1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT DIVISION ONE (1) 2 3 JOYCE FENTRESS, ET AL. PLAINTIFFS 4 5 VS. DEPOSITION FOR PLAINTIFFS 6 7 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 8 * * * * * * * * * * 9 10 DEPONENT: DR. HANS WEBER 11 DATE: SEPTEMBER 10, 1994 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 20 (502) 589-2273 Page 1 1 * * * * * * * * * * 2 3 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 4 INDIANAPOLIS DIVISION 5 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 6 Litigation ) 7 * * * * * * * * * * 8 NO. 91-02496-A 9 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 10 V. ) DALLAS COUNTY, TEXAS ) 11 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 12 * * * * * * * * * * 13 NO. 92-14775-E 14 RICHARD HAROLD CROSSETT, JR., ) IN THE 15 CHAD H. CROSSETT, AMY MICHELLE ) DISTRICT CROSSETT AND KRISTEN ANN CROSSETT, ) COURT OF 16 INDIVIDUALLY AND AS SURVIVORS OF ) AND ON BEHALF OF THE ESTATE OF ) 17 JOCQUETTA ANN CROSSETT, DECEASED ) ) 18 V. ) DALLAS COUNTY, ) TEXAS 19 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, TEXAS ) 20 PSYCHIATRIC COMPANY, INC. ) D/B/A/ HCA WILLOW PARK ) 101ST JUDICIAL 21 HOSPITAL, JAMES K. WITSCHY, M.D., ) DISTRICT AND DOUG BELLAMY, ED.D. ) Page 2 1 * * * * * * * * * * 2 NO. A-921,405-C 3 MARIA GUADALUPE REVES ) IN THE 4 INDIVIDUALLY AND AS NEXT ) DISTRICT COURT FRIEND OF GRANT JULIAN REVES ) OF 5 A MINOR CHILD, AND ON BEHALF ) OF THE ESTATE OF CHRISTIAN ) 6 MARIE REVES, DECEASED ) ) ORANGE COUNTY, 7 V. ) TEXAS ) 8 ELI LILLY & COMPANY, DISTA ) PRODUCTS COMPANY, RAVIKUMAR ) 9 KANNEGANTI, M.D., HOSPITAL ) CORPORATION OF AMERICA, A ) 10 TENNESSEE CORPORATION, HEALTH ) SERVICES ACQUISITION CORP., ) 11 A DELAWARE CORPORATION, ) HCA PSYCHIATRIC COMPANY, A ) 12 DELAWARE CORPORATION, TEXAS ) PSYCHIATRIC CO., INC.. A/K/A ) 13 AND/OR D/B/A HCA BEAUMONT ) NEUROLOGICAL HOSPITAL, AND HCA ) 14 HEALTH SERVICES OF TEXAS, INC. ) 128TH JUDICIAL A/K/A AND/OR BEAUMONT ) DISTRICT 15 NEUROLOGICAL HOSPITAL ) Page 3 1 * * * * * * * * * * 2 IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS COUNTY DEPARTMENT - LAW DIVISION 3 RENATO DI SILVESTRO, Individually ) 4 and as Special Administrator of ) the Estate of JOHN DI SILVESTRO, ) 5 Deceased, ) ) 6 Plaintiff, ) ) 7 v. ) No. 91 L 7881 ) 8 ROBERT L. NELSON, et al., ) ) 9 Defendants, ) ) 10 GEORGE MELNICK, M.D. and PETER ) FINK, M.D. ) 11 ) Respondents in Discovery.) 12 * * * * * * * * * * Page 4 1 IN THE CIRCUIT COURT OF THE SIXTH JUDICIAL CIRCUIT CHAMPAIGN COUNTY, ILLINOIS 2 LINDA GARDNER, Individually and ) 3 as Special Administrator of ) the Estate of SHANE GARDNER, ) 4 deceased, ) ) 5 Plaintiff, ) ) 6 v. ) No. 91 L 1066 ) 7 ELI LILLY AND COMPANY, a foreign ) corporation, ) 8 ) Defendant. ) 9 10 * * * * * * * * * * Page 5 1 SUPERIOR COURT OF THE STATE OF CALIFORNIA 2 FOR THE COUNTY OF LOS ANGELES 3 DR. MARIUS SAINES, etc., et al., ) Case No: 4 ) SC 008331 Plaintiffs, ) 5 ) vs. ) 6 ) ELI LILLY & COMPANY, a corporation; ) 7 DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1- ) 8 100, inclusive, ) ) 9 Defendants. ) ____________________________________) 10 11 * * * * * * * * * * 12 NO. 93-8792-D 13 DAVID KUNG, DALE KUNG COHEN ) IN THE DISTRICT ROBERT KUNG, AND TIMOTHY KUNG, ) COURT OF 14 INDIVIDUALLY AND AS SURVIVORS ) AND STATUTORY BENEFICIARIES ) 15 OF MAY YUN KUNG, DECEASED ) ) 16 VS. ) DALLAS COUNTY ) T E X A S 17 ELI LILLY AND COMPANY, DISTA ) PRODUCTS COMPANY, AND MONIQUE ) 18 KUNKLE, PH.D. ) Page 6 1 * * * * * * * * * * 2 IN THE DISTRICT COURT OF JOHNSON COUNTY, KANSAS 3 CIVIL COURT DEPARTMENT 4 EUGENE HUSLIG, AS ADMINISTRATOR ) 5 AND EXECUTOR AND ON BEHALF OF ) THE ESTATE OF DEBORAH G. WEATHERS ) 6 HUSLIG, DESCEASED, AND AS SURVIVING ) HUSBAND AND HEIR AT LAW OF DEBORAH ) 7 G. WEATHERS HUSLIG, DECEASED, ) AND IN HIS INDIVIDUAL CAPACITY AS ) 8 HUSBAND OF DEBORAH G. WEATHERS ) HUSLIG, DECEASED, AND RONALD C. ) 9 WEATHERS, SON OF DEBORAH G. ) WEATHERS HUSLIG, DECEASED, ) CASE NO.: 10 ) 94 C 192 PLAINTIFFS, ) 11 ) VS. ) 12 ) COURT NO. 7 MARY L. BILLINGSLEY, EXECUTOR OF ) CHAPTER 60 13 THE ESTATE OF THAD BILLINGSLEY, ) M.D., DECEASED D/B/A THE BENESSERE ) 14 CENTER, SUSAN C. JOHNSON, PH.D., ) BILLINGSLEY ENTERPRISES, INC., ) 15 F/K/A THAD H. BILLINGSLEY, M.D. ) CHARTERED, D/B/A THE BENESSERE ) 16 CENTER, ELI LILLY AND COMPANY, ) AND DISTA PRODUCTS COMPANY, ) 17 ) DEFENDANTS. ) Page 7 1 * * * * * * * * * * 2 3 CAUSE NO. 93-04911-A 4 LINDA JILL WELCH, CARLINDA 5 WELCH REX, CONNAN ROSS WELCH AND CHAD MICHAEL WELCH, 6 INDIVIDUALLY AND AS SURVIVORS AND STATUTORY BENEFICIARIES 7 OF CARL EUGENE WELCH, DECEASED PLAINTIFFS 8 V. 9 ELI LILLY AND COMPANY, DISTA PRODUCTS COMPANY, NOE NEAVES, 10 M.D., AND MINITH-MEIER CLINIC, P.A. DEFENDANTS Page 8 1 THE DEPOSITION OF DR. HANS WEBER, TAKEN AT 2 THE OFFICE OF BAKER & DANIELS, 300 NORTH MERIDIAN 3 STREET, SUITE 2700, INDIANAPOLIS, INDIANA 46204, 4 ON SEPTEMBER 10, 1992; SAID DEPOSITION TAKEN 5 PURSUANT TO NOTICE IN ACCORDANCE WITH THE RULES 6 OF CIVIL PROCEDURE. 7 * * * * * * * * * * 8 A P P E A R A N C E S 9 10 NANCY ZETTLER COUNSEL FOR PLAINTIFFS 11 1405 WEST NORWELL LANE SCHAUMBURG, ILLINOIS 60193 12 PAUL SMITH 13 COUNSEL FOR PLAINTIFFS 745 CAMPBELL CENTER 2 14 8115 NORTH CENTRAL EXPRESSWAY DALLAS, TEXAS 75206 15 LAWRENCE J. MYERS 16 STEVE LORE COUNSEL FOR ELI LILLY AND COMPANY 17 FREEMAN & HAWKINS 4000 ONE PEACHTREE CENTER 18 303 PEACHTREE STREET, N.E. ATLANTA, GEORGIA 30308-3243 19 MARGARET M. HUFF 20 ELI LILLY AND COMPANY LILLY CORPORATE CENTER 21 INDIANAPOLIS, INDIANA 46285 Page 9 1 ALLISON SPRUILL COUNSEL FOR BEAUMONT NEUROLOGICAL HOSPITAL 2 BARTLETT & FRIEND, LLP 1301 MCKINNEY, SUITE 2900 3 HOUSTON, TEXAS 77010 Page 10 1 I N D E X 2 3 DEPOSITION OF DR. HANS WEBER 4 5 DIRECT EXAMINATION BY MR. SMITH 12 6 7 CERTIFICATE 261 8 ERRATA 262 9 10 EXHIBITS 11 PLAINTIFFS' EXHIBIT NO. 1.................105 PLAINTIFFS' EXHIBIT NO. 2.................121 12 PLAINTIFFS' EXHIBIT NO. 3.................132 PLAINTIFFS' EXHIBIT NO. 4.................144 13 PLAINTIFFS' EXHIBIT NO. 5.................197 PLAINTIFFS' EXHIBIT NO. 6.................212 14 PLAINTIFFS' EXHIBIT NO. 7.................233 PLAINTIFFS' EXHIBIT NO. 8.................248 15 PLAINTIFFS' EXHIBIT NO. 9.................252 Page 11 1 2 VIDEOGRAPHER: Today's date is 3 September 10, 1994. We're in Indianapolis, 4 Indiana taking the deposition of Doctor Hans 5 Weber. The approximate time is close to 9:15 6 a.m. local time. This is Marty Hoyle, Legal 7 Video Services, Indianapolis, Indiana. 8 COMES DOCTOR HANS WEBER, CALLED BY THE 9 PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, WAS 10 DEPOSED AND TESTIFIED AS FOLLOWS: 11 DIRECT EXAMINATION 12 BY MR. SMITH: 13 Q. Would you state your name 14 please, sir. 15 A. My name is Hans Weber. 16 Q. Doctor Weber, my name is Paul 17 Smith, I'm from Dallas, Texas and I'm here to 18 take your deposition in a number of lawsuits 19 involving the antidepressant medication Prozac. 20 Do you understand that? 21 A. Yes, of course. 22 Q. Are you a United States 23 citizen? 24 A. No, sir, no. Page 12 1 Q. Do you speak English? 2 A. Yes. 3 Q. Do you read English? 4 A. Yes. 5 Q. What is your native tongue, 6 sir? 7 A. German. 8 Q. And how old a man are you? 9 A. How old? 10 Q. How old a man are you? 11 A. I'm fifty years. 12 Q. Fifty-six? 13 A. Fifty. 14 Q. Do you have any difficulty in 15 understanding me, sir, as I speak English to you? 16 A. No, it sounds fine to me. 17 Q. How long have you spoken 18 English? 19 A. I learned it at school and 20 then of course I had to read medical literature 21 in English because most of the publications are 22 in English anyway. And I came over to the United 23 States for two and a half years where I trained 24 to use the English in practice. Page 13 1 Q. Do you feel comfortable 2 conversing with me in English? 3 A. Yes, I feel comfortable. 4 Q. Do you feel that you have an 5 adequate ability to express your knowledge 6 concerning fluoxetine hydrochloride and your 7 dealings with that product to the jury in this 8 case in English? 9 A. Yes, I do. 10 Q. Doctor Weber, we have a German 11 interpreter here who can translate my English 12 into German and direct those questions to you in 13 German and make you better able to understand my 14 question if you think it's necessary. 15 A. Uh-huh. 16 Q. Do you think it's necessary 17 that there be an interpreter here to turn my 18 English questions into German questions so that 19 you can better understand them? 20 A. I do not think that it is 21 necessary. 22 Q. Do you think that you're able 23 to express your answers to my questions in 24 English appropriately where you would not need to Page 14 1 have the assistance of the German interpreter 2 here to turn your German answer into English for 3 me? 4 A. Yes, I think I can do so. 5 Q. Do you have any reason to 6 believe that you and I cannot communicate in 7 English today in a manner that will express your 8 views to me, answer your questions to me and you 9 be able to understand the questions I propose to 10 you in English? 11 A. Up to now it seems to me just 12 fine. 13 Q. Do you foresee that there 14 would be any problem in understanding an English 15 word that I might use? 16 A. Well, there may be one word, 17 but in ninety-nine percent I think I am okay. 18 Q. When you talk with the 19 scientists here at Eli Lilly and Company in 20 Indianapolis, do you communicate with those 21 scientists in English? 22 A. Yes, because they don't speak 23 German. 24 Q. Are you able to communicate to Page 15 1 the scientists here in Indianapolis your views 2 concerning matters of medicine and safety and 3 efficacy of antidepressant treatment in English 4 to them? 5 A. Yes, we do this all the time. 6 Q. And have you ever had any 7 instance where the scientists here in 8 Indianapolis with Eli Lilly and Company have 9 expressed to you an inability to communicate with 10 you in the English language? 11 A. No, there was no difficulty at 12 all. Sometimes it needs a little bit more 13 patience. 14 Q. Obviously, you speak with a 15 German accent, as I speak with a Texas accent. 16 A. Yes. 17 Q. But we have Ms. Zettler here 18 from Chicago, if you need English transmitted to 19 you in upper Midwestern accent, she can certainly 20 do that. 21 A. Yes. Sometimes the 22 translation from Texan English to English might 23 be necessary. 24 Q. Then we also have Mister Myers Page 16 1 here who can translate into Georgia English if 2 necessary, correct? 3 A. All right. 4 Q. And our court reporter taking 5 down our written record is from Louisville, 6 Kentucky, where some of this litigation will be 7 held, and certainly if she -- you don't feel you 8 are going to have any difficulty communicating to 9 her, do you? 10 A. No. 11 (DISCUSSION OFF THE RECORD.) 12 Q. Doctor Weber, to ensure that 13 our court reporter is able to understand your 14 accent, we're going to ask the translater to 15 remain present in the room for the time being, 16 but not actually translate anything unless our 17 court reporter has difficulty in understanding 18 your German accent. Apparently that's the only 19 problem that we've come with so far, all right? 20 A. That's fine. 21 Q. If at any time I use any 22 phrase or term or pronounce a phrase or term in a 23 manner that you don't understand, please feel 24 free to ask me to repeat it or restate it and I Page 17 1 will be glad to do that, all right? 2 A. I'll let you know. 3 Q. These are important procedures 4 concerning important matters and it is basic that 5 you and I be able to communicate, all right? 6 A. (Witness moves head up and 7 down.) 8 Q. Have you had an opportunity, 9 Doctor Weber, to discuss a deposition and your 10 deposition here today with Lilly attorneys? 11 A. Yes, I have. 12 Q. When did you first discuss 13 this deposition today? 14 A. It was mentioned I think about 15 half a year ago. 16 Q. Six months ago? 17 A. Yes, said it might happen. 18 But it was not clear at this point in time. 19 Q. Did you have a meeting with a 20 Lilly lawyer to discuss the possibility of your 21 deposition? 22 A. I did not have a meeting with 23 a Lilly lawyer, no, but I had discussions on the 24 phone and on video conference. Page 18 1 Q. On media conference? 2 A. Right. 3 Q. Who was present on that media 4 conference? 5 A. Mary Huff and also the 6 external lawyers. 7 Q. Mister Myers? 8 A. Yes. 9 Q. Larry Myers? 10 A. Yes. 11 Q. Any other external lawyers 12 present? 13 A. Peter Lore as well. 14 Q. Beg your pardon? 15 A. Peter Lore as well. 16 Q. Steve Lore. 17 A. Steve Lore. 18 Q. And how long did that 19 discussion entail? 20 A. We discussed all together 21 three half days, three afternoons. 22 Q. You had three separate 23 discussions on three afternoons, is that correct? 24 A. That is correct. Page 19 1 Q. And you had a video 2 teleconference? 3 A. At most of the conferences, 4 yes. 5 Q. And this was some satellite 6 communication with video -- 7 A. Right. 8 Q. -- where they could see you 9 and you could see them? 10 A. That is right. 11 Q. But that was disappointing for 12 you to see actually Mister Myers and Mister Lore, 13 was it not? 14 A. No, it was not disappointing, 15 no. 16 MR. MYERS: Mister Lore was inanimate 17 most of the time, anyway. 18 Q. Did you review any documents 19 at that meeting -- at any of those meetings? 20 A. At this meeting we talked 21 about some documents, yes. 22 Q. Did they have documents 23 present in front of them and you had documents 24 present in front of you? Page 20 1 A. Yes, they had some documents 2 present in front of them. I had two -- for 3 example, the labeling of Prozac. Or as we call 4 it in Germany, Fluctin. 5 Q. Any other communications that 6 you had with them? 7 A. I had also communication with 8 Steve Lore and Larry Myers directly, we had a 9 meeting in Atlanta. 10 Q. When was that, sir? 11 A. That was last Monday. 12 Q. And how long did that meeting 13 last? 14 A. One day. 15 Q. Was it at their law office? 16 A. Yes. 17 Q. And did you review documents 18 at that time, Doctor Weber? 19 A. Yes, we reviewed some 20 documents, communication between Indianapolis and 21 Bad Homburg office, for example. 22 Q. And that meeting lasted all 23 day last Monday? 24 A. Yes. Page 21 1 Q. Have you had any other 2 meetings with any lawyers since Monday? 3 A. No. 4 Q. Now, have you met with any 5 Lilly employees prior to today to discuss your 6 testimony? 7 A. No. 8 Q. Have you reviewed any 9 depositions that have been previously given by 10 anyone in these cases? 11 A. No, I have not. 12 Q. Did you come to the United 13 States from Germany? 14 A. Yes, that's right. 15 Q. When did you come to the 16 United States? 17 A. Last Sunday, Sunday one week 18 ago. 19 Q. Okay. So today is Saturday, 20 so tomorrow you will have been here one week? 21 A. That is right. 22 Q. And I assume you flew from 23 Germany directly to Atlanta -- 24 A. Yes. Page 22 1 Q. -- since you met with Mister 2 Myers and Mister Lore in Atlanta on Monday? 3 A. Yes. 4 Q. And then what have you done 5 the rest of this week? 6 A. We had a business meeting here 7 in Indianapolis. 8 Q. What was the nature of that 9 business meeting? 10 A. That was planning for the next 11 year. 12 Q. And was that a meeting that 13 had been scheduled? 14 A. Yes, that was a scheduled 15 meeting. 16 Q. How long had that meeting been 17 scheduled? 18 A. A year. That is a standing 19 meeting for some years now. 20 Q. What is the name of that 21 meeting? 22 A. That is a kind of global 23 medical director meeting, especially for the 24 purpose of business planning. Page 23 1 Q. Are there any other 2 individuals from the German affiliate here for 3 that meeting? 4 A. Yes, yes. 5 Q. Who, please, sir? 6 A. There are two clinical 7 research managers here. 8 Q. May I have their names, 9 please? 10 A. The names are Karl Peter 11 Menges. 12 Q. Can you spell his last name 13 for us, please? 14 A. M-E-N-G-E-S. And there was 15 Joachim Uekermann. Shall I spell both names? 16 Q. Please. 17 A. J-O-A-C-H-I-M. And the second 18 name is U-E-K-E-R-M-A-N-N. 19 Q. Anybody else from the German 20 office here? 21 A. Well, we have a related office 22 in Homburg which is Basingstoke Lilly, and the 23 medical manager from Basingstoke also was here. 24 Q. Who is that, sir? Page 24 1 A. Who is Holger Schilske. 2 H-O-L-G-E-R is the first name, and the second 3 name is S-C-H-I-L-S-K-E. 4 Q. How long will this meeting 5 last, sir? 6 A. That is -- it lasted until 7 yesterday evening. 8 Q. Do you know a Doctor 9 Schulze-Solce? 10 A. Yes. 11 Q. Who is Doctor Schulze-Solce? 12 A. Doctor Schulze-Solce is a 13 research director in Japan. He has been a former 14 employee of Lilly Germany. 15 Q. And have you met with him? 16 A. Yes, he was at the meeting as 17 well. 18 Q. He's been at this meeting this 19 entire week? 20 A. Yes, yes. 21 Q. Did you -- when did you first 22 see -- was Doctor Schulze-Solce at the Atlanta 23 meeting on Monday? 24 A. No, no. Page 25 1 Q. But did you see Doctor 2 Schulze-Solce here this week in Indianapolis? 3 A. Yes, I did see him here. 4 Q. When did Doctor Schulze-Solce 5 leave Germany? 6 A. Beginning of 1990. 7 Q. Okay. Let's back up and get 8 some background. 9 A. Uh-huh. 10 Q. Describe for me, Doctor Weber, 11 your educational background starting with high 12 school, when and where you graduated from high 13 school. 14 A. I graduated from high school 15 in Aurich. That's something to spell, 16 A-U-R-I-C-H, which is in northern part of 17 Germany. And from there, I went to medical 18 school at the Free University of Berlin. As a 19 medical education, I had at the University of 20 Innsbruck, which is in Austria, the University 21 Frankfort, and later I returned to the Free 22 University of Berlin to take the medical 23 examination. 24 Q. All right. When did you get Page 26 1 your medical doctor degree as we know it here in 2 the United States? 3 A. Medical doctor degree was 4 probably in '79. 5 Q. And was that conferred on you 6 by the University of Berlin? 7 A. Yes, uh-huh. 8 Q. Was your medical training 9 similar to that medical training that medical 10 doctors here in the United States get? 11 A. Wait a minute, it was not in 12 '79, it was in '68 that I got my medical degree. 13 The question whether it's similar to the United 14 States, I think there are differences in 15 education. We have -- our medical education 16 takes all together six years, while I think it is 17 a little bit shorter in the United States, and in 18 the United States you have first a bachelor 19 degree and then go to medical education. But I 20 think the content is really the same. 21 Q. If you were an internist in 22 Germany, trained as an internist in Germany, 23 would your knowledge of internal medicine be 24 similar to an internist in the United States Page 27 1 trained in the United States? 2 A. I think that is comparable, 3 yes. 4 Q. A general surgeon in Germany, 5 would his training be similar to the training a 6 general surgeon receives in the United States? 7 A. Yes, I think so. 8 Q. In other words there's a 9 period of time when you go through course work, 10 you do lab work, you do some type of clinical 11 work? 12 A. Yes. 13 Q. And then take examinations? 14 A. Yes. I think that the 15 practical training on the patient bed is you do 16 more in the United States than in Germany, in 17 Germany you learn it a little bit later. But 18 after all when you are a specialist in the area 19 of internal medicine, it's really the same. 20 Q. Do you have any specialty as a 21 physician? 22 A. Yes, I'm a specialist in 23 internal medicine, and I'm particularly trained 24 in cardiology and intensive care medicine. Page 28 1 Q. Would your knowledge of 2 internal medicine and cardiology and intensive 3 care be similar to that knowledge possessed by 4 internal medicine specialists who do cardiology 5 and intensive care here in the United States? 6 A. I would say yes. 7 Q. There's no differences in the 8 anatomy of a German versus a citizen of the 9 United States, is there? 10 A. Not that I'm aware of, no. 11 Q. There's no differences in the 12 physiology of a German versus a citizen of the 13 United States, is there? 14 A. No. 15 Q. We are homo sapiens, human 16 beings, wherever we reside, is that right? 17 A. On both sides of the Atlantic, 18 right. However, there are sometimes a little bit 19 differences in medical practice in the United 20 States or in Germany. For example, when you 21 treat bronchitis or asthma particularly, then the 22 treatment might be different in the United States 23 compared to some European countries. 24 Q. I understand that there may be Page 29 1 different schools of thought concerning methods 2 of treatment. 3 A. That's right. 4 Q. But right now I'm talking with 5 you, Doctor Weber, about human beings. 6 A. Oh, that's absolutely -- well, 7 that's absolutely the same. 8 Q. If -- you're a German citizen, 9 correct? 10 A. Right. 11 Q. I'm a citizen of the United 12 States. If somebody were to draw blood from each 13 of us -- 14 A. Uh-huh. 15 Q. -- they would not be able to 16 tell any differences in our blood according to 17 nationality, would they? 18 A. That's right, they cannot 19 separate, no. 20 Q. If I were sick with an 21 infection -- 22 A. Uh-huh. 23 Q. -- that infection would be the 24 same type of infection regardless of where that Page 30 1 infection is, correct? 2 A. That is right, uh-huh. 3 Q. If I were suffering from a 4 mental illness -- 5 A. Uh-huh. 6 Q. -- I would have the same signs 7 and symptoms wherever I resided, would I not? 8 A. Certainly, yes. 9 Q. My citizenship doesn't affect 10 my physical health, does it? 11 A. No. 12 Q. An individual who is depressed 13 in Germany presents the same physiological 14 characteristics as an individual who is depressed 15 in the United States. 16 A. I would think so, yes. 17 Q. When was it, Doctor Weber, 18 that you became particularly trained in internal 19 medicine? 20 A. That was after I made my -- 21 completed my medical school, between '68 -- well, 22 I started this pharmacology actually, became 23 first training in clinical pharmacology until 24 about 1973, and after this time went to the Page 31 1 hospital, the Free University again, to get the 2 training in internal medicine, cardiology and 3 intensive care. 4 Q. Did you receive some type of 5 certification or recognition of special 6 competence in that area? 7 A. Yes. I received a 8 certification in clinical pharmacology and 9 internal medicine, yes. 10 Q. Tell me when you received a 11 certification in clinical pharmacology, sir? 12 A. Roughly '78, '79, at this time -- 13 no, excuse me, it was probably in '81. 14 Q. And when did you receive a 15 certification in internal medicine? 16 A. That was also around this 17 time, '81. 18 Q. Did you do both at the same 19 time, receive that certification and do those 20 studies both at the same time? 21 A. Well, the education in 22 clinical pharmacology was earlier, but I applied 23 for the certification for both of them at the 24 same time, yes. Page 32 1 Q. Doctor Weber, as a clinical 2 pharmacologist certified in clinical pharmacology 3 in Germany -- 4 A. Uh-huh. 5 Q. -- do you know of any 6 different pharmacological reaction that 7 fluoxetine hydrochloride has in human beings 8 regardless of where they live? 9 A. There should not be any 10 difference, no. 11 Q. Does the mode of action of 12 Prozac, fluoxetine hydrochloride, work the same 13 way in Germany as in the United States? 14 A. Yes, it does. 15 Q. In other words the theory of 16 fluoxetine hydrochloride is that it inhibits the 17 reuptake of serotonin, is that correct? 18 A. That is applicable for both 19 sides of the ocean, yes. 20 Q. And it should do so in the 21 same manner regardless of where a person lives. 22 A. Absolutely, yes. 23 Q. Or of their national origin. 24 A. Yes, you're right. Page 33 1 Q. All right. Tell us -- have 2 you received any other type of certifications or 3 certificates of special competence in any other 4 areas of medicine? 5 A. No, no. 6 Q. Tell me about your employment 7 background, Doctor Weber. You're currently 8 employed by Eli Lilly and Company, are you not? 9 A. Yes, uh-huh. 10 Q. What is your title with Eli 11 Lilly and Company? 12 A. Medical director for the 13 German affiliate. 14 Q. Does the German affiliate have 15 a particular name? 16 A. Lilly Deutchland, GMBH. 17 Q. This GMBH, is that the 18 equivalent of an I-N-C incorporation or company 19 here? 20 A. Yes. 21 Q. When did you begin your 22 employment with Eli Lilly and Company, Doctor 23 Weber? 24 A. That was in '82. Page 34 1 Q. And have you been continuously 2 employed by Lilly since 1982? 3 A. Yes, that's right, since that 4 time. 5 Q. Prior to beginning working for 6 Eli Lilly and Company, where did you work, sir? 7 A. At the Free University of 8 Berlin. 9 Q. And how were you employed at 10 the Free University of Berlin? 11 A. As a physician. 12 Q. Were you employed by that 13 university? 14 A. Yes, uh-huh. 15 Q. What was your job there? 16 A. I was a practicing physician 17 in internal medicine, intensive care and 18 cardiology. 19 Q. So you were a working doctor 20 as we say? 21 A. Yes, that's right. 22 Q. Seeing patients? 23 A. Seeing patients, yes. 24 Q. Treating patients who were Page 35 1 ill. 2 A. That's right. 3 Q. Administering medication. 4 A. Yes. 5 Q. And issuing orders concerning 6 appropriate medical treatment for individuals who 7 needed medical care at the Free University of 8 Berlin. 9 A. That is right, uh-huh. 10 Q. How long did you do that, sir? 11 A. Let me remember. Six years, I 12 think, about six years. 13 Q. So would that mean that you 14 started working at the Free University of Berlin 15 somewhere like in 1976? 16 A. Let me get the sequence right. 17 After stopping the medical school, either in '68 18 or '69, I do not remember exactly, I did 19 pharmacology for three years, I think it was 20 until '73, and then I started to be a physician 21 at a small hospital in Berlin. Do you want the 22 name of this hospital? 23 Q. Please. 24 A. St. Hildegarde Hospital, S-T Page 36 1 point, H-I-L-D-E-G-A-R-D, St. Hildegard Hospital 2 in Berlin. And after one and a half year, means 3 in '75, I went to the Free University of Berlin 4 in internal medicine, and there I got my degrees 5 of clinical pharmacology and internal medicine in 6 '81 and then I started for Lilly in '82. 7 Q. But basically you were in what 8 we would call here in the United States private 9 practice from 1973 until 1982 when you joined 10 Lilly? 11 A. No, not private practice, it 12 was hospital located physician. 13 Q. All right. Are there 14 physicians in Germany who have private practices 15 similar to those physicians here in the United 16 States? 17 A. I'm not exactly aware of what 18 private practice here is, but I think it is 19 comparable, yes. We have private practice, yes. 20 Q. But your practice of medicine 21 was limited to hospital settings, is that right? 22 A. That's right, I did not -- 23 have not been in the private practice. 24 Q. In other words, as a physician Page 37 1 you were on a full-time salary -- 2 A. Yes. 3 Q. -- with a hospital? 4 A. Yes, yes. 5 Q. As opposed to being paid 6 directly by patients per office visit like some 7 physicians are. 8 A. That's right, I was paid by 9 the hospital, yes. 10 Q. Did any of that period of time 11 up until the time you joined Lilly -- after you 12 got out of medical school in '68 up to 1982, are 13 you with me? 14 A. Yes. 15 Q. Did you do any clinical 16 research during that time? 17 A. Yes, uh-huh. 18 Q. Tell me what clinical research 19 you did, sir. 20 A. I started -- I performed 21 clinical trials on antibiotics, I did testing of 22 nutrition in intensive care patients, I studied 23 metabolism in intensive care patients. 24 Q. What was that, medicalism? Page 38 1 A. Metabolism. 2 Q. Metabolism. 3 A. Sorry, metabolism. And I then 4 went into cardiovascular research, especially 5 intracoronary thrombolysis after myocardyal 6 infarction. 7 Q. Any other research? 8 A. All that has been. 9 Q. The clinical trials that you 10 did on the antibiotics -- 11 A. Uh-huh. 12 Q. -- for what manufacturer were 13 you involved? 14 A. Several manufacturers. 15 Q. Name them, if you can. 16 A. Hoechst, H-O-E-C-H-S-T, that's 17 a big company in Germany, Fresenius, F-R-E-N-E -- 18 sorry, start again. F-R-E-S-E-N-I-U-S, and 19 Lilly, L-I-L-L-Y. 20 Q. What Lilly clinical trials 21 were you involved in? 22 A. Antibiotics, Tobramycin at 23 this point in time. 24 Q. Was that the only Lilly drug Page 39 1 that you investigated? 2 A. Yes, yes, it was. 3 Q. And what was your function in 4 investigating Tobramycin for Lilly, were you a 5 clinical investigator, were you a research 6 physician, what were your duties in that 7 connection? 8 A. Yes, I was a clinical 9 investigator to study intratrachial application 10 of Tobramycin. 11 Q. Were you the principle 12 investigator on a particular study? 13 A. Yes, on this particular study 14 I was the principle investigator. 15 Q. How many patients did that 16 study include that you were involved in? 17 A. Long time ago, but I think 18 about twenty. 19 Q. Since it was a long time ago, 20 can you give us approximately when that clinical 21 trial occurred? 22 A. Approximately I can tell it to 23 you, it was around '76 to '78, in this time 24 frame. Page 40 1 Q. Did you deal with Lilly 2 Indianapolis during that trial or did you deal 3 with -- 4 A. No, this local Lilly. 5 Q. All right. And is that the 6 same local Lilly for whom you are now employed? 7 A. Yes, uh-huh. 8 Q. Was it in Bad Homburg at that 9 time? 10 A. Yes. 11 Q. You mentioned Hoechst, 12 correct? 13 MS. ZETTLER: Hoechst. 14 A. Hoechst, yes. 15 Q. They have in the past done 16 some marketing for the Lilly affiliate in 17 Germany, have they not? 18 A. Yes, they have. 19 Q. Did you do any clinical trials 20 or any clinical research for that entity 21 concerning Lilly products under investigation? 22 A. No, no, no. 23 Q. Have you ever done any 24 clinical research in connection with any Page 41 1 antidepressant manufactured by any pharmaceutical 2 firm? 3 A. No. 4 Q. Are you a psychiatrist? 5 A. No, I'm not. 6 Q. Are you a psychologist? 7 A. No. 8 Q. Are you trained as a 9 psychiatrist or psychologist, whether you be 10 practicing? 11 A. What is normal during medical 12 education, but nothing in particular, no. 13 Q. Have you ever treated 14 individuals for a psychiatric illness? 15 A. Well, I spent two months in a 16 psychiatric hospital, but as a supervision of 17 psychiatric. So there I was trained, but I did 18 not treat any patient by myself, no. 19 Q. Was that part of what we call 20 here in the United States a rotating internship 21 or something of that nature? 22 A. Yes, something of this nature, 23 yes, uh-huh. 24 Q. And you became somewhat Page 42 1 acquainted with individuals with psychiatric 2 illnesses, is that right? 3 A. That is right, for two months, 4 yes. 5 Q. But as far as being the 6 physician responsible for their care, you've 7 never done that? 8 A. That's right, uh-huh. 9 Q. Have you ever cared for an 10 individual who was suffering from depression? 11 A. No. 12 Q. I would assume that you, since 13 you are an internist basically -- 14 A. Yes. 15 Q. -- that in your hospital 16 practice you saw patients who had internal 17 medicine problems who are also suffering from 18 varying degrees of mental illnesses, didn't you? 19 A. Yes, that is right. 20 Q. And how would you treat the 21 psychiatric aspects of their problems? 22 A. Call an expert. 23 Q. What kind of experts would you 24 call in? Page 43 1 A. A psychiatrist. 2 Q. Why would you do that, sir? 3 A. Well, since I'm not 4 specialized in this area, a specialist should 5 take care of the patient. 6 Q. Did you ever order without a 7 psychiatric consult as an internist any 8 psychiatric medications for a patient? 9 A. It depends what you call 10 psychiatric medication. Anxiolytics, yes. 11 Q. Something such as Valium, 12 benzodiazepines -- 13 A. That is right, that is 14 correct. 15 Q. -- for anxiety? 16 A. Yes, that is right. 17 Q. Obviously individuals who had 18 had heart attacks who you've treated suffer from 19 anxiety, do they not? 20 A. Yes, and they received 21 benzodiazepines. 22 Q. How about antidepressants, 23 have you ever prescribed antidepressants for any 24 of these patients that you've been treating? Page 44 1 A. I do not remember this, no, I 2 don't think so. 3 Q. Did you ever call in 4 psychiatric experts who administered or ordered 5 antidepressant medicines for those patients for 6 whom you were seeing for medical illnesses other 7 than their mental illness? Do you follow what 8 I'm saying? 9 A. No, repeat, please. 10 Q. Did you ever call in a 11 psychiatrist to prescribe an antidepressant for a 12 patient that you were treating for illnesses 13 unrelated to their depression? 14 A. Yes, that happened, right. 15 Q. Would that be your frequent 16 mode of operation in treating depressed 17 individuals that you saw in your practice, that 18 is call in a psychiatrist? 19 A. It happened regularly, 20 especially during the time when I was in 21 intensive care because there came many patients 22 with suicide attempts. 23 Q. All right. Do you consider 24 yourself an expert on depression? Page 45 1 A. No, no. 2 Q. Do you consider yourself an 3 expert on suicide? 4 A. No. 5 Q. Why did you join Lilly? 6 A. It can be a long answer or 7 short answer. Certainly I had to look after 8 being at the clinic -- Free University for six 9 years, I had to look for something else and I 10 choose to go to a pharmaceutical company, and 11 after a number of negotiations I decided to work 12 for Lilly. 13 Q. You say you had to leave the 14 Free University. Was there a certain term that 15 you served at the University? 16 A. Yes. As the contract which 17 you receive are restricted to a certain time 18 frame. 19 Q. You weren't forced to leave 20 the University by virtue of being fired or 21 anything, that's not what you're saying, is it, 22 sir? 23 A. No, no. 24 Q. What other options did you Page 46 1 have, could you have joined another hospital or 2 gone into private practice? 3 A. Well, I could have gone to 4 another hospital, I could have gone to a private 5 practice. There was also an opportunity to 6 prolong the contract with the Free University 7 perhaps in order to do more science, but I felt 8 that at this time -- point of time it was not an 9 option for me. 10 Q. What was your first job at 11 Lilly? 12 A. I was a clinical research 13 physician for antibiotics, infectious diseases. 14 Q. And you held that position 15 until when? 16 A. After one year I became 17 appointed to manager of clinical research and 18 then to medical director shortly thereafter. 19 Q. You've been medical director 20 ever since? 21 A. Well, I came to the United 22 States in between. 23 Q. Let's see if we can get this 24 straight then. You were a clinical research Page 47 1 physician from 1982 until 1983, correct? 2 A. Yes. 3 Q. Then you became manager of 4 clinical research? 5 A. Yes. 6 Q. And what years did you hold 7 that position, sir? 8 A. I think it was following that 9 in -- at the beginning of '83 already, I became 10 manager of clinical research, and in mid-'83 I 11 became director, medical director. 12 Q. All right. And how long were 13 you the medical director of the German affiliate? 14 A. Until -- 15 MR. MYERS: You mean the manager of 16 clinical research or medical director? 17 A. No, medical director. 18 MR. SMITH: Listen, Larry. We may 19 need you to translate for him. 20 A. Medical director until '87. 21 Q. All right. Is that when you 22 went to the United States? 23 A. Yes. 24 Q. And what job did you have here Page 48 1 with Lilly here in Indianapolis? 2 A. International medical advisor. 3 And that was for one and a half years, and then 4 for one year director of endocrinology. 5 Q. Here or in Germany? 6 A. Here in Indianapolis. And I 7 went back to Germany in -- I think it was in May, 8 '90 as a medical director. 9 Q. When you returned to Germany, 10 was your job duty as medical director basically 11 the same as that job you had in 1987 when you 12 left? 13 A. Yes. 14 Q. Why did you come to the United 15 States and have these two positions here? 16 A. Broaden experience, better 17 understanding of Lilly medical operations, 18 controlled in the United States. 19 Q. Was this something that you 20 wanted to do? 21 A. Yes. 22 Q. When you came to the United 23 States to have these two jobs, did you intend 24 that they would be on a temporary basis? Page 49 1 A. Yes. 2 Q. You knew when you left Germany 3 that you would be going back to Germany after a 4 period of time. 5 A. Right, it was my request to 6 say that I would come to the United States only 7 if I can go back after two to three years. 8 Q. Do you have a family, Doctor 9 Weber? 10 A. Yes. 11 Q. Wife and children? 12 A. Wife and three children. 13 Q. Did they accompany you here to 14 the United States? 15 A. Yes, they did. 16 Q. And they lived with you here 17 in Indianapolis? 18 A. That is right, yes. 19 Q. And then they returned with 20 you back to Germany? 21 A. Yes, and we returned for 22 private reasons. 23 Q. Beg your pardon? 24 A. Returned for private reasons. Page 50 1 Q. So you returned to Germany not 2 at Lilly's request but at your request? 3 A. Yes. 4 Q. Did it have anything to do 5 with your job or did it have something maybe to 6 do with the family? 7 A. It had to do with the family. 8 Q. Did you when you left Germany 9 to come to the United States know that when you 10 returned back to Germany that you would have the 11 same job title, medical director? 12 A. There is no other job title 13 available within medical and I did not want to 14 switch to another department other than medical, 15 yes. 16 Q. When you left Germany in 1987 17 as a medical director, who took your place? 18 A. Doctor Schulze-Solce. 19 Q. And when you came back to 20 Germany in 1990 as medical director, who did you 21 replace? 22 A. Doctor Schulze-Solce. 23 Q. What happened to him? 24 A. He went to Japan. Page 51 1 Q. Did he want to go to Japan? 2 A. He wanted to go somewhere else 3 and do something else, and Japan was one 4 opportunity. 5 Q. When you left the German 6 affiliate in 1987, who were the members of the 7 medical group there at the Lilly German 8 affiliate? You mentioned Doctor Schulze-Solce. 9 A. In '87? 10 Q. Yes. 11 A. Doctor Schulze-Solce, 12 Professor Peters. 13 Q. P-I-T-A-S? 14 A. P-E-T-E-R-S, yes. Who else 15 was there, Doctor Wettich, W-E-T-T-I-C-H. Well, 16 a number of clinical research associates, for 17 example the man, Joachim Uekermann was there. 18 Joachim Uekermann which I've spelled to you 19 before. 20 Q. We've seen various names in 21 connection with the German affiliate; we've seen 22 for instance Claude Bouchy's name. 23 A. Yes, he was general manager 24 and my boss when I left to the United States, and Page 52 1 also my boss when I returned. 2 Q. And when did he leave Lilly or 3 has he left Lilly? 4 A. He has left Lilly 5 approximately two to three years ago. 6 Q. And where did he go? 7 A. To a French company. 8 Q. What's the name of the French 9 company? 10 A. I've forgotten, I don't know. 11 Q. You've forgotten? 12 A. Yes. The name of the French 13 company which he left, it doesn't come to my 14 mind. I should know that, but it doesn't come to 15 my mind right now. 16 Q. I bet you'll think about it -- 17 A. It is in Lyon, and I know what 18 kind of company it is, but the name doesn't come 19 to me. 20 Q. Is Claude Bouchy a medical 21 doctor? 22 A. No, no, he's a businessman. 23 Q. You and he were friends? 24 A. We were friends? Page 53 1 Q. Yes. 2 A. No, we were not friends, but 3 we -- 4 Q. You didn't like each other? 5 A. We had a business relation and 6 I think we liked each other, yes, but friends I 7 would call something else. 8 Q. Have you kept in touch with 9 Claude Bouchy since he left Lilly? 10 A. Rarely. I think on -- I 11 talked to him after he left just to chat normal, 12 how is he doing, how are we doing and -- on two 13 occasions, actually I talked to him on the second 14 occasion, it was because I became aware of this 15 Prozac litigation. 16 Q. Okay. When was that? 17 A. Approximately half a year ago 18 when I first learned about it. 19 Q. Was this after you had this 20 telecommunication -- 21 A. No, no. 22 Q. -- with the lawyers? 23 A. No. The telecommunication I 24 had two or three weeks ago, so that was much Page 54 1 longer ago. 2 INTERPRETOR: Earlier. 3 THE WITNESS: Earlier, thank you. 4 Q. Okay. I thought that you had 5 this telecommunication conference with Mister 6 Myers and Mister Lore six months ago? 7 A. No, that was a wrong 8 understanding. I said that I learned that a 9 Prozac deposition may or may not come up from 10 Mary Huff and said it was approximately six 11 months ago, but we went into the specifics that I 12 was asked to come over, that was perhaps six 13 weeks ago or so. 14 Q. And that's when you had this 15 world wide telecommunication network set up where 16 you could see Mister Myers and he could see you? 17 A. Yes. 18 Q. That was six weeks ago? 19 A. No, that was now three weeks 20 ago. We then started to make this arrangement. 21 Q. But you talked to Doctor 22 Bouchy -- I'm sorry, you talked to Mister Bouchy 23 approximately six months ago when you first 24 learned about the Prozac litigation, is that Page 55 1 right? 2 A. Yes, that is right. I was 3 called to be informed that a Prozac litigation 4 may come up and that it might be required that 5 myself and Claude Bouchy show up, and I was asked 6 where Claude Bouchy has been gone, I delivered 7 his address and then I talked to him and told him 8 that this may come up. 9 Q. What is Mister Bouchy's 10 address, sir? 11 A. Lyon. 12 Q. Lyon, France? 13 A. In France, yes. 14 Q. Do you have his specific 15 address? 16 A. I can certainly find out, but 17 I have it not in the head -- in my head. 18 Q. But you gave that to Lilly 19 representatives six months ago when you called 20 Claude Bouchy? 21 A. I'm not sure about this. I 22 think what I did, I called Claude and told him 23 that a Prozac litigation may come up, and he said 24 he would find out about this. Page 56 1 Q. Okay. So you had a telephone 2 number for him -- 3 A. Yes. 4 Q. -- obviously to call him? 5 A. Yes, yes. 6 Q. You knew the city in which he 7 was located -- 8 A. Yes. 9 Q. -- at that time? 10 A. Yes. 11 Q. And you knew the company for 12 whom he was working at that time? 13 A. Yes, right. 14 Q. And did you have a street 15 address for that company at that time? 16 A. A street address, no, I don't 17 think so. 18 Q. Did you have a post office box 19 address or something? 20 A. We have it certainly in our 21 office. 22 Q. You had -- at all times you've 23 been able to locate Claude Bouchy? 24 A. Yes, uh-huh. Page 57 1 Q. Is that a yes? 2 A. Yes. 3 Q. And you've always had Claude 4 Bouchey's address there at your office in 5 Germany, correct, is that what you're saying? 6 A. At least his telephone number, 7 yes. 8 Q. And you didn't have any 9 difficulty six months ago when you called him in 10 getting his address, did you? 11 A. No, no. 12 Q. And do I understand you 13 correct, Doctor Weber, that after you obtained 14 his address you advised Lilly in Indianapolis of 15 his specific address? 16 A. That, I don't remember. 17 Q. They were -- Lilly in 18 Indianapolis was looking for Mister Bouchy, were 19 they not? 20 A. No, I'm not sure about this, I 21 don't know. The only thing was what I told you, 22 that I became aware that I myself and Mister 23 Bouchy may -- may be required to come to a Prozac 24 deposition. Page 58 1 Q. All right. And you called 2 Mister Bouchy and talked to him about that. 3 A. Yes. 4 Q. And did he say he would be 5 willing to come for a Prozac deposition? 6 A. I don't think that he was 7 interested to come. 8 Q. Q.0 What did he say about 9 that? 10 A. That he has very much to do 11 and that this is not on the list of his 12 priorities. 13 Q. Well, did he express to you at 14 that time that he felt like he had information 15 that if he were deposed would be harmful to 16 Lilly? 17 A. No, we did not talk about any 18 of this, no. 19 Q. Did you know that he had 20 information at that time that would be harmful to 21 Lilly, Doctor Weber? 22 MR. MYERS: Wait a minute. Before he 23 answers, let me object to the form of the 24 question. Go ahead and answer the question. Page 59 1 A. The answer is no. 2 Q. How long did that conversation 3 occur? 4 A. How long did this conversation -- 5 Q. When you talked to him on the 6 phone. 7 A. How long, four minutes. 8 Q. Four minutes? 9 A. Right. 10 Q. Were you timing it? 11 A. No, but let's say 12 approximately four minutes. It was short. 13 Q. Tell me as best you can 14 recall, Doctor Weber, the substance of that phone 15 conversation between you and Mister Bouchy. 16 A. Yes. The substance was I 17 called him and I said Mister Bouchy, I would like 18 to inform you that there is a Prozac litigation 19 is going on, it might be requested that you come 20 to the Prozac litigation, and I myself, too, and 21 I do not currently understand what is going on or 22 what it is all about. Claude asked me about 23 this, what is this all about, why should I occur, 24 is there a specific reason, do you know anything Page 60 1 about it, and I told him no, I don't know. And 2 that was the end of the conversation as it was 3 probably not -- he had so many things to do and 4 it was probably not on the list of his 5 priorities. But we left it totally open, what 6 happened after that, and I had no other 7 conversation with him after this phone call. 8 Q. Okay. That was the last time 9 you talked to him. 10 A. Yes. 11 Q. That was about six months ago. 12 A. About. 13 Q. And I believe you said you had 14 talked to him on one other occasion since he had 15 left Lilly? 16 A. Yes, it was earlier. 17 Q. All right. And what was the 18 substance of that conversation? 19 A. How he is doing, how business 20 is going in Germany with Eli Lilly, he was 21 interested about that. Just a chat between two 22 persons who have known for a long time. 23 Q. Where was he at that time? 24 A. In Lyon. Page 61 1 Q. And what was he doing at that 2 time? 3 A. He's general manager for this 4 French company. 5 Q. Have you thought of the name 6 of that French company yet? 7 A. It doesn't come up. It may be 8 Servier, but I'm not absolutely sure about it, 9 S-E-R-V-I-E-R. It's located in Lyon and they 10 have an affiliate in Strasbourg and another one 11 in Paris, but sorry I can't give you the address 12 and I'm not absolutely sure about the name. 13 Q. Is it a pharmaceutical firm, 14 sir? 15 A. Yes. 16 Q. What type of pharmaceuticals 17 do they manufacture? 18 A. What do they have? They have 19 anti -- lipid-lowering agents, for example, and I 20 think also some drugs which intervene with blood 21 clotting, thrombolysis. 22 Q. Do they have any 23 antidepressants or any psychiatric medications of 24 which you're aware? Page 62 1 A. I'm not aware, no. 2 Q. Are they actually a 3 manufacturer of drugs or are they a distributor? 4 A. Yes, uh-huh. 5 Q. Mister Bouchy is a 6 businessman? 7 A. A businessman, yes. 8 Q. He's not a scientist? 9 A. He is? 10 Q. He's not a scientist, is he? 11 A. No, he's not a scientist, no. 12 Q. Why did he leave Lilly? 13 A. He left two to three years ago 14 approximately. 15 Q. No, why did he leave? 16 A. Oh, why did he leave, sorry. 17 I do not exactly know why he left, but he got 18 certainly a very interesting offer to head this 19 company, this French company, which was probably 20 also interesting for him because he could go back 21 to France, he is from France originally. But I 22 do not know any other details around this. 23 Q. Doctor Weber, do you know if 24 he had any dissatisfaction whatsoever with Eli Page 63 1 Lilly and Company? 2 A. I think he was altogether very 3 pleased with Lilly and Company. I'm not sure 4 whether he was not a little bit disappointed 5 about his career at this point in time, but that 6 is pure speculation. 7 Q. He had expressed to you some 8 disappointment? 9 A. No. 10 Q. What do you base his 11 disappointment on then? 12 A. Well, he had been general 13 manager in Germany for some years and may have 14 wanted to go to another position, but as I said, 15 it is poor speculation and I think he had 16 probably more other reasons to leave the company. 17 Q. What other reasons? 18 A. That the new position 19 obviously was very promising to him, very good 20 shop, better than he had at Eli Lilly. 21 Q. How long was he with Lilly? 22 A. Quite a while, some years, but 23 I don't know exactly how many. 24 Q. Well, was he there when you Page 64 1 joined Lilly in 1982? 2 A. Not in Germany, no. 3 Q. Where was he? 4 A. I don't know whether he was 5 with Lilly at '82, but he was in France before he 6 came to Germany. 7 Q. Was it your understanding he 8 was with Lilly France before he came to Germany? 9 A. Yes. 10 Q. What is your general 11 impression with respect to how long Mister Bouchy 12 was employed by Eli Lilly and Company, Doctor 13 Weber? 14 A. How long he was -- 15 Q. Employed by Lilly in any 16 capacity. 17 A. Employed by Lilly, okay. No, 18 I can't answer this. 19 Q. Okay. We've also -- we got on 20 a long track there talking about Mister Bouchy, 21 but we were talking about other members of the 22 Lilly affiliate in Germany. 23 A. Yes. 24 Q. We've seen the name Johanna Page 65 1 Schenk. 2 A. Yes, uh-huh. 3 Q. Was she a member of the 4 medical team? 5 A. She was a member of the 6 medical team, but not at the time when I left. 7 She left the company some time earlier and I do 8 not exactly remember when it was, but around '84, 9 '85. 10 Q. Well, Doctor Schenk is a 11 medical doctor. 12 A. Yes. 13 Q. Or was. 14 A. Yes. 15 Q. Is Johanna Schenk a lady? 16 A. Yes, from Austria, which 17 explains a lot. 18 Q. Beg your pardon? 19 MS. ZETTLER: He said from Austria 20 which explains a lot. 21 Q. What does it explain? 22 A. No, no, just joking. 23 Q. Is that kind of like Polish 24 people? Page 66 1 A. No, we have a lot of 2 interesting things going on between Germans and 3 Austrians, we say we are very different. 4 MR. MYERS: It's like Dallas and 5 Houston. 6 Q. What is Doctor Schenk's 7 specialty? 8 A. She doesn't have a specialty, 9 she's a physician, M.D. 10 Q. She's a general practitioner? 11 A. Yes -- well, I think, but not 12 for absolutely sure. After she did get her 13 medical degree, she went directly to the 14 pharmaceutical industry. 15 Q. All right. And you say she 16 left in '84 or '85? 17 A. Around this time, yes. 18 Q. And did she go back to 19 Austria? 20 A. No, she went to another 21 company, to Bristol Myers, they're another name, 22 and got the position of a medical director there. 23 Q. Where? 24 A. At Bristol Myers. Page 67 1 Q. In Germany? 2 A. In Germany, yes. 3 Q. How long did she hold that job 4 or does she still hold that job? 5 A. No, she holds this job until 6 about two years ago, and is now the director of a 7 contract research organization, has a European 8 responsibility for the contract research 9 organization. 10 Q. What is the name of that 11 organization? 12 A. Quintiles. 13 Q. Can you spell that for me? 14 A. Q-U-I-N-T-I-L-E-S. It's an 15 American company by the way. 16 Q. And where is Quintiles 17 located, do you know? 18 A. Well, it's an American 19 company, the headquarters are here, but she's 20 located -- it's the same -- in the Frankfurt 21 area. Her husband is working for a television 22 company there, and therefore she always worked in 23 this area. 24 Q. What does her husband do, is Page 68 1 he a T.V. announcer? 2 A. He has something to do with 3 T.V., but I don't know what. 4 Q. All right. And do you still 5 speak with Doctor Schenk from time to time? 6 A. Yes, from time to time, yes. 7 Q. When did you last speak with 8 Doctor Schenk? 9 A. Quite a time now ago, probably 10 two years ago. I talked with her about this 11 contract research organization and if there would 12 be business to do between Quintiles and Eli 13 Lilly. 14 Q. And did you get something 15 going? 16 A. Not at this point of time, but 17 in the meantime there are -- Quintiles is doing 18 some work for Lilly, but not yet particularly in 19 Germany. 20 Q. Do you have Doctor Schenk's 21 phone number and address at Quintiles in 22 Frankfort? 23 A. Yes. 24 Q. You don't have it -- do you Page 69 1 have it off the top of your head? 2 A. No. 3 Q. Can you provide that -- 4 A. Yes. 5 Q. -- to the Lilly lawyers before 6 you leave? When are you scheduled to leave by 7 the way? 8 A. Today, today. 9 Q. All right. 10 A. No, I cannot because I would 11 have to call the office and the office is closed. 12 Q. How about maybe first part of 13 next week -- 14 A. Yes. 15 Q. -- E-mailing or faxing it 16 back? 17 A. I can do this. 18 Q. We've got some E-mail and fax 19 we'll show you in a minute. Use that same means 20 of communication. 21 MR. SMITH: Will you provide that to 22 us, Mister Myers? 23 MR. MYERS: Yes, sir. 24 MR. SMITH: Let's take a quick break. Page 70 1 (A SHORT RECESS WAS TAKEN.) 2 Q. (BY MR. SMITH) Doctor Weber, 3 have you been asked to come to the United States 4 to testify in any of these Prozac trials? 5 A. Not other than today, no. 6 Q. The Fentress versus Lilly case 7 is set for trial in Louisville, Kentucky 8 beginning on September 26th, which is two weeks 9 from next Monday. 10 A. Uh-huh. 11 Q. Have you been asked to come 12 testify in that case? 13 A. No, no. 14 Q. Do you have any plans to come 15 back to the United States to give live, in 16 person, testimony at trial of any Prozac related 17 lawsuits? 18 A. No, I have not. 19 Q. Would you do that if asked by 20 the Lilly lawyers? 21 A. If I'm requested to do so, 22 yes, uh-huh. 23 Q. Have the Lilly lawyers 24 discussed with you the possibility that they may Page 71 1 bring you to the United States to testify in any 2 cases? 3 A. No. 4 Q. Have they told you that you 5 will not be testifying? 6 A. No. 7 MR. SMITH: We need to make an 8 agreement in this deposition for the Fentress 9 case that we can use an unsworn copy at trial 10 since we're having to take his deposition late. 11 MR. MYERS: Well, we've reserved and 12 will reserve signature on the deposition and will 13 certainly expedite the turnaround of the review 14 of the deposition in order that there be a signed 15 copy available. If it becomes a question of 16 impossibility, I guess we'll have to take that 17 up, but what I'll tell you is we'll need a 18 transcript as soon as possible and we'll transmit 19 it to the witness for review and signature as 20 soon as possible to turn it around so that in 21 fact you'll have a signed copy. If we run into a 22 question of impossibility, we'll have to take 23 that up with the judge, but that's what I plan to 24 do. I plan to make every effort to expedite it. Page 72 1 MR. SMITH: Just so you understand 2 that we plan to use this deposition at trial, 3 regardless of whether it's signed. 4 MR. MYERS: I understand, I understand 5 that. 6 Q. When you were here in the 7 United States, Doctor Weber, did you practice any 8 medicine? 9 A. No. 10 Q. Did you do anything to comply 11 with the State of Indiana or any United States 12 requirements to be licensed to practice medicine 13 in any state within the United States? 14 A. No, no. 15 Q. Your function then when you 16 were with Lilly in the United States was simply 17 as a corporate employee and did not involve the 18 practice of medicine? 19 A. That is right. 20 Q. Before a new drug can be 21 marketed in Germany, does it have to be approved 22 by any regulatory body? 23 A. Yes, it has to be approved by 24 the BGA. Page 73 1 Q. Is that sort of the German 2 equivalent to the United States FDA? 3 A. Yes. 4 Q. Are they basically similar in 5 their requirements for approval of a drug? 6 MR. MYERS: Well, let me object to the 7 form of the question. Go ahead and answer. 8 A. There are differences. 9 Q. That wasn't my question. Are 10 they basically similar in the requirements? I'm 11 sure there are some differences, for instance the 12 differences would be written in different 13 languages -- the regulations would be different 14 languages. 15 MR. MYERS: Same objection, go ahead. 16 A. Was -- could you mention the 17 question again, sir? 18 Q. Well, let's cut to it. Does 19 the BGA require that the product be demonstrated 20 to be safe and efficacious in order to be 21 approved for use in Germany? 22 A. Yes. 23 Q. Are there certain specific 24 requirements that must be met in order for a drug Page 74 1 to be approved in Germany? 2 A. That might well be, depends 3 upon the drug, depends upon the disease. There 4 are certain differences between the United States 5 and the BGA, for example in the United States you 6 need two pivotal trials, while in Europe you only 7 need one pivotal trial. There are certain 8 differences, but regarding safety and efficacy, 9 it's the same. 10 Q. Both regulatory bodies are 11 examining the ultimate issue of the safety and 12 efficacy of the the drug, is that correct? 13 A. That is right or as we say in 14 Germany, benefit/risk ratio, yes. 15 Q. But benefit/risk ratio in 16 Germany is safety and efficacy in the United 17 States. 18 A. That is right. 19 Q. Both mean the same thing. 20 A. Yes. 21 Q. And they may have different 22 ways of getting to that issue, but the issue is 23 always going to be the same as far as the 24 ultimate decision that's going to be made? Page 75 1 A. Yes, it is the same, yes. 2 Q. We have heard mention of a 3 commission procedure in Germany. 4 A. Uh-huh. 5 Q. What is the commission 6 procedure in Germany with respect to the BGA and 7 the determination of safety and efficacy of a 8 drug in Germany? 9 A. Any drug which is going to be 10 approved in Germany is presented to an advisory 11 committee to the BGA which is a so-called 12 Commission A, and the members of Commission A who 13 are external experts give advice to the BGA 14 whether to approve the drug or not approve the 15 drug or to clarify specific questions. But it's 16 just an advisory role, the BGA makes the 17 decision. 18 Q. Does the BGA refer to the 19 Commission A every application for every new drug 20 to be approved in Germany? 21 A. Yes. 22 Q. So it is a requirement that 23 the commission review the drug? 24 A. Yes. Page 76 1 Q. And that commission consists 2 of individuals whose sole function is to review 3 the safety and efficacy of a drug? 4 A. Yes, that's right. 5 Q. Are those individuals employed 6 by the BGA? 7 A. No. 8 Q. Are they private citizens? 9 A. They are private citizens not 10 employed by the BGA. And when I say that every 11 drug goes to the commission, that is perhaps not 12 fully true. Every new drug yes, but not every 13 application. If it is just an extension of the 14 application or something, then it does not 15 necessarily go to the commission. 16 MR. SMITH: All right. Off the record 17 for a second. 18 (DISCUSSION OFF THE RECORD.) 19 Q. (BY MR. SMITH) Doctor Weber, 20 we've moved into a different room to try to 21 reduce the background noise. Before we moved, we 22 were discussing the Commission A that is employed 23 by the BGA in connection with their drug approval 24 process there, correct? Page 77 1 A. Yes. 2 Q. Is it medical doctors that 3 comprise the Commission A? 4 A. Yes. 5 Q. Is it exclusively medical 6 doctors? 7 A. Yes. 8 Q. And are those medical doctors 9 that is selected by the BGA for Commission A, do 10 they have some special competence in evaluating 11 drugs and drug safety or in a particular 12 specialty? 13 A. No, they are specialized in 14 the disease -- 15 Q. All right. 16 A. -- what it's talking about. 17 Q. Okay. Is the commission 18 always made up of the same members or will there 19 be a different commission for let's say 20 cardiovascular drugs, a different commission for 21 nervous system drugs and a different commission 22 for other types of drugs? 23 A. No, it is the same commission 24 for every type of drug. Page 78 1 Q. So does that commission have 2 different representatives of different 3 specialties within the commission? 4 A. That is right, yes. 5 Q. And if it's an antibiotic -- 6 A. Uh-huh. 7 Q. -- will those commissioners on 8 Commission A who are specialists in let's say 9 infectious disease and things of that nature, 10 will they be the ones that will take a 11 particularly close look at that particular 12 product? 13 A. Yes, they receive -- one of 14 the specialists will receive a book, a 15 documentation from the BGA in order that he can 16 talk about this particular documentation in more 17 detail. 18 Q. What is that book called that 19 that specialist receives? 20 A. It is called something like 21 Weiss Buch, White Buch or something which 22 contains the most important information of the 23 documentation. 24 Q. What would be -- you called it Page 79 1 Weiss Buch? 2 A. Yes. 3 Q. Would there be an English word -- 4 A. No, I don't know an English 5 word, Weiss Buch, W-E-I -- you don't have it in 6 English -- double S, B-U-C-H. 7 Q. Can you give us an English 8 translation or approximation of what that book 9 would be named? 10 A. No, not about the name -- 11 well, White Book is the real translation. 12 Q. All right. Like the color 13 White Book? 14 A. Yes, like the color. And it 15 contains the summary of the most important 16 elements of the registration dossier. 17 Q. And that is something that is 18 provided to that particular specialist on the 19 commission by the BGA? 20 A. That is right. 21 Q. Now, does the BGA prepare that 22 White Book or does the sponsor of the drug 23 prepare that White Book to be sent to that 24 specialist? Page 80 1 A. That is prepared by the BGA. 2 Q. All right. Does that White 3 Book have some requirements for what needs to be 4 contained within that book? 5 A. Probably, but I'm not aware 6 about this. 7 Q. Is the sponsor of the 8 medication privy to that book or what's in that 9 book? 10 A. No, the sponsor has nothing to 11 do with the book. 12 Q. I understand that the sponsor 13 may not comprise the book, but does the BGA give 14 the sponsor a copy of the book that the -- 15 A. No. 16 Q. -- particular expert is going 17 to get -- 18 A. No. 19 Q. -- so that they'll know what 20 information the commission has? 21 A. No, unfortunately not. 22 Q. You say unfortunately not. 23 A. Yes. We would like to know 24 what they are talking about, yes. Page 81 1 Q. So then that commissioner that 2 receives that White Book discusses the product 3 with the other commissioners? 4 A. Yes. 5 Q. And they're all medical 6 doctors and scientists and they discuss it, the 7 product, on a scientific basis? 8 A. Yes, right. 9 Q. Do they have formal meetings? 10 A. I think they have meetings 11 once a month which are called by the BGA, and 12 they have an agenda. 13 Q. Are there members of the BGA 14 present at that meeting or is that an autonomous 15 meeting where just the commissioners meet? 16 A. No, members of the BGA are 17 present and listen and also make recommendations. 18 Q. Is the sponsor, the 19 pharmaceutical manufacturer, entitled to be there 20 at those meetings? 21 A. No. 22 Q. Is the sponsor, the 23 pharmaceutical manufacturer, prohibited from 24 being at those meetings? Page 82 1 A. He is prohibited, yes. 2 Q. Why is that, sir, do you know? 3 A. No, no. 4 Q. Is it so that there can be an 5 evaluation of the product made without an input 6 from the sponsor? 7 A. That is right. That is a 8 difference to the situation here in the United 9 States, yes. 10 Q. So the BGA wants to keep the 11 sponsor's opinions separate from an independent 12 evaluation by the BGA and the Commission A, is 13 that right? 14 A. That is right, yes. 15 Q. Then what does the commission 16 do, does the commission vote on a particular 17 medication in determining the recommendation or 18 how do they work once they are brought up-to-date 19 on this drug by the particular specialist on the 20 commission? 21 A. I don't know in particular how 22 they operate. I think it is that the BGA 23 reviewer makes recommendations and the commission 24 agrees to the recommendations or do not agree to Page 83 1 the recommendations, and at the same time the 2 Commission A can make recommendations by 3 themselves to the BGA. 4 Q. Can the Commission A issue 5 questions as to further areas of inquiry 6 concerning the safety and efficacy of the drug in 7 order to get better information concerning that 8 product? 9 A. As far as I'm aware, they can 10 do this, yes. 11 Q. And have they done that as far 12 as you know? 13 A. I don't know because we do not 14 know what is going on with the commission. 15 Q. The commission is a body that 16 is kept separate from the manufacturer? 17 A. Yes, that's right. 18 Q. And their analysis of the drug 19 is done independent from the manufacturer? 20 A. That is right. 21 Q. Does the commission do 22 independent clinical testing? 23 A. No, no. 24 Q. Does the commission do any Page 84 1 type of toxicology studies or things of that 2 nature? 3 A. No, no. 4 Q. Does the BGA do independent 5 clinical testing? 6 A. No, they are doing some 7 research testing, but not independent testing in 8 the nature of approval of the drug. 9 Q. But the BGA is just like the 10 United States Food and Drug Administration in 11 that respect -- 12 A. Yes. 13 Q. -- that they don't conduct 14 clinical trials. 15 A. That is right. 16 Q. They rely on the manufacturer 17 of the product -- 18 A. Yes. 19 Q. -- being submitted to conduct 20 the clinical trials, correct? 21 A. That is right. Can I perhaps 22 say when you asked the question can the 23 Commission A members run clinical trials, yes, 24 they run clinical trials, but not particularly in Page 85 1 terms of the application or to clarify something 2 that's in the application. But at the same time, 3 they as clinical experts are also investigators. 4 Q. All right. So they may be 5 because of their scientific expertise individuals 6 who are called upon from time to time by drug 7 manufacturers to conduct clinical trials. 8 A. That is right. 9 Q. But they wouldn't be 10 conducting a clinical trial on a drug under 11 inquiry before the Commission A, would they? 12 A. No. 13 Q. Or for Commission A, would 14 they? 15 A. No, no. 16 Q. Or at the insistence of 17 Commission A, would they? 18 A. No, that's right. 19 Q. In fact wouldn't a 20 commissioner who was involved in the conduct of 21 clinical trials of a particular product, if that 22 product were under the review process by the 23 commission have to abstain from any decision 24 making in connection with that particular Page 86 1 product? 2 A. Not necessarily. He has to 3 indicate that he has done a study with this drug, 4 but then he can -- then the commission may decide 5 whether he has still the right to vote, but he 6 still might be on the commission. 7 Q. But he must disclose to the 8 commission that he's conducted a clinical trial 9 on the product under investigation. 10 A. That is right. 11 Q. And it might be that the 12 commission might not let him vote on the approval 13 process of that particular drug? 14 A. Under certain circumstances, 15 that is right, for example when the Commission A 16 member has also served as an advisor to the 17 company. 18 Q. All right. If he is -- if a 19 commissioner is a company advisor, he absolutely 20 cannot vote, is that right? 21 A. That is right, uh-huh. 22 Q. And the reason for that is 23 Commission A wants impartiality in their review 24 process, correct? Page 87 1 A. Yes, yes. 2 Q. And it is prohibited from any 3 members of any advisory board of a particular 4 pharmaceutical company from being involved in the 5 analysis of whether or not a particular product 6 is safe and efficacious? 7 A. That is right. 8 Q. Because the commission doesn't 9 want to be in a conflicting position. 10 A. Uh-huh. 11 Q. Is that right? 12 A. That is absolutely right. I 13 have to add, however, that these things evolved 14 over time, so they are probably more clear today 15 than they have been ten years ago. 16 Q. How many physically members of 17 the Commission A are there? 18 A. Approximately ten to twenty. 19 Q. And if the -- I think we said 20 if the medicine is an antibiotic -- 21 A. Uh-huh. 22 Q. -- it will probably go to some 23 commission member who is familiar with 24 antibiotics? Page 88 1 A. Yes. 2 Q. If it's an antidepressant, 3 such as fluoxetine hydrochloride -- 4 A. Yes. 5 Q. -- who on the commission will 6 review it? 7 A. For an antidepressant? 8 Q. Yes, sir. 9 A. Professor Benkert is currently 10 a member of the commission for antidepressants. 11 Q. Can you spell his -- 12 A. Benkert is B-E-N-K-E-R-T. 13 Q. B-E-N-K-E-R-T? 14 A. E-R-T, yes. And Professor 15 Moller is his replacement. Professor Moller, M-O -- 16 there's two points on it -- L-L-E-R. 17 Q. What is Professor Benkert's 18 first name? 19 A. I don't know. 20 Q. Is he a psychiatrist? 21 A. Yes, he's a psychiatrist, 22 uh-huh. 23 Q. And Professor Moller? 24 A. He's also a psychiatrist. Page 89 1 Q. How long has Professor Benkert 2 been the psychiatrist responsible on Commission A 3 for antidepressant medications? 4 A. He served as far as I know 5 already as a Commission A member in '84. 6 Q. He was a Commission A member 7 in 1984? 8 A. Yes. 9 Q. Was he involved in the 10 Commission A review of fluoxetine hydrochloride? 11 A. I think he was, yes. 12 Q. Any other psychiatrists on 13 Commission A? 14 A. No, the two are now on the 15 Commission A. In earlier times, perhaps during 16 '84, there was another one, Professor 17 Muller-Oerlinghausen. That's a difficult name. 18 M-U -- there's two points on it -- L-L-E-R, and a 19 hyphen, O-E -- O-E-R-L-I-N-G-H-A-U-S-E-N. 20 Q. All right. Were either 21 Professor Benkert, Professor Mollhauser -- Moller 22 or Professor Oerlinghausen ever members of the 23 Lilly Advisory Committee in any fashion as far as 24 you know? Page 90 1 A. Of the Lilly -- member of the 2 Lilly Advisory Commission? 3 Q. Yes -- advisory board. 4 A. Of the Lilly advisory board, 5 not at this time. We have now Professor 6 Muller-Oerlinghausen on our advisory board, yes. 7 Q. Is he still on Commission A, 8 too? 9 A. No, he is not on Commission A. 10 Q. Was he on Commission A? 11 A. I'm not absolutely sure. I 12 think he was. 13 Q. Was he on Commission A when 14 fluoxetine hydrochloride was approved? 15 A. I think he was. 16 Q. Did he disclose to the 17 commission, do you know, that he was on the Lilly 18 Psychiatric Advisory Board? 19 A. No. As I said, at this time 20 he was not on the Scientific Advisory Board. He 21 is now since one or two years as the Scientific 22 Advisory Board. 23 Q. Who on Commission A was it 24 that received this White paper on fluoxetine Page 91 1 hydrochloride that was responsible for explaining 2 the actions of Prozac to Commission A? 3 A. I actually don't know. 4 Q. Would it have had to have been 5 Professor Benkert? 6 A. Yes, yes, Benkert certainly 7 was involved, however Benkert also has written an 8 expert opinion for us. So for this reason, I 9 think he was not the reporter of the Weiss Buch, 10 probably this went to another one. 11 Q. Who would that other man have 12 been? 13 A. I don't know. It could have 14 been Moller, but I do not know. It could have 15 been Moller or Muller-Oerlinghausen, for example. 16 Q. They were the only three 17 psychiatrists that would have been on the Board 18 during this period of time, weren't they, on the 19 commission? 20 A. As far as I'm aware. Maybe 21 there was another one, but these are the three 22 who I know. 23 Q. Now, can the BGA override the 24 recommendations of Commission A? Page 92 1 A. Yes. 2 Q. Do you know of any instance, 3 Doctor Weber, where the Commission A has rejected 4 the approval of a drug and the BGA has overriden 5 that rejection and has approved the drug? 6 A. No, I don't know. 7 Q. You don't know of any instance 8 where it's happened that the Commission A has 9 rejected a drug but the BGA says in spite of 10 Commission A's rejection, we're going to approve 11 the drug? 12 A. They would probably be very 13 careful to do so, so I'm not aware of such a 14 thing happened. It is more likely that the 15 commission recommended approval and the BGA 16 rejects anyway. 17 Q. Why would that occur? 18 A. The BGA is a very -- well, I 19 would say careful or restrictive institution. 20 Q. All right. Is it your 21 experience, Doctor Weber, that the BGA takes 22 responsibly their duties as the overseer of 23 medications administered to individuals in 24 Germany? Page 93 1 A. Whether they take the 2 responsibility for that, yes. 3 Q. Do they take that 4 responsibility seriously? 5 A. Yes, they take this 6 responsibility seriously, right. 7 Q. Is it your opinion based on 8 being a German medical doctor and an individual 9 concerned with pharmacy in Germany that the BGA 10 does a good job in protecting individuals in 11 Germany from drugs that are unsafe or 12 unefficacious? 13 A. I'm going to say I personally 14 have a lot of respect for the BGA, but there are 15 a lot of discussions in the field whether the BGA 16 does this sufficiently well. We had recently 17 something like a scandal related to blood 18 products which were not safe, and it was unclear 19 whether the BGA has dealt with this sufficiently, 20 for example, and there are other discussions as 21 well. 22 Q. What you're saying is 23 sometimes the BGA comes under fire if there's a 24 product that's approved that later is determined Page 94 1 to be unsafe? 2 A. Yes, that's right. 3 Q. And you're familiar of course 4 that the FDA comes under fire also if they 5 approve a product and it's later determined that 6 that product becomes unsafe? 7 A. It's likely. 8 Q. During your time in the United 9 States, you saw that, didn't you? 10 A. Well, it happens from time to 11 time, but I do not remember a particular case. 12 Q. Do you know that the BGA does 13 as equally good a job in protecting individuals 14 in Germany as the FDA does in protecting 15 individuals in the United States? 16 A. Well, I think the ultimate 17 goal of both institutions is the same, to protect 18 the individuals. They have a little bit 19 different measures, sometimes draw little bit 20 different conclusions. I think that the BGA is a 21 difficult organization in this respect and may 22 raise a number -- they usually raise a number of 23 questions. Altogether, I would say both are good 24 organizations. Page 95 1 Q. All right. Do you find the 2 difficulties with the BGA perceived from your 3 perspective as the medical director of a 4 pharmaceutical company operating in Germany? 5 A. I have sometimes difficulty 6 because they appear in two different respects. 7 Sometimes they appear to raise questions which I 8 don't understand and seem not very logical. And 9 secondly, the difficulty is that you -- it is 10 very difficult to talk to the BGA. You can talk 11 to the FDA, you can call the FDA, talk to them, 12 what is really the issue, try to understand what 13 they are trying to ask, but in Germany, this is 14 very difficult. 15 Q. The BGA sort of insulates 16 themselves from the pharmaceutical manufacturer 17 in Germany, don't they? 18 A. Much more than in the United 19 States, yes. 20 Q. There's a lot more free 21 exchange between the FDA and the pharmaceutical 22 industry in the United States than there is 23 between the BGA and the pharmaceutical industry 24 in Germany? Page 96 1 A. Yes, that is right. 2 Q. And there's a lot more 3 questions raised in Germany than there is in the 4 United States, isn't there? 5 A. That depends. But usually the 6 BGA has a lot of questions, that is right. 7 Q. Isn't it true, Doctor Weber, 8 that the BGA, even though they may be raising 9 questions, are generally raising legitimate 10 questions concerning the safety and efficacy of 11 products under the review process? 12 A. Well, I would say we take it 13 serious and we think that there are very valid 14 questions, but there are also questions which in 15 our opinion sometimes do not have a background. 16 Q. Well, you don't consider -- 17 let's just face it, Doctor Weber, you don't 18 consider the questions that the BGA raised in 19 connection with fluoxetine and suicidality and 20 violent aggressive behavior as being stupid 21 questions, do you? 22 MR. MYERS: I object to the form. Go 23 ahead and answer, Doctor. 24 A. No, I would not call them Page 97 1 stupid questions, no. 2 Q. They were in fact legitimate 3 questions to be raised, weren't they? 4 MR. MYERS: Same objection. Go ahead. 5 A. I do not understand exactly 6 the word legitimate. Means something -- 7 Q. They had a scientific basis 8 for being raised, whether right or wrong there 9 was a scientific reason to raise those issues, 10 wasn't there? 11 A. There was a reason to raise 12 these issues, yes. 13 Q. And that reason was based on 14 scientific issues, wasn't it? 15 A. It was based upon data, yes. 16 Q. Which was scientific, wasn't 17 it? 18 A. Scientific, yes. 19 Q. It was data that had been 20 submitted by Lilly, wasn't it? 21 A. Excuse me? 22 Q. The BGA data, the data that 23 the BGA was reviewing was submitted to the BGA by 24 Lilly, wasn't it? Page 98 1 A. Yes, yes, yes. 2 Q. You didn't consider the 3 questions on suicide and violent aggressive 4 behavior in connection with Prozac, Fluctin, to 5 be trivial, did you? 6 A. No. 7 MR. MYERS: Object to the form. Go 8 ahead. 9 A. No, they were not trivial 10 questions. 11 Q. When you asked Professor 12 Benkert his expert opinion on the suicide issue, 13 was he a member of Commission A? 14 MR. MYERS: I object to the form. 15 A. Yes, he was a member of the 16 Commission A, as far as I know, yes. 17 Q. How was it then that Lilly was 18 able to employ Professor Benkert to be an expert 19 on this suicide issue when he was a member of the 20 commission reviewing the application of Prozac in 21 Germany? 22 A. Well -- 23 MR. MYERS: Let me object to the form. 24 I don't know that he's testified to that, as to Page 99 1 what the subject matter was that the professor 2 was an expert on. You're assuming it was 3 suicide. 4 A. I just wanted to say we did 5 not ask him to particular comment on suicidality, 6 he was asked to give his opinion about the 7 efficacy of the drug. 8 Q. Is it your testimony that he 9 didn't mention anything about the issue of Prozac 10 and suicide in his opinion? 11 A. We did not ask him especially 12 to give comments about suicidality. I do not 13 remember whether he not made the remark about 14 suicidality anyway because it -- it is in some 15 way related to the benefit/risk situation of 16 Fluctin, so I think he made a comment about it 17 but he was not particularly asked to address 18 suicidality. 19 Q. How was it -- my question was, 20 how was it that he was employed as an expert to 21 render any opinion on fluoxetine hydrochloride 22 when he was a member of Commission A? 23 A. You can do this any time of 24 course, but then he has to disclose that he is Page 100 1 doing work, giving expert opinion for the 2 company. We employed him for a particular reason 3 because he was also one of our investigators. 4 Q. All right. Do you know 5 whether or not he disclosed that to Commission A? 6 A. I do not know what he 7 disclosed to the BGA. 8 Q. Did you ever talk to Professor 9 Straeter, the lawyer, about the appropriateness 10 of doing this? 11 MR. MYERS: Well, before he answers, 12 let me instruct you, Doctor Weber, you don't have 13 to disclose the substance of anything you 14 discussed with Mr. Straeter, that's 15 attorney-client privilege, he's a lawyer, and a 16 lawyer for Lilly in Germany. You can answer the 17 question yes or no. 18 A. No. 19 Q. Do you know Professor 20 Straeter? 21 A. Mr. Straeter is a lawyer, yes, 22 I know him very well. 23 Q. You know him very well. 24 A. Uh-huh. Page 101 1 Q. Now he was a lawyer for the 2 BGA, wasn't he? 3 A. That is right. 4 Q. Was he a lawyer for Lilly at 5 the same time he was a lawyer for the BGA? 6 A. No. 7 Q. All right. When did he cease 8 to become a lawyer for the BGA? 9 A. That was around '84, I would 10 guess, approximately '84. 11 Q. So that was while fluoxetine 12 hydrochloride, Prozac, Fluctin, was still in the 13 approval process before the BGA, was it not? 14 A. I think he discontinued from 15 the BGA before the fluoxetine application. 16 Q. All right. And then when did 17 Lilly hire him, in '84? 18 A. Yes, I think in '84, yes. 19 Q. And he was hired specifically 20 to represent Lilly in getting fluoxetine 21 hydrochloride approved in Germany? 22 A. No, he was hired as legal 23 consultant. 24 Q. Yes, for the approval of Page 102 1 Prozac in Germany. 2 A. That was one of his jobs, yes. 3 Q. Did he come to work full time 4 for Lilly as a legal consultant? 5 A. No, no, part time. So we have 6 meetings with him every two months and otherwise 7 called him when we have something to discuss with 8 him. 9 Q. Why would -- did you select 10 him as your lawyer? 11 A. As I said, I respect the BGA 12 very much and especially I had to deal with Mr. 13 Straeter when he was a member of the BGA in a 14 different case, not on Fluctin, and he impressed 15 me very much. And when he left the BGA, I asked -- 16 and became a free lawyer, I asked him whether he 17 would consult for us. 18 Q. And so you were the one who 19 directly approached him to hire him as the Lilly 20 lawyer? 21 A. That is right, yes. 22 Q. Were you and he friends at the 23 time? 24 A. No. Page 103 1 Q. Have you since become friends? 2 A. I would not say friends, but 3 we respect each other very much and talk about 4 general issues. 5 Q. As friendly as anybody can 6 become with a lawyer? 7 A. Yes, right. 8 Q. Why did Professor or Mr. 9 Straeter leave the BGA, do you know? 10 A. I did not talk about this 11 particular issue, but I mean the opportunities 12 for him in the free -- practicing as a free 13 lawyer are much better than at the BGA where he 14 is paid by the government. 15 Q. Make more money? 16 A. I think that was certainly one 17 of the reasons, yes. 18 Q. Do you know whether or not Mr. 19 Straeter does anything but do legal consultant 20 work for pharmaceutical firms before the BGA? 21 A. No, he is a legal consultant, 22 that is what he's doing. 23 Q. Just for the pharmaceutical 24 industry? Page 104 1 A. No, he's also legal consultant 2 for physicians, dealing -- about negotiations of 3 their salary and those kinds of things. 4 Q. All right. With hospitals or 5 with the BGA? 6 A. No, with -- between -- well, 7 the way physicians are paid is that they have to 8 report to a certain commission, and between this 9 commission and the physicians, something -- a 10 legal consultant is necessary. 11 (PLAINTIFFS' EXHIBIT NO. 1 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Exhibit 1 is a document dated 15 June 26, 1984, is it not? 16 A. Yes. 17 Q. And it's directed to Ms. 18 Ashbrook, Doctor Hardison and Doctor Stark in 19 Indianapolis, correct? 20 A. Yes. 21 Q. And it is signed by -- or 22 appears to be authored by yourself and Doctor 23 Schenk, is that right? 24 A. Yes, that's right. Page 105 1 Q. Is this a document that you 2 reviewed in preparation for your deposition, 3 Doctor Weber? 4 A. Yes. 5 Q. And did you author this 6 document? 7 A. Did I? 8 Q. Did you author this document, 9 did you write this document? 10 A. It was certainly written by 11 Johanna Schenk, and I looked at it before it was 12 sent, yes. 13 Q. You approved the contents of 14 the document? 15 A. Yes. 16 Q. Was Ms. Schenk or Doctor 17 Schenk a physician under -- 18 A. Yes. 19 Q. -- your direction? 20 A. That is right. 21 Q. And you were responsible for 22 her actions? 23 A. Yes. 24 Q. Did you feel that Doctor Page 106 1 Schenk was competent? 2 A. Yes, uh-huh. She was not a 3 psychiatrist, but very competent in drug 4 development, yes. 5 Q. You respected her judgment as 6 a scientist? 7 A. Yes. 8 Q. Were there any psychiatrists 9 employed by Lilly in Germany in June, 1984? 10 A. There was no psychiatrists 11 employed. 12 Q. Do you recall this document 13 being prepared and sent? 14 A. Well -- yes. 15 (A SHORT RECESS WAS TAKEN.) 16 Q. (BY MR. SMITH) Doctor Weber, 17 Exhibit 1 is dated June 26, 1984. You were the 18 medical director for Eli Lilly and Company in 19 Germany at the time, is that right? 20 A. Yes. 21 Q. The first paragraph says, this 22 is to confirm which additional data had been 23 identified to be essential during our discussions 24 at the BGA June 15, 1984, correct? Page 107 1 A. Yes. 2 Q. It talks about discussions at 3 the BGA. 4 A. Uh-huh. 5 Q. When were there discussions -- 6 were there physically discussions at the BGA? 7 A. To tell you the truth, I do 8 not remember this, I was not part of this 9 discussion. But obviously there were discussions 10 of members of my group together with the BGA. 11 Q. Do you think that Doctor 12 Schenk would have been -- 13 A. Yes. 14 Q. -- present? 15 A. Yes, probably, yes. 16 Q. I thought that we had 17 developed earlier that there couldn't be the 18 exchange and the interchange between the 19 pharmaceutical industry and the BGA like there 20 could be with the FDA? 21 A. Uh-huh. 22 Q. Is that correct? 23 A. That is right. Nevertheless, 24 on particular occasions it may happen, more or Page 108 1 less on an exceptional basis, not on a regular 2 basis, yes. 3 Q. So this would have been an 4 exception that you all would be at the BGA? 5 A. That is tough to get such a 6 meeting, yes. 7 Q. Do you recall the 8 circumstances of this meeting, Doctor Weber? 9 A. Only in that way that we 10 wanted to discuss with the BGA because we did not 11 understand some of their questions and wanted to 12 get clarification what they actually mean with 13 the questions. 14 Q. So the BGA allowed Lilly to 15 come to them and discuss with them specific 16 items? 17 A. Yes. 18 Q. Is that right? 19 A. Yes, but I do not remember how 20 in this specific case we have set this up. 21 Q. Who would have set that up? 22 A. I guess Johanna Schenk. 23 Q. Would Mister Bouchy might have 24 set that up? He was the -- Page 109 1 A. Very unlikely, very unlikely. 2 Q. It would have been somebody in 3 the medical component, is that right? 4 A. Yes. 5 Q. And you didn't do it, so you 6 think it was Doctor Schenk? 7 A. Yes. 8 Q. Would she have been your 9 second in command at that time? 10 A. Would she have been the -- 11 Q. Your second in command at that 12 time. Do you understand that term? 13 A. Well, in the area of Fluctin, 14 yes. 15 Q. So she was -- well, was she -- 16 you were the medical director, correct? 17 A. Right. 18 Q. So you were responsible for 19 all Lilly products, correct? 20 A. For a variety of things, yes. 21 Q. Was Doctor Schenk specifically 22 responsible for fluoxetine hydrochloride? 23 A. That is right. 24 Q. All right. Her work was such Page 110 1 that she had the direct responsibility for the 2 work on fluoxetine hydrochloride. 3 A. That is right, at this point 4 in time, yes. 5 Q. So it was natural that she 6 appeared at the BGA. 7 A. Right, uh-huh. 8 Q. Do you recall her physically 9 going to the BGA? 10 A. No, I do not recall it. 11 Q. Do you recall her coming to 12 you and reporting to you the results of the 13 meeting? 14 A. I remember some of the 15 elements of what we discussed, but I do not 16 recall actually how it happened, how he picked -- 17 how she picked the information up, some perhaps 18 also by telephone discussions. So I do not 19 recall her coming back from the BGA and report to 20 me. 21 Q. Would there have been any 22 members of Commission A at this meeting? 23 A. Certainly not, certainly not. 24 Q. Why? Page 111 1 A. There are never Commission A 2 members at the BGA when you have a meeting with 3 the BGA. 4 Q. Why is that, is it prohibited? 5 A. It is not prohibited, but it 6 would make it even more difficult to get a 7 meeting with the BGA. 8 Q. Why? 9 A. Well, you have to ask the 10 Commission A member, whether he would like to 11 come or -- let's say first you have to ask the 12 BGA whether they would allow that the Commission 13 A member also comes to such a meeting, and we 14 have never done this. 15 Q. And you and Doctor Schenk list 16 a number of concerns that were voiced to you at 17 the meeting at the BGA. 18 A. Uh-huh. 19 Q. Is that right? 20 A. Uh-huh. 21 Q. You have to say yes or no 22 here. 23 A. Excuse me, yes. 24 Q. Did the BGA have a Page 112 1 psychiatrist or somebody specially trained in 2 antidepressant or psychotropic medications 3 reviewing Prozac? 4 A. I know the reviewer of the 5 BGA, I'm not sure that he is really a 6 psychiatrist. 7 Q. Who is -- who was the 8 reviewer? 9 A. The reviewer was Doctor 10 Karkos, K-A-R-K-O-S. 11 Q. And you don't know whether 12 he's a psychiatrist or not? 13 A. I think he is a specialist in 14 the CNS area, but I don't know whether he's a 15 psychiatrist. Today he's the reviewer for 16 neurology. 17 Q. So he may be a neurologist? 18 A. He may be a neurologist, yes. 19 Q. The second point there says 20 the BGA stated that there is a disagreement 21 between patient's and doctor's judgment of 22 efficacy. Since in their opinion the patient's 23 impression is more important, we have to 24 demonstrate correlation between SCL 58 and HAMD Page 113 1 and CGI and PGI respectively, paren, perhaps by 2 graphs, close paren, correct? 3 A. Uh-huh. 4 Q. Is that a yes? Obviously it 5 appears that the BGA has seen some data in order 6 to make this comment. 7 A. Yes. 8 Q. And that data that they've 9 seen has to be the data that was submitted by 10 Lilly, doesn't it? 11 A. Yes, they are referring to 12 Lilly data certainly. 13 Q. And that Lilly data reflected 14 some -- apparently some difference in doctor's 15 judgment concerning efficacy of Prozac and 16 patient's judgment concerning efficacy of Prozac, 17 correct? 18 A. Yes. 19 Q. And the BGA is saying there, 20 we feel that the patient's impression concerning 21 the efficacy of Prozac is more important than 22 that of the investigator's, correct? 23 A. That is what they are saying, 24 yes. Page 114 1 Q. Item seven on page two 2 mentions the BGA explained their reservations 3 regarding CNS suicide effects, right? 4 A. Yes. 5 Q. What would be CNS side 6 effects? 7 A. Anxiety, nervousness, 8 psychosis, such kinds of things. 9 Q. The paragraph goes on to 10 explain, there have been a few patients 11 complaining of psychosis and hallucinations. 12 A. Uh-huh, yes. 13 Q. It says please provide us with 14 detailed report whether those patients suffered 15 from psychotic depression, whether the 16 hallucinations developed during treatment or have 17 perhaps been present already at start of 18 treatment or whether those events may indeed be 19 interpreted by aggravation of disease, end quote, 20 correct? 21 A. Yes. 22 Q. Were you aware at the time of 23 potential CNS side effects that had occurred with 24 Prozac? Page 115 1 A. Certainly the CNS events 2 happened frequently. There's a difficulty 3 certainly to figure out whether it is the cause 4 of the disease or whether it is the drug which is 5 given. 6 Q. At this time or before this -- 7 A. Yes. 8 Q. -- did you know that there was 9 some concern that Prozac itself was producing 10 some CNS side effects? 11 A. Before this? 12 Q. Before this date of June 26, 13 1984. 14 A. I think the BGA has already 15 expressed their concerns in the previous letter. 16 Q. And their concern was that it 17 was producing CNS side effects. 18 A. That is correct. 19 Q. Item ten states comparative 20 use of concomitantly taken hypnotics and 21 benzodiazepines in agitated/retarded fluoxetine 22 patients versus agitated/retarded patients on 23 comparators. Reason: The BGA suspects 24 fluoxetine to be a stimulating/activating drug Page 116 1 (side effect profile, suicides, suicide 2 attempts), end quote, correct? 3 A. Yes. 4 Q. Before this, did you know that 5 the BGA had suspected that Prozac was an 6 activating drug? 7 A. Again, that was stated as far 8 as I remember in the letter of concerns which we 9 received from the BGA. I do not remember whether 10 it was the first or the second letter from the 11 BGA. 12 Q. It was contained in both 13 letters of concerns, wasn't it, Doctor Weber? 14 A. I'm not sure, but it was 15 certainly in one of the letters, yes. But 16 suicidality was in both letters, you're right. 17 Whether activating was in both letters, I don't 18 know. 19 Q. Again, this is the BGA's view 20 of problems associated with the drug based on 21 review of Lilly data, isn't that correct? 22 A. Yes, that is correct. 23 Q. Would the BGA -- do you know 24 whether or not the BGA's concerns at this time Page 117 1 were based on consultation with Commission A? 2 A. It's unlikely that this was 3 based on consultation with BGA because the 4 consultation with Commission A -- the 5 consultation with Commission A usually occurs 6 later, at a later point. 7 Q. This would have been then 8 something that Doctor Karkos -- 9 A. Karkos, yes. 10 Q. -- would have been raising -- 11 A. Yes. 12 Q. -- in his review of the Lilly 13 data? 14 A. Yes, yes. 15 Q. And he suspected it to be a 16 stimulating drug? 17 A. Yes. 18 Q. Item twelve indicates that 19 based on the Lilly data, quote, the BGA stated 20 that due to the accumulation of fluoxetine, we 21 should consider to recommend a lower maintenance 22 dose after having achieved a certain relief of 23 acute symptoms. They advised to give clear 24 instructions concerning dose adjustment with Page 118 1 time, correct? 2 A. Yes. 3 Q. That was never done, was it? 4 A. Clear instructions concerning 5 dose adjustment with time, no, we did not feel 6 that this was necessary. 7 Q. Item fourteen indicates, 8 quote, based on the Lilly data, quote, as we 9 already explained by our telex to Doctor Zerbe of 10 June 8, '84, we need a careful analysis of 11 suicides and suicide attempts, patient by 12 patient, symptomatology, severity upon entry into 13 the study, and week by week until the event 14 occurred, dose of fluoxetine, side effects, et 15 cetera. This is a very serious issue in the 16 opinion of the BGA. It might well be that we 17 will have to recommend concomitant tranquilizer 18 intake for the first two or three weeks in the 19 package literature, end quote, correct? 20 A. Yes. 21 Q. That's in fact what occurred, 22 isn't it? 23 A. I'm sorry, I did not hear. 24 Q. The package insert on Fluctin -- Page 119 1 A. Yes. 2 Q. -- requires that there is a 3 recommendation of concomitant tranquilizer intake 4 at the outset of Prozac therapy in certain 5 patients. 6 A. Yes. 7 MR. MYERS: Hold on. Let me object to 8 the form. Go ahead and answer. 9 A. But not regularly. But there 10 may be patients where this might be reasonable, 11 yes. 12 Q. So the answer is in certain 13 patients, that is certain patients who present a 14 risk of suicide or certain patients who are 15 excitable, that there should be concomitant -- 16 that the physician should consider use of 17 tranquilizers during initial stages of Prozac 18 therapy? 19 A. The package labeling says 20 something of this nature, that either in patients 21 at risk of suicide, the patient should be 22 carefully supervised or sedative might be given. 23 Q. And in cases of suffering from 24 excitability? Page 120 1 A. Suffered from excitability, 2 no. In patients who are nervous or who have 3 insomnia, they may also require sedative. I 4 think that is what the labeling says. 5 (PLAINTIFFS' EXHIBIT NO. 2 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Doctor Weber, can you identify 9 Exhibit 2? 10 A. Yes. 11 Q. I can't. Why can't I? 12 A. It is in German. 13 Q. All right. Is this the German 14 package insert or is this the German prescribing 15 information for professionals? 16 A. No, that is the German package 17 insert. 18 Q. Is this what the patient gets 19 or is this what the doctor gets? 20 A. This is -- the patient. 21 Q. Describe or read for us what 22 the German package insert says concerning use of 23 tranquilizers and risk of suicide. 24 A. Well, that is mentioned under Page 121 1 patients at risk. And patients at risk, it 2 starts with a patient at risk or such with -- at 3 risk of suicide. Fluctin -- 4 Q. That's Prozac, isn't it? 5 A. That is Prozac. Is not in 6 general sedating, therefore the patient should be 7 supervised carefully until the antidepressant 8 effect of fluoxetine is fully employed. The 9 additional medication of sedative product may be 10 required. This also might be necessary in case 11 of sleep disorders or agitation. 12 Q. Is that for -- is that what 13 doctors get or is that what patients get? That's 14 information for doctors, isn't it? 15 A. That is in -- that is more 16 information for doctors, that's right. But the 17 rule in Germany is that we have professional 18 information and patient information, and the 19 patient information needs to be in content same 20 as the professional information, therefore this 21 language is included in the patient information 22 as well. 23 Q. And all of this language is 24 contained under risk patients, isn't it? Page 122 1 A. This language is related to 2 risk patients, yes. 3 Q. And it specifically talks 4 about patients who are a risk of suicide, doesn't 5 it? 6 A. Yes. 7 Q. And what does it say about 8 those risks? Read it for us since we don't read 9 in German and you do. 10 A. So I should read it again? 11 Q. Please. 12 A. Fluctin or Prozac is not a 13 general sedating on the central nervous system. 14 Therefore the patient for his own safety should 15 be closely supervised until the antidepressant 16 efficacy of Fluctin is employed or starts to 17 work. The additional use of the sedative 18 compound can be required. 19 Q. In suicidal patients? 20 A. In patients at risk of 21 suicides. 22 Q. All right. 23 A. This may also be necessary in 24 cases of sleep disturbances or agitation. Page 123 1 Q. That language then in Exhibit 2 2 is the result of findings back as early as 1984 3 or thoughts back as early as 1984, that it may 4 well be that we have to recommend concomitant 5 tranquilizer intake for the first two or three 6 weeks in package literature, correct? 7 A. If you phrase the question 8 this way, I would say no, it is not. Because the 9 difficulty at this point of time was the 10 suicidality an issue, yes or no. And if it would 11 have been an issue, we would not have got the 12 drug approved. However, in Germany there is a 13 certain tradition to talk about suicidality 14 anyway because that is an inherent risk of 15 depression. And so that is the language which is 16 used as we learned with time, also in other 17 labelings of antidepressants. 18 Q. Are you -- is it your 19 testimony, Doctor Weber, that in every 20 antidepressant marketed in Germany, that there is 21 a requirement in package labeling that that 22 antidepressant have concomitant sedative use for 23 the first two or three weeks of treatment? 24 A. No, I don't. Page 124 1 MR. MYERS: Hold on. Let me object to 2 the form of the question. Go ahead and answer. 3 A. I did not say this, I said 4 there is a statement probably about suicidality 5 and I cannot tell you whether it is in every 6 labeling because things evolve over time and some 7 of the antidepressants have been approved ten, 8 twenty years ago before we even had reasonable 9 drug law. But in recent science, this recent 10 antidepressant, such a statement about 11 suicidality is included. Rather it is included 12 that a sedative might be necessary, that can be 13 different because some antidepressants are 14 sedative by themselves, they have the side effect 15 of sedation. 16 Q. All right. Prozac doesn't 17 have that side effect, does it? 18 A. Prozac in general does not 19 have this side effect, yes. 20 Q. And in general Prozac is a 21 stimulating -- 22 A. No. 23 Q. -- antidepressant, isn't it? 24 A. No, no, no. Page 125 1 Q. On what scientific basis do 2 you disagree with that proposition? 3 A. Prozac is in some patients 4 sedating and is in some patients activating, but 5 in the majority of patients it is neither the one 6 nor the other. 7 Q. Well, do you know, sir, that 8 in placebo-controlled trials that Prozac was 9 activating in more instances than placebo? 10 A. Yes, and it was sedating in 11 more instances as placebo. 12 Q. And it was activating in more 13 instances than it was sedating too, wasn't it, 14 Doctor Weber? 15 A. I'm not sure about that. 16 Q. You're not sure about that. 17 A. Uh-uh. 18 Q. Well, the figures are 19 thirty-eight percent activating and twelve 20 percent sedating. 21 A. Well, then -- 22 MR. MYERS: Object to the form. 23 Q. Did you know that? 24 A. I think there is a Page 126 1 publication, and as far as I remember the boss, 2 the boss are a little bit higher on the 3 activating side. Whether this was a statistical 4 relevant difference, I don't know, but there is a 5 tendency, that is right. 6 Q. It's more likely to be 7 activating than sedating, isn't it, Doctor Weber? 8 A. You can't predict on any 9 particular patient. 10 Q. Based on what expertise? 11 A. Well, on several expertise, 12 because sedation and depression may occur in the 13 course of the disease anyway, and the drug may 14 act or may be efficacious in individual patients 15 or it may not, and the patient may develop 16 sedating features or stimulating features. 17 Depression is not a static disease, it has a lot 18 of variations during the course of the disease. 19 Q. Is this based on your 20 observations, Doctor Weber? 21 A. It is not based on my 22 observations because I did not treat depressive 23 patients, but that is as I learned during my 24 medical -- at medical school and later school Page 127 1 publications because I had to go a little bit 2 deeper in this. 3 Q. Do you have an opinion whether 4 or not the German package insert is incorrect in 5 its recommendations concerning Prozac usage in 6 patients who are at risk of suicide? 7 A. No, I think the German 8 labeling is correct. 9 MR. SMITH: Let's take a lunch break. 10 (A LUNCH RECESS WAS TAKEN.) 11 Q. (BY MR. SMITH) Doctor Weber, 12 do you disagree that -- with the BGA as stated in 13 Exhibit 1 that Prozac is an activating 14 antidepressant? 15 A. I disagree with that, yes. 16 Q. You disagree with that? 17 A. Yes. 18 Q. They do make that statement, 19 though, do they not? 20 A. The BGA has made the 21 statement, yes. 22 Q. Would you agree that in 23 looking at side effects and the side effect 24 profile of Prozac, that there are more instances Page 128 1 of activating type side effects than sedating 2 side effects? 3 A. When you call anxiety and 4 agitation and nervousness being related to 5 activation, then you are right. I'm not sure 6 whether this really is the same because agitation 7 is more psychomotoric while activation is more 8 psychic. There's a difference. 9 Q. But as far as the side effect 10 profile, Prozac is more likely to have activating 11 type side effects than sedating side effects, 12 correct? 13 A. No, I think in this way stated 14 it is not correct. 15 Q. How was it stated incorrectly? 16 A. I think there's a difference 17 between activation and agitation, nervousness, 18 insomnia and those kinds of things. But if you 19 put this all together and say that would be 20 features of activation, then you are right. 21 Q. All right. These are all side 22 effects that are side effects that are seen with 23 stimulants also, are they not? 24 A. Side effects of stimulants can Page 129 1 be of this nature. 2 Q. Such as agitation? 3 A. Yes. 4 Q. Nervousness? 5 A. Yes. 6 Q. Irritability? 7 A. What was that? 8 Q. Irritability? 9 A. Irritability, I think so, yes. 10 Q. Excessive sweating? 11 A. Yes. 12 Q. Tremors? 13 A. Yes. 14 Q. These are all side effects of 15 stimulating or stimulant type drugs? 16 A. Yes, uh-huh. 17 Q. Was there in your observation 18 of the differences or distinctions between 19 Commission A and the BGA, is there some animosity 20 or ill will between those two groups? 21 A. There are some disagreements 22 between the two groups, that is right. 23 Q. What is the principle area of 24 disagreement? Page 130 1 A. It depends also a little bit 2 upon the reviewers of the BGA. I think that a 3 particular reviewer in the CNS field is regarded 4 as being difficult, so there are frequently, as I 5 have heard, disagreements between this reviewer 6 and the Commission A. 7 Q. Well, would that be the 8 reviewer -- 9 A. Karkos. 10 Q. -- Karkos in connection with 11 Prozac? 12 A. Yes. 13 Q. And he was more stringent in 14 connection with the approval process than the 15 commission was? 16 A. Yes, you can call it 17 stringent, he's certainly stringent, but he 18 raises also some questions which were felt by us 19 unreasonable and as I've heard sometimes 20 Commission A members feel it's the same way. 21 Q. Does anything specifically 22 come to mind in connection with Prozac where 23 there was a disagreement between the BGA and 24 Commission A? Page 131 1 A. Not that I'm aware of. So 2 obviously the Commission A followed the BGA in 3 this respect. 4 Q. If the BGA issues a medical 5 comment, is that based on input from the 6 commission, Commission A? 7 A. If they issue a medical 8 comment? 9 Q. Yes. 10 A. You mean to the company? 11 Q. Yes. 12 A. That can be influenced by the 13 Commission A, yes, but it has not to be -- not 14 necessarily. 15 (PLAINTIFFS' EXHIBIT NO. 3 WAS 16 MARKED FOR IDENTIFICATION AND 17 RECEIVED IN EVIDENCE.). 18 Q. Look at Exhibit 3. Exhibit 3 19 is a document dated May 25, 1984 and apparently 20 is a cover letter plus a document entitled 21 comment on the clinical documentation, is it not? 22 A. Yes. 23 Q. And it's signed by B. Von 24 Keitz in Bad Homburg, is that correct? Page 132 1 A. Yes. 2 Q. Who is she? 3 A. She is a regulatory person of 4 Eli Lilly in Bad Homburg. 5 Q. The document is addressed to 6 several individuals, but you're not mentioned on 7 this list, are you? 8 A. No, they are addressed to 9 individuals in Indianapolis and Erl Wood. 10 Q. You, however, are familiar 11 with the contents -- the comment on the clinical 12 documentation, are you not? 13 A. Yes, I'm very familiar with 14 it. 15 Q. She didn't need to send you 16 this because you probably had it at the time, 17 right? 18 A. I had it in German, yes. 19 Q. And you probably asked her to 20 send this to these gentlemen? 21 A. That is right. 22 Q. The letter, the transmittal 23 letter from Ms. Von Keitz says yesterday we 24 unofficially received a copy of the medical Page 133 1 comment on our fluoxetine application, a 2 translation is attached, correct? 3 A. Yes. 4 Q. How did you unofficially 5 receive this document? 6 A. Unofficially means that we 7 have received it by fax in advance. The official 8 date of receipt is when we receive it by mail. 9 Q. All right. Who faxed it to 10 you? 11 A. A member of the BGA. 12 Q. Is this something out of the 13 ordinary or is this an ordinary procedure? 14 A. No, that can happen during the 15 course of investigations through the BGA. We 16 sometimes call the BGA and ask what is the status 17 of our application, and then it happens that they 18 tell us where it is and in this case, obviously 19 this thing was written already and then they 20 promised to send it by fax in advance, which can 21 happen from time to time. 22 Q. But your recollection is is 23 that it was received by fax? 24 A. Yes, uh-huh. Page 134 1 Q. Now, it says this is a medical 2 comment, does it not? 3 A. Yes, it is a medical comment, 4 that is right. 5 Q. Does that mean that the BGA 6 has received input from the Commission A? 7 A. Very unlikely at this time. 8 Q. Is the BGA making their own 9 medical analysis? 10 A. Yes, because they have a 11 medical reviewer. 12 Q. And this would have been made 13 by the medical reviewer, you think? 14 A. That would most likely be made 15 by Doctor Karkos, yes. 16 Q. It's not signed. 17 A. It is not signed. And also 18 the official letter which we then probably have 19 received some days later is usually not signed by 20 the medical reviewer, it is signed by a 21 bureaucratic person of the BGA. 22 Q. But this reflects the medical 23 opinion of the BGA. 24 A. That is true, yes. Page 135 1 Q. This is their scientific 2 analysis of the application. 3 A. That is right. 4 Q. And this is their analysis of 5 your application based on data submitted by 6 Lilly. 7 A. That is correct. 8 Q. The medical personnel at the 9 BGA didn't go out and conduct any independent 10 clinical trials. 11 A. I do not know it, but it is 12 unlikely. 13 Q. Would this medical comment be 14 transmitted to the Commission A, would they be 15 aware of its contents? 16 A. Yes, they will be aware of 17 this -- that will be part of the so-called Weiss 18 Buch, yes. 19 Q. The last paragraph of the 20 medical comment -- I'm sorry, the last paragraph 21 of the first page of the medical comment -- 22 A. Uh-huh. 23 Q. -- says, quote, of the 24 forty-six attached study protocols, in Page 136 1 twenty-five the note is to be found that these 2 studies are not completed. Each double-blind 3 study is preceded by a one-week placebo wash-out 4 period. As statements on the medications, which 5 were used in the pretreatments of the depression, 6 are missing, the question occurs, if firstly this 7 period was not too short and on the other hand, 8 if a carry-over effect of those drugs has not 9 influenced the result of the first examination 10 before the beginning of the studies, end quote, 11 correct? 12 A. Yes. 13 Q. That's a critical comment, is 14 it not? 15 A. No, that is not a critical 16 comment, for several reasons. At the time of an 17 application, several studies may go on which are 18 not completed. We make the application when we 19 feel there is enough data to substantiate an 20 approval, and we inform of course about all 21 studies which are going on because this is our 22 application to do so. In terms of the carry-over 23 effect, I think a one week wash-out is a well 24 accepted wash-out period, if you had difficulties Page 137 1 to understand this particular question. 2 Q. Turn with me to the top first 3 paragraph on page three. It says the frequency 4 of side effects was very high, partly more than 5 ninety percent, and the side effects resulted 6 early in each study in dropouts. The frequency 7 of side effects depended on the dose, the age and 8 the duration of therapy. Proceeding -- deciding 9 for the clinical significance of the side effects 10 is not only the frequency of their occurrence, 11 but also their severity, end quote, correct? 12 MR. MYERS: Let me object to the form. 13 You misread one, I think, critical word. 14 MR. SMITH: Okay. Would you point out 15 that for me? 16 MR. MYERS: You said early, and the 17 line says nearly in the second line. You used 18 the word early. 19 MR. SMITH: That's where the stamp is. 20 MR. MYERS: It's not on this one. 21 Q. Let me read it again, Doctor 22 Weber, so I can make sure we get this correct. 23 It says, the frequency of side effects was very 24 high, partly more than ninety percent, and the Page 138 1 side effects resulted nearly in each study in 2 dropouts. The frequency of side effects depended 3 on the dose, the age and the duration of therapy. 4 Deciding for the clinical significance of side 5 effects is not only the frequency of the 6 occurrence, but also their severity, end quote. 7 Did I read it correctly? 8 A. Yes. 9 Q. They found then that side 10 effects was very high, correct? 11 A. Yes. 12 Q. That the side effects depended 13 on the dose given, correct? 14 A. Yes. 15 Q. The duration of therapy, 16 correct? 17 A. Yes. 18 Q. And the age of the patient. 19 A. Yes. 20 Q. This is clinically 21 significant, not only because they occurred at 22 such a frequency, but also because of their 23 severity, correct? 24 A. That is an interpretation, Page 139 1 yes. 2 Q. If you go down then to the 3 fifth paragraph, it says in 15 - 20% percent of 4 cases, side effects occur which involve the 5 central nervous system. As most of them resemble 6 the clinical picture of the underlying disease, 7 even from theoretical reasons, one has to expect 8 an intensification and not an improvement of 9 symptoms, end quote, correct? 10 A. Yes. 11 Q. They're saying there in effect -- 12 that's a little hard to read in English -- but 13 that there's more side effects of a CNS variety 14 than you would even expect in depressed patients, 15 aren't they? 16 A. No, no, they say that they 17 occur at a rate of fifteen to twenty percent. 18 Q. Which is more than you would 19 expect? 20 A. I don't know. 21 Q. It's more than they expected. 22 A. They do not say it here. That 23 is an interpretation. Obviously fifteen to 24 twenty percent is too high for them, I would read Page 140 1 it this way. 2 Q. They are critical of that, are 3 they not? 4 A. They are critical of that, 5 yes. 6 Q. The next paragraph says, 7 during the treatment with the preparation, 8 sixteen suicide attempts were made, two of these 9 with success. As patients with a risk of suicide 10 were excluded from the studies, it is probable 11 that this high proportion can be attributed to an 12 action of the preparation in the essence of -- in 13 the sense of a deterioration of the clinical 14 condition which reached its lowest point, end 15 quote, correct? 16 A. Yes. 17 Q. They're critical there too, 18 aren't they, Doctor? 19 A. Oh, yes, they are critical 20 there. 21 Q. And they're saying that the 22 sixteen suicide attempts that they saw in Lilly's 23 clinical data indicated to them that it was the 24 result of the preparation, fluoxetine Page 141 1 hydrochloride, correct? 2 A. That is what they say, yes. 3 Q. Then if you turn with me to 4 page four, they summarize their opinion and they 5 end it in point two by saying, considering the 6 benefit and the risk, we think this preparation 7 totally unsuitable for the treatment of 8 depression, end quote, don't they? 9 A. Yes. 10 Q. Not good news, right? 11 A. No, not at all. 12 Q. You've received a medical 13 opinion which indicates some substantial problems 14 with this product, haven't you? 15 A. Yes, which indicates an 16 opinion of the BGA some substantial problems, 17 yes. 18 Q. It's a scientific opinion, is 19 it not? 20 A. Yes. 21 Q. That this product presents 22 some problems for some patients, isn't it? 23 A. Yes. 24 Q. Whether or not it's right or Page 142 1 wrong, of course, is the subject of dispute, is 2 it not? 3 A. That is right. 4 Q. But it was raised in 1984, 5 wasn't it? 6 A. Yes. 7 Q. By scientists, medical 8 scientists in Germany. 9 A. By the medical reviewer of the 10 BGA, yes. 11 Q. Who is a scientist. 12 A. Who is a scientist. 13 Q. And charged with the 14 responsibility of reviewing this material. 15 A. Yes. 16 Q. Lilly material. 17 A. Yes. 18 Q. He's a person selected for 19 some degree of expertise in reviewing these types 20 of applications also, isn't he? 21 A. That is correct. 22 Q. Obviously I assume from Lilly 23 Germany's standpoint, this is going to present a 24 problem for approval of Prozac, is it not? Page 143 1 A. Oh, it has -- it was a problem 2 for approval, yes. 3 Q. If this medical opinion is 4 maintained, it's unlikely that this product is 5 going to be approved, correct? 6 A. That is correct. 7 Q. Some response was going to 8 have to be made, was it not? 9 A. Yes. 10 Q. Someone's response was going 11 to have to be made to the BGA. 12 A. Yes, that is necessary. 13 Q. And I assume this was Doctor 14 Schenk's responsibility -- 15 A. Right. 16 Q. -- locally in Germany? 17 A. Yes, that is right. 18 (PLAINTIFFS' EXHIBIT NO. 4 WAS 19 MARKED FOR IDENTIFICATION AND 20 RECEIVED IN EVIDENCE.) 21 A. Do you expect me to read all 22 of this? 23 Q. Yes, and we're going to give 24 you a test on it in a minute -- no, I'm teasing Page 144 1 you, Doctor. No, I just want to point out -- 2 first, take a look at it and review it to see if 3 you recognize it. 4 A. Right. 5 Q. And you might look through it 6 to familiarize yourself with it a little bit, but 7 I'm certainly not going to ask you questions in 8 detail about the total thing. 9 (WITNESS REVIEWS DOCUMENT.) 10 Q. I tell you what, Doctor, I 11 know you've got to get on the plane. Let me ask 12 you some general questions. It appears from 13 looking at this that Ms. Schenk drafted this 14 document, correct? 15 A. Yes. 16 Q. And it's entitled fluoxetine 17 reply to the medical opinion within the list of 18 concerns, correct? 19 A. Yes. 20 Q. And if you look at the medical 21 opinion there, you'll see that the subject matter 22 is basically the same. 23 A. Yes, yes, correct. 24 Q. And are you familiar with this Page 145 1 document, this Exhibit 4 I believe it is? 2 A. No, I am not, but it was a 3 basis for a reply, and I'm familiar with the 4 final document in German which was our reply. 5 Q. Well, did you review the 6 draft? It says it's a draft, it may have ended 7 up being the final product, I don't know, or the 8 final product may not have been changed. 9 A. No, it may have not, but maybe 10 some -- it says in here that it is not a perfect 11 version, so something probably was changed, but 12 as close to the final version as I can see. 13 Q. And this document is an 14 attempt to meet the issues raised by the medical 15 opinion at the BGA, is it not? 16 A. That's correct. 17 Q. So we'll be clear -- and it 18 says reply to the medical opinion within the list 19 of concerns, does it not? 20 A. Yes. 21 Q. All right. This document on 22 page -- I don't really see a numbered page. 23 A. No. 24 Q. But -- is there any numbers on Page 146 1 your page? 2 A. No, there's no numbers. 3 Q. There's some Pz numbers. Look 4 at Pz 1653. 5 A. Yes. 6 Q. Do you see that? 7 A. Yes. 8 Q. It says -- it appears that 9 she's describing the activity profiles of 10 antidepressant drugs, do you see that? 11 A. Yes, I see this. 12 Q. If you look toward the middle 13 of that first paragraph, it says the majority of 14 substances have an effect on one or more 15 transmitter substances, either by increasing the 16 concentration at the synaptic cleft by reuptake 17 inhibition or MAO inhibition or by blockade of 18 the post-synaptic receptors. Unfortunately there 19 exists no practicable routine method to identify 20 the possible underlying deficiency of a 21 neurotransmitter in a certain patient and a 22 causal relationship between primary action and 23 antidepressant potential is not yet established. 24 Therefore the choice of a specific antidepressant Page 147 1 will mainly depend upon the symptomatology and 2 the clinical profile of action of the respective 3 drug, end quote, correct? 4 A. Yes, that is correct. 5 Q. Do you think that's an 6 accurate statement of the science at that time? 7 A. I think it is an accurate 8 statement, yes. 9 Q. And still remains an accurate 10 statement concerning the science as we know it? 11 A. Time went on, you know a 12 little bit more, but it is very difficult to 13 predict how a drug may work upon just transmitter 14 information, yes. 15 Q. And she says unfortunately 16 there exists no practicable routine method to 17 identify the possibly underlying deficiency of a 18 neurotransmitter -- of a transmitter in a certain 19 patient, correct? 20 A. That is correct. 21 Q. In other words, there's a 22 presumption that people who are depressed are 23 depressed because they have a low level of 24 serotonin in the synaptic cleft, correct? Page 148 1 A. Yes. 2 Q. But there's not any 3 measurement that can be taken of a particular 4 patient at a particular time to get a particular 5 reading of what that concentration is at the 6 synaptic cleft? 7 A. That is right. 8 Q. And you know further from 9 studies that these concentrations vary, correct? 10 A. Yes. 11 Q. Within a patient? 12 A. Well, I don't know this, but -- 13 Q. That's the generally accepted 14 science in the area, is it not? 15 A. Uh-huh. 16 Q. By Doctors Fuller and Wong. 17 A. I'm not so aware about the 18 basic research of this, so I leave it to other 19 people. 20 Q. But you understand that this 21 is reflective of the assumption that we can't 22 measure exactly what the level of the 23 neurotransmitter is at the synaptic cleft? 24 A. I would agree with that, yes. Page 149 1 Q. And you don't know whether or 2 not there is a causal relationship between 3 primary action and antidepressant potential? 4 A. Right, I think that is right. 5 Q. In other words you're not sure 6 that in fact Prozac is causing people to become 7 less depressed because of the reduction in the 8 serotonin or the increase in serotonin at the 9 synaptic cleft? 10 A. I think that is correct, and 11 it doesn't work in thirty percent of patients. 12 Q. You say thirty percent of the 13 patients? 14 A. About thirty percent, yes. 15 Q. Is it your understanding, 16 Doctor Weber, that Prozac alleviates depressive 17 symptoms then in seventy percent of the patients 18 to whom it's given? 19 A. Yes. 20 Q. What clinical study or trial 21 have you seen that demonstrates seventy percent 22 efficacy of Prozac? 23 A. There are several studies 24 within the submission to the BGA, for example Page 150 1 were a number of studies, there was one major 2 study, the final study, for example, they had 3 German studies at the University of Muchein which 4 showed similar efficacy. 5 Q. Is it your testimony, Doctor 6 Weber, that it's your understanding that if I'm 7 depressed that I will have a seven in ten chance 8 of getting better by taking Prozac? 9 A. That is my understanding for 10 Prozac as well as for other antidepressants. 11 Q. All right. That brings up an 12 interesting statement. Is it your testimony that 13 Prozac is more or less effective in treating 14 depression than other antidepressants? 15 A. My understanding is that it's 16 the same. 17 Q. All right. But that any 18 antidepressant action -- any antidepressant will 19 be effective seventy percent of the time? 20 A. Yes. A single product did not 21 go much beyond the seventy percent. 22 Q. The difference, because the 23 antidepressants are equally efficacious, the 24 difference between those antidepressants is their Page 151 1 side effect profile, isn't it, Doctor Weber? 2 A. That is true, yes. 3 Q. And that gets us back to the 4 fact that Prozac produces nonsedating side 5 effects generally. 6 A. Nonsedating side effects. I 7 have a little difficulty what you mean by this. 8 Q. The package insert in your 9 homeland -- 10 A. Yes. 11 Q. -- Germany -- 12 A. Yes. 13 Q. -- indicates that Prozac is 14 generally not a sedating antidepressant, doesn't 15 it? 16 A. Yes, but this mean that it 17 doesn't have the side effect of being sedating. 18 Q. I understand that. 19 A. Right. 20 Q. But it's going to have more 21 activating side effects in more people than 22 sedating side effects in people, correct? 23 A. We had this point already 24 before, and I think it has agitation, nervousness Page 152 1 and insomnia, and when you take it as activation 2 then, that's right. It may also have sedation. 3 Q. Look on page sixteen sixty-two 4 of this response to the BGA medical comment. 5 A. Sixteen sixty-two? 6 Q. Yes. 7 A. Okay. 8 Q. There's a heading there that 9 is entitled Spectrum Of Adverse Events Which 10 Characterize Fluoxetine's Clinical Profile Of 11 Action (Regardless Of Severity), correct. 12 A. That is correct, it says 13 experiences. 14 Q. It says, those adverse 15 experiences which were frequently observed during 16 treatment with fluoxetine and were thought to be 17 perhaps related to activation are tabulated as 18 well as those adverse experiences which are known 19 to occur frequently during treatment with 20 tricyclic antidepressants, correct? 21 A. Yes. 22 Q. It says, on the one hand those 23 adverse experiences were anxiety, nervousness, 24 headache, insomnia, nausea, excessive sweating Page 153 1 and tremor, correct? 2 A. Yes, that is correct. 3 Q. And those have to do with 4 Prozac side effects, don't they? 5 A. Yes. 6 Q. It says on the tricyclic side, 7 those side effects were anticholinergic ones, 8 dizziness/lightheadedness and 9 drowsiness/sedation, right? 10 A. Yes, that is right. 11 Q. So she there has picked up 12 which side effects are activating and listed 13 them, hasn't she? 14 A. Well, yes. Some of them, for 15 example nausea or headache, I would not call 16 activating side effects. 17 Q. Those are side effects you see 18 with stimulant drugs though, aren't they, nausea 19 and headaches? 20 A. With stimulants? 21 Q. Yes. 22 A. Are you sure? Yes, maybe. 23 Q. Uh-huh. 24 A. I'm not so familiar. Page 154 1 Q. But you're a pharmacologist, 2 aren't you? 3 A. Yes, right. 4 Q. And stimulant drugs do cause 5 nausea and headaches, don't they? 6 A. I don't know. 7 Q. You just don't know? 8 A. No. 9 Q. You wouldn't be surprised, you 10 would disagree with testimony as to that, would 11 you? 12 A. What? 13 Q. That stimulant drugs cause 14 nausea and headaches. 15 A. I would not be surprised, that 16 is right. And certainly there are patients that 17 will experience headache and nausea under 18 stimulants, whether this is a high number, I 19 don't know. 20 Q. The response to the BGA goes 21 on and lists the side effects in connection with 22 Prozac, doesn't it? 23 A. Yes. 24 Q. Has the listing of anxiety/ Page 155 1 nervousness, doesn't it? 2 A. Yes. 3 Q. It says during treatment with 4 fluoxetine significantly more patients reported 5 anxiety/nervousness than patients on placebo and 6 Doxepin, doesn't it? 7 A. Yes. 8 Q. It says headaches. Says there 9 were no major differences to placebo and the 10 other comparative antidepressants except for 11 significantly more headaches in agitated 12 fluoxetine patients as compared to amitriptylene, 13 correct? 14 A. Yes. 15 Q. It says there were more 16 significant -- significantly more significant 17 headaches in the agitated Prozac patients than 18 those patients taking amitriptylene, correct? 19 A. It says this, yes. 20 Q. You don't disagree with any of 21 this, do you? 22 A. No, I can read it. 23 Q. It says insomnia, and she 24 lists a table there, doesn't she, table twelve? Page 156 1 A. Yes. 2 Q. It says fluoxetine causes 3 significantly more frequently insomnia than 4 placebo, amitriptylene and Doxepin, and slightly 5 more frequently than imipramine, doesn't it? 6 A. Yes. 7 Q. It looks like it beats 8 everybody there, doesn't it? 9 A. It beats -- 10 Q. It beats all the others, 11 placebo and all the comparators, as causing more 12 insomnia? 13 A. Yes. In some of them slightly 14 more, yes. 15 Q. You see insomnia with 16 stimulant drugs, don't you? 17 A. Certainly, yes. 18 Q. Nausea is on page sixteen 19 sixty-four as a side effect of Prozac. 20 A. Right. 21 Q. It says nausea is a common 22 adverse experience during fluoxetine treatment. 23 A. Yes. 24 Q. You see nausea in stimulant Page 157 1 drugs, don't you? 2 A. I do not know how severe it is 3 in the stimulant drugs, I mean nausea you can 4 have with a couple of drugs and it has nothing to 5 do with stimulation. 6 Q. Excessive sweating is the next 7 side effect listed, isn't it? 8 A. Yes. 9 Q. It says fluoxetine does cause 10 a significantly higher incidence of -- than 11 placebo, correct? 12 A. Yes. 13 Q. Excessive sweating is 14 something you see in a stimulant, isn't it? 15 A. You can see this with a 16 stimulant as well as with other drugs, yes. 17 Q. Do you see excessive sweating 18 generally with a sedative? 19 A. With a sedative that can 20 occur, yes. 21 Q. Tremors, it said tremors were 22 observed slightly more frequently during 23 treatment with fluoxetine, correct? 24 A. What does it say? Page 158 1 Q. It says tremors, although 2 tremors were observed significantly more 3 frequently during treatment with fluoxetine than 4 during placebo therapy, there was no difference 5 to the active comparators. 6 A. Yes. 7 Q. So there were more tremors on 8 patients taking Prozac than those that weren't 9 taking any antidepressant, wasn't there? 10 A. No, there were more tremor on 11 Prozac than on placebo. 12 Q. Which means patients not 13 taking any medication. 14 A. Okay, that is correct. 15 Q. That's what placebo means, 16 isn't it? 17 A. Yes. 18 Q. Then if you turn to page 19 sixteen sixty-six, you see that this draft 20 response to the medical opinion has a summary 21 concerning these particular side effects. 22 A. Yes. 23 Q. It says fluoxetine does induce 24 a different spectrum of adverse experiences as Page 159 1 compared to the sedating tricyclic 2 antidepressants, with usually more insomnia and 3 anxiety, nervousness and nausea, and much less 4 anticholinergic side effects and dizziness and 5 less drowsiness/sedation, correct? 6 A. That is correct. 7 Q. Then if you turn to the fourth 8 paragraph there, it says thus fluoxetine seems to 9 have mildly activating properties, doesn't it? 10 A. Yes. 11 Q. As far as you know, this went 12 to the BGA, didn't it? 13 A. No. That was, as it says at 14 the beginning, a draft which went to 15 Indianapolis, and on the basis of this we made 16 the final response. 17 Q. Did you make any changes in 18 anything I've read that you recall, Doctor Weber? 19 A. It is likely that we made 20 changes because the analysis of the data did not 21 really confirm that fluoxetine has activating 22 properties. 23 Q. What analysis? 24 A. I do not recall exactly the Page 160 1 analysis, but we analyzed mainly the final study 2 which was protocol twenty-seven as far as I 3 remember. 4 Q. Protocol twenty-seven? 5 A. It is somewhat a prominant 6 protocol, that's why I remember the number. 7 Q. You felt like -- your 8 recollection is that protocol number twenty-seven 9 was beneficial to Lilly in its presentation of 10 the properties of this drug -- 11 A. No. 12 Q. -- and it's potential? 13 A. No. It was the most -- it was 14 the best study which we had in terms that we had 15 appropriate patient numbers and this kind of 16 thing. We had -- I remember that we had one 17 study which was much more beneficial about 18 fluoxetine than the final study. 19 Q. Why don't you turn with me to 20 page sixteen fifty-three, Doctor Weber, I mean 21 because I think she may be looking at even more 22 data than protocol number twenty-seven. Look at 23 what she tells -- sixteen fifty-four -- us she 24 reviewed. When I say she, I don't know that it's Page 161 1 just Doctor Schenk that made this review, do you? 2 Can you help us on that? 3 A. It was to my recollection, 4 Doctor Schenk. 5 Q. She compiled this entire 6 document? 7 A. Probably, yes. 8 Q. Look what she says she 9 reviewed. She says she reviewed protocol 10 nineteen twenty-five, protocol twenty-seven, 11 protocols twenty-two, twenty-three, twenty-six, 12 protocol thirty-one, protocol thirty-three, 13 protocol twenty-nine, two studies, fluoxetine QD 14 versus BID, protocol thirty-five. 15 A. Uh-huh. 16 Q. That's a lot of data, isn't 17 it? 18 A. Yes. 19 Q. That even includes more data 20 than Doctor Finer's protocol number twenty-seven, 21 doesn't it? 22 A. Oh, certainly. 23 Q. Is it your testimony here that 24 Doctor Finer's data of protocol number Page 162 1 twenty-seven is more inclusive or less inclusive 2 than these -- well, let's just count them, one, 3 two, three, four, five, six, seven, eight, nine 4 other studies in addition to protocol number 5 twenty-seven? 6 A. Well, in my recollection, as I 7 said Finer had the highest patient numbers, which 8 means that the conclusions which can be drawn 9 from this study are much better than from any 10 other study in terms of statistics and so on. 11 The other studies in my recollection were smaller 12 studies and therefore more difficult to 13 interpret. 14 Q. But look at item two, she says 15 she does include protocol twenty-seven, doesn't 16 she? 17 A. Yes. 18 Q. So she's looking at all the 19 data -- 20 A. Right. 21 Q. -- there. 22 A. Right. 23 Q. Including Doctor Finer's data. 24 A. Of course, everyone was doing Page 163 1 it, all the studies were of course submitted to 2 the BGA. 3 Q. In fact, the response you're 4 making is based on the BGA's review of the data, 5 isn't it? 6 A. Yes. 7 Q. Which was data that you had 8 supplied to the BGA, correct? 9 A. Yes. 10 Q. Which included protocol number 11 twenty-seven -- 12 A. Yes. 13 Q. -- correct? 14 A. Yes. 15 Q. So now is it your testimony 16 now, Doctor Weber, that after this draft was done 17 there was additional data that was reviewed? 18 A. After this draft, additional 19 data? 20 Q. Yes, was reviewed and a 21 response made -- a different response made to the 22 BGA other than what we have marked here as 23 Exhibit 4? 24 A. It is -- as far as I know an Page 164 1 analysis have been made indeed because they were 2 requested by the BGA such data, like use of 3 concomitant drugs versus no concomitant drugs, 4 and especially when you go to subtypes of 5 patients which were requested by the BGA, for 6 example going to subtypes of retarded depression, 7 agitated depression, then the other studies are 8 very small, and the final study is the only one -- 9 or perhaps the only one, I do not recall all the 10 studies in detail, which provides good data also 11 to subtypes of patients. 12 Q. Well, did Finer categorize his 13 patients into these subcategories? He didn't. 14 A. Yes. Why do you say he 15 didn't? 16 Q. Because Doctor Beasley 17 reviewed it in 1990 and said under oath here that 18 he didn't. 19 MR. MYERS: I object to the form, you 20 micharacterized what Doctor Beasley said. 21 Doctor, you don't have to accept anything Mr. 22 Smith says is true. If you know it to be true, 23 tell him that. 24 A. I think the studies were not Page 165 1 necessarily designed in a way to study subtypes 2 of depression, but as the questionnaires and the 3 so-called case report forms were collecting the 4 data so that you could do it. 5 Q. But that data was before the 6 BGA, wasn't it? Protocol number twenty-seven was 7 submitted to the BGA. 8 A. Yes. 9 Q. Protocol number twenty-seven 10 was what Lilly thought supported claims of 11 efficacy and safety, correct? 12 A. That is correct, yes. 13 Q. And that's what this document 14 is including, isn't it? Don't you see here where 15 it says item two, protocol number twenty-seven? 16 A. Yes, it is included, yes. 17 Q. So are you saying there was a 18 reanalysis of protocol number twenty-seven after 19 this document was made? 20 A. No, I would say additional 21 analysis was made. 22 Q. An additional analysis. 23 A. Right. 24 Q. But the data was all the same, Page 166 1 wasn't it? 2 A. The data was all the same. 3 Q. And has been the same from the 4 outset. 5 A. I think that is true. I mean 6 I was not involved in all of the details but, 7 yes, I would say yes. 8 Q. As the medical director for 9 Eli Lilly and Company in Germany, did you not 10 review this document, Doctor Weber? 11 A. Which document do you mean, 12 the document of Johanna Schenk? 13 Q. Yes, the document that's in 14 front of you. 15 A. Before she sent it to 16 Indianapolis? 17 Q. Yes. 18 A. Yes, I have seen it and 19 reviewed it, yes. 20 Q. You approved it before she 21 sent it to Indianapolis, didn't you, Doctor? 22 A. Yes. 23 Q. Now are you saying that this 24 is incorrect? Page 167 1 MR. MYERS: Let me object to the form. 2 When you say this is incorrect, what is 3 incorrect? 4 MR. SMITH: Exhibit 4, what we're 5 looking at, what he's looking at, Counsel. You 6 can see it. 7 MR. MYERS: What part, Mr. Smith, what 8 part of Exhibit 4? 9 MR. SMITH: Anything in here that 10 we've mentioned. 11 A. Well, it was what we with our 12 tools could figure out. 13 Q. It was the best you could do 14 at the time under the circumstances, correct? 15 A. Yes. 16 Q. And you were expressing what 17 you thought was good scientific analysis at the 18 time, correct, Doctor Weber? 19 A. Was it good scientific 20 analysis, I mean that was as we saw the data and 21 reviewed the data. Neither Johanna Schenk nor I 22 am psychiatrists, nor are we specialists of 23 analysis, for example we do not have a 24 statistician available in our office in Bad Page 168 1 Homburg. But that is obviously what we -- what 2 we could best make out of the data and which was 3 a proposal to Indianapolis, how we could look at 4 the data. I think that Indianapolis certainly at 5 this point in time was much more familiar with 6 the data and much more professional about it than 7 we were. 8 Q. Do you think this is a shoddy 9 piece of work? 10 A. No, I don't think so. I think -- 11 and that is I think a little bit German behavior, 12 we are very critical about ourselves and it is a 13 way to also address the difficulties and to ask 14 Indianapolis to review it and whether it is 15 correct or we have to do something in addition. 16 Q. Did Indianapolis review this 17 document? 18 A. Yes, certainly they did. 19 Q. What major changes were made 20 in this document before it was submitted to the 21 BGA, Doctor Weber? 22 A. We have here now not read the 23 whole document. 24 Q. That probably is an unfair Page 169 1 question. Do you know based on your recollection 2 now of any changes that come to mind that were 3 made off this original draft? 4 A. I know there are no particular 5 changes which I have in mind. Certainly we have 6 changed what I just have read that was what is 7 stated in the summary, that Fluctin would be -- 8 or Prozac would be activating. 9 Q. You say that Lilly has changed 10 their position that Prozac is activating? 11 A. Not Lilly has changed the 12 position. 13 Q. You or who? 14 A. The draft was changed in this 15 respect, yes. 16 Q. It was not submitted to the 17 BGA that Prozac was an activating antidepressant? 18 A. No. 19 Q. All right. Let's go back, 20 let's go -- this -- one of the issues, there was 21 a serious problem in view of the BGA was the 22 issue of suicide in connection with the use of 23 Prozac, correct? 24 A. Yes. Page 170 1 Q. And this is addressed here 2 also, isn't it? 3 A. Certainly it is, yes. We 4 haven't looked at it, but -- 5 Q. I'm going to point you where 6 it is. Suicidal risk specifically starts on page 7 sixteen ninety-one. And why don't you take a 8 minute to glance at that because I do not want to 9 be unfair with you, Doctor Weber. I'm not going 10 to ask you specific questions about every 11 sentence and page, but feel free to glance at it. 12 A. I'll read it. 13 Q. Now the BGA had raised the 14 proposition that Prozac was causing suicidality 15 because people with serious suicidal risk had 16 been excluded from the clinical trial and this 17 was a high number of suicides, correct? 18 A. Say this again, I didn't get 19 it. 20 Q. I may not have said that 21 right. The BGA was concerned that Prozac might 22 be causing suicide? 23 A. Yes. 24 Q. Or at least increasing the Page 171 1 risk in suicidal patients, correct? 2 A. Yes. 3 Q. The reason that they express 4 in their medical opinion was is that you had 5 sixteen suicide attempts by patients taking 6 Prozac in the clinical trials and the clinical 7 trials had excluded individuals who were a 8 serious suicidal risk, right? 9 A. We had sixteen patients with 10 suicides in the trials and yes, the other what 11 you said is correct. 12 Q. And they were taking Prozac 13 too, weren't they? 14 A. Not all of them. 15 Q. Well, there's some question 16 maybe one or two of them. 17 A. That's right. 18 Q. But that's still, even if you 19 exclude those that are mentioned in this 20 response, a significant number of individuals, is 21 it not? 22 A. Yes, it is. 23 Q. All right. Doctor Schenk and 24 I suppose you to some extent make an analysis of Page 172 1 this question and conclude on page sixteen 2 ninety-five, from the number of suicides/suicide 3 attempts during clinical trials with fluoxetine 4 and the time of trial when they happened, a 5 higher incidence of suicide attempts during 6 treatment with this antidepressant cannot be 7 derived. 8 A. Yes. 9 Q. On the other hand, the HAMD 10 factor suicidal tendencies might be more improved 11 by sedating antidepressants at the early stages 12 of treatment, although fluoxetine is of course 13 significantly better than placebo. These 14 findings underline the dogma that, if at all, 15 activating antidepressants should only be used 16 with caution in suicidal patients at best with 17 concurrent administration of sedating drugs. The 18 latter can be omitted at the time of sufficient 19 alleviation -- elevation of depressed mood, end 20 quote, correct? 21 A. Yes. 22 Q. Was that Lilly Germany's 23 opinion at the time that this was written? 24 A. I would not necessarily say Page 173 1 that it was our opinion. First of all, I would 2 say today I think we came to the wrong 3 conclusion. Furthermore -- 4 Q. Why? 5 A. Because when you try to 6 convince the BGA about the approval of the drug, 7 you have different choices. You can convince 8 them this data and reply to the questions. What 9 you also can do is to make statements in the 10 labeling which then may eliminate their concerns. 11 So it has been one of our thinking at one point 12 of time, should we perhaps admit something of 13 this nature what the BGA was asking us to make 14 the approval earlier, but we came later to the 15 conclusion that that was not -- that this would 16 not have been a good choice, and that we should 17 rely on the data which we have. I think the 18 conclusion -- the reason that we came to this 19 conclusion was a lack of statistical experience 20 at this point of time. 21 MR. SMITH: I object to the answer as 22 being nonresponsive. 23 Q. My question to you, Doctor 24 Weber, is was that your opinion at the time it Page 174 1 was written? 2 A. Was this my opinion -- that is 3 a very difficult answer. I did not know at this 4 time. I took the question about suicidality 5 serious, I thought we had to reply to that in the 6 most serious way taking into account that this 7 might be a possibility. 8 Q. That Prozac increased suicidal 9 risk? 10 A. We were taking this into 11 account at this point in time, yes. 12 Q. You see, what you say here or 13 what Doctor Schenk says with your approval, I'm 14 sure -- 15 A. Yes. 16 Q. -- was that, quote, these 17 findings underline the dogma that if at all, 18 activating antidepressants should be used only 19 with caution in suicidal patients. At best, with 20 concurrent administrative -- administration of 21 sedating drugs, correct? 22 A. Yes. 23 Q. Did you feel that sentence 24 that I just quoted you was incorrect? Page 175 1 A. I can either say that I felt 2 at this point in time that it was correct or that 3 it was incorrect. 4 Q. This is what at least was 5 intended at the time to be sent to the BGA, 6 wasn't it? 7 MR. MYERS: Before you answer that 8 question, Mr. Smith interrupted you. Finish your 9 last answer and then answer his question. 10 A. I think what I wanted to say 11 is that I know Johanna Schenk very well and she 12 is an aggressive lady and aggressive to the 13 company in a way to really point the company down 14 to get a reasonable reply, and sometimes she 15 makes such aggressive statements. I think that I 16 at the point of time was not convinced that this 17 was right, but I agreed to go ahead to make this 18 statement to Indianapolis and see whether 19 Indianapolis would reply about the statement. 20 That was not at this point of time intended to go 21 to the BGA and to be the truth. 22 Q. In fact, Doctor Weber, this is 23 what came out in the BGA approval process, isn't 24 it? Page 176 1 A. That was a point of 2 negotiation between Lilly Germany and 3 Indianapolis. 4 Q. Between Lilly Germany and 5 Indianapolis? 6 A. Right. In preparation of a 7 response to the BGA. 8 Q. This was what was submitted to 9 the BGA, isn't it? 10 A. I do not think that this was 11 submitted to the BGA, no. 12 Q. But what the package insert 13 says is what this says, isn't it? 14 MR. MYERS: Let me object to the form 15 to the extent it assumes that they are identical. 16 Go ahead and answer, Doctor. 17 Q. Well, you have the German 18 package insert in front of you if you'd like to 19 compare. 20 A. The package insert does not 21 say anything as far as I remember about 22 activating antidepressants. 23 Q. It says that Prozac isn't a 24 sedating antidepressant, doesn't it? Page 177 1 A. This is different. 2 Q. Well, it says that Prozac 3 should be used with caution in suicidal patients, 4 doesn't it? 5 A. Yes. 6 Q. It says that the physician 7 should consider concurrent administration of 8 sedative properties, doesn't it -- sedative 9 drugs, doesn't it? 10 A. Yes. 11 Q. Until the antidepressant 12 activity of Prozac sets in, doesn't it? 13 A. Yes. 14 Q. It's very similar to what is 15 said here, isn't it, Doctor Weber? 16 A. Yes, and it is in some ways 17 similar, but there's also an important difference 18 and that is that the labeling does not talk about 19 an activating antidepressant. 20 Q. Look at the paragraph, look at 21 the paragraph there that you and Doctor Schenk 22 sent to Indianapolis. 23 A. Right. 24 Q. It says these findings Page 178 1 underline the dogma that if at all, activating 2 antidepressants should only be used with caution 3 in suicidal patients. Do you see that? 4 A. Yes. 5 Q. Is that an incorrect statement 6 of medicine? 7 A. No, that is the old tradition 8 of German psychiatry, that drugs may be sedating 9 or activating and that you -- when you have a 10 patient at risk of suicide, you usually should 11 not take an activating product. 12 Q. Is that wrong? 13 MR. MYERS: Wait a minute, Paul, you 14 cut him off again. 15 Q. Excuse me, I'm sorry, Doctor 16 Weber, I didn't realize, I thought you were 17 finished. I apologize. 18 A. That is related to the 19 knowledge or to the tradition of, as I said, 20 through tradition of psychiatry in Germany. 21 Q. Was that wrong? 22 A. Excuse me? 23 Q. Is that wrong that an 24 activating antidepressant should only be used Page 179 1 with caution in suicidal patients? 2 A. Actually, I don't know. The 3 theory in Germany is that you have to put any 4 drug on as an activating or sedating product is 5 today somewhat under debate. I think that most 6 of the psychiatric experts say that first of all, 7 any antidepressant decreases suicide and not 8 increases suicide compared to placebo. 9 Q. So it's -- this was an 10 incorrect statement of science then when the 11 draft recommendation said, if at all, activating 12 antidepressants should be used with caution in 13 suicidal patients? 14 A. No, that statement in general 15 is still valid. 16 Q. There's also the statement 17 here that with this activating antidepressant 18 that there should be concurrent administration of 19 sedating drugs and that the sedating drugs can be 20 admitted after sufficient elevation of depressive 21 mood, correct? 22 A. Yes. 23 Q. Is that an incorrect statement 24 of medicine? Page 180 1 A. I think that again, in 2 general, it is the education in Germany that 3 patients at risk of suicidality may need a 4 sedative. 5 Q. So basically if you look at 6 that paragraph all you were saying to Lilly was 7 an accurate reflection of the state of the 8 knowledge of medicine at the time, correct? 9 A. In general, that is okay. I 10 think the big difference is that nothing has 11 changed about this information in general, 12 however, it has nothing to do with the drug 13 itself. 14 Q. Did you and Doctor Schenk have 15 a debate about this? 16 A. Actually we had many debates. 17 We had sometimes different opinions. I was a 18 little less sharp on this issue than Johanna 19 Schenk was. 20 Q. When you say sharp, what do 21 you mean? 22 A. Sharp regarding this specific 23 sentences regarding suicidality and whether -- 24 what is written here, I was less sharp in a way Page 181 1 that I felt I just don't know. 2 Q. You felt that she had more 3 knowledge concerning these matters than you 4 because she was the one that had been 5 specifically assigned the task of monitoring 6 Prozac in Germany? 7 A. She was closer to the data and 8 I felt it was appropriate to test her position. 9 Q. So you deferred to her 10 judgment in that recommendation -- 11 A. Yes. 12 Q. -- concerning the use of 13 Prozac? 14 A. Yes. 15 Q. Because she had been the one 16 that had been wading through the data, correct? 17 A. That is correct. 18 Q. And she appeared to be making 19 a careful analysis of this issue, correct? 20 A. That is correct. 21 Q. What did she spend, weeks, 22 days or hours in preparing this draft? 23 A. Unfortunately only days 24 because we had not much time. Page 182 1 Q. But she took great interest in 2 this during those days it took her to prepare 3 this draft? 4 A. Yes. 5 Q. And I didn't see in all the 6 documents that we've received any request from 7 her or you that you be given more time to submit 8 the draft. 9 A. That we were given more time? 10 Q. That you asked for more time 11 to submit this. 12 A. At this point of time, no, no. 13 Our initial response to the initial letter of 14 concerns was done under some time fashion, yes. 15 Q. But not this? 16 A. Well, that is a draft of the 17 first response. 18 Q. All right. But you don't 19 remember seeing any errors in this document, do 20 you? 21 A. Yes, I think there were some 22 errors. I think we later on the basis of data 23 and careful statistical analysis came to a 24 different conclusion, that fluoxetine is not Page 183 1 activating. We have not seen the comfort of 2 having statistical analysis available in our 3 office. 4 Q. There might be some debate. 5 You think that statistical analysis gives comfort 6 to a review of a scientific subject? 7 A. Not always. 8 Q. Do you know of any massaging 9 of any data that occurred in connection with the 10 statistical analysis of these issues? 11 A. No. 12 Q. Do you know Doctor Wernicke? 13 A. Yes. 14 Q. He's a native of Germany, I 15 believe. I think he's a United States citizen, 16 but I think he was born in Germany. 17 A. I think he has some relatives 18 in Germany, yes. 19 Q. Did you and he visit maybe on 20 occasion when he would come to Germany to visit 21 his relatives? 22 A. Infrequently, but yes, he came 23 to Germany. 24 Q. You and he ever hear of any Page 184 1 massaging of any data in connection with any work 2 that he did? 3 A. What do you mean by massaging? 4 I mean you can take the data, of course, which 5 you have and look as I said at subtypes, or you 6 can look at the data in different ways trying to 7 respond to specific questions which you perhaps 8 had not in the beginning. 9 Q. I guess massaging data in the 10 sense that making that data appear to be 11 something different than it really is. 12 A. No, I do not think that this 13 happened. 14 Q. You don't think it happened? 15 A. I think it did not happen. 16 Q. All right. Was there a 17 careful statistical analysis made of this data 18 before the final draft was submitted to the BGA, 19 before the formal response was submitted to the 20 BGA? 21 A. It's quite long ago and I'm 22 sure that after we made the draft, we received 23 additional information from Indianapolis, and 24 since the draft was in some respect rewritten, Page 185 1 but I'm not aware of specific analysis at this 2 point of time. Analysis of suicidality has 3 probably been made and said that there was no 4 statistical significant difference in the 5 different groups of treatment. 6 Q. You think that was added on to 7 this opinion? 8 A. That was? 9 Q. You think that was submitted 10 formally? 11 A. I think, yes. 12 Q. Look at the last paragraph. 13 A. Of the document? 14 Q. Yes. 15 A. Yes. 16 Q. The last paragraph says if the 17 drug is used according to the revised package 18 literature, that is in agitated and suicidal 19 patients only together with concomitant sedative 20 drugs, there should be no doubt on fluoxetine's 21 positive benefit/risk ratio in the treatment of 22 depression, end quote, correct? 23 A. Correct. 24 Q. Do you agree with that Page 186 1 proposition, Doctor Weber? 2 A. No. 3 Q. Did you agree with it then? 4 A. No, but -- 5 Q. Why did you let her send it? 6 A. I agreed to test this 7 statement and negotiate it with Indianapolis. 8 Q. So there was some negotiation 9 that went on in connection with the document 10 entitled, Fluoxetine, Reply To The Medical 11 Opinion Within the "List Of Concerns," correct? 12 A. Yes. 13 Q. I assume since there was 14 negotiating that there were people that were 15 taking divergent opinions concerning what type of 16 response should be made and what should be 17 submitted in the response? 18 A. Yes. 19 Q. Who was taking which side? 20 A. I think first of all it is 21 important to see the data and to get the real 22 data, and Indianapolis made the statement that 23 our data does not support such a statement, to 24 give fluoxetine only with concomitant sedative Page 187 1 drugs. 2 Q. Well, were there any studies, 3 Doctor Weber, where Prozac was used in agitated 4 and suicidal patients together with concomitant 5 medications? 6 A. Well, that's -- we had studies 7 in patients at suicidal risk, therefore 8 fluoxetine has used alone or with concomitant 9 medication on -- dependent upon the decision of 10 the investigator. 11 Q. Well now we know that there 12 was concomitant medication used throughout the 13 clinical trials, but my question to you is, were 14 there any clinical trials conducted by Lilly by 15 1984 that tested the hypothesis that Prozac was 16 more or less likely to cause suicidality if it 17 were used only in connection with a concomitant 18 sedative medication? 19 A. Studies of this nature with 20 this question did not exist. 21 Q. All right. So there weren't 22 any studies that proved this paragraph wrong, was 23 there, done by Lilly? 24 A. Yes, there were studies. That Page 188 1 was exactly why we requested to make an 2 additional analysis of patients with concomitant 3 medication and without concomitant medication. 4 Q. I'm not sure I understand. 5 Are you telling me that Doctor Schenk went 6 throughout these studies that she mentions here -- 7 how many did we we count, eight different 8 studies, nine different studies? 9 A. I think about that. 10 Q. Nine different protocols? 11 A. I think about eight protocols 12 as far as I recall. 13 Q. And made -- she made that 14 analysis, she looked at that, didn't she? 15 A. Yes. 16 Q. And she's the one that still 17 recommends that if Prozac is used in accordance 18 with the package literature, that is in agitated 19 and suicidal patients only, with concomitant 20 medications, sedative drugs, there should be no 21 doubt about the risk/benefit ratio, correct? 22 A. She makes the statement. I 23 think that the statement is -- was one 24 opportunity to go back to the BGA in order to Page 189 1 ease the approval of this medication, but we felt 2 after careful negotiation and looking at the data 3 that this is -- that this would not have been 4 appropriate. 5 (A SHORT RECESS WAS TAKEN.) 6 Q. (BY MR. SMITH) In this debate 7 in connection with whether or not Prozac was an 8 activating or sedating antidepressant, was that 9 the subject of the debate? 10 A. Yes, it was subject of the 11 debate. 12 Q. And there was -- would you 13 agree with me that there was data that supported 14 both sides of the debate to some extent? 15 A. There were some patients 16 obviously where it was activating. 17 Q. And in those patients that it 18 was activating, there was definite evidence of 19 activation, was there not? It was clear in some 20 patients that they were becoming activated by 21 virtue of their injection of Prozac? 22 A. Well, we had patients which 23 under treatment of Prozac had signs -- symptoms 24 of activation. Page 190 1 Q. Those were legitimate symptoms 2 of activation? 3 A. Such as we talked before, 4 anxiety or nervousness, agitation. 5 Q. And caused legitimate 6 physicians to draw the conclusion that these 7 patients were becoming activated on the 8 medication? 9 A. Well, as I said before, I, 10 myself -- I'm not a psychiatrist, but I, myself, 11 feel that agitation and activation is a little 12 bit different. 13 Q. I'm not concerned about that, 14 I'm talking about this debate -- 15 A. Yes. 16 Q. -- that was apparently -- 17 A. Yes. 18 Q. -- ongoing at this time. 19 A. Okay. 20 Q. I mean there was some 21 legitimate Lilly physicians, were there not -- 22 A. Yes. 23 Q. -- that legitimately felt 24 based on good medical observations that these Page 191 1 patients were becoming activated on Prozac, 2 correct? 3 A. Yes. 4 Q. There were other legitimate 5 physicians that indicated they weren't so sure 6 about that, correct? 7 A. Well, I would phrase it a 8 little bit different. To say -- the question was 9 really, was fluoxetine in general an activating 10 drug, yes or no, and the conclusion we reached 11 was that it was not an activating drug which does 12 not exclude that in some patients it might be 13 activating. 14 Q. Wasn't in general the data 15 reflective that the medication was activating as 16 a side effect in more individuals than it was 17 sedating in individuals? 18 A. There was a slight tendency 19 that the rate of activation was higher than that 20 of sedation, right, but the majority of patients 21 did not have neither sedation nor activation. 22 Q. Well, as a side effect. 23 A. As a side effect, yes. But to 24 have neither is not a side effect, certainly. Page 192 1 Q. The fact is that if a patient 2 is becoming agitated or generally -- or jittery, 3 they're more likely to become suicidal, isn't 4 that correct? 5 A. I think that agitation has not -- 6 as far as I understand it, agitation is not to do 7 with suicides. Patients commit suicides when 8 they are depressed because they feel to be 9 useless. 10 Q. You're going to have to defer 11 to the psychiatrists on that, are you not? 12 A. Yes. 13 Q. And you're going to have to 14 defer in fact to members of the Lilly psychiatric 15 advisory board on that, aren't you? 16 A. And on experts, external 17 experts in Germany. 18 Q. Do you know who Doctor Jan 19 Fawcett is, Doctor Weber? 20 A. Do you know who Doctor -- 21 Q. Jan Fawcett is? 22 A. J-N -- 23 Q. J-A-N, Fawcett, F-A-W-C-E-T-T. 24 A. No, I have not heard the Page 193 1 doctor's name. 2 Q. He's a member of the Lilly 3 Psychiatric Advisory Board. 4 A. Uh-huh. 5 Q. He's also an expert on 6 suicide. He has written in medical journals that 7 it's recommended if a patient becomes jittery, 8 that is becomes jittery while on fluoxetine, that 9 they should be given benzodiazepines. Were you 10 aware of that? 11 A. No, I'm not aware of this. 12 But in any patient who is jittery, a sedative may 13 be reasonable, yes. 14 Q. And may reduce the risk of 15 suicide? 16 A. While it is a general 17 understanding that in patients at risk of 18 suicide, you have to be especially careful and a 19 sedative may be advisable. 20 Q. That's what this last 21 paragraph is saying, isn't it? 22 A. No, the last -- no, this last 23 paragraph says something different. It says that 24 in all agitated patients -- Page 194 1 Q. I don't see the word all 2 there, do you see it? 3 A. No, I don't see the word all, 4 but it says in agitated and suicidal patients -- 5 I'll read it altogether. If the drug is used 6 according to the revised package literature, for 7 example in agitated or suicidal patients only, 8 together with concomitant sedative drugs, there 9 should be no doubt on fluoxetine's positive 10 benefit/risk ratio in the treatment of 11 depression. 12 Q. Don't you agree, Doctor Weber, 13 that if you're looking at the benefit/risk ratio 14 of Prozac, it would be preferable if the patient 15 is agitated or suicidal that they have 16 concomitant sedative medication? 17 A. Yes. As I said, that might be 18 recommended in some cases, and that is a decision 19 of the physician I believe. 20 Q. Don't you think the physician 21 should be advised that if the antidepressant is 22 in fact activating, that the physician should 23 consider concomitant use of sedatives? 24 A. If a drug is activating, it's Page 195 1 a general medical understanding that a sedative 2 might be helpful. 3 Q. And your disagreement here 4 then is only whether or not Prozac is activating? 5 A. Yes, whether Prozac is 6 activating and whether it should be taken in 7 every patient. 8 Q. This doesn't say every 9 patient, does it? 10 A. Well, when you say in agitated 11 and suicidal patients only together with 12 concomitant sedative drugs, that says basically 13 in every patient, isn't it? Only together -- 14 Q. Why don't you read the German 15 package insert that finally was published when 16 this drug was finally approved in Germany. 17 A. Right, uh-huh. 18 MR. MYERS: Is that a question? 19 Q. Yes, why don't you read it. 20 A. Yes. 21 Q. What does it say? 22 A. It says that a sedative -- the 23 concomitant use of sedative medication may be 24 necessary. Page 196 1 Q. Do you have any problems with 2 that instruction in the German package insert, 3 Doctor Weber? 4 A. No, I do not have any 5 difficulty with that. 6 Q. Not much distinction in what 7 that says and what the final paragraph in this 8 draft to the BGA says, is there? 9 A. I think as this says in 10 agitated and suicidal patients only together with 11 concomitant sedative drugs. And there is a 12 difference. We say not only to use Fluctin 13 together with sedative drugs, it is not said in 14 the final wording. 15 (DISCUSSION OFF THE RECORD.) 16 (PLAINTIFFS' EXHIBIT NO. 5 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.). 19 Q. (BY MR. SMITH) Let me 20 interrupt you while you're looking at that next 21 document, Doctor Weber. Had you seen Exhibit 4 22 before today? 23 A. You mean Exhibit 5? 24 Q. No, the one we were just Page 197 1 talking about, the draft. 2 A. No. 3 Q. You had not seen that before 4 today? 5 A. No. 6 Q. Well, I guess you had seen the 7 German version of it when it was -- 8 A. Long time ago, yes. 9 Q. Long time ago. This wasn't a 10 document you reviewed in preparation for your 11 deposition? 12 A. I did not review it in 13 preparation for this deposition, neither in 14 English nor in German. So my recollection is it 15 is now ten years ago. 16 Q. Exhibit 5 is a document 17 authored by you dated February 27, 1985. 18 A. Yes. 19 Q. And along with it is the 20 official intent to reject from the BGA, correct? 21 A. Yes. 22 Q. Now apparently you had sent a 23 response to the BGA's medical opinion, correct? 24 A. Yes. Page 198 1 Q. And in fact the response was 2 not sufficient, the BGA -- 3 A. Yes. 4 Q. -- decided not to accept the 5 application. 6 A. That is correct. 7 Q. And in fact because of the 8 concerns raised, told you they intended to reject 9 the application. 10 A. That is correct. 11 Q. And your letter of February 27 12 is transmitting that document, is it not? 13 A. Transmitting the -- 14 Q. The official intent-to-reject 15 letter. 16 A. This official intent-to-reject 17 letter, yes. 18 Q. It says you will find attached 19 the BGA response letter that was received today. 20 A. Yes. 21 Q. The letter is indeed an 22 intention of rejection, correct? 23 A. Yes. 24 Q. It indicates that there were -- Page 199 1 compared to the first letter of concerns, there 2 are many points that were raised originally. 3 A. Yes. 4 Q. And that in fact suicide was 5 still a reason given as an intent to reject this 6 product in Germany. 7 A. Yes. 8 Q. And in fact that had been 9 predicted to you, had it not? 10 A. It had been predicted that the 11 BGA -- 12 Q. Would reject your application. 13 A. Because of suicides? 14 Q. Yes. 15 A. No. 16 Q. Well, it says the letter from 17 the BGA is nearly identical with the opinions of 18 Professor Herrmann, whom Doctor H. J. Weber and 19 S. Heymanns visited the day before. According to 20 his opinion the following problems exist, 21 correct? 22 A. Okay, since twenty-four hours 23 it was not a surprise, yes, but before we had not 24 predicted this. Page 200 1 Q. But Doctor Herrmann had 2 predicted that. 3 A. Yes. 4 Q. Doctor Herrmann saw suicide as 5 a problem in reviewing this data, did he not? 6 A. Doctor Herrmann saw suicides 7 might be a problem, that is correct. 8 Q. And he was a consultant that 9 you had called in to advise you on the issue. 10 A. Yes. I mean suicides were not 11 the only problem, but it was one of several 12 issues where he felt that we might have 13 difficulties with approval, that's correct. 14 Q. And if you look over at the 15 document that rejects -- is your intent to reject 16 this application. 17 A. Right. 18 Q. If you look at section two 19 point one, it specifically says, the use of the 20 preparation seems objectionable as the increase 21 in agitating effect occurs earlier than the 22 mood-elevating effect, and therefore an increased 23 risk of suicide exists, end quote, does it not? 24 A. Yes, it says this. And I Page 201 1 would like to add that the translation of 2 agitating is here incorrect, it should have said 3 activating or energizing would have been the more 4 correct translation. 5 Q. Oh, really? 6 A. Yes. 7 Q. Well, I can -- I don't read 8 German. Is there an improper translation here? 9 A. We would translate it today a 10 little different, yes. 11 Q. Who translated it originally? 12 A. Probably a person in our 13 building. 14 Q. Well, you transmitted it, 15 didn't you? 16 A. Yes. 17 Q. To Indianapolis? 18 A. Yes. 19 Q. This is what the corporation 20 relied on when they received it here in 21 Indianapolis, isn't it, what we see here? 22 A. Yes. 23 Q. Written in English. 24 A. Right, right, right. Page 202 1 Q. You read the original German 2 intent-to-reject letter? 3 A. Yes. 4 Q. Is it your testimony here 5 today that section two point one should read, 6 energizing effect should in fact be -- should be -- 7 A. It should read instead of 8 agitating, more energizing or perhaps activating. 9 Q. It should read activating or 10 energizing instead of agitating? 11 A. Yes. 12 Q. All right. So it's your 13 recollection that the BGA in their intent to 14 reject this product says the use of the 15 preparation seems objectionable as the increase 16 in energizing or activating effect occurs earlier 17 than the mood-elevating effect, and therefore an 18 increased risk of suicide exists? 19 A. Yes. 20 Q. So what Doctor Herrmann 21 predicted that this could be rejected because of 22 this suicide issue did in fact occur? 23 A. You say because of suicide. 24 Suicidality is one of the issues, yes. Page 203 1 Q. Well, the other issues is, 2 they say in number one that the drugs concerned 3 are not sufficiently tested according to the 4 secured state of scientific knowledge, and that 5 therapeutic efficacy which is claimed for them is 6 insufficiently established, don't they? 7 A. They say this, yes. 8 Q. They say in point two, the 9 drug concerned -- for the drugs concerned, there 10 is according to their specific profile of adverse 11 effects the justified suspicion that they have 12 unacceptable damaging effects. 13 A. Yes. 14 Q. Point two point two says 15 during treatment with the drug, some symptoms of 16 the underlying disease (anxiety, insomnia, 17 agitation) increases, which as an adverse effect 18 exceed those which are considered acceptable by 19 medical standards, doesn't it? 20 A. It says that, yes. 21 Q. You had as I understand it -- 22 or did the final version of the response to the 23 BGA include a paragraph stating that Prozac 24 should be used with concomitant sedative Page 204 1 medication in suicidal or agitated patients? 2 A. I do not remember such a 3 statement. 4 Q. There is no statement in the 5 formal intent-to-reject letter, is there, that 6 Prozac would be acceptable if it was used in 7 connection with concomitant sedative medications 8 in some patients, is there? 9 A. No, there is no such 10 statement. 11 Q. The statement made by the BGA 12 in their formal intent-to-reject letter is that 13 the use of the preparation seems objectionable as 14 the increase in agitating effect occurs earlier 15 than the mood-elevating effect, and therefore an 16 increased risk of suicide exists, end quote, 17 correct? 18 A. Yes. 19 Q. Now you had an expert that was 20 reviewing this issue. 21 A. Uh-huh, yes. 22 Q. Lilly statisticians had 23 reviewed the original data when it was submitted 24 to them by the investigators, I assume? Page 205 1 A. Lilly's -- say that again? 2 Q. Did the clinical trials -- 3 A. Yes. 4 Q. -- correct? 5 A. Right. 6 Q. The clinical trial reports 7 were sent to Indianapolis, correct? 8 A. Yes. 9 Q. Indianapolis felt that that 10 data supported claims of safety and efficacy of 11 the product. 12 A. That's right. 13 Q. Lilly made the marketing 14 decision to provide -- to apply for registration 15 of Prozac in Germany. 16 A. Yes. 17 Q. It was going to be called 18 Fluctin in Germany. 19 A. Yes. 20 Q. And they submitted that data -- 21 Lilly submitted that data to the BGA -- 22 A. Yes. 23 Q. -- correct? 24 A. That is correct. Page 206 1 Q. The BGA reviewed that data. 2 A. Yes. 3 Q. The BGA had a Commission A 4 that reviewed that data. 5 A. Probably at this time, that is 6 correct. 7 Q. There's not any change, all 8 that data is the same, isn't it? 9 A. Yes. 10 Q. Then the BGA sends a medical 11 opinion, do they not? 12 A. Yes. 13 Q. That concludes that the 14 product is totally worthless for treatment of 15 depression, doesn't it? 16 MR. MYERS: Let me object to the form 17 of the question. 18 MR. SMITH: Then let's get it and read 19 it exactly. 20 MR. MYERS: What do you want to look 21 at? 22 MR. SMITH: The medical opinion. 23 Q. Read the conclusion, item two 24 of that medical opinion. Page 207 1 A. Now I'm a little confused. 2 That was the first letter of the BGA, you are 3 referring to the first letter of concerns of the 4 BGA? 5 Q. Yes. 6 A. This is the intent to reject. 7 Q. Yes, this is May, '84. 8 A. Yes, right, that was the 9 letter of concerns, and at this point in time 10 they made the statement, right. 11 Q. They made the statement 12 considering the benefit and the risk, we think 13 the preparation totally unsuitable for the 14 treatment of depression. 15 A. They made the statement in -- 16 yes. 17 Q. In May of when, 1984? 18 A. That was in '84, the first 19 letter which we received, the letter of concerns. 20 Q. And that's what this response 21 in September of '84 is in response to. 22 A. Yes, the response -- yes, 23 right, we responded to this letter, right. 24 Q. Exhibit 4. Page 208 1 A. Exhibit 4 was a draft of the 2 response. 3 Q. All right. So the same data 4 was analyzed by everyone, Lilly in Indianapolis, 5 originally? 6 A. Yes. 7 Q. I guess you assume they made 8 an analysis of that data to come to the 9 conclusion that it supported the conclusion that 10 it was safe and efficacious. 11 A. Yes, uh-huh. 12 Q. They submitted it to the BGA, 13 correct? 14 A. Correct. 15 Q. The BGA reviewed that data and 16 came to the conclusion it was totally 17 unacceptable for the treatment of depression. 18 A. They came to a different 19 conclusion, yes. 20 Q. Doctor Schenk reviewed that 21 data. 22 A. Yes. 23 Q. And concluded if the drug is 24 used according to the revised package literature, Page 209 1 i.e. in agitated and suicidal patients only 2 together with concomitant sedative drugs, there 3 should be no doubt on fluoxetine's positive 4 benefit/risk ratio in the treatment of 5 depression, correct? 6 A. Yes. 7 Q. Lilly's response was submitted 8 to the BGA. 9 A. Right. 10 Q. BGA came back with an opinion 11 or an intent to reject. 12 A. Yes. 13 Q. Whereby they expressed that -- 14 I want to quote it. The use of the preparation 15 seems objectionable as the increase in agitating 16 effect occurs earlier than the mood-elevating 17 effect, and therefore an increased risk of 18 suicide exists, correct? 19 A. Correct. 20 Q. According to the 21 intent-to-reject letter, you have the right to 22 withdraw your application. 23 A. Yes. 24 Q. And that's what was done. Page 210 1 A. No. 2 Q. What was done? 3 A. What was done was that we 4 objected to the letter, to the letter of the BGA. 5 Q. All right. And so what was 6 then submitted to the BGA? 7 A. Additional data. 8 Q. What additional data? 9 A. Wait a minute. First, we made 10 the objection and without any data, that was the 11 way to go, and the BGA accepted the objection, 12 provided that we give them additional reasons why 13 they should approve the drug, and that was done 14 then later. So I think they gave us time of 15 about three months and we much later provided 16 additional information because then we felt we 17 had to prepare additional data. 18 Q. Well -- 19 A. Additional studies, for 20 example. 21 Q. The first thing you did was 22 call in Doctor Herrmann to take a look at the 23 data, didn't you? 24 A. Right. Page 211 1 Q. And you had a meeting with 2 Doctor Herrmann, did you not? 3 A. Yes. 4 Q. Shortly after -- Doctor 5 Herrmann -- I want to let you just look at 6 Exhibit 6. 7 (PLAINTIFFS' EXHIBIT NO. 6 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 A. I'm aware of this letter, yes. 11 Q. Doctor Herrmann reviewed some 12 data, did he not? 13 A. Yes. 14 Q. Can you help us, Doctor Weber, 15 as to when Doctor Herrmann reviewed this data, do 16 you know? 17 A. End of March. The date of 18 April 29 and 30 was a mistake, it should have 19 read March 29 and 30. 20 Q. Well, is there anything else 21 that's a mistake on this document? 22 A. No, that is the only mistake. 23 Q. Why is there a mistake on the 24 date, do you have any explanation for that? Page 212 1 A. I think it was a typing error 2 or an error by the secretary. It says above that 3 the date of this telex was written in April 2, so 4 it is impossible then to report about a meeting 5 at April 29 and 30, so this is an obvious 6 mistake, a human mistake that happens from time 7 to time. 8 Q. Doctor Herrmann was called in 9 to give you advice so you'd be in a better 10 position in connection with the registration of 11 Prozac in Germany. 12 A. Yes. 13 Q. Who was his assistant? 14 A. His assistant was Johanna 15 Schenk -- well, his personal assistant was Doctor 16 Kurt Cowen, one of his employees, and at Lilly it 17 was Johanna Schenk primarily and the regulatory 18 people, as it asserted here, Frau Heymanns and 19 Frau Von Keitz. It is on the document. 20 Q. This document says that Doctor 21 Herrmann reviewed the original documentation 22 submitted March 1st, 1984, correct? 23 A. Yes. 24 Q. And he reviewed an analysis of Page 213 1 the pooled studies, fluoxetine versus imipramine 2 versus placebo, protocol number twenty-seven, 3 correct? 4 A. Yes. 5 Q. That's the Finer study that 6 you were talking about earlier? 7 A. Yes. 8 Q. And that he left an opinion of 9 twenty-one typewritten pages. 10 A. Yes. 11 Q. Who was the employee that was 12 there -- was Herrmann employed by Lilly? 13 A. No. 14 Q. Who was he working for? 15 A. He had -- he was head of a 16 contract research organization. 17 Q. What contract research 18 organization? 19 A. I think the name has changed 20 several times, but I think at this point of time 21 it was AFB. 22 Q. Do you know what AFB stands 23 for? 24 A. No, I don't know what it Page 214 1 stands for, but it's a contract research 2 organization for conducting clinical trials, 3 mainly for Phase 1 trials at this point of time. 4 Q. Phase 1 would be? 5 A. Early clinical trials, first 6 application to human beings. But not -- to avoid 7 a misunderstanding, he did not any study on this 8 fluoxetine at this point of time. 9 Q. Why was Doctor Schenk 10 assisting him? 11 A. Trying to give him the 12 information he was looking for. 13 Q. What information was he 14 looking for? 15 A. Well, I don't know because I 16 have not been at the meeting, but normally a 17 submission to the BGA is a huge document, and so 18 the BGA takes months to review it and in order to 19 retrieve, collect, select the important 20 documents, it would be necessary that regulatory 21 people or Johanna Schenk were going to assist 22 him. 23 Q. Okay. This just says that he 24 reviewed the original documentation submitted Page 215 1 March 1, 1984. 2 A. Yes. 3 Q. What was that, this huge body 4 of information that you're talking about? 5 A. Yes, everything was available 6 to him. 7 Q. All right. So I think you say 8 it's now March 29th and 30th, 1985, Doctor 9 Herrmann had before him everything that had been 10 submitted to the BGA? 11 A. Right. 12 Q. Including protocol number 13 twenty-seven? 14 A. Right. 15 Q. And he left an opinion of 16 twenty-one typewritten pages, correct? 17 A. Right. 18 Q. And that opinion deals with 19 efficacy and safety, does it not? 20 A. Yes. 21 Q. Doctor Schenk summarizes that 22 opinion, does she not? 23 A. Yes. 24 Q. She says under safety, the Page 216 1 seventh bullet point, still not resolved is the 2 fact that suicide attempts have been observed 3 more frequently on fluoxetine as compared to 4 imipramine. Only epidemiologic data or 5 literature on other antidepressants may help to 6 identify whether it happened by chance that 7 incidents of suicide attempts were abnormally 8 high on fluoxetine or abnormally low under 9 comparators, correct? 10 A. It says so, yes. 11 Q. Apparently it was Doctor 12 Herrmann's opinion that there was a negative 13 chance of approval by virtue of the increased 14 suicidal risk as based on his review of the 15 documents or of the data. 16 A. Well, suicidality was part of 17 it, yes. 18 Q. Well, he says -- it says, 19 according to today's knowledge, this is 20 negatively affected by the increased suicidal 21 risk, correct? 22 A. Where does it say so? 23 Q. Right under that fact where 24 he's talking about the suicide attempts Page 217 1 abnormally high on fluoxetine and abnormally low 2 on comparators. 3 A. He says this in respect to 4 adverse events, yes. 5 Q. That it's negatively affected 6 by the increased suicidal risk, correct? 7 A. Yes, uh-huh. 8 Q. And concludes under 9 probability of success that today's knowledge of 10 data does not justify the judgment that there is 11 a high probability of getting fluoxetine 12 registered in Germany, correct? 13 A. That is right, but it is not 14 only referring to suicidality and sides effects, 15 but also to efficacy. 16 Q. Okay. So his review said it 17 doesn't work, plus it's unsafe, right? 18 A. No, he didn't say that, but he 19 said that our data at this point of time is 20 probably not going to convince the BGA that this 21 would be -- that the benefit/risk situation would 22 be beneficial and that they were going to approve 23 the product. 24 Q. Because it hadn't shown any Page 218 1 efficacy and because it had shown some side 2 effects that were serious, correct? 3 A. No, he did not say this. He 4 said that the data which we presented are not 5 sufficient for the BGA. 6 Q. That data -- again, I want to 7 be clear. That data that he looked at is the 8 same data that had been looked at by the 9 investigators or the people in Indianapolis. 10 A. Right. 11 Q. And had been submitted to the 12 BGA. 13 A. Right. 14 Q. Had been looked at by Doctor 15 Schenk. 16 A. Yes. 17 Q. Had been rejected by the BGA. 18 A. Right. 19 Q. Then Doctor Herrmann, an 20 outside expert, comes in and says my review of 21 the same data is that we don't have any data to 22 support efficacy and the data suggests that 23 there's an increased risk of suicide, and that 24 the probability of a successful registration of Page 219 1 Prozac in Germany is low. 2 A. No, that is incorrect. He 3 said that the data which we have are not 4 sufficient for the BGA because the BGA is looking 5 for additional data such as, for example, data in 6 inpatients, which we have not done, and -- so 7 that in terms of efficacy, we certainly had data 8 that the drug was efficacious, but we had no data 9 in inpatients. And in terms of side effects, he 10 said that the concern of suicidality is still on, 11 we were not able to destroy this concern at this 12 point of time. 13 Q. And that the probability of 14 getting the product registered in Germany was 15 low. 16 A. It was low, especially to the 17 fact that he knew something which we have not 18 known at this point of time, that is that 19 inpatient data is very important for the approval 20 of antidepressants. 21 Q. How come you all didn't know 22 that? Just to put it in Texan. 23 A. We were inexperienced in the 24 requirements of antidepressants at this point of Page 220 1 time, the regulatory requirements. 2 Q. You thought that you had 3 sufficient studies to support efficacy. 4 A. Well, we felt that we had 5 sufficient studies and we still -- well, and 6 other regulatory bodies felt the same way, that 7 the data was sufficient, however the BGA was very 8 much focusing on inpatient data. We tried to 9 tell them that we have also patients of this 10 nature perhaps with severe depression, for 11 example, but they did not buy the argument and 12 thought we were arguing very hard that they 13 needed inpatients. That is of course a matter of 14 debate, inpatients important, yes or no. I don't 15 know some of the experts or the expert 16 psychiatrists in Germany felt it is not 17 important, others felt it might be appropriate 18 because it is a different type of setting a 19 patient is in, so it would be valid additional 20 information. 21 Q. Well, before you went to the 22 time and the effort to submit this product for 23 approval in Germany, didn't somebody make some 24 inquiry as to what would be necessary to Page 221 1 demonstrate efficacy in an antidepressant? 2 A. At this point of time, the 3 affiliate usually got involved very late in such 4 drug development processes. As a matter of fact, 5 all studies of fluoxetine have been done in the 6 United States which was also a matter of debate 7 at the BGA, and we got involved late, we did not 8 know about the importance of inpatients and that 9 was a deficiency on our side which will not 10 happen again. 11 Q. Was Aventyl on the market in 12 Germany at this time? 13 A. Which drug? 14 Q. Aventyl, Aventyl. 15 A. I think yes, uh-huh. 16 Q. Was Nortriptyline -- 17 A. Yes. 18 Q. -- manufactured and on the 19 market in Germany? 20 A. Nortriptyline was on the 21 market and still is on the market in Germany, 22 yes. 23 Q. Amitriptylene on the market in 24 Germany? Page 222 1 A. Yes. 2 Q. Nortriptyline on the market in 3 Germany? 4 A. Right. 5 Q. Fluvoxemine, was it on the 6 market in Germany? 7 A. I think not in '85, no. 8 Q. So there were other 9 antidepressants that had been approved in 10 Germany. 11 A. Yes, a large number of 12 antidepressants. 13 Q. Then how come you didn't know 14 about what should be done to get an 15 antidepressant registered in Germany? 16 A. Well, the importance of 17 inpatients did not come to our attention, mainly 18 because of the fact that most patients are 19 treated as outpatients anyway. It happened. 20 Q. Most patients in Germany are 21 treated as outpatients? 22 A. Yes. 23 Q. Isn't that -- couldn't that be 24 said -- be true everywhere -- Page 223 1 A. Yes. 2 Q. -- of depressed individuals? 3 A. Yes. 4 Q. Was there more clinical trials 5 done after Doctor Herrmann's review on the issue 6 of whether or not Prozac induced suicidality or 7 violent aggressive behavior? 8 MR. MYERS: I object to the form. He 9 didn't review violent or aggressive behavior, 10 there's no evidence of that. 11 MS. ZETTLER: Yes, there is. 12 MR. MYERS: Same objection. 13 A. I'm not aware of violent 14 behavior as a concern of the BGA, but in respect 15 to suicidality, no studies were done. We did 16 additional studies, but inpatient studies and 17 German outpatient studies. 18 Q. So there were more studies 19 done, weren't there? 20 A. Yes, yes. 21 Q. But none of those studies were 22 done to examine the issue of whether or not 23 Prozac caused suicidality, were they? 24 A. Suicidality is of course part Page 224 1 of every study, so a particular study, how to do 2 a particular study to analyze suicidality, no, 3 that was not done. 4 Q. Clinical trials that had been 5 done up to that time were not intended to assess 6 suicidality, were they? 7 MR. MYERS: Object to the form. Go 8 ahead, Doctor. 9 A. It was not a primary end 10 point. 11 Q. So after Doctor Herrmann made 12 his review, were there any studies that had the 13 primary end point? 14 A. Of suicidality? 15 Q. Yes. 16 A. No, but suicidality was 17 certainly collected in the data. 18 Q. Did anybody ever suggest that, 19 look, the German government has raised the issue 20 that this drug might cause suicidality? 21 A. Right. 22 Q. We've also been criticized 23 because we didn't do any inpatient studies in 24 connection with Prozac -- Page 225 1 A. Right. 2 Q. -- why don't we do an 3 inpatient study that examines the issue of 4 suicidality specifically, that way we'll get for 5 the German regulatory body not only data on 6 inpatient treated depressed people, but we'll 7 also get data on suicidality? 8 A. Well, I think the studies 9 which were conducted looked at efficacy and 10 safety, and suicidality is part of safety so we 11 looked of course at suicidality as -- 12 MR. MYERS: Let him finish, Paul, and 13 then -- go ahead, finish your answer. 14 A. No, I have looked at 15 suicidality as well. 16 Q. Why not look at suicidality 17 specifically since that was specifically a reason 18 that this product had been rejected in Germany? 19 A. I don't know what you mean by 20 specifically. How can you look at suicidality 21 other than in clinical trials and determine the 22 scales which are available in psychiatry which 23 has suicidal ideation, suicides and suicide 24 attempts, which of course we collect in every Page 226 1 study. 2 Q. Well, do you know whether or 3 not there were any scales used to measure 4 specifically whether or not patients were 5 becoming suicidal? 6 A. Yes, there were scales such as 7 suicidal ideation that were involved in every 8 study. 9 Q. Was I right -- 10 A. Yes. 11 Q. -- there was a suicidal 12 ideation scale -- 13 A. There is a -- 14 Q. -- employed in the clinical 15 trials? 16 A. There is suicidal ideation -- 17 there are suicidal ideation scales available. I 18 think -- again, I'm not an expert in the area, 19 but the scale which looks at depression includes 20 a subpoint which looks at suicidality, because 21 suicidality is such an important point of 22 depression that it is a matter of this scale. 23 Q. It is for your information, 24 Doctor Weber -- Page 227 1 A. Yes. 2 Q. -- one question as a part of 3 either a seventeen or twenty-one-question 4 depression scale, did you know that? 5 A. Excuse me, what did you say, 6 can you repeat that? 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED SECTION OF THE 9 DEPOSITION.) 10 A. That is what I just said, that 11 suicidality is part of such scales. 12 Q. Do you know of any scales 13 designed specifically to look exclusively at 14 suicidality? 15 A. No, I don't know. 16 Q. Do you know then whether or 17 not any of those scales were employed in any of 18 the clinical trials? 19 A. I left what is necessary to 20 study suicidality to the experts. 21 Q. Have you ever heard of Doctor 22 Stuart Montgomery? 23 A. Yes. 24 Q. Do you know whether or not he Page 228 1 did a study examining whether or not Prozac 2 reduced suicidality in individuals with 3 personality disorder? 4 A. Yes, I remember somewhat in 5 the back of my mind that he studied suicidality, 6 that is right. 7 Q. What were the results of that 8 study, Doctor Weber? 9 A. Well, I do not remember 10 exactly, but wasn't it that suicidal ideation was 11 reduced by fluoxetine? 12 Q. No. 13 A. Okay. Then tell me. 14 Q. It was that fluoxetine had no 15 effect as a prophylaxis for suicide. 16 MR. MYERS: Let me object to the form 17 of you telling the witness what the study showed. 18 MR. SMITH: He asked me and I was just 19 helping him. 20 MR. MYERS: I'm sure, you've been 21 trying to help him out all day. Go ahead and ask 22 him a question. 23 Q. Has anybody ever submitted to 24 you any type of report or data reflecting Doctor Page 229 1 Montgomery's study? 2 A. Well, I know that -- I know 3 about Doctor Montgomery's study, I do not 4 remember the details of the Doctor Montgomery 5 study. It did not occur to me so far in my 6 recollection that the study expressed any 7 difficulty with fluoxetine. 8 Q. What have you read, seen or 9 heard about the study? 10 A. What? 11 Q. What have you read, seen or 12 heard about the study? 13 A. It is somewhat long ago, I 14 don't remember. But if there would be an issue 15 regarding suicidality, I would know. I do not 16 remember that there was any issue. 17 Q. Did you know that the study 18 was designed to examine aspects of suicidality 19 specifically? 20 A. I do not know this. 21 Q. So what was Professor 22 Herrmann's conclusions on whether or not this 23 Prozac was related to suicidality? 24 MR. MYERS: At what point in time? Page 230 1 MR. SMITH: Well, at any point in 2 time. 3 A. See, I think he said that the 4 suicidality point is not clear at this point of 5 time because we had patients -- suicides under 6 fluoxetine and maybe the number was higher in 7 those of the control groups and we need to 8 clarify this question, this was his advice. 9 Q. How did he suggest that be 10 done? 11 A. He -- I do not recall what he 12 recommended. What I recall that a number of 13 things were recommended, maybe by him, maybe by 14 other experts. For example look at the time when 15 the suicide was -- the suicide attempt was 16 committed, looking at the suicide reports in 17 detail, looking at -- well, that is what I 18 remember. 19 Q. Did he ever change his 20 conclusion or come up with an opinion? 21 A. I think he changed his 22 conclusion based upon an expert opinion. 23 Q. I thought he was the expert. 24 A. Who? Page 231 1 Q. I thought he was the expert. 2 A. Not on suicidality 3 particularly. He was an expert on the whole 4 documentation, including efficacy and safety, but 5 not on suicidality particularly. 6 Q. Who was the expert on 7 suicidality? 8 A. That was -- we had two experts 9 to look at suicidality, Professor Vincent Leet 10 and Paul Meyer. 11 MR. SMITH: Let's take a quick break. 12 (A SHORT RECESS WAS TAKEN.) 13 Q. (BY MR. SMITH) Doctor Weber, 14 would you look at Exhibit 3, which is the medical 15 statement, the list of concerns. Do you have 16 that before you? 17 A. Yes. 18 Q. That was the BGA document that 19 was the medical criticism originally leveled 20 against Prozac, was it not? 21 A. Yes, that's right. 22 Q. When did you go back -- when 23 did you come back to the United States, in 1987? 24 A. When I came to the United Page 232 1 States to work here as an employee, that was in 2 '87, right. 3 Q. When in '87? 4 A. In September, around 5 September. 6 Q. You know Doctor Max Talbott 7 then? 8 A. Yes. 9 Q. Head of regulatory affairs -- 10 A. Yes, I know him. 11 Q. -- in the United States? 12 A. Yes. 13 (PLAINTIFFS' EXHIBIT NO. 7 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 Q. You've probably not seen that 17 document, and in the interest of time I'm going 18 to try to walk you through it. If you look at 19 the first page, you'll see it's dated -- that 20 it's a letter from Lilly Research Laboratories. 21 A. Yes. 22 Q. From Doctor Talbott to the 23 United States Food and Drug Administration. 24 A. Yes. Page 233 1 Q. And it's dated October 26, 2 1987. 3 A. That's right. 4 Q. And he's reporting it appears 5 to the United States Food and Drug Administration -- 6 A. Yes. 7 Q. -- on what has occurred in 8 connection with the approval process of Prozac in 9 countries outside of the United States, correct? 10 A. Okay, uh-huh. 11 Q. Does that appear correct? 12 A. Yes, that's correct. 13 Q. And that has to do with what 14 has occurred over the years in connection with 15 the approval process of Prozac in other 16 countries, correct? 17 A. I think so, yes. 18 Q. Turn to page Pz 2027 1648. 19 A. Okay. 20 Q. It says BGA German regulatory 21 correspondence, does it not? 22 A. Uh-huh. 23 Q. And that document outlines 24 what has occurred in Germany, correct? Page 234 1 A. Yes. 2 Q. And it -- did you and he 3 discuss anything that had occurred in Germany up 4 to that point? 5 A. After that point? 6 Q. Up to October of 1987. 7 A. After October? 8 Q. Up to. 9 MS. ZETTLER: Up until that point, 10 Doctor. 11 A. Oh, up to this point. I do 12 not know exactly. Again, it's a long time ago, 13 but he may have shared this document with me, 14 might be an opportunity. 15 Q. And he's listing there that 16 the BGA responded in May, 1984 with a letter of 17 concerns, is he not? 18 A. Yes, uh-huh. 19 Q. And you have that BGA May, 20 1984 letter of concerns right in front of you, 21 don't you? 22 A. Yes. 23 Q. All right. Let's go -- let's 24 compare what he says -- Page 235 1 A. All right. 2 Q. -- and what the BGA letter of 3 concern says, right? 4 A. Yes, okay. 5 Q. Item -- I'm trying to find it 6 and I'm trying to hurry -- eighteen of Doctor 7 Talbott's report to the United States Food and 8 Drug Administration says that the BGA in 1980 -- 9 in May, 1984 stated, quote, eighteen, please 10 provide an in-depth analysis of suicides and 11 suicide attempts patient-by-patient, timing, 12 symptomatology at trial entry, phase of trial and 13 any other clinical relevant comments, correct? 14 A. Yes. 15 Q. But actually, in May of 1984 16 what the medical concern was was, quote -- look 17 at Exhibit 3 -- 18 A. Yes. 19 Q. -- on page 1525. 20 A. Right. 21 Q. During the treatment with the 22 preparation, sixteen suicide attempts were made, 23 two of these with success. As patients with the 24 risk of suicide were excluded from the studies, Page 236 1 it is probable that this high proportion can be 2 attributed to an action of the preparation in the 3 essence of a deterioration of the clinical 4 condition which reached its lowest point, 5 correct? 6 A. Yes. 7 Q. So those -- Doctor Talbott did 8 not accurately state what the BGA stated in May, 9 1984, did he, to the United States Food and Drug 10 Administration? 11 A. He did not translate it 12 word-by-word, no. 13 Q. He didn't even quote it in 14 English word-by-word, did he? 15 A. I think what he did was an 16 interpretation of what is important to write back 17 to the BGA, yes. 18 Q. Well, he didn't say that there 19 were sixteen suicide attempts, did he? 20 A. No. 21 Q. He didn't say that patients 22 from -- with suicidal risk were excluded from the 23 trial, clinical trials, did he? 24 A. No. Page 237 1 Q. He didn't say that the British 2 medical opinion -- I mean that the German medical 3 opinion was that it was probable that this high 4 proportion can be attributable to the action of 5 the preparation, did he? 6 A. He did not say this, no. 7 Q. He didn't advise the Food and 8 Drug Administration that in their summary on page 9 four they had concluded that considering the 10 benefit and the risk, we think this preparation 11 totally unsuitable for the treatment of 12 depression, did he? 13 A. I cannot find it right now. 14 Q. Take a second and look. You 15 don't see it in this twenty items that he 16 mentions, do you? 17 A. No. 18 Q. Look back on page fifteen 19 twenty-five of the BGA medical opinion. 20 A. Okay. 21 Q. Their list of concerns. 22 A. Right. 23 Q. Also turn to item thirteen of 24 what Doctor Talbott is telling the United States Page 238 1 Food and Drug Administration concerning side 2 effects. 3 A. Yes. 4 Q. He tells the U.S. FDA that the 5 German medical opinion said please explain the 6 high frequency of side effects, ninety percent, 7 in terms of dose, age and duration of therapy. 8 Also provide side effect severity data. That's 9 what he says that the medical opinion to the BGA 10 raised. 11 A. Yes. 12 Q. Isn't he? 13 A. Yes. 14 Q. But actually what it says on 15 the top paragraph there of what the BGA medical 16 opinion actually was was, quote, the frequency of 17 side effects was very high, partly more than 18 ninety percent, and the side effects resulted 19 nearly in each study in dropouts. The frequency 20 of sides effects depended on the dose, the age 21 and the duration of therapy. Deciding for the 22 clinical significance of side effects is not only 23 their frequency of their occurrence, but also 24 their severity. Page 239 1 A. Uh-huh. 2 Q. Correct? 3 A. Yes. 4 Q. So in item thirteen, he 5 doesn't accurately state what the medical opinion 6 of the BGA was, does he? 7 A. He did not express it the same 8 way as the BGA stated it. 9 Q. The BGA stated it in a manner 10 much more critical of Prozac than did Doctor 11 Talbott in reporting to the FDA. 12 A. Well, he mentioned what the 13 questions were in respect to number thirteen. 14 Q. In fact it wasn't a question, 15 was it, it was a statement by the BGA? 16 A. It's what the concerns were, 17 yes. 18 Q. He didn't say that the BGA 19 said that the frequency and the severity of the 20 side effects was a concern. 21 A. But he at least mentioned 22 severity. 23 Q. Well, he says provide side 24 effect severity data, where the BGA was actually Page 240 1 saying the frequency of the occurrence but also 2 their side effects was clinically significant to 3 the BGA. 4 MR. MYERS: You cut him off again, 5 Paul. Doctor, finish your earlier question if 6 you were not through, and then answer Mr. Smith's 7 question. 8 MS. ZETTLER: I think he was done, 9 Larry. 10 MR. MYERS: He was still talking, 11 Nancy. 12 THE WITNESS: I think I was done. 13 MR. MYERS: All right. 14 Q. Can you answer my question, do 15 you need me to ask it again? 16 A. Yes, I'm a little bit -- let 17 me perhaps say that the time when this was done 18 was later than this, and this was obviously done 19 after we already received the second letter of 20 the BGA. So he obviously focused more on the 21 second letter than the first one. 22 Q. This is all on the May, 1984. 23 A. Yes. I don't know why it was 24 written this way. I can only speculate Page 241 1 addressing it that it would be concerns to the 2 BGA because of what was stated in the letter of 3 concerns, and he abbreviated the points. 4 Q. He abbreviated the points at 5 best, correct? 6 A. He -- yes. 7 Q. And he didn't give as much 8 information to the United States Food and Drug 9 Administration as was actually imparted by the 10 medical opinion of the BGA, did he? 11 A. Perhaps he tried to make it 12 more digestable. 13 Q. Perhaps he tried to make it 14 more confusing and obscure, correct? 15 MR. MYERS: Let me object to the form. 16 Go ahead, Doctor. Can you answer it? 17 A. Well, I think he made it 18 abbreviated that the FDA -- to make it easier to 19 the FDA. But you may be right that he stated not 20 the concerns of the BGA in the same way as it was 21 made by the BGA. 22 Q. And in as strong a manner, 23 correct, in all honesty? 24 A. Well, in terms of point Page 242 1 eighteen, I would agree, yes. 2 Q. And point eighteen has to do 3 with suicide, doesn't it? 4 A. Yes. 5 Q. And he never told them what 6 the conclusion of the May, 1984 medical opinion 7 was, did he? 8 A. No. 9 Q. Do you see anywhere there in 10 Doctor Talbott's letter to the United States Food 11 and Drug Administration that he advised them that 12 in May, 1984 the BGA had concluded that 13 considering the benefit and the risk, we think 14 the preparation totally unsuitable for the 15 treatment of depression? 16 A. I have not read the whole 17 document, but -- 18 MR. MYERS: Doctor, if you need to 19 read the whole document to answer the question, 20 read the whole document. 21 A. Well, I would say it should 22 have been here on point twenty in the additional 23 questions. 24 Q. And it's not, is it? Page 243 1 A. No. He focused more on the 2 second letter of the BGA as the letter -- the 3 intent of rejections, which was more relevant at 4 this point of time. 5 Q. Well, did you not consider it 6 relevant, Doctor Weber, in Germany that the BGA 7 had made a determination, a medical determination 8 that Prozac was totally unsuitable for the 9 treatment of depression considering the benefit 10 and the risk? 11 A. Yes, it was. But at this 12 point of time, the second letter of intent was 13 much more relevant for us because it was the 14 actual state of the discussion. 15 Q. Well, the second letter of 16 intent indicates that there was unacceptable 17 damaging effect, doesn't it? 18 A. The second letter? 19 Q. Point two. 20 A. Point two. What it says is 21 that they have unacceptable damaging effects. 22 Q. It says for the drug's concern 23 there is according to their specific profile of 24 adverse effects, the justified suspicion that Page 244 1 they have unacceptable damaging effects. 2 A. That's right. 3 Q. What were those unacceptable 4 damaging effects, Doctor Weber? 5 A. That is specified in the 6 points -- after point two, in two point one, two 7 point two and two point three. 8 Q. So two point one, two and 9 three are outlining what specific unacceptable 10 damaging effects there were, is that correct? 11 A. That is as I understand the 12 letter. 13 Q. The use of the preparation 14 seems objectionable as the increasing in 15 agitating effect occurs earlier than the 16 mood-elevating effect, and therefore an increased 17 risk of suicide exists. 18 A. Yes. He used here the 19 specific wording of the BGA. 20 Q. He uses the specific wording 21 of the BGA there -- 22 A. Right. 23 Q. -- but he didn't in talking 24 about the May, 1984 list of medical concerns that Page 245 1 you had received, did he? 2 A. No, he abbreviated this, yes. 3 Q. And he abbreviated in a manner 4 that didn't indicate fully in connection with 5 suicide what the medical concern was, correct? 6 MR. MYERS: Object to the form. Go 7 ahead, Doctor, and answer. 8 A. That is correct. 9 Q. In other words, the medical 10 concern in Germany as expressed in May of 1984 11 was that there were sixteen suicides, that 12 suicide risk was excluded from the clinical 13 trials and therefore the high proportion can be 14 attributed to the action of the preparation, 15 right? 16 A. Yes, that is right. 17 Q. And Doctor Talbott never 18 reported that to the United States Food and Drug 19 Administration, did he? 20 A. He did not in this letter. I 21 do not know what is all about this letter, I 22 think what it should say probably is what is the 23 status at this point in time, and at this point 24 in time the second question was much more Page 246 1 relevant than the first one. But what you said 2 is correct. 3 Q. But you never talked with 4 Doctor Weber that you can recall about the fact 5 that he was going to be -- Doctor Talbott that he 6 was going to be reporting to the FDA concerning 7 these German regulatory matters. 8 A. I'm not absolutely sure. At 9 this point of time I was not in Germany. He 10 could have done this with the help of the German 11 affiliate or on the basis of the documents which 12 he has available. He may have talked to me about 13 this letter, but I do not recall. 14 Q. When you came to the United 15 States in 1987, did you become aware that the 16 United States Food and Drug Administration was 17 interested in what foreign regulatory bodies had 18 done in connection with Prozac? 19 A. I think I was aware about 20 this, yes. 21 Q. What's your understanding as 22 to why they were interested in what foreign 23 regulatory -- why the FDA was interested in what 24 say for instance the BGA had done in connection Page 247 1 with Prozac? 2 A. I do not exactly understand 3 the regulatory requirements of the United States, 4 but they obviously take this into review what is 5 the status in other countries. 6 Q. Probably because -- well, 7 wouldn't it be legitimate -- a legitimate 8 assumption that the United States Food and Drug 9 Administration considers what other scientists 10 might have to say about the drug in other parts 11 of the world as being significant in connection 12 with the safety and efficacy of Prozac? 13 MR. MYERS: Object to the form. Go 14 ahead. 15 A. It would be speculative on my 16 side because I am not familiar with the 17 requirements. 18 (DISCUSSION OFF THE RECORD.) 19 (PLAINTIFFS' EXHIBIT NO. 8 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 Q. (BY MR. SMITH) Look at 23 paragraph five. 24 A. Paragraph five? Page 248 1 Q. Yes, sir. What does paragraph 2 five say? 3 A. Require review of status of 4 all fluoxetine actions taken or pending before 5 foreign regulatory authorities. Approval actions 6 can be noted, but we ask that you describe in 7 detail any and all actions taken that have been 8 negative, supplying a full explanation of the 9 views of all parties and the resolution of the 10 matter. 11 Q. It says describe in detail, 12 doesn't it? 13 A. Yes. 14 Q. It says a full explanation of 15 all views of all parties, doesn't it? 16 A. Yes, uh-huh. 17 Q. Turn to the front page of that 18 document. 19 A. The front page, yes, okay. It 20 is addressed to Doctor Talbott from the 21 Department of Health and Human Services. 22 Q. The FDA, right? 23 A. Yes. 24 Q. What does it say in connection Page 249 1 with their intent to do in connection with the 2 application for Prozac in the United States? 3 A. That they would like to have 4 information about the status -- of the regulatory 5 status in other countries. 6 Q. Does the BGA request 7 information concerning regulatory status of a 8 product under review for their process? 9 A. That can happen, yes. 10 Q. In other words, have you seen 11 as medical director in Germany requests from the 12 BGA that you, the German affiliate, advise them 13 as to the regulatory status of a product in other 14 countries, such as the United States? 15 A. No, no, they didn't -- not in 16 such specific terms, no, no. 17 Q. Generally do you know whether 18 or not you try to make the BGA knowledgable 19 concerning the regulatory status of products of 20 Lilly world wide? 21 A. No, that is not the intent we 22 have. Each regulatory body is obviously 23 different and I think we deal with the BGA 24 questions, and they're obviously less interested Page 250 1 in what is going on in other countries than it 2 occurs to me as the FDA. 3 MS. ZETTLER: I'm sorry, did you say 4 that the BGA is not as interested in what goes on 5 in other countries as the FDA is? 6 THE WITNESS: They do not ask this 7 specific questions, but they ask that all data be 8 submitted to them. 9 Q. Is the Commission A procedure 10 that's used in Germany a procedure that's 11 designed to ensure safety and efficacy of drug 12 products in Germany? 13 A. Is the Commission A designed 14 to consider safety and efficacy? 15 Q. My question stems from the 16 fact that Commission A seems to me like an 17 additional body -- 18 A. Yes. 19 Q. -- in Germany -- 20 A. Right. 21 Q. -- that reviews safety and 22 efficacy of products. 23 A. Yes. 24 Q. Is the purpose of having a Page 251 1 Commission A to better ensure that safe and 2 efficacious products are provided to the 3 individuals living in Germany? 4 A. I think that is true, yes. 5 Q. It's just an additional 6 safeguard so to speak. 7 A. Yes, I would - yes. 8 Q. Do you think it's effective 9 generally as an additional safeguard? 10 A. I think it is effective 11 because there are other experts' opinions who can 12 raise questions and those sort of things. 13 Q. But it's a good concept at 14 least? 15 A. I think it is a good concept, 16 yes. 17 (PLAINTIFFS' EXHIBIT NO. 9 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Exhibit 9 is a letter dated 21 August 23, 1989 from Mr. Claude Bouchy, is it 22 not? 23 A. Uh-huh. 24 Q. And it talks about the review Page 252 1 of Commission A in August of '89, correct? 2 A. Yes. 3 Q. It says fluoxetine was 4 discussed in Commission A on August 21st as 5 planned, and this is what I have been able to 6 learn from several sources. 7 A. Uh-huh. 8 Q. Correct? 9 A. Yes. 10 Q. Now the discussions -- actual 11 discussions in Commission A are supposed to be 12 confidential, aren't they? 13 A. Yes. 14 Q. And pharmaceutical 15 manufacturers are not supposed to know what's 16 going on there, is it? 17 A. Yes. 18 Q. And this letter goes on to say 19 on the issue of the indication, the proposal of 20 Doctor Karkos, the BGA reviewer, to have 21 fluoxetine reserved when the treatment with other 22 antidepressants was unsuccessful and when no 23 sedation is required was strongly and apparently 24 successfully challenged by the reporter, Page 253 1 Professor Moeller and Professor Kleinsorge. Both 2 had been contacted directly and indirectly by us, 3 and based on what I heard through Straeter and 4 Lode, the Commission A voted in the end that 5 fluoxetine be indicated for the treatment of 6 depression, end quote, correct? 7 A. Yes. 8 Q. Were you back in Germany when 9 this occurred? 10 A. No. 11 Q. You were still here in the 12 United States? 13 A. I was still in the United 14 States. 15 Q. Did you know this was going 16 on, Doctor Weber? 17 A. No, I did not know. 18 Q. Would you approve of this, 19 Doctor Weber? 20 A. I do not know what happened, 21 actually. 22 Q. What you read, do you approve 23 of that frankly? 24 A. I think that is very difficult Page 254 1 for me to judge without knowing the 2 circumstances, and I do not know any of the 3 circumstances. 4 Q. Based on what you see, do you 5 approve of that, Doctor Weber? 6 MR. MYERS: Object to the question, 7 he's answered it twice, Paul. Go ahead, Doctor, 8 answer it one more time. 9 A. I don't know when -- Professor 10 Moeller and Professor Kleinsorge could have been 11 approached at one point of time, it depends a 12 little bit on the timing. And about what they 13 were approached, I cannot tell you, I need to 14 know the circumstances. 15 Q. What's written here says both 16 had been contacted directly and indirectly, 17 doesn't it? 18 A. Yes. I not know what it 19 means, directly and indirectly, I need you ask 20 the person to learn what. 21 Q. It says by us that they have 22 been contacted directly and indirectly, doesn't 23 it? 24 A. Yes, but not by me. Page 255 1 Q. I understand that. This whole 2 document is marked strictly confidential, isn't 3 it? 4 A. That is -- said strictly 5 confidential, yes. 6 Q. Do you take it from reading 7 this that Doctor Karkos wanted to limit Prozac 8 for use only when other antidepressant treatment 9 had failed or was unsuccessful and when no 10 sedation was required? 11 A. I read this here. 12 Q. That way, do you read it that 13 way like I just stated? 14 A. Yes, yes. 15 Q. Had you heard that Doctor 16 Karkos was recommending Prozac be limited in this 17 way? 18 A. No, I have not heard about 19 that. 20 Q. Who is Lode that's mentioned 21 here? 22 A. Lode is also -- Lode is an 23 expert in infectious diseases who also -- I'm not 24 sure whether he was a Commission A member at this Page 256 1 time, but he is -- I think he is today. 2 Q. Lode's on the commission now, 3 for sure. 4 A. Lode is one of the -- is one 5 of the replacements on the commission, yes. 6 Q. Was Straeter Lilly's lawyer at 7 this time, in August, 1989? 8 A. Yes, I think so, yes, he has 9 been. 10 Q. How would Straeter know what 11 was going on inside Commission A? 12 A. I don't know. 13 Q. Look with me in the last 14 paragraph on that first page, the middle of the 15 sentence -- or middle of the paragraph. 16 A. Yes. 17 Q. It says in the past there have 18 been very few cases where the BGA has made 19 decisions against the recommendation of the 20 Commission A, and we clearly have here a case 21 where the BGA reviewer has been voted down by 22 Commission A, right? 23 A. That is said, yes. 24 Q. The paragraph goes on to say Page 257 1 later on in the paragraph, this leads us to still 2 believe that we will get an acceptable 3 registration in the coming months, correct? 4 A. Yes, uh-huh. 5 Q. Professor Moeller has done 6 clinical trials for Lilly, hasn't he? 7 A. I'm not sure whether he has 8 done clinical trials up to this time. He's doing 9 clinical trials now for us, he has not done 10 clinical trials until I left the country. 11 Q. But he is now -- 12 A. Yes. 13 Q. -- employed by Lilly? 14 A. No, no, Professor Moeller is 15 not employed by Lilly, he is an independent 16 psychiatrist who does clinical trials from time 17 to time for us. 18 Q. And he's paid by Lilly to do 19 those trials. 20 A. For conducting clinical trials 21 as an investigator, yes. 22 Q. Yes. 23 A. Right. 24 Q. Professor Moeller gets a check Page 258 1 in some form from Eli Lilly and Company, doesn't 2 he? 3 A. For the clinical trials he is 4 conducting, yes, that is right. 5 Q. Has Doctor Lode -- was 6 Professor Moeller ever an expert hired by Lilly? 7 A. Not I think in connection with 8 approval of fluoxetine as far as I'm aware of, at 9 least not until I have left the country. In the 10 meantime he is -- we call him frequently as an 11 advisor because he is -- actually he's a leading 12 psychiatrist in Germany. So his advice is very 13 important. 14 Q. But he's on Commission A, 15 correct? 16 A. I think he's the replacement 17 for Benkert, but I'm not sure. 18 Q. And there are not supposed to 19 be any contact by members of Commission A with 20 the pharmaceutical industry? 21 A. But I don't know whether he at 22 this point in time was a member of Commission A, 23 I cannot tell it to you he is now. 24 Q. Obviously he was a member then Page 259 1 because it says that Doctor -- on the issue of 2 the indication, the proposal of Doctor Karkos, 3 the BGA reviewer, to have fluoxetine reserved 4 when the treatment with other antidepressants was 5 unsuccessful and when no sedation was required 6 was strongly and apparently successfully 7 challenged by the reporter, Professor Moeller and 8 Professor Kleinsorge? 9 A. You're obviously right, he was 10 on Commission A at this point in time. 11 Q. And now he's an expert for 12 you, now he's an expert for you? 13 A. Yes. 14 MR. SMITH: That's all we have, Doctor 15 Weber. 16 MR. MYERS: No questions. 17 (THE WITNESS WAS EXCUSED.) Page 260 1 COMMONWEALTH OF KENTUCKY ) 2 : ss COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 DOCTOR HANS WEBER 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 24TH DAY OF 19 SEPTEMBER, 1994. 20 MY COMMISSION EXPIRES MARCH 10, 1994. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 261 1 E R R A T A S H E E T 2 3 STATE OF ) : SS 4 COUNTY OF ) 5 6 I, DR. HANS WEBER, THE UNDERSIGNED 7 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 8 OF MY DEPOSITION AND WITH THE CHANGES NOTED 9 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 10 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 11 THE 10TH DAY OF SEPTEMBER, 1994 AT THE TIME AND 12 PLACE STATED THEREIN. 13 PAGE NO. LINE NO. CHANGE REASON Page 262 1 PAGE NO. LINE NO. CHANGE REASON 2 3 4 5 6 7 8 _____________________________ 9 DR. HANS WEBER 10 SWORN TO AND SUBSCRIBED BEFORE ME THIS 11 _____ DAY OF __________, 1994. 12 _____________________________ NOTARY PUBLIC, STATE OF 13 AT LARGE Page 263 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Page 264 1 BY MR. SMITH:.....................................12 2 COMMONWEALTH.....................................261 3 PLAINTIFFS' EXHIBIT NO. 1........................105 4 PLAINTIFFS' EXHIBIT NO. 2........................121 5 PLAINTIFFS' EXHIBIT NO. 3........................132 6 PLAINTIFFS' EXHIBIT NO. 4........................144 7 PLAINTIFFS' EXHIBIT NO. 5........................197 8 PLAINTIFFS' EXHIBIT NO. 6........................212 9 PLAINTIFFS' EXHIBIT NO. 7........................233 10 PLAINTIFFS' EXHIBIT NO. 8........................248 11 PLAINTIFFS' EXHIBIT NO. 9........................252 12 13 14 15 16 17 18 Page 265