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. DAVID WHEADON 11 DATE: JUNE 9 AND 10, 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 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS 3 COUNTY DEPARTMENT - LAW DIVISION 4 RENATO DI SILVESTRO, Individually ) and as Special Administrator of ) 5 the Estate of JOHN DI SILVESTRO, ) Deceased, ) 6 ) Plaintiff, ) 7 ) v. ) No. 91 L 7881 8 ) ROBERT L. NELSON, et al., ) 9 ) Defendants, ) 10 ) GEORGE MELNICK, M.D. and PETER ) 11 FINK, M.D. ) ) 12 Respondents in Discovery.) 13 * * * * * * * * * * Page 4 1 IN THE CIRCUIT COURT OF THE SIXTH JUDICIAL CIRCUIT CHAMPAIGN COUNTY, ILLINOIS 2 LINDA GARDNER, Individually and ) 3 as Special Administrator of ) the Estate of SHANE GARDNER, ) 4 deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91 L 1066 ) 7 ELI LILLY AND COMPANY, a foreign ) corporation, ) 8 ) Defendant. ) 9 10 * * * * * * * * * * Page 5 1 SUPERIOR COURT OF THE STATE OF CALIFORNIA 2 FOR THE COUNTY OF LOS ANGELES 3 DR. MARIUS SAINES, etc., et al., ) Case No: 4 ) SC 008331 Plaintiffs, ) 5 ) vs. ) 6 ) ELI LILLY & COMPANY, a corporation; ) 7 DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1- ) 8 100, inclusive, ) ) 9 Defendants. ) ____________________________________) 10 11 * * * * * * * * * * 12 NO. 93-8792-D 13 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF 14 INDIVIDUALLY AND AS SURVIVORS ) AND STATUTORY BENEFICIARIES ) 15 OF MAY YUN KUNG, DECEASED ) ) 16 VS. ) DALLAS COUNTY ) T E X A S 17 ELI LILLY AND COMPANY, DISTA ) PRODUCTS COMPANY, AND MONIQUE ) 18 KUNKLE, PH.D. ) Page 6 1 * * * * * * * * * * 2 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS 3 CIVIL COURT DEPARTMENT 4 EUGENE HUSLIG, AS ADMINISTRATOR ) 5 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 6 HUSLIG, DESCEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 7 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 8 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 9 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 10 ) 94 C 192 PLAINTIFFS, ) 11 ) VS. ) 12 ) COURT NO. 7 MARY L. BILLINGSLEY, EXECUTOR OF ) CHAPTER 60 13 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 14 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 15 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 16 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 17 ) DEFENDANTS. ) Page 7 1 * * * * * * * * * * 2 3 CAUSE NO. 93-04911-A 4 LINDA JILL WELCH, CARLINDA 5 WELCH REX, CONNAN ROSS WELCH AND CHAD MICHAEL WELCH, 6 INDIVIDUALLY AND AS SURVIVORS AND STATUTORY BENEFICIARIES 7 OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 8 V. 9 ELI LILLY AND COMPANY, DISTA PRODUCTS COMPANY, NOE NEAVES, 10 M.D., AND MINITH-MEIER CLINIC, P.A. DEFENDANTS Page 8 1 THE DEPOSITION OF DR. DAVID WHEADON, TAKEN 2 AT THE OFFICE OF BALLARD SPAHR ANDREWS & 3 INGERSOLL, 1735 MARKET STREET, PHILADELPHIS, PA, 4 ON JUNE 9 AND 10, 1992; SAID DEPOSITION TAKEN 5 PURSUANT TO NOTICE IN ACCORDANCE WITH THE RULES 6 OF CIVIL PROCEDURE. 7 * * * * * * * * * * 8 A P P E A R A N C E S 9 10 PAUL SMITH COUNSEL FOR PLAINTIFFS 11 745 CAMPBELL CENTER 2 8115 NORTH CENTRAL EXPRESSWAY 12 DALLAS, TEXAS 75206 13 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 14 1405 W. NORWELL LANE SCHAUMBURG, ILLINOIS 60193 15 JOE FREEMAN 16 LAWRENCE J. MYERS COUNSEL FOR ELI LILLY AND COMPANY 17 FREEMAN & HAWKINS 4000 ONE PEACHTREE CENTER 18 303 PEACHTREE STREET, N.E. ATLANTA, GEORGIA 30308-3243 19 MARY HUFF 20 ELI LILLY AND COMPANY LILLY CORPORATE CENTER 21 INDIANAPOLIS, INDIANA 46285 22 JOHN F. BRENNER COUNSEL FOR ELI LILLY AND COMPANY 23 MCCARTER & ENGLISH FOUR GATEWAY CENTER 24 100 MULBERRY STREET NEWARK, NEW JERSEY 07102-4096 Page 9 1 2 3 KATHERINE L. LAWS 4 COUNSEL FOR DRS. WITSCHY AND KANNEGANTI 5 BAILEY AND WILLIAMS 6 3500 NCNB PLAZA 7 901 MAIN STREET 8 DALLAS, TEXAS 75202-3714 9 10 BEATRICE M. SMITH 11 COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 12 BARTLETT & FRIEND, LLP 13 1301 MCKINNEY, SUITE 2900 14 HOUSTON, TEXAS 77010 15 16 KAREN SEYMOUR 17 COUNSEL FOR DR. BILLINGSLEY 18 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 19 10111 W. 87TH ST. 20 P.O. BOX 12290 21 OVERLAND PARK, KANSAS 66282 22 23 ROBERT L. HARRIS 24 COUNSEL FOR NOE NEAVES, M.D. Page 10 1 SIFFOLD & ANDERSON, LLP 2 6300 NATIONS BANK PLAZA 3 901 MAIN STREET 4 DALLAS, TEXAS 75202 5 6 WILLIAM J. DOWNEY, III 7 COUNSEL FOR PLAINTIFF SAINES 8 KANANACK, MURGATROYD, BAUM & HEDLUND 9 12100 WILSHIRE BOULEVARD, SUITE 650 10 LOS ANGELES, CALIFORNIA 60025 11 12 JAMES D. COLEMAN 13 COUNSEL FOR DEPONENT 14 BALLARD SPAHR ANDREWS & INGERSOLL 15 1735 MARKET STREET, 51ST FLOOR 16 PHILADELPHIA, PENNNSYLVANIA 19103-7599 Page 11 1 I N D E X 2 3 DEPOSITION OF DR. DAVID WHEADON 4 5 6 DIRECT EXAMINATION BY MR. SMITH 14 7 CROSS EXAMINATION BY MS. ZETTLER 356 8 CROSS EXAMINATION BY MR. HARRIS 455 9 10 CERTIFICATE OF SERVICE 459 11 12 ERRATA 460 13 14 EXHIBITS 15 PLAINTIFFS' EXHIBIT NO. 1 101 16 PLAINTIFFS' EXHIBIT NO. 2 121 PLAINTIFFS' EXHIBIT NO. 3 140 17 PLAINTIFFS' EXHIBIT NO. 4 146 PLAINTIFFS' EXHIBIT NO. 5 162 18 PLAINTIFFS' EXHIBIT NO. 6 177 PLAINTIFFS' EXHIBIT NO. 7 185 19 PLAINTIFFS' EXHIBIT NO. 8 204 PLAINTIFFS' EXHIBIT NO. 9 230 20 PLAINTIFFS' EXHIBIT NO. 10 235 PLAINTIFFS' EXHIBIT NO. 11 AND 12 270 21 PLAINTIFFS' EXHIBIT NO. 13 273 PLAINTIFFS' EXHIBIT NO. 14 287 22 PLAINTIFFS' EXHIBIT NO. 15 290 PLAINTIFFS' EXHIBIT NO. 16 301 23 PLAINTIFFS' EXHIBIT NO. 17 304 PLAINTIFFS' EXHIBIT NO. 18 322 24 PLAINTIFFS' EXHIBIT NO. 19 331 PLAINTIFFS' EXHIBIT NO. 20 342 Page 12 1 PLAINTIFFS' EXHIBIT NO. 21 349 2 PLAINTIFFS' EXHIBIT NO. 22 349 PLAINTIFFS' EXHIBIT NO. 23 372 3 PLAINTIFFS' EXHIBIT NO. 24 402 PLAINTIFFS' EXHIBIT NO. 25 421 4 PLAINTIFFS' EXHIBIT NO. 26 430 PLAINTIFFS' EXHIBIT NO. 27 435 5 PLAINTIFFS' EXHIBIT NO. 28 442 PLAINTIFFS' EXHIBIT NO. 29 449 6 Page 13 1 MR. FREEMAN: We'll use the same 2 stipulation that we used in Mister Wood's 3 deposition. 4 "Let me just say at this time a brief 5 stipulation. This is the deposition of David 6 Wheadon taken on behalf of the plaintiffs for 7 purposes of discovery and for use in the trial of 8 the cases heretofore recited. The deposition of 9 Doctor Wheadon is taken by agreement of counsel 10 and by notice. Objection will be made at this 11 time as to any leading questions that Doctor 12 Wheadon's own counsel may put to him or any 13 objection that any lawyer may have to the 14 witness's responses to the questions propounded. 15 All other objections will be reserved until time 16 of court hearing." 17 * * * * * * * * * * 18 COMES DAVID WHEADON, CALLED BY THE 19 PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, WAS 20 DEPOSED AND TESTIFIED AS FOLLOWS: 21 DIRECT EXAMINATION 22 BY MR. SMITH: 23 Q. Would you state your name, 24 please, sir? Page 14 1 A. David E. Wheadon M.D. 2 Q. How old a man are you, Doctor 3 Wheadon? 4 A. I didn't understand you. 5 Q. How old a man are you? 6 A. Thirty-six. 7 Q. Where do you live? 8 A. I live here in Philadelphia. 9 Q. Are you a married man? 10 A. No, single. 11 Q. Have you always been single? 12 A. Uh-huh. 13 Q. How long have you lived in 14 Philadelphia? 15 A. Going on two and a half years. 16 Q. Well, when did you move to 17 Philadelphia? 18 A. In February of 1992. 19 Q. Why did you move to 20 Philadelphia? 21 A. To join my present employer of 22 SmithKline Beecham Pharmaceuticals. 23 Q. What is your job with 24 SmithKline? Page 15 1 A. Vice-president and director of 2 central nervous system and gastrointestinal 3 clinical research. 4 Q. Was that the job you started 5 with SmithKline at? 6 A. I started as group director of 7 central nervous system clinical research. 8 Q. And when did you become 9 vice-president? 10 A. If I remember correctly, in 11 August of 1992. 12 Q. And before that, I believe you 13 worked for Eli Lilly and Company? 14 A. That's correct. 15 Q. How long did you work for 16 Lilly? 17 A. For four and a half years. 18 Q. When did you start and when 19 did you finish? 20 A. Started working with Lilly in 21 June of 1987, and terminated my employment with 22 Lilly in February of 1992. 23 Q. Why did you leave Lilly? 24 A. To take the opportunity Page 16 1 offered to me at SmithKline Beecham. 2 Q. Were you seeking other 3 employment? 4 A. I'm sorry, I didn't 5 understand. 6 Q. Were you seeking other 7 employment while you were at Lilly? 8 A. I was not actively seeking 9 employment at the time I left Lilly. 10 Q. How did it come about that you 11 decided to leave Lilly and go with SmithKline? 12 A. I was contacted by a 13 headhunter operating on the behalf of SmithKline 14 concerning the position I eventually took at 15 SmithKline. 16 Q. Had you expressed to that 17 headhunter previously that you would be open to 18 other employment opportunities? 19 A. No, the headhunter learned of 20 me through other contacts, and subsequently 21 called me at my office at Lilly. 22 Q. At that time, were you making 23 it known, or were you considering changing 24 employment? Page 17 1 A. At that time I had not spoken 2 to any headhunter or individual that I was 3 interested in looking at other employment. 4 Q. But were you at that time 5 interested in looking at other employment? 6 A. At any time, anyone is 7 interested in hearing about new opportunities, so 8 I was open to hearing about anything, but I had 9 not begun an active search for other employment. 10 Q. Were you in any way 11 dissatisfied or unhappy at your employment with 12 Lilly? 13 A. I was very satisfied at Lilly, 14 I was very challenged by my position at Lilly and 15 felt I had a very fulfilling career there. 16 Q. Then why did you leave? 17 A. Again, the opportunity 18 afforded me at SmithKline represented a chance to 19 move up to another level of functioning at 20 perhaps a sooner time than would have been 21 available to me at Lilly. 22 Q. With respect to the size of 23 the two pharmaceutical companies, SmithKline 24 versus Eli Lilly, which is larger? Page 18 1 A. SmithKline Beecham is larger 2 than Eli Lilly. 3 Q. By what degree? 4 A. I don't have the figures in 5 front of me to give relative incomes or sales, 6 profits, what have you, but just in terms of 7 numbers of employees and size of corporation, 8 SmithKline Beecham is a larger corporation than 9 Eli Lilly. 10 Q. Would it be twice as large? 11 A. Again, I don't know the 12 figures well enough to proffer twice, three 13 times, one and a half. 14 Q. Did you work full time for 15 anybody before you joined Eli Lilly and Company, 16 Doctor Wheadon? 17 A. Yes. 18 Q. Who? 19 A. The last year prior to joining 20 Eli Lilly, I was a full-time employee of the 21 Boston Veterans Administration Medical Center, 22 chief resident and ward attending on one of their 23 psychiatric units. 24 Q. Was that part of your training Page 19 1 for medical school? 2 A. That was the end of my 3 residency training, yes. 4 Q. Why don't we get real quickly 5 your educational background starting with when 6 and where you graduated from high school, and 7 then moving through your M.D. training. 8 A. I graduated from St. Stephens 9 Episcopal School in Austin, Texas in 1975. From 10 there I went to Harvard College, graduating in 11 1979, cum laude, in Biology. From there I went 12 to Johns Hopkins Medical School, receiving my 13 M.D. degree in 1983. I then went to Tufts 14 Medical Center in Boston, then an internship in 15 surgery, and then went into psychiatry, finishing 16 my residency in psychiatry in 1987. 17 Q. At Tufts? 18 A. At Tufts, yes. 19 MR. FREEMAN: I think of all your 20 educational experience, he was most impressed 21 with your high school. 22 Q. We Texans have got to stick 23 together, don't we? 24 A. Exactly. Page 20 1 Q. Did you grow up in Austin? 2 A. No, I grew up much to your 3 distaste in Houston. 4 MR. HARRIS: There has to be a clink 5 in everybody's armor. 6 MR. SMITH: Well, we only worry about 7 other cities with football teams. 8 Q. Biology was your undergraduate 9 major at Harvard? 10 A. Uh-huh, yes. 11 Q. Did you take any undergraduate 12 psychology courses at Harvard? 13 A. In the course of undergraduate 14 work in the basic biology courses there was a 15 psychology section of that. I did not take 16 psychology in and of itself as a course, no. 17 Q. And you didn't major or minor 18 in the discipline of psychology? 19 A. Not in undergraduate, no. 20 Q. Did you take -- were there 21 psychiatry courses at Johns Hopkins that you 22 took? 23 A. Yes, that was a requirement. 24 Q. Did you take any courses other Page 21 1 than those required at Johns Hopkins? 2 A. Yes, I did an additional, what 3 we call, senior elective in psychiatry at Johns 4 Hopkins. 5 Q. So that would have probably 6 been 1983 that you took that course? 7 A. '82, '83. 8 Q. So you would have had the 9 basic psychiatry medical school course as well as 10 one elective advanced psychiatry course? 11 A. That's correct. 12 Q. Would it have been considered 13 an advanced course? 14 A. It was additional work 15 following the basic course, so I guess if you 16 wanted to tag it as advanced, I guess it could be 17 considered that. 18 Q. Was there any clinical work in 19 connection with that course? 20 A. Yes. 21 Q. What type of clinical work did 22 you do in connection with that course? 23 A. Inpatient psychiatry. 24 Q. Where was that done? Page 22 1 A. At Johns Hopkins in the 2 Phipp's Clinic, which is the psychiatric portion 3 of Johns Hopkins Hospital. 4 Q. All right. When you went and 5 did your internship at Tufts, did I understand 6 that you started in surgery? 7 A. That's correct. 8 Q. You intended to be a surgeon 9 at that time? 10 A. That's correct, uh-huh. 11 Q. And changed your ideas on that 12 after how long? 13 A. I decided that I was perhaps 14 more interested in things other than spending 15 ninety-nine point nine percent of my life in the 16 operating room in February of my internship. 17 Q. So that would have been -- 18 when did you start your internship? 19 A. We started July 1. Each 20 internship year begins July 1 through June 30th. 21 Q. Why did you choose psychiatry 22 after you had eliminated surgery, any particular 23 reason that you were interested in psychiatry? 24 A. Well, the interest was not Page 23 1 after eliminating surgery, surgery and psychiatry 2 were the two things I was interested in in 3 medical school. So those were the two 4 disciplines I did additional work in in addition 5 to doing additional medical clinical clerkship as 6 well. My decision was to go into surgery over 7 psychiatry. Part way through internship, I 8 decided that I had not made the right decision, 9 and subsequently decided to go back into 10 psychiatry, or to go into psychiatry. 11 Q. And so you did three years in 12 psychiatry at Tufts? 13 A. That's correct. 14 Q. Then did you do fellowship 15 work or any type of postgraduate work after that? 16 A. Again, in my last year of 17 residency as chief resident ward attending -- 18 Q. At Boston V.A.? 19 A. -- at Boston V.A., and then 20 went to Eli Lilly in 1987. 21 Q. Other than that work, that 22 clinical work you did in connection with the 23 advanced course while you were in medical school, 24 and in that clinical work that you did in your Page 24 1 residency, did you -- have you ever done any 2 other clinical work in psychiatry? 3 A. I have not had a private 4 practice, no. I have seen patients during the 5 course of residency and during my chief residency 6 as private patients, but that's within the 7 context of the New England Medical Center or the 8 Boston V.A. 9 Q. When you were at Tufts or in 10 Boston, did you do any work at the McLean 11 Hospital? 12 A. I did not do any training at 13 McLean Hospital, no. 14 Q. Did you go out there to see 15 any patients or anything of that nature? 16 A. No. 17 Q. Did you attend any seminars or 18 anything of that nature? 19 A. If I can recall, I may have 20 been to McLean to attend postgraduate or graduate 21 type seminars, but I can't recall, I have gone to 22 so many. 23 Q. Did you ever take any courses 24 or do any type of study under Doctor Martin Page 25 1 Teicher? 2 A. No. 3 Q. How about Doctor Jonathan 4 Cole? 5 A. No. 6 Q. Are you familiar with those 7 psychiatrists? 8 A. Familiar with those 9 psychiatrists, yes. 10 Q. At the time you were in the 11 Boston area, familiar with the Boston psychiatry 12 community, would you say that Doctor Martin 13 Teicher was held in high regard in that community 14 as a competent psychiatrist? 15 A. At the time I was in Boston, I 16 had not heard of nor had met Doctor Teicher, so 17 he was not a name I was familiar with. 18 Q. Since then, have you come to 19 know that Doctor Teicher is a psychiatrist 20 teaching on the staff of Harvard Medical School 21 who is well regarded in that area? 22 A. Since that time I have come to 23 know Doctor Teicher as a member of the faculty at 24 McLean and Harvard Medical School, yes. Page 26 1 Q. Do you have any criticism or 2 have you heard any criticism of his competence as 3 a professor of medicine at Harvard Medical 4 School? 5 A. I don't have any criticism of 6 his competence as a physician, nor have I heard 7 criticism of his competence as a physician. 8 Q. Same questions with respect to 9 Doctor Jonathan Cole. Do you have any reason to 10 or have you heard any criticism concerning his 11 competence, either as a teacher or as a 12 psychiatrist? 13 A. I have not heard any criticism 14 of Doctor Cole as a teacher nor as a 15 psychiatrist. 16 Q. How did you come to go with 17 Eli Lilly and Company? 18 A. Well, at the time I was 19 finishing my chief residency at the Boston V.A., 20 several opportunities were made available to me, 21 one of which was the opportunity at Lilly, and 22 for a host of reasons I decided to take that 23 opportunity. 24 Q. Can you list some of those Page 27 1 host of reasons, maybe the top three reasons? 2 A. The top three -- the prime one 3 is I, after visiting Lilly, was very impressed 4 with the academic, very scientific rigorous 5 nature of the medical department at Lilly, in 6 addition to the personnel on staff at Lilly. It 7 represented an opportunity for me to continue to 8 be involved with research and not be subjected to 9 the sometime rigorous demands of chasing grants 10 to support your research within academics, which 11 is a reality of academics these days. Also 12 joining Lilly represented an opportunity for me 13 to earn an income, a level of living that would 14 afford me the possibilities to pay back my 15 student loans. 16 Q. Did you consider going into 17 private practice? 18 A. My chief interest was in 19 academics, and so one of the other possibilities 20 was indeed to take a fellowship at McLean working 21 with Doctor Allen Shatzberg in the affective 22 disorders research unit. 23 Q. Any other universities that 24 you expressed an interest to joining as part of Page 28 1 the faculty? 2 A. There was also an offer to 3 remain at Tufts and to remain on staff at the 4 Boston V.A. 5 Q. Did you interview with or send 6 resumes to any other pharmaceuticals? 7 A. I did interview with Dupont 8 Pharmaceuticals, which is now Dupont America. 9 Q. But you chose Lilly over 10 Dupont? 11 A. Yes. 12 Q. Were you offered a job by 13 Dupont? 14 A. Yes. 15 Q. And you started with Lilly in 16 June, 1987, correct? 17 A. That's correct. 18 Q. And at that time you had not 19 done any private psychiatric practice? 20 A. That's correct. 21 Q. Up to the time of June, 1987, 22 had you been involved in any clinical trials in 23 connection with psychoactive medications? 24 A. Yes, I was. Page 29 1 Q. Tell me about those, please, 2 sir. 3 A. The prime trial which I was 4 most involved was a trial, inpatient trial of 5 Haldol. Haloperidol is an antipsychotic used for 6 treating psychotic disorders including 7 schizophrenia. So we were involved in looking at 8 Haldol in comparison to older psychotropic 9 agents, such as Thorazine, in treating psychotic 10 features. 11 Q. When you say we, who are you 12 talking about with respect to we? 13 A. The principal investigator on 14 that trial was Doctor George Arana, who was my 15 supervisor at the Boston V.A. 16 Q. Who makes Haldol? 17 A. McNeil. 18 Q. How long did you participate 19 in that trial? 20 A. Over the course of a year. 21 Q. Was it a one-year trial or did 22 you come in in part of it and work on it for a 23 while and then go on and leave that position? 24 A. The trial had been initiated Page 30 1 at the time I joined the study group, but we 2 completed the enrollment and study portion of the 3 trial by the time I had left. 4 Q. All right. So all the 5 patients who were going to be enrolled were 6 enrolled during the time you were involved in the 7 study? 8 A. That's correct. 9 Q. And they completed their 10 course of treatment as called for under the 11 protocol? 12 A. That's correct. 13 Q. Then you left? 14 A. That's correct. 15 Q. What was your particular 16 function in that study, what did you do? 17 A. My role as chief resident on 18 the unit was to evaluate admissions to the unit 19 for meeting criteria for enrollment into the 20 study or, in some cases, obtaining informed 21 consent from patients to participate in the 22 study, to supervise the nurse clinicians and/or 23 residents who were assigned for doing the rating 24 scales, an example of which is the baseline Page 31 1 psychiatry rating scale or BPRS, it's a standard 2 scale in schizophrenia, and really ensuring that 3 the dictates of the protocol were followed point 4 by point. 5 Q. Were any of those patients 6 depressed or would they have met the SRSM -- 7 DSM-3R criteria for depression or is that part of 8 it? 9 A. We were studying specific 10 psychosis. While some of these patients may have 11 what we call secondary depression, which is sort 12 of a spinoff series of depressive symptoms, our 13 focus was on psychosis. 14 Q. So the Haldol there wasn't 15 being administered as an antidepressant at all? 16 A. No, it was not. 17 Q. And there were not any 18 measurement of increase or decrease in severity 19 of depression in that trial? 20 A. There was not. 21 Q. Was there a measurement of 22 suicidality in that trial? 23 A. There was no specific 24 measurement. A standard question that one asks Page 32 1 in admitting a patient to the inpatient unit is 2 about their various thought processes, including 3 whether or not they had had thoughts about 4 harming themselves. 5 Q. But as far as that being 6 something that was evaluated in the clinical 7 trial, suicidality was not. 8 A. It was evaluated at entry into 9 the trial as one of the exclusion criteria into 10 the trial. 11 Q. And were suicidal patients 12 excluded from that trial? 13 A. Patients who were at the time 14 of evaluation actively suicidal were not included 15 in that trial. 16 Q. But there was no formal 17 questionnaire used to make that determination 18 with respect to whether or not the patient was 19 actively suicidal? 20 A. No, there was no formal 21 questionnaire used, that's correct. 22 Q. Any other clinical trial work 23 that you had done prior to joining Lilly? 24 A. That was my primary clinical Page 33 1 trial work. As I mentioned, in working at the 2 Tufts New England Medical Center there were a 3 number of trials going on, and residents that 4 were covering the emergency room would often see 5 patients. If a patient met criteria for one of 6 the trials that were going on, we would 7 subsequently funnel the patient to the 8 appropriate ward where the trial was ongoing. 9 But the trial I've just described is the one 10 where I was involved from beginning to end 11 essentially. 12 Q. Well, in those other trials 13 where you were funneling patients to the 14 particular investigators, did you ever have an 15 active role in conducting any part of that trial? 16 A. No. 17 Q. Other than seeing that that 18 patient was seen by that particular investigator? 19 A. No. 20 Q. Doctor Wheadon, we met, my 21 name is Paul Smith, I'm from Dallas, Texas, and I 22 represent a number of individuals whose families 23 have been affected as a result of fluoxetine 24 hydrochloride, Prozac. And we're here to take Page 34 1 your deposition and your deposition will be used 2 as evidence in these trials. Do you understand 3 that, sir? 4 A. Yes, I understand that. 5 Q. If I ask you any questions 6 that you don't understand or that are subject to 7 two different interpretations, would you ask me 8 to clarify that question? 9 A. I will do so. 10 Q. Also, it will be necessary 11 that you give an audible yes-no answer so that 12 our court reporter can get that down. 13 A. Okay. 14 Q. You have had an opportunity to 15 discuss the deposition with your attorney here? 16 A. That's correct. 17 Q. And he's given you an idea of 18 the basic rules of a deposition? 19 A. That's correct. 20 Q. Have you had an opportunity to 21 talk with any of the attorneys from Eli Lilly and 22 Company? 23 A. Yes, I have. 24 Q. Who from Eli Lilly have you Page 35 1 talked with? 2 A. Mary Huff and Mister Jim 3 Burns. 4 Q. And when was that? 5 A. With Ms. Huff, yesterday, and 6 with Mister Burns, I can't recall exactly the 7 date. 8 Q. Was it recently? 9 A. It was within the past two to 10 three months. 11 Q. And where did those 12 discussions take place? 13 A. In my office here in 14 Philadelphia. 15 Q. Was there anybody else present 16 at those meetings besides you and Mister Burns 17 and Ms. Huff? 18 A. Yes, there were other lawyers 19 present as well. 20 Q. Were those other lawyers to 21 your understanding attorneys for Eli Lilly and 22 Company? 23 A. The lawyers present were my 24 counsel, Mister Jim Coleman, and outside counsel Page 36 1 for Eli Lilly and Company. 2 Q. Who were the outside counsel 3 for Eli Lilly and Company? 4 A. On one occasion, Mister John 5 McGoldrick, and I'm not remembering who was the 6 other lawyer present. 7 Q. Is he sitting here today? 8 A. No -- oh, was that you, John -- 9 John Brennan? 10 Q. From Mister McGoldrick's 11 office? 12 A. Yes. 13 Q. And that was several months 14 ago that you met with Mister Burns and Mister 15 McGoldrick and Mister Brennan? 16 A. And Mister Coleman. 17 Q. All right. How long did those 18 meetings take place? 19 A. That first meeting took place 20 over the course of roughly three hours. 21 Q. And the meeting with Ms. Huff? 22 A. That took place over the 23 course of, I guess, about eight hours. 24 Q. Did you review any documents? Page 37 1 A. No, I did not. 2 Q. Did any of the attorneys show 3 you any documents -- 4 A. No, they did not. 5 Q. -- to look at? Have you had 6 an opportunity to see any documents in connection 7 with these cases since you left Eli Lilly and 8 Company? 9 A. I have not seen any documents 10 in connection with this case or these cases since 11 I left Eli Lilly. 12 Q. When I say these cases, 13 probably that's not a good term. Have you 14 reviewed any documents in connection with the 15 issues presented by these cases, such as 16 fluoxetine, Prozac, inducing suicidal ideation 17 and behavior or violent aggressive behavior? 18 A. I have not reviewed any 19 documents in association with those topics since 20 leaving Eli Lilly. 21 Q. Did you discuss with any of 22 these attorneys any particular documents? 23 A. I did not discuss any 24 particular documents with these attorneys, no. Page 38 1 Q. Did you discuss any documents 2 with these attorneys? 3 A. I've discussed with these 4 attorneys the Teicher article which is in the 5 American Journal of Psychiatry, the Boston -- the 6 British Medical Journal article edited by Charles 7 Beasley and other authors concerning the 8 assessment of suicidal ideation and behavior in 9 patients on Prozac. 10 Q. During the clinical trials? 11 A. Yes. 12 Q. Did you understand Doctor 13 Beasley's article was limited to Lilly's clinical 14 trial experience? 15 A. Yes, I understood that. 16 Q. Did you understand that Doctor 17 Beasley's article was limited to -- limited to 18 Lilly clinical trial experiments? 19 A. I don't understand your 20 question. 21 Q. That Doctor Beasley's article 22 didn't include all the clinical trial data in 23 connection with suicidality and Prozac. 24 A. My understanding is, both Page 39 1 based on my time at Lilly and in terms of 2 discussions on this article since leaving Lilly, 3 that that study -- that review of studies carried 4 out by Lilly included placebo controlled trials 5 of similar design and similar duration. 6 Q. And those trials were not the 7 only trials in connection with Prozac? 8 A. Those trials were the only 9 trials that were controlled by placebo or 10 accurate comparitor randomized double-blind 11 trials. 12 Q. I understand that. But you're 13 not saying that those were the only trials in 14 which Lilly studied depressed individuals, were 15 they? 16 A. There were other protocols in 17 which Prozac was used that were not controlled 18 double-blind or randomized, that's correct. 19 Q. There were trials outside of 20 the United States that were double-blind placebo 21 controlled trials that weren't even used in 22 Doctor Beasley's article also, weren't there? 23 A. There were trials outside the 24 United States that were double-blind placebo Page 40 1 controlled that were not included in the British 2 Medical Journal article, that's correct. 3 Q. And in Doctor Beasley's 4 meta-analysis? 5 A. In the British Medical Journal 6 article and the meta-analysis upon which that 7 article is based. 8 Q. Do you know why Doctor Beasley 9 did not include the outside U.S. data 10 double-blind placebo controlled trials? 11 A. The European, which you're 12 referring to, double-blind placebo controlled 13 trials, the analyses on those trials had not been 14 completed at the time Doctor Beasley's manuscript 15 was submitted for publication. 16 Q. How do you know that? 17 A. I was at Lilly at that time. 18 Q. All right. Have you been 19 asked to testify as an expert in any of these 20 Prozac cases? 21 A. No, I have not. 22 Q. Any other articles that you 23 discussed with the attorneys concerning these 24 issues? Page 41 1 A. Any other articles? 2 Q. Yes. You mentioned Doctor 3 Teicher's article and the Beasley article. 4 A. We have not discussed in 5 detail, we being myself and the attorneys 6 mentioned earlier, the King-Riddle article, but 7 that article has been mentioned in our 8 discussions. 9 Q. Where is that article 10 published? 11 A. If I remember correctly, that 12 article appeared in the Journal of Adolescent 13 Psychiatry, but I can't recall exactly. 14 Q. Did they bring that up to you 15 or did you mention that? 16 A. I don't recall who mentioned 17 it initially. 18 Q. How was that article brought 19 up? 20 A. In the context of articles 21 that have appeared in the public domain 22 concerning this issue. 23 Q. What is your recollection of 24 the King-Riddle article's conclusion? Page 42 1 A. My recollection of the 2 King-Riddle article is that it was a discussion 3 of a series of cases of adolescents being treated 4 with Prozac in which there was seemingly a focus 5 in these patients on suicidal ideation. 6 Q. Was it an observation that 7 those patients while on Prozac became suicidal? 8 A. One of the offered opinions in 9 the article was that the patient became suicidal 10 after Prozac was initiated as a part of their 11 treatment. 12 Q. With Prozac? 13 A. Other medications were 14 involved in addition to Prozac, but Prozac was 15 one of the medications, yes. 16 Q. And Prozac was appointed as 17 being a potential cause for that suicidality that 18 was seen in those patients being treated with 19 Prozac? 20 A. If I remember correctly, the 21 opinions expressed were that there were several 22 possible explanations for the phenomena described 23 in the cases, one of which is that Prozac may 24 have played a role in the suicidal ideation seen Page 43 1 in those patients. 2 Q. You began work with Lilly in 3 June of 1987, so at that time Prozac was not 4 available to physicians for prescription to the 5 general public? 6 A. That's correct. 7 Q. Had you been involved in any 8 way with any clinical trials in connection with 9 Prozac where you might have been able to 10 administer Prozac prior to June, 1987? 11 A. No, I had not been. 12 Q. In other words, obviously, 13 even though physicians in general couldn't 14 prescribe Prozac until June of 1987, it could be 15 prescribed in the clinical trials, and I assume 16 for particular compassionate uses. 17 A. That's correct. 18 Q. But you were never involved in 19 that? 20 A. That's correct. 21 Q. Did you ever talk with anybody 22 who was involved in that? 23 A. Not prior to my joining Lilly, 24 no. Page 44 1 Q. Had you done any work or done 2 any research of any kind on specific serotonin 3 reuptake inhibitors up until the time you joined 4 Eli Lilly and Company? 5 A. No, I had not done work on 6 specific serotonin reuptake inhibitors prior to 7 joining Lilly. 8 Q. Prior to joining Lilly, did 9 you have any particular interest or did you do 10 any particular work in connection with the mental 11 illness of depression? 12 A. Prior to joining Lilly, I 13 treated depressed patients, and that was the 14 prime association I had had with depression prior 15 to joining Lilly. 16 Q. Now that treatment that you 17 engaged in of depressed individuals prior to 18 joining Lilly would have all been in an academic 19 setting? 20 A. That's correct. 21 Q. It would have never been in 22 private practice? 23 A. Well, again, I saw private 24 patients within the academic setting, so I saw Page 45 1 patients on a weekly basis very similar to how a 2 private practitioner would see patients, but it 3 was at the medical center within the context of 4 the academic setting. 5 Q. And you received no payment 6 for seeing those patients? 7 A. Not directly from the patient, 8 no. 9 Q. And you are not holding 10 yourself out and have never held yourself out to 11 the public as a psychiatrist available for 12 treatment of psychiatric disorders? 13 A. Not outside the confines of my 14 academic affiliations, that's correct. 15 Q. While at Lilly were you 16 allowed to practice psychiatry privately? 17 A. Lilly does not allow 18 physicians to carry on a private practice along 19 with their employment at Eli Lilly, so I did not 20 see patients in a private practice setting while 21 at Lilly. 22 Q. How about here in Philadelphia 23 while at SmithKline Beecham? 24 A. As well, we do not allow Page 46 1 physicians to have a private practice while in 2 full-time employment with SmithKline Beecham. 3 Q. Have you ever prescribed 4 Prozac to any individual? 5 A. No, I have not. 6 Q. Have you ever prescribed any 7 antidepressant to any individual? 8 A. Yes, I have. 9 Q. And that would have all been 10 prior to June, 1987? 11 A. That's correct. 12 Q. I would assume that while you 13 were at Johns Hopkins -- 14 A. That's correct. 15 Q. The Texas is coming out in me. 16 I bet you had trouble moving from Houston to 17 Austin and going up here and calling it right. 18 Don't answer that. 19 A. Okay. 20 Q. While you were at Johns 21 Hopkins in this initial course that you studied 22 with respect to psychiatry, was there an area 23 focused on the mental illness of depression? 24 A. Yes. As a portion of the Page 47 1 course in psychiatry, we did discuss depression, 2 its biological basis, its psychological basis, 3 and the treatment of that disorder. 4 Q. Doctor Wheadon, do you hold an 5 opinion in connection with respect to whether or 6 not depression has a biological basis? 7 A. I certainly believe, based on 8 the studies that I'm aware of, the learnings that 9 I've had in my medical training, that there are 10 types of depression that are clearly biologically 11 based, yes. 12 Q. Can you give us briefly what 13 biological basis there is for some depressed 14 individuals? 15 A. There are a host of studies 16 that have shown that in depressed individuals 17 there are alterations in certain brain chemicals, 18 neurotransmitters, if you will, that seem to 19 underlie the depressive syndrome. Those 20 transmitters are primarily norepinephrine and 21 serotonin. 22 Q. Is that your opinion? 23 A. Yes. 24 Q. Do you feel that individuals Page 48 1 who are depressed suffer from some sort of 2 weakness? 3 A. You would have to define what 4 you mean by weakness. 5 Q. Some defect in character. 6 A. No, I do not believe depressed 7 individuals suffer from a defect in character. 8 Q. Is there any difference with 9 respect to whether or not a depressed individual 10 caused their illness of depression than an 11 individual who has, for instance, diabetes as far 12 as being the cause of their disorder? 13 A. Depressed individuals, like a 14 patient with diabetes, suffers, we believe, 15 certain genetic vulnerabilities to the onset of 16 that illness. 17 Q. And is that because of their 18 neurotransmitters or some alteration in brain 19 chemistry? 20 A. Some alteration in brain 21 chemistry, that's correct. 22 Q. And is it the theory of 23 antidepressant therapy that these particular 24 antidepressants can affect these particular brain Page 49 1 chemicals? 2 A. The theory in treating 3 depression with psychopharmacologic agents is 4 that they in some way alter this imbalance or 5 deficit of the brain chemicals involved in 6 depression. 7 Q. Do you believe that, sir? 8 A. I believe that, yes. 9 Q. That that does occur? 10 A. Yes. 11 Q. And did you have that opinion 12 as a result of your medical school training? 13 A. That's correct. 14 Q. You held that opinion prior to 15 joining Eli Lilly and Company? 16 A. That's correct. 17 Q. Nobody at Eli Lilly and 18 Company convinced you that antidepressant 19 treatment was appropriate for depressed 20 individuals? 21 A. No, that was not a process 22 that happened at Eli Lilly, that's correct. 23 Q. That was a part of your 24 medical training? Page 50 1 A. That's correct. 2 Q. I assume that's a part of 3 medical training given to most medical students 4 throughout the United States. 5 A. That's correct. 6 Q. And you don't have to 7 specialize in psychiatry to be exposed to that 8 concept in medical school? 9 A. That's correct. 10 Q. Do you believe, Doctor 11 Wheadon, or do you have an opinion, sir, that 12 Prozac, fluoxetine hydrochloride, affects brain 13 chemistry in individuals? 14 A. The mechanism of action of 15 Prozac is that it blocks the reuptake of 16 serotonin, and as such increases the amount of 17 serotonin available in what we call the synaptic 18 cleft, and that is the basic mechanism of action. 19 Q. Do you believe that occurs? 20 A. Yes. 21 Q. And do you believe that 22 produces direct physiological changes in the 23 brain chemistry of individuals? 24 A. That corrects the deficit Page 51 1 present in depressed individuals, the deficit 2 being a lack of serotonergic functioning 3 underlying their depression. 4 Q. Okay. So does that mean that 5 it's your opinion, Doctor Wheadon, that if an 6 individual does not have a deficit in the 7 serotonin system, that Prozac will not have an 8 effect on that individual's serotonin 9 availability? 10 A. If a person that is not 11 depressed and does not have a deficit in 12 serotonin is given a serotonin reuptake inhibitor 13 like Prozac, you may have an intermediate 14 increase in serotonin in the cleft. But because 15 of feedback mechanism, the balance of serotonin 16 will be achieved because of certain feedback 17 loops that exist in the central nervous system. 18 Q. But that occurs only after you 19 have had the increase of serotonin in the 20 synaptic cleft? 21 A. Exactly. 22 Q. That's in response to this 23 higher than had been seen previously level of 24 serotonin in the synaptic cleft? Page 52 1 A. That's correct. 2 Q. And that occurs in individuals 3 whether or not they were depressed? 4 A. I don't understand that 5 question. 6 Q. Well, the response, that is 7 the alteration of availability of serotonin in 8 the synaptic cleft, is going to occur regardless 9 of whether or not an individual is depressed or 10 not depressed? 11 A. You have a different 12 situation, depressed individual versus a 13 nondepressed individual. If you have an existing 14 deficit and you give a serotonin reuptake 15 inhibitor like Prozac, you bring serotonergic 16 functioning up to, quote, a normal level, so the 17 feedback mechanism doesn't kick in, as I 18 described earlier, whereas a nondepressed 19 individual where you're operating at a normal 20 serotonergic term, you block the serotonin 21 reuptake, you do have an early sort of kick in of 22 the feedback mechanism. So you can't put both in 23 the same camp, I guess, is what I'm saying. 24 Q. What scientific data is there Page 53 1 to establish that, Doctor Wheadon? 2 A. There's scientific data 3 looking at the effect of serotonin reuptake 4 inhibitors in animals, lab mice, what have you. 5 There are scientific data looking at the 6 serotonergic activity in normal volunteers with 7 serotonin reuptake inhibitors as well as in 8 patients. The problem is is that you can't take 9 an aliquot of cerebrospinal fluid out of the 10 brain and know exactly what's going on in humans, 11 in the live human, as you can with animals, mice, 12 what have you. 13 (DISCUSSION OFF THE RECORD.) 14 Q. Doctor Wheadon, there are 15 fourteen individuals sitting around this table. 16 MR. COLEMAN: You could have used any 17 number you wanted. 18 Q. Wouldn't it be accurate that 19 in all scientific probability each one of us 20 would have a different serotonin level in our 21 brain? 22 A. What you're asking is do we 23 all sitting in this room have the same level of 24 serotonergic functioning? Page 54 1 Q. Yes, sir. 2 A. And the best of my 3 understanding of a very complicated science, the 4 answer is no, we don't all have exactly the same 5 level of serotonin in the brain, the same level 6 of serotonergic functioning. 7 Q. The level of serotonin in the 8 brain and the level of serotonin functioning are 9 absolutely two different things, aren't they, 10 Doctor? 11 A. You have to explain to me what 12 you mean by absolutely two different things. 13 Q. They are two different things. 14 A. The level of serotonin in the 15 brain and serotonergic functioning are related 16 phenomena, but you are correct that serotonin -- 17 serotonergic functioning involves more than just 18 serotonin reuptake blockade. 19 MR. SMITH: I love it when doctors say 20 that you are correct. 21 Q. Before I move on, Doctor, in 22 fact probably each of us will have a different 23 level of serotonin in our brain now than we did 24 when we got up this morning. Page 55 1 A. There is what we call a 2 circadian fluctuation in the level of serotonin 3 based on a series of things that go on in our 4 bodies, yes. 5 Q. And nobody knows exactly how 6 that functions in any particular individual 7 either? 8 A. Without doing very, very 9 rigorous intensive sort of blood samplings, what 10 have you, no, no one can say at any one point in 11 time what the level of serotonin is in your body 12 and what your serotonergic functioning is. 13 Q. In fact, Doctor, if you took 14 in connection with blood sampling, you really 15 can't tell availability of serotonin in the 16 synaptic cleft from availability of serotonin in 17 the plasma and blood either, can you? 18 A. That's correct. 19 Q. There's no relationship 20 between the two? 21 A. That's correct. 22 Q. So by that, you can't take a 23 blood test from me, a simple blood test, and 24 determine how much serotonin I have at the Page 56 1 synaptic cleft, can you? 2 A. Not by a blood test. But we 3 can take, for example, as I mentioned, cerebral 4 spinal fluid, and look for certain things like 5 breakdown products of serotonin which is known as 6 five hydroxyindoleacetic acid, five HIAA, and 7 make some assumptions about the level of 8 serotonergic function. 9 Q. But that's not done in 10 prescribing specific serotonin reuptake 11 inhibitors, is it, Doctor? 12 A. That's not done in prescribing 13 serotonin reuptake inhibitors, no. 14 Q. In ninety-nine point nine 15 percent of the time that a psychiatrist 16 prescribes Prozac, he doesn't do that, does he? 17 A. In ninety-nine point nine 18 percent of the time of the psychiatrist 19 prescribing any antidepressant he does not do 20 that. 21 Q. And in ninety-nine point nine 22 percent of the time that a general practitioner 23 prescribes Prozac, he doesn't do a lumbar 24 puncture, does he? Page 57 1 A. A general practitioner does 2 not do a lumbar puncture in prescribing any 3 antidepressant in general, no. 4 Q. When you came to Lilly, what 5 was your first job function or job title? 6 A. I joined Lilly in June of 1987 7 as a clinical research physician, associate 8 clinical research physician. 9 Q. And how long did you hold that 10 position? 11 A. I was an associate clinical 12 research physician for roughly a year, year and a 13 half, at which time I was designated a clinical 14 research physician. 15 Q. So you would have been an 16 associate clinical research physician until what? 17 A. Fall of '88. 18 Q. Then your next position was 19 clinical research physician? 20 A. That's correct. 21 Q. And how long did you hold that 22 position? 23 A. Until the time I left Lilly. 24 Q. Which was February, 1992? Page 58 1 A. That's correct. 2 Q. Who was your immediate 3 supervisor during the period of time that you 4 were an associate clinical research physician? 5 A. At the time I joined Lilly, my 6 immediate supervisor was Doctor Dan Masica. 7 Q. And how long did he continue 8 to be your immediate supervisor? 9 A. Doctor Masica was my 10 supervisor until the time that Doctor Gary 11 Tollefson joined the company, I can't remember 12 exactly the date. 13 Q. Well, had Doctor Tollefson 14 joined by the time you became a clinical research 15 physician? 16 A. No, he had not. 17 Q. So it was after February of 18 1992 that Doctor Tollefson became your 19 supervisor? 20 A. No, I left the company in 21 February, 1992. 22 Q. I'm sorry, it would have been 23 after the Fall of 1988? 24 A. That's correct. Page 59 1 Q. Anybody else that you reported 2 to during your period at Lilly? 3 A. No, just Doctor Masica and 4 Doctor Tollefson. 5 Q. When you came on with Lilly, 6 how many clinical research physicians, both 7 associate and the next level, were there in the 8 CNS division? 9 A. I don't recall exactly the 10 number of physicians at the time I joined Lilly, 11 I just remember I did have one other supervisor. 12 Q. All right. 13 A. Actually at the time I joined 14 the company, my supervisor was Doctor Mike 15 Draper. 16 Q. D-R-A-P-E-R? 17 A. D-R-A-P-E-R. 18 Q. Was he a psychiatrist? 19 A. No, he was not, he was an 20 endocrinologist. 21 Q. How long was Doctor Draper 22 your supervisor? 23 A. For just a few months. 24 Shortly after joining there was a reorganization Page 60 1 of the medical group, CNS was separated from 2 endocrinology, and Doctor Masica took over as the 3 head of the CNS group. 4 Q. Is Doctor Draper still with 5 Lilly? 6 A. No, he is not. 7 Q. Where is he now? 8 A. I have no idea. 9 Q. Who were you working with in 10 addition to Doctor Masica when you started with 11 Lilly? 12 A. Doctor Joe Wernicke. 13 Q. And I'm talking about doctors. 14 A. Doctor Joe Wernicke, Doctor 15 John Heiligenstein, Doctor Masica, those were the 16 principle physicians I worked with at the time I 17 joined the company. 18 Q. When did Doctor Beasley come 19 on? 20 A. Doctor Beasley joined shortly 21 after I did. I joined about a month before 22 Doctor Beasley joined. 23 Q. Who else joined during that 24 time? Page 61 1 A. When you say during that time, 2 what time frame are you referring to? 3 Q. From June, 1987 until you left 4 in February, 1992. 5 A. A number of people joined 6 during that time. 7 Q. I'm talking about physicians 8 that were clinical research physicians who were 9 overseeing work in any way on fluoxetine 10 hydrochloride, Prozac. 11 A. A number of people joined 12 during that time. 13 Q. Give me some names. 14 A. Also at the time I joined, I 15 forgot Doctor Louise Levine was also a member of 16 the CNS group. During the course of my tenure at 17 Lilly, physicians joining the CNS group included 18 Doctor David Goldstein, as I mentioned, Doctor 19 Beasley, Doctor Jamie Street, Doctor Amy Chappel, 20 Doctor Jim Kotsanos, Doctor Winston Satterlee 21 joined the CNS group from another medical group, 22 Doctor Tollefson, as I mentioned, joined the CNS 23 group, Doctor Robert Thompson joined the CNS 24 group, but in an international capacity. Page 62 1 Q. Anyone else that you can think 2 of? 3 A. These are the principle names 4 I can recall. 5 Q. Doctor Amy Chappel, I assume 6 that's a she? 7 A. Yes. 8 Q. Did she work on Prozac? 9 A. She did not work directly on 10 Prozac, no. 11 Q. Did she work indirectly on 12 Prozac? 13 A. If anything, she may have 14 provided cross coverage if there were phone calls 15 of a medical nature. 16 Q. Did Doctor Satterlee do any 17 work on Prozac? 18 A. Doctor Satterlee was involved 19 at the time I left with perhaps one or two Prozac 20 protocols, fluoxetine protocols. 21 Q. You did mention Doctor 22 Weinstein? 23 A. I beg your pardon? 24 Q. Doctor Weinstein, Weinstein, Page 63 1 Allen Weinstein? 2 A. That's correct. 3 Q. Did you work with him any? 4 A. I worked with Allen in his 5 capacity as vice-president of the international 6 medical group, that's correct. 7 Q. Did you begin working on 8 Prozac immediately upon coming with Lilly? 9 A. My first project involved an 10 unapproved compound in schizophrenia, but I very 11 shortly thereafter did get involved in some 12 Prozac work, yes. 13 Q. All right. What was the first 14 Prozac work you did? 15 A. The first Prozac work was 16 initiating clinical trials in obsessive 17 compulsive disorder. 18 Q. And when did you begin that 19 work? 20 A. Work on that began, as best I 21 can recall, late '87, early 1988. 22 Q. Okay. So at that time had 23 Prozac received FDA approval for marketing? 24 A. My initial work on the Page 64 1 protocols for obsessive compulsive disorder 2 predated the final FDA approval of Prozac for 3 depression. 4 Q. What was -- was that the first 5 work you did was design a protocol for those 6 clinical trials in OCD? 7 A. It's hard to parcel 8 specifically that way because as one of the 9 medical group, I was involved with helping out in 10 the last days of preparing for Prozac approval, 11 helping prepare for that. 12 Q. What did you do in connection 13 with that? 14 A. Provide assistance in 15 reviewing reports, manuscripts, promotional 16 launch materials, that sort of thing. 17 Q. What did you have to do in 18 connection with that? I mean you're a medical 19 doctor, psychiatrist, what did they need you to 20 do in connection with getting the drug approved? 21 A. In connection with getting the 22 drug approved, it's just a matter of a lot of 23 paperwork back and forth concerning data reports 24 on clinical trials, review of summaries. The FDA Page 65 1 asked us to provide a summary basis for approval, 2 which is a summary document looking at all the 3 clinical trials that were a part of the NDA, just 4 things of that nature. 5 Q. Okay. What work did you do on 6 the summary basis of approval? 7 A. I assisted with reviewing the 8 write up of the various sections of the summary 9 basis of approval, editing, proofreading, double 10 checking clarity, that sort of thing. 11 Q. Did you have any scientific 12 input into that document? 13 A. At the time I joined Lilly, 14 the bulk of the NDA and the bulk of the work for 15 FDA approval had been accomplished. So again, it 16 was more from an assistance in editorial 17 proofreading, clarity check, things along those 18 lines. 19 Q. Any work on safety in 20 connection with that document that you did? 21 A. Any work on safety would have 22 again involved editing, proofreading, clarity 23 check, things of that nature. 24 MR. SMITH: Let's take a break. Page 66 1 (A SHORT RECESS WAS TAKEN.) 2 Q. When you talked with Ms. Huff 3 yesterday, did Ms. Huff advise you concerning any 4 of the testimony that had been given in these 5 cases up to now? 6 MR. FREEMAN: I object to you going 7 into anything that occurred when he was being 8 prepared for his deposition. His attorney was 9 present at all times, and I think the attorneys 10 that represented him and Lilly were present and 11 representing SmithKline and him were present. So 12 he shouldn't answer any questions about any 13 advice that anybody gave him. 14 Q. I'm not asking you for advice. 15 Ms. Huff is not representing, you're here 16 represented by SmithKline counsel, are you not? 17 A. I'm represented by Mister 18 Coleman, correct. 19 Q. And Mister Coleman is not an 20 employee of Eli Lilly and Company? 21 A. That's correct. 22 Q. And not an attorney for Eli 23 Lilly and Company? 24 A. I cannot answer that. Page 67 1 Q. Well -- 2 A. I'm not aware of Mister 3 Coleman's associations outside of representing me 4 and SmithKline Beecham. 5 Q. And Mister Coleman certainly 6 can represent anybody employed by Eli Lilly and 7 Company. 8 MR. COLEMAN: I did ask the question 9 yesterday whether or not Lilly attorneys believed 10 this conversation was privileged, because I did. 11 MR. SMITH: You did not? 12 MR. COLEMAN: I did believe it, I 13 expected that it was privileged and they said 14 that that had already been determined in this 15 litigation, that former employees of Lilly who 16 were talked to by Lilly attorneys were covered by 17 privilege. That's my understanding of what had 18 happened in this case. 19 MR. FREEMAN: That's what Judge Godish 20 ruled. 21 MR. SMITH: Judge Godish ruled only in 22 connection when the attorneys for Eli Lilly said 23 they were representing Doctor Zerbe. Here Doctor 24 Wheadon was being represented by Mister Coleman Page 68 1 and was not being -- 2 MR. FREEMAN: I understood that we 3 were representing him as well was my 4 understanding of it. 5 MR. SMITH: Well, your objection is 6 noted. 7 Q. Did Ms. Huff advise you 8 concerning the testimony that had been elicited 9 up to date? 10 MR. MYERS: He's not required to 11 answer that. 12 MR. COLEMAN: I'm going to instruct 13 him not to answer on the representations of 14 Lilly's attorneys that were already ruled in this 15 case. 16 MR. HARRIS: To the extent that there 17 may be an attorney-client privilege -- 18 MS. ZETTLER: Absolutely no attorney 19 client privilege. 20 MR. MYERS: Just so the record is 21 clear, we're representing Doctor Wheadon for 22 purpose of his deposition because the testimony 23 he's going to give today concerns his former 24 employment with Eli Lilly and Company. Mister Page 69 1 Coleman is here for Doctor Wheadon because he 2 represents Doctor Wheadon's employer, and the 3 employer happens to be, among other things, a 4 competitor of Eli Lilly and Company, and that's a 5 relationship between the lawyers and other 6 witnesses, and to that extent, I believe that 7 Judge Godish, the ruling that he made during 8 Doctor Zerbe's deposition applies. 9 MR. SMITH: We disagree with that 10 interpretation, and, Counsel, are you -- 11 MR. COLEMAN: I will instruct the 12 witness not to answer based on the 13 representations made to me by Lilly's attorneys 14 that that is the rule of the case. I, of course, 15 can't take a position that's that's the case 16 because we're not involved in the case. 17 MS. ZETTLER: Certify the question. 18 (QUESTION CERTIFIED.) 19 Q. I think before the break you 20 told me that your first work in connection with 21 Prozac was in clinical trials in connection with 22 obsessive compulsive disorders, is that correct? 23 A. That's correct. 24 Q. What work did you do in Page 70 1 connection with those clinical trials? 2 A. The writing of the protocol 3 for the study of fluoxetine and the treatment of 4 obsessive compulsive disorder, working with other 5 Lilly personnel in terms of lining up 6 investigators to carry out the protocol, and then 7 monitoring the trial once it had begun -- or 8 trials, I should say. 9 Q. Were you the medical monitor 10 on that trial? 11 A. That's correct. 12 Q. Who was the principal 13 investigator on that trial. 14 MR. MYERS: Excuse me? 15 MR. FREEMAN: There's a 16 confidentiality on that. Very specifically, he's 17 not required to give any names of clinical 18 investigators. 19 MR. SMITH: Could you give me the 20 courtesy of deciding which one of you is going to 21 be making the representation of Lilly here? 22 MR. FREEMAN: He's not to give out any 23 clinical investigators' names, that's clear all 24 along. Page 71 1 MS. ZETTLER: Certify it. 2 (QUESTION CERTIFIED.) 3 Q. Where was that trial held, 4 where were the sites of that trial? 5 A. A number of sites throughout 6 the country. 7 Q. What cities? 8 A. I quite honestly cannot recall 9 exactly the cities at this time. 10 Q. Do you recall any of the 11 cities, Doctor Wheadon? 12 A. At least one of the cities was 13 Miami, Florida. 14 Q. Was Doctor Goldstein the 15 investigator in Miami? 16 MR. FREEMAN: Same objection. He's 17 not required to answer that, he's not to give any 18 names of clinical investigators. 19 Q. Was that study ever published? 20 A. I'm not aware that the results 21 of that study have been published. 22 Q. Was that study reported to the 23 Food and Drug Administration? 24 A. Yes, it has been. Page 72 1 Q. Has there been a final report 2 concerning that study? 3 A. Yes, there has been. 4 Q. Did you prepare the final 5 report or did you oversee a preparation? 6 A. I played a role in the 7 preparation of that final report, yes. 8 Q. Were you the medical monitor 9 in connection with that study throughout the 10 course of that study? 11 A. Yes, I was. 12 Q. That was a study that was 13 begun and completed during your tenure with 14 Lilly. 15 A. That's correct. 16 Q. What other cities do you 17 recall as being sites of that study? 18 A. New Haven -- again, to be 19 honest with you, to be particular beyond that, 20 I've worked with so many trials in so many 21 cities, I cannot recall beyond those two cities. 22 Q. How many patients were 23 enrolled in that study? 24 A. This encompassed two separate Page 73 1 trials. The total enrollment in the two trials 2 was on the order of four hundred patients. 3 Q. When you say there was two 4 trials, does that mean there was two different 5 protocols? 6 A. One protocol, two different 7 trials directed by the same protocol. 8 Q. All right. What was the 9 difference in the two trials? 10 A. The centers involved. 11 Q. You mean it was exactly the 12 same study, it was just at two sites? 13 A. No, that's not correct. 14 Q. Help me. 15 A. Exactly the same protocol, but 16 the investigators were divided up into two 17 different groups, trial A, if you will, and trial 18 B, composed of different investigators, but the 19 same protocol. 20 Q. And then the results of trial 21 A and B were pooled together. 22 A. No, they were analyzed 23 separately. 24 Q. Why? Page 74 1 A. For approval of compounds by 2 the FDA you need to have two efficacy trials, so 3 two independent trials with two independent 4 assessments of efficacy. 5 Q. Well, you say there was two 6 trials with two investigators, you name two 7 cities, Miami, Florida and New Haven, 8 Connecticut. Would it be safe to assume that 9 there weren't any other sites for any studies 10 under that trial or under that protocol? 11 A. You made an incorrect 12 statement. There were two trials with two groups 13 of investigators, multi-center trials. Each 14 trial, trial A, trial B, had multiple centers. 15 Q. All right. When was the study 16 begun and when was it completed? 17 A. I cannot recall those dates. 18 Q. Were patients who were serious 19 suicidal risks included or excluded from those 20 studies? 21 A. One of the exclusions -- one 22 of the exclusion criteria for the trial, trials, 23 was that patients who at evaluation posed a 24 serious suicidal risk were excluded. Page 75 1 Q. Do I take it by that that all 2 of those studies were outpatient studies? 3 A. That's correct. 4 Q. Do you recall whether or not 5 there were any reports or any adverse experiences 6 reported by any investigators during that 7 obsessive compulsive trial of suicidality or 8 aggressive violent behavior? 9 A. When you say reports by any 10 investigator of suicidality or aggressive violent 11 behavior, what do you mean? 12 Q. Well, let's start with where 13 there would have been a 1639 submitted in 14 connection with that particular adverse 15 experience. 16 A. I cannot recall explicitly 17 that a 1639 was filed from that trial concerning 18 those two terms, suicidality or violent behavior. 19 Q. How about anxiety or 20 agitation? 21 A. In light of the fact that 22 obsessive compulsive disorder is an anxiety 23 disorder, there probably was a report or reports 24 of anxiety as a treatment emergent symptom during Page 76 1 the course of the trial. 2 Q. How about nervousness, were 3 there any reports on nervousness that occurred as 4 treatment emergent symptoms during that trial 5 that you recall? 6 A. Again, that is a common 7 occurrence in this disorder, so yes, there were 8 reports of nervousness during the trial. 9 Q. Were the investigators advised 10 in connection with respect to whether or not to 11 report a worsening of obsessive compulsive 12 disorder as an adverse event? 13 A. The investigators were advised 14 as a standard policy for any protocol carried out 15 by Lilly, any worsening of symptoms that were 16 present at baseline were to be viewed as an 17 adverse event and reported as such. 18 Q. What was the rationale for 19 that decision? 20 A. That's a standard way of 21 collecting adverse events in the industry as 22 mandated by the FDA. 23 Q. Well, is that something that 24 is scientifically expected in a clinical trial Page 77 1 that you will see worsening of symptoms? 2 A. I wouldn't say that that's 3 something that's scientifically expected, it's 4 something that's required to collect, that is 5 whether or not symptoms get worse while patients 6 are in the trial. 7 Q. Well, I guess the reason for 8 my question is obviously you don't expect that 9 there be one hundred percent drug efficacy in all 10 patients, do you? 11 A. No, you do not expect one 12 hundred percent drug efficacy in all patients, 13 that's correct. 14 Q. And in many patients with 15 obsessive compulsive disorders, as a natural 16 progression of their illness some of these 17 symptoms get worse, correct? 18 A. In some patients, a worsening 19 of symptoms associated with obsessive compulsive 20 disorder can be seen, that's correct. 21 Q. In other words obsessive 22 compulsive disorder is not a disorder where there 23 is necessarily stability in symptoms, that they 24 remain stable? Page 78 1 A. Depending on the individual 2 patient, there may be a very stable level of 3 symptoms, and there may be exacerbation of 4 symptoms. 5 Q. Just as part of the course of 6 the disease, this exacerbation may occur? 7 A. That's correct. 8 Q. As opposed to any outside 9 portions. 10 A. That's correct. 11 Q. And that's the reason for my 12 question as to why you were reporting worsening 13 of symptoms as adverse events as opposed to 14 merely lack of efficacy. 15 A. Again, standard practice, 16 regardless of the disease under study, if 17 compared to baseline, baseline being when the 18 patient enters into the trial, if there is 19 worsening of symptoms, that is collected as an 20 adverse event with no assumption of what might be 21 causing that worsening of symptoms. 22 Q. So does that mean if you're 23 doing a depression study in connection with an 24 antidepressant, that if an individual becomes Page 79 1 more depressed over the course of the clinical 2 trial, you're going to report that increasing 3 depression as an adverse event, Doctor Wheadon? 4 A. Not necessarily in the context 5 of depression. When we were discussing obsessive 6 compulsive disorder, we were discussing, I 7 thought, specifically things like anxiety and 8 nervousness. 9 Q. Uh-huh. 10 A. If those things get worse, 11 from baseline, that is captured as an adverse 12 event. If the patient's compulsive ritual, let's 13 say if a patient does hand washing, if that 14 worsens, you're quite correct, that's the disease 15 under study and that is not captured as an 16 adverse event. But if anxiety, nervousness, sort 17 of satellite symptoms, not the core components of 18 OCD, gets worse from baseline, that is captured 19 as an adverse event. Now going to depression, 20 depression often is associated with anxiety. 21 Anxiety symptoms can often be seen in patients 22 with depression. Anxiety, however, is not one of 23 the core nine symptoms we look for in diagnosing 24 depression by DSM-3R. So if anxiety worsens Page 80 1 during the course of treatment, that is captured 2 as an adverse event. If the patient's depressed 3 mood gets worse during the course of treatment, 4 that's the disease under study, it's a core 5 symptom of the disease under study, and that is 6 not captured as an adverse event. 7 Q. Why wouldn't you consider that 8 increased anxiety is just an increase in the 9 severity of the depression if you're studying 10 depression? 11 A. Remember we're utilizing 12 rigorous scientific paradigms. You have the core 13 nine symptoms of depression, you have anxiety as 14 sort of a satellite associated symptom. In terms 15 of defining the disease under study, you're 16 looking at the core. If the satellite symptom -- 17 it very well may get worse because of the disease 18 under study, because of depression. But because 19 it's not a designated core symptom, that is 20 captured as an adverse event. 21 Q. And that's because the 22 anxiety, if you're studying depression, might be 23 a part of depression, but it might be caused by 24 some other event, isn't that correct? Page 81 1 A. I would say that the reason 2 why we parcel it out that way is based on what 3 you just said, that's not what drives that 4 process. 5 Q. I understand that, but from a 6 practical standpoint, you may see anxiety in 7 depression, correct? 8 A. That's correct. 9 Q. But anxiety isn't one of the 10 nine core symptoms of depression, correct? 11 A. That's correct. 12 Q. So you capture increased 13 anxiety as an adverse event? 14 A. That's correct. 15 Q. But if you had increased 16 weight loss in a depressed individual, you would 17 not necessarily characterize that as an adverse 18 event because weight loss is one of the nine core 19 symptoms of depression, is that right? 20 A. That's not necessarily 21 correct. 22 Q. Okay. Let's say insomnia 23 then, isn't insomnia one of the nine core 24 symptoms of depression? Page 82 1 A. That's correct. 2 Q. Are you measuring -- are you 3 capturing reports of insomnia as an adverse 4 event? 5 A. It depends on the level of 6 change in insomnia. So if a patient presents as 7 insomnia as a core symptom, okay, and that 8 insomnia stays basically at the same level, that 9 is not necessarily captured as an adverse event. 10 If the patient comes in and says over the past 11 week I have not been able to fall asleep at all, 12 whereas before I started the trial I was able to 13 fall asleep after about forty-five minutes, that 14 could conceivably be captured as an adverse event 15 or would be captured as an adverse event. 16 Q. Because that particular type 17 of insomnia might be related to the drug? 18 A. Or may be related to the 19 disease, it's hard to parcel out. 20 Q. But that's the distinction 21 there is. There you see an individual at 22 baseline who is not necessarily demonstrating 23 part of the core symptoms of the disease, that is 24 insomnia, correct? Page 83 1 A. That's correct. 2 Q. But after you go into 3 treatment and start administering the particular 4 drug, all of a sudden you see that increasing, 5 correct? 6 A. That's correct. 7 Q. So you record that as an 8 adverse event. 9 A. That's correct. 10 Q. Because that may be very well 11 something that is related to the drug? 12 A. Or related to the illness. 13 You can't decide which. 14 Q. What do you do then, Doctor, 15 to make that decision? 16 A. When you say what do I do 17 then, it's nothing that I do, it's the clinician 18 that's treating the patient that's recording that 19 adverse event. 20 Q. All right. But what 21 instructions do you as the medical monitor give 22 the investigator in recording that adverse event? 23 A. The instructions are as I 24 mentioned, if there's a clear change from Page 84 1 baseline, that would be captured as an adverse 2 event. 3 Q. How do you record baseline, is 4 that just something that's left to the 5 investigator's judgment? 6 A. At baseline we ask the 7 investigator to collect symptoms present at 8 baseline, whatever it may be. It may be 9 headache, it may be insomnia, it may be a 10 depressed mood, it may be upper respiratory 11 infection. Whatever the patient in walking 12 through the door presents with, those are to be 13 captured at baseline. 14 Q. And if they get worse, even if 15 they are part of a core symptom of depression, 16 then they're to be recorded as an adverse event? 17 A. Exactly. Now there are some 18 exceptions. For example, as we mentioned in the 19 case of obsessive compulsive disorder, the hand 20 washing as sort of a clear core part of the 21 disease, that wouldn't necessarily be captured as 22 an adverse event. In depression, depressed mood, 23 one of the two things that you have to have in 24 depression, depressed mood gets worse, that may Page 85 1 not be captured as an adverse event because it's 2 part of the disease under study. In the examples 3 you cited very well, insomnia, weight loss, those 4 sorts of sort of down-the-cascade symptoms, 5 should or may be captured as an adverse event 6 depending on the change from baseline. So if the 7 patient comes in a week after entering in the 8 study and they've lost one pound, that may not be 9 captured as an adverse event or viewed as an 10 adverse event by the clinician. 11 Q. What if after three weeks 12 they've lost five pounds? 13 A. Again, that may or may not, 14 depending on what the patient has been doing. If 15 the patient has been dieting -- 16 Q. Let's assume specifically. 17 A. Then that in the clinician's 18 mind probably would be captured as an adverse 19 event. 20 Q. Then what do you do as a 21 medical monitor in making a determination with 22 respect to whether or not that particular adverse 23 event was causally related to the use of the drug 24 under study? Page 86 1 A. The sorts of adverse events 2 we've been discussing, weight loss, insomnia, 3 anxiety, nervousness, don't require a formal 4 assignment of causally related or not. 5 Q. All right, why? 6 A. They're events that happen 7 during the course of the study. At the end of 8 the study, analyses are done looking at the rate 9 of occurrence of these events in the placebo 10 controlled group compared to the rate of 11 occurrence of these events in the active 12 controlled group. So in the case of the OCD 13 study, placebo or Prozac, what was the percent of 14 patients that complained of the occurrence of 15 insomnia or worsening of insomnia, placebo versus 16 fluoxetine. If those percentages are roughly the 17 same, then a causal relationship between Prozac 18 and the adverse event is not likely because it's 19 basically the same rate as the placebo group. 20 Q. What if it's not the same? 21 A. Let's say in the case of -- 22 again, looking at insomnia, your placebo rate may 23 be ten percent, and the rate in the active 24 treatment group may be twenty percent, you then Page 87 1 have some reason to believe that there may be a 2 causal relationship between your active treatment 3 and the occurrence of insomnia. 4 Q. All right. Prozac does cause 5 insomnia in some individuals. 6 A. The clinical trials have 7 shown, based on comparisons like I discussed, 8 that Prozac in some individuals can cause 9 insomnia, that's correct. 10 Q. Why is that that Prozac causes 11 insomnia in some individuals? 12 A. I really can't explain exactly 13 why Prozac causes insomnia in some individuals. 14 Q. I mean Prozac is even 15 recommended to be prescribed to be taken in the 16 morning, is it not? 17 A. It may be taken in the morning 18 or the evening. 19 Q. Well, it's recommended that it 20 be given in the morning, isn't it? 21 A. If I remember the prescribing 22 information correctly, that is a recommendation, 23 that's correct. 24 Q. And the reason for that is Page 88 1 because Prozac causes insomnia in some 2 individuals. 3 A. That is a reason for that 4 recommendation, but by the same token, it can 5 cause somnolence or somnolence has been seen in 6 some individuals in which case you take it at 7 bedtime. 8 Q. But in the -- it's more likely 9 to cause insomnia than somnolence, isn't it? 10 A. I can't make a prediction one 11 way or the other in any one individual. 12 Q. I understand that, but it's 13 generally recommended to be prescribed in the 14 morning, isn't it, Doctor Wheadon? 15 A. That's what's in the labeling, 16 that's correct. 17 Q. And the reason for that is 18 because Lilly and the Food and Drug 19 Administration has decided that there were enough 20 patients that Prozac caused insomnia that it 21 would be better to have all patients taking it in 22 the morning initially. 23 A. I can't comment on the 24 reasoning because I wasn't present at the time Page 89 1 that that particular issue was discussed 2 concerning the labeling. 3 Q. Well, that makes sense, 4 doesn't it, though, Doctor? 5 A. The way you put it, that if a 6 number of patients would have insomnia, taking it 7 in the morning does make sense, yes. 8 Q. And in connection with your 9 comments with respect to somnolence, the fact 10 that it's recommended generally to be taken in 11 the morning means that in more instances it 12 causes insomnia than somnolence, doesn't it? 13 A. If I remember correctly, the 14 rate, the occurrence rate of somnolence as 15 compared to insomnia is less, that's correct. 16 Q. So the answer to my question 17 is that's the reason you prescribed it -- it's 18 recommended to be prescribed in the morning? 19 A. That's an assumption. Again, 20 I was not present when that actual recommendation 21 was made in the labeling. 22 Q. Would you agree with me that 23 that's a reasonable assumption, Doctor Wheadon? 24 A. I think that's an assumption Page 90 1 that is not out of reason, no. 2 Q. Do you have an opinion, Doctor 3 Wheadon, concerning whether or not Prozac causes 4 insomnia in some individuals who are depressed? 5 A. I think Prozac can cause, as a 6 side effect, insomnia in some individuals, that's 7 correct. 8 Q. Do you believe or do you have 9 an opinion that Prozac can cause weight loss in 10 some individuals? 11 A. I do not believe Prozac in and 12 of itself causes weight loss in some individuals. 13 Q. Do you have an opinion 14 concerning whether or not Prozac causes a 15 decrease in appetite in some individuals? 16 A. One of the adverse events that 17 have been seen in clinical trials is a curbing of 18 the appetite. 19 Q. Which results in a decrease in 20 appetite if you curb the appetite? 21 A. If you want to put it that 22 way, that's correct, yes. 23 Q. You said curbing appetite, and 24 I said something else, but we're talking about Page 91 1 the same thing, aren't we? 2 A. I think so, yes. 3 Q. Since we're both from Texas, 4 we're still on the same -- 5 A. On the same wavelength, yes. 6 Q. Do you have an opinion, Doctor 7 Wheadon, with respect to whether or not Prozac 8 causes sexual dysfunction in some individuals? 9 A. Sexual dysfunction has been 10 noted in clinical trials in patients on Prozac. 11 Q. So would the answer to my 12 question be yes, whether it be in clinical trials 13 or in post-marketing experience, that's been 14 reported, hasn't it? 15 A. That's been reported, but I'm 16 not saying that Prozac clearly causes sexual 17 dysfunction. 18 Q. Well, do you believe Prozac 19 causes any adverse events? 20 A. The assumption of causality is 21 difficult, but in the case of certain adverse 22 events where the occurrence rate is at a certain 23 percentage, the assumption of causality is easier 24 than in the case of other adverse events. So as Page 92 1 we were discussing insomnia, the occurrence rate 2 is such that it's easier to make that assumption 3 of causality than it is in the case of adverse 4 events at a much smaller occurrence rate. 5 Q. Such as -- what would be 6 something that occurs at a smaller occurrence 7 rate? 8 A. To pick on the example you 9 just cited, sexual dysfunction is a bit more 10 difficult in assigning a causality for several 11 reasons, one being that sexual dysfunction can 12 often accompany depression. 13 Q. The same is true with insomnia 14 or weight loss or decreased appetite? 15 A. Right, that's correct. 16 Q. I drew those adverse events 17 purposely because you also see them in connection 18 with the disease itself. 19 A. That's correct, as also the 20 case of sexual dysfunction since the rates of 21 occurrence for sexual dysfunction is of the order 22 that a clear assignment of causality is a bit 23 more difficult. 24 Q. Where is the breaking point, Page 93 1 what rate do you have to have to have a clear 2 assignment of causality versus a not so clear 3 assignment of causality? 4 A. There is no particular 5 breaking point, it's a matter of looking at your 6 placebo rate versus the rate seen with your 7 active treatment. In some instances you look for 8 twice the placebo rate to come closer to an 9 assumption of causality than in other instances. 10 Q. So if it's twice the placebo 11 rate, it's more likely to be caused by the drug? 12 A. In some instances you look at 13 some -- rules may call for looking at at least 14 twice the placebo rate. 15 Q. What rules? 16 A. Rules of looking at adverse 17 events. And again, when I say rules I mean sort 18 of a general process of looking at adverse 19 events, assigning causality or not assigning 20 causality, or assigning possibility of causality. 21 It's a very complicated, very involved process 22 for looking at that sort of thing. 23 Q. You see that's one of the 24 issues involved in this lawsuit, these lawsuits, Page 94 1 is can you assign causality to Prozac to 2 individuals who become suicidal while on Prozac 3 or individuals who become violent aggressive 4 while on Prozac. You follow what I'm saying, 5 don't you? 6 A. Uh-huh. 7 Q. Do you have an opinion on 8 that, what do you have to have in order to 9 determine causality with respect to suicidality 10 and the use of Prozac? 11 A. I do not have an opinion about 12 what you have to have in order to determine 13 causality. 14 Q. Does that mean you don't have 15 an opinion then, Doctor Wheadon, concerning 16 whether or not Prozac can cause suicidality in an 17 individual? 18 A. I do have an opinion on that. 19 Q. All right. How can you have 20 an opinion on that when you don't know what it is 21 that would be required to assign causality? 22 A. When you ask a scientific 23 question, you don't ask expecting a certain 24 answer, you ask the question, you look at the Page 95 1 data, you then analyze the data at the end of the 2 day after having asked the question. So having 3 asked the question about Prozac and suicide, the 4 analyses have been done which you're very 5 familiar with, and the assumptions -- I mean the 6 conclusions based on those analyses, in my 7 opinion, indicate that Prozac is not associated 8 with suicide, suicidal behavior, suicidal 9 ideation, violent behavior or aggressive 10 behavior. 11 Q. Okay. What analysis are you 12 talking, what was done? 13 A. The analyses were carried out 14 on the controlled clinical trials, double-blind 15 controlled clinical trials, with Prozac, carried 16 out by Eli Lilly and Company both in the U.S. and 17 in Europe or outside the U.S. 18 Q. Well, are you talking about 19 that analysis made by Doctor Beasley in his 20 meta-analysis paper that was published in the New 21 England Journal of Medicine? 22 A. That's one of the analyses I'm 23 referring to. 24 Q. That's fine, I just want to Page 96 1 make sure I get all of the analyses that you're 2 referring to. Give me number two. 3 A. Analyses where carried out 4 looking at placebo controlled double-blind trials 5 in obsessive compulsive disorder. 6 Q. All right. 7 A. Analyses were carried out 8 looking at double-blind placebo controlled trials 9 in bulimia nervosa, which is an eating disorder. 10 Q. All right. 11 A. Analyses were carried out 12 looking at placebo controlled double-blind trials 13 in patients with obesity. 14 Q. All of these are clinical 15 trial -- is clinical trials data that you're 16 talking about? 17 A. That's correct. 18 Q. And all of these are 19 double-blind placebo controlled clinical trials? 20 A. That's correct. 21 Q. So the only analysis that 22 you're basing your opinion on is clinical trial 23 data that is double-blind placebo controlled in 24 depression studies and obsessive compulsive Page 97 1 disorders, bulimia and obesity, is that correct? 2 A. I think it also included 3 patients that were in the smoking cessation 4 trial. 5 Q. Anything else? 6 A. Those were the principal 7 analyses, yes. 8 Q. Of course you came out of 9 medical school with the opinion that individuals 10 who are depressed are more likely to commit 11 suicide than those who are not depressed, didn't 12 you? 13 A. When you say I came out of 14 medical school with that opinion -- 15 Q. Yes. 16 A. I learned in my medical 17 training that depressed individuals have as a 18 part of their symptoms, symptomatology, suicidal 19 thinking. A certain proportion of those go on to 20 act out on their suicidal thinking, they make 21 suicide attempts. Unfortunately a certain 22 portion of those that make suicide attempts are 23 successful, they end up in killing themselves. 24 So that is a part of the illness of depression, Page 98 1 yes. 2 Q. Okay. So would the answer to 3 my question be yes, when I came out of medical 4 school I was of the opinion that an individual 5 who is depressed is more likely to commit suicide 6 than an individual who is not depressed? 7 A. That's correct, yes. 8 Q. So you already had the answer 9 in part to your question before you began the 10 analysis of whether or not Prozac could cause 11 increased suicidality in depressed individuals, 12 didn't you? 13 A. No, I did not. 14 Q. You deny that you had a 15 preconceived idea concerning this issue before 16 you reviewed the data? 17 A. The question was put to the 18 data, if you want to look at it that way, and the 19 answer was generated. 20 Q. But the data -- the question 21 was put to the data after the data had already 22 been recorded, hadn't it? 23 A. The trials that were included 24 in the analyses had been completed and entered Page 99 1 into the data base, that's correct. 2 Q. And the clinical trials were 3 not designed and not intended to assess 4 suicidality, were they? 5 A. The clinical trials in 6 depression were intended to look at the response 7 of depressive symptoms to pharmacologic 8 treatment, in this case Prozac. 9 Q. That doesn't answer my 10 question, does it? The clinical -- I'll repeat 11 my question. The clinical trials were not 12 intended to assess the issue of suicidality in 13 depressed individuals, were they? 14 A. And my answer remains, the 15 clinical trials were intended to look at the 16 response of symptoms of depression to 17 pharmacologic treatment, in this case Prozac. 18 Q. How does that relate to the 19 question of suicidality? 20 A. One of the symptoms of 21 depression is suicidal ideation. One of the 22 things you look at in terms of determining 23 efficacy is how the symptoms of depression, one 24 of which is suicidal ideation, respond to Page 100 1 pharmacologic treatment. So to say that the 2 studies were not intended to test that hypothesis 3 is not completely correct, and I cannot answer 4 yes to that. 5 (PLAINTIFFS' EXHIBIT NO. 1 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 (DISCUSSION OFF THE RECORD.) 9 Q. Why don't you review that 10 document and I'm going to ask you some questions 11 about it, Doctor Wheadon. 12 (WITNESS REVIEWS DOCUMENT.) 13 Q. Doctor Wheadon, Exhibit Number 14 1 is a document that we talked with Doctor 15 Heiligenstein and Doctor Beasley about. Do you 16 recall Exhibit 1? 17 A. I do not recall Exhibit 1 in 18 particular other than you're showing it to me at 19 this point. 20 Q. Well, you are an addressee of 21 the exhibit, are you not? 22 A. That's correct? 23 Q. And you were part of a team 24 consisting of Doctors Zerbe, Heiligenstein, Page 101 1 Beasley and Gordon who assisted Doctor Masica in 2 issues presented by Prozac, correct? 3 A. That's correct. 4 Q. Specifically you all were 5 helping Doctor Leigh Thompson in connection with 6 discussing the issue of Prozac in suicide and 7 violent behavior, were you not? 8 A. That's correct. 9 Q. And do you recall that Doctor 10 Leigh Thompson was making a report to the board 11 of directors of Eli Lilly and Company and Mister 12 Wood, the chairman of the board of directors, in 13 connection with this issue? 14 A. I don't recall that the 15 presentation referred to in the document you 16 handed me was for the board of directors. 17 Q. Well, you see on page one 18 where it says the verbatims are just for Mister 19 Wood, do you not? 20 A. I see that comment, yes. 21 Q. And he's the chairman of the 22 board of directors, or was the chairman of the 23 board of directors of Eli Lilly and Company at 24 the time, was he not? Page 102 1 A. Mister Wood at the time of 2 this document was also chief executive officer 3 and president. 4 Q. My question was he was 5 chairman of the board of directors, was he not? 6 A. And also chief executive 7 officer and president. 8 Q. I didn't ask you whether he 9 was chief executive officer and president, my 10 question was was he at the time chairman of the 11 board of directors -- 12 A. He was. 13 Q. -- simple as that? 14 A. Among several other 15 responsibilities, he was chairman of the board of 16 directors. 17 Q. I'm not intending to trick 18 you. If I needed to know whether he was 19 president or chief executive officer, I would 20 have asked you that. 21 A. You're asking me if this was 22 in preparation for a board of directors' meeting, 23 and I do not recall that nor is that mentioned in 24 this document. Page 103 1 Q. Well, we have other documents, 2 and Doctor Heiligenstein and Doctor Beasley and 3 Doctor Zerbe have all said this was in 4 preparation for a meeting for the board of 5 directors, okay? 6 A. I don't recall that. 7 Q. All right. Do you recall 8 looking at this data that is mentioned in Exhibit 9 1? 10 A. When you say looking at this 11 data, I'm not sure what you mean. 12 Q. The verbatims -- the verbatims 13 and this information that Doctor Thompson is 14 going to talk with Mister Wood about. 15 A. I do not recall the specific 16 data referred to in this document. 17 Q. Do you see on page two, Doctor 18 Wheadon, where the mention is made of page five? 19 A. You're referring to the item 20 on the second page under page five? 21 Q. Yes. 22 A. Okay. 23 Q. This document is authored by 24 Doctor Heiligenstein, is it not? Page 104 1 A. It's signed, computer signed, 2 by John Heiligenstein, that's correct. 3 A. On page one, it says Charles, 4 David and I have reviewed your presentation and 5 offer the following thoughts slash comments, does 6 it not? 7 A. That's correct, it does say 8 that. 9 Q. That David there is referring 10 to you, isn't it? 11 A. Yes, that is correct. 12 Q. There are not any other Davids 13 that he could be talking about that you know of, 14 is there? 15 A. There was David Goldstein 16 present on the staff as well. 17 Q. But David Goldstein is not 18 mentioned. 19 A. That's correct. So the 20 assumption is that the David he's referring to is 21 indeed me. 22 Q. Do you see on page two under 23 page five under suicidal thinking in clinical 24 trials, you may want to note that trials were not Page 105 1 intended to address issue of suicidality. Also 2 in paragraph two, patients were excluded who were 3 serious suicidal risks, correct? 4 A. That is written in this 5 document, yes. 6 Q. Did I read that correctly? 7 A. That is correct. 8 Q. Do you disagree with Doctor 9 Heiligenstein that the clinical trials were not 10 intended to address the issue of suicidality? 11 A. That is a very vague 12 statement. 13 Q. Okay. Well, I didn't ask you 14 whether it was vague or not, I asked you whether 15 or not you disagreed with Doctor Heiligenstein's 16 statement that trials were not intended to 17 address the issue of suicidality? 18 A. I cannot agree nor disagree 19 with Doctor Heiligenstein's statement as written 20 here because it is a very vague statement. 21 Q. In what respect is it vague, 22 Doctor Wheadon? 23 A. Suicidality is a grossly 24 general term, so I'm not at liberty to assume Page 106 1 what Doctor Heiligenstein in September of 1990 2 meant by the term "issue of suicidality." 3 Q. Do you recall writing anything 4 to either Doctor Leigh Thompson or Doctor 5 Heiligenstein saying that suicidality as used on 6 page two of this report is a grossly vague term 7 that you couldn't agree or disagree with? 8 A. I don't recall writing that, 9 no. 10 Q. Do you recall thinking that -- 11 A. Yes. 12 Q. -- when you read it? 13 A. I recall in several 14 discussions about suicidality making the 15 statement that that is a grossly general term. 16 Q. All right. Did you point 17 anything out in connection with Exhibit 1? 18 A. I do not recall pointing 19 anything out on the issue of suicidality as a 20 grossly general term as discussed in Exhibit 1. 21 Q. In what way are you of the 22 opinion that the term suicidality is too general? 23 I assume when you say grossly general, it's too 24 general. Page 107 1 A. The term suicidality can 2 encompass such things as suicidal ideation, 3 suicide attempts, and completed suicides. 4 Q. I doubt if anybody would 5 disagree with you on that, I doubt if Doctor 6 Heiligenstein, Doctor Thompson or Doctor Zerbe 7 would disagree with that. Do you have -- I guess 8 my point is, do you criticize Doctor 9 Heiligenstein for using the term suicidality on 10 page two here? 11 A. I criticize Doctor 12 Heiligenstein in terms of the statements that 13 precedes the term suicidality. 14 Q. Okay. What is that? 15 A. You may want to note that 16 trials were not intended to address issue of 17 suicidality. 18 Q. All right. So what do you 19 disagree with about that? 20 A. As I stated earlier, suicidal 21 ideation is a core symptom of depression, is 22 assessed in clinical trials of depression of 23 pharmacologic agents as an effect of treatment. 24 Q. How? Page 108 1 A. In several ways. One, in 2 assessment of patients in terms of their core 3 symptoms, one of the standard questions is have 4 you thought about suicide, have you thought about 5 harming yourself. That's a standard assessment 6 in dealing with depressed patients. Another way 7 is in the Hamilton rating scale, standard scale 8 for evaluating the level of symptomatology in 9 depression, one of the questions asks 10 specifically about suicide. 11 Q. Item three? 12 A. Item three, exactly. 13 Q. When you say there's a 14 standard assessment made in analyzing depression 15 concerning suicidality, what is your 16 understanding that that's asking of every patient 17 in every clinical trial? 18 A. My understanding is based on 19 my training, my medical training. One of the 20 core things you ask about in dealing with 21 depressed patients is how they're feeling, their 22 level of hopelessness, their level of wanting to 23 hurt themself or not. That's a core question, 24 very similar to asking a patient with pneumonia, Page 109 1 have you felt hot, do you have a fever. Very 2 common questions asked in treating depressed 3 patients. 4 Q. But suicidality is not a core 5 symptom of depression, such as is insomnia, 6 weight loss, decreased libido, and things of that 7 nature. 8 A. If you remember or go back and 9 review the nine symptoms as spelled by DSM-3R, 10 suicidal -- hopelessness, thoughts of suicide, is 11 one of the symptoms listed in DSM-3R. 12 Q. It's just hopelessness, isn't 13 it? 14 A. No, there's also thoughts of 15 suicide or thoughts of death mentioned in DSM-3R. 16 Q. All right. So is it your 17 opinion that each investigator goes over each of 18 the nine core symptoms and includes hopelessness, 19 thoughts of suicide, in making an evaluation of 20 each and every patient that was ever in the 21 clinical trials? 22 A. I cannot say that each 23 investigator asks each and every patient all nine 24 symptoms in DSM-3R, I cannot say that. Page 110 1 Q. So since you don't know that, 2 you can't make the assertion that everyone who is 3 in the clinical trials had this assessment done, 4 can you, Doctor? 5 A. I certainly cannot assure that 6 every investigator asks every patient each of the 7 nine symptoms listed in DSM-3R. 8 Q. Let's go a little further, 9 though. Most of the protocols had exclusion or 10 inclusion criteria on suicidality, did they not? 11 A. The protocols -- most of the 12 protocols had as an exclusion criteria serious 13 suicidal risk. 14 Q. So you would expect the 15 physician, the investigator, to make an 16 assessment with respect to whether or not a 17 patient was a serious suicidal risk, wouldn't 18 you? 19 A. At the time of inclusion? 20 Q. Yes. 21 A. That's correct. 22 Q. But whether a patient is a 23 serious suicidal risk and whether or not a 24 patient has ever had any suicidality feelings is Page 111 1 two different questions, isn't it? 2 A. A patient being a serious 3 suicidal risk at time of interview or time of 4 evaluation is different from a patient having a 5 history of thoughts of suicide or suicidal 6 behavior in the past, yes, that is correct. 7 Q. In other words some of the 8 patients who participated in the Prozac 9 depression clinical trials had expressed thoughts 10 of suicide in the past. 11 A. That's correct. 12 Q. But were not excluded because 13 they weren't at the time serious suicidal risk as 14 mentioned by the protocol? 15 A. That's correct. 16 Q. Now item three on the Hamilton 17 depression scale is only one item of many, is it 18 not? 19 A. It's one item, in most 20 versions, of the Hamilton twenty-one. 21 Q. So it's one-twenty-first of 22 the assessment that's made of the patient's 23 depression? 24 A. Within the context of the Page 112 1 twenty-one item Hamilton scale, that's correct. 2 Q. Certainly there are many or 3 there are more sophisticated ways to analyze 4 suicidality in an individual than the Hamilton 5 depression scale, aren't there, Doctor Wheadon? 6 A. To answer the first part of 7 your question, there are not many sophisticated 8 ways of analyzing suicidality in a depressed 9 patient, no. 10 Q. But there are several? 11 A. There are other ways of 12 looking at suicidality in a depressed patient, 13 that is correct. 14 Q. There are other well-known 15 inventories that are more sensitive in examining 16 the issue of suicidality, aren't there? 17 A. I cannot say that there are 18 other well-known inventories that are more 19 sensitive in evaluating suicidality. 20 Q. What term would you use, 21 Doctor Wheadon? 22 A. I would say that there are 23 other inventories that discuss, in terms of a 24 greater number of questions, the issue of Page 113 1 suicidal thoughts or behavior. 2 Q. Don't you think they would be 3 more sensitive in determining level of 4 suicidality than that simple one question that 5 has four parts to it on item three of the 6 Hamilton Depression Scale? 7 A. That is not necessarily true. 8 Q. You don't agree that they're 9 more sensitive, for instance the suicidal 10 inventory scale is more sophisticated and 11 sensitive in picking up suicidality and assessing 12 suicidality than item three on the Hamilton 13 Depression Scale? 14 A. A validation effort looking at 15 the Hamilton versus the Beck has not been carried 16 out to my knowledge, so to make a statement that 17 it's more sensitive, vis-a-vis the Hamilton, I 18 cannot agree with. 19 Q. Is it better in any way in 20 addressing the issue of suicidality? 21 A. What do you mean by better? 22 Q. Or more diagnostic. 23 A. One question can be diagnostic 24 of suicidality, meaning ideation, acts or Page 114 1 behavior. One question can very easily ferret 2 out a patient's intent in terms of how they're 3 feeling and what they may do with those feelings. 4 Q. Doctor Wheadon, if you were 5 concerned about the suicidality or whether or not 6 one of your loved ones was experiencing 7 suicidality, would you rather have them 8 administered the Beck Suicide Inventory or item 9 three only of the Hamilton Depression Scale? 10 A. I'm lost by that question, 11 would you repeat it? 12 MR. SMITH: Would you read it back? 13 (THE COURT REPORTER READ BACK THE 14 REQUESTED TESTIMONY.) 15 A. To be quite honest with you, 16 in answer to your question, I would prefer that a 17 loved one of mine who might be experiencing 18 suicidal ideas or behavior be asked one simple 19 question. 20 Q. You know what I'm going to ask 21 you, don't you? What is that question? 22 A. Do you have thoughts of 23 suicide; if you do, do you have intent of acting 24 out on those thoughts. Page 115 1 Q. That's two questions. 2 A. That's, comma, semi-colon, 3 whichever way you want to look at it. 4 Q. Do you have thoughts of 5 suicide, and if you do, do you have intent to act 6 on that? 7 A. Exactly. 8 Q. And you think that's the most 9 important question to be asked a patient -- 10 A. Yes, in my opinion. 11 Q. -- with this problem? 12 A. In my opinion, that is the 13 most important question to be asked of a suicidal 14 patient or potentially suicidal patient. 15 Q. Have you ever asked a patient 16 that? 17 A. Yes. 18 Q. Would you make the 19 determination of whether or not to hospitalize a 20 patient to protect that patient based solely on 21 the response to that one question? 22 A. Yes. 23 Q. You don't think that there's 24 any other questions that need to be asked to a Page 116 1 patient that might pose a risk of suicide? 2 A. Your question to me was if 3 there was one question, what is it. That is the 4 one question. Yes, there are other questions to 5 be asked. Your question to me was if there's one 6 question, important question, what is it. 7 Q. I guess we got on this through 8 the discussion of the Ham-D, item three, which is 9 one question, correct, with four different ways 10 to answer it, and the Beck Suicide Inventory, 11 correct, which is how many questions on the Beck 12 Suicide Inventory? 13 A. I don't recall how many 14 questions are on the Beck. 15 Q. Have you ever seen it? 16 A. Yes, I have. 17 Q. Have you ever administered it? 18 A. I have not utilized the Beck 19 Suicide Inventory, no. 20 Q. Do you not like it? 21 A. It's not a matter of liking it 22 or not, I have not utilized it. 23 Q. If you were going to do a 24 clinical trial on depressed patients, and you Page 117 1 were concerned about the issue of whether or not 2 the drug that was the subject of the clinical 3 trial could cause depression, would you use the 4 Beck Suicide Inventory? 5 A. Not necessarily. 6 Q. Why? 7 A. The Beck Suicide Inventory was 8 not designed nor validated to test that question. 9 Q. What was it designed or 10 validated for? 11 A. The Beck Suicide Inventory was 12 designed to look at suicide in depressed 13 patients, the level of suicide, the thoughts of 14 suicide, intentions or lack thereof, it was not 15 designed to test whether or not a drug was 16 causing suicidality. 17 Q. Well, your one question 18 wouldn't address that either, would it? 19 A. The item three of the 20 Hamilton, as well, was not concluded to test the 21 question of whether or not a drug was causing 22 suicidality in a patient. 23 Q. So then what's wrong with 24 Doctor Heiligenstein's statement that says the Page 118 1 trials were not intended to address the issue of 2 suicidality? 3 A. Doctor Heiligenstein's 4 statement says nothing about drugs causing 5 suicidality, Doctor Heiligenstein's general 6 statement says the trials were not intended to 7 assess of issue of suicidality. Again, a general 8 term. One of the things included in suicidality 9 is suicidal ideation, a core symptom of 10 depression. One of the questions on the 11 Hamilton, a scale intended to assess the symptoms 12 of depression, in terms of the level of severity 13 of those symptoms, deals with suicidal ideation. 14 Q. Okay. So you disagree with 15 Doctor Heiligenstein? 16 A. In terms of that general 17 statement, yes, I do. Could we have a break? 18 (A SHORT RECESS WAS TAKEN.) 19 Q. Do I take it, Doctor Wheadon, 20 that it's your opinion that item three of the 21 Ham-D scale is sufficient to measure suicidal 22 ideation in patients? 23 A. Item three of the Ham-D scale 24 is intended assess that portion of the Page 119 1 depression, that being suicidal thinking, in 2 depressed patients. 3 Q. My question was do you think 4 it's sufficient? 5 A. Yes, I think it is sufficient 6 for measuring changes in suicidal thinking. 7 Q. Do you think it's sufficient 8 to use to draw a conclusion concerning whether or 9 not Prozac causes suicidality, that is going back 10 and analyzing item three? 11 A. I think that item three is 12 sufficient to test the hypothesis of whether or 13 not there are changes in suicidal thinking based 14 upon the initiation of drug treatment. 15 Q. And the initiation of Prozac 16 drug treatment? 17 A. In particular, yes. 18 Q. Do you feel that the issue of 19 whether or not Prozac causes suicidality is 20 sufficiently assessed in the meta-analysis done 21 by Doctor Beasley? 22 A. I feel that if there was an 23 association between Prozac and the induction of 24 suicidal thinking or behavior, the analyses Page 120 1 carried out in the series of analyses we've 2 discussed, including the one in Doctor Beasley's 3 paper, should have indicated that, and it did 4 not. 5 (PLAINTIFFS' EXHIBIT NO. 2 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Exhibit 2 is a document that 9 you authored, is it not? 10 A. Yes, that's correct. 11 Q. And it's a report of a trip 12 you made to Europe, is it not? 13 A. That's correct. 14 Q. And you specifically made a 15 trip while you were in Lilly's employ to visit 16 with European consultants on the potential 17 relationship between fluoxetine treatment and 18 suicidal ideation and/or behavior, did you not? 19 A. That's correct. 20 Q. And you made that trip August 21 8th through the 15th of 1990, didn't you? 22 A. That's correct. 23 Q. And you reported with -- or 24 you met with seven psychiatrists, correct? Page 121 1 A. That's correct. 2 Q. Did anybody go with you on 3 this trip, any of your co-physicians at Lilly or 4 did you go alone? 5 A. I was accompanied in the 6 individual countries by physicians from those 7 countries. 8 Q. But you didn't take, say, like 9 Doctor Heiligenstein or anybody else with you? 10 A. No, no one from Indianapolis 11 accompanied me on that trip. 12 Q. In the fourth paragraph of 13 page one, where you were talking about a summary 14 of the discussions, you say the consultants were 15 impressed and assured by the data presented in 16 the suicidality report. You go on to report, 17 though, that, quote, they noted, however, that 18 clinical trial data of this sort is limited, 19 particularly the analysis of the Hamilton 20 psychiatric rating scale for depression, Ham-D, 21 item three, suicidality data, correct? 22 A. That is written in the report, 23 that's correct. 24 Q. Do I take it by that that Page 122 1 these experts, the European consultants are 2 differing with you in their confidence in the 3 Ham-D, item three, suicidality data? 4 A. I don't agree with that, no. 5 Q. Well, you're reporting that 6 they say this data is limited, are you not? 7 A. That's correct. 8 Q. I'm assuming you're reporting 9 what they reported to you? 10 A. That's correct. 11 Q. You also go on on the last 12 page of that exhibit -- or on the second page, 13 the last page of text of that exhibit, to say, 14 quote, each of the consultants felt that the most 15 definitive assessment of a potential relationship 16 between fluoxetine treatment and suicidal 17 ideation or behavior would be some sort of 18 prospective study, end quote. 19 A. That's written in the report, 20 that's correct. 21 Q. Was that accurate when it was 22 written? 23 A. That the consultant made that 24 recommendation, yes, that's correct. Page 123 1 Q. And was it accurate that the 2 consultants reported to you that the clinical 3 trial data using item three, the suicidality 4 data, was limited? 5 A. That's what is written in the 6 report. 7 Q. Did you express your 8 disagreement with the European consultants 9 concerning the accuracy and the reliability of 10 item three on the Hamilton Depression Scale? 11 A. I don't see where the 12 consultants and I are in disagreement. 13 Q. I thought you said that you 14 thought that item three was sufficient to analyze 15 the issue of suicidality? 16 A. I made the statement that item 17 three is sufficient for looking at changes in 18 suicidal ideation in depressed patients. 19 Q. Well, the experts in Europe 20 said that the clinical trial data of this sort is 21 limited, didn't they? 22 A. I don't see where there's a 23 difference in opinion there. 24 Q. Okay. Now are you saying that Page 124 1 the item three suicidality portion of the 2 Hamilton Depression Scale is limited in some 3 respects? 4 A. As I pointed out, item three 5 of the Hamilton Depression Scale looks at 6 suicidal ideation. 7 Q. Okay. 8 A. As we discussed earlier, 9 suicidality as a general vague term encompasses 10 other things in addition to suicidal ideation. 11 So in this respect, item three is limited in that 12 it looks at suicidal ideation, changes in 13 suicidal ideation, if you will. So I don't see 14 where there's a difference in opinion. 15 Q. All right. Do you agree that 16 the best way or that the most definitive 17 assessment of this issue of the potential 18 relationship between fluoxetine treatment and 19 suicidal ideation and/or behavior would be an 20 assessment of the potential relationship by some 21 sort of prospective study? 22 A. I agree that the most 23 definitive assessment of the question is a 24 prospective study. Page 125 1 Q. That was never done as far as 2 you know, was it? 3 A. At the time -- during the time 4 that I was at Eli Lilly, a prospective study had 5 not been carried out, that is correct. 6 Q. And to your knowledge it still 7 has not been done, has it? 8 A. I'm not aware of it. Again, 9 I'm no longer privy to those discussions, I have 10 no idea. 11 Q. You've not seen any reports in 12 the scientific literature concerning a 13 prospective study that's been done. 14 A. I have not seen reports in the 15 scientific literature concerning a prospective 16 study carried out by Eli Lilly, no. 17 Q. Are you aware of a prospective 18 study done by anyone? 19 A. I cannot recall a prospective 20 study done by anyone, no. 21 Q. And, Doctor, I'm not 22 interested in infringing on any trade secrets of 23 SmithKline Beecham, so be careful not to give me 24 any in answering this question, but does your Page 126 1 work at SmithKline Beecham involve 2 antidepressants now? 3 MR. COLEMAN: You can answer that 4 question yes or no. 5 A. Yes. 6 Q. Does it involve specific 7 serotonin reuptake inhibitors? 8 A. Yes. 9 Q. Does SmithKline Beecham 10 currently market a specific serotonin reuptake 11 inhibitor for depression? 12 A. Yes. 13 Q. What is the name of that 14 product? 15 A. The name of that drug is 16 Paxil, the generic name is paroxetine. 17 Q. Have there been any studies 18 comparing paroxetine and fluoxetine 19 hydrochloride, Prozac? 20 MR. COLEMAN: I'm going to instruct 21 you not to answer that question, it's irrelevant 22 to this case and it infringes on his involvement 23 and work at SmithKline. 24 Q. Have there been any published Page 127 1 studies comparing Paxil to Prozac? 2 MR. COLEMAN: You can answer. 3 A. There have been published 4 studies comparing Paxil, fluoxetine -- and 5 fluoxetine. 6 Q. And that's Paxil and Prozac, 7 right? 8 A. In the United States? 9 Q. Yes. 10 A. In the United States it's 11 Paxil and Prozac, yes. 12 Q. And have any of those studies 13 examined differences in suicidality between those 14 products? 15 A. No, they have not. 16 Q. Has SmithKline Beecham engaged 17 in a prospective study to determine whether or 18 not there's a relationship between Paxil and 19 suicidal ideation and behavior? 20 MR. COLEMAN: I instruct you not to 21 answer that question. 22 MS. ZETTLER: Certify those questions 23 that have been instructed. 24 (QUESTIONS CERTIFIED.) Page 128 1 Q. Have there been any studies 2 published examining prospective studies 3 concerning Paxil and suicidal ideation and 4 behavior? 5 MR. COLEMAN: You can answer that 6 question. 7 A. No, there have not. 8 Q. Are you familiar with Doctor 9 David Dunner's study which was a meta-analysis on 10 paroxetine that's been published? 11 A. Yes, I am familiar with Doctor 12 Dunner's study. 13 Q. And has it been published? 14 A. That has been published, yes. 15 Q. Was that a prospective study? 16 A. That was not a prospective 17 study. 18 Q. All right. Did it measure 19 suicidality or address the issue of suicidality? 20 A. If I remember correctly, it 21 did address the issue of suicidal changes and 22 suicidal thinking while on pharmacologic 23 treatment. 24 Q. And did it compare Paxil and Page 129 1 Prozac? 2 A. It did not. 3 Q. What did it compare? 4 A. Paxil or paroxetine was 5 compared to placebo and to active treatments, 6 primarily tricyclic antidepressants. 7 Q. But fluoxetine was not a 8 comparitor arm of that study? 9 A. No, it was not. 10 Q. When you returned to the 11 United States, did you discuss the opinion of the 12 consultants that the most definitive assessments 13 of the potential relationship between fluoxetine 14 treatment and suicidal ideation would be some 15 sort of prospective study with individuals at 16 Lilly? 17 A. Yes, I did. 18 Q. With whom did you discuss 19 that? 20 A. Doctor Thompson, Doctor Zerbe, 21 Doctor Heiligenstein, Doctor Beasley, Doctor 22 Masica, the entire group was aware of the opinion 23 expressed by the European consultants. 24 Q. Did you discuss doing a Page 130 1 prospective study since it had been something 2 that was mentioned by the European consultants? 3 A. The issue of doing a 4 prospective study was discussed. 5 Q. And tell me about those 6 discussions. 7 A. As pointed out by the European 8 consultants and other consultants in the U.S., 9 and as agreed to in discussions with Eli Lilly, a 10 prospective study of this sort would be 11 extraordinarily difficult to do. 12 Q. Why? 13 A. Because in the issue of 14 looking for pharmacologic treatment causing 15 changes in suicidal thinking or behavior, the 16 rate of occurrence of such seems to be based on 17 the retrospective analyses so low that you would 18 need to study thousands of patients to have 19 enough power to detect a difference if one 20 exists. 21 Q. Well, was a decision made that 22 this was just such a difficult question you would 23 have to study so many people that it just 24 shouldn't be done? Page 131 1 A. That was not a decision that 2 was made. At the time I left Eli Lilly, 3 discussions were ongoing about what, if any, 4 prospective study could be carried out. 5 Q. But the reason that a 6 prospective study had not been carried out by the 7 time you left was because of these difficulties 8 that you mentioned? 9 A. Because of that difficulty in 10 addition to others, yes. 11 Q. What others? 12 A. Well, you also have the issue 13 of ethical considerations. If you're posing a 14 question of whether or not treatment promotes 15 suicidal behavior, then the ethics of doing a 16 study to test that question get a bit difficult, 17 not impossible but difficult. 18 Q. Well, in connection with 19 ethics, I mean there are ten million people 20 taking Prozac already, so there are a lot of 21 people being exposed to it. Wouldn't it be more 22 ethical to examine the issue in depth than to 23 leave ten million people at risk? 24 A. Well, number one, you're Page 132 1 assuming that patients on treatment are at risk, 2 and that has not been established. 3 Q. The consultants are suggesting 4 that that would be the most definitive way -- 5 that would be the best way to get the most 6 definitive answer, aren't they? 7 A. If a decision was made to get 8 a definitive answer in a prospective fashion, 9 that would be the way to do it, yes. 10 Q. Didn't these physicians at 11 Lilly want to get the most definitive answer? 12 A. Physicians at Lilly clearly 13 felt that the analysis that had been carried out 14 had not given any indication that there was a 15 causal relationship between pharmacologic 16 treatment, Prozac in particular, but other 17 pharmacologic treatment as well, and changes in 18 suicidal thinking or behavior. 19 Q. But that was six or seven 20 physicians' opinion there, wasn't it? 21 A. In terms of physicians at 22 Lilly, there were six or seven or more, yes. 23 There were also outside consultants that agreed 24 with that opinion. Page 133 1 Q. Well, the outside consultants, 2 in my judgment, are saying they felt the most 3 definitive assessment of the potential 4 relationship between fluoxetine treatment and 5 suicidal ideation would be some sort of 6 prospective study, aren't they? 7 A. I would also say the 8 consultants were impressed and assured by the 9 data presented in the suicidality report. 10 Q. Even though you say that, you 11 also say that they are saying that the most 12 definitive assessment would be a prospective 13 study. 14 A. That's correct. 15 Q. I'm assuming that they're 16 recommending that some prospective study be done, 17 aren't they? 18 A. That is not necessarily the 19 case. 20 Q. You think my assumption is 21 wrong? 22 A. The statement was, as you've 23 read, that the most definitive assessment would 24 be some sort of prospective study. Page 134 1 Q. Doctor Wheadon, let me ask you 2 directly, did any of those experts say the best 3 way to get to the answer to the question posed is 4 to do a prospective study? 5 A. The consultants made the 6 statement that I've outlined in the report, the 7 most definitive way of answering the question is 8 a prospective study. 9 Q. So weren't they recommending 10 that a prospective study be done? 11 A. No, they were not. 12 Q. Did anybody ever recommend 13 while you were at Lilly that a prospective study 14 be done? 15 A. Opinions were expressed that 16 the most definitive way to answer the question 17 scientifically is a prospective study. 18 Q. But that wasn't done while you 19 were there. 20 A. It was not carried out while I 21 was at Lilly. 22 Q. And the reason it wasn't done 23 was because it would be difficult, it would 24 involve some ethical considerations, and you Page 135 1 would have to expose a lot of people to the drug. 2 A. You would have to study 3 thousands of people, not expose, study, thousands 4 of people. 5 Q. But there are ten million 6 people taking the drug, aren't there, Doctor 7 Wheadon, or that's what's reported in the lay 8 press? 9 A. I'm not sure what the actual 10 number of people taking Prozac at this time is. 11 Q. It's still the most widely 12 prescribed antidepressant on the market, isn't 13 it? 14 A. As far as I can recollect, 15 Prozac is a very widely prescribed 16 antidepressant. 17 Q. The most widely prescribed, 18 isn't it? 19 A. I have not seen recent 20 figures, so I cannot agree with that statement. 21 Q. At the time you left Lilly in 22 1992, it was, wasn't it? 23 A. At the time I left Lilly, in 24 the overall prescription market Prozac was not Page 136 1 the most widely prescribed antidepressant. 2 Q. What was? 3 A. If I remember correctly, 4 either the tricyclics as a group or one of the 5 tricyclics actually may have been more widely 6 prescribed than Prozac at the time I left Lilly. 7 Q. Which one? 8 A. I cannot recall exactly which 9 one. 10 Q. Are you saying that at the 11 time you left Lilly, there was more people on 12 some other antidepressant than there were on 13 Prozac? 14 A. If I recall correctly, yes. 15 Q. And you think this was a 16 tricyclic? 17 A. Yes. 18 Q. But you don't know which one 19 it was? 20 A. I cannot recall exactly which 21 one. 22 Q. Ten million people is a large 23 number of people taking one particular medicine, 24 is it not? Page 137 1 A. If you consider the number of 2 people taking aspirin, there are more than ten 3 million people taking aspirin. 4 Q. I didn't ask you to consider 5 the number of people taking aspirin, I asked you 6 if ten million people is a large number of people 7 to be taking a medicine, isn't it? 8 A. I don't agree that ten million 9 people is an overwhelmingly large number of 10 people to be taking a medicine, no. 11 Q. What would be an 12 overwhelmingly large number of people taking a 13 particular medicine, Doctor Wheadon? 14 A. If every individual in the 15 world was taking one medication, that would be an 16 overwhelmingly large number of people taking a 17 medication. 18 Q. I'm not suggesting that it's 19 inappropriate, I'm just suggesting that ten 20 million people is a large amount of people to be 21 taking a particular medication. Do you disagree 22 with that? 23 A. Ten million people is a large 24 number of people, yes. Page 138 1 Q. All right. Now, back to the 2 question. Did anybody recommend while you were 3 at Lilly that there be a prospective study done 4 on the issue of Prozac and suicidality? 5 A. A recommendation from the 6 consultants that I encountered was that to 7 definitively answer the question, a prospective 8 study would be the most definitive way of doing 9 so. 10 Q. Were they suggesting that this 11 be done? 12 A. No, not necessarily. 13 Q. Did the Food and Drug 14 Administration ever suggest that a prospective 15 study be done? 16 A. The Food and Drug 17 Administration, in the form of the psychopharm 18 division and neuropharm division, as well, lists 19 among the various ways of answering the question 20 would be a prospective study. 21 Q. Did they ever suggest that 22 Lilly perform a prospective study? 23 A. A recommendation was made that 24 we consider the possibility of doing a Page 139 1 prospective study to answer the question. 2 (PLAINTIFFS' EXHIBIT NO. 3 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. Doctor Wheadon, Exhibit 3 is a 6 memorandum dated July 18, 1990 from Doctor Leigh 7 Thompson concerning a 6:15 a.m. telephone 8 conversation between Doctor Leigh Thompson and 9 Doctor Paul Leber and Doctor Tom Laughren of the 10 United States Food and Drug Administration, is it 11 not? 12 A. Doctor Leber and Doctor 13 Laughren are employees of the FDA, yes. 14 Q. The call, according to the 15 memo, was about suicide, correct? 16 A. That's correct. 17 Q. And that memo reflects that 18 Paul suggested several designs, correct? 19 A. The memo says that Paul, 20 meaning Doctor Leber, suggested several designs, 21 yes. 22 Q. And Doctor Leber at that time 23 was a high ranking official in the 24 neuropsychopharmacology division of the Food and Page 140 1 Drug Administration? 2 A. That's correct. 3 Q. And item three, which he 4 suggested was, quote, best would be a larger 5 prospective study designed with the help of 6 Teicher to detect his phenomena. Paul said he 7 wasn't commanding any of these particular 8 designs, but wanted to express strongly his 9 feelings that some data are needed, end quote, 10 correct? 11 A. That's what the memo reads, 12 yes. 13 Q. You're a recipient of this 14 memo, are you not? 15 A. I'm not a direct recipient of 16 the memo, no, I'm not. 17 Q. Well, you're an indirect on 18 the top of the page. It says to, and then you're 19 listed under the to, are you not? 20 A. It was forwarded to me, yes, 21 but I was not a direct recipient. 22 Q. You received it, didn't you? 23 A. I got a copy of this memo, 24 that's correct. Page 141 1 Q. And it was intended that you 2 have this information, wasn't it? 3 A. By the person who forwarded 4 the information to me, yes. 5 Q. Apparently -- who forwarded it 6 to you? 7 A. My assumption is that it's Dan 8 Masica, but that's not clear based on what you've 9 given me. 10 Q. He's your supervisor, correct? 11 A. Again, it's not clear. Based 12 on what you've given me, that's my assumption, 13 that it came from Dan Masica. 14 Q. Dan Masica, it is clear, was 15 your immediate supervisor at the time, wasn't he? 16 A. That's correct. 17 Q. And I would assume that you 18 felt at the time that if Doctor Masica was the 19 one that forwarded this to you, he wanted you to 20 have this information? 21 A. My point is, it may have been 22 sent by Doctor Masica, it may have been sent by 23 Doctor Zerbe. It's not clear, based on what 24 you've handed me, who the person is that Page 142 1 forwarded the memo to me. 2 Q. Whoever handed it to you, it 3 was handed to you, forwarded to you, so that you 4 could have this information, wasn't it? 5 A. The statement is for your 6 information to keep you all up to date. 7 Q. And was it your habit, sir, to 8 read information forwarded to you either directly 9 or indirectly? 10 A. Yes. 11 Q. And did you feel that this is 12 something that you needed to have as a clinical 13 research physician with Eli Lilly and Company? 14 A. Certainly this was something 15 that we working on the issue of Prozac and 16 suicide needed to be aware of, I would agree with 17 that. 18 Q. Would you agree with me that 19 Doctor Leber is suggesting that best would be a 20 larger blind prospective study? 21 A. Doctor Leber is offering the 22 opinion, as others have, that the most definitive 23 test of the hypothesis is a prospective study. 24 Q. He doesn't say most Page 143 1 definitive, he uses another term, doesn't he? 2 A. He uses the term -- Leigh, I'm 3 sorry, not Doctor Leber. Leigh, in his 4 recounting of the discussion, used the term best, 5 I don't know what term Doctor Leber used. 6 Q. Best is the term that's 7 written here by Doctor Thompson? 8 A. That is correct. 9 Q. Did you have any instances in 10 any of the times that you worked with Doctor 11 Leigh Thompson where he did not accurately report 12 subjects? 13 A. What do you mean by accurately 14 report? 15 Q. Correctly relay the 16 information that was given to him. 17 A. Any relaying of information is 18 subject to one's own understanding and hearing of 19 the information. So Doctor Thompson, in his 20 memos to various people, may have gotten, in some 21 instances, the information that was relayed to 22 him confused. 23 Q. Do you know of any such 24 instance, Doctor Wheadon? Page 144 1 A. I cannot recall an exact 2 instance to mind, but I can tell you that Doctor 3 Thompson, in his relaying of information to other 4 individuals which he has received, he sometimes 5 had been known to get information confused. 6 Q. Did you ever express to him 7 that criticism, Doctor Wheadon? 8 A. Doctor Thompson, as any human 9 being, anyone around the table, has the 10 possibility to get information confused when they 11 have received loads of information. 12 Q. Do you have any reason to 13 believe that Doctor Leigh Thompson is misquoting 14 or missupplying the information reported to him 15 by Doctor Paul Leber that, quote, best would be a 16 larger blind prospective study? 17 A. I was not privy to the 18 conversation between Doctor Thompson and Doctor 19 Leber, so I cannot comment on the veracity in 20 terms of wording of the use of the term best by 21 Doctor Thompson. 22 Q. The word best is used, is it 23 not? 24 A. The word best is used by Page 145 1 Doctor Thompson to relay a conversation he had 2 with Doctor Leber. 3 Q. He uses best in another 4 capacity, doesn't he, in this memo? 5 A. Would you like to explain 6 which one you mean? 7 Q. I'll show you. Page two, next 8 to the last paragraph, quote, Paul is taking the 9 position in talking with outside folks today that 10 Lilly and FDA and working together on the suicide 11 issue and following closely the post-marketing 12 events, but that there are no denominators and 13 the best that can be done is to put a "cap" on 14 the number of events, end quote. He uses best in 15 that connection also, doesn't he? 16 A. Yes, he does. 17 (PLAINTIFFS' EXHIBIT NO. 4 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Discussions of a prospective 21 study are also held physically between Lilly and 22 members of the Food and Drug Administration in 23 Washington, D.C., correct? 24 A. That's correct. Page 146 1 Q. And you in fact were present 2 at some of those meetings? 3 A. That's correct. 4 Q. You in fact were present on 5 September 25, 1990 when this issue was discussed. 6 A. That is correct. 7 Q. You know that, probably 8 because of independent recollection and because 9 you've got Exhibit 4 in front of you, correct? 10 A. That's correct. 11 Q. And at that time the 12 discussion centered around what they describe as 13 the most prominent issue being the spectrum of 14 suicidal behavior, correct? 15 A. That's what is written in the 16 exhibit you handed me. 17 Q. This is, by the way, Doctor 18 Wheadon, minutes of the meeting that occurred on 19 that date that were taken at the Food and Drug 20 Administration, this is an FDA document, not a 21 Lilly document, okay? 22 A. Okay. 23 Q. In other words this is not 24 Lilly's recount of the meeting, but is those Page 147 1 present at the Food and Drug Administration's 2 minutes of the meeting. Do you follow me? 3 A. Uh-huh. 4 Q. Is that a yes? 5 A. Yes, I do. 6 Q. There Lilly advised that 7 prospective trials were hampered by inability to 8 reach agreement with Doctor Teicher on 9 operational criteria, correct? 10 A. On operational criteria for 11 the phenomena that he described in his case 12 reports, that's correct. 13 Q. Did you ever talk with Doctor 14 Teicher? 15 A. Yes, I did. 16 Q. When? 17 A. I met with Doctor Teicher on 18 two occasions. 19 Q. Did you meet with him before 20 September 25, 1990? 21 A. Yes, I did. 22 Q. Tell me about the first 23 occasion that you met with him. 24 A. It was shortly after the Page 148 1 appearance of his series of case reports in the 2 American Journal of Psychiatry. 3 Q. I believe that was published 4 in the February, 1990 issue. 5 A. That's correct. 6 Q. So with that date in mind, 7 when was it that you went to -- 8 A. I don't recall the exact date, 9 but it was roughly a month or so following the 10 appearance of the article in the American 11 Journal. 12 Q. Did you go to McLean -- 13 A. Yes, I did. 14 Q. -- to visit with Doctor 15 Teicher? 16 A. Yes, I did. 17 Q. Who accompanied you on the 18 first visit? 19 A. Doctor Daniel Masica. 20 Q. What was the purpose of your 21 going to visit with Doctor Teicher? 22 A. To talk with him about -- 23 further about his cases that he had described in 24 the paper, and to see what additional information Page 149 1 he may have beyond what he provided in the 2 article. 3 Q. Tell me everything that you 4 can recall that was said in that meeting. 5 A. Again, it was a meeting that 6 happened sometime ago, so my recollection is on a 7 general nature. 8 Q. Did you take any notes during 9 that meeting? 10 A. I did not take notes, Doctor 11 Masica was taking notes. 12 Q. Okay. You saw Doctor Masica 13 taking notes? 14 A. Yes. 15 Q. Why didn't you take any notes? 16 A. There was no need for both of 17 us to be taking notes. Doctor Masica had offered 18 to take notes of the meeting, and I was doing 19 most of the talking with Doctor Teicher. 20 Q. Why were you selected to be 21 the spokesman, because you are a Harvard man? 22 A. Perhaps that or -- 23 Q. Doctor Teicher is not from 24 Texas? Page 150 1 A. Or it may be that I as a 2 psychiatrist could interact with Doctor Teicher 3 most sufficiently around what he was prescribing 4 his patients. 5 Q. Is Doctor Masica a 6 psychiatrist? 7 A. Doctor Masica is not a 8 psychiatrist. 9 Q. Go ahead, I interrupted you. 10 A. The general discussion was 11 around the six cases that he described in his 12 article in the American Journal. He saw those 13 patients over a span of a few years, they weren't 14 all in rapid succession. Those patients were of 15 what we call a difficult-to-treat variety, that 16 they had been on a host of different 17 antidepressant agents as well as other 18 medications. They had had very complicated 19 histories with very poor response to the 20 previously tried medications, including poor 21 response to Prozac. They had subsequently been 22 tried on other medications with equally poor 23 response. So this is really what we call a 24 refractory group of patients. Page 151 1 He described the phenomena as 2 he described in his paper, of an obsession with 3 thinking about suicide, something beyond what he 4 typically was accustomed to in his practice with 5 depressed patients. 6 Q. Did that seem to be the thing 7 that impressed Doctor Teicher, this obsession, 8 this going beyond what he would ordinarily see? 9 A. That seemed to be the thing 10 that was most triggering his noting these cases 11 as something unusual. 12 Q. Go ahead. 13 A. Doctor Teicher pointed out 14 that in his overall experience with Prozac, he 15 had not seen this, that he had used Prozac 16 successfully in other patients of his with no 17 such phenomena, and that he continues to use it 18 or continued to use it at the time I spoke with 19 him. He was at a loss to explain beyond the 20 hypothesis that he put forward in his paper. He 21 did not have additional medical information for 22 us other than providing the feedback that these 23 patients had been tried on other agents after 24 Prozac and had been equally refractory to Page 152 1 treatment. 2 Q. Doctor Teicher, I take it, 3 then, did not appear to you to be unreasonable in 4 his position concerning what he was seeing? 5 A. When you say unreasonable, 6 what do you mean? 7 Q. Well, in other words he 8 appeared to have some reasonable cause to be 9 concerned, that is his statement that this was 10 more of an obsession and more of a compulsion 11 than I had seen in other patients with Prozac? 12 A. Doctor Teicher was reasonable 13 in saying that this was different from what he 14 had seen in other patients. Not just other 15 patients on Prozac, in other patients. 16 Q. All right. Which lends 17 support to the fact that he appeared to be 18 approaching this with some scientific question? 19 A. In my discussion with Doctor 20 Teicher, he appeared to be approaching this with 21 some scientific question, yes. 22 Q. He didn't appear to be some 23 fringe player, did he? 24 A. In my discussion with Doctor Page 153 1 Teicher, I would not have described him as some, 2 quote, fringe player, no. 3 Q. Doctor Teicher was at the time 4 a respected member of the psychiatric community 5 in that area, wasn't he? 6 A. Doctor Teicher was a physician 7 on staff at McLean, with a faculty position at 8 the Harvard Medical School. If that's your 9 definition of a respected member of the 10 community, then yes, I guess you could describe 11 him as such. 12 Q. Don't you hold those 13 institutions with respect, Doctor Wheadon? 14 A. Again, I did not personally 15 talk to the members of the psychiatric community 16 about their opinion of Doctor Teicher, but 17 certainly given his affiliations, one could 18 assume that he was a respected member of the 19 medical community. 20 Q. And he didn't do anything in 21 his conversation to make you think otherwise? 22 A. In my discussion with Doctor 23 Teicher, again, it was a clinically 24 scientifically based discussion. Page 154 1 Q. Go ahead. 2 A. That really in a nutshell was 3 the discussion we had with him on that visit. 4 Q. On that visit, Doctor Teicher 5 agreed, did he not, to help Lilly in any way in 6 providing any assistance that was requested of 7 him by Lilly in examining this question further, 8 didn't he? 9 A. On that visit, Doctor Teicher 10 and we left the meeting with the agreement that 11 we would be in touch with him, and vice versa, he 12 very well was encouraged and asked to be in touch 13 with us for further information about these 14 cases, and information he may have on subsequent 15 cases in patients he's treating, any information 16 he may come into contact with concerning the 17 further histories of those patients. So it was 18 an agreement to maintain contact. 19 Q. All right. Did anything else 20 occur in that first meeting? 21 A. We did ask Doctor Teicher 22 where he arrived at the frequency rate he offered 23 in the conclusion of his paper. That being the 24 roughly three point five or three percent Page 155 1 frequency rate for this phenomena. He offered 2 back to us that originally when he submitted the 3 case reports, he did not have that figure in it, 4 the editorial review of the American Journal 5 wrote back saying can you give us some idea what 6 frequency this may be occurring at if it's a true 7 phenomena. He then arrived at the three percent 8 figure by asking the McLean pharmacy how many 9 prescriptions for Prozac had been written out of 10 the McLean pharmacy, and used that as his 11 denominator. So that is what he offered to us as 12 how he arrived at the three percent figure in his 13 paper. 14 Q. So he was saying those six 15 patients comprised three point five percent of 16 the total number of -- 17 A. Prescriptions for Prozac. 18 Q. -- prescriptions for Prozac at 19 the McLean Hospital? 20 A. Exactly. 21 Q. Did he give you any percentage 22 of what those six patients would represent versus 23 those other patients that he had treated with 24 Prozac? Page 156 1 A. No, he did not. 2 Q. Anything else in that 3 conversation? 4 A. That was pretty much the 5 extent of the conversation. 6 Q. When was your next 7 conversation with Doctor Teicher? 8 A. Some months later, I don't 9 remember, again, the exact date, but it may have 10 been on the order of five months, four months 11 later. 12 Q. Where did that conversation 13 take place? 14 A. Again, in his office at McLean 15 Hospital. 16 Q. And who was present at that 17 meeting? 18 A. On that visit, Doctor Bob 19 Zerbe accompanied me. 20 Q. What was the purpose of that 21 meeting? 22 A. To share with Doctor Teicher 23 the first round of analyses of the Lilly clinical 24 trial data base. Page 157 1 Q. Okay. Tell me about that 2 conversation or that meeting? 3 A. We have shared with Doctor 4 Teicher the analyses, the first round again, 5 looking at the basic rate of suicidal thinking or 6 suicidal acts in the clinical trials, showing 7 that there was no greater rate in the Prozac 8 group in the controlled clinical trials as 9 compared to placebo or the active control group, 10 and if anything there were fewer, quote, acts of 11 suicidal behavior or ideation in the Prozac or 12 active treatment groups as compared to placebo. 13 He welcomed the data as instructive, but he also 14 offered that that did not quite tap into what he 15 was describing, again this obsessive drive 16 towards suicidal thinking. And that in a 17 nutshell was the discussion around the data that 18 we presented to him. 19 Q. Did you or he or you all 20 express the opinion or the discussion -- have the 21 discussion that what Doctor Teicher was concerned 22 about was that there might be a particular 23 subgroup of individuals who were having this 24 particular reaction as opposed to general Page 158 1 depressed populations? 2 A. Doctor Teicher did offer the 3 opinion that this phenomena was so unusual, so 4 rare, and so discordant with his practice that 5 indeed it may be a different sort of patient than 6 your sort of run of the mill depressed patient. 7 Q. Did he in fact use the term 8 that there may be a subgroup of individuals who 9 are depressed that are having this particular 10 reaction to Prozac? 11 A. I don't recall him using the 12 exact term subgroup, but he may have, I don't 13 recall exactly. 14 Q. That would be at least an 15 accurate description of what you're saying? 16 A. That would be a description in 17 sync with what I've said, yes. 18 Q. In other words, I get from 19 what you're telling me, Doctor Teicher didn't 20 necessarily seem surprised or convinced or not 21 convinced one way or the other -- one way or the 22 other concerning the Lilly clinical trial data 23 because he would not necessarily have expected 24 the clinical trials to pick up this phenomena? Page 159 1 A. No, I would say that he was 2 not convinced or swayed or moved one way or the 3 other based on the data I presented him from the 4 clinical trials because we were looking at 5 suicidal ideation, behavior, or completed 6 suicides that occurred in the clinical trial, and 7 not focusing on this sort of narrowed down 8 obsessive drive towards suicidal thinking. So he 9 didn't take issue about the clinical trials, per 10 se, but the data that I presented him really did 11 not capture what he have felt he was describing. 12 Q. Do you agree that the clinical 13 trial data would not capture what he was 14 describing? 15 A. In light of the fact that no 16 one had described whatever this was before Doctor 17 Teicher, then it would be hard to say that the 18 trial data did or did not capture it because it 19 had not been described before. 20 Q. All right. Was this the first 21 time that the issue, that is this Doctor Teicher 22 article in February, 1990, was this the first 23 time that you had heard of anyone raising the 24 issue of a relationship between Prozac and Page 160 1 suicidality or violent aggressive behavior? 2 A. It was the first time I had 3 heard anyone raise the issue of Prozac promoting 4 an obsessive drive towards suicidal thinking as 5 described by Doctor Teicher. 6 Q. You seem to have qualified 7 your answer. My question is, is this the first 8 time you had ever heard about there being a 9 possible relationship between Prozac and 10 increased suicidal behavior? 11 A. It's the first time I recall 12 hearing someone offer the hypothesis that Prozac 13 may be associated with increased suicidal 14 behavior. 15 Q. Nobody at Lilly had ever made 16 you aware that this question had arisen before? 17 A. I don't recall anyone at Lilly 18 making me aware that this question had been 19 raised before. 20 Q. Don't you think you would 21 recall had that been put to you? 22 A. I don't recall that being put 23 to me. 24 Q. All right. Page 161 1 (OFF-THE-RECORD DISCUSSION.) 2 (PLAINTIFFS' EXHIBIT NO. 5 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. Doctor Wheadon, have you ever 6 seen Exhibit 5 before? 7 A. No, I have not. 8 Q. The reason I ask is because 9 this was supplied to us by Lilly as being 10 something that came from your file, and we have 11 not seen it before Lilly produced documents out 12 of your file, okay? 13 A. Uh-huh. 14 Q. Is that a yes? 15 A. I cannot accurately say that 16 this came from my file or not because I'm not 17 addressed in it. 18 Q. I understand that. 19 A. I inherited, at the time of 20 Doctor Wernicke's leaving, some of his files, and 21 it may indeed have been in there. 22 Q. I think probably what happened 23 was that you got part of Doctor Wernicke's file 24 when you came on, and then you maintained a part Page 162 1 of that as your file, is that correct? 2 A. Again, I got Doctor Wernicke's 3 file when he left, not when I came on. And this 4 may have been in the files that were given to me 5 at the time of Doctor Wernicke's leaving. 6 Q. Have you ever read this 7 before? 8 A. I do not recall ever reading 9 this before. 10 Q. Does it come as a surprise to 11 you? 12 A. I doesn't come as a strict 13 surprise, no. 14 Q. Sort of a surprise? 15 A. Not particularly. 16 Q. Why? 17 A. In point three, the questions 18 of suicides and possible activation was raised. 19 Doctor Blank seemed quite concerned about this. 20 He has a scientific interest in serotonin and the 21 mechanism of action of serotonin uptake 22 inhibitors. His concerns are about this class of 23 drug in general, not just fluoxetine. So around 24 the issue of serotonin reuptake inhibitors, Page 163 1 having in earlier studies an association with 2 activation, and subsequently proposing the 3 question of this relation to suicide, does not 4 surprise me. 5 Q. So you knew about that when 6 you met with Doctor Teicher, that there had been 7 earlier studies that raised the question of 8 activation and this could precipitate suicides or 9 suicidal thinking or violent aggressive behavior? 10 A. At the time I met with Doctor 11 Teicher, I was aware that there were some 12 thoughts in the scientific community about 13 serotonin reuptake inhibitors and activation, and 14 further some thoughts that activation may have an 15 effect on suicidal behavior, I was aware of that. 16 Q. Did you know that this was a 17 concern of the BGA, the German affiliate of the 18 FDA? 19 A. I was not aware of that being 20 a concern of the BGA. 21 Q. Did you know that that was the 22 reason that Lilly had had to withdraw their 23 application for marketing Prozac in Germany, 24 because the BGA raiseD concerns? Page 164 1 A. I'm not aware that Lilly 2 withdrew an application for Prozac in Germany 3 because of this concern. 4 Q. Were you aware that once Lilly 5 finally did get Prozac approved in Germany under 6 the trade name Fluctin, that it came with a 7 warning or contraindication concerning 8 suicidality? 9 A. I was not an involved in 10 labeling for Fluctin in Germany. 11 Q. Did you know that? 12 A. I was not aware of that. 13 Q. Do you know that now, did you 14 know that up until the time I told you? 15 A. I'm not familiar with the 16 labeling for Fluctin, that was not part of my 17 mandate in my performance of my employment at 18 Lilly. 19 Q. Weren't you at one time the 20 global clinical trial coordinator monitor? 21 A. No, I was not the global 22 clinical trial coordinator. Prior to my leaving 23 Lilly, I was designated as a global physician. 24 Q. Doctor Jeffrey Powell is Page 165 1 saying Doctor Wheadon is now the global monitor 2 of fluoxetine, on January 22, 1992. 3 A. That is Doctor -- Mister 4 Powell's term, I was designated the global 5 physician for fluoxetine. 6 Q. Were you the global physician 7 monitoring fluoxetine -- 8 A. For clinical trials. 9 Q. -- for clinical trials? 10 A. Yes. 11 Q. And yet you didn't know in 12 January, 1992 that Prozac or Fluctin in Germany 13 had a contraindication or a precaution with 14 respect to suicidal risk? 15 MR. FREEMAN: On patient types. It 16 had the same thing on diabetes and so forth, 17 don't try to mislead the witness. 18 A. As I mentioned before, I was a 19 global physician for clinical trials on Prozac. 20 The responsibility for labeling -- for the 21 language in labeling fell under the mandate of 22 two groups, international medical headed up by 23 Allen Weinstein, and the individual country 24 medical departments, headed up by the medical Page 166 1 directors in those countries. 2 Q. So you're giving me the reason 3 that you didn't know that. 4 A. I am telling you that I did 5 not know, and I'm telling you who in the company 6 would be most aware of those things. 7 Q. All right. Did you have any 8 discussions up to February, 1990 with anybody -- 9 any of these physicians at Lilly about Prozac 10 possibly causing activation and possibly causing 11 suicides? 12 A. I do not recall discussions 13 with the physicians at Lilly concerning Prozac 14 possibly causing suicide. I do recall 15 discussions concerning Prozac and possible 16 associated activation, as in quote meaning 17 adverse event terms that may be lumped under that 18 general term activation. 19 Q. Which terms did you lump under 20 activation? 21 A. You could include or exclude a 22 number of things, but some things that are 23 included under the general term activation 24 include anxiety, nervousness, agitation, the Page 167 1 three prime terms that fall in my mind under that 2 sort of general term. 3 Q. Anxiety, nervousness, 4 agitation. How about irritability? 5 A. Irritability in my mind would 6 not necessarily fall under activation. 7 Activation in my mind involves more of a sort of 8 nervousness, anxiety, agitation. Irritability 9 could be emotional, it could be motoric 10 irritability, there's a number of different 11 things. 12 Q. How about tremors? 13 A. Tremor would not fall under 14 activation. 15 Q. How about insomnia? 16 A. Would not fall under 17 activation necessarily. 18 Q. Why? 19 A. Because insomnia is not 20 necessarily indicative of an activated state? 21 Q. Even though it might be 22 indicative, it may be seen -- 23 A. A patient may be unable to 24 fall asleep because of being activated, but Page 168 1 that's not necessarily the reason for the 2 insomnia. 3 Q. So in that respect, it could 4 be included under activation? 5 A. Possibly, yes. 6 Q. How about anorexia? 7 A. No, it would not be included 8 under activation. 9 Q. How about weight loss? 10 A. No, it would not. 11 MR. FREEMAN: Lunchtime. I'm getting 12 activated and very irritable. 13 Q. Would irritability be 14 something you would characterize under 15 activation? 16 A. Again, as before, we discussed 17 irritability, there could be a number of 18 different things. 19 Q. Okay. 20 MS. ZETTLER: What if it's mapped to 21 nervousness as an event term? 22 THE WITNESS: As I mentioned, 23 nervousness would be an activation term. 24 MR. SMITH: Mister Freeman's getting Page 169 1 nervous and irritable, and activated. Let's 2 continue this after lunch. 3 (A LUNCH RECESS WAS TAKEN.) 4 Q. Doctor Wheadon, is there some 5 authority for the proposition that activation is 6 related to suicidality, suicidal ideation, 7 suicide attempts or completed suicide? 8 A. I don't quite understand what 9 you mean by authority. 10 Q. Is it mentioned and recognized 11 in the medical literature or psychiatric 12 literature that these situations can be related? 13 A. No, it's not recognized in the 14 psychiatric literature as a given that activation 15 and suicidality are linked. 16 Q. Whether they go hand in hand, 17 there has been, though, some impression that 18 activation can lead to suicidality in some 19 individuals? 20 A. There's been some discussion 21 in the literature that activation, whatever that 22 term may mean in the idea of the person forming 23 the idea, may not cause suicide, but because -- 24 but cause patients that are having suicidal Page 170 1 thoughts or suicidal intent to act out on those 2 thoughts or intent. 3 Q. That's fairly well recognized? 4 A. Again, it's not recognized as 5 a fact in medical literature or practice, it's a 6 proposal that's been put forth by some 7 individuals. 8 Q. And accepted by some in the 9 medical community? 10 A. There are some individuals 11 that accept that, yes. 12 Q. How about you? 13 A. I think it's a much more 14 complicated picture than that. 15 Q. Is that an 16 over-simplification? 17 A. What allows a patient to lose 18 that form of sort of control, that is to go from 19 having thoughts to acting out on the thoughts 20 with lethal intent, is not completely understood. 21 Q. But this activating concept is 22 one of the explanations as to what moves an 23 individual from thoughts to action? 24 A. The activation concept is one Page 171 1 of the ideas that have been put forth as what 2 propels a patient to attempt suicide, for some 3 patients. 4 Q. Yes, I'm not speaking -- it's 5 an absolute occurrence in every attempt, but that 6 it's recognized that that may be an explanation 7 in some attempts. 8 A. That is correct. 9 Q. Why is that, what do those who 10 propose that reasoning give as for the 11 explanation of that? 12 A. There are a number of 13 explanations. One may be that the patient is so 14 uncomfortable with their thoughts, with the sort 15 of physical manifestations of activation, that it 16 all sort of culminates with a loss of control, 17 that control to prevent one from taking or 18 attempting to take one's own life. 19 Q. What else? 20 A. It may just be a phenomena of 21 association, that there may be this connection of 22 suicidal behavior and activation in these 23 patients that happens to appear at the same time, 24 but one does not necessarily precede the other, Page 172 1 it's not the chicken or egg, it may just be that 2 they're symptoms that for whatever reasons sort 3 of tag along together, as such, or that's why you 4 see that association. 5 Q. All right. Has it been 6 explained that in some individuals that these 7 individuals become energized, however the 8 depressive symptoms are not relieved? 9 A. I think what you're asking is 10 there is some thought that in the beginning -- 11 the beginning stages of treatment of depression, 12 some of the symptoms begin to dissipate, one of 13 which may be lethargy, and lethargy is slowness 14 of movement, of speech, of willfullness. That 15 might respond such that the patient feels more 16 energetic. The patient feels more energetic, 17 nevertheless they still have some emotional 18 symptoms, depression, suicidal thoughts. 19 Q. Feeling of hopelessness? 20 A. Exactly. So with that sort of 21 discordance, the patient is more energetic, the 22 lethargy is lessened, but they still emotionally 23 feel down, hopeless, suicidal. That is a period 24 of particular concern for some patients, and that Page 173 1 might promote them to go ahead and have the 2 energy to make the attempt to take their lives. 3 Q. And activation has been 4 expressed in these terms. 5 A. Activation may be involved in 6 that scenario. It may be simply relief of 7 lethargy, which is not the same as being 8 activated. Do you see what I'm saying? 9 Q. Okay. What would be the 10 difference? 11 A. Lethargy as a symptom of 12 depression. Relief of lethargy, meaning patients 13 are coming out of a particular sort of slowed 14 state to a baseline state, is not the same as 15 going beyond baseline into what's termed 16 activation. 17 Q. So activation would be going 18 beyond baseline, relief of lethargy would be 19 going from below baseline up to baseline? 20 A. Exactly. 21 Q. And antidepressants have both 22 capacities in some individuals? 23 A. Antidepressants as a treatment 24 for depression should relieve the lethargic Page 174 1 component of depression in treating the 2 depression. And there have been some reports of, 3 as you say, activation-type symptoms, anxiety, 4 nervousness, agitation, what have you, associated 5 with antidepressant treatment. 6 Q. How long has this been known? 7 A. I'm not sure how long this has 8 been a point of discussion in practice and in the 9 literature. Certainly I would say it's been a 10 discussion point for the better part of the 11 latter part of the '80s, mid to latter part of 12 the '80s, into the '90s. 13 Q. All right. Was that something 14 that was being discussed when you were in medical 15 school? 16 A. There were discussions when I 17 was in medical school about -- as I mentioned, 18 the period of concern or particular attention in 19 treating depressed suicidal patients, you may 20 have that discordant response where the lethargy 21 relieves itself or is relieved, but the patients 22 are still emotionally down-trodden, depressed, 23 suicidal. With that discordance the patient may 24 have more energy and ability to attempt to take Page 175 1 their lives. 2 Q. But again, that's different 3 from the activation? 4 A. Exactly. 5 Q. When was it that the 6 activation became recognized? 7 A. I don't know exactly when that 8 discussion initiated in the literature, I can't 9 give you an exact date on that. 10 Q. All right. Do you recall that 11 as being something that was mentioned in medical 12 school or in your residency? 13 A. If I recall correctly, it's 14 something that was more in keeping with what I 15 was learning in residency as opposed to medical 16 school. 17 Q. Have you done any special 18 studies or made any particular research projects 19 into suicidality? 20 A. No, I have not. 21 Q. Do you follow what I'm saying, 22 in other words have you attempted to study a 23 great number of suicidal patients or read a great 24 deal of literature on suicidality as opposed to Page 176 1 an average psychiatrist, if there is such a 2 thing? 3 A. I would say that my readings 4 or my studies have not gone so in depth into the 5 field of suicide separate from my work at Lilly, 6 prior to joining Lilly, that would make me stand 7 at odds with your, quote, average psychiatrist. 8 Q. You don't profess to know more 9 about the mechanism of suicide than the average 10 well-trained psychiatrist? 11 A. No, I do not. 12 MR. COLEMAN: That just cut out three 13 hours of questioning, that was excellent. 14 (PLAINTIFFS' EXHIBIT NO. 6 WAS 15 MARKED FOR IDENTIFICATION AND 16 RECEIVED IN EVIDENCE.) 17 Q. Exhibit 6 is a Telex or some 18 form of communication between your German office 19 and the home office in Indianapolis, is it not? 20 A. As best I can tell, it appears 21 to be that. 22 Q. Obviously the date of this is 23 June 26, 1984, is it not? 24 A. That's the date at the top of Page 177 1 the document, yes. 2 Q. And it would precede your 3 joining Lilly? 4 A. That is correct. 5 Q. But would be about the time 6 that you started your residency in psychiatry? 7 A. Just prior to going into 8 psychiatric residency, that is correct. 9 Q. This is a request from 10 Germany, is it not, for additional data in 11 connection with discussions with the BGA in June 12 of '84, which was the -- is the equivalent of the 13 U.S. FDA, correct? 14 A. That's what it appears to be. 15 Q. Item seven indicates that the 16 BGA had explained their reservations regarding 17 CNS side effects, correct? 18 A. That is what item seven reads. 19 Q. Item ten indicates that the 20 BGA was concerned with respect to, quote, 21 comparative use of concomitantly taken hypnotics 22 and benzodiazepines in agitated retarded 23 fluoxetine patients versus agitated retarded 24 patients on comparitors. Reason, the BGA Page 178 1 suspects fluoxetine to be a stimulating 2 activating drug, paren, side effect profile, 3 suicide, suicide attempts, close paren, period, 4 correct? 5 A. That's what number ten reads. 6 Q. Were you aware that the BGA in 7 1984 considered or suspected fluoxetine to be a 8 stimulating activating drug? 9 A. No, I was not. 10 Q. With the side effect profile 11 of suicides and suicide attempts? 12 A. That is not exactly what the 13 number ten says, but I was not aware of that. 14 Q. Well, it says side effect -- 15 activating drug, paren, side effect profile, 16 suicides, suicide attempts, close paren, does it 17 not? 18 A. It reads activating drug, 19 paren, side effect profile, comma, suicides, 20 comma, suicide attempts, close paren, period. 21 Q. With respect to fluoxetine, 22 it's using those words in connection with 23 fluoxetine, is it not? 24 A. But it's not implying suicides Page 179 1 were a part of the side effect profile the way I 2 read it. 3 Q. However you read it, I've read 4 it correctly, have I not? 5 A. Including the commas, yes. 6 Q. Well, I understand that you 7 don't agree that Prozac has a side effect profile 8 of suicide, I'm not arguing at all with you about 9 your belief on that. My question is do you know 10 that the BGA, the German equivalent to the FDA, 11 was suspecting Prozac to be a stimulating 12 activating drug? 13 A. I did not know that the BGA 14 had that suspicion. 15 Q. And the side effect profile of 16 suicides or suicide attempts? 17 A. I repeat, in my reading number 18 ten, suicides and suicide attempts are not part 19 of the side effect profile. 20 Q. What do you think they're 21 talking about there when they say "suicides, 22 suicide attempts" if you don't think they're 23 talking about the side effect profile? 24 A. As I've stated, it says Page 180 1 activating drug, paren, side effect profile, 2 comma, suicides, comma, suicide attempts, close 3 paren, period. 4 Q. If they're not speaking about 5 suicide and suicide attempts in connection with 6 Prozac, what are they talking about? 7 A. I was not at Lilly at the 8 time, I was not privy to the conversation, I have 9 no idea. 10 Q. So you're going to have to 11 take it just like I take it, whatever it says, it 12 says, doesn't it? 13 A. Right, it says what it says, 14 that's correct. 15 Q. Fourteen says, quote, as we 16 already explained by our Telex to Doctor Zerbe on 17 June 8, 1984, we need a careful analysis of 18 suicides and suicide attempts, patient by 19 patient, symptomatology, severity upon entry into 20 the study, and week by week until the event 21 occurred, dose of fluoxetine, side effects, et 22 cetera. This is a very serious issue in the 23 opinion of the BGA. It might well be that we 24 will have to recommend concomitant tranquilizer Page 181 1 intake for the first two to three weeks in the 2 package literature, period, end quote, is that 3 correct? 4 A. That's what number fourteen 5 reads. 6 Q. Were you aware that in the 7 opinion of the BGA, this was a very serious 8 issue? 9 A. I was not aware of that, no. 10 Q. Did you talk to Doctor Zerbe 11 about this careful analysis of suicides and the 12 fact that the BGA considered this a serious 13 issue? 14 A. No, I did not. 15 Q. Did you ever have any 16 discussion with Doctor Zerbe concerning 17 concomitant tranquilizer intake for the first two 18 or three weeks? 19 A. Not that I recall. 20 Q. Are you aware of any 21 concomitant tranquilizer intake in connection 22 with Prozac? 23 A. You have to be more specific 24 in your question. Page 182 1 Q. In any clinical trials. 2 A. In clinical trials with 3 Prozac, concomitant usage of chloral hydrate for 4 the most part was allowed in some of the 5 protocols. 6 Q. How about benzodiazepines? 7 A. I'm aware that in some of the 8 earlier protocols, benzodiazepines were allowed 9 as concomitant treatment. 10 Q. What was the reason for that 11 as per your understanding? 12 A. I'm not sure of the reason for 13 that because I was not at Lilly at the time those 14 trials were done, I'm just aware that those were 15 part of the accepted concomitant medications in 16 those protocols. 17 Q. Chloral hydrate is a sleeping 18 medication, is it not? 19 A. That's correct. 20 Q. Benzodiazepines are 21 anti-anxiety agents, aren't they? 22 A. Benzodiazepines are used as 23 both anti-anxiety drugs as well as drugs to 24 assist with sleep. Page 183 1 Q. They're primarily 2 tranquilizers, though, are they not? 3 A. I don't think that I can say 4 they're primarily used one way or the other. 5 Q. Is, Doctor Wheadon, 6 benzodiazepines a tranquilizer? 7 A. Benzodiazepines are 8 technically anxiolytics. 9 Q. Which is? 10 A. Drugs intended to treat 11 anxiety. 12 Q. And is a tranquilizer and a 13 drug to treat anxiety the same thing? 14 A. Not necessarily. 15 Q. Give me an example of a 16 tranquilizer that's not an anti-anxiety 17 medication? 18 A. One could technically view 19 chloral hydrate as a tranquilizer, and it's not 20 necessarily used to treat anxiety. 21 Q. All right. Anything then that 22 is used to induce sleep or lessen anxiety, you 23 would consider a tranquilizer? 24 A. Tranquilizer is used as a Page 184 1 general term to include both anxiolytics and 2 sedatives, that's correct. 3 (PLAINTIFFS' EXHIBIT NO. 7 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you ever seen Exhibit 7 7 before? 8 A. No, I have not. 9 Q. Exhibit 7 is a document 10 apparently done in April of 1985 by the German 11 affiliate in Bad Homburg transmitted to various 12 officials throughout the world, including Doctor 13 Weinstein, Doctor Wernicke, and Doctor Zerbe in 14 Indianapolis, correct? 15 A. That's what appears to be the 16 case, yes. 17 Q. Apparently from looking at 18 Exhibit 7, it appears that there were 19 representatives of Lilly in Germany who had hired 20 an expert to review Prozac data to give them 21 advice on registering Prozac in Germany, correct? 22 A. It seems as if they met with 23 an outside consultant to discuss fluoxetine data. 24 Q. If you look on the last page Page 185 1 of the document, it appears that that outside 2 consultant is a gentleman by the name of 3 Herrmann, with two Rs and two Ns. 4 A. I have no way of knowing who 5 the outside person was. 6 Q. Have you ever heard of a 7 Professor Herrmann -- 8 A. No, I have not. 9 Q. -- who is a consultant in 10 Germany? 11 A. No, I have not. 12 Q. When you were in Europe and 13 met with the European leaders, was a Doctor 14 Herrmann there? 15 A. No, there was no Professor 16 Herrmann. 17 Q. There were individuals from 18 West Germany, were there not, in your -- when you 19 met in 1990, five years later? 20 A. That's correct. 21 Q. Who were the psychiatrists 22 from West Germany that were at that meeting? 23 MR. MYERS: You can answer that. 24 A. If I recall, I met with a Page 186 1 Professor Moeller, M-O-E-L-L-E-R. And I think 2 that might have been the only consultant I met 3 with in Germany. 4 Q. Where was the meeting? 5 A. If I remember correctly, we 6 met in Bohn. 7 Q. Germany? 8 A. Yes. 9 Q. Did you know about Exhibit 7 10 and about this meeting that had been held back in 11 1985 with the German consultant? 12 A. No, I did not. 13 Q. Had you ever seen this 14 document before that? 15 A. No, I have not. 16 Q. Have you ever seen this 17 document before today, Doctor Wheadon? 18 A. No, I have not. 19 Q. Are you familiar with the data 20 that they were reviewing in connection with that 21 meeting? 22 A. No, I'm not. 23 Q. Well, you know what protocol 24 number twenty-seven is, don't you? Page 187 1 A. No, I do not. 2 Q. Well, you know that there was -- 3 protocol number twenty-seven was a double-blind 4 placebo controlled trial involving fluoxetine and 5 Imipramine, do you not? 6 A. The statement on the document 7 you have in front of me is an analysis of pooled 8 studies, fluoxetine versus Imipramine versus 9 placebo, paren protocol number twenty-seven, 10 close paren. 11 Q. You've seen protocol number 12 twenty-seven, have you not? 13 A. I do not recall seeing a 14 specific protocol entitled number twenty-seven. 15 Q. You're familiar with that 16 study, though, aren't you? 17 A. Again, not having been part of 18 this group, I cannot say I know exactly which of 19 the many studies protocol number twenty-seven 20 refers to. 21 Q. Did you know that the study, 22 whatever -- by whatever protocol it was termed, 23 comparing fluoxetine versus Imipramine versus 24 placebo, was a pivotal clinical trial submitted Page 188 1 by Lilly to the United States Food and Drug 2 Administration? 3 A. There were a number of studies 4 with fluoxetine, Imipramine and placebo submitted 5 to the U.S. Food and Drug Administration and the 6 fluoxetine NDA. 7 Q. So is the answer to my 8 question, I don't know? 9 A. The answer to my question is I 10 cannot identify which study this particular 11 protocol is referring to. 12 Q. Was there more than one 13 protocol that had a three-arm study such as this? 14 A. Yes. 15 Q. How many? 16 A. I do not recall how many. 17 Q. On page two under safety, in 18 bold type, the next to the last bullet point 19 says, quote, still not resolved is the fact that 20 suicide attempts have been observed more 21 frequently on fluoxetine as compared to 22 Imipramine, paren, only epidemiologic data or 23 literature or other antidepressants may help to 24 identify whether it happened by chance an Page 189 1 incidence of suicide attempts was abnormally high 2 on fluoxetine or abnormally low on comparitors, 3 close paren, period, end quote, correct? 4 A. That's what the statement 5 says. 6 Q. Have you ever seen that 7 statement before? 8 A. No, I have not. 9 Q. Are you familiar with any 10 study where there was a finding that suicide 11 attempts were observed more frequently on Prozac 12 as compared to Imipramine? 13 A. I'm not familiar with any one 14 study where that finding was established. 15 Q. Are you aware of any study at 16 all where Prozac was found to have a more 17 frequent incidence of suicide attempts as 18 compared to Imipramine? 19 A. In the retrospective analysis 20 of the placebo controlled double-blind clinical 21 trials that Lilly carried out, the gross number 22 of suicide attempts was greater in the fluoxetine 23 group than in the comparitor group. If you then 24 look at the number of patients exposed and Page 190 1 calculate the rate of suicide attempts per 2 patient year of exposure, the rates were 3 comparable. 4 Q. It doesn't say anything about 5 that here, does it, Doctor? 6 A. No, it does not because they 7 had not gone to that additional study. 8 Q. How do you know? 9 A. That's my assumption. 10 Q. You weren't even there in 11 1985. 12 A. That's my assumption. 13 Q. Why are you making that 14 assumption? 15 A. I'm allowed to assume just as 16 much as anyone else, and that's my assumption, 17 based on what you've given me to read. 18 Q. I wasn't there and you weren't 19 there. 20 A. That's correct. 21 Q. All I can see is it says here 22 in English, look with me, that the suicide 23 attempts have been observed more frequently on 24 fluoxetine as compared to Imipramine, doesn't it? Page 191 1 A. That's what the statement 2 says. 3 Q. The first page says in 4 connection with the data reviewed that they 5 reviewed an analysis of pooled studies, 6 fluoxetine versus Imipramine versus placebo, 7 doesn't it? 8 A. The statement reads analysis 9 of pooled studies, yes. 10 Q. So that would indicate to me 11 that they had performed that analysis that you 12 spoke of earlier. 13 A. That is incorrect. 14 Q. When was that analysis made? 15 A. Which analysis are you 16 referring to? 17 Q. The analysis that you speak 18 of, where you say that all of a sudden they put 19 patient years to it. 20 A. The analysis I'm referring to 21 is the analysis of the placebo controlled 22 double-blind clinical trial data on Prozac with 23 comparitor drugs and placebo. 24 Q. Imipramine? Page 192 1 A. Imipramine was included. 2 Q. All right. 3 A. That analysis, upon which 4 Doctor Beasley's paper in the British Medical 5 Journal is based, showed that in terms of gross 6 rate, the number of suicide attempts, there were 7 more on fluoxetine than on the comparitor group. 8 If you then factor in the denominator the number 9 of patients exposed, and you get what we call an 10 ingested rate, rate per patient exposure year. 11 Q. I understand that. 12 A. If you look at that rate, it 13 is comparable between Prozac and the active 14 comparitor group. 15 Q. Do you think that this is 16 wrong that they observed suicide attempts more 17 frequently on fluoxetine as compared to 18 Imipramine? 19 A. When you asked me do I think 20 that this is wrong, what do you mean? 21 Q. Incorrect, inaccurate. 22 A. If you're asking me if I find 23 the statement that the number of attempts, gross 24 attempts, gross number of attempts, calculated Page 193 1 for the fluoxetine group exceeded that calculated 2 for the Imipramine group, not accounting for the 3 denominator, then as I mentioned, that is a 4 correct statement. Not accounting for the 5 denominator for both groups. 6 Q. All right. Why do you think 7 there wasn't any account made for the denominator 8 if this was a consultant and this material was 9 being submitted to the BGA in Germany? 10 A. I cannot explain that, I was 11 not present. 12 Q. Wouldn't this just have to be 13 a consultant that wasn't using any kind of brains 14 whatsoever to make this statement? 15 A. I don't know who the 16 consultant was. 17 Q. Well, you're making an 18 assumption that that consultant is not making an 19 accurate analysis, aren't you? 20 A. I'm making a statement that my 21 reading of this indicates they are only comparing 22 the gross number of suicide attempts, and not 23 accounting for the denominator. 24 Q. It doesn't say that, though, Page 194 1 does it? 2 A. It also does not say that. 3 Q. Have you ever seen the 4 twenty-one page typewritten report that this 5 expert left? 6 A. I have not seen the twenty-one 7 page typewritten report cited in this document. 8 Q. Do you think that might give 9 us some benefit of whether or not the correct 10 analysis was made? 11 A. I have no idea. 12 Q. This is a summary, isn't it, 13 can't you tell this is a summary, what's being 14 said here? 15 A. What I have in front of me 16 appears to be a recollection of a meeting, I have 17 no idea if it's a summary of the report or what. 18 Q. Well, look at the last 19 sentence on page one, it says the essential 20 points are summarized as follows. 21 A. Okay. 22 Q. It says Professor Blank left 23 an opinion of twenty-one typewritten pages. The 24 essential points are summarized as follows. Page 195 1 Doesn't it say that? 2 A. Okay, it does say that. 3 Q. So I get the impression that 4 everything on page two and three is a summary of 5 this twenty-one page report, don't you? 6 A. That is what the document 7 says, I have no idea, I have not seen this before 8 nor the twenty-one page typewritten report. 9 Q. Do you think that would be of 10 benefit to see that twenty-one page typewritten 11 report? 12 A. Quite possibly. I have no 13 idea. 14 Q. Are you aware of any study 15 where the incidence of suicide was abnormally 16 high on Prozac? 17 A. I was not aware of any study 18 where the incidence of suicide was abnormally 19 high on Prozac, no. 20 Q. Are you aware of any study 21 where the incidence of suicide was abnormally low 22 on comparitor drugs? 23 A. I'm not aware of such study. 24 Q. Are you aware of any instance Page 196 1 where it just happened by chance that there was 2 an abnormally high number of suicide attempts on 3 Prozac? 4 A. I'm not aware of such. 5 Q. Are you aware of any instance 6 where it just happened by chance that there was 7 an abnormally low number of suicides under 8 comparitor drugs? 9 A. I'm not aware of such. 10 Q. In the data that you have seen 11 with respect to the comparison of Prozac and 12 placebo and Imipramine, is that data that's 13 mentioned by Doctor Beasley in the meta-analysis? 14 A. The third group in the 15 meta-analysis is active comparitor, which 16 includes Imipramine, but not solely Imipramine. 17 Q. All right. So have you seen 18 any data on the trial or trials that compared 19 only Prozac versus placebo versus Imipramine? 20 A. Again, the data that I'm 21 familiar with included Imipramine, but was not 22 solely Imipramine. 23 Q. My question is, solely Prozac 24 versus placebo versus Imipramine? Page 197 1 A. I do not recall seeing that 2 data. 3 Q. You know there are studies 4 that used those three criteria, don't you? 5 A. Yes. 6 Q. But you're not familiar with 7 that data, are you? 8 A. I'm not familiar with looking 9 at Imipramine as the only comparitor. 10 Q. So you don't have any way to 11 dispute what this says in this paragraph 12 concerning placebo versus Prozac versus 13 Imipramine, do you -- 14 A. I don't have -- 15 Q. -- because you haven't seen 16 the data? 17 A. I have nothing in front of me 18 to dispute what's written in this document. 19 Q. And you have never seen 20 anything that disputes what's written in this 21 document either, have you? 22 A. Yes, I have seen data to 23 dispute what's written in this document. 24 Q. And comparing placebo, Prozac Page 198 1 and Imipramine only? 2 A. Not comparing Imipramine only, 3 it's all comparitors, primarily Imipramine -- 4 Q. I'm not talking about all 5 comparitors, I'm talking about Imipramine only. 6 A. Okay. I've answered your 7 question. 8 Q. All right. That is that 9 you've not seen that data? 10 A. On Imipramine alone, that is 11 correct. 12 Q. Is Imipramine a tricyclic 13 antidepressant? 14 A. Yes, Imipramine is a 15 tricyclic. 16 Q. What is the brand name of 17 Imipramine? 18 A. I'm actually, quite frankly, 19 blanking on the brand name of Imipramine, it's 20 been around as a generic for so long. 21 Q. Do you know if any of the 22 consultants that you saw in 1990 in Europe had 23 seen any twenty-one page opinion from some expert 24 or consultant that had been hired by Lilly to Page 199 1 help him with the registration process of Prozac 2 in Germany? 3 A. I'm not aware that any of the 4 consultants I discussed data with had seen a 5 twenty-one page typewritten report by a 6 consultant of Lilly in 1985. 7 Q. Would it concern you, Doctor 8 Wheadon, if there was data, double-blind placebo 9 controlled data, comparing Prozac, placebo and 10 Imipramine that showed a greater incidence of 11 suicide attempts on Prozac? 12 A. Not in and of itself, no. 13 Q. What else would you need to be 14 concerned? 15 A. I would have to look at the 16 denominator for the various treatment groups and 17 the relative amounts of time the patient spent on 18 the various treatments. 19 Q. All right. Assume that the 20 denominators and the time spent were the same. 21 A. If the -- if what you're 22 saying to me is that the denominators were 23 comparable, time spent was comparable, the 24 adjusted rate, the rate per patient, exposure Page 200 1 year, was greater for fluoxetine than for 2 Imipramine, that would raise a question in my 3 mind, that is correct. 4 Q. Concerning the fact that 5 Prozac, in that particular trial, would be 6 indicative of a causal relationship for suicide? 7 A. No, it would not be indicative 8 of a causal relation, it would raise a question 9 in my mind is what I said. 10 Q. Concerning whether or not 11 Prozac could cause suicidality? 12 A. What the cause for the greater 13 rate was, that's the question. 14 Q. Are you familiar with the 15 Hippius report? 16 A. No, I'm not. 17 Q. Are you familiar with the 18 Hippius trial? 19 A. No, I'm not. 20 Q. Were you reasonably familiar 21 when you were the global monitor for Prozac of 22 all of the trials that had been done while you 23 were up to that point? 24 A. In my role as global physician Page 201 1 for fluoxetine, I was responsible for ongoing 2 clinical trials of fluoxetine. 3 Q. So if there had been a trial 4 by the name of Hippius that had been completed, 5 you might not be aware of that? 6 A. That is correct. 7 Q. Do you know of any effort that 8 was taken by Lilly in connection with the bottom 9 of page three of this document to, quote, 10 determine certain type of patients who will 11 better respond to fluoxetine than to Imipramine 12 so that higher risk might be acceptable, end 13 quote? 14 A. I don't see exactly where you 15 are. 16 Q. Last sentence of the page, 17 under benefit risk ratio. 18 MS. ZETTLER: The second page. 19 Q. It's got two at the top and 20 three at the bottom, why, I don't know. 21 A. I'm not aware, again, of this 22 document, nor am I aware of any effort on Lilly's 23 part to address the issue raised in point C on 24 page two of this document. Page 202 1 Q. Are you aware of or -- well, 2 first question is, are you aware of any improper 3 selection of patients in the Prozac clinical 4 trials? 5 A. No, I'm not. 6 Q. Have you ever expressed any 7 criticism concerning possible improper selection 8 of patients in Prozac clinical trials? 9 A. No, I'm not. 10 Q. Are you aware of any 11 improprieties or anything that had been withheld 12 from reporting requirements of the Food and Drug 13 Administration by Lilly in connection with the 14 Prozac clinical trials? 15 A. No, I'm not. 16 Q. Have you ever made any 17 criticism with respect to the conduct of the 18 Prozac clinical trials? 19 A. No, I have not. 20 Q. Have you ever written any 21 criticism of any nature? 22 A. No, I have not. 23 Q. Ever expressed any criticism 24 of Doctor Teicher, Leigh Thompson or Bob Zerbe? Page 203 1 A. The first name? 2 Q. Gary Teicher. 3 MR. FREEMAN: Tollefson. 4 MS. ZETTLER: Teicher. 5 A. Gary Teicher is not a doctor, 6 so that's why I'm confused. 7 Q. Have you expressed any 8 criticism to him concerning the conduct of the 9 Prozac clinical trials? 10 A. I have not expressed criticism 11 to any individual concerning the conduct of 12 clinical trials by Lilly on Prozac. 13 (PLAINTIFFS' EXHIBIT NO. 8 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.). 16 Q. Exhibit 8 is a translation of 17 the German package insert, Doctor Wheadon, you'll 18 have to take my word for that. Will you do that? 19 A. Well, as a translation done 20 by, I assume, Berlitz, since that's on the 21 document. 22 Q. Right. Turn to page two of 23 the translation itself. 24 A. If you don't mind, I would Page 204 1 like to read through the document. 2 Q. I'm sorry, I didn't give you 3 time to do that. 4 A. I do want to ask you one 5 question. You mentioned that this is a 6 translation of the package insert, however in 7 reading it, it appears to be instructions to 8 patients. 9 Q. Prescribing information. 10 A. Well, there's a difference 11 between prescribing information for physicians 12 and instructions to patients. 13 Q. All right. This is something 14 then that was intended for patients? 15 A. It appears to be that based on 16 the translation. 17 Q. Okay. So this is something 18 that a patient would get? 19 A. For example, under 20 contraindication, it reads in order for your 21 doctor to be able to carefully weigh the benefits 22 and risks of treatment, you should tell him about 23 everything about your health condition and life 24 circumstances. Page 205 1 Q. So this is not instructions 2 for the doctor? 3 A. Again, based on the 4 translation, it appears that it's instructions 5 for the patient. 6 Q. And it's not pointing to a 7 doctor, various patients that might be at risk, 8 is it? 9 A. I don't understand your 10 question. 11 Q. It's not pointing to a doctor 12 various patients that might be at risk for 13 particular events, is it? 14 A. The document seems to be 15 intended for patients. 16 Q. So it's not pointing -- giving 17 any information for the doctor in selecting 18 patients who might be at risk, correct? 19 A. I will answer your question 20 that, again, the document is intended for 21 patients in Germany. My understanding is there 22 is also a package insert intended for the 23 physician. 24 Q. But this is intended for the Page 206 1 patient, isn't it? 2 A. What you have given me seems 3 to be a translation for the patient. 4 Q. So it can't be any kind of 5 document that's intended to identify for doctors 6 particular patients who might be at risk for 7 particular adverse events, can it? 8 A. Technically speaking, it 9 appears that the document is intended as an 10 information piece for patients, and not for 11 physicians. 12 Q. And it's not pointing to 13 physicians particular patients who might be at 14 particular risk for particular reactions, is it? 15 A. In light of the fact that the 16 document is addressing the patient and not 17 physicians, then it's not pointing out to 18 physicians the various considerations in using 19 the drugs, it's intended for patients. 20 Q. And prescribing the drugs? 21 A. Right. Again, it's intended 22 for patients, not for the prescriber. 23 Q. Now, on page two, it 24 identifies -- it has a heading under risk Page 207 1 patients, does it not? 2 A. The translation that I have 3 reads risk patients. 4 Q. Under that it has risk of 5 suicide, does it not? 6 A. Translation that I have reads 7 risk of suicide, yes. 8 Q. Do you think that there's 9 something wrong with this translation, Doctor 10 Wheadon? 11 A. I have no way of verifying the 12 translation as being correct. 13 Q. Do you think it's incorrect? 14 A. I have no way of verifying the 15 translation as being correct or incorrect. 16 You've just given me an English translation of 17 what was described as the package insert for what 18 appears to be information for patients. 19 Q. Do you know of any information 20 that -- do you speak German? 21 A. No, I do not. 22 Q. It says there risk of suicide, 23 doesn't it? 24 A. That's what the translation Page 208 1 reads. 2 Q. It says Fluctin does not have 3 a general sedative effect on the central nervous 4 system, doesn't it? 5 A. That's what the translation 6 reads. 7 Q. Fluctin is Prozac in Germany, 8 isn't it? 9 A. Fluctin is the German name for 10 Prozac, yes. 11 Q. It says, therefore, for 12 his/her own safety, the patient must be 13 sufficiently observed until the antidepressive 14 effect of Fluctin sets in, correct? 15 A. That is what the translation 16 reads. 17 Q. It says, additionally, taking 18 an additional sedative may be necessary, correct? 19 A. That is what the translation 20 reads. 21 Q. This also applies in cases of 22 extreme sleep disturbances or excitability, 23 doesn't it? 24 A. That's what the translation Page 209 1 reads. 2 Q. Do you have any reason to 3 believe whatsoever, Doctor Wheadon, that this is 4 an improper or inaccurate translation, what I 5 have just read? 6 A. I have no ability to render an 7 opinion on the correctness or incorrectness of 8 the translation. 9 Q. Do you agree that Fluctin or 10 Prozac does not have a general sedative effect? 11 A. I agree with the statement, in 12 general, Prozac or Fluctin does not have a 13 general sedative effect. 14 Q. Do you agree that a patient 15 must be sufficiently observed while on Prozac? 16 A. I agree that a patient must be 17 sufficiently observed on any antidepressant, also 18 Prozac. 19 Q. Including Prozac. Do you 20 agree that taking an additional sedative may be 21 necessary in connection with the use of Prozac? 22 A. I agree that in some patients 23 a sedative may be indicated, and using an 24 antidepressant, including Prozac. Page 210 1 Q. And in fact that was done 2 during the clinical trials on Prozac, wasn't it? 3 A. Chloral hydrate, as I 4 mentioned, were allowed in protocols to assist 5 patients who were having difficulty sleeping. 6 Q. Do you agree that a sedative 7 may be necessary if there is in cases of extreme 8 sleep disturbances or excitability? 9 A. I agree that may be indicated 10 in using an antidepressant, including Prozac. 11 Q. Have you seen excitability 12 reported in connection with Prozac? 13 A. I have seen terms that might 14 equate with excitability, such as anxiety, 15 agitation and nervousness. 16 Q. Would excitability fall under 17 this general heading of activation, Doctor 18 Wheadon? 19 A. It could possibly. 20 Q. Have you seen in extreme sleep 21 disturbance as a result of ingestion of Prozac? 22 A. I have seen reports of 23 difficulty falling asleep, staying asleep, in 24 association with Prozac use, yes. Page 211 1 Q. So is there anything 2 inaccurate in connection with what we've read 3 about the properties of Prozac in the German 4 information that's given to Germans who are 5 taking Prozac? 6 MR. FREEMAN: Objection, the document 7 you're referring to talks about risk patients, 8 not Prozac risk, and the question states 9 something that's not in evidence and can never be 10 in evidence. 11 MR. SMITH: How can he ever know that 12 something will never be in evidence. 13 (DISCUSSION OFF THE RECORD.) 14 Q. He's making an objection, but 15 you can answer the question. We'll read it back 16 for you if it would help you, Doctor Wheadon. 17 A. Would you repeat the question? 18 (THE COURT REPORTER READ BACK THE 19 REQUESTED TESTIMONY.) 20 A. I find that I cannot answer 21 that question because it's vague in nature. 22 Q. How could I clear it up for 23 you so you might be able to answer that question 24 for us, Doctor Wheadon? Page 212 1 A. You asked me if there's 2 anything inaccurate concerning the sections of 3 the German translation that we read. 4 Q. Yes, sir. 5 A. If that is your question, the 6 section that we read under risk patients, 7 subsection risk of suicide, the sections we read 8 from that particular part of this translation, as 9 I indicated, I have no difficulty with. 10 Q. Do you have difficulty with 11 any of it? 12 MR. FREEMAN: Any of that section? 13 MR. SMITH: Yes. 14 A. Any of the section risk 15 patients, risk of suicide, we've gone through 16 sentence by sentence, and I've agreed that -- I 17 agree with those statements. 18 Q. All right. Would you have any 19 objection to patients in the United States having 20 this information? 21 A. When you say patients in the 22 United States having this information -- 23 Q. Yes, sir. 24 A. -- what do you mean? Page 213 1 Q. That this is information going 2 into the package insert in the United States? 3 A. The information contained in 4 this translation is, as I mentioned, information 5 for patients, and a similar document does not 6 exist in the United States. 7 Q. Would you object if a similar 8 document did exist and patients in the United 9 States would be given this information? 10 MR. FREEMAN: Objection, it's not 11 permitted under the FDA rules, we can't do 12 anything about that. 13 MR. SMITH: He can still answer the 14 question. 15 A. As counsel has indicated, the 16 FDA does not allow prescribing information 17 specifically for patients. 18 Q. All right, let's say that you 19 had a patient on Prozac, as a psychiatrist, would 20 you have any objection to giving that patient 21 this information? 22 A. As a psychiatrist, if I had a 23 patient on Prozac, I would have no objection in 24 indicating to them that Prozac has no sedative Page 214 1 effect on the central nervous system in general, 2 that for his or her own safety we needed to 3 continue to observe the patient closely until the 4 antidepressant effect of Prozac set in, that the 5 patient may need to take an additional sedative 6 if they're having difficulty with sleep. I would 7 have no objection with that. 8 Q. Or excitability? 9 A. Or excitability, if you wanted 10 to use that language as well. 11 MR. SMITH: Let's take a break. 12 (A SHORT RECESS WAS TAKEN.) 13 Q. I'm a little confused. I've 14 been to pharmacies several times and gotten 15 medication from my pharmacy and had printouts 16 concerning the nature of the medication I have 17 been receiving, with contraindications, don't do 18 this with it, do this with it, don't take this 19 with it, you know, it's all right to take this. 20 Isn't that information here in the United States 21 that patients get? 22 A. Well, what you're describing 23 is what's referred to as a patient's instruction 24 sheet. That's different from prescribing Page 215 1 information. 2 Q. Now the patient instruction 3 sheet, I got that at the pharmacy, correct? 4 A. That's correct. 5 Q. All right. Do they have 6 patient instruction sheets here in Philadelphia? 7 A. The depends on the medication, 8 not all medications have patient instruction 9 sheets. 10 Q. Have you seen patient 11 instruction sheets in connection with medication? 12 A. Yes, I have. 13 Q. Giving patients information 14 with respect to how to take the medicine and 15 warning them and advising them concerning certain 16 propensities or properties of the medicine, 17 correct? 18 A. I've seen such documents on 19 drugs, yes. 20 Q. Would you have any problem 21 with this information that's related in the 22 German package insert being given to patients in 23 the United States in this patient instruction 24 sheet material? Page 216 1 A. Yes, I would. 2 Q. Why? 3 A. I feel it's the responsibility 4 of the physician prescribing the medication to 5 inform the patient about the medication, how it 6 works, what to expect, what side effects may 7 occur, what contraindications they need to be 8 aware of, and the things they need to look for 9 and report back to the physician about. I feel 10 very strongly that's the physician's 11 responsibility in prescribing a medication to a 12 patient. 13 Q. What would hurt if a patient 14 got this information, what would be a problem 15 with the patient getting this information? 16 A. My concern is that patients 17 need to understand the context in which the 18 warnings and contraindication are given, and that 19 can't be accomplished by handing one sheet of 20 paper or two sheets of paper to a patient, it 21 should occur within the confines of a discussion 22 between the physician and the patient that he's 23 treating. 24 Q. That's fine. If there is a Page 217 1 patient/physician discussion like that, would you 2 have any objection to, after that instruction, 3 that conversation between the patient and the 4 physician, the patient getting some material that 5 is of this nature? 6 A. The patient getting 7 information concerning their disease state, what 8 to expect in terms of response to treatment, is 9 completely appropriate, I think, yes. 10 Q. In other words you're saying 11 that the physician has the primary duty to advise 12 a patient of particular contraindications and 13 warnings and the effect of the medication, 14 correct? 15 A. That is correct. 16 Q. But you also agree that a 17 patient has the right to certain independent 18 information? 19 A. That is correct. 20 Q. Wouldn't you agree that 21 patients being well-informed is good medical 22 practice? 23 A. I would agree with that. 24 Q. Regardless of the mode by Page 218 1 which they're informed? 2 A. I don't necessarily agree with 3 that. 4 Q. All right. Well, if the 5 information is of scientific value and is 6 accurate? 7 A. And is provided by a health 8 care professional. 9 Q. All right. Or a 10 pharmaceutical firm or a pharmacy? 11 A. As I mentioned, is provided by 12 a health care professional. 13 Q. Do you include pharmaceutical 14 firms and pharmacies as health care 15 professionals, Doctor Wheadon? 16 A. A pharmacist providing that to 17 a patient is a health care professional. A 18 pharmaceutical firm is a large entity that has no 19 relationship with the patient. So a pharmacy 20 providing that, I'm in agreement with, a 21 pharmaceutical firm providing that, I have 22 difficulty with, there's no relationship, there's 23 no personal contact. 24 Q. Are you saying that a Page 219 1 pharmaceutical firm doesn't have a duty to the 2 public, in your opinion, to advise the public of 3 risk in connection with their products? 4 MR. FREEMAN: Are you talking about a 5 prescription drug? 6 MR. SMITH: Yes. 7 A. In my opinion, the 8 pharmaceutical firm has responsibility to inform 9 practicing health care professionals, and of 10 course, as always, the regulatory agency, about 11 information concerning their drugs, prescription 12 products. 13 Q. I'm not talking about health 14 care professionals or regulatory agencies, I'm 15 talking about the people who are going to put the 16 drugs in their body, the public? 17 A. I will repeat. The 18 responsibility lies between the pharmaceutical 19 firm and the physicians prescribing their 20 prescription products, and the regulatory agency. 21 The responsibility to inform patients lies with 22 the health care professional, he has the 23 relationship, he knows the patient, he knows the 24 medical history, and that is where that Page 220 1 information should be coming from. 2 Q. But you don't see any 3 responsibility of the manufacturer of the product 4 to advise the consumer of the product of the 5 nature of the product? 6 MR. FREEMAN: Objection, that's been 7 asked and answered about seven times. 8 A. I agree with counsel, I have 9 answered that question. 10 Q. Well, maybe I've forgotten it 11 or lost it somehow. Would you repeat your answer 12 for me? 13 MR. COLEMAN: I think you can have the 14 court reporter read back your question. 15 A. Would you read my answer, 16 please? 17 (THE COURT REPORTER READ BACK THE 18 REQUESTED TESTIMONY.) 19 Q. I guess maybe my confusion is 20 you mentioned the term pharmaceutical firm in the 21 first part of that answer, and then started 22 talking about the physician's and regulatory 23 responsibilities. Are you drawing a distinction 24 there in your answer? Page 221 1 A. I'm not sure I understand your 2 question. 3 Q. Well, then, without repeating 4 myself, do you feel that the manufacturer of the 5 drug has any responsibility to the patient, the 6 individual who's consuming the drug, to inform 7 the patient of any risk inherent in the drug? 8 MR. COLEMAN: That's the same 9 question. Ask another question, that's the same 10 question. 11 MR. FREEMAN: And I want to put this 12 objection on the record: In the first place, it 13 is a legal question, this witness is not 14 qualified as a legal expert. Legally the company 15 is not permitted to do that for reasons that the 16 witness has stated. 17 MR. COLEMAN: I think that's a 18 verbatim repeat of the question that we just had 19 read back and answered. Now I ask the court 20 reporter to read back the question. 21 MR. SMITH: Then I'll make the 22 objection that the answer was not responsive to 23 the question asked, and ask you to answer the 24 question -- Page 222 1 MR. COLEMAN: I think you have to ask 2 a different question because he thinks it was 3 responsive, and he's going to give you the same 4 answer because you gave him the same question. 5 If you don't think it's responsive, you better 6 ask another question. 7 MR. SMITH: All right, I'll try 8 another question. 9 Q. Do you believe that the public 10 has the right to know the risks inherent to 11 prescription medication? 12 MR. COLEMAN: That's the same 13 question. 14 MS. ZETTLER: No, it's not. 15 MR. FREEMAN: Objection, same legal 16 duty, the same -- it's a legal question. It 17 doesn't make any difference what this witness 18 believes or doesn't believe, because you can't do 19 it. 20 MS. ZETTLER: Gentlemen, that's simply 21 not true, it's simply not true, absolutely not 22 true. 23 MR. COLEMAN: Doctor, whether I think 24 it's the same question or not, I suppose is Page 223 1 irrelevant. If you see a difference in that 2 question from the one you answered before, then 3 you can answer that question. If you understand 4 it to be the same question, then tell Paul that 5 that's what you think. 6 A. I understand it to be the same 7 question. 8 Q. So your answer would be the 9 same? 10 A. It would be exactly the same, 11 yes. 12 Q. Regardless of who's 13 responsible for advising the public concerning 14 the risk inherent to a particular drug, does the 15 public have the right to know of the risk 16 inherent in a particular prescription medication? 17 A. The patient has the right to 18 be informed by his physician of the risks 19 inherent in taking a drug that that physician has 20 prescribed. 21 Q. Does the pharmaceutical 22 manufacturer have the responsibility to advise 23 the physician of the risks inherent to the 24 products they're prescribing to patients? Page 224 1 MR. FREEMAN: We'll stipulate that, we 2 do. 3 Q. I want an answer. 4 MR. COLEMAN: You can answer. 5 MR. FREEMAN: These are all legal 6 questions. 7 A. In the prescribing information 8 that's included with the medication, 9 pharmaceutical firms inform the physician of the 10 mechanism of action, the intended treatment of 11 the disease for which the drug is to be 12 prescribed, and the side effects, 13 contraindications, the warnings, the things the 14 physician needs to know in prescribing the drug. 15 Q. Do you believe that a 16 physician should be advised in connection with 17 Prozac that there was a study that indicated that 18 suicide attempts were observed more frequently on 19 Prozac as compared to Imipramine and placebo? 20 A. I'll repeat that there was not 21 a study. What you are reading from is, again, a 22 document that I had not seen before, so I cannot 23 offer an opinion beyond that. 24 Q. No, that's not what my Page 225 1 question was, that's not responsive to the 2 question I asked. 3 A. You can ask the question 4 again. 5 Q. I'll be glad to. Do you 6 believe that a physician should be advised by a 7 drug company that they conducted a study that 8 showed with respect to Prozac, that suicidal -- 9 suicide attempts were observed more frequently on 10 Prozac as compared to Imipramine versus placebo? 11 A. I'll repeat. I'm not aware of 12 a study that showed that Prozac had more suicide 13 attempts than Imipramine. 14 Q. If there were such a study -- 15 assume there were such a study -- 16 MR. FREEMAN: That's all too 17 hypothetical, Paul, let's move on to something 18 else. 19 Q. -- do you believe that the 20 pharmaceutical firm should advise the physician 21 of the existence of such study? 22 A. I refuse to answer such 23 conjecture. 24 Q. No, you don't have the right Page 226 1 to refuse to answer anything, Doctor Wheadon. 2 You're here under subpoena. We can have you 3 brought before a judge to answer that question. 4 A. I'm here under subpoena to 5 answer factually my knowledge concerning my 6 employment at Eli Lilly and Company, I'm not here 7 to offer opinion on conjecture. 8 Q. It's not conjecture. 9 A. It is conjecture. 10 Q. It says here, does it not, 11 that still not observed is the fact that suicide 12 attempts have been observed more frequently on 13 fluoxetine as compared to Imipramine? 14 A. And I mentioned to you I have 15 not seen a document, and please identify a 16 document number. 17 Q. Document number seven is the 18 exhibit we're speaking of. 19 A. As I mentioned before, I have 20 not seen document seven before. As I mentioned, 21 I'm not aware of the study referred to in 22 document seven. I cannot answer your question 23 beyond that. 24 Q. All right. I believe you Page 227 1 testified earlier that the data that you had seen 2 where Prozac was compared to comparitor drugs and 3 placebo, grouped Imipramine with other comparitor 4 drugs, is that right? 5 A. That's correct. 6 Q. And what you haven't seen is 7 any results of any study that compared 8 Imipramine, placebo and Prozac only. 9 A. That is correct. 10 Q. Now, assuming that there is 11 such a study, and I can give you -- its protocol 12 number twenty-seven, it was done before you came 13 to Lilly, but when you were at Lilly, you placed 14 a great reliance on all the studies that were 15 done, did you not, in the clinical trials in 16 drawing conclusions in connection with this drug? 17 A. That's correct. 18 Q. Now, my question is, if there 19 was such a study that indicated that there was a 20 higher frequency of suicide attempts on Prozac 21 versus placebo and Imipramine, should a physician 22 have that information? 23 MR. FREEMAN: Objection. That's been 24 asked and answered about five times. Page 228 1 MS. ZETTLER: I think he refused to 2 answer it, Joe, so it has not been. 3 A. As I stated before, I'm being 4 asked to comment and to answer factually. I'm 5 not aware of such a study, have no ability to 6 offer any answer to that question beyond that 7 statement. 8 Q. Assume that a study exists 9 that reflects that. Should a physician have a 10 right to be advised of that by the pharmaceutical 11 firm? 12 MR. FREEMAN: Asked and answered. 13 A. I repeat -- 14 MR. COLEMAN: You don't have to 15 repeat. If you think you answered the question, 16 tell him. 17 A. I answered the question time 18 and time again. 19 MS. ZETTLER: Certify the question. 20 (QUESTION CERTIFIED.) 21 Q. Is rash a risk inherent with 22 use of -- the use of Prozac? 23 A. Rash has been reported in 24 patients on Prozac. Page 229 1 Q. Are physicians advised of the 2 reports of rash occurring in patients using 3 Prozac? 4 A. Rash is listed in the 5 prescribing information as an adverse event seen 6 in clinical trials in patients on Prozac. 7 (PLAINTIFFS' EXHIBIT NO. 9 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Have you had an opportunity to 11 review Exhibit 9? 12 A. Yes, I have. 13 Q. Do you recall being at the 14 meeting at the Food and Drug Administration which 15 occurred on May 13, 1991? 16 A. Yes, I do. 17 Q. And do you recall that there 18 was discussions of a rechallenge study at that 19 time? 20 A. Yes, I do. 21 Q. And do you recall that Lilly 22 agreed to do a rechallenge study in May of 1991? 23 A. I do not recall Lilly agreeing 24 to do a rechallenge study. Page 230 1 Q. Do you agree with me, Doctor 2 Wheadon, that the first page of Exhibit 9 3 indicates, quote, at the FDA meeting, Lilly 4 agreed to do the following projects? 5 A. I agree that Doctor Kotsanos 6 offered the recollection that at the FDA meeting 7 Lilly agreed to do the following projects, I do 8 not recall there being an agreement at that 9 meeting. 10 Q. Do you recall there being a 11 disagreement? 12 A. I recall there being a 13 discussion, I do not recall there being an 14 agreement that a rechallenge study would be done. 15 Q. Number one says, proceed with 16 the rechallenge study, does it not? 17 A. The document in front of me 18 does have as number one proceed with the 19 rechallenge study. 20 Q. Under the second bullet point 21 it says, we agreed to have the rechallenge 22 protocol ready to go by September 1, 1991, 23 doesn't it? 24 A. The document in front of me Page 231 1 does say we agreed to have a rechallenge study 2 protocol ready to go. 3 Q. It also says and, quote, to 4 provide data after the first quarter, which would 5 provide information on six months of experience, 6 end quote, doesn't it? 7 A. That's what the document 8 reads. 9 Q. Do you disagree that Doctor 10 Kotsanos accurately recorded what Lilly agreed to 11 do? 12 A. I do not recall agreeing to a 13 rechallenge protocol, per se. 14 Q. Per se? 15 A. As I mentioned, there was 16 discussion of a rechallenge study, there was 17 discussion of considerations of problems with the 18 rechallenge study, one of which is noted on page 19 two by Doctor Leber himself. I do not recall an 20 agreement to proceed with the rechallenge 21 protocol. 22 Q. Do you recall that it was 23 agreed that the rechallenge protocol would be 24 ready to go by September 1, 1991? Page 232 1 A. Again, I do not recall a 2 specific date being proffered as the date at 3 which the rechallenge protocol would be ready to 4 go. 5 Q. Do you think Doctor Kotsanos 6 is inaccurate in giving that particular data? 7 A. I repeat, I do not recall. 8 Doctor Kotsanos is not necessarily inaccurate, I 9 do not recall it. 10 Q. He wrote it down, didn't he? 11 A. He wrote it in this memo. 12 Q. Did you write a memo 13 concerning your recollections of that meeting? 14 A. I did not write a memo 15 concerning that meeting. 16 Q. Did you write a memo to any of 17 these individuals listed on this exhibit saying I 18 don't recall that we agreed to September 1, 1991 19 as being the date we would have the rechallenge 20 protocol ready to go? 21 A. I do not recall writing a memo 22 concerning that specific date. 23 Q. You didn't voice any 24 disagreement or inaccuracies to anybody in Page 233 1 writing concerning that September 1, 1991 date, 2 did you? 3 A. I did not recall voicing 4 disagreement in writing to anyone. 5 Q. Did you voice agreement -- 6 disagreement in person, orally, to anyone? 7 A. I cannot recall agreeing or 8 disagreeing with September 1, 1991 as the date 9 for the rechallenge protocol. 10 Q. The document says that you 11 would provide data after the first quarter, which 12 would provide information on six months of 13 experience, doesn't it? 14 A. That is what the document 15 reads. 16 Q. None of that was ever done, 17 was it? 18 A. I do not recall at the time I 19 left Lilly that the rechallenge protocol had been 20 initiated or agreed upon. 21 Q. Therefore there was never six 22 months of experience certainly, was there? 23 A. If there was no protocol, 24 there could not be six months of experience. Page 234 1 Q. There was a protocol, wasn't 2 there, Doctor? 3 A. As I mentioned, I do not 4 recall there being agreement on a rechallenge 5 protocol at the time I left Lilly in February of 6 1992. 7 Q. Well, you recall a protocol 8 being submitted to the Food and Drug 9 Administration, don't you? 10 A. As I mentioned, I do not 11 recall there being agreement on a rechallenge 12 protocol. 13 Q. That's not what I asked you, I 14 asked you do you recall a protocol being 15 submitted to the Food and Drug Administration? 16 A. I do not recall a protocol 17 being submitted to the Food and Drug 18 Administration. 19 (PLAINTIFFS' EXHIBIT NO. 10 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 MR. SMITH: Look at Exhibit No. 10 and 23 see if that doesn't help your recollection, 24 Doctor Wheadon. Page 235 1 Q. Exhibit No. 10 is a document 2 three months prior to Exhibit No. 9, isn't it? 3 A. Roughly, yes. 4 Q. It's a document signed by 5 Doctor Max Talbott, director of medical 6 regulatory affairs, isn't it? 7 A. No, it is signed by Robert 8 Zerbe for Max Talbott. 9 Q. And it's sent to the Food and 10 Drug Administration, isn't it? 11 A. That's correct. 12 Q. And it's entitled IND 12, 13 comma, 274, Prozac, isn't it? 14 A. The reference is that the 15 letter's concerning IND 12,274 Prozac. 16 Q. It says, we are submitting a 17 draft protocol entitled fluoxetine, Imipramine, 18 placebo rechallenge study in patients who 19 developed suicidal ideation while under 20 treatment, doesn't it? 21 A. The letter does say that. 22 Q. And there is a rechallenge 23 protocol attached to this letter, isn't it? 24 A. There is a protocol attached Page 236 1 to the letter entitled fluoxetine, Imipramine, 2 placebo rechallenge study in patients who 3 developed suicide ideation while under treatment, 4 also with the designation "draft." 5 Q. So a rechallenge protocol had 6 been submitted to the Food and Drug 7 Administration, hadn't it? 8 A. My statement was I did not 9 recall submitting a protocol -- rechallenge 10 protocol to the Food and Drug Administration. 11 Q. I understand that. That 12 wasn't your job, was it -- 13 A. I don't understand your 14 question. 15 Q. -- to submit protocols to the 16 Food and Drug Administration? 17 A. No, it was not my job. 18 Q. It was Doctor Talbott's job, 19 though, wasn't it? 20 A. Doctor Talbott was head of the 21 regulatory group. 22 Q. And he was the individual that 23 submitted protocols to the Food and Drug 24 Administration, wasn't he? Page 237 1 A. Protocols were submitted to 2 the IND to the regulatory group. 3 Q. To the Food and Drug 4 Administration? 5 A. To the Food and Drug 6 Administration. 7 Q. And a draft protocol was 8 submitted to the Food and Drug Administration, 9 wasn't it? 10 A. That is correct. 11 Q. For consideration by the Food 12 and Drug Administration? 13 A. It appears to be that way 14 based on what you've shown me. 15 Q. And you weren't aware of that 16 when I asked you earlier about the rechallenge 17 protocol, were you? 18 A. As I stated, I did not recall 19 submitting a rechallenge protocol to the Food and 20 Drug Administration. 21 Q. But in fact one had been 22 submitted to the Food and Drug Administration? 23 A. In fact a draft protocol was 24 submitted, along with an introductory overview of Page 238 1 other alternative study designs as outlined in 2 the letter. 3 Q. Right. Then two and a half 4 months later you have this meeting, correct, at 5 the Food and Drug Administration? 6 A. That's correct. 7 Q. You were there for that 8 meeting. 9 A. That's correct. 10 Q. That the document, as 11 reflected by Exhibit 9, authored by Doctor 12 Kotsanos, says that Lilly agreed to proceed with 13 the rechallenge study. 14 A. I will repeat that I do not 15 recall agreeing to proceed with the rechallenge 16 protocol. 17 Q. Well, it was going to be ready 18 to go by September 1, 1991, according to Doctor 19 Kotsanos. 20 MR. COLEMAN: Paul, he said he doesn't 21 recall it happening, that's not saying it didn't 22 happen. I think my only job here is to not let 23 the witness be harrassed, and I think you asked 24 that question about eight times. He didn't say Page 239 1 he disagrees, he just says he doesn't remember it 2 happening. 3 MR. SMITH: I get the impression from 4 the witness that he doesn't agree -- that he 5 disagrees that Lilly agreed to the rechallenge 6 protocol. 7 MR. COLEMAN: His testimony was I 8 don't remember an agreement, that was his 9 testimony. 10 Q. Do you agree -- do you 11 remember that there was going to be something 12 done by Lilly with respect to a rechallenge study 13 discussed at the meeting with the FDA on May 13, 14 1991? 15 A. I recall discussions of a 16 rechallenge protocol, I recall discussions 17 concerning the problems with the rechallenge 18 protocol voiced both by Lilly and by the FDA. 19 Q. All right. What else do you 20 recall, is that it? 21 A. That is a very vague question, 22 you have to be more specific than that. 23 Q. Do you recall that there would 24 be a modified scale for suicidal ideation Page 240 1 included in ongoing and planned United States and 2 United Kingdom clinical trials? 3 A. I recall discussion concerning 4 the modified suicide ideation scale for inclusion 5 in ongoing trials. 6 Q. Do you have any explanation as 7 to why there wasn't a rechallenge protocol ready 8 to go by September 1, 1991? 9 A. As I have already expressed, 10 there were considerations, both on the point of 11 Lilly and the FDA, about the problems with a 12 rechallenge protocol. 13 Q. Tell me what your recollection 14 is of what the problems were discussed concerning 15 the problems of a rechallenge protocol? 16 A. One of the considerations is 17 the inherent bias. A patient has already 18 expressed obsession with suicidal thought, it 19 could be inherent bias in rechallenging that 20 patient. Another issue is an ethical concern. A 21 patient already having experienced this obsessive 22 suicidal drive, to rechallenge that patient, it 23 requires very specific ethical consideration. 24 Those are two prime considerations in looking at Page 241 1 the rechallenge protocol. 2 Q. What else? 3 A. In addition, the time frame 4 required to carry it out in terms of, again, the 5 number of patients that would have to be 6 canvassed to find patients who would -- who would 7 express this phenomena, this obsessive drive 8 towards suicide. So you would have to canvass 9 thousands of patients to cull down to those 10 patients that have it in order for them to be 11 rechallenged. So it still requires a large 12 number of patients, a large amount of time to 13 even get to the point where you could do the 14 rechallenge protocol. 15 Q. So what, why was that a 16 problem? 17 A. Certainly there was an issue 18 in terms of, both for the FDA and Lilly, getting 19 an answer in as rapidly a time frame as possible. 20 Q. Why would you want an answer 21 in as rapidly a time frame as possible? 22 A. Because this was a very 23 important issue for the FDA, for Lilly. 24 Q. How about for the people that Page 242 1 were taking the drug? 2 A. We are speaking of Lilly and 3 the FDA right now. A very important issue, very 4 important to address the issue in as rapid a time 5 frame as possible. A prospective study, as we 6 have discussed, could encompass thousands of 7 patients in a very long time frame. So those 8 were considerations in looking at the rechallenge 9 protocol. 10 Q. Wait. Couldn't you have a 11 prospective study on the issue of suicidality as 12 one study, and a rechallenge study as another 13 study? 14 A. In order to identify the 15 patients to rechallenge, you would have to 16 prospectively treat them with Prozac, 17 Desipramine, what have you, to find those 18 patients that expressed the phenomena. 19 Q. Well, you already had some 20 patients that had expressed that phenomena. 21 A. Not in a controlled fashion. 22 Q. Some had been found in a 23 controlled fashion, hadn't they? 24 A. When you say some had been Page 243 1 found in a controlled fashion, what do you mean? 2 Q. People had expressed suicidal 3 ideation while on the Prozac clinical trials, had 4 they not? 5 A. However, they had not 6 expressed the sort of obsessive drive as 7 described by Doctor Teicher, that is the salient 8 issue. 9 Q. Okay. Your understanding was 10 is what Lilly was looking for was something that 11 was being described by Doctor Teicher as some 12 obsessive drive to commit suicide? 13 A. If you will recall, in fact in 14 document nine, second page, the FDA requested 15 that the questionnaire, speaking of the MSSRI, 16 the modified suicide scale, be reviewed by other 17 independent investigators and experts, in 18 particular they asked if Doctor Teicher had 19 reviewed the scale or if we could share with 20 Doctor John Cole the second author, again because 21 we are looking at specifically the issue raised 22 by Doctor Teicher in his article, the obsessive 23 drive towards suicidal ideation. 24 Q. I don't know about that, Page 244 1 because look on page two of Doctor Kotsanos' 2 memo, it says, quote, Doctor Leber made mentioned 3 that it may be worthwhile to determine what the 4 risk incidence is of the development of these 5 symptoms in garden variety patients treated for 6 the first time with fluoxetine versus other 7 agents. Do you see that? 8 A. I do see that. What is your 9 point? 10 Q. My point is, it doesn't appear 11 to me that Doctor Leber is looking for people who 12 have obsessive compulsion towards suicide. And I 13 don't see it in the protocol that that's what is 14 being sought. 15 A. I need to read through the 16 protocol specifically since you're making that 17 statement. 18 Q. Sure. 19 A. If you look at inclusion 20 criteria on page two of the draft protocol, 21 section two of the inclusion criteria, during 22 treatment with either fluoxetine, a tricyclic 23 antidepressant or Maprotiline, the patient 24 developed in the clinical opinion of the treating Page 245 1 psychiatrist substantial suicide ideation with or 2 without an act characterized by all the following 3 features: A, a quantum, slash, extreme increase 4 in severity; B, method -- contemplated method or 5 methods contempted for violent and/or active; C, 6 considered obsessive and/or ego dystonic. 7 Q. Okay. And is it your judgment 8 that that's calling for the extreme suicidal 9 ideation mentioned by Teicher? 10 A. It's my judgment that this is 11 attempting to recreate the extreme suicidal 12 ideation described by Doctor Teicher his case 13 reports. 14 Q. So is it then that you were 15 only looking for a specific type of patient who 16 might become suicidal while on Prozac? 17 A. No, I do not agree with your 18 statement. 19 Q. Well, then, I don't understand 20 why you're saying that we were looking for the 21 same type of patients described by Teicher. 22 A. The issue, again, was that 23 Doctor Teicher had described a phenomena that he 24 felt was distinct from suicidal ideation in the Page 246 1 majority of patients with depression that he had 2 treated. 3 Q. Uh-huh. 4 A. Something very different. 5 Q. Uh-huh. 6 A. A very different degree, a 7 very different variety in terms of this type of 8 suicidal ideation. As outlined in this protocol, 9 the attempt by inclusion criteria, two, was to 10 try and recreate the phenomena that Doctor 11 Teicher was prescribing in terms of patients that 12 were included in this rechallenge protocol. 13 Q. All right. So you weren't 14 looking for patients who just experienced 15 increased suicidal ideation? 16 A. Not as outlined in this draft 17 rechallenge protocol. 18 Q. And you weren't looking at 19 patients who had just, if there's such a term, 20 had some type of suicide attempt? 21 A. Again, the draft challenge 22 protocol in front of me is focusing specifically 23 on suicidal ideation, not acts or attempts, if 24 you will. Page 247 1 Q. It says with or without an 2 act. 3 A. Would you care to point out 4 what you're focusing on? 5 Q. Under inclusion criteria, 6 point two, it says in the clinical opinion of the 7 treating psychiatrist, substantial suicidal 8 ideation with or without an act. 9 A. Right. And my statement was 10 that the protocol was not focusing specifically 11 on suicidal acts. 12 Q. But it could include those who 13 had acted on that ideation? 14 A. As the draft protocol reads, 15 it could include someone who had had a suicide 16 attempt, that's correct. 17 Q. And in fact there would, I 18 guess, have to be some attempt because it said 19 methods contemplated were violent and/or active, 20 it says contemplated. 21 A. Right. 22 Q. It doesn't mean it necessarily 23 had to have occurred? 24 A. That's correct. Page 248 1 Q. What is ego dystonic? 2 A. Ego dystonic means that it is 3 alien to a person's basic psychological makeup. 4 So it's almost as if against their own best 5 wishes, they have these thoughts, they can't 6 shake these thoughts, so it's ego dystonic. An 7 example, perhaps, might be of, say, someone who 8 can't stop smoking. They know they shouldn't 9 smoke, they don't want to smoke, the family hates 10 their smoking, and they can't stop themselves. 11 You could say that's ego dystonic. 12 (DISCUSSION OFF THE RECORD.) 13 Q. So what if a patient says I 14 just felt like I should do it, that it would be 15 best for me and everybody concerned if I 16 committed suicide, would that mean he was not ego 17 dystonic? 18 A. That in and of itself wouldn't 19 be described as ego dystonic. Whereas a patient 20 who said I really don't want to kill myself, but 21 I can't shake this notion of me hanging from a 22 noose, that could be described as ego dystonic. 23 Q. All right. What other 24 problems were there inherent to a rechallenge Page 249 1 study? You've identified client bias, ethical 2 considerations, and the time frame, number of 3 patients that would have to be looked at. 4 A. Those are the primary 5 problems. 6 Q. Was the rechallenge study not 7 done because of those problems? 8 A. As I mentioned, at the time 9 that I left Lilly there had not been a decision 10 that the rechallenge study was not going to be 11 done or going to be done, it was still under 12 consideration. 13 Q. So you don't know that any of 14 these problems proved to be of such in nature 15 that they prevented Lilly from doing this study? 16 A. Correct, I do not know. 17 Q. Did you express any opinions 18 in this meeting that you recall, that's mentioned 19 in Exhibit 9, on May 13th? 20 A. I cannot recall expressing 21 personal opinions in the meeting on May 13th, 22 1991 at the FDA. 23 Q. The FDA at that time was 24 suggesting a more sophisticated scale for Page 250 1 suicidal ideation than had been used by Lilly up 2 to that time, weren't they? 3 A. When you say a more 4 sophisticated scale, what do you mean? 5 Q. Well, you had been using the 6 Ham-D, and it was the FDA -- and it says the FDA 7 was interested in including the MSSI-R modified 8 scale for suicidal ideation in clinical trials, 9 correct? 10 A. That is written in the 11 document, yes. 12 Q. Do you recall that it was 13 mentioned that the modified scale for suicidal 14 ideation be included in ongoing trials? 15 A. I do recall discussion on 16 that, yes. 17 Q. And was that done? 18 A. I do recall the MSSI-R being 19 included in some clinical trials, yes. 20 Q. Which ones? 21 A. I do not recall specifically 22 which trials. 23 Q. How about in ones that you 24 were the medical monitor on? Page 251 1 A. They were not in the trials in 2 which I was a medical monitor. 3 Q. Why? 4 A. Well, if you recall, this is a 5 discussion point in late 1991, and I left Lilly 6 early 1992. So the trials I was working on were 7 in the process either of completing or having 8 been completed. 9 Q. It mentions here a descriptive 10 study of patients reported to develop intense 11 violent suicidal thoughts. What is a descriptive 12 study that they're mentioning there? 13 A. The -- a descriptive study in 14 general, and in this case, is looking very in 15 depth at patients that were reported to have this 16 sort of adverse event. 17 Q. It discusses a pilot study 18 might be worth pursuing in this connection. Do 19 you know if a pilot study was ever done? 20 A. I do not recall a pilot study, 21 in terms of descriptively studying the patients, 22 had been done by the time I left Lilly. 23 Q. There was no prospective study 24 done while you were at Lilly either -- Page 252 1 A. There was no prospective 2 study. 3 Q. -- examining the issue of 4 Prozac and suicidality? 5 A. A prospective study had not 6 been initiated examining the issue of Prozac and 7 suicidality by the time I left Lilly. 8 Q. I mean there hadn't been any 9 protocols drafted other than this rechallenge 10 protocol? 11 A. I do not recall protocols 12 drafted for a prospective study. 13 Q. Are you -- do you know Doctor 14 Stuart Montgomery or of Doctor Stuart Montgomery? 15 A. I know Doctor Stuart 16 Montgomery, yes. 17 Q. Was he one of the foreign 18 consultants that you met with in 1990? 19 A. I do not recall meeting with 20 Doctor Montgomery during the course of that trip, 21 no. 22 Q. Tell me about your meetings 23 with Doctor Montgomery itself. 24 A. I've interacted with Doctor Page 253 1 Montgomery in a number of symposiums where he had 2 been giving a talk and I may have been giving a 3 talk. I have interacted with Doctor Montgomery 4 in the course of various psychiatric meetings, 5 APA, American Psychiatric Association, the 6 American College of Neuropsychopharmacology. 7 It's been just continuing associations through 8 meetings and what have you. 9 Q. What is your understanding of 10 what Doctor Montgomery's expertise is in 11 psychiatry? 12 A. Doctor Montgomery is an 13 academically affiliated psychiatrist in the UK 14 who has done a number of clinical trials in 15 depression as well as other disorders, of 16 psychopharmacologic agents. 17 Q. Do you know if he's done any 18 clinical trials using Prozac? 19 A. I'm aware that Doctor 20 Montgomery has done trials in depression using 21 Prozac. 22 Q. Do you know when those trials 23 began and/or ended? 24 A. I cannot recall the exact Page 254 1 dates of beginning or ending of those trials. 2 Q. Approximately? 3 A. I can't even give you 4 approximate dates. 5 Q. Were they ongoing or had they 6 been completed while you were at Lilly? 7 A. I think Doctor Montgomery's 8 were ongoing at the time I left Lilly. 9 Q. And has he advised you what 10 the results of his trials were since you've seen 11 him in these meetings? 12 A. The results of Doctor 13 Montgomery's trials on Prozac were proprietary 14 information, and as no longer an employee of 15 Lilly, I was not informed of those results. 16 Q. Okay. So is the answer to my 17 question no, he hasn't advised me? 18 A. The answer to your question is 19 no. 20 Q. But it's your understanding 21 that Doctor Montgomery was hired to perform 22 clinical trials on depressed individuals and to 23 administer Prozac to those individuals? 24 A. Doctor Montgomery performed as Page 255 1 an investigator for Lilly, yes. 2 Q. And did he do any surveillance 3 studies in addition to those depression studies? 4 A. I cannot recall any 5 surveillance studies that Doctor Montgomery's 6 done. 7 Q. Are you aware that Doctor 8 Montgomery has done a study specifically 9 examining the relationship of Prozac and suicide? 10 A. I'm aware that at the time I 11 left Lilly, Doctor Montgomery was involved in a 12 study looking at Prozac in patients, not just 13 depressed patients, of patients with suicidal 14 behavior. 15 Q. All right. And how many 16 patients did he have on that study? 17 A. I'm not aware of anymore 18 specifics on that study other than the fact that 19 it was ongoing. 20 Q. When you say ongoing, does it 21 mean that at the time you left, there were 22 patients still participating in the clinical 23 trials taking Prozac? 24 A. I was not aware that the study Page 256 1 had terminated at the time I left Lilly. 2 Q. No, my question is, were the 3 trials still ongoing where patients were still 4 taking the medication? 5 A. As I mentioned, I was not 6 aware that the trial had terminated. In the 7 carrying out of clinical trial, enrollment can be 8 sporadic. So whether or not patients were taking 9 Prozac at the exact time I left Lilly, I have no 10 idea, but the trial had not been terminated. 11 Q. Had you seen any preliminary 12 results of the clinical trials -- 13 A. At the time I left Lilly? 14 Q. -- on suicidality? 15 A. I had not seen any preliminary 16 results. 17 Q. Would this have been a trial 18 you would have been a global monitor or global 19 physician overseeing? 20 A. If I recall, this trial was 21 being carried out through the UK medical 22 affiliate solely, and as such was not a trial 23 that I was responsible for. 24 Q. Has Doctor Montgomery advised Page 257 1 you in any respect, any results, any findings, 2 any impressions he has concerning the status of 3 that trial? 4 A. No, he's not. 5 Q. Have you asked? 6 A. No, I have not. 7 Q. Were there suicide attempts on 8 that study? 9 A. At the time I left Lilly, I 10 had not seen data concerning that study. 11 Q. Is the answer to my question, 12 I don't know? 13 A. The answer to your question is 14 I do not know, yes. 15 Q. Whether you had seen any data, 16 had anybody advised you, had you heard orally, 17 tangentially, in any way, that there had been 18 individuals who had attempted suicide on Doctor 19 Montgomery's suicide study? 20 A. Again, I do not recall 21 specifically that I had been informed that there 22 had been suicides in Doctor Montgomery's study 23 specifically. 24 Q. Or suicide attempts? Page 258 1 A. Or suicide attempts. 2 Q. Well, had you been advised 3 generally that there were such an instance? 4 A. I do not recall in Doctor 5 Montgomery's study -- in terms of Doctor 6 Montgomery's study, of being informed of suicides 7 in that study, attempts. 8 Q. Was that an inpatient or 9 outpatient study? 10 A. I do not recall the specifics. 11 Q. Was it a study that was being 12 done at one site or at multiple sites? 13 A. Again, I do not recall 14 specifics of the study. 15 Q. And you left in February of 16 1992, and that study had not been completed? 17 A. Not that I can recall. 18 Q. Do you recall Doctor 19 Montgomery doing other studies in addition to the 20 suicide study? 21 A. As I mentioned, Doctor 22 Montgomery has been an investigator in a number 23 of disorders. 24 Q. I understand that, but do you Page 259 1 recall that he had done other studies for Lilly 2 on Prozac? 3 A. Yes, I do recall that Doctor 4 Montgomery has done other studies for Lilly on 5 Prozac. 6 Q. In depression? 7 A. In depression and other 8 disorders. 9 Q. What other disorders? 10 A. I think Doctor Montgomery was 11 also involved in studies on obsessive compulsive 12 disorder. 13 Q. While she's looking for this 14 document, as an aside do you recall, Doctor 15 Wheadon, discussions with the FDA in reducing the 16 dosage of Prozac? 17 A. No, I do not recall 18 discussions with the FDA about reducing the 19 dosage of Prozac. 20 Q. Do you recall that the members 21 of the FDA asked if you were planning or if Lilly 22 was planning to develop a ten milligram dose? 23 A. I do recall discussions 24 concerning a ten milligram dosage form. Page 260 1 Q. That would be a reduced dosage 2 over that twenty milligram dosage that had been 3 provided in the pulvule, wouldn't it? 4 A. That would be a reduced dosage 5 form compared to the twenty milligram capsule. 6 Q. All right. What is the 7 difference? 8 A. The difference is your 9 original question is do I recall there being 10 discussions with the FDA about reducing the dose 11 of Prozac. When you say the dose, I think you're 12 saying the dose to treat depression, that's how I 13 read that question. 14 Q. I'm talking about the number 15 of milligrams that is contained in the pill that 16 the patient puts in their mouth. 17 A. And as I stated, I recall 18 discussions concerning the developing of a ten 19 milligram formulation, ten milligram dosage 20 formulation. 21 Q. Which would, in effect, be 22 less medicine than in the twenty milligram form, 23 correct? 24 A. In terms of the formulation, Page 261 1 yes. 2 Q. Why was the FDA inquiring as 3 to developing a ten milligram dose? 4 A. I'm not -- I do not recall why 5 the FDA was asking about the ten milligram dose. 6 Q. Did it have to do at all with 7 reducing side effects? 8 A. As I mentioned, I do not 9 recall why the FDA was asking about the ten 10 milligram dosage form. 11 Q. You just don't have any 12 recollection. You recall it being mentioned, but 13 you don't have any idea why it was being talked 14 about? 15 A. As the document reads, second 16 page, bottom of the page, the FDA mentioned three 17 more items. These items included, one, they 18 asked if we were planning to develop a ten 19 milligram dose, period. As indicated in the 20 document, all I recall in conjunction with what's 21 recollected in this document is that the FDA 22 asked about the ten milligram dosage formulation, 23 I do not recall why they asked about it. 24 Q. Did you ask anybody there, Page 262 1 wait a minute, why does the FDA want a ten 2 milligram or why are they asking us about a ten 3 milligram dose? 4 A. No, I did not ask. 5 Q. Have you got any opinion, 6 Doctor, as to why they were asking about a ten 7 milligram dose? 8 A. I cannot offer an opinion why 9 the regulatory agency would ask that question. 10 Q. Now a ten milligram dose is 11 being manufactured by Lilly, did you know that? 12 A. Yes, I did know that. 13 Q. Do you have an opinion as to 14 why Lilly is making a ten milligram dose now? 15 A. Lilly is manufacturing a ten 16 milligram dose for use in patients such as the 17 elderly patient where concomitant medical 18 illnesses may require a lower than twenty 19 milligram dose. 20 Q. How did you know that? 21 A. At the time I was at Lilly 22 there was discussion concerning a ten milligram 23 dose for those populations. 24 Q. Okay. And is that the only Page 263 1 reason that there was going to be a ten milligram 2 dose? 3 A. That's the only reason that I 4 recall that there would be a ten milligram dosage 5 formulation that was introduced. 6 Q. Were you aware that there was 7 a lot or that there was -- whether a lot was the 8 right term, but that there was some interest by 9 psychiatrists and by gurus that Lilly manufacture 10 a pill that had less dosage? 11 A. I was aware that there was 12 some interest in a lower than twenty milligram 13 dosage formulation for use in elderly patients 14 with concomitant medical illnesses and other 15 situations such as that. 16 Q. What about well people, like 17 me and you, except we're depressed? 18 MR. FREEMAN: Don't put you in that as 19 being well. 20 MR. SMITH: I'm just ego dystonic. 21 A. I was not aware of discussions 22 concerning -- or requests on the part of 23 psychiatrists for the use of a ten milligram dose 24 in, quote, well, depressed people. Page 264 1 Q. You know that ten milligram 2 can be efficacious in many individuals? 3 A. I do not know that ten 4 milligram can be efficacious in many individuals, 5 I do not know that. 6 Q. Okay. 7 MR. SMITH: Let's take a break. 8 (A SHORT RECESS WAS TAKEN.) 9 Q. Doctor Wheadon, are you 10 familiar with an article written or a study done 11 by Doctor Gary Tollefson concerning treatment 12 related suicidality? 13 A. I'm not familiar with a study 14 done by Doctor Tollefson entitled treatment 15 related suicidality. 16 Q. Are you familiar with a 17 placebo controlled double-blind trial with 18 respect to treatment related suicidality done by 19 Doctor Tollefson? 20 A. I'm not aware of a trial done 21 by Doctor Tollefson concerning treatment related 22 suicidality. 23 Q. Are you aware of any work or 24 any study or any research done by Doctor Page 265 1 Tollefson where he would have used or analyzed a 2 placebo controlled double-blind analysis? 3 A. Not to play wordsmith, but I'm 4 aware that Doctor Tollefson has published data 5 concerning the issue of treatment related or 6 treatment emergent suicidality, I'm not aware 7 that Doctor Tollefson has carried out any trials 8 concerning treatment emergent suicidality. 9 Q. I want to mark this as an 10 exhibit, but I want to show it to you, Doctor 11 Wheadon. This was a document that was submitted 12 by Lilly that mentions on the left side of the 13 page this study or this trial. 14 MR. FREEMAN: PZ two two five oh three 15 five nine. 16 A. And your reference was to the 17 left side of the page? 18 Q. Yes, sir. 19 A. And your question is? 20 Q. Are you familiar with that 21 work described on that page? 22 A. I have seen the abstract 23 you've handed me concerning data that Doctor 24 Tollefson discussed in his abstract. Again, I'm Page 266 1 not aware that Doctor Tollefson carried out a 2 trial in looking at treatment emergent 3 suicidality. 4 Q. Is it your understanding that 5 he reviewed some trials to form the basis of this -- 6 what did he do, write an article on it or 7 something? That's part of my confusion, I can't 8 tell whether there was a trial done, an article 9 written or a study done. 10 A. I have to agree with you that 11 from what you've given me in this abstract, I 12 cannot say what -- from what data was generated. 13 Q. All right. Down at the bottom 14 of the page, it says Clinical Research, volume 15 something, page something, doesn't it? 16 A. It reads Clinical Research, 17 volume thirty-nine, number three, 1991. 18 Q. Do you know what that has 19 reference to? 20 A. I'm assuming that Clinical 21 Research refers to a journal or supplement of 22 some sort. But again, it's not something that 23 I'm familiar with. 24 Q. In all of your medical Page 267 1 training and in your work in the medical field, 2 have you ever seen a scientific publication 3 called, quote, Clinical Research, end quote? 4 A. I cannot recall specifically a 5 publication entitled Clinical Research, no. 6 Q. Have you ever talked with 7 Doctor Tollefson about that particular matter? 8 A. That particular matter? 9 Q. That is discussed in that 10 abstract. 11 A. I have not talked with Doctor 12 Tollefson specifically about the two hundred 13 twenty-six patients discussed in this abstract, 14 no. 15 Q. You just can't give us any 16 assistance over and above what's written there? 17 A. I cannot give you more 18 assistance than that. 19 Q. It looks like that's a report 20 of a clinical trial, doesn't it? 21 A. Not necessarily. 22 Q. Why? 23 A. Because it reads we 24 investigated two hundred and twenty-six patients Page 268 1 who either received placebo or one of several 2 distinctly different antidepressant agents. So 3 it could be a retrospective review of cases, I 4 just -- I have no idea where it's coming from 5 beyond what I've told you. 6 Q. But that appears to be some 7 abstract of some more lengthy article, doesn't 8 it, or does it? 9 A. All I can say is that it 10 appears to be an abstract. 11 Q. It's in abstract form? 12 A. Right, exactly. 13 Q. We know that the -- on the 14 right-hand side of the page, fluoxetine not 15 associated with violent behavior in controlled 16 clinical trials, by Doctor Heiligenstein, 17 mentioned on the right-hand side, is a 18 retrospective study, it wasn't a separate 19 clinical trial. 20 A. That's correct. 21 Q. You're familiar with that 22 particular study, or are you? 23 A. I'm familiar with those 24 analyses. Page 269 1 Q. But you're not familiar with 2 the analysis done by Doctor Tollefson? 3 A. I'm not familiar with the 4 analyses designated in this abstract by Doctor 5 Tollefson. 6 Q. And again, for the record -- 7 MR. SMITH: Why don't we make a copy 8 of this and go ahead and attach this as an 9 exhibit. Do you want me to wait on you? 10 MR. COLEMAN: No, as long as you don't 11 ask any bad questions, go ahead. 12 (DISCUSSION OFF THE RECORD.) 13 (PLAINTIFFS' EXHIBITS 11 AND 12 14 WERE MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 Q. Doctor, we now marked -- or 17 the court reporter has now marked Exhibit 11, 18 this document we talked about containing the two 19 abstracts, okay? 20 A. That's fine. 21 MR. COLEMAN: Is it your practice to 22 attach these exhibits to the depositions? 23 Q. We've also marked Exhibit 12 24 that we would like for you to take a look at. Page 270 1 (WITNESS REVIEWS DOCUMENT.) 2 Q. Exhibit 13 is a document dated 3 June 13, 1988, correct? 4 A. That's correct. 5 Q. It's authored by Doctor Leigh 6 Thompson, correct? 7 A. That is correct. 8 Q. What was Doctor Thompson's 9 position in June of 1988? 10 A. If I recall correctly, it was 11 either executive director or vice president, I 12 can't be sure which one. 13 Q. Of what? 14 A. Of Lilly Research 15 Laboratories, medical group. 16 Q. This is 12. When I said 13 17 earlier, I meant 12. Exhibit 12 on the first 18 page, second paragraph, says there is tremendous 19 pressure from gurus and practicing psychiatrists 20 to make ten milligram or even five milligram 21 available. They are wrong that twenty milligram 22 is excessive from the safety data we have, but 23 they would not lose appreciable efficacy at ten 24 milligram, correct? Page 271 1 A. That's what the document 2 reads, yes. 3 Q. Do you agree that there was -- 4 or were you aware of pressure from gurus and 5 practicing psychiatrists that Lilly should make 6 ten milligrams of Prozac available? 7 A. I was not aware of pressure 8 from gurus or practicing psychiatrists, as you 9 say. As I mentioned -- 10 Q. Do you call them gurus or 11 gurus? 12 MR. COLEMAN: Gurus, the accent on the 13 ooh. 14 A. As I mentioned, I was aware 15 that clinicians asked about the availability of a 16 ten milligram dose. 17 Q. Do you agree that with Doctor 18 Thompson's assessment that twenty milligrams 19 would not lose -- that ten milligrams would not 20 lose appreciable efficacy in -- 21 A. I do not agree with that 22 statement on Doctor Thompson's part. 23 Q. Why? 24 A. Because it has not been Page 272 1 tested. 2 Q. You're not aware of clinical 3 trials testing the efficacy at ten milligrams in 4 depressed individuals? 5 A. I'm not aware of clinical 6 trials testing the efficacy of ten milligrams it 7 depressed individuals. 8 (PLAINTIFFS' EXHIBIT NO. 13 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.). 11 Q. Exhibit 13 is a document dated 12 July 7, 1988 authored by Doctor Gary Tauscher 13 A. Mister Tauscher is not a 14 doctor. 15 Q. Mister, that's right. I get 16 Tauscher and Tollefson confused. That document 17 indicates that there was input from the CNS 18 medical team, correct? 19 A. That is what the document 20 states, yes. 21 Q. You were part of the CNS 22 medical team, were you not? 23 A. That is correct. 24 Q. On July 7, 1988? Page 273 1 A. That is correct. 2 Q. It says all three physicians 3 have received requests for a lower dose from a 4 broad range of psychiatrists, does it not? 5 A. That's correct. 6 Q. Were you one of the three 7 physicians mentioned here? 8 A. I'm assuming I'm among the 9 three physicians, although I'm not specifically 10 named. 11 Q. Do you recall receiving 12 requests for a lower dosage of Prozac? 13 A. As you mentioned, I do recall 14 having discussions with clinicians concerning a 15 lower dose than twenty of Prozac. 16 Q. Mister Tauscher explains the 17 rationale for this that there are three patient 18 group reflected in the request, correct? 19 A. That's what the document 20 states. 21 Q. A, Side effects-Patient 22 tolerance. There are patients who can't tolerate 23 the normal dose, and other patients who do well, 24 but suffer a dosage-related side effect, correct? Page 274 1 A. That's what the document 2 states. 3 Q. Do you agree with that? 4 A. That is a true statement 5 concerning some patients, yes. 6 Q. That there's an additional B, 7 special patient population, elderly with 8 concomitant medical illnesses, often require low 9 dose on use of Prozac. In adolescents -- 10 probably should be and adolescents -- also 11 require lower doses, correct? 12 A. That's what the document 13 states. 14 Q. And that there was another 15 group of patients who on long-term therapy 16 developed symptoms of fatigue, and reducing the 17 dosage allows the patients to continue therapy, 18 correct? 19 A. That's what the document 20 states. 21 Q. So there are some patients who 22 have less side effects at lower dosage of Prozac, 23 correct? 24 A. The document is offering the Page 275 1 possibility that patients at twenty milligrams 2 that have side effects may not have those side 3 effects at a lower dose than twenty milligrams. 4 Q. Do you agree that that is 5 probable? 6 A. For some patients, that is a 7 probability, yes. 8 Q. Are you aware, Doctor Wheadon, 9 of any study using Prozac that has been 10 completed, as far as the last patient has taken 11 the last dosage of Prozac called for under the 12 protocol, that has not had a final report done on 13 such study? 14 A. I'm not aware of such. 15 Q. You understand what I'm 16 asking, that is that you've got a study 17 completed, and for some reason no final report 18 has been written, therefore no conclusions have 19 been rendered in connection with the study? 20 A. I'm not aware of such study. 21 MR. FREEMAN: Sixty seconds. 22 (DISCUSSION OFF THE RECORD.) 23 Q. Let me ask you this one final 24 question since Mister Freeman is getting Page 276 1 irritable again: Did you ever talk with any 2 clinician who felt that Prozac was the cause of 3 suicidal ideation, a suicide attempt or a 4 completed suicide on the part of their patient? 5 A. I did speak with clinicians 6 that offered the possibility that Prozac was the 7 cause of suicidal ideation or behavior in their 8 patient, yes. 9 Q. All right. Now was that 10 individual an investigator or was this in the 11 post-marketing sense, not dealing with a clinical 12 trial, or both? 13 A. This was in the post-marketing 14 sense, a physician, private practice, not 15 involved with the clinical trial. 16 Q. Did you ever talk with any 17 physicians who had had patients who had 18 experienced violent aggressive behavior who had 19 expressed the opinion that Prozac was the cause 20 of that violent aggressive behavior? 21 A. I do not recall discussing 22 with physicians that had the opinion that Prozac 23 caused violent aggressive behavior in their 24 patient, I don't recall such discussion. Page 277 1 Q. Do you recall discussions with 2 any individual whether or not they felt that 3 violent aggressive behavior and Prozac were 4 related? 5 A. I have fielded phone calls 6 from non-health care professionals that offered 7 the opinion that Prozac was the cause of violent 8 or aggressive behavior in an individual. 9 Q. Were those individuals who 10 were taking Prozac with whom you were speaking? 11 A. On at least one instance, yes. 12 Q. Tell me about that 13 conversation. 14 A. Again, it's -- I can't recall 15 specifics, it's just a patient that called the 16 company and ended up on my phone line. 17 Q. Did you -- do you recall what 18 the violent aggressive behavior was? 19 A. I do not recall specifically, 20 no. 21 Q. Do you recall whether or not 22 that patient had expressed previous episodes of 23 violent aggressive behavior prior to taking 24 Prozac? Page 278 1 A. The patient had expressed that 2 they had not had such behavior before Prozac. 3 Q. Was that patient still on 4 Prozac when you talked to them? 5 A. I do not recall. 6 Q. Do you recall that the patient 7 related that violent aggressive thoughts or 8 behavior had diminished with the discontinuation 9 of Prozac? 10 A. I don't recall the patient 11 being off Prozac at the time I spoke with the 12 patient. 13 Q. And you don't recall the 14 nature of the violent aggressive behavior? 15 A. I do not. 16 Q. Do you recall whether it was a 17 man or woman that reported that to you? 18 A. I recall that it was a male 19 individual. 20 Q. Was it just one instance? 21 A. Yes. 22 Q. How many instances have you 23 had where physicians have reported to you that 24 they felt that suicidal ideation attempts or Page 279 1 completed suicide acts were related to Prozac? 2 A. I can't recall an exact 3 number. It's more than one, but fewer than, say, 4 eighty. 5 Q. More than forty? 6 A. Again, to do a ballpark 7 figure, say forty to forty-five instances, that 8 is purely ballpark. 9 Q. Do you recall when you first 10 received reports of that nature? 11 A. These discussions all occurred 12 post the appearance of the Teicher article in 13 February of 1990. 14 Q. All right. Did you make any 15 investigation of those forty or forty-five 16 instances where it was reported to you that the 17 individual's physician felt that the suicidality 18 was related to Prozac? 19 A. It was company policy those 20 reports were filed as adverse events with 1639 21 adverse event reports. And where possible, I 22 attempted to get further information from the 23 physician. 24 Q. Do you remember whether or not Page 280 1 you ever made, of those forty or forty-five 2 instances where private physicians reporting to 3 you were reporting to you that they felt there 4 was a relationship between the suicidal -- 5 suicidality and Prozac, whether or not you 6 checked reasonably, possibly related on the 7 working form that you were required to fill out? 8 A. Well, that designation is done 9 for what's viewed by FDA mandate as a serious 10 adverse event. So if it were a report of a 11 suicide attempt that didn't involve a life 12 threatening act, didn't involve hospitalization, 13 didn't involve death or overdose, all of the sort 14 of designators of serious by FDA mandate, then 15 causal relationship would not necessarily have 16 been assigned. 17 Q. My question is did you assign 18 a causal relationship to any of those forty or 19 forty-five reports that were made to you where 20 the physician had assigned causal relationship 21 between Prozac and suicidality? 22 A. If the physician made an 23 opinion, offered an opinion about possible 24 causality, that is what was recorded on the 1639 Page 281 1 sheet in those instances. 2 Q. Where would this have been 3 recorded? 4 A. In the text of the report, and 5 if it was an adverse event that required checking 6 the causality box because it was a serious 7 adverse event, as I described, and that causality 8 box would be checked as possibly related as per 9 the treating physician. 10 Q. Did you ever make an 11 independent judgment yourself? 12 A. If the treating physician did 13 not offer an opinion, but the causality was 14 required, then an independent judgment was made 15 by myself, yes. 16 Q. Did you ever check yes, 17 reasonably related to any reports of suicidality 18 in connection with Prozac? 19 A. I have checked possibly 20 related in conjunction with some reports of 21 suicidality in patients on Prozac, yes. 22 Q. Can you give me an approximate 23 number? 24 A. I cannot give you an Page 282 1 approximate number. 2 Q. Would it be more than one? 3 A. It would be more than one. 4 Q. Would it be more than forty? 5 A. I really can't say that it's 6 more than forty or less than sixty, I really 7 cannot recall a specific number. 8 Q. Would forty to sixty be 9 something that you could live with comfortably? 10 A. Forty would be a reasonable 11 number to propose, but I don't recall exactly. 12 Q. And I'm not trying to hold you 13 to specific numbers. 14 Q. All right. 15 MR. DOWNEY: Can I clarify real quick, 16 Paul, those forty times were those times -- or 17 does that just include times where you made the 18 decision as to causality or does that also 19 include the times when the reporting physician 20 indicated causality? 21 THE WITNESS: The question was in 22 response to my independent assessment where a 23 physician was not offering an opinion. 24 MR. DOWNEY: I wasn't sure, thanks. Page 283 1 MR. SMITH: Don't ever answer a 2 question from a guy from California. 3 MR. HARRIS: That was more than one 4 final question. 5 MR. SMITH: No further question. 6 * * * * * * * * * * 7 (THE DEPOSITION WAS ADJOURNED 8 UNTIL THE FOLLOWING DAY, JUNE 9 10, 1994, WHEREUPON IT CONTINUED 10 AS FOLLOWS:) 11 12 * * * * * * * * * * 13 14 CONTINUING DIRECT EXAMINATION 15 BY MR. SMITH: 16 Q. Good morning, Doctor Wheadon. 17 A. Good morning. 18 Q. Thank you for coming back. 19 Doctor Wheadon, as I understand it, when you 20 joined Lilly in 1987, you started working on 21 Prozac relatively soon, is that correct? 22 A. That is correct. 23 Q. And your first work was sort 24 of some clean up with respect to the submission Page 284 1 to the Food and Drug Administration? 2 A. I was to assist with the final 3 negotiations between the company and the FDA in 4 terms of the final approval of Prozac for 5 depression, things such as the summary basis for 6 approval, safety updates, what have you. 7 Q. Did any of that work have to 8 do with package insert language? 9 A. No, it did not. 10 Q. Do you recall who it was that 11 was working at Lilly on the package insert 12 material? 13 A. My recollection is that Joe 14 Wernicke, in conjunction with the regulatory 15 affairs office, were directly responsible for the 16 package insert language. 17 Q. Do you recall approximately 18 how many clinical trials had been completed up to 19 the time that you joined Lilly? 20 A. I don't recall that number, 21 no. 22 Q. Would it have been ten, fifty, 23 a hundred, can you give us any estimate? 24 A. I don't recall that number. Page 285 1 Q. During the time that you were 2 at Lilly, how many clinical trials did you 3 participate in in any capacity? 4 A. On Prozac? 5 Q. Yes, sir. I'm not interested 6 in work you did on any other compounds. 7 A. On the order of ten. 8 Q. You mentioned yesterday an OCD 9 trial, and I think I've seen that you worked on a 10 schizophrenia trial? 11 A. The schizophrenia trial was 12 not on Prozac. 13 Q. There were discussions 14 concerning a possible Prozac schizophrenia trial, 15 were there not? 16 A. I don't recall the discussions 17 concerning a Lilly sponsored Prozac schizophrenia 18 trial. 19 Q. My recollection is that I saw 20 some documents from your file where you had had a 21 discussion with Doctor Paul Leber at the FDA 22 regarding the possibilities of a Prozac 23 schizophrenia trial. 24 A. I do not recall discussions Page 286 1 with Paul Leber concerning a Prozac schizophrenia 2 trial. 3 Q. Maybe Tom Laughren? 4 A. I don't recall a conversation 5 with Tom Laughren on a Prozac schizophrenia 6 trial. 7 (DISCUSSION OFF THE RECORD.) 8 (PLAINTIFFS' EXHIBIT NO. 14 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. All right. Have you had an 12 opporunity to review Exhibit No. 14? 13 A. Yes, I have. 14 Q. And that is a memo dated 15 February 21, 1990 authored by you, is it not? 16 A. That's correct. 17 Q. And it concerns a telephone 18 conversation that you had with Doctor Tom 19 Laughren at the FDA? 20 A. That is correct. 21 Q. And it concerns a clinical 22 trial with respect to schizophrenia, does it not? 23 A. Concerns placebo controlled 24 clinical trials on schizophrenia, that is Page 287 1 correct. 2 Q. Was that a trial involving 3 Prozac? 4 A. It was not. 5 Q. Was that a trial involving 6 another drug? 7 A. It involved another Lilly drug 8 that is not approved. 9 Q. The reason I ask is that under 10 court order, we were not to receive any material 11 concerning nonapproved or other drugs other than 12 Prozac. That's why I had the assumption that 13 this would deal with Prozac since it had been 14 produced. 15 A. I cannot explain why this was 16 provided to you, but it did not involve Prozac. 17 Q. All right. Is the other 18 medication that's the subject of this discussion 19 an antidepressant? 20 A. No, it's not. 21 Q. How about schizo-affective 22 disorder, was Prozac ever used in any study or 23 planned for use in any study of schizo-affective 24 disorder? Page 288 1 A. Prozac, to my knowledge, was 2 not used or planned to be used in any Lilly 3 sponsored study on schizo-affective disorder. 4 Q. Do you know if there were 5 grants or other studies using Prozac with respect 6 to schizo-affective disorder? 7 A. I do not recall any grants to 8 investigators to use Prozac in schizo-affective 9 disorder. 10 Q. Do you know of any study done 11 by anybody at any time using Prozac and studying 12 schizo-affective disorder? 13 A. I do not recall at this time 14 any studies involving Prozac and schizo-affective 15 disorder. 16 Q. Now the other -- you mentioned 17 that you were involved in ten trials, one OCD 18 trial. 19 A. Two. 20 Q. Two OCD trials. Would that 21 mean that the other eight trials involved 22 depression? 23 A. Not exclusively, no. 24 Q. What other indications for Page 289 1 uses were the subject of these other trials? 2 A. Bulimia nervosa, smoking 3 cessation, depression in the elderly, I think 4 that encompasses the bulk of it. 5 Q. So the rest of them would have 6 been depression trials? 7 A. The one depression trial that 8 I remember is the one I noted, depression in the 9 elderly. 10 Q. Geriatric depression? 11 A. That's correct. 12 Q. And that's the only depression 13 trial you were involved in? 14 A. That I recall. 15 (PLAINTIFFS' EXHIBIT NO. 15 WAS 16 MARKED FOR IDENTIFICATION AND 17 RECEIVED IN EVIDENCE.) 18 Q. Review Exhibit 15 with me, 19 would you, Doctor? 20 (WITNESS REVIEWS DOCUMENT.) 21 Q. Exhibit 15 is a note to you 22 from Mister Gary Tauscher, correct? 23 A. That is correct. 24 Q. It indicates that there's Page 290 1 going to be introduction of Prozac to the medical 2 community, correct? 3 A. It states as we begin the 4 introduction to the medical community, yes. 5 Q. And this was shortly after you 6 joined -- well, six or eight months after you 7 joined Lilly? 8 A. That's correct. 9 Q. Do I take it from this that 10 you assisted marketing as a clinical research 11 physician or, I guess, then, as an assistant 12 clinical research physician, in giving 13 presentations to various physician groups? 14 A. This particular document 15 refers to my giving presentations to in-house 16 groups, such as sales representatives, sales 17 training organizations, that sort of thing. 18 Q. After that, did you later make 19 presentations to physician groups? 20 A. That is correct. 21 Q. Did you make presentations to 22 psychiatrists? 23 A. Yes. 24 Q. And then did you make Page 291 1 presentations to general practitioners? 2 A. Yes. 3 Q. Or physicians in other 4 specialties other than psychiatry? 5 A. My presentations were limited 6 solely to psychiatrists or to groups of general 7 practitioners or family practitioners. 8 Q. With respect to the 9 psychiatrists that you spoke to, on how many 10 occasions did you speak to psychiatric groups? 11 A. I do not recall. 12 Q. Would it have been on more 13 than one occasion that you spoke to groups of 14 psychiatrists? 15 A. That is correct. 16 Q. Did you deal with the Lilly 17 psychiatric advisory board in any way? 18 A. Yes, I did. 19 Q. In what capacity did you deal 20 with that group? 21 A. As a representative of the 22 medical department of Lilly. 23 Q. On how many occasions did you 24 meet with the Lilly psychiatric advisory Page 292 1 committee? 2 A. I do not recall. 3 Q. With respect to the 4 presentations that you made to psychiatrists in 5 private practice, and I assume these 6 psychiatrists were in private practice? 7 A. Not exclusively, no. 8 Q. Some were, though? 9 A. Some were, yes. 10 Q. What would the others have 11 been involved in? 12 A. Academic affiliations. 13 Q. Do you recall in those 14 discussions yourself or anyone of the Lilly group 15 mentioning to those psychiatrists the 16 relationship of Prozac and suicide? 17 A. I did give presentations to 18 groups of psychiatrists concerning the analyses 19 of the data, Lilly clinical trial data base, on 20 the issue of Prozac and suicide. 21 Q. And you were the individual 22 that made those presentations dealing with 23 suicide? 24 A. To a large extent, yes. Page 293 1 Q. Were there any other 2 physicians that you recall that made these 3 presentations to the psychiatrists? 4 A. I recall correctly other 5 physicians in the Lilly medical group on occasion 6 did make presentations concerning the data on 7 Prozac and suicide. 8 Q. And do you recall what you 9 advised the psychiatrists concerning what the 10 data was with respect to Prozac and suicide? 11 A. My recollection is that based 12 on the data I presented to these groups of 13 physicians, psychiatrists, and primary care 14 practitioners, that there was no evidence to 15 indicate a causal association between Prozac and 16 suicidal thinking or behavior. 17 Q. Do you recall whether or not 18 there were any questions raised by any of the 19 psychiatrists concerning the relationship between 20 Prozac and suicidal behavior? 21 MR. FREEMAN: Read the question again, 22 please. 23 (THE COURT REPORTER READ BACK THE 24 REQUESTED TESTIMONY.) Page 294 1 A. Yes, there were several 2 questions raised by psychiatrists concerning the 3 relationship between Prozac and suicidal 4 behavior. 5 Q. Do you recall what those 6 questions were? 7 A. Some of them, yes. 8 Q. Tell me those questions that 9 you recall. 10 A. The questions consisted of 11 things such as I have not seen this, I don't 12 understand why this is an issue, can you explain 13 that to me. Questions such as what was the role 14 or what is the role of the Church of Scientology 15 in this trumped up issue, questions such as the 16 data seems very promising, what other things will 17 be coming, will this data be published so I can 18 use it in educating my patients, questions such 19 as what exactly is it that Doctor Teicher is 20 describing in his case reports, I don't 21 understand it, questions such as weren't suicidal 22 patients prevented from going into these clinical 23 trials, then how can you assess this data base 24 for suicidality. Those are the sorts of Page 295 1 questions I would be asked at these 2 presentations. 3 Q. Do you recall generally what 4 your response to those questions would be? 5 A. You would have to repeat the 6 individual questions, and I can then tell you 7 what my general responses were. 8 Q. Well, were your responses 9 generally that there was no evidence in the 10 clinical trial data to support any conclusion 11 that there was a causal connection between Prozac 12 and suicide? 13 A. As I have stated that my 14 conclusions from my talk were that there was no 15 scientific evidence based on the data that I 16 presented to indicate a causal relationship 17 between Prozac and suicidal thinking or behavior. 18 Q. Were there ever any of the 19 physicians who reported to you in these meetings 20 that they had had patients that had experienced 21 suicidal ideation or attempts while on Prozac, 22 and they were questioning whether or not you had 23 an opinion concerning whether or not their 24 patient's suicidality would have been caused by Page 296 1 the ingestion of Prozac? 2 A. You asked a two-part question, 3 and I'll answer it in two parts. 4 Q. That would be fine. 5 A. Physicians did raise the -- or 6 make the point that they had seen patients that 7 had suicidal ideation or behavior while on Prozac 8 treatment, however I was not asked on any one 9 individual patient whether or not I thought 10 Prozac causes suicidal ideation in the patient 11 that the physician was discussing with me. 12 Q. When those patients would -- 13 when these physicians reported that they had had 14 patients that had had suicidal behavior on 15 Prozac, did you ask for any information from them 16 concerning details of the particular cases? 17 A. As is our standard procedure, 18 once we hear of an adverse event report on any 19 Lilly product, we do attempt to get more 20 information from the reporter. 21 Q. So would the answer to my 22 question be yes, I did ask them details? 23 A. If there was more information 24 to be obtained, I did attempt to get more Page 297 1 information from the reporter. 2 Q. Do you recall receiving any 3 information at one of these meetings that led to 4 a more in-depth discussion of the question in 5 general or specifically with respect to whether 6 or not a particular patient might have had a 7 causal connection between his or her Prozac usage 8 and the suicidality? 9 A. I do not recall a conversation 10 where there was further discussion of the 11 possible relationship between Prozac and the 12 patient's suicidal behavior, the discussions were 13 around getting more medical history concerning 14 the patient. 15 Q. Would there have been any 16 difference in the information that you had given 17 the psychiatrists in these meetings than the 18 information that you gave to the general 19 practitioners in these meetings? 20 A. No, there was no difference. 21 Q. With respect to these 22 meetings, I'm going to ask you the same series of 23 questions with respect to aggressive violent 24 homicidal behavior, all right, sir. Did any of Page 298 1 the physicians in any of these meetings question 2 you concerning whether or not there was an 3 association in Prozac or an association of Prozac 4 and violent aggressive behavior? 5 A. There were questions raised 6 concerning the association between Prozac and 7 violent or aggressive behavior. 8 Q. What was your response to 9 those questions? 10 A. I had a series of slides 11 concerning data analyses and Lilly clinical 12 trials around that question which I would share 13 with the group and add the conclusion that based 14 on the evidence presented, there was no 15 indication of a causal relationship between 16 Prozac and violent or aggressive behavior. 17 Q. Would your presentation have 18 been the same to psychiatrists as well as general 19 practitioners? 20 A. Yes, it would have been. 21 Q. In any of those meetings, did 22 any psychiatrists or general practitioners report 23 to you that they had had patients that had 24 experienced violent aggressive or homicidal Page 299 1 behavior on Prozac? 2 A. I do not recall reports of 3 homicidal behavior in these meetings, I do recall 4 clinicians offering case reports of patients 5 having aggressive behavior during treatment of 6 Prozac. 7 Q. Was there any particular 8 general nature of the aggressive behavior? 9 A. No, not particularly. 10 Q. But when you say aggression, 11 are you talking about some type of physical 12 response? 13 A. In general, when I say 14 aggression I mean acts outwardly intended, either 15 breaking dishes, breaking down a door, things 16 such as that. 17 Q. As opposed to anxiety or 18 agitation? 19 A. That's correct. 20 Q. Aggressive behavior in your 21 mind, maybe in psychiatry generally, indicates 22 some type of act, is that right? 23 A. Some outwardly directed act, 24 yes. Page 300 1 Q. And did you say you did recall 2 or did not recall whether or not any of the 3 psychiatrists or general practitioners that you 4 spoke with in these meetings had reported 5 aggressive acts on the part of their patients 6 while taking Prozac? 7 A. As I mentioned, I did recall 8 physicians citing cases of patients with 9 aggressive behavior while on Prozac treatment. 10 Q. And did they ask your opinion, 11 sir, concerning whether or not you felt that that 12 aggression was related to Prozac? 13 A. No, they did not, not on those 14 individual cases. 15 Q. Did you express any opinion? 16 A. Not on those individual cases, 17 no. 18 Q. But generally, your statements 19 to those groups of physicians was that the data 20 did not support the conclusion that Prozac was 21 causally related to aggressive behavior? 22 A. That's correct. 23 (DISCUSSION OFF THE RECORD.) 24 (PLAINTIFFS' EXHIBIT NO. 16 WAS Page 301 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.). 3 Q. Doctor Wheadon, Exhibit 16 is 4 a document that Lilly has produced concerning a 5 presentation to the board of directors of Eli 6 Lilly and Company that occurred on October 20, 7 1986. Is that what it appears to you, sir? 8 A. The document is dated October 9 20, 1986, and it indicates an update for a board 10 meeting, yes. 11 Q. The cover letter is dictated 12 by Doctor Leigh Thompson, correct? 13 A. That's correct. 14 Q. Turn with me to page two of 15 the document, down under the safety section. Do 16 you see that? 17 A. Yes, I do. 18 Q. It says worldwide exposure of 19 Fluoxetine now totals fifty-six hundred and fifty 20 subjects and patients to a total of one thousand 21 patient years. The longest exposure is about six 22 point five years. No new issues have appeared 23 since the NDA was submitted. The major medical 24 concerns are suicide in depressed patients and Page 302 1 rats. Minor or adverse events include nausea in 2 about one-fourth of the patients that causes 3 discontinuation from studying about three percent 4 of depressed patients, and rarely is associated 5 with vomiting, correct? 6 A. That is the way it reads. 7 Q. Had you ever seen this before 8 in your review of documents or review of file 9 materials at Lilly? 10 A. No, I have not. 11 Q. Did you know that in October 12 of 1986, the major medical concerns were suicide 13 in depressed patients and rats? 14 A. No, I did not. 15 Q. Reading with me, Doctor, on 16 that page, it says the drug tends to be alerting 17 or more -- with more insomnia, sleep disorders 18 and anxiety than other depressants. Do you see 19 that? 20 A. That is what it reads, yes. 21 Q. Is this consistent with your 22 opinion concerning Prozac, that it is alerting 23 with more insomnia, sleep disorders, and anxiety 24 than other antidepressants? Page 303 1 A. That is not in keeping with my 2 opinion of Prozac, no. 3 Q. Did you advise any of the 4 physicians at either the psychiatrist meetings or 5 meetings with the general practitioners that 6 Prozac tends to be alerting with more insomnia, 7 sleep disorders, and anxiety than other the 8 antidepressants? 9 A. No, I did not use those words, 10 no. 11 Q. Did you know that the board of 12 directors of Eli Lilly and Company had been 13 advised in October of 1986 that the drug tends to 14 be alerting with more insomnia, sleep disorders, 15 and anxiety than other antidepressants? 16 A. No, I did not. 17 (PLAINTIFFS' EXHIBIT NO. 17 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Doctor, you're certainly free 21 to review all of this document. My questions are 22 going to be focused around point eight on page 23 two. 24 A. Thank you. Page 304 1 Q. Exhibit 17 appears to be a 2 review of Fluoxetine safety update authored by 3 Marlene L. Cohen, Ph.D, correct? 4 A. That's correct. 5 Q. Do you know Doctor Cohen? 6 A. Yes, I do. 7 Q. Who is Doctor Cohen? 8 A. She's one of the basic 9 scientists at Lilly. 10 Q. Do you know what her 11 discipline is? 12 A. I don't recall exactly, no. 13 Q. Did you have the opportunity 14 to work with Doctor Cohen at any time during your 15 tenure with Lilly? 16 A. I worked with Doctor Cohen in 17 the form of participating on project teams along 18 with her. 19 Q. Did you find her to be a 20 competent individual? 21 A. I found Doctor Cohen to be a 22 competent basic scientist, yes. 23 Q. What is a safety -- this 24 document indicates it's a review of Fluoxetine Page 305 1 safety update, what is the safety update? 2 A. Not having seen the document 3 before nor knowing exactly what Doctor Cohen is 4 referring to, it's difficult for me to answer 5 that question. 6 Q. But isn't there supposed to be 7 submitted a safety update each year by Lilly to 8 the Food and Drug Administration? 9 A. There are requirements, 10 depending on where the drug is in development, to 11 have safety updates filed either to the IND or 12 the NDA, depending on where the drug is in 13 development, yes. 14 Q. But a safety update is a 15 specific document, is it not, that's required to 16 be filed with the appropriate regulatory bodies? 17 A. There are safety updates 18 required by the FDA, as I discussed, however 19 there are safety updates that are done internally 20 that are not required to be filed with the FDA. 21 Q. Such as? 22 A. Lilly does a quarterly review 23 of safety on drugs in development and on marketed 24 products. Those quarterly reviews are not Page 306 1 required to go in to the FDA. 2 Q. Aren't they called quarterly 3 reviews? 4 A. Some may use the term 5 quarterly reviews, some may use the term safety 6 update. 7 Q. Can you tell from looking at 8 this document, Doctor Wheadon, whether or not 9 this is a safety update that is done on an annual 10 basis or done on a quarterly basis? 11 A. Looking at the document in and 12 of itself, I cannot render a judgment one way or 13 the other. 14 Q. Do you know if Doctor Cohen 15 regularly worked on safety updates or whether she 16 was asked to do this on sporadic occasions? 17 A. I cannot answer how often, if 18 at all, Doctor Cohen was consulted on safety 19 updates. 20 Q. Have you ever seen this 21 document marked Exhibit 17? 22 A. No, I have not. 23 Q. Do you have any idea from 24 looking at this document, since it's not dated, Page 307 1 approximately when this document would have been 2 produced? 3 A. No, I do not. 4 Q. Turn with me to page two, 5 point eight. Doctor Cohen there says, quote, CNS 6 stimulation. And when we talk about CNS, we're 7 talking about central nervous system, are we not? 8 A. That's correct. 9 Q. Continuing to quote, CNS 10 stimulation, agitation and insomnia. From the 11 data taken in concert, it might appear that there 12 is a somewhat greater incidence of CNS 13 stimulation with Fluoxetine as compared with 14 placebo. For example, a greater incidence of 15 insomnia and anxiety was reported -- and then 16 I'll leave out the references. Continuing the 17 quote, agitation seems pronounced, and a decrease 18 in REM sleep was reported, and there may be a 19 suggestion of manic psychosis. As with other 20 antidepressants used in the depressed population, 21 mania or CNS stimulation may be a minor complaint 22 of the actions of Fluoxetine, end quote. Did I 23 read that correctly, leaving out the citations? 24 A. Yes. Page 308 1 Q. Had you ever seen this 2 analysis of the safety data? 3 A. I cannot say that I've ever 4 seen the analysis that Doctor Cohen is referring 5 to in point eight. 6 Q. Are you in a position to agree 7 or disagree with this assessment by Doctor Cohen? 8 A. Not having the analysis in 9 front of me that she's referring to, I'm not in a 10 position to agree or disagree. 11 Q. Did you advise any of these 12 physicians in these meetings that Prozac could 13 produce CNS stimulation? 14 A. When you say these meetings, 15 what are you referring to? 16 Q. These meetings we were 17 discussing earlier, where you would meet with 18 psychiatrists, and other meetings where you would 19 meet with general practitioners explaining the 20 actions of Prozac and answering their questions. 21 A. The meetings we were referring 22 to earlier were meetings concerning the possible 23 association between -- or my presentation was 24 concerning the possible association between Page 309 1 Prozac and suicidal behavior. 2 Q. Okay. 3 A. So if you're referring to 4 those meetings, I did not specifically discuss 5 the points that Doctor Cohen discusses in point 6 eight on page two of this document. 7 Q. Did you discuss it generally? 8 A. There may have been questions 9 concerning associated agitation, anxiety with 10 Prozac use. 11 Q. And what do you recall as 12 being your conclusion that you expressed to those 13 physicians concerning association of anxiety and 14 agitation with Prozac use? 15 A. That there have been reports 16 of anxiety, agitation, other adverse events of 17 that sort in patients on Prozac treatment. 18 Q. And what was your advice to 19 them concerning whether or not there was a causal 20 relationship between Prozac and that agitation 21 and anxiety? 22 A. No advice was given concerning 23 a causal relationship. The statement was that 24 there had been reports of agitation, anxiety, Page 310 1 nervousness, on patients on Prozac. 2 Q. Did you present to them 3 results of the clinical trial data in that 4 connection? 5 A. No, I did not. 6 Q. It was just conclusory 7 statements concerning that there was or had been 8 reports of agitation and anxiety that had 9 occurred during the clinical trials? 10 A. That's correct. 11 Q. But you didn't give them 12 percentages or incidents or frequencies that you 13 recall? 14 A. No, I did not, that was not 15 the purpose of my presentation at those meetings. 16 Q. Do you have an opinion, 17 Doctor, concerning whether or not CNS stimulation 18 is a minor component of the action of Fluoxetine? 19 A. When you say CNS stimulation, 20 your reference is to that term? 21 Q. Yes. 22 A. I would agree with the 23 statement that CNS stimulation is a minor 24 component of the action of Fluoxetine, that is Page 311 1 correct. 2 Q. And when you discuss CNS 3 stimulation as being a minor component of the 4 action of Fluoxetine, what do you mean, sir? 5 A. When I use the term CNS 6 stimulation, I refer to such things as anxiety, 7 nervousness, insomnia, agitation. 8 Q. Would you include aggression 9 in that group? 10 A. I would not include aggression 11 under the term CNS stimulation. 12 Q. Why? 13 A. CNS stimulation refers to 14 activation of certain processes within the CNS 15 nervous system, in my mind, leading to things 16 such as anxiety, nervousness and insomnia. 17 Aggression refers to a type of act. So I don't 18 include aggression under the term CNS 19 stimulation. 20 Q. All right. It says that mania -- 21 Doctor Cohen says mania may be a minor component 22 of the actions of Fluoxetine, does she not? 23 A. The statement is there may be 24 a suggestion of manic psychosis is what she says. Page 312 1 Q. Right. Then in the last 2 sentence, I believe, she does use the term mania, 3 does she not? 4 A. As with other antidepressant 5 agents used in the depressed population, mania 6 may be a minor component to the actions of 7 Fluoxetine, yes. 8 Q. What is manic psychosis? 9 A. Manic psychosis refers to 10 psychotic sort of processes in a patient that is 11 experiencing a manic episode. So that could be 12 delusions, delusions being fixed false beliefs 13 that these patients have special powers, for 14 example. They may at times have auditory 15 hallucinations, they hear voices that aren't 16 there. That's generally what manic psychosis 17 refers to. So psychotic symptoms in the context 18 of a manic episode. 19 Q. Let's see if we can break down 20 that. What is a manic episode? 21 A. Manic episode is typically 22 seen, but not exclusively, in a patient with what 23 we call bi-polar disorder, a patient that has 24 both depression as well as periods of extreme Page 313 1 euphoria, racing thoughts, increased energy. In 2 some cases, psychotic overtones as we were 3 discussing, delusions, hallucinations, that sort 4 of thing. 5 Q. And these delusions or 6 hallucinations might be manifested, you said, as 7 a fixed belief, as true, of something that is in 8 fact false? 9 A. The definition of a delusion 10 is a fixed false belief. The patient believes it 11 to be true, but in reality it is not true. 12 Q. Such as I'm Dwight D. 13 Eisenhower? 14 A. Exactly. 15 Q. Or somebody is after me? 16 A. Yes. 17 Q. Or somebody is out to get me? 18 A. It can take that form, yes. 19 Q. Or my co-workers don't like 20 me? 21 A. It could possibly take that 22 form, but again, it's a matter of deciding that 23 that is indeed false. When you talk about 24 co-workers not liking someone, it may not be Page 314 1 false. 2 Q. May be true or not? 3 A. Exactly. 4 Q. But let's assume there wasn't 5 any evidence that the co-workers didn't like a 6 particular individual, and that individual says 7 nobody likes me here, that would be an example of 8 what you're speaking about when you're talking 9 about manic psychosis, is that right, or 10 psychosis? 11 A. That could conceivably be an 12 example of psychosis, either by itself or in the 13 context of mania, yes. 14 Q. And it's your opinion that 15 this can be seen in connection with Prozac? 16 A. Mania or associated manic 17 psychosis may be seen in patients with bi-polar 18 disorder under treatment with any antidepressant, 19 including Prozac. 20 Q. And that's what you assume 21 Doctor Cohen is referring to? 22 A. Again, not having the benefit 23 of whatever data she was reviewing, I can't 24 render an opinion on that. Page 315 1 Q. All right. Doctor Cohen 2 mentions a decrease in REM sleep. Do you see 3 that? 4 A. Yes. 5 Q. In association with Prozac, 6 correct? 7 A. Yes. 8 Q. What is REM sleep? 9 A. REM refers to rapid eye 10 movement sleep, it's a stage of sleep. There's 11 several stages that we go through when we fall 12 asleep and while we're sleeping, REM is in the 13 early stages of sleep, it's really the deepest 14 sleep that we go into. 15 Q. Is that an important stage of 16 sleep? 17 A. It's viewed as the most 18 restful stage of sleep. 19 Q. And is it necessary, normally, 20 for an individual to have some REM sleep? 21 A. Well, I would say that it's 22 normal for an individual to have some REM sleep. 23 Q. What's the difference in REM 24 sleep and other types of sleep? Page 316 1 A. On a general -- or in general, 2 the difference is really where REM sleep occurs 3 in the overall stage. REM sleep is earlier in 4 the overall sleep process, it's also a deeper 5 sleep compared to the later stages of sleep. 6 Q. What are the later stages of 7 sleep known as? 8 A. You now have probably gone 9 beyond the extent of my expertise, I am not a 10 sleep expert. 11 Q. But you're sufficiently 12 familiar with REM sleep to know that it is an 13 important portion of our sleep process? 14 A. Yes. 15 Q. And are you aware that Prozac 16 affects the quality of REM sleep? 17 A. I'm aware that in Prozac, as 18 other antidepressants, it is a common 19 characteristic for antidepressants to have a 20 decrease -- an effect on REM sleep, that being a 21 decrease in REM. 22 Q. Could this account, the fact 23 that Prozac can affect the amount of REM sleep, 24 be related to some of the reasons that you find Page 317 1 agitation, anxiety, and nervousness associated 2 with Prozac? 3 A. I don't believe, nor am I 4 aware of an opinion, that the effect on REM has 5 any association with the occurrence of agitation 6 or anxiety in patients on any antidepressant or 7 on Prozac. 8 Q. I've seen it postulated that 9 individuals who do not get the proper sleep are 10 more agitated and anxious, cranky, short 11 tempered, than individuals who have gotten a 12 sufficient amount of sleep. Is that correct or 13 incorrect? 14 A. The notion of someone being 15 cranky or agitated after not getting sufficient 16 sleep is generally true, yes. 17 Q. Sleep deprivation can produce 18 anxiety and agitation and nervousness? 19 A. I don't necessarily agree with 20 that statement. 21 Q. What part do you not agree 22 with? 23 A. Sleep deprivation in and of 24 itself does not lead to anxiety, agitation or Page 318 1 nervousness, no. 2 Q. Is it related to those terms? 3 A. You may see in a patient that 4 is sleep deprived crankiness, anxiety, 5 nervousness. 6 Q. Can sleep deprivation produce 7 or exacerbate psychosis? 8 A. I'm not aware of data 9 indicating that sleep deprivation produces nor 10 exacerbates psychosis. 11 Q. Is there any correlation to 12 REM sleep in individuals suffering from 13 psychosis? 14 A. I'm not aware of any data 15 correlating a lack or an increase of REM sleep 16 and psychosis. 17 Q. All right. Doctor Wheadon, 18 there has been testimony in this case that after 19 February, 1990, there was an effort made by Lilly 20 to analyze the data collected in the clinical 21 trials outside the United States, specifically 22 some employees of Lilly went over to Europe and 23 collected case report forms looking for 24 possibilities of suicidal or violent aggressive Page 319 1 behavior, and then those case report forms and 2 material of that nature was transmitted to the 3 clinical research physicians at Lilly for further 4 review. Do you have knowledge concerning those 5 events? 6 A. Yes. 7 Q. All right. Were you one of 8 the clinical research physicians who was 9 reviewing that information? 10 A. That is correct. 11 Q. All right. When was it, do 12 you recall, that employees of Lilly went over to 13 Europe to collect this data? 14 A. If I recall correctly, it was 15 during the summer of 19 -- I think late summer of 16 1990, or it may have been 1991 -- I think it was 17 1991. 18 Q. And did you physically go to 19 Europe? 20 A. Not as part of that effort, 21 no. 22 Q. Who do you recall went to 23 Europe? 24 A. I recall Laura Fludzinski, who Page 320 1 was a CRA, being involved in that trip. I think 2 I also recall Catherine Mesner, another CRA, 3 being involved in that trip. Those are the two 4 people I can recall specifically. 5 Q. In September of 1991, were you 6 the global clinical monitor or the global 7 physician? 8 A. I don't recall exactly when I 9 was designated that, so I can't recall exactly. 10 Q. On several occasions, you've 11 sort of poo-pooed that title, was that a title in 12 name only and really didn't have any 13 responsibilities associated with it? 14 A. I wouldn't say it was a title 15 in name only, it was a title assigned during the 16 process of restructuring the architecture of the 17 medical group. So while the title was given, the 18 actual role of the global physician had not been 19 clearly established at the time I left Lilly. 20 Q. And did it really impact what 21 you were doing on a day-to-day basis, this 22 change? 23 A. Not in a significant degree, 24 no. Page 321 1 (DISCUSSION OFF THE RECORD.) 2 (PLAINTIFFS' EXHIBIT NO. 18 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.). 5 Q. Exhibit 18 is a document dated 6 June 14, 1991, signed by Suzanne Myers, is it 7 not? 8 A. That's correct. 9 Q. And who was Ms. Myers? 10 A. Ms. Myers was the secretary to 11 Doctor Dan Masica. 12 Q. It's signed by her, but above 13 that it's designated "the working group," isn't 14 it? 15 A. That is the designation, yes. 16 Q. Are you familiar with that 17 term, the working group? 18 A. If I recall correctly, the 19 working group referred to the group of 20 individuals who were in Europe collecting the 21 case report forms and sending them back for 22 review, what have you. 23 Q. This is dated June, 1991, and 24 says the international suicide report will be Page 322 1 sent to the FDA on Monday, June 17, correct? 2 A. That's correct. 3 Q. And that the final draft will 4 be in David Wheadon's office on Monday, June 5 17th, from 9:00 a.m. to 1:00 p.m., correct? 6 A. That's correct. 7 Q. So does this help you -- could 8 it have been 1990 that the group went over to 9 Europe, in the summer of '90? 10 A. Again, I don't recall the 11 exact dates of the trip of that group. 12 Q. Does this help you in making 13 that recollection? 14 A. It very well may indicate that 15 the trip that the group took was indeed not in 16 the summer, but sometime in the fall of '90 or 17 early 1991, I just cannot remember the date. 18 Q. It says we appreciate your 19 comments and suggestions from the first review. 20 Do you see that? 21 A. That is a sentence in the 22 statement, yes. 23 Q. Would that indicate that there 24 might have been two occasions where CRAs and Page 323 1 individuals such as that went to Europe to 2 collect this data or was there just a preliminary 3 review of the data? 4 A. I think it indicates there was 5 a first review of the report, changes 6 incorporated based on that review. And then as 7 the document indicates, there needed to be a 8 final review of the report. 9 Q. As far as you know, there was 10 only one instance where employees went to Europe 11 to collect this data? 12 A. As far as I recall, there was 13 one trip where the employees went to Europe, 14 stayed for a period of time, collected the case 15 report forms, including having them translated, 16 and then returned the information to 17 Indianapolis. 18 Q. Do you recall how much 19 material, as far as volume or number of 20 documents, was brought back or sent back? 21 A. I do not recall. 22 Q. Was it a large volume of 23 documents? 24 A. Yes. Page 324 1 Q. And were these documents that 2 you and the other physicians were to review? 3 A. That's correct. 4 Q. And the other physicians 5 reviewing those documents were Doctors Beasley 6 and Heiligenstein as well as yourself? 7 A. Yes, that's correct. 8 Q. Was there any other physicians 9 that reviewed those documents? 10 A. In terms of reviewing of 11 documents, as had been done in the U.S. data 12 analysis, we were the three responsible, that's 13 correct. 14 Q. And would it be accurate to 15 state that a particular act or instance of 16 potentially suicidal behavior would be addressed 17 as a hit? 18 A. That was the term that was 19 used, yes. 20 Q. Now, was this suicidality 21 documents or acts only or did these acts include 22 instances of violent aggressive or homicidal 23 behavior? 24 A. The review of the Page 325 1 international data base, meaning the European 2 case report forms, were specifically around 3 suicidal behavior. 4 Q. Was there any review of the 5 European data with respect to violent aggressive 6 homicidal behavior? 7 A. I do not recall a review 8 around -- of the European data around violence or 9 aggression. 10 Q. And by violence and 11 aggression, would you include homicidal behavior? 12 A. Yes. 13 Q. Why was there no analysis made 14 of violent aggressive or homicidal behavior of 15 the OUS data? 16 A. I do not recall that number 17 one, the analysis was done, or number two, if 18 that is indeed the case, why it was not done. 19 Q. You didn't do any analysis of 20 OUS data concerning violent aggressive behavior? 21 A. That is correct. 22 Q. And you're not aware of any 23 that was done. 24 A. That is correct. Page 326 1 Q. And you don't know of any 2 reason why it was not done? 3 A. That is correct. 4 Q. Do you recall any discussions 5 whatsoever concerning clinical trial data outside 6 the U.S. with regard to aggressive violent 7 behavior? 8 A. I do not recall any discussion 9 of such. 10 Q. And don't recall any 11 suggestion then that something of that nature 12 should be done? 13 A. I don't recall, no. 14 Q. Now when the case report forms 15 on suicidality got back to you as well as the 16 other physicians here -- there in Indianapolis, 17 what physically did you do? 18 A. Again, it was a case-by-case 19 review of the case report forms looking for 20 indications of suicidal behavior or thinking. 21 Q. All right. What guidelines 22 did you use to define indications of suicidal 23 behavior or thinking? 24 A. Any expression within the Page 327 1 context of the case report form indicating such 2 thought process or behavior. 3 Q. All right. Were you given a 4 written checklist or anything of that nature to 5 use in that connection? 6 A. There was not a written 7 checklist. There was agreement amongst the three 8 psychiatrists that in looking through the case 9 report form, any indication of a thought process 10 concerning suicide or behavior around suicidal 11 intents would constitute a positive case. 12 Q. Were there any kind of gray 13 areas or anything of that nature? 14 A. As with any case, there could 15 be a gray area where, for example, a patient may 16 have been what we call acting out, using a 17 plastic butter knife and scratching at one's 18 wrist. That was not a suicidal act with lethal 19 intent, that was not viewed as a suicidal act 20 with lethal intent. 21 Q. So are the elements that you 22 wanted -- you wanted an act with lethal intent? 23 A. That is correct. 24 Q. Act plus lethal intent. Page 328 1 Anything else used as a guideline? 2 A. As I mentioned, any mention in 3 the case report form indicating suicidal thoughts 4 or acts or completed -- or behavior, including 5 acts or completed suicide. 6 Q. Maybe it's the thoughts that 7 I'm getting confused on. What if a case report 8 form said life just doesn't seem worth living to 9 me, versus I'm going to kill myself tomorrow. Do 10 you follow the distinction I'm drawing? 11 A. Uh-huh. An expression of life 12 doesn't seem worth living in the case report 13 form, being conservative would have been counted 14 as a suicidal ideation. 15 Q. Obviously I'm going to kill 16 myself tomorrow would be an expression of 17 suicidal intent? 18 A. That's correct. 19 Q. Now would the clinical 20 research assistant who went to Europe be given 21 these guidelines on what they should use in 22 selecting case report forms or data that might 23 possibly indicate suicidal thinking? 24 A. Clinical research associates Page 329 1 that went to Europe were not to make any 2 decisions on what may or may not be an 3 appropriate case, they were to transmit to 4 Indianapolis all case report forms from the 5 controlled clinical trials carried out in Europe. 6 Q. Regardless of whether or not 7 suicidality was expressed? 8 A. That is correct, that's my 9 recollection. 10 Q. Are you saying that the 11 clinical research assistants were just there to 12 physically pick up the case report forms? 13 A. And assist in having them 14 translated, in collecting data, yes, they were 15 not there as decision makers at all. 16 Q. I understand that, but I 17 thought that they had some function in 18 determining which forms indicated a hit, do you 19 follow what I'm saying, and then the forms were 20 brought back to you physicians, and it was the 21 final determination or judgment that was made 22 from a medical standpoint concerning whether or 23 not this was suicidality? 24 A. I don't recall the CRAs being Page 330 1 charged with making a decision on what 2 constituted a hit or not, I do not recall that. 3 Q. All right. So is it your 4 testimony they just brought back all the case 5 report forms? 6 A. That is what I recall, yes. 7 Q. From the European clinical 8 trial experience? 9 A. Right, I do not recall their 10 being charged with deciding on what constitutes a 11 hit. 12 (PLAINTIFFS' EXHIBIT NO. 19 WAS 13 MARKED FOR IDENTIFICATION AND 14 RECEIVED IN EVIDENCE.) 15 MR. COLEMAN: Do you want the witness 16 to read all seventy-four pages of Exhibit 19? 17 MR. SMITH: And memorize it. 18 MS. ZETTLER: For the record, there 19 are not seventy-five pages, there are pages that 20 are culled out. 21 MR. COLEMAN: Oh, I'm sorry. 22 MR. SMITH: No, I do not, Counsel -- 23 you can let him glance through there if you like, 24 but I can certainly point him immediately to the Page 331 1 pages that I'm concerned about. 2 MR. COLEMAN: Do that, and if he wants 3 to read some more, he can. 4 Q. This is the portions of the 5 deposition of Catherine Mesner, Doctor Wheadon. 6 A. Uh-huh, yes. 7 Q. And it's Exhibit 19, and it 8 was taken on August 17, I believe -- October 15th 9 of 1993 in the offices of Baker and Daniels, who 10 are Lilly's lawyers in Indianapolis. Do you 11 recall that she was one of the CRAs that went to 12 Europe to collect this data? 13 A. That's correct. 14 Q. Turn to page two thirty-four. 15 She was asked the question, line six, why were 16 the hits put aside for review by the clinical 17 research physicians. The answer was because it 18 was not our job to review information that we 19 felt was medical in nature and that the 20 physicians needed to make a decision on. She was 21 then asked, do you recall how many hits were 22 collected for review by the CRC, I'm talking 23 about the OUS data. She says, I don't recall a 24 specific number. She was asked can you tell me Page 332 1 generally, her answer was a lot. Then she was 2 asked okay, when you say hits, including 3 information that indicated a suicide, injury or 4 self or injury to others, correct. Answer, or 5 death. Question, death regardless of cause of 6 death. Answer, yes. Question, anything else. 7 Answer, the word overdose or any suspect of 8 overdose. Question, anything else. Answer, in 9 general, anything that would make you lead you to 10 believe that maybe this person did some injury to 11 themselves or had some thoughts to do such. Do 12 you see that? 13 A. Yes, I do. 14 Q. Does that reflect your 15 recollection or do you agree or disagree that the 16 individuals that went to Europe were charged with 17 some responsibility for culling this data to 18 indicate on page two thirty-five, in general 19 anything that would make or lead you to believe 20 that maybe this person did some injury to 21 themselves or had some thoughts to do such? 22 A. As I mentioned, I do not 23 recall the CRAs being responsible for deciding 24 what was or was not a hit, I do not recall that. Page 333 1 Q. But do you have a disagreement 2 with Ms. Mesner when she says that they were 3 collecting data that would indicate injury to 4 themselves? 5 A. I can only repeat that I do 6 not recall the CRAs being charged with the 7 responsibility of deciding what was or what was 8 not a hit, as hit in quotes. 9 Q. Well, do you disagree that the 10 CRAs were going out there and collecting the hits 11 which was any indication of any intent to injure 12 themselves or others, and then it was brought 13 back to you as clinical research physicians to 14 decide whether or not this was indeed 15 suicidality? For instance, the attempt to stab 16 one's self with a plastic butter knife, you gave 17 earlier was not -- was acting out only. That was 18 a medical judgment that you were charged with, 19 but that the CRAs were charged with a judgment 20 simply of does this indicate injury or intent to 21 injure? 22 A. I can only say again that I do 23 not recall the CRAs being charged with making the 24 initial decision of what might be a hit, I do not Page 334 1 recall that. 2 Q. So you could be right or 3 wrong? 4 A. Exactly. 5 Q. Turn to page two thirty-six 6 and see if that helps you. There she's asked 7 concerning the number of hits and she says more 8 than a hundred, but less than a thousand. And 9 I'm paraphrasing, Counsel. But the total number 10 of patients reviewed by them was approximately 11 three thousand. Do you see that? 12 A. In looking through page two 13 thirty-six, the question is how many patients did 14 you review, patients, I'm not talking individual 15 visits. The answer was myself. The question, if 16 you know total. Mister Myers, the group. Ms. 17 Zettler, yes. Answer, approximately three 18 thousand. I'm not really sure what that series 19 of questions is referring to. 20 Q. Okay. Turn to page two 21 forty-four. And I'm not trying to trick you, 22 Doctor, I'm just trying to see if we can get 23 through this and I can refresh your recollection, 24 and maybe we can get you in a position where you Page 335 1 can agree or disagree with Ms. Mesner. 2 A. I understand. 3 Q. Okay. There it's indicating 4 that the number of hits were reduced by less than 5 fifty percent related to homicide or suicide. 6 A. Again, in reading page two 7 forty-four, the question was okay, were they 8 entered into the data base. Answer, oh, yes, 9 everything was entered into the data base. 10 Question, to the best of your recollection, how 11 many of the hits were determined not to be 12 suicide or homicide related by Doctor 13 Heiligenstein and/or Beasley. Answer, I don't 14 recall the number. Question, can you give a 15 percentage, like, say, fifty percent or 16 seventy-five percent. Answer, less than fifty 17 percent. Question, less than fifty percent were 18 pulled as not being related to homicide or 19 suicide, let me make sure I get that straight. 20 The answer is I believe so. 21 Q. Then it says what were done 22 with the hits that were determined to be related 23 to homicide or suicide. It said -- then says if 24 more information was needed, they asked the Page 336 1 affiliate to provide some more information, 2 correct? 3 A. That's correct. 4 Q. So that indicates to me that 5 the physicians at Lilly were reviewing the hits 6 and making a determination as to whether or not 7 this involved a suicidality, is that correct? 8 A. Again, I do not recall the 9 CRAs making that decision, and as you will note 10 on page two forty-four, the answer provided was 11 oh, yes, everything was entered into the data 12 base. 13 Q. I understand that, but you 14 weren't seeing clinical data from a data base, 15 you were seeing the actual clinical report forms, 16 were you not? 17 A. We were reviewing case report 18 forms, that is correct. I do not recall the CRAs 19 being charged with making a decision on what or 20 was not a hit. 21 Q. All right. What was your 22 definition of what a hit was? 23 A. As I mentioned, in reviewing 24 the case report form, any mention indicating Page 337 1 suicidal ideation, behavior, including acts or 2 completed suicides. 3 Q. All right. Do you recall 4 seeing a variety of other types of adverse 5 reactions from the European data such as nausea, 6 nervousness, rash, diarrhea, things of that 7 nature? 8 A. In reviewing a case report 9 form, you will see reports of events of that 10 nature, yes. 11 Q. Was it your understanding, 12 Doctor Wheadon, that all the information that was 13 brought back to you and the other clinical 14 research physicians from Europe was all of the 15 case report form data generated of all adverse 16 events from Europe regardless of the nature of 17 that adverse event? 18 MR. COLEMAN: He answered that 19 question five times. 20 A. And I'll answer it one more 21 time. To the best of my ability to remember, I 22 recall that the case -- all case report forms 23 collected from the controlled clinical trials in 24 Europe were returned to Indianapolis for review. Page 338 1 Q. Okay. Then you clinical 2 physicians, clinical research physicians, 3 reviewed all of these forms to determine whether 4 or not any acts represented suicidality? 5 A. As best I can recall. 6 Q. Doctor Beasley, in his 7 meta-analysis, in connection with the definition 8 of a suicidal act, termed it as any behavior 9 undertaken purposely from which the outcome was 10 likely to be self harm, and where no explicit 11 data suggested that suicide had not been 12 intended. Actions that might be described as 13 suicidal gestures were not excluded. A suicidal 14 act had to have occurred before, during or after 15 the date following the last day of double-blind 16 treatment in compliance with the trial protocol. 17 Would that be the definition -- same definition 18 that was applied to the OUS data? 19 A. Could I read what you're 20 reading from? 21 Q. Sure, it's highlighted. 22 A. As best I can recall, it seems 23 to be in keeping with the OUS data. 24 Q. Why did you exclude acting out Page 339 1 in your review of the OUS data? 2 A. If I recall correctly, acts 3 that did not have clear suicidal -- or intent or 4 injurious intent were excluded, if I recall 5 correctly. 6 Q. What if a patient reported -- 7 was reported on a case report form to have taken 8 twenty aspirin because she was despondent? 9 A. That would be included as a 10 suicidal attempt. 11 Q. Why? 12 A. Patient clearly indicates a 13 suicide ideation with subsequent action of taking 14 twenty aspirin. 15 Q. Even though twenty aspirin 16 ordinarily would not be a lethal amount of 17 aspirin? 18 A. One cannot assume that the 19 patient knew that. 20 Q. All right. Is it your 21 judgment that in connection with intent, you're 22 looking at what the patient intended as opposed 23 to whether there is a medical analysis of whether 24 or not the act used could actually have harmed Page 340 1 the individual? 2 A. That is correct. 3 Q. Is it your recollection that 4 the data that was brought back was the actual 5 clinical report forms or was it working forms, 6 work sheets that were filled out by the CRAs that 7 went to Europe and reviewed this data? 8 A. Both were returned. 9 Q. In every case? 10 A. I cannot recall exactly if 11 work sheets and case report forms for every 12 single case was returned to Indianapolis, but in 13 general both the work sheets and the case report 14 forms were returned to Indianapolis. 15 Q. All right. Are you familiar 16 with Doctor Jan Fawcett? 17 A. Yes, I am. 18 Q. Who is Doctor Jan Fawcett? 19 A. Doctor Fawcett is chairman of 20 psychiatry at Rush Presbyterian Hospital in 21 Chicago. 22 Q. Is Doctor Fawcett a recognized 23 psychiatrist? 24 A. Doctor Fawcett is recognized Page 341 1 as a psychiatrist and as a researcher in the 2 field of psychiatry, yes. 3 Q. And is he knowledgable, known 4 generally knowledgable concerning suicide and 5 anxiety in depression? 6 A. Doctor Fawcett has done 7 research into suicide as well as into depression 8 as well as into anxiety. 9 Q. And has he done research and 10 is knowledgable concerning psychopharmacological 11 treatment of depression? 12 A. Doctor Fawcett has done 13 research on psychopharmacologic treatment of 14 depression, yes. 15 (PLAINTIFFS' EXHIBIT NO. 20 WAS 16 MARKED FOR IDENTIFICATION AND 17 RECEIVED IN EVIDENCE.) 18 Q. Doctor Wheadon, you're 19 certainly free to read this, but I'm only going 20 to ask you, though, about those statements 21 contained on page forty-two under combination 22 therapy, under treatment. 23 A. Okay. 24 Q. But if you feel more Page 342 1 comfortable reading the entire article, feel free 2 to do so. 3 A. If I can just glance through 4 it quickly. 5 Q. Sure. Exhibit 20 is a copy of 6 an article authored by Doctor Jan Fawcett that 7 was published in the Journal of Clinical 8 Psychiatry in November, 1990, is it not? 9 A. In a supplement to the 10 journal, yes. 11 Q. And you recognize the Journal 12 of Clinical Psychiatry as being an authoritative 13 source work recognized by psychiatrists, do you 14 not? 15 A. It's a journal that's read by 16 psychiatrists and is cited in index medicals, I 17 believe. 18 Q. The title of the article is 19 target and treatment in patients with mixed 20 symptoms of anxiety and depression, is it not? 21 A. That's correct. 22 Q. And Doctor Fawcett talks about 23 assessing risk of suicide in depressed patients, 24 does he not? Page 343 1 A. That's correct. 2 Q. And then treatment, does he 3 not? 4 A. That's correct. 5 Q. And specifically under 6 treatment, he talks about combination therapy, 7 does he not? 8 A. That's correct. 9 Q. Specifically he states, quote, 10 suicide prevention is the first consideration in 11 the treatment of major depression with anxiety. 12 Severe anxiety symptoms must be addressed 13 immediately. Few of the antidepressants, 14 especially newer medications, have an early 15 effect on anxiety which may explain that few 16 compliance rate -- or the low compliance rate 17 common to the whole therapeutic class, end quote, 18 does he not? 19 A. He does say that, that is 20 correct. 21 Q. Do you agree with that, 22 Doctor? 23 A. Not in totality, no. 24 Q. Do you agree that Doctor Page 344 1 Fawcett has probably seen more depressed suicidal 2 patients than you have? 3 A. I would agree with that 4 statement, yes. 5 Q. Probably hundreds more, hasn't 6 he? 7 A. Doctor Fawcett has been 8 practicing for some time, that is correct. 9 Q. Well, he's practicing 10 currently, is he not? 11 A. That's correct. 12 Q. And you're not, are you? 13 A. That is correct. 14 Q. Doctor Fawcett continues by 15 saying aggressive treatment with a benzodiazepine 16 anxiolytic is indicated for relief -- for 17 immediate relief of anxiety in patients with 18 major depression if they manifest risk factors 19 for suicide. If the anxiety is severe or if the 20 antidepressant selected causes jitteriness, 21 paren, fluoxetine, or is without sedative 22 properties, paren, desipramine, imipramine, 23 bupropion, antidepressants may take three to six 24 weeks to peak -- reach peak effectiveness, end Page 345 1 quote, correct? 2 A. That is correct. 3 Q. Do you agree that fluoxetine 4 causes jitteriness? 5 A. There have been reports of 6 jitteriness in patients on fluoxetine. 7 Q. And do you agree that if this 8 anxiety is severe with jitteriness, that 9 concomitant benzodiazepines should be prescribed? 10 A. That is not what Doctor 11 Fawcett said exactly. 12 Q. Okay. So do you disagree? 13 A. I do disagree with some of the 14 tenants in his paragraph there, yes. 15 Q. Do you know that Doctor 16 Fawcett is on Lilly's own psychiatric advisory 17 board? 18 A. I'm aware of that, yes. 19 Q. Have you seen Doctor Fawcett 20 in connection with your work at Lilly? 21 A. Yes, I have. 22 Q. And have you discussed these 23 issues with Doctor Fawcett? 24 A. I don't recall discussing Page 346 1 these issues in particular with Doctor Fawcett. 2 Q. Frankly, Doctor Wheadon, don't 3 you consider Doctor Fawcett more knowledgable in 4 this particular area than yourself? 5 A. Doctor Fawcett is an older 6 individual who's been in practice longer. He's 7 entitled to his own opinions as am I. 8 Q. In connection with rendering 9 opinions of a medical nature, isn't the broader 10 clinical base and the longer period of practice 11 helpful in rendering accurate opinions? 12 A. Certainly experience is 13 important in rendering an opinion. 14 Q. That's why you were the chief 15 resident at the V.A. Hospital in Boston and you 16 had residents under you, did you not? 17 A. That is correct. 18 Q. And they were coming to you 19 because you had more experience in treating 20 individuals with particular psychiatric 21 illnesses, correct? 22 A. That's correct. 23 Q. And they were looking to you 24 because you had been -- you had seen more Page 347 1 patients over a longer period of time than had 2 they? 3 A. That's correct. 4 Q. Doctor Fawcett has seen more 5 depressed suicidal patients over a longer period 6 than have you, hasn't he, sir? 7 A. That's correct. 8 Q. In fact, Doctor Fawcett is a 9 recognized expert on suicidality, isn't he? 10 A. Doctor Fawcett has done work 11 in suicidality, that is correct. 12 Q. Do you recognize him, sir, as 13 an expert on suicidality? 14 A. Doctor Fawcett is an expert in 15 suicidality. 16 Q. No, I asked you do you 17 recognize him as an expert in suicidality? 18 A. Yes, I do recognize Doctor 19 Fawcett as an expert in suicidality. 20 Q. Do you recall Professor Lu 21 from Taiwan in his study comparing fluoxetine and 22 Maprotiline in which seven -- six people on 23 fluoxetine and no people on Maprotiline attempted 24 suicide? Page 348 1 A. I do not recall a study by a 2 Professor Lu. 3 Q. Do you recall doing any work 4 in connection with Professor Lu from Taiwan? 5 A. I do not recall having any 6 work associated with Professor Lu of Taiwan. 7 Q. Never heard of Professor Lu of 8 Taiwan? 9 A. I have not heard of Professor 10 Lu of Taiwan. 11 Q. Or anything that he might have 12 done? 13 A. No, I have not. 14 (PLAINTIFFS' EXHIBIT NO. 21 WAS 15 MARKED FOR IDENTIFICATION AND 16 RECEIVED IN EVIDENCE.) 17 Q. Does Exhibit 21 refresh your 18 recollection in connection with Doctor Lu? 19 A. No, it does not. 20 (PLAINTIFFS' EXHIBIT NO. 22 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 Q. Does Exhibit 22 refresh your 24 recollection in connection with Doctor Lu? Page 349 1 A. No, it does not. 2 Q. You just don't remember Doctor 3 Lu? 4 A. I do not remember as well, and 5 you should note, that this was the time -- at the 6 time in which I was leaving Lilly. February, 7 1992 was the date of the first document you 8 showed me concerning Doctor Lu. I left the 9 company in February of 1992, so I do not recall 10 Doctor Lu. 11 Q. All right. In your meeting 12 with the European consultants, you've given -- 13 told us about the German consultant who was 14 Doctor -- 15 A. Professor Moeller, 16 M-O-E-L-L-E-R. 17 Q. Who were the experts from the 18 United Kingdom? 19 A. If I remember correctly, one 20 was Doctor Katona, K-A-T-O-N-A, and I can't 21 recall who the second individual was. 22 Q. Doctor Stuart Montgomery? 23 A. I don't think I met with 24 Doctor Montgomery on that trip. Page 350 1 Q. Did you make more than one 2 trip? 3 A. I've been to the UK a number 4 of times for Lilly, but I don't recall meeting 5 with Doctor Montgomery for that consultant trip. 6 Q. Who was there from Belgium? 7 A. Doctor Cousijns, 8 C-O-U-S-I-J-N-S, if I remember correctly. 9 Q. Is that his first or last 10 name? 11 A. Last name. 12 Q. Do you remember the first? 13 A. No. And I cannot recall the 14 name of the other Belgium psychiatrist. 15 Q. How about France? 16 A. I really cannot recall their 17 names. 18 Q. Do you know an individual by 19 the name of Claude Bouchy or Bouchy, B-O-U-C-H-Y, 20 I believe? 21 A. I don't recall an individual 22 by that name. 23 Q. Do you recall any of the other 24 individuals who were present at the August Page 351 1 meeting with European consultants? 2 A. As I mentioned, I was 3 accompanied by each individual country's medical 4 representative. 5 Q. Okay. Who would have been the 6 medical representative from West Germany? 7 A. I think it was a physician by 8 the name of Jurgenroth. 9 Q. Who from the United Kingdom? 10 A. If I recall correctly, it was 11 Doctor Patrick Keohane? 12 Q. Can you spell that? 13 A. K-E-O-H-A-N-E. 14 Q. From Belgium? 15 A. I think it was Doctor Mark 16 Czarka, C-Z-A-R-K-A. 17 Q. And from France? 18 A. Doctor Beuzen, B-E-U-Z-E-N. 19 Q. Do you know Doctor Hans Weber? 20 A. Yes, I do. 21 Q. In what connection do you know 22 Doctor Weber? 23 A. During the time I was at 24 Lilly, Hans worked in the endocrinology group in Page 352 1 Indianapolis. He also was in the medical group 2 in Germany. 3 Q. Did you ever discuss with 4 Doctor Hans Weber the issue of Prozac and suicide 5 or violent aggressive behavior? 6 A. I do not recall a specific 7 discussion with Doctor Weber about that issue. 8 Q. Do you recall any discussions 9 generally? 10 A. No, I do not recall any 11 general discussions with Doctor Weber on the 12 issue. 13 Q. Do I understand it that there 14 were never any discussions between you, Doctor 15 Leigh Thompson, Doctor Bob Zerbe, Doctor Dan 16 Masica, Doctor John Heiligenstein or Doctor 17 Wernicke, Joe Wernicke, concerning the issue of 18 Prozac and suicidality in Germany? 19 A. I do not recall discussions 20 with any of those individuals on the issue of 21 Prozac and suicidality in Germany. 22 Q. Or any registration problems 23 that Prozac might be having or might have had in 24 Germany by virtue of the suicidality issue? Page 353 1 A. I do not recall discussions of 2 that sort. 3 Q. Now you say that you did meet 4 with Doctor Stuart Montgomery? 5 A. I mentioned yesterday I had 6 met with Doctor Montgomery on several occasions 7 at various meetings. 8 Q. All right. And bear with me, 9 I may have forgotten, I may have asked you this: 10 Did you ever discuss the issue of suicidality and 11 Prozac with Doctor Montgomery? 12 A. Doctor Montgomery was present 13 at a meeting where I was presenting the suicide 14 data, and at that meeting, he did -- he and I did 15 discuss the data. 16 Q. Tell me what those discussions 17 involved. 18 A. If I recall correctly, Doctor 19 Montgomery offered the opinion that the data 20 looked good, that he agreed with the conclusions, 21 and that the issue was one of what he felt was 22 not a real situation, if you will. 23 Q. Did he indicate whether or not 24 he was doing any studies, trials, or research of Page 354 1 any nature concerning this issue? 2 A. As we discussed yesterday, 3 Doctor Montgomery was in the process of carrying 4 out a trial in patients with suicide -- previous 5 suicide behavior, not just depressed patients, 6 that it involved Prozac as well as other 7 antidepressants. He had no knowledge of the data 8 at that time. 9 Q. And you have not since learned 10 anything about what that data might have 11 indicated? 12 A. As I indicated, I have not 13 seen data from that study. 14 MR. SMITH: Let's take a break. 15 (A SHORT RECESS WAS TAKEN.) 16 MR. FREEMAN: At the break, we had a 17 discussion with counsel for the doctor in the 18 Welch case, and in an effort to shorten this, I 19 have assured him that Doctor Wheadon will not 20 appear as a witness in the Welch trial. 21 MR. HARRIS: Nor give expert testimony 22 on the standard of care or any other expert 23 matter, okay. And we're agreeable to that. 24 * * * * * * * * * * Page 355 1 CROSS EXAMINATION 2 BY MS. ZETTLER: 3 Q. Doctor, we met yesterday. My 4 name is Nancy Zettler, and I also represent 5 various plaintiffs who have filed claims against 6 Eli Lilly as a result of injuries to themselves 7 or people in their families. 8 A. All right. 9 Q. I have two follow-up questions 10 to questions that Paul was asking you yesterday 11 and today. Why was it necessary for Lilly 12 employees to go to the European or the OUS 13 affiliates to collect data from the double-blind 14 trials that were conducted there? 15 A. The necessity for that was the 16 following: There were some control trials that 17 had been carried out completely under the 18 auspices of the country affiliate. So there may 19 have been trials in France, case report forms 20 written in French, for example, that were totally 21 directed by, funded by and carried out by the 22 French affiliate, and as such the data resided in 23 the French affiliate. So that was why the 24 necessity was present for Lilly Indianapolis Page 356 1 employees to go to Europe to physically collect 2 those case report forms and that data. 3 Q. Is it your understanding that 4 when a trial is conducted completely under the 5 auspices of a foreign affiliate, as you stated, 6 that protocols and the results of those trials 7 need not be submitted to the FDA? 8 A. If the trial is not done under 9 the IND, there is not a requirement by regulatory 10 mandate that the protocol be submitted to the 11 FDA. 12 Q. How about if it's done under 13 the NDA? 14 A. If it's done under the IND, 15 we're talking about trials that were completed 16 prior to Prozac approval, then that protocol 17 needs -- would by regulatory mandate would need 18 to be submitted to the FDA. 19 MR. COLEMAN: Did you mean to say NDA? 20 THE WITNESS: No, IND. 21 Q. My question was, what about a 22 trial that's done under the NDA in a foreign 23 affiliate? 24 A. I'm not aware that clinical Page 357 1 trials are done under the NDA. The NDA is an 2 application for a drug to be approved for 3 marketing. Clinical trials are done under the 4 IND. I'm not a regulatory expert, so I may be 5 wrong on that designation, but typically a 6 protocol is filed to the IND even after a drug 7 has been marketed for approval, if it's to be 8 used in the United States. 9 Q. How can a study be done 10 outside the United States and not be done under 11 the IND? 12 A. As I mentioned, there are 13 certain areas or certain situations where a trial 14 would be carried out completely within the 15 auspices of -- again using the French as an 16 example -- the French affiliate, where the study 17 is utilizing drugs that are marketed in France, 18 that have been approved in France, as 19 comparitors, that may not be available in the 20 United States. So in a situation such as that, 21 that trial would be carried out completely under 22 the auspices of the French affiliate, and because 23 there would be no use of that data in the United 24 States, it would not be a requirement that that Page 358 1 protocol be filed to the IND. 2 Q. To your knowledge, is Doctor 3 Montgomery's suicide study done under the 4 auspices of the IND or the affiliate in the UK? 5 A. I do not recall the situation 6 with Doctor Montgomery's study. 7 Q. How many of the European 8 double-blind controlled studies that were 9 reviewed were not done under the IND? 10 A. I do not recall. 11 Q. Can you give me a percentage, 12 was it more than half? 13 A. I do not recall. 14 Q. Those studies which were done 15 under the IND but done outside the United States, 16 was that information already here in the United 17 States or did they have to review that 18 information in Europe also? 19 A. Any study done under the IND 20 would have been in Indianapolis and present in 21 the Lilly data base either in Indianapolis or in 22 Erl Wood, which is the European clinical research 23 center. 24 Q. How about the safety Page 359 1 information from those clinical trials that were 2 not done under the IND, would that have to be 3 submitted to the FDA? 4 A. Anything that met the 5 designation of serious adverse event would be 6 submitted to the FDA, yes. 7 Q. I'm not talking about a 8 particular adverse event, I mean as far as the 9 safety reviews that were done in an individual 10 study, would these safety reviews have to be 11 submitted to the IND or NDA? 12 A. Any serious adverse event 13 occurring in a trial world wide would have been 14 reported to the FDA. 15 Q. I'm not talking about an 16 individual 1639 or a CIOMS form or anything like 17 that, okay, I'm talking about at the end of 18 studies, typically efficacy and safety analyses 19 are done, correct? 20 A. Studies not done under the IND 21 required, again, that any serious adverse event 22 would be included in reports to the FDA, safety 23 updates, what have you. 24 Q. I think maybe I'm not making Page 360 1 myself clear. Let's back up a little bit. When 2 a clinical trial is run on a drug, be it Prozac 3 or any other drug, and you're looking at the 4 safety and efficacy of that drug comparing it to 5 placebo or another active compound, the final 6 analysis or the final report of the information 7 gleaned from that trial includes an analysis of 8 the efficacy data as well as the safety data that 9 was collected, correct? 10 A. That is correct. 11 Q. As far as the safety aspect is 12 concerned, the safety data that's collected from 13 a non-IND foreign country clinical trial, the 14 analysis of that safety data, is there a 15 requirement, to your knowledge, that that be 16 submitted to the FDA, regardless of whether or 17 not the study was done under the IND? 18 A. As I mentioned, the 19 requirement is that any serious adverse event in 20 any trial is reported to the FDA. It's a matter 21 of looking at the number of patients that 22 reported nausea, that's not necessarily required 23 to be reported to the FDA for a non-IND trial. 24 Q. So the individual serious Page 361 1 adverse events must be reported to the FDA 2 regardless of where they occur? 3 A. That is correct. 4 Q. But the actual analysis of, 5 say, what was the number of nausea that occurred 6 on the trial as opposed -- on the comparitor as 7 opposed to fluoxetine doesn't necessarily have to 8 be filed as far as you know? 9 A. For a non-IND trial, that is 10 correct. 11 Q. Where did you come to that 12 understanding? 13 A. I beg your pardon? 14 Q. Where did you come to that 15 understanding, that safety analyses of the kind 16 that we were just talking about, apart from 17 individual adverse event, serious adverse event 18 reports, need not be submitted to the FDA when 19 it's done on a non-IND trial? 20 A. That's my recollection of what 21 the review of the regulations by regulatory and 22 legal are. 23 Q. At Lilly? 24 A. At Lilly. Page 362 1 Q. I believe you testified 2 earlier that it was your recollection that the 3 group that went over to the European or the OUS 4 affiliates to collect data on double-blind 5 controlled studies did not look for incidents of 6 violent aggressive behavior or homicidal 7 behavior, correct? 8 A. I testified earlier that the 9 group that went to Europe was not charged with 10 making decisions on what designated a hit or did 11 not designate a hit in terms of the data or the 12 information transmitted back to Indianapolis. 13 Q. They were given guidelines as 14 far as what types of words to look for and things 15 of that nature, were they not? 16 A. I don't recall exactly what 17 guidelines may or may not have been given. I, 18 again, repeat, I do not recall those individuals 19 being charged with deciding what designated a hit 20 and what did not. 21 Q. Okay. But is it your 22 recollection that they were asked to bring back 23 information regarding violent aggressive behavior 24 as well as suicidal behavior? Page 363 1 A. As I previously testified, my 2 recollection is their mandate was to transmit 3 back to Indianapolis all information concerning 4 controlled clinical trials carried out in Europe. 5 Q. Okay. So regardless of what 6 adverse events that occurred during these 7 clinical trials? 8 A. That is correct. 9 Q. Who made the decision that 10 that's the way the data would be collected? 11 A. I do not recall that there was 12 any one person that made that decision. 13 Q. How about the group, what 14 group made that decision? 15 A. If I recall correctly, it 16 would be the group encompassing all of medical. 17 I can't recall a particular group of people that 18 made that decision. 19 Q. Do you have a specific 20 recollection of reviewing clinical report forms 21 for every patient for every visit on the clinical 22 trials that were brought back -- double-blind 23 controlled clinical trials that were brought back 24 in the OUS data gathering project? Page 364 1 A. I do not review every case 2 report form for every patient, every visit, that 3 was brought back from outside the United States. 4 Q. We've had testimony previously 5 that the hits were reviewed by more than one 6 doctor in medical at Lilly, yourself, Doctor 7 Beasley and Doctor Heiligenstein, I believe. Is 8 that your recollection? 9 A. That is correct. 10 Q. And you all reviewed the same 11 groups of hits and your judgments were compared 12 as far as whether or not it actually was a 13 suicidal ideation or suicidal act, correct? 14 A. The process was that two 15 individuals would independently review the cases 16 and arrive at their own decisions concerning what 17 was a hit. If there was disagreement on those 18 cases, a third party would then review the cases 19 additionally to assist with the designation of a 20 hit. 21 Q. Okay. Were the hits or were 22 the clinical report forms ever submitted to 23 somebody outside of Lilly for their opinion on 24 whether or not it constituted a hit? Page 365 1 A. I do not recall outside 2 consultation concerning deciding what was or was 3 not a hit, I do not recall that. 4 Q. Was that same process done for 5 the U.S. clinical trial data? 6 A. Yes. 7 Q. Were you involved in that 8 process also? 9 A. Yes. 10 Q. Was the same criteria used for 11 review of both the U.S. and OUS clinical trial 12 data? 13 A. That's correct. 14 Q. I think you testified 15 yesterday that you believed that the OUS data 16 analysis was not complete prior to Doctor 17 Beasley's article being published, do you recall 18 that? 19 A. I think I testified yesterday 20 that I believe or seem -- I testified that I 21 recalled that Doctor Beasley's manuscript was 22 submitted for consideration for publication prior 23 to the OUS data analysis being completed. 24 Q. Do you know of any reason why Page 366 1 the data analysis could not have been included 2 before the manuscript was published? 3 A. Typically, in the process of 4 considering a manuscript for publication, the 5 manuscript you submit is the manuscript that 6 would be published. Adding new data to already 7 submitted manuscript is not acceptable. 8 Q. Well, lots of times when you 9 submit a manuscript, it isn't published the way 10 you submit it, is it? 11 A. The final published form of a 12 manuscript is based upon editorial comments by 13 the publisher at which time the author or 14 submitter of the manuscript decides whether or 15 not to change the manuscript based on the 16 editorial comment of the publisher. So yes, 17 there may be changes in the final published paper 18 compared to the originally submitted manuscript. 19 Q. Oftentimes statistical 20 analyses of data has to be redone at the request 21 of the publication also, isn't that true? 22 A. There may be a discussion 23 concerning statistical methods used in the 24 manuscript based upon comments by the editors of Page 367 1 a journal, that is correct. 2 Q. Do you know if anybody from 3 Lilly requested that the OUS data analysis be 4 included in the Beasley article? 5 A. I do not recall anyone at 6 Lilly requesting that. 7 Q. To your knowledge has the OUS 8 data analysis ever been published? 9 A. I cannot say that I recall 10 seeing any publication concerning the OUS data. 11 Q. Do you know of a decision made 12 by anybody at Lilly not to publish the data 13 analysis of the OUS data? 14 A. During the time of my tenure 15 at Lilly, I know of no decision at Lilly not to 16 publish the OUS data. 17 Q. When Doctor Beasley's article 18 submitted to the British Medical Journal for 19 publication? 20 A. I do not recall the exact 21 date. 22 Q. Was it before or after the OUS 23 data analysis was submitted to the FDA? 24 A. I do not recall. Page 368 1 Q. Is there an analysis to your 2 knowledge of the OUS data related to violent 3 aggressive behavior? 4 A. As I mentioned earlier, I do 5 not recall an analysis of the OUS data concerning 6 violent or aggressive behavior. 7 Q. When you were analyzing the 8 U.S. and OUS data with regards to the issue of 9 suicidality, were you basing what you were 10 looking for on Doctor Teicher's phenomena that he 11 found in his or reported in his article? 12 A. No, we were not. 13 Q. Why was the determination made 14 to use or to define substantial suicidal ideation 15 as a change from zero to one on the HAM-D three 16 at baseline to three or four? 17 A. If you look at the HAM-D, item 18 three, zero-one essentially refers to no suicidal 19 ideation or, at best, passing thoughts of you no 20 longer existing being better than the present 21 situation. Three or a four refers to frank 22 suicide ideation or significant suicidal 23 behavior. So that, in our mind, was the best 24 approximation in the existing data base of what Page 369 1 Doctor Teicher seemed to be describing. 2 Q. I thought you just said that 3 you weren't looking for Doctor Teicher's 4 phenomena in the review on suicidality? 5 A. My response to your question 6 concerns what we were looking for in our review 7 concerning -- I assumed you were referring to the 8 case report forms, was that we were not looking 9 for phenomena similar to Doctor Teicher. In the 10 analysis involving the HAM-D, item three, we were 11 trying to simulate what it seemed Doctor Teicher 12 was describing in his case reports. 13 Q. How come you didn't do 14 analysis of the HAM-D three to look at 15 suicidality regardless of whether or not it was 16 the kind that Doctor Teicher had reported? 17 A. Other analyses done looking at 18 changes on the HAM-D, item three, looking at mean 19 change on the Hamilton, meaning baseline versus 20 end of study, for the various treatment groups, 21 and looking at shifts, zero to one, one to two, 22 three to four, again, those were done, but the 23 analyses that were designated as best 24 approximating what it seemed that Doctor Teicher Page 370 1 was describing was a zero to one, three to four 2 analysis. 3 Q. Were the analyses that were 4 done to show changes in the HAM-D three reported? 5 A. That was reported to the FDA, 6 yes. 7 Q. How about in the -- either 8 medical or lay media, in journals, for instance? 9 A. The analyses discussed in 10 Doctor Beasley's article in the British Medical 11 Journal is a zero to one, three to four analysis. 12 Q. But to your knowledge, the 13 other analyses that were done that were submitted 14 to the FDA were not reported? 15 A. In terms of other articles, I 16 don't recall their appearing in articles that 17 have been published. 18 Q. Are you familiar with the 19 studies that were included in Doctor Beasley's 20 meta-analysis, generally? 21 A. Generally those studies were 22 the U.S. studies that were double-blind placebo 23 controlled. 24 Q. And they were completed at the Page 371 1 time that the analysis was done, correct? 2 A. These studies had to have been 3 completed as of X date, I don't remember the date 4 exactly. 5 Q. Are you familiar with Doctor 6 Burton Goldstein? 7 A. I know Doctor Goldstein, yes. 8 Q. Are you aware that Doctor 9 Goldstein did a -- or at least began a trial 10 under protocol twenty-seven, which was a 11 comparison -- a multi-center comparison of 12 Imipramine, placebo and fluoxetine and 13 depression? 14 A. I do not recall that. 15 (PLAINTIFFS' EXHIBIT NO. 23 WAS 16 MARKED FOR IDENTIFICATION AND 17 RECEIVED IN EVIDENCE.) 18 A. Do you want to indicate what 19 part of the article you want me to focus on? 20 Q. Yes. Very last page, the 21 enlargement of appendix, table A dash three. 22 MR. COLEMAN: Why don't you ask a 23 question and then -- 24 Q. This Exhibit 23 purports to be Page 372 1 Doctor Beasley's meta-analysis article, correct, 2 a copy of it? 3 A. That's correct. 4 Q. The last page of the exhibit 5 is a table which is actually a continuation of a 6 table that run over a couple of pages describing 7 the studies that were included in the various 8 analyses, correct? 9 A. The title of the table is 10 double-blind clinical trials of fluoxetine versus 11 tricyclic antidepressants versus placebo and 12 depression. 13 Q. And it lists two groups of 14 studies in here, one is under the auspices of 15 sixteen, lists seven individual trials, does it 16 not? 17 A. It lists seven individual 18 investigators in the table, yes. 19 Q. Does it appear to be a 20 multi-center study to you? 21 A. That would be my assumption, 22 yes. 23 Q. How many fluoxetine, placebo, 24 Imipramine depression clinical trials are you Page 373 1 aware of that were performed that were 2 multi-center studies? 3 A. I do not recall. 4 Q. Are you aware that a 5 multi-center placebo, fluoxetine, Imipramine 6 depression trial was submitted to the FDA in 7 support of approval of the drug for marketing 8 here? 9 A. I'm aware that studies 10 involving comparisons to Imipramine and placebo 11 were included in the application for approval, 12 yes. 13 Q. Have you ever seen the FDA's 14 efficacy review on fluoxetine? 15 A. I'm sure I've seen some 16 discussion of the FDA's efficacy review, yes. 17 Q. Do you know Doctor J. Cohn or 18 did you know Doctor J. Cohn? 19 A. I know of Doctor J. Cohn, I do 20 not know Doctor J. Cohn. 21 Q. Were you ever made aware at 22 Lilly that Doctor Cohn's study under the 23 multi-center Imipramine study was not relied upon 24 by the FDA in support of efficacy of the drug? Page 374 1 A. I recall some mention that 2 Doctor Cohn's study was not included in the 3 overall discussion or review of efficacy. 4 Q. Why not? 5 A. I don't recall exactly why 6 not. 7 Q. It was because it was too 8 biased in favor of fluoxetine, wasn't it? 9 A. I do not agree with that 10 statement. 11 Q. What don't you agree with in 12 the statement? 13 A. I'm not aware it was because 14 it was too biased in favor of fluoxetine as you 15 put it. 16 Q. His results, as far as the 17 efficacy of fluoxetine compared to Imipramine or 18 placebo, were that fluoxetine was far superior 19 than either placebo or Imipramine in treating 20 depression, correct? 21 A. I do not recall those study 22 results specifically. 23 Q. Okay. As compared to the 24 other studies that were done under that Page 375 1 multi-center trial? 2 A. I simply recall that Doctor 3 Cohn's results, based on the treatment by 4 investigator analyses of that multi-center study, 5 stood at odds with the other investigators. 6 That's a standard procedure. And because of that 7 treatment by investigator analyses, Doctor Cohn's 8 results were excluded in the overall 9 consideration of that particular trial. 10 Q. So the FDA felt that the 11 results were flawed enough they wouldn't include 12 them in the overall analysis of efficacy in that 13 trial? 14 A. I do not recall the FDA's 15 comments or opinions concerning Doctor Cohn's 16 data. 17 Q. Do you feel it was appropriate 18 to include Doctor Cohn's study in the 19 meta-analysis? 20 A. Beg your pardon? 21 Q. Do you feel it was appropriate 22 to include Doctor Cohn's study that was not 23 reviewed by the FDA in support of efficacy, or at 24 least efficacy in this particular trial, to Page 376 1 include it in the meta-analysis published by 2 Doctor Beasley in the British Medical Journal? 3 A. In your question you've made a 4 couple of false statements. 5 Q. Which ones? 6 A. Doctor Cohn's study was 7 reviewed by the FDA. The situation was, in 8 looking for treatment by investigator 9 interaction, Doctor Cohn's data stood at odds 10 with the other investigators. As a result, that 11 data was excluded in the overall consideration of 12 efficacy. If you recall, the meta-analysis 13 published by Doctor Beasley concerns safety. 14 Doctor Cohn's data was included in the safety 15 data base for the approval of fluoxetine, and as 16 such it was appropriate for Doctor Cohn's data to 17 be included in the meta-analysis concerning the 18 safety of fluoxetine, specifically whether or not 19 there was an association between fluoxetine 20 treatment and suicidal behavior or thinking. 21 Q. What was it about Doctor 22 Cohn's study that was at odds with the other 23 studies? 24 A. As I mentioned, in doing a Page 377 1 treatment by investigator analyses, looking at 2 the efficacy data, Doctor Cohn's results stood at 3 odds with the other investigators, and as a 4 result Doctor Cohn's data for efficacy 5 considerations was excluded from the data -- from 6 the efficacy review for the Imipramine controlled 7 study. 8 Q. What I'm asking you is what 9 was it about Doctor Cohn's studies that was at 10 odds? 11 A. I do not recall specifically. 12 Q. So you don't know if it was 13 that there was something that was flawed about 14 his data or what the reason was that it stood at 15 odds with the other investigators? 16 A. I do not recall specifically 17 what the issue was with Doctor Cohn's data. 18 Q. Would it have been appropriate 19 for Doctor Beasley to include a suspended study 20 in his meta-analysis? 21 A. I do not know what you're 22 referring to. 23 Q. Doctor Goldstein ran a study 24 under protocol twenty-seven just like Doctor Cohn Page 378 1 did, and the rest of the people listed on Exhibit 2 23 under study group sixteen, and his was listed 3 as suspended in the FDA document, it wasn't 4 submitted as a completed clinical trial. Would 5 that be appropriate, if that is the case, for 6 Doctor Beasley to include that study in his 7 meta-analysis? 8 A. I'm not familiar with the term 9 suspended, so I cannot answer your question. 10 Q. It wasn't completed, Doctor. 11 A. Is that your definition of 12 suspended? 13 Q. It's the definition that's 14 used by the FDA in summarizing the studies that 15 were submitted for review. 16 A. If the term suspended refers 17 to the fact that Doctor Goldstein's site did not 18 enroll an adequate number of patients for it to 19 be used in the analysis of efficacy. As I stated 20 previously, Doctor Beasley's meta-analysis was 21 involving safety, Doctor Goldstein's number of 22 patients were included in any safety analyses 23 concerning fluoxetine and its approval to be 24 marketed in the United States, and as such, Page 379 1 including Doctor Goldstein's data and the 2 meta-analysis on whether or not there's an 3 association between fluoxetine and suicidal 4 behavior was appropriate. 5 Q. What was the definition of 6 completed double-blind controlled study that was 7 used in collecting data to analyze for the 8 meta-analysis? 9 A. The trial had to have been 10 completed, meaning all patients had been 11 enrolled, evaluated, and terminated, all data had 12 been collected. 13 Q. When you say all patients had 14 been enrolled, what do you mean? 15 A. The study had ended, all 16 patients that were intended to be enrolled had 17 been enrolled, all patients had been evaluated, 18 all patients had been terminated, no patients 19 were continuing under the protocols. 20 Q. And when you say all patients 21 that had been intended to be enrolled were 22 enrolled, were the number of those patients 23 listed in the protocols? 24 A. Any protocol sets out the Page 380 1 targeted enrollment for the study, that is 2 correct. 3 Q. So under your definition, if 4 Doctor Goldstein's study was suspended because he 5 was unable to enroll the number of patients 6 necessary, it shouldn't have been included in the 7 meta-analysis? 8 A. No, that is incorrect. 9 Q. So where do you make the 10 exception then? 11 A. I'm not making an exception. 12 This is a multi-center trial, meaning there are 13 several distinct individual centers within the 14 context of the trial. The protocol sets out the 15 number of patients that are to be enrolled in the 16 overall trial. Sometimes individual sites don't 17 enroll their total allotment of patients that are 18 intended. 19 Q. So say Doctor Cohn -- 20 A. My definition, as I said, of 21 the studies -- or the definition that was given 22 for studies to be included in Doctor Beasley's 23 meta-analysis, were studies where all patients 24 had been enrolled, had been evaluated and Page 381 1 terminated, the studies had been closed, there 2 was no ongoing work on those studies. Doctor 3 Goldstein's site may not have enrolled adequate 4 numbers to be included in the efficacy analysis 5 was done, they were no longer carrying on the 6 protocol, there were no patients being enrolled, 7 medication was not on site, that study was 8 completed. 9 Q. Was it a requirement that 10 individual final reports needed to be written and 11 submitted to the FDA on these studies for them to 12 be considered completed? 13 A. I do not recall that being a 14 requirement for inclusion in Doctor Beasley's 15 meta-analysis. 16 Q. Who made the decision on what 17 studies would be included in the meta-analysis? 18 A. The decision was made that all 19 studies that had been completed -- 20 Q. I'm not asking you -- 21 A. I am answering your question. 22 Q. No, you're not. I'm asking 23 you who made the decision. I want names, Doctor, 24 I don't want another recitation of what the Page 382 1 decision was, I want the names of the people who 2 made that decision. 3 A. I do not recall. 4 Q. Were you involved? 5 A. I was involved in discussions, 6 I did not make the decision, I do not recall who 7 made the decision. 8 Q. Was Doctor Beasley involved? 9 A. Doctor Beasley was involved in 10 discussions, I do not recall who made the 11 decision. 12 Q. Was Doctor Thompson, Leigh 13 Thompson involved? 14 A. I'm being badgered at this 15 point. 16 Q. I don't think -- 17 MR. COLEMAN: He doesn't recall. You 18 can give him a hundred names, he doesn't recall. 19 MS. ZETTLER: I'm asking him if -- 20 THE WITNESS: I'm being badgered at 21 this point. 22 MS. ZETTLER: -- they were involved in 23 the decision. 24 MR. COLEMAN: He said he doesn't Page 383 1 recall. 2 MR. DOWNEY: He said he doesn't recall 3 who made the decision, she's asking what 4 individuals were involved in the discussions 5 regarding the decision. 6 MR. COLEMAN: Was that your question? 7 MS. ZETTLER: Yes, that was my 8 question. 9 Q. Was Doctor Beasley involved in 10 the discussion? 11 A. Would you like to rephrase 12 your question? 13 Q. Was Doctor Beasley involved in 14 the discussion -- 15 A. Yes. 16 Q. Was Doctor Leigh Thompson 17 involved in the discussion? 18 A. Yes. 19 Q. Was Doctor John Heiligenstein 20 involved in the discussion? 21 A. Yes. 22 Q. How about Allen Weinstein, was 23 he involved? 24 A. I do not recall Allen being Page 384 1 specifically involved, no. 2 Q. How about Dan Masica? 3 A. Yes. 4 Q. Any outside consultants 5 involved in the discussion? 6 A. No. 7 Q. Why did you feel it was 8 necessary or -- when I say you, I mean Lilly in 9 general, to go over to Europe to consult with 10 experts over there on the issue of suicidality? 11 A. The issue of Prozac 12 association, possible association, with suicidal 13 behavior had grown beyond the boundaries of the 14 United States, and as such it was important for 15 us to brief individuals in countries outside the 16 United States on the data that we had collected 17 concerning the question, and also provide or to 18 get their input on what their opinions of the 19 issue and the data were. 20 Q. Was your trip to Europe 21 publicized? 22 A. What do you mean by 23 publicized? 24 Q. Were there articles in the Page 385 1 newspapers about people from Lilly going over to 2 consult with European experts on the issue? 3 A. I'm aware that after my return 4 from Europe, if I recall correctly, there was a 5 small mention that I had visited with European 6 consultants concerning the data. 7 Q. How did the press find out 8 about that? 9 A. I have no idea. 10 Q. Was Doctor Montgomery's 11 suicide study mentioned at the 1991 advisory 12 committee meeting on the issue of fluoxetine and 13 other antidepressants and suicidal ideation or 14 violent aggressive behavior? 15 A. I cannot recall. 16 Q. How about the German 17 government raising the question in the mid-'80s, 18 was that ever mentioned at the advisory committee 19 meeting? 20 A. I do not recall. 21 Q. Doctor Montgomery was a 22 consultant to the committee during that meeting, 23 was he not? 24 A. Doctor Montgomery was present, Page 386 1 yes. 2 Q. How about Doctor Fawcett, did 3 Doctor Fawcett mention that he had, the year 4 before, published an article recommending that 5 patients who were suicidal a concomitant 6 benzodiazepine or sedative be administered to 7 people on fluoxetine? 8 A. I do not recall. 9 Q. Did you know prior to the 1991 10 meeting that Doctor Fawcett had published that 11 article? 12 A. I do not recall when I became 13 aware of Doctor Fawcett's article. 14 Q. Did you become aware of it 15 before today? 16 A. I had seen the article before, 17 yes. 18 Q. Had you ever contacted Doctor 19 Fawcett to discuss that article? 20 A. No, I have not. 21 Q. What is hyperirritability? 22 A. I beg your pardon? 23 Q. Hyperirritability, have you 24 ever heard that phrase before? Page 387 1 A. I'm sure I've heard the phrase 2 hyperirritability. 3 Q. Do you know what it means? 4 A. Not off hand, no. 5 Q. What was done to study the 6 issue of whether or not fluoxetine causes violent 7 aggressive behavior by Lilly? 8 A. The data base of controlled 9 clinical trials completed as of a set date was 10 analyzed looking for any mention of behavior that 11 could be indicative of violent aggressive or 12 homicidal behavior. 13 Q. When you say controlled 14 clinical trials that were completed as of a set 15 date, do you mean all clinical trials world wide 16 or just United States clinical trials? 17 A. Clinical trial data available 18 on trials carried out in the United States. 19 Q. Were they the same clinical 20 trials that were included in Doctor Beasley's 21 meta-analysis? 22 A. I do not recall if they were 23 exactly the same clinical trials. 24 Q. Do you have a problem with Page 388 1 including Doctor Cohn's study of bi-polar 2 disorder patients in Doctor Beasley's 3 meta-analysis as opposed to -- 4 MR. COLEMAN: Does he have a problem? 5 Q. Do you have a criticism of 6 doing that? 7 A. No, I do not. 8 Q. Why not? 9 A. If Doctor Cohn's study of 10 bi-polar patients was included in the 11 meta-analysis, it met the definition set up front 12 for studies to be included. 13 Q. There's a difference between 14 depression and bi-polar disorder, is there not? 15 A. No, not necessarily. 16 Q. Why do you say that? 17 A. Bi-polar disorder includes, as 18 a major component, a depressive phase. So 19 patients with bi-polar disorder may at any period 20 of time have what meets criteria for a major 21 depressive episode with the core symptoms that 22 define a major depressive episode. So from that 23 perspective, depression is not necessarily 24 distinctly different from bi-polar disorder. The Page 389 1 distinguishing characteristic is that patients 2 with bi-polar disorder have also episodes or 3 periods of mania. 4 Q. To your knowledge, in Doctor 5 Cohn's study on bi-polar disorder and the use of 6 fluoxetine, did the patients have to be in a 7 depressive phase at the time they were entered 8 into the study? 9 A. If I recall correctly, 10 patients were in a depressed phase in that study. 11 Q. If the clinical report forms 12 for the OUS clinical trials that were looked at 13 by the group from Lilly that went to the 14 affiliates were all sent back to the United 15 States, why did you need to send somebody over 16 there? 17 MR. COLEMAN: I think that question, 18 very question, has been asked and answered. 19 MS. ZETTLER: If it was, I apologize, 20 but I didn't hear the answer. 21 A. Would you repeat the question, 22 please? 23 Q. Sure. If all the clinical 24 report forms for the clinical trials that were Page 390 1 reviewed by the group that went from Indianapolis 2 to the affiliates, on the OUS data-gathering 3 project, if all the clinical report forms were 4 sent back to the United States, why did you need 5 to send anybody over there to review them in the 6 first place? 7 A. The affiliate offices are 8 manned by relatively speaking small staffs. This 9 was a very large undertaking for a number of the 10 affiliate offices, and as such it was requested 11 that assistance be provided by Indianapolis. So, 12 as I discussed, clinical research associates from 13 Indianapolis were sent to Europe to undertake 14 this task. 15 Q. The task was to collect the 16 serigraphs and bring them back to the United 17 States? 18 A. That's correct. 19 Q. Catherine Mesner testified in 20 her deposition that they were sent over there 21 with work sheets upon which they were to record 22 information about patient visits from the CRFs, 23 and that they were not told to bring back the 24 CRFs. Do you have any recollection of what she's Page 391 1 talking about? 2 A. As I mentioned earlier, I do 3 recall that work sheets and case report forms 4 were returned to Indianapolis. 5 Q. Catherine Mesner also 6 testified in her deposition, and I believe Laura 7 Fludzinski also, that they were given guidelines 8 to look for certain words and phrases as well as 9 certain increases or decreases in HAM-D three or 10 major scores, and they were to pull those 11 particular patient visits as hits to be submitted 12 to the physicians for review. Do you have any 13 recollection of that whatsoever? 14 A. I will repeat for the last 15 time, I do not recall the CRAs that were sent to 16 Europe from Indianapolis being given the mandate 17 to decide what constituted a hit and what did 18 not. 19 Q. To your knowledge was any of 20 this procedure ever rendered or reduced to 21 writing, either what they were sent over there to 22 do as far as collecting the information or what 23 you were to look at to review, anything having to 24 do with the OUS data-gathering project, was it Page 392 1 ever reduced to writing? 2 A. I do not recall. 3 Q. Was Doctor Hans Weber working 4 in Indianapolis when you left the company in 5 1992? 6 A. I do not recall exactly where 7 Doctor Weber was physically located at the time I 8 left the company in 1992. 9 Q. Do you know why Doctor Weber 10 was brought over to the United States to work in 11 Indianapolis for a period of time? 12 A. I was not a part of that 13 decision. 14 Q. That's not my question. Do 15 you know why? 16 A. I do not know why, and I was 17 not a part of that decision. 18 Q. Are you familiar with the time 19 frame in which a final report on an IND study 20 must be submitted to the FDA upon completion of 21 the study, if any? 22 A. I do not know that there is a 23 required time frame for submission of a final 24 report of a completed study to the FDA. Page 393 1 Q. How do you know that the MSSIR 2 suicidality scale was used in clinical trials if 3 you had left at the time they started using it? 4 A. I recall discussions of 5 utilizing the MSSIR, the Modified Suicide 6 Ideation Scale, in trials at the time that I was 7 at Lilly just prior to leaving. 8 Q. Do you know if in fact the 9 scale was ever used in any of those trials? 10 A. I recall seeing protocols with 11 the MSSIR designated to be included in the 12 trials. 13 Q. Are you familiar with Ivan 14 Miller? 15 A. I beg your pardon? 16 Q. Do you know Doctor Ivan 17 Miller? 18 A. If I recall correctly, Doctor 19 Miller is a consultant that was used on creating 20 the Modified Suicide Ideation Scale. 21 Q. Are you aware that Doctor 22 Miller performed a study to validate that scale 23 on behalf of Lilly? 24 A. I'm aware that discussions Page 394 1 were held with Doctor Miller concerning 2 validating the MSSIR, yes. 3 Q. Do you know whether or not 4 that study was begun before you left the company? 5 A. I do not. 6 Q. Are you aware that Lilly is 7 now using the Adult Suicidal Ideation 8 Questionnaire in some of their studies? 9 A. I'm not aware of that. 10 Q. Do you consider the Adult 11 Suicidal Ideation Questionnaire or the MSSIR a 12 more appropriate scale to use in the clinical 13 trials? 14 A. I have no opinion on that. 15 Q. Do you consider the MSSIR more 16 or less appropriate as far as a rating of 17 suicidality than the HAM-D, item three? 18 A. It depends on the purpose of 19 the trial that's being undertaken. 20 Q. In what situation would the 21 MSSIR be more appropriate? 22 A. If the trial is specifically 23 looking for or trying to define a phenomena of an 24 increased obsessive suicidal ideation of the type Page 395 1 described by Doctor Teicher, then the MSSIR would 2 be more appropriate than the Hamilton, item 3 three. 4 Q. Why is it that Lilly is 5 focused on Doctor Teicher's phenomena as opposed 6 to focusing on suicidality in general? 7 A. I don't think Lilly is focused 8 on Doctor Teicher's phenomena in exclusion of 9 focusing on suicidality in general. 10 Q. Why did they go to the trouble 11 of developing a scale that in your opinion would 12 be more appropriate to look at or look for Doctor 13 Teicher's phenomena? 14 A. As has been discussed in 15 previous testimony by myself, and I suppose 16 others, I don't know, the data presented was felt 17 to adequately answer the question from a 18 scientific perspective that Prozac does not cause 19 increase in suicidal behavior or thinking. 20 However, Doctor Teicher and others have said 21 well, this really doesn't answer the question 22 about this rare type phenomena that Doctor 23 Teicher described in his series of case reports. 24 As a result, the MSSIR was developed as an Page 396 1 attempt to try and capture this phenomena if such 2 thing does exist. 3 Q. When you say Doctor Teicher 4 and others have said this does not answer the 5 question about this rare type of suicidality, 6 what do you mean by this? 7 A. The analyses that have been 8 carried out under Lilly clinical trial data base. 9 Q. Like Doctor Beasley's 10 meta-analysis? 11 A. Like Doctor Beasley's 12 meta-analysis. 13 Q. Doctor Teicher reported in his 14 article that he had found that this phenomena was 15 occurring in three point five percent of the 16 patients. Would three point five percent be a 17 significant number for a phenomena? 18 A. I don't quite understand your 19 question. 20 Q. In other words would that mean 21 that the phenomena -- is three point five percent 22 incidence rate rare or is it common, the actual 23 three point five percent rate itself? 24 MR. COLEMAN: Are you asking is it Page 397 1 rare to find three point five percent? 2 Q. No, is it considered rare, is 3 three point five percent incidence in a 4 population considered rare? 5 A. If I recall correctly, as I 6 mentioned yesterday, the three point five percent 7 rate was based on what we view as an incorrectly 8 arrived at denominator. So I cannot comment on 9 the three point five percent rate in Doctor 10 Teicher's article. If you're asking me whether 11 or not three point five percent in and of itself, 12 as a percentage, is rare or common, the 13 designation of rare by FDA mandate, if I recall 14 correctly, falls within one in a hundred to one 15 in a thousand. Or -- I can't remember exactly 16 the definition, I have to review that. 17 Q. One in a hundred to one in a 18 thousand is rare? 19 A. If I recall correctly. 20 Q. Isn't one in a hundred 21 frequent? 22 A. I don't think so. 23 Q. Do you have a problem with 24 doctors in the United States being given the Page 398 1 information that was given to the German patients 2 in the package insert that you discussed with 3 Paul yesterday? And you can take a look at it 4 again if you like. 5 MR. COLEMAN: I think it was covered. 6 A. I think I covered that in more 7 than entirety yesterday. 8 Q. I don't think we were talking 9 about whether or not the patients here should get 10 that same information, I don't believe -- 11 MR. COLEMAN: He went into a whole 12 discussion about whether the FDA let it happen or 13 not happen, and the next series of questions 14 involved whether the doctors should have 15 information. I think that was covered. 16 MS. ZETTLER: I disagree. 17 Q. Would you answer for me one 18 more time, Doctor, if that's true? 19 A. As my counsel has pointed out, 20 I feel that I've adequately answered that 21 question. 22 Q. Your counsel can instruct you 23 not to answer the question if he feels that it's 24 become abusive, you don't have the right to Page 399 1 decide whether or not you're going to answer a 2 question, Doctor, you're here under subpoena. So 3 please patronize me and answer it one more time. 4 A. As my counsel has pointed out, 5 I feel that question has been answered 6 adequately. If you'd like, the court reporter 7 can read you my answer from yesterday. 8 Q. Doctor -- 9 MR. COLEMAN: That really isn't your 10 job, that's my job, but I will be happy to 11 instruct you. I believe it has been asked and 12 answered at least three times. It's not my 13 general practice to instruct a witness not to 14 answer the fourth or fifth or sixth, it's my 15 general practice to ask the lawyer to consider 16 withdrawing the question. If you insist that the 17 question wasn't asked yesterday, if that's your 18 position, I'm not going to ask the court reporter 19 to go back into the transcript and I'll let the 20 doctor answer the question again, but I believe, 21 and I'm asking you to consider, that this 22 question was asked at least three times. 23 MS. ZETTLER: I did, I considered 24 that, and I've looked over my notes which I took Page 400 1 scrupulously yesterday and I noted that that 2 question had not been asked. 3 MR. COLEMAN: I'm not going to argue 4 with you. David, answer the question again. 5 A. Would you repeat the question, 6 please. 7 Q. Do you have a problem with 8 doctors here in the United States being given the 9 information that was included in the most recent 10 copy of the prescribing information or the 11 information that patients in Germany get with 12 regards to suicide risk patients, doctors here 13 getting that information? 14 MR. COLEMAN: You're looking at 15 exhibit number what? 16 MR. SMITH: Exhibit 8. 17 MR. COLEMAN: Your question is does he 18 have a problem with physicians obtaining the 19 information that is contained in Exhibit 8? 20 MS. ZETTLER: Right, regarding risk 21 patients who pose a suicidal risk. 22 MR. FREEMAN: I object to the form of 23 the question because it assumes a fact not in 24 evidence, it doesn't show that the physicians in Page 401 1 the U.S. were given substantially the same 2 information in the package insert. 3 MS. ZETTLER: Joe, show us all the 4 information and maybe we can all go home early, 5 okay. 6 Q. Do you have a problem with 7 including this statement or similar statement 8 that is listed in Exhibit 8 under risk patients 9 that pose a risk of suicide in the package insert 10 to inform doctors here in the United States of 11 that possibility? 12 A. In light of the fact that a 13 similar statement does exist in the prescribing 14 information for Prozac in the United States, I 15 have no problem. 16 Q. What similar statement? 17 A. If you'd like to give me a 18 Prozac package insert, I'll read it to you. 19 Q. Sure. This is a 1990 package 20 insert, Doctor, it's the only one I have with me. 21 Would that be sufficient, do you think? 22 A. We can give that a try. 23 (PLAINTIFFS' EXHIBIT NO. 24 WAS 24 MARKED FOR IDENTIFICATION AND Page 402 1 RECEIVED IN EVIDENCE.) 2 Q. Okay. 3 A. On page -- 4 Q. I'm sorry, Doctor, I wanted to 5 get what exhibit we were on. 6 A. I don't really have a page 7 number, but in Exhibit 24, which is a copy of the 8 1990 prescribing information for Prozac, I don't 9 have a page number, but under precautions, the 10 precautions section, under this section titled 11 suicide, the statement reads: The possibility of 12 a suicide attempt is inherent in depression and 13 may persist until significant remission occurs. 14 Close supervision of high risk patients should 15 accompany initial drug therapy. Prescriptions 16 for Prozac should be written for the smallest 17 quantity of capsules consistent with good patient 18 management in order to reduce the risk of 19 overdose. 20 Q. Where does it say in that 21 passage that Prozac is not generally sedating? 22 MR. COLEMAN: Read the question back, 23 please. 24 (THE COURT REPORTER READ BACK THE Page 403 1 REQUESTED TESTIMONY.) 2 A. It does not make the statement 3 in the passage that I read that Prozac is not 4 generally sedating. 5 Q. Where in the package insert 6 does it say that, 1990 package insert? 7 A. The statement is listed under 8 the precautions section, first line general, 9 anxiety and insomnia. Anxiety, nervousness and 10 insomnia were reported by ten percent to fifteen 11 percent of patients treated with Prozac. 12 Q. So you take that to mean that 13 this is saying that Prozac is not generally 14 sedating? 15 A. Yes. 16 Q. Where does it say in the 17 package insert that taking an additional sedative 18 may be necessary if you have a patient who is at 19 risk of suicide? 20 A. Such statement, that being 21 taking additional sedative may be necessary in 22 patients at a risk of suicide, does not appear 23 verbatim in the package insert that you've handed 24 me. Page 404 1 Q. How about some of the other 2 passages, like the passage you just read, about 3 anxiety, nervousness and insomnia translating 4 into Prozac not being generally a sedative, can 5 you point me to another passage in here which you 6 would interpret as meaning that concomitant 7 sedative or additional sedative may be necessary 8 in patients who are a risk of suicide? 9 A. I do not recall such section. 10 Q. How about additional sedative 11 possibly or maybe being necessary in cases of 12 extreme sleep disturbance or excitability, does 13 that appear in the 1990 package insert? 14 A. Your question again was? 15 MS. ZETTLER: Read it back. 16 (THE COURT REPORTER READ BACK THE 17 REQUESTED TESTIMONY.) 18 Q. The U.S. package insert for 19 1990. 20 A. That exact wording, I do not 21 see in the package insert you handed me. 22 Q. How about language which you 23 interpret to mean that in cases of extreme sleep 24 disturbance or excitability, an additional Page 405 1 sedative may be required? 2 A. I do not see language that I 3 would say says exactly that. 4 Q. Anything close? 5 A. Not specifically, no. 6 MS. ZETTLER: Let's take a break. 7 (A SHORT RECESS WAS TAKEN.) 8 Q. Doctor, can you point for me 9 in the 1990 U.S. package insert any language that 10 implies that if you have a patient who is a risk 11 of suicide, you may want to consider a 12 concomitant sedative along with fluoxetine? 13 A. No, I cannot. 14 Q. Has anyone from Lilly ever 15 criticized your work that you did with Lilly? 16 A. Not that I'm aware of. 17 Q. Has anybody ever been critical 18 of, say, like your temper, say you had a bad 19 temper or short temper? 20 A. Not that I'm aware of. 21 Q. Have you ever had occasions to 22 get into arguments, other than the normal 23 scientific debates, with any other Lilly 24 employees? Page 406 1 A. Not that I'm aware of. 2 Q. Were the double-blind 3 controlled depression studies structured to look 4 at the issue of violence, violent aggressive 5 behavior in any way? 6 MR. COLEMAN: That has to have been 7 asked ten times. 8 A. Repeat your question, please. 9 Q. Sure. Yesterday you talked 10 with Paul at length about whether the 11 double-blind controlled Prozac depression studies 12 were appropriate for analyzing suicidality or 13 emergent suicidality in patients, in other words 14 could they be used to look at that issue. In 15 your opinion were the studies, the double-blind 16 controlled studies that were conducted by Lilly 17 on Prozac for depression structured in such a way 18 that you could look for the phenomena of the 19 emergence of violent aggressive behavior? 20 A. Yes. 21 Q. Okay. What ways could you 22 look at those studies and investigate the 23 emergence of violent aggressive behavior? 24 A. Looking for reports while on Page 407 1 treatment, treatment being Prozac, comparitor 2 agent or placebo, of acts indicative of 3 aggressive -- 4 (DISCUSSION OFF THE RECORD.) 5 THE WITNESS: Could you read the 6 question back and I'll start over. 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED TESTIMONY.) 9 A. As has been mentioned, 10 utilizing the data base consisting of the 11 controlled double-blind clinical trials and 12 assessing them for the occurrence of acts 13 indicative of violent aggressive or homicidal 14 behavior in the various treatment groups, Prozac, 15 active comparitor or placebo. 16 Q. How about any of the scales 17 that were used, could you look at those, like for 18 instance the HAM-D three for suicidality, are 19 there any items on the HAM-D three or any items 20 or scales, including items that would be looked 21 at to judge whether or not somebody is becoming 22 violent aggressive? 23 A. Not included as standard 24 instruments in those studies? Page 408 1 Q. Were you involved in reviewing 2 the data base for violent aggressive behaviors? 3 A. No, I was not. 4 Q. Are you familiar with the 5 criteria that was used to decide whether or not 6 an incident was indicative of violent aggressive 7 behavior? 8 A. I recall the criteria being of 9 a general nature, the general criteria being that 10 acts had to have been outwardly directed and of 11 an aggressive or violent nature, including 12 homicidal acts. 13 Q. Is it fair to say that people 14 who attempt suicide or commit suicide are 15 suffering from self-inflicted or self -- 16 self-inflicted violent aggressive behavior? 17 A. No, it's not. 18 Q. What's the difference between 19 suicidality and violent aggressive behavior 20 directed towards another? 21 A. I think the answer there is 22 quite self-evident, but I'll take you through it. 23 Suicide is an attempt by someone -- or attempted 24 suicide is an attempt by someone to take their Page 409 1 own life for various reasons. Violent aggressive 2 behavior, including homicidal behavior, is 3 behavior outwardly directed toward someone or 4 something else. 5 Q. And that behavior can be 6 exhibited for a number of different reasons also, 7 could it not? 8 A. That is correct. 9 Q. Do you know why Doctor Dunner 10 did the peroxetine meta-analysis? 11 A. No, I do not. 12 Q. Were you involved in that 13 project in any way? 14 A. No, I was not. 15 Q. Did Doctor Teicher ever tell 16 you that he would not cooperate with Lilly in 17 setting up a rating scale to look for his 18 phenomena? 19 A. I do not recall having a 20 discussion personally with Doctor Teicher on 21 setting up rating scales to discover his 22 described phenomena as you put it. 23 Q. Did he ever refuse to 24 cooperate with Lilly in defining this phenomena Page 410 1 that he found? 2 A. I do not recall having 3 discussions with Doctor Teicher in which he 4 refused to cooperate with Lilly in any way. 5 Q. How about anybody at Lilly, 6 did they tell you that Doctor Teicher had refused 7 to cooperate with Lilly in any way? 8 A. I do not recall discussions of 9 such. 10 Q. Yesterday I believe you 11 testified that one of the problems or 12 inadequacies with Doctor Teicher's paper is that 13 his patients' phenomena occur in rapid succession 14 or close together, in other words it was patients 15 that he had looked at over a long period of time, 16 correct? 17 A. I do not recall saying that 18 one of the problems with Doctor Teicher's article 19 was that the patients occurred over different 20 spans of time. I recall indicating that in my 21 discussions with Doctor Teicher it was made 22 evident that these patients were patients that he 23 had seen over an extended span of time. 24 Q. Why is that significant, if it Page 411 1 is? 2 A. The question that was put to 3 me was what was the nature of my discussions with 4 Doctor Teicher, and I responded that that was one 5 of the things he pointed out in my discussion 6 with him. 7 Q. Does that hold any 8 significance to you related to the quality of 9 Doctor Teicher's article where he reports these 10 incidents? 11 A. I think it doesn't have 12 anything to do with Doctor Teicher's article 13 other than stating a fact that these patients 14 were seen over an extended span of time. 15 Q. Do you recall what self-rating 16 scales or patient self-rating scales were used 17 generally in depression trials on Prozac? 18 A. Generally, patient self-rating 19 scales were included, and it is the patient 20 global impression, I think that's what it's 21 called, the patient assessment of their 22 improvement. 23 Q. Could the results of those 24 scales or the information gathered by adding Page 412 1 those scales have been used in any way to look at 2 the issue of emergent suicidal ideation? 3 A. No, they could not. 4 Q. Why not? 5 A. The patient global impression 6 asks a question of the patient compared to last 7 week or compared to when you first entered the 8 study, you say you are improved, very much 9 improved, the same, worse, very much worse. It 10 would not assist in assessing specifically 11 suicidal ideation or behavior. 12 Q. What if the person's HAM-D 13 rating had gone up, indicating they had gone 14 down, indicating they were getting better, and on 15 the global rating scale the patient indicated 16 they were getting worse? 17 A. And your question specifically 18 is? 19 Q. Could such a phenomena happen? 20 A. A patient could have a drop in 21 the HAM-D, item three score indicating a 22 lessening of suicidal thought, and have at the 23 same time a global assessment on their part that 24 they were feeling worse, yes, that could happen. Page 413 1 Q. How about a general HAM-D 2 score dropping and the patient saying that -- and 3 their response to the self-rating scale that they 4 were getting worse? 5 A. It's not unusual for an 6 objective assessment to indicate that the 7 symptomatology is improving, however the patient 8 may not, because of being in the throes of the 9 illness, completely appreciate that. So you may 10 indeed see a drop in the overall Hamilton rating 11 scale score, and the patient in his or her own 12 assessment may say that they're not improved, 13 that is a possibility. 14 Q. Besides the patient global 15 rating scale, are there any other scales used 16 that the patients complete on their own without a 17 rater administering it? 18 A. I don't recall. 19 Q. Would you look again at 20 Exhibit 6, Doctor? 21 (WITNESS REVIEWS DOCUMENT.) 22 Q. Point number two on the first 23 page of Exhibit 6 states the BGA stated that 24 there is a disagreement between patients and Page 414 1 doctors' judgment of efficacy. Do you see that? 2 A. Yes, I do. 3 Q. It goes on to say since in 4 their opinion patient's impression is more 5 important, we have to demonstrate correlation 6 between the SCL 58 and HAM-D and CGI -- and PGI 7 responses, correct? 8 A. That's correct. 9 Q. What is the SCL 58? 10 A. The SCL 58 is a symptom 11 checklist that is administered by a clinician and 12 is answered by the patient, so it's a clinician 13 administered instrument. 14 Q. What is a CGI? 15 A. The CGI is a clinical global 16 impression. There are two types of CGI, either 17 severity or improvement. Again, that's the 18 clinician's impression, not the patient's. 19 Q. Would you say that the SCL 58 20 is the patient's impression and not the 21 clinician's? 22 A. The SCL 58 is administered by 23 the clinician by asking the patients questions, 24 as is the Hamilton. Page 415 1 Q. Do you agree with that 2 statement that the patient's impression of 3 efficacy is more important than the doctor's 4 judgment? 5 A. The statement in and of 6 itself, I do not agree with. 7 Q. Why not? 8 A. I think a physician's 9 assessment of efficacy or therapeutic improvement 10 is important, and oftentimes the physician is 11 better able to judge improvement than the patient 12 who is in the throes of the disease. 13 Q. What if it's the patient who 14 is having an adverse reaction to a medication 15 that's being administered to him or her? 16 A. Again, the physician has the 17 training and the experience to help the patient 18 understand the adverse event, the severity of the 19 adverse event, the necessity of continuing to 20 take medication or not. So the physician is 21 crucial in that consideration. 22 Q. Is that true even if the 23 doctor doesn't have all available information 24 about a particular medication? Page 416 1 A. I don't understand your 2 question. 3 Q. Is the doctor in the best 4 position to help a patient through an adverse 5 event they may be suffering on a medication if 6 they don't have all available information 7 regarding that adverse event? 8 A. As compared to the patient? 9 Q. Yes. 10 A. Yes, the doctor is in the 11 better position. 12 Q. Why? 13 A. The doctor is trained to 14 practice medicine, the doctor is trained to hear 15 patient's symptoms and to put them in the proper 16 perspective. The doctor is trained if he does 17 not have adequate information at hand to seek 18 adequate information to adequately assess the 19 situation. 20 Q. Who do you think knows the 21 patient's body better, the doctor or the patient 22 themself? 23 A. Can you repeat the question, 24 please? Page 417 1 Q. Sure. Who do you think knows 2 a patient's body better, the patient themself or 3 the doctor? 4 A. I have no opinion on that 5 question. 6 Q. Why not, you're a doctor, 7 aren't you? 8 MR. COLEMAN: Just ask the question. 9 He's not answering the question you're a doctor, 10 aren't you. 11 Q. Why not? 12 A. I have no opinion on that 13 question. 14 MS. ZETTLER: You're a doctor aren't 15 you should be the easiest question posed to him. 16 MR. COLEMAN: Maybe the easiest, but 17 it's probably the most offensive. 18 MS. ZETTLER: I'll probably agree with 19 you there. 20 Q. Is Prozac recommended as a 21 first-line treatment for depression? 22 A. The package insert prescribing 23 information for Prozac indicates that it's 24 approved -- or it is approved as a treatment for Page 418 1 depression, there is no assignment of first or 2 second line in the package insert for Prozac. 3 Q. If you were to recommend 4 whether or not it should be used as a first or 5 second line, what would your recommendation be? 6 A. I view Prozac as an acceptable 7 choice as a first-line treatment for depression. 8 Q. Why? 9 A. I view Prozac as an acceptable 10 choice as a first-line treatment for depression 11 because it has been shown to be an effective 12 agent in the treatment of depression. It has 13 also been shown to have an acceptable 14 risk/benefit ratio in terms of adverse events. 15 Q. An acceptable risk/benefit 16 ratio? 17 A. Yes. 18 Q. Acceptable to who? 19 A. Acceptable to the Food and 20 Drug Administration evidently. 21 Q. Anybody else? 22 A. Acceptable to the clinicians 23 who use it on a daily basis. 24 Q. Anybody else? Page 419 1 A. Acceptable to the patients 2 that take it on a daily basis. 3 Q. Every single patient? 4 A. No, not every single patient, 5 obviously. 6 Q. Are you surprised that neither 7 Doctor Wernicke nor Doctor Zerbe nor Doctor 8 Weinstein has ever discussed, at least in your 9 presence, the fact that the German government 10 raised the issue of whether or not more people 11 became suicidal on fluoxetine as opposed to other 12 comparitors? 13 A. In light of the fact that 14 discussions with the BGA concerning that issue 15 occurred prior to my employment at Lilly, I am 16 not surprised by that. 17 Q. Don't you think that that 18 would have been relevant to the discussions once 19 the issue was raised here in the United States? 20 A. No, I do not. 21 Q. Why not? 22 A. The issue raised in the United 23 States was addressed by analyzing the overall 24 Lilly clinical trial data base of double-blind Page 420 1 placebo controlled trials completed by a certain 2 date. The question was asked, put to the data 3 base, and was answered in a scientifically 4 rigorous fashion. 5 (PLAINTIFFS' EXHIBIT NO. 25 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 (DISCUSSION OFF THE RECORD.) 9 Q. Have you had a chance to 10 review Exhibit 25, Doctor? 11 A. I have had a chance to flip 12 through it quickly, yes. 13 Q. First page of Exhibit 25 looks 14 like a memo by -- or letter by a B.V. Keitz in 15 Bad Homburg to Robert Thompson and others, 16 including Doctor Weinstein, correct? 17 A. That is correct. 18 Q. And it's dated August 3, 1990, 19 correct? 20 A. That's correct. 21 Q. On this report or the letter 22 it talks about a suicide report for the BGA, and 23 in fact encloses a copy of that report, correct? 24 A. It reads, attached is the Page 421 1 report on suicides and suicide attempts which we 2 submitted to the BGA in December, 1986. 3 Q. Have you seen this report 4 before? 5 A. I have not. 6 Q. Do you think it would have 7 been relevant with regards to the OUS data 8 analysis project to use this report, at least 9 make a comparison on what was found in 1986 and 10 what was found in 1990 and '91? 11 A. Can you repeat the question? 12 Q. Sure. Would you have liked to 13 have had this report available to you when you 14 were involved in the OUS data-gathering project 15 and analysis? 16 A. It would not have been 17 necessary for the effort that was underway. 18 Q. To your knowledge has anybody 19 compared the numbers of suicide attempts and 20 suicides listed in this report with the numbers 21 that were found as a result of the analysis that 22 you and your colleagues did? 23 A. I'm not aware of any 24 comparison. Page 422 1 Q. How many incidents of suicide 2 did you and your colleagues find as a result of 3 your review of the OUS data? 4 A. I do not recall. 5 Q. More than ten? 6 A. I do not recall. 7 Q. How about suicide attempts, 8 how many did you find as a result of your 9 analysis of the OUS data? 10 A. I do not recall. 11 Q. Are efficacy analyses on 12 clinical trials done in terms of patient years? 13 A. I don't understand your 14 question. 15 Q. Well, yesterday you were 16 talking about how Doctor Beasley's analysis when 17 you looked at the comparisons by patient years, 18 patient years on the drug exposure rates, that 19 fluoxetine had a lower incidence of suicidal 20 ideation, suicidality and suicide, correct? 21 A. That's correct. 22 Q. Was such an analysis used in 23 the efficacy analyses that were done on the 24 clinical trials that were run on Prozac? Page 423 1 A. Efficacy data is not expressed 2 in terms of patient exposure years. 3 Q. Why not? 4 A. It's a different -- it's like 5 apples and oranges, it's completely different, it 6 doesn't apply. 7 Q. If you could do it with the 8 HAM-D three, why can't you do it with the total 9 HAM-D on an efficacy analysis? 10 A. If you would return to the 11 meta-analysis and read it carefully, the rate of 12 suicide attempts, completed suicides, were 13 expressed in patient exposure years. The HAM-D 14 analysis, the zero to one to three to four 15 analysis, was based on the number of patients or 16 percent of patients that evidenced that change in 17 the Hamilton, it was not based on patient 18 exposure years. 19 Q. Couldn't you have analyzed the 20 number of suicides and suicide attempts by 21 numbers of patients attempting suicide or 22 completing suicide compared to those who did not, 23 such like you did with the HAM-D three? 24 A. Again, you're talking about Page 424 1 variables of a different sort. When you're 2 counting a rate of occurrence, as in the rate of 3 occurrence of a suicidal act or completed 4 suicide, standard procedure is to then look at 5 that rate adjusted for the number of patients at 6 risk and the time for which those patients were 7 at risk. That's called the number of acts per 8 patient exposure year. 9 Q. Is that done with all adverse 10 events that are reported in the package insert, 11 are all those rates adjusted by patient year? 12 A. Not all, no. 13 Q. Why not? 14 A. Because you're talking about 15 different types of adverse events. 16 Q. Why, what's different about a 17 suicidal act, other than the obvious possible 18 outcomes, than between a rash and a suicidal act, 19 as far as incidents? 20 A. Because having nausea, for 21 example, is not expected in a patient with 22 depression. Suicidal acts are a part of the 23 disease process of depression, and as such 24 looking at adjusted rates based on patient Page 425 1 exposure year, placebo active treatments, Prozac, 2 is completely in keeping with scientific rigor. 3 Q. But your pool of patients was 4 not the typical depressed patients, was it? 5 A. That is not correct. 6 Q. Why is it not correct? 7 A. The patients included in 8 clinical trials met DSM-3R's or DSM-3's, 9 depending on when the trials were done, diagnosis 10 for depression. 11 Q. And in most of those studies 12 are exclusion criteria for serious suicidal risk, 13 correct? 14 A. Patients that posed a serious 15 suicidal risk at the time of evaluation for 16 inclusion were excluded by protocol. It did not 17 mean they did not have a history of suicide 18 behavior, it did not mean that they might not 19 have an expression of suicidal behavior during 20 the course of the trial. 21 Q. But if you're taking a cross 22 section of patients at large who are suffering 23 from depression, they are not all going to be 24 represented in the patients who are included in Page 426 1 the clinical trials, correct? 2 A. I don't understand your 3 question. 4 Q. Well, women of child bearing 5 years were excluded from a number of the trials, 6 correct? 7 A. By FDA mandate, that is 8 correct. 9 Q. Regardless of who decided 10 whether or not they be excluded, I'm trying to 11 get your understanding of what the patient 12 population was like generally, okay? 13 A. As I answered, by FDA mandate, 14 women of child bearing potential were excluded. 15 Q. What other exclusion criteria 16 generally was there? We know that women of child 17 bearing years were excluded, and serious suicidal 18 risk patients were excluded. What other 19 exclusion criteria were there? 20 A. In general, patients with 21 serious uncontrolled medical conditions would 22 have been excluded, patients on concomitant 23 psychotropic medications in general would have 24 been excluded. Page 427 1 Q. Some types of concomitant 2 psychotropic medications, correct? 3 A. In general, patients with 4 previously designated allergies to fluoxetine, 5 for example, or other compounds and protocols 6 would have been excluded. 7 Q. Anything else? 8 A. Those are the general 9 exclusions I can recall at the time. 10 Q. What does it mean for somebody 11 to be hypersensitive to fluoxetine? 12 A. It generally means that they 13 have some sort of allergic reaction to 14 fluoxetine. 15 Q. Such as rats? 16 A. Exactly. 17 Q. Any psychological reactions 18 that would be considered hypersensitivity to 19 fluoxetine? 20 A. No. 21 Q. Any other physical reactions 22 that would be considered a hypersensitivity to 23 fluoxetine? 24 A. Pruritis or itching without Page 428 1 appearance of rash would be another example of an 2 allergic reaction. 3 Q. How about neurological 4 manifestations of hypersensitivity to fluoxetine, 5 like for instance movement disorders, tardive 6 dyskinesia, things like that? 7 A. That's not an example of 8 hypersensitivity. 9 Q. Who did you replace as global 10 physician, if anyone? 11 A. There was no one in that 12 position prior to myself. 13 Q. Do you know a Doctor Lou Judd? 14 A. I'm familiar with Doctor Judd, 15 yes. 16 Q. Who is Doctor Judd? 17 A. Doctor Judd is chairman of the 18 department of psychiatry at the University of 19 California, San Diego. 20 Q. He used to be director of the 21 National Institute of Mental Health too, didn't 22 he? 23 A. That's correct. 24 Q. Have you ever discussed the Page 429 1 Prozac suicidality project with anybody at the 2 National Institute of Mental Health? 3 A. I do not recall discussing 4 with anyone at NIMH, the National Institute of 5 Mental Health, a Prozac suicidality protocol. 6 Q. No, project, I didn't say 7 protocol. 8 A. I do not recall specifically 9 discussing with anyone at NIMH a Prozac suicide 10 project. 11 Q. How about Doctor Blumenthal, 12 have you had discussions regarding Prozac and 13 suicidality with Doctor Blumenthal? 14 A. I don't recall specific 15 discussion with Doctor Blumenthal. 16 (PLAINTIFFS' EXHIBIT NO. 26 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 Q. Have you had a chance to 20 review Exhibit 26? 21 A. Yes, I have. 22 Q. Does that refresh your 23 recollection as to whether or not you discussed a 24 Prozac suicidality project with Doctor Blumenthal Page 430 1 or anyone else at the National Institute of 2 Mental Health? 3 A. I do not recall having a 4 discussion with Doctor Blumenthal concerning a 5 Prozac suicidality project. 6 Q. What do you recall discussions 7 with Doctor Blumenthal about? 8 A. I can only recall discussing 9 with Doctor Blumenthal the issue of Prozac and 10 suicidality and the data that we had generated 11 concerning Prozac and suicidality. I do not 12 recall specifically a discussion with Doctor 13 Blumenthal concerning a Prozac suicidality 14 project. 15 Q. When did you have this 16 discussion about the topic of Prozac and 17 suicidality with Doctor Blumenthal? 18 A. I do not recall. 19 Q. What is the context -- what 20 context did you meet with Doctor Blumenthal to 21 discuss this subject? 22 A. I did not physically meet with 23 Doctor Blumenthal, I had a telephone conversation 24 with Doctor Blumenthal. Page 431 1 Q. Did you call Doctor Blumenthal 2 or did he call you? 3 A. She was called by myself. 4 Q. Okay. Why did you call Doctor 5 Blumenthal? 6 A. Doctor Blumenthal is a person 7 that has done research in the area of suicide. 8 Q. What was the purpose of your 9 call? 10 A. As I mentioned, I discussed 11 the data that we had analyzed and collected 12 concerning Prozac and suicide with Doctor 13 Blumenthal. 14 Q. Were you in the habit of just 15 calling people to discuss data without another 16 purpose, Doctor? I mean did you call her, was 17 she involved in a project, was she going to write 18 a paper, was there some reason that she would be 19 interested in this data other than the fact that 20 she had done studies on the issue at the National 21 Institute of Mental Health? 22 A. As I indicated, Doctor 23 Blumenthal is an expert in the area of suicide, 24 and as such we thought it beneficial to have the Page 432 1 advice of someone such as herself concerning the 2 data. 3 Q. Did you ask her to review the 4 data? 5 A. I do not recall if there was a 6 discussion about her specifically reviewing, by 7 her own eyes, the data. 8 Q. Was somebody else to review 9 the data on her behalf? 10 A. I do not recall such. 11 Q. Did she ask for a copy of the 12 data? 13 A. I do not recall. 14 Q. Did she express any opinion 15 during your discussion about the data? 16 A. If I recall correctly, Doctor 17 Blumenthal was reassured by the data I discussed 18 with her. 19 Q. Were you going to hire Doctor 20 Blumenthal as an expert on the subject? 21 A. No. 22 Q. Have you ever heard of a 23 Seicor kit, S-E-I-C-O-R kit? 24 A. I'm familiar with Seicor, Page 433 1 which is a clinical laboratory organization that 2 runs clinical labs for physicians as individuals 3 as well as for clinical trials. 4 Q. When you say like 5 laboratories, you mean do blood work or urine 6 analysis or things of that nature? 7 A. That's correct. 8 Q. In any of the clinical trials 9 on depression with fluoxetine that you're aware 10 of, were patient drug diaries used? 11 A. When you say patient drug 12 diaries, what do you mean? 13 Q. Something that's given to the 14 patient or something that the patient is asked to 15 keep regarding when they took the drug, if they 16 felt anything unusual or if they were getting 17 better, symptomatology, routine, things of that 18 nature? 19 A. I don't recall such, no. 20 Q. Do you recall contacting 21 psychiatrists in early 1990 to field questions 22 from the media regarding Prozac on behalf of Eli 23 Lilly? 24 A. I do not recall personal Page 434 1 contact with psychiatrists to field questions on 2 the issue of suicidality and Prozac, no. 3 Q. Do you recall that being done 4 by anybody at Lilly? 5 A. I recall there being a 6 discussion that psychiatrists in the field were 7 interested to help put the issue of Prozac and 8 suicide in proper perspective, and as such would 9 be willing to work with Lilly. 10 (PLAINTIFFS' EXHIBIT NO. 27 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Have you had a chance to 14 review Exhibit 27? 15 A. Yes, I have. 16 Q. It is a memo to Ed West from 17 you dated February 5, 1990, correct? 18 A. That's correct. 19 Q. And it says, regarding, 20 psychiatrists for media referrals. Have gotten 21 agreement from the following to field questions 22 regarding Prozac from the media, correct? 23 A. That's correct. 24 Q. This doesn't indicate that Page 435 1 these gentlemen or ladies contacted you, does it? 2 A. It doesn't indicate who 3 contacted whom. 4 Q. Doctor Dunner agreed to field 5 questions regarding Prozac from the media? 6 A. Based on the document you 7 handed me, it seems to be the case, yes. 8 Q. Were these people or doctors 9 to contact the media or were they to be referred 10 to by Lilly or other people if the media raised 11 questions about the issue of Prozac and 12 suicidality and violent aggressive behavior? 13 A. My recollection is that as 14 requests were received from the media for persons 15 in the field, meaning clinicians, investigators, 16 in various local media markets, that the media 17 could contact to ask questions of, these were 18 people who agreed to be available to the media in 19 that way. 20 Q. How about a request from, say, 21 Seattle that came into Lilly by the media, would 22 that media request still be referred to Doctor 23 Dunner? 24 A. If the media request asked Page 436 1 specifically for someone local that they could 2 talk to concerning the issue of Prozac and the 3 possible association with suicidality, aggressive 4 behavior, what have you, Doctor Dunner's name 5 would have been given to that person with his 6 agreement. 7 Q. Who are the other three people 8 listed on this exhibit that are blocked out? 9 A. I'm not in an ability to tell 10 you that. 11 Q. To your knowledge did Doctor 12 Fawcett ever act as one of these psychiatrists 13 media representatives? 14 A. I do not recall. 15 Q. Do you recall anybody that 16 acted in such a capacity besides Doctor Dunner? 17 A. I think an additional person 18 may have been Doctor Peter Stokes in New York. 19 Q. Was Doctor Stokes on the Lilly 20 psychiatric advisory panel? 21 A. At some point during my 22 tenure, Doctor Stokes did serve on the advisory 23 panel. 24 Q. To your knowledge were these Page 437 1 people who agreed to field questions from the 2 media on the issue of Prozac all members at some 3 time or another of the advisory panel? 4 A. I do not recall specifically. 5 Q. When you were last with Lilly, 6 did the advisory panel still exist, psychiatric 7 advisory panel? 8 A. At the time of my leaving 9 Lilly, as far as I recall, the psychiatric 10 advisory panel did still exist. 11 Q. Who was on the panel at that 12 time? 13 A. I do not recall specifically. 14 Q. Why don't we do it this way: 15 Besides Doctor Fawcett, Doctor Dunner and Doctor 16 Stokes, do you recall anybody else who at any 17 time served as a member of Lilly's psychiatric 18 advisory panel? 19 A. Doctor Paula Clayton. 20 Q. Okay. Anybody else? 21 A. Doctor Charles Nemeroff. 22 Q. Where is Doctor Nemeroff from? 23 A. Doctor Nemeroff is chairman of 24 psychiatry at Emory University. Page 438 1 Q. Anybody else? 2 A. Doctor James Balinger? 3 Q. Where is Doctor Balinger from? 4 A. Chairman of psychiatry at the 5 Medical University of South Carolina. 6 Q. How about Paula Clayton, I 7 take it Paula Clayton is an M.D.? 8 A. Chairman of psychiatry at the 9 University of Minnesota. 10 Q. How about Doctor Winoker? 11 A. I do not recall Doctor Winoker 12 being on the advisory panel. 13 Q. How about Burton Goldstein, 14 was he ever on the advisory panel? 15 A. Doctor Goldstein has served on 16 the advisory panel. 17 Q. Was he still on the advisory 18 panel when you left Lilly? 19 A. I don't think so. 20 Q. Do you know if Doctor 21 Goldstein is still in Miami? 22 A. I have not had contact with 23 Doctor Goldstein in some years, I'm not sure. 24 Q. Can you think of anybody else Page 439 1 that has served on the advisory panel other than 2 those people you already listed? 3 A. That's the people I remember. 4 Q. How about outside consultants 5 used by Lilly specifically on the issue of 6 suicidality and the use of Prozac. We talked 7 about the European experts that you contacted. 8 Can you give us the names of any of the domestic 9 experts that were used with regards to that 10 issue? 11 A. Doctor Winoker was consulted, 12 Doctor Nemeroff was consulted, Doctor Dunner was 13 consulted, if I recall correctly. 14 Q. How about Doctor Fawcett? 15 A. I cannot recall Doctor Fawcett 16 being consulted. 17 Q. How about John Rush? 18 A. I think Doctor Rush was 19 consulted, yes. 20 Q. J. Amsterdam? 21 A. I do not recall Doctor 22 Amsterdam being consulted. 23 Q. Do you know if Doctor 24 Amsterdam ever served on the advisory panel? Page 440 1 A. I do not recall Doctor 2 Amsterdam serving on the advisory panel. 3 Q. How about the issue of violent 4 aggressive behavior and the use of fluoxetine, 5 what outside consultants were used on that issue, 6 if any? 7 A. I recall Doctor Emil Carcaro 8 being consulted. 9 Q. Anybody else? 10 A. That's all I recall. 11 Q. Do you recall that there were 12 others, but you just don't recall their names 13 now? 14 A. I cannot recall if others were 15 consulted. I do remember Doctor Carcaro. 16 Q. Just going through these lists 17 of people on the advisory panel and people that 18 were consulted with regards to the issue of 19 suicidality and violent aggressive behavior, does 20 this refresh your recollection as to whether or 21 not any of these people were people who were on 22 this list -- 23 A. I do not recall. 24 Q. -- Exhibit 27? Page 441 1 A. Other than Doctor Peter 2 Stokes, who I already mentioned, I don't recall. 3 Q. Okay. 4 (PLAINTIFFS' EXHIBIT NO. 28 WAS 5 MARKED FOR IDENTIFICATION AND 6 RECEIVED IN EVIDENCE.) 7 Q. Have you had a chance to 8 review Exhibit 28? 9 A. Briefly, yes. 10 Q. Do you recognize this exhibit, 11 Doctor? 12 A. No, I do not. 13 Q. First page of the exhibit is a 14 memorandum dated August 20, 1991, correct? 15 A. That is correct. 16 Q. It appears to be a memorandum 17 from a Debbie Harrison to a group of Lilly 18 physicians, one of which is you, correct? 19 A. That's correct. 20 Q. The text of the first page 21 reads, this is a retrospective, paren, and now to 22 be prospective, close paren, study of 23 self-inflicted deaths in the blank region for the 24 period of 1988 to 1990, correct? Page 442 1 A. That's correct. 2 Q. Are you familiar with this 3 study at all? 4 A. I'm not sure what study is 5 being referred to in this document, no. 6 Q. Was there more than one study 7 that was done either by Lilly or anybody else on 8 the issue of self-inflicted deaths and 9 fluoxetine? 10 A. It appears that this is a 11 review of the medical examiner reports in some 12 region. So in that case, there are several 13 reviews of such data that exist, yes. 14 Q. Are you familiar with Doctor 15 Inman? 16 A. I know of Doctor Inman, yes. 17 Q. Could this be Doctor Inman's 18 study? 19 A. I have no way of telling 20 whether it is or isn't Doctor Inman's study. 21 Q. Doctor Keohane is from the UK, 22 correct? 23 A. That's correct. 24 Q. Do you know of anybody else in Page 443 1 England that was doing such a retrospective study 2 as set out in this exhibit? 3 A. There are a number of data 4 bases that exist in the UK, Doctor Inman's being 5 one. There are other data bases that will 6 collect information such as this. 7 Q. Does the fact that this letter 8 is going to Doctor Harrison in Basingstoke help 9 narrow it down any for you as far as which data 10 bases it might be? 11 A. The memo is from Doctor Debbie 12 Harrison, who was based at Basingstoke. 13 Q. I'm sorry, I'm talking about 14 the second page. There's a letter from, looks 15 like, a Ph.D to a Doctor D. Harrison in 16 Basingstoke, do you see that? 17 A. Yes. 18 Q. And does this narrow it down, 19 the fact that this person is conversing with 20 Doctor Harrison at Basingstoke as opposed to 21 maybe Erl Wood or the London affiliate, does this 22 narrow it down for you which data base this might 23 be talking about? 24 A. No, it does not. Page 444 1 Q. Do you have any idea what 2 Doctor Harrison said when she wrote this is a 3 retrospective and now to be prospective study of 4 self-inflicted deaths? 5 A. I have no idea. 6 Q. Would it be possible for them 7 to take this data and present is as a prospective 8 study? 9 A. Obviously if the data was 10 collected over the course of 1988 to 1990, it 11 can't be a prospective study in light of the fact 12 that the memo is dated 1991. 13 Q. Were you aware of any 14 prospective studies that were either conducted or 15 considered by Lilly that are similarly set up in 16 this fashion? 17 A. I'm not aware of such. 18 Q. How about the Rocky Mountain 19 Poison Control Center study, are you familiar 20 with that? 21 A. I'm familiar with the Rocky 22 Mountain Poison Control Center, yes. 23 Q. Are you familiar with the 24 study that was being done in conjunction with Eli Page 445 1 Lilly where data was collected from emergency 2 rooms at selected hospitals across the country to 3 be analyzed with regards to fluoxetine compared 4 to other antidepressants? 5 A. In terms of overdose and 6 suicidality, yes. 7 Q. How about as far as incidents 8 of overdose and suicidality? 9 A. The Rocky Mountain protocol 10 that you referred to on Prozac was intended to 11 assess the overdose fatality of Prozac and other 12 antidepressant drugs. 13 Q. It's been pretty well 14 established that it's very difficult to kill 15 yourself by ingesting only fluoxetine, correct? 16 A. That's correct. 17 Q. Why do a study then? 18 A. The Rocky Mounty Poison 19 Control protocol was initiated shortly after the 20 approval of Prozac. So the purpose of that study 21 was to gather further information to document 22 what you now state as being well known, that 23 Prozac and overdose is less lethal than other 24 antidepressant agents. Page 446 1 Q. It also had a cost 2 effectiveness issue to it, did it not? 3 A. I don't recall that aspect in 4 particular. 5 Q. Were one of the objectives of 6 the study to evaluate the medical costs of 7 treating an overdose of fluoxetine as opposed to 8 treating overdoses of other antidepressants? 9 A. That may have been a part, I 10 don't recall that in particular. 11 Q. Was that study still ongoing 12 when you left Lilly? 13 A. Yes, it was. 14 Q. Do you know how long they 15 planned on running that study? 16 A. I don't recall. 17 Q. Throughout the course of your 18 employment at Lilly, you had occasion to review 19 1639s and working 1639s on adverse events for 20 fluoxetine, correct? 21 A. That is correct. 22 Q. Did you ever have an occasion 23 to assign adverse event terms to adverse events 24 that were reported spontaneously to Lilly? Page 447 1 A. I have assisted in the mapping 2 from an actual term to a preferred term based 3 upon the ELECT dictionary, yes. 4 Q. Explain to me how somebody 5 becoming depressed while taking fluoxetine for 6 depression can be considered an adverse event? 7 A. The event term that's 8 typically used in that situation is lack of 9 efficacy. 10 Q. So would it be incorrect for 11 somebody to assign the event term depression to 12 somebody who suffered a worsening of depression 13 while on fluoxetine for depression? 14 A. It would not be inappropriate 15 necessarily, no. 16 Q. And in what situation would it 17 be appropriate? 18 A. One example may be a patient 19 that initially had the response, and seemingly 20 depression had responded -- or remitted, and 21 subsequently depressive symptoms returned. That 22 might be a situation where the adverse event term 23 might be applied. 24 Q. Isn't it -- Page 448 1 A. I think the issue is -- we're 2 using the term adverse event too generally. You 3 might just use the term spontaneous report, it's 4 a report received by Lilly that is filed using a 5 1639. Typically those are what is termed adverse 6 event, but it may be a report such as the one 7 you're referring to. 8 Q. Well, 1639s -- let me mark 9 this. 10 (DISCUSSION OFF THE RECORD.) 11 (PLAINTIFFS' EXHIBIT NO. 29 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Before you take a look at 15 Exhibit 29, are you aware that at Lilly suicidal 16 ideation was mapped to the event term depression? 17 A. If I remember correctly, the 18 ELECT dictionary may have mapped suicidal 19 ideation to the event term depression, yes. 20 Q. And suicide attempts, using a 21 drug, were mapped to overdose? 22 A. If suicide attempts were 23 involving ingestion of a drug, Prozac and another 24 agent, that would map to overdose. Page 449 1 Q. And there was a category for 2 suicide attempts without drugs, correct? 3 A. Yes. 4 Q. And I think that category is 5 suicide attempt, no drug used? 6 A. If I remember correctly, that 7 may be the term. 8 Q. Why couldn't you use the term 9 suicide attempt, drug used, as opposed to 10 overdose? 11 A. You could use any of a number 12 of terms. The reality is, the term used for 13 suicide attempt involving drug was overdose. 14 Q. Did you have anything to say 15 as far as the mapping of that synonym? 16 A. No, I did not. 17 Q. Did you have any criticism of 18 that? 19 A. No, I did not. 20 Q. Did you feel comfortable 21 mapping suicidal ideation to depression and the 22 worsening of depression to depression? 23 A. Yes. 24 Q. Why? Page 450 1 A. Both are components of the 2 illness of depression. 3 Q. So if somebody's worsening -- 4 depression is getting worse, you automatically 5 assume they're suffering suicidal ideation, is 6 that what you're saying? 7 A. That's not what I'm saying. 8 Q. Wouldn't it have been more 9 precise to map a suicidal ideation to suicidal 10 ideation as opposed to depression? 11 A. Not necessarily. 12 Q. Why not? 13 A. Suicide ideation is a part of 14 the illness of depression, and as such the 15 mapping to depression makes sense. 16 Q. Even if it means mapping other 17 synonyms to the same event term? 18 A. Many different terms were 19 mapped to the same actual -- preferred term. 20 Both the actual and preferred terms are captured 21 in the data base. 22 MR. COLEMAN: I understand there's 23 been an agreement that at 2:00 o'clock this 24 deposition terminates, is that correct? Page 451 1 MS. ZETTLER: I've got a few more 2 questions. If I can have another five minutes, I 3 would appreciate it. 4 MR. HARRIS: I have one or two as 5 well. 6 MR. COLEMAN: One or two questions? 7 MS. ZETTLER: I do only have a few 8 more. 9 MR. COLEMAN: We'll go to 2:05, and 10 that's the end of this deposition. 11 Q. Given the media attention and 12 the questions in the scientific community about 13 the relationship between Prozac and suicide 14 attempts, wouldn't it have been better, more 15 appropriate, to list suicide attempts regardless 16 of the method used as suicide attempts as opposed 17 to trying to list them under overdose? 18 A. No, it would not. 19 Q. How about suicidal ideation, 20 wouldn't it have been more honest to list it as 21 suicidal ideation as opposed to depression? 22 A. No, it would not have been 23 more honest. Both terms, the actual term and the 24 preferred term, are captured. Page 452 1 Q. Have you ever heard of IMS 2 International? 3 A. Yes, I have. 4 Q. Tell me what IMS International 5 is, please. 6 A. My understanding of IMS is 7 that it is a prescription monitoring service. 8 Q. Okay. Funded buy who? 9 A. I have no idea. 10 Q. Has Lilly used IMS 11 International? 12 A. I'm aware that Lilly has used 13 IMS, yes. 14 Q. For what purposes? 15 A. The purpose of establishing 16 the denominators for number of prescriptions for 17 drugs that have been filled, as a way of 18 estimating the number of patients that may have 19 taken any drug. 20 Q. So you can establish a 21 denominator using the IMS information? 22 A. You can attempt to approximate 23 a denominator, not establish. 24 Q. Okay. And they use it in Page 453 1 various ways, like in their publications they use 2 it to try to claim or state a number of people 3 who have been prescribed Prozac up to a certain 4 period of time? 5 A. It is used as one method of 6 estimating the number of patients that may have 7 taken Prozac over a period of time, yes. 8 Q. Is it fairly reliable? 9 A. It's a method, again, for 10 estimating. And as such, it is reasonably 11 reliable, but not definitive. 12 Q. Any other methods for 13 establishing a denominator such as the one we 14 were talking about? 15 A. Other mechanisms for 16 attempting to establish denominators is looking 17 at the actual drug, the gram or kilograms, or 18 what have you, of a drug that has been dispensed, 19 and then making an estimation about the number of -- 20 or the dose per patient that might have been 21 divided into, and then subsequently come up with 22 an estimate for the number of patients that have 23 received the drug. 24 MS. ZETTLER: That's all I have for Page 454 1 right now, thanks. 2 * * * * * * * * * * 3 CROSS EXAMINATION 4 BY MR. HARRIS: 5 Q. Doctor Wheadon, I would like 6 to redirect your attention to your testimony that 7 you gave regarding -- 8 A. For my purposes, can we 9 identify -- 10 Q. I just have one question 11 before I do tell you who I am, and that is I want 12 to point to your testimony regarding 13 presentations you made to psychiatrists and 14 general practitioners that you gave yesterday. 15 Do you remember that testimony? 16 A. Yesterday or today? 17 Q. I'm sorry, this morning. And 18 I want to ask you particularly did all or some of 19 those presentations take place after the 20 publication of the Teicher article in the Spring 21 of 1990? 22 A. When you ask whether all or 23 some, do you mean presentations concerning the 24 suicidality data? Page 455 1 Q. That is correct. 2 A. All of those presentations 3 occurred after the appearance of the Teicher 4 article in February of 1990. 5 Q. And did you continue to give 6 those presentations to psychiatrists and general 7 practitioners up and to and through your 8 departure from Lilly in February of 1992? 9 A. As best I can recall, my 10 giving that presentation did extend to close to 11 the end of my tenure with Lilly. 12 Q. All right, sir. Did you 13 travel from Indianapolis to wherever you were 14 located to various locations around the country 15 to hold the presentations? 16 A. That's correct. 17 Q. Now, I'll get to the business 18 of introducing myself. I'm Robert Harris, and I 19 represent a doctor by the name of Doctor Noe 20 Neaves in Dallas, and he's in the Welch case in 21 which the plaintiffs represented by Mister Paul 22 Smith have sued a clinic and Eli Lilly and the 23 doctor as a result of the death of Carl Welch. I 24 only have a few questions in that regard. Have Page 456 1 you ever reviewed any medical records prepared by 2 Doctor Neaves in any cases? 3 A. I do not recall doing so. 4 Q. Have you ever reviewed the 5 medical records of Carl Welch? 6 A. I do not recall doing so. 7 Q. Do you intend to? 8 A. I have no intention in my 9 present position to do so. 10 Q. So we may assume that you have 11 no opinion regarding the type of care or standard 12 of care given to Doctor Welch by Doctor Neaves? 13 A. Not having seen any of the 14 aforementioned documents, I have no ability to 15 form an opinion. 16 MR. HARRIS: That's all the questions 17 I have. 18 MR. SMITH: No further questions. 19 MS. ZETTLER: No further questions. 20 MR. FREEMAN: No questions. 21 MR. COLEMAN: No questions. 22 MR. MYERS: No questions. 23 MS. LAWS: No questions. 24 MR. DOWNEY: No questions. Page 457 1 MR. BRENNAN: No questions. 2 (THE WITNESS WAS EXCUSED.) Page 458 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, Doctor 6 HEREBY CERTIFY THAT THE FOREGOING TESTIMONY OF 7 DR. DAVID WHEADON 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 28TH DAY OF 19 JUNE, 1994. 20 MY COMMISSION EXPIRES MARCH 10, 1994. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 459 1 2 E R R A T A S H E E T 3 4 STATE OF ) : SS 5 COUNTY OF ) 6 7 I, DR. DAVID WHEADON, THE UNDERSIGNED 8 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 9 OF MY DEPOSITION AND WITH THE CHANGES NOTED 10 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 11 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 12 THE 9TH AND 10TH OF JUNE, 1994 AT THE TIME AND 13 PLACE STATED THEREIN. 14 PAGE NO. LINE NO. CHANGE REASON Page 460 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. DAVID WHEADON 10 11 SWORN TO AND SUBSCRIBED BEFORE ME THIS 12 _____ DAY OF __________, 1994. 13 _____________________________ NOTARY PUBLIC, STATE OF 14 PENNSYLVANIA AT LARGE 15 16 17 18 19 20 21 22 23 24 Page 461 1 CONTINUING DIRECT EXAMINATIONBY MR. SMITH:.........1 2 EXAMINATIONBY MS. ZETTLER:........................59 3 CROSS EXAMINATIONBY MR. HARRIS:..................140 4 COMMONWEALTH.....................................143 5 PLAINTIFFS' EXHIBIT NO. 14.........................3 6 PLAINTIFFS' EXHIBIT NO. 15.........................6 7 PLAINTIFFS' EXHIBIT NO. 16........................15 8 PLAINTIFFS' EXHIBIT NO. 17........................17 9 PLAINTIFFS' EXHIBIT NO. 18........................31 10 PLAINTIFFS' EXHIBIT NO. 19........................39 11 PLAINTIFFS' EXHIBIT NO. 20........................48 12 PLAINTIFFS' EXHIBIT NO. 21........................53 13 PLAINTIFFS' EXHIBIT NO. 22........................54 14 PLAINTIFFS' EXHIBIT NO. 23........................72 15 PLAINTIFFS' EXHIBIT NO. 24........................97 16 PLAINTIFFS' EXHIBIT NO. 25.......................112 17 PLAINTIFFS' EXHIBIT NO. 26.......................119 18 PLAINTIFFS' EXHIBIT NO. 27.......................123 19 PLAINTIFFS' EXHIBIT NO. 28.......................129 20 PLAINTIFFS' EXHIBIT NO. 29.......................135 21 22 23 24 Page 462 1 2 3 4 5 6 7 8 9 Page 463 1 DIRECT EXAMINATIONBY MR. SMITH:........13 2 CONTINUING DIRECT EXAMINATIONBY MR. SMITH:.......283 3 CROSS EXAMINATIONBY MS. ZETTLER:......355 4 CROSS EXAMINATIONBY MR. HARRIS:.......454 5 COMMONWEALTH....458 6 (QUESTION CERTIFIED.).......69 7 (QUESTION CERTIFIED.) ......71 8 (QUESTIONS CERTIFIED.).....127 9 (QUESTION CERTIFIED.)......228 10 PLAINTIFFS' EXHIBIT NO. 1.............100 11 PLAINTIFFS' EXHIBIT NO. 2.............120 12 PLAINTIFFS' EXHIBIT NO. 3.............139 13 PLAINTIFFS' EXHIBIT NO. 4.............145 14 PLAINTIFFS' EXHIBIT NO. 5.............161 15 PLAINTIFFS' EXHIBIT NO. 6.............176 16 PLAINTIFFS' EXHIBIT NO. 7.............184 17 PLAINTIFFS' EXHIBIT NO. 8.............203 18 PLAINTIFFS' EXHIBIT NO. 9.............229 19 PLAINTIFFS' EXHIBIT NO. 10............234 20 PLAINTIFFS' EXHIBITS 11 AND 12........269 21 PLAINTIFFS' EXHIBIT NO. 13............272 22 PLAINTIFFS' EXHIBIT NO. 14............286 23 PLAINTIFFS' EXHIBIT NO. 15............289 24 PLAINTIFFS' EXHIBIT NO. 16............300 Page 464 1 PLAINTIFFS' EXHIBIT NO. 17............303 2 PLAINTIFFS' EXHIBIT NO. 18............321 3 PLAINTIFFS' EXHIBIT NO. 19............330 4 PLAINTIFFS' EXHIBIT NO. 20............341 5 PLAINTIFFS' EXHIBIT NO. 21............348 6 PLAINTIFFS' EXHIBIT NO. 22............348 7 PLAINTIFFS' EXHIBIT NO. 23............371 8 PLAINTIFFS' EXHIBIT NO. 24............401 9 PLAINTIFFS' EXHIBIT NO. 25............420 10 PLAINTIFFS' EXHIBIT NO. 26............429 11 PLAINTIFFS' EXHIBIT NO. 27............434 12 PLAINTIFFS' EXHIBIT NO. 28............441 13 PLAINTIFFS' EXHIBIT NO. 29............448 14 15 16 17 18 19 20 Page 465