1813 1 IN THE UNITED STATES DISTRICT COURT 2 FOR THE DISTRICT OF HAWAII 3 4 SUSAN K. FORSYTH, ) Civil No. 95-00185ACK Individually and as ) 5 Personal Representative ) Pages 1,813 - 2,024 of the Estates of June M. ) 6 Forsyth and William D. ) Forsyth, and WILLIAM F. ) 7 FORSYTH, JR., ) ) 8 Plaintiffs, ) ) 9 vs. ) ) 10 ELI LILLY AND COMPANY, ) an Indiana corporation, ) 11 et al., ) ) 12 Defendants. ) __________________________) 13 14 TRANSCRIPT OF PROCEEDINGS 15 The above-entitled matter came on for trial on Friday, 16 March 19, 1999 at 9:15 a.m. at Honolulu, Hawaii. 17 BEFORE: THE HONORABLE ALAN C. KAY 18 United States District Judge District of Hawaii 19 20 REPORTED BY: TINA M. STUHR, RPR, CSR #360 Notary Public, State of Hawaii 21 PACIFIC REPORTING SERVICES UNLIMITED, INC. 22 733 Bishop Street Suite 2090, Makai Tower 23 Honolulu, Hawaii 96813 (808) 524-PRSU 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1814 1 APPEARANCES: 2 For Plaintiffs: ANDY VICKERY, ESQ. Vickery & Waldner 3 2929 Allen Parkway Suite 2410 4 Houston, Texas 77019 5 KAREN BARTH, ESQ. Baum, Hedlund, Aristei, Guilford 6 & Downey 12100 Wilshire Boulevard 7 Suite 950 Los Angeles, California 90025 8 ROY K.S. CHANG, ESQ. 9 Shim & Chang 333 Queen Street 10 Suite 900 Honolulu, Hawaii 96813 11 For Defendant: ANDREW SEE, ESQ. 12 MICHELLE R. MANGRUM, ESQ. Shook, Hardy & Bacon L.L.P. 13 One Kansas City Place 1200 Main Street 14 Kansas City, Missouri 64105 15 EDMUND BURKE, ESQ. Burke Sakai McPheeters Bordner 16 Iwanaga & Estes 737 Bishop Street 17 Suite 3100 - Mauka Tower Honolulu, Hawaii 96813 18 Also Present: Catherine Itai 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1815 1 I N D E X 2 WITNESS ON BEHALF OF DEFENDANT 3 GARY DENNIS TOLLEFSON, M.D. PAGE 4 Cross-Examination (Cont'd) by Mr. Vickery 1816 Redirect Examination by Mr. See 1968 5 Recross-Examination by Mr. Vickery 1988 6 KENNETH TARDIFF, M.D., Ph.D. 7 Direct Examination by Mr. See 1997 Cross-Examination by Mr. Vickery 2011 8 Redirect Examination by Mr. See 2022 9 10 11 EXHIBITS ADMITTED INTO EVIDENCE: PAGE 12 Defendant's Exhibit 1049 - Letter 1987 dated June 3, 1992, from Carl C. Peck 13 to Ida Hallendar and Sidney M. Wolfe 14 15 16 17 18 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1816 1 (Whereupon, the following proceedings were had 2 in open court in the presence of the jury.) 3 THE CLERK: Civil No. 95-00185ACK, Susan K. 4 Forsyth, et al. versus Eli Lilly and Company, et al. 5 MR. VICKERY: Good morning, Your Honor. Andy 6 Vickery, Roy Chang, and Karen Barth for Bill and Susan 7 Forsyth. 8 THE COURT: Good morning. 9 MR. SEE: Good morning, Your Honor. Andy See, 10 Michelle Mangrum, and Ed Burke for Eli Lilly and 11 Company. 12 THE COURT: Good morning. Good morning, ladies 13 and gentlemen of the jury. Please proceed. 14 MR. VICKERY: Thank you, Your Honor. 15 CROSS-EXAMINATION (Continued) 16 BY MR. VICKERY: 17 Q. Good morning, Dr. Tollefson. 18 A. Good morning, sir. 19 Q. Yesterday, as we ended, we were talking about 20 the FDA and the European experience, and we're going 21 to get to that shortly. Before we do, though, I want 22 to ask you whether, from the time you joined Eli Lilly 23 in June of 1991 to the present, you have ever urged 24 your company to give a warning about the possible 25 relationship between Prozac and akathisia or PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1817 1 akathisia-induced suicide or violence? Have you ever 2 urged the company to do that? 3 A. I have not. 4 Q. Okay, sir. Now, we saw yesterday that in your 5 1991 article, right before you joined Lilly, you wrote 6 that, "In a very small minority of patients, 7 suicidality may on occasion be a true drug-induced 8 event." We saw that, right? 9 A. I think I had mentioned there was a possibility 10 based on case reports in the literature of that 11 association. 12 Q. Right. But it wasn't proven yet? 13 A. Pardon me? 14 Q. But what you said was, in all fairness, it 15 wasn't proven yet? 16 A. That is correct. 17 Q. Now, in 1992, you published another article on 18 this subject and you, again, talked about the numerous 19 case reports and peer-reviewed literature where this 20 possibility had been discussed, didn't you? 21 A. Could you tell me which article you're 22 referring to? 23 Q. Sure. Do you recall publishing an article 24 called, "Absence of a relationship between adverse 25 events and suicidality during pharmacotherapy for PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1818 1 depression"? 2 A. Yes, I do. 3 Q. And in that article -- I mean, the whole 4 purpose of that article that was authored by you and 5 other Lilly employees was to say, no. No. This isn't 6 really happening. There's really no proof of this. 7 Isn't that true? 8 A. Not precisely. I think when you do a 9 scientific study you attempt to address the question. 10 In the paper that you're citing, the question was, is 11 there temporally or in the same context of time an 12 association between a particular adverse event that a 13 patient might have on a drug and a change in 14 suicidality. At no premise, it was an exploration. 15 The data very conclusively showed the absence of that 16 relationship relative to the other study groups. 17 Q. Okay. I understand that. I'm with you. Let's 18 look at your article, if we may. The first page. 19 MR. VICKERY: May I approach the witness, Your 20 Honor? 21 THE COURT: You may. 22 Q (By Mr. Vickery) I have a copy here for you. 23 A. Thank you. 24 Q. Now, I'll ask Ms. Barth to kind of highlight in 25 the margin, if you would, where it says, "Recently" PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1819 1 down to the bottom -- right there. That paragraph 2 right there, we're going to read. Show us the top, 3 the head with the list of the authors and title if you 4 would. I want to just ask you to identify for us, how 5 many of these authors on this paper work for Lilly. 6 Of course, Gary Tollefson did, right? 7 A. They all are. It's clearly displayed right 8 underneath the authors' names that this was from Eli 9 Lilly and Company. 10 Q. All right. Now, we're going to zoom in on this 11 paragraph that says, "Recently, on the basis of 12 anecdotal observations, it has been suggested that 13 antidepressants may induce or facilitate the emergence 14 or intensification of suicidality in a small number of 15 patients." What does it mean when you put 7 to 14 16 there? 17 A. Those were the limited number of case reports 18 existing in the literature at this time that were 19 relevant to that comment. 20 Q. Is eight case reports or eight studies in 21 peer-reviewed journals by different authors a limited 22 number, Dr. Tollefson? 23 A. Yes. 24 Q. Okay. We're going to look at these in just a 25 minute, okay, that's your footnotes or references. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1820 1 "It has been further suggested that certain adverse 2 events during antidepressant therapy, for example, 3 akathisia or dysphoric psychomotor activation" -- are 4 those the same thing? Is dysphoric psychomotor 5 activation the same thing as akathisia? 6 A. Not exactly. 7 Q. A similar phenomenon? 8 A. There's an overlap, I think, would be fair to 9 say. 10 Q. "May be associated with the emergence of 11 egodystonic suicidality." What's egodystonic? 12 A. I would say probably the sense of being 13 unpleasant within the individual, not feeling calm. 14 It would be an upsetting like feeling. 15 Q. And again, you give us references 15 to 18, 16 right? 17 A. That's correct. 18 Q. Now, let's look at your references. If you'll 19 turn on the last page, and we've highlighted them and 20 I would just like for you to -- let's don't take too 21 much time with it, but the first one is the Damluji 22 and Ferguson article we talked about yesterday, right? 23 A. That's correct. 24 Q. And what's the title of that article? 25 A. Let's see. "Paradoxical worsening of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1821 1 depressive symptomology caused by antidepressants." 2 Q. What does the title tell us? 3 A. It tells us that there were presumably patients 4 that were being treated with an antidepressant, in 5 this case, Imipramine, who experienced, during the 6 course of treatment, a worsening of their depressive 7 symptoms including suicidality. 8 Q. Is it paradoxical because that's not what you'd 9 expect to happen; you would expect them to get better 10 and they get worse? 11 A. Well, you would expect the majority of patients 12 to improve, but of course, no medication treats all 13 patients. 14 Q. Okay, sir. Your second reference was to the 15 Teicher and Cole article of "The emergence of intense 16 suicidal preoccupation during Prozac treatment," 17 right? 18 A. Right. This is the one that followed Damluji 19 and Ferguson with the Imipramine-induced patients who 20 then responded to Prozac. 21 Q. Now, your third reference was to Dr. Teicher's 22 and Cole's response to your letter criticizing your 23 second reference, right? 24 A. Yeah. In essence, it's a duplication of number 25 eight. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1822 1 Q. Was it really a duplication or is it them 2 responding to your criticism? 3 A. Regarding their original six cases. 4 Q. And that's the one we saw yesterday -- 5 A. That's correct. 6 Q. -- where they said they weren't willing to 7 stick their heads in the sand. Do you remember that? 8 A. That was their term. 9 Q. Your fourth one is called Dasgupta, "Additional 10 cases of suicidal ideation associated with Prozac." 11 Now, how many were there in that? 12 A. My recollection was just a single case, but 13 this is an example. This same individual a year later 14 retracted that case and felt it was an erroneous 15 report. 16 Q. Is that Dr. Hoover? 17 A. No, this is Dr. Dasgupta. 18 Q. And retracted it because the person had the 19 same phenomenon, this new suicide, when they took 20 another serotonin drug, right? 21 A. I don't recall which drug. I believe the 22 patient took another antidepressant, again, failing to 23 respond, and again, showing suicidality during the 24 course of treatment failing to respond. And her point 25 was, this was nothing related to fluoxetine and that PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1823 1 the original case report, that hypothesis that 2 fluoxetine or Prozac was causing this problem, 3 appeared to be incorrect. 4 Q. Well, you're familiar with Dr. Hoover doing 5 that where she retracted it a year later because the 6 same thing happened when she took another drug that 7 affects serotonin? You're familiar with that, aren't 8 you? 9 A. I'm familiar with this concept that if you're 10 not responding to treatment, suicidality may emerge in 11 the course of non-response. I'm not aware of any 12 patients reported here, sir, that were having a robust 13 clinical improvement who had this experience. 14 Q. Then there's the Masand article, "Suicidal 15 ideation related to Prozac treatment." How many 16 patients in that one? 17 A. I don't recall. 18 Q. Then the King, Riddle, and Chappell article, 19 "Emergence of self-destructive phenomenon in children 20 and adolescence during fluoxetine or Prozac 21 treatment." Do you recall that article? 22 A. I recall it. 23 Q. Then the Koizumi article, "Prozac and suicidal 24 ideation in child adolescent psychiatry." These are 25 all peer-reviewed journals, aren't they? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1824 1 A. These are case reports in peer-reviewed 2 journals. 3 Q. Okay. Then Downs, Ward, Farmer, "Preoccupation 4 with suicide in patients treated with Prozac" in the 5 American Journal of Psychiatry. Are you familiar with 6 that article? 7 A. Yes, sir. 8 Q. Then Lipinski and colleagues, "Prozac-induced 9 akathisia, clinical and theoretical implications." 10 You're familiar with that article? 11 A. Yes. 12 Q. And those authors said that we think that 13 Prozac may be causing akathisia, didn't they? 14 A. The important word was "may." 15 Q. I understand that. Believe me, I fully 16 understand that. Then we get the Wirshing and the 17 Van Putten -- now, incidentally, was Theodore Van 18 Putten really the world authority on akathisia before 19 his death? 20 A. I don't think there was a singular world 21 authority. He was well-written in that area. 22 Q. And are you familiar with his writings? 23 A. Yes. 24 Q. One of them is called "The Many Faces of 25 Akathisia," is it not? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1825 1 A. That's the title, I believe. 2 Q. And what Dr. Van Putten pointed out was that 3 this phenomenon, akathisia, has many different faces. 4 You just can't put it in a little bitty box, you have 5 to really be looking for it, didn't he? 6 A. I think what he was saying is that there is a 7 common aspect of that that defines what is this 8 akathisia to the doctor, just like there are terms for 9 depression, how it presents can be different, but 10 there's a common denominator for making the diagnosis. 11 Q. Then you cite Rothschild and Lock, "Re-exposure 12 to fluoxetine after serious suicide attempts by three 13 patients, the role of akathisia." What they reported 14 on, and we haven't really talked about it too much, 15 except Dr. Healy did, is there are three people who 16 had intense suicidal thoughts on Prozac. They took 17 them off, the thoughts went away. In the hospital, 18 they put them back on, the thoughts came back. They 19 took them back off, and the thoughts went away. 20 That's what they reported, isn't it? 21 A. They reported that during the course of their 22 illness, they received Prozac, didn't respond to 23 treatment, had a worsening of suicidal thinking, and 24 as I recall, eventually were treated with other agents 25 or they failed to report whether they were ever PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1826 1 successfully treated. 2 Q. Now, Dr. Tollefson, is that a challenge, 3 dechallenge, rechallenge, dechallenge? 4 A. Only in the sense that the patient was exposed 5 to a particular drug on two occasions, and on those 6 occasions where they were clinically depressed, also 7 had symptoms of suicidality. 8 Q. Okay, sir. Then there's the Hamilton and Opler 9 article, "Akathisia, Suicidality, and Prozac," in the 10 Journal of Clinical Psychiatry, and those authors, as 11 well, say, we think there's a relationship, didn't 12 they? 13 A. They had, again, a hypothesis, an observation. 14 Q. Okay, sir. Now, my question is this: That in 15 addition to that, yesterday, I don't know if you were 16 in the courtroom when we read Eli Lilly's responses to 17 certain things that we asked your company to admit. 18 A. I was not. 19 Q. You were not? Are you aware of those, that 20 there were a number of different doctors in telephone 21 conferences with Eli Lilly who said things like, "My 22 patients, 3 out of 50 are agitated, they're wired. 23 They're bopping each other. One got akathisia." Were 24 you aware of all of those doctors that said that to 25 Eli Lilly? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1827 1 A. I'm not aware of all of those doctors, but with 2 clinical depression, two out of three patients 3 experience agitation as part of the disease state, so 4 I think that that would not be surprising. 5 Q. With all of these people suggesting, 6 Dr. Tollefson, that it was a possibility, not that it 7 was proven beyond a doubt, but that it was a 8 possibility, why didn't you urge your company to warn? 9 A. Well, I think we talked about warnings 10 yesterday, and when we talk about labeling, a warning 11 suggests that there's reasonable evidence that there 12 is a relationship between a drug and a side effect. 13 It was our opinion that there was not reasonable 14 evidence. It was the opinion of the Food and Drug 15 Administration that there was not reasonable evidence. 16 The paper, that you were so kind to share with 17 me, was an example of how we diligently try to explore 18 this issue, and that is, during around '91 and '92, 19 there were these several case reports that you 20 mentioned. People were interested in this topic. One 21 of the things that we did to be responsible was to 22 conduct an analysis to see, not just whether or not 23 there were differences in the rates of suicide, but 24 actually, were there any associations between people 25 on the sugar pill or drug between suicidality and a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1828 1 particular adverse event, such as this cluster of 2 being activated. We found no such relationship 3 between suicide and the activation kind of events. So 4 we addressed this question in a randomized controlled 5 clinical trial format, which is the preferred way, as 6 we've talked about before, to test one of these 7 hypotheses generated by the case reports. 8 Interestingly, this data has been reviewed by a 9 variety of outside experts -- 10 Q. Excuse me. 11 A. -- and the FDA -- 12 Q. Excuse me, Dr. Tollefson. 13 A. -- and we don't see these case reports -- 14 MR. VICKERY: Excuse me, Your Honor. Would the 15 Court instruct this gentleman to please stop when I 16 ask him to? He's gone way beyond asking my question. 17 THE COURT: He's responding to your question, 18 so I'll allow him to finish his answer. 19 Q (By Mr. Vickery) Okay. Carry on. 20 A. I was trying to complete my sentence, thank 21 you. 22 Q. Are you through now? 23 A. I am. 24 Q. Okay. Under the federal regulations that 25 govern warnings, are you supposed to wait for proof of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1829 1 a causal connection or are you supposed to warn 2 whenever, in the scientific evidence, you know, 3 there's reasonable evidence to cause red flags to go 4 up? Which is it? 5 A. I think I just stated when there is reasonable 6 evidence of a cause and effect, that would be the 7 code's definition of what should be in the warning 8 section of a label. In the absence of reasonable 9 evidence, it would not appear on a warning. 10 Q. Does the federal regulations specifically say, 11 sir, don't wait for causal proof? Warn whenever there 12 is reasonable evidence. Don't wait. Does it say 13 that? 14 A. It does not require causal evidence, you are 15 correct. It does require reasonable evidence of the 16 association. 17 Q. How about if we just look at it instead of us 18 talking about it. 19 MR. VICKERY: May it please the Court, Your 20 Honor, pursuant to the earlier request by both 21 parties, we ask the Court to take judicial notice of 22 Section 21 of the Code of Federal Regulations and to 23 instruct the jury regarding the nature of these 24 federal regulations. 25 MR. SEE: May we approach the bench, Your PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1830 1 Honor? 2 THE COURT: Yes. 3 (Whereupon, the following proceedings were had 4 at side bar out of the hearing of the jury.) 5 MR. SEE: The objection was that the Section 21 6 is very long. It is huge. If Mr. Vickery wants to 7 draw a particular item in that to the witness' 8 attention, I have no objection to that. The whole 9 thing is huge. There's no way the jury will 10 understand what's in there. 11 MR. VICKERY: That's all I want to do. I want 12 to direct his attention to the provision. 13 THE COURT: Show us what you want to do. 14 MR. VICKERY: Okay. There, and then we may 15 want to talk about the point there. 16 MR. SEE: Again, my position would be that this 17 does not come in evidence because the jury is not in 18 the position to interpret what a law or regulation is, 19 but if he wants to ask the witness about what it says 20 and what he thinks it means and that sort of thing, I 21 think it's appropriate, but the exhibit itself, the 22 law ought not come in evidence. The jury can't 23 interpret it by themselves. 24 MR. VICKERY: I agree entirely. We're going to 25 put it on the screen and read it. We'll all read it PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1831 1 together, but they never get this document. 2 THE COURT: Did you prepare an instruction that 3 you want the Court to give? 4 MR. VICKERY: I don't think either side did, 5 Your Honor. 6 MR. SEE: That's not correct. I did. 7 MR. VICKERY: Did you? 8 MR. SEE: Yes. 9 THE COURT: The final jury instructions? I'm 10 not talking about that. 11 MR. SEE: I didn't prepare a preliminary one, 12 no. 13 MR. VICKERY: I think all we would want the 14 Court to tell them is these are regulations of the 15 Food and Drug Administration and they have the force 16 and effect of law, but that Hawaii law, non-federal 17 law, governs this case. 18 MR. SEE: I think the last part is for the 19 final instruction about Hawaii law. It is not talking 20 about Hawaii law here, but I think instructing the 21 jury that these are federal regulations that apply to 22 the FDA, I have no problem with that. 23 THE COURT: I'll say these are federal 24 regulations which are cited by the FDA and they have 25 the force and effect of law. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1832 1 MR. VICKERY: Very well. 2 MR. SEE: I don't have any problem with that. 3 (Whereupon, the following proceedings were had 4 in open court in the presence of the jury.) 5 THE COURT: The Court will instruct the jury 6 that Mr. Vickery will be asking Dr. Tollefson about 7 some federal regulations that apply to the FDA, and 8 the Court instructs the jury that these regulations do 9 have the force and effect of law. 10 Please proceed, Mr. Vickery. 11 MR. VICKERY: Thank you, Your Honor. 12 Q. This is from the Code of Federal Regulations 13 Section 201.57, Warnings. "Under this section 14 heading, the labeling shall describe serious adverse 15 reactions and potential safety hazards, limitations in 16 use imposed by them, and steps that should be taken if 17 they occur. The labeling shall be revised to include 18 a warning as soon as there is reasonable evidence of 19 an association of a serious hazard with a drug. A 20 causal relationship need not have been proved." 21 Did you understand when you went in 1991 to Eli 22 Lilly, sir, that that was the law? 23 A. Not at the time I went to the company. I was 24 not exposed to regulatory science and academic 25 medicine. I have become aware of it. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1833 1 Q. And since you became aware of it, in light of 2 all of the scientific articles that you cited in your 3 own published article we just looked at, is what 4 you're telling us that you, Lilly, have decided that 5 all of those scientific articles aren't reasonable 6 evidence? 7 A. What I think I said is that we're talking about 8 a series of case reports that were not felt, not only 9 by Lilly, but by the Food and Drug Administration, to 10 not represent reasonable evidence, and again, not in 11 isolation, but in looking at the multiple large-scale 12 trials conducted, not only by Lilly, but the academic 13 community that have tested those hypotheses and shown 14 no credible scientific relationship, so in the weight 15 of the evidence or the burden of proof says there has 16 not been reasonable evidence. That would be my 17 opinion. 18 Q. Well, we're going to talk about the FDA now. 19 Ms. Barth, thank you. 20 In January of 1990, your company became aware 21 that the next month's edition of the Journal of 22 Psychiatry would have the Teicher-Cole article, and 23 their initial response was to tell the salespeople, 24 don't bring it up; isn't that true, sir? 25 A. I would suspect if they had not seen the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1834 1 article, that he would not advise the sales force to 2 engage in discussions, which they aren't grounded in 3 understanding. 4 Q. Let me revise my question. The first reaction 5 that Lilly had to that article was to tell the sales 6 force, here's the article, but don't bring it up; 7 isn't that true, sir? 8 A. I would suspect -- not having been there, but I 9 would suspect what was told the sales force is that if 10 there is a question about the product or the illness, 11 that you -- our sales force, of course, are not 12 physicians. If you're not comfortable, you should 13 make sure it's a medical to medical communication and 14 ask that doctor to call Lilly and to talk with Lilly's 15 medical staff and keep it a doctor to doctor 16 discussion. That's what I would suspect. 17 Q. Let's look and see if your suspicion is good. 18 What we're going to do here, Dr. Tollefson, just so 19 you know, we're going to look chronologically at what 20 Lilly did in response to the Teicher article. 21 A. Okay. 22 Q. The first document is dated January 30, 1990 to 23 Dista Sales Representatives. What's Dista? 24 A. It was the sales division of Eli Lilly and 25 Company that was handling Prozac. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1835 1 MR. SEE: Mr. Vickery, could you give us the 2 number? 3 MR. VICKERY: Oh, yes. I'm sorry I will do 4 that on each case. This is Plaintiffs' Exhibit 15. 5 MR. SEE: Give us one second. 6 MR. VICKERY: Yes. 7 THE COURT: What number? 8 MR. VICKERY: Plaintiffs' 15, Your Honor. 9 Q. And it's regarding the emergence of intense 10 suicidal preoccupation during treatment. This is the 11 Teicher article, right? 12 A. Yes. 13 Q. And we see here on January 30, first words, 14 "Enclosed is an article." So we know the salespeople 15 get it, right? 16 A. I assume it would be a preprint. In other 17 words, the Teicher article did not appear until 18 February's issue of the American Journal, so this 19 predates the actual publication of a final copy, so 20 this would be a preprint. I don't know if I'd treat 21 that as final, but apparently, a preprint was sent 22 out. 23 Q. How do you guys get ahold of the preprints? 24 A. It may have been shared by the investigator. I 25 have no idea. It may have a been a draft of the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1836 1 final. Typically, with these kinds of papers, the 2 author would receive a copy of it and has a chance to 3 review it. They're called galley proofs. 4 Q. This is January 30th, and the article is coming 5 out in the February edition. It's got to be pretty 6 close to final by then, doesn't it? 7 A. Again, I don't know the draft. I have no 8 recollection of what draft would have gone out, but 9 yes, again, my only point was that it predated the 10 actual publication in the journal. 11 Q. Okay. And they point out that among the 12 authors is Jonathan Cole, an opinion leader in 13 psychopharmacology, right? 14 A. We agreed on that yesterday. 15 Q. Now, if I were talking about opinion leaders on 16 psychopharmacology, this fellow, Professor Herman, 17 that was hired back in Germany in 1985 to study this 18 issue and came up with 5.6, he also was an opinion 19 leader hired by Lilly; is that not true, sir? 20 A. All I know was he was a consultant hired by 21 Lilly. I have no idea to what degree he was or was 22 not an opinion leader, but he was a consultant. 23 Q. If I show you a document later today where 24 Lilly said he's an opinion leader, will you accept 25 that? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1837 1 A. I have no reason to disagree with that. 2 Q. Then they start in this memo to tell the sales 3 representatives all about the cases in the article. 4 Let's go to Page 2. "Because these issues are not 5 part of our current marketing plan, you should not 6 initiate discussions on these articles. However, when 7 asked to comment on the issues raised, you should, 8 one, attempt to determine the physician's level of 9 experience and his or her concern; two, based on the 10 summary provided in this letter and the Muijen 11 article" -- you know about Muijen, don't you? 12 A. Um-hum. 13 Q. Is that a yes, sir? 14 A. That's a yes. 15 Q. I'm sorry, this lady doesn't have a um-hum key, 16 that's why I asked you that, because she tries to keep 17 me straight here. 18 A. I appreciate you keeping me straight as well. 19 Q. This is another article like Fava and 20 Rosenbaum, where if you look at what the author said, 21 it looks like there's no problem, but if you look at 22 the data, it shows that there's a problem; isn't that 23 true, Dr. Tollefson? 24 A. I don't know how you define "a problem." I 25 actually think, if I recall in that article, they were PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1838 1 comparing two antidepressants and fluoxetine was 2 actually looking much better than the comparative 3 antidepressant when it came to suicidality, a much 4 lower risk. 5 Q. I agree with you. That's what the authors 6 said. What I'm saying is, if you looked at the data, 7 if a critical person with a critical eye looks at the 8 data, it comes out different, doesn't it? 9 A. I would assume the authors were critical and 10 the peer-review process that lead to its publication 11 involved external experts who are also critical. 12 Q. Okay. Anyway, then they were told, as you 13 said, "Refer medical correspondence in Indianapolis, 14 any questions regarding our experience with the issues 15 raised." So we'll all understand, the vast majority 16 of these Dista sales representatives were trained 17 pharmacists, weren't they? 18 A. I think so, at the time. 19 Q. And did you not believe that the trained 20 pharmacists, having been given the article, having 21 been given the two-page letter from Lilly explaining 22 the article, were competent to answer the doctors' 23 questions about it? 24 A. Well, if I had a serious medical problem, I 25 don't go to a trained pharmacist. I go to a doctor. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1839 1 So I think that's number one. So I would see this as 2 a very responsible action. And number two, these 3 people had just received this. They did not have time 4 to even begin to understand what they had. There 5 needed to be some period of reflection and 6 communication, but again, the point was they were 7 encouraged to talk with the physician around this 8 issue, responsibly gather information and direct the 9 physician to the medical department at Lilly for a 10 doctor-to-doctor discussion. 11 Q. Now, Dr. Tollefson, how can you say, sir, they 12 were encouraged to do this when they're told twice in 13 the same memo, do not initiate discussions about this? 14 Which is it, were they told not to talk about it or 15 were they encouraged to talk about it? 16 A. I think neither. I think you're perhaps 17 confusing what, at least my interpretation of this is, 18 which is they were not encouraged to bring up 19 something that they weren't equipped yet to understand 20 or to discuss, not being physicians, not having had 21 time to look at this. They were told that if the 22 doctor raises this as a concern, please encourage them 23 to have discussions with the physicians, the medical 24 staff at Lilly. 25 Q. What is your interpretation of this sentence? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1840 1 "Again, because these issues are not part of our 2 current marketing plan, discussions should not be 3 initiated by you." What's your interpretation of that 4 sentence? 5 A. When a company works on a marketing plan, they 6 would bring the sales representatives together and 7 they would train them on information. These sales 8 reps, because of just receiving this, had absolutely 9 no training in how to deal with the question. Now, 10 I'm sure that that training was subsequently shared, 11 but at this point in time, they were equipped 12 proactively to have a professional discussion on the 13 matter. 14 Q. Let me ask you about your statement that you're 15 sure that they were subsequently trained. Did you 16 have anything to do with formulating the training for 17 these people after you came to Eli Lilly in June of 18 1991? 19 A. In the sense of conducting a number of the 20 papers that we have published in the literature to 21 provide information to them, yes, I know that they 22 were provided information about what Lilly results 23 were in these analyses. 24 Q. Well, the reason I ask that, you may not know 25 this, but we all have heard the testimony of a lady PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1841 1 named Amy Lee who was one of your sales 2 representatives here, and in September of '92, she 3 went to Indianapolis for a month of training and 4 doesn't recall anybody saying hide nor hair to her 5 about this issue. Can you tell us why? 6 A. Well, I suspect by that time frame, September 7 of '92, this had been an issue that had already been 8 reviewed in great depth and detail by regulatory 9 agencies, including the FDA, and they indicated that 10 there was no scientific evidence of a cause and effect 11 relationship. So by that time, I think that the issue 12 had been adjudicated by regulatory agencies, by the 13 academic community. 14 Q. Okay. We'll visit about that. That's what 15 we're talking about here is the FDA. January 30th was 16 our first memo. I want to take you now to early 17 February. Tell me who offices on the 12th floor of 18 Eli Lilly's building in Indianapolis? 19 A. I assume you're referring to building 74, which 20 would be the senior management of the company. 21 Q. The chief executive officer of the company? 22 A. That would be one of them. 23 Q. That was Mr. Woods at the time, right? 24 A. Yes. 25 Q. And the other top executives of the company? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1842 1 A. That's correct. 2 Q. Do you office on the 12th floor? 3 A. I do not and I have never. Some day, maybe. 4 Q. In February, or actually between January 30th 5 and February 7th, in that short seven, eight-day 6 period, there were a lot of show-stopper meetings on 7 the 12th floor on this very issue, weren't there? 8 A. There were a lot of intense meetings. This was 9 a subject taken very seriously. 10 Q. We're going to look now at two memos or E-mails 11 from the top scientist, Dr. Leigh Thompson, okay. 12 The first is Plaintiffs' Exhibit 98. Would it 13 help you if you had a hard copy? 14 A. That would be fine, thank you. 15 MR. VICKERY: May I approach the witness? 16 THE COURT: You may. 17 Q (By Mr. Vickery) February 7, 1990 to Allan 18 Weinstein. Is he one of the top executives? 19 A. No. He was a person in the medical department, 20 vice president in Lilly research laboratories, but not 21 a senior executive. 22 Q. Okay. "I am concerned about reports I get, re: 23 U.K." -- that's the United Kingdom, right? 24 A. Yes. 25 Q. "...attitude towards Prozac safety. Leber PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1843 1 suggested a few minutes ago we using the CSM data -- 2 who's Leber? 3 A. I assume this refers to Dr. Paul Leber who's 4 head of the neuropsychopharmacology division at the 5 FDA. 6 Q. This is a very up-government official, Dr. Paul 7 Leber, right? 8 A. Intermediate. 9 Q. Okay. He's the one -- he's the one in sort of 10 a watchdog role over Lilly about Prozac, isn't he? 11 A. I don't know if I'd agree with your 12 terminology, in a watchdog role. He overviews the 13 neuropsychopharmacology division at FDA, which would 14 all companies that are marketing products in the area 15 of neuropharmacology. 16 Q. And is his division that he oversees 17 responsible for the federal regulations of Prozac? 18 A. Yes. 19 Q. Thank you. "So Leber suggested a few minutes 20 ago, we using the CSM database." What's the CSM 21 database? 22 A. I don't recall what CSM stands for, but I 23 believe that it is a surveillance type of database, 24 post-marketing surveillance data base in the U.K. 25 Q. This is the very database that Dr. Jick wrote PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1844 1 his paper about with 172,000 patients, isn't it? 2 A. That's correct. 3 Q. But Eli Lilly has never done any independent 4 epidemiological work with that database, have you? 5 A. We have certainly had conversations with 6 individuals around these databases. We haven't, in 7 all cases, replicated work that's already been done. 8 Q. "He suggested using the CSM database to compare 9 Prozac aggression and suicidal ideation with other 10 antidepressants in the U.K." That's precisely what 11 Dr. Jick did in 1995, isn't it? 12 A. Yes. 13 Q. He compared Prozac with Imipramine and eight 14 other antidepressants in the U.K.? 15 A. I think he did it in '92 as well. I believe he 16 had two publications. 17 Q. Right. It's the second one that's really the 18 172,000 patients, isn't it? 19 A. I thought it was larger because it involved a 20 comparison of more drugs. I think the first paper was 21 a comparison of Prozac with a second agent, so 22 comparable groups per drug, just more drugs in the '95 23 paper. 24 Q. Exactly. "Although, he is a fan of Prozac and 25 believes a lot of this is garbage, he's truly a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1845 1 political creature and will have to respond to the 2 pressures. I hope Patrick realizes that Lilly can go 3 down the tubes if we lose Prozac and just one event in 4 the U.K. can cost us that." 5 Do you know who Patrick is? 6 A. I'd speculate he's referring to a physician in 7 the medical department in the U.K, a gentleman named 8 Dr. Patrick Keohane. 9 Q. And Dr. Patrick Keohane was the top scientist 10 in the Lilly organization in the U.K., wasn't he? 11 A. Physician, not a top scientist. He was the 12 head physician in the medical department. 13 Q. Okay. "You know my prejudice about Patrick." 14 Did you know that Dr. Thompson was prejudiced about 15 the top doctor in the U.K.? 16 A. I did not know that, but knowing Dr. Thompson, 17 he was a very unusual individual. He was very, very 18 demanding and very precise and so he would often get 19 frustrated with people at times if they didn't meet 20 his very high perfectionistic standards, so he was a 21 very interesting person to work with. 22 Q. "But if I hear one more problem about not 23 covering safety in the U.K., Allan, I'm going to be 24 really up in arms, Leigh." That sounds like 25 Dr. Thompson, doesn't it? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1846 1 A. Yes. 2 Q. Let's look at what else he wrote on the same 3 day, February 7th. This will be Exhibit No. 97. Now, 4 this one is another Leigh Thompson memo, but there are 5 more people that are getting it, Dr. Weinstein, 6 Dr. Patrick Keohane that we just talked about. Who's 7 Max Talbott? 8 A. He was the head of Lilly's regulatory division. 9 Q. This is the guy that deals with the FDA, right? 10 A. Correct. 11 Q. And Bob Zerbe, who is he? 12 A. He was one of the vice presidents in Lilly 13 medical. 14 Q. Okay, sir. "Prozac safety reports. I wish to 15 re-emphasize the message from Bob Zerbe and Max 16 Talbott in this regard in terms of the resource needs 17 to stay absolutely on top of every Prozac adverse 18 event report. Anything that happens in the U.K. can 19 threaten this drug in the U.S. and worldwide. We are 20 now expending enormous efforts fending off attacks 21 because of, one, relationship to murder, and two, 22 inducing suicidal ideation. 23 "The appropriate level of response is indicated 24 by Dan Masica himself and Charles Beasley immediately 25 flying to Boston to talk to the authors of the paper PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1847 1 on suicidal ideation." 2 Now, Dan Masica is the gentleman who preceded 3 you in your job that you were hired to take, correct? 4 A. Correct. 5 Q. So he was Dr. Beasley's boss? 6 A. That's right. 7 Q. And he and Dr. Beasley, as soon as they got 8 this preprint, got on a plane from Indianapolis to 9 Boston and went to talk to Drs. Teicher and Cole, 10 didn't they? 11 A. I think they took it very seriously and 12 responsibly. 13 Q. Did they go to Boston to talk to Drs. Teicher 14 and Cole? 15 A. I would assume, yes. 16 Q. "We have numerous foes such as the Church of 17 Scientology. The FDA is very, very skitterish. I 18 have talked to Paul Leber twice in the last several 19 days. We must not allow one day to lapse on 20 follow-up. Flying to, investigating, everything about 21 Prozac. Bob Zerbe can correct me for a wild guess, 22 but I would think we have 20 full-time equivalents, at 23 least, working just on post-marketing safety and, 24 support and if necessary, we will stop everything else 25 going on to provide more." PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1848 1 They had 20 people working on this full time, 2 didn't they? 3 A. That's what he says. 4 Q. "Every significant event about Prozac has been 5 a show stopper with 12th floor meetings immediately 6 with Earl, Mel, et cetera." Who are Earl and Mel? 7 A. These are senior executives, the so-called 8 12th-floor people you referred to earlier. 9 Q. "There could not be a fumbling of even minor 10 proportions on this because political pressure and 11 perception and public news, not science, could cause 12 us to lose this one, Leigh." Does that, again, sound 13 like Dr. Thompson? 14 A. It does. 15 Q. Okay, sir. Now, that's February of 1990, and 16 in March of 1990, Dr. Charles Beasley drafts the 17 rechallenge protocol that you and I were talking about 18 yesterday, doesn't he? 19 A. That sounds right. 20 Q. Okay. We're going to come back and talk about 21 that a little later, but is it your testimony, sir, 22 that the decision not to do that rechallenge study was 23 something that the FDA and your company jointly agreed 24 on? 25 A. My recollection of the events were that the FDA PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1849 1 had raised serious question about that method as a way 2 to answer the question. We internally made the 3 decision that given the other options we had to 4 evaluate that were more sound scientifically, that 5 those were the preferred methods. 6 Again, as I mentioned earlier, subsequent to 7 all of this, the FDA had reviewed the totality of the 8 information and concluded that there was no evidence 9 of the association. 10 Q. Dr. Tollefson, have you previously testified, 11 sir, under oath that there was disagreement within the 12 company, that one of the top people within the company 13 said, wait a minute. We've promised the FDA to do 14 this. That the company is the one that decided not to 15 do the study and that you didn't even know if the FDA 16 was told. Have you previously testified to that under 17 oath? 18 A. I'm not aware of having used those words, no. 19 Q. Okay. Let's look at them. We're going to look 20 at your deposition. We're going to look at Page 278 21 of the deposition. This is on Page 45 of the 22 miniscript. This has about six or seven pages on each 23 page. 24 A. I have it. 25 Q. Okay. Have you got it? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1850 1 A. Yes. 2 Q. We're going to start on Page 278, Line 5. 3 MR. VICKERY: Are you with us, Mr. See? 4 MR. SEE: Yes. 5 Q (By Mr. Vickery) Okay. Mrs. Bart would you 6 play this for us, please? 7 We don't have sound. We'll come back and do 8 this. We have our technician with us. We'll come 9 back after the break and do this, Doctor. 10 Now, by July of 1990, the interest in this 11 issue of Prozac-induced suicide had gone beyond the 12 scientific community into the public community at 13 large, had it not? 14 A. Yes. 15 Q. And can you tell us, from your boning up on 16 what happened before you got there, how your company 17 responded? 18 A. Well, I believe around that time, first, the 19 company voluntarily added terminology to the 20 post-introductory report section of the label for 21 Prozac, which was the section we discussed yesterday 22 that does not speak to causality, but merely that 23 events were reported or observed during the course of 24 therapy with a drug. 25 Q. Incidentally, I'm glad you brought that up. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1851 1 The company actually makes changes, not on this issue, 2 but just changes to the Prozac label pretty 3 frequently, don't you? 4 A. I'm not sure how you define "frequently," but 5 it's not infrequent, at least, I guess, that we might 6 make a label change. That's fair. 7 Q. How I would define it is about just shy of 8 three times a year, 28 times in 10 years, so about 9 every 4 months, there's some change in the label; is 10 that true? 11 A. That sounds reasonable. 12 Q. And do you expect the physicians like Dr. Neal 13 and Dr. Roberts, who prescribed Prozac for 14 Mr. Forsyth, to go back and read all that little print 15 four times a year or three or four times a year? 16 A. If they're using the drug, I would like to 17 think they would, that they would want contemporary 18 information. 19 Q. Okay. Let's look at July. We're going to look 20 at July 1990. The exhibit number is 104. This is 21 again, Dr. Leigh Thompson writing. "Paul Leber called 22 yesterday" -- 23 MR. VICKERY: I'm sorry, Mr. See, are you with 24 me? 25 MR. SEE: Yes, thank you. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1852 1 Q (By Mr. Vickery) "Paul Leber called 2 yesterday. I contacted him at 6:15 this morning, an 3 half-hour conversation, very, very pleasant with Paul 4 and Tom Laughren." Now, first of all, if the 5 government -- if these guys are your watchdogs, and 6 that's my term, is it a little odd to you that they 7 would be taking telephone calls from the people 8 they're supposed to be regulating at 6:15 in the 9 morning? 10 A. Well, I believe that the FDA is in Washington, 11 D.C. and that's a different time zone, so I think you 12 need to add an hour, so they probably received the 13 call at about 7:15, before the start of their business 14 calendar day. 15 Q. Do you think 7:15 is a reasonable time for a 16 government official to be taking a call from somebody 17 he's supposed to be supervising or regulating? 18 A. I suspect that's the best time to reach that 19 official before he or she is engrossed in meetings all 20 day. 21 Q. Okay. "The call was about suicide. They said 22 this morning's Wall Street Journal article in their 23 mind was, quote, trivial, and the reporter had called 24 them. However, this issue is building and will not go 25 away. They feel some data are required and wanted a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1853 1 study or studies of the issue." And then they go on 2 to discuss the studies. 3 Were you aware that in the summer of 1990, the 4 FDA was saying, let's do some studies? 5 A. I think the FDA was saying they were looking 6 for data. 7 Q. Okay. We're going to look later -- 8 A. It says, "They feel some data is required." 9 Q. We'll look later, when we get our TV, at what 10 you said earlier about this. Let's go to the second 11 page. "I informed him of the suicide expert meeting 12 next Tuesday and told him we would furnish him with 13 detailed reports, et cetera. He was very pleased, but 14 he said, quote, I agree that the experts on suicide 15 can give for you good testimony on 20/20, Nightline, 16 and 60 Minutes, but what we really need are good 17 data." 18 Now, were you aware that Eli Lilly had hired a 19 bunch of experts on suicide to give testimony for TV 20 shows? 21 A. I'm aware that the company used experts in the 22 field to respond to questions in the media. 23 Q. Would you agree with me that that part sort of 24 sounds like a PR strategy rather than a scientific 25 response? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1854 1 A. That part would. 2 Q. Okay. "We then said that Temple had asked that 3 we not effect label changes on the suicide issue 4 without clearing them with the FDA first." Back in 5 July of 1990, they knew that the suicide issue might 6 result in changing the label, in other words, giving a 7 warning, didn't they? 8 A. I don't think that's what it says. 9 Q. Well, how do you read that, "not effect label 10 changes"? 11 A. Well, you said "warning." There are many 12 different types of label changes. I mentioned that 13 the company voluntarily changed the post-introductory 14 report section. I guess I read this, since you asked 15 me, as this was a very important issue and they wanted 16 to make sure there was communication between the 17 company and the Food and Drug Administration. 18 Q. Fair enough. I agree with you. 19 A. Sounds reasonable. 20 Q. I agree with you. Look down lower, "He asked 21 that we fax him nothing unless he has agreed to it 22 beforehand. He said that someone has found that 23 mailbox and it makes a second route of information, so 24 he said he was warning people, like us, not to use fax 25 unless we had specifically agreed with him to do so." PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1855 1 Do you find it strange that a public official 2 at the federal Food and Drug Administration was saying 3 to Lilly, don't fax me anything at the FDA, don't send 4 me anything here, unless you call me first so I can 5 stand by the fax machine? 6 A. What I interpret from this is that he was not 7 feeling that he had security in the exchange of 8 information and was wanting to make sure it got to him 9 in a secure manner. 10 Q. Dr. Tollefson, you're familiar with all the 11 exhibits in this case, aren't you? 12 A. Yes. 13 Q. And are you not familiar, sir, with the fact 14 that Eli Lilly considered this man, Paul Leber, as 15 your, quote, defender on this issue? 16 A. I've seen that term used by Dr. Thompson, but I 17 think you don't want to take it out of context. I'd 18 be happy to explain what I think he meant if you'd 19 like. 20 Q. Well, what we'll do is just look at his memo 21 and everyone can decide for themselves without you 22 explaining it. 23 A. All right. 24 Q. "Paul is taking the position, in talking with 25 outside folks today, that Lilly and the FDA and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1856 1 working together," probably a typo, probably meant to 2 say are, didn't you -- "are working together on the 3 suicide issue, and following closely the 4 post-marketing events, but that there are not 5 denominators and the best that can be done is to put 6 a, quote, cap on the number of events." 7 What on earth does that mean, to put a cap on 8 the number of events? 9 A. Sure. If you look at post-marketing 10 surveillance for a drug, initially you get a number of 11 reports and so you have a number X, and it's somewhat 12 like we were talking about yesterday. You don't know 13 how many patients necessarily are taking the drugs, so 14 you don't know how to interpret that number of X. 15 So in other words, if you had 10 reports and 16 there are only 20 people taking the medication, that 17 would be one thing. If you had 10 reports and you had 18 a million people taking the medication, that's another 19 thing. So he's saying we don't have that denominator 20 to look at the ratio. So the only thing he was 21 suggesting is, I suspect, if that number of reports 22 reaches a certain level, or he used the term cap, 23 beyond that point, we'd have to take it as a positive 24 signal. 25 Epidemiological studies are used to look for PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1857 1 signals in these post-marketing reports, is there a 2 possible signal, and so they are saying, I think, that 3 if the number of reports exceeds a certain threshold, 4 we should take that as a possible signal. 5 Q. Dr. Tollefson, when we talk about the number of 6 suicides, are you familiar with the fact, sir, that a 7 few months later, Dr. Leigh Thompson said, look, we've 8 got some big numbers on suicides, but if we put them 9 next to nausea and talk about how many people our drug 10 makes throw up, then the numbers won't look so bad? 11 Are you familiar with the fact that he did that? 12 A. I think he was referring, my recollection, to, 13 again, these post-marketing reports. And if you think 14 about it, if you are a doctor and you have a chance to 15 do a post-marketing report on nausea, you're probably 16 not so likely to do it because it's not a serious 17 potential side effect. If you saw something like 18 suicide, you're more likely to report it. I think 19 what he was suggesting, perhaps, was that those 20 numbers together make it look like they're comparable 21 and it doesn't really reflect the tendency of doctors 22 to only report more serious things, be less likely to 23 report something like nausea or headache. 24 Q. We'll look at that as soon as we finish this 25 memo. I want to go back up because we didn't finish PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1858 1 this paragraph. We were on the middle of the page. 2 "After he talked about not faxing things, he said, I 3 think we better start using the Washington office more 4 aggressively to transmit stuff as this linked to the 5 break-in into Paul's computer, et cetera. I also want 6 to re-energize our periodic discussions about opening 7 an office adjacent to the Park Long Building 8 specifically for the purpose of expediting 9 submissions, dialog, and meetings." 10 Now, the Park Long Building is where Paul Leber 11 and the other watchdogs at the FDA office, isn't it? 12 A. Yes, at that time. 13 Q. And did your company ever open up an office 14 right across the street so you could not worry about 15 faxes, you could just hand deliver stuff to them? 16 A. It wasn't across the street, but it was within 17 a few blocks. 18 Q. Okay. I think we're done with that one. Now 19 we're going to look at this nausea document. This is 20 Exhibit 113. Are you with me now, Doctor? 21 A. I have the document. 22 Q. Okay. This is to Robert Zerbe from Leigh 23 Thompson in October of that same year, a few months 24 later, and apparently there was going to be a 25 November 10 symposium on Prozac, right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1859 1 A. It appears that way, yeah. 2 Q. Now, in a symposium, there would be other 3 people outside of Lilly and outside of the FDA, would 4 there not? 5 A. I don't know what the symposium was. I have no 6 reason to think the FDA would be participating, but I 7 don't know anything about the symposium. 8 Q. Let's look on Page 2 of what he says. 9 "Then" -- you with me? 10 A. I'm trying to. Okay. 11 Q. "The question is, what to do with the, quote, 12 big numbers on suicidality. If the report numbers are 13 shown next to those for nausea, they seem small." 14 Isn't he suggesting, sir, that in the symposium, if we 15 just show how many people vomited on this drug, then 16 the numbers won't seem as large for suicide? 17 A. He's trying -- I mean, I'm speculating on what 18 he was saying or not saying. Again, as I mentioned, 19 physicians would be more likely to report a serious 20 event than a non-serious, so you would expect the 21 absolute numbers of something like suicide during the 22 course of treating depression to be more likely 23 reportable than other events. So he may have been 24 trying to put things in some proportion, but I would 25 just be speculating on what he was thinking. I don't PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1860 1 know. 2 Q. Let me ask you this: If the jury were to 3 conclude, from the context of all of Dr. Thompson's 4 memos, that this is what he was trying to do, he's 5 trying to make the suicide numbers look small by 6 putting them right next to nausea numbers, as the 7 president of the neurosciences division of Eli Lilly, 8 can you tell us how you feel about that, if that's 9 what he was really trying to do? 10 MR. SEE: I object to the question. There's no 11 foundation, and I also object to its form. It calls 12 for speculation. 13 THE COURT: Sustained. 14 Q (By Mr. Vickery) Okay. Let's go back. We 15 had made it up to July, I believe, of 1990. Let's go 16 back to August of 199 -- I'm sorry, July 19th. This 17 is Exhibit No. 16. 18 MR. SEE: I'm sorry, Exhibit 16? 19 MR. VICKERY: Yes, 16. Plaintiffs' 16. 20 Q. Ms. Barth tells me this is one day later than 21 the one we looked at before in July. When he talked 22 to Paul Leber at 6:15 in the morning, it was on July 23 the 18th, and this is July the 19th, okay. 24 July 19, once again, to the salespeople, Dista 25 sales representatives regarding suicide, depression, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1861 1 and antidepressant therapy." And here, again, they 2 say, "There's no causal relationship concerning the 3 emergence of suicidal ideation, but these issues 4 continue to appear in the lay media. Because these 5 issues are not part of our current marketing strategy, 6 you should not initiate discussion of them." They 7 tell them, basically, the same thing in that memo as 8 they did earlier. Can you tell us, sir, what was the 9 current marketing strategy in July of 1990? 10 A. Not verbatim, no. 11 Q. Can you tell us generally what it was? 12 A. I think it was -- typically, the marketing 13 strategy is to focus on the basic attributes of the 14 medication and to differentiate it in the physician's 15 mind from other products that he or she might choose. 16 I mean, that's typically what a marketing strategy 17 would be as an effort to differentiate your product 18 from that of your competitors. 19 Q. And would part of a marketing strategy be, if a 20 doctor raises a concern about suicide, says hey, I 21 just happened to read The Wall Street Journal and, 22 unlike Eli Lilly or Dr. Leber, I put a lot of faith in 23 The Wall Street Journal and I read about this issue, 24 would the marketing strategy be to say, don't worry 25 about that, Doctor, not a problem; in other words, to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1862 1 reassure him that there was no problem with Prozac 2 causing this for some people? 3 A. I don't think -- I think what it says here is 4 that there was no evidence of that association in 5 general. I think that it also, as I recall, and 6 correct me if I'm wrong, but it seemed to me that just 7 a couple weeks after this went out, Lilly voluntarily 8 sent a letter to every physician in the United States 9 detailing the existing data, the issues provided them 10 a very comprehensive overview directly from the 11 company to every doctor in the U.S. 12 Q. I will correct you on that since you invited me 13 to. About two weeks after this, they told the sales 14 force to reassure the doctors. If this issue comes 15 up, reassure them. And about three or four weeks 16 after that, they sent out a letter to every doctor in 17 the United States which we'll talk about, okay? 18 MR. SEE: Your Honor, I object to the testimony 19 by counsel and ask that it be stricken. 20 THE COURT: Sustained. It will be stricken. 21 Q (By Mr. Vickery) Okay. We just looked at 17, 22 and that's to the Dista sales representatives. 23 A. I believe it's 16. 24 Q. I'm sorry, that's 16. 17 is the one we're 25 going to get to next. It's August 3rd. This is the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1863 1 one two weeks later. August 3 -- 2 MR. VICKERY: I'm sorry, Mr. See, do you have 3 it? 4 MR. SEE: I do. Thank you. 5 Q (By Mr. Vickery) Let me give it to the 6 witness. "Update on Prozac in the media. Recently, 7 amid reports concerning the emergence of suicidal 8 ideation and behavior possibly associated with Prozac 9 therapy, you were sent a marketing letter and 10 background on suicide, depression, and antidepressant 11 therapy to assist you in understanding this subject. 12 In that communication, it was stated that no causal 13 relationship between suicidal ideation or behavior and 14 Prozac had been demonstrated. That conclusion was 15 based on analyses of our U.S. clinical trial database 16 and post-marketing data event reports." 17 Now, we're going to come back and talk about 18 that later, but that's the Charles Beasley 19 meta-analysis of 3,000 patients, isn't it? 20 A. The U.S. clinical trials database reference, 21 yes. 22 Q. 3,000 out of the 27,000 that we had on the big 23 blowup you guys used yesterday, right? 24 A. Those that were in the double-blind trials that 25 permitted the comparison with the sugar pill or with PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1864 1 other drugs. 2 Q. Okay. And then again, they talk about the 3 Teicher and Cole article, and they say, "This 4 information is not intended to replace our current 5 promotional strategy that is being provided to enable 6 you to respond to physicians when appropriate. You 7 should not initiate discussions on these issues or use 8 this letter in detail. However, if asked to comment 9 on these issues by health care professionals, you 10 should, number one, reassure the health care 11 professional that no causal relationship has been 12 established between suicidal ideation and Prozac 13 therapy." 14 Don't you think, Dr. Tollefson, given all of 15 those articles that we saw that you cited later, that 16 what you should have said was, tell them that it might 17 happen, that it's an open issue, that there are lots 18 of scientific articles that say Prozac causes 19 akathisia or Prozac causes violence and suicide, watch 20 out for this. It might happen. Now, it hasn't been 21 proved, but it might happen. Don't you think that 22 would have been a fairer, more appropriate thing to do 23 than to simply reassure them that there was no causal 24 relationship? 25 A. I think you may be misinterpreting number one. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1865 1 Number one does not indicate that it hasn't been 2 observed or it hasn't occurred, it only indicates that 3 there's no causality between the drug and the event. 4 It's not saying that the event and treatment with 5 Prozac hasn't been observed in these case reports at 6 that point in time that they hadn't been observed. It 7 just says there's no evidence, based on very 8 exhaustive analyses of data, that there was a causal 9 relationship. That's different. 10 Q. I understand that. I'm just saying that before 11 you try to reassure them, shouldn't you have maybe 12 given them a few words of caution? Shouldn't you have 13 told them, okay, what -- I mean, this is 1990, okay? 14 In eight months later, you published an article in 15 which you said, "A very small minority of patients, 16 suicidality may on occasion be a true drug-induced 17 event." Shouldn't they have told them that rather 18 than simply reassure them? Couldn't they have said 19 that and then reassured them? 20 A. Well, I think it was added to labeling, as we 21 mentioned. The physician letter to all the doctors 22 went out very shortly after this detailing in great 23 depth the issues, and I think for the sales rep, the 24 key issue was -- you know, if you're a sales rep in 25 this situation, you know, you're looking to the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1866 1 company to let you know whether or not there is 2 evidence that there is a problem with the product. 3 What I interpret this to have said is we have looked 4 and we see no evidence of the drug causing the 5 problem. It was a reassurance. 6 Q. But you agree with me, do you not, that that 7 predates, by eight months, your article, your 8 published article where you said, "It may rarely be a 9 true phenomenon for a small percentage of patients"? 10 A. I think, Mr. Vickery, you may have forgotten 11 our discussion on the length of time it takes for an 12 article to actually publish from when I had written 13 it. It was published in '92 and was probably 14 initially written in '91. 15 Q. Excuse me, Doctor, this was published in May of 16 1991. 17 A. I'm sorry, that's not what I understood you to 18 say. 19 Q. This was published in May of '91. 20 A. Again, I think it reflects, at that point in 21 time, from a medical perspective, we had not achieved 22 any premature closure. We said that it was a 23 hypothesis, as case reports are, that needed to be 24 explored, so rather than me writing it is impossible, 25 I wrote that it was a hypothesis. It may be a rim and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1867 1 then we subsequently explored it in a number of 2 studies that were published thereafter. 3 Q. Do you think that maybe you should have told 4 the salespeople to do -- as part of reassurance, is to 5 say, there hasn't been any proof, but we were working 6 on a study, a rechallenge study, which is a good way 7 to either prove it or disprove it? Wouldn't that have 8 been a reasonable thing to tell the doctors? 9 A. No, because we never concluded that a 10 rechallenge study was a good thing to do or the 11 preferred thing to do. 12 Q. Well, Dr. Jick and Dr. Beasley both chose that, 13 didn't they? 14 A. No, that's not correct. I don't know what 15 Dr. Jick ultimately chose and what reference, but 16 Dr. Beasley, as I thought we talked about yesterday, 17 had reviewed with our entire team, a variety of 18 options. The team reached the consensus that that was 19 not a reasonable way to answer the question. It was 20 subject, as we talked about yesterday, to many flaws, 21 many misinterpretations, and the value, it had paled 22 compared to these large epidemiological studies or 23 randomized trials that we went through yesterday that 24 had been published. 25 Q. Okay. It also tells them, finally -- you PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1868 1 probably have also seen reports in the media about 2 several product liability lawsuits filed against the 3 company, as you know -- 4 MR. SEE: Your Honor, I object on relevance and 5 Rule 403. 6 THE COURT: Sustained. 7 MR. SEE: Your Honor, may we approach the bench 8 on that, please? 9 THE COURT: Okay. 10 (Whereupon, the following proceedings were had 11 at side bar out of the hearing of the jury.) 12 MS. MANGRUM: Your Honor, the Court 13 specifically ruled on March 4th that that was to be 14 redacted and Mr. Vickery assured us that he would 15 redact that before ever bringing it to the jury's 16 attention. That's the purpose of our objections and 17 our in limine motions that we brought to the Court's 18 attention long ago and he was not to do that by the 19 Court's order and by his agreement with us after the 20 Court's order. 21 MR. SEE: We haven't been checking these 22 documents. We just assume that he's doing it. 23 MR. VICKERY: What we tried very carefully -- 24 at this time, I don't remember the Court saying to 25 redact anything and I don't remember, in response to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1869 1 her objections, saying on this exhibit, okay? We have 2 been very careful to go back and check the things that 3 were supposed to be redacted and other indications 4 even though that's a wide open door. We've been very 5 careful. If I have overlooked one, I'm sorry. 6 THE COURT: You better. 7 MR. VICKERY: Well, give whatever -- 8 THE COURT: You want a limiting instruction? 9 MR. SEE: There's almost no way to make it 10 better. 11 THE COURT: Okay. 12 MS. MANGRUM: We asked you specifically to give 13 those to us. You knew this was out. 14 MR. VICKERY: Judge, if I've overlooked one, 15 and I may have, but I don't think so. I've tried to 16 be very careful about it. You want me to comment 17 about it in front of the jury, apologize in front of 18 jury, I'll be glad to do so. 19 MR. SEE: No. No. Your Honor, here's what I 20 request. I request that you simply say, Mr. Vickery's 21 last statement just read is stricken and the jury is 22 to disregard it without otherwise characterizing it. 23 THE COURT: Okay. Don't let it happen again. 24 (Whereupon, the following proceedings were had 25 in open court in the presence of the jury.) PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1870 1 THE COURT: The jury is instructed that the 2 last sentence read by Mr. Vickery is stricken and you 3 are to disregard it. 4 Please proceed. 5 MR. VICKERY: Thank you, Your Honor. 6 Q. You mentioned the Dear Doctor letter, and this 7 is -- it is Plaintiffs' Exhibit 22. We'll just look 8 at the first page of it. 9 Now, this is dated August 31, 1990, and we're 10 not going to read it. It's a long letter. The jury 11 will have it to read for themselves. My question for 12 you, is the tenor of the letter, the bottom-line 13 message that one gets from reading this letter, don't 14 worry about it, doc, not a problem, we've looked at it 15 and there's no evidence that our drug is causing this? 16 A. I don't see that, but if you want to give me a 17 minute to reread this, I'll be happy to. 18 Q. Why don't we do it that way. That would be 19 fine. 20 A. You want me to read it? 21 Q. Just to yourself. 22 A. Okay. Fine. Okay. I'm sorry, what was the 23 question? 24 Q. The question is whether or not you believe that 25 the overall tenor of this letter is to say, not a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1871 1 problem, no evidence to prove it, don't worry about 2 it? 3 A. No, not at all. Quite the opposite. 4 Q. Okay. We'll let the jury decide for 5 themselves. 6 MR. SEE: Your Honor, again I object to the 7 statement by counsel, gratuitous statement, and ask 8 that it be stricken. 9 THE COURT: Sustained. It will be stricken. 10 Q (By Mr. Vickery) Dr. Tollefson, were you 11 writing the May 1991 article in August of 1990? 12 A. Within that -- give or take maybe three or four 13 months, that sounds reasonable. 14 Q. Now, at that time, you were not employed by Eli 15 Lilly, but you had been retained by them on a 16 consulting basis to assist them with this issue, 17 right? 18 A. At what time frame? 19 Q. After February of 1990. 20 A. Yeah, I'm not sure. I remember consulting with 21 the company early in '91 before, I joined them, on 22 this issue. I really don't recall if I did it in '90 23 or not. 24 Q. Okay. In any event, at about the same time 25 that the company was saying there's no evidence in the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1872 1 causal relationship, you were writing for a 2 peer-reviewed journal that another question to answer 3 is whether there's -- a potential or suicidal ideation 4 is secondary to another drug side effect such as an 5 unpleasant akathisia, and that in a small minority of 6 patients, suicidality may on occasion be a true 7 drug-induced event. In your mind, before you started 8 getting your paycheck from Lilly, it was an open 9 question, wasn't it, sir? 10 A. No. I think it related to before I had access 11 to the data that had been generated by Eli Lilly and 12 Company. I think, you know, perhaps it's my fault 13 that I didn't make myself clear. At this time these 14 case reports generated a question, so I referred to it 15 as possible, needs to be explored, should be explored. 16 Subsequently and consulting with Lilly and then 17 eventually joining the company, it was explored and it 18 was answered definitively. 19 Q. But in August of 1990, at least insofar as you 20 knew, it was not answered definitively? 21 A. I did not have access at that point to the 22 entirety of the Lilly database. 23 Q. Okay, sir. 24 A. Now, certainly reflecting, and I think that was 25 probably also mentioned in my article, there are PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1873 1 investigators who had suggested that was not the case. 2 There were case reports that suggested that maybe it 3 was. The question was relatively open at that point. 4 Q. Okay, sir. That's August. I think we're going 5 to go next to September. And this is Plaintiffs' 6 Exhibit 109. 7 MR. SEE: Just one second. 8 MR. VICKERY: Yes. 9 MR. SEE: Thank you. 10 Q (By Mr. Vickery) September 12th, 1990, and 11 this, again, is Dr. Leigh Thompson writing, okay? 12 "Urgent, Dr. Leber with Dr. Laughren on the speaker 13 phone, called at 11:40 a.m., and Dan Masica and John 14 Heiligenstein joined me on the speaker phone." Now, 15 Masica is the guy whose job you took, right? 16 A. Correct. 17 Q. And Heiligenstein is a fellow that worked for 18 him and then you, right? 19 A. That's correct. 20 Q. And Heiligenstein is one of the fellows we 21 looked at yesterday who, in this very same month, 22 along with Dr. Charles Beasley, told Dr. Leigh 23 Thompson, hey, boss, don't blame the underlying 24 disease because we ourselves have put "reasonably 25 related" on the reports. Remember that discussion PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1874 1 yesterday? 2 A. I don't think that's quite what they said, but 3 I remember the discussion. I'd be happy to repeat it. 4 Q. "Leber said he was having a meeting with Bob 5 Temple in a couple of days to bring him up to speed on 6 suicidality." Now, who's Bob Temple? 7 A. He would be Dr. Leber's superior in the FDA. 8 Q. "He wanted to have the odds ratio analyses by 9 individual studies. We had faxed him the study group 10 odds ratio August the 6th, and he said there was 11 disagreement about how much data we have to have to 12 feel secure." 13 Odds ratios are things like, how much more 14 likely is it that someone will commit suicide or 15 violence on Prozac than on something else, whether it 16 be a sugar pill or Imipramine or something else, 17 that's what an odds ratio is, isn't it? 18 A. That's reasonable. 19 Q. That's an epidemiological term, isn't it? 20 A. Yes. 21 Q. "I think this means he is being pushed by 22 Temple and from Peck's comments yesterday, at least 23 Peck is concerned" -- do you know who Peck is? 24 A. Yes. He was in charge of the FDA at that time, 25 I believe. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1875 1 Q. So this is Temple's boss? 2 A. Correct. 3 Q. "...to change the label. Dr. Leber said he 4 would want the completed report draft in approval 5 stage by next week. Actions: Dan Masica is carrying 6 the odds ratio to Max to fax stat" -- that means 7 immediately in medical jargon, right? 8 A. That's correct. 9 Q. "...to Paul. He gave us permission to use his 10 fax," and then it gives a number. That's relating 11 back to what he talked about before, don't fax me 12 unless you call me first, right? 13 A. Keeping the document secure, yes, I think so. 14 Q. Let me ask you about that for a minute. Why 15 should the public's documents be hidden from the 16 public? 17 A. I don't believe that the types of documents 18 you're talking about here are public documents. Some 19 of this product information is submitted to what's 20 called the corporate or company's IND, meaning 21 Investigational Drug Application. Those, to the best 22 of my knowledge, are not purview to the public domain 23 or freedom of information. Those are considered trade 24 secrets around the molecule, so they're not public 25 documents. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1876 1 Q. And the company can, by designating it to go in 2 the IND file, put this shroud of trade secret 3 protection over it? 4 A. That's up to the FDA to decide, you know, where 5 the appropriate filing is, but if it's relevant to the 6 IND for the drug, then yes, it's not part of the 7 public domain. 8 Q. All right. Now, of course, the molecule -- 9 since you mentioned that, let's talk about that for a 10 minute. This has nothing to do with the molecular 11 structure of fluoxetine hydrochloride, does it? 12 A. It has to do with the product. It doesn't have 13 to do with its molecular structure, you're correct. 14 Q. And you know, do you not, sir, that the whole 15 nature of a patent law is that when you get a patent, 16 you have to disclose the molecular structure, don't 17 you know that? 18 A. Depends on what kind of patent you're talking 19 about. But I would admit that I'm not a patent 20 attorney, so I probably am not an expert to comment on 21 that. I'll have to defer to you. 22 Q. No, don't defer to me. I'll have you defer to 23 Doug Warner out here. 24 "I am now concerned" -- if you'll go down some. 25 "I am now very concerned that Temple and others may PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1877 1 force a label change even before we get there on 25 2 September or next worst, have this a fate accompli 3 (phonetically) when we arrive." In other words, he 4 was saying, I'm afraid that the top guys at the FDA 5 are going to either force us to change the label 6 before we get there or we're going to get there to 7 make our pitch to them and it's an accomplished fact, 8 a fate accompli (phonetically), right? 9 A. I think he's trying to say without having 10 access to all of the data or without an opportunity to 11 have a dialog around this, yes. 12 Q. "That report must move swiftly through approval 13 and to Dr. Leber's hands. He is our defender." Now, 14 if Leigh Thompson didn't mean that Paul Leber was 15 their defender when he wrote, "He is our defender," 16 what on earth did he mean? 17 A. Well, as I mentioned earlier, Leigh is a very 18 brilliant and very colorful person and these are the 19 kinds of people that use terms in many different ways, 20 but by defender, having my own experience with 21 Dr. Leber, Dr. Leber was, essentially, not a political 22 creature in the FDA. He was one that was steeped in 23 science and his decisions always reflected, I think, 24 good scientific thinking. 25 He was truly one of this nation's leading PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1878 1 experts in epidemiology and design in looking at drug 2 events, so I suspect Dr. Thompson was saying that if 3 you had to have anybody looking at this data, the 4 person you would want is Dr. Leber because of his 5 objectivity and his scientific credibility. So the 6 defense is only Lilly would like to rely on the data 7 and the science. Dr. Leber is someone who will 8 objectively, not under political pressure, not under 9 the media, but look at the data objectively and render 10 an opinion, which I believe he did as did the entire 11 FDA. 12 Q. Did you just testify that Dr. Paul Leber was 13 not a political creature? 14 A. I said he was not sensitive to those issues to 15 the same degree where he might not look at science. 16 If you were to rank order, Dr. Leber was a scientist 17 and data driven above all other things in my 18 experience in working with them. 19 Q. Let's look back real quickly at Exhibit 98. 20 Dr. Leigh Thompson, who called the man up at 6:15 or 21 7:15 in the morning, said, "Although, he's a fan of 22 Prozac and believes a lot of this garbage, he's 23 clearly a political creature and will have to respond 24 to pressure." Was he a political creature or wasn't 25 he a political creature? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1879 1 A. He was employed by the government and he was 2 certainly subject to those kinds of political issues, 3 but again, if it came down to political issues or 4 science, from my experience with Dr. Leber, he was 5 first and foremost someone who would look at the data 6 and objectively evaluate the data, who worked in a 7 political environment. 8 Q. He's not a political employee anymore, is he? 9 A. He has left the FDA. 10 Q. And is consulting for SSRI manufacturers, isn't 11 he? 12 A. I'm not aware of who he consults with. He 13 certainly does not consult, at present, for Eli Lilly 14 and Company. 15 THE COURT: All right. Let's take a break now. 16 Please be back at ten to eleven. I want to meet with 17 counsel. 18 (Whereupon, the following proceedings were had 19 in open court out of the presence of the jury.) 20 THE COURT: First, the Court is going to deny 21 Lilly's motion for judgment as a matter of law. The 22 Court finds that there are sufficient -- or there is 23 sufficient evidence for a reasonable jury to rule in 24 favor of the Plaintiffs' claims. However, the Court 25 notes that Lilly has made some strong points and the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1880 1 Court, if it was the ultimate fact finder, might well 2 find some of them persuasive, but the jury is the 3 ultimate fact finder and the Court finds that Lilly's 4 grounds do not rise to the level of granting the 5 motion for judgment as a matter of law. 6 Now, the Court is only ruling on the grounds 7 that were argued by Mr. See in court. There were some 8 additional grounds raised in the motion that 9 Mr. Vickery did not have an opportunity to argue. 10 The Court is going to ask its clerk now to 11 distribute to you the proposed jury instructions. 12 These are just preliminary, they're not final, but 13 they do indicate how the Court is leaning and they 14 resolve some of the remaining points in Lilly's 15 motion. We will have a hearing on the jury 16 instructions next week, but I want to give you an 17 opportunity over the weekend to be reviewing these. 18 Now, as far as the trial schedule, I think 19 yesterday, Mr. See felt that he might close Tuesday 20 afternoon or Wednesday morning, and it may not be 21 going as rapidly as you anticipated. 22 MR. SEE: That would be correct, Your Honor, 23 but I still believe at close of business on Wednesday, 24 we certainly ought to be done. No longer than that. 25 We may be done by noon Wednesday still. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1881 1 THE COURT: Okay. My only point was going to 2 be if, by some chance, we do wrap up all the evidence 3 including plaintiffs' rebuttal by Wednesday, you still 4 face three or four days off, and it might be better to 5 wait and argue the following week rather than arguing 6 on Thursday and then having a three or four-day void. 7 MR. VICKERY: I agree wholeheartedly with the 8 Court on that, Your Honor. 9 MR. SEE: I believe that's probably true, Your 10 Honor. I probably ought to raise it just to make sure 11 that the issue is before the Court. I don't know what 12 so-called rebuttal evidence that the plaintiffs have 13 in mind, but we certainly may have some differences of 14 opinion about whether it's appropriate rebuttal and 15 whether it ought to come in, but I'm sure that will 16 come up at the time. 17 THE COURT: Well, I suspect there will be a 18 number of issues. Let's take a break and be back at 19 ten to eleven. 20 (Whereupon, a recess was taken from 10:40 a.m. 21 to 10:55 a.m.) 22 THE COURT: Please proceed, Mr. Vickery. 23 MR. VICKERY: Thank you, Your Honor. 24 Q. Dr. Tollefson, I want to try to wrap up here 25 real quickly on the FDA and move on to other things. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1882 1 In this period we've been looking at from February of 2 1990, I believe from January 30, when you got the 3 preprint off the Teicher and Cole article up through 4 September of 1990, there were two ways that 5 Dr. Beasley had looked at to address this issue. One 6 was to do the rechallenge protocol that he drafted, 7 another was to go back and do a retrospective 8 analysis, in other words, look back at the clinical 9 trial data that had been done in something called a 10 meta-analysis; is that true? 11 A. Maybe just for clarification, I think 12 Dr. Beasley's protocol that you referred to was 1991, 13 not 1990. 14 Q. Do you still have it with you? I believe it 15 was March of '90. 16 A. If you could just help clarify for me. 17 Q. Sure. I could be wrong. I stand corrected. 18 You're right. March 29, '91. 19 A. Thank you. 20 Q. In studying this issue and in responding both 21 to the scientific press and Teicher and Cole, the 22 public media like 20/20, Nightline, The Wall Street 23 Journal, things like that, the concerns of the FDA, 24 did your company establish some priorities? 25 A. That's the question? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1883 1 Q. Yes, sir. 2 A. Yes. And obviously, this was the number one 3 priority to address, the scientific issues around 4 this. 5 Q. Well, so you say the number one priority was to 6 address the scientific issues? 7 A. Yes. I think that was reflected in 8 Dr. Thompson's message that you showed us, the number 9 of people. There was, essentially, no limit on the 10 number of people necessary to address the question. 11 It was a number one corporate priority. 12 Q. And was there also, in the prioritization, was 13 one of the priorities to protect patients? 14 A. That's always there. It is not unique to this 15 situation. 16 Q. Was one of the priorities to inform physicians? 17 A. Of? 18 Q. Of any potential problem here. 19 A. If we ever had reason to believe that there was 20 a direct problem related to Prozac, then the answer 21 would be yes. 22 Q. And was one of the priorities to protect 23 Prozac, this drug that we've seen that had caused 24 show-stopper meetings on the 12th floor and could 25 cause the whole company to go down the tubes? Was PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1884 1 that one of the priorities? 2 A. I guess I would ask you to define for me 3 protect Prozac, what you mean by that. It may not be 4 the same way that I would define protect. 5 Q. Rather than me do that, why don't we just look 6 at what Dr. Leigh Thompson, the top scientist at 7 Lilly, thought. 8 A. Okay. 9 Q. The exhibit is Plaintiffs' Exhibit 116. This 10 is a November 7, 1990 meeting. It's the final one in 11 our 1990 FDA sequence, and it's a memo, I'm sorry, 12 from Leigh Thompson, and it is to various guys. Who 13 are these first guys, Greg Inos and Charles Sampson, 14 do you know? 15 A. I know. I'm just trying to -- this is actually 16 multiple, multiple messages, so I'm just trying to put 17 it in the right perspective. Anyway, those two are 18 individuals that are senior statisticians in the 19 medical division. 20 Q. Is Dr. Bruce Dornseif also a statistician? 21 A. Yes. 22 Q. These are the guys that crunch the numbers? 23 A. Yes. 24 Q. And then there's Dr. John Heiligenstein. Is he 25 a psychiatrist? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1885 1 A. Dr. Heiligenstein is. 2 Q. Apologize to him for me when you get back to 3 Indianapolis. I didn't mean to mispronounce his name. 4 Now, November 5th down here, you're right, it 5 is multiple messages. It says, "In preparation for 6 PSC, various groups of us have been talking about our 7 ability to manage antidepressant clinical trials 8 worldwide. We need to be able to study five 9 antidepressants that are new, including," and there's 10 something that is not there because it is your private 11 information, right? 12 A. I'm assuming it is referring to a potential 13 product to be developed, yes. 14 Q. Right. And we understand that that's none of 15 our business, okay. "And probably do the FDA mandated 16 study with fluoxetine looking at suicidality." What 17 study had the FDA mandated to be done? 18 A. They did not mandate a particular study. I 19 think, in the message you showed us earlier back in 20 1990, the FDA was looking for data and had raised the 21 question of studying this issue, which, of course, we 22 did. I don't believe, or at least I'm not aware of a 23 specific study that was ever mandated to the company. 24 Q. Okay. Let's look at Page 2 about the 25 priorities. "This will require a very, very large PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1886 1 number of psychiatrists and patients in every country 2 possible. Assuming we all agree on that, then the 3 question is how to organize them. Should they all 4 work on one protocol design? Should they all work on 5 a single compound until it is, quote, done and then 6 roll over it to a second?" Are you schooled in 7 epidemiology, sir? 8 A. How do you mean "schooled"? Did I take 9 extensive academic classes in epidemiology or would I 10 refer to myself as an epidemiologist? No, I would 11 not. 12 Q. Are you generally familiar? 13 A. Generally, yes. 14 Q. I mean, all of those studies that Mr. See 15 handed you saying, does this support your opinion, 16 does this, you call those epidemiological studies, 17 don't you? 18 A. Yes. 19 Q. Now, when you were talking about or when 20 Dr. Thompson was talking about it back here, he said 21 it would require a very, very large number of 22 psychiatrists and patients. Can you tell us, sir, 23 why, if the phenomenon you're looking for is a rare 24 phenomenon, in other words, it doesn't happen to the 25 majority of people, it only happens to a few, as you PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1887 1 said in 1991, to a small minority of patients. If 2 that's the phenomenon you're looking at, does it 3 require a large number of patients in order to know 4 whether or not the drug is causing that phenomenon? 5 A. I guess two things. I think you mentioned 6 here, Dr. Thompson is referring to the concurrent 7 study of five antidepressants, so if you're studying 8 five at the same time instead of one, it's going to 9 take five times as many people or investigators, so I 10 think that's presumably where a very, very large 11 number comes from is to study five agents in parallel. 12 Q. Okay. 13 A. That would be a profound task. 14 Q. Okay. My question is, if what we're looking 15 for is a phenomenon that doesn't happen to the 16 majority of people, that only happens to, as you 17 wrote, a small minority of patients, isn't it true, 18 using standard epidemiological principles, you have to 19 look at lots of people, like the Jick study with 20 172,000 people, you can't just look at 654 and decide, 21 could you? 22 A. I don't think small versus large is the 23 ultimate answer. As we said yesterday, the preferred 24 approach to answering the question were randomized 25 controlled clinical trials. There you have to look at PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1888 1 statistical calculations, we call them power 2 calculations, to determine how many people you would 3 need to look at to answer the question within 4 reasonable confidence interval, and so, you know, that 5 will really dictate the size, but just bigger does not 6 equate with being better. 7 Q. I understand that. But you do have to have 8 enough people, if you're talking epidemiology, you 9 have to have enough people in the study to give it 10 enough power, as you say, for it to have some 11 validity, particularly if you're looking for a 12 phenomenon that only affects a few, true or not? 13 A. Yes, with the appropriate comparisons and 14 controls. 15 Q. And, of course, you know why I said 654, don't 16 you? 17 A. Maybe you could refresh my memory. 18 Q. That's how many patients that are in one of 19 those studies that Mr. See showed you yesterday, 654. 20 That's not enough to tell -- 21 A. Which study were you referring to? 22 Q. I forget which one it was. I'll point it out 23 to you. 24 A. I think that may have been one of the 25 follow-up's to NMIH collaborative depression study, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1889 1 which I think our field holds as the best long-term 2 depression study ever conducted. 3 Q. Okay. "What are our priorities? I suggest 4 that our priorities are, number one, protect Prozac; 5 number two, get" something, some other drug, 6 "registered for depression; number three, get any 7 other compound registered for depression; and number 8 four, get" blank "or others registered for any 9 non-depression indication." 10 What do you think about Dr. Thompson's priority 11 number one being to protect Prozac instead of to do 12 some true science, to inform some physicians, to 13 protect some patients? 14 A. I think that's included in what he said. 15 Knowing Dr. Thompson and his devotion to science, when 16 he says, "protect Prozac," he means let's get to the 17 bottom of this issue with the scientific data. And 18 I'm sure if Dr. Thompson had concluded that the 19 scientific data said that there was an issue, he would 20 have been the first to have advocated that 21 communication. But Dr. Thompson, again, is talking 22 about careful, well-conducted science and to 23 protect -- when he says, "protect," I assume what he 24 is saying is protect it against an image that might 25 not be based on science, rather something that was PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1890 1 enuendo, coincidental, but not factual. 2 Q. So protect Prozac really, in Leigh Thompson's 3 speech means to do some good science; is that what 4 you're telling us? 5 A. I think that would be one of the things that he 6 would certainly adhere to in thinking about this. You 7 have to recognize, in the position that he occupied, 8 this is a very -- it was and still is a very important 9 molecule, so that would be expected that he would say 10 that. 11 Q. What does down the tubes mean in Leigh 12 Thompson's speech? Remember the February 7th memo 13 where he said, "Our company could go down the tubes if 14 we lose Prozac"? Does that mean what we all think 15 down the tubes means? 16 A. Tell me what you think it means and I can let 17 you know. 18 Q. Right down the tube, right down the toilet, 19 flushed, gone. 20 A. I don't know if it would be flushed, but 21 obviously, I think he was reflecting this was a very 22 important product for our company. If there was a 23 major issue around it that wasn't part of scientific 24 fact, yeah, it was going to create significant 25 problems for the company. Pretty easy to understand. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1891 1 I think you're right. 2 Q. Okay. Next paragraph, "I suggest not only 3 using one protocol for several reasons, we have no 4 idea which design will work. We don't want to have a 5 hundred investigators in one protocol if it fails." 6 To hedge is best, isn't it? 7 A. I would need a moment to read that -- 8 Q. Sure. 9 A. -- if I may. I think he's saying here that at 10 that point in time he was not sure what type of study 11 or with which compounds would make the most sense, and 12 he was saying he did not want to -- if there were, 13 say, 150 capable investigators to do studies, he did 14 not want to tie up a hundred with something that he 15 was not 100 percent confident was the best way to go 16 forward. 17 Q. Let's read on down to the next paragraph. "Why 18 not try to, quote, count some of the patients on our 19 new compound in the 10,000 patients FDA wants us to 20 use in studying suicidality." 21 Now, I've got a couple of questions about that. 22 Why would Dr. Thompson put the word "count" in quotes? 23 Is he trying to kill two birds with one stone? 24 A. I think that Dr. Thompson was saying that 25 Lilly, you know, continues to develop new PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1892 1 antidepressant agents, so when he talks about new 2 compounds, I suspect he is reflecting on new possible 3 drugs, improved agents to treat depression in the 4 future, and if one were looking at the question, do 5 depressed patients get more suicidal and there were 6 additional new studies to be conducted against a new 7 compound, against the sugar pill, that kind of data in 8 studying depression should count towards this total 9 denominator of patients. It shouldn't be data that 10 would be excluded. 11 Q. Now, Dr. Tollefson, is there anything unclear 12 to you about the fact, from reading this memo, that 13 the FDA wanted Lilly to study 10,000 patients with 14 respect to suicidality? Is there any doubt in your 15 mind about that? 16 A. Yes. 17 Q. Yes. 18 A. Yes. 19 Q. Okay. What does the phrase "in the 10,000 20 patients FDA wants us to use in studying suicidality" 21 mean to you if it doesn't mean the FDA wants us to 22 study 10,000 patients with respect to suicidality? 23 A. Well, two things. I'm not aware of any 24 document or request to have done that, although it 25 precedes my being with the company, but I suspect, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1893 1 again, based on what I know at this time, there was a 2 lot of discussion about how to answer this question, 3 and this may well have been discussion in the context 4 of that ongoing dialogue about how to understand the 5 problem. That might be different than receiving a 6 formal letter that says you must study 10,000 patients 7 in a certain way. I suspect it was part of an ongoing 8 dialog. 9 Q. You think that he would just use 10,000 10 patients and say the FDA wants you to study 10,000 11 patients when he really didn't mean that? 12 A. I could speculate that, knowing Dr. Thompson, 13 that the FDA may have not said any number, but they 14 may have said it would take a large number of 15 patients, so that's why Dr. Thompson put 10,000 in 16 quotes. He was exaggerating a point. 17 Q. I see. And, of course, the meta-analysis done 18 by Dr. Beasley only studied 3,000 patients, true? 19 A. His did. My follow-up one had 10,500 patients 20 in it. 21 Q. We'll talk about that later, too. Now, down 22 here later in the last full paragraph he says, "This 23 way, we build a network of investigators. We tie them 24 up for several years. We get the maximum throughout 25 of antidepressant patients. We can count all the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1894 1 studies towards the FDA 10,000. We get the 2 comparative data on paroxetine" -- that's Paxil, 3 right? 4 A. That's correct. 5 Q. That's one of your competitors? 6 A. That's correct. 7 Q. Another SSRI drug? 8 A. Yes. 9 Q. "We get comparative data on paroxetine we 10 need," and you all needed that for the same reason you 11 said yesterday that they needed information on you, to 12 compete with one another, right? 13 A. Yes, he's referring to the new products. 14 Q. You wanted to show, we think we've got a better 15 mousetrap than SmithKline and Beecham who makes Paxil, 16 right? 17 A. Yes. 18 Q. "And we can try several different protocols; 19 complex, yes. Any simpler ideas? Leigh." Now, what 20 I want to ask you specifically about, Dr. Tollefson, 21 is his statement that, "we tie them up for several 22 years." Can you tell us what he meant by that? 23 A. Well, I can offer an opinion on that. 24 Particularly around this time frame, a lot of 25 companies were interested in doing depression studies, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1895 1 not only with existing drugs on the market where they 2 were doing these phase four studies that we talked 3 about, but also a number of companies were trying to 4 develop new antidepressants. And when it comes to 5 doing those studies, there are actually only a limited 6 number of investigators in the U.S. or, for that 7 matter, even worldwide, that really have the expertise 8 to conduct those trials, so one of the challenges is 9 you might be coming forth with this new medication 10 that you'd like to develop. You go to a center or 11 university and -- somebody might go to the University 12 of Hawaii, California, and talk to the investigator, 13 would you like to do this study for us, and the 14 investigator would have to stay, I can't. I'm already 15 doing three or four other studies. 16 So I think what he's talking about here is if 17 we had them involved with Lilly work, then we would 18 have access to working with them and we wouldn't be 19 faced with our competitors already having those sites, 20 the best sites tied up with other studies. 21 Q. So you don't think that he meant, let's tie 22 these guys up working for us so they won't publish 23 something that's contrary to us? 24 MR. SEE: Object to the form of the question, 25 argumentative. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1896 1 THE COURT: Sustained. 2 Q (By Mr. Vickery) Dr. Tollefson, are you aware 3 of a situation in which some fellows were going to 4 publish something about Prozac and suicide that you're 5 company didn't like, and your company sent a very top 6 executive all the way to Taiwan to visit with them, 7 they didn't publish, and then you hired those guys and 8 you put them under a several-year contract so that 9 they would be on your side? Are you familiar with 10 that situation? 11 A. I'm not sure your recollection of the situation 12 would be the same as mine, but I know the generalities 13 of what you're describing. 14 Q. This is Dr. Woo and Dr. Lieu, right? 15 A. No. 16 Q. Or I'm sorry, pronounce the names for me. 17 A. I'm not sure who you're talking about. 18 Q. You know the Taiwanese doctors that had the 19 maprotiline versus fluoxetine? 20 A. I think you may mean Dr. Liu and Dr. Ko. 21 Q. Liu and Ko? 22 A. Yes, and they are from Taiwan. 23 Q. And they had drafted a study about suicide, 24 right? 25 A. That's incorrect. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1897 1 Q. Well, what did they draft a study about? 2 A. They didn't draft a study at all. 3 Q. They didn't have a draft paper? 4 A. I'm sorry, I guess it reflects -- my apologies 5 because I think you're probably not aware of 6 scientific methods. They had study data that was 7 completed, so they didn't have a draft protocol or 8 proposals. They came in with some data that they had 9 written up into a paper. They came in specifically 10 asking our opinion about the data because they were 11 interested in publishing it in a top-tier American 12 psychiatric journal. 13 Q. Okay. Let's look at the memorandum that deals 14 with this. Forgive me, I skipped ahead of my 15 colleague here. Exhibit No. 144. We're looking at 16 Plaintiffs' Exhibit No. 144, Doctor. This is an 17 April 8, 1992 memorandum and it's from Allan 18 Weinstein. Who is he? 19 A. He is the senior medical physician at Lilly 20 responsible for our Asia Pacific region. 21 Q. How high up is Dr. Weinstein in your 22 organization? 23 A. Moderately high. 24 Q. All right. And we see that he's listed a whole 25 bunch of people here. Who's the top-ranking guy in PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1898 1 the list of folks that got this memo? 2 A. I believe Vaughn Bryson. 3 Q. Vaughn Bryson, and who is he? 4 A. Well, I'm not precise with my dates, but he 5 became the chief executive officer of Eli Lilly and 6 Company around that time frame. 7 Q. So the top guy in the company, right? 8 A. That's correct. 9 Q. Now, regarding Prozac in Taiwan. "Mission 10 successful. Professor Liu will not present or publish 11 his fluoxetine versus maprotiline suicidality data. 12 We will work with him in the very near future to 13 design a prospective randomized control double-blind 14 study of fluoxetine versus maprotiline." 15 Now, does "mission successful, he won't 16 publish" mean anything to you, sir, other than I've 17 succeeded in my mission and this guy is not going to 18 publish this data? 19 A. I think in order to answer that, one has to 20 look at what that data was and the deliberations that 21 we had with the investigators, and they agreed not to 22 publish it and there was a very specific reason for 23 that that I'd be happy to share with you. 24 Q. Well, were you involved in giving the mission 25 to Dr. Weinstein? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1899 1 A. I doubt it. I don't recall, but I would doubt 2 it. Dr. Weinstein did not report to me. 3 Q. Who in the company would have given him this 4 mission? 5 A. I believe that Dr. Weinstein reported to 6 Dr. Thompson, Leigh Thompson, so I suspect that may 7 have been the case. 8 Q. And is one of the ways that the mission was 9 accomplished by Eli Lilly agreeing to pay money to 10 these people to fund a study in the future which 11 would, quote, tie them up for several years? 12 A. No. I think you may be mistaken on this. 13 These were, as I mentioned to you, investigators who 14 were interested in publishing some data in a top-tier 15 American journal. We were under the impression when 16 they came in that they had conducted a prospective 17 comparison of these two drugs. In fact, when they 18 shared their data with us, they had not, and they had 19 done it, and I'm happy, if you'd like, to explain what 20 they had done, but their study was not a comparison of 21 the two drugs and it would never have been publishable 22 in a top U.S. journal. We told them that. 23 We suggested if they were really interested in 24 evaluating these two medications, that a randomized 25 prospective control double-blind study would be the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1900 1 way to get it published in that type of journal. We 2 were happy to work with them on it. We, in fact, 3 volunteered to fund the study if they would like to 4 conduct it in Taiwan. 5 Q. And, in fact, you did fund their study, didn't 6 you? 7 A. We offered the funding and they were interested 8 in doing the work and we provided the funding, as we 9 had committed, to try to address the question 10 properly. 11 Q. And what kind of level of funding are we 12 talking about? 13 A. I do not know. I would speculate for a study 14 of this size, it was -- typically, when you do a 15 depression study, the total cost to the investigator 16 and his site are on the order of 4 to $5,000 for the 17 entire study per patient, and so if this were a couple 18 of hundred patients, you know, it could approach a 19 million dollars. So it could have been in the several 20 hundred thousand dollars to a million-dollar range, I 21 would suspect. 22 Q. Dr. Tollefson, you yourself have filed a sworn 23 declaration in this case concerning Lilly's 24 relationship with these doctors, haven't you? 25 A. I don't recall it. I'd be happy to see it. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1901 1 Q. Let's look at it. Here we have it right here. 2 It says, "Declaration of Gary D. Tollefson, M.D., 3 Ph.D." That's you, isn't it? 4 A. It is. 5 Q. And you signed this declaration under pangs and 6 penalties of perjury in this very case, did you not, 7 sir? 8 A. May I have just a moment to look at it? 9 Q. Certainly. 10 A. Okay. Thank you. 11 Q. Did you -- it says, "I declare under penalty of 12 perjury that the foregoing is true and correct"? 13 A. I definitely signed it. I can't recall if this 14 is relevant to this case. I'll take your word for 15 that, but yes, I obviously have signed it. 16 Q. Ms. Barth, if you would zoom in a little bit. 17 I have a little fuzzy picture here. We'll follow 18 along on the TV set. Would you just read it? It's a 19 very short declaration. 20 A. You want me to read the entire document? 21 Q. Out loud, yes. 22 A. Sure. It starts out with my name, "Gary D. 23 Tollefson, M.D., Ph.D., of lawful age, states and 24 declares as follows: I'm a vice president of Lilly 25 Research Laboratories, Eli Lilly and Company, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1902 1 Indianapolis, Indiana. 2 In my position at Eli Lilly and Company, I have 3 access to information concerning Lilly-sponsored 4 fluoxetine clinical trials in the United States and 5 around the world. I recently reviewed the status of a 6 fluoxetine clinical trial Eli Lilly and Company is 7 currently sponsoring in Taiwan. The principal 8 investigators in that study are Dr. Reuben Lu and 9 Dr. Harold Ken Ko. The Taiwanese study referenced in 10 paragraph two of this declaration is a four-year 11 project entitled, quote, a multi-center, double-blind 12 and parallel study of fluoxetine and maprotiline in 13 patients with major depressive disorder, end of 14 quotes. 15 "The goal of this study is to enroll 400 16 patients by the end of 1998. As of October 23, 1997, 17 290 patients have already been enrolled. 18 "I declare under penalty of perjury that the 19 foregoing is true and correct, executed on February 3, 20 1998, and signed by myself." 21 Q. Now, these gentlemen, who did not publish 22 because a mission had been accomplished, were 23 subsequently engaged by Lilly to do a four-year study, 24 weren't they? 25 A. Not quite. I think that we had discussions PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1903 1 with the investigators the type of design that likely 2 would allow them to publish in a top-tier American 3 journal, which was their goal. Those types of studies 4 are done carefully. They want to do that in Taiwan. 5 There were not a lot of sites, so they needed to 6 collect more Taiwanese patients at their site and have 7 fewer sites. This was a standard time frame for that 8 to have been accomplished, but it was their desire to 9 conduct this. We merely provided them the funding so 10 that they could do the study. 11 Q. Is that study still ongoing? 12 A. I believe it is near completion, but I think it 13 is still ongoing. 14 Q. Okay, sir. And, of course, nobody could 15 publish the results of it until the study is 16 completed, could they? 17 A. That's correct. 18 Q. So in that sense, whatever knowledge, whatever 19 data these gentlemen had concerning Prozac and 20 suicidality back in 1992 has been tied up for all of 21 these years and is still tied up as we sit here today; 22 isn't that true, sir? 23 A. No, sir. 24 Q. Why not? 25 A. These gentlemen came in and, I guess, since you PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1904 1 keep bringing this up, I should provide the 2 appropriate background. 3 Q. Sure. 4 A. It was our understanding that they had 5 conducted a prospective study of Prozac with this 6 other antidepressant maprotiline. In other words, 7 prospective study meaning patients came into their 8 clinic and they were randomized. The patient didn't 9 know, the doctor didn't know to one drug or the 10 other -- 11 Q. Dr. Tollefson, excuse me just a minute for 12 interrupting you, but I need to ask you to pause right 13 there and give me a chance to confer with your 14 counsel. 15 A. All right. 16 (Whereupon, Mr. Vickery is conferring with 17 Mr. See.) 18 Q (By Mr. Vickery) I've conferred with Mr. See, 19 and we'll defer this explanation until after he has a 20 chance to confer with you over the lunch hour, okay? 21 A. All right. 22 Q. Does the FDA know everything about a drug when 23 it's first released? 24 A. I'm not sure how -- I'm not sure of your 25 question. The FDA would certainly be aware of all of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1905 1 the existing data at that point in time about the 2 drug. So at that point in time, yes. As time goes 3 on, they may learn additional things about the drug. 4 Q. Why don't we just -- you're familiar with their 5 MedWatch program, aren't you? 6 A. Yes. 7 Q. You've seen their one-page fliers that make 8 their position crystal clear, haven't you? 9 A. Yes. 10 Q. Let's look at it. This is Exhibit No. 26. 11 "When a drug goes to market, we know everything about 12 its safety. Wrong. 1-800-FDA-1088. FDA MedWatch." 13 They don't know everything about the safety at all, do 14 they? 15 A. My point was at the time the drug is marketed, 16 the FDA has available all the data that exists around 17 the product, so at that point in time, they know 18 everything that exists that is to be known about the 19 drug. Over time, there is more to be learned. This 20 is a very nice prompt to remind physicians to continue 21 to report things through the MedWatch system so there 22 can be a continuing learning experience. 23 Q. What they know, Dr. Tollefson, is what Eli 24 Lilly has submitted to them. They don't have the 25 resources to go out and do independent studies and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1906 1 independent research. They depend on the 2 manufacturer, such as Eli Lilly and Company, to 3 provide good, accurate information to them, don't 4 they? 5 MR. SEE: Object to the form of the question, 6 compound and argumentative. 7 THE COURT: Overruled. 8 THE WITNESS: Could I have you repeat it? 9 BY MR. VICKERY: 10 Q. Yes, sir. The FDA depends upon the company 11 like Eli Lilly to provide it with good, accurate 12 information, don't they? 13 A. Yes. Although, the FDA also will audit that 14 information at a clinical investigative site, go out 15 and look at the actual data that the physician has 16 generated to make sure that they're comfortable that 17 what's being reported by the investigator is 18 consistent with what the company is presenting. 19 Q. Has your company in the IND, NDA -- 20 investigative new device and the new drug application, 21 literally inundated the FDA with millions and millions 22 of pages of documents? 23 A. I don't know the exact number, but I think 24 we're very, you know, likely to have over, what is it 25 now, 11 years in the market and some 10 years before PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1907 1 market, so we're talking about 20 years of research, 2 it's very possible that it could have, over 20 some 3 years, achieved that kind of volume. 4 Q. And you're aware that they simply don't have 5 the manpower to look at all of that information? They 6 have to look at the summaries that you fellows 7 provide, don't they? 8 A. That's not been my experience. They have been 9 very diligent in looking at materials. If they have 10 questions, they're very quick to pick up the phone and 11 call us back and say, hey, I need more information 12 about this or can you clarify that. 13 Q. Bring it by the office, but don't use the fax 14 unless I tell you? 15 A. Well, I think when I saw your note that you 16 showed all of this, it referred to Paul's computer, 17 Dr. Leber, and it said his computer had been broken 18 into. So I guess, you know, if someone had broken 19 into my computer, I'd be a little bit nervous and 20 anxious at that point in time. 21 Q. Okay. From a scientific standpoint, whether 22 we're talking biostatistics, like Dr. Bruce Dornseif, 23 or whether we're talking epidemiology like Dr. Jick or 24 Dr. Jean Hoepfel, you're familiar with the concept, 25 garbage, in garbage out, aren't you? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1908 1 A. I've heard the term. 2 Q. And what does it mean to you? 3 A. I suppose that if somebody put in meaningless 4 data or data that had not been -- that the confounds 5 and things, that might complicate interpretation of 6 the data that had not been done, and we had not had 7 the proper figure up front, that then what you would 8 look up subsequently may be subject to those same 9 flaws. 10 Q. Now, tell us what we're going to see in a few 11 minutes, some acronyms, so let's go ahead and get what 12 they are right now. In fact, I'll write them so we 13 can bear them in mind. DEN, what's that? 14 A. Drug Epidemiology Network. 15 Q. Is this a network of computers within Eli Lilly 16 which has collected data over the years? 17 A. Spontaneous adverse events are entered into a 18 database, a computer system, and we refer to that 19 sometimes as the DEN database. 20 Q. Okay. Now, these are these spontaneous or 21 anecdotal reports, right? 22 A. That's correct. 23 Q. And so if someone, for example, calls 24 1-800-FDA-1088, and says, well -- whether that person 25 is a doctor or patient, and says, I took Prozac and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1909 1 suddenly within a few days began to have strange, 2 bizarre, violent thoughts of killing myself, that's 3 the kind of information that would be entered into the 4 Drug Epidemiology Network, correct? 5 A. Well, you said that they called the FDA. The 6 FDA maintains their own database, so if someone were 7 to call the FDA, it would enter first into the FDA's 8 database. Eventually, the FDA would likely notify us 9 of the case and it would then enter our database as 10 well, but there could be certainly a time difference 11 or lags in that. 12 Q. And if they reported it to Lilly, and we're 13 going to look at one in a little bit, a doctor that 14 reported one to Lilly first, then you put it in your 15 Drug Epidemiology Network into the computer, and then 16 report that to the FDA, right? 17 A. That's correct. 18 Q. On a form they call a form 1639? 19 A. Correct. 20 Q. Okay, sir. Now, when did the Drug Epidemiology 21 Network start at Lilly? 22 A. I don't know. 23 Q. Did it start before you got there? 24 A. I suspect, yeah. 25 Q. Are you aware of the fact that some of the data PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1910 1 that Lilly collected over the years preceded the Drug 2 Epidemiology Network on Prozac? 3 A. There was probably a different system that 4 predated that computer database. That makes sense. 5 Q. Okay. Now, another acronym we're going to be 6 seeing is called an ADE. Can you tell us what that 7 is? 8 A. I assume you mean adverse drug event. 9 Q. And what is an ADE or adverse drug event? What 10 do we mean by that? 11 A. Essentially, that could be any experience 12 reported during the time that an individual was taking 13 the medication, so it could be psychological, 14 physical, any experience. 15 Q. And it may or may not be related to the drug? 16 A. Absolutely. 17 Q. In fact, one of the things that you have 18 written in published literature and said, I believe, 19 in testimony is that typically, adverse drug events or 20 drug reactions happen soon after the drug starts, 21 right? 22 A. Well, you did use two different terms. An 23 adverse drug event and an adverse drug reaction, I 24 wouldn't say, are synonomous, so which one are we 25 talking about? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1911 1 Q. Well said. I'm talking about an adverse drug 2 reaction. I'm talking about an iatrogenic reaction, 3 iatrogenic reaction, a drug-induced reaction. That 4 happens shortly after the person starts taking the 5 drug usually, doesn't it? 6 A. I think, with any medication, you tend to see a 7 higher incidence of adverse drug reactions earlier in 8 the course of treatment for two reasons; either people 9 stop taking the medication because they don't like the 10 reaction, or they typically will accommodate to the 11 reaction and they no longer have it, so you do see 12 them earlier than later typically. 13 Q. Typically, within the first what, two to four 14 weeks, if it's drug related? 15 A. It would really depend on the individual drug, 16 but that's not an unreasonable approximation, but it's 17 very much dependent on the particular medication. 18 There's some that, you know, could be sooner or some 19 that could be later. 20 Q. So with Prozac, if someone had an adverse drug 21 reaction caused by the drug, generally speaking, would 22 you expect that to happen within the first month? 23 A. Yes. 24 Q. Okay. And if the person, say, was on the drug 25 for nine months, but you were concerned whether the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1912 1 reaction they had was caused by the drug, you would 2 really want to look at the first month, wouldn't you? 3 A. Not in exclusion, no. I think you need to look 4 at what we said yesterday, the totality of exposure. 5 Q. I understand, but your main focus, if you want 6 to know if the drug is causing this, would be on that 7 first month when you expect adverse drug reactions to 8 happen if they're going to; isn't that true, sir? 9 A. Again, only if you had a proper comparison, 10 such as the placebo group that wasn't receiving a drug 11 during the same time. 12 Q. And being a baseball fan, you understand why I 13 used the one and nine, don't you? I mean, aren't you 14 a step ahead of me? 15 A. No, sorry. 16 Q. Okay. I thought you were. We're going to talk 17 this afternoon about that baseball analogy you used 18 yesterday. If we're talking about an adverse drug 19 event and a person took the drug for nine months, we 20 need to talk about the first inning, not the whole 21 game, don't we? 22 A. No. 23 Q. Okay. We'll visit about that later. So 24 there's the DEN and the ADE. Dr. Tollefson, how 25 confident are you about the integrity of the way that PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1913 1 adverse drug events were recorded in the DEN, the Drug 2 Epidemiology Network, by people at Eli Lilly before 3 you came to the company? 4 A. Well, before I was there, it's difficult. I 5 would only offer the opinion that I assumed that they 6 did a good job. They tried to do their best. 7 Q. Are you aware of situations where people that 8 were asked to do this, that were asked to code these 9 things and say, is this suicide or is it overdose, is 10 it depression, to put the label on it that enables the 11 computer to pull it out at the back, where they were 12 saying, whoa, wait a minute. We're miscoding this. 13 We're putting garbage in. Are you aware of any 14 situation where somebody said that? 15 A. I did see one exhibit to that effect with one 16 individual, yes. 17 Q. Let's look at it. This is 117. November 13, 18 1990, we can go back and look -- I think you had it 19 right up there. If you wouldn't mind just looking and 20 telling us, is this about the same day when we have 21 that Leigh Thompson memo saying that priority number 22 one is to protect Prozac? 23 A. I think it was approximately the same time. 24 Q. Okay, sir. "This is regarding adverse drug 25 event reporting about suicide on Prozac." And the man PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1914 1 that writes this is named Claude Bouchy, correct? 2 A. Yes. 3 Q. And was he head of Lilly's operations in 4 Germany? 5 A. He was a businessman that was running the 6 German affiliate. 7 Q. Okay, sir. And he refers to another man named 8 Hans. Do you know who he's talking about? Hans 9 Weber, do you know who Hans Weber was? 10 A. He was, I believe at that time, in charge of 11 the medical division of that particular affiliate. 12 Q. So we understand when we read this, we're 13 reading the top businessman and the top medical man at 14 Eli Lilly in Germany that are writing this, correct, 15 sir? 16 A. Yes. 17 Q. "Hans Weber and I have problems with the 18 directions our safety people are getting from 19 corporate group drug epidemiology unit." Is that the 20 folks in Indianapolis? 21 A. Yes. 22 Q. "And requesting that we change the 23 identification of events as they are reported by the 24 physician." Does this mean that the physician reports 25 it as one thing and they code it as another? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1915 1 A. No. 2 Q. What does it mean to you when he says, "change 3 the identification of events as reported by the 4 physician"? 5 A. We're talking about two different things, I 6 think. I'd be happy to explain it. 7 Q. That's all right. We'll just look at what he 8 wrote. 9 A. All right. 10 Q. "On this one, our safety staff is requested to 11 change the event term, suicide attempt, as reported by 12 the physician to overdose. I want you to discuss with 13 me a minute, Dr. Tollefson, the significance of that. 14 If I were on Prozac and I attempted suicide by 15 hanging, by hanging, what these people were told to do 16 was code that in the computer as overdose, weren't 17 they? 18 A. I don't believe that's the case. I believe 19 that only suicide attempts by a drug, in which taking 20 a medication, were coded under that system to 21 overdose. If someone tried suicide -- this is my 22 recollection. If someone tried to commit suicide by a 23 non-pill method, it tracked to suicide attempt without 24 drug use or something similar to that terminology. 25 Q. What it tracked to, sir, was depression, didn't PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1916 1 it? 2 A. No, I don't believe that's correct, sir. 3 Q. Let's read on. "Hans has medical problems with 4 these directives -- directions and I have great 5 concern about it. I do not think I could explain to 6 the BGA," that's the German counterpart of the FDA, 7 correct? 8 A. Correct. 9 Q. "...to a judge, to a reporter, or even to my 10 family why we would do this, especially on the 11 sensitive issue of suicide and suicide ideation." You 12 think this man is troubled about what he's been asked 13 to do? 14 A. I think he's troubled because he apparently 15 doesn't understand how this system works within the 16 drug epidemiology unit, so it may have been a failure 17 for him to understand the process. 18 Q. Top businessman, top scientist, they just 19 didn't understand? 20 A. Well, number one, they obviously are not in 21 Indianapolis. They're in a relatively small German 22 affiliate, and as you pointed out earlier, the Drug 23 Epidemiology Network is based in Indianapolis, so they 24 may not have had familiarity with that process. 25 Q. Okay. We're going to look at what they say the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1917 1 next day or two after folks in Indianapolis try to 2 explain it to them. November 13th, 10:49 in the 3 morning is when this one starts. We look at the 4 second page, you'll see later. 5 Reading on, "I am" -- what is that word? 6 "Coding when an overdose is taken in a suicide 7 attempt, our research physicians prefer to list the 8 event term overdose even if, when tracking suicides, 9 we always look at all overdose and suicide attempt 10 reports." Now, that's what he was writing expressing 11 his concerns, correct? 12 A. I'm trying to understand that. He says, as I 13 look at it, when an overdose is taken in a suicide 14 attempt, our research physicians prefer to list the 15 event term overdose. That seems to make sense. 16 Q. Okay. Now, let's look, is it the same exhibit? 17 There's another exhibit that's November 14, the next 18 day, and this is Exhibit 118. This is Mr. Bouchy 19 again, okay, the following day regarding adverse event 20 reporting suicide. "Thank you very much for your 21 prompt answer and your detailed explanations. Hans 22 and I discussed the issue in depth." So clearly they 23 got an answer from Indianapolis, somebody has 24 explained it to them, right? 25 A. I haven't seen what the answer or the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1918 1 explanation was, so I don't know if it occurred or 2 not. Presumably it occurred by what he said. I don't 3 know if it was adequate enough to help educate him on 4 this. 5 Q. Well, let's see what they felt about it. 6 A. Okay. 7 Q. "Our point is the following: The physician has 8 reported a suicide. Do we have the right to change it 9 to some terminology which may -- which we may consider 10 to be more specific, for example, overdose, but which 11 is not free for ambiguity and could be regarded as 12 inaccurate or misleading?" Then they talk about the 13 term overdose not being free from ambiguity, and then 14 they say, "Finally, on a very simple and 15 non-scientific basis" -- this is Claude Bouchy, the 16 businessman, talking here, right, non-scientific? 17 A. It appears that way, um-hum. 18 Q. "...I personally wonder whether we are really 19 helping the credibility of an excellent adverse drug 20 event system by calling overdose what a physician 21 reports as a suicide attempt and by calling depression 22 what a physician is reporting as suicide ideation." 23 Physicians' reports -- I got a patient who took 24 Prozac, became -- got suicidal ideation. Say that guy 25 is Jonathan Cole or Martin Teicher and they report on PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1919 1 one of those cases, suicide ideation, that's what 2 happened, but these men were told to record that as 3 depression? 4 A. It is a symptom of the disease. 5 Q. So what they were told to do was record it in a 6 way which will blame the underlying disease, weren't 7 they, sir? 8 A. No. I think you probably don't understand. 9 You mentioned earlier the 1639 form. Let me point out 10 there are three things that, essentially, go to the 11 FDA, number one, exactly what the physician said goes 12 to the FDA. The term the physician used, whatever it 13 was, goes to the FDA. The coding process is a process 14 that's been set up by regulatory agencies, and the 15 reason they set up this coding, it's like a category, 16 and they have said when you have physicians describing 17 an adverse reaction, they might use a number of 18 different terms and if you only collected those 19 individually, you would actually lose a sense of how 20 many of those events were occurring. So they have 21 created categories, such as overdose where these 22 become lumped together so that you get a true 23 appreciation of how often something is occurring 24 despite the individual different terms the doctor 25 might use. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1920 1 So the FDA sees the individual physician's 2 comment, the term that the physician used, and how it 3 maps to this larger category. 4 Q. Dr. Tollefson, I couldn't agree with you more, 5 but when you do an analysis, a meta-analysis, when you 6 punch the button on the computer to have the computer 7 spit it out to you in categories, it relies on the DEN 8 coding, doesn't it, sir? 9 A. Certainly, but the coding allows you to go back 10 and look at any of those individual event terms as 11 well. 12 Q. I agree with you. 13 A. And what it provides you is an opportunity to 14 not miss things. 15 Q. I don't agree with you there. Let's go on. 16 "We fully realize that there is no code in our Drug 17 Experience Network system for suicide ideation." Now, 18 I want to stop this sentence right there and we'll 19 finish it in a minute. Why, why in the world, when it 20 was nine months since the Teicher article came out, 21 since 20/20, since ABC News, since Nightline, since 22 The Wall Street Journal, why hadn't Lilly implemented 23 a term for suicidal ideation so that they could track 24 this phenomenon and see what was happening? 25 A. I think you missed my point. It's very easy to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1921 1 track the term. 2 Q. Excuse me, Doctor, I am not interested in your 3 point. I'm interested in you answering my question. 4 Why did Lilly not put a term in your computer in light 5 of this public interest? In light of the gravity of 6 the situation, why didn't they put a term so that when 7 someone hit a button, they could retrieve this data 8 according to the way it was reported by the physician? 9 A. They did, sir. 10 Q. Well, that's not what this man says, is it? 11 A. Well, this man, perhaps, isn't aware of the 12 computer system in Indianapolis, but that system does 13 exist to do exactly what you proposed. 14 Q. "We fully realize that there is no code in our 15 DEN for suicide ideation, but it could be argued by 16 people who have little sympathy for the company or by 17 regulatory authorities that it is not a responsible 18 way to deal with an issue which is getting so much 19 attention in the scientific and in the general press. 20 It could also be argued that the term depression is 21 not specific in this case." 22 What he is saying is exactly what 23 Dr. Heiligenstein and Dr. Beasley told Dr. Thompson 24 two months earlier, don't blame it on the underlying 25 disease, boss. Don't do that. Isn't that true, sir? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1922 1 A. No, sir. 2 Q. "Of course, at the end of the day, we will do 3 what we're told to do, but Hans and I felt we had to 4 bring these points to your attention." Did they, in 5 fact, do what they were told to do by the people in 6 Indianapolis? 7 A. I would suspect, yes. That is, to use the 8 system as it has been created, including the FDA's 9 system for reporting adverse events. There is a 10 common reporting mechanism and I would assume that 11 they had followed it. 12 Q. All right, sir. Have you reviewed the other 13 documents that are in evidence for the jury pertaining 14 to this issue of categorization of the information in 15 the Drug Epidemiology Network? 16 A. I have seen some. 17 Q. There are one or two I want to show you. 18 A. Okay. 19 Q. We're going to start with Plaintiffs' 20 Exhibit 71. 21 MR. VICKERY: Mr. See, are you ready? 22 MR. SEE: Yes, sir. Thank you. 23 Q (By Mr. Vickery) Let's get the date on this, 24 Ms. Barth. This goes all the way back to 1986, four 25 years before, right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1923 1 A. Yes. 2 Q. And you're aware, are you not, sir, that in 3 early 1985, the BGA rejected or gave a preliminary 4 rejection of Prozac in the Federal Republic of Germany 5 for two reasons, one of which was the high number of 6 suicides? Are you aware of that? 7 A. My recollection, I thought there were 18 8 questions that had been raised, one of them had to do 9 with suicide -- absolute numbers of suicide rates. 10 Q. That's later. I'm talking about January of 11 1985 when they first specifically said, we're going to 12 reject this drug. This is just fair warning, early 13 warning, we're going to reject it for two reasons, one 14 of the two was suicide. Are you not familiar with 15 that? 16 A. I don't believe I've seen it. 17 Q. I'll give you that opportunity after lunch. 18 And way back in 1986 someone was saying -- who is this 19 that's saying this, Ms. Barth? Joachim Wernicke, that 20 man is not over in the Federal Republic of Germany, 21 he's named in -- 22 A. Yes. 23 Q. And tell us who Dr. Wernicke is? 24 A. He's a physician involved with Prozac at that 25 time. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1924 1 Q. How high up the corporate ladder is he? 2 A. Not very. 3 Q. Okay. It's regarding fluoxetine suicide, 4 Prozac suicide. "It would appear that all the cases 5 which you already have," except blank and blank, 6 "occurred before DEN," in other words, before the Drug 7 Experience Network, right, Drug Epidemiology Network? 8 A. Um-hum. 9 Q. "And that the others on my list occurred after 10 the original submission. This seemed logical and 11 maybe true, but I'm not sure. In the early days, the 12 criteria for DEN reports were not as strict as they 13 are now, so I'm not sure that what was put on the list 14 of suicide attempts necessarily got into DEN." 15 Now, when Dr. Beasley analyzed this data, when 16 he did his meta-analysis and looked back, he looked 17 back at data that preceded the Drug Epidemiology 18 Network, he looked back at data that Dr. Wernicke said 19 didn't include all the suicide attempts; isn't that 20 true, sir? 21 A. No, I wouldn't make that. That was five years 22 before Dr. Beasley's work, and I would assume that 23 this -- as it points out, there was an increasing 24 effort to do more of a strict adherence. I suspect 25 that those things were incorporated into DEN over PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1925 1 those five years. It looks like Dr. Wernicke is 2 bringing this out as a point and I would assume they 3 were included. 4 Q. You think that even though he said, it didn't 5 get in, that sometime in the intervening four years, 6 somebody put it in, is that what you're saying you 7 think happened? 8 A. I'm sure they were accounted for. That would 9 make sense. 10 Q. Okay. That sort of brings me to the topic 11 of -- 12 THE COURT: Are you going to be much longer 13 with this witness? 14 MR. VICKERY: Probably about one more hour, 15 Your Honor. 16 THE COURT: All right. I think we better break 17 for lunch now. Please be back at one. 18 (Whereupon, a lunch recess was taken from 19 12:00 p.m. to 1:15 p.m.) 20 THE COURT: Please proceed, Mr. Vickery. 21 MR. VICKERY: Thank you, Your Honor. 22 Q. Dr. Tollefson, I want to show you Exhibit 124 23 from April 23rd of 1991. That's about two months 24 before you joined the company, correct? 25 A. Yes. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1926 1 MR. SEE: Just one second, please. 2 THE COURT: What number are you on? 3 MR. VICKERY: 124. Your Honor, this exhibit is 4 one in which the Court had ruled that the exhibit 5 doesn't come into evidence, but I could cross-examine 6 the witness about it, and what I want to do is show 7 the exhibit and cross-examine him about it. Mr. See 8 is not sure about it. 9 MR. SEE: I think Your Honor excluded the 10 exhibit from evidence. 11 THE COURT: Better go on to another exhibit at 12 this point. 13 MR. VICKERY: Okay. 14 Q. You said earlier that the Ham-D Scale was like 15 that little gold Kodak film, the gold standard, right? 16 A. That's correct. 17 Q. Now, I want to look at what some of your 18 colleagues at Lilly have said about that. Exhibit 69. 19 This is July 1986, and we have a horrible copy of it 20 and we'll see if we can zoom in on it. Back in '86 21 the Germans were concerned about suicide, but it 22 hadn't become a live issue in the United States; is 23 that right? 24 A. I think the information would have been 25 provided to both German and FDA authorities. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1927 1 Q. Okay. This is Dr. Wernicke. What kind of 2 doctor is Dr. Wernicke? 3 A. Neurologist. 4 Q. Okay, sir. And a board certified neurologist? 5 A. I don't know. 6 Q. That's the same board that certifies neurology 7 that certifies psychiatry, right? You're board 8 certified in neurology and psychology, aren't you? 9 A. Psychiatry not psychology. Psychiatry is the 10 practice of medicine. Psychology is not. 11 Q. I'm sorry, I misspoke. Neurology and 12 psychiatry, they're the same board? 13 A. Different examines though, but yes, under the 14 same auspices. 15 Q. "The suicide factor on the Ham-D does not 16 provide an accurate predictor, thus we do not advocate 17 that it be used in place of the investigator's 18 judgment." 19 Now, if Eli Lilly knew back in 1986 that the 20 suicide element on the Ham-D was not a very reliable 21 predictor, that they should use the investigator's 22 judgment, then please tell us why between that time 23 and 1990, A, you didn't start using some different 24 scale, and B, that Dr. Beasley just used the Ham-D and 25 ignored the investigator's judgment? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1928 1 A. Well, there are several questions or responses 2 in there. Number one, I think I said very clearly 3 yesterday that we, in the field in general, do not 4 consider the Hamilton to be a predictive instrument. 5 No one can effectively predict suicide as accurately 6 as we would like. So it is a predictive tool. 7 It is a tool that looks at a snapshot in time 8 as we talked about. It involves the physician's 9 judgment. It is the physician who carries out what we 10 call a semi-structured interview, dialog with the 11 patient, rates the scale, and they can look at point A 12 versus point B in time and make comparisons, point A 13 versus point B. That's much different than saying 14 point A predicts what might happen four years from 15 now. So it is not a predictive scale. The second 16 point is Dr. Beasley did not rely exclusively on the 17 Hamilton in his paper. 18 Q. Oh, he didn't? 19 A. He did not. 20 Q. What else did he rely on? 21 A. It's very clearly stated in the methods of 22 Dr. Beasley's paper that he used the DEN system, he 23 used the Hamilton, and he used an electronic search of 24 the case report form filled out by the investigator 25 who was dealing with the patient, three sources. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1929 1 Q. This DEN system is one we were talking about 2 earlier where, at least, Mr. Bouchy and Dr. Weber in 3 Germany were very concerned about what was the quality 4 of the information going into it, right? 5 A. They expressed that, and I think it also 6 reflects why Dr. Beasley used three different systems 7 as a fail safe to make sure that, indeed, all of those 8 events would be captured. 9 Q. Let's look at what Dr. Beasley himself, and 10 other people writing for him, said about the Ham-D in 11 response to Dr. Healy's criticism of this 12 meta-analysis. This is Exhibit No. 130. "Suggested 13 five points to Oswald and Healy and Creaney." Now, 14 this is a draft of Dr. Beasley's response, but 15 ultimately there was a published version. We're going 16 to look over on the second page, Ms. Barth. 17 "The letter by Healy and Creaney makes a number 18 of interesting points which perhaps highlight the need 19 to include additional measures in future trials with 20 new drugs of this class. They suggest that Item 3 of 21 the Hamilton Rating Scale is an insensitive measure of 22 suicidality. This may, indeed, be the case, but was 23 the only data available." 24 That's the only data available to Dr. Beasley 25 because they went back and looked back at what had PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1930 1 been done earlier; isn't that true, sir? 2 A. Two points. Number one, no, it is not true, 3 and number two, I don't believe that this is 4 Dr. Beasley's letter. 5 Q. It is a draft of a letter that was ultimately 6 sent by Dr. Beasley to the journal in evidence. 7 A. My only point would be, it's not signed. I do 8 not believe this comes from Dr. Beasley. I suspect it 9 comes from someone, I don't know who, in the United 10 Kingdom, given the spelling of randomized with an S. 11 Q. We've already crossed that hurdle. It's in 12 evidence, and I think you're right. Somebody in the 13 United Kingdom drafted this for Dr. Beasley. 14 A. So we could look at Dr. Beasley's response, but 15 this would appear to be a draft of someone in the U.K. 16 Q. Someone in the U.K. that worked for Lilly? 17 A. I don't even know the answer to that, sir. 18 Q. Okay. 19 A. There's no name on it. 20 Q. Let's look down lower on this draft. "It is 21 clear, however, that the focus of the relationship 22 between suicidality and akathisia is an important one 23 and has been debated in the literature for years. The 24 association between antidepressants, including 25 fluoxetine or Prozac, and akathisia has been reviewed PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1931 1 by Lipinski." Now, that's one of the numerous 2 articles that you cited in 1992 as articles on the 3 other side of this issue, correct? 4 A. I apologize, I was having -- as you moved it on 5 the screen, I was having trouble finding it on the 6 hard copy. I think I have. Could you start again, 7 though, please. 8 Q. Sure. "It is clear, however, the issue of the 9 relationship between suicidality and akathisia is an 10 important one and has been debated in the literature 11 for some years. The association between 12 antidepressants, including Prozac, and akathisia has 13 been reviewed by Lipinski." That is an article, the 14 Lipinski article, that you cited, when you cited -- 15 remember that was number seven through number eighteen 16 that we looked at this morning? 17 A. Yes. 18 Q. That was one of the ones you cited, correct? 19 A. Yes, it is. 20 Q. "There was no specific rating scale for 21 akathisia included in the trial designs for the 22 studies reported, so the only source of data would be 23 adverse event reports. Akathisia is a subjective 24 phenomenon, and hence, would rely on patients 25 volunteering information." PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1932 1 Now, these adverse event reports are the very 2 things that you say can't be used to prove causation, 3 right? 4 A. That's correct. 5 Q. Now, if they can't be used to prove causation, 6 neither may they be used to disprove causation; isn't 7 that true, sir? 8 A. No. I think, if you're talking about on an 9 individual patient, then it's correct, they could not 10 be used to prove or disprove. If you're talking about 11 comparisons of larger populations, such as the 12 meta-analysis conducted by Dr. Beasley, it does then 13 permit the ability to assign probable causality. So 14 it's the difference between one person versus a large 15 group of people in comparison groups. 16 Q. So let me make sure I understand your position 17 real clearly on this. If we're talking about large 18 numbers of people, large numbers of adverse reports, 19 even though they're anecdotal reports and they're in 20 the Drug Epidemiology Network, then that data can be 21 used, either by you or by us, to either prove or 22 disprove the causal relationship. Is that your 23 testimony? 24 MR. SEE: Your Honor, I object and that the 25 Court has already ruled on the question. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1933 1 THE COURT: Let's have a side bar. 2 (Whereupon, the following proceedings were had 3 at side bar out of the hearing of the jury.) 4 MR. SEE: The point of our motions in limine 5 was to exclude the spontaneous adverse reactions as 6 evidence of causality, and that was granted, that 7 experts could not rely upon spontaneous reports for 8 causality, and now Mr. Vickery is asking the very same 9 question. 10 MR. VICKERY: Well, Your Honor, with all due 11 respect to Mr. See, I assume that he apprised his 12 witness of the ruling in his favor on the motion in 13 limine that he asked for. He asked that we not be 14 able to use adverse drug event reports to prove 15 causation, and when I asked this witness about two 16 months ago, isn't it true that you cannot use those to 17 prove causation, the witness, instead of following the 18 Court's order, following the ruling, said, oh, no, you 19 can use them. 20 MR. SEE: That's not what he said. 21 MR. VICKERY: As I remember and I'm sure the 22 Court's good recollection, which is better than either 23 of ours, remember that when Mr. See's witness gave 24 evidence to the contrary to Mr. See's motion in limine 25 and said, oh, yes, we can use them, but I can't -- I PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1934 1 thought he would say, in all honesty, no, you can't 2 use those reports to prove or disprove causation. I 3 thought he would say that because that's been his 4 deposition testimony and that's what they secured from 5 the Court, but he didn't say that. 6 MR. SEE: Your Honor, if I might, you will 7 recall what the doctor just said, you can't use 8 adverse reaction reports in a patient to determine 9 causality when you have large groups of patients and 10 you have two different groups. When you have a 11 comparison of one group to another, then maybe you can 12 use reports of side effects in order to get causality. 13 He was not saying you can use spontaneous reports. 14 That was not his testimony. He didn't say that. 15 MR. VICKERY: This is a suggested solution, the 16 Court can ask, can you use them or not use them, and 17 you'll get a straight answer from this man and we'll 18 go on based on this. 19 THE COURT: Why don't I instruct the jury that 20 the spontaneous reportings cannot be used -- 21 MR. SEE: That's fine. 22 MR. VICKERY: But he just testified otherwise. 23 THE COURT: Pardon me? 24 MR. VICKERY: We disagree on what he said. 25 THE COURT: Whether he testified that way or PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1935 1 not, there was a prior order that he cannot use them 2 for that purpose. 3 MR. VICKERY: Which if he just testified, as I 4 say he did, it's contrary to the order. 5 THE COURT: We'll strike his testimony to the 6 contrary. 7 MR. VICKERY: If you will instruct him, any 8 testimony to the contrary -- 9 MR. SEE: There's nothing to strike. 10 MR. VICKERY: I think there is. 11 THE COURT: I will strike any testimony that 12 the spontaneous reportings can be used to find 13 causation. 14 MR. VICKERY: Fine. 15 MR. SEE: Fine. 16 (Whereupon, the following proceedings were had 17 in open court in the presence of the jury.) 18 THE COURT: The Court will instruct the jury 19 that spontaneous case reports cannot be used to show 20 causation and any testimony to the contrary is 21 stricken. Does that satisfy both counsel? 22 MR. VICKERY: That's exactly fine, Your Honor. 23 MR. SEE: It does, Your Honor. Thank you. 24 Q (By Mr. Vickery) So what the Court's just 25 instructed is that Dr. Beasley cannot use adverse PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1936 1 reports in the Drug Experience Network to prove or 2 disprove causation. You accept that, don't you? 3 MR. SEE: Your Honor, I have to object to the 4 question because the question is misleading. 5 THE COURT: I'll sustain the objection. Let's 6 move on. 7 Q (By Mr. Vickery) Okay. Let's just look at 8 the last paragraph, "There's considerable interest in 9 the mechanisms in underlying the associations between 10 suicidality, impulsivity, aggression, and akathisia. 11 It seems unlikely that even if the flames of media 12 hype are doubts, academic interest will permit real 13 phenomenon to be obscured and go unheeded." This is 14 the draft that ultimately became the letter. You've 15 seen the letter, haven't you? 16 A. No, I do not believe -- this was not 17 Dr. Beasley's draft. This did not become -- 18 Dr. Beasley had his own draft. I have no idea who 19 submitted this, even if it was a medical person. 20 Dr. Beasley does his own work. He did write a letter 21 to the editor. We could look at that letter to the 22 editor. This does not represent Dr. Beasley's work 23 nor Dr. Beasley's thinking, to the best of my 24 knowledge. 25 Q. Would you accept Ms. Mangrum's word on it PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1937 1 instead? 2 A. Pardon me? 3 Q. Would you -- 4 MR. SEE: Your Honor, I object to the question. 5 I ask it be stricken. 6 THE COURT: Sustained. It will be stricken. 7 MR. VICKERY: Well, I would like to be heard 8 about it, Your Honor, then at side bar. 9 THE COURT: All right. 10 (Whereupon, the following proceedings were had 11 side bar out of the hearing of the jury.) 12 THE COURT: We have too much time at side bar. 13 MR. VICKERY: I agree. This is the first time 14 in this whole trial that I've asked to do this. I 15 don't mean to try the Court's patience, but when we 16 had a long hearing on these exhibits, the Court asked 17 Ms. Mangrum about this letter, about this draft -- 18 THE COURT: What exhibit are you on? 19 MR. VICKERY: I'm on Exhibit No. 130. The 20 Court asked Ms. Mangrum about Exhibit No. 130, and she 21 represented to the Court that this, indeed, was a 22 draft of the letter ultimately signed by Dr. Beasley. 23 She told the Court it was a draft by Lilly employees 24 in the United Kingdom, and that on the basis of this 25 representation, the Court admitted the document. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1938 1 MR. SEE: And what different has happened? 2 MR. VICKERY: What different has happened is 3 this man said, oh, no, this wasn't a draft of 4 Dr. Beasley's letter at all. The draft of 5 Dr. Beasley -- 6 THE COURT: He didn't say it wasn't 7 Dr. Beasley's letter. He said he didn't think it 8 represented Beasley's thinking. 9 MR. SEE: He didn't think Beasley wrote it, 10 which is exactly what she said. 11 MR. VICKERY: I thought he said this was not a 12 draft of Beasley's letter. 13 THE COURT: I don't think he did. 14 MS. MANGRUM: He said it doesn't represent 15 Beasley's work. It wasn't written by Beasley. He 16 doesn't know who it was in the U.K., but obviously 17 it's not his work. That's what he said. 18 MR. VICKERY: But counsel has represented to 19 the Court that it was a draft of the letter that 20 became the Beasley letter by people in the United 21 Kingdom, and this man is trying to disallow 22 representations that Ms. Mangrum has made to the 23 Court. 24 THE COURT: I don't recall that specific 25 representation, but this appears to be a draft of the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1939 1 Beasley response. I think the witness testified he 2 thought it was a draft of a letter from Beasley, but 3 it did not represent his thinking. 4 MR. VICKERY: I don't remember it that way, but 5 it's not a matter of point to take up your time. 6 THE COURT: One other thing, 1124 -- I lost my 7 place here -- you could use that for 8 cross-examination. 9 MR. VICKERY: You're absolutely right, Your 10 Honor, we made an error on that and we'll use it for 11 cross-examination. 12 MS. MANGRUM: Of Dr. Thompson. 13 THE COURT: Of who? 14 MS. MANGRUM: Dr. Thompson. 15 THE COURT: You're not bringing Thompson here. 16 MS. MANGRUM: Exactly. That's right. 17 THE COURT: I don't think I said Dr. Thompson. 18 I think I just said cross-examination. 19 MS. MANGRUM: I have that written down and 20 that's the basis of me saying that, Your Honor. 21 THE COURT: Are you going to bring Thompson? 22 MR. SEE: No. 23 THE COURT: You can cross-examine. 24 MR. VICKERY: While we're all here, Mr. See and 25 I discussed over the lunch break there is a segment PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1940 1 from this man's deposition that I want to offer 2 videotape for rechallenge, but because Mr. See and I 3 have a disagreement about whether it is impeachment, I 4 can give you the pages and lines of it and the Court 5 can simply look at it and say yes, it is or no, it's 6 not. 7 THE COURT: When do you want to do it? 8 MR. VICKERY: That's the reason I wanted to 9 tell you now. I didn't want to come over here for 10 another trip over here. I can give you the pages and 11 lines now if you want to look at them while you're 12 doing this. You may not want to be distracted while 13 we're doing this. It is about six pages. 14 THE COURT: Six pages? 15 MR. SEE: It is not impeachment. 16 MR. VICKERY: I can cut it down to three. 17 THE COURT: You better do it during the break. 18 (Whereupon, the following proceedings were had 19 in open court in the presence of the jury.) 20 THE COURT: Please proceed, Mr. Vickery. 21 MR. VICKERY: Thank you, Your Honor. 22 Q. We're going to look at 1124 now, the one I 23 handed you. Let's look at the top, Ms. Barth, and 24 we'll get the date. This is April 22, 1991, right? 25 A. Yes, sir. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1941 1 Q. A couple months before you joined the company, 2 right? And this is Dr. Thompson. You can tell from 3 the first paragraph that he's getting a reply ready 4 for ABC Prime Time Live, okay, sir. And we're going 5 to look specifically at the third point. Ms. Barth, 6 can you zoom in on the third point there. 7 Okay. If you would just read along with me, 8 "Third point, we need some documentation of studying 9 suicidal patients. I went through all the data from 10 the 3,055" -- is that what that is -- 3,065," those 11 are the 3,065 patients that Dr. Beasley studied in the 12 meta-analysis, correct, sir? 13 A. That's a likely conclusion. 14 Q. "That that didn't suffice. Somebody had told 15 her we used the Ham-D to exclude the most depressed 16 patients. I told her we had inpatient studies at the 17 time of the launch." Now, we talked about yesterday 18 that the most inpatient studies you had were from 19 Europe, right? 20 A. Correct. 21 Q. "What I'm not sure of is what we had" -- I'm 22 sorry, "is what we can describe in terms of studies of 23 suicidal patients other than the 3,065 at the time of 24 the launch and now. I did not share the European data 25 at all." All caps. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1942 1 Now, if the inpatient studies were done in 2 Europe and if Dr. Thompson was trying to be candid and 3 open on this issue, why wouldn't he have shared the 4 European data? I mean, he capitalized the word not 5 and put the words at all, that's pretty emphatic, 6 isn't it? 7 A. I'm sorry, could you restate your question? 8 Q. When somebody puts something in all capitals, 9 do you think that means they're trying to emphasize 10 what they're saying? 11 A. I'm sure that's one possibility. Probably. 12 Q. Okay. Well, do you think that maybe the reason 13 he didn't share that European data at all was because 14 the European data showed, among other things, that the 15 German government had denied or given preliminary 16 denial based on the high rates of suicide? 17 A. No. I would say two things, one possibility is 18 he didn't have that data at his fingertips. So he 19 didn't have it available to him. He may not have 20 known that particular data, at least not have it 21 committed to memory. The European data, though, has 22 been subsequently published in an analysis that I 23 conducted and it was corroborative of the U.S. data. 24 Q. Incidentally, talking about the foreign 25 countries, and you had this big chart of all the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1943 1 countries that Prozac is sold in, Dr. Healy said it's 2 not sold in Japan, and it wasn't on your chart. 3 That's true, isn't it, it's not sold in Japan? 4 A. It is not approved for marketing. It is used 5 in Japan under a special license, and the growth in 6 Japan of its use has been really quite staggering of 7 late. So it is available to physicians. They do have 8 to go through a special procedure to obtain it, but it 9 is being used by Japanese patients with depression. 10 In fact, we have had dialog with the Ministry of 11 Health about registering the product there. They have 12 interest in seeing it registered in Japan. 13 Q. Do you have salespeople over there encouraging 14 those doctors to jump through those hoops -- 15 A. No. 16 Q. -- and prescribe it? 17 A. No. It's the physician's interest in the 18 product. 19 Q. Now, I want to talk to you briefly about this 20 document that was the 5.6 times higher, and let's put 21 it in sequence. In January of 1985, the German BGA 22 rejected Prozac for registration there for two 23 reasons, one of which is suicide. And remember, we 24 talked before lunch about that and you weren't sure 25 whether it was 2 or 18? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1944 1 A. I do. 2 Q. Were you able to determine over the lunch hour 3 whether, indeed, I was correct, that it's two? 4 A. I did not. 5 Q. Let me show you the document then from January 6 of '85. This is Plaintiffs' Exhibit 53. 7 MR. VICKERY: Mr. See, you with me? 8 MR. SEE: Yes, sir, I am. Thanks. 9 Q (By Mr. Vickery) "January 29, 1985. We 10 unofficially received our confirmation that Prozac was 11 discussed by the Commission A at the BGA on 12 January 21st. Two major concerns seem to be the 13 reason that the registration was not accepted. One, 14 efficacy questions. This may be due to the 15 experiences and study design and classifications used 16 in the United States versus Germany." Efficacy 17 questions means whether it works, right, whether it 18 helps people? 19 A. Yes. 20 Q. "Two, suicidal risk." Now, in response to this 21 in January of '85, Eli Lilly went out and hired an 22 opinion leader, a guy named Professor Herman, I think 23 his name was pronounced, and I promised to show you 24 the memo about him being an opinion leader, so let me 25 do that. The exhibit is 59. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1945 1 MR. VICKERY: Your Honor, I've withdrawn that 2 exhibit. 3 Q. Can you tell me -- I'm sorry, I made a mistake. 4 Only the second one today. Professor Herman did two 5 reports. He did a preliminary report by the end of 6 March, March 29th, and then he took nearly a couple of 7 months to finalize his report, and you've seen both of 8 those, haven't you? 9 A. Yes. 10 Q. We're going to look at both of them very 11 briefly. One of them, the preliminary report is dated 12 March 29, 1985, and it's in evidence as Plaintiffs' 13 Exhibit 58. "Preliminary report, March 29th regarding 14 the benefit/risk consideration according to the state 15 of knowledge on March 29, 1985, concerning the 16 antidepressant drug fluoxetine or Prozac." Now, this 17 is a long document, but we won't go through it, but 18 this is the one that resulted in him saying purely 19 mathematically it's a 5.6 times higher risk of suicide 20 on Prozac than on Imipramine. You're aware of that, 21 aren't you? 22 A. Yes. 23 Q. Now, you went through, yesterday, this baseball 24 analogy with Mr. See, and you told us that once you 25 account for all of the patient days, once you PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1946 1 converted to all the patient days, that it all came 2 out even, came out even in the wash. Who's done that 3 and when did they do it? 4 A. That data was, I would presume, evaluated by 5 the BGA because the drug was clearly approved in 6 Germany without specific labeling around the product 7 safety question, and it's still marketed today in 8 Germany, so I would assume that the BGA saw those 9 analyses. 10 Q. I'm sorry, I thought when you all were going 11 through that whole baseball thing yesterday, that you 12 were telling us -- I mean, Mr. See asked you, if I 13 recall correctly, once you take into account the 14 patient days, do they come out even? And I thought 15 your sworn testimony was, yes, they do. Am I wrong or 16 is that your testimony? 17 A. The patient days do not come out even. There 18 were more patient days with fluoxetine. The rates per 19 patient day were non-significantly different from one 20 another. 21 Q. On what do you base that? What I'm asking is, 22 where is the analysis of that? You just say it, but 23 is there any way that we can sort of double-check you 24 if we were so inclined? 25 A. I think if we had a statistician here, I PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1947 1 suppose he could actually do the statistical 2 significance. We could look at the absolute numbers. 3 Q. In the 14 years since Professor Herman's 4 report, has Lilly gone back to do that statistical 5 analysis to tell us that, so that we can look at it 6 and, you know, check ourselves and see if it was done 7 properly or do we simply have to trust you and say, 8 oh, yeah, if you do it, it worked out that way? 9 A. No. The analysis has been done. I have seen 10 it and it revealed no statistically significant 11 difference between the tricyclics and Prozac. 12 Q. Who did it and when? 13 A. I believe it was done by Mary Saylor. I don't 14 know the exact date. It may well have been done even 15 prior to that, but I'm aware that Mary Saylor, one of 16 Lilly's statisticians has done that calculation. 17 Q. And was it done in anticipation of this trial, 18 is that why it was done? 19 A. I would imagine that she has relooked at that 20 information in anticipation of the trial. Again, 21 though, I think one point that maybe isn't clear here 22 is that when one is having a dialog with a regulatory 23 agency, there are processes of back-and-forth 24 questions and provisions of additional data and the 25 regulatory agency has their own statisticians that are PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1948 1 highly capable to conduct analyses, and I would assume 2 the BGA has conducted their own analyses that led to 3 their decision to approve of Prozac in Germany. 4 Q. Let's look at the conclusion in the preliminary 5 report by Professor Herman. I think it's on Page 22 6 of this exhibit. "The benefits versus risk 7 consideration for Prozac currently does not fall 8 clearly in favor of the benefits. Therefore, it is of 9 greatest importance that it be determined whether 10 there's a particular subgroup of patients who respond 11 better to Prozac than to Imipramine so that the higher 12 incidence of suicide attempts may be tolerable." 13 Now, I want to ask you, sir, given your 14 position at Eli Lilly, is there any number of suicide 15 attempts related to this drug that would be tolerable 16 to Eli Lilly? 17 A. No. 18 Q. Okay. Now, that was what he -- the way he 19 balanced the risks in March of '85, the risks and the 20 benefits, was to say, let's see if there's a smaller 21 group of patients. Let's not try to sell it to all 22 the patients. Let's see if there is a smaller group 23 that could benefit from it, and that way that might 24 make this suicide number tolerable. That's what he's 25 saying there, right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1949 1 A. That's your interpretation of what he's saying 2 there. I guess my opinion would be, this was a 3 consultant, not a Lilly employee, who has a 4 preliminary opinion, probably not having seen all of 5 the data, who was raising a question. Now, what would 6 be the question relevant at that time? Imipramine, 7 one of the older tricyclics, is a very dangerous drug 8 and patients overdose with it. It could be fatal if 9 you take two, three, four days of the medication at 10 one time. I suspect what he is trying to get a sense 11 of is we know how lethal Imipramine is in an overdose. 12 We have this information regarding Prozac and suicide 13 attempts not completed, but attempts, and he's trying 14 to put it in perspective of looking at the two drugs, 15 trying to see what their relative strengths or 16 weaknesses might be in his preliminary consultation. 17 Q. And as lethal as Imipramine is, what he found, 18 according to the worldwide state of knowledge, as of 19 March of '85, was that if you just look at the math, 20 Prozac was 5.6 times more likely to produce a suicide 21 attempt than Imipramine, didn't he, sir? 22 A. Only if he failed to consider the exposure days 23 of patients. The fact that Prozac patients were 24 treated for many, many more days with their illness 25 than their Imipramine counterparts. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1950 1 Q. Now, can you explain for us why it is that this 2 opinion leader, this experienced man that Lilly hired, 3 in a 22-page document would have made such an 4 omission, would have failed to take that into account, 5 the patient days? 6 A. He may not have thought of it. It may not have 7 been his specialty. He may not be an epidemiologist. 8 Was it in his final report? 9 Q. Yes, sir, it was. That's just the thing I was 10 going to bring up to you. All of what you say, I 11 would agree with totally, but he had two months 12 between this and his final report to get feedback from 13 Lilly and go do what you're criticizing him now for 14 not doing, figuring the patient days. So why is it, 15 given those two extra months before his final report, 16 do you have any explanation for why this guy wouldn't 17 have done that? 18 A. Well, I think you may fail to understand the 19 process of getting a consultation. Someone comes in 20 as a consultant, they have a certain amount of 21 information they look at. They reach an opinion. 22 They write a draft. Then there's a chance to discuss 23 it and make sure that they have all the data, the 24 totality of the data to look at. I'm sure that was 25 done when Professor Herman completed his final report, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1951 1 at least as I recall it. I don't believe that this 2 type of statement was in his final report. When he 3 saw the data, consistent with the baseball analogy, he 4 realized that he had to look at patient exposures. He 5 couldn't get caught up in just looking at an absolute 6 number, A versus B. 7 Q. Well, his final report, I assure you, still has 8 the 5.6 number in it, okay, but I agree with you that 9 his bottom-line conclusion isn't the same. Before we 10 turn to that, tell us if you would -- and this is a 11 real technical question, but tell us as simply as you 12 can so that even I can understand, the difference 13 between endogenous and exogenous depression? 14 A. Well, first of all, it's a very archaic term. 15 It's no longer used, but probably 20 -- 15 to 20 years 16 ago, at least. Those terms were used back before we 17 knew more about the biology of depression. And at 18 that time people would say certain people would 19 develop depression with no apparent life event stress. 20 In other words, it just kind of came out of the blue, 21 and those were referred to as endogenous. Thence, 22 they would also look at some people who appeared to 23 become clinically depressed in the midst of 24 significant environment stressors; marital problems, 25 could be relationship issues, loss of job, et cetera. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1952 1 Those were called exogenous. 2 However, subsequently, and I'd cite the 3 American Psychiatric Association which has the 4 textbook on diagnosis, became recognized that it 5 really didn't matter that initial cause of the 6 depression. Once the disease developed or the 7 depressive syndrome was present, it looked the same 8 whether it started internally or externally, it was 9 the same disorder. So in today's schema, we don't 10 talk about exogenous or endogenous depressions. We 11 talk about depression, and then if there are 12 environmental factors, those are subject for 13 psychotherapy or other kinds of interventions to help 14 a patient recover. 15 Q. And the reason I asked that, and thank you for 16 the explanation, is that's what he was talking about 17 doing, limiting the class of people who would be 18 getting Prozac. That's his first reaction in March, 19 isn't it? 20 A. But not in his final report. 21 Q. I agree with you. But, of course, if you 22 limited the class of people that would get it, and 23 that's fewer people that can buy your pills; isn't 24 that true? 25 A. Not necessarily. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1953 1 Q. Why not necessarily? I don't understand. 2 A. Well, it's possible that if you had some 3 exclusive labeling around a particular group of 4 patients where you were extraordinarily effective, you 5 might get 100 percent of those patients; whereas, if 6 you didn't have that labeling specifically, you might 7 only be getting 10 percent of the whole. 8 Q. Okay. But if there's a whole and if we limited 9 it to a subclass of it, generally speaking you've got 10 fewer people that can buy your drugs, isn't that true, 11 unless, as you say, all of the ones in that subclass 12 buy it? 13 A. That's fine. 14 Q. Okay. Now, let's look at his final report. It 15 is Defendant's Exhibit 1116. 16 MR. VICKERY: I don't have the original of that 17 one, Your Honor, because it's not my exhibit. 18 Q. Can you see pretty good from there? 19 A. No. Well, it depends. I'll try. I'll let you 20 know if I can't. 21 Q. On Page 26 -- the report gets longer. It's 22 longer than 22 pages. On Page 26 it says, "Still 23 suicide attempts, the total rate of suicides and 24 suicide attempts under Prozac amounts to 9.6 per 25 thousand," right, 0/00? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1954 1 A. Presumably, yeah. 2 Q. "Out of 1,362 patients treated with Prozac, one 3 committed suicide and twelve attempted suicide. Among 4 the other active drugs, namely, Imipramine, 5 Amitriptyline, and Doxepin, one suicide occurred in 6 598 patients. This would correspond to an incidence 7 rate." That incidence rate is another term that 8 epidemiologists use like odds ratio, right? 9 A. It was a term, yes. 10 Q. It takes somebody that's really schooled in 11 epidemiology to know the difference between those two, 12 right? 13 A. Wouldn't hurt. 14 Q. "The incidence rate under Prozac, therefore, 15 purely mathematically, is 5.6 times higher than other 16 active medications, Imipramine, Amitriptyline, and 17 Doxepin." So the date of this, if we'll turn back, 18 Ms. Barth, is May 21, 1985. The man has nearly two 19 months to factor in the patient years and do baseball 20 analogies and all that kind of stuff, and he's still 21 saying 5.6 times higher, true? 22 A. No. I think you've gone back to the point we 23 made yesterday, which is it's not credible to stop 24 prematurely. That number you're citing or pulling out 25 was where he was at in his preliminary, which was only PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1955 1 to our analogy, which was home runs per game. That 2 does not show us the number of events over the number 3 of patient days. So you're stopping prematurely and 4 making a conclusion. 5 Q. No, sir, I'm not. I'm saying that this man 6 did. This opinion leader that was hired by Lilly did. 7 A. I don't believe that, in his concluding 8 remarks, that he said anything about a higher risk of 9 Prozac relative to other agents. 10 Q. We'll look at his conclusion remarks. Back on 11 Page 29. He gets to the benefit/risk considerations. 12 "Concerning the benefit and risk of fluoxetine, the 13 following conclusions can be made in summary," and he 14 talks about efficacy. And then on Page 32 he says, 15 "In view of the benefit, as well as the risk, the 16 following claim of indications seems to be 17 appropriate." Indications is your verbiage or your 18 word for when somebody should take the pill, right, 19 when it's indicated that this pill should be 20 prescribed for a patient? 21 A. Type of clinical diagnosis where the medication 22 is being approved to be used. 23 Q. Okay. "Treatment of the depressive syndrome of 24 mainly endogenous genesis," now that's two big 25 mouthfuls of words to say. The origin genesis comes PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1956 1 from endogenous sources, which you just explained to 2 us, is from people that don't have any life stressor, 3 they just suddenly are depressed, right? 4 A. I'm sorry if I said that. Their depression 5 appears to come -- it doesn't mean that they don't 6 have life stressors. It would appear that the 7 depression has come on unrelated or minimally related 8 to those life stressors. At that point it was felt to 9 be more of a biologically-based depression. 10 Q. Okay, sir. And then finally he says on the 11 final page, "To take the potential risk into account, 12 the following addition appears to be appropriate: In 13 certain patients with severe depression, permanent 14 observation and/or sedative concomitant therapy might 15 be necessary." Now, what he's talking about there is 16 the warnings that would be given physicians, correct, 17 sir? 18 A. I don't know that it would be a warning. It 19 would be information contained in labeling. That is 20 very standard labeling for other antidepressants in 21 Germany, so that would not be surprising that that 22 would be a class concern. I think we've talked about 23 suicide in depression is a significant risk that needs 24 careful observation, and that is a class approach. As 25 it is in the U.S., it is in Germany. That was a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1957 1 standard sponsor or standard language. 2 Q. Does your company blame Dr. Randolph Neal for 3 prematurely releasing Bill Forsyth from Castle Medical 4 Center? 5 MR. SEE: Your Honor, I'm going to object. It 6 is beyond the scope of direct. I don't think 7 Dr. Tollefson has testified about the facts of this 8 case at all. 9 THE COURT: I'll sustain the objection. 10 MR. VICKERY: May I have a second to confer 11 with Ms. Barth? 12 (Whereupon, Mr. Vickery is conferring with 13 Ms. Barth.) 14 Q (By Mr. Vickery) I have a few questions from 15 yesterday and one additional matter to ask you about 16 and we're done. 17 Yesterday you said that you don't think that 18 the ACNP, the American College of 19 Neuropsychopharmacologists, would have any different 20 view than they did in 1992, correct, sir? 21 A. Collectively as a group, yes. 22 Q. And just so we'll all know, tell us who's the 23 president of the ACNP today? 24 A. Today, Dr. Steven Paul. 25 Q. Dr. Steven Paul who's higher up the food chain PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1958 1 at Lilly than you, right? 2 A. Equal. 3 Q. Equal, okay. So is it surprising to you with 4 him being the president of the ACNP that they wouldn't 5 change their mind today? 6 A. Dr. Paul just came into office. Dr. Paul was 7 not the president of the ACNP over the last five to 8 six years, so they've had numerous opportunities, but 9 let me just say, Dr. Steven Paul is an internationally 10 recognized scientist, and the ACNP would look at him 11 as a distinguished scientist, and his serving as 12 president of the ACNP reflects the fact that he is one 13 of the world's experts in psychopharmacology. 14 Q. I'm sure he appreciates those words. 15 A. He's earned them. 16 Q. Okay. A couple of other things. Yesterday you 17 mentioned this early period of time and I want to show 18 it to you, this early period of time in the 19 development of the drug -- 20 THE COURT: What exhibit are you on? 21 MR. VICKERY: This one doesn't have an exhibit 22 number. 23 MS. MANGRUM: It's on the back. 24 MR. VICKERY: It's on the back, okay. 25 Defendant's Exhibit 1077, Your Honor. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1959 1 Q. The early period of time, when -- before the 2 IND is even filed, before you even give it to humans, 3 when you're experimenting and doing toxicology studies 4 with animals, right, and we already know from looking 5 at your article that the whole issue of suicidality is 6 viewed by you as a toxicology issue or a drug toxicity 7 issue, right? 8 A. I don't think so, but you'd have to define it 9 for me. Usually when you think of toxicity, you're 10 thinking of too much, like very high levels in an 11 overdose. I don't think I ever equated it with toxic 12 concentrations. 13 Q. Would you like me to show you the article? 14 A. Yeah. If I called it toxicologic, sure. 15 Q. It was under -- in your article, it was under 16 drug toxicity. 17 A. I think I recall it from yesterday. 18 Q. You remember now saying -- 19 A. It is under a heading of things, that's 20 correct. 21 Q. Okay. Now, are the -- when you were giving it 22 to animals, dogs and cats, did their behavior become 23 more aggressive? 24 A. Yeah -- 25 MR. SEE: Your Honor, I object subject to the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1960 1 Court's prior ruling on these subjects. 2 THE COURT: Sustained. 3 Q (By Mr. Vickery) You mentioned therapeutic 4 doses of Pamelor. What is a therapeutic dose? 5 A. Of Pamelor? 6 Q. Yes, sir. 7 A. There isn't a single dose. There's a dose 8 range. Frequently it might be from 50 milligrams to 9 200 milligrams. Sometimes people will prefer to 10 actually measure the concentration of the drug in the 11 bloodstream and try to equate that with a more 12 therapeutic level of the drug as opposed to just the 13 dose, but the problem with the older tricyclics, 14 there's a wide range that might be necessary to 15 employ. 16 Q. I think we heard some other testimony that 100 17 milligrams was sort of generally thought to be the 18 therapeutic dose or the minimum therapeutic dose. Do 19 you agree with that? 20 A. Not the minimum therapeutic dose. It is within 21 a standard range that that drug would be used to treat 22 depression. I would agree with that. 23 Q. Okay, sir. Finally, I want to ask you, have -- 24 you know, we talked at some length about whether it's 25 fair to blame depression, the underlying disease. And PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1961 1 my question to you is, isn't it true that from the 2 very earliest time, from like 1990, as a matter of 3 public relations, a matter of marketing strategies, 4 your company has said, let's blame this problem on the 5 underlying disease? Isn't that true, sir? 6 A. No. 7 Q. All right. We're going to look at an exhibit 8 that involves your -- this gentleman, Dr. Thompson, 9 you talked about. 10 MR. VICKERY: Before we put this up there, 11 Judge, this is another one in the category that was 12 admitted for cross-examination purposes only. It's 13 Exhibit No. 123. I would like to cross-examine this 14 man about it. 15 MR. SEE: Your Honor, may we approach side bar? 16 THE COURT: All right. 17 (Whereupon, the following proceedings were had 18 at side bar out of the hearing of the jury.) 19 MR. SEE: We have a document here, Your Honor, 20 and our notes clearly reflect that the Court ruled 21 that the document was not to be admitted, but could be 22 used to cross-examine Dr. Thompson, if Dr. Thompson 23 was going to be a witness. The document talks about 24 Dr. Thompson and whether Dr. Thompson had media 25 training and so on. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1962 1 THE COURT: Dr. Thompson? 2 MR. SEE: It talks about whether Dr. Thompson 3 had media training. That's what Mr. Vickery wants to 4 talk about. 5 THE COURT: Mr. Vickery. 6 MR. VICKERY: Your Honor, I don't recall the 7 Court saying it was limited to cross-examining 8 Dr. Thompson. I think you said you can cross-examine. 9 This is not going to the jury, but you can 10 cross-examine on this document. We're in a situation 11 where here is the PR people at Lilly saying, hey, 12 cease control. Don't pay attention to what the papers 13 are saying and appear compassionate, and that's what 14 was said to Dr. Thompson with his media appearance. I 15 think for them to say to the Court, you only said they 16 can cross-examine Dr. Thompson and guess what, we're 17 not going to bring him even though he's on our witness 18 list, they deprived me of a very effective tool of 19 this man who has done exactly the things that 20 Dr. Thompson was advised and cautioned in this to do. 21 MR. SEE: The memo may, and I say may, say that 22 and if Dr. Thompson has been prepped to talk to the 23 media, if Dr. Thompson has message points to be 24 prepped to talk about, that goes to the credibility of 25 Dr. Thompson. It doesn't impeach this witness at all, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1963 1 and doesn't have anything to do with this witness. It 2 was eight years ago and it was only about 3 Dr. Thompson. 4 MR. VICKERY: In my view -- 5 THE COURT: I'll overrule and allow it for 6 cross-examination purposes. You may use it for 7 statements for impeachment. 8 (Whereupon, the following proceedings were had 9 in open court in the presence of the jury.) 10 Q (By Mr. Vickery) This is dated April 15, 1991 11 to Dr. Thompson, CC Ed West. And Ed West is the top 12 public relations guy for Lilly, isn't he? 13 A. Corporate communications. 14 Q. Is that the same thing? He speaks for Lilly to 15 the press and the media? 16 A. Yes, that's correct. 17 Q. Regarding upcoming TV appearances. "Thanks for 18 taking time for Friday practice session. Frankly, I 19 was unimpressed with the performance of our outside 20 professionals, and the greatest value in the morning 21 may prove to represent an improvement that Ed and I 22 will want to mandate in their future training 23 sessions, but a little practice in message honing is 24 usually useful even for a seasoned media pro like you. 25 "I took the liberty of jotting down the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1964 1 following notes from our morning's work, which I offer 2 to augment your own thoughts. Number one, message 3 goals. Whatever questions you are asked or direction 4 the interviews take, the three points we want to 5 establish are, number one, no medicine has ever been 6 more thoroughly researched." Now, that's a point 7 you've tried to make time and again here, haven't you? 8 A. Yes, sir. 9 Q. "Number two, it's in the disease, not the 10 drug." That's a point you've tried to make time and 11 again, haven't you? 12 A. Yes. 13 Q. "Number three, tragedy. People who are being 14 helped are being scared away." That's exactly the 15 same thing you said yesterday when I asked you about 16 the medical-legal implications. Remember when you 17 were criticizing Dr. Healy -- I'm sorry, Dr. Teicher, 18 remember that? 19 A. I do. 20 Q. So these three points are three points that you 21 have tried to make time and again in your testimony, 22 have you not, sir? 23 A. I have mentioned them. I believe that they're 24 all very valid. 25 Q. I want to know, were you instructed or coached PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1965 1 to try to make those points whatever the questions 2 were asked, regardless of what questions I asked? 3 A. Absolutely not. 4 Q. Okay. "Tone: We hope that the overall 5 impression left by your demeanor and word choice will 6 be that of a caring physician, personifying qualities 7 like compassion. You must constantly place yourself, 8 and therefore, Lilly, on the patient's side. Words 9 like tragic, heartening, and vulnerable will be 10 useful," and they go on talking about somebody else is 11 going to be on the attack. 12 "Number two, medical authority: Statistics and 13 factual reference lines like, as a physician back in 14 medical school, all help." You've used those kinds of 15 phrases here, haven't you? As a physician, 16 Dr. Thompson would be interested in this or I would be 17 interested in this. That's the very thing you've done 18 here, haven't you? 19 A. It's appropriate that we reflect the 20 credentials of the people we're talking about. If 21 it's a physician, I probably would refer to him as a 22 physician. 23 Q. And then, of course, friendliness, that says to 24 Dr. Thompson, "It just comes naturally." You've 25 tried, of course, to be friendly in your appearance PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1966 1 here, haven't you? You've tried to smile and be nice? 2 A. I tried to be very honest with you and be 3 myself. 4 Q. Were you coached or advised by the public 5 relations people to take a tone of compassion, medical 6 authority, and friendliness? 7 A. No. 8 Q. "Specific questions." Look at this one. "We 9 discussed handling the most critical questions." 10 A. Can I ask where you are? I'm sorry, I lost 11 you. 12 Q. I'm under number three, under specific 13 questions, getting ideas of how to answer specific 14 questions. "Isn't it conceivable, just barely 15 possible, that Prozac causes a few people to commit 16 violent or suicidal acts?" That's the question, 17 "Answer: Prozac is a safe drug. It works for 18 millions, but some it doesn't for and those people, 19 because of their disease, remain prone to tragic 20 behavior. If pressed or as a post-script of the 21 above, then make the point that absolutely no evidence 22 indicates Prozac is the cause of such behavior." 23 That's exactly what you've tried to do when 24 I've asked you about those very minor few people you 25 wrote about in 1991, is you've said, oh, it's a safe PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1967 1 drug. It works for millions. It's used all over the 2 world and depressed people are just at risk for 3 suicide. Isn't that exactly the tact you've taken 4 here? 5 MR. SEE: Object to the form, Your Honor. It 6 is argumentative. 7 THE COURT: Sustained. 8 Q (By Mr. Vickery) Were you -- never mind, I 9 won't ask that. 10 Well, another specific question, "What about 11 the adverse drug reports? The number of rashes, Lilly 12 standards, three and a half million patients. The 13 vast majority were things like rashes and nausea. As 14 a follow-up answer or as a post-script, get into 15 Lilly's high-reporting level across all drug 16 categories." 17 What Dr. Thompson was being told then is what 18 we saw in that memo of November of '90, is if you 19 would just put the numbers of suicide side by side 20 with vomit, it makes it look small, doesn't it? 21 A. I don't think so. 22 Q. Okay. What do you believe happened to Bill 23 Forsyth, Sr.? 24 MR. SEE: Object. It's beyond the scope. 25 Dr. Tollefson has not been asked to give testimony PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1968 1 regarding the specific facts of this case. 2 THE COURT: Sustained. 3 MR. VICKERY: I'll pass the witness. 4 CROSS-EXAMINATION 5 BY MR. SEE: 6 Q. Dr. Tollefson, do you have that 123 in front of 7 you there or not? The one that Mr. Vickery just 8 talked about, this public relations thing. 9 A. Yes, sir. 10 Q. Let's answer questions about it right now. 11 Exhibit 123 is a paper that was prepared about eight 12 years ago by a public relations person, wasn't it? 13 A. Yes. 14 Q. Now, I want you to go on the first page where 15 Mr. Vickery was asking about it. Did you see the 16 number one there under message goals? 17 A. Yes. 18 Q. I want to ask you about it. It says, "No 19 medicine for a brain disease has ever been more 20 thoroughly researched." Here's the question: Is that 21 true? 22 A. To the best of my knowledge, yes. We have over 23 11,000 papers on Prozac in the literature. 24 Q. Go down to number two. It says, "It's the 25 disease, not the drug. With Prozac, about two-thirds PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1969 1 of patients improve, the others do not." First, is 2 that true? 3 A. Yes. 4 Q. Is it correct that Prozac is, in that respect, 5 similar to the other antidepressant drugs, in that 6 about two-thirds of the people get relief for their 7 depressions, but unfortunately, another third does not 8 respond to the medicine? 9 A. That is correct. 10 Q. I'll go on. "Those that don't, remain 11 vulnerable to the tragic behaviors associated with low 12 serotonin levels." Here's the question, is that true? 13 A. Yes. I think our current belief is that 14 patients with protracted severe depression likely have 15 a high risk of having low levels of serotonin. 16 Q. So unfortunately, those patients who do not 17 respond to antidepressant medications, remain 18 vulnerable to the tragic behaviors associated with low 19 serotonin levels, right? 20 A. I think a large number of those patients who 21 have failed to respond may well be predisposed to that 22 low serotonin, you're correct. 23 Q. Now, go down to three. This PR piece that 24 Mr. Vickery read says, "Tragically, people who could 25 be helped are being scared away from people and that's PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1970 1 the public menace." Is that true? 2 A. Yes. 3 Q. Mr. Vickery asked you some questions about 4 Exhibit 17. No, I take that back. Mr. Vickery asked 5 you some questions -- I don't think you have it up 6 there, Doctor. Mr. Vickery asked you some questions 7 about several memos that went out to Lilly sales reps. 8 Do you recall that? 9 A. Yes. 10 Q. And the dates of those were January and 11 February and so on of 1990? 12 A. That's correct. 13 Q. And the tenor of those were, well, this Teicher 14 paper has come out and we want you to know about it. 15 You shouldn't bring it up yourself, but if doctors 16 have questions, get them back in touch with our 17 medical people, correct? 18 A. That's correct. 19 Q. And I think you gave testimony that the sales 20 reps were told not to bring that up because they had 21 not yet been instructed and trained on the 22 significance of that event, so that they, as 23 non-physicians, would be able to talk about it 24 appropriately, right? 25 A. In both the significance and complexity. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1971 1 MR. SEE: If I may approach the witness, Your 2 Honor? 3 THE COURT: You may. 4 Q (By Mr. See) Let me hand you Exhibit 17. 5 A. Thank you. 6 Q. Is that also a memo to Lilly sales 7 representatives? 8 A. Yes, sir. 9 Q. And what's the date on that? 10 A. August 3, 1990. 11 Q. And this memo to Lilly sales representatives 12 also tells them about an event, but it tells them also 13 not to bring it up themselves, right? 14 A. Yes. 15 Q. Now, go down to the place where it says, "You 16 should also be aware." 17 A. Okay. I have it. 18 Q. Would you read that out loud to the jury? 19 A. "You should also be aware that the Food and 20 Drug Administration has issued a statement that 21 discusses the February 1990 American Journal of 22 Psychiatry article and Prozac. The statement includes 23 the following observations," and it's a quote, "To 24 date, reviews of the available databases have failed 25 to identify similar cases," in parentheses, "to the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1972 1 ones reported in the American Journal of Psychiatry," 2 end of parentheses, end quote. 3 There's a second quote. "Prozac's labeling 4 from the time of approval has warned of the general 5 risk of suicide in depressed patients and recommended 6 close supervision of high-risk patients," end of 7 quote. 8 And then there's a third quote from the FDA. 9 "On the evidence currently available, there appears to 10 be no basis to conclude that the use of Prozac is 11 associated with any unreasonable or unexpected risk. 12 However, Prozac, like all potent drugs, should only be 13 prescribed as medically indicated under the 14 precautions recommended in Prozac's current labeling," 15 end of quote. 16 Q. Now, that event that the sales reps are being 17 advised about could be taken as a very positive 18 statement for Prozac; isn't that right? 19 A. Absolutely. I think it was a very positive 20 statement on the part of the Food and Drug 21 Administration. 22 Q. Yet, in the memo down at the bottom, what does 23 Lilly tell its sales reps to do? 24 A. It advises them not to initiate the discussion 25 on those items or, in particular, to use this letter PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1973 1 as a detailing effort to try to sell Prozac. 2 Q. Mr. Vickery asked you questions about your 3 article on the absence of a relationship between 4 adverse events and suicidality during pharmacotherapy 5 for depression, do you recall that? 6 A. Yes, sir. 7 Q. And then he referred you to several of the 8 references that you cited in the back? 9 A. Yes. 10 Q. And then they were the Damluji article and the 11 Teicher article and the Masand article and the King 12 article and so on. 13 A. That's correct. 14 Q. Do you recall that? Do you know from memory 15 the dates of all of those articles? 16 A. I probably wouldn't be 100 percent accurate, 17 but I know approximately. 18 Q. Let me just hand you, if I may, Your Honor. 19 Would you read the jury the dates of those case 20 reports that you cited in your article? 21 A. 1988, 1990, 1990, 1990, 1991, 1991, 1991, 1991. 22 Q. All right, sir. Now, let me ask you this: 23 Mr. Vickery wrote up on the pad there a couple of 24 quotes where you talked about there may possibly be 25 this effect, right, and the date of that was when? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1974 1 A. 1991. 2 Q. And he wrote up another quote where you talked 3 about the potential of suicidal ideation, right? 4 A. That's correct. 5 Q. And when was that? 6 A. Also '91. 7 Q. Now, Dr. Tollefson, I don't want you to go back 8 and repeat all of the testimony that you gave 9 yesterday. I don't think anybody does, to tell you 10 the truth, but I do want you in a summary, brief form, 11 since these case reports were published that you cited 12 in 1988, in 1990, in 1991, and since the time these 13 quotes were written in 1991 -- let me just ask one 14 question before I ask that one. When you say, 15 "potential," when you say, "possibly" in the other 16 quote, are you raising a question? 17 A. Yes. 18 Q. Would you tell the jury then what's been done 19 by Lilly and others since 1988, 1990, 1991 to answer 20 the question whether there really is a causal 21 relationship between taking Prozac and suicide or 22 violent behavior. 23 A. Well, as we said yesterday, obviously, very 24 much, let me start with Lilly. Lilly has done 25 extensive meta-analysis. It has sponsored and been PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1975 1 involved with prospective large-scale epidemiological 2 studies. It has conducted, itself, prospective 3 clinical trials into depression and suicide. It has 4 also looked at special high-risk populations to try to 5 address the issue. 6 This has also been addressed in the academic 7 community by a number of institutions. We heard about 8 some of those yesterday, such as Brown University or 9 the National Institutes of Mental Health branch of the 10 federal government. Even our competitors have done 11 comparative studies prospectively against this 12 compound investigating this issue, and I believe, as 13 we said yesterday, all of those studies concluded the 14 same thing, that there is no credible scientific 15 evidence to support a causal association between any 16 antidepressant and suicidality. 17 Q. I'm taking my life in my hands by touching this 18 particular easel, but you have to do certain things in 19 this business. 20 Now, Mr. Vickery wrote down a date, 1985, and 21 he wrote next to it, "BGA rejects," and I'm going down 22 this list to see if he -- I think he may have left 23 something out, and there were lots of questions and 24 documents about the application by Lilly to have 25 Prozac approved for use in Germany. Now, what's the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1976 1 date that's not on Mr. Vickery's list about Germany? 2 A. Probably 1990. 3 Q. And what happened then? 4 A. It was approved by the BGA for marketing in 5 Germany as an antidepressant. 6 Q. And is it still approved there today? 7 A. Yes, sir. 8 Q. Mr. Vickery asked you about 88 reports of 9 homicide -- that's wrong, 88 reports of a death of 10 another person associated with somebody taking Prozac. 11 You recall that testimony? 12 A. Yes, I do. 13 Q. Were all of those events, those 88 events, a 14 person taking Prozac killing somebody else? 15 A. Absolutely not. 16 Q. Give us an example of one that's not. 17 A. Well, one could be, regrettably, if you're 18 driving down the highway and let's say your spouse is 19 in the car with you, and she happened to be treated 20 for depression and is receiving Prozac and you're 21 involved in an automobile accident and both you and 22 your spouse would die in that automobile accident, 23 that would count in that listing of 88 deaths 24 associated with individuals taking the medication. 25 Q. Now, let's put 88 deaths in context. First, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1977 1 what's the homicide rate in United States per 100,000 2 people? 3 A. I can give you an approximation. The Center 4 for Disease Control, I think, has numbers that 5 approach about 8-1/2 homicides per 100,000 in our 6 population in the U.S. 7 Q. 8.5 per 100,000 people, right? 8 A. Annually, I believe. 9 Q. How many people are taking Prozac in the United 10 States, Doctor? 11 A. Our exposure for Prozac now is in excess of 12 38 million patients. 13 Q. That's in the United States? 14 A. That would be globally, although 15 conservatively, I would say 70 percent would be in the 16 U.S. 17 Q. Okay. Let me go back to clarify because I may 18 have said something wrong. These 88 reports of 19 deaths, was that globally? 20 A. They should be, yes. 21 Q. Mr. Vickery asked you some questions about two 22 physicians from Taiwan, Drs. Lu and Ko? 23 A. Yes. 24 Q. And you testified that Drs. Lu and Ko came to 25 Lilly and asked for advice about the fact that they PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1978 1 wanted to get a publication in a major journal in the 2 United States? 3 A. Yes. 4 Q. And they presented some information to you and 5 to Lilly about some work that they had done before 6 they came; is that right? 7 A. That's correct. 8 Q. Dr. Tollefson, what I want to have you tell the 9 jury is when you got -- you and Lilly, when you got 10 that information from Drs. Lu and Ko, did you report 11 it to the Food and Drug Administration? 12 A. We did very promptly after that meeting. 13 Q. Did you hide anything about it, Doctor? 14 A. We fully reported all that material to the Food 15 and Drug Administration. 16 Q. Now, Mr. Vickery has also asked you some 17 questions about this meta-analysis about Prozac 18 controlled clinical trials that was conducted by 19 Dr. Beasley, right? 20 A. Yes. 21 Q. And in discussing the DEN, the Drug 22 Epidemiology Network, that Lilly computer database, I 23 think he made a suggestion using the phrase garbage 24 in, garbage out that maybe not all of the suicidal 25 acts or events would be in the DEN database, and it is PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1979 1 to that issue that I'd like to ask you a question. If 2 I may, Your Honor, let me hand you a copy of 3 Dr. Beasley's meta-analysis. If you'd turn over to 4 the method's section, which is on the second page? 5 A. Um-hum. 6 Q. Have you recently had a chance to look at this, 7 by the way? 8 A. Yes. 9 Q. Now, tell the jury whether the only source of 10 looking for adverse events from the controlled 11 clinical trials used by Dr. Beasley was the DEN or DEN 12 database? 13 A. It was not the only source used. 14 Q. Okay. Tell us what else Dr. Beasley and his 15 colleagues did. 16 A. Well, Dr. Beasley and his colleagues, in the 17 method section of the paper where they described what 18 they did in order to get the data, essentially, 19 identified two sources of information, one is an 20 electronic scan of what's called the clinical report 21 form data. That, again, is the form that the doctor 22 uses at his site to write about the patient, how well 23 they're doing if they're not doing well. 24 Q. Clinical report form, if I could interrupt you 25 so we all understand what that is. The clinical PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1980 1 report form is not some bit of information contained 2 in a computer. It is the actual form that the doctor, 3 the investigator, in the study fills out at the study 4 site? 5 A. That's correct, sometimes referred to as the 6 source document because it is right there. It's what 7 the doctor has, what he or she might write on. 8 Q. So in gathering information for this 9 meta-analysis, Dr. Beasley and his colleagues went 10 back to the original source document to gather those 11 events? 12 A. That's correct. 13 MR. VICKERY: Excuse me, Mr. See. I object to 14 counsel leading this witness. 15 THE COURT: Sustained. 16 Q (By Mr. See) Now, Mr. Vickery asked you about 17 a memo from a Mr. Bouchy in Germany. Do you recall 18 that? 19 A. Yes, sir. 20 Q. And in that memo, Mr. Bouchy was asking 21 questions and expressing admittedly some concern that 22 he felt about this coding system for adverse events; 23 isn't that right? 24 A. I believe so. 25 Q. Now, would you tell the jury, when an adverse PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1981 1 event is reported to Lilly, what does Lilly then send 2 on to the FDA? 3 A. Typically, it would send four or five pages of 4 information that would include, at least, three 5 things; number one, whatever the term was that the 6 doctor chose to use for the event, number two would be 7 a textual description of what the doctor said about 8 the event, and thirdly would be for the FDA's 9 classification purposes, what category that event 10 would fall under or where we say maps to. 11 Q. That's the code term? 12 A. That's a Code Start term, that's correct. 13 Q. So that coding term, that was the term that 14 Mr. Bouchy was concerned about? 15 A. That is correct. 16 Q. But you said that coding term and then the 17 exact term that the doctor uses and then also a 18 description -- 19 A. Right. 20 Q. -- all three? 21 A. Yes, sir. 22 Q. By using the coding terms as one of the three 23 ways you send information to the FDA, does that hide 24 anything? 25 A. No. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1982 1 Q. Now, also Mr. Vickery has asked you some 2 questions, again, about these memos to Lilly sales 3 representatives following the Teicher article and 4 emphasized that they were instructed that they ought 5 not raise this themselves, you remember that? 6 A. Yes, sir. 7 MR. SEE: If I may, again, approach the 8 witness, Your Honor? 9 Q. Let me hand you Exhibit 1042, and although we 10 looked at it and identified it and admitted it into 11 evidence yesterday, you didn't go into any detail 12 about it and now I think we should. Would you open up 13 to the first page? 14 A. Yes. 15 Q. First, this is the Dear Doctor letter that 16 Lilly on August 31, 1990 sent to every physician in 17 the United States? 18 A. Yes, it is. 19 Q. Would you, on the first page there, in the Dear 20 Doctor letter, would you read -- it's very long, but 21 let's read some of it. Would you read to the jury the 22 second paragraph? 23 THE COURT: Excuse me. Before we get started 24 on this, let's take a break and please be back at ten 25 to three. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1983 1 (Whereupon, a recess was taken from 2:35 p.m. 2 to 3:05 p.m.) 3 THE COURT: Please proceed, Mr. See. 4 MR. SEE: Thank you, Your Honor. 5 Q. Dr. Tollefson, you have in front of you the 6 Dear Doctor letter that's been marked as Exhibit 1042 7 dated August 31, 1990. Just to remind us all, this is 8 a letter that Lilly sent to every doctor in the United 9 States? 10 A. Yes, sir. 11 Q. Would you read the second paragraph to the 12 jury, please? 13 A. "In recent months, a number of articles and 14 programs concerning the possible relationship between 15 therapy with Prozac and suicidal ideation have 16 appeared in the lay media. This possibility was 17 raised in a retrospective review of six clinical cases 18 of patients with refractory or chronic depression and 19 complicated psychiatric histories which appeared as an 20 article in the February 1990 issue of the American 21 Journal of Psychiatry." 22 Q. Would you read the next paragraph? 23 A. "Based on ongoing analyses of clinical trial 24 data and information currently available, the data 25 taken as a whole do not support the scientific PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1984 1 hypothesis of a causal relationship between Prozac and 2 suicidality," then in parentheses, "ideation or acts." 3 Q. And then, finally, would you read the next 4 paragraph? 5 A. "When using any antidepressant therapy, 6 clinicians must remain vigilant for direct or indirect 7 communication of suicidality, including emergence of 8 or changes in intensity of suicidal thoughts in order 9 to take appropriate clinical action." 10 Q. And attached to the Dear Doctor letter at that 11 time was there a copy of the entire prescribing 12 information for physicians from Lilly? 13 A. Yes, sir. 14 Q. Dr. Tollefson, I want to refer back to 15 Dr. Beasley's meta-analysis just to make sure we all 16 understand. First, you had referred to his methods 17 section, if you can recall? 18 A. Yes, sir. 19 Q. And one of the referrals was that there was an 20 electronic search of the clinical report form data, do 21 you recall that? 22 A. Yes. 23 Q. And what I'd like to ask is this: Does Lilly 24 have the capacity to search for specific terms, and 25 any terms that were used, by computer? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1985 1 A. Yes. 2 Q. So if you want to find, in the clinical trial 3 database, any specific term used by a doctor or 4 investigator to describe a particular event that was 5 observed, you have a computer capacity to do that? 6 A. Yes. 7 Q. I asked you before about these case reports 8 that had been referred to by Mr. Vickery and you read 9 some of the dates off as being in 1990 and 1991 and so 10 on. Do you recall that? 11 A. Yes. 12 Q. What I want to ask you now is, after Lilly made 13 its submission of data to the FDA about this issue and 14 after the FDA's conclusions and after the publications 15 of the epidemiology studies that you read some from 16 yesterday, do you still see a flurry of case reports 17 in the medical literature about Prozac being observed 18 or about suicidality being observed with Prozac? 19 A. I'm not aware of any over the last several 20 years. 21 Q. Mr. Vickery also asked you about the memo 22 written to Dr. Leigh Thompson from Dr. Bouchy, and 23 then you said there was a response by Dr. Thompson and 24 then he didn't read any of that and then he read 25 Dr. Bouchy's memo back. What I would like to do is PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1986 1 hand you Exhibit 1124 which is, in fact, 2 Dr. Thompson's response to Mr. Bouchy, and just ask 3 you to read that first paragraph marked there to the 4 jury. 5 A. "This is such a good and important point that 6 I'm hereby asking that Bob Zerbe and Allan Weinstein 7 organize an appropriate group to discuss it. I would 8 like very much to emphasize again that we never," in 9 capital letters here, "that we never diminish 10 information content in a report by deleting any words 11 of the reporter. Never ever. The Code Start 12 classification terms which were invented by and 13 maintained by the FDA, and now required for electronic 14 reporting of adverse events to the FDA," in 15 parentheses, "are just classification terms. They are 16 just pigeon holes in which to file reports so they can 17 retrieve all the ones of a certain type." 18 Q. All right. Thank you. Now, the last thing I 19 want to ask you about is, Mr. Vickery asked you 20 several questions about warnings that should go in 21 package inserts, do you remember that? 22 A. Yes. 23 Q. And he mentioned during those questioning, 24 warnings with a box around them and that sort of 25 thing, do you recall that? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1987 1 A. Yes, I do. 2 Q. In fact, the Food and Drug Administration has 3 been asked to and, in fact, made a conclusion with 4 respect to that kind of warning in Prozac, hasn't it? 5 A. Yes, it has. 6 Q. Let me hand you Exhibit 1049. And my question 7 for you is, is this the response by the Food and Drug 8 Administration to a request that the warning for 9 Prozac have -- or the insert for Prozac have a 10 different warning on it? 11 A. Yes. 12 Q. And the date is what, please? 13 A. June 3, 1992. 14 Q. Okay. Would you just read the first two 15 paragraphs? 16 MR. SEE: Before you do that, Your Honor, may I 17 offer 1049? 18 MR. VICKERY: No objection. 19 THE COURT: 1049 is in evidence. 20 (Whereupon, Defendant's Exhibit 1049 is 21 admitted.) 22 Q (By Mr. See) Would you just read the first 23 two paragraphs to the jury? 24 A. "This responds to your citizen petition dated 25 May 23, 1991, requesting that the Food and Drug PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1988 1 Administration immediately revise the approved 2 labeling of the antidepressant Prozac or fluoxetine 3 manufactured by Eli Lilly and Company, Lilly, to 4 include a boxed warning regarding its association with 5 intense, violent, suicidal preoccupation, agitation, 6 and impulsivity in a small minority of patients. 7 "We have reviewed your citizen petition and 8 have evaluated all currently available relevant 9 evidence. Because this evidence is not sufficient to 10 reasonably conclude that the use of Prozac is possibly 11 associated with suicidal ideation and behavior," 12 parentheses, "suicidality, we are denying your 13 request. However, we will continue to carefully 14 examine any information that might suggest a potential 15 relationship." 16 MR. SEE: Thank you, Dr. Tollefson. I pass the 17 witness. 18 THE COURT: Mr. Vickery. 19 MR. VICKERY: Just a few things. 20 REDIRECT EXAMINATION 21 BY MR. VICKERY: 22 Q. Doctor, now, when that citizen asked the FDA to 23 do that, that's just one citizen somewhere, right? 24 That's the way that works? 25 A. Yes. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1989 1 Q. And that citizen doesn't have the ability, as 2 we do here, to compel Lilly to come forward and to 3 cross-examine you guys and put you under oath and all 4 that stuff, do they? 5 A. No. 6 Q. How did Eli Lilly respond when the citizen 7 said, hey, give more specific warnings on this, make 8 them do that FDA? How did your company respond? 9 A. I think the request was made to the Food and 10 Drug Administration. The company provided the Food 11 and Drug Administration all available information that 12 the company had and then the FDA rendered their 13 opinion. 14 Q. Did the company say, here's the information, 15 you tell us what to do? Or did the company say, we 16 don't want to do it, we don't think we need to do it? 17 A. I'm not aware of the latter. I'm sure that the 18 company's position, based on the scientific data, is 19 that we don't see evidence of a reasonable 20 association, but that was the FDA's decision to make. 21 Q. Why would that be the company's position? I 22 mean, why would Lilly not just do it, just put this 23 language in there? What would it hurt to do it? 24 MR. SEE: Objection to the form, argumentative. 25 THE COURT: Sustained. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1990 1 Q (By Mr. Vickery) Would it harm anybody to 2 give physicians this additional information? 3 MR. SEE: Objection to the form, argumentative. 4 THE COURT: Same ruling. 5 Q (By Mr. Vickery) Can you tell us why the 6 company took the position it did? 7 A. Which position? 8 Q. The position that they shouldn't change the 9 warning. 10 A. The company did not believe that there was 11 scientific evidence to support a change. Package 12 labeling is based on scientific information when it 13 comes to the warning section. 14 Q. And the Dear Doctor letter that you've just 15 read from, that didn't say to the doctors, our drug 16 causes akathisia or causes violence or causes suicide 17 in a small minority of patients. It said exactly the 18 opposite, didn't it, our drug doesn't cause this? 19 MR. SEE: Objection to the form, argumentative. 20 MR. VICKERY: It's cross-examination, Your 21 Honor. 22 THE COURT: I'll allow the question. 23 THE WITNESS: I believe it included the package 24 insert that would have included all of the adverse 25 events observed during clinical trials, which would PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1991 1 have included those terms. 2 Q (By Mr. Vickery) That letter did exactly what 3 your August 3rd memo, which was Plaintiffs' 4 Exhibit 17, told the salespeople to do, which is to 5 simply reassure the doctors; isn't that true, 6 Dr. Tollefson? 7 A. I think it was an educational effort to allow 8 the doctors then to make their own judgments based on 9 the data. 10 Q. Now, Mr. See asked you about the information in 11 that letter to the detail people about what the FDA 12 had decided. Given that Lilly had a very high-place 13 defender in the FDA who thought this was garbage, who 14 had an arrangement to receive information, not through 15 regular channels, is it surprising to you that the FDA 16 would come out on your side on the issue? 17 MR. SEE: Object to the form. There's no 18 foundation. It's argumentative. 19 THE COURT: I'll sustain the objection as to 20 argumentative. 21 MR. VICKERY: The only additional thing I have, 22 Your Honor, is the short excerpt from the deposition 23 offered for impeachment purposes only. 24 THE COURT: All right. Let's meet at side bar. 25 (Whereupon, the following proceedings were had PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1992 1 at side bar out of the hearing of the jury.) 2 THE COURT: I understand what you are proposing 3 now is Page 278, Line 5 to Line 10. 4 MR. VICKERY: To Line 10 on Page 279, that's 5 right, Judge. 6 THE COURT: Did you see that? 7 MR. SEE: I've read it and it's not impeachment 8 of any testimony yet. It says exactly what he said, 9 except for one question and that's the last question, 10 and he gave no testimony about that. It's not 11 impeaching. 12 THE COURT: Well, I think it is very 13 questionable, except I do think that the statement 14 about surveying the question whether or not the FDA 15 expected such a study is a fair question that he can 16 ask. 17 MR. SEE: I don't think he gave any testimony 18 on it, so it's not impeaching. 19 THE COURT: Well, I think that he was cut off 20 by you at that point. So he can't ask any -- he 21 wanted to ask him about eight or ten pages I guess of 22 this deposition. 23 MR. VICKERY: I saw the handwriting on the wall 24 on that one, Your Honor, that's why I limited the 25 offer to the very small portion. I'd like to play PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1993 1 that on the video is what I'd like to do. 2 THE COURT: Video? 3 MR. VICKERY: I have a video deposition cued up 4 to play it of him saying it. It's better than me 5 reading it. 6 THE COURT: You can ask him about these 7 questions -- 8 MR. VICKERY: Okay. 9 THE COURT: -- about this deposition. 10 MR. VICKERY: All right. Your Honor, while 11 we're here, I don't want to say anything about this in 12 front of the jury, but this witness -- I do not want 13 this witness excused. I want him subject to recall 14 for phase two. 15 THE COURT: For the what? 16 MR. VICKERY: For punitive damages. I think 17 that's probably not necessary since he's already 18 within the jurisdiction of the Court, but I want to 19 make sure this man is told if he's going to leave 20 town, that he is subject to recall in this court for 21 phase two. 22 THE COURT: Do you have any problem with that, 23 Mr. See? 24 MR. SEE: I want the record to reflect under 25 Rule 45, a subpoena is not valid, but the witness is PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1994 1 here and is subject to the Court's direction. The 2 subpoena is not valid. 3 THE COURT: I direct him to be available. 4 (Whereupon, the following proceedings were had 5 in open court in the presence of the jury.) 6 Q (By Mr. Vickery) Dr. Tollefson, there's a 7 short passage from your prior deposition that I want 8 to go over with you. Do you have it there? 9 A. I believe so, sir. 10 Q. I think the most expedited way to do this maybe 11 is if I just ask the questions that you were asked and 12 if you'll just read the answers. 13 THE COURT: I just want you to ask him the 14 questions and see if he can answer them. 15 Q (By Mr. Vickery) All right. Was there ever a 16 formal decision made not to do the rechallenge study? 17 In other words, just to sort of drop it, the 18 rechallenge study that Dr. Beasley drafted? 19 A. We made a decision that it was not a reasonable 20 scientific method to go forward with, so we did not do 21 it. It was an active decision. 22 Q. And who made the decision? 23 A. A collective group within our medical team, 24 which included myself and a number of other 25 physicians. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1995 1 Q. Did anyone in the group vote not to do it, 2 think that you were obligated to do it? 3 A. No. We made that decision unanimously after 4 discussion about the pros and cons of each of the 5 different kinds of methods. 6 Q. Please read Page 279, your answer beginning at 7 line three to yourself and see if that refreshes your 8 recollection about that matter. 9 MR. SEE: It's not impeachment. 10 THE COURT: That's correct. That doesn't 11 contradict his statement. You better rephrase your 12 question. 13 MR. VICKERY: Okay. 14 Q. Well, did anyone vote to proceed with a 15 rechallenge study in that group? 16 A. Not that I recall. 17 Q. Now, did someone raise the question of whether 18 or not the FDA expected such a study? 19 A. Yes. 20 Q. Who was that? 21 A. Dr. Zerbe. 22 Q. And did anyone ever formally tell the FDA that, 23 hey, we're not going to do this study? 24 A. I think after the formal review by the FDA, it 25 was no longer an issue. I'm not aware of either the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1996 1 FDA corresponding to Lilly about the study or Lilly 2 ultimately sending a letter of formal correspondence 3 back to the FDA. 4 Q. You simply don't know one way or the other? 5 A. That's correct. 6 MR. VICKERY: All right. Very good. That's 7 all I have, sir. 8 MR. SEE: Nothing further, Your Honor. 9 THE COURT: Thank you. You may step down. 10 THE WITNESS: Thank you. 11 THE COURT: Well, are we on to your second 12 witness? 13 MR. SEE: We are, Your Honor, and we believe we 14 may be able to finish him today. 15 THE COURT: What's his name? 16 MR. SEE: Your Honor, Eli Lilly calls 17 Dr. Kenneth Tardiff. 18 THE CLERK: Please raise your right hand. 19 KENNETH TARDIFF, M.D., Ph.D., 20 called as a witness on behalf of the Defendant, after 21 having been first duly sworn to tell the truth, the 22 whole truth, and nothing but the truth, was examined 23 and testified as follows: 24 THE CLERK: Please be seated. Please state 25 your name and spell your last name. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1997 1 THE WITNESS: Kenneth Tardiff, T-A-R-D-I-F-F. 2 DIRECT EXAMINATION 3 BY MR. SEE: 4 Q. Good afternoon, Dr. Tardiff. 5 A. Good afternoon. 6 Q. Where do you live, sir? 7 A. I live in New York City. 8 Q. And you're a medical doctor? 9 A. Yes, I am. 10 Q. You're also a psychiatrist? 11 A. Yes, I am. 12 Q. Would you tell us first where you're originally 13 from and just detail your education for us, please. 14 A. Sure. I was born and raised in New Orleans, 15 Louisiana. I attended Tulane University Medical 16 School. Following that, I did an internship in New 17 York City at Saint Vincent's Hospital. I then went on 18 to do my psychiatric residency training at the 19 Massachusetts General Hospital, which is affiliated 20 with Harvard University in Boston. 21 Following my -- and at the same time I did my 22 residency, I also obtained a masters of public health 23 degree from the Harvard School of Public Health, and 24 there I specialized in epidemiology. 25 Q. You'll have to tell us what epidemiology is. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1998 1 A. Okay. Epidemiology is the study of epidemics, 2 although it's been enlarged to do other things. 3 Epidemiologists look at large numbers of events, be it 4 infectious disease, suicides, AIDS, or whatever. We 5 look at these large number of events and try to 6 determine how they are related to certain 7 characteristics; for example, age, gender, race, where 8 they take place, to look at environmental things that 9 may be causing a particular disease. And we use 10 statistics to determine whether the presence of 11 disease in a particular age group or geography is 12 statistically significant. 13 Epidemiology began a few decades ago in London 14 where there was an outbreak of cholera. In those 15 days, people didn't know what caused infectious 16 disease, so Lord Snow mapped cases of cholera in the 17 city of London and then theorized as to why they were 18 distributed there. To make a long story short, it was 19 due to the water supply, a part was contaminated and 20 part wasn't. 21 Today we also use epidemiology to study things 22 like AIDS. For example, early on we had no idea what 23 caused AIDS, and so through mapping cases of AIDS in 24 relation to exposure to blood, sexual activity, and 25 such, we were able to determine that it was probably PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1999 1 an infectious agent that caused AIDS, and of course 2 today, we're much more sophisticated. 3 Now, with suicides and homicides, I do the same 4 thing. Perhaps I don't know if I should go into that 5 right now, but I do the epidemiology of suicide and 6 homicide so as to determine factors that cause these 7 two phenomenon. 8 Q. What is your current position? 9 A. I'm currently professor of psychiatry and 10 public health at Cornell Medical College, the New York 11 Hospital. This is a hospital located on the upper 12 east side of Manhattan. It's a large place, a 13 distinguished place, and there I'm professor of 14 psychiatry and public health, and I do a number of 15 things as professor. 16 Q. First, let's ask what those are. Do you teach, 17 for example? 18 A. I teach residents. I teach medical students. 19 I give lectures around the country. 20 Q. On what subjects do you teach? 21 A. On violence and suicide. 22 Q. Do you perform research? 23 A. Yes. I'm funded -- I do research with the 24 medical examiner in New York City, so that I look at 25 all homicides, all suicides, and all accidents in New PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2000 1 York City. I've had a grant to study these from the 2 National Institute of Drug Abuse for the past ten 3 years, so I've had an opportunity to look at 14,000 4 homicides, roughly 8,000 suicides, and relevant to 5 this case, 128 murder/suicides. 6 Q. In your study of violence and suicide, have you 7 had professional publications? 8 A. Yes. I have over 150 publications in journal 9 articles, chapters in books, and a couple in several 10 books. Again, the prime focus of this writing is 11 violence and suicide. 12 Q. Have you written specifically on the 13 epidemiology of murder/suicide? 14 A. Yes. My colleague, Peter Marsick and I, along 15 with the medical examiner, reviewed case studies of 16 homicide/suicide and we wrote a paper which was 17 published in The Journal of the American Medical 18 Association in 1992. 19 Q. Have you received a particular award regarding 20 your writings in the area of studies of violence? 21 A. In 19, I think, '85 or whatever, I received an 22 award called the Manford Goodmocker Award which is -- 23 Q. Who gives that award? 24 A. -- which is given by The American Psychiatric 25 Association and The American Academy of Psychiatry in PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2001 1 the Law for the best publication for that year in the 2 area of legal psychiatry. 3 MR. SEE: Your Honor, at this time I would 4 tender Dr. Tardiff as an expert in the areas of 5 general psychiatry, of epidemiology, and of the study 6 of violence and suicide. 7 MR. VICKERY: Dr. Tardiff is clearly qualified 8 under Rule 702 to render opinion testimony, Your 9 Honor. 10 THE COURT: Thank you. The Court finds 11 Dr. Tardiff qualified as an expert in the area of 12 epidemiology, psychiatry -- did you say general 13 psychology or psychiatry? 14 MR. SEE: I said general psychiatry. If I 15 misspoke, I apologize. 16 THE COURT: General psychiatry in violence and 17 homicide. 18 Q (By Mr. See) Now, Dr. Tardiff, this case 19 concerns a specific kind of event -- 20 THE COURT: Excuse me, did you mean to say 21 violence and suicide? 22 MR. SEE: I did mean to say violence and 23 suicide, Your Honor. 24 Q (By Mr. See) Now, Dr. Tardiff, this case 25 concerns a specific event of homicide/suicide or is PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2002 1 that also termed murder/suicide sometimes? 2 A. It is really properly called homicide/suicide 3 because murder is more of a legal term, but it's been 4 studied so long and it's been referred to as 5 murder/suicide that we call it murder/suicide. 6 Q. Now, I want to ask you specifically, we're all 7 familiar, even especially from reading the newspapers, 8 that there are events of homicide or murder. Does the 9 epidemiology; that is, the patterns and facts 10 surrounding homicides resemble this event we have in 11 this case, a homicide/suicide? 12 A. No, it doesn't. Homicides usually involve men 13 killing other men, usually young men killing other 14 men, often related to drug dealing, poverty, and so 15 on. The phenomenon of murder/suicide is quite 16 different. I've studied it and it's, basically, very 17 rare, however, it's very commonly manifested the same 18 way, actually throughout the world, okay. So even 19 though countries may have variations in terms of rates 20 of homicide, the rate of murder/suicide is constant, 21 but low throughout the world. 22 Murder/suicide has been studied for four or 23 five decades. Even though it's very rare, it's 24 obviously a very serious dramatic thing, and so it's 25 received a lot of study. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2003 1 Q. First, from your study of homicide/suicide, are 2 there certain types or categories of those events? 3 A. Yes. I'm basing this testimony on my study, 4 but also a review of 20 or more studies that have been 5 done and they're pretty uniform in terms of what we 6 find. 7 Q. First let's go to the types or categories of 8 events. How many types of murder/suicides, how many 9 are there? 10 A. In about a half to three-fourths of the cases, 11 the murder/suicide involves a spouse or lover, okay. 12 That's a large number of cases. A spouse, a lover. 13 Of those cases, there are really three different 14 types. One is a husband killing a wife or lover 15 because he's jealous. He's accusing her of 16 infidelity. This is usually perpetrated by a young 17 man, although there are some older people, too, but by 18 and large, the age tends to be younger than the other 19 types of -- 20 Q. Let me just ask you a question about this first 21 type, the jealousy. You say this is by and large 22 younger males killing females? 23 A. Yes. 24 Q. And in this first subtype, the jealousy type, 25 is there generally a history of prior violence? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2004 1 A. Yes. There's often a history of spouse abuse 2 and so on. 3 Q. What's the second type? 4 A. The second type is an older man killing his 5 wife, and here we often have -- it's characterized by 6 failing health, either of the husband and/or the wife. 7 So in that sense it sort of resembles a mercy killing 8 kind of situation. 9 Q. In this mercy killing type of homicide/suicide, 10 is there generally a history of prior domestic 11 violence? 12 A. No. 13 Q. And what's the third type? 14 A. The third type also involves an older man who 15 kills his wife or lover. The man is 16 characteristically depressed. In this case there is 17 no history -- usually no history of spouse abuse. 18 Q. Let me first ask you, is there a label we can 19 put on those or something you call that particular 20 type? 21 A. Maybe depressed male. 22 Q. Now, is there by and large a history of prior 23 domestic violence in this third category, the 24 depressed male category? 25 A. Usually not. It can occur, but usually there PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2005 1 isn't. Certainly it is nowhere near the first type 2 where there is, you know, spouse abuse. 3 Q. Now, let me ask you specific questions about 4 the third type. The first thing I want to ask you 5 about is based upon your own studies and the other 6 studies in the literature that you have reviewed and 7 are familiar with, generally who carries out this kind 8 of an act? Who is the perpetrator as the police would 9 say? 10 A. Okay. It's an older man who is depressed, 11 oftentimes there are stresses on the family, be it 12 financial stress, marital stress, or other kinds of 13 social stress within the relationship. Oftentimes 14 it's a long -- a relationship of long duration. 15 Q. All right. First you said the perpetrator is 16 generally a male? 17 A. Yes. 18 Q. And the age? 19 A. Usually fifty or older. 20 Q. And do we know, based upon the studies that 21 have been done, about the socioeconomic level, the 22 income level of people that do this? 23 A. Usually they are middle class or upper class. 24 People that have jobs, that are successful, have been 25 successful. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2006 1 Q. And is there information from the studies, 2 generally, whether there is a psychiatric illness 3 present in this subtype of homicide/suicide? 4 A. The person is usually depressed. 5 Q. Now, what do we know about the victim? Who is 6 the victim? 7 A. The victim is the wife or lover. 8 Q. So the relationship -- okay. Usually the wife 9 or the lover of the victim, the gender base of the 10 victim is usually the female? 11 A. Definitely. We're talking about 90, 95 percent 12 of the cases. 13 Q. Now, I want to ask you, what do the studies 14 show about the circumstances of the relationship 15 between the male and the female? 16 A. Okay. Oftentimes there are issues within the 17 marriage. Oftentimes there is -- because the person 18 is depressed, there's a shift in terms of his role 19 within the relationship, so that it's described as -- 20 I think one article says, control versus dependency; 21 that is, the male is used to, in essence, controlling 22 things that happen within the family. Because of 23 depression or other things, he no longer has the 24 control that he did. Oftentimes there's marital 25 conflict, and then because he can't handle the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2007 1 situation by virtue of what he used to be, and he's 2 depressed, that he reacts in a rage killing the wife 3 and then himself. Oftentimes the main dynamics of 4 those of suicide, not homicide. 5 Q. When you say, "the main dynamic is suicide not 6 homicide," you'll have to explain for us what that 7 means. 8 A. Okay. It's based on the psychology of suicide, 9 where there's low self-esteem, hopelessness, there's 10 no way out. These are the characteristic 11 psychological dynamics of suicide. The person really 12 believes that there is no way to change what's going 13 on and because of that, he kills himself. 14 Q. Do the studies show us anything about the 15 location, where these acts take place? 16 A. There are several studies that have looked at 17 that. Characteristically it takes place in the home, 18 and in the home, the two places most likely to have a 19 murder/suicide is in the bedroom and in the living 20 room. Which makes sense because that's where they're 21 talking, that's where arguments can take place. 22 Q. Now, let me ask you with respect to, again, 23 this subclass, what about the history of domestic 24 violence? Tell us about whether, in a depressed male 25 type of homicide/suicide, you have a history of prior PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2008 1 domestic violence. 2 A. There usually is not a history of prior 3 domestic violence. There are verbal arguments, but 4 not a history of spouse abuse. 5 Q. Do you have your article, "The Epidemiology of 6 Murder/Suicide" there in front of you? 7 A. No, I don't. 8 Q. Let me draw to your attention this statement 9 from your article and we'll ask you to explain it to 10 the jury. 11 MR. VICKERY: Would you give me the page, 12 please? 13 MR. SEE: I'm sorry, it is 3181. 14 Q. Under familicide suicide, you write, 15 "Clinicians encountering the depressed senior male of 16 the household should consider the risk of familicide 17 suicide." Would you explain to us what familicide 18 suicide is? 19 A. In my article I called it familicide because we 20 saw a number of cases where not only the spouse was 21 killed, but the children were also killed, so it was 22 the whole family that was killed by the depressed man. 23 In the article we're pointing out, some of the 24 clinical implications of this and pointing out that 25 this is a possibility, a rare possibility, but PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2009 1 something that a clinician should consider. As I 2 said, oftentimes, it's not just the spouse, but the 3 children as well that are killed. 4 Q. On down in that same section you write, "In the 5 United States, the perpetrators of familicide are 6 almost exclusively male. Often the precipitance 7 include cumulative financial, marital, or other social 8 stresses on the family." 9 We need to have you define a word or two in 10 there. You use the term precipitance. What does that 11 mean? 12 A. An immediate cause. We often found that the 13 immediate cause of the murder/suicide was that of 14 stresses within the family, on the family. And again, 15 this could be either financial considerations or other 16 changes in jobs, for example, other social stresses on 17 the relationship. 18 Q. Now, down at the bottom of that section you 19 have written, "Some investigators have stressed 20 dependent protective motives; that is, the senior male 21 commands a relationship in which he perceives that 22 only he can satisfy the needs of the victims. When 23 this relationship is threatened, he erupts in a 24 frustrated homicidal/suicidal rage." Would you 25 explain that concept for the jury, please? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2010 1 A. Okay. A few authors have found, as I said 2 earlier -- it is sort of paraphrasing what I said 3 earlier -- that the senior male is used to controlling 4 what's in the family. He feels that the family 5 depends on him, but yet something changes. He becomes 6 depressed, he loses his job, or some other stress puts 7 him in a subservient position, a dependent position, 8 which is something that is intolerable, so in addition 9 to being depressed, his self-esteem in relation to 10 what he used to be in the family, is undermined. 11 Q. Now, I want to ask you about another statement. 12 This is over on 3182 in the middle of the column where 13 you say, "The murders of blood relatives, either in 14 child killing or familicide, appear to represent 15 extended suicides." And I want you to explain to the 16 jury what is the concept of extended suicide that 17 you're discussing here. 18 A. Well, it's more or less a psychoanalytic term, 19 but plainly spoken, it's -- the family represents 20 projections of the man, okay, so that he's killing not 21 necessarily the family, but himself what's projected 22 onto them. 23 Q. I want to ask you about another article. This 24 is Milton Rosenbaum. Do you have that? 25 A. Yes, I did bring that one up to the stand. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2011 1 Q. Let me refer you, again, to your paper and ask 2 you to explain one more concept. You write on 3 Page 3182 in the left-hand column at the bottom, you 4 say, "Nevertheless, we believe the most convincing 5 unifying diagnosis common to all subtypes of 6 murder/suicide is depression." Could you tell the 7 jury, has that been a finding across the literature on 8 homicide/suicide that you've reviewed? 9 A. On homicide/suicide done by older males, yes, 10 depression is a core thing. It's also very core in 11 terms of women who kill children, which is another 12 type of murder/suicide which I haven't gotten into. 13 Oftentimes the woman is very depressed and kills a 14 newborn. 15 Q. We're not involved in that. 16 A. No, I'm not involved in that. I'm just talking 17 about spouse, lovers murder/suicides. 18 MR. SEE: Very good. I pass the witness. 19 Thank you, sir. 20 CROSS-EXAMINATION 21 BY MR. VICKERY: 22 Q. Hello, Dr. Tardiff. 23 A. Hello. 24 Q. My name is Andy Vickery. I have pledged to get 25 you out of here by four o'clock. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2012 1 A. Bless you. 2 Q. What are your financial arrangements with Eli 3 Lilly for testifying as an expert in this case? 4 A. I'm paid $300 an hour for anything that I do, 5 which includes reviewing records, testimony, and so 6 on. 7 Q. Or $3,000 a day? 8 A. Or $3,000 a day. 9 Q. And can you tell us to date, including the time 10 that you've spent down here, if you were to suddenly 11 be blipped home to New York, what would the total 12 charge be? 13 A. I haven't done that calculation yet, but I 14 would say that it would be four days. 15 Q. So $12,000? 16 A. 12,000 for my time here. 17 Q. Now, do you call yourself a suicidologist, is 18 that a term you would use to describe yourself? 19 A. No, I would call myself an expert on suicide 20 and homicide. 21 Q. Are you a member of the American Association of 22 Suicidology? 23 A. No. 24 Q. The International Association for Suicide 25 Prevention? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2013 1 A. No. 2 Q. The American Academy of Forensic Sciences? 3 A. No. 4 Q. The American Foundation for Suicide Prevention? 5 A. No. 6 Q. Academy for Suicide Research? 7 A. No. 8 Q. American Academy of Forensic Examiners? 9 A. No. 10 Q. Have you published any books on suicide? 11 A. Yes. Books? I've published books where 12 suicide was a topic, yes. 13 Q. Okay. Do you know, either personally or by 14 reputation or by familiarity with the works, Dr. Ron 15 Maris? Do you know Dr. Maris' work? 16 A. I know of his work, yes. 17 Q. I mean, he's got like 16 books and a zillion 18 articles on suicide. 19 A. I really don't know that. 20 Q. Now, tell me this, in this case, your report -- 21 you prepared a report about the opinions you were 22 going to give here, didn't you? 23 A. Correct. 24 Q. And in that report you said that the 25 murder/suicide involving the Forsyths -- would you two PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2014 1 leave? I'm sorry, I should have thought about that -- 2 is a typical case resembling other cases that you've 3 reviewed? 4 A. That's correct. 5 Q. How many of the 128 cases of murder/suicide in 6 New York that you studied involved older men killing 7 their spouse and then themselves? 8 A. That's hard to say at this point. Fifty-seven 9 involved spouse lovers and it's hard for me to 10 remember the break down of the young men versus the 11 old men at this time, but 57 percent involve spouse 12 lovers. 13 Q. And the vast majority of those were young men 14 killing their -- killing out of jealousy? 15 A. No, I would say half and half. 16 Q. Half and half? 17 A. Yeah. 18 Q. What you said in this case is that the primary 19 motive is suicide and the man kills his wife to spare 20 her the grief of his death and/or stresses in their 21 lives? 22 A. Not only to spare her. There's also anger in 23 many cases. 24 Q. Now, your report in this case says nothing 25 about anger, does it? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2015 1 A. No, it didn't say anything about anger. 2 Q. What your report says is the primary motive is 3 to spare her the grief? 4 A. Yes. 5 Q. Have you seen the autopsy report? 6 A. Yes. 7 Q. Have you seen the photographs? 8 A. Yes. 9 Q. Do you -- you know from your expertise in 10 violence and suicide what a defensive cut is, don't 11 you? 12 A. Yes. I'd like to elaborate on this answer, 13 though. In a classic study by Wolfgang, he found that 14 most of the murder/suicides involved multiple 15 injuries; that is, multiple stab wounds and multiple 16 shootings, so this fits into that pattern very 17 clearly. 18 Q. Well, the rage -- are you saying this is a 19 mercy killing? 20 A. No. No, this is not a mercy killing. 21 Q. It's nothing like a mercy killing, is it? 22 A. No, not at all. 23 Q. And you say Bill Forsyth killed June, stabbed 24 her as many times as he did, when she was trying to 25 defend herself and getting these defensive cuts to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2016 1 spare her the grief of his death? 2 A. No. 3 Q. Well, why did you write that in your report 4 here? The primary -- I'm just reading your report. 5 "The primary motive is suicide and the man kills his 6 wife to spare her the grief of his death and/or the 7 stresses in their life." 8 A. I think he was angry as well. I didn't put it 9 in my report, you're right. 10 Q. Okay. Now, what you did put in your report is 11 that he and his wife were incompatible? 12 A. Yes. 13 Q. On what did you base that opinion? 14 A. On a number of the records of Dr. Brady, a 15 number of depositions. What was apparent is that -- 16 I'm sure the jury has heard this. They had a style, a 17 relationship which was long enduring where he would 18 not talk to her, reject her, she would try to get him 19 to talk and there was this conflict, which was long, 20 long -- which existed for a long time. 21 I think eventually, as he became depressed, as 22 he went into retirement and had nothing to do, they 23 were tossed together, and I think what happened at 24 that point in time is that he realized that the 25 marriage -- that they were incompatible, but yet at PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2017 1 that point in time, he was very dependent on her, so I 2 think he thought there was really no way out. 3 Q. Now, at that point in time are you talking 4 about 1993, after he and June finished their therapy 5 with Tom Brady, is that when you're saying they were 6 incompatible? 7 A. Yes. 8 Q. Now, have you learned from anyone, from Mr. See 9 or anyone else, what evidence the jury has heard about 10 how they were relating after that? 11 A. Yes. I think they were relating better. 12 Dr. Brady states that they had a better way of 13 communicating, but at the time that he killed his wife 14 then himself, I still think they had marital problems. 15 Q. I want to ask you to assume five things for me. 16 A. Okay. 17 Q. To assume that his best friend of 50 years, 18 David Capelouto said that Bill told Mr. Capelouto, the 19 marriage was better than ever, even the sex; that her 20 closest friend, Bobbie Comstock, said that on the very 21 day that they were killed, that she said, I'm not 22 going to pray and fast with you all today. I'm going 23 to have Mexican food and go get my Bill; that Dr. Neal 24 said both Bill and June told him their relationship 25 was better than ever; that they told their daughter PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2018 1 Susan, who I asked to leave the room because of what 2 we're talking about, that they were on their second 3 honeymoon, it was like a second honeymoon; and I 4 forgot the fifth one I was going to ask you. Now, 5 assuming those things -- oh, and that Dr. Brady 6 himself confirmed that they had a -- what he called a 7 freshening of intimacy, after they finished in 8 December of '92, they were intimate, they were open, 9 they were communicating. 10 If that's the evidence in this case, do you, 11 sir, still believe that Bill and June Forsyth were 12 incompatible on March the 3rd of 1993? 13 MR. SEE: Your Honor, I object to the 14 hypothetical because it contains no specific reference 15 to time. It's incomplete. It doesn't hypothesize the 16 facts necessary to answer it, as to when these things 17 took place. 18 THE COURT: Well, why don't you try to put it 19 in time. 20 MR. VICKERY: Okay. I will, Your Honor. 21 Q. Assume Bobbie Comstock said on the day they 22 died, March 3, 1993, that she was going to go with her 23 Bill. She was going to have Mexican food and be with 24 her Bill; that Dr. Neal said that both of them 25 confirmed to him in the period from February 24th to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2019 1 March 3rd, the week before their deaths, their 2 marriage was better than ever; that Dave Capelouto 3 confirmed that his friend of 50 years, Bill Forsyth, 4 told him towards the end of the therapy with 5 Dr. Brady, which would have been end of November, 6 early December '92, that it was a better relationship 7 than ever, including the sex; that Dr. Brady testified 8 that in December, when they ended their therapy, they 9 had this freshening of intimacy and they were talking 10 and that that was confirmed in two telephone 11 conversations, the last of which was two weeks before 12 their death; and that Susan testified that it was 13 right near the end of their therapy, in mid to late 14 November of '92, that they were going on a second 15 honeymoon. 16 If that's the evidence in this case, do you 17 believe that they were incompatible? 18 A. I still think they had core marital problems. 19 Definitely. 20 Q. Okay. 21 A. This is based on my review of the case and also 22 my clinical experience. 23 Q. And you feel like that he had no way out, so he 24 killed her? 25 A. Yes, that's what he believed. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2020 1 Q. Now, one of the things you say is that there 2 are frequently suicide notes in this familicide 3 suicide, and the suicide note suggests the murderers 4 see themselves as altruistically delivering the family 5 from continued hardships? 6 A. Yes. 7 Q. You know there's no suicide note in this case, 8 don't you? 9 A. That's right. 10 Q. You also say that in this kind of relationship, 11 the senior male commands a relationship in which he 12 perceives that only he can satisfy the needs of the 13 victims. Now, if all the evidence is that Bill 14 Forsyth thought he was dependent on June, not vice 15 versa, he was dependent on her, that doesn't fit the 16 pattern that you write about either, does it? 17 A. But that's the point, he shifts from a place 18 where he was in control to a place of dependency. To 19 him this was unacceptable. 20 Q. Have you ever -- you've mentioned the articles 21 you published. Have you ever published in The Journal 22 of Suicidology? 23 A. No. I like to publish in places where it would 24 get maximum exposure. 25 Q. Okay. I just have about three more for you. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2021 1 A. Okay. Thanks. 2 Q. Do you know who Sir Austin Bradford Hill is? 3 A. No. 4 Q. Now, one of the studies you did among 4,298 5 workers in New York in 1990 and '91 focused on 6 violence, did it not? 7 A. I beg your pardon? Which article was that? 8 Q. It's not a published article. It's something I 9 found in the press. You did a study in New York of 10 4,298 workers in 1990 and '91, did you not? 11 A. Are you talking about homicides? 12 Q. Yes, sir. 13 A. Homicides, yes. Right. 14 Q. Okay. And with respect to those, did you find 15 that some of them had committed these violent acts 16 while under the influence of a drug which is known to 17 effect serotonin? 18 A. What are you referring to? Cocaine? 19 Q. Cocaine. 20 A. Yes. Yes. 21 Q. Okay. Sir, now finally, since you tell us your 22 emphasis is epidemiology, if one is looking for a 23 phenomenon, a drug-induced phenomenon that is fairly 24 rare, that doesn't affect a large percentage of the 25 people that take it -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2022 1 A. Yes. 2 Q. -- and if one wants to study that through 3 epidemiology, do you have to have a real large patient 4 population to really have a valid study? 5 A. Yes, you would. 6 Q. How large? 7 A. This involves power calculations and so on. I 8 would have to rely on my statistician for that. I 9 can't tell you. It would have to be literally 10 thousands. 11 MR. VICKERY: Thank you very much, Dr. Tardiff. 12 REDIRECT EXAMINATION 13 BY MR. SEE: 14 Q. Doctor, I have only one question for you to 15 follow up Mr. Vickery's question about violence and 16 level of serotonin activity. Is violence associated 17 with a high level of serotonin activity or a low 18 level? 19 A. It is associated with a low level of serotonin 20 activity. 21 MR. SEE: That's all. Thank you, sir. 22 THE COURT: Anything more, Mr. Vickery? 23 MR. VICKERY: I don't think so, Your Honor. I 24 promised to get him out at four. 25 THE WITNESS: Thank you. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2023 1 THE COURT: Well, I guess you get to go home. 2 THE WITNESS: Thank you, Judge. 3 THE COURT: It's four o'clock. We'll all go 4 home. I want to tell the jury though, again, we will 5 not be meeting on Monday. Our next session will be on 6 Tuesday at nine, so please be back then. 7 Also, next week, we will not be meeting on 8 Friday. I believe that's Kuhio Day, Prince Kuhio Day, 9 so have a nice weekend. 10 (Whereupon, the proceedings were adjourned at 11 4:00 p.m. to be reconvened on Tuesday, 12 March 23, 1999 at 9:00 a.m.) 13 14 15 16 17 18 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2024 1 C E R T I F I C A T E 2 --ooOOoo-- 3 I, TINA M. STUHR, Official Court Reporter, 4 United States District Court, District of Hawaii, 5 Honolulu, Hawaii, do hereby certify that the foregoing 6 is a correct partial transcript of proceedings in 7 Civil No. 95-00185ACK, Susan K. Forsyth, et al. vs. 8 Eli Lilly and Company, et al., at Honolulu, Hawaii, on 9 March 19, 1999, before the Honorable Alan C. Kay, 10 United States District Judge. 11 DATED: December 27, 1999. 12 13 ______________________________________ TINA M. STUHR, RPR, CSR #360 14 15 16 17 18 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU