1 1 NO. 90-CI-06033 JEFFERSON CIRCUIT COURT DIVISION ONE 2 3 4 JOYCE FENTRESS, et al PLAINTIFFS 5 6 VS TRANSCRIPT OF THE PROCEEDINGS 7 8 9 SHEA COMMUNICATIONS, et al DEFENDANTS 10 11 * * * 12 13 14 MONDAY, NOVEMBER 14, 1994 15 VOLUME XXXV 16 17 * * * 18 19 20 21 _____________________________________________________________ REPORTER: JULIA K. McBRIDE 22 Coulter, Shay, McBride & Rice 1221 Starks Building 23 455 South Fourth Avenue Louisville, Kentucky 40202 24 (502) 582-1627 FAX: (502) 587-6299 25 2 1 2 I N D E X 3 WITNESS: JOACHIM WERNICKE, M.D., Ph.D. 4 By Mr. McGoldrick........................................ 5 By Mr. Smith............................................. 39 5 By Mr. McGoldrick........................................160 6 WITNESS: JOHN GREIST, M.D. 7 By Mr. McGoldrick........................................168 8 * * * 9 Hearing in Chambers......................................193 10 Reporter's Certificate...................................225 11 12 * * * 13 14 15 16 17 18 19 20 21 22 23 24 25 3 1 2 A P P E A R A N C E S 3 4 FOR THE PLAINTIFFS: 5 PAUL L. SMITH Suite 745 6 Campbell Center II 8150 North Central Expressway 7 Dallas, Texas 75206 8 NANCY ZETTLER 1405 West Norwell Lane 9 Schaumburg, Illinois 60193 10 IRVIN D. FOLEY Rubin, Hays & Foley 11 300 North, First Trust Centre Louisville, Kentucky 40202 12 FOR THE DEFENDANT: 13 EDWARD H. STOPHER 14 Boehl, Stopher & Graves 2300 Providian Center 15 Louisville, Kentucky 40202 16 JOE C. FREEMAN, JR. LAWRENCE J. MYERS 17 Freeman & Hawkins 4000 One Peachtree Center 18 303 Peachtree Street, N.E. Atlanta, Georgia 30308 19 JOHN L. McGOLDRICK 20 JOHN F. BRENNER McCarter & English 21 Four Gateway Center 100 Mulberry Street 22 Newark, New Jersey 07102 23 * * * 24 25 4 1 The Transcript of the Proceedings, taken before 2 The Honorable John Potter in the Multipurpose Courtroom, Old 3 Jail Office Building, Louisville, Kentucky, commencing on 4 Monday, November 14, 1994, at approximately 9:08 A.M., said 5 proceedings occurred as follows: 6 7 * * * 8 9 SHERIFF CECIL: All rise. The Honorable Judge 10 John Potter is now presiding. All jurors are present. Court 11 is now in session. 12 JUDGE POTTER: Please be seated. Did any of the 13 jury have any difficulty observing the admonition over the 14 weekend? 15 How about you, Ms. Davis-Spalding, did you have 16 any problems? 17 JUROR DAVIS-SPALDING: No. 18 JUDGE POTTER: Doctor, I'll remind you you're 19 still under oath. 20 Mr. McGoldrick. 21 MR. McGOLDRICK: Thank you, Your Honor. 22 23 24 25 5 1 EXAMINATION 2 3 BY MR. McGOLDRICK: 4 Q. Good morning. Let me begin, if I may, going 5 back to one thing quickly. We had an exhibit last week, 6 Doctor Wernicke, which was this time line. I'm going to bring 7 out part of it and start by asking you this question. In 8 various places on this chart the word PADER appears; it 9 appears in 1988; it appears in 1989 a couple of times; 1990 10 couple, three times, and I guess in '92, '93 and '94. Would 11 you tell the jury what PADER means? 12 A. Yes. That stands for periodic adverse drug 13 experience report. 14 Q. And what is that and with whom does it get 15 filed? 16 A. It's a compilation of all the spontaneous 17 adverse-event reports that are collected by the company and 18 compiled and transmitted to the FDA. 19 Q. Is that routinely done? 20 A. Yes. 21 Q. Thank you. Now, Doctor Wernicke, last week at 22 some length we went through a whole lot of stuff about testing 23 and the documents you go through and the dosage studies and 24 other things. Now, today I'd like to go through a little more 25 quickly some other subjects. First, there's been talk in this 6 1 case about questions raised by the BGA, the German FDA I'll 2 call it, Lilly's answers to those questions and whether Lilly 3 made the FDA aware of all that. You have some knowledge of 4 that subject? 5 A. Yes, I do. 6 Q. First of all, let's just get it straight from 7 the top. Did the BGA ask questions of Lilly? 8 A. Yes. 9 Q. Did Lilly answer all those questions? 10 A. Yes. 11 Q. Was one of those questions about suicidality in 12 the clinical trials? 13 A. Yes. 14 Q. Did Lilly answer that question? 15 A. Yes. 16 Q. Did there come a time when Germany approved 17 Prozac for use in depression? 18 A. Yes. 19 Q. Did the BGA ever require a warning that Prozac 20 can cause or increase the risk of suicide? 21 A. No, they did not. 22 Q. All right. Now, let's turn to the other side. 23 Did Lilly provide the FDA with the BGA's questions to Lilly? 24 A. Yes. 25 Q. Did Lilly provide the FDA with Lilly's answers 7 1 to those questions? 2 A. Yes, we did. 3 Q. Did the FDA thereafter approve the medicine? 4 A. Yes. 5 Q. Did the FDA ever require a warning that Prozac 6 can cause or increase the risk of suicide? 7 A. No, they did not. 8 Q. Was one of your responsibilities, among other 9 people, to respond to inquiries from foreign agencies? 10 A. Yes. 11 Q. Did the BGA at some point raise a number of 12 questions? 13 A. Yes. 14 Q. About how many, if you remember? 15 A. I believe there were 22 questions in the first 16 list that we got in 1984. 17 Q. Is it unusual for a governmental agency in any 18 country to ask questions as a company is trying to present a 19 medicine to them? 20 A. Not at all. It always happens, as far as I've 21 seen. 22 Q. Did other countries approve this medicine for 23 use? 24 A. Yes. 25 Q. Approximately how many? 8 1 A. I believe it's about 75. 2 Q. Now, let's return to the BGA for a minute. Did 3 there come a time when the BGA asked the question about 4 suicidality in the clinical trials? 5 A. Yes. 6 Q. Do you recall that issue? 7 A. Yes. We looked into that. 8 Q. Now, if I could maybe have the easel for a 9 minute. 10 A. While you're doing that, let me clarify. When I 11 say that it's usual for countries to ask questions, those are 12 what we call the major countries. Not every one of the 75 13 countries where it's approved ask their own questions, but the 14 big ones, the first ones always do. 15 Q. Okay. Now, I believe there has been testimony 16 in this trial by the Plaintiffs that there were more suicide 17 attempts in the Prozac group in the clinical trials than with 18 the other medicines or the placebo. Do you recall that? 19 A. Yes. 20 Q. Is that true? 21 A. Yes. 22 Q. And, again, referring to the clinical trials, 23 there were how many suicide attempts and any completions in 24 the Prozac group, do you remember that? 25 A. Thirteen. 9 1 Q. Do you remember how many of those were attempts 2 and how many were suicide? 3 A. There was 1 completed suicide, so 12 attempts. 4 Q. And in the other meds, that is, the comparitor 5 medicines against which Prozac was being compared, about how 6 many or how many? 7 A. There was one that was a completed suicide. 8 Q. And in the placebo, how many? 9 A. None, zero. 10 Q. All right. Now, that looks like a big 11 difference; is that right? 12 A. Well, certainly it would appear that way if you 13 just saw that, yes. 14 Q. And did the BGA ask you about those numbers? 15 A. Yes. 16 Q. And did you respond? 17 A. Yes. 18 Q. All right. Why don't you tell the jury the rest 19 of the story about the 13, the 1 and the 0. 20 A. Well, I have some examples. If I could go up to 21 the easel, I think I could illustrate how one looks at that. 22 Q. All right. 23 A. What I did -- those numbers do look large and if 24 one were to look at nothing else -- 25 MR. SMITH: We're going to object to a narrative 10 1 response to the question, Your Honor. We'd like to have it in 2 question-and-answer form so I might have the opportunity to 3 object to anything that's not permissible under the Rules of 4 Evidence. 5 JUDGE POTTER: I think he's right, Doctor. Why 6 don't you sort of tighten up your answer. 7 A. Yes, sir. 8 Q. First of all, tell the jury again, did you 9 answer the question to the BGA about the 13, 1 and the 0? 10 A. Yes, we did. 11 Q. And in explaining what you did to answer that 12 question, explain to the jury the kind of method you need to 13 do to look at those numbers, and use an example if you need 14 to. 15 A. All right. Allow me to illustrate an example, 16 and I just made up some numbers and I'll have to refer to my 17 notes. Let us just suppose that we had two baseball players. 18 This is a totally hypothetical example. We have two baseball 19 players, we'll call them A and B. And we have these two 20 gentlemen sitting discussing their performance over the last 21 year and they're talking about home runs. They say Baseball 22 Player One had ten home runs during the season and Baseball 23 Player Two had only one. That's a tenfold difference, so 24 these -- it looks like Baseball Player A is a much better 25 player and, in fact, that's what one of the gentleman says. 11 1 "Look, my man is a ten times better player than B." Then his 2 friend says, "Well, how many games did these two players 3 play?" Well, it turns out that Player A played five games and 4 Player B played one game. Now, that then brings you to home 5 runs -- let me abbreviate it home runs per game of two and 6 one, twofold difference. Obviously a much bigger difference 7 than the tenfold difference, but still Player Two looks better 8 than Player One. 9 Q. Excuse me, Doctor. You said it was a much 10 bigger difference than the tenfold difference? 11 A. I'm sorry. Tenfold difference is much bigger 12 than a twofold. Two is bigger than one, but obviously it is 13 now put much more in perspective. Then they say, "Well, how 14 many at-bats did these players have," because they only have 15 an opportunity to hit a home run if they get to go to bat. So 16 let's call them at-bats, and this player had ten chances and 17 this one only got to go once. So now what we're seeing is 18 that we have to look at the raw number, but what also is 19 important is how many games these people played and how many 20 chances they had to be at bat. So what we have to do is 21 divide the number of home runs by the number of games times 22 the number of at-bats. And that number ten divided by ten and 23 one divided by one and that equals one, and this one equals 24 one, and now we see that these are exactly the same. 25 Q. So you have to look at more than just the raw 12 1 numbers you start with, but the other facts? 2 A. Absolutely. 3 Q. All right. Now, let's turn to this issue of 4 adverse events with a medicine and the BGA's question 13 in 5 Prozac, 1 with the comparitors and 0 with the placebo, but 6 let's explain how that works in the medical context and give 7 us an example there. 8 A. All right. Let's use the same kind of a setup. 9 We have two drugs and let's say now we're looking at a rash. 10 Q. Is this a hypothetical example? 11 A. This is a hypothetical example but, again, 12 becoming more real. This is the way it's really done and this 13 is the way it has to be done in order to make any sense out of 14 it. Let's just call them events. 15 Q. That's events of rash? 16 A. Events of rash. Let's say there are 100 with 17 Drug A, 15 with Drug B. That's a 6.7 times greater number in 18 A than in B, which if one just looked at this by itself, it 19 would be disturbing. You would say this drug has a lot more 20 rashes associated with it and these numbers to this level that 21 would be true, but now we find out that the number of patients 22 treated was not the same. There were 200 patients in Group A 23 and only 100 patients in Drug B. This is 3.3 times greater. 24 Again, it's still bigger, but only about half the difference 25 that we saw before. Now, we look into this further and 13 1 discover that how much time these patients had on treatment, 2 so let's say average months on treatment, Drug A was 3, Drug B 3 was 1. Now, the proper way to now get to one number is to 4 talk about events per patient year and you're going to see 5 that all over. What that does is put the number of events 6 into the perspective of the exposure or patients times years. 7 So the proper calculation is events per patient year. I said 8 months up here because it just makes it easier, nice round 9 numbers, but it's the same. So this comes out to 2.0 and 1.1. 10 Now, this difference is a little less. Sorry. Above one. 11 Still a little bit bigger, but now you see that's a lot 12 different than 100 to 15, now it's about 2 to 1. 13 Now, the good question is are these numbers 14 really different. The only way you could say whether these 15 numbers were truly different without doing any more is to look 16 at every patient in the whole world that ever got this drug 17 over all time, both of these groups. Well, clearly that's not 18 possible, so what we do is we estimate whether these two rates 19 are really the same or different, but it's not, well, I think 20 they kind of look different; it's a formal statistical 21 comparison. And let me just illustrate that without going 22 through a whole lot of mathematics. What we say is this: We 23 observe a number of 2. What is that number really. Well, we 24 don't know exactly, but what we do is we talk about what we 25 call confidence intervals. What we can say mathematically, 14 1 and this goes to mathematics and statistics that go back over 2 100 years. They say we can be 95-percent sure that this 3 number of 2.0 -- and this is again just now hypothetical but 4 this has been done with the real numbers -- the 2 number is 5 somewhere between, say, 0.2 and 4. In other words, we can say 6 mathematically we are 95-percent sure if we evaluated every 7 patient in the whole world that ever took this drug over all 8 time that 95-percent sure that the real number would be 9 between 0.2 and 4. So that's with Group A. 10 We do the same thing with Group B. Say Group B 11 the confidence interval falls within 0.1 and 1.8 with the 12 observed number being right in the middle. So we have two 13 confidence intervals. If these overlap, they are not 14 significantly different. The more they do not overlap, the 15 more significantly different they become, and there's a point 16 where statisticians and scientists agree that at that point 17 those numbers are significantly different, and that's how it's 18 done. There's a lot of mathematics that goes behind this, but 19 the principle is that one gets these confidence intervals 20 based on the observations and then decides without any 21 prejudice or thinking what it ought to be, whether these 22 numbers are in fact different or not, and that's what happens 23 when we talk about statistical significant difference. 24 Q. Now, Doctor Wernicke, having given the jury the 25 explanation of -- your examples of how you go about this, when 15 1 the BGA asks the question and when we today look at these 2 numbers, 13, 1 and 0, tell us how that analysis goes. 3 A. Now I'm going to put up real numbers. 4 Q. This is really what happened in the clinical 5 trials? 6 A. Exactly. This is really what happened. And 7 you'll see these numbers again. Now, we're talking about 8 suicide and gestures, we're talking about all of these 9 together, or events -- suicide attempts. 10 Q. Is it gestures or attempts, Doctor? 11 A. Well, it's attempts. 12 Q. Why don't we put attempts. 13 A. Let's call them events. This is just like a 14 rash, and I've got my event numbers. 15 Q. And the event we're talking about is either a 16 suicide attempt or a suicide? 17 A. That's right. Fluoxetine, imipramine, doxepin 18 -- these are now tricyclic drug comparitors in the actual 19 clinical trials -- amitriptyline and placebo. That, of 20 course, is what's referred as a sugar pill. The numbers we 21 observed, 13 on fluoxetine; 0 on imipramine; 0 on doxepin; 1 22 on amitriptyline; 0 on placebo. And those are the numbers we 23 started that people said, "Aren't these much higher." In 24 fact, the BGA had asked about 16, but they misread the table. 25 There was some that weren't even in the trial; there was one a 16 1 year after, one on placebo, so the real number we're talking 2 about is 13. 3 Well, let's just now look at the number of 4 patients: On fluoxetine there were 1,362; imipramine, 394; 5 doxepin, 134; amitriptyline, 71; placebo, 378. So that's one 6 thing we've seen we have to consider. 7 Now, the other piece of information we need is 8 how long are these patients treated. Let's look at average 9 months. Just like in the rash example, 4 on fluoxetine; 3 on 10 imipramine; 3 on doxepin; 1 on amitriptyline; 1 on placebo. 11 This is now the average length of treatment. 12 Now, if we make the appropriate calculation, 13 events per patient month or patient year; that's the way it's 14 usually expressed. Comes out to 0.027 for fluoxetine; of 15 course, 0 for imipramine; no events for doxepin, so that's 0; 16 for amitriptyline, it comes out 0.175; and 0 for placebo. So 17 what we see is that in fact fluoxetine is in the middle, 0 for 18 imipramine, doxepin and placebo, then fluoxtine 0.027, and the 19 highest rate was actually with imipramine. 20 Q. Doctor, before you go forward, let me just say, 21 so that is it true that in the top row you have the 13, 0s and 22 1, and that makes the numbers look like that comparison, but 23 if you take all these proper factors into account you get down 24 to the numbers at the bottom? 25 A. That's correct. 17 1 Q. Now, it looks to me like amitriptyline is a lot 2 higher, maybe -- what's that? 3 A. About five times. 4 Q. Seven or something times higher. Does that mean 5 that amitriptyline in this was a lot worse for suicide? 6 A. No, it doesn't because what I haven't put on 7 yet, and this we would have to do for every one, is calculate 8 this 95-percent confidence level. And when one does that, 9 usually one finds that in fact none of these numbers are 10 different. Statistically, these are all the same, the zeros 11 all the way to the .175, and that is mathematically what there 12 is. 13 Q. Now, when the BGA asked the questions did you -- 14 at some point were all of these numbers provided to the German 15 affiliate? 16 A. Yes. The information was all there. 17 Q. And the ability to calculate statistical 18 significance was all there? 19 A. Yes. 20 Q. And did the German government ultimately approve 21 Prozac? 22 A. Yes, they did. 23 Q. Thank you, Doctor. Now, Doctor, is the issue of 24 suicide important in studying depression or an antidepressant? 25 A. Yes, it is. 18 1 Q. Why is that? 2 A. Well, suicide is a major component of 3 depression. It's a very high risk. 4 Q. You mean the people who have the disease and 5 know medicine? 6 A. Yes. 7 Q. Now, when the BGA asked the questions it asked, 8 did Lilly consult with anybody about the issue of suicidality? 9 A. Yes, we did. 10 Q. And what did you do? 11 A. Well, we talked with Doctor George Winniker, who 12 is one of the leading experts on suicide behavior, and we knew 13 that from the literature, from talking to our investigators. 14 He's at University of Iowa. So we called him and said, "We've 15 been asked these questions and although we've done 16 calculations, it doesn't look like there are any more. Help 17 us evaluate this because we're not experts in this area." 18 Q. And did Doctor Winniker and his colleagues at 19 the University of Iowa look at that question for you? 20 A. Yes. They looked at the data that we had. 21 Q. And what did they conclude about any 22 relationship between Prozac and suicidality? 23 A. There was no relationship between use of Prozac 24 and suicidality. 25 Q. All right. Now, let me ask you another question 19 1 that's been raised and I think maybe the BGA raised, too, at 2 the time, and that is this question about whether Prozac is an 3 activating antidepressant. Do you recall that issue being 4 raised? 5 A. Yes. 6 Q. All right. Now, in that connection looking at 7 the question of activation, did you look at concomitant 8 medicines? 9 A. Yes. 10 Q. And you did that -- strike that. Maybe I'll go 11 up to the board again. 12 Could you tell the jury what you did? And I'll 13 try to write it down the best I can. Sorry. I'd better bring 14 this out again first. 15 Please tell the jury what you did in looking at 16 the concomitant medicines in trying to look at the activation 17 question. First of all, explain what a concomitant medicine 18 is. 19 A. It's a medicine that's taken in addition to the 20 study drug, so in the study we've been talking about, the 21 fluoxetine-imipramine-placebo study that would be something 22 taken in addition to. 23 Q. Okay. Now, what did you do? 24 A. We looked at the frequency of use of those 25 concomitant medications, specifically the ones that were 20 1 anti-anxiety or sleep-inducing. 2 Q. Why did you do that? 3 A. Well, the hypothesis was or the question was 4 since fluoxetine is not sedating, do patients who have sleep 5 disturbance or agitation, anxiety as part of their depression, 6 do they need to take these medications to suppress that. So 7 then the hypothesis would be, well, if that is true then you 8 would expect a much higher use of concomitant medications in 9 the fluoxetine group than in the sedating tricyclic drug or 10 even placebo. 11 Q. So to see if people were being activated, you 12 looked at whether the doctors were prescribing the sedatives 13 or the anti-anxiety medicines? 14 A. Yes. 15 Q. And you looked at it in the controlled study? 16 A. Yes. 17 Q. And what did you find? 18 A. That in fact the rates were almost identical. 19 There was no statistically significant difference. In all of 20 the groups about 20 percent of the patients took these 21 medications. 22 Q. And all of the groups, you mean which of the 23 groups? 24 A. Fluoxetine, imipramine and placebo. 25 Q. All right. Now, have I asked you to get the 21 1 exact numbers so we could give those to the jury? 2 A. Well, I wrote them down because I have to 3 remember them. 4 Q. First of all, what should my chart look like 5 here? I've got Prozac here in one column. Then what are the 6 other columns? 7 A. Imipramine. 8 Q. Imipramine, that's a tricyclic? 9 A. Yes. A generally sedating tricyclic. 10 Q. I'm going to just write "imip." And then what 11 else? 12 A. Placebo. 13 Q. Okay. And you were looking for how much of the 14 sleep medicine or the anti-anxiety medicine? Are those 15 sometimes called benzodiazepines? 16 A. Yes. There are others that are not 17 benzodiazepines, also. 18 Q. Okay. So we look for sleep or anxiety 19 medications; is that right? 20 A. Yes. Percent of patients taking those 21 medications. 22 A. All right. 23 Q. All right. And what did you find? 24 A. In the fluoxetine group that 19 percent of the 25 patients took them; in imipramine, 20 percent; and in placebo, 22 1 17 percent. 2 Q. Is activation of this sort and therefore the use 3 of sleep or anxiety medicines to deal with it, part of the 4 disease depression, even without a medicine? 5 A. Yes. 6 Q. So did it surprise you to find 17 percent in the 7 placebo group? 8 A. Not at all. In fact, in further analyses we 9 looked at the use of these over time and we found that a lot 10 of these patients, about the same percent was taken at the 11 very beginning of the study before they ever even entered the 12 study. 13 Q. All right. Let's just stay with these numbers. 14 These numbers look about the same, but you've just taught us 15 that you have to be careful about looking at things. Are they 16 statistically significantly different or are they in fact 17 about the same? 18 A. They are the same statistically. 19 Q. All right. Now, in this look you looked at all 20 of the persons in this study who had -- in each of the groups 21 who had received these medicines; is that right? 22 A. Yes. 23 Q. Now, did you also look at a subgroup of the 24 people in that study? 25 A. Yes. 23 1 Q. What was the subgroup? 2 A. Well, we looked at the patients that had what we 3 call agitated depression, with the idea being if these people 4 already had a lot of these symptoms of depression; insomnia, 5 anxiety, nervousness, would they need even more of these 6 sedating medications because fluoxetine was not thought to be 7 sedating. 8 Q. So you looked at this subgroup of the agitated 9 depressed people? 10 A. Yes. 11 Q. Now, these were people who were agitated, 12 depressed, just part of the disease? 13 A. Right. They came into the studies with those 14 properties, characteristics. 15 Q. And is agitation a part of depression for some 16 people? 17 A. Yes. 18 Q. All right. Now, so let's look at the chart 19 again. This time we're looking at agitated-depressed patients 20 and we're looking for sleep and the anxiety medicine. Same 21 three groups? 22 A. Yes. 23 Q. One is Prozac, second one is -- 24 A. Imipramine. 25 Q. Third one is placebo? 24 1 A. Yes. 2 Q. Is that writing large enough? Now, what did you 3 find? 4 A. In the fluoxetine group, 28 percent of the 5 patients took concomitant sedative or anxiolytic medication; 6 in the imipramine, it was 27 percent; and placebo was 32. 7 Q. Now, Doctor, those numbers again, to my eye at 8 least, look kind of the same. Are they significantly 9 different? 10 A. No, they're not. 11 Q. Not statistically significantly different? 12 A. That's correct. 13 Q. Doctor, imipramine is sometimes said to be a 14 sedating antidepressant. What does that mean? 15 A. Well, that a lot of patients that take it find 16 that it makes them drowsy, sleepy. 17 Q. But the medicines that were used here were sleep 18 and anxiety medicines in addition to the imipramine? 19 A. Yes. 20 Q. Now, is the -- did it surprise you to find 32 21 percent using these medicines in people who weren't taking any 22 medicine? 23 A. Well, not really because we know that this is a 24 part of depression and that those are bothersome symptoms to 25 patients, and sometimes they need something to help them with 25 1 that. 2 Q. Now, Doctor, did -- was the information which 3 you've just described to us provided to the FDA? 4 A. Yes. 5 Q. Was it provided to the BGA? 6 A. Yes. 7 Q. Did each of those bodies approve the medicine as 8 safe? 9 A. Yes. 10 Q. Now, Doctor, did there come a time when -- 11 strike that. 12 These numbers you've just given us in both the 13 agitated-depressed part and in the total group and your 14 earlier numbers -- well, are they numbers which were published 15 at some point? 16 A. Well, the drug-use numbers were published, 17 certainly not the baseball example, not all that stuff. 18 Q. Oh, no. I'm just talking about the Prozac and 19 the sleep and anxiety, this one that I showed and the others 20 over here, were they published? 21 A. Yes. Yes. They were published. 22 Q. In a peer-reviewed journal? 23 A. Yes. 24 Q. Now, Doctor, did there come a time later when 25 the FDA asked if you would take a look at Prozac in this 26 1 agitated-depressed group to see if it made their conditions 2 better or worse? 3 A. Yes, we were asked that. 4 Q. And approximately when were you asked that? 5 A. That was part of the approval letter. When we 6 got the final approval they asked us to at some time do an 7 analysis to look at that and I believe one other issue. 8 Q. And did you do that? 9 A. Yes, we did. 10 Q. And did you provide the answer to the FDA? 11 A. Yes. 12 Q. And what were the general overall results of 13 that? 14 A. Well, that in fact fluoxetine worked very well 15 for agitated patients, and in the major studies we looked at, 16 in some cases even better than the imipramine. 17 Q. Now, you're comparing it with the sedating -- in 18 the agitated-depressed group, you compared it with the 19 sedating antidepressant and Prozac worked as well or better? 20 A. Yes. 21 Q. Did you report that to the FDA? 22 A. Yes, we did. 23 Q. Did you in short answer their question? 24 A. Yes. 25 Q. And was that data, do you recall whether that 27 1 was published? 2 A. I'm not quite certain right now. I would have 3 to look at the papers. 4 Q. All right. Well, we can find that out. 5 A. I know that concept was dealt with but whether 6 those exact numbers were published, I don't know. 7 Q. Okay. Were the issues that were raised by the 8 BGA that we've been talking about this morning and Lilly's 9 responses to those issues also provided to the FDA? 10 A. Yes. 11 Q. All right. I want to show you a document, if I 12 can, that's been marked Defense Exhibit 177. 13 Your Honor, I believe this is in evidence, so 14 the ladies and gentlemen of the jury should have it. Okay. 15 Now I have it straight. 16 Let me show you 177, Doctor, and let me ask you 17 what that is. 18 A. This is a letter to the FDA dated March 12th, 19 1985. And it's a transmission of -- it's a part of a report 20 called IND Annual Report and it lists what's in this report. 21 Q. Okay. So it's to the FDA from Lilly; is that 22 right? 23 A. Yes. 24 Q. And that's dated February 1985? 25 A. Yes. 28 1 Q. Now, is the whole report that's contained here 2 in that letter, the attachment there? Let me ask the question 3 differently. You've got a cover letter? 4 A. Yes. 5 Q. It says that there is an attachment? 6 A. Yes. There are a number of appendices to this. 7 Q. Are all of the appendices there or just the 8 index? 9 A. What I have here is just one -- a part of one of 10 the appendices. 11 Q. And let me ask you this: Does this appear to be 12 the whole thing? 13 A. (Reviews document) It appears to be. 14 Q. I won't ask you to look through every page. For 15 the record, the jury has the cover but not the whole, big 16 thing at this point. Now, Doctor, were the answers to the 17 BGA's questions in connection with that exhibit? 18 A. Yes. This exhibit contains the questions from 19 the BGA. 20 Q. Okay. Now let me jump ahead a little. Was 21 there some confusion, Doctor, about communication with the FDA 22 about what the BGA meant by the phrase unacceptable damaging 23 effects and severe organ damage? 24 A. Yes, there was. 25 Q. Let's get one thing clear. Whatever else, did 29 1 the company tell the FDA what these terms meant? 2 A. Yes. 3 Q. Now, perhaps I could have Exhibit 67. This is 4 again in evidence; it's Plaintiffs' Exhibit 67. Now, would 5 you tell the jury what that is, sir? 6 A. This is a letter dated October 26, 1987, from 7 Doctor Talbott to the FDA in response to the FDA's wanting to 8 have a discussion of all foreign regulatory activity. 9 MR. McGOLDRICK: With the Court's permission, 10 this is in evidence already. I wonder if I could ask that 11 another copy just be handed out. 12 SHERIFF CECIL: (Hands document to jurors). 13 Q. All right. We'll work off this one, Doctor 14 Wernicke. If I may come up here, Judge. 15 Doctor Wernicke, first, what is the first page 16 of that exhibit? 17 A. It's a transmittal letter. 18 Q. From whom to whom? 19 A. From Doctor Max Talbott to the FDA saying that 20 this is the report that they had asked for. 21 Q. All right. Now, I'm going to call your 22 attention to -- these pages aren't numbered as such except 23 with the PZ number on the side, but I'm going to call your 24 attention to what's the third page, and does that have a title 25 at the top? 30 1 A. Yes. It says, "Actions taken by other national 2 regulatory authorities." 3 Q. And this is your thing you sent to the FDA? 4 A. Yes. 5 Q. All right. Now, I'll call your attention to -- 6 let's see -- the seventh page. I think it's on the side, it 7 says PZ 65 1967. And does this page and the next page 8 contain -- I'm sorry. I think it's PZ 65 1967. 9 JUROR BAILEY: Ours are 164 something. 10 JUDGE POTTER: Madame Sheriff, will you pick up 11 the 67s or one of them so he'll know what we're dealing with. 12 Q. All right. I think we have it clear. The page 13 that has at the top, "Actions taken by other regulatory 14 authorities," that's Page PZ 65 1963 or -4? 15 JUDGE POTTER: It's your problem. Do you want 16 my sheriff to collect them all up? 17 MR. McGOLDRICK: I think if Your Honor could, 18 that would be best. Let me try this, Judge. 19 JUDGE POTTER: Why don't you use the TV thing. 20 MR. McGOLDRICK: Maybe I'll move this out of the 21 way and use the TV, and we'll get these copies out to the 22 jury. All right. Let me see if I can work with this machine 23 here. All right. This is going to be hard to see, but I'll 24 zoom in when it comes time. 25 MR. SMITH: May we approach the bench, Your 31 1 Honor? 2 JUDGE POTTER: Uh-huh. 3 (BENCH DISCUSSION) 4 MR. SMITH: I need to sit over so I can see what 5 he's doing, but I can't sit in Joe's lap. Can Mr. Freeman 6 come over? 7 JUDGE POTTER: We'll break the one-chair rule. 8 I had an extra chair brought in and Mr. Myers took it. 9 They're far enough away from the jury box. 10 (BENCH DISCUSSION CONCLUDED) 11 Q. All right. Now, I'm going to give you another 12 copy of Plaintiffs' Exhibit 67, and I should have one. Let's 13 show they're the same. All right. Now, Doctor, first of all, 14 let's start from the top. This is the cover letter, 15 Plaintiffs' Exhibit 67 and this is -- who is it to? 16 A. It's to the FDA from Doctor Max Talbott. 17 Q. And the date? 18 A. October 26, 1987. 19 Q. There. Okay. Now, let me call your attention 20 to I guess what's the next page on this document, which I'd 21 better zoom down again. At the top what does that say, sir? 22 A. "Actions taken by other national regulatory 23 authorities." 24 Q. All right. And this is the document in which 25 you were reporting to the FDA about other regulatory 32 1 authorities? 2 A. Yes. 3 Q. All right. Now, I ask you to leaf ahead a few 4 pages until we come -- there's England. Let's come to Germany 5 where it says, "German regulatory correspondence." See where 6 it says that at the top? 7 A. Yes. 8 Q. Let me just zoom that page down so the jury can 9 see that. Okay. That's that whole page and at the top, that 10 says, "German regulatory correspondence." Now, on that page 11 and the next page, what are all those things with numbers 12 listed on the side? 13 A. Those are the questions that were asked of us in 14 1984 by the BGA. 15 Q. Okay. And this is your letter sending those 16 questions to the FDA? 17 A. Yes, for the second time, actually. Because we 18 had submitted those questions also in '85. 19 Q. In that big pile that I just handed you? 20 A. Yes. 21 Q. Now, turn to the next page or I guess the second 22 page there and there is a section in there that says 23 "Additional questions." Do you see that, Doctor? 24 A. Yes. 25 Q. All right. Now, under that there are listed 33 1 additional questions; is that right, sir? 2 A. Yes. 3 Q. All right. Now, let's turn over to the next 4 page, the top, the additional questions continue; is that 5 right, sir? 6 A. Yes. 7 Q. All right. Let's look at the first additional 8 question and this is one of the BGA's questions and let's look 9 at the last line of that first carryover item, I guess. You 10 can read the whole thing, if you like. What do those words 11 say at the end? It says Number Two on the left. Do you see 12 it? 13 A. On the top left. 14 Q. Yes. 15 A. Okay. "For the drugs concerned, there is 16 according to their specified profile of adverse effects, the 17 justified suspicion that they have unacceptable damaging 18 effects." 19 Q. All right. And then under that, numbers 2.1, 20 2.2 and 2.3, are explained, various other questions they have 21 may be under that category; is that right, sir? 22 A. Right. It appears now to be an explanation of 23 what they mean by unacceptable damaging effects. 24 Q. All right. And they go on and in the first 2.1, 25 they ask the question whether there is an increased risk of 34 1 suicide; is that right, sir? 2 A. Well, it's written as a statement, not as a 3 question. 4 Q. But these are, in effect, questions that you 5 answered, did you? 6 A. Yes. 7 Q. You sent the answers over to Germany? 8 A. Yes. 9 Q. And after you sent those over to Germany, they 10 approved the medicine? 11 A. Yes. Sometime later. 12 Q. Now, in the next -- next category there's an 13 issue or a question raised about agitating effects; is that 14 right, sir? 15 A. Yes. 16 Q. And then in the next category there's a question 17 about anxiety, insomnia and agitation; is that right, sir? 18 A. Well, that's part of the second question. 19 Q. Right. These are all subheads of that second 20 question? 21 A. Yes. 22 Q. All right. Now, just to go back, the FDA asked 23 these questions -- excuse me. Strike that. 24 The BGA, the German government asked these 25 questions; is that right? 35 1 A. Yes. 2 Q. You provided the answers? 3 MR. SMITH: I'm going to object to the continued 4 leading questions. 5 JUDGE POTTER: Sustained. 6 Q. Withdrawn. Did you provide the answers to the 7 BGA? 8 A. Yes. 9 Q. Is this letter an example of sending the 10 questions to the FDA? 11 MR. SMITH: Same objection, leading, Your Honor. 12 Q. Did you send the questions that the BGA asked to 13 the FDA? 14 A. Yes, we did. 15 Q. And is one of the methods this letter? 16 A. Yes. 17 Q. Thank you. 18 Judge, at an appropriate time when I can get 19 them together, we'll get this document to the jury. 20 JUDGE POTTER: If they already have it, we've 21 kind of developed a policy that you only get to put it in 22 once. 23 MR. McGOLDRICK: All right, sir. It's No. 67. 24 Doctor, did there come a time in 1985 when there 25 was a psychopharmacology advisory committee meeting with 36 1 respect to Prozac? 2 A. Yes. 3 Q. And very briefly -- the jury's already heard 4 this -- what is the committee and what's it composed of? 5 A. They're a group of outside experts that the FDA 6 calls to give them recommendations about the drug. 7 Q. This was in 1985? 8 A. Yes. 9 Q. What was the question which the FDA asked all 10 these experts in 1985? 11 A. There are two questions: Is this drug safe and 12 is it effective. 13 Q. And this was in '85? 14 A. Yes. 15 Q. What did this panel of experts say? 16 A. They unanimously concluded that it was safe and 17 effective. 18 Q. Okay. Do you recall the precise questions that 19 were asked at that time? 20 A. Not the exact words, but that's how it's 21 phrased. The FDA approaches it, they present their analysis, 22 sometimes the sponsor speaks. I believe we give a summary. 23 Then the FDA asks the committee, what is your opinion, is this 24 drug safe, is it effective, should it be approved. Do you 25 recommend approval is the way they often phrase it. 37 1 Q. So whatever the way the question was phrased in 2 1985, this committee was asked to look at this issue and 3 advise the FDA with respect to this medicine and whether it 4 should be approved? 5 A. That's correct. 6 Q. Did they recommend anything with respect to 7 approval? 8 A. They recommended that it be approved. 9 Q. Did you later provide -- later provide the FDA 10 with a further safety update with additional information? 11 A. Yes, we did. 12 Q. And approximately when did you do that? 13 A. I think that was in 1986. 14 Q. And approximately how much more information had 15 been accumulated by then as measured by the books you sent? 16 A. Well, we sent a submission that was actually 17 larger than the original NDA, in about 200 volumes. 18 Q. And thereafter did the FDA have any other 19 questions? 20 A. Yes. There were a few more questions that 21 followed that. 22 Q. Is this is a normal process in an FDA regulatory 23 situation? 24 A. Yes. 25 Q. Did you answer those questions? 38 1 A. Yes, we did. 2 Q. And did the FDA approve the medicine? 3 A. Yes. 4 Q. And approximately when was that, unless you 5 remember exactly? 6 A. December 1987. 7 Q. Okay. Doctor Wernicke, have you ever had an 8 occasion where you personally prescribed Prozac for a patient? 9 A. Yes. Several times. 10 Q. Can you just tell us a couple of those? 11 A. When I was a neurology attending at Indiana 12 University -- 13 MR. SMITH: May we approach, Your Honor? 14 JUDGE POTTER: All right. 15 (BENCH DISCUSSION) 16 JUDGE POTTER: Where are you going with that? 17 MR. McGOLDRICK: I'm just going to ask about a 18 couple of occasions where he prescribed the medication and if 19 he had any problems with it. 20 JUDGE POTTER: Okay. I'm going to sustain the 21 objection. 22 (BENCH DISCUSSION CONCLUDED) 23 Q. Doctor, do you have an opinion as to whether 24 Prozac is safe and effective? 25 A. Yes, I do. 39 1 Q. What is that opinion, sir? 2 A. That it is safe and effective. 3 MR. McGOLDRICK: Cross-examine, Your Honor. 4 JUDGE POTTER: Mr. Smith, do you want to start 5 now or do you want to take a morning recess? 6 MR. SMITH: Why don't we leave it up to the 7 jury. 8 JUDGE POTTER: Let's go ahead and take a morning 9 recess; it's just a good time to break. 10 As I've mentioned to you-all before, do not 11 permit anybody to talk to you about this case; do not discuss 12 it among yourselves, and do not form or express opinions about 13 it. We'll take a 15-minute recess. 14 (RECESS) 15 SHERIFF CECIL: The jury is now entering. All 16 jurors are present. Court is back in session. 17 JUDGE POTTER: Please be seated. Doctor, I'll 18 remind you you're still under oath. 19 Mr. Smith. 20 21 EXAMINATION 22 23 BY MR. SMITH: 24 Q. Doctor Wernicke, is it your position that Eli 25 Lilly and Company fully and completely disclosed to the United 40 1 States Food and Drug Administration what the German government 2 meant by unacceptable damaging effects? 3 A. Yes. 4 Q. Let me show you what's been marked as Exhibit 5 170, Doctor Wernicke, and is already in evidence. Take a 6 minute to look at that. 7 Your Honor, I have some extra copies. 8 JUDGE POTTER: Was that on the list they were 9 going to bring? 10 JUROR BAILEY: Yes. 11 JUDGE POTTER: Okay. They've got it, Mr. Smith. 12 Q. Have you had an opportunity to review Exhibit 13 170, Doctor Wernicke? 14 A. Yes. 15 Q. Now, you and I have talked about this exhibit 16 before, haven't we? 17 A. Yes. 18 Q. And this is a letter to the Food and Drug 19 Administration dated December 4th, 1987, is it not? 20 A. Yes. 21 Q. And it's authored by Doctor Max Talbott, who at 22 the time was the director of medical regulatory affairs, was 23 he not? 24 A. Yes. 25 Q. He was the primary liaison between Eli Lilly and 41 1 Company and the United States Food and Drug Administration, 2 wasn't he? 3 A. Yes. 4 Q. Do you know that he's still employed by Eli 5 Lilly and Company? 6 A. As far as I know. 7 Q. And is still in Indianapolis, Indiana? 8 A. As far as I know. 9 Q. Two hours up Interstate 165 (sic)? 10 A. I haven't driven it, but I've heard that that's 11 about how far it is, yes. 12 Q. Look in the second paragraph in Doctor Talbott's 13 letter to the Food and Drug Administration. The last sentence 14 there says, "In February 1985 in response to this submission, 15 the BGA alluded to unacceptable damaging effects. This phrase 16 was not defined." Correct, sir? 17 A. That's what it says, yes. 18 Q. And there Doctor Talbott is advising the Food 19 and Drug Administration specifically in response to a specific 20 question that the FDA had asked Lilly about this issue raised 21 by the German BGA; correct, sir? 22 A. Yes. 23 Q. And he tells them in this letter of December 24 4th, 1987, that the BGA didn't define it; correct, sir? 25 A. That's what this letter says, yes. 42 1 Q. We have already introduced, Doctor Wernicke, 2 Exhibit 171. Take a look at that, would you please, sir. 3 That's Exhibit 171; correct? 4 A. Yes. 5 Q. And, again, you and I talked about this in your 6 deposition in Houston, Texas, did we not? 7 A. Yes. 8 Q. This is a memoranda, apparently, written in 9 connection with the letter that Doctor Talbott had wrote to 10 the FDA; correct, sir? 11 A. Yes. 12 Q. And this memoranda is talking about that letter 13 and about this issue, isn't it, sir? 14 A. Yes. 15 Q. The second paragraph there says the letter -- 16 that's the letter from Doctor Talbott; correct? 17 A. (Nods head affirmatively). 18 Q. Asserted that the German authorities never 19 defined or documented the phrase severe organ damage or 20 unacceptable damaging effects which were used in their 21 communication to the company. The letter denied that any such 22 organ damage has ever occurred in fluoxetine-treated patients; 23 correct, sir? 24 A. Yes. That's what it says here. 25 Q. Well, that wasn't true, was it, that the letter 43 1 from the BGA never defined unacceptable damaging effects, was 2 it? 3 A. This is a result of a confusion that we talked 4 about earlier, and what's missing here is the word "other." 5 The way that I interpret this, now looking at all the 6 documents, I know exactly how this happened and I'll be more 7 than happy to explain it because I now understand why there 8 was confusion. 9 Q. Well, you know, did you do anything at the time 10 to clear up this confusion? 11 A. Yes. I asked Doctor Weinstein to communicate 12 with the German affiliate to ask if there was anything else 13 that was meant by severe organ damage other than the 14 elevations in laboratory abnormalities and the issues that we 15 had discussed and analyzed with the FDA and the BGA. 16 Q. We're not talking about severe organ damage, are 17 we? We're talking about unacceptable damaging effects, aren't 18 we? 19 A. Well, we are now but in my mind when -- I am 20 responsible for this confusion, and I understand now why I was 21 confused because I never saw those words unacceptable damage 22 in that context, and in my mind that was all the same issue. 23 I thought they were all just talking about organ damage and we 24 had, in fact, submitted all that to the FDA and the BGA. So 25 in my mind there was nothing else beyond that. 44 1 Q. Well, actually, what the letter that -- the 2 definition that the BGA gave you in Plaintiffs' Exhibit 67 has 3 to do with -- on Page PZ 1650 of Plaintiffs' Exhibit 67, do 4 you still have that in front of you, sir? 5 A. No. 6 Q. Can I approach the Witness to show him, Your 7 Honor? 8 JUDGE POTTER: Sure. 9 Q. If we go up there, Item Two doesn't say a thing 10 about organ damage, does it? It talks about they have 11 unacceptable damaging effects, doesn't it? 12 A. In this letter that's what it says, yes. 13 Q. Well, that's the letter we're talking about. 14 That's where the phrase was raised, wasn't it? 15 A. Yes. But I didn't see that letter until all 16 these depositions and all this. When I was asked that 17 question, in my mind that was all the same thing, and I was 18 responding to severe organ damage and unacceptable damaging 19 effects all in the same context because I didn't see that. I 20 never had that. 21 Q. You were the medical monitor in connection with 22 this drug at that time, weren't you, sir? 23 A. Yes. 24 Q. And you were responsible in large part for 25 getting this drug approved, weren't you, sir? 45 1 A. I certainly contributed to that process. 2 Q. And you had been given a great deal of 3 responsibility in this drug, hadn't you? 4 A. I would say so. 5 Q. And Doctor Talbott was looking to you to give 6 him those answers, wasn't he? 7 A. He asked me questions and I provided the answers 8 that I had available to me. 9 Q. And actually it's very important now because the 10 definition that the German government gave was 2.1, "The use 11 of the preparation seems objectionable as the increase in 12 agitating effect occurs earlier than the mood-elevating effect 13 and, therefore, an increased risk of suicide exists." 14 Correct, sir? 15 A. Yes. 16 Q. And that's important, isn't it? 17 A. Yes. The FDA -- 18 Q. That's involved in this -- 19 MR. McGOLDRICK: I wonder if he might finish. 20 JUDGE POTTER: Let him finish his answer. 21 A. The FDA had all of those definitions and that's 22 what I think even now, and that was that -- my own 23 interpretations, what else did they mean, since they had all 24 of those words -- 25 Q. The thing is Doctor Talbott was writing them at 46 1 the time. They had I think Doctor Thompson said 2.5 million 2 pages of documents that this was stuck in, and they were 3 specifically asking about this and Doctor Talbott was 4 specifically responding to them, wasn't he? 5 A. Yes. 6 Q. And he said they didn't define it, didn't he? 7 A. He said that because -- that was my memory -- 8 that there was no further definition of severe organ damage. 9 Remember that I gave Doctor Talbott that information and in my 10 mind, not having seen that 2 and 2.1, .2 and .3, it was all 11 part of the same question. 12 Q. Wait a minute. You hadn't seen this? 13 A. That's what I've said before; that I had at that 14 time had not -- at least I don't remember at the time of the 15 deposition that I had seen that. In thinking back on it 16 further, I still don't remember ever having seen that exact 17 language at the time all of this communication went on with 18 the FDA, and that's why I was confused and concluded that it 19 was all part of this organ damage that we had discussed and 20 analyzed in great detail. 21 Q. You had been the medical monitor for this drug, 22 responsible for this drug since 1984; is that right, sir? 23 A. I was one of the people that was working on it 24 and responsible for it, yes. 25 Q. You were as responsible as anybody was within 47 1 the medical component, weren't you, sir? 2 A. I would say that to a large degree, yes. 3 Q. And you're telling this jury you weren't aware 4 that the German government had raised this issue? You had 5 worked on it and done a response to it, hadn't you, Doctor 6 Wernicke? 7 A. Let me answer the first question. You asked me 8 if I was aware whether they had dealt with that issue and, 9 yes, of course, I was aware of that and we did answer that 10 when we submitted all of that information to the FDA. The 11 question is was I aware of that exact language and the answer 12 to that is no. But, yes, I was aware of that issue. 13 Q. Why didn't you go back to the response that you 14 had filed with the BGA that purportedly you had filed with the 15 FDA and look it up and made yourself completely aware of what 16 you had done to respond to this? 17 A. Because I know that we had submitted all of that 18 information to the FDA and much, much more. 19 Q. But they were asking you for the answer to a 20 question, weren't they, Doctor Wernicke? Doctor Talbott came 21 to you and said, "The FDA wants to know what the BGA means by 22 unacceptable damaging effect," didn't he? 23 A. No. Actually that's not the way it happened. 24 The way it happened was that there was a telephone conference 25 of which I participated. The FDA asked a number of questions 48 1 and one of them was, "By the way, what does the BGA mean by 2 these words?" 3 Q. So the FDA asked you directly? 4 A. There were a number of us involved in that 5 telephone conversation. 6 Q. And it's your testimony that you were confused, 7 you didn't go look it up to give them the proper definition? 8 A. My testimony is that my memory of this back to 9 1984 and '85 was that this had to do with laboratory 10 abnormalities and possible organ damage and that we had 11 answered all of that to the BGA and, furthermore, that we had 12 done a very, very comprehensive analysis with much more data 13 and had submitted all of that to the FDA. 14 Q. When they talked to you did you tell them go 15 back and look at this submission that we made back in 1985 and 16 you'll get the answer; we set it out in toto? 17 A. I don't usually tell the FDA to go and do 18 something. 19 Q. They asked you to give them the answer, didn't 20 they? 21 A. They asked if we had any information about what 22 that could mean. 23 Q. And you did? 24 A. I gave them the answer that I knew at that time 25 and that we had discussed all of that and that was answered to 49 1 the BGA and I knew that they had been given that information 2 and that we had dealt with all of those issues again in a much 3 more comprehensive analysis. 4 Q. But you didn't point them to it. You told 5 Doctor Talbott to tell them they didn't define it, didn't you? 6 A. As I remember, there was no further definition, 7 but all of those words, all of those definitions were in 8 material we submitted to the FDA, at least once. 9 Q. I know that, Doctor Wernicke. I know that it's 10 there, in here, which was part of 2.5 million pages of 11 documents. And your United States Food and Drug 12 Administration was asking you as the proponent, sponsor of 13 this drug 3 days before it -- or 13 days before it was finally 14 approved by the Food and Drug Administration, they were asking 15 you these questions? 16 A. Yes. 17 Q. And I mean, this was something that was a final 18 question they wanted to know, wasn't it? 19 A. Yes. 20 Q. And this was something that stood between this 21 drug being approved by the FDA, this issue, they called you 22 and you were on a conference call with them, weren't you? 23 A. No. I would not agree with that, that that was 24 the issue that stood between the drug and approval; this was 25 just one of the loose ends that they wanted to tie up. 50 1 Q. It was certainly one of the last questions they 2 asked before you got word that they had approved the drug, 3 wasn't it, Doctor Wernicke? 4 A. I would have to look at the documents. I 5 remember that we -- 6 Q. You have it in front of you. 7 A. But I don't have all of the other documents that 8 go between that date and the approval, including any safety 9 updates that we may have sent in the last few weeks. I know 10 that there was a lot of activity at that time and I can't 11 testify that this was the last communication. And it may be, 12 I just don't know. 13 Q. Will you agree with me, this was one of the last 14 communications? 15 A. Yes. 16 Q. This was one of the last telephone conversations 17 you had with them there in December 1987 before it was 18 approved in December 1987, wasn't it? 19 A. As I remember, that it was one of the last ones. 20 Q. And the United States Food and Drug 21 Administration specifically wanted to know what the Germans 22 meant by unacceptable damaging effects and you told them that 23 they hadn't defined it, didn't you? 24 A. To the best of my knowledge there was no 25 definition beyond what we had submitted, and that is the 51 1 context in which I answered that question. 2 Q. But you didn't tell them to look at what you had 3 submitted; you said it wasn't defined, didn't you? 4 A. Defined any further. The reason I don't feel 5 that that's even relevant is because those questions in 1984 6 were based on what was in the original NDA and, remember, we 7 had done that very comprehensive safety review. 8 Q. But, see, you didn't tell the FDA -- you didn't 9 point them back to that, did you? 10 A. I don't believe I need -- 11 Q. You said the Germans didn't define it. 12 A. I don't believe that I needed to point the FDA 13 to that. 14 Q. You don't think so when they were calling you 15 and asking you a specific question about a specific item? 16 A. No. I don't feel that I need to point to that. 17 What I felt and still do need to do is to tell them what my 18 opinion and information was on that issue at the time. 19 Q. That was wrong, wasn't it, at best? 20 A. I don't think it was wrong. 21 Q. It was either a mistake on your part or it was a 22 misrepresentation on your part, wasn't it? 23 A. The most it was was that I had not seen those 24 words "severe damaging effects" and thought that this was all 25 the same, but I would remind you that all of the documents and 52 1 all of the words had been submitted to the FDA so -- 2 Q. I know that. I know that. They knew that. 3 They knew they had something, but the Food and Drug 4 Administration was calling and asking about this particular 5 phrase, "unacceptable damaging effects," weren't they? 6 A. Yes. 7 Q. And Doctor Talbott, based on your information, 8 said this phrase was not defined, didn't he? 9 A. That's what he said, yes. 10 Q. And then in the -- you know it was relied on by 11 the FDA because they referred to in Exhibit 171, "Your letter 12 says unacceptable damaging effects was not defined," don't 13 they? 14 A. Yes. 15 Q. And then approval was granted a few days later; 16 correct, sir? 17 A. A few weeks later. 18 Q. Well, that may have been in some of this two and 19 a half million pages of documents that was submitted to the 20 FDA, and maybe with a real diligent search on the part of the 21 FDA they might have been able to find it, but do you have 22 exhibit -- Plaintiffs' Exhibit 64 in front of you, Doctor 23 Wernicke? 24 A. No, I do not. 25 Q. This goes back in time to September 11th, 1984, 53 1 doesn't it? 2 A. I would have to look at this, if I may. You are 3 showing me a large part. 4 Q. Yeah. But I've shown it to you before, haven't 5 I, Doctor Wernicke? 6 A. Well, let me quickly look over it. Actually, I 7 don't remember seeing this. You may have shown me this, but 8 I've seen a lot of documents and I would have to look at this 9 in some detail to put this into context. 10 Q. Okay. Well, why don't you -- of course it's got 11 Weber Exhibit 4 there, who was the director of the German 12 medical component, wasn't he not? 13 A. Yes. 14 Q. And you are copied on this document, aren't you? 15 A. Yes. 16 Q. You're the last name there, aren't you? 17 A. Yes. 18 Q. In September of '84, you had been with Eli Lilly 19 and Company six months? 20 A. I joined in June so... 21 Q. Four months? 22 A. Four months. 23 Q. All right. Turn with me -- this is the -- it 24 says, "Attached please find the draft of the enclosures which 25 have been made, prepared in Bad Homburg." Correct, sir? 54 1 A. Yes. 2 Q. And the subject of this is draft of the reply to 3 the list of concerns; correct, sir? 4 A. Yes. 5 Q. And you knew about this list of concerns raised 6 by the BGA, didn't you? 7 A. Yes. I helped draft a response to those. 8 Q. You helped draft a response to the BGA; correct? 9 A. Yes. 10 Q. And you say you filed that with the FDA; 11 correct? 12 A. Yes. 13 Q. And that's that two-volume submission there? 14 A. I believe that is correct. 15 MR. McGOLDRICK: Your Honor, may I approach the 16 bench for just a minute? 17 (BENCH DISCUSSION) 18 MR. McGOLDRICK: Judge, I want to object only to 19 this extent. Of course, Mr. Smith should be allowed to 20 approach the Witness with a document that the Witness doesn't 21 have and show it to him, but I'm not sure that he should stand 22 in the witness box and hover over him and question him. 23 JUDGE POTTER: Do you have an extra copy of 24 that? 25 MR. SMITH: I'll see. 55 1 (BENCH DISCUSSION CONCLUDED) 2 Q. So I can get out of your face -- that's a Texas 3 phrase, isn't it, get out of your face, get out of my face? 4 A. I think so. 5 Q. Turn with me, Doctor Wernicke, to the last page 6 of Exhibit 64, and if we took a look at the next-to-the-last 7 page, we see that this is part of summarizing an opinion, 8 doesn't it? 9 A. Yes, it says that. 10 Q. The last paragraph of the last page of this 11 response to the list of concerns of the BGA says, quote, and 12 this is Doctor Schenk speaking, is it not? 13 A. Well, it appears to be, but remember I haven't 14 looked at this all recently. It looks like it is. 15 Q. Take my word for it. We've talked to Doctor 16 Weber. "If the drug is used according to the revised package 17 literature, that is, in agitated and suicidal patients only 18 together with concomitant sedative drugs, there should be no 19 doubt on fluoxetine's positive benefit/risk ratio in the 20 treatment of depression." Right, sir? 21 A. That's what this says, yes. 22 Q. Did you tell the FDA that Doctor Schenk had 23 concluded actually five years to the day before Joe Wesbecker 24 went to see Doctor Coleman and Doctor Coleman discontinued 25 Prozac because of his deterioration, did you tell the FDA that 56 1 it was Doctor Schenk's opinion and Lilly in Germany's opinion 2 that this drug would be beneficial and have a positive 3 benefit/risk ratio only if in agitated and suicidal patients 4 it was used together with concomitant medications? 5 A. I'd like to point out that this memo -- 6 Q. I think I can ask you to answer with yes or no 7 to the question, Doctor Wernicke. 8 A. I did not personally tell that to the FDA. 9 Q. Did you ever send this document to the FDA? 10 A. I did not have this document because I am only 11 one of the ccs on the cover memo. It clearly indicates that 12 the attachments were only sent to Doctor Zerbe. I don't 13 remember seeing this entire document except perhaps during the 14 depositions, so I cannot speak to whether and why and how this 15 was sent to the FDA. 16 Q. Okay. Is it your position here that this was 17 submitted to the Food and Drug Administration? 18 A. I don't have a position on that because I just 19 don't know. 20 Q. You are copied with this, aren't you? 21 A. On the cover memo, yes. 22 Q. And you were the one that was primarily 23 responsible for drafting this submission to the BGA? 24 A. The questions to the answers I was largely 25 involved in drafting. 57 1 Q. Did you -- and you're telling this jury you 2 never saw this? 3 A. I am telling you that I don't remember seeing 4 this whole document the way -- certainly not at the time that 5 I was working there. 6 Q. Do you remember seeing the summary of the 7 document? 8 A. No, I don't. 9 Q. Have you looked in here to confirm that in the 10 response -- this response that you sent to the BGA that was 11 two years later sent to the FDA, did you ever look in here to 12 see if that language is contained in here? 13 A. Well, no, because I didn't have this language. 14 Q. Nobody ever told you that it was Germany's 15 conclusion -- Lilly-Germany's conclusion -- not the BGA's 16 conclusion but Doctor Schenk with Lilly in Germany's 17 conclusion that this drug would be safe only if used with 18 concomitant sedatives in patients who were agitated and 19 present a risk of suicide? 20 A. You used both of those together, Doctor Schenk's 21 conclusion and Lilly-Germany. Now, it is true that Doctor 22 Schenk worked at the German affiliate and those may have been 23 at the time at one point their conclusion. I do know that the 24 BGA approved the drug and this is not the way it is in their 25 approval. 58 1 Q. It is, too. 2 A. I beg to differ, because what they say, as far 3 as I know -- I may have to look at the language -- but 4 concomitant medications may be necessary; that does not mean 5 that you need to or should or have to use those together. 6 Q. You're saying the difference is "should" versus 7 "may" -- Doctor Schenk says should and the German package 8 insert says may, and you think that's a distinction here, 9 Doctor Wernicke? 10 A. I think that is a fairly big distinction, yes, 11 from a clinical standpoint, certainly another factor. 12 Q. We people here in the United States don't get 13 the benefit of either one of those recommendations, either 14 "should" or "may." It doesn't say anything in the U. S. 15 package insert, does it, sir, about the use of concomitant 16 medication in agitated patients or suicidal patients, does it? 17 A. That's correct. 18 Q. Did you ever discuss this question with Doctor 19 Zerbe of whether or not the benefit/risk ratio, which I 20 believe you said Friday was the ultimate issue in safety, 21 isn't it? 22 A. Yes, I would agree. 23 Q. Whether there's a positive benefit/risk ratio? 24 Didn't you say Friday that's the real issue; that's what we 25 want to know? I believe your term was, at the end of the day 59 1 we want to know whether or not this drug was safe and the way 2 we define it is whether or not it has a positive benefit/risk 3 ratio; right? 4 A. Yes. That's correct. 5 Q. And here Doctor Schenk, the person that was 6 responsible for Prozac in Germany with Lilly, says it's going 7 to have a positive benefit/risk ratio only if used together 8 with concomitant medications in patients who are agitated and 9 suicidal; right, sir? 10 A. I'm not sure that that's exactly what she says. 11 I don't read this as saying that it has to be used only in 12 conjunction with medication. She said, "If the drug is used 13 according to the revised package literature, i.e., in agitated 14 and suicidal patients only together with concomitant sedative 15 drugs, there should be no doubt on fluoxetine's positive 16 benefit/risk ratio in the treatment of depression." I don't 17 believe that to say that one has to use this drug in 18 conjunction with a sedative medication. 19 Q. Well, if you want to have not any doubt about 20 the positive benefit/risk ratio, that's what she's saying is 21 the way to assure that, isn't it? 22 A. In agitated and suicidal patients she feels, 23 apparently, and I would have to talk to her, that that is 24 something that one can consider, which I believe is expressed 25 in the German package insert. 60 1 Q. When you say that the Prozac was approved in 2 Germany, when Lilly's lawyer was questioning you, you didn't 3 point out that when it was approved in Germany the only way it 4 could be approved was with the language that concomitant 5 sedative medications should be used in cases of suicidality 6 and excitability; correct, sir? 7 MR. McGOLDRICK: If Your Honor, please, I don't 8 think that's an accurate characterization. 9 JUDGE POTTER: Well, the Doctor is familiar with 10 it; if it's not, he can correct it. 11 Go ahead, Mr. Smith. 12 A. I didn't point that out because that wasn't part 13 of the question. And I would also further not -- 14 Q. It's part of the truth, isn't it? 15 A. It is part of much information, but I would 16 actually want to look at the German package insert because I'm 17 just not sure the way you phrased it that's exactly the way 18 they said it. It may be. 19 MR. SMITH: We may as well introduce it into 20 evidence. Offer Exhibit 103, the German package insert at the 21 time Joseph Wesbecker shot the Plaintiffs in this case. 22 MR. McGOLDRICK: May we approach the bench, Your 23 Honor? 24 (BENCH DISCUSSION) 25 MR. McGOLDRICK: Judge, the date of this 61 1 document is 1992. I don't know that it's the same and I'm not 2 sure what the foundation is for this document. 3 MR. SMITH: He's saying he had to see -- 4 JUDGE POTTER: Let him finish, Mr. Smith. Where 5 do you see 1992? 6 MR. MYERS: Last page, Judge, lower left-hand 7 corner. 8 MR. SMITH: Actually, it was approved in 9 December 1989. 10 MR. McGOLDRICK: And Mr. Smith just got through 11 telling the jury that it was approved on the date Joseph 12 Wesbecker shot the Plaintiffs, and that's just wrong. 13 JUDGE POTTER: Well, we don't know whether it is 14 or not. Mr. Smith, why don't you correct your own exhibit to 15 be 1992. Objection is overruled. 16 MR. McGOLDRICK: May I ask for instruction that 17 Mr. Smith's statement with respect to this being the package 18 insert in effect on the date of Joseph Wesbecker's -- 19 MR. SMITH: I'll correct that. 20 (BENCH DISCUSSION CONCLUDED) 21 Q. Doctor Wernicke, I said this was the package 22 insert that was in effect at the time Mr. Wesbecker committed 23 this act. Actually this is dated March 16th, 1992, which was 24 a translation that we had made after this litigation began, 25 and I am fixing to follow up with you as to the proposed 62 1 package insert for Germany that Lilly was proposing at the 2 time this incident occurred, but as far as currently what the 3 German people have or at least what they had in 1992, does 4 this appear to be a correct copy of that package insert? 5 A. As far as I know. This is the patient insert, 6 by the way. But remember I was not there so I can't testify 7 this is exactly what anybody had in 1992. 8 MR. SMITH: We'd offer 103, Your Honor. 9 JUDGE POTTER: Be admitted. 10 Q. Now, you say this is the patient information? 11 A. Yes. It looks that way to me. 12 Q. We don't get that in the United States, do we? 13 A. No. 14 MR. McGOLDRICK: Judge, may I approach? 15 SHERIFF CECIL: (Hands document to jurors). 16 (BENCH DISCUSSION) 17 MR. McGOLDRICK: Judge, if the Court please, 18 patients don't receive warnings in the United States. The FDA 19 doesn't -- that's not -- just the way the FDA is structured. 20 My understanding from Mr. Myers is that this was not to be 21 mentioned in this trial and here it's mentioned. I object. 22 MR. MYERS: Your Honor, just factually when we 23 went through a number of the depositions of Lilly employees, 24 specifically the German people, I expressed a concern and the 25 Court ruled out some of the testimony about warnings going to 63 1 patients for this very reason, that there's no issue in this 2 case that the patient should have been warned; the question is 3 whether or not the doctor should have been warned. 4 MR. SMITH: I said patients don't get this. 5 MR. McGOLDRICK: It puts that in issue. There's 6 no need to say it. 7 JUDGE POTTER: As I understand, Mr. Smith, the 8 reason you're admitting this is that the German government 9 conclusively came to a different conclusion than the American 10 government? 11 MR. SMITH: Yes. 12 JUDGE POTTER: Okay. I'm going to overrule the 13 objection. 14 (BENCH DISCUSSION CONCLUDED) 15 Q. Doctor Wernicke, turn with me to Page 2 of this 16 exhibit. 17 A. Okay. 18 Q. Under Risk Patients. Do you see it? 19 A. Yes. 20 Q. It says, "Risk of Suicide"? 21 A. Yes. 22 Q. Fluctin, and that's Prozac in Germany, isn't it? 23 A. Yes. 24 Q. It says, "Fluctin does not have a general 25 sedative effect on the central nervous system; therefore, for 64 1 his/her own safety, the patient must be sufficiently observed 2 until the antidepressant effect of Fluctin sets in. Taking an 3 additional sedative may be necessary. This also applies in 4 cases of extreme sleep disturbances or excitability." 5 Correct, sir? 6 A. Yes. 7 Q. That's what the German government approved 8 Prozac on in Germany; right? 9 A. I believe so. 10 Q. With that language? 11 A. I believe so, if this is a true translation, 12 yes. 13 Q. That language is not contained in the United 14 States packaging instruction, is it? 15 A. Not the same words. I know there is a 16 discussion of suicide and that patients have to be monitored 17 very carefully, that suicide is a risk for depression. 18 Q. And it doesn't say, though, that patients taking 19 an additional sedative may be necessary for these types of 20 patients, does it? 21 A. Not to my knowledge, no. 22 Q. And it doesn't say this also applies in cases of 23 extreme sleep disturbances or excitability, does it? 24 A. That's correct. 25 Q. You have relatives in Germany, don't you, still? 65 1 A. Yes, I do. 2 Q. They're getting different information, the 3 doctors there are getting different information about the risk 4 involved in this product than we are here in the United 5 States, aren't they, sir? 6 A. I would not agree with that, because this does 7 not speak to the risk of the product. What this speaks to is 8 how patients, like this, perhaps should be treated. That's 9 far different than the risk of the product. In fact, the 10 German government has exactly the same information as the 11 U. S. government. 12 Q. Isn't it talking about how this product can be 13 used in the safest way, Doctor Wernicke, in patients who were 14 most susceptible to the most horrible types of side effects in 15 connection with this drug? Isn't that what it's talking 16 about? 17 A. I don't think I would be that firm that this is 18 exactly what it's talking about. I think what they're talking 19 about is the disease state, that this drug is not sedating, 20 and as a reflection that medical practice in Germany is a 21 little bit different than in the United States, and the 22 regulatory authorities apparently have a slightly different 23 view of what they should do. This is reflected in the way 24 this is written. 25 Q. Apparently Lilly employees in Germany, as early 66 1 as 1984, had a different view of how this drug should be used, 2 didn't they? 3 A. That seems to be reflected in some of the things 4 that they say. 5 Q. Especially in this response that Doctor Schenk 6 was making to the BGA; correct, sir? 7 A. Yes. I would say that Doctor Schenk considered 8 this as a possible issue, also. Remembering, however, that 9 she is a physician in Germany and she is used to their 10 regulatory background. 11 Q. Well, do you know if Doctor Schenk was doing 12 anything other than trying to give the right information to 13 people of her country in connection with the proper use and 14 the risk that this drug presents, Doctor Wernicke? 15 A. I think that's certainly one of the things that 16 she was doing. I don't see anything that suggests that she 17 herself thought that this was a particular risk. I believe 18 what she was responding to was what the German government 19 would want to see in their labeling, which is entirely 20 consistent with their approach to how labels are written. 21 Q. That's not what she says. She doesn't say, 22 "We'll agree that this is what the German government wants." 23 If you look again -- and I'm not trying to beat this to death, 24 Doctor Wernicke, but I think we had -- you had in 1984 some 25 serious, serious information about this serious side effect 67 1 with this drug and what she's saying here, is it not, if this 2 drug -- if this drug -- she's not talking about treatment, 3 she's talking about this drug, isn't she? 4 A. That's what she says in that paragraph. 5 Q. She says, "If this drug is used according to the 6 revised package literature, that is, in agitated and suicidal 7 patients only together with concomitant sedative drugs, there 8 should be no doubt on fluoxetine's positive benefit/risk ratio 9 in the treatment of depression." Right, sir? 10 A. That is what she says, but the way you started 11 the question I would disagree with that there was a serious 12 side effect. I don't remember your exact words, but you put 13 it in the context suggesting that she thought that there was a 14 serious safety issue with this drug, and that I do not agree 15 with because I've talked with Doctor Schenk many times in the 16 past. 17 Q. Did you ever talk to her about her feelings on 18 this? 19 A. We talked about the use of sedative medication. 20 We talked about the numbers in the analyses. We worked on a 21 lot of issues together. 22 Q. Then maybe you'd better tell this jury what you 23 said to Doctor Schenk about the use of concomitant medications 24 and her recommendation that this was the way to assure a 25 positive risk/benefit ratio in patients who were suicidal and 68 1 agitated. 2 A. I was never asked whether I thought this drug 3 should be used with concomitant medications in any type of 4 patients. Our discussion was what does the data show, what 5 information do we have. 6 Q. Did you ever tell her she's wrong -- 7 A. I don't remember. 8 Q. -- in this recommendation? 9 A. I don't remember that actually being her 10 recommendation. We talked about that concomitant drugs could 11 be given. I explained to her that we had data that showed 12 that it was given in a number of patients, and that was how 13 our discussions were carried out. 14 Q. Did you tell her, "Well, you need to change your 15 opinion here, Doctor Schenk, you're wrong?" 16 A. Remember, as I told you before, I had not seen 17 that entire document. If, in fact, that was her opinion she 18 did not express it in that way to me. 19 Q. She didn't tell you that in these discussions 20 that you had? 21 A. Not in the sense that she thought that we had to 22 give concomitant medications. 23 Q. Could you be mistaken on that like you were 24 mistaken on those unacceptable damaging effects that you were 25 confused about in Doctor Talbott's correspondence with the 69 1 United States Food and Drug Administration? 2 A. All I can remember is the conversations I had 3 with Doctor Schenk. I know we spent a lot of time looking at 4 a lot of the data. In answering the questions, I can't 5 specifically testify to every conversation I had with her, 6 which is now almost ten years ago. 7 Q. I don't know that the jury has in front of them 8 what actually was the recommended package labeling for Prozac 9 in Germany at the time this incident occurred, September 14, 10 1989. It's contained in Exhibit 102, Plaintiffs' Exhibit 102. 11 Let's go over it, and I just have one copy of it. 12 MR. McGOLDRICK: I'm sorry. Mr. Smith, if we 13 could approach the bench. 14 (BENCH DISCUSSION) 15 MR. McGOLDRICK: If Your Honor, please, I object 16 to -- it's the same objection I made before when Mr. Smith 17 talked the first time about how this was the package insert in 18 effect in Germany when Mr. Wesbecker did this incident. This 19 document was dated December 6, 1989. It's after the Wesbecker 20 incident. It's the second time he has said that, and I think 21 it's objectionable and I think the jury ought to be instructed 22 about that by the Court. 23 JUDGE POTTER: Was it within a couple of months 24 of it? 25 MR. McGOLDRICK: That's right. As long as you 70 1 let them know you weren't exact about those dates. 2 JUDGE POTTER: 102 is in. We don't know if that 3 was in effect in September or not, all we know is that was -- 4 MR. McGOLDRICK: The drug wasn't approved, it 5 couldn't have been in effect, we do know that, Your Honor. 6 Mr. Smith is saying it's in effect on the date of -- 7 MR. SMITH: This is what was being recommended 8 as the German package insert. 9 JUDGE POTTER: Okay. 10 (BENCH DISCUSSION CONCLUDED) 11 Q. I'm going to get this right yet, Doctor 12 Wernicke. Actually Fluctin wasn't approved in Germany until 13 December -- late December 1989; isn't that right? 14 A. That's my understanding. 15 Q. Which was after this incident happened in 16 September of 1989; correct, sir? 17 A. Yes. 18 Q. And actually the German government still was not 19 sufficiently satisfied with the safety of this drug to approve 20 this product in Germany at the time that this incident 21 occurred; right, sir? 22 A. I don't know what their concerns were, if any, 23 at that time. I cannot suppose to look into the BGA's mind. 24 Q. In any event, the recommendation from Lilly to 25 the BGA in Germany at the time was contained in Exhibit 102. 71 1 Let me read this with you. It says, "Fluoxetine does not act 2 generally sedating..." Right, sir? 3 A. Yes. 4 Q. "...until the onset of the depressive 5 alleviating effect, the patients have to be observed 6 adequately. In patients with suicidal risk, continuous 7 observation and/or a generally sedating additional therapy can 8 be necessary. In patients suffering from agitation or marked 9 sleep disturbance, Fluctin has to be used with special care." 10 Doesn't it? 11 A. That's what it says. 12 Q. And that was the recommendation for use of 13 Prozac in Germany on September 11th when -- September 14th, 14 when this incident occurred; right, sir? 15 A. I thought you said it was approved after that. 16 I'm not certain of the date. If that's the package insert, 17 that would have come at the time of approval. 18 Q. Well, this is what Doctor Schulze-Solce had 19 presented from Lilly to the BGA to be used as their proposed 20 labeling? 21 A. I would presume that. I'm not quite sure. I 22 have to look at the whole document, but I will take your word 23 for that. 24 Q. All right. Doctor Wernicke, Exhibit 234 is Eli 25 Lilly and Company E-mail dated September 14th, 1989, at 13:56, 72 1 which is about five hours after Joseph Wesbecker committed his 2 act. Can you identify that as Lilly E-mail? 3 A. I don't remember seeing this. I would have to 4 look over it. I know I'm copied on it and apparently I was at 5 the meeting, but I would have to look at it to jog my memory 6 as to this meeting. 7 MR. SMITH: We'd offer 234, Your Honor. 8 JUDGE POTTER: Let him finish looking at it, Mr. 9 Smith, see if he has anything to say. 10 A. (Reviews document). 11 MR. McGOLDRICK: No objection, Your Honor. 12 JUDGE POTTER: Okay. Be admitted. 13 SHERIFF CECIL: (Hands document to jurors). 14 Q. Have you had an opportunity to review the 15 document, Doctor Wernicke? 16 A. Yes. 17 Q. Let me ask you this first: This document is 18 dated September 14th, 1989. That's the day this incident 19 occurred; correct, sir? 20 A. I presume that, as I remember. I don't know the 21 date exactly. 22 Q. The time as noted on Exhibit 234 is 13:56; 23 correct, sir? 24 A. Yes. 25 Q. That would be 1:56 in the afternoon in 73 1 Indianapolis, would it not, sir? 2 A. Yes. 3 Q. This would be then close to 2:00, so we're 4 talking about, about five hours after this incident occurred; 5 correct, sir? 6 A. Yes. 7 Q. Did you know this incident occurred -- had 8 occurred then? 9 A. I don't remember. This is the first time I 10 remember now seeing this memo, and I just can't remember that 11 day in 1989, whether I knew about this incident. 12 Q. We can talk about that. It says that this 13 document is addressed to Doctor Charles M. Beasley; right, 14 sir? 15 A. Yes. 16 Q. He is a psychiatrist at Eli Lilly, is he not? 17 A. Yes. 18 Q. Beverly Fry; correct, sir? 19 A. Yes. 20 Q. She is a systems analyst? 21 A. I believe so. 22 Q. John H. Heiligenstein is a psychiatrist at 23 Lilly? 24 A. Yes. 25 Q. Beth Meloy is who? 74 1 A. She was a group manager of some of the clinical 2 research associates, I believe, I'm not exactly sure what her 3 role was at that time. 4 Q. She's a clinical research associate group 5 manager? 6 A. I believe so. I don't remember exactly what her 7 role was at that time. 8 Q. And clinical research associates are those 9 people at Lilly who help the research physicians in 10 administration of the Lilly clinical trial; correct, sir? 11 A. Yes. 12 Q. And additionally help the research physicians at 13 Lilly in investigating adverse events in connection with the 14 drug; correct, sir? 15 A. That's right. 16 Q. You're listed and then Doctor David Wheadon is 17 listed; correct? 18 A. Yes. 19 Q. And Doctor David Wheadon was at that time a 20 psychiatrist who is a clinical research physician; right? 21 A. Yes. 22 Q. The subject of this meeting five hours after 23 this occurred here in Louisville is mortality in the Prozac 24 depression database; right, sir? 25 A. Yes. 75 1 Q. Now, mortality means death, doesn't it? 2 A. Yes. 3 Q. That could be death by suicide? 4 A. Yes. 5 Q. Homicide? 6 A. Yes. 7 Q. Overdose? 8 A. Yes. 9 Q. Or other causes? 10 A. Yes. 11 Q. It says in attendance Bev Fry -- that's the 12 systems lady; right? 13 A. Yes. 14 Q. Charles Beasley, that's the Lilly psychiatrist; 15 right, sir? 16 A. Yes. 17 Q. Yourself, you are the Lilly Prozac clinical 18 monitor and research physician at the time, are you not? 19 A. I'm not sure whether I was the primary monitor 20 at that time because that role changed over time. 21 Q. You were still intimately involved with Prozac 22 on September 14th, 1989, weren't you, Doctor Wernicke? 23 A. Yes. Somewhat. Less so than before, but I was 24 still involved. 25 Q. And Bruce Dornseif; right? 76 1 A. Yes. 2 Q. Bruce Dornseif authored this document, did he 3 not? 4 A. Yes. 5 Q. And he is one of the top Eli Lilly and Company 6 statisticians, is he not? 7 A. He's a Ph.D. statistician, one among many. He 8 was assigned to this project. 9 Q. He had been a statistician in connection with 10 Prozac for quite some time, had he not? 11 A. Yes. 12 Q. Let's read it together. It says, "All attendees 13 were in agreement as to the importance of Medical being able 14 to proactively provide information as to whatever source, FDA, 15 consumer groups, et cetera, on adverse events as well as 16 mortality in the clinical trial database." Right, sir? 17 A. Yes. 18 Q. You're in Medical and Doctor Beasley's in 19 Medical at the time; right? 20 A. Yes. 21 Q. You said you-all were all in agreement that it's 22 important that you be able to proactively provide information; 23 right, sir? 24 A. Yes. 25 Q. What does proactively mean, Doctor Wernicke? 77 1 A. To have the information available before 2 somebody asks for it. 3 Q. Have it at hand, be in the forefront with this 4 information? 5 A. To have it available is what that means to me. 6 Q. Proactive, to be in the forefront, to be there 7 early, to have this already in hand; right, sir? 8 A. You could look at it that way, yes. 9 Q. It says, "All attendees were in agreement as to 10 the importance of Medical being able to proactively provide 11 information to whatever source, FDA, consumer groups on 12 adverse events as well as mortality data in the clinical trial 13 database." Now, I thought you testified earlier, Doctor 14 Wernicke, that the FDA had all this information on mortality 15 in connection with Prozac, didn't they? 16 A. Yes. 17 Q. Didn't you testify to that? 18 A. I testified to that, yes. 19 Q. Why was there then at this time, five hours 20 after this event occurred, a need to proactively provide 21 information? 22 A. Because as every moment passes, new information 23 comes in. If we -- excuse me. If we made a submission 24 yesterday to the FDA, that data would be at least several 25 hours, more likely several days old. So as information comes 78 1 in all the time, it's never current by definition. If a new 2 event happens, you have to look at it again. So, yes, we 3 submit it all and in due time everything was submitted, but 4 that's never -- it can't ever be up to date if you have an 5 active system. 6 Q. What was new here was, in fact, Doctor Wernicke, 7 you had just learned that Joseph Wesbecker was on Prozac and 8 had committed this act, hadn't you? 9 A. I do not remember that in conjunction with this 10 meeting. I don't remember this meeting exactly. That may 11 well be, but I don't remember whether that's the case. 12 Q. It may well be that you-all were having a 13 meeting about this five hours after it happened, mightn't it, 14 sir? 15 A. That could well be. 16 Q. And you knew that you were going to get some 17 inquiries from the FDA and consumer groups about this, didn't 18 you, sir? 19 A. If this meeting was in conjunction with that and 20 if I knew that then I would have supposed that but, as I said, 21 I don't remember when I learned that Mr. Wesbecker was taking 22 Prozac, and I don't know about the relationship of that to 23 this meeting. 24 Q. But there wouldn't have been any other reason to 25 do all of this had you not just learned about it; right? 79 1 A. I would disagree with that completely. 2 Q. Then why was there a need all of a sudden to 3 proactively provide this information, Doctor Wernicke? 4 A. We had many different things going on. This is 5 one memo about one meeting. This could have been in context 6 to aplastic anemia in Ireland. I don't know. Anytime 7 anything happened, we got together and decided how we were 8 going to answer those questions. And it may well be this was 9 in relationship to that, but I can't say that. 10 Q. It doesn't say that the subject of this was 11 aplastic anemia in Ireland, does it, Doctor Wernicke? 12 A. No. And it also doesn't say that this is in 13 conjunction with suicide or homicide within relationship to 14 fluoxetine. 15 Q. Well, it talks about death and mortality, 16 doesn't it? 17 A. Yes, which can happen from aplastic anemia or 18 anything else. Actually, I would be surprised that if this 19 were strictly in relationship to Mr. Wesbecker's acts that 20 that should be mentioned; that there should be a focus on 21 suicidality and homicides. That's why I'm not at all 22 convinced that this is in relationship to this case. 23 Q. Let's go ahead and look at the rest of it; maybe 24 we can pick up some better hints as we go through. Again, is 25 it your testimony, Doctor Wernicke, that it could well be that 80 1 you people at Lilly learned about this five hours after this 2 happened and had a meeting about the data that you had in your 3 database? 4 A. That's entirely possible. 5 Q. All right. It says, "With regard to adverse 6 events -- and I'm reading now from the second full paragraph 7 of the first -- second full sentence in the second full 8 paragraph. "With regard to adverse events, Joe was 9 confident" -- that's you. 10 A. Yes. 11 Q. "...Joe was confident that the fluoxetine safety 12 update was a reliable and accurate source that could be 13 immediately tapped without reinventing the wheel;" right, sir? 14 A. Yes. 15 Q. Does that help you? 16 A. No. 17 Q. All right. Let's read on. It says, "On the 18 downside, Bev stated" -- that's your system person; right? 19 A. Yes. 20 Q. "On the downside, Bev stated that to develop a 21 global fluoxetine database would require no less than a 22 complete conversion of the U. S. fluoxetine database to 23 standards." Right, sir? 24 A. Yes. 25 Q. That tells me, Doctor Wernicke, that the U. S. 81 1 fluoxetine database was not up to standards or was below 2 standards. 3 A. That may tell you that, but that is not what 4 this means. 5 Q. All I can do is read what's written here in 6 English. 7 A. Yes. But I know what they're talking about and 8 I will be glad to explain that. 9 Q. Why don't you tell us what it was that was going 10 to cause a complete conversion of your database to make it up 11 to standards. 12 A. What that means was when we go back, and I don't 13 remember what context I talked about this with, we had the 14 U. S. database and that was computerized and we had -- that 15 was what we largely used with the pivotal studies for the FDA 16 and foreign regulatory authorities. As time went by, more and 17 more studies were being done outside the U. S. and those were 18 not in the U.S. database. The reference to standards was an 19 attempt to unify, to make a global database, and, in fact, I 20 was on a committee that worked for a number of years in 21 defining standards and unifying all studies so that everything 22 could go into a standard database. And that's what standards 23 means here, that to convert -- and that system was being 24 developed at that time. I don't know its exact status, but 25 what this refers to is merging all the clinical trials 82 1 worldwide into one database, which is a very large, difficult 2 process. 3 Q. What it says, Doctor Wernicke, it says, "On the 4 downside, Bev stated that to develop a global fluoxetine 5 database would require no less than a complete conversion of 6 the U. S. fluoxetine database to standards." She's talking 7 about the U. S. fluoxetine database having to be converted to 8 standards? 9 A. To the standardized worldwide database, that's 10 correct, because that apparently had not been done at that 11 time. 12 Q. In connection with this incident it's being 13 discussed that we better do it; right, sir? 14 A. What she's saying that if we wanted to do that, 15 that would take a lot of time. 16 Q. It says, "Bev will provide me next week with an 17 estimate of the time and resources that such an undertaking 18 will require." Right, sir? 19 A. Yes. 20 Q. It says, "The clinical scientists made up a 21 proposal as to how best to ascertain mortality in the U. S. 22 clinical trial database." Right, sir? 23 A. Yes. 24 Q. Now, the inference here is, is that you didn't 25 know what mortality was in the U. S. clinical trial database 83 1 at that time, if you were trying to -- if you were making 2 proposals about how to ascertain what it was. 3 A. At that moment at 13:56 on that day we did not 4 have the exact number and, as I've explained, that number 5 changes constantly. 6 Q. But you're supposed to have something in place 7 that captures it. 8 A. Yes. We have it in place to capture it, but the 9 answer does not appear on a screen that constantly changes as 10 you walk by. You have to ask the question and you have to do 11 the calculations and the analysis. 12 Q. Well, is it your testimony that you heard about 13 this incident, you guys up here at Lilly got together with the 14 statisticians and with the computer people and said, "Gosh, we 15 don't know how many people have been killed. We don't know 16 how much mortality there is in our U. S. clinical trial 17 database." Is that what you're telling this jury? 18 A. As I explained before, I do not know whether 19 this meeting was in relationship to this event. So when you 20 say that you guys heard about this event and then you had this 21 meeting, I can't testify to that. 22 Q. I am trying to help your recollection, sir. 23 A. It doesn't help because I don't remember whether 24 this in relationship to that. It may well have been, but I 25 just don't know. 84 1 Q. You then give two proposals. You say, "One, 2 look only at controlled double-blind trials across all 3 indications in which fluoxetine and placebo were both 4 represented. Mortality rates would be obtained for fluoxetine 5 and placebo on a per-patient basis." Right, sir? 6 A. Yes. 7 Q. Hadn't this been done up to this time, Doctor 8 Wernicke? 9 A. It was done sometime in the past but, again, if 10 there was one more event and you don't know that until you go 11 and look. 12 Q. Why didn't you start with going and looking at 13 what information you had in the past? Why are you having to 14 do something different? Why are you having to, as Doctor 15 Dornseif says, or you said, reinvent the wheel? 16 A. That just means redo all the major analyses. We 17 had the DEN database, which is a 1639 system that we could 18 look at at any time, but to recalculate the numbers and the 19 rates, this involves a much more careful calculation, as I 20 explained on the easel. 21 Q. We're going to talk about that later. Don't 22 worry. But at this time you guys were worried, you needed to 23 get your statistics in order, didn't you? You needed to look 24 at several ways to look at mortality in your database; that's 25 what you were searching for, wasn't it? 85 1 A. We were discussing how to best analyze and 2 present the information, recognizing that there are many 3 different ways that one can do it. 4 Q. And this is five hours after this happens that 5 you-all are talking about how can we look at deaths that occur 6 in our clinical trials; right, sir? 7 A. Yes. All deaths. 8 Q. The second way that you proposed was, "To obtain 9 mortality rates for Prozac, placebo and comparitors for all 10 types of fluoxetine trials, double-blind, open label and 11 compassionate use, across all indications. Mortality rates 12 would be provided on an exposure time basis, number of deaths 13 per patient years." Right, sir? 14 A. Yes. 15 Q. Did you ever do Item One, Doctor Wernicke? 16 A. I don't remember. 17 Q. Did you ever do Item Two, Doctor Wernicke? 18 A. I don't remember that, either. And the reason I 19 don't is because I was involved in this largely because of my 20 experience with the safety update. I don't expect that I 21 would have been the person to do that analysis primarily; I 22 suspect Doctor Beasley would have done that. 23 Q. Would you have seen it, sir? 24 A. I think I probably would have seen it, but I 25 don't remember the numbers. 86 1 Q. And you've never seen it in any one of these 2 analyses, did you? 3 A. I don't remember seeing any one of these 4 analyses, I can't say whether I did or did not. 5 Q. Don't you think that would be something you 6 would remember, Doctor Wernicke, about deaths that occurred in 7 people taking Prozac? 8 A. We had many things going on and there had been a 9 number of deaths all along. I'm not sure this is anything 10 more than -- a look for some reason at things that were going 11 on. I just don't know. 12 Q. You don't know. You had a number of deaths all 13 along but you hadn't analyzed your database to know what 14 number of data -- what number of deaths you had and how to 15 analyze the statistics on those deaths; is that what you're 16 telling this jury? 17 A. We had analyzed the statistics and the events 18 but, as I explained before, new ones come in and there's 19 really not a question of how to do it. It's not how do we 20 apply statistics; it's a question of what data sets do we look 21 at, controlled studies, open studies. We know that if one 22 wants to make a comparison, one has to use controlled studies. 23 That's what this speaks to. 24 Q. But you hadn't done that before? 25 A. Yes. But as I've said several times, new events 87 1 could occur. If we wanted to do it currently, we'd have to do 2 it again. 3 Q. When would have been the last time that you had 4 had an analyzed mortality in the Prozac clinical trials before 5 September 14th, 1989, Doctor Wernicke? 6 A. Well, certainly at the time of approval. 7 Q. Okay. That would have been December 1987? 8 A. Yes. 9 Q. All right. Had you done it after that? 10 MR. McGOLDRICK: Excuse me. I think that was 11 misstated. 12 MS. ZETTLER: December 1985. 13 MR. SMITH: That's when it was approved. 14 December 1987? 15 MR. McGOLDRICK: I thought you said '-6. I 16 apologize. 17 Q. When after December 1987 did you analyze deaths 18 in people taking Prozac? 19 A. I don't personally remember being involved in an 20 analysis. 21 Q. I thought you were responsible for the safety of 22 Prozac and intimately involved in it, sir. 23 A. As I've testified and told you even today, that 24 as time went by, my responsibilities shifted to a number of 25 other projects, and some of the psychiatrists took over more 88 1 and more of the fluoxetine, Prozac, work. 2 Q. Now you're not as responsible? 3 A. There was a transition that I've described 4 before and, yes, I still had a lot of responsibility, but I 5 was not involved in a lot of the day-to-day activities. 6 Q. Who was most responsible for this drug and the 7 safety of this drug in September 1989, Doctor Wernicke? 8 A. That is very difficult for me to say. From this 9 memo, it would look like certainly Doctor Charles Beasley 10 would be very heavily involved in that. 11 Q. Well, is Doctor Charles Beasley, on 12 September 14th, 1989, the person that knew most about the 13 safety at Lilly in connection with Prozac? Is that your 14 testimony here? 15 A. I'm not sure that I can speak to who knew the 16 most. There were a lot of people involved, a lot of people 17 knew a lot of things. So I don't want to venture to say who 18 knew the most. 19 Q. Certainly you had been there longer than Doctor 20 Beasley had, hadn't you? 21 A. Yes. 22 Q. Much longer than Doctor Beasley had? 23 A. Several years. 24 Q. You had been there longer than Doctor 25 Heiligenstein, hadn't you, sir? 89 1 A. Yes. 2 Q. You had been there longer than some of these 3 other gentlemen that are mentioned here, Doctor David Wheadon? 4 A. Yes. 5 Q. The three psychiatrists that were on board at 6 the time? 7 A. Yes. 8 Q. You were senior in service to them; is that 9 right? 10 A. Yes. That's right. 11 Q. Now, are you telling this jury that on September 12 14th, 1989, they knew more about the safety of Prozac than you 13 did? 14 A. I can't say exactly who knew what at what time. 15 Certainly what they knew, but I can say that they were very 16 much involved in the day-to-day analyses and the monitoring of 17 the drug. 18 Q. Weren't you? 19 A. I was to some extent, but I don't know exactly 20 what point we were at in the transition. 21 Q. Well, how long did you stay at Lilly? 22 A. Until '89, end of '89. 23 Q. All right. Certainly you were at this meeting, 24 weren't you? 25 A. Yes. 90 1 Q. With Doctor Beasley, weren't you? 2 A. Yes. 3 Q. Representing the medical component, weren't you? 4 A. Well, when you say representing the medical 5 component, all of us were in the medical component. 6 Q. Not Mr. Dornseif or Ms. Fry? 7 A. Oh, yes. They were a part of the medical 8 system. They weren't physicians, but they were in the medical 9 group. 10 Q. Okay. Then we're going to be picky. You and 11 Doctor Beasley were the two M.D.s there, weren't you? 12 A. Yes. 13 Q. Now, when had you last looked at deaths in the 14 Prozac clinical trials or in deaths occurring postmarketing 15 before September 14th, 1989? I think that was my original 16 question. 17 A. When you say "you" I take that to mean me 18 personally, not the company? 19 Q. I'm interested in what you know and what the 20 people -- what you know about what was occurring in the 21 company, since you were employed there, sir, and I wasn't. 22 A. When I personally was involved -- when I was 23 very actively involved was up to the time of approval. After 24 that time, the other physicians, specifically, the 25 psychiatrists took over more and more and they handled more of 91 1 the analyses. This was several -- actually just a few months 2 before I left, and I know by that time that my role in the 3 fluoxetine development was basically as an adviser and because 4 of my knowledge of the safety update and the preapproval 5 process. 6 Q. Do you know when the last analysis had been made 7 of deaths in the Prozac database before Joseph Wesbecker did 8 this on September 14th, 1989? 9 A. No, I do not. 10 Q. Would it be when these PADER things are filed 11 that are in red on this time line? 12 A. Well, that would not be an analysis of the 13 clinical trial database; those were spontaneous reports. 14 Q. When was there ever an analysis of deaths in the 15 Prozac clinical trials or postmarketing before September 14th, 16 1989, and after this drug went on the market in December of 17 1987? 18 A. The only thing that I can personally testify to 19 is what I did in conjunction with the safety update and the 20 approval process. 21 Q. I want to know what you know, whether you did it 22 or not, and I suspect everybody here wants to know what you 23 know. You've been telling us about baseball games; you've 24 been telling us about statistics; you've been telling us a lot 25 of things here. Now, I think it's important that you let us 92 1 know what happened, what analyses were made between December 2 1987 and September 4th, 1989, when this happened concerning 3 deaths while people were using Prozac. 4 A. What I know is that periodic reports or the 5 PADER reports that you mentioned were submitted, those numbers 6 were analyzed. I am not aware of another analysis on the 7 clinical trial database specifically dealing with deaths. If 8 that was done, I was not specifically involved and certainly 9 don't have any memory of it. 10 Q. So whether or not people were becoming violent 11 and aggressive and killing people or whether or not people 12 were becoming agitated and committing suicide or agitated and 13 committing homicides just hadn't been analyzed from the time 14 the drug went on the market up until the time this happened; 15 is that what you're saying? 16 A. That is not my testimony. I have said that I 17 was not personally involved in any such analysis. What I do 18 know is that periodic reports were made to the FDA. 19 Q. Who was doing that? 20 A. The periodic reports were processed through the 21 clinical group and sent from Doctor Talbott's office. 22 Q. You were in the clinical group, then, weren't 23 you? 24 A. Yes. But at that time I was not primarily 25 involved with fluoxetine, as I've said many times before. 93 1 Q. Was Doctor Beasley? 2 A. He was involved as well as Doctor Wheadon and 3 Doctor Heiligenstein. 4 Q. But you were at this meeting. You had to have 5 been at this meeting for a purpose. 6 A. Yes. And I know what that purpose was. 7 Q. And you made suggestions there? 8 A. Yes. 9 Q. Do you remember now that this meeting was in 10 fact in connection with what did in fact occur on September 11 14th here in Louisville, Kentucky? 12 A. No, I'm sorry. I don't remember this meeting at 13 all, and if you hadn't shown me this memo I would not have 14 remembered a meeting about this specific issue. In fact, I 15 don't remember going to this meeting, but obviously I did. 16 And the other part of the question was why was I at this 17 meeting, and it clearly is indicated it's because of my 18 experience with the safety update and to make sure of the 19 clinical trial database. 20 Q. You thought that the safety update would be 21 sufficient to give any answers, didn't you? 22 A. To look at comparative rates. 23 Q. But there was all of a sudden going to be a 24 serious look taken in several different ways at deaths that 25 occurred during the clinical trials and I assume 94 1 postmarketing; is that right? 2 A. Yes. And that's quite appropriate, yes. 3 Q. But it hadn't been done up to this point, had 4 it? 5 A. As I said several times before, I don't remember 6 any analysis. I suspect if there were a more recent 7 comprehensive analysis that would have come up, but I just 8 don't know. 9 Q. Well, there obviously hadn't been any analysis 10 as mentioned here in Points One and Two or it wouldn't have 11 been suggested as strategy. 12 A. Well, it could have been done a month before. 13 As I explained before, events happen, time passes. If you 14 want to say what is the current situation today, you can't 15 depend on an analysis that was done three months ago, even 16 three weeks ago. 17 Q. If it had been done a month before, don't you 18 think somebody would have mentioned and you would have 19 mentioned, "Wait a minute, we don't know to do this. We did 20 it a month before"? 21 A. Well, if it's a very important question, let's 22 take, for instance, bone marrow failure or aplastic anemia. 23 Let me explain how and why we do this. We had in Europe many 24 studies ongoing. There are thousands of patients on the drug 25 and we could at any moment get other reports of any event. If 95 1 we say, well, this was done three months ago and said let's 2 just not look at anything and it turned out it happened to be 3 three cases of aplastic anemia that came in this morning, that 4 would be entirely inappropriate to just say, well, we're going 5 to use some dated analysis. 6 Q. You're talking about reinventing the wheel, 7 you're talking about two sophisticated ways to look at your 8 database. Your database is something that's an electronic 9 database, isn't it? 10 A. For the U. S. it was. 11 Q. And Doctor Leigh Thompson, your chief scientific 12 officer, has said that your database is the best database in 13 the world, that other companies are coming in and the FDA is 14 proud of your database. You're telling me that you couldn't 15 just touch up the database and get this information, and that 16 it in fact wasn't being provided on a daily basis? 17 A. Yes. I am telling you that, because in fact a 18 lot of people think that that can be done. As you see here -- 19 and even without this issue of making it all into this unified 20 worldwide database -- it's not that simple. There isn't a 21 button on the computer that says answer and you push that. A 22 lot of people that aren't involved have that view, but it's 23 really much, much more complicated. 24 Q. I would think that you would know at Eli Lilly 25 and Company if people were dying when they were using your 96 1 drug, I would think you would know it and I think you would 2 know it on a regular basis. Is it your testimony that you 3 didn't know that on September 14th? 4 A. My testimony is that we had access to all the 5 spontaneous and 1639 reports that can be pulled up on an 6 instantaneous basis. To look at comparative rates, one has to 7 put in all the data that's available and redo all of those 8 calculations. 9 Q. So that's what you were doing when you got word 10 of this, you were doing recalculations? 11 A. We were bringing the database up to date and, as 12 I testified before, that as you heard of this -- and if I hear 13 that again I'm not going to be able to answer your question 14 because it always supposes that I knew about that and I 15 testified that I did not and I do not remember that. 16 Q. Maybe it will be a little help to look at the 17 next-to-the-last paragraph here. It says, "Bev estimates that 18 Systems could have the first cut completed by October 2nd, and 19 the second cut completed by October 13th." Right? 20 A. Yes. 21 Q. "The ancillary information as outlined in the 22 preceding paragraph" -- and I forgot that, that's talking 23 about details and particulars in connection with the deaths; 24 right? 25 A. Yes. 97 1 Q. And one of the details that you-all were going 2 to pull up was the use of concomitant medications in these 3 people that died, wasn't it? 4 A. Let me see if they mention that. I don't see 5 that in that previous paragraph: age, sex, drug maintenance, 6 dose, dose at time of death, type of drug, reason for death. 7 PIP means patients. Oh, yeah. I'm sorry. Concomitant 8 medications, yes, current chronic illness, admission, regular 9 events. 10 Q. So you want to get some information on 11 concomitant medications; right? 12 A. Presumably, yes. 13 Q. And you're going to get concomitant medications 14 over all your trials, aren't you, in connection with death? 15 A. To bring those up to date it will take it looks 16 like quite awhile, almost a month to bring that whole 17 worldwide database up to current levels. 18 Q. It says, "The ancillary information as outlined 19 in the preceding paragraph would be provided by October 2nd." 20 Right? 21 A. 20th. 22 Q. 20th. "Charles indicated that these results 23 would be used in a PR document developed by a person or 24 persons unknown at this time." 25 A. That's what it says here, yes. 98 1 Q. So all this stuff that you're doing is going to 2 be turned into a public relations document? 3 A. That is what Bruce Dornseif said Charles said. 4 I'm not sure I would presume from that that that's actually 5 what happened. This is not company policy and I don't know 6 that this is the way it worked out. 7 Q. It certainly isn't -- it looks like it's going 8 to be company policy to turn this information into a public 9 relations document, doesn't it? 10 A. My view of the way this is handled and my 11 involvement in this is before and this is to now is that I 12 analyze the data, I provide the answers. If people want to 13 use it, then I hand it over and then how people use it, that's 14 up to them. As far as I know, it's accurate and correct. 15 Q. Had you ever done anything in preparing a public 16 relations document before September 14th, 1989, Doctor 17 Wernicke, while you were at Lilly? 18 A. If in the context of that you will include 19 things like annual reports, which I presume would fall into 20 that category, I certainly provided data and information. 21 Q. Did you ever provide data on deaths like this 22 that was going to be turned into a public relations document? 23 A. I don't remember providing data specifically for 24 that. I don't -- actually, I consider it irrelevant why 25 people want it. If it's a legitimate question and it comes 99 1 from somebody that should have access to that information, I 2 provide it to the best of my ability and then it's their 3 responsibility to use it in a manner they deem appropriate. 4 Q. See, it looks like, though, in this first 5 paragraph that you said, "All attendees were in agreement as 6 to the importance of Medical being able to proactively provide 7 information to whatever source, FDA, consumer groups." Then 8 down in the next-to-the-last paragraph after you've discussed 9 all of these different ways you can look at death, you discuss 10 it's going to be turned into a public relations document? 11 A. We did not discuss that. What it says is 12 "Charles indicated that these results would be used in a PR 13 document." That's apparently his opinion. As I said, I don't 14 remember this meeting, why he said that, what exactly the 15 question was. 16 Q. Do you remember talking to Doctor Beasley about 17 this? 18 A. No, I don't, not this particular issue. 19 Q. Do you remember, have you had an opportunity to 20 talk with Doctor Beasley at all since you've left Lilly? 21 A. Yes. I've chatted with him several times. 22 Q. Have you ever mentioned this to him, this 23 meeting you-all had five hours after this occurred? 24 A. As I told you before, I don't remember this 25 meeting, so obviously I did not discuss it with him. 100 1 Q. Did you ever see the PR document? 2 A. No. I don't remember that. Remember, I left 3 several months after this and was involved in a number of 4 other projects. 5 Q. Yeah, but Doctor Beasley's still there, isn't 6 he? 7 A. I believe so. 8 Q. The next paragraph says, "Note: Systems will 9 query the database as to any deaths in ongoing blinded trials. 10 If there are deaths in one or any of these trials," then it's 11 cut off there, but it looks like it says, "then corporate 12 decision will have to be made as to whether to unblind the 13 particular trial to obtain an accurate denominator." Does 14 that look like what that says? 15 A. Yes. That looks like that. Uh-huh. Which 16 brings up actually a very interesting point which I hadn't 17 thought of, but perhaps you don't want to discuss that. 18 Q. I think the most interesting point here is that 19 you're having a meeting five hours after this occurred; you're 20 looking at your deaths that have occurred in connection with 21 Prozac and you're figuring out ways to look at those deaths, 22 and then you're going to turn it into a PR document. That's 23 what I find interesting. 24 A. Well, one could certainly read that into this, 25 but I think what one also can and should read is that there's 101 1 going to be a very thorough, honest systematic analysis of all 2 the available information. 3 Q. It makes me wonder whether if you're saying all 4 of a sudden there's going to be a thorough, honest systematic 5 evaluation, why you didn't have something that was thorough, 6 honest and systematic before this happened. 7 A. Because as I explained several times, this is an 8 ongoing process. And the last paragraph that's cut off here 9 talks about ongoing blinded trials. 10 Q. I understand that. I understand that. You're 11 not going to know exactly what's going on in unblinded ongoing 12 clinical trials, but this product has been on the market for 13 two years almost, hasn't it? 14 A. Yes. 15 Q. There have now been millions of people exposed 16 to the product, haven't there? 17 A. Yes. But not in controlled clinical trials as 18 what we're talking about here. 19 Q. I understand that. But this doesn't suggest 20 anything. This is talking about looking at your clinical 21 trial database; right, sir? 22 A. Yes, sir. 23 Q. Was there any suggestion made concerning -- in 24 addition to looking at people that may have died during the 25 clinical trials, let's look at how many people have died since 102 1 this drug has gone to market and this product has been used by 2 physicians who were not trained psychiatric investigators and 3 are not administering it according to our protocol. Did 4 anybody ever look at that? 5 A. That's not discussed in this memo. 6 Q. Well, do you have any independent recollection 7 that that was discussed as a possible source of information 8 that would be appropriate to look at under these 9 circumstances? 10 A. I know that was an ongoing evaluation as 11 reflected by the periodic reports to the FDA, those 1639s were 12 always reviewed. 13 Q. Were you involved in that as a clinical research 14 physician? 15 A. Earlier before approval. After that, I was not 16 involved on a day-to-day basis. 17 Q. Did you serve as a consultant or did Doctor 18 Beasley and Heiligenstein come to you and ask questions about 19 particular 1639s or reporting or things of that nature? 20 A. Not really about particular 1639s, no. 21 Q. Well, did they ask you about 1639s generally? 22 A. No. My role was more in how do we develop 23 fluoxetine and other areas, where should we go with that 24 struggle. It was really, as time went by, more and more on a 25 regular basis rather than particular day-to-day events. 103 1 Q. I thought you were just responsible for the 2 U. S. clinical trials. 3 A. When I was the research physician for 4 fluoxetine, but after that when Doctor Beasley and 5 Heiligenstein and Wheadon became much more involved I took on 6 more of a global advisory basis. 7 Q. But you were still classified as a clinical 8 research physician, weren't you, Doctor Wernicke? 9 A. Actually I believe that that also changed at one 10 time and that to me is somewhat irrelevant who has what 11 designation. 12 Q. Well, what designation did you have as a 13 clinical research physician? 14 A. I was promoted to senior research physician. 15 Q. Senior research physician? 16 A. Yes, sir. 17 Q. Is it your testimony you didn't have anything to 18 do with 1639s reviewing as a senior research physician what 19 was occurring in the postmarketing experience? 20 A. I'm not sure that I didn't review any of the 21 postmarketing 1639s, but certainly as time went by and other 22 people took over that day-to-day activity, I was not involved 23 in looking at individual 1639s, that is true. 24 Q. Did you ever look at any 1639 after Prozac was 25 approved? 104 1 A. I don't remember specific ones, but I'm sure I 2 did because I was still involved at that time. 3 Q. Did the issue -- were you still interested in 4 the issue as to whether or not Prozac is a safe and effective 5 drug? 6 A. Yes. 7 Q. And was part of your duties in connection with 8 that as a clinical research physician to look at 1639s? 9 A. There certainly was at some time, yes. 10 MR. SMITH: Could we approach, Your Honor? 11 (BENCH DISCUSSION) 12 MR. SMITH: This man is handling this witness, 13 isn't he? He put this witness on. He's got to make the 14 objections. This is -- 15 MR. McGOLDRICK: I didn't ask to come and pitch 16 here. 17 MR. SMITH: This is selected 1639s in connection 18 with adverse events. I intend to ask him if he reviewed them, 19 what information he did, what type of investigation was made. 20 MR. McGOLDRICK: Your Honor, please, two points. 21 One is my understanding and I have not been here and that's 22 why Mr. Myers is here and I believe Mr. Smith knows that, is 23 that individual 1639s have been ruled not to come into this 24 case. One, and so I would object to that. Two, respectfully, 25 with respect to certain matters that I, in fact, Mr. Myers 105 1 knows more because he's been living with this case all this 2 time, and I think it's helpful in fact to the Court if he's 3 able to speak. 4 JUDGE POTTER: You said there were two things. 5 MR. McGOLDRICK: The first one is the objection 6 that on the grounds to individual 1639s is not to be used and 7 I think Mr. Myers should be permitted to address that if 8 there's anything I'm not wear of. 9 JUDGE POTTER: Mr. Smith, didn't we go over 10 this? 11 MR. SMITH: We did specifically and you said 12 generally I'm not going to allow in 1639s on a global general 13 basis, however, that doesn't preclude you from asking in a 14 particular 1629 what they did to investigate a particular 15 adverse event. 16 JUDGE POTTER: What are you going to do? 17 MR. SMITH: I've got about -- these are all 18 pre-September 14th. There's one, two, three, four, five, six, 19 seven, eight, nine, ten, eleven, twelve. 20 JUDGE POTTER: All right. 20. 21 MR. MYERS: Judge -- 22 JUDGE POTTER: What do you propose to do? 23 MR. SMITH: Ask him if he was aware this was 24 reported. What he did to -- 25 JUDGE POTTER: Let me see one. I'm sorry. This 106 1 is wrong. It's particular sets. He can document. Are there 2 updates on these things? 3 MR. SMITH: Yes, sir. Most of them are on onset 4 dates. On the form it's going to be about right here. 5 JUDGE POTTER: Mr. Smith, thousands of these 6 things and just to go through and pick out one and argue with 7 him about what they did about it, I'm going to stick with my 8 ruling on that. And, first of all, he doesn't remember any 9 particular 1639. If you want to ask him generally what they 10 did, but I'm going to sustain the objection of taking him 11 through 1639 by 1639 and arguing with him about what he knows. 12 I'm going to sustain the objection. 13 MR. SMITH: Can I ask him about -- 14 JUDGE POTTER: You can follow up in general, if 15 he knows. 16 (BENCH DISCUSSION CONCLUDED) 17 Q. Doctor Wernicke, what was done to follow up by 18 Eli Lilly and Company as to -- let me back up. Were you aware 19 that there were reports of violent-aggressive behavior being 20 reported to Eli Lilly and Company in connection with use of 21 Prozac prior to September 14th, 1989? 22 A. I remember there were reports. I don't exactly 23 remember the dates, but since I remember them when I was there 24 and this was a few months before I left I would say yes, I 25 must have been aware of that. 107 1 Q. And do you remember, sir, that there were 2 reports made via 1639s of hostility, violent-aggressive 3 behavior, aggression and homicidal acts or homicidal ideation 4 in connection with Prozac via 1639s? 5 A. I remember all of those terms being in the 6 system, but I can't remember specific reports and that they 7 were linked, just that those kinds of things were handled in 8 the 1639 system. 9 Q. You say you do remember that you did have 10 reports of this? 11 A. I don't remember specific terms. I remember 12 that certainly when I was involved those were terms that were 13 in the system, but in terms of specific reports and what drug 14 patients were on, remember, we reported them even on 15 comparitors. I just don't have specific information on that. 16 Q. Well, you know, you had an event termed 17 hostility, did you not? 18 A. Yes. 19 Q. If it was reported that a patient became very 20 aggressive while taking Prozac after one week on the drug, had 21 an argument with another motorist and attempted to run over 22 that other motorist with a car, would that be a report of 23 hostility? 24 MR. McGOLDRICK: Judge, may I approach the 25 bench? 108 1 JUDGE POTTER: Objection is overruled. 2 A. I believe that would go in that term. I would 3 have to look at that dictionary, but that seems entirely 4 possible that that would go in under hostility or aggression. 5 I'm not just sure. 6 Q. If there was a report of hostility reporting 7 that a patient had become very aggressive after being on the 8 drug for one week -- 9 MR. McGOLDRICK: Judge? 10 JUDGE POTTER: Mr. Smith, where are we going? 11 Let me see you-all up here. 12 (BENCH DISCUSSION) 13 JUDGE POTTER: I don't think you can just read 14 it into the record. 15 MR. SMITH: I was just going to ask him if that 16 were reported what type of follow-up would be done. 17 MR. McGOLDRICK: Judge, it's more than that. 18 He's, with respect, standing there reading them. 19 JUDGE POTTER: He read the first one. What did 20 they do and what would they have done on something like that. 21 MR. SMITH: No. I'm still on the first one. 22 JUDGE POTTER: Ask him what would he do with 23 that one. 24 MR. SMITH: Okay. 25 (BENCH DISCUSSION CONCLUDED) 109 1 Q. Would there have been a follow-up by you or any 2 of the other clinical research physicians at Eli Lilly and 3 Company if it had been reported that a patient had become 4 hostile on Prozac, had an argument and attempted to run 5 somebody over with a car? 6 A. We followed up all reports on every event that 7 we felt there was any more information to be gleaned. If we 8 didn't feel that we had all of the available information, we 9 would follow it up. 10 Q. What would you do then, would you think this 11 would be information that would be sufficient: The patient 12 became very aggressive while taking Prozac after one week on 13 the drug, had an argument with another motorist and attempted 14 to run over the other motorist with his car? Would that have 15 been something that would have required further investigation? 16 A. If that was the only information I had, I would 17 certainly think that there would be other questions that I 18 would want an answer to. For instance, has he ever done this 19 before and what is his history, why is he taking the drug. 20 So, yes, there's a lot of information I would want to know. 21 Q. So there should be further follow-up? 22 A. I would certainly think that I would want more 23 information on that. 24 Q. If a patient became agitated and violent after a 25 third dose of Prozac and the patient was hospitalized and 110 1 Prozac was discontinued and the system -- 2 MR. McGOLDRICK: Judge, I hesitate to interrupt, 3 but... 4 JUDGE POTTER: Mr. Smith, I thought you were 5 taking it in one. No, just find out what they did. We're not 6 going to argue case by case on this. 7 MR. SMITH: I apologize. 8 You got information concerning what factors, 9 then, how long the patient had been on the drug? 10 A. Yes. That's what you told me. 11 Q. Would that be relevant, how long the patient had 12 been on the drug? 13 A. I certainly would want to know that. I don't 14 know if it's relevant, but I would want to know that. 15 Relevant implies cause and effect. It's relevant in the sense 16 that I think it's important information to have. 17 Q. But obviously the patient hadn't been on the 18 drug for two hours. That might be relevant in whether or not 19 the drug was causing the reaction, wouldn't it? 20 A. I'm sorry. You said if he had been on two 21 hours, it wouldn't be relevant. I think you need to know as 22 much about every case as you can and then you can come to some 23 sort of possible judgment. 24 Q. All right. Is it your testimony that Lilly did 25 that and that you did that? 111 1 A. I remember when I was doing -- working with the 2 1639s and the cases that I felt I needed more information, I 3 would try to get more information. 4 Q. If the patient's symptoms of violence and 5 aggression and hostility abated after Prozac was discontinued, 6 would that be something you would try to obtain? 7 A. I would try to obtain all information that I 8 could about this case, about the history, about the course of 9 events, what events occurred around it, what other medications 10 they were taking. There's a lot of information that one can 11 gather and one tries to get as much as possible. 12 Q. Did you see 1639s where there were doctors who 13 had reported that their patients had become violent, hostile 14 and aggressive on Prozac? 15 A. I don't remember specific 1639s in that -- with 16 those terms. 17 MR. SMITH: All right. Then, Your Honor, we 18 would move to refresh his recollection with the introduction. 19 JUDGE POTTER: You can let him look at a stack 20 of papers. 21 MR. McGOLDRICK: For purposes of refreshing on 22 that question? 23 JUDGE POTTER: Right. 24 I tell you what, ladies and gentlemen, why don't 25 we take the lunch recess. We're going to be quitting at 4:00 112 1 this afternoon so your afternoon won't be that long. And I 2 tell you what, why don't we do it this way. Why don't we go 3 till 1:30. All right? 4 As I've mentioned to you-all before, do not 5 permit anybody to speak to or communicate with you on any 6 topic connected with this trial, and any attempt to do so 7 should be reported to me. Do not discuss it among yourselves. 8 Do not form or express opinions about it. We'll stand in 9 recess till 1:30. 10 (LUNCH RECESS) 11 SHERIFF CECIL: The jury is now entering. All 12 jurors are present. Court is back in session. 13 JUDGE POTTER: Please be seated. 14 Doctor, I'll remind you you're still under oath. 15 Mr. Smith. 16 Q. Doctor Wernicke, during the lunch break, have 17 you had an opportunity to look at the set of 1639s that we 18 asked you to review? 19 A. Yes. 20 Q. And did you see any instances where it appeared 21 to you that there should be more investigation than was made 22 in connection with the reports reflected on the 1639s? 23 MR. McGOLDRICK: I thought that this was for the 24 limited purpose of refreshing recollection. 25 JUDGE POTTER: Well, he's refreshed his memory; 113 1 now he can ask him. 2 A. Well, I didn't look at them -- I understood the 3 question to be -- was did I remember any of these in specific. 4 In general, I would say there are many reports, many instances 5 where one would like to have more information but I didn't 6 look at these in particular with that question in mind, but I 7 would be glad to skim through them. 8 Q. Well, let me ask you this: You say just based 9 on your recollection you do have recollection of reports of 10 violent-aggressive behavior occurring in people who took 11 Prozac after the drug was approved; is that correct, sir? 12 A. No. My memory goes back really to when I was 13 very closely involved with the adverse-event monitoring before 14 approval, and I remember some aggression as a term but not 15 violent-aggressive behavior in that sense, just the term 16 aggression, but not after the marketing. 17 Q. All right. In connection with your noticing 18 reports of aggression in the clinical trials, did Lilly ever 19 run any clinical trials specifically designed to determine 20 whether or not it was the Prozac that caused the aggression 21 that was seen in patients during the clinical trials? 22 A. I'm not aware of any such trials. 23 Q. Did you ever recommend that such be done, Doctor 24 Wernicke? 25 A. No. 114 1 Q. Did you ever hear anybody at Eli Lilly recommend 2 that Lilly consider conducting a clinical trial on the issue 3 of whether or not Prozac caused aggression in individuals in 4 the clinical trial? 5 A. I don't remember any discussion exactly like 6 that, no. 7 Q. And you were the individual at Lilly that was 8 responsible for the United States clinical trials from, what, 9 1984 to 1987? 10 A. Roughly, yes, for depression and some other 11 indications. Other people became involved. 12 Q. Now, during the clinical trial phase did you 13 have reports of violence or homicide reporting? 14 A. I remember a case of a homicide specifically. 15 Q. What did you do -- did this occur during the 16 clinical trials? 17 A. I believe so, yes. 18 Q. What did you do to investigate that homicide? 19 A. I don't remember that specific instance and what 20 we did to investigate. In general, our policy was to try to 21 get as much information as we could. Often we would call the 22 physician or reporter if we could get hold of him. 23 Q. What did you learn about that instance of 24 homicide that was reported to you during the Prozac clinical 25 trial? 115 1 A. That the patient that was killed was actually 2 one of our patients and did not commit the murder, he was the 3 victim. 4 Q. All right. Were there any other reports of 5 homicide that occurred where patients were the perpetrators of 6 the homicide during the clinical trial? 7 A. Not that I can think of or remember. 8 Q. Was it ever reported to you reports of hostility 9 that occurred during the clinical trials? 10 A. I don't remember that term in particular. 11 Q. All right. Do you deny that there were 12 instances of any of the patients becoming hostile during the 13 Prozac clinical trials? 14 A. No, I don't deny that; I just can't think of a 15 particular instance right now like I did the homicide where I 16 remembered that being the term. That's all I can say. 17 Q. Do you remember generally that there was the 18 issue of hostility that was reported during the Prozac 19 clinical trial? 20 A. I remember aggression coming in as a term, and 21 whether that would have mapped to hostility or not I just 22 don't remember, but I remember that term was in the package 23 insert. What I'm basing my memory on is what went into the 24 package insert because that was the sum basis of our clinical 25 trial experience. 116 1 Q. Well, do you agree, sir, that aggression is part 2 of a continuum and that hostility could be on that continuum 3 of behavior? 4 A. That certainly is possible. 5 Q. All right. And then after hostility you could 6 get instances of intentional injury, could you not, on that 7 same continuum? 8 A. That would follow or run parallel with that. 9 Q. Would you agree that you could start with 10 anxiety and then move to agitation? 11 A. I think that's somewhat of a stretch, and I 12 would defer that to the psychopharmacologists and 13 psychiatrists for an opinion. 14 Q. So is it your opinion, sir, that when you see 15 anxiety in the Prozac package insert, that's not aggression? 16 A. I would not draw the conclusion that that is or 17 is not. I would look at those both independently and try to 18 establish if there was a link. I'm not sure that I have 19 enough information to really form a firm opinion about that. 20 Q. All right. Were there ever any clinical trials 21 to determine whether or not the aggression -- the aggression 22 that was reported could have been a result of the anxiety that 23 was reported during the clinical trials? 24 A. I'm not aware of any such trials and I'm not 25 sure how I would conduct that, but that would be something to 117 1 discuss, perhaps. 2 Q. Was that ever raised when you were supervising 3 the Prozac clinical trials? 4 A. Not at that time before approval that I was 5 involved, no, that I remember. 6 Q. But you do agree with me, sir, that you could go 7 from aggression to hostility to intentional injury? 8 A. I think that's reasonable. 9 Q. Was there ever any clinical trials to determine 10 whether or not Prozac was causing individuals to go from 11 aggression -- from aggression to hostility to intentional 12 injury? 13 A. Not that I'm aware of. 14 Q. Would you correlate agitation with aggression, 15 sir? 16 A. Not necessarily, because I know that it's such a 17 prominent feature of depression and I know that's a prominent 18 feature of many psychiatric illnesses. But from my 19 experience, limited as it may be, that was often usually not 20 associated with hostility or aggression toward other people. 21 Agitation is a restlessness and people walking, pacing back 22 and forth, but it's not directed harmful behavior, at least in 23 what I've seen. 24 Q. Would you agree that before one would become 25 aggressive it's likely that they would be agitated, sir? 118 1 A. Not necessarily. And, again, I'm not a forensic 2 psychiatrist but I've certainly read of cases where people 3 seemed to be as calm as everybody else and then commit mass 4 murder. So I would not make that correlation, but that's 5 basically not a nonpsychiatrist -- and certainly not a 6 forensic psychiatrist's level. 7 Q. In looking at these reports of aggression, 8 irritability, hostility and intentional injury, can you see 9 any instances where there was not enough investigation done to 10 determine all the facts necessary? 11 A. Well, if you look at -- certainly I would like 12 to know the past history and I don't see that in all the cases 13 -- the printing is rather poor -- and what other medications 14 might have been taken. Now, when you say investigation done, 15 what I can respond to is what's on these forms, and some of 16 these are initial reports. We understand of course that often 17 they are follow-up reports, and what these do not reflect is 18 the attempts made to get information. What's on here is 19 what's on here and that, yes, leaves some gaps that I would 20 like to know the answers to. 21 Q. Those that I have here leave some gaps as to 22 what you would need to know the answers to; is that right? 23 A. Some of them there is information that I would 24 certainly like to know. 25 Q. Can you see that? 119 1 A. Yes. 2 Q. It's my understanding that the German government 3 raised an issue of 13 suicide attempts at one time, and 4 you-all were of the opinion that in examining patient years 5 that there was no statistical significance of the 13 suicide 6 attempts on Prozac versus one on one comparitor drug; is that 7 correct? 8 A. That is correct. 9 Q. And your position is, is that patient years 10 would be the appropriate way to compute whether or not Prozac 11 was related to the suicide attempts? 12 A. That's important -- no. That's going one step 13 too far. What that's important in is to determine whether the 14 frequency was different. Even -- let me explain that. Even 15 if there were statistically significant difference, that does 16 not follow that Prozac caused those suicides. It may have 17 been that it's not as effective in that area and that allowed 18 those patients to commit suicide, but that does not establish 19 a causal relationship. That's a very important point. 20 Q. Well, but the point you were making I thought in 21 direct, that this number doesn't create any evidence that 22 Prozac was more likely to cause suicide than these comparitors 23 because the proper way to look at it is in patient years; is 24 that right, Doctor Wernicke? 25 A. What I said was is that those numbers in the 120 1 proper context do not support the conclusion that there is any 2 more -- frequently more rate -- higher rate of suicide and 3 fluoxetine. I did not talk about causal relationship and I 4 think that's a completely different question. 5 Q. All right. But what was key, as I understand 6 it, Doctor Wernicke, in your computation here, was the 7 patient-year computation; is that right? 8 A. That's correct. Yes. That's correct. 9 Q. When was the report of the 13 versus 0 versus 0 10 versus 1 versus 0? Was that in '85? 11 A. Yes. That -- well, in '84 that's what we sent 12 to the German affiliate and that was sent in '85, I believe, 13 to the FDA. 14 Q. You say this was raised in -- these numbers were 15 raised in '84? 16 A. They were in the NDA, which at least some of it 17 was submitted to the BGA. The BGA asked us to explain the 18 numbers, which we did in '84, and sent back to the German 19 affiliate, and that same submission, those two volumes were 20 sent to the FDA in '85. 21 Q. Were sent in '85? 22 A. I believe that's right with the IND annual 23 report, whatever that date is. 24 Q. Yeah. That's February 12th, '85. Okay? Well, 25 obviously, as you said, these things are continuing matters to 121 1 be analyzed, aren't they? 2 A. Certainly as events occur, yes. 3 Q. Look at Exhibit 227, Doctor Wernicke, and tell 4 me if you can identify that. 5 A. Yes. This looks familiar. It's a summation or 6 tabulation of suicide attempts and completed suicides. 7 Q. And this was done by Ms. Von Keitz and Doctor 8 Weber in Germany; correct? 9 A. Yes. 10 MR. SMITH: We'd offer Exhibit 227, Your Honor. 11 JUDGE POTTER: Be admitted. Ms. McBride. 12 COURT REPORTER: (Hands document to jurors). 13 Q. This document is dated October 3rd, 1986; 14 correct? 15 A. Yes. 16 Q. About nine months after the submission to the 17 BGA; correct? 18 A. Approximately. I don't know when it was exactly 19 submitted, but I would think that that would be right. 20 Q. And the suicide numbers have changed from these 21 numbers that were reflected and addressed in your original BGA 22 submission; correct, sir? 23 A. Yes. 24 Q. If we turn back to Page 2 of this document, on 25 Page 295 of this document, if you look at about the middle of 122 1 the page it's got some -- it reviews the various countries and 2 then it's got some totals, doesn't it? 3 A. I'm sorry. It has some what? 4 Q. Totals. 5 A. Oh, yes. Totals. Uh-huh. 6 Q. You see, it has suicide attempts. Now the 7 numbers have changed to 47 on Prozac, 2 on placebo, 2 on 8 amitriptyline and one on mianserin? 9 A. Mianserin. 10 Q. Mianserin; is that correct, sir? 11 A. Yes. 12 Q. And this was addressed to you; right? 13 A. Yes. 14 Q. These numbers were familiar to you? 15 A. Yes. 16 Q. We discussed these numbers in your deposition 17 several months ago in Houston, didn't we? 18 A. I believe that's correct. 19 Q. But you didn't mention these numbers in your 20 direct examination, did you? 21 A. These numbers? 22 Q. Yes. 23 A. No. I was using that example from the BGA 24 response. 25 Q. If you go down, Doctor -- well, Doctor Weber and 123 1 Ms. Von Keitz talk about total numbers of people on Prozac in 2 these comparitor drugs, does she not? 3 A. Yes. 4 Q. Then she starts talking about the last sentence 5 about patient years; correct? 6 A. Yes. 7 Q. Then if you turn to the first sentence of the 8 third page there, it says, "The relation is still not in favor 9 of fluoxetine even if patient years are considered," doesn't 10 it? 11 A. Yes. I see that. 12 Q. Did you advise the BGA of these figures, Doctor 13 Wernicke? 14 A. Remember, I do not and did not communicate 15 directly with the BGA, but I do know that part of this was 16 incorporated into the submission, this analysis of data that 17 ultimately led to the BGA approving the drug. 18 Q. But that data is not in this work, is it? 19 A. No. This is in 1986; that's in '84. 20 Q. And can you point to any specific document where 21 you forwarded these numbers on to the BGA? 22 A. I did not forward numbers to the BGA; I sent 23 them to the affiliates. We did this in preparation for 24 submission to the BGA. I participated in this exercise of 25 gathering this worldwide data, in fact, set up the analysis or 124 1 the data collection methodology so we could address this. 2 Q. But if you look at the figures expressed in 3 Exhibit 227, if you consider patient years it says it's not in 4 favor of fluoxetine, doesn't it? 5 A. That's what Ms. Von Keitz says. What I don't 6 see are the confidence intervals for the P values, and I'm not 7 quite sure what she means "in favor of," especially because 8 she says still not. So what I am thinking is what she's 9 referring to is what was in another document where some other 10 company had shown that the suicide rate was in fact less. And 11 I'm just not sure. 12 Q. She's probably talking about this, isn't she? 13 A. Well, I'm just not sure. 14 Q. Well, did you sit down and say -- when you saw 15 this difference, did you sit down -- when she said, "The 16 relation is still not in favor of fluoxetine even if patient 17 years are considered," did you sit down and put these P values 18 and these statistical analyses to these figures? 19 A. I did not do that personally, that was done by 20 statisticians, but I believe that that was done and all of 21 those calculations were made. 22 Q. Why not? You were able to do it here. Why 23 don't you do that? Can you do that for us, Doctor Wernicke, 24 with these figures? 25 A. As I explained here, that this was an example 125 1 and those were the numbers that were generated. And I did 2 explain that that's a very sophisticated methodology, and I 3 certainly can't do that without a computer because I don't 4 have the equations and I don't have the numbers that I need to 5 do that. 6 Q. You were able to give us these figures here. 7 A. Because I had them written down from what the 8 statisticians had done. 9 Q. Did you call the statisticians over the weekend 10 or something to get these figures? 11 A. We had done that before in the last couple of 12 weeks. I made sure that I had those numbers. 13 Q. Oh, you talked to the Lilly statisticians in 14 preparation to come down here and give these figures? 15 A. That's correct. 16 Q. Why didn't you ask the Lilly statisticians to 17 apply their analysis to these figures, Doctor Wernicke? 18 A. Because I remember a large part of the issues 19 seemed to revolve around these BGA questions and the 16 or 13 20 versus 1, and I thought that was a very clear example that I 21 could use to illustrate those points. 22 Q. Well, this is a document that was being raised 23 by the BGA, too, wasn't it? 24 A. This is not a document from the BGA; this is an 25 internal memo of us discussing the numbers and what we have 126 1 found so far. This is not in response to anything the BGA 2 raised. 3 Q. But didn't you say you were going to have to 4 give this to the BGA, these figures to the BGA? 5 A. Yeah. In some form I would think that they 6 would be given to the BGA with the analyses attached. 7 Q. But you don't remember whether this was given to 8 the BGA, or are you saying it probably wasn't given to the 9 BGA? 10 A. No. What I'm saying is these are the numbers 11 before the statistical analysis was done. There's no 12 reference to that. This is Doctor Von Keitz's compilation 13 of -- Ms. Von Keitz' compilation of the numbers. That whole 14 analyses, it was my understanding, was then transmitted to the 15 BGA with the proper statistical techniques applied. But 16 that's my understanding, remembering that I submitted 17 information to the German affiliate and then they compiled it 18 and submitted it. 19 Q. Well, did you ever have any discussions with Ms. 20 Von Keitz or Doctor Weber about these figures and about the 21 fact that even using the golden standard, you say, of patient 22 years it doesn't look good for fluoxetine? 23 A. When I saw that, my memory was that that -- 24 without a statistical comparison that's sort of a meaningless 25 statement. I don't react to that because, to me, it's in the 127 1 same order of saying that 13 looks bigger than 1. I want to 2 see the proper statistical comparison, and then I can render 3 some opinion. 4 Q. Well, but you rendered an opinion to this jury 5 that you've got to take that into account, patient years, 6 haven't you? 7 A. Absolutely. 8 Q. In here Ms. Von Keitz and Doctor Weber are 9 saying if you take in patient years, these figures aren't 10 favorable to fluoxetine; correct, sir? 11 A. That is correct to that point. And then I went 12 on to explain that one compares those by looking at the 13 confidence intervals, just as .027 doesn't look favorable 14 compared to 0. One could look at that and on that level one 15 would say, well, that doesn't look good. But one can't stop 16 there. That was the whole point of that example. One has to 17 do the formal unbiased analysis of all the data. 18 Q. Did you consider at this time during the 19 clinical trial to determine whether or not Prozac caused 20 suicidality in individuals? 21 A. We looked at that in every trial. I'm not sure 22 that I -- unless I sat down and planned it very carefully, 23 that I could figure out how one would do that trial. I think 24 it perhaps could be done. But the answer to your question is 25 no, we did not consider doing a specific clinical trial to 128 1 look at that issue. 2 Q. Did you consider employing some specific 3 questionnaires designed specifically to measure suicidality in 4 individuals in the clinical trials, Doctor Wernicke? 5 A. No. I was not involved in any such discussion. 6 Q. You were the clinical monitor responsible for 7 the trial from '84 to '89, weren't you? 8 A. Yes. 9 Q. While we have this out, these figures on use of 10 concomitant medications that we have been explaining here to 11 the jury; right? 12 A. Yes. 13 Q. That's just for one protocol, isn't it; that's 14 just for Protocol 27 data? 15 A. That's correct. 16 Q. That's not the entire U. S. clinical trial data, 17 is it? 18 A. No. 19 Q. That's not the entire worldwide clinical trial 20 data, either, is it? 21 A. Of course not. 22 Q. In fact, Doctor Wernicke, to jump back and forth 23 -- and I apologize for jumping back and forth with you -- Item 24 Three of the Hamilton Depression Scale that was used in the 25 Prozac clinical trials is not a good predictor of suicidality, 129 1 is it? 2 A. I don't believe it's meant to be a predictor. 3 It is never thought of as that. The whole Hamilton scale, 4 including that item, is a measure of current state. It's 5 never considered as a predictor, as far as I know. 6 Q. And it's not an adequate tool to use to 7 determine whether or not any drug is causing or not causing 8 suicidality, is it, that Item Three of the Hamilton Depression 9 Scale? 10 A. I am not aware of any study or consideration or 11 any method where that was looked at to see if the Hamilton 12 scale is a predictor. That has to be done in a separate 13 validation analysis. 14 Q. And I'm going to try not to cluster the record 15 with any more exhibits than I have to, but you have said, have 16 you not, Doctor Wernicke, that the suicide factor on a HAM-D 17 does not provide an accurate predictor, thus, we do not 18 advocate that it be used in the place of the investigator's 19 judgment, talking about suicidality? 20 A. Yes. That was in response to some inquiry we 21 had about whether that should -- the Hamilton Depression Scale 22 suicide factor should be used to exclude patients, and the 23 purpose of that is to say that the investigator's opinion is 24 what matters most, that this is not meant to be a predictor; 25 that's correct. 130 1 Q. HAM-D Item Three is not an adequate predictor of 2 suicidality, is it? 3 A. That was my opinion, yes. 4 Q. You wrote protocols for the Prozac clinical 5 trials? 6 A. Yes. 7 Q. You oversaw the Prozac clinical trials? 8 A. Many of them, not all. 9 Q. You've given us -- explained to us this time 10 line of what occurred during the Prozac clinical trials, have 11 you not? 12 A. Yes. 13 Q. In all honesty, the Prozac clinical trials, each 14 clinical trial themselves, really only averaged six to eight 15 weeks, didn't it? 16 A. The short-term controlled portions did; of 17 course, the extensions and the open label, much, much longer. 18 Q. Yes. But there wasn't that many extension and 19 open-label data that was used to support safety and efficacy 20 of this product, was there? 21 A. I would not agree with that, because the total 22 duration on extension and open label is quite extensive, and 23 most patients would go into an extension, certainly not all. 24 So the mass of data I think was substantial. 25 Q. Okay. But the blinded portion, the placebo 131 1 comparison portion, the comparitor comparison portion; right? 2 A. Yes. 3 Q. It's the guts, you say, of any scientific 4 analysis of a product. In the Prozac clinical trials the 5 average trials only lasted six to eight weeks, didn't they? 6 A. That's true. The comparitor portion, yes. 7 Q. Less time than we have spent together in this 8 courtroom, those of us who've been here throughout this trial; 9 correct? 10 A. As far as I know, yes. 11 Q. The analysis, the double blind, the placebo 12 control, the comparitor analysis where patients were given 13 this drug and compared with other patients who either got 14 placebos and/or comparitors, actually took less time than we 15 have been here in this trial; isn't that right, Doctor 16 Wernicke? 17 A. For any single trial, that is correct, as is 18 done with other drugs of this type, yes; that's correct. 19 Q. And the data where we see comparisons, Prozac 20 versus placebo, and Prozac versus placebo and comparitor, 21 every time we see that data, generally speaking we're talking 22 about an analysis of people who got Prozac for less time than 23 we've been here in this trial; right, sir? 24 A. Well, for six weeks is what the typical study 25 was. 132 1 Q. We've been here six weeks, sir. 2 A. All right. 3 Q. In your review of the clinical trial, did you 4 ever consult the guidelines for clinical trial evaluation of 5 antidepressant drugs published by the United States Department 6 of Health, Education and Welfare, Food and Drug 7 Administration, sir? 8 A. I don't remember specifically. 9 Q. Let me give you a copy. 10 A. This is a document that was published back in 11 1977 that's entitled Guidelines for the Clinical Evaluation of 12 Antidepressant Drugs; it's put out by the FDA. Did you get a 13 copy of that or did anybody provide you with this document 14 when you started with Lilly and started being the medical 15 monitor for the Prozac depression clinical trials? 16 A. I don't remember specifically this document and 17 certainly not in its entirety. 18 Q. It says it's put out in the abstract with the 19 Food and Drug Administration in conjunction with the 20 Pediatrics Committee on Drugs and in consultation with the 21 Pharmaceutical Manufacturers Association has put out this 22 guideline. It says the purpose is to present acceptable 23 approaches to the study of drugs. 24 A. Yes. 25 MR. McGOLDRICK: Your Honor, may I approach the 133 1 bench briefly? 2 (BENCH DISCUSSION) 3 MR. McGOLDRICK: If Your Honor please, I'm going 4 to object to the use of this document unless there's some 5 foundation laid that this was what was applicable at the time, 6 either when he was there or at some other point that somehow 7 he can establish as a foundation for having it in. This is 8 before the man was there, some seven years. 9 JUDGE POTTER: What is the purpose of this, 10 Mr. Smith? 11 MR. SMITH: There's a lot of rules in here about 12 the use of concomitant medication, the use of psychotropics 13 and things of that nature that I'm going to question him 14 about. 15 JUDGE POTTER: Where did this thing come from? 16 MR. SMITH: It comes from the FDA. It had not 17 been revised in September 1987, and this was the pamphlet that 18 was applicable during the Prozac clinical trials and we've 19 provided this to Counsel. 20 JUDGE POTTER: Is there anybody here that is 21 going to be able to identify this for you? 22 MR. SMITH: I don't have anybody here. 23 MR. McGOLDRICK: I don't know, Judge. This 24 Witness just said he had not been privy to a copy of this. 25 JUDGE POTTER: Is there any doubt that this is 134 1 what it's supposed to be? 2 MR. McGOLDRICK: Not in my mind, Judge. I'm not 3 here to assert that; what I'm here to assert is that it bears 4 the date 1977, which I fear is not, without more showing that 5 it's applicable to the time periods in question. It may be; I 6 don't know that. 7 JUDGE POTTER: The objection is that this thing 8 is dated in 1977? I mean, it's guidelines. Guidelines are 9 guidelines. If he wants to examine him about it, if the only 10 objection is that it's 1977 and he was doing this in the '80s, 11 I'm going to overrule the objection. 12 MR. SMITH: We would offer the exhibit, Your 13 Honor. 14 (BENCH DISCUSSION CONCLUDED) 15 MR. SMITH: We'd offer Exhibit 233, Your Honor. 16 JUDGE POTTER: Be admitted. 17 SHERIFF CECIL: (Hands document to jurors). 18 Q. Let me go over with you, Doctor Wernicke, I'll 19 say for the second time I'm not going to cover each section, 20 but if you look with me on Page 1, Section 1.0 is 21 introduction. In the second paragraph of Paragraph 1.1, the 22 second sentence says, "These guidelines, they are not intended 23 neither as minimum standards nor as unrealistic standards of 24 excellence, but are written with the hope of improving the 25 quality and meaningfulness of clinical studies that design to 135 1 evaluate new psychotropic drugs." Correct, sir? 2 A. Yes. 3 Q. Then he gives a lot of guidelines. Turn to 4 Page 4, under Section 2.0, Paragraph 2.2 in connection with 5 Phase 1 studies; do you see that, sir? 6 A. Yes. 7 Q. The last sentence of that Paragraph 2.2, the 8 first paragraph there, it says, "Generally should require no 9 concomitant medications." Right, sir? 10 A. Yes. In Phase 1, that's correct. 11 Q. Now, is it your understanding that it's okay to 12 have concomitant medication in Phase 2 and 3 trials? 13 A. Well, in Phase 2, I think that would be less 14 desirable. In Phase 3, certainly the less concomitant 15 medication of any type the better, but one has to recognize 16 that these people are quite ill and that they have symptoms 17 that sometimes need to be treated with concomitant medication. 18 Q. Well, these are guidelines for evaluation of 19 antidepressant drugs in people suffering from depression, 20 isn't it, Doctor Wernicke? 21 A. Yes. 22 Q. So we're not talking about two separate kinds of 23 trials, are we? We're talking about something directly 24 applicable to your Prozac trials, aren't we? 25 A. You were talking about Phase 1 trials so those 136 1 are somewhat different types of trials than Phase 3 trials 2 which are in the general population. 3 Q. I know that. What I'm talking about is this 4 pamphlet is applicable to Prozac trials because this is a 5 pamphlet on how to administer depression trials of 6 antidepressant medications; isn't it? 7 A. Yes. That's applicable. 8 Q. So it says you shouldn't have concomitant 9 medications in Phase 1, doesn't it? 10 A. Yes. 11 Q. All right. Let's turn to Page 6 and it will 12 talk about Phase 2. "The purpose and objectives of Phase 2 13 overall are to identify symptoms." Right? 14 A. Conditions or symptoms. 15 Q. "To estimate the appropriate clinical dosage." 16 Correct? 17 A. Yes. 18 Q. "And duration of effects." Right? 19 A. Yes. 20 Q. "And to identify adverse effects." Right? 21 A. Correct. 22 Q. Then look at Paragraph 3.2, the second full 23 paragraph under Paragraph 3.2: "As determined by 24 comprehensive clinical and laboratory evaluations, patients 25 evaluated early in this phase should require no concomitant 137 1 medications and have no organic diseases that may obscure 2 clinical observations, laboratory tests or interpretations; 3 correct, sir? 4 A. That's under 3.2? 5 Q. Yeah. 6 A. Yes. Go ahead. 7 Q. It's on Page 6. Do you see it now? 8 A. I was looking under 3.2.2. 9 Q. Do you see Sample Selection? Right here. 10 A. Oh, there you are. Right there. I'm sorry. 11 Q. I'll read it again. "As determined by 12 comprehensive clinical trial and laboratory evaluations, 13 patients evaluated early in this phase should require no 14 concomitant medication; right, sir? 15 A. Yes. 16 Q. Did you know that Doctor Fuller and the Prozac 17 fluoxetine team early in Phase 2 allowed for concomitant 18 medications, benzodiazepines and sleeping pills to control 19 agitation that was seen in the Prozac trials? 20 A. I had heard that and I saw that in some of the 21 early protocols. 22 Q. All right. Let's turn to Page 10. You see 23 where it talks about dosage? 24 A. Yes. 25 Q. Look at the paragraph directly above that. See 138 1 that? 2 A. Yes. 3 Q. It says, "Packaging and coding medications 4 should be performed on an individual basis rather than on a 5 treatment group basis. Other psychoactive drugs are to be 6 avoided. If other drugs are used, this should be carefully 7 documented." Correct, sir? 8 A. Yes. 9 Q. Now, you didn't avoid psychoactive medications, 10 benzodiazepines in the Prozac clinical trial; right? 11 A. They were allowed; they were not encouraged. 12 I'm not sure "avoided" is correct. Investigators were told 13 that if patients needed them and they were clinically 14 indicated that they were allowed to use a very limited number 15 of these drugs. 16 Q. But it didn't say limited, it said used in the 17 investigator's discretion to control agitation, didn't it? 18 A. Yes. But a very small number of drugs were 19 allowed. It's not that any drug could be given. Generally 20 two or three short-acting drugs were permitted. 21 Q. Did you disallow any particular psychoactive 22 medication when you were the medical monitor on these trials, 23 Doctor Wernicke, because some investigator was giving too much 24 concomitant medication or the wrong kind of psychoactive 25 medication? 139 1 A. We didn't disallow those in response to that. 2 We allowed a few medications to be given if the patients had 3 symptoms that warranted their use. 4 Q. Yeah. To control agitation; right, sir? 5 A. Or to treat the symptoms of their depression, of 6 which agitation and insomnia and anxiety are some. 7 Q. Patients were getting medication to control 8 their agitation in about 20 percent of the patients, weren't 9 they? 10 A. Twenty percent of the patients were given 11 concomitant medications because they reported some of those 12 adverse events. 13 Q. All right. It says, "If other drugs are used, 14 this should be carefully documented." Right, sir? 15 A. Yes. 16 Q. Was there any analysis made of the amount of 17 benzodiazepines, dosagewise, that were given to these 18 particular patients? 19 A. At the time of the NDA, that was not done that I 20 know of. 21 Q. Was there any analysis made of the time over 22 which particular patients were given particular 23 benzodiazepines? 24 A. Well, I did that afterwards recently, not -- 25 when you say ever done, it was done but very -- quite 140 1 recently. 2 Q. You did that quite recently, sir? 3 A. Yes. That's what I mean, yes. 4 Q. In response to questions that were directed to 5 you by Counsel? 6 A. Yes. 7 Q. Do you know why it is that since you've been 8 gone from Eli Lilly and Company since December of 1989, that 9 you've been asked to come up here from Houston to give your 10 testimony? 11 A. Well, I was very much involved in the whole 12 regulatory and approval process, so I didn't think to question 13 it any further than that. I was there when a lot of these 14 things went on. 15 Q. Well, so was Doctor Beasley, wasn't he? 16 A. He wasn't really there at the time of the safety 17 update, and all of that I did. That was before his time. 18 Q. Is it your understanding that Doctor Beasley is 19 not going to appear here? 20 A. I have no information on that. 21 MR. McGOLDRICK: If Your Honor please, I'm not 22 sure that's up to this Witness. 23 JUDGE POTTER: Yeah. I don't know that he's 24 qualified to answer, Mr. Smith. 25 Q. Okay. Let's go to Phase 3 that begins on 141 1 Page 12. It says, "By the middle or end of Phase 3, 2 sufficient information should be available to formulate 3 hypotheses as to the types of patients and their clinical 4 conditions which may respond to the investigational drug. For 5 testing these hypotheses, control trials are necessary. This 6 is the major purpose of Phase 2 studies -- 3 studies." 7 Correct, sir? 8 A. Except in the beginning I think you read it by 9 the middle or end of Phase 3; it says Phase 2. That's that in 10 the evolution and then you do Phase 3, yes. 11 Q. "But by the middle or end of Phase 2, sufficient 12 information should be available to formulate hypotheses as to 13 types of patients and their clinical conditions which may 14 respond to the investigational drug. For testing these 15 hypotheses, control trials are necessary. This is the major 16 purpose of Phase 3 studies." Right? 17 A. Yes. 18 Q. There were no Phase 3 studies done specifically 19 to examine whether or not Prozac causes agitation in 20 particular individuals, were there? 21 A. No, because agitation is not a disease. 22 MR. SMITH: Object to that as being 23 nonresponsive, Your Honor. That's capable of being answered 24 yes or no. 25 JUDGE POTTER: Let him answer his question and 142 1 then if you need to explain it, he can. 2 A. Well, the way studies are developed is for an 3 indication for a disease in that their purpose of Phase 2, as 4 I explained earlier, are pilot experiments, pilot studies, to 5 see if there's a potential utility for treatment of a disease, 6 be it depression, cancer, anything else. And then the Phase 3 7 studies are launched to test that hypothesis, not to 8 specifically look at elements of that. It always has to be 9 related to what we call a nosological entity, or a disease. 10 Q. Doctor Wernicke, were any Phase 3 trials done 11 specifically to examine the issue of whether or not Prozac 12 caused agitation in individuals? 13 A. Not to my knowledge. 14 Q. Were there any Phase 3 clinical trial studies 15 done specifically designed to determine whether or not Prozac 16 caused violent-aggressive behavior or hostility in 17 individuals? 18 A. Not specifically designed. 19 Q. And there were none on suicidality, either, were 20 there? 21 A. As far as I know; that's correct. 22 Q. And in 1984 and 1985, when this issue was raised 23 by the German government, you were into Phase 3 trials, were 24 you not, sir? 25 A. Yes. 143 1 Q. Go with me to Section 4.2, Patient Selection. 2 Do you see that? 3 A. Yes. 4 Q. In that first paragraph there, the second 5 sentence says patients -- it says, "Populations with other 6 than primary depressive disorder, such as depression with 7 schizophrenia or in association with anxiety or with medical 8 conditions, may be studied in separate trials." Right, sir? 9 A. Yes. 10 Q. There were no Prozac studies on individuals with 11 schizophrenia, were there? 12 A. That's correct, to my knowledge. 13 Q. There were no Prozac studies with patients with 14 depressive paranoid depression, psychotic depression, were 15 there? 16 A. Not specifically as an inclusion criterion; 17 that's right. 18 Q. There were no Prozac clinical trials to examine 19 the effect of Prozac on individuals with schizoaffective 20 disorder, were there, sir? 21 A. To my knowledge, that's correct. 22 Q. Schizoaffective disorder is a disorder that can 23 be seen in individuals who are suffering from depression? 24 A. I'm not sure I'm the best qualified to answer 25 that, but it's always been my understanding that that is not 144 1 truly within the scope of major depressive disorder. It was 2 always my understanding that that is not correct, that that's 3 something you see -- that's really a separate diagnosis. 4 Q. Schizoaffective disorder is a milder form of 5 psychotic depression, isn't it? 6 A. Again, I don't feel that I'm really best 7 qualified to answer that. I'm not a psychiatrist and I'm not 8 sure of the current way that they're thinking about these 9 diagnoses since I've been out of this area now for about five 10 years. 11 Q. Let me ask you this, Doctor Wernicke: Were any 12 Prozac clinical trials done on individuals suffering from 13 psychotic depression? 14 A. Not to my knowledge. 15 Q. Were there any Prozac clinical trials done on 16 individuals suffering from schizoaffective disorder? 17 A. Not that I'm aware of, no. 18 Q. Is Prozac contraindicated in the package insert 19 for individuals suffering from psychotic depression? 20 A. Not that I know of. 21 Q. Is Prozac contraindicated in the packaging 22 information in individuals suffering from schizoaffective 23 disorder? 24 A. No. 25 Q. It is not, is it? 145 1 A. No. 2 Q. There is some discussion of that, though, isn't 3 there, on Page 9 of this pamphlet? 4 A. I'm sorry, what page? 5 Q. Page 9. Look at Point 6 on the top of the page. 6 A. Yes. 7 Q. It says, "It is desirable that a variety of 8 sociodemographic and clinical characteristics of the patient 9 be reported. These characteristics include age, sex, racial 10 or ethnic background, social class, previous hospitalizations, 11 previous diagnoses of mania or schizophrenia and previous 12 major therapies; i.e., ECT, phenothiazines, et cetera." 13 A. Yes. That's correct. 14 Q. It says in Seven, "It is recommended that the 15 criteria for exclusion be identified particularly for patients 16 in the borderline between schizophrenia and the affectiveness 17 diseases." Correct, sir? 18 A. Yes. 19 Q. And that's smack-dab where schizoaffective 20 disorder falls, isn't it, sir? 21 A. My understanding of it is somewhere in between 22 those two. 23 Q. Turn with me to Page 7, Item 3, right at the 24 middle of the page. Do you see that, sir? 25 A. Yes. 146 1 Q. It says, "Where antidepressant drugs are being 2 used for depressive symptoms accompanying other psychiatric 3 conditions, this indication should be specified in the 4 protocol and the diagnosis criteria identified. In practice, 5 three such populations have been involved in antidepressant 6 drug trials. These are, A, alcoholics; B, schizophrenic or 7 schizoaffective states. The criteria for diagnosis should be 8 specified." Correct, sir? 9 A. Yes. 10 Q. And, C, aged patients. Right? 11 A. Yes. 12 Q. As I understand it, though, Doctor Wernicke, you 13 had never seen Exhibit 233 before? 14 A. Not in its entirety. I remember some of these 15 elements having seen them, but all of these pages stapled 16 together like this I just do not remember, but I do remember 17 some of these issues. 18 Q. Well, look with me at Page iii, under the 19 Forward section there in the front. Do you see it? 20 A. Yes. 21 Q. It would be third-from-the-bottom paragraph. It 22 says, "Many of the clinical guidelines have been developed 23 largely or entirely by FDA's advisory committee and 24 consultants. Others were originally developed by intramural 25 committees and consultants of the FDA and of the 147 1 Pharmaceutical Manufacturers Association. In these cases the 2 guidelines were reviewed and revised as appropriate by FDA's 3 advisory committee." Correct, sir? 4 A. Yes, sir. 5 Q. While I'm looking for this, let me ask you a 6 couple of questions about this 1985 advisory committee 7 meeting. You were there, weren't you, Doctor Wernicke? 8 A. Yes, I was. 9 Q. You didn't advise the German government -- I 10 mean, you didn't advise the United States Food and Drug 11 Administration anything at all about the fact that the BGA had 12 raised these questions on whether or not Prozac was an 13 activating antidepressant, did you? 14 A. We submitted all of that material, I believe, 15 before then. 16 Q. No. I'm talking about what you told them there, 17 sir. Did you say anything to them about the fact that the 18 German government had raised this issue? 19 A. I don't remember any conversations about any 20 specific government's questions or any specific questions. We 21 reviewed our database and our findings. 22 Q. The issue of the foreign government question 23 wasn't even raised in 1985, was it? 24 A. Not at the advisory committee, as I remember. I 25 can't be absolutely certain. 148 1 Q. The issue of concomitant medications as far as 2 reducing dosages in addition to using concomitant medications 3 was not raised, was it? 4 A. I vaguely remember a discussion of dosage but 5 not any more in specific about concomitant medication. I just 6 don't remember that. 7 Q. You didn't tell the FDA advisory committee that 8 you were reducing the dosages as well as using concomitant 9 medications to control this agitation, did you? 10 A. I'm not sure we reduced dosage to control 11 agitation. I think that's one of those presumptions from 12 which follows a question. 13 Q. We have documents that say you did and Fuller 14 said you did. 15 A. As I remember, that was our model, and dosages 16 were reduced in some cases. That may well be. All of that 17 information was reported to the FDA in the study reports. 18 Q. Doctor Wernicke, again, I'm talking about what 19 you told this advisory committee meeting that you said 20 unanimously approved in 1985 the product. 21 A. I don't remember discussing dosage and changes 22 in dosage in particular. 23 Q. The fact is you didn't, did you? 24 A. Well, as I just said, I don't remember that. If 25 I read the whole transcript then I could say whether I did or 149 1 did not. 2 Q. Okay. You certainly didn't tell the FDA 3 advisory committee in 1985 that on September 11th, 1984, 4 Doctor Schenk had recommended that Prozac be used only with 5 concomitant medications in agitated and suicidal patients, did 6 you? 7 A. I don't believe that that was discussed, 8 certainly not by me. 9 Q. I want to switch gears with you a little bit, 10 Doctor Wernicke. Look at Exhibit 79. Have you got it? 11 A. Yes. 12 Q. It's kind of hard to read. It says, "Charlie, 13 let me ask for your help in putting together two slides for 14 the board." And this is Doctor Leigh Thompson; right? 15 A. Yes. 16 Q. It says, "I've got to say something about 10 17 milligram, both in regard to attributes and to the logistics 18 of when we will file in the U. S. international filing is a 19 big, big problem." Correct, sir? 20 A. Yes. 21 Q. He says, "I don't think we have any 10-milligram 22 efficacy data. We do have the Wernicke study of 5 milligram 23 versus 20 and 40." Right, sir? 24 A. Yes. Yes. 25 Q. And that's this study that you were talking 150 1 about Friday; correct, sir? 2 A. Yes. 3 Q. It says, "Some people have massaged those data 4 to make 5 milligrams look not quite as good as 20 milligrams." 5 Right, sir? 6 A. That's what he says, yes. 7 Q. Now, when you gave your deposition in this case, 8 you told me that you were not aware that anybody had massaged 9 the data in your trial to make 5 milligrams look not quite as 10 good as 20 milligrams; correct, sir? 11 A. That's correct. 12 Q. Have you ever massaged data, Doctor Wernicke? 13 A. I don't know what that means. You have to put 14 that in a context of -- 15 Q. You told me in your deposition that you massaged 16 people, didn't you? 17 A. That's what one does, not that that's what I do. 18 But that's the correct use of that term. 19 Q. Well, you hadn't ordinarily seen the term 20 "massage" used in connection with a statistical analysis, had 21 you? 22 A. Well, except by Doctor Thompson. He uses words 23 like that; he has a very flowery language, and I might have 24 heard it. 25 Q. Well, you told me in your deposition in Houston 151 1 that you had never heard Doctor Thompson use such a word in 2 connection with statistics, didn't you? 3 A. I didn't remember at that time. I've heard it 4 so often since that I don't remember now. At that time I 5 certainly didn't remember it. 6 Q. Tell me honestly, Doctor Wernicke, have you gone 7 over this document a little bit with your attorneys -- or, 8 with the Lilly attorneys since I questioned you about this 9 document in Houston a couple months ago? 10 A. Well, I have looked at it, yes. 11 Q. And talked to them about it? 12 A. Yes. 13 Q. Now you remember maybe Doctor Thompson does 14 use -- did you say flowery words? 15 A. Well, this and others. I don't remember him 16 using that before, but I'm not surprised. 17 Q. But when I took your deposition, you told me 18 massage has a bad connotation in connection with statistics, 19 didn't you? 20 A. To some people. Depends on -- what I said, as I 21 remember, and this was also a few months ago now, that 22 depending on who used it, one would have to know that person 23 to know what their intent was. 24 Q. Were you aware of any massaging of this data 25 that you collected to make 5 milligrams look not as good as 152 1 20 milligrams, Doctor Wernicke? 2 A. No. I'm not aware of any such manipulation. 3 Q. Manipulation. You use the term manipulation. 4 Isn't that really what you're talking about when you say 5 massage? You're talking about manipulating data to make the 6 5 milligram look not quite as good as the 20? 7 A. If it were done with the intent of showing some 8 outcome and, in this case, making one dose look worse than 9 another, I would call that manipulating. 10 Q. And that's what was done, according to Doctor 11 Thompson, in this memo; correct? 12 A. According to Doctor Thompson he seemed to imply 13 that that may have been done. 14 Q. Are you aware of any other instances of 15 manipulation of this data concerning this important question 16 of dosage in Prozac? 17 A. I'm not aware of any circumstance of 18 manipulation of the data. 19 Q. Well, he says it occurred, doesn't he? 20 A. Well, he says that, but I would like to see the 21 evidence. 22 Q. Look with me at Exhibit 78 in that same 23 connection, Doctor Wernicke. 24 A. Yes. I have seen this. 25 Q. It says, "A decision has been made by Mr. Wood 153 1 to amend the fluoxetine fixed low-dose protocol. Upon his 2 recommendation, we will exclude the 10-milligram fluoxetine 3 dosage regimen." Correct, sir? 4 A. Yes. 5 Q. And this is in June of 1985? 6 A. Yes. 7 Q. And you were copied on that document, were you 8 not? 9 A. Yes. 10 Q. And the Mr. Wood that's referred to here is Mr. 11 Richard Wood, chairman of the board of Eli Lilly and Company; 12 correct, sir? 13 A. Correct. 14 Q. Master of Business Administration, not medical 15 doctor; correct, sir? 16 A. Yes. 17 Q. Of course, Eli Lilly in February of 1994, did 18 start manufacturing Prozac in 10-milligram pulvule form, did 19 they not, sir? 20 A. So I have heard, yes. 21 Q. And there had been recommendations for years 22 that Prozac be marketed in a lower pulvule dosage than 23 20 milligrams, hadn't there? 24 A. I don't have personal experience with that. I 25 have heard that there had been some requests, but I just don't 154 1 know the extent or the nature. 2 Q. But you're aware that it had been requested by 3 numerous psychiatrists on numerous different occasions; right, 4 sir? 5 A. On some occasions I remember discussions about 6 that and some inquiries coming in about that, but I really 7 don't have a good feel for how many instances that was. 8 Q. But it was done in February 1994, wasn't it? 9 A. That's what I have heard, and I believe that as 10 true, yes. 11 Q. In connection with schizoaffective disorder, my 12 recollection is you told me when you gave your deposition in 13 Houston -- 14 MR. McGOLDRICK: Judge, I'm sorry to interrupt, 15 but could I this one time? 16 (BENCH DISCUSSION) 17 MR. McGOLDRICK: Judge, I object to the form of 18 the question. I think if I understand things right, that 19 Mr. Smith is permitted to ask a question of the Witness and if 20 the Witness says differently something than he said in his 21 deposition, he can impeach the Witness with that. But I'm not 22 sure it's proper, and I don't think it is, for him to start up 23 by saying you said in your deposition X. 24 MR. SMITH: Okay. I won't say it. 25 JUDGE POTTER: Okay. 155 1 (BENCH DISCUSSION CONCLUDED) 2 Q. Is it correct, Doctor Wernicke, based on your 3 belief as the clinical monitor for Prozac, that 4 schizoaffective disorder presents a treatment challenge? 5 A. Well, all of these disorders represent a 6 treatment challenge. They're all serious disorders. I would 7 say yes, but not limited to that. 8 Q. And to treat Prozac with -- to treat 9 schizoaffective disorder along with major depressive disorder 10 would be a treatment challenge? 11 A. I think I would agree with that more first a 12 diagnostic challenge and then perhaps also a treatment 13 challenge. 14 Q. Explain to the jury why that is, Doctor 15 Wernicke, in your opinion, sir. 16 A. Well, again, I'm not a psychiatrist, but it's 17 always been my understanding that schizoaffective disorder 18 isn't in the same category of major depressive disorder, that 19 this is somewhat different. My understanding -- and this is 20 probably fairly simplistic -- is that there's schizophrenia 21 and there's affective disorder and these group of patients are 22 somewhere in between. And it's not, as far as I know, not 23 really clear whether they're a type of one or type of the 24 other or something really in and of themselves. But that is a 25 fairly basic understanding of what that is. 156 1 Q. But you do know that schizoaffective disorder 2 can and does exist in many people who are recognized as 3 depressed individuals? 4 A. They may carry that diagnosis. But what my 5 understanding is that they could have both or they may just 6 have more depressive features. It's not clear to me whether 7 these people have two disorders or whether they have one and 8 they're just showing more of one feature. 9 Q. Okay. But I think you said it's difficult to 10 diagnose whether or not an individual suffering from major 11 depression might have schizoaffective components to that major 12 depressive disorder. 13 A. It certainly would be difficult for me. I'm not 14 a trained psychiatrist. I can't speak for the others. 15 Q. But in this case Doctor Lee Coleman diagnosed 16 that Mr. Wesbecker was suffering from major depressive 17 disorder with schizoaffective components. Do you understand 18 that, sir? 19 A. I have heard that. I have not seen any records 20 actually in regard to that. 21 Q. And I believe that you have expressed the 22 opinion that treatment of schizoaffective disorder in that 23 situation presents a treatment challenge; right, sir? 24 A. It certainly would to me in my level of 25 understanding. 157 1 Q. Your impression was that schizoaffective 2 disorder by virtue of its schizo component should have an 3 antipsychotic administered? 4 A. I didn't say that. And although I would 5 certainly think that that would be rational, that really goes 6 beyond my knowledge of the current state of psychiatry. 7 Q. But you can say that it was well known at Lilly, 8 when you were the Prozac clinical monitor, that you could see 9 individuals with schizoaffective disorder who were also 10 suffering from major depressive disorder; right, sir? 11 A. Again, let me -- I'm not sure I can really say 12 that. What I do know is -- let me give another example and I 13 think it will clarify the way I think about it, is that if a 14 patient comes in with depressive features, that patient may 15 well have bipolar disorder, bipolar depression, but at that 16 moment all one sees is depressive features. And I think the 17 same could be applied to schizoaffective. As I understand it, 18 they may have psychotic features, but if they don't present 19 with those, if those don't show up at that time, one may not 20 know that. That's the best way I think I can explain how that 21 fits together. 22 Q. And Prozac is not contraindicated in people with 23 psychotic depression, is it? 24 A. That's correct. 25 Q. And it's not contraindicated suffering from 158 1 schizoaffective disorder, is it? 2 A. That's correct. 3 Q. And an individual can be experiencing depression 4 and schizoaffective disorder at the same time? 5 A. That's my understanding that that is so. 6 Q. Did you say Friday that animal models are a 7 predictor of the effects of drugs? 8 A. Well, in general for many drugs, many disease 9 states, there are animal models; for some there are none; for 10 some there are some that are thought to perhaps be related. 11 So there's a whole spectrum, but there is certainly not a 12 clear, totally predictive animal model for every disease 13 state. 14 Q. I understand that, but one of the reasons that 15 you do animal studies in Phase 1 is it can sometimes be a 16 predictor of the effect of the drug; correct, sir? 17 A. Before Phase 1. You usually do that actually 18 before Phase 1 and perhaps continue into Phase 1 and 2. 19 Q. Did you indicate on Friday that the 20 investigators, once they were hired, were brought to 21 Indianapolis and given courses on how to conduct the clinical 22 trial? 23 A. Those start-up meetings were usually not in 24 Indianapolis; sometimes they were. They were regional 25 meetings, depending on whatever city was easy for people to 159 1 come into, not necessarily in Indianapolis. 2 Q. I thought that you called the investigators into 3 Indianapolis from time to time where you sat them all down 4 together and you had somebody administering the Hamilton 5 Depression Scale on videotape and the investigator would rate 6 that individual and then you-all would compare ratings; is 7 that right? 8 A. That was part of the start-up meeting, not from 9 time to time, at the beginning of every study. And that might 10 have been in San Diego and Chicago, and those were held in 11 other cities, also. But that was a specific meeting called 12 the start-up meeting before the study actually started. 13 Q. And that was to get inter-rater reliability; is 14 that what you said? 15 A. Yes. That's correct. 16 Q. You don't mean intra-rater reliability? 17 A. It was called inter-rater reliability for right 18 or wrong, but that's the term I remember. 19 Q. Okay. So before these investigators ever began 20 a study, they would see videotapes made by Lilly and given 21 instructions by Lilly on how to administer the test? 22 A. I'm not sure we made all those tapes. I believe 23 some of them were bought from outside vendors that specialized 24 in these kind of instructional materials. I'm not absolutely 25 certain but, as I remember, that especially was done later on. 160 1 Q. I think that's all I have, Doctor Wernicke. 2 Thank you, sir. 3 JUDGE POTTER: Okay. Ladies and gentlemen, 4 we're going to take a brief recess. Since we're going to quit 5 at four, we'll just take a real brief recess. I'll mention to 6 you, don't talk about this with anybody; don't discuss it with 7 each other. We'll take a ten-minute recess. 8 (RECESS) 9 SHERIFF CECIL: The jury is now entering. All 10 jurors are present. Court is back in session. 11 JUDGE POTTER: Please be seated. 12 Doctor, I'll remind you you're still under oath. 13 Mr. McGoldrick. 14 MR. McGOLDRICK: Thank you, Your Honor. 15 16 FURTHER EXAMINATION 17 18 BY MR. McGOLDRICK: 19 Q. Doctor Wernicke, there was some questioning 20 earlier about mortality on medicines, and I have a few 21 questions about that. First of all, does Lilly keep data on 22 persons who die during the period of time when they are taking 23 the medicine? 24 A. Yes. 25 Q. And does that information relate to the cause of 161 1 death or is it just when there is a death? 2 A. All information is collected, cause of death 3 included. 4 Q. So that if I had a heart attack or the roof fell 5 on my head and I was taking the medicine, that would be 6 recorded? 7 A. Yes. 8 Q. In the clinical-study phase, is any death that 9 occurs, whatever the reason, whether it's on Prozac or the 10 comparitor medicine or the placebo, reported to the FDA? 11 A. Yes. 12 Q. After the clinical studies in the marketing 13 phase, the spontaneous reporting phase, are deaths that occur 14 on the medicine reported to the FDA? 15 A. Yes. 16 Q. Approximately during what period of time are 17 they reported? 18 A. Typically -- well, certainly at least quarterly, 19 and deaths typically after marketing are reported within 15 20 days. 21 Q. All right. By the way, is this reporting of 22 deaths unique to Prozac or is it true of any medicine that's 23 under clinical study? 24 A. It's true of all medicines. 25 Q. Whatever company makes it, they report it to the 162 1 FDA? 2 A. Yes. 3 Q. All right. Now, let me call your attention to 4 the date of September 14, 1989, the date of these terrible 5 events in Louisville that Mr. Smith was alluding to. Did the 6 German approval of the medicine come after September 14, 1989? 7 A. Yes. 8 Q. Let's turn again to the advisory committee, the 9 second advisory committee with respect to fluoxetine. Do you 10 recall when that was? 11 A. I believe, in '91. 12 Q. All right. Maybe I could quickly get that chart 13 up. Will this refresh your recollection as to when the 14 advisory committee that looked into suicidality and violence 15 occurred? 16 A. 9-20-91, in September. 17 Q. Where is that on the chart? 18 A. September 20th, 1991. 19 Q. Right here. Okay. Is September 20, 1991, well 20 after September 14, 1989, -- 21 A. Yes. 22 Q. -- when these terrible events occurred? 23 A. About two years later. 24 Q. And the FDA advisory committee at that time 25 concluded what about the medicine? 163 1 A. That there was no causal relationship between 2 suicidality or to the suicide events and the use of the 3 medication, to my understanding. 4 Q. All right. I'm going to refer to Exhibit 173, 5 which is in evidence, the talk paper of the FDA of that 6 advisory committee, again in October of 1991. And let me ask 7 you if showing you that third page and the middle paragraph 8 there refreshes your recollection as to what the FDA talk 9 paper said. 10 A. Yes. It says, "The committee unanimously agreed 11 there was no credible evidence of a causal link between the 12 use of antidepressant drugs, including Prozac, in suicidality 13 or violent behavior." And then it goes on to give some 14 quotes, and that's essentially what I remembered. 15 A. Okay. Thank you. 16 Q. And that's two years after the Wesbecker 17 shootings? 18 A. Yes. 19 Q. Doctor, you ran the 5-milligram, 20-milligram, I 20 guess 40-milligram fixed-dose study, did you? 21 A. Yes. 22 Q. And, very briefly, why did you run that? 23 A. To confirm the 20-milligram dose as being 24 effective, if that was the case, and to perhaps establish a 25 no-effect dose. 164 1 Q. And, again, very briefly, what did that study 2 show? 3 A. That 20 milligrams was effective, and somewhat 4 to our surprise 5 milligrams worked in a lot of patients, but 5 overall it was not as effective as the 20. 6 Q. Doctor, was there any manipulation of those data 7 or is that what they showed? 8 A. That is what they showed. 9 Q. Doctor, there was some interrogation about FDA 10 guidelines. Before any protocol for a clinical study is run, 11 does Lilly have to submit that protocol to the FDA? 12 A. Yes. 13 Q. Does Lilly do that? Does Lilly submit those 14 protocols to the FDA? 15 A. Yes. 16 Q. And does Lilly -- strike that. 17 If the FDA has any objections, they let you 18 know? 19 A. Yes. 20 MR. SMITH: Your Honor, we're going to have to 21 continue to object to the leading. 22 JUDGE POTTER: Sustained. 23 Q. Doctor Wernicke, when the protocols are 24 submitted, does the FDA do anything? 25 A. Yes. If they have a question or don't want the 165 1 protocol to be done, they can let us know within 30 days. If 2 we don't hear anything, then we may proceed at that time; 3 however, they may still raise questions later on. 4 Q. Thank you, Doctor, very much. Appreciate your 5 coming. 6 JUDGE POTTER: Thank you very much. Mr. Smith? 7 MR. SMITH: May we approach, Your Honor? 8 JUDGE POTTER: Yes. 9 (BENCH DISCUSSION) 10 MR. SMITH: Doctor Wernicke has just testified 11 that Lilly reports all deaths that occur in the clinical 12 trials in every clinical trial with respect to every drug. We 13 have evidence that Lilly did not report all deaths; that they 14 were sanctioned by the United States House of Representatives; 15 that the reporting requirements have been changed to add that. 16 They have opened the door to cross-examine Doctor Wernicke on 17 whether or not they did in fact report all deaths. 18 MR. McGOLDRICK: Judge, I think my questions 19 were clear in asking whether the deaths we were talking about 20 were in the clinical trials that Doctor Wernicke is dealing 21 with. I did not get into any other products. He didn't 22 understand me to get into any other products. Any other 23 products are entirely irrelevant to this case and highly 24 inflammatory. I don't think I opened any door and I would 25 object to any questioning of that sort in a most vigorous way. 166 1 MR. SMITH: I think if we look at the transcript 2 he said they reported all deaths on all trials. 3 JUDGE POTTER: You did ask -- you did ask, you 4 know, this is not just Prozac, this is every drug and all 5 that. 6 MR. McGOLDRICK: I did ask about other 7 companies, Judge. I said with respect -- and other companies 8 do this, to show it as a general rule. I did not on this 9 point -- 10 JUDGE POTTER: Well, okay. As I understand it, 11 Mr. Smith has got a document about another drug in another 12 case and you-all didn't report something for it; is that 13 right? 14 MR. SMITH: Yes. 15 MR. McGOLDRICK: That's what he alleges. 16 JUDGE POTTER: I mean, it's correct; right? 17 MR. McGOLDRICK: I believe so, Judge. 18 JUDGE POTTER: Mr. Smith, that is just very 19 highly inflammatory. I don't think it has very much probative 20 value here, if any, that they -- you know, they did what they 21 did here. But, you know, I'm going to sustain the objection 22 to adding in the House report on death in Ireland, was it, or 23 someplace that it reported. 24 MR. SMITH: In connection with Oraflex, which is 25 before this drug, fialuridine, FIAU, which is before this 167 1 drug, they were sanctioned for failure to report deaths. Can 2 we offer later these documents later on avowal? 3 JUDGE POTTER: We'll keep him and we can examine 4 him on it later. 5 (BENCH DISCUSSION CONCLUDED) 6 JUDGE POTTER: Thank you very much, Doctor. You 7 may step down. You're excused; you may step down. 8 Mr. McGoldrick, do you want to call your next 9 witness? 10 MR. McGOLDRICK: Yes, Your Honor. I'd like to 11 call Doctor John Greist. 12 Doctor Greist, I see. Would you come right up 13 here, Doctor Greist. This is our witness box up here. 14 JUDGE POTTER: Sir, would you raise your right 15 hand, please. 16 17 JOHN GREIST, M.D., after first being duly sworn, 18 was examined and testified as follows: 19 20 JUDGE POTTER: Please have a seat. Please keep 21 your voice up. Would you say your name loudly for the jury 22 and then spell it. 23 DOCTOR GREIST: I'm John Greist, G-R-E-I-S-T. 24 JUDGE POTTER: And answer Mr. McGoldrick's 25 questions. 168 1 EXAMINATION 2 3 BY MR. McGOLDRICK: 4 Q. Doctor Greist, good afternoon. 5 A. Good afternoon. 6 Q. Let me get myself in order here. All right. 7 Doctor Greist, please tell the jury where you're from. 8 A. Madison, Wisconsin. 9 Q. And what do you do? 10 A. I'm a physician, and I specialize in psychiatry. 11 Q. And tell us a little bit about your current 12 position. 13 A. Well, I work at the Dean Foundation for Health 14 Research and Education; I have a number of roles there. I'm 15 also a clinical professor of psychiatry at the University of 16 Wisconsin Medical School, so those are my main roles. 17 Q. Before you go on, you live in Madison now; how 18 long have you lived there, Doctor? 19 A. Since 1965, almost 30 years. 20 Q. And how old are you? 21 A. Fifty-five. 22 Q. Tell us just a little bit of personal 23 information about your family. 24 A. I'm married, have been married 30 years; two 25 children, a 21-year-old junior in college and a 169 1 soon-to-be-14-year-old eighth grader. Family, Indianapolis 2 when I started, and father a physician, mother still living 3 there, two brothers who practice there, family practitioners. 4 So I'm a Hoosier by birth but a Badger by geography. 5 Q. All right. Thank you. Now, tell us a little 6 bit more about this Dean Foundation that you work for, what it 7 does and what you do there. 8 A. Yes. We're a nonprofit foundation, and we 9 conduct research and we provide education to physicians, to 10 lay audiences. Our research is pretty broad based. I'm in 11 the psychiatry side; there is some research going on in 12 internal medicine; in neurology around epilepsy; 13 gastroenterology around ulcers; asthma, things of that nature. 14 But my area is psychiatry, so we do trials of medications, 15 controlled trials of medications. We also have been 16 developing a number of computer measures to keep track of data 17 and to keep track of literature in psychiatry. We've been 18 doing that now for 18 years. I see patients in the controlled 19 trials. I see patients privately, though not very many new 20 ones anymore, haven't had time for that. And those are the 21 main things that we do. 22 Q. We may come back to this in a little bit. While 23 we're at it, tell the jury a little bit about the private 24 practice you do have now, the kinds of patients you see. 25 A. I have a number of patients that I've seen 170 1 through the years and I continue to see them. Don't need to 2 see them very often most of the time, unless they have a 3 flare-up of whatever's been their trouble. So we know each 4 other well and they call me whenever they have trouble, or I 5 see them three or four times a year. 6 Also see patients who come through the 7 controlled drug trials and don't have another physician, and 8 we continue to see them indefinitely. 9 I see a fair number of patients in consultation 10 for other doctors, where I see them a single time just to give 11 them an opinion about what's wrong or what might be helpful in 12 treatment. 13 And I see substantial number of physicians or 14 family members of physicians. They twist my arm more than I 15 like, but I have a hard time saying no to them. 16 Q. When you say you see physicians, you mean you 17 see physicians as patients? 18 A. Yes. 19 Q. And this is in a psychiatric practice? 20 A. That's correct. 21 Q. And you speak of a consultation practice. I 22 suspect we understand that, but could you just make sure you 23 explain that for us? 24 A. Surely. When any physician, I include myself 25 amongst them, has a patient for whom the diagnosis is not 171 1 clear or the course of treatment is not effective, we often 2 turn to another colleague for a second opinion for 3 consultation, and it's in that context that I am able to see 4 patients a single time or perhaps twice for another doctor, to 5 assess what they're having as their problem and to give them 6 my best thoughts about what might be helpful at that point in 7 time. 8 Q. So if another doctor has a patient, that other 9 doctor may, for whatever reason, send that patient to you for 10 another opinion? 11 A. Yes. Correct. 12 Q. All right. What percentage would you say, if 13 you can make an estimate, of your private practice today 14 involves your treating other physicians? 15 A. Well, I think other physicians or their 16 family -- immediate family members, I would say about a 17 quarter of the people I see are physicians or their family 18 members. 19 Q. So is it fair to say in that context that you're 20 kind of a doctor's doctor to that extent? 21 A. Well, to those people I certainly am, and I'm 22 sure I see a higher proportion of physicians and their family 23 members than most psychiatrists do. So, yes, I think that's 24 fair. 25 Q. All right. Now, if you could take the jury a 172 1 little bit through your educational background, sir. 2 A. All right. I grew up in Indianapolis, went to 3 grade school, high school there, Short Ridge High School; 4 graduated in '57. Undergraduate at Princeton University in 5 New Jersey, then back home to Indiana in '61 for medical 6 school. The medical school is in Indianapolis, and I could 7 live at home, and it made all kinds of sense. Had a wonderful 8 education there. 9 '65, I went to Wisconsin, and should have said 10 regarding family, my mother was from Wisconsin, so a little 11 linkage there. Did an internship in internal medicine and 12 then did a year of residency in internal medicine after 13 medical school. That point, the head of medicine said to me 14 that I'd be a better internist if I did one year of 15 psychiatry. That was an age, an era when a lot of us did 16 training in several areas, tried to get broadly trained. 17 So I went over to do that one year and I got 18 really fascinated with it and did a second year of psychiatry. 19 At that point I was four years out of medical school. Then I 20 went back to internal medicine again to finish that, and I was 21 chief resident in medicine at the University of Wisconsin. 22 That was '69 and '70. And after I finished medicine, I 23 returned to psychiatry to finish that residency, that takes 24 three years for each, and that year I did a child fellowship, 25 as they called it, in my last year of psychiatry. So in '71 I 173 1 had finished, and I had done six years of residency training 2 after medical school. 3 Q. When you say a child fellowship, do you mean a 4 residency in psychiatry for children? 5 A. That's correct. Two years of adult, one year 6 for children. 7 Q. How is it that you selected psychiatry to be 8 your specialty, sir? 9 A. Well, I'm sure there are several factors; it's 10 fascinating, first. My father was an internist and a 11 psychiatrist, and when I got to the end of all of this 12 training, I had offers both from the department of medicine 13 and from the department of psychiatry at the University of 14 Wisconsin, but the department of psychiatry offered me more 15 free time, time free from heavy clinical responsibilities, 16 working in the clinic or teaching, to do research. So they 17 gave me six months of time for research for three years, where 18 Medicine was only able to give me two months a year for three 19 years. And if you want to do research, time is the thing that 20 is most important. The money was the same, but the time 21 control was greater with psychiatry. 22 Q. Did you want to do research? 23 A. I certainly did. 24 Q. And have you done research during your career? 25 A. Yes. 174 1 Q. Please explain to the jury what is meant by 2 board certification in a specialty. 3 A. All of the specialties in medicine have boards 4 that certify practitioners after they've finished the 5 residency training process, and usually after they've had some 6 period of experience practicing that specialty. In 7 psychiatry, the board at the time I took the exam required 8 that one be out for two years after residency. So I finished 9 in '71, but I wasn't eligible for the exam until '73. And 10 then you -- in psychiatry, which is what I know best, you take 11 a written examination, and then if you pass that, go on to 12 take an oral examination where various senior experienced 13 psychiatrists watch you interview patients and then discuss 14 with you what you think the diagnosis is and how you would try 15 to help this person. And in my day and age they also had a 16 neurology exam, because it's the American Board of Psychiatry 17 and Neurology, so we did a neurology exam, as well. 18 Q. And are you board certified, sir? 19 A. Yes. 20 Q. About what proportion of people in a specialty 21 become board certified? 22 A. I think now it's half or more. It was fewer 23 when I went through the process. 24 Q. What did you do -- after you completed all of 25 these residencies, medical schools, internships and so forth, 175 1 what did you do next? 2 A. I joined the faculty in the department of 3 psychiatry at the University of Wisconsin, and I stayed there 4 for many, many years. 5 Q. What was your title in the psychiatry faculty? 6 A. I started as assistant professor and was 7 promoted then to associate professor and to full professor. I 8 think in 1980 I became full professor of psychiatry there. 9 Q. So you were a professor teaching medical 10 students and perhaps others about how to be a good 11 psychiatrist? 12 A. That's correct. 13 Q. And, I'm sorry. You may have just said it, but 14 for how long were you a professor teaching there? 15 A. I left the university as a full-time professor 16 in July of '92, so I was there 21 years as a professor. 17 Q. While you were on the faculty of the medical 18 school what were your responsibilities? What were you 19 supposed to do? 20 A. Well, I was supposed to teach medical students 21 and young doctors who had finished medical school and were in 22 psychiatric residency. I had opportunities and some 23 obligation, even, to teach doctors, after they'd finished all 24 of their training out in the community, continuing medical 25 education. Had obligations to see patients to provide some 176 1 care of patients, some service to patients, and also to 2 maintain my skills as a practicing physician. And I had 3 responsibility for research, and that was, as I indicated, a 4 big factor in my choice of psychiatry over medicine in that I 5 had more time available to do research. 6 Q. At least in the broadest way, Doctor, without 7 certainly describing it all, when you say research in 8 medicine, what is it that a doctor is trying to do when a 9 doctor does research in medicine? 10 A. Well, one of the wonderful things about medicine 11 is how broad it is; it's everything in a way, and also how 12 deep you have to go to really get things that are meaningful. 13 I'm what's called a clinical researcher, meaning I'm not 14 interested -- I'm interested, but I'm not trained anymore to 15 do basic biochemistry, neurochemistry, neuropsychopharmacology 16 at a basic level. 17 I'm a clinical researcher. What I want to know 18 and help develop is an understanding of the clinical disorders 19 that we see and the treatments that help people who suffer 20 those. So my focus has been on making diagnoses, studying 21 treatments to see which ones are more effective, which ones 22 have more or fewer side effects. That's been the area in 23 which I have worked in research. 24 Q. Again, we've probably heard this, but the term 25 clinical, clinical researcher, clinical this, clinical trial, 177 1 clinical that, has been heard a lot in this trial. This 2 refers to the clinic and actually seeing patients? 3 A. Absolutely. Clinical means in the clinic or at 4 the bedside, if you look in the dictionary. So this deals 5 with patients, doesn't deal much with test tubes, though 6 certainly we use laboratory reports when they're available. 7 When I was doing medicine, we looked at X-rays and we did use 8 the laboratory, but clinical laboratories is what we used, not 9 basic science laboratories. 10 Q. Now, as you started your practice, first you 11 were on the faculty of the medical school at Wisconsin in 12 Madison? 13 A. Correct. 14 Q. And you also had a clinical practice of your 15 own? 16 A. That's correct. 17 Q. Could you tell the jury what kinds of patients 18 -- as that developed over the years what kinds of patients you 19 saw, what was your practice like? I'm not talking about today 20 now; you've already told us that, but back in that time. 21 A. I understand. When I started, I was doing 22 general psychiatry, including seeing children and adolescents. 23 I was very broad. I didn't restrict my practice in any way as 24 far as psychiatry went. I quit doing internal medicine. I 25 wasn't dealing directly with blood pressure, ulcer, heart 178 1 disease, things of that nature anymore. And I took on all 2 comers. As I say, children in the play room, adolescents with 3 all the turmoil that they have, and adults across the age 4 spectrum. And I dealt with all the kinds of disorders, the 5 mood disorders, manic depressive and depressive; the anxiety 6 disorders, a whole bunch of them; the schizophrenic disorders; 7 the substance abuse disorders; the organic brain disorders, 8 where brain tissue is changed in an identifiable way and then 9 affects the thoughts and the feelings and the behaviors of 10 people. And so I did it all when I started. As time went on, 11 for a variety of reasons I've narrowed my focus. 12 Q. Now, again, I don't want you to take us through 13 all the professional associations that you're a member of, but 14 if you could tell the jury about a couple of those or some of 15 those and what they're like and what their purpose is. 16 A. Well, the associations I belong to basically 17 cover my clinical area and my professional domain. I'm 18 interested in anxiety disorders very substantially now, so I'm 19 a member of the Anxiety Disorders Association of America 20 scientific advisory board and also the Obsessive-Compulsive 21 Foundation scientific advisory board. I'm interested in mood 22 disorders, so I'm a member of the scientific advisory 23 committee of the National Depression and Manic Depression 24 Association. I belong to the American Psychiatric 25 Association; that's the parent organization for psychiatrists. 179 1 And I'm a Fellow in that association, which is something that 2 comes about after a period of time. And if you've done 3 research or made contributions to your community, then you get 4 to be a Fellow rather than just a member. I belong to other 5 research societies, Psychiatric Research Society, a number of 6 specialty things that are more related to my narrow areas of 7 interest. 8 Q. You speak of being a fellow of the APA. 9 A. Yes. 10 Q. What's that again? 11 A. Well, when one finishes -- well, heck, when 12 one's in training you can become a student member of the 13 American Psychiatric Association, and upon completion of 14 membership and before one passes boards or if one never takes 15 boards one can still be a member of the American Psychiatric 16 Association. And then after a minimum of five years, if a 17 member has done things which distinguish him or her in some 18 way, then they can become a Fellow, and they're nominated for 19 things that they've done, either academic things or 20 recognition of their community contributions, if a person has 21 really made a difference in their community. 22 Q. All right. And you're one of those? 23 A. Yes. 24 Q. Do you have any relationship to NIMH, the 25 National Institute of Mental Health, and, if so, explain what 180 1 it is and what NIMH is. 2 A. The National Institute of Mental Health, we 3 abbreviate it N-I-M-H or NIMH, some do, is the federal 4 organization that provides oversight of moneys that Congress 5 approves for certain programs in mental health and also 6 support of research in mental health. So the federal moneys 7 that are used to study psychiatric disorders come through the 8 National Institutes of Mental Health. I do have some 9 associations with NIMH. 10 Q. What are they, sir? 11 A. Well, I'll have to try to explain them. I've 12 had a number of research grants from the National Institutes 13 of Mental Health going back to -- gosh, I'm not sure, I'd have 14 to check my records, but '71, possibly right on up through 15 '88. I've had a Research Scientist Development Award, two of 16 those, each lasting five years, and the purpose of those is to 17 take young investigators and to help them have more research 18 time. So the department of psychiatry gave me six months for 19 research each year for three years, started in '71. And in 20 '74, I was fortunate to get a Research Science Development 21 Award, which continued my opportunity to do research about 22 half time for another ten years, and by then they think you 23 should be pretty established and able to fend for yourself. 24 Also, with regard to NIMH, the way these moneys 25 are awarded, both for research scientist development awards 181 1 and for research is by competitive application. I write up a 2 research grant and send it in, and a group of my peers, 3 colleagues who know about the area, who are senior, who are 4 experienced, who are researchers themselves, then evaluate my 5 application in the midst of all the other applications that 6 have come in in that round of applications, and they have 7 three meetings a year. And not only have I submitted a lot of 8 those, but I've sat on those committees that make those 9 decisions, so that's another part of my association with the 10 the National Institutes of Mental Health. 11 Q. Now, I think the jury has already heard about 12 editorial boards, journals in the field, so we don't need to 13 go into it at any great length at all. But, again, briefly, 14 what are these editorial boards, what do these journals do, 15 and do you have any roles with them? 16 A. Yes. There are a variety of journals, of 17 course, some of them ones that have very small circulations; 18 they may not have much in the way of a review process, may 19 publish pretty much what comes their way or a single 20 individual may make the decision, it's his or her journal. I 21 submit papers to journals and they are peer reviewed, again, 22 much like the process for awarding moneys through NIMH. These 23 papers are sent out to other doctors, other scientists to 24 review. They send the comments back to the editor. The 25 editor then makes the decision whether the paper is acceptable 182 1 at all and, if it is, what kinds of revisions may be needed. 2 So I sit on a number of editorial -- I review papers for a 3 number of journals as a reviewer, and I'm an editor of -- on 4 the editorial board of several journals: Journal of Clinical 5 Psychiatry, and a number of the computing specialty journals. 6 I don't think it's necessary to go into them. 7 Q. The Journal of Clinical Psychiatry is one you've 8 mentioned. You're on the editorial board of that? 9 A. Yes. 10 Q. You've reviewed papers that are submitted to 11 that to see if they're worthy of publication? 12 A. That's correct. 13 Q. And have any of your papers appeared in that 14 publication? 15 A. Yes, they have. 16 Q. Is that one of those journals that psychiatrists 17 are apt to have? 18 A. Yes. I think almost all psychiatrists have 19 Journal of Clinical Psychiatry. 20 Q. Doctor, are you the kind of person who is asked 21 to talk to other psychiatrists, give talks about what's going 22 on in psychiatry? 23 A. Yes, I am. 24 Q. And do you do that with some frequency? 25 A. With more frequency than I like and that my 183 1 family likes. 2 Q. Well, give the jury a sense of how often you 3 do do that and where you're asked to talk. 4 A. For the last five or more years I've given over 5 100 talks a year and I've had a scattered life, which is 6 partly why I don't have as large a private practice anymore. 7 I'm not there; I can't see new patients coming in and provide 8 them the kind of continuity that they need. I give talks 9 across the country: Last week in Greenville, South Carolina, 10 and in Chicago; the week before, in Ann Arbor and Columbus, 11 Ohio; this year, I've been to give talks in Hong Kong, and the 12 Philippines and Malaysia; and on another trip, to Australia, 13 in Sydney and Adelaide. 14 Q. You don't need to give them all. 15 A. All right. I'm sorry. Yeah. But at any rate, 16 it's more than I like, and I've begun to cut back by saying 17 that I'm not going to go anymore to give single talks; I'm 18 going to give two talks on a single occasion or I'm not going 19 to go, and it's begun to help. 20 Q. Who asks you to come to talk to them? 21 A. Well, generally, departments of psychiatry. 22 Q. Departments of psychiatry. Do you mean at 23 universities or at hospitals or what? 24 A. Both. The talk in -- I said Detroit but it was 25 actually Ann Arbor at the University of Michigan. The one in 184 1 Columbus was at a large community mental health center where 2 they had a program on anxiety disorders and had two of us come 3 to speak for an all-day-long presentation. I'm also asked to 4 give presentations by the pharmaceutical industry, and they 5 will arrange to sponsor a talk that physicians sometimes 6 attend. Sometimes they'll provide sponsorship to the hospital 7 or the department of psychiatry to support a talk. 8 Q. Whoever asks you to do the talk, typically who 9 are the audiences? 10 A. Doctors and sometimes laypersons. Because of my 11 interest in anxiety disorders, it often is broader than just 12 psychiatrists, M.D.s. It may also include psychologists, 13 social workers and psychiatric nurses, so those mental health 14 professionals broadly. 15 Q. Do these talks you give have anything to do with 16 something called continuing medical education sometimes? 17 A. They are. Yes. That's what they are. 18 Q. Again, very briefly, what's continuing medical 19 education for doctors and what do your talks have to do with 20 that? 21 A. Well, doctors educate themselves after medical 22 school, after residency training, in part through the reading 23 that they do, in part through attending lectures of people who 24 are doing research and keeping abreast of the cutting edge of 25 what's new and what needs to be shared. Doctors also educate 185 1 themselves by seeing patients. And we begin with patients, 2 continue with patients and end with patients, and we use books 3 and lectures as tools to help us on that course. But 4 continuing medical education is broad; medical lectures are 5 one part of that. 6 Q. Doctor, have you conducted any research 7 regarding psychiatric diseases and therapies or medicines used 8 to treat these diseases? 9 A. Yes, I have. 10 Q. Have you published papers about that? 11 A. Yes, sir. 12 Q. Could you give the jury some sense of how much 13 published work you have in that area? 14 A. Regarding -- sticking to research? 15 Q. (Nods head affirmatively). 16 A. Okay. When we do research, it's not enough just 17 to do it and find the result; it's important to spread the 18 word, to disseminate the results of that research. And over 19 the years, I've written substantial number of papers 20 describing the research work that we've done. I'd have 21 trouble giving you an accurate count of those. It's certainly 22 over 100 papers and probably approaching 200. 23 Q. And have you written -- in addition to your 24 research in that area, written other papers? 25 A. Yes. 186 1 Q. And have your papers been published in 2 peer-reviewed journals? 3 A. Yes, they have. 4 Q. Now, let's turn to today a little bit. I think 5 you told us about your clinical practice. Can you describe 6 for the jury how your research work is allocated today and in 7 the last years, I don't know how many years, five years, 8 whatever is an appropriate time? 9 A. Actually, over the last ten years I've been 10 doing a substantial number of clinical trials of medications; 11 over the ten years it's been about forty or so different 12 trials, so, roughly, four a year that we conduct at the Dean 13 Foundation. I also have continued since 1967 to do research 14 on computer applications in psychiatry and we are continuing 15 that line of work. I have trained specifically in behavioral 16 treatments for anxiety disorders and we do research in that 17 line, as well. 18 Q. Doctor, if it's possible to do this, I'd like 19 you to try to break down for the jury the subject matter areas 20 of your research at around this time in your research life, 21 that is, by medicine or disease or therapy or whatever it is 22 you can break it down. 23 A. Yes. Surely. And perhaps I can bring it back 24 to my broad clinical practice when I started and how it's 25 narrowed substantially. I had an interest in lithium before 187 1 it was ever approved for use in the United States because I 2 had read quite a bit about it in the British publications and 3 began using it then, so I had interest in manic depressive or 4 bipolar disorder. When I got the Research Scientist 5 Development Award, they wanted me to get very intensive 6 research training and sent me to England to work there with 7 Professor Isaac Marx in the Institute of Psychiatry Hospital 8 in London, Sisters of Little Bethlehem, which interestingly is 9 called bedlam, and he was working on anxiety disorders. So my 10 interest seemed to narrow to anxiety and mood disorders, and 11 the pharmaceutical trials that I've been involved in have, I 12 think without exception -- there may be always exceptions -- 13 involved mood disorders or anxiety disorders. Those are the 14 two areas I've worked the most in. 15 Q. All right. Doctor, let me turn to another 16 subject which we've heard a lot about in this trial, but you 17 are a clinician; you see patients. And I think it's important 18 for you to tell the jury and from your perspective what is 19 depression. 20 A. Depression is a horrible illness, and it is an 21 illness; it's not a character flaw. These folks are not 22 weak-willed wimps. It has to have either a mood disturbance: 23 mood is down; they say they're sad, they're blue, they're down 24 in the dumps, they're depressed; or it has to have substantial 25 lessening of interest in important and usually previously 188 1 pleasurable activity for these folks; they lose interest in 2 their work, their families, their children even. Devastating 3 to see that because most of us are so tied to our children. 4 They lose interest in sex, really important things in life. 5 In addition to these two, of which one must have at least one 6 in order to make a diagnosis of depression, there are seven 7 other things that we look at, and these are contained in the 8 classification systems, the Diagnostic and Statistical Manual 9 of the American Psychiatric Association III, III-R and IV. We 10 call them DSM-III, III-R and IV. Usually patients will have a 11 disturbance in their appetite. Most of the time they eat less 12 and lose weight, but some of them eat all the time and gain 13 weight. They have trouble with sleep. Not everyone has all 14 of these, but these are the common things. Usually they have 15 insomnia and, again, there are a few people that sleep all the 16 time; they call it hypersomnia. Folks that get depressed have 17 fatigue, low energy. That usually takes them to see their 18 family doctor or general practitioner for feeling low energy. 19 Doctors examine them and can't find anything wrong. They're 20 not anemic, don't have an ulcer, hard to explain. That's a 21 symptom in depression. They have changes in their activity 22 level. And there are two ways it can go. Psychomotor 23 agitation in which the patient is restless, can't sit still, 24 gets up and paces around, wrings their hands, furrows their 25 brows, they pick at their clothing, they just can't be still. 189 1 And sometimes it goes the other way, psychomotor retardation, 2 in which they are massively slowed down. This isn't that they 3 feel slow, this is that family members say he's become a couch 4 potato. 5 Unfortunately, medicine is never simple. About 6 40 percent of the people have a mixture of agitation and 7 retardation. Self-esteem is dramatically reduced in 8 depression, and the technical question that we ask them is has 9 it gotten so bad that you've felt worthless. And people who 10 are depressed enough will tell you, yep, I feel worthless. 11 Depression interferes with the ability to 12 concentrate, and they'll say, "I can't read the newspaper 13 through. I can't even watch a TV program through. I used to 14 love to read and watch TV." Since they're not concentrating 15 they don't get stuff in; they don't retain it; they aren't 16 tending to it well enough so they begin to forget things that 17 ordinarily they could remember. And if they're of a moderate 18 age such as me, 55, they begin to wonder whether they're 19 getting Alzheimer's disease when they're not, they're just 20 depressed. 21 These individuals unfortunately also have 22 thoughts of suicide, and when all is said and done, people who 23 have major depression, 15 percent of them end their lives by 24 suicide. That's 15 percent. So it's this constellation of 25 things, mood, interests, that are critical, and a total of at 190 1 least five of these nine, they have to be present for at least 2 two weeks and they have to be clinically significant; that 3 means they interfere with functioning or they cause great 4 distress. 5 It's important I think to go beyond this simple 6 description, if I may, because we think, well, somebody's 7 depressed and they get over it and it's done with, and that's 8 not true. The average person who has the first episode of 9 depression will have five episodes in his or her life. Now, 10 surely some have only one, but that means some are going to 11 have many more than five. Depression is a recurrent disorder, 12 and what typically happens -- of course, there are exceptions 13 to this -- is that after that first episode there's a good 14 interval free of depression. The second episode occurs and 15 then the interval is shorter and it gets shorter still, and 16 the depressive episodes get more severe as time goes on and 17 become more resistant to treatment. So we try very hard now 18 to treat that first episode aggressively and then to keep the 19 person in what we call remission, free of depression with 20 whatever treatment has gotten them there. 21 Q. About how common is depression? Do you have a 22 sense of that? 23 A. I do. Depression is very common, and about five 24 percent of the American population is depressed at any point 25 in time. That doesn't mean they're all getting treatment. 191 1 Many of them are thinking that they've done something wrong or 2 that they should just soldier on this way, unfortunately, and 3 they do recover if they don't kill themselves. People do tend 4 to recover from episodes of depression. Unfortunately, about 5 10 percent minimum and some think as much as 25 percent will 6 have a depressive episode starting this process of recurrent 7 depression. So some are between one in ten and one in four 8 Americans has this very difficult disorder. 9 Q. Is this the kind of condition -- well, strike 10 that. 11 How long has this disease existed in man and 12 womankind? 13 A. Through the millenia. And Shakespeare called it 14 well in Hamlet. He said, "Oh, God, God, how weary, stale, 15 flat and unprofitable seem to me all the uses of this world." 16 Dreadful disease. 17 Q. And it occurs to famous people and regular folks 18 and everybody? 19 A. It's an equal opportunity disease. And those 20 who have had heart attacks and depression uniformly say, "I'll 21 take the heart attack." 22 Q. Is there any sense of -- again, you don't have 23 to give us detail on this, but what is the cost of this 24 disease to this country? 25 MR. SMITH: Object to that, Your Honor. 192 1 JUDGE POTTER: Sustained. 2 Q. Doctor -- I'm going to a slightly different area 3 I'm happy to continue. Is this -- 4 JUDGE POTTER: You're about to get out of the 5 background stuff? 6 MR. McGOLDRICK: I'm just about out of the 7 credentials and starting to move into some background of 8 depression. 9 JUDGE POTTER: Let's take the evening recess. 10 As I've mentioned to you-all before, do not permit anybody to 11 speak to you about this case; do not discuss it among 12 yourselves and do not form or express opinions about it. 13 We'll stand in recess till 9:00 tomorrow morning. 14 (JURORS EXCUSED AT 4:00 P.M.) 15 MR. McGOLDRICK: If Your Honor please, I think 16 Doctor Wernicke was going to leave, and he's back in the 17 office. I don't know whether you need him for your documents 18 or you want me to bring him. 19 MR. SMITH: If it's all right with everybody, if 20 I can just submit to the Court these documents at everybody's 21 convenience, I won't require him to come back. 22 JUDGE POTTER: All right. Well, let's get them 23 marked as avowal exhibits. 24 MR. McGOLDRICK: Could I see what we have, and 25 then we've got some argument on a motion. Is there anything 193 1 else you need us for? 2 JUDGE POTTER: Well, you-all are going to have 3 an argument on a motion. 4 MR. McGOLDRICK: Oh, yes. 5 JUDGE POTTER: You-all want to take five minutes 6 before we come back for arguments? 7 MS. ZETTLER: Sure. 8 JUDGE POTTER: Are those the avowal exhibits? 9 Let's get them in. Avowal Exhibits 253, 254 and 255 are 10 entered into evidence. I do need these back because I'll need 11 to identify them. One of them is House Report No. 433-512, 12 dated November -- anyway, it's 1983. The next one is a 13 Federal Register, I guess, a part of a Federal Register 14 published Thursday, October 27th, 1994. And the talk paper 15 dated October 27th, 1994. 16 (HEARING IN CHAMBERS) 17 JUDGE POTTER: Before we get started, let me say 18 something on the record. I say probably a lot of 19 inappropriate things, and a lot of times I don't realize I've 20 said them, but when I do realize it, I try and correct it. I 21 will apologize to Mr. Myers and Mr. Smith, yesterday -- or, 22 Friday when I was making some comment that we ought to put 23 them under oath. It's something that judges say a lot 24 jokingly, what we need to do is put the lawyers under oath in 25 the courtroom. I have the feeling that when I said it Friday, 194 1 it was said more out of something I've heard and said myself, 2 rather than anything in particular in this case. It somehow 3 implies or could imply that somehow I think they've been less 4 than forthright, and I would say that is not the case at all. 5 If anything, if I had to put them on the scale of 1 to 10, I'd 6 put them up in the 9 category as forthright; I just don't give 7 out 10s. So if there was any implication that you-all haven't 8 been forthright, I think you've been very forthright, those 9 particular two people in particular. So I just want to get 10 that. 11 Mr. Freeman, you-all have a motion. What do 12 you-all want to say in its behalf? 13 MR. FREEMAN: Yes, Your Honor. 14 JUDGE POTTER: As I understand it, this motion 15 picks up with the idea, unlikely as you think it will be, that 16 Mr. Smith has prevailed at this stage and the jury has found 17 that Prozac not only caused Mr. Wesbecker to do this, but it 18 was not such an idiosyncratic effect so as to make the product 19 safe; it was enough of a reaction to where it's an 20 unreasonably dangerous product and you-all are liable. So why 21 shouldn't they be allowed to -- tell me why should we stop at 22 that stage. 23 MR. FREEMAN: Well, as painful as it is for me 24 to say that that first eventuality would ever take place; 25 i.e., that Mr. Smith would prevail on these ridiculous claims, 195 1 I did want to point out to the Court the very high standard 2 that the state of Kentucky has -- legislature has taken in 3 connection with even the submission of punitive damages under 4 any circumstances. 5 First of all, I'd like to point out that the 6 evidence must not only be clear, but it must be convincing. 7 Secondly, I'd like to point out that the Plaintiffs in this 8 case have elected to proceed under a theory that Lilly acted 9 with malice. And they have left out in their briefs an 10 essential -- several essential elements to the malice 11 definition. We call the Court's specific attention to it that 12 it is provided that either the conduct which is specifically 13 intended by the Defendant -- is specifically intended by the 14 Defendant to cause tangible or intangible injury to the 15 Plaintiff or conduct which is carried out by the Defendant -- 16 both is the operative word -- both with a flagrant 17 indifference to the rights of the Plaintiff and with a 18 subjective awareness -- and with a subjective awareness that 19 the conduct -- not may but will result in human death or 20 bodily harm. Now, the operative words there is "will result 21 in human death or bodily harm," and the first one as the Court 22 will look at shows specific intention. And in this record 23 nothing -- 24 JUDGE POTTER: All right. Mr. Smith will have 25 to concede that Lilly didn't set out to hurt people. 196 1 MR. FREEMAN: All right, sir. If he concedes 2 that, then he must prove by documents and/or witnesses that 3 Lilly was flagrant; that it was flagrantly indifferent to the 4 rights of the Plaintiff; that is, didn't care at all, and with 5 a subjective awareness, that is, it knew -- it knew the 6 subject that such -- its conduct, what it was doing will 7 result in human death or bodily harm. It's not a matter of 8 "may," it's "will," and that we knew that that would result 9 from the development of Prozac. 10 Now, in that connection, they make claims in 11 their brief which we have addressed A through L, and we start 12 out with the proposition of the growling cats and the dogs, 13 and we move from that point onto a number of other situations. 14 But let me say to the Court what the record is in this case. 15 There's not a slightest conflict that the tests, all of them 16 that they talk about with respect to the dogs and the cats, 17 are toxic tests, where it is the intent of the investigator to 18 make these animal sick as hell, if you'll excuse the language. 19 They are dosing them sometimes 15 and up to 40 times of their 20 body weight, which is a tremendous amount more than any human 21 under any circumstances would ever do. So they're trying to 22 get them as sick as they can to see what effect it will have 23 on their organ systems. And, obviously, as one of the 24 witnesses pointed out out here, when they make these animals 25 so sick, Doctor Ray Fuller said, the animals are reacting to 197 1 their illness, that is feeling so bad. For example, with a 2 rat, they make them nauseated, but a rat can't throw up. So 3 obviously a rat is going to become nervous and intent and 4 things of that kind. And the same is true in connection with 5 when they make these dogs and cats so sick with the cats not 6 being able to urinate for a period of three or four days. 7 Obviously if they're not able to urinate, they are very sick 8 and are likely absolutely to hiss and growl. So to take that 9 and make a jump to humans who are not given these toxic doses 10 in the first place, is certainly something that does not show 11 any intent to hurt anyone. 12 The second set of documents or the second 13 documents that they refer to are the documents that talk about 14 testing in human patients again to demonstrate the stimulant 15 effects of the drugs, including insomnia, agitation, suicidal 16 ideation and psychosis. Now, the reports that they are 17 talking about in those instances are -- were done in the late 18 '70s, according to my best recollection, and it was never 19 concluded in any of those studies that the medication itself 20 were causing these because each of those conditions are, as 21 you just heard, a symptom or an outcome of being depressed. 22 So certainly to my mind those don't point out anything in 23 connection with any sort of willful act when you are treating 24 something and you see it continue to occur. Like if you 25 continue to cough when you have a cold, you don't blame Contac 198 1 for not curing your cold because it's a part of what Contac is 2 trying to treat. 3 The next set of documents, they tend to want to 4 emphasize that Lilly structured its clinical trials to mask 5 the effects by excluding patients at risk of becoming violent 6 on the drug such as suicidal patients and patients with 7 schizoaffective disorder. Now, it's absolutely clear from the 8 evidence and there's no conflict in the evidence about this 9 that Lilly had two sets of clinical-type trials. We had 10 outpatient trials and we had inpatient or in-hospital trials. 11 All of the witnesses have testified that it would be unethical 12 to take a patient who had a serious risk of suicide and put 13 him in a trial, particularly when you were going to be 14 treating him, randomizing these people for placebo to 15 comparitor drug to Prozac. Particularly at that time you 16 wouldn't want to do that because you wouldn't know whether 17 Prozac was going to be effective. That's what you're trying 18 to find out in treating this particular disease, and you 19 certainly wouldn't want to put a patient on a placebo or sugar 20 pill that had a risk of suicide. So what Lilly did in that 21 incident was most responsible in that it conducted trials both 22 for outpatients and inpatients and there were three large 23 trials done for inpatients; one being a multicentered one done 24 in Germany and two being here. So, again, we say that 25 allegation has no merit in connection with submitting any 199 1 malice toward the public or flagrant disregard for the public. 2 The next contention that they make is that Lilly 3 altered and amended their clinical trial Prozac to allow for 4 the reduction of dose of Prozac and for the coadministration 5 of sedative drugs which mask the stimulant effects of Prozac. 6 Now, let's look at what we're looking at here. A lot of talk 7 has been made about this, but all of the evidence shows that 8 no concomitant medication is ever given until what happens, 9 and that what happens is when the patient comes in and says to 10 the doctor, "I can't sleep at all, I need something to help me 11 sleep." The way it has been presented by the Plaintiff in 12 their briefs and otherwise one would think that if we had 200 13 people on a trial so as to mask how it would come out, we'd 14 start off and we'd give them Prozac, we'd give them a sedative 15 and we'd give them -- and randomize them and then give the 16 placebo, but that's not the case at all. Those portions of 17 the patients that become jittery or those portions of the 18 patients that can't sleep, then under certain circumstances 19 are given a concomitant medication and that only would be 20 ethical and responsible to treat that other condition that 21 presented itself to those people that are so sick. 22 The next allegation is that Lilly has knowingly 23 hidden evidence of Prozac's propensity for causing violent 24 behavior. Even scientists working behind the scenes at Lilly, 25 they allege, and Lilly's own clinical investigators have 200 1 knowledge of many instances where they themselves became 2 violent, demonstrated by patients that were on Prozac, and 3 that's simply not so. In connection with this, they point to 4 Heiligenstein's memorandum wherein all he says is, "Doctor 5 Leigh Thompson, be cautious," it doesn't say that it is going 6 to cause increased violence or anything of that, saying, "Be 7 cautious in what you say to the board because this is fuzzy," 8 and I think we have to look at the time that he said it. He 9 had just had a report of the shootings down here; we had just 10 heard about all of those things and about the same time they 11 were bringing into play all of the Church of Scientology 12 business and all of that sort of stuff that we were dealing 13 with. Writing a memorandum about being cautious should 14 certainly not be a ground to say that Lilly was being flagrant 15 or had malice toward the patient population, but simply that 16 we were exercising caution in what we were doing and we 17 continued to study the thing right on up through and up till 18 today up till the FDA found that there was no credible 19 evidence that it did cause any of these things that they say 20 we were trying to hide, and the FDA has looked at all of that. 21 I have not seen one document or one set of questions or 22 anything that they can show that we have not told the FDA 23 about in some form. And they complain about how we told them 24 about it, but they can't point to one single thing that we 25 haven't informed the FDA fully on. 201 1 The next allegation is with respect to the 2 German government, and we have about beat that subject to 3 death. First of all, in Plaintiffs' Exhibit No. 67, and in 4 that great big exhibit one hundred and whatever it is, with 5 all the million pages that were passed around in the courtroom 6 this morning, not only has the FDA been informed of the BGA's 7 precise questions and the precise answers that they have 8 given, it is in exactly the same version on those two 9 occasions. Not only have they done that, but they have 10 summarized it in other documents that have gone to the FDA 11 pointing out all of this business about sedatives and things 12 of that kind and activation. 13 Now, the thing that really befuzzles me about 14 the whole situation, and we've quoted the whole thing in the 15 brief, is that Mr. Wesbecker was on what their experts said 16 was a sedative and he had it in his bloodstream at a 17 therapeutic level at the time the autopsy was done some 18 several hours after these shootings had occurred, and it is 19 amazing to me that they can claim that because Doctor Coleman 20 was doing precisely what they criticize us for doing in the 21 tests, that is, for allowing a patient that has insomnia to 22 take a sedative, that Mr. Wesbecker at the time and place was 23 in fact on one that was prescribed by Doctor Coleman and he 24 had it in his bloodstream at a therapeutic level. 25 And Mr. McGoldrick has just gone into the next 202 1 section in terms of the calculations on the 16 patients as 2 compared to the 1 and the 0, you'll remember that testimony so 3 I don't think there's any need for me to go back over that 4 because that's exactly what the situation is in connection 5 with those allegations; that they are basically, i.e., from a 6 statistical point of view when you take into account the 7 patient treatment time equal in the number of suicides or 8 suicide attempts that have been attempted or acted upon. 9 H, the next one, alleges that in response to the 10 issues raised by the German government, Lilly hired so-called 11 experts to review the suicide attempts reported to 12 psychiatrists during the clinical trials. Quoting further, 13 they allege, Lilly's goal in this exercise was to cull out as 14 many suicide attempts as possible; however, even though these 15 so-called experts reduced the number of suicide attempts from 16 14 to 5, they also found some remaining attempts causally 17 related to the use of Prozac. Now, to suggest that the head 18 of the department at the University of Iowa, Doctor Winniker, 19 is going to go in and do something dishonest, and that just by 20 saying that they're going to be able to carry that over into a 21 punitive damage allegation is, to my mind, absurd. In the 22 first place, they went to each one of these things and 23 thoroughly investigated them to see whether or not they had 24 made any suicide attempt and if they had not attempted suicide 25 in the investigation that was done in depth, those people were 203 1 removed. And only on one area did they say that it was 2 possibly -- not probably -- possibly causally connected and 3 that's the phrase that they keep trying to make it probably. 4 And in Doctor Woolson's notes, who worked on this project with 5 Doctor Winniker, he says and we quote it here that, I continue 6 to be surprised as to the low number of suicide attempts in 7 the studies that they looked at. And all of these numbers, 8 that is, the gross numbers and all of this was supplied to the 9 FDA for their own perusal so they could make their own 10 judgment about it. 11 Then the next allegation is Lilly purposely 12 failed to perform clinical trials that would better define the 13 patient population most likely to become violent on Prozac. 14 Question after question keeps being asked about that subject, 15 and certainly that can't be the subject of any punitive damage 16 allegation that will get you to a jury, and the reason for 17 that is you get 8,000 people in these studies. I have this 18 many people in this room and I couldn't tell you at any 19 particular stage if all of them were depressed which one of 20 them might become violent, but if I look at 8,000 people and 21 give it to 8,000 people I can make a real judgment as to 22 whether or not Prozac causes somebody to become violent 23 because I've got such a large patient population that I can 24 make that judgment. I couldn't go out and there's no way in 25 the world to pick out what group of patients might fall into a 204 1 category of becoming violent. That's an impossible task, so 2 certainly we're not charged and should not be submitted to -- 3 this should not be submitted to a jury in connection with 4 something that is not even possible for us to do, that is, to 5 predict what groups of people might conceivably become 6 violent. And certainly Lilly has not done that and cannot do 7 that and there's no way to do that. But we have done huge 8 studies and there have been 15 million people on the drug and 9 you don't see people running around shooting everybody. If 10 you listen to the Plaintiff, we'd have half of the people in 11 this country dead because of the violent nature of what Prozac 12 would do to the people that were taking it, and that simply is 13 not and has not happened. So we say that that certainly can't 14 get them to the jury on that issue. 15 They also in that section talk again about not 16 testing it on people that had multiple illnesses. In other 17 words, not particularly selecting out a group that have 18 schizoaffective disorder and are depressed and trying to test 19 it with them. Though some of the people in the studies were 20 shown to have schizoaffective disorder, they were not 21 specifically pointed out and we have no reason to ever think 22 that it was going to be used for schizoaffective disorder, and 23 certainly that is not something that reasonable minds couldn't 24 differ on. 25 The next section is that the FDA asked Lilly to 205 1 conduct clinical trials on Prozac specifically designed to 2 look at the incidence of violent behavior, including suicide, 3 in patients on Prozac and this is where we get into the 4 controversy about the time frame. First of all, that was done 5 before they had the advisory committee meeting. Secondly, 6 after the advisory committee meeting they found that there was 7 no credible evidence that any of this ever occurred, anyway, 8 and you have the same problem. They got a protocol up. They 9 went around and they talked to investigators and they say, we 10 don't know, we don't have any patients that have ever seen the 11 Teicher syndrome and there were only six for him. We don't 12 have enough patients to test that have become violent while 13 they've been on Prozac. There's no way for us to do any 14 rechallenge. That's what it is. They're trying to get 15 somebody that has been suicidal on Prozac or has had 16 violent-aggressive behavior while on Prozac and then 17 rechallenge them to see if they do it again. The phenomenon 18 had not been seen and that's why the advisory committee found 19 there was no credible or believable evidence that that 20 occurred in the patient population. 21 Now, Doctor Tollefson correctly told the next 22 allegation that the study of the phenomenon had commenced 23 because we had started; we had prepared the protocol, we had 24 sent it to the FDA and we had interviewed investigators to 25 determine if that could be done when they had the meeting down 206 1 there. 2 The next section of documents is an allegation 3 every time an issue has been raised regarding violent behavior 4 and the use of Prozac, Lilly has carefully and purposefully 5 avoided presenting an analysis of its own DEN databases. All 6 of these adverse events are required by law to be reported to 7 the FDA, and then they make the statement that is 8 unbelievable: Failure to report these adverse events is a 9 felony, a felony which Lilly has been convicted of before. 10 First of all, Lilly was found guilty of a misdemeanor for not 11 failing to report but reporting late ten events in connection 12 with Oraflex and one other misdemeanor. It was not ever found 13 guilty of any felony. Now, Lilly has published on this 14 violent-aggressive behavior through Doctor Heiligenstein two 15 papers on the subject. The DEN database cannot be similarly 16 analyzed because there is no denominator, and the Court's 17 familiar with what I'm talking about. For example, if we had 18 15 million patients on the drug, that's an estimate, we can't 19 say that that is absolutely accurate to the -- down to the 20 last notch because we just have to estimate that because we 21 know that, for example, in 1993, I gave the number earlier, so 22 many prescriptions were written but you couldn't tell whether 23 the same patient maybe had 10 prescriptions in a year or 1 24 patient had each of the 10 prescriptions that were written. 25 So there is no way to be able to tell what the denominator in 207 1 the DEN would be in making any real calculations from it. You 2 can only do sort of a real calculation from that. You can do 3 sort of an epidemiological study from that and be able to see 4 that there's no pattern there. 5 Certainly they have not shown that we acted with 6 any intent; that there's clear or convincing evidence that 7 Lilly has set about to harm any individual plaintiff; 8 certainly there's no conduct that any of those things arise to 9 that is flagrantly indifferent to the rights of the Plaintiff 10 and with awareness -- subjective awareness on Lilly's part 11 that the conduct will result in human death or bodily harm. 12 And we say, Judge, as a matter of law, we're entitled to 13 justice at your hands and an order in our favor on this motion 14 for summary judgment. 15 JUDGE POTTER: Mr. Smith or Ms. Zettler? 16 MS. ZETTLER: Judge, as you know, under 17 Steelvest, the burden is on Lilly to prove that there is no 18 general issue of material fact with regards to punitives in 19 this case, and I think that Mr. Freeman has done a pretty good 20 job of setting out for the Court what the facts are and the 21 contentions are from both sides. 22 Just to recap what our position is on this, we 23 believe we've shown so far in this case that Lilly knew very 24 early on animal studies and very early human studies, as 25 testified to by Nancy Lord, that there were problems with this 208 1 drug causing stimulant profile in various people, that some of 2 these people, depending on in some parts their underlying 3 condition, were caused to become very seriously agitated, 4 psychotic and suicidal on this drug. In response to those -- 5 the early indications, this company did nothing but try to 6 cover up that profile of the drug and they did it in a number 7 of different ways. First they allowed for the concomitant use 8 of medications, specifically benzodiazepines, and specifically 9 admitted protocols, which we have shown to control agitation 10 -- to allow for this to control agitation. In addition, they 11 allowed for the reduction of the dosage in those situations to 12 control agitation. When the German government raised the 13 issue, I believe we've shown not only that Lilly did not 14 inform the FDA but they did everything they could by 15 contacting directly and indirectly members of the German 16 government to try to manipulate them and to try to convince 17 them or somehow get them to approve this drug without 18 contraindications like the BGA originally wanted in people who 19 were suicidal and agitated and without, they were hoping, the 20 recommendation for the use of concomitant sedative. We 21 believe they were successful because of this influence -- 22 undue influence on government officials in the BGA on keeping 23 this drug from being contraindicated in use for people who 24 were agitated or suicidal, but what they were not successful 25 in doing was keeping the BGA from recommending a concomitant 209 1 sedative in those patients who were suicidal or agitated. 2 This was never told to the FDA. 3 I think again we've established fairly clearly 4 through Doctor Wernicke today that when the FDA specifically 5 raised questions as to the damaging effects, what they meant 6 was the increased risk of suicide and the agitating effects of 7 the drug. This company told the FDA that they did not know 8 what the BGA was talking about. This issue was never told to 9 the FDA at either the advisory committees that were held on 10 this drug and it has never been told to the American doctor or 11 the American patient. 12 As far as the specific issue of schizoaffective 13 disorder, Doctor Slater testified that some of those early 14 patients who had psychotic worsening or suicidal ideation 15 early on in the clinical trials, it was his belief that these 16 patients were schizophrenic or schizoaffective. Literally 17 every Lilly witness has testified that this company has never 18 done a specific clinical trial on schizoaffective patients. 19 Now, Doctor Greist will testify on 20 cross-examination that it is appropriate or it was appropriate 21 for this drug to be given to Joseph Wesbecker under the state 22 of the package insert, by Doctor Coleman. Our contention is 23 that if they hadn't this -- at best if they hadn't tested this 24 drug in schizoaffective patients which they knew had the 25 underlying depressive condition, they should have 210 1 contraindicated the use of that drug in the package insert. 2 What is even worse in this case, Judge, is that the drug was 3 not only not tested, very early on they had some bad 4 experiences with these types of patients. They never tested 5 it specifically. They never told the FDA about their 6 suspicions and then they used concomitant medications who 7 under their protocol should not have been let in. 8 The use of concomitant medications, their 9 argument is it was done across the board. Our argument is 10 these guys, you know, may have been trying to cover up 11 something but they're not dumb. They're not going to just 12 give the concomitant medications to the people on fluoxetine. 13 The problem with using concomitant medications specifically 14 for controlling agitation, which is what they admitted their 15 protocols to do, is that you have somebody who's agitated, you 16 keep them from getting worse, so we don't know what would have 17 happened to these patients if they had continued on with their 18 agitated course without the use of concomitant medications. 19 As far as whether or not there's been a 20 subjective -- and frankly, Your Honor, we don't concede that 21 there was no subjective awareness that the conduct would 22 result in death and bodily harm. 23 JUDGE POTTER: I think in this kind of case if 24 you prove they did everything you said they do, the jury won't 25 have any trouble finding that they knew that people could get 211 1 hurt from not following those protocols and jacking things 2 around. His real thing is that you won't be able to show that 3 they fudged it, cloaked it. Mr. Freeman would admit that if a 4 guy doing a drug hides the results, he knows that people are 5 going to get hurt because of that. I mean, that's not the 6 thing. His thing is that you won't be able to convince a jury 7 or there's no evidence from which a jury could reasonably find 8 that Lilly did anything improper. Go ahead. 9 MS. ZETTLER: Okay. But I'm just saying that, 10 you know, there was some talk about us conceding that there 11 was no subjective orders. I don't think that we're going to 12 concede that, mostly because this company has a history of 13 this kind of conduct. In fact, before or actually during the 14 same time that this drug and NDA on this drug was being filed 15 was when they got caught not reporting deaths that occurred 16 with their drug Oraflex. In that case they did exactly what 17 they're doing here. They said it was a part of the underlying 18 disease process or it was something that was related to the 19 underlying condition of the patients that were getting 20 Oraflex. The same thing they did with this FIAU drug that 21 they just got nailed on. It's a hepatitis B drug. People 22 were becoming very will and toxic on the drug. 23 JUDGE POTTER: So the 1994 thing is a whole 24 new -- 25 MS. ZETTLER: It's a whole new thing. Now, I'd 212 1 like to point out that both occasions, including this most 2 recent one, the FDA has redone their regulations to require 3 stricter reporting adverse events and stricter because of 4 Lilly's conduct, specifically because of conduct of Lilly. 5 But, I mean, I think we're going to be able to show that this 6 is a company -- maybe you will or will not let us do it during 7 this part of the trial but certainly during punitives, that 8 this is a company with a history of flagrant disregard for the 9 safety of the potential patients that are getting their drugs. 10 I think to sum it up, we believe that there are 11 numerous, numerous issues of genuine issues of material fact 12 that exist in this case as far as punitive damages goes and 13 they have not reached their burden of showing that no genuine 14 issues of material fact exist under Steelvest. 15 JUDGE POTTER: I'll get you something fairly 16 shortly. And, Mr. Freeman, I don't want to make it sound like 17 you're necessarily going to lose, but since you brought it up, 18 I want to remind you-all of an issue way down the road 19 somewhere is whether or not the word clear and convincing, if 20 you ever get to that stage, goes in instructions. You know, 21 the jury's instructed you must find by clear and convincing 22 evidence or whether it is some kind of threshold issue that 23 the Court makes, yes, the evidence is clear and convincing, 24 therefore it goes to the jury. And I had a lot of time with 25 that issue four or five or six years ago and, as I understand 213 1 it, there's a split around the country and you-all might -- 2 that's just something that occured to me listening to Mr. -- 3 MR. FREEMAN: If everything she says is true, 4 which it is not, what she is doing is taking a document and 5 making an argument. She is coming from a document and saying 6 this is what it means, when the witnesses say, no, this is 7 what it means. If you take the documents by themselves, by 8 themselves without the argument, this does not rise to any 9 flagrant conduct and it certainly doesn't rise to the 10 definition of malice as set forth on there and it is not clear 11 and convincing. 12 JUDGE POTTER: Well, as I say, I'll let you-all 13 know something. Let me see if there's anything else. 14 MS. ZETTLER: Can we get a list for the 15 witnesses for the rest of the week? 16 MR. STOPHER: I'll get it to you. 17 JUDGE POTTER: I saw somebody pointing to a 18 list, I thought you had that. 19 MR. STOPHER: We need to get these depositions 20 resolved. 21 MR. SMITH: Let's get resolved what we're going 22 to do in trial testimony before this jury the rest of the 23 week. 24 MR. FREEMAN: First of all, we've got Greist on 25 now. Tomorrow there will be Doctor Tollefson after Mr. Greist 214 1 is through. 2 MR. SMITH: Doctor Tollefson? So that should 3 take you through tomorrow? 4 JUDGE POTTER: Let's get through the rest of it 5 because I have thrown away the piece of paper, because I think 6 last Friday we had five or six people in order, didn't we? 7 MR. FREEMAN: When I gave them this was last 8 week, you-all remember. 9 MR. SMITH: As I understand it, your witnesses 10 end with Tollefson and it's going to end probably tomorrow 11 with Tollefson. I never know who's coming up. 12 JUDGE POTTER: Give him the rest of the week, 13 Mr. Freeman or Mr. Stopher. 14 MR. STOPHER: I'll be glad to in the morning. I 15 don't know right now. 16 MR. SMITH: That's not acceptable. 17 MR. STOPHER: Well, I want to read the 18 depositions of several of these people that have been pending, 19 Judge, since October the 26th. 20 MS. ZETTLER: You've got David Fewell, you've 21 got Mary McCarty, you've got Mike Shea. I've got two 22 outstanding ones I will get you, I will try to fax them to you 23 tonight. 24 MR. STOPHER: I want to read some of those 25 depositions. Shea's deposition is pending. I forget. 215 1 There's a list of about eight or nine of those, Judge, that 2 I'd like to get done. 3 JUDGE POTTER: Pick them in the order you want 4 to do them in. 5 MR. STOPHER: I guess -- here's the list. James 6 Croft, Judge, is the one that has been pending since October 7 28th. 8 JUDGE POTTER: What order do you want to take 9 them in? 10 MS. ZETTLER: That's the gentleman who they have 11 not proven to us is unavailable to us, Judge. 12 MR. STOPHER: Yes. I have a letter from his 13 doctor, Judge, another letter. 14 JUDGE POTTER: This is the guy that sent the 15 jury letter? 16 MR. STOPHER: Right. Here's a copy of that 17 letter. 18 JUDGE POTTER: Who is Mr. Croft? 19 MR. STOPHER: He is a pressman, Judge. 20 JUDGE POTTER: And what is he there to prove? 21 MR. STOPHER: History of threats. 22 MS. ZETTLER: He's not going to say anything 23 different than anybody else has said so far, Judge. 24 MR. STOPHER: Well, I disagree with that. 25 JUDGE POTTER: Wait. Wait. 216 1 MS. ZETTLER: Frankly, we object to this 2 statement, because he does not -- I mean, this looks like the 3 guy went in and said, "I don't feel like going to court, 4 please give me a letter." 5 JUDGE POTTER: All right. Okay. All right. If 6 you can't have Croft first, who do you want the deposition 7 order? 8 MR. STOPHER: Judge, we'd like to read the 9 deposition of David Fewell, Donald Jackson, Richard Keilman. 10 We will call some live witnesses. I recall off the top of my 11 head Charles Ganote, and I forget who else, Judge, I'll have 12 to fax that out tonight. 13 JUDGE POTTER: All right. But you don't want 14 Shea in this initial group? 15 MR. STOPHER: Well, it depends on when this 16 stops. If I've got a day and a half this week, Judge, I may 17 get to Shea. 18 JUDGE POTTER: All right. So have you given 19 them your objections on Fewell, Jackson, Keilman? 20 MS. ZETTLER: Donald Jackson I thought we did 21 live. 22 MR. STOPHER: Hunh-uh. 23 MR. MYERS: We did a guy named Danny Jackson. 24 MR. STOPHER: That was Danny Jackson, the 25 gunsmith. 217 1 MS. ZETTLER: Okay. Well, Keilman and Fewell 2 they have, and Shea they have. Jackson I'm not sure if they 3 have or not because, frankly, I thought that was -- I know I 4 saw a deposition, I know I read a deposition. 5 MR. MYERS: The Court has already ruled on 6 Keilman. We have objections for Fewell and Jackson which need 7 to be ruled on. We have objections for Shea which need top be 8 ruled on. We don't have objections for McCarty, Rothenburger 9 and Rakow and Croft. 10 MR. STOPHER: The ones in the list of 11 importance, are Croft, Fewell, Jackson, Keilman, Shea and 12 Rakow. 13 MS. ZETTLER: Judge, we're going to have to take 14 up Rakow. 15 JUDGE POTTER: Who is Rakow? 16 MS. ZETTLER: Rakow -- Rex Rakow is the expert 17 that we hired against Hall Security. Now, nobody has 18 designated -- Lilly has not designated him as an expert in 19 this case; we have not designated him against Lilly as an 20 expert in this case. I mean, once that issue was resolved by 21 settlement, he was not -- 22 JUDGE POTTER: Is this the guy that's going to 23 say he should have pulled the fire alarm? 24 MS. ZETTLER: Yeah. 25 MR. STOPHER: Among other things. 218 1 JUDGE POTTER: What are the "among other 2 things"? 3 MR. STOPHER: He says the security was 4 inadequate and that many people's lives could have and should 5 have been saved if they had had adequate security. 6 MS. ZETTLER: He absolutely does not say that. 7 MR. STOPHER: Yes, he does. 8 JUDGE POTTER: Wait just a second. There is a 9 looming problem here, and I guess I might as well bring it up, 10 is a lot of this expert testimony addresses a standard that is 11 not the legal standard, or at least I'm not convinced at this 12 point it's the legal standard. It's my understanding, and I'm 13 having -- trying to do a Lilly research on it -- that an 14 employer has a very limited duty to protect his employees from 15 the criminal acts of others. And so the fact that some guy 16 that comes in and testifies that, you know, if I were going to 17 put in good security or I were going to put in proper security 18 or I were going to put in excellent security I would do thus 19 and so, I may have a problem with that in the sense that the 20 legal obligation of Standard Gravure is a lot lower than 21 adequate security, you know. My -- I haven't thought it 22 through, but when we call these people, somebody I guess needs 23 to be in a position to convince me that Standard Gravure had a 24 duty to provide whatever level of security, adequate security 25 that this gentleman is going to testify how you achieve that. 219 1 Maybe I'm not putting it very well but... 2 MR. FREEMAN: Use ordinary care to provide 3 security is what the -- 4 JUDGE POTTER: Well, I don't know if they have 5 that. I mean, that's an issue that maybe somebody needs to 6 address with me, is show me a case that says this is where it 7 is. But let's go down the -- let's just plan on this. 8 They've given you the -- you give them their witness list, you 9 and Mr. Myers and I will start at 7:30 tomorrow and get 10 through these people in the order that they think they need 11 them. 12 MS. ZETTLER: We've gotten Keilman done. You've 13 gotten Fewell and you've gotten Jackson, right, and Shea. So 14 what would you like to do in the morning? 15 JUDGE POTTER: No. Shea hasn't been ruled on. 16 MS. ZETTLER: Right. You've got to rule on 17 Fewell, Jackson -- I've given them my objections to Fewell, 18 Jackson, Keilman, Shea, and we'll have two or three more this 19 evening. 20 MR. MYERS: The Court's already ruled on 21 Keilman. That's done. 22 MS. ZETTLER: Right. So I guess what I'm asking 23 Larry is which ones does he want to go over in the morning? 24 JUDGE POTTER: Yeah. Right. 25 MR. MYERS: I guess Fewell, Jackson and Shea, 220 1 since those are the ones that are done. 2 MR. SMITH: Does that mean there's not going to 3 be any live witnesses this week? 4 MR. STOPHER: Oh, no. I'll put in some live 5 witnesses, and I'll telefax them to you tonight. I know 6 Ganote is on the list; I just can't remember who else is on 7 there. 8 MS. ZETTLER: Now, can we get an idea of order 9 as far as if he's going to intersperse depositions in all 10 these and stuff. 11 MR. STOPHER: When I telefax these to you I'll 12 put in the order in which I intend to call them both live and 13 in depositions. 14 JUDGE POTTER: Let me ask you this: Is this 15 collection of experts, are you going to call all of them that 16 you revealed? 17 MR. FREEMAN: We're going to call the ones that 18 I've indicated to the Court and to Paul that we were going to 19 call. 20 JUDGE POTTER: Well, just for my planning let 21 me -- 22 MS. ZETTLER: He means besides the group, like 23 Granacher and Fox and -- 24 MR. FREEMAN: Yeah. Sure. Sure. 25 JUDGE POTTER: Well, we've got Greist. I mean, 221 1 you-all at this time are planning to call all the people 2 listed on expert, as far as, you know, the... 3 MR. STOPHER: No, I don't think all of them are 4 going to be called. 5 MR. FREEMAN: Not all of them, Judge, no. 6 JUDGE POTTER: Okay. Because, like, what is it, 7 Rothschild seems like he -- 8 MR. FREEMAN: He's not going to be here. 9 JUDGE POTTER: I've got "will be the same." 10 He's Mr. Greist; right? How about Granacher and Schwab? 11 MR. STOPHER: Right. They'll be here. 12 JUDGE POTTER: Somehow I thought they were kind 13 of the same. 14 MR. SMITH: What about Winsdell and Mercer. 15 MR. STOPHER: Mercer for sure. I don't think 16 Winsdell will be necessary. 17 JUDGE POTTER: Okay. 18 MR. SMITH: You got any idea, Ed, how many more 19 of the pressman types? 20 MR. STOPHER: Three or four. Three or four. 21 JUDGE POTTER: Let me do the other thing. 22 MS. ZETTLER: We'll be here for two years. 23 JUDGE POTTER: Yeah, because that's the -- 24 MR. MYERS: I think the only Lilly person left, 25 Judge, and we don't intend to call him this week, is Doctor 222 1 Thompson; we may or may or may not recall him. 2 JUDGE POTTER: All right. You've got Fuller, 3 Tollefson, Wernicke and Leigh Thompson again maybe; is that 4 it? 5 MR. MYERS: Yes, sir. 6 JUDGE POTTER: So that leaves you with Tollefson 7 as your only one out of this list. I mean, obviously some of 8 them have already testified through their depositions but it 9 isn't as bad as it seems, because I'm looking ahead and I see 10 all these experts, plus I see that. 11 And you-all have a disagreement about your own 12 witness -- what is his name? 13 MS. ZETTLER: Rex Rakow. 14 JUDGE POTTER: And you're planning to read the 15 deposition or call him? 16 MR. STOPHER: No. He's in Indianapolis or in 17 South Bend, Indiana, at the University of Notre Dame and is 18 beyond my ability to call him. I want to read his deposition. 19 JUDGE POTTER: He's not beyond your ability to 20 call him. 21 MR. STOPHER: Subpoena? 22 JUDGE POTTER: Checkbook. 23 MR. STOPHER: No. He's their expert; I'm not 24 about to do that. But in any event, that deposition we 25 definitely want to read. 223 1 JUDGE POTTER: How long is it? 2 MS. ZETTLER: It's long. 3 MR. STOPHER: It's not very long. It's about -- 4 I'm going to recall from my memory about three hours, Judge. 5 And I would expect that we designated most of it, but it 6 respectfully is right on point and it was in support of their 7 claim against a co-defendant. 8 MS. ZETTLER: Judge, I think maybe in this case 9 it might be, and this is just a suggestion a good idea for you 10 to read that deposition because I don't believe that Mr. Rakow 11 ever does establish what Mr. Stopher appears to feel like he 12 establishes. 13 JUDGE POTTER: I read it briefly because Hall 14 had a motion for summary judgment, and I kind of skimmed it 15 and all I got out of it was that Mr. Addams -- Aabrams should 16 have pulled a fire alarm while he was frantically running 17 through the building. 18 MR. STOPHER: That's in there, but there's a 19 whole lot of other information in there, particularly, Judge, 20 I think the portion that perhaps the Court read was the 21 portion taken by Mr. Carroll, who was representing Hall 22 Security. I cross-examined Mr. Rakow on the broader issues 23 than precisely what Hall Security did wrong, and what he said 24 was is that Standard Gravure in his opinion violated the 25 standard of care in the industry for that type of facility; 224 1 that if they had had adequate security or even reasonable 2 security for that type of facility that most if not all of 3 these lives and the injuries would have been prevented and 4 avoided. So I do not think that the statement that I've 5 mischaracterized that deposition is at all accurate. 6 JUDGE POTTER: You read these things from 7 different points of view. When you're dealing with a motion 8 for summary judgment you read it as enough to where they get 9 past that. 10 MR. STOPHER: I think the Court determined that 11 there were genuine issues of material fact with regard to the 12 claim of negligence on the part of Standard Gravure based on 13 that rule and in large part based on even Mr. Carroll's 14 cross-examination of that expert. 15 JUDGE POTTER: I'll try to read his deposition 16 and I will see you-all at 7:30, and I don't know what to do 17 about Mr. Croft. 18 MS. ZETTLER: I think we should at least get 19 some sort of narrative or some sort of diagnosis, Judge. 20 JUDGE POTTER: I'm going to have my secretary 21 call Doctor Comer. 22 (PROCEEDINGS TERMINATED THIS DATE AT 5:05 P.M.) 23 * * * 24 25 225 1 STATE OF KENTUCKY )( )( Sct. 2 COUNTY OF JEFFERSON )( 3 I, JULIA K. McBRIDE, Notary Public, State of 4 Kentucky at Large, hereby certify that the foregoing 5 Transcript of the Proceedings was taken at the time and place 6 stated in the caption; that the appearances were as set forth 7 in the caption; that prior to giving testimony the witnesses 8 were first duly sworn; that said testimony was taken down by 9 me in stenographic notes and thereafter reduced under my 10 supervision to the foregoing typewritten pages and that said 11 typewritten transcript is a true, accurate and complete record 12 of my stenographic notes so taken. 13 I further certify that I am not related by blood 14 or marriage to any of the parties hereto and that I have no 15 interest in the outcome of captioned case. 16 My commission as Notary Public expires 17 December 21, 1996. 18 Given under my hand this the__________day of 19 ______________________, 1994, at Louisville, Kentucky. 20 21 22 23 24 _____________________________ 25 NOTARY PUBLIC