1 DEPOSITION OF: PAUL STARK, Ph.D. TAKEN: March 5, 1993 2 _____________________________________________________________ 3 IN THE DISTRICT COURT OF DALLAS COUNTY, TEXAS 4 14TH JUDICIAL DISTRICT 5 JACKIE BIFFLE, et al., ) 6 ) Plaintiffs, ) 7 ) vs. ) CASE NO. 91-02496-A 8 ) ELI LILLY & COMPANY, et al., ) 9 ) Defendants. ) 10 ________________________________) 11 _____________________________________________________________ 12 IN THE DISTRICT COURT OF DALLAS COUNTY, TEXAS 192ND JUDICIAL DISTRICT 13 RICHARD HAROLD CROSSETT, JR., ) 14 CHAD H. CROSSETT, AMY MICHELLE ) CROSSETT and KRISTEN ANN ) 15 CROSSETT, INDIVIDUALLY AND AS ) SURVIVORS OF AND ON BEHALF OF ) 16 THE ESTATE OF JOCQUETTA ANN ) CROSSETT, Deceased, ) 17 ) Plaintiffs, ) 18 vs. ) CASE NO. 92-14775-K ) 19 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, HCA HEALTH ) 20 SERVICES OF TEXAS, INC., d/b/a ) and/or a/k/a HCA WILLOW PARK ) 21 HOSPITAL, HCA PSYCHIATRIC ) COMPANY, A TENNESSEE ) 22 CORPORATION, HCA PSYCHIATRIC ) COMPANY, A DELAWARE CORPORATION,) 23 HEALTH SERVICES ACQUISITION ) CORPORATION, A DELAWARE ) 24 CORPORATION, JAMES K. WITSCHY, ) M.D., ) 25 _________________Defendants.____) 2 1 DEPOSITION OF: PAUL STARK, Ph.D. TAKEN: March 5, 1993 2 _____________________________________________________________ 3 IN THE DISTRICT COURT OF ORANGE COUNTY, TEXAS 4 128TH JUDICIAL DISTRICT 5 MARIA GUADALUPE REVES, ) 6 INDIVIDUALLY AND AS NEXT FRIEND ) OF GRANT JULIAN REVES, A MINOR ) 7 CHILD, AND ON BEHALF OF THE ) ESTATE OF CHRISTIAN MARIE REVES,) 8 DECEASED, ) ) 9 Plaintiffs, ) vs. ) CASE NO. A-921,405-C 10 ) ELI LILLY & COMPANY, DISTA ) 11 PRODUCTS COMPANY, RAVIKUMAR ) KANNEGANTI, M.D., HOSPITAL ) 12 CORPORATION OF AMERICA, A ) TENNESSEE CORPORATION, HEALTH ) 13 SERVICES ACQUISITION CORP., ) A DELAWARE CORPORATION, HCA ) 14 PSYCHIATRIC COMPANY, A DELAWARE ) CORPORATION, TEXAS PSYCHIATRIC ) 15 CO., INC., a/k/a and/or d/b/a ) HCA BEAUMONT NEUROLOGICAL ) 16 HOSPITAL, AND HCA HEALTH ) SERVICES OF TEXAS , INC., a/k/a ) 17 and/or BEAUMONT NEUROLOGICAL ) HOSPITAL, ) 18 Defendants. ) ________________________________) 19 _____________________________________________________________ 20 IN THE UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF TEXAS 21 DALLAS DIVISION 22 DAYLYN PATTON, ) ) 23 Plaintiff, ) vs. ) CASE NO. 3-93-CV-0389-T 24 ELI LILLY & COMPANY, et al., ) ) 25 _________________Defendants.____) 3 1 DEPOSITION OF: PAUL STARK, Ph.D. TAKEN: March 5, 1993 2 _____________________________________________________________ 3 THE UNITED STATES DISTRICT COURT 4 FOR THE EASTERN DISTRICT OF TEXAS SHERMAN DIVISION 5 ANNETTE MARTIN, DARRELL WAYNE ) 6 MARTIN AND CHAD LANE MARTIN, ) INDIVIDUALLY AND AS SURVIVORS ) 7 AND STATUTORY BENEFICIARIES OF ) DENNIS WAYNE MARTIN, DECEASED, ) 8 ) Plaintiffs, ) 9 vs. ) CASE NO. 4:93 CV 43 ) 10 ELI LILLY & COMPANY AND DISTA ) PRODUCTS COMPANY, ) 11 Defendants. ) ________________________________) 12 _____________________________________________________________ 13 UNITED STATES DISTRICT COURT 14 SOUTHERN DISTRICT OF INDIANA INDIANAPOLIS DIVISION 15 16 IN RE: ELI LILLY AND COMPANY, ) Prozac Products ) 17 Liability Litigation ) MDL Docket No. 907 ________________________________) All Cases 18 19 VIDEOTAPED DEPOSITION OF: PAUL STARK, Ph.D. 20 DATE: March 5, 1993 21 _____________________________________________________________ 22 ASSOCIATED REPORTERS, INC. 23 2275 Main Street The Professional Center Post Office Box 1883 Suite 302 24 Fort Myers, FL 33902 201 W. Marion Avenue TELE: 813-332-0616 Punta Gorda, FL 33950 25 FAX: 813-332-4938 TELE: 813-637-0144 4 1 (Cont'g) 2 TIME: 9:23 a.m. to 4:20 p.m. 3 LOCATION: Sheraton Harbor Place Hotel 4 2500 Edwards Drive Fort Myers, Florida 5 TAKEN BY: Counsel for the Plaintiff Biffle 6 BEFORE: Debra L. Gunn, CP-RPR 7 Notary Public State of Florida at Large 8 9 10 * * * 11 12 APPEARANCES: 13 FOR THE PLAINTIFF BIFFLE: (Received original and one copy of transcript) 14 PAUL L. SMITH, ESQUIRE 15 PAUL L. SMITH AND ASSOCIATES, P.C. 745 Campbell Centre II, LB 48 16 8150 N. Central Expressway Dallas, Texas 75206 17 18 FOR THE PLAINTIFF WESTOVER (Received one copy of transcript) 19 GEORGE W. MURGATROYD, III, ESQUIRE 20 KANANACK, MURGATROYD & BAUM 12100 Wilshire Boulevard, Suite 650 21 Los Angeles, California 90025 22 23 24 25 5 1 APPEARANCES: (Cont'g) 2 FOR THE DEFENDANT ELI LILLY & COMPANY: (Received one copy of transcript) 3 JOE C. FREEMAN, JR., ESQUIRE 4 FREEMAN & HAWKINS 2 Peachtree Street 5 Atlanta, Georgia 30383 6 and 7 MARGARET M. HUFF, ESQUIRE ELI LILLY & COMPANY 8 Lilly Corporate Center Indianapolis, Indiana 46285 9 and 10 WADE C. SMITH, ESQUIRE 11 TOUCHSTONE, BERNAYS, JOHNSTON, BEALL & SMITH, L.L.P. 12 4700 Renaissance Tower 1201 Elm Street 13 Dallas, Texas 75270-2196 14 and 15 JOHN F. BRENNER, ESQUIRE McCARTER & ENGLISH 16 Four Gateway Center 100 Mulberry Street 17 Newark, New Jersey 07102-4096 18 FOR THE DEFENDANT BEAUMONT NEUROLOGICAL HOSPITAL: 19 (Received one copy of transcript) 20 GAIL FRIEND, ESQUIRE BARTLETT & FRIEND 21 1303 McKinney, Suite 2900 Houston, Texas 77010 22 23 ALSO PRESENT: 24 Jaren Whitmore, Paralegal Carl Sobeck, Cape Coral Videography 25 6 1 2 I N D E X 3 ATTORNEY____________DIRECT____CROSS_____REDIRECT_____RECROSS 4 Mr. Paul Smith 10 5 _____________________________________________________________ 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 7 1 Thereupon, 2 PAUL STARK, Ph.D., 3 a witness, produced for and in behalf of the Plaintiff 4 Biffle, having been first duly sworn, deposes and says as 5 follows: 6 THE REPORTER: Good afternoon. 7 My name is Debra Gunn; I'm here from the offices 8 of Associated Reporters, Inc., located at 2275 Main 9 Street, Fort Myers, Florida. 10 We're here at the Sheraton Harbor Place Hotel 11 located at 2500 Edwards Drive, Fort Myers, Florida to 12 take the deposition of Dr. Paul Stark. Today's date is 13 March 5, 1993; the time is now 9:23 a.m. 14 Also present is Carl Sobeck from Cape Coral 15 Videography. 16 If counsel will please identify themselves for the 17 record. 18 MR. PAUL SMITH: My name is Paul Smith; I'm here 19 as attorney for the plaintiff in the Biffle case. 20 MR. FREEMAN: My name is Joe Freeman; I'm here for 21 Eli Lilly & Company. 22 MR. WADE SMITH: My name is Wade Smith, I'm here 23 for Eli Lilly & Company. 24 MS. FRIEND: My name is Gail Friend; I'm here for 25 Beaumont Neurological Hospital in the Reves case, 8 1 R-E-V-E-S. 2 THE REPORTER: Sir, if I can ask you to raise your 3 right hand to be sworn, please. 4 MR. FREEMAN: Let me say for the record that I 5 think we should make objections only as to the form of 6 the question and the responsiveness of the answer, and 7 reserve all other objections until time of trial or 8 hearing. 9 MR. PAUL SMITH: That's fine. 10 What do we want to do about signature and filing 11 of the deposition? 12 MR. FREEMAN: Why don't we stipulate that the 13 court reporter can send it to Dr. Stark at his home, 14 that he can sign it before any notary public and make 15 whatever corrections, if any, he has on an errata sheet 16 and get it back to the court reporter within thirty days 17 of receipt of it, otherwise, the signature will be 18 waived. 19 MR. PAUL SMITH: All right. And if a signed, 20 notarized copy is not received for some reason, an 21 unsigned copy can be used for purposes of hearing or 22 trials. 23 MR. FREEMAN: That's correct. 24 MS. FRIEND: For all purposes; for all purposes? 25 MR. PAUL SMITH: Yes. 9 1 MS. FRIEND: Okay. Is this under the Texas rules 2 where you have to have it within ten days? Are we 3 taking it under the Texas rules? 4 MR. PAUL SMITH: Well, we're waiving that ten-day 5 requirement and going into an agreement where Dr. Stark 6 can sign the --. 7 MS. FRIEND: The deposition, but until it's 8 signed, we can use it for all purposes until a signed 9 one is sent. 10 MR. PAUL SMITH: Right. 11 MR. FREEMAN: Since in the MDL proceeding we have 12 to designate what parts we deem to be confidential 13 within fifteen days, if you would please mail to me at 14 my office the original deposition as soon as you get it 15 transcribed, and I would ask for an expedited copy, so 16 that we can designate if there be any such sections that 17 we deem to be confidential. 18 MR. PAUL SMITH: Also, there will be another 19 individual here. George Murgatroyd will be here for the 20 MDL plaintiffs later this afternoon -- or later this 21 morning, but has asked that we go ahead and continue so 22 that we can get started. 23 24 25 10 1 DIRECT EXAMINATION 2 BY MR. PAUL SMITH: 3 Q. Would you state your name, please, sir. 4 A. Paul Stark. 5 Q. How old of a man are you, Dr. Stark? 6 A. I'm sixty-four years old. 7 Q. Where do you live? 8 A. My permanent address is XXXXXXXXXXXXXXXXXXXXXX. 9 Q. And what is that address in XXXXXXXXXXXXXXXXXXXXXX 10 that's your permanent address? 11 A. XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. 12 Q. What's that zip? 13 A. XXXXX. 14 Q. Is that a house? 15 A. It's a condominium, yes. 16 Q. Do you have any temporary residences, Dr. Stark? 17 A. Yes, I do. 18 Q. Where, please? 19 A. XXXXXXXXXXXXXXXXXX. 20 Q. And what is your address in XXXXXXXXXXXXXXX? 21 A. XXXXXXXXXXXXXXXXXXXXX. 22 Q. And the zip there. 23 A. XXXXX. 24 Q. Is XXXXXXXXXXXXXX a mailing address? 25 A. Yes. 11 1 Q. It doesn't have to go to XXXXXXXXXX? 2 A. No. You can just send it so XXXXXXX, as a matter 3 of fact; don't have to use the word XXXXXXXXXX 4 Q. How long have you maintained a temporary residence 5 in XXXXXXXXXXXXXXX? 6 A. XXXXXXXXXX. 7 Q. Is that a home or a condominium? 8 A. It's a home. 9 Q. How long have you maintained your residence in 10 XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX? 11 A. XXXXXXXXXXXXXXXX. 12 Q. Do you currently divide your time between your 13 XXXXXXXXXXXXXXXXXXXXXXXX addresses? 14 A. Yes, I do. 15 Q. Can you give me a general approximation of what 16 time you spend in XXXXXXXXXXXX and what time you spend in 17 XXXXXXX? 18 A. About eight months in XXXXXXXXXXXX and four months 19 on XXXXXXXX. 20 Q. You spend the winter months in XXXXXXXXX and the 21 summer months in XXXXXXXXXXXXX? 22 A. Correct. 23 Q. Or that's the intent, at least. 24 A. Yes. 25 Q. Do you have any other temporary residences or 12 1 condominiums anywhere else? 2 A. I have a condo that I stay at out in XXXXXXXXXX, 3 XXXXXXXXXXX when I'm out there on business. Our company 4 offices, home offices, are in San Diego. 5 Q. That's XXXXXXXXXX? 6 A. XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. 7 Q. Do you know the zip right off the top of your 8 head? 9 A. No, I don't. 10 MR. PAUL SMITH: Are you having problems? I 11 had -- I broke my mike and I had to change mikes. 12 THE WITNESS: Sounds like you're talking to 13 yourself because he refused to answer you. 14 BY MR. PAUL SMITH: 15 Q. How much time do you spend at the condo in 16 XXXXXXXXXXX? 17 A. For the most part when I make a business trip out 18 there, I spend usually about a week, and I probably go out 19 there six times a year. 20 Q. Is there any particular season or time that you go 21 to -- that's the San Diego area? 22 A. Yes. 23 Q. -- that you go to that area? 24 A. No. I go there on a regular basis to conduct our 25 business out there. Our home offices of our company are out 13 1 there. 2 Q. What is that company, sir? 3 A. International Clinical Research Corporation. 4 Q. And what is International Clinical Research 5 Corporation? 6 A. That's the name of our company. 7 Q. What is it? 8 A. I don't know what your question is. 9 Q. What type of company is it? 10 A. Oh, we are a CRO; that's a clinical research 11 organization, a contract organization. 12 Q. So you do research under independent separate 13 contracts for entities. 14 A. That is correct. 15 Q. Any other temporary residences that you might 16 maintain? 17 A. No. 18 Q. Are you married, Dr. Stark? 19 A. Yes, I am. 20 Q. Does your wife work outside the home? 21 A. No, she does not. 22 Q. Do you have children? 23 A. Yes, I do. 24 Q. And generally what are the ages of those children? 25 A. XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. 14 1 Q. So they are all grown and gone? 2 A. Yes, sir. 3 Q. Are any of your children in the medical or 4 scientific field? 5 A. Yes. 6 Q. Tell me which children of yours are in the medical 7 and scientific field. 8 A. XXXXXXXXXXXXXXXXXXXX 9 Q. What is her last name? 10 A. XXXXXX. 11 Q. And what is her occupation? 12 A. She is a supervisor with a CRO company. 13 Q. That International Clinical Research Corporation 14 that you mentioned earlier? 15 A. Yes. 16 Q. You say she is a supervisor? 17 A. Yes. 18 Q. I take it she's among a number of supervisors. 19 A. Yes. 20 Q. What is her educational background? 21 A. Bachelor's degree and a master's in social work. 22 Q. Was her bachelor's degree in social work also? 23 A. Why'd you ask me that? I don't recall. 24 Q. Does she live in the xxxxxxxxx area? 25 A. Yes, she does. 15 1 Q. Any other of your children who are in the medical 2 or scientific field -- 3 A. No. 4 Q. -- either by occupation or by training? 5 A. No. 6 Q. Is your wife trained or in the past had an 7 occupation in the scientific or medical field? 8 A. Not in the medical field. I don't know what you 9 would define as "scientific," however. 10 Q. Something having to do with research or 11 development of theories pertaining to science. 12 A. Yeah, sort of. 13 Q. All right. Tell me about her, either her 14 occupation or her educational background, that puts her in 15 the scientific field. 16 A. I think her background has to do with actually 17 arts, but -- arts. 18 Q. Hearts, like tickers? 19 A. Arts, A-R-T-S. 20 Q. Arts, okay 21 A. No, not tickers. But her road experience would be 22 in the computers, and she worked for Naval Avionics in 23 Indianapolis. 24 Q. But she's a computer-knowledgeable individual. 25 A. I believe so, especially with my ignorance. I'm 16 1 very impressed with her knowledge about them. 2 Q. Has she done any work for International Clinical 3 Research Corporation? 4 A. No, no. 5 Q. Let's talk about your educational background, Dr. 6 Stark. 7 You do have a Ph.D., do you not? 8 A. Yes, sir. 9 Q. And is it appropriate for me to call you Dr. 10 Stark; is that all right? 11 A. Yes. Actually I'm very complimented. You should 12 hear what some people call me. 13 Q. I understand. 14 Why don't you tell me about your educational 15 background, beginning with high school. 16 A. I attended Strathcona Academy in Montreal, Canada. 17 Q. Spell that for me, please. 18 A. S-T-R-A-T-H-C-O-N-A. All one word, by the way. 19 It's a famous Indian in Canada. 20 Q. And that's where you got your high school diploma? 21 A. Yes. 22 Q. All right. Then what education did you have 23 following that? 24 A. I attended McGill University. 25 Q. I'm sorry? 17 1 A. I attended McGill University in Montreal and 2 obtained a Bachelor of Science Degree in biochemistry. 3 Q. In what year? 4 A. 1949. 5 Q. And when did you graduate from high school? 6 A. 1945. 7 Q. Did you grow up in Montreal? 8 A. Yes, I was raised there until -- I stayed there 9 until I finished McGill. 10 Q. Were you born a Canadian citizen? 11 A. No; I was actually born an American citizen. My 12 parents were Canadian. 13 Q. But you were born in the United States. 14 A. Yes. 15 Q. Then after McGill University, what was your next 16 educational endeavor? 17 A. I got my Ph.D., University of Rochester School of 18 Medicine. 19 Q. All right. When? 20 A. 1963. 21 Q. Now, did you get a master's degree in between your 22 Bachelor of Science? 23 A. No; went straight through. 24 Q. You don't have to have a master's degree before 25 you can become a doctoral candidate to receive your Ph.D. 18 1 from the University of Rochester School of Medicine? 2 A. No, you don't. 3 Q. What was your Ph.D. in? 4 A. Pharmacology. 5 Q. Any other educational training? 6 A. Yes. I have a J.D. 7 Q. Juris doctorate? 8 A. Yes. 9 Q. All right. So you have a law degree. 10 A. Yes, I do. 11 Q. When and where did you get that law degree? 12 A. Graduated in 1977, Indiana University School of 13 Law. 14 Q. When did you start at the Indiana University 15 School of Law? 16 A. 1973. 17 Q. Were you a full-time law student when you were in 18 law school? 19 A. No. 20 Q. Were you going to a night class -- 21 A. Yes. 22 Q. -- or part-time curriculum? 23 A. I went night school and summer. 24 Q. Any other educational degrees or training that 25 you've had, Dr. Stark? 19 1 A. No. 2 Q. Did you say that McGill University is located in 3 Montreal? 4 A. Yes, sir. 5 Q. Were any of your degrees with honors? 6 A. Yes; my law school was. 7 Q. What's it say on the diploma? 8 A. Cum laude. I think that's good. 9 Q. It ain't on mine, Dr. Stark. 10 A. You're too kind is what you are. 11 Q. Did you concentrate on any particular area of law 12 while you were at the Indiana University School of Law? 13 A. No. 14 Q. Did you do a doctoral thesis when you got your 15 pharmacology Ph.D.? 16 A. Yes, I did. 17 Q. And what was that on? 18 A. Cholinergic mechanisms is the best I can describe 19 it to you, I guess. 20 Q. Basically what is that? 21 A. I established a punitive transmitter system that 22 affected behavior in animals. 23 Q. Did that have to do with neuropharmacology? 24 A. Yes. My training is in neuropsychopharmacology. 25 Q. Well, is there a branch or a specialty within 20 1 pharmacology that has to do with brain chemicals? 2 A. Sure. 3 Q. What would that specialty be called? 4 A. To the best of my knowledge, it's usually just 5 biochemical pharmacology. 6 Q. All right. Then you said you were a specialist in 7 neuropsychopharmacology; is that right? 8 A. That's what I was trained in, yes; let's put it 9 that way, yes. 10 Q. Tell me what that is. I mean, it sounds like an 11 even more specialized area than biochemical pharmacology; is 12 that correct? 13 A. I don't know that it's more specialized. 14 Q. Well, a different area of interest, at least. 15 A. Very briefly - I think it's the only way to answer 16 that question is briefly, unless, indeed, nobody is going to 17 catch their plane tonight - it's the study of how drugs 18 affect the mind or the central nervous system and behavior 19 and other neurological activity. 20 Q. And that's called neuropsychopharmacology? 21 A. Correct. 22 Q. I guess "neuro" having to do with the neurological 23 aspects of our body system; would that be right? 24 A. I would guess. 25 Q. Well, is that your impression? 21 1 A. That's my impression, yes. 2 Q. I mean, you're the neuropsychopharmacologist. I'm 3 asking you, am I correct that the "neuro" in that has to do 4 with the neurological system? 5 A. That central nervous system, yes. 6 Q. And "psycho" has to do with behavior or 7 psychiatry; is that correct? 8 A. That's correct. 9 Q. And "pharmacology" has to do with drugs. 10 A. That is correct. 11 Q. So what do you have to do to become a 12 neuropsychopharmacologist? 13 A. Work very, very hard. 14 Q. When did you first consider yourself a 15 neuropsychopharmacologist? 16 A. When I graduated. 17 Q. From --? 18 A. From the University of Rochester. 19 Q. All right. What courses did you study at the 20 University of Rochester that qualified you to become a 21 neuropsychopharmacologist? 22 A. To answer you in, I think, an accurate manner, I'd 23 have to say every course I took. 24 Q. All right. Well, were there some courses that 25 were designed specifically that examined the central nervous 22 1 system there in your education? 2 A. Of course, because all -- there were several 3 courses, many courses that go along those lines, and that are 4 not specific necessary for a neuropsychopharmacologist. 5 Q. Were there courses there that you took at the 6 University of Rochester that had to do with psychology? 7 A. No. I never thought of it. Thank you. 8 Q. Were there courses there that had to do with 9 pharmacological aspects of your curriculum? 10 A. Yes. 11 Q. Have you ever taken any courses in psychology? 12 A. No. 13 Q. And I'm not talking about at the -- exclusively at 14 the University of Rochester School of Medicine, I'm talking 15 about at McGill University or at -- say that academy again 16 for me. 17 A. Strathcona Academy. 18 Q. Strathcona Academy. 19 A. No. 20 Q. So you've not taken a psychology course in any of 21 those universities. 22 A. That's correct. 23 Q. Have you taken psychiatry courses in any of those 24 universities? 25 A. Nope. 23 1 Q. Did you take any psychology or psychiatry courses 2 at Indiana University School of Law? 3 A. No. I'm not trying to trick you, honest to God. 4 Q. Have we covered your educational background, Dr. 5 Stark? 6 A. Yes, you have. 7 Q. Let me ask you before we leave that area: Is 8 there any particular course or curriculum that you took on 9 your own or as an independent study for any purposes, any 10 purposes throughout your lifetime, and that might -- do you 11 understand what I'm asking you? 12 A. No. 13 Q. You know, it might be something from fine art 14 appreciation or music appreciation at some local junior 15 college, or it might be something like astronomy at some 16 other course, you know, something that maybe not was dealing 17 directly with your field of endeavor -- 18 A. Yes, I have; yes, I have. 19 Q. -- but something that gives you more than the 20 average education on a particular subject. 21 A. Yes, I have. 22 Q. Tell me about that, please. 23 A. Auto repair. 24 Q. Auto repair? 25 A. Uh-huh. 24 1 Q. Have you while you have been associated with any 2 of your employers taken any specific courses to specialize 3 you in a particular area having to do with your employment? 4 A. Let me broaden your answer for no good reason just 5 because I think it may save time, so I'll break my own rules. 6 Q. Okay. 7 A. I have attended meetings, symposia and so on 8 within my area of expertise on behalf of Eli Lilly & Company 9 where I was employed, okay. 10 Q. Were any of those meetings or symposia meetings or 11 studies that took over one week? 12 A. Nope. 13 Q. For instance, did Lilly, for example, sponsor you 14 as a fellow to maybe go off in Switzerland and study some 15 neuropsychopharmacological problem? 16 A. Unfortunately, no. 17 Q. All right. And when I say Switzerland, I'm 18 talking about, you know, where you go get a particular 19 individualized intense course of study in a particular area. 20 A. No. 21 Q. You know, medical doctors will sometimes go take a 22 sabbatical and study under a particular program for a while. 23 A. I did not. 24 MR. PAUL SMITH: Off the record a second. Let me 25 get a cup of coffee. 25 1 THE VIDEOGRAPHER: Off camera. 2 (Deposition recessed.) 3 (Deposition resumed.) 4 THE VIDEOGRAPHER: On camera. 5 BY MR. PAUL SMITH: 6 Q. I'd like to go over with you now, Dr. Stark, your 7 work history, and let's start with any employment that you 8 might have had while you were in undergraduate school. 9 Did you work as an undergraduate student? 10 A. Yes. 11 Q. Tell me about that. 12 A. To the best of my recollection, I was a waiter 13 in the summers, worked on a farm for five months, painted a 14 bridge coming onto the island of Montreal. 15 During the school year I worked in a coffee shop, 16 I was an instructor in the physics lab to earn extra money, 17 worked for the college grounds department; that covers my 18 undergraduate, I think. I'm not sure, I might have sold 19 shoes at the T. Eaton Company in Montreal, too, during 20 Christmas holidays. 21 Q. Was all of this employment in the Montreal or 22 Montreal area? 23 A. Yes. 24 Q. And was all of that employment part-time 25 employment? 26 1 A. Yes. Summertime, of course, was full time during 2 the summer when school was out, but it wasn't a permanent 3 job. 4 Q. But you didn't take a year off from McGill 5 University and work for some reason? 6 A. No, no. 7 Q. As an instructor in physics, did you do that 8 because you had a particular interest in physics? Did you 9 excel in physics? 10 A. No, sir. 11 Q. That's two questions. 12 A. No, I did not excel and I didn't have a particular 13 interest in physics. It was a job opening. 14 Q. And you could do it better than your potential 15 students. 16 A. I don't know. 17 Q. All right. After you got your Bachelor of Science 18 from McGill University in 1949, did you become employed? 19 A. Yes. 20 Q. What was your first job after you got your BS 21 degree? 22 A. I think it was with Sharp & Dohme before they 23 became Merck, Sharp & Dohme. 24 Q. Dohme is spelled D-O--. 25 A. D-O-H-M-E. Yes, from those who know, yes. 27 1 Q. You were in high school and college from 1945 to 2 1949. 3 Did you serve in the military at all? 4 A. No. I was an air cadet in high school, which 5 was -- I don't know how to describe it. When you were in 6 your junior and senior year, that was during the war, you 7 could either go into the Army, Navy or Air Force type of 8 paramilitary, and that's what I was in. 9 Q. But by the time you'd graduated from high school, 10 the war was over. 11 A. That's correct. 12 Q. And were they not drafting at that time? 13 A. No. 14 Q. And never drafted while you were of draft age? 15 A. Nope. 16 Q. What about Korea, did they -- did they examine you 17 for Korea? 18 A. Yeah, and they made me 4-F. 19 Q. Because of physical condition? 20 A. Yes, sir. 21 Q. What was that? 22 A. Well, you know, the only thing that came to my 23 mind was my mental condition; I'm sorry. 24 Q. I'll hit you with jabs like that ever so often, 25 Dr. Stark. You know, they'll come and you won't even see 28 1 them. 2 A. Actually it was very good, sir. 3 Q. What physical condition required that you be 4-F? 4 A. I had had a duodenal ulcer as a child. 5 Q. All right. Let's go back to Sharp & Dohme. 6 When did you begin with Sharp & Dohme? 7 A. In '49. 8 Q. And what was your position with Sharp & Dohme when 9 you began? 10 A. Pharmacologist. They gave me that title because I 11 was in the pharmacology department, if you had a bachelor's 12 degree; it wasn't because of any expertise at that particular 13 time in pharmacology. 14 Q. That was going to be my next question. You did 15 not become a technical or a recognized pharmacologist until 16 you received your Ph.D., did you? 17 A. Yes and no. 18 Q. All right. Can you explain that for me? 19 A. Yeah. I guess you might look at it as sort of an 20 apprenticeship. 21 Q. Well, you probably weren't any smarter the day 22 after you got your Ph.D. than the day before anyway, were 23 you? 24 A. Probably not. I did pharmacology actually with 25 a D.V.M., and as a consequence I started learning 29 1 pharmacological techniques and procedures and so on. 2 I wasn't looking to avoid your question, it's 3 just -- my answer was not a facetious one. I more or less 4 became one as I served my time. 5 Q. You said you began pharmacology with a D.V.M.? 6 A. I worked with a -- the person who was in there was 7 a D.V.M. 8 Q. A veterinarian? 9 A. Yes. 10 Q. At Sharp & Dohme? 11 A. Yes. 12 Q. We'll get into that. 13 You started with Sharp & Dohme in 1949 as a 14 pharmacologist; your title was pharmacologist there -- 15 A. Yes. 16 Q. -- by Sharp & Dohme? 17 A. Yes. 18 Q. And how long did you work for Sharp & Dohme? 19 A. I'm trying to remember, and I may not be 20 precise -- 21 Q. I won't hold you to the specifics at this time. 22 A. -- so I'll qualify that. I'm sorry. 23 Within about two years after I was there they had 24 set up for me to go to Western Reserve to get an M.D./Ph.D. 25 They had set up an eight-year scholarship for me, and I was 30 1 there for two years and had taken course work and I knew I 2 wasn't going to last six more years, and I packed up and came 3 back to Rochester, New York where my wife was from. 4 Q. All right, sir. You worked for Sharp & Dohme from 5 1949 until 1951? 6 A. About two years, yeah; about. 7 Q. During that period of time, what did you do for 8 them; what were your various positions? 9 A. Pharmacologist. 10 Q. All right. Did you ever become anything other 11 than the title "pharmacologist"? 12 A. Nope. 13 Q. Did they classify pharmacologist within the 14 company as, say, Pharmacologist One or Pharmacologist Two? 15 A. Not that I recall, but I don't recall is probably 16 even more accurate. 17 Q. What did you do as a pharmacologist for Sharp & 18 Dohme? 19 A. I was involved primarily in evaluating new 20 compounds in in vitro systems having to do with the 21 gastrointestinal area, primarily. 22 Q. In vitro means --? 23 A. Outside the body, in test tubes; but actually it 24 had to do with isolated systems, gastrointestinal ones, the 25 gut. 31 1 Q. I'm sorry? 2 A. The gut. 3 Q. And you were evaluating new compounds for 4 treatment of gastrointestinal disorders? 5 A. Correct. 6 Q. And what compounds were those? Did they ever 7 become something that was used? 8 A. I don't recall at all. 9 I moved from there into then helping Dr. McManus. 10 He's no longer alive, but I remember him well. 11 Q. Was he the D.V.M. that you worked with? 12 A. Yeah, yeah, yeah; and he would prepare the various 13 animal models, and I got to work with him on that. 14 Q. All right. Was Dr. McManus evaluating new 15 compounds in in vitro systems having to do with the 16 gastrointestinal areas? 17 A. Yeah. He was my boss in essence; he was my boss 18 in essence. 19 Q. And since he's the veterinarian, were you all 20 giving this compound to dogs and cats and animals? 21 A. As I recall, the animals that were used at that 22 time were dogs, is all I can recall. 23 Q. All right. Tell me specifically what your job 24 duties were in connection with this evaluation of new 25 compounds in in vitro systems having to do with the 32 1 gastrointestinal area. 2 A. The in vitro ones? 3 Q. Yeah. 4 A. We would -- I will try to recall. They used to 5 string up strips of the intestine that were gotten from 6 slaughterhouses and measure the effect on the contraction and 7 relaxation that would take place when you added these 8 experimental drugs to the solutions in which they were 9 immersed. 10 Q. Sounds fascinating. 11 A. No, it wasn't. We used to record them on a 12 kymograph. 13 Do you know what a kymograph is? 14 Q. No. 15 A. It's a smoked drum. We used to actually smoke 16 paper and used to -- this was -- I'm going back to many years 17 ago, as you know, and we used to record the contractions with 18 this little stylus writing on smoked paper, and they'd we'd 19 shellac it to preserve it. 20 It's a very pleasant memory I have that you just 21 drew forth from me. 22 Q. That was kind of a -- one of the more cruder 23 research techniques. 24 A. It was the early days of recording. 25 Q. Right. 33 1 Well, were you one of a team that was evaluating 2 these compounds? 3 A. In the gastrointestinal area, it was just the two 4 of us doing that. There were other groups, but I was not 5 familiar with them. 6 We were essentially in various -- at that time it 7 was a very small company. It was almost -- I was going to 8 say huts; they weren't really huts, it was like a cottage. 9 And we did our thing, then we'd get together for lunch. I 10 never really knew what the other guys were doing. 11 Q. Kind of separated and devoted yourself only to 12 that one particular area. 13 A. Yes. 14 Q. All right. When you moved with the veterinarian, 15 I assume you were going then ex vitro. 16 A. I went from in vitro to in vivo with him. 17 Q. I mean in vivo, okay. 18 And tell me what you did in connection with the 19 dogs; start giving this stuff to them? 20 A. Yes. I guess in answer to your question, yes. 21 Q. And were you conducting experiments? 22 A. Yes; yes. 23 Q. Tell me about the experiments that you would do. 24 A. In what way? 25 Q. Well, do you recall any of the experiments that 34 1 you ran in evaluating that compound? 2 A. I don't know what you're asking me, I guess. 3 Q. Maybe I'm not asking it well or maybe I don't know 4 how to ask it. 5 Would you take dogs, administer a compound to 6 them, and then measure some reaction that that dog might 7 have? 8 A. Yes, yes, yes, yes, yes, yes. 9 Q. All right. Tell me how you would -- give me an 10 example of the some of the type of measurements you would 11 make and things of that nature. 12 A. We'd measure the intestinal contraction, gastric 13 secretion. 14 Q. Did you evaluate while you were at Sharp & Dohme 15 any other new compounds other than the gastrointestinal 16 compounds? 17 A. No, I was never involved with anything else. 18 Q. And did you do that for two years? 19 A. Yeah. 20 Q. And did you work with anyone other than Dr. 21 McManus there? 22 A. I used to meet with the chemists and tell them 23 what we saw, what seemed to be structures that would lead to 24 better activity or lesser activity and so on. 25 Q. You would meet with the chemists who were -- what 35 1 were they doing, making alterations to compounds? 2 A. Yeah, sure. 3 Q. So you were trying to come up with some new 4 compound; is that right? 5 A. That is correct. 6 Q. You weren't testing a compound that had already 7 been selected for further clinical trials or things of that 8 nature -- 9 A. No. 10 Q. -- is that correct? 11 A. That's correct. 12 Q. This was pure research and development that you 13 were involved with at Sharp & Dohme. 14 A. Yes. 15 Q. You were trying to develop a new product for 16 Sharp & Dohme, and you were researching particular compounds 17 to see if you could come up with a new product; would that be 18 correct? 19 A. Well, I guess we were looking to see what the 20 activity of the new compounds were. 21 Q. But the compounds would change and be altered 22 to -- 23 A. Oh, yes. 24 Q. -- to analyze different effects. 25 A. Absolutely, absolutely. 36 1 Q. Whereas, there might be in other situations - and 2 probably later in your career - evaluating compounds that 3 were already set that there weren't going to be any changes 4 in the compound, you were just trying to test that compound 5 over a longer period of time; for instance, a clinical trial? 6 A. Yes, I think that's accurate, what you've 7 described. I was trying to think in terms of what I did in 8 later parts of my career. 9 Q. We're going to get to that, so maybe you could 10 identify it at that time. 11 But this was pure research and development at 12 Sharp & Dohme. 13 A. Yes. 14 Q. Now, tell me about this situation with Western 15 Reserve. Did you actually go to Western Reserve 16 University -- 17 A. Yes. 18 Q. -- and enroll in their M.D.A., Ph.D. program? 19 A. Yes, M.D., Ph.D. 20 Q. And when did you do that? 21 A. I'm picking, roughly, about two years after I 22 started at Sharp & Dohme I went there, and I was at Western 23 Reserve for two years. 24 Q. So in 1951 to 1953, approximately. 25 A. Yeah, approximately. 37 1 Q. Now, were you still a paid employee of 2 Sharp & Dohme during this period of time? 3 A. No, nope. 4 Q. I got the impression that this was something that 5 Sharp & Dohme wanted you to do or encouraged you to do. 6 A. They did. 7 Q. What did they do, give you a leave of absence 8 and --? 9 A. Yes. 10 Q. Did they pay your tuition? 11 A. No; actually it was paid for by the university. 12 I had a -- they gave me an eight-year scholarship, 13 in which all my tuition was paid. 14 It so happened that the person who was head of 15 pharmacology used to be a former Sharp & Dohme employee, and 16 so this was a potential source of training people to come 17 back in more highly trained than I was at the time I started. 18 Q. So you got a scholarship to go to Western Reserve 19 University. 20 A. Yes. 21 Q. And that scholarship was really because of the 22 relationship between Sharp & Dohme and the head of 23 pharmacology at Western Reserve. 24 A. Oh, I don't think I said that. If I did, I erred. 25 Q. All right. Then correct me, maybe I misunderstood 38 1 you. 2 A. No. I just think that they had a person whom they 3 knew to whom they could refer someone who they thought had a 4 potential, and I think that's the extent of it. 5 My scholarship and fellowship I don't think was 6 given by him other than he had funds that he would be looking 7 for students. I guess it's very much like at most graduate 8 schools. 9 Q. Well, did Sharp & Dohme fund that particular fund? 10 A. No; no; nope. I don't actually know the source of 11 that fund. I think one has to speculate as to the whole 12 spectrum of potential sources of funding. 13 Q. Well, was -- did you sign some type of agreement, 14 or was there an intent -- 15 A. No. 16 Q. -- that you would obtain your M.D. and Ph.D. and 17 return to Sharp & Dohme? 18 A. No. They very specifically just tell you. 19 Q. Beg your pardon? 20 A. They very specifically tell you that when the time 21 comes, well'll see what our wants and needs are. 22 Q. No guarantees? 23 A. That's correct. 24 Q. So you spent two years there in that program. 25 A. Yep. 39 1 Q. Was that a program where you would, after eight 2 years, receive both an M.D. and Ph.D. degree? 3 A. No. In actuality you would first receive your 4 Ph.D., and then you would roll over and complete your M.D. 5 Q. So what courses of study did you take in the two 6 years? 7 A. I took most of all the first two years of medical 8 school courses. 9 Q. So these would be medical school courses as 10 opposed to pharmacology courses or pharm D. courses -- 11 A. Yes. 12 Q. -- or Ph.D. pharmacology courses? 13 A. Yes. 14 Q. You took anatomy? 15 A. Yes. 16 Q. Physiology? 17 A. Yes -- no, I didn't take physiology; I'm sorry. 18 Q. Did you take pharmacology? 19 A. Yes. 20 Q. What other courses did you take during that 21 two-year period? 22 A. Anatomy, neuroanatomy, biochem, histology, 23 microbiology, physical diagnosis; I can't recall beyond that. 24 These are just things that popped up. I can't tell you all I 25 took or what all I didn't take. 40 1 Q. Why did you leave that program? 2 A. Well, I got tired of sleeping on the sofa in the 3 library at night and bleeding rats all night long for various 4 pharmacology studies. I really didn't think I was going to 5 live. 6 Q. Did you not have a place to stay? 7 A. Oh, yeah, I did, but I had work that was assigned 8 to me. I think it's part of the expression, "It was no free 9 lunch." 10 Q. So were they requiring that you work for the 11 university? 12 A. Conduct the studies that were being run within the 13 department, and if they had experiments that conducted -- 14 were conducted throughout the night, such as drawing blood 15 samples and so on, I was elected. 16 Q. Well, is this something you volunteered for that 17 you were doing for money, or were they -- 18 A. No. 19 Q. -- requiring that you do this? 20 A. I was required to do it. 21 Q. Were other students required to do this? 22 A. Yeah, used to have one other guy and I. We used 23 the sofa very well in the library. 24 Q. Why were you required -- you and this other fellow 25 required to do it? 41 1 A. We were the only two in pharmacology at that time, 2 graduate students. 3 Q. Well, I thought you were taking medical school 4 courses. 5 A. I was taking courses given to me, but I was in the 6 Department of Pharmacology. 7 Q. Well, were you working on an M.D. medical 8 doctorate degree, or a Ph.D. pharmacology degree? 9 A. It was going to be a Ph.D. first, and then you 10 would complete the M.D. The course work leading to a Ph.D. 11 in pharmacology at better schools usually involves relatively 12 extensive medical school courses; not always, but usually. 13 Q. Did you work at all? 14 A. Uh-huh. 15 Q. Off of the campus? 16 A. Yes. 17 Q. During this period of time? 18 A. Yes. 19 Q. Tell me about what you did then. 20 A. In the summertime I worked as a carpenter building 21 garages, and I was a spiker on the Nickel Plate Railroad. 22 Q. Were these either summer jobs or part-time jobs? 23 A. Yep. 24 Q. No full-time employment? 25 A. No. 42 1 Q. How many hours of course work did you get at 2 Western Reserve University? 3 A. Blank. 4 Q. Was it called Western Reserve University at that 5 time? 6 A. Yes, yeah. 7 Q. Isn't there a Case Western University? 8 A. Yeah, yeah. Case used to be a separate school, as 9 I recall. I think it was an engineering type of thing, and 10 they merged. I don't know when, but not at that time. 11 Q. Any other jobs that you had while you were at 12 Western Reserve University? 13 A. Nope. 14 Q. Okay. So when you left that program, what did you 15 do? 16 A. Went to -- I was married, got married. 17 Q. When? 18 A. In that period between the two years I was there. 19 Q. Specifically when? 20 A. Well, it had to be in '52. That's a while back. 21 Q. I'm going to let that slide, Dr. Stark, and I'm 22 not going to press you on that question. When I start 23 pressing you later on -- 24 A. You may. 25 Q. -- you remember the one I let slide on the date of 43 1 your marriage. 2 A. Well, then I'll refresh myself so you're not 3 aware. That's okay. 4 Q. What --? 5 A. My wife was from Rochester, New York, and so once 6 we decided that this really was not a way of living, we went 7 to Rochester, New York, and I started working over there. 8 Q. Doing what? 9 A. Well, I worked at Gerber Baby Food. 10 Q. Was that your first job after you left school? 11 A. I knew you were going to ask me that, and I tried 12 thinking. I believe so. I have to put -- I can't put things 13 into perfect chronological order for you. 14 Q. I understand that, and seriously, Dr. Stark, I'm 15 not going to -- it's not my intent to hold you to those. 16 A. I worked for three companies, which I'll tell you 17 that. I worked for Allerton Chemical Company, I worked for 18 Gerber Baby Food, and -- what's the name of the electronics 19 outfit that used to be there that used to make telephones as 20 well and they sold out to General Dynamics? 21 Well, I worked there as a chemist, anyway. I 22 can't even recall their name right now. Those were my 23 activities in there. 24 Q. What years, approximately, did you work for Gerber 25 Baby Food? 44 1 A. Well, let me put it together, if I can, in a 2 rough, chronological set of events. Let me refresh my memory 3 for a moment. 4 If you'll accept an arbitrary division, it would 5 be '54 to '56, '56 to '58, the next one, and then '58 to '60, 6 down the pike. The reason I'm giving you those numbers is 7 because in 1960 I started back to graduate school at the 8 University of Rochester. 9 Q. All right. So approximately '54 to '56 with 10 Gerber Baby Food. 11 A. Yeah; a couple of years at each of them, give or 12 take a little, if you will. I can't give you the exact. I 13 can't recall them. 14 Q. Let's go back to Gerber Baby Foods. 15 What did you do at Gerber Baby Foods? 16 A. I was a supervisor in quality control. 17 Q. Anything else? 18 A. No. 19 Q. Did that have anything to do with research, 20 development or testing of pharmaceutical products? 21 A. No; no. It was strictly the food. 22 Q. You were acting as a chemist or a biochemist in 23 maybe testing. 24 A. Actually I didn't do the testing, I was more 25 involved in the actual quality control, blending of the foods 45 1 to make appropriate combinations of apple sauce so it was the 2 best tasting in the world, making sure there was no excessive 3 amounts of salt for taste. 4 It was a separate biochemical group actually of -- 5 biochemists who actually did analyses. I was not involved in 6 that. 7 Q. Why did you leave Gerber? 8 A. Each job that I took I got a significant raise in 9 pay. 10 Q. And what was it at Allerton Chemical that you did? 11 A. I was -- they called me a coatings chemist. 12 Q. Tell me what that is. 13 A. I used to play with various combinations of resins 14 and solvents and so on to come up with different, unusual 15 finishes that were needed for particular industries. 16 Q. What was Allerton Chemical? 17 A. They were a coatings company. 18 Q. Coating, you're saying; not coding, coating? 19 A. Coating. 20 Q. Like wood coating or --? 21 A. Yes. 22 Q. And these were liquid coatings that would be 23 applied onto products? 24 A. Yes. 25 Q. Were you a coatings chemist your entire period of 46 1 time? 2 A. Yes. 3 Q. Now, did that work at Allerton Chemical in any way 4 involve products that would be consumed by humans? 5 A. No. 6 Can we move on to the third company? I remember 7 their name. 8 Q. Good. Let's write it down before you forget. 9 A. Stromberg-Carlson. 10 Q. Spell that for me. 11 A. S-T-R-O-M-B-E-R-G hyphen C-A-R-L-S-O-N. 12 This is so embarrassing to find these memory 13 lapses, I'll tell you. 14 Q. What did you do at Stromberg-Carlson? 15 A. I had the title of a chemist. 16 Q. What was Stromberg-Carlson? 17 A. They were -- they manufactured telephones, 18 televisions, communications type of things. 19 My involvement was -- at that time it was the very 20 beginning of printed circuitry, and they had just gotten a 21 contract from Ford to make the printed circuits for the Ford 22 radios, and we had to figure out a means to etch and make it 23 work properly and have a printed circuit. They got together 24 bodies. Anybody who had a degree in chemistry of any sort 25 was a candidate. That represented a very significant 47 1 activity for me for the time I was there. 2 Q. It was probably a major contract for this company. 3 A. Oh, yeah, I think so. It was -- I think to them 4 it represented a new era because, you know, well, this 5 contract, they were very involved in government work, and so 6 I assumed that they foresaw all kinds of possibilities. 7 Printed circuitry was just starting, really, and 8 people didn't know it. Today we take it for granted, of 9 course. 10 Q. And what was your job there at Stromberg-Carlson? 11 A. I was involved in trying to figure out protective 12 coatings to put on the part that was not supposed to be 13 etched, recovery of the copper that came off from the copper 14 clad, working on adhesives to hold the copper strongly to the 15 melamine board so it would stand up to humidity and 16 temperature, both; everything to do with a potential 17 developing of new product. 18 Q. And did any of that work have to do with products 19 that would be consumed internally by humans? 20 A. No; no. 21 Q. Did it have -- was it -- it was research and 22 development, I guess. 23 A. Yes. 24 Q. It was experimentation. 25 A. More development -- 48 1 Q. Development? 2 A. -- if you were to ask me. You didn't, but I 3 answered. 4 Q. And all these foods (sic), Gerber Baby Food, 5 Allerton Chemical and Stromberg-Carlson, were all located 6 in -- 7 A. Rochester, yes. 8 Q. Rochester, New York? 9 In the work you were doing for this six-year 10 period, would that be characterized basically as chemical -- 11 working as a chemist? 12 A. Probably, other than Gerber Baby Food, yes. 13 Q. Well, at Gerber Baby Food you were a supervisor in 14 quality control. 15 A. Yeah. That wasn't really a chemist. 16 Q. So you weren't doing pharmacology work or 17 chemistry at that time. 18 A. That's correct. 19 Q. That was sort of a two-year hiatus from your 20 scientific endeavors. 21 A. I had my first exposure to management. 22 Q. All right. And it didn't take long before you got 23 back into becoming a chemist. 24 A. That's correct. 25 Q. But the work at Allerton Chemical and 49 1 Stromberg-Carlson had to do with working as a chemist as 2 opposed to a pharmacologist. 3 A. Yes. 4 Q. But that period of time from 1949 to '51 -- 1951, 5 where you were a pharmacologist at Sharp & Dohme, that was 6 working as a pharmacologist. 7 A. That's correct. 8 Q. What was your next job after leaving 9 Stromberg-Carlson? 10 A. I became a graduate student at the University of 11 Rochester School of Medicine. 12 Q. That began in 1960 -- 13 A. Yes. 14 Q. -- and ended in 1963? 15 A. Correct. 16 Q. And you were -- that's where you were awarded your 17 Ph.D. in pharmacology. 18 A. That's correct. 19 Q. Did you work from 1960 to 1963 while you were at 20 the University of Rochester School of Medicine? 21 A. A little. I didn't have much time, but I worked a 22 little. 23 Q. Anything involving research and development, 24 pharmacology, analyzing drugs or chemicals in that part-time 25 employment that you had? 50 1 A. Yeah. One of the jobs was on Saturday mornings I 2 used to work at the hospital doing analysis for uric acid. 3 Q. You were working in the lab in the hospital? 4 A. Yeah. They used to save all the samples for the 5 last three days, and I would do them on Saturday mornings. 6 Q. Anything else? 7 A. Yeah. I used to pump gas and wash cars at the gas 8 station down the street. 9 Q. Was your wife working at the time? 10 A. Yes, yeah. 11 I had a scholarship at Rochester, too, though. 12 Q. From the University of Rochester? 13 A. Actually I think it was a United States Public 14 Health Service grant. 15 Q. How did you come to get a grant from the U.S. 16 Public Health Service? 17 A. I knew you were going to ask that. Actually, it's 18 a very pleasant story. 19 Q. Good. 20 A. I'll share it with you. 21 Q. Please. 22 A. My next-door neighbor was a professor at the 23 school of medicine in the Department of Pharmacology, and 24 after we both finished mowing our lawns one Saturday, we 25 talked, and he was asking me, "What did you used to do, 51 1 Paul?" and I told him. 2 I said, "The part I think that I've enjoyed the 3 most in all my life was when I did pharmacology at Sharp & 4 Dohme." Then we spoke more and more and more. 5 And then the following Saturday when we finished 6 mowing the lawn, he had me come over and we had some lemonade 7 together and we talked some more. 8 And I was away on a holiday with my wife, and I 9 got a phone call from the head of the Department of 10 Pharmacology asking me if I could stop by the day I got back. 11 And he met with me all morning, then came to my 12 house, and he said, "If you'd like to go back to graduate 13 school to get your Ph.D., I have funds available for a 14 graduate student, and I can give you free tuition, and I know 15 you're married and you have children. I have to know what 16 you need to live on, not what you want to live on, but what 17 you need to live on," and he came up with some funds that 18 were close to what I needed to live on, and I went back to 19 graduate school; and that's probably one of the most exciting 20 things that ever happened to me, outside of my family. 21 Q. Well, had you submitted to them a transcript -- 22 A. No, no. 23 Q. -- or --? 24 A. Oh, that came afterwards. 25 Q. But they gave you the commitment based on that 52 1 discussion that they would give you the tuition -- 2 A. Yeah. 3 Q. -- give you the scholarship -- 4 A. The tuition, yeah. 5 Q. -- assuming that you could -- 6 A. Furnish some records, yes. 7 Q. -- send documents? 8 A. Yes, yes. I just wanted to share it with you. 9 It's one of the more pleasant things -- one of the most 10 pleasant things that happened to me. 11 Q. I agree, I agree. That's not the way I got into 12 law school; I can't tell any kind of story like that. 13 All right. After you got your Ph.D., did you go 14 into employment? 15 A. Yes, I did. 16 Q. All right. Tell me about your first employment 17 after you got your Ph.D. in pharmacology. 18 A. Eli Lilly & Company. I got hired about one year 19 before I graduated. 20 MR. PAUL SMITH: I think this would be a good 21 point to take a quick break. 22 THE VIDEOGRAPHER: Off camera. 23 (Deposition recessed.) 24 (Deposition resumed.) 25 THE VIDEOGRAPHER: On camera. 53 1 BY MR. PAUL SMITH: 2 Q. You said you were hired by Lilly a year before you 3 actually got your Ph.D.; is that right? 4 A. Yes. 5 Q. So that would have been sometime in 1962. 6 A. Yeah. 7 Q. All right. You were doing your Ph.D. at Rochester 8 School of Medicine. I assume that's in Rochester, New York. 9 A. Yes. 10 Q. And what were you doing for Lilly, beginning in 11 1962? 12 A. Nothing. I just had a job waiting for me when I 13 graduated. 14 Q. Oh, they offered you the job, but you were not 15 being paid -- 16 A. No. 17 Q. -- until you graduated. 18 A. No. 19 Q. So you actually started work for them in 1963. 20 A. Yes. 21 Q. Who did you interview with there at Lilly? 22 A. Irwin Slater. 23 Q. S-L-A-T-E-R? 24 A. Yes. 25 Q. What was his position at that time? 54 1 A. He was -- I don't know what the title was. He was 2 in charge of pharmacology. 3 Q. Is he still with Lilly? 4 A. No; he's retired. 5 Q. Is he still alive? 6 A. Yes. 7 Q. Where does he live? 8 A. He lives in Naples, Florida. 9 Q. Oh, really? Do you still see him? 10 A. Yes. 11 Q. How old of a man is he now? 12 A. Oh, I'm guessing; seventy, plus or minus. 13 Q. Do you have his address? 14 A. No, but I can find my way to his house by road. I 15 see him once a year regularly when I come down. 16 Q. Do you have his address written maybe in an 17 address book or something? 18 A. No, I don't. I actually just dig up his phone 19 number every time and call is all I do. He's in the phone 20 book, if that helps you. 21 Q. In Naples, Florida? 22 A. Yeah. 23 Q. But at the time he interviewed with you, he was in 24 charge of pharmacology at Eli Lilly & Company. 25 A. Yes; yes. 55 1 Q. Was he an officer of the company, executive with 2 the company? 3 A. Those are two different terms you just used. 4 Q. I know it. Start with officer. 5 A. I don't believe so. 6 Q. Was he an employee -- I mean an executive? 7 A. If you'll define "executive," or I'll just do it 8 to save us time. 9 Q. Good. 10 A. At director level, I consider that an executive. 11 Q. Was he the one that actually offered you the job 12 in 1962? 13 A. Yes. 14 Q. Anybody else that you interviewed with at Lilly? 15 A. Jack Mills was in the room. 16 Q. M-I-L-L-S? 17 A. Uh-huh. 18 Q. And what was his job title? 19 A. I don't know. He was a chemist. 20 Q. Do you know if Mr. Mills is still with Eli Lilly & 21 Company? 22 A. I know he's not. 23 Q. What is he doing now? 24 A. He's deceased. 25 Q. When did he die? 56 1 A. Before '84. 2 Q. Anybody else that was involved in your hiring, Dr. 3 Stark? 4 A. Another person who I met in the course of visiting 5 and interviewing was Dr. Ray Fuller. 6 Q. F-U-L-L-E-R? 7 A. Yes. 8 Q. And what was his position at that time? 9 A. I don't know his title. He was in the Department 10 of Pharmacology. He was there when I came down for a visit 11 before I started, I remember. He was not present at the 12 initial interview when I was offered the job. 13 Q. And where is Dr. Fuller now? 14 A. I believe he's still with Lilly. 15 Q. And what's his position? 16 A. He's in the Department of Pharmacology; I don't 17 know what his title is. 18 Q. So did you move to Indianapolis in 1963? 19 A. I did, sir. 20 Q. And what was your first job with Eli Lilly? 21 A. I was a pharmacologist; I was a bona fide one now. 22 Q. You were "Dr. Stark" by then. 23 A. Yes, sir. 24 Q. What department were you hired to work in? 25 A. Department of Pharmacology. 57 1 Q. Is the Department of Pharmacology, or was it at 2 that time, broken down into several sub-departments? 3 A. I don't think there were any. I don't recall any 4 official separations. 5 Q. What were you doing at first? 6 A. Pretty much what I was doing at Rochester. I was 7 still working on transmitters and mechanisms of action and so 8 on. 9 Q. Were you a neuropharmacologist at that time? 10 A. Yes, sir. 11 Q. Were you a neuropsychopharmacologist? 12 A. Yes, sir. 13 Q. So the transmitters and mechanisms of action that 14 you were working on would have been neurotransmitters; is 15 that right? 16 A. I was -- I have spent the rest of my career 17 working in the central nervous system area. 18 Q. Who was your supervisor, immediate supervisor, 19 when you first started? 20 A. Irwin Slater, Dr. Slater. 21 Q. And were you working on neurotransmitters or 22 mechanisms of action in connection with any particular drug? 23 A. Not initially, no. I just was pursuing behavioral 24 changes that took place, and as time evolved I started 25 working with the various chemists, once again, just as we 58 1 discussed previously, with various chemical entities and 2 trying to develop tests for them. 3 Q. Well, how long did you work just where you were 4 doing sort of academic work on neurotransmitters at Lilly 5 where you weren't working on any particular compound? 6 A. I can't answer that for you on a time basis. I 7 don't recall. 8 As you can imagine, research is an evolving type 9 of thing, and I couldn't -- I really could not put my finger 10 on even an approximate date for you, or else it would be 11 extraordinarily approximate. 12 Q. Would you remember that for a period of time your 13 work was work in the general field of neurotransmitters and 14 you weren't working on any particular compound? 15 A. Yes, there was a period of time, but I can't 16 recall how long. 17 Q. Would that have been a period of months or of 18 years? 19 A. I'd be guessing. 20 Q. Were you working toward completing some particular 21 project or goal initially while you were at Lilly? 22 A. I think when you do research, there's always a 23 goal. I have to answer your question, so the answer has to 24 be yes to the way you phrased the question, yes. 25 Q. And I guess maybe the reason I phrased the 59 1 question the way I did is, you know, certainly I know that 2 most companies would be interesting -- interested in their 3 scientists doing research in working on theoretical concepts, 4 but I would assume that they would want that work to be 5 directed at least eventually toward something that they could 6 use in some manner. 7 A. I think that's a very accurate statement, what you 8 just made. 9 Q. They were paying you, and I assume they wanted to 10 benefit Lilly by virtue of their paying you. 11 A. I think that's accurate, too. 12 Q. And expected you to, in this theoretical research 13 before you began working on any particular compound, to come 14 up potentially with something that would be of benefit to Eli 15 Lilly & Company. 16 A. Rephrase that for me, if you would. 17 Q. They were paying you --. 18 A. You lost me. I'm not --. 19 Q. Okay. All right. They were paying you to come up 20 with something that would be of benefit to Lilly while you 21 were doing this relatively academic research. 22 A. I think more accurately, they would hope that it 23 would lead to something constructive. I think that's the 24 basis of research, so we should put it in that context, if 25 it's okay with you. 60 1 Q. I would assume that would be a reasonable hope and 2 belief by Lilly -- 3 A. Absolutely. 4 Q. -- that it would lead to something constructive. 5 A. Absolutely. 6 Q. Obviously for you to be doing research while at 7 Lilly on a bar of soap wouldn't necessarily be something that 8 Lilly would be interested in. 9 A. That is very reasonable and probably very accurate 10 to boot. 11 Q. In other words, they had you directed into some 12 particular area or field. 13 A. No. 14 Q. Okay. 15 A. My work was in the central nervous system, and 16 they had an interest in the central nervous system, and 17 therefore I did work and they supported my endeavors. 18 Q. What was your -- what was their interest, as far 19 as you knew, in your work in the central nervous system on 20 the theoretical basis? 21 A. I think as stated at all times, probably by my 22 supervision of the company, is we would like to understand 23 how various punitive transmitters work so that indeed we can 24 alleviate various disease entities. 25 Q. At the time you came on with Lilly in 1963, did 61 1 they have some compounds that they were researching having to 2 do with neurotransmitters in alleviating particular problems 3 that might be encountered? 4 A. Literally thousands. This is a large research 5 organization, I guess, you know, a lot of people, a lot of 6 chemists. 7 Q. I'm talking about the neurological -- 8 neurotransmitters. 9 A. And I answered you, literally thousands. 10 Q. Thousands of people? 11 A. No, compounds you asked about, I believe; yes. 12 Q. Okay. You did your theoretical work for a period 13 of time. 14 A. Yes. 15 Q. You don't know whether it was months or years; is 16 that right? 17 A. Not really. If you'll accept the premise that 18 there was an evolution moving from straight theoretical on, 19 then if you'll do without the time frame, I will have 20 communicated to you what your question was. 21 Q. Do you remember what your first compound was? 22 A. No. I did not work on any specific compound, so I 23 think we should probably go from that point. 24 Q. Then you're going to have to explain to me, then, 25 what work you were doing. 62 1 A. Probably identical to what I described to you at 2 Merck -- at Sharp & Dohme before it was Merck, Sharp & Dohme. 3 Chemists start with various basic structures, and 4 my job was to eventually help evaluate them, those compounds. 5 Those are not any chemical compound that's already been 6 picked and dried. 7 So when you asked me what the compounds were, and 8 I said literally thousands, I think a good medicinal chemist 9 is only limited by his imagination, but that's my opinion. 10 I'm not being facetious with you, because I don't 11 know your knowledge of the pharmaceutical industry, so I 12 didn't want to be facetious or a wise guy about it to you. 13 Q. No, you can make the assumption that I have no 14 knowledge of the pharmaceutical industry other than a 15 basement there at Lilly that has some documents. 16 A. I don't believe that, sir. I think you're a very 17 knowledgeable man. 18 Q. The work there within was pure research and 19 development. 20 A. Yes; yes. 21 Q. It didn't have to do with clinical trials. 22 A. No, not at that point in my career at all. 23 Q. It didn't have to do with protocols. 24 A. Not at that point in my career at all. 25 Q. Didn't have to do with outside investigators? 63 1 A. Not at that point in my career at all. 2 Q. How long did you do this research and development 3 work for Lilly? 4 A. Well, I have to say that clinical trials is part 5 of research and development in my mind, but if you want to do 6 basic bench work as opposed to clinical -- 7 Q. Okay. 8 A. -- somewhere in the order of fifteen years; 9 fourteen, fifteen years. 10 Q. Say maybe '77 or 1978. 11 A. If that's what it adds up to, yes. I'm basing all 12 this on the fact that I was employed at Eli Lilly for 13 twenty-one years, and I broke out in round numbers six years 14 in clinical and fifteen years in basic, plus or minus. 15 Q. Did you say six years in clinical? 16 A. Round numbers. 17 Q. So you were with Lilly from 1963 until 1984? 18 A. That's correct. 19 Q. Did Dr. Slater continue to be your supervisor 20 throughout that period of time that you were doing what you 21 described as basic bench work? 22 A. Yes. 23 Q. And after a period of time while you were doing 24 that basic bench work, you began working on compounds -- 25 A. Yes. 64 1 Q. -- and analyzing different aspects of the 2 compounds and different actions of the compounds in a 3 laboratory setting. 4 A. That's correct. 5 Q. Did you at any time do any work on fluoxetine up 6 from 1963 until 1978 when you completed that time that you 7 were doing basic bench work? 8 A. Yes. 9 Q. When did you first work on fluoxetine? 10 A. I don't know when. 11 Q. Can you give me an approximation? 12 A. After 1970. I'm sorry, because I have to allow 13 myself that much latitude because I don't have any idea when 14 it was. 15 Q. That's fine. 16 What was your first work with fluoxetine? 17 A. I can't tell you, sir. 18 Q. Before 1970? 19 MS. FRIEND: Excuse me, Mr. Smith. May I just 20 interrupt a minute. 21 I took a look at the monitor, and I'm going to 22 ask, this lighting is so bad, it's hard to even see his 23 face when he's sitting there. If you could --. 24 MR. PAUL SMITH: Well, let's turn the light back 25 on a minute. 65 1 THE VIDEOGRAPHER: The picture is going to be 2 fine. 3 MR. PAUL SMITH: I beg your pardon? 4 THE VIDEOGRAPHER: The picture will be fine. 5 You want to go off the record? 6 MR. PAUL SMITH: Yeah. 7 (Deposition recessed.) 8 (Deposition resumed.) 9 THE VIDEOGRAPHER: On camera. 10 MR. PAUL SMITH: Will you read the last question, 11 please. 12 (Last question and answer read back by the 13 reporter.) 14 BY MR. PAUL SMITH: 15 Q. Before 1970 were you aware that Eli Lilly & 16 Company had either under patent or under investigation a 17 compound that later became known or was known as fluoxetine? 18 A. I can't relate to the dates. 19 Q. What's your understanding of what the history of 20 fluoxetine as a compound with Lilly was? I understand you 21 first worked with it in approximately 1970, but what is your 22 understanding concerning the history of fluoxetine at Eli 23 Lilly & Company? 24 MR. FREEMAN: I think he answered the question, 25 that it was 1970 or after, something of that. 66 1 A. Yeah, because I don't know when it was, and that's 2 a very arbitrary number. In fairness, I have to qualify that 3 for you. 4 Q. In fairness, I won't hold you to it, then. 5 A. Thank you. 6 I'm sorry, you must pick up with me again. 7 Q. What's your understanding of the history of 8 fluoxetine with Eli Lilly & Company? 9 A. Can you be more specific so I know how to answer 10 you? 11 Q. Well, did you know that fluoxetine was a compound 12 that Lilly had some right to investigate? 13 A. Yes. I don't know when I knew this. 14 Q. What's your understanding of the background of how 15 Lilly got fluoxetine or how Lilly became interested in 16 fluoxetine as a product or as a compound either to 17 investigate, produce or in any way be examined as a potential 18 compound for any purpose? 19 A. You've covered history, sir. 20 Q. What I want you to do is tell me what you know 21 about the history of fluoxetine; who invented it, when was it 22 invented, how did it --? 23 A. One question at a time and I'll answer them, okay, 24 because if we're going to work together, we have to go 25 together. 67 1 Q. Yeah, I'm just trying to -- I know I asked you 2 five questions, but I'm just trying to give you an idea of 3 where I'm going. 4 A. I don't recall the origin of fluoxetine, and keep 5 walking me. I'll answer you, I really will. 6 Q. Okay. 7 A. Okay. 8 Q. So do you recall who developed fluoxetine as a 9 compound? 10 A. No. 11 Q. Do you recall whether or not there was a 12 particular group of individuals that had been working on 13 fluoxetine as a compound before you began working on 14 fluoxetine? 15 A. Yes. The first name that I know of was Ray 16 Fuller. 17 Q. And Ray Fuller was at that time -- what was his 18 position? 19 A. I don't know. He was in the Department of 20 Pharmacology is the best I can -- I don't really -- we 21 have -- you know, all corporations have all series of names, 22 and I really don't know all of the various titles there were. 23 Q. Do you know what fluoxetine was being investigated 24 for originally? 25 A. It was a chemical class that was being evaluated. 68 1 Q. What chemical class? 2 A. It was called serotonin reuptake inhibitors. 3 Q. And what was it being evaluated for? 4 A. I don't know precisely what Ray was doing, except 5 he does very extensive biochemical work and this was his area 6 of expertise. 7 So you asked me my best recollection; that's my 8 first recollection. 9 Q. Had you heard of serotonin uptake inhibitors 10 before you began work at Eli Lilly & Company? 11 A. No. 12 Q. Had you heard of serotonin -- 13 A. Yes, sir. 14 Q. -- before you began working -- 15 A. Yes, sir. 16 Q. -- at Lilly? 17 A. Yes, sir. 18 Q. Explain to us what your impression is or what your 19 understanding was of serotonin. 20 A. That it was a punitive central nervous system 21 transmitter. 22 Q. When you say "punitive," it was questionable or 23 understood to be a --? 24 A. I think the term "punitive" means that it could 25 be, but it's not proven. 69 1 Q. Has that been proven? 2 A. In some people's minds. 3 Q. In yours? 4 A. I have yeas and nays. 5 I don't know how to spell that. 6 Q. Do you -- did you have an understanding with any 7 more specifics of what Dr. Fuller was investigating 8 fluoxetine for or the potential uses he felt like it might be 9 of benefit for? 10 A. I only know of his interest in the central nervous 11 system, and I sus -- and I would have every reason to think 12 that he, like I, would look at any punitive transmitter and 13 say, "Is this a potential chemical entity that can be altered 14 to be beneficial in some way?" 15 Q. To become a mood-altering drug? 16 A. I don't know if it's mood-altering. I don't like 17 that expression, because it has all kinds of connotations. 18 Q. I didn't -- I'm sorry, my connotation did not mean 19 like LSD or something like that. 20 A. Well, I look for any punitive transmitter to be 21 able to affect behavior, and therefore if you have behavior 22 that is abnormal or undesirable, if one can reverse that 23 process to make it desirable or pleasant, depending on what 24 type of terminology, then that to me is a goal. 25 I never sat down with Ray, you see, and say, "Tell 70 1 me why you're working on this." 2 So I'm not sidestepping you, because you asked me 3 a very definitive question that I couldn't really answer 4 except as I did just now. 5 Q. Do you remember what your first work was with 6 fluoxetine? 7 A. No, I don't. 8 Q. Do you -- what is your recollection of the first 9 work that you did, that you can recall? 10 A. I can't, except that it was in some animal models 11 that I had. I couldn't even tell you specifically which one 12 of the several that I had helped develop there. 13 Q. Can you give me an idea of when this would have 14 been? 15 A. After '70, and I am not being difficult for you at 16 all. I hope we go on that understanding. 17 Q. Did you have an understanding concerning whether 18 or not at the time you first began your work in animal models 19 with respect to fluoxetine, that you felt like it was being 20 investigated to affect individuals who were depressed? 21 A. No, I don't think I had that originally. It was 22 just a matter of evaluating what it did do, the various 23 changes that would take place. I think everyone was very 24 open-minded, actually. 25 Q. Do you remember what it was -- what you were 71 1 doing? You say you were doing animal models. 2 A. Yes. 3 Q. Do you remember what, with respect to the animal 4 models, you were doing? 5 A. I can tell you the animal models that I had; I 6 couldn't tell you which one I went into. 7 I had muricidal rats, I had septal-lesioned rats 8 and I had self-stimulating animals, I had dog observation, 9 mouse activity; I had a typical behavioral-type pharmacology 10 lab, some unique tests, but that's about all. 11 Q. And you were administering fluoxetine to various 12 animals over a period of time to measure certain responses of 13 those animals to the dosages of fluoxetine? 14 A. At such times that I worked with fluoxetine, that 15 would have been the goal, yes. 16 You know, you're making -- I don't want you to say 17 that this was a fluoxetine program. I did research with 18 various and sundry chemical entities, and they were all 19 evaluated. 20 Q. Were they being evaluated together, or were 21 they --? 22 A. Yes. In any given time there would be a multiple 23 battery of chemical entities being evaluated. 24 Q. All right. So for seven or eight years, would it 25 be accurate to state that you did basic bench work in 72 1 evaluation of fluoxetine? 2 A. I don't think so. 3 Q. All right. 4 A. I think -- we have to go back here. I think 5 there's a misunderstanding. 6 Q. Okay. 7 A. At sometime after 1970 - and I don't know when it 8 was, it could have been 1977, couldn't it - I did work with 9 fluoxetine. I do not recall when I did work with it, when I 10 started to, no. 11 Q. Do you remember whether an application had been 12 made with the Food and Drug Administration to investigate 13 fluoxetine? 14 A. Do I recall? Oh, yes, I do, yes. 15 Q. All right. When is -- what is your recollection 16 of when that application was made? 17 A. Sometime after I was doing clinical research; the 18 exact date, I don't recall. So it would be probably sometime 19 after '77, '78, in that range; I don't know when, though. 20 Q. Well, by that can we say that you would have been 21 involved or that work that you had initially started would 22 have been done in the preclinical investigation of 23 fluoxetine? 24 A. I can't tell you whether the application went in 25 before I came out and I was still doing some evaluations, or 73 1 if it was after I was out and doing clinical evaluations, 2 because I was doing clinical evaluations with others 3 compounds while I was still in the lab before I moved over 4 full time to the clinical group. 5 Q. You're not implying, though, that you were working 6 exclusively on fluoxetine. 7 A. When? 8 Q. When you first started your -- these animal models 9 where you were administering fluoxetine and other compounds 10 on rats, dogs and mice to measure their response. 11 A. In preclinical I never worked exclusively on 12 fluoxetine. 13 Q. I take it that in '77 or '78 your work with Lilly 14 changed from basic bench work, and you went into the clinical 15 investigation of drugs. 16 A. That is correct. 17 Q. And you did that for six years, until 18 approximately 1984. 19 A. Yeah, six or seven years. I can't recall if it 20 was '77, '78, necessarily. 21 Q. And what drugs were you working on during that 22 six-year period? 23 A. I did work on nabilone -- 24 Q. Spell that for us. 25 A. N-A-B-I-L-O-N-E. 74 1 -- tomoxetine, an antipsychotic whose name I can't 2 recall, and fluoxetine. To the best of my knowledge and 3 recollection, those were the four compounds I worked on in 4 the clinical area. 5 Q. And none others? 6 A. To the best of my recollection. 7 Q. When you were in the preclinical phase, what other 8 drugs did you work on other than fluoxetine, or compounds may 9 be the accurate term? 10 A. Well, the compounds would all have numbers, and I 11 probably would say that there's somewhere in excess of a 12 thousand. 13 Q. All right. Can you tell me whether any of those 14 compounds that's in excess of a thousand became drugs that 15 Lilly produced? 16 A. Nabilone. 17 Q. Any others? 18 A. "Became a drug," define that for me. 19 Do you mean that went to market? 20 MR. FREEMAN: You mean became approved for use? 21 MR. PAUL SMITH: Right, right. 22 A. (Cont'g) Nabilone. 23 Q. N-A-B-A-L-O-N-E-? 24 A. N-A-B-I-L-O-N-E. Cesamet was the trade name, 25 C-E-S-A-M-E-T. 75 1 Q. What is it? 2 A. I'm sorry? 3 Q. What is Cesamet? 4 A. It's a cannabinoid. 5 Q. Translate. 6 A. It's a chemical cause of compounds called 7 cannabinoids. 8 Q. Is it a neurotransmitter? 9 A. Is it a neuro -- no. 10 Q. Does it affect neurotransmission? 11 A. If behavior is controlled exclusively by 12 neurotransmission, then the answer is yes, because this will 13 affect behavior. 14 It was approved for use primarily, however, as an 15 antiemetic in cancer chemotherapy, which is a central nervous 16 system phenomenon. 17 Q. So it's not used as a drug to affect behavior or 18 mood. 19 A. That is correct. 20 I don't know if it is still marketed or not. It 21 has never, to the best of my knowledge, been marketed in the 22 United States, but I'm only an ex-Lilly employee, so you'll 23 have to know I left in '84. 24 Q. But nabilone or Cesamet was originally 25 investigated as a neuropsychotropic drug. 76 1 A. I'm thinking, because I want to answer you 2 accurately. I'm not sure, but I believe so. 3 Q. But it was never marketed by Lilly as a 4 neuropsychotropic drug. 5 A. Correct. 6 Q. It was marketed as a drug to assist patients or as 7 a treatment for nausea in patients who were undergoing cancer 8 therapy. 9 A. That is correct. 10 Q. What type of neurological effects was it having on 11 patients or behavioral effect was it having? 12 A. I can only tell you the results of studies that 13 were conducted. 14 Q. All right. 15 A. And it appeared to be effective as an antianxiety 16 compound in the behavioral area. 17 Q. Who was your supervisor during your six years as 18 an employee doing clinical trials for Eli Lilly & Company? 19 A. They varied, and I can't remember all the people 20 who were involved. One name was Ian Shedden. 21 Q. I-A-N? 22 A. I-A-N, S-H-E-D-D-E-N, I think. 23 Q. Who's he? 24 A. I'm sorry? 25 Q. What was his position at the time? 77 1 A. I don't remember if he was a director or 2 vice-president or what. He was in the medical research area. 3 Q. Is he still alive? 4 A. I don't know. 5 Q. Do you know whether he's still with Lilly? 6 A. Oh, I know he's not. I know he's somewhere in 7 England; he was somewhere in England. 8 I don't know whether he's still alive or not, 9 though. That was your question. 10 Q. Who else supervised your work during this six-year 11 period that you were involved in the clinical trials? 12 A. Cecil Bendush. 13 Q. B-E-N -- 14 A. -- D-U-S-H. 15 Q. What was his position at the time? 16 A. He was probably a director. I don't know the 17 title. We had too many titles. I can't tell you. 18 Q. Is he still with Lilly? 19 A. No. 20 Q. Do you know where he is? 21 A. No. Somewhere in Jersey. 22 Q. You think he's still alive? 23 A. Yeah. 24 Q. Any other supervisors that you had during this 25 six-year period of time that you were doing clinical --? 78 1 A. Bob Zerbe. 2 Q. Z-E-R-B-E? 3 A. Yes. 4 Q. What was his position at the time? 5 A. You must not ask me those titles. 6 Q. Is he still with Lilly? 7 A. Yes, I believe so. 8 I looked at you to see if you were going to nod 9 yes or no, because I haven't seen him in some time. 10 Q. When's the last time you saw Dr. Zerbe? 11 A. Four years. 12 Q. What were the circumstances of you seeing Dr. 13 Zerbe four years ago? 14 A. Meeting with him to see about doing potential 15 other studies for Eli Lilly. 16 Q. With respect to Prozac? 17 A. I'm not fussy; any compound, any central nervous 18 system compound. 19 Q. Did you get an assignment? 20 A. Not since that meeting, no. 21 Q. Did you get an assignment at that meeting? 22 A. No. 23 Q. Well, have you or your company not done any work 24 for Lilly in the last four years? 25 A. No. Wait -- no, no; probably finished. 79 1 Q. Beg your pardon? 2 A. I said it was probably -- the stuff that we did 3 was probably finished by that time, I'm guessing. 4 Q. Any other supervisors that you had during that 5 last six years that you were with Lilly as a clinical 6 inves -- would you be called a clinical investigator -- 7 A. No. 8 Q. -- during that period of time? 9 A. No. 10 Q. You would have been called probably a 11 pharmacologist doing work with respect to clinical 12 investigations? 13 MR. FREEMAN: Monitor would be the term. 14 A. I would be a medical monitor is what I was. 15 Q. Thank you. Medical monitor. 16 And you were a medical monitor the last six years? 17 A. Roughly. 18 Q. Monitoring clinical trials? 19 A. That is correct. 20 Q. Monitoring clinical trials having to do with those 21 drugs that you listed earlier, nabilene (sic)? 22 A. Nabilone. 23 Q. Nabilone, hema --homa -- I can't read my writing. 24 You got it? Tomoxetine -- 25 A. Yes, sir. 80 1 Q. -- fluoxetine -- 2 A. Yes. 3 Q. -- and one other antipsychotic -- 4 A. That's correct. 5 Q. -- that you don't recall the name of. 6 A. That's correct. 7 Q. That's exclusively what you were doing those last 8 six years; that's exclusively what you --? 9 A. Doing clinical monitoring? 10 Q. Right. 11 A. Yes. 12 Q. As a medical monitor. 13 A. That's the term that we use, yes, as opposed to 14 animal monitor. 15 Q. I'm not sure I finished up. 16 Any other supervisors? 17 A. I reported into Leigh Thompson. 18 Q. Who? 19 A. Leigh Thompson. 20 Q. L-A-Y? 21 A. I think it's L-E-I-G-H. 22 Q. All right. 23 A. I don't know if there's a P in it or not, 24 Thompson. 25 Q. I'm going to ask you again, what was Thompson's 81 1 title? 2 A. Don't know. 3 Q. But Thompson was overseeing medical monitors at 4 that time, at some time there. 5 A. I think he was overseeing the medical division. 6 Q. Any other supervisors? 7 A. Not that come to mind. 8 Q. Why did you leave Lilly in 1984? 9 A. To start my own company. 10 Q. Well, why did you want to start your own company? 11 A. We're going to be a little while, folks. 12 I think I'm entrepreneurial in nature, enjoy being 13 my own boss, I enjoy the rewards of success and I'm willing 14 to take the heat of failure. 15 Q. Did you ever think about practicing law 16 representing plaintiffs? 17 A. I assume that was rhetorical. 18 Q. It was the heat of failure that --. 19 Well, were you dissatisfied with Lilly? 20 A. Pardon me? 21 Q. Were you dissatisfied working for Lilly? 22 A. No, I don't think so. I'll phrase it to you in a 23 way that I finally had very good insight. 24 Someone said to me, "Don't you wish you had gone 25 into business sooner and started this thing? You're 82 1 obviously so happy and thrilled. Were you unhappy at Lilly?" 2 I said, "No, not really. I just never knew how 3 happy I could be. I didn't know what level I could ever 4 obtain of absolute joy." 5 I'm absolutely thrilled with what I'm doing right 6 now. 7 Q. You just didn't recognize that you would be as 8 happy as you are. 9 A. Id didn't know there was another plateau to be 10 attained. I'm smiling because I really am very happy in 11 general. 12 Q. Well, is it the nature of the work that you like 13 better, or is it the financial reward that you like better? 14 A. Both. 15 Q. Are you spending less time now working than you 16 were when you were with Lilly? 17 A. Unfortunately, not. 18 Q. The hours aren't better. 19 A. No, they aren't, sir. 20 Q. But the pay is. 21 A. On sometimes. 22 Q. Is the job more challenging? 23 A. Broader. 24 Q. Broader in what sense? 25 A. I have a chance to address the questions, the 83 1 problems, the research and development problems of 2 essentially the entire pharmaceutical industry where it 3 pertains to the central nervous system exclusively, and it's 4 a very broad range of questions and problems that are tossed 5 at me, and I find this fulfilling. 6 Q. Well, do you still direct your attention to 7 neuropsychopharmacological problems? 8 A. Yes, I do. 9 Q. But your company and individuals that work for you 10 in your company address broader problems, or is your company 11 exclusively dealing with neuropsychopharmacological products? 12 A. Central nervous system, which would include 13 neuropsychopharmacological. It would include epilepsy, 14 stroke, if you were to -- pain; that's all part of the 15 central nervous system. 16 I don't know if you define that as 17 neuropsychological or not in nature. 18 Q. And you started this company in 1984? 19 A. Yes, sir. 20 Q. It's now 1993, so it's been in existence nine 21 years. 22 A. Yes, sir. 23 Q. But the company's home office is in California? 24 A. Yes, sir. 25 Q. And you're here in Florida? 84 1 A. Yes, sir. 2 Q. How do you run the company a continent away? 3 A. We have -- we organized, we set it up that if 4 necessary I would move to San Diego. I continue living 5 actually in Indianapolis, is my primary base, my home. 6 Q. How come? 7 A. I had family and roots there at that point in 8 time. If needed, my wife and I were going to move to 9 California; if not, we would stay where we were. 10 I would say that probably ninety-five percent of 11 the pharmaceutical industry as we know it, not the Bio-Tech 12 and the biochemical industry that is evolving now, exists 13 from Chicago east. 14 My interaction is primarily with the medical 15 directors and management of the pharmaceutical industry. It 16 actually is extraordinarily far more effective for me to be 17 able to deal with them and their problems and help set up 18 programs where I'm at, and we have very efficient and 19 effective help. My partners are all out in San Diego, and 20 so --. 21 Q. Who are your partners? 22 A. Well, until recently the founders of the company 23 were Robert Budetti and John -- 24 Q. Spell that. 25 A. B-U-D-E-T-T-I. 85 1 Q. B-U-D-E -- 2 A. -- T-T-I. 3 -- John Feighner -- 4 Q. F-E-I-G-H-N-E-R. 5 A. G-H-N-E-R-. 6 -- and myself were the original founders of the 7 company. 8 Q. All right. But you have additional partners now? 9 A. A young man came in and joined us named Kevin 10 Keim, K-E-I-M. 11 Q. All right. And the name of this company is -- 12 give it to me again. 13 A. International Clinical Research Corporation. 14 Q. Why is it based in San Diego? Did Mr. Budetti or 15 Mr. Feighner -- 16 A. -- both live there; and when we first started, we 17 had an offer of some free space and desks, and it was 18 extraordinarily important when we first started business 19 having free office space, and as well the group that I was 20 joined with had no intention of moving east, whereas, I was 21 open to the possibility of moving west, the most logical move 22 if I was willing to go there and they weren't willing to come 23 here, and we were going to join to do it there. 24 Q. I know you've owned a home here in Sanibel for, 25 what did you say, eight years? 86 1 A. Fourteen years. 2 You asked me how long I was here as a part-time 3 resident. Up until then I used to merely vacation here. 4 Q. How long have you been interested? I mean, did 5 you come even when your children were children to Sanibel, 6 Southwest Florida? 7 A. Yeah, we used to come to Southwest Florida. 8 Q. Is this an area that you always wanted to sort of, 9 quote, retire, end quote, to? 10 A. I don't know if I want to retire until my brain 11 turns to mush, but --. 12 Q. That's why I put "retirement" in quotes. 13 A. Thank you. 14 I enjoy spending significant time here and 15 vacationing here. 16 We came -- started coming down to the 17 Venice/Sarasota area, actually, back in '74 when indeed the 18 children were still at home, some of them, and I have become 19 a property owner here since 1979. 20 Q. How many employees are now employed by 21 International Clinical Research Corporation? 22 A. If you'll take a round number, fifty. 23 Q. And what does that company do? 24 A. We conduct clinical trials in the central nervous 25 system area for the pharmaceutical industry. 87 1 Q. And is that what they've been doing since 1984? 2 A. Yes, sir. 3 Q. How did you meet Mr. Budetti? 4 A. Dr. Feighner introduced me to him. 5 Q. Is Budetti a medical doctor, Ph.D.? 6 A. No, no. He's an -- he's a smart business type; 7 he's an M.B.A. from Harvard. He tells me this all the time. 8 Q. Well, does he have any knowledge concerning the 9 central nervous system or investigating drugs used? 10 A. Yes, I think so. 11 Before he had had sev -- many years of experience 12 actually in clinical research and so on. He was the 13 president -- I'm not sure. He was the president, I believe, 14 of Feighner Research Institute is how he first came out to 15 California. He used to be at Yale Medical School before 16 that. 17 Q. Budetti had been at Yale Medical School? 18 A. Yes. He was working there as a controller, I 19 believe, and then he came out to head up the financial 20 aspects of Feighner Research Institute, which has been in 21 existence twenty years, round numbers. I don't know the 22 exact number. 23 Q. So Budetti and Feighner were working together -- 24 A. Yes. 25 Q. -- in an entity called Feighner Research 88 1 Institute -- 2 A. Yes. 3 Q. -- which has been in existence for, you say, 4 twenty years? 5 A. Yeah. He's only been there -- well, he's probably 6 been there twenty years. He's been with us for nine years 7 and he was there for almost ten years before we got married, 8 so --. 9 Q. Budetti? 10 A. Yeah. So he's been out in California for a long 11 time. 12 Q. And Budetti has got a Harvard M.B.A. -- 13 A. Yep. 14 Q. -- and worked at Yale Medical School -- 15 A. Yep. 16 Q. -- as the controller? 17 A. No. He was in the controller -- I think he was an 18 assistant controller, but I'm not positive. 19 Q. Uh-huh. And --. 20 A. Then he came out to California, and he was at 21 Feighner Research Institute working until our company 22 started. 23 Q. Who came up with the company starting, your 24 company, International Clinical Research Corporation, you or 25 Feighner or Budetti? 89 1 A. Try me again. I'm sorry. 2 Q. Whose idea was International Clinical Research 3 Corporation? 4 A. I approached Dr. Feighner after I had known him 5 for many years and asked him if he'd have an interest in 6 helping me form a company; and our conversation progressed, 7 and he introduced me to Bob Budetti since neither one of us 8 really had the appropriate smarts from a business aspect, and 9 the three of us joined forces and formed our company. 10 Q. Well, is there still a Feighner Research Group, or 11 has it been merged into International Clinical Research? 12 A. Oh, no; it's a totally separate entity. 13 Q. In what respect? 14 A. It has nothing to do with International Clinical 15 Research. It's an independent investigator. They do studies 16 for all the pharmaceutical industry, either under contract to 17 us, under contract direct through the pharmaceutical firm, or 18 to other CRO's, even. There are other organizations such as 19 ours. 20 Q. Okay. So Feighner Research Institute might work 21 for International Clinical Research Corporation. 22 A. Yeah. 23 MR. PAUL SMITH: Okay. We need to take a break. 24 You all want to get some lunch? 25 (Deposition recessed.) 90 1 (Videotape One ended at 11:45 a.m.) 2 (Deposition resumed.) 3 (Videotape Two started at 1:06 p.m.) 4 THE VIDEOGRAPHER: On camera. 5 BY MR. PAUL SMITH: 6 Q. Dr. Stark, before we broke for lunch we were 7 talking about International Clinical Research Corporation and 8 your relationship with Dr. -- is it Dr. Feighner? 9 A. Yes. 10 Q. And you first met Dr. Feighner when? 11 A. Probably around 1978, in that area. 12 Q. At that time you were with Lilly. 13 A. Yes. 14 Q. And what was Dr. Feighner's position at that time? 15 A. He was a clinical investigator who did clinical 16 trials for the pharmaceutical industry. 17 Q. Was he an investigator with his company called 18 Feighner Consultants -- Feighner Research? 19 A. He was with Feighner Research Institute. 20 Q. Institute; all right. 21 And that had been -- has been in existence -- 22 Feighner Research Institute has been in existence for 23 approximately twenty years that you know of. 24 A. Yeah, I'd say probably at least that. 25 Q. Was Dr. Feighner doing work for Lilly? 91 1 A. He had not done work for Lilly that I'm aware of; 2 and I qualified my statement because there were a few other 3 psychotropic drugs that Lilly had, as, for example, 4 nortriptyline. 5 I have no knowledge of whether he participated in 6 any studies on that. I knew of him from other sources. 7 Q. Was Feighner interested in neuropsychological 8 research? 9 A. Yeah. 10 THE WITNESS: That's really a pain in the neck. 11 MR. FREEMAN: What is that? 12 THE WITNESS: The air conditioner. 13 MR. FREEMAN: Yeah, it is. 14 BY MR. PAUL SMITH: 15 Q. Did you hear my question? 16 A. Yes; yes. 17 Q. And the answer is yes? 18 A. Yes, he was very extensively involved in that. 19 Q. But as far as you knew when you first met him, he 20 had not done work for Lilly before 1978. 21 A. I was not aware of him having done any. 22 Q. Well, did he after 1978? 23 A. Yes, he started doing studies for Lilly, doing 24 studies that I was involved in. 25 Q. All right. Were you his contact there at Lilly, 92 1 or how did the relationship with Dr. Feighner and Lilly come 2 about? 3 A. I hired him as an investigator to do clinical 4 trials. 5 Q. Was that as part of your duties as a medical 6 monitor for the clinical trials? 7 A. Yes; yes. 8 Q. What was he doing clinical trials on? 9 A. I can only remember for sure fluoxetine. I can't 10 recall the other compounds, so I can't say. 11 Q. And when did he first start doing clinical trials 12 for fluoxetine? 13 A. Approximately '79, '80. I have to not be precise 14 on the date because I can't recall. 15 I don't recall when I ran my first study out 16 there. I don't even recall the date of the first study that 17 I ran, so, I'm sorry, I'm not evading you. 18 Q. So you met him first in 1978 -- 19 A. Uh-huh. 20 Q. -- but it was 1979 or 1980 before he did any work 21 for you. 22 A. No. I probably met him within one year of him 23 doing the study for us, sometime within one year. 24 Q. What were the circumstances of your first meeting? 25 A. For me to evaluate him, see what his interests 93 1 were, to see if he had the time to do the study in a manner 2 that we wanted it run. 3 Every investigator that was hired was interviewed 4 before as opposed to after. 5 Q. How did you know of Dr. Feighner? 6 A. He had a very good reputation, very well known. 7 In particular, he had drawn up the Feighner Criteria for 8 Depression, which was the basis of the RDC and ultimately the 9 DSM-III. 10 Q. Feighner Criteria for Depression? 11 A. Uh-huh. 12 Q. And is that a rating scale of some sort? 13 A. Yes. 14 Q. Sort of like the Hamilton, HAM-D -- 15 A. That is correct. 16 Q. -- Scale? 17 A. Uh-huh. 18 Q. And what did you say that later became known as? 19 A. It was -- it was also criteria, but how many of 20 each different area a person must manifest to qualify. They 21 are very much like the DSM criteria. 22 The first scale or criterion that picked up on 23 this was RDC, Research Diagnostic Criteria. Those preceded 24 the DSM criteria. 25 Q. Okay. So you first had the RDC, the Research 94 1 Diagnostic Criteria, -- 2 A. Uh-huh. 3 Q. -- and then you had the DSM criteria. 4 A. That is correct. 5 Q. And DSM stands for --? 6 A. Something statistical methods. I don't know the 7 full name of the book. You'd have to probably tell me. I 8 don't know. 9 Q. I don't know. 10 MR. MURGATROYD: Diagnostic Statistical Methods. 11 THE WITNESS: Is it? Statistical Methods, 12 whatever. It's something you wouldn't think would be a 13 criterion thing. 14 BY MR. PAUL SMITH: 15 Q. Okay. And then Dr. Feighner had the Feighner 16 Criteria for Depression. 17 A. That was way early on before the RDC came out, 18 yes. He was quite famous, well known for that. 19 Q. When did that come out? 20 A. Preceded RDC. 21 Q. Well, is that how you knew of Dr. Feighner? 22 A. I knew of him. I also in the course of reading 23 literature found very extensive publications by him. I also, 24 of course, would speak with people, and everyone knew 25 Feighner. 95 1 It was essentially a question of, "If you can get 2 Dr. Feighner to participate, it would be a real big plus for 3 you," so I had to go and meet him and find out who he was. 4 Q. Plus in what respect? 5 A. I'd have a very competent, experienced 6 investigator. He had been doing clinical trials for the 7 industry for at least yhe twenty years, or whatever time that 8 his Feighner Research Institute was in existence. 9 Q. So did he come to Indianapolis or did you go to 10 San Diego? 11 A. I went out to San Diego. 12 Q. Did anybody with Lilly accompany you to San Diego 13 on that initial meeting? 14 A. I can't recall. 15 Q. Would there be notes or memoranda or any kind of 16 records made of that trip and that interview? 17 A. I would doubt it, but I wouldn't know so. 18 Q. If I were to look for those notes, who would I ask 19 at Lilly? 20 A. You got to remember, I left Lilly nine years ago, 21 and now you're going back fifteen, sixteen years in time, and 22 I can't tell you because I really -- I don't even know if 23 names that even flashed through my mind as I talked with you 24 this morning when I was talking; you said, "Are they still 25 there?" and I had to answer, "I don't know," unfortunately. 96 1 Q. Well, would it have been your practice to -- when 2 you interview a prospective investigator, to make some kind 3 of notation concerning that interview? 4 A. No; no. I'd either bomb him or keep him on my 5 list. If I met people -- I traveled to many sites all over 6 the country as I was starting to get together the 7 investigators for the program, and if there was any reason 8 whatsoever, you just drop it and you keep going. 9 Q. You see, you used the term "keep him on my list." 10 Did you have a list of individuals? 11 A. Mental list. 12 Q. Well, was there a -- in existence at that time in 13 1978 when you started looking for investigators some type of 14 directory or listing or group that you could go to to 15 selecting investigators for a particular area? 16 A. Primarily I used the literature and I called 17 people that I knew in the industry who had done studies of 18 their own in that area to find out if they had had good or 19 bad experiences with people and their competency, and then I 20 went to see them to sort of like, if you will, a preliminary 21 sort of thing from -- input from sources, recommendations, 22 and then following through on my own. 23 Q. All right. So the literature you would review 24 would be what? 25 A. Publications that would occur for any of the 97 1 clinical trials that had taken place with other people's 2 compounds to see what type of people were doing studies, what 3 type of studies they did. 4 Q. Where would you find that literature? Would 5 you --? 6 A. In the library. 7 Q. Lilly's library? 8 A. Yes; that's probably the only source that I used 9 to any measurable extent. 10 Q. I'm sorry, I didn't hear you. 11 A. That's probably the only one that I used to any 12 measurable extent. 13 Q. Is there a society of researchers or a society of 14 clinical investigators or an American Association of Clinical 15 Investigators? 16 A. I'm sure there are. I remember something about 17 American Society of Clinical something, but I didn't use 18 that. 19 I merely looked up their credentials in the 20 American Psychiatric Association, made sure they were board 21 certified, and to see what all I could find out about them 22 from those written sources; but primarily I'd look at their 23 papers, the type of work that they did, and I would read how 24 they did their studies. 25 Q. All right. So you needed an investigator, you 98 1 would need an investigator to investigate fluoxetine, for 2 instance; is that correct? 3 A. To conduct a clinical trial with fluoxetine or any 4 of the compounds that I used. 5 Q. And so in said in order to find an investigator 6 you would research literature. 7 A. As a source, yes. 8 Q. All right. Do you follow, Dr. Stark? What I'm 9 trying to address now is how you got to Dr. Feighner. I 10 think you told me generally that, but I'm wanting to know how 11 you would go about finding investigators. 12 You're a neuropsychologist working within a drug 13 company, you need a drug investigated, you need some clinical 14 trials done; is that correct? 15 A. Uh-huh. 16 Q. Isn't that what was happening? 17 A. Yes, in general. 18 Q. And obviously Lilly is interested in having this 19 reviewed by somebody knowledgeable in the area, I would 20 think; is that right? 21 A. How do you mean "reviewed"? I'm not sure. That's 22 a new word that came in, now. 23 Q. Okay. The clinical trials conducted by someone 24 who's knowledgeable in a particular area. 25 A. Yes. 99 1 Q. You don't want a group of gastroenterologists 2 doing a clinical trial on a neuropsychological drug, do you? 3 A. No, we would not use gastroenterologists for a 4 psychotropic drug evaluation. 5 Q. So how do you go about finding a psychotropic 6 investigator to conduct a clinical trial with respect to a 7 psychotropic drug? 8 MR. FREEMAN: I think he's answered that at least 9 three times. He searched the literature, he looked at 10 their credentials, he talked to people that had had 11 experience with them, and he interviewed them. 12 A. Now, if that wasn't clear, though, I'll be glad to 13 repeat it again, but I don't know if I made it clear. 14 Q. Well, you had talked about a list that you had, 15 and I think you said that was a mental list. 16 A. I may have written it on my desk on a piece of 17 yellow paper, too, but I don't think if there's -- if you're 18 asking do I have or had a permanent record, I did not have a 19 permanent record until such time as I had a study all laid 20 out, and then that list would have contained the people with 21 whom I was going to conduct the study. 22 Q. We'll get into that in a little more detail later. 23 A. I'm sorry? 24 Q. I said we'll get into that later in a little more 25 detail later, but right now I'm interested, did Lilly itself 100 1 have a list or some group of individuals that they already 2 knew were qualified clinical investigators? 3 A. I don't know if they did. You asked me if Lilly 4 did. 5 Q. Right. I'm talking about at the time you 6 secured --. 7 A. I did not have such a list available to me. 8 Q. Did you ask anybody -- you were working for Lilly 9 at the time, weren't you? 10 A. Yes, I was, sir. 11 Q. Did you ask anybody else at Lilly if they had a 12 group of clinical investigators that had investigated 13 neuropsychological drugs, psychotropic drugs that Lilly had 14 produced in the past? 15 A. I don't know if I did. Chances are good I 16 probably asked someone if they knew of anyone or heard of 17 someone good, to just give me their names and credentials. 18 Q. If you had asked somebody there at Lilly for this 19 information, who do you think it would have been that you 20 asked? 21 A. Probably the names that I gave you who were my 22 overseers or supervisors before. 23 Q. Dr. Zerbe? 24 A. Probably. 25 Q. Leigh Thompson? 101 1 A. Probably. 2 Q. Did I miss any? Cecil Bendush? 3 A. Yes. 4 Q. All right. Back up, Dr. Feighner (sic). 5 You flew to San Diego and met with Dr. Feighner. 6 A. Okay. 7 Q. Did Dr. Feighner have an office there in San Diego 8 which you all met at? 9 A. Yes. 10 Q. And what was laid out? What did you explain to 11 Dr. Feighner you needed? 12 A. I can't recall precisely. 13 Q. Generally. 14 A. Generally, I had to conduct a study and what it 15 was, the type of patients that we were interested in, and the 16 numbers of patients to conduct the study. Those were my 17 needs. 18 I also interviewed him as to his abilities, his 19 interests, his skills, his patient population, his staff, and 20 I also saw the facilities when I was there as well. 21 Q. How many individuals did he have on his staff at 22 that time? 23 A. I don't know. 24 Q. Well, generally. 25 A. I don't know. 102 1 Q. Well, did you know then? 2 A. No; I only knew the key people that I was 3 interested in, namely does he have a good study coordinator, 4 a good study nurse and backup staff. Those are my main 5 criteria that I look for. 6 Q. How many individuals are there now working for 7 Feighner Research International? 8 A. I don't know of any company by that name. 9 Q. Feighner Institute -- Feighner Research Institute. 10 A. I don't know. 11 Q. What is the address of International Clinical 12 Research Corporation in San Diego? 13 A. 5160 Carroll Canyon Road. 14 Q. C-A-R-R-O-L? 15 A. O-L-L. 16 Q. What is the address of Feighner Research 17 Institute? 18 A. I don't know. 19 Q. Is it in the same -- 20 A. No. 21 Q. -- location? 22 A. No. 23 Q. Did you tell me before last that Feighner Research 24 Institute does work for International -- International 25 Clinical Research Corporation? 103 1 A. Yes, I did. 2 Q. I thought both companies were research 3 corporations that did studies. 4 A. I don't think so. I guess you misunderstood. 5 Q. Okay. Why don't you explain to me what the 6 difference in those two companies is. 7 A. I think we already covered that, but I'll do it 8 one more time with you, if it will help. 9 Feighner Research Institute is a investigator -- 10 individual group of investigators who do clinical trials for 11 either pharmaceutical industry or for contract research 12 organizations. 13 International Clinical Research Corporation is a 14 clinical -- is a contract research organization, and we hire 15 on behalf of the pharmaceutical industry investigators, such 16 as Feighner Research Institute. 17 Does that help? 18 Q. Probably. 19 International Clinical Research, then, will do a 20 whole package for a particular drug company; they'll 21 coordinate the clinical trials -- 22 A. Or parts thereof. 23 Q. -- and Feighner Research Institute would provide 24 the investigators who actually do the clinical trials. 25 A. They would be one investigative site. 104 1 Q. Yeah. RCI might hire other entities. 2 A. Yes, that's correct. 3 Q. But Feighner Research Institute might be one of 4 the entities that they would hire. 5 A. That is correct. 6 Q. I believe you said International Clinical Research 7 is not now doing any work for Lilly; is that right? 8 A. That is correct. 9 Q. And haven't for the last four years? 10 A. Approximately. 11 Q. Is Feighner Research Institute doing any work for 12 Lilly at this time? 13 A. I couldn't tell you. I don't know. 14 Q. You haven't talked to Dr. Feighner about any work 15 he might be doing for Lilly. 16 A. No. I don't ask him what his businesses are. 17 This is a totally separate entity. 18 Q. But you and he are partners with a couple of other 19 individuals at International Clinical Research Corporation. 20 A. Yes, that's very true. 21 Q. And you and he -- and ICR and FRI have business 22 dealings from time to time. 23 A. Yes, everything you've said so far is absolutely 24 true. 25 Q. But it's your testimony here today, Dr. Stark, 105 1 that you don't know whether or not Feighner Research 2 Institute is conducting any clinical studies for Eli Lilly & 3 Company at this time. 4 A. I can answer you unequivocally, I have no idea. 5 Q. Do you know whether or not they have done any in 6 the past, in the last four years? 7 A. I cannot answer that either for you. 8 Q. Is Eli Lilly a company that International Clinical 9 Research Corporation from time to time solicits to do 10 business for? 11 A. Yes, indeed it is. 12 Q. Is Eli Lilly & Company a company that Feighner 13 Research Institute solicits business from? 14 A. I cannot answer you that directly. I do not know. 15 Q. What's your best judgment? 16 A. I certainly wouldn't want to give you my judgment 17 because I don't know what they think. 18 Q. Do you own any stock in Feighner Research 19 Institute? 20 A. No, I do not or did not. 21 Q. You never have is what you mean to say. 22 A. That's what the "did" was. 23 Q. But Dr. Feighner from the inception of 24 International Clinical Research Corporation has had an 25 ownership interest and owned stock in ICR. 106 1 A. Dr. Feighner did, not Feighner Research Institute, 2 though; yeah. 3 Q. Well, do you know if Feighner Research Institute 4 as a business entity or corporation owns any stock or has any 5 ownership interest in International Clinical Research 6 Corporation? 7 A. Do I know? 8 Q. Yeah. 9 A. Yes, I know. 10 Q. All right. And what's the answer? 11 A. No. 12 Q. You are the president of International Clinical 13 Research Corporation? 14 A. Yes, I am. 15 Q. What is Dr. Feighner's position? 16 A. His present position is a relatively new one, and 17 it's scientific adviser. He used to be medical director and 18 vice-president. 19 Q. Is he an officer of ICR at all now? 20 A. I'm not being wise. We've reorganized, and I'm 21 trying to remember who's on the board. I think so; I don't 22 know so, but I think so. 23 Q. If he is an officer now, what would his office be? 24 A. He's not an officer. By your question, you 25 answered it for me. 107 1 Q. He may be a director, though. 2 A. Yeah, that's the only possibility that I can think 3 of right now, and I don't know for sure. 4 Q. What is Mr. Budetti's position with ICR now? 5 A. He's executive vice-president and chief financial 6 officer. 7 Q. And Mr. Kevin Kein? 8 A. Vice-president of scientific and regulatory 9 affairs. 10 Q. What's Mr. Kein (sic) -- or is it Dr. Kein? 11 A. Dr. Keim, K-E-I-M. 12 Q. I'm sorry. 13 What's Dr. Keim's background? 14 A. He's a pharmacologist. 15 Q. Ph.D. or M.D.? 16 A. Ph.D. 17 Q. Does he have his M.D. degree? 18 A. No. 19 Q. Dr. Stark, the reason that we've requested your 20 deposition is that Eli Lilly & Company has in response to 21 interrogatories given us your name. 22 A. I'm happy. 23 MR. MURGATROYD: I'm sure you are. 24 THE WITNESS: Thank goodness for a moment of 25 levity. 108 1 BY MR. PAUL SMITH: 2 Q. Have you talked with anybody at Eli Lilly & 3 Company concerning your deposition here today? 4 A. Yes. 5 Q. Who have you talked with? 6 A. Mary Huff. 7 Q. Anybody else at Eli Lilly & Company that you've 8 discussed? 9 A. At Eli Lilly & Company, no. 10 Q. How about from anybody else? 11 A. Yes. 12 Q. Tell me about those individuals. 13 A. Two of these gentlemen right over here, Mr. 14 Freeman and Mr. -- Brunner? 15 MR. BRENNER: Brenner. 16 A. -- Brenner. I met Mr. Smith just this morning. 17 Q. When did you first talk with Ms. Huff concerning 18 this matter? 19 A. Concerning this deposition is what you're asking? 20 Q. Yeah. 21 A. Round numbers, three weeks ago, four weeks ago; I 22 don't recall exactly. I got a call and asked if I'd be 23 available. 24 Q. Three or four weeks ago when you were contacted by 25 Ms. Huff -- 109 1 A. Yes. 2 Q. -- you were not an employee of Eli Lilly & 3 Company, were you not? 4 A. No. 5 Q. And you at that time were not doing any contract 6 work with Eli Lilly -- 7 A. That is correct. 8 Q. -- at that time. 9 A. That is correct. 10 Q. What did Ms. Huff tell you -- 11 A. That she --. 12 Q. -- in that conversation? 13 A. She said that an attorney would want to take my 14 deposition and what did my calendar look like, or words of 15 that order. 16 Q. Had you met Ms. Huff prior to -- 17 A. Yes. 18 Q. -- that phone call? 19 A. Yes. 20 Q. Was Ms. Huff in the legal department with Lilly 21 when you were still an employee with Lilly? 22 A. Yes, she was. 23 Q. All right. And so you looked at your dates, your 24 calendar -- 25 A. Yes. 110 1 Q. -- and gave her some dates. 2 A. Yes. 3 Q. Any other discussions that were had when you 4 talked with Ms. Huff three weeks ago? 5 A. Yes. She was going to come down to visit, and she 6 never did. I can't remember any other secrets, though. 7 Q. Did she explain to you why you were -- your 8 deposition was being requested? 9 A. Very generally over the phone. She was going to 10 discuss that with me if she came down, and she couldn't, so 11 she told me on the phone that we would be spending one day 12 chatting about this. 13 Q. Had Ms. Huff lied to you before that? 14 A. Up until that time she had been absolutely 15 dependable. 16 Q. What did she say generally concerning the 17 substance of what was going on? 18 A. I think her conversation, and that of the others, 19 too - it was the same thing - to just answer your questions 20 in a straightforward, honest manner, and I'm attempting to do 21 precisely that, sir. 22 Q. I understand. Well, did they tell you why we had 23 requested your deposition? 24 A. The general terms that I recall was that there was 25 part of the lawsuits that were ongoing with regards to 111 1 Prozac, and that you were representing -- I don't even know 2 if it was one or more, but you were representing someone, so 3 I don't recall actually if I was told you were representing 4 one or more clients, actually. 5 Q. Have you given your deposition in connection with 6 any Prozac case before? 7 A. No, sir. 8 Q. Has there been a request by any other individuals 9 on any other occasions for you to give your deposition -- 10 A. No. 11 Q. -- in connection with Prozac? 12 A. Nope. 13 Q. You need, Dr. Stark -- you've been doing pretty 14 good, but you need to let me finish my question -- 15 A. I'm sorry. 16 Q. -- before you begin your answer. 17 A. I'm sorry, I apologize. 18 Q. I ask questions real slow, like most lawyers in 19 Texas do, so I can understand you beginning. 20 Also, my questions are pretty obvious, too. 21 A. I'm sorry, I apologize. 22 Q. You met with Mr. Freeman, Mr. Brenner and Mr. 23 Smith, Mr. Wade Smith, this morning, did you not? 24 A. Yes. 25 Q. Or did you meet with them yesterday also? 112 1 A. I met with just Mr. Brenner yesterday and Ms. 2 Huff. 3 Q. And did you go over any material with them? 4 A. No. I had a -- was given a gift packet of my 5 publications. 6 Q. All right. 7 A. That was it. 8 Q. You were given a gift packet of your publications? 9 A. Yes. 10 Q. When? 11 A. Approximately two weeks ago, three weeks ago. 12 Q. Ms. Huff sent that to you? 13 A. No; John gave it to me. 14 Q. Mr. Brenner? 15 A. Yes; when he was down, yes. 16 Q. Do you have those documents with you? 17 A. No. 18 Q. Where are they? 19 A. I gave them back after I read them again. 20 Q. Gave them back to who? 21 A. Mr. Brenner. 22 Q. How big a stack of publications was that? 23 A. Approximately that high (indicating). 24 Q. Do you have a list of what those publications 25 were? 113 1 A. Do I have a list? 2 Q. Yes. 3 A. No, I don't. 4 Q. Obviously I'd be interested in that, Dr. Stark, 5 because I'm going to be asking you, though not today, 6 shortly, things about Prozac and fluoxetine, and if you've 7 written anything concerning fluoxetine or have expressed any 8 opinions concerning fluoxetine, it would be of benefit for me 9 to know what those articles are. 10 Have you written articles concerning fluoxetine in 11 the past? 12 A. Yes, I have. 13 Q. And did you have a list of those publications? 14 A. No, I do not. 15 Q. Can you off the top of your head recite some of 16 the publications? 17 A. No, I can't. 18 Q. How would I go about finding those publications? 19 A. Library would be a good source; look under Stark, 20 P., et al. 21 Q. Do you remember the name of any of those 22 publications? 23 A. I really don't remember the titles of them. 24 You know, I have left Lilly nine years and I have 25 worked every day since. You've got to be more understanding 114 1 than you appear to be right this minute. 2 Q. Well, if I had spent a great deal of time, Dr. 3 Stark, and if I had carefully prepared a publication that was 4 going to be published for my peers, I think I would probably 5 be able to recall the title of that publication or the 6 publication in which it was published and the approximate 7 time. 8 A. I believe you; I believe you. 9 Q. But is it your testimony you can't -- you can do 10 none of that? 11 A. Oh, I can tell you the approximate time, I can 12 tell you when I wrote them. 13 Q. All right. 14 A. 1984, 1983, give or take, and they had to be 15 published within a year to two years because that's all the 16 delay is. I can't tell you the name of the journal 17 precisely, nor the title, even. 18 Q. How many articles would there have been that you 19 authored concerning fluoxetine? 20 A. I can't tell you an exact number. 21 Q. Would it be more than one? 22 A. Yes. 23 Q. Would it be more than five? 24 A. I don't know. 25 Q. Would it be more than three? 115 1 A. Can I compromise? I know it's more than two. 2 Q. You have been to law school, have you not, Dr. 3 Stark? 4 A. Yes. 5 Q. I think we developed that. 6 Why, by the way, did you go to law school? 7 A. Because at that point in time I didn't think I 8 would start my own contract research organization, I thought 9 that would be a very pleasant way to have my retirement, 10 practicing law. That was before I was ever deposed. 11 Q. I thought maybe you did it -- I thought maybe you 12 had gone to law school because you planned to be deposed. 13 Seriously, you intended to practice? 14 A. I thought very serious that would be an excellent 15 way to actually -- you can't always go live where there is a 16 pharmaceutical firm, but you can go live wherever you chose 17 to open up an office so long as you can be admitted to The 18 Bar in that state. 19 Q. Are you admitted to The Bar in any states? 20 A. Yes, sir. 21 Q. Which states? 22 A. Indiana. 23 Q. Have you applied for admission to The Bar in any 24 other states? 25 A. No, I have not. 116 1 Q. Are you still an active member of the Indiana 2 State Bar? 3 A. No, I am not. 4 Q. Okay. Are you still licensed to practice law in 5 Indiana? 6 A. To the best of my knowledge. 7 Q. Are you still paying Bar dues? 8 A. No. I got exempted from that by filing that I am 9 not presently practicing. 10 Q. Have you written articles that have been published 11 on subjects other than fluoxetine? 12 A. Yes, sir. 13 Q. Were some of those articles sent to you by Ms. 14 Huff? 15 A. Yes, by way of Mr. Brenner. They sent me 16 everything that I had published except the one that I hadn't. 17 It was the same name, P. Stark, but it wasn't mine, and they 18 also skipped an article that I had written a chapter in a 19 book on. 20 Q. What was that article? 21 A. It was on nabilone, nabilone, if you remember that 22 compound we discussed this morning. 23 Q. What chapter or in what book does that appear? 24 A. I don't recall the name of the book. It was --. 25 Q. What's the subject of the book? 117 1 A. I think the title was Marijuana and Its Analogs, 2 or something like that, and there were different groups who 3 had done research with different analogs of the compound who 4 published their experiments and their findings. 5 Q. All right. So you read those articles again. 6 A. I read the summaries. 7 Q. And did you have any other communications with Ms. 8 Huff or Mr. Brenner before yesterday? 9 A. Yes. 10 Q. Tell me about those conversations. 11 A. Ms. Huff called me about four weeks ago. We just 12 mentioned this, if you recall. 13 Q. Uh-huh. 14 MR. FREEMAN: Other than what he's earlier 15 recited? 16 MR. PAUL SMITH: Yes, I'm sorry, I meant other 17 than what you've already described to me. 18 THE WITNESS: Oh, okay. Yes, I saw Ms. Huff, oh, 19 God, I don't know, a year and a half ago. 20 MR. FREEMAN: It was not with respect to this 21 case. 22 THE WITNESS: No. He just asked me when I saw 23 Ms. Huff. 24 BY MR. PAUL SMITH: 25 Q. I'm interested, Dr. Stark, in knowing about the 118 1 conversations you've had -- 2 A. With regards to this deposition? 3 Q. -- with Eli Lilly or any Eli Lilly employees from 4 the time you were first contacted concerning giving your 5 deposition in this case up until today. 6 A. You've heard it all. 7 Q. Have you reviewed any other documents -- 8 A. No. 9 Q. -- in connection with your testimony here today 10 other than those documents sent to you by Mr. Brenner? 11 A. No, I have not. 12 Q. Now, you had conversations yesterday evening with 13 Mr. Freeman -- 14 A. Yes. 15 Q. -- and Mr. Brenner. 16 A. Mr. Brenner yesterday afternoon, not yesterday 17 evening. 18 Q. Tell me what subjects were discussed. 19 A. With whom? 20 Q. With either one. 21 A. Mr. Freeman asked me if could I get here about 22 8:00 this morning, and I told him yes. 23 Q. Did he tell you why he wanted you there at 8:00? 24 A. Just wanted to meet me and talk with me and 25 actually discuss the fact that the deposition was going to 119 1 take place and so on, and we -- I got here at a quarter after 2 8:00, and we waited for you from 8:25 on. 3 Q. Tell me about those discussions that you had with 4 Mr. Freeman this morning. 5 A. He reiterated pretty much what John Brenner had 6 said, to answer your questions forthrightly and honestly and 7 don't play games. 8 Q. Did he discuss with you possible areas of my 9 questioning? 10 A. Nope. 11 Q. Did you ask? 12 A. Nope. 13 Q. Have you talked with Dr. Feighner concerning any 14 deposition testimony he might have given in connection with 15 claims regarding Prozac? 16 A. No, I have not spoken with him about that. 17 Q. Beg your pardon? 18 A. I have not spoken with him about his deposition. 19 I didn't know that he had been deposed, as a matter of fact. 20 Q. That was going to be my next question. Did you 21 know that Dr. Feighner had given a deposition -- 22 A. No. 23 Q. -- in connection with a claim for Prozac? 24 A. No, I did not know what a deposition -- that's not 25 true. I don't know what I heard, but vaguely in the back of 120 1 my mind there was some -- there was no discussion, but I know 2 something was going on. 3 Q. How? 4 A. Because I heard him swearing about having his 5 records gone through and being Xeroxed and having to protect 6 the patient confidentiality and stuff like that. That's why 7 I knew something was going on, but I've never asked him and 8 he has never told me anything at all in any detail whatever. 9 Q. Were you there in his office when he was doing the 10 swearing? 11 A. Nope. 12 Q. Where were you and where was he at that time? 13 A. Well, it could have been at the RCI offices or at 14 some meeting together when he was telling me what was going 15 on and the imposition on his time, the office and how 16 everyone was going nuts. 17 Q. Well, were they producing records? 18 A. I believe they were trying to get Xeroxes done. 19 You know, you're asking me a question, I'm going 20 to answer you, vaguely I even -- you may have supplied people 21 or told them to get people to come in to do it and to run off 22 all the records for you, as I recall. There's a term, a word 23 when you can block out certain things. 24 MR. MURGATROYD: Redact. 25 THE WITNESS: Yeah. Thank you. 121 1 BY MR. PAUL SMITH: 2 Q. I've never heard that term, Dr. Stark. That term 3 "redaction" has never been mentioned as far as I was 4 concerned with this litigation. 5 A. I'm sorry. Neither you nor I are looking real 6 good on that one. 7 Q. Representatives of Lilly, probably you know him, 8 Dr. Noone, Mr. Michael S. Noone. 9 A. Who? 10 Q. Do you know Mr. Noone, Michael S. Noone, manager 11 of Medical Regulatory Affairs of Eli Lilly? 12 A. No. 13 Q. You don't know him? 14 A. Noone? 15 MR. MURGATROYD: N-O-O-N-E. 16 BY MR. PAUL SMITH: 17 Q. Noone, Noone? 18 A. No. 19 Q. Are you aware that there is a -- even a Department 20 of Medical Regulatory Affairs at Eli Lilly & Company? 21 A. I'm aware there was one; I assume there still is. 22 Q. Who was the manager of that department when you 23 were there? 24 A. Bruce Peck. 25 Q. Bruce Peck? 122 1 A. Yeah. I don't know if he's alive. 2 Q. We asked Lilly to identify all persons in 3 defendant's employ or formerly employed by defendant who had 4 as their primary duty the evaluation or the review of the 5 evaluation of the safety of Prozac for the treatment of 6 depression. 7 Their answer was, "No one individual had the 8 primary duty to evaluate the safety or a review of the safety 9 of Prozac for the treatment of depression. 10 The following individuals were the researchers 11 primarily responsible for conducting or reviewing preclinical 12 and clinical studies of fluoxetine," then they list Dr. L.S. 13 Lemberger, M.D., Ph.D., Dr. R.S. Schulman, M.D., Dr. I.F. 14 Bennett, M.D., Dr. I.H. Slater, Ph.D. 15 A. He's an M.D. 16 Q. He's an M.D.; Slater is an M.D.? 17 A. Yes, sir. 18 Q. P. Stark, Ph.D. -- -- 19 A. Uh-huh. 20 Q. -- that's you? 21 A. Yes, sir. 22 Q. Dr. J.F. Wernicke, M.D., Ph.D., and Dr. C.W. 23 Beasley, Jr., M.D.; and that's the reason we're here to ask 24 you some questions today, Dr. Stark. 25 A. I'm eternally grateful. 123 1 Q. Do you know if this -- if there should be anybody 2 else on this list? Let's start off by that. These are the 3 following individuals who were the researchers primarily 4 responsible for conducting or reviewing preclinical and 5 clinical studies of fluoxetine. 6 Do you know of any other individuals that should 7 be listed there? 8 A. Well, actually after my name, I don't know of 9 anyone, because I know Beasley, but I didn't know that he was 10 doing fluoxetine studies, so --. 11 Q. Do you know Wernicke? 12 A. Joe Wernicke I knew, yes. 13 Q. Did you know he was doing fluoxetine studies? 14 A. Yes, because sort of the baton went off; the baton 15 went off to him from me. 16 Q. He was your successor? 17 A. Yeah. 18 Q. Who is Slater? 19 A. He was the guy I told you I worked for for 20 eighteen years in preclinical. 21 Q. All right. Did he kind of pass the baton to you? 22 A. Yeah. 23 Q. And then you passed the baton on to Wernicke. 24 A. Yeah. 25 Q. I.F. Bennett, who is he? 124 1 A. That's Ivan Bennett, and I don't quite -- he was 2 in the department. I don't quite know where he fits into 3 the -- I don't recall the sequence between him, Schulman and 4 Slater. I can't answer you, but they were in the department. 5 Q. In what department? 6 A. Medical research group in the C & S area involved 7 with fluoxetine, but I don't know who was where. 8 Q. Do you know what Bennett was working on? 9 A. Anything to do with psychotropics while he was 10 there, but that included fluox -- fluoxetine, excuse me. 11 MR. PAUL SMITH: Let's take a break. 12 (Deposition recessed.) 13 (Deposition resumed.) 14 THE VIDEOGRAPHER: On camera. 15 BY MR. PAUL SMITH: 16 Q. Dr. Bennett preceded you, you think? 17 A. I know he preceded me, I just don't know the 18 sequence of the three who preceded me, who was one, two, 19 three type of thing as the program progressed. 20 Q. Were all of these individuals I mentioned medical 21 directors? 22 A. No. 23 Q. All right. 24 MR. FREEMAN: You mean medical monitors? 25 MR. PAUL SMITH: Monitors, I'm sorry. 125 1 THE WITNESS: Oh, yes. 2 BY MR. PAUL SMITH: 3 Q. At different times? 4 A. Yes. 5 MR. MURGATROYD: I'm sorry, I got lost. 6 THE WITNESS: No, they actually could have been 7 going on at the same time, because until Ivan left, he 8 was just on other things, but he still had a function as 9 a medical monitor in other areas, it just wasn't in 10 fluoxetine, as an example. 11 MR. MURGATROYD: I got a little mixed up. Who 12 were the medical monitors again? I'm sorry. 13 THE WITNESS: All the names he read off. 14 MR. MURGATROYD: Including yourself? 15 THE WITNESS: Yes. 16 MR. MURGATROYD: Okay. You were all medical 17 monitors -- 18 THE WITNESS: Yes. 19 MR. MURGATROYD: -- as well as involved in the 20 safety studies? 21 THE WITNESS: I'm sorry? 22 MR. MURGATROYD: As well as being involved in the 23 safety studies; as well as being involved in the -- to 24 evaluate the safety or review of the safety of Prozac. 25 MR. FREEMAN: That's what a medical monitor does. 126 1 MR. MURGATROYD: Okay. 2 THE WITNESS: Yes, safety and efficacy. 3 BY MR. PAUL SMITH: 4 Q. Okay. I'm going to repeat these names again: 5 Lemberger, Schulman, Bennett, Slater, Stark, Wernicke, 6 Beasley. 7 Can you think of anybody else that was a medical 8 monitor or was reviewing any aspects concerning the safety of 9 fluoxetine of which you are aware? 10 A. Reviewing the safety? 11 MR. FREEMAN: Now, that's a different question 12 than what the interrogatory was -- 13 THE WITNESS: It really is. Yeah, that really 14 was. 15 MR. FREEMAN: -- because he said the primary 16 people reviewing the safety were those people. 17 A. (Cont'g) I am sure the people in the regulatory 18 group must have spent considerable time as they were 19 preparing the NDA. 20 If there was a safety section in the NDA, you can 21 be assured that the regulatory people worked on it. I wasn't 22 there; I left before the NDA went in, but you know that it's 23 got to be so. 24 Q. Who was head of the regulatory group when you 25 were -- when you left? 127 1 A. I thought it was Bruce Peck. I can't remember my 2 names. You know, I'm trying to conjure up faces right now, 3 and I'm getting too many names and faces. You sort of have 4 to excuse me a bit on that one. 5 Q. All right. Where is Dr. Lemberger now? 6 A. I don't know if he's still with Lilly or not. He 7 was about to leave, but I don't know if he has. Up until 8 quite recently he was there. 9 You're not going to show it to me, I can tell. 10 MR. MURGATROYD: No, you don't get that. Some 11 things you don't get to see. 12 MR. PAUL SMITH: See, we didn't get to see your 13 publications, you don't get to see that. 14 BY MR. PAUL SMITH: 15 Q. Seriously, the last you heard, Dr. Stark, Dr. 16 Lemberger was an employee of Eli Lilly, still working at Eli 17 Lilly? 18 A. As of last fall, that was the last time I actually 19 saw him, and he was still at that time an employee. I think 20 he was getting ready, though, for retirement. 21 Q. How about Dr. Schulman? 22 A. I haven't seen, heard or talked with him since, 23 like, two months after I started into the program. 24 Q. Bennett, Dr. I.F. Bennett? 25 A. I haven't seen him in years. He's dead, isn't he? 128 1 Didn't Ivan die? I think so. 2 Q. Dr. I. Slater? 3 A. I saw him about two months ago. 4 Q. He's in Naples? 5 A. Yes; nice man. 6 Q. Dr. Wernicke, do you know where he is now? 7 A. I found out at lunch. 8 Q. He's in Houston -- 9 A. Yes. 10 Q. -- or outside of Houston? 11 A. That I don't know. All I got was Houston, because 12 they had to talk about they were going to bring him here if 13 we got together in March. 14 MR. MURGATROYD: Forcibly retire him. 15 THE WITNESS: I'm sorry? 16 MR. MURGATROYD: Forcibly retire him. 17 BY MR. PAUL SMITH: 18 Q. How about Dr. C.W. Beasley? 19 A. I don't know him. I've seen him at meetings, but 20 I don't -- I've never had an interaction with him at all. He 21 was after my time, after I left Lilly. He had to be in 22 the --. 23 Q. Let me give you another name, Ray Fuller. 24 A. Yes. 25 Q. Tell me about Ray. 129 1 A. Nice guy. 2 Q. Is he still with Lilly? 3 A. Yes. 4 Q. What is his position with Lilly now? 5 A. I don't know of his title. 6 I thought we did this this morning. 7 MR. FREEMAN: We did. 8 MR. PAUL SMITH: We did? 9 MR. FREEMAN: Yeah, sure did. 10 BY MR. PAUL SMITH: 11 Q. In two sentences tell me who he was. 12 A. He was or is? 13 Q. Is. 14 A. He is in research, I assume pharmacology, but I 15 don't know pharmacology. He's a biochemical pharmacologist. 16 Q. Should Ray Fuller be on this list as an 17 individual? 18 A. No. He was never in the clinical at all; strictly 19 preclinical and bioclinical work. 20 Q. Well --. 21 A. Probably knows more than most all of us on that 22 list, however, but that's an aside. I wish I were smart like 23 him; that's the truth. 24 MR. MURGATROYD: He did the animal studies? 25 THE WITNESS: Huh? 130 1 MR. MURGATROYD: Did he do the animal studies? 2 THE WITNESS: Yeah, yeah. 3 MR. FREEMAN: Let's have one person asking the 4 questions, please. 5 MR. MURGATROYD: I agree. I only butt in rarely. 6 (Discussion off the record.) 7 BY MR. PAUL SMITH: 8 Q. David Wong? 9 A. Yeah. 10 Q. Who is David Wong, W-O-N-G? 11 A. W-O-N-G. 12 Q. Is he still with Lilly? 13 A. I think so. I saw him at some meetings some 14 time -- I'm sure, I know he is. 15 Q. What was his position, as you understand it, the 16 last time you saw him? 17 A. I never really knew exactly. It was a 18 biochemical-type thing. It was not clinical, if that's where 19 you're leading me. That's not where he was. 20 Q. Well, did you ever do any work with Dr. Wong? 21 A. We published together based upon some of his 22 biochemical work and Ray Fuller's work and my animal work, 23 but we were both in pharmacology. I was in the basement, he 24 was on the fourth floor, and we'd bring together our data and 25 write our paper. Our interactions were such that I might see 131 1 him once every two or three weeks at lunch. 2 Does that give you a feel for our relationship? 3 Q. You weren't working on studies together or on 4 research projects together? 5 A. Individual research projects that -- where they 6 involved a common drug or working together on mechanisms and 7 so on, we would then take our data to put together to make a 8 semi-coherent story. 9 Q. What articles did you and Fuller and Wong publish 10 together? 11 A. I knew you were going to do that. 12 I don't recall the title, but I do know we have 13 one together. Actually -- yeah, we have one. I can't 14 remember if there might be two, I just can't remember, 15 because -- and I'm not ducking you. 16 When we were getting ready at our final 17 publications, David had some stuff, and I can't recall if 18 that became part of the paper or not, because it's just too 19 long. I can't follow back up for you. I know him. 20 Q. What was the subject of the article? 21 A. I can't answer you that I know. Things flip 22 through my mind, but I've got to answer you accurately, and I 23 can't answer you precisely, so I have to tell you in honesty, 24 I don't know. 25 Q. Well, did it have to do with fluoxetine? 132 1 A. Yes. That's about the only thing I think I ever 2 did a co-publication on with David. 3 Q. Do you know who invented fluoxetine? 4 A. I'm sorry? 5 Q. Do you know who invented fluoxetine? 6 A. Hasn't changed since this morning, sir. 7 Q. That is --? 8 A. I didn't know. 9 Q. You don't know. 10 MR. PAUL SMITH: Let's take a little break. 11 THE VIDEOGRAPHER: Off camera. 12 (Deposition recessed.) 13 (Deposition resumed.) 14 THE VIDEOGRAPHER: On camera. 15 BY MR. PAUL SMITH: 16 Q. Dr. Stark, can you give me a date on that article 17 that you co-authored with Drs. Wong and Fuller? 18 A. No, I can't. 19 Q. Would it have been in the '84 or '83 time span 20 that you mentioned earlier? 21 A. It would have to be prior to '84 is the only way I 22 can do it, if he was involved in the final paper that got 23 published around '85, '86, maybe, because it takes a year, 24 year and a half for an article to appear on the journal. If 25 you'll allow me the range of '82 to '86, I'm guessing we're 133 1 covering everything. 2 Q. Would this have been prior to the clinical trials? 3 A. Oh, no. No, this would be --. 4 Q. This would be after the clinical trials? 5 A. The very first one probably would have been just 6 about the beginning of; and if there was a second one, which 7 I can't recall, that would have been at the conclusion of the 8 clinical trials. 9 So if there was a second one, that would have been 10 at the conclusion that they were all done. If there was a 11 first one where we were trying to just do some animal 12 studies, it would have been work that I had done before I 13 came to the clinic but got published afterwards; so that's 14 why I'm picking that range of '82 to '86 for you. That's my 15 rationale. 16 Q. You were, while you were with Lilly, involved in 17 reviewing clinical data concerning fluoxetine in making a 18 determination or an evaluation concerning the safety of 19 fluoxetine, were you not? 20 A. No. Well, see, that's not true. It's yes/no. 21 I'm not ducking you. 22 Q. Can you explain to me why you're vacillating on 23 that? 24 A. Yes, sir. 25 As studies were completed, I would see the safety 134 1 data at the very conclusion of a study so that I remained 2 blinded as well and not know who was what or what group was 3 showing what. I did no more to evaluate the safety of a 4 compound than to be part of a committee that just overviewed 5 general -- you know, the project team that overviewed all the 6 data that were coming in and being formed and so on and said, 7 "What else do we have to do? What else do we have to do?" 8 I was not part of the regulatory component that 9 was charged with the deed of keeping track of all the safety 10 and collating it and putting it together and submitting the 11 NDA. That's why I vacillated. I was aware in general, but 12 not in particular. 13 Did I answer you? 14 Q. Maybe. 15 A. Okay. I'm trying. 16 Q. Obviously as a researcher with Eli Lilly & Company 17 you were interested in the safety of -- 18 A. Yep. 19 Q. -- all of the compounds -- 20 A. Sure. 21 Q. -- you worked on. 22 A. Yep. 23 Q. And in the clinical trials, data concerning the 24 safety of a particular compound was of importance to you. 25 A. In particular, any serious adverse event. 135 1 Q. And you in particular were concerned in your 2 studies concerning fluoxetine with respect to whether or not 3 that compound was safe. 4 A. Absolutely. 5 Q. I need for you to help me, if you can, and give me 6 a picture, because you're the first individual that we've 7 talked with, Dr. Stark, that was involved in the clinical 8 investigation of Prozac, to give me a picture of how Lilly 9 went about making this clinical investigation of Prozac. 10 You know, I'm especially concerned in the safety 11 and efficacy aspects of the drug. Do you understand what I'm 12 saying? 13 A. In general, but your question's so very broad and 14 general. If you focus a wee bit, I will try to address it 15 for you. 16 Q. I'm going to try to do that. 17 A. Okay. 18 Q. Was there a criteria set up within either the 19 project team or at Lilly, a criteria set up that would list 20 factors or items that would be of importance in -- with 21 respect to the safety of Prozac or fluoxetine? 22 A. I was not aware of any criteria that specifically 23 were set up as opposed to anything and everything. Got 24 pretty full attention. 25 Q. Well, were there any guidelines that fluoxetine 136 1 had to meet in order to fulfill a conclusion that fluoxetine 2 was safe? 3 A. I have to -- no. I have to answer your question 4 roundabout. 5 Q. That will be fine. 6 A. A serious adverse event I believe by FDA 7 definition is something that is life-threatening or the 8 unexpected and unpredicted, and therefore you really wouldn't 9 have any criteria that would say you would only pay attention 10 to something, because if it was something that was unexpected 11 or different than you had seen before and wasn't within a 12 guideline that you laid out, you wouldn't say obviously it's 13 not important, because as a matter of fact, it becomes more 14 important because it was unpredicted, unexpected; and as a 15 consequence, I don't know of any list of anything, but rather 16 as anything happened, it got listed and was addressed by 17 different functions within the corporation. 18 Q. I guess what I'm getting at is: Before you 19 started making a determination concerning safety, was any 20 thought or any attention directed as to what could Lilly do 21 to make a determination with respect to whether or not this 22 drug would be safe? 23 A. You'd have to give me an example of what it is 24 that you are saying. 25 You know, you're saying things that are not too 137 1 logical at this point in time to me. I don't want to offend 2 you, I just -- I know you must be wanting me to tell you 3 something, and I don't know for sure what it is, because, you 4 know, in doing research and going into a clinical trial, you 5 have animal data, you have phase one data and so on, and 6 everything is a normal progression. So I know you must want 7 to know something. 8 Q. Well, maybe I don't understand what the normal 9 progression is and I don't understand how this research 10 progresses, and maybe it would help if you start off by 11 giving me a general outline on how that works. 12 A. Oh, it would be a most general outline. 13 Q. That'd be fine. 14 A. One does pharmacology, one does toxicology. 15 Toxicology is relatively broad ranging, from initial acute, 16 to long-term chronic, and you must have two species in which 17 you have done two-year carcinogenesis studies. 18 Q. Slow down just a second, I'm trying to write some 19 of this down. 20 A. Okay. You have six-month and a one-year tox that 21 is done with histopathology, looking at all the organs, their 22 appearance, their body weights and so on. 23 All these things -- and this is only a brief 24 overview, because I have not covered everything because the 25 numbers of species of animals that would and would not be 138 1 involved would vary. 2 You look to see if the metabolites are 3 appropriate. As soon as you've gotten the very first human 4 study, you look to see if the metabolites are the same in 5 that man as it was in some of the animals, or is there an 6 inappropriate animals species, in which case you go look in 7 the appropriate animal species. 8 The number of people and the amount of expertise 9 brought to bear I think - and I'm not defending Lilly or 10 anything in your eyes - but is mind boggling to anyone who is 11 not in the industry, and I don't think Lilly is an exception. 12 I think all the large companies do really an outstanding job, 13 they really do, and anyone who thinks differently is not 14 aware of the limitations of the human being. That's my 15 position. 16 I'm a strong believer in good pharmacology, and I 17 think the company I worked for did well; and I now work for a 18 significant number of companies and I see a nice quality. 19 America will never be ashamed of its stuff. 20 But we -- you progress, you evolve, you get human 21 volunteers where you do very low doses, and you just look at 22 them, watch them, observe them, take bloods every hour; they 23 become essentially a pincushion. You try to learn, you make 24 sure that it corresponds. 25 You can't do anything without having an objective 139 1 observer, namely the FDA, say you may now proceed with this 2 protocol after you've even given a protocol. You have to 3 give evidence of this and of that as you progress down the 4 line. 5 You know, as I talk, you do segment one, segment 6 two, segment three where you do normal reproduction; first 7 generation, multiple generation reproduction. These where 8 all done with these compounds, so I'm having a hard time, 9 because you say did Lilly address the safety. 10 All these things were done, and this kept going on 11 and on and on. I mean, it's -- when you get to the clinical 12 trials for efficacy, you've got your safety in there. If 13 they have an ingrown toenail, you record the damn thing. The 14 pertinence to the drug is pretty darn slim, but you record, 15 you follow; these things are all listed. 16 You know, in a PDR you have the list of what 17 happened with placebo, what happened with drug, what's a 18 normal phenomenon, what's going to happen within a world 19 population just given nothing, and so these things were all 20 done. 21 So when you say to me what were the criteria, the 22 criteria were really indeed open. Anything that comes along 23 is of interest and pertinence, and the more different it was 24 than anything that was ever seen, the more important it is, 25 and that was all addressed. 140 1 Q. Maybe, I guess, my question is: Was there a game 2 plan or a procedure that is employed to determine whether or 3 not a particular compound is safe? 4 A. Yeah, to evolve --. 5 Q. Would that be a better question? 6 A. You could. It's to allow a program to evolve 7 slowly, and as the data permit, to expand and expand. 8 You have regulations from the FDA, as an example, 9 if that's where your mind is going, that you can't use women 10 of childbearing potential initially until you have 11 preliminary evidence of efficacy and until you have some 12 initial reproductive studies, so you don't even go into both 13 male and female originally by regulation, by statute that's 14 out there. 15 That's a game plan, if that's what you want, 16 because you complete that portion, have it evaluated 17 internally, then by the FDA, and then you start doing your 18 next step after that and not before that you've evolved, you 19 move on to the next step. 20 Is that a game plan? I guess so. I don't know if 21 that's what you had in mind. 22 Q. Well, let me ask you this: Was the process of 23 getting fluoxetine approved or making a determination with 24 respect to whether or not fluoxetine was a safe drug? Was 25 that process in progress when you joined Lilly in 19 -- 141 1 MR. FREEMAN: '68. 2 Q. -- 68? 3 MR. BRENNER: '63. 4 A. I joined Lilly in '63. 5 MR. FREEMAN: '63. 6 Q. '63? 7 A. I don't think fluoxetine was even a gleam in their 8 eye at that time, so I would have to answer no, there was no 9 program. They didn't -- as far as I know, fluoxetine was 10 nothing in '63. 11 Q. Where was Lilly --? 12 A. I'm afraid to say anything anymore because he's 13 checking me out. 14 Q. Where was Lilly in connection with this game plan 15 or this plan or progress when you first became aware of the 16 fluoxetine project or --? 17 A. When I became involved in fluoxetine clinically? 18 Q. Uh-huh. 19 A. Where was Lilly? Lilly at that point in time had 20 completed phase one, which involved single or multiple doses 21 in normal, healthy volunteers; that had all been done. There 22 had been some efficacy studies tried. 23 Now, you cannot have an efficacy study that does 24 not have a safety component to it. You can have a safety 25 study without any efficacy component to it, so that at any 142 1 time anyone ever tells you that anything was done with 2 regards to efficacy, you know that there's a safety component 3 to it. You can't have one without the other, but you can 4 have the safety without the efficacy. So we should always 5 know, if I do use the term loosely "efficacy," you know that 6 it includes safety. 7 That's about when I became involved. There had 8 been some studies going on. They were looking -- the dose 9 had moved extraordinarily slowly while they were looking to 10 see what was manifest. 11 Q. What do you mean "the dose had moved 12 extraordinarily slow"? 13 A. You started off, the initial work was done at 14 extraordinarily low doses. You know that there were 15 significant number of clinical trials run with patients 16 getting sixty and eighty milligrams a day who responded 17 extraordinarily well to the compound. 18 When I came on board, to the best of my knowledge, 19 the very highest dose that had ever been tried at that point 20 was thirty, and that was for a while, and so it was a very, 21 very slow process. I don't know what the interim steps were, 22 but I know that the initial -- the study immediately 23 preceding mine was a thirty for a while, dropping to twenty. 24 I don't know if they started at a quarter; I have no idea. I 25 can't recall what the very initial stuff was. I know it 143 1 wasn't a quarter; I gave you that as an example. 2 But it evolved while they were trying to evaluate 3 whether they can pick up any activity with regards to the 4 patient and the tolerability and any side effects that are 5 shown. 6 That's like a -- and back to my same thing, it's 7 an evolving game plan to show the safety. I'm merely giving 8 you various examples that actually transpired, not 9 theoretically. 10 Q. So when you first came on, it was at thirty 11 milligrams that the tests were being -- or that the drug was 12 being studied. 13 A. At that point, yes. 14 Q. But it was your understanding that it had 15 initially been studied at even lower doses than thirty 16 milligrams? 17 A. I don't know. I said I don't know where they 18 started at. 19 Q. Who would know that? 20 A. I don't know who conducted what study. You might 21 want to go to any of the investigators who preceded me. They 22 may not remember either, because you really are going back in 23 history, you truly are, and, you know, people don't remember 24 these things. 25 After you've done fifty, sixty, seventy, eighty, a 144 1 hundred protocols, you don't recall the details of the 2 protocol that you did way back then. It's not that they are 3 weak-minded. 4 Q. How many protocols did you do? 5 A. Where, when? 6 Q. On fluoxetine, total. 7 A. I don't know the exact number. 8 Q. Would it have been fifty or sixty? 9 A. No. It would have been more than ten and less 10 than thirty. You should -- well, you should know that, 11 actually. I'm sure the records are available, which they 12 weren't to me, but I'm sure they would be to you if you had 13 to know that. 14 MR. MURGATROYD: I wish. 15 BY MR. PAUL SMITH: 16 Q. Well, when was it that you started with 17 fluoxetine? Did you tell me that? You said they had 18 completed phase one, some efficacy studies had been done, 19 there had been dosages at low dosages. When you started on, 20 thirty was the highest dosages. 21 A. Yes. 22 Q. Now my question is: What -- give me a date for 23 all of that? 24 A. I can't give you a precise date, except I came 25 over to clinical roughly '78, '77. See, it was a transition 145 1 period. 2 I was doing part bench work and part clinical with 3 the nabilone in particular, because I had been involved in 4 all the basic pharmacology with that, and so I was sharing my 5 time, then I eventually shifted over full time into the 6 clinical thing. 7 So about '78, if I -- if you'll allow me a bit of 8 latitude, plus or minus. 9 Q. So that would be the approximate date that the 10 studies were in the area that you just mentioned, that is -- 11 A. Approximately. 12 Q. -- phase one had been completed, some efficacy 13 studies had been done. 14 A. Yeah. 15 Q. What was the first thing you did at that point? 16 A. I conducted a single study, a placebo controlled 17 study, to establish whether or not I thought I saw efficacy 18 or not. 19 Q. Was that done on humans? 20 A. Yes, sir, at a single site. 21 Q. Beg your pardon? 22 A. It was done at a single site so that it could be 23 very carefully and closely monitored and watched, and that 24 was essentially the beginning of the whole program. We did 25 pick up activity, we picked up good tolerability; nothing of 146 1 significance that happened in those twenty patients who got 2 drugged. 3 There were forty patients, twenty got placebo and 4 so on, and so that gave you the next, if you will, plateau of 5 confidence, that you were doing the right thing and 6 proceeding in the right way. 7 Most people doing good research are relatively 8 conservative people, not all, but most are, and I classify 9 myself among those who are conservative. 10 Q. How long did the study take? 11 A. I don't remember the length of time. 12 Q. Was it done according to a protocol? 13 A. Yes. 14 Q. Did you prepare the protocol? 15 A. Yes. 16 Q. Tell me about -- was this the first protocol you 17 had ever done? 18 A. No. 19 Q. Was it the first protocol you had ever done in 20 connection with a study of fluoxetine? 21 A. Yes. 22 Q. Tell me how you went about preparing that 23 protocol. 24 A. I based it upon other studies that I had done with 25 other compounds prior to that, based upon other protocols 147 1 that existed at Lilly, and input from the various and sundry 2 colleagues in the business who had conducted studies with 3 antidepressants, but not serotonin reuptake ones, and what 4 allowed them to follow appropriately, what presented problems 5 with regards to enrollment or following patients and so on, 6 and I tried to incorporate what I hoped was the best of 7 everything I heard from everyone I spoke to already. 8 My protocols were considered real bitches to do. 9 They were very tight. 10 Q. Take you a long time to prepare one? 11 A. A protocol or a study? 12 Q. A protocol. 13 A. Yes, but not so ordinarily long as it took a guy 14 to do it. It works out very well. 15 Q. How many hours did you spend on that first 16 protocol? 17 A. I don't know; long time. You know, you go through 18 the thing once, you go through it twice, and after you are 19 done as an individual, you have what you call protocol review 20 committees at Lilly where you have a group of some -- ranges 21 anywhere from eight to fourteen people who each one will take 22 the protocol and play devil's advocate, and either you can 23 defend what you've done or you're going to have to change it, 24 and every one of them has a different point of view. 25 I often joked, I used to give the protocol to 148 1 eight people and get back nine opinions. 2 Q. Who was on that first protocol review committee? 3 A. Oh, I have no idea. 4 Q. Can you name one? 5 A. No, because I'd guess. See, right off the bat I 6 was going to give you my friend, Ray Fuller's, name, but I 7 have no idea if he was or wasn't on the review committee. 8 Q. How about these other individuals that we've been 9 discussing that were listed in answer to interrogatory number 10 fifty, Lemberger, Schulman, Bennett, Slater, Stark, Wernicke? 11 A. Slater would have been gone, Bennett would have 12 been gone, and Schulman would have been gone from being a 13 participant in any of these things. 14 No, it would have been people different than them. 15 It would have been people from different areas who prepared 16 other protocols. It would have been someone from regulatory, 17 there's always one or two, and you keep having different 18 people on different committees. 19 So when you say to me who was on it, I don't know. 20 There's always a functional committee for every protocol 21 that's ever approved, so I'm not answering you because I 22 don't know the exact names, who to give you. 23 Q. Would Lilly make records of those committees? 24 A. I wouldn't know what they would do about protocol 25 review committee meetings. 149 1 Regular committees always have minutes of their 2 meetings all the time, but a protocol review committee, their 3 job is to just plain be devil's advocate, and the rating 4 flows and you go through each guy, what's your objection, 5 why, how, why do you think this is best; and then after you 6 have your final protocol, it then goes back to the protocol 7 review committee where every single person who was on that 8 thing has to sign off that they were now satisfied. 9 So while any individual writes his protocol, no 10 individual really runs the show. 11 Q. Well, but will Lilly have assigned a number of 12 people to a protocol review committee? 13 A. I don't know how it worked, that the protocol 14 review committees were picked. 15 Q. Will they write the names? I mean, will Protocol 16 Number 27, for instance, have a protocol review committee? 17 A. They would have had a protocol review committee, 18 but it wouldn't be like the thing would be on the protocol or 19 anything like that. I have no idea whether or not there 20 would be some sort of a paper that would say such and such a 21 protocol was reviewed by. I just don't know. 22 Q. Well, you said everybody had to sign off -- 23 A. Yes. 24 Q. -- on a protocol. 25 A. On a piece of paper. 150 1 Q. On a piece of paper? 2 A. Yeah. 3 Q. What would be the name of that piece of paper? 4 A. I don't know. 5 Q. Is there a separate working file with respect to 6 each protocol that would reflect the various drafts of the 7 protocols, the names of the committee members, the comments 8 of the committee members? 9 A. I don't know, but I wouldn't think so. 10 For instance, when I had a protocol, as it kept 11 evolving, I only kept the one that was functional at the 12 time. So that even I who was writing it, you know, I was 13 essentially having to account to everybody, I didn't even 14 keep all the old stuff. I just kept correcting it and 15 updating it, because you can imagine what would happen to a 16 desk if you kept everything you ever did and that kept being 17 revised and revised and revised. 18 Q. Did you have computers that you were working on at 19 that time? 20 A. No, I didn't. It varied; as the program went on, 21 my secretary started using one, but more as a word processor 22 than anything else. 23 We had computers all over the statistical area, 24 but that wasn't my bailiwick at all. 25 Q. What was the number of that first protocol? 151 1 A. I don't know; I don't even have a clue. I was 2 going to say one just to be a smart guy, but I have no idea 3 if there even was a protocol one. 4 Q. You wrote it? 5 A. Depends which first protocol. 6 Q. Beg your pardon? 7 A. It depends which first protocol. 8 Q. I mean, the first clinical investigation you did, 9 you wrote the protocol on that. 10 A. Yes. 11 Q. Who was the investigator on it? 12 A. Jim Bremner. 13 Q. Jim Brenner? 14 A. Bremner, B-R-E-M-N-E-R, in Olympia, Washington. 15 Q. Does Bremner, do you know if he did any other 16 studies for Lilly concerning fluoxetine? 17 A. Yes, yes; even after I left as well. 18 (Discussion off the record.) 19 BY MR. PAUL SMITH: 20 Q. And that would have been done in 1978, 21 approximately. 22 A. Eight, nine. My guess is you're probably far more 23 aware of the date than I am, if I'm going to be realistic. 24 Q. How did you get Mr. Bremner? How did you come 25 about to get Mr. Bremner? Is it B-R-E --? 152 1 A. B-R-E-M-N-E-R. 2 Q. John Bremner? 3 A. Jim, James. 4 Q. All right. How did you select him? 5 A. I don't recall. 6 See, among other sources that we have, we have 7 people who travel for Lilly all the time - and I forget what 8 their title is - who are constantly visiting with physicians, 9 investigators, and they will -- if they get the name of 10 someone who has had good experience and seems to be 11 knowledgeable and expresses an interest, they will funnel the 12 names. 13 You asked me of sources of names. 14 Q. Yeah. 15 A. That was another source of names. There were 16 people who lived in the field and spend day in and day out 17 with physicians. They have a very keen sense of a quality 18 investigator. 19 Q. Would this be the detail man? 20 A. No. I forget what they were called. I can't 21 remember. They were -- no, not the detail. 22 There was probably five of them across the whole 23 country, six across the whole country, who just visited with 24 people for experimental design and studies and involvement in 25 clinical programs or any research-type questions that arose 153 1 and stuff. There was a name for them. I can't come up with 2 it for you. 3 Q. Were they Lilly employees? 4 A. Oh, yeah, yeah, yeah, yeah, yeah. 5 Q. Do you know the names of any of those five, 6 approximately, individuals? 7 A. I remember one name, Charles Schalk. 8 Q. Spell that. 9 A. S-C-H-A-L-K, maybe, but I'm not positive. 10 Q. S-C-H -- 11 A. -- A-L-K, maybe, but I'm not positive. 12 Q. And he was a Lilly employee? 13 A. Yeah. I forget what it was. 14 Q. Did he live in Indianapolis? 15 A. No; he was on the West Coast somewhere. See, he 16 had like regions. 17 So when you say to me where did I get the names, 18 I'm trying to think of all the sources that I had funneling 19 in, and I don't know. 20 Q. Would these have been recruiters? 21 A. No; no; no. These are guys who -- there's a name 22 for them, and it was essentially to maintain the Lilly image 23 by following through on their needs and their wants with 24 regards to research, progress, problems if they were to have 25 with any; they keep you involved with antibiotics or anything 154 1 like that. 2 He wasn't necessarily a specialist in C & S, he 3 just was involved with physicians who wanted to do research 4 and could do research. Did their facilities meet the FDA 5 regulations for drug storage capacity and appropriate study 6 coordinator and stuff like that. 7 And if they got someone who they thought was 8 really very good and was very impressive, they would then 9 send that on to the appropriate medical monitor, "Here is 10 someone who has an interest and a capacity. You might want 11 to interview them." 12 And, once again, I flew to Olympia, Washington and 13 I interviewed Jim Bremner before he ever did a study for us. 14 No one ever did a study that wasn't visited, 15 chatted with, interrogated to the extent we could, and then 16 we'd ask people what they know about that person afterwards 17 to make sure that what we thought we saw was indeed fact. We 18 were very careful, we really were. 19 Q. Well, do you think Schalk put you in touch with 20 Bremner? 21 A. That's what I don't know. This is -- you see, you 22 asked me a question. The first thing is, that was one of the 23 possibilities, or else one of the other investigators that I 24 chatted with said, "Here's a guy who would be very good for 25 doing a nice, small, carefully controlled study to tell you 155 1 what you have and don't have." 2 There's certain people who can't do large studies, 3 but are really very good at evaluating a compound, whether 4 it's going to be useful or not useful; and so you -- here was 5 a relatively small study, a total of forty patients. You 6 know, that's relatively small if you have enough time to 7 enroll. 8 Most drug firms when they do pivotal studies will 9 go as high as one hundred twenty patients at some sites in a 10 given period of time, and so this is how we picked it. This 11 came the first day. 12 Q. What department would these recruiters, for use of 13 a better word, have come from? 14 A. Recruiters isn't even close to describing them, 15 so --. 16 Q. Public relations people? 17 A. No, they really weren't. They were some sort of 18 an adviser, drug -- you know, field-type layman. They 19 weren't M.D.'s, Ph.D. types. I don't know. They reported in 20 through medical always; I don't know from which group, 21 though. They didn't come through like a medical director, or 22 a vice-president would have someone handling them. I don't 23 know who it was. 24 I just met them when I went on the road, and they 25 would meet me and take me to particular people they wanted me 156 1 to meet, or if I had a need, I'd call them and say, "I'd like 2 you to take care of thus and so for me and find out and call 3 me," and they would always be available because they worked 4 within their confined areas, and they were excellent sources 5 of everything that was going on within their region. 6 Q. They were in the field. 7 A. I'm sorry? 8 Q. They were in the field. 9 A. They were in the field, yes. 10 Q. Do you now deal with people like that -- 11 A. No. 12 Q. -- to secure business from Lilly? 13 A. Oh, no. 14 Our type of organization deals with a medical 15 director, vice-president of medical affairs. Some drug firms 16 now actually have a department where they've set up to 17 actually do the work with contract research organizations, so 18 those are the people with whom we would deal. We then just 19 hire. 20 You know, our business is very different today 21 than what it was -- than when I was at Lilly. 22 Q. In what respect? 23 A. In that we represent so many drug firms. We have 24 a fair greater number of physicians we deal with, and 25 different drug firms have their own pet physicians. They 157 1 say, "You can use whomever you like so long as you use Joe, 2 Charlie and Bill," that type of thing. 3 Q. Different drug firms have their own pet 4 physicians? 5 A. Yeah, people who --, 6 Q. In what respect? 7 A. In that they have people who they know do very 8 good work and they trust their work, they trust their 9 patients, and that gives them their comfort levels; people 10 who they've known for years whose work has been published 11 extensively, that can go before the FDA and have credibility 12 because of their work having been audited over and over again 13 and looking good. 14 And so different drug firms have these people, and 15 since I deal with all the drug firms, if they have a 16 particular individual or individuals, they want me to 17 accommodate them. 18 Q. Let's go back to that first protocol. 19 A. If we must. 20 Q. Would it be helpful to you if you saw a copy of 21 that first protocol and saw a copy of the review of that 22 first summary? 23 A. Would it be helpful to me in what way; helpful to 24 me in what way? 25 Q. In talking about that first protocol. 158 1 A. Probably not. I mean, it would refresh my memory 2 as to what was written on the protocol, but the results of it 3 would not be there for me. 4 And that first one, you now know you're pushing my 5 memory back fifteen years, and I appreciate the flattery that 6 you think I would recall so readily, but I do think we have 7 to be realistic, though, too. 8 Q. Well, I need to know a little bit more about how 9 these protocols are developed. 10 You've developed, didn't you say, ten or fifteen 11 for Lilly -- 12 A. Uh-huh; uh-huh; yes. 13 Q. -- in connection with fluoxetine? 14 A. Yes, I said that. 15 Q. And I think I asked you if there was a general 16 guideline that you used to develop the protocol, and you 17 said, "Well, I would, first of all, consider the other 18 protocols that I've used in the past -- 19 A. Uh-huh. 20 Q. -- and then modify or add or delete particular 21 items for particular reasons"; is that correct? 22 A. I think that's accurate. 23 Q. Is safety something that you consider in preparing 24 a protocol? 25 A. Absolutely. 159 1 Q. What parts of the protocol have to do with safety? 2 A. Oh, geez. I can only -- you know, you're going to 3 make me pull up something now, and I can only give you some 4 factors right off the bat, okay, and you'll have to know that 5 it's not all-inclusive by any means, okay. 6 The first thing, labs come to my mind right off 7 the bat; electrocardiograms; under appropriate circumstances, 8 eye examination; chest x-rays; physical examinations 9 throughout the course; past history; medical history; 10 concomitant medication; and then as well the type of study 11 that you're doing. 12 You will then address what is a permissible and 13 what is not a permissible patient to enter. 14 Q. Why does that make a difference? 15 A. Oh, if I were starting a study and I had a patient 16 who had a propensity to seizures, I would not put them into a 17 study. 18 Q. Why? 19 A. Because if I had a compound, such as a 20 benzodiazepine, I would not be worried. If I had a compound 21 that was not a benzodiazepine, I would always pay attention 22 to it until I knew more. A benzodiazepine has anticonvulsant 23 properties. That's in essence what I'm saying. I use that 24 just as an example to you. 25 If I had a compound that I didn't know what the 160 1 effect was on blood sugar - I'm giving you a real for 2 instance now - I wouldn't allow diabetics in the study, not 3 until I knew more about what was going on. 4 See, everything -- I'm back to my old bit about 5 evolution again. The protocols do evolve. 6 Q. All right. So in selection of the patients, is 7 that what I've seen on some protocols, is the inclusion and 8 exclusion criterias? 9 A. Yes, they play a very significant role to do two 10 things: For safety; and to design a study to get you -- to 11 answer the question that you're trying to address. 12 If you exclude psychotics and you're doing a study 13 in schizophrenia, you're going to have a tough time. 14 If I'm doing an outpatient study, I would not want 15 to have depressed patients who are seriously suicidal. If 16 I'm doing an inpatient study, those are exactly the patients 17 that should be inpatients, and therefore you would include 18 them in your protocol. 19 Q. Did you include patients who were suicidal in any 20 of your studies? 21 A. I think the term that we use is "seriously 22 suicidal," and whether they are or not determines as to what 23 category they would or would not fit into. 24 Q. No, my question was: Did you include any suicidal 25 or seriously suicidal patients in any of your studies? 161 1 A. In inpatient studies one would use seriously 2 suicidal patients because those are the only patients that 3 should be hospitalized. 4 Q. So if it was an inpatient study, you would 5 include -- you did include seriously suicidal individuals. 6 A. Yes, because those should be patients who should 7 be hospitalized. 8 Q. But if it's an outpatient study --. 9 A. Then you'd put in the criteria of "serious," and 10 they should not be seriously suicidal. 11 Q. Should not be seriously suicidal. 12 A. To the best of my recollection, I had that in 13 every one of my exclusion criteria. 14 Q. So it would be, exclude seriously suicidal 15 patients. 16 A. Correct. 17 MR. FREEMAN: That were not hospitalized. 18 THE WITNESS: That's correct. 19 BY MR. PAUL SMITH: 20 Q. Well -- 21 A. That's the outpatient studies. 22 Q. -- did you put who were not hospitalized in the 23 outpatient studies? 24 A. Well, I know you have -- I'm sure you -- if you 25 don't have, you have access to all my protocols, and you know 162 1 they all spell out whether it's an outpatient study or not. 2 So you know that they're outpatient studies, and in those 3 particular protocols we spelled out. 4 Q. So there won't be any talk of hospitalization as 5 Mr. Freeman just mentioned. 6 A. I'm sorry? 7 Q. There won't be any talk of hospitalization. 8 A. If you have a hospitalization in the course of an 9 outpatient study, the odds are ninety-nine point nine percent 10 you had a patient who was a nonresponder to that drug and you 11 had merely a manifestation of their depression. I mean, not 12 every time, but ninety-nine point nine nine percent you're 13 going to lay it on, they were a nonresponder. 14 Q. One second. You've lost me, Dr. Stark; I'm sorry. 15 A. Well, you said, what happens if a patient becomes 16 hospitalized. If they are hospitalized because of their 17 suicidal ideation, the probabilities are they just did not 18 respond to the medication, because all the other parameters 19 will join them, which would indicate an exacerbation of 20 depression or nonresponse. 21 Q. You say all the other parameters would join them? 22 A. The HAM-D. No just -- you would not just see 23 suicidal ideation; you'd see other factors going up as well. 24 A HAM-D that was twenty-one at the start, you 25 know, if a suicide ideation went from a two to three, your 163 1 HAM-D would go from twenty to twenty-one. You'd be 2 hard-pressed to say that you had an exacerbation of the 3 disease. 4 But if you have a HAM-D that goes from twenty to 5 twenty-eight, twenty-nine, thirty-two, anything along those 6 lines, it's obviously not any one factor of the twenty-one 7 factors in a HAM-D, but it's a total measure of depression. 8 What we're talking about are factors of 9 depression, and that's where I want to focus your attention, 10 if I can. 11 Q. So did you consider the factors of depression in 12 drawing the protocols? 13 A. Absolutely. 14 Q. In what respect? 15 A. Well, you remember when you read it, they had to 16 have a HAM-D of at least twenty, the improvement or 17 exacerbation; they couldn't go down below twenty, nor could 18 they drop any more than twenty percent. You remember that. 19 Q. How will we determine which of these protocols are 20 your protocols? 21 A. I have no idea. 22 Q. Do they have your name on them? 23 A. I don't -- I don't know. I can't remember what's 24 on the front page. I'm trying to remember. 25 Q. See, I don't know but what one of your protocols, 164 1 Dr. Stark, might have been taken -- some other medical 2 monitor or some other individual at Lilly was evaluating 3 fluoxetine and looked at your protocol and said, "That is a 4 good protocol. I am going to use that for this study, for a 5 different study." 6 A. I can't help you. The big reason is, A: It's 7 been nine years, and probably in that period of time I've 8 worked on in excess of a hundred protocols; and I couldn't 9 even picture the cover page of a protocol when you asked me 10 if my name was on it, that's how bad it was. 11 Gee, I feel like a bad boy in the corner. You're 12 passing a lot of notes over there. 13 Q. Dr. Bremner, James Bremner, did Protocol Number 14 20, was the clinical investigator for Protocol Number 20. 15 A. Is that the first one that I did? 16 Q. Do you know --? 17 A. The number doesn't do something for me. 18 Was it a forty-patient study? Did it have placebo 19 against drug? Was it done around '78, '79? 20 Q. Let me take a break and see if I can help you. 21 A. Okay. 22 (Deposition recessed.) 23 (Videotape Two ended at 2:45 p.m.) 24 (Deposition resumed.) 25 (Videotape Three started at 3:10 p.m.) 165 1 THE VIDEOGRAPHER: On camera. 2 BY MR. PAUL SMITH: 3 Q. Bremner was your first inves --. 4 MR. FREEMAN: Just a minute, Paul, before we get 5 back on the record. 6 While we're back on the record, I wanted to inform 7 you that we have been able to arrange both with Dr. 8 Stark and with Dr. Wernicke to be here for that week of 9 the twenty -- what is it, Mary, 29th? 10 MR. MURGATROYD: You have been able to arrange 11 that? 12 MR. FREEMAN: Yes. 13 Dr. Wernicke is available only on the 31st and 14 perhaps the 1st. 15 THE WITNESS: That's Wednesday and Thursday. 16 MR. FREEMAN: And we could maybe start him on the 17 afternoon of the 30th. 18 MR. MURGATROYD: Why the afternoon? 19 MR. FREEMAN: If you can complete Dr. Stark the 20 29th and the morning of the 30th, or we can maybe begin 21 him the morning of the 31st, but he'd have to fly in 22 here the morning of the 30th is the reason I say the 23 afternoon. 24 MR. MURGATROYD: All right. And he's available 25 Wednesday and Thursday? 166 1 MR. FREEMAN: Uh-huh. 2 MR. MURGATROYD: And then Dr. Stark is available 3 Friday? 4 MR. FREEMAN: And then if we had to go over, we 5 might could go over onto the 1st; and Dr. Stark would be 6 available on the 29th and the morning of the 30th. 7 MR. MURGATROYD: How how about the 2nd if we don't 8 finish? 9 MR. FREEMAN: What about the what? 10 MR. MURGATROYD: 2nd, the Friday. 11 MR. FREEMAN: I don't think he's available then, 12 but that gives you two and a half days. 13 THE WITNESS: I don't have that much time, I 14 really don't. 15 MR. BREMNER: He's asking about Dr. Stark on 16 Friday and that's not a possibility. Dr. Stark's 17 available on Monday. 18 THE WITNESS: I don't have the time, really. 19 MR. MURGATROYD: So that we don't come Monday 20 through Friday, we come Monday through Thursday. 21 MR. FREEMAN: Well, you won't get out of here 22 probably until Friday morning, maybe. 23 MR. MURGATROYD: I'm saying that you're not going 24 to have -- I take it Wernicke is not going to be 25 available Friday morning. 167 1 MR. FREEMAN: That's what I understand -- 2 MR. MURGATROYD: So it's not like we're booked for 3 five days, it's four. 4 MR. FREEMAN: -- is we've got him two and a half 5 days for you, which I think is a pretty reasonable 6 length of time to depose any human living. 7 THE WITNESS: Even nonliving, Joe. 8 MR. MURGATROYD: You're assuming they are 9 reasonable questions. 10 MR. FREEMAN: Excuse me, I just wanted to make 11 that --. 12 MR. PAUL SMITH: And I appreciate -- Dr. Stark, we 13 do appreciate you making yourself available again, and 14 counsel, we appreciate you working with us on Dr. 15 Wernicke. 16 Again, as I had advised you earlier, I have a case 17 set March 29 that I've already been told is the number 18 one case. Hopefully it will be --. 19 MR. FREEMAN: If that goes forward, we will set it 20 another week. 21 MR. PAUL SMITH: Right. Hopefully we'll be able 22 to get that settled. 23 THE WITNESS: I don't even get back here until the 24 Saturday before, actually. 25 MR. PAUL SMITH: All right. 168 1 BY MR. PAUL SMITH: 2 Q. Dr. Stark, you said that Mr. Bremner -- Dr. 3 Bremner was your first investigator that did your first 4 study, the 20/20 study. 5 A. Whatever the protocol number is. I don't know the 6 protocol number. 7 Q. I understand. Who was the next investigator that 8 you hired? 9 A. Blank. You remember your first baby. I don't 10 remember, I truly --. 11 MR. MURGATROYD: Don't remember your second baby? 12 THE WITNESS: Don't let my middle daughter hear 13 that. 14 I just -- I don't, I really -- you know what I 15 don't even know, is whether there were a series of 16 two three studies or one second study or not. I just 17 don't remember the sequence of what happened back there. 18 BY MR. PAUL SMITH: 19 Q. Well, did you use Dr. Baron Shopsin? 20 A. I used Baron Shopsin from New York. 21 Q. Would he have been shortly after Bremner? 22 A. I don't know. I don't know the sequence. I 23 can't -- I can't conjure up the sequence in my mind anymore. 24 Q. Was Dr. Shopsin an investigator that you did or 25 used for another study using another protocol? 169 1 A. I can't tell you whether I used Baron Shopsin for 2 fluoxetine or another compound. I have done studies with 3 Baron Shopsin, but you see that is -- right now I can't 4 separate out my protocols anymore. They are all mixed up in 5 my head. 6 Q. How about Dr. Howard Masco? 7 A. Yes, and I know that I used him in fluoxetine. 8 I've used him in other things, too, but I remember him for 9 fluoxetine. 10 Q. Do you remember what he did for you in connection 11 with studying fluoxetine? 12 A. I don't remember what protocol he did, but I 13 remember he did have something very unique. 14 He had some patients who were on for as long as 15 five years, and we were able to track patients for 16 extraordinary, prolonged periods. It was no big numbers. As 17 you can imagine, the attrition rate as studies go on, the 18 attrition rate is enormous, but we were able to draw blood 19 samples from some patients. 20 We flew a crew down here where we accumulated 21 everybody who's left in his study, and he still had six, 22 seven, eight, nine patients that Lilly was able to give to 23 the FDA data on some patients who were as long as five years. 24 That's why I remember him, he was unique. 25 Q. Was that while you were still with Lilly, when 170 1 that study was completed after five or six years? 2 A. He -- the study was -- he just had open-labeled 3 patients still running. I was still there then. 4 Q. Where is Dr. Masco? 5 A. Now? 6 Q. Or where was he when he did the studies? 7 A. Somewhere outside of Tampa. It wasn't Tampa, but 8 it was in that area; something along the beach there. 9 MR. MURGATROYD: Clearwater? 10 THE WITNESS: Pardon me? 11 MR. MURGATROYD: Clearwater? 12 THE WITNESS: No. More -- (indicating). 13 BY MR. PAUL SMITH: 14 Q. Dr. Feighner, of course, did studies. 15 A. Yes. 16 Q. How about Dr. Harold Goldberg, did he do any 17 studies for you? 18 A. Yeah, but I don't remember on what compound. 19 Finnerty (phonetic spelling), Goldberg, they are 20 in the Boston area, or were; I don't know if they still are. 21 Q. What did you say, Goldberg? 22 A. Finnerty and Goldberg, they were two guys. When 23 you say "Goldberg," Finnerty went with it. 24 Finnerty was his business manager, and Goldberg 25 was the psychiatrist; so when you gave me one, you gave me 171 1 the other. 2 Q. They were always a pair? 3 A. Yes. 4 Q. You couldn't talk to Dr. Goldberg without talking 5 to his business manager. 6 A. Yes, I could, I could; but I -- what can I say, 7 you triggered my mind. 8 Q. How were these investigators paid? 9 A. By check. 10 No. I'm not sure what you mean. You have to help 11 me. 12 Q. Were they paid by study, by patient, by time, by 13 project? 14 A. By patient, by visit. 15 Q. They were paid a certain amount per patient per 16 visit. 17 A. Correct. 18 Q. Do you recall how much it was? 19 A. No; and I know, just for your information, it 20 varied from investigator to investigator, which would also 21 vary by the region and the cost of living and so on and doing 22 business and so on. These were part of the criteria that 23 went in. 24 Q. Part of the criteria that went in? 25 A. Yes, besides the -- depending on how much you 172 1 wanted a particular person, and if he said, "I had to have" - 2 I'll make up a number for you - "fifty dollars more than 3 Joe," I decided I was willing to spend my fifty dollars to 4 have him in the study because he was such a good person to 5 have. 6 Q. From your understanding, this was uniform 7 throughout all the clinical investigators, that they were 8 paid on a per patient basis. 9 A. Yes. 10 MR. FREEMAN: Per patient, per visit. 11 A. (Cont'g) Per patient, per visit. 12 At one time payments used to be just per patient, 13 at the very, very beginning, and it was very, very difficult 14 then to reimburse fairly. 15 Some patients would stay in long, some would stay 16 in short, and so you had your choice. You could give a 17 person an average amount of money, but the guy who had a 18 patient stay in for a long time or for any particular reason 19 had them stay, he was putting in so much more time as 20 compared to Investigator B or A that he really wasn't getting 21 paid for the time. 22 So the fairest thing was that every patient, 23 whatever time they are in, it's just as if you had an office 24 visit, you got paid for each of the office visits, so to 25 speak. 173 1 Q. Well, a lot of these individuals who were being 2 studied, the investigators had them as patients anyway 3 already, did they not? 4 A. Some did, yes. 5 Q. And -- 6 A. You dropped something. 7 Q. -- they were being charged by the physician, by 8 the investigator, for the treatment they were receiving from 9 that physician. 10 A. No; no; no -- 11 Q. All right. 12 A. -- no; no. 13 The patients did not pay for their visits or their 14 medications or their labs or anything. That was something 15 that they got as a participant, if you will, for advancing 16 new medical science and knowledge. It was an incentive for 17 why they would feel good for getting some additional 18 treatment, particularly some who had responded, but not 19 responded well. 20 I don't know if you've spent much time talking 21 with depressed patients or not. I tried to learn a lot by 22 spending time at some sites when they actually were 23 interviewing patients, and, you know, "How good do you feel" 24 is a very, very broad range in gamut, and patients who are 25 depressed have been depressed for -- in many cases for very 174 1 prolonged periods of time, and while they may feel better on 2 the medication, they will know and they will tell you they 3 never really feel quite good. 4 And so if there is an opportunity to indeed feel 5 as they used to feel, they are extraordinarily eager to try 6 to see if indeed there is a medication that won't just leave 7 them feeling very depressed, but actually feeling good. 8 And so this was their medication, their medical 9 care, the labs, the EKG's and so on, and the physicians could 10 not charge them for it, so the physicians got reimbursed by 11 Eli Lilly & Company. 12 Q. Would these physicians use as patients to be the 13 subject of the investigation existing patients that they had, 14 or would they go out and recruit new patients? 15 A. Both, both. 16 Q. And so if they had an existing patient for whom 17 they had been charging -- 18 A. Yes. 19 Q. -- they would advise the patient that, "You're 20 part of a study that I'm running or participating in, you're 21 participating in the study, and as a consequence, among other 22 things, you will no longer pay me the normal office visit 23 that you had been in the past." 24 A. I don't know quite the verbalization of that, but 25 I can give you an alternative scenario, if you will. 175 1 Q. All right. Please. 2 A. I don't know why I knew you'd say that. 3 There are entrance criteria that are spelled out 4 and not the least of which is that the Hamilton Depression 5 Scale must be at least twenty, and that is indeed a 6 moderately depressed -- that's not a mildly depressed 7 patient, that's a very -- that's a moderately depressed 8 patient, it's not the severe type; and the patient would have 9 to be at that level while -- let's assume you were the 10 psychiatrist, while visiting you and while treating them, 11 that's the best that they could do, because, otherwise, they 12 couldn't enter the study if they weren't at that level of 13 depression. 14 So you would then offer to that person an 15 opportunity to participate because, especially early on, 16 these were about seven-week studies, one plus six, the 17 long-term humanitarian protocols where responders were 18 allowed to continue so long as the physician thought it was 19 in their best interest to do so. 20 So while they were paying, these were patients who 21 were quite depressed, and so they were told if they would 22 like to participate to see if indeed this type of 23 treatment -- you got to remember, too, that Prozac/fluoxetine 24 at that time was a novel means of therapy. There was some 25 others around at that time that were not at the level. 176 1 Zimelidine was just being pulled off the market - that was a 2 serotonin reuptake inhibitor - because of the zimelidine 3 syndrome, the flu-like syndromes, stiff joints, cold and 4 flu-like things, so that was coming off the market. 5 For patients who had nothing else but tricyclics, 6 there was at that time citalopram, fluvoxamine, and that. 7 This was indeed -- you know, it's like penicillin, and so 8 therefore these patients were indeed offered an opportunity. 9 That's how it happened. 10 It wasn't as if, "If you come on the study, I tell 11 you what I'm going to do." If you remember the old Texaco 12 ad, "You won't have to pay me." That was not it. 13 This was really a very nice thing, and the 14 physicians very carefully picked and chose patients who they 15 thought could have an opportunity to have a different 16 treatment than what they had not been getting before. 17 So I have to put it into perspective for you. I 18 don't know if I needed to, I felt I had to. 19 Q. Well, I appreciate that. 20 A. Okay. 21 Q. Consequently, those investigators who studied more 22 patients over a longer period of time would be paid more for 23 their work than those who did see only a few patients over a 24 short period of time. 25 A. They would receive more reimbursement. 177 1 Q. Did you use Dr. Karl Rickels as an investigator 2 for any of your studies? 3 A. Yes, but I don't know which drug. 4 Q. How about Dr. Guy Chouinard? 5 A. Gee Chouinard. 6 Q. Gee Chouinard. 7 A. Chouinard, yes, up in Montreal, Neurological 8 Institute. 9 Q. Did you use him? 10 A. Yes, I did. 11 Q. For fluoxetine? 12 A. Yes, I do remember him particularly. 13 Q. How about Dr. Rickels; where is Dr. Rickels, or 14 where was he at that time? 15 A. Well, he was at the University of Pennsylvania. 16 Last I had heard he's still was there, but I wouldn't want to 17 say for sure. That's the last I heard, let's put it that 18 way. 19 Q. How about Dr. F.S. Abuzzahab, A-B-U-Z-Z-A-H-A-B? 20 A. Like Abuzzahab in Minneapolis, Minnesota. 21 Q. Let me give the court reporter the spelling on 22 that. 23 A. I'm sorry? 24 Q. Let me give the court reporter the spelling on 25 that. A-B-U-Z-Z-A-H-A-B. 178 1 And -- . 2 A. I don't know what studies Abuzzahab participated, 3 and I have used him. 4 Q. And you said he was where? 5 A. I thought Minneapolis, Minnesota, unless I've 6 really blown it all. 7 Q. And if you had used Dr. Abuzzahab -- 8 A. Abuzzahab, yes. 9 Q. -- for fluoxetine, would that have been with 10 respect to a protocol you had prepared? 11 A. If I had used him, it would have been a protocol 12 that I had prepared. 13 Q. Would that be true with respect to my -- to 14 answering all of these questions concerning these physicians; 15 if they had been one of your investigators that you had used 16 in clinical studies, they would have been using a protocol 17 prepared by you? 18 A. That is -- to the best of my recollection. You 19 all of a sudden made me nervous. To the best of my 20 recollection, yes. 21 Q. How about Dr. J.B. Cohn, C-O-H-N? 22 A. Cohn; Cohn in California? 23 Q. Yes. 24 A. Yes. 25 Q. You've used Dr. Cohn? 179 1 A. I have used him and -- I know I used him in 2 fluoxetine, besides other stuff. 3 Q. And where in California is Dr. Cohn? 4 A. Newport Beach is where I had seen him. He has 5 offices up north somewhere now as well, but at the time I 6 used to go to the Newport Beach office; just get off the 7 interstate. 8 Q. How about Dr. David L. Dunner? 9 A. Yes; Seattle, Washington. 10 Q. You used him for fluoxetine? 11 A. I can't answer for sure to your question. I've 12 done studies with David. 13 Q. How about Dr. Bernard I. Grosser, G-R-O-S-S-E-R? 14 A. Bernie Grosser; Salt Lake City, Utah. Yes, he did 15 fluoxetine. 16 Q. Have we mentioned Burton -- no, we have not. Dr. 17 Burton Goldstein? 18 A. Yes; he's down -- I used him, but I don't remember 19 what drug, and he's in Miami, Florida. He was in Miami, 20 Florida; I don't know if he still is. 21 Q. How about Dr. John Davis? 22 A. I used him; in Chicago. 23 Q. Did you use him for fluoxetine? 24 A. Yes. 25 Q. You're smiling about Dr. Davis. 180 1 A. Well, Dr. Davis has a bibliography of some -- at 2 that time, at that time, it was seven or eight hundred 3 publications. He was very world renown, and I really wanted 4 him to be able to present the paper from a group, and his 5 contribution was a very minimal number of patients relative 6 to the group he was with. 7 He did a study with two other people, I can't 8 conjure up their names for you right now, but the three of 9 them together did a study, and so I laughed, because he stuck 10 his chest out further than any of the other two investigators 11 who did three times the work that he did; so I laughed when I 12 thought of John Davis. 13 Q. You used him for punch. 14 A. Well, I just wanted him to be able to present, 15 because he presents very well, and so I wanted him to take 16 the sum paper and present their collaborative effort. 17 There were three of them that collaborated in one 18 study. I don't remember the protocol, but I know there were 19 three investigators, and John Davis was one. 20 Q. You say he presented a paper? 21 A. Yes. 22 Q. At some --. 23 A. No; no. As a matter of fact, he spoke of it at 24 Montecatini is what it was that he spoke of it. 25 Q. He spoke of it at Montecatini? 181 1 A. Yes, where we had the gathering of the 2 psychiatrists where everyone exchanged ideas. 3 Don't you -- you know about the meeting at 4 Montecatini. 5 Q. No, I don't. 6 A. Oh, sure you do. 7 Q. Dr. Stark, you're the first bigwig we've talked 8 to. We've just been talking to -- 9 A. Oh, I'm no bigwig. 10 Q. -- Lilly -- we've just been talking to Lilly 11 functionaries. 12 A. We had a symposium in Montecatini where we got 13 people together to discuss and talk about the studies that 14 had been done and had preceded the symposium at the CINP in 15 Florence. They are just twenty miles part, so we proceeded 16 there, Montecatini. 17 MR. MURGATROYD: Montecatini? 18 THE WITNESS: Montecatini. 19 BY MR. PAUL SMITH: 20 Q. Spell that. 21 A. I can't. 22 MR. MURGATROYD: What country? 23 THE WITNESS: Italy; it's about twenty miles from 24 Florence, Italy. 25 The CINP, the Collegiate International 182 1 Neuropsychopharmacology met there in 1984, and so 2 together this was like a satellite meeting. 3 BY MR. PAUL SMITH: 4 Q. And there were papers presented by Dr. Davis? 5 A. No. He spoke of it -- when you mentioned it, he 6 didn't give the paper, he gave the talk on it; but he has 7 published on it, I'm sure. Knowing John Davis, there is 8 nothing he will not publish on. 9 Q. But was this symposium in Monte -- 10 A. Catini. 11 Q. -- catini -- 12 A. Catini. 13 Q. -- was there some publication made in connection 14 with the symposium? 15 A. Yes, there was. 16 Q. And where was it published? 17 A. I don't know the name of the journal, but my name 18 is on two of the papers; and if you can pick up a publication 19 of 1985, that journal is it, because it came out about a year 20 and a half after I left Lilly. 21 Q. What was your publication; I mean, what did you 22 publish on? 23 A. I gave a paper where I put together a -- all the 24 pivotal trials into a single presentation of all the patients 25 who were on placebo, imipramine and fluoxetine, as well as 183 1 the pharmacologic profiles. I believe David Hardison is on 2 it. 3 Oh, you missed one of my better papers. 4 MR. MURGATROYD: Did you have any co-authors? 5 THE WITNESS: David Hardison was in on those. 6 BY MR. PAUL SMITH: 7 Q. Hartison, H-A-R-T-I-S-O-N (sic)? 8 A. H-A-R-D-I-S-O-N. 9 Those were two of my really better papers. I feel 10 badly. 11 Q. How about in the Journal of Clinical Psychiatry, 12 March 1985? 13 A. That should be the right time, so I believe it. 14 Q. Let me show it to you. 15 A. That's got David and myself on there, David 16 Hardison and myself? 17 Q. Yeah, Paul Stark, Ph.D. and C. David Hardison, 18 Ph.D. 19 A. Yeah. 20 Q. Why don't you look at it. 21 A. Yeah. Thank you. 22 Q. Was that --? 23 A. There was another one that came out together with 24 that, which was the pharmacologic profile of that, two papers 25 side by side. 184 1 Q. It's referred to in that article, isn't it? 2 A. I have to check. 3 Q. You make reference I believe to it. 4 A. I got to check. 5 Yes. Well, the two of them were in the same 6 journal, same time. 7 Q. And that actually was presented at this symposium 8 in Monte -- 9 A. Montecatini. 10 Q. Montecatini? 11 A. Yes. 12 It was also presented in modified form at the CINP 13 one at Florence three days later. See, I learned how to do 14 it first in Montecatini, then I did a good job in Florence. 15 I'm sorry, I really thought you knew about that. 16 Q. No, I didn't. I hate to confess my ignorance. 17 A. Oh, please, come on. 18 Q. Was this a symposium where 19 neuropsychopharmacologists met and discussed the various 20 developments? 21 A. This was primarily -- the Montecatini meeting was 22 primarily a symposium, get-together of practicing 23 psychiatrists worldwide. It was set up to be a pseudo 24 critique of the studies that had been done to question, to 25 present, and essentially share the data. 185 1 It was a nice, wide open, wide ranging type of 2 thing. Very significant questions came up and so on. These 3 were people who really had no vested interest, but were doing 4 other studies and so on, and they were there to --. 5 Q. Did it have to do exclusively with fluoxetine? 6 A. That one in Montecatini did. The one at CINP in 7 Florence was part of all the whole program, the CINP 8 meetings. 9 Q. Was this symposium in Montecatini sponsored by 10 Lilly? 11 A. Yes. 12 Q. Yes? 13 A. Yes, I truly believe it was. 14 Q. And were there audio and videotapes made of the 15 presentations there at that symposium? 16 A. I don't know about audio, but I know there weren't 17 video, because I've never had to sit up with my neck up so 18 high for so long before in my life. 19 Don't laugh. 20 Q. Was there -- do you remember standing up during 21 your presentation? 22 A. Do I recall standing up? 23 Q. Yes. 24 A. I recall standing up twice, as a matter of fact. 25 Q. All right. And were you -- do you have a 186 1 recollection now that what you were saying was being 2 recorded? 3 A. No. It was just a speaker, but whether it went to 4 a recording device or not, I don't know. 5 Q. And --. 6 A. It was no different than any other presentation 7 I've ever made, it was just the microphone and thing. If it 8 went to a recorder, I don't know. 9 Q. Did you -- was there a pre-printed publication or 10 handout? Like when we go to a legal seminar -- 11 A. No. 12 Q. -- we'll get a binder possibly of material. 13 A. I said no, and all of a sudden, I don't know, 14 that's a more accurate statement, because all of a sudden 15 when you started describing that, I don't know if there were 16 summaries of the paper handed out or not. I cannot answer 17 you. I'm sorry, it just -- I can't. 18 Q. Would Lilly have had somebody there that was in 19 charge of that program? 20 A. You know, I want to say yes, but I don't know who, 21 you know, because it doesn't make sense that all the people 22 would just turn up with no one there is the reason why I say 23 that. 24 Q. Everybody needs a leader, don't they? 25 A. Somewhere there has to be someone that said, 187 1 "Dinner is served." I don't know. 2 Q. Who introduced you? 3 A. Who was the chairperson? 4 Q. Yes. 5 A. I don't recall. 6 Q. Who was the medical director at that time? 7 MR. FREEMAN: Of Lilly Research Laboratories? 8 MR. PAUL SMITH: Yes. 9 A. I can't tell you; I just don't remember. It's 10 embarrassing, but I don't remember. 11 Q. How long did this symposium last; three days? 12 A. Oh, no. It was a one-and-a-half-day affair, and 13 we just moved on from there to CINP. 14 At all general-type meetings of certainly some of 15 the major societies, they have satellite meetings, and we 16 tried to have this as satellite because you really can't talk 17 too long about any one product at a given group meeting where 18 you have everyone who wants to have their minute in the 19 sunshine. 20 So these satellite things are very common things 21 where a given area of interest, a given compound or so on 22 gets more than one minute in the sunlight; that's really what 23 it boils down to. 24 This group was picked to actually hear and to 25 criticize, and there were criticisms, you know, questions 188 1 raised, how'd you do this or why'd you do that. It was a 2 nice meeting, it was a good one. 3 Q. Approximately how many individuals from Lilly 4 participated in this meeting? 5 MR. FREEMAN: In terms of being on the program? 6 MR. PAUL SMITH: Yeah. 7 A. Being on the program, fewer than five and more 8 than one. 9 Q. How about in organizing the symposium, is there 10 somebody there at Lilly whose job function it is to direct 11 continuing education and organize programs of this nature? 12 A. I don't even remember how this even came about. 13 You know, as I talk with you, I try to conjure up 14 so I can contribute something to you, and I really can't. 15 You know, everything you say makes absolute sense, but I 16 can't answer you to say yes to you. 17 Q. Who else was on the program with you? Dr. Davis. 18 A. No, he was not on the panel there. 19 The pivotal studies is -- those guys were all on 20 the program, and Charlie Fish was there, who gave the 21 cardiovascular part. 22 Q. Who is Charlie Fish? 23 A. Charlie Fish -- Charles Fish is a cardiologist who 24 is head of the Crannard (phonetic spelling) Heart Institute 25 who was given all the cardiovascular data in a blinded 189 1 manner, all the electrocardiograms and so on, the concomitant 2 meds, the age, weight and sex, that's it, and was then 3 supposed to separate out anything that was any significant 4 changes in the electrocardiograms of any and all the patients 5 who were on, and he presented those data after we gave him 6 what drug was which after the analyses were done. 7 Q. Sounds fascinating, this review, all those EKG's. 8 A. You don't know Charlie Fish, I do. He loves it. 9 To him it's the greatest joy in the world, to spend a whole 10 evening at home reading electrocardiograms. You don't know 11 how true you are. 12 Q. You mentioned everybody that had done the pivotal 13 studies was there. 14 A. That's all that sticks in my mind with regards to 15 the presenters. I know there had to be more, but I can't 16 tell you who they were. 17 Q. Now, at that time were there pivotal studies and 18 nonpivotal studies? 19 A. Oh, sure. 20 Q. All right. How did you all go about deciding 21 which were going to be the pivotal and which were going to be 22 the nonpivotal? 23 A. You don't decide, that's decided for you by the 24 FDA. 25 Q. All right. Well, how does -- how did a 190 1 particular study become pivotal versus nonpivotal? 2 A. Well, right off the bat, the most obvious criteria 3 is you must have a placebo group in it. 4 Q. But all of your studies had a placebo group in it, 5 didn't they? 6 A. Well, in the bipolar versus monopolar we didn't; 7 we just compared the two to see if there was a difference in 8 response. That came to my mind right off the bat when I was 9 talking to you. 10 You have to have a very uniform patient population 11 so that you can say, this, this and this were all run in 12 identical manner, therefore, they all must stand up to the 13 same criteria and scrutiny, what was or was not statistically 14 significant. 15 If you have a little bit different population here 16 and a little bit different population there, it's that old 17 expression you can't compare apples and oranges type of 18 thing. 19 So you have to delegate before, not after. This, 20 this, this, this and this will be my pivotal studies, and you 21 hang your hat and you go. You can't look at it 22 retrospectively and say that one, that one and that one will 23 be my pivotal studies. I mean, that would be great. 24 Q. Okay. But do I understand you that you designate 25 as you go in which studies you want to be --? 191 1 A. Before you start. 2 Q. Before you would do the protocol? 3 A. No. The protocol's written, and before you start 4 the study, before you pick the investigators, you decide you, 5 you, you, you and you are doing this protocol. 6 Every one of them is identical. They have 7 different numbers, but they are identical. The commas have 8 to be even exactly the same. That is where you're hanging 9 your hat on your pivotals. 10 In other words, you're not allowed to pick the 11 best ones and go, and the reason why I'm saying this now is 12 because we had one study that was so outstanding, we had to 13 throw it out - true. 14 Code, I mean, you talk about an irony of ironies, 15 throwing out an outstanding study; it drove me out of my 16 mind. 17 Q. Maybe I misunderstood, but what you're telling me 18 is, is that you design a protocol -- 19 A. Yes. 20 Q. -- and you're going to conduct a study -- 21 A. Yes. 22 Q. -- and at that point before you conduct the study, 23 you, Lilly, delegates or designates that study as a pivotal 24 study. 25 A. That's correct. 192 1 Q. And then -- 2 A. You start. 3 Q. -- do you start. 4 A. Then you start them. 5 Q. Whether it's a pivotal or nonpivotal study is not 6 something that's designated by the FDA -- 7 A. No, no. 8 Q. -- after the study is completed? 9 A. No; no; no. They designate what has to be 10 included so that the proper design can take place. 11 Q. All right. 12 A. In other words, you can do a great study comparing 13 fluoxetine to imipramine - I'm pulling that as an example - 14 just a two-arm study, and it can be fabulous - no placebo 15 arm, no pivotal, don't even talk about it, please, it's just 16 safety. I mean, the FDA just says it, period. They don't 17 want to argue, they don't want to talk, so you design 18 accordingly to meeting the regulations as well because it's 19 only fair. 20 You know, if you want to indeed know not only 21 whether a compound is efficacious, but, you know, you were 22 harping before a little bit --. 23 Q. Oh, I wasn't harping at all, Doctor. 24 A. No, you didn't harp, you raised the question. 25 Q. That's merely a characterization that Mr. Freeman 193 1 has put into your mind. 2 A. No, no, no. You raised a question significantly 3 about safety and stuff like that. 4 You know, it's not just placebo for efficacy, but 5 placebo really tells you a lot about safety, and so you 6 really do have to have it. 7 It's very difficult when you have severe illnesses 8 to justify to patients why they have to have a placebo arm, 9 and schizophrenia is one of the things that comes to my mind 10 right off the bat, because the placebo response rate in 11 schizophrenia is very low. 12 The placebo response rate in depression or anxiety 13 is quite measurable, and that's very important to how you 14 treat your patient, because if indeed they can be treated 15 without any medication, chemical treatment, then that's very 16 important for the physician to know, and indeed they deal 17 with it accordingly, but it's very difficult. 18 I'm doing a study right now in obsessive 19 compulsive behavior in children, and it has to have a placebo 20 arm because the FDA mandated it. Well, if you were a parent, 21 how would you feel about your child having an obsessive 22 compulsive disorder and having a chance of getting placebo. 23 You'd say, "To hell with it. I know what drugs are on the 24 market, I'll treat my child accordingly. Thank you." 25 So these are very tough nuts to crack, but they 194 1 are very pertinent to what you just raised. 2 Q. Maybe -- I don't understand why that a placebo arm 3 of a study can have a significant -- you can draw a 4 significant conclusion considering the safety of a particular 5 compound. 6 A. Because if you really want to know -- good example 7 with fluoxetine, what is the instance of diarrhea, okay, or 8 upset stomach type of thing. Does eighteen percent mean -- I 9 have no idea where the number came from. Does eighteen 10 percent mean something? Well, if the placebo group had three 11 percent, it probably darn well does. You now have something 12 that you say, "This is what the drug seems to do." 13 If it's seventeen percent, eighteen, seventeen 14 percent is nothing. That's very important to know because 15 now you know how different it is and what happens day-in, 16 day-out routinely just to a normal person just sitting here; 17 that's why. 18 Q. All right, sir. Now back to the pivotal/ 19 nonpivotal studies. 20 A. Okay. 21 Q. I need to get this clear in my mind. 22 A pivotal versus a nonpivotal study -- 23 A. Yes. 24 Q. -- has to do with whether or not the study was as 25 originally designed, designed in accordance with FDA 195 1 specifications and regulations concerning pivotal studies. 2 A. That is one of the aspects of it. 3 Q. And Lilly or any drug manufacturer has to 4 designate a particular study as pivotal before they conduct 5 the trials in accordance with the clinical studies? 6 A. They have to have their mind cleared what is in 7 there that will fit within the confines of the claim, okay. 8 If you've had -- an example, a good example, if 9 you've done a study that works very well in anxiety, but as 10 well takes care of the depressive aspects, let's say, of the 11 Hamilton Anxiety Scale, or conversely, a compound that works 12 in depression, but takes care of the anxiety component of the 13 HAM-D, that cannot and will not be a pivotal study. You have 14 to have the exact appropriate population with the exact 15 appropriate criteria and so on. 16 So you really very carefully design your pivotal 17 studies to answer anything that an advisory panel for the 18 most part will rightfully raise at the hearings. 19 Q. But the FDA does not look at a completed clinical 20 study and say, "Okay. This we will consider as a pivotal 21 study"? 22 A. No. You will say, "I have designated these as my 23 pivotal studies," and if you don't have an appropriate 24 population, an appropriate criteria, such as the placebo arm 25 and so on, the FDA will say, "These are not part of the 196 1 pivotal program. We will consider them as supportive 2 evidence, ancillary evidence," and so on. 3 Q. As an investigator and as an individual with Lilly 4 as one who is interested in the safety of fluoxetine, whether 5 or not the study is pivotal or nonpivotal doesn't really have 6 any relevance to the safety of the drug, does it, Doctor? 7 A. Not at all; not at all; not at all. 8 Q. And whether or not a drug will be safe is not 9 dependent upon whether or not the study is pivotal or 10 nonpivotal. 11 A. No; it's not even dependent upon its 12 efficaciousness. 13 You can have a compound that's efficacious and not 14 safe, and you can have a compound that is not efficacious 15 that's very safe, and those things are separated out. 16 If you'll notice, the efficacy and the safety are 17 two absolute separate entities that are analyzed as totally 18 separate things. 19 Q. All right. Did you use Dr. Howard Masco? Have we 20 discussed Dr. Masco? 21 A. Yeah, I believe. Yeah. He said yes. He's just 22 up north of Tampa; we didn't decide on the town. 23 Q. How about Dr. Karl Rickels, did you use Dr. Karl 24 Rickels? 25 A. Yeah; he's still at the University of 197 1 Pennsylvania. 2 Q. How about Dr. Ward Smith? 3 A. Oregon, yes. 4 Q. Forgive me if I repeat some of these names. I 5 believe they need repeated. 6 A. Sure. 7 Q. How about Dr. Rudolph Noble, did you use Dr. Noble 8 as an investigator? 9 A. San Francisco; obesity, though. Obesity, San 10 Francisco. 11 Q. You did use him? 12 A. For obesity studies. 13 Q. With respect to fluoxetine? 14 A. Yes. 15 Q. With respect to a protocol that you had designed? 16 A. Yes. 17 Q. Dr. Louis Lemberger? 18 A. Gave him lots of work. He worked for Lilly; he 19 headed up the Lilly Clinic. 20 Q. Did Dr. Lemberger do any studies? 21 A. He did all the phase one work for Lilly at the 22 Lilly Clinic. He was a Lilly employee. 23 Q. Did he do any studies for you -- 24 A. He couldn't. 25 Q. -- in response to a protocol that you prepared? 198 1 A. No, he couldn't. He was a Lilly employee, he 2 couldn't work for me. 3 Q. Well, is it your testimony that Dr. Lemberger only 4 participated in phase one studies as far as you know? 5 A. In conduction of studies, no. Lou Lemberger did 6 the 30/20 protocol with someone, whoever it was he worked 7 with. 8 Q. Was that a phase one study? 9 A. No; that was the very first phase. Remember the 10 one I told you, we tried giving thirty, dropping it down to 11 twenty, and it didn't work. Remember, we talked about that 12 earlier? 13 Q. Uh-huh. 14 A. That's the one that I think he played a part in. 15 He wouldn't have done anything for me, though, because he's a 16 Lilly employee. He was actually higher than me in the 17 hierarchy, except I never reported to him or through him. He 18 was a separate group. 19 Q. Let me ask you this way: Do you know of any 20 instances where he did any investigation as a clinical 21 investigator following a protocol that you had designed with 22 respect to fluoxetine? 23 A. He never did, no. 24 Q. The answer to that is absolutely not. 25 A. No. That's correct. 199 1 Q. How about Dr. Stanley Fahn, F-A-H-N? 2 A. Not triggering me this time. 3 Q. You don't know Dr. Fahn? 4 A. Doesn't ring a bell. That's all I can answer you. 5 Q. How about Dr. G.R. Aronolf? 6 A. I think I've finally failed the semester. 7 Q. How about Dr. J.J. Manigan? You don't know Dr. 8 Manigan? 9 A. I don't remember Dr. Manigan, he or she. 10 Q. How about Dr. Donald F. Klein? 11 A. Don Klein, yeah, I know him. 12 Q. Did he do any investigations on any of the 13 protocols that you designed? 14 A. Boy, I don't recall. 15 Don Klein, is this the one at Columbia, New York? 16 Q. I believe so. 17 A. Does lactic acid for panic is what he's known for. 18 I don't remember running those studies. I visited with him, 19 but I can't remember why. 20 Q. Would it have been with respect to fluoxetine? 21 A. This is what I don't know. I just don't know. 22 Q. How about Dr. Samuel Turner? 23 A. University of Pittsburgh. 24 Q. Did he do work as an investigator for you with 25 respect to fluoxetine? 200 1 A. He did work for me as an investigator; I don't 2 remember the drug. 3 Q. How about Dr. David L. Dunner, D-U-N-N-E-R? 4 A. Yep. 5 Q. Where is Dr. Dunner located? 6 A. Seattle, Washington. 7 Q. And what did he do for you? 8 A. I don't recall. 9 Q. Did he do work for you in connection with 10 fluoxetine? 11 A. I don't recall, but he's done several studies with 12 me; I just don't recall the drugs I've done with him, though. 13 Q. Have we mentioned Dr. Fabre, F-A-B-R-E? 14 A. Lou Fabre, no. 15 Q. Yeah. 16 A. You didn't mention him, but you did now. 17 Q. Has Dr. Fabre -- where is Dr. Fabre located? 18 A. Houston. 19 I feel like I'm on a challenge now, can I remember 20 where they are from. 21 Lou Fabre has done lots of studies, but, once 22 again, I can't tell you that he did fluoxetine. The 23 probabilities are very high on a statistical basis, but I 24 don't know if I can answer you. 25 Q. Is Dr. Fabre in your opinion a competent, thorough 201 1 investigator? 2 A. Yeah. 3 You know, like everyone else, he has his 4 weaknesses and his strengths, but when I heard you ask the 5 question, I evaluated him. I said, "Is he competent?" and 6 is -- he's got an outstanding reputation. He's one of those 7 people that the entire pharmaceutical industry will rely on 8 very extensively to very quickly be able to determine if a 9 drug is acting or not acting in a positive way. 10 He has a propensity to drop patients after two 11 weeks if they haven't responded and move them on to existing, 12 available medication. His feeling is that if it hasn't 13 worked in two weeks, he doesn't care if it's going to come on 14 in three weeks, he's going to go back to what is stable, but 15 he's very good. 16 You can meet with him and he will explain to you 17 the details and the theoretical mechanisms of action of any 18 drug on the market today. He's one of those good 19 practitioners who doesn't just give a drug just because it's 20 there; he gives it for a very good reason to his patients 21 because he knows pharmacologically how it works, and so 22 that's why I think so very highly of him. 23 If I had to be treated, that's the type of person 24 I'd want treating me, and if you keep on like this, I'm going 25 to need it. 202 1 Q. What? 2 A. If you keep on like this, I'm going to need it. 3 Q. Is he a neuropsychologist? 4 A. No; he's a psychiatrist. 5 Q. Neuropsychiatrist, or just a straight 6 psychiatrist? 7 A. He's a board registered psychiatrist -- board 8 certified, I guess; excuse me. 9 Q. How about Dr. Roland J. Branconnier? 10 A. Branconnier, yes. 11 Q. Branconnier? 12 A. Ronald Branconnier. 13 Q. Where is he located? 14 A. Outside of Boston. 15 Q. Has he done work as an investigator for you 16 concerning protocols you've drawn up with respect to 17 fluoxetine? 18 A. I don't know if it's fluoxetine, I can't recall, 19 but he has done protocols that I have written. 20 Q. How about Dr. Allan Childs? 21 A. Who? 22 Q. Allan Childs, C-H-I-L-D-S? 23 A. You got me again. 24 Q. You don't -- name doesn't ring a bell, you don't 25 know Dr. Childs? 203 1 A. No, I can't recall. 2 Q. How about Dr. Crismon, do you know Dr. Crismon? 3 A. I wonder if some of these guys work for someone 4 else. I really -- they don't ring a bell. If they are not 5 the principle investigator, I can't bring them back up. I'm 6 sorry. 7 Q. Roland R. Fieve, F-I-E --. 8 A. Fieve? 9 Q. Fieve? 10 A. Yeah, Roland Fieve, New York. 11 Q. Has he done work as an investigator with respect 12 to fluoxetine on the protocols that you've drawn up? 13 A. He's done studies with regard to protocols that 14 I've drawn up, and I can't recall whether he specifically did 15 fluox or not. 16 Q. How about Eric Dessain, D-E-S-S-A-I-N? 17 A. You see, you're getting -- now, Eric Dessain, if 18 that's who I think it is, he worked with Roland Branconnier, 19 and so these other names you may have been pulling may have 20 been working with these people. 21 It so happened the name Eric rang a bell with me, 22 but, you see, my focus was on the PI, the principle 23 investigator, all the time. So, you see, now whether Childs, 24 Crismon, and I forget what other names you asked me about, 25 worked with some of the other people, that's possible, but I 204 1 can't conjure up their names. 2 I thought I did relatively well telling you where 3 all these people were from. 4 Q. Where is Dessain from? 5 A. He should be in the Boston area, too, then with 6 Roland Branconnier. 7 Q. How about Dr. Ram K. Shrivastava, 8 S-H-R-I-V-A-S-T-A-V-A? 9 A. Don't even spell it. I don't know. 10 MR. MURGATRAOYD: Shrivastava. 11 A. Oh, Shrivastava. Oh, sure, Ron Shrivastava. Oh, 12 yes, I know him. He's in the New York area, too. 13 Q. Has he done work with fluoxetine with respect to a 14 protocol that you prepared? 15 A. I have to give you the same answer: I can't 16 answer for sure. 17 On a statistical basis, the probabilities are in 18 your favor. 19 Q. Joseph Mendels? 20 A. Joe Mendels, yes. 21 Q. Where is he located? 22 A. Philadelphia. 23 You got to give me a few points. You haven't 24 smiled in about three or four minutes now. 25 MR. FREEMAN: He's getting tired, too. 205 1 BY MR. PAUL SMITH: 2 Q. Where is Dr. Mendels? 3 A. Philadelphia. 4 Q. And has he done work for you as an investigator of 5 the fluoxetine clinical trials? 6 A. He has done studies for me on protocols that I've 7 drawn up; I cannot specify fluoxetine. 8 Q. Now, each of these investigators that you 9 contacted or that you used with respect to fluoxetine who did 10 clinical trials according to protocols drawn up by you, is it 11 your testimony that you personally met with each one of those 12 individuals? 13 A. Yes, it is. 14 Q. And would you usually go to their location, 15 wherever they were? 16 A. Yes. 17 Q. And the purpose of that meeting would be to 18 interview --? 19 A. Oh, I'm sorry, I thought you stopped in the middle 20 of a sentence. 21 The purpose of the meeting would be to --? 22 Q. To interview that person. 23 A. That is correct. 24 Q. To determine what? 25 A. How I felt about them with regards to their 206 1 competency, their staff, their facilities, the ease with 2 which I could stay closely working with them for a year to 3 two years; all the things that would make for a smooth study, 4 those things which are obvious scientifically, but both 5 personality-wise is important as well. 6 Q. Would you make notes of those interviews? 7 A. Not that I recall. You asked me that this 8 morning, too. 9 Q. That's what I thought I did -- 10 A. Yeah. 11 Q. -- is I asked you. 12 Would you take these investigator packages or 13 package with you when you visited with them? 14 A. What's an investigator package? 15 Q. A package that, as I understand it, was used that 16 reflected the past trials and data concerning fluoxetine, for 17 instance, phase one data potentially. 18 A. Would I take them with me? 19 Q. Yes. 20 A. No. 21 Q. How would they be transmitted to the investigator? 22 A. Well, it would depend, first of all, whether the 23 people that I visited ever became involved with us in doing 24 studies. 25 Q. So they wouldn't get the package unless they were 207 1 hired. 2 A. Yeah, then they'd get an investigator's brochure 3 which has to be put together and has to be updated regularly. 4 That's another regulatory requirement, as you know. 5 Q. Investigator's -- 6 A. -- brochure. 7 Q. And you say there's -- I really didn't know this. 8 Are there FDA regulations? 9 A. Yeah. You have to update them on a fairly regular 10 basis. As you get more and more information, that's all to 11 be added into the brochure at all times, so that when an 12 investigator gets a brochure, he has a current picture of 13 what's been happening, what's been done, what types of 14 studies have been done, the incidences of side effects as 15 compared to huh, huh, huh, and so on. This is standard; 16 every drug firm does it. 17 Q. What's it look like? 18 A. A loose-leaf binder. That (indicating) would be 19 too big. You can't -- none of the investigators can read 20 that long, that I know. Maybe, yea (indicating) thick. 21 Q. Inch and a half thick? 22 A. Yeah; and you have various sections. You usually 23 have a very small chemistry section, but the main thing they 24 are interested in, of course, is the clinical section, and so 25 you keep updating. That's why it has to be updated as more 208 1 and more studies are done, yearly, biyearly. Depending on 2 the extent of your clinical activity, you update it. 3 Q. Do those investigator brochures have to be 4 submitted as part of the I&D or NDA? 5 A. I don't know. I know the IRB's all get copies of 6 them, as well as the investigator. Whatever IR -- 7 Institutional Review Board that they are using, an 8 investigator's brochure gets sent to the IRB's as well. 9 Q. Wait a minute. Institutional Review Board? 10 A. God, have I opened another can of worms? 11 MR. MURGATROYD: You sure did. 12 THE WITNESS: Can I go home now? 13 MR. MURGATROYD: Twenty more minutes. 14 MR. FREEMAN: No, five more minutes. 15 MR. MURGATROYD: Five more minutes? 16 MR. FREEMAN: Yes. It's 4:20, I can't stand any 17 more of the doctor's time. We're exhausted and we're 18 worn to a frazzle. 19 MR. MURGATROYD: We're just warming up. 20 BY MR. PAUL SMITH: 21 Q. What's the Institutional Review Board, Dr. Stark? 22 A. A federal regulatory requirement is that a 23 protocol must be approved by an Institutional Review Board, 24 and they spell out in the ranks what it must be comprised of. 25 I don't know the whole thing, but there has to be 209 1 like a minister, a lawyer, like the patient's advocate type 2 of thing, physician, social worker, and has to be like five, 3 six, seven, eight, nine people. It can vary in size, but it 4 has to have basic requirements, and they then will review the 5 protocol and see to it that in each of their respective 6 interest areas it meets their criteria of being appropriate 7 to give to a patient, the physician with regards to safety or 8 the appropriate patient population, and the consumer 9 advocate, that the patient is getting something in return for 10 his volunteering. It goes on and on. 11 There's even -- oftentimes some will have a 12 religious person in there, I haven't figured that out yet; 13 but, nonetheless, that's all part of the thing. And they 14 review the protocol and they review even the informed consent 15 that a patient doesn't agree to do something that's not 16 really in their appropriate interest, and there are basic 17 requirements by federal statute what must be at least 18 included in an informed consent. Those are all very clearly 19 defined in the lit -- I'm telling you stuff you know, I can 20 tell; you're falling asleep. 21 That all gets reviewed, then they give you back if 22 they want to sit and change, if they think something is 23 unfair, this and that, and then they approve it; and then 24 every year they have to be undated as to whether the study is 25 still ongoing or not, and any serious adverse events have to 210 1 be reported to them so they have an opportunity, if they 2 chose to, to say, "This study is going to stop at this site. 3 I think it's inappropriate." 4 So the IRB always gets not only the protocol, but 5 the investigator's brochure, as well as the investigator. 6 That's how we ended up telling you about that. 7 Q. The Institutional Review Board, is that -- are the 8 members selected by someone? 9 A. You know, they vary considerably, but most people 10 use an IRB at a hospital, and the reason for that is if they 11 don't use a hospital one where they practice, if ever an 12 emergency comes up, they get static that the IRB there says, 13 "Why should I let this patient in? I never approved that 14 protocol to begin with." 15 So it's much easier to upgrade, and they are 16 usually in existence at every hospital. So wherever that 17 physician does have hospital practicing privileges, he 18 usually uses the IRB that's there and is in existence; and 19 you have to submit to the FDA the names, addresses and 20 occupations of every member of an IRB. This is all spelled 21 out in the statute. 22 Q. Okay. So is what you're saying that if we had an 23 investigator in Boston -- 24 A. Yes, sir. 25 Q. -- that there would have to be an Institutional 211 1 Review Board in whatever hospital that physician --? 2 A. It wouldn't have to be at the hospital. It 3 oftentimes is, but there are IRB's that are available that 4 are set up to take care of this that are meeting all the 5 criteria of the FDA. 6 Now, there are such things called Central IRB's. 7 Q. All right. What is a Central IRB? 8 A. And the Central IRB -- well, the one that comes to 9 my mind is the Western IRB, which is somewhere in Seattle, or 10 something like that, and they are in business. They are 11 probably one of the best, but not all investigators can use 12 them, because while by law they can do a study, the fact of 13 the matter is, at their local area they couldn't. And the 14 law really says that, where possible, the local IRB should be 15 used as it pertains to that particular and local community 16 So if you really want to do it right to the extent 17 that's possible, you should always use the local IRB. If 18 you're doing a very large surveillance study at two hundred, 19 three hundred, a thousand sites across the country with just 20 a few patients, with people who are merely practicing 21 psychiatrists and strictly a safety study, and they are 22 people who indeed can practice good medicine, but don't know 23 rating scales, where rating scales are impertinent anyway, a 24 Central IRB becomes indeed a very, very useful type of thing. 25 So the ethics are maintained and yet the 212 1 practicing physician can practice his skills. 2 Can I go home now? 3 (Discussion off the record.) 4 THE WITNESS: I'm really, gone, guys. 5 BY MR. PAUL SMITH: 6 Q. Just a couple of follow-up questions. 7 The parts of the -- are there parts of the 8 investigator's brochure that are deleted as the updates come 9 out? 10 A. No. Everything should be there, and it should be 11 expanded. At a point in time if it ever gets too big, you 12 can do more of a summary, but everything should be in there; 13 the whole picture should always be there. 14 MR. PAUL SMITH: All right. 15 MR. FREEMAN: Thank you, guys. 16 MR. MURGATROYD: Thank you, all. 17 (Deposition recessed for the day at 4:20 p.m.) 18 19 20 21 22 __________________________ _______________________________ Date PAUL STARK, Ph.D. 23 24 25 213 1 STATE OF_____________) 2 COUNTY OF____________) 3 4 I, ______________________________, a Notary Public in 5 and for the State of______________at Large, do hereby certify 6 that the foregoing deposition of PAUL STARK, Ph.D. was 7 subscribed in my presence on the ______ day of ______________ 8 1993. 9 10 IN WITNESS WHEREOF, I have hereunto subscribed my name 11 and affixed my seal, the date hereinabove mentioned. 12 13 14 15 _______________________________ Notary Public 16 State of_______________at Large 17 My Commission Expires: ________ 18 19 20 21 22 23 24 25 214 1 STATE OF FLORIDA ) 2 COUNTY OF LEE ) 3 I, Debra L. Gunn, CP-RPR, Notary Public, in and for the 4 State of Florida at Large, do hereby certify that the 5 foregoing videotaped deposition of PAUL STARK, Ph.D. Was 6 taken before me, in the cause, at the time and place, and in 7 the presence of counsel, as stated in the caption hereto, at 8 Page 1 hereof; that before giving his deposition said witness 9 was duly sworn by me to testify the truth, the whole truth, 10 and nothing but the truth; that the foregoing typewritten 11 transcription, consisting of pages number 1 to 213, 12 inclusive, is a true record of my stenographic notes of the 13 testimony of said witness and of all proceedings had at the 14 session at which said deposition was taken. 15 IN WITNESS WHEREOF, I have hereunto subscribed my name 16 and affixed my seal, this the 12th day of March, 1993. 17 18 19 _______________________________ Debra L. Gunn, CP-RPR 20 21 22 23 24 25