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 woul