1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT 2 DIVISION ONE (1) 3 *-*-*-*-* 4 JOYCE FENTRESS, ET AL. PLAINTIFFS 5 6 VS. DEPOSITION FOR PLAINTIFFS 7 8 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 9 10 11 *-*-*-*-* 12 13 14 DEPONENT: MELVIN PERELMAN, PH.D. 15 16 DATE: MAY 19, 1994 17 18 REPORTER: MARY KATHLEEN NOLD 19 20 *-*-*-*-* 21 22 23 KENTUCKIANA REPORTERS 730 WEST MAIN STREET, SUITE 250 24 LOUISVILLE, KENTUCKY 40202 (502) 589-2273 1 1 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 2 INDIANAPOLIS DIVISION 3 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 4 Litigation ) 5 *-*-*-*-* 6 NO. 91-02496-A 7 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 8 V. ) DALLAS COUNTY, TEXAS ) 9 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 10 *-*-*-*-* 11 NO. 92-14775-E 12 RICHARD HAROLD CROSSETT, JR., ) IN THE 13 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT,) COURT OF 14 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 15 JOCQUETTA ANN CROSSETT, DECEASED ) ) 16 V. ) DALLAS COUNTY, ) TEXAS 17 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 18 PSYCHIATRIC COMPANY, INC. ) D/B/A HCA WILLOW PARK ) 101st JUDICIAL 19 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D ) 20 *-*-*-*-* 21 22 23 24 2 1 NO. A-921,405-C 2 MARIA GUADALUPE REVES ) IN THE INDIVIDUALLY AND AS NEXT ) DISTRICT COURT 3 FRIEND OF GRANT JULIAN REVES ) OF A MINOR CHILD, AND ON BEHALF ) 4 OF THE ESTATE OF CHRISTIAN ) MARIE REVES, DECEASED ) 5 ) V. ) ORANGE COUNTY, 6 ) TEXAS ELI LILLY & COMPANY, DISTA ) 7 PRODUCTS COMPANY, RAVIKUMAR ) KANNEGANTI, M.D., HOSPITAL ) 8 CORPORATION OF AMERICA, A ) TENNESSEE CORPORATION, HEALTH ) 9 SERVICES ACQUISITION CORP., ) A DELAWARE CORPORATION, ) 10 HCA PSYCHIATRIC COMPANY, A ) DELAWARE CORPORATION, TEXAS ) 11 PSYCHIATRIC CO., INC., A/K/A ) AND/OR D/B/A HCA BEAUMONT ) 12 NEUROLOGICAL HOSPITAL, AND HCA) HEALTH SERVICES OF TEXAS, INC.) 128TH JUDICIAL 13 A/K/A AND/OR BEAUMONT ) DISTRICT NEUROLOGICAL HOSPITAL ) 14 *-*-*-*-* 15 16 17 18 19 20 21 22 23 24 3 1 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS COUNTY DEPARTMENT - LAW DIVISION 2 RENATO DI SILVESTRO, Individually) 3 and as Special Administrator of ) the Estate of JOHN DI SILVESTRO, ) 4 Deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91-l-7881 ) 7 ROBERT L. NELSON, et al., ) ) 8 Defendants, ) ) 9 GEORGE MELNICK, M.D., and PETER ) FINK, M.D. ) 10 ) RESPONDENTS IN DISCOVERY.) 11 *-*-*-*-* 12 SUPERIOR COURT OF THE STATE OF CALIFORNIA 13 FOR THE COUNTY OF LOS ANGELES 14 DR. MARIUS SAINES, etc., et al., ) Case No.: ) SC 008331 15 ) Plaintiffs, ) 16 ) vs. ) 17 ) ELI LILLY & COMPANY, a corporation;) 18 DISTA PRODUCTS COMPANY, a Division ) of Eli Lilly & Company; and DOBS 1-) 19 100, Inclusive, ) ) 20 Defendants. ) ___________________________________) 21 *-*-*-*-* 22 23 24 4 1 NO. 93-8792-D 2 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF 3 INDIVIDUALLY AND AS SURVIVORS ) AND STATUTORY BENEFICIARIES ) 4 OF MAY YUN KUNG, DECEASED ) ) 5 VS. ) DALLAS, COUNTY ) TEXAS 6 ELI LILLY AND COMPANY, DISTA ) PRODUCTS COMPANY, AND MONIQUE ) 7 KUNKLE, PH.D. ) 8 *-*-*-*-* 9 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS CIVIL COURT DEPARTMENT 10 EUGENE HUSLIG, AS ADMINISTRATOR ) 11 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 12 HUSLIG, DECEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 13 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 14 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 15 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 16 ) 94 C 192 PLAINTIFFS, ) 17 ) COURT NO. 7 VS. ) CHAPTER 60 18 ) MARY L. BILLINGSLEY, EXECUTOR OF ) 19 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 20 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 21 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 22 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 23 ) DEFENDANTS. ) 24 5 1 CAUSE NO. 93-04911-A 2 LINDA JILL WELCH, CARLINDA WELCH REX, CONNAN ROSS WELCH 3 AND CHAD MICHAEL WELCH, INDIVIDUALLY AND AS SURVIVORS 4 AND STATUTORY BENEFICIARIES OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 5 V. 6 ELI LILLY AND COMPANY, DISTA 7 PRODUCTS COMPANY, NOE NEAVES, M.D., AND MINITH-MEIER 8 CLINIC, P.A. DEFENDANTS 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 6 1 I N D E X 2 MELVIN PERELMAN, PH.D. 3 DIRECT EXAMINATION BY MR. SMITH................ 10 4 WITNESS EXCUSED............................... 250 5 6 PERELMAN EXHIBIT NO. 1......................... 41 PERELMAN EXHIBIT NO. 2......................... 48 7 PERELMAN EXHIBIT NO. 3......................... 54 PERELMAN EXHIBIT NO. 4......................... 64 8 PERELMAN EXHIBIT NO. 5......................... 87 PERELMAN EXHIBIT NO. 6......................... 94 9 PERELMAN EXHIBIT NO. 7........................ 101 PERELMAN EXHIBIT NO. 8........................ 106 10 PERELMAN EXHIBIT NO. 9........................ 129 PERELMAN EXHIBIT NO. 10....................... 136 11 PERELMAN EXHIBIT NO. 11....................... 143 PERELMAN EXHIBIT NO. 12....................... 147 12 PERELMAN EXHIBIT NO. 13....................... 156 PERELMAN EXHIBIT NO. 14....................... 170 13 PERELMAN EXHIBIT NO. 15....................... 179 PERELMAN EXHIBIT NO. 16....................... 200 14 PERELMAN EXHIBIT NO. 17....................... 202 PERELMAN EXHIBIT NO. 18....................... 214 15 PERELMAN EXHIBIT NO. 19....................... 218 PERELMAN EXHIBIT NO. 20....................... 222 16 PERELMAN EXHIBIT NO. 21....................... 230 PERELMAN EXHIBIT NO. 22....................... 235 17 PERELMAN EXHIBIT NO. 23....................... 241 PERELMAN EXHIBIT NO. 24....................... 247 18 19 20 21 QUESTION CERTIFIED............................ 189 22 23 24 7 1 THE FOLLOWING DEPOSITION 2 OF MELVIN PERELMAN, PH.D., WAS TAKEN AT THE 3 OFFICES OF BAKER & DANIELS, 300 NORTH MERIDIAN 4 STREET, SUITE 270, INDIANAPOLIS, INDIANA, 46204, 5 ON MAY 19, 1994; SAID DEPOSITION TAKEN PURSUANT TO 6 NOTICE IN ACCORDANCE WITH THE RULES OF CIVIL 7 PROCEDURE. 8 *-*-*-*-* 9 A P P E A R A N C E S 10 11 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 12 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 13 14 15 PAUL SMITH COUNSEL FOR PLAINTIFFS 16 745 CAMPBELL CENTER 2 8115 NORTH CENTRAL EXPRESSWAY 17 DALLAS, TEXAS 75206 18 19 JOE FREEMAN LAWRENCE J. Myers 20 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 21 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 22 ATLANTA, GEORGIA 30308-3243 23 24 8 1 APPEARANCES (CONTINUED) 2 MARY HUFF ELI LILLY AND COMPANY 3 LILLY CORPORATE CENTER INDIANAPOLIS, INDIANA 46285 4 5 6 BEATRICE M. SMITH COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 7 FRIEND & ASSOCIATES LLP 1301 MCKINNEY, #2900 8 HOUSTON, TEXAS 77010 9 10 BARTON BROWN COUNSEL FOR DOCTOR BILLINGSLEY 11 WALLACE, SAUNDERS, AUSTIN, BROWN & ENOCHS 10111 WEST 8TH STREET 12 PO BOX 12290 OVERLAND PARK, KANSAS 66282 13 14 15 ROBERT L. HARRIS COUNSEL FOR NOE NEAVES, MD 16 SIFFOLD & ANDERSON, LLP 6300 NATIONS BANK PLAZA 17 901 MAIN STREET DALLAS, TEXAS 75202 18 19 20 JOHN BRENNAN MCCARTER & ENGLISH 21 4 GATEWAY CENTER 100 MULBERRY STREET 22 NEWARK, NEW JERSEY 07102-4096 23 24 9 1 MR. MYERS: Do we have 2 the same agreements with respect to the state 3 court cases and the applicability of the MDL 4 protective orders for the other depositions? 5 MR. SMITH: Correct. 6 *-*-*-*-* 7 MELVIN PERELMAN, PH.D., 8 called by Plaintiffs, after having been first duly 9 sworn, was examined and deposed as follows: 10 11 DIRECT EXAMINATION 12 13 BY MR. SMITH: 14 Q State your name. 15 A Melvin Perelman. 16 Q How old a man are you, 17 Doctor Perelman? 18 A Sixty-three. 19 Q Where do you live? 20 A Indianapolis. Would you 21 like the address? 22 Q No, I'm not planning on 23 calling you or coming by, so I don't need your 24 address. How long have you lived in Indianapolis, 10 1 Doctor Perelman? 2 A Indianapolis and Carmel, 3 a suburban community taken together, of the last 4 thirty-seven years would be thirty-one. 5 Q Do you maintain any other 6 residences outside of the Indianapolis area, for 7 instance summer homes? 8 A Davis, California and 9 Tahoe, California. 10 Q Are you a married man, 11 Doctor Perelman? 12 A Yes. 13 Q Children? 14 A Yes. 15 Q Does either your wife or 16 any of your children work for Eli Lilly and 17 Company? 18 A No. 19 Q I assume your children 20 are grown? 21 A Yes. 22 Q Are you currently 23 employed, Doctor Perelman? 24 A No, only a couple of 11 1 board memberships, not including Eli Lilly and 2 Company. 3 Q You say you are not on 4 the board of Eli Lilly and Company anymore? 5 A That's correct, I'm on a 6 couple of other commercial industrial boards, but 7 not Eli Lilly and Company. 8 Q What other boards are you 9 a member of, sir? 10 A Public Service Indiana, 11 which is an electric utility based here in 12 Indiana, and DataChem which is based here in 13 Indianapolis. 14 Q Are those both for profit 15 corporations? 16 A They are. 17 Q And you serve as a Board 18 of Directors by virtue of stock ownership in those 19 corporations? 20 A Yes, I do have stock 21 ownership in both of those. 22 Q Do you still maintain 23 stock in Eli Lilly and Company? 24 A I do. 12 1 Q And you were on the Board 2 of Directors of that corporation for a while, were 3 you not? 4 A Yes. 5 Q And when did you retire 6 from the Board? 7 A December 31, 1993. 8 Q Was that the date that 9 you retired as an employee of Eli Lilly and 10 Company also, sir? 11 A Yes, that's correct. 12 Q And you said you did 13 still own stock in Eli Lilly? 14 A Yes. 15 Q Do you still receive 16 pension profit sharing benefits as a result of 17 your employment with that corporation? 18 A Pension benefits, yes. 19 Q Do you serve as a 20 consultant or in any way render advice to any 21 other corporations or entities, sir, at this time? 22 A No. 23 Q Have you served as a 24 consultant for any other corporation or entity 13 1 since December 31, 1993? 2 A No. 3 Q When did you start your 4 employment with Eli Lilly and Company? 5 A December 17, 1957. 6 Q And did you work for Eli 7 Lilly and Company continuously from December 1958 8 until December 1993? 9 A I did. 10 Q Give me a brief outline 11 of your educational background, Doctor Perelman, 12 beginning with when and where you graduated from 13 high school. 14 A I graduated from high 15 school in Omaha, Nebraska in 1948, and then 16 received a BS in chemistry from Northwestern 17 University in 1952, and then a Ph.D. from Rice 18 University in 1956, and then was an American 19 Cancer Society post-doctorate fellow at the 20 Federal Institute of Technology in Zurich, 21 Switzerland in 1956, 1957. 22 Q And then did you go 23 directly to Eli Lilly and Company when you 24 finished that fellowship? 14 1 A Yes. 2 Q When you received your 3 Ph.D. from Rice University in Houston, Texas, I 4 assume it was in a chemistry related discipline? 5 A Yes, it was organic 6 chemistry again. 7 Q Any particular area of 8 chemistry that you studied when you were with the 9 American Cancer Society as a fellow? 10 A Well, my doctorate work 11 was with steroid hormones and the post-doctorate 12 work related to steroid hormones as related to 13 cancer and particularly breast cancer. 14 Q Have you received any 15 other formal training since you completed your 16 fellowship? 17 A No. 18 Q Have you done any 19 particular studies in neuropsychopharmacology? 20 A No. 21 Q Do you consider yourself 22 knowledgeable in matters of neuropsycho- 23 pharmacology? 24 A No. 15 1 Q Do you consider yourself 2 knowledgeable or have knowledge beyond that of an 3 ordinary Ph.D. chemist with respect to 4 biochemistry? 5 A With respect to 6 biochemistry in general, no. 7 Q How about to 8 neurochemistry? 9 A No. 10 Q Specifically I'm talking 11 about, for instance, Doctor Ray Fuller at Lilly 12 has done extensive work in neurochemistry dealing 13 with serotonin norepinephrine and things of that 14 nature. 15 A Yes. 16 Q Have you done anything in 17 that connection? 18 A None whatsoever. 19 Q Take me, would you 20 please, sir, through the various positions that 21 you've held with Eli Lilly and Company. 22 A I joined as a senior 23 organic chemist. I then went into a three-year 24 training program and worked in the Legal 16 1 Department and in Antibiotic Manufacturing and in 2 Elanco, which is our agricultural subsidiary. 3 After that, I was an Assistant to the Executive 4 Director of Quality Control. 5 Q All right, let me 6 interrupt you. I need to get some dates, and take 7 it in a chronological order. You say you started 8 as a senior organic chemist and then went to a 9 three-year training program and worked in the 10 Legal Department and with Elanco. Was that all 11 during that first 3 years? 12 A Yes, the 3 things that I 13 mentioned -- well, I can give you the times, 1957 14 to 1962 an organic chemist; 1962 to -- actually 15 through 1964, it was short of 3 years, and during 16 that 1962 to '64 period, I worked in the Legal 17 Department, Antibiotic Purification, Antibiotic 18 Manufacturing so to speak, and in Elanco, the 19 agricultural subsidiary. The exact number of 20 months -- roughly an equal period of time. 21 Then for 1964, I was part 22 of that year, a very short time, Assistant to the 23 Executive Director of Quality Control. 24 In 1964 I was transferred 17 1 to England as managing director of the Lilly 2 Research Center. I remained in England until 3 1970. While there, in 1969, I became a vice 4 president of Eli Lilly International Corporation, 5 still retaining responsibility of Managing 6 Director of the Research Center. 7 Q Would 1969, when you were 8 named as a vice president of Eli Lilly 9 International, be the first occasion when you were 10 named as an officer of any of the Lilly 11 corporations? 12 A It would. 13 Q Continue, sir; I'm sorry 14 to interrupt you. 15 A In 1970 I repatriated to 16 Indianapolis as Executive Director of Facilities 17 and Operations Planning. Eighteen months later, 18 probably around 1972, I became Vice President of 19 Developmental Research and Services of the Lilly 20 Research Laboratories. 21 Eighteen months after 22 that, sometime in '73, I became Vice President of 23 Facilities and Operations Planning, and at that 24 time I became an officer of Eli Lilly and Company 18 1 as opposed to the international corporation. 2 Then in December of 1976 3 I became President of Eli Lilly International 4 Corporation, which position I held for ten years 5 until December of 1986, when I became President of 6 the Lilly Research Laboratories and Executive Vice 7 President of Eli Lilly and Company, which position 8 I held until retirement at the end of December of 9 1993. And I believe I'm correct that I went onto 10 the Board in 1976. 11 Q When you say you went 12 onto the Board, you're talking about the Board of 13 Directors of Eli Lilly Corporation? 14 A Eli Lilly and Company, 15 yes, sir. 16 Q What did you do in the 17 legal department back in the '60s? 18 A I was a go-fer, a 19 technical go-fer in the sense that I had no legal 20 training, but it was at a time when they had a 21 considerable amount of need of a captive in-house 22 scientific type because of the nature of some of 23 the work load in legal at the time. It was 24 primarily part of that two-year training program 19 1 and it was my selection to go into legal and 2 spent, I think, about nine months as an aid to the 3 attorneys from the scientific point of view. 4 Q Served sort of as an 5 in-house consultant on scientific matters? 6 A Yes. 7 Q Was Mr. Burns there then? 8 A No, he was probably in 9 elementary school. 10 Q Now, you were in England 11 physically from 1964 to 1970? 12 A That's correct. 13 Q And at that time you were 14 the Managing Director of Lilly Research Center? 15 A Yes. 16 Q I assume where, at Erl 17 Wood? 18 A The first 3 years was up 19 near Liverpool, and we were selecting the property 20 and building Erl Wood, and in 1967 we moved down 21 and occupied Erl Wood. 22 Q In '69 you became the 23 vice president of Eli Lilly International and 24 remained at Erl Wood, is that correct? 20 1 A That's correct. 2 Q Now, are there three 3 separate corporations within Eli Lilly Company at 4 least, but the three I'm interested in would be 5 Eli Lilly International, Lilly Research Labs and 6 Lilly Corporation -- the Lilly Corporation, I 7 guess it would just be two corporations? 8 A Yes, I think technically 9 the Lilly Research Laboratories are a division of 10 Eli Lilly and Company, whereas Eli Lilly 11 International Corporation is legally an entity. 12 Q When you became Vice 13 President of Eli Lilly International, who did you 14 report to, Doctor Perelman? 15 A A gentleman named Robert 16 S. McNeal, who was Executive Vice President of Eli 17 Lilly International Corporation and was based in 18 our European, Middle Eastern, African headquarters 19 in London. 20 Q When you came back to the 21 United States and became Executive Director of 22 Facilities and Operational Planning with -- Lilly 23 Research Labs? 24 A No, Eli Lilly and 21 1 Company. 2 Q Eli Lilly and Company, 3 who did you report to? 4 A Doctor Harold Wiseley, 5 who was Executive Vice President of Eli Lilly and 6 Company. 7 Q And when you became Vice 8 President of Lilly Research Labs, who did you 9 report to? That would have been in '73, correct? 10 A Yes. At that time, 11 Doctor Neal Pettinga, C.W. Pettinga. 12 Q Then for ten years you 13 served as President of Eli Lilly International, 14 correct? 15 A That's correct. 16 Q Were you here in 17 Indianapolis at that time? 18 A Yes, sir. 19 Q And to whom did you 20 report? 21 A Mr. Richard D. Wood. 22 Q And he was Chief 23 Executive Officer and Chairman of the Board of the 24 corporation, I believe, during that period of 22 1 time? 2 A And President, yes. 3 Q And I would assume that 4 from 1976 until your retirement, the only 5 individual that you reported to would have been 6 then Mr. Richard Wood? 7 A No, when I moved to the 8 Research Laboratories position in 1986, I reported 9 to Doctor Earl B. Herr. 10 Q And what was his position 11 at that time? 12 A He was Executive Vice 13 President of Eli Lilly and Company. And to 14 complete the answer to that question, then when he 15 retired and I assumed the Executive Vice 16 Presidency while retaining the presidency of the 17 labs, I reported to Vaughn Bryson for the last 18 couple of years of his tenure. 19 Q That was after Mr. Wood 20 retired? 21 A After Mr. Wood retired. 22 Q Doctor Perelman, we have 23 been introduced, my name is Paul Smith and I 24 represent a number of individuals who have filed 23 1 suit against Eli Lilly and Company by virtue of 2 claims against that corporation because of adverse 3 experiences and reactions that they've had in 4 connection with the drug Prozac, fluoxetine 5 hydrochloride manufactured by Lilly. 6 I'm here today to take 7 your deposition and your deposition will be used 8 as evidence in the trial of these cases. For that 9 reason it's very important that we be 10 communicating together on the right wavelength. 11 If you have any questions concerning the meaning 12 of my questions or if you are unclear with respect 13 to anything that I ask you, please feel free to 14 stop and ask me to rephrase the question and I'll 15 be glad to do so, so we'll have a clear record. 16 Will you do that for me, sir? 17 A I certainly will, thank 18 you. 19 Q Additionally, this is not 20 an endurance contest, so if you need to take a 21 break or in any way change the mode of operation, 22 please, let me know and we'll be happy to 23 accommodate you, sir, all right? 24 A Yes, sir. 24 1 Q Have you had an 2 opportunity to discuss your deposition here today 3 with counsel? 4 A Yes. 5 Q When did you first meet 6 with counsel in connection with giving your 7 deposition? 8 A Monday of this week. 9 Q And how long did that 10 meeting occur? 11 A Oh, let's see, probably 12 about six hours, five or six. 13 Q Have you had any other 14 meetings with counsel since then, since Monday? 15 A Only gathering here a bit 16 before this deposition started. 17 Q Have you reviewed any 18 documents, Doctor Perelman, in connection with 19 giving your deposition today? 20 A No. 21 Q Were you shown any 22 documents by counsel in your meeting on Monday? 23 A No, sir. 24 Q You're going to need to 25 1 give an audible answer as opposed to shaking your 2 head because our court reporter has enough 3 difficulty as it is. 4 When were you first 5 aware, Doctor Perelman, of the compound fluoxetine 6 hydrochloride? 7 A I'm not able to fix a 8 date even with any accuracy the year. It was 9 while I was President of International prior to my 10 returning to the Research Labs, but I can't be 11 precise at all about that. 12 Q So it would have been 13 sometime between 1976 and 1986? 14 A Yes, and closer to the 15 latter part of that ten-year period. 16 Q By the time you became 17 president of Lilly Research Labs, obviously the 18 clinical trials in connection with Prozac were 19 already well underway? 20 A Yes. 21 Q And by 1986, I believe 22 you had already received the approvable letter 23 from the Food and Drug Administration in 24 connection with that product? 26 1 A There was a long lapse 2 between approvable and approved, and I can't say 3 accurately that that would have been the case. 4 Q All right. But by 1986, 5 the NDA and the IND had been submitted to the Food 6 and Drug Administration? 7 A Yes, sir. 8 Q And then the product was 9 approved by the United States Food and Drug 10 Administration in December 1987? 11 A That's correct. 12 Q Would it be safe to say 13 that it was in the 1980's that you first heard of 14 the compound fluoxetine hydrochloride? 15 A I would think so, yes. 16 Q What was the method or 17 manner in which you first learned of Prozac? 18 A I would have to -- that 19 would be into the realm of conjecture. I can't 20 precisely say when or how, through what mechanism 21 I would have first heard of it. 22 Q What was your first 23 understanding of what Prozac was, where it was in 24 development, and things of that nature? 27 1 A Well, my first -- my 2 clear recollection of where I would have heard of 3 it, but I cannot say it was the first time, would 4 have been in a Product Strategy Committee when it 5 will have been reviewed for senior management on a 6 fairly comprehensive basis. 7 Q Do you recall who was 8 responsible for developing the compound at that 9 time? I mean, I understand it was Lilly Research 10 Labs that was conducting the studies. 11 A Yes. 12 Q But who did you 13 understand were some individuals in management 14 that were directly overseeing the development of 15 that product? 16 A In management? 17 Q Yes. 18 A Well, I would have -- 19 Doctor Herr, as President of Lilly Research 20 Laboratories at the time, Doctor Leigh Thompson 21 with his responsibilities for Medical. 22 Q Was he the Director of 23 Medical at that time? 24 A A Vice President of 28 1 Medical. 2 Q Anyone else? 3 A No, not at the management 4 level, that would be it. 5 Q The first time that you 6 learned or shortly after you learned about Prozac 7 and fluoxetine hydrochloride, it had not been 8 approved for marketing in the United States, 9 correct? 10 A Yes. 11 Q Would it be characterized 12 that there was a great deal of optimism and 13 excitement concerning the potential of the drug? 14 A Not universally, 15 differing points of view about how big it might 16 be, but generally, yes. 17 Q When you say differing 18 points of view about how big it might be, what do 19 you mean by that, sir? 20 A I mean that the 21 scientific community at Lilly had greater 22 enthusiasm and optimism than the marketing folks 23 did, significantly different. 24 Q Is that not unusual over 29 1 your years at Lilly to have optimism on one end 2 and pessimism on the other? 3 A When there is a 4 difference, that's usually the way, but there was 5 a greater difference on this occasion than on some 6 others. 7 Q What is your recollection 8 with respect to why that was? 9 A Just the fact that the 10 scientists had a better understanding at the 11 cellular molecular level, of its virtues and why 12 it should be superior and different to the 13 existing agents already on the market. 14 Q And the marketing 15 individuals, were they pessimistic about the 16 potential market for antidepressants or were they 17 pessimistic about the fact that Prozac wouldn't 18 offer any differences in connection with treatment 19 of depression? 20 A If I used the term 21 pessimistic -- and I don't believe I did -- I 22 misspoke. We're talking about different levels of 23 optimism that ranged from moderately high to 24 extremely high, not between optimism and 30 1 pessimism. 2 Q I appreciate your 3 correcting me, and it wasn't my intention to use 4 the term pessimism if you didn't use it, and 5 that's why I gave you those cautionary 6 instructions earlier, Doctor Perelman, about 7 correcting me, and feel free to correct yourself 8 if you think you misspoke, and I appreciate you 9 doing that, all right? 10 So we can be accurate, 11 initially could it be said that marketing was less 12 optimistic than the scientific arena? 13 A Yes, sir. 14 Q Did you consider yourself 15 as part of the scientific arena at that time? 16 A No. 17 Q Where did you place 18 yourself? 19 A Well, first of all, a 20 member of senior management, and also a -- with my 21 international responsibility, more related to the 22 marketing, manufacturing and marketing folks, but 23 having the advantage of enough of scientific 24 background and close linkages to have a better 31 1 appreciation for the science side than my fellow 2 management and marketing colleagues. 3 Q When was it that you felt 4 like you had moved from the scientific side of the 5 corporation into the management side? 6 A When I moved from the 7 scientific side to the management side? 8 Q Yes. 9 A When I moved from England 10 back to the United States in 1970. 11 Q As a scientist with a 12 Ph.D. in chemistry, did you do anything to 13 investigate or in any way validate the claims made 14 by the scientists at Eli Lilly that Prozac would 15 have good potential as an efficacious 16 antidepressant? 17 A Only by way of luncheon 18 conversation or coffee break conversation with old 19 friends from the Research Labs, and I would 20 characterize that as just pursuing my interest for 21 a better understanding of the substance, not a 22 matter of attempting -- I would have no need to 23 validate or investigate, I would have complete 24 faith in their judgment skills. 32 1 Q Who were the individuals 2 at that time who were bringing you up to date on 3 that and were giving you a little further 4 scientific insight into the product? 5 A Oh, over the period of a 6 few years, it would have been a whole host of 7 folks that I happened to sit down with at lunch or 8 at a coffee break, and I couldn't possibly 9 reconstruct the cast of characters, but numerous 10 folks over a long period of time. 11 Q Would that have included 12 Doctor Leigh Thompson? 13 A Yes. 14 Q Would that have included 15 Doctor Robert Zerbe? 16 A Yes. 17 Q Doctor Herr? 18 A Yes. 19 Q Anyone else within the 20 CNS area that you had discussions concerning this 21 product with? 22 A Oh, I can clearly recall 23 more than once chatting with Ray Fuller. 24 Q But as far as you were 33 1 concerned then, and I would assume throughout the 2 course of the product, you were looking to 3 individuals such as Doctor Thompson, Zerbe and 4 Fuller to be specifically responsible for the 5 scientific issues presented by the product? 6 A Yes, sir. 7 Q Did you in any way or at 8 any time have to give approval from the management 9 standpoint for the marketing of Prozac? 10 A Yes. 11 Q Tell me when that was and 12 in what capacity you gave approval, sir. 13 A Well, I would have been a 14 member of the Product Strategy Committee when it 15 was presented comprehensively before the 16 submission of the New Drug Application, and again 17 prior to its first marketing after approval some 18 years later. I would also have been present as a 19 member of the Board at the Board of Directors 20 meeting where it also would have been reviewed for 21 safety and efficacy prior to the New Drug 22 Application submission in this country and prior 23 to first marketing overseas and first marketing in 24 this country. 34 1 Q All right, so the 2 approval process that you were involved in was in 3 your capacity as a member of the Product Strategy 4 Committee and as a member of the Board of 5 Directors of Eli Lilly and Company? 6 A That's correct. 7 Q I was wondering whether, 8 since you were the President of Lilly Research 9 Labs in 1987 when the FDA gave their approval for 10 the marketing of that product in the United 11 States, would you have had to certify in your 12 corporate capacity as the President of Lilly 13 Research Labs that Lilly was willing to market the 14 product? 15 A Only in the sense that I 16 would have prevented it in going forward to the 17 Product Strategy Committee and certainly the Board 18 if I had any doubts or concerns, but there was not 19 any formal certification or sign-off, if you will. 20 Q All right, by you? 21 A By me. 22 Q Would there have had to 23 have been a formal certification or sign-off by 24 some officer of the corporation before it could 35 1 have been marketed anywhere? 2 A To my recollection and 3 knowledge, the Product Strategy Committee approval 4 and the Board approval constituted the necessary 5 sign-offs. 6 Q Did I understand you to 7 say, Doctor Perelman, that in your capacity that 8 you had the ability to prevent the marketing of 9 Prozac had you been of the opinion that Prozac was 10 not safe or efficacious? 11 A Not unilaterally, no. I 12 believe I indicated that I could inhibit -- I 13 think was the expression I used -- in going forth 14 to PSC. If I had done so, it will have led to, 15 I'm sure, senior management discussions as to what 16 the problems were and we would have a group 17 discussion and arrive at some conclusion. 18 Q Were there to be a 19 conflict within that group discussion of senior 20 management concerning whether or not to market 21 Prozac, who would have been the individual that 22 would have had responsibility to resolve that 23 conflict? 24 A Well, in the sense such 36 1 an occurrence has never happened during my career, 2 I can't speak from experience nor are there 3 written procedures, but one would assume in the 4 end the Chairman of the Board is where the buck 5 stops. 6 Q Mr. Wood? 7 A Mr. Wood. 8 Q But you felt as a member 9 of senior management a responsibility yourself for 10 the safety and efficacy of this product? 11 A Oh, certainly. 12 Q Do you know of any other 13 members of the senior management of Eli Lilly and 14 Company, other than yourself and Mr. Wood, who 15 would have had similar feelings with respect to 16 having responsibility for the safety and efficacy 17 of the product? 18 A Well, I would 19 characterize all of my colleagues and senior 20 management as feeling that as incumbent upon them 21 for the reputation of the company and ethics and 22 so forth. But more formally, of course, I 23 reported at that time, as President of the 24 Research Labs, to Doctor Herr, who also had 37 1 responsibility for manufacturing as well as the 2 Lilly Research Laboratories, and definitionally or 3 on an organizational basis he would certainly have 4 direct line responsibility and commitment in the 5 same way. 6 Q Was Doctor Herr a medical 7 doctor? 8 A No, he's a biochemist. 9 Q Did you have discussions 10 with Doctor Herr, since you and he are both 11 chemists, concerning Prozac and its qualities? 12 A Yes. 13 Q Tell me about those 14 discussions. 15 A There's nothing really 16 specifically I can say. We lunched together, our 17 offices were yards apart, and we met on an ad hoc 18 basis frequently, many times per day sometimes, 19 sometimes once every couple of days, and when a 20 product is getting near to submission of the New 21 Drug Application or approval of the New Drug 22 Application, it's very topical and the sort of 23 thing you might discuss repeatedly. Beyond that, 24 I can't speak specifically. 38 1 Q You don't have any 2 recollection of any specific conversations where 3 you all were talking about serotonin specific 4 reuptake inhibitors or anything of that nature 5 from a scientific standpoint? 6 A No, I can't be that 7 specific. 8 Q Did you independently 9 have any understanding in connection with the 10 properties of fluoxetine to inhibit the reuptake 11 of serotonin? 12 A Did I independently, did 13 you include the word independently? 14 Q Yes, sir. 15 A Only in the sense that as 16 the compound showed promise and was moving through 17 clinical trials, and I had these sorts of informal 18 discussions with a number of people, some of whom 19 we've enumerated, I began to learn of that in our 20 discussions, Ray Fuller and others, but that's 21 outside of my area of training and knowledge. I 22 don't even think receptors were known when I was a 23 student. 24 Q Even at Rice University? 39 1 A Even at Rice. So that 2 was on-the-job training just by discussions 3 amongst colleagues. 4 Q By virtue of your 5 on-the-job training and discussions with 6 colleagues, and by virtue that you were trained as 7 a chemist, did you become convinced that 8 fluoxetine hydrochloride did possess qualities 9 that would cause a physiological change in human 10 brains? 11 A I was convinced -- yes, 12 is the proper answer; yes. 13 Q And did you, by virtue of 14 your training and experience and discussions with 15 other scientists at Eli Lilly and Company, become 16 of the opinion that fluoxetine hydrochloride could 17 affect mood in some humans? 18 A Yes. 19 Q Are you of the opinion, 20 sir, that depression can, in individuals, some 21 individuals, be caused by a physiological 22 abnormality or status in human beings? 23 A Yes. 24 Q Then were you of the 40 1 opinion that Prozac could, in some individuals, 2 affect that abnormality or status in humans? 3 A Yes. 4 Q And thus cause changes in 5 mood? 6 A Yes. 7 Q When was it, Doctor 8 Perelman, that you first became aware that there 9 was any individual or group or agency or entity 10 that was concerned with respect to whether or not 11 Prozac could be linked to suicidal or aggressive 12 violent behavior? 13 A I believe, and I can't be 14 totally accurate on this, but I believe it was at 15 the time of the Teicher publication. If there 16 were events predating that, I do not recall any of 17 them. 18 Q Give me a second, I want 19 to pick out something that may help your 20 recollection. 21 A All right. 22 (PERELMAN EXHIBIT NO. 1 MARKED FOR 23 IDENTIFICATION.) 24 Q (BY MR. SMITH) Doctor 41 1 Perelman, I'm going to hand you what's been marked 2 as Perelman Exhibit 1 and ask you to review that 3 for a minute, please, sir. 4 A All right, sir. 5 Q Do you recognize Exhibit 6 1? 7 A Yes. 8 Q That appears to be 9 minutes of the Pharmaceutical Product Strategy 10 Committee, correct? 11 A Yes. 12 Q Dated August 1, 1984? 13 A Correct. 14 Q And is that the Product 15 Strategy Committee that you were referring to 16 earlier? 17 A Yes, sir. 18 Q And I assume that there 19 was someone present at those meetings to take 20 notes with respect to what had occurred during the 21 meetings? 22 A Yes. 23 Q And then it was their 24 duty to later transcribe what had occurred during 42 1 the meetings? 2 A Yes. 3 Q And the first page of 4 Exhibit 1 apparently dates the minutes and 5 identifies who was present at the meeting, 6 correct? 7 A Yes. 8 Q And it identifies you as 9 being present at that particular meeting? 10 A That's correct. 11 Q Did you make it a 12 practice to try to attend all of the 13 Pharmaceutical Product Strategy Committee meetings 14 in 1984 that you could? 15 A I did. 16 Q And were you a regular 17 member of that committee? 18 A Yes, sir. 19 Q I see Doctor Herr's name 20 as a member present there. 21 A Yes. 22 Q Of the other individuals 23 that were there that day, were there any others 24 who were senior in management to you? 43 1 A Senior to me -- 2 Q At the time. 3 A At that time. 4 Q And I assume you told me 5 Doctor Herr was senior to you at that time? 6 A Yes. 7 Q Or at least you reported 8 to him? 9 A That's correct. Well, 10 Doctor Pettinga would have been senior to me as an 11 executive vice president, and Mr. Step, I'm not 12 sure when he became executive vice president. We 13 were either lateral or he was more senior at that 14 time. I'm a bit uncertain as to -- I think at 15 that time he was not yet an executive VP nor was 16 Doctor Herr. Oh, I'm sorry, I misspoke, at this 17 time I was President of International and would 18 not have been reporting to Doctor Herr; this 19 is '84 as opposed to '86, so at this time I was 20 reporting to Mr. Wood. 21 Q Were you a member of the 22 Board of Directors of Eli Lilly and Company at 23 that time? 24 A I believe it was 1976 44 1 that I went on the Board, so, yes. 2 Q Page 2 of that document, 3 even though it's marked Page 5, and I'll explain 4 that, these are documents that have come from your 5 file, however, the Court has only required Lilly 6 to produce those documents relevant to Prozac or 7 fluoxetine hydrochloride, and I'm not trying to 8 trick you, that's just the only document 9 apparently that was produced for that meeting in 10 connection with Prozac. 11 A If I may, as a minute 12 point of clarification for myself, it looks like 13 this may have come actually from Mr. Step's file 14 since it shows the marking that would usually be 15 made, but regardless, I would have had a copy 16 myself almost certainly. 17 Q It was your practice to 18 maintain copies of the Strategy Committee meeting 19 minutes, was it not? 20 A Not invariably. I would 21 retain some, maybe the majority, but not every 22 single one. 23 Q The last paragraph of 24 Page 2, which is marked as Page 5 of Exhibit 1 -- 45 1 A Yes. 2 Q -- indicates, quote, the 3 BGA has requested additional data to complete the 4 German submission on fluoxetine. 5 A Uh-huh. 6 Q Additional data are to be 7 supplied to the BGA by October. Do you see that? 8 A Yes. 9 Q Do you recall any 10 discussion at that time, Doctor Perelman, in 11 connection with what data it was that the BGA was 12 requesting? 13 A I recall, aided by this 14 generally, discussions on the questions that were 15 being raised by them, and I would not have known 16 it was at this meeting, but seeing these minutes, 17 it's obviously one place that it was. 18 Q That's why we wanted to 19 give that to you. 20 A Right. 21 Q What was the discussion 22 in connection with the issue or the data that the 23 BGA wanted? 24 A After this period of 46 1 time, of course, my recollection is fuzzy. There 2 were a fair number of questions I recall. I 3 recall questions related to safety as it related 4 to phospholipidosis, a side effect in animals, and 5 I believe there was on the efficacy side in 6 Europe, we used a similar study design as in the 7 US and it turns out the psychiatric practice in 8 Europe would have preferred some -- and the 9 authorities would have preferred a different 10 protocol and measurements, so there were some 11 efficacy issues related to that at that time, as I 12 recall. 13 Q Do you recall that 14 efficacy issue as being that the German government 15 wanted some in-hospital, inpatient studies done? 16 A I recall that was a 17 European issue. As to which countries in Europe, 18 I no longer can recall. It was more than one 19 country in Europe that wanted studies, more of 20 that type, yes. I can't be specific if Germany 21 was one of them. 22 Q Do you recall whether or 23 not the BGA at that time was concerned about 24 Prozac as having a potential for suicide or 47 1 aggressive behavior? 2 A No, I can't recall that. 3 Q And you don't remember 4 any discussion in connection with that issue? 5 A No. 6 (PERELMAN EXHIBIT NO. 2 MARKED FOR 7 IDENTIFICATION.) 8 Q (BY MR. SMITH) Doctor 9 Perelman, Exhibit 2 is minutes of another meeting 10 of the Pharmaceutical Product Strategy Committee, 11 correct? 12 A Yes. 13 Q Some eight months later 14 than the August '84 meeting? 15 A That's correct. 16 Q It's dated April 3, 1985? 17 A Yes. 18 Q And at that time the 19 minutes reflect that there was some discussions in 20 connection with Germany and approval in Germany, 21 correct? 22 A Uh-huh. 23 Q The minutes at that time 24 indicate, "Germany: Study design, i.e. 48 1 classification of depression, suicide potential, 2 and overall lack of German and/or European studies 3 were the main issue raised by the BGA. Lilly 4 responses are aimed at avoiding a rejection of the 5 application. As an alternative, consideration 6 will be given to withdrawal of the application and 7 resubmit it once all the issues have been 8 resolved, particularly if these require the 9 completion of local German studies," correct? 10 A Yes. 11 Q Now, that document 12 reflects that suicide potential was being raised 13 at least by the German government, correct? 14 A Yes. 15 Q Do you, sir, have 16 recollection of a discussion of suicide potential 17 in connection with fluoxetine, Prozac, at that 18 time? 19 A And related to Germany or 20 any other registration? 21 Q Yes. 22 A No, I do not. 23 Q Specifically you don't 24 have any recollection of Prozac and suicide 49 1 potential being raised by Germany? 2 A That's correct. 3 Q And generally you don't 4 recall it being raised by any entity at that time? 5 A Any regulatory entity at 6 that time, that's correct. 7 Q In April of 1985? 8 A That's correct. 9 Q Obviously there are 10 minutes that reflect that there was some 11 discussion of suicide potential at that time, 12 correct? 13 A Correct. 14 Q Do I understand it being 15 your testimony that today, as we sit here, you 16 don't recall that discussion? 17 A That's correct. 18 Q You're not saying that 19 the minutes are inaccurate -- 20 A Oh, no. 21 Q -- and that discussion 22 didn't occur? 23 A No, absolutely not. 24 Q Do you recall who it will 50 1 have been that would have presented this problem 2 or this issue of suicide potential as being raised 3 by the German government? 4 A No, I can't. I can 5 conjecture but that's, I don't think, appropriate. 6 Q By looking at those 7 individuals listed on Page 1 of Exhibit 2, who 8 would have been the individual that you would have 9 assumed would be responsible for making that kind 10 of presentation to the committee? 11 A If I may divert for a 12 moment. 13 Q Sure. 14 A As I look up at the top 15 of the page, it indicates T.L. Emmick, Tom Emmick 16 updated the committee, et cetera, specifically 17 addressing the issues involved with the following 18 countries. So if the minutes accurately reflect 19 what transpired, it would seem that Doctor Emmick, 20 but I'm only parroting what I'm reading, not from 21 any knowledge or recollection. 22 Q Who is Doctor T.L. 23 Emmick? 24 A Currently Doctor Emmick 51 1 is a Vice President of Lilly Research Laboratories 2 responsible for the development area. At this 3 time, under Doctor Herr, he had responsibility in 4 the medical area. I don't recall whether he was 5 an executive director or a vice president at that 6 time. 7 Q Was Doctor Emmick a 8 medical doctor? 9 A No. 10 Q What was his area of 11 specialty? 12 A As it happens, organic 13 chemistry. 14 Q How many organic chemists 15 did you have at that time at Lilly? 16 A Oh, a few hundred. 17 Q It makes sense since 18 you're making a chemical product. 19 A Yes, sir. 20 Q Doctor Perelman, if you 21 had had some scientific concern with respect to 22 suicide potential and Prozac, would you have 23 required some kind of investigation at that time? 24 A At this time? 52 1 Q Yes. 2 A Well, again, I must 3 stipulate that I was President of International, 4 but as a Board member, officer of the company and 5 member of senior management, I certainly would 6 have spoken up, yes. 7 Q Does it cause you concern 8 now that you see that Germany back in 1985 was 9 raising the question of Prozac and suicide 10 potential? 11 A No, sir. 12 Q Does it surprise you -- 13 A No, sir. 14 Q -- that this was raised 15 at this date by the German government? 16 A In a general sense I 17 respond no, because with product after product, 18 one or another or a few regulatory agencies raise 19 a whole host of issues to which we then respond as 20 part of general practice and usually satisfying 21 their interest, concerns or questions. So, this 22 is not exceptional. 23 Q But if Prozac presented a 24 potential for suicide, that would be something 53 1 that would be of great concern to you as a member 2 of senior management? 3 A Yes. 4 Q And if you held the 5 scientific opinion that Prozac did have a 6 potential for causing suicidality, would you have 7 stopped the approval process? 8 A I don't know that I 9 unilaterally had the power to stop it, but again 10 as a member of senior management, I would have 11 felt it incumbent upon me to weigh in with my 12 views and pursue them, yes. 13 (PERELMAN EXHIBIT NO. 3 MARKED FOR 14 IDENTIFICATION.) 15 Q (BY MR. SMITH) Exhibit 3 16 is a -- was it a telex or E-mail or something of 17 that nature? 18 A It looks like an E-mail, 19 yes. 20 Q Dated June 26, 1984? 21 A Yes, sir. 22 Q It appears that it's from 23 your German affiliate? 24 A Yes. 54 1 Q Directed to Indianapolis? 2 A Yes. 3 Q At that time you were the 4 president of Eli Lilly International, were you 5 not? 6 A That's correct. 7 Q And would activities of 8 German registration of Prozac have been your 9 responsibility? 10 A It's more the 11 responsibility of the medical component of the 12 Lilly Research Laboratories, but without 13 abdication by line management of International as 14 well. 15 Q You were on the Board of 16 Directors -- 17 A Yes. 18 Q -- of Eli Lilly and 19 Company at that time, were you not? 20 A That's correct. 21 Q And those directors would 22 have looked to you, as would Mr. Wood have looked 23 to you, as responsible for securing approval of 24 their products in foreign countries by virtue of 55 1 you being President of Eli Lilly International, 2 would they not? 3 A What I was attempting to 4 say is that is not strictly the case. They would 5 have been looking to the Lilly Research 6 Laboratories with their global responsibility for 7 overseeing clinical trials and getting 8 registrations perhaps more so than line management 9 of International; whether sixty/forty or 10 seventy/thirty, it was a bit more of the LRL 11 bailiwick than International. It was a shared 12 responsibility. 13 Q Then would it be accurate 14 to say this was a responsibility that you would 15 have shared in your capacity at the time? 16 A That's correct. 17 Q And then once you became 18 president of Lilly Research Laboratories, that 19 would have certainly been in your area, would it 20 not? 21 A That's correct. 22 Q Now, had you ever seen 23 this document before today, Doctor Perelman? 24 A You see that I was not a 56 1 carbon copy or primary addressee, but whether 2 someone might have shared a copy with me, it's 3 possible. I certainly don't recall it. 4 Q But today, as far as you 5 can presently recall, is the first time you've 6 seen this document? 7 A That's correct. 8 Q And if you turn to Item 9 10 on this document, it indicates that comparative 10 use of concomitantly taken hypnotics and 11 benzodiazepines in agitated/retarded fluoxetine 12 patients versus agitated/retarded patients on 13 comparators. Reason: The BGA suspects fluoxetine 14 to be a stimulating/activating drug, paren, 15 side-effect profile, suicides, suicide attempts, 16 close paren, period, correct? 17 A That's what it read, yes. 18 Q Now, this is dated June 19 1984, correct? 20 A Yes. 21 Q And the minutes of the 22 Pharmaceutical Product Strategy Committee is April 23 3, 1985 where the discussion of suicide potential 24 is brought up, correct? 57 1 A Uh-huh. 2 Q Is that a yes? 3 A Yes. 4 Q Was it explained at that 5 time or is there any relationship with respect to 6 the concerns of the German government raised by 7 this telex to the concerns mentioned in the 8 minutes of the Product Strategy Committee meeting? 9 A That would be 10 conjecture. I can't sit here now and say yes or 11 no. 12 Q You just don't recall one 13 way or the other? 14 A No, sir. 15 Q And I believe you've 16 already testified that you certainly don't have 17 any recollection that there was a problem in 1984 18 in connection with the use of Prozac and a 19 side-effect profile of suicides and suicide 20 attempts? 21 A That's correct. 22 Q Would this have been 23 something that you would have wanted to know as 24 Director of International at the time, or 58 1 President of Eli Lilly International? 2 A It's something that I 3 would have wanted to know and it's also something 4 which I am virtually certain I would have been 5 advised of, I simply am not able to recall it. 6 Q Do you know why this is 7 something that you wouldn't recall, especially in 8 light of the serious issues that have been raised 9 by these lawsuits and in the press? 10 A Well, aided by these 11 documents that you've shared with me, I now recall 12 that there were regulatory questions in this time 13 frame that predate Teicher, but specifically what 14 country or any details, I cannot specifically 15 recall. 16 Q Okay, so could it be said 17 that in 1990, when you became aware of the Teicher 18 article and the potential link of Prozac and 19 suicide, that you at that time recall -- well, 20 this was an issue that was raised by some 21 regulatory authorities at sometime earlier? 22 A Now again aided by seeing 23 these documents to refresh my memory -- 24 MR. FREEMAN: The 59 1 question is did you recall it when you read the 2 Teicher article, not today. 3 A Oh, I'm sorry, thank you 4 for that correct. I can't say with certainty. 5 Q Well, was there any 6 discussion in discussions that you had with other 7 members of Lilly management in 1990 when you 8 learned of the Teicher article that this had been 9 a problem or had been an issue that had been 10 raised by foreign regulatory bodies previous to 11 Teicher raising it? 12 A I cannot specifically say 13 that that's the case, that I recall that. 14 Q I'm trying to bring your 15 memory back to 1990, where it will have been 16 fresher, and I can understand why you might not 17 have recalled the specific problems back in 1984, 18 but you say now I recall that there was some 19 problem or that there was some issue at the time. 20 I'm just wondering in 1990, did anybody bring it 21 to your attention, well, doctor Teicher raised 22 this and this was something that had been raised 23 earlier by regulatory bodies? 24 A And I can only respond 60 1 again that I cannot specifically clearly recall 2 that that sort of discussion took place. 3 Q All right. I assume then 4 you don't have any knowledge concerning what might 5 have been done back in 1984 in connection with 6 this issue that was raised by the German 7 government? 8 A Only a general knowledge, 9 recollection that we, of course, seriously 10 addressed the questions and undertook activities 11 which obviously later led to registration in 12 Germany. 13 Q Well, let me see if I 14 understand, Doctor Perelman, because as I 15 understand it, it's your testimony that when this 16 issue of suicide was raised by Doctor Teicher, you 17 didn't even remember that it had been raised 18 earlier -- 19 A That's correct. 20 Q -- by some regulatory 21 authority? 22 A That's correct. 23 Q Then how do you recall 24 that there had been problems solved when this 61 1 issue came up by regulatory authorities in the 2 past? 3 A I didn't say this issue. 4 My point is that I recall that questions were 5 raised by the German authorities. I referenced 6 earlier what some of those were that I recall. 7 The fact that we subsequently did get approval in 8 Germany, that we did take action to respond to the 9 questions or we would not have gotten approval, 10 that doesn't, I don't believe, contradict the fact 11 that I did not, do not specifically recall the 12 suicide issue being one of those in Germany, or 13 the specifics of how we may have addressed that 14 specific issue, that specific question. 15 Q All right. 16 A Was my answer clear for 17 you? 18 Q I think that helps. 19 Well, do you recall that the application for 20 registration in Germany was withdrawn by Lilly? 21 A Yes. 22 Q And do you recall the 23 reason for that? 24 A It certainly helps to 62 1 have read the minutes of the PSC. It was 2 preferable to withdraw it and respond to the 3 questions and resubmit rather than have it denied 4 and then have to resubmit again. 5 Q Why would that have been 6 preferable? 7 A It's the nature of the 8 German bureaucratic system in the BGA that it 9 takes longer to -- it goes to the bottom of the 10 stack and you start all over again and it takes a 11 longer period of time to get reassessment of your 12 New Drug Application if it has been rejected, so 13 it was just a pragmatic approach as to the most 14 expeditious way to respond to the BGA. 15 Q In all candor also, 16 Doctor Perelman, it looks better if you don't have 17 a flat out rejection, doesn't it? 18 A That's your assessment, 19 not mine. 20 Q Would my assessment be 21 unreasonable? 22 A It may vary by country; I 23 don't know specifically in Germany, don't know the 24 system that closely to know. 63 1 Q From a corporate 2 perspective at Eli Lilly and Company, wouldn't it 3 make sense that it would look better to withdraw 4 an application and then later resubmit it? 5 A That sounds reasonable. 6 Q Than to have an 7 application actually rejected? 8 A That seems reasonable, 9 yes. 10 (PERELMAN EXHIBIT NO. 4 MARKED FOR 11 IDENTIFICATION.) 12 Q (BY MR. SMITH) While 13 your attorneys are looking at Exhibit 4, would the 14 telex that has been introduced as Exhibit 3 that 15 raises this issue of possible suicide have been 16 something that should have been filed with the 17 United States Food and Drug Administration in your 18 opinion? 19 A I'm not an expert on 20 regulatory law, but with that stipulation, it's my 21 judgment that it would not be required to be 22 filed. 23 Q Turn to Point 14 on Page 24 3 of that exhibit. That point says, "As we 64 1 already explained by our telex to Doctor Zerbe of 2 June 8, 1984, we need a careful analysis of 3 suicides and suicide attempts: Patient by 4 patient, symptomatology/severity upon entry into 5 the study and week by week until the event 6 occurred, dose of fluoxetine, side effects, et 7 cetera. This is a very serious issue in the 8 opinion of the BGA. It might well be that we will 9 have to recommend concomitant tranquilizer intake 10 for the first two or three weeks in the package 11 literature," is that's correct? 12 A That's what it says. 13 Q I assume you don't have 14 any recollection of the fact that Ms. Schenk and 15 Doctor Weber were raising this issue at that time? 16 A No. 17 Q By virtue of the fact 18 that this indicates that suicide might be a very 19 serious issue in the opinion of the BGA, would you 20 think that this would be something that the FDA 21 should have received? 22 A No. 23 Q Why is that, sir? 24 A Not prior to our pursuit 65 1 of the question being raised and seeing whether 2 there is merit and validity to it. To my 3 knowledge, there is no requirement that when 4 another regulatory agency raises a question that 5 it is required or incumbent upon us to immediately 6 share that with FDA. 7 Q All right. Is it -- I'm 8 sorry, were you complete in your answer? I didn't 9 mean to cut you off. 10 A Yes. 11 Q Is it your position here, 12 Doctor Perelman, that unless Lilly has satisfied 13 itself in connection with an issue presented for 14 safety by a foreign regulatory board that this in 15 fact does present a safety issue, that it doesn't 16 have to be submitted to the Food and Drug 17 Administration? 18 A There is not a simple yes 19 or no answer to that, it depends on the 20 circumstances. If it's a quite unexpected, 21 unrelated occurrence, or if it's an occurrence 22 that is suddenly occurring at much greater 23 frequently so again as to be unexpected, we would 24 normally notify FDA. Where suicides, suicidality 66 1 is a well known, if you will, side effect, 2 regrettable occurrence in depressed people, in 3 depressed patients, and was being observed, the 4 answer in this circumstance, in my judgment, and 5 I'm not medical qualified, is that it was not 6 necessary or appropriate to proceed to the FDA at 7 this stage. 8 Q But this Exhibit 3, this 9 telex is raising suicide not as a side effect of 10 depression, but is raising the issue with respect 11 to whether or not it's a side effect of Prozac, 12 isn't it? 13 A We are faced -- yes is 14 the first answer, but we are faced with many 15 questions raised by many regulatory agencies as 16 they pursue their business, and just because a 17 question is raised does not require, in my 18 judgment, immediate reporting to FDA. 19 Q All right. Now, at this 20 time, Doctor Perelman, Prozac had not been 21 approved by the Food and Drug Administration, had 22 it? 23 A That's correct. 24 Q In fact, Prozac, with 67 1 respect to whether it was a safe product, was 2 still under investigation by the Food and Drug 3 Administration, wasn't it? 4 A That's correct. 5 Q Would you not feel, as a 6 member of the Board of directors at Eli Lilly and 7 Company, Doctor Perelman, that the Food and Drug 8 Administration in the United States of America 9 should have knowledge concerning the fact that the 10 German government was raising the question with 11 respect to whether or not this product might be 12 causing a clear safety risk, i.e. suicides? 13 A I would not. 14 Q Doctor Perelman, have you 15 ever seen Exhibit 4 before? 16 A I don't recall ever 17 seeing it, no. 18 Q That is a document dated 19 April 1985, is it not? 20 A Yes. 21 Q In the same month of 22 Exhibit 2, which is the April 3, 1985 23 Pharmaceutical Product Strategy Committee meeting 24 minutes where there is mention of suicide 68 1 potential in Germany, correct? 2 A Yes. 3 Q And that document 4 indicates that there was a meeting that occurred 5 in Germany, correct? 6 A That's correct. 7 Q And at that time you 8 would have been the President of Eli Lilly 9 International, in April of '85, correct? 10 A Yes. 11 Q But you were physically 12 located in Indianapolis, Indiana? 13 A That's correct, yes. 14 Q The document indicates 15 that this is a fluoxetine or Prozac Working 16 Session, does it not? 17 A It does. 18 Q And that the objective of 19 the meeting was to make Professor -- and if you'll 20 turn to the last page, it indicates that his name 21 is probably Herrmann? 22 A Yes. 23 Q To make Professor 24 Herrmann and his coworker familiar with fluoxetine 69 1 data so that he is in a better position to give 2 best advice as a consultant to the company in the 3 registration process of fluoxetine, correct? 4 A Yes. 5 Q In Germany, right? 6 A Yes. 7 Q Now, do you know any 8 Professor Herrmann in Germany? 9 A No, I do not. 10 Q Never heard of Doctor 11 Herrmann or Professor Herrmann? I don't know if 12 he's a doctor or not. 13 A Well, I may have at the 14 time; I don't recollect it now. 15 Q It indicates that 16 Professor Herrmann or the group at least reviewed 17 the original documentation submitted March 1, 18 1984, does it not? 19 A It does. 20 Q Do you have any idea what 21 they are talking about when they say original 22 documentation submitted March 1, '84? 23 A Only conjecture. 24 Q What would be your 70 1 opinion in connection with respect to what that 2 means? 3 A I assume that that was 4 the New Drug Application put together for the 5 German affiliate to submit. 6 Q Item 2 of data that was 7 reviewed was an analysis of pooled studies 8 fluoxetine versus imipramine versus placebo, 9 Protocol 27, submitted October 26, '84, correct? 10 A Yes. 11 Q Now, deposition testimony 12 up to date, Doctor Perelman, has indicated that 13 Protocol 27 was a specific protocol that was 14 submitted and done and it's a multi-center study 15 comparing Prozac, imipramine and placebo, all 16 right? 17 A All right. 18 Q Have you ever seen 19 Protocol No. 27? 20 A No. 21 Q Do you have any idea what 22 its contents are? 23 A Not prior to reading 24 this. 71 1 Q All right. The document 2 indicates that Professor Herrmann, or we assume 3 it's Professor Herrmann, left a twenty-one-page 4 opinion, does it not? 5 A It does. 6 Q Then Exhibit 4 indicates 7 that the essential points are summarized as 8 follows, doesn't it? 9 A Yes. 10 Q Have you ever seen any 11 twenty-one-page opinion authored by any expert in 12 Germany hired by Lilly as a consultant in the 13 registration of Prozac in Germany? 14 A No, sir. 15 Q Do you think this would 16 be something that you would remember had you seen 17 it? 18 A Possibly. 19 Q Specifically by virtue of 20 what's said on the second page, do you think you 21 would have remembered it? 22 A Possibly, yes. 23 Q The second page of this 24 exhibit has a section on safety -- 72 1 A Yes. 2 Q -- that was apparently 3 authored by Doctor Herrmann, correct, or the 4 consultant, whoever he was? 5 A Apparently, the way the 6 memo reads. 7 Q And this is apparently, 8 the way the memo reads, a summary of what that 9 opinion was, isn't it? 10 A Yes. 11 Q In connection with 12 safety? 13 A Yes. 14 Q Look down with me to the 15 seventh bullet point under Safety. 16 A Yes. 17 Q Still not resolved is the 18 fact that suicide attempts have been observed more 19 frequently on fluoxetine as compared to 20 imipramine, paren, only epidemiologic data or 21 literature on other antidepressants may help to 22 identifying whether it happened by chance that 23 incidence of suicide attempts was abnormally high 24 on fluoxetine or abnormally low under comparators, 73 1 close paren, period, correct? 2 A Yes. 3 Q Had you ever heard, 4 Doctor Perelman, that there was a consultant at 5 Lilly that had observed more frequently suicide 6 attempts on Prozac as compared to imipramine? 7 A I don't recall that 8 specifically to be the case. 9 Q Do you recall it to be 10 generally the case? 11 A No. 12 Q Do you recall this is the 13 issue that was presented in the Product Strategy 14 Committee meeting in April '85 where they talk 15 with in Germany there being a suicide potential 16 question being raised? 17 A I'm sorry, what was your 18 question? 19 Q Do you recall that this 20 issue of the fact that a consultant had found 21 apparently that suicide attempts were observed 22 more frequently on Prozac as compared to 23 imipramine as being the problem that Germany was 24 raising in connection with suicide potential in 74 1 this April '85 meeting? 2 A No, I cannot tie those 3 two together. 4 Q You can't correlate the 5 two together? 6 A That's correct. 7 Q The document indicates 8 under the next bullet point, "Except nausea, 9 fluoxetine's side effect spectrum is unequivocally 10 more favorable than that of imipramine, but 11 according to today's knowledge this is negatively 12 affected by the increased suicidal risk," correct? 13 A That's the way it reads. 14 Q Is this the first time 15 you've heard of that, Doctor Perelman? 16 A I cannot say yes, that's 17 the first time; I can only say that I do not 18 recall that. 19 Q Would the fact that Lilly 20 had an expert in April of 1985 that was raising a 21 question that was talking about increased suicidal 22 risks with Prozac negatively affecting the side- 23 effect profile of Prozac, would this be something 24 that you feel should have been submitted to the 75 1 United States Food and Drug Administration? 2 A Not without further 3 investigation. 4 Q I guess my question is, 5 apparently the consultant in Germany, by virtue of 6 the fact that he's written a twenty-one-page 7 report, has pretty well investigated this and 8 identified it as a problem, has he not? 9 A That's the way this 10 reads, yes. 11 Q But you don't have any 12 recollection of anybody at Lilly presenting this 13 report to you or this problem to you? 14 A No. 15 Q Would this have been 16 something you would have wanted to know as the 17 President of Eli Lilly International at the time, 18 Doctor Perelman? 19 A Yes, and it's probable I 20 did, I was made aware of it. 21 Q Then do you have any 22 explanation as to why you don't recall it being 23 raised to you at the time if it was probable that 24 it was raised? 76 1 A The only logical 2 explanation is a faulty memory. 3 Q Well, you've not been 4 criticized for a faulty memory before, have you, 5 Doctor? 6 A Yes. 7 Q By anybody at Eli Lilly? 8 A Yes. 9 Q Who has criticized you 10 for a faulty memory at Eli Lilly? 11 A In facetious, semi 12 facetious manner, several people, I can't quote 13 you who or when or an instance. 14 Q Have you ever been 15 concerned about the quality of your memory up to 16 this date, Doctor Perelman? 17 A Candidly, yes. 18 Q When did you first begin 19 to have some concern about your memory? 20 A Years ago. 21 Q Has that always been a 22 concern for you? 23 A Yes, sir. 24 Q Have you felt that you 77 1 needed to seek medical attention for that problem? 2 A Nothing that severely. 3 Q Apparently the 4 consultant, in his report, had a benefit/risk 5 ratio because at the bottom of Page 2 it indicates 6 benefit/risk ratio, correct? 7 A Let's see, bottom of Page 8 2? 9 Q Actually it's marked 3. 10 A Okay, C is labeled 11 benefit/risk ratio, right. 12 Q And it says the 13 benefit/risk ratio was not unequivocally positive, 14 doesn't it? 15 A That's what it says. 16 Q It says therefore it is 17 of great importance to determine a certain type of 18 patients who will better respond to fluoxetine 19 than to imipramine so that higher risk might be 20 acceptable, is that correct? 21 A That's the way it reads. 22 Q Had you ever heard of any 23 attempt to determine certain types of patients who 24 would respond better to Prozac than to imipramine? 78 1 A I have, but not related 2 to an issue of higher benefit to risk ratio. 3 Q In what connection have 4 you heard that recommendation? 5 A It has always been -- let 6 me back up for a moment. It is a medical fact I 7 am told that all of the antidepressants of 8 whatever type, whatever mechanism, are only 9 effective in two-thirds or seventy percent of the 10 patients, and it's a bit of hit or miss as to 11 which works and which doesn't in any given 12 patient. It obviously would be a great marketing 13 and medical advantage if one could find a marker, 14 an identifier that would say this is a patient who 15 would greatly benefit from this antidepressant, 16 that or the other, so in that sense it was being 17 exhibited. 18 Q All right, then what you 19 are telling me is that there has always been an 20 effort by Lilly to define people who would be most 21 likely to be optimally benefited by Prozac? 22 A The only way I would 23 qualify that is I believe earlier your reference 24 about my awareness of discussions. 79 1 Q Yes, sir. 2 A I'm not aware that we 3 ever found anything that caused us to implement a 4 study of that type. In other words, we're probing 5 for concepts or ideas to identifying a population, 6 such a population who would singularly benefit 7 from Prozac, but we never carried out a study of 8 that type or implemented because we were not able 9 to come up with the concept, with the possible 10 solution. 11 Q Was there any effort on 12 the other side of the coin by anybody at Lilly to 13 probe or find individuals who would potentially 14 have damaging reactions to Prozac? 15 A Yes. 16 Q What was done in that 17 connection? 18 A Discussions again were 19 carried out, and certainly after the -- again 20 referring to the Teicher publication, as to 21 whether there was any way to identifying a subset 22 of the population who might be more inclined to 23 suicide or suicidality. 24 Q All right. But there was 80 1 nothing of that sort done before the Teicher 2 article, by Lilly? 3 A No. Not to my 4 recollection, I should add. 5 Q Do you know why this 6 document would have Page 2 at the top and Page 3 7 at the bottom where we've been reading, Doctor 8 Perelman? 9 A I certainly don't. I 10 didn't even notice it until you called it to my 11 attention. 12 Q I didn't either until I 13 was trying to refer you to a page and saw that it 14 had two different pages? 15 A I would suggest that 16 since the top of the next page says 3, the 3 at 17 the bottom of this page is erroneous and the 2 at 18 the top is probably correct. 19 Q The last page of this 20 exhibit indicates that the probability of getting 21 Prozac approved in Germany is low, doesn't it? 22 A Yes. 23 Q Because of the 24 benefit/risk ratio discussed above, correct? 81 1 A Yes. 2 Q And that benefit/risk 3 ratio was a situation where there was going to be 4 a need to find a group of individuals or group -- 5 a certain type of patients who would better 6 respond to Prozac than imipramine? 7 A Yes. 8 Q The document goes on to 9 say that in order to have a successful outcome 10 there might have to be a limited indication, that 11 is a use of the product in mild to moderate 12 endogenous depression plus precautionary statement 13 concerning suicidal risk, correct? 14 A Yes. 15 Q Had you heard at that 16 time or had you heard up until 1990 that the 17 German government was considering a precautionary 18 statement concerning suicidal risk? 19 A I recall that there was a 20 period of time in which it was being suggested 21 that in order to get approval we might have to 22 require -- that we might be required to have more 23 limited indications and maybe some other 24 cautionary statements, but beyond that, no 82 1 specifics. 2 MR. FREEMAN: Is this a 3 good time for a break? 4 MR. SMITH: Okay. 5 (SHORT BREAK TAKEN.) 6 Q (BY MR. SMITH) Do you 7 recall, Doctor Perelman, that Prozac was approved 8 for sales in Germany? 9 A Yes. 10 Q And do you recall that 11 the brand name of Prozac in Germany was Fluctin, 12 or is Fluctin, I assume it still is? 13 A Yes. 14 Q Did you know that there 15 is a package insert that identifies Fluctin, 16 Prozac, in connection with the risk of suicide? 17 A No, I don't specifically 18 know that that's the case in Germany. 19 Q Well, do you know 20 generally that there is a warning and 21 contraindication in the German package of 22 information in connection with Prozac and suicide? 23 A No, in Germany, I do not. 24 Q Do you know whether or 83 1 not there are any other limitations in any other 2 countries pointing toward Prozac and risk of 3 suicide, specifically with respect to their 4 package literature? 5 A No. 6 Q Does that surprise you? 7 A That I do not know it? 8 Q That it is being listed 9 as having a risk of suicide in other countries, 10 specifically Germany? 11 A Given the -- with all 12 products, the variations and requirements imposed 13 by local regulatory agencies, I'm accustomed to 14 variations, so for that reason it wouldn't be all 15 that surprising to me. 16 Q Do you not think it's 17 significant that the German regulatory authorities 18 are requiring that in order for Prozac to be sold 19 in Germany that it have a package insert 20 describing a risk of suicide in connection with 21 Prozac? 22 A No. 23 Q Is it your judgment that 24 this is just a different regulatory body requiring 84 1 different technical warnings? 2 A Yes, something to which 3 we're accustomed. 4 Q Obviously you're not 5 taking the position here, Doctor Perelman, and 6 it's not your testimony that individuals in 7 Germany present any different risk of suicide than 8 individuals in the United States, is it? 9 A Highly improbable. 10 Q Would you have any 11 objection to individuals in the United States 12 being advised that Prozac presents a risk of 13 suicide? 14 A Yes. 15 Q Why is that, sir? 16 A Because we do not feel 17 that that is the case and that would also appear 18 to be the way the FDA feels. 19 Q I'm not talking about the 20 FDA, I'm talking about you as formerly the 21 President of Lilly Research Labs and a long time 22 member of the Board of Directors of Eli Lilly and 23 Company. 24 A My answer nonetheless 85 1 remains the same. 2 Q Do you know of any harm 3 that would come to individuals within the United 4 States were there to be a warning concerning a 5 risk of suicide in individuals, some individuals 6 using Prozac? 7 A Any harm -- 8 MR. FREEMAN: Other than 9 misleading them? 10 Q That would come to 11 individuals in the United States? 12 A Yes, if we do not 13 consider it to be a correct statement, that there 14 is not such a connection, it would be misleading. 15 Q You wouldn't want to have 16 anything in prescribing information in the United 17 States that would be in any way misleading? 18 A That's correct. 19 Q Obviously the prescribing 20 information in the package inserts are primarily 21 directed to physicians, are they not? 22 A That's correct. 23 Q In other words, the 24 public can't go out and buy Prozac without a 86 1 doctor writing a prescription for Prozac, correct? 2 A That's correct. 3 Q And so when I talk about 4 a package insert or a warning, I'm talking about 5 recommendations to physicians. 6 A However, with the 7 stipulation that in some countries, and I'm quite 8 certain that Germany is one of them, there was 9 also a patient package insert, PPI. 10 Q All right. Well, there 11 is a package insert that comes with Prozac in the 12 United States also, is there not? 13 A Yes. 14 Q That can be seen by the 15 patient? 16 A I'm really not certain 17 that there is a PPI in the United States. If you 18 tell me there is, I'll accept that, but of my own 19 knowledge, I don't recall that there is one. 20 (PERELMAN EXHIBIT NO. 5 MARKED FOR 21 IDENTIFICATION.) 22 Q (BY MR. SMITH) Doctor 23 Perelman, I'll hand you what's been marked as 24 Exhibit 5, and I'll represent to you that that is 87 1 a translation of the German package insert, and I 2 would like for you to turn to the third page of 3 that exhibit, which is marked on the top as Page 4 2, and look at that for me, would you? 5 A Yes, sir. 6 Q Under that there is a 7 heading Risk Patients, is there not? 8 A There is. 9 Q And the language there 10 specifically states risk of suicide, colon, 11 Fluctin -- which is Prozac in Germany? 12 A Uh-huh. 13 Q Continuing, Fluctin does 14 not have a general sedative effect on the central 15 nervous system. Therefore, for his or her own 16 safety, the patient must be sufficiently observed 17 until the antidepressive effect of Fluctin sets 18 in. Taking an additional sedative may be 19 necessary. This also applies in cases of extreme 20 sleep disturbances or excitability, correct? 21 A That's the way it reads, 22 yes. 23 Q Now, that is the German 24 package insert, that's the language of the German 88 1 package insert. 2 A All right. 3 Q Would you have any 4 problem with patients in the United States or 5 physicians in the United States receiving this 6 information? 7 MR. FREEMAN: That's two 8 questions in one. Let's first deal with doctors. 9 Q Okay, would you have any 10 problems with doctors in the United States 11 receiving this information? 12 A I would if in the 13 judgment of our medical specialists and the FDA it 14 was not appropriate emphasis to have it in there. 15 Q I'm talking about you, 16 Doctor Perelman, as a member of the Board of 17 Directors and President of Lilly Research Labs. 18 A Well, I in turn need to 19 rely on the judgment of the individuals within 20 Lilly Research Laboratories who have expertise in 21 this area and be guided by their inputs and 22 judgment on that. 23 Q Well, do you, as you sit 24 here, as a chemist, as one familiar with chemistry 89 1 and one who has been on the Board of Directors of 2 a major pharmaceutical firm for a number of years, 3 have any objection to this language? 4 A If those individuals and 5 employees of Lilly Research Laboratories who have 6 the proper qualifications and training to assess 7 the data accumulated in extensive clinical trials 8 indicate to me that in their judgment that this is 9 not an appropriate or necessary warning and can be 10 misleading or incorrect emphasis or focus, yes, I 11 do. 12 Q Who would you look to 13 then in the scientific community at Lilly to pose 14 that question to? 15 A Our clinical experts in 16 the Medical Division. 17 Q I need names. 18 A You need names? 19 Q Yes. 20 A Well, at this time it 21 included Doctor Leigh Thompson, and it would have 22 included the psychiatrists employed at that time 23 to the best of my recollection involving John 24 Heiligenstein and -- let's see, Gary Tollefson is 90 1 on the Board now but I believe would not have been 2 employed at this time, he was leading the 3 psychiatric group. David Wheadon, and I always 4 have trouble recalling the third gentleman with 5 the beard, a very excellent psychiatrist -- 6 Q Doctor Beasley? 7 A Charles Beasley, thank 8 you. 9 Q You say he's an excellent 10 psychiatrist? 11 A Yes, they all are. 12 Q Did you know that Doctor 13 Beasley has never practiced psychiatry outside of 14 his training? 15 A That in no way reduces 16 the very high esteem in which I hold him, as do 17 others. 18 Q Okay. Anybody else that 19 you would look to? 20 A That's the psychiatric 21 expertise that I would turn to, plus Leigh 22 Thompson and Bob Zerbe at that time as well, 23 although he is not a psychiatrist, nor is Leigh 24 Thompson. 91 1 Q Would you have any 2 knowledge concerning whether or not Fluctin does 3 not have a general sedative effect on the central 4 nervous system? 5 A Would I personally? 6 Q Yes. 7 A No. 8 Q Doctor Beasley testified 9 yesterday that Fluctin does not have a general 10 sedative effect on the central nervous system. 11 A He testified to that? 12 Q Yes. 13 A Yesterday? 14 Q Correct. 15 A That's pretty good for 16 me. 17 Q So if he doesn't disagree 18 with that statement, you don't disagree with that 19 statement? 20 A No, sir. 21 Q You don't, of course, 22 have a problem with a patient being sufficiently 23 observed in connection with any Lilly medication, 24 do you? 92 1 A No, sir. 2 Q You don't have to check 3 with a psychiatrist to know that that's good 4 information for a physician in connection with a 5 patient? 6 A That's correct. 7 Q Are you aware of the 8 benefits that might be achieved in connection with 9 Prozac if it's prescribed in conjunction with an 10 additional sedative? 11 A Am I aware of the 12 potential benefits? 13 Q Yes. 14 A No, sir. 15 Q Has anybody made you 16 aware as a member of the Board of Directors of Eli 17 Lilly and Company or as President of Lilly 18 Research Labs, whether or not it may be beneficial 19 to prescribe a sedative with Prozac? 20 A I recall that the issue 21 was mentioned; I don't recall the details of the 22 ensuing discussion. Of course, we did not have, 23 to my recollection, any clinical trials to support 24 such a combination therapy. 93 1 Q Well, you have a 2 psychiatric advisory board to advise the 3 scientists at Eli Lilly and Company concerning 4 psychiatric matters, don't you? 5 A Yes, sir. 6 (PERELMAN EXHIBIT NO. 6 MARKED FOR 7 IDENTIFICATION.) 8 Q (BY MR. SMITH) Exhibit 6 9 is a document that is a Lilly document that was 10 written by an individual by the name of Tina 11 directed to Atul C. Pande -- or Pande Atul, which 12 is it? 13 A Atul Pande. 14 Q You know Doctor Pande, do 15 you not? 16 A He came on board, was 17 hired, I believe, in '93; I know of him, but not 18 well. 19 Q You know he works on 20 Prozac? 21 A Yes. 22 Q You know he is 23 responsible for clinical trials in connection with 24 Prozac? 94 1 A Yes. 2 Q Exhibit 6 is a list of 3 all the clinical trials that use psychoactive 4 medications, is it not, or appears to be? 5 A It appears to be. 6 Q You recognize the 7 designations HCAC, HCCH and those four-letter 8 initials as being Prozac trials, do you not? 9 A I recognize them as being 10 the type of abbreviation or coding system that we 11 use for clinical trials, yes. 12 Q And I'll represent to 13 you, Doctor Perelman, that these are Prozac 14 clinical trials. 15 A All right. 16 Q It's been established 17 that they are clinical trials. Will you take my 18 word for that? 19 A Yes, sir. 20 Q Did you know that 21 psychoactive medication was being administered to 22 individuals participating in Lilly's clinical 23 trials on Prozac? 24 A Psychoactive? 95 1 Q Yes. 2 A I'm just trying to think 3 beyond chloral hydrate is the reason for pausing. 4 No. 5 Q The reason I used the 6 word psychoactive medications is because that's 7 the term used in this document, isn't it? 8 A Yes, up at the top. 9 Q And under that it lists 10 chloral hydrate does it not? 11 A Yes. 12 Q And that was being 13 allowed to be administered to patients on Prozac 14 clinical trials for sleep, was it not? 15 A Well, I'm not sure that 16 necessarily it was for sleep, it was being allowed 17 to be administered. I don't see anything that 18 indicates it's for sleep. 19 Q I'll represent to you 20 that the clinical medical monitors at Lilly and 21 the clinical investigators have testified that the 22 chloral hydrate that is being mentioned here that 23 was used in the clinical trials was administered 24 primarily for sleep, Doctor Perelman. Do you have 96 1 objection to that? 2 A No, sir. 3 Q Additionally, this 4 document indicates that if a patient complains of 5 agitation, some patients in the clinical trials 6 could receive benzodiazepines, correct? 7 A Yes. 8 Q Do you know 9 benzodiazepine is a sedative tranquilizer 10 substance? 11 A Yes. 12 Q Used to reduce agitation, 13 correct? 14 A Among other things, yes. 15 Q Well, this document 16 indicates that if the patient complains of 17 agitation, that the investigator was allowed to 18 administer benzodiazepines, correct? 19 A Yes, but my point being 20 that librium, Valium and other benzodiazepines are 21 used for purposes other than just agitation and I 22 interpreted your question more broadly than this 23 specific instance. 24 Q In this specific exhibit 97 1 it specifically mentions agitation, doesn't it? 2 A Yes, sir. 3 Q There's also some other 4 medications there mentioned, flurazepam, 5 triazolam, temazepam. Do you recognize those 6 medications as a chemist? 7 A I recognize them. I 8 couldn't stake my reputation on the fact that 9 they're all benzodiazepines. They may be. The 10 flurazepam certainly is, and the other two 11 probably are. 12 Q The document indicates 13 that they're at least psychoactive medications? 14 A That it does. 15 Q And the document 16 indicates that they were administered during the 17 clinical trials to patients receiving Prozac in 18 the clinical trials, does it not? 19 A It does. 20 Q And you didn't know that 21 this was occurring during the clinical trials? 22 A I may have been at the 23 time. I'm not -- even aided by this, it 24 doesn't -- I don't recall that that was the case. 98 1 Q Well, you don't dispute 2 that that was the case, do you? 3 A No. 4 Q So patients in the Prozac 5 Lilly clinical trials were receiving sedatives 6 like is mentioned in this German package insert, 7 weren't they? 8 A Yes, on an allowed or 9 as-needed basis, it would appear, not as part of 10 the protocol design. 11 Q Well, the protocols allow 12 the administration of these medications. 13 A That I believe is what I 14 said, it was allowed, it wasn't part of the 15 protocol design that they should be concomitantly 16 administered. 17 Q Well, neither does the 18 German package insert indicate that in all 19 patients everybody should have sedatives, does it? 20 A That's correct. 21 Q So the similarity is that 22 some patients on the clinical trials are getting 23 what some patients in Germany are being 24 recommended, correct? 99 1 A That would appear to be 2 the case, yes. 3 Q Now, you have a 4 psychiatric advisory board at Eli Lilly and 5 Company, do you not? 6 A As I said before, yes. 7 Q And those are 8 psychiatrists thought to be well respected in the 9 field? 10 A Yes. 11 Q Psychiatrists I assume in 12 whom Lilly places some stock in their judgment? 13 A Yes. 14 Q Otherwise you wouldn't 15 have them on your advisory board? 16 A Correct. 17 Q I assume that you have 18 other physicians in other specialties that advise 19 Lilly in connection with other disciplines of 20 medicine? 21 A That's correct. 22 Q For instance, if you've 23 got an antibiotic, you may have an immunologist as 24 an advisory member? 100 1 A Or at least an infectious 2 disease expert. 3 Q Or infectious disease, 4 correct? 5 A (WITNESS MOVES HEAD UP 6 AND DOWN.) 7 (PERELMAN EXHIBIT NO. 7 MARKED FOR 8 IDENTIFICATION.) 9 A Do you wish me to read 10 this in its entirety? 11 Q No. Do you recognize the 12 name of Doctor Jan Fawcett, MD? 13 A Yes. 14 Q Do you recognize him to 15 be a member of the Eli Lilly Psychiatric Advisory 16 Board? 17 A Yes. 18 Q Do you recognize the 19 Journal of Clinical Psychiatry as being an 20 authoritative journal in connection with matters 21 of depression and suicide in mental disorders? 22 A Not necessarily 23 depression and suicide, I recognize it as a very 24 reputable journal in psychiatry. 101 1 Q And you certainly 2 recognize Doctor Fawcett as a reputable physician 3 in the field? 4 A Yes. 5 Q Turn with me to Page 42 6 of the article. 7 A All right. 8 Q Under the general heading 9 Treatment, do you see that? 10 A Yes. 11 Q And under the specific 12 heading Combination Therapy? 13 A Uh-huh. 14 Q The third sentence under 15 combination therapy of Doctor Fawcett's article 16 states, "Few of the antidepressants, especially 17 newer medications, have an early affect on anxiety 18 which may explain the low compliance rate common 19 to this whole therapeutic class. Aggressive 20 treatment with a benzodiazepine anxiolytic is 21 indicated for immediate relief of anxiety in 22 patients with major depression if they manifest 23 risk factors of suicide. If the anxiety is severe 24 or if the antidepressant selected causes 102 1 jitteriness (fluoxetine) or was without sedative 2 properties (desipramine, imipramine and 3 bupropion)." Do you see that? 4 A Yes. 5 Q Did I read that 6 accurately, Doctor, even though I may have 7 mispronounced some of the words? 8 A You did it pretty well. 9 Q There in fact Doctor 10 Fawcett is mentioning his experience that in some 11 patients Prozac may cause jitteriness, isn't he? 12 A Yes. 13 Q And is recommended that 14 in those patients taking Prozac that are jittery 15 that aggressive treatment with a benzodiazepine is 16 indicated, is he not? 17 A Yes. 18 Q The same thing that the 19 German package insert is inferring, isn't it, 20 Doctor Perelman? 21 A I need to look exactly 22 how they worded it. It would appear to be the 23 case, yes, based on this. 24 Q So the German package 103 1 insert is recommending no more and the same for 2 some patients on Prozac that a member of Lilly's 3 own Psychiatric Advisory Panel is recommending, 4 correct? 5 A I think in looking at the 6 two of them, one aspect that suggests itself to me 7 is the labeling risk of suicide in the case of the 8 German label as opposed to reference to 9 jitteriness, anxiety, and there is an implied 10 direct association to me when I read in the German 11 package insert as compared to reading it in the 12 article, which I think could be an important 13 difference. 14 Q Well, is there a 15 difference, Doctor Perelman? If you'll look at 16 the article -- and I don't want to take advantage 17 of you because I know that you haven't read the 18 article in its entirety and I don't want to be 19 accused of taking anything out of context, so stop 20 me if you feel I'm doing that -- but if you look 21 at the article by Doctor Fawcett, he talks on the 22 first page about assessing risk of suicide in the 23 depressed patient, does he not? That's the 24 heading. 104 1 A Okay. 2 Q In bold type, correct? 3 A (WITNESS MOVES HEAD UP 4 AND DOWN.) 5 Q Then under that he's 6 talking about treatment, is he not? 7 A Yes. 8 Q And then he talks about 9 concomitant therapy or combination therapy? 10 A Uh-huh. 11 Q And the first word there 12 is he's talking about suicide prevention is the 13 first line -- is first consideration in treatment 14 of major depression with anxiety, does it not? 15 A Yes. 16 Q And he's talking about 17 aggressive treatment with a benzodiazepine 18 anxiolytic is indicated for immediate relief of 19 anxiety with major depression if they manifest 20 risk factors of suicide, correct? 21 A Yes. 22 Q So in all fairness, 23 Doctor Fawcett is talking about a risk factor of 24 suicide in patients taking antidepressants? 105 1 A Yes. 2 Q And so is the German 3 package insert? 4 A Yes. Taken in the full 5 context, I would agree with your earlier question. 6 Q All right. Do you know 7 Doctor David Dunner? 8 A I know of him. 9 Q All right, do you know 10 that Doctor Dunner was a clinical investigator 11 hired by Lilly to perform clinical trials on 12 Prozac? 13 A Yes. 14 Q Did you know that Doctor 15 David Dunner is a member of Lilly's Psychiatric 16 Advisory Committee? 17 A Yes. 18 (PERELMAN EXHIBIT NO. 8 MARKED FOR 19 IDENTIFICATION.) 20 Q (BY MR. SMITH) Doctor 21 Perelman, I'll represent to you that this is 22 portions of the deposition taken of Doctor David 23 Dunner in this litigation. 24 A Uh-huh. 106 1 Q And Mr. Myers was there 2 at the time Doctor Dunner presented himself for 3 deposition. 4 A All right. 5 Q You're certainly free to 6 read all the material that we've copied here, and 7 I want to represent to you that his deposition was 8 probably two or three hundred pages long, and so 9 I'm going to be reading to you selected pages from 10 that deposition. 11 Would you turn to what's 12 marked as Page 86 in this portion of the 13 deposition testimony and read with me beginning on 14 Line 7 of Page 86, the question there is, "What 15 percentage of your patients would you say have 16 been successfully treated with fluoxetine?" 17 His answer was, "That's a 18 hard question to answer. Because somebody gets 19 better during treatment doesn't mean it's the 20 treatment that got them better. But probably 21 eighty percent of the people I treat get better." 22 The question then was, 23 "Out of the eighty percent, how many of those 24 people percentage-wise have you had to administer 107 1 concomitant sedatives to?" 2 And his answer was, 3 "Including antidepressants?" 4 Then the question was, 5 "Sure," and he says, "Perhaps a third to a half," 6 correct? 7 A Uh-huh. 8 Q Is that a yes? 9 A Yes. 10 Q So it would appear from 11 reading this that Doctor Dunner, one of your 12 clinical investigators and a member of your 13 Psychiatric Advisory Committee, is administering 14 sedatives with Prozac, correct? 15 A That's the way it reads, 16 yes, sir. 17 Q And that that figure 18 could be at least a third to half of his patients 19 receiving Prozac are getting sedatives or other 20 antidepressants with sedatives properties, 21 correct? 22 A Yes. 23 Q Did you know that? 24 A No, sir. 108 1 Q That's what is 2 recommended by the German package insert for some 3 patients taking Prozac, correct? 4 A Yes. 5 Q That's what was done in 6 the clinical trials on Prozac, correct? 7 A Some of the trials 8 apparently, yes. 9 Q And that's what is 10 recommended by Doctor Fawcett, correct? 11 A Yes. 12 Q And that is what is in 13 fact being done by Doctor David Dunner, a 14 psychiatrist in Seattle who was a clinical 15 investigator on Prozac, correct? 16 A Yes. 17 Q Turn with me to Page 223, 18 Doctor Perelman. Line 13, a question by 19 Ms. Zettler, "Is it possible that fluoxetine can 20 cause suicidal ideations?" What's his answer 21 there? 22 A In what cases is it 23 possible -- it says yes. 24 Q Then the question was, 109 1 "In what cases is it possible?" And his answer 2 was, "I don't know." 3 A I don't know. 4 Q Then the next question 5 is, "Is it possible that fluoxetine can cause 6 violent and aggressive behavior?" There was an 7 objection, and then Doctor Dunner answered, "Yes," 8 correct? 9 A Yes. 10 Q Did you know that Doctor 11 Dunner had expressed that it was possible that 12 fluoxetine, Prozac, can cause suicidal ideation? 13 A No, I didn't know that. 14 Q Did you know that Doctor 15 Dunner has testified that it is possible that 16 fluoxetine, Prozac, can cause violent and 17 aggressive behavior? 18 A No. I would like to add 19 to the answer however, not knowing what was in 20 Doctor Dunner's mind, anything is possible. It's 21 impossible to prove an absolute negative, and 22 without getting into his mind or being present to 23 ask questions myself, I am not disturbed by those 24 answers. As a scientist, if you had asked me is 110 1 it possible, with more elaboration, I probably 2 would have said yes as well. 3 Q Well, again, I told you, 4 Doctor Perelman, that this was only a portion of 5 his deposition testimony and that Lilly attorneys 6 were there and Doctor Dunner had his attorney 7 there. 8 A Uh-huh. 9 Q And it certainly says 10 what it says, doesn't it? 11 A Yes, it does. 12 Q And he says it's possible 13 on these pages that I read, does he not? 14 A He does. 15 Q You've never seen this 16 German package insert, have you? 17 A No, sir. 18 Q So you've never reviewed 19 this with the Lilly scientists to know whether 20 they would have any objection to it or not, have 21 you? 22 A No, not in that sense. 23 It would have been discussed at a policy level, 24 without having the package insert before us, you 111 1 know, reviewing it line by line, differentiating 2 between the question and trying to rephrase my 3 answer a little bit. 4 Q But you don't have any 5 specific recollection of this specific inclusion 6 in the German package insert? 7 A No, but -- I'm sorry, I 8 should let you finish. 9 Q If there had been an 10 objection by Lilly, would this have been brought 11 before the Product Strategy Committee or the Board 12 of Directors? 13 A Not the Board of 14 Directors. It's highly likely that it would come 15 before the Product Strategy Committee. 16 Q Do you have a 17 recollection of that occurring? 18 A Not an accurate or 19 precise one, no. 20 Q Do you have a 21 recollection of discussing whether this should be 22 opposed by the committee in discussion with the 23 scientists at Lilly? 24 A I do now recall it being 112 1 discussed, and I assume in a Product Strategy 2 Committee. 3 Q Tell me about that 4 discussion then, Doctor Perelman. 5 A I just recall it was felt 6 to be unwarranted or unmerited, but it was 7 something that we had to do to meet the German 8 authorities and it was agreed reluctantly to do 9 so. 10 Q Well, the decision was we 11 either agree to it or we don't get to sell it in 12 Germany, correct? 13 A Absolutely, that's why we 14 agreed to it. 15 Q Did you know that 16 Mr. Richard Wood has given his deposition in this 17 case where he's testified he doesn't have any 18 objection with this language? 19 A No, I wasn't aware of 20 that. 21 Q You've been the President 22 of Lilly International and the President of Lilly 23 Research Labs, do you have any explanation as to 24 why the German government would require this 113 1 particular warning in this particular product, in 2 this particular way, and the United States Food 3 and Drug Administration would not? 4 A Our experience is replete 5 with instances where regulatory agencies end up 6 with different views and different requirements. 7 Q How do you know who is 8 right or wrong in that situation, Doctor Perelman? 9 A First of all, we have to 10 meet the regulations and laws of the country in 11 which we're being hosted, and it's as 12 straightforward and simple as that. 13 Q So you don't make a 14 determination with respect to who is right or who 15 is wrong, you just meet the regulations? 16 MR. FREEMAN: There's no 17 determination in this case that the two package 18 inserts don't say about the same thing. They're 19 treating a disease, the outcome of which is 20 suicide. 21 MR. SMITH: Mr. Freeman, 22 you weren't present in the conversation where 23 Judge Goddish cautioned counsel -- 24 MR. FREEMAN: That is an 114 1 objection and you are mischaracterizing what the 2 two package inserts say. 3 MR. SMITH: -- about 4 coaching the witness. 5 MR. FREEMAN: You're 6 mischaracterizing it completely. 7 MR. SMITH: We object to 8 your side bar remark and your coaching the 9 witness. 10 MR. FREEMAN: It's not 11 coaching the witness, it's a fact. You are 12 misleading the witness. 13 MR. SMITH: Would you 14 read my question back? 15 REPORTER: (READING) So 16 you don't make a determination with respect to who 17 is right or who is wrong, you just meet the 18 regulations? 19 A No, that's not correct. 20 Q What is correct in that 21 aspect then? 22 A After meeting the 23 requirements of each individual country, unless we 24 feel that it is totally wrong or incorrect, we 115 1 make a judgment as to the merits of the case and 2 either act or do not act to make that change in 3 other countries as well. 4 Q Okay. The German 5 government has required that you give this 6 particular package insert in connection with 7 Prozac and the risk of suicide, correct? 8 A That's correct. 9 Q And you agreed to do that 10 to market the product in Germany? 11 A That's correct. 12 Q And you did that because 13 in order to market the product in Germany you 14 would have to have a package insert concerning 15 that language? 16 A That is correct. 17 Q My next question then is, 18 is there an analysis made in meeting a particular 19 regulatory requirement of another country, like 20 Germany, as to whether or not that particular 21 regulatory body is right or wrong in requiring 22 that particular warning? 23 A When it is a 24 significant -- as this would be, a significant 116 1 type of change in the package insert literature, 2 such an assessment is made. 3 Q All right. Is this 4 assessment made before or after you agree to 5 market the product in that particular country 6 under that particular warning? 7 A It would depend on how 8 rapidly they approve. Let me -- that may not 9 be -- that may be too vague an answer. Once the 10 German authorities require a certain change and we 11 come to the position that if we're going to market 12 in that country we have to agree to it, then we 13 agree. Now, the assessment would normally be 14 taking place simultaneously as to whether it's of 15 sufficient merit that we ought to notify all other 16 countries, including the United States, that we 17 desire to make an identical or similar change in 18 those countries. Whether it's always before or 19 after or simultaneously, I can't say, and it may 20 vary with the instance. 21 Q Well, the German package 22 insert, I believe the language of the German 23 package insert was inserted by Lilly before the 24 Teicher article came out, all right? 117 1 A I don't know that for a 2 fact. 3 Q Will you accept that? 4 A If it's a fact that 5 you're representing to me, I'll accept it, yes. 6 Q Certainly we know that 7 the concern, by virtue of these exhibits that 8 we've reviewed here, that the concern of the 9 German government was made known to Lilly long 10 before the Teicher article? 11 A Yes. 12 Q And certainly there was 13 an indication that this labeling concerning this 14 warning concerning the risk of suicide might very 15 well be required of Lilly before they could market 16 the product in Germany? 17 A Yes. 18 Q And there was a decision 19 made to withdraw the application in Germany for a 20 while, correct? 21 A Correct. 22 Q But then it was 23 resubmitted? 24 A Yes. 118 1 Q And approved with the 2 requirement that Prozac have this particular 3 warning concerning risk of suicide? 4 MR. FREEMAN: Wait just a 5 minute, and I object to that. The document speaks 6 for itself. It says risk patients, it says 7 dysfunction of liver. Those are the types of 8 patients, risk of suicide, that's the type of 9 patient they're taking about. They're not talking 10 about Fluctin causing these things. We object, 11 you are mischaracterizing because that is simply 12 not what it says. 13 MR. SMITH: The document 14 says what it says. 15 MR. FREEMAN: It says 16 risk patients, you'll agree with that, don't you? 17 It doesn't say risk of Prozac. 18 MR. SMITH: Neither one 19 of us fortunately are under oath or giving our 20 deposition. 21 MR. FREEMAN: Don't 22 mischaracterize the document because it doesn't 23 say what you're saying it says. 24 MR. SMITH: Don't give me 119 1 instructions. The document speaks for itself, 2 Counsel. Don't give me instructions with respect 3 to this deposition. 4 MR. FREEMAN: Don't 5 mischaracterize. 6 MR. SMITH: You either 7 make an objection or instruct your client or your 8 witness not to answer the question. 9 MR. FREEMAN: Go ahead 10 with your questions. 11 Q (BY MR. SMITH) The 12 document speaks for itself concerning risk 13 patients, does it not? 14 A Yes. 15 Q And lists risk of suicide 16 under risk patients, does it not? 17 A Yes. 18 Q Now, when you make the 19 decision to market the product -- I think this is 20 important, so bear with me -- when you make the 21 decision to market the product with this 22 particular language of the German package insert, 23 do you make a decision with respect to whether or 24 not that governmental body is correct or incorrect 120 1 in requiring that you present this particular 2 language under risk patients? 3 A Correct or incorrect. 4 Well, you start out with the premise that it has 5 to be there because they are the law of the land, 6 and unless it is totally erroneous, off base, it 7 is the price we pay to do business in that 8 country. We make an evaluation as to whether we 9 think it has sufficient merit and is in proper 10 balance and perspective that it should also be 11 considered for inclusion in all other countries. 12 I don't know how to answer it more briefly than 13 that or to just say yes or no. 14 Q Are you saying that if 15 you make the decision that the particular package 16 insert, the German package insert has a scientific 17 basis so it would be beneficial to other 18 individuals in other countries, then you'll make 19 application to change or add that to the labeling 20 in the other countries that it's not contained in? 21 A If we conclude in our 22 judgment that it has that merit. 23 MR. SMITH: Do you want 24 to stop and eat now? 121 1 A I think one other thing I 2 would like to add as a postscript to that 3 statement is that I believe it's our procedure 4 that when such a change is required by the German 5 authorities, that we make it known to the FDA, and 6 I point out that if they thought it had 7 substantial merit and would be very beneficial, 8 they would impose -- they certainly have their own 9 free will to impose that upon us. 10 MR. SMITH: Okay. 11 (LUNCH BREAK TAKEN.) 12 Q (BY MR. SMITH) Doctor 13 Perelman, before we broke for lunch we were 14 talking about what Lilly would do in connection 15 with requirements of various regulatory agents 16 with respect to labels, correct? 17 A That's correct. 18 Q In that connection, is 19 there a procedure in place at Lilly where if a 20 label change is suggested by a regulatory body or 21 if you are going to market the product initially 22 in a particular country and they require a 23 labeling that is different from other countries, 24 is there a procedure in place at Lilly to review 122 1 existing labeling to make a determination with 2 respect to whether or not there should be any 3 changes or additions or deletions by virtue of the 4 decision of a particular regulatory body that 5 would alter an existing label? That's a long 6 question and I'll be glad to have it read back. 7 A I believe I understand 8 it. There is not a written or formal procedure. 9 However, invariably when such a change is 10 recommended or required of that nature, it would 11 be a routine operating procedure for the medical 12 people to assess it and in their judgment, when 13 it's of any significance, substantial 14 significance, to consult with their marketing 15 colleagues as well, and then if again it's of very 16 broad significant influence and there is a 17 decision to either fight for its -- continue to 18 struggle or change or to accept it and to consider 19 implementing across the board, it would surface 20 for senior management to be made aware of and to 21 have an opportunity to ask questions and challenge 22 or agree. 23 Q And of course senior 24 management would have to make the approval of the 123 1 change? 2 A Yes. 3 Q Senior management would 4 be the ultimate group responsible for any 5 alterations or changes? 6 A Yes, there would be times 7 when it was in the view of the middle management 8 of Marketing and Medical that it was not of such 9 consequence that it did not need to surface there, 10 so it's a judgment call. 11 Q Why would Marketing have 12 an input on this? 13 A Simply because when the 14 product is in the marketplace, they might have 15 questions that they would want to raise that 16 should be considered that the Medical would not be 17 aware of, they might ask questions with regard to 18 competing products in the class, chemical class or 19 therapeutic class and do they have it in and why 20 not. Since they're the ones that are going to 21 sell the product eventually, they certainly ought 22 to have an opportunity to raise questions. 23 Q If it is a labeling 24 change with respect to safety, shouldn't the 124 1 scientific end have the decision making ultimatum 2 in that situation? 3 A Oh, without question, the 4 final decision rests with Science and Medicine, 5 not with Marketing, but we work in a collegial 6 manner and they have an opportunity, as I said, to 7 weigh in. 8 Q Were you aware that 9 Marketing was establishing what they call a wish 10 list in connection with the Plan D clinical 11 studies of Prozac? 12 A I don't know whether -- I 13 don't know of it being labeled a wish list or what 14 this reference to the wish list might specifically 15 refer to, but Marketing does provide to Medical a 16 list of the type of trials they would like to 17 see. I have no idea whether what is being labeled 18 as a wish list corresponds to that. 19 Q I don't think there's any 20 need to take up time, while we've got it 21 highlighted, I'll just point you to that so you'll 22 know I'm not trying to mislead you in connection 23 with that. 24 A All right. 125 1 (TENDERED.) 2 MR. FREEMAN: Take your 3 time and look it over. One is just a copy of the 4 other. 5 A All right. Well, the 6 reproduction quality is poor enough, but I'm 7 pretty sure I've understood it appropriately and 8 sufficiently. 9 Q And based on me handing 10 you this document which was introduced in another 11 deposition, you understand what I'm saying by 12 marketing wanting a wish list in connection with 13 Plan D studies? 14 A Yes. 15 Q Was there a procedure or 16 was there an informal analysis made when the 17 German government made this requirement that you 18 have this language in the German package insert 19 concerning Prozac and the risk of suicide about 20 potentially changing the label in other 21 jurisdictions, specifically the United States? 22 MR. FREEMAN: Objection; 23 that's a misstatement of what the German insert 24 says. 126 1 A Would you then please -- 2 MR. FREEMAN: Read the 3 question. 4 REPORTER: (READING) Was 5 there a procedure or was there an informal 6 analysis made when the German government made this 7 requirement that you have this language in the 8 German package insert concerning Prozac and the 9 risk of suicide about potentially changing the 10 label in other jurisdictions, specifically the 11 United States? 12 A Yes, there would be. I 13 cannot quote chapter and verse on it, but there 14 was discussion about not only the acceptance of it 15 in Germany, but whether one ought to make similar 16 changes in other countries, including the United 17 States. 18 Q Do you remember who would 19 have been involved in those discussions, Doctor 20 Perelman? 21 A No, I do not recall. 22 Q Would those discussions 23 have been made before or after it was decided to 24 acquiesce with respect to the German government's 127 1 requirement in connection with this language in 2 their package insert? 3 A There again, I'm not sure 4 whether before or after or both. 5 Q Can you give me some 6 names of individuals that would have been involved 7 in this discussion? 8 A It would be speculation. 9 Q On a general basis in 10 connection with Prozac and those individuals that 11 you listed earlier, can you give us any help as to 12 who might have been involved in that? 13 A Recognizing that I'm 14 speculating, I just don't -- I simply don't know. 15 Do you want speculation? 16 Q No. It was Lilly's 17 practice from time to time to call in consultants 18 with respect to scientific issues presented by 19 Prozac, was it not? 20 A Yes. 21 Q And it was Lilly's 22 practice to attend and sponsor various conventions 23 of experts in particular areas, correct? 24 A Convention, maybe mini 128 1 symposia? 2 Q Yes. 3 A Yes. 4 Q Meetings where members of 5 the particular specialty were held? 6 A Yes. 7 Q I'm staying in the Omni 8 Hotel and I noticed last night when I came in that 9 there was a Lilly International Convention going 10 on specifically with respect to psychiatrists 11 there. Did you know that? 12 A No. 13 MR. SMITH: Is Hans Weber 14 here, Counsel, for that. 15 MR. MYERS: I don't know 16 who is there. 17 MR. SMITH: Do you know, 18 Mr. Freeman? 19 MR. FREEMAN: I don't 20 know anything about it. I didn't even know there 21 was a conference going on. 22 (PERELMAN EXHIBIT NO. 9 MARKED FOR 23 IDENTIFICATION.) 24 Q (BY MR. SMITH) The 129 1 German package insert speaks of sedatives and 2 speaks of cases of extreme sleep disturbances or 3 excitability, does it not? 4 A Yes. 5 Q The first paragraph of 6 this Exhibit 9, which appears to be a trip report 7 authored by Doctor Leigh Thompson and dated June 8 13, 1988 indicates that Doctor Thompson had been 9 to a Psychiatrist Experience Program and that he 10 is reporting on this trip, is that right? 11 A That appears to be the 12 case, yes. 13 Q And there in the fifth 14 paragraph on the first page he says "Doctor," and 15 then the name of that doctor is blacked out -- 16 A Uh-huh. 17 Q -- "and others noted use 18 of Prozac plus fifty to one hundred milligrams of 19 trazodone to ameliorate the sleep disorder. It 20 works with the first dose," correct? 21 A That's what it reads, 22 uh-huh. 23 Q Were you aware of -- and 24 I know you are not copied here, but were you aware 130 1 of Doctor Thompson's attendance at this 2 Psychiatrist Experience Program where he reported 3 back to Doctor Masica and others that 4 psychiatrists were using Prozac with trazodone? 5 A Actually I am copied on 6 this one, the second name there. 7 Q Okay. 8 A And so I would have read 9 it at the time. 10 Q Do you recall receiving 11 this? 12 A No, I can't say that I 13 specifically recall receiving it. 14 Q Did you make it a 15 practice to read memos such as this where you were 16 carbon copied? 17 A Oh, yes. 18 Q You were meticulous in 19 going through all of your mail that you got and 20 your correspondence within the corporation? 21 A Some might say 22 compulsive. 23 Q Is that right? 24 A (WITNESS MOVES HEAD UP 131 1 AND DOWN.) 2 Q What would you normally 3 have done with something of this nature, a memo 4 such as Perelman 9? 5 A Well, depending on 6 obviously the nature of the content, it would be 7 anything from the trash, to the file, to making a 8 phone call, or stopping by an office if there was 9 something I wanted further information or 10 clarification on. 11 Q What file would this have 12 ended up in or what conduct would you have taken 13 in connection with this? 14 A I cannot speak from 15 knowledge and say that I recall that as a result 16 of this I did any one of the three, and I'd better 17 not conjecture about what I did. 18 Q If it had raised some 19 specific concern in your mind, you would have 20 taken some action, but you think it would be 21 likely that you would recall it at this time? 22 A Probably. 23 Q Were you aware in 1988 24 that, as Doctor Leigh Thompson put it, there was 132 1 tremendous pressure from gurus and practicing 2 psychiatrists to make ten milligrams or even five 3 milligrams available? 4 A I was aware that there 5 were pressures, suggestions, wishes, tremendous 6 pressures, I think it's usual energetic 7 flamboyance, in my estimation, but I can't fix it 8 as to 1988, but sometime certainly back in 9 the '80s and continuing into the early '90s there 10 were wishes for that, yes. 11 Q Do you recall 12 participating in any meetings with the scientific 13 personnel where they were expressing to you as 14 upper management a desire that Prozac be made 15 available at lower dosage? 16 A Yes, upper management was 17 made aware in meetings which I attended of these 18 wishes, yes. 19 Q Did the scientists tell 20 you that there was an opinion by some and concern 21 by others that a higher dosage of Prozac was more 22 likely to cause adverse events? 23 A They indicated that, 24 which was in opposition to our data to the 133 1 contrary. 2 Q Are you telling me that 3 Lilly scientists were telling you something that 4 was contrary to research done by Lilly scientists? 5 A No, no. I'm saying that 6 Lilly physicians, as opposed to scientists, would 7 come back from meetings or from visits to 8 physicians and indicate that some -- and I would 9 characterize it as a relatively small number as 10 opposed to tremendous pressure -- who stated a 11 preference and a desire for a reduced dosage. 12 That's on the one hand, and I'm saying that the 13 in-house medical and scientific views, as it 14 finally came out after many discussions, was that 15 that was not something to be pursued. 16 Q Well, Leigh Thompson was 17 in-house? 18 A Sure, he was in-house, 19 but I said after discussion as it finally worked 20 out. Because one person feels that way, even if 21 that one person is me, it doesn't mean that it 22 automatically happens. 23 Q Well, in fact, Eli Lilly 24 did begin manufacturing Prozac in ten milligram 134 1 form, did they not? 2 A Yes. 3 Q Was that manufacturing 4 process begun before you retired, Doctor Perelman? 5 A Yes. 6 Q Did you have input into 7 that decision? 8 A Yes, although it was -- 9 yes. 10 Q What was your 11 recommendation in connection with respect to 12 whether or not to manufacture Prozac in ten 13 milligram pulvule form? 14 A That as long as we kept 15 the dosage recommendation as before, twenty 16 milligrams, forty, sixty, but primarily twenty, 17 that as a convenience to those members of the 18 medical profession to choose in spite of that to 19 dose downward, or if they wanted to use it in 20 children, as a convenience to the medical 21 community, let's proceed. 22 Q Your understanding that 23 the reason for the manufacture of Prozac in ten 24 milligrams pulvules was to enable it to be used in 135 1 some respects in dose downward fashion? 2 A Yes. 3 Q That is less than twenty 4 milligrams? 5 A That's correct. 6 (PERELMAN EXHIBIT NO. 10 MARKED FOR 7 IDENTIFICATION.) 8 Q (BY MR. SMITH) Exhibit 9 10 is a memo written by Doctor John Heiligenstein, 10 one of your in-house psychiatrists, correct? 11 A Yes. 12 Q One of your scientists at 13 Eli Lilly and Company? 14 A One of our physicians, 15 uh-huh. 16 Q Wouldn't you consider him 17 a scientist? 18 A I think of a scientist as 19 the basic researchers in the laboratory as opposed 20 to a clinician. He's a medical scientist, let's 21 not trip over that. 22 Q I think Doctor 23 Heiligenstein would say he was doing research for 24 Lilly also. 136 1 A As a research clinician, 2 not a scientist. 3 Q But he supposedly or is 4 supposed to use the scientific methods in his work 5 at Lilly, is he not, Doctor Perelman? 6 A Yes. 7 Q This is dated November 7, 8 1990 and concerns a meeting that he attended in 9 Vienna? 10 A Yes. 11 Q Would that be Vienna, 12 Austria? 13 A I would certainly assume 14 so. 15 Q It says that, "Given the 16 angst post-Vienna, I would like to share the sense 17 of what I heard. 1. Clearly, very clear there is 18 a need for a lower dose in pulvule form. Five 19 milligrams would be most appropriate, although at 20 the child psychiatry meetings in Chicago, two 21 point five was suggested. The liquid formulation 22 will only partially address this need. 23 "2. We have not 24 established the lowest effective dose and if we 137 1 listen to the prescribers some effort should be 2 made to do this; if not, MD's will continue to 3 dissolve pulvules and will anxiously await new 4 medications with greater flexibility in dosing," 5 correct? 6 A That's the way it reads. 7 Q So the way I read this, 8 Doctor Perelman, not only was there an opinion 9 from outside physicians that Prozac be 10 manufactured in less than ten milligram form, but 11 it was Doctor Heiligenstein's position that Prozac 12 should be manufactured at a reduced dosage; do you 13 agree with me in that? 14 A I guess you would have to 15 ask Doctor Heiligenstein as to whether he shared 16 that or whether he was reporting what he was 17 hearing and simply responding to it. I can't tell 18 that unambiguously. 19 Q What caused me -- and it 20 is somewhat ambiguous. But what caused me to 21 think that perhaps Doctor Heiligenstein was 22 concerned about this, he said, "If we listen to 23 the prescribers, some effort should be made to do 24 this; if not, MD's will continue to dissolve 138 1 pulvules," et cetera, does that say to you that 2 Doctor Heiligenstein was of the recommendation 3 that it be manufactured at a lower dose? 4 A That's the way it would 5 read, yes. 6 Q Is it true from what you 7 know, Doctor Perelman, that Lilly, in November 8 1990, had not established the lowest effective 9 dose of Prozac? 10 A I cannot give a yes or no 11 to that because we had established a dose response 12 curve which was surprisingly flat, and found that 13 although there was slightly reduced efficacy at 14 ten versus twenty, it was not very great, the 15 slope was fairly flat. And that even at five, we 16 could distinguish antidepressant activity. So 17 there is effectiveness, but is it as effective and 18 to the same degree qualitatively and 19 quantitatively in as large a percent of the 20 population. So, when you say effective, yes, it 21 was definitely effective at five. There was a 22 suggestion, however, that it was not as effective 23 as at twenty. 24 Q Well, maybe the correct 139 1 way to say it would be that Lilly had not 2 established the lowest effective dose, but Lilly 3 had established the most effective dose; do you 4 understand the distinction that I'm drawing? 5 A Yes, and we concluded 6 that twenty milligrams was the most effective 7 dose, and also that when we looked at the 8 incidence of side effects at sixty versus forty 9 versus twenty, that it was the optimum dose in the 10 sense of effectiveness and reduced side effects. 11 Q But when you looked at 12 it, the data established also that there was less 13 side effects on ten milligrams than twenty, wasn't 14 there? 15 A No, sir, I do not recall 16 that. The sample size at ten and at five, as I 17 recall, was not a large enough one to have strong 18 statistical significance to my recollection, and 19 that if we wanted to get that, it would entail 20 much larger and longer studies. 21 Q But you did have 22 statistical information indicating effectiveness 23 of ten and five milligram dosage of Prozac in 24 antidepressant treatment? 140 1 A Effectiveness, period, in 2 that sense, yes. 3 Q Mr. Wood, when he gave 4 his deposition last week, indicated that he felt 5 that the scientific group was over emotional in 6 their insistence or request that Prozac be 7 manufactured at doses lower than twenty 8 milligrams; do you agree with that? 9 MR. FREEMAN: I'm not 10 sure he said it in exactly that way. 11 A Regardless of how he may 12 have said it, if he said it as the scientific 13 group, I think that's very much in error. There 14 were a few individuals to my recollection who 15 would like to have seen the study, but the 16 scientific group or the medical group as taken as 17 a body, to my understanding and recollection, were 18 in favor of doing exactly what we did, in not 19 proceeding with the substantial additional studies 20 that would have been required to get first our own 21 approval and then regulatory approval for a 22 reduced dose. 23 Q But it was approved at a 24 reduced dose? 141 1 A It was approved at a 2 reduced dose -- a reduced dosage presentation, but 3 I don't believe at a reduced dose. In other 4 words, it's presented as here's a ten milligram 5 for those who want it, but if you read the package 6 insert, I believe it still indicates identical to 7 the twenty milligram product, however the wording 8 goes, about most people are satisfactorily treated 9 at twenty milligrams, allow it ten or twenty days 10 for effectiveness, and then move on to forty if 11 you choose, or after treatment therapy even to 12 sixty. I don't believe that it indicates that ten 13 milligrams is the dosage that is recommended. 14 Q No, I'm not indicating 15 that there was a change in recommended dosage. 16 A But that's an important 17 differentiation and I misinterpreted then what you 18 said about the ten milligram dosage. 19 Q I apologize. 20 A It's probably my fault. 21 Q I didn't mean to 22 mischaracterize what you said. In fact, Prozac 23 was manufactured at a dosage of ten milligrams? 24 A Yes. 142 1 Q Which was half the dosage 2 originally manufactured? 3 A Yes, but I just must add 4 again, however, the recommended dosage for usage 5 was not changed. 6 Q I understand that. That 7 was going to be my next -- 8 A I keep restating it 9 because it's very important. 10 Q When it was finally put 11 on the market at ten milligrams, there was no 12 change in the recommended dosage? 13 A That's correct. 14 Q Who was it there at Lilly 15 who was recommending that studies be done to 16 examine whether to reduce the recommended dosage? 17 A After this time and all 18 the discussions, I can't call to mind who the 19 individual, or even individuals plural, may have 20 been. 21 (PERELMAN EXHIBIT NO. 11 MARKED FOR 22 IDENTIFICATION.) 23 Q (BY MR. SMITH) German 24 package inserts recommends sedatives in some 143 1 individuals being treated with Prozac for 2 depression, correct? 3 A Yes. 4 Q Apparently that's not a 5 new idea, is it, when you look at Exhibit 11? 6 A Okay, no. 7 Q Because in July 1984 8 there was a fluoxetine Medical/Marketing staff 9 meeting where the usefulness and future potential 10 of a combination drug, i.e. antidepressant and 11 tranquilizer in unipolar depression was discussed? 12 A Yes. 13 Q In other words, within 14 Lilly back in 1984, there were discussions 15 concerning the usefulness and potential of 16 combining Prozac and tranquilizers? 17 A That would seem to be the 18 case as reflected in these minutes, yes. 19 Q And specifically that's 20 mentioned right at the middle of Page 1, is it 21 not? 22 A Yes. 23 Q I want to switch gears 24 with you a little bit, Doctor Perelman, and 144 1 discuss what arose after the Teicher article came 2 out in February 1990, okay? 3 A Uh-huh. 4 Q That was your first 5 knowledge, even though we've given you a lot of 6 documents that have helped you recall some 7 discussions of Prozac versus suicide, but that was 8 the first time it ever became an issue of United 9 States importance, would that be accurate? 10 A Yes. 11 Q Up to that point, it was 12 a regulatory question in Germany as far as you 13 were concerned? 14 A Yes. 15 Q Earlier, Mr. Wood has 16 advised that Doctor Leigh Thompson had made a 17 presentation to the Board of Directors at Eli 18 Lilly and Company concerning the question of 19 Prozac and suicide; do you recall that, that 20 Doctor Thompson had made such a presentation? 21 A When you say earlier, you 22 mean Mr. Wood's deposition? 23 Q Yes. 24 A Not that it was earlier 145 1 than the Teicher? 2 Q Right, thank you for 3 pointing that out. I didn't mean to imply that at 4 all. 5 A Yes, I do recall that. 6 Q The Board minutes, and I 7 apologize, we don't have them here with us, but 8 the Board minutes indicate that Doctor Thompson's 9 presentation was basically that there was no 10 association between Prozac and depression, that 11 suicide was a part of the illness of depression. 12 Do you recall Doctor Thompson making a 13 presentation like that? 14 A Clearly, yes. 15 Q And that the clinical 16 trials had not shown any association between 17 Prozac and suicidality? 18 A Yes. 19 Q And that the clinical 20 trial data supported the conclusion that there was 21 no relationship between Prozac and suicidality? 22 A Yes. 23 Q Or violent aggressive 24 behavior? 146 1 A Yes. 2 Q Do you recall the 3 question of violent aggressive behavior being 4 addressed by Doctor Thompson at this same Board 5 meeting? 6 A No, I couldn't say that 7 it was at that specific same Board meeting, but at 8 a later time, if not at that meeting. 9 (PERELMAN EXHIBIT NO. 12 MARKED FOR 10 IDENTIFICATION.) 11 Q (BY MR. SMITH) Maybe it 12 will be a little difficult to decipher from this, 13 but apparently the testimony -- we've taken Doctor 14 Heiligenstein's deposition, the author of the bulk 15 of this memo. 16 A Okay. 17 Q And by reading this and 18 taking Doctor Heiligenstein's deposition, 19 apparently Doctor Thompson was going to make a 20 presentation to the Board of Directors and to 21 Mr. Wood, correct, does that appear what you -- 22 A I must admit as to being 23 a bit uncertain as to what the final product of 24 this effort was to be. I noticed reference to 147 1 Mr. Wood, but -- oh, here's proposed presentation 2 to the Board, yes, all right, I agree, I didn't 3 catch that. 4 Q And Doctor Heiligenstein 5 has told us that the Board referred to there is 6 the Board of Directors of Eli Lilly and Company? 7 A Yes. 8 Q Of which you were a 9 member at the time? 10 A Yes. 11 Q And apparently Doctor 12 Thompson had received some data and some numbers 13 from the psychiatrists there within his group, 14 correct? 15 A Yes. 16 Q And Doctor Thompson, in 17 his -- I wrote this down, your term, energetic 18 flamboyance, became a little irritated with them 19 because the numbers were -- the information was 20 not given to him at a time when he wanted them, 21 correct? 22 A Yes. 23 Q Do you remember that 24 Doctor Thompson presented slides or verbatims to 148 1 the Board in connection with this issue of Prozac 2 and suicide? 3 A I couldn't specifically 4 say that, but it would be his general practice, 5 but no, I don't recall he used slides. 6 Q It's my recollection, 7 Doctor Perelman, that the minutes of the Board of 8 Directors meetings on that occasion where Doctor 9 Thompson made that presentation indicate that you 10 were present at that meeting. 11 A Oh, yes. 12 Q And you recall being 13 there at the meeting? 14 A Yes. 15 Q You just don't recall 16 whether he presented any slides or not? 17 A Yes. But as I say, he 18 almost invariably did, so I don't know. 19 Q If you look down at the 20 bottom of Page 1 of this exhibit, apparently 21 Charles Beasley, David Wheadon and Doctor 22 Heiligenstein reviewed the data and the numbers 23 and the verbatims before Doctor Thompson presented 24 them to the Board, correct? 149 1 A Yes. 2 Q But not in time for him 3 to change the slides or the verbatims -- well, 4 it's unclear. 5 A Yes. 6 Q We don't know whether he 7 did or not because we haven't taken Doctor 8 Thompson's deposition. 9 A Okay, and that's why I'm 10 shrugging, which I realize is hard to pick up 11 verbally, I can't unequivocally draw that 12 conclusion. 13 Q At the bottom of Page 1 14 Doctor Heiligenstein writes: "We feel that 15 caution should be exercised in a statement that 16 suicidality and hostile acts in patients taking 17 Prozac reflect the patient's disorder and not a 18 causal relationship to Prozac." 19 A Uh-huh. 20 Q It goes on to say, "Post- 21 marketing reports are increasingly fuzzy and we 22 have assigned yes, reasonably related on several 23 reports." 24 A Uh-huh. 150 1 Q Correct? 2 A Yes. 3 Q Did Doctor Thompson tell 4 you at that Board meeting that the psychiatrists 5 on Lilly's staff had assigned yes, reasonably 6 related to several reports of Prozac and 7 suicidality? 8 A I do not recall that he 9 did, no. 10 Q Do you think that you 11 would have recalled that had he told you that some 12 of the psychiatrists within Lilly, in reviewing 13 these reports, post-marketing reports, were 14 assigning reasonably related to Prozac and 15 suicidality? 16 A I think that it's quite 17 highly likely that I would remember that, yes. 18 Q That would have caused 19 you some concern had you known that? 20 A Yes, sir. 21 Q You've never seen this 22 E-mail, have you? 23 A Not to the best of my 24 knowledge or recollection. 151 1 Q Would this have been 2 something you would have wanted to know at the 3 time? 4 A Yes, unless or again 5 interaction and further study analysis led to a 6 consensus that that was not the case I would add 7 as a further stipulation. 8 Q But it would be important 9 to you as the President of Lilly Research 10 Laboratories at the time and a member of the Board 11 of Directors of Eli Lilly and Company to know that 12 some of Lilly's employees, whose job it was to 13 examine these post-marketing reports and make some 14 determination with respect to whether or not there 15 was a causal relationship between Prozac and 16 suicide, were saying that they were, yes, 17 reasonably related, correct? 18 A Let me repeat myself and 19 clarify better. Yes is the answer unless in the 20 interval between this exchange and Doctor 21 Thompson's presentation to the Board further 22 interaction between Doctor Thompson and the 23 psychiatrists resolved the differences in opinion 24 or views. In other words, if by the time he made 152 1 a presentation to the Board the apparent conflict 2 was resolved, there would be no need for me to be 3 aware of it. 4 Q Yes, but a post-marketing 5 1639 report of adverse event, if there's an 6 assignment of yes, reasonably related on those 7 reports, that can't be changed, can it, Doctor 8 Perelman? 9 A It can't be changed with 10 regard to the fact that that's filed with that 11 judgment made with FDA, but the evaluation can be 12 changed through investigation and discussion 13 in-house. 14 Q All right. What would be 15 the first thing that you would expect to be done 16 by the psychiatrists reviewing the 1639's in 17 connection with making a determination, Doctor 18 Perelman? 19 A That's too far from my 20 area of direct involvement. You would need to ask 21 them what they would do. 22 Q Well, if there was a 23 report submitted by a clinical investigator of an 24 adverse experience involving suicide or violent 153 1 aggressive behavior linking -- questioning whether 2 or not in the investigator's -- questioning a 3 relationship between those acts, wouldn't you 4 expect the psychiatrists at Lilly investigating 5 this to seek the investigator's opinion in 6 connection with whether or not the investigator 7 felt the suicidality was related to the ingestion 8 of Prozac? 9 A Not only seek his 10 opinion, but in some or many cases to ask to go to 11 raw data and information to see whether there was 12 agreement validating his opinion; was it an 13 impression or what were the surrounding facts. 14 Q You would at least 15 expect, as President of Lilly Research 16 Laboratories at the time, that your in-house 17 psychiatrists would ask your investigators what 18 they thought and what their professional opinion 19 was concerning whether or not there was a causal 20 connection, wouldn't you? 21 A I believe I've already 22 agreed do that, but that I've indicated as well 23 that there are times when one investigates beyond 24 investigator's opinion. 154 1 Q I'm not suggesting that 2 the investigation stop at that, I'm suggesting 3 that that be a part of the investigation. 4 A And I've agreed twice. 5 Q All right. I won't make 6 you agree again. 7 A Okay, thank you. 8 Q But you don't have any 9 recollection of Doctor Thompson advising the Board 10 of Directors that prior to this meeting his 11 psychiatrists on staff were reporting yes, 12 reasonably related on some post-marketing reports 13 of suicide and violent aggressive behavior? 14 A I do not. 15 Q Turn with me to the 16 second page. And as I understand it, Doctor 17 Thompson, as part of his presentation, indicated 18 that there wasn't any basis for the assertion 19 between suicidality and violent aggressive 20 behavior based on data from the clinical trial? 21 A Yes, that's correct. 22 Q Under Page 5 Doctor 23 Heiligenstein writes, "Suicidal thinking in 24 clinical trials. You may want to note that trials 155 1 were not intended to address issues of 2 suicidality. Also in Paragraph 2, patients were 3 excluded who were serious suicidal risks." Did I 4 read that correctly? 5 A Yes, sir, uh-huh. 6 Q Did Doctor Thompson 7 advise the Board of Directors that the clinical 8 trials were not intended to address the issue of 9 suicidality? 10 A I believe that he did in 11 the sense that that was not part of the original 12 design, yes. 13 Q And did he advise you or 14 did you already know that individuals who were 15 serious suicidal risks had been excluded from the 16 clinical trial? 17 A I already knew and I 18 believe that was even mentioned at the Board. 19 (SHORT BREAK TAKEN.) 20 (PERELMAN EXHIBIT NO. 13 MARKED FOR 21 IDENTIFICATION.) 22 Q (BY MR. SMITH) Have you 23 had an opportunity to review Exhibit 13? 24 A Yes, I have. 156 1 Q Exhibit 13 appears to be 2 a memo that Doctor Leigh Thompson created after a 3 conversation early one morning with Doctor Paul 4 Leber of the Food and Drug Administration, 5 correct? 6 A Yes. 7 Q Do you know Doctor Paul 8 Leber? 9 A Never met him, I know of 10 his reputation. 11 Q Do you know anybody in 12 the Department of Neuropsychopharmacology at the 13 Food and Drug Administration? 14 A No, I do not. 15 Q The subject of the 16 meeting, the telephone conversation was Prozac and 17 suicide, was it not? 18 A Yes, sir. 19 Q And it followed an 20 article in the Wall Street Journal? 21 A Yes. 22 Q Was it unusual for 23 ranking members of Lilly's medical division to be 24 speaking directly with ranking members of the Food 157 1 and Drug Administration concerning safety issues 2 that were in the public eye at the time? 3 A No. 4 Q Do you see anything 5 improper as President of Lilly Research Labs 6 concerning individuals under your supervision 7 having communications regarding issues of this 8 with public officials? 9 A Absolutely not. 10 Q Would you have any 11 objection to the public being aware of the 12 contents of this memo? 13 A No. 14 Q The memo suggests that 15 you are copied on this correspondence? 16 A Yes. 17 Q Do you recall receiving 18 this? 19 A Yes. 20 Q Do you recall speaking 21 with Doctor Thompson concerning this? 22 A No, I don't recall 23 specifically as a result of receiving this of 24 going to talk with him or having him come to see 158 1 me. 2 Q Do you recall discussing 3 the subject of this memo? 4 A We would have discussed 5 it, yes, at some time when we were together. 6 Q What discussions do you 7 recall having with Doctor Thompson concerning this 8 discussion he had had with Doctor Leber? 9 A There is nothing 10 specific, just a general discussion to sort of 11 fill in between the lines of any other information 12 that was not put into the E-mail, but no 13 specifics. 14 Q Well, the E-mail suggests 15 that Doctor Leber suggested study or studies on 16 the issue of Prozac and suicidality, didn't they? 17 A He did. 18 Q And he suggested several 19 designs, correct? 20 A Yes. 21 Q One was a case control 22 retrospective study developed in concert with 23 Doctor Teicher? 24 A Yes. 159 1 Q And that was not done, 2 was it, Doctor Perelman? 3 A That was not done. 4 Q Why? 5 A Well, for one very good 6 reason, as we discussed that in senior management 7 and with Legal, Legal pointed out that Doctor 8 Teicher was, from all indications they had, almost 9 certainly going to appear as an expert witness for 10 potential plaintiffs, and that it was at their 11 strongest urging that we not proceed to be 12 involved with Doctor Teicher while he would at the 13 same time be appearing as the plaintiffs' expert 14 witness. 15 Q Well, as a scientist, 16 weren't you of the opinion then that a case 17 control retrospective study in concert with Doctor 18 Teicher would be valuable in determining whether 19 or not there was a connection between Prozac and 20 suicide? 21 A I did not feel that 22 Teicher's involvement was at all crucial, but that 23 it would be an added feature and desirable. 24 Nevertheless, the same way that on medical 160 1 questions, Medical dominates over Marketing, on 2 these kind of legal questions, Legal dominates, 3 and it was our considered opinion that we should 4 follow their advice. 5 Q So the lawyers overrode 6 the scientists in connection with doing a case 7 controlled retrospective study with Doctor 8 Teicher? 9 A I wouldn't say overrode, 10 they pointed out the negatives, potential 11 liability of it, and we concluded that given that 12 that what Teicher would add wasn't worth the 13 dangers on the legal side. 14 Q Well, were the scientists 15 of the opinion that a case control retrospective 16 analysis in concert with Teicher be of scientific 17 value on the issue? 18 A As I stated before, we 19 felt that Teicher involvement was by no means 20 crucial, critical to having that sort of study, 21 but that it would be desirable, if possible, to 22 have him involved. 23 Q Had Legal not insisted 24 that this not be done, would it have been done, 161 1 Doctor Perelman? 2 A I can't say with 3 certainty because there was debate back and forth, 4 at the time there were probably more folks leaning 5 toward proceeding, and if for no other reason, 6 that Paul Leber would be more satisfied. 7 Q What was your opinion on 8 this, without the objections of Legal? 9 A I hadn't really come to a 10 strong conclusion. The discussions were still 11 going on, I was weighing -- never having met 12 Teicher and not knowing enough about him, I had 13 not yet weighed whether he would be an impediment 14 or an assist and had not yet formulated my own 15 strong views. 16 Q When was this meeting 17 where there was the question debated concerning a 18 case control retrospective study with Doctor 19 Teicher? 20 A It was plural, it was 21 certainly more than one meeting, whether it was 22 three or whether it was five, it was of that 23 order, and in this sort of time frame, I can't fix 24 it any better than that. 162 1 Q So it would have had to 2 have been after July 18, 1990, it would have been 3 after this suggestion was made by Doctor Leber? 4 A That is my recollection, 5 yes. 6 Q It might have continued 7 for some period? 8 A That's correct. 9 Q Over several discussions? 10 A Yes. 11 Q And who would have been 12 involved in these discussions? 13 A Doctor Herr, Mr. Step, 14 Mr. Wood, myself, Doctor Thompson -- let's see, at 15 this stage, I don't know whether -- I'm not sure 16 when Buck Bradley retired. It was either 17 Mr. Bradley, the general counsel, or his 18 successor, J.B. King, and there may have been -- 19 probably were one or two others, or even not 20 always present at those meetings, but that's the 21 large core group. 22 Q Is that group of 23 individuals known by any special committee name? 24 A It basically was part of 163 1 a -- sort of a Tuesday morning task force. 2 Q Was this the Executive 3 Committee? 4 A No. Certainly a large 5 number of Executive Committee members were on it, 6 but it was not an Executive Committee meeting. 7 Q And by Executive 8 Committee, I mean Executive Committee of the Board 9 of Directors? 10 A That's what I meant, yes. 11 Q Was this an ad hoc 12 committee formed to decide what could be done in 13 respect to these requests made by Doctor Leber of 14 the Food and Drug Administration? 15 A It was a committee, ad 16 hoc in the sense that it hadn't existed before the 17 Prozac issue reached a high profile, and 18 subsequently has disappeared, but it was in 19 existence for a long period of time. 20 Q That was going to be my 21 next question is for how long did this committee 22 exist. 23 A I guess it would be on 24 the order of two years, let's say. 164 1 Q So approximately, say, 2 latter July, early August 1990 until the summer of 3 maybe 1992? 4 A Give or take, roughly. 5 Q Did it continue to meet 6 and discuss this issue after the FDA Advisory 7 Committee meeting in September 1991? 8 A I don't know, I can't 9 recall that. 10 Q Do you recall any 11 meetings or any business that that committee had 12 after September 1991? 13 A Yes. 14 Q Were there any meetings 15 after the results of the Advisory Committee 16 groups? 17 A I believe that our 18 continuing interchange with the wonderful Church 19 of Scientology kept us meeting with some 20 regularity regardless of the -- yes, of the 21 Advisory Committee, yes. 22 Q I'm not a member of the 23 Church of Scientology. 24 A Pardon me? 165 1 Q I'm not a member of the 2 Church of Scientology. 3 A I would have been amazed 4 if a gentleman of your intellect would be. 5 Q Nor are any of my 6 clients, all right? 7 A Good. 8 Q The same to be said of 9 Ms. Zettler. 10 MS. ZETTLER: Especially 11 the intelligence part. 12 Q Additionally, according 13 to this memo, Doctor Leber at the Food and Drug 14 Administration suggested a cohort study where I 15 assume the cohort would be somebody other than 16 Teicher, correct? 17 A Uh-huh. 18 Q Was that what your 19 understanding of the cohort study would be? 20 A (WITNESS MOVES HEAD UP 21 AND DOWN.) 22 Q You have to give an 23 audible answer. 24 A Yes. 166 1 Q That was not done either, 2 was it? 3 A No. 4 Q Why? 5 A When we continued after 6 this communication to discuss amongst ourselves, 7 discuss with outside experts and consultants, and 8 discuss with the FDA, various possible designs of 9 a study that would provide statistically 10 meaningful results and so on, we continued to be 11 stymied of coming up -- we or FDA suggestions with 12 study designs that we were convinced were worthy 13 of undertaking and had reasonable possibility, 14 probability of giving meaningful results. 15 Q I'm no scientist and this 16 stuff is all new to me, but when I see the term 17 cohort study, I get the idea that this is a study 18 that would be a prospective study in nature that 19 you would call in the assistance of other experts 20 or experts in the field, is that right? 21 A Yes. 22 Q Is that your 23 understanding of what was being discussed as a 24 cohort study? 167 1 A Well, my -- that's why we 2 were engaged in not only trying to come up with a 3 trial design ourselves, but were tapping 4 consultant resources, the best people we could 5 identify in the field to help design a study. 6 It's most critical before you start out on such a 7 study to have a trial design that there's a 8 consensus this is an appropriate, adequate design 9 to derive the answers that you're seeking, whether 10 the answer is yes or no. 11 MR. SMITH: Are you okay, 12 John? 13 MR. BRENNAN: Yes, cohort 14 is a term of art in epidemiology, before everybody 15 gets astray, I'll point that out. 16 MR. SMITH: Thank you. 17 MR. BRENNAN: It has 18 nothing to do consultants or anything else; it's a 19 defined term in epidemiology. 20 Q (BY MR. SMITH) The other 21 item addressed by Doctor Leber, or suggested I 22 think is the term Doctor Thompson used, was a 23 larger blind prospective study designed with the 24 help of Teicher detected phenomena, correct? 168 1 A Yes. 2 Q Obviously if Legal said 3 don't use Teicher, you couldn't use Teicher, 4 correct? 5 A Well, if we felt so 6 strongly that it was critical and let the 7 potential weakening of the liability situation be 8 damned, yes, we could have, but we chose, in our 9 collective wisdom, to weigh the pros and cons and 10 not proceed with Doctor Teicher. 11 Q All right. A larger 12 blind prospective study obviously could be done 13 without Teicher, couldn't it? 14 A Yes. 15 Q Teicher is not the only 16 psychiatrist of some prominence in the United 17 States, is he? 18 A No. 19 Q And a large blind 20 prospective study could be done by Lilly without 21 the assistance of Doctor Teicher? 22 A That's correct. 23 Q Was one done? 24 A No. 169 1 Q Why? 2 A As I've indicated, 3 despite our best attempts to devise a protocol, we 4 were unsuccessful, and we had discussions with 5 Paul Leber and he asked questions and made 6 suggestions and neither party reached a point -- 7 party, Lilly and FDA, where it was agreed that 8 there was a design that we could come up with that 9 really held a reasonable chance of answering the 10 question. 11 (PERELMAN EXHIBIT NO. 14 MARKED FOR 12 IDENTIFICATION.) 13 Q (BY MR. SMITH) Exhibit 14 14 is a meeting that was held between Lilly 15 employees and the Food and Drug Administration, 16 almost, well, ten months after the original Leber 17 suggestions, correct? 18 A Yes. 19 Q And you are not copied on 20 this memo, are you? 21 A No. 22 Q There Doctor Kotsanos has 23 written a memo concerning the meeting that 24 occurred on May 13, 1991, right? 170 1 A Yes. 2 Q There apparently Lilly 3 agreed to do the following projects: One, proceed 4 with the rechallenge study, correct? 5 A Yes. 6 Q Have I missed something, 7 as I understand it, you had said that we couldn't 8 do a prospective study, that we had analyzed 9 several things; then if you look at this, it looks 10 like Lilly is already agreeing with the FDA to 11 actually proceed to do a rechallenge study, 12 correct? 13 A Correct, but there's a 14 disconnect. 15 Q Okay, tell me what the 16 disconnect is. 17 A While it's one thing to 18 take a virgin population of depressed people and 19 start treating them with Prozac and waiting to 20 measure the incidence of suicide and suicidal 21 ideation, it's another one to take a population 22 that is reported to have had suicidal ideation and 23 rechallenge them. 24 Q In your experiences 171 1 working with scientists -- you are a scientist 2 with a Ph.D. -- and in dealing with a large 3 pharmaceutical firm, you're familiar with the term 4 rechallenge study, are you not? 5 A I believe so. 6 Q And the idea of 7 rechallenge is sort of like reexposure where an 8 individual that's had one reaction on one 9 particular occasion to a particular compound, say, 10 is then taken off that compound, then restarted or 11 rechallenged with that compound to see if you can 12 evoke the previous response, correct? 13 A That's correct. I 14 believe that's what I just tried to describe. 15 Q Were you in favor of a 16 rechallenge study? 17 A I started out with grave 18 reservations and they remained grave. 19 Q Did you know that Lilly 20 had agreed to do a rechallenge study with the Food 21 and Drug Administration? 22 A Yes. 23 Q And did you know a 24 rechallenge protocol had actually been drafted by 172 1 the scientists at Lilly? 2 A I may have at the time; I 3 don't recall it sitting here now. 4 Q What were your grave 5 reservations about doing it? 6 A The ethics. 7 Q In what respect? 8 A If any of those 9 individuals that had purportedly had suicidal 10 ideations when put on to the study and they had it 11 again and succeeded in actually committing 12 suicide, that's what I mean by the ethics; and 13 secondarily then the legal liability, but the 14 medical ethics of it were very much in question. 15 We're not talking about someone getting a rash. 16 Q Well, obviously suicide 17 is much other serious than a rash? 18 A No question about that. 19 Q And raises much higher 20 ethical questions, correct? 21 A Certain. 22 Q Ethical questions of much 23 greater consequence maybe I should say, correct? 24 A Certainly. 173 1 Q If Prozac caused a 2 particular individual to commit suicide, would 3 that be a serious adverse event? 4 A If it could be shown that 5 indeed it was a causative agent, it certainly 6 would. 7 Q And would that be a 8 significant event as far as Lilly is concerned? 9 A Yes. 10 Q And as far as you are 11 personally concerned? 12 A Yes. 13 Q And do I take it by that 14 that it would not take more than one suicide to be 15 of significance to Lilly in evaluating the safety 16 of the product if it could be established that 17 Prozac caused that suicide? 18 A Yes, significance 19 relative to what, though? Significance, 20 significant, different things -- penicillin causes 21 deaths and is still used. I'm not drawing a 22 direct analogy there, but there are products on 23 the market that are known to cause deaths. So, 24 yes, significant, any time a life is lost or a 174 1 serious injury, it's significant. 2 Q What's done generally in 3 connection with those products that cause death? 4 A What is done? 5 Q Yes, by the 6 manufacturer. 7 A It depends on the 8 circumstances. 9 Q Well, what the 10 manufacturer does is warn that there is a risk of 11 a potential death that arises out of the use of 12 the product? 13 A Yes, but in cases where 14 the occurrence is not a recognized and frequent 15 sequelae of the disease itself, that's a somewhat 16 different situation and I don't see the analogy 17 here in the case of where the deaths occur, but 18 there's a very high death level from suicide 19 itself caused by the disease, not by the drug. 20 Q I understand that it is 21 your position that the Prozac doesn't cause 22 suicidality, or has caused any particular 23 individual to commit suicide, and I'm not going to 24 argue with you about that. My point is, is that 175 1 in connection with other drugs that may have some 2 medical usefulness but have a medical risk, 3 generally what is done in that situation is that 4 the manufacturer of that product warns of the 5 existence of that risk, correct? 6 A Correct. 7 Q And that is proper for 8 the pharmaceutical manufacturer to do in those 9 instances? 10 A Yes. 11 Q Do you know Doctor 12 Kotsanos? 13 A Yes. 14 Q Doctor Kotsanos says in 15 the third bullet point under Point 1 in connection 16 with proceeding with the rechallenge study that, 17 "We have agreed to have the rechallenge protocol 18 ready to go by September 1, 1991, and to provide 19 data after the first quarter which would provide 20 information on six months of experience," correct? 21 A Yes. 22 Q The rechallenge protocol 23 wasn't ready to go by September 1, 1991, correct? 24 A I don't recall that 176 1 specifically, but -- 2 Q Well, the testimony is 3 it's never been done. 4 A But that doesn't mean the 5 protocol wasn't ready, per se. If you tell me 6 that it is and there's some evidence that it was 7 not ready, I'll accept it, but because the study 8 wasn't done doesn't mean the protocol wasn't 9 ready. 10 Q All right. Well, the 11 protocol wasn't implemented in a clinical trial? 12 A Clearly. 13 Q Where data was collected 14 as is discussed in this bullet point? 15 A That is correct. 16 Q Why was that? 17 A I thought I covered that 18 in indicating that in our discussions we concluded 19 that the ethics issue was overriding and that we 20 were not prepared to undertake that study. 21 Q All right. When was that 22 decision made that where you decided the ethics 23 issue was overriding? 24 A Sometime subsequent to 177 1 May 15, 1991. 2 Q But before September 1, 3 1991? 4 A I can't fix it. I'm not 5 sure why you've picked September 1. Sometime 6 after May 15, 1991. 7 Q I picked September 1 8 because under this bullet point it says, "We 9 agreed to have the rechallenge protocol ready to 10 go by September 1, 1991 and to provide data after 11 the first quarter which would provide information 12 on six months of experience." 13 A That doesn't lead me to 14 clearly conclude that it was prior to September 15 1. We may have had all kind of variety of 16 interactions with FDA and delayed that, and so I 17 just don't know, I don't recall. All I can say is 18 it was after May 15. 19 Q Was there an agreement by 20 Lilly to do the protocol and a protocol submitted, 21 but than later these ethical considerations 22 overrode the decision to do the protocol? 23 A I'm not clear that the 24 protocol was formally submitted. 178 1 Q All right, let me give 2 you this to help you in that connection. 3 (PERELMAN EXHIBIT NO. 15 MARKED FOR 4 IDENTIFICATION.) 5 A All right, without even 6 reading further, it's clear from the introductory 7 paragraph that it was submitted as of April 17, 8 and that would suggest we would not have submitted 9 it -- logically suggest, if indeed we were not 10 going to do the study, so I must conclude that our 11 decision not to proceed postdated April 17, 1991. 12 Q Was this decision not to 13 proceed made by this ad hoc committee that you 14 described to me? 15 A Yes. 16 Q Do I take it by that that 17 the decision to submit the protocol and to 18 originally proceed was made by that same ad hoc 19 committee? 20 A Not necessarily, no. 21 Q Tell me why there's a 22 distinction there. 23 A Well, Medical conducts a 24 lot of important business without needing to run 179 1 it past some higher committee, and they may not 2 have chosen or elected to query the committee 3 before submitting the proposal, I just don't know, 4 but it's one of many items of importance that 5 Medical is authorized to conduct under its own 6 authority. 7 Q When did you first become 8 concerned about the ethics of doing the 9 rechallenge study? 10 A When it surfaced in that 11 committee. 12 Q Had it surfaced before 13 April, the date of Exhibit 15? 14 A Surfaced, to my 15 knowledge, the best of my recollection, it didn't 16 surface until it came into that ad hoc committee. 17 Q So when did it come in, 18 or is that what we're having problems knowing as 19 to when? 20 A Yes, I said there were 21 several meeting where that was discussed in that 22 committee and I just can't fix dates. 23 Q Were there notes made by 24 members of that committee? 180 1 A I don't know. 2 Q Were there minutes kept 3 of the deliberations of that committee? 4 A I don't believe there 5 were; to my recollection, there was not a 6 secretarial function. 7 Q Were there members of the 8 committee that were in favor of doing a 9 rechallenge protocol? 10 A Well, when first 11 presented, the Medical representation talked 12 about, from a scientific medical point of view, 13 the possible virtue and would give more -- it had 14 a higher likelihood of giving more clear-cut 15 answers. 16 Q Okay, so Medical advised 17 or members of Medical who were on the ad hoc 18 committee indicated that the rechallenge study 19 would be scientifically valid or significant in 20 addressing the issue, is that correct? 21 A Yes, that's correct. 22 Q Of those members of the 23 committee that you mentioned, as far as I know 24 only Leigh Thompson would have been in Medical at 181 1 time? 2 A Yes. However, depending 3 on the subject matter, the agenda, guests would 4 come in, and from time to time some of Leigh's 5 colleagues would come into a meeting. 6 Q Did you know in May that 7 Medical had agreed to do a rechallenge study? 8 A If that was an item of 9 discussion in that ad hoc committee by then, I 10 would have known from that regular meeting, 11 Tuesday morning meeting. 12 Q Exhibit 14 also indicates 13 that there would be a incorporation of a Modified 14 Scale for Suicidal Ideation in ongoing and planned 15 US and UK clinical trials, does it not? 16 A Yes. 17 Q Do you know if that was 18 done? 19 A No, I don't. 20 Q It suggests that the 21 Modified Scale for Suicidal Ideation Revised be 22 used in hospitalized patients being treated for 23 depression to validate and determine if the 24 phenomena exists in seriously ill patients. Do 182 1 you know if that was done? 2 A No, sir, I do not know. 3 Q Apparently Lilly also 4 agreed to do a descriptive study of patients 5 reported to develop intense violent suicidal 6 thoughts, Item 4? 7 A Item 4, all right. 8 Q Do you see that? 9 A Uh-huh. 10 Q Is that a yes? 11 A Yes, it is, I do see it. 12 Q Was that done? 13 A I do not recall that it 14 was done. 15 Q Would you have had any 16 objection to that? 17 A I would have to have a 18 refresher as to what the protocol intent of the 19 study would be, the nature of the study. 20 Q Do you recall it being 21 presented to you in any fashion and recall any 22 objection that you might have had at the time? 23 A My recollection was 24 concern along this same line of the question of 183 1 ethics. 2 Q Well, how does ethics 3 arise in Point 4 in connection with descriptive 4 studies? 5 A Oh, I'm sorry, let me 6 read that part of the paragraph again. It 7 wouldn't unless the pilot study involved such 8 patients, but again I don't know whether the 9 study -- any part of the study was done or not, I 10 simply don't recall that it was. 11 Q Would you have had an 12 objection to a pilot in-hospital rechallenge study 13 or an inpatient pilot study using a rechallenge 14 protocol? 15 A I can't answer yes or no 16 without a lot of detail about the control of the 17 protocol, the supervision and so forth. 18 Q Let's assume that the 19 patients were adequately supervised and that you 20 could insure that you could prevent harm actually 21 coming to a patient under study. 22 A Provided that my medical 23 colleagues in the art would not point out any 24 shortcomings or deficiencies, recognizing that I'm 184 1 not qualified to practice medicine, I probably 2 would be disposed to let it go forward. 3 Q I don't remember what you 4 said, and I may have asked you this Doctor 5 Perelman, did you have any objection to the MSSI-R 6 questionnaire being administered in the depression 7 trials that were ongoing? 8 A I don't believe you asked 9 me that, and no, I didn't have any problem with 10 that. 11 Q Do you remember that 12 being presented as an option to analyze this issue 13 with respect to whether or not Prozac was related 14 to suicide or violent aggressive behavior? 15 A I remember only 16 discussion of a possible different rating system, 17 but nothing specific beyond that. 18 Q Were there several 19 different rating systems presented to you? 20 A Several -- two or three. 21 Q Do you recall having any 22 problem with any one of those systems yourself? 23 A No. 24 Q I would assume this would 185 1 have to be something you would rely on the 2 psychiatrists to guide you on in connection with 3 the specifics of these things? 4 A Absolutely. 5 Q Look with me at the -- I 6 think it's the last sentence of the next to the 7 last paragraph of the May 13 memo? 8 A May 13? 9 Q Yes, I think you got it 10 there. 11 A Okay -- all right, it 12 just said it was May 15 on the top of the page, 13 but it's a May 13 Protocol and it's May 13 headed 14 on the second page, right. 15 Q It says Doctor Leber also 16 had concern about the rechallenge study in that 17 patients who had previously been exposed to the 18 drug and had suicidal symptoms may be biased on 19 the redevelopment of such symptoms and treatment, 20 which is why he made the suggestion to look at the 21 incidence in garden variety depressed patients 22 treated with these agents for the first time. 23 A Uh-huh. 24 Q Do you see that? 186 1 A Yes. 2 Q Did that seem like a 3 reasonable suggestion to you? 4 A It did until we looked at 5 actually designing the protocol, the size of the 6 study, and given the great frequency of suicide 7 and suicidal ideation in depressed patients, we're 8 right back to where we were before of not being 9 able of putting our best efforts into it, in-house 10 experts, out-of-the-house consultants, interaction 11 with FDA, to indeed come up with a meaningful 12 study of practical scope calculated to give a good 13 possibility of a meaningful answer, and that is 14 the reason why, to my recollection, the study did 15 not go forward. 16 Q Is the fact that the 17 matter was brought before the Advisory Committee 18 of the Food and Drug Administration and the 19 Advisory Committee made findings favorable to 20 Lilly's position in connection with the matter 21 have anything to do with the decision not to do 22 any of these studies mentioned? 23 A No, sir. 24 Q That memo also mentions 187 1 that Doctor Leber had asked -- or the FDA had 2 mentioned whether or not Lilly was planning to 3 develop a ten-milligram dose, correct? 4 A Yes. 5 Q Had the Food and Drug 6 Administration expressed a desire that Lilly 7 develop a ten-milligram dose of Prozac? 8 A As I recall specifically, 9 Doctor Leber raised the question about a 10 ten-milligram dose rather than just being, quote, 11 the Food and Drug Administration. 12 Q As I understand it, 13 either Mr. Bradley or Mr. King, your general 14 counsel, had advised that the prospective study 15 with Doctor Teicher should not be done, correct? 16 MR. MYERS: Doctor 17 Perelman, don't disclose anything that you 18 discussed with any lawyer from Lilly inside or 19 outside, don't say anything more about discussions 20 with any lawyer. 21 MR. SMITH: I think he's 22 already mentioned it. 23 MR. MYERS: He's not 24 going to discuss anything further about any 188 1 discussions with any lawyers. I instruct him not 2 to answer that. 3 MS. ZETTLER: Certify it. 4 (QUESTION CERTIFIED.) 5 Q (BY MR. SMITH) Was 6 Mr. Bradley or Mr. King involved in all these 7 discussions that this ad hoc committee on 8 suicidality had? 9 MR. MYERS: You can 10 answer that. 11 A First of all, it's 12 incorrect to characterize it as an ad hoc 13 committee on suicidality; it was an ad hoc 14 committee on Prozac involving all aspects of 15 Prozac, including the Church of Scientology and 16 their attacks, and so it's important, I think, to 17 correct that. And yes, either one or the other, 18 or if one was out of town, they would send some 19 other legal counsel to all of those meetings 20 invariably. 21 Q What matters did the ad 22 hoc committee address in connection with Prozac 23 other than Prozac and suicidality and Prozac and 24 the media problems that had been created by virtue 189 1 of that? 2 A The whole cafeteria from 3 the question of the ten-milligram dosage, do we 4 want it or not, the liquid dosage form, do we want 5 it or not, or anything else related to the 6 marketing of Prozac, the issue of the new 7 competing products coming along, A to Z related to 8 the product Prozac. 9 Q But I take it that this 10 was a special group that these matters with other 11 products, that is marketing, changing dosage, 12 things of that nature, would normally be carried 13 out in the normal corporate routine, is that 14 correct? 15 A Normally, but there are a 16 number of other instances where similar ad hoc 17 committees were formed, so it was not a singular 18 event. 19 Q Well, give me an example 20 of another instance where a committee such as this 21 would be born? 22 A Human insulin, Humulin, 23 which was a major potential product of great 24 interest to the company, and senior management 190 1 decided we wanted to track everything related to 2 the late stages of development and manufacturing 3 and marketing of Humulin around the world and any 4 issues related to it from pricing to safety to 5 efficacy. 6 Q Of this committee in 7 connection with Prozac, was there one individual 8 who took more responsibility than any others as 9 far as the day-to-day activities of this pursuit? 10 A I'm not sure, would 11 you -- 12 Q It's probably a bad 13 question. 14 A -- state the question 15 again, please? 16 Q Obviously each of you 17 gentleman that were on this committee had other 18 duties in connection with corporate business on 19 other products of the corporation. 20 A Yes. 21 Q Was there someone who 22 took it as their responsibility to be primarily 23 responsible for this? 24 A Yes, I would say Gary 191 1 Tauscher was serving as the coordinator and 2 secretary and spent pretty well full time and 3 would schedule the meetings, and although perhaps 4 among the more junior people present, was the 5 individual that had that role. 6 Q Gary Tauscher certainly 7 wouldn't be considered senior management? 8 A That's correct. 9 Q Of those members of the 10 committee that were senior management, was there 11 one taking more active day-to-day activity in this 12 product than others? 13 A Leigh Thompson would be 14 on the medical side, FDA side, regulatory side, 15 and Gene Step for the marketing aspects. 16 Q Go back with me, Doctor 17 Perelman, to Exhibit 13. On Page 2 there's a 18 discussion that -- Page 2, first full paragraph, 19 this would be the second paragraph where he says 20 he then said that Temple -- 21 A Yes. 22 Q "He," assuming Doctor 23 Leber, "then said that Temple had asked that we 24 not effect label changes on the suicide issue 192 1 without clearing them with the FDA first. I think 2 Paul would like this in general, but emphasized 3 Bob's interest specifically on the suicide issue. 4 There wasn't anything else that hinted to more 5 need for label change. I promised we would on 6 suicide not use the provision for effecting the 7 change," correct? 8 A Yes. 9 Q Were there discussions in 10 July 1990 in connection with potentially 11 changing -- making label changes on Prozac and the 12 suicide issue? 13 A I don't know about the 14 suicide issue, but we had made and were continuing 15 to make, with some frequency, label changes as we 16 gathered more marketing experience with Prozac. 17 Q Well, obviously as more 18 adverse events occurred, as I understand it, FDA 19 regulations require that those be added to the 20 label in connection with frequency, is that right? 21 A Well, that's kind of the 22 easy part. There are also the issue of seeing in 23 general usage an occurrence that you didn't see in 24 clinical trial and do you put it into the package 193 1 insert, and if so, in what section of the package 2 insert, and it was more of the latter that I was 3 referring to. 4 Q All right. And are you 5 saying that there were or were not discussions 6 concerning effecting label changes vis-a-vis 7 suicide at this time? 8 A I'm saying that I can't 9 fix the date in which those discussions took 10 place, that already by this time we had taken the 11 initiative without FDA requesting it to make other 12 types of label changes, and with regard to 13 suicidality, I can't fix the time and say yes or 14 no to your question is what I'm saying. 15 Q All right. Is it correct 16 that Lilly can make label changes without 17 permission from the FDA? 18 A We advise them that we 19 are proceeding, and in the end they really need to 20 agree, but we have taken the initiative in these 21 cases and said here's our data and here's a label 22 change we're proposing to make, and that's what is 23 being referred to. 24 Q If Lilly wanted to make a 194 1 label change to the effect that Prozac in some 2 individuals has been reported to cause suicide or 3 suicidal ideation and/or violent aggressive 4 behavior, whether or not this is indeed an 5 activity or action caused by Prozac, these reports 6 should be kept in mind by the practitioner in 7 making the decision in connection with respect to 8 whether or not to prescribe Prozac, end quote, 9 could Lilly make a change such as that without 10 getting FDA approval? 11 A I would urge you to ask 12 that question of someone in the regulatory area. 13 It is my understanding that we do not have freedom 14 to make those kind of changes without an agreement 15 by FDA as to content and specific wording. My 16 experience has been they have gotten to word 17 craftsmanship very, very -- in minute detail 18 sometimes. 19 Q But Lilly can make 20 suggestions to the Food and Drug Administration? 21 A Oh, yes. 22 Q Concerning additional 23 warnings, precautions and contraindications with 24 respect to their product? 195 1 A And that's what I had 2 indicated earlier we had done proactively, gone to 3 the FDA and say we're proposing to introduce some 4 further changes. 5 Q On your being proactive 6 and suggesting label changes on suicide? 7 A No. 8 (SHORT BREAK TAKEN.) 9 Q (BY MR. SMITH) Doctor 10 Perelman, the next to the last paragraph of what 11 we referred to as the Leber memo, Exhibit 13 -- 12 A The next to the last? 13 Q Yes, sir. It reads, 14 "Paul is taking" -- and I assume that is Paul 15 Leber? 16 A Yes. 17 Q "Paul is taking a 18 position in talking with outside folks today that 19 Lilly and FDA and working together on the suicide 20 issue and following closely the post-marketing 21 events, but that there are no denominators and the 22 best that can be done is to put a cap on the 23 number of events," correct? 24 A Yes, that's how it reads. 196 1 Q Did you ever discuss this 2 aspect of Doctor Thompson's conversation with 3 Doctor Leber with Doctor Thompson? 4 A I don't recall that, no. 5 Q Had you noticed this 6 paragraph in this memo? 7 A I'm sorry. 8 Q Before today. 9 A Oh, I would have, upon 10 receiving it, would have read the memo, yes, 11 certainly, including that paragraph. 12 Q Did that strike you as 13 significant at the time? 14 A I can't recall how it 15 struck me at the time. It hasn't left a lasting 16 impression, obviously, and -- 17 Q Do you know of any effort 18 done by Eli Lilly and Company to put a cap on the 19 number of post-marketing events in connection with 20 the suicide issue? 21 A I can't begin to 22 understand what the statement means, so I'm quite 23 puzzled. One would have to talk with Doctor 24 Thompson to explain what that phrase or sentence 197 1 means. 2 Q No, my question to you, 3 Doctor Perelman, is do you know of any efforts on 4 behalf of Eli Lilly and Company to put a cap on 5 the number of post-marketing events that have 6 arisen in connection with suicide? 7 A Not only do I not have a 8 clue what is meant by cap in this case, no is the 9 answer as well. 10 Q So the answer to my 11 question is no? 12 A That's correct. 13 Q You don't know of any 14 effort on the part of Lilly to limit the number of 15 adverse events reported on suicide? 16 A That is correct, and in 17 pointing out that I don't know that cap means 18 limit in this instance. I don't know, it's 19 baffling, but no, we definitely did not ever have 20 any discussions or put any kind of cap on the 21 number of events in the sense of it being a limit. 22 Q Do you agree with me that 23 it's not an unreasonable interpretation of the 24 word cap there to use the same name limit? 198 1 A I agree and it's puzzling 2 that it's in quotation marks, however, and if it 3 was cap in the sense of limit, I don't understand 4 that it requires quotation marks, I'm baffled, but 5 we did not limit any number of events. 6 Q Are you aware of any 7 relationship that could be construed as an 8 improper relationship between Eli Lilly and 9 Company and the Food and Drug Administration? 10 A No, sir. 11 Q Are there any internal 12 connections in place that you know of that Lilly 13 has with the FDA? 14 A I don't understand 15 internal connections. 16 MR. FREEMAN: Clarify. 17 Q Any inside connection 18 that gives you any advantage over competitors. 19 A No. 20 Q Any inside connection 21 that gives you any slack in complying with FDA 22 regulations? 23 A Absolutely not. 24 199 1 (PERELMAN EXHIBIT NO. 16 MARKED FOR 2 IDENTIFICATION.) 3 Q (BY MR. SMITH) Doctor 4 Perelman, Exhibit 16 I'll represent to you is a 5 document that we received from Lilly that 6 purportedly comes from your file. Is that your 7 handwriting on the upper right-hand corner of that 8 page? 9 A No, it is not. 10 Q Have you ever seen 11 Exhibit 16 before? 12 A I believe I have, yes. 13 Q That document reflects 14 some communications with individuals at the FDA in 15 connection with Prozac liquid, does it not? 16 A Yes, it does. 17 Q And this is one of the 18 reasons for my question to you concerning internal 19 connections. 20 A Uh-huh. 21 Q At top of that 22 document -- 23 A Uh-huh. 24 Q -- under the Comments 200 1 section, it says, "Looks like internal connections 2 now in place within FDA. Know of no reason why 3 there should be any remaining issues on M/C side," 4 correct? 5 A Yes. 6 Q What is the M/C side? 7 A Manufacturing and control 8 segment of the New Drug Application. There's a 9 medical and so forth. 10 Q Do you know of any 11 internal connections that Eli Lilly has with the 12 FDA in connection with manufacturing and control 13 of Prozac liquid? 14 A I don't know of any 15 specific internal connections. This would 16 indicate that Bill Grosse feels that such have 17 been established in this particular case. 18 Q Is it Bill Grosse that 19 wrote the comments there? 20 A Oh, I'm sorry, John 21 Lechleiter would have been the source of the 22 comments, Bill Grosse is the source of the 23 document between the dotted lines. 24 Q Okay, who is John 201 1 Lechleiter? 2 A John Lechleiter at that 3 time was an Executive Director in Pharmaceutical 4 Development, now a vice president. 5 Q Did you ever talk to 6 Mr. Lechleiter concerning any internal connections 7 that Lilly might have had within the FDA? 8 A Absolutely no reason to, 9 very much above board and the sort of connections 10 that one tries to establish, linkages in order to 11 have good communications, no nefarious 12 implications whatsoever. 13 (PERELMAN EXHIBIT NO. 17 MARKED FOR 14 IDENTIFICATION.) 15 A I've really just scanned 16 it without reading every word, in view of the 17 detail and complexity of Co-Start terminology and 18 so on; if necessary I'll go back and read it line 19 by line. 20 Q All right. It appears 21 that Exhibit 17 is an E-mail from the German 22 affiliate to Indianapolis, correct? 23 A Yes. 24 Q Do you know Hans Weber? 202 1 A Yes. 2 Q Do you know Claude 3 Bouchy? 4 A Yes. 5 Q Who is Claude Bouchy? 6 A He is originally French, 7 came from the French affiliate, and at this time I 8 believe was the General Manager of the German 9 affiliate, or might be at this time. He was still 10 the Marketing Director and Gerhart Meyer was the 11 General Manager. He was either the Pharmaceutical 12 Marketing Director or the General Manager of the 13 German affiliate because he was in one post and 14 moved to the other and I can't fix the time. 15 Q Is Bouchy a medical 16 doctor, as far as you know? 17 A No, he's an MBA, Master 18 of Business Administration. 19 Q But Hans Weber is a 20 medical doctor? 21 A That's correct. 22 Q Do you know where 23 Mr. Bouchy is now? 24 A No, I've lost track, I 203 1 don't. 2 Q Is he still with Lilly? 3 A I'm not even sure of 4 that. 5 Q Did you work with 6 Mr. Bouchy when you were the Director of 7 International? 8 A When I was President of 9 International, Claude was a promising young 10 employee in France. 11 Q And obviously you worked 12 with Hans Weber? 13 A Not closely, but yes, 14 I've interacted with him in meetings. 15 Q Do you respect Doctor 16 Weber in his judgment? 17 A Oh, yes. 18 Q This E-mail concerns 19 adverse event reporting in connection with 20 suicides on Prozac, correct? 21 A Yes. 22 Q And it says that "Hans 23 Weber and I have problems with the directives our 24 safety people are getting from the corporate group 204 1 (Drug, Epidemiology Unit) and requesting that we 2 change the identification of events as they were 3 reported by the physicians," correct? 4 A That's the way it reads, 5 yes. 6 Q Were you aware that the 7 safety people were requesting foreign affiliate 8 physicians to change the identification of events 9 as they are reported by the physicians? 10 A To my recollection this 11 came to my attention when this exchange took place 12 and someone briefed me that there was this 13 exchange going on, and that was my first awareness 14 of it. 15 Q Who briefed you on this? 16 A It would have been either 17 Allan Weinstein or Leigh Thompson, I don't know 18 which of the two. 19 Q What did they explain to 20 you was going on? 21 A That the affiliate from 22 their vantage point understandably had a reaction, 23 a mode of reaction of this type because they 24 weren't aware of the more complete story and the 205 1 reasons why and that it would be worked out. 2 Q Was it worked out? 3 A Yes. 4 Q And how was it worked 5 out? 6 A I really today can't tell 7 you whether the corporate DEU unit preferred 8 approach prevailed or not. 9 Q Well, let me go through 10 with you these two instances that this physician 11 in Germany is mentioning. Number one, he 12 indicates in the second paragraph, "On this one, 13 our safety staff is requested to change the event 14 term suicide attempt as reported by the physician 15 to overdose," correct? 16 A Yes. 17 Q All right. Now, as, at 18 the time, President of Lilly Research Laboratories 19 and a member of the Board of Directors of Eli 20 Lilly and Company, would you have a judgment 21 concerning whether or not that should be done? 22 A No, not absent a 23 discussion regarding what the details were and why 24 that was being requested. I wouldn't 206 1 automatically feel that that was inappropriate. 2 There are insufficient facts available to me here 3 to make that judgment, then or now. 4 Q Are you telling me that 5 then, when it was reported to you, and now as you 6 sit here, you didn't object to changing the event 7 term suicide attempt to overdose? 8 A I left it in the hands of 9 the people in the corporate unit here involved to 10 continue to work with the German affiliate and 11 determine what was the appropriate and correct 12 course of action. 13 Q I guess my question to 14 you is what did you feel at the time was the most 15 appropriate and direct course of action. 16 A That there be 17 discussions, as there were, to determine what all 18 the facts were and resolve it by mutual 19 agreement. I want to repeat myself again that 20 given what is contained herein and a 21 disinclination to assume that there is something 22 underhanded or nefarious going on, it's time for 23 dedicated people to work out the problem through 24 discussion. 207 1 Q All I can read is what's 2 been provided to me, Doctor Perelman; that's one 3 reason I'm asking you about this. Because I want 4 to ask about it at this time, obviously all we can 5 do is try to reconstruct what was happening based 6 on asking you and we're going to ask all of the 7 individuals who were involved in this about this. 8 My questions don't have any implication with 9 respect to being nefarious or not. I just see 10 written here that the term suicide attempt is 11 being directed to be changed to overdose, okay? 12 A Right. 13 Q Then I see following this 14 that corporate Indiana is requesting that your 15 German affiliate change the term suicidal ideation 16 to depression, correct? 17 A Yes, and at the same time 18 there is a rather lengthy missive from Leigh 19 Thompson understanding where they're coming from 20 and attempting to explain, apparently, the reasons 21 why, but I would suggest that Leigh Thompson and 22 Allan Weinstein can be much more responsive than I 23 can from my vantage point. 24 Q All right, we all can 208 1 read what Doctor Thompson said in response to 2 this; then we can all read what Doctor Weber and 3 Mr. Bouchy said in response to what Doctor 4 Thompson had said, correct? 5 A Right. 6 Q And it appears that this 7 is the end of it, that Mr. Bouchy has gotten back 8 and has said, "Thank you very much for your prompt 9 answer and your explanation. Hans and I have 10 rediscussed the issue in depth. Our point is the 11 physician has reported a suicide attempt, do we 12 have a right to change it to some terminology 13 which we may consider to be more specific, e.g. 14 overdose, but which is not free from ambiguity and 15 could be regarded as inaccurate or misleading," et 16 cetera, et cetera. And then it goes on to talk 17 about, "Finally on a very simple and nonscientific 18 basis, I personally wonder whether we are really 19 helping the credibility of an excellent ADE system 20 by calling what a physician is reporting as 21 suicide ideation. We fully realize that there is 22 no code in our DEN system for suicide ideation but 23 it could be argued by people who have little 24 sympathy for the company or by regulatory 209 1 authorities that it is not a responsible way to 2 deal with an issue which is getting so much 3 attention in the scientific and in the general 4 press," end quote. Correct? 5 A Yes. 6 Q Now, basically that's all 7 we have, Doctor Perelman, is this; we don't have 8 any follow-up memos concerning whether or not this 9 situation was resolved, how it was resolved, and 10 whether or not there was or was not anything, as 11 you say, nefarious or not nefarious about it. My 12 question to you is, you say it was brought up to 13 you that there was a discussion there and that you 14 directed, as the President of Lilly Research 15 Laboratories, that they get together and work it 16 out, is that right? 17 A No, I didn't say that, 18 they were -- 19 Q Don't let me say that if 20 you didn't -- 21 A They mentioned it to me 22 because of the fact that there was this difference 23 of opinion and view going on and indicated that 24 they were in the process of discussions back and 210 1 forth. I didn't have to direct anything, the 2 folks were already working back and forth. 3 Q Okay. Do you know of how 4 this problem was resolved? 5 A I would have at the time, 6 I cannot replay it now. 7 Q Do you recall that it 8 just came up in that one instance and then you 9 didn't hear about it after that one time? 10 A No, I recall that there 11 were perhaps about three instances where I was 12 subsequently updated a couple of additional times 13 as the discussions went back and forth, including 14 telephone calls in addition to E-mail. 15 Q Telephone calls between 16 who? 17 A Indianapolis and Bad 18 Homburg, Germany. 19 Q Obviously it would be 20 Weber and Bouchy in Bad Homburg. Who would have 21 been involved in Indianapolis? 22 A Speculation. Presumably 23 one or more of the players listed here 24 Indianapolis based, but I don't specifically know. 211 1 Q Sidney Taurel is listed 2 on the first page of this. 3 A Yes. 4 Q Sidney Taurel is -- 5 A At this time he would 6 have been -- he was my successor as President of 7 International. In 1990, I think he would still -- 8 yes, he would be President of International. 9 Q Was he on the Board of 10 Directors of Eli Lilly and Company at the time? 11 A No. 12 Q Has he ever been? 13 A He is now. 14 Q He is now? 15 A Yes. 16 Q Is he still with Eli 17 Lilly and Company? 18 A Yes. 19 Q In what capacity? 20 A He is president of the 21 global pharmaceutical business. 22 Q Lilly has on numerous 23 occasions in the past submitted reports of experts 24 concerning adverse events in connection with 212 1 Prozac to the Food and Drug Administration, have 2 they not? 3 A Yes. 4 Q Is it, as far as you 5 know, a policy to submit all reports of experts 6 consulted by Lilly in connection with adverse 7 events to the United States Food and Drug 8 Administration? 9 MR. FREEMAN: The 10 question is confusing. Do you mean a report made 11 by an expert to us of an event? 12 MR. SMITH: Yes, or a 13 report made to you by an expert hired to review 14 the occurrence of an event. 15 MR. FREEMAN: Let's deal 16 with one question at a time. 17 A The answer to the first 18 one is yes, and as I understand the first part of 19 the question, it was if we got a report of an 20 adverse event; in other words, a first time 21 report. Assuredly that would be submitted to the 22 FDA, whether it was an expert or not an expert. 23 With regard to whether in 24 all cases where we might engage an expert to do an 213 1 assessment of a group of events, I'm not sure. I 2 don't know the answer to that, as to whether we 3 would or did. If the law requires it, I'm sure we 4 did, or the regulation, but I'm not at all 5 comfortable that that is required and not at all 6 comfortable to say yes, we always have. 7 Q I'm just wondering what 8 Lilly's policy is on when you hire a consultant to 9 review the occurrence of a particular series of 10 adverse events, with respect to whether or not 11 that's submitted to the Food and Drug 12 Administration. 13 A We, to my knowledge, 14 don't have a separate written policy that we would 15 do it if it was required by regulation, we 16 probably would not invariably if it is not. It 17 depends on the nature of the event and what's 18 being analyzed. 19 (PERELMAN EXHIBIT NO. 18 MARKED FOR 20 IDENTIFICATION.) 21 Q (BY MR. SMITH) Exhibit 22 18 is one of a series of documents that apparently 23 you were routinely copied in on which was provided 24 to us out of your file. From MT, I would assume 214 1 that would be Max Talbott? 2 A I would too, yes. 3 Q With a Prozac update, it 4 looks like he's reporting to various individuals 5 on a regular basis in connection with the progress 6 of Prozac through the regulatory process? 7 A Yes, since it says Prozac 8 Update, December 24, January 5. 9 Q He says there, "Today we 10 are submitting the report from one of the 11 consultants on rash." 12 A Uh-huh. 13 Q Is that a yes? 14 A Yes, it is, sorry. 15 Q And I give you that just 16 to give you an example of where Lilly had hired a 17 consultant on rash and that consultant report had 18 been submitted to the Food and Drug 19 Administration. Would you agree that that's what 20 that indicates occurred? 21 A Yes, sir. 22 Q I'm going back now to the 23 1985 document -- 24 MR. FREEMAN: Which 215 1 exhibit is that? 2 MR. SMITH: Which is 3 Exhibit 4. 4 Q (BY MR. SMITH) Where 5 there is discussion of an opinion of twenty-one 6 typewritten pages in connection with the 7 registration of Prozac in Germany, correct? 8 A Yes. 9 Q Where there were issues 10 raised with respect to Prozac and suicide, 11 correct? 12 A Yes. 13 Q And I don't recall 14 whether you said or not that this consultant's 15 report would be submitted to the FDA. I think you 16 said you don't know whether it was submitted to 17 the FDA. 18 A That's my recollection of 19 what I said. 20 Q That's what brings me to 21 the question of did Lilly have a policy on 22 submitting consultant's reports to the FDA -- 23 A Yes. 24 Q -- because I see here 216 1 where Lilly definitely submitted a consultant's 2 report on rash several years later because I have 3 evidence by Doctor Talbott that it was submitted, 4 but I don't have any evidence one way or the other 5 with respect to the consultant on the Germany 6 registration issue that raised the issue of 7 suicide. Do you follow what I'm saying? 8 A Yes, I follow what you're 9 saying. 10 Q Can you help us at all 11 concerning whether or not this foreign -- Doctor 12 Herrmann I believe his name was -- expert report 13 would have been submitted to the FDA by virtue of 14 some policy that might have been in place? 15 MR. FREEMAN: He's 16 already answered that he doesn't know. 17 A I have indicated that I 18 don't know whether this was submitted. I also 19 indicated that I am not aware of a policy and that 20 I'm not aware that it's an FDA regulation or 21 requirement, and that we might submit in some 22 cases and not in others depending on 23 circumstances. That's really repeating what I've 24 said before, I believe. 217 1 (PERELMAN EXHIBIT NO. 19 MARKED FOR 2 IDENTIFICATION.) 3 Q (BY MR. SMITH) Exhibit 4 19 comes with a cover memo of August 31, 1990, 5 correct? 6 A Yes. 7 Q Authored by Doctor David 8 Wheadon? 9 A Right. 10 Q And apparently there was 11 a meeting between Doctor Wheadon and some expert 12 consultants in Europe with respect to the issue of 13 Prozac, treatment and suicidal ideation and 14 behavior? 15 A Yes. 16 Q In the first paragraph of 17 that report it says prior to the visits, the 18 consultants received a copy of the report, quote, 19 Suicidality, end quote, paren, Section VIII, 20 Fluoxetine Safety Experience Summary, submitted to 21 the FDA July 18, 1990, close paren, correct? 22 A Yes. 23 Q Were you aware that Lilly 24 had submitted a report to the FDA on suicidality? 218 1 A I would have been at the 2 time, yes. 3 Q Now, was that report a 4 report where consultants were used to discuss the 5 issue? 6 A I today do not know the 7 answer to that. 8 Q But at least in August of 9 1990, Lilly was submitting to the FDA or had 10 submitted to the FDA their report on suicidality, 11 had they not? 12 A Yes. 13 Q Do you know if that 14 report contained the twenty-one-page typewritten 15 report done by Professor Herrmann back in 1984 16 or '85? 17 A I believe for the third 18 time, I do not know whether that report has ever 19 been submitted, let alone whether -- 20 Q I thought that maybe 21 bringing you up to a 1990 suicide report may help 22 you. 23 A No, sir. 24 Q Now, there then 219 1 apparently was another -- or this meeting was with 2 consultants on suicide in Europe, correct? 3 A Well, at least it was 4 European psychiatrists who were being used as 5 consultants, but is it clear that it was suicides 6 in Europe or was it suicides in general or 7 suicidality in general. It says to discuss 8 fluoxetine US clinical trials suicidality data, 9 maybe I misunderstood you, but I thought you were 10 saying it was European suicidality and it would 11 appear in that first paragraph to be US 12 suicidality data. 13 Q The fourth paragraph of 14 that document indicates that in connection with 15 the clinical trials that the clinical trial data 16 is limited, particularly the analysis of the 17 Hamilton Psychiatric Rating Scale for Depression, 18 Item 3, Suicidality, correct? 19 A Yes. 20 Q The next to the last 21 paragraph of that document indicates that, quote, 22 each of the consultants felt that the most 23 definitive assessment of a potential relationship 24 between fluoxetine treatment and suicidal ideation 220 1 or behavior would be some sort of prospective 2 study, correct? 3 A Yes. 4 Q And again that 5 prospective study was not done, was it, Doctor 6 Perelman? 7 A That's correct, yes, for 8 the reasons which I explained earlier. 9 Q Did you have anything 10 personally to do with the investigation in 11 connection with the Joseph Wesbecker tragedy in 12 Louisville? 13 A Personally? 14 Q Yes. 15 A No. 16 Q You didn't sit in on any 17 meetings or committees that discussed Lilly's 18 handling of that particular matter? 19 A It was an item of 20 discussion in that Tuesday morning task force that 21 we referred to earlier. 22 Q All right, tell me what 23 you recall about what was done in connection with 24 the Wesbecker matter or what was discussed in that 221 1 meeting? 2 MR. FREEMAN: Just don't 3 give any advice that was given by either outside 4 lawyers or inside lawyers. 5 A All right. Well, we 6 followed the information as it developed as to the 7 media coverage. I think there was -- as I recall, 8 there was contact at some stage with the Coroner; 9 whether we initiated it or he initiated it, I 10 don't recall. We simply tried to investigate as 11 much in the way of the facts as we could. 12 (PERELMAN EXHIBIT NO. 20 MARKED FOR 13 IDENTIFICATION.) 14 Q (BY MR. SMITH) Were 15 there outside attorneys present at these committee 16 meetings that were had in connection with the 17 Wesbecker matter as well as in-house lawyers? 18 A I don't recall that there 19 were or whether there were not. 20 Q The reason I asked is 21 because of the caution that Mr. Freeman gave you 22 with respect to not revealing any discussions by 23 outside or in-house counsel. 24 A Uh-huh. 222 1 Q And that raised my 2 question do you recall outside counsel being 3 there? 4 A I would say that there 5 were occasions when that Tuesday morning task 6 force met in which outside counsel were present. 7 I can't specify as to -- since we covered so much 8 subject matter over such a long period of time, 9 whether that was specifically the case with regard 10 to Wesbecker. 11 Q An individual by the name 12 of Ed Stopher is responsible for representing 13 Lilly in that litigation at this time. Does that 14 name ring a bell and does that help you in whether 15 or not Mr. Stopher was there? 16 A The name Ed Stopher does 17 not ring a bell with me. 18 Q Ed Stopher's name doesn't 19 mean anything to you either? 20 A No, regardless even of 21 whether he was present in a meeting or not 22 present, it doesn't ring a bell. 23 Q I'm sorry, I interrupted 24 you in reading Exhibit 20. 223 1 A No problem. In view of 2 the length and highly technical nature and the 3 fact that so many of these are references to 4 sections of a document not available here, I won't 5 read each line and will wait to see if I need to 6 as you ask questions of me to do that. 7 Q I don't blame you, Doctor 8 Perelman. Exhibit 20 is a Review of Fluoxetine 9 Safety Update and I got it from what was provided 10 to us from your file. 11 A From my file, all right. 12 Q And do you know whether 13 or not this Review of Fluoxetine Safety Update is 14 the same safety update that's mentioned in Exhibit 15 19 -- no, that's Fluoxetine Safety Experience 16 Summary, so it's probably two different documents. 17 A I would think it was two 18 different things. 19 Q Whatever, do you know 20 Marlene L. Cohen, Ph.D.? 21 A I do, well. 22 Q Who is Doctor Cohen? 23 A She works in the basic 24 research, discovery research area, a very 224 1 excellent scientist, came to us from the National 2 Institutes of Health many years ago, and is 3 considered a very excellent, outstanding 4 scientist, very critical scientist. 5 Q Is she with Eli Lilly and 6 Company? 7 A Yes, I'm sorry, I didn't 8 state that. 9 Q What is her present job 10 title, sir, if you know? 11 A Let's see, I think she 12 was promoted the last time around to research 13 advisor, which would be the technical ladder 14 equivalent of a director on the management ladder, 15 if you see what I mean. 16 Q I believe Doctor Ray 17 Fuller is a research advisor? 18 A No, he's moved up a 19 couple of steps from that; he was an advisor. 20 Q All right. 21 A I believe he's a fellow 22 now. 23 Q That's right. But you 24 respect Doctor Cohen's opinions very highly? 225 1 A Absolutely. 2 Q An excellent scientist 3 you said? 4 A Outstanding. 5 Q Turn to Point 8, would 6 you? 7 A To 1, 8? 8 Q Point 8 on Page 2. 9 A All right. 10 Q Doctor Cohen there 11 apparently makes the observation in connection 12 with her review of this safety update, "CNS 13 stimulation, agitation and insomnia. From the 14 data taken in concert, it might appear that there 15 is a somewhat greater incidence of CNS stimulation 16 with fluoxetine as compared to placebo. For 17 example, a great instance of insomnia and anxiety 18 was reported, (9-95, 9-113 and 9-370) agitation 19 seems pronounced (9-160) and a decrease in REM 20 sleep was reported, and there may be a suggestion 21 of manic psychosis," correct? 22 A That's the way it reads, 23 yes. 24 Q It says, "As with other 226 1 antidepressant agents used in the depressed 2 population, mania or CNS stimulation may be a 3 minor component to the actions of fluoxetine," 4 correct? 5 A Yes. 6 Q Do you recall seeing this 7 and reading this? 8 A I don't, no. 9 Q Do you have any idea when 10 this would have been prepared, Doctor Perelman? 11 A No, surprisingly it's 12 undated and I cannot -- no, sir. 13 Q Did you ever discuss with 14 Doctor Cohen in any respects her review of the 15 safety update which to her appeared that there is 16 a greater incidence of CNS stimulation with 17 fluoxetine, that there is a greater incidence of 18 insomnia and anxiety, and that agitation seemed 19 pronounced? 20 A I don't remember 21 receiving this and I don't remember any 22 discussions with her. 23 Q Do you remember any 24 discussions with Doctor Cohen at all in connection 227 1 with Prozac? 2 A No, sir, that's not her 3 normal area of operations. 4 Q That was going to be 5 exactly my next question. What normally does she 6 do? 7 A She has done research 8 more in the cardiac and receptor area, but not the 9 central nervous system. 10 Q Would it be safe to 11 assume that by virtue of your earlier expression 12 of your confidence in her ability as a scientist 13 and by virtue of the fact that she's reviewing a 14 safety update, that she might have been brought in 15 to give an independent analysis of the Prozac 16 safety update? 17 A That would mirror my 18 assumption exactly. 19 Q In other words, take 20 somebody that's not intimately associated with the 21 product and have them take a look at the data, 22 correct? 23 A Yes, sir. 24 Q There was a plan in 228 1 connection with Prozac to initially, in the 2 marketing of Prozac, focus on psychiatrists, 3 correct? 4 A Yes, sir. 5 Q And then there was a plan 6 from the outset to promote this drug for general 7 practitioner use? 8 A Yes. 9 Q This was never intended 10 by Lilly, as far as you're concerned, to be a 11 product that would be limited to psychiatrists to 12 dispense to the public? 13 A That's my understanding 14 and recollection, yes. 15 Q And that you knew and 16 planned from the time that Prozac was approved for 17 consumption in the United States in December 1987 18 that it would be prescribed by general 19 practitioners? 20 A Yes. 21 Q In fact, you wanted it to 22 be prescribed by general practitioners, did you 23 not? 24 A Yes. 229 1 Q Because obviously general 2 practitioners, there are more of them, correct, 3 than psychiatrists? 4 A Well, and they see many 5 depressed patients who don't ever make it to the 6 psychiatrist's office. 7 Q Yes. It's going to be of 8 benefit to the public generally by virtue of using 9 general practitioners, will it not? 10 A Yes. 11 Q And obviously will result 12 in increased sales for Lilly by virtue of the fact 13 that you have a greater number of physicians 14 prescribing the product? 15 A Yes. 16 (PERELMAN EXHIBIT NO. 21 MARKED FOR 17 IDENTIFICATION.) 18 Q (BY MR. SMITH) Exhibit 19 21 apparently is another of Doctor Thompson's 20 memos that was directed to Doctor Zerbe with a 21 copy to you? 22 A Yes. 23 Q It has to do with making 24 a retrospective examination in older studies of 230 1 fluoxetine the marginal notes made by 2 investigators, correct? 3 A Yes. 4 Q In the last sentence of 5 Paragraph 3 he says, "The HAM-D-3 scores 6 themselves are a valid and complete record of 7 suicidal thinking which required a positive 8 response from the investigators on each visit," 9 correct? 10 A Yes. 11 Q Have you determined, 12 Doctor Perelman, whether or not that sentence is 13 accurate? 14 A No, I have not. 15 Q It would appear by 16 looking at this other exhibit that Doctor 17 Heiligenstein disagrees with him when he says that 18 the clinical trials were not meant to assess 19 suicidal thinking, correct? 20 A Yes. 21 Q Doctor Thompson also 22 indicates in the last sentence of his memo under 23 Paragraph 4, "It is particularly important not to 24 comingle data, neither combining objective data 231 1 such as HAM-D-3 scores with comments or combining 2 comments made under one set of rules with marginal 3 notes made in a previous era." 4 A Yes. 5 Q Correct? 6 A Yes. 7 Q Do you know what he's 8 referring to in that connection? 9 A Yes, I was made aware of 10 the disagreement as to how to proceed in the 11 review of forms and kept abreast of developments 12 as the give and take, pro and con, proceeded 13 through several -- I believe several sessions. 14 Q What was the 15 disagreement, what were the pros and cons and how 16 did it come out? 17 A This was part of a 18 multiple recombing of the database to try to find 19 results that heretofore were not discernible in 20 the mass of data as analyzed previously, and one 21 suggestion was that it was called to our attention 22 that occasionally investigators, in addition to 23 filling the form out, would write marginal notes, 24 and there were those who felt that there would be 232 1 value to go back yet again to those original case 2 report forms and comb through the marginal notes 3 and make an assessment. It was Leigh's feeling, 4 and it may have been shared by others, I don't 5 know, but Leigh was the main proponent for the 6 view that that could lead to garbage in, garbage 7 out and utter confusion, because on the one hand 8 you have the HAM-D score which is quantitative and 9 as precise as psychiatric things can be, and on 10 the other hand you had the sort of ad-lib 11 spontaneous marginal notes and who knew what the 12 psychiatrist meant in each case and what the 13 observation was, and comingling that qualitative 14 sort of data with the quantitative data, would it 15 improve or corrupt the database. 16 And then I believe that 17 in later case report forms there was a space for 18 such notes, so that's yet a third form of 19 reporting, and Leigh was concerned about it making 20 it more foggy rather than less if we started 21 comingling that information. 22 Q How was it resolved? 23 A My recollection was after 24 a number of energetic discussions, none of which I 233 1 was present at but would hear about afterwards, my 2 recollection is that the prevailing view was that 3 regardless of the frailties that Leigh correctly 4 pointed out, that the screening and procedure 5 marginalia should go forward, and I believe it 6 did. 7 Q That's because the 8 marginal notes could have something very relevant 9 in connection with the issue on Prozac and 10 suicide? 11 A That was the supposition 12 under which it was decided to go forward, yes. 13 Q But Doctor Thompson had 14 concern about what you would do to your data when 15 you got all that stuff together? 16 A That's correct. 17 Q I take it from the fact 18 that you said there were some vigorous 19 discussions, you didn't have to end up solving the 20 problem? 21 A No. That almost never 22 happens, that senior-most management has to get 23 involved, they usually resolve it. 24 Q When you characterize 234 1 these discussions as vigorous that would be 2 reported to you later on, how would they be 3 reported to you later on? 4 A Portraying some of the 5 vigor. 6 Q The vigor of Doctor 7 Thompson? 8 A Well, the other side got 9 uncharacteristically energetic as well in their 10 point of view. 11 Q Who was the other side? 12 A As I recall, Doctor Zerbe 13 was one of a few, and I'm not sure which of the 14 psychiatrists, you probably will or already have 15 determined that from your other depositions, but 16 one or more of the other psychiatrists under 17 Doctor Zerbe as well. 18 (PERELMAN EXHIBIT NO. 22 MARKED FOR 19 IDENTIFICATION.) 20 Q (BY MR. SMITH) Exhibit 21 22 is a memo dated August 12, 1991 authored by 22 Gary D. Tollefson, correct? 23 A Yes. 24 Q Doctor Tollefson is a 235 1 psychiatrist? 2 A Yes. 3 Q Do you recall seeing this 4 memo? 5 A Yes. 6 Q All right. It's 7 concerning Prozac and suicidality and this paper 8 that Doctor Beasley is authoring, correct? 9 A Yes. 10 Q He said he "had the 11 opportunity to review the proposed resubmission to 12 the BMJ (August 9th version) this weekend. To be 13 candid I was disappointed, not in the efforts put 14 forth, but the process and end product," correct? 15 A Yes. 16 Q Now, did you have any 17 discussions with any of the individuals listed 18 here in connection with this memo? 19 A After reading the memo, I 20 asked a couple of different folks for background 21 as to what is going on here, yes. 22 Q All right. You felt that 23 this was something brewing that you needed to get 24 involved in? 236 1 A At least to be aware of 2 so that if it was necessary to get involved, I 3 would have some background. 4 Q Tell me who you talked to 5 or what background you got. 6 A Other than Bob Zerbe, I'm 7 not sure. I think that I talked with one or two 8 of the psychiatrists as well, but I don't know 9 which ones. 10 Q All right. Tell me about 11 your discussions with Doctor Zerbe. 12 A Well, knowing Gary as I 13 do, and the fact that I don't know how long he 14 would have been at the company at this time, I 15 think Bob Zerbe related what I had supposed, that 16 some of this was Gary's newness to the company, 17 coming from a more academic setting, and I don't 18 imagine Gary would express himself quite this way 19 today after being with the company for a bit, and 20 it was an explanation of how Gary felt, as it says 21 here, left out and aggrieved, wasn't aware of all 22 of the circumstances and pressures to get the 23 publication out, get it published preferably in 24 the BMJ, and sooner rather than later, and 237 1 consequently it was necessary to press ahead 2 whether he had an opportunity to get reinvolved or 3 not. 4 Q Doctor Tollefson wasn't a 5 author on the paper, was he? 6 A No. 7 Q What business was it of 8 Doctor Tollefson? 9 A Well, he was -- I believe 10 I'm correct, at this time he was executive 11 director of the central nervous system research 12 group, and this was -- the psychiatrists, I 13 believe, at this time, were reporting to him. 14 Q Okay. Would he have been 15 senior to, say, Doctor Zerbe? 16 A No, he reported to Doctor 17 Zerbe, who was a Vice President, and he is and was 18 an Executive Director. 19 Q So then would he have 20 been senior to Doctor Beasley, Doctor 21 Heiligenstein, Doctor Masica? 22 A Doctor Masica is a 23 director of level equivalent, so he would have 24 been senior to Doctor Masica, yes. 238 1 Q Did you talk to Doctor 2 Tollefson about this? 3 A I don't recall -- no, I 4 don't recall that I did. 5 Q Did Doctor Zerbe explain 6 to you what Doctor Tollefson meant that he was 7 disappointed in the process and in end product? 8 A Yes. 9 Q All right, what did he 10 say? 11 A Well, replaying it now a 12 couple of years later, all I can recall is that 13 with regard to the process, that having had an 14 opportunity to be involved previously, that when 15 he basically signed off with it and was happy with 16 it, there were some suggestions, that it was as 17 extensively revised as it was and there wasn't -- 18 I think he even references the courtesy in here of 19 coming back to him before going forward, so I 20 believe that's the process part of it, and he 21 didn't feel that the end product was of the 22 quality of what the previous draft was. 23 Q Well, he says, "What I 24 now see is a significant departure in the 239 1 conclusions on the redraft," doesn't he? 2 A Yes. 3 Q Does that mean that there 4 was some disagreement among the psychiatrists who 5 had been working on the paper in connection with 6 what the scientific significance of the data was? 7 A No, it related more as I 8 recall to what statistical methodology one uses, 9 but it did not change the ultimate outcome in 10 terms of what the conclusions are. I believe it 11 was considerable relationship to whether one uses 12 the two tail or chi-square, and I'm using words in 13 statistical knowledge I don't really understand, 14 but it was more of debates along that line. 15 Q Well, it says, "But more 16 importantly this draws attention to the process." 17 A Yes. 18 Q And by process, is he 19 meaning the fact that it wasn't rerun by him? 20 A I'm inferring, and I 21 think really you would need to ask that question 22 of Doctor Tollefson to have a clear answer. 23 Q We will, but as far as 24 your understanding was, that's what was reported 240 1 to you as being a complaint of Doctor Tollefson? 2 A Yes, that's correct. 3 Q And background material 4 is all you had to get, you didn't have to speak 5 directly to Doctor Tollefson or solve some bruised 6 egos? 7 A No. 8 MR. SMITH: Do you want 9 to stop here? 10 MR. FREEMAN: It's up to 11 you. 12 MR. SMITH: I thought you 13 wanted to stop at 4:30. 14 MR. FREEMAN: We did, but 15 I told you we'd go to 5:00 if you needed to. 16 MR. SMITH: I didn't hear 17 that. 18 MR. FREEMAN: Yes. 19 (PERELMAN EXHIBIT NO. 23 MARKED FOR 20 IDENTIFICATION.) 21 Q (BY MR. SMITH) Have you 22 seen Exhibit 23 before, Doctor Perelman? 23 A No. I'm puzzled as to 24 how we or you or anybody got a hold of what 241 1 appears to be an internal FDA memo, if I'm reading 2 it correct. 3 Q You say how did we get 4 it? 5 A (WITNESS MOVES HEAD UP 6 AND DOWN.) 7 Q It was supplied to us by 8 Lilly, I can tell because that stamp across it, 9 Fentress. 10 A No, I've never seen it 11 before. 12 Q But I think we got one, 13 too, through a FOIA, Freedom of Information Act 14 request. 15 A I see, okay. 16 Q Apparently, Doctor Zerbe 17 has instituted a call to Doctor Leber in 18 connection with an unfavorable study in connection 19 with Prozac, right? 20 A That would appear to be 21 the case, although I don't recall whether it truly 22 was a study as opposed to a gathering of a number 23 of cases, but be that as it may. 24 Q In any event, there was 242 1 some comparison of Prozac and maprotiline where 2 seven people on Prozac and no people on 3 maprotiline out of sixty on each attempted 4 suicide, correct? 5 A Yes. 6 Q It says there, "Potential 7 for a negative spin is obvious," correct? 8 A Uh-huh. 9 Q Is that a yes? 10 A Yes, sorry. 11 Q Did you discuss this 12 situation with Doctor Zerbe? 13 A I was aware, I was made 14 aware at some stage of the proposed Taiwanese 15 publication, yes. I can't specify that Doctor 16 Zerbe was the source. 17 Q Did you see that study or 18 the publication of that study as having a negative 19 spin? 20 A I saw that if and when 21 published, it would not be beneficial to the image 22 of Prozac. I don't know about -- the negative 23 spin I would stay away from since it's not my 24 choosing of words. 243 1 Q I'm just wondering 2 whether the term negative spin is Doctor Zerbe's 3 words or Doctor Leber's words. 4 A I have no way of knowing. 5 Q We're going to ask, 6 hopefully, each one of them that, but I just 7 wondered if you had had any conversations with 8 Doctor Zerbe where you had used the term negative 9 spin or whether he had used it. 10 A As I read the memo, it 11 would suggest to me that it is an FDA expression, 12 not a Zerbe, but I do not know. 13 Q Apparently there's an 14 Item 3, something marked out by virtue of the 15 space that is eliminated before, it says, "Zerbe 16 tries to get the poop, I say there's time enough 17 to get the details at the meeting." 18 A Uh-huh. 19 Q Is that yes? 20 A Yes, sorry, I see -- I'm 21 tracking what you've just read. 22 Q Does it appear to you 23 that there's something deleted from that? 24 A All I can say is there's 244 1 a blank space there. 2 Q And it's a long way to 3 carry a new paragraph marker, isn't it? 4 A Agreed. 5 Q This is dated March 13, 6 1992. Do you know whether you knew about the 7 Taiwanese study before Doctor Zerbe called Doctor 8 Leber? 9 A I do not. 10 Q What did you do in 11 connection with whether or not that study would be 12 published? When I say you, I'm using the 13 impersonal you as well the individual you. 14 A Yes. As I recall, this 15 was discussed in our Tuesday morning session at 16 least once, maybe more, and it was concluded that 17 we should get in touch with the Taiwanese 18 investigators and share with them our misgivings 19 about the quality of the study and the analyses 20 and the conclusions so they would have the benefit 21 of those concerns. 22 Q Did you, in fact, bring 23 them to Indianapolis to talk to them about it? 24 A I recall, I believe 245 1 Doctor Weinstein stopping in Taiwan on one of his 2 Asian trips soon after. I don't recall the 3 Taiwanese coming to Indianapolis. 4 Q We deposed Doctor Wong. 5 A David Wong? 6 Q Yes. 7 A Yes. 8 Q And he indicated that the 9 authors were here in Indianapolis. 10 A All right. 11 Q And that he had hosted 12 them in a dinner at his home. 13 A All right, well, then I 14 accept that if that's what David said in his 15 deposition. 16 Q And that there were 17 discussions not only about the article that was to 18 be published, but that in fact there was a 19 suggestion that the Taiwanese authors do another 20 study. Were you aware of that? 21 A Yes. 22 Q And that this study would 23 also involve Prozac? 24 A Yes. 246 1 Q And that by virtue of 2 them doing this study, they wouldn't publish the 3 results of their previous study? 4 A I don't know that I 5 recall that that was sort of a package arrangement 6 or anything of that sort. 7 (PERELMAN EXHIBIT NO. 24 MARKED FOR 8 IDENTIFICATION.) 9 Q (BY MR. SMITH) You 10 received Exhibit 24, did you not? 11 A Yes, I recall seeing 12 this, I believe. 13 Q And that is authored by 14 Doctor Allan Weinstein? 15 A That's correct. 16 Q And he was primarily 17 responsible for this Taiwanese situation, was he 18 not? 19 A For the Taiwan 86? 20 Q For the Taiwanese 21 situation. 22 A Situation, yes. 23 Q And he writes, Prozac, 24 Taiwan, mission successful. Professor Lu will not 247 1 present or publish his fluoxetine versus 2 maprotiline suicidality data. We will work with 3 him, in the very near future, to design a 4 prospective, randomized, controlled, double-blind 5 study of fluoxetine versus maprotiline, correct? 6 A Yes. 7 Q So it appears to me that 8 instead of publishing their data or writing an 9 article concerning the study that was not 10 favorable or had a negative spin in connection 11 with Prozac, they agreed to do another study? 12 A Yes. 13 Q That would be funded by 14 Lilly? 15 A Yes, that's my 16 recollection, we would fund it, yes. 17 Q And was that done? 18 A I don't recall if the 19 study -- if it was done, I don't recall that it 20 was. 21 Q Do you remember how much 22 money was budgeted for that study? 23 A No, sir. 24 Q Would there have been a 248 1 budget provided for that study? 2 A Since it was not -- I 3 mean, the budgets are prepared for the year in 4 advance when the profit plans were put together, 5 so when something like this would arise during the 6 year, there wouldn't be a budget item. 7 Q Well, there would have to 8 be some authorization to expend money for a study 9 such as this, would there not? 10 A But not being foreseen, 11 all I'm saying is there would not be a line item 12 in the budget, and, yes, money would have to be 13 provided, but whether there was any discussion of 14 what would be an appropriate sum in advance or 15 whether that would be devised afterwards, I don't 16 know, I don't recall. 17 Q How would that money be 18 obtained, would that be taken out of DISTAS or 19 Marketing's R and D budget? 20 A It would probably be 21 funded by the medical component clinical trial 22 budget within Lilly Research Laboratories rather 23 than by Marketing. 24 Q And Lilly Research Labs 249 1 had funds available to begin studies without 2 having to actually budget in advance, is that 3 correct? 4 A Yes. 5 Q Or in advance there had 6 been set aside funds for studies such as this? 7 A This would be a 8 relatively inexpensive study in a very large 9 budget, so there would be room to cover it. 10 Q Do you have any idea how 11 much a study like this would cost? 12 A I would be wildly 13 guessing or speculating. 14 Q I guess it would depend 15 on the number of patients? 16 A Absolutely. 17 Q The number of 18 investigators? 19 A Yes. On the other hand, 20 Taiwanese costs would be significantly less per 21 capita as well, so it's a guess. 22 MR. SMITH: I'm going to 23 let you go to the Pacers game, Doctor Perelman. 24 (WITNESS EXCUSED.) 250 1 *-*-*-*-* 2 STATE OF KENTUCKY ) ) SS. 3 COUNTY OF JEFFERSON ) 4 I, MARY KATHLEEN NOLD, a Notary Public within 5 and for the State at Large aforesaid, do hereby 6 certify that the foregoing is a true, correct and 7 complete transcript of the deposition of MELVIN 8 PERELMAN, PH.D., taken at the time and place and 9 for the purpose set out in the caption hereof; 10 that the witness was duly sworn before giving said 11 deposition; that the said deposition was taken 12 down by me in stenotype and afterwards transcribed 13 on a computer under my direction; that the 14 appearances were as set out in the caption hereof; 15 and that a request was made by counsel that the 16 deposition be submitted to the witness for reading 17 and signature. 18 GIVEN my hand as notary aforesaid, this 19 __________day of ___________________, 1994. 20 My commission expires March 10, 1996. 21 22 ________________________________ MARY KATHLEEN NOLD 23 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE 24 251 1 STATE OF___________________) ) SS: 2 COUNTY OF__________________) 3 I, MELVIN PERELMAN, PH.D., do hereby certify 4 that I have read the foregoing deposition given by 5 me on May 19, 1994, and that the answers contained 6 therein are true and correct to the best of my 7 knowledge and belief. 8 9 10 ______________________________ MELVIN PERELMAN, PH.D. 11 12 13 ______________________________ (DATE) 14 15 16 Subscribed and sworn to before me this day by 17 MELVIN PERELMAN, PH.D.. 18 My commission expires______________________. 19 20 ___________________________________ 21 NOTARY PUBLIC 22 23 ______________________________ 24 252 1 STATE OF____________________) ) SS: 2 COUNTY OF___________________) 3 I, MELVIN PERELMAN, PH.D., do here certify that 4 I have read the foregoing deposition given by me 5 on May 19, 1994, and that the answers contained 6 therein are true and correct to the best of my 7 knowledge and belief, with the following 8 corrections: 9 PAGE/LINE CORRECTION REASON FOR CORRECTION 10 __________________________________________________ 11 __________________________________________________ 12 __________________________________________________ 13 __________________________________________________ 14 __________________________________________________ 15 _________________________________ MELVIN PERELMAN, PH.D. 16 _______________________________ (DATE) 17 18 19 Subscribed and sworn to before me this day by 20 MELVIN PERELMAN, PH.D.. 21 My commission expires_____________________. 22 ________________________________ NOTARY PUBLIC 23 24 ________________________________ 253