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 TUESDAY, OCTOBER 25, 1994 15 VOLUME XXII 16 17 * * * 18 19 20 21 _____________________________________________________________ REPORTER: JULIA K. McBRIDE 22 Coulter, Shay, McBride & Rice 1221 Starks Building 23 455 South Fourth Avenue Louisville, Kentucky 40202 24 (502) 582-1627 FAX: (502) 587-6299 25 2 1 2 I_N_D_E_X _ _ _ _ _ 3 4 Hearing in Chambers...................................... 4 5 WITNESS: DOCTOR_NANCY_LORD _______ ______ _____ ____ 6 Further Examination by Ms. Zettler....................... Further Examination by Mr. Freeman....................... 7 Further Examination by Ms. Zettler....................... 8 WITNESS:__DOCTOR_ALAN_BROWN ________ ______ ____ _____ 9 Examination by Mr. Smith................................. Examination by Mr. Myers................................. 10 Further Examination by Mr. Smith......................... 11 WITNESS:__DOCTOR_JOHN_H._HEILIGENSTEIN (By Written Deposition) ________ ______ ____ __ _____________ 12 Examination by Mr. Smith................................. 13 * * * 14 Hearing in Chambers...................................... 15 Reporter's Certificate...................................209 16 * * * 17 18 19 20 21 22 23 24 25 3 1 2 A_P_P_E_A_R_A_N_C_E_S _ _ _ _ _ _ _ _ _ _ _ 3 4 FOR THE PLAINTIFFS: 5 PAUL L. SMITH Suite 745 6 Campbell Center II 8150 North Central Expressway 7 Dallas, Texas 75206 8 NANCY ZETTLER 1405 West Norwell Lane 9 Schaumburg, Illinois 60193 10 FOR THE DEFENDANT: 11 EDWARD H. STOPHER 12 Boehl, Stopher & Graves 2300 Providian Center 13 Louisville, Kentucky 40202 14 JOE C. FREEMAN, JR. LAWRENCE J. MYERS 15 Freeman & Hawkins 4000 One Peachtree Center 16 303 Peachtree Street, N.E. Atlanta, Georgia 30308 17 18 * * * 19 20 21 22 23 24 25 4 1 The Transcript of the Proceedings, taken before 2 The Honorable John Potter in the Multipurpose Courtroom, Old 3 Jail Office Building, Louisville, Kentucky, commencing on 4 Tuesday, October 25, 1994, at approximately 8:35 A.M., said 5 proceedings occurred as follows: 6 7 * * * 8 9 (HEARING IN CHAMBERS) 10 JUDGE POTTER: I don't think we need to be in a 11 race as to who is going to answer the jury's questions. If 12 one of you has it, and they suggested Plaintiffs' No. 200. 13 MS. ZETTLER: We're having that copied right 14 now. 15 MR. FREEMAN: I've got the original and the 16 corrected copy, and I want to introduce both of them and an 17 explanation of what the situation is. 18 JUDGE POTTER: See, I don't know if Ms. Lord is 19 the witness to do it because she doesn't know -- I mean, 20 somebody can ask her, "Ms. Lord, what do you think corrected 21 copy means," and she can say, "I've been told," and then 22 you-all can agree on what she's going to say. Do you see what 23 I mean? I mean, I'm sure she's not the proper witness to do 24 this. Does she know what this corrected copy stamp means? 25 MS. ZETTLER: Yes, she does. 5 1 JUDGE POTTER: If she knows, all right. 2 MS. ZETTLER: She does. 3 JUDGE POTTER: And then if there's -- are you 4 having No. 200 done up? 5 MS. ZETTLER: It's being copied right now. 6 MR. FREEMAN: We're both doing it then. 7 JUDGE POTTER: When will it be here? 8 MS. ZETTLER: Probably by nine, by the time we 9 get started. 10 JUDGE POTTER: I don't want to get into any 11 gamesmanship about who asks the questions to the jury. 12 MR. FREEMAN: Well, it's my document in terms of 13 being a Lilly document. 14 MS. ZETTLER: But on the other hand, Judge, 15 they've answered plenty of questions during their questioning, 16 too, and we haven't raised an objection as to who gets to 17 answer what questions. 18 JUDGE POTTER: So I'm going to do it at 9:00. 19 MS. ZETTLER: As long as it's consistent 20 throughout the rest of the trial, because they've had 21 opportunities to educate the jury in their questioning that we 22 have not had. I mean, I just don't want it to look like 23 they're giving them all the information they're asking for and 24 we're refusing to answer their questions. 25 JUDGE POTTER: Each of you can educate the jury 6 1 in your own way. What we're down to here is a juror's 2 question, and I think each side wants to appear responsive to 3 it. 4 MR. FREEMAN: Well, the fact of the matter is 5 that it's in the depositions already. And the fact of the 6 matter is when it comes in the CRA checks it to see if any of 7 it is incomplete or not correct in terms of what it appears. 8 They will call the site and check to make sure it's correct. 9 They ask, for example, if they didn't write down the weight, 10 "Did you get the weight? Yes, I did," and then they send a 11 complete corrected copy to the site for FDA audit purposes and 12 they keep a complete uncorrected copy, and I have both. 13 MS. ZETTLER: And the other side of that, Judge, 14 is one of the things we did not get into on direct is that 15 many times a corrected copy is stamped corrected and they are 16 not asking the investigators or anybody else who made the 17 changes to initial them. 18 JUDGE POTTER: We're down to a simple thing. 19 Normally when these questions come in I show them to you, and 20 whoever picks them up the next time can go ahead to ask the 21 question to satisfy the jury. It just so happens that as to 22 Exhibit No. 200, it took some time to prepare it and you're 23 both wanting to introduce it this morning. I'm going to tell 24 the jury for their example here's 200, so you'll see what a 25 complete one looks like. As to what a corrected copy means, 7 1 you can both thrash that one out, if this is the proper 2 witness to do it. 3 Let's turn to one other thing. Mr. King will be 4 here shortly. Let's turn to one other thing. And I've 5 thought about this, and normally when I have a problem what I 6 do is get both sides to tell me what they want and then try 7 and navigate through it rather than -- navigate through their 8 suggestions, rather than try and make some suggestions. And, 9 quite frankly, you-all will have to tell me what I ruled 10 because I know we had some hearings and I ruled on certain 11 things regarding production of documents, but I do think that 12 Plaintiffs are entitled to get in that they have not had -- 13 they have requested and Lilly has not provided to them full 14 access to all documents because, presumably, part of the 15 equation the jury might use is if they had gone through 200 16 reports how come they only have 10 out here. My memory would 17 be you-all have the complete pivotal trials; is that right, 18 the case reports and everything on the pivotal trials? 19 MS. ZETTLER: That was produced; right. 20 JUDGE POTTER: Then we had a hearing and I let 21 you pick 300 files. 22 MS. ZETTLER: Three hundred patients' worth of 23 studies. 24 JUDGE POTTER: Six reports of studies or 25 something like that? 8 1 MR. MYERS: It adds up to about 2,000 patients. 2 MS. ZETTLER: That's not true. 3 JUDGE POTTER: Well, whatever it was. What did 4 you-all pick? She said something about just picking a box. 5 MS. ZETTLER: No. No. What happened was is 6 there are -- you said we could pick as many patients on the 7 nonpivotal trials as were on the pivotal trials that will we 8 picked, and it averaged out to about 500 or something like 9 that. And we went through and we tried to -- we picked it 10 basically by numbers, okay. It ended up being about 15 11 studies total. Some of them are 2-patient studies; some of 12 them are 150-patient studies but -- including the pivotals. 13 But the fact is is that we were limited to those very few 14 studies out of a couple of hundred, two or three hundred. 15 MR. FREEMAN: I think it's unfair to get into 16 hearings that we've had on discovery matters when they made a 17 motion for protective order on that very issue that you 18 granted, and this is very prejudicial to us. 19 JUDGE POTTER: What motion did they make, sir? 20 MR. FREEMAN: They made a motion that neither 21 party would be permitted to discuss with the jury the lack of 22 production of any documents or the lack of responsiveness to 23 any discovery, and the Court granted it. 24 JUDGE POTTER: Let me read what I did do. Okay. 25 So it worked out to -- why did I -- what did you-all interpret 9 1 the number 300 subjects to be? 2 MR. MYERS: Up to 300 patients in as many trials 3 as they wanted to pick. And in fact, Judge, they picked 4 nonpivotal studies 1 through 17, 54 and 55, for a total of 241 5 patients, some 31,000 pages, and in the MDL 4 studies, for a 6 total of 1393 patients. So it's about 1600 and some-odd 7 patients. 8 JUDGE POTTER: So the 1300 MDL is the pivotal 9 studies? 10 MS. ZETTLER: Right. That was already produced 11 prior to this litigation. 12 JUDGE POTTER: All right. I understand what 13 we're talking about now. But I think so we don't get into 14 fights or orders or anything, I think the answer is that Lilly 15 produced everything that they were required to produce under 16 the Rules of Civil Procedure, because I am sensitive about my 17 ordering or not ordering or anything like that. My orders 18 simply carry out the Rules of Civil Procedure, and it seems 19 like to me that is a fair way to present it to the jury, that 20 Ms. Lord -- I don't know who wants to get it in or how it gets 21 in, but it seems like to me that if you want to, you're 22 entitled to get in that you have had limited access to their 23 documents; that the reason you've had limited access is you've 24 asked them for everything and they have produced only what 25 they are required to produce by the Rules of Civil Procedure, 10 1 and I think the Rules of Civil Procedure gives it an 2 impartial -- you're not fighting over it; it's a rule. 3 MR. MYERS: Judge, just a point of clarity, the 4 numbers that I gave you pivotal and nonpivotal, those are 5 simply what were remasked pursuant to the MDL's orders and 6 your order. There have been far more made available in 7 unredacted form. And your order and the MDL order included it 8 to come back for a good-cause showing and there was no 9 application made in either court, and I think that that needs 10 to be made clear for the record and it's in the order. 11 MS. ZETTLER: Bull. 12 JUDGE POTTER: What I think the jury is entitled 13 to know is that they have not had complete unrestricted access 14 to -- 15 MS. ZETTLER: The over 200 studies that Joe was 16 trying to allude to yesterday. 17 JUDGE POTTER: Right. But I think also they 18 have to know that Lilly has produced everything that you're 19 entitled to under the Rules of Civil Procedure. 20 MS. ZETTLER: So I will ask her this, I will 21 say, "Under the Rules of Civil Procedure here in Kentucky are 22 you aware of the total number of studies that we have been 23 allowed to look at?" And we'll add it up and we'll say 20, 24 because that's what Larry was rattling off, and she'll say, 25 "We were allowed to see 20 studies, period." The point is is 11 1 we have fought over this issue time and time again. I've 2 spent two years of my life fighting with you, Larry. The 3 problem is that we have fought over this issue and the NDA in 4 state courts ALL over this country. The best we have been 5 able to do is get them to uncover the patient numbers and the 6 investigator numbers on these 20 studies, period. Without 7 these numbers, these studies are worthless to us. We cannot 8 track what's been happening. 9 MR. MYERS: We'll move to renew the application 10 in your order and in the MDL order. 11 MS. ZETTLER: We did that with you, Judge, and 12 we were unsuccessful. 13 JUDGE POTTER: The point is, I don't -- on the 14 Rules of Civil Procedure at the trial level, my orders are the 15 rules. It's kind of like the Supreme Court says what the 16 Constitution means. So, you know, people say the Constitution 17 requires this; other people say the Supreme Court requires 18 this, and I think it's more objective to say under the Rules 19 of Discovery, under the Rules of Civil Procedure they were 20 only required to produce certain documents and they've 21 produced everything that they were required to produce, but 22 nothing more. And then if you want to explain what you've had 23 access to, I think you're entitled to do that. 24 MR. STOPHER: Could I make a suggestion that you 25 say that to the jury -- 12 1 MR. FREEMAN: I think absolutely. 2 MR. STOPHER: -- rather than bringing it out 3 through a witness, because it's your order and you will do it 4 in an even-handed manner. 5 JUDGE POTTER: But what this involves is coming 6 to an agreement on what they have seen. 7 MR. STOPHER: I understand. I don't think 8 there's any dispute about that. But my point is I think if we 9 get down to instructing what the Court's ordered and what the 10 Rules of Civil Procedure, I think that's something for the 11 Court to instruct the jury about rather than for witnesses and 12 lawyers to be arguing about. 13 MS. ZETTLER: I have no problems with that, 14 Judge, as long as you make it clear that the reason that this 15 is being explained is that because Mr. Freeman alluded to 200 16 studies that we had access to and we did not. 17 MR. FREEMAN: They have had access to 200 18 studies. And you could have come back if you had seen 19 anything in any of these documents and moved to get any one of 20 them and you didn't. 21 JUDGE POTTER: Wait. Wait. Wait. Can we -- 22 there are pivotals and those are two studies? 23 MR. FREEMAN: No, sir. 24 MS. ZETTLER: Four. 25 MR. MYERS: There are four remasked pivotal 13 1 studies. 2 MS. ZETTLER: You were supposed to remask all 3 the pivotals. 4 JUDGE POTTER: How many pivotal studies went to 5 the FDA in the first place? 6 MR. MYERS: The FDA makes reference in the 7 summary basis of approval to more than four studies. 8 JUDGE POTTER: But remask means uncovered? 9 MR. FREEMAN: That's right. 10 JUDGE POTTER: So there were four pivotal with 11 the patient numbers -- 12 MR. MYERS: And the investigator numbers 13 unredacted. 14 JUDGE POTTER: And there were how many 15 nonpivotal? 16 MS. ZETTLER: Seventeen or nineteen. 17 MR. MYERS: Nineteen. Thirteen hundred and 18 ninety-three patients in the pivotal, and two hundred and 19 forty-one in the nonpivotal that were remasked. 20 MR. FREEMAN: She says there were 1500 in the 21 pivotal. 22 MR. MYERS: I'm just trying to be precise. 23 MS. ZETTLER: He opens the door for all of this, 24 we didn't bring this out on redirect. And now you're going to 25 rattle off or somebody's going to rattle off these huge 14 1 numbers. The point is is that these were reviewed. He's 2 talking about 200 studies and all this other stuff. Okay. 3 What's prejudicial here is that they have not allowed us to 4 make a reasonable review of these things. They are the ones 5 who originally maxed themes, improperly, and now they're 6 saying we're getting prejudiced by their alluding to us not 7 having reviewed 200 studies that were allegedly available to 8 us when they were not available to us in any kind of form that 9 we could review. 10 JUDGE POTTER: That's the point we're dealing 11 with. I think -- 12 MS. ZETTLER: I would rather have you say that 13 there were a limited number of studies that the patients had 14 available to them to review as opposed to going into numbers 15 of patients, et cetera, et cetera. 16 MR. FREEMAN: That's why the grant of the 17 protective order was made. They've had the 200 studies, they 18 could have come back for further relief and now they're going 19 to take it into court. 20 JUDGE POTTER: We're getting into games about 21 who was pushing and shoving on the rules. 22 MS. ZETTLER: We would prefer, Judge, if you're 23 going to say something and explain how this happened that you 24 don't talk about total numbers of patients, that you talk 25 about numbers of studies. 15 1 MR. SMITH: Well, could we even make it more -- 2 JUDGE POTTER: Are we agreed on the number of 4 3 and 19? 4 MS. ZETTLER: Yes. 5 JUDGE POTTER: Now, the summaries were produced 6 for other studies; is that right? 7 MS. ZETTLER: But they were masked. 8 MR. FREEMAN: You're talking about two different 9 things, summaries and then masked case-report forms. But all 10 the case-report forms were produced. They can go and count 11 how many times agitation appears, for example. 12 MS. ZETTLER: But we can't go and look at the 13 summary and/or the 1639 and match up the patients to see if 14 they correctly reported. Like the woman who was screaming in 15 a fetal position on the floor, they called that confusion. We 16 can't do that without the patient numbers. 17 JUDGE POTTER: All right. We're going to get 18 over the hurdle this way. What I'm going to tell them is, and 19 let you-all in, you need to explain what was produced and what 20 wasn't produced, but to get over why what was produced was 21 produced, I will say that the Plaintiff on the case-report 22 forms, which you-all have seen, and we'll give them No. 200 to 23 start with, someone asked for an example, that the Plaintiffs 24 asked for access to all case-report forms; they were given 25 access to all case-report forms but with all patient 16 1 identification numbers marked out. Under the Rules of Civil 2 Procedure, Lilly was not required to produce all the 3 information, and under the Rules of Civil Procedure they 4 produced 4 pivotal studies and 19 nonpivotal studies in the 5 form you've seen here with the patient numbers on them. And 6 just then you-all can examine your witnesses about what the 7 absence of the numbers means and develop it yourself, but that 8 gets us past why things weren't produced. 9 MS. ZETTLER: All right. Mr. Freeman alluded to 10 a couple of questions he wanted to ask Doctor Lord this 11 morning. I'd like to know what those questions are since he's 12 reopening his cross. 13 MR. FREEMAN: I understand the Court to say that 14 the Court is going to ask these two questions? 15 JUDGE POTTER: No. I'm going to give them 16 No. 200 and then explain why you've got 4 studies and 19 17 studies and then leave it up to you-all if you want to -- I 18 mean, your person can answer corrected copy. What were the 19 questions you had, Mr. Freeman? 20 MR. FREEMAN: I wanted to ask you to 21 respectfully reconsider your ruling on the street drug 22 business. I think it's really unreasonable to allow a woman 23 to come in here and testify that perhaps from her testimony 24 one could conclude that Prozac should never have been approved 25 and should not be a prescription drug when she is getting on 17 1 the podium and writing a medical article about the fact that 2 she wants crack, marijuana, cocaine, and she wants all of 3 these things legalized so that anybody on the street can buy 4 them. I think that goes directly to her credibility as an 5 expert witness and that I should be allowed to ask her that 6 question because it -- she looks like that she is some Madonna 7 sitting up there when all of a sudden she's come out with 8 these outrageous positions on the very issues that we're 9 dealing here with, and that is whether or not these other 10 drugs, like amphetamines, should be legalized so that people 11 should just go out and buy them and do whatever they dang well 12 pleased, when we know that those drugs without any doubt make 13 people hostile, violent, belligerent and everything else. 14 JUDGE POTTER: I made my ruling rather quickly 15 yesterday, but after I had time sitting up there I became more 16 and more convinced that I did the right thing. So I'm not 17 inclined to change my ruling. As a generational thing, 18 Madonna means one thing to you and something entirely 19 different to Ms. Zettler. 20 MS. ZETTLER: You're so kind. She's not even my 21 generation. 22 JUDGE POTTER: What were your questions, if you 23 had anything else? 24 MR. FREEMAN: If you're going to cover these -- 25 JUDGE POTTER: I'll cover 200. She can cover 18 1 corrected copy. Corrected copy is not an issue; it's the 200. 2 MR. FREEMAN: And then if she covers things that 3 need clarification, I think I have a right to recross. 4 JUDGE POTTER: Okay. Let me go over this one 5 more time. 6 MR. FREEMAN: I think you need to say that it 7 represents 1500 patients or exactly the number because 8 otherwise it is not a factual statement. 9 JUDGE POTTER: Let me write out one. 10 MR. FREEMAN: Judge, if I might just say this 11 one thing further. The federal regulations on this subject 12 require Lilly to redact identifying information, and we can 13 point to the regulation if I need to. I think -- will you 14 please let me complete my statement? 15 MS. ZETTLER: I thought you were finished. I 16 apologize. I apologize, Joe. I thought you were done. 17 JUDGE POTTER: Go ahead, Mr. Freeman. 18 MR. FREEMAN: I think we're getting into a 19 situation where we have sent a commissioner up to determine 20 whether or not Lilly has made a good-faith effort to comply 21 with the orders of this Court, and the commissioner has found 22 that Lilly has complied in a good-faith way with the orders of 23 this Court with the rules as they apply to this. Now, to make 24 it look like that we have secreted something for some untoward 25 reason is not fair and it is not right and it is terribly 19 1 prejudicial, and I think it's going to be grounds for a 2 mistrial. Because we have made the 200 studies available to 3 them; they just didn't happen to like how they were made 4 available and the Court then passed on it. And I think if the 5 Court passed on it, it resolves the issues as to what is fair 6 under the rules and the parties. 7 JUDGE POTTER: What I'm going to do is say both 8 parties, if asked, have asked that I give you an example of a 9 complete case report file. They've agreed this this is 10 Plaintiffs' Exhibit No. 200, and it's the complete file and it 11 will get passed out. 12 MS. ZETTLER: Is it okay if we call it 200A? 13 JUDGE POTTER: Yeah. The parties have also 14 asked me to explain something to you. The Plaintiffs have 15 produced at trial, copies of certain case-report forms. As 16 you've noticed, the names but not the -- the names and 17 identities of the patients were blocked out but not the 18 numbers. As you know, in a lawsuit one side often has to 19 produce records and documents it has for the other side. In 20 this case, the Plaintiffs asked for all case-report forms 21 without the patient numbers blocked out. Lilly has produced 22 the documents it was required to produce under the Rules of 23 Civil Procedure in this case. It has produced 4 pivotal 24 trials with the patient identification numbers on the 25 case-report forms and 19 nonpivotal studies without the 20 1 patient identification numbers blocked out. The other 2 case-report forms have been available but all patient 3 identifying information, including patient number, is blocked 4 out. 5 MR. FREEMAN: And that's blocked out because of 6 federal rules; it's not blocked out just because we wanted to 7 do it. 8 JUDGE POTTER: The point is I think the jury is 9 entitled to know what they've had access to and I think that 10 doesn't say you've hidden anything. It says they'd like to 11 have more, but under the rules you haven't produced it. 12 MR. FREEMAN: Would you put the total number in 13 there for me, Judge? 14 JUDGE POTTER: When one of your people wants to 15 come up, if you want to ask them how many patients are in the 16 four pivotal trials, they can see it. You can ask your client 17 how many patients are in it, but that gives you the 18 background. 19 MR. FREEMAN: If we get into it, I'm going to 20 ask Ms. Lord if she knows. 21 JUDGE POTTER: She may not know. 22 MR. STOPHER: Judge, will you read that opening 23 segment again. I thought -- maybe it's my ear maybe there's 24 something in there that's grammatically... 25 JUDGE POTTER: It may read a little bit 21 1 differently because I'm going from notes. The parties have 2 asked me to give you an example of a complete set of 3 case-report forms for a particular patient. This exhibit is 4 200A, which is the one for the patient that was partially 5 shown in Plaintiffs' 200. The parties have also asked me to 6 explain something to you. 7 MR. STOPHER: That's where it is. 8 JUDGE POTTER: No. That's right. The 9 Plaintiffs have introduced at trial copies of certain -- 10 MR. STOPHER: That's the phrase that was 11 confusing to me. 12 MS. ZETTLER: Just so I'm not confused, Judge, 13 can I ask Doctor Lord why we need the patient numbers and 14 investigator numbers in the other studies? 15 JUDGE POTTER: Sure. She can explain why the 16 other 600 are no good to her. She can explainand then he can 17 say, true, but you've had the summaries of the other ones. 18 But this gets -- what I want to get over is people fighting 19 over right or wrong about producing it or my getting involved 20 and putting a stamp of approval on them or criticizing it. 21 We're not through yet. We've still got Mr. King 22 to deal with. Let me ask you this. Would you write down 23 where the other one can't see it whether this one goes or 24 stays, because I'm afraid if one wants him the other one will 25 say no. I may excuse him over anybody's objection, but it 22 1 might just be helpful to know if you-all care. Is Mr. King 2 here? 3 SHERIFF CECIL: No. 4 (RECESS) 5 JUDGE POTTER: Mr. Jeffrey King -- I can't 6 remember his juror number, but he's the welder that sits in 7 the back row on the right-hand side. He is not here this 8 morning. I had my secretary call his home. Apparently his 9 mother had been trying to reach the jury pool but without 10 success, and it's probably because it's Tuesday and they're 11 going through their orientation for new jurors and nobody was 12 there to answer the telephone. 13 Marsha, will you restate for me as accurate as 14 you can what his mother told you? 15 SHERIFF CECIL: She said that Jeffrey went to 16 his family physician yesterday afternoon, J-Town Family 17 Practice. The physician gave him an antibiotic. He had an 18 allergic reaction to this, a severe reaction, she said. He 19 was taken to University of Louisville Hospital at 4:00 this 20 morning. They gave him IVs to flush his system, gave him 21 Donnagel for severe stomach cramps and he was released about 22 7:10 this morning, and she said at this time he's out like a 23 light. 24 JUDGE POTTER: I don't know if you said it, but 25 apparently it's poison ivy. 23 1 SHERIFF CECIL: Yes. He had complained 2 yesterday with poison ivy, a rash, and his hands were going 3 numb, and he had it up his arm and he had gotten into poison 4 ivy over the weekend. 5 JUDGE POTTER: There are two issues here, One, 6 does anybody want to do anything more to confirm the facts 7 about Mr. King's situation? We've got his mother here or we 8 can do other things like that. Does anybody want to do 9 anything else about confirming the facts of his situation? 10 MR. SMITH: No. 11 MR. STOPHER: No. I don't think so, Judge. 12 JUDGE POTTER: Does anybody see any reason that 13 he shouldn't be excused as one of the alternates? 14 MR. FREEMAN: I don't. 15 JUDGE POTTER: Mr. Smith? 16 MR. SMITH: No. 17 MR. STOPHER: I would make a couple of requests 18 in this regard. I would hate for there to be any ripple 19 effect on other jurors, which is going to be to everybody's 20 disadvantage. The second thing is I'd hate for the specifics 21 of this to be mentioned to the jury because, obviously, we're 22 talking about a drug reaction and this just happens to be a 23 case in which that's alleged. I don't know that anybody makes 24 a lot out of that, but I would just simply refer to a medical 25 problem that required medical attention and that prevents him 24 1 from participating any further. 2 MR. SMITH: That would be all right with me, 3 Your Honor, as long as I could have his phone number so I 4 could contact him about a potential malpractice case. 5 MR. FREEMAN: Or to see if it was a Lilly drug. 6 MS. ZETTLER: Yeah. 7 JUDGE POTTER: There's one other thing I'm going 8 to do. I'm going to recite that he was in the hospital for 9 several hours last night; I'll say his -- let me put it this 10 way. 11 MR. SMITH: Why don't you say his condition is 12 such that he may not be able to return for several days, so 13 that they won't get the idea they can get a cold and go to a 14 GP and get excused. 15 JUDGE POTTER: I wanted to put that his 16 condition got worse. After seeing his family doctor, he went 17 to a hospital last night, he was given IVs. He has returned 18 home, everything is fine, but he's exhausted and out like a 19 light and would not be able to participate for several days. 20 What I want to do is avoid the ripple effect and also make 21 them, like you say, not feel like if they get tired all 22 they've got to do is run down to their GP; that he did go to a 23 hospital and it was fairly serious, but I won't say that he 24 took a -- 25 MR. SMITH: Right. Mr. Smith is not here this 25 1 morning; he's filing a 1639. He's checking the case-report 2 forms to see if he was in a clinical study. 3 MR. FREEMAN: Or if it was a Lilly antibiotic. 4 MR. SMITH: Right. 5 JUDGE POTTER: Are we going to see the 1639 on 6 Mr. Wesbecker at some point with the patient blocked out? I 7 think we ought to be able to spot it. Is the 200A here yet? 8 MS. ZETTLER: Let me check. I'm virtually 9 certain they are. Could I get two minutes to set up for 10 Doctor Lord? 11 JUDGE POTTER: Okay. 12 MS. ZETTLER: And then I'll double-check that 13 and let you know. 14 (RECESS; THE FOLLOWING PROCEEDINGS OCCURRED 15 IN OPEN COURT) 16 SHERIFF CECIL: The jury is now entering. All 17 rise. The Honorable Judge John Potter is now presiding. 18 Court is now in session. 19 JUDGE POTTER: Please be seated. Good morning, 20 ladies and gentlemen of the jury. Did any of you have any 21 problems with the admonition about people communicating with 22 you about this case? How about Mr. Miller, did you have any 23 problems? 24 JUROR MILLER: No. No, sir. 25 JUDGE POTTER: Let me do a couple of things to 26 1 you. First of all, you may have noticed Mr. King is not here. 2 One reason we were late starting this morning was we were 3 trying to check on his condition. You-all may or may not have 4 known yesterday -- I guess you-all are getting pretty friendly 5 back there -- that he had some poison ivy that was getting on 6 him pretty bad. He went to see his family doctor last night 7 and after seeing his family doctor his condition got worse. 8 He went to a hospital last night and spent quite a bit of time 9 there and got some IVs, but his condition is -- he's okay. 10 The problem is he's home, he's knocked out, and the doctors 11 say he wouldn't be able to do much for a couple of days. 12 So I've talked with the attorneys and we're 13 going to excuse Mr. King and go forward without him. This is 14 why we put alternates in the jury box. I'm sure -- and one 15 reason we took so long in getting started is because we don't 16 excuse a juror until we have a pretty good idea of what their 17 situation is and have a pretty good idea that we can't wait a 18 few hours or work around their problem somehow that -- first 19 of all, exactly what their situation is for sure and that it's 20 something we can't work around, so that's really why it took 21 us quite awhile to get going this morning because we had to 22 talk to his mother and various other people to verify what his 23 situation was. I've given my sheriff a couple of dollars and 24 she'll stick a get-well card in there later on and you-all can 25 sign off on it if you want to. 27 1 One other thing. Both parties have asked that I 2 give you an example of a complete file with all the 3 case-report forms for one patient. They're out there on the 4 table, Marsha, if you would pass them out. You-all had some 5 excerpts from a file yesterday and what they've done, both 6 sides have given you the entire file that went with 7 Plaintiffs' Exhibit No. 200, and that's just done so you'll 8 have a background at which to judge the various pieces that 9 have come in. 10 SHERIFF CECIL: (Hands document to jurors). 11 JUDGE POTTER: Okay. Let me say one other thing 12 to you. The parties have asked that I explain something to 13 you, and I want you to listen up, so if you'll put your new 14 exhibit down and look at it at a different time. That's one 15 of the dangers of passing out a lot of material to you, and 16 various judges have different views about it, is that you get 17 so busy reading your material you don't listen to what's 18 happening up here, so I caution you-all about that. When 19 you're given exhibits use them to go with the witness, but 20 don't get so involved in them that you spend your time reading 21 something different from what's going on on the witness stand. 22 But the parties have asked me to explain 23 something to you. Yesterday -- and you know for the rest of 24 this trial -- the Plaintiffs have introduced at trial copies 25 of certain case-report forms. As you have noticed, the names 28 1 but not the patient numbers were blacked out on the 2 case-report forms that they introduced. As you also may know, 3 before a lawsuit, the various parties take discovery of each 4 other and depositions that you've heard read were part of that 5 process. Also, as you may know, in a lawsuit one side often 6 has to produce records and documents it has for the other 7 side. In this case, the Plaintiffs asked for all case-report 8 forms without the patients' numbers blocked out. Lilly has 9 produced the documents it was required to produce under the 10 Rules of Civil Procedure that govern pretrial discovery. It 11 has produced 4 pivotal trials and 19 nonpivotal studies 12 without the patient numbers blocked out. The other 13 case-report forms have been available to the Plaintiffs, but 14 all patient identifying information, including the patient 15 number, was blacked out. Both parties asked me to give you 16 that background on something that's gone on prior to trial. 17 Doctor Lord, I'll remind you you're still under 18 oath. 19 Ms. Zettler. 20 MS. ZETTLER: Thank you, Your Honor. 21 22 23 24 25 29 1 FURTHER_EXAMINATION _______ ___________ 2 3 BY_MS._ZETTLER: __ ___ _______ 4 Q. Doctor Lord, I've got a few questions to follow 5 up from yesterday, but before we get into that, could you 6 explain to the jury -- we've seen on the exhibits that we went 7 through yesterday some patients stamped with a corrected copy 8 stamp. Could you explain to the jury what that means? 9 A. There were errors in one set and corrections 10 were made in the corrected copy. 11 Q. So the copy that they have -- or at least the 12 pages that are stamped "corrected copy" are the copy where 13 errors were corrected? 14 A. That is correct. 15 JUDGE POTTER: That microphone goes one place, 16 the little brown thing is what broadcasts here in the room. 17 DOCTOR LORD: I'm sorry. I forgot that, sir. 18 I'll keep it straight. 19 JUDGE POTTER: That's all right. You need to do 20 both of them, I guess. 21 Ms. Lloyd -- I mean, Ms. Zettler. 22 Q. Doctor, you've just heard the Judge explain to 23 the jury that there were only a certain number of studies 24 available to us without the patient numbers or the 25 investigator numbers marked out, in other words, the patient 30 1 or investigator numbers weren't available to us. To your 2 knowledge, how many studies were conducted by Lilly on Prozac 3 in depression? 4 A. There were hundreds. 5 Q. And you heard the Judge say that we had 6 available to us 23 studies with the patient numbers and the 7 investigator numbers; correct? 8 A. That's right. 9 Q. You also heard the Judge say that we had 10 available to us the other studies with the patient numbers and 11 investigator numbers blacked out; correct? 12 A. That's right. 13 Q. Would those studies with patient numbers and 14 investigator numbers being blacked out have been of any value 15 in your evaluation of whether or not Lilly did something 16 adequately or inadequately? 17 A. It would have been of very, very little value 18 because the problem is that you could not track what was 19 happening with one case report to what was done with that 20 information in either the study summary or the 1639s. Without 21 the investigator -- without at least identifying initials for 22 the investigator, you couldn't possibly tell. Without some 23 sort of patient number you couldn't find which 1639 belonged 24 to that particular patient, so there would be no way to tell 25 what happened to that particular person. 31 1 Q. So, in other words, we couldn't do what we did 2 here, follow the patient's progress through the clinical 3 trial, how it was reported on a 1639 and how it was reported 4 in a case summary; correct? 5 A. That's correct. Couldn't do that. 6 Q. All right. And, Doctor Lord, you had 7 approximately -- I think it was around 2,000 patient 8 case-report forms to look at; correct? 9 A. That's right. 10 Q. And those included, as the Judge said, 11 case-report forms from pivotal as well as nonpivotal trials; 12 correct? 13 A. That's right. 14 Q. And how many of those individual patient 15 case-report forms did you in fact review? 16 A. I reviewed several complete studies, and it was 17 somewhere between 100 and 200 actual forms. I also 18 spot-checked the other ones, you know, I went through the 19 other boxes and pulled a couple of forms at random and went 20 through those. 21 Q. Why didn't you review every single patient of 22 these approximately 2,000 patients? 23 A. Well, it took me a week to review the ones that 24 I did, and at the time that that was over, I was satisfied 25 that I had observed a pattern. The ones that I showed you 32 1 yesterday were simply examples of a pattern that I saw in 2 virtually all of the forms that I reviewed. I mean, not that 3 every form had a problem, but it was happening often enough 4 that I saw a pattern there. 5 There were other similar problems. For 6 instance, I recall one patient on Protocol 27, a pivotal 7 study, that took Artane, Navane and Pamelor; two of these are 8 antipsychotic meds, for drinking too much caffeine. 9 MR. FREEMAN: I object to her testifying unless 10 she can particularly identify the patient she's talking about 11 so that we may follow what she's talking about, Judge. 12 JUDGE POTTER: I'm going to overrule the 13 objection, but I think for clarity and to save us time later, 14 to the extent possible your client ought to identify any 15 source she talks about. 16 MS. ZETTLER: I understand, but I couldn't hear 17 Joe's objection at first. Okay. 18 MR. SMITH: Objection is overruled. 19 MS. ZETTLER: I know. 20 A. I can identify it. Protocol 27. It was one of 21 Doctor Fabre's patients. 22 Q. Do you remember specifically the patient number 23 for that study? 24 A. I could find it; it's written down somewhere. 25 Q. Did you find examples of errors in other 33 1 studies, in general? 2 A. Yes, I did. 3 Q. Okay. You said earlier that it took you 4 approximately a week to look at the case-report forms that you 5 had looked at; correct? 6 A. That's right. 7 Q. And, Doctor, you looked at those case-report 8 forms to determine whether or not errors were made in the 9 reporting of the data, did you not? 10 A. That's right. 11 Q. That was your specific objective, to look at 12 those case-report forms to determine whether or not things 13 were reported correctly, et cetera; correct? 14 A. That is right. I looked at the case-report 15 forms with the knowledge that I had from having the same job 16 at Abbott as a monitor, to make sure that these case-report 17 forms were completed and the data reported correctly. 18 MS. ZETTLER: May I approach, Judge? 19 JUDGE POTTER: Uh-huh. 20 Q. Yesterday Mr. Freeman stacked next to each other 21 these two groups of documents. Now, my understanding is one 22 of the case-report forms is now missing so it may be a little 23 thicker than this but... Mr. Freeman asked you if there was 24 information in the case-report forms such as the numbers of, 25 you know, times that adverse events were reported within the 34 1 case-report forms. I believe he was trying to make the point 2 that it was reported numerous times within there at various 3 places, at least in the one case that he showed you. Okay? 4 Is that actually part of the problem, the amount of documents 5 that you have to go through to find that information? 6 A. Well, yes. Exactly. These case-report forms 7 here were part of a large box, and I had to go through all of 8 that to get, in addition to this, the other ones that I found. 9 But this is what I had to get through to find these pages as 10 examples. 11 That's exactly the problem that I was trying to 12 explain yesterday. Just putting it in the case-report form is 13 not good enough because somebody may not see it. You must put 14 the information in the place that the Food and Drug 15 Administration is most likely to see it, and that would be the 16 adverse experience reports and the -- or the study summary, 17 and it must be in both. 18 Q. The adverse event reports you're talking about 19 are the 1639s we talked about yesterday; correct? 20 A. That's right. 21 Q. And are those, in your experience, filed with 22 the case-report forms themselves? 23 A. No. Those are filed separately. As I said 24 yesterday, most of them are filed at the end of the study. 25 Q. Okay. And, again, who in your experience fills 35 1 out the 1639s? 2 A. Our division did, the Abbott Laboratories filled 3 them out based on what was in the case-report forms or if a 4 doctor called up with some sort of adverse reaction. 5 Q. And if we could use the example of the woman, I 6 think it was Patient 44, who was found in a fetal position 7 screaming and refusing to eat, do you remember that example? 8 A. That's correct. 9 Q. My question is, is it your recollection that 10 they listed confusion on the 1639 for that patient who was 11 thought to be psychotic and in a fetal position screaming? 12 A. That is correct. That's exactly what they did. 13 And there's another problem there. Had they listed that 14 adverse experience as it really was, it would have been a 15 serious and unexpected reaction and should have been reported 16 rather quickly, expeditiously, but as confusion it could have 17 been reported at the end. 18 Q. Okay. And in your experience, would an FDA 19 person reviewing the 1639s be alerted to anything unusual by 20 that 1639 listing confusion? 21 A. Absolutely not. 22 MR. FREEMAN: Your Honor, that's not an 23 appropriate question to ask would the FDA. 24 JUDGE POTTER: Objection is overruled. It's 25 kind of preliminary. 36 1 Q. And does that 1639 for that particular patient 2 in your opinion properly reflect the severity of the woman's 3 condition? 4 A. Of course not. Somebody reading, whether an FDA 5 official or anybody else, the word "confusion" would have no 6 idea the severity, the complexity and the psychosis that this 7 woman experienced. Confusion can be a number of things. 8 People who come into psychotropic drug trials report many 9 things like confusion. It would not be taken seriously. I 10 think that's very obvious. 11 Q. Yesterday Mr. Freeman asked you if at least 12 while you were at Abbott a study on violent-aggressive 13 behavior in the use of your drug was conducted. Do you recall 14 that? 15 A. Yes, I do. 16 Q. Do you recall whether there was one done? 17 A. No, there wasn't. 18 Q. Why not? 19 A. Well, because we didn't have clear signs of a 20 problem in regard to violent-aggressive behavior. We didn't 21 have cats that had been friendly that started to hiss and 22 growl; we didn't have dogs that developed ataxia and then bit 23 their handlers; we didn't have patients on preliminary 24 open-label studies that flipped out and remained in fetal 25 positions screaming for three days, and eloped from the 37 1 hospital and had to be brought back in custody. We didn't 2 have those problems. There was no reason for us to perform a 3 special study on hostile and aggressive behavior. That was 4 not the problem with my drug. 5 Q. Did a foreign regulatory agency ever contact 6 Abbott and say, "We have concerns about your drug, that it may 7 be stimulating and it may cause increased risk of suicidal and 8 violent behavior"? 9 A. No. 10 Q. Was your drug a sedative? 11 A. Yes, it was a sedative hypnotic. 12 Q. Did it have any stimulant properties, as far as 13 you know? 14 A. Not that I know of, no. 15 Q. No further questions, Your Honor. 16 JUDGE POTTER: Mr. Freeman. 17 MS. ZETTLER: I'm sorry. I take that back. I 18 have one other question, if that's okay. 19 JUDGE POTTER: Okay. 20 Q. I'm sorry, Doctor. I'm going to -- may I 21 approach, Judge? 22 JUDGE POTTER: Uh-huh. 23 Q. I'm going to show you the document that Mr. 24 Freeman showed you yesterday. 25 A. Yes. 38 1 Q. Do you recall that document? 2 A. Yes, I do. 3 Q. Can you tell the jury what that document is? 4 A. This is the Review and Evaluation of Efficacy 5 Data that was prepared by the Food and Drug Administration. 6 Q. And Mr. Freeman had you read over one portion, I 7 think it was one paragraph within that entire document, 8 related to concomitant medications? 9 A. That's right. 10 Q. Have you had a chance to look at more in that 11 document, Doctor? 12 A. Yes, I have. 13 Q. Could you tell the jury, to put it in proper 14 perspective, what that paragraph referring to concomitant 15 medications was talking about? 16 A. Well, taken in context this paragraph is 17 addressing the issues of efficacy and whether the use of 18 concomitant medications might have somehow affected the data 19 in regards to efficacy. They were not looking at it here from 20 a safety perspective. It was also stated right in the 21 paragraph that when they added all these medications up, they 22 also included a number of compounds which, quote, in addition, 23 however, there were other drugs administered which do not have 24 a psychotropic effect, but which do have a CNS effect and 25 which interact with psychotropic agents which were not 39 1 originally identified by the sponsor. Such compounds include 2 Propanolol, that's a high blood pressure medication; 3 Clometadine, that's an ulcer drug, I believe; Fiorinal, pain 4 killer; meperidine is a pain killer; diphenhydramine is an 5 antihistamine; phenylpropanolamine is a cold medicine; 6 phenylpropanolamine and caffeine. So they were jumbling all 7 of these drugs up with the sedatives, and no one has really 8 looked at how many of the fluoxetine patients got sedatives 9 compared to the imipramine patients. 10 And the other thing that wasn't done is nobody's 11 compared how many fluoxetine patients taking different dose. 12 This was a titrating dose study that the investigator could 13 use varying amounts of dosages in different patients, and they 14 didn't look at how many of the people on a higher dose as 15 opposed to a lower dose required sedatives. So this really 16 doesn't provide any real, you know, data in terms of the 17 effect of those concomitants on the issues of safety. 18 Q. Okay. Just so it's clear, though, this is a 19 review of efficacy and not safety; correct? 20 A. That's right. 21 Q. And that area that Mr. Freeman showed you 22 yesterday, including that paragraph, is not doing an analysis 23 of the number of adverse events that people were experiencing 24 that required these drugs; correct? 25 A. This whole section here addresses the efficacy 40 1 issues. 2 Q. When you say -- just a point of clarification. 3 When you said the other drugs had CNS effects, you meant 4 central nervous system; correct? 5 A. Right. Exactly. 6 Q. All right. That's all I have, Your Honor. 7 JUDGE POTTER: Mr. Freeman. 8 9 FURTHER_EXAMINATION _______ ___________ 10 11 BY_MR._FREEMAN: __ ___ ________ 12 Q. Yesterday I asked you, Doctor Lord, several 13 questions about your NDA that you had worked on while you were 14 at Abbott; do you remember that? 15 A. That's right. Yes. 16 Q. And what was the trade name for the drug that 17 was later marketed? 18 A. The trade -- we didn't have a trade name when I 19 was there; I believe the trade name now is Prosom. 20 Q. Prosom? 21 A. Uh-huh. 22 Q. And is it -- what class of drug is it? 23 A. It's a benzodiazepine hypnotic; it's a sleeping 24 pill. 25 Q. What is Restoril? 41 1 A. Restoril is another benzodiazepine hypnotic. In 2 fact, they were going through drug development at the same 3 time. We used a number of the same investigators, et cetera. 4 Restoril, like my drug, estazolam, is a shorter-acting 5 hypnotic that allows people to get up in the morning; it 6 doesn't have the long anxiolytic effect. Say, Dalmane, one of 7 the good things about Dalmane is if somebody has a little 8 anxiety and you give it to them to go to sleep, they'll have a 9 tranquilizing effect the whole next day, as well. But that 10 can be a problem for people that may have trouble getting up 11 in the morning on Dalmane because it's still in their system. 12 So Restoril, along with my drug, estazolam or Prosom, were 13 developed to -- in the hopes of getting something better that 14 would allow people to get up in the morning faster and feel 15 better right away, and it wouldn't have that anxiolytic 16 effect. 17 Q. And both of them are benzodiazepines, I believe 18 you indicated? 19 A. That's correct. 20 Q. And you indicated in your examination just a 21 moment ago that Ms. Zettler asked you about is that your drug 22 was a sedative; is that correct? 23 A. A hypnotic, a sedative hypnotic. 24 Q. But you used the word sedative, did you not, 25 earlier? 42 1 A. That's correct. Yes. 2 Q. And the same thing applies to Restoril. It is a 3 sedative and has a sedative effect, as well, does it not? 4 A. Yes. But as I just explained to the jury, the 5 sedative effect goes away in the morning. It keeps the people 6 asleep, but then they wake up and you don't have that 7 prolonged sedative tranquilizing effect the whole next day. 8 Q. But both of them are the same class drugs and 9 both of them are sedatives, are they not? 10 A. That's right. 11 Q. Now, could we mark this one next, please? While 12 they're marking that, Doctor, what is the Physicians' Desk 13 Reference book? 14 A. That is a book that is published by a company by 15 the name of Medical Economics in Oradell, New Jersey, and it 16 is a compilation of the package inserts of various drugs. 17 MS. ZETTLER: Your Honor, may we be heard? 18 (BENCH DISCUSSION) 19 MS. ZETTLER: Your Honor, Mr. Freeman is going 20 to seek to introduce into evidence a copy of the package 21 insert for Prosom. It's hearsay and immaterial to this 22 whether or not this particular drug has any adverse effects. 23 JUDGE POTTER: Mr. Freeman? 24 MR. FREEMAN: Your Honor, I think I have a right 25 to introduce the package insert that goes with her drug 43 1 because it lists the things that she's complained about about 2 Prozac, and it goes to the whole credibility of when she says 3 contraindications for people that are violent or -- 4 MS. ZETTLER: It doesn't do that. What it says 5 is that the class of drugs themselves may have a paradoxical 6 worsening. There's a huge difference there. 7 MR. FREEMAN: It is the same class drug as 8 Restoril, and one of the issues in this case is whether or not 9 this drug and Restoril are sedatives. Both she and Doctor 10 Breggin have said they are sedatives. 11 MS. ZETTLER: I think admitting this is just 12 prejudicial. 13 JUDGE POTTER: I think we went through these 14 questions yesterday and, as I remember it, the idea is it's 15 the follow-up on she didn't have her drug tested for anything. 16 MR. FREEMAN: I just want to get in the 17 document. 18 JUDGE POTTER: Right. Right. Which is the part 19 that says there are certain people that shouldn't take this 20 thing and yet she did not test for -- I forget, what is it, 21 agitated or whatever the types of things? 22 MS. ZETTLER: The difference is we already have 23 a class of drug that has been on the market. If you look at 24 it, it's a class warning and it's not a warning particular to 25 this drug down here. Okay? Part of the reason they didn't 44 1 test it is because they already knew the drug had a 2 paradoxical worsening. For her to -- for him to claim that 3 this is the only drug in that class that does this, and then 4 try to, you know, put on her a duty to test -- or put on the 5 company a duty to test when they were already going to have 6 this warning in there, that's the point here. 7 JUDGE POTTER: I'm going to overrule the 8 objection. 9 MS. ZETTLER: Am I going to have an opportunity 10 to clarify this? 11 JUDGE POTTER: Yeah. 12 (BENCH DISCUSSION CONCLUDED) 13 Q. If you would please look, ma'am, at Exhibit 14 No. 204. Is that the Physicians' Desk Reference book copy of 15 the package insert on the drug that you have earlier talked 16 about? 17 A. It appears to be that, sir. 18 Q. Now, as will happen with various medications, I 19 believe I have shown you or my co-counsel has shown you 20 Exhibit No. 199, which is a letter to your former company with 21 respect to the drug that we were just discussing. 22 A. Right. The nonapprovable letter. 23 Q. And it is a -- 24 MS. ZETTLER: I'm sorry, Judge. Could I see a 25 copy of that? 45 1 MR. FREEMAN: Certainly. 2 MS. ZETTLER: Thank you. 3 Q. It is a nonapprovable letter -- 4 MS. ZETTLER: Your Honor, could we be heard on 5 this? 6 (BENCH DISCUSSION) 7 MS. ZETTLER: First of all, this is going way, 8 way beyond redirect. Second of all, this is again hearsay. 9 This is the nonapprovable letter for their drug. She wasn't 10 even there at the time. She was gone in 1984. 11 JUDGE POTTER: Mr. Freeman, what's the relevance 12 of this? 13 MR. FREEMAN: Your Honor, if you will notice the 14 Witness has earlier testified that she left there in December 15 of 1983. This is a letter based on the study that she does 16 and is introduced for the purposes of showing that federal 17 agencies such as the FDA raise questions about medications and 18 later, after they get additional information, go ahead and 19 approve it. This is to show a course of activity that there 20 is nothing unusual about the Germans raising questions; 21 there's nothing unusual about any of these people raising 22 questions because it happened with her own drug. And I have a 23 right to show that because she's trying to make it out, and 24 they have, that it's something highly irregular that anybody 25 ask any questions about this drug Prozac. They asked it about 46 1 hers, as well. 2 MS. ZETTLER: He had his opportunity to do this 3 yesterday, first of all, and he did not. And he also asked 4 more questions he was going to ask this morning to reopen his 5 cross and I did not talk about this. We could have dealt with 6 this earlier. Second of all, I mean, this is a letter that's 7 dated 1987. We don't know what happened in between this time 8 and the time she left. 9 JUDGE POTTER: Mr. Freeman, how much more have 10 you got? 11 MR. FREEMAN: Just three minutes. 12 JUDGE POTTER: I think this is relevant. The 13 very crux of this lady's qualifications is that she nursed an 14 NDA through the process, or at least prepared an NDA and 15 everything that went into the NDA. She's criticizing them for 16 not putting certain things in their NDA, and I do think that 17 this sort of sequelae of what she put in can be relevant 18 provided we don't get bogged down in it. I'm going to have to 19 overrule that objection. We may be back to the same thing we 20 are with the 38 percent. He may show it to her and she says 21 I've never seen it, in which case he gets to take it back. 22 MS. ZETTLER: He can ask her questions, but I 23 strenuously object to that being admitted into evidence. 24 JUDGE POTTER: Well, he's got to lay the 25 foundation. 47 1 (BENCH DISCUSSION CONCLUDED) 2 Q. Earlier, Doctor, when I asked you the question 3 about what Exhibit 199 was, you indicated to the Court and 4 jury that it was a nonapprovable letter? 5 A. That's right. 6 Q. And it is with respect to the study that you had 7 compiled of the NDA? 8 MS. ZETTLER: Your Honor, I object. He still 9 hasn't asked her if she's ever seen the letter before. 10 JUDGE POTTER: Mr. Freeman, I think you need to 11 ask her if she can identify what that is. 12 Q. Can you identify what this is, please, ma'am? 13 A. It appears to be the letter that I never saw 14 until my deposition with your co-counsel, and I have not had a 15 chance to read it completely. It just was kind of shown to 16 me. 17 Q. It was shown to you in your deposition? 18 A. Right. It does say that the application is not 19 approvable. It appears to be what your firm is purporting it 20 to be; however, I have not had a chance to read it in its 21 entirety. 22 Q. Let me ask you a couple of questions about it 23 then, please, ma'am. You left there in December of -- 24 MS. ZETTLER: Your Honor -- 25 JUDGE POTTER: Approach the bench. 48 1 (BENCH DISCUSSION) 2 MS. ZETTLER: They show her this document in her 3 deposition and she says, "If that's what you say it is; I have 4 no way of knowing it." They bring it back out here during 5 trial and she says this is the document you showed me in my 6 deposition. They have not established whether they got this 7 through a Freedom of Information Act request. It's not like 8 anything I've ever seen. 9 JUDGE POTTER: I'm going to sustain the 10 objection to introducing the document. I don't think it's a 11 proper foundation to saying I've never seen this before and 12 this is something you didn't get from them. 13 MR. FREEMAN: We gave it to them in her 14 deposition. They knew that we were going to use it in this 15 case. They have shown document after document after document 16 to people that have never seen it and the Court has let those 17 in. 18 JUDGE POTTER: We're back to the 38 percenter. 19 You know, just because it's been in the lawsuit, unless 20 somebody can say, yes, I know what it is, it doesn't come in. 21 So I'm going to sustain the objection and further examination 22 of her about it. 23 MR. FREEMAN: Not even to show a course of 24 conduct? 25 JUDGE POTTER: That's right. 49 1 MS. ZETTLER: Can I just state for the record 2 Abbott's course of conduct is not relevant to this case. 3 (BENCH DISCUSSION CONCLUDED) 4 Q. Now, in your testimony you answered a number of 5 questions about agencies and how they conducted their business 6 in terms of the FDA; is that correct? 7 A. Well, there were a few things I knew about it. 8 I can't say I made extensive -- gave extensive testimony on 9 how they conducted their business. 10 Q. Is there anything unusual about the FDA or the 11 BGA or anyone in that capacity, that is, of the agency asking 12 a pharmaceutical company questions about their medication that 13 they seek to get approval? 14 A. Absolutely not. That's why they're there. 15 Q. And sometimes these questions come to the 16 company in the form of a letter which says, "We intend not to 17 approve your product"? 18 A. That's right. 19 Q. And then later those questions are answered by 20 the drug company, hopefully by either additional studies or 21 additional information or additional data? And that's right, 22 isn't it? 23 A. That's true. 24 Q. And the medication then becomes approved in some 25 instances? 50 1 A. That's right. 2 Q. Now, in going through your background on 3 yesterday, in an effort to determine how much time you spent 4 in this particular area, isn't it so, please, ma'am, that in 5 1992, you ran for Vice-President of the United States? 6 MS. ZETTLER: Objection, Your Honor. 7 JUDGE POTTER: Sustained. 8 MR. FREEMAN: That's all we have at this time, 9 Your Honor. 10 MS. ZETTLER: May I ask a couple of questions, 11 Judge? 12 JUDGE POTTER: Yeah. You're down to the PDR. 13 MS. ZETTLER: Yep. 14 15 FURTHER_EXAMINATION _______ ___________ 16 17 BY_MS._ZETTLER: __ ___ _______ 18 Q. Do you have a copy of the package insert for 19 Prosom in front of you, Doctor? 20 A. Yes, I do. 21 Q. Isn't it true that there's a contraindication 22 listed in here stating that benzodiazepines as a class may 23 cause fetal damage? 24 A. That's right. 25 Q. Isn't it also true that there's a 51 1 contraindication in here that says there's a potential risk to 2 the fetus and that patients are instructed to discontinue the 3 drug prior to becoming pregnant? 4 A. That's right. 5 Q. Isn't there also a warning in this package 6 insert that, like other benzodiazepines, it's a CNS or central 7 nervous system depressant and that patients should be 8 cautioned with regards to engaging in hazardous occupations or 9 duties on the drug? 10 A. That's right. 11 Q. Is there also another indication on here that 12 there were unpredictable effects that have occurred in rare 13 cases on this drug, such as excitement and agitation? 14 A. Right. I believe that occurred mainly with 15 Halcion. 16 Q. Okay. Halcion is another benzodiazepine? 17 A. A very short-acting benzodiazepine. There were 18 some problems in Holland about that. 19 Q. Okay. Now, yesterday when you tried to respond 20 to one of Mr. Freeman's questions, you were trying to explain 21 to him that even though there were no problems with this drug 22 with violent-aggressive behavior, that the drug had problems 23 of its own; correct? 24 A. That's right. 25 Q. Can you give us a couple of examples of what the 52 1 problems are, to begin with? 2 A. Well, on our first initial pharmacokinetic 3 study, the multiple-dose study, two of the patients suffered 4 seizures after the drug was withdrawn. Because of this, a 5 number of people, including an FDA official, had stated they 6 never expected to see this drug approved. The other problem 7 was, as with other benzodiazepines, there is a respiratory 8 suppressive effect. Even back when I was in medical school I 9 was told never, never, never give a benzodiazepine to somebody 10 with respiratory suppression problem because what it does, it 11 suppresses their CO2 reflex and they may not be breathing 12 enough to get oxygen, but they don't wake up in time to start 13 breathing again, and they can die. 14 And there were some deaths in Japan of people 15 who apparently had what's called sleep apnea syndrome, which 16 is a syndrome where people stop breathing when they go to 17 sleep. 18 Q. You said respiratory effects of the drug and 19 seizures? 20 A. Right. 21 Q. Okay. How many seizures do you recall there 22 being on the clinical trials? 23 A. There were just those two; we never had another 24 one. 25 Q. What did your company do in response to those 53 1 two seizures? 2 A. We set up a multiple-dose, double-dose long-term 3 study to evaluate the potential to induce seizures. We gave a 4 number of volunteers -- I don't recall the exact number, maybe 5 around 20, maybe 30, I don't recall -- double doses. The 6 recommend dose was two. The dose we used, we got them up to 7 four milligrams and we took them off cold turkey. We did EEGs 8 before that trial to make sure that the people came in with 9 normal EEGs, and we did EEGs during the withdrawal phase to 10 pick up any tendency to have seizures. And I believe that 11 during that time, the first couple of days the drug was 12 withdrawn we kept them in the hospital, just in case. And by 13 doing that study we were able to assure ourselves -- because I 14 was very concerned about this -- and the FDA that this was 15 just a sporadic reaction in those two volunteers. One of them 16 had been drinking, and the other one was a very tiny guy that 17 should not have been getting that much of the drug. 18 Q. But the point is, in response to these two 19 seizures, your company conducted an entire clinical trial 20 hospitalizing patients, running EEGs and other tests to see if 21 this was a phenomena that was peculiar to your drug, at least 22 in the numbers of events, as opposed to the other drugs in its 23 class; correct? 24 A. That's correct. As we did with the respiratory 25 problem, as well. 54 1 Q. Okay. And you said there were five deaths 2 related in Japan? 3 A. In Japan, I don't recall the exact number. It 4 was a small number, but I don't recall the exact number at 5 this point. 6 Q. And you ran another full-blown study to look 7 into that issue; correct? 8 A. Yes. And I believe yet another one was done 9 after I left, I think there was another one given to me in the 10 documents by the defense firm. 11 Q. You say these problems that you saw really are 12 things that happened with the class of drug known as 13 benzodiazepines; correct? 14 A. Yeah. One more interesting thing I found with 15 the seizures when I did my MedLine on it and looked at what 16 happened with other drugs, there were sporadic reports of 17 seizures with other benzodiazepines, not while you're taking 18 them; that's not a problem. The problem is during withdrawal 19 because they have an anticonvulsive property. People actually 20 give certain benzodiazepines for certain type of seizure 21 disorders. When the drug is abruptly discontinued, some 22 people might have a tendency to have a convulsion. And there 23 were isolated reports of people going into the hospital who 24 were on other benzodiazepines, but no one had really 25 systematically studied it. And when we did study it, we found 55 1 that there were some EEG changes that happened when you 2 withdrew a benzodiazepine. 3 Q. Okay. Now, again, this is a number of a class 4 of drugs and that class of drugs had been established before 5 you developed your drug; right? 6 A. My drug was one of the last. There were tons of 7 them on the market when I developed mine. 8 Q. Was Lilly a first-of-its-kind drug? 9 A. Yes. Fluoxetine, to the best of my 10 understanding, there had never been a specific 5-HT blocker 11 approved in this country prior to this drug. 12 Q. So there was very little experience with other 13 types of this drug when this drug was being developed; is that 14 correct? 15 A. That's correct. 16 Q. Does that in your opinion place a greater duty 17 on this company to look into the problems that might be 18 occurring with this drug? 19 A. Yes. 20 MR. FREEMAN: Your Honor, we object. 21 JUDGE POTTER: Sustained. 22 MS. ZETTLER: Nothing further. Thank you. 23 24 25 56 1 FURTHER_EXAMINATION _______ ___________ 2 3 BY_MR._FREEMAN: __ ___ ________ 4 Q. I just have one question. The total number of 5 patients in your study when submitted in 1983 were how many 6 patients? 7 A. I don't recall that. 8 Q. It was less than 2,000, wasn't it? 9 A. I believe so. 10 Q. It was less than 2,000, you believe? 11 A. Yes. I believe it was less than 2,000, but I 12 don't recall the exact number. 13 JUDGE POTTER: Thank you very much, ma'am. You 14 may step down; you're excused. 15 Ladies and gentlemen. I haven't had you too 16 long, but because of my late start, this seems to be a 17 convenient time to take the morning recess. As I mentioned to 18 you-all before, do not permit anybody to talk to you about 19 this case; do not discuss it among yourselves and do not form 20 or express opinions about it. We'll stand in recess for 15 21 minutes. 22 (RECESS; BENCH DISCUSSION) 23 MS. ZETTLER: Larry gave me their additions and 24 objections to the Heiligenstein deposition. We're thinking we 25 may end up running a little bit short again today with Doctor 57 1 Brown. What I'd like to do, if you want to do it this way, is 2 come back -- go back and work on it and see if we can come to 3 some agreements and then come back either right at the lunch 4 break or right after the end of the lunch break and go through 5 these with you so we can have something ready after Doctor 6 Brown. 7 JUDGE POTTER: Okay. 8 MR. MYERS: If I'm going to have to 9 cross-examine this witness after lunch, I would certainly like 10 some kind of a lunch break. 11 JUDGE POTTER: Ms. Zettler, let me ask you this: 12 Can you see the end right now? When will your end be? 13 MR. SMITH: Maybe tomorrow. 14 MS. ZETTLER: Thursday for sure, maybe tomorrow. 15 And we're talking about anticipating finishing with Doctor 16 Brown around 3:30ish. 17 MR. MYERS: How long is the direct going to be? 18 Tell me how long the direct is going to take. 19 MR. SMITH: I think if we get started at 10:30, 20 I think we'll be finished by 12:30. 21 MR. MYERS: I will cross him for 45 minutes to 22 an hour, in that neighborhood. 23 JUDGE POTTER: Okay. Maybe we'll take a little 24 extra time at lunch because I would like to have Heiligenstein 25 as your plan for this afternoon. 58 1 MS. ZETTLER: Right. And we were anticipating 2 if we're running short of time, we'll start with him and then 3 we may not finish with him today. 4 JUDGE POTTER: Let's do it this way. You do 5 what you've got to do and, Mr. Myers, we won't take more than 6 a half hour of your lunch period to deal with Doctor 7 Heiligenstein. 8 SHERIFF CECIL: The jury is still unclear about 9 what a corrected copy is. 10 JUDGE POTTER: Can you-all agree on a 11 definition? 12 SHERIFF CECIL: And if you can speak up. 13 MS. ZETTLER: Okay. I'm done, but thanks. 14 JUDGE POTTER: Mr. Freeman? 15 MR. FREEMAN: Judge, let me show you what 16 happens. This is the document that comes to Lilly from the 17 investigators, the same thing that they have that has 18 "corrected copy" on it. There will be minor differences, for 19 example, where they didn't fill in the uric acid or something 20 of that nature. They'll call up the investigator and say, 21 "Did you do a uric acid check," and then the uric acid check 22 will be filled in and the complete thing, this and that will 23 be sent back to the investigator so that when the FDA comes to 24 do their audit, they can see what was initially sent in and 25 was sent to the FDA. 59 1 MS. ZETTLER: I have no problems with that 2 definition up to the point of when the FDA comes to look at it 3 because there's no testimony that this was done with 4 absolutely every case. 5 JUDGE POTTER: Someone has asked about the 6 corrected copy. When Lilly got a case-report form they would 7 sometimes check with the investigator, if the report appeared 8 incomplete or inaccurate, if after talking with the 9 investigator Lilly believed the report was incorrect or 10 incomplete, Lilly prepared a corrected copy, both the original 11 and the corrected copy were sent to the FDA. 12 MS. ZETTLER: Fine. 13 MR. FREEMAN: And I would like to introduce this 14 as the original so that they can -- 15 JUDGE POTTER: Mr. Freeman? 16 MR. FREEMAN: Excuse me just a minute, Judge. 17 JUDGE POTTER: Okay. 18 MR. FREEMAN: Okay. I made a misstatement. The 19 corrected copy goes to the FDA. The uncorrected copy is 20 maintained by the investigator, along with a corrected copy so 21 that they can do an audit, if they do an audit they can see. 22 MS. ZETTLER: I just don't want to get into this 23 audit routine, Judge. I mean, there is no reason to get into 24 the audit routine. 25 JUDGE POTTER: Wait just a second. The 60 1 corrected copy was sent to the FDA. 2 MS. ZETTLER: Both copies are maintained by the 3 investigator, period. 4 MR. FREEMAN: And by Lilly. 5 MS. ZETTLER: And by Lilly. That's fine. 6 MR. FREEMAN: Can we introduce this so they can 7 just look at it? 8 JUDGE POTTER: Well, I think if you want to do 9 it with one of your later witnesses to help explain it, you 10 can. 11 (BENCH DISCUSSION CONCLUDED; RECESS) 12 SHERIFF CECIL: The jury is now entering. All 13 jurors are present. Court is back in session. 14 JUDGE POTTER: Ladies and gentlemen of the jury, 15 one of you asked about the term corrected copy you've seen 16 stamped on some of those documents. The parties have 17 authorized me to tell you rather -- than to ask that question 18 of a particular witness, to tell you that when Lilly got a 19 case-report form, they would sometimes check with the 20 investigator if the report appeared incomplete or inaccurate. 21 If after talking with the investigator Lilly believed the 22 report was incorrect or inaccurate, Lilly prepared a corrected 23 copy of that report. The corrected copy was sent to the FDA; 24 however, both the original and the corrected copy were 25 maintained by Lilly, and the corrected copy was sent back to 61 1 the investigator to be maintained by the investigator along 2 with the original copy. 3 Mr. Smith, do you want to call your next 4 witness? 5 MR. SMITH: Yes, Your Honor. At this time we'd 6 call Doctor Alan Brown. 7 JUDGE POTTER: Sir, would you step down here and 8 raise your right hand, please. 9 10 ALAN BROWN, after first being duly sworn, was 11 examined and testified as follows: 12 13 JUDGE POTTER: Would you have a seat, sir. 14 Would you spell your first and last names and then pronounce 15 it loudly for the jury, please, and keep your voice up when 16 you're answering Mr. Smith's questions. 17 DOCTOR BROWN: A-L-A-N, B-R-O-W-N, Alan Brown. 18 19 EXAMINATION ___________ 20 21 BY_MR._SMITH: __ ___ _____ 22 Q. How old a man are you, Doctor Brown? 23 A. Excuse me? 24 Q. How old a man are you? 25 A. Forty-six. 62 1 Q. Where do you live? 2 A. In Dallas, Texas. 3 Q. And how long have you lived in Dallas, Texas? 4 A. Twenty years. 5 Q. What do you do for a living, sir? 6 A. I teach psychology at Southern Methodist 7 University. 8 Q. And how long have you been with the psychology 9 department at Southern Methodist University? 10 A. Twenty years. 11 Q. You, Doctor Brown, are being too modest, which 12 has not been one of the traits of our experts up to this 13 point. You are Chairman of the Department of Psychology at 14 Southern Methodist University, are you not? 15 A. Yes. 16 Q. I call you Doctor Brown. Is that because you 17 are a medical doctor or have some other degree that gives you 18 the right to be called Doctor Brown? 19 A. I have a Ph.D. degree. 20 Q. And what is that Ph.D. in, sir? 21 A. In psychology. 22 Q. Would you tell the jury about your educational 23 background, Doctor Brown, starting with when and where you 24 went to high school? 25 A. I went to high school at George Marshall High 63 1 School in McLean, Virginia, and from there I went to the 2 college of Wooster, in Wooster, Ohio, and graduated from 3 college with a bachelor's degree in psychology in 1969. From 4 there, I went for one year to the State University of New York 5 at Binghamton to serve as an assistant instructor of 6 psychology and also take more psychology courses. From there, 7 in 1970, I went to Northwestern University in Evanston, 8 Illinois, received a master's degree in psychology in 1972, 9 and a Ph.D. in psychology in 1974. 10 Q. While you were at Northwestern, did you teach at 11 that institution? 12 A. Yes, I did. 13 Q. All right. And did you teach the entire 14 four-year period of time that you were at Northwestern working 15 on your Master's and your Ph.D.? 16 A. No. 17 Q. All right. How much of that time was engaged in 18 teaching, Doctor Brown? 19 A. I taught three courses in the time I was at 20 Northwestern. After I received my Master's, I taught a course 21 in the Psychology of Thinking in 1972, and I also taught 22 Experimental Psychology in the evening division in 1973 and 23 1974. 24 Q. After you got your Ph.D. degree, did you go -- I 25 guess you went -- if you got it in 1974, you went straight to 64 1 Southern Methodist University? 2 A. Yes. 3 Q. And have you been a full-time professor at 4 Southern Methodist University since you joined SMU? 5 A. Yes. 6 Q. Did you start as a full professor at SMU or did 7 you go up the instructor, assistant professor ranks? 8 A. You begin at the assistant professor level and 9 usually spend six years at that rank and are considered for 10 tenure after six years. Then you're promoted to associate 11 professor and stay there until qualified or until the school 12 or department deems you qualified to be a full professor, and 13 I have achieved the rank of full professor. 14 Q. When did you achieve the rank of full professor, 15 Doctor Brown? 16 A. I believe that was in 1992. 17 Q. And when did you become chairman of the 18 department of psychology at SMU? 19 A. In 1992. 20 Q. And how many instructors, teachers and 21 professors are under you in the department of psychology at 22 SMU? 23 A. Approximately 13 professors -- full-time 24 professors and 4 to 6 adjunct professors. 25 Q. And do you have teaching assistants or 65 1 instructors under you, also, sir? 2 A. Yes. 3 Q. Can you give us an approximate number of how 4 many that would include? 5 A. In terms of under me directly, I have -- I 6 usually have a teaching assistant for each course I teach, and 7 the department has 20 to 25 teaching assistants across the 8 department with other professors. 9 Q. Doctor Brown, we've heard the term psychology, 10 psychiatry and medical doctor and Ph.D. all mentioned here 11 today or throughout this trial. What is basically the 12 difference in a psychiatrist with an M.D. degree and a 13 psychologist with a Ph.D. degree? 14 A. There's a difference, of course, in the training 15 they receive. A psychologist usually goes to graduate school 16 for four to five years and their training is essentially in 17 their area of specialty plus research methodology. A 18 psychiatrist goes to medical school and then specializes after 19 medical school for several years in a particular discipline. 20 Q. Do psychologists learn things about mental 21 disorders in their training? 22 A. Yes. 23 Q. And in their education? 24 A. Yes. 25 Q. Do psychologists treat patients with mental 66 1 illnesses? 2 A. Yes. 3 Q. Is that a particular branch of psychology? 4 A. A clinical psychologist is usually the type of 5 specialist that treats people that are having psychological 6 difficulties. 7 Q. That would be clinical psychologist? 8 A. Yes. 9 Q. Is there other branches of psychology? 10 A. There are a number of different subspecialty 11 areas within psychology, and would you like me to list some? 12 Q. Please. 13 A. There's subspecialties like social psychology, 14 which deals with behavior of groups; developmental psychology, 15 which deals with children; geriatric psychology, which deals 16 with older adults; cognitive psychology, which deals with the 17 way the mind works, memory, learning, thinking processes. 18 Those are some of the subareas in psychology. 19 Q. Is there a subarea or does psychology involve 20 the study of administration of tests and testing methods? 21 A. Those individuals are, if they specialize in 22 that, they are called psychometricians. 23 Q. All right. And does the practice of psychology 24 or do some psychologists deal with statistics? 25 A. They're usually psychologists that have training 67 1 in research methodology and statistics as a uniform part of 2 their graduate training. Most graduate programs require 3 between two and six courses in statistics, and statistical 4 applications for the awarding of the Ph.D. 5 Q. When you say research methodology, explain to 6 the jury what research methodology is. 7 A. The discipline of psychology, especially 8 academic psychology, requires you to engage in research in 9 addition to teaching. In order to maintain my job, I need to 10 publish quality research and be able to evaluate research, and 11 I need to publish that at a moderate rate throughout my career 12 in order for advancement. Most graduate programs in 13 psychology are geared towards having individuals trained in 14 research expertise and statistical analysis so that they have 15 the skills to maintain a job in a quality institution. 16 Q. Tell the jury specifically what type of training 17 you've had in research methodology. 18 A. As an undergraduate at the College of Wooster, 19 we had a rigorous training program in the design and analysis 20 of research. In fact, we were required to write approximately 21 ten different research projects, write them up, design them, 22 carry them out and analyze them as undergraduate students at 23 the College of Wooster. I also took two courses in statistics 24 in the psychology department; one was a basic course and one 25 was more advanced. At the State University of New York at 68 1 Binghamton, I elected to take another statistics course. At 2 Northwestern there were five statistics courses required in 3 order for the Ph.D. degree, and along the way, there were 4 numerous methodological courses usually designed as seminars 5 where we designed research, analyzed research and discussed 6 it, presented it, looked at the various flaws until research 7 did redesigns of various research projects. So I would say in 8 the graduate level, there were probably a total of ten courses 9 that I took which dealt directly with statistics and the 10 design of experiments, proper design and analysis of 11 experiments. 12 Q. Do you currently design and analyze experiments, 13 Doctor Brown? 14 A. Yes. 15 Q. And do you do that on a regular or irregular 16 basis? 17 A. On a regular basis. 18 Q. How long have you been designing and analyzing 19 experiments and testing? 20 A. I have been designing and testing research -- 21 original research projects, not part of course work but 22 designing original studies that I've thought of or 23 collaborated with people on since 1967. 24 Q. Has all of that involved application of 25 statistical principles to those tests? 69 1 A. Yes. 2 Q. Tell, specifically, us how much statistical 3 analysis training you've had. 4 A. To reiterate the course work, I've had two -- as 5 an undergraduate, two courses as an undergraduate student, one 6 course at the State University of Binghamton when I was an 7 assistant instructor, and five courses at Northwestern 8 University, all specifically statistical. 9 Q. So you've had eight courses in statistics? 10 A. Yes. 11 Q. Five of them at the graduate level? 12 A. The one at the State University of New York at 13 Binghamton was also at the graduate level. 14 Q. So six graduate-level statistics courses? 15 A. Yes. 16 Q. Do you teach statistics? 17 A. Yes. 18 Q. How long have you been teaching statistics? 19 A. For 20 years. 20 Q. Do you teach statistics specifically as it is 21 applied to psychological testing and experimental designs? 22 A. Yes. 23 Q. And research methodology? 24 A. Yes. 25 Q. Is statistics and research methodology 70 1 intertwined? 2 A. They are -- they are intimately intertwined 3 because if you do not have a good design, you can't have a 4 statistical test give you any good information. 5 Q. Why is that? Give us some examples of how the 6 design of a test or an experiment can affect statistics where 7 the statistics won't be meaningful or might be misleading. 8 A. When I teach a course to undergraduate students, 9 what I do is begin every class period with an example of a 10 particular statistical test that is inappropriate or a design 11 that's inappropriate, and I find this is a good vehicle to get 12 the student's attention. It's something they always remember 13 and comment back to me that this was the most engaging part of 14 the course. So what I will do is take something like a 15 commercial out of a newspaper or magazine, put it on an 16 overhead in front of the students and we'll discuss it. In 17 general, most of these involve a statistical analysis but 18 there is a flaw in the data design. So the students soon 19 realize that statistics are essentially meaningless unless 20 they're grounded in a firm foundation and that firm foundation 21 is a good design. 22 For instance, one of the studies that I present 23 is -- I don't know if you recall this, a few years ago there 24 was the Pepsi challenge. And the Pepsi challenge involved 25 having people taste-test Pepsi and Coke. Pepsi claimed that 71 1 people preferred Pepsi more often than Coke and in fact the 2 numbers bear that out. There was a significant preference, 3 significantly higher preference for Pepsi than Coke. 4 Q. You mean they tested maybe 1,000 people and 750 5 people chose Pepsi over Coca-Cola? 6 A. That's correct. Well, the statistics or the 7 numbers are true, they don't lie, but what the problem was was 8 the design of the study. And what they did is always present 9 the cup with Pepsi with an M on the front of it and the cup 10 with Coke with a Q on the front of it. 11 Q. You mean every time they administered the test 12 to those 1,000 people they had separate cups and each time 13 that cup had M for Pepsi and Q for Coke? 14 A. Yes. 15 Q. All right. 16 A. Now, of course, superficially, this may seem 17 like not a big issue, but what I pointed out to the students 18 and what they readily agreed to is that the letter M is 19 preferred over the letter Q. If you think of the associations 20 to the letter M, things like mother and more and milk, and you 21 have not very many good associations to the letter Q. Not 22 only are there bad associations like quick, quack, queer, but 23 it sounds harsh and M sounds very smooth. It's a regular 24 letter, it's symmetrical; Q is an irregular letter. 25 All these are very subtle biases, but pulling 72 1 that out you're left with statistics that are true, but a 2 conclusion that isn't; that is, you can't conclude that people 3 prefer Pepsi over Coke. What you can do is conclude, at the 4 best, that they may prefer M over Q or they may prefer Pepsi 5 over Coke. You don't know. You don't have the data. 6 Q. Because the design of that experiment or that 7 test had something else that was a factor involved; is that 8 what you're saying? 9 A. Yes. That's correct. 10 Q. That being the M versus Q? 11 A. Yes. 12 Q. Another quick example of how designs of 13 experiments or tests affect the validity of the statistics 14 that are the result of the test. 15 A. Another example that I give them is -- and this 16 is a case of sampling, selective sampling of data. There was 17 a statement by Tylenol recently that said doctors recommend 18 Tylenol to their patients more often than any brand of 19 aspirin. Now, that's true. That's a true statistic, that's a 20 not a lie, but the implication is that Tylenol is recommended 21 over aspirin more frequently. That's not true; it's 22 recommended over brands of aspirin. Subtlety in the wording. 23 If a doctor recommends Tylenol, they will say that they want 24 the patient to take Tylenol; if they want them to take 25 aspirin, they will say that. In fact, aspirin is recommended 73 1 considerably more often than Tylenol, but doctors don't say 2 the word Bayer, Bufferin, Anacin, they say take aspirin. So 3 that's another case where the statistics are true but they're 4 selective, they're taken out of context and so, in actuality, 5 they lie. 6 In fact, I recommend the book How to Lie with 7 Statistics to my students when I teach this course. It's a 8 cute little book, but it points out a lot of these flaws. 9 It's written by I believe a statistician who notes that the 10 numbers themselves don't lie, it's the way people use them and 11 the flaws in the experiments or the designs that are set up 12 that these statistics are applied to. 13 Q. All right. So your area, as I understand it, is 14 expertise in the area of design and methodology of experiments 15 or clinical trials for this case; correct? 16 A. Yes. 17 Q. And versus pure mathematical statistics? 18 A. Yes. 19 Q. You have, though, a wealth of statistical 20 background; is that right? 21 A. Yes. I have -- my training is statistics as 22 applied to psychological research. 23 Q. Some statisticians, I guess, progress through 24 the math department? 25 A. Yes. 74 1 Q. Have you taught statistics to those math 2 students? 3 A. Not specifically, not math students. 4 Q. Have you had math professors come in and try to 5 teach statistics to your psychology students, Doctor Brown? 6 A. That is a continuing struggle. 7 Q. Why? 8 A. As chairman of the department and as -- in my 9 capacity prior to chairman I was in an associate chair for six 10 years responsible for scheduling classes, and that was one of 11 the duties. And the difficulty we have with statisticians is 12 they have a very difficult time communicating principles to 13 students; they end up being more confused sometimes than 14 elucidated. The other problem is they have a difficult time 15 explaining the statistics with good real-world or 16 psychological examples. They tend to stick to the derivation 17 of the formulae rather than the application. 18 Q. So you keep the mathematicians out of your 19 psychology department; is that right? 20 A. I am eternally hopeful I will find some good 21 statisticians, and I have on occasion found some. 22 Q. But your Ph.D. is in psychology as opposed to 23 statistics? 24 A. Yes. 25 Q. But you are conversant in statistics? 75 1 A. Yes. 2 Q. And teach statistics at graduate level? 3 A. Yes. 4 Q. How many graduate-level statistics courses do 5 you teach or have you taught? 6 A. I have taught two different graduate level -- 7 no, three different graduate-level statistics courses, courses 8 that involve primarily statistics. 9 Q. Now, I have your CV, where I've got page after 10 page of writings that you've done about all kinds of 11 interesting stuff -- subjects such as cultural norms for items 12 in 30 toxignomic categories. Do you apply, though, statistics 13 to all of your papers? 14 A. Yes. 15 Q. Because are all of your papers basically 16 research projects? 17 A. Yes. 18 Q. Is it important to apply statistics to research? 19 A. Yes. It is critical. 20 Q. Is it important to apply the right statistical 21 method? 22 A. Yes. 23 Q. Is there a science and a particular field of 24 knowledge concerning the right statistics for the right test? 25 A. A subarea of psychology. 76 1 Q. Is a subarea of any kind of specialty, is it 2 important to be able to apply -- 3 A. Yes. 4 Q. -- the right statistical method to analyzing a 5 group of data? 6 A. Yes. 7 Q. And is it equally important or even more 8 important to know what the design of your clinical trial is or 9 your experiment before you can interpret any of the 10 statistical data concerning that experiment? 11 A. Yes. 12 Q. Doctor Brown, we have asked you to examine some 13 information in connection with Prozac, have we not? 14 A. Yes. 15 Q. And have you done that, sir? 16 A. Yes. 17 Q. Can you generally describe what data it was that 18 you examined, sir? 19 A. It was the clinical trials that Lilly had 20 various contract researchers carry out to determine whether 21 the medication was safe or had any side effects. 22 Q. All right. And did we first send you that 23 document that Lilly sent to the 1991 advisory committee that 24 had summaries and data concerning the clinical trial 25 experience of Prozac? 77 1 A. Yes. 2 Q. And was that the first thing you reviewed? 3 A. Yes. 4 Q. And later did we send you additional information 5 concerning facts, figures and matters pertaining to the Prozac 6 clinical trials and depression? 7 A. Yes. 8 Q. Generally would you describe that, sir? 9 A. Describe my impression? 10 Q. No. Describe what the data was that we sent 11 you. 12 A. It was research reports prepared by physicians 13 working for Lilly. It was summaries of suicidality, reports 14 of suicides. There were I guess in-house studies done for 15 Lilly, as well as the published varieties, meta analyses of a 16 collection of research projects done across various labs. 17 Q. Did you review the protocols or trial designs in 18 connection with the Prozac trials? 19 A. Yes. 20 Q. Okay. What is your understanding of what these 21 protocols were, Doctor Brown? 22 A. With respect to the entire sequence conducting 23 the research? 24 Q. What generally is a protocol in your impression 25 as a psychologist having to do with design, testing and the 78 1 statistical application of statistical principles to those 2 tests? 3 A. As I understand it, the protocol is the set of 4 procedures that are given to the physicians in order to 5 conduct the research project from the beginning to the end. 6 Q. All right. Now, based on the data that you 7 reviewed, have you come up with opinions concerning the Prozac 8 clinical trials, Doctor Brown? 9 A. There were several dimensions of the research 10 that struck me as being odd or insufficient. 11 Q. From a statistical standpoint or from a design 12 standpoint, Doctor Brown? 13 A. The primary problem I had was with the design of 14 the research. 15 Q. All right. What specifically was that problem? 16 A. There were numerous problems. Shall I enumerate 17 them? 18 Q. Yeah. Let's just start with what your first 19 criticism is of the design. I assume we're in the design area 20 at this time; correct? 21 A. Yes. Yes. The -- well, taking it sequentially, 22 one of the requirements, as I understand it, for subjects to 23 participate in the research project was that they not be 24 seriously suicidal, and those particular subjects were 25 excluded from consideration if the physician deemed that they 79 1 had a serious suicidal tendency. This I have difficulty with 2 because what you're doing is selecting out a segment of the 3 population. One of the things that we teach in research to 4 our students is that you have to be careful about what 5 population you sample from because you can only generalize 6 back to that same population. 7 Q. All right. Now, let's expand on that a little 8 bit, Doctor Brown. You say you can only generalize back to 9 the same subject of people that you've studied? 10 A. Yes. 11 Q. Explain that. 12 A. Well, let's say that if I wanted to do a 13 research project on memory with college students, I'll take it 14 out of my own realm, and I ended up sampling only blue-eyed 15 students, and I ran my experiment and found a particular set 16 of results from my manipulations. I can generalize my results 17 or conclude that my results hold for blue-eyed students; I 18 cannot conclude that they hold for all students because I have 19 excluded some. I have excluded brown-eyed students from my 20 sample. 21 Q. Well, could you make any -- based on your 22 example, could you make any analysis of whether or not 23 blue-eyed students were to become more sunburned than 24 brown-eyed students based on an analysis exclusively of 25 blue-eyed students? 80 1 A. No. 2 Q. Why is that? 3 A. You simply don't have the individuals you need 4 to draw those conclusions. They may behave very differently, 5 in very different ways than the sample that you drew. 6 Q. What specifically do we know about the 7 differences in collections of people that have blue eyes 8 versus brown eyes and their ability or susceptibility to 9 sunburn? 10 A. I'm sorry? 11 Q. Well, are blue-eyed people generally more fair 12 skinned? 13 A. Fair skinned, yes. 14 Q. Thus, more likely to become sunburned? 15 A. Correct. 16 Q. Any other examples that you can give us about 17 making sure that we draw the right conclusions from the 18 statistics by virtue of the clinical design? 19 A. Well, anytime you exclude a portion of the 20 population systematically, then the only conclusions you can 21 draw are with respect to that, having just the portion of the 22 population you worked with. You can never be sure what the 23 effect of your variable is on the excluded portion of the 24 population unless you directly test them. You can speculate, 25 but that's not good research. 81 1 Q. All right. Now, specifically, what is your 2 criticism about excluding out individuals who are seriously 3 suicidal from the Prozac clinical trials to draw some analogy 4 about depressed individuals? 5 A. The effects of the medication on individuals who 6 are not seriously suicidal may be different than the effects 7 of the medication on individuals that are seriously suicidal. 8 MR. MYERS: Excuse me, Your Honor. May I 9 approach? 10 (BENCH DISCUSSION) 11 MR. MYERS: I'm going to object to any testimony 12 being elicited from this Witness on the subject of effects or 13 possible effects of medication on patients or clinical trials 14 on the basis that, Number One, he's not a physician, thus he's 15 not qualified and there's been no disclosure that he's going 16 to make any statement about the effects of medication. I 17 think he needs to stick with what he's been put up for and 18 that is the design business. 19 JUDGE POTTER: In the questions so far that's 20 all he's done. 21 MR. MYERS: He's maybe starting down that road 22 and I just want an objection. 23 JUDGE POTTER: I mean, he's stayed within what 24 -- he's saying what can be shown and can't be shown is based 25 on the design of the program and not on his supposed knowledge 82 1 as a medical doctor, so objection is overruled. 2 (BENCH DISCUSSION CONCLUDED) 3 MR. SMITH: Go ahead, Doctor Brown. 4 JUDGE POTTER: You don't have to stay real close 5 to that microphone. What you need to do is keep -- there are 6 two systems in here; that one and the other one, and for our 7 purposes it's the brown one that counts. 8 You-all could hear everything, couldn't you? 9 You just looked uncomfortable. 10 DOCTOR BROWN: Well, I'm used to speaking in 11 microphones when I'm in public, so I wanted to make sure you 12 could hear me. 13 Q. You haven't ran for political offices, have you, 14 Doctor Brown? 15 A. No. 16 Q. Haven't had any papers published in Penthouse, 17 have you? 18 A. No. 19 Q. Go ahead. I just wanted to get that straight 20 before we got started. 21 A. You got me off track a little. Reframe the 22 question here. 23 Q. What's the problem, Doctor Brown, with drawing 24 conclusions concerning the effect of Prozac on depressed 25 people if you have excluded a group of those people who are 83 1 seriously suicidal from the outset of the clinical trial? 2 A. The results do not apply to a subsegment of the 3 population. And I guess to extrapolate that one step further, 4 if you're going to dispense the medication to all people who 5 are depressed without screening the seriously suicidal 6 individuals, then the results of your research do not apply to 7 the application of the drug. 8 Q. All right. So, do you have concern, then, about 9 whether or not that data you reviewed in the Lilly clinical 10 trials is applicable to the issue of whether or not Prozac 11 causes suicidality or violent-aggressive behavior? 12 A. It's inadequate to firmly conclude that Prozac 13 doesn't cause suicidality in depressed individuals at a 14 greater rate than a comparitor or placebo. 15 Q. Why? 16 A. You don't have the data to make that assertion. 17 You can conclude that it appears at least superficially in a 18 number of studies that there is no difference between Prozac 19 and a comparitor or Prozac and a placebo, but for a select 20 group of depressed individuals, not for all depressed 21 individuals. 22 Q. All right. So is what you're saying that data 23 can only be applied to particular groups within a larger 24 group? 25 A. Yes. 84 1 Q. And can't be applied to other groups? 2 A. Yes. 3 Q. Those groups that might have a risk of 4 suicidality or violent-aggressive behavior? 5 A. Suicidality specifically. 6 Q. All right. Was the design of the Prozac 7 clinical trials sufficient, then, to make or answer the 8 question of whether or not Prozac causes suicidal behavior in 9 individuals? 10 A. It is not a definitive design to answer that 11 question. 12 Q. What would have been appropriate to face that 13 question, or to address that question? 14 A. To really address the question correctly, the 15 clinical trials need to draw a sample of individuals who are 16 going to be administered that medication in the real-world 17 setting. 18 Q. All right. Lilly claims here that that can't be 19 done for what appears to be a logical reason, that is, you 20 don't want people who are seriously suicidal in clinical 21 trials on an outpatient basis; they need to be hospitalized. 22 Is that reasonable? 23 A. If I were to design the research, you would need 24 to include those individuals; however, however you could 25 conduct the research it would be theoretically mandatory to 85 1 include those individuals in the project. 2 Q. All right. Or if you don't include them from an 3 academic, practical and realistic standpoint, you ought not to 4 make any conclusions or you ought to advise in your research 5 that this data can't be applied to a particular set of 6 individuals; is that what you're saying? 7 MR. MYERS: Excuse me, Your Honor. I have an 8 objection. That's leading and suggestive of an answer. 9 JUDGE POTTER: It is leading. Sustained. 10 Q. Do you have an opinion if you do exclude a 11 particular group what should be done about that? 12 A. The conclusions that you draw must specifically 13 be limited to the group that you sampled from. 14 Q. And should you tell people about that? 15 A. And people should be made aware of that. 16 Q. All right. Now, did you go ahead and look at 17 that data that was supplied there to come to any other 18 conclusions? 19 A. Yes. 20 Q. All right. What did you look at or what were 21 your findings in respect to that? 22 A. If I could have another comment on the screening 23 criteria before I get into the actual design. 24 Q. Yeah. Okay. 25 A. I believe in reading the materials that people 86 1 were also excluded if they had had a -- if they had had 2 problems with substance abuse or with alcohol abuse in the 3 year prior to the study. 4 Q. What difference would that make in depressed 5 individuals? 6 A. It would exclude still another subsegment of 7 depressed individuals. 8 Q. Why? 9 A. One of the characteristics of depression is that 10 people do turn to substances in order to ameliorate the 11 depressive state prior to getting help. There is a number of 12 people that turn to alcohol or drugs in order to -- in order 13 to salve the depressive state and this is one of the 14 characteristics. So if those people are excluded, then you 15 have still another subsegment of depressed people that are 16 excluded from your study and you can't generalize your outcome 17 back to those individuals. 18 Q. All right. Is there any other criticisms that 19 you have concerning the -- what I guess we would be calling 20 the selection of individuals to be in the clinical trials? 21 A. The front-end selection, there's just those two 22 problems on that phase. 23 Q. All right. Now, do you want to go into now, 24 Doctor Brown, particular things you found in reviewing the 25 Lilly clinical trial data that caused you some concern? 87 1 A. One difficulty I discovered was if you look at 2 the assignment of individuals to the different groups, how 3 people are placed in the Prozac, the placebo group and the 4 comparitor drug, say the imipramine group, the claim is there 5 was random assignment of these individuals to the group. They 6 would take a depressed individual and randomly assign them 7 through a specific process so that they were without bias 8 placed in one of those three groups, and this is absolutely 9 essential for good research. The problem is, in looking at 10 the baseline measures of these individuals, I found a pattern 11 across a number of studies that seemed to indicate that there 12 was some form of bias where the people that were better off 13 got put into the Prozac group; the people that were worse off 14 got put into the placebo or the comparitor drug group. 15 Q. All right. Let me stop you there. Are you 16 saying that you have seen something in the data that you've 17 reviewed that indicates that the people who got Prozac in the 18 clinical trials may have been less depressed than the people 19 that got placebo or comparitor drug? 20 A. Yes. 21 Q. Is that significant, Doctor Brown? 22 A. There are several ways to examine the data, and 23 I examined them, and at least two of the ways that I looked at 24 it, there was a significant difference across studies. 25 Q. I'm talking about significant from a design 88 1 standpoint. Is that important to know that you may be 2 starting off looking at a situation where you have people 3 taking Prozac that aren't as depressed as people taking the 4 comparitor drug or placebo? 5 A. Yes. 6 Q. Why? 7 A. If you start out with people at a different 8 level of depression, then you really have qualitatively 9 different subgroups of people in your groups to start with. 10 So any differences you find across your groups could either be 11 due to where they started to begin with in the absence of any 12 treatment or it could be due to your treatment; you don't 13 know. You are left -- 14 Q. But you're not starting people off at the same 15 spot; is that what you're saying? 16 A. Yes. 17 Q. Specifically, did you see that in connection 18 with these individuals' baseline HAMD-3 scores? 19 A. Yes. 20 Q. All right. 21 (BENCH DISCUSSION) 22 MR. MYERS: This is an exhibit from his 23 deposition and I've been shown it, but my objection is to its 24 admission into evidence. It's not evidence; it's just 25 demonstrative of what his opinions are, but it's not evidence 89 1 as such. I certainly have no problem having it displayed to 2 the jury, but I don't think it should be passed out as 3 evidence. 4 MR. SMITH: We've identified it as something to 5 be introduced into evidence and presented into evidence, and 6 it was discussed in his deposition as something he's basing 7 his opinion on. It's a summary is basically what it is. It's 8 a summary of the data. 9 JUDGE POTTER: Mr. Myers is correct. It is just 10 a typed-up version of his testimony, and I have kept out -- I 11 forget. Somebody here had a typed-up version of their 12 testimony that I kept out. I can't remember which side it 13 was, but I think on certain limited things, graphs, charts 14 that are very helpful to a jury, they can be introduced as an 15 exhibit even though they don't have evidentiary value in 16 themselves; they're more demonstrative things. So I'm going 17 to overrule the objection. 18 (BENCH DISCUSSION CONCLUDED) 19 Q. Doctor Brown, I've handed you Exhibit No. 179. 20 Can you identify that, sir? 21 A. This is a summary -- what I'll call a meta 22 analysis or a group of studies considered together. 23 MR. SMITH: All right. We would offer 24 Plaintiffs' Exhibit 179, Your Honor. 25 JUDGE POTTER: Be admitted. 90 1 SHERIFF CECIL: (Hands document to jurors). 2 Q. All right. Doctor Brown, I have a blowup of -- 3 can you see it? 4 A. Yes. 5 Q. -- of the exhibit. Let's give the jury some 6 background of what this is. As I understand it, you looked at 7 a number of studies; is that right? 8 A. Yes. 9 Q. How many? 10 A. There are 78 studies represented on this chart. 11 Q. All right. And did you -- was that studies that 12 had been described in the Lilly material that was submitted to 13 the 1991 PDAC meeting? 14 A. Yes. I believe so. 15 Q. And so you just took this from Lilly's own data; 16 is that right? 17 A. Yes. 18 Q. All right. I see here on one line we have 19 number of studies and then another line the graphs; is that 20 right? 21 A. Yes. 22 Q. All right. What did you find in looking at 23 these 70-something studies and what specifically were you 24 looking at in these studies? 25 A. As I reviewed the data the first time, I noticed 91 1 a suspicious pattern across studies, and that was it seemed to 2 be an unusual distribution of mean HAMD-3 scores. 3 Q. Now, the HD-3 score is that score on 4 suicidality, is it not? 5 A. Yes. That is the specific item off of the 6 Hamilton depression test that focuses on suicidality. 7 Q. Of those 21 or 17 questions in the Hamilton 8 Depression Inventory, this is Question Three? 9 A. Yes. 10 Q. Of the 0, 1, 2, 3, 4; is that right? 11 A. Yes. 12 Q. All right. 13 A. And I focused on this because this particular 14 piece of data was presented in all of these research studies. 15 The pattern that I found was that across the studies there 16 seemed to be an unusually high number of studies where the 17 HAMD-3 or the suicidality item, the mean was lower for 18 individuals in the Prozac group than individuals in the 19 comparitor or placebo group. 20 Q. All right. Let me see if I understand that. 21 When you say mean, what is mean? 22 A. That's the average of the HAMD-3 scores for 23 individuals in that group. 24 Q. Okay. So it would be 0, 1, 2, 3, 4, and it 25 would be adding up those and dividing by 5, I guess, to get 92 1 the average? 2 A. No. It would be dividing -- taking the HAMD-3 3 for each patient and then dividing by the number of patients 4 after you sum it across patients to get a mean for that group. 5 Q. All right. Okay. So what did you find when you 6 looked at that item on suicidality specifically? 7 A. I found that in a large number of studies the 8 individuals in the Prozac group were less suicidal than the 9 individuals in the comparitor group. There were three 10 different outcome possibilities, one is that the average for 11 people in the Prozac group was lower than the average in the 12 comparitor group. Another possibility is that the average was 13 higher and then, of course, the third is that they're equal. 14 So that covers all possibilities when you have -- when you're 15 comparing two different groups. 16 Now, in an ideal world where you had subjects 17 truly randomly assigned to conditions, what you would expect 18 is that the groups would always be exactly the same. Now, 19 that doesn't happen, and what you usually find is you'll have 20 some that are the same, some that are lower, some that are 21 higher in terms of the way the groups split. But you should 22 expect the way the less-than/greater-than comparisons fall 23 out, they should be about the same. 24 Q. So these should be approximately equal; is that 25 what you're saying? 93 1 A. Well, at least the two bars on the left. The 2 one on the extreme left and the one next to it in the middle, 3 those should be the same. 4 Q. All right. What are these bars? 5 A. Those bars -- the bar on the left indicates that 6 40 out of these 78 comparisons yielded the Prozac group lower 7 than the comparitor. 19 -- in the middle bar, 19 of the 8 studies indicated the Prozac group was higher than the 9 comparitor and in 19 outcomes the two groups were equivalent. 10 Q. Okay. Said another way, would this mean that 11 the Prozac group was -- had lower HAMD-3 scores, therefore, 12 less suicidal? 13 A. Yes. 14 Q. At baseline? 15 A. At baseline, to begin with. 16 Q. The others, the amount that were -- where Prozac 17 had a higher baseline was 19? 18 A. Yes. 19 Q. And where they were actually exactly equal in 20 the studies there was 19? 21 A. Yes. 22 Q. As a statistician from a statistical standpoint, 23 is that disparity significant to you? 24 A. Yes. 25 Q. Explain why. 94 1 A. You can do a statistical test to look at the 2 probability of this type of outcome happening by chance, and 3 the statistic is a Chi Square test. And this suggestion that 4 the -- this particular pattern is -- is not one that would be 5 produced by chance factors alone in terms of the groups being 6 inequal in both directions. 7 Q. So you're saying from a statistical standpoint 8 this just didn't accidentally happen? 9 MR. MYERS: Excuse me, Your Honor. I think 10 that's a little bit leading and again suggesting the answer. 11 JUDGE POTTER: Sustained. 12 Q. What are you saying from a statistical 13 standpoint about this? 14 A. The groups were not randomly assigned at 15 baseline. This does not mean that all of the studies were 16 flawed in this way, but a certain number appear to be flawed 17 in this way, because this type of outcome, this type of 18 distribution of baseline HAMD scores is unlikely due to 19 chance. 20 Q. Does this mean -- does this chart mean that it 21 would appear from these 70 something -- on these 70-something 22 studies that the Prozac people started out less depressed, 23 less suicidal than those people on comparitors? 24 A. Yes. 25 Q. All right. Anything else about this chart we 95 1 need to cover? 2 A. No. 3 Q. Did you review any other data or did you -- I 4 mean, did you take this data alone as conclusive, that there 5 was a problem here that might indicate that the Prozac people 6 were less depressed or less suicidal than the others? 7 A. There were other pieces of data that were 8 provided in some of the other research projects. 9 Q. All right. Such as what? 10 A. One piece -- another piece of data was that the 11 percent of individuals with secondary psychotic symptoms was 12 higher in the nonProzac group, the comparitor group than the 13 Prozac group, and I believe this was Bremner's study. 14 Q. Okay. Before we get away from the HAMD-3, did 15 you find anything about the number of individuals who had no 16 suicidal ideation? 17 A. Yes. 18 Q. Tell the jury what you found out in that 19 connection. 20 A. There was a summary of the -- I believe it's 21 Bosomworth had provided some data which looked at the 22 individuals broken down by each of the separate HAMD ratings. 23 Now, the HAMD scale is -- zero on the HAMD means that there's 24 no suicide -- HAMD-3 means there's no suicidality; a 1, 2, 3 25 or 4 means that there is some suicidality in progressive 96 1 severity. 2 Q. Do you have any comment about that as a 3 measurement of suicidality, Doctor Brown? 4 A. It's -- it seems to be the most sensitive 5 dimension of that scale would be the presence versus the 6 absence of suicidality. So the clearest demarcation is from 7 zero to one and above. Now, from one to four the 8 differentiations become a little more vague and subjective, 9 but the clearest indicator, the cleanest indicator to me is 10 people with a zero at baseline. 11 Q. Because it's totally absent? 12 A. Yes. 13 Q. And what did you find? 14 A. I found again evidence that the individuals in 15 the Prozac group were much more likely to have a zero at 16 baseline than the individuals in the comparitor or placebo 17 group. 18 Q. You mean there were more individuals that 19 started off on the clinical trial that weren't suicidal at 20 all? 21 A. Yes. 22 Q. Can you identify exhibit -- Plaintiffs' Exhibit 23 180, Doctor Brown? 24 A. Yes. This is the percent of the patients in the 25 data summarized by Bosomworth that had a zero -- HAMD-3 score 97 1 of zero at baseline; in other words, they were not suicidal to 2 begin with. 3 MR. SMITH: All right. I'd offer Plaintiffs' 4 Exhibit 180, Your Honor. 5 JUDGE POTTER: Be admitted. 6 SHERIFF CECIL: (Hands document to jurors). 7 Q. Okay. Now, can you tell us what group of people 8 this is? Is this all the clinical trial data? Is this the 9 same 78 studies that you were looking at earlier? 10 A. I am not sure. I could point out the summary of 11 that. It was from that same packet. 12 Q. All right. So it would be the 78 studies. It 13 would be the same -- 14 A. Probably. Sometimes it was unclear in the 15 documents provided by Lilly to unpack that. 16 Q. All right. Okay. So, what did you do here? 17 What does this graph represent, Doctor Brown? 18 A. This represents the percent of the subjects in 19 each of the three groups who had a zero on the HAMD-3 at the 20 start of the study. For instance, I believe it's about 36 21 percent of the individuals in the Prozac group had a HAMD-3 of 22 zero, which means they were not suicidal at the start of the 23 study. And comparing that with, say, to the placebo group, I 24 believe that was about 28 percent of those individuals had a 25 HAMD-3 score of zero, indicating they were not suicidal and, 98 1 in the tricyclic group, it was even lower. The percent was, 2 it looks, I believe, about 22 percent in the tricyclic group. 3 This suggests again that the individuals in the Prozac group 4 were better off, less suicidal as a group than the individuals 5 in the other two conditions. 6 Q. As does this? 7 A. Yes. 8 Q. This is the percentage of individuals who had no 9 suicidality whatsoever; is that right? 10 A. Correct. 11 Q. This is the number of studies in which the 12 individuals that had lower baseline were assigned to Prozac? 13 A. Correct. Those are group averages on that. 14 Q. All right. Anything else about this graph 15 that's significant to you, Doctor Brown? 16 A. No. Other than the conclusion that the groups 17 differed to begin with. 18 Q. And was this a problem from an experimental 19 design standpoint? 20 A. Yes. It's a major problem. 21 Q. Why? 22 A. Because you can't tell -- if there is a 23 difference or a lack of difference at the end of your 24 research, you can't tell what to attribute it to because 25 people are different to begin with in the groups. And if 99 1 they're different to begin with, then you cannot conclude with 2 any surety what effect your treatment has or what effect it 3 doesn't have. 4 Q. All right. Did you look at anything else or did 5 you see any other data that would indicate that there were a 6 difference among the Prozac versus other treatment group that 7 would indicate that the individuals on Prozac were less likely 8 to be as severely depressed? 9 A. There was -- in looking at Protocol 27, there 10 was an accounting of individuals with single-episode versus 11 recurrent depression. 12 Q. All right. Now, when you say single-episode 13 versus recurrent depression, give the jury the benefit of what 14 that is. 15 A. As defined by Lilly and is commonly defined, 16 people who have had a single depressive episode have had one 17 experience, one documented experience or event of a depressive 18 episode. Those people who have had two or more depressive 19 episodes are in the recurrent or the multiple episode group. 20 Q. Is the recurrent likely to be more depressed as 21 a group than the single episode as a group? 22 MR. MYERS: Excuse me, Your Honor. I have a 23 matter to take up with the Court. 24 (BENCH DISCUSSION) 25 MR. MYERS: He has now gone over the status 100 1 design. He's asking whether the single or recurrent episode 2 are more or less depressed. I object to that; he's not a 3 psychiatrist. 4 MR. SMITH: He's a Ph.D. psychologist, and 5 that's what Lilly said in connection with this data that 6 they're reflecting. 7 JUDGE POTTER: I'm sorry, Mr. Smith. Say that 8 again. 9 MR. SMITH: In other words, he took it out of 10 the PDAC data, and there Lilly said single-episode incidences 11 of depression are more likely to be less depressed and have 12 recurrent episodes. 13 MR. MYERS: The jury can make whatever 14 conclusion they want from what's in that document. The point 15 is this man is not qualified to decide whether it's single or 16 recurrent and whether they're less depressed or not. 17 JUDGE POTTER: This to me is something fairly 18 basic. I'm going to let him say that. I'm not sure the 19 document you're talking about is in evidence. You-all may 20 have kicked it around, but is that document in evidence? 21 MR. MYERS: Yes, sir. That document went in 22 through Doctor Leigh Thompson. 23 (BENCH DISCUSSION CONCLUDED) 24 Q. You can answer the question and I'll repeat the 25 question for you, Doctor Brown. As a group, from a Ph.D. 101 1 psychologist's standpoint, are individuals who have a 2 recurrent episode of depression more likely to be more 3 depressed than individuals that have had only a single 4 incidence of depression? 5 A. Of course it depends on the individual, from 6 individual to individual and the type of depression, but in 7 terms of the behavioral realm in general, anytime a behavior 8 is exhibited more than once, you have to assume that the 9 pervasiveness or the seriousness of that behavior is more so 10 than when you exhibit that one time. 11 Q. All right. I've handed you what's been marked 12 as Plaintiffs' Exhibit 181, Doctor Brown, and I'll ask you if 13 you can identify what that is. 14 A. This is the data from the Protocol 27, five 15 studies which were presented in documents from Lilly, and this 16 excludes Cohen. The data here is collapsed across all five 17 studies, and it reflects the percent of subjects in each of 18 the three groups who have single-episode depression. 19 MR. SMITH: We'd offer Plaintiffs' Exhibit 181, 20 Your Honor. 21 JUDGE POTTER: Be admitted. 22 SHERIFF CECIL: (Hands document to jurors). 23 Q. Okay. Explain to us what Exhibit 181 is, Doctor 24 Brown. 25 A. The subjects in each of the studies were 102 1 assessed in terms of the type of depression that they had at 2 the onset of the study, the research. And subjects were 3 classified as to whether they had single-episode or recurrent 4 depression, so an individual would fall into one of those two 5 classifications. Here I've just plotted the percent of 6 subjects who have single-episode depression, which is the 7 moderated form of depression. It's a more mild form, at least 8 as a group you can make that assumption, even though you can't 9 make it necessarily on a person-by-person basis. The 10 percentage of individuals who have single-episode depression, 11 as you can see, it comprises a larger percentage of the group 12 of Prozac patients than single-episode depression in either 13 the imipramine or the placebo group. 14 Q. All right. Is that significant to you when you 15 compare it with the baseline HAMD-3 scores of zero and the 16 mean HAMD-3 scores being less than the Prozac group? 17 A. Yes. 18 Q. What question does that raise in your mind, 19 Doctor Brown? 20 A. It's converging evidence -- what we call 21 converging evidence in research. It's another piece of 22 evidence looked at another different way that suggests the 23 overall conclusion that the Prozac group was better off, less 24 depressed on the average, than individuals in the other 25 conditions. 103 1 Q. This is only for those patients in Protocol 2 No. 27? 3 A. Yes. 4 Q. Did you not have any data from the other 5 studies? 6 A. No. The way that Lilly provided the data was 7 not consistent across all the research that I reviewed. 8 Q. You mean in the way they provided it in that 9 material that was submitted to you? 10 A. Yes. So I could not find this data in other 11 research summaries. 12 Q. All right. Anything else of this converging -- 13 what you called converging evidence or converging data that 14 caused you concern or was more evidence that the Prozac group 15 might have been better off to start with? 16 A. There was some evidence in I believe the Bremner 17 study, which looked at -- actually provided HAMD total scores 18 for each individual in their -- in their project, research 19 project. And what this did is suggest again a pattern of 20 individuals who are less depressed overall to be in the Prozac 21 group relative to the comparitor. 22 Q. Doctor Brown, can you identify what's been 23 marked as Plaintiffs' Exhibit 183, which was Exhibit 6 to your 24 deposition? 25 A. This is the number of subjects in the Bremner 104 1 study who fell into each HAMD total range. 2 Q. The Bremner study was a relatively small study; 3 is that right? 4 A. I believe so. I don't know exactly how many 5 subjects. 6 Q. Well, I guess we could add it up by looking at 7 your graph. 8 A. Correct. 9 MR. SMITH: All right. We would offer Exhibit 10 183, Your Honor. 11 JUDGE POTTER: Be admitted. 12 SHERIFF CECIL: (Hands document to jurors). 13 Q. Okay. Is this graph reflective of the baseline 14 HAMD scores in the Bremner study? 15 A. Yes. 16 Q. And you have it broken down into total HAMD 17 scores at baseline? 18 A. Yes. 19 Q. Is it your understanding that before patients 20 are put on the clinical trials, they come in and take the HAMD 21 score a couple of times in order to establish where they are 22 from a depressive standpoint? 23 A. My assumption is that they are administered it 24 prior to research. 25 Q. And then they get a baseline after they've done 105 1 the placebo washout and things of that nature? 2 A. Yes. 3 Q. And the Hamilton Depression Scale ordinately 4 goes up; is that right? 5 A. Yes. The higher the scores, the more depressed 6 the individual is. 7 Q. All right. So if I had a 25 and you had a 50 on 8 the HAMD score, what could be said about that, Doctor Brown? 9 A. The 50 would be -- indicate a greater depression 10 than the 25. 11 Q. And what does this exhibit show in connection 12 with the -- would this be severity of depression to some 13 extent? 14 A. Yes. 15 Q. All right. What does it show? 16 A. Well, the reason I plotted this is I was curious 17 to see if there was a pattern at both the low and the high end 18 for an inequity between the groups. This was the only study 19 that had the actual HAMD totals for individuals in the groups. 20 And so I plotted this out, and it appears to me that there is 21 a slight bias at both ends, indicating that at the low end, 30 22 to 33, the assignment of subjects to the groups was biased 23 slightly in favor of fluoxetine over imipramine, and at the 24 high end it was biased in the other direction. 25 Q. All right. 106 1 A. That the individuals who were more severely 2 depressed at the high end tended to be in the imipramine group 3 rather than the fluoxetine group. 4 Q. Okay. Well, what about these areas here where 5 they're exactly the same in 34 to 37 and actually there's more 6 patients in the Prozac group here? 7 A. That's correct. 8 Q. Why would you consider those in your analysis, 9 Doctor Brown? 10 A. Those are also relevant. If you take -- what I 11 was looking for is whether there were nonequivalents in the 12 extremes because that's where you tend to find a bias, at the 13 low and the high ends more particularly. 14 Q. All right. So you can put somebody that's 15 barely depressed or somebody that's severely depressed. 16 You're saying in this particular study what? 17 A. That there was a tendency to put the very 18 severely depressed in the imipramine group rather than the 19 fluoxetine because those -- there's 1 individual out at the 42 20 to 46 range in the fluoxetine end, 4 individuals in the 21 imipramine group. 22 Q. All right. Anything else of significance about 23 this, Doctor Brown? 24 A. No. 25 Q. Did you in looking at the data, especially from 107 1 Doctor Bremner, look at incidences of secondary psychotic 2 diagnoses? 3 A. Yes. 4 Q. Why did you do that, Doctor Brown? 5 A. That struck me, as reading through that, that 6 there was quite a disparity between the groups in terms of the 7 secondary diagnosis. 8 Q. Again, was this Bremner group the only group 9 that you had data on concerning the total HAMD baseline scores 10 and information concerning the baseline or the other -- second 11 diagnoses? 12 A. Yes. Yes. That was the only study in which 13 these two types of data were provided. 14 Q. Can you identify Exhibit 182? 15 A. These are the data from the Bremner study with 16 respect to the percentage of patients in each group who had a 17 diagnosis -- a secondary psychotic diagnosis. 18 Q. When you say secondary psychotic diagnosis, what 19 do you mean? 20 A. That's a psychological dysfunction in addition 21 to the depression. 22 Q. In other words, they had other mental disorders 23 in addition to depression? 24 A. Yes. 25 Q. Do you remember whether or not the clinical 108 1 trials had any types of prohibition against having individuals 2 with secondary psychotic disorders in the clinical trials? 3 A. I don't recall specific instructions. 4 Q. All right. Go ahead. Explain this chart, which 5 is Exhibit 182. 6 A. This suggests to me that the -- again, the 7 Prozac group seems to be relatively better off than the 8 imipramine group. 9 MR. SMITH: We'd offer Exhibit 182, Your Honor. 10 JUDGE POTTER: Be admitted. 11 SHERIFF CECIL: (Hands document to jurors). 12 Q. Now, can you see this, Doctor? Well, I don't 13 guess you have to see it since you've got it in front of you. 14 Can you explain what Exhibit 182 is, Doctor, what is shown? 15 A. This is the percent of patients in the Prozac 16 and in the imipramine group who had a diagnosis, secondary 17 psychotic diagnosis in the Bremner study. 18 Q. Okay. So there was less people with secondary 19 psychotic diagnosis in the Prozac group and more people in the 20 imipramine group; is that what you're saying? 21 A. Yes. A relatively lower percentage of 22 individuals in the Prozac group had this secondary diagnosis 23 compared to the imipramine group. And then concluding one 24 step away from that, it's more evidence that the individuals 25 in the Prozac group are relatively better off than the 109 1 comparitor. 2 Q. What does this then tell you, Doctor Brown, 3 concerning the statistical data derived from the Prozac 4 clinical trials? 5 A. It makes me suspicious that the -- that you can 6 draw any strong conclusions about any outcome of this 7 particular research, because if the individuals are not 8 comparable to start with, then any conclusions drawn at the 9 end of the research are suspect in terms of their validity or 10 their applicability to depressed individuals. 11 Q. Do you have any explanation, Doctor Brown, as to 12 why the individuals on Prozac in those studies you reviewed 13 would have lower baseline HAMD-3 mean scores, would have more 14 instances of zero findings of suicidality, would have a 15 situation where they would have less instances of secondary 16 psychotic features, where they would have more instances of 17 single episodes of depression versus recurrent episodes of 18 depression? How could that be if the Prozac clinical trials 19 were supposed to be truly randomized? 20 A. I don't have an explanation. 21 Q. Does it appear from your analysis that there was 22 true randomization in the Prozac clinical trials? 23 A. It would be very difficult to believe that. 24 Q. By virtue of what you've shown us here this 25 morning? 110 1 A. Yes. 2 Q. Does that cause you concern as a research Ph.D. 3 and an individual knowledgeable in research testing and 4 research methodology and test design and statistics? 5 A. Yes. 6 Q. Why? 7 A. If I submitted a research project with this type 8 of inequity at baseline, I would probably have the article 9 rejected with the admonition to do it again, and if you have 10 an equality at baseline, then we'll look at your outcome. But 11 if you have an inequal -- unequal groups to begin with, then 12 you cannot make valid scientific conclusions based on any 13 differences across those groups as attributed or not 14 attributed to your treatment. 15 Q. Is there any way to generalize back to how this 16 drug will work on the general depressed population when you 17 have a situation where the people in the clinical trials 18 didn't start off at the same spot? 19 A. There's no good way to do that, to generalize 20 back, based on this data. 21 Q. Did you have an occasion to review instances of 22 concomitant medications administered to patients in the Prozac 23 clinical trials, Doctor Brown? 24 A. Yes. 25 Q. And what study did you look at in that? 111 1 A. The concomitant medications were detailed in 2 Protocol 27, the five studies, excluding Cohen, in that group 3 of studies. 4 Q. You say excluding Cohen. Why were you excluding 5 Cohen? 6 A. Well, it appeared that that study was suspect 7 from several angles in the literature that I read. 8 Q. And Lilly excluded Cohen? 9 A. Yes. Lilly did, too. 10 Q. Even though he was one of their investigators; 11 correct? 12 A. That's right. 13 Q. Why was -- from a design and methodology 14 standpoint and as a Ph.D. psychologist, is it important to you 15 to look at the use of concomitant medications in the Prozac 16 clinical trials, Doctor Brown? 17 A. Whenever you run a research project, it's 18 critical that you have the conditions of the groups exactly 19 the same except for the independent variable that you 20 manipulate. If that's not true, then any outcome is -- any 21 outcome of your manipulation may be due to other variables 22 that occurred at the same time, and that's called a 23 confounding variable. 24 Q. Okay. A confounding variable, then, is what, 25 sir? 112 1 A. It's one that may produce the effect rather than 2 the variable that you think itdoes. If I could go back to the 3 Coke/Pepsi example, the manipulated variable was supposedly 4 the Coke and Pepsi; a confounding variable in that study was 5 the M and the Q. Now that's an easy one to see because that 6 is -- that outcome could be due to other people's preferences 7 for different letters or preferences for flavors; you can't 8 tell because they both were varying at the same time. It 9 wasn't a clean study. 10 And the same thing holds here, where you have 11 the independent variable or the one that you're trying to 12 manipulate and hold in specifically tightly in your design as 13 medication. That should be the only thing that is different 14 across your Prozac, your imipramine and your placebo groups. 15 Everything else should be as close to being identical as you 16 possibly can make it, and that involves not allowing other 17 medications to enter into the picture. 18 Q. Would you be especially critical if the 19 medication that was being administered was a medication that 20 also acted on the behavior and mood of the subjects in the 21 test? 22 A. Yes. 23 Q. Can you identify what's been marked as 24 Exhibit 184, Doctor Brown? 25 A. This is the percent of subjects in Protocol 27 113 1 who received concomitant medications of some sort at some 2 point in the clinical trials, and this is pictured separately 3 for each of the three groups. 4 MR. SMITH: We'd offer Plaintiffs' Exhibit 184, 5 Your Honor. 6 JUDGE POTTER: Be admitted. 7 SHERIFF CECIL: (Hands document to jurors). 8 Q. Now, explain to us what Exhibit 184 is, Doctor 9 Brown. 10 A. For each of the three groups, the Prozac, 11 imipramine and placebo groups, a certain percent of the 12 subjects in each of those groups was given other medication of 13 some sort at some point in the clinical trials, and this 14 represents the percent of subjects that were administered 15 other medication during the period, the clinical trial period. 16 And as you can see, the Prozac group was administered -- at 17 least percentagewise, a higher percentage of the individuals 18 in the Prozac group received other medication during that -- 19 during the clinical trial period than individuals in the 20 imipramine or the placebo group. 21 Q. Have you been able to review the data on all the 22 patients in all the clinical trials to determine what 23 percentage of those patients got concomitant medications? 24 A. The only -- I believe the only place that this 25 information is provided is in Protocol 27. That's the only 114 1 place that I found this information provided. 2 Q. All right. Now, to be clear, this is any 3 concomitant medication? 4 A. Yes. 5 Q. And according to Doctor Lord, I guess -- I know 6 you didn't hear Doctor Lord's testimony, but would this 7 include things like aspirin for headaches, heart medicine for 8 people that happen to have heart problems and things of that 9 nature? 10 A. Yes. It included -- I just did a simple count 11 of the number of administration of medications. 12 Q. Does it include how often the medication was 13 given? 14 A. No. I don't believe that was provided in the 15 data. 16 Q. Does it include whether or not this is a CNS 17 active medication that would either accelerate the actions of 18 the antidepressant under study or decelerate the actions or 19 sedate the actions? 20 A. There are a large number of different types of 21 medications, some of which I know are CNS active and some of 22 which I don't know. They were just a lot of different 23 medications. 24 Q. Does this give you concern about the Prozac 25 clinical trials? 115 1 A. This would seem to muddy the waters considerably 2 in terms of drawing conclusions about the data, about the 3 effects of Prozac, imipramine and placebo, because there are 4 other indeterminate effects of these medications, as well as 5 possible interactions with the psychoactive antidepressants. 6 Q. If you were designing a trial, would you have 7 any concomitant medications? 8 A. No. 9 Q. Why? 10 A. Because you would lose the ability to determine 11 what an effect was due to, and in this particular case you 12 could look at it the other way. You may have an effect in 13 here, but the concomitant medication is ameliorating that 14 effect and canceling it out. It can go at either direction. 15 But at the simplest level, you simply don't have the ability 16 to draw strong conclusions about the effect of your 17 manipulation if you have thrown in here another variable or 18 other medications. 19 Q. Let me ask you this, Doctor Brown. In all the 20 testing that you've done, all the research design that you've 21 done, and every time that you've applied a statistical 22 principle, have you ever massaged data? 23 A. No. 24 Q. Is massaging data some proper statistical 25 procedure? 116 1 A. In psychology it has a distinctly negative 2 connotation. 3 Q. Why? 4 A. The connotation is that you look at the 5 individual subjects and you keep the ones that support your 6 theory and you throw the ones out that don't, find some 7 justification for throwing out odd data points. That's one 8 way of massaging. Another way is to continue to run 9 statistical tests on the data until one turns out to be 10 significant. 11 Q. Is that good or bad? 12 A. Well, that's bad because you're going to find a 13 statistical test significant inappropriately 1 time out of 20 14 if you use a significance level of .05. 15 Q. All right. 16 A. So we also call that fishing. 17 Q. What? 18 A. Fishing. A fishing expedition. And that's also 19 inappropriate. 20 Q. But you've not seen the term "massaging data" 21 used in a beneficial way? 22 A. No. 23 Q. In all your years? 24 A. No. 25 Q. How about cap? We've seen a document that says 117 1 that Doctor Leber was indicating that there should be to 2 Doctor Leigh Thompson a cap on the number of events. Does 3 that have any particular statistical nomenclature, cap? 4 A. I'm not familiar with that specifically. I 5 would interpret it to be that you collect data until you have 6 the conclusion that you need and then stop collecting data, 7 but that's strictly my conjecture. I'm not that familiar with 8 that term. 9 Q. Would cap in statistics mean the same thing as 10 cap as we ordinary people say when we say put a cap, put a 11 limit on it? 12 A. I would assume that's the case. 13 Q. Cap is not defined in any statistical dictionary 14 that you've ever seen? 15 A. Not that I'm aware of. 16 Q. Is massage defined in any statistical dictionary 17 you've seen, Doctor Brown? 18 A. I don't recall ever seeing that. 19 MR. SMITH: I'm at an area, Your Honor, where I 20 can break. 21 JUDGE POTTER: Okay. We'll go ahead and take 22 the lunch recess at this time. Ladies and gentlemen, I'm 23 going to remind you again of my admonition. Don't allow 24 anybody to communicate with you about this case or any topic 25 connected with this case; do not discuss it among yourselves 118 1 or do not form or express opinions about it. I think I cut 2 ten minutes off your lunch hour yesterday, I'll give you ten 3 minutes. We'll stand in recess till 2:00. 4 (JURORS EXCUSED FOR LUNCH RECESS; 5 HEARING IN CHAMBERS) 6 JUDGE POTTER: We're talking about the 7 deposition of Doctor John Heiligenstein, April 27th, 1994. 8 Ms. Zettler has designated certain things to be read. The 9 Defendant has objections and, really, they're more primarily 10 things needed to be added to complete the deposition. And 11 we're going through these objections made by -- signed by Mr. 12 Myers on October 25th. 13 MR. MYERS: This morning. 14 JUDGE POTTER: And Ms. Zettler has gone through 15 them as an initial proposition, and 13 through 22 are fine 16 with her. We need to take up 23 through 24. 17 MR. MYERS: That goes through 25, I think, 18 doesn't it? 19 JUDGE POTTER: Yes, sir. 20 MS. ZETTLER: The black stuff is the stuff that 21 there's no contest on; the purple is what they want. Just 22 another color change. Pen ran out. I've gone through a lot 23 of highlighters in this case. 24 JUDGE POTTER: Why is not 23 through 24 blue? 25 MS. ZETTLER: Can I tell you what my problem is 119 1 with that, Judge, real quickly? All of these pages before 2 this are -- 13 through 22 go directly to his qualifications. 3 We've allowed them to qualify the heck out of him. All this 4 section is symposiums he's attended. We don't want it in, 5 one, for the sake of brevity and, two, for the sake of 6 relevance purposes. We've really let them just go nuts with 7 this guy and put in all his appointments at hospitals and his 8 board certification and his term with the army when he worked 9 at Fort Sheridan up in Chicago as a pediatric psychiatrist, et 10 cetera, et cetera, et cetera, his chairmanship of the 11 department at Lutheran General Hospital outside Chicago. It's 12 going to be a real long-read deposition, Judge. We've tried 13 to cut it down as much as we can. 14 JUDGE POTTER: Maybe I'll change my mind after 15 you get to me, if I get down in here further and decide. But 16 right now I'm going to let them put in his qualifications. So 17 that is sustained, 23 through 24. 18 MS. ZETTLER: 26 I've added in. 19 MR. MYERS: What about 27? 20 MS. ZETTLER: 1 through 10 on 27. The rest of 21 it is -- let me take that back. We said okay on the rest of 22 this stuff, and if they want it we want the rest of the page 23 in. 24 JUDGE POTTER: You gave them 26 down to... 25 MS. ZETTLER: 10. Or down to 15, actually. 120 1 MR. MYERS: On 27? 2 MS. ZETTLER: Right. 3 JUDGE POTTER: So she's saying on 27 she will 4 read down to Line 15, the whole thing comes in. 5 MR. MYERS: That's fine on 26 and 27, but I 6 still want what's on 28. 7 MS. ZETTLER: 28 is okay. 8 MR. MYERS: Okay. I'm sorry. 9 MS. ZETTLER: 28 through Line 19 is already in, 10 Judge, on 28. 11 JUDGE POTTER: This is already in? 12 MS. ZETTLER: He's already agreed that this can 13 come in. 14 MR. MYERS: I've agreed that 14 through 19 can 15 come out on Page 27, and she's going to read 9 through 19, as 16 I understand it, 6 through 19. 17 MS. ZETTLER: Right. 18 JUDGE POTTER: All right. 30 and 31. 19 MS. ZETTLER: 1 through 3 is fine with us; the 20 rest we think is irrelevant. We're talking about 1 patient. 21 It goes to your order about causality in 1 patient. 22 MR. MYERS: I'll withdraw 30 and 31. 23 JUDGE POTTER: Okay. Now, you're sure that one 24 got picked up? 25 MS. ZETTLER: Yeah. This is what I've been 121 1 doing, so we'll just use the thick black lines. 2 JUDGE POTTER: All right. 3 MS. ZETTLER: That's just another... 4 JUDGE POTTER: It's really a downplaying of his 5 qualifications. 6 MS. ZETTLER: Okay. We'll take it. 7 JUDGE POTTER: We'll let it in. 37 comes in. 8 He has 1 through 18; I think it's really 3 through 18. 9 MR. MYERS: 4. 10 JUDGE POTTER: All right. 4 through 18. 11 No. 40. 12 MR. MYERS: This actually goes 40, 41, 42 13 and 43. 14 JUDGE POTTER: This is more puffing? 15 MS. ZETTLER: Yes. Plus, Judge, it kind of ties 16 into another objection that we have to some of the testimony 17 they're going to read. Some of this has to do with an 18 agitation study that was done. We didn't get into the 19 agitation issue at all on this deposition. They're bringing 20 in Doctor Tollefson, who was the head person at Lilly that was 21 involved in this. 22 MR. MYERS: Doctor Lord testified about it 23 yesterday at 3:10 P.M. I wrote it down. 24 MS. ZETTLER: Doctor Tollefson is coming here 25 live; they've already said that. He is the guy that is the 122 1 head guy at Lilly on the study. 2 MR. MYERS: But this doctor was the monitor 3 because when Tollefson was on the study he was outside Lilly. 4 MS. ZETTLER: I'm talking about two different 5 papers, Larry. We get into this aggression article ad nauseum 6 on this, too. 7 JUDGE POTTER: This is how he's written about 8 Prozac, so 40 through 43 is sustained. I can't read your 9 handwriting here. 10 MS. ZETTLER: To Tollefson coming. Actually, I 11 think this entire black is about that agitation, down through 12 53 or 54. 13 JUDGE POTTER: 45. Let's look at 45. Does this 14 study come up anyplace else in your examination, Ms. Zettler? 15 MS. ZETTLER: No. In fact, we specifically, to 16 shorten this up, kept it out. 17 JUDGE POTTER: What I'm going to do then is if 18 you want to go back and read it as part of, you know, like 19 cross-examination, you can. How far down does it go, this 20 block? 21 MR. MYERS: To 48. 22 MS. ZETTLER: No. I think it goes all the way 23 through 54, Judge, if you look. 24 JUDGE POTTER: Well, it looks like it. 25 MS. ZETTLER: I believe it goes all the way 123 1 through 54. 2 JUDGE POTTER: Yeah, it does. 3 MS. ZETTLER: Can I make a couple other points 4 here, Judge? This is a study that was not completed at the 5 time that we took these depositions. We have never seen 6 anything except for what has been published in the literature 7 as far as whether or not concomitants were used. The 8 information that we do have was from Doctor Tollefson and 9 Doctor Greist, one of their experts, who was also a clinical 10 investigator on this trial. This study is going to be talked 11 about ad nauseum. I don't think it's necessary to do anything 12 with this witness on it, especially since they're not going to 13 bring this guy in live. 14 JUDGE POTTER: If they want to read it on cross, 15 they can. Have you gotten the study? 16 MS. ZETTLER: We've not gotten anything on the 17 study, even though we've asked for it. 18 JUDGE POTTER: But you've got it now? 19 MS. ZETTLER: Right. But we didn't have it at 20 the time we talked to this guy. 21 JUDGE POTTER: But you've got it now, and when 22 the head guy comes in you've got it. 23 MS. ZETTLER: All we have is the published 24 report. 25 JUDGE POTTER: You can do the best you can with 124 1 that. It may be a little late to be doing more discovery. 2 79, 80, 81, 82, 83, are we still on the... 3 MS. ZETTLER: Yeah. 4 MR. MYERS: No. Actually, it stops at Page 80, 5 the discussion about the study, on about Line 16 or at 20, 6 somewhere between there is where they stop talking about the 7 study on Page 80. 8 JUDGE POTTER: What is your thrust of this? So 9 what we're talking about -- 10 MR. MYERS: The question about the study stops 11 it looks like the question on -- 12 JUDGE POTTER: We'll start with -- but you say 13 in this trial and then they switch over. Let's see. 14 MS. ZETTLER: Here he's talking about during the 15 placebo washout phase of the trial. 16 MR. MYERS: It really stops at Line 19. 17 MS. ZETTLER: But we were talking about suicidal 18 ideation that happens in the trial. 19 MR. MYERS: I didn't ask the questions; I was 20 just there. 21 JUDGE POTTER: Okay. I'm going to do the same 22 thing. Where does this series run through, 83? 23 MR. MYERS: Yes, sir. 24 JUDGE POTTER: Okay. So 80 through 83, and I 25 guess 79, what did we do with 79? 125 1 MR. MYERS: 79 up to through 19 on Page 80 deal 2 with the trial. 3 JUDGE POTTER: All of that could be read as if 4 on cross-examination. 5 MS. ZETTLER: Then we request that the last 6 question starting at the bottom of Page 83 be included in 7 that. 8 MR. MYERS: I'm sorry? 9 MS. ZETTLER: The last question on 83 and the 10 first question on 84. 11 JUDGE POTTER: Then if you read it you have to 12 add 83 through Line 24 on this page and 84 through Line 1. 13 MR. MYERS: Line 1. So as I understand it, 79 14 through Line 19 on Page 80 are out, and I can read those if I 15 want, but they are to read -- 16 JUDGE POTTER: No. No. All of it. 17 MS. ZETTLER: If you want it, you have to read 18 it. 19 JUDGE POTTER: All of it from Page 45 to 20 83, if you want to read it you have to do it on cross. 21 MR. MYERS: It's a different subject matter. 22 JUDGE POTTER: It's a different subject, but I'm 23 taking it for both of them. 24 MS. ZETTLER: 106 is fine. 25 JUDGE POTTER: 110? 126 1 MS. ZETTLER: That's an objection. 2 JUDGE POTTER: A real objection. Is ELECT the 3 right word? 4 MS. ZETTLER: Yeah. There's ELECT dictionary 5 and COSTART. They wanted that and I put that in. 6 MR. MYERS: What's that? 7 MS. ZETTLER: The 106 stuff. 8 MR. MYERS: Oh, right. 9 JUDGE POTTER: Okay. I don't understand the 10 objection, but if the objection -- you're going to win it -- 11 if the objection is just to Lines 5 through 14. 12 MR. MYERS: Right. I don't care about the 13 question on Line 15. 14 JUDGE POTTER: We've got a question by Ms. 15 Zettler and an answer by Mr. Myers and a comment by Ms. 16 Zettler. 17 MS. ZETTLER: No. Because it doesn't make 18 sense. Why don't we leave this in and take this out. That 19 makes it clearer, because this is going to come out of 20 nowhere, Judge. Leave the first question in. 21 MR. MYERS: The reason you make a formal 22 objection is so you can cure it at the time. We made the 23 objection and they didn't change the question. 24 MS. ZETTLER: Yes. I said "related." 25 JUDGE POTTER: Okay. I'm going to stick with my 127 1 ruling and sustain this objection. 2 134 and 135. Mr. Myers, she gave you 114, 117 3 and 118. 4 MS. ZETTLER: But the rest of this stays in; 5 right? 6 JUDGE POTTER: Right. 7 MS. ZETTLER: It's going to be real confusing. 8 JUDGE POTTER: 134, 135. 9 MS. ZETTLER: We start all over again at 135 in 10 the same question. 11 JUDGE POTTER: Now, this is something, Ms. 12 Zettler, he did during the deposition or is this something 13 they did a long time ago? 14 MR. MYERS: This is a continued explanation. 15 Most of the first day was taken up with him explaining how 16 they did this paper and what the methodology was. 17 JUDGE POTTER: So this is talking about a paper 18 that he did? 19 MR. MYERS: Most of what they're reading from 20 about Page 90 to 100. 21 JUDGE POTTER: So when they are saying where you 22 had taken the 1639s, they're talking about at another time, 23 not during the deposition? 24 MS. ZETTLER: Right. Right. 25 MR. MYERS: Right. 128 1 JUDGE POTTER: Okay. Well, unfortunately, 2 though, to understand the Xs and the Ys, I think you did what 3 you said, but to understand what an X and a Y is, you've got 4 to put the false starts in, so I'm going to put in 134 and 5 135. 6 141. I don't understand on 141 too much whether 7 it's in or out. What's the objection to it, Ms. Zettler? 8 MS. ZETTLER: He wants this in. 9 JUDGE POTTER: I know. What's your objection to 10 that? 11 MS. ZETTLER: What my objection to it is, it's 12 self serving. 13 JUDGE POTTER: We went over this, self serving 14 is not an objection. 15 MS. ZETTLER: How about nonresponsive? 16 JUDGE POTTER: That might get it. Does 141 give 17 us about an hour? 18 MS. ZETTLER: It should. 19 JUDGE POTTER: Is there a place you want to 20 break this afternoon? Why don't you look and see if there's a 21 place you want to break. 22 MS. ZETTLER: Why don't we do it by Exhibit 4. 23 We could go ahead and just finish this, Judge. I think a lot 24 of it can be stuff they can pull and read themselves because 25 it's big chunks of unrelated things. 129 1 MR. MYERS: Yeah. And I'd like to be heard on 2 some of this other stuff. 3 MS. ZETTLER: 147 is in, Larry. I've agreed to 4 that. So let's do this. 5 JUDGE POTTER: 153 is the next one. 6 MS. ZETTLER: This could probably work up to 7 151. 8 MR. MYERS: 153 is where we need to start our 9 next discussion? 10 MS. ZETTLER: Let me ask you this. The stuff 11 that you're going to have them pull, they have to read it at 12 the end of the entire deposition? 13 JUDGE POTTER: Right. 14 MS. ZETTLER: We may be going shorter than I 15 originally anticipated. It should put it until after four. 16 JUDGE POTTER: That's fine. 17 (HEARING IN CHAMBERS CONCLUDED; LUNCH RECESS) 18 JUDGE POTTER: Mr. Smith, I assume you want 184 19 in? 20 MR. SMITH: Yes. Did I hand it out? 21 JUDGE POTTER: 184 is admitted. 22 (BENCH DISCUSSION) 23 MR. MYERS: I just want to ask the Court and 24 Mr. Smith when I examine the Witness I may use those boards he 25 has that have the plastic on them, and I have a dry marker 130 1 that erases; I just want you to know that that erases. 2 JUDGE POTTER: Okay. 3 MR. SMITH: I'm not picky like Mr. Stopher is. 4 I'm not going to be like Mr. Stopher and be picky about my 5 exhibits. 6 MR. STOPHER: That microphone does not work over 7 here. 8 (BENCH DISCUSSION CONCLUDED) 9 SHERIFF CECIL: The jury is now entering. All 10 rise. All jurors are present. Court is back in session. 11 JUDGE POTTER: Please be seated. Doctor, I 12 remind you you're still under oath. 13 Mr. Smith. 14 Q. Doctor Brown, as I understand it, you reviewed 15 some of the protocols in connection with the Prozac clinical 16 trials; is that correct? 17 A. Correct. 18 Q. Several of those protocols -- I think probably 19 all of the protocols had what's called a placebo washout 20 period. Did you notice that in your review of the protocols? 21 A. Yes. 22 Q. Do you have any criticism of the use of a 23 placebo washout period or do you have any opinions concerning 24 whether or not that would affect the predictability of the 25 clinical trials in actual trial population of the depressed 131 1 people as a whole? 2 A. In reviewing the data on the placebo washout, I 3 have two concerns with that particular technique. One of the 4 concerns is a general one about throwing out more subjects, to 5 use the term loosely. What you're doing is at the beginning 6 of the investigation you have all subjects take one week on 7 the placebo and anybody who responds positively to that 8 placebo within a certain guideline you throw out, you exclude 9 them from the main study. And the purpose of this is to 10 exclude people who are simply responding to a sugar pill 11 effect, that is, they're responding to an inert substance, a 12 psychoactive inert substance. In psychological research, the 13 purpose of the placebo group to begin with is to catch that 14 type of response, change, and use that as a baseline. We 15 don't throw out those people, we include them in the studies. 16 So you have another -- still another 17 exclusionary criteria with the research project. So you have 18 tossed out people who are seriously suicidal, people who have 19 had difficulties with drugs or alcohol within one year prior 20 to the study, and you're now excluding people who for whatever 21 reason are responding positively to a placebo. So you're 22 progressively narrowing or thinning the group of individuals 23 to whom you can apply the outcome of the study. 24 Besides the general objection to the placebo 25 washout, I have a more specific concern, and that came about 132 1 in reading another article about the Prozac tests. In an 2 article that I read, there was an indication that over 80 3 percent of the individuals who were evaluated in this type of 4 research were on an antidepressant medication prior to the 5 study, and they were removed just immediately before the 6 placebo washout phase for the Prozac research. 7 Q. Let me understand you, Doctor Brown. Are you 8 saying that these are people who had been treated for their 9 depression previously by use of other antidepressant 10 medications? 11 A. Yes. 12 Q. All right. Go ahead. 13 A. As you may know at this point, a lot of the 14 antidepressants do have side effects of various sorts and 15 these side effects can be moderately negative. My concern is, 16 as a researcher in general, is that if you stop the 17 antidepressant that they're on, give them a one-week period in 18 which to respond to a placebo, the people that are getting 19 better on that placebo may not be responding to the placebo, 20 they're responding to the fact that they're now off of the 21 prior medication, which had side effects, and in that certain 22 period of time they may feel an elevation of mood or a 23 reduction in depression simply because they have those other 24 secondary side effects reduced. Now, this may not continue on 25 for a period of time, but my concern is that that clouds the 133 1 issue even more, that you're excluding people not because 2 they're responding to a sugar pill, so to speak, you're 3 excluding people because they're being withdrawn from a prior 4 medication and they're experiencing the alleviation -- 5 temporary alleviation of the side effects of the other 6 medication. 7 Q. Have you done any clinical trials for 8 pharmaceutical companies, Doctor Brown? 9 A. No. 10 Q. Do you regularly, though, engage in testing 11 where you design studies to measure responses of individuals? 12 A. Yes. 13 Q. Should the same principles apply if you're 14 attempting to measure psychological responses? 15 A. Yes. 16 Q. Why is that? 17 A. All the difficulties that I've brought up to 18 this point make it difficult or impossible to interpret the 19 outcome of research or generalize it appropriately. And it 20 really doesn't make any difference whether you're testing as 21 your variable types of drugs or you're testing different types 22 of learning materials or different types of social situations 23 in research. If you're manipulating a variable, the standards 24 for that manipulation should be the same in order to get 25 clean, quality data that you can generalize appropriately back 134 1 to the group that you're seeking to apply it to. 2 Q. Did you have an opportunity to review any 3 material in connection with the material that was supplied to 4 the Food and Drug Administration by the Food and Drug 5 Administration concerning adverse events? 6 A. You're speaking of -- 7 Q. Postmarketing data? 8 A. -- the spontaneous domestic reports? 9 Q. Yes. 10 A. Yes, I had a chance to look at those. 11 Q. Previously we have introduced a group of 12 material, I believe it's Plaintiffs' Exhibit 120. Do you have 13 it in front of you, Doctor Brown? It was Exhibit 9 to your 14 deposition. 15 A. I don't have that in front of me, but I do have 16 that. 17 Q. All right. 18 Your Honor, I have some other copies of 19 Plaintiffs' Exhibit 120, which we marked as 186 for the jury's 20 consideration in case they left them. 21 JUDGE POTTER: So what you're giving is -- 186 22 is a duplicate of what's already in as one -- what is it in 23 as? 24 MR. SMITH: 120. 25 JUDGE POTTER: Are you sure about that other 135 1 number? 2 MR. SMITH: We'll check the original, Your 3 Honor. 4 JUDGE POTTER: Okay. I just am looking at the 5 summary you-all gave me. 6 MR. SMITH: Actually, Your Honor, 120 has the 7 note in front of it. 8 JUDGE POTTER: All right. Okay. Why don't you 9 give them to my sheriff and she'll pass them out and then 10 collect them up. 11 SHERIFF CECIL: (Hands document to jurors). 12 Q. Did you review this material, Doctor Brown, to 13 form opinions or conclusions in connection with the Prozac 14 clinical trials? 15 A. Yes. 16 Q. Can you in a capsule tell us what this set of 17 material added to or did in connection with an analysis of 18 your opinion? 19 A. It enhanced my skepticism of the veracity of the 20 research undertaken and sponsored by Lilly in terms of the 21 effects of Prozac. 22 Q. Why was this significant to you? Why was the 23 postmarketing event significant? 24 A. There seemed to be -- there seemed to be a 25 dramatically different story in terms of the difference 136 1 between Prozac and comparitor drugs with respect to different 2 types of hostile aggressive acts. 3 Q. Would this be a larger or smaller group of 4 individuals than that group as defined by the Prozac clinical 5 trials? 6 A. Theoretically, it would encompass a larger 7 group. 8 Q. Because this is all individuals reflective of 9 the experience of the drug once it's marketed to the general 10 public? 11 A. Yes. 12 MR. MYERS: Your Honor, could Mr. Smith ask some 13 direct questions? 14 JUDGE POTTER: Okay. It's leading, Mr. Smith. 15 Q. Turn with me to Page PZ and the last four 16 numbers are 1903. Do you see that? 17 A. Yes. 18 Q. What is the heading of that? 19 A. Would you like me to read that? 20 Q. Yeah. 21 A. "Spontaneous Domestic Reports received January 22 1982 to July 1991." 23 Q. And is there various medications listed there? 24 A. Yes. 25 Q. And are you familiar with the other drugs in 137 1 addition to fluoxetine? 2 A. In what sense? 3 Q. In knowing generally whether they're other 4 antidepressants or not? 5 A. I believe they are. 6 Q. There is some handwriting on this page. Whose 7 handwriting is that? 8 A. That's mine. 9 Q. And there are numbers out to the right; what are 10 those numbers out to the right? 11 A. Those are the totals for each row. 12 Q. All right. So you've just added up the three 13 columns, suicide attempts, overdose and psychotic 14 depression -- 15 A. Yes. 16 Q. -- in each category and then you have graphed 17 them out? 18 A. Yes. 19 Q. Grafted them out? 20 A. Yes. 21 Q. And can you identify Exhibit 187, Doctor Brown? 22 A. Yes. This is a graphical representation of the 23 numbers on Exhibit 1903, or on Page 1903. 24 MR. SMITH: We would offer Exhibit 187, Your 25 Honor. 138 1 JUDGE POTTER: Be admitted. 2 SHERIFF CECIL: (Hands document to jurors). 3 Q. Okay. So we can understand, is this exhibit 4 simply a graphic representation of Page 1903? 5 A. Yes. 6 Q. And this has to do with suicidality; is that 7 correct? 8 A. As well as psychotic depression and propensity 9 to overdose. 10 Q. All right. You may not know that Lilly has 11 classified these three things in a similar category as 12 suicidality. 13 A. I did not know that. 14 Q. Anything of significance to you, Doctor Brown, 15 in the figures we see here? 16 A. There seems to be a rather dramatic difference 17 between Prozac and the other groups, other antidepressants in 18 terms of the frequency of reports. 19 Q. Is it your understanding this is raw numbers? 20 A. Yes. This is raw numbers. It's not adjusted by 21 the number of prescriptions, number of individuals taking the 22 medication. 23 Q. This has the year 1982 to July 1991; is that 24 correct? 25 A. Yes. 139 1 Q. Did you know that Prozac only came on the market 2 basically the first of the year 1988? 3 A. Yes. 4 Q. And that these other antidepressants had been 5 existing since 1982? 6 A. I did not know that. 7 Q. Is that of significance that you're looking at 8 figures where these other antidepressants have in effect a 9 five-year head start, six-year head start? 10 A. It's remarkable, but still it needs to be 11 buffered by the number of prescriptions. It's still very 12 suspicious data, I'll put it that way. 13 Q. All right. Well, if you turn to Page PZ 1905, 14 would that give you some better insight, since that is 15 reflected in percentage of reports? 16 A. As I understand the way that's computed, that is 17 a fair comparison since they are adjusted for prescriptions 18 for doses. 19 Q. Did you graph that out? 20 A. I believe -- is that a graph of the suicide 21 reports? I don't think that is. 22 A. No. No. That's not a graph of this page. 23 Q. Look at Page 1905. Since we don't have that 24 graph out, is there a difference there to you in the 25 percentage of total reports between Prozac and these other 140 1 drugs? 2 A. At least with respect to suicide attempts, it 3 does appear to be a meaningful difference. 4 Q. All right. How about overdose? 5 A. No. 6 Q. How about psychotic depression? 7 A. It's less of a difference. I would be less 8 confident that that's a significant difference, but certainly 9 it is; it still corroborates the suicide difference. 10 Q. All right. If we turn to Page 1911, would that 11 give us suicide attempt, overdose and psychotic depression in 12 reports per million compared to fluoxetine? 13 A. I'm sorry. Could you restate the question? 14 Q. 1911, is that better reflective of the true 15 incidence of this reporting? 16 A. That's also adjusted prescriptions, yes. 17 Q. All right. Let me hold a blowup of that up and 18 ask you to explain that to us, Doctor Brown. This appears to 19 be adjusted on reports per million and there's a comparitor 20 drug of Trazodone. 21 A. This apparently indicates the total number of 22 reports per million prescriptions written and plotted on a 23 year-to-year basis since 1982, and it indicates that the 24 number of reports per million is quite a bit higher for Prozac 25 than it is for the comparitor drug. 141 1 Q. Have you performed a statistical analysis to 2 determine whether or not that is a statistical significant 3 difference in 1988, '89, '90 and up to '91? 4 A. I have not done that, but I can bet the farm 5 that there would be a difference for those years even without 6 performing the test. 7 Q. Even we statisticians -- it doesn't take a 8 statistician to see the significant difference in the numbers? 9 A. Correct. 10 Q. When it's graphed out like this? 11 A. Correct. 12 Q. Again, we have no black marks for Prozac from 13 '82 to '87. 14 A. Yes. 15 Q. The reason being? 16 A. It wasn't introduced. 17 Q. What does that tell you about the design and 18 implementation of the Prozac clinical trials, Doctor Brown? 19 A. It confirms my discomfort with those as an 20 accurate indication of the side effects of Prozac. 21 Q. You mean your discomfort with the Prozac 22 clinical trials? 23 A. Yes. Yes. I'm suspicious of the research done 24 on a number of different bases and the fact that the research 25 found no difference -- consistently no difference between 142 1 Prozac and comparitor drugs, and this suggestion that maybe 2 there is something out there that should be examined more 3 carefully with better research. 4 Q. Let's talk about hostility. There's data in 5 this package on spontaneous reports on hostility, is there 6 not? 7 A. Yes. 8 Q. If we turn to Page 1904 -- well, let's turn to 9 190 -- well, if we turn to Page 1904, do you see a difference 10 in reports of hostility and intentional injury between Prozac 11 and these other antidepressants? 12 A. Yes. 13 Q. Is that of significance to you? 14 A. Well, yes, but it's limited because it's not 15 adjusted for number of prescriptions. 16 Q. Well, would it be helpful like on Page 1906 if 17 you compared reports of hostility and intentional injury as is 18 done here? 19 A. Yes. That's helpful. 20 Q. Because that's a percentage of total reports 21 attributable to these two things; is that right? 22 A. Correct. 23 Q. And have you graphed that out for us, Doctor 24 Brown? 25 A. I believe so. 143 1 Q. It is Exhibit 188, the graph that you've done? 2 A. Yes. 3 Q. We would offer 188, Your Honor. 4 JUDGE POTTER: Be admitted. 5 SHERIFF CECIL: (Hands document to jurors). 6 Q. Now, is what you've done on 188, Doctor Brown, 7 comparable to what the jury has in their hands as 1906? 8 A. It's a modification of that data. What I've 9 done is collapsed the four other antidepressants and done an 10 average across the other four and called it Others, and I've 11 done that for both hostility and intentional injury and 12 compared that with the fluoxetine percents. 13 Q. What does that tell you? 14 A. Well, it appears that this particular data which 15 is adjusted by the total reports, the percent of complaints 16 that -- or problems, difficulties that involve hostility is 17 considerably greater with Prozac than with the other drugs, 18 and this is also true with intentional injury. The percent of 19 all complaints which involve intentional injury with Prozac is 20 considerably higher than the percent of all complaints that 21 involved intentional injury with the other antidepressants. 22 Q. It's the average of the other antidepressants? 23 A. It is the average of all the other 24 antidepressants. 25 Q. Are these statistically significant, those 144 1 numbers? 2 A. I did not test that. 3 Q. Do they appear to be statistically significant? 4 A. For sure on the intentional injury I could say 5 with some surety that that would be a significant difference. 6 Q. In other words, not just happening by chance 7 when you say it's statistically significant? 8 A. It seems like that would be likely that that 9 would turn out that way. 10 Q. Not by chance? 11 A. Not by chance. 12 Q. Would it be helpful to see the actual percentage 13 adjusted or the actual number adjusted to reports per million 14 on hostility, Doctor Brown? 15 A. That would also -- yes. Yes. 16 Q. If we look at Exhibit 19 -- or if we look at on 17 this pack of exhibits PZ No. 1912, what does that show you? 18 A. That gives the same impression, except from a 19 slightly different perspective because there's only one 20 comparitor antidepressant and it's per million prescriptions 21 rather than per percent of reports. 22 Q. Is that significant to you? 23 A. It certainly appears that the Prozac reports are 24 considerably higher than the comparitor. 25 Q. Trazodone -- 145 1 A. Correct. 2 Q. -- is the comparitor? Can you see or look at 3 that, can you see the different -- is this adjusted per 4 million prescriptions? 5 A. Yes. 6 Q. What is the reason for doing that, adjusting it 7 to per million prescriptions? 8 A. That's to accommodate the fact that more people 9 take one drug than the other. That adjusts for -- that 10 essentially equates the data for total number of 11 prescriptions. 12 Q. And do you see these differences in 1988 between 13 Prozac and Trazodone on hostility and intentional injury? 14 A. Yes. 15 Q. Does that appear to be statistically 16 significant? 17 A. I would say that would be for sure. 18 Q. How about 1989? 19 A. Yes. 20 Q. How about 1990? 21 A. Apparently. 22 Q. How about the first seven months of 1991? 23 A. Appears to be. 24 Q. That is, that these differences would not just 25 occur by chance? 146 1 A. No. 2 Q. What does this tell you about what you saw in 3 the clinical trials? 4 A. Again, it makes me suspicious that the tests 5 were inadequate in some way. If there's such a large 6 discrepancy between the outcome of the clinical studies and 7 the reports from the public, that maybe those research studies 8 were not designed properly to address the question of whether 9 there's a difference between Prozac and other antidepressants 10 with respect to different forms of hostile and aggressive 11 behavior, self-injurious behavior. 12 Q. As an individual that spent the last 20 years in 13 designing, implementing and conducting experiments, do you 14 have an opinion as to whether or not that Prozac clinical 15 trials were adequately designed and implemented? 16 A. My opinion is that they were not. 17 Q. That's all we have, Your Honor. 18 JUDGE POTTER: Mr. Myers. 19 MR. MYERS: Thank you. 20 21 EXAMINATION ___________ 22 23 BY_MR._MYERS: __ ___ ______ 24 Q. Professor Brown, you are from Dallas, Texas; 25 correct? 147 1 A. I reside there. 2 Q. Yes, sir. And that's where Mr. Smith is from; 3 correct? 4 A. Yes, sir. 5 Q. And do I recollect that from your deposition you 6 told us that your wife and Mr. Smith's wife were social 7 acquaintances of some kind? 8 A. Yes. 9 Q. You knew him in that capacity before you became 10 involved in this case; correct? 11 A. No. 12 Q. Your wife knew his wife? 13 A. Right. 14 Q. All right, sir. Now, you are a psychologist by 15 profession; correct? 16 A. Yes. 17 Q. Your area of training is in something called 18 experimental psychology; correct? 19 A. Yes. 20 Q. And your field -- and I think you've explained 21 it earlier -- is something called memory and cognitive 22 processes; correct? 23 A. Yes. 24 Q. All of your degrees, your Bachelor's and your 25 Master's and your Ph.D. are in psychology; correct? 148 1 A. Yes. 2 Q. You do not have any degree in statistics; 3 correct? 4 A. Correct. 5 Q. You do not have any degree in biostatistics, do 6 you? 7 A. No. 8 Q. As I understand it, when you were in graduate 9 school at Northwestern you took some statistical courses, but 10 those were taught within the department of psychology; isn't 11 that right? 12 A. Correct. 13 Q. You did not take those courses in the statistics 14 department, did you? 15 A. No. 16 Q. And would the same be true for those statistical 17 courses that you took in undergraduate school, that those were 18 taught within the department of psychology? 19 A. Correct. 20 Q. You are not a biostatistician, are you, sir? 21 A. No. 22 Q. And you're not a statistician within the formal 23 meaning of the word, are you? 24 A. As a profession, I'm not a statistician. 25 Q. All right. In terms of your teaching, do I 149 1 understand that you have taught three statistical courses? 2 A. Three different statistical courses. 3 Q. Three different statistical courses. And that 4 has been over the time that you've been at SMU; correct? 5 A. Yes. 6 Q. And am I correct -- and I think you told this in 7 your deposition -- that you've not taught one of those courses 8 for about three or four years; is that right? 9 A. That's correct. 10 Q. And another one of the courses you've not taught 11 for about ten years; isn't that correct? 12 A. That's correct. 13 Q. In the research work that you do, do you use a 14 computer to crunch and run the numbers from your studies? 15 A. You bet. 16 Q. And as I understand it, you use a software 17 package for your statistical work called SPSS, which is the 18 Statistical Package for the Social Sciences; correct? 19 A. Correct. 20 Q. You don't use a statistical package called SAS, 21 S-A-S, do you, sir? 22 A. Others in our department do, but I don't. 23 Q. That's a package that's used more for the 24 medical and physical sciences, isn't it? 25 A. Correct. 150 1 Q. And is it your understanding that that was in 2 fact the software that was used to run a number of the Lilly 3 analyses? 4 A. I believe I've been told that. 5 Q. All right. There is a statistics department, is 6 there not, at SMU? 7 A. Yes. 8 Q. But you don't teach there, do you? 9 A. No. 10 Q. I know you've expressed to the jury some of the 11 concern about the teaching ability of some of their statistics 12 teachers, at least their communications skills, but isn't it 13 correct that the statistics courses in the statistics 14 department are more technical in nature than those taught in 15 your department? 16 A. Yes. 17 Q. Do you subscribe to or read any of the 18 professional statistical journals? 19 A. No. 20 Q. And you've not published in any of them, have 21 you? 22 A. No. 23 Q. You've not studied from a research standpoint 24 the subject of mood disorders, have you, sir? 25 A. No. 151 1 Q. And you certainly don't hold yourself out as an 2 expert in the study or the treatment of mood disorders; 3 correct? 4 A. Correct. 5 Q. Would the same be true for the subject of 6 depression? 7 A. That's true. 8 Q. You have not treated any patients in your 9 career, have you, sir? 10 A. No. 11 Q. There are some psychologists called clinical 12 psychologists that treat patients with various psychological 13 disorders; correct? 14 A. Correct. 15 Q. And, in fact, you have some clinical 16 psychologists in your own department, do you not? 17 A. Yes. 18 Q. But your field and your orientation is different 19 than clinical psychology; correct? 20 A. Correct. 21 Q. Have you ever conducted any professional 22 research into the subject of depression? 23 A. No. 24 Q. And you've never treated a depressed patient; 25 correct? 152 1 A. Correct. 2 Q. Apart from this case, you've never been involved 3 in the design or the application of protocols for 4 pharmaceutical clinical trials; correct? 5 A. Correct. 6 Q. And before getting involved in this particular 7 case, you had never seen a protocol which had been used for a 8 clinical trial on a drug; correct? 9 A. Correct. 10 Q. Before this lawsuit, you had never been asked to 11 review any statistical analyses that had been done for a 12 pharmaceutical clinical trial; correct? 13 A. Yes. 14 Q. Now, earlier, you were talking about the subject 15 of randomization and blinded clinical trials; do you remember 16 that? 17 A. Yes. 18 Q. And you also told the Court and the jury that 19 you had reviewed a number of the clinical trial protocols for 20 Prozac; correct? 21 A. Yes. 22 Q. And you understand, sir, don't you, that those 23 clinical trial protocols, the ones that you reviewed, or at 24 least most of the ones you reviewed, were for blinded clinical 25 trials; correct? 153 1 A. Yes. 2 Q. You have raised certain questions concerning the 3 randomization of the trials, have you not? 4 A. Yes. 5 Q. You're not suggesting that there was an 6 intentional compromise of the blind of the trials, are you? 7 A. I have -- I did not express an opinion as to how 8 the results, the inequity among the groups occurred, but that 9 it was highly unlikely if true randomization were carried out. 10 Q. In your opinion? 11 A. In my opinion. 12 Q. It would be possible under -- even under 13 statistical analysis that the differences that your 14 calculations determined existed was in fact by chance alone; 15 correct? 16 A. That's true. That's always a probability or 17 P level in any statistical analysis. 18 Q. Now, you also talked a little bit about protocol 19 writing and protocol design, and I think you mentioned to Mr. 20 Smith that if a student had submitted one of these Prozac 21 clinical trial protocols that you would have sent it back to 22 them and told them to resubmit it to you in another form; 23 correct? 24 A. I don't remember that. I believe I said that if 25 I submitted data like this to a journal, it would come back. 154 1 But if I said that, then I would admonish the student to 2 straighten out the problems, if this were a hypothetical 3 classroom exercise. 4 Q. Did you know, Professor, that the protocols for 5 the Prozac clinical trials were submitted to the United States 6 Food and Drug Administration -- 7 A. Yes. 8 Q. -- for its review prior to the implementation of 9 the trials? 10 A. Yes. 11 Q. Did you also know that a number of the trials 12 which you reviewed were published, that is, the results of the 13 studies were published in journals? 14 A. Yes. 15 Q. And that those were peer-reviewed psychiatric 16 journals? 17 A. Yes. 18 Q. Now, you went over with Mr. Smith a number of 19 these graphs, and I'd like to take some time and take a look 20 at several of these graphs. Let's start with, so the jury can 21 follow, what has been designated as Plaintiffs' Exhibit 179, 22 and at the bottom of that exhibit it talks about the baseline 23 HAMD-3 mean score. Do you have that there, Professor? 24 A. Yes. 25 Q. You would agree with me, wouldn't you, that -- 155 1 let me stop there. You prepared these graphs; correct? 2 A. Correct. 3 Q. And you would agree with me that in preparing 4 graphs or charts that depict data and numbers, there are a 5 number of different ways to do it; correct? 6 A. Yes. 7 Q. For example, I suppose you could have made a pie 8 chart of this as one alternative? 9 A. Yes. 10 Q. You also could have made the range of numbers 11 different, you could have stretched it out or compressed it 12 somewhat; correct? 13 A. Yes. 14 Q. And you would agree with me that in depicting 15 data and numbers that it's important to give a reasonable 16 depiction of the differences that you're trying to display on 17 a graph; is that correct? 18 A. Yes. 19 Q. All right. Now, on this graph you show what you 20 have calculated to be 40 studies where the Prozac baseline 21 HD-3 mean score was less than the other -- than other studies; 22 correct? 23 A. Than the other condition, whether that be the 24 comparitor or the placebo. 25 Q. All right. So in 40 studies your calculation 156 1 has determined that it was less; correct? 2 A. When you say calculation, I didn't do any 3 computations, I just counted. 4 Q. So your count indicated that it was less than 5 40; correct? 6 A. Yes. 7 Q. And that going out here to the right side, that 8 this 19 -- it's just shy of the 20 line, that it was equal; 9 correct? 10 A. Yes. 11 Q. And in the other 19, is that correct, the Prozac 12 HAMD score was greater? 13 A. Yes. 14 Q. In fact, if you were to combine those studies 15 where it was equal to 19 and those studies where it was 16 greater than -- and this wipes off, Mr. Smith -- you would 17 have a result where you would have 38 studies where the Prozac 18 score was equal to or greater than the other studies; correct? 19 A. Correct. 20 Q. That's just a different way of depicting the 21 tally or the count that you did; correct? 22 A. It would be inaccurate or misleading because 23 you'd have to add that to the bar on the left, also. 24 Q. But if you added it up, there are 38 studies 25 where the Prozac score is equal to or greater than the other 157 1 condition; correct? 2 A. Yes. And there's also 59 where it's less than 3 or equal to. 4 Q. Let's take a look at another chart, Plaintiffs' 5 Exhibit 180, which was the baseline HAMD of zero. Do you see 6 that? 7 A. Yes. 8 Q. This is a graph where instead of starting your 9 percentages at zero, in this one you've started it at twenty; 10 correct? 11 A. Correct. 12 Q. So the Prozac percentage here I think you told 13 us earlier was 36 percent; correct? 14 A. Yes. 15 Q. And the tricyclic percentage was, what, about 16 22? 17 A. Yes. 18 Q. All right. However, in this graph, you would 19 agree with me that the actual bar, the tricyclic bar is four 20 or five times smaller than the Prozac bar that you've depicted 21 on that graph; correct? 22 A. Correct. 23 Q. In terms of percentage, there's not a four or 24 fivefold difference between the Prozac group and the tricyclic 25 group, is there? 158 1 A. That's true. 2 Q. There's a much smaller percentage than that; 3 correct? 4 A. Correct. It's still significant. 5 Q. In your opinion? 6 A. By a statistical test. 7 Q. In your opinion? 8 A. Yes. 9 Q. Okay. But if you had started at zero, for 10 example, at least the graphic depiction, which the jury was 11 shown, there would not be as much of a difference graphically; 12 correct? 13 A. Visually, yes. 14 Q. Look at Plaintiffs' Exhibit 183, sir, if you 15 would, and that was the baseline HAMD total; correct? 16 A. Yes. 17 Q. Do you have one there that you're looking at? 18 A. Yes. 19 Q. All right. And do I recollect that this graphic 20 depiction is a depiction from one investigator in one study; 21 is that right? 22 A. Correct. 23 Q. These are Doctor Bremner's patients; correct? 24 A. Yes. 25 Q. All right. And I added this up and I think that 159 1 what you have depicted here, since you're charting the number 2 of subjects, is a total of 40 subjects; correct? 3 A. I believe so. So you've depicted a total of 40. 4 Did you know, Professor, that there were in excess of 70 5 patients enrolled in this study? 6 A. No. 7 Q. All right. And if in fact there were 70 8 patients in the study, may actually be 72, your graph has not 9 captured the data on all of the subjects in the study; 10 correct? 11 A. I took this directly from a page that he 12 presented and I took all the subjects off of that page. 13 Q. But if in fact he had 70 patients in the study, 14 you have not captured all of the subjects on that graph? 15 A. If that's true, I have not. 16 MR. SMITH: May we approach the bench, Your 17 Honor? 18 (BENCH DISCUSSION) 19 MR. SMITH: The Defendant has not provided us 20 any data on those 78 subjects with respect to this contract. 21 This is like we were talking about this morning. 22 MR. MYERS: Protocol 27 is a pivotal study. I 23 have a page from the pivotal study which shows the number of 24 patients enrolled in the study. 25 JUDGE POTTER: Is it just the Bremner study 160 1 Protocol 27? 2 MR. MYERS: He's one of the investigators. And 3 we've had witnesses -- 4 MR. SMITH: This is material that we haven't 5 seen. We didn't know there were 78 patients. 6 JUDGE POTTER: I don't think that's grounds to 7 object to his question. 8 MR. SMITH: Let me see it because -- yeah. I'll 9 give it back to you. Where does this come from? See, that's 10 a summary that we haven't seen. 11 MR. MYERS: It was one of the masked protocols 12 that we produced to them. 13 JUDGE POTTER: His question was if it turns out 14 that there were 72 people in the Bremner study then you 15 haven't got them all; the answer is yes. The question is not 16 objectionable. 17 (BENCH DISCUSSION CONCLUDED) 18 Q. The patients that are depicted on this, the 40 19 patients that are depicted, they have been grouped on this 20 graph into four different groups based on their HAMD score; 21 correct? 22 A. Yes. 23 Q. And, as we discussed earlier, you can depict or 24 display data in a number of different ways; correct? 25 A. Yes. 161 1 Q. You could have made some other sort of chart or 2 pie chart or different kind of data, couldn't you? 3 A. Yes. 4 Q. If you were simply splitting the groups in half 5 and graph the patients instead of 30 to 33 a HAMD baseline 6 total of 30 to 37, you would end up with 10 fluoxetine 7 patients and 9 imipramine patients; correct? 8 A. Yes. 9 MR. SMITH: Can you see that, Doctor Brown? 10 A. Yes. 11 MR. SMITH: You're entitled to see it. 12 Q. And if you split it on this other side and you 13 looked at the higher end of the scale and you looked at the 14 patients 38 to 46, you would come up with 10 fluoxetine 15 patients and I think 11 imipramine patients, if I've gotten it 16 right? 17 A. Yes. 18 Q. All right. Is it your understanding, sir, that 19 in order to -- you reviewed the clinical trial protocols; 20 correct? 21 A. Yes. 22 Q. That in order to enroll in a number of these 23 depression studies, the patient had to have a baseline 24 Hamilton Depression Scale score of at least 20? 25 A. Yes. 162 1 Q. So these patients at least on this depiction are 2 somewhat more severely depressed; correct? 3 A. You mean in the entire range? 4 Q. Yes. In the entire range from 30 to 46 are more 5 depressed than the patient at the baseline to get into the 6 study; correct? 7 A. Correct. 8 Q. All right, sir. Take a look, if you would, 9 please, sir, at Plaintiffs' Exhibit 184, which is the 10 concomitant medication graph that you made. Do you have that? 11 A. Yes. 12 Q. Now, did I understand you to say on your direct 13 examination that this depiction was of all concomitant 14 medications that the patients had been on; correct? 15 A. Yes. 16 Q. It was not intended to depict, for example, 17 psychoactive or CNS drugs; correct? 18 A. Correct. 19 Q. It might include everything from aspirin or a 20 Tagamet or an ulcer drug to some heart medication or an 21 antibiotic that a patient might be on; correct? 22 A. True. 23 Q. On this chart that you've made in assessing the 24 percentages or displaying the percentages, you have started 25 with 15 percent and gone up to 25 percent; correct? 163 1 A. Correct. 2 Q. A range of 10 percent; correct? 3 A. Correct. 4 Q. The Prozac patients, the percentage that you 5 came up with was about 24 percent, approximately? 6 A. About. 7 Q. And the imipramine percentage was just shy of 8 19; correct? 9 A. Yes. 10 Q. However, in your graphic depiction the 11 imipramine bar is twice as small -- or is half the size of the 12 Prozac graphic depiction, isn't it? 13 A. Yes. 14 Q. But in fact, you've got a Prozac value of 24 15 percent and, just for the sake of discussion, an imipramine of 16 19 percent and placebo right at 20 percent; correct? 17 A. Correct. 18 Q. So that just by viewing these bars alone you 19 certainly can't conclude that there were twice as many 20 fluoxetine patients on concomitant medication as imipramine; 21 correct? 22 A. Correct. 23 Q. You need to assess these values, which is the 24 precise indicator of what percentage of patients was on what 25 drug; correct? 164 1 A. Correct. 2 Q. Now, a number of the calculations or the 3 analyses that you've done have had to do with either the 4 Hamilton Depression Scale baseline total or the Hamilton 5 Depression Scale Item 3 at baseline; correct? 6 A. Correct. 7 Q. Do I understand correctly that you do not 8 regularly work with the Hamilton Depression Scale in your 9 research or in your professional time? 10 A. Correct. 11 Q. And you have not ever administered the Hamilton 12 Depression Scale to a patient, have you? 13 A. No. 14 Q. You would agree that the difference in a number 15 of the Hamilton Depression mean scores that you assessed is 16 quite small? 17 A. Yes. 18 Q. And you don't know the clinical significance of 19 those score differences, do you? 20 A. Could you define that? 21 Q. Well, for example, if a patient has a -- one 22 patient has a total score of a 23 and another patient has a 23 total of 24, you don't know the clinical meaning of what that 24 means in terms of patient's overall depression, do you? 25 A. In terms of whether they're more or less 165 1 depressed? 2 Q. Whether they're more or less depressed in their 3 total clinical picture. 4 A. I'm still unclear on the question. 5 Q. Well, let's assume you have a patient who has a 6 score of 23, okay? 7 A. Yes. 8 Q. And you have another patient who has a score of 9 24 on the Hamilton; correct? 10 A. Correct. 11 Q. You would agree with me that in assessing the 12 depression of the patient, the Hamilton Depression Scale is 13 just part of the picture that goes into assessing a patient 14 from a clinical standpoint? 15 A. Yes. 16 Q. And I take it you would leave the clinical 17 significance or the clinical implications to a trained 18 psychiatrist to sort out? 19 A. I believe they are filling out that form, yes. 20 Q. You would agree with me that the HAMD, and the 21 HAMD Item 3 specifically, is a commonly and widely used 22 measure of suicidal thinking, isn't it? 23 A. Yes. Item 3. 24 Q. All right, sir. Now, at the time you undertook 25 this review which was, what, about a year and a half ago? 166 1 A. Yes. 2 Q. All right. You had not reviewed any protocols 3 for any clinical trial prior to that time, had you? 4 A. No. 5 Q. And, in fact, I think immediately prior to your 6 deposition you were really not sure what the word protocol 7 meant, were you, sir? 8 A. It's used in a different way in psychology. 9 It's meant to be an individual subject's response. In this 10 case a protocol is -- the operational definition of the term 11 is quite different in the medical area. 12 Q. So in the setting where you are here today 13 testifying as an expert witness, protocol is used differently 14 than in your area of research in the academic world; correct? 15 A. Yes. 16 Q. Now, the first chart we looked at I think 17 depicted what you tallied to be a total of 78 studies; is that 18 correct? 19 A. Yes. 20 Q. The 40 and the 19 and the 19? 21 A. Correct. 22 Q. Did you review each and every protocol for those 23 studies, all 78? 24 A. How do you mean review? 25 Q. Did you read 78 different protocols for 78 167 1 different studies? 2 A. No. No. They were provided in summary form in 3 the literature provided to me. 4 Q. So you did not -- in answer to my question, you 5 did not read the individual protocols for 78 studies? 6 A. No. 7 Q. So I take it then you did not undertake to 8 assess if there was some sort of feature in the design of the 9 protocols or in the number of patients in the different 10 medication groups that might have accounted for the difference 11 in the mean HAMD scores that you detected? 12 A. No. 13 Q. You did not do that? 14 A. No. 15 Q. I'm correct you did not do that? 16 A. Yes. You are correct. My assumption was the 17 protocols were the same, essentially the same across studies. 18 Q. That was your assumption; correct? 19 A. Yes. 20 Q. But not having reviewed those, you cannot 21 confirm that assumption, can you? 22 A. I cannot confirm that. 23 Q. As I understand it, Professor Brown, the 24 concerns which you've expressed here today go to the subject 25 of the design of this research; correct? 168 1 A. Yes. 2 Q. You don't have any criticism with the specific 3 statistical techniques or methods that Lilly applied to this 4 data, do you? 5 A. No. 6 Q. You're assuming that those were applied 7 correctly, are you not? 8 A. Yes. 9 Q. All right, sir. I think that one of the charts 10 that you looked at had to do with the subject of recurrent and 11 single-episode depression. That was Plaintiffs' Exhibit 181; 12 is that correct? 13 A. Yes. 14 Q. And your tally indicated a higher percentage of 15 single-episode depression in the Prozac patients than 16 imipramine and placebo in one study? 17 A. No. This was Protocol 27, a compilation of 5 18 studies. 19 Q. That was a compilation as opposed to just Doctor 20 Bremner's study we talked about a minute ago? 21 A. Yes. Yes. 22 Q. All right, sir. And do I understand that you 23 really don't know what the psychiatric experts say about the 24 severity, the morbidity, the mortality or the treatment that's 25 associated with treating a single episode of depression as 169 1 opposed to recurrent depression, do you? 2 A. My assumption is that a recurrent-episode 3 depression is more severe than a single episode. 4 Q. That's your assumption, isn't it? 5 A. That's my assumption. 6 Q. I take it you would defer to the psychiatric 7 experts to make that assessment as to whether a single episode 8 of depression is worse than recurrent depression, wouldn't 9 you? 10 A. A clinical psychologist would be better able to 11 make that assessment. 12 Q. A clinical psychologist or a psychiatrist; 13 correct? 14 A. Correct. 15 Q. Someone in clinical practice; correct? 16 A. Yes. 17 Q. Someone that sees patients and treats patients; 18 correct? 19 A. Correct. 20 Q. All day, every day? 21 A. Not necessarily. They could be a clinical 22 psychologist on staff at SMU and they mainly teach, but they 23 could make that assessment. 24 Q. But, nonetheless, someone that devotes a 25 considerable percentage of their time to seeing and treating 170 1 depressed people? 2 A. True. 3 Q. Now, the Hamilton Depression Scale, which we've 4 heard a lot about over the course of this trial, that was 5 utilized in each of the trials that you reviewed, was it not? 6 A. Are you saying that the entire literature that I 7 received, every study had the Hamilton Depression Inventory? 8 Q. In the studies that you reviewed and that you 9 evaluated, was that included as part of the study? 10 A. I believe it was. There may have been a few 11 that did not have that, but the vast majority had that. 12 Q. All right. And it's your assumption that the 13 Hamilton, and particularly Item 3, is an accurate predictor of 14 suicidal thinking and acts; correct? 15 A. My assumption is that Lilly would not have used 16 that unless it were. 17 Q. And you are aware that there is a risk to 18 depressed patients, that is, patients with major depressive 19 disorder for suicide? 20 A. Yes. 21 Q. And, in fact, I think you've told us before that 22 10 to 20 percent of patients who are diagnosed, as far as you 23 know, are at risk of completing suicide; isn't that correct? 24 A. Yes. 25 Q. You understand that suicidal acts and thinking 171 1 may change over time? 2 A. Yes. 3 Q. For example, in the studies that you reviewed, 4 there was an exclusion criteria that the patient, if the 5 patient was a severe or serious suicidal risk at the time of 6 enrollment could not get into the study; correct? 7 A. That was my assumption. There seemed to be a 8 few that did get in, but my assumption was it was the primary 9 exclusion. 10 Q. It was a primary exclusion criteria? 11 A. Yes. 12 Q. And that that was an assessment that would be 13 made at the time the patient enrolled by the clinical 14 investigator who was assessing the patient; correct? 15 A. Yes. 16 Q. That was a clinical judgment before the patient 17 went into the trial; correct? 18 A. Yes. 19 Q. And before the patient was ever randomized to 20 drug or placebo; correct? 21 A. Correct. 22 Q. Now, you also know from your review of this data 23 that there were patients in the clinical trials who scored 24 somewhere between zero and four on their Hamilton Depression 25 Scale at some point during the trial; correct? 172 1 A. They had to, but I don't understand the 2 question. 3 Q. Well, the Hamilton Depression Scale was included 4 as a measure of depression during the trials; correct? 5 A. Yes. 6 Q. And Item 3 on the scale assesses suicidality? 7 A. Correct. 8 Q. And that item is scored zero to four; correct? 9 A. Correct. 10 Q. And, in fact, we have Plaintiffs' Exhibit 123, 11 which is already in evidence, is a copy of the Hamilton 12 Depression Scale. Have you ever seen one of these before, 13 Professor? 14 A. Yes. That was in the materials supplied. 15 Q. So you've reviewed this? 16 A. Yes. I looked at that. 17 Q. And you would agree with me that the ratings for 18 the Hamilton, ranging from zero to four -- zero means that 19 it's absent; correct? 20 A. Yes. 21 Q. One, is feels life is not worth living; correct? 22 A. Yes. 23 Q. Two, wishes he were dead or any thoughts of 24 possible thoughts of death to self; correct? 25 A. Yes. 173 1 Q. Three, suicide ideas or gestures; correct? 2 A. Yes. 3 Q. The person has some ideas or actually makes some 4 sort of an overt gesture; correct? 5 A. Yes. 6 Q. And Number Four is attempts suicide; correct? 7 A. Yes. 8 Q. And that during the clinical trials which you 9 reviewed there were some patients who scored zero at one time 10 or another; correct? 11 A. Yes. 12 Q. And patients who scored anywhere between one and 13 four at one time or another; correct? 14 A. Yes. 15 Q. Because these were depressed patients who were 16 in these trials, were they not, sir? 17 A. Yes. 18 Q. And the depressed patient is always at risk for 19 suicide; correct? 20 A. Yes. 21 Q. Ranging from on the one end some feelings of 22 guilt to the other extreme, an attempt or an actual act; 23 correct? 24 A. Yes. 25 Q. You would agree with me, wouldn't you, that the 174 1 admission of patients at serious suicidal risk into a clinical 2 trial might pose an ethical problem for the clinical 3 investigator undertaking to conduct that trial? 4 A. I'm not sure. It depends on the circumstances. 5 You're speaking of outpatient or inpatient? 6 Q. Yeah. Let's assume an outpatient clinical 7 trial. 8 A. That would be a possibility. 9 Q. You understand, don't you, sir, that when 10 clinical trials are set up and instituted and put in place, 11 the investigator has to go before -- and the protocol has to 12 go before what's called an institutional review board? 13 A. Yes. 14 Q. Tell the jury what an institutional review board 15 is, as you understand it. 16 A. Every institution has to have one of those, and 17 that's a way to protect human and nonhuman organisms from -- 18 protect them to make sure procedures of the research don't 19 cause any harm, psychological or physical. 20 Q. And, in fact, I think you told us that you did 21 do a study, though not a clinical study, in people one time 22 that you had to run by an institutional review board; correct? 23 A. Well, technically all my research has to go 24 through SMU's IRB and I've gone through other IRBs. 25 Q. So you're familiar with the process? 175 1 A. Yes. 2 Q. And a criteria which allowed a serious suicidal 3 patient on intake into a clinical trial might well pose some 4 problems from an institutional review board standpoint? 5 MR. SMITH: Objection to that, Your Honor. 6 Calls for him to speculate. 7 JUDGE POTTER: Objection is overruled. 8 A. You're speaking of an outpatient study? 9 Q. Sure. 10 A. That could potentially be problematic. 11 Q. You talked a little bit with Mr. Smith about the 12 subject of a placebo washout period in the clinical trials. 13 Do you remember that? 14 A. Yes. 15 Q. You recognize, don't you, sir, that a placebo 16 washout is a standard component of this type of clinical trial 17 research, don't you? 18 A. Yes. 19 Q. And it's a standard part of psychiatric clinical 20 trials? 21 A. That's what I've been told. 22 Q. And you have not done any literature review or 23 any independent research into the propriety of a placebo 24 washout, have you? 25 A. No. 176 1 Q. You would agree with me, wouldn't you, sir, that 2 the design of clinical trials, that is, studies to look at a 3 drug in a diseased population pose some design challenges for 4 the people putting them together, don't they? 5 A. Yes. 6 Q. It is not possible in your view, is it, to 7 design the perfect clinical trial? 8 A. It is possible to design it. Now, whether it's 9 possible to implement it is the issue. 10 Q. So one might take pen to paper and design the 11 ideal clinical trial, the perfect clinical trial, but it would 12 be very difficult, wouldn't it, to carry it out? 13 A. With outpatients. 14 Q. Because patients, like depressed patients, may 15 have other features to their illness; correct? 16 A. That's correct. 17 Q. For example, they might have some type of a 18 substance abuse problem; correct? 19 A. Now, are we speaking in general or with respect 20 to the research under discussion? 21 Q. Well, first in general. 22 A. Yes. 23 Q. And they may have socioeconomic impacts on their 24 lives; correct? 25 A. Could you clarify that? 177 1 Q. Sure. Financial problems, marital difficulties. 2 A. You mean in their everyday life, not with 3 respect to the medical trials? 4 Q. In addition to their illness. 5 A. Yes. 6 Q. They may have a concomitant or another 7 condition; correct? 8 A. That's possible. 9 Q. Might have high blood pressure; correct? 10 A. Yes. 11 Q. Which needs medication; correct? 12 A. Correct. 13 Q. Might have a heart condition which needs 14 medication; correct? 15 A. Yes. 16 Q. Might have an infection which needs an 17 antibiotic treatment; correct? 18 A. Yes. 19 Q. On the subject of concomitant medications, you 20 understand, do you not, sir, that the patients in these trials 21 are voluntary patients; correct? 22 A. Yes. 23 Q. And that they may enter the trial with a 24 concomitant medical condition; correct? 25 A. Yes. 178 1 Q. And that medical condition may need treatment; 2 correct? 3 A. Yes. 4 Q. Now, you have never been a clinical 5 investigator, have you? 6 A. I have participated in clinical research 7 projects as a collaborator. 8 Q. Have you ever been a clinical investigator in a 9 pharmaceutical trial? 10 A. No. 11 Q. Have you ever worked for a pharmaceutical 12 company? 13 A. No. 14 Q. Have you ever consulted a pharmaceutical company 15 on the design of clinical trials? 16 A. No. 17 Q. Have you ever worked at the FDA? 18 A. No. 19 Q. And I take it you've not been a consultant to 20 the FDA or any of its advisory committees? 21 A. No. 22 Q. Now, when Mr. Smith was completing his 23 examination of you, you went through a number of charts and 24 graphs concerning spontaneous drug experience data; correct? 25 A. Yes. 179 1 Q. And I think that that was reflected, so that 2 maybe the jury can follow, in Plaintiffs' Exhibit 120; 3 correct? Oh, this is 186, originally introduced as 4 Plaintiffs' Exhibit 120. Do you see that? 5 A. I have 186, yes. 6 Q. What is your PZ number range that you have 7 there, sir? 8 A. Nineteen hundred to nineteen thirteen. 9 Q. All right. That's what we have here. As I 10 understand it, your first review of any of this drug 11 experience report spontaneous data was the day before your 12 deposition on September the 15th in Dallas; is that correct? 13 A. This particular document I saw the day before my 14 deposition. 15 Q. And that was in a meeting with Mr. Smith and Ms. 16 Zettler; correct? 17 A. Correct. 18 Q. You don't, of your own knowledge, have any 19 familiarity with the regulations surrounding reporting events, 20 do you, except as you told us in your deposition as explained 21 to you by Mr. Smith? 22 A. Yes. 23 Q. You would agree with me that there are and can 24 be many biases in spontaneously reported drug events? 25 A. Yes. 180 1 Q. And that those biases could in fact potentially 2 skew that data? 3 A. Yes. 4 Q. You understand that these data, these -- well, 5 let's back up a second. 6 You understand that these spontaneous reports 7 are made once the drug is marketed; correct? 8 A. Yes. 9 Q. That's something different from an event that 10 might occur in a clinical trial? 11 A. Yes. 12 Q. And you understand that these spontaneous 13 reports come from many courses, don't you? 14 A. Yes. 15 Q. They could include medical practitioners; 16 correct? 17 A. Yes. 18 Q. They could include patients? 19 A. Yes. 20 Q. They could include reports from the medical 21 literature? 22 A. I assume so. 23 Q. They could include reports from the media? 24 A. If you say so. I'm taking your word for that. 25 Q. This data is -- it's uncontrolled data; correct? 181 1 A. Yes. 2 Q. And you understand that the incidence rate for 3 reporting of new drugs is more than it is for older drugs; 4 correct? 5 A. Yes. 6 Q. And in the graphs that Mr. Smith showed you 7 earlier, Prozac was clearly the newer drug of the drugs to 8 which it was compared? 9 A. Yes. 10 Q. You would agree that it's dangerous to draw 11 conclusions particularly concerning causation simply from this 12 data? 13 A. Yes. And I didn't do that. 14 Q. You did not do that? 15 A. I didn't draw conclusions just based on this 16 data. 17 Q. And you would agree that to draw conclusions 18 just based on this data would be very dangerous? 19 A. Solely on the basis of this data, it would be 20 problematic. 21 Q. You would agree that one should be cautious in 22 drawing conclusions from this data? 23 A. On naturalistic data, I instruct my students to 24 be careful. 25 Q. You would agree with me that, for example, 182 1 publicity concerning a drug could contribute to an influx of 2 reports on the drug; correct? 3 A. Yes. 4 Q. And the fact that the drug is new could 5 contribute to the volume of reports; correct? 6 A. Yes. 7 Q. And as I understand it, the data that you were 8 shown and as is reflected in Plaintiffs' Exhibits 120 and 186 9 was spontaneous data reported through July of 1991; is that 10 right? 11 A. I believe so. 12 Q. And you've not looked at any data after July of 13 1991 on reporting rates for fluoxetine, have you? 14 A. I don't believe so. 15 Q. And so I take it you don't have any basis from 16 which to judge what the trend has been in that reporting for 17 the last three years? 18 A. No. 19 Q. You would agree with me that the way in which a 20 pharmaceutical company reports, that is, if it's aggressive in 21 reporting adverse events and collecting as many events as 22 possible, could contribute to the number of events reported? 23 A. That could contribute. 24 Q. Did you know, Professor, that the graphs 25 contained in Exhibits 120 and 186 were the FDA's graphs from 183 1 its September of 1991 advisory committee meeting? 2 A. Are you asking me if I knew that? 3 Q. Do you know that? 4 A. No. 5 Q. Okay. Did you attend the 1991 advisory 6 committee meeting? 7 A. No. 8 Q. Have you been furnished a transcript by the 9 Plaintiffs of the proceedings of the September of 1991 10 advisory committee meeting? 11 A. No. 12 Q. You have, however, reviewed and expressed 13 opinions here today about the submission that Lilly made to 14 that advisory committee meeting; correct? 15 A. Yes. 16 Q. Did you know that the FDA had a 17 psychopharmacological drugs advisory committee? 18 A. No. 19 Q. Did you know that the FDA has outside experts 20 from academia and medical institutions from around the country 21 that advise it in connection with these kinds of drugs? 22 A. No. 23 Q. Did you know that in September of 1991 that 24 advisory committee convened a meeting to consider the question 25 of whether antidepressants, including Prozac, were related to 184 1 suicidality or violent-aggressive behavior? 2 MR. SMITH: Could we approach the bench, Your 3 Honor? 4 (BENCH DISCUSSION) 5 MR. SMITH: He's now going beyond the scope 6 which this Witness was put on for and he's just putting on his 7 entire case, defense, through this Witness who has nothing to 8 do but to agree with him. This is improper cross-examination, 9 Your Honor. He's not questioning him about his credentials, 10 about his opinions or anything. 11 MR. MYERS: Judge, my position is simply this: 12 He was taken in excruciating detail through the exhibits which 13 we know were the FDA's exhibits at that meeting as testified 14 to by Doctor Thompson, and I'm entitled to examine him about 15 that meeting and that data since he has clearly expressed 16 opinions about it. 17 JUDGE POTTER: Mr. Smith, I think you're correct 18 that he is going beyond direct, but in Kentucky you can go 19 beyond direct on cross. 20 MR. SMITH: I understand that. 21 JUDGE POTTER: I think you are correct that he's 22 putting in part of his case, but I don't think he can put in 23 his whole case that way. But as long as he limits it to the 24 very meeting where your guy got his summaries that he 25 rejiggled and criticized, I think he can bring out the fact 185 1 that what the actual meeting was and the people that were 2 actually there came to a different conclusion. Objection is 3 overruled. 4 MR. SMITH: Wait a second. Could we get some 5 limits on this? 6 JUDGE POTTER: As long as it stays around that 7 1991 thing. 8 (BENCH DISCUSSION CONCLUDED) 9 Q. Let me ask you this, Professor. Have you ever 10 talked with anyone at the FDA about their data or their 11 analyses of this data? 12 A. No. 13 Q. And I think you've told us you have not reviewed 14 the transcript of the proceedings from the advisory committee 15 meeting? 16 A. No. 17 Q. Did you know that these very charts in Exhibits 18 120 and 186 were presented at the advisory committee meeting 19 by the FDA's own statistician, Doctor Stodel? 20 A. No. 21 Q. And that the advisory committee and its 22 consultants considered this data along with the Lilly 23 submission which you've considered; did you know that? 24 A. No. 25 Q. Were you aware that in two separate votes -- 186 1 MR. SMITH: That's a mischaracterization of what 2 was done at the committee meeting. Professor Stodel never 3 discussed these statistics with that committee. It's a 4 mischaracterization of what occurred. 5 JUDGE POTTER: Mr. Myers, I think you need to 6 ask your questions without assuming facts that aren't in 7 evidence yet. 8 Q. Are you aware, Professor Brown, about the 9 outcome of that meeting? 10 A. No. 11 Q. Are you aware that the FDA committee voted 12 unanimously that there was no credibile evidence associating 13 Prozac in suicide or violent behavior? 14 MR. SMITH: Object to that, Your Honor. It was 15 not a unanimous decision. 16 JUDGE POTTER: Why don't you state exactly what 17 it is, Mr. Myers. 18 MR. MYERS: Would you like for me to state it 19 directly from the transcript, Your Honor? 20 JUDGE POTTER: Yes. 21 Q. Are you aware that the advisory committee took 22 two separate votes at that meeting in September of 1991, where 23 they reviewed this adverse experience data that you've been 24 shown here today and that you earlier reviewed? 25 MR. SMITH: There's nothing said about that in 187 1 this adverse experience data in this in connection with these 2 exhibits. 3 JUDGE POTTER: Let me see you up here just a 4 minute. 5 (BENCH DISCUSSION) 6 MR. MYERS: Page 138 to 170 Doctor Stodel says, 7 "I'm going to be talking about the experience of the Food and 8 Drug Administration spontaneous reporting system," and then he 9 goes on to Page 170 on the subject. 10 MR. SMITH: And never mentioned those exhibits. 11 Never mentioned them. 12 JUDGE POTTER: Just so that we don't get stuff 13 in evidence and the questions that assumes stuff that is not 14 in evidence, why don't you ask him if he knows what the 15 outcome was, whether he knows whether or not that stuff was 16 there and then go on. 17 (BENCH DISCUSSION CONCLUDED) 18 Q. Professor Brown, are you aware of the outcome of 19 the September 1991 advisory committee meeting? 20 A. No. 21 Q. Mr. Smith nor Ms. Zettler have disclosed that to 22 you? 23 A. I may have read it in the materials and 24 forgotten it. 25 Q. May have forgotten it? 188 1 A. Yes. 2 Q. All right. Nothing further. 3 JUDGE POTTER: Mr. Smith? 4 5 FURTHER_EXAMINATION _______ ___________ 6 7 BY_MR._SMITH: __ ___ ______ 8 Q. Mr. Brown -- Doctor Brown, since we're talking 9 about this fluoxetine versus Trazodone, do you understand that 10 this is reports and this is data not controlled by the Lilly 11 clinical trials? 12 A. Yes. 13 Q. Do you understand that this is data and reports 14 made by citizens in connection with this product? 15 A. Yes. 16 Q. Medical doctors in connection with this product? 17 A. Yes. 18 Q. Health-care practitioners in connection with the 19 product? 20 A. Yes. 21 Q. Doctors who were seeing patients and observing 22 the reaction of this drug in real, live patients? 23 A. Yes. 24 Q. You understand that? 25 A. Yes. 189 1 Q. Do you understand Lilly couldn't control this 2 data? 3 A. Yes. 4 Q. This doesn't come from the Lilly clinical 5 trials, does it? 6 A. That's correct. 7 Q. Is that of any significance to you? 8 A. Yes. 9 Q. Why? 10 A. Well, the two -- that is important because it is 11 in such stark contrast to the clinical trials that it 12 indicates that something isn't right in terms of the research, 13 or it certainly suggests that that would be the case. And the 14 other thing about this, although I warn my students against 15 taking anecdotal or naturalistic data too seriously, I'm 16 usually talking about small effects. If there's enormous 17 differences like this, that increases your confidence that 18 there must be something going on. It doesn't say that there 19 is a surety, that there is a cause/effect, but there is 20 something -- there's something going on that's very dramatic 21 in this case. 22 Q. Since you're a psychologist and a statistician, 23 is the term "where there's smoke there may be fire" applicable 24 in statistics or psychology, or is that just common sense? 25 MR. MYERS: Your Honor, objection. 190 1 JUDGE POTTER: Mr. Smith, sustain the objection. 2 Leading, if nothing else. 3 Q. Those are not psychological or statistical 4 terms, are they? 5 A. No. 6 Q. You're talking about, or Mr. Myers was talking 7 about bias potentially skewing data. Do you follow what I'm 8 saying? 9 A. In this particular data set? 10 Q. Yeah. Let's talk about the fact that this was a 11 new drug, that there was publicity, that these other 12 antidepressants were well known. 13 A. Yes. 14 Q. From a statistical and from a research method 15 and design, would you expect to see, even if there was some 16 influence, would you expect to see this vast amount of 17 difference, Doctor Brown? 18 A. Well, it is surprising to see that large a 19 difference that quickly. Certainly it's a stark contrast. 20 Q. If you cut it in half it would be a stark 21 contrast, wouldn't it, Doctor Brown? 22 A. Yes. 23 Q. And that's adjusted, is it not, sir, so we'll 24 understand, based on reports per million prescriptions? That 25 doesn't take into account the enormous difference in the 191 1 popularity of these two drugs, does it? 2 A. That does adjust for the difference in 3 prescriptions, yes. 4 MR. SMITH: Let me clear up a few things real 5 quick. Can I do that, Your Honor, or do you want to take a 6 break? 7 JUDGE POTTER: No. Why don't you go ahead and 8 finish with the Witness, Mr. Smith. 9 Q. On Exhibit 179, where you took the baseline 10 HAMD-3 scores -- 11 A. Yes. 12 Q. -- do you see that? 13 A. Yes. 14 Q. Mr. Myers would suggest that you put all of this 15 stack on top of this stack to make the description more 16 accurate. Why didn't you do that? 17 A. Well, there are several ways I could do that. I 18 could split the equal group in two and put nine and a half on 19 top of each; that's one way to do it. 20 Q. So you would take half of this and put it there, 21 and half of this and put it there? 22 A. Yes. It doesn't make any sense to do what he 23 did, but there are other ways to present it, I do agree. 24 Q. But is this the most accurate way in your 25 judgment to present the fact that there were 40 studies where 192 1 the HAMD scores, Item 3 mean scores, were lower on Prozac on 2 patients to start out? 3 A. That seemed to be the best way to present it. 4 Q. Forty out of seventy-eight? 5 A. Correct. 6 Q. Over half the Prozac people started out at a 7 lower score? 8 A. In over half of the studies, because there's 9 different numbers of people in each study. 10 Q. Okay. Mr. Myers also made something of the fact 11 that you didn't review the 78 protocols to determine whether 12 or not there might be any explanation in the protocols for why 13 there would be 40 studies, more than half the studies where 14 the people would start off better on Prozac. Can you imagine 15 any clinical trial protocol that would have a drug under study 16 where they would intentionally put people under the protocol 17 starting off better, less-depressed people on the drug that's 18 being investigated? 19 A. Are you asking me to speculate as to why that 20 was done? 21 Q. No. Would there be any reason for a protocol to 22 put that in writing to start their own people off better? 23 A. No. No. 24 Q. On the chart on concomitant medications, 25 Exhibit 184, why did you start off with 15 on the bottom of 193 1 the graph and 25 on the top of the graph? 2 A. That was meant to emphasize the differences. 3 The one thing I'd like to add, though, to that, is aside from 4 whether or not there are differences between Prozac and the 5 other two groups, the presence of 1 in 5 or more of the 6 individuals having concomitant medications raises a flag 7 regardless of how they're distributed across groups. It 8 muddies the comparison. 9 Q. The point is there should be an equal amount; 10 right? 11 A. Yeah. And even at that, it would still be a bad 12 design. 13 Q. That's all I have. Thank you, Doctor Brown. 14 JUDGE POTTER: Thank you very much, sir. You 15 may step down. 16 Ladies and gentlemen, we're going to take the 17 afternoon recess. As I've mentioned to you-all before, do not 18 permit anybody to talk with you or communicate with you on any 19 topic connected with this trial; do not discuss it among 20 yourselves; do not form or express any opinions. Let's take a 21 15-minute recess. 22 (RECESS) 23 SHERIFF CECIL: The jury is entering. All 24 jurors are present. Court is back in session. 25 JUDGE POTTER: Mr. Smith, do you want to call 194 1 your next witness? 2 MR. SMITH: Yes, Your Honor. We would call 3 Doctor John Heiligenstein by deposition. 4 JUDGE POTTER: Ladies and gentlemen, I know 5 you're tired of hearing me say certain things over and over 6 and over again, but the reason I say it is because it's 7 important and it's something you might forget. A deposition 8 is sworn testimony. It's taken outside the courtroom prior to 9 trial. Both sides have an opportunity to be present and 10 examine and cross-examine the witness just the way they do at 11 trial. When that testimony is either read to you or played to 12 you by deposition, you'll give it the same weight and effect 13 you would if the witness were here testifying live. 14 15 (THE FOLLOWING PORTIONS OF DR. HEILIGENSTEIN'S 16 DEPOSITION WERE READ BY MR. SMITH AND MR. STEIN) 17 18 MR. SMITH: This is the deposition of Doctor 19 John H. Heiligenstein taken on April 27th, 28th and 29th. The 20 following deposition of John H. Heiligenstein, M.D., was taken 21 at the offices of Baker & Daniels, 300 North Meridian Street, 22 Suite 270, in Indianapolis, Indiana 46204, on April 27th, 28th 23 and 29th; said deposition taken pursuant to notice in 24 accordance with the Rules of Civil Procedure. Questions 25 beginning on Page 13, Line 3. 195 1 Q. Could you state your full name for the record? 2 A. John Harrison Heiligenstein. 3 Q. And what is your current address? 4 A. 1202 West 56th Street, Indianapolis, 46208. 5 Q. How long have you lived there? 6 A. Two and one-half years. 7 Q. Have you ever served in the military? 8 A. I have. 9 Q. Can you tell us about that? 10 A. From 1974 through 1976, I was a major in the 11 United States Army, chief of pediatrics in Fort Sheridan Army 12 Health Center in Fort Sheridan, Illinois. 13 Q. Up in Highland Park? 14 A. That's correct. 15 Q. Were you chief of pediatrics at Fort Sheridan 16 from 1974 to 1976? 17 A. That's correct. 18 Q. I take it that's treating family members of 19 people in the service; correct? You weren't treating people 20 who were in the army, obviously? 21 A. Dependents. 22 Q. Was that an honorable discharge? 23 A. Correct. 24 Q. Could you list for us your education past high 25 school? 196 1 A. Okay. The years or just the... 2 Q. The years, places and degrees. 3 A. It's long. 4 Q. Okay. 5 A. From 1963 to '67 I attended the University of 6 Illinois in Urbana, had my Bachelor's Degree from that 7 university. From 1967 through 1971, I attended Loyola 8 University, Stritch School of Medicine in Maywood, Illinois, 9 from which I obtained my M.D. From 1971 through 1973, I was a 10 pediatric resident at Children's Memorial Hospital in Chicago, 11 part of the Northwestern family of hospitals. From 1973 12 through 1974 -- a year, July to July is usually the running 13 dates for residency programs -- I was a Fellow in neurology at 14 the University of Kentucky Medical Center in Lexington 15 Kentucky. From '74 to '76, as I mentioned, I was in the 16 military. From 1976 to 1978, I was a Fellow and chief 17 resident for the second year of child, adolescent and family 18 psychiatry at the University of Virginia Medical Center in 19 Charlottesville, Virginia. From 1978 through the end of 1979, 20 so for 18 months, I was a resident in general psychiatry at 21 Cornell University Medical Center, the White Plains campus. 22 Q. I'm sorry. A resident in what? 23 A. General psychiatry. 24 Q. Is that it? 25 A. As far as education, formal education, yes. 197 1 Q. Are you board certified? 2 A. Yes, I am. 3 Q. In what areas? 4 A. I have my boards in pediatrics, in psychiatry, 5 and in child and adolescent psychiatry. 6 Q. Besides your formal education have you taken any 7 seminars or other continuing education-type classes in 8 psychiatry or psychology? 9 A. Yes, I have. 10 Q. Could you list those for us, please, as many as 11 you can remember? 12 A. I attend regularly the child and adolescent 13 psychiatry meetings where there are specific workshops and 14 symposia offered. In those meetings I have tended to focus on 15 disorders of childhood and then selected topics in general 16 psychiatry. In addition, I have attended the American 17 Psychiatric Association meetings on an irregular basis and 18 have attended symposia and workshop at those meetings, very 19 much along the same lines. 20 Q. Stressing mostly adolescent psychiatry? 21 A. In those arenas it was primarily disorders of 22 affect, anxiety spectrum disorders, and to some extent 23 psychotic disorders of adults. 24 Q. I'm sorry. Anxiety what disorders? 25 A. Anxiety spectrum. I've also attended others, if 198 1 you're interested. 2 Q. Sure. 3 A. I've attend biological psychiatry meetings where 4 there are full-day symposium. I've attended the American 5 College of Neuropsychiatry meetings on an irregular basis. I 6 mean, every couple years I go usually, with the opportunity to 7 participate in similar such workshops to those I described at 8 the APA. The Congress of International 9 Neuropsychopharmacology meetings, I've attended two or three 10 of those. I've attended some meetings of the American Society 11 of Adolescent Psychiatry and the International Society of 12 Adolescent Psychiatry, at least one occasion for each of 13 those, with again participation as an attendee in workshops. 14 I attend fairly regularly the NCDEU meetings, which are held 15 usually in June in Florida. I've attended courses when I was 16 in practice that were offered through the American Academy of 17 Child and Adolescent Psychiatry. Review courses, I've also 18 attended selected review courses that are offered through 19 Harvard University, their program. 20 Q. Since 1979, when you completed your residency at 21 Cornell University, have you been in private practice? 22 A. I have been. 23 Q. Can you tell us about your private practice? 24 A. I began private practice in 1982 in Greensboro, 25 North Carolina, and then I returned to Charleston, South 199 1 Carolina, where I was in private practice until September of 2 1986, when I came to Lilly. I left Lilly in July of 1987 and 3 was director of a child inpatient unit at Lutheran General 4 Hospital in Parkridge, Illinois, and then I returned to Lilly 5 May the 3rd or 4th of 1988 and I have been here since. 6 Q. What did you do from 1979 to 1982? 7 A. I was an assistant professor of pediatrics and 8 psychiatry at the Medical University of South Carolina in 9 Charleston, South Carolina. 10 Q. In your private practice in 1982 through 11 September of '86, when you first joined Lilly, was that 12 psychiatric practice? 13 A. That's correct. 14 Q. General psych or adolescents or child psych? 15 A. I focused very heavily on child and adolescent 16 psychiatry, family psychiatry. 17 Q. I'm sorry. You say when you were at Lutheran 18 General you ran which department? 19 A. I was responsible for the child inpatient 20 psychiatry unit. 21 Q. Why did you come back to Lilly in May of '88? 22 A. Pardon? 23 Q. Why did you come back to Lilly in May of '88? 24 A. I really enjoyed what I was doing when I was 25 here, so I wanted to get back into an active role in research 200 1 and development of compounds. 2 Q. And you've been at Lilly consistently to the 3 present since May of '88? 4 A. That's correct. 5 Q. Now, from when you left Lilly in July of '87 6 until you came back to Lilly in May of '88, did you prescribe 7 fluoxetine to any patients? 8 A. Yes. 9 Q. Tell us about those occasions. 10 A. It was just one patient. 11 Q. Is that patient an adult or an adolescent? 12 A. Child. 13 Q. How about Jan Fawcett, do you know who Jan 14 Fawcett is? 15 A. Yes, I do. 16 Q. Who is Jan Fawcett? 17 A. Jan Fawcett is a professor and psychiatrist at 18 Rush Presbyterian Hospital in Chicago, Illinois. 19 Q. What school is he a professor with? 20 A. I believe that's the Rush Medical School. 21 Q. Have you ever spoken with Doctor Fawcett? 22 A. Yes, I have. 23 Q. On what occasions? 24 A. Usually while attending various scientific 25 meetings. 201 1 Q. Have you spoken with Doctor Fawcett about 2 fluoxetine? 3 A. Yes, as best I can recall. 4 Q. Are you aware that Doctor Fawcett participated 5 in at least one clinical trial on fluoxetine? 6 A. I recollect that. 7 Q. Have you ever spoken with Doctor Fawcett about 8 that clinical trial? 9 A. Not that I recall. 10 Q. Have you ever spoken with Doctor Fawcett about 11 the issue of violent-aggressive behavior in patients on 12 fluoxetine? 13 A. Violent-aggressive behavior directed towards 14 self? 15 Q. Directed towards others. 16 A. No, I have not. 17 Q. How about directed towards self? 18 A. Yes. 19 Q. On what occasion did you speak with Doctor 20 Fawcett about that topic? 21 A. As best I recall, Doctor Fawcett was a 22 consultant that we engaged to help us explore the issue of 23 suicidality. 24 Q. Was that before or after the 1991 drug advisory 25 committee meeting? 202 1 A. That would have been prior to that meeting. 2 Q. Where was this conversation with Doctor Fawcett? 3 Where did that take place? 4 A. It would have occurred at Lilly. 5 Q. Did you have a one-on-one conversation with 6 Doctor Fawcett or was it a meeting in which Doctor Fawcett 7 participated? 8 A. It was more in the format of a formal meeting 9 and discussion. 10 Q. When did these meetings with the consultants 11 take place? 12 A. That, I don't recall. 13 Q. Was it before or after January of 1990? 14 A. I believe it was after January of 1990. 15 Q. To your knowledge, has Doctor Fawcett ever been 16 a member of Lily's psychiatric advisory panel? 17 A. That's my recollection. 18 Q. Would you tell us about that panel? Generally 19 when it was begun, how many times it met, things of that 20 nature. 21 A. I don't know when it was organized and I don't 22 know with what frequency it met. 23 Q. Was it organized before you came to Lilly in 24 September of '86? 25 A. As best I recall, it was. 203 1 Q. How many members were on the panel? 2 A. I don't know. 3 Q. More than ten? 4 A. I don't know. 5 Q. Did you ever attend any meetings where the panel 6 was convened? 7 A. I have. 8 Q. On how many occasions? 9 A. Two or three. 10 Q. What was the first one that you attended? 11 A. It would have been sometime in 1986 or 1987. 12 Q. When you were a physician in the army, did you 13 participate in any way in clinical trials on medications? 14 A. I did not. 15 Q. Other than providing medical services to 16 dependents of enlistees, what were your job capacities, what 17 were your duties outside your duties as a major in the army? 18 A. My time with the army was spent providing care 19 to those dependents. In addition, during that time I had a 20 faculty appointment at the Medical College of Wisconsin in 21 Milwaukee where I volunteered my services on a once or twice 22 monthly basis to the child neurology program. 23 Q. I take it you've published some papers in the 24 area of psychiatry, have you not? 25 A. I have. 204 1 Q. Would you give us an idea of how many papers you 2 published throughout your career, not just at Lilly? 3 A. That have been published or in press? 4 Q. Right. Let's start with have been published. 5 A. I would say somewhere on the order of eight or 6 nine. 7 Q. Can you list as many of those for us as you can 8 remember? 9 A. Sure. I published a paper that involved meta 10 analysis of events of aggression occurring during clinical 11 trials with fluoxetine. A less-extensive version of that 12 paper was also published, so there were two publications 13 related to the same topic. I participated in the publication 14 of a paper relative to events occurring with co-prescribing of 15 fluoxetine and monoamine oxidase inhibitors. I've published 16 relative to the efficacy of fluoxetine in patients with 17 melancholia. There are two papers relative to melancholia. 18 Q. Both on efficacy of fluoxetine in treating that 19 condition? 20 A. That's correct. I participated in the 21 publication of the paper relative to suicidality, the analysis 22 of the data. 23 Q. Doctor Beasley's meta analysis article? 24 A. The first publication. 25 Q. The publication that appeared in the British 205 1 Medical Journal? 2 A. That's correct. 3 Q. How about the republication and reprint? 4 A. I do not believe -- I cannot recall 5 participating in that. Those are the ones I can recall of. 6 Q. Any others on violent-aggressive behavior and 7 the use of fluoxetine? 8 A. No, not that I recall. 9 Q. Any others on suicidality related to the use of 10 fluoxetine? 11 A. None that I recall. 12 Q. All of these papers were published, I take it, 13 throughout your career at Lilly? 14 A. That's correct. 15 Q. How about outside your career at Lilly, have you 16 published anything? 17 A. I have not. 18 Q. You said that there were some papers that were 19 currently in press? 20 A. That's correct. 21 Q. Can you tell us what those papers are? 22 A. One is a paper which I co-authored on design 23 strategy, and I believe that will appear in the Journal of the 24 American Statistical Association. An additional paper will be 25 published relevant to the efficacy of fluoxetine in patients 206 1 who have a reduced eye movement latency. 2 Q. How about people in clinical trials on 3 fluoxetine who have committed violent acts, are you aware of 4 any such situation where somebody in a clinical trial has 5 become violent or committed a violent act? 6 A. Well, I participated in an analysis of the data 7 from the clinical trials. 8 Q. I know that. 9 A. So in that process we sought to identify 10 individuals who would have met criteria who would have been 11 violent towards others. 12 Q. So what's the answer to my question? Are you 13 aware of anybody who has become violent during a fluoxetine 14 clinical trial? 15 A. I recollect that there were patients who may 16 have become violent during clinical trials. 17 Q. What criteria did you use when you reviewed the 18 databases? 19 A. It's very long. 20 Q. What is the criteria, Doctor? 21 A. To give you the criteria, I would like to go 22 through the process. 23 Q. Sure. 24 A. We wanted to address this particular issue as 25 scientifically as possible with the search of the database 207 1 remaining blinded to those individuals responsible for the 2 leadership of the meta analysis, which primarily resided in my 3 domain, so I was primarily responsible for that. 4 Q. So you were blinded is what you're saying? 5 A. That's correct. In discussing this with several 6 individuals, we first went through the postmarketing adverse 7 events, and what we did is we looked through the dictionary 8 listing, that means either the ELECT or the COSTART 9 dictionaries, whatever dictionary we used during the course of 10 those clinical trials. 11 Q. Well, let me interrupt you. First you said you 12 went through the postmarketing adverse events? 13 A. I'm sorry. 14 Q. So are we in postmarketing or clinical trials? 15 A. We're in postmarketing. 16 Q. Okay. 17 A. We didn't want to look at the clinical trial 18 database until we knew how best to look at that clinical trial 19 database. So as best I recollect, we went through the 20 dictionary and collected all those terms that could possibly 21 have incorporated as a component of that event a violent 22 expression toward another. 23 Q. Okay. 24 A. We selected all those events and then ran an 25 output from postmarketing reports. 208 1 Q. The DEN database? 2 A. That's correct. Of all such events that had 3 been reported to us. We then reviewed each of those reports 4 and we established -- we identified from clinical trials as I 5 best recall, eight or ten such occurrences. We then selected 6 from the larger pool of events those that would most likely -- 7 and this is to the best of my recollection -- those that would 8 most likely have incorporated an adverse event of violence 9 towards another or an event of violence towards another, where 10 there may be that event embedded in it, in the event as 11 reported. 12 Q. What do you mean when you say the event embedded 13 in it? 14 A. Well, may I give you an example? 15 Q. Sure. 16 A. Antisocial personality. If someone struck 17 another person, a reporter, in reporting that to Lilly or in 18 our internal review mechanism, the event may have been 19 assigned to antisocial personality. It might not have fallen 20 into something that was readily captured for that particular 21 event, and at that time, as best I recall, the dictionaries 22 were somewhat limited in sort of capturing specifically that 23 type of event, although, as you might well expect, how one 24 defines violence can be very broad in terms of verbal, 25 nonverbal, et cetera. So I wanted to be sure that if such an 209 1 event occurred and it had been assigned to antisocial 2 personality, that we would capture that event. So from this 3 process we developed a list of approximately 20 events that we 4 then applied blindly to the clinical trial database to capture 5 any such events, and it was a very sort of exhaustive look 6 that led to that point, and from that we received specific 7 events of patients who may have had their event coded as 8 antisocial personality or some other such event. 9 Q. Let me make sure I understand this. You went 10 through the COSTART and ELECT dictionaries and gleaned from 11 these -- those dictionaries event terms that you felt were 12 related in some way to violent-aggressive behavior? 13 A. That could have incorporated violent or 14 aggressive behavior, and that was a process that involved more 15 than just myself. 16 Q. When I say you, I mean the people you were 17 working with. 18 A. Exactly. 19 Q. When I say you, I mean Lilly generally, the 20 people who were responsible. Okay? 21 A. Okay. 22 Q. So you went through -- just went through and 23 looked at event term to event term down the line to see what 24 was listed that you felt may have incorporated 25 violent-aggressive behavior, for instance, like you said, 210 1 antisocial personality and things of that nature? 2 A. We went event by event; correct. 3 Q. Then you ran those event terms in the DEN 4 database? 5 A. That's correct. 6 Q. And you pulled the 1639 printouts of those event 7 terms; correct? 8 A. That's correct. 9 Q. And then you went through and looked at those 10 1639s to see if somebody had actually committed harm or tried 11 to commit harm to somebody else? 12 A. That's correct. 13 Q. Okay. And of those cases where somebody tried 14 to commit harm to somebody else, what did you do? How did it 15 impact? How did the fact that they tried to commit harm to 16 somebody else impact on your analysis? 17 A. Then what we did is we made a decision as to 18 which of those many events that were initially sort of 19 screening type of events would seem to have been most likely 20 to capture an event. 21 Q. Where somebody committed harm towards somebody 22 else? 23 A. That's right. Where that sort of allegation had 24 been made. And at that point we had no idea if this would 25 have been verbal or nonverbal or just a perception, other than 211 1 it being reported, and so we took -- were able to identify 2 roughly 20 key event terms that we then applied blindly to the 3 database. 4 Q. Were these events where people -- let's say, for 5 instance, hostility was reported but the person who was 6 hostile had not made an actual aggressive act or move. Were 7 those considered, also? 8 A. Yes. 9 Q. Or was it just adverse events where somebody had 10 actually committed an injurious act to somebody else used? 11 A. Our efforts were to be as inclusive as possible, 12 and so where there was any possibility that an event term, 13 even though it had only identified in the initial screening 14 verbal aggression, we would have been -- we would have 15 included that in our effort to be inclusive. 16 Q. So it was verbal aggression, physical 17 aggression. Any other types of aggression towards others? 18 A. I suppose one could say perceived aggression; 19 that is where a reporter said he or she seemed hostile or 20 whatever in the postmarketing would have been something that 21 we would have looked at very careful, as well, so that we 22 wanted again to be as inclusive as possible. So there are 23 certainly -- in life in general there are specific occurrences 24 nonverbal hostility or aggression and there are specific 25 instances of verbal -- no, verbal hostility and aggression, 212 1 and then there would be what you and I might perceive as 2 hostile or aggressiveness that might not be in the eyes of 3 another, so it would be our perception. 4 Q. What is the aggression cluster of events? 5 A. As best I recall, those were those key events 6 that we identified that we would apply to the clinical trial 7 database. 8 Q. Okay. And that wasn't 17 events, though, 9 correct, or 20 events? 10 A. I don't recall. 11 Q. You narrowed down the number of events that you 12 decided were to be the aggression cluster of events; correct? 13 A. We narrowed those, but as best I recall, that 14 was still a rather sizable number of events. 15 MR. SMITH: Your Honor, at this time we would 16 offer Exhibit 115 which was Exhibit 1 to Doctor 17 Heiligenstein's deposition. 18 MR. MYERS: No objection. 19 JUDGE POTTER: Be admitted. 20 SHERIFF CECIL: (Hands document to jurors). 21 Q. Have you had a chance to review Exhibit 1, 22 Doctor? 23 A. I have. 24 Q. Do you recognize this exhibit? 25 A. I do. 213 1 Q. Tell me what it is. 2 A. These are events, as best I recall, that we 3 selected from the ELECT dictionary that would most likely have 4 incorporated verbal and nonverbal aggression. 5 Q. Intentional injury isn't on here, is it? 6 A. It's not. 7 Q. Is that one that you recall having used? 8 A. As best I recall, that was not a term that was 9 in the ELECT dictionary. 10 Q. How about COSTART? 11 A. As best I recall at the time this analysis was 12 done it was not in COSTART. 13 Q. Is it your testimony that that term has since 14 been incorporated into the COSTART dictionary? 15 A. I believe it has been. 16 Q. When was this analysis done? 17 A. This analysis was done -- I believe it was done 18 in 1989. 19 Q. Do you see any event terms that were pulled from 20 the ELECT dictionary that you recall that is not on this list? 21 A. None that I recall. 22 Q. Was this project done in 1989 before or after 23 the Wesbecker incident? 24 A. After Wesbecker. 25 Q. Do you recall this being done specifically in 214 1 response to the Wesbecker incident? 2 A. Yes. 3 Q. Which of these event terms were then used to 4 search the clinical database? 5 A. I can recall several, but I don't recall all. 6 Q. Okay. 7 A. The two that come to mind most immediately are 8 hostility and antisocial reaction. As I recall, there were 9 several others, as well. 10 Q. Is the cluster defined in your article? 11 A. It is. 12 Q. If I told you there was three events that are 13 listed in the article, would that surprise you, to make up the 14 cluster? 15 A. No. 16 Q. Why weren't all of these events run on the 17 clinical trial database? 18 A. Because in looking at these -- in pooling the 19 events from postmarketing there were not events that we could 20 identify where the individual, apart from, let's say, another 21 medical or neuropsychiatric illness, engaged in aggressive 22 verbal and nonverbal behaviors towards another. 23 Q. What do you mean when you say apart from another 24 psychiatric illness? 25 A. Well, for instance, an individual can experience 215 1 delirium as part of a metabolic illness, such as thyroid 2 disease and can be aggressive towards another, and that -- the 3 most likely explanation is the fact that the individual is 4 experiencing the delirium. 5 Q. Would that information be listed on the 1639, 6 that they were suffering from a thyroid disorder? 7 A. Oftentimes it was, yes. 8 Q. I guess I'm a little confused. Were all of 9 these people being treated with fluoxetine that you reviewed? 10 A. I don't know. 11 Q. Did you limit it to the treatment of depression? 12 A. Postmarketing? 13 Q. Your search; right. 14 A. The postmarketing search? 15 Q. Right. 16 A. No. 17 Q. Do you recall, was it broken down in any way 18 with regards to people who were suffering from depression that 19 suffered these adverse events as opposed to some other 20 indication? 21 A. I do not believe we split out where there was an 22 indication listed and where there wasn't an indication, and 23 within that indication, when an indication was noted, whether 24 we -- I don't recall that we did that. 25 Q. Okay. I want to get an understanding of how 216 1 this process actually worked. After you gleaned the event 2 terms from the ELECT dictionary, you then asked the systems 3 department to run a search on the DEN database for these ELECT 4 terms; correct? 5 A. That's correct. 6 Q. And how long did that search take, do you know? 7 A. I don't recall. 8 Q. Was it months? 9 A. No. 10 Q. Weeks? 11 A. I can't be sure. 12 Q. Okay. What was the result of that? Was that a 13 printout of the actual adverse events or was it the 1639s that 14 were turned over as a result of this search? 15 A. 1639s. 16 Q. Okay. So eventually your group got a stack of 17 1639s; correct? 18 A. That's correct. 19 Q. As a result of this search of all of these 20 adverse event terms? 21 A. That's correct. 22 Q. And then you physically went through those 23 1639s? 24 A. That's correct. 25 Q. Do you recall how many 1639s were you given? 217 1 A. I don't. 2 Q. Did everybody review all of the 1639s, everybody 3 in your group, or were they split up between you? 4 A. As best I recall, I reviewed every event. Where 5 there was any question about how to classify an event, then I 6 had a point person colleague who, as I recall, assisted me 7 with reaching a final judgment. 8 Q. Who was that? 9 A. Doctor Beasley. 10 Q. I want to know what happened to the original 11 stack of 1639s that the systems department came and gave to 12 you and said, "Here's the result of your inquiry regarding 13 these event terms." Did you review every single 1639? 14 A. I did. 15 Q. And what did you do in the process? Tell me 16 about that process. 17 A. I went through and reviewed each one and sought 18 to identify any event that involved, in a very inclusive way, 19 aggression towards another. 20 Q. What determined in your mind whether or not an 21 event included aggression toward another? 22 A. As best I recall, what I tried to do in that 23 process, in reading each of those carefully, was to ascribe 24 whether the event occurred in either a verbal or nonverbal 25 fashion directed towards another, and any attenuating or 218 1 additional information that would shed light on that specific 2 event. 3 Q. What other information? 4 A. Such as illnesses, other illnesses that could 5 possibly have precipitated the event. 6 Q. Where in the 1639 would the other illnesses be 7 listed? 8 A. As I recall, it could have been in -- it might 9 have been in the comments section. That's where the initial 10 report is recorded. Occasionally it was -- it may have been 11 mentioned in the section that deals with concomitant 12 medications. So it would be the text or concomitant 13 medications is where one might see that. 14 Q. Now, in every case where there appeared to be 15 another illness that could account for the person's behavior, 16 did you discount that adverse event? 17 A. I did not. 18 Q. What did you do? 19 A. I reviewed it with my colleague. 20 Q. Doctor Beasley? 21 A. Yes. 22 Q. Did he make the decision on whether or not to 23 include that adverse event or discount it because of another 24 illness? 25 A. We did that together so it was not -- if there 219 1 was any question in my mind, I visited that question to Doctor 2 Beasley, and then in collaboration we would say is this an 3 event that looks as if we have no other attenuating 4 circumstances that we can clearly identify based upon this 5 report. 6 Q. Other than reviewing the 1639s, did you do any 7 investigation on any individual adverse event? 8 A. Such as? 9 Q. Call the investigator or the person reporting 10 the adverse event? 11 A. Not that I recall. 12 Q. Why not? 13 A. Well, I'm not sure that we didn't, but I can't 14 recall. But if -- it may have been that the event would have 15 been rather straightforward, that there may have been 16 sufficient information, or that we felt in our clinical and 17 scientific judgment that we could make that decision. 18 Q. That another disease was more likely the cause 19 of the adverse event as opposed to the fluoxetine? 20 A. No. That the other disease might have been 21 associated with the event rather than causative, but that it 22 was more likely a component of that illness rather than the 23 illness for which fluoxetine is being prescribed. 24 Q. How about Joseph Wesbecker? Did you review his 25 1639 as part of this search? 220 1 A. That was the postmarketing event that led to 2 this exercise. 3 Q. Okay. Did you review his 1639? 4 A. Oh, yes. 5 Q. I guess what I'm getting confused at here is why 6 didn't you run all of these ELECT terms through the clinical 7 trial database? 8 A. One could have done that except it would not 9 have been scientifically correct. 10 Q. Why? 11 A. Because many of these events here reflect 12 disorders or events that bear no relationship, in our best 13 estimation, of a relationship to the use of fluoxetine. 14 Q. Do you understand what the word "related" means, 15 Doctor? 16 A. I think people use it differently. As I would 17 reflect upon your question, my thought would be that these 18 were events that were reported to us by, for the most part at 19 that point in time, prescribers, occasionally a family member, 20 very likely by our sales force who heard of a physician in his 21 office or her office say something to the effect of, "By the 22 way, I have this patient," and our sales force were instructed 23 to, as you well know, report everything they heard, so we had 24 collected a lot of data. It does not necessarily imply 25 relatedness or causality; it's a report. 221 1 Q. Would a physician doctor who prescribed 2 fluoxetine to somebody and knew that that person then took a 3 hit of LSD and then became psychotic, would they necessarily 4 report that to Lilly as an adverse event on fluoxetine? 5 A. They might. They might also mention in passing 6 to a sales-force person, though, who then, because of their 7 obligations would alert us to that. 8 Q. So if a doctor said to one of your sales-force 9 people, "God, I had Joe Blow on fluoxetine and then the 10 fool -- I had Joe Blow on fluoxetine and then the fool went 11 out and took a hit of acid and jumped off a building," they 12 would report that adverse event? They would report that 13 jumping off a building to you? 14 A. Yes, they would. 15 Q. Why? 16 A. Because they were instructed that if they heard 17 of any event occurring while a patient was being treated with 18 fluoxetine -- to the best of my knowledge, this is the 19 communication that was given to our sales-force personnel -- 20 they were to report that event to our DEN system, to our DEU 21 component. 22 Q. So if somebody was on fluoxetine and wasn't 23 having a problem with the drug but they walked out in the 24 street and got hit by a car, that accident would be reported 25 as an adverse event? 222 1 A. We have those reports in individuals who had 2 never even taken fluoxetine but where it had been prescribed 3 and not actually filled. 4 Q. Why do you report such events to the FDA? 5 Doesn't that skew the reporting system? 6 A. That's a judgment I can't make. What I can tell 7 you is that in my responsibilities and as I understood the 8 responsibilities of our sales force, is that we had to be as 9 diligent as possible in reporting events, and ours was not to 10 make a decision as to whether an event should be reported or 11 recorded or not but that it was to be done. 12 Q. Do you personally agree with reporting events of 13 people who were given a prescription of fluoxetine who never 14 took the drug and then were injured or killed by some sort of 15 accident as an adverse event on a drug? Do you agree with 16 that? 17 A. I don't know that it's my position to agree or 18 disagree because I'm not in the position of the federal 19 regulatory body, whether it would be here in the United 20 States, to determine how best to monitor the safety of a 21 compound. 22 Q. I'm asking for your personal opinion as to 23 psychiatrists, Doctor? 24 A. Well, prior to being in the industry I would 25 have said why; having been in the industry and having the 223 1 knowledge that I have now, it does help keep things in 2 perspective. 3 Q. Wasn't it easier for a company like Lilly to 4 point to a few hundred thousand reports of adverse events that 5 are unrelated to a drug and say, "Look, this guy wasn't even 6 on fluoxetine when he was hit by a car," and bury something 7 that may be related such as something like a Joseph Wesbecker 8 where he became more agitated and angry and mentally ill when 9 he was on the drug? 10 A. I would think that we would be more vulnerable 11 not to report, simply because there would be attorneys, 12 whatever, who would want to make the accusation that we did 13 not report events which were reported to us and that we were 14 trying to avoid the reporting requirement. 15 Q. I'm not talking about that were reported to you; 16 I'm talking about events like you described earlier where your 17 sales force was instructed to report any occurrence whatsoever 18 on fluoxetine that they'd heard about. 19 A. For all the years -- I'm speaking personally -- 20 that I've been in practice, I have thought that information 21 was power and that the more information you have, the more 22 helpful you can be. I think that's true in this situation, as 23 well. It seems at times, from a personal perspective, 24 tedious, but it's in the interest of safety, and in this 25 particular situation I find it helpful and important. 224 1 Q. That's assuming the information is adequate and 2 accurate, doesn't it? 3 A. That's a very broad question. I don't know how 4 I could answer that except to say that one can -- I think one 5 could argue what is adequate and what is inadequate to make 6 the necessary call. 7 Q. You said that, in your opinion, information is 8 power; correct? 9 A. That's correct. 10 Q. That's assuming that that information is 11 accurate information, does it not? 12 A. That's correct. 13 Q. If information is power, Doctor, why didn't you 14 run all of these adverse events in the clinical trial 15 database, at least to get information on how many of these 16 events were reported in the clinical trial database? 17 A. Because we wanted to -- what we didn't want to 18 be doing is running a large number of adverse events that 19 then, post facto, we would be saying, well, we shouldn't 20 really include this because it really doesn't pertain to the 21 possibility of, you know, the occurrence of the event with 22 fluoxetine but, rather, we wanted to do it as scientifically 23 correct as possible to sort of in some ways separate the wheat 24 from the chaff, so to speak. 25 Q. How can you know whether or not a particular 225 1 adverse event pertains to the use of fluoxetine if you hadn't 2 taken a look at that particular adverse event? 3 A. You mean relative to the analysis of the 4 clinical trial database? 5 Q. You didn't run all these adverse events in the 6 clinical trial database; correct? 7 A. Not that I recollect. 8 Q. And the reason you didn't run all of these was 9 because of what? 10 A. Because we developed from the initial review of 11 adverse events from postmarketing data what we felt was 12 scientifically, and to do it in a blinded fashion and to be I 13 think scientifically correct, we identified terms, the 14 aggression cluster that we felt would be most likely to 15 capture those events, and applied that to the database without 16 anyone knowing what the outcome would be. 17 Q. Would you agree with me, Doctor, as a 18 psychiatrist, that a number of these events represent risk 19 factors as to whether or not somebody is going to become 20 aggressive toward another person? 21 A. Some of these effects might very well reflect an 22 individual who would be at some vulnerability for that kind of 23 an expression. 24 Q. Okay. You mean the reason you picked these from 25 the ELECT dictionary is because you felt as a psychiatrist -- 226 1 you and your colleagues felt as psychiatrists that these were 2 the event terms that would most likely indicate some sort of 3 aggressive event or some sort of aggressive attitude on the 4 person's part; correct? 5 A. That's correct. 6 Q. Somebody could be feeling hostile towards others 7 and not verbalize that hostility; correct? 8 A. That's correct. 9 Q. So as risk factors, you're looking at these 10 various adverse-event terms to try to make a judgment or at 11 least a determination from to the postmarketing adverse events 12 as to whether or not people who were listed as suffering from 13 these adverse-event forms were in fact acting or verbalizing 14 aggression towards others; correct? 15 A. That's correct. 16 Q. My question is, then, how are you so sure that 17 people in the clinical trial database who were listed as 18 having these adverse events were not suffering from some sort 19 of increase or development of aggression just because they 20 didn't verbalize it or act on it? 21 A. In our best estimation and, again, addressing it 22 from a scientific perspective, we wanted to go into that 23 database with a cluster of events that we would then not have 24 to retrieve and peel away with other explanations such as the 25 occurrence of delirium with whatever or a manic episode, that 227 1 sort of thing. So it was the cleanest way, in our estimation, 2 to look at that database for those events of aggression 3 directed towards others. 4 Q. Wouldn't it have been more thorough to look at 5 every adverse event that occurred in the clinical trial 6 database that fell under one of these event terms to make a 7 determination, Number One, if that person was suffering either 8 the development of aggression or the increase in aggressive 9 feelings as opposed to just picking two or three adverse-event 10 terms and looking at those? 11 A. I think scientifically one would argue that the 12 way we proceeded in terms of an epidemiological study was the 13 most scientific. 14 Q. How many 1639s did you review from the initial 15 review of the DEN database with these ELECT terms? 16 A. I don't recall. 17 Q. More than 100? 18 A. From the DEN database, possibly, but I don't 19 recall. 20 Q. How long did it take you to complete your review 21 of the 1639s? 22 A. I don't recall. 23 Q. More than a week? 24 A. As best I recall, to expedite the process I was 25 given those in batches. 228 1 Q. Over what period of time? 2 A. I would you say a week, maybe two weeks. I just 3 can't be sure. 4 Q. What do you mean to expedite the process you 5 were given them in batches? 6 A. They would pool -- when they got a batch of 7 adverse events from any one of these terms, they would pool 8 and bring it to me so I could combine the review process. 9 Q. So you would look at the acute brain syndrome 10 adverse events at one time and then the hostility adverse 11 events at another time? 12 A. As best I recall, the events were organized in 13 that fashion. 14 Q. By event term? 15 A. By event term. 16 Q. Do you recall any crossover between 1639s? 17 A. Crossover meaning? 18 A. In other words, did you see a 1639 that fell 19 under the acute brain syndrome adverse-event group and the 20 same one falling in the hostility adverse-event group? 21 A. I don't recall that specifically, but it's 22 possible. 23 Q. Was there anything done to present that 24 crossover into various event-term groups? 25 A. No, we would not have done that. 229 1 Q. Do you recall from this list any adverse event 2 that wielded a greater number of 1639s than another? 3 A. I don't recall. 4 Q. I'm a little confused, Doctor. Let me see if I 5 understand what you guys did. You pulled the 1639s in which, 6 for instance, acute brain syndrome was listed as an adverse 7 event; correct? 8 A. That's correct. 9 Q. From the DEN? 10 A. That's correct. 11 Q. Okay. And then you reviewed those 1639s to see 12 if there was some other reason or something else that 13 contributed to or could have contributed to this person 14 suffering the adverse event of acute brain syndrome other than 15 fluoxetine -- other than the use of fluoxetine? 16 A. I don't recall that being the next step in the 17 process. 18 Q. Okay. 19 A. What I recall is that I first sought to 20 identifying with this specific 1639, this specific patient 21 report, whether there was behavior suggestive of aggressivity. 22 Q. So you looked at the acute -- let's just say 23 Patient A, okay? Patient A, you were given their 1639, okay? 24 A. Okay. 25 Q. And as an adverse event, acute brain syndrome is 230 1 listed on that 1639, okay? 2 A. Okay. Uh-huh. 3 Q. And then you look to see if there is something 4 in that report that indicates that Patient A was either 5 physically or verbally hostile towards other people, not 6 necessarily anybody in general or in particular; correct? 7 A. As best I recall. 8 Q. Now, if you determined that there was a verbal 9 or physical act indicating hostility towards others or 10 injurious intent towards others, what did you do with that 11 1639? 12 A. As best I recall, that event would have been 13 identified as an event for joint review. 14 Q. Okay. What did you do if Patient A did not, at 15 least as far as a 1639 was concerned, exhibit verbally or 16 physically injurious intent towards others? What was done 17 with that 1639? 18 A. With that particular 1639, it would have been 19 separated into a separate pile of like events. 20 Q. And what happened to that separate pile of like 21 events? What happened to those 1639s? 22 A. Physically? 23 Q. Yes. 24 A. I don't recall. 25 Q. What happened to them within this process? Were 231 1 they then considered in any way any further, or were they just 2 excluded from the group at that point? 3 A. As best I recall, they were excluded. 4 Q. Okay. So the first criteria for inclusion in 5 this was whether or not the 1639 from the DEN system indicated 6 that there was a visit -- a verbal or physical act of 7 aggression? 8 A. As best I recall, that would characterize the 9 initial step. 10 Q. Now, if it fell into that category where it 11 indicated in your judgment a verbal or physical act of 12 aggression, it was then reviewed by Doctor Beasley and 13 yourself? 14 A. As best I recall. 15 Q. Was this procedure written down anywhere? 16 A. I don't recall. 17 Q. Who determined this procedure? 18 A. There was a discussion that included several 19 individuals, some of whom I can recall, others that I cannot 20 recall. 21 Q. Okay. Who can you recall? 22 A. I can recall Doctor Beasley being a component of 23 that, and I recall Doctor Kotsanos being a component of that 24 early process. 25 Q. Anybody from the legal department? 232 1 A. No. 2 Q. Anybody from marketing? 3 A. Oh, no. 4 Q. Anybody from upper management? 5 A. No. 6 Q. How about Doctor Leigh Thompson? 7 A. He was not part of that discussion. 8 Q. How many other people were involved in that? 9 A. In that discussion? 10 Q. Yes. 11 A. There may have been several others. 12 Q. Was this one particular discussion where this 13 formula was devised? 14 A. I don't recall it being a formal meeting but, 15 rather, a process that began with the question, how does one 16 address the issue, the analysis of the clinical trial 17 database; and that was a process of discussion because we were 18 all in such close proximity, that is, Doctor Beasley, myself, 19 Doctor Kotsanos, possibly several others who had been 20 peripheral players in that initial discussion. We kind of had 21 these less formal types of discussions. 22 Q. Was it even limited to data from double-blind 23 control studies? 24 A. It was. 25 Q. Why were the other studies excluded? 233 1 A. As best I recollect, when one embarks upon such 2 a process, one needs to have some basis for making 3 comparisons, and the effort was to ensure that the data that 4 was reviewed would have been part of a double-blind controlled 5 study. 6 Q. Is it listed in your paper? 7 A. I believe it is. 8 Q. Prior to 1989, when this project was begun, did 9 you have any particular expertise in violent-aggressive 10 behavior in depressed patients? 11 A. Could you define what "particular expertise" 12 would mean? 13 Q. Did you focus in on that type of behavior in 14 depressed patients prior to 1989 in any of your work? 15 A. As a clinician, I was aware of individuals who 16 were depressed who would develop thoughts, ideations, at times 17 take action of wanting to harm themselves or others. My 18 expertise, given my clinical and academic experience, would 19 have been significant but not in terms of embarking on any 20 unique studies. As I mentioned earlier, I had not been 21 involved in research prior to coming to Lilly. 22 Q. And prior to starting this project in 1989, did 23 you have any particular interest in the phenomena of 24 violent-aggressive behavior in mentally ill patients in 25 general? 234 1 A. Directed towards others or self? 2 Q. Directed towards others for now. 3 A. I don't recall that I had a particular interest 4 in that area. I would have to say no. 5 Q. Okay. So the second step after your review of 6 the 1639s from the DEN database was to re-review the 1639s 7 that you felt indicated a verbal or physical act of aggression 8 or feeling of aggression with Doctor Beasley; correct? 9 A. As best I recall. 10 Q. And he reviewed those 1639s to make his own 11 determination as to whether or not he felt those 1639s 12 indicated aggression on behalf of the patient either verbally 13 or physically? 14 A. As best I recall. 15 Q. Do you recall him disagreeing with you on any 16 1639s that you felt were evidence of a verbal or a physical 17 act of aggression? 18 A. I don't recall that there were any 19 disagreements. 20 Q. Doctor, I think before lunch we had left off 21 where you had taken the 1639s from the DEN database that you 22 felt reflected aggressive or hostile behavior towards others, 23 injurious behavior towards others, either through a physical 24 or verbal act; is that your recollection? 25 A. That's my recollection. 235 1 Q. And those were taken to Doctor Beasley, and then 2 Doctor Beasley reviewed those 1639s to see if he agreed with 3 your determination as to whether these 1639s in fact reflected 4 hostility or injurious behavior towards others, either 5 verbally or physically; correct? 6 A. As best I recollect. I was very inclusive in 7 that sorting-out process, and so that he and I independently 8 then went through and looked at each of those and then melded 9 the process or the exercise in terms of these are the events 10 that most likely reflect other directed behavior, aggressive 11 behavior. 12 Q. But, I mean, did you go through them first and 13 make your initial determination and then give the group that 14 you had culled out to Doctor Beasley, or did Doctor Beasley 15 look at every single 1639 also? 16 A. Not that I recall. As I recall, I did some 17 sorting out in advance of that. 18 Q. So my understanding is clear, he looked at the 19 group that you initially reviewed and determined, where 20 indicative of injurious behavior towards others, either 21 physically or verbally? 22 A. He looked at that group, the all inclusive 23 group, and then from that process there was a sorting out, as 24 well. 25 Q. So did he cull out some that he felt or 236 1 disagreed with you about in your all-inclusive determination 2 were in fact related to evidence of verbal or physical 3 hostility towards others? 4 A. In my process I was inclusive to the extent that 5 anything that even I would not have included where someone 6 else might have judged that as a possibility, I included that 7 pile so that we both extracted from that initial separation. 8 As I recall, the events, that we then said do we agree that 9 this is one that captures certain events terms that we should 10 then apply to the clinical trial database. 11 Q. I know I'm probably getting confused, but let's 12 walk through this one step at a time. My understanding is -- 13 let's just use an example, the number 1,000 just for example 14 purpose. You were presented with 1,000 1639s that were culled 15 from the DEN database as a result of running these event terms 16 that are listed in Exhibit 1; correct? 17 A. That's correct. 18 Q. You went through and then, say, made a 19 determination that 200 of those did not, in your opinion -- 20 and again I'm just using 200 as an example -- did not in your 21 opinion show evidence of injurious behavior towards others, 22 either verbally or physically. 23 A. To the best of my recollection, there was a 24 group that I could very comfortably say this is not something 25 that should be considered in the next step of the process. 237 1 Q. So the ones that you culled out were then set 2 aside and you gave the ones that you felt were, in your 3 all-inclusive review, indicative of injurious behavior towards 4 others to Doctor Beasley to then review? 5 A. What I did was, where there would be any 6 question of the information available that there might be 7 some -- that they might be one of the final reports to be 8 selected from that process. So that number going from X 9 became Y, and then in the final effort between Doctor Beasley 10 and myself, became Z. 11 Q. Right. But I'm trying to take this step by 12 step, so please listen carefully to my question. Okay? The 13 group that you took from X to Y, Y is the group that you gave 14 to Doctor Beasley; you didn't give him the ones that you felt 15 were definitely not includable in the group that ended up 16 being Y? 17 A. As I recall, that's the way it proceeded. 18 Q. So you made an initial paring down, in effect, 19 of the number of 1639s before you gave them to Doctor Beasley? 20 A. To the best of my recollection, that's correct. 21 Q. Then Doctor Beasley reviewed the ones that you 22 had given him, the Group Y; right? 23 A. We each reviewed those again. He reviewed them 24 and I reviewed them again. 25 Q. And there was another paring down as a result of 238 1 your agreeing that a certain number of the Y group were not 2 includable as far as indicating injurious behavior towards 3 others; right? 4 A. That's correct. 5 Q. Do you recall how many 1639s were included in 6 the original group that you reviewed? 7 A. No, I do not. 8 Q. Do you recall -- can you give me a percentage 9 that were culled out in your initial review? 10 A. No, I can't. 11 Q. More than a third? 12 A. I can't be sure. 13 Q. Can you give me an estimate? 14 A. It would be speculation. No, I couldn't really. 15 Q. How about the group that resulted from you and 16 Doctor Beasley reviewing the 1639s together, the Group Z? Can 17 you give me a percentage of the total initial number of 1639s 18 that that was? 19 A. I can't. I don't recall what percentage. I 20 can't recall the denominator -- yes, the denominator that we 21 looked at initially and then narrowed it down to, so I 22 can't -- 23 Q. Less than half of the original? 24 A. I would expect. 25 Q. Yes. Less than half? 239 1 A. Well, to the best of my recollection it would be 2 less than half. 3 Q. Less than a quarter? 4 A. I can't say. I would think so. 5 Q. You would think so? You have to say yes or no. 6 You would think that it would be less than a quarter of the 7 original number? 8 A. To the best of my recollection, yes. 9 Q. Do you recall the number of 1639s that were left 10 after the entire review was done of this section of 1639s? 11 A. As best I recall -- and I believe that is in the 12 paper -- it was somewhere between 9 and 11. 13 Q. From the DEN review? 14 A. As I recall, uh-huh. 15 Q. After you and Doctor Beasley did your co-review 16 or your each individual review of those 1639s that you had 17 gleaned from the original group that you felt were indicative 18 of injurious behavior towards others, what happened with the 19 1639s that ended up being in these 9 or 11 final patients? 20 What did you do with those 1639s? 21 A. I don't know what happened to the original 22 1639s, but what we did with that is we extracted the 23 information and put them in what we call line listing, which 24 is patient identifier, age, sex, so and and so forth, with as 25 much information in a summary fashion as we could ascertain. 240 1 Q. Okay. Now, my original question was, did Doctor 2 Beasley review the 1639s from only the perspective of 3 determining whether or not the 1639 indicated injurious 4 behavior towards others, or did he also review it from the 5 perspective as to whether or not there was something else like 6 your example earlier, another disease process that may be 7 contributing to this person's condition, like delusion or 8 hostility? 9 A. As best I recollect, we agreed to the latter, 10 that once we began that process, we culled out, let's say, 11 individuals whose aggressivity may have very well been likely 12 or would most likely have been due to a condition that 13 developed related to another disease process. 14 Q. How about the disease process for which they 15 were being administered fluoxetine, for instance, depression? 16 Was that ever thought to be a cause of the aggressive 17 behavior? 18 A. Well, it was thought -- you know, I think in our 19 estimation a certain percentage of patients, and I can't quote 20 you a percentage, would be prone to self or other directed 21 aggressivity as part of the core illness, but we did not -- 22 that was not one of those eliminations. 23 Q. Okay. What other factors were taken into 24 consideration that possibly contributed to the person's 25 aggressivity. You already listed, for instance, another 241 1 disease process like thyroid, hyperthyroidism or something 2 along those lines. What other types of factors were taken 3 into consideration? 4 A. Apart from another illness? 5 Q. Right. 6 A. As best I recall, that was the only factor. 7 Q. Another disease process? 8 A. As best I recall. 9 Q. What about in, like, say, the obesity trials 10 that you reviewed. Was depression thought to be another 11 illness? 12 A. We didn't -- at that point we were not reviewing 13 trials. 14 Q. Okay. But certainly some people who you had 15 1639s on were being given fluoxetine for things such as 16 obesity or bulemia; right? 17 A. That's possible, yes. 18 Q. In those cases, if somebody was termed as, say, 19 suffering from depression or if it was thought that somebody 20 was suffering from depression in addition to bulemia, was 21 depression considered as another disease process, sort of like 22 hyperthyroidism, where that could be contributing to the 23 person becoming, for instance, hostile? 24 A. No, it was not. 25 Q. Okay. 242 1 A. So those would have been included. 2 MR. SMITH: Do you want me to continue, Your 3 Honor? 4 JUDGE POTTER: I was going to let Ms. Zettler 5 pick a spot. 6 MR. SMITH: Do you want me to continue, Ms. 7 Zettler? 8 MS. ZETTLER: You can stop, Paul. 9 JUDGE POTTER: Ladies and gentlemen, we're going 10 to take the evening recess. I'm going to remind you that you 11 have one exhibit there; it's No. 186. I tell you what. Why 12 don't you-all pass them over to the end there and give them to 13 one person and, that way, my sheriff will only have to collect 14 them from three of you at the end. Let me just tell you we're 15 doing this for -- two things -- to kind of keep you from 16 getting bogged down in paper is why we're collecting them back 17 up. And, also, I remind you that the time tomorrow morning is 18 9:00. 19 And again I'm going to give you my admonition. 20 Do not permit anyone to speak to or communicate with you on 21 any topic connected with the trial, and that includes the news 22 media or just friends or relatives or whatever. Do not 23 discuss it among yourselves and do not form or express 24 opinions about it. We'll stand in recess till 9:00. 25 (JURORS EXCUSED AT 5:05 P.M.; THE FOLLOWING 243 1 PROCEEDINGS OCCURRED IN CHAMBERS) 2 MR. SMITH: Two things. Tomorrow we have 3 scheduled the deposition of Doctor -- scheduled in-person 4 appearance of Doctor Lee Coleman, Mr. Wesbecker's 5 psychiatrist. We have begun the deposition of Doctor 6 Heiligenstein. Are we going to be required to complete that 7 before we put Doctor Coleman on? Should we call him and try 8 to delay him some? 9 JUDGE POTTER: It's -- certainly I have no 10 requirement that you do that. You know, it would be your 11 trial strategy. I can't imagine -- if you-all objected I 12 would sustain it. 13 MR. STOPHER: We don't have any problem with it. 14 15 JUDGE POTTER: It's just your trial strategy. 16 You might even consider reading an hour of it and then 17 bringing him in to break it up, because I gather their content 18 is pretty well separated; it's not like you need him before 19 Doctor Coleman. 20 MR. SMITH: The real thing that we need some 21 guidance from the Court on is Doctor Coleman has given his 22 deposition and both parties have talked to him since he's 23 given his deposition on an informal basis. It had been my 24 intent to call Doctor Coleman and to ask him his medical 25 opinions concerning his observations of Mr. Wesbecker up to 244 1 and including September 11th, 1989, which was the date ds 2 Doctor Coleman last saw Mr. Wesbecker. Neither party has 3 designated Doctor Coleman as an expert on the issue of whether 4 or not Mr. Wesbecker committed the act of September 14th as a 5 result of his ingestion of Prozac, and we don't intend to 6 inquire of that. We want an instruction, motion in limine 7 now, that they not be allowed to inquire of that by virtue of 8 the fact that they have not designated him as an expert 9 witness, not issued a designation of what his opinion is on 10 that issue. 11 MR. STOPHER: Judge, we did not list him as an 12 expert witness because he is a co-defendant technically still 13 in this case; that judgment has not been made final and 14 appealable; it's still interlocutory but, more importantly, he 15 is also a defendant in an ongoing case involving the Estate of 16 Joseph Wesbecker against himself and Eli Lilly and Company. 17 So it would have been inappropriate for us, I believe, to have 18 hired him as an expert witness, which we did not do. But the 19 fact of the matter is, Your Honor, that he is entitled to give 20 medical opinions, if he has them, as to the cause of the 21 violent acts of his patient three days after he saw him, and 22 we would very much want to ask that question. It's been asked 23 before of him, I'm sure. 24 JUDGE POTTER: In his depositions? 25 MR. STOPHER: Yes, sir. And we would most 245 1 definitely want to hear his medical opinions as to the cause 2 of the acts of his patient three days after he saw him. So 3 the fact that we did not designate him as an expert witness we 4 don't think should preclude him as a psychiatrist, and indeed 5 the treating psychiatrist, from giving his medical opinions 6 regarding the issues of causation, assuming that he has them. 7 MR. SMITH: Our point is, he's not been 8 designated by them to render such an opinion and that they 9 should not be able to inquire of his opinion, especially if we 10 don't raise the issue. 11 JUDGE POTTER: Well, in some respects it's 12 already been raised because his medical record's come in and 13 they've got "Prozac cause, question mark" or whatever that 14 medical record says. 15 MR. SMITH: The point is that speaks to the 16 cause of his condition on September 11th, three days before 17 this. The issue as to whether or not it caused his conduct on 18 September 14th is something separate and apart that all the 19 parties have done discovery on, hired separate causation 20 experts on to render expert opinions, taking into account 21 things including Doctor Coleman's records but things much more 22 inclusive than Doctor Coleman's records. They've hired 23 experts on causation; we've hired experts on causation. 24 They've not designated Doctor Coleman as an expert witness on 25 causation, they ought not to be able to inquire as to what his 246 1 opinion is on September 14th. 2 JUDGE POTTER: All right. If we're down to 3 whether or not he can say what caused him to cry and break 4 down in his office and hallucinate on the 11th versus what 5 caused him to shoot somebody on the 14th, if that's the split, 6 you know, I really don't think it's much difference, but I 7 would say don't ask him about the 14th. Everybody fight about 8 what made the guy degenerate on the 11th. The jury's going to 9 sit there and say if he fell apart because of Prozac on the 10 11th, that's what caused him to shoot on the 14th; if Prozac 11 didn't have anything to do with him falling apart on the 11th, 12 it didn't have anything to do with him falling apart on the 13 14th. If that's the distinction it's, to me, a distinction -- 14 a difference without a distinction or a distinction without a 15 difference, but maybe that is the thing. He can tell why he 16 thought he was bad on the 11th and whether he thought Prozac 17 was causing him to hallucinate and all that sort of stuff. 18 MR. STOPHER: Judge, he's the only man of all 19 these experts that treated and saw Joe Wesbecker. And if he 20 can express a medical opinion as to whether or not his 21 condition on the 11th of September caused his homicidal and 22 assaultive acts three days later, I think the jury is entitled 23 to hear that position. He is in a unique position and this 24 issue has come out. They want to suggest that the treating 25 physician's notes about deterioration on the 11th and hold 247 1 that off, draw down a curtain and don't let the jury hear the 2 treating physician's opinion as to whether or not that 3 condition made him homicidal on the 14th, and I think they're 4 entitled to hear that. 5 JUDGE POTTER: Maybe I'm just naive or simple, 6 but he's certainly not going to say that Prozac caused him to 7 go delusional or whatever he was on the 11th but had nothing 8 to do with what happened on the 14th. 9 MR. SMITH: Oh, yes. 10 MR. STOPHER: I think he's entitled to say that, 11 if that is his medical opinion, that the condition that he was 12 in on the 11th did not make him homicidal. As the treating 13 physician, he ought to be entitled to say that. 14 JUDGE POTTER: He's going to say that? 15 MR. STOPHER: I'm assuming that. And I think 16 the jury is entitled to hear what the treating physician is 17 going to say. 18 MR. FREEMAN: It's one thing to be anxious and 19 agitated, and it's quite another thing to be anxious and 20 agitated and then go out and commit a homicidal act. 21 MR. SMITH: My point is that I ought to be able 22 to take him up and through what he observed his psychiatric 23 state was on September 11th, but nobody has designated this 24 man as a causation expert for what his conduct was on 25 September 14th. They can't and I can't ask him why did he do 248 1 it on September 14th. I ought to be able to ask him, though, 2 what did he attribute his symptoms to on September 11th. 3 JUDGE POTTER: The testimony that is anticipated 4 is that he's going to say Prozac caused him to remember this 5 thing about the foreman performing sodomy on him but didn't 6 cause him to go in and shoot the foreman? 7 MR. STOPHER: He's going to say, if I understand 8 correctly -- we both talked to him -- that it is a possibility 9 on the 11th but that -- it is a possibility that Prozac 10 contributed to his condition on the 11th of agitation and 11 anxiety, but that it is his medical opinion that anxiety and 12 agitation did not cause his acts on September the 14th, 1989. 13 Now, going back to Mr. Smith's objection, his 14 objection is based on the fact that neither party identified 15 him as an expert. Now, we're only entitled to identify as 16 experts people that we've employed. He is a party. 17 JUDGE POTTER: I don't know about that, but 18 that's... When was Doctor Coleman's deposition taken? 19 MR. STOPHER: It's been taken on several 20 occasions, Judge. 21 MR. SMITH: It's been taken on three occasions, 22 and the last one being a year ago, wasn't it? 23 MR. STOPHER: I think it was spring of '93. 24 JUDGE POTTER: When did he get out of this 25 lawsuit? 249 1 MR. STOPHER: It was after that, Judge. 2 JUDGE POTTER: So all of his depositions were 3 taken prior to his getting out of the lawsuit? 4 MR. STOPHER: That's correct. 5 MR. SMITH: You see, this is an issue now 6 because, frankly, I suspect -- well, it doesn't make any 7 difference what I suspect. The point is, is that the man 8 ought to be -- he hasn't been hired to do an investigation, he 9 doesn't know any of the circumstances that might have occurred 10 between September 11th and 14th. His opinion ought to be 11 limited to his condition up and through September 11th when he 12 walked out that psychiatrist's door the last time. 13 MR. STOPHER: Well, judge, with regard to this 14 issue, the whole case is about causation. And of all the 15 people that are involved in this, we've heard testimony from 16 people so far that, well, he would have been the last person I 17 would have thought would do it or he would have been somebody 18 that I thought would do it; that sort of testimony came in, 19 but I think the jury is entitled to hear what this treating 20 doctor's opinion is as to whether or not his medical condition 21 just three days before in any way caused or contributed to 22 cause what he did on the 14th. No one else is in a position 23 to be able to do that based on firsthand observation of the 24 person involved. 25 JUDGE POTTER: See, I've always been kind of 250 1 under the impression that Doctor Coleman was kind of like a 2 homeowner; no matter how little they know or how unqualified 3 they are, in a condemnation the homeowner gets to come in and 4 say I think my house is worth whatever's it's worth. It's 5 kind of a tradition. Here's the guy that's treating him, and 6 I kind of assumed he was going to come in and be able to 7 express an opinion. It never occurred to me that he would 8 split his opinion between the 14th and the 11th. I mean, I 9 kind of assumed that -- I hadn't read his depositions. 10 I do think an expert does not have to be a paid 11 expert. I mean, it can be anybody. Mr. Smith I guess could 12 designate the people from Lilly as experts if he wanted to. 13 But Doctor Coleman, since you-all have taken his deposition, 14 it doesn't catch anybody by surprise. He was a party to the 15 lawsuit, is still a party to the lawsuit. He is the treating 16 physician and, in my mind, Mr. Smith, and to the jury's mind 17 -- maybe they're more sophisticated than I am -- I assume 18 that, you know, that you've put in issue that Doctor Coleman 19 has expressed an opinion that this deterioration was caused by 20 Prozac, therefore the shooting was caused by Prozac. It never 21 occurred to me that somebody could dance a tightrope in one 22 and not the other. 23 MR. SMITH: I think he got visited by various 24 and sundry people that gave him information that's inaccurate. 25 Regardless of that, he's got to be designated. If they want 251 1 to designate -- if they want him to testify as to causation, 2 they've got to designate him. They've spent thousands of 3 dollars hiring people. That's something that you make an 4 independent analysis. All Doctor Coleman can testify to is 5 his medical condition the last time he saw him. If he 6 testifies to anything else, he's really opening himself up for 7 liability. Don't you have to designate experts here? 8 JUDGE POTTER: Well, there comes a question of 9 whether Doctor Coleman is an expert or a fact witness. I 10 mean, a fact -- 11 MR. SMITH: If he's a fact witness he certainly 12 can't give his opinion. 13 JUDGE POTTER: No. An expert, I mean, we could 14 go get the definitions, but, to me, an expert is somebody that 15 has never really touched, felt, smelled what's going on. He 16 comes in, you give him some stuff and he gives you an opinion. 17 Doctor Coleman is the person that came in, touched, smelled, 18 felt this guy. He is testifying based on his own personal 19 experience, you know, not looking at skid marks and saying the 20 car was going 60; he was standing on the street corner and saw 21 the guy go by. I've always considered him kind of a fact 22 witness. The distinction between a fact witness of what his 23 condition was on the 11th versus the fact witness of what his 24 condition is on the 14th, I'm going to let him testify, 25 partially because he's a fact witness, partially because -- 252 1 primarily because I guess he's a fact witness, primarily 2 because he's been in this lawsuit. Everybody's taken his 3 deposition so what he's going to say, if it is a surprise, 4 you-all won't be surprised. 5 That brings up an issue. Again, I hate to 6 anticipate something but how -- does anyone plan to bring up 7 the fact that he was a defendant in this lawsuit or that he is 8 still a defendant in this lawsuit. 9 MR. SMITH: You betcha. You betcha. 10 Absolutely. I'm going to blast him. 11 JUDGE POTTER: Let's hear what you're going to 12 blast him with. 13 MR. SMITH: I'm going to tell that jury he got 14 sued -- didn't you get sued; didn't this Judge grant you a 15 summary judgment; isn't that summary judgment still on appeal; 16 don't these people still have a claim against you; hasn't 17 Lilly offered to indemnify you; hasn't Lilly told you they'll 18 pay your cost of appeal, et cetera, et cetera. 19 JUDGE POTTER: Do you have a good-faith basis to 20 believe he's going to answer affirmatively on it? 21 MR. SMITH: Affirmative on every one. 22 MR. STOPHER: Judge, that's not admissible in a 23 case in which he's been dismissed on procedural grounds. That 24 was a dismissal, if I understand the order correctly, that was 25 based on a statute. The dismissal is admissible, and he can 253 1 be cross-examined on it only if it is based on the merits, and 2 in this case it was a procedural dismissal. 3 JUDGE POTTER: Oh. Oh. Oh. I think the 4 psychiatric -- Mr. Bubalo would like to think he got it on the 5 merits that this guy had no duty because of the statute. I 6 mean, these people see it as a procedural statute that was 7 passed to protect them, but, I mean, it's a dismissal on the 8 merits, I mean, at least in my interpretation of the 9 legislature, said that he had no duty to do anything because, 10 you know, the proper foundation -- not foundation but proper 11 prerequisites hadn't and in my estimation could never be 12 shown. 13 MR. STOPHER: Well, I certainly think it's 14 inappropriate to cross-examine a witness based upon a court 15 ruling that I doubt very seriously that he even understands. 16 But if he wants to undertake that risk of doing that and 17 introducing that, I think it's inappropriate and I object for 18 all those reasons but... 19 JUDGE POTTER: Well, let me -- 20 MR. STOPHER: I don't represent Doctor Coleman, 21 and I think perhaps his attorney ought to be given some 22 advanced notice that Mr. Smith wants to do that, and he may 23 want to make his own motion. I can't purport to represent him 24 in this kind of a thing. 25 JUDGE POTTER: When he gave his deposition -- 254 1 and having granted the man a summary judgment it sounds 2 terrible to say I haven't read his deposition, or if I did 3 read it I don't remember it, but the issue really wasn't his 4 deposition; the issue was what you-all were going to be able 5 to pull forward, so it was the absence, not what was there. 6 And everyone told me that he denied in the deposition there 7 was nothing in the records and that wasn't in dispute. That 8 confession over with, in your conversations with him since his 9 deposition and since his dismissal has he changed direction or 10 was it always a split between the 11th and the 14th? 11 MR. SMITH: He said I believe in his deposition 12 that he felt like in all probability the deterioration on the 13 11th was a result of the Prozac but that he felt it didn't 14 have anything to do with the murder on the 14th. He said that 15 in his deposition, I think. Is that accurate? 16 MR. STOPHER: That is correct. That is correct. 17 MR. SMITH: But he's going to testify tomorrow 18 that -- it's like he read Mr. Stopher's opening argument -- 19 this was a premediated, planned homicide. He was mad at the 20 people at Standard Gravure; he had been planning on doing 21 this; and he went out and blew them away, and he deceived me. 22 MR. STOPHER: Well, I think Mr. Smith can 23 cross-examine him, but going back, Judge, to the issue of 24 whether or not he's entitled to beat him up with the fact that 25 he's been sued and that the Court gave him a summary judgment 255 1 I think that's inappropriate, and I guess the thing to do is 2 to notify his attorneys because -- 3 JUDGE POTTER: And he will answer in the 4 positive to whatever kind of agreement there is. 5 MR. STOPHER: There's no agreement. 6 MR. SMITH: There's no agreement. It's been 7 represented to him orally. 8 MR. STOPHER: Lilly wrote a letter to every 9 physician saying if you get sued we want to agree to indemnify 10 you. And in this case that was never, ever done. It was 11 never accepted. 12 MR. SMITH: He's told me he was visited from the 13 people from Lilly and they told him they'll take care of it. 14 MR. STOPHER: And it was never accepted. It was 15 never done. He's testified to that numerous times. 16 JUDGE POTTER: Let me get this straight. What 17 you're talking about is the letter that went out to 75,000 18 doctors around the country? 19 MR. STOPHER: Right. That's my understanding. 20 MR. SMITH: I'm saying something different than 21 that. 22 JUDGE POTTER: I think maybe, Mr. Smith, they 23 have made a motion in limine to keep out evidence that, first 24 of all, that he was dismissed from a lawsuit; that, I think I 25 could handle without a hearing. But the evidence that Lilly 256 1 has agreed to indemnify him if he has any problems here, that 2 did not come out in his deposition; is that right? 3 MR. SMITH: No. 4 JUDGE POTTER: I think maybe what we need to do 5 is have a quick voir dire hearing and let you ask him those 6 questions out of the hearing of the jury to see what he's 7 going to say or exactly see what we're talking about, because, 8 I mean, to me, that's... Well, let's do this. What kind 9 of -- do you have him under subpoena or is that what you've 10 got? 11 MR. SMITH: He's agreed to come here at 9:00. 12 JUDGE POTTER: Why don't we go in there and see 13 if we can get him and Mr. Bubalo over here at 8:00 so that 14 whatever needs to be thrashed out can be thrashed out. 15 MR. SMITH: I don't think we can get Bubalo; we 16 can try, certainly. But he left us a card of some other 17 lawyer in his office. 18 JUDGE POTTER: That's fine. Just so that the -- 19 I don't even care if the lawyer comes, but what I don't want 20 to do is get over here and Doctor Coleman say, "Wait, I need 21 my lawyer," and we've got to wait three hours to track 22 somebody down. I mean, it's just whose name did he -- is Mr. 23 Bubalo out of town or he's just flipped the pass off? 24 MR. SMITH: I just got the impression since he 25 had already -- 257 1 MR. STOPHER: He's in trial. He started a trial 2 today. 3 JUDGE POTTER: After the indemnity agreement he 4 doesn't care. Did he give you the card of somebody in Mr. 5 Stopher's office. 6 MR. STOPHER: It's Tracy Prewitt, who's been on 7 most of these depositions of plaintiffs and everybody else. 8 MR. FOLEY: That's who it is? 9 MR. STOPHER: You know her. She's been in a 10 hundred depositions in this case. 11 JUDGE POTTER: Mr. Foley, will you play a part 12 in this and track down Ms. Prewitt? Could she be available in 13 case. It's just my concern that the Doctor may want her here, 14 and we don't want to have to waste two hours tracking somebody 15 down. 16 MR. FOLEY: And you'd like the Doctor here at 17 eight? 18 JUDGE POTTER: Yeah. Because that way Mr. Smith 19 can ask him his questions and we'll know exactly what we're 20 dealing with. 21 MS. ZETTLER: Judge, we have two other quick 22 things. We need to finish up the objections on Heiligenstein, 23 so can we do that tonight in case something happens and we 24 need to do it before lunch or come in early, at 7:30 tomorrow. 25 JUDGE POTTER: Can we do it at 7:30? 258 1 MS. ZETTLER: Also, we're going to need a list 2 of witnesses from them. 3 JUDGE POTTER: That's right. 4 MS. ZETTLER: Probably first thing in the 5 morning. 6 MR. STOPHER: When are you going to be done, 7 Paul? 8 JUDGE POTTER: Either tomorrow afternoon or 9 Thursday morning. 10 MR. STOPHER: I'll bring a list in the morning. 11 JUDGE POTTER: There's a motion from them to 12 shorten the time to answer interrogatories. 13 MR. STOPHER: We'd like to respond to that in 14 writing. What is today? We'll respond by Friday if that's 15 all right with you. 16 JUDGE POTTER: Okay. I don't want to sound 17 like -- well, it does sound like I've prejudged it, but you 18 ought to get people working on the answers so that if you 19 don't get your motion you've got a head start on it. I didn't 20 look at all the questions, but some of it looks like something 21 you can mail off to people in Indianapolis and have them -- 22 you know, your thing may be an objection, but if it is, it 23 sounds like an objection that can be conjured up in 10 days as 24 opposed to 30. 25 MR. STOPHER: We definitely want to object. 259 1 There's a lot of law on this topic here. 2 JUDGE POTTER: No. No. The motion is about the 3 time. 4 MR. STOPHER: Oh, about the time. Oh, okay. 5 JUDGE POTTER: It's whether we can cut it to ten 6 days and for you-all to answer or object. 7 MR. STOPHER: No. What I'm talking about to you 8 is to object to the interrogatories. 9 JUDGE POTTER: So what I think you're saying is 10 I can go ahead and sign the ten-day order because you're going 11 to go ahead and plan to get your objections in by this Friday? 12 MR. STOPHER: Absolutely correct. I want to 13 address the merits of whether or not it's appropriate to 14 introduce that or discover it. 15 JUDGE POTTER: Do pick through it. Some of them 16 you may answer and some of them you may object to. I haven't 17 read them all, but it did look like the kind of stuff that 18 could be gathered fairly quickly. 19 MR. SMITH: So I know where we stand -- 20 JUDGE POTTER: Ms. Zettler needs to be here at 21 7:30 and Mr. Myers needs to be here at 7:30. And if you can, 22 get Doctor Coleman here at eight, and Mr. Foley's going to 23 tell his lawyer that he's going to be here at eight and have 24 his lawyer where we can get them on the telephone if Doctor 25 Coleman wants his lawyer here, but I'm not going to -- 260 1 MR. SMITH: We need to contact -- why don't you 2 go do that now, Irv, so you can catch her before she leaves 3 because, I mean, we can't contact Doctor Coleman directly. 4 MR. FOLEY: I'll call her right now. 5 MR. STOPHER: I'll go with you. I know their 6 phone number. 7 MR. SMITH: The Court is going to hear -- let me 8 see if I understand because I've got a plan on how to handle 9 this guy, obviously. Is the Court going to allow them to ask 10 him the question of whether or not whether he has an opinion 11 concerning the causal acts of September 14th, 1989, the day of 12 the shooting and what it is? Is that what the Court's going 13 to do? 14 JUDGE POTTER: Uh-huh. Uh-huh. Uh-huh. 15 MR. SMITH: All right. The issue that's going 16 to be decided now is -- 17 JUDGE POTTER: First of all, how we handle "Mr. 18 Wesbecker's estate still has a pending lawsuit against you, 19 yes, that's fine; Doctor, you used to be a defendant in this 20 lawsuit and you've been dismissed out, yes, I don't have a -- 21 just exactly how that's handled. 22 MR. SMITH: That's what you're going to decide 23 in the morning? 24 JUDGE POTTER: Yeah. And then also how he will 25 answer the question, Doctor, has Lilly promised to indemnify 261 1 you; if this lawsuit works out badly they'll pick up the tab 2 or whatever questions you intend to ask him about that. If he 3 says no, nothing like that's gone on, that's one way; if he 4 says yes, then that's another way. But I just think it's 5 something that I want to know ahead of time what it's going to 6 be before you ask it in front of a jury. 7 MS. ZETTLER: Your Honor, we will need 8 objections and whatever else Mr. Myers wants to do with the 9 Beasley deposition tomorrow morning. 10 MR. MYERS: Well, we were just given Doctor 11 Beasley's designation Sunday afternoon. We received Doctor 12 Heiligenstein's in installments on three, Saturday and Monday 13 and moved heaven and earth to have them here this morning. 14 But under the Court's order, we're getting after it. 15 MS. ZETTLER: First of all, he got part of 16 Beasley on Saturday. 17 JUDGE POTTER: Okay. You've got Doctor Coleman, 18 Heiligenstein, Beasley. 19 MR. SMITH: That will probably be all we've got. 20 MR. MYERS: Ms. Zettler told me no more 21 designations; I'd like a ruling on that. 22 JUDGE POTTER: I thought I heard you say another 23 one. 24 MR. MYERS: No. They're only, Judge, only 25 about -- I'm doing a little guesstimating. They're about a 262 1 quarter of the way through the Heiligenstein's designations. 2 MS. ZETTLER: There's not that much on the 3 second deposition. 4 JUDGE POTTER: We'll do Heiligenstein tomorrow 5 morning. If we have to quit a little early... I think Doctor 6 Coleman may take awhile; who knows. 7 MR. SMITH: May not. 8 JUDGE POTTER: Well, they may take him awhile. 9 Let me put it this way. If this is what you've got left and 10 you-all have, you know, dealt in good faith, we'll finish 11 Heiligenstein tomorrow, and if we don't get to Beasley we'll 12 take it off and get Beasley in Thursday morning. 13 MR. STOPHER: Judge, we were unable to get them 14 on the phone. They're going to call us back, both Irv and 15 myself, on a conference call in a little bit, and as soon as 16 we find out, what do you want us to do? 17 JUDGE POTTER: Just ask the Doctor to be here at 18 8:00 and tell the lawyer it's up to her to come if she wants 19 to. And if she doesn't, but do be available in case he gets 20 cold feet or gets nervous or something. 21 MR. SMITH: Could I ask the Court even though 22 the Court has indicated what his rulings would be on the 23 causation question to think about it. 24 JUDGE POTTER: Didn't I say once, Mr. Smith, 25 that I'm always in doubt? 263 1 MS. ZETTLER: Can we get you some case law. 2 JUDGE POTTER: Sure. I'll read anything you 3 want to give me tomorrow morning. 4 (PROCEEDINGS TERMINATED THIS DATE AT 5:40 P.M.) 5 * * * 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 264 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 265 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25