1 1 NO. 90-CI-06033 JEFFERSON CIRCUIT COURT DIVISION ONE 2 3 4 JOYCE FENTRESS, et al PLAINTIFFS 5 6 VS TRANSCRIPT_OF_THE_PROCEEDINGS __________ __ ___ ___________ 7 8 9 SHEA COMMUNICATIONS, et al DEFENDANTS 10 11 * * * 12 13 14 FRIDAY, OCTOBER 21, 1994 15 VOLUME XX 16 17 * * * 18 19 20 21 _____________________________________________________________ REPORTER: JULIA K. McBRIDE 22 Coulter, Shay, McBride & Rice 1221 Starks Building 23 455 South Fourth Avenue Louisville, Kentucky 40202 24 (502) 582-1627 FAX: (502) 587-6299 25 2 1 2 I_N_D_E_X _ _ _ _ _ 3 4 Hearing in Chambers...................................... 4 5 * * * 6 WITNESS: DOCTOR_ROBERT_ZERBE - By Written Deposition _______ ______ ______ _____ 7 Examination by Ms. Zettler (As read by Mr. Smith)........ 17 8 * * * 9 Reporter's Certificate................................... 91 10 * * * 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 3 1 2 A_P_P_E_A_R_A_N_C_E_S _ _ _ _ _ _ _ _ _ _ _ 3 4 FOR THE PLAINTIFFS: 5 PAUL L. SMITH Suite 745 6 Campbell Center II 8150 North Central Expressway 7 Dallas, Texas 75206 8 NANCY ZETTLER 1405 West Norwell Lane 9 Schaumburg, Illinois 60193 10 FOR THE DEFENDANT: 11 EDWARD H. STOPHER 12 Boehl, Stopher & Graves 2300 Providian Center 13 Louisville, Kentucky 40202 14 JOE C. FREEMAN, JR. LAWRENCE J. MYERS 15 Freeman & Hawkins 4000 One Peachtree Center 16 303 Peachtree Street, N.E. Atlanta, Georgia 30308 17 18 * * * 19 20 21 22 23 24 25 4 1 The Transcript of the Proceedings, taken before 2 The Honorable John W. Potter in the Multipurpose Courtroom, 3 Old Jail Office Building, Louisville, Kentucky, commencing on 4 Friday, October 21, 1994, at approximately 7:55 A.M., said 5 proceedings occurred as follows: 6 7 * * * 8 9 (THE FOLLOWING HEARING ON OBJECTIONS WAS 10 HEARD IN DIVISION ONE OF THE JEFFERSON 11 CIRCUIT COURT, HALL OF JUSTICE) 12 13 JUDGE POTTER: If my memory is correct, Doctor 14 Zerbe is a former Lilly employee; is that where he is? 15 MS. ZETTLER: Yes, sir. 16 JUDGE POTTER: And who was he? 17 MR. MYERS: He worked for Doctor Leigh Thompson. 18 He was in charge of, at various times, clinical trials and 19 regulatory affairs. 20 MS. ZETTLER: And worldwide regulatory affairs 21 at one point outside the United States, or foreign. He was at 22 a higher-level or middle-level management in foreign, 23 generally. 24 MR. MYERS: He worked overseas. 25 JUDGE POTTER: Page 51, they get to cheerlead. 5 1 MS. ZETTLER: Do we have to read that or do they 2 read that in? 3 JUDGE POTTER: No. If it's just a few, read all 4 through them. 5 MR. MYERS: What's the next one, Nancy, 142? 6 MS. ZETTLER: Yeah. 7 It's completely gratuitous, Judge. 8 JUDGE POTTER: Well, let me give you-all a CLE 9 credit. There's no objection called self-serving; there's no 10 objection called gratuitous. 11 MS. ZETTLER: But we're going to bring these 12 people in, and then you force us to read things that they 13 would have to get out on their cross, or their direct. 14 JUDGE POTTER: But the point is, they could have 15 gotten it out on examination of this fellow on 16 cross-examination and they didn't because it was in there. 17 MS. ZETTLER: They didn't ask anybody any 18 questions, Judge. 19 JUDGE POTTER: That's right. And I'm sure we'll 20 hear about it on closing argument, that none of these people 21 were cross-examined. They didn't -- they have a decision 22 shall I cross-examine this witness. Shall we? No. 23 Everything we want in, he's already said. If it was something 24 major, I might make them read it like it was on 25 cross-examination, but this is just a... 6 1 MS. ZETTLER: Just for the record, it's 2 prejudicial to make us read those portions. It goes beyond 3 reading for completeness, and I think the rule says that it's 4 discretionary that they can make us read it for something that 5 completes a thought, but these things are taken out of 6 context. 7 JUDGE POTTER: Well, it's short, and for them to 8 go back and read it as part of their deposition, it's -- it 9 wouldn't really be -- it would be confusing, so let me see one 10 other thing. Okay. 146 and 147. 11 MR. MYERS: I got behind. 12 JUDGE POTTER: You won 142 and 143. 13 MR. MYERS: What about 144 and 145? Is that 14 what you're looking at now? 15 MS. ZETTLER: I thought you said you took that 16 out. 17 MR. MYERS: No. 12 through 24 on 144 and 18 1 through 6 on 145. It's in between a designation. 19 JUDGE POTTER: Okay. I see. 20 MS. ZETTLER: Larry, I already said I'd put that 21 in. I'm sorry, Judge. 22 MR. MYERS: I'm sorry, too. I apologize. 23 JUDGE POTTER: Okay. 146 and 147. 24 MR. MYERS: I'll withdraw the objection on 146 25 if you take out Lines 3 and 4, where he says that it was 7 1 speculation; if not -- 2 MS. ZETTLER: Will you withdraw the page 3 designations, too? 4 MR. MYERS: No. 5 MS. ZETTLER: Forget it, then. 6 MR. MYERS: Lines 3 and 4 are the ones I really 7 have a problem with. 8 JUDGE POTTER: This is where he gets to -- 9 MS. ZETTLER: Can I see it again, Judge? This 10 whole answer, if I'm not mistaken, is completely 11 nonresponsive. If you want to cut it off here, that's fine, 12 but he just goes on and on and on and on and on. 13 JUDGE POTTER: We're going to hear it a thousand 14 times and that's why they didn't give it to you. 15 Mr. Myers, you get 146 through 148, Line 2. 16 MR. MYERS: My objection then is overruled? 17 JUDGE POTTER: Your objection is sustained. 18 MS. ZETTLER: He's talking about the other one, 19 Judge. 20 JUDGE POTTER: Yeah, that's overruled. 146, his 21 objection is overruled. 146 through 148, the objection is 22 sustained. 23 MR. MYERS: I took all of 154 out, or one line 24 on 154. 25 JUDGE POTTER: (Reviews document) Okay. 8 1 Mr. Myers, on 155 and 156, if you want to read that as part of 2 cross... You know what I mean? When they get through if you 3 want to say, "Doctor, I have one more question" and read that, 4 you can, because it's out of sync with all of what she's 5 doing. 6 MR. MYERS: All right, sir. 7 JUDGE POTTER: 228 is where we are? 8 MR. MYERS: Yes, sir. 9 MS. ZETTLER: Yes. 10 MR. MYERS: I believe we're entitled to prove 11 who he is. 12 MS. ZETTLER: You just want to get in that he's 13 board certified. I think that comes under if they want to 14 read it they can read it on their own part. 15 MR. MYERS: My concern is they're going to ask 16 him a lot of these medical questions, and I think he's 17 entitled to say, "I'm a doctor and I'm board certified." 18 MS. ZETTLER: He did, but there's a difference 19 between -- 20 JUDGE POTTER: Wait. Wait. (Reviews document) 21 I'm going to do something even worse to you, Ms. Zettler. I'm 22 going to do something even worse to you than allowing him to 23 get it in. I'm going to ask you when you Xerox it if you 24 would read it after Page 25, because that's when they're 25 talking about -- they want to get in that he's a doctor. "Why 9 1 don't you give us a little bit of background with regards to 2 your education after high school," and then move that 3 sentence, "As I understand it, you received your M.D. degree, 4 did you not? 5 "Yes. 6 "When and where?" 7 Do you understand what I did, Mr. Myers? 8 MR. MYERS: Yes, sir. It's going to be moved 9 up. 10 JUDGE POTTER: Yes. 11 MR. MYERS: This goes to the next volume. 12 MS. ZETTLER: It's like saying just because you 13 take the boards you're ethical. 14 JUDGE POTTER: My concern here is not so much 15 the gamesmanship of it as trying to get what I've got in a 16 thing that's the most easily simulated by the jury, and 17 putting all his education together... 18 All right. Deposition August 9th, 36 and 37. 19 MR. MYERS: Judge, Page 32 and 33 relate to our 20 OUS motion, and if that's already been overruled I'm not 21 withdrawing the motion but I'm not going to insist on it as I 22 sit here now, just as long as I don't waive anything. 23 JUDGE POTTER: Gosh, if I sustain this one we 24 have to go back and start the trial over. 25 MS. ZETTLER: Don't do that. I'll get divorced. 10 1 JUDGE POTTER: Okay. 36. What is Exhibit No. 2 11? Exhibit No. 11 is marked and identified, and then you 3 talked about it for three pages. 4 MS. ZETTLER: Only the things with the black 5 lines are in still. I'm not even using Exhibit 11 now. 6 JUDGE POTTER: 36, 27 and 38 are out? 7 MS. ZETTLER: Right. 8 JUDGE POTTER: All right. What about 40, 41? 9 MS. ZETTLER: That should be the same. 10 JUDGE POTTER: If it's just pink it's in? 11 MS. ZETTLER: So 40 and 41 goes out, too, then, 12 doesn't it, because you said read for completeness compared to 13 before and after? 14 MR. MYERS: I'm sorry. No. Because at the end 15 on Page 42 and 43, if you look at that whole string of 16 read-for-completeness objections through 43, you've designated 17 Lines 23 and 24 on 42, and 1 through 5 on 43, which go to this 18 activation/sedation question. That's why I want it in. 19 MS. ZETTLER: But this is all around that 38 20 percent and everything else. 21 MR. MYERS: But they're still reading the bottom 22 of 43, 23 through 24. 23 JUDGE POTTER: Is that what your 40, 41 through 24 43 is? 25 MR. MYERS: Right. Because that still has to do 11 1 with the same subject; that's what I meant. 2 So, Nancy, you're correct that the "before" part 3 no longer applies. 4 MS. ZETTLER: Right. But... 5 JUDGE POTTER: Mr. Myers, do you want to look at 6 42? 7 MS. ZETTLER: That's his objection. 8 JUDGE POTTER: That's his objection. All right. 9 Well, I'm looking at his 42, 17 through 22. That's just an 10 answer. 11 MS. ZETTLER: Yeah. 12 JUDGE POTTER: What did you mean when you wanted 13 to read 17 through 22? That's just an answer. 14 MR. MYERS: I think what I meant was that -- 15 well, they pick up on line -- we would start then on Line 3, 16 I guess, instead. It should go back, I think, to Line 3 17 because that's the last complete question. 18 MS. ZETTLER: But the reason I took that out is 19 because he's talking about a document there and that document 20 has not come in. And this guy's not going to say he knew it, 21 either, and I don't want to go through the whole diatribe 22 again. 23 MR. MYERS: I'm not going to insist on 43, 17 24 through 22, but I think that 40 and 41 should still be read. 25 JUDGE POTTER: I'm going to read 40 and let him 12 1 do 40 and 41. He's taking out the added 42, and I'm 2 overruling your objection to 42 and 43. 3 MR. MYERS: All right, sir. 4 I'll withdraw the objection to 48 through 52. I 5 just looked at that again. 6 MS. ZETTLER: 61 through 63. That's another one 7 that's taken completely out of context, Judge. 8 JUDGE POTTER: Wait. Wait. (Reviews document) 9 All right. 61 through 63, I'm going to allow you -- obviously 10 you-all can read it at the end as if on cross-examination if 11 you want to, because it's out of the flow of what's going on. 12 74 through 84. 13 MR. MYERS: Wait a minute. 65, I assume, is 14 overruled; that has to do with the OUS again, but 68 and 69. 15 If you're going to admit -- 16 JUDGE POTTER: I didn't pick up that was still 17 something I had to do with. 65 is overruled. 68 and 69. 18 MR. MYERS: I'll tell you what. I'll take those 19 out. I'll withdraw that. 20 JUDGE POTTER: 74 through -- 21 MS. ZETTLER: 84. 22 JUDGE POTTER: What is Erl Wood? 23 MS. ZETTLER: It's one of those affiliates in 24 England. 25 MR. MYERS: It's a research facility. They'd 13 1 say England, Scandanavia, Erl Wood. 2 MR. MYERS: The names of the places in England 3 are just by the city since they have three or four places over 4 there. 5 JUDGE POTTER: Another word came up yesterday, 6 when you get a live witness you have to define for the jury. 7 I doubt if half of them know what contraindicated means. 8 MS. ZETTLER: Okay. 9 JUDGE POTTER: All right. Save me reading all 10 this. What is phospholipidosis? 11 MS. ZETTLER: I have it now, Judge. It's an 12 accumulation of cells of sorts within the lungs. 13 JUDGE POTTER: Okay. 14 MR. MYERS: Of animals. It's never been seen in 15 humans. 16 MS. ZETTLER: The purpose of this is they gave 17 this to an expert in psychology to look at the 18 phospholipidosis; this guy on his own sees that he's got CNS 19 stimulation. That's the point of this. 20 JUDGE POTTER: Let me get to that part of it... 21 MR. MYERS: There's reference of 22 phospholipidosis in some of these German documents in passing, 23 but this is just an entire discussion of this subject which is 24 neither here nor there. 25 JUDGE POTTER: But she says this guy is going to 14 1 say, by the way, this is central nervous system stimulating? 2 MS. ZETTLER: Right. Which relates to the 3 pharmacology of the drug. 4 JUDGE POTTER: (Reviews document) I'm going to 5 do you a favor. I'm going to sustain his objection on that. 6 MS. ZETTLER: You don't want to hear about 7 phospholipidosis? 8 JUDGE POTTER: No. Not for one line that says 9 CNS, et cetera. 221. 10 MR. MYERS: Okay. Because then 84 wouldn't 11 apply. 12 MS. ZETTLER: This is another OUS objection, 13 isn't it? 14 MR. MYERS: Wait a second. Oh, I'm sorry. What 15 about 117 and 118 and 208? 16 MS. ZETTLER: I think I put those back in. 17 MR. MYERS: If you did, you didn't tell me. 18 MS. ZETTLER: Yes, I did. You've got to get 19 with it, Larry. 20 MR. MYERS: 117, 118 and 128. I assume 221 is 21 overruled? 22 MS. ZETTLER: That OUS stuff. 23 MR. MYERS: Then the next one would be 226. 24 What is CSM? 25 MS. ZETTLER: Committee on Safety in Medicine. 15 1 JUDGE POTTER: That's the British -- 2 MS. ZETTLER: BGA, FDA, yeah. 3 JUDGE POTTER: Ms. Zettler, what is 27? I mean, 4 his objection is that this guy hasn't seen it. What is it? 5 MS. ZETTLER: I believe it's a memo regarding -- 6 I guess it's a draft of a letter by CSM talking about their -- 7 JUDGE POTTER: How do we know that's what it is? 8 MR. MYERS: I don't know what it is. We 9 produced it, obviously, but there's no identifier to speak of 10 on it. 11 JUDGE POTTER: I'm going to sustain the 12 objection. You may be able to get it in some day some way 13 later, but... 14 MR. MYERS: 229 through 239. That's more 15 outside the U. S. I assume that's overruled. I won't even 16 make the Court -- 17 JUDGE POTTER: Okay. Thank you-all. 18 MS. ZETTLER: Okay. Thank you, Judge. 19 MR. MYERS: Thank you, sir. Thanks for your 20 time. 21 (HEARING ON OBJECTIONS ENDS AT 8:28 A.M.; 22 THE FOLLOWING BENCH DISCUSSION OCCURRED 23 AT ABOUT THE HOUR OF 10:10 A.M.) 24 MS. ZETTLER: He wants to designate just this 25 part here and not this now. 16 1 MR. MYERS: My problem, Judge, is that that in 2 closer examination, understanding it was 7:30 this morning, 3 the reference part Line 10 through 24 on Page 40 and 1 through 4 4 on Page 41 deal with the document that they're not going to 5 offer and, on closer examination I recognized it, and for that 6 reason I want it out. I just did not examine it closely 7 enough. 8 JUDGE POTTER: Let me take a quick look at it. 9 Is this the second day or the first day? 10 MS. ZETTLER: He's looking at this. 11 MR. MYERS: I want to stop on Line 9 on Page 40. 12 JUDGE POTTER: It's truly six of one and a half 13 dozen of another. 14 MS. ZETTLER: We think it should be all in 15 there, Judge. 16 MR. MYERS: My point is it refers to a document 17 they're not going to offer. 18 JUDGE POTTER: I'll sustain it. 19 (BENCH DISCUSSION CONCLUDED) 20 SHERIFF CECIL: Jurors are entering. All jurors 21 are present. Court is now in session. 22 JUDGE POTTER: Good morning. Seems like people 23 are a little more dressed up today than usual. So you've got 24 plans for this afternoon, huh? 25 Okay. I'm sorry. Mr. Smith, do you want to 17 1 call your next witness? 2 MR. SMITH: Yes, Your Honor. At this time, Your 3 Honor, we would offer the deposition or portions of the 4 deposition of Doctor Robert Zerbe. 5 JUDGE POTTER: Okay. Ladies and gentlemen, this 6 was a deposition that was taken and there was a transcript 7 made of it. In this particular case, the transcript or 8 portions of the transcript is going to be read to you. It may 9 be difficult for you because there's a natural tendency when 10 you see a live, real person to give it more effect than if 11 you're just hearing what somebody said, but you're going to 12 need to do the best you can to give this testimony the same 13 weight you would as if the person were here testifying live. 14 And basically what that means is when you're in the jury room 15 or when you're thinking about this information you somehow in 16 your own mind don't say, well, that doesn't count or it's not 17 as important because it was just given to us by deposition 18 than by the witness being here live. 19 Mr. Smith. 20 (THE FOLLOWING DEPOSITION WAS READ 21 BY MR. SMITH AS THE QUESTIONER AND 22 MR. WILLIAM NOLD AS DOCTOR ROBERT ZERBE) 23 MR. SMITH: This is the deposition of Doctor 24 Robert Zerbe, taken at the University Hotel, Ann Arbor, 25 Michigan, on May 13th, 1994, pursuant to the applicable rules 18 1 of civil procedure. This is direct examination beginning -- 2 by Ms. Zettler beginning on Page 12, Line 16. 3 Could you state your full name for the record, 4 Doctor. 5 A. Robert Lowell Zerbe. 6 Q. When did you leave Eli Lilly? 7 A. July of 1993. 8 Q. Was that to come to your present position? 9 A. Yes. 10 Q. And what is your present position? 11 A. I am senior vice-president for clinical research 12 at Parke-Davis. 13 Q. Have you been with Parke-Davis continually since 14 July of 1993? 15 A. Yes. 16 Q. In the same position? 17 A. Yes. 18 Q. Why did you leave Eli Lilly? 19 A. I just had a better opportunity. 20 Q. What was your position with Lilly when you left? 21 A. I was vice-president in charge of worldwide 22 regulatory affairs. 23 Q. How long had you been with Lilly at the time you 24 left? 25 A. Eleven years. 19 1 Q. When did you first start at Lilly? 2 A. In June of 1982. 3 Q. Did you work continuously for Lilly from June 4 1982 until July 1993? 5 A. Yes. 6 Q. Why don't you give us a little bit of background 7 with regards to your education after high school. 8 JUDGE POTTER: (To Mr. Nold) Doctor, that's your 9 microphone there, and if you put your paper over it, we get 10 feedback. 11 Why don't you back up a question, Mr. Smith. 12 MR. SMITH: Let's, Bill, start on Page 24, 13 Line 23. Got it? 14 MR. NOLD: Yes. 15 Q. When did you first start at Lilly? 16 A. June 1982. 17 Q. Did you work continuously for Lilly from June 18 1982 until July of 1993? 19 A. Yes. 20 Q. Why don't you give us a little bit of background 21 with regards to your education after high school. 22 A. I attended undergraduate school at Indiana 23 University, medical school at Indiana University, did 24 internship, residency and fellowship at Indiana, and then 25 spent two years at the National Institutes of Health prior to 20 1 joining Lilly. 2 Q. As I understand it, you received your M.D. 3 degree, did you not? 4 A. Yes. 5 Q. When and where? 6 A. 1975 at Indiana University. 7 Q. Then after you received your postgraduate 8 training or did postgraduate work, you did work in internal 9 medicine and endocrinology? 10 A. Yes. 11 Q. And thereafter became board certified in 12 internal medicine? 13 A. Yes. 14 Q. Are you board certified in any specialty of 15 medicine? 16 A. Internal medicine. 17 Q. And are you now or have you been a psychiatrist? 18 A. No. 19 Q. Have you ever had an interest in psychiatry 20 other than your work on Prozac? 21 A. Other than the usual interest in all aspects of 22 medicine, no. 23 Q. Have you -- did you do a residency in psychiatry 24 or internship in psychiatry during your medical school years? 25 A. No. 21 1 Q. Have you ever practiced psychiatry? 2 A. No. 3 Q. When did you become board certified in internal 4 medicine? 5 A. Let's see. It would have been approximately 6 1979, approximately. 7 Q. Have you ever prescribed Prozac? 8 A. No. 9 Q. How did you come to work at Lilly? 10 A. I was asked by a former associate to come and 11 consider a job. 12 Q. Okay. What was your first position with Lilly? 13 A. I was -- I'm not sure. I don't remember the 14 exact title, but I was an associate clinical pharmacologist or 15 something like that. 16 Q. How long were you an associate clinical 17 pharmacologist? 18 A. From June of 1982, until approximately October 19 of 1983. 20 Q. Okay. And what was your next position with 21 Lilly? 22 A. I was the director of the neuroendocrine 23 division. 24 Q. How long were you the director of the 25 neuroendocrine division? 22 1 A. From October of '83, until approximately June of 2 '85. 3 Q. What was your next position? 4 A. I was the director for clinical investigation in 5 Europe. 6 Q. How long were you the director for clinical 7 investigation in Europe? 8 A. From approximately July of 1985, until 9 approximately May of '87. 10 Q. Did you live over in Europe during that period 11 of time? 12 A. Yes. 13 Q. Where did you live? 14 A. I lived in Camberly, in Surrey, in England. 15 Q. Which affiliate did you work out of? 16 A. It wasn't really an affiliate; it was the Lilly 17 Research Center. 18 Q. Where is that? 19 A. It's in Wendelsham. 20 Q. I've seen some documents where it indicates that 21 you were working out of Erl Wood. Did you ever work out of 22 Erl Wood? 23 A. Yes. That's the Lilly Research Center. 24 Q. So the Wendelsham Research Center is known 25 commonly at Lilly as Erl Wood? 23 1 A. Yes. 2 Q. Were you at Erl Wood from approximately July of 3 '85 to approximately May of '87? 4 A. I was at Erl Wood beyond that time, as well. 5 Q. How long were you at Erl Wood? 6 A. Until approximately March of '89. 7 Q. Did you come back to The States at all for any 8 extended period of time during that period that you worked out 9 of Erl Wood, other than vacations and holidays and things like 10 that? 11 A. I'm not sure what you mean by an extended period 12 of time. 13 Q. Would you come back for, like, a month or so to 14 work out of the Indy office? 15 A. No. 16 Q. After your position as director for clinical 17 investigations in Europe, what was your next position at 18 Lilly? 19 A. I was the managing director at Erl Wood. 20 Q. How long were you the managing director at 21 Erl Wood? 22 A. From -- again, I don't want to confuse you on 23 the dates. From the time I left the job as director of 24 clinical investigation until I returned to the U. S. in March 25 of '89. 24 1 Q. Okay. So approximately May of '87 to March of 2 '89? 3 A. That's approximately right. 4 Q. Okay. What was your next position? 5 A. I was executive director for clinical 6 investigation and regulatory affairs. 7 Q. Executive director for clinical investigation 8 and regulatory affairs? 9 A. Something like that. 10 Q. How long were you in that position? 11 A. Well, I guess that title -- until I was promoted 12 to vice-president, which was I guess something like July of 13 1991, I think. 14 Q. When you say that title, did your 15 responsibilities change during that period of time in that 16 position? 17 A. There were various changes in responsibilities, 18 but my title never changed. 19 Q. Okay. Then you became vice-president of what? 20 A. It's Lilly Research Laboratories. 21 Q. And that was in July of 1991? 22 A. Yes. 23 Q. How long were you in that position? 24 A. Until I left. 25 Q. For two years, until July of '93? 25 1 A. That's right. 2 Q. When did you first start working with 3 fluoxetine? 4 A. In approximately November of 1983. 5 Q. After you had been sent over to Europe? 6 A. No. 7 Q. Oh, I'm sorry. What were your first 8 responsibilities with regards to Prozac or fluoxetine 9 hydrochloride? 10 A. I was responsible for the division, the 11 neuroendocrine division, and that division was responsible for 12 Prozac. 13 Q. Is the neuroendocrine division different than 14 the medical division? 15 A. Yes. 16 Q. Okay. What are the differences between the 17 responsibilities for the neuroendocrine division and the 18 medical division? 19 A. Well, the formal title "medical division," I'm 20 not sure that there's actually a formal organizational 21 structure called the medical division, but the neuroendocrine 22 division is one of the specialty areas within the larger 23 medical group. 24 Q. Was there a CNS division? 25 A. The central nervous system products were within 26 1 the neuroendocrine division. 2 Q. So you were in charge of the division that at 3 that time was responsible for developing and testing Prozac? 4 A. We had -- 5 Q. Clinical trials, animal studies, things of that 6 nature? 7 A. No animal studies, only the clinical trials done 8 by investigators outside of the company. 9 Q. Okay. How about healthy volunteer studies done 10 at the clinics? 11 A. No. I was not responsible for that at that 12 time. 13 Q. When you became responsible for the 14 neuroendocrine division, how much of your responsibility as 15 director of that division entailed Prozac as opposed to other 16 compounds? 17 A. I'm sorry. Could you repeat the question? 18 Q. Sure. I'm trying to get an idea of how much of 19 your time was spent working on Prozac as of November of '83. 20 A. I don't know. It would be an approximation. 21 Maybe 25 percent. 22 Q. Did there ever come a time when all of your 23 responsibilities were directly related to Prozac and you 24 weren't working on any other compounds? 25 A. No. 27 1 Q. I want to know if there was ever a time when the 2 majority of your time was spent working on Prozac as opposed 3 to other compounds. 4 A. Yes. There was a time that the majority of my 5 time was spent working on Prozac. 6 Q. When was that period of time? 7 A. I would say 1990, '91. 8 Q. Okay. So approximately a year within '90 and 9 '91? 10 A. Something like that. 11 Q. And that was when you were executive director of 12 clinical investigations? 13 A. Right. 14 Q. Was that the period of time between when Doctor 15 Teicher's article came out and the 1991 drug advisory 16 committee meeting? 17 A. Yes. 18 Q. How much of your time did you spend on Prozac 19 during that period of time? 20 A. Again, purely speculation, probably somewhat 21 over 50 percent of my time. 22 Q. Do you know if the final report of that study 23 was submitted to the FDA? 24 A. I can't personally verify it, but that would be 25 our standard procedure to submit it to the FDA, so I assume 28 1 that it was submitted. 2 Q. Any other questions raised by the German 3 government with regards to Prozac? 4 A. Specifically at the time of the inpatient study? 5 Q. No. Anytime that you're aware of. 6 A. Well, the Germans early on had questions about 7 suicidality. 8 Q. When you say "early on," what time frame are we 9 talking about? 10 A. Approximately 1986. 11 Q. Was it before or after you became director for 12 clinical investigations in Europe? 13 A. It was around the same time; I don't know 14 whether it was before or after, but it was around the same 15 time. 16 Q. What questions about suicidality did they raise? 17 A. They were concerned about the possibility of 18 activation with Prozac. 19 Q. When you say activation, what do you mean? 20 A. Well, I mean, I think they're probably better 21 able to describe what they meant exactly, but the concern was 22 that Prozac was a nonsedating antidepressant and that in their 23 minds, therefore, it was activating. 24 Q. Did they ask you to do any studies with regards 25 to the question of suicidality and the use of Prozac? 29 1 A. I can't recall exactly what they asked for, but 2 we did go back and look very carefully at the data base in 3 response to those questions and, well... 4 Q. What data base? 5 A. The data base that existed at that time, you 6 know, that Lilly had from clinical trials. 7 Q. Clinical trial data base? In other words, the 8 results of the various clinical trials that had been conducted 9 up until that period of time? 10 A. That's correct. 11 Q. Did that data base, to your knowledge, include 12 clinical trials that were conducted in the United States as 13 well as outside the United States? 14 A. I don't recall exactly which studies. I think 15 most of the studies were studies done in the U. S. 16 Q. Do you know how many studies have to date, or at 17 least until the time you left Lilly, had been conducted on 18 Prozac worldwide on depression? 19 A. A lot. I really don't know the number. 20 Q. Hundreds? 21 A. I would say hundreds. 22 Q. Okay. Now, do you define activation with 23 regards to -- okay. How do you define activation with regards 24 to fluoxetine, regardless of whether or not you feel it's 25 activating? 30 1 A. Well, activation, I think the perception with 2 regard to Prozac is that activation is the fact that it's 3 nonsedating specifically, you know, in regards to Prozac, and 4 that's the way I would look at it. 5 Q. Is it your understanding that many other 6 antidepressants that are currently marketed have a sedating 7 effect? 8 A. Most of the antidepressants that were marketed 9 at the time had sedating effects. 10 Q. Okay. In your opinion, is fluoxetine sedating? 11 A. In some individuals there have been reports of 12 sedation. 13 Q. Okay. Would it be fair to say that in the 14 majority of individuals who take fluoxetine that is not the 15 case, though? 16 A. Yes. I think that's a fair statement. 17 Q. Okay. Isn't it true that the data that you 18 presented at the 1991 -- when I say "you," I mean Lilly in 19 general -- at the 1991 advisory committee meeting showed a 20 lower incidence across the board, regardless of treatment -- 21 imipramine, fluoxetine, placebo -- than is normally found 22 within the depressed population? 23 A. Yes. 24 Q. Across the board? 25 A. Than are commonly believed, incidence of 31 1 suicide, suicidal ideation. 2 Q. Quite a bit lower? 3 A. I don't remember the magnitude, but it was 4 lower, yes. 5 Q. Less than half the percentage that is commonly 6 believed to occur in the depressed population; correct? 7 A. I don't know. Again, I don't know the 8 percentages. It wouldn't -- I wouldn't want to be quoted. 9 Q. Don't you think that's unusual? 10 A. Well, again, one has to understand the course of 11 care in a clinical trial, and the fact that they are under 12 treatment and that in the general population not all of those 13 patients may be under treatment. So I think there are lots of 14 explanations in why that could occur. 15 Q. Another factor is therapy monitored far more 16 closely than most people are in the general public that are 17 being treated with antidepressants; correct? 18 A. As part of the clinical trial they would be 19 monitored very closely. 20 Q. A lot of the clinical trials allowed for the 21 co-administration of sedatives and hypnotics and 22 benzodiazepines within the clinical trials, did they not? 23 A. Yes. 24 Q. In your opinion, would that serve to mask in a 25 lot of cases the potential stimulant profile, adverse-event 32 1 profile of fluoxetine? 2 A. I don't believe that there was ever -- that was 3 evaluated, and I don't believe there was any evidence that 4 that was the case that -- but that's, you know, remote 5 recollection. 6 Q. So you were in fact doing to a certain extent 7 what Doctor Dunner testified in his deposition -- this 8 deposition -- he does in his practice during the clinical 9 trials, were you not? 10 A. I don't think -- I don't recall the frequency, 11 but I don't believe that it was nearly as high as what he 12 suggested. 13 Q. I'm not talking about percentagewise. I mean, 14 he was, in effect, doing what was being done during the 15 clinical trials with his patients, was he not, 16 co-administering sedatives or drugs with sedatives properties? 17 A. Again, I don't know enough about what he's 18 saying, so I think it's really -- I can't confirm that that 19 was the case. There were concomitant administration of some 20 sedatives for sleep, primarily during the course of the 21 clinical trials; the frequency I don't know, but it wasn't 22 very high, as I recall. 23 Q. What was done to evaluate whether or not the 24 concomitant administration of sedatives and hypnotics and 25 benzodiazepines during the clinical trials had any effect on 33 1 the side-effect profile of fluoxetine as it showed in the 2 clinical trials? 3 A. I don't remember the details of the analysis 4 done at that time. 5 Q. Was that information presented at the 1991 6 advisory committee meeting? 7 A. Which information? 8 Q. On what was done to evaluate whether or not the 9 co-administration of those other psychotropic drugs had any 10 effect on the evaluation of fluoxetine's true side-effect 11 profile. 12 A. To my knowledge, that was not presented. 13 Q. Do you know why not? 14 A. I really don't know why not. I imagine because 15 it was really a negative finding, but that's speculation. 16 Q. Was the fact that the German government raised 17 the issue of suicidality and the use of fluoxetine discussed 18 at the committee meeting in 1991? 19 A. Which committee meeting are you referring to? 20 Q. The advisory committee meeting. 21 A. I don't remember the German situation being 22 discussed at that time. 23 Q. There were analyses done of the data bases that 24 existed in '84, and later in response to the German questions 25 on suicidality, were there not? 34 1 A. I'm sorry. Could you repeat the question again? 2 Q. Sure. You guys did an analysis of the data 3 bases that existed at the time in response to the German 4 government's questions regarding suicidality and the use of 5 fluoxetine; correct? 6 A. Yes. 7 Q. Were those analyses reduced to writing for 8 submission to the BGA? 9 A. I believe they were in response to their 10 questions. 11 Q. Okay. Wouldn't those analyses have been useful 12 or relevant, to use your word, to the 1991 advisory committee? 13 A. Well, the analysis -- there are a couple of 14 things; one is the date would have been submitted to the FDA. 15 MR. STOPHER: The data. 16 MR. NOLD: Thank you. 17 One is the data would have to be submitted to 18 the FDA. I mean, I personally can't confirm that but, again, 19 standard policy would be that all analyses that were submitted 20 to the BGA would also have been submitted to the FDA, so 21 there's never any question that the FDA knew about that. The 22 second point is that the data that was submitted to the BGA 23 would have been dated at that time because there was a much 24 larger data base from which to draw that information. So a 25 very similar analysis would have been done on the larger 35 1 population at the time of the FDA review, so I'm not sure that 2 the German data would have been terribly relevant; it was 3 included in a larger data base. 4 Q. Okay. What about if you were going -- what 5 about if you were to go to them and say, "Look, the German 6 government has analyzed the data that we provided to it and 7 has found that fluoxetine is not sedating and has suggested in 8 their package insert that we include a recommendation that in 9 some cases people who pose a suicide risk are going to have to 10 have concomitant sedatives, we would like to do that in the 11 package insert here in the United States." What do you think 12 they would say in that case? 13 A. I think it's very questionable that they would 14 let you add that to the U. S. label. 15 Q. Why? 16 A. For the reasons that I've already cited, which 17 is it recommends a concomitant medication for which there has 18 been no proof of efficacy. 19 Q. Is the Hamilton depression rating scale used in 20 and of itself to assess suicidality? 21 A. Well, it is a tool that can be used, yes. If 22 you wanted to intensely study suicidality, it probably would 23 not be the optimal tool. 24 Q. So if you're going to construct a clinical trial 25 to evaluate suicidality and the use of fluoxetine or any other 36 1 treatment, would you use the Hamilton Depression Scale -- 2 rating scale by itself without any additional rating scales or 3 any additional testing to try to evaluate whether or not 4 people are becoming suicidal or what the incidence of 5 suicidality is? 6 A. If you were going to set up a prospective study, 7 it probably wouldn't be the optimal choice. It doesn't mean 8 that it's invalid; it just means that it's not the optimal 9 choice. 10 Q. To your knowledge, has the HAM-D scale been 11 validated for rating suicidality? 12 A. I don't know what validation has taken place 13 with regards to that subitem. Obviously, the Hamilton 14 depression scales had a lot of use in assessing depression. 15 Q. There are better scales out there than the 16 HAM-D-3 question to rate suicidality, are there not? 17 A. Yes. I think there probably are, yes. 18 MR. SMITH: All right. This is the continuation 19 of the deposition of Doctor Zerbe taken on August 9th, 1994, 20 in Ann Arbor, Michigan. This is questioning beginning on 21 Page 31. 22 Was it the intent, as far as you know, of Lilly 23 that they, in submitting applications for registration of 24 Prozac in a particular country, that they would submit all 25 data to that particular country that had been submitted to the 37 1 United States Food and Drug Administration? 2 A. That's a very general question. Generally, the 3 applications were tailored to the requirements of those 4 individual countries, so it's possible there would be 5 differences in the types of data submitted, but that was 6 dictated by the regulators. 7 Q. All right. In the United States, in order to 8 secure approval of Prozac in the United States, Lilly had to 9 submit to the Food and Drug Administration data supporting 10 efficacy and safety of the product; correct? 11 A. Yes. 12 Q. And to do that, Lilly did clinical trials? 13 A. Yes. 14 Q. And there were certain of those clinical trials 15 that were deemed either by Lilly or by the Food and Drug 16 Administration as pivotal trials? 17 A. Yes. 18 Q. And those pivotal trials were trials which Lilly 19 and/or the Food and Drug Administration considered as having 20 scientific validity or following the appropriate scientific 21 method in order to establish efficacy and safety of a product; 22 correct? 23 A. Yes. 24 Q. So you knew that, as far as you were 25 concerned -- and when I say "you" I mean Lilly -- when that 38 1 data was submitted to the Food and Drug Administration, I 2 believe in September 1983 was when the IND/NDA was submitted, 3 that Lilly had what they felt was sufficient data to support 4 sufficient -- to support efficacy and safety; correct? 5 A. Yes. 6 Q. Now, my question is, would Lilly have in all 7 instances, as far as you know, submitted the pivotal trial 8 data that was submitted to the FDA to the other countries in 9 which it was requesting regulatory approval? 10 A. As far as I know, the same data were used for 11 those applications. 12 Q. Various regulatory agencies might have required 13 some additional studies or may not have looked as closely at 14 some of the U. S. pivotal trials, but that data was submitted, 15 regardless? 16 A. That would be my understanding, yes. 17 Q. For instance, we know in Germany, the German 18 regulatory agency, the BGA, wanted and requested some 19 additional European inpatient clinical trial data; correct? 20 A. Yes. 21 Q. Do you recall that? So that was a particular 22 requirement in addition to United States regulatory 23 requirements that was requested by a foreign regulatory body; 24 correct? 25 A. Yes. 39 1 Q. But the BGA had the pivotal trial data that was 2 submitted to the FDA, as far as you know? 3 A. Yes. 4 Q. And that was generally the practice in 5 submitting data to any foreign country in connection with the 6 registration process, to submit at least the United States 7 pivotal trial, clinical trial data? 8 A. Are you talking about for all drugs? 9 Q. For Prozac. 10 A. For Prozac. Because of the timing, the 11 availability of the U. S. data, I would assume that 12 information was submitted. 13 Q. You've never seen any information that the U. S. 14 pivotal clinical trial data was not submitted to any foreign 15 regulatory body? 16 A. I never saw any information -- any information 17 that would suggest it wasn't submitted. 18 Q. All right. And you generally are of the opinion 19 that, as far as you know, all U. S. pivotal trial data was 20 generally submitted in all countries? 21 A. As far as I know, although it may have been 22 presented in a somewhat different way in terms of format, 23 emphasis, et cetera. 24 Q. But the data would be presented? 25 A. In one form or another, yes. 40 1 Q. Have you ever seen any analysis of the 2 fluoxetine clinical trial data that concludes that in fact 3 Prozac is sedating and not activating? 4 A. Well, I think this suggests that in different 5 patients it can be activating and in other patients it can be 6 sedating. 7 Q. All right. And that's what you recall about the 8 clinical trial experience in connection with Prozac, is it 9 not? 10 A. Yes. 11 Q. That there were more instances of activation 12 than there were of sedation? 13 A. That's a general recollection. 14 Q. Well, it's my understanding that the clinical 15 trial data itself established that there were more patients 16 who reported activating side effects than sedating side 17 effects; is that not true? 18 A. Numerically I believe that's correct, yes. 19 Q. And that in comparing Prozac with other 20 tricyclic antidepressants, that there were more Prozac 21 patients that reported activating side effects than those 22 patients taking tricyclics; is that correct? 23 A. Again, I think numerically that's correct. 24 Q. And in connection with tricyclic antidepressants 25 versus Prozac, there were more individuals reporting sedating 41 1 side effects who were taking tricyclics than those taking 2 Prozac; is that correct? 3 A. Again, numerically I think that's what the data 4 says, yes. 5 Q. And generally that's true with respect to the 6 properties of this drug, isn't it? 7 A. I think in general, yes. 8 MR. SMITH: At this time, Your Honor, we would 9 reoffer Plaintiffs' Exhibit 71, which is Exhibit 12 to Doctor 10 Zerbe's deposition. 11 MR. MYERS: It's already in evidence, Your 12 Honor. 13 MR. SMITH: It's in evidence, but... 14 JUDGE POTTER: Okay. Pass it out to the jurors 15 and then we'll collect them up again. 16 Ladies and gentlemen, the reason we're 17 collecting them up again is you-all have got enough paperwork 18 without having duplicates of things, so that's... Also, it -- 19 well, that's one primary reason. 20 SHERIFF CECIL: (Hands document to jurors). 21 Q. Exhibit 12 has General Comments and Specific 22 Comments. You're free to read the specific comments, but my 23 questions are only going to be directed to the General 24 Comments section of Doctor Cohen's analysis. 25 A. Okay. 42 1 Q. Feel free, though, to look through the specific 2 comments, if you like. I want you to be comfortable with what 3 you're seeing. 4 A. It's hard to associate the document because I 5 don't know what they're referring to, so it probably doesn't 6 do a lot of good to look through in detail -- and detail the 7 specific comments. 8 Q. Right. Exhibit 12 is a document authored by 9 Doctor Marlene L. Cohen; correct? 10 A. Yes. 11 Q. And she's a Lilly scientist, is she not? 12 A. Yes. 13 Q. Do you personally know Doctor Cohen? 14 A. Yes. 15 Q. Do you respect her judgment as a scientist? 16 A. Yes. 17 Q. She's an individual with specific expertise in 18 brain neuropsychopharmacology, is she not? 19 A. Actually, I would not have considered Marlene an 20 expert as much in CNS pharmacology as cardiovascular 21 pharmacology; that's my recollection. Marlene was much more 22 involved in cardiovascular, as I recall. 23 Q. It was Doctor Leigh Thompson's and I believe 24 Doctor Mel Perelman's comments that Doctor Cohen had specific 25 knowledge concerning CNS neurotransmission. 43 1 A. Well, again, I wouldn't dispute their judgment, 2 per se, but that's not what -- I recall more her interest in 3 serotonin and cardiovascular. And I don't believe she was in 4 the CNS division, but I could be wrong, CNS preclinical area. 5 But maybe they're right and I'm wrong; I don't know. 6 Q. But at least she's an expert in serotonin? 7 A. Yes. She's worked a lot in serotonin. 8 Q. And it appears in Exhibit 12 she has made a 9 review of the fluoxetine safety update; correct? 10 A. Yes. 11 Q. And the safety update is what? 12 A. Well, particularly, new safety information -- 13 MR. MYERS: Periodically. 14 MR. NOLD: Thank you. 15 Well, periodically new safety information is 16 provided. I presume this is a formal safety update. I mean, 17 that could be any number of different documents, but the one 18 you're referring to would be a regulatory document updating 19 the safety -- new information generated by the safety of the 20 compound. 21 Q. Well, that's the -- the safety update is sort of 22 a term of art, meaning that it's something that's going to be 23 submitted to a regulatory agency generally; isn't that 24 correct? 25 A. That's the way I would interpret it, but safety 44 1 update is such a general term it's tough to say exactly what 2 she was referring to, but that would be my assumption. 3 Q. That it was something that was going to be 4 submitted to the Food and Drug Administration? 5 A. That would be my assumption, yes. 6 Q. Look with me at Point 8 of Doctor Cohen's review 7 of the safety data. She says there in Point 8, quote, CNS 8 stimulation, agitation and insomnia: From the data taken in 9 concert, it might appear that there is a somewhat greater 10 incidence of CNS stimulation with fluoxetine as compared with 11 placebo; for example, a greater incidence of insomnia and 12 anxiety were reported, paren, 9-95, 9-113, 9-370; agitation 13 seems pronounced, 9-160; and a decrease in REM sleep was 14 reported; and there may be a suggestion of manic psychosis, 15 9-107, 9-111. As with other antidepressant agents used in the 16 depressed population, mania and/or CNS stimulation may be a 17 minor component of the actions of fluoxetine, end quote; 18 correct? 19 A. Well, it didn't say and/or, but it said or mania 20 or CNS stimulation. 21 Q. Okay. 22 A. To me, it clearly says "or." 23 Q. Mania or CNS stimulation may be a minor 24 component of the actions of fluoxetine; correct? 25 A. Yes. 45 1 Q. Did you see this document -- 2 A. I don't recall seeing it. 3 Q. -- in your employment with Lilly? 4 A. I don't recall seeing it. 5 Q. This at least in part supports the assertions 6 set forth in Exhibit 11 in connection with the agitation, 7 activation versus sedation aspects, does it not, or fits in 8 with it? 9 A. It's compatible with that assessment, yes. 10 Q. Compatible is a good word. 11 At this time, Your Honor, we would offer 12 Plaintiffs' Exhibit 174, which was Doctor Zerbe's Exhibit 13. 13 SHERIFF CECIL: (Hands document to jurors). 14 JUDGE POTTER: Be admitted. 15 Q. Exhibit No. 13 appears to be a document authored 16 by you dated February 7th, 1990; is that correct? 17 A. Yes. 18 Q. And you were writing to apparently a physician 19 whose name has been redacted; correct? 20 A. Yes. 21 Q. Do you recall authoring this letter? 22 A. In general, yes. 23 Q. Is that your signature -- 24 A. Yes, it is. 25 Q. -- on Page 2 of the exhibit? 46 1 A. Yes. Yes, it is. 2 Q. Can you detail for me the circumstances 3 concerning your writing this letter? 4 A. Again, it's been some time ago and I really can 5 only describe it in general, but I believe it's related to the 6 Wesbecker case. 7 Q. Wesbecker? 8 A. Yes. Wesbecker case, and a query from the 9 physician involved in the case about our information on 10 violent behavior and fluoxetine. 11 Q. You say a query by a physician involved in the 12 case; which physician are you speaking of? 13 A. I don't recall the name of the physician offhand 14 and I couldn't be certain. Well, I couldn't be certain 15 exactly who it was. 16 Q. Well, Doctor Lee Coleman was Mr. Wesbecker's 17 psychiatrist. Does that name ring a bell to you as being 18 potentially -- 19 A. I don't believe it was Doctor Coleman. The name 20 is vaguely familiar, but I don't believe that's who the letter 21 was to. 22 Q. But it was -- your recollection is this Exhibit 23 13 letter dated February 7th, 1990, is a letter by you to a 24 physician involved in the Wesbecker case; is that correct? 25 A. That's my recollection. 47 1 Q. All right. Then you go on to say in the fifth 2 paragraph, "As you might imagine, violent behavior can be 3 characterized in a variety of ways. Such characterizations 4 include aggressive behaviors, self-destructive acts, including 5 suicide, and physical violence directed toward others;" 6 correct? 7 A. That's what is said, yes. 8 Q. And when you wrote this, did you write this 9 letter in coordination or assistance with Doctors Masica and 10 Heiligenstein? 11 A. Yes, I did. 12 Q. Because they are psychiatrists? 13 A. That's correct. 14 Q. And you wanted their input in how to 15 characterize violent behavior? 16 A. What I think this is referring to is the 17 apparently high number of events that were reported to the 18 FDA, and the point made was that it can be characterized in a 19 wide variety of ways. It doesn't mean that this is the ideal 20 and perfect way, but simply that that's the kind of inclusive 21 definition. 22 Q. Well, there you were including aggressive 23 behaviors and self-destructive acts, including suicide; right? 24 A. That's -- I'm not sure what you mean by I was 25 including. What I think this statement says or what it was 48 1 intended to say was that violent acts can be, in different 2 people's mind, a whole variety of things and these are some of 3 the examples, but I'm not suggesting this is sort of the ideal 4 definition. This is the kind of all-inclusive term -- set of 5 all-inclusive terms for violence. 6 Q. So it's terms used by various people at various 7 times to categorize violent-aggressive behavior? 8 A. Yes. 9 Q. And you included self-destructive acts, 10 including suicide, as one of the terms that are used by some 11 to characterize violent behavior? 12 A. That's right. 13 Q. Did you ever do anything to make any inquiry in 14 connection with the Prozac data, either the clinical trial 15 data or the data generated by the postmarketing spontaneous 16 reporting system, in connection with whether or not Prozac 17 might cause violent-aggressive behavior? 18 A. Whenever an issue like this came up, our 19 standard approach was to try to understand everything we could 20 about the specific case and to understand everything in our 21 data base related to the type of event. And part of my 22 responsibility was to see that the process was orchestrated 23 and Doctor Heiligenstein was, as I recall, central to the 24 actual data evaluation of the question of violence. 25 Q. All right. Did you ever see that data? 49 1 A. Only what Doctor Heiligenstein -- -stein 2 reported in summaries that he had, things that we had 3 summarized. I didn't look at individual cases. 4 Q. Did you look at his summary? 5 A. I think there was more than one summary, but 6 that would be -- routinely I would have looked at the 7 summaries, yes. 8 Q. What is your recollection of what those 9 summaries included? 10 A. That there was no suggestion that violence 11 occurred more frequently with fluoxetine than one would have 12 expected in the general population or even in comparable 13 trials; that the rates were the same or actually perhaps 14 lower. 15 MR. SMITH: At this time, Your Honor, we would 16 offer Plaintiffs' Exhibit 175, which is Exhibit 14 to Doctor 17 Zerbe's deposition. 18 JUDGE POTTER: Be admitted. 19 SHERIFF CECIL: (Hands document to jurors). 20 Q. Doctor Zerbe, Exhibit 14 appears to be minutes 21 of a meeting that occurred on the 18th of December, 1985; is 22 that correct? 23 A. Yes. 24 Q. It says the meeting was at DHSS. Can you tell 25 us what DHSS stands for? 50 1 A. I think it's for the Department of Health and 2 Social Services. 3 Q. Is that a regulatory body with some particular 4 country? 5 A. UK. 6 Q. England? 7 A. Yes. 8 Q. And it says the subject of that meeting is the 9 fluoxetine PL application; is that right? 10 A. Yes. 11 Q. What is PL application? 12 A. Product license. 13 Q. You were there from Lilly? 14 A. Yes. 15 Q. And there was a Doctor Wood and Fawcett there 16 from the Department of Health and Social Services in England; 17 is that right? 18 A. Yes. 19 Q. This apparently is a meeting in connection with 20 the application -- with an application by Lilly to register 21 Prozac in England; correct? 22 A. Yes. 23 Q. And that had not been granted at the time of 24 this meeting, had it not? 25 A. No. 51 1 Q. Did you author this document? 2 A. No, I didn't. 3 Q. Do you know who did? 4 A. I can't be certain. I don't know exactly who 5 authored it. 6 Q. It was somebody at Lilly, though? 7 A. Yes. I believe so. 8 Q. And were you the senior individual there from 9 Lilly at this meeting? 10 A. No. 11 Q. Who was? 12 A. Doctor Gennery was my boss. 13 Q. Who is Doctor Gennery; what was his title? 14 A. He was group medical director. 15 Q. For European affairs? 16 A. Yes. 17 Q. And you were the director of European clinical 18 investigations at that time. 19 A. That's right. 20 Q. When was Prozac finally approved for use in 21 England? 22 A. I don't recall the specific date. 23 Q. Was the application for Prozac to be marketed in 24 England ever formally rejected? 25 A. I don't believe so. 52 1 Q. That application was withdrawn for a period of 2 time, was it not? 3 A. I believe that was the case. 4 Q. Because of concerns that the Department of 5 Health and Human Services in England had raised? 6 A. That's right. 7 Q. Go with me to Page 2 of this document, toward 8 the middle of the page. It will be the fifth full paragraph 9 where it starts "with regard." Do you see that? 10 A. Yes. 11 Q. Apparently, the DHS is saying, quote, with 12 regard to the animal data, fluoxetine is perceived by the 13 authorities to cause adverse effects at much lower dosages 14 than other drugs, such as imipramine. In the long-term 15 studies there were adverse effects which caused concern, in 16 particular, liver degenerative changes and CNS toxicity, such 17 as aggression and convulsion; correct? 18 A. Yes. I mean, that's what the statement says, 19 yes. 20 Q. If you take every one of these exhibits I've 21 shown you so far this morning, we have CNS stimulation and 22 activation present, don't we, Doctor Zerbe? 23 A. The issue of CNS stimulation was one that was 24 discussed at length. Whether the conclusion was firmly 25 ingrained in anybody's mind with regard to that, I think is a 53 1 whole other matter. And the things that you've cited are 2 really pretty small items within the context of the larger 3 picture. I guess that's the only point that I would like to 4 make. 5 Q. Well, I don't know whether they're -- that's my 6 point, Doctor Zerbe. I don't know whether they're small items 7 or not. Here we have in Exhibit 15 a medical adviser in 8 Erl Wood, employed by Lilly, talking in connection with a 9 world-renowned toxicologist, don't we? 10 A. Yes. 11 Q. And that medical adviser or the world-renowned 12 toxicologist is saying we must emphasize that the side effects 13 of fluoxetine are related to its pharmacology; i.e., CNS 14 stimulation. Correct? I mean, it's there in black and white, 15 isn't it? 16 A. Yes. But I think that that's taken out of 17 context with regard to the whole document. The document 18 itself -- the expert was not called in to evaluate the issue 19 of stimulation or the CNS pharmacology. The toxicologist was 20 called in to look at phospholipidosis. And virtually the 21 whole document, except for that almost parenthetic statement, 22 is related to phospholipidosis. It's not related to that 23 point. 24 Q. Is it parenthetic when it says, "Here we must 25 emphasize that the side-effect profile -- side effects of 54 1 fluoxetine are related to its pharmacology"? That doesn't 2 look parenthetic to me, Doctor, when he's talking about how 3 you emphasize something with respect to a regulatory body and 4 with respect to a property of a medication that's now being 5 taken by ten million people, is it? 6 A. Technically it's not in parentheses, but it does 7 say, that is -- I want to read it correctly -- that is, CNS 8 stipulation, et cetera. You know, it was almost a throw-away 9 comment as I read it. 10 Q. That's your interpretation. 11 A. That's my interpretation; that's right. 12 Q. Whether or not somebody would consider that a 13 throw-away comment would have to take these other documents 14 into consideration also, wouldn't they? Well, Doctor Zerbe, 15 do you have an opinion in connection with whether or not 16 Prozac is CNS stimulating? 17 A. My view is that it is not sedating or not 18 predominantly sedating, I guess is the way I would summarize 19 it, as opposed to truly stimulating, but that's my opinion. 20 Q. Do you have an opinion concerning whether or not 21 Prozac is CNS activating? 22 A. I'm not sure how you define CNS activating. 23 Q. Let's define it as it's defined by Doctor 24 Beasley or Doctor Heiligenstein in their Exhibit 11 in their 25 activation sedation paper, where it compares it to a placebo 55 1 and other tricyclics and finds there are more instances of CNS 2 activation. 3 A. Well, I can't dispute those figures. So, I 4 mean, activation as defined as they have done it numerically 5 is higher. Again, in this document, I had trouble linking the 6 statistics to the figures but... 7 Q. All right. 8 MR. SMITH: Your Honor, the next document was 9 Exhibit 16 to Doctor Zerbe's deposition, which has already 10 been admitted into evidence as Plaintiffs' Exhibit 87. We 11 have copies of that that we'd like to pass out to the jurors 12 for their consideration in connection with the following 13 testimony. 14 SHERIFF CECIL: (Hands document to jurors). 15 Q. Doctor Zerbe, Exhibit 16 is three pages of Eli 16 Lilly E-mail dated September 13th and 14th, 1990, is it not? 17 A. Yes. 18 Q. And you're copied under the September 14th, 7:31 19 listing, are you not? 20 A. Yes. 21 Q. It appears that the top part of Exhibit 16 is an 22 E-mail authored by Doctor Leigh Thompson; is that right? 23 A. Yes. 24 Q. Directed to yourself and others; is that right? 25 A. Yes. 56 1 Q. Okay. So you knew in advance Doctor Leigh 2 Thompson was going to make a presentation to the board of 3 directors concerning suicidality? 4 A. Again, I don't know how much in advance. We may 5 have only known on Monday or shortly before the time that he 6 was going to do it; that it was -- that it was -- that this 7 was requested. 8 Q. All right. And you delegated the physical 9 looking at the data and looking at the presentation he was 10 going to be making to the psychiatrists who worked under you? 11 A. Yes. 12 Q. Then apparently Doctor Heiligenstein is 13 reporting in the balance of this exhibit what he, Doctor 14 Beasley and Doctor Wheadon had concluded in reviewing the data 15 -- or reviewing the data that was to be presented to the 16 board; is that right? 17 A. That's the way I read it, yes. 18 Q. Doctor Heiligenstein says that, under Verbatim 4 19 at the bottom of Page 1, quote, we feel that caution should be 20 exercised in the statement that suicidality and hostile acts 21 in patients taking Prozac reflect the patient's disorder and 22 not a causal relationship to Prozac, end quote; correct? 23 A. That's right. 24 Q. Doctor Heiligenstein goes on to say, 25 postmarketing reports are increasingly fuzzy, and we have 57 1 assigned, "yes, reasonably related," on several reports; 2 correct? 3 A. Yes. 4 Q. Now, you're not copied on this particular 5 portion of Exhibit 16, are you? 6 A. No. 7 Q. Apparently the psychiatrists are reporting 8 directly back to Doctor Thompson. 9 A. Yes. That would appear to be the case, yes. 10 Q. Have you ever seen Exhibit 16 before? 11 A. I don't recall seeing it, but I obviously would 12 have as, you know, part of this having been copied. 13 Q. Well, the point is, you weren't copied. 14 A. Well, when it's printed out, the forwarding 15 message would be copied, so when Leigh's message came to me, 16 I would have had the whole thing. 17 Q. Okay. All right. So you are copied in the 18 latter transmission, so he would have pulled up the 19 transmission from Doctor Heiligenstein directly to Doctor 20 Thompson; is that right? 21 A. Yes. That's right. 22 Q. Did you talk with any of the psychiatrists under 23 your supervision once you got this memo? 24 A. We were, you know, continually talking, so it's 25 hard to say what -- how this specific memo came into our 58 1 conversation. But we would have talked to them, you know, 2 literally daily regarding this issue at this particular point. 3 Q. Well, did you agree with the psychiatrists at 4 Lilly where they say, "We feel that caution should be 5 exercised in a statement that, quote, suicidality and hostile 6 acts in patients taking Prozac reflect the patient's disorder 7 and not a causal relationship to PZ, meaning Prozac," end 8 quote? 9 A. Well, I think worded in that way I would agree 10 with it. I think our position always was we wanted to be 11 cautious; we wanted to be sure that the data we had and were 12 presenting was accurate. And so I think this was a period 13 when the psychiatrists were very cautious, very probing, 14 trying to be sure that we really understood the event and what 15 data we had. So I supported them in that kind of a position, 16 that is, exercising caution. We still hadn't reached a 17 conclusion about what the wording should be, but certainly it 18 was advisable to exercise caution. 19 Q. Well, what the psychiatrists are saying, Doctor 20 Zerbe, is that Doctor Thompson exercise caution when you tell 21 the board of directors at Eli Lilly and Company that 22 suicidality and hostile acts are related to the patient's 23 condition as opposed to Prozac itself, isn't it? 24 A. Well, that's what they're saying. Based on the 25 knowledge at that particular point in time -- 59 1 Q. September 13th. 2 A. -- our advice as the psychiatric group should be 3 that you should exercise caution in, you know, a verbatim that 4 totally discounts this issue. And not all the information was 5 available at that particular point, and so caution was 6 appropriate. 7 Q. What information was available was -- was -- 8 they go on to explain, don't they? They say postmarketing 9 reports were increasingly fuzzy and we have assigned "yes, 10 reasonably related" on several reports; correct? 11 A. That's what they say, yes. 12 Q. What they're speaking of is postmarketing 13 reports of suicidality and hostility, aren't they? 14 A. I assume. I don't know that this explicitly 15 states that, but -- it doesn't explicitly state that. 16 Q. That's the subject, isn't it? 17 A. That's the subject, yes. 18 Q. It's not talking about nausea or skin rash, is 19 it? 20 A. No. 21 Q. The presentation to the board of directors is 22 going to have to do with suicidality and hostile acts, isn't 23 it? 24 A. I'm not sure that the presentation was confined 25 to that; I just don't know exactly. But that's certainly on 60 1 point, Verbatim No. 4 is the topic. 2 Q. That's the topic, being suicidality and hostile 3 acts; correct? 4 A. Yes. 5 Q. And what Doctor Heiligenstein goes ahead and 6 says there is, that we've been getting reports of suicidality 7 and hostility and that we've assigned, "yes, reasonably 8 related," on several of these reports; correct? 9 A. That's what he said, yes. 10 Q. Did you know that at the time? 11 A. Well, I mean, I would have known it as a result 12 of ongoing discussions that some of those events may be 13 classified as "yes, reasonably related." That was always up 14 to the physician. And we never -- you know, we never 15 questioned or argued about that point. But that does not mean 16 that they're conclusively related and that's an important 17 point. It just means that other alternative explanations at 18 the point of which the box was checked were not evident. 19 Q. When you say "we left this up to the 20 physicians," what are you talking about? 21 A. About the psychiatrists working with, you know, 22 the physicians that reported. You know, the management didn't 23 second-guess those things and go back and say, you know, why 24 did you put this as possibly related. 25 Q. The point is, is that the people who were 61 1 checking "yes, reasonably related," were Doctor Heiligenstein, 2 Doctor Beasley and Doctor Wheadon, weren't they, because they 3 were the psychiatrists reviewing the reports? 4 A. Yes. I assume it was them. It may have been 5 someone else working within that division, but basically they 6 would have been consulted on the -- 7 Q. But it was the Lilly employees, the Lilly 8 psychiatrists, the Lilly experts who were checking "yes, 9 reasonably related;" correct? 10 A. That's right. 11 Q. And it was their job, the Lilly experts, the 12 Lilly psychiatrists, to investigate reports of suicidality and 13 hostility, wasn't it? 14 A. Yes. That was one of their responsibilities, 15 yes. 16 Q. They were charged with monitoring adverse events 17 in connection with Prozac, weren't they? 18 A. Yes. 19 Q. And it was their responsibility to investigate 20 adverse events in connection with Prozac, wasn't it? 21 A. Yes. 22 Q. And they were to contact physicians or reporters 23 of suicidality and hostility, weren't they? 24 A. When possible, yes. 25 Q. And make an investigation concerning whether or 62 1 not suicidality and hostility were related to Prozac, weren't 2 they? 3 A. That, in collaboration with other outside 4 investigators, yes. 5 Q. And with respect to particular instances, on 6 occasion they would make a determination concerning whether or 7 not the instances of suicidality or hostility were reasonably 8 related to the use of the drug; correct? 9 A. They would make those assessments based on their 10 knowledge at that particular point. 11 Q. Yes. Of that particular case. 12 A. Of that particular case. 13 Q. In other words, they weren't making a 14 statistical analysis in connection with particular cases, were 15 they? 16 A. Well, not for this, the purpose of this, no. 17 Q. They were making a factual analysis of the facts 18 that occurred in a particular case, weren't they? 19 A. I'm not sure. I mean, you -- you can -- you can 20 call it factual analysis, but the reality is that they were 21 operating frequently on very limited information. 22 Q. And sometimes very specific detailed 23 information, weren't they? 24 A. Sometimes. 25 Q. But they were making -- 63 1 A. In most of the cases in which -- well, in 2 general, the sort of operative rule was if there was a 3 question, then it was included in that category. 4 Q. Well -- 5 A. And therefore, when there was a lack of 6 information, it tended to be listed as, you know, reasonably 7 possibly related. We were very concerned about any perception 8 that we were hiding information. 9 Q. Let's talk about that. Let's talk about that. 10 Doctors Beasley, Heiligenstein and Wheadon were charged with 11 the responsibility in the psychiatric area, because they were 12 psychiatrists, of reviewing instances of adverse psychiatric 13 reports in connection with the use of Prozac; correct? 14 A. Yes. 15 Q. And they were charged with investigating reports 16 of particular instances where the issue was this adverse 17 reaction of suicide, suicidal ideation, or hostility related 18 to the use of Prozac, weren't they? 19 A. Well, possibly related to the use of Prozac. 20 Q. Reasonably possibly related? 21 A. Reasonably possibly related. 22 Q. And what they were supposed to do was get all 23 information available to them concerning a particular case, 24 weren't they? 25 A. Within their capabilities. 64 1 Q. Sometimes it was they were able to, sometimes 2 they weren't able to get all information? 3 A. That's correct. 4 Q. But they were expected to use whatever means was 5 necessary to get as much information as possibly existed at 6 the time? 7 A. To understand the event as best they possibly 8 could. I think that's a fair summary. 9 Q. In other words, they were expected to and did on 10 occasion talk with the treating physician? 11 A. Yes. 12 Q. They were expected to and did on occasion obtain 13 medical records? 14 A. Yes. 15 Q. They were expected to and did on occasion talk 16 with nurses and family personnel? 17 A. Right. 18 Q. They were expected to and did on occasions -- 19 A. I'm not sure how often they talked to families. 20 Q. If that was reasonable to do and it was 21 possible, they would -- they were to do that, weren't they? 22 A. I think if your point is that they would attempt 23 to thoroughly understand those events, they -- that was part 24 of their responsibility, to try to thoroughly understand the 25 events. 65 1 Q. Right. 2 A. But it was not always possible. 3 Q. I understand that in some instances you may have 4 a lot of information and in some instances you wouldn't have 5 as much information. 6 A. Right. 7 Q. But whether you had information or not, they 8 were charged to secure as much information as possible? 9 A. That's right. 10 Q. In other words, we'll get to some documents, but 11 the issue of Prozac and suicidality was one that was of great 12 concern to the management and Eli Lilly; correct? 13 A. Yes. 14 Q. And there wasn't supposed to be any stone left 15 unturned in examining this issue, was there, in September of 16 1990? 17 A. That's right. 18 Q. And these psychiatrists, these Lilly employees, 19 were expected to get as much information as is possible about 20 a particular instance; correct? 21 A. I mean, I think I've answered that question. 22 They are trying to get all they can about it but they don't 23 always have that. 24 Q. I understand that. But they always are expected 25 to get as much as is possible? 66 1 A. I think that's fair to say, yes. 2 Q. These are also psychiatrists that are employed 3 by Eli Lilly and Company because they're supposedly reasonably 4 intelligent individuals? 5 A. Sure. 6 Q. And you as their indirect supervisor did indeed 7 have respect for their medical judgments, did you not? 8 A. Yes. 9 Q. You don't know of any instances where any of 10 these individuals -- Doctor Beasley, Doctor Wheadon or Doctor 11 Heiligenstein -- exercised poor medical judgment, do you? 12 A. Well, I can't think of any at the moment, no. 13 Q. If you had seen that, you would have issued some 14 type of criticism of them, would you not? 15 A. Well, yes. 16 Q. Did you ever complain to Doctor Masica, their 17 direct supervisor, concerning any instances of poor medical 18 judgment that you had seen in Doctor Beasley, Wheadon or 19 Heiligenstein? 20 A. Well, I mean, I'm not sure what you would -- I'm 21 not sure you would call it poor medical judgment. I think, 22 you know, all of us would look at the same set of data and we 23 may reach different conclusions. 24 Q. I'm not talking about data; I'm talking about 25 their integrity as medical doctors. 67 1 A. I never questioned their integrity. 2 Q. I'm talking about their ability to exercise 3 their profession and their subspecialty as psychiatrists, you 4 respect their judgment as psychiatrists? 5 A. I never questioned their expertise. 6 Q. Would you feel uncomfortable if you had a 7 psychiatric problem in going to any one of these individuals 8 for advice concerning your psychiatric problems? 9 A. I don't believe so. 10 Q. All right. Wasn't it part of their duty, then, 11 to exercise judgment as psychiatrists, based on their medical 12 knowledge and background, concerning whether or not these 13 reported adverse events of suicide and hostility were related 14 to Prozac? 15 A. I'm sorry. Could you repeat the question? 16 Q. Well, within their -- read it back. 17 MR. NOLD: The question was read back. 18 Well, within the limitations of the data they 19 had available, and many times they did not have despite their 20 efforts a great deal of information, so it was not -- there 21 was not a whole lot of psychiatric judgment involved. It was 22 more a matter of, you know, bureaucratically they were left by 23 default to put it into a possibly-related category. I just 24 don't know enough about -- your implication I believe is that 25 they examined it and reached the conclusion that they were 68 1 reasonably possibly related. 2 Q. The reason I say that is because Doctor 3 Heiligenstein, Doctor Wheadon and Doctor Beasley have all 4 three testified that's exactly what they did on many 5 instances. 6 A. I can't judge that. All I'm saying is there may 7 have been some of these and the fuzziness may have been 8 related to the fact that they didn't have information. And if 9 you have the testimony from Doctor Beasley, you're asking me 10 to speculate about what was in their mind, and I'm not the 11 best person to do that. 12 Q. You're certainly not going to give us sworn 13 testimony today, Doctor Zerbe, are you, that what they're 14 doing is checking "yes, reasonably related" only in instances 15 where they didn't have any information or scant information, 16 is it? 17 A. Well, I just don't know. I don't know which 18 ones were reasonably possibly... 19 Q. Why would you make such a statement that you 20 suspect or that there were many instances where we didn't have 21 any information so they may have put it in that category of 22 "yes, reasonably related"? 23 A. I mean, again, if you've got Doctor Beasley and 24 that group saying that they looked at the cases and they 25 thoroughly evaluated them and reached the conclusion that they 69 1 were reasonably possibly related, then that probably is much 2 more valid than my speculation about what they looked at. I 3 mean, that's the only point that I would make. 4 Q. Would that be a surprise to you, Doctor, that 5 Doctor Wheadon has testified, for instance, that he 6 categorized at least 80 reports of suicidality and hostility 7 and violent-aggressive behavior as being reasonably possibly 8 related to the use of Prozac? Would that surprise you? 9 A. I guess it really wouldn't surprise me. 10 Q. Doctor Wheadon was one of the psychiatrists that 11 was charged with the responsibility of investigating these 12 instances of suicidality and hostility, wasn't he? 13 A. Doctor Wheadon was one of the physicians, yes. 14 Q. Go with me to Page 2, where it appears about 15 Page 5 of the verbatims. Do you see that? 16 A. Yes. 17 Q. Right above the top of that it says, Page 5, 18 under Suicidal Thinking in Clinical Trials, "You may want to 19 note that the trials were not intended to address issues of 20 suicidality." Also, in Paragraph 2, "Patients were excluded 21 that were serious suicidal risk." Do you see that? 22 A. Yes. 23 Q. That word is kind of fuzzy but it is "risk." Do 24 you agree, Doctor Zerbe, that the clinical trials as of 25 September 14th, 1990, done in connection with the use of 70 1 Prozac, were not intended to address the issue of suicidality? 2 A. Well, not directly. They were not intended to 3 assess the suicidality, per se. There were aspects of the 4 trials that allowed an evaluation of suicidality. 5 Q. Listen to my question. Do you agree with Doctor 6 Heiligenstein's statement there that, quote, trials were not 7 intended to address issue of suicidality, end quote? That's a 8 yes or no. 9 A. Well, is it yes or no? I agree only partially 10 with that statement. There are ways -- you know, as 11 suicidality is part of the disease, the trials were intended 12 to assess suicidality -- 13 Q. So you don't agree with it? 14 A. -- as part of the disease. 15 Q. What part do you agree with and what part do you 16 disagree with? 17 A. If the implication of the statement is that you 18 can't assess suicidality, then I disagree with it. If the 19 implication is that we had specific scales to look at 20 suicidality, per se, then I agree with it. Do you understand 21 what I'm saying? One is able to assess suicidality as part of 22 the disease of depression from the trials that were done. 23 Q. All right. Okay. And I believe you've already 24 testified in your deposition previously that the HAM-D Item 3 25 suicidality item on that scale was not a sophisticated scale 71 1 and that there were better scales to measure suicidality, in 2 your opinion? 3 A. Yes. And I still agree with that statement. 4 Q. My reading of this statement is simply, Doctor 5 Zerbe, that the trials were not intended to assess 6 suicidality? 7 A. Well, only -- I mean, suicidality is part of 8 depression. They were intended to address the issue of 9 depression and therefore in a sense they were intended to 10 address suicidality as part of depression. That's the 11 problem. That's why I would disagree with the statement. 12 Q. What would be the marketing value of that? 13 MR. MYERS: Excuse me, Your Honor. 14 I think you omitted something, Mr. Smith. 15 MR. SMITH: Well, I couldn't tell. We didn't 16 make any black lines and it was green lines, and I didn't know 17 whether to read the black lines or the green lines. 18 JUDGE POTTER: I tell you what, ladies and 19 gentlemen of the jury. We're not going to take a break, but 20 why don't you-all just stand up for a minute. 21 You can back up a question or two, if you want 22 to. 23 MR. SMITH: All right. Why don't we start again 24 on Page 116, Bill, at Line 17. 25 MR. NOLD: Okay. 72 1 Q. My reading of this statement is simply, Doctor 2 Zerbe, that the trials were not intended to assess 3 suicidality. 4 A. Well, only -- I mean, suicidality is part of 5 depression. They were intended to address the issue of 6 depression and, therefore, in a sense they were intended to 7 address suicidality as part of depression. That's the 8 problem. That's why I would disagree with the statement. 9 Q. Then tell us, as a member of senior management, 10 if the trials were intended to address suicidality, why there 11 wasn't a better determination and examination made of the 12 issue of suicide in connection with the clinical trials. 13 A. I think you're misstating what I stated. My 14 disagreement with this is that if you consider suicidality as 15 part of depression. 16 Q. I don't consider it a part of depression in 17 every instance. There's millions of people who are depressed 18 who are not suicidal, aren't there? 19 A. Yes. But are you going to let me finish my 20 general statement? 21 Q. Yes. 22 A. If you consider suicidality as part of the 23 spectrum of depression, okay, then the trials were designed to 24 thoroughly evaluate depression and suicidality as part of it, 25 in the garden variety, you know. On the other hand, it was 73 1 not a trial designated to look at suicide, per se. And if 2 that's what the meaning of this statement, then I agree with 3 the author. If they're excluding it that the trials were 4 invalid for some assessment of suicide in some way, maybe less 5 refined way but still a valid way, then I disagree with the 6 statement. 7 Q. What would be the marketing value of that, 8 combining an antidepressant such as Prozac with a 9 tranquilizer? 10 A. I think there was a view perhaps at one point 11 that the sedative effects of the tricyclics which weren't 12 present with fluoxetine early in the treatment were perceived 13 by physicians as something positive. 14 Q. All right. 15 A. And that by combining a tranquilizer, one could 16 mimic those early effects of the tricyclics. 17 Q. All right. 18 A. I think that was the marketing angle. 19 Q. Was it also a scientific consideration, also? 20 A. Well, I mean, certainly scientifically one could 21 mimic the effects of tricyclics, but I don't think from a 22 medical perspective it was viewed as something that was very 23 critical or very important. 24 Q. The reason I ask that is because early on in the 25 clinical trials, back as early as 1978, Doctor I. H. Slater, 74 1 one of the original medical monitors in connection with this 2 drug, reflected that there was an issue early on as to whether 3 or not it might be of benefit to have Prozac plus a 4 tranquilizer or benzodiazepine together, marketing squeezed 5 together in one pill -- that's S-Q-U-U-Z-E-D -- you know, 6 combined in one pill back as early as '78, '79, when Doctor 7 Slater was analyzing it. Had you heard that raised before? 8 A. I had never heard that Doctor Slater had 9 proposed that, no. 10 Q. And the feeling was that since Prozac didn't 11 have a generally sedating effect, such as the tricyclic 12 antidepressants did, that it might be of some benefit to 13 combine a tranquilizer to get that initial tranquilizing 14 sedating effect, since Prozac didn't possess that property. 15 Would that be accurate? 16 A. I think the question that came up was, was that 17 something of importance, and that's what was being proposed as 18 a question. 19 Q. Was the thought to actually add with the Prozac 20 in the preparation some tranquilizing agent, or was it to 21 prescribe an additional pill that you would take along with 22 Prozac? 23 A. I think the proposal that's being discussed here 24 is more some combination medication. 25 Q. You mean in one pill? 75 1 A. In one pill. 2 Q. Now, if I were a physician and a patient came to 3 me, I could certainly prescribe a combination of medications 4 to treat a particular illness, could I not? 5 A. Yes. 6 Q. For instance, if a patient came to me with a 7 cold, I could prescribe aspirin as one ingredient and a 8 specific antihistamine as another agreed; right? 9 A. Yes. 10 Q. Two pills? 11 A. Yes. 12 Q. And there's no prohibition against a physician 13 prescribing those two ingredients in combination, is there? 14 A. That's correct. 15 Q. And the physician doesn't have to go out and do 16 a clinical trial to demonstrate efficacy of the combination of 17 those two ingredients, does he? 18 A. No. 19 Q. And that combination of ingredients that the 20 physician may have prescribed for that patient may be more 21 efficacious in treating that cold that that patient had; 22 right? 23 A. Yes. 24 Q. Because the patient may have had a number of 25 symptoms; the patient may have had a headache and achiness on 76 1 one hand, which could be alleviated by the aspirin; correct? 2 A. Yes. 3 Q. And the patient may have had a runny nose and 4 sneezing, which could be alleviated with the antihistamine; 5 correct? 6 A. That's right. 7 Q. Doctors do that every day, don't they? 8 A. Yes. 9 Q. Combine medications for treatment of a 10 particular illness that has a variety of symptoms, don't they? 11 A. Yes. 12 Q. All right. Then I'll ask you this question: 13 What is it about the tricyclics' pharmacology that gives them 14 a sedating property? 15 A. I think it's related to the anticholinergic 16 effects that the tricyclics have. 17 Q. What do you mean by anticholinergic effects? 18 A. Blocks cholinergic receptors. 19 Q. What are cholinergic receptors? 20 A. They are another type of receptor that responds 21 to acetylcholine and acetebocholine. That's not close. 22 MR. STOPHER: It's acetylcholine. 23 Q. So what you're saying -- 24 MR. NOLD: What's the other one? 25 MR. STOPHER: Acetebocholine. Acetylcholine or 77 1 acetebocholine. 2 JUDGE POTTER: Go ahead, Mr. Smith. 3 Q. So what you're saying is that Prozac and the 4 tricyclics work on different sets of receptors? 5 A. Yes. 6 Q. What I'm saying is -- 7 MR. STOPHER: No. That's you, Bill. 8 A. What I'm saying is that Prozac does not have the 9 same spectrum of effects on different receptors that 10 tricyclics do. Prozac is much more specific for the serotonin 11 reuptake mechanism, whereas tricyclics have a wider variety of 12 effects on different neurotransmitters and reuptake 13 mechanisms. 14 Q. Which makes them more likely to produce sedation 15 and makes Prozac less likely to produce sedation? 16 A. That's right. 17 Q. By virtue of the fact that the tricyclics affect 18 a variety of receptors and Prozac only affects the serotonin 19 reuptake receptors; is that correct? 20 A. Yes. 21 Q. And both produce separate -- in that instance 22 produce separate and distinct physiological responses by 23 virtue of separate and distinct actions on different 24 receptors; is that what you're saying? 25 A. That's right. 78 1 MR. SMITH: At this time, Your Honor, we would 2 offer Plaintiffs' Exhibit 176, which was Exhibit 26 to Doctor 3 Zerbe's deposition. 4 JUDGE POTTER: Be admitted. 5 SHERIFF CECIL: (Hands document to jurors). 6 Q. Doctor Zerbe, Exhibit No. 26 apparently is 7 reflective of a meeting concerning fluoxetine in the UK 8 authored by Doctor or Mr. A. D. J. Brockwell; correct? 9 A. Yes. 10 Q. You're copied on this memo; correct? 11 A. Yes. 12 Q. It has to do with questions that have been 13 raised by the CSM, which is what, the British counterpart to 14 the U. S. FDA? 15 A. Yes. 16 Q. What is it, Committee for Safety in Medicine? 17 A. Yes. 18 Q. Apparently in 1985, on the bottom of Page 2 of 19 this document, the CSM raised a question, Question No. 5 20 being, quote, clarification of comparative drugs is also 21 required. 22 MR. STOPHER: Groups. 23 Q. -- groups is also required. Dose relationships 24 are difficult to demonstrate in the early clinical studies 25 because of the dose escalation that was used. Preliminary 79 1 data from the fixed-dose studies, however, does suggest a dose 2 relationship for some of the adverse events, end quote; 3 correct? 4 A. Yes. 5 Q. And the action there was pending clarification; 6 correct? 7 A. Yes. 8 Q. Do you recall this document or this memo? 9 A. No, I really don't. 10 Q. Do you recall that the British government's 11 review of the data had indicated that -- indicated that there 12 might be a suggestion of a dose relationship for some of the 13 adverse events? 14 A. I don't think that's what this memo says, but I 15 don't recall that at this particular point. 16 Q. Did I read it incorrectly? 17 A. The way I read it, it says the dose 18 relationships are difficult to demonstrate in early clinical 19 studies because of the dose escalation that was used. That 20 was the CSM piece. And then I think that David Brockwell is 21 saying is preliminary data from the fixed-dose study, however, 22 does suggest a dose relationship for some of the adverse 23 events. It's almost like -- the way I read it is it's almost 24 like an action item, that the issue of dose -- we've got some 25 preliminary data to address that point. That's kind of the 80 1 way I read it. I don't think the CSM would have even had the 2 preliminary data from the fixed-dose study. That's why I 3 question whether it's the CSM asking this. 4 Q. It's all phrased under CSM Question No. 5, isn't 5 it? 6 A. I understand what you're saying. I'm just 7 telling you how I read this statement or read this -- yes, 8 it's a statement. 9 MR. SMITH: Your Honor, at this time, we would 10 point to the jury Plaintiffs' Exhibit 177, which has been 11 previously admitted into evidence, which is now Zerbe 12 Exhibit 28. 13 JUDGE POTTER: This one is already entered as 14 74? 15 MR. SMITH: Yeah, whatever the sticker says. 16 JUDGE POTTER: Right. 17 SHERIFF CECIL: (Hands document to jurors). 18 Q. Exhibit 28 is a two-part document, but I stapled 19 the first page to it just to give you an idea of when it was 20 transmitted. Well, you are copied on Page 1 of the memo 21 authored by Doctor Lange, are you not? 22 A. Yes. 23 Q. Or Mr. Lange? 24 A. Yes. 25 Q. Then Page 2 and 3 have to do with registration 81 1 -- registering Prozac in the United Kingdom, England, in a 2 10-milligram formulation; correct? 3 A. Yes. 4 Q. Ten-milligram solid formulation; is that right? 5 A. Yes. 6 Q. Now, as a little background, Lilly had for some 7 time prior to March 21st, 1991, manufactured Prozac in a 8 liquid form, had they not? 9 A. I don't know the exact date for liquid. My 10 recollection would have been it was later than 1991. 11 Q. Okay. Well, you may be right. Then are you 12 saying at the time that this document was authored in March of 13 1991, that there may not have been anything in existence other 14 than the 20-milligram solid formulation? 15 A. That's right. 16 Q. Now, let me ask you this, also. Is 20 17 milligrams of Prozac twice as much as 10 milligrams of Prozac 18 in quantity? 19 A. I'm looking for the trick in the question, but, 20 yes, it's twice as much. 21 Q. Is it twice as potent as 10 milligrams? 22 A. I'm not sure that I really -- it's tough to 23 answer the question. I don't know what you mean by twice as 24 potent. 25 Q. Should it have twice as much potential to bind 82 1 to serotonin reuptake receptors to increase presence of 2 serotonin in the synaptic cleft? 3 A. I don't think you can reach that simple 4 conclusion from what you've said. 5 Q. Why can't I get there? 6 A. Well, because the binding to it may be affected 7 by the concentrations that are already there, so you don't 8 actually get twice as much binding; you may only get a quarter 9 of as much binding. And there certainly is a limit to the 10 linear area in relationship, but I don't think you can say 11 that 20 has twice as much effect as 10 or et cetera. 12 Q. Can you say that 40 has twice as much as 20? 13 A. No. You really can't reach that conclusion, I 14 don't believe. 15 Q. Can you say 80 has twice as much as 40 binding 16 properties? 17 A. Well, again, I'm not sure what you mean by 18 binding properties. 19 Q. I thought what Prozac did was it got up there in 20 the receptors that ordinarily would reuptake serotonin from 21 the synaptic cleft and competed there for the serotonin 22 molecules and made it less likely that the serotonin would be 23 reuptake at the receptor site. In other words, Prozac 24 actually occupies a space on the serotonin reuptake receptor; 25 is that incorrect? 83 1 A. Well, I don't know. In general that's not 2 incorrect. 3 Q. All right. And I'm not saying -- 4 A. But what I'm saying is that it's not necessarily 5 a linear relationship. 6 Q. That's what I'm trying -- of course, maybe these 7 questions should be directed to Doctor Fuller or somebody 8 that's more familiar with neuropsychopharmacology or biology 9 than yourself. But as a general proposition, could it be said 10 that you should have an increase, an increase in serotonin 11 reuptake greater at 20 than at 10? 12 A. Well, in general, there tends to be a 13 dose/response relationship. 14 Q. Okay. 15 A. In general, the higher dose produces a more 16 pharmacologic effect. 17 Q. Okay. 18 A. But that's not true in all cases nor with all 19 medications. 20 Q. We're talking about Prozac and what has been 21 established in the Prozac clinical trial experience. 22 A. Okay. That wasn't clear. I thought you were 23 talking more generally in pharmacology. But I think the 24 general statement still holds within the dose range of 20, 40, 25 60, at least based on the fixed-dose study clinically, that 84 1 there are -- that there's more of an effect, not necessarily 2 twice as much, but more. 3 Q. Was there any biological study done to measure 4 whether or not it was twice the effect? 5 A. I don't believe so. 6 Q. But the hypothesis is that more should be more 7 and less should be less? 8 A. Within some limits. I mean, dose ranges aren't 9 infinite. There's a limit to the extrapolation of that. 10 Q. All right. But within limits it could be said 11 more equals more effect, less equals less effect? 12 A. In general. 13 Q. All right. Apparently there was discussions of 14 whether to have solid forms of Prozac in 20 milligrams; 15 correct? 16 A. Yes. 17 Q. And there was a discussion in connection with 18 both the regulatory and the psychiatric standpoint? 19 A. Yes. 20 Q. It says, "We worked closely with the Medicines 21 Control Agency, MCA, in late '90, '91. In discussions with 22 myself and David Wheadon in November, Doctor Sue Wood, head of 23 MCA's safety monitoring, expressed 3 MCA priorities for 24 Prozac;" right? 25 A. Yes, sir. 85 1 Q. Item C was Introduction of Lower Prozac Dose; 2 correct? 3 A. Yes. 4 Q. So can I assume that in March of 1991, Prozac 5 had been approved in England but it was only available in the 6 20-milligram solid dosage form? 7 A. Yes. 8 Q. It said the need for C, which is Introduction of 9 Lower Prozac Dose, has been strongly reinforced by Doctor Wood 10 and others in her group on several subsequent occasions, 11 including the suggestion that I provide a written statement of 12 Lilly policy in timing in this area. And then he puts in 13 parentheses, not done, close parentheses; correct? 14 A. Yes. 15 Q. It says they believe this is necessary because 16 alternate-day dosing recommended in some patients may reduce 17 compliance? 18 A. Yes. 19 Q. So is alternate-day dosing a situation where the 20 physician says take 20 milligrams on Monday, Wednesday and 21 Friday? 22 A. Every other day, basically every other day. 23 Whether that's how we recommended it, I don't know, but every 24 other day. 25 Q. And from a medical standpoint there's some 86 1 drawbacks to that, is there not? 2 A. There are drawbacks from the perspective of 3 compliance, yes. 4 Q. When you say from the perspective of compliance, 5 yes? 6 A. It means more difficult for patients to remember 7 to take their dose every other day as opposed to every day. 8 Q. So the physician is going to be better assured 9 that the patient is consuming their medications as directed if 10 they directed to do this on a more regular basis, which would 11 be every day, take in every morning? 12 A. I think again in general, yes. It's probably 13 better to get compliance every day, once a day, than every 14 other day. 15 Q. All right. Item B there is that 5-milligram 16 data interpreted as showing efficacy, correct? 17 A. Yes. 18 Q. Do you agree that the 5-milligram data showed 19 efficacy? 20 A. In the trials done, five milligrams was 21 statistically better than placebo. 22 Q. Therefore, efficacious in treating depression? 23 A. Yes. 24 Q. C, it says relatively large numbers of 25 Lilly-supplied events and UK yellow-card reports may be 87 1 reduced if 10-milligram dose used in some patients; correct? 2 A. That's what it says, yes. 3 Q. Now, that goes back to the yellow cards that you 4 were talking about earlier, which is a notice in England of an 5 adverse event in connection with Prozac; right? 6 A. Yes. It's a more formal follow-up system than 7 spontaneous adverse events. 8 Q. Is there a requirement for a yellow-card 9 analysis in England that there be some investigation as to 10 causal relationship between the event complained of and the 11 drug? 12 A. I really don't remember how that's worded within 13 the yellow-card system, whether it's any event or whether it's 14 only causally -- events believed to be causally related. I 15 don't know. I don't remember that. 16 Q. But here the regulatory people at the CSM, the 17 British equivalent to the FDA, were finding that or believed 18 that if you reduced the dosage you would reduce the number of 19 reported adverse events; correct? 20 A. They say that that may -- that may decrease the 21 dose -- I'm sorry. That may decrease the frequency of the 22 adverse events by decreasing the dose? 23 Q. To 10 milligrams? 24 A. To 10 milligrams. 25 Q. D says Committee on Safety of Medicines members 88 1 appears to have a position that 10-milligram dose would be 2 effective; correct? 3 A. Yes. 4 Q. Would that be based on the 5-milligram data that 5 had been submitted to them? 6 A. I could only speculate about what they based 7 that on, but that's the dominant -- that's the only real good 8 efficacy data that's available. 9 Q. Because there never was any studies undertaken 10 to examine 10 milligrams, was there? 11 A. I don't believe there were studies at 10 12 milligrams. 13 MR. SMITH: That concludes the deposition of 14 Doctor Robert Zerbe, Your Honor. 15 JUDGE POTTER: Would each of you collect up 177, 16 71 and 87 and pass them over to the end and my -- 177, 71 and 17 87 you've got copies of. 18 MR. SMITH: I think she's already got them. 19 JUDGE POTTER: Ladies and gentlemen, we're going 20 to take the recess, and it will be 9:30 on Monday morning. As 21 I've mentioned to you-all before, do not permit anybody to 22 speak to or communicate with you on any topic connected with 23 this trial, and I emphasize that includes the news media that 24 might inadvertently try and speak to you about a topic by 25 having you watch them on television or read about them in the 89 1 newspaper. Do not discuss the case among yourselves and do 2 not form or express any opinions about it, and have a good 3 weekend, till 9:30 Monday morning. 4 (JURORS EXCUSED AT 11:55 A.M.; THE 5 FOLLOWING PROCEEDINGS OCCURRED IN CHAMBERS) 6 JUDGE POTTER: I guess you gentlemen just want 7 to know what their plans are? 8 MR. MYERS: Yes. As I understand it, the lineup 9 is Doctor Lord on Monday, to be followed by Doctor Browne 10 Monday or Tuesday, and then some depositions to be designated 11 to be read later in the week. 12 MS. ZETTLER: We'll get you Heiligenstein -- I 13 gave you the first part -- I've got like 40 pages left to read 14 on that, so I'll get you the rest of that this afternoon, and 15 Beasley probably sometime today. And we still haven't made a 16 decision on Wheadon, but if we decide to do it, we'll get it 17 to you real quick. 18 MR. MYERS: I'll work as rapidly as I can. My 19 only concern is Doctor Beasley and Heiligenstein are three 20 days or more. 21 JUDGE POTTER: Are you going home this weekend? 22 MR. MYERS: Yes, sir, but Ms. Zettler can fax 23 them today or tomorrow to Atlanta. But I will endeavor to get 24 those completed, but it's not like a one-day deposition. 25 MS. ZETTLER: We're really, really, really 90 1 cutting them down. 2 JUDGE POTTER: And they're readers and you'll 3 have at least two days, maybe three to get it done. 4 MR. MYERS: Judge, you asked this question last 5 week and we have not responded. We would like to file a reply 6 brief on the punitive damages question, and I was wondering if 7 we could make the filing right before the Breeders' Cup 8 holiday, if that's acceptable. 9 JUDGE POTTER: That's fine. 10 MR. MYERS: Thank you. 11 JUDGE POTTER: You-all will get an order in the 12 mail. We say some things here and sometimes I think it gets 13 lost in the clutter, so I'm sending out an order that I plan 14 to start thinking about instructions or doing a tentative 15 draft of my own in two weeks or something like that, and I 16 just gave you-all a date to which if anybody wants something 17 in front of me when I really start thinking about it... And 18 on a topic like this, 80 percent of it is probably in my head 19 from prior cases and 99 percent is probably in your-all's head 20 from prior cases, but you-all may want me to read something or 21 cases before I start thinking of it. It's two weeks away. It 22 may even be longer, I can't even remember. Anything else? 23 MR. STOPHER: No. Thank you. 24 (PROCEEDINGS TERMINATED THIS DAY AT 12:00 P.M.) 25 * * * 91 1 STATE OF KENTUCKY )( )( Sct. 2 COUNTY OF JEFFERSON )( 3 I, JULIA K. McBRIDE, Notary Public, State of 4 Kentucky at Large, hereby certify that the foregoing 5 Transcript of the Proceedings was taken at the time and place 6 stated in the caption; that the appearances were as set forth 7 in the caption; that prior to giving testimony the witnesses 8 were first duly sworn; that said testimony was taken down by 9 me in stenographic notes and thereafter reduced under my 10 supervision to the foregoing typewritten pages and that said 11 typewritten transcript is a true, accurate and complete record 12 of my stenographic notes so taken. 13 I further certify that I am not related by blood 14 or marriage to any of the parties hereto and that I have no 15 interest in the outcome of captioned case. 16 My commission as Notary Public expires December 17 21, 1996. 18 Given under my hand this the__________day of 19 ______________________, 1994, at Louisville, Kentucky. 20 21 22 23 24 _____________________________ 25 NOTARY PUBLIC 92 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25