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 THURSDAY, OCTOBER 13, 1994 15 VOLUME XIV 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 WITNESS: DOCTOR_HANS_WEBER - By Video Deposition (Cont'd) _______ ______ ____ _____ 5 Examination by Mr. Smith................................. 5 6 WITNESS: DOCTOR_W._LEIGH_THOMPSON _______ ______ __ _____ ________ 7 Examination by Mr. Smith................................. 12 8 * * * 9 Reporter's Certificate...................................185 10 11 * * * 12 13 14 15 16 17 18 19 20 21 22 23 24 25 3 1 2 A_P_P_E_A_R_A_N_C_E_S _ _ _ _ _ _ _ _ _ _ _ 3 4 FOR THE PLAINTIFFS: 5 PAUL L. SMITH Suite 745 6 Campbell Center II 8150 North Central Expressway 7 Dallas, Texas 75206 8 NANCY ZETTLER 1405 West Norwell Lane 9 Schaumburg, Illinois 60193 10 IRVIN D. FOLEY Rubin, Hays & Foley 11 300 South, First Trust Centre Louisville, Kentucky 40202 12 13 FOR THE DEFENDANT: 14 EDWARD H. STOPHER Boehl, Stopher & Graves 15 2300 Providian Center Louisville, Kentucky 40202 16 JOE C. FREEMAN, JR. 17 LAWRENCE J. MYERS Freeman & Hawkins 18 4000 One Peachtree Center 303 Peachtree Street, N.E. 19 Atlanta, Georgia 30308 20 ALSO PRESENT: 21 DR. W. LEIGH THOMPSON 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 Thursday, October 13, 1994, at approximately 9:10 A.M., said 5 proceedings occurred as follows: 6 7 * * * 8 9 SHERIFF CECIL: The jury is now entering. All 10 jurors are present. Court is now in session. 11 JUDGE POTTER: Okay. Please be seated. Did any 12 of you-all have any problems with the admonition the last 13 couple of days? How about you, Ms. Jones; have you had any? 14 JUROR JONES: No. 15 JUDGE POTTER: Ms. Shelly, you mentioned to my 16 sheriff that your, I guess, maiden name is similar to -- I 17 said Shelly -- Shelby. I'm sorry. Selby. I still can't get 18 it right. You mentioned that your maiden name is the same as 19 one of the names of one of the German witnesses. That's not 20 going to cause any problem for you, is it? Is that going to 21 cause you any problem? 22 JUROR SELBY: No, not at all. 23 JUDGE POTTER: Thank you. I'm sure you wanted 24 me to know and I wanted to acknowledge that I knew. 25 Mr. Higgs, you indicated that you wanted to say 5 1 something to the lawyers or to me? 2 JUROR HIGGS: Yes, sir. 3 JUDGE POTTER: Okay. Do you want to step up 4 here. 5 (BENCH DISCUSSION) 6 JUDGE POTTER: Mr. Higgs, I need for you to be 7 sure and speak into this, because the Court Reporter is 8 picking it up through the microphone. 9 JUROR HIGGS: I just wanted to let you-all know 10 that I delivered last night to Indianapolis to M. L. Moss, 11 which is right around the corner from Lilly, and I've got nine 12 more of them to run by Monday morning, so I just wanted to 13 make sure you knew. 14 JUDGE POTTER: Okay. That's all right. Thank 15 you. 16 (BENCH DISCUSSION CONCLUDED) 17 JUDGE POTTER: Mr. Smith, you want to continue 18 with the deposition of Mr. Weber? 19 MR. SMITH: Please, Your Honor. At this time, 20 Your Honor, we have Weber Exhibit 5, which is Plaintiffs' 21 Exhibit 65 to be offered. 22 JUDGE POTTER: Be admitted. 23 (BENCH DISCUSSION) 24 MR. MYERS: I just want the Court to be clear 25 that this is being admitted over my earlier objection as to 6 1 the testimony on this subject, which was also overruled. 2 JUDGE POTTER: Okay. 3 (BENCH DISCUSSION CONCLUDED) 4 JUDGE POTTER: Go ahead and give it to my 5 sheriff. 6 SHERIFF CECIL: (Hands exhibit to jurors). 7 (VIDEO DEPOSITION OF DOCTOR WEBER CONTINUES) 8 MR. SMITH: If I can, Your Honor, we have 9 Exhibit 6, which is Plaintiffs' Exhibit 66. 10 (BENCH DISCUSSION) 11 MR. MYERS: Judge, just for the record, I want 12 to renew our objection to this exhibit and the testimony on 13 the previous grounds that you overruled but as relate to the 14 testimony, just for the record. 15 JUDGE POTTER: I'm going to let the document in 16 over Lilly's objection. 17 MR. MYERS: Yes, sir. 18 (BENCH DISCUSSION CONCLUDED) 19 SHERIFF CECIL: (Hands exhibit to jurors). 20 (VIDEO DEPOSITION OF DOCTOR WEBER CONTINUES) 21 MR. SMITH: At this time, Your Honor, we have 22 Exhibit 7. 23 JUDGE POTTER: Sixty-seven? 24 MR. SMITH: Plaintiffs' 67, which is Weber 7. 25 (BENCH DISCUSSION) 7 1 MR. MYERS: Judge, I object to this exhibit and 2 to Exhibit 8, which it goes along with, so I won't get up 3 again, on the same grounds due to earlier testimony. 4 JUDGE POTTER: Okay. 5 SHERIFF CECIL: (Hands exhibit to jurors). 6 (VIDEO DEPOSITION OF DOCTOR WEBER CONTINUES) 7 MR. SMITH: Your Honor, he's reading from 8 Exhibit 8, Plaintiffs' Exhibit 68. I didn't jump quick enough 9 to stop it. 10 JUDGE POTTER: Okay. 11 SHERIFF CECIL: (Hands exhibit to jurors). 12 (VIDEO DEPOSITION OF DOCTOR WEBER CONTINUES) 13 MR. SMITH: Your Honor, we may have 30 to 35 14 minutes left on this tape. 15 JUDGE POTTER: I thought you said it was an hour 16 and 20 minutes when you started. 17 MR. SMITH: And it was, but we've been 18 interrupting it. 19 MS. ZETTLER: Probably about a half an hour. 20 JUDGE POTTER: Why don't we stand up and -- 21 well, let -- we'll go ahead and take a morning recess at this 22 time. I'm going to ask the people that are spectators to wait 23 just a second till after the jury's left because I want to say 24 something to you-all. 25 Ladies and gentlemen of the jury, remember my 8 1 admonition. Do not allow anybody to talk to you about this 2 case or any topic connected with it. Do not discuss it among 3 yourselves and do not form or express opinions about it. 4 We'll take a 15-minute recess. 5 (JURORS EXCUSED) 6 JUDGE POTTER: Let me just mention one thing. 7 As you-all have undoubtedly discovered, the elevator for this 8 building is not built to handle more than very few people. 9 When this building was built, the fourth floor contained three 10 judges, and there was just one or two people going up and down 11 at the time. It's my understanding that if the thing 12 overloads, it stops and it's a big wait. Am I correct on 13 that? I see some of you nodding. 14 Two things. One, see if you can't work it out 15 to where six people get on and the rest of you wait for the 16 next trip, rather than having it break down and the ten people 17 wait in the elevator. And, also, could you please allow the 18 Court Reporter to be in the first crowd up, because she has 19 some things she has to do on the fourth floor during each 20 break. Okay? Thank you-all. 21 (RECESS) 22 JUDGE POTTER: It's a small point, but it goes 23 back to Mr. Smith's paralegals, but I don't know what they're 24 keeping track of, but several plaintiffs have mentioned to my 25 sheriff that apparently Doctor Thompson -- at least they feel, 9 1 9 2 and I haven't even bothered to observe him to see if it's true 3 or not -- is using facial expressions or nodding his head when 4 he agrees with Hans Weber and making faces when he doesn't 5 agree with him or whatever. So can you just ask Doctor 6 Thompson till he gets to the witness stand to kind of keep -- 7 and it's hard for people that aren't lawyers to not get 8 involved with what's going on. 9 MR. SMITH: It's hard for the lawyers. I've got 10 called down for indicating an answer to a witness by doing my 11 head like that. 12 JUDGE POTTER: It's particularly tough to 13 influence the witness when he's on videotape. I'm sure it's 14 unconscious, you nod; you hear things you don't like, you 15 shake your head. 16 MR. STOPHER: It may also be that he was talking 17 to Mr. Freeman about something. I don't even know that it 18 related to that. 19 JUDGE POTTER: As I say, I didn't even bother to 20 try and check it out. 21 (To Sheriff Cecil) You want to bring them around? 22 SHERIFF CECIL: The jury is now entering. All 23 jurors are present. 24 JUDGE POTTER: Okay. Please be seated. Mr. 25 Smith, do you want to continue with the deposition of Doctor 10 1 Weber? 2 MR. SMITH: Did we get the last exhibit handed 3 out? Okay. 4 (VIDEO DEPOSITION OF DOCTOR WEBER CONTINUES) 5 MR. SMITH: That's it, Your Honor. We, again, 6 misstated the time left. 7 JUDGE POTTER: At least it's on the short side. 8 Mr. Smith, do you want to call your next witness? 9 MR. SMITH: Yes, Your Honor. At this time we'd 10 call Doctor Leigh Thompson. 11 JUDGE POTTER: Sir, would you raise your right 12 hand, please. 13 14 DOCTOR W. LEIGH THOMPSON, after first being duly 15 sworn, was examined and testified as follows: 16 17 JUDGE POTTER: Would you have a seat in the 18 witness box. Please keep your voice up and state your first 19 and last names loudly, please. I tell you what, just wait a 20 second till they get the equipment back where it's out of the 21 way. 22 Ms. Jones, you indicated you had a question? 23 JUROR JONES: Yes. 24 JUDGE POTTER: Yes, ma'am. Would you step up 25 here, please. 11 1 (BENCH DISCUSSION) 2 JUDGE POTTER: Okay. Ms. Jones, it's important 3 that you speak into the microphone because that's what's 4 picking up what's going on here. You can speak up. 5 JUROR JONES: My concern is the depositions that 6 we hear, is what the witnesses say when they are questioned 7 more important than what the documents say? 8 JUDGE POTTER: Okay. Why don't you go ahead and 9 retake your seat. 10 (BENCH DISCUSSION CONCLUDED) 11 JUDGE POTTER: Ladies and gentlemen, Ms. Jones 12 asked me a question, and I don't give information to one juror 13 that I don't give to everybody so I'll just answer it. She 14 asked me about documents versus what witnesses say. And all I 15 can tell you is at the end of this case it will be your-all's 16 job to decide what the facts are, and you will just have to 17 take a witness's testimony and a document, and if they're the 18 same or different, make up your mind about what the facts are. 19 There's no magic rule that a piece of paper is more important 20 than what a person says or what a person says takes precedence 21 over what a piece of paper says. 22 Is that the question you kind of asked me, Ms. 23 Jones? 24 JUROR JONES: (Nods head affirmatively). 25 JUDGE POTTER: Okay. Thank you-all. 12 1 Would you state your name loudly and clearly for 2 the jury, please. 3 DOCTOR THOMPSON: My name is Wilmer, W-I-L-M-E-R; 4 Leigh, L-E-I-G-H; Thompson, T-H-O-M-P-S-O-N, Jr. 5 JUDGE POTTER: And if you'll answer Mr. Smith's 6 questions. 7 8 EXAMINATION ___________ 9 10 BY_MR._SMITH: __ ___ _____ 11 Q. How old a man are you, sir? 12 A. Fifty-six years old. 13 Q. Doctor Thompson, you are a medical doctor? 14 A. Yes, sir. 15 Q. You are not a psychiatrist? 16 A. I am not. 17 Q. You are the chief scientific officer for Eli 18 Lilly and Company; is that correct? 19 A. Yes, sir, Mr. Smith. 20 Q. How many scientists are there at Eli Lilly and 21 Company? 22 A. There are about 4,000 people who work in 23 research, although there are other scientists who work in 24 production. Of those 4,000, just under 1,000 have Master's or 25 doctoral-level certification in one or another branches of 13 1 science. 2 Q. So there would probably be approximately 5,000 3 scientists at Eli Lilly and Company? 4 A. I'm sorry. I was including the something under 5 1,000 in with the 4,000 altogether. 6 Q. Four thousand then? 7 A. More or less. 8 Q. And you are the chief of those 4,000 scientists? 9 You're the chief scientific officer; is that correct, sir? 10 A. No, sir. That's not a fair description of my 11 position. Actually, it was in my last job that most of those 12 people reported in one way or another to me. Currently, not 13 very many of the scientists report directly to me in the usual 14 sense of reporting. 15 Q. All right. You, though, have the designation as 16 the chief scientific officer? 17 A. Yes, sir. 18 Q. And your duties now, as I understand it, are to 19 report to the chairman of the board of Eli Lilly and Company, 20 Mr. Tobias; is that right? 21 A. Yes, sir. Mr. Randy Tobias is my boss. 22 Q. And Mr. Randall Tobias is not a medical doctor, 23 is he? 24 A. No, sir. 25 Q. He is not a scientist, either, is he? 14 1 A. No, sir. 2 Q. And you report as the chief scientist to Mr. 3 Tobias and to the board of directors of Eli Lilly and Company, 4 do you not, sir? 5 A. Well, my specific boss is Mr. Tobias. As part 6 of my obligations to Mr. Tobias, I obviously have some 7 reporting obligation to the board and to many other people at 8 Lilly. 9 Q. Prior to that, you were, what, sir? 10 A. My last position at Lilly was as executive 11 vice-president of Lilly Research Laboratories, reporting to 12 Doctor Perelman, who reported to the chairman and CEO. 13 Q. And Doctor Perelman has since retired? 14 A. Yes, sir. 15 Q. You were one of the top scientists involved in 16 the approval of Prozac at the Food and Drug Administration, 17 were you not? 18 A. Yes, sir. 19 Q. And you were one of the top scientists from 20 Lilly involved in the scrutiny that Prozac received by the FDA 21 subsequent to this approval, were you not? 22 A. Yes, sir. 23 Q. You, by virtue of your training as a medical 24 doctor, are trained in critical care and in intensive care 25 medicine; is that correct, sir? 15 1 A. Yes, sir. 2 Q. You are not a psychiatrist? 3 A. I am not a psychiatrist. 4 Q. When you deal with matters of psychiatry, you 5 look to psychiatrists at Lilly to give you assistance in 6 forming opinions, do you not? 7 A. Yes, sir. 8 Q. At this time, who is the psychiatrist at Lilly 9 most knowledgeable concerning Prozac? 10 A. There are actually a number of them, and I 11 would -- I can give you a number of names. I would hesitate 12 to speculate who the most knowledgeable is. 13 Q. Let me ask you this, then, Doctor Thompson. Who 14 has written more and who has been most intimately involved in 15 analyzing the questions presented in connection with whether 16 or not Prozac is associated with suicidality or violent, 17 aggressive behavior? 18 A. Well, I think of at least three people who are 19 psychiatrists: Charles Beasley, David Wheadon and Doctor 20 Heiligenstein; now currently a Lilly employee, previously one 21 of our consultants, Doctor Tollefson, but there are others who 22 are also involved now. 23 Q. Doctor Charles Beasley has written extensively 24 on this subject, has he not? 25 A. Yes, sir. 16 1 Q. And have you asked Doctor Beasley to come here 2 and testify in this case, since he's a psychiatrist and has 3 written extensively on this subject? 4 A. I'm sorry, sir. I haven't asked anyone to come 5 here and testify. 6 Q. Do you know whether or not the Lilly lawyers 7 have asked Doctor Beasley to come here and give the jury the 8 benefit of their opinion in connection with this product? 9 MR. FREEMAN: Your Honor, we object. 10 JUDGE POTTER: Sustained. I'm going to sustain 11 the objection, Mr. Smith. 12 Q. Does Doctor Beasley have opinions that he has 13 discussed with you concerning the safety and efficacy of 14 Prozac? 15 A. Yes, sir. 16 Q. And do you consider his opinions credible and 17 reliable? 18 A. Yes, sir. 19 Q. Have you asked him to come express in person his 20 opinions to this jury? 21 MR. FREEMAN: Judge, that question has been 22 asked and answered. 23 JUDGE POTTER: I'm going to sustain the 24 objection, Mr. Smith. 25 Q. Is Doctor Beasley currently employed by Eli 17 1 Lilly and Company? 2 A. Yes, sir. 3 Q. Is he currently in Indianapolis, Indiana? 4 A. I have no idea where he is today; that's his 5 main headquarters. 6 Q. Where was he when you last saw him? 7 A. He was in Indianapolis when I last saw him. 8 Q. Two hours up Interstate 65? 9 A. If you drive fast. 10 Q. You mentioned Doctor Heiligenstein. 11 A. Yes, sir. 12 Q. Is Doctor Heiligenstein in Indianapolis at this 13 time? 14 A. I don't know where he is today, but that's where 15 his office is. 16 Q. Is he still employed by Eli Lilly and Company? 17 A. Yes, sir. 18 Q. And he is a psychiatrist, as is Doctor Beasley? 19 A. Yes, sir. 20 Q. And Doctor Heiligenstein has written and studied 21 the issue of Prozac and violent, aggressive behavior in 22 detail, has he not, sir? 23 A. Yes, sir. 24 Q. Have you asked him to appear and talk to this 25 jury in connection with this case? 18 1 MR. STOPHER: Your Honor, may we approach the 2 bench for just a moment? 3 (BENCH DISCUSSION) 4 MR. STOPHER: Your Honor, one of Mr. Smith's own 5 motions in limine was to exclude argument and suggestions 6 about the absence of witnesses at this trial, and in violation 7 of his own motion and his own order now, he is persisting to 8 ask about witnesses who are not required to be here under 9 subpoena. He's deposed them. He could have videotaped them 10 and did and any more of this and... 11 MR. SMITH: The Court overruled the motion, by 12 the way. 13 MR. STOPHER: The motion was sustained. 14 MR. SMITH: The motion was overruled. 15 JUDGE POTTER: Regardless of whether the motion 16 is overruled or not, I think you can say they're Lilly 17 employees; it's two and a half hours up the way. But to ask 18 whether Lilly asked them to be here or not, I'm going to 19 sustain the objection, and don't keep asking the question. 20 MR. SMITH: Okay. 21 (BENCH DISCUSSION CONCLUDED) 22 Q. You had given me the name of another 23 psychiatrist at Eli Lilly and Company. 24 A. I think I gave you two: Doctor David Wheadon 25 and Doctor Gary Tollefson. 19 1 Q. Doctor David Wheadon is no longer employed by 2 Lilly, is he? 3 A. That's correct. 4 Q. Doctor Tollefson, is he still employed by Lilly? 5 A. Yes, sir. 6 Q. And is he still in Indianapolis? 7 A. Well, his office is in Indianapolis; I don't 8 know where he is today, either. 9 Q. Have you, as the chief scientific officer of Eli 10 Lilly and Company, Doctor Thompson, spoken with any experts 11 who are scheduled to testify at the trial of this case for Eli 12 Lilly and Company? 13 A. I'm not sure that I know the people that are 14 scheduled to testify and, therefore, I want to be careful in 15 answering that. I have spoken or at least corresponded 16 electronically with Doctor Fuller, who I believe is going to 17 testify. I have corresponded electronically, but not recently 18 verbally with Doctor Tollefson, and if you will give me the 19 list of people scheduled to testify, I'll tell you whether 20 I've talked to them or not. 21 Q. I'll give you a few off the top of my head. 22 Doctor Griest from Madison, Wisconsin? 23 A. I haven't talked to or corresponded with him in 24 several years. 25 Q. Do you know Doctor Griest? 20 1 A. Yes, sir. 2 Q. Do you respect his judgment as a psychiatrist? 3 A. Yes, sir; I do. 4 Q. Doctor Schwab. Do you know a Doctor Schwab? 5 A. I don't think so. 6 Q. How about a Doctor Granacher? 7 A. I've heard of Doctor Ranacher's name and I may 8 have met him, but I certainly can't be specific about that. I 9 can't place him. 10 Q. Have you corresponded with or talked with him 11 concerning this case, as chief scientific officer of Eli 12 Lilly? 13 A. Certainly not since I've had this job, but I 14 don't think I corresponded with him earlier, either. I can't 15 remember. Do you mean Winniker or Ranacher? W-I-N? 16 Q. Granacher from Lexington, Kentucky. 17 A. No. I don't think I know who that is. 18 Q. You joined Eli Lilly and Company in 1984, did 19 you not? 20 A. No, sir. I joined April 1, 1982. 21 Q. At that time the application for Prozac was in 22 the IND phase with the United States Food and Drug 23 Administration, was it not? 24 A. There was work going on to begin putting 25 together the New Drug Application, but since the New Drug 21 1 Application hadn't been approved, by definition it was under 2 the exemption of the NDA rules, which we, as slang, call the 3 IND phase; yes, sir. 4 Q. So am I correct when I say it was in the IND 5 phase, Doctor Thompson? 6 A. Depending on how you want to use that slang 7 term, we were, in fact, when I arrived, beginning to put 8 together the New Drug Application document. 9 Q. And the New Drug Application was complete and 10 filed with the United States Food and Drug Administration in 11 September 1983; is that right? 12 A. Yes, sir. That's correct. 13 Q. That document is a document called NDA, isn't 14 it? 15 A. Yes, sir. 16 Q. And that means New Drug Application, doesn't it? 17 A. Yes, sir. It's the application asking for 18 permission to put the drug in interstate commerce in the 19 United States of America. 20 Q. And the Food and Drug Administration, by virtue 21 of its rules and regulations, states that in order to submit 22 an NDA, the sponsor of the drug must submit information that 23 the sponsor, the manufacturer of the drug, feels supports the 24 safety and efficacy of the product? 25 A. That's partly true, Mr. Smith. But the FDA is 22 1 very precise about all of the information that has to be 2 contained. 3 Q. I understand that. 4 MR. STOPHER: Can he finish his answer, Your 5 Honor? 6 JUDGE POTTER: Let him finish his answer, Mr. 7 Smith. 8 A. I interpreted your question as meaning or 9 suggesting that they only require that we submit information 10 that supported the drug, and that's not correct. 11 Q. No. The NDA, in fact, requires that you submit 12 all scientific information known concerning the drug, doesn't 13 it, Doctor Thompson? 14 A. Isn't the word pertinent, all pertinent 15 information? Pertinent? I haven't read that for a few years, 16 but I thought that was the word. 17 Q. As chief scientific officer of a major 18 pharmaceutical company, is that your understanding, that the 19 FDA, when you file the NDA, wants all pertinent information 20 concerning the safety and efficacy of a drug known at that 21 time by the manufacturer of the drug? 22 A. Well, the facts speak for themselves. That's my 23 best memory of the front page of the NDA, but I haven't seen 24 one for a number of years. 25 Q. That NDA, in requiring pertinent knowledge 23 1 concerning the safety and efficacy of the drug, goes further, 2 does it not, and requires that you continue to provide to the 3 Food and Drug Administration information that the manufacturer 4 considers pertinent to the safety and efficacy of the drug; 5 correct? 6 A. Yes, sir. 7 Q. In other words, if something comes up after 8 September 1983 in connection with Prozac that's felt to be 9 pertinent to the safety of the drug, Lilly is supposed to let 10 the FDA know about it, isn't it? 11 A. The FDA is very precise about the mechanism of 12 that reporting, and there are a variety -- as you know, a 13 variety of mechanisms prescribed specifically in the 14 regulations. 15 Q. Regardless of how you do it, it's got to be 16 reported to the FDA? 17 A. Yes, sir. 18 Q. The reason for that, obviously is, Doctor 19 Thompson, that this is a situation where the state of the 20 knowledge concerning the drug, even though the manufacturer 21 may feel that the -- that they have evidence of safety and 22 efficacy to support FDA approval of a drug, they're continuing 23 to do clinical trials, the matter is being continued to be 24 investigated, the FDA knows that, Lilly knows that, so the FDA 25 wants additional information to transpire over a period of 24 1 time, don't they? 2 A. Yes, sir. Even today, after 15 million people 3 have been on the drug, we continue to report the adverse 4 events of this drug exactly the way the FDA asks. 5 Q. Right. Because the FDA is continuing -- Lilly 6 and the FDA, I assume both, continue to be interested in the 7 safety of this drug. 8 A. Absolutely. 9 Q. And right now, one of the requirements that the 10 FDA requires is that you advise them of adverse events in 11 connection with Prozac, isn't it? 12 A. Absolutely. 13 Q. And one way that Lilly advises concerning 14 adverse events in connection with the Prozac is by filing a 15 specific form with the government; correct? 16 A. Yes, sir. 17 Q. That's called an FDA Form 1639, isn't it? 18 A. It's an FD-1639, but Lilly has an exemption from 19 the specific form and we've added to the form to make it more 20 voluminous, but it's in essence equivalent to a 1639 plus an 21 extra page of information. 22 Q. The information that's contained on that 1639 is 23 information concerning the postmarketing experience with 24 Prozac, isn't it? 25 A. That's correct under the FDA regulations, but 25 1 Lilly has elected for many years to use the same form to 2 report at clinical trial or premarketing adverse events, as 3 well. That's not an FDA requirement; it's our election to do 4 that for completeness. 5 Q. Because Lilly feels that postmarketing and 6 premarketing experience with a drug is relevant to the safety 7 of the drug; correct? 8 A. Exactly. 9 Q. As I understand it, the Food and Drug 10 Administration collects adverse-event data and computerizes 11 that data? 12 A. Yes, sir. In the United States, my 13 understanding is about 90 percent of adverse events get to the 14 regulator from companies like Lilly or sponsors; whereas, in 15 other countries like the UK, a vast majority of the adverse 16 events come from individual practitioners or patients. 17 Q. All right. So the data that is submitted by the 18 manufacturer is data that is recorded on computers by the FDA? 19 A. I think the FDA maintains a computer data base, 20 but I wouldn't want to certify to its completeness. 21 Q. It's called the SRS data base, isn't it? 22 A. If you say so. 23 Q. Spontaneous Reporting System? Those are not 24 terms that are unfamiliar to you, are they, Doctor Thompson? 25 A. I actually learned about them from you during 26 1 the deposition. 2 Q. So you're familiar with those terms as you sit 3 here now? 4 A. Yes, sir. 5 Q. And you were certainly familiar with the 6 requirements of FDA reporting adverse events, weren't you? 7 A. Yes, sir. 8 Q. Long before I ever took your deposition, weren't 9 you? 10 A. That's correct, sir. 11 Q. Additionally, you know that for a number of 12 years, and you knew before I took your deposition, that the 13 FDA collected and monitored this adverse-event data, didn't 14 you? 15 A. Yes, sir. But in terms of a computer data base, 16 I think that's relatively recent. 17 Q. It's now on a computer data base; you know that 18 now? 19 A. I think so. Yes, sir. 20 Q. And it's called the SRS system, isn't it? 21 A. Yes, sir. 22 Q. Additionally, since we're talking about this, 23 Eli Lilly and Company maintains their own computer data base 24 concerning adverse events in connection with their products, 25 don't they? 27 1 A. Absolutely. 2 Q. And specifically in connection with Prozac, 3 don't they? 4 A. No. That's not correct, sir. It began in 1983, 5 and it was the first in the industry, and 40 other major 6 companies have come to look at how we do it so they can copy 7 it. And it had nothing to do with Prozac at the time we 8 implemented it; we just thought that was the right thing to 9 do. 10 Q. No. Listen to my question, Doctor Thompson. 11 Specifically you keep information in your date base concerning 12 adverse events specifically in connection with Prozac, as well 13 as other products? 14 A. Well, I'm having trouble with the word 15 "specifically." All Lilly products marketed anywhere in the 16 world or tested anywhere in the world, even if it has nothing 17 to do with the Food and Drug Administration, we keep the 18 safety data in the Drug Experience Network. Prozac is one of 19 those and so it's there, too. 20 Q. That's all I'm asking. You keep information on 21 Prozac in your data base, don't you? 22 A. Yes, sir. 23 Q. And that's called a DEN data base? 24 A. Drug Experience Network. 25 Q. Okay. Well, let's back up a little bit because 28 1 we're talking about, at least with respect to SRS data, data 2 that is postmarketing data. And I believe you said earlier 3 that postmarketing data is considered as relevant scientific 4 information concerning the safety and efficacy of a drug; 5 correct? 6 A. Yes, sir. 7 Q. Now, let's go through a few things in connection 8 with what we've heard already in this lawsuit about clinical 9 trials and things of that nature. Okay? 10 A. Yes, sir. 11 Q. When you went to Lilly in 1982, there had been 12 some clinical trials that had already been begun and completed 13 in connection with Prozac? 14 A. Yes, sir. 15 Q. There were trials that were under way in 16 connection with Prozac? 17 A. Yes, sir. 18 Q. And since you started, there have been other 19 trials that have begun and completed in connection with 20 Prozac? 21 A. Several hundred. 22 Q. Now, when we talk about clinical trials, we're 23 talking specifically about testing of a pharmaceutical product 24 on -- if we're talking about human clinical trials, humans; 25 correct? 29 1 A. Yes, sir. 2 Q. And the Food and Drug Administration in 3 connection with Prozac, fluoxetine hydrochloride, did not do 4 any independent human clinical trials, did they? 5 A. I think that's correct. 6 Q. The Food and Drug Administration, in fact, did 7 not do any independent animal trials in connection with 8 Prozac, did they? 9 A. I think that's correct. But they do maintain a 10 toxicology facility, as you know. 11 Q. But do you know of any toxicology studies that 12 the FDA did in connection with Prozac? 13 A. No, sir. I said I think they have done nothing 14 in the way of animal studies with it. 15 Q. When you say toxicological studies, are you 16 talking about just animal studies? 17 A. Yes, sir. I'm sorry. I should have made that 18 clear. Animal studies. 19 Q. All right. So that in the drug approval 20 process, the testing process that's done in connection with a 21 drug under investigation, the drug's given to animals; is that 22 right? 23 A. Yes, sir. 24 Q. Now, it's a fact, isn't it, that in connection 25 with Prozac, Prozac was given to animals, was it not? 30 1 A. Yes, sir. 2 Q. And that Prozac was given to Lilly animals, 3 wasn't it? 4 A. Well, I think all the toxicology studies 5 certainly in the NDA were done in Lilly laboratories, so I 6 guess they were Lilly animals. We don't breed them. 7 Q. They were at Lilly Indianapolis, weren't they? 8 A. Or Greenfield; yes, sir. 9 Q. You have a specific laboratory where you 10 maintain animals to give experimental drugs, don't you? 11 A. Yes, sir. 12 Q. And those tests were done in Indianapolis by 13 Lilly employees, weren't they? 14 A. Either Indianapolis or just outside of 15 Indianapolis, in Greenfield, where the major toxicology labs 16 are. 17 Q. There weren't any animal studies or toxicology 18 studies done by the Food and Drug Administration by FDA 19 employees in Washington, were there? 20 A. Not that I'm aware of. 21 Q. After you did your animal studies, you also did 22 studies in normal, healthy humans; is that right? 23 A. I certainly didn't, but Doctor Lemberger began 24 those on May the 11th of 1976. 25 Q. Doctor Lemberger was a Lilly employee, wasn't 31 1 he? 2 A. Yes, sir. 3 Q. And he officed at that time in Indianapolis, 4 Indiana? 5 A. Yes, sir. 6 Q. And the laboratory or the clinic where he worked 7 was housed in Indianapolis, Indiana, wasn't it? 8 A. At the medical school at Wishard Hospital. 9 Q. And that was in Indianapolis, wasn't it? 10 A. Yes, sir. 11 Q. And the humans that volunteered for those 12 studies were individuals residing in Indianapolis? 13 A. Well, during -- 14 Q. Or surrounding area? 15 A. During the course of the study, yes, but I 16 couldn't tell you exactly where they were recruited. 17 Q. The point is, is that the normal-healthy-human 18 studies were done by Eli Lilly and Company, weren't they, 19 Doctor Thompson? 20 A. Certainly the initial ones. 21 Q. And the normal-human studies were not done in 22 Washington by FDA employees, were they? 23 A. No, sir. 24 Q. Those animal studies and those healthy-human 25 studies, were they done according to what we've heard termed 32 1 here as protocols? 2 A. Yes, sir. 3 Q. Were those protocols drafted and designed by 4 Lilly employees or were they drafted and designed by the Food 5 and Drug Administration? 6 A. Well, I'm sure that they were drafted primarily 7 by Lilly employees. I'm not sure how much input the FDA had 8 into them because I wasn't there at the time that these 9 specific studies were begun. 10 Q. All right. Generally speaking, though, in doing 11 toxicology studies and normal-healthy-human studies, in 12 connection with the protocols for those studies, Lilly 13 employees draw up those protocols? 14 A. Yes, sir. But as a general rule we also go and 15 talk with the FDA about any specific aspects of them. 16 Q. I'm going to get to that in a minute. But as 17 far as the actual drafting of the protocols -- 18 A. Done by Lilly employees. 19 Q. -- that's done by Lilly employees, isn't it? 20 A. Yes, sir. 21 Q. Now, protocols are simply the rules and 22 regulations and guidelines for the test that's going to be 23 employed, aren't they? 24 A. Yes, sir. 25 Q. Kind of a blueprint or written instructions 33 1 concerning how the test is going to be conducted? 2 A. Yes, sir. 3 Q. And this was -- the blueprints, rules and 4 instructions were designed by Lilly? 5 A. Yes, sir. 6 Q. After you did the normal human studies, you were 7 able to begin studies on Prozac in depressed individuals, were 8 you not? 9 A. Yes, sir. "You" now meaning Lilly, not me 10 specifically? 11 Q. Yes. I understand you didn't come till 1982 and 12 that the clinical trials in depressed individuals began prior 13 to your arriving at Lilly; is that right? 14 A. Yes, sir. 15 Q. When I say "you," I'm going to give "you" a 16 Lilly slang or text, and sometime I'll use it in the 17 impersonal "you." I might say "y'all," too, so watch out for 18 that. 19 The normal -- the depression studies were 20 studies or clinical trials where Lilly gave the drug to 21 depressed individuals, were they not? 22 A. Well, let me be specific. I think Lilly had 23 investigators who were academicians known in the field who 24 followed Lilly-designed protocols to give the drug to the 25 patients and collect the data as specified in those protocols. 34 1 I don't think we studied any depressed patients ourselves as 2 Lilly scientists, I don't think. 3 Q. All right. Well, let's back up, then. Lilly 4 did design the protocols for these depression studies, didn't 5 they? 6 A. Yes, sir. 7 Q. And in designing those protocols, you kind of 8 create the parameters of the study, don't you? 9 A. Yes, sir. 10 Q. You'll select the type of people generally to be 11 involved in the study; for instance, this is a depression 12 study so you've got to get some depressed people, don't you? 13 A. Yes, sir. 14 Q. And that's a decision made by Lilly; right? 15 A. Yes, sir. Again, since I wasn't there, I can't 16 tell you the amount of input from the individual 17 investigators. I know that since I've been at Lilly the usual 18 procedure is to talk with prospective investigators, not 19 necessarily all of them but at least some of the key ones, to 20 get their input to the design. 21 Q. Well, Doctor Slater and Doctor Stark, the 22 initial depression-study medical monitors have testified that 23 they talked with people within Lilly concerning the design of 24 the protocols. Did you hear that testimony? 25 A. Yes, sir; I did. There was one other medical 35 1 monitor I think you mentioned, not now but earlier, that I 2 don't really know his name. 3 Q. I didn't know him, either. The only people 4 we've deposed were the only medical monitors involved in those 5 depression trials before you came, that I'm aware of, are 6 Doctor Stark and Doctor Slater, whose depositions have been 7 read or played in this case, and it was their testimony -- it 8 might have been in or out -- but it was their testimony that 9 they talked with other people within Lilly and didn't go out 10 and talk to investigators in connection with the actual 11 designing of the protocol. 12 MR. FREEMAN: That's not an accurate quote of 13 the testimony, Your Honor. If he's going to refer to 14 something specifically, I think he should do so. 15 JUDGE POTTER: Mr. Smith, if you've got -- why 16 don't you just ask the question without paraphrasing what 17 other witnesses have said on that point. 18 Q. Well, do you dispute that Doctor Stark and 19 Doctor Slater didn't consult with investigators in designing 20 the initial depression trial? 21 MR. FREEMAN: That's not an appropriate 22 question, Your Honor. 23 JUDGE POTTER: Why don't you just ask him 24 whether he knows, Mr. Smith, rather than trying to paraphrase. 25 Q. Do you know? 36 1 A. All of my knowledge was from the depositions 2 we've heard here. I was talking specifically earlier about 3 the policies after I came to Lilly, and these studies have 4 been made before I came. So of my own knowledge I can't tell 5 you anything other than what we've already heard. 6 Q. All right. So the point simply is, is that the 7 protocol is designed in house at Lilly, I mean, it's something 8 that Lilly conceives of and makes decisions on; correct? 9 A. Yes, sir. We would not do a study that we 10 disagreed with the protocol. But, again, currently at least, 11 we often -- often, not always -- consult with outside people, 12 including people at the FDA. 13 Q. All right. But the early depression trials, you 14 don't know of any outside consultants that were called in? 15 A. No, sir; I do not. 16 Q. Once that protocol is designed, investigators 17 are hired; correct? 18 A. Yes, sir. 19 Q. And those investigators are individuals that are 20 hired to conduct the trial, are they not? 21 A. Yes, sir. 22 Q. And those individuals, those investigators are 23 hired by Eli Lilly and Company, aren't they, Doctor Thompson? 24 A. Yes, sir. 25 Q. They are paid by Eli Lilly and Company to 37 1 conduct the trial according to Lilly's protocol, are they not? 2 A. Yes, sir. 3 Q. And those investigators are required to conduct 4 that trial according to guidelines set out by Lilly's 5 protocol, aren't they? 6 A. Yes, sir. 7 Q. Then Lilly's investigators report back the raw 8 data to Eli Lilly and Company, don't they? 9 A. Yes, sir. 10 Q. The investigators don't report that raw data 11 directly back to the Food and Drug Administration, do they, 12 Doctor Thompson? 13 A. Usually not. 14 Q. And you don't know of any instance in connection 15 with Prozac where an investigator sent in his or her data 16 directly to the FDA, do you? 17 A. It would be very unusual to send data, but they 18 do have the capability and there have been some instances, 19 although I don't think with Prozac, where they reported 20 specifically directly to the agency. But as a general rule, 21 no, they send it to Lilly. 22 Q. And Lilly in Indianapolis then reports that data 23 to the Food and Drug Administration; correct? 24 A. Yes, sir. 25 Q. Now, as I understand it, when Lilly reports that 38 1 data to the Food and Drug Administration, they do it in a 2 couple of broad ways: Number One, they send microfiche copies 3 of the actual case report forms to Washington, D.C., do they 4 not? 5 A. You're not required to use microfiche, but the 6 FDA so often asks you to, that that's one of the actual ways 7 we send it. Lilly's pioneered electronic submissions done by 8 computer -- electronic records. 9 Q. But in connection with the Prozac clinical 10 trials, that raw data, which is the case report forms filled 11 out by the investigators, any paper filled out by the 12 investigator is sent by Lilly to Washington in microfiche 13 form? 14 A. For the Prozac NDA I think you're exactly 15 correct. I think all of the investigator's documents, all of 16 them went in the form of microfiche to the FDA. 17 Q. The reason for that is, obviously, you're 18 talking about an enormous amount of paper, aren't you? 19 A. Yes, sir. I think we've submitted 2.5 million 20 pages of regulatory submissions around the world as of today. 21 Q. Okay. And Washington doesn't want all that 22 paper? 23 A. No. Well, let's say that they want all the data 24 but -- 25 Q. I didn't say data, I said paper. Washington 39 1 doesn't want all that paper, that's why you submit it to them 2 in microfiche form? 3 A. Yes, sir. I said that they ask for fiche of 4 certain parts of the submission. 5 Q. And what they do is if they look at that raw 6 data -- can we call that raw data? 7 A. Yes, sir. 8 Q. And if they need to look at that raw data, they 9 can pull that out by putting a film in there and wheeling 10 through it and getting that data? 11 A. I think it was sent as fiche, which are 12 individual sheets, rather than as microfilm reels, but I think 13 that's true. 14 Q. Whatever, it's made where it's more exact? 15 A. Yes, sir. 16 Q. That's the way the raw data is submitted, in 17 very exact form as opposed to the actual paper? 18 A. Well, of course they audit all the actual papers 19 both at the investigator's office and at Lilly's archives, but 20 it's not all of it because we submit a lot of chemistry and a 21 lot of toxicology raw data, and I think that goes in on paper. 22 Q. I'm talking about the investigator's files. 23 A. In the clinicians -- my knowledge in the Prozac 24 NDA, at that stage we were still submitting that data in 25 microfiche. 40 1 Q. All right. Additionally, because that raw data 2 is -- there's some limits with the way you can work with it, 3 isn't there, Doctor Thompson? 4 A. What do you mean? It's all there. 5 Q. It's all there, but there's limits in the 6 ability to retrieve that data and perceive that data, isn't 7 there? 8 A. I disagree with that, Mr. Smith. It's all 9 indexed highly, and I would frankly say to you that if I were 10 a reviewer at FDA I would rather have it on microfiche with a 11 reader than have boxes and boxes of paper sitting in the hall 12 outside my office. The reason they want it is it's easier to 13 work with. 14 Q. I understand that, but did you say 2.5 million 15 or billion? 16 A. I'm sorry. I said million pages is what my 17 understanding is of Lilly pages of submissions worldwide on 18 Prozac as of now. 19 Q. On Prozac only. What I'm saying is you've got 20 2.5 million pages of documents that are submitted. It doesn't 21 make any difference what form you submit that in; as long as 22 you're not submitting it in computer form, it's going to be 23 difficult for somebody to get any kind of meaningful 24 information out of that 2.5 million pages of documents, isn't 25 it, Doctor? 41 1 A. I disagree with that, too, Mr. Smith. After 2 all, Lilly relies on the same documents for our analysis in 3 the understanding of the data, as well. It's obvious if 4 you've got 2 million pages, you've got a big document. But 5 we've spent a lot of time indexing it and so forth correctly. 6 And the FDA works very hard in going through every single 7 datum. It's difficult, and I don't know a way of doing it 8 easier, other than the electronic submissions that we're now 9 pioneers of doing. 10 Q. That's what I was getting to before you got 11 defensive on me. 12 MR. STOPHER: Objection to that comment and move 13 that that be stricken from the record. 14 JUDGE POTTER: Mr. Smith... 15 Q. I'm not making any point other than you gave the 16 Food and Drug Administration in addition to that raw data, 17 electronic summary data, didn't you? 18 A. We need to be careful on what time we're talking 19 about with Prozac. In the NDA, to my knowledge I don't think 20 there were electronic records sent with that. We've gradually 21 migrated to providing more and more electronic data. 22 Q. But don't you provide summaries of data? Didn't 23 you provide summaries of data to the FDA in connection with 24 Prozac? 25 A. Yes. We provide every single original data and 42 1 summary, and summary of the summaries, and summaries of the 2 summaries of the summaries. 3 Q. That's simply where I was going with you, Doctor 4 Thompson. You know, you've got a big bunch, 2.5 million pages 5 of data and you've got summary after summary after summary 6 after summary, don't you? 7 A. Yes, sir. 8 Q. Now, that summary after summary after summary is 9 done at Eli Lilly and Company in Indianapolis, isn't it? 10 A. Yes, sir. 11 Q. And that's submitted to the Food and Drug 12 Administration in addition to the raw data, isn't it? 13 A. Yes, sir. 14 Q. So I think where we were was we were at the 15 depression clinical trial phase where you have a clinical 16 trial involving, let's say, 40 people and you're going to have 17 a placebo-controlled clinical trial, so you'll give 20 people 18 Prozac and you're going to give 20 people placebo; right? 19 A. You want to be precise? Because you're close, 20 you're very close. 21 Q. All right. Tell me how closely I missed the 22 answer, Doctor Thompson. 23 A. Well, you didn't miss it. It's just to be 24 really precise, in a controlled trial like that with random 25 allocation of the patients, every new patient would have, the 43 1 way you described it, 50-50 odds of getting placebo, say, or 2 Prozac. Now, it doesn't always work out that at the end of 40 3 patients you've got exactly 20 and 20; it could be 21 and 19. 4 And I'm not trying to play games, I just want to make sure 5 that we're precise. 6 Q. All right. The goal is to try to have as close 7 to an equal and randomized number of individuals on Prozac and 8 on comparitor drugs or placebo? 9 A. Yes, sir. Although, you can have unbalanced 10 designs. I mean, you can design it so you want to have twice 11 as many people on Prozac as placebo or you may test many 12 different doses. So it doesn't necessarily -- when you say a 13 placebo-controlled trial, it doesn't necessarily mean that 50 14 percent of the people are going to be on placebo. 15 Q. Okay. But if you want to get a fairly accurate 16 representation of head-up competition between Prozac and 17 placebo, you generally try to put an equal amount of people on 18 Prozac as placebo, don't you? 19 A. Again, I don't want to play games, but let's be 20 very precise. The FDA says that our fixed-dose studies of 21 Prozac are the best that were ever done and set new standards 22 for the industry. And in those studies, you know, we had 23 one-fourth got placebo, one-fourth got a low dose, and 24 one-fourth that got a medium dose, and one-fourth that got a 25 high dose. So in that case, about a fourth would be on 44 1 placebo and three-fourths would be on one or another dose of 2 Prozac. So I think that's more elegant, and that's what the 3 FDA told us. 4 Q. It seems like, Doctor Thompson, in responding to 5 my questions, you kind of have a tendency to talk about how 6 Lilly is the leader in these matters and things of that 7 nature. 8 MR. STOPHER: May we approach the bench, Your 9 Honor? 10 JUDGE POTTER: Mr. Smith. 11 (BENCH DISCUSSION) 12 MR. STOPHER: Your Honor, I object to Mr. Smith 13 making these stage comments to Ms. Zettler, which he intends 14 for the jury to hear, which he just made on his way up here. 15 I object to him continually making statements to Doctor 16 Thompson about the way in which he's answering the questions. 17 It is inappropriate for him to be commenting and making his 18 judgments on the way in which this witness is testifying; the 19 jury is only entitled to make that. 20 MR. SMITH: This is an adverse, extremely 21 hostile witness. 22 JUDGE POTTER: The only thing I heard where Mr. 23 Smith made a comment in questioning was when he said 24 defensive, and I sustained an objection. And I'm going to 25 sustain an objection to Mr. Stopher if you make any comments 45 1 to Ms. Zettler, you know. And, Mr. Smith, the only thing I 2 have to do is -- after the second or third time, is call you 3 down in front of the jury. So just ask her to hand you the 4 paper and don't make comments to her about what's going on. 5 MR. SMITH: Well, we characterize this piece of 6 paper as -- in a specific way and all I was doing is asking 7 whether it was that piece of paper. 8 MR. STOPHER: No. You said to her on the way up 9 here, "Mr. Stopher doesn't even let me get my question out." 10 You can say that up here, but you can't say it to her. 11 JUDGE POTTER: I'm sustaining the objection to 12 comments about the other attorneys or the demeanor of the 13 witness made to Ms. Zettler. 14 MR. SMITH: Could I have the courtesy of being 15 able to complete my question before Counsel jumps up and 16 objects and calls me to the bench? I'm not trying to ask 17 objectionable questions and I'd like to at least -- I mean, 18 the Court doesn't even have my question completed. 19 JUDGE POTTER: Well, I think an attorney is 20 allowed to object before somebody asks a question, because a 21 lot of times asking a question the damage is done. And if he 22 makes an objection -- and the same rule will apply for you. 23 You make your objection, and if it's something he can't state 24 right off the bat then we'll come up here and talk about it. 25 And, oftentimes, I have to ask, "What is your question going 46 1 to be, Mr. Smith." So I sustain the objection. 2 MR. SMITH: Okay. I have this document. I 3 might as well give you that. 4 JUDGE POTTER: Okay. 5 (BENCH DISCUSSION CONCLUDED) 6 MR. SMITH: Doctor Thompson, let me hand you an 7 exhibit. 8 Your Honor, is it proper for me to approach the 9 Witness to hand him an exhibit? 10 JUDGE POTTER: Yes, sir. You can approach the 11 Witness. 12 Q. Plaintiffs' Exhibit 118, and ask if you can 13 identify that document. 14 A. Thank you, sir. (Reviews document) Yes, sir. 15 This is a five-page memo -- it's actually two pages -- from 16 Mitch Daniels to me with a carbon copy to Mr. West, and then 17 attached to it is a graph, and attached to that is a two-page 18 memo from some people called Lengel and Leavell to Mr. West. 19 Q. The subject of this communication from Mr. West 20 is upcoming TV appearances; is that correct? 21 A. Yes, sir. 22 Q. The letter is dated, or the note is dated April 23 15th, 1991, and is addressed to you from Mr. E. A. West; is 24 that right? 25 A. I think this is from Mr. Daniels to me, carbon 47 1 copy to Mr. West. 2 Q. Okay. You've seen this document before? 3 A. I've seen the first two or three pages. I'm not 4 100-percent sure I've seen the last two. 5 MR. SMITH: We move for admission of Plaintiffs' 6 Exhibit 118. 7 MR. FREEMAN: Your Honor, we have a relevancy 8 objection. 9 JUDGE POTTER: Approach the bench. 10 (BENCH DISCUSSION) 11 MR. FREEMAN: The statute -- the document is not 12 relevant to any issue in this case. It talks about practices 13 for television audiences; it doesn't have a thing to do with 14 the case at bar. It is dated well after the event here, April 15 15, 1991. It is a communication between Doctor Thompson and 16 the public relations director or media directions person at 17 Lilly. 18 JUDGE POTTER: Okay. Mr. Smith, what is the 19 relevance of it? 20 MR. SMITH: The relevance is to his entire 21 testimony. He's giving the company line. He's practiced 22 giving this. He's coached giving this. I'm entitled to let 23 the jury know that these questions are something that's been 24 fielded to him before and it affects the answers that he 25 gives. 48 1 JUDGE POTTER: I'm going to sustain the 2 objection. 3 MR. SMITH: Can I question him concerning the 4 document? 5 JUDGE POTTER: You can ask him if he appeared on 6 TV, if he is their spokesperson and all of that kind of stuff, 7 but I'm sustaining the objection to the document. 8 (BENCH DISCUSSION CONCLUDED) 9 Q. The subject of this document is upcoming TV 10 appearances, is it not? 11 MR. FREEMAN: Your Honor, the subject is 12 inappropriate after the objection has been specifically 13 sustained. 14 JUDGE POTTER: Mr. Smith, you can ask him his 15 role and what he's done for Lilly, but I'm sustaining the 16 objection to the document and discussing the document. 17 Q. In connection with your work at Lilly, Doctor 18 Thompson, you've given many interviews and made many TV 19 appearances, have you not? 20 A. Some, at least. Yes, sir. 21 Q. You've been characterized as a media pro by your 22 public relations director and your lobbying people, have you 23 not? 24 A. I worked for NBC-TV for a while back earlier 25 before I went to Lilly. 49 1 Q. As late as April 15th, 1991, in connection with 2 Prozac, you've been described as a media pro, haven't you, 3 Doctor Thompson? 4 A. They say so. 5 Q. And you have been coached on how to give 6 interviews and respond to questions concerning Prozac, haven't 7 you? 8 A. They've tried. 9 Q. They have given you specific message goals to 10 consider when you give interviews or when you speak concerning 11 Prozac and the issue of violent, aggressive behavior and 12 suicidality, haven't they? 13 A. I don't want you to go too far with that, Mr. 14 Smith. Yes. They've provided me with their thoughts about 15 goals. I am my own person and I speak for myself. 16 Q. I didn't imply that you didn't, but you have 17 received input from specialists in communication concerning 18 how to communicate in connection with this question, haven't 19 you? 20 A. Yes, sir. 21 Q. And you have been given the specific points to 22 emphasize in connection with this issue before this jury, 23 haven't you? 24 A. I've been given their impression of what this -- 25 whoa. Before this jury? I don't think that's correct. This 50 1 was, in fact, in 1991, and it had to do with TV appearances. 2 And it is a correct statement to say that other people said 3 that they thought that these were the right points. Again I 4 want to emphasize, I speak for myself. 5 Q. Do you mind telling this jury that no medicine 6 for a brain disease has ever been more thoroughly researched 7 than Prozac? 8 A. That is correct. I will assert that. Yes. 9 Q. Do you mind telling the jury that it's the 10 disease, not the drug, that causes any problems that might be 11 related to Prozac at all? 12 A. No. I wouldn't make that statement without 13 qualifying it, sir. 14 Q. All right. You've also been coached in how to 15 give your tone, the impression to give in connection with 16 speaking about Prozac in this issue, haven't you, Doctor 17 Thompson? 18 A. Yes, sir. 19 Q. They've asked you to show compassion? 20 A. Yes, sir. 21 Q. To place yourself on the patient's side? 22 A. Yes, sir. Are you going to get to Number Three? 23 Q. You've been asked to just quote medical 24 authorities in connection with the tone of how you respond to 25 these questions? 51 1 A. Yes, sir. 2 Q. And they've told you to be friendly? 3 A. Actually, they said it comes naturally. I 4 thought that was a great compliment. 5 Q. Then they've talked about how to handle specific 6 questions about Prozac, haven't they? 7 A. Yes, sir. 8 Q. And they wanted to help you in connection with 9 answering these questions? 10 A. That was their intent. 11 Q. All right. I don't know where we were. I was 12 just trying to get some information about the relationship of 13 the amount of documents that were sent to the FDA by Lilly in 14 connection with Prozac versus the amount of summaries that 15 were sent to the FDA by Prozac. Would it be accurate to state 16 that the raw data was sent that would have comprised 2.5 17 million documents to the FDA? 18 A. No, sir. I think -- I hope I was specific. The 19 2.5 million pages relates to submissions to all regulators 20 worldwide since the beginning of Prozac to today, not the FDA 21 number, which is a smaller number, and obviously not every 22 page is raw data. 23 Q. All right. How many pages have been submitted 24 to the FDA then? 25 A. I don't know specifically, but it's around half 52 1 or perhaps even a little more than half of the 2.5 million. 2 Q. How many summaries have been submitted to the 3 FDA by Lilly? 4 A. Well, I don't know because almost every time you 5 send in a large volume of data they ask you to send in some 6 sort of a summary or index, so there must be hundreds of 7 summaries, hundreds. 8 Q. Why do you suppose, Doctor Thompson, that the 9 Food and Drug Administration asks a manufacturer to summarize 10 documents and data that has been submitted by Lilly? 11 A. I think it helps them choose which of the raw 12 data they're going to look at, because sometimes they look at 13 it all and sometimes they just pick out individual cases or 14 individual animal studies that they want to look at. 15 Q. Did you know or have you heard or has anybody 16 made you aware as the chief scientific officer of Eli Lilly 17 and Company that the Food and Drug Administration only looked 18 at less than 50 case-report forms in connection with the 19 Prozac depression trials? 20 A. I don't remember that. I remember Doctor Dobbs 21 saying that they probably didn't look at all of it, but the 22 auditing records order exists because, again, they audit at 23 the investigator's site and they audit at Lilly the data that 24 we send them and they choose how much to audit. So they can 25 audit 100 percent, if they want to. Ordinarily, they randomly 53 1 select certain works and if they don't see any problem -- the 2 original one done by Doctor Kapit and Doctor Leber and Doctor 3 Temple, and I know that they went through a lot of the 4 original case-report forms from talking to them, but I 5 certainly don't know what percentage they looked at. 6 Q. I'm not talking about 50 percent; I'm talking 7 about that the FDA only looked at 50 patients who were in the 8 depression trials to actually look at the actual case-report 9 forms filled out on the patients. Would you be surprised to 10 hear that? Have you heard that, number one? 11 A. I've never heard that; no, sir. 12 Q. Does that surprise you that the Food and Drug 13 Administration only looked and examined 50 patients who were 14 in the Prozac clinical trial? 15 A. It doesn't surprise me because for the next NDA 16 they asked us not to send the clinical-report forms, only to 17 send the electronic records of them. 18 Q. So it doesn't surprise you that they only looked 19 at 50 out of the 4,000 patients? 20 A. No, sir. I think the original NDA had about 21 2,060 some-odd patients total, including the normal 22 volunteers, in all the studies. 23 Q. So it doesn't surprise you that the FDA would 24 only look at the case-report forms on 50 individual patients? 25 A. If they audited 50 and saw no problems, it's not 54 1 unreasonable for them to stop auditing. 2 Q. After the clinical trials were done and the data 3 was submitted to the Food and Drug Administration, that data 4 is reviewed in some way, form or fashion by the Food and Drug 5 Administration, is it not? 6 A. Yes, sir. 7 Q. Additionally, that same data collected in the 8 clinical trials will be reviewed and analyzed by other 9 regulatory bodies if Lilly elects to submit application in 10 other countries for marketing that product? 11 A. That's not precisely correct, sir. Most other 12 countries -- this drug's on the market in 75 countries, but 13 let's speak in general. Most other countries, like the major 14 European countries, request summaries, expert opinions and 15 only a small amount of the data. To my knowledge, there is no 16 other country that wants all the raw data like the Food and 17 Drug Administration does. 18 Q. Well, the testimony up to this point, Doctor 19 Thompson, has been in connection with Prozac and the 20 application to market Prozac. 21 MR. FREEMAN: Your Honor, here we go again with 22 another paraphrase of testimony. We object to that. It's a 23 mischaracterization of the prior testimony. 24 (BENCH DISCUSSION) 25 JUDGE POTTER: Okay. Mr. Smith, what was your 55 1 question going to be? 2 MR. SMITH: That all the data that was submitted 3 to Germany -- all data that was submitted to Germany was all 4 the data that Lilly had at the time. 5 MR. FREEMAN: You said the testimony has been. 6 MR. SMITH: By Doctor Weber. 7 JUDGE POTTER: Just ask him the question. 8 MR. SMITH: Is it -- Can I not ask a witness a 9 question about what other sworn testimony is in this case? 10 JUDGE POTTER: I'm sorry. I asked you what your 11 question was and you told me what your question was and it 12 didn't include that lead-in. Now, give me your question 13 again, beginning to end. 14 MR. SMITH: The testimony has been in this case 15 that all the data that was submitted to the German BGA was the 16 same data that was submitted to the FDA in September 1983 NDA. 17 JUDGE POTTER: Now, I think that's -- and now 18 the question. That's the lead-in; what's the question going 19 to be? Do you agree with that, disagree with that or what? 20 MR. SMITH: Yeah. 21 JUDGE POTTER: I think that's a little different 22 than what you said before. Do you have any objection that's 23 what the guy said? 24 MR. STOPHER: We just object to characterizing 25 and paraphrasing. He can ask the question, "Was the same data 56 1 submitted?" 2 JUDGE POTTER: Objection is overruled. 3 (BENCH DISCUSSION CONCLUDED) 4 Q. In September 1983, Lilly submitted data to the 5 Food and Drug Administration that supported safety and 6 efficacy, in Lilly's opinion? 7 A. Yes, sir. 8 Q. That same data was submitted to the BGA in 9 support of its application to manufacture Prozac -- or to 10 distribute Prozac in Germany, was it not? 11 A. Yes, sir. But I want to be very clear about 12 what I can testify to and what I can't. 13 MR. SMITH: We would object to this part of the 14 answer after "yes, sir" as being nonresponsive to the 15 question, Your Honor. 16 JUDGE POTTER: He answered it yes or no, then 17 he's entitled to explain his answer. 18 A. There are several explanations. I can't testify 19 to exactly what went to the BGA because I have no individual 20 knowledge of that. Secondly, I can tell you that it's my 21 understanding that all of the data on all of the patients, for 22 example, were submitted in one form or another; however, it is 23 my understanding that Germany and virtually no other European 24 regulator wants the individual case-report forms that you 25 mentioned. So it's my belief, but it's only a belief, that in 57 1 fact the case-report forms probably did not go to the BGA but 2 that all of the data that were on the case-report forms 3 probably did go there. So it's a matter of a definition of 4 data, and I think your original question is raw data, and 5 that's why I wanted to be very precise about it. 6 MR. SMITH: We renew our objection about the 7 nonresponsiveness of his answer. 8 JUDGE POTTER: Objection is overruled. 9 Q. Do you agree or disagree, Doctor Thompson, that 10 the BGA -- that the application was made to the BGA at a time 11 when Lilly felt like their data supported safety and efficacy 12 of the drug? 13 A. I agree with that. 14 Q. And do you agree that the BGA's review of 15 whatever data was submitted to them by Lilly was done with the 16 review of the safety and efficacy of Prozac in mind? 17 A. Yes, sir. 18 Q. Lilly -- do you know when Lilly conducted the 19 first clinical trial in Germany? 20 A. No, sir, but I believe it was after September 21 1983. 22 Q. Was it after September 1984, when Doctor Schenk 23 wrote her draft of her reply to the BGA? 24 A. I'm sorry, sir. I wasn't responsible for it and 25 I don't have individual knowledge of the timing or even the 58 1 number of the German studies. 2 Q. Didn't international medicine come under your 3 medical supervision in 1984? 4 A. No, sir, not then. And even later when parts of 5 international reported to me, each individual country stood 6 alone and the medical scientists in that country reported to 7 the director of that affiliate and they didn't report to me at 8 all. The only international people that ever reported to me 9 were the group of scientists at Earlwood Manor outside of 10 London. 11 Q. How did you know that the BGA didn't want 12 individual case-report forms? 13 A. Because for ten years I've been in international 14 meetings negotiating regulatory procedures around the world 15 and I know the leaders of the BGA and they tell me what they 16 want. I've never had the responsibility of making those 17 submissions, and I can't even tell you the exact content of 18 what our German affiliate sends to the BGA. I'll tell you to 19 the best of my ability. 20 Q. You just don't know what was sent to the BGA? 21 A. I've testified to the best of my ability what 22 was sent to the BGA is the initial submission. 23 Q. The September 1983 initial submission that was 24 submitted to the FDA? 25 A. I think they got all the data that was submitted 59 1 to the FDA in one form or another. 2 Q. So can we say that the BGA and the FDA were 3 looking at the same data? 4 A. Well, you made such a big point about looking at 5 the original case-report form pages, that's why I wanted to be 6 precise. I don't think the BGA got the original case-report 7 form pages. I don't think they ever get them. 8 Q. Well, do you think that -- did you see any 9 instances where the BGA had indicated back in '84, '85, '86, 10 '87 or '88, that they intended to reject the Prozac 11 application because they didn't have all the individual 12 case-report forms? 13 A. I don't think that was the issue and I don't 14 think it's ever been the issue with the BGA. 15 Q. Then why did you bring it up? 16 A. Because, sir, you made such a point about the 17 original case-report forms and that being the raw data, and I 18 didn't want to testify incorrectly that they had all the raw 19 data because I don't think they did. 20 Q. But that wasn't a problem as far as the BGA was 21 concerned, at least as from what you're aware? 22 A. I think they largely look at summaries and 23 original opinions and they don't look at original data to 24 anything like the original FDA. 25 Q. Well, wait a second. They had more than just 60 1 summaries and expert opinions? 2 A. Yes, sir. They had tabulations of the data. 3 Q. And that was sent to them by Eli Lilly and 4 Company, wasn't it? 5 A. It was sent to them by our German affiliate, 6 which is part of Eli Lilly and Company. 7 Q. Which was sent to the German affiliate from Eli 8 Lilly in Indianapolis? 9 A. Yes, sir. We sent that to the German affiliate, 10 for sure. 11 Q. Let's change gears a little bit, Doctor Thompson 12 and start talking about something that we agree on. The 13 presumption of the mode of action of Prozac is that it 14 physiologically inhibits the reuptake of serotonin; is that 15 right? 16 A. Yes, sir. 17 Q. It is presumed, is it not, that depression can 18 be a result of either an imbalance or an abnormality in 19 serotonin in individuals? 20 A. I think that the majority of depressed people 21 have a lack of serotonin influences in the brain; yes, sir. 22 Q. You as a scientist subscribe to the theory that 23 depression is related to serotonin levels in the brain? 24 A. Yes, sir. 25 Q. I understand that you may not be a 61 1 neurobiologist like Doctor Fuller or a psychiatrist like 2 Doctor Beasley, for instance, but as far as a medical doctor, 3 you're aware of the theory that depression is a result of an 4 imbalance of some sort in the level of serotonin in the brain? 5 A. Well, I don't think that's precisely correct. I 6 don't think it's an imbalance, which suggests it could be 7 either high or low. I think that in people with depression, 8 they have less serotonin influences in the brain than normal. 9 But I'm not sure that's true of all, because our treatment of 10 depression only works in about two-thirds of patients, so 11 there may be a third of patients that have some other 12 mechanism that I don't know about. 13 Q. I was going to ask you if you had any knowledge 14 of any data that would confirm or deny what Doctor Weber 15 testified to in his videotape deposition, that in 70 percent 16 of individuals, antidepressant treatment was effective? 17 A. Yes, sir. My number would be two-thirds, and it 18 obviously changes from study to study. In some studies, drugs 19 that we think are active don't work any better than sugar 20 pills, but I think around two-thirds of people with depression 21 will respond to any of the treatments that I know of that are 22 thought to work. 23 Q. Now, you're not -- based on all the clinical 24 trial data and all the studies done on Prozac up to the time 25 that it was approved by the FDA, you're not saying that Prozac 62 1 is more efficacious than existing antidepressants? 2 A. No, sir. We never thought it would be any 3 better than tricyclics in terms of the percentage of people 4 that would be helped. We just thought that by being specific 5 it would lack some of the side effects. 6 Q. It was the side-effect profile of Prozac that 7 would make it most beneficial as a treatment modality for 8 depressed individuals; is that correct? 9 A. Yes, sir. 10 Q. And your clinical trials never established 11 Prozac as being more efficacious than other existing 12 antidepressants, did they? 13 A. No, sir. 14 Q. That means -- we may have been using the term 15 efficacious here. That means it doesn't work any better, 16 doesn't it? 17 A. Well, you know, if you get into the whole thing, 18 the fact that fewer drop out and fewer people have bad side 19 effects, some people would say that makes Prozac more 20 efficacious. I think what you meant, and I agree with you, is 21 if you measure depression and you measure how many people have 22 significant improvement with depression, I think it's 23 two-thirds with Prozac, and two-thirds with tricyclics and 24 two-thirds with MAIO inhibitors and two-thirds with every drug 25 I know. 63 1 Q. But you're not saying that Prozac works any 2 better than imipramine, for instance? 3 A. In the treatment of depression, I think you're 4 absolutely right. 5 Q. And a reason that a medical doctor might choose 6 Prozac over other existing antidepressants is that it has a 7 different side effect -- 8 A. Well, I think there are three reasons. One is 9 more people can take it longer because the side effects are 10 not as troublesome, and the other thing is if you take a huge 11 overdose of Prozac it's very likely you'll survive, whereas, 12 if you take a week or two's worth of tricyclics, you may well 13 die of the overdose. 14 Q. I thought you were going to give me three 15 reasons. 16 A. I stuck the side effects in with Number One. 17 Sixty-some percent of people taking tricyclics will have a dry 18 mouth, and the most frequent side effect with Prozac is 19 probably nausea, which is 17 to 23 percent, something like 20 that, so that they're less troubled. Fewer people quit taking 21 their medicine because of troublesome side effects. 22 Q. What's the second most frequent side effect with 23 Prozac? 24 A. It depends on which studies, which dose. 25 Q. You said nausea was most frequent. In whatever 64 1 study that came from, what is the second most frequent side 2 effect with Prozac? 3 A. There are five adverse events that are more 4 frequent with Prozac at twenty milligrams for four weeks than 5 placebo, and those are: Nausea is the most frequent -- I 6 can't quote you the figures on the others, but it's nausea, 7 loss of appetite, diarrhea, vomiting and asthenia. Asthenia, 8 feeling weak, punk, bad. Those are the five that are 9 significantly more frequent on Prozac at 20 milligrams for 10 four weeks than on placebo. But if you look at -- that's 11 depression. I said depression. But if you look at other 12 diseases or other doses or other durations, you'll get a 13 different array of side effects. 14 Q. When do you get this nervousness, anxiety, 15 agitation, activation side effect? 16 A. Primarily at higher doses. If you look at the 17 study that was done -- I think Doctor Beasley published it at 18 the side-effect profile at 0, 20, 40, 60 and 5 milligrams, 19 what you'll notice is that in dose studies at 20 milligrams 20 the side-effect profile that you mentioned are pretty much the 21 same as placebo, but you certainly see more of that 22 nervousness, sleep disorder -- I've forgotten all the things 23 you mentioned -- you certainly see more of that at 40 and 60 24 milligrams, even 80. 25 Q. Well, maybe I'm confused. In our Exhibit 50, 65 1 which is Doctor Slater's Exhibit 1, the paper entitled 2 Inhibition of REM Sleep by Fluoxetine, do you recall that 3 paper? 4 A. I think you had it here in the trial. 5 MR. SMITH: May I give a copy to the Doctor? 6 JUDGE POTTER: Certainly. 7 Q. If you'll look on Page 385, in the second full 8 paragraph it says, "After the cats have been receiving," do 9 you see that? 10 A. Yes, sir. 11 Q. It says, "After the cats have been receiving 12 drug treatment for a few days, it was noticed that their 13 pupils were dilated but still responsive to light. The degree 14 of mydriasis -- 15 A. That's dilated pupils. 16 Q. -- seemed to be dose related." And it goes on 17 to say -- Doctor Slater goes on to say, "By the fourth day of 18 drug treatment, the cats receiving the larger doses, which had 19 been friendly for years, began to growl and hiss. They became 20 distinctly unfriendly, but with careful handling it was 21 possible to administer the drug in the usual way. The cats 22 seemed to see clearly and did not seem to be hallucinating. 23 They became less irritable toward the end of the second week 24 of drug administration. After cessation of the drug 25 treatment, the cats returned to their usual friendly behavior 66 1 in a week or two, those on the higher doses recovering more 2 slowly." Do you see where I was reading that? 3 A. Yes, sir. 4 Q. Was Doctor Slater still with Lilly when you 5 joined Lilly? No. He retired in '79, didn't he? 6 A. He wasn't there when I -- I've never met him. 7 Q. Have you had an opportunity to discuss this 8 paper with Doctor Slater? 9 A. No, sir. I've never met him and I haven't 10 talked to him. 11 Q. Have you read this paper? 12 A. Not until you just handed it to me. I knew you 13 presented it earlier in the trial, but this is a 1977 study in 14 cats, and I was answering your question on the basis of 15 science and 15 million patients that have taken the drug and 16 10 thousand patients on clinical trials. 17 Q. Can you get the relationship from behavior from 18 looking at cats and mice and stuff like that? You certainly 19 can't ask a cat if he's feeling depressed today, can you? 20 A. I was surprised by the statement that the cats 21 weren't hallucinating because I don't know how to ask a cat 22 that one, either. You give drugs to animals because you like 23 to predict what's going to happen in people. And what you -- 24 Q. And do you -- 25 MR. STOPHER: Let him finish his answer. 67 1 MR. SMITH: I'm sorry. I thought he was 2 finished. 3 A. And generally what you do is you give huge doses 4 to animals because that may alert you to some side effect you 5 may see in the first patients you treat. I must tell you from 6 my own experiments, if you give various drugs to animals like 7 cats in very high doses, you'll get all kinds of misbehavior 8 in the animals, including the fact that you can kill them. 9 Q. Well, these cats didn't die. 10 A. If you give high enough doses of Prozac or any 11 other drug to animals, you can kill them. 12 Q. They didn't here. 13 A. It's very hard to kill animals with Prozac. 14 It's one of the neat features of the drug. 15 Q. This is Lilly cats, I guess. This was done by 16 Doctor Slater at the Lilly Research Laboratories, wasn't it? 17 A. Yes, sir. Lilly cats. 18 Q. It says they were on larger -- the ones on the 19 larger doses became unfriendly, doesn't it? 20 A. Yes, sir. 21 Q. Which indicates that it was higher than the 22 normal dose; right? 23 A. See, I don't know what normal is for a cat even 24 today, and I know that they didn't know what normal was for a 25 cat then. 68 1 Q. That's an interesting question. What is normal 2 serotonin level, Doctor? 3 A. Where? 4 Q. In cats. 5 A. In cats? 6 Q. Uh-huh. 7 A. Measured where? 8 Q. In cats' brains. 9 A. The whole brain. 10 Q. In the synaptic cleft. 11 A. The synaptic cleft? 12 Q. Yeah. What's the normal serotonin level? 13 A. I don't know. But in the deposition of Doctor 14 Fuller that you were reading, I thought he said he was doing 15 some microdialysis experiments to look at that very piece of 16 data, but I don't know what the results are. 17 Q. What's the normal serotonin level in humans? 18 A. Well, in the blood somebody has the number -- I 19 don't have it on the top of my head, but in the brain in the 20 synaptic cleft I don't even know how you'd study that in human 21 beings. 22 Q. Are you telling me that you can't measure how 23 much serotonin I have in my synaptic cleft? 24 A. I could kill you and measure it, but you 25 probably wouldn't like that. 69 1 Q. If a psychiatrist goes to a depressed individual 2 and asks them what their -- or tries to do some test on the 3 serotonin level in their synaptic cleft, they can't determine 4 that, can they? 5 A. No, sir. I think you know that there have been 6 lots of papers looking at serotonin metabolites and spinal 7 fluid, which is, at best, a very crude index of how much 8 serotonin is in the synaptic cleft. 9 Q. So when the psychiatrist prescribes Prozac to 10 lower the level -- to increase the level of serotonin in the 11 synaptic cleft, that psychiatrist doesn't even know what the 12 level was to start with, does he? 13 A. That's correct. 14 Q. Much less know whether he's really depressed 15 because of a low level of serotonin; correct? 16 A. That requires more than a yes or no. 17 Q. All right. 18 A. The general theory since about the 1950s has 19 been that depression is related to either too little serotonin 20 or too little norepinephrine. There have been hundreds of 21 studies that support the idea that depression is due to too 22 little of one of those two. Frankly, until Prozac we didn't 23 have a drug that would specifically work on only one of the 24 two, so no one knew. And for a long time at Lilly I thought 25 Prozac wouldn't be as good as the tricyclics because it would 70 1 only work on serotonin. 2 Now, Lilly has a second drug that only works on 3 norepinephrine. It has the same effect as Prozac on serotonin 4 uptake, but it only works on norepiniphrine. That drug 5 doesn't work on depression. And the fact that Prozac only 6 works on serotonin and is as good as, as we've talked about 7 before, the ones that work on everything, that, to me, means 8 that pretty much the best we can say about depression today is 9 that, again, most people with depression have a lack of 10 serotonin effect. But I want to be real sure that we remember 11 that there are a third of the people that we call depressed 12 that don't respond to any treatment that I know about, and I'm 13 not sure what's wrong with their brains. 14 Q. All right. Well, can you make any specific 15 statement that any specific individual is specifically 16 depressed because their -- specifically because their 17 serotonin levels are low. 18 A. No, sir. That's an excellent point. And I must 19 tell you that we have massaged the data on Prozac every way I 20 can imagine, looking at age, obesity, sex, everything else you 21 could find, to see if we could predict which patients would 22 respond to it and which wouldn't. And to my knowledge as of 23 today, we don't have anything to distinguish the patients that 24 will respond versus the ones that won't. Except right now 25 we're developing some data that if you measure 71 1 rapid-eye-movement sleep, that effect which is commonly seen 2 in some depressed people, looks like it identifies a 3 population that is more responsive; but that's not proven to a 4 point that all scientists would all agree with it. 5 Q. Would this cat study be anything of significance 6 in that? 7 A. It's tough, because the problem with depression 8 is there's not a lab test you can do, and you are absolutely 9 correct in asserting that. You can't send a blood sample to 10 the laboratory and say, "Is this person depressed?" Virtually 11 the only thing I know you can do in the way of a laboratory 12 test is measure your rapid-eye-movement sleep, which is very 13 expensive. You have to have the patient in a laboratory, you 14 have to put electrodes on their eyes and so forth. It is true 15 that many people with depression have a shortened period of 16 time from the time they fall asleep until rapid-eye-movement 17 sleep begins. And one of the characteristics of drugs that 18 work in depression, as in an animal and patients, it tends to 19 decrease the amount of rapid-eye-movement sleep. So if you 20 said what would be the best laboratory test you could do in 21 animals, certainly in '77, to predict that you had an 22 antidepressant, probably the effect that they saw here in cats 23 of decreasing REM sleep probably is the best thing they had. 24 Q. And would it be a valid predictor of side 25 effects that these cats growled and hissed and became 72 1 unfriendly? 2 A. I would pay a lot of attention to that when I 3 was starting to dose human beings. Absolutely. 4 Q. All right. The fact is, as I understand it, if 5 you could have 16 depressed individuals, you know, like 6 there's 16 jurors here, and you could take their -- if you 7 could -- there's no way you could measure what their serotonin 8 level is to start with? 9 A. Certainly not in the brain, and there's only one 10 rare disease that makes serotonin go up in the bloodstream, so 11 you'd only do that in blood for detecting this one rare kind 12 of tumor. 13 Q. And it's at the brain that's it's important, 14 isn't it? 15 A. Yes, sir. 16 Q. It's the amount available at the synaptic cleft 17 that's important? 18 A. Exactly. 19 Q. And that's exactly what you can't measure? 20 A. You're right. 21 Q. And so if my serotonin level is a certain level, 22 your serotonin is a certain level, the court reporter's 23 serotonin level is a certain level and we got -- each got 20 24 milligrams of Prozac, what is your understanding of how much 25 it would increase each one of our serotonin levels? 73 1 A. I don't know. 2 Q. Is there any way to know? 3 A. Well, again, you can do that in animals, and I 4 think that's what Doctor Fuller said he was working on in his 5 laboratory today, and I don't know the results of those 6 studies. In human beings, I don't think there's a technique 7 that would allow you to measure that in the synaptic cleft 8 today in human beings. 9 Q. So in actual practice, when you're giving Prozac 10 to a variety of individuals, you are exposing that Prozac to 11 individuals with varieties of levels of serotonin availability 12 at the synaptic cleft; is that right? 13 A. Yes, sir. 14 Q. And you don't know how much that Prozac is going 15 to increase the level of serotonin in any individual's 16 synaptic cleft, do you? 17 A. No, sir. 18 Q. Much less, being able to know how much it's 19 going to increase a group of individuals -- serotonin in a 20 group of individuals' synaptic clefts? 21 A. I think what you're asking is, I could not 22 distinguish a group of individuals who would be likely to have 23 more of an effect of Prozac or less of an effect of Prozac. 24 And, as I told you, even if I could distinguish that, I 25 couldn't tell you which ones would have a cure of their 74 1 depression and which ones wouldn't. 2 Q. So if I can understand it, if we have 16 3 individuals, we could very well have 16 different levels of 4 serotonin available at the synaptic cleft; is that right? 5 A. Probably. 6 Q. But you wouldn't be able to know in a living 7 human what that amount is in any of the 16 individuals; is 8 that right? 9 A. That's correct. 10 Q. And so when you administer that Prozac to 16 11 different individuals, you're going to get increase in 16 -- 12 the availability of serotonin in 16 different synaptic clefts; 13 is that right? 14 A. Well, in 16 individuals you'll have probably 15 different effects from Prozac in terms of availability of 16 serotonin in the synaptic cleft; yes, sir. 17 Q. It would be -- at 16 different levels, 18 potentially, couldn't it? 19 A. Probably. 20 Q. And you, in fact, don't know how much an 21 increase in that level of serotonin you're getting at the 22 synaptic cleft, do you? 23 A. I'm sorry. I got lost on that one. You don't 24 know how much increase in serotonin you're getting; that's 25 correct. 75 1 Q. Right. When you administer Prozac, you don't 2 know whether it's getting a twofold increase of serotonin 3 available at the synaptic cleft or a tenfold increase of 4 serotonin available at the synaptic cleft or a hundredfold 5 increase of serotonin available at the synaptic cleft? 6 A. I probably wouldn't guess on numbers quite that 7 high, but I agree with you, I don't know. 8 Q. It just can't be measured? 9 A. It cannot be measured in living humans with the 10 techniques we have today, to my knowledge. 11 Q. So when you administer Prozac, you're 12 administering Prozac when you don't have any test-specific 13 guidelines that you can quantify about serotonin at the 14 synaptic cleft; is that right? 15 A. Other than REM sleep -- which I explained in 16 humans was really experimental; we're just doing the studies 17 now -- I'm not aware that there's a laboratory test which 18 would help guide your therapy of the patient with depression 19 to Prozac or selecting any of the other drugs. 20 Q. You as an internist could draw my blood and get 21 a thyroid level, couldn't you? 22 A. Yes, sir. 23 Q. And you could prescribe some medication -- or 24 you could determine by taking that blood level of whatever, 25 whether or not I had too much -- what is the enzyme that 76 1 thyroid produces? 2 A. Well, the hormone itself is usually just called 3 thyroid hormone, but it exists in several forms and we don't 4 want to go into that. 5 Q. All right. But you could get specific levels, 6 can't you? 7 A. Yes, sir. 8 Q. And there are normal levels of thyroid hormone, 9 are there not? 10 A. It's a little worse than that, and you have to 11 measure the level of thyroid-stimulating hormone as well as 12 the level of thyroid hormone to know whether you're going to 13 treat a patient or not. But you're on the right theme; there 14 is a blood test, which in most patients would tell you that 15 the patient has too much thyroid, too little or just right. 16 Q. But you can't do that with Prozac, can you? 17 A. Well, you can find out whether you've got too 18 much Prozac or not, but you can't do it with serotonin. 19 Q. And so you can't get a serotonin level? The 20 doctor who's prescribing Prozac can't administer any blood 21 test to know whether to give it, Number One, or how much to 22 give, Number Two, can it? 23 A. You cannot do a blood test to make that 24 determination. 25 MR. SMITH: All right. I'm sort of at a change 77 1 in pace, Your Honor. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 77 1 JUDGE POTTER: Okay. Well, maybe this will be a 2 good time to break for lunch. 3 Ladies and gentlemen, I'm going to remind you 4 again, do not permit anybody to speak to or communicate with 5 you on any topic connected with this trial, and any attempt to 6 do so should be reported to me. Do not discuss the case among 7 yourselves or form or express opinions about it. We'll stand 8 in recess till 2:00. 9 (JURORS EXCUSED FOR LUNCH RECESS) 10 JUDGE POTTER: Mr. Stopher, I don't know if I 11 mentioned this, but when a witness is on the stand or part of 12 the case comes along, will one or the other be the objecter? 13 MR. STOPHER: Fine. 14 JUDGE POTTER: I don't care who it is; one of 15 you do it. Thank you-all. 16 (LUNCH RECESS) 17 SHERIFF CECIL: The jury is now entering. All 18 jurors are present. Court is back in session. 19 JUDGE POTTER: Mr. Thompson, I'll remind you 20 you're still under oath. 21 Mr. Smith. 22 Q. Doctor Thompson, as I understand it, you're 23 leaving on a business trip next week; is that right? 24 A. Yes, sir. 25 Q. And are you going to be gone for several weeks; 78 1 is that right? 2 A. I was told that was okay. 3 Q. Yes. I just wanted to make sure we'll have you 4 if we need you for the rest of this week; is that right? 5 A. Oh, yes, sir. 6 Q. Beg your pardon? 7 A. Yes, sir. 8 Q. Doctor Thompson, I'm going to hand you a 9 document that's been marked as Plaintiffs' Exhibit 86 and ask 10 if you can identify that document. 11 A. Yes, sir. This is my electronic memo message of 12 February 7, 1990. 13 MR. SMITH: We would offer Plaintiffs' 86, Your 14 Honor. 15 MR. FREEMAN: No objection, Your Honor. 16 JUDGE POTTER: Be admitted. 17 SHERIFF CECIL: (Hands document to jurors). 18 Q. Let's see if we can go through Plaintiffs' 19 Exhibit 86 and get some sort of identification concerning the 20 circumstances around your writing this memo. As I understand 21 it, Eli Lilly in Indianapolis has an E-mail interoffice 22 communications capacity; is that correct? 23 A. Yes, sir. 24 Q. And what we see as Plaintiffs' Exhibit 86 is a 25 transmission in house at Lilly; is that right? 79 1 A. Yes, sir. 2 Q. This transmission is to several individuals and 3 for -- from you; is that right? 4 A. Yes, sir. 5 Q. And for everybody's benefit, it's to Allan J. 6 Weinstein. He is a medical doctor, is he not? 7 A. Yes, sir. 8 Q. And in February 1990, what was his job with 9 Lilly? 10 A. He was the vice-president of Lilly Research 11 Laboratories, specifically responsible for liaison with all of 12 our international affiliates. 13 Q. At that time would Doctor Weinstein have been a 14 vice-president that reported to you, sir? 15 A. I don't think so on this specific date, but it 16 was around that time that he did begin to report to me. 17 Q. You at that time and he at that time felt it 18 appropriate that you give him instructions in connection with 19 the business of Eli Lilly, at least to some extent? 20 A. To some extent, just like he gave me 21 instructions. 22 Q. But on the corporate totem pole would you have 23 been at a little higher level than he at that time? 24 A. I was slightly higher but, again, I don't know 25 whether he was reporting to me on that day. But somewhere 80 1 around there he began to report to me. 2 Q. Okay. Patrick P. Keohane? 3 A. Keohane. 4 Q. Keohane. Who is -- is Patrick P. Keohane a 5 medical doctor? 6 A. Yes, sir. 7 Q. And what was his job with Lilly at that time? 8 A. At that time he was the medical director of our 9 affiliate in the United Kingdom. 10 Q. And Max Talbott is a Ph.D. doctor who was at 11 that time director of regulatory affairs for Lilly? 12 A. Yes, sir. 13 Q. And Doctor Talbott had been instrumental in 14 interfacing with the FDA in connection with Prozac? 15 A. Yes, sir. 16 Q. Robert L. Zerbe was a medical doctor -- is a 17 medical doctor still, and what was his job at Lilly at that 18 time? 19 A. I think he was an executive director rather than 20 a vice-president at that time, and I think he reported to me 21 and was responsible for much of the U. S. medical group. 22 Q. At one time I believe he was head of Lilly's CNS 23 and endocrinology division; is that right? 24 A. Yes, sir. 25 Q. And you would have been a vice-president in 81 1 charge of a larger group of medical on the corporate level; is 2 that right? 3 A. Yes, sir; at this time. 4 Q. The subject of the correspondence or the E-mail 5 is Prozac safety reports; is it not? 6 A. Yes, sir. 7 Q. It says, "I wish to reemphasize the messages 8 from Bob Zerbe and Max Talbott in this regard in terms of the 9 resource needs to stay absolutely on top of every Prozac event 10 report." Correct? 11 A. Yes, sir. 12 Q. In February 1990, there was some controversy 13 concerning Prozac and its relationship to suicide and violent, 14 aggressive behavior; correct? 15 A. Yes. That's correct. 16 Q. At that time or in that exact month there was 17 published an article by Doctor Martin Teischer, was there not? 18 A. Yes, sir. 19 Q. And where was that article published? 20 A. I don't remember. Can you help me? 21 Q. I believe it was the New England Journal of 22 Medicine or the American Journal of Psychiatry, one of the 23 two, wasn't it? 24 A. I'm sorry. I don't remember. 25 Q. American Journal of Psychiatry. Doctor Teischer 82 1 was a professor of psychiatry and a psychiatrist at Harvard 2 Medical School, was he not? 3 A. He was a faculty member at Harvard and he was 4 based in McLean, but I'm not sure he had a faculty rank of 5 professor; that one, I'm not sure of. 6 Q. Doctor Teischer at that time had written a 7 report raising the question of a possible linkage between 8 Prozac and suicidal thoughts, had he not? 9 A. Yes, sir. 10 Q. And that report had received some publicity by 11 virtue of the nature of his publication? 12 A. Yes, sir. 13 Q. The American Journal of Psychiatry is a 14 prestigious journal, is it not? 15 A. Yes, sir. 16 Q. And Harvard Medical School is a prestigious 17 university, is it not? 18 A. Some of us from Hopkins would question that, but 19 generally I think you're correct. 20 Q. You certainly at the time Doctor Teischer 21 published his report knew of no criticism of Doctor Teischer's 22 competency as a psychiatrist or as a teacher at Harvard 23 Medical School? 24 A. Not at all. 25 Q. In fact, that article that Doctor Teischer 83 1 published in February of 1990 was co-authored by another 2 distinguished psychiatrist and teacher by the name of Jonathan 3 Coale, was it not? 4 A. Who was or is a professor of psychiatry, yes. 5 Q. Doctor Coale, in fact, I believe was senior to 6 Doctor Teischer. Doctor Coale was an older gentleman, or was 7 he? 8 A. I think he's senior in faculty rank; I don't 9 know whether one reports to the other or not. 10 Q. Doctor Coale had, in fact, been an investigator 11 for Eli Lilly and Company, had he not? 12 A. Yes, sir. 13 Q. And had conducted clinical trials in connection 14 with Prozac? 15 A. Yes, sir. I think that's right. 16 Q. And his clinical trial data had been sent to the 17 FDA by Lilly in support of their claims of safety and efficacy 18 of Prozac? 19 A. I'm not 100-percent sure of that. I think he 20 was one of our investigators or consultants. That's the best 21 I can do. 22 Q. And he had investigated and consulted in Prozac? 23 A. I think so. 24 Q. And so that's one of the reasons for your level 25 of concern in February of 1990, was the fact that this article 84 1 had been published and the fact that there was at that time a 2 public question concerning linkage of Prozac and suicidal 3 ideation? 4 A. Well, that was certainly part of the concern. I 5 mean, we would be concerned about any scientific publication 6 addressing any aspect of our product, but it was primarily the 7 lay press coverage that had evoked this particular memo. 8 Q. But the lay press was reporting on an article 9 that had been written by a well-known and well-respected 10 psychiatrist in a well-known and well-respected medical 11 publication; correct? 12 A. Yes, sir. 13 Q. You go on to say, "Anything that happens in the 14 UK can threaten this drug in the U. S. and worldwide." 15 Correct? 16 A. Yes, sir. 17 Q. Was there something in particular in -- I assume 18 by UK you mean England -- United Kingdom? 19 A. That's part of the UK. 20 Q. All right. Was there something in particular in 21 the UK that was going on in connection with Prozac that was 22 causing additional concern? 23 A. If I can explain the background of this, it 24 wasn't anything that I knew specifically in the UK, but we 25 have far more resources in the United States for handling 85 1 safety reports than the affiliates that often will have a 2 relatively small staff, and because this wasn't an issue of 3 any great importance to either the UK affiliate or to the 4 regulators in the UK, what I was concerned about is that they 5 pay a great deal of attention to any safety reports because -- 6 not because it would have any impact in the UK but, in fact, 7 that we needed to be on top of this on a worldwide basis. 8 Q. All right. You say we are now experiencing -- 9 no, I'm sorry. "We are now expending enormous efforts fending 10 off attacks because of (1) relationship to murder and, 11 (2) inducing suicidal ideation." Correct? 12 A. Yes, sir. 13 Q. Now, it says, "The appropriate level of response 14 is indicated by Dan Masica himself and Charles Beasley 15 immediately flying to Boston to talk to authors of paper on 16 suicidal ideation." Correct? 17 A. Yes, sir. 18 Q. Dan Masica is a psychiatrist? 19 A. No, sir; he is an internist. But at that time 20 he was director of the neuropsychiatric medical component at 21 Lilly. 22 Q. He was a Lilly physician? 23 A. He is a Lilly physician; yes, sir. 24 Q. And Charles Beasley was a Lilly employee who is 25 and was a psychiatrist at the time; correct? 86 1 A. Yes, sir. 2 Q. And when you say they were immediately flying to 3 Boston to talk to the authors of the paper, you're talking 4 about Doctor Teischer and Doctor Coale? 5 A. Yes, sir. 6 Q. At Harvard. Says, "We have numerous foes. The 7 FDA is very, very skitterish. I have talked with Paul Leber 8 twice in the last several days." Correct? 9 A. Yes, sir. 10 Q. Who is Paul Leber? 11 A. Doctor Leber is a psychiatrist who is director 12 of the division of the FDA called the Neuropharmacological 13 Drugs Division that was responsible for Prozac. 14 Q. Doctor Leber was extremely instrumental from the 15 FDA's side in reviewing the Prozac application? 16 A. Instrumental, yes; strict, yes. He was very 17 much involved. 18 Q. When I say instrumental, he was involved? 19 A. Absolutely. 20 Q. And continued to be involved in the Prozac- 21 related issues maybe up until now? 22 A. Including today. 23 Q. All right. You say you talked to him twice in 24 the last several days and you date that -- this is dated 25 February 7th, 1990; is that right? 87 1 A. Yes, sir. 2 Q. Now, Doctor Leber is head of the division that 3 approved Prozac? 4 A. Yes, sir. 5 Q. And you were at that time head of the medical 6 division of the company that made Prozac? 7 A. Yes, sir. 8 Q. And you and he were talking on the telephone? 9 A. Yes, sir. 10 Q. And you had talked twice in the last several 11 days? 12 A. Yes, sir. 13 Q. You go on to say, "We must not allow one day to 14 elapse on follow-up, flying to, investigating, et cetera, 15 everything about Prozac. Bob Zerbe can correct me for a wild 16 guess, but I would think we have 20 full-time equivalents, at 17 least, working just on Prozac postmarketing safety and 18 support, and, if necessary, we will stop everything else going 19 on to provide more." Correct? 20 A. Yes, sir. 21 Q. When you say you had 20 people working on Prozac 22 postmarketing safety full time, would those people have been 23 in Indianapolis or would they have been worldwide? 24 A. No. My reference here would be just to the 25 people in Indianapolis working on it. 88 1 Q. And what were they doing, reviewing adverse- 2 event reports concerning suicidal ideation and murder that had 3 been coming into the Lilly facility there in Indianapolis? 4 A. Well, that would be part of their work, sir, but 5 in fact they were involved in looking at all of the adverse- 6 event reports on -- this is just the team working on Prozac. 7 And after you get a publication like that, especially lay 8 press, you get a huge increase in the number of adverse-event 9 reports, and what I wanted to be sure of was that we were 10 right on top of every one and did the appropriate follow-up 11 right away. 12 Q. And you-all were flying people -- I'm sorry. 13 Did I cut you off? 14 A. I just had one other thing, and, that is, 15 because of that report we were going back and looking at all 16 the data that we had in our data base that addressed those 17 issues. 18 Q. Well, you say that -- 19 JUDGE POTTER: Wait just a second, Mr. Smith. 20 (To Sheriff Cecil) Will you see if Ms. Williams is okay? 21 JUROR WILLIAMS: Sorry. Thank you. 22 JUDGE POTTER: Are you okay, Ms. Williams? Do 23 you want to take any kind of break? 24 JUROR WILLIAMS: I'll be all right in a minute. 25 JUDGE POTTER: Well, we'll wait a minute. (To 89 1 Sheriff Cecil) Will you have Mr. Smith when this is over check 2 the cooler again? 3 SHERIFF CECIL: Sure. 4 JUROR WILLIAMS: Okay. 5 JUDGE POTTER: Okay. I'm sorry, Mr. Smith. Go 6 ahead. 7 Q. You say in your memo, though, that you had 20 8 full-time equivalents, at least, working just on Prozac 9 postmarketing safety and support. 10 A. Yes, sir. 11 Q. I get the impression from that that you had 20 12 people at that time reviewing postmarketing reports; is that 13 not correct? 14 A. Well, part of that work would be going back into 15 our own data base and, in fact, the whole scientific 16 literature to get any information we could that was related to 17 this point. 18 Q. But were you going back to your postmarketing 19 data base or your clinical trial data base in February of 20 1990? 21 A. Everything including the medical literature. 22 Q. All right. But it does say that they're working 23 just on Prozac postmarketing safety, doesn't it? 24 A. Yes, sir. 25 Q. And you say, "If necessary, we'll stop 90 1 everything else going on to provide more." 2 A. Yes, sir. 3 Q. More postmarketing surveillance? 4 A. Yes, sir. 5 Q. You say, "Every significant event about Prozac 6 has been a show stopper with twelfth-floor meetings 7 immediately with Earl, Mel, et cetera." Correct? 8 A. Yes, sir. 9 Q. Earl is Doctor Herr; is that right? 10 A. Herr. Doctor Earl Herr. 11 Q. Who was at that time -- 12 A. At that time he was executive vice-president of 13 the corporation and he was responsible for all of our research 14 and production. 15 Q. He was one to whom you reported at that time; is 16 that right? 17 A. Well, through Doctor Perelman at that time. I 18 had originally reported to Doctor Herr directly earlier, but 19 for some years I had reported through the next name, Mel 20 Perelman. 21 Q. Mel is Mel Perelman, and at that time in 22 February 1990, he was president of Lilly Research 23 Laboratories, was he not? 24 A. Yes, sir. 25 Q. The twelfth floor to which you're referring is 91 1 where the executives -- the top executives with the 2 corporation office, was it not? 3 A. Yes, sir. 4 Q. It's where the chairman of the board maintained 5 his office then? 6 A. And now. 7 Q. And now. You didn't office there then, did you? 8 A. No, sir. 9 Q. You office there now, don't you? 10 A. Yes, sir. 11 Q. You say, "There cannot be a fumble of even minor 12 proportions on this one because political pressures and 13 perceptions and public news, not science, could cause us to 14 lose this one, five exclamation marks." Right? 15 A. Yes, sir. 16 Q. When you say "could cause us to lose this one," 17 to what are you referring, Doctor Thompson? 18 A. I am saying that something bad could happen to 19 Prozac in terms of a label change, like a black box or getting 20 a black eye in the minds of the practitioners who use it and 21 so forth. And the reason I said "not science" is because I 22 thought the science was firm, we didn't have a problem, but we 23 were getting a lot of publicity that we didn't want. 24 Q. You were getting a lot of postmarketing reports, 25 too, that you were -- because you were concerned? 92 1 A. Especially after the Teischer articles and the 2 news reports there was an enormous increase, but you always 3 expect that, sir, whenever you get a signal report. 4 Q. After you get a signal report? 5 A. If you -- if you have the first report of some 6 unusual event, it could be either good or bad about a drug, 7 that's very common to then see a lot of other papers 8 describing the same thing and a lot of spontaneous reports 9 from practitioners describing the same thing. 10 Q. As I understand it, 90 percent of these 11 spontaneous reports that are received by the FDA are in fact 12 reports that are made to Lilly that Lilly has transmitted to 13 the FDA; is that right? 14 A. Yes, sir. I think so. 15 Q. And Lilly is receiving those reports primarily 16 from medical doctors, are they not? 17 A. Yes, sir. They come in from a whole variety of 18 sources, including our field sales force, individuals calling 19 us. I mean, they can come in from anyone. 20 Q. But the vast majority of your adverse events 21 come from physicians in practice prescribing Prozac? 22 A. Either calling us directly or talking to any of 23 our employees, including our sales force. 24 Q. That's another point. Your employees, your 25 sales force, regularly call on physicians, do they not? 93 1 A. I hope so. 2 Q. And the purposes of these salespeople -- they 3 used to be called detail people back in the earlier days. Are 4 they still called detail people? 5 A. No, sir. 6 Q. Salespeople? 7 A. Professional representatives. 8 Q. All right. The professional representatives are 9 salesmen from Eli Lilly and Company, are they not? 10 A. Fifty-one percent of ours are either pharmacists 11 or nurses, so they really are professionals. 12 Q. I understand that. But they're there to make 13 the doctor familiar with Lilly products? 14 A. Oh, that's correct, sir. Yes, sir. 15 Q. In the hope that those doctors will prescribe 16 Lilly products; correct? 17 A. Well, you know, some people would say that 18 they're there to sell the product; some people would say that 19 they're there to provide information to make sure it's used 20 right. I'd say both. How about that? 21 Q. Did they do both? 22 A. Yes, sir. 23 Q. I'm not criticizing that. Lilly is in the 24 business of selling pharmaceuticals, and most of the 25 pharmaceuticals that Lilly sells are sold only by virtue of a 94 1 medical doctor writing a prescription for those 2 pharmaceuticals? 3 A. I hope all of them are only sold that way. 4 Q. Because Prozac is not an over-the-counter 5 medication that you would be marketing like Advil or some cold 6 remedy; correct? 7 A. No, sir. 8 Q. And it's appropriate, also, that it only be 9 prescribed by a physician? 10 A. Yes, sir. 11 Q. It is a powerful psychotropic medication, is it 12 not? 13 A. It's very effective, as we've talked about. 14 Q. Now, back to the adverse-event reports. Your 15 detail people go into doctors' offices, and if the doctor 16 reports to a detail person a particular experience with 17 Prozac, that detail person is instructed by the corporation to 18 advise the corporation, are they not? 19 A. Yes, sir. I actually put that system in place, 20 so it's a little broader than that. All 30,000 employees of 21 Lilly, including me, are under an obligation to report by 22 telephone, E-mail or telex or fax, electronically, within 48 23 hours of hearing of any adverse experience with any Lilly 24 product anywhere in the world. 25 Q. I understand that, and I believe you've given us 95 1 testimony that if you were on an elevator and you heard 2 somebody that had a bad reaction with Prozac, you would 3 yourself feel an obligation to fill out some type of 4 appropriate report notifying the company so the company could 5 take the appropriate regulatory action; correct? 6 A. As I did last week. 7 Q. All right. The fact is, though, Doctor 8 Thompson, that the majority of these adverse-event reports are 9 event reports that come from professional medical doctors, are 10 they not? 11 A. Yes, sir. 12 Q. And the majority of those, in fact, are obtained 13 by virtue of your own employees being in the doctor's office 14 giving information about Lilly products and getting the 15 doctor's experience with Lilly products, aren't they? 16 A. I think it's more than 50 percent, but it 17 certainly is a very substantial proportion. 18 Q. So when you talk about this wave of adverse 19 events that are reported, things that should be borne in mind 20 is several things: Number One, when Lilly reports that 21 adverse event, they don't make any causal relationship 22 themselves about whether or not the adverse event is causally 23 related to injection of Prozac; correct? 24 A. If you're specifically talking about reporting 25 to the FDA, the FDA excludes causality assessments, but that's 96 1 not true around the world, as you know. 2 Q. Yeah. We'll talk about England and forms and 3 Europe and forms -- CEANS (phonetic) -- in a minute. But when 4 we're talking about this wave of adverse events, the report is 5 based on, in most instances, a doctor's experience with the 6 drug? 7 A. Yes, sir. 8 Q. And you were getting a lot more of these in 1990 9 than you had been before; is that right? 10 A. Yes, sir. There's a big increase in the 11 frequency. 12 Q. Of course, in 1990, there was a big increase in 13 the number of people taking Prozac, too, wasn't there? 14 A. Yes, sir. But we adjust for that as a 15 denominator, and even with that adjustment there still was a 16 big increase in adverse-event reporting. 17 Q. Regardless of that, the answer to my question 18 is, yes, there was a large increase to the number of people 19 being exposed to Prozac in 1990, wasn't there? 20 A. Yes, sir. 21 Q. And it was being exposed to a larger number of 22 people because it was on the market at that time, wasn't it? 23 A. Surely, yes. 24 Q. And it had a -- there wasn't any -- the 25 postmarketing experience has the advantages over the clinical 97 1 trial experience in that there's a larger number of people, 2 Number One? 3 A. Yes, sir. 4 Q. And, Number Two, the clinical trial experience 5 is a controlled test to a large extent, isn't it? 6 A. Yes, sir. 7 Q. In other words, Lilly determines by virtue of 8 the protocols who's going to be in a clinical trial and who's 9 not going to be in a clinical trial? 10 A. Yes, sir. 11 Q. But that's not what happens in actual practice 12 in the real world of a drug. There's going to be a lot of 13 people that are exposed to the drug that might not have been 14 included in a clinical trial; correct? 15 A. That's correct, sir. 16 Q. So you're going to get a broader base of people? 17 A. Yes, sir. 18 Q. Not only in numbers but in varieties of severity 19 of depression and ages, gender, things of that nature? 20 A. Yes, sir. 21 Q. Let me hand you Plaintiffs' Exhibit 85, -- 22 A. Thank you. 23 Q. -- Doctor Thompson, and ask you if you can 24 identify that document. 25 A. This is an E-mail message that I wrote two 98 1 minutes after the one we've just been looking at. 2 MR. SMITH: We would offer Plaintiffs' 85, Your 3 Honor. 4 MR. FREEMAN: No objection, Judge. 5 JUDGE POTTER: Be admitted. 6 SHERIFF CECIL: (Hands document to jurors). 7 Q. Exhibit 85 is directed to Doctor Weinstein, is 8 it not? 9 A. Yes, sir. 10 Q. And, as you said, it's two minutes later than 11 Exhibit 86? 12 A. Yes, sir. 13 Q. And it's on the same subject, is it not? 14 A. Yes, sir. 15 Q. You say there, "I'm concerned about reports I 16 get where UK attitude toward Prozac safety"? 17 A. Yes, sir. 18 Q. And in all honesty, you didn't feel that the UK 19 was adequately attuned to being on top of these adverse-event 20 reports; is that correct? 21 A. As I explained before, it wasn't a concern 22 there, it wasn't a concern with their regulators, and I wanted 23 them to be sure that they understood that we were really 24 concerned about it and, therefore, they ought to pay special 25 attention to it. 99 1 Q. You say, "Leber suggested a few minutes ago 2 using the CSM data base to compare Prozac aggression and 3 suicidal ideation with other antidepressants in the UK." 4 A. Yes, sir. 5 Q. And you're talking again about Paul Leber? 6 A. Yes, sir. 7 Q. The head of the division at the FDA that 8 approved that product. 9 A. Yes, sir. 10 Q. You say in Exhibit 86 -- do you still have that 11 in front of you, Doctor Thompson? 12 A. Yes, sir; I do. 13 Q. You say that you had talked to Paul Leber a 14 couple of times in the last couple -- twice in the last 15 several days? 16 A. Yes, sir. 17 Q. Now, did you have another conversation with him 18 the morning of February 7th, 1990? 19 A. It's a little late for him to be calling me and 20 two minutes is awfully short time, so my guess is that it was 21 sometime earlier that morning. 22 Q. You're probably referring to one of these 23 earlier conversations or earlier that morning? 24 A. It was probably earlier that morning. 25 Q. You say, "Leber suggested a few minutes ago that 100 1 we using the CSM data base to compare Prozac aggression and 2 suicidal ideation with other antidepressants in the UK." CSM 3 data base, CSM is what, sir? 4 A. Committee on the Safety of Medicines. And this 5 is really an advisory group which advises the regulatory 6 authority in the UK about the regulation of drugs. 7 Q. All right. Would that be similar to the 8 Commission A advisory authority in Germany? 9 A. Yes, sir. I think it's very similar. 10 Q. And they had a data base at that time 11 concerning -- would it be adverse events of aggression and 12 suicidal ideation in connection with Prozac? 13 A. Let me explain it because we already talked 14 about the fact that in the U. S. most adverse-event reports 15 come from manufacturers like Lilly. And remember earlier I 16 said that in the UK, for example, most of those reports come 17 directly from practitioners. That system is called, slang, 18 the yellow-card system and the physicians in the UK are 19 particularly trained and encouraged to report adverse events 20 on all drugs; it has nothing to do with Prozac specifically. 21 And so the yellow-card system is another way of collecting a 22 large number of adverse-event reports. And the reason that 23 Doctor Leber was particularly interested in using it was he 24 thought that the U. S. reports were contaminated -- and I use 25 that word carefully -- by the press discussion of the Teischer 101 1 article and that, therefore, if we were able to quickly go to 2 the UK and look at adverse events that preceded the Teischer 3 article, we'd be able to look at how many reports had been 4 coming in on not just Prozac but all the other antidepressants 5 to see if there was a difference. 6 Q. Why not do that in the United States? 7 A. Well, we were doing that already, looking at the 8 U. S. reports that we had access to. Doctor Leber, of course, 9 has the similar data base that you talked about earlier, the 10 SRS, or whatever, at the FDA. They were already doing that. 11 Q. Was the CSM data base examined, as far as you 12 know, -- 13 A. Yes, sir. 14 Q. -- to make this comparison? As mentioned here 15 that Leber suggested a few minutes ago we using the CSM data 16 base, was that done, sir? 17 A. Yes, sir. It was done through one of the 18 professors in the UK who is an expert in this area. 19 Q. All right. But Lilly didn't do that, or did 20 Lilly hire that expert? 21 A. We hired the expert just like you talked about 22 before. 23 Q. Okay. You go on to say, "Although he is a fan 24 of Prozac," he meaning Doctor Leber? 25 A. Yes, sir. 102 1 Q. Is a fan of Prozac? 2 A. Yes, sir. 3 Q. Doctor Leber was a fan of Prozac at that time? 4 A. He told me he thought it was the best CNS drug 5 that they had approved and it was probably going to save more 6 lives than any other. I call that a fan. 7 Q. Do you know how long he had been a fan of 8 Prozac? 9 A. Well, I think after he beat us up on the safety 10 update and we responded with all the analyses that he wanted 11 and he really got into the data in great detail was when he 12 began to tell me very positive things about the drug. 13 Q. My question was do you know how long, not why, 14 but how long he had been a fan? 15 A. I don't remember the exact date of the first 16 safety update of the drug. It was something like '86 or '87, 17 and you know that date better than I. 18 Q. It says, "He believes a lot of this is garbage"? 19 A. Yes, sir. 20 Q. Did he use that term? 21 A. Yes, sir. 22 Q. Okay. So, Paul Leber, in February 1990, was 23 referring to reports of suicidal ideation and aggression and 24 murder as garbage? 25 A. Scientific quality thereof. 103 1 Q. He used the term garbage? 2 A. Yes, sir. 3 Q. You say -- but you go ahead and say, "He's 4 clearly a political creature and will have to respond to the 5 pressures." Correct? 6 A. Yes, sir. Absolutely. 7 Q. And then you go on and say, "I hope Patrick 8 realized that Lilly can go down the tubes if we lose Prozac, 9 and just one event in the UK can cost us that." Correct? 10 A. Yes, sir. 11 Q. Now, when you say "lose Prozac," what are you 12 referring to there, sir? 13 A. That the drug might be withdrawn from the 14 marketplace or have a very bad black box put on the label or 15 be damaged some other way. 16 Q. Well, if Paul Leber in February of 1990 was of 17 the opinion already at this time that this was a lot of 18 garbage, how were you going to lose Prozac? He's the head of 19 the division that approved it, Doctor Thompson. 20 A. Well, first of all, there are many other 21 regulators. Remember, we market this drug in 75 countries 22 that might take action against the drug, and it could be that 23 reports would come in that would put enough pressure on the 24 FDA that they would do something that's either right or wrong. 25 Q. Well, were there instances where the FDA had 104 1 responded to pressure and done something wrong up to that 2 point, Doctor Thompson? 3 A. They don't respond to pressure other than -- in 4 my opinion, other than doing a lot of investigation and having 5 a lot of hearings, I don't think they're very responsive to 6 pressure. But they get called up before Congress and beaten 7 on all the time. 8 Q. They did in connection with Norflex, didn't 9 they? 10 A. I don't really know. Did they? 11 Q. Yeah. Norflex. 12 MR. FREEMAN: Your Honor, you've already ruled 13 that out. 14 JUDGE POTTER: I don't know exactly what we're 15 talking about. 16 (BENCH DISCUSSION) 17 MR. FREEMAN: He's talking about admitting an 18 earlier drug, Norflex, and you've already ruled this out as to 19 the relevancy in this case. 20 JUDGE POTTER: Let me hear Mr. Smith tell me 21 what he was going to ask. 22 MR. SMITH: They were called on the carpet to 23 testify before Congress and he opened the door. And I called 24 him on the carpet in connection with Norflex, a Lilly drug, 25 and adverse events that happened outside the United States. 105 1 JUDGE POTTER: Well, what we're dealing with is 2 a collateral matter. If I remember the dates right, we're 3 talking about something in the late '70s, early '80s. 4 MR. SMITH: '84. Same time as this drug. 5 JUDGE POTTER: I'm sustaining the objection. 6 Q. You say that Lilly can go down the tubes if you 7 lose Prozac. Was that really your opinion at the time, Doctor 8 Thompson? 9 A. I thought this was one of our three leading 10 drugs and that if it got badly damaged that it would seriously 11 hurt the reputation of the company. I don't think I meant the 12 company would go out of business, but it would seriously hurt 13 us, both scientifically and financially. 14 Q. That's my question. Did you think that Eli 15 Lilly and Company would go out of business at that time? 16 A. No, sir; I didn't mean that. 17 Q. But your position in February of 1990, at that 18 time, was that if something happened to Prozac, that it would 19 be serious to Lilly as a company and to Prozac as a drug? 20 A. Yes, sir. 21 Q. Had you, Doctor Thompson, in any of those 22 conversations up to February 7th, 1990, with Doctor Paul 23 Leber, advised him that earlier the German government had 24 raised questions in connection with Prozac and suicidal 25 ideation and activation? 106 1 A. I don't remember the timing specifically. I 2 remember talking at the time we discussed the huge safety 3 update which was bigger than the NDA. I remember that we went 4 through the adverse events that had been fatal. So to the 5 extent that there were a couple of successful suicides, I know 6 that we discussed that with Doctor Leber specifically, but in 7 all honesty, they had looked at all those data and that was 8 just not a major concern of the FDA. 9 Q. But my question was, you know, you said that 10 Doctor Leber was a fan of Prozac and that he thought this 11 criticism of Prozac was garbage, in his own words. 12 A. At this time. 13 Q. My question to you is, up until that time, had 14 you told Doctor Paul Leber of the FDA that the German 15 government had raised, as early as 1984, these same questions 16 linking Prozac to suicide and activation and violent, 17 aggressive behavior? 18 A. Well, the answer is, I guess, yes, in the sense 19 that that was included in the annual IND reports. 20 Q. I'm not asking you what was included in the 21 reports. I'm asking you, since you were talking with him, if 22 you told him that this issue had been raised by the German 23 government six years earlier. 24 JUDGE POTTER: That's the same question. Go 25 ahead and answer it, sir. 107 1 A. Well, the answer is in the sense that a 2 submission from my staff to Doctor Leber and his staff is a 3 communication, he had the data, he knew of it. I can't recall 4 what words went into these conversations whether that came up 5 or not. I honestly can't remember. 6 MR. SMITH: Your Honor, I'd object to the 7 question as nonresponsive; my question simply was if he told 8 Doctor Leber. 9 JUDGE POTTER: He's answered your question, Mr. 10 Smith. 11 Q. And the answer is that you don't know but you 12 think that your staff made his staff aware of it? 13 A. No. You said communication. A communication 14 occurred for sure; whether words were exchanged on the 15 telephone with Doctor Leber at that time, I can't remember. I 16 don't remember the details of the conversations. 17 Q. You can remember the details that Doctor Leber 18 felt like that this criticism was garbage. 19 A. Well, I wouldn't be able to remember that except 20 you kindly jogged my memory with this memo. 21 Q. And you can remember the details that Doctor 22 Leber was a fan of Prozac? 23 A. Yes, sir. 24 Q. You were talking to him on the phone? 25 A. Yes, sir. 108 1 Q. But is it your testimony here that you can't 2 recall whether or not in any of these phone conversations up 3 to February of 1990, you told him that the German government 4 had raised these issues? 5 A. Mr. Smith, clearly the phone calls had to do 6 with suicidality and violence. Clearly, we talked about all 7 the data we had. Clearly, I knew that they had all the 8 questions from the Germans and the analysis we had done on the 9 subject. Whether the words came out of my mouth that said, 10 "Hey, Doctor Leber, remember the BGA questions," or not, I 11 can't remember, but that clearly was the focus of the phone 12 calls that we had. 13 Q. I understand that the question was the -- that's 14 my point. The phone calls were in connection with this issue. 15 I'm just wondering if you told him that this issue had been 16 raised back early in 1984. 17 A. I don't know whether I reminded him to go look 18 in that submission or not. 19 Q. That submission, you felt at the time that you 20 submitted that safety update or the response to the BGA, had 21 settled the issue, hadn't it? 22 A. No. We were continuing to look very carefully 23 at this among the other safety issues that we had raised and 24 regulators around the world had raised. It's just this wasn't 25 a big concern because the data spoke so eloquently to the fact 109 1 that we didn't have a problem. 2 Q. The data spoke eloquently that you didn't have a 3 problem? 4 A. That's right. 5 Q. And you're talking about the clinical trial 6 data, are you not? 7 A. And the postmarketing data up to the point of 8 the Teischer article. 9 Q. And the product had been on the market -- it was 10 approved in December of '87, so the product had been on the 11 market for two years in the United States? 12 A. Yes, sir. 13 Q. Was the product on the market in Germany at this 14 time? 15 A. I don't really remember when it was approved in 16 Germany. 17 Q. Well, it was approved in December 1989 in 18 Germany; this is dated February 7th. December 1989 in Germany 19 Prozac was approved as Fluctin in Germany. This memo was 20 dated February 7, 1990. Do you know if Prozac was actually 21 being marketed in Germany by that time? 22 A. Only by what you just told me, sir. 23 Q. Well, did you tell Doctor Leber in any of these 24 conversations up to February 7th, 1990, that the German 25 package insert in this connection of patients with a risk of 110 1 suicide advised that concomitant sedatives should be used? 2 A. I don't think that's exactly the way I would 3 translate the label, but he had the label or a digest of the 4 label because we had submitted that at one of the safety 5 updates, either to the approval board or the approval letter. 6 Q. My question simply was did you tell Doctor Leber 7 in any of these phone conversations up to that time about the 8 contents of the German label? 9 A. Mr. Smith, I'm sorry. I can't recall that 10 detail. 11 JUDGE POTTER: It's the September 9th? Exhibit 12 68. 13 MR. SMITH: September 9 approval letter, Exhibit 14 68. 15 I want to give you a copy so we can refer to it 16 together. 17 A. Yes, sir. 18 Q. It's the approvable letter from the Department 19 of Health, Education and Welfare, the FDA dated September 9th, 20 1987, is it not? 21 A. Yes, sir. 22 Q. And you're addressee on this letter, are you 23 not? 24 A. I'm sorry. Where is that? 25 Q. Look on page -- well, it would be 65 1772, lower 111 1 right-hand corner of the page, Doctor W. L. Thompson. 2 A. The page numbers I've got are numbered from 284 3 to 308. I'm sorry. 4 Q. We may be looking at two exhibits. Right here, 5 you're addressee, aren't you, Doctor? 6 A. I don't think I have that, sir. 7 JUDGE POTTER: Maybe I gave you the wrong thing, 8 Mr. Smith. 9 MR. SMITH: Can I show this to Doctor Thompson? 10 I know we're talking about the same thing. I 11 just want to make sure. I think we may have exhibits that 12 aren't the same. It's the September 9th, '87 letter from the 13 FDA addressed to Doctor Talbott. Then Page 2 says September 14 11th on the top of it, and you're copied in as a cc. 15 A. I believe that to be an internal Lilly memo 16 that's probably out of order, and this may have been the cover 17 by which they transmitted to me this. But you see what it 18 says up here, it's in regard to the letter of 9-9 -- that's 19 probably that one, the submission of 9-11 and the letter of 20 9-11, but I don't think those two are in what you gave me. I 21 think only the first part was there. 22 Q. Okay. Do you recognize Page 2 as being part of 23 the approvable letter? 24 A. Yes, sir. 25 Q. All right. Where they find -- 112 1 MR. FREEMAN: Could we have a copy of what we're 2 talking about? 3 MR. SMTIH: That's what I can't find. I can't 4 find a copy. 5 MR. FREEMAN: Could we just see it? 6 JUDGE POTTER: Let Mr. Freeman look at what 7 you've got. I think there may be some pages out of order or 8 something. Mr. Smith, you want to work from that one? That's 9 the original. 10 MR. SMITH: Yeah. It doesn't have that one page 11 I did, but it's got Page 2. 12 MR. FREEMAN: This is Page 2. 13 JUDGE POTTER: All right. He's going to work 14 from -- 15 MR. SMITH: Here's the original. I'm going to 16 give that to Doctor Thompson. 17 JUDGE POTTER: All right. It's already been 18 introduced. The jury has the same thing. 19 Q. You're familiar with the approval letter, aren't 20 you, Doctor Thompson? 21 A. Yes, sir; I am. 22 Q. And on the top of Page 2 it says, "We find the 23 application approvable;" correct? 24 A. Yes, sir. 25 Q. But they want some more information from you, 113 1 don't they? 2 A. Yes, sir. 3 Q. And they -- if you'll look into the second full 4 paragraph there, Item 7 says, "Your submission of a summary 5 reviewing all actions taken or actions now pending before 6 foreign national drug regulatory agencies involving 7 fluoxetine." Do you see that? 8 A. Yes, sir. 9 Q. Eight is, "Your submission of copies of all 10 drafts and/or approved foreign labeling, with English 11 translations where necessary"? 12 A. Yes, sir. 13 Q. And 9, "A review of and report on the archival 14 domestic and foreign literature discussing any findings that 15 identify actual or potential risk associated with the use of 16 fluoxetine;" correct? 17 A. Yes, sir. 18 Q. At that time in September of '87, are you 19 confident that the United States Food and Drug Administration 20 had this -- all foreign labeling information and all foreign 21 regulatory information before them? 22 A. Well, not before this letter, but I'm confident 23 that we fulfilled all the requirements in response to the 24 letter, but it took months to put all this together. 25 Q. But before that time, is it your testimony that 114 1 the FDA probably didn't have all of the information concerning 2 foreign regulatory activities? 3 A. Well, regulatory activities is not a very 4 precise term. There's several things that happened. One is 5 they changed the FDA regulations, so requirements on reporting 6 on foreign regulatory activities was something that was 7 relatively new. Secondly, in their translating of that term 8 to me, they were very explicit about what they wanted and 9 didn't want about what was going on with foreign regulators. 10 But it's my understanding that all the analysis on this 11 particular issue about suicidality and violence that we had 12 sent to the BGA in fact had been sent to the FDA. I think it 13 was with the IND annual report in 1985. 14 Q. Okay. So is it your testimony here that you 15 wouldn't have needed to send anything else to the FDA in 16 connection with the issue raised by the German government 17 because you had already sent it back in 1985? 18 A. Oh, no, sir. I think that a huge response was 19 made to this letter. I wasn't asserting that at all. I was 20 asserting that they already had some of the information; there 21 was a lot more that was required here. They go on for pages 22 and pages describing how to do the analysis. So we had a lot 23 of work to do to provide them with those data. 24 Q. Well, so can we say, then, that in September of 25 1987, the FDA did not or did have all the BGA issues? 115 1 A. I think that at the time they sent this to us, 2 before we responded to it, they were aware of the BGA being 3 concerned about suicidality and they had in fact a great deal 4 of data from us in terms of the analyses of the data that we 5 had been doing on that specific issue, but that's not 6 asserting that every single thing that we knew as of the date 7 of this letter was in the hands of the FDA. 8 Q. Okay. You just don't know what was in the hands 9 of the FDA concerning this issue raised by Germany on 10 September 9, 1987? 11 A. Well, I've said what I know they did have. I 12 don't know -- because the submissions are generally not made 13 on a daily basis; they're made on an annual basis. And I 14 don't know, for example, what was in the '86 IND report or the 15 '87 IND report, for that matter. But this letter requests us 16 to provide them with a whole bunch more information, which we 17 complied with. 18 Q. All right. Specifically, on Page 7, there is 19 even more language concerning what you're supposed to provide, 20 is there not? 21 A. Yes, sir. 22 Q. It says we require a review -- it's under 5, 23 Report on Actions taken by other National Drug Regulatory 24 Authorities. "We require review of the status of all 25 fluoxetine actions taken or pending before foreign regulatory 116 1 authorities. Approval actions can be noted, but we ask that 2 you describe in detail any and all action taken that have been 3 negative, supporting a full explanation of the views of all 4 parties and the resolution of the matter." 5 MR. FREEMAN: Supplying a full explanation, I 6 think. 7 JUDGE POTTER: Isn't that what he said? Go 8 ahead, Mr. Smith. 9 A. Supplying is correct and you read it correctly; 10 yes, sir. 11 Q. All right. Had you done that in connection with 12 the German issue on September 9, 1987. 13 A. At the time we received this? 14 Q. Yeah. 15 A. No. I wouldn't assert we had fulfilled the 16 request at the time they sent us the request. 17 Q. Well, if you had sent them your entire response 18 to the BGA, wouldn't they have already had all of this 19 information available to them? 20 A. Well, I know that they got in -- I think it was 21 in 1985 that the IND annual report they got a copy of the 22 analysis on suicidality we sent to the BGA. If you recall, 23 the BGA raised about 20 issues, and they said the most 24 important issue was a question of lung and eye changes. I 25 don't know what they sent the FDA on that issue because I 117 1 haven't looked it up. And, in fact, a lot of things must have 2 happend between 1985 and September 9, 1987. This was also the 3 first time we had ever gotten a request like this from the FDA 4 because they changed their regulations. This was a new 5 requirement that we'd never seen before. So I can't possibly 6 assert that we had already fulfilled all that they required in 7 this document. We spend months putting together the response 8 to this document. 9 Q. In response to the approvable letter? 10 A. Yes, sir. 11 Q. All right. 12 At this time, Your Honor, we have Plaintiffs' 13 Exhibit 89, which is, by way of explanation, the approvable 14 letter sent by the FDA with the package insert included. 15 Let me give that to you, Doctor Thompson. 16 A. Thank you, sir. 17 SHERIFF CECIL: (Hands exhibit to jurors). 18 MR. SMITH: We offer Plaintiffs' Exhibit 89. 19 MR. FREEMAN: No objection. 20 JUDGE POTTER: Just for my education, what's the 21 difference between this and whatever the other one was. 22 MR. SMITH: This has the package insert 23 information on the back of it and has Doctor Thompson's notes 24 on it. 25 JUDGE POTTER: Okay. 118 1 MR. FREEMAN: Judge, I think I should point out 2 the letters are identical except for Doctor Thompson's notes, 3 but the package insert is also on the other exhibit. 4 JUDGE POTTER: Okay. Well, just so the jury 5 knows, this is the same as what you had before except it's got 6 some handwritten notes on it. Go ahead. Be admitted. 7 Q. Can you identify Plaintiffs' Exhibit 89, Doctor 8 Thompson? 9 A. Yes, sir. As you asserted, it's another copy of 10 the approval letter, and it contains notes at least most of 11 which I wrote. 12 Q. And along with that is the proposed labeling? 13 A. Yes, sir. I think that's really part of the 14 approvable letter itself. 15 Q. And that starts on Page 3 -- PZ 364 2748; right? 16 A. Yes, sir. 17 Q. And these continue to be your notes in the 18 margins? 19 A. Most of them are. 20 Q. All right. Turn to Page 364 2749, under 21 Metabolism? 22 A. Yes, sir. 23 Q. There's writing out there that says "Oops." 24 A. Yes, sir. 25 Q. What does that refer to? That's your note, 119 1 isn't it? 2 A. That is my writing. We obviously had not 3 explained the data that we had, because you notice this is a 4 parenthetical note to the firm from Bob Temple, and he's 5 talking about we inferred the insignificance of renal 6 excretion and so forth; is there any direct evidence on the 7 proportionate dose actually excreted. I thought we had that 8 data and it had been submitted and maybe we didn't explain it 9 well enough that they understood it. 10 Q. All right. Then go back to -- go on to 11 Page PZ 364 2751. 12 A. Yes, sir. 13 Q. Up at the top right-hand side of the page, "Do 14 we accept this," is that what it says? 15 A. Yes, sir. 16 Q. And that has to do with what, sir? 17 A. It's talking about what we call the kinetics of 18 a drug, which means the time course of the drug after you take 19 a pill: How long does it take to get into the bloodstream, 20 how long does it take to get into other parts of the body, how 21 long does it take to be metabolized or changed by the body and 22 how long does it take to be excreted by the body. And, in 23 essence, what it says is here's a drug with a long half-life. 24 It takes days and days to get rid of fluoxetine and its 25 metabolites. And nonlinear disposition -- that's a little 120 1 arcane, but what it means is if you double the dose, you may 2 get more than double the effect or the concentration. 3 It says, "A single-dose study is not adequate to 4 rule out the possibility of altered kinetics -- that's the 5 time course -- in the elderly, especially if they have 6 systemic illness." As we get older, we lose kidney function; 7 it actually starts at about age 20. So a person over the age 8 of 65 has less kidney function than a person your age and, 9 therefore, if a drug is excreted by the kidney, you worry 10 about the fact that it may have a greater effect, a greater 11 duration of action in an old person. And what he's saying is 12 that we had done studies of a single dose, giving it to people 13 over the age of 65, but in Doctor Temple's opinion, we needed 14 to do multiple dose studies in that population to address this 15 issue. 16 Q. Okay. Then your notation out there beside that 17 says, "Do we accept this." 18 A. Yes, sir. 19 Q. Now, does that mean -- what does that mean? 20 A. Well, this was probably -- I was addressing that 21 more to Doctor Bergstram and Doctor Lemberger, who are the 22 experts in this area, saying don't we feel that we in fact 23 have enough information and that we don't need to do anything 24 else, or do we accept it, do we agree that we do need to do 25 additional stuff. 121 1 Q. But are you accepting this language in the 2 package insert? Is that the question, whether or not to 3 accept this language in the package insert? 4 A. Well, both whether or not to go back and argue 5 that the language ought to be changed or do we need to do some 6 additional research to address the question. 7 Q. Okay. Then if you look under Indications and 8 Usage on that same page, in the -- the next notation you have 9 is in connection with, "The antidepressant action of Prozac in 10 hospitalized depressed patients has not been adequately 11 studied." And what is your notation there beside it? 12 A. I think it says, "Must we say -- perhaps 'it' -- 13 this way." 14 Q. All right. Then under that, it's talking about 15 effectiveness of Prozac in long-term use, and you say, "Again, 16 this is more negative than our data -- 17 A. Warrant. 18 Q. -- warrant." All right. So you're making 19 comments concerning the substance of this package insert; is 20 that right? 21 A. Yes, sir. I had just seen this for the first 22 time, and the purpose of this was to make comments to my staff 23 to say is this right; do we buy into this; do we need to do 24 something differently; do we go argue with the FDA about it. 25 Q. All right. Then on Page 5, on the top of that 122 1 in connection with rash, you have a notation, "Very 2 reasonable." Is that right? 3 A. Yes, sir. 4 Q. Then under -- on Page 6, under Precautions, 5 General, where it says Seizures, it's talking about 12 6 patients among 6,000 evaluated developed or experienced 7 convulsions, and then what is that notation you've got 8 underneath that? 9 A. Well, to the right or underneath? 10 Q. Underneath? 11 A. "We don't think 12 had true seizures." 12 Q. All right. Then to the right of it you've got a 13 "Whew," W-H-E-W, and exclamation mark? 14 A. Whew. 15 Q. Right. What did you mean by that? 16 A. Well, this had been a particular concern of ours 17 because one of the major side effects of other antidepressants 18 is the fact that they will cause seizures, especially in 19 overdose. So we had been watching very carefully to see if we 20 had any evidence if this drug would cause seizures either in 21 patients with epilepsy or patients on other drugs or just 22 patients in general. And I thought that was a very reasonable 23 reading of the data; actually, we thought it was less than 12 24 and they should have said that we had less trouble than other 25 drugs, but they didn't know it at the time; we know it now. 123 1 Q. But the fact is that this had been language that 2 you had submitted to the FDA and they had approved on seizures 3 in connection with Prozac? 4 A. I don't think that's correct. I don't know 5 what -- I mean, they write the proposed label. I don't know 6 what we submitted; we submitted all the data. 7 Q. You submitted the proposed label to the FDA. 8 A. We did? 9 Q. Yes. 10 A. When did we do that? 11 Q. Back as early as 1983, when you submitted your 12 NDA. 13 A. Oh. It's part of the New Drug Application, 14 sure. 15 Q. Isn't part of the process your proposed label to 16 go with Prozac; right? 17 A. Yeah. But what you get back from the FDA never 18 looks very much like what you tell them. 19 Q. And here it looked like what you told them; 20 right? 21 A. I don't know what we submitted, sir, to be 22 honest with you. 23 Q. All right. 24 A. Again, I'm saying "whew" because at least it's 25 not bad, although many people at Lilly would say that we 124 1 should have gotten a statement that we had less problems than 2 this during the process. 3 Q. You said "whew" there because at least it's not 4 bad; right? 5 A. Right. 6 Q. Okay. Turn to Page 7 under Suicides. You say 7 "whew" there. Is that because at least it's not bad? 8 A. Well, I think it's the same kind of statement 9 that's made about all the other antidepressants, and I agreed 10 with that. 11 Q. It says, "The possibility of a suicide attempt 12 is inherent in depression and may persist until significant 13 remission occurs. Close supervision of high-risk patients 14 should accompany initial drug therapy. Prescriptions for 15 Prozac should be written for the smallest quantity of capsules 16 consistent with good patient management in order to reduce the 17 risk of overdose." Correct. 18 A. Yeah. Even at that time we knew that overdose 19 was not going to be as big a problem as with the other drugs 20 but, in general, I thought that was a very fair reading of the 21 problem because we were very concerned about the fact that 22 depressed people tend to kill themselves. 23 Q. And you were concerned about what the package 24 insert in the United States would say? 25 A. Absolutely. 125 1 Q. Did you know at this time in September of 1987, 2 when you had submitted this proposed labeling, that the 3 German -- that your employees in Germany were suggesting that 4 there be labeling requiring use of sedatives in connection 5 with agitated and suicidal risk patients? 6 MR. FREEMAN: Objection, Your Honor. The German 7 label says "may" use, not required to be used. 8 A. There are two problems I've got with your 9 assertion. 10 JUDGE POTTER: Go ahead and answer. 11 A. One is I think it's unfair to characterize that 12 it's all the German; you didn't say all, but there was 13 certainly one person in Germany who had suggested that, and 14 the BGA had slightly different wording. And the second thing 15 is that, as Mr. Freeman so kindly put in, the fact that it 16 doesn't say that you ought to do that, it says you may. We in 17 fact had discussed that with the FDA. 18 MR. SMITH: Your Honor, I'm sorry. I thought I 19 had my documents in order, but I don't. 20 JUDGE POTTER: We're going to take one recess 21 this afternoon anyway, and maybe this is a good time to do it. 22 I've been sending out notes to the maintenance 23 man, folks. I don't know what more I can do. I thought I 24 felt a change a few minutes ago to cooler, so maybe it will be 25 better. 126 1 As I mentioned to you-all, do not let anybody 2 communicate with you about this case or any topic connected 3 with this case. Do not discuss it among yourselves or form or 4 express opinions about it. We'll take a 15-minute recess. 5 (RECESS) 6 JUDGE POTTER: Mr. Smith and Mr. Freeman, here's 7 a note from a juror. 8 MR. FREEMAN: We have the most prolific crowd in 9 asking questions I've ever seen. (Examining note) We're 10 talking cats again. The question is why Lilly didn't do REM 11 studies on humans presently. 12 JUDGE POTTER: Are you going to cross-examine? 13 Can I depend on one of you asking that question before we get 14 through? 15 MR. SMITH: I'll ask it right now. 16 SHERIFF CECIL: The jury is now entering. 17 The jurors are present. 18 JUDGE POTTER: Please be seated. 19 Doctor, I'll remind you you're still under oath. 20 Mr. Smith. 21 Q. Doctor Thompson, earlier we were talking about 22 REM sleep and there was an early publication in 1978 or '77 by 23 Doctor Slater in connection with REM sleep in cats. And 24 you -- correct? 25 A. Yes, sir. 127 1 Q. And you already I believe earlier today 2 testified that there are some experts doing REM sleep studies 3 now in humans to determine levels of serotonin; is that right? 4 A. No, sir, not quite. What we're looking at is a 5 marker of what patients might respond to Prozac or other drugs 6 versus those that don't respond. 7 Q. Why wasn't this study done earlier? 8 A. Well, it was done fairly early and, as a matter 9 of fact, in one of the documents that we saw earlier this 10 morning from the BGA, I think one of their questions was that 11 we didn't have enough sleep studies. I've forgotten whether 12 we had -- I don't know how many we had at the time of the NDA, 13 but the Germans are very much into physiology and measuring 14 things very precisely. So REM, or rapid-eye-movement sleep, 15 is a big issue in Germany; whereas, in the United States until 16 recently it's just been one of the things that people have 17 observed but no one has paid much attention to it. What I 18 said Lilly is now doing is not generally accepted in the 19 scientific literature that you can distinguish people who 20 respond to drugs by REM sleep studies. We've been doing that. 21 I don't think we've even published those data yet. We're 22 using Prozac as well as other neuroantidepressants in those 23 studies. 24 Q. When did you start doing those studies on REM 25 sleep in humans? 128 1 A. Well, in terms of Prozac, just making 2 observations of rapid-eye-movement sleep, it goes back to 3 around the time I was coming to the company, but those were 4 really just to observe what happened to rapid-eye-movement 5 sleep rather than -- remember, you and I were discussing can 6 you distinguish a patient that ought to get Prozac from a 7 patient who shouldn't, and I was saying, to my knowledge, 8 that's the only test I know of today that one can use. But 9 it's not even accepted yet -- I'm not even sure our -- I know 10 a lot of our data is not in the scientific literature yet. 11 Q. If those studies had been conducted along early 12 on in the Prozac research, why weren't those studies published 13 and why hasn't there been some conclusion reached in 14 connection with those studies? 15 A. I want to distinguish the fact that they were 16 all looking at rapid-eye-movement sleep, but they really were 17 looking at two different questions. The studies that were 18 done early were just looking at patients who were treated with 19 Prozac or tricyclics and, as with other antidepressants, what 20 you see is that the abnormality in rapid-eye-movement sleep is 21 partly, at least, corrected by the drugs in many of the 22 patients. Well, you know, that's sort of a ho-hum. Yeah, 23 here's another one of those drugs and, yeah, it does the same 24 kind of thing in people. There's no big excitement there. 25 Now, what I was just telling you, however, is 129 1 very exciting, because we have absolutely no idea how to tell 2 which patient with depression to treat with drugs, or which 3 drug, for that matter. And if, in fact, we could do this test 4 and say these two-thirds of people with depression because of 5 their rapid-eye-movement patterns ought to get drugs, but over 6 here we can tell the one-third that aren't going to respond, 7 that would be very significant, and that's the kind of thing 8 that we're doing now. But it's cutting edge; nobody's ever 9 done this before. 10 Q. Why wasn't it done earlier? 11 A. Well, maybe we didn't think of it. You have to 12 do the test on the patient who's depressed first, and then you 13 give them the drug to see whether they'll respond or not. So 14 it's not measuring the rapid-eye-movement response to Prozac; 15 what it's doing is saying here's some depressed people that 16 have more rapid-eye-movement changes than others; will that 17 distinguish people who will respond well to the drug from 18 those who won't. I don't think anybody had ever thought of 19 doing that until recently. 20 Q. Even though Prozac has been as a substance under 21 investigation by Lilly since the late 1970s, over 20 years? 22 A. Well, we've been using antidepressants since the 23 early 1950s, and I think sleep studies go back 25 or 30 years 24 with other drugs. 25 Q. All right. 130 1 A. They're very expensive, Mr. Smith. 2 Q. To do those studies? 3 A. Yes, sir. You normally have to take a patient 4 into the laboratory for -- usually it's more than one night, 5 probably. Somnography, I think it's usually four nights. 6 You've got to have a patient who's willing to go and sleep in 7 a hospital laboratory for two or three nights, got to have a 8 technician who's there the whole time. You have to monitor 9 their brain waves as well as their eye movements, then you've 10 got to analyze it. It's very difficult to analyze. You know, 11 it's just an expensive study to do. 12 Q. And nobody at Lilly has decided to expend that 13 sum to further investigate that area? 14 A. Oh, now, that's not fair, Mr. Smith. I said we 15 had done REM sleep studies back before the NDA; we're 16 pioneering it's use today in trying to distinguish the 17 patients that will respond to drugs, including some of our new 18 antidepressants. 19 Q. Well, are you not doing the study because of the 20 expense? 21 A. No, sir. We're doing the studies, because now 22 we're very excited that we may have a handle for the first 23 time on which patients will respond to therapy. All I'm 24 saying is, if you put this out into general practice, it may 25 be so expensive that in treatment of a depressed patient it 131 1 may not be practical to do five or ten thousand dollars' worth 2 of studies to decide how to treat them, rather than just 3 giving them a pill and seeing if they respond in three or four 4 weeks. 5 Q. Before we broke, we were talking about the 6 package insert in the United States in connection with Prozac 7 and those statements after Suicide; correct? 8 A. Yes, sir. 9 Q. It's on Page PZ 364 2754. 10 A. Yes, sir. 11 Q. And the language there to which you've written 12 "whew" is the language that is currently in the Prozac package 13 insert, is it not? 14 A. I think so. 15 Q. And it was the language in the Prozac package 16 insert in December -- in September and August 1989, was it 17 not? 18 A. Yes, sir. 19 Q. Let me hand you a copy of Plaintiffs' Exhibit 20 102, and ask you if you can identify that as being an early 21 proposal in connection with the German package insert. 22 A. I'm not honestly sure that I've seen this 23 document before, but it's dated -- at least pieces of it are 24 dated December 6 of 1989, and the cover memo is from Nick 25 Schulze-Solce to Allan Weinstein. 132 1 Q. And Alan Weinstein in December of '89 was 2 reporting to you, was he not? 3 A. I don't think so. Remember I said in '90, even 4 February of '90, that was somewhere around there he began to 5 report to me. 6 Q. Were you aware in December of 1989, that the -- 7 that Lilly was submitting to the BGA proposed package-insert 8 labeling information? 9 A. I really wasn't in the loop for how that 10 happened. I obviously knew that we were trying to get the 11 drug marketed in Germany and that we were submitting stuff to 12 the BGA, but I honestly didn't know the regulatory procedures 13 there. 14 MR. SMITH: We would offer Plaintiffs' Exhibit 15 102, Your Honor. 16 MR. FREEMAN: No objection. 17 JUDGE POTTER: Be admitted. 18 SHERIFF CECIL: (Hands exhibit to jurors). 19 Q. Turn to Page PZ 1341 402, Doctor Thompson. 20 A. Yes, sir. 21 Q. And as the cover letter says, "This is the 22 package insert for professionals for fluoxetine in Germany 23 after incorporation of the BGA changes." Correct? 24 A. Yes, sir. 25 Q. On Page 402, there is -- it has a heading 133 1 Precautions in Patients at Risk, does it not? 2 A. Yes, sir. 3 Q. Under that it talks about the metabolism of 4 Prozac by the liver, does it not? 5 A. Yes, sir. 6 Q. Then the next sentence says, "Fluoxetine does 7 not act generally sedating," does it not? 8 A. That's what it says. 9 Q. It also says, "Until the onset of the 10 depression-alleviating effect, the patients have to be 11 observed adequately. In patients with suicidal risk, 12 continuous observation and/or a generally sedating additional 13 therapy can be necessary. In patients suffering from 14 agitation or marked sleep disturbance, Fluctin has to be used 15 with special care," does it not? 16 A. Yes, sir. 17 Q. That is different from the United States 18 package-insert information, is it not? 19 A. Well, it's slightly different. 20 Q. Well, if you compare the two it's a lot 21 different, isn't it, Doctor Thompson? 22 A. I think the jury can read them as well as you 23 and I can. I can go into the philosophy behind them, if you'd 24 like. 25 Q. Is Prozac an activating antidepressant, in your 134 1 opinion? 2 A. I'd like an opportunity to provide the data on 3 which I'm going to answer that one yes or no, because that's 4 been a real point of issue. And some of us have said yes and 5 some of us have said no, and you've got to be real careful in 6 answering that. And I'll give you a yes or no, but I want to 7 make sure that we are talking about the same thing because, 8 first of all, the side effects to the drug differ in different 9 illnesses, so the side-effect profile in depression is 10 different than in obesity, bulimia, obsessive-compulsive 11 disease, and smoking cessation and so forth. I bet you want 12 me to talk about depression because that's what Mr. Wesbecker 13 had; is that right? 14 Q. Yeah. And I'm going to give you an exhibit that 15 we've been provided by your company, I think which was 16 authored by one of your psychiatrists there at your company. 17 A. You asked me and I told you earlier, I speak for 18 myself. 19 Q. I understand. I understand. 20 A. Can I finish answering your question? 21 MR. FREEMAN: Please. 22 JUDGE POTTER: Well, Mr. Smith? 23 MR. SMITH: I thought he had answered the 24 question. I'm certainly not going to give him the opportunity 25 to -- 135 1 JUDGE POTTER: Okay. Go on to your next 2 question. Ms. Williams, should we take a break? 3 JUROR WILLIAMS: No, thank you. I'm sorry to 4 bother you. 5 JUDGE POTTER: No, that's all right. Sometimes 6 people sound like they're in much more distress than they 7 really are and... 8 JUROR WILLIAMS: I have a tickling that just 9 won't quit. 10 JUDGE POTTER: All right. As long as it's just 11 a tickling and you're okay, we'll go ahead. All right. 12 JUROR WILLIAMS: Thank you. 13 JUDGE POTTER: All right. 14 Q. You've seen this paper written by Doctor Beasley 15 before, have you not? 16 A. Well, I've seen the publication itself. If it 17 is the same thing word for word -- I don't think I've seen 18 this particular draft of it, but I've seen the publication. 19 Q. All I know, Doctor Thompson, is it was given to 20 me as a paper authored by Lilly lawyers -- authored by Doctor 21 Beasley. 22 A. Well, I can't testify that it's from Doctor 23 Beasley and, again, I'll be glad to tell you what I remember 24 about his actual scientific publication, but I don't think 25 I've seen this before. I've seen a publication that addresses 136 1 this, for sure. 2 Q. Well, I think this is just a typewritten copy of 3 that publication, Doctor Thompson. You're familiar, of 4 course, as the chief scientific officer that this issue has 5 arisen? 6 A. Absolutely. 7 Q. And this was -- this Beasley article -- are you 8 speaking of the Beasley article that was published? 9 A. On activating and sedating adverse events, that 10 was published either '93 or '94 in either the Journal of 11 Psychopharmacology or the Journal of International 12 Psychopharmacology, and I'll look it up, if you'd like. 13 Q. Review that and see if it doesn't purport to be 14 the same article. 15 We would offer 70, Your Honor. 16 A. It doesn't have the illustrations I'm familiar 17 with, and some of the numbers are not the ones I'm familiar 18 with in that publication. In fact, I don't think this is word 19 for word the publication. But I've got the publication if you 20 want to talk about the publication. 21 JUDGE POTTER: First of all, is there an 22 objection to this exhibit? 23 MR. FREEMAN: Yes, sir. He's not familiar with 24 the exhibit. 25 Q. Well, let me ask you this, Doctor Thompson. Has 137 1 it ever come to your attention as the chief medical officer of 2 Eli Lilly and Company that a psychiatrist at Eli Lilly and 3 Company examined the clinical trial data to determine whether 4 or not Prozac is an activating or a sedating antidepressant? 5 A. Yes, sir. There's no person called the chief 6 medical officer, but as my current position I am aware. 7 Q. I apologize. Chief scientific officer? 8 A. I am aware, yes, sir. 9 Q. Has it come to your attention that a 10 psychiatrist has published or has studied the question of 11 whether or not Prozac is activating or sedating? 12 A. Yes, sir. 13 Q. And that he's examined the fluoxetine clinical 14 trial data? 15 A. Yes, sir. 16 Q. And that he considered in the activation 17 clusters, those items such as nervousness, anxiety, agitation 18 and insomnia? 19 A. Yes, sir. 20 Q. And he considered for the sedation cluster 21 somnolence and asthenia? 22 A. Yes, sir. 23 Q. And what is asthenia? 24 A. It sort of means feeling punk. It's not the 25 most specific term, but if you feel weak, tired, run down, 138 1 that would get classified as asthenia. 2 Q. All right. Did -- were you aware as the chief 3 scientific officer that one of your psychiatrists had 4 concluded that approximately 19 percent of patients might be 5 expected to report activation during acute therapy with 6 fluoxetine which was not present prior to therapy, which could 7 be attributed to fluoxetine in trials? 8 A. I wasn't aware of that specific statement, but 9 I'll be glad to address the data in great depth. 10 Q. Were you aware that he found in his examination 11 of the clinical trial data that 38 percent of the 12 fluoxetine-treated patients reported new activation, but 19 13 percent of the placebo patients also reported new activation, 14 nearly the difference of 19 percent attributable to 15 fluoxetine? Are you aware of that, sir? 16 A. No, sir; I'm not aware of that specific 17 assertion, and it depends on which data you look at. That's 18 why I was trying to address that. And, by the way, this is 19 not at all like the publication I was referencing. 20 Q. Okay. Well, maybe this is something that you 21 haven't seen. 22 A. I told you I haven't seen it. I can't even find 23 the author on it. 24 Q. It says here approximately 13 percent of the 25 patients might be expected to report sedation with fluoxetine; 139 1 right? 2 A. That's what it says, sir. 3 Q. Were you aware that this analysis of the 4 clinical trial data indicated, according to this psychiatrist, 5 that fluoxetine is activating relative to tricyclics, and 6 tricyclics are sedating relative to fluoxetine? 7 MR. FREEMAN: We earlier made an objection to 8 the document. 9 JUDGE POTTER: Approach the bench. 10 (BENCH DISCUSSION) 11 MR. FREEMAN: We earlier made the objection that 12 the Witness is not familiar with it. It doesn't show who the 13 author is or anything about it. He doesn't know anything 14 about the document and "are you aware" to state it as a fact 15 is not an appropriate line of questioning. The Witness is not 16 aware of any of it. 17 MR. SMITH: This is cross-examination and I'm 18 going to ask him what knowledge he has and what knowledge he 19 doesn't have. 20 JUDGE POTTER: Does anybody know what this thing 21 is? 22 MR. SMITH: Yes. I know what it is. It's the 23 article or the report written by Doctor Charles Beasley on 24 this issue and has been produced to us as an authentic 25 document by Lilly. 140 1 JUDGE POTTER: Mr. Myers, do you know what it 2 is? 3 MR. MYERS: That may be some work that Doctor 4 Beasley did, Your Honor, but I don't believe or I don't know 5 for sure that it's the same article to which Doctor Thompson 6 refers, and it seems to me if he doesn't know what it is, the 7 way to put it in is through Doctor Beasley. 8 JUDGE POTTER: Is everybody agreed that this 9 thing is going to come in at some time? 10 MR. MYERS: I don't know for sure, Judge. 11 That's just one that I'm not sure about. 12 MR. SMITH: This is the chief scientific officer 13 who said that Prozac is not activating, and he's got an 14 employee who's a psychiatrist who is reporting that it is. 15 I'm entitled to question him if he knows of these findings. 16 JUDGE POTTER: I agree with what you say, Mr. 17 Smith, but, again, the objection is you're stating as facts in 18 questions things that are not in evidence and things that at 19 this point we can't be sure are going to be in evidence. Has 20 anyone got a copy of the article? 21 MR. FREEMAN: Doctor Thompson has a copy of the 22 article, and it doesn't state what he's purporting to state. 23 It says in the majority of the people it's not activating or 24 sedating; a small percentage is both, but not otherwise. 25 MR. SMITH: Golly, Judge, they gave this to us 141 1 as being authentic. Doctor Beasley has testified he did this. 2 JUDGE POTTER: I can't tell. Where did this 3 thing come from? 4 MR. SMITH: Nancy? 5 JUDGE POTTER: Ms. Zettler, do you know what 6 this thing is? 7 MS. ZETTLER: It's Doctor Beasley's activation/ 8 sedation study. 9 JUDGE POTTER: Where did it come from? 10 MS. ZETTLER: From his file. 11 JUDGE POTTER: He's one of these people you 12 deposed? 13 MS. ZETTLER: Absolutely. It came from his 14 deposition. 15 JUDGE POTTER: What did he testify about in his 16 deposition? 17 MS. ZETTLER: He testified that he did an early 18 study of the clinical trial data base to look at the incident 19 of activation and sedation in the clinical trials and these 20 are the numbers that he found, 38 percent had been activated. 21 This is a report of his actual -- 22 JUDGE POTTER: And you've taken his deposition? 23 MS. ZETTLER: Absolutely. If you want, I'll 24 have Monica go get the deposition. This will come in in 25 Doctor Beasley's. 142 1 JUDGE POTTER: Okay. I'm going to overrule the 2 objection because I think although he's assuming something not 3 in evidence, he's assuming it's going to come in evidence and 4 he should ask this man if he degrees or disagrees, and then 5 Doctor Beasley at some point may say what it is. Objection is 6 overruled. 7 (BENCH DISCUSSION CONCLUDED) 8 Q. Were you aware, Doctor Thompson, that fluoxetine 9 is activating relative to tricyclics and tricyclics are 10 sedating relative to fluoxetine? 11 A. I will be happy to address that assertion, but I 12 cannot answer it yes or no without qualifying it in terms of 13 the disease and the doses that we're speaking about because 14 the answer's different. 15 Q. Did Doctor Beasley ever report it to you that 16 his analysis of the clinical trials indicating a difference 17 between fluoxetine and tricyclics as activating 19 percent in 18 fluoxetine and 4 percent in tricyclics? 19 A. I don't remember those numbers. And reading 20 this, I can't even tell which diseases and which trials are 21 being analyzed here, and I'm not sure how they were analyzed, 22 and I don't know the time periods and I don't know the doses. 23 This is not, you know, not a scientific publication, for sure. 24 Again, this is an issue I'm prepared to address 25 from the real data and I'll be glad to read this if you want, 143 1 but I will not agree with some of the assertions that you've 2 asked me about. 3 Q. So you can't agree or disagree based on any 4 report -- this is not in evidence, so you don't know at this 5 time how to respond to this? 6 A. No. Wait a second. I can respond definitively 7 to whether the drug is activating or sedating relative to 8 either placebo or tricyclics, but it requires an agreement as 9 to which diseases and doses we're talking about because the 10 answer's different. 11 Q. Well, maybe I'm confused. Let me ask you a 12 question about another document. Can you identify Exhibit 71, 13 Doctor Thompson? 14 A. Yes, sir. This is a report by Marlene Cohen 15 about -- I think this was when she was asked to review the 16 first fluoxetine safety update. 17 Q. And we talked about this exhibit in your 18 deposition in length, did we not? 19 A. Yes, sir. 20 MR. SMITH: We'd offer Exhibit 71, Your Honor. 21 MR. FREEMAN: No objection, Judge. 22 JUDGE POTTER: Be admitted. 23 SHERIFF CECIL: (Hands document to jurors). 24 Q. Now, as I understand it, Doctor Marlene L. 25 Cohen, Ph.D., is a scientist at Lilly? 144 1 A. Yes, sir. 2 Q. And I believe you described her in your 3 deposition as a very good scientist at Lilly? 4 A. Excellent. 5 Q. And one knowledgeable concerning serotonin? 6 A. Yes, sir. 7 Q. And she was asked in her job duties as a 8 scientist at Eli Lilly to review the fluoxetine safety update; 9 is that correct? 10 A. Yes, sir. 11 Q. And this was a safety update that was being sent 12 to the Food and Drug Administration? 13 A. I think this is the first one that we submitted. 14 Q. Okay. That would have been, then, in 1984 or 15 '85? 16 A. I thought the first safety update -- one of 17 those around that time period, I can't tell you for sure. 18 Q. The one of the NDA was submitted in September of 19 1983, and you do a safety update annually. 20 A. (Shakes head negatively). 21 Q. You don't do a safety update annually? 22 A. Well, no. There's an annual report to the IND. 23 It was right around this time that the FDA changed the NDA 24 regulations and created for the first time what they call the 25 safety update. There are actually three different times at 145 1 which you might be asked to submit it, but it's not annual. 2 And this I think was the first one we submitted, the huge 3 document that we submitted. 4 Q. And that would have been in '84 or '85, you 5 think? 6 A. I don't know the exact date. 7 Q. Would this have been the same safety update that 8 you purportedly included your response to the BGA to? 9 A. No. I purportedly included that in the IND 10 annual report, which was filed in '85, although it covered the 11 year of 1984, primarily. 12 Q. Okay. So we're talking about two different 13 things? 14 A. Yes, sir. 15 Q. All right. Turn with me to the second page of 16 the document, PZ 883 701, Point 8. 17 A. Yes, sir. 18 Q. Do you see that? 19 A. Yes, sir. 20 Q. It says here, "CNS Stimulation, Agitation and 21 Insomnia. From the data taken in concert, it might appear 22 that there is a somewhat greater incidence of CNS stimulation 23 with fluoxetine as compared to placebo." Correct? 24 A. Yes, sir. 25 Q. "For example, a greater incidence of insomnia 146 1 and anxiety was reported." And then she gives some volume and 2 page reference, does she not? 3 A. Yes, sir. 4 Q. In there she's pointing to specific places where 5 she sees that; right? 6 A. I think so. 7 Q. Is she pretty meticulous about her work? 8 A. Yes, sir. 9 Q. And she's not going to make a statement without 10 having there the exact reference to what she's speaking of? 11 A. She's an excellent scientist. 12 Q. All right. She goes on to say, "Agitation seems 13 pronounced," and gives a citation, does she not? 14 A. Yes, sir. 15 Q. "And a decrease in REM sleep was reported." 16 Correct? 17 A. Yes, sir. 18 Q. "And there may be a suggestion of manic 19 psychosis." Correct? 20 A. Yes, sir. 21 Q. "As with other antidepressant agents used in the 22 depressed population, mania" -- and what is that next word, is 23 that 'is' or 'and'? "Mania or CNS stimulation may be a minor 24 component to the actions of fluoxetine." Correct? 25 A. Yes, sir. That's what she says. 147 1 Q. I assume that her reference to page and volume 2 is references to page and volume of clinical trial data of the 3 human clinical trials done by Eli Lilly and Company. 4 A. I think that those are the actual volumes of the 5 safety update. I mean, I think that's Volume 9, Page 95 of 6 the safety update. 7 Q. And those pages and volumes have to do with the 8 Lilly human depressed clinical trials, do they not? 9 A. And other things, as well. But, I mean, I don't 10 think you could go to that page and find the case-report form 11 from the clinical trial. I think you can go to that page and 12 find an analysis about the clinical trials. 13 Q. I understand. Probably you're going to go to 14 that page and see some charts, graphs and things of that 15 nature that summarize a group of data; correct? 16 A. I think so. 17 Q. And it's -- the group of data that is being 18 summarized there is the Lilly depression clinical trial data; 19 correct? 20 A. I'm not sure it's limited to depression. 21 Q. Well, in '84, '85, were you studying Prozac for 22 any other uses other than depression? 23 A. Oh, yes, sir. 24 Q. Okay. Did you see this when it was done? 25 A. Probably. I certainly saw it during our 148 1 deposition together and I'm almost sure I would have seen it 2 at the time. But, you know, we ask so many scientists to 3 comment on reports like that that I can't remember the 4 specific comments from Doctor Cohen. 5 Q. Were you here when we introduced Plaintiffs' 6 Exhibit 36? 7 And may I show that to the Witness for 8 reference? 9 JUDGE POTTER: Sure. 10 Q. This was from Doctor Fuller's testimony where 11 rats -- 12 A Yes, sir; I saw that. 13 Q. -- on lower doses were eating well and gaining 14 weight, but there was a finding of a pronounced 15 hyperirritability in those rats was observed during the second 16 through the fourth weeks and has now disappeared from some of 17 the rats? 18 A. Yes, sir. 19 Q. Hyperirritability is a finding of activation and 20 stimulation, is it not? 21 A. Well, yes, it is, but one may not necessarily 22 conclude in a rat that it's due to any action of anything on 23 the brain. If you keep a rat from being able to urinate, for 24 example, they get very hyperirritable. 25 Q. All right. What about, then, let's talk about 149 1 some humans. Exhibit 38 in connection with Doctor Fuller's 2 deposition talks about a human. Says, "Some patients have 3 converted from severe depression to agitation within a few 4 days. In one case, the agitation was marked and the patient 5 had to be taken off drug. In future studies, the use of 6 benzodiazepines to control the agitation will be permitted." 7 Right? 8 A. Yes, sir. 9 Q. And that was July 1979, before your joining 10 Lilly? 11 A. Yes, sir. 12 Q. Would marked agitation be something that would 13 be considered activating? 14 A. Again, you have to put it in context of how it 15 was seen, Mr. Smith. I think that if by activating you mean a 16 drug acting directly on the brain and producing that 17 behavioral change, that's certainly one conclusion that you 18 could get to, but you could produce all kinds of agitation in 19 people if you just make them itch or feel uncomfortable, so 20 I'm just saying at 100 percent of the time you wouldn't get to 21 that conclusion. But we're looking at individual patients 22 from 1979 versus the massive data we have today? And before 23 you asked me is the drug activating or sedating; I'll say on 24 the basis of the data today, I'll answer that one 25 definitively. 150 1 Q. Well, tell me. 2 A. You want the answer? 3 Q. Definitively, activating or sedating? 4 A. Again, remember what I said, we have to talk 5 about which disease because the answer is different. So 6 should we use Mr. Wesbecker's disease and talk about 7 depression and not talk about obesity, obsessive-compulsive 8 disease and all the others? 9 Q. Is that what Joseph Wesbecker in your 10 understanding was suffering from on September 14th, 1989? 11 A. Yes, sir. 12 Q. Okay. 13 A. And we ought to also look at the dose that he 14 was taking, because the answer is different if you look at 80 15 milligrams versus 20 milligrams. So if we look at 20 16 milligrams of Prozac taken daily for four weeks and in a 17 person with depression, you want the answer as to whether it's 18 sedating or activating. The answer is -- and I'd like to show 19 you the numbers. 20 Q. Just tell us, sedating or activating? 21 A. You need to understand why I'm making the 22 assertion. With that restriction, depression like Mr. 23 Wesbecker had and the dose he took, the answer is it's 24 sedating and not activating. 25 Now, if you asked me what would be the answer in 151 1 depression at 60 milligrams compared to placebo, my answer 2 would be that it's both activating and sedating. 3 If you asked me at 60 milligrams in depression 4 to compare it with tricyclics, I would say it's less sedating 5 than tricyclics and its activation is not that far off from 6 tricyclics. 7 So, again, it depends upon -- that's why I was 8 saying it depends upon the disease and the dose what answer 9 you want, and I'd like to show the numbers so you understand 10 what I'm saying. 11 Q. Have you read Joseph Wesbecker's medical record? 12 A. No, sir; I have not. 13 Q. Do you know whether or not he was reporting that 14 he was sedated on September 11th, 1989, the last time he saw 15 Doctor Lee Coleman, M.D.? 16 A. No, sir. I don't know whether he used that word 17 or not. I think he said he was better. Didn't you bring that 18 out earlier in the trial? 19 Q. Well, we've got a copy of what Coleman reported. 20 It says, "Patient seems to have deteriorated. Tangential 21 thought. Weeping in session. Increased level of agitation 22 and anger. Question from Prozac. Patient states he now 23 remembers sexual abuse by co-workers and has called sex crimes 24 division of police. Because of deterioration, I encouraged 25 patient to go into the hospital for stabilization but he 152 1 refused. Plan: discontinue Prozac which may be cause. 2 Return to clinic two weeks." 3 Would an increased level of agitation and anger 4 normally to you as a medical doctor indicate, Doctor Thompson, 5 that a man is becoming sedated? 6 A. No, sir. 7 Q. Is it your testimony here that Prozac was 8 sedating to Joseph Wesbecker on September 11th, 1989? 9 A. Not to Mr. Wesbecker. But you asked me the 10 general question of is the drug activating or sedating, and I 11 answered that general question. 12 Q. That's your opinion? 13 A. Yes, sir. 14 Q. You were concerned about the dosage of Prozac 15 that Mr. Wesbecker was getting in looking at the issue as to 16 whether or not it was activating or sedating? 17 A. Well, I suggested -- I gave you the answer for 18 both the regular dose of 20 and a high dose of 60 because, 19 again, the answers are different depending on which dose you 20 look at. 21 Q. Does this product have a dose-related 22 side-effect profile? 23 A. Absolutely. 24 Q. When was that learned, that this product had a 25 dose-related side-effect profile? 153 1 A. Well, it depends on what you mean by learned. 2 All drugs that I've ever heard of have a dose-related 3 side-effect profile, but this one was really nailed down in 4 the fixed-dose studies, which Doctor Wernicke and Doctor Zerbe 5 and I did after the NDA had been submitted. 6 Q. What's the lowest efficacious dose of Prozac? 7 A. Probably 20 milligrams. 8 Q. All right. Can you identify Plaintiffs' 9 Exhibit 73, Doctor Thompson? 10 A. Yes, sir. It's an E-mail memo that -- I think 11 it's E-mail; it could have been just directly off the computer 12 rather than E-mail -- that I addressed to Dan Masica and 13 carbon copied to five other people June 13, 1988. 14 Q. You authored this, Doctor? 15 A. Yes, sir. 16 MR. SMITH: We'd offer Exhibit 73, Your Honor. 17 MR. FREEMAN: No objection, Judge. 18 JUDGE POTTER: Be admitted. 19 SHERIFF CECIL: (Hands document to jurors). 20 Q. You'd been on a trip; correct? 21 A. Yes, sir. 22 Q. And you attended the Psychiatrist Experience 23 Programs in Long Beach, California, on July 11th, 1988? 24 A. I may have made a mistake because the memo is 25 dated June 13 and I said the symposium was July 11, and I bet 154 1 you one of those months is wrong. 2 Q. Okay. This was the Psychiatrist Experience 3 Program; was that something that was put on by Lilly? 4 A. Yes, sir. 5 Q. Sponsored by Lilly? 6 A. Yes, sir. 7 Q. And were members of the Lilly psychiatric 8 advisory board there? 9 A. I think one was in the audience but that wasn't 10 the intent of the meeting. I think he was there just as a 11 speaker. 12 Q. Prozac was on the market at this time? 13 A. Yes, sir. 14 Q. In the United States? 15 A. Yes, sir. 16 Q. Hadn't been approved in Germany? 17 A. You said so. 18 Q. Well, it was approved in Germany in December 19 1989. 20 A. That was my point. 21 Q. So it hadn't been approved in June or July of 22 1988; correct? 23 A. If you're correct, that statement is correct. 24 Q. And it looks like you -- from reading over the 25 letter, you sat in the back of the room and made notes and 155 1 observed the procedure; is that right? 2 A. Yes, sir. And talked with a large number of the 3 psych -- many of the psychiatrists who were there. 4 Q. And you're not a psychiatrist, again? 5 A. No, sir. 6 Q. And you do not dispense on a regular basis 7 day-to-day psychotropic medications such as Prozac? 8 A. No, sir. 9 Q. And you didn't dispense Prozac or psychotropic 10 medications day to day for psychiatric disorders on a regular 11 basis when you did practice medicine? 12 A. It wasn't on the market, sir. I mean, I'm still 13 licensed to practice medicine. 14 Q. I said and other antidepressants, I thought. 15 A. Oh, I'm sorry. I did -- that statement wouldn't 16 be totally true. I didn't do a lot of it. 17 Q. All right. Page 2 -- I mean, Paragraph 2 of 18 Page 1 you say, "There is tremendous pressure from gurus and 19 practicing psychiatrists to make ten milligrams or even five 20 milligrams available. They are wrong that 20 milligrams is 21 excessive from the safety data we have, but they will not lose 22 appreciable efficacy at 10 milligrams; correct? 23 A. I think -- it's not Page 2 on my copy, but you 24 certainly read it correctly. 25 Q. I'm sorry. I meant Paragraph 2 of Page 1; 156 1 correct? 2 A. Yes, sir. 3 Q. Now, were the gurus there the people who were 4 supposedly opinion leaders and eminent psychiatrists? 5 A. Yes, sir. 6 Q. Is that why you referred to them as gurus, or 7 gurus? 8 A. Yes, sir. 9 Q. Was one of those gurus on Lilly's psychiatric 10 advisory board at that time? 11 A. I think Doctor Dunner, who is mentioned later, 12 was at one time or another on the advisory board. That's why 13 I mentioned him. 14 Q. Now, 10 milligrams wasn't available in pulvule 15 dosage, was it? 16 A. Not at that time. 17 Q. And didn't -- it wasn't available -- 10 18 milligrams wasn't available on September 11th of 1989, either, 19 was it? 20 A. I don't know when we marketed the liquid form; I 21 don't know that in the United States or the other countries. 22 Q. I'm talking about the pulvule. 23 A. I don't think the pulvule was marketed in the 24 U. S. at that time. 25 Q. In fact, the pulvule, 10-milligram pulvule 157 1 wasn't marketed until February of 1994, this year; correct? 2 A. If you say so. I don't know. 3 Q. You say there's tremendous pressure to make 4 10 milligrams or even 5 milligrams available; correct? 5 A. Yes, sir. 6 Q. Five milligrams in the pulvule form has never 7 been available, has it? 8 A. Only as a clinical trial, too. 9 Q. We'll talk about that in a minute. But the 10 psychiatrists and gurus -- practicing psychiatrists and gurus 11 were wanting less dosage of Prozac, weren't they? 12 A. Some were wanting more, except it's a lot easier 13 to get to more than it is to less. 14 Q. Well, you say they want -- "There's tremendous 15 pressure from the gurus and practicing psychiatrists to make 16 10 milligrams or even 5 milligrams available." 17 A. But, in all fairness, they also were pushing the 18 dose higher than I thought they ought to go. It's easy to 19 give two or three pills a day; it's not easy to take a little 20 capsule apart and figure out how to get half out of that. 21 Q. Well, it doesn't sound like that's what they're 22 trying to do, give two or three pills a day, Doctor. You go 23 on to say, "As they will titrate and are between 5, 10, to 40 24 milligrams daily, no matter what we do we should make it 25 easier for them. I agree with the proposal to make available 158 1 a 10-milligram dose without changing the labeled-dose 2 guidelines as soon as possible." Correct? 3 A. Yes, sir. 4 Q. In other words, it was -- some of the 5 psychiatrists in actual practice with Prozac were dividing 6 these pulvules up, weren't they, Doctor? 7 A. Yes, sir. 8 Q. And they would in fact and indeed in some 9 patients tell those patients to empty a 20-milligram pulvule 10 into some liquid, be it orange juice, water or whatever. 11 A. They usually were recommending juice, I think. 12 Q. Beg your pardon? 13 A. I think they were usually recommending fruit 14 juice. 15 Q. Some type of fruit juice. And to have them stir 16 it up and then divide that into four separate glasses; right? 17 A. That's what they were telling me. 18 Q. And they were having the patient drink one of 19 those glasses; right? 20 A. Some of them were using one, which would be, as 21 you described it, 5 milligrams; some of them were using two. 22 Q. All right. But they were getting less dosage 23 per day; right? 24 A. Well, so far we haven't talked about dose per 25 day. I think you're correct, but some of them were just using 159 1 divided doses because they wanted to give them a dose in the 2 morning and a dose in the afternoon, which they also didn't 3 need to do. 4 Q. But the practice was is they were trying to 5 reduce the dosage to reduce the side effects, weren't they? 6 A. No, sir. No. Now you've gone too far. 7 Q. Well, you say, "They are wrong that 20 8 milligrams is excessive from the safety data we have here." 9 A. That's exactly correct. 10 Q. So I assume they were trying to reduce the 11 dosage because the perception they had that 20 milligrams was 12 excessive from a safety standpoint. It's what's written here. 13 A. I've got to explain this because you're going 14 farther than I wrote or meant. American psychiatrists, in 15 fact, psychiatrists around the world at this time had never 16 had a drug that they didn't have to titrate. In fact, one of 17 the biggest problems with tricyclics, as you know, is that you 18 have to constantly adjust the dose of the drug for the 19 patient; you have to measure blood levels of the drug to get 20 it right. This was the first time that anybody had ever done 21 studies of fixed dose. And that's what I reference right 22 here, the 0, 20, 40, 60. We talked about it before, some 23 patients getting only 20, some people getting only 40 24 milligrams a day, some getting 60, some getting zero, a 25 placebo or sugar pill. No one had ever done studies like that 160 1 before. 2 And we were astounded, I can tell you. We were 3 astounded that 20 milligrams worked as well as or better than 4 any of the other doses. So we really had a problem because 5 all the psychiatrists their whole career had been used to 6 constantly titrating doses up and down to get it right, and 7 here we were sitting on a drug where literally every patient 8 would do well on one dose. We couldn't convince them of that. 9 Q. Are you saying that every patient would do well 10 on one dose? 11 A. That's exactly my assertion. From the data we 12 have from these three studies, we could not find -- let's put 13 it this way, we could not find any patients who needed either 14 a smaller or larger dose for treating depression -- this is 15 only for depression -- than 20 milligrams a day, and it 16 certainly didn't need to be given but once a day. 17 Q. Is it your testimony here -- and I understand 18 you're not a psychiatrist, Doctor Thompson. But from your 19 perspective as the chief scientific officer of Eli Lilly and 20 Company, is it your testimony that 20 milligrams is never an 21 excessive dose of Prozac in depressed individuals? 22 A. Certainly in any ordinary depressed individual. 23 Now, if you got into very small children or very, very frail 24 elderly, I don't have enough data to be able to assert that. 25 But in ordinary adults of ordinary size and shape, 161 1 20 milligrams is the only dose that's needed for depression. 2 Q. And it won't be excessive is what you're saying? 3 A. No, sir. It will not be excessive. 4 Q. But the psychiatrists in this Summer 1988 5 meeting felt that it was, didn't they? 6 A. No, sir. I'm not saying here that they felt it 7 was excessive. They were doing all kinds of dose titration up 8 and down from 20 milligrams. 9 Q. But you're saying here, "They are wrong that 20 10 milligrams is excessive from the safety data we have." 11 Apparently they were telling you 20 milligrams was excessive; 12 otherwise, why would you have mentioned it here? 13 A. Mr. Smith, in all fairness, if you read the next 14 paragraph, it says, "I heard that general practitioners were 15 using 80 milligrams, and the psychiatrists and I were 16 concerned with doses this great." So it was in both 17 directions up and down. I mean, we were very frustrated. I 18 was very frustrated. We had done these incredibly beautiful 19 studies and everybody who was an expert had praised them and 20 it said use 20 milligrams, and we couldn't convince all the 21 psychiatrists to do that. 22 Q. So you agreed with the proposal to make 23 available a 10-milligram dose? 24 A. I thought dissolving the drug in orange juice or 25 cutting the tablets in half or the capsules in half was crazy. 162 1 So if they were going to do that, we ought to make it more 2 scientifically available. Absolutely. You notice I said in 3 there that it wouldn't change the dosage guidelines. So the 4 label would still say the dose of this drug is 20 to 80 5 milligrams a day. But here, we'll give you a 10-milligram 6 capsule; if you want to give one of those in the morning and 7 one at night or you want to give two in the morning, the 8 patient can't swallow a big capsule, it doesn't mean we mind 9 doing it. 10 Q. All your data, beautiful data suggested 20 11 milligrams was great and yet you were going to make available 12 a 10-milligram dose? 13 A. Without changing the recommended daily dose of 14 20 to 80 milligrams a day, Mr. Smith. 15 Q. Can you identify Exhibit 74, Doctor Thompson? 16 A. Yes, sir. The first two pages look to be a memo 17 from Patrick Keohane to me and other people, dated 18 21 March 1991, and the third page seems to be a memo from 19 Walter Lange, or Wally Lange, to Mr. Mayr and Voris, carbon 20 copied to me on April 2nd, 1991. 21 MR. SMITH: We'd offer Exhibit 74, Your Honor. 22 JUDGE POTTER: Be Admitted. 23 MR. FREEMAN: No objection. 24 SHERIFF CECIL: (Hands exhibit to jurors). 25 Q. Exhibit 74 is a document authored by your 163 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 163 1 medical director in UK in Ireland, Patrick Keohane? 2 A. Keohane. Yes, sir. 3 Q. Keohane. And it's directed to you and Doctor 4 Zerbe? 5 A. And Doctor Weinstein and Mr. Voris. 6 Q. All right. And it has to do with Prozac 7 10 Milligrams Solid Formulation Position? 8 A. Yes, sir. 9 Q. And it says, "Views have been expressed on the 10 need for availability of a solid form of Prozac below 20 11 milligrams. They come from two main sources." Correct? 12 A. Yes, sir. 13 Q. One lists regulatory? 14 A. Yes, sir. 15 Q. And it mentions the medicine -- it says, "We 16 worked closely with the Medicines Control Agency." What is 17 that, sir, do you know? 18 A. That's the regulatory authority in the United 19 Kingdom, not Ireland. Remember we talked about the Committee 20 on the Safety of Medicines being an advisory group of 21 academicians to the regulatory authority? This was the 22 regulatory authority. 23 Q. So MCA is like the FDA and like the BGA? 24 A. Well, except the FDA has 30 or 40 times more 25 people and operates differently, but they're the regulatory 164 1 authority in the country for drugs. 2 Q. That's simply what I was asking you, Doctor 3 Thompson. 4 A. Mr. Smith, when you ask me if they're similar, 5 they're similar in some ways and they're different in others. 6 Q. All three entities are charged with the 7 governmental responsibility for ensuring safety and efficacy 8 of drugs marketed in their country? 9 A. Yes, sir. 10 Q. This regulatory believes -- down here in the 11 second paragraph say they believe that 10 milligrams is 12 necessary or lower dosage is necessary for the following 13 reasons: "A, Alternate-day dosing recommended in some 14 patients may reduce compliance." Correct? 15 A. Yes, sir. 16 Q. And what they're talking about there is when a 17 doctor wants a patient to take -- get a lower amount of a 18 medicine and he may tell the patient, take the medicine 19 Monday, Wednesday, Friday, or every other day; correct? 20 A. Yes, sir. 21 Q. And the problem with that is patients forget 22 whether they took it the morning before or not; right? 23 A. Yes, sir. 24 Q. It's easier to get patient compliance if you say 25 take a pill every morning; right? 165 1 A. I think so. 2 Q. Well, do you know that? 3 A. Actually, that study hasn't been done. It's a 4 very interesting one that we've been quite interested in. 5 There's not a definitive study on that, but I agree with you 6 that that's the most likely thing. 7 Q. All right. And what the CSM was saying is 8 reduce the doses, don't have a higher dosage and prescribe it 9 every other day, because your patients may forget, you're got 10 going to get good patient compliance; right? 11 A. Yes, sir. 12 Q. Point B there says, "Five-milligram data 13 interpreted as showing efficacy," doesn't it? 14 A. Yes, sir. 15 Q. Now, to be honest -- to be clear here, 16 5 milligrams of Prozac is 25 percent as powerful as 17 20 milligrams; is that right? 18 A. Oh, I wish you hadn't said it quite that way. 19 It's 25 percent as much drug. 20 Q. All right. 21 A. But remember before you showed me a document 22 that talked about nonlinear kinetics? Don't make me say it's 23 25-percent less powerful, okay? It's 25-percent less drug. 24 Q. All right. And the CSM interpretation was that 25 the 5-milligram data was efficacious. 166 1 A. That's what it says. It doesn't say CSM. It 2 says, "The regulatory authorities believe," but that's the way 3 I'd interpret it. 4 Q. It would be the MCA, really? 5 A. I think that's correct it. 6 Q. And, again, the 5-milligram data that they're 7 looking at is your 5-milligram data that you submitted to 8 England for approval in the UK? 9 A. I presume it went to them, but the publication 10 speaks for itself. It's an excellent study. 11 Q. Point C says, "Relatively large number of 12 Lilly-supplied events and UK yellow-card reports may be 13 reduced if 10-milligram dose used in some patients." Correct? 14 A. Yes, sir. 15 Q. Now, that yellow card is what you were referring 16 to earlier, that when a physician in England has an adverse 17 event he does what's called a yellow card? 18 A. That's one way of reporting it. The others, of 19 course, came from Lilly from events all over the world. So 20 what they mean here is the regulators think the number of 21 adverse events would be reduced if you went to a lower dose. 22 Q. Reasonable? 23 A. It sure sounds good, but it turns out the data 24 doesn't substantiate that. But it really does sound good. 25 Q. Point D is, "Committee on Safety of Medicines 167 1 appears to have a position that 10-milligram dose would be 2 effective." 3 A. Yes, sir. 4 Q. That's from reviewing your data, also, isn't it? 5 A. Well, I don't know where they got the position 6 because, to my knowledge, we've never done a depression study 7 using a dose of 10 milligrams a day. In obesity, 8 10 milligrams is only slightly better than 0 milligrams, so we 9 do have data on a 10-milligrams-a-day dose, but to my 10 knowledge even as of today, I don't think we have a study in 11 depression looking at 10 milligrams a day. 12 Q. Do you know why you don't have a 10-milligram 13 study in depression? 14 A. Yes, sir. It's because 20 milligrams has an 15 almost impossible-to-distinguish-from-placebo side-effect 16 profile and it has all the efficacy of higher doses, including 17 60 milligrams, and in some cases it actually looks either the 18 same or better than 5 milligrams. So there wasn't any reason 19 -- and I will assert that as of today, there isn't any reason 20 to go to a dose lower than 20 milligrams unless you're talking 21 about extremely unusual patients. 22 Q. Point E here says that, "They -- being the 23 CSM -- forced the dose of Sertraline and Paroxatine down based 24 on Prozac perception in UK." 25 A. Yes, sir. 168 1 Q. Now, what are Sertraline and Paroxatine? 2 A. They are two other selective serotonin uptake 3 antagonists which are similar to Prozac. And to understand 4 that, you need to understand Doctor Temple's, at the FDA, 5 strong feeling that many drugs -- 6 Q. Just a second, Doctor. I didn't ask you 7 anything about Doctor Temple's strong feelings, did I? 8 MR. FREEMAN: Let him finish his answer, Judge. 9 JUDGE POTTER: I tell you what, Mr. Smith, 10 because with the buzzing and whatnot, I'm not really sure 11 where we are. 12 Q. Point E here says, "They forced the dose of 13 Sertraline and Paroxatine down based on Prozac's perception in 14 UK," "they" meaning the CSM; right? 15 A. Yes, sir. It's either the CSM or the MCA. 16 Q. And Sertraline and Paroxatine are cousin SSRIs 17 of Prozac? 18 A. Yes, sir. 19 Q. Manufactured by competitors? 20 A. Yes, sir. 21 Q. Then, apparently, the psychiatrists on Page 2 of 22 the document indicate in the second paragraph -- third 23 paragraph, most -- they say most psychiatrists accept the 24 20-milligram dose is appropriate most times in most patients, 25 but want lower-dose flexibility; correct? 169 1 A. Yes, sir. 2 Q. Is Prozac 10 milligrams available in the United 3 Kingdom? 4 A. I think the liquid form is on the market so you 5 could give any dose you want to, but I'm not 100-percent sure 6 of that. 7 Q. How about pulvule, solid formulation? 8 A. I don't know. 9 Q. Can you identify Exhibit 75, Doctor Thompson? 10 A. Yes, sir. This is an E-mail memo from John 11 Heiligenstein, who we've talked about is a psychiatrist at 12 Lilly, to me, Doctor Allan Weinstein, Doctor Bob Zerbe and 13 himself and two other psychiatrists. 14 MR. SMITH: We'd offer Plaintiffs' Exhibit 75, 15 Your Honor. 16 MR. FREEMAN: No objection. 17 JUDGE POTTER: Be admitted. 18 SHERIFF CECIL: (Hands document to jurors). 19 Q. You took a trip to Long Beach, but Doctor 20 Heiligenstein got a trip to Vienna? 21 A. He had done all the hard work. 22 Q. All right. Doctor Heiligenstein is a 23 psychiatrist at Lilly, is he not? 24 A. Yes, sir. He's a child psychiatrist. 25 Q. He is more familiar with depression and more 170 1 familiar with antidepressant treatment than you, sir? 2 A. If you say so. 3 Q. Well, he is by training, isn't he? 4 A. Yes, sir. I'm not a psychiatrist. 5 Q. He reports on the Vienna meeting. He said, "I'd 6 like to share the sense of what I heard. One: Clearly, very 7 clearly, there is a need for a lower dose in pulvule form. 8 Five milligrams would be most appropriate, although at the 9 child psychiatry meetings in Chicago, 2.5 milligrams was 10 suggested. The liquid formulation will only partially address 11 this need." Correct? 12 A. Yes, sir. 13 Q. "Two: We have not established the lowest 14 effective dose, and if we listen to the prescribers, some 15 effort should be made to do this; if not, M.D.s will continue 16 to dissolve pulvules and will anxiously await new medications 17 with greater flexibility in dosing." Correct? 18 A. Yes, sir. 19 Q. Do you disagree with Doctor Heiligenstein when 20 he says, "We have not established the lowest effective dose"? 21 A. Yes, sir. 22 Q. You just disagree with him? 23 A. I think it's a matter of scientific debate, but 24 my feeling is that 20 milligrams is, although 10 milligrams 25 might be the lowest effective dose, we just don't have any 171 1 data on 10 milligrams. 2 Q. Can you identify Exhibit 79, Doctor Thompson? 3 A. Yes, sir. This is an E-mail memo from me to 4 Charles B. Sampson; Doctor Sampson was Director of Statistical 5 and Mathematical Sciences at Lilly at that time, carbon copied 6 to Doctor Bob Zerbe and myself, June 11, 1991. 7 MR. SMITH: Offer Plaintiffs' Exhibit 79, Your 8 Honor. 9 MR. FREEMAN: No objection. 10 JUDGE POTTER: Be admitted. 11 SHERIFF CECIL: (Hands document to jurors). 12 Q. Doctor Thompson, since this exhibit is in real 13 small print, I got a blowup for us to help us read it. 14 Is it all right if I hold it this way, Your 15 Honor? 16 JUDGE POTTER: Fine. 17 Q. It says, "Charlie, let me ask you for your help 18 in putting together two slides for the board. I've got to say 19 something about 10 milligrams both in regard to attributes and 20 to the logistics of when we will file in the U. S. 21 International filing is a big, big problem." Charlie is the 22 statistician; right? 23 A. Yes, sir. 24 Q. And you're going to make a presentation to the 25 board of directors at Eli Lilly and Company concerning a 172 1 10-milligram dose? 2 A. Yes, sir. 3 Q. Form? Is it called dosage form? 4 A. Yes, sir. 5 Q. All right. And you say international filing is 6 a big, big problem. What was the big, big problem in 7 international filing? 8 A. Well, each country has its own sets of rules 9 about what you need to add a new dosage form, and some of them 10 will not allow you to use the same inactive ingredients that 11 you can use in the United States or another country. So, 12 often, to put a new dosage form on the market, you have to 13 test a whole variety of different formulations, one for 14 France, one for Germany. Each one of those is very expensive. 15 They require a chemical analysis, and you have to measure the 16 pill and put it on stability testing, and you put it on high 17 temperature and high humidity and you measure the drug and 18 break down products and it's a very complicated and expensive 19 procedure to do it, and it takes a long time. 20 Q. But you're making a presentation to the Lilly 21 board of directors about whether to make a 10-milligram dosage 22 form; is that right? 23 A. I think my charge was to come there and talk 24 about 10 milligrams, what we knew about it, et cetera. I 25 wasn't going to make a proposal to either do it or not do it. 173 1 Q. All right. It says, "I don't think we have any 2 10-milligram efficacy data. We have the Wernicke study of 3 5 milligrams versus 20 and 40." It says, "Some people have 4 massaged those data to make 5 milligrams look not quite as 5 good as 20 milligrams." 6 A. Yes, sir. 7 Q. "I'm not sure I know how that massage was done, 8 but I'd probably need a slide to know whatever it is that 9 makes it look less good. I'd probably also like a slide that 10 shows a more global view of how it works. Do we have a 11 display by week of the HAM-D total changes?" 12 A. Yes, sir. 13 Q. "As I recall, 5 milligrams actually went down a 14 little faster than the others and ended up about the same. 15 Help me if you will on what to show on 10 milligrams to the 16 board." Correct? 17 A. Yes, sir. 18 Q. Okay. When you say HAM-D went down faster and 19 up to about the same, you're talking about the HAM-D 20 depression scores? 21 A. Yes, sir. 22 Q. Total HAM-D depression scores, are you not? 23 A. Yes, sir. 24 Q. And you're saying that actually on 5 milligrams 25 the people -- people's HAM-D indicating less depression, went 174 1 down faster on 5 milligrams; right? 2 A. Yes, sir. When I was massaging the data, that's 3 the result that I got looking at the composite 21-question 4 HAM-D scores. But early on, of course, you can't distinguish 5 an active antidepressant from placebo, so whatever happened in 6 Week One or Two, you wouldn't expect to be seeing a drug 7 effect until you got out to Week Three. This was a point of 8 great controversy. Some of us felt that 5 milligrams might 9 work in patients; other people felt that you ran the risk of 10 leaving some patient with a life-threatening illness 11 untreated, and the problem is that if you applied 10 or 15 12 different statistical tests you'd get 10 or 15 different 13 answers. 14 Q. Well, you say here this massaging the data, too, 15 was to make 5 milligrams -- you say five people have massaged 16 this data to make 5 milligrams look not quite as good as 20. 17 A. You do some of the statistical tests you come 18 out with one answer, when you do others you come out with 19 another. So since Doctor Sampson was not involved in the 20 debate and I regarded him as being the best we had, I was 21 going to Charlie and saying, "Look, you look at all of them, 22 you massage the data and you tell me what to say." 23 Q. But the data had already been massaged to make 24 5 milligrams look not as good as 20 milligrams, hadn't it? 25 A. Well, when I did it, I could get some tests to 175 1 say 5 looked worse, some to say it looked the same, some 2 better, depending on what week you looked at it. Other people 3 were using more sophisticated statistical tests than I was 4 using. This was a huge debate. 5 Q. Well, is it the practice of Eli Lilly and 6 Company to massage data? 7 A. Goodness gracious, I hope so. We even have a 8 super computer so we can massage and look at it from every 9 possible perspective, does it make a difference if the patient 10 has a different age, obesity, gender, whatever. 11 Q. Doctor Wernicke did the study you're talking 12 about, didn't he? 13 A. Actually, Doctor Wernicke, Doctor Zerbe and I 14 designed it. Doctor Wernicke was the monitor for that study. 15 Q. Did you know that he's testified under oath in 16 depositions taken in this case that he thinks you massage 17 people, not data? 18 A. As you pointed out -- 19 MR. FREEMAN: He's mischaracterizing again 20 testimony. 21 JUDGE POTTER: Let me see you-all up here again. 22 (BENCH DISCUSSION) 23 MR. FREEMAN: He's now characterizing testimony 24 that has not even been heard. 25 JUDGE POTTER: But is it accurate? 176 1 MS. ZETTLER: It's absolutely accurate when we 2 asked him what it meant to massage data, he looked at us 3 incredulously and he said, "You massage people, not data." 4 JUDGE POTTER: Let's see it then. 5 MS. ZETTLER: I could have Monica go get it; it 6 will take her two minutes. It will be two minutes. It will 7 come in on his video, the incredulous look and everything. 8 JUDGE POTTER: Overrule the objection. Ask your 9 question, Mr. Smith. 10 (BENCH DISCUSSION CONCLUDED) 11 Q. The question was, Doctor Thompson, were you 12 aware that Doctor Wernicke has testified in this case that you 13 massage -- testified in depositions taken in this case that 14 you massage people, not data? 15 A. I'm not aware of that, but I don't massage 16 anybody, but I do massage an awful lot of data. That's my 17 hobby. 18 Q. Did I give you Exhibit 78? 19 A. Yes, sir. 20 Q. Can you identify it? 21 A. Yes, sir. It appears to be a memo. Again, this 22 is not E-mail, this is a memo from Melissa Humbert to Tom 23 Jeatran with a carbon copy to Earlene Ashbrook, Mr. Hofmann, 24 Doctor Max Talbott and Doctor Wernicke. 25 MR. SMITH: We offer Exhibit 78, Your Honor. 177 1 MR. FREEMAN: No objection. 2 JUDGE POTTER: Be admitted. The date is June 5, 3 1985. 4 SHERIFF CECIL: (Hands document to jurors). 5 Q. All right. The subject to this Exhibit 78 is a 6 Fluoxetine Fixed Low-Dose Protocol: CT Materials. I assume 7 that's clinical trial materials; is that right? 8 A. Yes, sir. 9 Q. Is this the Wernicke study? 10 A. There were three Wernicke studies often called 11 that. This was the second one, which compared 0, 5, 20 and 40 12 milligrams as fixed dose in patients with depression. 13 Q. The memo says, "A decision has been made by Mr. 14 Wood to amend the fluoxetine fixed low-dose protocol. Upon 15 his recommendations, we will exclude the 10-milligram 16 fluoxetine dosage regimen." Correct? 17 A. Yes, sir. 18 Q. Tell the jury who Mr. Wood is. 19 A. Mr. Richard Wood at that time was chairman and 20 chief executive officer of Eli Lilly and Company, a position 21 he had held for 17, 18 years at this time. 22 Q. Tell the jury what -- where he got his M.D. 23 Degree. 24 A. He has an M.B.A. from Wharton; he doesn't have 25 an M.D., sir. 178 1 Q. Okay. And how many clinical trials did your 2 Master of Business Administration, chairman of the board 3 change the protocols on? 4 MR. FREEMAN: That's argumentative in nature, 5 Your Honor. 6 JUDGE POTTER: Overruled. He can answer it. 7 A. I'll be happy to explain the meeting that led to 8 this decision, sir. 9 Q. No. My question was how many protocols did the 10 chairman of the board who had the M.B.A., Master of Business 11 Administration, change? How many protocols? 12 A. A couple in the time that I've been at Lilly. 13 Q. "A decision was made by Mr. Wood to amend the 14 fluoxetine fixed low-dose protocol. Upon his recommendation, 15 we will exclude the 10-milligram fluoxetine dosage regimen." 16 Correct? 17 A. Yes, sir. 18 Q. It says, "This procedure has been discussed with 19 Max Talbott for regulatory adherence." 20 A. Yes, sir. 21 Q. The entire clinical trial assembly had to be 22 revised and you had to remove, physically, patient kits that 23 contained 10 milligrams; correct? 24 A. Yes, sir. 25 Q. This is June 1985; right? 179 1 A. Yes, sir. 2 Q. Ten milligrams didn't get studied in this trial, 3 did it? 4 A. Did not get studied in that trial. 5 Q. Ten milligrams hadn't been studied before this 6 trial, had it? 7 A. I don't know whether the obesity trial was 8 before this trial or after. 9 Q. Ten milligrams for depression hadn't been 10 studied before this trial, had it? 11 A. No, sir. 12 Q. And 10 milligrams for depression hadn't been 13 studied on September 14th, 1989, either, had it? 14 A. No, sir. I don't think it's been studied as of 15 today. 16 Q. Can you identify Exhibit 76? 17 A. Yes, sir. I think this is an E-mail -- 18 MR. FREEMAN: Your Honor, we have an objection 19 to this exhibit. He could not identify it in his deposition. 20 JUDGE POTTER: Okay. Let me see you-all. 21 (BENCH DISCUSSION) 22 JUDGE POTTER: Mr. Freeman? 23 MR. FREEMAN: Your Honor, we object to this 24 Exhibit No. 76 upon the grounds that this Witness has no 25 knowledge of it. He could not identify it in his deposition; 180 1 he can't identify it now, and to talk about the content is not 2 the way to go about introducing the document. 3 MS. ZETTLER: This is not the deposition exhibit 4 for Doctor Thompson. 5 MR. FREEMAN: Yes, it was. Absolutely. 6 JUDGE POTTER: Show it to him and ask him if he 7 knows what it is. If he says no, then leave it at that. 8 (BENCH DISCUSSION CONCLUDED) 9 Q. Can you identify Exhibit 76? 10 A. Yes, sir. I believe it to be an E-mail memo 11 from Lorenzo Tallarigo -- I think the "T" is cut off there -- 12 to Allan Weber with copies to Sigrid Heymanns, William 13 Oldfield, Francoise Rossignol, Max Talbott, Tallarigo back to 14 himself, and Steve Whittaker, dated December 17, 1990. 15 Q. And this is a Lilly E-mail document? 16 A. Yes, sir. 17 MR. SMITH: And we'd offer 76, Your Honor. 18 MR. FREEMAN: No objection. 19 JUDGE POTTER: Be admitted. 20 SHERIFF CECIL: (Hands document to jurors). 21 Q. This exhibit is dated December 17th, 1990, is it 22 not? 23 A. Yes, sir. 24 Q. Five years after Mr. Wood had decided to kill 25 the 10-milligram clinical trials; right? 181 1 A. Four and a half. 2 Q. Paragraph One says, "We need to produce 3 evidence, clinical trials, for the benefit of these new 4 dosages." And the new dosages under consideration was 10 5 milligrams, wasn't it? 6 A. I don't know. 7 Q. Well, it says -- in the last P.S. there, it 8 says, "As you may imagine, our price will be half of the 9 actual for the 10 milligram and one-fourth for the 5 10 milligrams. What our objective is." Right? 11 A. That's what it says. 12 Q. So, 20 milligrams was what was available; 13 correct? 14 A. Again, I don't know what was available in Italy 15 in 1990, sir. I'm sorry. I don't know whether they had the 16 liquid available or not. 17 Q. Well, in the pulvule form you know it was just 18 20 milligrams, don't you? 19 A. I think that's correct. 20 Q. It says, "We need to produce evidence, clinical 21 trials, for the benefit of these new dosages," which would 22 have been 10 or 5; right? 23 A. I think that's reasonable from this memo, but I 24 wasn't part of this conversation. 25 Q. "We should be very careful not to suggest that 182 1 these are more appropriate -- are the more appropriate dosages 2 if we do not want to run the risk to have the higher dosages 3 withdrawn from the market." 4 A. That's what Doctor Tallarigo said. 5 Q. It says, Number Two, "It's difficult to answer 6 if we do not know which data we're talking about." Right? 7 A. Yes, sir. 8 Q. It says, "It depends which evidence we have of 9 the benefits." Right? 10 A. Yes, sir. 11 Q. Then he says, "P.S. As you may imagine, our 12 price will be half of the actual for the 10 milligrams and 13 one-fourth for the 5 milligrams. What our objective is, 14 question mark." Correct? 15 A. That's what he said, sir. 16 Q. When he says "our price," he's talking about the 17 price that Lilly would be able to charge the patient for the 18 medication, isn't he? 19 A. Well, in Italy it's a strange system. I think 20 it's a government reimbursement price. I wasn't aware that 21 the Italians worked this way. 22 Q. It would be the price that Lilly got for the 23 sale of the medication, regardless of who paid for it? 24 A. I think that's right. 25 Q. And if it was 10 milligrams, it would be half? 183 1 You'd get half of what you normally get for 20 milligrams? 2 A. I wasn't aware that that was true, but if that's 3 the way it is in Italy, then that's what it says. 4 Q. What it says, isn't it? 5 A. Yes, sir. 6 Q. And one-fourth for the 5 milligrams? 7 A. Yes, sir. 8 Q. You're going to have a reduced price profit if 9 you sell the product in a lower dosage, correct, according to 10 this exhibit? 11 A. The price will be less, yes. 12 Q. All right. And if you lower the dosage, you run 13 the risk to have higher dosages withdrawn from the market, 14 correct, Doctor Thompson? 15 A. That's what he said. 16 MR. SMITH: Your Honor, I think this is all I 17 have in that -- on that subject at this time. 18 JUDGE POTTER: Maybe this is a good time to take 19 the evening recess. 20 Ladies and gentlemen, I'm going to give you the 21 same admonition I've given you numerous times, and I emphasize 22 again the portion about letting anybody communicate with you 23 on this case applies to friends, curious, uninterested people, 24 I mean, unconnected with this case but people who are 25 interested in what you've been doing. It also applies to the 184 1 news media. Don't discuss it among yourselves and do not form 2 or express opinions about it until it is finally submitted to 3 you. 4 We'll stand in recess until 9:00 tomorrow 5 morning. For your-all's information, tomorrow will be kind of 6 a half day. Stand in recess till 9:00 tomorrow morning. 7 (PROCEEDINGS TERMINATED THIS DAY AT 5:05 P.M.) 8 * * * 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 185 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 186 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