because it was biased or too biased in 6 favor of Lilly or in favor of Fluoxetine? 7 MR. MYERS: I object to the form. 8 A. I am aware that that study was 9 submitted separately from the other investigators 10 which were combined in the NDA. I'm not certain 11 who made the decision to split that study, that 12 site out from the rest of the sites. 13 (PLAINTIFFS' EXHIBIT NO. 17 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 A. I have read this memo. 17 Q. Have you ever seen Exhibit 17 18 before? 19 A. No. 20 Q. Were you aware that in 21 November of 1984, the FDA or at least this group 22 of people at the FDA were concerned about flaws 23 in the design and execution of the Fluoxetine 24 studies, the main efficacy trials? Page 457 1 A. No. 2 Q. Did you ever become aware of 3 that fact? 4 A. Not until I have seen this 5 memo. 6 Q. This is a memo authored by 7 Tony De Cicco at the FDA, do you know Mister De 8 Cicco? 9 A. I don't know him personally, 10 no. 11 Q. Have you heard of him? 12 A. Yes. 13 Q. And you've heard that he is 14 the CSO on Fluoxetine at Lilly or at the FDA or 15 at least had been at one point in time? 16 A. Yes, he was one of several, I 17 believe. 18 Q. This appears to be a 19 recitation of meeting minutes held in-house at 20 the FDA between -- a meeting held between Doctor 21 Leber, Doctor Hayes, Doctor Lee, Doctor Laughren, 22 Doctor Kapit, Doctor Chi and Mister De Cicco, 23 correct? 24 A. That's correct. Page 458 1 Q. And the meeting is dated 2 November 13th, 1984? 3 A. That's correct. 4 Q. At the bottom of the first 5 paragraph, the last sentence says one strongly 6 positive study, and in parens it says Cohn, 7 closed paren, showed an extreme degree of this 8 differential dropout rate raising questions about 9 the results of the trial. Do you see that? 10 A. That's correct. 11 Q. Were you aware of that fact, 12 that Doctor Cohn's study was strongly positive? 13 A. Yes, I was. 14 Q. Were you aware that it showed 15 an extreme degree of differential dropout rate in 16 the study? 17 A. I'm less certain of 18 recollecting that at the time. I was very much 19 aware of the positive overall efficacy 20 difference. 21 Q. Would there have been another 22 Protocol 27 that was created by Lilly other than 23 the one that was submitted to the FDA in support 24 of efficacy? Page 459 1 A. I'm only aware of the 2 multi-center trial, one trial being conducted as 3 protocol 27. As to whether or not there were 4 amendments to that protocol, I don't know. 5 Q. Protocol 27, to the best of 6 your recollection, is the protocol under which 7 studies were conducted on Imipramine, placebo and 8 Fluoxetine, correct? 9 A. A study with multiple sites 10 participating, that's correct. 11 Q. As far as you know there is no 12 other protocol 27 out there that is a different 13 study? 14 A. No, I'm not aware of one. 15 Q. Are you aware that the 16 multi-center study that was conducted under 17 protocol number 27 was submitted to the FDA in 18 support of efficacy? 19 A. Yes, I was. 20 Q. You're just not aware of 21 whether or not Doctor Cohn's study was culled out 22 of the rest of the multi-centered studies 23 conducted under 27 by the FDA or by Lilly? 24 A. I have a belief about that Page 460 1 matter, but I am uncertain that that belief is 2 correct. 3 Q. What is your belief? 4 A. My belief is that that 5 decision was made by Lilly. But again, I want to 6 emphasize that I'm not certain about that. 7 Q. How do you come to that 8 belief? 9 A. I believe that I have -- I 10 believe that I recall statements to that effect, 11 in fact, made by Doctor Thompson and that he 12 could have been in fact a very significant 13 participant in making that decision to split that 14 out. 15 Q. Okay. If Doctor Cohn's study 16 was so strongly positive that Lilly decided to 17 split it up from the rest of the multi-center 18 studies, at least upon submitting it to the FDA, 19 why would you include it in the meta-analysis? 20 MR. MYERS: When you say the rest of 21 the multi-center, you mean the other centers for 22 that study? 23 MS. ZETTLER: Right, that's what I 24 mean. Page 461 1 A. Okay. Given that this was a 2 safety study analysis, it was clearly important 3 to look at the occurrence or lack thereof of 4 suicide attempts in his study. We had no reason 5 to believe that such adverse events, if they 6 existed, would or would not have been in any way 7 related to differential efficacy that he saw or 8 what's reflected in the minutes here. We also 9 had no reason to believe that the specific Ham-D 10 question related to suicide was in any way 11 differentially represented across his site versus 12 other sites. I would add that that was not an 13 analysis that was conducted to see if he showed 14 unusual characteristics relative to other sites 15 for that Hamilton item, but we had no reason to 16 believe that. 17 Q. Wasn't the Ham-D ratings the 18 main efficacy determinant in the studies? 19 A. That's correct. 20 Q. Okay. So if Doctor -- and I'm 21 assuming that by strongly positive meaning that 22 the Ham-D scores on Fluoxetine people compared to 23 placebo people or comparator people on Imipramine 24 were much lower for Fluoxetine than they were for Page 462 1 the other two comparators? 2 A. That's correct. 3 Q. Then why do you feel that the 4 Ham-D-3 rating wouldn't be affected by that lower 5 score? 6 A. Excuse me, but I think your 7 question just implied something that I didn't -- 8 Q. Maybe I misunderstood you. 9 A. What I stated, I believe, was 10 that we did not have knowledge that there was a 11 differential effect on that question. 12 Q. But you didn't go and try to 13 investigate it either, did you? 14 A. That's correct. 15 Q. Why not? 16 A. I don't have a reason why we 17 did not do that. 18 Q. Was it because it was 19 beneficial for you not to? 20 A. I cannot recall at any time 21 thinking that and, therefore, not analyzing it or 22 splitting it out separately. 23 Q. Would you have had a decision 24 in input into whether or not to include Doctor Page 463 1 Cohn's study in your meta-analysis? 2 A. Yes, I would. 3 Q. Why didn't you ask to have it 4 taken out of the meta-analysis or not consider it 5 in the meta-analysis? 6 A. I don't have any reason that I 7 did not. 8 Q. What makes you think that 9 Doctor Cohn wouldn't have been biased in his 10 reporting of adverse events related to Fluoxetine 11 or any other drug on this study if he was so 12 strongly biased in favor of Fluoxetine on the 13 efficacy side? 14 MR. MYERS: Let me object to the form 15 in the extent it assume that the Doctor himself 16 was biased in favor of something or the other. I 17 don't know that that's what any of the documents 18 says or what the testimony is so far. 19 Q. Do you have any other 20 explanation as to why Doctor Cohn's study would 21 be so strongly positive in favor of Fluoxetine 22 other than his bias in favor of the drug? 23 MR. MYERS: Same objection. Go ahead 24 and answer. Page 464 1 A. It could be, again, 2 occurrences in the world can be distributed 3 across a continuum, it could be real, it could be 4 a real effect that he had particularly unique 5 patients, that this was not an issue of any sort 6 of bias. I think what's being suggested here are 7 that there are potentially factors in the design 8 of the protocol that may have had particular 9 effects at Doctor Cohn's site. Not that -- 10 again, I don't read this to indicate that he was 11 biased in his ratings. That's not how I read 12 this. 13 Q. But the study was obviously 14 biased in favor of Fluoxetine? 15 A. What I believe I have said 16 with regard to Doctor Cohn's site is that bias of 17 some sort potentially designed interacting with 18 his particular -- or at his particular site, may 19 have had an impact on the overall efficacy 20 outcome of his study. 21 Q. For whatever reason that it 22 happened, the results of the study were obviously 23 biased in favor of Fluoxetine. 24 A. When you say biased, again, Page 465 1 I'm sorry, one alternative was that this was a 2 real finding at his site. His site was clearly 3 exceptional. 4 Q. The results of the study were 5 strongly in favor of Fluoxetine -- unusually 6 strongly in favor of Fluoxetine, correct? 7 A. That's correct. 8 Q. To the extent that the FDA or 9 Lilly culled it out from the analysis of the rest 10 of the studies that were conducted in the 11 multi-centered study conducted under protocol 12 number 27. Correct? 13 A. That's correct. 14 Q. What was the difference 15 between the Cohn study and the other studies as 16 far as, you know, how much more in favor of 17 Fluoxetine was the Cohn study as opposed to the 18 other studies? 19 MR. MYERS: Wait a minute, when you 20 say the other studies you mean the other centers 21 in that study? 22 MS. ZETTLER: The other studies 23 conducted under protocol 27. 24 MR. MYERS: It also -- the way you Page 466 1 phrased the question it could mean any other 2 study, until you corrected yourself. 3 MS. ZETTLER: I think the Doctor knew 4 what I meant. 5 MR. MYERS: I understand that, but it 6 may not say that in black and white when it's 7 typed up. 8 A. If I could help perhaps, I 9 would consider it one study, protocol 27 was one 10 study. 11 Q. The trials? 12 A. And there were multiple sites, 13 at least that's the terminology. 14 Q. The trials conducted -- the 15 multi-center study trials conducted under 16 protocol 27? 17 A. Single trial or single study, 18 multiple sites. 19 Q. There were six studies 20 conducted under protocol 27 that were considered 21 a multi-center study, correct? 22 A. That's correct. 23 Q. Doctor Cohn's study was far 24 more in favor -- the results were far more in Page 467 1 favor of Fluoxetine than the other five, correct? 2 A. Yes. As I recall, that is 3 correct. 4 Q. What was the difference, I 5 mean how much more in favor of Fluoxetine was 6 Doctor Cohn's study? 7 A. I don't recall precisely and 8 although I could be incorrect, my recollection is 9 that it was -- that the difference was seen 10 primarily in what we call a responder rate 11 analysis. Where you take an arbitrary percentage 12 improvement in the total Hamilton score as 13 opposed to actual Hamilton scores at end point 14 and require patients to have been on drug for a 15 certain length of time before you -- before you 16 allow patients into your responder analysis, and 17 then calculate the percent of responders versus 18 the percent of non-responders. So let's say that 19 you're treating with drug-X and you start with a 20 hundred patients and after four weeks -- at weeks 21 four, five or six, you have seventy patients 22 left. Of that seventy percent of patients, do 23 you calculate a percent response, that being the 24 patients who had a Hamilton score of fifty -- Page 468 1 decrease of fifty percent or less. 2 Q. Doctor, let me -- I think -- 3 MR. MYERS: Wait a minute. 4 MS. ZETTLER: Let me withdraw my 5 question because he obviously didn't understand 6 it the way I asked it and I think it was a bad 7 question. 8 Q. Do you know, for instance, 9 whether fifty percent of the people on Doctor 10 Cohn's study got better on Fluoxetine as opposed 11 to twenty percent of the people on, say, Doctor 12 Dunner's study getting better, do you know what 13 the percentage difference is -- the actual 14 percentage difference was compared to placebo or 15 Imipramine between Doctor Cohn's study and the 16 other studies? 17 A. No, I don't. 18 Q. For whatever reason that 19 Doctor Cohn's study was -- came out more positive 20 in favor of Fluoxetine, I need to understand -- I 21 need you to explain to me why it is that you felt 22 that this same thing couldn't have biased the 23 safety aspects of the drug. 24 A. By safety, I am -- would be Page 469 1 thinking of the reporting of adverse events while 2 patients are taking drug. In fact, you had 3 patients -- from this it would appear to me that 4 it's likely that Doctor Cohn's patients remained 5 on Fluoxetine -- more patients remained on 6 Fluoxetine longer than on Imipramine or placebo. 7 I am believing that Doctor Cohn's reporting of 8 adverse events was correct and accurate. Again, 9 I don't read anything into this to suggest that 10 he was biased in reporting what he observed. 11 That there was this artifact of the -- that there 12 was this aspect of the design of the protocol 13 that may have led patients to discontinue who 14 were on placebo or Imipramine earlier than 15 patients who were on Fluoxetine, allowing 16 Fluoxetine patients to have a longer time to show 17 improvement. That would result in the efficacy 18 difference. That's how I read this as a 19 description of the bias. 20 Q. This says here, does it not, 21 that patients who were not doing well could be 22 dropped at the end of second week and be switched 23 to Fluoxetine after breaking the blind and 24 determining if the patient was on Imipramine or Page 470 1 placebo, correct? 2 A. That's correct. 3 Q. That implies that the doctor 4 could drop the patients, not necessarily that the 5 patient dropped out because of adverse events, 6 correct? 7 A. That's correct. But then they 8 would be on a -- the longer patients are on a 9 particular treatment, the longer percentage -- 10 the longer amount of time they have to experience 11 or to report an adverse event that would then be 12 reported by an investigator. 13 Q. So what's to say that Doctor 14 Cohn wasn't dropping people from the placebo or 15 Imipramine phase of the trial and stacking them 16 in the Fluoxetine part of the trial to jack the 17 numbers around? 18 A. Oh -- 19 MR. MYERS: Hold on, okay. I object 20 to the form to the extent you're assuming that 21 that happened. 22 MS. ZETTLER: I said what is to 23 prevent them, I didn't say it did. 24 A. From your question, I'm Page 471 1 concerned that you're not understanding the 2 conduct of the study. Once they were dropped 3 from double-blind, they went on to open label 4 Fluoxetine. That's an entirely separate 5 different arm. That's not the Fluoxetine arm 6 that's compared to placebo or Imipramine. 7 Q. It doesn't say that here, does 8 it? 9 A. I could graft it, I mean if -- 10 MR. MYERS: She wants to know if it 11 says it in that memo. 12 A. No, it does not. It does not 13 explain it in this memo, but these individuals 14 were, I think, familiar with research design. 15 Q. In fact it differentiates 16 between two different things here. It says in 17 the main efficacy trials patients who were not 18 doing well could be dropped at the end of the 19 second week and switched to Fluoxetine after 20 breaking the blind and determining if the patient 21 was on Imipramine or placebo, correct? 22 A. That was -- 23 Q. Correct, yes or no? 24 A. Yes, that's correct. Page 472 1 Q. The second was the blind could 2 also be broken at trial completion at week six in 3 patients doing well and could be continued on 4 Fluoxetine or Imipramine if these were the drugs 5 they were receiving, correct? 6 MR. MYERS: You want to know if that's 7 true or if that's what it says? 8 MS. ZETTLER: That's what it says. 9 MR. MYERS: Okay. 10 MS. ZETTLER: So you're saying -- but 11 you're saying it's not true? 12 MR. MYERS: No. I'm just asking what 13 your question is, in other words, is the memo a 14 correct recitation of what happened in the study. 15 Q. Then it says this led to a 16 situation where an end point analysis could 17 compare patients' scores after two weeks on 18 placebo with Fluoxetine scores after six weeks of 19 treatment leaving no time for spontaneous 20 improvement in the placebo group and leading to a 21 biased comparison, correct? 22 A. That's correct. 23 Q. So you're saying that this is 24 not two different things here, that this is the Page 473 1 same thing where it talks about patients who were 2 dropped at the end of second week and being 3 switched to Fluoxetine, that the compassionate 4 use is part of protocol? 5 A. It was an open label 6 cross-over. 7 Q. And so both things they say 8 here are both open labelled cross-over parts, 9 portions of the protocol? 10 A. That's correct. Patients 11 after two weeks who were not doing well, the 12 blind could be broken. 13 Q. Two weeks of not doing well 14 according to who, the patient or the 15 investigator? 16 A. According to the investigator, 17 with the patients -- the investigator would 18 ultimately make that decision, but clearly in 19 dialoguing with the patient. 20 Q. The patient would know they 21 were being switched to another drug? 22 A. They would know that they were 23 being placed on open label medication. 24 Q. Would they know which drug Page 474 1 they were being switched to? 2 A. I believe they would. 3 Q. I guess I'm still confused as 4 to why you felt confident in using Doctor Cohn's 5 study in a safety analysis when Lilly didn't feel 6 confident in using it in an efficacy analysis 7 because it was so obviously in favor of 8 Fluoxetine. 9 A. We had absolutely no reason to 10 doubt his safety data whatsoever. In fact, given 11 a differential drop-out rate, the conclusion that 12 you might draw is it's potentially biased against 13 Fluoxetine in terms of reporting adverse events, 14 because more patients remained on Fluoxetine 15 longer than Imipramine as an example, so there 16 was less time for Imipramine or placebo patients 17 to experience adverse events. 18 Q. And that would be biased in 19 favor of Fluoxetine? 20 A. That would be biased against 21 Fluoxetine, excuse me, if I said that. 22 Q. Let's focus on the Ham-D 3 23 rating again. Even though Doctor Cohn's ratings 24 were generally in favor of -- more in favor of Page 475 1 Fluoxetine on the Ham-D, generally. You still 2 felt that the Ham-D 3 was not being affected by 3 that general trend to rate Fluoxetine patients 4 better on the Ham-D? 5 A. I don't recall specifically 6 thinking of the issue at the time the report was 7 developed. 8 Q. Did you discuss that at any 9 time with any of your colleagues whether or not 10 Cohn's study could be biased in favor of 11 Fluoxetine on the Ham-D 3 rating scale or 12 question as well as the rest of the rating scale? 13 A. I don't recall that. 14 Q. Anybody attempt suicide on 15 Doctor Cohn's Protocol 27 trial? 16 A. I don't know. 17 Q. Doctor Cohn's protocol 27 18 trial was, in fact, published as being 19 demonstrative of efficacy of Fluoxetine even 20 though it was not used in the efficacy analysis 21 by the FDA, correct? 22 A. It was published, it was also 23 submitted to the FDA separately. 24 Q. It was not considered by the Page 476 1 FDA in efficacy, though, was it? 2 A. I don't know what 3 consideration they gave to it since it was split 4 out. It was not considered as part of the two 5 pivotal trials. 6 Q. Because of its bias or the 7 results' bias in favor of Fluoxetine? 8 A. Again, I am -- I know that it 9 was cut out, I believe that it was cut out by 10 Lilly, I do not believe it was considered 11 pivotal. I could speculate that that was the 12 case, but I don't know definitively why the FDA 13 made the decisions they made. 14 Q. Any other studies that Doctor 15 Cohn did for Lilly on Fluoxetine where the 16 results were too strongly in favor of Fluoxetine 17 compared to other studies? 18 A. Again, we're talking 19 multi-site within the same -- I'm not aware of 20 any. 21 Q. How about the bipolar study, 22 were the results of his study much better on 23 Fluoxetine than they were for any other 24 comparator that was used? Page 477 1 A. I don't recall the specific 2 results of that study. 3 Q. How about the geriatric study 4 that he did? 5 A. I don't recall which study 6 that was. 7 Q. Weren't any of the geriatric 8 studies included in your meta-analysis? 9 A. I believe there is a two-site 10 study that I think I can find. Yes, it is number 11 nine. 12 Q. Number nine, okay. And that 13 lists Cohn and Feighner, correct? 14 A. Right. 15 Q. How about that study, how were 16 Doctor Cohn's results compared to Doctor 17 Feighner's? 18 A. I have no specific knowledge 19 of what differences existed or did not exist 20 between the two investigators. 21 Q. Were the results of these 22 studies conducted under protocol 27 as used in 23 your analysis, your meta-analysis, were those 24 results pooled and considered one or were they Page 478 1 looked at individually? 2 A. They were considered as a 3 single protocol. 4 Q. Right. But what about the 5 individual trials done under that protocol, were 6 they analyzed as one group of patients or were 7 they analyzed individually? 8 A. They were analyzed as one 9 group of patients. 10 Q. Is that the same with these 11 other multiple trial? 12 A. Multi-center. 13 Q. Multi-center studies. Like 14 for instance number 9, Doctor Cohn's and Doctor 15 Feighner? 16 A. Yes. 17 (PLAINTIFFS' EXHIBIT NO. 18 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 A. I have looked at this. 21 Q. Do you recognize Exhibit 18? 22 A. I do not recognize it in that 23 I cannot recall having seen it previously. I see 24 reference on the second page to safety update. Page 479 1 Q. Under U.S. IND pharmacology? 2 A. That's correct. 3 Q. Isn't that a reference of 4 where information -- or where this information 5 was gleaned from, the safety update, page 48 to 6 51? 7 A. I'm not certain what the 8 document is. I think it probably is something of 9 a table of contents of a document referred to as 10 a safety update. 11 Q. Why do you say that? 12 A. Because it listed study 13 numbers and then it listed safety update pages 14 and then I'm not sure -- and then it listed the 15 number of Fluoxetine patients. So it must be 16 referring to where patients were treated and how 17 many were treated and where they can be found in 18 the safety update. 19 Q. Okay. First page says based 20 on the data available October 15th, 1986, 21 correct? 22 A. That's correct. 23 Q. Would that indicate to you 24 that the studies listed in here were at least the Page 480 1 status of the studies as of October 15th, 1986? 2 A. That's correct. 3 Q. Okay. Let's look at the -- 4 second page of the exhibit lists U.S. IND 5 pharmacology studies, correct? 6 A. That's correct. 7 Q. And then it lists U.S. IND 8 open label studies, correct? 9 A. That's correct. 10 Q. And then the next page lists 11 IND placebo controlled studies, does it not? 12 A. That's correct. 13 Q. And that continues on to the 14 next page? 15 A. That's correct. 16 Q. Under that, it says U.S. IND 17 comparator controlled studies, correct? 18 A. That's correct. 19 Q. And after that, it says U.S. 20 IND other controlled, correct? 21 A. That's correct. 22 Q. What are other controlled 23 studies? 24 A. From this information I can't Page 481 1 tell what these studies are. 2 Q. What other controls would be 3 used in studies besides placebo comparator 4 antidepressant? 5 A. Well, let me -- I believe this 6 looks across, and I could be wrong, looks across 7 all indications. 8 Q. So the Rickels, Bremner, 9 Grosser, Abuzzahab studies listed under other 10 controlled could be other indications? 11 A. Given this number of patients 12 that's being referred to, again, eight thousand 13 five hundred and twenty-six, and four thousand 14 five hundred and fifty-five, it doesn't indicate 15 to me on this whether they're talking about just 16 depression or other indications. I would 17 strongly believe that it's a good possibility 18 that we're also talking about other indications 19 here. 20 Q. Okay. I thought you weren't 21 done with your answer. Going back to page two or 22 page three of the exhibit -- going back to page 23 two, were all of these studies listed included in 24 your meta-analysis? Page 482 1 A. The U.S. IND placebo 2 controlled trials. Given that I don't know 3 specifically what these studies are from this 4 sheet, but to the best of my knowledge, all U.S. 5 IND placebo controlled trials for depression were 6 contained in this meta-analysis. 7 Q. Except for the bi-polar 8 disorder study? 9 A. I made reference to 10 depression. 11 Q. But that's not a pure 12 depression study. It's a bi-polar disorder 13 study, correct, with an element of depression in 14 it? 15 A. Patients had to meet full 16 criteria for major depression at the time they 17 entered the study. 18 Q. So they couldn't be in a manic 19 phase, they had to be in a depressive phase. 20 A. Yes. They had to be in a 21 depressive phase. 22 Q. Is it easier to predict when 23 somebody is going to go in a manic phase? 24 A. If there is good knowledge of Page 483 1 longitudinal course, there may be some capacity 2 to predict it. For the most part it does not 3 make radical shifts in terms of a phase, but 4 again, that's rough, that's not absolute. 5 Q. There is a difference between 6 a diagnosis of major depressive disorder and 7 bi-polar depression, correct? 8 A. That's correct. 9 Q. They're two very different 10 patients in a lot of ways, are they not? 11 A. In many respects, if you look 12 across time, absolutely. 13 Q. Do you believe that people 14 suffering from OCD have a component of depression 15 to their illness or can they have a component of 16 depression to their illness? 17 A. It can be a co-morbid 18 condition. It is seen co-morbidly associated 19 with obsessive-compulsive disorder more 20 frequently in the general population, I believe. 21 Q. How about bulimia? 22 A. I'm less certain about the 23 association with bulimia than OCD, but that could 24 well be the case. Page 484 1 Q. To your knowledge, were any 2 trials done on OCD patients who had to meet the 3 criteria for depressive illness at the time of 4 entry into the study, such as the bi-polar 5 disorder study? 6 A. So that the patients had to 7 have simultaneously meet full criteria for both? 8 Q. Right. 9 A. I'm not aware of such study. 10 Q. How about bulimia? 11 A. Where they were absolutely 12 required to have both conditions, no. 13 Q. Is the bi-polar study listed 14 on this exhibit, to your knowledge? 15 MR. MYERS: Will looking at the paper 16 be of any help to you, Doctor? 17 THE WITNESS: No, because I don't know 18 the IND protocol number for the bi-polar study. 19 Q. Okay. If you count up the 20 studies using your methodology in the paper of 21 including, for instance, all the trials that were 22 done under protocol number 27 as one study. 23 There is only fifteen that are listed in this 24 first two sections entitled placebo controlled or Page 485 1 comparator controlled safety. Do you see that? 2 A. Yes. I haven't added them up, 3 but -- 4 Q. Given that one of the other 5 studies that was added was the bi-polar study, 6 was the sixteenth study or the seventeenth, would 7 have wound up being the seventeenth study, would 8 that have been another depression study, 9 controlled study, as far as you know? 10 A. Everything that's in this 11 particular paper was a depression study. 12 Q. Okay. Is it fair to say that 13 other double-blind controlled studies on 14 depression and Fluoxetine were completed prior to 15 December, 1989 that either are on this list as 16 ongoing or were started sometime after this list 17 was created? 18 MR. MYERS: I object to the form and 19 ask, when you say completed how far along do you 20 mean? 21 MS. ZETTLER: Where they could be used 22 in the analysis. 23 A. We took every study that had 24 been completed and unblinded and was available on Page 486 1 the computer at the time we began working on the 2 data base, that was completed in depression. 3 There is actually one exception to that. There 4 was a study initiated, I believe in Georgia, 5 which was terminated, never analyzed from an 6 efficacy perspective, because as I understand it 7 at the time, this was long before I arrived, 8 there were serious questions about, in this case, 9 the validity of the efficacy data, the actual 10 ratings. This study was not included. 11 Q. It was not included? 12 A. This was not included, that's 13 correct. 14 Q. Is this the -- it was not 15 included? 16 A. It was not included. 17 MR. SMITH: This is a study that was 18 done, patients were enrolled and yet it was -- 19 the study was dropped? 20 THE WITNESS: That's my understanding. 21 Q. (BY MS. ZETTLER) At what 22 point was it dropped, before the last patient was 23 treated? 24 A. My understanding was that Page 487 1 there had been a planned number of patients, but 2 the study was -- the site was shut down prior to 3 the enrollment of that number of patients. I 4 forget the specific number of patients who had 5 been enrolled. 6 Q. And that was because there was 7 a problem or a concern about the validity of the 8 efficacy data that was being generated by the 9 study? 10 A. That's my recollection of the 11 reason that the study was terminated and shut 12 down. 13 Q. What problems with the 14 efficacy data? 15 A. As I recall -- and again, I'm 16 not even certain that the -- I don't recall 17 speaking specifically with the CRA and I believe 18 that the physician who had monitored the study 19 had long since gone. There were questions about 20 whether the investigator had reliably recorded 21 data, particularly efficacy data. 22 Q. How would such questions arise 23 during the course of a study? 24 A. Hypothetically? Page 488 1 Q. No, in this situation. How 2 was it that Lilly became concerned that the 3 investigator was not recording efficacy data the 4 right way? 5 A. I have no knowledge of that. 6 MR. SMITH: How did you know about it? 7 THE WITNESS: How did I know about it? 8 MR. SMITH: Yes. 9 THE WITNESS: There was -- when we 10 reviewed the data base, sat down and looked at 11 all the studies and a computer listing of how 12 those studies were organized, I wanted to have 13 explained to me what each of these -- in the 14 computer data base it's a series of letters and 15 then a brief title -- means. And this had a 16 series of letters, I don't recall what the 17 letters were, and the title was something like -- 18 the title was No Code Break, as I recall. 19 Q. (BY MS. ZETTLER) Was the name 20 of the study? 21 A. Well, on the computer listing 22 that printed out for all the studies that existed 23 in the data base -- 24 Q. Uh-huh. Page 489 1 A. -- that was the -- that was 2 the reference, that was the label. That was a 3 very unusual study name, very clearly 4 interesting, I had to know what that study was. 5 Q. Did you find out why they 6 called it No Code Break? 7 A. Because it had basically never 8 been analyzed, at least for efficacy. 9 Q. How did they know there was a 10 problem with the recording of efficacy data? 11 A. The case report forms had been 12 collected, okay. It had been placed on the 13 computer. Again, I have no knowledge of how it 14 was determined or with what probability it was 15 determined that there were problems with the 16 data. My understanding was that there were -- 17 there had been, put this in the past tense, there 18 had been sufficient concerns not to analyze it 19 and therefore it received the distinction No Code 20 Break. 21 MR. MYERS: Paul, wait a minute. You 22 all don't go back and forth, really, I'm serious. 23 I'll give you a little bit of leeway, but -- 24 MS. ZETTLER: What would you like me Page 490 1 to ask him, Paul? 2 Q. Do you remember what protocol 3 the study was conducted under? 4 A. No. As I said, I don't know 5 the protocol number or the code nor the 6 investigator's number. The thing that I 7 remember, I hope correctly, is this name No Code 8 Break. 9 Q. Do you recall what the trial 10 was studying, was it Fluoxetine compared to 11 placebo or another comparator or both? 12 A. I believe, it was Fluoxetine 13 versus placebo. 14 Q. Okay. How many patients? 15 A. It was not an -- it was not a 16 three arm study. 17 Q. Okay. It was a two arm study? 18 A. And it could have been and a 19 comparator, I think it was placebo. 20 Q. You're pretty sure it was not 21 a three arm study? 22 A. I'm virtually certain it was 23 not a three arm study. 24 Q. How many patients? Page 491 1 A. I don't recall the specific 2 number of patients that were entered. It was a 3 small number, meaning less than hundreds, I 4 believe, a few tens. 5 Q. Like maybe thirty? 6 A. I'm being approximate. 7 Q. Any other Prozac depression 8 controlled trials that were not included in your 9 analysis that you know of? 10 A. Again, we're speaking about 11 major depressive syndrome in the United States? 12 Q. Right. 13 A. There were Trazodone, at least 14 one Trazodone comparison study. 15 Q. Why didn't you include that 16 one? 17 A. That was one -- only one study 18 with a single different comparator that we felt 19 could not be lumped with the tricyclics. So 20 very, very small power. 21 Q. There was only one Trazodone 22 study that was done at that time? 23 A. I believe that was the case. 24 Q. Any other anti-depressant Page 492 1 comparator studies that were not used that you 2 know of? 3 A. In the U.S. we used all 4 available tricyclic studies. I don't believe we 5 had any other comparators except Trazodone. 6 Q. What is Trazodone's brand 7 name? 8 A. Desyrel, it's generic now. 9 Q. Does that have a sedative 10 effect? 11 A. Yes, it does. 12 Q. You didn't -- did you in your 13 paper do a breakdown of the rates between 14 Fluoxetine in each individual comparator, besides 15 placebo, or did you lump all the tricyclics 16 together? 17 A. We placed all the tricyclics 18 together. 19 Q. Why? 20 A. The acute bio-chemical 21 pharmacology of these is relatively comparable in 22 that they are primarily norepinephrine uptake 23 inhibitors. They're secondarily seratonin uptake 24 inhibitors, but weak. The majority of the Page 493 1 comparators -- well, let's see, I believe at the 2 time this was done, in fact, they were all what 3 we call tertiary amine tricyclics. This includes 4 Imiprimine, which was the majority, Amitryptiline 5 and Doxepin. These are -- there are other 6 tricyclics as well. These three tertiary amine 7 compounds are even more comparable in their 8 activity than if you spread to the entire, both 9 tertiary and secondary amine tricyclics. 10 Q. How many other journals did 11 you submit that paper to before it was published 12 in the BMJ? 13 A. One. 14 Q. New England Journal of 15 Medicine? 16 A. That's correct. 17 Q. How many times did you submit 18 it to the New England Journal of Medicine? 19 A. If I recall correctly, only 20 once. 21 Q. How many revisions did you do 22 on it? 23 A. None for the New England 24 Journal. Page 494 1 Q. Why not? 2 A. The rejection letter was 3 rather interesting to me. It was the most 4 positive rejection letter that I've ever received 5 regarding content. The thrust was this is a 6 subject -- we received many fine papers, et 7 cetera, et cetera, we feel that -- the editorial 8 board feels that this would be a subject not of -- 9 I'm paraphrasing -- interest to our readership or 10 to specific, a topic to our readership. 11 Q. Sounds like a canned rejection 12 letter, doesn't it? 13 A. Actually I had a somewhat 14 different characterization of it. 15 Q. How many rejection letters 16 have you gotten on publications or manuscripts 17 that you have submitted for publication? 18 A. Absolute flat rejections as 19 opposed to please revise this, I could be 20 incorrect here but I believe one. 21 Q. One other besides the New 22 England Journal of Medicine rejection? 23 A. That's correct. 24 Q. So compared to the New England Page 495 1 Journal of Medicine rejection, the other one must 2 have been awful, was it? 3 A. It was critical of content. 4 Q. What article -- was it a 5 Fluoxetine article? 6 A. Yes, it was. It was -- in a 7 certain way it was critical of content. It was a 8 write-up of the three Amitryptiline, Fluoxetine 9 sites as a single report. It was rejected by the 10 Journal of Clinical Psychiatry. One of the 11 reviewers referred to this as, I believe, old 12 wine in a new bottle. 13 Q. They -- 14 A. It was not terribly 15 technically -- they were not technically 16 critical, but not -- 17 Q. They had seen it before, they 18 had seen it all before kind of thing? 19 A. That was their impression. 20 Q. Did -- was this a republishing 21 of data that had been -- in other words, were the 22 three studies pooled and at another time they had 23 been reported separately? 24 A. They had been reported Page 496 1 separately previously, that's correct. 2 Q. In that journal? 3 A. Actually, I think one of them 4 had been. 5 Q. Okay. What -- other than the 6 fact that they had seen it all before, did they 7 have any other criticism of your pooling the 8 Amitryptiline study data together to analyze? 9 A. No. As I recall the rejection 10 letter was probably about a page or page slightly 11 plus long. That's the one comment I remember. 12 Q. Okay. So since you only had 13 one other rejection letter, how is it -- 14 A. That one was -- go ahead, I'm 15 sorry. 16 Q. How is it that you can say 17 that the New England Journal of Medicine's 18 rejection letter was the most positive rejection 19 letter you ever received? 20 A. That -- first of all, the New 21 England Journal was actually received previously, 22 as opposed to after that. 23 Q. Okay. 24 A. I was making that statement in Page 497 1 a positive -- in an absolute sense of I thought 2 there were nice things sort of said about 3 actually the data, but it's not for us. I mean 4 it would be nice to get a -- it's more helpful to 5 get a -- I think a rejection that says do 6 something differently. 7 Q. Did you -- like you did with 8 the BMJ? They initially said do something 9 differently or we're not going to publish it like 10 this, correct? 11 A. As I recall, we received about 12 eight to ten pages of commentary and suggestions. 13 Q. And they basically let you 14 know that if you didn't make the changes, that 15 they -- initial changes that they suggested or at 16 least make some attempt at satisfying their 17 concerns about those changes, that they weren't 18 going to publish the paper? 19 A. That's correct. 20 Q. How come you went to the BMJ 21 instead of going to other publications here in 22 the United States? 23 A. There were -- we wanted to get 24 this into a, if at all possible, a prestigious Page 498 1 general, as opposed to specialty journal. That 2 was very important to us. 3 MR. SMITH: Why. 4 THE WITNESS: That would receive -- 5 Q. (BY MS. ZETTLER) You can 6 answer it, Doctor. 7 MR. MYERS: Go ahead. 8 A. We felt that it would 9 therefore receive the widest potential 10 readership. 11 Q. Why didn't you go to JAMA 12 then? 13 A. There was concern that the 14 American journals might be -- not looked 15 favorably, particularly JAMA on the material 16 submitted by the pharmaceutical industry. It was 17 then suggested to us by Doctor Keohane in the UK 18 that we consider the BMJ. 19 Q. Why was it thought that JAMA 20 would not look at an article by the 21 pharmaceutical industry favorably? 22 A. It was our concern that they 23 might have concerns about showing favoritism to 24 the industry, or in some sense siding with the Page 499 1 industry. Our interpretation of the rejection by 2 the New England Journal was that that might be an 3 issue for them. 4 Q. Let me get this straight. 5 Your interpretation of this glowingly positive 6 rejection letter that you got from the New 7 England Journal of Medicine was that another 8 journal in the United States, including the New 9 England Journal of Medicine, potentially would 10 have not looked at your paper in a positive way? 11 A. That's correct. 12 Q. Have -- before you started 13 with Lilly, did you ever publish any papers? 14 A. I had submitted one for 15 publication. I believe it was submitted -- it 16 grew out of my research activities as a senior 17 resident, so the work had been done prior to 18 coming to Lilly. I'm not sure if the first draft 19 of that paper was submitted before I came to work 20 for Lilly or not. 21 Q. To your knowledge, has anybody 22 submitted, from Lilly, submitted any papers to 23 the national or to the New England Journal of 24 Medicine or to JAMA on any other issue where it's Page 500 1 been accepted? 2 MR. MYERS: Fluoxetine? 3 MS. ZETTLER: Any other issue where 4 it's been accepted and published, any other drug, 5 anything else, any other papers that have been 6 written by Lilly. 7 A. Oh, written by Lilly 8 submitted? 9 Q. Submitted to the New England 10 Journal of Medicine where it's actually been 11 published? 12 A. I'm not aware of the New 13 England Journal publishing any primary Lilly 14 papers, nor am I aware of Lilly submitting a 15 primary Lilly authored paper to the New England 16 Journal. I could be incorrect about that. 17 Q. How about the Journal of the 18 American Medical Association? 19 A. Similar with the -- with JAMA, 20 Journal of the American Medical Association, I'm 21 unaware of any articles being published by them 22 that have been submitted by primary Lilly authors 23 and I'm unaware of Lilly authors submitting 24 those, certainly in recent history. Page 501 1 Q. Who made the decision to 2 submit the meta-analysis article to the New 3 England Journal of Medicine? 4 A. I'm not certain who made that 5 final decision. 6 Q. Who was involved in the 7 decision making? 8 A. I would say a number of 9 people. 10 Q. Give me some names, Doctor. 11 A. Doctor Weinstein. 12 Q. Okay. 13 A. Anybody else? 14 Q. Probably Doctor Thompson, 15 myself, Doctor Masica, Doctor Zerbe. 16 Q. Did you have a meeting on the 17 issue? 18 A. I can't recall a specific 19 meeting. One or more meetings may certainly have 20 taken place. 21 Q. Was there a specific decision 22 made between submitting the article initially to 23 the New England Journal of Medicine and JAMA? 24 A. I'm -- I don't recall to what Page 502 1 extent JAMA was ever considered. 2 Q. Was there anybody in this 3 group that was opposed to submitting the paper 4 initially to New England Journal of Medicine? 5 A. I don't think there was anyone 6 opposed. 7 Q. Did anyone have any 8 reservations? 9 A. I believe that I probably 10 expressed concerns about whether or not it would 11 be published by that journal. I was certainly 12 hopeful that it would. I didn't know whether it 13 would or not. 14 Q. Anybody else that would have 15 had reservations or expressed reservations that 16 you recall? 17 A. No. Everyone was, I believe, 18 in recalling, I believe pretty enthusiastic. 19 Q. Why were you concerned or have 20 reservations about whether or not it would 21 actually be published in the New England Journal 22 of Medicine? 23 A. There are occasions when I'm, 24 I think, less than optimistic about work of mine Page 503 1 going into such a prestigious journal. 2 Q. Why? 3 A. I don't have a particular 4 reason, that's just an outlook. 5 Q. Why do you think you were 6 chosen to be the lead author on this article? 7 A. I had done a good deal of the 8 background clinical work and had actively 9 participated in the -- very actively participated 10 in the coordination of the project. 11 Q. Was Doctor Wheadon still with 12 Lilly during the time when the -- after 1990, 13 when Doctor Teicher's article came out up until 14 the time that this article was published in the 15 BMJ? 16 A. I believe he was. 17 Q. How about Doctor Wernicke? 18 A. Doctor Wernicke was no longer 19 present. 20 Q. When did he leave Lilly? 21 A. I don't recall precisely. 22 Q. Was it before or after 23 Teicher's article came out? 24 A. Doctor Wernicke left before. Page 504 1 Q. How about Doctor Weinstein, 2 was he -- he was still there, wasn't he? 3 A. Yes, he's still with Lilly. 4 Q. Doctor Weinstein was involved 5 with the German issue, wasn't he? 6 A. He might well have been by 7 virtue of his position with International. 8 Q. Doctor Weinstein, Doctor 9 Thompson, Doctor Masica and Doctor Zerbe had all 10 been with Lilly longer than you, correct? 11 A. Zerbe, Doctor Weinstein -- 12 yes. 13 Q. What did you do between the 14 time -- with your time between graduating from 15 undergrad and going to medical school? 16 A. I worked for two years in 17 computer science. The first year I continued my 18 work basically as a research assistant for my 19 senior professor in an artificial intelligence 20 project, that was -- so I was funded on his 21 grant, basically conducting research, doing 22 artificial intelligence program for him. 23 Q. Okay. 24 A. The next year, I was in the Page 505 1 medical school application process. He left New 2 Haven and transferred to Pittsburg. I did not 3 want to make that move with him since I was 4 completing the application process, felt that I 5 would be in medical school the next year, and 6 took a job in the department of neurology for the -- 7 paid by them. I was actually working out at an 8 electrophysiology laboratory out at the V.A. 9 Hospital in West Haven, Connecticut setting up a 10 data base management system for evoke potential 11 data. 12 Q. Did you have any patient 13 responsibilities during that period of time? 14 A. No. I worked with numbers and 15 developed -- they did the majority of their work 16 on primates as opposed to humans, although they 17 did some on humans, so I had a connection with 18 some human data, but not actually subjects, it 19 was a research project. 20 Q. How about between medical 21 school and your residency and internship, what 22 did you do then? 23 A. I went directly to my 24 internship, I went to New Haven. My wife to be Page 506 1 also went to New Haven, she took a one year 2 internship in internal medicine at Yale. 3 Q. How many people graduated from 4 your medical school class? 5 A. I think about ninety-four. 6 Q. Where were you ranked in that? 7 A. I think I was four or six. 8 MS. ZETTLER: I think this is a good 9 place to stop. 10 MR. SMITH: Let me ask a question. 11 MR. MYERS: Go ahead. 12 REDIRECT EXAMINATION 13 BY MR. SMITH: 14 Q. Where is the APA convention? 15 A. Philadelphia. 16 Q. Philadelphia. And is anyone 17 from Lilly going to present any data, papers, 18 abstracts or posters concerning Prozac and 19 suicidality or aggressive violent behavior? 20 MR. MYERS: Nancy already asked all 21 that. 22 MS. ZETTLER: Actually he changed it. 23 MR. MYERS: Go ahead, Doctor. 24 A. I'm unaware of anyone from Page 507 1 Lilly presenting anything on that subject. 2 MS. ZETTLER: Are you aware of anybody 3 presenting anything on those subjects? 4 A. I am not aware of anyone -- 5 again, an independent investigator or I'm not on 6 the program committee, so some external 7 individual could be doing so. I don't know that 8 that's the case. 9 MS. ZETTLER: We'll be getting in 10 touch with you through either Larry or Mary soon. 11 (DISCUSSION OFF THE RECORD.) 12 (THE WITNESS WAS EXCUSED.) Page 508 1 COMMONWEALTH OF KENTUCKY ) 2 : ss COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 DR. CHARLES BEASLEY 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 2ND DAY OF 19 JUNE, 1993. 20 MY COMMISSION EXPIRES MARCH 10, 1998. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 509 1 2 E R R A T A S H E E T 3 4 STATE OF ) : SS 5 COUNTY OF ) 6 7 8 I, DR. CHARLES BEASLEY, THE 9 UNDERSIGNED DEPONENT, HAVE THIS DATE READ THE 10 FOREGOING PAGES OF MY DEPOSITION AND WITH THE 11 CHANGES NOTED BELOW, IF ANY, THESE PAGES 12 CONSTITUTE A TRUE AND ACCURATE TRANSCRIPTION OF 13 MY DEPOSITION GIVEN ON THE 17 AND 18 DAY OF MAY, 14 1994, AT THE TIME AND PLACE STATED THEREIN. 15 PAGE NO. LINE NO. CHANGE REASON Page 510 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. CHARLES BEASLEY 10 11 SWORN TO AND SUBSCRIBED BEFORE ME THIS 12 _____ DAY OF __________, 1994. 13 _____________________________ NOTARY PUBLIC, STATE OF 14 INDIANA AT LARGE 15 16 17 18 19 20 21 22 23 24 Page 511 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Page 512 1 DIRECT EXAMINATIONBY MR. SMITH:...................12 2 FURTHER DIRECT EXAMINATIONBY MR. SMITH:..........273 3 REDIRECT EXAMINATION BY MR. SMITH: ..............507 4 CROSS EXAMINATION................................376 5 (PLAINTIFFS' EXHIBIT NO. 15......................412 6 PLAINTIFFS' EXHIBIT NO. 1........................143 7 PLAINTIFFS' EXHIBIT NO. 2........................167 8 PLAINTIFFS' EXHIBIT NO. 3........................200 9 PLAINTIFFS' EXHIBIT NO. 4........................208 10 PLAINTIFFS' EXHIBIT NO. 5........................212 11 PLAINTIFFS' EXHIBIT NO. 6........................217 12 (PLAINTIFFS' EXHIBIT NO. 7.......................280 13 (PLAINTIFFS' EXHIBIT NO. 8.......................298 14 (PLAINTIFFS' EXHIBITS NO. 9 AND 10...317 15 (PLAINTIFFS' EXHIBIT NO. 11......................354 16 (PLAINTIFFS' EXHIBIT NO. 12......................388 17 (PLAINTIFFS' EXHIBIT NO. 13......................394 18 (PLAINTIFFS' EXHIBIT NO. 14......................411 19 (PLAINTIFFS' EXHIBIT NO. 16......................441 20 (PLAINTIFFS' EXHIBIT NO. 17......................457 21 (PLAINTIFFS' EXHIBIT NO. 18......................479 Page 513