1 A. I don't know offhand how 2 they're scoring that. 3 MS. ZETTLER: Let's quit for the day. 4 * * * * * * * * * * 5 THE DEPOSITION WAS ADJOURNED FOR THE DAY. 6 THE DEPOSITION CONTINUED THE FOLLOWING DAY, 7 APRIL 28, 1994, AS FOLLOWS: 8 * * * * * * * * * * 9 CONTINUED DIRECT EXAMINATION 10 BY MS. ZETTLER: 11 Q. Okay. Doctor, my voice is 12 even worse than it was yesterday. In fact, I 13 couldn't actually talk for the first ten minutes 14 this morning, so I may need something later, so 15 please bear with me. Yesterday we were talking 16 about the process you went through to analyze the 17 DEN data base and the clinical trial data base 18 for your aggression article. Do you remember 19 that? 20 A. Yes, I do. 21 Q. And so I make sure I get your 22 testimony down right, you ran the event terms 23 listed in Exhibit 1 through the DEN data base, 24 correct? Page 299 1 A. That's correct. 2 Q. But not all of those events 3 were run through the clinical trial data base, 4 right? 5 A. That's correct. 6 Q. Okay. Do you recall how many 7 events or 1639s were kicked out of the DEN data 8 base as a result of the analysis of the events 9 listed in Exhibit 1? 10 A. I do not recall a number. 11 (PLAINTIFFS' EXHIBIT NO. 2 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Have you had a chance to 15 review Exhibit 2? 16 A. I have. 17 Q. Exhibit 2 appears to be two 18 copies of -- or in part appears to be two copies 19 of an E-mail written by you dated January 2, 20 1990, correct? 21 A. That's correct. 22 Q. And the first copy or the 23 first page of the exhibit is a clean copy of the 24 E-mail without any handwritten notes on it, Page 300 1 correct? 2 A. That's correct. 3 Q. And the second copy of that, 4 looks like a bunch of numbers written in? 5 A. That's correct. 6 Q. Is that your handwriting? 7 A. No, it is not. 8 Q. Do you recognize the 9 handwriting? 10 A. No, I do not. 11 Q. And then the third page is a 12 printout dated February 16, 1990 entitled 13 "Aggression In Ongoing prozac Clinical Trials." 14 Correct? 15 A. Yes. 16 Q. Okay. Do you recall writing 17 the E-mail that is represented on the first two 18 pages of Exhibit 2? 19 A. I do recall sending this 20 particular message and preparing that message. 21 Q. What does this listing 22 represent in the middle? 23 A. This reflects the terms that 24 we reviewed that we pulled from the DEN data Page 301 1 base. 2 Q. The terms that are listed in 3 Exhibit 1? 4 A. Yes, ma'am. 5 Q. In the top part of the E-mail, 6 it says, "Comrades, I have searched the following 7 terms in an effort to identify patients who may 8 have exhibited violence towards others. The 9 number reflects the total number of spontaneous 10 and trial events available for review through 11 late December." Do you see that? 12 A. Yes. 13 Q. What do you mean when you say 14 spontaneous and trial events? 15 A. I am not sure. What it may 16 mean is that the DEN data base was searched for 17 all such events that had been reported. And for 18 a trial event reported during the trial, it would 19 have had to have been an alert report. 20 Q. So alert reports in the DEN 21 data base that reflect alert type events that 22 happened in the trials? 23 A. I suspect that would be the 24 case. Page 302 1 Q. These numbers don't include 2 the numbers of adverse events falling under these 3 categories that occurred in the clinical trial 4 data base generally? 5 A. No, they do not. 6 Q. So these numbers are really 7 just from the DEN data base? 8 A. That's correct. 9 Q. I took the liberty of totaling 10 these up last night, Doctor, and if you can rely 11 on my representation or add them up yourself, if 12 you like, but I counted eleven hundred and 13 fifteen total events on this list. Does that 14 refresh your recollection as to how many you 15 reviewed in your initial review of the DEN data 16 base? 17 A. I recall I reviewed a large 18 number of events. 19 Q. And yesterday you said that 20 after you had reviewed it and Doctor Beasley had 21 reviewed it, and you reviewed the one part that 22 Doctor Beasley reviewed, you narrowed it down to 23 approximately eleven adverse event reports? 24 A. Where -- yes, somewhere in Page 303 1 that vicinity. 2 Q. So is it your testimony that 3 the remaining eleven hundred and one reports were 4 culled out by either you or Doctor Beasley or 5 both you and Doctor Beasley because they either 6 did not represent an injurious act towards others 7 or because there was some other reason that may 8 have contributed to the acts reflected in the 9 report? 10 A. To the best of my 11 recollection, the vast majority of those events 12 were excluded because there was no suggestion 13 within those events of hostility or agressivity 14 towards others. 15 Q. And again, so I'm clear, a 16 decision was made not to include or do an 17 analysis on these events in and of themselves 18 without some act or verbalization of intent to 19 injure somebody else as was reflected in the 20 1639? 21 A. Could you repeat that, please? 22 Q. Sure. Even though there's 23 eleven hundred and fifteen acts listed here, 24 okay, a decision was made to cull out or not Page 304 1 consider or not use in the analysis these acts 2 unless they either showed an act of aggression 3 towards somebody else or a verbalization of an 4 intent or wish to commit an act towards somebody 5 else, correct? 6 A. That's a long question. 7 Q. Read it back if you want. 8 MR. MYERS: Do you want her to read it 9 back? 10 THE WITNESS: Once again, please. 11 (THE COURT REPORTER READ BACK THE 12 REQUESTED TESTIMONY.) 13 A. A decision was made in advance 14 of undertaking these processes to the cascade of 15 how the data would be handled, and yes, that 16 would have been part of that earlier planning 17 process. 18 Q. Okay. And is it fair to say 19 that some of these adverse events listed in and 20 of themselves would indicate risk factors for 21 somebody becoming more violent aggressive? 22 A. They may. 23 Q. And that wasn't taken into 24 consideration, the fact that somebody may have Page 305 1 been -- may not have been actively violent 2 aggressive towards somebody else, but they were 3 at least exhibiting some risk factors towards 4 becoming more aggressive towards somebody else? 5 A. Depression itself is a risk 6 factor, and that was taken into consideration, 7 yes. 8 Q. So then why weren't all these 9 analyzed, why weren't all one hundred and fifteen 10 taken into consideration in the analysis -- I'm 11 sorry, one thousand one hundred and fifteen? 12 A. Which analysis are you 13 speaking of? 14 Q. The original initial analysis 15 in the DEN data base. 16 A. They were all reviewed. 17 Q. Right. But why didn't you 18 just rerun all of these adverse events in the 19 clinical trial data base since some of them at 20 least represent risk factors for people becoming 21 aggressive? 22 A. That would have been 23 misleading and unscientific. 24 Q. According to who? Page 306 1 A. According to good science, in 2 my best estimation. 3 Q. Can you point me to a resource 4 outside of Lilly that determines that the way you 5 did this analysis was good science? 6 A. I think you would do well to 7 consult with experts in the field of 8 epidemiology. 9 Q. Besides Doctor Kotsanos, who 10 was an employee of Lilly, you did not consult 11 with anybody else in the field of epidemiology 12 for this project, correct? 13 A. No, we did not. 14 Q. Let's turn to the second page 15 of the exhibit. It looks as if somebody had gone 16 through and either subtracted numbers from these 17 various adverse event listings or added, and I 18 readded the totals here based on this person's 19 circled figures, and the total in this list adds 20 up to twelve hundred and sixteen. Do you have a 21 recollection of either acts being added or 22 subtracted from these various categories? 23 A. I don't have that 24 recollection. Page 307 1 Q. Do you know if the total 2 number of 1639s that you reviewed was one 3 thousand one hundred and fifteen as reflected in 4 your original E-mail or closer to twelve hundred 5 and sixteen as reflected in the second page of 6 this? 7 A. I don't recall. 8 Q. Could this have been Doctor 9 Masica's notes on the second page of this 10 exhibit? 11 A. I do not recognize that as 12 Doctor Masica's writing. 13 Q. Could you recognize Doctor 14 Masica's writing if you saw it? 15 A. I believe I could. 16 Q. Okay. Back on the first page, 17 it says, "The number reflects the total number of 18 spontaneous and trial events available for review 19 through late December." Are you talking about 20 December, 1989 there? 21 A. Yes, ma'am. 22 Q. Why wasn't anti-social 23 behavior one, or anti-social reaction? 24 A. It may have been that Page 308 1 anti-social behavior tracked to personality 2 disorder. Apart from that I don't -- that's my 3 best explanation, and that's a -- 4 Q. Would that be the same as 5 anti-social reaction? Because I misstated it, it 6 wasn't anti-social behavior, it's anti-social 7 reaction that's listed on Exhibit 1. 8 A. Yes, ma'am. 9 Q. Well, Doctor, according to the 10 ELECT dictionary that has been given to us by Eli 11 Lilly, anti-social reaction is a ELECT 12 classification term in and of itself. 13 A. Okay. 14 Q. Given that, do you know why 15 anti-social reaction was not run in the DEN data 16 base as one of the search terms? 17 MR. MYERS: Assuming that that's the 18 case as of the time the report was run? 19 MS. ZETTLER: Well, we've been -- 20 Larry, you told me that that's the one that is 21 relevant to this case. 22 MR. MYERS: I don't know that I told 23 you that, I'm just telling you that I don't -- 24 this postdates this run. I'm not saying that Page 309 1 it's different or not, I'm saying assuming it's 2 the same. Is that what your question assumes? 3 MS. ZETTLER: Yes, from what you told 4 me. 5 MR. MYERS: Well. 6 MR. SMITH: We assumed that we could 7 use that in connection with questioning 8 witnesses, based on your representation that it 9 was applicable to these cases. 10 MR. MYERS: You may use it in 11 connection with questioning witnesses. I don't 12 know that I made such a representation that it 13 was applicable to these cases. 14 MR. SMITH: Do you deny that you made 15 such a representation? 16 MR. MYERS: I have no recollection of 17 making that representation. 18 MR. SMITH: Do you deny making that 19 representation? 20 MR. MYERS: I'm not here to be 21 examined, Mister Smith. 22 MR. SMITH: Well, in order to properly 23 examine the witness, we need to have some concept 24 with respect to whether or not we have the right Page 310 1 ELECT, Costart dictionary being used in 1990, and 2 if it's not, then we don't have the proper way to 3 cross-examine this witness. 4 MR. MYERS: Well, I'm not here to be 5 examined. I simply asked a question about what 6 your question assumed. 7 MR. SMITH: Your question implies that 8 this may not be applicable to this case, and if 9 it's not, we need to know that in order to 10 properly examine this witness. Otherwise our 11 questions naturally can be interpreted in several 12 different ways, and it gives this witness the 13 opportunity to later claim that our questions in 14 this regard were not relevant because we weren't 15 using the right dictionary. 16 MR. MYERS: Right. I have no problem 17 in you questioning the witness about this 18 dictionary as relates to these several documents. 19 I don't know the answer to the question that you 20 posed, Mister Smith, and that's the only reason 21 that I raised it. 22 MS. ZETTLER: My recollection of what 23 happened is when we requested copies of the ELECT 24 dictionary, the representation was made that this Page 311 1 is the only dictionary that now exists, still 2 exists, and that it is the dictionary in the form 3 that is relevant for all periods of time in this 4 litigation. 5 MR. MYERS: Nancy, I simply do not 6 have that recollection. If there's some writing 7 where I said that, I'll certainly stand to be 8 corrected, either some writing or some pleading 9 that I or somebody else has signed. 10 MS. ZETTLER: If there were other 11 volumes of this, if this is changed materially, 12 or in any respects, since before 1990 -- between 13 1989, when this occurred, and 1991, when this 14 printout of this dictionary was made, then we 15 want copies of all forms of this dictionary, not 16 just the one that you produced that represents -- 17 that's represented here in this volume. Either 18 that or a listing of what changes were made over 19 the years. But like, for instance, anti-social 20 reaction was added after this computer analysis 21 was run that we've been talking about, I think we 22 have a right to know that, and I think, you know, 23 I'm making a request that you find out whether or 24 not that is in fact the case. Page 312 1 MR. MYERS: I didn't follow that. I 2 thought that I'm looking at anti-social reaction 3 in here. 4 MS. ZETTLER: Right, but that's dated 5 1991. Doctor Heiligenstein's -- 6 MR. MYERS: No, it's not. 7 MS. ZETTLER: The printout is dated 8 January, 1991. 9 MR. MYERS: No, it's not. It's dated 10 January 16, 1990, it's like a two-week thing. I 11 just don't know, that's my point. 12 MS. ZETTLER: All right. 13 Q. (BY MS. ZETTLER) Do you have 14 any recollection, Doctor, as to whether or not 15 anti-social reaction was added as an event term 16 after the computer analysis of the DEN data base 17 that you did was run? 18 A. No, it's -- on reflection it 19 appears to me that that was indeed run, and there 20 were no events within that -- with that ELECT 21 term in the DEN data base. 22 Q. How do you know that? 23 A. That would be my recollection 24 because it would not -- it would have appeared Page 313 1 here if there were some, and as I recall we did 2 review all of these terms. 3 Q. And -- but it wasn't listed on 4 here as not having any, though, correct? 5 A. It was not. 6 Q. Is that your normal procedure, 7 if there isn't something that's listed under an 8 event term such as this, you just don't list it 9 on here or list it, or is it more typical that it 10 would list zero under the event term if there 11 were none? 12 A. With the intent of this 13 message, it would not have listed necessarily all 14 events, even if there would have been no such 15 events. 16 Q. But you specifically used 17 anti-social reaction as one of the events, 18 aggression cluster events, correct? 19 A. As I recall. 20 Q. That's correct, as you recall? 21 A. That's correct. 22 Q. If you didn't have any events 23 that popped up in the DEN dictionary, how is it 24 that you chose that event to run as one of the Page 314 1 aggression cluster events? 2 A. I don't recall the specifics 3 of that. 4 Q. Could it be because you knew 5 it wasn't going to come up on any events in the 6 clinical trial data base? 7 A. I don't know that answer, that 8 would not be the reason. 9 Q. Who would know why anti-social 10 reaction was used as one of the three cluster -- 11 aggression cluster events for review of the 12 clinical trial data base even though no 1639s 13 came up during your DEN review of that adverse 14 event term? 15 A. Let me just clarify. I said 16 it's likely that there were no such events, and 17 that's why it did not appear on this particular 18 messenger note. It may well have been that given 19 the likelihood that in a clinical trial an 20 investigator may have ascribed some such behavior 21 to -- or tracked it to anti-social reaction, that 22 we felt should be included in that analysis or 23 data base search of the clinical trials. 24 Q. Mapped what to anti-social Page 315 1 reaction? 2 A. Some behavior. 3 Q. Couldn't that be said for 4 every single event that's listed in Exhibit 2, 5 such as agitation, which has three hundred and 6 ninety-one 1639s that came up in your search? 7 A. No, it's more likely that an 8 investigator with experience in doing such trials 9 would very likely have ascribed that type of 10 behavior to an individual with an anti-social 11 personality. 12 Q. Why? 13 A. That's more or less the 14 standards that psychiatrists use. 15 Q. Based on what? 16 A. Clinical experience, quite 17 often, for individuals for which there is no 18 other explanation. 19 Q. What about hostility? 20 MR. MYERS: What about it? 21 Q. Would they be likely to map 22 violent acts towards hostility? 23 A. They might. 24 Q. What about personality Page 316 1 disorder? 2 A. That would be possible. 3 Q. How about paranoid reaction? 4 A. The question again? 5 Q. Wouldn't psychiatrists map 6 violent behaviors towards paranoid reaction? 7 A. Only in the context of the -- 8 of a paranoid episode. 9 Q. In fact, people who suffer 10 paranoid delusions are at high risk factor for 11 committing violent acts towards others, arent' 12 they? 13 A. There is a risk factor. 14 Q. But you didn't run that one on 15 the clinical trial data base? 16 A. No, we did not. 17 Q. But you ran anti-social 18 reaction even though no 1639s came up on your 19 initial search on the DEN data base? 20 A. To the best of my 21 recollection, there were no such events. 22 Q. Okay. 23 A. It may have been an oversight, 24 as well, in this particular message. Page 317 1 Q. Let's go back to my initial 2 question, which I don't think you responded to. 3 Who would know who would have made that decision 4 to use anti-social reaction as an adverse event 5 term to search the clinical trial data base? 6 A. That would have been a 7 decision most likely made by myself and Doctor 8 Beasley. 9 Q. You don't have any specific 10 recollection of making that decision? 11 A. I do not. 12 Q. Is the -- are there any notes 13 of meetings between you and Doctor Beasley where 14 that decision was made? 15 A. I don't recall that there 16 would be any notes from that meeting. 17 Q. Would anybody else have been 18 involved in that decision besides you and Doctor 19 Beasley? 20 A. Not that I recall. 21 Q. The last page of Exhibit 2 is 22 a computer printout. Do you recognize that? 23 A. I have a vague recollection. 24 Q. Tell me what your recollection Page 318 1 of this is, what do you remember about it? 2 A. This appears to be the 3 computer search of the events of the aggression 4 cluster. 5 Q. Okay. So this is the result 6 of the search of the three adverse events that 7 were determined would make up the aggression 8 cluster, correct? 9 A. That's correct. 10 Q. Is this the entire printout, 11 the entire result of the entire search? 12 A. As best I recollect, yes. 13 Q. The bottom of the page it 14 says, "The following single dose studies are not 15 included in this report." And it lists a number 16 of studies, does it not? 17 A. That's correct. 18 Q. What does a single-dose study 19 mean? 20 A. These are usually studies that 21 are done early in the clinic in volunteer 22 patients. 23 Q. Okay. These are not 24 double-blind controlled studies, to your Page 319 1 knowledge? 2 A. I don't recollect that they 3 were. 4 Q. Do you recognize any of these 5 studies listed at the bottom of the page as being 6 double-blind controlled studies? 7 A. I do not. 8 Q. Did you search both the United 9 States clinical trials and the outside the United 10 States clinical trials for this project? 11 A. I don't recall. 12 Q. You don't recall either way? 13 A. I don't recall. 14 Q. Who would know that? 15 A. I believe it would be in the 16 methodology section of the paper. 17 (PLAINTIFFS' EXHIBIT NO. 3 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Can you tell us what Exhibit 3 21 is? 22 A. This is a manuscript which was 23 submitted for publication. 24 Q. Okay. It's a manuscript of Page 320 1 your violent aggressive behavior paper, correct? 2 A. It's the -- that's correct. 3 Q. Have you had a chance to 4 review that exhibit? 5 A. Not the complete paper, no. 6 Q. Well, you don't have to look 7 at the whole thing, but have you been able to 8 find out whether or not you ran the search of the 9 aggression cluster on U.S. trials or U.S. and OUS 10 trials both? 11 A. Yes, I have been able to 12 establish that. 13 Q. And what -- did you run it on 14 both the U.S. and OUS or just the U.S.? 15 A. U.S. IND trials. 16 Q. Why didn't you run it on the 17 OUS trials also? 18 A. As I best recollect, from the 19 start of the process we felt that we would focus 20 on the U.S. clinical trial data base. 21 Q. Why? 22 A. We felt that there would be -- 23 as I best recollect, we would have sufficient 24 information to complete such an analysis. Page 321 1 Q. Double-blind controlled 2 studies were conducted outside the United States 3 on Fluoxetine, were they not? 4 A. Yes, they were. 5 Q. And if you wanted to be 6 thorough, as you represented to us yesterday that 7 you wanted to be on this project, wouldn't it 8 have been more thorough to search both the 9 double-blind controlled studies conducted in the 10 United States as well as the double-blind 11 controlled studies conducted outside the United 12 States? 13 A. One could make that argument. 14 Q. Would it be better science to 15 have searched the double-blind controlled studies 16 conducted outside the United States also? 17 A. Not necessarily. 18 Q. Why not? 19 A. Because the science of the 20 methodology of this particular effort, I think, 21 is very tight and appropriate for the question 22 that was asked. 23 Q. Let's go back to the last page 24 of Exhibit 2, please. Twenty-six total patients Page 322 1 are listed on the third page of Exhibit 3, 2 correct? 3 A. I'll count them. 4 Q. Go ahead. 5 A. That's correct. 6 Q. Okay. And out of those 7 twenty-six, fourteen are from depression trials, 8 correct? 9 A. That's correct. 10 Q. And four are from bulimia 11 trials? 12 A. Correct. 13 Q. Four are from obesity trials? 14 A. That's correct. 15 Q. And four are from smoking 16 trials? 17 A. That's correct. 18 Q. Out of the ten depression 19 trial people, all but one were on Fluoxetine, 20 correct? 21 MR. MYERS: Did you say ten? 22 MS. ZETTLER: Did I say ten? 23 MR. MYERS: You did say ten. 24 Q. Fourteen, I'm sorry. Out of Page 323 1 the fourteen people in the depression trials, all 2 but one were on Fluoxetine, correct? 3 A. That's correct. 4 Q. Can you tell from this page 5 whether or not these people popped up under the 6 hostility adverse event as opposed to the 7 anti-social reaction event? 8 A. I cannot. 9 Q. Okay. Were all of these 10 twenty-six people included in the analysis that's 11 reflected in your paper, Doctor? 12 A. I do not believe they were. 13 Q. Why not? 14 A. Some of these may have been 15 from unblinded studies, some of these may have 16 been from -- may not have been in comparator or 17 placebo controlled studies. 18 Q. I thought you just ran the 19 analysis on those double-blind controlled 20 studies? 21 A. This run appears to be for 22 patients in Prozac clinical trials. 23 Q. How do you know that? 24 A. That's what it says. Page 324 1 Q. Well, can you tell from this 2 whether or not these people were in double-blind 3 controlled studies or not? 4 A. I can tell from some of these 5 project codes that some of these were not 6 double-blind comparator placebo controlled 7 studies. 8 Q. Which ones? 9 A. HCDL was not, I believe that 10 HCCD was not. 11 Q. Any others? 12 A. There may be, but those are 13 two that come to mind. 14 Q. So your testimony now is that 15 the aggression cluster adverse events search was 16 done on all U.S. clinical trials on Fluoxetine 17 across the board, whether or not they were 18 double-blind controlled? 19 MR. MYERS: I object to the form, I 20 don't think that's what he said, if you're trying 21 to capture his previous testimony. 22 MS. ZETTLER: I'm trying to clarify 23 what his testimony is because I think he's 24 changed it a couple of times now. Page 325 1 A. What this appears to be is a 2 run of events on patients in -- excluding those 3 patients in single-dose studies and patients who 4 were in the U.S. IND clinical trials, not 5 necessarily -- this is a printout -- would be a 6 printout of those patients, and would not exclude 7 patients who were in the nonplacebo, 8 noncomparitor controlled studies. 9 MS. ZETTLER: Could you read that 10 back? 11 (THE COURT REPORTER READ BACK THE 12 REQUESTED TESTIMONY.) 13 Q. So you're saying that this 14 printout represents a search of all of those 15 clinical trials done in the United States on 16 Fluoxetine except those listed at the bottom of 17 the sheet that are single-dose studies? 18 A. To the best of my knowledge. 19 Q. Regardless of whether or not 20 the study was double-blind, correct? 21 A. Regardless of -- to the best 22 of my knowledge, regardless of whether the study 23 was double-blind or whether there was a 24 comparator or placebo arm in the study. Page 326 1 Q. Which of these studies or 2 patients, to your knowledge, were patients that 3 were included in the final analysis that's 4 reflected in your paper? 5 A. It would be difficult for me 6 to know from these project codes specifically 7 which were patients. 8 Q. Which ones were not included? 9 A. To the best of my 10 recollection, this analysis would not have 11 included patients in study HCDL, nor patients in 12 HCCD. That's to the best of my recollection. 13 Q. Okay. What study is HCCD? 14 A. As as I recall, it's a -- it 15 may be the compassionate use protocol. 16 Q. Okay. And how about HCDL? 17 A. HCDL is the dose escalation 18 study. 19 Q. That's not double-blind 20 controlled? 21 A. It is double-blind controlled, 22 but it does not have a placebo or comparator arm 23 to the study. 24 Q. Then why is it double-blind Page 327 1 controlled? 2 A. Because there was a point in 3 the study when patients were rerandomized to 4 either the same or an increased dose of 5 Fluoxetine. 6 Q. So the doctors all knew that 7 they were on Fluoxetine, the patients were on 8 Fluoxetine, but they didn't know how much at any 9 given time, what dosage? 10 A. At some point in time, they 11 did not know what the patient's dosage was. 12 Q. Any other studies that are 13 listed here that you recognize as not having been 14 included in the final analysis? 15 A. There may be others, but I do 16 not recall specifics. 17 Q. What is study DFXO? 18 A. I don't recall. 19 Q. Excluding HCCD and HCDL takes 20 seven -- eight depression patients out of the 21 analysis, does it not? 22 A. I'm counting six unless 23 there's some -- I can count but six. 24 Q. You've got to look through the Page 328 1 little imprint that Lilly has placed over this 2 doctor, at the bottom of the HCDL line, there's 3 two other HCDL patients. 4 A. I still count but six. Oh, 5 I'm sorry, I -- 6 Q. You weren't including the 7 HCCD. My question was if you exclude the HCCD 8 patients and HCDL patients, that takes out eight 9 depression patients? 10 A. That's correct. 11 Q. And it just so happens that 12 all eight depression patients were on Fluoxetine, 13 were they not? 14 A. They could have been on 15 nothing else. 16 Q. Could have been on tricyclics? 17 A. Not in those studies. 18 Q. But they were all on 19 Fluoxetine, were they not? 20 A. That's correct. 21 Q. So you have eight depression 22 patients who are on Fluoxetine who popped up 23 during the search of the aggression cluster 24 events who were not included in the final Page 329 1 analysis, correct? 2 A. That's correct. 3 Q. How many total patients were 4 reviewed in the final analysis as a result of 5 this search? You can refer to your paper, 6 Exhibit 3, if you'd like. 7 A. Point of clarification, final 8 search being? 9 Q. Well, these are the people 10 that all popped up on the initial search of the 11 entire clinical trial data base in the United 12 States trials except for the single-dose studies, 13 correct? 14 A. That's correct. 15 Q. And we have already found out 16 through testimony this morning that a number of 17 these, at least eight, have been excluded, 18 correct? 19 A. That's correct. 20 Q. So you've got eighteen left on 21 the list that you know of, correct? 22 A. That would be correct. 23 Q. All right. I just want to 24 know from your paper how many of these actually Page 330 1 made it into the final analysis? 2 A. Thirteen. 3 Q. Okay. 4 MR. SMITH: Is it thirteen or 5 fourteen? 6 THE WITNESS: In this paper, it 7 appears to be thirteen. 8 Q. Okay. Who were the other five 9 patients on this list that's reflected in Exhibit 10 3 that were not included in the analysis? 11 A. They would have been patients 12 who, by a priori definition would not have been 13 eligible for analysis based upon their 14 participation in a noncomparitor or nonplacebo 15 controlled study. 16 Q. And you can't tell from this 17 list which of those patients they were? 18 A. I cannot. 19 Q. So you're saying that it's 20 your belief that there are other nonplacebo 21 controlled studies or nonplacebo double-blind 22 controlled studies listed in Exhibit 3 on the 23 third page -- or Exhibit 2 on the third page? 24 A. Yes, some of these studies Page 331 1 would be nonplacebo, noncomparitor controlled 2 studies. 3 Q. How about the bulimia studies, 4 do you recognize all of those as being 5 nonplacebo, noncontrolled studies? 6 A. Putting together the 7 information from the paper with this, since there 8 were four reported in the paper and four listed 9 from the bulimia trials, I would assume that was 10 a double-blind placebo or comparator controlled 11 study. 12 Q. How about the obesity studies? 13 A. That would appear to be a 14 placebo or comparator controlled study. 15 Q. Okay. How about the smoking? 16 A. That would appear to be the 17 case as well. 18 Q. So it appears that the other 19 patients came out of the depression studies as 20 well, that are listed, at least the ones on the 21 exhibit, Exhibit 2? 22 A. That's correct. 23 Q. Did I ask you if you know what 24 study DFXO is? Page 332 1 A. Yes. 2 Q. What was your answer? 3 A. I don't know, I don't recall. 4 Q. Were there other depression 5 studies that were included in the analysis that 6 aren't listed here on Exhibit 3? 7 A. Not that I recall. 8 Q. Well, I think we have a 9 problem with numbers here, then, Doctor. How 10 many depression studies are listed in the paper 11 having been analyzed? 12 A. The total number of trials 13 from which this data was drawn would appear to be 14 thirty-one. 15 Q. Okay. Thirty-one depression 16 trials? 17 A. I'm sorry, thirty-one total 18 trials, across all indications. 19 Q. Okay. Can you tell how many 20 depression trials were looked at? 21 A. Yes, there would be at least 22 seventeen. Possibly one of the adjustment 23 disorder trials could have been in patients with 24 adjustment disorder with depressed mood, but I Page 333 1 don't know that for sure. 2 (PLAINTIFFS' EXHIBIT NO. 4 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. Have you had a chance to 6 review Exhibit 4? 7 A. Yes, ma'am. 8 Q. Do you recognize this exhibit? 9 A. I have a vague recollection of 10 it. 11 Q. Tell me what you remember 12 about this exhibit. 13 A. As I now see it, it helps me 14 recall a document sent out by Doctor Masica that 15 summarizes the review of the hostility and 16 aggression. 17 Q. Did you draft any part of this 18 exhibit? 19 A. I suspect that I contributed 20 to it. Specifically the components that I would 21 have been fully responsible for would likely be 22 considerable. 23 Q. Which components were you 24 fully responsible for? Page 334 1 A. I cannot say which I have been 2 fully responsible for. I suspect in terms of 3 putting together the tables that you see at the 4 end of this document, I would have prepared with 5 the assistance of the statistician on the 6 project. Regarding the text, I suspect that I 7 was involved in the preparation of the text with 8 Doctor Masica, Doctor Dornseif. 9 Q. I'm sorry, which part of the 10 text? 11 A. I suspect the working draft 12 text. I was not fully responsible for, but would 13 have been involved to a considerable extent with 14 my colleagues on the project. 15 Q. This talks about three reviews 16 being done with regards to the violent aggressive 17 behavior analysis, correct? 18 A. That's correct. 19 Q. Okay. What was the first 20 review that was done? 21 A. The first review would have 22 been events of hostility and anti-social 23 reaction, which had been observed during the 24 premarketing evaluation of Fluoxetine. Page 335 1 Q. So these are clinical trials 2 that were performed prior to the drug being 3 marketed? 4 A. That's correct. 5 Q. What was done on that search? 6 A. As best I can ascertain, the 7 U.S. clinical trials were searched for those two 8 event terms. 9 Q. Being hostility and 10 anti-social reaction, correct? 11 A. According to this document, 12 yes. 13 Q. Was this search done before or 14 after the search of the DEN data base with the 15 seventeen event terms? 16 A. I don't recall. 17 Q. This indicates that it was 18 done before, does it not? 19 A. I don't think it specifically 20 states that. 21 Q. It says the first of three 22 reviews, correct? 23 A. I'm not sure if that refers to 24 the first of the three reviews presented in the Page 336 1 paper or whether that was the first of three 2 reviews chronologically. 3 Q. How could we find out if it 4 was the first review? 5 A. Other individuals may have a 6 sharper recollection than I would. 7 Q. You were one of the primary 8 people in charge of this project, though, Doctor, 9 weren't you? 10 A. That's correct. 11 Q. So who else would have a 12 sharper recollection of what this project was 13 about besides you? 14 A. I don't know. 15 Q. Was this review reflected in 16 your paper, this first review? 17 A. I do not believe that it was. 18 Q. Why not? 19 A. Because as best I can 20 ascertain, these events were two of the events 21 that would have been within the aggression 22 cluster that would have been applied to the 23 double-blind comparator placebo controlled data 24 base, and therefore would have been captured Page 337 1 within that, and would have -- the larger search 2 would have included both pre and post-marketing 3 events from the double-blind comparator placebo 4 controlled trials. 5 Q. Would it have been good 6 science to run this review first before running 7 the event terms listed in Exhibit 1 through the 8 DEN data base? 9 A. I'm not sure that it would 10 have made any difference in terms of how one 11 looks at it scientifically. 12 Q. It would have given you a 13 preview of what you would have found when you ran 14 the two terms, would it not? 15 A. If indeed that occurred, it 16 would have given some sense. 17 Q. Let's look at the last full 18 paragraph on that page, it starts with two 19 patients with events mapping to Lilly ELECT term 20 anti-social reaction. Do you see that? 21 A. That's correct. 22 Q. The two terms are described as 23 a shoplifting incident and increased shinus, 24 correct? Page 338 1 A. That's correct. 2 Q. In your review of the DEN 3 1639s that came out of the search of the event 4 terms listed in Exhibit 1, would you have 5 included those two event terms or those two 6 events in the analysis that you gave or the 1639s 7 that you gave to Doctor Beasley to review? 8 A. Would you repeat the question, 9 please? 10 Q. Sure. Let me ask it this way: 11 Do either of those events indicate to you either 12 verbalization or an actual act of aggression 13 towards another person? 14 A. They do not. 15 Q. So those two wouldn't have 16 ended up in the 1639s that you would have given 17 to Doctor Beasley to review after your review of 18 the 1639s that came out of the DEN search, 19 correct? 20 A. Repeat that, please. 21 Q. Sure. These two events 22 wouldn't have made it into the final eleven 1639s 23 that were used to allegedly create the aggression 24 cluster of events, correct? Page 339 1 A. They may have, it would depend 2 upon the assessment that one would make in the 3 process of establishing the methodology. 4 Q. You just said yourself that 5 you wouldn't have included them in the 1639s 6 indicating injurious behavior, right? 7 MR. MYERS: Let me object to the form, 8 that isn't what he said. 9 Q. Would you have or would you 10 not have included them in the 1639s that 11 indicate, in your opinion, injurious behavior 12 towards others? 13 A. In that analysis? 14 Q. Right. 15 A. I would have included them 16 because we did a blinded search of the data base 17 and that was established a priori. 18 Q. The DEN data base, you did a 19 blinded search? 20 A. I'm sorry, the blinded search 21 of the clinical trial. 22 Q. I'm talking about the DEN data 23 base. Yesterday we talked extensively about how 24 the event terms listed in Exhibit 1 were run Page 340 1 through the DEN data base and you reviewed the 2 1639s that were kicked out the data base as a 3 result of those searches, correct? 4 A. That's correct. 5 Q. Okay. And you reviewed those 6 1639s to make a determination as to whether or 7 not the incidents indicated either a 8 verbalization or an actual act of aggression 9 towards another person, correct? 10 A. As best I recall, yes. 11 Q. And you culled out the ones 12 that you felt clearly did not indicate a 13 verbalization or an actual act of aggression, 14 correct? 15 A. As best I recall. 16 Q. Would these have made it 17 through the first cut, your initial review? 18 A. Of these specific events? 19 Q. Yes. 20 A. They would not have. 21 Q. Okay. So would they have had 22 any impact whatsoever in and of themselves on the 23 development of the aggression cluster of events? 24 A. These two events specifically? Page 341 1 Q. Right. 2 A. No. 3 Q. Okay. 4 A. This does jog my recollection 5 to the question you asked earlier about 6 sequentially. This was done after the blinded 7 search of the data base, and the reason I know 8 that and it comes back to me is because I can 9 recall being very surprised that these two events 10 were captured -- or the benign nature of the 11 events, not that they were captured, but that 12 they were so benign. 13 Q. Under the anti-social reaction 14 that you and your colleagues felt would be most 15 likely the event term that psychiatrists would 16 use to map to violent aggressive behavior, 17 correct? 18 A. One of the event terms. 19 Q. After these came up, did you 20 reevaluated with your colleagues whether or not 21 you should run any of the other event terms 22 listed in Exhibit 1 in its place? 23 A. No, I did not. 24 Q. Why not? Page 342 1 A. Because the methodology was 2 established a priori. 3 Q. When was paranoid reaction 4 added to the aggression cluster of events -- or, 5 I'm sorry, personality disorder, when was that 6 added? 7 A. As best I recall, all events 8 that were applied to the double-blind clinical 9 trial data base were established -- were selected 10 prior to that application occurring. 11 Q. Before or after the first 12 analysis was done? 13 A. Which first analysis? 14 Q. The ones that we just talked 15 about, the first review. 16 A. The first review? 17 Q. The one that's reflected in 18 this exhibit, Doctor, that we just got done 19 talking about. Was it added before or after this 20 review, or was just hostility and anti-social 21 reaction? 22 A. As best I recall, it would 23 have been added before that review. 24 Q. Why wasn't a review of that Page 343 1 event term done with the other two? 2 A. In the first analysis? 3 Q. Right. 4 A. I don't recall. 5 MS. ZETTLER: Let's take a break. 6 (A SHORT RECESS WAS TAKEN.) 7 (PLAINTIFFS' EXHIBIT NO. 5 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Have you had a chance to 11 review Exhibit 5? 12 A. I have. 13 Q. Do you recognize this exhibit, 14 Doctor? 15 A. I do. 16 Q. Can you tell me what it is? 17 A. This is a communication in 18 which information is provided about assaultive 19 behavior that were nonfatal. 20 Q. Where was this information 21 gleaned from? 22 A. This would appear to have been 23 derived from the spontaneous post-marketing 24 reports, as well as from the clinical trials. Page 344 1 Q. Why do you say that? 2 A. There's one clinical trial 3 patient listed here. 4 Q. And that's the first one under 5 HCCD? 6 A. Yes, ma'am. 7 Q. Okay. Do you have any way of 8 knowing if that HCCD patient is one of the ones 9 that is also listed on the third page of Exhibit 10 2? 11 A. To my recollection, that 12 patient would be included in this particular -- 13 Q. The listing that's the third 14 page of Exhibit 2? 15 A. That's correct. 16 Q. What makes you say that? 17 A. Primarily I recall this 18 patient being included -- was included in the -- 19 I recall this patient being included in the 20 analysis of the double-blind clinical trial data 21 base. The comment section here sort of jogged my 22 memory relative to that. 23 Q. The comment section on the 24 first page of Exhibit 5? Page 345 1 A. Yes, ma'am. 2 Q. Where it says patient tried to 3 harm husband after argument, Fluoxetine dose 4 lower without recurrence? 5 A. That's correct. 6 Q. This patient listed as the 7 first patient on Exhibit 5, was she included in 8 the final analysis that was reported in your 9 paper? 10 A. If she was from a double-blind 11 comparator placebo controlled trial, she would 12 have been. 13 Q. But she wasn't, was she? 14 A. I don't recall if that's a 15 double-blind comparator placebo controlled trial. 16 Q. Earlier you testified that you 17 believed that the patients from HCCD were not 18 included because it was not a double-blind 19 controlled study. 20 A. That was my recollection, I'm 21 just not sure of that. 22 Q. Is it your testimony that the 23 rest of these patients listed on Exhibit 5 were 24 patients that were reported to the DEN data base Page 346 1 as spontaneous adverse events? 2 A. They would all appear to be 3 spontaneous reports. 4 Q. Could this patient that was in 5 study HCCD have been reported to the DEN data 6 base as an alert report? 7 A. It's possible. 8 Q. Yesterday you testified that 9 you weren't sure but you thought it was somewhere 10 between nine and eleven 1639s that were the 11 result of your review of the eleven hundred or so 12 1639s that were pulled because of the search of 13 the events listed in Exhibit 1. Could this be 14 the line listing that you were talking about 15 yesterday reflecting the data on those patients? 16 A. It could be. 17 Q. So Exhibit 5 could be that 18 line listing? 19 A. Could be. 20 Q. Did you put together this 21 exhibit, Exhibit 5? 22 A. To the best of my 23 recollection, yes, I would have put it together. 24 Q. Is there anything about this Page 347 1 exhibit that refreshes your recollection as to 2 whether or not this is in fact the line listing 3 that you put together as a result of your review 4 of the 1639s? 5 A. I can't be sure. 6 Q. Okay. What else might this 7 be? 8 A. It could have been, although I 9 doubt it, it could have been a listing of alert 10 reports, but I doubt that. 11 Q. Okay. Why? 12 MR. MYERS: Why does he doubt it? 13 MS. ZETTLER: Right. 14 A. I am uncertain as to whether 15 each one of these events would have been reported 16 as an alert report. 17 Q. If these had alert reports 18 would you have listed the outcome on this line 19 listing, if that was what you were putting this 20 together for, would be a review of the alert 21 reports, would you have put in an outcome? 22 A. Are you referring to the 23 comments as the outcome? 24 Q. No, an outcome as listed on Page 348 1 the 1639. 2 A. As regards -- 3 Q. To each event. 4 A. -- seriousness and expectancy, 5 is that what you're asking. 6 Q. Right. I mean that's what the 7 term is on whether or not something is an alert 8 report, right? 9 A. That is correct. 10 Q. Okay. 11 A. But I would not have included 12 that on this line listing. 13 Q. How come? 14 A. Routinely I did not, in any 15 line listing, list expectancy as best as I 16 recall. 17 Q. Okay. How about these little 18 paragraphs on each patient that makes up the last 19 few pages of Exhibit 5? 20 MR. MYERS: What about them? 21 Q. Did you write these? 22 A. I believe this is my work. 23 Q. Does this refresh your 24 recollection as to whether or not this exhibit Page 349 1 reflects a discussion of 1639s that resulted from 2 your analysis of the DEN data base? 3 A. This does not refresh my 4 memory. 5 Q. Do you know if you did -- 6 wrote such paragraphs for all of the patients 7 that were pulled or flagged because of your 8 searches of the clinical trial data base? 9 A. I do not recall. 10 Q. Was there a time when you and 11 your colleagues considered publishing the violent 12 aggression paper as part of a suicide analysis 13 done by Doctor Beasley? 14 A. Not that I recall. 15 (PLAINTIFFS' EXHIBIT NO. 6 WAS 16 MARKED FOR IDENTIFICATION AND 17 RECEIVED IN EVIDENCE.) 18 Q. Have you had a chance to 19 review Exhibit 6? 20 A. Yes, ma'am. 21 Q. Does that refresh your 22 recollection as to whether or not the reports 23 were ever going to be published together as one 24 article? Page 350 1 MR. MYERS: Let me just ask, when you 2 say the reports, do you mean the aggression paper 3 we've been talking about, obviously, and the 4 paper that Doctor Beasley and others ultimately 5 published in the British Medical Journal? 6 MS. ZETTLER: Right. 7 MR. MYERS: Okay. 8 A. I do not recall there was any 9 discussion prior to the publication of the lead 10 manuscript, the lead articles, relative to 11 publishing them as a single article. 12 Q. How about afterwards? 13 A. This would have occurred 14 later, yes. 15 Q. Okay. Do you recall 16 discussions of publishing an article called 17 "Fluoxetine Not Associated With Increased 18 Suicidality Or Aggression In Controlled Clinical 19 Trials"? 20 A. I do. 21 Q. Okay. Tell me about that. 22 A. Frequently an article is 23 published in a more abbreviated format, in 24 addition to a lead article, and there was a Page 351 1 request to publish this particular article in an 2 abbreviated format. 3 Q. Okay. The information that 4 was to be published in the article that is 5 reflected in Exhibit 6, would that have been 6 information from Doctor Beasley's meta-analysis 7 article as well as your article, your violent 8 aggression article? 9 A. As best I recall. 10 Q. Would any additional 11 information be included in that article as 12 reflected by Exhibit 6, other than information 13 from those two papers? 14 A. I do not recall that there 15 would have been additional information. 16 Q. Was this article submitted to 17 the International Clinical Psychopharmacology? 18 A. Yes, ma'am. 19 Q. Was it published? 20 A. I believe that it was. 21 Q. When? 22 A. It was submitted in 1993, I 23 believe it was published the same year. 24 Q. Do you remember when in 1993? Page 352 1 A. No, I don't. 2 Q. Who is Mario Fava? 3 A. Doctor Fava is a researcher at 4 Massachusetts General Hospital. 5 Q. How about Gerald Rosenbaum? 6 A. The same. 7 Q. Is a researcher at 8 Massachusetts General Hospital? 9 A. That's correct. 10 (DISCUSSION OFF THE RECORD.) 11 Q. Do you know Doctor Rosenbaum 12 and Doctor Fava? 13 A. I do. 14 Q. How do you know them? 15 A. I know them by their 16 reputation and I know -- I've had interactions 17 with Doctor Rosenbaum over the last, I would say, 18 four years. 19 Q. I'm sorry, you have had what 20 with him? 21 A. Some interactions with Doctor 22 Rosenbaum. 23 Q. In what context did you have 24 interactions with him? Page 353 1 A. As I best recall, Doctor 2 Rosenbaum was one of the consultants that Lilly 3 engaged in the effort to analyze the clinical 4 trial data base regarding suicidality. 5 Q. Okay. 6 A. In addition, I've had 7 interactions with Doctor Rosenbaum at select 8 national meetings. And he's been a visitor at 9 Lilly on at least one occasion. 10 Q. A visitor at Lilly, is that 11 what you said? 12 A. Yes. 13 Q. When was that additional 14 occasion that he was a visitor at Lilly? 15 A. As best I recollect, it was 16 maybe two months ago. 17 Q. What was the occasion of him 18 visiting Lilly two months ago? 19 A. As best I recollect, he was 20 here to discuss a study with one of my 21 colleagues. 22 Q. What study, Fluoxetine study? 23 A. As best I recall, it was a 24 Fluoxetine study. Page 354 1 Q. A Fluoxetine study that he is 2 conducting or was conducting? 3 A. As best I recall, it's a study 4 that he plans to do. 5 Q. Depression study? 6 A. As best I recall, it's in the 7 depressed population, yes. 8 Q. What is that study about? 9 A. I don't recall. 10 Q. Does it have anything to do 11 with suicidal ideation and the use of Fluoxetine? 12 A. Not that I recall. 13 Q. Does it have anything to do 14 with violent aggressive behavior and the use of 15 Fluoxetine? 16 A. Not that I recall. 17 Q. Who was the colleague that he 18 was meeting with about the study? 19 A. Doctor Pande. 20 Q. When did Doctor Rosenbaum 21 first become a consultant to Lilly on the 22 suicidality issue? 23 A. As best I recollect, it would 24 have been somewhere mid-year, 1990. Page 355 1 Q. Do you know why Doctor 2 Rosenbaum was asked to become a consultant on the 3 suicidality issue? 4 A. I don't know. 5 Q. Do you know if Doctor 6 Rosenbaum has ever written an article critical of 7 Fluoxetine in any way? 8 A. I don't know. 9 Q. How often have the consultants 10 been to Lilly on a suicidality issue as far as 11 you know? 12 A. I don't recall. 13 Q. More than once? 14 A. Possibly. 15 Q. More than five times? 16 A. I don't believe so. 17 Q. Was there a meeting of all the 18 consultants at the same time that you recall? 19 A. As best I recall, there was a 20 consultant group that was identified that did 21 meet. There may have been other consultants 22 engaged at various times. 23 Q. List for me the people in the 24 consultant group. Page 356 1 A. As best I recollect? 2 Q. Yes. 3 A. Doctor Rosenbaum, Doctor 4 Fawcett. 5 MR. SMITH: Beg your pardon? 6 THE WITNESS: Doctor Fawcett. 7 Q. Okay. 8 A. Doctor Tollefson, and Doctor -- 9 I believe Doctor Winokur, W-I-N-O-K-U-R. 10 Q. Anybody else? 11 A. I don't recall others that 12 were part of that initial group. 13 Q. Is this group different than 14 the psychiatric advisory panel? 15 A. Yes, ma'am. 16 Q. Any members of this group that 17 were also on the psychiatric advisory panel? 18 A. As best I recollect, the only 19 person who might have been a member of both would 20 have been Doctor Fawcett. 21 Q. How about David Dunner, was he 22 in the consultant group? 23 A. Not that I recall. 24 Q. Did you ever attend any of the Page 357 1 meetings of the consultant group? 2 A. I recall attending a meeting. 3 Q. When was that meeting? 4 A. I believe that was the meeting 5 that was mid-year, 1990. 6 Q. Had the group been formed 7 before that? 8 A. Is the question had they met 9 before that? 10 Q. No, had the group been 11 together or -- yes, I guess so, met. 12 A. Not that I'm aware of. 13 Q. When was the group formed? 14 A. As best I recollect -- I don't 15 know. 16 Q. Was it before or after Doctor 17 Teicher's article came out in January of '90? 18 A. As best I recollect, it would 19 have been after. 20 Q. How long was the meeting of 21 the consultant group that you attended? 22 A. As best I recollect, it was 23 somewhere between a half and a full day. 24 Q. Who from Lilly attended that Page 358 1 meeting besides you? 2 A. I recall Doctor Beasley. I 3 don't recall the others. 4 Q. Doctor Wheadon? 5 A. He may have been there. 6 Q. Doctor Kotsanos? 7 A. I don't know. 8 Q. Doctor Street? 9 A. I don't recall. 10 Q. Doctor Leigh Thompson? 11 A. I don't recall. 12 Q. Anybody from marketing? 13 A. I don't recall. 14 Q. Anybody from upper management? 15 A. Could you define upper 16 management? 17 Q. Like vice-presidents, chairmen 18 of the boards, CEO? 19 A. I don't recall. 20 Q. How about Max Talbott, was he 21 there? 22 A. I don't know. 23 Q. How about Doctor Wernicke? 24 A. I don't recall. Page 359 1 Q. Any statisticians? 2 A. Very likely there would have 3 been statisticians. 4 Q. How about Doctor Dornseif? 5 A. Possibly. 6 Q. Do you have any specific 7 recollection either way if he was there or not? 8 A. I don't. 9 Q. Tell me what was discussed 10 during that first meeting. 11 A. I do not recall the specifics, 12 of course, in their entirety. 13 Q. Tell me what you do remember. 14 A. I do recall there was some 15 discussion of how one could address the data base 16 as regards the issue of suicidality. 17 Q. Anything else? 18 A. I recall that Doctor Beasley 19 made some presentations. 20 Q. Presentations regarding what? 21 A. I don't recall. 22 Q. Anything else that you do 23 recall? 24 A. I do recall that there was a Page 360 1 great deal of discussion and suggestions that 2 came from this group. 3 Q. What discussions did Doctor 4 Fawcett -- or what suggestions did Doctor Fawcett 5 make? 6 A. I don't recall. 7 Q. Do you recall any of the 8 suggestions that any of the consultants made 9 during that meeting? 10 A. Yes, I do. 11 Q. Tell me what suggestions you 12 recall and if you remember, who made those 13 suggestions. 14 A. Yes. As I recall there was a 15 suggestion made that the best way to approach the 16 question of suicidality with the information at 17 hand would be to embark upon an item three 18 analysis. That is the Hamilton item that looks 19 at suicidal ideation. I recall that suggestion 20 came from Doctor Tollefson, and I recall that 21 there was considerable support for that analysis, 22 and specifically from others gathered, as well as 23 Doctor Tollefson, discussion about the baseline 24 to end point change, a look at the data of Page 361 1 patients who had a score of zero or one at 2 baseline to a high score at the end, and patients 3 who had a high score, as I recall, at the 4 beginning, what happened to those individuals 5 over time. 6 Q. Anything else? 7 A. As best I recall -- I mean as 8 best I recall, that's what I recall, I'm sorry. 9 Q. Do you agree with Doctor 10 Tollefson's suggestion about analyzing the 11 HamD-3? 12 A. Yes, I do. 13 Q. Why? 14 A. I think that it is, in my 15 estimation, it's the best approach that one had 16 from the existing data base from the double-blind 17 clinical trials to address the question in an 18 unbiased fashion. 19 Q. In fact the Hamilton 20 Depression Rating, question three, was the only 21 indicator of suicidality that was included in the 22 clinical trials, correct? There were no other 23 scales that were involved that were directly 24 related to suicidal ideation, were there? Page 362 1 A. Across all trials, that's as 2 best I recall. 3 Q. Was there anything else you 4 could have looked at from the information during 5 the clinical trials that would have been an 6 indicator of suicidal ideation? 7 A. As best I recollect, from the 8 data that was gathered, that would have been the 9 most uniform. 10 Q. Were the consultants concerned 11 that serious suicidal risk was an exclusion 12 criteria in many if not most of the trials? 13 A. I don't believe that they were 14 concerned. 15 Q. Were you aware that Doctor 16 Fawcett had published a paper and in fact 17 presented a paper around the same time period at 18 a psychiatric conference in which he recommends 19 giving sedatives or benzodiazepines to Fluoxetine 20 users who present a serious suicidal risk? 21 A. I don't recall that. 22 Q. Did he raise that at the 23 meeting? 24 A. I do not recall that he did. Page 363 1 Q. Has he ever discussed that 2 with you? 3 A. Not to my recollection. 4 Q. Was the stimulant properties 5 of Fluoxetine raised as an issue during this 6 meeting? 7 MR. MYERS: Wait a minute. Before he 8 answers, let me object to the form. You used the 9 term stimulant properties. 10 A. In my estimation, Fluoxetine 11 does not have stimulant properties. 12 Q. I'm not asking for your 13 estimatation, I'm asking you if the issue was 14 raised during this meeting of the consultants? 15 MR. MYERS: Did somebody say that? 16 MS. ZETTLER: If the issue was raised 17 in any way. 18 MR. MYERS: I object to the form. If 19 you know, tell her. 20 A. I don't recall. 21 Q. Was the issue of the German 22 government's questioning of whether or not 23 Fluoxetine causes suicidal ideation or increases 24 suicidal ideation raised at the meeting? Page 364 1 MR. MYERS: Wait a minute. Before he 2 answers, let me just object to the form because I 3 think you mischaracterized what the question was. 4 But if you know, tell her. 5 A. I don't recall. 6 Q. Are you aware that the BGA, 7 the German counterpart to the FDA, had raised 8 that issue back in 1984? 9 MR. MYERS: Same objection. If you 10 know, tell her. 11 A. As best I recall, that was not 12 the question. 13 Q. What was the question? 14 A. I don't recall. 15 Q. There was a question regarding 16 Fluoxetine and suicidality from the BGA, was 17 there not? 18 MR. MYERS: When, since you cited a 19 couple of dates, at what point in time? 20 MS. ZETTLER: Back in '84. 21 MR. MYERS: Go ahead. 22 MR. SMITH: Need some help, Doctor, 23 from your counsel? 24 MR. MYERS: Paul, be quiet. Page 365 1 MR. SMITH: I want the record to 2 reflect that the witness is looking at the 3 attorney for Lilly seeking some assistance, 4 apparently. 5 MR. MYERS: That's your 6 characterization, Mister Smith. Answer the 7 question, Doctor Heiligenstein. 8 A. Would you repeat the question, 9 please? 10 MS. ZETTLER: Would you read it back? 11 (THE COURT REPORTER READ BACK THE 12 REQUESTED TESTIMONY.) 13 A. I do not recall the question 14 that was asked. 15 Q. Do you recall that in 1986, a 16 review of the clinical trial data base that was 17 available then was done in order to respond to 18 questions by the BGA on suicidal ideation and the 19 use of Fluoxetine? 20 A. I have a vague recollection of 21 the BGA making several requests. 22 Q. Do you recall that an analysis 23 of the data base, clinical trial data base, was 24 performed by Lilly in response to a question by Page 366 1 the BGA with regards to suicidality and the use 2 of Fluoxetine, Doctor? 3 A. I do not recall that that was 4 a specific question. I recall there was some 5 question that the BGA authorities requested. 6 Q. Suicidality information? 7 A. As best I recall, yes. 8 Q. Was that fact brought to the 9 attention of the consultants? 10 A. I don't recall. 11 Q. Was that analysis provided to 12 the consultants? 13 A. I don't recall. 14 Q. Was there any written material 15 provided to the consultants prior to the meeting 16 that you attended? 17 A. I don't recall. 18 Q. How would we find out whether 19 or not there was material given to the 20 consultants? 21 A. I suppose the best person to 22 ask would be Doctor Beasley. 23 Q. As a result of the German 24 government's request for an analysis of the Page 367 1 clinical trial data base regarding suicidality 2 and the use of Fluoxetine, were the clinical 3 trials that were performed after that time 4 altered in any way to look more closely at the 5 issue of suicidality and the use of Fluoxetine? 6 MR. MYERS: After the question or 7 after the response? 8 MS. ZETTLER: Either one. 9 A. I don't recall. 10 Q. Were other scales added to the 11 clinical trials after 1986 regarding suicidality 12 prior to the FDA's request that the Adult 13 Suicidal Ideation Questionnaire be added? 14 A. Not that I recall. 15 MS. ZETTLER: Larry, I'm going to turn 16 this over to Paul because my voice is really 17 starting to go. I may have some questions later, 18 I don't know if I do or not at this point. 19 MR. MYERS: Okay. 20 * * * * * * * * * * 21 EXAMINATION 22 BY MR. SMITH: 23 Q. Doctor Heiligenstein, my name 24 is Paul Smith, and I would like for you to Page 368 1 observe the same rules in connection with my 2 questions that you did with Ms. Zettler, in that 3 if you do not understand a question I ask, will 4 you please let me know and I will rephrase that 5 question? 6 A. Yes, sir. 7 Q. And if you answer a question 8 that I ask, I'm going to assume that you 9 understood that question, okay? 10 A. Yes, sir. 11 Q. In connection with your 12 clinical practice that you engaged in for a short 13 period of time, do I understand it that you saw 14 private practice -- patients in private practice 15 from 1982 until 1986? 16 A. That's incorrect. 17 Q. All right. Tell me when you 18 had an office and saw private patients where you 19 would charge them a fee, like if I had a 20 psychiatric problem and looked in the Yellow 21 Pages or something? 22 A. I had an office throughout my 23 training in which I saw patients who were charged 24 a fee. I had an office while on the faculty at Page 369 1 the Medical University of South Carolina, during 2 which time I saw patients and charged a fee. And 3 I had an office subsequent to my leaving MUSC 4 full-time and moving into a blended type of 5 practice, private practice, and some teaching for 6 an additional approximately five and a half years 7 thereafter. 8 Q. And that was in Greensboro, 9 South Carolina or North Carolina, where was it? 10 A. That was in Greensboro, North 11 Carolina, Charleston, South Carolina, and Park 12 Ridge, Illinois. 13 Q. Why did you move around so 14 much during that period of time? 15 MR. MYERS: I object to the form only 16 because of that period of time. I'm not 17 suggesting you weren't paying attention 18 yesterday, Paul, but it was not a short period of 19 time. Go ahead and tell him why you moved. 20 A. I left the Medical University 21 to move into a private practice opportunity. 22 Q. Where was that private 23 practice opportunity? 24 A. Greensboro, North Carolina. Page 370 1 Q. Okay. Did you have an office 2 there? 3 A. Yes, sir. 4 Q. And did it say Doctor 5 Heiligenstein, Psychiatrist, were you practicing 6 psychiatry at that time? 7 A. Yes, sir. 8 Q. Okay. 9 A. And I had an office, I don't 10 know that our names were on the door. 11 Q. How would people know you were 12 there if you didn't have your names on the door? 13 A. I made presentations at 14 various medical meetings locally, and served as a 15 referral source for a number of pediatricians in 16 the greater Greensboro community as well as 17 derived referrals from the hospital in which I 18 was a director of the adolescent inpatient unit. 19 Q. Did you have an address there 20 where that office was? 21 A. Yes, sir. 22 Q. What was that address? 23 A. I do not recall the specific 24 address, it was on North Elam, E-L-A-M, Street or Page 371 1 Avenue. 2 Q. In Greensboro, North Carolina? 3 A. Yes, sir. 4 Q. Give me the years that you 5 were there on North Elam Street? 6 A. As best I recall, 1982 and 7 part of 1983. 8 Q. When in 1982 and until when in 9 1983? 10 A. I cannot remember the exact 11 date I moved into the office, it would have been 12 sometime after February of 1982. And I returned 13 to Charleston, I believe, in August of 1983. 14 Q. So you were on North Elam 15 Street until approximately August, 1983? 16 A. That's correct. 17 Q. How many days -- how many 18 patients a day were you seeing at that address? 19 A. I do not recall. 20 Q. Approximately? 21 A. My best estimate would be 22 approximately five. 23 Q. How many days a week did you 24 see patients there? Page 372 1 A. Five or six. 2 Q. Were these patients who were 3 there for treatment of psychiatric disorders? 4 A. Yes, sir. 5 Q. Any particular psychiatric 6 disorder that you were specializing in at that 7 time? 8 A. My interests and areas of work 9 are broad. I had a special interest in children 10 and adolescents who had difficulties within their 11 family. I had a special interest in attention 12 deficit hyperactivity disorders. I had a special 13 interest in affective disorders of children and 14 adolescents, and I had a special interest in 15 anxiety spectrum disorders of children and 16 adolescents. 17 Q. Were the majority of your 18 patients children during that time at that 19 location? 20 A. I would say that a slight 21 majority were adolescents. 22 Q. Fifty-five percent were 23 adolescents? 24 A. Possibly. Page 373 1 Q. Is that your best estimate? 2 A. Yes, sir. 3 Q. So the other forty-five 4 percent would have been adults? 5 A. I'm sorry. I would have had a 6 small percentage of my outpatients at that time 7 who would have been adults whom I would have been 8 seeing individually. These would have been 9 primarily young adults, twenty and above. The 10 largest single group, if I split children from 11 adolescents, would have been the adolescent 12 population, with slightly fewer children. 13 Q. Okay. So you saw a large -- a 14 greater percentage of adolescents. Then next in 15 percentage would be children, correct? 16 A. Yes, sir. 17 Q. Then you saw a small 18 percentage of adults? 19 A. That's correct. 20 Q. So the majority of the people 21 that you were treating were young people? 22 A. That's correct. 23 Q. Below the ages of twenty-five? 24 A. Yes, sir. Page 374 1 Q. What percentage of those 2 patients at that time were below the age of 3 twenty-five? 4 A. In terms of the use in 5 prescribing of medication? 6 Q. No, in terms of the people 7 that you saw back for that period of time at the 8 Elam address. 9 A. As best I recall, every child 10 and adolescent I saw, I also saw in the context 11 of their family. Now there are those who would 12 say that is a treatment intervention when one 13 engages the family, and that's why I'm making 14 that distinction. So that I would have seen a 15 very sizeable number of parents, step-parents of 16 these younger people that I was treating on -- 17 quite often on a regular basis. And I would then -- 18 Q. But they were not the 19 individuals making the complaints, were they? 20 MR. MYERS: Go ahead and finish your 21 answer, Doctor. 22 A. They may not have been the 23 identified patient, but I would have been 24 treating the family on some of those occasions as Page 375 1 well as the child. 2 Q. Would you charge the child and 3 the parents separate fees? 4 A. No, sir. As best I recall, it 5 was billed under the child. 6 Q. That's what I'm interested in. 7 What was your work in connection with children 8 versus adults? I know that children have to have 9 adult parents, and that a lot of the problems 10 that the child presents with are family problems, 11 but I want to distinguish out your practice at 12 that time in dealing with disorders created or 13 manifested by the children versus seeing an adult 14 patient for an independent psychiatric disorder. 15 A. As best I understand that 16 question, in my practice, at that time, I would 17 estimate that ninety percent plus of the patients 18 who I treated as the identified patient would 19 have been in that younger age group. 20 Q. And the other ten percent 21 would be adults? 22 A. That's correct. 23 Q. Of those ninety percent of 24 children, at that time, how many suffered from Page 376 1 the psychiatric disorder known as depression? 2 A. My best estimate would be 3 approximately a third. 4 Q. And of those ten percent less 5 of adults that you saw for separate psychiatric 6 disorders, what percentage of those patients were 7 suffering from depression as the psychiatric 8 disorder that you were treating? 9 A. As best I recollect, 10 approximately fifty percent. 11 Q. Fifty percent of the ten 12 percent? 13 A. Yes, sir. 14 Q. Which would be five percent of 15 your total population were adults who were being 16 treated for depression at that time? 17 A. In my outpatient practice, 18 yes. 19 Q. Yes. Is that correct? 20 A. That's correct, sir. 21 Q. Over those years that you have 22 practiced psychiatry in a private practice 23 setting where you charged the patient a fee for a 24 consultation or a fee for evaluation and Page 377 1 treatment, what percentage of those patients were 2 suffering as the primary diagnosis depression? 3 A. I would estimate forty to 4 fifty percent. 5 Q. And that would be including 6 children and adults? 7 A. Yes, sir. 8 Q. And of those patients, how 9 many patients were being treated by you with the 10 assistance of psychopharmacological medication? 11 MR. MYERS: Of the depressed patients? 12 MR. SMITH: I said of those patients. 13 A. Are you referring to the 14 depressed patients, sir? 15 Q. Of course. 16 A. I would estimate ninety 17 percent plus. 18 Q. Why? 19 A. Because in my assessments, I 20 would have judged those individuals to be of the 21 type of depression that would -- that they would 22 benefit from treatment with an antidepressant. 23 Q. In other words it was your 24 judgment, at the time, that ninety percent plus Page 378 1 of the depressed individuals that you were 2 treating were suffering depression, at least in 3 part based on a physiological condition that 4 could be treated with medications, is that right? 5 A. Yes, sir. 6 Q. You are of the opinion that 7 depression has a biological, physiological 8 component, are you not? 9 A. I'm of the opinion that in my 10 referral population, a significant number of the 11 individuals so referred or self-referred did 12 indeed suffer from an endogenous or biological 13 depression. 14 Q. In other words there was 15 something in those patients that caused them to 16 be depressed that was within their body, that was 17 based on some physiological, either abnormality 18 or derangement or imbalance, for lack of better 19 terms? 20 A. That is a theoretical 21 construct. 22 Q. I'm not asking you about 23 theory, I'm asking you about what you believe in 24 connection with the patients that you treated. Page 379 1 A. In my estimation, for those 2 patients that I so treated, I felt there was a 3 high likelihood that those individuals may very 4 well have some sort of physiological or 5 biological component to their illness. 6 Q. And those individuals who are 7 depressed, suffering from this physiological and 8 biological component, did not suffer in your 9 judgment a weakness, as that term is felt and 10 used by the lay people? 11 MR. MYERS: Before he answers, let me 12 object to the form in the use of that term as 13 being awfully vague and undefined. But if you 14 can answer, go ahead. 15 A. I would ask for a 16 clarification of weakness. 17 Q. A weakness or a defect in 18 character. 19 A. Thank you. I do not think 20 that those individuals were suffering from a 21 weakness or defect in character that resulted in 22 their depression. 23 Q. And these people were 24 physically, physiologically ill? Page 380 1 A. In my best estimation, yes. 2 Q. And is that your judgment with 3 respect to the general depressed population that 4 are being treated with antidepressant medication, 5 that those individuals have a physiologic, 6 biologic component to their illness? 7 A. Yes. 8 Q. And that Prozac, being an 9 antidepressant, in your judgment causes a 10 physiologic, biologic reaction in individuals? 11 A. Fluoxetine does have an impact 12 on central nervous system functioning. 13 Q. It does affect individuals' 14 central nervous system, doesn't it? 15 A. That's correct. 16 Q. And you, being trained in 17 neurology, as well as psychiatry, are familiar 18 with the serotonin system and the basic concept 19 of how Fluoxetine inhibits the reuptake of 20 serotonin? 21 A. Yes. 22 Q. And that is a biologic 23 process, is it not, Doctor? 24 A. That's correct. Page 381 1 Q. If I took Prozac, it would 2 have some biologic effect on me, wouldn't it? 3 A. It should. 4 Q. Whether I'm depressed or not, 5 shouldn't it? 6 A. It should. 7 Q. In other words, Prozac just 8 doesn't work biologically on only depressed 9 people, does it? 10 A. That's correct. 11 Q. It works biologically on 12 everybody that ingests it, doesn't it? 13 A. I don't know that I can say 14 that absolutely, but I think that in the vast 15 majority of individuals who take a medication 16 such as Fluoxetine there would be a biological 17 impact. 18 Q. There is a chemical reaction 19 by virtue of these individuals ingesting this 20 drug? 21 A. I don't know that I would 22 characterize it as a chemical reaction. I would 23 characterize it as an inhibition of uptake, which 24 allows for increased function of the serotonergic Page 382 1 system. 2 Q. And these are -- serotonin is 3 a chemical, is it not? 4 A. That's correct. 5 Q. Prozac is a chemical? 6 A. That's correct. 7 Q. And this chemical, Prozac, 8 causes this chemical we have in our brain to be 9 affected, does it not? 10 A. That's correct. 11 Q. And that causes some effect in 12 all humans, doesn't it, or a ninety-nine point 13 nine percent of humans? 14 A. In my best estimate, yes. 15 Q. And in your opinion as an 16 individual who is a psychiatrist and who has 17 trained and studied also in neurology, correct? 18 A. Understand that my training in 19 neurology was limited to a single year, and I am 20 neither certified nor eligible for certification 21 in neurology. 22 Q. But you certainly feel 23 comfortable in having some knowledge of the 24 serotonin system and the biological effects of Page 383 1 the serotonin system, don't you? 2 A. Oh, yes, sir. 3 Q. And your training in neurology 4 gave you additional information in regard to the 5 serotonin system, didn't it, or did you not get 6 that far? 7 A. I don't recall that there was 8 a great deal of discussion of serotonergic 9 function or that even a great deal was known at 10 the time I did my training. 11 Q. When was that, 19 -- 12 A. '73, '74, one year. 13 Q. We've made great strides in 14 that twenty-year period, have we not, in our 15 knowledge of the serotonergic system, haven't we? 16 A. Yes, sir. 17 Q. And we've got a long way to 18 go, too, don't we, in our knowledge of the 19 serotonergic system, don't we, Doctor? 20 A. We have a long way to go in 21 overall function of the central nervous system, 22 including serotonergic. 23 Q. Including the serotonergic 24 system? Page 384 1 A. Yes, sir. 2 Q. Other drugs that will affect 3 the serotonergic system -- there are several 4 other drugs that will affect the serotonergic 5 system, aren't there? 6 A. Yes, sir. 7 Q. Cocaine affects the 8 serotonergic system, doesn't it? 9 A. I don't know that. 10 Q. You don't know that? 11 A. As a fact, I do not know that. 12 Q. Have you ever read any 13 material indicative that cocaine is a serotonin 14 reuptake inhibitor? 15 A. I do not recall reading that 16 information. 17 Q. Would you be surprised to know 18 that? 19 A. Not necessarily. 20 Q. Why? 21 A. In a sense, there are many 22 chemical entities that can impact on a specific 23 neurochemical pathway, and there are only so many 24 specific neurochemicals within the central Page 385 1 nervous system that we have identified at this 2 point in time. 3 Q. Doctor, my question is, 4 though, did you know that cocaine is a reuptake 5 inhibitor of serotonin -- 6 MR. MYERS: I object to the form. 7 Q. -- like Fluoxetine is an 8 inhibitor of a -- reuptake inhibitor? 9 MR. MYERS: I object to the form of 10 the question. If you know, tell him, Doctor. 11 A. I'm not aware that -- I'm not 12 aware of the former, and if there was uptake 13 inhibition with cocaine, that doesn't necessarily 14 mean it would be like Fluoxetine. 15 Q. Well, I mean, it is like 16 Fluoxetine in that it inhibits uptake of 17 serotonin? 18 MR. MYERS: Same objection. Tell him 19 if you know. 20 A. I don't know that that's a 21 fact. 22 Q. Well, let me ask you this 23 then: Did you know that methadone is a serotonin 24 reuptake inhibitor? Page 386 1 A. No, I did not. 2 Q. Do you know of any other drugs 3 that are serotonin reuptake inhibitors? 4 A. Yes. 5 Q. Give me one. 6 A. Peroxetine. 7 Q. Peroxetine. What is 8 Peroxetine? 9 A. It's an antidepressant. 10 Q. That's an antidepressant 11 manufactured by a competitor of your employer, is 12 it not? 13 A. That's correct. 14 Q. Do you know of any other drugs 15 that are not known as antidepressant medications 16 that are serotonin reuptake inhibitors? 17 A. Where that is a primary 18 mechanism of action, I'm not aware. 19 Q. Or any mechanism of action. 20 I'm not talking about necessarily a specific 21 serotonin reuptake inhibitor, but a medication or 22 a drug that inhibits uptake of serotonin, either 23 directly or indirectly? 24 A. I don't recall that there are Page 387 1 any. 2 Q. When you came back to Lilly in 3 1988, what was your job title? 4 A. As I recollect, it was 5 assistant clinical research physician. 6 Q. And how long did you continue 7 in that capacity? 8 A. As best I recollect, two 9 years. 10 Q. Until 1990? 11 A. As best I recollect, yes. 12 Q. And then what did you become 13 at that time? 14 A. Clinical research physician. 15 Q. How long -- are you still 16 classified as a clinical research physician? 17 A. I'm not. 18 Q. What is your -- what was your 19 next job change? 20 A. January of this year, 1994, 21 senior clinical research physician. 22 Q. What do you have to do to move 23 from assistant clinical research physician to 24 clinical research physician? Page 388 1 A. I'm not sure what those 2 criteria are. I have an idea. 3 Q. Tell me what your idea is 4 then. 5 A. My best idea is that one needs 6 to be identified as somebody who is contributing 7 in the design and implementation of studies in 8 safety monitoring of compounds, active in the 9 development of a new compound. Those sorts of 10 activities. 11 Q. How long were you -- who was 12 your supervisor while you were an assistant 13 clinical research physician? 14 A. Before or after I came back to 15 Lilly? 16 Q. After you came back to Lilly. 17 A. Doctor Dan Masica. 18 Q. And did he continue to be your 19 supervisor throughout your tenure as assistant 20 clinical research physician? 21 A. No, sir. 22 Q. Who else supervised you in 23 that position then? 24 A. He may have been. Page 389 1 Q. All right. 2 A. I can't recall specifically 3 when the new director came or when I reported to 4 a new director when that job title changed. 5 Q. Who was your supervisor when 6 you were a clinical research physician? 7 A. Doctor Masica may have been 8 for part of that time, Doctor Frederico Dies, 9 D-I-E-S, and Doctor Gary Tollefson. 10 Q. What was Doctor Dies' job 11 title? 12 A. I believe he was a director of 13 the division of neuropharmacology. 14 Q. And Doctor Tollefson? 15 A. Doctor Tollefson is an 16 executive director, at that time, I believe, of 17 the division of psychopharmacology. 18 Q. Did you have any other 19 supervisors while you were a clinical research 20 physician at Lilly? 21 A. Are you referring to immediate 22 line management? 23 Q. Yes. 24 A. Subsequent to my return, those Page 390 1 are the individuals who I reported to. 2 Q. Since you've been -- well, I 3 was only interested in while you were a clinical 4 research physician, in the capacity job title of 5 clinical research physician. 6 A. Oh, I'm sorry, I didn't 7 understand. 8 Q. I'm trying to move through 9 chronologically, and specifically be the period 10 of time between 1990 and January of 1994, when 11 you were made senior clinical research physician. 12 A. Those would be the three 13 individuals. 14 Q. All right. Who is your 15 supervisor now? 16 A. Doctor Tollefson. 17 Q. Since your return to Lilly 18 between the time, May, 1988 and up until the time 19 in 1990 that you became a clinical research 20 physician, what percentage of your time was 21 devoted to Prozac? 22 A. I would estimate ninety 23 percent. 24 Q. From 1990 until January, 1994, Page 391 1 during your tenure as a clinical research 2 physician, what percentage of your time was 3 devoted to Prozac? 4 A. That would have varied over 5 time and ranged from twenty percent to ninety 6 percent. 7 Q. When would it have been twenty 8 percent? 9 A. Currently it's twenty percent 10 or less, I would say. 11 Q. When would it have been ninety 12 percent? 13 A. From 1990 until -- I can't 14 recall when the changes would have occurred. 15 Q. What changes? 16 A. Where I took on additional 17 responsibilities for new compounds. 18 Q. Okay. See, I don't know when 19 that was, so you'll have to tell me. 20 A. I don't recall specifically 21 either. I think those responsibilities began, 22 most likely, as best I recall, began in '91, and 23 increased thereafter on sort of a gradual and 24 ongoing basis. Page 392 1 Q. Okay. In '92, what percent of 2 your time was devoted to Prozac? 3 A. My best guesstimate, as an 4 average, would be between fifty and sixty 5 percent. 6 Q. '93? 7 A. Approximately fifty percent. 8 Q. Then beginning in '94, I think 9 you said currently you're down to twenty percent. 10 So has it gone down from fifty to twenty percent 11 in these last three months, four months? 12 A. No, sir. What has occurred 13 has been a gradual decrease over time. As 14 additional studies with new clinical entities 15 have been embarked upon, and as my Prozac studies 16 came to fruition, and manuscripts were written, 17 my efforts relative to Prozac have focused on a 18 few select studies and preparation of 19 manuscripts, and some safety monitoring. 20 Q. On all the other compounds, 21 without describing to me what those compounds 22 are, those compounds that are under investigation -- 23 A. Yes, sir. 24 Q. -- that you're working on, Page 393 1 apparently now make up maybe eighty percent of 2 your time. Are those compounds all 3 antidepressant compounds? 4 A. Yes, sir. 5 Q. Are any of those compounds 6 specific serotonin reuptake inhibitors? 7 A. Can you define for me 8 "specific"? 9 Q. You don't know what the term 10 "specific serotonin reuptake inhibitor" is, 11 Doctor? 12 A. I have a definition, but I'm 13 not sure what your definition is. 14 Q. Give me what your definition 15 is. 16 A. My definition would be where 17 the primary mechanism of action is selective 18 blockage of reuptake of serotonin. 19 Q. That's my definition, too. 20 A. Okay. In response to that, 21 no, sir. 22 Q. They are -- are they 23 tricyclics? 24 A. No, sir. Page 394 1 Q. Are they MAOs? 2 A. No, sir. 3 Q. Are they combinations of any 4 of the three classically known types of 5 antidepressants? 6 MR. MYERS: Don't answer that. You 7 have gone far enough on other compounds, Paul, 8 I'm not going to let him go into that. 9 Q. But they are all 10 antidepressants? 11 A. They are targeted for 12 depression. 13 Q. But the manner in which they 14 work is different from the manner in which Prozac 15 works? 16 A. To some extent, yes. 17 Q. Well, do any of the new 18 compounds that you're investigating affect the 19 serotonin system, either directly or indirectly? 20 A. Yes, sir. 21 Q. Directly? 22 A. Yes, sir. 23 Q. And indirectly? 24 A. It's hard to know. We have Page 395 1 insufficient knowledge to know all of the 2 indirect effects a compound may have on other 3 neurotransmitter systems, so it would be 4 speculation. 5 MR. SMITH: Let's go eat. 6 (A SHORT LUNCH RECESS WAS TAKEN.) 7 Q. Doctor, in connection with 8 your study and research and analysis of the issue 9 of aggression and violence in connection with 10 Prozac, as I understand it the impetus you told 11 us yesterday to do this analysis was the 12 Wesbecker situation, is that correct? 13 A. Yes, sir. 14 Q. And in the Wesbecker matter, a 15 gentleman who was on Prozac went into his 16 employer's plant, printing plant, killed seven 17 people and injured approximately twenty others. 18 Is that your understanding? 19 A. As I recollect, he was not 20 taking Prozac at the time of the incident. But 21 in terms of the description of the actual 22 incident itself, in terms of the exact numbers, I 23 can't be sure, but that would sound approximately 24 correct. Page 396 1 Q. Well, is it your understanding 2 that the allegations were, at the time, that the 3 Prozac might be associated with this violent 4 aggressive act? 5 A. As I recall, those were the 6 allegations made by the Church of Scientology, 7 yes. 8 Q. When did the Church of 9 Scientology first come up in your investigation 10 of this incident, Doctor Heiligenstein? 11 A. It did not enter my 12 investigation as such. 13 Q. All right. So what the source 14 of this was didn't play any part in your 15 analysis, is that right? 16 A. No, it did not. 17 Q. Where did you hear that the 18 allegation was being made by the Church of 19 Scientology? 20 A. As I best recollect, by one of 21 their component organizations having been quoted 22 in the media. 23 Q. You read something in the 24 media? Page 397 1 A. As best I recollect, yes. 2 Q. Did you read that 3 independently or did you have somebody give you 4 material from the media to read? 5 A. I don't recall specifically if 6 the source was from local newspapers versus a 7 national newspaper versus something from 8 Louisville. 9 Q. Was there a Church of 10 Scientology listed on the 1639 that was filed in 11 connection with this incident? 12 A. Not that I recall. 13 Q. Do you recall the 1639 that 14 was filed in connection with this incident? 15 A. I recall there was a 1639, I 16 do not recall the specifics of the actual filing. 17 Q. Do you recall that the 18 coroner, who was by statute in Kentucky charged 19 with the responsibility of investigating this 20 incident, had raised a question with respect to 21 whether or not Fluoxetine was involved in this 22 man's conduct? 23 MR. MYERS: Object to the form. If 24 you know, tell him. Page 398 1 A. Would you repeat that 2 question, please? 3 MR. SMITH: Read it back, please. 4 (THE COURT REPORTER READ BACK THE 5 REQUESTED TESTIMONY.) 6 A. I recollect that that may have 7 been the case. 8 Q. All right. So I would assume 9 that you and others in the medical component at 10 Eli Lilly and Company were taking seriously from 11 whatever source you heard the allegation that 12 this incident might have been related to 13 Fluoxetine, Prozac, in some manner, isn't that 14 correct? 15 A. As best I recollect, we did 16 take very seriously that events had occurred, and 17 in terms of this relationship to when the 18 individual had been treated with Prozac was, as I 19 recall, a bit uncertain at that time. 20 Q. All right. Regardless, in 21 connection with respect to the time Mister 22 Wesbecker had last ingested Prozac, there was a 23 serious issue being raised by the coroner and by 24 the investigatory bodies in Kentucky in Page 399 1 connection with whether or not Prozac was in any 2 way related to this incident, correct? 3 MR. MYERS: I object to the form and 4 the use of the term investigatory bodies as being 5 undefined, I don't know what you're talking 6 about. If you know, tell him. 7 MR. SMITH: Grand juries. 8 MR. MYERS: Okay. 9 A. Repeat the question, please. 10 (THE COURT REPORTER READ BACK THE 11 REQUESTED TESTIMONY.) 12 A. I have some recollection that 13 that indeed did occur. 14 Q. All right. So you set out to 15 make an analysis of whether or not Prozac was 16 associated with a violent aggressive act in 17 general? 18 A. That's correct. 19 Q. Did you do any investigation 20 yourself to determine whether or not Prozac was 21 involved in the violent aggressive acts involving 22 Mister Wesbecker at the Standard Gravure plant in 23 September of 1989? 24 A. Can you help me with what you Page 400 1 mean by investigation myself? 2 Q. Well, did you, as a clinical 3 research physician, make any investigation 4 yourself in response to a 1639 or any other 5 method to determine whether or not there was a 6 causal relation between Mister Wesbecker's 7 conduct and his taking of Prozac? 8 A. I do not recollect that I 9 initiated any specific investigation relative to 10 that event. 11 Q. Do you know of anybody at Eli 12 Lilly and Company that did? 13 A. As I recall, we tried to 14 gather as much information as we could to augment 15 whatever initial information had been received. 16 If that's broadly defined in investigation, then 17 that of course would have been undertaken to 18 provide, again, as much information to -- for 19 reporting, to report. Additional investigations, 20 I cannot recall specific efforts. 21 Q. Do you know of anybody at Eli 22 Lilly and Company that made an investigation to 23 determine whether or not the acts of Joseph 24 Wesbecker at the Standard Gravure plant in Page 401 1 September, 1989 were related in any way to his 2 ingestion of Prozac, Fluoxetine Hydrochloride? 3 A. I don't recall. 4 Q. Do you think this would be 5 something that you would recall if such an 6 investigation was made? 7 A. Apart from gathering 8 additional information, I guess I'm not sure 9 apart from that what kind of investigation would 10 be -- you would be speaking of. 11 Q. Well, as a clinical research 12 physician at Lilly, you for some time before and 13 to a great deal afterward reviewed 1639s to 14 determine whether or not there was a causal 15 relation between the adverse event reported and 16 the use of Prozac, did you not? 17 A. That's correct. 18 Q. Did you ever do that in 19 connection with the Joseph Wesbecker incident in 20 September, 1989 where he killed seven or eight 21 people and injured approximately twenty people at 22 the Standard Gravure plant? 23 A. I do not recall that I 24 specifically did that. Page 402 1 Q. Do you know if anybody did at 2 Eli Lilly and Company? 3 A. There may have been someone 4 who would have perhaps contacted the prescribing 5 physician to get more information, would have 6 perhaps contacted the coroner's office to get 7 more information, as I may recall, relative to 8 any further information that they may have. 9 Q. Who would have done that? 10 A. I have a vague recollection 11 that there was a phone call with the coroner to 12 secure more information, and I don't know who 13 would have contacted the prescribing physician 14 directly. I do not recall that it was I, 15 although it's not entirely out of the range of 16 possibilities. 17 Q. Do you know if the telephone 18 conversation with the coroner in Louisville, 19 Kentucky confirmed that indeed Joseph Wesbecker 20 had therapeutic levels of Fluoxetine 21 Hydrochloride, that is Prozac, in his blood? 22 A. There are no therapeutic 23 levels for Prozac. 24 Q. There are no therapeutic Page 403 1 levels for Prozac? 2 A. No. 3 Q. Then how does anybody know how 4 much Prozac to give to anybody? 5 A. It's based -- in terms of 6 prescribing a medication like Prozac, it's 7 oftentimes based upon one's assessment of 8 clinical response. 9 Q. So it's kind of a hit or miss 10 proposition as to whether or not a particular 11 dosage should be prescribed to a particular 12 individual? 13 MR. MYERS: I object to the form, 14 that's not what he said, that's what you said. 15 A. There has been a dose 16 established which is an efficacious dose. 17 Q. So what is that? 18 A. Twenty milligrams. 19 Q. All right. Does that convert 20 to levels in blood? 21 A. Not in an absolute way that 22 would prevent response. 23 Q. All right. How does a 24 physician know how much Prozac to give to a Page 404 1 patient or whether or not a patient has indeed 2 been consuming Prozac by a blood test? 3 A. A physician does not have need 4 of a blood test for levels of Prozac to determine 5 whether the compound is efficacious. 6 Q. So if you feel better, then 7 you're prescribing an appropriate level of 8 Prozac, is that right? 9 MR. MYERS: I object to the form, 10 that's not what he said. Go ahead and answer, 11 Doctor. 12 A. Would you repeat the question, 13 please? 14 (THE COURT REPORTER READ BACK THE 15 REQUESTED TESTIMONY.) 16 A. I don't think that's entirely 17 correct. I think the way I would look at that is 18 that there is a recommended dose of Fluoxetine. 19 That would be the recommended dose that an 20 individual should begin with, and then one gauges 21 the response of the patient and makes decisions 22 about the benefit to some extent over the course 23 of time. 24 Q. What is the recommended dose? Page 405 1 A. The recommended dose? 2 Q. Uh-huh. 3 A. The recommended starting dose 4 is twenty milligrams. 5 Q. If a person takes twenty 6 milligrams of Prozac, can that be reflected in 7 the blood test taken sometime thereafter? 8 A. There would be in -- across 9 individuals, there would be a variability in the 10 levels that would be measured, even after a 11 single dose. 12 Q. All right. So you don't know 13 how much Prozac is going to be in your blood 14 after you take a single twenty milligram dose, it 15 depends on a variety of individuals? 16 A. It depends -- it would be a 17 range. If you sampled X number of people, there 18 would be a range which most people would fall 19 within. 20 Q. Okay. What is that range? 21 A. I don't recall. 22 Q. Why? 23 MR. MYERS: Why doesn't he recall? 24 MR. SMITH: Yes. Page 406 1 A. Because that range does not 2 necessarily or specifically relate to efficacy. 3 Q. Okay. Well, then, how do you 4 know whether you have taken enough Prozac if that 5 range doesn't determine efficacy? 6 A. You assess -- I would assess 7 the clinical state of the patient. 8 Q. Okay. So you don't know 9 whether the dose is appropriate from a 10 therapeutic standpoint until after you begin the 11 dose and have the opportunity to assess the 12 patient, is that what you're telling me? 13 A. No, that's not what I'm 14 telling you. What I'm telling you is that there 15 is a dose which captures, relative to efficacy, 16 what I might say would be the greatest number of 17 people who would be likely to respond. That dose 18 is what, as a clinician, I would initially 19 prescribe. 20 Q. But you can't predict -- is 21 what you're telling me, you can't predict how 22 much Prozac you're going to find in the blood 23 after somebody takes that dose? 24 A. You would have a range that Page 407 1 has been reported. That range may be rather 2 wide, it may have a few, you know, people who 3 would be outside the range, but there would be, 4 in general, a range. 5 Q. And you don't know what that 6 range is? 7 A. I would have a guesstimate for 8 the parent compound. I would -- as I vaguely 9 recall, somewhere in the range of a hundred to 10 three hundred nanograms, as I seem to have some 11 recollection. 12 Q. That's quite a range, isn't 13 it, Doctor, one hundred to three hundred? It's 14 three times variability there, don't you? 15 A. Well, from the bottom to the 16 top, one could say there's a three-fold 17 difference, yes. 18 Q. You don't prescribe Prozac, do 19 you? 20 A. No, I don't. 21 Q. Because you're not in clinical 22 practice. 23 A. That's correct. 24 Q. But you are charged and have Page 408 1 been charged in the past with evaluating adverse 2 experiences by people taking Prozac, correct? 3 A. I have been charged with 4 evaluating events as they're reported relative to 5 relationship, in a situation where the event is 6 serious. 7 Q. And suspected to be adverse to 8 the patient? 9 A. Yes. That doesn't always 10 imply causality. 11 Q. I understand that. But you're 12 the physician charged with making some 13 investigational causability at Eli Lilly and 14 Company, aren't you? 15 A. That's correct. 16 Q. But you don't know, as we sit 17 here today, what a therapeutic blood level is 18 with respect to an individual taking Prozac? 19 A. That has been studied 20 extensively, and there is no correlation between 21 blood levels and efficacy. 22 Q. So it's not some information 23 that you use from a day-to-day basis? 24 A. Pardon? Page 409 1 Q. So that's not information that 2 you use from a day-to-day basis? 3 A. I'm aware that there is no 4 relationship, and so if that question is posed 5 with me, I can answer the question. 6 Q. How can we determine, from a 7 scientific standpoint, whether Prozac is related 8 to a particular adverse event? 9 A. It's very difficult. 10 Q. Why? 11 A. Because there are many events 12 that occur in an individual's life that may 13 affect their general physiological functioning 14 that may bear no relationship -- in some cases 15 they may not be taking any medication, in other 16 instances they may be taking a medication for 17 which one cannot necessarily make the association 18 that because the event occurred it's related to 19 substance X, Y or Z. 20 Q. But you know that there are 21 certain adverse events that you found in 22 connection with Prozac that are caused by, in 23 your opinion, the ingestion of Prozac by the 24 patient, aren't there? Page 410 1 A. There are adverse events which 2 occured frequently during clinical trials that 3 occurred with, one might say, significantly 4 greater frequency in the Fluoxetine group as 5 compared to a placebo group. 6 Q. So you've determined, based on 7 that experience, that that is -- that particular 8 adverse event was causally related to the Prozac? 9 A. Not in every instance, because 10 the same events could have occurred on placebo at 11 a high percentage as well, it's just that maybe 12 twenty-five percent versus fifteen percent. That 13 does not mean that every such event, such as 14 nausea, which may occur with Fluoxetine, is 15 nausea caused by Fluoxetine. 16 Q. Certainly, absolutely, but 17 there are certain events that you have found that 18 are causally related in a particular instance to 19 the ingestion of Prozac, aren't there? 20 A. If I understand your question, 21 then I would say that those events are not 22 necessarily causally related to Fluoxetine in 23 every instance in which they're reported. 24 Q. I didn't say in every Page 411 1 instance. Listen to my questions, Doctor, and 2 we'll get through this a lot quicker. There are 3 events that are indeed causally related to 4 ingestion of Prozac, in your opinion, aren't 5 there? 6 A. There would be, yes. 7 Q. Give me an example of an 8 adverse event that you have determined is in a 9 particular instance causally related to the 10 patient's taking of Prozac. 11 A. With the frequently occurring 12 adverse events, I'm oftentimes not asked to make 13 any kind of causal relationship. 14 Q. I'm asking you to give me an 15 example of an instance in which you've 16 determined, as a clinical research physician, 17 senior now, clinical research physician, at Eli 18 Lilly and Company, that a particular adverse 19 event was related to the patient's ingestion of 20 Prozac. 21 A. I think some instances of 22 severe nausea. 23 Q. All right. Let me write that 24 down. What did you do in this particular Page 412 1 instance to determine that the severe nausea, in 2 that instance, was causally related to the 3 patient's ingestion of Prozac? 4 A. Well, I had to use my -- I 5 didn't necessarily do anything specific. What I 6 would have done is when I reviewed that event, 7 and let's say -- well, I wouldn't even have had 8 to have made that call, quite frankly. But if I 9 had signed off on the 1639, in which a patient 10 had severe nausea and was hospitalized, then 11 because it would be expected, I still wouldn't 12 have to make a causal association. 13 Q. I understand that, I 14 understand that severe nausea can be caused by a 15 myriad of physical complaints, can't it, you can 16 tell us that as a physician, can't you? 17 A. That's correct. 18 Q. But that's not the issue 19 before you as a clinical research physician in 20 trying to make a determination with respect to 21 whether or not Prozac caused that nausea in that 22 particular individual, is it? 23 A. I'm sorry, repeat that. 24 Q. That's not the issue that you Page 413 1 have to look at in connection with whether or not 2 Prozac caused a particular individual's nausea, 3 that is the fact that many things can cause 4 nausea? 5 A. That is something I would 6 consider if the event would be a serious event 7 and if causality was expected to be assigned. 8 Q. I want to know from -- and I 9 understand you understand and consider that 10 nausea may be caused by many things. I want to 11 know what you do to make an analysis that this 12 particular instance of nausea was caused in this 13 particular instance by this particular patient's 14 ingestion of Prozac? 15 A. Well, given that -- again, 16 that's if I were to do that, because I'm not sure 17 I would ever have to do that with nausea, given 18 that it's an expected event -- 19 Q. I'm just using your example. 20 A. It's a poor choice of an 21 example. 22 Q. Give me a better example then. 23 A. I would -- probably a better 24 example would be the -- where I would need to Page 414 1 assign causality would be the interaction of 2 Fluoxetine with amino oxydase inhibitor. 3 Q. I'm talking about an adverse 4 event. 5 A. Where an individual 6 experienced -- I'm thinking about -- the package 7 insert is so inclusive, I'm trying to think of an 8 example where I would be called upon to make that 9 causality assessment. 10 Q. Don't you -- 11 MR. MYERS: Let him finish. Go ahead 12 and finish, Doctor. 13 A. I was saying that where one 14 needs to make a causality statement for 15 regulatory purposes, that's what I'm referring to 16 because the package insert is so inclusive. 17 Q. Don't confine yourself, 18 Doctor, to regulatory purposes. Why don't you 19 speak from a scientific standpoint as a medical 20 doctor trained in psychiatry, neurology, and 21 principles of anatomy and medicine? I'm not 22 asking you to be a regulatory employee, I'm 23 asking you to be a doctor. 24 A. Well, that's in the context of Page 415 1 which I make those decisions. So let me present 2 an example to you then where an event would have 3 been characterized as unexpected, and where I 4 would need to make some assessment. In patients 5 who died as a result of taking Fluoxetine in 6 close proximity to monoamine oxydase inhibitor. 7 Q. So you've got a death? 8 A. That's correct. 9 Q. So the event that you're 10 trying to determine whether or not is related to 11 Prozac is an individual's death, okay? 12 A. That's correct. 13 Q. What do you do, and I'm 14 talking -- I want you to give me an example where 15 you conclude that Prozac was causally related to 16 the individual's -- to the adverse event 17 reported. 18 A. Of course that assignment of 19 causality, is it reasonable, is it possible, so 20 it doesn't necessarily mean that one is a hundred 21 percent certain that that event was causally 22 related. 23 Q. I understand that. From a 24 medical standpoint, your best clinical judgement Page 416 1 with respect to whether or not it's related. 2 A. I find that there is a very 3 close proximity with my clinical judgment and the 4 regulatory reporting requirement. 5 Q. All right. 6 A. Would you like for me to 7 return to that earlier example of a monoamine 8 oxydase inhibitor? 9 Q. Yes. You've got a death in 10 connection with a patient who has been taking 11 Prozac, and you're trying to determine as a 12 clinical research physician at Lilly whether or 13 not that death was related to that patient's 14 taking Prozac. 15 A. In that particular instance it 16 would be the results of an interaction with 17 Fluoxetine and a monoamine oxydase inhibitor. So 18 what I would do, in response to your question, as 19 best I understand it, is that I would initiate a 20 call to the reporter of the event. 21 Q. All right. 22 A. And I would seek to obtain 23 information relative to the medications as they 24 were prescribed, and other concomitant Page 417 1 medications, and any other information that would 2 be available from the patient's -- from the 3 physician's recollection, and obtain information 4 from the coroner, if that was accessible. 5 Q. Or medical -- when you say 6 coroner -- when you say medical examiner or 7 somebody that might have done a post mortem or 8 autopsy on the patient? 9 A. That's correct. 10 Q. I have written down you call 11 to the reporter of the event to get the 12 medications that were prescribed, and I would 13 imagine that would include the dosage of Prozac? 14 A. Yes, sir. 15 Q. And the time that it was last 16 reported that the patient had taken the Prozac? 17 A. The duration of treatment, 18 right. 19 Q. And then you would want to 20 know what concomitant medications were involved? 21 A. I would want as much 22 information as I could have, and that would 23 include concomitant medications, concurrent 24 illnesses. Page 418 1 Q. Let me write that down, 2 concurrent illnesses. What else? 3 A. I would want to know what 4 information, if any, was available from the post. 5 Q. Such as? And again, confine 6 yourself to this inquiry with respect to a death 7 being reported to you and you learned at the time 8 it was reported to you that the patient was also 9 taking a monoamine oxydase inhibitor? 10 A. I would want to know if the 11 medical examiner indeed screened for other 12 substances. 13 Q. Well, that would be something 14 that would be determined in the autopsy, would it 15 not? 16 A. Yes, sir. And in addition, 17 whether levels of any of those substances which 18 were reported were available. 19 Q. Why would that be important 20 with Prozac since you don't know in connection 21 with Prozac what a therapeutic dosage of Prozac 22 is or that bears no relationship to blood levels? 23 A. It wouldn't help relative to 24 Prozac other than to say that the Prozac was on Page 419 1 board, meaning the patient had taken Prozac and 2 there were still detectable levels. 3 Q. Go ahead, what other 4 information and investigation would you make into 5 this incident? 6 A. I'm sure that there's 7 additional information that I would request from 8 the research -- or the prescriber, I'm sorry, but 9 that escapes me right now. What I would like to 10 do is get as much information as possible. Then, 11 because I'm aware that there is a potential for 12 interaction of these compounds, and we have 13 investigated that in the past, and that's 14 reflected in the package labeling, then I would 15 be responsible for assigning causality. 16 Q. This is not a hypothetical 17 question as far as you're concerned, you have 18 actually done this on many occasions, that is 19 make the determination with respect to whether or 20 not there is a causal relationship between Prozac 21 and a particular adverse event, haven't you? 22 A. That's correct. 23 Q. How many times would you say 24 over your career with Lilly have you done that? Page 420 1 A. It's hard to estimate. 2 Q. Give me your best estimate. I 3 didn't promise my questions would be easy or 4 understandable. 5 MR. MYERS: Stipulated. 6 A. Where I would be assigning 7 expectancy -- or causality, I'm sorry -- well, I 8 would do both, one leads -- it's an algorithem. 9 Where I would be expected to assign causality, I 10 would say probably several hundred times, at 11 least. 12 Q. Well, that would be anywhere 13 from two hundred to nine hundred and ninety-nine 14 times. Can you give me a better estimate? 15 A. I would guesstimate somewhere 16 between a hundred and fifty and maybe four 17 hundred and fifty. 18 Q. All right. In this instance 19 that we talked about, you talked to the reporter 20 of the event, correct? 21 A. That's correct. 22 Q. And based on that 23 conversation, and based on information that you 24 learn, you make a determination that the event, Page 421 1 that is the death, was caused by Prozac, correct? 2 A. That there may be a causal 3 relationship or possible causal relationship. 4 Q. All right. What factors in 5 this situation would point to the fact that there 6 is a causal relationship of Prozac in this 7 adverse event? 8 A. What it would be that would be 9 possibly causally related would be some sort of 10 interaction between Fluoxetine and a monoamine 11 oxydase inhibitor that would lead to the cascade 12 of events that then would have led to a patient's 13 death. There is, as I recall, some literature in 14 some animal studies that suggests there may be 15 some interaction of selective serotonin uptake 16 inhibitors with a compound like transylpromine. 17 Q. Okay. So you evaluated, and I 18 want to know what factors you considered. You 19 considered the dosage of Prozac and the duration 20 of Prozac? 21 A. That's information I would 22 find helpful, it would not be the ultimate 23 consideration. The ultimate consideration that 24 would help me would be was there indeed Page 422 1 detectable levels of the compounds that may have 2 contributed to an individual's demise that one 3 could then make that judgment. 4 Q. Whether or not there was 5 actually Prozac on board would be the critical 6 item in this particular determination for you, is 7 that right -- 8 A. That would be -- 9 Q. -- as opposed to whether or 10 not the medication had been prescribed at a 11 certain dosage for a certain length of time? 12 MR. MYERS: Go ahead. 13 A. That's correct. 14 Q. But there are other instances 15 when you want to know what the dosage is and what 16 the duration of the dosage of Prozac is in order 17 to assist you in determining whether or not 18 Prozac was causally related to the adverse event? 19 MR. MYERS: Outside of this example 20 you've been talking about? 21 MR. SMITH: Yes. 22 A. That's possible. 23 Q. For instance, if you were 24 looking at a rash, in determining whether or not Page 423 1 the Prozac caused the rash, you could very likely 2 not have any blood work that would indicate 3 whether or not Prozac was actually on board, 4 correct? 5 A. That's correct. 6 Q. But you could make some 7 statements concerning causality in that 8 particular rash if you knew the dosage of Prozac 9 and the duration of that dosage with respect to 10 the Prozac? 11 A. Rash is a very big example 12 because it's so hard to make an assessment of 13 causality of the occurrence of rash with a given 14 compound, especially as rash -- given that rashes 15 can occur de novo, when an individual is not 16 taking any medication, one would need more 17 specific information. 18 Q. I understand that. The only 19 point I'm making, and I'm not trying to trap you 20 into some particular position, Doctor, is 21 sometimes -- I'm trying to get the factors that 22 you examine in determining whether or not there 23 is a causal relationship between the reported 24 adverse event and the ingestion of Prozac, and I Page 424 1 think one of the items that you gave in your 2 example was whether or not Prozac was on board by 3 virtue of blood studies done on the patient, 4 correct? 5 A. That's correct. 6 Q. But you might not always have 7 that information, and you might be able to 8 determine -- you've got to at least know that the 9 patient was indeed taking the Prozac, so you 10 might be able to get that information simply by 11 virtue of the fact that there was a prescription 12 of Prozac written over a particular period of 13 time at a particular dosage, correct? 14 A. That's correct. 15 Q. All right. Now what other 16 factors are significant to you in making this 17 investigation other than the dosage and duration 18 of Prozac or whether or not there is Prozac found 19 in the blood studies of the particular patient in 20 question? 21 MR. MYERS: Are you back to the 22 example now? 23 MR. SMITH: Yes. 24 A. I'm sorry, which example are Page 425 1 you referring to now, the monoamine oxydase 2 inhibitors? 3 MR. SMITH: Yes. 4 A. I would have information, of 5 course, information and data available from prior 6 such occurrences that may help shed some light, 7 as well as I mentioned perhaps some studies in 8 animals. I know that we undertook a study in 9 animals upon reports of the potential for an 10 interaction problem. 11 Q. Could it be accurate to 12 describe that is that that particular adverse 13 event has been experienced in the past in 14 connection with Prozac? 15 A. If I was reviewing an event 16 today, yes, that would be the case. I would have 17 some model, some information relative to a 18 composite of information that had been gathered 19 over a course of time. 20 Q. For instance, we know -- 21 there's been no -- I assume there's been no 22 reported instances of Prozac causing pregnancy in 23 women? 24 A. People have claimed a lot of Page 426 1 things, but that's not -- 2 Q. There have not been reports of 3 that in the literature of any scientific basis to 4 establish Prozac and pregnancy in women, has 5 there? 6 A. No, not in the scientific 7 literature as far as I'm aware of. 8 Q. I may have used a ridiculous 9 example, but certainly in making a determination 10 concerning whether or not Prozac caused a 11 particular adverse event, you want to know what 12 the past scientific experience has been in 13 connection with other examinations of this issue, 14 don't you? 15 A. I think you're suggesting that 16 as much information that's available as possible, 17 one should try and bring into bear on that 18 process, and I would agree. 19 Q. I'm trying -- we're going to 20 get other information, but right now I'm talking 21 about scientific experience -- 22 A. That's correct. 23 Q. -- as an element. So what 24 I've got here is I've got dosage and duration of Page 427 1 Prozac or -- and/or Prozac in the bloodstream or 2 in blood studies, and data from prior occurrences 3 mentioned in scientific literature? 4 A. Or available to us through our 5 data base. 6 Q. All right. So would that be 7 another factor that you consider, whether or not 8 it had been reported to you in the past? 9 A. For a serious unexpected 10 event, we might very well search the data base. 11 Q. What other information are you 12 going to need to determine whether or not the 13 particular adverse event was causally related to 14 the ingestion of Prozac? 15 A. I believe we have covered the 16 scientific literature. Off the top of my head, I 17 can't think of other sources, but there may very 18 well be. 19 Q. So this information that 20 you've given me, the dosage and duration of 21 Prozac or the presence of Prozac in blood 22 studies, whether or not this particular event had 23 been reported in the past and had been the 24 subject of scientific investigation, those are Page 428 1 all the data or factors that you need in 2 determining whether or not this particular 3 adverse event was causally related to the 4 ingestion of Prozac? 5 A. I would also need some more 6 specific information from the medical examiner 7 about any other substances which were identified 8 in the post. So, for example, we know that 9 alcohol interacts with monoamine oxydase 10 inhibitors, we know that tyelomine containing 11 compounds do as well so that would be important 12 information to have that for the most part won't 13 obtained from the benefit of the post or perhaps 14 some historical data provided to a physician by a 15 family member or a friend of the deceased. This 16 in this particular instance, that would be a 17 substance amount of the information that I need. 18 Q. All right. Can you think of 19 other instances in making the determination with 20 respect to other adverse events where you would 21 need additional information, Doctor? 22 A. In other adverse events? 23 Q. Yes. 24 A. Yes. Page 429 1 Q. By the way, let me digress. 2 Is there a checklist or is there a form or 3 anything written that you use or fill out when 4 you're making these investigations concerning 5 whether or not a particular adverse event is 6 causally related to the use of Prozac? 7 A. If you're asking if there's 8 some specific operational form, no, there's not, 9 to my knowledge. Not one that I use. 10 Q. I don't want to mislead you, 11 but it's my understanding from prior depositions 12 there may be forms that are filled out by support 13 staff or other individuals at Lilly getting vital 14 statistics and things of that nature. 15 A. Oh, that's correct. When an 16 event is called in, if it comes to me as a 17 physician, then I have a 1639 that I do in 18 longhand. 19 Q. I understand that. But there 20 are additional forms, are there not, providing 21 information for you filled out by those people 22 talking with the reporters? 23 A. There are some additional 24 forms. Page 430 1 Q. What are those forms called? 2 A. I guess I could best 3 characterize those as informational-gathering 4 forms. They could be a form very similar to what 5 I fill out if I take a call from a physician, 6 such as more or less a blank 1639, and they can 7 report that information there. There can also be 8 information that is provided from the sales force 9 staff about a physician reporting an event that 10 is taken and incorporated into a form that is 11 used for that purpose and then becomes 12 transcribed or gets transcribed on a 1639 in a 13 formal fashion. 14 Q. What is the name of that form? 15 A. I don't know what the name of 16 that form is. 17 MS. ZETTLER: Working 1639? 18 THE WITNESS: I don't believe that's 19 how it's titled. 20 Q. Or working forms or working 21 papers? 22 A. I want to say that it's some 23 sort of phone message form, some telephone 24 communication form. Page 431 1 Q. All right, okay. I digressed. 2 You were going to tell me other information that 3 you would need in other instances with respect to 4 other adverse events. 5 A. I would want to know about the 6 patient's -- about the patient's illnesses. 7 Q. That might be relevant in some 8 inquiries, but it might not be relevant in others 9 in determining causality? 10 A. That's correct. 11 Q. All right. What else? 12 A. For a serious unexpected 13 report, I might -- if there are physician records 14 available, I might request that or a consultant's 15 report, for instance. It would depend upon the 16 report, of course. What other source of 17 information -- I'm sorry. What other information 18 would I need, is that the question? 19 Q. What other factors would you 20 evaluate or what other information would you need 21 in determining whether or not Prozac was causally 22 related to the adverse event being reported? 23 A. What would be helpful 24 information is the physician's sense of Page 432 1 relatedness or not relatedness. 2 Q. The treating physician's 3 opinion? 4 A. Yes, sir. I can't think of 5 other information that I would -- at this time I 6 can't think of other information that I would be 7 requesting. 8 Q. Now, back to Joseph Wesbecker. 9 Did you ever call the individual who made or 10 reported this tragedy in Louisville to Lilly? 11 MR. MYERS: He personally? 12 Q. I said you. 13 MR. MYERS: Nancy used the word you to 14 mean some other things earlier. 15 A. I do not recall that I placed 16 such a call. That does not mean that one did not 17 occur, I just don't recall doing that. 18 Q. Do you know if anybody at Eli 19 Lilly did? 20 A. Well, as I best recall, the 21 media was the reporter, the avenue for that 22 information coming to Lilly as best I recollect. 23 And -- 24 Q. Did you call -- Page 433 1 MR. MYERS: Let him finish. Go ahead 2 and finish your answer, Doctor. Please don't 3 interrupt him, Paul. Go ahead and finish. 4 A. As I recall, that information 5 came via the media, and there may have been some 6 calls initiated after that, but I do not recall 7 myself initiating that, it may have been a 8 colleague or somebody else. 9 Q. Do you know if anybody at 10 Lilly called the newspaper or the initial 11 reporter of this particular tragedy? 12 A. I did not. I don't know if 13 anyone did. 14 Q. Did you gain any information 15 with respect to the dosage or duration of dosage 16 that Mister Wesbecker was taking? 17 A. Could you repeat that, please? 18 (THE COURT REPORTER READ BACK THE 19 REQUESTED TESTIMONY.) 20 A. I did not specifically through 21 a direct contact, as best I recollect, but I do 22 recall that that information was obtained. 23 Q. And what information was 24 learned in connection with the dosage that Joseph Page 434 1 Wesbecker was taking and the duration for which 2 he had been taking Prozac? 3 A. I don't recall specifics. 4 Q. Who would know that? 5 A. I would suspect that that 6 information would be available in the 1639, and 7 other individuals who may have a better 8 recollection might recall those specifics. 9 Q. Who might have a better 10 recollection of this at Lilly? 11 A. Doctor Beasley. 12 Q. Charles Beasley? 13 A. Yes, sir. Possibly Doctor 14 Thompson. 15 Q. Which Doctor Thompson? 16 A. Doctor Leigh Thompson. 17 Possibly -- I don't know anyone -- I don't know 18 others who might recall it more specifically than 19 that, than those two I just mentioned. 20 Q. As far as you know, the only 21 people working on the Wesbecker situation was 22 you, Doctor Charles Beasley, and Doctor Leigh 23 Thompson? 24 A. No. Page 435 1 Q. All right. 2 A. Doctor Masica would have been 3 involved, Doctor Zerbe would have been involved. 4 Q. Anybody else, is that all? 5 A. Possibly Doctor Wheadon. And 6 I'm not sure that Doctor Street was involved in 7 any of this or not. 8 Q. Anybody else? 9 A. Doctor Kotsanos may have been 10 involved at some point. Possibly, I think it 11 unlikely, but possibly Doctor Talbott. I think I 12 have been about as inclusive as I can be. There 13 may -- 14 Q. As I understand your 15 testimony, these are the individuals that might 16 have been involved in the Joseph Wesbecker 17 situation, but you're not certainly telling us 18 that all of these people were involved? 19 A. That's correct. 20 Q. You were involved? 21 A. Yes, sir. 22 Q. Were you heading up or in 23 charge of this investigation? 24 A. No, sir. Page 436 1 Q. Who was? 2 A. I don't recall specifically. 3 I can suggest several people, one of whom may 4 have been the overall point person for this. 5 Q. Okay. 6 A. This specific incident. 7 Q. Yes. 8 A. Doctor Zerbe, Doctor Masica. 9 To my way of thinking, those would be the two 10 most likely. 11 Q. Do you recall getting the 12 instructions from either Doctor Zerbe or Doctor 13 Masica in connection with your investigation and 14 your work on the Wesbecker situation? 15 A. As I recall, I was requested 16 to sit in on a phone conversation that some 17 individuals had with the medical examiner. 18 Q. All right. Who all was 19 involved in this phone conversation? 20 A. As best I recollect, Doctor 21 Thompson. 22 Q. Leigh Thompson? 23 A. Yes, sir. Doctor Masica, and 24 Doctor Zerbe. Page 437 1 Q. And the medical examiner was 2 on the phone, too? 3 A. As I recollect, yes. 4 Q. The medical examiner in 5 Louisville, Kentucky? 6 A. Yes, sir. 7 Q. Now is it your understanding 8 that that medical examiner in Louisville, 9 Kentucky, is the same individual that is the 10 coroner in Louisville, Kentucky? 11 A. That would be my supposition, 12 but I have nothing to base that on. 13 Q. Is it your recollection is 14 that that discussion with the medical examiner 15 concerned results of an autopsy or postmortem 16 done on Mister Wesbecker? 17 A. As best I recall. 18 Q. Is that a yes? 19 A. Yes, sir. 20 Q. When did this conversation 21 occur? 22 A. I don't recall the specific 23 date. I would suggest that it would have been 24 sometime between the actual occurrence of the Page 438 1 event and the end of that year, which would have 2 been '89, am I right, '89? So I think it would 3 probably have been sometime between that event 4 and the end of the calendar year. 5 Q. All right. The event occurred 6 on September 14, 1989. 7 A. Uh-huh. 8 Q. Is that a yes? 9 A. I'm trusting that that's 10 correct, I don't know for a fact. 11 Q. When in connection with 12 September 14, 1989 was this phone conversation 13 between you, Leigh Thompson, Dan Masica and 14 Doctor Zerbe and the medical examiner? 15 A. I don't recall. 16 Q. Was it within a week? 17 A. Not that I recall. 18 Q. Was it within the month of 19 September? 20 A. I don't recall. 21 Q. Would it have been in October? 22 A. Possibly. 23 Q. Probably? 24 A. I'm sorry, I just don't Page 439 1 recall. 2 Q. Do you remember having -- that 3 this conversation that you had with the medical 4 examiner was one of the first things that was 5 done in connection with the investigation of this 6 incident? 7 A. I don't recall that it was one 8 of the first things that was done. I think it 9 was one of the things that was done as part of a 10 number of things that were done. 11 Q. Was this phone conversation 12 before or after the coroner's inquest? 13 A. I don't recall. 14 Q. As part of your investigation, 15 did you attend the coroner's inquest? 16 A. I did not. 17 Q. Did somebody from Lilly attend 18 the coroner's inquest? 19 A. I have a vague recollection 20 that someone did. 21 Q. Who would it have been? 22 A. I don't know. 23 Q. Have you ever read a 24 transcript of the coroner's inquest? Page 440 1 A. Not that I recall. 2 Q. Would that contain data that 3 would be relevant to you in making a 4 determination with respect to whether or not 5 Prozac was involved in this tragedy? 6 A. That would be information that 7 one would incorporate into a larger body of 8 information, yes. 9 Q. So it would be relevant? 10 A. It would be relevant. 11 Q. What else -- oh, I was trying 12 to help and grasp with you when this phone 13 conversation with the medical examiner would have 14 been, and you think it was at least before the 15 end of 1989? 16 A. To the best of my 17 recollection. 18 Q. Would you have made notes in 19 connection with that phone conversation with the 20 medical examiner? 21 A. I don't believe that I did. 22 Q. Wouldn't somebody have made 23 notes in connection with the conversation with 24 the medical examiner? Page 441 1 A. It's possible. 2 Q. That makes sense, doesn't it, 3 that you're making an investigation and you're 4 trying to get information from the medical 5 examiner concerning a massive tragedy, wouldn't 6 somebody be taking notes to get for certain the 7 data that was being transcribed or transmitted to 8 them by the medical examiner? 9 A. As I understand, there would 10 be a formal transcript from that particular 11 office that then would be available. I don't 12 know that under the circumstances it would be 13 necessary to take notes in a conversation such as 14 that. 15 Q. What was the purpose of the 16 phone conversation? 17 A. As best I recall, to obtain 18 additional information. 19 Q. What information did you 20 obtain? 21 A. I don't recall. 22 Q. Do you recall obtaining any 23 information? 24 A. No, I don't. Page 442 1 Q. Do you recall whether or not 2 the autopsy or postmortem report was available -- 3 A. I do not recall. 4 Q. -- at the time of that 5 telephone conversation? 6 A. I don't recall. 7 Q. Do you recall any question 8 that anybody from Eli Lilly and Company asked the 9 medical examiner in that conversation? 10 A. No, I don't. 11 Q. Do you remember whether or not 12 the chief scientific officer of Eli Lilly and 13 Company, Doctor Leigh Thompson, ever made any 14 specific question to the medical examiner in 15 connection with his inquiry into this tragedy? 16 A. I'm sure there were questions, 17 I don't recall the specifics or the sense of 18 those questions. 19 Q. I'm asking whether or not 20 Doctor Leigh Thompson asked any specific 21 questions? 22 A. I don't know that. 23 Q. Do you remember Doctor Leigh 24 Thompson saying anything in this phone Page 443 1 conversation? 2 A. I don't recall. 3 Q. Do you recall Doctor Dan 4 Masica saying anything in this conversation? 5 A. I don't recall. 6 Q. What was Doctor Masica's 7 position at Eli Lilly and Company at the time of 8 this phone conversation? 9 A. He was a director of the, I 10 guess, the neuropsychopharm division at that 11 time. 12 Q. Do you remember anything 13 specifically that Doctor Robert Zerbe asked the 14 medical examiner? 15 A. I don't. 16 Q. What was Doctor Robert Zerbe's 17 position with Eli Lilly and Company at that time? 18 A. I believe Doctor Zerbe was an 19 executive director at that time. 20 Q. Executive director of what? 21 A. Of medical. 22 Q. Medical at Lilly Research 23 Labs? 24 A. As I recall. Page 444 1 Q. Was he corporate officer in 2 Lilly Research Labs at that time? 3 A. I don't think that position 4 would be considered a corporate officer. 5 Q. Doctor Leigh Thompson's 6 position was that of a corporate officer at that 7 time, wasn't it? 8 A. As I recall at that time he 9 was a vice-president of Lilly Research Labs, I 10 think that would qualify him, although I can't 11 say with any degree of certainty. 12 Q. Do you remember anything you 13 asked the medical examiner? 14 A. I don't recall saying a word. 15 Q. Do you recall anything that 16 the medical examiner said? 17 A. I have a vague recollection of 18 some comment of some frustration he may have 19 expressed with Scientologists being so involved 20 in all of this. 21 Q. Do you recall anything else 22 said in this conversation? 23 A. I sure can't. 24 Q. So it's your testimony here Page 445 1 today, in April, 1994, that in this phone 2 conversation between yourself and four scientists 3 at Eli Lilly and Company and the medical examiner 4 who was responsible for the autopsy or the 5 postmortem in connection with Joseph Wesbecker -- 6 in connection with Joseph Wesbecker's death, you 7 can remember nothing about that phone 8 conversation other than he was -- he, the medical 9 examiner, was frustrated about the Scientologists 10 being involved? 11 A. Yes, yes, sir. 12 Q. Have you ever had any 13 difficulty with your memory, Doctor 14 Heiligenstein? 15 MR. MYERS: Excuse me, Paul, don't 16 start to argue with him. That's an argumentative 17 question. He's answered your question about the 18 phone conversation, don't argue with him. 19 Q. Have you ever seen a physician 20 for problems with your memory? 21 MR. MYERS: Go ahead and answer that. 22 A. Have I seen a physician for 23 problems with my memory. Yes, as I recollect. 24 Q. When did you first see a Page 446 1 physician for problems with your memory? 2 A. Probably sometime in 19 -- I 3 didn't see it specifically for that. 4 Q. You made a complaint of memory 5 problems? 6 A. Yes, I saw someone, I don't 7 recall specifically, but maybe in 1984. 8 Q. What was the name of that 9 doctor? 10 A. Doctor Anton, A-N-T-O-N. 11 Q. A-N-T-O-N. Where was he 12 located? 13 A. At the Medical University of 14 South Carolina. 15 Q. Is he still there? 16 A. I don't know. 17 Q. Where was he when you last 18 knew where he was? 19 A. The Medical University. 20 Q. What's his position there? 21 A. He was either an associate or 22 full professor, I'm not sure. 23 Q. Of what? 24 A. Psychiatry. Page 447 1 Q. What was the memory problem 2 that you related to him? 3 A. I didn't relate a specific 4 memory problem. What I wondered about is whether 5 I didn't have an adult manifestation of attention 6 deficit hyperactivity disorder. 7 Q. Was one of the complaints that 8 you gave him was that you seem to have had 9 problems remembering things? 10 A. I remember -- I don't remember 11 specifically what I shared, but I suspect one of 12 my concerns was that storing of information was 13 not as good as what I thought it should be. 14 Q. And the retrieval of that 15 information was not as good as it should be? 16 A. I'm a pretty stern critic of 17 myself, yes. 18 Q. What other doctors -- what 19 other doctors have you seen for this condition 20 that you complained that caused memory problems? 21 A. None that I recollect. 22 Q. Did you advise anybody at Eli 23 Lilly and Company that you had reported memory 24 problems to a psychiatrist prior to your joining Page 448 1 their group? 2 A. I did not report, that I 3 recall, that I had seen a physician for the 4 possibility of an attention deficit disorder. 5 Q. Well, did you report to them 6 that you had reported to that physician that you 7 had memory problems? 8 A. Pardon? 9 Q. Did you report to Lilly that 10 you had seen a physician and made complaint of 11 memory problems? 12 A. I didn't make that specific 13 complaint. Those are your words, not mine. My 14 complaint was given that I had concerns as to 15 whether I might be an adult attention deficit 16 disorder to Doctor Anton, and his estimation -- 17 that he had enough information that that was a 18 possibility. I did not the report that to Lilly. 19 Q. Why? 20 A. Well, I didn't report, as I 21 recall, my full medical history. 22 Q. Did they ask you? 23 A. Not that I recall. 24 Q. Did they ask you if you ever Page 449 1 sought psychiatric treatment? 2 A. Not that I recall. 3 Q. Did you fill out an employment 4 questionnaire when you applied for employment 5 with Eli Lilly and Company? 6 A. Not that I recall. 7 Q. How many times did you see 8 Doctor Anton? 9 A. For this specific -- 10 Q. Yes. 11 A. -- problem? Because he was 12 also a friend and a colleague that I would 13 consult with relative to difficult clinical 14 situations. So relative to this -- 15 Q. I'm talking about your 16 clinical situation. 17 A. Maybe two or three times. 18 Q. Did he prescribe treatment? 19 A. As I recollect, he did. 20 Q. Did he prescribe 21 pharmacological treatment? 22 A. Yes. 23 Q. What medication did he 24 prescribe for this problem? Page 450 1 A. As I recollect, it was 2 Ritalin. 3 Q. Have you ever taken Prozac? 4 MR. MYERS: Don't answer that 5 question. You're going into something far 6 afield. Don't even respond to that, Doctor. I 7 direct you not to answer that. 8 MS. ZETTLER: Certify it. 9 (QUESTION CERTIFIED.). 10 Q. Have you ever taken Prozac for 11 attention deficit disorder or memory problems? 12 MR. MYERS: You can answer that. 13 A. No, I have not. 14 Q. Have you yourself ever 15 suffered depression? 16 MR. MYERS: Don't answer that. Paul, 17 you're going far afield. I gave you a lot of 18 latitude on that one line of questioning, and 19 you're not going any further, so move on to 20 something else. 21 MS. ZETTLER: Certify it. 22 (QUESTION CERTIFIED.). 23 Q. Have you seen any other 24 physicians for either attention deficit disorder Page 451 1 or made complaints of memory problems to any 2 other physicians? 3 MR. MYERS: Go on and answer that. 4 A. No, I have not. 5 Q. Have you ever been criticized 6 by anyone at Eli Lilly and Company for forgetting 7 something? 8 A. Not to my recollection. 9 Q. Have you ever made known to 10 any of your colleagues at Lilly that you have a 11 memory problem? 12 A. I have never stated to my 13 colleagues that I have a memory problem, no. 14 Q. Have you ever made known to 15 them that you have adult attention deficit 16 disorder? 17 A. I'm not sure that I have adult 18 attention deficit disorder. 19 Q. Or been treated for that and 20 taken Ritalin for it? 21 A. I don't recall. 22 Q. Well, do you deny that you 23 have? 24 A. I know I have joked with my Page 452 1 colleagues that I have an attention deficit 2 disorder or a mild -- I wonder about that. That 3 has come up in conversations because I have a 4 child with some disabilities, and when one has a 5 child with disabilities, one looks to get one's 6 arms around what may be the problem. And, so, I 7 have thought long and hard about that, and I 8 questioned that as to whether my son may have 9 attention deficit disorder. I'm not sure what's 10 wrong with him. 11 Q. Well -- 12 A. And, so, therefore it's come 13 up in -- 14 Q. I'm talking about you, Doctor. 15 A. Because there's familial cases 16 to some extent with an attention deficit 17 disorder, and it tends to be a male predominant 18 disorder. In sharing some of the angst that I 19 feel relative to my son, I've wondered aloud with 20 my colleagues in conversations as to whether he 21 doesn't come by it honestly. 22 Q. But I think you said you 23 referred to it in a joking manner with your 24 colleagues. Page 453 1 A. Sometimes when I look a little 2 bit disorganized, I'll say it's just my attention 3 deficit disorder. 4 Q. Have you ever been criticized 5 by any of your colleagues for memory problems? 6 A. It's ironic because I think 7 for the most part I've only received compliments 8 for my memory. 9 Q. Well, have you received any 10 compliments for your memory in connection with 11 this conversation that occurred where all -- with 12 the medical examiner where all you can remember 13 is a statement about Scientologists? 14 MR. MYERS: Let me object to the form. 15 That's an argumentative question, Paul. Go on, 16 Doctor, answer that question. 17 A. To be very frank, this is the 18 first time I've had that conversation about what 19 my recollection was relative to that particular 20 phone call. 21 Q. Have you ever received any 22 criticism because of a selective memory? And 23 I'll exclude your ex-wife from that question. 24 A. That's the only person I Page 454 1 recall that ever made that claim, apart from my 2 own self-criticism. 3 Q. Is this marriage that recently 4 ended in divorce the only marriage that you have 5 had, Doctor? 6 A. Yes, sir. 7 MR. MYERS: Let's take a break, Paul, 8 it's about 2:30. 9 (A SHORT RECESS WAS TAKEN.) 10 Q. (BY MR. SMITH) Were there any 11 formal meetings held by those of you who were 12 investigating the issue of Mister Wesbecker's 13 conduct and his ingestion of Prozac? 14 A. As best I recall we tried to 15 obtain as much information as possible relative 16 to the times that he had taken Prozac, as best I 17 recall there was an earlier point in time where 18 he had taken the medication. We tried to 19 establish the duration of that treatment, what 20 the benefits may have been and we tried to obtain 21 information with the most current prescribing of 22 Prozac, as I recollect. 23 Q. Did you determine that in fact 24 Prozac was on board as you have described? Page 455 1 A. As I recall, Mister Wesbecker 2 did have detectable levels of Fluoxetine 3 para-metabolite at the time of his post. 4 Q. And do you remember what those 5 levels were at pose? 6 A. I have a vague recollection 7 that the combined levels were on the order of 8 seven hundred, eight hundred nanograms per ML. 9 Q. Of Fluoxetine? 10 A. And metabolite, as I 11 recollect. 12 Q. And that the normal range 13 expected is between one hundred and three 14 hundred? 15 A. What has been seen most often 16 of the parent compound, as I recollect, would be 17 in the range of one to three hundred. Then one 18 would have to add, in addition, the levels of the 19 metabolite. 20 Q. What are the normal expected 21 ranges of the metabolite? 22 A. Of the metabolite 23 specifically? 24 Q. Yes. Page 456 1 A. As best I can recollect, I 2 have sort of combined the two, so I want to say 3 two hundred to five hundred is my best 4 recollection. So it would be another one hundred 5 to two hundred, possibly, and somewhere in that 6 range. 7 Q. So was it your impression that 8 he had high levels of Prozac and its metabolite 9 found in his blood, average levels or low levels? 10 A. I don't recall if that sample 11 was taken from the cardiac chamber at the time of 12 the post. 13 Q. It was. 14 A. If it was, then there have 15 been reports that those levels are much higher 16 than would have been present in the blood itself. 17 Q. So it was a high level? 18 A. In the cardiac chamber, it was -- 19 it would be on the high side, but that would not 20 be reflective of what was actually in the 21 peripheral blood. 22 Q. You mean working in the 23 serotonin system? 24 A. That would have been in the Page 457 1 blood that profuses the tissues, including the 2 brain. 3 Q. Would there be less levels 4 expected in the blood in the brain versus the 5 blood in the heart muscle itself or in the heart 6 chambers? 7 A. Postmortem? 8 Q. Yes. 9 A. Yes. 10 Q. Why? 11 A. Because as I understand it, 12 there's some leaching of the drug into the 13 cardiac chamber at the time of death. 14 Q. When was that discovered? 15 A. I don't recall. 16 Q. Is that a usual or an unusual 17 phenomena to find with a drug? 18 A. With a drug? 19 Q. Yes. 20 A. This is not my area of 21 expertise, but my understanding would be that 22 that's not unusual, necessarily, that such has 23 been reported with other compounds. 24 Q. That drugs will leach into Page 458 1 higher concentrations in the cardiac chamber than 2 in the brain? 3 A. That's my understanding. 4 Q. Well, is there higher 5 concentrations in the heart muscle -- higher 6 concentrations of blood in the heart muscle than 7 in the brain tissue? 8 A. I'm sorry, let me clarify what 9 I'm referring to. What I'm referring to is that 10 my understanding is that the levels that one 11 finds at postmortem, which most examiners, 12 because of the difficulty in accessing blood from 13 the peripheral circulation, will take a cardiac 14 chamber sample. It is my understanding that the 15 levels that one would find in a cardiac chamber 16 sample at post would be higher than what would 17 have actually been there while the patient was 18 alive, in peripheral circulation. How that 19 translates into levels within the central nervous 20 system and the brain tissue itself, apart from 21 the peripheral circulation, I can't be sure. 22 Q. Were there notes -- have you 23 ever seen any notes made by anybody at Eli Lilly 24 and Company in connection with this phone Page 459 1 conversation with the medical examiner? 2 A. I have a vague recollection 3 that maybe there was some communication that may 4 have been distributed, but I can't be sure of 5 that. 6 Q. You mean communication 7 distributed where? 8 A. To within medical, probably 9 within legal, if it occurred at all. It's a 10 vague recollection. 11 Q. But those would have been the 12 notes that you found -- those would have been 13 notes that would have been findings from a 14 medical component concerning medical issues, 15 would it not? 16 A. As I recollect, that would 17 have been relative to the conversation that was 18 had with the medical examiner relative to some 19 medical findings in all likelihood. 20 Q. All right. Do you recall who 21 the author of those notes was? 22 A. I do not. 23 Q. All right. Was there any 24 information obtained concerning concomitant Page 460 1 medications that Mister Wesbecker might have been 2 taking? 3 A. I have a vague recollection 4 that there may have been additional medications, 5 but I cannot recall specifics. 6 Q. Do you specifically recall 7 whether the postmortem examination indicated any 8 other levels of any other medications on board? 9 A. I don't recall. 10 Q. Well, do you think you would 11 have recalled had that been the case? 12 A. Not necessarily, it's been a 13 very long time. 14 Q. Don't you think you would 15 probably recall had there been any other 16 psychotropic medications, psychoactive 17 medications that he would have been taking that 18 would have accounted in part for this? 19 A. I would like to think I would 20 remember those, but I don't recollect 21 specifically, and I'm not sure that not having 22 reviewed that for a long period of time, that 23 that would be something that I would recall at 24 this time. Page 461 1 Q. Well, were there to be illegal 2 drugs such as cocaine, speed, amphetamines or 3 something of that, that would lead you to the 4 conclusion that this conduct and this tragedy was 5 caused by ingestion of some other medication at 6 the time, that would have been something that you 7 would remember certainly? 8 A. If there was some substance, 9 as you mentioned, and you're talking primarily 10 about substance of abuse, that does not 11 necessarily mean that those substances would have 12 been causally related to the events which 13 occurred. 14 Q. I understand, but that would 15 be something that certainly if you were doing an 16 investigation of any issue such as this would 17 have been relevant to the inquiry, would they 18 not? 19 A. Yes, sir. 20 Q. Because individuals using 21 cocaine, using amphetamines, or abusing those 22 drugs, it is well known that they have a tendency 23 to act in an irrational, violent and aggressive 24 manner, do they not? Page 462 1 A. Those events have been 2 reported. What the percentage of patients who 3 may be abusing those substances are who do indeed 4 manifest that activity is unknown, and would not 5 address the notion of relatedness. 6 Q. Well, as we sit here today, 7 you don't know of any illegal or abusive type 8 medications that Mister Wesbecker was using at 9 the time that would account for his conduct? 10 A. I don't recall that to be the 11 case, that he was abusing substances typically 12 associated with abuse. 13 Q. Did you make any other calls 14 to anybody in Louisville other than the medical 15 examiner, Doctor Heiligenstein? 16 A. I did not place the call to 17 the medical examiner. To the best of my 18 knowledge, I do not recall that I placed calls to 19 anyone in the greater Louisville area at that 20 time. 21 Q. At any time? 22 A. Not that I recall. 23 Q. Did you ever talk to the 24 physician who prescribed Prozac for Mister Page 463 1 Wesbecker yourself? 2 A. I don't recall that I did. 3 Q. Do you know of anybody that 4 did, at Lilly? 5 A. I have a vague recollection 6 that someone spoke with him. 7 Q. Do you recall any information 8 that might have been gleaned from that physician? 9 A. I do not recall the specifics, 10 if there was information. 11 Q. Were you aware in September of 12 1989 whether or not there had been any reports of 13 violent aggressive behavior in connection with 14 Prozac in the past, prior to September, 1989? 15 A. You're not specifically -- 16 you're specifically referring to any kind of 17 violent behavior that did not necessarily result 18 in the death of someone? 19 Q. Violent aggressive behavior in 20 any manner. 21 A. It all gets very muddled 22 because I reviewed some of the post-marketing 23 reports or all the post-marketing reports that we 24 pulled from the analysis, and I have a vague Page 464 1 recollection that I may have signed off on one 2 such report. 3 Q. Of violent aggressive behavior 4 in connection with Prozac usage? 5 A. In a patient that was 6 supposedly taking Prozac. 7 Q. Was that in a clinical trial 8 or a post-marketing experience? 9 A. As I recollect, that was 10 post-marketing. 11 Q. And what was your 12 determination in connection with the causality of 13 that instance? 14 A. It's so vague, I would have to 15 see the original report. 16 Q. How would we go about finding 17 that report? 18 A. My sense is that that report 19 was one that I reviewed earlier today in one of 20 the exhibits that you and your colleague 21 presented me. 22 Q. Well, why don't you take a 23 look through the exhibits. I don't know that 24 we've given you anything other than the exhibits. Page 465 1 A. The one that I recollect 2 reviewing, if I did, I'm not sure, but again I 3 framed this in the context that I reviewed these 4 on a number of occasions over the course of doing 5 the analysis such that it may be a miscall on my 6 part, but the one that seems to stick in my mind 7 as possibly one that I signed off on would be 8 report U.S. '89. 9 Q. What are you looking at, 10 Doctor? 11 A. I'm sorry, this is Exhibit 5 12 on the first page there. And it would be the 13 fourth report on the line listing U.S. report 14 number eight nine zero nine zero zero one zero 15 eight. I am not sure that that report occurred 16 prior to or after the Wesbecker incident. It was 17 reported in September of '89. 18 Q. Are you talking about the 19 forty-five year old female report of hostility 20 that had been on Prozac, twenty milligrams, for 21 four months and who attacked her sixteen year old 22 son? 23 A. That's correct. 24 Q. And you're saying that you Page 466 1 think that that report may have been in existence 2 at the time of the Wesbecker situation? 3 A. I think I would have to go 4 back to your original question. I think you've 5 now reframed the question. As I recall, you 6 asked whether I had specifically signed off or 7 had recollection for signing off on any such 8 reports of violence or aggression. 9 Q. I thought -- the source of my 10 question was what you had said earlier, that in 11 determining causality with respect to whether or 12 not Fluoxetine was involved in a reported adverse 13 event, you needed to know whether or not this 14 particular adverse event had been reported in 15 connection with Fluoxetine use in the past. Do 16 you recall telling me that? 17 A. Could you repeat that? 18 (THE COURT REPORTER READ BACK THE 19 REQUESTED TESTIMONY.) 20 A. I don't understand that 21 question, could you rephrase it for me, please? 22 Q. Well, earlier this afternoon 23 we had gone over factors that you considered in 24 making the determination with respect to whether Page 467 1 or not a particular adverse event was caused by 2 Fluoxetine, Prozac, use. And it's my 3 recollection that you told me something that was 4 of significance to you in making that inquiry was 5 whether or not there had been previous reports of 6 that particular adverse event in connection with 7 Prozac use. Isn't that correct, that you told me 8 that? 9 A. Yes, I believe that captures 10 the essence of what I was communicating about one 11 element of that. 12 Q. And my question was, is at the 13 time you were investigating the Wesbecker 14 situation, did you make any search or did you 15 make any inquiry concerning whether or not 16 violence and aggression had been reported in 17 connection with Fluoxetine-Prozac use before 18 that? 19 A. As I understand the question, 20 you're asking whether at the time we learned that 21 the Wesbecker occurrence -- 22 Q. Or when you were investigating 23 it shortly thereafter. 24 A. Whether we embarked upon a Page 468 1 search of prior post-marketing reports that would 2 have detailed other possible incidents of 3 violence and aggression -- violence and 4 aggression while someone was taking Prozac. 5 Q. No, not really. Did you know 6 at the time or had it been reported to you, and 7 did you know it at the time that it was reported 8 to you, the Wesbecker situation, that there had 9 been -- whether or not there had been previous 10 instances of violence and aggression reported in 11 connection with Prozac use? 12 A. To the best of my 13 recollection, this patient I just mentioned would 14 be the one patient that I might have been aware 15 of had I been the one to review that particular 16 adverse event. 17 Q. Do you know whether or not 18 with respect to that patient, a 1639 was filed? 19 I guess for sure there was if there's a number. 20 A. These have all been filed as 21 1639s here. 22 Q. And was there a determination 23 made by you concerning causality in that instance 24 of violence and aggression with respect to Page 469 1 whether or not that instance of violence and 2 aggression was caused by the use of Prozac? 3 A. That would have depended on 4 whether the event would have been flagged as 5 severe as based upon the reporting guidelines. 6 Then, if it's severe, then one assigns 7 expectancy, and subsequently, depending upon that 8 assignment, would assign causality. 9 Q. My question is simply did you 10 assign causality? 11 A. I don't recall. 12 Q. Did you have an opinion at the 13 time that you were investigating the Wesbecker 14 incident whether or not Prozac could cause 15 violent and aggressive behavior? 16 A. To the best of my 17 recollection, at the time of the Wesbecker 18 incident, my opinion would be that there would be 19 no causal relationship between Fluoxetine and the 20 occurrence of aggressive violent behavior. 21 Q. How long had it been prior to 22 the Wesbecker incident that you were of the 23 opinion that there was no causal relationship 24 between Fluoxetine and violent aggressive Page 470 1 behavior? 2 A. I can't say how long 3 specifically. I can speak from my experience in 4 working with impulsive and aggressive 5 individuals, and with depressed individuals, as 6 well, to have a sense that frequently those 7 manifestations of violence were a component of 8 the core illness or possibly related to an 9 intercurring life event. 10 Q. Let me see if I understand. 11 At the time you began your investigation in 12 connection with whether or not Fluoxetine was 13 causally related to the tragedy in Louisville, 14 Kentucky, you were of the opinion that Fluoxetine 15 had no causal relationship with violent and 16 aggressive behavior, is that correct? 17 A. In my estimation, yes. 18 Q. All right. And you had held 19 that opinion for some time prior to the Wesbecker 20 incident, isn't that correct? 21 A. Yes, that's correct. 22 Q. And how long is it that you 23 are saying you had that opinion? 24 A. I think that opinion evolved Page 471 1 over the course of years that I was in training 2 and in private practice, as well as at the 3 university-based setting. 4 Q. Would it have begun in your 5 medical school years? 6 A. I don't think so. 7 Q. By the time you became Board 8 certified as a psychiatrist? 9 A. I think that would be a fair 10 assessment. 11 Q. All right. That was when? 12 A. I'm estimating that I was 13 certified in psychiatry in 1982 or 1983. 14 Q. Well, Doctor, maybe I'm a 15 little confused. How could you hold the opinion 16 that Fluoxetine was not associated with violence 17 and aggression in 1982 and 1983 when Fluoxetine 18 wasn't even available for the public until 19 December, 1987? 20 A. I misunderstood the question, 21 so I misresponded. I was reflecting on the 22 totality of my experience relative to the 23 occurrence of such events in the life of a 24 patient, regardless of whether he or she was Page 472 1 taking an antidepressant or any other medication, 2 and my sense of relatedness evolved prior to my 3 work with Fluoxetine. 4 Q. Okay. Well, let's put it this 5 way, then, and correct me if I'm wrong, Doctor. 6 Would it be accurate to say that at the time you 7 became Board certified as a psychiatrist, that 8 you were of the opinion that violence and 9 aggression were part of the core illnesses of 10 depression and other mental disorders? 11 A. No. For clarification, I 12 would have held that such aggression could occur 13 in the context of such illness, but all such 14 behaviors could not be explained on the basis of 15 mental illness. 16 Q. All right. So you knew from 17 your training that some violent and aggressive 18 behavior could be explained because an individual 19 was depressed, but not all violent and aggressive 20 behavior could be explained as related to an 21 individual's depression? 22 A. That's correct. May I 23 clarify? 24 Q. Certainly. Page 473 1 A. What I'm trying to capture 2 here is that I believe there are criminal 3 behaviors that are engaged in by individuals 4 which include violence towards others which are 5 not necessarily reflective of any mental illness, 6 but rather just criminality. 7 Q. Do you believe some people are 8 born evil? 9 A. That's a heavy philosophical 10 question. No, I do not. 11 Q. Do you believe that some 12 people are born with a criminal disposition? 13 A. I don't think I hold that. 14 Q. Do you believe that some 15 people have as part of their born makeup a 16 predisposition toward violence or violence 17 towards others? 18 A. I'll give you the best 19 possible answer that I can give, given I think 20 that's a very interesting and complex question. 21 No, I don't believe that individuals are born 22 with a propensity towards violence, towards 23 others. 24 Q. Do you believe that Page 474 1 individuals are born with a propensity to harm 2 themselves? 3 A. Let me respond, because prior 4 to asking questions a light clicked off in my 5 head relative to the earlier responses, and if I 6 may, I'll come back to the other. I'm not -- we 7 do not know enough about criminality in my 8 estimate, I'm not someone who has focused in my 9 career on the criminal individual as a primary 10 area of interest. When I provided those opinions 11 to you, that's my sense, but I would not -- I 12 would offer that a thorough study of such 13 criminal behavior -- I would not exclude that 14 there could not be some association that might be 15 uncovered in terms of a genetic predisposition. 16 I'm not aware that such a genetic predisposition 17 exists. I am aware that there are disorders, 18 mental disorders, in which untreated the 19 individual may engage in harmful activities 20 towards another. 21 Q. Is depression one of those 22 mental disorders? 23 A. I think that within the broad 24 construct of depression, there is some Page 475 1 information to suggest that or that indicates 2 that such individuals are certainly more likely 3 to harm themselves, and that they may be at some 4 increased risk for other injurious behavior. 5 Q. You mean injury to others? 6 A. Yes, sir. 7 Q. Is that why you say or why you 8 said that violence and aggression are part of the 9 core illness of depression? 10 A. I think what I would like to 11 say is that individuals who experience depression 12 may be at some greater risk of other-directed 13 violence, as well as self-directed violence, so 14 that it would in fact be more likely to occur in 15 an untreated individual than a treated 16 individual. 17 Q. Do you know of any scientific 18 article that's been published that supports such 19 a theory in connection with violence or 20 aggression towards others? 21 A. I do not recall any specific, 22 there may be some that exist. 23 Q. Are you saying that there are 24 certainly some that exist? Page 476 1 A. I'm trying to recall if there 2 are any large epidemiological surveys. I don't 3 recall offhand, but as I recall there are some, 4 there's some data to suggest that is indeed the 5 case. I cannot tell you specifically where to 6 find it. 7 Q. You say there is data that 8 supports the proposition that depressed 9 individuals are more likely to commit violence 10 and aggressions towards others, is that your 11 statement here today, Doctor? 12 A. What I'm saying is that there 13 may be some data that suggests that individuals 14 who suffer from depression are at some increased 15 risk for other directed violence. 16 Q. Is aggravation reaction a 17 psychiatric term? 18 A. No, it's not, to my knowledge. 19 Q. Why was it used as a key in 20 your search for violent aggressive events? 21 A. In an effort to be inclusive. 22 And I'm not sure what one means by aggravation 23 reaction other than to take it literally. In our 24 estimation, there may have been such an event Page 477 1 that might have included -- an event that might 2 have been tracked or coded to this particular 3 event term. 4 Q. Is aggravation reaction 5 normally associated with depression? 6 A. I don't know how to assign -- 7 I don't know how to define aggravation reaction. 8 If you're saying do people with aggression become 9 irritable and dysphoric, and is that aggravation, 10 then I would say if that's the way I define it, 11 yes. 12 Q. I'm just using as a definition -- 13 I think that's your term, isn't it, Doctor, 14 aggravation reaction here on Exhibit 1? 15 MR. MYERS: Hold on. Let me object to 16 the form in the use of his term because that's 17 not been the testimony. But answer the question 18 if you can, Doctor. 19 A. Well, that's exactly what I 20 would say, it's not my term. It's a term that 21 was listed in a dictionary to which events would 22 have been coded. 23 Q. Well, that -- 24 MR. MYERS: Wait a minute, let him Page 478 1 finish, Paul. 2 MR. SMITH: Calm dawn, I'm going to. 3 Don't have an aggravation reaction on us right 4 here, Larry. 5 MR. MYERS: I'll do my best. 6 A. Embedded in that, I tried, I 7 hope, to convey to a sense I have that as I would 8 speculate about what that meant, because I don't 9 know what it meant to the people who prepared 10 that particular dictionary, that it might include 11 some irritability, dysphoria, perhaps even some 12 hostility. 13 Q. Didn't it come from the ELECT 14 dictionary published by your employer, Eli Lilly 15 and Company, Doctor Heiligenstein? 16 A. It came from that dictionary. 17 With whom that dictionary was or who prepared 18 that dictionary, and whether it was any 19 additional players, I'm not sure. 20 Q. Well, it's the Eli Lilly event 21 classification term dictionary, isn't it? 22 A. Yes, sir. 23 Q. That's the title, you can see 24 it from here where I'm sitting, can't you? Page 479 1 A. I can see it, yes, sir. 2 Q. And it's got Lilly's trademark 3 or insignia or logo on it on the bottom, doesn't 4 it? 5 A. That's correct. 6 Q. And it's got Lilly Research 7 Laboratories written there on the bottom of it, 8 doesn't it? 9 A. That's correct. 10 Q. And it gives an Indianapolis, 11 Indiana and a zip code, doesn't it? 12 A. Yes, sir. 13 Q. And that's the source of the 14 term aggravation reaction, isn't it? 15 A. That's correct. 16 Q. Lilly's dictionary. 17 A. Again, I'm uncertain as to who 18 prepared that dictionary. As I recall, with some 19 of those dictionary preparations, there were -- 20 may have been some networking in our regulatory 21 group to the FDA, for instance. 22 Q. Well, you picked the term from 23 the dictionary, didn't you? 24 A. Yes, sir, in collaboration Page 480 1 with colleagues. 2 Q. And are you saying that the 3 term aggravation reaction is some junk term 4 that's not descriptive of anything in psychiatric 5 experience? 6 MR. MYERS: Let me object to the form 7 of the question to the extent you're trying to 8 characterize what he says, and that is a gross 9 mischaracterization. You can answer that 10 question if you can. 11 A. Can you read the question 12 back, please? 13 (THE COURT REPORTER READ BACK THE 14 REQUESTED TESTIMONY.) 15 A. No, I'm not saying that. I'm 16 saying I don't know how that term was defined in 17 the eyes of the individuals, be they within Lilly 18 or outside of Lilly, as to how that term refers 19 to or what that term really defines for those who 20 incorporated that into the dictionary. 21 Q. So in going about publishing 22 this article, you used the term used by Lilly in 23 Lilly's dictionary, but that you don't really 24 know how to define, is that correct? Page 481 1 A. As I recall, in the dictionary 2 there are some synonym terms, and there may have 3 been something within those synonym terms that 4 would have been -- which would allow that to be 5 elaborated upon. In any case, as I, as a 6 physician responsible for monitoring that, would 7 say gee, is it possible that someone could have 8 assigned such a term to someone who may have 9 engaged in other-directed violence. 10 Q. Let's see if somebody may have 11 done that by looking at Lilly's own 12 classification of synonym terms. The ELECT 13 classification of aggravation reaction is on the 14 left-hand column, isn't it, Doctor? 15 A. Yes. 16 Q. And the synonym term is 17 aggravation reaction, isn't it? 18 A. That's correct. 19 Q. There are no other synonym 20 terms listed, are there? 21 A. There are not. 22 Q. Is aggravation reaction 23 without any synonym terms, correct? 24 A. That's correct. Page 482 1 Q. Okay. So does that import 2 your -- impact your answer, that there may be 3 some synonym terms that were being used that you 4 were looking for to pick up? 5 A. It does impact it, and it 6 impacts it in such a way that I would still have 7 included that term in the search of the clinical 8 trial -- post-marketing -- I'm sorry, 9 post-marketing events, in an effort to be as 10 inclusive as possible. 11 Q. But you can't define it? 12 A. I define it in my own terms, 13 as to what it would mean to me. 14 Q. Okay. Even though the Lilly 15 ELECT dictionary can't give a synonym for 16 aggravation reaction, can you give a synonym for 17 aggravation reaction? 18 A. The synonym that comes to my 19 mind is -- it's more of a definition, but it 20 would be irritability, slash, dysphoria that may 21 occur in response to some life event. 22 Q. Why didn't you include your 23 irritability/dysphoria in the terms you reviewed? 24 MR. MYERS: Let me object to the form. Page 483 1 Assuming there are such terms, I don't know 2 whether there are or not. 3 A. That's what I was going to say 4 is that I'm not sure. 5 MR. MYERS: Dive on top of that thing. 6 Q. Go ahead and complete your 7 answer. 8 A. I was just saying I wasn't 9 sure whether those terms might not have mapped to 10 another event term that may have been a component 11 of this. 12 Q. While she's looking, is acute 13 brain syndrome normally seen in depressed 14 individuals? 15 A. No, it's not. 16 Q. Doctor, there's a cross 17 reference in here that mentioned irritability, 18 but it's mentioned as a synonym, as you used it, 19 but the ELECT term is nervousness, isn't it? 20 A. That's correct. 21 Q. Is nervousness an item that 22 you looked for or listed in the ELECT terms that 23 you were going to review for aggressive violent 24 behavior? Page 484 1 A. No, it was not. 2 Q. Did you search the DEN data 3 base for any terms other than the terms listed on 4 Exhibit 1, the DEN data base? 5 A. I do not recall that we did. 6 Q. Not the -- well, did you 7 search the clinical trial data base for any terms 8 other than those terms listed in Exhibit 1? 9 MS. ZETTLER: And anti-social 10 reaction. 11 Q. Yes, anti-social reaction on 12 Exhibit 1. 13 A. I do not recall that we did. 14 Q. Why? 15 A. Again, as this process was 16 embarked upon, I and a colleague of mine selected 17 those terms that we thought would most likely 18 capture an event that might have embedded within 19 it some possibilities of -- not within the event, 20 but might have been used as an ELECT term for an 21 event of aggressivity. 22 Q. But they really don't, do 23 they, Doctor? 24 MR. MYERS: Let me object to the form. Page 485 1 They don't do what? 2 Q. Capture aggressive violent 3 terms. 4 A. I think they do. And the 5 reason I say that, although one would prefer to 6 have something more precise, and now we do, the -- 7 it doesn't negate the value of this particular 8 search, and as your colleague mentioned, over a 9 thousand such 1639s were reviewed in this process 10 in an effort to be as thorough as possible. And 11 in terms of -- the yield was very low, and it 12 leads me to conclude that to the time of 13 Wesbecker, there were relatively few such events 14 reported to us, and as reflected by the yield 15 from this particular -- 16 MS. ZETTLER: I'm going to object to 17 his answer as a mischaracterizing my earlier 18 question. 19 MR. MYERS: I thought he was giving 20 you credit for saying something. 21 Q. Do you think that the data -- 22 do you think that the scientific research that 23 you did and the scientific paper you wrote that's 24 reflected by Exhibit 3, "Fluoxetine Not Page 486 1 Associated With Increased Violence Or Aggression 2 In Controlled Clinical Trials," is a good 3 scientific work? 4 A. I do. 5 Q. Well, let's see about that. 6 That work did not involve all the data that you 7 had on the subject in your own data bases, did 8 it? 9 A. I don't know what you're 10 referring to. 11 Q. Well, it didn't include any 12 statistics in connection with the post-marketing 13 experience, did it? 14 A. It did not. 15 Q. And you had that available in 16 your DEN system at the time, didn't you? 17 A. That's correct. 18 Q. It didn't reflect 19 post-marketing reports of violence or aggression, 20 did it? 21 A. It did not. 22 Q. It didn't analyze reports of 23 violence and aggression that were made by 24 physicians in the field, did it? Page 487 1 A. It did not. The subject was a 2 statistical analysis because such analysis would 3 not be possible in my estimation. 4 Q. It wasn't done, was it? 5 A. No. I'm not sure it could be 6 done. 7 Q. This work reflects only a 8 limited amount of data, doesn't it? 9 A. It reflects the double-blind 10 placebo comparator controlled -- 11 MR. MYERS: Let him finish, please. 12 A. -- studies that were completed 13 at the time that the event became known to us. 14 Q. Which was a limited amount of 15 data that you had at the time? 16 A. Limited and the most 17 scientific. 18 MS. ZETTLER: We object to that answer 19 as being not responsive to the question asked. 20 MR. MYERS: You just don't like the 21 answer. 22 Q. My question was -- 23 MR. SMITH: I object to your side-bar 24 remark, Counsel. Page 488 1 Q. The question was, it's limited 2 in the data -- you had more data than is 3 reflected in the paper, didn't you? 4 A. We did not have more data that 5 would be subject to analysis. 6 Q. You had more data, didn't you? 7 MR. MYERS: Let me object to the form, 8 more data than what? 9 MR. SMITH: More data than is 10 mentioned in this publication. 11 A. If you're referring to 12 specific reports in our DEN data base from 13 spontaneous post-marketing reporting, yes, that 14 information was there. 15 Q. It didn't mention, did it, 16 that you had reviewed over a thousand reports in 17 your DEN data base of possibilities of violent 18 and aggressive action, did it? 19 A. It did not -- no, that's, I 20 think, an inaccurate characterization of that 21 initial exercise. I'm not saying that -- we did 22 not expect that the net that we cast with these 23 multiple terms would necessarily capture a 24 multitude of events. We didn't know what it Page 489 1 would capture, and we didn't expect that many of 2 those reports would reflect other directed 3 violence. 4 Q. You had -- 5 MR. MYERS: Let him finish. 6 A. So that for you to 7 characterize that as possible whatever, I think 8 is something of a mischaracterization. 9 Q. See, I think it's a 10 mischaracterization that you would conclude that 11 you have -- that there would be fourteen reports 12 of violent aggressive behavior in a population of 13 five thousand individuals, and come to the 14 conclusion based on that that Fluoxetine does not 15 cause aggressive behavior. Don't you agree that 16 that's a mischaracterization? 17 MR. MYERS: Before he answers, let me 18 object to the form of the question, and the 19 question is highly argumentative, it 20 mischaracterizes his testimony and I'm going to 21 ask you one time, Paul, to lower your voice, and 22 don't raise your voice to me or to the witness, 23 you don't need to do that. 24 MS. ZETTLER: He's not raising his Page 490 1 voice. 2 MR. MYERS: If you can answer the 3 question, Doctor, go ahead. 4 MS. ZETTLER: Let the the record 5 reflect that Larry mischaracterized Paul's tone 6 of voice. 7 MR. MYERS: We can check it against 8 the various tapes -- 9 (DISCUSSION OFF THE RECORD.) 10 MR. MYERS: Paul, go on to something 11 else. Doctor, if you can recall that last 12 question, answer it. If you can't, have her read 13 it back. 14 THE WITNESS: I would prefer that she 15 read it back. 16 (THE COURT REPORTER READ BACK THE 17 REQUESTED TESTIMONY.) 18 A. I do not. 19 Q. Well, take your table that is 20 contained in Exhibit 3 and help me. 21 A. Exhibit 3 has a table? 22 Q. Yes. 23 A. I don't think my copy has that 24 table, sir, let me take a look. Page 491 1 MR. MYERS: Are you looking for the 2 actual paper possibly or publication? 3 Q. While you're looking, your 4 original paper had some tables in it, didn't it? 5 A. The published manuscript. 6 (PLAINTIFFS' EXHIBIT NO. 7 WAS 7 MARKED FOR IDENTIFICATION AND 8 RECEIVED IN EVIDENCE.) 9 Q. Look at Exhibit 6 which 10 appears to be a published copy -- 7, and see if 11 that's got some tables in it. 12 A. To my knowledge, this is not 13 the published manuscript. It's not a -- it's not 14 the final manuscript, as far as I know, but let's 15 take a look here for the tables. 16 Q. Go with me to table one. What 17 does table one reflect? 18 A. Table one is the incidence of 19 aggression cluster events in double-blind placebo 20 controlled clinical trials, parens, all 21 indications, end parens. 22 Q. If you look at that, it looks 23 like there were two thousand six hundred and 24 fifteen people on Fluoxetine in that clinical Page 492 1 trial, correct? 2 A. That's correct. 3 Q. And one thousand three hundred 4 and seventy-seven people on placebo in that 5 clinical trial, correct? 6 A. That's correct. 7 Q. If you'll add that up, that 8 totals to three thousand nine hundred and 9 ninety-two people, doesn't it? 10 A. Yes, sir. 11 Q. Of those, four people on 12 Fluoxetine experienced violent aggressive 13 behavior, correct? 14 A. Four people had events that 15 fell within the aggression cluster. 16 Q. Which is what you're defining 17 as aggressive violent behavior, isn't it? 18 A. No, we did not know that those 19 necessarily would contain within them instances 20 of other-directed aggression or violence. 21 Q. So maybe not even four of them 22 experienced violent aggressive behavior? 23 A. That's correct. 24 Q. And of the placebo group, Page 493 1 there were nine, correct? 2 A. That's correct. 3 Q. For a total of thirteen people 4 out of three hundred and ninety-two individuals 5 in clinical trials that could have established 6 violent aggressive behavior, correct? 7 A. I think you gave an incorrect 8 number, it was three thousand nine hundred and 9 ninety-two. You just said three ninety-two, so I 10 wanted to -- 11 Q. Three thousand nine hundred 12 and ninety-two. 13 A. Yes, sir. 14 Q. Thirteen out of three thousand 15 three hundred and ninety-two could possibly be in 16 the violent aggressive category? 17 A. Thirteen of those patients 18 were identified through the aggression cluster 19 search. 20 Q. Now go with me to table three, 21 which is analysis of the double-blind trials 22 comparing Fluoxetine with tricyclic 23 antidepressants, isn't it? 24 A. Yes, sir. Page 494 1 Q. In that group, there were four 2 hundred forty-one people that were given Prozac, 3 right? 4 A. That's correct. 5 Q. And none of them fell within 6 any aggression violence cluster, did they? 7 A. That's correct. 8 Q. And of the tricyclics, there 9 were four hundred and forty-five individuals 10 given tricyclics? 11 A. That's correct. 12 Q. And only one of them 13 experienced -- 14 A. That's correct. 15 Q. -- aggressive violent 16 behavior, right? 17 A. That's correct. 18 Q. So out of eight hundred and 19 eighty-six people in that group, only one 20 experienced something that would be of a violent 21 aggressive type cluster? 22 A. In the aggression cluster 23 event, yes. 24 Q. Okay. The next table, table, Page 495 1 what is it, four? 2 A. Yes, sir. 3 Q. Compares Fluoxetine tricyclics 4 and placebos, doesn't it? 5 A. That's correct. 6 Q. And that analyzes three 7 hundred and nine individuals who were on 8 Fluoxetine, right? 9 A. Yes, sir. 10 Q. None of them were found to 11 come up with violent aggressive behavior? 12 A. None of them? 13 Q. Right. 14 A. In response to that again, 15 none were identified with the aggression cluster 16 of events. 17 Q. So they were zeros, weren't 18 they? 19 A. That's correct. 20 Q. Of the placebo group, there 21 wasn't even anybody in the two hundred and 22 ninety-seven people in placebo that experienced 23 anything on the violent aggressive group? 24 A. Patients who fell into that Page 496 1 aggression cluster of events, correct. 2 Q. And those patients, three 3 hundred and eight patients, taking tricyclics, 4 there weren't any either, was there? 5 A. That's correct. 6 Q. So if you add the total of all 7 individuals in that group, those groups listed on 8 those three tables, you get five thousand seven 9 hundred ninety-two people. Would you accept my 10 math? 11 A. I will accept it. 12 Q. All right. And of those five 13 thousand seven hundred and ninety-two people who 14 were in the clinical trials, you only picked up 15 fourteen individuals who might have experienced 16 this violent aggressive cluster that you picked 17 out? 18 A. That's correct. 19 Q. Doctor, has anybody that you 20 know of from Eli Lilly and Company gone to the 21 United States government and taken them these 22 figures and suggested that Prozac be used in the 23 federal penitentiaries? 24 A. No. Page 497 1 Q. I mean with this kind of 2 results, maybe we ought to be giving this to our 3 criminals. Do you think that's an idea? 4 A. In all honesty, I did have a 5 warden from one of the state systems call me with 6 that suggestion. 7 Q. Let's put everybody in prison 8 on Prozac? 9 A. That's what he said. 10 Q. All right. Did you? 11 A. I certainly didn't. 12 Q. Did you pass that on to the 13 marketing end at Eli Lilly and Company? 14 A. No, I did not. 15 Q. Did you give this paper to 16 anybody at marketing in Eli Lilly? 17 A. This particular manuscript? 18 Q. Yes. 19 A. I suspect that it was seen by 20 others outside of medical. 21 Q. Do you know if they ever used 22 it as a marketing tool to sell Prozac to penal 23 institutions? 24 A. I'm not aware of any such Page 498 1 activities. 2 Q. Do you know whether or not 3 anybody has taken these statistics and brought 4 them before a school system to potentially use 5 Prozac to treat violent aggressive children so 6 our schools will work better? 7 A. I'm not aware that such 8 activity occurred. 9 Q. Do you know if anybody has 10 brought these figures up before some city counsel 11 to deal with the problems of crime in the inner 12 cities? 13 A. I'm not aware that that's the 14 case. 15 Q. Did you ever run these figures 16 by any statistician? 17 A. Our internal statistics 18 department has reviewed this. 19 Q. Doctor Dornseif? 20 A. Yes. 21 Q. Did he -- did he question, as 22 far as you know, or that you recall, that these 23 figures are astounding from a statistical 24 standpoint? Page 499 1 A. I don't know that anyone ever 2 used that terminology. 3 Q. I mean these are people in the 4 controlled clinical trials, are they not? 5 A. That's correct. 6 Q. And they're all theoretically 7 individuals who are suffering from depression or 8 suffering from depressive related illnesses, 9 correct? 10 A. This was an analysis across 11 multiple indications. 12 Q. And those other indications 13 have depression as co-morbidity, don't they? 14 A. But not necessarily in those 15 particular trials. I suspect that many of those 16 study patients with depression were excluded. 17 Q. Well, what other indications 18 were reflected by these clinical trials? 19 A. Smoking. 20 Q. Smoking? 21 A. Bulimia. 22 Q. Bulimia. 23 A. Obesity. 24 Q. Obesity. Page 500 1 A. Alcoholism. Actually smoking 2 cessation to be more precise. And those were the 3 indications. 4 Q. Okay. So you had some people 5 even in these controlled clinical trials that 6 they were trying to quit smoking? 7 A. There was a smoking IND, as I 8 recall. 9 Q. And you had some people who 10 were too fat, felt they needed to lose weight? 11 A. There was -- there were 12 obesity trials, yes. 13 Q. And I assume those individuals 14 were on diets or did those obesity trials allow 15 them to pork up in any manner they wanted? 16 A. I don't recall the specifics 17 of the exclusion. 18 Q. In other words did protocols 19 limit the caloric intake that patients could 20 engage in? 21 A. Not that I recall. 22 Q. There were some monitoring of 23 their caloric intake, wasn't there? 24 A. I don't know, I was not Page 501 1 responsible for those studies. 2 Q. Well, you used them in your 3 statistics, didn't you? 4 A. That's correct. 5 Q. Then you had some people that 6 have alcoholism that you -- 7 A. That's correct. 8 Q. People who were trying to quit 9 drinking? 10 A. That's correct. 11 Q. You had people that are trying 12 to quit smoking, you have people that are trying 13 to quit eating, and you have people that are 14 trying to quit drinking, right? 15 A. I'm not sure that the people 16 who were trying to lose weight were necessarily 17 trying to stop eating. I would agree with you 18 that the individuals with problems with alcohol 19 and smoking would have had as a motivation 20 cessation of those particular habits. 21 Q. Well, wouldn't you suspect 22 that in the obesity trials, the individuals who 23 were participating in the obesity trials were 24 concerned about their weight and trying to Page 502 1 eliminate excess weight? 2 A. Yes, sir. 3 Q. And that made up some of these 4 clinical trial groups that you analyzed? 5 A. Yes, sir. 6 Q. And then you analyzed a whole 7 bunch of depressed people, too, three thousand 8 nine hundred -- well, you can't really tell, but 9 the majority of them were depressed people, too, 10 weren't they? 11 A. Yes, sir. 12 Q. Did you question why you only 13 picked up fourteen aggressive violent potential 14 acts in these people? 15 A. Yes, sir. 16 Q. In this almost six thousand 17 people? 18 A. Yes, sir. 19 Q. All right. What scientific 20 explanation do you have for it? 21 A. I don't know that it's 22 necessarily a scientific explanation, but many of 23 these trials were time limited, six and 24 eight-week trials. So therefore, the lack of Page 503 1 occurrence of events that fell into that 2 aggression cluster does not necessarily speak to 3 the occurrence of events in the life of the 4 illness. 5 Q. Okay. That then speaks 6 against the premise that you make in this 7 article, that Fluoxetine is not associated with 8 increased violence or aggression, doesn't it? 9 A. No, it doesn't. 10 Q. That's your opinion? 11 A. In my estimation. 12 Q. Any other explanation as to 13 why you would only catch fourteen instances out 14 of six thousand people? 15 A. Well, there is some suggestion 16 in the scientific literature that would suggest 17 that a compound like Fluoxetine may in fact 18 decrease impulse aggressivity. 19 Q. Do you believe that? 20 A. I think it's very likely. 21 Q. Then why not give this to 22 prisoners? 23 A. That's not my decision. 24 Q. Don't you agree that crime is Page 504 1 a major problem in this country? 2 A. I do. 3 Q. And don't you agree that we 4 need to take whatever measures are necessary to 5 reduce the amount of crime? 6 MR. MYERS: Hold on. Before he 7 answers, Paul, you are getting very far afield, 8 this is not relevant, it's not likely to lead to 9 discovery or relevance or admissible evidence. 10 Where are you going with this? 11 MR. SMITH: I'm going to cross 12 examination. 13 MR. MYERS: Well, you're going to have 14 a little bit more cross examination, and then 15 we're going to shut this part of the testimony 16 down. I mean this is absolutely out in left 17 field. 18 MR. SMITH: That's your opinion. 19 A. Repeat the question. 20 Q. Don't you think we need to 21 take measures to reduce crime in this country? 22 A. Yes, sir. 23 Q. Have you ever suggested to 24 anyone that by virtue of this ability of Prozac Page 505 1 to reduce impulsivity and reduce the amount of 2 violent aggressive behavior that it purportedly 3 has, that it be given to people who are 4 displaying this kind of violent aggressive 5 behavior that's causing crime in our society? 6 A. Like you, I would be very 7 interested in alleviating crime in our society. 8 Unfortunately most crime is premeditated and 9 consequently a compound like this would not 10 likely be of benefit in individuals who are 11 engaging in premeditated criminal behavior. 12 Q. Apparently it was a benefit to 13 these almost six thousand individuals that you 14 picked out of your clinical trial. 15 A. I don't know what their 16 baseline impulsivity aggressivity was. 17 Q. Then how can you make any 18 opinion and how can you write up a paper about 19 the way Fluoxetine reduces their impulsivity and 20 aggression if you don't know anything about what 21 their baseline impulsivity was? 22 MR. MYERS: Before he answers, let me 23 object to the form of the question to the extent 24 you tried to characterize what the paper says. I Page 506 1 think you mischaracterized it. But if you can 2 answer, go ahead. 3 A. That was to be my response, I 4 don't know that that was the focus of the paper. 5 I did not -- this paper was not undertaken as a 6 scientific study to document reduction in 7 impulsivity and aggressivity, but rather the 8 occurrence during double-blind placebo comparator 9 controlled clinical trials. 10 Q. The title of the article is, 11 is it not, "Fluoxetine Not Associated With 12 Increased Violence Or Aggression In Controlled 13 Clinical trials"? 14 A. Yes, sir. 15 Q. Wouldn't that lend -- that 16 lends me to say that you're of the position in 17 this paper that Prozac doesn't cause an increase 18 in violence or aggression. Is that what you're 19 saying? 20 MR. MYERS: Same objection as to form. 21 Go ahead and answer, Doctor. 22 A. I think what the title is 23 intended to communicate is that the occurrence of 24 such events is not increased with violence or Page 507 1 aggression in controlled clinical trials, and one 2 condenses that into a composite statement. I 3 think the conclusions of the study would be the 4 ones that I would focus on in terms of our 5 findings in the study. 6 Q. You mean you think it's not 7 associated with increased violence or aggression? 8 A. That's correct. 9 Q. And you think indeed there's 10 much authority, much support, for the proposition 11 that Prozac reduces violence and aggression, is 12 that correct? 13 A. I didn't say that. I said 14 that there is theoretical speculation which is 15 supported by some studies, not this one, which 16 suggests that selective serotonin uptake 17 inhibition in a sense enhancing serotonergic 18 function would lead to diminished impulsive 19 aggressivity. 20 Q. Didn't help Joseph Wesbecker, 21 did it? He went and blew away twenty people. 22 MR. MYERS: Let me object to the form. 23 That's an argumentative question. It didn't help 24 him in what way, to treat what? Do you Page 508 1 understand the question, Doctor? 2 A. Repeat it, please. 3 Q. It didn't help Joseph 4 Wesbecker, did it, he blew away twenty people? 5 A. I didn't know -- I don't know 6 whether it helped or not, you know, but my sense 7 is that that was a premeditated criminal offense. 8 Q. What made you think it was 9 premeditated, Doctor Heiligenstein? 10 A. As best I recollect, he had 11 guns and a plan of action and made threats. 12 Q. Well, I have guns. 13 MR. MYERS: Are you through? 14 Q. I have guns. The fact that 15 people have guns doesn't mean that they are 16 premeditating using those guns, does it? 17 A. It does mean that they plan to 18 use those guns for some purpose, be it collecting 19 or target shooting or possibly criminal offense. 20 Q. Did you make any investigation 21 to determine whether or not Joseph Wesbecker had 22 the mental capacity to commit premeditated 23 murder? 24 A. Did I make an investigation is Page 509 1 the question? 2 Q. Yes. 3 A. No, I did not. 4 Q. Did you have any facts before 5 you or do you have any facts before you to 6 indicate that Joseph Wesbecker was mentally sane 7 at the time he committed these atrocious acts? 8 A. Could you define mentally 9 sane? 10 Q. In psychiatric terms. 11 MR. MYERS: Before he answers --. 12 Q. You're the psychiatrist, you 13 define it. 14 MR. MYERS: Let me object to the form 15 to the extent that your question and the use of 16 that terminology may imply some sort of legal 17 standard as to sanity or insanity, capacity. 18 Q. I'm using the term that you 19 were using as a psychiatrist. 20 A. It's my opinion that Mister 21 Wesbecker knew what he was doing. 22 Q. Do you have an opinion 23 concerning whether or not he had a mental 24 disorder? Page 510 1 A. I would have an opinion that 2 he did have a mental disorder. 3 Q. And what was that? 4 A. I cannot fully characterize 5 that mental disorder. It appeared to me to be 6 rather complex, and I did not have the 7 opportunity to evaluate him. 8 Q. Then how can you have the 9 opinion that he had a mental disorder or that he 10 knew what he was doing if you can't even describe 11 the complexity of his illness? 12 A. In part, that's based upon 13 information gathering that was undertaken 14 relative to the event, and in addition, on my 15 collective experience. 16 Q. What information did you have 17 concerning his psychiatric condition? 18 A. As I best recollect, there was 19 a rather detailed account of his personal, and to 20 some extent his medical history, that had been 21 published in a Louisville magazine, a monthly 22 magazine, where an investigative reporter had 23 pulled together multiple sources of information, 24 and as I recall, in addition, there was Page 511 1 information regarding contacts that Mister 2 Wesbecker had had with physicians with whom he 3 had consulted. 4 Q. So what was wrong with him 5 from a psychiatric standpoint? 6 A. I can't really say, I didn't -- 7 I would have to rely on that historical 8 information, and again, that could span a 9 spectrum. 10 Q. What spectrum? 11 A. It could span the spectrum 12 from affective disorder to a schizo affective -- 13 schizo type of disorder. I would add that that 14 would not be all inclusive. 15 Q. Well, is Prozac an appropriate 16 psychiatric treatment for an affective disorder? 17 A. Yes, it is. 18 Q. Is Prozac an effective 19 psychiatric treatment for psycho affective 20 disorder -- schizo affective disorder? 21 A. We have not sought that 22 indication, and to my knowledge -- 23 Q. Is it or is it not an 24 effective treatment for that? Page 512 1 A. It may -- it's possible, in my 2 opinion, that it could be efficacious for the 3 affective component of that disorder. 4 Q. Then why didn't Prozac work 5 with Joseph Wesbecker? 6 A. It doesn't work for everybody. 7 MR. MYERS: Let's take a short break. 8 (A SHORT RECESS WAS TAKEN.) 9 Q. Doctor, in reviewing the 10 clinical trials to come to the conclusion of your 11 paper that Fluoxetine is not associated with 12 increased violence or aggression, what scientific 13 basis did you have for excluding the clinical 14 trials run by Eli Lilly outside the United States 15 of America? 16 A. I don't recall the specifics. 17 As I recall, early in the process when we 18 established a priori what the analysis would 19 consist of, we made a decision to focus on the 20 U.S. IND clinical trial data base. 21 Q. My question is why did you 22 make that decision to just focus on the United 23 States? 24 A. I don't recall. Page 513 1 Q. Was there some problem with 2 the clinical trials that were conducted outside 3 the United States? 4 A. Not that I'm aware of. 5 Q. Was there some belief that 6 there might be more or less violent aggressive 7 behavior in individuals living within or without 8 the United States? 9 A. There was not. 10 Q. Was there some belief that the 11 investigators that were conducting clinical 12 trials in the United States were more competent 13 and thorough than those investigators hired by 14 Lilly outside the United States? 15 A. There was not. 16 Q. Was there any difference in 17 the protocols that were used to conduct the 18 clinical trials in the United States than those 19 clinical trials outside the United States? 20 A. There may have been some 21 differences, but they would not have been 22 substantive. 23 Q. It wouldn't have made any 24 difference in your study, would it? Page 514 1 A. No, it would not have. 2 MS. ZETTLER: Did they use the ELECT 3 dictionary outside the United States also? 4 THE WITNESS: I don't recall. 5 MS. ZETTLER: How can we find out 6 whether or not they used the ELECT dictionary 7 outside the United States? 8 THE WITNESS: Who would be that 9 person? 10 MS. ZETTLER: Who would know that? 11 THE WITNESS: I suspect Doctor 12 Talbott. 13 MS. ZETTLER: How about Doctor 14 Beasley, would he know? 15 THE WITNESS: I don't know. 16 Q. Some of these clinical trials 17 that were conducted in the United States were 18 conducted exactly the same outside the United 19 States, weren't they? 20 A. Exactly the same? 21 Q. Yes, according to the same 22 protocol, same dosage, same inclusion and 23 exclusion criteria. 24 A. I can't really answer that Page 515 1 with the degree of accuracy that I would like to. 2 I suspect there would have been some slight 3 differences in some of those protocols when 4 compared to our protocols. How substantive any 5 differences may have been, I don't know. 6 Q. You don't remember any 7 differences in those protocols that cause you to 8 exclude the outside United States clinical trials 9 from your analysis, do you? 10 A. No, sir. 11 Q. The clinical trials that were 12 included in these -- in this analysis involved a 13 controlled population, did they not? 14 A. Are you referring to a select 15 population? 16 Q. Yes. 17 A. Yes, they would have. 18 Q. They were patients that had to 19 meet an inclusion criteria, correct? 20 A. That's correct. 21 Q. And could not be included 22 within a group if they fell as part of an 23 exclusion criteria? 24 A. That's correct. Page 516 1 Q. For instance, people with 2 serious suicidal risk were excluded from all of 3 the outpatient clinical trials, weren't they? 4 A. As best I recollect, that was 5 an exclusion criteria. 6 Q. And people with other 7 psychiatric illnesses were excluded from the 8 clinical trials, were they not? 9 A. There would have been a number 10 of conditions which would have been excluded. 11 Whether that would have been -- would have 12 covered the full scope of psychiatric disorders 13 within each protocol, I cannot be certain. 14 Q. But for sure there were some 15 psychiatric illnesses that were excluded from 16 individuals in the inclusion -- in the clinical 17 trials that are more likely to produce violent 18 and aggressive characteristics, aren't they? 19 A. I'm not sure what diagnostic 20 group you would be referring to. 21 Q. I'm not sure either, but 22 people with schizo affective disorder were 23 excluded from most of the clinical trials, 24 weren't they? Page 517 1 A. Yes, sir, to the best of my 2 knowledge. 3 Q. And people with serious schizo 4 affective disorder are more prone to violence and 5 aggression than individuals not suffering from 6 that disorder, aren't they? 7 A. I don't know that I have seen 8 data to support that that I can recall. 9 Q. Sound reasonable, though, 10 doesn't it? 11 A. Clinically, it sounds 12 reasonable. 13 Q. In fact, in connection with 14 the United States clinical trials, concomitant 15 medications were allowed, were they not? 16 A. I'm sorry? 17 Q. In the clinical trials, 18 concomitant medications were allowed, weren't 19 they? 20 A. I'm not sure which concomitant 21 medications you're referring to. 22 Q. Benzodiazepams for agitation, 23 within the discretion of the investigator. 24 A. In the U.S. clinical trials? Page 518 1 Q. Yes. 2 A. I'm not sure that was the case 3 in all U.S. protocols. 4 Q. Would it be significant to you 5 to know, Doctor, in making an analysis whether or 6 not Fluoxetine was associated with increased 7 violence or aggression that the United States 8 clinical trials allowed the investigators hired 9 by Lilly to administer benzodiazepams to their 10 patients for agitation? 11 A. Would that be of significance? 12 Q. Yes. 13 A. No, I don't think so. 14 Q. Well, if a patient is 15 receiving a tranquilizer, they're less likely to 16 become agitated, aren't they? 17 A. I don't know that one can 18 characterize a benzodiazepine as a tranquilizer. 19 MS. ZETTLER: Chloral hydrate? 20 Q. What is Benzodiazepine? 21 A. Benzodiazepines are compounds 22 that are used for multiple indications, they can 23 be used as a hypnotic, and they can be used as an 24 antianxiety agent. Page 519 1 Q. Reduce anxiety, don't they? 2 A. They have been used for that 3 purpose, yes. 4 Q. And if you reduce anxiety, 5 you're going to reduce agitation, aren't you? 6 A. If agitation is a component of 7 the anxiety, you may very well reduce that to 8 some extent. 9 Q. It's a component in many 10 instances, isn't it, Doctor? 11 A. How do you define many, I'm 12 not sure. 13 Q. However you define many. 14 A. In my experience, a minority 15 of patients with anxiety -- a minority of 16 patients with depression suffer from concomitant 17 anxiety would be identifiable as agitated as 18 well. 19 Q. Doctor, wouldn't a person be 20 less likely to be violent or aggressive if they 21 were being administered Benzodiazepines? 22 A. Not necessarily. 23 Q. But it's likely, isn't it? It 24 may not occur every time, but it's likely that it Page 520 1 will reduce their tendency towards violence or 2 aggression, isn't it? 3 A. I don't know that there's ever 4 been, and I'm not familiar with the literature 5 relative to this, a study which documented that 6 benzodiazepines reduce the aggressivity in 7 individuals who were being treated for depression 8 and/or anxiety or some combination thereof. 9 Q. You just won't agree with me 10 that Benzodiazepines are more likely to result in 11 a patient being less violent or less aggressive, 12 will you? 13 A. I'm saying that's unlikely. 14 Q. Okay. 15 MS. ZETTLER: Is chloral hydrate a 16 Benzodiazepine? 17 THE WITNESS: No. 18 Q. What is chloral hydrate? 19 A. Chloral hydrate is a hypnotic. 20 Q. What is it used for? 21 A. It's used for insomnia. 22 Q. And it makes you go to sleep? 23 A. It's a sleep aid. 24 Q. Hypnotic. Does that mean Page 521 1 you're going to go around in a trance? 2 A. No. 3 Q. What does hypnotic mean in the 4 scientific world? 5 A. In the scientific world it 6 means a medication which would -- well, or an 7 intervention which will allow one to have a 8 reduction in their complaint of insomnia. 9 Q. It makes them less active, 10 doesn't it? 11 A. Less active? 12 Q. Yes. 13 A. Well, if it promotes sleep, 14 when one is asleep they're less active. But in 15 terms of chloral hydrate being used to treat 16 individuals who are -- have disorders of activity 17 levels, no, it's not used for that. 18 Q. But it's used to make people 19 relax, isn't it? 20 A. No. 21 Q. Is it your testimony that 22 chloral hydrate doesn't make individuals more 23 relaxed? 24 A. It's my testimony that chloral Page 522 1 hydrate's indication is for disorders of sleep. 2 Q. I understand that. But 3 doesn't it make patients more relaxed? 4 A. I have not seen any evidence 5 to that effect. 6 Q. What is the brand name that 7 chloral hydrate is usually administered? 8 A. I don't know. 9 Q. You don't know? 10 A. No. 11 Q. If you were going to give me a 12 prescription for chloral hydrate, would you just 13 write chloral hydrate? 14 A. I do not recall that I have 15 ever prescribed chloral hydrate except for 16 youngsters who were going to have an all-night 17 sleep EEG to look at the possibility of a seizure 18 disorder. 19 Q. And when you did that, you did 20 that to relax the patient so they would sleep? 21 A. No, I did that to induce 22 sleep. 23 Q. To induce sleep, the mechanism 24 of chloral hydrate is that it causes the patient Page 523 1 to become more asleep, doesn't it, I mean more 2 relaxed? 3 A. No. My understanding of the 4 mechanism of action, it does act on the central 5 nervous system such that it induces a state of 6 sleep. 7 Q. How does it do that? 8 A. I suspect, and I don't know 9 specifically, so I would be speculating, that it 10 may just slow the EEG and put one -- it would 11 help one move into the stage of EEG activity that 12 is more likely that characteristic of sleep. 13 Q. Does that make the person less 14 active? 15 A. Sleep makes people less 16 active. 17 Q. And moving into that state or 18 going to sleep, doesn't it make them less active? 19 A. As one becomes drowsy, yes, 20 people become less active. 21 Q. If you're drowsy, you're less 22 likely to be violent or aggressive, aren't you? 23 A. I would think so. I don't 24 have any scientific evidence to support that Page 524 1 statement. 2 Q. The clinical trials -- were 3 you aware that the clinical trials allowed for 4 administration of chloral hydrate for sleep? 5 A. Yes, sir. 6 (PLAINTIFF'S EXHIBIT NO. 8 WAS 7 MARKED FOR IDENTIFICATION AND 8 RECEIVED IN EVIDENCE.) 9 Q. While you're looking at that, 10 Doctor, what is Flurazepam? 11 A. Flurazepam, I believe, is 12 Restoril -- no, I can't be sure, I'm sorry. One 13 of those two is Restoril. 14 Q. What is Flurazepam used for? 15 A. It is a hypnotic or to induce 16 sleep. 17 Q. What is Trazodone? 18 A. Trazodone. 19 Q. Trazodon. 20 A. Halcion. 21 Q. Halcion? 22 A. Yes, sir. 23 Q. And Flurazepam is Restoril? 24 A. Flurazepam, as best I Page 525 1 recollect, one of those is Restoril. 2 Q. What is Restoril? 3 A. It's an agent to use to induce 4 sleep. It's indication is for insomnia. 5 Q. Have you had an opportunity to 6 review Exhibit 8? 7 A. I have, sir. 8 (DISCUSSION OFF THE RECORD.) 9 Q. Doctor Atul Pande is who? 10 A. Atul Pande is a research 11 physician in the division of psychopharmacology. 12 Q. And Tina? 13 A. Tina Schlanser or Christine 14 Schlanser is a research associate in -- I believe 15 she's also in psychopharmacology. 16 Q. Do you know each of these 17 individuals? 18 A. I do. 19 Q. And the subject of her memo to 20 Doctor Pande is Clinical Trials With Psychoactive 21 Medications, is it not? 22 A. Yes, sir. 23 Q. And there's a lot of 24 particular trials listed, are there not? Page 526 1 A. Yes, sir. 2 Q. Are all of those clinical 3 trials listed Prozac clinical trials? 4 A. I don't know that. 5 Q. Can you identify which ones 6 are Prozac clinical trials -- well, it might be 7 easier if you tell me if you see any in here that 8 are not Prozac clinical trials. 9 A. I believe these are all Prozac 10 trials. I cannot identify any that, with this 11 information, could say was not a Prozac trial. 12 Q. The subject of this memo 13 indicates that there's chloral hydrate being 14 given in all of the clinical trials mentioned, 15 Prozac clinical trials mentioned here? 16 A. Correct, that's correct. 17 Q. And chloral hydrate is a 18 hypnotic? 19 A. That's correct. 20 Q. And for the Prozac clinical 21 trials HCAC, do you see that there, the first one 22 listed? 23 A. Yes, sir. 24 Q. Is that a depression clinical Page 527 1 trials? 2 A. That, I don't know, sir. 3 Q. You know it's a Prozac 4 clinical trial? 5 A. I don't know that for sure, I 6 suspect these are all Prozac, so I would have to 7 say that most likely it is. 8 Q. What leads you to suspect that 9 they're all Prozac? 10 A. I'm trying to remember from 11 the codes that precede, I'm trying to think of 12 any other studies I have done. I believe the HC, 13 the first two letters indicate the compound under 14 study. That's to the best of my recollection. 15 Q. And HC indicates Prozac? 16 A. To the best of my 17 recollection, yes. 18 Q. That HCAC study allows 19 Benzodiazepine if a patient complains of 20 agitation, doesn't it? 21 A. Yes. 22 Q. All clinical trials allow 23 chloral hydrate for sleep, do they not? 24 A. That's correct. Page 528 1 Q. Do you know why a clinical 2 trial would allow Benzodiazepine for agitation? 3 A. I don't know that particular 4 clinical trial, but from the code it would appear 5 to be perhaps an early trial, and it may have 6 been more likely that at the time this trial was 7 conducted, that the standard for clinical 8 practice may have allowed for that, and to 9 facilitate enrollment of patients, this would 10 have been permitted. I'm speculating, though. 11 MR. MYERS: Don't speculate. If you 12 have to speculate to answer, don't speculate. 13 A. I really don't know. 14 Q. Does Prozac cause agitation in 15 some patients? 16 A. Agitation has been reported. 17 In my estimation, it may be related to the drug 18 in some of those instances. 19 Q. All right. Of course the 20 chloral hydrate allowed in all of these clinical 21 trials, and Prozac to allow for sleep, isn't it -- 22 or to promote sleep? 23 A. That's correct. 24 Q. That's because in some Page 529 1 patients Prozac causes insomnia, doesn't it? 2 A. That would not be the sole 3 reason as to why one would permit the use of a 4 sleep inducing agent in a patient under such a 5 study. Many patients enter the study with 6 significant insomnia and would require in their 7 participation some use of a sleep inducing agent. 8 Q. That's not what I asked you, 9 is it, Doctor? 10 A. I think that was not the 11 answer to the question. 12 Q. Okay. Why don't you give me 13 the answer to the question. 14 A. Repeat the question? 15 Q. Prozac causes insomnia in some 16 patients, doesn't it? 17 A. In some patients, yes, there 18 is some reports of patients who have difficulty 19 with sleep. 20 Q. Do you know, Doctor 21 Heiligenstein, that people are more prone for 22 violence or aggression if they are deprived of 23 sleep? 24 A. I don't know that answer. Page 530 1 Q. Do you know that individuals 2 are less prone to violence or aggression if they 3 are using hypnotics? 4 A. I don't know that either. 5 Q. Of course, as you can see, the 6 Prozac clinical trials allow the use of 7 hypnotics, do they not? 8 A. They did for a certain -- 9 Q. I didn't mean to cut you off. 10 Apparently Mister Myers has been on a hypnotic 11 and missed that. 12 MR. MYERS: Asleep at the switch. 13 A. In some of these studies it 14 was allowed for just the first two weeks of the 15 study. And quite often, as I recall, in studies 16 that I worked on, it was for a limited time only. 17 Q. Didn't the clinical trials, 18 the United States clinical trials, that you 19 analyzed in your aggression study allow for 20 hypnotics? 21 A. Just looking at this listing, 22 I do not see study HCCD, which is one of those 23 trials that was in the listing that you provided 24 me with earlier. I would have to do a cross Page 531 1 check. 2 Q. Okay. Do it. While you're 3 looking, I thought it was your earlier testimony 4 that you did not include HCCD in the analysis of 5 your paper? 6 A. What I said was I'm not sure 7 that that was a double-blind comparator placebo 8 controlled study, I thought it might be a 9 compassionate use. But what I see -- may I take 10 a look at this and respond to both those 11 questions then, or the first question? 12 (WITNESS REVIEWS DOCUMENT.) 13 A. In reviewing Exhibit 4, it 14 would appear that -- and I think I would like to 15 state that I wasn't sure that that was indeed -- 16 was or was not a double-blind placebo or 17 comparator controlled trial. But in this Exhibit 18 4, an HCCD patient was included in the data 19 analysis, so that would suggest to me that that 20 was indeed a double-blind placebo or comparator 21 controlled trial. 22 Q. And hypnotics were used in 23 that clinical trial. 24 A. Not in that -- Page 532 1 Q. Or allowed in that clinical 2 trial. 3 A. I do not see study HCCD on 4 this particular list. 5 Q. I'm not meaning that that list 6 is a complete listing of all the clinical trials 7 that had ever been conducted. What I want to 8 know is do you know whether or not in the 9 clinical trials that were included in your 10 analysis to support the proposition that 11 Fluoxetine is not associated with increased 12 violence or aggression, do you know that those 13 clinical trials allowed for the use of hypnotics? 14 A. I do not know that with 15 certainty. And given that the trials were over 16 multiple indications, such as obesity and smoking 17 cessation, I'm not sure that because insomnia is 18 not necessarily a component of those illnesses, 19 it would have been necessary to include a 20 hypnotic in those studies. I would have to go 21 back and review individual protocols. 22 Q. But in the depression studies 23 alone, chloral hydrate was included in all of the 24 depression studies? Page 533 1 A. I can't say that because I 2 would have to go through each protocol. And just 3 looking at this list, it appears that some 4 depression studies were not included on this 5 particular list, which would mean then possibly 6 the way Ms. Schlanser prepared this list, it was 7 only those studies that had psychoactive 8 medications, she did not incorporate into the 9 list the studies which may not have used another 10 psychoactive medication or permitted. 11 Q. And she also didn't include, 12 potentially didn't include those clinical studies 13 that had been completed that used psychoactive 14 medications? 15 A. I don't understand that 16 question. 17 Q. Some of the clinical trials 18 that were analyzed by you back in 1990 in this 19 publication were six to eight-week trials, 20 correct? 21 A. That's correct. 22 Q. That are over by the date of 23 Exhibit 8, March, 1993, correct? 24 A. That's correct. Page 534 1 Q. And so you can't use that list 2 to determine -- in Exhibit 8, to determine 3 whether or not the clinical trials analyzed in 4 your study did or did not contain psychoactive 5 medications, can you? 6 A. I think as a first pass, I 7 could make that judgment because this would have 8 included, in my estimation, and this is the first 9 time I've seen this particular communication, 10 that Tina was instructed by Doctor Pande to pull 11 protocols and review those protocols for a 12 possibility -- or for the inclusion, exclusion of 13 the concomitant use of another psychoactive 14 medication. That does not -- by this 15 communication, I cannot tell if she limited that 16 search to depression studies, nor does it say 17 that there were studies in which she did not find 18 the use of concomitant medications, and 19 specifically as that addresses depression 20 studies. 21 Q. Well -- 22 A. I don't know if that makes 23 sense. 24 Q. I don't know that it does, but Page 535 1 I don't know that we're really -- what we're 2 really talking about is of any significance other 3 than the point with respect to your paper, is 4 whether or not the United States clinical trials 5 allowed for administration of hypnotics and other 6 psychoactive medications, correct? That's my 7 point. Do you understand that? 8 A. That that was not addressed in 9 the paper? 10 Q. Right. 11 A. I would have to review the 12 paper, but I assume that's correct. 13 Q. And there is -- from a 14 scientific standpoint, there is a possibility or 15 it would be relevant to know what other 16 psychoactive medications were being used in the 17 U.S. clinical trials in determining whether or 18 not the people in those trials are more likely or 19 less likely to commit a violent or aggressive 20 act? 21 A. I'm thinking for a minute. I 22 would think that it would be appropriate in the 23 endeavor that was undertaken not to cull out and 24 specifically address that because it may be Page 536 1 looked upon as a confounding variable. 2 Q. It's confounding me that you 3 didn't include it and mention it. 4 MR. MYERS: Is that a question? 5 Q. Is that what you mean by a 6 confounding variable? 7 A. No, sir, that's not what I 8 mean by that. 9 Q. U.S. clinical trials excluded 10 patients that were taking neuroleptic 11 medications, did they not? 12 A. I suspect that most did. 13 Q. And neuroleptic medications 14 are more likely to cause individuals to become 15 violent or aggressive, are they not? 16 A. I don't know that that's the 17 case. 18 Q. Well, you don't know that it's 19 not the case either, do you? 20 A. In my experience it's not been 21 the case. 22 Q. Give us an example of a 23 neuroleptic medication that has a calming effect. 24 A. One does not prescribed a Page 537 1 neuroleptic to address a calming effect 2 necessarily. One, when they prescribe a 3 medication, selects targeted symptoms that one 4 hopes to be -- where the treatment would be 5 effective or would be of benefit to the patient. 6 So one would choose targeted symptoms. If an 7 individual -- well, that's really it. 8 Q. What's the most commonly 9 prescribed neuroleptic medication? 10 A. It's a tough call. I would 11 have to say that it might be Thorazine, it might 12 be Mellaril, and it might be -- I don't think 13 it's Haldol. 14 Q. Patients who were taking 15 neuroleptic medications were excluded from the 16 trials, were they not, U.S. clinical trials that 17 were included in your paper? 18 A. Not having reviewed each 19 clinical trial for that specific question, I 20 can't say with certainty, but I would suspect 21 indeed that would be the case, that individuals 22 who required neuroleptic would not be eligible 23 for study. 24 Q. Why? Page 538 1 A. The primary indication for the 2 neuroleptic class of drugs would be primarily 3 psychotic disorders. 4 Q. And aren't individuals with 5 those psychotic disorders more likely to commit 6 violent and aggressive acts than individuals who 7 are suffering from depression? 8 A. I don't have any data that 9 would say definitely yes or definitely no. 10 Q. What is your best clinical 11 judgment? 12 A. My sense is that there may be 13 some increased risk for random violence. 14 Q. In individuals suffering from 15 these disorders that would require a neuroleptic 16 medication? 17 A. Of those individuals who were -- 18 there might be some increase for those 19 individuals who are actively psychotic, yes, sir. 20 Q. And people who were actively 21 psychotic were not included in the U.S. clinical 22 trials, were they? 23 A. I wouldn't think so. 24 Q. In fact were excluded from the Page 539 1 U.S. clinical trials? 2 A. That would be appropriate. 3 MR. SMITH: Let's break for the day. 4 5 * * * * * * * * * * 6 THE DEPOSITION WAS ADJOURNED FOR THE DAY. 7 THE DEPOSITION CONTINUED THE FOLLOWING DAY, 8 APRIL 29, 1994 AS FOLLOWS: 9 * * * * * * * * * * 10 FURTHER EXAMINATION 11 BY MR. SMITH: 12 Q. Doctor, as I understand it, in 13 your capacity as a clinical research physician at 14 Eli Lilly and Company, it was a large part of 15 your duties to review reports of adverse events 16 in connection with the use of Prozac, is that 17 correct? 18 A. Yes, sir. 19 Q. And over the period of time 20 that you were reviewing the adverse events, 21 approximately how many adverse events forms did 22 you review? 23 A. I have no idea. 24 Q. Can you give me numbers in any Page 540 1 amount? 2 A. If I were to estimate, and it 3 may be off considerably, I would say on the order 4 of maybe four or five thousand. 5 Q. And I would assume that those 6 adverse event instances that you reviewed would 7 include all types of adverse events in connection 8 with Prozac? 9 A. Yes, sir. 10 Q. In other words, issues in 11 connection with rash, other medical conditions, 12 headaches, strokes, suicides, overdose, the whole 13 gamut of potentially -- of events that were 14 potentially involved in Prozac, is that right? 15 A. Yes, sir. 16 Q. All of those events would be 17 events that were reported to Lilly by outside 18 sources that were involved with people's use of 19 Prozac, is that right? 20 A. They would have been reported -- 21 not necessarily. Many of those would have been 22 reported by outside sources. If one includes the 23 reports from the sales force as outside, that 24 would be correct as well. A substantial number Page 541 1 of those would be reported by the sales force as 2 they called on physicians. Some of those were 3 reported from internal communications, such as if 4 an employee of Lilly had been taking Prozac and 5 had experienced an event and had mentioned it, 6 that would have been reported as well. 7 Q. Have you ever seen any 8 statistics or numbers concerning the number of 9 Lilly employees who were using Prozac? 10 A. I have not. 11 Q. But you have seen adverse 12 events reported to you where the patient taking 13 the Prozac was a Lilly employee? 14 A. As I recall, yes. 15 Q. I have heard that there have 16 been more adverse events reported with Prozac use 17 than any other medication on the market. Have 18 you heard similar -- figures similar to that? 19 A. I have heard that there have 20 been a large number of adverse events reported, 21 yes, relative to any other compound on the 22 market. The only source where I recall hearing 23 that was in some quotations in the media, that as 24 I recall were provided by CCHR. Page 542 1 Q. You didn't see any internal 2 study by Lilly or anything to refute the 3 allegation that there have been more adverse 4 events reported with Prozac than any other 5 medication, have you? 6 A. I'm not aware of such. 7 (PLAINTIFFS' EXHIBIT NUMBER 9 8 WAS MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Exhibit 9 appears to be a 11 paper authored by you, is that right? 12 A. It's a communication, yes, 13 sir, that I had authored. 14 Q. I don't see a date on this 15 communication. Do you recall when the paper was 16 written? 17 A. I do not recall the specific 18 year. 19 Q. Can you get to maybe one or 20 two years? 21 A. I think I can. 22 Q. All right. 23 A. I suspect I would have 24 authored this in 1988 or 1989. Page 543 1 Q. After Prozac had been on the 2 market for a year or two? 3 A. If it had been authored in 4 1988 and it could have been less than a year. 5 Q. That would mean that this 6 paper was authored before the Teicher article 7 came out. 8 A. If my recollection is correct, 9 that would be the case. 10 Q. What caused you to issue this 11 paper? 12 A. To the best of my 13 recollection, when I returned to Lilly in May of 14 1988, I took and shared -- I took a considerable 15 amount of responsibility for safety monitoring 16 that I shared with my colleagues who were engaged 17 in that activity as well. As there were a number 18 of reports that were being filed, I tried to 19 bring about some organization, some personal 20 organization to my endeavors and wished to 21 emphasize to those with whom I was working of the 22 importance of safety monitoring. 23 Q. And this was before the public 24 controversy concerning -- arose concerning Page 544 1 whether or not Prozac caused suicidality? 2 A. As best I recall, yes. 3 Q. Do you recall at the time that 4 you authored this whether or not you had reviewed 5 any reports of adverse reactions where it was 6 questioned whether or not Prozac caused a 7 particular patient's suicide? 8 MR. MYERS: Let me object to the form 9 only to the extent you used the term adverse 10 reactions as opposed to adverse event. But if 11 you know, answer the question, Doctor. 12 A. Could I have the question 13 repeated, please? 14 (THE COURT REPORTER READ BACK THE 15 PREVIOUS QUESTION.) 16 A. I recall that there were 17 events reported -- to the best of my 18 recollection, there were events reported in that 19 timeframe. 20 Q. The last phrase in the -- what 21 would you call this, a notation or a paper? 22 A. Communication. 23 Q. The last page in the 24 communication says welcome aboard, correct? Page 545 1 A. That's correct. 2 Q. Was this something that was 3 authored for use by new members of the DEN staff 4 or the individuals at Lilly who were responsible 5 for monitoring adverse events in connection with 6 Prozac? 7 A. As best I recollect, this 8 was -- as best I recollect, the audience for this 9 communication would have been new research 10 associates in the DEN unit. 11 Q. Second paragraph says, as the 12 international medical directors heard on their 13 recent visit to Indianapolis, the Drug Evaluation 14 Unit and CNS physicians have been persistent in 15 their follow-up of all serious or potentially 16 serious adverse events. Correct? 17 A. That's correct. 18 Q. There is a handwritten 19 notation between the first and second paragraph 20 that looks like research associates is written in 21 there? 22 A. That's correct. 23 Q. Is that your writing, Doctor? 24 A. Yes, sir. Page 546 1 Q. Where does research associates 2 go? 3 A. That would be referring to 4 those individuals in the Drug Evaluation Unit. 5 Q. So it should maybe read the 6 Drug Evaluation Unit, research associates and CNS 7 physicians? 8 A. Yes, sir. 9 Q. In that same paragraph, in 10 connection with the necessity to follow-up on 11 serious or potentially serious adverse events, 12 you say, quote, this has been necessary as many 13 initial reports provide a bare minimum of 14 information, potentially jeopardizing the drug 15 when the event involves or suggests death, 16 hospitalization, disability, cancer, overdose and 17 congenital anomaly or otherwise perceived as 18 life-threatening and unexpected, paren, our 19 package literature or a greater severity than 20 would otherwise be expected, close paren, period. 21 Correct? 22 A. That's correct, sir. 23 Q. The last sentence of that 24 paragraph says, a one line report has never been Page 547 1 satisfactory even more so since Fluoxetine was 2 marketed. Does it not? 3 A. Yes, sir. 4 Q. Then you go on to say, the 5 following efforts have been undertaken by medical 6 for U.S. domestic reports. Correct? 7 A. Yes, sir. 8 Q. Why was -- and then it lists 9 some items on efforts for U.S. domestic reports, 10 does it not? 11 A. Yes, sir. 12 Q. Were you handling United 13 States reports differently from international 14 reports of adverse events? 15 A. As best as I recollect, the 16 events outside the United States were reported -- 17 were not reported to us as the initial contact 18 quite often, it might have gone to the affiliate 19 in the respective country. Those affilates would 20 prepare a report and they would then communicate 21 that report to us and then that report would be 22 review by us. At that point, if we had 23 additional questions that we thought needed to be 24 asked, we would communicate that back to the Page 548 1 affiliate who had the responsibility for 2 networking with the reporter of the event. 3 Q. Well, were the international 4 reports not treated with respect to these three 5 steps that you mentioned for U.S. domestic 6 reports? 7 A. They would have been treated 8 similarly, to the best of my knowledge. 9 Q. It was just that there was an 10 intervening step before it ever got to you in the 11 United States in that the report would have 12 initially gone to the foreign affiliate, is that 13 what you're telling me? 14 A. Yes, for a physician to review 15 the affiliate. 16 Q. Would a physician with a 17 foreign affiliate have reviewed it prior to it 18 being sent to Lilly in Indianapolis? 19 A. As best I recall, yes. 20 Q. Did that mean there would be 21 less follow up on international reports by Lilly 22 in Indianapolis than there would be for domestic 23 reports in that situation? 24 A. No, not necessarily. Page 549 1 Q. All right. So once a foreign 2 report arrives, it's going to get the same 3 treatment as a domestic report, is that correct? 4 A. To the best of my knowledge, 5 it did, yes. 6 Q. Well, you would be the 7 individual who had as great a knowledge about how 8 these are treated as anyone at Lilly, wouldn't 9 you? 10 A. Yes, sir. 11 Q. You say, first -- going ahead 12 with what you say in your communication. You 13 say, First, all reports are independently 14 reviewed by a physician and a clinical research 15 associate from the DEU, correct? 16 A. That's correct, that's what I 17 state. 18 Q. Is there something -- you 19 paused, is there something incorrect about that 20 sentence with respect to the procedure? 21 A. The research associate outside 22 the United States, as I recall, would not be a -- 23 identified as a research associate in our DEU, 24 they would be a research associate in the Page 550 1 affiliate. So that varies in that sense. 2 Q. But as far as domestic 3 reports, is it accurate what you say concerning 4 what is going to occur first, that being an 5 independent review by a physician and a clinical 6 research associate from the DEU? 7 A. Except in those instances when 8 the report was -- report came to a physician 9 directly and then there may not have been a 10 research associate involved in that particular 11 review. 12 Q. The point is to get a 13 physician at Lilly to review the report. 14 A. Yes, sir. 15 Q. Is that right? 16 A. Yes, sir. 17 Q. What does that physician who 18 reviews that report do in reviewing that report? 19 A. I can speak for myself and how 20 I think others may have handled it. 21 Q. That would be fine. 22 A. As I read the report, and 23 based upon the information available, if the 24 report was a serious report by the criteria Page 551 1 established by the FDA, I would then engage in 2 the algorithm that was necessary. If the report 3 was nonserious and did not appear to be an event 4 of sufficient severity to warrant upgrading, then 5 I would proceed to sign off on that report. 6 Q. All right. So if the report 7 were nonserious, as that term is defined in FDA 8 regulations, you could go ahead and sign off on 9 the report at that time and that information 10 carried thereon would not have to go through the 11 second and third step? 12 A. The second and third step 13 being the algorithm for seriousness in terms of -- 14 Q. No. I'm talking about the 15 second and third step that you mentioned in the 16 remainder of the paragraph, Doctor. 17 A. That's correct, sir. 18 Q. If it's not a serious event, 19 does Lilly not make any association concerning 20 whether or not there is a causal relationship 21 between the drug and the event reported? 22 A. That's correct. 23 Q. If it is a serious event, then 24 Lilly does make an association causally with Page 552 1 respect to whether or not the drug and the event 2 are related? 3 A. Not necessarily. 4 Q. All right. Why would they not 5 if it's not -- if it is a serious event? 6 A. The event must be serious and 7 unexpected for the event to be assigned 8 causality. 9 Q. Okay. Then maybe we better -- 10 A. Did I say serious and 11 unexpected? 12 Q. You said the event must be 13 serious and unexpected before we assign 14 causality. Is that correct? 15 A. That's correct, sir. 16 Q. Define serious. 17 A. Serious is an event that 18 results in hospitalization, as I recall 19 disability, congenital anomaly, death. It could 20 be during part of that time, as I recall, 21 overdose, other reasons serious. 22 Q. Beg your pardon? 23 A. I think there was another 24 category called other reason serious. Page 553 1 MS. ZETTLER: How about 2 life-threatening? 3 THE WITNESS: Life-threatening I think 4 would have been there as well. I'm not sure I 5 captured all of those categories, but those are 6 the ones -- 7 MS. ZETTLER: Cancer and congenital 8 anomaly, do those ring a bell? 9 THE WITNESS: Cancer does, and 10 certainly congenital anomaly. 11 Q. (BY MR. SMITH) Does that 12 complete your definition of serious? 13 A. As best I recall, those would 14 be the -- those would be the defined categories. 15 Q. Define unexpected, as that 16 term is used in making an initial determination 17 concerning whether or not the Lilly physician 18 must assign causality to the event reported. 19 A. The unexpected assignment 20 would apply to those serious events which were 21 not in the package labeling. 22 Q. Why would you not have to 23 assign causality if the event were listed in the 24 package labeling? Page 554 1 A. Those are the guidelines, the 2 regulatory guidelines by which we abide. 3 Q. Do you know if there is any 4 reason for that guideline? 5 A. I don't recall what the reason 6 may be. 7 Q. Do you think that is a 8 reasonable situation, do you think that's a 9 reasonable way to handle this? 10 A. In my estimatimation, it is. 11 Q. Why? 12 A. I suppose I would -- it would 13 be my sense that that information is available to 14 the prescriber and I guess I have confidence that 15 such a decision is something that's been 16 carefully thought through by a regulatory body. 17 Q. Would the reason that you 18 don't assign causality to a serious event that's 19 listed in the package labeling, is because that 20 is an event that is already recognized as being 21 something associated with use of the medication? 22 A. Not necessarily. It would be 23 an event that had occurred in proximity, perhaps 24 while the medication was being administered or Page 555 1 within a period of time of that. 2 Q. And with a certain degree of -- 3 the occurrence within a certain degree of 4 frequency over a number of reports that it would 5 cause it to be listed in the product literature? 6 A. There is a mechanism by which 7 the regulatory body categorizes the occurrence of 8 such events. So there may be infrequent, rare or 9 frequent events. 10 Q. And that depends upon the 11 frequency, does it not, as reported to the 12 regulatory body? 13 A. That assignment reflects 14 events which occurred -- relative to frequency, 15 reflects events which occurred during clinical 16 trials. There is a separate component of the 17 package labeling which includes post-marketing 18 reports which would not have assigned to it a 19 frequency. 20 Q. All right. But after you get 21 into the post-marketing experience, if you start 22 experiencing a particular adverse event with a 23 certain degree of frequency then it may have to 24 be listed in the package literature, correct? Page 556 1 A. That had not been there prior? 2 Q. Yes. 3 A. Yes, sir, that might -- the 4 FDA might very well request that that be included 5 in the post-introduction reports. 6 Q. So the first thing that's 7 going to be done is a determination as to whether 8 or not the event is serious and unexpected, 9 correct? Where you say all reports are 10 individually reviewed by a physician, if it's 11 serious and unexpected, it's going to go to the 12 second level, if it's not serious or unexpected, 13 it's going to be kicked off and become part of 14 another separate body of work that has to be 15 done, correct? 16 A. That would be correct, sir. 17 Q. You say in your memo -- 18 continuing your memo, second, all reports are 19 prioritized for follow-up bases -- for follow-up 20 based on this review, correct? 21 A. That's correct. 22 Q. And is that in effect what 23 you're telling me that there are prioritizing 24 based on the physician's review as to whether or Page 557 1 not it's serious and unexpected, or is there a 2 different category examined in this second step 3 that you mentioned? 4 A. That is a second or different 5 effort. 6 Q. Tell me what that is, Doctor. 7 A. At at the time I returned to 8 Lilly and became engaged in the post-marketing 9 surveillance, to facilitate communication I set 10 up on a regular basis, I believe it was three or 11 four times a week, a meeting with my colleagues, 12 Doctor Beasley and Doctor Wheadon, to discuss 13 adverse events as we were each assigning off on 14 those adverse events, to ensure that we were 15 aware of the serious events that were occurring 16 or might need follow-up. In addition to that, I 17 set up a standing pleading with the DEU research 18 associates, and as I recall that was a meeting 19 that was approximately an hour in duration. And 20 as I recall, initially that meeting occurred as 21 many as five times a week and as we progressed 22 the frequency was reduced to perhaps three times 23 a week. It was in those meetings with my 24 colleagues, Doctor Beasley and Doctor Wheadon, Page 558 1 and then my colleagues in the research associate 2 DEU group, that I would help determine which 3 events we needed more information about and we 4 would assign the task to various individuals in 5 that group of individuals. 6 Q. Was this an operation you 7 personally were directing? 8 A. Yes, sir. 9 Q. You mentioned -- the reason I 10 ask is you mentioned Doctor Beasley and Doctor 11 Wheadon, and I think Doctor Beasley was probably 12 senior to you, at least in terms of service, is 13 that correct? 14 A. That's correct. 15 Q. Did he have a different area 16 that he was supervising or were you over Doctor 17 Beasley in all aspects or -- 18 A. No, not necessarily. It was a 19 very collegial kind of endeavor. 20 Q. I understand that, but 21 somebody had responsibility, ultimate 22 responsibility, correct? 23 A. I'm sorry, ultimate 24 responsibility for? Page 559 1 Q. Accountability. 2 A. I think we were all 3 accountable, and I think that my management would 4 have been accountable because we were 5 accountable. What I would say is that each of us 6 took an active roll and that if there were a 7 cluster of events that required some follow-up, 8 it may very well have been that Doctor Beasley 9 would have been the point person for that 10 particular cluster, and I may have been the point 11 person for another cluster. 12 Q. How were you assigning 13 clusters as that term is used by you? 14 A. That was something that would 15 be decided when Doctors Beasley, Wheadon and 16 myself met in our discussions. 17 Q. Do you recall that you had a 18 particular area of responsibility and Doctor 19 Beasley had another area of responsibility? 20 A. It wasn't a -- necessarily a 21 very defined or clean breakdown. It was an 22 agreement relative to a single event, perhaps 23 relative to several events, that would then be 24 taken, and that was often as more or less on a Page 560 1 volunteer basis or if there was a particular area 2 that someone was looking at, that individual 3 might take that and -- 4 Q. Go ahead. 5 A. In addition, some of those 6 were shared. 7 Q. Okay. I guess the point I'm 8 getting at is, was there a situation where you 9 were taking like suicides and overdoses and 10 Doctor Beasley was taking rashes and GI 11 complaints and Doctor Wheadon was taking 12 coronary, respiratory complaints? 13 A. No, not in that sense. 14 Q. Did anybody have any 15 particular specialty or expertise in any 16 particular area? 17 A. My sense is that we all had 18 equivalent expertise. 19 Q. So some week you might do the 20 investigation on a particular suicide or 21 overdose, the next week Doctor Beasley might do 22 another overdose or suicide, and the same for 23 Doctor Wheadon, correct? 24 A. That's correct. Page 561 1 Q. Or all three of you might be 2 working on separate and independent suicides at 3 the same time, if you happened to have three 4 under investigation? 5 A. That's correct. 6 Q. I'm not assuming that you 7 always had three under investigation, Doctor. 8 A. That would be correct. 9 Q. Or could it be that two of you 10 were working on one particular report, say you 11 and Doctor Beasley were sharing the work on a 12 particular report on a particular suicide? 13 A. I don't recall that being the 14 case. 15 Q. Could it have been a case? 16 A. It would have been unlikely 17 given that we -- it would have been unlikely. 18 It's a possibility. 19 Q. You mentioned to me yesterday 20 the situation with Mister Wesbecker and you told 21 me about a telephone conversation where you, 22 Doctor Leigh Thompson, Doctor Dan Masica and 23 Doctor Zerbe were all talking with this medical 24 examiner investigating this one particular Page 562 1 incident in connection with Mister Wesbecker, 2 correct? 3 A. That's correct. 4 Q. Was it usual to call in a team 5 such as that who are outside the normal reviewing 6 group? 7 A. Yes, it would have been 8 unusual. 9 Q. In other words, Doctor Leigh 10 Thompson was very well at the time of this 11 Wesbecker investigation, either a vice-president 12 or the chief scientific officer of the 13 corporation. I believe you said Doctor Masica 14 was either director or maybe a vice-president of 15 Lilly Research Labs, is that right? 16 A. No, I didn't. What I said was 17 I'm certain that Doctor Thompson was not the 18 chief scientific officer at that time. As best I 19 recall, he was a vice-president of Lilly Research 20 Labs. Doctor Masica would have been a director, 21 not a vice-president. 22 Q. Do you remember any other 23 report of an adverse event where any of these 24 individuals such as this participated in an Page 563 1 investigation? 2 A. Yes, I do. 3 Q. How often would that occur? 4 A. I can't say how often, but I 5 can tell you it happened and they were involved. 6 Q. What would be the occasion for 7 them to be involved? 8 A. Most often it would be in the 9 context of an event which -- 10 MR. MYERS: An event? 11 A. Yes, an event, reported which 12 would have been serious and unexpected where we 13 felt more information was needed. 14 Q. Potential for litigation? 15 A. Oh, no, that was not the 16 driving force. 17 Q. Well, had you had problems 18 then in, you, Doctor Beasley and Doctor Wheadon, 19 in collecting this information? 20 A. Have we had difficulty in 21 collecting information relative to? 22 Q. To an event such that you 23 would need to call in the big gun? 24 A. No. Page 564 1 Q. Or bigger guns, I don't mean 2 to -- 3 A. Repeat the question so I make 4 sure I understand. 5 Q. You said that this 6 investigation such as that occurred with Mister 7 Wesbecker's tragedy was a situation where some of 8 the leaders, I think that's an apt 9 characterization, don't you? 10 A. Yes, sir. 11 Q. Some of the leaders within the 12 Prozac group were called in and actively 13 participated in an investigation, correct? 14 A. Yes. 15 Q. All right. But the ordinary 16 situation was a situation where you, Doctor 17 Beasley and Doctor Wheadon would handle these 18 matters, correct? 19 A. That's correct. 20 Q. Was there something more, what 21 triggered -- what would trigger getting in the 22 bigger guns on a particular investigation? 23 A. It would be that an event had 24 occurred of sufficient severity or specificity Page 565 1 outside the information contained in the package 2 label such that we felt package labeling changes 3 would be necessary. 4 Q. So a package labeling change 5 might be necessary as a result of a particular 6 event reported, then it's likely that you're 7 going to call in individuals such as Doctors 8 Thompson, Masica and Zerbe? 9 A. They were so much a part -- 10 they were in physical proximity to us and so much 11 a part of the developmental process with Prozac 12 that that would be a natural occurrence. 13 Q. But they weren't normally part 14 of the process of reviewing this massive amount 15 of adverse events that were coming in? 16 A. Yes, they were. 17 Q. I thought normally, as set out 18 by this memo, you, Beasley and Wheadon did it? 19 A. We did it in terms of the 20 signing off on the 1639 forms. We did have 21 quarterly extensive reviews to our senior 22 management that -- in which those individuals 23 would have been kept abreast of events occurring 24 with Fluoxetine. Page 566 1 Q. When you say quarterly, that 2 tells me once every three months. 3 A. Yes, sir. 4 Q. Four times a year? 5 A. Yes, sir. 6 Q. They were called in four times 7 a year regularly and you were doing this five 8 days a week, fifty weeks a year, regularly? 9 A. Yes, sir. 10 Q. I gave you two weeks vacation, 11 all right, is that correct? 12 A. That's correct. 13 Q. This other murder that 14 occurred, were Doctor Thompson, Doctor Masica and 15 Doctor Zerbe involved in the investigation of 16 that? 17 MR. MYERS: I object to the form. Has 18 he identified another murder? 19 MS. ZETTLER: The one he was talking 20 about yesterday that he recalled from a line 21 listing. 22 MR. OLTMANS: I don't believe it was a 23 murder. 24 MS. ZETTLER: There was another murder Page 567 1 that you were talking yesterday. 2 MR. MYERS: I don't think so. I just 3 don't think you recall. Maybe there was another 4 event, he talked about some other events, but I 5 think you're wrong. 6 MS. ZETTER: Wasn't there another 7 occurrence where a woman killed her husband or 8 killed somebody else? 9 THE WITNESS: I don't believe we 10 discussed that yesterday. 11 MS. ZETTLER: Wasn't there another 12 event such as that around the same period of time 13 in '88 such as Wesbecker? 14 THE WITNESS: Is that -- you're asking 15 me a question? 16 MR. SMITH: This is separate, we don't 17 need your help, Larry. 18 THE WITNESS: Do you want me to 19 respond to that? 20 MS. ZETTLER: Yes. 21 THE WITNESS: At the time of the 22 Wesbecker tragedy, as I recall, there was a media 23 account of a woman in Wisconsin who had murdered 24 a friend. Page 568 1 MS. ZETTLER: Okay. 2 Q. (BY MR. SMITH) And had they 3 been involved, that is they being Leigh Thompson, 4 Dan Masica, and Doctor Zerbe, in that 5 investigation? 6 A. In terms of being kept abreast 7 of information that was available, yes. 8 Q. But in terms of actually being 9 on the phone and talking to a coroner or a 10 reporting physician or anything of that nature, 11 were they involved in that instance to that 12 extent? 13 A. Not that I recall. 14 Q. Let's go back to your memo or 15 your communication. You say third, a trigger 16 mechanism is in place for immediate follow-ups of 17 all reports of death or other serious unexpected 18 events. Correct? 19 A. That's correct. 20 Q. What was the trigger mechanism 21 in place for immediate follow-up? 22 A. When that was brought -- when 23 that information was brought to an individual 24 physician for review, that physician could and Page 569 1 would assign responsibility to a research 2 associate to follow up that event or the 3 physician may very well have followed that up in 4 and of himself. 5 Q. What was the trigger 6 mechanism? 7 A. The trigger mechanism, I 8 suppose that's a terminology more than a specific 9 event, what I'm saying there I think is sort of 10 repeating myself and saying a serious unexpected 11 event would have been a mechanism that would 12 result in efforts to follow up the event. 13 Q. So there isn't really a 14 separate trigger mechanism? 15 A. As best I recall, the separate 16 trigger mechanism was a serious unexpected event 17 which then led to have caused the follow-up. 18 Q. That's my question, what 19 follow-up? 20 A. Let me just try and capture 21 this because some of it comes back as we talk. 22 The trigger mechanism, I will -- as best I 23 recollect, trigger mechanism was the serious 24 unexpected with a decision that this event Page 570 1 required immediate follow-up. And I can't say 2 that would have been true for every such event, 3 but I think that was true in most events that 4 occurred in such fashion. And -- I apologize, I 5 need to have the question repeated because I was 6 trying to think through this as that question was 7 being asked. 8 Q. What was the follow-up? 9 A. Thank you. I can tell you 10 that in my situation I would initiate many calls 11 to the reporter of the event or a research 12 associate would have done likewise, but we would 13 have not have -- we would have attempted not to 14 duplicate one another's events with a single 15 report. 16 Q. What else? 17 A. Based upon our ability to 18 reach the reporter, based upon the reporter's 19 willingness to provide information, if the 20 information that was obtained was sufficient, 21 that would have sufficed for the further 22 follow-up of that particular report. 23 Q. Say that again. 24 A. That would have sufficed for Page 571 1 the follow-up of that particular report. 2 However, there would have been instances and 3 there were instances where we requested 4 laboratory information, clinical information, 5 results of postmortem examinations and even on 6 some occasions one may have flown to a particular 7 site to obtain more information. 8 Q. Did you ever do that? 9 A. I did. 10 Q. Did you ever do that in 11 connection with a suicide? 12 A. I did not. 13 Q. Did you ever do that in 14 connection with an overdose? 15 A. Did not. 16 Q. Did you ever do it in 17 connection with an event that would generally be 18 characterized as violent or aggressive behavior? 19 A. I do not recall that I did. 20 No, I did not. 21 Q. Do you know of anybody at 22 Lilly that ever did do that, fly to a particular 23 sight to investigate an overdose or a suicide, 24 and when I say suicide I mean suicide attempt, Page 572 1 also, or suicidal ideation or a claim of 2 aggressive violent behavior? 3 A. As best I recall, I believe 4 Doctor Wheadon flew to Boston to meet with 5 Doctors Teicher and Cole relative to the report 6 that they had published. 7 Q. Those were suicide ideation 8 reports? 9 A. Yes, sir. I have a 10 recollection that a research associate may have 11 flown to a sight to obtain information regarding 12 of the death of a patient suspected of a drug 13 interaction with monoamine oxydase inhibitor and 14 Fluoxetine where there was some question as to 15 whether the woman had overdosed. 16 Q. Was that a case you were 17 investigating? 18 A. I was involved with that, yes, 19 sir. 20 Q. Do you recall the location? 21 A. As best I -- I'm sorry. 22 Q. Where the clinical research 23 assistant went? 24 A. As best I recall, it was the Page 573 1 state of Florida, but I don't recall the city. 2 Q. Any others? 3 A. I don't recall others. That 4 doesn't mean they don't exist, but I just don't 5 recall them. 6 Q. What other follow-up would be 7 done? 8 A. There may have been contact 9 with consultants who had seen a patient apart 10 from the primary reporter. There may have been -- 11 I mean in terms of, this would be a possibility 12 and in some instances it did occur, that one 13 would have direct contact with the medical 14 examiner. I do recall that I initiated phone 15 contact with a family member of an individual 16 that had been reported in an event. 17 Q. What kind of event? 18 A. It was a suicide-homicide. 19 Q. Where did that event occur? 20 A. Madison, Wisconsin. 21 Q. Go ahead. You were listing 22 follow-up. 23 A. Other efforts. As I recall, 24 with some events to better understand the event Page 574 1 that was reported, we might have collected some 2 tissue, bodily tissue from an individual in which 3 an event had been reported. Very early we 4 offered in our follow-up to reporters of adverse 5 events that we could provide analysis of blood 6 levels of Fluoxetine and its metabolite, given 7 the difficulty with which it took to do that test 8 and the uncertainty about the accuracy of the 9 clinical labs outside of the one that we used. 10 Q. Are you saying that you all 11 only -- you all were the only ones that had a lab 12 with the sophistication and with the personnel 13 trained to determine Fluoxetine levels and the 14 levels of its metabolite in blood? 15 A. Very early, as I understand 16 it, and I'm not an expert in laboratory medicine, 17 the procedure was very complicated. And until 18 labs could be standardized, which is the process 19 that labs go through to run -- to do such 20 testing, whatever the test may be, it could be -- 21 labs periodically must be standardized for even 22 routine tests. But when there is a new compound, 23 labs routinely are standardized to validate their 24 ascertainment of levels. Page 575 1 Q. Was your laboratory facility 2 here on premises at Eli Lilly and Company? 3 A. It was not. We had one such 4 lab here but that's not the one that we used. 5 Q. Who did you use? 6 A. We used a lab, Wisconsin 7 Analytical Research Laboratories, I believe is 8 what it's called. 9 Q. Did you go over there and 10 train those people how to find the Fluoxetine? 11 A. I believe they were trained, 12 they had to be, you know, the labs had to be 13 standardized. 14 Q. Anything else? 15 A. There may have been other 16 things, but I don't recall those efforts. 17 Q. You go on about the middle of 18 your communication and you say, quote, on 19 occasion it has been necessary for physician 20 and/or CRA's to personally visit a reporter to 21 gather information including medical records. It 22 is not unusual for multiple phone calls, number 23 greater than fifteen, to be made to as many as 24 five leads to establish the validity of a report Page 576 1 and to follow-up accordingly. Correct? 2 A. That's correct. 3 Q. Then you go on to say, the 4 vast majority of the time, the follow-up has been 5 favorable, that is, an event has become a 6 non-event. Correct? 7 A. That's correct. 8 Q. So has the -- it reads to me, 9 Doctor, like the purpose of this investigation is 10 in order for that investigation to be favorable, 11 the event has to become a non-event. Is that 12 what you mean to say here? 13 A. No, sir. 14 Q. Why did you say it that way 15 then? 16 A. What I'm trying to communicate -- 17 what I tried to communicate I believe in this 18 communication, is that the additional information 19 that was oftentimes obtained with this level and 20 effort of follow-up really allowed one to more 21 correctly assess severity and/or relatedness and 22 that frequently that information was indeed 23 favorable, meaning that information was very 24 helpful and it did not appear that such events in Page 577 1 the majority of those instances were related to 2 the use of Fluoxetine. 3 Q. Well you say the follow-up has 4 been favorable, and you go on to say, I'm quoting 5 you exactly, you say that is an event becomes a 6 non-event, correct? 7 A. That's correct. 8 Q. Obviously the words say what 9 they say, but the import of the meaning to me is 10 is that a favorable follow-up is a follow-up 11 which results in an event becoming a non-event as 12 far as you're concerned. 13 MR. MYERS: I object to the form. Go 14 ahead and answer the question. 15 A. That was not the intent of 16 that communication. 17 Q. You know, I really wonder 18 about it because you go on to say, you say e.g. 19 there, which means for instance, isn't that what 20 e.g. means to you? 21 A. Yes, sir. 22 Q. Or that is. A reported death 23 was not true, correct? You say that, don't you? 24 A. Yes, sir. Page 578 1 Q. Somebody that was reported 2 dead was not, was really alive? 3 A. That's correct. 4 Q. Then you go on to say, you 5 give another example, or the severity of the 6 event is lessened, correct? 7 A. That's correct. 8 Q. Then you say -- you give some 9 more examples, you say e.g. leukemia in a patient 10 who was malingering, correct? 11 A. Yes, sir. 12 Q. Is that the term you used? 13 A. Yes, sir. 14 Q. Define malingering for us, 15 Doctor. 16 A. The patient was lying. 17 Q. Okay. Are you telling me that 18 leukemia -- that you found instances where people 19 suffering from the many times fatal illness of 20 Leukemia were lying? 21 A. I remember this instance, and 22 in this particular instance, the patient reported 23 that he had leukemia, but he was lying to the 24 physician. The physician reported it to us and Page 579 1 we initiated our investigation and it turned out 2 that the patient had never had nor was currently 3 suffering from leukemia. 4 Q. Okay. Then you give another 5 event, aplastic anemia in a patient with 6 myelofibrosis. What's aplastic anemia? 7 A. Aplastic anemia is a condition 8 in which one ceases to make red blood cells. 9 Q. Okay. What's myelofibrosis? 10 A. Myelofibrosis is a disorder of 11 one's bone marrow in which the tissue becomes 12 fibrotic and which results in the cessation quite 13 often of the manufacture of red blood cells. 14 Q. Is it more or less severe than 15 aplastic anemia, or do you know? 16 A. Well, I think that one can 17 progress to the other, so myelofibrosis might be 18 seen as somewhat less severe although the 19 ultimate outcome may be progression to a full 20 aplastic anemia. 21 Q. Then you go on to say, a 22 stroke in a patient with a multiple personality 23 disorder in which one personality presented with 24 stroke symptoms, correct? Page 580 1 A. That's correct. 2 Q. So you pointed to instances 3 where people really didn't have anything wrong 4 with them or what they thought was wrong with 5 them didn't prove to be the case, correct? 6 A. Not always. That was the case 7 in some instances. There were other instances in 8 which there were more logical medical 9 explanations for the event as it occurred. So it 10 did not become a non-event, but rather an event 11 related to another condition. 12 Q. To another condition? 13 A. Condition. 14 Q. So it's favorable when you 15 don't tie causality to Prozac? 16 MR. MYERS: Let me object to the form 17 of the question. I don't think that's what the 18 memo says and I don't think that's what he said. 19 But go ahead and answer it, Doctor. 20 A. I don't think that's what I 21 was saying. I think what I was trying to say is 22 that the information that we were able to obtain 23 through the sources, it was helpful. And to use 24 that as an example and perhaps as a motivator Page 581 1 that people should be on top of those things, 2 that quite often the information would be helpful 3 in dispelling notions of relatedness or 4 causality. 5 Q. What percentage of these 6 adverse event reports that were serious and 7 unexpected did you find were really not events at 8 all? You give me four examples here which you 9 characterize as favorable, correct? 10 MR. MYERS: Well, let me object to the 11 form. You've asked him two things now, there 12 were two questions in that. 13 A. Could you repeat the question? 14 Q. What percentage of the serious 15 unexpected adverse events did you find were not 16 events at all? 17 A. I have no idea. 18 Q. Well, you give four examples 19 here, don't you? 20 A. Yes, sir. 21 Q. Was it -- of those serious 22 unexpected events, did you find that there were 23 fifty percent that were not really events at all? 24 A. I don't know, but it would not Page 582 1 have been fifty percent. 2 Q. Twenty-five percent? 3 A. I doubt it. 4 Q. Ten percent? 5 A. I don't know. 6 Q. Somewhere between ten and 7 twenty-five percent? 8 A. I just don't know. 9 Q. But your wording here does 10 indicate that a follow-up is favorable if an 11 event becomes a non-event, doesn't it? 12 A. I think that would be a 13 literal interpretation of that. I don't think 14 that's what I intended to communicate 15 necessarily. 16 Q. But if you read it for what it 17 says, that's a literal interpretation of what it 18 says, isn't it, Doctor? 19 A. I would say that's your 20 literal interpretation. I don't know how 21 somebody else would read that. 22 Q. Do you frequently write 23 communications such as this where what you mean 24 can be subject to a variety of interpretations? Page 583 1 A. That's possible. 2 Q. The last paragraph says, 3 without question there have been occasions when a 4 physician-reporter would only speak with a 5 physician monitor. All Lilly physicians should 6 be prepared and willing to take the initiative to 7 follow up serious unexpected reports. Then you 8 go on to say, such intense post-marketing 9 surveillance insures the safety of patients 10 treated with Fluoxetine and provides us with more 11 meaningful information as we function in our role 12 as information providers and protects our drug 13 ensuring its longevity. Correct? 14 A. Correct. 15 Q. Could one literally interpret 16 this paragraph to mean, Doctor, that your 17 post-marketing surveillance could be calculated 18 to protect the drug and ensure its longevity? 19 A. That would not be my 20 interpretation. 21 Q. That's what you wrote though, 22 wasn't it? 23 A. No, that's not what I wrote. 24 Q. Did you not write the word, Page 584 1 and protects our drug, comma, ensuring its 2 longevity? 3 A. I did indeed write that. 4 Q. And you wrote those words in 5 connection with steps in the post-marketing 6 surveillance process, did you not? 7 A. That's correct. 8 MR. SMITH: Lets take a break. 9 (A SHORT RECESS WAS TAKEN.) 10 Q. (BY MR. SMITH) Doctor, do you 11 know whether or not there was an investigation -- 12 whether you did any investigation into any of the 13 suicides that occurred in the State of Texas? 14 A. I don't recall. 15 Q. Do you recall whether you 16 investigated a suicide involving a gentleman by 17 the name of Biffle, Michael Biffle? 18 A. I don't recognize that name. 19 Q. Do you recall investigating a 20 suicide involving a gentleman by the name of Carl 21 Welch? 22 A. I don't recognize that name. 23 Q. Do you recall investigating a 24 suicide in Dallas involving a lady by the name of Page 585 1 Kung, K-U-N-G? 2 A. I do not recall. 3 Q. Do you recall investigating a 4 suicide in Beaumont, Texas, involving a young 5 woman by the name of Reves, Christine Reves? 6 A. I don't recall that. 7 Q. Do you recall investigating 8 any suicides in the State of Texas? 9 A. I have a vague recollection, 10 but it's -- I did not -- I'm not sure I would 11 have logged into my memory the state in which an 12 event might have occurred. 13 Q. What would you log into your 14 memory? 15 A. Most likely it would be the 16 contact and information. 17 Q. The name of the physician who 18 reported it or the entity that reported it? 19 A. Yes, sir. 20 Q. Do you recall an attempted 21 suicide -- wait a second. Do you recall an 22 attempted suicide by a fellow by the name of Don 23 Mcleod, M-C-L-E-O-D? 24 A. I don't recall. Page 586 1 Q. An individual who attempted 2 suicide by carbon monoxide poisoning and was 3 later found and survived but suffered extensive 4 brain damage -- later found and revived but 5 suffered extensive brain damage. 6 A. I don't recall. 7 Q. Do you recall investigating 8 this Reves suicide where the young lady laid down 9 on some train tracks and allowed a freight train 10 to run over her head? 11 A. I don't remember that 12 incident. 13 Q. Do you recall investigating 14 the suicide of John Di Silvestro in Chicago 15 Illinois? 16 A. I don't recall that name. 17 Q. A young man who jumped in 18 front of a Chicago Transit Authority train. 19 A. I do not recall that. 20 Q. Do you remember investigating 21 the suicide of one Shane Gardner in Champagne, 22 Illinois? 23 A. I don't recall that. 24 Q. A young man who committed Page 587 1 suicide by carbon monoxide poisoning. 2 A. I do not recall. 3 Q. Do you recall investigating 4 any suicides that you're aware of that have 5 resulted in litigation, other than the Wesbecker 6 matter? 7 A. Resulting in litigation? 8 Q. Or where there was a claim 9 made that Lilly should respond in damages as a 10 result of the death of or injuries to the 11 individual taking Prozac? 12 A. I have a vague recollection of 13 seeking additional information about, as I 14 recall, an adolescent who had committed suicide. 15 And I don't recall with certainty that there was 16 litigation pending, but I seem to recollect that 17 at some point after that there was litigation. 18 Q. Where was that death? 19 A. I don't recall, sir. 20 Q. Do you remember any other 21 identifying data about that? 22 A. I have a vague recollection 23 that he was sixteen years of age. 24 Q. Do you remember the mode of Page 588 1 death? 2 A. I do not. 3 Q. Do you remember what you did 4 in connection with that matter? 5 A. As I best recollect, I tried 6 to or did in fact contact the reporter of the 7 event. 8 Q. Was the reporter a physician 9 or a Lilly or Dista sales representative? 10 A. It would have been a 11 physician. 12 Q. Do you remember where that 13 physician was located? 14 A. No, sir. 15 Q. Do you remember what 16 information you learned from that physician? 17 A. I do not. 18 Q. Approximately how many 19 suicides have you investigated in your capacity 20 as a clinical research physician for Eli Lilly 21 and Company? 22 A. I don't know. 23 Q. I know you may not have an 24 exact number, I want an estimate of the number of Page 589 1 suicides. 2 A. The question is completed 3 suicides? 4 Q. For now. I'm going to go 5 through attempted suicides and suicidal ideation, 6 but if you're having a great deal of difficulty 7 and you could answer me in that block of 8 suicides, attempted suicides and suicidal 9 ideation, I'll take it that way too, if that 10 would help you. 11 MR. MYERS: Doctor, let me tell you 12 that if you can give Mister Smith a reasonable 13 estimate, then by all means do that, but if you 14 have to guess or speculate, don't do that. But 15 if you can give him a reasonable estimate, do 16 that. 17 A. I don't think I can give you a 18 reasonable estimate, I don't think I can. 19 Q. How many 1639s or reports in 20 any manner has the Eli Lilly and Company received 21 concerning suicides, attempted suicides, suicidal 22 ideation? 23 A. How many have we received? 24 Q. Uh-huh. Page 590 1 A. I'm unaware of the total 2 number. 3 Q. Do you know of anybody that's 4 ever counted them? 5 A. Well, we have certainly kept 6 track for some time regarding any death that may 7 have occurred when an individual was taking or 8 had been taking Fluoxetine, whatever the means of 9 death, whatever the cause. I suspect at some 10 time there were some counts of those presented in 11 various meetings, but I do not recall the 12 specifics. 13 Q. It numbers in excess of a 14 thousand, doesn't it? 15 A. I don't know that. 16 Q. It numbers in excess of two 17 thousand, doesn't it? 18 A. I don't know that either. 19 Q. You wouldn't deny that either, 20 would you? 21 A. No, sir. 22 Q. Have you ever found in your 23 investigation, Doctor, that a suicide or 24 attempted suicide was causally related to the use Page 591 1 of Prozac? 2 A. I do not recall in my 3 estimation that I thought a suicide or suicide 4 attempt was causally related to Fluoxetine. 5 Q. You never signed off on a 1639 6 or any type of report that, yes, the suicide or 7 attempted suicide was causally related to the use 8 of Prozac? 9 A. Yes, I may have signed off 10 that it possibly might be related. 11 Q. There's a term there, isn't 12 it, on a 1639 or a term that you have to use? 13 A. There is some language, I'm 14 trying to recall if that language relative to 15 causality changed at any point in time, I have a 16 vague recollection that it did, but there is some 17 language there. 18 Q. What is that language? 19 A. As I recall something to the 20 effect is there any reasonable possibility that 21 this event may be related to the drug or 22 something like that. 23 Q. Are you sure that's the 24 language? Page 592 1 A. No, I'm not sure. 2 Q. Your recollection is that 3 there is a reasonably -- the question is is there 4 a reasonable possibility that the event is 5 related to the drug? 6 A. That's the best of my 7 recollection, yes. 8 Q. Could the language be that the 9 question is whether or not it's reasonably 10 related to the use of the drug? 11 A. That could have been the 12 language. 13 Q. Does that sound familiar to 14 you? 15 A. At some point in time. 16 Q. Huh? 17 A. At some point in time that 18 could have been the language and that sounds 19 familiar, but a sharper recollection is there a 20 reasonable possibility, but I would have to see 21 those reports. 22 Q. What does a reasonable 23 possibility mean to you? 24 MR. MYERS: Before he answers, let me Page 593 1 object to the form to the extent that the 2 terminology you're questioning about is a 3 regulatory term that's defined by law. But tell 4 him what it means to you. 5 A. I could tell you the way we 6 were instructed to interpret that and that is if 7 there's any possibility whatsoever, even the 8 slightest possibility, then one would be 9 conservative and assign yes. 10 Q. Isn't the word that you used 11 in both of these characterizations is reasonable 12 or reasonably? 13 A. Yes, sir. 14 Q. Doesn't that connote to you 15 that the relationship must be reasonable between 16 the use of the drug and the event described? 17 MR. MYERS: Let me object to the form 18 of the question in that it's a 19 mischaracterization of his entire testimony. Go 20 ahead and answer, Doctor. 21 A. What I can tell you is how I 22 interpreted that, and I interpreted that 23 according to the guidelines that we used at Lilly 24 during those times, and that was if there is the Page 594 1 remotest, slightest possibility, then one should 2 be conservative and assign yes. 3 Q. Where is that written that 4 that guideline should be applied? 5 A. I don't know that it is 6 written, it was an oral communication. 7 Q. From who to who? 8 A. From various components of the 9 organization to physicians who were responsible 10 for reviewing events that occurred during 11 post-marketing surveillance. 12 Q. Give me the names of the 13 components and the individuals you are talking 14 about. 15 A. Regulatory, Doctor Max 16 Talbott, as I recall, legal -- 17 Q. Who? 18 A. I believe that was, you know, 19 I think it would have been a collective sense, 20 but the name that would come to mind would be 21 Mary Huff. Medical, everyone in medical, but 22 certainly from the top Doctor Leigh Thompson, 23 Doctor Zerbe. 24 Q. So it's your testimony that Page 595 1 it's Lilly's position that there should be a 2 causal relationship acknowledged if there is any 3 possibility, even the slightest, that there may 4 be some relationship between the drug and the 5 event? 6 MR. MYERS: I object to the form. Go 7 ahead and answer it, Doctor. 8 A. Would you please repeat the 9 question? 10 (QUESTION READ.) 11 A. I would say that it's the 12 position of those components of the organization 13 that I just mentioned, that I recall legal, 14 medical and regulatory, that we should be as 15 conservative as possible when assigning 16 causality, looking for the most remote situation 17 where a reporter or an internal individual has a 18 question as to whether there is any possible 19 relationship. 20 Q. So if there's any possibility 21 that there is a relationship, then legal, medical 22 and regulatory at Lilly are going to make a 23 determination that there is a relationship 24 between the use of the drug and the event Page 596 1 reported? 2 MR. MYERS: Hold on, let me object to 3 the form of the question. You mischaracterized 4 what he said as to who would make that decision. 5 Go ahead and answer it, Doctor. 6 A. What I would say is the 7 communication from those components to the 8 physician who had responsibility for reviewing 9 those reports was that it was something that was 10 in the hands of the physician reviewing each of 11 those reports. 12 Q. That the physician should 13 assign a reasonable relationship between the use 14 of the drug and the event under investigation if 15 those situations exist? 16 MR. MYERS: I object to the form. Go 17 ahead and answer. 18 A. Well, the physician in most 19 instances must assign causality for serious and 20 unexpected reports, but not all. 21 Q. I don't understand that 22 answer. 23 A. If an event was an event with 24 litigation pending, regulatory requirements do Page 597 1 not require that we assign causality. 2 Q. I'm not worried about 3 litigation pending, I'm worried about what you're 4 doing as a clinical research physician in 5 reporting whether or not you, in your 6 investigation, believe that there is a causal 7 relationship between the use of the drug and the 8 event complained of. 9 A. Are you asking me what I 10 believe in terms of the validity that has been 11 alleged about the relationship? 12 Q. Well, I would assume that 13 you're not going to check that there is a causal 14 relationship or that the use of the drug was 15 reasonably related to the adverse event unless 16 you have a belief that it indeed was? 17 MR. MYERS: I object to the form. 18 A. No, that's not the case. 19 Q. So you lie when you say yes, 20 causally related, on a particular adverse event 21 report that says that the use the of the drug was 22 reasonably related to the adverse event? 23 MR. MYERS: Hold on. Let me object to 24 the form and ask you politely, Paul, don't start Page 598 1 to argue with him or become accusatory with him. 2 Go ahead and answer the question to the extent it 3 was a question. 4 A. No, I did not lie. 5 Q. Are you applying meaning, 6 other than English, to the form where it asks was 7 the use of the drug reasonably related to the 8 event complained of? 9 MR. MYERS: I object to the form. 10 A. I would like to clarify. If 11 an event was reported to us and it was reported 12 to us as serious and unexpected, so it would meet 13 those criteria, and if that reporter, as a 14 physician, related that he or she felt that the 15 event may have been related, in spite of the fact 16 that I -- with the information I have available 17 in my assessment there was not a causal 18 relationship, then I would take the conservative 19 approach and abide by the reporting physician's 20 assessment. 21 Q. Okay. Now are you telling me 22 that it's the reporting physician's assessment 23 that is the key here? 24 A. No. In some instances, I may Page 599 1 disagree with the reporting physician, but I have 2 not had the benefit of seeing that patient and I 3 don't know -- and this was more or less agreed 4 upon that when such a physician would make such a 5 report, that pending additional information, we 6 would assign yes to that causality based upon a 7 physician's report. 8 Q. I thought you were going to 9 make a three step investigation of these reports, 10 weren't you? 11 A. The plan -- 12 Q. Can that question not be 13 answered yes or no? 14 MR. MYERS: Hold on. Doctor, you can 15 answer it yes or no if you can, but if you need 16 to explain, explain. If you can answer it yes or 17 no, do that. 18 A. Could you repeat the question? 19 Q. I thought you were going to 20 make a three step investigation into these 21 reports that were serious and unexpected as per 22 Exhibit 9, your own communication to your other 23 colleagues in the post-marketing surveillance 24 department? Page 600 1 A. That's correct. We attempted 2 to follow up on every serious unexpected report. 3 Q. According to Exhibit 9, if 4 what you say is true, you're going to make -- 5 it's not unusual for multiple phone calls, number 6 greater than fifteen, to be made, correct? 7 A. That's correct. 8 Q. And as many as five leads to 9 establish the validity of the report, won't you? 10 A. That's correct. 11 Q. All right. So it appears to 12 me that from reading Exhibit 9, there's going to 13 be great care exercised by you people there to 14 determine the validity of the report. 15 A. There was. 16 Q. And is? 17 A. And is, as far as I know. 18 Q. So I wouldn't think that 19 you're leaving it up to the reporter to make the 20 determination as to whether or not there is a 21 causal relationship between the use of the drug 22 and the event complained of, correct? 23 MR. MYERS: I object to the form, you 24 mischaracterized what he said. Go ahead, Doctor. Page 601 1 A. It is highly likely that 2 reporters in those instances were contacted and 3 where possible additional information was given. 4 I do recall occasions when reporters did not want 5 to provide additional information and where those 6 instances were the case, when a physician 7 relative to the serious unexpected report 8 restated his or her position, without the 9 parallel information that we could obtain for a 10 medical event that would have laboratory -- a 11 laboratory basis and information relative to it, 12 with the reporter and event such as suicide, a 13 completed suicide, we could go no further. 14 Q. What do you mean, go no 15 further? 16 A. We could contact the reporter 17 and ask for information -- as much information as 18 possible. 19 Q. So you're saying that if it 20 comes to a stalemate, that is you can't prove or 21 disprove or make the report more clear, that 22 you're going to accept the judgment of the 23 reporter? 24 MR. MYERS: Let me object to the form. Page 602 1 Stalemate is your word, not his. 2 MR. SMITH: Exactly. 3 A. Where the reporter, and this 4 is in this timeframe, sir, that I'm speaking of 5 because we're addressing this particular memo 6 which I stated to the best of my recollection 7 would have been a communication in 1988 or '89, I 8 would have, in taking the report if I were the 9 receiver of the report and/or called the 10 physician or if I had followed up, I would have 11 asked for additional information. If that 12 individual had ascribed causality, I would not 13 have made -- I might have challenged, but I would 14 not have changed that physician's assessment, at 15 which point I took the very conservative approach 16 and would abide by that physician's assessment 17 although I might disagree. 18 Q. But as far as reporting it to 19 the regulatory authorities, you're going to use 20 the physician's assessment? 21 A. Pardon? 22 Q. As far as reporting it to the 23 authorities, you're going to use the physician's 24 assessment? Page 603 1 A. I took the very conservative 2 approach and used his or her assessment. 3 Q. Whether it's conservative or 4 liberal, can't my question be answered yes or no? 5 MR. MYERS: If it can, Doctor, do so, 6 but if it can't, you don't have to answer yes or 7 no. 8 A. I feel that I need to qualify 9 that when I give you that answer for it to 10 reflect an accurate answer, so therefore I would 11 say in this particular instance when individuals 12 were reported to have committed a suicide and 13 that suicide committed a serious unexpected 14 report, which it would have, and where that 15 individual reporter would have said I think there 16 may be a relationship here, however slight or 17 however great, in spite of the fact that I might 18 not have agreed, I would have said -- I would 19 have signed off to the best of my recollection 20 that that was related. 21 Q. All right. And of course 22 because your personal opinion, Doctor, is that 23 you don't think a suicide is ever related to 24 Prozac, do you? Page 604 1 A. In my best estimation, it is 2 not. 3 Q. You held that opinion when you 4 began working for Lilly, didn't you? 5 A. Well, I had not had any 6 experience whatsoever with Fluoxetine prior to 7 coming to Lilly. 8 Q. Well, you prescribed it before 9 you came to Lilly. 10 A. No, I did not. 11 Q. Oh, you mean you went to 12 Lilly, went back into private practice for a 13 short time and came back to Lilly. Okay, by the 14 time you came back to Lilly, you were of the 15 opinion that Prozac didn't cause suicidality? 16 A. I'm not sure that I would 17 really have thought to question that. My 18 experience with other antidepressants when in the 19 course of treatment patients became suicidal, I 20 did not ascribe that suicidality to the 21 medication being used. 22 Q. I'm not talking about other 23 antidepressants. Is Prozac just like any other 24 antidepressant, Doctor? Page 605 1 A. It's similar to some others 2 that are available, but not the same. 3 Q. Don't you believe it's got 4 some specific benefits that warrant it being on 5 the market? 6 A. Yes, sir. 7 Q. Okay. I'm not talking about 8 other antidepressants, I'm talking about your 9 opinion with respect to Prozac, Fluoxetine 10 Hydrochloride and whether or not that causes 11 suicidality. Now, in May of 1988 when you came 12 to Eli Lilly, isn't it true that you had the 13 opinion that Prozac didn't cause suicidality, yes 14 or no? 15 MR. MYERS: Once again, Doctor, you 16 need not answer yes or no. If you can, do that, 17 but if you can't, you need not follow Mister 18 Smith's direction. 19 A. When I returned to Lilly in 20 1988, I don't recall how I felt, but as I best 21 would recollect it would be that it would -- that 22 would not be possible that there would be a 23 causal relationship. 24 Q. So when you came to Lilly, you Page 606 1 felt it was not possible that Prozac could have a 2 causal relationship to suicidality, correct? 3 A. I think what I said as best I 4 recollect, I would not have thought there would 5 have been a causal relationship between Prozac 6 and suicidality. 7 Q. You've continued to hold that 8 opinion, haven't you? 9 A. I have become more firm in 10 that opinion. 11 Q. Can you conceive, as a 12 clinical research physician and scientist, 13 anything that would change your opinion on 14 whether or not Prozac has a causal relationship 15 between it and suicidality? 16 A. I doubt that there is any 17 study that could be done that could possibly 18 demonstrate a relationship between Fluoxetine and 19 suicidality. 20 Q. And you certainly don't think 21 that you could ever see a 1639 that would on its 22 face demonstrate a relationship between Prozac -- 23 a causal relationship between Prozac and 24 suicidality? Page 607 1 MR. MYERS: I object to the form, I 2 don't know what you mean by a 1639 on its face. 3 Q. The information on a 1639 4 concerning what the reporter got and what 5 information in this three step, as many as 6 fifteen phone call analysis that you make? 7 A. Could you repeat the question 8 or read it back? 9 (QUESTION READ.) 10 A. In my estimation, it would be 11 highly unlikely that there would be that kind of 12 information that would be convincing. 13 Q. What about a rechallenge study 14 where people that were exposed to Prozac and 15 became suicidal were taken off the Prozac and 16 then reexposed to Prozac, and then those 17 individuals were observed in a scientific 18 controlled double-blind manner to determine 19 whether or not the suicidality reappeared in 20 conjunction with the use of the drug? 21 A. That would be, in my 22 estimation -- in my estimation the only possible 23 study. However, there would be limitations to 24 that study. Number one, if the publicity and the Page 608 1 media coverage of such events seems to me to be 2 so deeply ingrained, one has to question the 3 accuracy of a reporter. Secondly, the taking of 4 a medication, particularly in someone who had 5 taken it before, if there was an event that 6 occurred with the medication such as some slight 7 nausea initially or GI distress, that individual 8 may be able to recognize the drug that they are 9 taking so it wouldn't truly be a double-blind 10 study in someone who had some prior exposure. 11 MR. SMITH: We would object to the 12 response to that question -- to that answer, as 13 being non-responsive, all of those past the 14 phrase, yes, that would be the only possible 15 study, as being non-responsive and move that it 16 be stricken. 17 MR. MYERS: Right, well, you asked the 18 question and that was the answer. 19 MR. SMITH: I also object to any 20 editorial comment or sidebar remarks by counsel 21 for the defendant. I also suggest that if I 22 continue to get the self-serving non-responsive 23 answer from this witness, I more than likely am 24 going to not be able to complete this deposition Page 609 1 and/or cause it to be completed under court 2 supervison at the courthouse where I can get some 3 meaningful response from this witness. And I'm 4 cautioning you now, I put up with it for two and 5 a half days, I have a limited amount of time 6 left, the witness is playing games, his entire 7 responses are designed to be self-serving, he's 8 in no way here in any good natured or good faith 9 attempt to give information or respond to the 10 questions. And if it continues, this deposition 11 will not be able to be concluded and -- and more 12 than likely we are going to request that this 13 witness be deposed under court supervision where 14 he would be directed in regard to the 15 responsiveness of his answer. 16 MR. MYERS: Well, that is your 17 interpretation, Mister Smith, and I will tell 18 you, for the record, that I intend not to change 19 any of the objections that I make and I will tell 20 the witness not to change anything that he is 21 doing to answer the questions to the best of his 22 ability. His deposition will be over today and 23 will not be resumed absent a court order. I 24 think we are very much in agreement on that. Page 610 1 (PLAINTIFFS' EXHIBIT NO. 10 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. (BY MR. SMITH) Doctor, would 5 you read Exhibit 10 and say if you can identify 6 it? 7 Let me give you also Exhibit 8 11, that I think if you read the two in context 9 it would make it a little more understandable. 10 (PLAINTIFFS' EXHIBIT NO. 11 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Do you recognize Exhibits 10 14 and 11? 15 A. Yes, sir. 16 Q. It's a Lilly E-mail, is it 17 not? 18 A. Yes, sir. 19 Q. Or printouts of Lilly E-mail, 20 correct? 21 A. Correct. 22 Q. Which is interoffice 23 communication between those of you working in the 24 medical component at Eli Lilly, correct? Page 611 1 A. Yes, sir. 2 Q. It appears, and you have to 3 take 10 and 11 sort of together, they're both 4 dated September 14th, are they not? 5 A. Yes, sir. 6 Q. And then on the back -- yes, 7 they're both dated September 14th, but at the 8 bottom of page one of the Exhibit 10, there is a 9 notation starting September 13th, is there not? 10 A. Yes, sir. 11 MR. BROWN: What year, Paul? 12 MR. SMITH: 1990. 13 Q. And it would appear to me that 14 the tenor of this communication is is that there 15 is going to be a presentation to the Board of 16 Directors at Eli Lilly and Company and/or Doctor 17 Wood, is that right? 18 A. It would be to -- as I best 19 recollect, to the Board of Directors, which would 20 have included Mister Wood. He's not a physician 21 or a Ph.D. 22 Q. Well, you say on the front 23 page of Exhibit 10, under the September 13th, 24 1990 notation, Ray proposed presentation to the Page 612 1 Board, correct? 2 A. That's correct. 3 Q. And the Board that you're 4 talking about there is the Board of Directors of 5 Eli Lilly and Company, correct? 6 A. Yes, sir. 7 Q. And Mister Wood or Wood there 8 is the Chairman of the Board at that time, 9 Richard Wood? 10 A. That's correct. 11 Q. Leigh Thompson has apparently 12 prepared some slides or prepared a presentation 13 to make to the Board of Directors of Eli Lilly 14 and Company, correct? 15 A. As I read this, it appears 16 that there was a presentation for the Board of 17 Directors that Doctor Thompson was responsible 18 for and there appears that there were some 19 specific verbatims that were intended solely for 20 Mister Wood. 21 Q. Yes. And there were some 22 slides being prepared also? 23 A. Yes, sir. 24 Q. What is a verbatim? Page 613 1 A. It's my understanding that a 2 verbatim is the language that one would use in 3 reviewing data, the communication in which the 4 data would be embedded. 5 Q. So it would be the point 6 supported by the data, the English summary or 7 point of the data? 8 A. I think that would be a fair 9 characterization. 10 Q. And apparently there was a 11 preparation for this Board meeting by Doctor 12 Thompson, Doctor Leigh Thompson? 13 A. That's correct. 14 Q. And apparently you and some 15 other people in the medical component were 16 assisting him in that, correct? 17 A. Yes, sir. 18 Q. And I would assume that Dan 19 Masica, Bob Zerbe, Charles Beasley, David Wheadon 20 and Gordon Gilad were involved in this in varying 21 degrees? 22 A. Yes, sir. 23 Q. But Doctor Thompson apparently 24 by looking at this first page of Exhibit 10 had Page 614 1 already shown some proofs to Mister Wood, is that 2 right? 3 A. From the context or content of 4 his message, that would be the case. 5 Q. And he had prepared some 6 proofs based on some information that he had, 7 correct? 8 A. That's correct. 9 Q. And some verbatims that had 10 been printed based on underlying data, correct? 11 A. That's my understanding, yes. 12 Q. You had been given this data 13 and these verbatims and copies of the 14 presentation that Mister -- that Doctor Thompson 15 was going to make to the Board, is that right? 16 A. Yes. 17 Q. And Doctor Thompson had given 18 that to you on Monday? 19 A. I don't recall that I received 20 them on Monday. I can remember it didn't seem to 21 me that the interval between the time we received 22 them and the time we responded was quite as long 23 as he depicted but -- 24 Q. It was a period of time before Page 615 1 that? 2 A. Yes, sir. 3 Q. And in all honesty, Doctor 4 Thompson is a little upset, is he not? 5 A. Yes, sir. 6 Q. He says, Thank you for your 7 comments but they are late, I gave the drafts to 8 Dan and Bob. That's Dan Masica and Bob Zerbe, 9 isn't it? 10 A. That's correct. 11 Q. He said, I gave the drafts to 12 Dan and Bob early Monday morning with the request 13 for them to proof and verify the numbers, paren, 14 the verbatims are just for Mister Wood. Right? 15 A. That's correct. 16 Q. He said, The slides are made, 17 I showed them yesterday afternoon, the proofs 18 have been shown repeatedly to Wood, et al. Wood, 19 et al, being Chairman Wood, correct? 20 A. That would be my 21 understanding, yes. 22 Q. Do you have any idea who he's 23 talking about when he talks about the et als? 24 A. I could make a supposition. Page 616 1 Q. Some other big dogs, right? 2 You know what a big dog is, don't you? 3 MR. MYERS: He may not. 4 A. They would have -- those 5 individuals would most likely be very senior 6 individuals in the corporation. 7 Q. All right. And it goes on to 8 say, I'm not sure that at this date changes can 9 be made in the slides before Monday, correct? 10 A. That's correct. 11 Q. Now, he has by September 14, 12 1990 at 7:31 in the morning seen the bottom of 13 page ten and the bottom of the first page of 14 Exhibit 10 and the second page of Exhibit 10 and 15 the last page of Exhibit 10, right? 16 A. Yes, sir. 17 Q. And that's dated September 18 13th, correct? 19 A. That's correct. 20 Q. And these comments are what he 21 is considering late, is it not? 22 A. Yes, sir. 23 Q. He's already talked to Doctor 24 Wood -- Mister Wood before this, correct? Page 617 1 A. Yes, sir. 2 Q. Whether the comments were 3 late, at least you had -- it appeared that you 4 tried to give his verbatims and the data that he 5 asked you to review a fairly careful analysis, 6 had you not? 7 A. Yes, sir. 8 Q. Had you spent some time 9 reviewing this material? 10 A. As I recall, we did. 11 Q. And put some effort into it? 12 A. As best I recall, yes. 13 Q. And are you -- you say 14 Charles, David and I have reviewed your 15 presentation and offer the following thoughts and 16 comments, correct? 17 A. That's correct. 18 Q. And you're talking about 19 Charles Beasley? 20 A. Correct. 21 Q. And David Wheadon? 22 A. Correct. 23 Q. And they're asking you to -- 24 you all, the three of you worked on this and then Page 618 1 you were assigned the task of getting back to 2 Doctor Thompson, correct? 3 A. Yes, I was. 4 Q. And you did get back to Doctor 5 Thompson at 17:50 on September 13th, right? 6 A. That's correct. 7 Q. What is 17:50 in American 8 time? 9 A. That's 5:50 p.m. 10 Q. What did you have before you 11 when you made this review, slides, did you have 12 the slides or at least what the slides were going 13 to be? 14 A. I have a recall that we did 15 see, not the slides themselves but hard copies of 16 the slides and hard copies of the verbatims to 17 the best of my recollection. 18 Q. Was there a written text of a 19 presentation? 20 A. There may have been but I 21 don't recall that I can say with certainty that 22 there was. 23 Q. Down at the bottom of page one 24 of Exhibit 10, you have a comment with respect to Page 619 1 verbatim number four, do you not? 2 A. I do. 3 Q. And you say, and this is a 4 verbatim that is going to be presented to the 5 Board of Directors of Eli Lilly and Company, 6 isn't it? 7 A. That's correct. 8 Q. And in the comment of this 9 presentation or the content of this presentation 10 is suicide and its relationship with Prozac, 11 isn't it? 12 A. I believe the -- I do not know 13 the title but I think the thrust of the 14 presentation would be on suicidality in general 15 and then specifically what has been seen, what 16 has been done, with Fluoxetine specifically. 17 Q. The Board was concerned or 18 Doctor Thompson was going to have to make a 19 presentation to the Board in connection with the 20 relationship of Prozac and suicide, wasn't he? 21 A. I believe to the best of my 22 recollection that was a presentation to provide 23 information to the Board of whom few of them 24 would have a little understanding of suicidality, Page 620 1 given the nature of their chosen profession. So 2 it would be an informational presentation and 3 review of the data available as best I 4 understand. 5 Q. But the interest is whether or 6 not the data available and the presentation was 7 directed toward, since it was the Board of 8 Directors at Eli Lilly and Company, was directed 9 toward the relationship between Prozac and 10 suicidality, wasn't it? 11 A. I was not a part of those 12 discussions that would say this was the 13 objective. I think that's a reasonable 14 assumption. 15 Q. All right. Specifically, 16 verbatim four you say, we feel that caution 17 should be exercised in a statement that 18 suicidality and hostile acts in patients taking 19 Prozac reflect the patient's disorder and not a 20 causal relationship to Prozac, correct? 21 A. That's correct. 22 Q. Then you go on to say, 23 Post-marketing reports are increasingly fuzzy and 24 we have assigned a yes, reasonably related, on Page 621 1 several reports. Correct? 2 A. That's correct. 3 Q. Do you know if Doctor Thompson 4 changed his presentation to reflect your comment 5 on verbatim four? 6 A. May I review this once again 7 to see if it may be imbedded in this? 8 Q. Yes. 9 A. There's part of this that is -- 10 I can't read, it's blacked out, so I don't know 11 what may be in that part of the copy that I have. 12 I cannot say from this with certainty that that 13 was changed. There would appear to be some 14 change that he made in which on the second page 15 of this response on slide 1052 in which he may 16 have -- may have incorporated the suggestion we 17 made. 18 Q. Where it says, And Prozac 19 probably reflect the patient's disorders and not 20 a clear causal relationship to Prozac? 21 A. That may be where our response 22 to his verbatim was included in his presentation. 23 Q. You weren't there at the 24 presentation? Page 622 1 A. I was not, sir. 2 Q. And you don't know exactly 3 what he did, do you? 4 A. I do not. 5 Q. And of coarse the proofs or at 6 least -- yes, the proofs and the verbatims had 7 already been shown to the Chairman of the Board 8 as originally drafted before you ever saw them, 9 hadn't they? 10 A. Based upon this communication, 11 yes. 12 Q. Because he says the comments 13 are late, I gave the drafts to Dan and Bob early 14 Monday morning, he says the slides are made, I 15 showed them yesterday afternoon, the proofs have 16 been shown repeatedly to Wood, et al, correct? 17 A. That's correct. 18 Q. Your statement reflected at 19 the bottom of page one of Exhibit 10 was correct 20 at the time, wasn't it, Doctor, where you say 21 post-marketing reports are increasingly fuzzy and 22 we have assigned yes, reasonably related on 23 several reports? 24 A. To the best of my Page 623 1 recollection, that is correct at the time. 2 Q. Go to page two of Exhibit 10. 3 Page two of Exhibit 10 continues your comments 4 with respect to the verbatims of Mister Leigh 5 Thompson -- Doctor Leigh Thompson, that are going 6 to be shown to the Board of Directors of Eli 7 Lilly and Company, correct? 8 A. Correct. 9 Q. And that have already been 10 shown to the Chairman of the Board of Eli Lilly 11 and Company, Mister Wood, correct? 12 A. As far as I know, yes. 13 Q. You were commenting on 14 verbatims on the first page and then it looks 15 like you're commenting on page numbers, doesn't 16 it? 17 A. It does appear that way. 18 Q. Do you recall having a paged 19 text that you were reviewing? 20 A. I have some recollection that 21 there was a text. 22 Q. I've never seen the text. Was 23 that text in your file at some point? 24 A. I don't know that it was in my Page 624 1 file, no. 2 Q. Well, you had the text, had to 3 have had the text at one time to make the 4 comments you made, wouldn't you? 5 A. That's correct. 6 Q. And you're telling me you 7 don't know whether you kept them, maintained them 8 in your file or not? 9 A. I suspect what I did is I 10 corrected the text and returned the text to him. 11 Q. See, we got this from your 12 file, Exhibit 10 from your file, the E-mail. So 13 don't you think it would be likely that the text 14 itself would be in your file if you'd have kept 15 the E-mail? 16 A. No, not necessarily. 17 Q. Okay. Look under about the 18 middle of the page before that dark spot. And by 19 the way, those dark spots are how they came to 20 us. About the middle of the page under page 21 five, you say -- page five, under suicidal 22 thinking in clinical trials, correct? 23 A. That's correct. 24 Q. Apparently you were reviewing Page 625 1 something that had been written in connection 2 with the occurrence of suicidal thinking in 3 clinical trials, right? 4 A. To the best of my 5 recollection, that would have been something that 6 Doctor Thompson had written that addressed that. 7 Q. All right. And you say, 8 quote, you may want to note that trials were not 9 intended to address issue of suicidality. Also 10 in paragraph two, patients were excluded who were 11 serious suicidal risks, end quote, correct? 12 A. That's correct. 13 Q. Was that comment that you made 14 ever incorporated to the Board of Directors of 15 Eli Lilly and Company? 16 A. May I look at the Exhibit 11 17 then? 18 Q. Yes. That's why I gave it to 19 you so you could look at it. 20 A. Thank you. In this 21 communication, with the exception of the part 22 that I cannot read because of the blacking, he 23 does not communicate that he made that change, 24 that does not mean that he didn't. Page 626 1 Q. I understand, but you don't 2 know, you weren't there at the Board of Directors 3 meeting, were you? 4 A. Correct. 5 Q. You weren't invited to 6 participate? 7 A. No. 8 Q. Sit in? 9 A. No, sir. 10 Q. Observe? 11 A. No, sir. 12 Q. Was that a closed meeting of 13 the Board of Directors or was it open? 14 A. Open meaning? 15 Q. Open to shareholders. 16 A. You mean generally 17 shareholders as opposed to -- most board members 18 are shareholders. You're talking an open meeting 19 where anybody that wanted to come in could listen 20 to that meeting? 21 Q. Yes. 22 A. That was a closed meeting as 23 far as I know under that definition. 24 Q. Was it limited only to Page 627 1 individuals who were shareholders of Eli Lilly 2 and Company who had been elected to the Board of 3 Directors? 4 A. I don't know that. 5 Q. But a Board of Directors 6 meeting is a meeting of those people who own 7 stock in a company who are elected to serve as 8 directors of that company by the other 9 stockholders, are they not? 10 A. I don't know that all those 11 individuals hold stock, but most of them do. I 12 don't track that. But they are elected by the 13 share owners to serve in that position. 14 Q. It appears from looking at 15 page five -- looking at your notes on Exhibit 10 16 on the second page, that Doctor Thompson had made 17 some comments about suicidal thinking in the 18 clinical trials, doesn't it? 19 A. It does. 20 Q. And that he had made some 21 comment to Mister Wood about that earlier? 22 A. I cannot be sure that that 23 specifically was included in the verbatims he 24 shared with him, it's likely it's possible. Page 628 1 Q. All right. But he was going 2 to make some presentation to the Board about 3 suicidal thinking in the clinical trials, 4 correct? 5 A. From this communication and 6 from the verbatims, it would certainly appear 7 that that was going to be a component of that 8 presentation. 9 Q. He's talking about the Prozac 10 clinical trials too, isn't he? 11 A. Yes, sir. 12 Q. And he said you say to him in 13 response to whatever he was saying to the Board 14 of Directors and to the Chairman of the Board of 15 Directors, you may want to note that trials were 16 not intended to address the issue of suicidality, 17 also in paragraph two, patients were excluded who 18 were serious suicidal risks, correct? 19 A. That's correct. 20 Q. Was that correct at the time? 21 A. To the best of my knowledge it 22 was correct which -- I'm sorry, let me backtrack. 23 Which was correct? I'm not -- which one are you 24 asking? Page 629 1 Q. Is it correct that the 2 clinical trials on Prozac were not intended to 3 address the issue of suicidality? 4 A. Those were not stated 5 objectives of the trials, that was not the intent 6 of those trials. 7 Q. Doctor, we were talking this 8 morning concerning the conservative approach that 9 was formulated by members of the medical 10 component and members of the legal staff at Lilly 11 in connection with reporting adverse reactions 12 with respect to Prozac. Do you recall that? 13 A. I recall that discussion. 14 Q. Do you recall it was your 15 statement then that the policy of Lilly was to be 16 as conservative as possible in this regard? 17 A. As best I recall, our 18 instructions were to be very conservative in 19 reporting events. 20 Q. Is it your opinion that Lilly 21 should be as conservative as possible in 22 reporting adverse events? 23 A. Yes. 24 Q. And is it your opinion that Page 630 1 Lilly should be as conservative as possible in 2 dealing with adverse events in connection with 3 the use of Prozac? 4 A. I think it's important to be 5 conservative in the review of events that have 6 been reported to occur. 7 Q. Do you think it's important 8 that Lilly be conservative and is it Lilly's 9 policy to be conservative in their relationship 10 with Prozac and its safety to the general public? 11 A. It is my impression that we 12 have been conservative and balanced in the review 13 of safety data and what we communicate to the 14 prescriber. 15 Q. In other words, what you 16 communicate to the prescriber should be 17 communicated in the most conservative fashion? 18 A. In a conservative and balanced 19 fashion. 20 Q. Yes, consistent with patient 21 safety? 22 A. That's correct. 23 Q. Because I believe we have a 24 memo somewhere that we've already introduced in Page 631 1 evidence where you expressed the concern for 2 safety of the patient. I'm not trying to trick 3 you, Doctor, it's in your memo. 4 A. I'm trying to think of the 5 particular exhibit. 6 (WITNESS REVIEWS EXHIBIT.) 7 A. Yes, that's right. 8 Q. And in communicating risk, 9 it's your judgment that Lilly should be as 10 conservative as possible consistent with patient 11 safety. 12 A. I think we should be 13 conservative and balanced at all times. 14 Q. What do you mean by balanced? 15 A. I think one has to provide 16 information which reflects the best scientific 17 thinking to -- in one's communications to the 18 providers and utilizers of health care. 19 Q. And if there's a question as 20 to what that balance should be, then Lilly should 21 be as conservative in presenting that scientific 22 matter as is possible to prescribers of the drug? 23 A. You're asking for my opinion? 24 Q. Yes. Page 632 1 A. Yes, I would agree with that. 2 (PLAINTIFFS' EXHIBIT NO. 12 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. I don't know that it's 6 necessary that you read the entire document, 7 Doctor. You can read the entire document, it's 8 the German package insert prescribing 9 information. I'm not going to talk about every 10 sentence of every page. 11 MR. MYERS: Is there a part you would 12 like him to focus in on and read? 13 MR. SMITH: Yes, and I'll point that 14 out to him after he's familiar with it. 15 A. Okay. 16 Q. I'm just saying you don't need 17 to -- I'm not going to ask you fact and figure 18 questions about each and every indication there. 19 A. I have scanned the exhibit. 20 Q. Doctor, what's been marked as 21 Exhibit 2 -- 12, is a translation of the package 22 insert for Prozac, Fluoxetine Hydrochloride in 23 Germany, correct? 24 A. That appears to be the case. Page 633 1 Q. And in Germany, Prozac is 2 known as Fluctin, is it not? 3 A. Yes, sir. 4 Q. And Fluctin in Germany is 5 exactly the same thing as Prozac is in the United 6 States? 7 A. Yes, sir. 8 Q. There's no difference in the 9 chemical compound of Fluctin and Prozac? 10 A. Not that I'm aware of. 11 Q. And if you were a physician in 12 Germany, if you wanted to write somebody a 13 prescription for Prozac, you would write that 14 prescription using the word Fluctin, correct? 15 A. That's correct, sir. 16 Q. But you would get Prozac, 17 Fluoxetine Hydrochloride, correct? 18 A. Yes, sir. 19 Q. It's Fluoxetine Hydrochloride 20 whether you call it Prozac or you call it 21 Fluctin? 22 A. That's correct. 23 Q. In looking at the back page of 24 this document, it appears that this is the Page 634 1 package insert for, and it's dated March 16, 2 1992, correct? 3 A. Yes, sir. 4 Q. Then above that date, it says 5 Lily Deutschland, Limited, Giessen, correct? 6 A. Yes, sir. 7 Q. Is that the German affiliate 8 of Eli Lilly and Company? 9 A. I don't know if that's the 10 German affiliate, I would suppose that to be the 11 case. 12 Q. Well, it's got an address in 13 Hamburg, Germany, doesn't it? 14 A. Pardon? 15 Q. It has an address in Hamburg, 16 Germany, doesn't it? 17 A. As I read that, there are two 18 components, one in Giessen and one in Hamburg, 19 and the Hamburg would be Byersdorf Lilly and the 20 one in Giessen would be Lily Deutschland. So 21 there's two different components. 22 Q. But they're both Eli Lilly 23 names and affiliates in Germany, aren't they? 24 A. I would suppose that to be the Page 635 1 case, I've never dealt with the German. 2 Q. This is not a trick. 3 A. No, but I just want to be as 4 accurate in terms of the degree of familiarity I 5 had with the affiliates outside the United 6 States. 7 Q. You even met with these German 8 affiliates, haven't you? 9 A. I haven't been to the German 10 affiliate. 11 Q. They've been here and you've 12 met with them, haven't you? 13 A. I have met with select people 14 at various times from the German affiliates. 15 Q. You worked in the DEN data 16 base with them? 17 A. That would be correct. 18 Q. They're giving Fluctin-Prozac 19 and marketing Fluctin-Prozac in Germany, correct? 20 A. That's correct. 21 Q. There's not been any 22 difference that has been found, has there, in the 23 reaction that German individuals have to 24 Fluctin-Prozac in Germany that we Americans have Page 636 1 to Prozac in the United States of America, has 2 there? 3 A. I'm not aware of differences 4 in events that have been reported. 5 Q. We're human beings throughout 6 the world, correct? 7 A. I would agree. 8 Q. Red, yellow, black and white, 9 we're all children in his sight, correct? 10 A. That's correct. 11 Q. And Prozac, Fluctin works 12 biochemically in Germany just like Prozac works 13 in we in America, correct? 14 A. Substantially the same. There 15 may be in various ethnic groups or racial groups 16 some slight differences that I would not be aware 17 of but I would agree with your statement in the 18 broad context of how you stated it. 19 Q. You don't know that Prozac has 20 from some ethnic or racial sense is more likely 21 to produce suicide in Germany, in German 22 individuals than Prozac is in -- produce suicide 23 in United States American citizens? 24 MR. MYERS: I object to the form of Page 637 1 the question. Answer it, if you can. 2 A. What -- how I would respond to 3 that is that there's no evidence that the event 4 of suicidality occurs more frequently in either 5 population. 6 Q. And Germans and Americans are 7 both human beings? 8 A. Yes, sir. 9 Q. We both have serotonin 10 systems? 11 A. Yes, sir. 12 Q. We both get hungry and eat and 13 sleep and are happy and sad, right? 14 A. That's correct. 15 Q. Homo sapiens, there are in 16 Germany, right? 17 A. Correct. 18 Q. You're not going to tell me 19 that Prozac works differently on Americans than 20 it does on Germans, are you? 21 A. No, I'm not. 22 Q. You've not seen anything that 23 would in the slightest way indicate that this 24 drug works chemically differently in Germans than Page 638 1 it does in Americans? 2 A. That's correct, correct, yes, 3 sir. 4 Q. Now in connection with this 5 conservative approach that you're talking about 6 with Lilly, look please on page two of the 7 package insert, which would be page three of the 8 exhibit, where it talks about risk patients. Do 9 you see that? 10 A. Page two? 11 Q. Yes. 12 A. Yes, sir. 13 Q. It says risk patients, and 14 then under that it says risk of suicide. Do you 15 see that? 16 A. Yes, sir. 17 Q. Fluctin, Prozac, right? 18 A. That's correct. 19 Q. Fluctin does not have a 20 general sedative effect on the central nervous 21 system. Therefore for his/her own safety, the 22 patient must be sufficiently observed until the 23 antidepressant effect of Fluctin sets in. Taking 24 an additional sedative may be necessary. This Page 639 1 also applies in cases of extreme sleep 2 disturbances or excitability. End quote. Is 3 that what it says, Doctor? 4 A. Yes, sir. 5 Q. That's not what the United 6 States package insert says, is it? 7 A. Not to my knowledge. 8 Q. The United States package 9 insert does not say Prozac does not have a 10 general sedative effect on the central nervous 11 system, does it? 12 A. Would you repeat that? 13 Q. The package insert in the 14 United States does not say Prozac does not have a 15 general sedative effect on the central nervous 16 system, does it? 17 A. I would have to review that 18 just to be sure of the language, but I assume 19 that's correct if that's what you're telling me. 20 Q. The package insert, the 21 product's dispensing information in the Prozac 22 package in the United States does not say 23 therefore for his or her own safety the patient 24 must be sufficiently observed until the Page 640 1 antidepressant effect of Fluctin or Prozac sets 2 in, does it? 3 A. Not to my knowledge. 4 Q. The United States package 5 insert, that prescribing information for doctors 6 in this country, does not say like it says in 7 Germany taking an additional sedative may be 8 necessary, does it? 9 A. Not that I recall. 10 Q. The United States package 11 insert for doctors prescribing medications or for 12 people taking Prozac in the United States of 13 America does not say this also applies in cases 14 of extreme sleep disturbances or excitability, 15 does it? 16 A. Not that I recollect. 17 Q. Don't you think, Doctor, that 18 to take the most conservative approach with 19 respect to the risk of suicide and Prozac that 20 the German package insert is preferable to that 21 of the United States package insert? 22 MR. MYERS: Before you answer, Doctor, 23 let me object to the form of the question to the 24 extent you're trying to draw a comparison or some Page 641 1 equation between the two inserts. That's a 2 matter of United States and German regulatory 3 law. If you can answer the question, go ahead. 4 A. No. 5 Q. Do you not agree that this is 6 a good item to have in the package insert in 7 Germany? 8 MR. MYERS: Same objection as to the 9 form. Go ahead and answer if you can. 10 A. It would -- again this would 11 be language that would have been worked through 12 the German regulatory authorities relative to the 13 standards of care within Germany. 14 Q. I'm not talking about Germany, 15 Doctor, I'm talking about the conservative 16 approach and Lilly's policy. I don't care about 17 any regulatory bodies. I'm talking about the 18 differences in these two package inserts. Don't 19 you think this is a better package insert 20 personally -- 21 A. No. 22 Q. Let me finish my question. In 23 connection with the risk of suicide and the use 24 of Prozac? Page 642 1 MR. MYERS: Same objection. Go ahead. 2 A. No, I don't. 3 Q. And that's because you from 4 the very start never thought, never held an 5 opinion and still don't hold the opinion that 6 Prozac presents any risk for suicide in 7 individuals? 8 A. No, that's incorrect. 9 Q. Oh, you do believe that Prozac 10 presents a risk of suicide for individuals? 11 A. No, I disagreed with your 12 initial statement. 13 Q. What initial statement? 14 A. That you stated that that's 15 the way I've always felt and that's why I respond 16 to that particular question about this particular 17 language in the way that I did. 18 Q. Did you at some point feel 19 that Prozac presented a risk of suicide for some 20 individuals? 21 A. No, I don't. 22 Q. Okay. 23 A. In my estimation, no. 24 Q. Then does that explain why you Page 643 1 don't feel that this is the better, more 2 conservative approach to dealing with this 3 problem? 4 MR. MYERS: Same objection. 5 A. It's my impression that both 6 inserts, as best I recollect, are equally 7 conservative. 8 Q. Well, the best you recollect, 9 does the package insert in the United States say 10 anything about the fact that Prozac doesn't have 11 a general sedative effect on the central nervous 12 system? 13 MR. MYERS: I object, that's been 14 asked and answered. Answer it again. 15 A. To the best of my 16 recollection, I don't know whether that statement 17 is in the package language or not, I'd have to 18 see the package insert. 19 Q. I thought you were familiar 20 with the package insert and you had to be in 21 order to perform your duties as a clinical 22 research physician because you got to know 23 whether or not there's any adverse experiences 24 that have been reported with the drug so you Page 644 1 could make a determination with respect to 2 whether or not they are expected or unexpected. 3 MR. MYERS: I object to the form. He 4 didn't say he wasn't familiar with the insert. 5 A. I am familiar with the insert, 6 I do refer to it frequently for the specifics of 7 language. 8 Q. Okay. Then don't you remember 9 that the insert in the United States doesn't say 10 a whit about Prozac does not have a general 11 sedative effect on the central nervous system? A 12 whit is anything in Texas language. 13 MR. MYERS: Asked and answered. 14 Answer it one more time, Doctor. 15 A. I would need to see the 16 package labeling to refresh my memory. 17 Q. You don't have any 18 recollection at all, Doctor, what the United 19 States package insert says with respect to 20 whether or not Prozac has a sedative effect on 21 the central nervous system? 22 MR. MYERS: Don't answer that, Doctor, 23 you've answered that four times. Ask him another 24 question, Paul, he's not going to answer that Page 645 1 question again. 2 MR. SMITH: Certify that question. 3 (QUESTION CERTIFIED.) 4 MR. MYERS: You'll find three or four 5 answers to it in the transcript. 6 Q. Does it say anything about 7 Prozac having a general sedative effect in that 8 portion of the package insert that deals with 9 suicide in the United States? 10 A. I don't know. 11 Q. Can you tell me one word of 12 what the package insert in the United States says 13 about suicide? 14 A. As best I recollect, there is 15 a statement relative to the care that must be 16 taken in the prescribing of a medication for 17 depression and a vague recollection of monitoring 18 one's illness. 19 Q. Is that because in your 20 opinion -- is that there because Prozac presents 21 a risk of suicide? 22 A. No. 23 Q. Is it your opinion that that 24 package insert in the United States warrants that Page 646 1 patients should be observed because Prozac maybe 2 presents a risk of suicide to United States 3 Americans? 4 A. I think that statement is in 5 the package labeling because depression 6 represents a risk for suicide, not Prozac. 7 Q. So that's not a statement 8 about the risk of Prozac and suicidality? 9 A. That's correct, to the best of 10 my knowledge. 11 Q. So back to it, that United 12 States package insert doesn't say anything in 13 that suicide section concerning Prozac not having 14 a general sedative effect? 15 A. Not that I recall. 16 Q. All right. And certainly that 17 package insert in the United States doesn't 18 recommend an additional sedative in connection 19 with patients who have a risk of suicide, does 20 it? 21 A. Not to my knowledge. 22 Q. Do you think that this warning 23 or this information that's contained in the 24 German package insert is misleading? Page 647 1 A. I think that is information 2 that to the best of my knowledge reflects as to 3 how German physicians and German psychiatrists 4 treat their depressed patients. 5 Q. That's not what I asked you at 6 all, is it? 7 A. Would you repeat the question? 8 Q. Is there anything about this 9 language in the risk of suicide section of the 10 German package insert that is misleading? 11 A. Not in the context of the 12 German setting. 13 Q. Well, is it misleading in the 14 United States, in the context of the United 15 States setting? 16 MR. MYERS: Let me object to the form 17 of the question again on the grounds that that is 18 an insert, a U.S. insert of regulatory documents. 19 Go ahead and answer, Doctor. 20 A. Would you repeat the question, 21 again? 22 (QUESTION READ.) 23 A. I think it would be somewhat 24 misleading, yes. Page 648 1 Q. So you don't think it should 2 be used in the United States? 3 A. My sense is that the use of 4 sedatives in the United States is different than 5 it is in Germany so that it would not be 6 appropriate in this setting where individuals may 7 feel that sedatives would be recommended for a 8 depressed patient would be -- have any additional 9 efficacy or benefit to the patient. 10 Q. Are you telling me that a 11 patient, an individual suffering from depression 12 in Dallas, Texas reacts to a sedative differently 13 than a patient in Hamburg, Germany? 14 MR. MYERS: I object to the form, 15 that's not what he said. 16 A. No, that's not what I said. 17 Q. They react exactly the same, 18 don't they? 19 A. They should have the same 20 response, yes. 21 Q. Because we're humans, I 22 thought we covered that, in both places, aren't 23 we? 24 A. Yes, sir. Page 649 1 Q. So the mechanism of an action 2 of any particular sedative is not going to be any 3 different, is it? 4 A. That's correct. 5 Q. Anything else you see about 6 this that's misleading, in your opinion? 7 A. I don't think that is 8 misleading, in my opinion. 9 Q. I thought you said it was? 10 A. No. I said this language, if 11 it were applied in the United States would be 12 misleading. 13 Q. Why? 14 A. I don't know there's any 15 substantial documentation that a sedative 16 prescribed early in the course of a treatment 17 with an antidepressant makes any difference in 18 terms of efficacy or outcomes. 19 Q. Oh, is that right? You know 20 Doctor Jan Fawcett, don't you? 21 A. I do. 22 Q. Do you know Doctor Fawcett, 23 have you read his article, Targeting Treatment In 24 Patients With Mixed Symptoms Of Anxiety And Page 650 1 Depression? 2 A. I have not. 3 Q. You've not read that? 4 A. I have not. 5 Q. Doctor Fawcett says -- I'll 6 bring it over here. I only -- I just have this 7 one copy, so I'll just have to read it to you. 8 Has Fawcett conducted clinical 9 trials for Eli Lilly and Company? 10 A. To my knowledge, he has. 11 Q. In depression? 12 A. To my knowledge, yes. 13 Q. With Prozac? 14 A. I know his group has for sure. 15 Q. Okay. You see here where 16 Doctor Fawcett writes, aggressive treatment with 17 a benzodiazepam anoloxic is indicated for 18 immediate relief of anxiety in patients with 19 major depression if they manifest risk factors of 20 suicide -- for suicide, if anxiety is severe or 21 if the antidepressant selected causes 22 jitteriness, paren, Fluoxetine, close paren, or 23 is without sedative properties, paren, 24 Desipramine, Imipramine, Buproprine, close paren. Page 651 1 Do you agree or disagree with that? 2 MR. MYERS: Before he answers, let me 3 object to the form of the question. You read him 4 about four lines out of a multiple page document 5 that he's not reviewed or had an opportunity to 6 review. If you're able to answer, Doctor, go 7 ahead and answer. 8 MR. SMITH: In connection with the 9 objection lodged by defense, let the record 10 reflect that the document was produced to us by 11 Eli Lilly as stamped on its face. 12 MR. MYERS: So what? 13 MR. SMITH: So, it's groovy. 14 MR. MYERS: As Judge Dillon would say, 15 so what. 16 A. I don't know that I can really 17 make a comment on this without putting it in the 18 full context of Doctor Fawcett's paper. 19 Q. Okay. Why don't you read that 20 article sometime, Doctor, that way you can 21 comment on that, that way you might have a better 22 understanding of maybe why the German government 23 suggests use of a sedative in connection with 24 certain patients taking Prozac, correct? Page 652 1 MR. MYERS: Don't respond to that, 2 Doctor. And don't lecture him, Paul. 3 Q. So I understand your testimony 4 correctly, Doctor, do you have an opinion 5 concerning whether or not the German package 6 prescribing information is better, the same or 7 worse than as far as describing the risk of 8 suicide in patients taking Fluoxetine than that 9 package insert that we have in the United States 10 of America? 11 MR. MYERS: I object to the form on 12 the grounds I earlier stated. Go ahead and 13 answer if you can. 14 A. In my estimatation, they're 15 equally conservative. 16 Q. So you wouldn't have any 17 objection, since they're equally conservative, 18 with this information being transmitted to 19 physicians in the the United States of America, 20 this German information? 21 MR. MYERS: Same objection as to the 22 form. 23 A. I would have concerns given 24 that I am unaware of any documentation that shows Page 653 1 that the addition of a sedative or hypnotic 2 substantially improves one's treatment of 3 depression in the general depressed population. 4 Q. How about it improving a 5 person's chance of not committing suicide who is 6 depressed? 7 A. I'm not sure that that 8 intervention prevents an individual from 9 committing suicide. 10 Q. Well, are you criticizing the 11 concomitant use of sedatives and Prozac? 12 A. What I'm saying is that I 13 think that the concomitant use for depression in 14 Germany and the United States is different. 15 Q. Well, but see I don't 16 understand that, Doctor, because isn't it true 17 that you use sedatives, tranquilizers and 18 sleeping pills on those individuals who happen to 19 participate in the Lilly clinical trials when you 20 were trying to get FDA approval of this drug? 21 A. Selected sleep inducing agents 22 were permitted in those trials. 23 Q. So what's your criticism of 24 using a sedative in connection with prescribing Page 654 1 Prozac in context of that package insert? 2 A. I have no objection. 3 Q. All right. So you wouldn't 4 have any objection to this package insert being 5 used in the United States of America? 6 MR. MYERS: Object to the form and 7 it's been asked and answered a couple of times. 8 Go ahead and state it one more time for Mister 9 Smith. 10 A. The treatment of depression 11 varies from country to country and it varies from 12 Germany and the United States. Given the wording 13 of this particular insert, I would have no 14 substantial objection as I see it and read it 15 provided the balance is provided relative to the 16 information which is known and prescribing 17 practices of physicians in the United States. 18 Q. What if we added this German 19 package insert and put it right there in 20 connection with the United States package insert 21 where it says suicide, wouldn't that be better? 22 MR. MYERS: Let me object to the form 23 of the question again on the grounds of the 24 package insert is a regulatory document governed Page 655 1 by law. 2 MS. ZETTLER: Are you saying that 3 there's something in the regulations preventing 4 them, Larry, from putting that language into the 5 U.S. package insert? 6 MR. MYERS: I'm not testifying about 7 anything, I'm just making an objection. 8 MR. SMITH: We're just asking you for 9 your legal opinion since you're making such an 10 objection. 11 THE WITNESS: I think I need to have 12 it reread if possible. 13 MR. MYERS: You want the question 14 again, Doctor? 15 THE WITNESS: Yes. 16 (THE COURT REPORTER READ BACK THE 17 REQUESTED TESTIMONY.) 18 A. I do not know that it would be 19 better. It might be, might not be, I can't make 20 that definitive statement. 21 Q. (BY MR. SMITH) What if you 22 were going to use the most conservative approach, 23 it would be better, wouldn't it? 24 A. Not necessarily, I think Page 656 1 they're both conservative package inserts. 2 Q. If you were going to use both, 3 it would be doubly conservative, wouldn't it? 4 MR. MYERS: Objection to the form. 5 Paul, he's answered that question a couple of 6 times. Go on to something else. 7 Q. We were talking yesterday, 8 Doctor, about the dosage of Prozac. 9 A. Yes, sir. 10 Q. Do you remember? And I 11 believe it was your testimony, and correct me if 12 I'm wrong, that you cannot tell whether or not 13 Prozac was at a therapeutic level by measuring 14 blood samples, is that correct? 15 A. That's correct. 16 Q. And that the only way to tell 17 whether or not Prozac is on board at a 18 therapeutic level is by observing behavior? 19 A. A clinical assessment, yes. 20 Q. Do you acknowledge, Doctor, 21 that there is a great deal of -- that there were 22 clinical studies in connection with different 23 dosage of Prozac? 24 A. Yes, sir. Page 657 1 Q. And that there were findings 2 in those clinical studies that higher dosage of 3 Prozac was more likely to cause adverse events 4 than lower dosage? 5 A. I recall that there were some 6 events which occurred with greater frequency at 7 higher doses and lower doses, yes, sir. 8 Q. Therefore, is the answer to my 9 question yes? 10 A. I'm saying yes, that there 11 were more events observed. Not necessarily would 12 those be considered adverse events, they would be 13 events reported during the clinical trials and I 14 don't know how you define adverse, whether you're 15 implying causality or not. I'm saying there 16 would be more events reported with a higher dose 17 than a lower dosage for some events. 18 Q. Well, I'm using adverse events 19 in the term that you use ADE throughout your 20 writings and your studies. Have we got some 21 problem on a definition now? 22 A. I just want to be sure that 23 when we discuss adverse events we're talking 24 about events that occurred during a trial or Page 658 1 during an individual's utilization of a given 2 compound, be it Fluoxetine or placebo. 3 Q. Is it not true, Doctor, that 4 the clinical trials reported a greater incidence 5 of adverse events in those clinical trials where 6 patients were taking the higher dosage as opposed 7 to that same trial where patients were taking 8 lower dosage? 9 A. I believe there were some 10 events that occurred statistically more often but 11 I could not recall those specific events. 12 Q. I understand, I'm just asking 13 the general question, that there were occasions 14 when there were greater adverse events at a 15 greater dosage? 16 A. To the best of my 17 recollection, yes, sir. 18 (PLAINTIFFS' EXHIBIT NO. 13 WAS 19 MARKED FOR IDENTIFICATION AND 20 RECEIVED IN EVIDENCE.) 21 Q. Have you had an opportunity to 22 review Exhibit 13, Doctor? 23 A. I'm just about through. I 24 have now, thank you. Page 659 1 Q. That's a memo dated June 13, 2 1988, is it not? 3 A. That's correct. 4 Q. Up in the upper right-hand 5 corner of the page, it's got your name written in 6 pencil or in handwriting. 7 MR. MYERS: This one is sort of 8 chopped off. 9 A. This is chopped off, I 10 apologize. 11 (COUNSEL HANDS DOCUMENT TO WITNESS.) 12 A. It does, yes. 13 Q. Do you recall seeing this 14 document? 15 A. I don't recall seeing it. 16 Q. It came from your file. 17 A. I don't recollect seeing this 18 particular communication. 19 Q. It's authored by Leigh 20 Thompson, is it not? 21 A. That's correct. 22 Q. The memo is apparently a 23 detailed trip report that Doctor Thompson made to 24 a Psychiatrist Experience Program in Long Beach, Page 660 1 correct? 2 A. That's correct. 3 Q. What is the Psychiatrist 4 Experience Program? 5 A. At the time of the launch of 6 the compound, to the best of my knowledge, Lilly 7 sponsored some psychiatrist experience programs 8 with that title in which data was reviewed as 9 regards efficacy and apparently safety of the 10 compound. 11 Q. It appears that there were 12 some Lilly personnel that made presentations 13 there. 14 A. I do not think that Lilly 15 actually made any presentations, any physicians 16 from Lilly. It would appear that most of those 17 speakers would have been from outside of Lilly. 18 Whether there may have been -- I'm speaking to 19 some extent from my experience and what I 20 recollect, there would not have been a Lilly 21 speaker. 22 Q. Okay. Well, they were at 23 least, Doctor Thompson says, Do the panelists -- 24 on the top of the second page, Doctor Thompson Page 661 1 says, Do the panelists study our product 2 monograph and CIB, they seem unaware of much of 3 the data and misstated numerous minor facts. Do 4 you see that? 5 A. Yes, sir. 6 Q. What is the product monograph? 7 A. The product monograph is the 8 document, as best I recollect, that is used in 9 detailing physicians. 10 Q. What is the CIB? 11 A. That is the clinical 12 investigators brochure. 13 Q. Okay. The clinical 14 investigators brochure is not something that is 15 distributed to physicians generally, is it? 16 A. No, it's not. 17 Q. As a matter of fact, it's just 18 distributed to your clinical investigators, isn't 19 it? 20 A. That's correct. 21 Q. So that's why I thought that 22 these speakers were associated with Lilly in some 23 way because it says they have our -- the 24 panelists study our product monograph and Page 662 1 clinical investigators brochure, correct? 2 A. That's correct. But I would 3 not -- in my experience and from my 4 recollections, I do not recall that on the panel -- 5 that in the formal program there was a Lilly 6 speaker identified in those psychiatrist 7 experience programs. I don't know why Doctor 8 Thompson suggested that these individuals should 9 have the CIB unless they had been or were 10 investigators. 11 Q. That's not impossible, is it, 12 that you would have some panelists speaking that 13 were investigators? 14 A. That would be possible. 15 Q. Because Doctor Dunner is one 16 of your investigators and also a member of your 17 Psychiatric Advisory Board, isn't he? 18 A. He has been an investigator 19 and he has been a member of the advisory board. 20 I'm not sure what the constellation of that board 21 is at this time. 22 Q. Read for me the -- read with 23 me the first sentence of the second paragraph of 24 that document. It says there is tremendous Page 663 1 pressure from the gurus and practicing 2 psychiatrists to make ten milligram or even five 3 milligrams available, doesn't it? 4 A. That's exactly what it says. 5 Q. And that was back in 1988, 6 wasn't it? 7 A. Yes, sir. 8 Q. Were you aware in 1988 that 9 gurus and practicing psychiatrists were desiring 10 that Lilly make a ten milligram dosage of Prozac 11 available? 12 A. I recall that indeed they 13 were. 14 Q. But it was not being made in 15 the pulvule form in June of 1988, was it? 16 A. I'm sorry? 17 Q. In ten milligrams? 18 A. Correct, it was not. 19 (PLAINTIFFS' EXHIBIT NO. 14 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 Q. Read Exhibit 14. 23 A. I've read this, I reviewed it. 24 Q. This is a meeting you attended Page 664 1 eighteen months after Doctor Thompson's memo, 2 correct? 3 A. That's correct. 4 Q. And you went to a meeting in 5 Vienna? 6 A. Yes, sir. 7 Q. What did they do, because you 8 were late on your analysis of the September 1990 9 board meeting, sent you to Vienna? 10 A. Is that a question? 11 Q. No, I was teasing you, unless 12 they did. Lilly did send you to Vienna, didn't 13 they? 14 A. Yes, they did. 15 Q. Or did you travel at your own 16 expense? 17 A. I was sent by the company. 18 Q. What was that convention you 19 were at? 20 A. That was a symposium or 21 symposia relative to, I don't remember the exact 22 title but as best I recall at least one day was 23 devoted to Fluoxetine. 24 Q. And were there gurus and Page 665 1 practicing psychiatrists there at that meeting as 2 they were in the meeting described by Doctor 3 Thompson? 4 A. Yes, I would consider some of 5 the European attendees thought leaders. 6 Q. All right. That meeting, at 7 least in the first paragraph, that report was 8 transmitted to Doctor Thompson, Doctor Weinstein, 9 and Zerbe, was it not? 10 A. As the primary addressees, 11 yes. 12 Q. And Doctor Beasley and Doctor 13 Wheadon also received copies of this, did they 14 not? 15 A. Yes, sir. 16 Q. And in November, 1990, you 17 reported, quote, clearly, very clearly there is a 18 need for a lower dose in pulvule form. Five 19 milligrams would be most appropriate, although at 20 the child psychiatry meeting in Chicago, two 21 point five milligrams was suggested. The liquid 22 formulation will only partially address this 23 need. End quote. Isn't that correct? 24 A. That's correct. Page 666 1 Q. You go on to say, we have not 2 established the lowest effective dose and if we 3 listen to the prescribers, some efforts should be 4 made to do this. If not, MDs will continue to 5 dissolve pulvules and will anxiously await new 6 medications with greater flexibility in dosing. 7 You say that, don't you? 8 A. Yes, sir. 9 Q. You also say suicidality is 10 not a big concern at this time in Europe but it 11 may become a concern if there's more media 12 activity. Don't you? 13 A. Yes, sir. 14 Q. Did you know at that time in 15 November, 1990 that the British government would 16 not allow Fluctin-Prozac to be distributed to the 17 citizens of their country? 18 MR. MYERS: I object to the form. 19 Tell him if you know. 20 A. I don't recall. 21 Q. Were there any German 22 psychiatrists there that you recall in Vienna? 23 A. I'm confused. 24 MR. MYERS: You said the British. Did Page 667 1 you mean British? You said British and then you 2 said Fluctin. 3 MR. SMITH: Strike that. If I did say 4 British, I didn't mean to. 5 Q. Did you know at the time, 6 November 7, 1990, that the German government had 7 been requested by Lilly to market Prozac, Fluctin 8 in Germany but that the German government had 9 refused to allow them to do that in November, 10 1990? 11 MR. MYERS: I object to the form. 12 Tell him if you know. 13 A. As best I recall the compound 14 was not approved at that time but I don't have 15 the specific recall of what the date was. 16 Q. Did you know it had been 17 rejected in fact by the German government? 18 MR. MYERS: I object to the form. 19 Tell him if you know. 20 Q. Did you know it had been 21 rejected? 22 A. I don't recall. 23 Q. Did you know that the 24 application to market Prozac in Germany in Page 668 1 November, 1990 had been withdrawn because Lilly 2 had received an intent to reject letter from the 3 German government? 4 A. I don't recall that. 5 Q. And did you know that the 6 German government in their intent to reject 7 letter and in their communications to Lilly had 8 advised Lilly that one of the serious problems 9 with this drug that caused them to issue their 10 intent to reject was that Prozac was activating 11 and they felt it raised a potential for 12 suicidality? 13 MR. MYERS: Before you answer let me 14 object to the form because I don't think you 15 accurately described what happened. But if you 16 know, tell him. 17 A. I'm not aware. 18 MR. SMITH: Let's take a break. 19 (A SHORT BREAK WAS TAKEN.) 20 * * * * * * * * * * 21 CROSS EXAMINATION 22 BY MR. HARRIS: 23 Q. Doctor, my name is Robert 24 Harris and I represent one of the defendants in a Page 669 1 Texas suit that's styled basically Welch versus 2 Eli Lilly, Doctor Neaves, Minith-Meier Clinic, I 3 represent Doctor Neaves and I believe Mister 4 Smith asked you a couple of questions regarding 5 the Welch matter, particularly that he asked you 6 if you reviewed certain Form 1639s or any of that 7 or made an investigation, and I believe that your 8 answers were that you did not remember. In that 9 regard let me ask you these questions: If you 10 had performed an investigation, I assume or I 11 would like for you to respond to whether it would 12 have been in regard to only making a 13 determination about the factors that were 14 reported to the FDA and not factors involving 15 medical treatment. Is that a correct statement? 16 A. That would be a correct 17 statement. 18 Q. And you don't have any 19 personal knowledge of any medical treatment 20 rendered in the Welch case? 21 A. None that I recall. 22 MR. HARRIS: Larry, do we have the 23 same agreement with this witness that he'll not 24 answer questions of standard of care? Page 670 1 MR. MYERS: This witness will not be 2 offered in the trial of this or any other case to 3 give opinions concerning the standard of care in 4 any malpractice related issues. 5 6 Q. (BY MR. HARRIS) In that 7 regard, and it's only peripherally related, I 8 wanted to ask you a question. Earlier you gave 9 an opinion that you believe that there's not a 10 connection between suicide ideation and or 11 suicide and the ingestion of Fluoxetine and I 12 wanted to ask you this: Is that based on a 13 reasonable degree of medical probability? 14 MS. ZETTLER: I object to the extent 15 that I don't know if he's qualified as the -- 16 MR. HARRIS: He's an M.D. and the 17 plaintiffs elicited the opinion from him. 18 MS. ZETTLER: May I finish my 19 objection? I'm not sure that he's qualified in 20 all aspects of clinical science that it would 21 take for him to give an informed opinion, but to 22 the extent that he's not, I'll object. 23 Q. (BY MR. HARRIS) You may 24 answer the question, Doctor. Page 671 1 MR. MYERS: You can answer him. 2 A. Could the question be 3 repeated? 4 Q. Yes, I don't need to read it 5 back. You testified earlier that you had an 6 opinion that there was not a causal connection 7 between the ingestion of Fluoxetine and suicidal 8 ideation or suicide. And my question is, Doctor, 9 was that opinion based on a reasonable degree of 10 medical probability? 11 A. Yes, sir. 12 MS. ZETTLER: Objection. 13 MR. HARRIS: Thank you. No further 14 questions. We'll reserve until time of trial. 15 MS. SMITH: I have no questions at 16 this time. 17 MR. BROWN: No questions. 18 * * * * * * * * * * 19 REDIRECT EXAMINATION 20 BY MS. ZETTLER: 21 (PLAINTIFFS' EXHIBIT NO. 15 WAS 22 MARKED FOR IDENTIFICATION AND 23 RECEIVED IN EVIDENCE.) 24 A. I gather you want me to go Page 672 1 through each page? 2 Q. No, you can just look through 3 it generally. 4 A. I have a general sense of the 5 document. 6 Q. Do you recognize the document 7 that makes up Exhibit 15? 8 A. I recognize certain of the 9 documents. I do not recall that I recognize the 10 first component of the documents. 11 Q. The computer listings? 12 A. That's correct. 13 Q. Okay. 14 A. I do recognize several of 15 these documents. 16 Q. The hit review sheets? 17 A. Yes, ma'am. 18 Q. What are the hit review 19 sheets, what's a hit review sheet? 20 A. As best I recall, these were 21 patients who had been in a Fluoxetine study where 22 the possibility of suicidal ideation or suicidal 23 activities could have occurred. 24 Q. Okay. Where were these Page 673 1 patients, from the United States trials or the 2 outside the United States trials? 3 A. These would appear to be from 4 outside the United States. 5 Q. How do you know that? 6 A. By the facility code. 7 Q. What does BP stand for? 8 A. I'm not sure. 9 Q. What are the U.S. facility 10 codes, what are the differences between the U.S. 11 facility codes and the OUS facility codes? 12 A. As I recall the U.S. would 13 have said U.S. I recognize some of these like 14 Canada, these might be from Britain, I'm not 15 sure. CA is Canada, EW was Erl Wood, which is 16 UK. 17 Q. Right. 18 A. To the best of my 19 recollection, FE is France, that may be 20 Basingstoke, I'm not sure. 21 Q. You mean BP? 22 A. Yes, ma'am. IT is Italy. 23 do you want me to go through all of these? 24 Q. No, that's okay. You don't Page 674 1 see any U.S. in there from your quick review, do 2 you? 3 A. I don't, no, not from my quick 4 review. 5 Q. Were hit review sheets filled 6 out for patients that were in the United States 7 clinical trials that suffered an adverse event 8 that might be related to suicidality? 9 A. I don't recall. 10 Q. Did you review clinical report 11 forms for patients in the United States trials 12 that were thought to have suffered a suicidality 13 related adverse event? 14 A. As I recall, I did. 15 Q. Do you recall filling out any 16 kind of form with regards to each of those 17 patients similar to the hit review sheets as part 18 of your review of those clinical report forms? 19 A. I don't recall. 20 Q. Who would know that, whether 21 or not hit review sheets or a similar form were 22 used in the review of the suicidality related 23 adverse events from the United States clinical 24 trials? Page 675 1 A. Doctor Beasley. 2 Q. When you reviewed the 3 suicidality related adverse events from the 4 clinical trials that were conducted outside the 5 U.S., what type of information did you have to 6 look at in your review, did you have the entire 7 clinical report form for each of those patients? 8 A. I don't recall. Do you want 9 me to try to refresh my memory by looking at the 10 whole package? 11 Q. Sure. 12 A. This doesn't help much. I 13 don't recall. 14 Q. If I told you that Catherine 15 Mesner and Laura Fludzinski testified that in 16 their depositions that as part of the OUS data 17 collection project that they were involved in, 18 they and other employees that went over to the 19 different affiliates outside the U.S. filled out 20 forms based on the clinical report forms and 21 flagged those that were related to suicidality 22 adverse events and sent the forms back, would 23 that refresh your recollection? 24 A. Those would be two very Page 676 1 accurate reporters so I would -- it doesn't 2 refresh my recollection. I do recall that there 3 were several people who made trips to review 4 documents, yes. 5 Q. Do you have any reason to 6 doubt their testimony to that effect that they 7 didn't send back the entire case report forms but 8 instead filled out forms, or work sheets I think 9 they called them, for all the patients that they -- 10 whose clinical report forms they reviewed? 11 MR. MYERS: Before he answers, let me 12 just object to the form, Nancy, to the extent I 13 don't know and I think you may not have 14 accurately, entirely captured the testimony of 15 those witnesses that I think you're trying to 16 recount. 17 MS. ZETTLER: The main point of this 18 is that they didn't send back all of the clinical 19 report forms for each of the patients in the 20 clinical trials, they went over there and 21 collected information from those forms. So I'm 22 trying to get a sense from Doctor Heiligenstein 23 if he looked at, as he testified he looked at 24 with regards to the violent aggressive behavior Page 677 1 adverse events, the entire clinical report form 2 grouping, I guess you could say, for each patient 3 throughout the clinical trial as part of the 4 suicidality review. 5 MR. MYERS: That's another question. 6 I was only objecting to the extent you're trying 7 to summarize exactly what they said and I don't 8 know if you got it a hundred percent right. I 9 understand what you're getting at. Do you 10 understand what she's trying to find out? 11 A. You asked in the context of -- 12 Q. Let me ask it this way, 13 because we don't have a whole lot of time left. 14 Did you review for those patients that were 15 thought to have suffered sometime during their 16 participation in a clinical trial, a suicidality 17 related adverse event, did you review that 18 patient's entire whole of clinical report forms 19 that were filled out during the clinical trial, 20 do you recall doing that for each patient? 21 22 MR. MYERS: U.S. or OUS? 23 MS. ZETTLER: OUS. 24 A. I do not recall doing that. Page 678 1 Q. How many patients to your 2 knowledge were flagged by the Lilly team that 3 went over to the OUS affiliates to review the 4 double-blind controlled studies were actually 5 flagged as suicidality related adverse events? 6 A. I do not recall how many 7 events were flagged. 8 Q. Would it surprise you if I 9 told you that Catherine Mesner said there were 10 hundreds? 11 MR. MYERS: Object to the form. Tell 12 her if you know. 13 A. Would I object? 14 Q. Would you be surprised if I 15 told you that Catherine Mesner said that there 16 were hundreds? 17 MR. MYERS: Same objection. If you 18 know, tell her. 19 A. I just don't know how many 20 there were. 21 Q. What's a hit? 22 A. That's a word that Doctor 23 Beasley used that as best I can recollect would 24 have been the identification of an event that may Page 679 1 or may not have some -- well, let me rephrase 2 that. It would have been some identified event 3 that may have some relationship to the 4 suicidality analysis. 5 Q. Okay. Do you recall outside 6 consultants reviewing the hits that were pulled 7 by the Lilly team that went to the OUS affiliates 8 to collect data on the clinical trials? 9 A. I do not recall outside 10 consultants, no. 11 Q. Do you recall what the 12 procedure was that the Lilly team that went to 13 the OUS affiliates to collect data went through 14 in reviewing the report forms? 15 A. I do not recall. 16 Q. And you don't recognize the 17 table listings that are a part of Exhibit 15, do 18 you, the listings of the MADRS questionnaire, 19 number ten, for example, you don't recognize 20 these? 21 A. No, ma'am. 22 Q. This first page of Exhibit 15 23 is entitled Physician Requirements, correct? 24 A. Yes, ma'am. Page 680 1 Q. And it's dated February 15, 2 1991? 3 A. Yes. 4 Q. And at the top it says OUS 5 suicide analysis definition, do you see that? 6 A. Yes, ma'am. 7 Q. Did you recognize that page? 8 A. I do not. 9 Q. Are you familiar with those 10 physician requirements that are listed there? 11 A. No, I do not. 12 Q. Okay. Do you recall any of 13 the procedures that you were to go through in 14 reviewing the hits? 15 A. I recall I have some 16 recollection of some procedures. 17 Q. Tell me what you remember. 18 A. When you say hits, you're 19 talking about OUS hits? 20 Q. Right. 21 A. As best I recollect, when that 22 information was gathered and returned or brought 23 to the United States, my role was to review, with 24 as I recall Doctor Beasley, those events or hits Page 681 1 as they were called. 2 Q. What were you looking for? 3 A. As best I recall, using a 4 definition that had been established, a priori, 5 we were looking for events or hits which 6 qualified for inclusion in the analysis. 7 Q. What's the definition? 8 A. I don't recall the specifics 9 of the definition. I do recall, a vague 10 recollection, it would be a patient who had 11 participated in a clinical trial and had been 12 taking Fluoxetine or a comparitor or a placebo, 13 as best I recollect, within a given time frame. 14 The event as I recall would have needed to occur 15 within a given time frame of the patient's 16 participation in the study. 17 Q. Were you blinded when you 18 reviewed the hits? 19 A. I believe I was, I don't 20 recall specifically though. 21 Q. Anything else you recall about 22 the definition? 23 A. No. 24 Q. Do you recall how an act was Page 682 1 defined? 2 A. I don't. 3 Q. How about an ideation? 4 A. I don't recall. 5 (PLAINTIFFS' EXHIBIT NO. 16 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 A. That's where these went. I 9 recognize this. 10 Q. Okay. Can you tell me what 11 that is, Exhibit 16, can you tell me what Exhibit 12 16 is? 13 A. Exhibit 16 are more or less a 14 phone log I kept of conversations that I had with 15 any of a number of people, mostly related to my 16 Lilly work, sometimes related to a repairman who 17 might be showing up at my house at a given time. 18 Just something I would keep a record of. 19 Q. Sometimes leasing for cars or 20 something like that? 21 A. Probably. 22 Q. You said that's where these 23 went. What did you mean? 24 A. I wanted to be sure that my Page 683 1 information had been turned over and I looked for 2 these to make absolutely sure and this confirms 3 that indeed I sent them in. 4 Q. Have you ever gotten the 5 originals back on those? 6 A. I haven't. 7 Q. Would you like to see the 8 originals? 9 A. I don't think I need to if 10 these are here. 11 Q. Did you ever tear pages out of 12 those books? 13 A. Probably did. 14 Q. For what reason? 15 A. Probably personal, leasing 16 arrangements, et cetera. 17 Q. What about work related phone 18 calls, would you have torn information related to 19 work-related phone calls out of the notebooks? 20 A. It's possible but unlikely. 21 Q. You turned those over to Lilly 22 legal, I take it? 23 A. Yes, ma'am. 24 Q. Have you seen copies of what Page 684 1 they've turned over to us? 2 A. I have not. 3 Q. Okay. Can you just take like 4 a few minutes to flip through there and see if 5 there's anything that jumps out at you that 6 you're missing? I know there's a lot of black 7 marks on there but they are dated so I don't know 8 if there's a specific event that sticks out in 9 your head that you may have made notes on that 10 are not there anymore. And, Doctor, I apologize, 11 they're not necessarily in chronological order by 12 notebook, I didn't put the notebooks in 13 chronological order. 14 A. You're asking me to do what? 15 Q. Like if there's a particular 16 date that you recall that your notes may be 17 missing or something like that. I want to make 18 sure that we get your impression on how accurate 19 that rendition of your notebook is. 20 A. It would appear to -- I can't 21 be confident of the thoroughness but it would 22 appear to be my notebooks. 23 Q. Okay. Would phone calls that 24 you have had with consultants be noted in there Page 685 1 possibly? 2 A. They may be. 3 Q. What other types of people, 4 just give me a general idea of the types of 5 people that you've spoken with that you would be 6 most likely to jot down notes about it in those 7 books, on your work side. I don't care about 8 your leasing or repairmen, things of that nature. 9 A. It would have been individuals 10 who called in adverse events or events that 11 occurred while individuals were taking 12 Fluoxetine, to report an event, to obtain 13 information. Many of those would have been 14 informational calls relative to can I use 15 Fluoxetine in this kind of a patient, some of it 16 would have been consultants that I was seeking to 17 engage to come in relative to Fluoxetine and 18 other compounds, other sort of informational 19 kinds of consultants. 20 Q. Okay. Clinical investigators, 21 phone calls from them? 22 A. Yes, could be, sure. 23 Q. People from the FDA who may 24 have contacted you? Page 686 1 A. Yes. 2 Q. People from the Rocky Mountain 3 Poison Control Center? 4 A. Possibly, yes. 5 (PLAINTIFFS' EXHIBIT NO. 17 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 A. I recognize those. 9 Q. Good, good. Can you tell me 10 what the documents are that comprise Exhibit 17? 11 A. These are daily printouts of 12 events occurring during clinical trials in which 13 I may have been a monitor or in the absence of a 14 colleague may have signed off on in his or her 15 absence. 16 Q. Did you make it a habit to 17 keep those in your files? 18 A. No. 19 Q. Because they were produced as 20 part of your file. 21 A. As part of my files? 22 Q. Yes, they were. 23 MR. MYERS: Just so the record is 24 clear, we also produced documents from other Page 687 1 person's files. 2 MS. ZETTLER: His name's not on there 3 anywhere. 4 MR. MYERS: I don't know about that. 5 Q. Your name's not on any of 6 those as far as you can see? 7 A. They are, I signed off on all 8 of these. 9 Q. Oh, I'm sorry, okay. So I see 10 when you say you signed off. 11 A. I can't imagine I would have 12 kept these, I signed them off and returned them 13 to the appropriate channels. 14 Q. Okay. But what they are are 15 printouts of daily adverse events that happened 16 either in your clinical trials that you had some 17 sort of responsibility over or clinical trials of 18 your colleagues if they happened to be 19 unavailable that day? 20 A. Correct. 21 Q. Now when you say you signed 22 off on those, what do you mean? 23 A. I reviewed each event and the 24 assignment of outcome and if there was further Page 688 1 information needed, I would flag the particular 2 event and either I or a research associate who 3 was the research associate of a particular 4 project would then follow up with the 5 investigative site. 6 MR. HARRIS: What time frame are those 7 for? 8 MS. ZETTLER: Let me ask him. 9 Q. Most of them -- can you give 10 me a general idea of when those were produced? 11 A. 1986-1987. 12 Q. Have you done that fairly 13 consistently with Fluoxetine throughout the time 14 that you worked at Lilly on Fluoxetine, are you 15 still reviewing daily printouts? 16 A. I still review daily printouts 17 but they're not from studies of Fluoxetine unless 18 my colleagues are absent and someone is needed to 19 sign off in their absence. 20 Q. When is the last time you 21 recall reviewing a daily printout on Fluoxetine? 22 A. I do have one study in which 23 Fluoxetine is a comparitor and that study on a 24 daily basis or whenever they're delivered to me, Page 689 1 I do sign off on. So I do that. I've done it 2 with studies involving Fluoxetine to the present. 3 Q. Okay. Did you do that when 4 you first started working at Lilly back in 1986? 5 A. Sign off on these reports? 6 Q. Right. 7 A. Yes, ma'am. 8 Q. And you did it throughout the 9 first period of time that you worked at Lilly? 10 A. Yes, ma'am. 11 Q. And then you did it when you 12 came back to Lilly in '88 I believe it was? 13 A. That's correct. 14 Q. And you've done it from '88 to 15 the present? 16 A. Yes, ma'am. 17 Q. And do you do the same thing 18 with all of the sign offs, the sheets you sign 19 off on, you return them to the same place? 20 A. I returned them to the 21 research associate. 22 Q. The CRA? 23 A. Who was responsible for the 24 study at their level. Page 690 1 Q. Do you know -- is there any 2 reason that you know of why we would have gotten 3 the daily sign off sheets for that time frame, I 4 think you said it was '87-88, but not from before 5 or after? 6 A. I have no idea. 7 Q. Okay. 8 MR. MYERS: Actually he said these 9 were '86 to '87. 10 MS. ZETTLER: I'm sorry '86 to '87. 11 Q. Did there come a time when an 12 event would be considered expected only when it 13 was listed in both the clinical investigation 14 brochure and the package insert, to your 15 knowledge? 16 A. I don't recall. 17 (PLAINTIFFS' EXHIBIT NO. 18 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 A. Okay. 21 Q. Have you had a chance to 22 review Exhibit 18? 23 A. Yes, ma'am. 24 Q. Do you recognize that exhibit? Page 691 1 A. Yes, ma'am. 2 Q. Can you tell me what the 3 subject matter of that exhibit is? 4 A. It's the standardizing 5 expectancy of post-marketing trial, ADR. 6 Q. Okay. Does this relate to 7 Fluoxetine? 8 A. It would relate to Fluoxetine. 9 Q. It's an E-mail dated January 10 29, 1993 authored by Phyllis Donahue, correct? 11 A. Yes, ma'am. 12 Q. What is Phyllis talking about 13 there when she says in an effort to maintain 14 consistency when assessing adverse drug 15 experience reports obtained from post-marketing 16 studies regulatory management with counsel from 17 the legal division has decided that an event must 18 be listed in both the clinical investigation 19 brochure and the package insert to be considered 20 expected. 21 MR. MYERS: Let me just ask maybe 22 before I object, you want to know what he 23 understands, not what she was -- 24 MS. ZETTLER: Right. Page 692 1 MR. MYERS: Okay. 2 A. As I understand it, if one is 3 a monitor for a post-marketing study with any 4 compound, that one should ascertain if the event 5 is serious. If the event is serious one should 6 ascertain that the event is expected according to 7 the information provided in both the CIB and the 8 package insert. 9 Q. So am I correct in saying that 10 if, for instance, suicidality is listed in the 11 package insert but if it is not listed in the 12 CIB, then it's considered unexpected? 13 MR. MYERS: Let me just object to the 14 form. At what point in time, since the date's 15 been -- 16 MS. ZETTLER: The time of this memo or 17 shortly thereafter. 18 A. Could I have the question read 19 back? 20 (THE COURT REPORTER READ BACK THE 21 REQUESTED TESTIMONY.) 22 A. An event involving suicidality 23 that would be un -- it would be serious. 24 Q. Right, I'm just talking Page 693 1 expectancy because that's all this is talking 2 about. 3 MR. MYERS: You want to know about any 4 event? 5 MS. ZETTLER: Right, I'm just using 6 suicidality as an example. 7 A. Yes, it would need to. 8 Q. Be both in the CIB, correct? 9 A. That's right. 10 Q. As well as the package insert? 11 A. Yes, ma'am. 12 Q. As far as you know is that 13 okay with the FDA, regulatory-wise? 14 A. I don't know. 15 Q. Do you have a problem with 16 that, determining expectancy on the basis of both 17 what is contained in the package insert as well 18 as the CIB? 19 A. No. 20 Q. Why not? 21 A. Well, as much as possible, we 22 tried to keep the CIB current in a compound 23 that's been marketed with the post-marketing 24 experience. So when the package insert would be Page 694 1 updated, then the CIB would be updated to the 2 best of my knowledge. 3 Q. Okay. Let's go back to 4 Exhibit 12. Doctor, do you know why the package 5 insert for Fluctin in Germany is different than 6 the package insert here in the United States with 7 regards to that one section that Paul was talking 8 about earlier, the risk of suicide patients? 9 MR. MYERS: Let me object to the form 10 to the extent that package inserts are governed 11 by regulatory law and regulations. 12 MS. ZETTLER: I object to your giving 13 him hints on how to answer the question. 14 MR. MYERS: I'm not giving him a hint. 15 I object to the form of the question because, 16 before you interrupted me, that may call for him 17 to make some sort of legal conclusion under 18 either the law and regulations in Germany or the 19 federal regulations. 20 MS. ZETTLER: I'm not asking him for a 21 legal conclusion, I'm not asking him for a 22 regulatory conclusion. I'm asking him if he 23 knows why there's a difference. 24 Q. Do you want to read back the Page 695 1 question? 2 A. Please. 3 (THE COURT REPORTER READ BACK THE 4 REQUESTED TESTIMONY.) 5 MR. MYERS: Same objection. If you 6 know, tell her. 7 A. In a definite way that I could 8 say yes or no why I understand why they're 9 different, no, I don't have a full understanding. 10 Q. Okay. Do you have an opinion 11 why they're different? 12 A. Yes. 13 Q. What is your opinion? 14 A. My opinion would be that the 15 regulatory agencies for those countries would 16 require different language in the package insert. 17 Q. Okay. To your knowledge, has 18 the German government seen any information with 19 regards to the safety or efficacy of Fluoxetine 20 that the FDA has not seen? 21 A. Not to my knowledge. 22 Q. Do you know of any prohibition 23 within the FDA regulations against Lilly placing 24 language similar or identical to what is listed Page 696 1 in the Fluctin packaging with regards to the risk 2 of suicide patients in the United States package 3 insert? 4 MR. MYERS: Same objection. If you 5 know, tell her. 6 A. I'm not aware. 7 Q. You're not aware of any 8 prohibition? 9 A. Promotional materials would be 10 required to be consistent with one's package 11 labeling. If they're not, a division within the 12 FDA can ask that that material be pulled so that 13 in situations where we're developing promotional 14 materials specifically for the United States, we 15 would make it consistent with our package 16 labeling. 17 Q. But the promotional material 18 does not dictate what goes into the package 19 insert, does it? It's the other way around, 20 isn't it? 21 A. No, the package labeling will 22 oftentimes determine the language that one can 23 use in their promotional materials. 24 Q. Have you ever been aware of a Page 697 1 situation where the FDA has criticized Lilly's 2 promotional material in any way on Prozac? 3 A. I have a vague recollection. 4 Q. A vague recollection of 5 criticism? 6 A. That there was some criticism. 7 Q. Do you recall what the subject 8 matter of that criticism was? 9 A. No, I do not. 10 Q. Were you involved in 11 responding to any FDA inquiries regarding any 12 package insert or any promotional material that 13 they were criticizing? 14 A. Is that your question? That's 15 two questions. 16 Q. I threw in package insert 17 there and I didn't mean to. Any promotional 18 material, do you recall being involved in any 19 criticism the FDA had of any promotional material 20 that Lilly was using with regards to Fluoxetine? 21 A. I do not recall being 22 involved. 23 Q. I think it was when I asked 24 you if you know of any prohibition to Lilly Page 698 1 adding language that they're using in the Fluctin 2 package insert, you pointed to an apparent 3 problem with the promotional materials, changing 4 the package insert because of the promotional 5 material has been used, is that what you're 6 saying? 7 A. I may not remember your 8 original question correctly because I thought the 9 original question was using the language of the 10 German package labeling in the United States 11 promotional materials, as I understood your 12 original question. 13 Q. Either I misspoke or you 14 misunderstood me. I just want to understand, you 15 know of no prohibition under the FDA regulations 16 prohibiting Lilly from placing the language they 17 used in the Fluctin package insert into the 18 United States package insert with regards to this 19 section on patients who are risk of suicide, 20 correct? 21 MR. MYERS: I object to the form, that 22 requires some sort of a legal conclusion. 23 MS. ZETTLER: I'm asking him if he 24 knew of any. Page 699 1 MR. MYERS: I still object. If you 2 know, tell her. 3 A. There might be, given that the 4 FDA reviews all package labeling changes and so 5 one could just not say to the FDA put this in, 6 because they may say we don't want it in. 7 Q. Why? 8 A. I don't work for the FDA, I 9 don't know. 10 Q. Do you think that the FDA 11 would tell Lilly not to place something in the 12 Prozac package insert that Lilly uncovered with 13 regards to the safety of Fluoxetine? 14 MR. MYERS: Same objection and that 15 would be speculative as to what the FDA would do 16 or might do. 17 Q. Do you understand my question? 18 A. Could you repeat it? 19 Q. What if all of a sudden -- 20 MS. ZETTLER: And I'm using this as 21 example, Larry, so don't freak out, okay. 22 Q. What if all of a sudden Lilly 23 found that Prozac caused seizures, okay. And 24 they went to the FDA and they said we have Page 700 1 uncovered evidence in our clinical trials or 2 through some other means that indicates that 3 Prozac may cause seizures in some depressed 4 patients, we'd like to change the package label 5 to reflect that information. Can you conceive of 6 any situation where the FDA would say no, no, 7 Lilly, please don't do that, we don't think it's 8 appropriate? 9 MR. MYERS: Same objection. If you 10 know, tell her. 11 A. What I can tell you is that in 12 our surveillance when we discovered an event that 13 we felt bore a relationship to Fluoxetine, in 14 some instances where those events had been 15 reported then we did approach the FDA and there 16 was no objection from the FDA. 17 Q. To putting that in the package 18 insert? 19 A. That's correct. 20 Q. Okay. Now answer my question. 21 Can you conceive of any situation where if Lilly 22 came to the FDA with information that indicated 23 that Prozac -- a change in Prozac safety profile, 24 for instance, where they would prohibit Lilly Page 701 1 from changing that if it was a negative impact on 2 the drug? 3 MR. MYERS: Same objection as to the 4 form and the term negative impact on the drug. 5 Q. Or negative impact on the 6 patient, I guess is better. 7 A. I have not been a consistent 8 interactor with the FDA regarding those types of 9 changes. My sense is that they have always been 10 responsive and willing to engage in a dialogue 11 relative to those kinds of matters. 12 Q. What does it mean for a drug 13 to be activating? 14 A. My interpretation of that is 15 an individual may feel some increased energy. 16 Q. What does it mean for a drug 17 to be sedating? 18 A. It suggests to me that a 19 patient may feel somewhat more drowsy or 20 lethargic. 21 Q. Is Fluoxetine a sedating drug? 22 A. There have been reports of 23 patients who feel very tired on the medication. 24 Q. Could that be a result of Page 702 1 insomnia that they're suffering from? 2 A. No. 3 Q. Why not? 4 A. Because those reports did not 5 include the patient's complaint of insomnia. 6 Q. Is Fluoxetine an activating 7 drug? 8 A. How do you define activating 9 in that sense? 10 Q. We'll use your definition. 11 A. In some patients, it appears 12 that some patients become a bit more energetic, 13 yes. 14 Q. Can activation by a drug have 15 a negative impact on a patient? 16 MR. MYERS: I'm going to object to the 17 form and the term "negative impact" as being a 18 little bit vague, maybe over broad too. If you 19 know, tell her. 20 A. In my estimation that would be 21 unlikely. 22 Q. Why? 23 A. Not entirely possible. 24 Q. Why? Page 703 1 A. Are you speaking specifically 2 of Fluoxetine or just -- 3 Q. Start generally. 4 A. I think it depends upon the 5 medication and the level of increased energy that 6 person feels, so that there are some medications, 7 some substances that might as a component of its 8 effects, and a significant targeted component of 9 its effect, have some activation. There are 10 other medications in which there may be a quality 11 of increased energy in a subset of patients which 12 would not necessarily be detrimental, in fact may 13 be a very positive attribute of the medication. 14 (PLAINTIFFS' EXHIBIT NO. 19 WAS 15 MARKED FOR IDENTIFICATION AND 16 RECEIVED IN EVIDENCE.) 17 A. Okay. 18 Q. Have you had a chance to 19 review Exhibit 19? 20 A. Yes, I have. 21 Q. Do you recognize this exhibit, 22 Doctor? 23 A. Yes, I do. 24 Q. Tell me what it is. Page 704 1 A. It's a communication from 2 Doctor Beasley to a group of individuals in which 3 he summarizes some analyses that he did regarding 4 activation and sedation in a trial of Fluoxetine, 5 Imipramine and placebo. 6 Q. Do you know why Doctor Beasley 7 went through this exercise? 8 A. I believe in response to 9 questions about the nature of Fluoxetine's 10 activating qualities as compared to other more 11 standard types of compounds and placebo. 12 Q. Questions by whom? 13 A. Prescribers, as best I would 14 recollect. 15 Q. This is dated October 20, 16 1989, correct? 17 A. Yes, ma'am. 18 Q. To your knowledge, did the 19 issue of whether or not Fluoxetine was activating 20 or sedating ever arise prior to this? 21 A. To this particular date? 22 Q. To this particular project. 23 A. I believe it had been raised. 24 Q. Okay. In the second page of Page 705 1 the exhibit, Doctor Beasley poses three questions 2 and then at lists his answer to each of those 3 questions, correct? 4 A. Correct. 5 Q. The first question is: Is 6 Fluoxetine independent of baseline psychomotor 7 status activating, sedating or neither compared 8 to Imipramine or placebo, correct? 9 A. That's correct. 10 Q. He states that in response to 11 that question, it is both more activating and 12 more sedating than placebo and is more activating 13 than Imipramine, does he not? 14 A. That's correct. 15 Q. Were you surprised by that? 16 A. I am a bit surprised by the 17 comparison with Imipramine. 18 Q. Yes? 19 A. Because I would have 20 thought -- well, I would have thought based upon 21 my own work in a group of patients who were 22 baseline agitated that Imipramine might have been 23 more troublesome than it appeared to be in this 24 study. Page 706 1 Q. So they would have been 2 equally activating, is that what you're saying? 3 A. That would have been possible, 4 I suppose, when one considers the spectrum of 5 activity of Imipramine including its 6 anticholinergic sedative properties or, you know, 7 sedating properties that it probably would have 8 been somewhat less activating as I read through 9 this and think through it. 10 Q. And Doctor Beasley also found 11 that there was a trend for agitated patients to 12 experience more activation with Fluoxetine, 13 correct? 14 MR. MYERS: Are you reading that from 15 somewhere? 16 MS. ZETTLER: The second one. 17 MR. MYERS: Okay, number two. 18 A. That's correct. 19 Q. Does that comport with what 20 your findings from your agitated depressed study? 21 A. No. 22 Q. How do you explain the 23 difference between what Doctor Beasley found in 24 the multi-center Fluoxetine, Imipramine, placebo Page 707 1 trial and your agitated depressed study? 2 A. As best I recollect, Doctor 3 Beasley in this analysis, the study was not 4 intended to look at that particular question and 5 his analysis as I recall he used events that 6 occurred during the trial which he lumped 7 together as activating events and sedating events 8 and then applied those to the data base. In the 9 study that was designed specifically to look at 10 patients who are baseline agitated and depressed, 11 to enter the study the patient must have had -- 12 met the RDC criteria for agitation and we used 13 the RDC criteria in a scale form to score the 14 patient's levels of activation over the course of 15 the study -- their levels of agitation over the 16 course of the study. 17 Q. You're talking about the scale 18 that Lilly developed, correct? 19 A. That's correct. 20 Q. The one you talked about 21 yesterday that wasn't validated, correct? 22 A. That particular scale was not 23 validated but to the best of my knowledge the RDC 24 criteria had been validated. Page 708 1 Q. I'm talking specifically about 2 the scale, Doctor. You used the scale in your 3 study that was developed by Lilly that was never 4 validated, correct? 5 A. That's correct. 6 Q. Is it true what Doctor Beasley 7 says in the second paragraph on page one that 8 assessing patients' baseline psychomotor activity 9 level is itself a complex issue? 10 A. I don't know what he was 11 saying specifically. 12 Q. Were you trying to assess a 13 patient's baseline psychomotor activity level 14 with the scale that Lilly developed with regards 15 to agitation in your study? 16 A. No, I don't think that's what 17 he's referring to because later in this 18 communication, he does state in the third 19 sentence of the second paragraph, the SADS and 20 RDC criteria, and he is in this sentence 21 referring to those RDC criteria for psychomotor 22 retardation and agitation provide operational 23 criteria for assigning patients categorically, or 24 global judgments may be made. Unfortunately, Page 709 1 there are no severity rating instruments 2 specifically for psychomotor activity. Then he 3 goes on. And then in the second sentence of the 4 third paragraph, he says although this could have 5 been improved upon by using the SADS questions 6 and RDC criteria, the global assessment is 7 identical to routine clinical practice. What I 8 think I hear him saying here is that had he had 9 the opportunity to design such a study, he would 10 have used those RDC and SADS criteria as a way of 11 better assessing baseline sedation and 12 activation. 13 Q. Let me try my question again. 14 With the questionnaire that you developed to use 15 in the agitation study, the one that was never 16 validated, okay, were you trying to assess the 17 patient's baseline psychomotor activity level? 18 A. We -- that specific scale 19 addresses the patient's level of agitation. 20 Q. So the answer is yes? 21 A. To some extent, psychomotor 22 activity would be, you know, as a component of 23 agitation. 24 Q. What are the other components Page 710 1 of agitation? 2 A. As I recall, there are 3 observational information in addition to the 4 individual's reports of psychomotor activity. 5 Q. Such as? 6 A. Again, as best I recollect, 7 there I believe is a question asking the 8 clinician to score the patient on his or her 9 observation of the patient's level of agitation 10 and there are additional questions relative to 11 specific aspects of agitation such as hand 12 wringing, restlessness, pacing, that sort of 13 thing. 14 Q. Is it anything to do with the 15 psychological assessment or is it only like a 16 physical psychomotor assessment? 17 A. I vaguely recall that there is 18 a question that has to do with some psychological 19 component but I cannot be certain of that. 20 Q. Anything built in to judge a 21 person's hostility level? 22 A. Not in that question, no. 23 Q. Is Prozac a stimulating drug? 24 A. Can you define stimulating? Page 711 1 Q. As opposed to a sedating. 2 A. I think I would not use the 3 world stimulating as much as I would use 4 energizing and I would say it is more energizing 5 than it is sedating. 6 Q. Does it have stimulant 7 properties? 8 A. No, it does not. 9 Q. Isn't it true that there have 10 been reports of false-positive tests for 11 amphetamines with people using Prozac? 12 A. I recall that there were 13 reports that patients had tested positive for 14 amphetamine and they claimed that they had not 15 used amphetamines and that those patients were 16 being treated with Fluoxetine. 17 Q. So you're saying that the 18 patients were lying about whether or not they 19 were using amphetamines? 20 A. No. A false-positive means 21 just what it is, it's a false-positive. It could 22 be a matter of standardization, it could be an 23 error in the laboratory. There are 24 false-positives with all screening tests for Page 712 1 substances in the urine and false-negatives. 2 Q. Is it possible that somebody 3 could test positive for amphetamines when taking 4 Prozac and no amphetamines? 5 A. I don't believe that's 6 possible. 7 Q. So it's laboratory error 8 that's to blame? 9 A. I would suggest that would be 10 one possibility. 11 (PLAINTIFFS' EXHIBIT NO. 20 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 A. Do you want me to review the 15 entire document? 16 Q. Yes, glance through it. You 17 don't have to read it word for word. 18 A. Okay. I have reviewed the 19 document. 20 Q. Pardon? 21 A. I reviewed the document. 22 Q. Do you recognize this exhibit, 23 Doctor? 24 A. I have some vague recollection Page 713 1 of the document, yes. 2 Q. Tell me what it is to the best 3 of your recollection. 4 A. It appears to be a 5 communication or is a communication from Mary 6 Sayler to Doctor Beasley in which she carbon 7 copies two additional statisticians as regards 8 the analysis that Doctor Beasley shepherded 9 reviewing the activating or sedating test events, 10 Fluoxetine versus Imipramine versus placebo. 11 Q. On the first page of -- the 12 second page of the exhibit, the first page of the 13 actual substantive text, she lists specific 14 events of interest in towards the middle of the 15 page. Do you see that? 16 A. Yes, ma'am. 17 Q. She says activating events are 18 nervousness, anxiety, agitation and insomnia. Do 19 you see that? 20 A. Yes, ma'am. 21 Q. And sedating events are 22 somnolence and asthenia? 23 A. Yes, ma'am. 24 Q. Is it your testimony, Doctor, Page 714 1 that if somebody is suffering from an activating 2 adverse event such as nervousness, anxiety, 3 agitation or insomnia that that doesn't have a 4 negative impact on them? 5 A. I would not necessarily agree, 6 and I know that there are many people that did 7 not agree with Doctor Beasley's classification of 8 such events, so I would say that if someone is 9 experiencing some nervousness, anxiety, 10 agitation, insomnia, somnolence or asthenia, one 11 doesn't know for sure if that's necessarily 12 caused by a drug or a placebo, that may not be 13 part of the patient's current situation, the 14 illness or some stress the individual is 15 experiencing, and I would say that it certainly 16 is that if someone who's experiencing that might 17 certainly experience some level of discomfort and 18 impairment of their sense of well-being, in some 19 instances but not all. So that many of us 20 function on a day do day basis feeling some 21 nervousness and we might like to feel better but 22 it doesn't significantly impair the quality of 23 our work. 24 Q. Why does Doctor Beasley pick Page 715 1 these adverse events as activating? 2 A. You would have to ask Doctor 3 Beasley. 4 Q. Have you ever discussed this 5 with him? 6 A. We had some discussion. 7 Q. Did he explain to you why he 8 picked those as activating adverse events? 9 A. Yes. 10 Q. What did he say? 11 A. As best I recall, these are 12 events that he felt were activating events. 13 Q. Did he say why he thought they 14 were activating events? 15 A. No. He just said -- Charles 16 can be dogmatic, and so he does that, he does 17 that -- 18 (WITNESS HITS TABLE WITH HAND) 19 A. And he's going to do what it 20 is he thinks he needs to do. 21 Q. So he's stubborn, is that what 22 you're saying? 23 A. I think he's stubborn. 24 Q. Has he ever been talked out of Page 716 1 listing these events as activating events, to 2 your knowledge? 3 A. Not that I'm aware of, he did 4 a thorough, I mean a very extensive and 5 exhaustive analysis. 6 Q. Is it your opinion that 7 Fluoxetine can never cause the activating events 8 of nervousness, anxiety, agitation or insomnia? 9 A. No, that's not my opinion. 10 Q. So it can cause those adverse 11 events? 12 A. I think there are events that 13 have occurred that would likely be related to the 14 prescribing of Fluoxetine. 15 Q. Do you know who the 16 investigator that was dropped from all the 17 analyses that Doctor Beasley talks about at the 18 top of the page there was? 19 A. No. 20 MS. ZETTLER: It's a pivotal trial, 21 Larry. 22 A. I don't know. 23 Q. Is it Doctor Kohn? 24 A. I'm not sure, it may have Page 717 1 been. 2 Q. Okay. Are you aware that 3 there was a problem with Doctor Kohn's trial that 4 he did that was included in the multi-center 5 study, that his analysis was dropped from the 6 efficacy -- or his study results were dropped 7 from the efficacy portion of the analysis? 8 A. I have some vague recollection 9 of that. 10 Q. What is a VAMP data base? 11 A. I don't recall, I don't 12 recall. 13 (PLAINTIFFS' EXHIBIT NO. 21 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 Q. Have you had a chance to 17 review Exhibit 21? 18 A. I have. 19 Q. Do you recognize the exhibit? 20 A. I have a vague recollection, 21 yes. 22 Q. Can you tell me what you 23 remember? 24 A. As I recall there, was a data Page 718 1 base with the acronym of VAMP, which I don't know 2 what that means, that was given some 3 consideration relative to looking at specific 4 issues, most likely suicidality given the text of 5 the message and most likely an epidemiological 6 study. 7 Q. Is this a Lilly data base? 8 A. It is not. 9 Q. Do you know whose data base it 10 is? 11 A. I don't. 12 Q. Why is it that a study of 13 suicidality wasn't done using the data base? 14 A. I believe that Doctor Kotsanos 15 reviewed this particular data base and reached 16 the conclusion it would not be an appropriate 17 data base to use. 18 Q. Why? 19 A. I don't know. 20 (PLAINTIFFS' EXHIBIT NO. 22 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 MS. ZETTLER: Just to make it clear, 24 the exhibit regarding the VAMP data base is Page 719 1 Exhibit Number 21. 2 MR. MYERS: Right. 3 MS. ZETTLER: And the exhibit 4 regarding Doctor Beasley's analysis of activating 5 and sedating test results where he lists the 6 activating events of nervousness, anxiety, 7 agitation and insomnia is Exhibit 20. 8 MR. MYERS: Yes. 9 A. Okay. I reviewed the 10 document. 11 Q. Do you recognize this 12 document, Doctor? 13 A. I do not. 14 Q. It purports to be a memo or 15 E-mail dated June 26, 1984, correct? 16 A. That's correct. 17 Q. And it's written by a 18 J. Schenk and H. J. Weber, correct? 19 A. That's correct. 20 Q. Do you have any idea why this 21 would have been included in your documents? 22 MR. MYERS: Let me object to the form 23 because I don't think it was, Nancy, because just 24 from the legend that's on them, this is a Page 720 1 Fentress legend and his document had the MDL. 2 MS. ZETTLER: I know but there was one 3 included in his. 4 MR. MYERS: Well, he didn't even work 5 there then. 6 MS. ZETTLER: I know but that issue 7 has come up numerous times over the years. 8 A. I don't recall that this 9 document was in my files. 10 Q. Okay. Are you aware that 11 these issues have been raised by the German 12 government at various times since 1984 with 13 regards to Fluoxetine? 14 A. I'm aware of some of these 15 issues. 16 Q. Which issues? 17 A. I'm aware of the questions 18 regarding phospholipidosis. 19 Q. Okay. 20 A. And I was aware that the BGA 21 had requested additional information relative to 22 suicide and suicide attempts. 23 Q. Point number what? 24 A. Fourteen. Page 721 1 Q. Okay. Let's look at that one. 2 A. Okay. 3 Q. This exhibit says, As we 4 already explained by our Telex to Doctor Zerbe on 5 June 8, '84 we need a careful analysis of 6 suicides and suicide attempts. Correct? 7 A. Correct. 8 Q. It goes on to say, Patient by 9 patient, comma, symptomatology, comma or slash, 10 severity upon entry into the study and week by 11 week until the event occurred, comma, dose of 12 Fluoxetine, comma, side effects, comma, et 13 cetera. Correct? 14 A. That's correct. 15 Q. This is a very serious issue 16 in the opinion of the BGA, it might well be that 17 we will have to recommend concomitant 18 tranquilizer intake for the first two or three 19 weeks in the package literature. Correct? 20 A. That's correct. 21 Q. In fact that's what happened, 22 is it not, a recommendation that concomitant 23 sedatives be used in serious suicidal risk 24 patients is in fact in the current package insert Page 722 1 in Germany, is it not? 2 A. There is some language I would 3 need to review in the package labeling. 4 (COUNSEL HANDS DOCUMENT TO WITNESS.) 5 MR. MYERS: And while he's looking, 6 let me just object to the form of the question 7 because I really don't understand whose 8 recommendation you're asking him about. Are you 9 asking him is the recommendation that's suggested 10 in the memo what's in the insert or is there a 11 recommendation in the insert? 12 MS. ZETTLER: I think the questions 13 are pretty clear, Larry. 14 MR. MYERS: I object to the form then 15 because it's not, at least it's not clear to me. 16 MS. ZETTLER: Well, it's late. 17 MR. MYERS: Not that late. 18 A. In the discussion of the 19 Fluctin package labeling, under risk of suicide, 20 they do make a statement that therefore for his 21 or her own safety, the patient must be 22 sufficiently observed until the antidepressant 23 effect of Fluctin sets in, taking an additional 24 sedative may be necessary, this also applies in Page 723 1 cases of extreme sleep disturbances or 2 excitability. As I read that, I read the 3 communication which was what whoever Schenk is 4 and Doctor Weber heard, the language became more 5 specific in the package labeling. 6 Q. But in effect recommends the 7 use of a sedative in serious suicidal risk 8 patients, correct? It doesn't require it but it 9 recommends it in some cases at least. 10 A. What it says, it may be 11 necessary. 12 Q. So in some cases it recommends 13 that you should use a sedative? 14 A. It says if the physician or 15 whoever the prescriber is may find it necessary 16 to concomitantly prescribe a sedative. 17 Q. In serious risk of suicide 18 patients? 19 A. That would be the case as I 20 read that. 21 Q. Okay. So is it fair to say 22 that the package insert recommends in at least 23 some cases of patients who are at risk for 24 suicide that concomitant sedative be used at Page 724 1 least until the onset of the action of 2 Fluoxetine? 3 A. It doesn't say until the onset -- 4 it does not say until the onset of activity 5 occurs, it says that it just may be necessary. 6 Q. Okay. So at any given time 7 during therapy with Fluoxetine? 8 A. I think they're speaking early 9 in the course of treatment with a patient who 10 presents with serious risk of harming themselves. 11 Q. So in those parameters, it's 12 fair to say they're recommending the use of a 13 concomitant sedative at least in some patients 14 who present a risk of suicide? 15 A. They say it may be necessary, 16 yes. 17 Q. Does that clarify why that's 18 in the Fluctin package insert looking at the 19 concerns that they raised in 1984? 20 MR. MYERS: I'm going to object to the 21 question only because, Nancy, you all have asked 22 him a lot of questions about documents but he 23 didn't even work for Lilly in 1984, so, you know. 24 Q. Do you have any reason to Page 725 1 believe, Doctor, that the BGA did not raise this 2 issue? 3 MS. ZETTLER: In fact I think he 4 testified that he was aware that they did raise 5 the issue, Larry. 6 MR. MYERS: That's a different 7 question. Let's see what the pending question 8 is. 9 (THE COURT REPORTER READ BACK THE 10 PREVIOUS TWO QUESTIONS.) 11 Q. Do you understand what my 12 question is? 13 A. That helps me understand that 14 the concern was there in 1984. Not being privy 15 to any of those discussions, I cannot say that's 16 definitively linked to that but there would 17 appear to be some linkage. 18 Q. Do you have any reason to 19 believe that the reason that the BGA lists their 20 recommendation that at least in some patients who 21 present a suicide risk a sedative also be given 22 is because of prescribing methods in Germany as 23 opposed to the BGA's concern about the risk of 24 suicidality and the use of Fluoxetine? Page 726 1 A. Not having been involved in 2 those discussions or in discussions with other 3 compounds that may have been registered in 4 Germany at any point in time, that would be used 5 in the treatment of patients with depression, I 6 can't be sure that it does not reflect more to 7 prescribing practices in Germany than a specific 8 concern. I wouldn't be able to make that 9 distinction in a clear cut fashion. 10 Q. Are you familiar with the 11 prescribing practices of psychiatrists in 12 Germany? 13 A. I'm somewhat familiar with the 14 European psychiatrists and specifically the 15 Germans as well. 16 Q. Where do you get your 17 information that they're more apt to prescribe a 18 sedative along with the antidepressant in the 19 treatment of depression? 20 A. From some of the international 21 meetings, from networking with my colleagues at 22 Lilly who have responsibility for European 23 protocols and when the issue of exclusion 24 criteria are addressed, the response of the Page 727 1 opinion leaders in Europe is that it's a standard 2 in these countries, you cannot tell us we can't 3 use it because that's just the way we treat 4 patients. 5 Q. Concomitant sedatives? 6 A. Yes. 7 Q. Look at point number ten. It 8 says another question raised by the BGA was the 9 comparative use of concomitantly taking hypnotics 10 and benzodiazapines in agitated, slash, retarded 11 Fluoxetine patients versus agitated, slash, 12 retarded patients on comparitors. Do you see 13 that? 14 A. Yes, ma'am. 15 Q. The reason, and it says, 16 quote, reason colon, the BGA suspects Fluoxetine 17 to be a stimulating, slash, activating drug, 18 paren, side effects profile, 19 comma, suicides, comma, suicide attempt, close 20 paren, period. Correct? 21 A. Right. 22 Q. Does that indicate to you why 23 they wanted to recommend the use of a concomitant 24 sedative in serious suicidal risk patients? Page 728 1 MR. MYERS: Let me object again 2 because as I said before since he didn't work 3 there at the time, it would be highly speculative 4 for him to make that kind of an assessment 5 because he didn't have any knowledge because he 6 wasn't there at the time. 7 MS. ZETTLER: He's also given us quite 8 a few opinions on why it would be appearing in 9 the package insert. 10 MR. MYERS: I don't know that I would 11 agree with that. If you know, Doctor, tell her. 12 A. This is again a communication 13 not from the BGA but from Lilly personnel in 14 Germany as they reported concerns. I just would 15 not have been a part of that process and I 16 wouldn't have any of the details or had the 17 opportunity to interact directly with those 18 authorities to clarify any questions that I might 19 have and I think you're asking of me. So I 20 wouldn't know. 21 Q. Do you know of any 22 psychiatrists who are prescribing Fluoxetine and 23 a concomitant sedative or a drug with a sedative 24 property to it here in the United States? Page 729 1 A. Routinely? 2 Q. Yes. 3 A. I'm not aware of any 4 psychiatrists doing that on a routine basis. 5 Q. How about Doctor David Dunner, 6 are you aware that he testified in his deposition 7 that he's given up to fifty percent of his 8 patients on Fluoxetine a concomitant sedative or 9 a tricyclic or other antidepressant with a 10 sedative effect? 11 MR. MYERS: Before he answers the 12 question, let me object to the form to the extent 13 you're trying to capture Doctor Dunner's 14 testimony. I don't think that's accurate or 15 precise. 16 MS. ZETTLER: It's absolutely accurate 17 and precise. 18 Q. Did you know that, Doctor? 19 A. I'm not aware of that. 20 Q. Would that surprise you? 21 A. At one level it surprises me. 22 At another level it doesn't necessarily given 23 Doctor Dunner's role as a tertiary care 24 psychiatrist. He would see a lot of difficult to Page 730 1 treat patients who might have had difficulty with 2 other antidepressants or been unresponsive prior 3 to prescribing Fluoxetine, so he may have a 4 strategy that he engages in with those patients. 5 Q. Doctor Dunner's testimony, 6 Doctor, is that he felt it necessary at times to 7 prescribe concomitent sedatives or tricyclic or 8 other antidepressants with a sedative effect or 9 sedative properties to them to patients who are 10 on Fluoxetine, not the other way around. 11 A. Uh-huh. 12 Q. Why do you say it surprises 13 you? 14 MR. MYERS: Same objection as to 15 Doctor Dunner's testimony. And I think he 16 answered that. 17 MS. ZETTLER: He said in one respect 18 it surprises him and in another respect it 19 doesn't. He told us why it doesn't surprise him 20 in one respect and I want to know why it 21 surprises him on the other hand. 22 A. Speaking from my own 23 experience, it seems a bit aggressive. 24 Q. You said you were aware that Page 731 1 the BGA had raised the issue of suicide and 2 suicide attempts, tell me how you became aware of 3 that. 4 A. I recall when I first came to 5 Lilly, that Doctor Wernicke was working on that 6 issue to some extent among other projects that he 7 had responsibilities for. 8 Q. Did you work with him on that 9 issue at all? 10 A. I may have helped him 11 construct some sort of line listing, I don't 12 recall specifically. I would not have had a more 13 active role, if that. 14 Q. Do you mean -- line listing of 15 what? 16 A. Of those patients that would 17 then have been provided to the BGA. 18 Q. Those patients -- 19 A. Who had been suicidal or 20 committed suicide. 21 Q. Did Doctor Wernicke discuss 22 with you that it was the opinion at least of the 23 Lilly employees in Germany, Doctor Schenk and 24 Doctor Weber, that Lilly might have to recommend Page 732 1 a concomitant tranquilizer? 2 A. I was not aware of that. 3 Q. Do you know Doctor Weber? 4 A. I do know Doctor Weber. 5 Q. Hans Weber? 6 A. Uh-huh. 7 Q. Do you have any reason to 8 believe that Doctor Weber was inaccurate in his 9 transmittal of concerns raised by the BGA in 10 Exhibit 22? 11 MR. MYERS: Let we object. That might 12 call on him to speculate as to what Doctor Weber 13 might or might not have done in 1984 when he did 14 not work for Lilly. 15 MS. ZETTLER: I'm asking him if he has 16 any reason to believe that Doctor Weber would 17 have been inaccurate in the way he transmitted 18 the information. 19 MR. MYERS: I'm not arguing, I'm just 20 objecting to the question. If you know and 21 you're able to tell her, tell her. 22 A. The only thing I can think of 23 is that Doctor Weber -- I don't know how concerns 24 that he may have brought to Lilly would have -- Page 733 1 how one translates those concerns from the German 2 language to the English language. So does this 3 fully capture those, I can't say. 4 Q. Can Doctor Weber speak 5 English? 6 A. He can. 7 Q. Can he speak German? 8 A. Yes. 9 Q. And does he understand both 10 languages? 11 A. He does. 12 Q. Is there any reason why he 13 wouldn't be able to translate German into 14 English? 15 A. In my experience as having 16 some talent in another language, I know that 17 there aren't always the right words that capture 18 the expression or the word that one is trying to 19 express, so one word searches. I think Doctor 20 Weber is relatively fluent, his native tongue is 21 German. It's speculative but that's sort of what 22 you asked me to do, speculate. 23 MR. MYERS: Don't speculate anymore. 24 Q. So these could all be Page 734 1 explained by a problem with translation of the 2 BGA's concern from German to English? 3 MR. MYERS: I object to the form, 4 that's not what he said. That's a different 5 question, Nancy, than you asked. 6 A. I don't know, I will be honest 7 with you, I don't know. Not having been a part 8 of that process, I can't really say. 9 Q. Is Doctor Weber a 10 psychiatrist? 11 A. He is not. 12 Q. He's not. What does he 13 specialize in? 14 A. I believe he's an internist. 15 Q. Is he a medical monitor over 16 there, clinical monitor? Is he a clinical 17 monitor in Germany? 18 A. Now? 19 Q. Yes. 20 A. He is I believe the director 21 of the German affiliate. 22 MS. ZETTLER: Okay. Let's take a 23 break. 24 (A SHORT BREAK WAS TAKEN.) Page 735 1 (PLAINTIFFS' EXHIBIT NO. 23 WAS 2 MARKED FOR IDENTIFICATION AND 3 RECEIVED IN EVIDENCE.) 4 Q. Do you recognize Exhibit 23, 5 Doctor? 6 A. I do have a vague 7 recollection, yes. 8 Q. Can you tell me what that is? 9 A. As best I recall, there were 10 some terms that were rarely ever used for which 11 it was felt that an alternative would be 12 appropriate or where the term was not an accurate 13 description. 14 Q. Okay. So it was either the 15 term was rarely used or the term was not an 16 accurate description? 17 A. As best I recall. 18 Q. When you say term you mean an 19 Elect dictionary term? 20 A. Yes, ma'am. 21 Q. So the terms on the left, the 22 deleted terms are the ones that were deleted and 23 replaced with the terms on the right or at least 24 at that time the suggested terms to replace the Page 736 1 terms on the right? 2 A. That would be the case -- I'm 3 sorry. I'm not sure that process was finalized. 4 This would appear to be a working document. 5 Q. The terms anxiety and 6 agitation exist in the Elect dictionary now, do 7 they not? 8 A. They do. 9 Q. Does that suggest to you that 10 they replaced adrenergic syndrome? 11 A. I don't know that that was the 12 outcome. 13 Q. Okay. Do you know when 14 anxiety and agitation were added to the Elect 15 dictionary? 16 A. As far as I know they were 17 always there. It may have been that in this 18 working document there was some sense that some 19 of the terms that were proposed for deletion were 20 easily mapped to another term which was already 21 in the document or in the dictionary. 22 Q. So would this suggest that 23 adrenergic syndrome would become a synonym as 24 opposed to a classification term? Page 737 1 A. That's as I understand would 2 be the action. 3 Q. Okay. How about sexual 4 dysfunction, it says needs clarification in the 5 right-hand column, does it not? 6 A. Yes, it does. 7 Q. Do you know what sexual 8 dysfunction was eventually mapped to or replaced 9 with? 10 A. No, I don't. 11 Q. What was Doctor Wheadon's 12 title when he left Lilly? 13 A. Senior research physician, or 14 senior clinical research physician as best I 15 recollect. 16 Q. Do you recall that you 17 participated in the conference call with the 18 coroner on the Wesbecker case, do you recall his 19 name as being Doctor Greathouse by any chance? 20 A. As I recall, that's what his 21 name was. 22 Q. Was that call, phone call 23 recorded, to your knowledge? 24 A. Not to my knowledge. Page 738 1 Q. A member of the CCHR testified 2 at the coroner's inquest in the Wesbecker case, 3 correct? 4 A. As best I recall. 5 Q. Yes? 6 A. I'm not certain of that, I 7 seem to recollect that there was someone there 8 from CCHR. 9 Q. Who raised the issue of the 10 Church of Scientology with regards to the 11 Wesbecker case, Doctor Greathouse or Eli Lilly 12 employees? 13 MR. MYERS: In that phone call? 14 MS. ZETTLER: Yes. 15 A. As I recall -- the best I 16 recall it was a side sort of a comment that 17 Doctor Greathouse made and that that had not been 18 raised specifically by Lilly prior to that. 19 Q. Do you know how Doctor 20 Greathouse became aware that the Church of 21 Scientology was in any way involved with the 22 media surrounding the Wesbecker case, if they 23 were at all? 24 A. I have no idea. Page 739 1 Q. Besides the consultant meeting 2 that we talked about the other day, did you 3 attend any other meetings of consultants on the 4 issue of violent-aggressive behavior or 5 suicidality on Fluoxetine? 6 MR. MYERS: Consultant meetings? 7 MS. ZETTLER: Right. 8 A. I have a vague recollection, 9 and this is very vague, that when the data 10 analysis suggested by the panel of experts was 11 completed, that there may have been a review of 12 that data with the experts and I may have been 13 there for part of that day, but I don't believe I 14 was there for the full day and that's a vague 15 recollection. 16 Q. Do you know if the issue of 17 the BGA's concern regarding the use of Fluoextine 18 and suicidality was ever raised with the 19 consultants that were gathered on the issue of 20 suicidality? 21 A. I don't recall. 22 Q. Were meeting minutes ever 23 produced as a result of either of the meetings 24 that you attended? Page 740 1 A. I don't recall. 2 Q. Was Doctor Beasley's analysis 3 of the Fluoxetine, Imipramine, placebo trial of 4 Fluoxetine in which he found that there was a 5 trend in agitated patients becoming agitated -- 6 or agitated patients being more prone to 7 activation discussed at consultant meetings? 8 A. I don't recall. 9 Q. To your knowledge, was there 10 ever any review whatsoever of the OUS clinical 11 trial data base with regards to violent 12 aggressive behavior? 13 A. I believe -- to the best of my 14 recollection, I believe we looked at reports that 15 may have been in the DEN that would have existed 16 from clinical trials and from post-marketing. 17 Q. The clinical trials though, 18 themselves, the data bases themselves, to your 19 knowledge was there ever a review of the clinical 20 trial data bases for the OUS clinical trials with 21 regards to violent aggressive behavior? 22 A. I do not recall that we 23 applied the aggression cluster to the OUS data 24 base. Page 741 1 Q. Okay. Do you feel that 2 suicide or suicidal ideation is violent 3 aggressive behavior? 4 A. Suicidal ideation is not a 5 behavior. I think suicidal actions I consider to 6 be self-directed violence. 7 Q. Other than the way the action 8 is directed, either towards yourself or towards 9 others, is there a difference in your mind as to 10 the kind of violent aggressive behavior it is, 11 like suicidality versus other versus an injurious 12 behavior towards others, is there a difference 13 besides who the aggression is directed towards? 14 MR. MYERS: I object to the form of 15 the question because it's -- in addition to being 16 incomprehensible, at least to me, I think it's 17 compound. I think you asked him two or three 18 things. 19 MS. ZETTLER: Let me try a different 20 question. 21 Q. Other than the fact that the 22 violence in suicide is directed towards oneself 23 and obviously a homicide is aggression directed 24 towards somebody else, is there a difference in Page 742 1 your mind in your opinion between the violent 2 aggressive behavior in a suicide and the violent 3 aggressive behavior in a murder, for instance? 4 MR. MYERS: I still object to the 5 form. If you can answer, answer. 6 A. Based upon the question, I 7 think there are some differences. 8 Q. Okay. Like what? 9 A. Some other directed violence 10 would be what I would characterize as impulsive 11 aggressive. Some other directed violence, some 12 significant other component or the other 13 percentage would be premeditated. In my 14 estimation, most self-directed violence is 15 premeditated. 16 Q. Can suicide ever be impulsive? 17 A. I suppose that's possible. 18 Q. Okay. What about in a 19 situation with Joseph Wesbecker where he was 20 violent aggressive towards others and himself, do 21 you feel that there is a different disease 22 process going on or was going on with Mister 23 Wesbecker that produced the violent aggressive 24 behavior towards others and another disease Page 743 1 process that produced the violent aggressive 2 behavior that resulted in the suicide? 3 A. Is that two questions? I'm 4 trying -- 5 Q. No, I think it's one but it 6 may sound like two. What I'm trying to find out 7 is, you know, do you attribute as a psychiatrist, 8 and I know you have limited information on Mister 9 Wesbecker, but in situations such as Mister 10 Wesbecker where somebody commits murders and then 11 immediately commits a suicide, okay, do you as a 12 psychiatrist attribute those two acts, seemingly 13 different acts to different disease processes or 14 are those really just one act in your mind? 15 A. I see it as being, as best 16 with the information I have available in my 17 experience, it would seem to me that that would 18 be the action of a very angry person superimposed 19 upon whatever neuropsychiatric illness may have 20 been preexisting. 21 Q. Okay. So it's really -- it's 22 the same, contributing factors to both events? 23 MR. MYERS: Let me object to the form, 24 I don't think that's what he said. Page 744 1 MS. ZETTLER: I'm trying to clarify 2 it. 3 A. No, I wouldn't say that. I 4 think there are people who are just angry who 5 commit violent acts. I think there are people 6 who are angry that the anger is not necessarily a 7 part of the disease process and they feel 8 slighted or they may be angry at a spouse or 9 something, may choose to take it out on a spouse 10 or someone else. 11 Q. In your opinion, can 12 Fluoxetine cause delusions in some people, cause 13 them to become delusional? 14 A. Delusions in and of themselves 15 without anything else? 16 Q. Well, obviously if you're 17 taking Prozac, you are at least depressed, 18 correct? In most cases, you're suffering some 19 sort of mental illness, right? 20 A. Correct. 21 Q. Okay. I'm saying in that 22 context of a person who's taking Prozac assuming 23 for a mental illness like depression and it 24 causes delusions or they become delusional, have Page 745 1 you ever seen a case where you -- in your opinion 2 the delusions were reasonably, causally related 3 to the use of Fluoxetine? 4 A. Not that I recall. 5 Q. Okay. Can you conceive of any 6 instance where Fluoxetine would cause somebody to 7 become delusional? 8 A. In any estimation it would be 9 very unlikely. 10 Q. Why? 11 A. It just would seem to be a 12 very rare unlikely event if it were to occur. 13 Q. From a medical or psychiatric 14 standpoint why would it be unlikely? 15 A. In my experience as we define 16 delusional behavior, that would not appear in 17 most instances to be a drug related event. 18 Q. Have there been instances 19 where it's been drug related, delusions have been 20 drug related? 21 A. Any drug? 22 Q. Yes. 23 A. I believe delusions as a 24 component of a psychotic episode have been Page 746 1 reported with some substances of abuse. 2 Q. Substance abuse? 3 A. With some substances of abuse. 4 Q. Like what? 5 A. PCP, those are usually 6 shortlived, could be with chronic amphetamine 7 abuse, people might describe some of the behavior 8 when someone is having a LSD crisis as delusional 9 in the context of greater degree of 10 symptomatology. 11 Q. Methadone? 12 A. I don't -- with Methadone? 13 Q. Right. 14 A. I'm not aware. 15 Q. Cocaine? 16 A. I'm not aware but that could 17 be a possibility. 18 Q. Crack cocaine? 19 A. I don't know. 20 Q. When a determination is made 21 that an adverse event is expected, and I 22 understand that that's a regulatory definition, 23 but in your mind does that mean that you expect 24 to see those adverse events with the drug? Page 747 1 A. No, that does not. It just 2 means that to my information I have, it means 3 that the event is listed in the package insert 4 with a marketing compound and with the 5 communication of January, 1993 as also covered in 6 the CIB. 7 Q. An event that is expected, if 8 it's serious can still be reported as an alert 9 event if you get an unusually high number of a 10 certain event at a time, correct? 11 A. I'm sorry, could you repeat 12 that. 13 Q. Let me ask it this way. 14 Suicide is expected as far as the regulatory 15 definition of expected is concerned at this point 16 because it's listed in the package insert on 17 Fluoxetine, correct? 18 A. You're talking about a 19 completed suicide? 20 Q. Right. 21 A. To my knowledge, any death, 22 regardless of whether there's information in the 23 package insert relative to the cause of the 24 death, so let's say a patient is reported to have Page 748 1 died while taking monoamine oxydase inhibitor and 2 Fluoxetine concomitantly, I would assign that, 3 and I'm not sure if there was a change recently, 4 but I would assign that as unexpected. We wanted 5 to be sure that all deaths were sent to the FDA 6 as an alert report. 7 Q. Okay. Let's try attempted 8 suicide, I mean suicide -- attempted suicide is 9 not listed in the package insert, is it? 10 A. I don't believe it is. 11 Q. So if you have a suicide where 12 the outcome is say just hospitalization and it's 13 not death? 14 MR. MYERS: You mean a suicide 15 attempt? 16 MS. ZETTLER: Right. 17 Q. Then unless you get fifteen of 18 them at once or something like that, you're not 19 going to use that -- you're not going to submit 20 that as an alert report, are you, that single 21 suicide attempt? 22 A. No, I think we would submit, 23 if it's a serious and the report -- and the event 24 is not in our package labeling, we would not Page 749 1 await submitting that. If we had a cluster of 2 such events, we would submit one by one by one by 3 one. 4 Q. As alert reports? 5 A. Well, now I'm getting a little 6 bit confused as to what constitutes -- I can't 7 remember if serious, unexpected -- serious, 8 unexpected, possibly related. 9 Q. Reasonably, possibly, causally 10 related? 11 A. Would be an alert report. I'm 12 not sure that serious, unexpected, not related 13 would be an alert report. It would still be 14 filed in a very timely fashion but there's two 15 different definitions. I leave that in the hands 16 of the regulatory folks. I just -- when I have 17 an event, I value that event to the best of my 18 ability with the knowledge I have available. 19 Q. Did somebody from regulatory 20 ever return an adverse event report to you and 21 said this is not an expected event or that it is 22 an expected event? 23 A. That it is expected? 24 Q. Yes. Page 750 1 A. Not that I recall. 2 Q. Has anybody from regulatory 3 returned any adverse event reports to you and 4 asked you to make changes on those forms, other 5 than adding follow-up information? 6 A. Yes. 7 Q. In what circumstances? 8 A. Where the event was a 9 duplication of an earlier event reported. 10 Q. How about changing event 11 terms, have they ever asked you to change event 12 terms? 13 A. There have been within the 14 same day or early the next day, if a research 15 associate questioned an Elect term, a mapping 16 term, that would come back to me, and if I 17 questioned theirs I would send it to them with 18 the notation, I don't think this is an 19 appropriate mapping term. 20 Q. Give me an example. 21 A. I'm trying to remember what 22 would be a good example. Okay. This is very 23 simple and would not be the case but would be one 24 such example. Let's say that a patient reported Page 751 1 nausea and the research associate would have said 2 GI distress, I would send that back or I would 3 scratch out GI distress and say nausea because we 4 have such an event term which is more precise for 5 the event term reported to us. So in that case 6 there would be that kind of a change, if there's 7 something more specific or more accurate that 8 reflects the event. 9 Q. Is suicidal ideation still 10 mapped to depression in the Elect Dictionary? 11 A. I don't recall. 12 Q. Is suicide attempt with the 13 drug still mapped to overdose? 14 A. I don't recall. 15 Q. In your opinion, is mapping 16 suicidal ideation or suicide gesture to 17 depression a more accurate description of the 18 event than just listing it as suicidal ideation? 19 A. One must use the Elect 20 dictionary terms and from time to time there have 21 been periodic updates of that dictionary to make 22 it more reflective of the real world experience. 23 Q. That's not my question. My 24 question is, in your opinion, is mapping suicidal Page 752 1 ideation to depression an accurate description or 2 more accurate description than simply listing 3 suicidal ideation as an adverse event? 4 MR. MYERS: Excuse me, as the Elect 5 term? 6 MS. ZETTLER: Any term. 7 Q. If you were to just have an 8 adverse event reported to you of suicidal 9 ideation, do you in your opinion, feel that it is 10 more accurate to map that term to the word 11 depression or to leave it suicidal ideation? 12 A. It cannot be left, it must be 13 mapped to something, and so one chooses the most 14 accurate term that would describe that and for a 15 time, a period of time that would have been 16 depression. 17 Q. That's still not my question. 18 Whether or not the rules at Lilly or the rules at 19 the FDA require that suicidal ideation at this 20 time or at any time be mapped to depression, my 21 question is, in your opinion, is it a more 22 accurate description of the adverse event to map 23 suicidal ideation to depression or is it a more 24 accurate description just to leave it suicidal Page 753 1 ideation? 2 MR. MYERS: I object to the form, he 3 answered that at least once. 4 MS. ZETTLER: No, he hasn't. 5 A. It's not an option, it's just 6 not an option. If you're saying should the 7 dictionary -- should the FDA revise the 8 dictionary, that would seem appropriate. But 9 that's not an option as it stood at that 10 particular point in time that you may be 11 referring to. 12 Q. So you're saying you agree 13 with that? 14 A. I agree that one should -- my 15 obligation is to pick the best possible term 16 which is available in the Elect Dictionary and 17 leave it to the regulatory component and the 18 legal component, whomever deals with the FDA 19 around revising dictionaries. 20 Q. Have you ever disagreed with 21 anything regulatory has done? 22 A. Have I ever disagreed? 23 Q. Right. 24 A. I don't recall any Page 754 1 disagreements. 2 Q. If you disagreed with 3 something that regulatory asked you to do, would 4 you feel comfortable in raising that issue with 5 regulatory? 6 A. You mean -- that's a question 7 that engages in speculation. I'm very 8 comfortable raising issues of difference. 9 Q. Okay. So let's see if we can 10 get an answer to my original question. In your 11 opinion, is it more accurate to map suicidal 12 ideation as reported as an adverse event as 13 suicidal ideation to the Elect term depression or 14 is it more accurate to report it as the actual 15 event that was originally reported, suicidal 16 ideation? 17 MR. MYERS: I'm going to object to the 18 question for this reason: He's answered it 19 twice, and now you're assuming that they wouldn't 20 report the actual term. I mean you're mixing 21 apples and oranges, Nancy. 22 MS. ZETTLER: No, I'm not, Larry. He 23 hasn't answered it, he's not given me a direct 24 answer. He has not said I agree, I disagree or I Page 755 1 have no opinion. He keeps referring back to the 2 requirement. I want to know what his opinion is, 3 I have a right to ask it. If he doesn't have an 4 opinion, he can tell me he doesn't have an 5 opinion. 6 MR. MYERS: Again, I object to the 7 question because now your question the way you 8 just phrased it assumes that you would not report 9 the actual term in addition to the event term 10 which I think is what has been talked about by 11 this witness and other people ad nauseum in these 12 depositions. Go ahead and see if you can answer 13 that, Doctor. 14 A. I've given you my best answer. 15 Q. So you don't have an opinion 16 either way? 17 MR. MYERS: No, that's not what he 18 said. 19 A. I would say I would abide by 20 the current regulations and the current 21 dictionary. 22 Q. You would follow the rules? 23 A. Absolutely in that case. 24 Q. Is the actual event term used Page 756 1 by the reporter listed on the 1639 that goes to 2 the FDA? Not the working form that's used at 3 Lilly. 4 A. In most instances I believe it 5 would be. 6 Q. Where? 7 A. On the what is usually -- 8 well, the format has changed but on the second 9 page, it may be reflected in the -- if the event 10 term matches the Elect term, it would be listed 11 under the Elect terms that are on the second 12 page. The event as reported by the physician in 13 terms of the narrative would be included there. 14 Q. So in the narrative have you 15 ever seen an occasion where it's said the 16 reporter reported a suicide with drugs? 17 A. Have I ever seen that specific 18 language? 19 Q. Yes. 20 A. I don't recall seeing that 21 specific language. 22 Q. Have you ever seen language on 23 a 1639 in the comment section or any other place 24 in the 1639 that says reporter reports suicidal Page 757 1 ideation? 2 A. Oh, I've seen those kinds of 3 reports, not in those exacts words, but I 4 certainly have seen reports in which the reporter 5 said this patient developed suicidal ideation 6 while taking Fluoxetine in the narrative section. 7 Q. Did Doctor Greathouse ask 8 Lilly for any data regarding the use of 9 Fluoxetine and violent aggressive behavior, to 10 your knowledge? 11 A. Not to my knowledge. 12 Q. Did Lilly provide Doctor 13 Greathouse with any information, written data 14 whatsoever? 15 A. I'm not aware of any. 16 Q. Do you know if the 17 conversation -- I think Paul asked you this 18 yesterday, I apologize. Do you know if the 19 conversation that you were a part of with Doctor 20 Greathouse occurred before or after the coroner's 21 inquest? 22 A. I don't recall. 23 Q. Have you ever been in contact 24 with anybody at the National Institute of Mental Page 758 1 Health? 2 A. Yes. 3 Q. Who? 4 A. Doctor Judith Rapaport and 5 Doctor Henrietta Leonard. Are you talking just 6 about my Lilly career? 7 Q. Yes. 8 A. Doctor Peter Jenson, and 9 Doctor -- and I don't have the name correctly, 10 but it seemed like Benito Vitielo. 11 Q. How about Fredrick Goodwin? 12 A. No. 13 Q. How about Robert Prin, 14 P-R-I-N? 15 A. Yes, I have. 16 Q. Who is Doctor Prin? 17 A. Doctor Prin is a -- as I 18 recall, is a Ph.D who is very interested in the 19 disorders of depression, depressive disorders. 20 Q. That other homicide, the woman 21 in Wisconsin that we were talking about earlier, 22 did that happen before or after the Wesbecker 23 incident? 24 A. To the best of my Page 759 1 recollection, it happened before. 2 Q. How did you become aware of 3 that? 4 A. Through the media coverage of 5 the Wesbecker occurrence. 6 Q. Media coverage of the 7 Wesbecker occurrence? 8 A. Yes. 9 Q. How is it that other thing 10 raised in the media coverage of the Wesbecker 11 occurrence? 12 A. As best I recollect, CCHR 13 discussed that with the media. 14 Q. When? 15 A. After the Wesbecker 16 occurrence, to the best of my knowledge. 17 Q. How long after the Wesbecker 18 occurrence? 19 A. As best I recollect, shortly 20 thereafter. 21 Q. Did you testify yesterday -- 22 and again, I think you did but I can't remember 23 what your answer was -- that you made inquiries 24 as a result of that murder in Wisconsin? Page 760 1 A. Yes. 2 Q. Who did you call? 3 A. The first -- because we had no 4 information other than what had been reported, I 5 contacted a sales representative in Madison and I 6 said we have a report of this event, I want you 7 to go to the library and look through all the 8 newspapers to find out what you can as to whether 9 this event occurred and any information you can 10 provide me. That sales rep did that and called 11 me back with information. 12 Q. Okay. Then what happened? 13 A. Either I or someone as I 14 recall had some contact with the medical examiner 15 in Door County, not Door County, that's whatever 16 county it's in, in Madison, to obtain any 17 additional information. 18 Q. Did you get any information, 19 any additional information? 20 A. As I recall we did get 21 additional information. 22 Q. You did? 23 A. I believe we did. 24 Q. What kind of information? Page 761 1 A. We may have received a copy of 2 the medical examiner's inquest or whoever would 3 do that. 4 Q. Any transcript? 5 A. I have some vague recollection 6 of some information that we had. 7 Q. You stated yesterday that a 8 prison warden has called you about using 9 Fluoxetine in his prison or her prison, correct? 10 A. I recall receiving such a call 11 from a warden, yes. 12 Q. What did you do in response to 13 that call? 14 MR. MYERS: He went over this 15 yesterday. 16 MS. ZETTLER: I think that Paul did. 17 A. As best I recollect, I told 18 him that Fluoxetine was not indicated for the 19 treatment of violence or aggressivity and I could 20 not imagine that we would supply medication 21 outside of indication. 22 Q. Did he ask to talk to anybody 23 else at Lilly? 24 A. He did not. Page 762 1 Q. Was Lilly ever contacted by 2 this person again? 3 A. Not to my knowledge. 4 Q. Do you remember where the 5 prison was? 6 A. I have a vague recollection 7 that it may have been -- this is a very vague, a 8 state warden, a state whatever, corrections 9 officer or whatever for Arizona or New Mexico, 10 but that's very vague. It's from some -- 11 southwest comes to mind. 12 Q. Do you remember the person's 13 name that contacted you? 14 A. No, I don't. 15 Q. To your knowledge, has Lilly 16 or anybody else conducted any studies on prison 17 populations with Fluoxetine? 18 A. I'm not aware of that. 19 Q. Were you aware that Judith 20 Rapaport proposed studying the effect of 21 Fluoxetine generally on inner-city children? 22 A. I'm not aware of that. 23 Q. Would you be for or against 24 such a study, just in the general population of Page 763 1 inner-city kids? 2 A. Without additional 3 information, I couldn't really comment. 4 Q. Do you know how long Joseph 5 Wesbecker was on Prozac the first time he took 6 it? 7 A. No, I don't recall. 8 Q. Do you know what happened as a 9 result of that first time he took Prozac? 10 A. I don't recall. 11 Q. Has Lilly done any studies 12 using Fluoxetine to treat schizo-affective 13 disorder? 14 A. I'm not aware that we have 15 sponsored such studies. 16 Q. Did they consider doing such 17 studies? 18 A. Not that I'm aware of. 19 Q. On what occasion did you feel 20 compelled to fly to a site to investigate an 21 adverse event report? 22 A. There was a report, four or 23 five reports from Toledo, Ohio by a reporter who 24 had had -- seen I believe in consultation women Page 764 1 who had reported increased bruising while taking 2 Fluoxetine and had run some specific studies 3 looking at their clotting mechanism. 4 Q. Any other instances? 5 A. I don't recall any others. 6 Q. Do you know if the questions 7 raised by the BGA that you're aware of, looking 8 at the exhibit that we showed you today, were 9 ever submitted to outside consultants for 10 evaluation? 11 A. I recall that the 12 phospholipidosis question was referred to outside 13 consultants 14 Q. Any others? And I'm not 15 talking about the suicide consultants that were 16 grouped after 1990, I'm talking about others. 17 A. I don't recall others. 18 Q. Were any consultants from 19 outside of the United States used on the 20 suicidality issue as far as you know? 21 A. I'm not aware but I don't 22 know. 23 Q. How about Stewart Montgomery, 24 was he consulted? Page 765 1 A. I don't know. 2 Q. Do you know of a study run by 3 Doctor Montgomery sometime in 1988 to 1990 for 4 use of Fluoxetine as a suicidality prophylaxis? 5 A. I have some recollection of 6 that. 7 Q. Were you involved at all in 8 that study? 9 A. No, I was not. 10 Q. Do you know if that study was 11 actually done? 12 A. I believe we embarked upon 13 that study, I don't know anything further. 14 Q. Do you know if it was 15 completed? 16 A. I don't know. 17 Q. Do you know if it was 18 published? 19 A. I don't know that either. 20 Q. Do you know if he spoke about 21 that at the 1991 drug advisory committee meeting 22 on suicidality and the use of Fluoxetine? 23 A. I don't recall, I don't 24 recall. Page 766 1 Q. You don't recall that he did 2 or you don't recall? 3 A. I don't recall that he did. 4 He may have but I don't recall that he did. 5 Q. You said I believe earlier 6 today that if litigation is pending or could be 7 pending on an adverse event, their regulations 8 don't require an assignment of causality. Do you 9 remember that? 10 A. As I recollect, yes. 11 Q. Who told you that? 12 A. I believe that came from legal 13 and regulatory. 14 Q. Have they ever shown you a 15 regulation that says that? 16 A. Not that I recall. 17 Q. Have they ever pointed you in 18 the direction of a citation of that regulation 19 that says that? 20 A. No, not that I'm aware. 21 Q. Have they ever explained to 22 you the theory behind that or the reason behind 23 that regulation that requires the assignment of 24 causality to an event that leads to or may lead Page 767 1 to litigation? 2 A. No. 3 (PLAINTIFFS' EXHIBIT NO. 24 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to 7 review Exhibit 24? 8 A. I've reviewed it, yes. 9 Q. Do you recognize this exhibit? 10 A. I do. 11 Q. Can you tell me what it is? 12 A. It's a communication from 13 Doctor Masica to me regarding engagement of NIMH 14 speakers or consultants. 15 Q. From Doctor Masica? 16 A. I'm sorry, it was not from 17 Doctor Masica. It was from Douglas Tillman. 18 Q. Who is Douglas Tillman? 19 A. Douglas Tillman was an 20 attorney here at Lilly. 21 Q. Is he with the company 22 anymore? 23 A. He is. 24 Q. Is he still an attorney with Page 768 1 the company? 2 A. He is. 3 Q. The subject matter of the memo 4 is the National Institute of Mental Health 5 speakers or consultants, correct? 6 A. That's correct. 7 Q. And it's dated July 11, 1990, 8 correct? 9 A. That's correct. 10 Q. It says, it is my 11 understanding that based upon previous agreements 12 with marketing and medical, the following rules 13 apply to all arrangements made by Lilly from 14 medical consulting or scientific lecturing by NIH 15 or NIMH employees, correct? 16 A. That's correct. 17 Q. Are you aware of any instances 18 where NIH or NIMH employees were hired or 19 retained in any way by Lilly to do any medical 20 consulting or scientific lecturing for Lilly on 21 Prozac issues? 22 A. I recall that one individual 23 was part of a symposium that we sponsored at one 24 of the national meetings. Page 769 1 Q. Who? 2 A. Doctor Rapaport. 3 Q. Okay. Was she paid for that 4 appearance? 5 A. I don't know. 6 Q. Was it an indicated or were 7 the attendees of the symposium told in any way 8 that Doctor Rapaport was an employee of NIMH? 9 A. I suspect it would have been 10 well known to the audience as well as perhaps 11 listed on the program, her affiliation. 12 Q. Is it appropriate for 13 employees of NIH or NIMH to speak on behalf of a 14 drug company? 15 MR. MYERS: Let me object to the form 16 of the question and the use of the word 17 appropriate to the extent it might call for some 18 sort of a legal conclusion as to what they can or 19 can't do. 20 Q. In your opinion? 21 A. As I recall she was not 22 speaking on our behalf. As I best recollect she 23 was providing data on obsessive-compulsive 24 disorder in children in an educational format. Page 770 1 Q. Was she reporting on a study 2 done on Fluoxetine? 3 A. I don't know. 4 Q. It says, number one, it says 5 the employee must have no duties directly 6 involving Lilly. Do you see that? 7 A. That's correct. 8 Q. What duties would an NIH or 9 NIMH employee have that would be directly 10 involved with Lilly, to your knowledge? 11 A. I have no idea. 12 Q. Number two says, there must be 13 no appearance of conflict of interest. What does 14 that mean to you? 15 MR. MYERS: Before he answers, let me 16 object to the form. That may have some legal 17 import as relates to the federal employees. But 18 if you know, tell her. 19 A. I don't know. 20 Q. Mister Tillman is writing this 21 to you directly, is he not? 22 A. Yes. 23 Q. Do you know why he was writing 24 it to you? Page 771 1 A. Yes, I do. 2 Q. Why? 3 A. Because I had wanted to have 4 Doctor Rapaport come to Lilly and speak to us 5 about child psychiatric disorders and I was 6 thwarted in my efforts by the -- particularly by 7 the regulations that Lilly had and so Doctor -- 8 Mister Tillman put these in detail for me at 9 which point I'm sure I threw up my hands and said 10 I'll just have to ask somebody else. 11 Q. What rules or requirements did 12 Lilly have regarding governmental employees such 13 as Doctor Rapaport coming to Lilly to speak? 14 A. I don't know those rules. 15 Q. You said you were thwarted by 16 them or you felt thwarted by them in your attempt 17 to have Doctor Rapaport come to Lilly and lecture 18 on child psychiatry issues, right? 19 A. That's correct. 20 Q. Which ones thwarted you? 21 A. It was sort of the entire 22 package. Lilly was very strict and as I recall 23 they did not want to have any pretense of 24 conflict of interest and I remember Doctor Page 772 1 Rapaport complaining ad nauseum that we were the 2 only drug company that did this and she had been 3 a consultant for numerous other companies and why 4 were we making it so difficult and I said that's 5 the way it is, that's out of my control. 6 Q. Do you feel that it would have 7 been against the policies of Lilly for an 8 employee of the National Institutes of Mental 9 Health to consult with Lilly on how they should 10 react to questions in the public on Fluoxetine or 11 any other drug that you know of? 12 A. Do I think it would have been? 13 Q. Inappropriate according to 14 Lilly's own policies on this matter? 15 MR. MYERS: I object to the form of 16 the question. 17 A. At this time -- I believe the 18 policies have changed. At this time I would 19 abide by what the company's policies are so I 20 have to trust those individuals who have 21 responsibility for that process and that would 22 have been primarily our legal people so I abide 23 or I would abide by those regulations. 24 Q. Doctor, I know it's getting Page 773 1 late and I know it's been a few days that we've 2 been here, but please listen to my question. 3 Under Lilly's policies as they 4 existed at the time you were trying to get Doctor 5 Rapaport to come to Lilly to lecture consultants, 6 do you think it would have been inappropriate for 7 Lilly or anybody at Lilly to speak with an 8 employee of the National Institute of Mental 9 Health or the National Institutes of Health and 10 advise them on how they should respond to 11 questions posed to them on the issue of 12 Fluoxetine or any other drug manufactured by 13 Lilly? 14 MR. MYERS: Who's responding to who, 15 the people from the NIMH? 16 MS. ZETTLER: The people from the NIMH 17 to say the media. 18 MR. MYERS: Do you understand what 19 she's asking you? 20 A. I think I understand what 21 you're getting at. I think if the communication 22 was to provide information that would be -- that 23 would seem appropriate, information that would be 24 unknown to someone who had been asked to comment Page 774 1 by the media or by some other agency. So that I 2 would think that would be very appropriate for 3 that person to call us and ask for information as 4 much as any other individual would do the same. 5 Q. But it's inappropriate for 6 somebody from NIMH to come to Lilly and lecture 7 on the general subject of OCD or child 8 psychiatry? 9 A. There were some regulations or 10 rules regarding the contractual arrangement for 11 consultants. I don't recall, I would have to -- 12 I'm not a lawyer so legaleze befuddles me 13 sometimes. 14 Q. I'm asking you. 15 A. But I believe there may have 16 been some different rules for somebody who would 17 have done it without any kind of consulting fee. 18 I just don't remember, I don't know. 19 Q. So Doctor Rapaport could have 20 come to Lilly to consult if she didn't get paid? 21 A. I'm not sure, that's possible. 22 Q. Have you ever arranged for 23 anybody from a governmental agency to consult 24 with Lilly on the issue of Fluoxetine? Page 775 1 A. From a federal agency? 2 Q. Or state, any governmental 3 agency? 4 A. I am not aware that I have. 5 Q. Do you understand what is 6 meant by the second page of this exhibit under 7 number ten where it says medical and marketing 8 will coordinate selection of speakers and 9 consultants to avoid excessive use of National 10 Institutes of Health or National Institute of 11 Mental Health employees? 12 A. No, I don't. 13 Q. Do you know what is meant by 14 number nine where it says Lilly will not list the 15 employee's affiliation with the National 16 Institute of Health or the National Institute of 17 Mental Health in product promotion? 18 A. I would take that literally 19 and say that's what it means. 20 Q. Do you know why that is? 21 A. No, I don't. 22 MS. ZETTLER: It's about three minutes 23 to 5:00 and I've got other areas that I need to 24 go over with him, so we're going to have to go to Page 776 1 court and ask Doctor Heiligenstein to come back 2 to finish this up. 3 MR. MYERS: It's our position he's 4 been here for three pretty long, hard days and 5 absent some directive from some court, he's not 6 going to come back for a deposition. We lawyers 7 can take care of that without muddying up the 8 record on it. 9 MS. ZETTLER: Besides the issue that 10 was raised by Paul earlier, Doctor Heiligenstein 11 has been very involved with many, many aspects of 12 the development, testing, promotion and safety of 13 this drug for many years before and after the 14 issue was raised, the issues involved in all of 15 these cases were raised. He's been pointed to by 16 the vast majority of support staff employees that 17 we have deposed to date as having integral 18 knowledge on a bunch of different issues and 19 while I agree it's been a long -- three long, 20 hard days of deposition testimony, not all of it 21 has been genuine. Some of it has been meant to 22 try to evade questioning and a lot of the time 23 spent trying to get him to answer questions 24 directly and we're going to bring him back for a Page 777 1 little more. 2 MR. MYERS: Well, that's your 3 interpretation, Nancy, and what I will say is in 4 fact he has been here three days testifying about 5 in great detail all of the matters which you 6 raised and so instead of us going on and on we'll 7 simply agree again that we disagree and take it 8 up with the appropriate court. 9 (THE WITNESS WAS EXCUSED.) Page 778 1 COMMONWEALTH OF KENTUCKY ) 2 : ss COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 DR. JOHN HEILIGENSTEIN 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 20TH DAY OF 19 JUNE, 1994. 20 MY COMMISSION EXPIRES MARCH 10, 1998 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 779 1 2 E R R A T A S H E E T 3 4 STATE OF ) : SS 5 COUNTY OF ) 6 7 8 I, DR. JOHN HEILIGENSTEIN, THE 9 UNDERSIGNED DEPONENT, HAVE THIS DATE READ THE 10 FOREGOING PAGES OF MY DEPOSITION AND WITH THE 11 CHANGES NOTED BELOW, IF ANY, THESE PAGES 12 CONSTITUTE A TRUE AND ACCURATE TRANSCRIPTION OF 13 MY DEPOSITION GIVEN ON THE 27TH, 28TH AND 29TH OF 14 MARCH, 1994 AT THE TIME AND PLACE STATED THEREIN. 15 PAGE NO. LINE NO. CHANGE REASON Page 780 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. JOHN HEILIGENSTEIN 10 11 SWORN TO AND SUBSCRIBED BEFORE ME THIS 12 _____ DAY OF __________, 1994. 13 _____________________________ NOTARY PUBLIC, STATE OF 14 AT LARGE 15 16 17 18 19 20 21 22 23 24 Page 781 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Page 782 1 EXAMINATIONBY MS. ZETTLER:.......................299 2 EXAMINATIONBY MR. SMITH:.........................368 3 FURTHER EXAMINATIONBY MR. SMITH:.................540 4 CROSS EXAMINATIONBY MR. HARRIS:..................669 5 REDIRECT EXAMINATIONBY MS. ZETTLER:..............672 6 (QUESTION CERTIFIED.)............................451 7 (QUESTION CERTIFIED.)............................451 8 (QUESTION CERTIFIED.)............................646 9 PLAINTIFFS' EXHIBIT NO. 2........................300 10 PLAINTIFFS' EXHIBIT NO. 3........................320 11 PLAINTIFFS' EXHIBIT NO. 4........................334 12 PLAINTIFFS' EXHIBIT NO. 5........................344 13 PLAINTIFFS' EXHIBIT NO. 6........................350 14 PLAINTIFFS' EXHIBIT NO. 7........................492 15 PLAINTIFF'S EXHIBIT NO. 8........................525 16 (PLAINTIFFS' EXHIBIT NUMBER 9....................543 17 (PLAINTIFFS' EXHIBIT NO. 10......................611 18 (PLAINTIFFS' EXHIBIT NO. 11......................611 19 (PLAINTIFFS' EXHIBIT NO. 12......................633 20 (PLAINTIFFS' EXHIBIT NO. 13......................659 21 (PLAINTIFFS' EXHIBIT NO. 14......................664 22 (PLAINTIFFS' EXHIBIT NO. 15......................672 23 (PLAINTIFFS' EXHIBIT NO. 16......................683 24 (PLAINTIFFS' EXHIBIT NO. 17......................687 Page 783 1 (PLAINTIFFS' EXHIBIT NO. 18 WAS .................691 2 (PLAINTIFFS' EXHIBIT NO. 19 .....................704 3 (PLAINTIFFS' EXHIBIT NO. 20......................713 4 (PLAINTIFFS' EXHIBIT NO. 21......................718 5 (PLAINTIFFS' EXHIBIT NO. 22......................719 6 (PLAINTIFFS' EXHIBIT NO. 23......................736 7 (PLAINTIFFS' EXHIBIT NO. 24......................768 8 9 10 11 12 13 14 15 16 17 18 19 Page 784