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: EARLENE ASHBROOK 11 DATE: DECEMBER 9 AND 10, 1993 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 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 SUPERIOR COURT OF THE STATE OF CALIFORNIA 14 FOR THE COUNTY OF LOS ANGELES 15 DR. MARIUS SAINES, etc., et al., ) Case No: 16 ) SC 008331 Plaintiffs, ) 17 ) vs. ) 18 ) ELI LILLY & COMPANY, a corporation; ) 19 DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1- ) 20 100, inclusive, ) ) 21 Defendants. ) ____________________________________) 22 23 * * * * * * * * * * Page 2 1 THE DEPOSITION OF EARLENE ASHBROOK TAKEN AT 2 THE OFFICE OF BAKER & DANIELS, 300 NORTH MERIDIAN 3 STREET, SUITE 2700, INDIANAPOLIS, INDIANA 46204, 4 ON DECEMBER 9 AND 10, 1993; 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 NANCY ZETTLER 10 COUNSEL FOR PLAINTIFFS LEONARD M. RING AND ASSOCIATES, P.C. 11 111 WEST WASHINGTON AVENUE, SUITE 1333 CHICAGO, ILLINOIS 60602 12 LAWRENCE J. MYERS 13 COUNSEL FOR ELI LILLY AND COMPANY FREEMAN & HAWKINS 14 4000 ONE PEACHTREE CENTER 303 PEACHTREE STREET, N.E. 15 ATLANTA, GEORGIA 30308-3243 16 MARGARET M. HUFF ELI LILLY AND COMPANY 17 LILLY CORPORATE CENTER INDIANAPOLIS, INDIANA 46285 18 BENJAMIN E. PATTERSON 19 COUNSEL FOR DEFENDANTS CZECHOWICZ, FINK, BRUINSMA CLAUSEN MILLER GORMAN CAFFREY & WITOUS 20 10 SOUTH LASALLE CHICAGO, ILLINOIS 60603 21 PAUL SMITH 22 COUNSEL FOR PLAINTIFFS 745 CAMPBELL CENTER 2 23 8115 NORTH CENTRAL EXPRESSWAY DALLAS, TEXAS 75206 Page 3 1 I N D E X 2 3 DEPOSITION OF EARLENE ASHBROOK 4 5 DIRECT EXAMINATION BY MR. SMITH 5 6 CROSS EXAMINATION BY MS. ZETTLER 306 7 CERTIFICATE 465 8 ERRATA 466 9 10 EXHIBITS 11 PLAINTIFFS' EXHIBIT NO. 1 172 12 PLAINTIFFS' EXHIBIT NO. 2 180 PLAINTIFFS' EXHIBIT NO. 3 186 13 PLAINTIFFS' EXHIBIT NO. 4 196 PLAINTIFFS' EXHIBIT NO. 5 287 14 PLAINTIFFS' EXHIBIT NO. 6 303 PLAINTIFFS' EXHIBIT NO. 7 328 15 PLAINTIFFS' EXHIBIT NO. 8 331 PLAINTIFFS' EXHIBIT NO. 9 353 16 PLAINTIFFS' EXHIBIT NO. 10 358 PLAINTIFFS' EXHIBIT NO. 11 366 17 PLAINTIFFS' EXHIBIT NO. 12 384 PLAINTIFFS' EXHIBIT NO. 13 391 18 PLAINTIFFS' EXHIBIT NO. 14 409 PLAINTIFFS' EXHIBIT NO. 15 425 19 PLAINTIFFS' EXHIBIT NO. 16 441 Page 4 1 2 COMES EARLENE ASHBROOK, CALLED BY THE 3 PLAINTIFFs, AND AFTER FIRST BEING DULY SWORN, WAS 4 DEPOSED AND TESTIFIED AS FOLLOWS: 5 DIRECT EXAMINATION 6 BY MR. SMITH: 7 Q. Would you state your name, 8 please, Ma'am? 9 A. Earlene Ashbrook. 10 Q. How old a lady are you? 11 A. I'm sorry, what did you -- 12 Q. How old a lady are you? 13 A. Forty-eight. 14 Q. I'm starting off by being 15 offensive. Are you married? 16 A. Divorced. 17 Q. What was your former husband's 18 name? The reason I ask that, and I'm not trying 19 to be personal, but I think I saw some document 20 with another Ashbrook on there, and I want -- it 21 was Charles Ashbrook or something of that nature. 22 A. Yes. 23 Q. Are you any kin to Mister 24 Charles Ashbrook? Page 5 1 A. I was. 2 Q. When were you and Mister 3 Ashbrook married and when were you divorced? 4 A. We were married in 1970, 5 divorced in 1991. 6 Q. Do you have children? 7 A. Yes. 8 Q. How many? 9 A. One. 10 Q. Is it Doctor Charles Ashbrook? 11 A. No. 12 Q. Charles Ashbrook was an 13 employee of Lilly? 14 A. Yes. 15 Q. What was his -- is he still 16 employed by Lilly? 17 A. Yes. 18 Q. What is his current position 19 with Lilly? 20 A. He's in the patent division. 21 Q. Is he an attorney? 22 A. Yes. 23 Q. Since he's been with Lilly, 24 has he been in the patent division? Page 6 1 A. No. 2 Q. What other jobs has he had 3 with Lilly? 4 A. He has had several different 5 jobs. Started out right out of high school 6 working on a line, working on a line, 7 manufacturing line. 8 Q. Okay. What other jobs? 9 A. Worked in research. 10 Q. What did he do in research? 11 A. Well, he was a technician 12 while he was going to school, then he was a 13 chemist. 14 Q. All right. 15 A. Then he went to law school. 16 Q. Did he go to law school with 17 Doctor Stark? 18 A. I don't know. 19 Q. Paul Stark, you know Paul 20 Stark? 21 A. I know him. 22 Q. You know he's got a law 23 degree, don't you? 24 A. If you say so, I mean I think Page 7 1 maybe I've heard that. 2 Q. He's never practiced. 3 A. Okay. 4 Q. When was he in law school, 5 Mister Charles Ashbrook? 6 A. In the '70's, graduated in 7 '79. 8 Q. Then what did he do at Lilly? 9 A. He's been in the patent 10 division. 11 Q. When he was a chemist, what 12 was his area of expertise? 13 A. I don't know. 14 Q. When did you meet him? 15 A. '68. 16 Q. And he was working for Lilly 17 at that time? 18 A. Yes. 19 Q. Were you working for Lilly at 20 that time? 21 A. Yes. 22 Q. What was his job with Lilly at 23 that time? 24 A. He was a technician at that Page 8 1 time. 2 Q. In the research division? 3 A. Yes. 4 Q. And what was your position at 5 that time? 6 A. I was a chemist. 7 Q. What degrees does Mister 8 Charles Ashbrook have other than a law degree? 9 A. Bachelor's degree and Master's 10 degree. 11 Q. Bachelor's and Master's in 12 what, please, Ma'am? 13 A. I don't recall what his 14 Bachelor's degree was in, I think it was 15 chemistry. His Master's degree is in organic 16 chemistry. 17 Q. Did he ever work -- did 18 Charles Ashbrook ever do any work on Fluoxetine? 19 A. I don't know. 20 Q. Do you know whether or not he 21 did any work with respect to any research on a 22 specific serotonin reuptake inhibitor? 23 A. I don't know. 24 Q. Do you know whether or not he Page 9 1 did any research into any 2 neuropsychopharmacological drugs? 3 A. I don't know. 4 Q. What is your understanding 5 with respect to the type of research he did? 6 A. We never discussed it. 7 Q. But as far as you know, your 8 former husband, Charles Ashbrook, never did any 9 work in connection with Fluoxetine? 10 A. Not that I'm aware of. 11 Q. When he was a chemist and 12 doing research, do you know what products he was 13 working on? 14 A. I don't. 15 Q. Or what compounds he was 16 researching? 17 A. I don't. 18 Q. Do you know even the area? 19 A. I don't. 20 Q. Give me your educational 21 background, Ms. Ashbrook? 22 A. I have a Bachelor's degree in 23 education with a major in chemistry and minor in 24 biology. I have a Master's degree in organic Page 10 1 chemistry. 2 Q. When did you graduate from 3 high school, and where, please, Ma'am? 4 A. From high school, Meadowdale 5 in Dayton, Ohio in 1963. 6 Q. And where did you get your 7 Bachelor's degree? 8 A. Bowling Green State 9 University, Bowling Green, Ohio. 10 Q. When, please? 11 A. 1967. 12 Q. And when did you get your 13 Master's? 14 A. In 1971. 15 Q. From where? 16 A. IUPUI. 17 Q. What is IU -- 18 A. Indiana University, Purdue 19 University, Indianapolis. 20 MR. MYERS: Everybody knows that, 21 Paul, except for you. 22 MR. SMITH: See, I like bringing in 23 facts that everybody else knows. 24 Q. Did you work while you were in Page 11 1 high school? 2 A. Yes. 3 Q. Tell me about that. 4 A. Baby-sitting, clerking. 5 Q. Clerking for whom? 6 A. J.C. Penny. 7 Q. You grew up, I guess, in 8 Dayton? 9 A. Yes. 10 Q. Did you work in college? 11 A. Yes. 12 Q. Doing what? 13 A. I worked on campus in research 14 stores. 15 Q. Did you do any work while you 16 were working on your Master's? 17 A. I was employed by Eli Lilly 18 and Company. 19 Q. When did you begin work for 20 Eli Lilly and Company? 21 A. June, 1967. 22 Q. Have you ever taught in a 23 structured school? 24 A. Student teaching. Page 12 1 Q. While you were getting your 2 Bachelor's degree in teaching? 3 A. That's correct. 4 Q. But after you got your 5 Bachelor's degree in education from Bowling 6 Green, you went directly into the Master's 7 program, is that right? 8 A. Yes. 9 Q. What did you do, graduated 10 from Bowling Green, get hired by Lilly, the same 11 year, and started working on your Master's the 12 same year? 13 A. That's correct. 14 Q. Was that part of the 15 arrangement with Lilly when you were hired, that 16 they would hire you and you would continue your 17 education? 18 A. No. 19 Q. Was the Master's program 20 something that you did at night? 21 A. Yes. 22 Q. On a semi part-time basis? 23 A. Yes. 24 Q. How did you come to be hired Page 13 1 by Lilly? 2 A. Campus recruitment. 3 Q. What position did you apply 4 for? 5 A. A chemist in research. 6 Q. Your Bachelor's degree was in 7 education with a major in chemistry, and that was 8 sufficient for Lilly to hire you on as a chemist? 9 A. That's correct. 10 Q. So specifically what was your 11 first job title? 12 A. Associate chemist, as I 13 recall. 14 Q. How long did you hold that 15 position? 16 A. Probably until '71. 17 Q. What generally did your duties 18 include as an associate chemist? 19 A. I worked on making compounds 20 to be tested. 21 Q. In research? 22 A. Yes. 23 Q. Did you know what those 24 compounds were? Page 14 1 A. We made different kinds of 2 compounds to test, not knowing, you know, what 3 kind of activity they may or may not have. 4 Q. Were you researching any 5 particular area in connection with these 6 compounds? 7 A. We did a lot of broad 8 screening to see where there would be activity. 9 Q. Tell me about that, I don't 10 understand that. I'm not a chemist as you'll 11 soon find out. 12 A. What do you mean by tell me 13 about it? 14 Q. You said you did a lot of 15 broad scanning. 16 A. Broad screening. 17 Q. Screening. To see what 18 actions the compounds would produce? 19 A. What activities. 20 Q. How would you do that, and 21 what activities would you get? 22 A. This is going back a long 23 time. We would make compounds that the Ph.D in 24 the lab would think would be interesting, might Page 15 1 have some potential activity, and we would screen 2 them in several different screens that you could 3 test them against and see if there was any 4 activity. If they had any compounds that might 5 have activity, then you might want to develop 6 those compounds further to see how you can 7 enhance the activity or change it. 8 Q. Anything in particular of 9 activity that you were looking for, particular 10 type of activity? 11 A. I know I worked on some 12 anti-viral research. 13 Q. Anti-viral? 14 A. Uh-huh. 15 MR. MYERS: Yes, you need to say yes 16 so she can get it down. 17 A. Yes. 18 Q. Any psychotropic -- 19 A. No. 20 Q. -- medications? 21 A. No. 22 Q. Was this research that you 23 were doing in a particular division or area? 24 A. LRL research. Page 16 1 Q. But was LRL research that you 2 were working in divided into a particular 3 category? 4 A. I don't recall. 5 Q. Obviously somebody was 6 designing the research that you were doing to 7 achieve some general end, you weren't mixing salt 8 and pepper and setting it on fire to see if it 9 would burn. I would assume that Lilly doesn't 10 just mix compounds together and test them just 11 for the pure exercise of that nature. My 12 question to you is do you recall generally what 13 you were looking into? 14 A. Anti-virals. 15 Q. Anything else? 16 A. That I personally was looking 17 into? 18 Q. Yes. 19 A. When you do the broad 20 screening, you may get hits otherwise. We ended 21 up getting a herbicide out of it. 22 Q. But none of that work had to 23 do with medications or compounds that could be 24 used for treatment of psychiatric disorders? Page 17 1 A. No. 2 Q. What was your next job with 3 Lilly after you were associate chemist? 4 A. The next job title was an 5 organic chemist. 6 Q. How long did you hold that 7 position? 8 A. Well, I held it a short time, 9 and in the Fall of '71, my then husband took an 10 educational leave, so I exited Lilly to go with 11 him when he went to graduate school. I was not 12 going to go to graduate school. And then I was 13 rehired in May of '72. So I was gone about nine 14 months. Went back into research as an organic 15 chemist, and then held that until Fall of '78. 16 Q. By that time you had your 17 Master's degree when you returned to Lilly? 18 A. I had my Master's degree 19 before I left. 20 Q. So when you took an 21 educational leave, what course work did you 22 study? 23 A. I didn't take an educational 24 leave. Page 18 1 Q. All right. 2 A. My husband took an educational 3 leave, I quit the company to accompany him. 4 Q. He left Indianapolis. 5 A. Right. 6 Q. I see. Where did you all go? 7 A. Boston. 8 Q. Did you work while you were in 9 Boston? 10 A. Yes. 11 Q. What did you do there? 12 A. I was a chemist for Sheehan 13 Institute. 14 Q. What is the Sheehan Institute? 15 A. It was a small research 16 institute. Doctor Sheehan was a professor, and I 17 don't remember which university he was with, 18 either MIT or Harvard. They had a research 19 institute. 20 Q. What were they researching? 21 A. I know what I was researching. 22 Q. All right. 23 A. We were researching THC. 24 Q. THC? Page 19 1 A. Tetrahydrocannabinol. 2 Q. For what purpose? 3 A. I don't remember. 4 Q. What area were you involved? 5 A. I was only there for about 6 three months, I was a chemist making compounds. 7 Q. Tell me what your work, once 8 you returned to Lilly, was as an organic chemist 9 from 1972 until the Fall of 1978? 10 A. I did several different areas. 11 Q. Why don't you start with the 12 first then. 13 A. I was in the prep lab. 14 Q. For how long? 15 A. A relatively short period, 16 probably less than a year. 17 Q. What did you do there? 18 A. Attempt to start to scale up 19 compounds that had been made in the lab so they 20 could do some testing on them. 21 Q. What did that process involve, 22 scaling up? 23 A. Trying to make bigger batches. 24 Q. During that period of time, Page 20 1 were you working on any psychotropic compounds? 2 A. I don't remember what 3 compounds I worked on then. 4 Q. What was your next job in the 5 organic chemistry area? 6 A. I worked in the steroid area. 7 Q. Doing what? 8 A. Making compounds. 9 Q. Was Lilly researching steriods 10 at that time? 11 A. I guess so, that's the work I 12 was doing. 13 Q. At that time were they 14 manufacturing any steriods? 15 A. I don't know. 16 Q. Are they now? 17 A. I don't know. 18 Q. Have they ever? 19 A. I don't know. 20 Q. How long were you working on 21 steriods? 22 A. Maybe two to three years. 23 Q. Did you enjoy that work? 24 A. It was all right, research was Page 21 1 pretty difficult. 2 Q. What was your next job in the 3 organic chemistry? 4 A. Cephalosporin research. 5 Q. Working on Ceclor? 6 A. I didn't work on Ceclor. 7 Q. Lilly manufacturers Ceclor, 8 don't they? 9 A. Yes. 10 Q. Ceclor is a Cephalosporin, 11 isn't it? 12 A. Yes. 13 Q. What was your job in the 14 Cephalosporin research area? 15 A. We were looking for new 16 products. 17 Q. And specifically what are you 18 doing? 19 A. Making compounds that were 20 like structure activity relationships. You would 21 modify your compounds, see what kinds of 22 activity, if any, you would get. 23 Q. How long did you do that? 24 A. Until the Fall of '78. Page 22 1 Q. Was most of this work as an 2 organic chemist from 1972 to the Fall of 1978 3 done in a lab -- 4 A. Yes. 5 Q. -- at a bench type setting, 6 where you were working with chemicals and organic 7 compounds and making preparations, things of that 8 nature? 9 A. Yes. 10 Q. And I guess you would do 11 analysis also, chemical analysis of these various 12 compounds? 13 A. No, it would be sent to be 14 analyzed. 15 Q. Who was head of that area at 16 that time? 17 A. Doctor Vanhilegan. 18 Q. Did you have the same 19 supervisor throughout your six year tenure? 20 A. No. 21 Q. Who was your last supervisor? 22 A. Robin Cooper. 23 Q. That specific group where you 24 were working in organic chemistry from 1972 to Page 23 1 1978, did that group have a particular name or 2 designation? 3 A. I mean we went by department 4 number, MC seven oh five. I don't remember what 5 the title was. 6 Q. In other words, if you looked 7 at a corporate organizational structure chart of 8 Lilly research labs, how would you all -- how 9 would that group within which you worked be 10 designated? 11 A. Probably with the department 12 number of MC seven oh five. I really don't 13 remember what the title was. 14 Q. Up until 1978, did you do any 15 work on Fluoxetine? 16 A. No. 17 Q. Up until 1978, did you do any 18 work that involved clinical trial work? 19 A. I don't understand your 20 question. 21 Q. You don't know what a clinical 22 trial is? 23 A. I know what a clinical trial 24 is. I was in organic chemistry, so that's why I Page 24 1 don't understand your question. 2 Q. Did that work as an organic 3 chemist have anything to do with clinical trials, 4 for instance would you have a situation where you 5 were doing research on a compound, that compound 6 was also being investigated in a clinical trial, 7 and there might be data sent in or material sent 8 in for you to analyze or for you to investigate 9 as an organic chemist? 10 A. No. 11 Q. Are we on the same wavelength 12 now? 13 A. Yes. 14 Q. Ms. Ashbrook, I did not give 15 you any preparatory remarks that we normally 16 give. You understand that your deposition is 17 being taken here in connection with claims made 18 by various plaintiffs against Lilly as a result 19 of their ingestion of Fluoxetine Hydrochloride, 20 brand name Prozac, manufactured by Lilly. Do you 21 understand that? 22 A. Yes. 23 Q. My name is Paul Smith, we've 24 been introduced. I represent several plaintiffs Page 25 1 in several cases involving this medication. Do 2 you understand that? 3 A. Yes. 4 Q. Your deposition can and will 5 be used in the trial of many of these cases. Do 6 you understand that? 7 A. Yes. 8 Q. For that reason, and it's 9 important that we be communicating and that we 10 don't have a situation that arises later where 11 there is some doubt with respect to whether or 12 not you and I are communicating in our questions 13 and in our answers. Sometimes my questions 14 aren't clear, I talk with a Texas accent, and 15 sometimes I may not understand your response. So 16 if you don't understand my question or have any 17 problem with one of my questions, would you feel 18 free to let me know, and we'll be glad to clarify 19 it. 20 A. Yes. 21 Q. All right? 22 A. Yes. 23 Q. And I'll do the same with you. 24 If I don't understand your answer, I may ask for Page 26 1 an explanation so that we'll both know that we're 2 communicating in getting facts, all right? 3 A. Yes. 4 Q. Why did you leave the organic 5 chemistry department in the Fall of 1978? 6 A. I went on maternity leave. 7 Q. And how long were you on 8 maternity leave? 9 A. Four months. 10 Q. When did you return to Lilly, 11 Ma'am? 12 A. In January. 13 Q. Did you start another job? 14 A. I initially was still in 15 organic research, but I did interview for another 16 job. 17 Q. What other job was that? 18 A. It was for a position of a 19 clinical research administrator. 20 Q. Did you become a clinical 21 research administrator? 22 A. Yes, I did. 23 Q. When? 24 A. Early '79. So I came back in Page 27 1 January, February, March, kind of time frame. 2 Q. So you began -- were you hired 3 as a clinical research administrator? 4 A. Yes. 5 Q. Then you began that work in 6 February or March of 1979? 7 A. Yes. 8 Q. You need to give audible 9 answers. 10 A. I know. 11 Q. That would have been in a 12 different division than the division you were in? 13 A. That's correct. 14 Q. And how was that division 15 designated? 16 A. Medical. 17 Q. Did it have a number like you 18 had when you were an organic chemist? I think 19 you said it was MD seven oh five -- 20 A. MC. 21 Q. MC seven oh five? 22 A. Yes. It did have a number, 23 the numbers have changed, I don't recall what it 24 was when I joined it. Page 28 1 Q. Do you remember what it is -- 2 that number would be now? 3 A. Well, there's several 4 different numbers. As CRAs, I think it's either 5 MC six six one or MC six six two, it's one of 6 those two. 7 Q. Was this the first time you 8 had worked in the medical division at Lilly 9 research labs? 10 A. Yes. 11 Q. The medical division was at 12 that time still a part of Lilly research labs? 13 A. Yes. 14 Q. Why did you interview to be a 15 clinical research administrator? 16 A. I wanted a career change. 17 Q. Why? 18 A. I had worked in the lab for 19 ten years and felt that it was time to broaden my 20 horizons and continue to grow. 21 Q. Did you have to make a 22 separate application to be a CRA at that time? 23 A. I had a reentry application 24 when I came back from maternity leave, if that's Page 29 1 what you mean, but it wasn't -- 2 Q. A new job application. 3 A. No. 4 Q. Had you been considering for 5 some time moving out of the organic chemistry 6 research area? 7 A. I had thought about it 8 probably for a couple of years ahead of that. 9 Q. Getting a little burned out? 10 A. Yes. 11 Q. Wanting a change, is that 12 right? 13 A. Yes. 14 Q. What about the CRA position 15 attracted your interest? 16 A. It was an opportunity for me 17 to continue to be able to grow and develop and 18 learn something different. It had 19 responsibility, more so than I had in the 20 research labs. 21 Q. Who headed up the CRAs at that 22 time? 23 A. Gene Crum. 24 Q. Do you remember who you Page 30 1 interviewed with for that initial CRA job? 2 A. Gene Crum. 3 Q. Anybody else? 4 A. No. 5 Q. Were there any type of 6 educational or work experience that was required 7 in order to apply for the CRA position at the 8 time you applied? 9 A. Help me understand that. 10 Q. Were there any minimum job, 11 educational or experience requirements that had 12 to be met before an individual could apply as a 13 CRA? 14 A. Preferred to have a scientific 15 background. 16 Q. Which you did. 17 A. Yes. 18 Q. Had the company or Lilly 19 research labs circulated information concerning 20 this job and its availability? 21 A. No. 22 Q. How did you come to apply for 23 the job then? 24 A. When I came back from Page 31 1 maternity leave and talked with my personnel 2 representative, they indicated that there were 3 jobs open as CRAs, would I potentially be 4 interested. 5 Q. All right. So you went back 6 to human resources when you came back from 7 maternity leave and said I'm a little burned out, 8 what else do you have that I could qualify for 9 that might be interesting that's open, and they 10 advised you of the CRA position? 11 A. Yes. 12 Q. Do you recall if there was any 13 other positions that were open that you had an 14 interest in at that time? 15 A. No. 16 Q. Did Mister Crum explain to you 17 at the time of your interview what the job of CRA 18 at Lilly entailed? 19 A. Yes. 20 Q. And what did he explain to you 21 that job was? 22 A. As regulatory CRA, we would be 23 reviewing the information that came in from 24 patients on our clinical trials, on case report Page 32 1 forms. The data would be computerized. We 2 needed to make sure that as the data came in and 3 what was put in the computer agreed. And that 4 for studies of a longer duration, chronic 5 studies, that what appeared in one visit, if the 6 information needed to continue on to the next 7 visit, that it was there. So there was a lot of 8 checking, a lot of looking at the data for 9 errors, if something wasn't captured right or it 10 had been written down wrong on a case report form 11 before it came to Lilly, and would entail working 12 on developing the final reports from the clinical 13 trials that were completed. 14 Q. What about that job 15 description was attractive to you? 16 A. Again, additional 17 responsibility, opportunity to become still part 18 of research, but part of where you're working 19 with -- you're working with compounds that could 20 potentially become products as opposed to in a 21 lab you can do research for years on end and 22 nothing makes it to that point in time. So it's 23 an opportunity to see what does happen to those 24 that have the potential to become products. Page 33 1 Q. All right. And I assume you 2 began your work as a CRA in February or March of 3 1979? 4 A. That's when I came into the 5 medical department, yes. 6 Q. And that CRA stands for 7 clinical research -- 8 A. Administrator. 9 Q. -- administrator. Who was 10 your first supervisor? 11 A. Gene Crum. 12 Q. Did you have anybody working 13 under you initially? 14 A. No. 15 Q. What was your first project 16 that you worked on? 17 A. Worked on internal medicine 18 compounds. 19 Q. Exclusively? 20 A. Yes. 21 Q. Were those internal medicine 22 compounds being studied in clinical trials? 23 A. Yes. 24 Q. On humans? Page 34 1 A. Yes. 2 Q. And did those compounds become 3 Lilly products? 4 A. Yes. 5 Q. What products were you working 6 on? 7 MR. MYERS: You can tell him the ones 8 that were ultimately marketed, but she's not 9 going to tell you what wasn't marketed. 10 MR. SMITH: That's why I asked what 11 became Lilly products because I'm not interested 12 in what never came through. 13 A. Denoxeprofen. 14 Q. You're going to have to spell 15 that for her. 16 A. D-E-N-O-X-E-P-R-O-F-E-N. 17 Q. What type of medication is 18 that? 19 A. Anti-inflammatory for 20 arthritis. 21 Q. And how long did you work on 22 the Denoxeprofen? 23 A. Probably about a year and a 24 half. Page 35 1 Q. So we would be from 1979 -- 2 A. Oh, probably not that long, 3 probably about a year. 4 Q. Up to 1980 sometime? 5 A. It could have been. 6 Q. During that initial one-year 7 period of time, your work was devoted to 8 Denoxeprofen? 9 A. Yes. 10 Q. Were there several clinical 11 trials ongoing at that time? 12 A. Yes. 13 Q. Had the medication been 14 approved for marketing at the time you were 15 working on it? 16 A. No. 17 Q. This was in the preapproval 18 clinical trials? 19 A. Yes. 20 Q. When was it granted FDA 21 approval for marketing, do you recall? 22 A. I don't remember. 23 Q. At that time that you were 24 working on that anti-inflammatory medication, did Page 36 1 you review case report forms? 2 A. Yes. 3 Q. Did you computerize data? 4 A. Yes. 5 Q. I would assume you didn't 6 actually do data entry. 7 A. No. Reviewed the data that 8 had been entered. 9 Q. And did you check for errors 10 in the data that had either been received or 11 entered? 12 A. Yes. 13 Q. Did you develop any final 14 reports or were you involved in any submissions? 15 A. Yes. 16 Q. To the Food and Drug 17 Administration? 18 A. Yes. 19 Q. Did your work at that time 20 involve assistance in preparing scientific 21 articles concerning that drug? 22 A. Do you mean by scientific 23 articles, journal articles? 24 Q. Yes. Page 37 1 A. No. 2 Q. Do you recall who the medical 3 monitor was of that drug? 4 A. Doctor MacLogeck. 5 MR. MYERS: Mister Smith can spell it 6 instantly. 7 MR. SMITH: If you think I'm going to 8 make everybody's work that much easier, I didn't 9 even write it down. 10 Q. Did you get any promotions or 11 did you move up as a clinical research 12 administrator during the period of time that you 13 were working on Denoxeprofen? 14 A. Not that I recall. 15 Q. You remained basically on the 16 same level. 17 A. Yes. 18 Q. Mister Crum was your 19 supervisor? 20 A. Yes. 21 Q. And you had nobody working 22 under you for whom you were directly responsible 23 for supervision. 24 A. That's correct. Page 38 1 Q. What was your next job? 2 A. Worked in the oncolytic area, 3 worked on compounds in the oncolytic area. 4 Q. Still you're a clinical 5 research administrator? 6 A. That's correct. 7 Q. But your work moved from this 8 anti-inflammatory medication to cancer drugs? 9 A. Right. 10 Q. And how long did you work on 11 that in that area? 12 A. That was probably under six 13 months. 14 Q. Why were you changed from the 15 anti-inflammatory drug to the oncological drug 16 compounds? 17 A. Where we were with the 18 clinical trials on Denoxeprofen, they needed help 19 in the oncolytics and there was enough other 20 people to meet the needs for Denoxeprofen at that 21 time. 22 Q. The oncology area in which you 23 were working, were you investigating any 24 compounds that were being used in clinical Page 39 1 trials? 2 A. Yes. 3 Q. Did any of those compounds 4 become drugs that were approved and have since 5 been marketed by Lilly as a medication? 6 A. I don't remember the names or 7 the name of the drug that I was on for that short 8 period of time. And there was some that were 9 approved in Europe that were never approved here, 10 and I don't remember which one it was. 11 Q. Was Mister Crum still your 12 supervisor? 13 A. Yes. 14 Q. And during that period of time 15 that you were working on cancer studies, did you 16 have anybody for whom you had responsibility for 17 direct supervision? 18 A. No. 19 Q. Was it basically the same type 20 of work on clinical studies with respect to the 21 cancer compounds as you had been doing for 22 Denoxeprofen? 23 A. Yes. 24 Q. In your work on Denoxeprofen, Page 40 1 did you review reports of adverse experiences 2 that had occurred during the clinical trials? 3 A. Yes, that was part of the 4 clinical trial case report forms. 5 Q. And in your work on the cancer 6 drugs, did you receive and review adverse 7 experiences in connection with those compounds? 8 A. What was on the case report 9 forms. 10 Q. Why were you changed out of 11 the oncology area or out of the oncology studies 12 to another medication? 13 A. My father had recently died 14 with cancer, and I couldn't deal with case report 15 forms. 16 Q. And, so, you requested to be 17 assigned to work on some studies involving 18 different types of medications? 19 A. I just asked if it was 20 possible to work on something else. 21 Q. And I guess Mister Crum was 22 able to accomodate you -- your desires in that 23 area? 24 A. Yes. Page 41 1 Q. What were you switched to? 2 A. Fluoxetine. 3 Q. When did you begin your work 4 on the Fluoxetine studies? 5 A. Again, I think it was in like 6 the 1980 time frame. It's been a while ago, and 7 it's kind of blurry. 8 Q. As I understand it, you 9 started your work in the oncology section in 10 1980, you did that work for approximately six 11 months, and then you were switched to Fluoxetine. 12 So would it be safe to say '81? 13 A. Definitely. 14 Q. And at the time you began your 15 work as a clinical research administrator in 16 connection with the Fluoxetine studies, was 17 Mister Crum still your supervisor? 18 A. Yes. 19 Q. And at the time you began your 20 work as a clinical research administrator on the 21 Fluoxetine studies, did you have anybody over 22 whom you had responsibility for direct 23 supervision? 24 A. Initially? Page 42 1 Q. Yes. 2 A. There was a secretary that was 3 being shared. 4 Q. Was this the first time you 5 had had a secretary as a CRA? 6 A. We utilized secretaries, but a 7 lot of times we utilized the manager's secretary 8 to get stuff done, so yes. 9 Q. Who was the medical monitor 10 responsible for Fluoxetine studies at the time 11 you began your work as a CRA on Fluoxetine? 12 A. Paul Stark. 13 Q. Where was Fluoxetine in the 14 clinical study area when you began as a clinical 15 research administrator? 16 MR. MYERS: When you say where, do you 17 mean physically or how far along was it? 18 Q. Phase one, phase two, phase 19 three. 20 A. Early phase two. 21 Q. Phase two is human studies? 22 A. Yes. 23 Q. And still some safety efficacy 24 animal studies, is that right? Page 43 1 A. Phase two is the studies in 2 your patient population you're studying, so not 3 the normal healthy volunteers, but in depressed 4 patients. 5 Q. How many clinical research 6 administrators were on board studying -- involved 7 in the Fluoxetine studies at the time you began? 8 A. There was one other one. 9 Q. Who was that? 10 A. Giselle Soyez. 11 Q. Soyez? 12 A. S-O-Y-E-Z. 13 Q. All right. There was you, 14 Giselle Soyez, Paul Stark was the medical 15 monitor, right? 16 A. Correct. 17 Q. Was there any research 18 physicians at that time working on Fluoxetine? 19 A. Not that I was aware of. 20 Q. As a clinical research 21 administrator, initially, would you work with 22 clinical research physicians? 23 A. Not closely. 24 Q. There would be occasions, Page 44 1 though, when you would need guidance from a 2 medical doctor, a physician, in connection with 3 some of your duties as a clinical research 4 administrator; is that not correct? 5 A. Very minor. 6 Q. Initially in connection with 7 your Fluoxetine work, who would you go to for 8 assistance in the medical area? 9 A. Paul Stark was the monitor on 10 the study. 11 Q. So he would be the first 12 individual you would go to? 13 A. Yes. 14 Q. You have to give an audible 15 answer. 16 A. Yes. 17 Q. But you don't remember any 18 other clinical research physicians at that time 19 who were involved with Fluoxetine? 20 A. No. 21 Q. You know Doctor Beasley, 22 Doctor Heilegenstein, Doctor Wernicke, Doctor 23 Kotsanos, all of those physicians had been 24 involved with Fluoxetine at various times. Page 45 1 A. Yes. 2 Q. My question to you is: Do you 3 have any recollection of them being involved -- 4 A. No. 5 Q. -- at that time? 6 A. No. 7 Q. Who else was involved in the 8 Fluoxetine early phase two studies at the time 9 you began as a CRA? 10 A. The three of us that I had 11 indicated. 12 Q. So you were kind of a pioneer 13 with Fluoxetine, weren't you? 14 A. (Witness moves head up and 15 down.). 16 Q. Is that a yes? 17 A. Yes, that's a yes. Can I go 18 back and ask you a question, I mean what do you 19 mean by who else was involved, in medical? 20 Q. Yes. 21 A. Okay. Then my answer stands. 22 Q. I understand that there were 23 several clinical trials going on with 24 investigators, that there were data entry Page 46 1 personnel, that there were -- 2 A. Yes, there were data entry 3 personnel. When I first started, we weren't to 4 that point yet, so literally there were the three 5 of us. 6 Q. Stark, Ms. Soyez, and 7 yourself; correct? 8 A. That's correct. 9 MR. MYERS: Can we take a short break? 10 MR. SMITH: Yes. 11 (A SHORT RECESS WAS TAKEN.) 12 Q. Ms. Ashbrook, when you began 13 your work as a clinical research administrator 14 with respect to Fluoxetine, did you do any 15 reading or research in connection with Fluoxetine 16 itself or what had been done up to that point? 17 A. There was a clinical 18 investigators brochure. 19 Q. All right. 20 A. I reviewed that. 21 Q. Anything else? 22 A. There were some published 23 articles on some of the efficacy parameters we 24 were going to capture. Page 47 1 Q. Do you remember what those 2 were? 3 A. The actual title of the 4 papers? 5 Q. Yes, or who wrote them. 6 A. No. 7 Q. They were articles that had 8 been written by Lilly people? 9 A. No. 10 Q. Or investigators? 11 A. No, they were articles on, 12 like, what is the Hamilton Depression Scale, how 13 do we use that. I don't know who wrote them, 14 probably -- 15 Q. Mister Hamilton? 16 A. I don't -- well, he could 17 have. I mean other people had published on that. 18 There was also a publication from the FDA on how 19 to study antidepressants. 20 Q. Do you remember the name of 21 that publication? 22 A. No. 23 Q. But you're sure it was an FDA 24 publication? Page 48 1 A. I think so. 2 Q. Would you still have that? 3 A. No. 4 Q. Do you remember what happened 5 to it? 6 A. Probably got transferred on 7 when I left my work on Fluoxetine, stayed with 8 the files. 9 Q. You didn't maintain that in 10 your files? 11 A. No. 12 Q. Would this have been something 13 that might have come from one of the Lilly 14 libraries? 15 A. Probably came from regulatory. 16 Q. Who at regulatory would have 17 given that to you? 18 A. I don't remember. 19 Q. Anything else that you did to 20 familiarize yourself with Fluoxetine or the 21 studies that had been done up to that point? 22 A. Reviewed the protocols that we 23 were collecting the data on. 24 Q. Anything else? Page 49 1 A. Not that I remember. 2 Q. Did you read anything in 3 connection with the chemical nature of Fluoxetine 4 or serotonin or the chemical nature of 5 depression? 6 A. I read what was in the 7 clinical investigational brochure. 8 Q. Nothing other than what was 9 contained in the clinical investigation brochure. 10 A. That's correct. 11 Q. Did you talk to anyone 12 concerning Fluoxetine or the status of the 13 studies, outside of Doctor Stark? 14 A. Not that I recall. 15 Q. Did you talk with Doctor 16 Zerbe, Doctor Fuller, Doctor Long? 17 A. I had talked to Doctor Fuller, 18 but I don't know in a time frame if it was at the 19 beginning or when, but yes, I had -- did talk to 20 Doctor Fuller. 21 Q. Do you remember the content of 22 your initial discussions with Doctor Fuller? 23 A. He talked to me about, in 24 Fluoxetine, and what it was as being a serotonin Page 50 1 reuptake inhibitor. 2 Q. Do you think that would have 3 been within the first few months of your work? 4 A. I don't recall. 5 Q. Do you remember why you were 6 going to him to get this information or have this 7 discussion? I don't know that you were going to 8 him to get information. 9 A. He was the one who had done a 10 lot of the early research on serotonin reuptake 11 inhibitors. 12 Q. And was there a particular 13 problem that you needed his guidance on? 14 A. No, just to probably better 15 understand what I had read in the clinical 16 investigational brochure. 17 Q. Was this part of a seminar or 18 was this a one-on-one meeting where -- 19 A. Probably went over and talked 20 to him in his office. 21 Q. In early 1981, when you came 22 on as a clinical research administrator with 23 respect to Fluoxetine, how many clinical studies 24 were ongoing at that time? Page 51 1 A. At that time there were three 2 that were currently ongoing that I was aware of. 3 Q. Human studies? 4 A. Yes. 5 Q. They were all three human 6 studies? 7 A. Yes. 8 Q. Was Doctor Stark overseeing 9 each of these studies? 10 A. Yes. 11 Q. And were there any human 12 studies that had been completed at that time? 13 A. I think that there were. 14 Q. Can you give me any details on 15 the number or nature of those studies that had 16 been completed? 17 A. There were early protocols 18 with single investigators, but I wasn't privy to 19 those, I did not see them. 20 Q. Were there any studies when 21 you came on that were in the planning stage or 22 that were being formulated? 23 A. I don't know. 24 Q. The three ongoing studies that Page 52 1 were in progress at the time that you came on, 2 were these multi-center studies or were these 3 single investigator, single location studies? 4 A. They were single investigator, 5 but different investigators had the same protocol 6 or was studying it the same. When the 7 information was computerized, we combined that 8 information. 9 Q. So there were three different 10 investigators working at three different 11 locations? 12 A. There were more than three 13 investigators. 14 Q. All right. How many 15 investigators were there? 16 A. I can't say with certainty. 17 Q. Would it have been more than 18 five? 19 A. Could have been right around 20 there. 21 Q. How many protocols were being 22 used? 23 A. My best recollection is 24 through the project codes, not the protocol Page 53 1 numbers. When I refer to the three studies, I 2 referred to three project codes. 3 Q. All right. Each project has 4 to have a protocol, is that right? 5 A. We pooled some of that early 6 information as I had previously stated. 7 Q. Okay. You're losing me. 8 A. For example, one project was 9 HCAC. If there were two investigators, it was 10 two different protocols, but they were comparing 11 Fluoxetine to the same comparitor. So, 12 therefore, when you create a data entry system, 13 it all looks the same, but you can identify which 14 investigator and then go back to the protocol so 15 you would know whose data was what. But it was 16 all studying Fluoxetine versus a comparitor. 17 Q. That was going to be my next 18 question. Of those three ongoing studies, were 19 these placebo controlled, double-blind comparitor 20 studies, how would you characterize them in that 21 connection? 22 A. It was both, the three ongoing 23 with the three studies. 24 Q. You weren't using in each -- Page 54 1 or you had some that were comparitor studies, 2 some were placebo? 3 A. That's correct. 4 Q. Do you remember the comparitor 5 drug in either one of them? 6 A. Amitriptyline was one of the 7 comparitor drugs, placebo was a comparitor, and I 8 think Imipramine. 9 Q. All were being developed in 10 connection with depressed patients? 11 A. Yes. 12 Q. Was there any other further 13 subset of depressed patients who were being 14 examined? 15 A. What do you mean by -- 16 Q. Like elderly, like young, you 17 follow what I'm saying? There were some studies 18 that studied the effects of Fluoxetine in 19 connection with a geriatric population. 20 A. No. 21 Q. These were all straight? 22 A. Major depressive disorder. 23 Q. DSM three, major depressive 24 disorders? Page 55 1 A. Yes. 2 Q. Individuals. 3 A. Yes. 4 Q. Were these all outpatient 5 studies? 6 A. As I recall, yes. 7 Q. What was the patient 8 population of these studies? 9 A. What do you mean by that? 10 Q. How many patients were 11 involved in the studies? 12 A. The numbers of patients? 13 Q. Yes. 14 A. I don't remember. 15 Q. There were some studies that 16 involved only twenty patients, initially. We 17 talked to Doctor Stark, he told us about one 18 study early on that just involved twenty 19 patients. And then there had been some studies 20 that involved thousands of patients. 21 A. Yes. 22 Q. I'm trying to get an idea of 23 where we are. 24 A. They were of the smaller Page 56 1 nature. Specifically how many, at this point, I 2 don't remember. 3 Q. Do you remember if any of 4 those studies were pivotal studies or ended up 5 being pivotal studies? 6 MR. MYERS: Before she answers, let me 7 object to the form since the term pivotal, at 8 least as it's being used in this litigation, is a 9 regulatory term. But if you know, tell him, if 10 you know whether or not they were, quote, 11 unquote, pivotal. 12 A. I was going to ask what you 13 were defining as pivotal. 14 Q. That term as being used by the 15 Food and Drug Administration in connection with 16 their requirements that some studies be pivotal 17 studies. 18 A. In the depressed patient 19 population, the FDA requires placebo controlled 20 studies, those are the pivotal ones. 21 Q. So would any of these three 22 studies have met the FDA definition of pivotal 23 studies? 24 A. Yes. Page 57 1 Q. Do you remember what the study 2 number was? 3 A. The project code? 4 Q. Project code or study number 5 of the pivotal studies. 6 A. HCAC. 7 Q. And what was the study number? 8 A. That's where -- I don't 9 remember. 10 Q. All right. Who were the 11 investigators in that HCA pivotal study? 12 MR. MYERS: Paul, right now I'm going 13 to instruct her not to answer that for this 14 reason: If those investigators are not the 15 investigators disclosed by the FDA in the summary 16 basis for approval as being pivotal, the 17 disclosure of that information would constitute 18 disclosure of a highly valuable and proprietary 19 trade secret, it might well involve violation of 20 one or more FDA regulations, and it is also 21 covered by one or more orders of both the MDL 22 court and the Fentress court, and I simply do not 23 know if those investigators were the ones 24 disclosed by the FDA. I will be happy either Page 58 1 presently or at the break to try to ascertain 2 that. 3 MR. SMITH: Would you ask Ms. Ashbrook 4 at the break who those investigators were and see 5 if you can determine -- 6 MR. MYERS: On those three studies -- 7 I'll be glad to do that. But presently, why 8 don't we move along. But I will ask that. 9 MR. SMITH: Okay. 10 Q. Where were those studies 11 located, do you remember what cities they were 12 in? 13 A. No. 14 Q. Were they in various locations 15 throughout the country? 16 A. Yes. 17 Q. And you say there may have 18 been three to five investigators in connection 19 with those three studies, ongoing at the time you 20 began your work as a clinical research 21 administrator in the Fluoxetine area? 22 A. That's correct. 23 Q. Now, when you came on in the 24 Fluoxetine area, was there a pool of information Page 59 1 concerning individuals who had been studied in 2 the clinical trials? 3 A. I don't understand what you're 4 asking. 5 Q. In other words, there were 6 some studies, as I understand it, that had been 7 completed by the time you came on? 8 A. Yes. 9 Q. And the data from those 10 studies would have been sent back to Indianapolis 11 in the form of case report forms. 12 A. Yes. 13 Q. There were also studies that 14 were ongoing that data was being received 15 periodically from the -- 16 A. Yes. 17 Q. -- sites of the studies, and 18 held there at Indianapolis; correct? 19 A. Yes. 20 Q. My question to you is: How 21 were you keeping that data that you had at the 22 time you came on? 23 A. One of my first tasks when I 24 came on board with the product was to work with Page 60 1 the systems folks to design an input system so we 2 could computerize it. 3 Q. Is my understanding correct 4 that at the time you came on in 1981 that there 5 wasn't any computer data base in connection with 6 clinical trial information up to that point on 7 Fluoxetine? 8 A. That's correct. 9 Q. So all the clinical study data 10 was in paper form? 11 A. Yes. 12 Q. How much paper are we talking 13 about? 14 A. It was very early on, those 15 studies, I don't know that any had been received 16 in-house for those three studies. The previous 17 ones, I didn't see those. 18 Q. You never laid eyes on that 19 amount of paper? 20 A. Not at that point, no. 21 Q. But you had studies that were 22 ongoing, three studies, when you came on? 23 A. They had just started. 24 Q. And when you say just started, Page 61 1 within what period of time? 2 A. They had actually gone out, 3 started the studies -- 4 Q. Patients had been enrolled. 5 A. Yes, but the drug had been 6 delivered to the sites, so there was probably 7 opportunity for patients to have been enrolled. 8 I don't recall the data had come back into Lilly 9 at that point in time. 10 Q. At that time, how often was it 11 required that the -- or what were the 12 requirements in connection with how often the 13 investigators were to return data to Lilly? 14 A. I don't recall. 15 Q. In your review of the clinical 16 investigators brochure, in your discussions with 17 Doctor Fuller, in your preliminary start-up mode 18 where you were trying to assimilate as much 19 information about Fluoxetine as you could, was 20 there any issue that you saw in connection with 21 whether or not ingestion of Fluoxetine caused or 22 could be related to suicidal ideation, suicidal 23 acts or suicide attempts? 24 A. Start the beginning of your Page 62 1 question again. I'm sorry, I hear what you're 2 asking, but what was the initial part of the 3 question? 4 MR. SMITH: I don't have any idea. 5 MR. MYERS: Let the court reporter 6 read it back. 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED TESTIMONY.) 9 A. No. 10 Q. When did that first -- when 11 did that issue first come up as far as you 12 recall? 13 A. I don't recall it coming up 14 when I was working with Fluoxetine. 15 Q. And how long did you work with 16 Fluoxetine? 17 A. Through the Fall of '88. 18 Q. All right. Your initial work, 19 I believe you stated, was to design an input 20 system? 21 A. Work with the systems analyst 22 to design. 23 Q. Had you had any computer 24 expertise up to that point? Page 63 1 A. No, that's why I was working 2 with a systems analyst, they're the experts. 3 Q. Tell me what you did in 4 connection with getting the data that you had and 5 that you knew you would be receiving into 6 computerized form? 7 A. We worked with the case report 8 forms, we wanted to make sure that all the data 9 elements that were on the case report form were 10 being collected to be put into the computer. The 11 systems analyst would design the best way to 12 capture that information, worked with them to 13 make sure we didn't leave anything out, that we 14 were capturing all the data fields that we needed 15 to capture. 16 Q. Who was the systems analyst 17 you initially worked with? 18 A. As I recall, it was Ed 19 Korteter, K-O-R-T-E-T-E-R. 20 Q. Is he still with Lilly? 21 A. I don't know. 22 Q. Anybody else in the systems 23 area that you were working with? 24 A. Not at that point. Page 64 1 Q. Who was the next individual in 2 systems that you worked with? 3 MR. MYERS: On that project or any 4 other project? 5 MR. SMITH: Well, I'm assuming -- 6 Q. Until 1988, from the time you 7 started working with systems analysts, you had to 8 continue to work with them? 9 A. Right. 10 Q. I know that the system was 11 changed on several occasions. 12 A. Right. 13 Q. My question is who was the 14 next systems analyst that you used? 15 A. The next one I recall was 16 Maureen Murray. 17 Q. Maureen Murray? 18 A. Yes. That wasn't her name 19 then, though. 20 Q. Is she still here with Lilly? 21 A. Yes. 22 Q. What else did you do with that 23 initial systems analyst? You say you worked with 24 case report forms to capture the information off Page 65 1 the case report forms, to get them into a 2 computer usable mode. What else did you do? 3 A. With the systems analyst? 4 Q. Yes. 5 A. That was basically it. I'm 6 having trouble reconstructing at that point to 7 other points down the line. 8 Q. All right. 9 A. But it was data entry system 10 for data capture. 11 Q. At the time you came on with 12 Fluoxetine, were there any outside U.S. studies 13 being done? 14 A. No. 15 Q. Were there any outside U.S. 16 studies being planned? 17 A. At the time I came on? 18 Q. Yes. 19 A. I don't know that. I know one 20 of the studies was conducted in Canada. 21 Q. One of the studies that had 22 been completed? 23 A. No. 24 Q. One of the ongoing studies was Page 66 1 a Canadian study? 2 A. One of the investigators in 3 HCAE was in Canada. 4 Q. Do you know whether or not 5 that was a pivotal study? 6 A. It was not a placebo 7 controlled study. 8 Q. All right. Was that study -- 9 I'm not clear. Was that study one of the three 10 ongoing studies that was underway when you came 11 on, or it was completed? 12 A. No, it was not completed. It 13 was one of those early groupings of studies. Now 14 they didn't -- hadn't all started. They were -- 15 I don't remember when the investigator started on 16 that study. 17 Q. Okay. 18 A. That particular investigator 19 started. 20 Q. Was HCAC a comparitor study? 21 A. Yes. 22 Q. Do you remember the comparitor 23 drug? 24 A. Amitriptyline. Page 67 1 Q. And HCAC was placebo 2 controlled? 3 A. Yes. 4 Q. You could have placebo versus 5 Fluoxetine, you can have Fluoxetine versus 6 comparitor, and you can have Fluoxetine versus 7 placebo and comparitor; isn't that correct? 8 A. That's correct. 9 Q. And if a study is Fluoxetine 10 versus placebo versus comparitor, can that be a 11 pivotal study? 12 A. Yes, placebo is part of the 13 study. 14 Q. As long as there's a placebo 15 arm in the study, it can be a pivotal study. 16 A. Yes. 17 Q. Regardless of whether or not 18 there's a comparitor drug that's another arm. 19 A. Yes. 20 Q. How long did it take you 21 initially to get the initial computer system set 22 up? 23 A. I don't remember. 24 Q. Approximately, within a year? Page 68 1 A. Yes. 2 Q. Within six months? 3 A. I would say probably somewhere 4 six months to a year. 5 Q. What system was it put on, how 6 did you designate the system? 7 A. What do you mean by system? 8 Q. The computer system. 9 MR. MYERS: I think he wants to know 10 what you called it. 11 A. Entrex. 12 Q. Entrex, E-N-T-R-E-X? 13 A. Yes. 14 Q. Entrex what? 15 A. Entrex, that's all I knew it 16 as. 17 Q. Was that a separate computer 18 to receive and assimilate data for the Fluoxetine 19 clinical trials or was that part of a big mega 20 computer down in the basement of Lilly somewhere 21 with just a different software that was put onto 22 that? 23 MR. MYERS: I don't -- you want to 24 know if it was used just for Fluoxetine as Page 69 1 opposed to used across the board? 2 Q. I assume there was a memory in 3 that there was software designed just for 4 Fluoxetine, or did you use the big Lilly hard 5 drives or did you use separate computers? You're 6 looking at me like I'm crazy. 7 MR. MYERS: I think I'll object to the 8 form of the question because it assumes certain 9 things that I don't know to have been established 10 or not. 11 MR. SMITH: I thought you would 12 stipulate I was crazy. 13 MR. MYERS: No, I'll wait until after 14 the lunch break. 15 Q. Tell me how the system worked 16 then. 17 A. I didn't know, I mean this 18 precedes PCs and all of that, this is before that 19 was a mechanism. So Entrex was a system, but I 20 don't know -- I don't know what it was. 21 Q. Did you ever see it, the 22 Entrex machines? 23 A. It was a terminal for entering 24 the data in. Page 70 1 Q. Where was the memory stored, 2 there at the same location as the terminal was 3 located? 4 A. There's a computer room at 5 Lilly, I assume it was in there, but I, for a 6 fact, I don't know. 7 Q. You see I'm totally computer 8 illiterate. 9 A. Okay. 10 Q. Do you know what the storage 11 capacity of that initial Entrex system was? 12 A. No. What do you mean by 13 storage capacity? 14 Q. How many megabytes or how much -- 15 A. Oh, no. 16 Q. Compared to the system that 17 was last used when you left Fluoxetine, is it 18 much -- was it much more improved than what you 19 finally ended up with? 20 A. It was probably state of the 21 art for that period of time, but it was not as 22 sophisticated as what it has grown to be. 23 Q. All right. After you got the 24 computer system set up, what was your next Page 71 1 function in connection with your work as a CRA 2 working on Fluoxetine? 3 A. Then taking the actual case 4 report form data, seeing that it was entered by a 5 group of -- a data entry group of people, and 6 then the information came back on a printout, and 7 worked with checking what was on the case report 8 form with what was on the printout. We didn't 9 have anything to help us do that at that point in 10 time. 11 Q. What did you later have to 12 help you do that? 13 A. Edits. 14 Q. Within the computer? 15 A. Printed out to help you do it. 16 Q. Was there an effort made to 17 put the data that you already had in hard form 18 there in Indianapolis onto this Entrex system or 19 were you simply putting the data that you 20 received once the system was up onto the Entrex 21 system? 22 A. We put the data from HCAC on, 23 so there's some had come in, put that on, and 24 then kept up with what was coming in. Page 72 1 Q. All right. But was all data 2 that you had concerning the clinical trials on 3 the initial Entrex system at some point? 4 A. What are you asking for that I 5 didn't answer, I'm sorry? 6 Q. Well, you told me that HCAC 7 was put onto the Entrex system -- 8 A. Right. 9 Q. -- as it was completed. But 10 as I understand it, there were some studies that 11 had already been completed even before you got 12 there, into the group. My question is: Was that 13 data from those early studies put onto the Entrex 14 system or was it kept in hard form? 15 A. It was in hard form for a 16 while. 17 Q. And then was it later put on 18 some system? 19 A. It was later put on. 20 Q. What system was it put on? 21 A. At that point it was -- okay, 22 as I recall, it was a system thirty-eight. 23 Q. Was that the next system that 24 you used? Page 73 1 A. Yes. 2 Q. All right. We'll get back to 3 that in a minute. How many data entry personnel 4 did you initially start with when you were 5 putting the data onto the Entrex system? 6 A. I don't know because that's 7 another area. 8 Q. You didn't have to worry about 9 the data entry end of it? 10 A. No. 11 Q. So what were you worrying 12 about, what came out of the computer? 13 A. After the design, what came 14 out, and make sure that what was put in is what 15 was on the case report form. 16 Q. What would you do, compare the 17 hard copies of the case report form versus the 18 printed data? 19 A. Yes. 20 Q. By hand? 21 A. Yes. 22 Q. Every day? 23 A. Yes. 24 Q. How much time did that take Page 74 1 every day? 2 A. It would take the majority of 3 the time. 4 Q. Did you have anybody assisting 5 you in doing that? 6 A. Yes. 7 Q. Who? 8 A. Another support person was 9 brought in to help with that. 10 Q. Who was that? 11 A. Shirley Martin. 12 Q. Shirley Martin? 13 A. Uh-huh. 14 Q. She wasn't a CRA? 15 A. No. 16 Q. She was clerical? 17 A. She was an assistant. 18 Q. Assistant clerical or 19 assistant CRA or assistant -- 20 A. How do you define clerical? 21 Q. She didn't have the training 22 where she could have been a clinical research 23 administrator. 24 A. No, she didn't, that's Page 75 1 correct. 2 Q. So now we have -- where are we 3 by the time we get the Entrex system up and 4 running, initially? 5 A. Probably what, '81. 6 Q. Now we have those people 7 working in medical on the Fluoxetine clinical 8 trials, you, Shirley Martin, Paul Stark, and 9 Giselle Soyez. Anybody else? 10 A. No. 11 Q. Four of you. Did I list four? 12 A. Yes. 13 Q. Did I leave anybody out? 14 A. No. 15 Q. Once you got the system 16 thirty-eight up, who were you reporting to? 17 A. Gene Crum. 18 Q. But Gene Crum, as I understand 19 it, wasn't doing any work on Fluoxetine. 20 A. No. 21 Q. What was his title at that 22 time? 23 A. Manager. 24 Q. Manager of what? Page 76 1 A. Medical. I don't know his 2 official title. 3 Q. But did he have any knowledge 4 concerning the Fluoxetine studies? 5 A. No detailed knowledge. 6 Q. He was just your supervisor in 7 connection with seeing that you were there on a 8 daily basis and reviewing your performance 9 evaluations, maybe, is that right? 10 A. Yes. 11 Q. You didn't go to him for any 12 day-to-day advice or recommendations in 13 connection with how you should do your work as a 14 clinical research administrator in connection 15 with Fluoxetine, did you? 16 A. If I talked to him of issues, 17 it wasn't of a, you know, the nature of a study 18 or anything, but I used him as a mentor for 19 understanding the clinical trial process, on 20 issues on how to deal and interact with people 21 and continue to grow and develop. 22 Q. Who were you looking to 23 regularly, though, in connection with answering 24 your questions in how to set this Fluoxetine data Page 77 1 base and study up, Doctor Stark? 2 A. From an input standpoint, 3 working with the systems analyst on how the -- 4 because the study had been designed. So I worked 5 with Giselle and Paul to make sure we were 6 capturing the information, but the actual design 7 and how it was collected, I worked with a systems 8 analyst to develop that. 9 Q. And that was Mister Korteter? 10 A. Korteter. No, that was the 11 first studies going on. 12 Q. And next was Maureen Murray, 13 right? 14 A. Right. 15 Q. You started with three studies 16 or there were three studies ongoing when you 17 began, and the data from those three studies was 18 put onto the Entrex system, is that right? 19 A. Right. 20 Q. What was the next study that 21 was started? 22 A. HCAF. 23 Q. When was that study started? 24 A. I don't remember, that was Page 78 1 phase three, so we were -- I don't remember. 2 Q. Do you remember the protocol 3 number for the HCAF study? 4 A. I think it was protocol 5 twenty-seven. 6 Q. Any other protocols used in 7 the HCAF study? 8 A. Protocol twenty-seven and 9 twenty-eight. Twenty-seven was the double-blind 10 portion of the study, protocol twenty-eight was 11 the extension. 12 Q. What, extension into a 13 compassionate use? 14 A. It was open label. 15 Q. Was the data from the HCAF put 16 onto the study, put onto the Entrex system? 17 A. Yes, it was. 18 Q. How many patients were there 19 in the HCAF study, approximately? 20 A. That was our larger study. 21 Somewhere around five hundred, five plus five 22 hundred. 23 Q. That became a pivotal study, 24 didn't it, protocol twenty-seven, a pivotal Page 79 1 study? 2 A. Yes. 3 Q. Who was the investigator or 4 investigators on protocol twenty-seven? 5 MR. MYERS: Before she answers, let me 6 make the same instruction and check on that. 7 MR. SMITH: She just said it was a 8 pivotal study. 9 MR. MYERS: Right, but I don't know 10 that her understanding of pivotal is the same one 11 that we've been using in this litigation. 12 MR. SMITH: I know protocol 13 twenty-seven was pivotal, and you know that. 14 MR. MYERS: I don't recall if that's 15 one of the ones that we -- we either gave you 16 twenty-seven or twenty-eight, I can't remember. 17 MS. ZETTLER: Twenty-eight was the one 18 that Bob said was not pivotal. 19 MR. MYERS: Hang on for a minute. 20 Q. I believe my question was: 21 What was the name of the investigator on protocol 22 twenty-seven? 23 MR. MYERS: You can tell him. 24 A. There were several, as I Page 80 1 recall. Finer -- 2 Q. Finer? 3 A. Cohn. 4 Q. C-O-N-E? 5 A. C-O-H-N. 6 Q. Oh, C-O-H-N. 7 A. Brumner, Dunner, Gross, 8 Busehab. That's all that I recall. 9 Q. That was pretty good. And 10 that study involved approximately five hundred 11 patients. 12 A. Or more. 13 Q. Well, it wasn't five thousand. 14 A. No. 15 Q. It wasn't a thousand? 16 A. No, no. 17 Q. Probably wasn't seven hundred 18 and fifty, was it? 19 A. I don't recall. 20 Q. When did that study begin and 21 when did it end? 22 A. I don't remember exactly when 23 it began. 24 Q. Approximately? Page 81 1 A. I don't remember when it 2 began. 3 Q. It began after you came on -- 4 A. Yes. 5 Q. -- as a CRA? 6 A. Right. And it had been 7 finished before we submitted for the new drug 8 application. But I cannot recall the exact 9 dates. 10 Q. So the new drug application 11 was submitted in 1983? 12 A. Yes. 13 Q. Or '84? 14 A. '83. 15 Q. When in '83? 16 A. September. 17 Q. So it would have had to have 18 been completed before that because -- 19 A. Yes. 20 Q. -- the results of that study 21 were included in the NDA; correct? 22 A. Right, completed by the end of 23 1982. At least the double-blind portion of the 24 study, so protocol twenty-seven. Page 82 1 Q. Was the data from that study 2 put on the Entrex system? 3 A. Yes. 4 Q. Were the adverse events that 5 were reported during that study put on the Entrex 6 system? 7 A. Yes. 8 Q. Were there any suicides that 9 occurred by patients who were being investigated 10 in that study? 11 A. Not that I recall. 12 Q. Do you know whether or not 13 there were any reports during that study of 14 patients who had attempted suicide? 15 A. Not that I recall. 16 Q. When I say patients, I mean 17 patients enrolled in the study. You understand 18 that, do you not? 19 A. Yes. 20 Q. In connection with that study, 21 were there any adverse events or clinical report 22 forms that reported suicidal ideation occurring 23 in patients involved in that study? 24 A. Not that I recall. Page 83 1 Q. What would I have to do to 2 learn that information? 3 A. What do you mean? 4 Q. Well, that wasn't a good 5 question. What would you need to do in order to 6 see if that occurred? 7 MR. MYERS: Suicidal ideation? 8 Q. Suicidal ideation, whether 9 there were any attempted suicides or any 10 completed suicides during that study. 11 A. If that had happened, it would 12 have been captured in the adverse event section 13 of the case report form. 14 Q. Well, as I understand it, the 15 investigators were given specific instructions 16 concerning how to complete the adverse event 17 section of the case report forms, were they not? 18 A. There were instructions on the 19 case report form that told them how to fill it 20 out. 21 Q. And whether or not a 22 particular situation was classified as an adverse 23 event was something that required some 24 instruction, did it not? Page 84 1 A. I'm not quite sure. 2 Q. Let me give you an example. 3 A. Okay. 4 Q. If someone got sick or became 5 ill while on the study and were hospitalized, 6 that would probably be something that would be 7 mentioned in the adverse event section of the 8 case report form, would it not? 9 A. Yes. 10 Q. All patients who were 11 hospitalized had to be mentioned in the adverse 12 event section; correct? 13 A. If they had an adverse event. 14 Q. That caused hospitalization. 15 A. Right. 16 Q. And if, as I understand it, an 17 individual's depression got worse, that wasn't 18 categorized as an adverse event, was it? 19 A. I would have to look at a case 20 report form page. I mean if the physician wrote 21 it down, it would be captured there. 22 Q. Well, but my point is, if the 23 physician was instructed not to report in the 24 adverse events section of the case report forms Page 85 1 worsening of depression -- 2 MR. MYERS: That's the question? 3 MR. SMITH: Yes. 4 A. And my comment was, to answer 5 your question, I would have to see the case 6 report form to see what it said. 7 Q. All right. You reviewed the 8 investigators brochure? 9 A. Yes. 10 Q. Initially? 11 A. Yes. 12 Q. And you continued throughout 13 your time in your work on Fluoxetine to be 14 reasonably familiar with the investigators 15 brochure, did you not? 16 A. Yes. 17 Q. And doesn't that investigators 18 brochure specifically instruct the physicians, 19 the investigators, on how to complete the case 20 report forms? 21 A. Not the clinical investigators 22 brochure. The protocol tells them how to conduct 23 their study. 24 Q. I understand that, but doesn't Page 86 1 the brochure tell -- give them instructions in 2 how to fill out the form -- 3 A. No. 4 Q. -- how to return materials, 5 and things of that nature? 6 A. Not the clinical investigators 7 brochure that I'm talking about. 8 Q. What is that document that 9 tells the investigator on how to fill out the 10 forms and what the requirements are with respect 11 to returning the forms and securing data in that 12 nature? 13 A. I don't remember the name of 14 that. There is something that is placed in the 15 investigator's office to do those things, I don't 16 remember what it's called, but that's not what 17 I'm talking about when I say clinical 18 investigator brochure, that's strictly the data, 19 what do we know about the drug, does it have any 20 instructions in it. 21 Q. All right. But as one of the 22 original clinical research administrators in 23 connection with Fluoxetine, wasn't it your 24 understanding, based on your recollection, that Page 87 1 the clinical investigators generally were not to 2 report worsening of depression as an adverse 3 event in connection with the drug? 4 MR. MYERS: Let me just object to the 5 form. When you say in connection with the drug, 6 since the study was blinded there may or may not 7 have been a drug or the drug. 8 Q. In connection with the study. 9 MR. MYERS: Better question. 10 MR. SMITH: We always try. 11 MR. MYERS: I know. 12 A. And my answer is I would have 13 to see what the case report form said, or the 14 protocol. At this point, I don't remember that. 15 Q. Do you remember ever, in 16 reviewing the adverse events that occurred during 17 the Fluoxetine studies, seeing worsening of 18 depression as an adverse event? 19 A. Depression was on there as an 20 adverse event, yes. 21 Q. And do you remember worsening 22 of depression as being an adverse event, or 23 increased depression, however -- 24 A. That term would not appear. Page 88 1 Q. Why? 2 A. How you collected the data, it 3 was numerical, so if they had depression, was it 4 mild, moderate or severe, and they checked that. 5 So it wouldn't be depression worsening as an 6 event, it will be depression and then the 7 severity. 8 Q. Well, where on the case report 9 form was there the mild, moderate or severe 10 depression category? 11 A. There wasn't a place to 12 collect that. Talking about the adverse event 13 page, if it was reported, that's where that 14 information would be. 15 Q. And it would have been 16 reported as mild, moderate or severe? 17 A. Any adverse event that was 18 reported, the investigator was asked to say what 19 was the severity of this adverse event. 20 Q. All right. So what you're 21 saying is that there could have been an instance 22 where an investigator reported in the adverse 23 event section increased depression, and then he 24 might have checked two, moderate. Page 89 1 A. He would have said depression, 2 and two. 3 Q. All right. And then it would 4 have been transmitted into your data base as 5 adverse event, depression, two. 6 A. Yes. 7 Q. I think we were diverted there 8 somehow in connection with my original line of 9 questioning, being if I were to or an individual 10 were to look to see whether or not there would be 11 suicide, suicidal ideation, or suicide attempts 12 in the protocol twenty-seven HCAF study, how 13 would they do that? 14 A. See if it was reported on the 15 adverse event page. 16 Q. And would suicidal ideation, 17 according to your understanding, have been 18 reported on the adverse event page? 19 A. Yes. 20 Q. Would it have been reported in 21 any other form in any of the other clinical 22 report forms? 23 A. I don't understand the 24 question. Page 90 1 Q. Well, the adverse event page 2 is just one page -- 3 A. Yes. 4 Q. -- of a number of pages -- 5 A. Right. 6 Q. -- of clinical report forms. 7 Would there have been any other page or indicator 8 of suicide, suicide attempt or suicidal ideation 9 where you would look? 10 A. Any other indicator? 11 Q. Yes. 12 A. The Hamilton Depression Scale. 13 Q. All right. Specifically on 14 the Hamilton Depression Scale, what would you be 15 looking at? 16 A. There were questions -- I mean 17 I don't remember the questions and their numbers, 18 so -- 19 Q. There were questions on what, 20 suicide? 21 A. There were questions on the 22 Hamilton Depression Scale to determine how 23 depressed the patient was. 24 Q. All right. We're talking Page 91 1 about suicide, suicidal ideation or suicide 2 attempts. 3 A. Yes. 4 Q. The Hamilton Depression Scale 5 doesn't record suicides, does it? 6 A. I don't remember. 7 Q. It doesn't record suicide 8 attempts, does it? 9 A. To see the term? I'm having 10 trouble understanding your questions here. To 11 see the term? 12 Q. Yes. 13 A. As I understood your question, 14 where would you find an indication, could find an 15 indication. 16 Q. All right. And you say well, 17 look at the Ham-D. 18 A. That's what I would say. 19 Q. Why would you look at the 20 Ham-D to make a determination with respect to 21 whether or not there was an indication of 22 suicides, to get an indication of whether or not 23 suicides, suicide attempt or suicidal ideation 24 was occurring in a patient during the clinical Page 92 1 studies? 2 A. There are a series of 3 questions to get at how depressed a patient is or 4 how they're feeling at that point in time is what 5 the Ham-D does, and, you know -- that's all. 6 Q. Take your time. 7 A. That's all I can tell you is 8 that if you would get an appraised -- indication, 9 potential indication, the Hamilton's group, when 10 they analyze it -- now, I don't know, I don't 11 recall what all the categories were, or if there 12 was a specific question. You asked me where I 13 would look to get an indication, I gave you my 14 opinion. 15 Q. Anyplace else? 16 A. No. 17 Q. What about the physician's 18 global impressions section? 19 A. I honestly don't recall that 20 being part of the case report forms when I was 21 doing that -- oh, you're talking about the 22 efficacy parameter, which is a scale? 23 Q. Where? 24 A. What are you -- I don't know Page 93 1 what you're talking about. 2 Q. Okay. The efficacy parameter. 3 A. No, I don't think you could 4 tell from that. 5 Q. Anything else in the clinical 6 report forms that would give you an indicator of 7 suicidality occurring in patients? 8 A. Not that I recall. 9 MR. SMITH: Let's take a quick break. 10 (A SHORT RECESS WAS TAKEN.) 11 MR. SMITH: Can you read the last 12 question and answer? 13 (THE COURT REPORTER READ BACK THE 14 REQUESTED TESTIMONY.) 15 Q. Did you have anything to do at 16 all, Ms. Ashbrook, in connection with designing 17 the clinical report forms themselves? 18 A. At that point in time -- 19 Q. Yes, Ma'am. 20 A. -- are we talking about now? 21 Not a lot. 22 Q. What, if any, input did you 23 have in their design? 24 A. The design had been decided Page 94 1 fairly early on, and we continued with those. So 2 the design of the case report forms actually had 3 occurred before I started back in '81. And we 4 continued with that design to collect the data. 5 Q. Well, you said not a lot, 6 which meant to me that you might have had some 7 input. 8 A. That's what I'm saying, at 9 what point in time. At that point in time, as we 10 moved post, then I had more. 11 Q. All right. What was your next 12 input into the design of the case report forms? 13 A. When we moved into the system 14 thirty-eight, in designing some of those studies, 15 but those were post, the studies we're talking 16 about. 17 Q. Post what? 18 A. Post the studies we've been 19 talking about currently. 20 Q. When did the system 21 thirty-eight come on line? 22 A. Oh, boy, probably late '82, 23 early '83, as I recall. 24 Q. I'm trying to, if I can, get a Page 95 1 progressive idea of how your work as a clinical 2 research administrator in the Fluoxetine studies 3 progressed, and I'm trying to -- what I would 4 like to do is get some chronology of the studies 5 that were added, the protocols that were added, 6 the new systems that were put on, the new people 7 that were brought in, try to get through that to 8 get as much information as I can concerning how 9 your job worked. 10 A. But my role was also changing, 11 I didn't remain a CRA. 12 Q. All right. What was your next 13 role then? 14 A. After HCAF -- or where are we 15 from your chronology standpoint? 16 Q. Okay. HCAF would have been 17 completed before September, 1983. 18 A. That's correct. 19 Q. Were there any other studies 20 done other than HCAC, HCAE and HCAF that you were 21 involved in before September of 1983? 22 A. Yes. 23 Q. All right. Tell me about 24 those. Page 96 1 A. HCAD, HCAG, HCAH, HCAI, HCAJ, 2 HCAK. 3 Q. Was HCAD a depression study? 4 A. Yes. 5 Q. Was it a phase two or phase 6 three study? 7 A. Phase two. 8 Q. Do you remember any of the 9 protocols involved in the HCAD study? 10 A. I don't remember the numbers, 11 sorry. 12 Q. You were -- it sounds to me 13 like your brain is set into numbers, I mean into -- 14 A. Into the projects. 15 Q. -- projects as opposed to 16 protocol numbers. 17 A. Yes, that's right. 18 Q. Was HCAD a multi-center study? 19 A. There was more than one 20 investigator. This gets back to our previous 21 conversation where there were -- may have been 22 more than one protocol that went into that 23 project. Each one of the protocols may have been 24 done by an investigator. At this point, I don't Page 97 1 remember if there was more than one investigator, 2 there was at least one investigator, which would 3 mean there was one protocol at that point for 4 that study. 5 Q. No investigator did studies 6 involving more than one protocol, did they, at 7 one time? 8 A. I can't answer that question. 9 Q. You follow what I'm saying? 10 A. Yes. 11 Q. Was HCAD a placebo? 12 A. No. 13 Q. Comparitor? 14 A. No. 15 Q. What's the next category, what 16 would the other categories then be? 17 A. A comparitor, an active 18 comparitor. 19 Q. HCAD wasn't a placebo? 20 A. It wasn't placebo controlled. 21 Q. All right. Was it a -- 22 A. Comparitor. 23 Q. -- comparitor study? 24 A. Yes. Page 98 1 Q. What was the comparitor drug? 2 A. Imipramine. 3 Q. Do you remember how many sites 4 you had on the HCAD study? 5 A. As I indicated, there was at 6 least one investigator. 7 Q. Do you remember the patient 8 population of that study, approximately? 9 A. Small, it was again phase two. 10 Q. Less than a hundred? 11 A. Yes. 12 Q. Less than fifty? 13 A. Probably. 14 Q. Was that study completed 15 before September of 1983? 16 A. Yes. 17 Q. Do you recall whether or not 18 there was any adverse events that occurred during 19 that study involving suicides, suicide attempts 20 or suicidal ideation? 21 A. No, not that I recall. 22 Q. HCAD would not have been a 23 pivotal study, is that right, because there 24 wasn't a placebo arm? Page 99 1 A. That's correct. 2 Q. Do you remember whether or not 3 HCAD involved a specific issue in connection with 4 depressed individuals? 5 A. What -- I don't understand 6 what you mean. 7 Q. Did it involve geriatric 8 patients, did it involve patients with depression 9 in some other disorder, such as obsessive 10 compulsive -- 11 A. No. 12 Q. -- things of that nature? 13 A. No major depressive disorder. 14 Q. Do you recall what the dosage 15 of Fluoxetine involved in that study? 16 A. Yes. 17 Q. What was it? 18 A. Dose titration twenty to 19 eighty. 20 Q. Was that the purpose of the 21 study, to examine the effects of Fluoxetine 22 versus comparitor over various dosage? 23 A. I would have to read the 24 protocol to say specifically. That was the Page 100 1 general design of the study, was dose titration 2 with a comparitor, you know, how do we compare at 3 the end, did the patient get better or not. 4 Q. I would assume each one of 5 these studies were safety and efficacy studies, 6 were they not? 7 A. Yes. 8 Q. HCAG, was that a study that 9 was begun and completed before September of 1983? 10 A. It was begun. I don't know if 11 it would have been totally completed, but it had 12 begun. 13 Q. Was it a placebo or comparitor 14 study? 15 A. It was a comparitor study. 16 Q. What was the comparitor drug? 17 A. I think it was Imipramine, I 18 don't recall for sure. 19 Q. But there was no placebo arm 20 to that study? 21 A. No. 22 Q. How many patients did that 23 study involve? 24 A. It was a smaller study. Page 101 1 Q. Less than fifty? 2 A. Boy. Probably somewhere 3 between fifty and a hundred. 4 Q. What was the purpose of that 5 study? 6 A. It was an inpatient study. 7 Q. Of depressed individuals? 8 A. Major depressive disorder, 9 yes. 10 Q. Any other disorders or axis 11 that went along with the major depressed 12 disorder? 13 A. No. 14 Q. Where was that study done? 15 A. From a city standpoint, I 16 don't know. At this point I can't recall who the 17 investigators were, I think one of them was 18 Davis. 19 Q. Davis? 20 A. I think. I don't know where 21 he's located. 22 Q. Do you recall whether or not 23 in that inpatient study there were any reports as 24 adverse events of suicide, suicidal ideation or Page 102 1 suicide attempts? 2 A. Yes. 3 Q. All right. Were there? 4 A. There was a suicide on the 5 placebo lead-in period. 6 Q. I thought that wasn't a 7 placebo study? 8 A. All studies had a placebo 9 lead-in. 10 Q. Am I confusing that with 11 wash-out period? 12 A. Same as. 13 Q. Placebo lead-in is same as 14 wash-out? 15 A. Yes. 16 Q. Did you make any investigation 17 to determine whether or not that suicide -- that 18 individual who committed suicide was on placebo 19 or on Fluoxetine, or would they have had to have 20 been on placebo? 21 A. They had to have been on 22 placebo, no drug had been administered. 23 Q. This was before any active 24 compound was given to the patient? Page 103 1 A. Correct. 2 Q. And that was an inpatient 3 study? 4 A. Yes. 5 Q. So somebody committed suicide 6 while hospitalized? 7 A. Yes. 8 Q. Any other suicides, suicide 9 attempts or suicidal ideation reported during 10 that study? 11 A. Not that I recall. 12 Q. Was HCAG a phase two or phase 13 three study? 14 A. Phase three. 15 Q. HCAH -- 16 MR. MYERS: Paul, before you go ahead, 17 it's noon, when do you want to break? 18 MR. SMITH: I thought we would work 19 fifteen to thirty more minutes. Is that all 20 right with everybody? 21 MR. MYERS: I've got something -- we 22 can go to 12:15, but I certainly need to do 23 something between the 12:00 and 1:00 o'clock 24 period. Page 104 1 MR. SMITH: Why don't you stop me 2 whenever you need to go. 3 MR. MYERS: That's fine. 4 MR. SMITH: This would be the last and 5 only time I'll let you control the flow of this. 6 MR. MYERS: We'll have to see. 7 MR. SMITH: I'll keep my options open. 8 MR. MYERS: You always do. 9 Q. Was HCAH a placebo study? 10 A. No. 11 Q. Was it a comparitor study? 12 A. Yes. 13 Q. What was the comparitor drug? 14 A. I think it was Doxepin. 15 Q. How many patients were 16 involved in the study, approximately? 17 A. A hundred or less. 18 Q. Was this a multi-center or 19 single-center study? 20 A. I think there were two 21 investigators. 22 Q. Do you recall whether or not 23 there was more than one protocol or only one? 24 A. It was a protocol number with Page 105 1 a protocol number for the extension. 2 Q. What is that protocol number, 3 do you recall? 4 A. Well, let me go through. 5 Probably thirty-one, and then thirty-two was the 6 extension. 7 Q. When you say extension, was 8 that extension to open label? 9 A. Yes. 10 Q. When was it completed? 11 A. It was part of the submission, 12 so it was completed toward the end of '82. 13 Q. When you say part of the 14 submission, what do you mean, it was part of the 15 data that was submitted to the Food and Drug 16 Administration? 17 A. Yes, right. 18 Q. For the NDA? 19 A. Right. 20 Q. When this data is submitted to 21 the Food and Drug Administration, as in your new 22 drug application, is that data all reviewed by 23 the Food and Drug Administration? 24 A. Yes. Page 106 1 Q. As far as you know? 2 A. Yes. 3 Q. Does the Food and Drug 4 Administration consider that data significant? 5 A. What do you mean by 6 significant? 7 Q. Make a determination 8 concerning whether or not to approve the new drug 9 application, to authorize further investigation 10 of the drug? 11 A. It's all reviewed. 12 Q. I mean is this something that 13 the FDA requires that you submit to them, I mean 14 is this something -- this HCAH study, could that 15 have been left out and omitted, the data from 16 that study omitted from the submission? 17 A. No. 18 Q. Why? 19 A. We're getting into 20 regulations. 21 Q. Well, I mean just whatever 22 your understanding is. 23 A. My understanding is when you 24 make a submission, you need to provide to them Page 107 1 all the information that you have on the product 2 up to that point in time, whether it's -- you 3 keep asking about the pivotal studies, or outside 4 of the pivotal studies. They need all that 5 information. 6 Q. Was there any instances of 7 suicide, suicide attempts or suicidal ideation 8 that occurred during that study? 9 A. Not that I recall. 10 Q. Did I ask you when that study 11 was completed -- I think you said it was 12 completed before submission? 13 A. Right. 14 Q. HCAI, was that a placebo only 15 or was that a comparitor study? 16 A. That was also a comparitor 17 study. 18 Q. Was it only a comparitor 19 study? 20 A. You mean was it just 21 Fluoxetine plus a -- 22 Q. Yes. 23 A. Yes. 24 Q. When I say only a comparitor Page 108 1 study, I'm saying that because -- and correct me 2 if I'm wrong, but it was my understanding that 3 there were some studies that had three arms to 4 it, placebo, comparitor and Fluoxetine; is that 5 correct? 6 A. That's correct. 7 Q. But this HCAI was a comparitor 8 only study? 9 A. Yes. 10 Q. And what was the comparitor 11 drug? 12 A. I think it was also Doxepin. 13 Q. What was the purpose of that 14 study? 15 A. I think this one was the 16 geriatric patient population. 17 Q. I forgot to ask you, what was 18 the purpose of HCAH? 19 A. I think it was just a 20 different comparitor for major depressive 21 disorder. The only other thing is I may have -- 22 I may have H and I. If H wasn't the geriatric 23 study, then -- 24 Q. I was. Page 109 1 A. I was. There were two Doxepin 2 studies, and one was geriatric patient 3 population, and the other one was the other 4 population for major depressive disorder. 5 Q. How many patients were 6 involved in HCAI? 7 A. Probably somewhere between 8 fifty and a hundred. 9 Q. Were there any instances of 10 suicide, suicidal ideation or suicide attempts 11 that occurred during that study? 12 A. Not that I recall. 13 Q. How many investigators were 14 there involved in that study? 15 A. Two. 16 Q. Where were they located? 17 A. I don't remember. 18 Q. Do you remember the protocol 19 numbers for that study? 20 A. Well, what did I say HCAI was? 21 Q. Well, you said CAH was 22 thirty-one and thirty-two. 23 A. So this would be thirty-three 24 and thirty-four. Page 110 1 Q. HCAJ, was that a placebo or 2 comparitor study? 3 A. It was neither. 4 Q. What was it then? 5 A. It was QD versus BID, giving 6 Fluoxetine either once daily or twice daily. 7 Q. QID versus BID? 8 A. No, QD is once daily. 9 Q. What was the dosage involved? 10 A. That's -- as I recall, those 11 were all the dose titration studies, but when we 12 got to QD, BID, I don't recall. 13 Q. How many investigators were 14 involved in that study? 15 A. I think there was one. 16 Q. Do you remember where it was 17 located? 18 A. No. 19 Q. Do you remember the patient 20 population? 21 A. Major depressive disorder 22 patients. 23 Q. I'm sorry, number of patients. 24 A. Oh. I think it's in the same Page 111 1 range of fifty to a hundred. 2 Q. Any suicide, suicidal 3 ideations or suicide attempts that occurred 4 during that study? 5 A. Not that I recall. 6 Q. HCAK, what was the nature of 7 that study? 8 A. Weight loss. 9 Q. Was it a placebo study? 10 A. Yes. 11 Q. No comparitor drug? 12 A. No. 13 Q. Was it a pivotal study? 14 MR. MYERS: Let me object to the form. 15 It was a weight loss, it's not been approved for 16 weight loss. How can it be pivotal if there's 17 been no approval, FDA hasn't said. 18 Q. Well, I thought that was the 19 study that you had submitted in your NDA 20 application in 1983? 21 A. Yes. 22 Q. It was studying individuals 23 only with major depressive disorders, was it not? 24 A. The submission? Page 112 1 Q. Yes. 2 A. The indication we were going 3 for, yes. 4 Q. The purpose of the study was 5 to determine whether or not Fluoxetine caused a 6 weight loss, was it not? 7 A. Correct. 8 Q. But you also examined whether 9 or not the individuals who were participants in 10 the study depression got better or worse. 11 A. No. 12 Q. You did not? 13 A. No. 14 Q. They were not given a Ham-D to 15 complete in that study? 16 MR. MYERS: I object to the form, that 17 may be a different question. But if you know, 18 tell him if there was a Ham-D used. 19 A. I don't recall. 20 Q. How many patients were in the 21 study? 22 A. Probably around fifty. 23 Q. How many investigators were 24 used? Page 113 1 A. One. 2 Q. Where was the study conducted? 3 A. I don't know. 4 Q. What were the protocol 5 numbers? 6 A. I don't recall that protocol 7 number. 8 Q. What was the dosage of 9 Fluoxetine used in that study? 10 A. Dose titration twenty to 11 eighty. 12 Q. When was that study completed? 13 A. Before the submission. 14 Q. Was it part of the submission? 15 A. Yes, it was. 16 Q. Was it a pivotal study? 17 MR. MYERS: Same objection as before. 18 Q. Did it -- you can answer that. 19 A. The submission was for major 20 depressive disorder, this was not a study for 21 major depressive disorder. 22 Q. All right. But the 23 individuals that were the subjects of the study 24 were individuals who were suffering from a major Page 114 1 depressive disorder, were they not? 2 A. No. 3 MR. MYERS: No, she answered that a 4 few minutes ago. 5 MR. SMITH: Let her answer it. I mean 6 I may be confused here, Larry. I think you're 7 part of it. 8 MR. MYERS: You are part of it. 9 A. No. 10 Q. Then why did you submit it as 11 part of the submission? 12 A. Again, according to the 13 regulations, you need to submit your data that 14 you have on any patients that have been in a 15 clinical trial. 16 Q. Was there an examination made 17 during that study concerning whether or not the 18 individuals who participated in the studies, 19 major depressive disorder, got better or worse? 20 A. We didn't do that. 21 Q. You didn't analyze that? 22 A. We didn't collect the 23 information. 24 Q. The investigators didn't ask Page 115 1 the individuals whether or not they were getting 2 better or worse in connection with their 3 depression? 4 MR. MYERS: Let me object to the form 5 only because she testified twice earlier that 6 these were not depressed patients. 7 Q. I thought the patient 8 population was major depressive disorders, am I 9 mistaken? 10 A. Not for this study. 11 Q. Okay. So there could have 12 been some non-depressed individuals who were 13 involved in this study? 14 MR. MYERS: I object to the form 15 because you assume that there were depressed 16 patients. She's already said that wasn't the 17 population. 18 Q. Do you remember what the 19 protocol required in connection with whether or 20 not the patients who were to be participants in 21 the study were to be depressed or not depressed? 22 A. I would have to review the 23 protocol. That was not the intent of the study, 24 the intent was weight loss. Page 116 1 Q. I understand that, but do you 2 recall as we sit here whether or not that study 3 included any individuals who were depressed? 4 A. I don't know. 5 Q. Do you recall whether or not 6 there were any instances of suicide attempts, 7 suicides or suicidal ideation that occurred 8 during that study? 9 A. Not that I recall. 10 MR. MYERS: Is this a good point to 11 break? 12 MR. SMITH: Yes. Let me make sure 13 I've got everything. 14 MR. MYERS: Okay. 15 Q. Okay. And you don't recall 16 the protocol number? 17 A. No, I don't. 18 Q. Was there just one protocol 19 used in that study? 20 A. Yes. 21 MR. SMITH: Let's break for lunch. 22 (A SHORT LUNCH RECESS WAS TAKEN.) 23 Q. Ms. Ashbrook, did I understand 24 your testimony this morning that by late '82 or Page 117 1 early 1983, the system thirty-eight was up? 2 A. Yes. 3 Q. And the data was transferred 4 from the Entex -- or Entrex, to the system 5 thirty-eight? 6 A. I didn't say that. 7 Q. All right. How did that work? 8 MR. MYERS: How did what work? Do you 9 want to know if that happened? 10 MR. SMITH: Yes. 11 Q. Did you transfer the data from 12 the Entrex to the system thirty-eight? 13 A. No. 14 Q. Why? 15 A. Because that wasn't where it 16 finally resided, it resided on the host. 17 Q. Could you obtain information 18 from the system thirty-eight that had originally 19 been stored through Entrex? 20 A. No. 21 Q. I really am totally computer 22 illiterate. 23 MR. MYERS: That's what we were 24 talking about when you were out of the room Page 118 1 before. 2 MR. SMITH: I thought you were going 3 to say something offensive. 4 Q. Why would you have two 5 different computers -- is the system thirty-eight 6 and Entrex two different computer systems? Help 7 me. 8 A. It was a different system for 9 entering the data. 10 Q. But the data resided in the 11 same location? 12 A. No. The data -- the final 13 place where the data resides is on the host data 14 base. So a transfer occurs from where it's 15 entered to where you run output on it. 16 Q. But the data location remained 17 the same? 18 A. I don't understand what you're 19 asking. 20 Q. Were you able, regardless of 21 the method, to secure and review data from the 22 Entrex system after you had switched over to the 23 system thirty-eight system? 24 A. Entrex and the system Page 119 1 thirty-eight was a data entry vehicle. 2 Q. All right. 3 A. I put the data in. 4 Q. Neither one of those systems 5 had anything to do with getting it out? 6 A. That's correct. 7 MR. MYERS: You're cooking now. 8 Q. Did you know, Ms. Ashbrook, 9 when you put all this data on your computer 10 system, that you would be able to confuse me 11 fifteen years later? 12 MR. MYERS: That was not a foreseeable 13 happening. 14 A. And I didn't personally put it 15 in. 16 Q. Were there any other clinical 17 trials conducted involving the drug Fluoxetine, 18 for whatever reason, before September, 1983 other 19 than those you have told me about? 20 A. Okay, clinical trials in 21 depressed patients? 22 Q. Any type of patients. The key 23 is involving Fluoxetine, and I'll repeat my 24 question. Were there any other clinical trials Page 120 1 conducted by Eli Lilly and Company, or at their 2 direction, involving the drug Fluoxetine before 3 September, 1983 other than those you've told me 4 about? 5 A. Yes. 6 Q. What were those? 7 A. Clinical pharmacology studies. 8 Q. All right. Were those phase 9 one, two or three studies? 10 A. It would be phase one. 11 Q. Any others? 12 A. The studies that have been 13 completed prior to my getting involved. 14 Q. Are you aware of those 15 studies? 16 A. I'm aware because they're 17 under submission. 18 Q. But those had been completed 19 before you got involved with Fluoxetine? 20 A. Yes. 21 Q. Any other studies that were 22 done? 23 A. There were two other kind of 24 very early exploratory studies. I'm trying to Page 121 1 remember what the indications were. Dystonia, 2 and some other -- I mean it wasn't -- I don't 3 remember what the other indication was, very 4 small. 5 Q. Was the dystonia study done 6 pursuant to a protocol? 7 A. Yes, these were all done 8 pursuant to protocols. 9 Q. Was the dystonia study 10 included in the submission to the Food and Drug 11 Administration? 12 A. Yes. 13 Q. Do you recall whether or not 14 there were any instances of suicide, suicidal 15 acts, suicide attempts or suicidal ideations 16 involved in the dystonia trial? 17 A. Not that I recall. 18 Q. The other trial, you say you 19 cannot recall the subject of that study? 20 A. I want to say myoclonus. 21 Q. Myoclonia? 22 A. Myoclonus. You've got me on 23 the vague recollection. 24 Q. Was that included in the Page 122 1 submission? 2 A. Yes. 3 Q. Were there any instances of 4 suicide, suicidal attempts, suicidal acts in that 5 study? 6 A. Not that I recall. 7 Q. Any other studies done 8 involving Fluoxetine which you're aware prior to 9 September, 1983? 10 A. There was some other studies 11 that had been started in that time frame. 12 Q. Tell me about those studies. 13 A. I think there was one on manic 14 depressive. 15 Q. Do you remember the number of 16 that study? 17 A. No. 18 Q. Do you remember how many 19 patients were involved in that study? 20 A. Probably less than a hundred. 21 Q. Can you tell me when that 22 study began, I think you you said it began around 23 the time of the submission in September of '83, 24 is that right? Page 123 1 A. Yes. 2 Q. And do you recall when that 3 study was completed? 4 A. Not really, no. 5 Q. How many investigators were 6 there involved in that study? 7 A. I don't recall. 8 Q. Did that involve more than one 9 site? 10 A. I don't recall. 11 Q. Do you remember any of the 12 locations? 13 A. No. 14 Q. Do you recall whether or not 15 there were any instances of suicide, suicide 16 attempts or suicidal ideations that occurred 17 during that study? 18 A. Not that I recall. 19 Q. Were there any others started 20 about the time of the submission to the FDA? 21 A. Yes, I think there was one 22 other that had been started at that point in 23 time. 24 Q. Do you recall what the subject Page 124 1 of that study was? 2 A. I think it was AM versus PM. 3 Q. You mean whether or not the 4 medication -- differences in the medication given 5 in the morning versus in the afternoon? 6 A. That's correct. 7 Q. And was that study included in 8 the submission? 9 A. If we had enrolled any 10 patients in that study, from a safety standpoint, 11 those patients would have been included somewhere 12 within the submission. 13 Q. How many patients were in that 14 study? 15 A. Under a hundred. 16 Q. Was this a placebo controlled 17 study? 18 A. I don't recall. 19 Q. Was the manic depressive study 20 a placebo controlled study? 21 A. I don't recall on that one 22 either, sorry. 23 Q. Did either one of those 24 studies, either the manic depressive or the AM Page 125 1 versus PM study, involve the use of comparitor 2 drugs? 3 A. AM versus PM did not, I do not 4 recall. 5 Q. Any instances of suicide, 6 suicidal ideation or suicide attempts on the AM 7 versus PM study? 8 A. Not that I recall. 9 Q. Any other studies done at 10 about this time that you can think of? 11 A. No. 12 Q. How Long did you continue in 13 your job as a clinical research assistant with 14 Fluoxetine? 15 A. In this time frame, I phased 16 from a CRA to a project leader. I don't have 17 specific dates. 18 Q. Can you give me the 19 approximate date that you phased from the CRA to 20 a project leader? 21 A. In the '83-84 time frame. 22 Q. Before you became a project 23 leader, and while you were a clinical research 24 assistant -- Page 126 1 MR. MYERS: Administrator. 2 Q. Administrator. Did you ever 3 hear any discussions concerning any issue with 4 respect to whether or not Fluoxetine 5 Hydrochloride could cause suicidal ideation, 6 suicide attempts or suicide? 7 A. No. 8 Q. Did you ever see any memoranda 9 or inquiry in written form within the Lilly 10 organization concerning whether or not there 11 might be an issue between the relationship of 12 ingestion of Fluoxetine and suicide, suicide 13 attempts and suicidal ideation? 14 A. No. 15 Q. During the time that you were 16 a clinical research administrator, up until 1983 17 and '84, in connection with your work with 18 Fluoxetine, did the issue of whether or not 19 Prozac or Fluoxetine could cause aggressive 20 violent behavior ever arise in any form? 21 A. No. 22 Q. During the time that you were 23 a clinical research administrator, were there any 24 studies done or were there any studies proposed Page 127 1 to examine the issue of whether or not Fluoxetine 2 Hydrochloride could cause or induce suicidal 3 acts, suicides, suicide attempts or suicidal 4 ideation? 5 A. No. 6 Q. During the time that you were 7 a clinical research administrator, was there ever 8 any discussion or proposal concerning doing a 9 study or investigating whether or not ingestion 10 of Fluoxetine Hydrochloride could cause 11 aggressive or violent behavior in individuals 12 consuming Fluoxetine? 13 A. No. 14 Q. By the time you moved from CRA 15 to project leader, how many CRAs were there 16 working on Fluoxetine? 17 A. At least six. 18 Q. Can you name them, please? 19 A. Giselle Soyez, Roberta Smithy -- 20 Q. Smithy? 21 A. Uh-huh. Candy Pearson. 22 MS. ZETTLER: Is that the same as 23 Donna Pearson? 24 THE WITNESS: No. Page 128 1 A. Steve Merten. 2 Q. Did you say Burton? 3 A. Merten, M-E-R-T-E-N. Terry 4 Osborne, and Melissa Au, A-U. 5 Q. You mean Melissa Humbert? 6 A. Yes. 7 MR. MYERS: He's really rolling now. 8 Q. Why were you moved from 9 clinical research assistant to project leader? 10 A. What was your question? 11 Q. Why were you moved or why did 12 you change from clinical research administrator 13 to project leader? 14 A. The medical group was growing 15 so that one manager couldn't really administer 16 and supervise all the people in medical, so they 17 created the role of project leader. 18 Q. And named you to that 19 position? 20 A. I was one of five named, yes. 21 Q. What project were you the 22 leader of? 23 A. Fluoxetine. 24 Q. What Fluoxetine project were Page 129 1 you the leader of? 2 A. Fluoxetine. 3 Q. Total? 4 A. Right. 5 Q. You say there were four or 6 five other project leaders? 7 A. Named within medical. 8 Q. Did any of them have anything 9 to do with Fluoxetine? 10 A. No. 11 Q. They were working on other 12 compounds and drugs? 13 A. Yes. 14 Q. At the time you began as a 15 project leader, how many clinical -- or who was 16 the medical monitor over Fluoxetine clinical 17 trials? 18 A. Paul Stark was. 19 Q. And this was somewhere in '83 20 or '84? 21 A. Yes. 22 Q. Were there any clinical 23 research physicians working on Fluoxetine at that 24 time? Page 130 1 A. No. 2 Q. Doctor Stark is not a medical 3 doctor, is he? 4 A. No. 5 Q. Who were you looking to for 6 support from the medical end in connection with 7 your work on Fluoxetine at the time you began as 8 a project leader? 9 A. I worked with Paul Stark. 10 Q. Did he answer any and all 11 medical questions you had? 12 A. As a project leader, I wasn't 13 asking medical questions. 14 Q. Did any medical questions come 15 up? 16 A. From me? 17 Q. Yes. 18 A. No. 19 Q. Was there a different branch 20 or different department that had the medical 21 staff that was working on Fluoxetine at that 22 time? 23 A. No. 24 Q. Was there a regulatory Page 131 1 department? 2 A. Yes. 3 Q. Who was in charge of the 4 regulatory department at that time? 5 A. Bruce Peck. 6 Q. And as a project leader, with 7 respect to Fluoxetine, you were part of the 8 medical division, not part of the regulatory 9 division, is that right? 10 A. It's all together. 11 Q. All right. I'm lost then. 12 Were there any medical doctors that were 13 overseeing the clinical trials in connection with 14 Fluoxetine? 15 A. Doctor Christianson was in 16 charge of all of medical. 17 Q. Okay. That would be internal 18 medicine -- 19 A. Yes. 20 Q. -- psychiatric medicine, 21 proctology, whatever; correct. 22 A. Yes. 23 Q. Now, was there a medical 24 doctor in charge of Fluoxetine? Page 132 1 A. No. 2 Q. Were there any medical 3 doctors, as far as you know, doing research in 4 connection with medical questions presented by 5 ingestion of Fluoxetine at Eli Lilly when you 6 became a project leader in connection with 7 Fluoxetine? 8 A. Could you -- I'm not tracking 9 with what you're asking. 10 MR. SMITH: Could you read that back? 11 (THE COURT REPORTER READ BACK THE 12 REQUESTED TESTIMONY.) 13 A. I don't understand what doing 14 research means. 15 Q. Research in any fashion. 16 Research on medical questions presented by the 17 clinical trials, research on the biochemistry of 18 Fluoxetine during the clinical trials, research 19 concerning the serotonin reuptake potential 20 properties of the medication, anything. 21 A. Doctor Lemberger at the Lilly 22 clinic did clinical pharmacology studies. 23 Q. What is Doctor Lemberger's 24 first name? Page 133 1 A. Well, we knew him as Lou. I 2 don't know if that is official or it was 3 something else. 4 Q. Maybe Louis? 5 A. Could be. 6 Q. And he was doing 7 pharmacological research? 8 A. What do you mean by that? 9 Q. I thought that's the term you 10 used, pharmacological research? 11 A. I said clinical pharmacology. 12 Q. What kind of clinical 13 pharmacology was he involved in? 14 A. Bioavailability -- it's your 15 phase one studies that you complete for your 16 submissions. Food and fasting, those types of 17 studies. 18 Q. Were there not any -- or were 19 there, at the time you became a project leader in 20 connection with Fluoxetine, were there any 21 medical issues that had been raised by the 22 clinical trials that were being investigated? 23 A. Issues, what do you mean by 24 issues? Page 134 1 Q. Of any nature. 2 A. From the clinical trials? 3 Q. Yes. 4 A. Medical issues? 5 Q. Yes. 6 A. One of the adverse events that 7 we followed to make sure and to watch closely was 8 rash, if a patient developed a rash. 9 Q. Who was the doctor that was 10 examining that issue there in Indianapolis where 11 this data was coming in concerning this rash to 12 make some determination with respect to whether 13 or not this rash was caused by ingestion of 14 Fluoxetine? 15 A. The data that was presented 16 from clinical trials was presented to Paul Stark. 17 Q. All right. 18 A. If he conferred with other 19 physicians, I don't know. 20 Q. I understand that. Who was 21 initially on your team of which you were a leader 22 in connection with Fluoxetine? 23 A. The CRAs that I mentioned. 24 Q. All right. Anybody else? Page 135 1 A. Shirley Martin. 2 Q. Who is Shirley Martin? 3 A. A CIA. 4 Q. CIA? 5 A. Right. She had been mentioned 6 previously today. 7 Q. What does CIA stand for? 8 A. Clinical investigational 9 assistant. 10 Q. Is she the clerical individual 11 we were talking about earlier? 12 A. Yes. 13 Q. Anybody else on your team? 14 A. Betty Lou Emanual. 15 Q. What was her function? 16 A. She was a clerk. 17 Q. Who else was on the Fluoxetine 18 team? 19 A. Barb Bolin. 20 Q. What was she doing? 21 A. She was also clerical. 22 Q. Who else? 23 A. I think that concludes 24 everybody at that time. Page 136 1 Q. You were the first project 2 leader for the first Fluoxetine project team; is 3 that correct? 4 A. What do you mean by project 5 team? 6 Q. Well, if you're a project 7 leader, I assume you are leading a group of 8 individuals, right? 9 A. Yes. 10 Q. Now, is -- and I'm trying to 11 define whether that's the only group of 12 individuals that were working on Fluoxetine other 13 than the clinical investigators in the field. 14 A. We were the group in medical 15 that was working on Fluoxetine, and I was 16 supervising them. 17 Q. What was the function of your 18 group? 19 A. To support the conduct of the 20 clinical trials. 21 Q. Was that the goal of your 22 project? 23 A. How are you defining project? 24 Q. In whatever way you're Page 137 1 defining project in your description of your job 2 as project leader. 3 A. It was all Fluoxetine, it 4 wasn't a single project. It was a single 5 compound, but it wasn't a single project. My 6 role was more of a supervisor. I'm not quite 7 sure what you're after, I'm having trouble. 8 Q. Well, you said that you were 9 broken into a Fluoxetine group, and you were a 10 project leader of that group, is that right? 11 A. Right. 12 Q. The project you've said, as I 13 understand it, was to support the conduct of the 14 clinical trials with respect to Fluoxetine. 15 A. Right. 16 Q. What was the goal of that 17 project? 18 A. It didn't have an end term. 19 Q. Wasn't the goal to secure 20 approval from the Food and Drug Administration to 21 market Fluoxetine as an antidepressant 22 medication? 23 A. That was a milestone, but that 24 wasn't the goal. Page 138 1 Q. Then what was the goal? 2 A. I had indicated the purpose 3 was to support the clinical trials. 4 Q. But the clinical trials were 5 being conducted in an effort to satisfy 6 requirements of the Food and Drug Administration 7 to allow Eli Lilly and Company to market 8 Fluoxetine as Prozac for treatment of depression; 9 is that not correct? 10 A. That's true. 11 Q. And Eli Lilly and Company, as 12 you became a project leader on this team, 13 believed in 1983 or 1984 that that drug would be 14 efficacious in treating depression; is that 15 correct? 16 A. Yes. 17 Q. And that belief supported a 18 number of individuals and a great deal of effort 19 through the clinical trials to support that 20 belief. Was that a question? 21 MR. MYERS: You were doing good for a 22 while, but you broke down at the end. 23 Q. The purpose of the clinical 24 trials was to present data to confirm Lilly's Page 139 1 judgment that Fluoxetine would be efficacious in 2 treating depression; is that correct? 3 A. Yes. 4 Q. And those individuals working 5 on Fluoxetine in 1983 at Eli Lilly and Company 6 believed that that drug would be efficacious in 7 treating depression in 1983, didn't they? 8 A. Yes. 9 Q. But in order for individuals -- 10 for Lilly to market the drug to treat depression, 11 they had to secure Food and Drug Administration 12 approval, didn't they? 13 A. Yes. 14 Q. And in order to get Food and 15 Drug Administration approval, Lilly had to comply 16 with the Food and Drug Administration regulations 17 before they could secure that approval, did they 18 not? 19 A. Yes. 20 Q. And those regulations required 21 that Lilly prove its position with clinical 22 trials, demonstrating safety and efficacy of 23 Fluoxetine, did they not? 24 A. Yes. Page 140 1 Q. And your goal from the time 2 you became project leader was to secure Food and 3 Drug Administration approval of Fluoxetine 4 through compiling all this clinical trial data. 5 A. That's where I think the 6 breakdown is, that's where I'm having trouble, 7 because the submission was made in 1983. 8 Q. All right. But that 9 submission didn't allow Lilly to market 10 Fluoxetine as Prozac, did it? 11 A. That's the package we 12 submitted to the FDA with the data we felt would 13 substantiate the approval of the product. 14 Q. But Lilly wasn't granted that 15 approval until December of 1987, was it? 16 A. That's correct. 17 Q. Lilly didn't make a dime on 18 Prozac until after December of 1987. 19 A. That's correct. 20 Q. Up until December of 1987, all 21 of the money that Lilly spent in connection with 22 research on Fluoxetine for Prozac was on the 23 bottom side of the ledger, wasn't it? 24 A. It was research dollars. Page 141 1 Q. Yes. Research dollars that 2 were not offset until December of 1987 when you 3 had income dollars from the sale of Prozac; 4 correct? 5 A. Yes. 6 Q. From the time of the 7 submission of the NDA to the Food and Drug 8 Administration in September of 1983, you didn't 9 just sit back and wait for approval from the Food 10 and Drug Administration, did you? 11 A. No. 12 Q. As a matter of fact, clinical 13 trial testing increased from September of 1983 14 until December of 1987 when the drug was finally 15 approved by the Food and Drug Administration, 16 didn't it? 17 A. What do you mean by increased? 18 Q. The amount of knowledge and 19 the amount of work expended by Lilly, and the 20 amount of money expended by Lilly, increased from 21 September, 1983 until December of 1987, didn't 22 it? 23 A. I don't know about the dollars 24 spent. Page 142 1 Q. Right. 2 A. We continued to do clinical 3 trials. 4 Q. And tested even more people by 5 December, 1987 than you had until September of 6 1983. 7 A. Yes. 8 Q. The NDA -- the new drug 9 application is an ongoing process, isn't it, Ms. 10 Ashbrook? 11 A. That's where I'm having 12 difficulty understanding. 13 Q. You talk in terms of a 14 submission of an NDA in September of 1983 with 15 respect to Fluoxetine. 16 A. (Witness moves head up and 17 down.). 18 Q. You have to give an audible 19 answer. 20 A. Yes. 21 Q. But that submission didn't end 22 Lilly's work in getting approval of the drug to 23 market to the public, did it? 24 A. No, but it's the amount of Page 143 1 data that we felt and what the FDA reviewed to 2 make a decision if we had a product or did not. 3 Q. Well, are you telling me that 4 the Food and Drug Administration did not examine 5 any data that had been accumulated between 6 September of 1983 and December of 1987 when they 7 granted approval of Fluoxetine for market to the 8 public by Lilly as Prozac? 9 A. We complied with their request 10 for update for safety data. 11 Q. Did you not give them any more 12 efficacy data after September of 1983? 13 A. I can't recall, I know we kept 14 updating the safety data. 15 Q. You understand the distinction 16 between efficacy data and safety data; correct? 17 A. Yes. 18 Q. Do you need a break, I don't 19 want you to fade out on me. 20 A. Yes, if I could have one. 21 (A SHORT RECESS WAS TAKEN.) 22 Q. After the submission in 23 September of 1983, Lilly was continuing to submit 24 safety and efficacy data to the Food and Drug Page 144 1 Administration, were they not? 2 A. According to the regulations, 3 you needed to submit information on an annual 4 basis, with a focus on safety. 5 Q. And Lilly was doing that? 6 A. Yes. 7 Q. And there were ongoing 8 clinical trials that occurred between September, 9 1983 and December, 1987, were there not? 10 A. Clinical trials were started 11 and were ongoing through that period of time, 12 yes. 13 Q. And those clinical trials 14 involved depressed individuals. 15 A. Some of them. 16 Q. And those clinical trials 17 involved treatment of depression with Fluoxetine. 18 A. Some of them, yes. 19 Q. And those clinical trials 20 involved information that would be relevant to 21 the Food and Drug Administration concerning the 22 decision with respect to whether or not to 23 approve Fluoxetine for marketing to the public. 24 MR. MYERS: I object to the form as to Page 145 1 what is or isn't relevant to the FDA. I mean 2 only the FDA can know that. But if you know, 3 tell him. 4 A. I don't. 5 Q. Well, you were submitting 6 information that the Food and Drug Administration 7 was requesting. 8 A. We were complying with the 9 regulations. 10 Q. And to comply with those 11 regulations you had to submit certain data, 12 didn't you, to the Food and Drug Administration? 13 A. Yes. 14 Q. And that data had, I believe, 15 as you earlier expressed, an emphasis on safety, 16 did it not? 17 A. That's correct. 18 Q. The Food and Drug 19 Administration, as far as you know, was not 20 conducting any independent study of Fluoxetine 21 for treatment in depressed individuals before 22 September of 1983, was it? 23 A. I don't understand the 24 question. Page 146 1 MR. SMITH: Could you read it back, 2 please? 3 (THE COURT REPORTER READ BACK THE 4 REQUESTED TESTIMONY.) 5 A. What do you mean by conducting 6 independent studies? 7 Q. Any studies of Fluoxetine in 8 depressed individuals for any reason. 9 A. That the FDA was doing? 10 Q. Yes. 11 A. That they initiated? 12 Q. Yes. 13 A. I didn't know the FDA could 14 initiate studies on their own. 15 Q. Whether they could or not, you 16 don't know that they did, do you? 17 A. No. 18 Q. You don't know of any studies 19 that the Food and Drug Administration ran itself 20 concerning the safety and efficacy of Fluoxetine, 21 do you? 22 A. No. 23 Q. The only studies that you're 24 aware of that were submitted to the Food and Drug Page 147 1 Administration concerning safety and efficacy of 2 Fluoxetine were studies done by Lilly or at 3 Lilly's direction, were they not? 4 A. Yes. 5 Q. Was Eli Lilly and Company 6 continuing to push for Food and Drug 7 Administration approval of Fluoxetine for sale to 8 the public after September of 1983? 9 MR. MYERS: I object to the form and 10 the use of the term push and sale to the public, 11 but answer it if you can. 12 A. I didn't understand what 13 continued to push means. 14 Q. Was everyone at Lilly, as far 15 as you know, hopeful that the Food and Drug 16 Administration would approve Fluoxetine for sale 17 to the public after September of 1983? 18 MR. MYERS: I object to the form, but 19 answer it if you can. 20 A. What do you mean by -- I mean 21 what do you mean by hopeful? 22 Q. Is there something about 23 hopeful that you don't understand, Ms. Ashbrook? 24 A. You replaced that with push. Page 148 1 To me those are two entirely different concepts, 2 so that's why I'm asking you what you mean by 3 hopeful. 4 Q. You were the project leader 5 with respect to Fluoxetine sometime in 6 mid-September. 7 A. Yes. 8 Q. And did you hope that the Food 9 and Drug Administration would approve Fluoxetine 10 for sale by Lilly to the public after that time? 11 MR. MYERS: I object to the form, sale 12 to the public. Answer it if you can. 13 A. I don't understand what you're 14 saying. 15 MR. MYERS: It doesn't matter -- he 16 wants to know if you were hopeful, I think that 17 was basically the question. 18 A. Was I hopeful? 19 Q. Yes. 20 MR. MYERS: That it would get 21 approved. 22 A. Yes. 23 Q. Do you know whether or not 24 there was anybody at Eli Lilly and Company that Page 149 1 you came in contact with that you discussed the 2 matter with that was of the opinion that the Food 3 and Drug Administration should not approve 4 Fluoxetine as submitted in September of 1983? 5 A. No. 6 Q. Why were there studies ongoing 7 after September of 1983 in connection with 8 Fluoxetine in depressed individuals? 9 A. Was that a question? 10 MR. MYERS: Repeat it. 11 (THE COURT REPORTER READ BACK THE 12 REQUESTED TESTIMONY.) 13 A. We were attempting to better 14 understand the drug. 15 Q. Well, was the Food and Drug 16 Administration requiring that Lilly conduct other 17 studies? 18 A. No. 19 Q. Was the purpose of any other 20 clinical studies or clinical trials on Fluoxetine 21 to examine the issue with respect to whether or 22 not Fluoxetine would be useful in treatment of 23 other disorders other than major depression? 24 A. Yes. Page 150 1 Q. What other uses were being 2 investigated for Fluoxetine between the period of 3 September, 1983 up until December of 1987? 4 A. Weight loss, the ones that 5 were already ongoing with AM versus PM, the 6 bipolar disorder, manic depressive. I think we 7 started to look at bulimia, smoking, fixed dose. 8 Q. Were there any other studies 9 after September of 1983 designed to examine the 10 issue of the efficacy of Fluoxetine in treating 11 major depression? 12 A. The fixed-dose studies. 13 Q. All right. Tell me about each 14 one of those, was there more than one? 15 A. The one I remember -- boy, I 16 don't know if it's one study or two studies -- 17 looked at mild depression and major depressive 18 disorder, and used fixed doses of Fluoxetine. 19 Q. What was that study, how was 20 that study characterized, you give me these HCA -- 21 A. I know at that point I was in 22 more of a supervisory role, and my memory, as far 23 as having hands on with that, I don't remember 24 what the study number was. Page 151 1 Q. But it was a fixed-dose study 2 comparing efficacy of Fluoxetine in treatment of 3 major depressive disorders versus milder forms of 4 depression? 5 A. No. Major depressive 6 disorder, in fixed-dose, against placebo, and 7 minor depression, fixed doses, to treat minor 8 depression. 9 Q. When were those studies done? 10 A. Somewhere in that time frame. 11 Q. Between 1983 and 1987? 12 A. They were not completed by 13 then. 14 Q. By 1987? 15 A. They had started, they had 16 started somewhere along that time frame. 17 Q. Along '83, '84, '85? 18 A. No. 19 Q. When did they start? 20 A. Probably -- I'm having trouble 21 recalling in that time frame, '86, '87. 22 Q. When were they completed? 23 A. Probably somewhere late '87, 24 early '88. Page 152 1 Q. Were these multi-center or 2 single-center studies? 3 A. Multi-center. 4 Q. What was the patient 5 population in numbers? 6 A. How many patients were in the 7 studies? 8 Q. Yes. 9 A. It was probably two hundred 10 fifty to five hundred in each one of those 11 segments. 12 Q. Can you give me the location 13 of some of those sites? 14 A. No, I can't. 15 Q. These were placebo controlled 16 studies? 17 A. Placebo was one arm, yes. 18 Q. Was there a comparitor drug? 19 A. No. 20 Q. Were these pivotal studies in 21 the Fluoxetine, Prozac, depression NDA? 22 A. They were not contained within 23 the new drug application because that was 24 submitted in September of 1983. Page 153 1 Q. All right. But the safety 2 data that was accumulated from those trials 3 should have been submitted, should it not? 4 A. Yes. 5 Q. And there would be safety data 6 included in each of those studies because you 7 examine safety each time you do a study. 8 A. That's correct. 9 Q. Were there any reports or 10 mentions during those studies of suicide, suicide 11 attempts or suicidal ideation by individuals who 12 had participated in that study, those studies? 13 A. Not that I recall. 14 Q. How long were you a project 15 leader in Fluoxetine? 16 A. Probably a max of two years. 17 Q. So you started somewhere 18 between '83 and '84, so you would have gone until 19 '85 or '86; is that correct? 20 A. Yes. 21 Q. Who was your supervisor while 22 were you a project leader during that time? 23 A. Gene Crum. 24 Q. Then what was your next job Page 154 1 with Lilly? 2 A. I was named department head. 3 Q. What was the name of that 4 department? 5 A. Medical. 6 Q. You were head of the entire 7 medical department? 8 A. No. 9 Q. Then how did you define the 10 department of which you were a head? 11 A. It wasn't a -- it wasn't an 12 entire department. 13 Q. Okay. What was your group 14 known as? 15 A. It was the Fluoxetine group. 16 Q. Did your duties remain the 17 same as department head of the Fluoxetine group? 18 A. Duties the same as? 19 Q. When you were a project 20 leader. 21 A. It continued with the 22 supervisory role, I got more into recruiting of 23 new people, interviewing people to bring them in, 24 the development of the people so we are Page 155 1 appropriately resourced for what we need to get 2 done. 3 Q. Was department head a new 4 title that would be created? 5 A. Yes. 6 Q. As was project leader? 7 A. Yes. 8 Q. How long were you a department 9 head heading the Fluoxetine group? 10 A. Until the Fall of 1988. 11 Q. Then after the Fall of 1988, 12 what did your job become? 13 A. I became a department head in 14 medical information systems. 15 Q. Did that involve Fluoxetine in 16 any respect? 17 A. No. 18 Q. All right. So the last time 19 you were involved with direct work in connection 20 with Fluoxetine was the Fall of 1988; is that 21 correct? 22 A. That's the last time I've 23 actually supervised the people that were directly 24 involved with it. Page 156 1 Q. But that's not been your last 2 involvement with Fluoxetine, has it? 3 A. Yes. 4 Q. In other words, you didn't 5 have anything to do with Fluoxetine from the Fall 6 of 1988 until Mister Myers called you and said 7 you had to come give your deposition? 8 A. That's correct. 9 Q. Any other studies done on 10 depressed individuals at Lilly? 11 MR. MYERS: During that '83, '87 12 period? 13 MR. SMITH: Yes. 14 A. Not that I can recall. 15 Q. While you were a project 16 leader until approximately '85 or '86, with 17 Fluoxetine, did your duties change or were they 18 increased at any time? 19 A. The size of the group kept 20 growing. 21 Q. What, more CRAs, more clerical 22 people? 23 A. Yes. 24 Q. Then you became a department Page 157 1 head of the medical -- in medical, of the 2 Fluoxetine group in the Fall of 1988 until -- I 3 mean, I'm sorry, in 1985 or 1986, until Fall of 4 1988? 5 A. That's correct. 6 Q. What did your work consist of 7 from '85 to '86 to 1988 while you were the 8 department head of the Fluoxetine group? 9 A. What do you mean what did my 10 work consist of? 11 Q. What did you do? 12 A. I supervised the people, 13 recruited people into the group, kind of the 14 project management, who needed to be working on 15 what, how many people did we need to have on 16 particular studies to be able to get them 17 completed. 18 Q. This is still all exclusively 19 related to Fluoxetine, is it not? 20 A. Yes. 21 Q. What else? 22 A. At that point, I was utilized 23 as a resource to answer questions from what had 24 gone in on the submission, the submission from Page 158 1 Fall of 1983. 2 Q. All right. Anything else? 3 A. A development of people, 4 mentoring them. It was really very 5 administrative. 6 Q. After you became a department 7 head in medical information systems, what was 8 your next job? 9 A. Manager of medical services. 10 Q. And when did you begin and 11 when did you end that? 12 A. March of '90, and through 13 August of '93. 14 Q. Then last August, what did you 15 begin doing? 16 A. Manager of medical business 17 support. 18 Q. What did your job consist of 19 when you were a department head of medical 20 information systems? 21 A. I was responsible for 22 supervising systems analysts, resourcing for the 23 projects we were working on. 24 Q. What projects were you working Page 159 1 on? 2 A. Compounds under study for 3 clinical trials. 4 Q. Nothing to do with Fluoxetine? 5 A. No. 6 Q. We're clear now, you haven't 7 had anything to do with Fluoxetine since the Fall 8 of '98 -- '88, is that right? 9 A. That's correct. 10 Q. Anything else? 11 A. (Witness moves head from side 12 to side.) 13 Q. What was your job as manager 14 of medical services, which you held from March of 15 1990 until August of 1993? 16 A. Medical services comprised 17 medical writing, medical library, medical 18 literature searchers, and medical correspondence. 19 Q. And did that have to do with 20 Fluoxetine? 21 A. My folks could have been 22 responsible, I mean for Fluoxetine. 23 Q. But you didn't do anything 24 with respect to Fluoxetine? Page 160 1 A. No. 2 Q. And what is your job as 3 manager of medical business support? 4 A. I now have the medical 5 writers, which I had previously, I have them 6 again, and a group called data capture 7 coordinators. 8 Q. Capture coordinators? 9 A. Data capture coordinators. 10 Q. Anything else? 11 A. Major project responsibility 12 for reengineering of medical. 13 Q. Medical is being reengineered 14 now? 15 A. We have looked at it, yes. 16 Q. Are you going to do it? 17 A. We're trying. 18 Q. Are they going to make you do 19 it? 20 A. That's on my score card. 21 Q. Who is your current 22 supervisor? 23 A. Greg Johnson. 24 Q. And how long has he been your Page 161 1 supervisor? 2 A. September or October, so a 3 couple of months. 4 Q. What's his title? 5 A. Director of training and 6 planning for medical. 7 Q. What is the drug epidemiology 8 unit, Ms. Ashbrook? 9 A. What is it? 10 Q. What is it. 11 A. It's a group within the 12 company where all spontaneous adverse events come 13 into from around the world, and the clinical 14 trial reports that meet the regulatory criteria 15 are put into -- go into the drug epidemiology 16 unit for capture in the system. 17 Q. Have you ever had anything to 18 do with the drug epidemiology unit? 19 A. Yes. 20 Q. When? 21 A. My responsibilities shifted 22 when I was in medical services. 23 Q. When you were a manager of 24 medical services? Page 162 1 A. Yes. 2 Q. What do you mean your 3 responsibility shifted? 4 A. Well, I started out -- you 5 said what did I start out with, medical writing, 6 and medical correspondence, and the library, and 7 literature searching people. At that time we 8 were reporting up through medical regulatory, and 9 we made a kind of shift in responsibilities 10 between the managers, and I lost the medical 11 writers and picked up the drug epidemiology unit. 12 Q. When did you have the drug 13 epidemiology unit? 14 A. Somewhere along the line of 15 '91, I picked it up. 16 Q. Until when? 17 A. Until -- 18 Q. August of '93? 19 A. Yes, August of '93. 20 Q. Well, you did a lot of work 21 with Fluoxetine in your capacity as head of the 22 DEU, didn't you, Ms. Ashbrook? 23 A. No. I personally was not 24 involved in what happened. Page 163 1 Q. Didn't you oversee that unit? 2 A. I had a department head that 3 oversaw the unit. 4 Q. Who was the department head? 5 A. Melissa Humbert. 6 Q. Weren't you involved in the 7 assimilation and compiling of a lot of data on 8 reports of adverse reactions to Prozac -- 9 A. No. 10 Q. -- that would come in? 11 A. I personally, no. 12 Q. You don't have any knowledge 13 of that data? 14 A. No, not really. 15 Q. Did you ever review that data 16 to see that that data was accurate concerning the 17 amount and number of adverse experiences and 18 adverse reactions with Prozac was active? 19 A. No. 20 Q. Did you ever work with any of 21 the medical clinical research physicians in 22 evaluating whether or not a particular adverse 23 reaction was attributable to Fluoxetine? 24 MR. MYERS: Let me object to the form Page 164 1 and the term reaction, Paul, because that assumes 2 there is a relationship. You had it right 3 before, you said experience. 4 MS. ZETTLER:. The FDA uses adverse 5 drug reaction, and they don't assign any causal 6 relationship to it. 7 MR. MYERS: She can answer, I object 8 to the form. 9 A. Now I have lost track. 10 MR. MYERS: I think he wanted to know 11 if you reviewed the things with the physician. 12 A. With the physicians? 13 MR. SMITH: Read the question back to 14 her. 15 (THE COURT REPORTER READ BACK THE 16 REQUESTED TESTIMONY.) 17 A. In what time frame? 18 Q. While you were the head of the 19 drug epidemiology unit, Ms. Ashbrook. 20 A. I wasn't head -- I was the 21 manager of the group, I was not the department 22 head. And no, I did not. 23 Q. Well, while you were the 24 manager of the drug epidemiology unit, you bore Page 165 1 responsibility, did you not, for the workings of 2 the drug epidemiology unit? 3 A. What do you mean by bore 4 responsibility for the workings of? 5 Q. You had to account to your 6 supervisor concerning the conduct of that unit, 7 did you not? 8 A. Yes. 9 Q. It was your responsibility, 10 wasn't it? 11 MR. MYERS: It, unit? 12 MR. SMITH: The drug epidemiology 13 unit. I think she understood what I was talking 14 about. 15 A. It was my responsibility, from 16 administration of the group, to see that proper 17 training was provided, that we had the 18 appropriate type of personnel brought into the 19 unit. I mean that was my biggest contribution, 20 that they understood what they were doing. The 21 department head followed up from a mentoring 22 standpoint with what was going on, and had a lot 23 closer daily contact with the group. 24 Q. But that department head had Page 166 1 to report to you -- 2 A. Yes. 3 Q. -- concerning the activities 4 in that group, didn't he? 5 A. Yes. 6 Q. And if there was something 7 wrong in that group, you held your department 8 head responsible for overseeing and correcting 9 that problem, didn't you? 10 A. If there was a problem, I 11 don't know what you mean by problem. 12 Q. Whatever. I'm not trying to 13 imply anything sinister in that, but if there was 14 a problem, you expected your department head to 15 take care of that; correct? 16 A. Yes. 17 Q. And you held him accountable 18 for that, did you not? 19 A. Yes. 20 Q. Conversely, your supervisor, 21 who was at that time -- 22 A. Max Talbott. 23 Q. -- Max Talbott, looked to you 24 to ensure that that -- Page 167 1 A. Right. 2 Q. -- unit was working properly, 3 did he not? 4 A. Yes. 5 Q. And he looked to you to solve 6 or correct any problems that might be occurring 7 within the drug epidemiology unit. 8 A. I'm not sure what you mean by 9 solve any problems. 10 Q. Making sure the unit was 11 running as it should be. 12 A. Running as it should be, 13 meaning? 14 Q. Obtaining the information that 15 it was designed to obtain. 16 A. Yes. 17 Q. And is it your testimony that 18 while you were the manager of the drug 19 epidemiology unit from 1991 until August of 1993, 20 you didn't work on any projects or solve any type 21 of situation that arose in the drug epidemiology 22 unit concerning Fluoxetine and adverse 23 experiences dealing with Fluoxetine that were 24 reported and collected by the drug epidemiology Page 168 1 unit? 2 A. I mean, did you mean did I get 3 involved in the data? 4 Q. In any respect. 5 A. I saw when there were projects 6 that needed support, we had the people on it to 7 support it. 8 Q. Ms. Ashbrook, are you aware 9 that there's an issue in this lawsuit concerning 10 whether or not Fluoxetine causes suicide, 11 suicidal acts, suicide attempts and suicidal 12 ideation in individuals? 13 A. Am I aware that this case is -- 14 Q. Yes. 15 A. From what I have heard, yes. 16 Q. Had you ever heard that at 17 Lilly in any capacity before you were advised to 18 come give your deposition here today? 19 MR. MYERS: That suicide was an issue 20 or that it was an issue in this case? 21 Q. That suicide was an issue in 22 connection with the drug Prozac, the compound 23 Fluoxetine, Lilly one one one oh nine, or 24 whatever it is. Page 169 1 MR. MYERS: That's a different 2 question, but go ahead and answer that if you 3 can. 4 A. I was aware from listening in 5 meetings of what was going on, that there were -- 6 from spontaneous reports, we were getting reports 7 of suicide, suicide attempts. 8 Q. When did this first come up 9 that you recall? 10 A. It was -- when it first came 11 up, I don't think I had the unit. 12 Q. I don't understand. You mean 13 the drug epidemiology unit? 14 A. Right. 15 Q. Regardless of where you were. 16 Let's put the drug epidemiology unit aside for a 17 minute. I want to go to the question of when you 18 first became aware that there might be an issue 19 that Fluoxetine was causing people to commit 20 suicide, attempt suicide or engage in suicidal 21 ideation? 22 A. I mean what do you mean by an 23 issue? 24 Q. Whether or not it could be Page 170 1 occurring. 2 A. I'm not sure when that became 3 an issue. 4 Q. When do you recall first 5 recognizing it as an issue? 6 A. I don't know that I recognized 7 it as an issue. 8 Q. Whether you believed it or 9 not, when do you remember it first being 10 discussed by somebody at Lilly as a potential 11 issue? 12 A. I'm not -- when did I first 13 hear of it? 14 Q. Yes. 15 A. I don't recall. 16 Q. Well, was it when you were a 17 clinical research administrator? 18 A. No. 19 Q. Was it when -- you were a 20 clinical research administrator until 1983 or 21 1984; correct? 22 A. Right. 23 Q. Was it when you were a project 24 leader? Page 171 1 A. No. 2 Q. When Fluoxetine -- it never 3 came up when you were a project leader, the issue 4 of Prozac and suicidality? 5 A. No. 6 Q. And you were a project leader 7 until 1985 or '86; correct? 8 A. Correct. 9 Q. Did the issue of Prozac and 10 suicidality come up when you were the department 11 head of medical, heading up the Fluoxetine group -- 12 A. No. 13 Q. -- from 1986 until 1988? 14 A. No. 15 Q. It never came up during that 16 period of time? You've never heard of it, never 17 been an issue as far as you know? 18 A. No. 19 (PLAINTIFFS' EXHIBIT NO. 1 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 Q. Have you had an opportunity to 23 look at that document? 24 A. Yes. Page 172 1 Q. Ms. Ashbrook, I've handed you 2 a document that the court reporter has marked as 3 Exhibit 1. What is the date of that document? 4 A. It says June 24, 1985. 5 Q. Is your name on that document? 6 A. Yes, it is. 7 Q. Can I point out something to 8 you on that document. What is that document? 9 A. Final review of Fluoxetine 10 international product monograph or a B form. 11 Q. Do you have a recollection of 12 seeing that document before? 13 A. I don't recall it. 14 Q. Do you know what the 15 Fluoxetine international product monograph is? 16 A. I don't know what it's 17 referring to, I mean I don't recall Fluoxetine 18 international product monograph. 19 Q. You know what a Fluoxetine 20 product monograph is, don't you? 21 A. Yes. 22 Q. And you know what 23 international is, don't you? 24 A. Yes, I do. Page 173 1 Q. All right. So based on your 2 knowledge of those two things, tell me what your 3 best judgment is concerning what a Fluoxetine 4 international product monograph is? 5 A. I remember we created a 6 Fluoxetine product monograph. 7 Q. Were you involved in the 8 creation of that monograph? 9 MR. MYERS: The one to which she 10 refers or to which this refers? 11 MR. SMITH: Either one. 12 A. And I don't recall if it's one 13 and the same. 14 Q. You recall the one you were 15 involved in. 16 A. I was involved probably from a 17 review standpoint at this time. We had 18 physicians involved that pulled this together, 19 working with medical writing. I was not hands 20 on. 21 Q. All right. You were not hands 22 on, Ms. Ashbrook, in June of 1985. At that time 23 you were either the Fluoxetine group leader, 24 project leader -- yes, you would have been the Page 174 1 Fluoxetine project leader. Is it your testimony 2 now that you weren't involved in the hands on 3 dealings with this medication? 4 MR. MYERS: I object to the form, 5 that's not what she said. 6 A. When I became project leader, 7 I focused more on supervision of the personnel, I 8 was not hands on, day-to-day, with the data of 9 Fluoxetine. 10 Q. You were the leader of the 11 Fluoxetine project, though, weren't you? 12 A. For medical support. 13 Q. Your designation wasn't 14 project leader for medical support for 15 Fluoxetine, was it? 16 A. This gets back to the question 17 what do you mean by project leader. 18 Q. You defined it, it was your 19 term, wasn't it? 20 A. It was a term that was given 21 to us before they created department heads. 22 Q. Fluoxetine -- you were the 23 project leader of Fluoxetine, we covered that ad 24 nauseum, this morning, didn't we? This is one of Page 175 1 the reasons I wanted to cover it, is were you not 2 the project leader of Fluoxetine in June of 1985 3 when that Exhibit 1 was dated? 4 A. Yes. 5 Q. All right. And are you not 6 listed number two on that list of individuals of 7 probably thirty individuals? 8 A. It's listed alphabetically. 9 Q. You're listed alphabetically 10 as the number two individual, are you not? 11 A. Yes. 12 Q. You're listed there with 13 Doctor Max Talbott, aren't you? 14 A. Yes. 15 Q. He's what, he was what at that 16 time? 17 MR. MYERS: You want to know what 18 Talbott's position was at the time? 19 MR. SMITH: Yes. 20 MR. MYERS: As opposed to who's what 21 at that time? Tell him what Talbott's position 22 was at that time. 23 A. He was in regulatory. 24 Q. He was the head of regulatory, Page 176 1 wasn't he? 2 A. I guess. 3 Q. Wasn't the NDA submitted under 4 his name? 5 A. No. 6 Q. And whose name was it 7 submitted? 8 A. Doctor Dobbs. 9 Q. But didn't Doctor Talbott sign 10 the new drug application that was submitted in 11 September of 1983 to the Food and Drug 12 Administration as being the individual at Eli 13 Lilly and Company that was responsible or liaison 14 between Eli Lilly and the Food and Drug 15 Administration in connection with any issue that 16 came up with the drug under consideration? 17 A. I don't know, I didn't think 18 he was. 19 Q. All right. Doctor R. L. Zerbe 20 is listed on Plaintiffs' Exhibit 1 also, is he 21 not? 22 A. Yes. 23 Q. Doctor Zerbe was extremely 24 instrumental in the development and organization Page 177 1 of Fluoxetine, was he not? 2 A. He was our medical director at 3 the time. 4 Q. Doctor W. L. Thompson's name 5 is on that list also, isn't it? 6 A. As a CC. 7 Q. Doctor Thompson received a 8 copy of that, did he not? 9 A. I would assume so. 10 Q. Who is Doctor Thompson now, 11 Doctor Leigh Thompson? 12 A. I can't tell you what his 13 title is now. 14 Q. Well, isn't he chief 15 scientific officer? 16 A. Okay, yes. 17 Q. For the entire Eli Lilly and 18 Company? 19 A. Yes. 20 Q. What was he then, what was his 21 title then? 22 A. Like executive director of 23 medical. 24 Q. Do you see, Ms. Ashbrook, Page 178 1 there in -- under the term clinical, under the 2 clinical safety portion of that document, do you 3 see that, where I'm reading? 4 A. Yes. 5 Q. There, that document dated 6 June 24th, 1985, indicates that new sections on 7 long-term safety laboratory data and suicides was 8 being included in the clinical safety part of the 9 final review of Fluoxetine international product 10 monograph; is that correct? 11 A. That's what it says. 12 Q. All right. Were you not aware 13 that suicides in connection with Fluoxetine was 14 an issue in June of 1985? 15 MR. MYERS: Hold on. I object to the 16 form because you're trying to equate what that 17 exhibit says with your question, which may well 18 be two different things. But if you know, tell 19 him. 20 A. As I answered, I did not 21 recall. 22 Q. I thought you said you had 23 heard nothing concerning the relationship or an 24 issue with respect to suicide and Fluoxetine Page 179 1 until well after the Fall of 1988 when you became 2 a department head with medical information 3 systems. Was I mistaken in that, Ms. Ashbrook? 4 A. That's what I said. 5 Q. Is that correct? 6 A. That exhibit indicates that it 7 was previously, I did not recall it. 8 Q. Your name is on that exhibit? 9 A. I see. 10 (PLAINTIFFS' EXHIBIT NO. 2 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Would you review for me, Ms. 14 Ashbrook, a document marked Plaintiffs' Exhibit 15 2? 16 A. I'm sorry, what was your 17 question? 18 MS. MYERS: He wants you to review 19 that. 20 Q. I want you to be able to be 21 familiar with it before I ask you any questions 22 concerning it, Ms. Ashbrook. 23 A. Okay. 24 Q. What's the date of that Page 180 1 document? 2 A. June 2Oth, 1985. 3 Q. Is your name on that document, 4 Ms. Ashbrook? 5 A. Yes. 6 Q. At that time were you the head 7 of the medical group in charge of Fluoxetine? 8 A. As department head? 9 Q. Yes. 10 A. Yes. 11 Q. Your name is listed first on 12 that document, is it not? 13 A. Yes, because they're listed 14 alphabetically. 15 Q. That's a document from a 16 J. H. Potvin, is it not? 17 A. Yes. 18 Q. J. H. Potvin was under your 19 supervision in June of 1985. 20 A. No. 21 Q. When did J. H. Potvin come 22 under your supervision? 23 A. In 1990 when I became manager 24 of medical services. Page 181 1 Q. You eventually became Potvin's 2 boss, didn't you? 3 A. Yes. 4 Q. All right. That document has 5 you listed number one on it, does it not? 6 A. Yes. 7 Q. It has again Doctor Zerbe -- 8 A. Yes. 9 Q. -- as copied. It has Doctor 10 Talbott, the head of the regulatory affairs at 11 that time, does it not? 12 A. Yes. 13 Q. Has Doctor Lemberger's name on 14 it, does it not? 15 A. Yes. 16 Q. Doctor Lemberger was the head 17 doctor at Lilly at the time, wasn't he? 18 MR. MYERS: I object to the term head 19 doctor. 20 Q. He was the doctor that was in 21 charge of the medical group overseeing all the 22 clinical trials, wasn't he? 23 A. No. 24 Q. Who was he then? Page 182 1 A. He was at the Lilly clinic. 2 Q. All right. That document is a 3 review of Fluoxetine clinical investigation 4 manual on depression, wasn't it? 5 A. Yes. 6 Q. You were familiar with that 7 clinical investigation manual, weren't you? 8 A. Yes. 9 Q. You in fact contributed to 10 that manual, didn't you, Ms. Ashbrook? 11 A. What do you mean by 12 contributed? 13 Q. Had input into the contents of 14 that document. 15 A. I was probably one of the 16 reviewers. 17 Q. So you had input into the 18 contents of that document, did you not? 19 A. I was a reviewer. 20 Q. Exhibit 2 is dated June of 21 '85, and it mentions suicide too, doesn't it? 22 A. Yes. 23 Q. Read what it mentions about 24 suicide. Page 183 1 A. It said that it's from the B 2 form. So whatever was written in the B form was 3 put in here, the exact same sections. Reviewer's 4 changes have been incorporated and new 5 subsections on long-term safety, laboratory data 6 and suicide is added. 7 Q. In 1985 they were adding to 8 the clinical safety portion of the clinical 9 investigators manual, weren't they? 10 A. Yes. 11 Q. And in 1985 they were adding 12 sections on suicide, weren't they? 13 A. That's what it says. 14 Q. And you were listed on that 15 document that says that. 16 A. Yes. 17 Q. And that document is dated 18 June 18th, 1985, isn't it? 19 MR. MYERS: Yes, we've established 20 that for about the third time. 21 Q. Isn't it? 22 A. June 20th. 23 MR. MYERS: There's two dates. 24 A. Whoever got it, that's when Page 184 1 whoever got it. 2 Q. It's dated June 18th, isn't 3 it? 4 A. Yes. 5 Q. So the issue of suicide was 6 coming across your desk at least in June of 1985. 7 MR. MYERS: I object to the form. 8 Q. Correct? 9 MR. MYERS: Answer it if you can. 10 A. From those documents -- from 11 those memos, it said, yes. 12 Q. Do you read the memos that are 13 sent to you, Ms. Ashbrook? 14 A. Most of them, if I have time. 15 Q. Would you have disregarded the 16 Fluoxetine clinical investigation manual on 17 depression? 18 A. No. 19 Q. Would you have disregarded 20 that section on this document that talks about 21 clinical safety? 22 A. No. 23 Q. When did Doctor Wernicke take 24 over as medical monitor with respect to the Page 185 1 Fluoxetine clinical trials? 2 A. Probably in the '84, '85 time 3 frame. 4 Q. He was the medical monitor in 5 July of 1986, was he not? 6 A. I can't recall the specific 7 dates. I would think so. 8 (PLAINTIFFS' EXHIBIT NO. 3 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. Have you had an opportunity to 12 review Plaintiffs' Exhibit 3, Ms. Ashbrook? 13 A. No, I just received it. 14 Q. I'm sorry. 15 MR. MYERS: She's looking at it. 16 A. Okay. 17 Q. Can you identify Plaintiffs' 18 Exhibit 3? 19 A. It's a memo, July 2nd, 1986, 20 entitled field audit of Fluoxetine HCDD, protocol 21 seventy-nine. 22 Q. Your name is on that document, 23 is it not, Ms. Ashbrook? 24 A. As a CC, yes. Page 186 1 Q. That means you got it, didn't 2 it? 3 A. Yes. 4 Q. It's dated July 12th, 1986, 5 isn't it? 6 A. Yes. 7 Q. That memo discusses the issue 8 of suicide, does it not? 9 A. It talks about a patient in a 10 study. 11 Q. Yes. 12 A. That had made prior -- with 13 prior suicide attempts. 14 Q. And there was an issue of 15 whether or not that patient should be included in 16 the study, wasn't there? 17 A. There was a question with 18 respect to that. 19 Q. Right. There was a question 20 that the medical monitor, Doctor Wernicke, who 21 is, by the way, a medical doctor, is he not? 22 A. Yes, he is. 23 Q. And he was the medical monitor 24 at the time, was he not? Page 187 1 A. Yes, he was. 2 Q. And he is discussing whether 3 or not a patient who had engaged in prior suicide 4 attempts should be allowed in a clinical study 5 involving depressed individuals, wasn't he? 6 A. That was the question from the 7 field audit. 8 Q. And that's the answer he's 9 trying to give, too, isn't it? 10 A. Yes. 11 Q. And he's talking there about 12 the Ham-D Depression Scale, isn't he? 13 A. He's talking about that. 14 Q. And he expresses the opinion 15 in that document that the Ham-D item three is not 16 a -- 17 A. It doesn't say that, it says 18 suicide fact on the Ham-D does not provide an 19 accurate predictor. It doesn't indicate. 20 Q. Did I say Ham-3, I meant 21 Ham-D. He expresses the opinion that the Ham-D 22 is not an accurate predictor of future suicidal 23 behavior, doesn't he? 24 A. That's what it says. Page 188 1 Q. So there were documents coming 2 across your desk in 1986 discussing the issue of 3 the Hamilton Depression Scale, and whether or not 4 it was an accurate measure and predictor of 5 suicidal behavior, wasn't there? 6 A. This came across my desk. 7 Q. Did you read it? 8 A. At the time. 9 Q. Have you just forgotten that 10 that was a subject of inquiry back in 1986? 11 A. I guess I have -- as you term 12 issues, I think of them as, you know, your 13 definition of issues versus an inquiry to me. 14 This says that people that are depressed, you 15 know, may have had prior suicide attempts, should 16 they have been allowed into the study. As is 17 true with many issues in the treatment of complex 18 disease, this is really a judgment call of the 19 investigator. Again, we felt it was an issue or 20 it was the investigator's judgment whether 21 patients should be enrolled in these studies. I 22 obviously, from the comments today, did not 23 interpret it as an issue. 24 Q. That's probably because you Page 189 1 had drawn a foregone conclusion in 1986 2 concerning whether or not Prozac could cause 3 someone to become suicidal. 4 A. No. 5 Q. You had not? 6 A. (Witness moves head from side 7 to side.). 8 Q. You hadn't come to a 9 conclusion in that respect in June of 1986? 10 A. We're in research. In 11 research you continue to gather data and you keep 12 an open mind. 13 Q. All right. The submission to 14 the Food and Drug Administration was submitted in 15 1983, was it not, September of 1983? 16 A. Yes. 17 Q. But you were having to 18 continue to send in safety data regularly, were 19 you not? 20 A. Yes. 21 Q. And if it concerned a serious 22 adverse event, a 1639 had to be reported to the 23 Food and Drug Administration and reported within 24 a much shorter time period, did it not? Page 190 1 A. Yes. 2 Q. When was the application made 3 to the country of Germany for approval of 4 Fluoxetine for depressed individuals in Germany? 5 A. When was it submitted in 6 Germany? 7 Q. Yes. 8 A. I don't know. 9 Q. Was it before or after 10 submission to the Food and Drug Administration in 11 the United States of America in September of 12 1983? 13 A. It was -- I'm pretty sure it 14 was after. 15 Q. After. 16 A. Yes. 17 Q. Let me see if I understand how 18 this works. Lilly completed their submission to 19 the Food and Drug Administration in September of 20 1983; is that correct? 21 A. Yes. 22 Q. And at the time of that 23 submission in September of 1983, it was Lilly's 24 position that Fluoxetine would be a safe product, Page 191 1 and would be an efficacious treatment for 2 individuals with depression; is that correct? 3 A. That's correct. 4 Q. In other words, the NDA 5 submission in September of 1983, in Lilly's 6 position, was a compilation of data that 7 supported its position that Prozac, Fluoxetine, 8 was safe and efficacious in treatment of 9 depression, is that right? 10 A. It was a compilation of all 11 the data we had gathered to date. 12 Q. And it was Lilly's scientists' 13 conclusion that that data established 14 conclusively safety and efficacy that would 15 warrant Food and Drug Administration approval of 16 the drug. 17 A. Yes. 18 Q. Then after that, Lilly 19 submitted information to the country of Germany 20 and requested that their regulatory authorities 21 allow you to sell that product to the citizens of 22 Germany? 23 MR. MYERS: I object to the form of 24 the question on sell it to the citizens anywhere. Page 192 1 MR. SMITH: Oh, come on, Larry, we're 2 going to be here all day. 3 MR. MYERS: Then ask the question the 4 right way. 5 Q. What I mean is allow the 6 doctors in Germany to prescribe that medication 7 for German citizens. 8 A. We provided to our German 9 affiliate what they wanted from the U.S. 10 submission. 11 Q. All right. Was the German 12 government, as far as you know, submitted the 13 same data as was submitted to the Food and Drug 14 Administration? 15 A. I don't know what our German 16 affiliate submitted to the BGA. 17 Q. Do you know what the German 18 affiliate requested of Lilly? 19 A. I know -- I mean I don't know 20 off the top of my head, but they told us what 21 sections they wanted, and we provided it to them. 22 Q. Did you provide them all your 23 safety data? 24 A. I don't recall. Page 193 1 Q. Do you recall withholding any 2 safety data? 3 A. I don't recall. 4 Q. Would you have withheld any 5 safety data from submission to the German 6 authorities? 7 A. Would I have personally done 8 that? 9 Q. Yes. 10 A. No. 11 Q. Would you have allowed anybody 12 under your supervisory control to do that? 13 A. One of my CRAs? 14 Q. Yes. 15 A. No. 16 Q. The fact that there's -- well, 17 let me ask you this: Do you know whether or not 18 more or less data is required by the German 19 government than that data is required from the 20 Food and Drug Administration? 21 A. What do you mean by more data? 22 Q. Safety data, in connection 23 with an application in order to -- 24 A. What do you mean by more Page 194 1 safety data, you mean numbers of patients or more 2 tests or -- I don't know what you mean. 3 Q. What I'm wanting to know is 4 would a foreign government get less or more 5 information than the Food and Drug Administration 6 got in the September, 1983 submission? 7 A. We met with the regulatory 8 people from our affiliates, they knew what the 9 regulatory requirements were for their countries, 10 they told us what they wanted, that's what we 11 provided. 12 Q. All right. Was there anything 13 that they requested that you did not provide? 14 A. That we could not provide? 15 Q. That you did not provide. 16 A. Oh. No, if they requested it, 17 if we had it, we provided it. 18 Q. Would that information, had it 19 dealt with safety, been the same information that 20 would have been presented to the Food and Drug 21 Administration? 22 A. That's what would have been 23 received by our affiliate from us. 24 Q. Do you recall suicide being a Page 195 1 concern of the German regulatory authorities? 2 A. I recall that we received 3 numerous questions from the BGA. 4 Q. Is that the German regulatory 5 authority? 6 A. Yes, sorry. At this point, I 7 don't remember what all the issues were. 8 Q. We're going to help you. 9 (PLAINTIFFS' EXHIBIT NO. 4 WAS 10 MARKED FOR IDENTIFICATION AND 11 RECEIVED IN EVIDENCE.) 12 Q. Ms. Ashbrook, have you had an 13 opportunity to review Exhibit 4? 14 A. Yes. 15 Q. That document is dated June 16 26th, 1984, is it not? 17 A. Yes, it is. 18 Q. At that time you were the 19 project leader in the Fluoxetine group, were you 20 not? 21 A. Yes. 22 Q. The document is in fact 23 directed to you and C. D. Hardison and Doctor 24 Stark. Page 196 1 A. Yes. 2 Q. Is that correct? And you are 3 listed first in that group of addressees. 4 A. Because it's alphabetical. 5 Q. And then there's a lot of 6 individuals copied onto that document, is there 7 not? 8 A. Yes. 9 Q. The document is sent from 10 Germany, isn't it? 11 A. Yes. 12 Q. And it's sent by a J. Schenk, 13 is that right? 14 A. That's what it says. 15 Q. Who is J. Schenk, S-C-H-E-N-K? 16 A. She is in the German 17 affiliate. 18 Q. What was the name of the 19 German affiliate? 20 A. German affiliate. 21 Q. It didn't have a particular 22 corporate name? 23 A. Not that I'm aware of. 24 Q. And it was also sent by Hans Page 197 1 Weber or H. G. Weber. 2 A. Yes. 3 Q. Correct? You know Hans Weber, 4 do you not? 5 A. Yes, I know him. 6 Q. What was his position with the 7 German affiliate at that time? 8 A. I don't recall what his 9 position was at that point in time. 10 Q. In June of 1984. 11 A. Right. 12 Q. What is his position with the 13 German affiliate now, Ms. Ashbrook? 14 A. I think he's the medical 15 director there. 16 Q. Is he a medical doctor? 17 A. I think so. 18 Q. The telex comes from Bad 19 Homburg, does it not? 20 A. Yes. 21 Q. Is Bad Homburg a location? 22 A. I think that's a city. 23 Q. The subject of Plaintiffs' 24 Exhibit No. 4 is a telex concerning Fluoxetine Page 198 1 and its registration in Germany, is it not? 2 A. Yes. 3 Q. What name was Fluoxetine being 4 marketed under in Germany? 5 A. I don't know. 6 Q. There was apparently some 7 meeting at the BGA on June 15th, 1984, was there 8 not? 9 A. That's what this telex 10 indicates. 11 Q. Were you present at the June 12 15th, 1984 meeting with the BGA? 13 A. No. 14 Q. The BGA is the German 15 equivalent of the Food and Drug Administration in 16 the United States, is it not? 17 A. That's how I understand it. 18 Q. Have you ever been present for 19 meetings with officials from the BGA? 20 A. No. 21 Q. Did you not ever go to Germany -- 22 A. No. 23 Q. -- in connection with 24 Fluoxetine? Page 199 1 A. No. 2 Q. Go to page ten -- I mean page 3 two of that document, item ten. Do you recall 4 reading that item ten stated comparative use of 5 concomitantly taken hypnotics and Benzodiazepines 6 in agitated retarded Fluoxetine patients versus 7 agitated retarded patients on comparitor. Reason -- 8 are you with me? 9 A. Yes, I'm with you. 10 Q. The BGA, which is an 11 equivalent to the United States FDA, right? 12 A. Yes. 13 Q. The BGA suspects Fluoxetine to 14 be a stimulating activating drug. Side effect 15 profile, suicides, suicide attempts. Do you see 16 that? 17 A. I see it. 18 Q. Turn to page three of that 19 document, item fourteen. That document mentions, 20 as we already explained by our telex to Doctor 21 Zerbe of June 8th, 1984, we need a careful 22 analysis of suicide and suicide attempts, patient 23 by patient symptomatology severity upon entry 24 into the study, and week-by-week until the event Page 200 1 occurred, dose of Fluoxetine side effects, et 2 cetera. Do you see that? 3 A. I see that. 4 Q. It says there also, this is a 5 very serious issue in the opinion of the BGA; 6 correct? 7 A. That's what it says. 8 Q. It also says it might well be 9 that we will have to recommend concomitant 10 tranquilizer intake for the first two or three 11 weeks in the package literature. Is that what it 12 says there under fourteen? 13 A. That's what it says. 14 Q. Do you recall these concerns 15 coming up in June of 1984 in connection with the 16 German government? 17 A. I recall that we had a series 18 of questions from the BGA. Since I have read it, 19 it's refreshed my mind. 20 Q. Let's talk about it then. 21 A. Okay. 22 Q. Apparently, as I read this, 23 your German affiliate, and the man who is now 24 your medical director in Germany, is having some Page 201 1 problems with the German affiliate to the Food 2 and Drug Administration, is that right? 3 A. Well, I don't know that I can -- 4 I'm not sure how the conversations took place and 5 who talked with the BGA. I can't make that 6 supposition. 7 Q. Well, the document there says 8 that they're having -- on page one, says they're 9 having discussions with the BGA, and gives a date 10 of June 15th, 1984, doesn't it? 11 A. But I do not know who 12 participated in that discussion. 13 Q. Well, it says our discussions, 14 does it not? 15 A. It does say that. 16 Q. And it's signed by J. Schenk 17 and H. G. Weber; correct? 18 A. That's what it is signed as. 19 Q. Is it reasonable to assume 20 that these were the gentlemen who were having 21 discussions with the BGA? 22 A. It could be. 23 Q. Is that a fair interpretation 24 of this language, this English language Page 202 1 transmission? 2 A. I guess. 3 Q. And there was a problem with 4 the BGA in getting Fluoxetine approved in 5 Germany, wasn't there? 6 A. They wanted responses to these 7 inquiries. 8 Q. And there was some problems 9 with respect to suicides in connection with the 10 approval, wasn't there? 11 A. It appears from this that was 12 one of their concerns. 13 Q. In fact, the last sentence of 14 that letter to you, Ms. Ashbrook, on page three 15 says it will be a difficult exercise for a final 16 successful outcome, doesn't it? 17 A. Yes. 18 Q. Had you just totally forgotten 19 about this issue when you told me that you had 20 not been involved with the issue of whether or 21 not Prozac and Fluoxetine causes suicide until 22 sometime after 1988? 23 MR. MYERS: I object to the form, I 24 don't know that that -- this memo are one and the Page 203 1 same. But answer it if you can. 2 A. We went through study by 3 study, and you're asking me what I recalled. I 4 didn't recall the details of what was in this. 5 Q. As I understand it, your 6 testimony this morning was that it wasn't until 7 after 1988 that you ever heard or heard mentioned 8 the issue of whether or not Prozac could cause 9 suicide. Was that what you said this morning? 10 A. Or this afternoon. 11 Q. That's what you said earlier. 12 A. Right, when you were asking 13 me. 14 Q. Now, in looking at this, it's 15 evident that that testimony was incorrect or at 16 least you had forgotten that you had been 17 involved with some problems in suicide with 18 respect to Fluoxetine; correct? 19 MR. MYERS: Same objection, answer it 20 if you can. 21 A. What was the question? 22 Q. In fact, you were dealing with 23 a problem with Prozac and suicide as early as 24 1984, weren't you? Page 204 1 A. These were the concerns and 2 requests for information that had come in. 3 Q. And it was a problem in 4 Germany, wasn't it? 5 MR. MYERS: I object to the form. 6 A. I don't know, I mean I can 7 read what's on this telex, that's all I have to 8 base an answer on. 9 Q. Does that not indicate to you 10 from reading that telex that at that time there 11 was a problem in Germany? 12 A. There was a concern, and they 13 wanted us to look into it. 14 Q. What did you do? 15 A. Well, this wasn't that I 16 personally did. There was a whole group of 17 people, and we did not understand what all this 18 meant, so we had a meeting, and again, a lot of 19 people were involved. 20 Q. All right. You remember now 21 that you had a meeting because you couldn't 22 understand this issue of Prozac and suicide? Are 23 we helping you now? 24 A. No. Page 205 1 MR. MYERS: Wait a minute, let me 2 object to the form. She said we didn't 3 understand all this. 4 A. The whole, all fifteen points. 5 Q. All right. Did you understand 6 point ten and point fourteen? 7 A. There needed to be discussion 8 for clarification with what they meant. 9 Q. Did you have a meeting on 10 point ten and point fourteen? 11 A. We had a meeting regarding 12 everything. 13 Q. Which would have included 14 point ten and point fourteen? 15 A. Yes. 16 Q. And what was it about point 17 ten that you didn't understand, Ms. Ashbrook? 18 A. Their interpretation and how 19 they wanted the data looked at. This is a 20 translation from German into English, and we 21 needed to really clarify and understand what did 22 they mean so we knew how we should respond or how 23 they wanted us to look at the data to be able to 24 respond to these questions. Page 206 1 Q. Have you ever spoken with Hans 2 Weber? 3 A. One-on-one? 4 Q. Yes. 5 A. On a few occasions. 6 Q. Were you speaking German or 7 English? 8 A. I speak in English. 9 Q. Was he speaking German or 10 English? 11 A. He speaks in English. 12 Q. Did you have any trouble 13 understanding his English when you spoke with 14 him? 15 A. Sometimes. 16 Q. What's the extent of his 17 educational background? 18 A. I don't know. 19 Q. And do you recall him slipping 20 into German and having some dialect that you 21 couldn't understand what he was saying? 22 A. No. 23 Q. This is in English, is it not, 24 this telex? Page 207 1 A. Yes. 2 Q. There's not anything about 3 what's written here that is unintelligible to 4 you, is there? 5 A. It's what does it mean, the 6 terms, we weren't necessarily familiar with. 7 Q. Well, let's look at ten then. 8 And I'll take it word by word, if you would like 9 me to, Ms. Ashbrook. Do you think there was a 10 translation problem with respect to any of the 11 words mentioned in ten, those words being 12 comparative use of concomitantly taken hypnotic 13 and Benzodiazepines in agitated retarded 14 Fluoxetine patients versus agitated retarded 15 patients on comparitors. Reason, the BGA 16 suspects Fluoxetine to be a stimulating 17 activating drug. Side effects profile, suicide 18 attempts. Do you think -- was there a concern at 19 the time that there had been some translation 20 problem with some of the words that were in item 21 ten? 22 A. What did they mean by 23 hypnotics, what drugs were they talking about 24 from a German standpoint. Agitated, retarded, Page 208 1 what did they mean by that. Again, their 2 interpretations may be different medically from 3 ours. They needed to have an open dialogue. 4 Q. But it wasn't a translation 5 problem, was it? 6 A. It was an understanding. I 7 didn't say -- 8 Q. But the difference in 9 understanding wasn't because Mister Weber spoke 10 German -- or Doctor Weber spoke German and you 11 spoken English? 12 A. No, no. 13 Q. In fact, Doctor Weber spent 14 two years here in the United States, didn't he? 15 A. Yes. 16 Q. And was stationed right here 17 at Eli Lilly in Indianapolis, wasn't he? 18 A. Yes. 19 Q. And you talked to him on 20 occasion while he was here that two-year period 21 of time. 22 A. Rarely. 23 Q. But on occasions? 24 A. I would say hi if I saw him in Page 209 1 the hall. 2 Q. And he would speak in English 3 on each occasion that you saw him? 4 A. Yes. 5 Q. You knew him, he knew you; 6 correct? 7 A. Yes. 8 Q. Go to fourteen. As we already 9 explained by our telex to Doctor Zerbe of June 10 8th, 1984, we need a careful analysis of suicides 11 and suicide attempts, patient by patient, 12 symptomatology severity upon entry into the 13 study, and week-by-week until the events 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. Now is there anything that I 20 read in item fourteen there that you suspect is a 21 translation problem? 22 MR. MYERS: Let me object to the form. 23 She never said there was a translation problem. 24 A. Uh-uh. It's an understanding. Page 210 1 Q. Is there something in fourteen 2 that you don't understand? 3 A. When you read it, yes. 4 Symptomatology, what are they talking about, what 5 did they mean? Severity upon entry into the 6 study, severity of what upon entry into the 7 study? Week-by-week until the event occurred, 8 what event, what are we talking about? I mean 9 when you've got to go in and look at data, you 10 need to specifically understand what they want. 11 And you read that, I couldn't tell, nor could 12 other people tell, that read it, what did they 13 want, what were they looking for. 14 Q. Did you call Doctor Weber or, 15 is it, Doctor Schenk? 16 A. I don't remember if she was a 17 physician or not. 18 Q. Did you call either Weber or 19 Schenk and ask them what they wanted? 20 A. I did not personally call 21 them. 22 Q. Who did? 23 A. I don't know who called them. 24 I know we ended up bringing them over here to sit Page 211 1 down and talk face to face about this. 2 Q. Were you present at that 3 meeting? 4 A. Yes. 5 Q. Then did you make notes at 6 that meeting? 7 A. At this point, I don't recall. 8 Q. Who was present at that 9 meeting? 10 A. I don't recall. 11 Q. Give me who you do recall. 12 A. I know Dave Hardison was 13 there, I was there, Doctor Weber was there, 14 Joanne Schenk was there. 15 Q. Where is Joanne Schenk now, do 16 you have any idea? 17 A. I have no idea. 18 Q. I'm sorry, I interrupted you, 19 go ahead. 20 A. There were probably systems 21 analysts there. I don't know which ones at that 22 point in time. 23 Q. Was Hans Weber there? 24 A. I already indicated yes. Page 212 1 Q. When was this meeting? 2 A. Sometime after this telex. 3 Q. How long after the telex? 4 A. I don't remember. 5 Q. A week? 6 A. I don't remember. 7 Q. A month? 8 A. I don't remember. 9 Q. This is in June of 1984. 10 Would it have been in the calendar year 1984? 11 A. I truthfully don't recall, I 12 would think it would have been. 13 Q. Did you go over these 14 problems? 15 A. That was the reason for the 16 meeting, to have a better understanding so we 17 knew how we needed to look at data to be able to 18 respond to their concerns. 19 Q. Did you take notes at that 20 meeting? 21 MR. MYERS: You already asked her 22 that. 23 MR. SMITH: I've forgotten. 24 A. I said I don't know if I did Page 213 1 or not. 2 Q. Would it have been your 3 practice to take notes at a meeting of that 4 nature? 5 A. I may or may not have, 6 depending on who all was there. 7 Q. Would somebody have been 8 assigned to take notes? 9 A. For the meeting? 10 Q. Yes. 11 A. Not generally. 12 Q. Have you seen any notes 13 concerning that meeting at any time? 14 A. I don't remember. 15 Q. If you had made notes, and I 16 think you said you're not sure whether or not you 17 made notes, what would you have done with those 18 notes? 19 A. Probably utilized them to see 20 if we could understand what they wanted so when 21 we started to get the different cuts of data, was 22 this hitting what they wanted. 23 Q. All right. Then what would 24 you have done with the notes after? Page 214 1 A. I don't know. 2 Q. Did you maintain the files? 3 A. I had some files, yes. 4 Q. Where would you have filed a 5 document such as this? 6 MR. MYERS: This what, notes? 7 Q. These notes. 8 A. My own personal notes. 9 Q. And then did you turn over 10 your personal notes on Fluoxetine to some member 11 of the legal department when that request came 12 down from the legal department that you all copy 13 and turn over your documents to the legal 14 department? 15 A. I had left the Fluoxetine 16 group before that request went out, and I had 17 left my files with the Fluoxetine group. 18 Q. So you assumed that whoever 19 became the custodian of your files would have 20 complied with that? 21 A. And several different people 22 did. 23 Q. Who did? 24 A. Some of them went to Doctor Page 215 1 Wernicke, some of them went to Laura Fludzinski. 2 Those were the two main recipients. 3 Q. Two what? 4 A. Two main recipients of my 5 files. 6 Q. Wernicke and Fludzinski? 7 A. Fludzinski, Dan Masica. 8 Q. And would your personal notes, 9 in connection with Prozac, concerning -- that 10 might have these notes, would they have been 11 turned over to one of these individuals? 12 A. If they had been kept. 13 Q. Let's go back to item ten. 14 Comparative use of concomitantly taken hypnotic 15 in Benzodiazepines in agitated retarded 16 Fluoxetine patients versus agitated retarded 17 patients on comparitors, reason, the BGA suspects 18 Fluoxetine to be a stimulating activating drug. 19 Side effect profile, suicides, suicide attempts. 20 What did you do about clarifying that request? 21 A. I don't recall detail. 22 Q. Do you recall anything done in 23 connection with item ten? 24 MR. MYERS: Other than what she Page 216 1 already told you? 2 MR. SMITH: She just said she didn't 3 recall anything. 4 MR. MYERS: She told you about five 5 minutes ago what the questions were about some of 6 the terms in there, so. 7 MR. SMITH: Those were on fourteen, 8 not on ten. 9 MR. MYERS: Uh-uh, you started on ten. 10 Q. Tell me what you recall doing 11 about the questions raised in ten? 12 A. What we would have asked would 13 have been what are you talking about hypnotics, 14 what kinds of drugs are you referring to. 15 Q. All right. Did he tell you? 16 A. I don't remember. 17 Q. Do you even remember that you 18 discussed what type of hypnotics he was talking 19 about? 20 A. I know we responded to all of 21 these issues, so we got information down to their 22 satisfaction so we both understood what the 23 request meant. And then, as an organization, we 24 responded to these. At this point, I do not Page 217 1 remember individual points within this. 2 Q. Well, we're up to June 26th, 3 1984, the date of this telex. Had there been any 4 studies done by Lilly on the comparative use of a 5 concomitantly taken hypnotics and Benzodiazepines 6 in agitated retarded Fluoxetine patients versus 7 agitated retarded patients on comparitors? 8 A. A study designed to do that? 9 Q. Yes. 10 A. No. 11 Q. Did you, after June 24th, do 12 any studies to investigate the comparative use of 13 concomitantly taken hypnotics and Benzodiazepines 14 in agitated retarded Fluoxetine patients versus 15 agitated retarded patients on comparitors? 16 A. Did we design a study to do 17 that? 18 Q. Yes. 19 A. Not that I recall. 20 Q. Before June 24th, 1984 -- June 21 26th, 1984, had Eli Lilly and Company ever done 22 any studies comparing agitated retarded 23 Fluoxetine patients versus agitated retarded 24 patients on comparitors? Page 218 1 A. We studied major depressive 2 disorder. 3 Q. That's not my question. To 4 your knowledge, before -- 5 A. With that objective, no. 6 MR. MYERS: Let him finish. 7 Q. Before June 26th, 1984, did 8 Eli Lilly and Company do any studies comparing 9 agitated retarded Fluoxetine patients versus 10 agitated retarded patients on comparitors? 11 A. A study designed to study 12 that, no. 13 Q. Since June 24th -- June 26th, 14 1984, has Eli Lilly and Company, to your 15 knowledge, done any studies comparing agitated 16 retarded Fluoxetine patients versus agitated 17 retarded patients on comparitor drugs? 18 A. Not to my knowledge. 19 Q. Before June 26th, 1984, had 20 Eli Lilly and Company ever done a study designed 21 to determine whether or not Fluoxetine was a 22 stimulating activating drug? 23 A. A study designed with those 24 objectives? Page 219 1 Q. Yes. 2 A. No. 3 Q. Since June 24th, 1994 -- June 4 26th, 1984, has Eli Lilly and Company done any 5 studies to determine whether or not Fluoxetine is 6 a stimulating activating drug? 7 A. Not to my knowledge. 8 Q. Before June 24th, 1984 -- June 9 26th, 1984, had Eli Lilly and Company ever done a 10 careful analysis of suicides and suicide 11 attempts, patient by patient symptomatology and 12 severity upon entry into the study in connection 13 with patients taking Fluoxetine? 14 A. Again, a study designed with 15 those specific objectives? 16 Q. Yes. 17 A. No. 18 Q. Since June 26th, 1984, has Eli 19 Lilly and Company done a study that had a careful 20 analysis of suicide and suicide attempts, patient 21 by patient, symptomatology severity upon entry to 22 a study with a week-by-week analysis until the 23 event occurred? 24 A. Not to my knowledge. Page 220 1 Q. Before June 26th, 1984, had 2 Eli Lilly and Company ever, in connection with 3 suicides, examined or done a study to examine the 4 dosage of Fluoxetine with respect to whether or 5 not it could or could not cause suicide or 6 suicide attempts? 7 A. Not to my knowledge. 8 Q. Since June 26th, 1984, has Eli 9 Lilly and Company ever done a careful analysis 10 concerning the dosage of Fluoxetine with respect 11 to whether or not the dosage of Fluoxetine would 12 cause suicide or suicide attempts? 13 A. Would you repeat, did we do an 14 analysis, was that the question? 15 (THE COURT REPORTER READ BACK THE 16 REQUESTED TESTIMONY.) 17 A. Have we done an analysis. I 18 know we responded to this question somehow, I 19 don't recall how. So we did an analysis at this 20 point, and I know some things have been done of 21 which I have no knowledge since I departed from 22 the group. 23 Q. Has Lilly ever done a clinical 24 study, clinical trial study, in connection with Page 221 1 that question? 2 A. Designed to do that? 3 Q. Yes. 4 A. To my knowledge, no. 5 Q. So, what was done as a result 6 of this meeting to answer the questions presented 7 by this telex? 8 A. We got an understanding. 9 Q. Beg your pardon? 10 A. We got an understanding of 11 what they were after, we looked at our entire 12 data base of what we had already collected from 13 our clinical trials on major depressive disorder 14 to answer these questions as best we could. 15 Q. And was that submitted to your 16 German affiliate? 17 A. The responses, when they were 18 all completed, were submitted to our German 19 affiliate. 20 Q. Did your German affiliate 21 submit that to the BGA? 22 A. They submitted responses to 23 the BGA, I don't know if they translated them to 24 German before they submitted them, so I don't Page 222 1 know if they took what we sent them and submitted 2 it. 3 Q. Whether they translated it or 4 not, it was your impression that you were 5 answering the questions so the answers could be 6 submitted to the BGA? 7 A. Yes. 8 Q. And do you know whether or not 9 the BGA approved Fluoxetine? 10 A. I think it's on the market 11 there. 12 Q. Do you know when they approved 13 Fluoxetine? 14 A. No, I don't remember. 15 Q. The June 26th, 1984 telex 16 indicates that the questions presented concerning 17 the analysis of suicide and suicide attempts on 18 page three is a very serious issue in the opinion 19 of the BGA, which is an equivalent to the FDA, 20 right? 21 A. That's correct. 22 Q. Then Doctor Weber theorizes 23 that it may well be that we will have to 24 recommend concomitant tranquilizer intake for the Page 223 1 first two or three weeks in the package 2 literature; correct? 3 A. That's what this says. 4 Q. In Germany. 5 A. Yes. 6 Q. In fact, Ms. Ashbrook, that's 7 exactly what occurred, isn't it? 8 A. I don't know. 9 Q. You don't know that the -- 10 A. What the package literature in 11 Germany says. 12 Q. You do not know that the 13 prescribing information for physicians in Germany 14 does in fact say that concomitant uses of 15 tranquilizers for the first two or three weeks 16 would be necessary? 17 A. No, I did not know that. 18 Q. Do you know anything about 19 what that language is in the German package 20 insert or prescribing information? 21 A. No, I do not. 22 (A SHORT RECESS WAS TAKEN.) 23 Q. Did you ever have discussions 24 or communications with any individuals at the Page 224 1 Food and Drug Administration, Ms. Ashbrook? 2 A. Did I have any? 3 Q. Yes. 4 A. Personal communications? 5 Q. Yes. 6 A. No. 7 Q. Did you ever go to the Food 8 and Drug Administration in Washington, D.C. and 9 discuss Fluoxetine with any member of the Food 10 and Drug Administration? 11 A. I have been in attendance in 12 meetings with the FDA. 13 Q. All right. In connection with 14 Fluoxetine? 15 A. I'm sorry, what did you say? 16 Q. In connection with Fluoxetine, 17 Prozac? 18 A. Yes. 19 Q. When did you first go to the 20 FDA? 21 A. I think the first time was to 22 the advisory committee meeting. 23 Q. That was in September, 1991? 24 A. No, no, this was the advisory Page 225 1 committee meeting when we were discussing the 2 potential for approval for major depressive 3 disorder. So that was sometime in the '80s, when 4 I was still with the project. 5 Q. All right. Was it after 6 submission of the NDA? 7 A. Yes. 8 Q. Which was September 23rd, 9 September of '83. 10 A. Yes. 11 Q. But before approval in 12 February -- I'm sorry, in December, 1987; 13 correct? 14 A. That's correct. 15 Q. Was it closer to September, 16 '83 or December, '87? 17 A. I think it was about smack in 18 the middle. 19 Q. Who went with you from Lilly 20 to Washington? 21 A. Doctor Zerbe, Doctor Thompson, 22 Joe Wernicke, Walt Offen. 23 Q. Who? 24 A. Walt Offen. Page 226 1 Q. Spell that last name? 2 A. O-F-F-E-N. 3 Q. Who is he? 4 A. Statistician. Lou Lemberger. 5 Those are the ones I can definitely remember. 6 Max -- I'm sorry, Max Talbott. 7 Q. Couldn't go to Washington 8 without Max, could you? 9 A. I don't think so. 10 Q. This meeting was in 1985, 11 wasn't it? 12 A. I don't know, I mean it was 13 sometime in the Fall of one of those years 14 between '83 and '87, so. 15 Q. Who from the Food and Drug 16 Administration was present? 17 A. This was the advisory 18 committee review. 19 Q. Well there were members of the 20 Food and Drug Administration -- 21 A. Doctor Leber was there. 22 Q. Was Leber on the advisory 23 committee? 24 A. I don't know how that works. Page 227 1 I don't think so. 2 Q. All right. Who else was there 3 from the FDA? 4 A. I've forgotten the name of the 5 medical reviewing officer. 6 Q. Tom Laughren? 7 A. Yes. Kapit, K-A-P-O-T? 8 Q. K-A-P-P-I -- or is it one P? 9 A. One. 10 Q. K-A-P-I-T. 11 Q. Was Doctor Temple there? 12 A. I don't remember. 13 Q. Anybody else that you can 14 remember besides Leber, Laughren and Kapit at the 15 meeting concerning -- with the advisory 16 committee? 17 A. You mean in -- what do you 18 mean? 19 Q. In Washington, what other 20 members of the FDA were there? 21 A. Those are the only ones I 22 recall. 23 Q. Were there any independent 24 members of the advisory committee there? Page 228 1 A. Yes, the advisory committee 2 was there. 3 Q. Who do you recall? 4 A. I don't know any of their 5 names. 6 Q. Approximately how many 7 individuals would that have been? 8 A. You know, it was more than 9 five, probably less than twelve. 10 Q. There was the formal meeting? 11 A. Yes. 12 Q. And where was that held? 13 A. At the FDA. 14 Q. In a meeting room? 15 A. Yes, wherever they hold those 16 down there. We went to a room. 17 Q. Room bigger than this, wasn't 18 it? 19 A. Yes. 20 Q. Were you present at the 21 meeting with the FDA officials before the actual 22 advisory committee meeting? 23 A. No. 24 Q. No? Page 229 1 A. (Witness moves head from side 2 to side.). 3 Q. Who was present from Lilly at 4 that meeting? 5 A. I know for sure Max was there. 6 Q. Who else? 7 A. I mean you want me to remember 8 this for a fact, I don't know. 9 Q. Is your best recollection for 10 a fact? 11 A. Best recollection would 12 probably be Doctor Zerbe and Doctor Wernicke. 13 Q. Was Leigh Thompson there? 14 A. (No response.). 15 Q. He was at the advisory 16 committee meeting, wasn't he? 17 A. Yes. 18 Q. Was he at the meeting before 19 that? 20 A. I don't know if he went to 21 that or not. 22 Q. Why didn't you go to this 23 meeting? 24 A. We take the minimum number of Page 230 1 people that need to go down there to conduct the 2 business. 3 Q. Yes, but you were already 4 there, weren't you? 5 MR. MYERS: Are these meetings at the 6 same time? 7 A. I don't know what you're 8 talking about. 9 Q. I'm talking about the meeting 10 that Lilly people had with the FDA before the 11 advisory committee meeting. 12 A. That wasn't at the same time. 13 Q. When was that? 14 A. Sometime prior to. 15 Q. A week or so? 16 A. Probably more like six weeks 17 to two months ahead of time. 18 Q. What is your understanding of 19 who from the Food and Drug Administration was 20 there at that initial meeting before the advisory 21 committee meeting? 22 A. (Witness gives no response.). 23 Q. I guess Leber was there? 24 A. Leber. Page 231 1 Q. Kapit was there? 2 A. (Witness gives no response.). 3 Q. Right? 4 MR. MYERS: If you know, tell him. 5 Q. Don't let me put words in your 6 mouth. 7 A. I don't know who was there. 8 Q. You're pretty sure Leber was 9 there, and you think that maybe Kapit was there; 10 correct? 11 A. What I would suspect is that 12 if you're at that point, you would have the 13 medical reviewing officer, and Kapit, and Leber, 14 at least. 15 Q. Now, since we've refreshed 16 your recollection on the suicide issue, do you 17 now remember that the issue of suicide and 18 Fluoxetine was discussed at this FDA meeting with 19 Lilly employees and FDA employees a short time 20 prior to the FDA meeting, advisory committee 21 meeting? 22 A. I don't know what was 23 discussed. 24 Q. I understand that. But they Page 232 1 came back and reported the suicide question as 2 being the issue, didn't they? 3 A. From the FDA? 4 Q. Yes. 5 A. I'm sorry, but I do not 6 remember that specifically. 7 Q. There were a number of topics 8 that had to be addressed between the meeting with 9 Lilly and the FDA, and before the advisory 10 committee meeting, weren't there? 11 A. What did you say? 12 (THE COURT REPORTER READ BACK THE 13 REQUESTED TESTIMONY.) 14 A. I mean as I recall from the 15 advisory committee meeting, we did a review of 16 the safety, we did a review of the efficacy, and 17 had a discussion on, you know, how much time 18 would we have to present, how much time would the 19 FDA present. I don't recall issues coming out, I 20 mean there was a lot of data on how they, you 21 know, what they wanted, but there isn't any one 22 thing that sticks out in my mind that they said 23 this is a major issue. 24 Q. Well, you wouldn't disagree if Page 233 1 there was other testimony that indicated that 2 between that period of time that there was a 3 concern about the data in connection with the 4 suicide issue, would you? 5 A. With respect to the FDA? 6 Q. Yes. 7 A. Again, it does not stand out 8 in my mind that that was an overriding issue. 9 Q. I understand that, but you 10 wouldn't disagree that it was an issue? 11 A. (Witness gives no response.). 12 Q. However you characterize it as 13 being overriding or not so overriding, it was an 14 issue that had to be addressed between those two 15 meetings before the advisory committee meeting, 16 wasn't it? 17 A. I don't recall. 18 Q. The meeting with the FDA 19 advisory committee was, you think, sometime in 20 '84; correct -- I mean '85? 21 A. I said I don't know. 22 Q. It was before this meeting 23 that you all had in connection with the BGA, I 24 mean it was after the BGA issue on suicide came Page 234 1 up, wasn't it? 2 A. Again, at this point, the 3 chronology in there is fuzzy in my mind. I think 4 it was. 5 Q. The FDA meeting was after the 6 BGA issue had come up? 7 A. Yes. 8 Q. Does that help you that there 9 was an issue of suicide on the agenda at the 10 advisory meeting with the FDA? 11 A. I don't recall. 12 Q. You, as a project leader at 13 the time, knew at the time of the advisory 14 meeting that the German government was concerned 15 about the suicidality issue, didn't you? 16 A. Yes. 17 Q. And you had done some work in 18 connection with reanalyzing it or recalculating 19 data to answer questions to send back to your 20 German affiliate, hadn't you? 21 A. I personally didn't reanalyze 22 or recalculate. 23 Q. You had it done. 24 A. Yes. Along with other people. Page 235 1 I didn't solely direct this. 2 Q. All right. But you know it 3 was done. 4 A. Yes, we know we responded to 5 the BGA. 6 Q. You know these issues were 7 addressed, issues ten and fourteen. 8 A. Yes. 9 Q. Weren't they? 10 A. (Witness moves head up and 11 down.). 12 Q. This concern of the German 13 government, and what you all had done in 14 answering the questions presented by the German 15 government, was not passed on to the Food and 16 Drug Administration, was it, Ms. Ashbrook? 17 A. Would you repeat your 18 question? 19 MR. SMITH: Read it back. 20 (THE COURT REPORTER READ BACK THE 21 REQUESTED TESTIMONY.) 22 A. I think that it was submitted, 23 it would have been submitted in annual report. 24 Q. But it wasn't submitted in the Page 236 1 advisory committee meeting, was it? 2 A. I don't understand what -- in 3 their big presentation? 4 Q. Yes. 5 A. Did we go over point by point? 6 Q. Was the Food and Drug 7 Administration made aware that the BGA, the 8 German cousin to the United States Food and Drug 9 Administration, had serious concern about the 10 suicidal nature of Fluoxetine? 11 MR. MYERS: At any time or before the 12 meeting? 13 Q. At any time up until the 14 meeting, and including the meeting of the 15 advisory committee in approximately 1985. 16 A. Again, it had been prepared. 17 I was never one-on-one communication with the 18 FDA, there were others that were. I can't say. 19 Q. Well, in fact the Food and 20 Drug Administration was never made aware of it, 21 were they, Ms. Ashbrook? 22 MR. MYERS: When you say never, you 23 mean at any time, because she's already said she 24 thought it was in an annual report. Page 237 1 Q. Up until -- they were never 2 made aware of it up until after the advisory 3 meeting in September -- or in 1985? 4 A. I can't answer that question. 5 Q. Do you know if anybody -- were 6 you present at the advisory meeting -- you were. 7 A. I was in the audience at the 8 advisory committee presentation. 9 Q. Right, you were there at the 10 presentation, at the advisory committee? 11 A. Yes. 12 Q. And did you hear anybody there 13 advise the Food and Drug Administration or the 14 advisory committee in 1985 that the British -- 15 that the BGA, the German equivalent to the Food 16 and Drug Administration, was concerned that 17 comparative use of concomitantly taking hypnotics 18 and Benzodiazepines in agitated retarded 19 Fluoxetine patients versus agitated retarded 20 patients on comparitors, that the reason for this 21 concern was a suspicion that Fluoxetine might be 22 a stimulating activating drug with a side effect 23 profile of suicide and suicide attempts? 24 A. I was not privy to what kind Page 238 1 of conversations went on between Lilly and the 2 FDA prior to that meeting. 3 Q. But you were privy to the 4 presentation that Lilly made at the meeting, 5 weren't you? 6 A. I was there, yes. 7 Q. And nothing was ever said 8 about that at that presentation, was there? 9 MR. MYERS: He wants to know if what 10 he read to you was part of the presentation. 11 A. I don't recall. 12 Q. Well, do you not recall 13 because you haven't -- because you've forgotten? 14 A. I know we did a review, an 15 overall review of efficacy and an overall review 16 of safety. 17 Q. That's not what I asked you. 18 MR. MYERS: She's explaining her 19 recollection, Paul. 20 Q. Did anybody from Lilly advise 21 the Food and Drug Administration advisory 22 committee in 1985 that the BGA, the German 23 equivalent to the Food and Drug Administration, 24 that they had serious concerns about Fluoxetine Page 239 1 and the suicidal effects of Fluoxetine? 2 MR. MYERS: It's been asked and 3 answered. Answer it one more time, and one more 4 time only. Tell him what you recall. 5 A. I don't recall. 6 Q. Do you think that would have 7 been something that you would have recalled had 8 it been presented in that fashion? 9 A. Again, what I recall was there 10 was an overview of safety, and there was an 11 overview of efficacy, and we talked about the 12 concerns. I don't recall what the slide said. 13 Q. What what said? 14 A. What the slide said. 15 Q. Well, there was an oral 16 presentation made by Lilly, wasn't there? 17 A. Yes. 18 Q. Who made it? 19 A. Several people. 20 Q. Who? 21 A. Boy. Leigh Thompson may have 22 introduced it, Bob Zerbe, Joe Wernicke. I don't 23 remember if Lou talked or not, Lou Lemberger. 24 Q. Do you remember any of those Page 240 1 individuals mentioning the BGA, the German 2 equivalent to the FDA? 3 A. I don't recall. 4 Q. Do you recall any of those 5 individuals mentioning the country Germany? 6 A. I don't recall. 7 Q. Do you recall any of those 8 individuals mentioning to the advisory committee 9 that the report was that the BGA might be 10 requiring at least a package insert that required 11 a use of tranquilizers in connection with 12 Fluoxetine for a period of time? 13 A. At the advisory committee 14 formal presentation? 15 Q. Yes. 16 A. I don't recall. 17 Q. Did you have anything to do 18 with preparing the written presentation? 19 A. No. 20 Q. Did you read the written 21 presentation? 22 A. I may have seen it in a dress 23 rehearsal, I don't think I read it. 24 Q. You all had a dress rehearsal Page 241 1 before your presentation to the advisory 2 committee meeting? 3 A. (Witness moves head up and 4 down.). 5 Q. How did everybody dress? 6 A. Very dressed up. 7 Q. Those rehearsals are always 8 better when everyone is dressed. 9 Q. The German government was 10 never mentioned in the dress rehearsal or in the 11 oral presentation that you recall, was it? 12 A. That's correct. 13 MR. SMITH: Are you going to plug on 14 or do you want to break? 15 MR. MYERS: I think that since we have 16 another day scheduled, that I think that 5:30 17 would be pushing the limits of reasonableness. 18 MR. SMITH: Is it 5:30? 19 MR. MYERS: What I'm saying is if you 20 want to go to 5:30 and quit, I think that would 21 be a reasonable time to stop since we have a 22 whole other day scheduled. Unless you all want 23 to stop here. But I don't think that from a 24 fatigue, mentally and physically -- Page 242 1 MR. SMITH: Oh, she looks likes she's 2 getting pretty worn, so no further questions. 3 MR. MYERS: No questions. 4 * * * * * * * * * * 5 (THE DEPOSITION WAS RECESSED 6 UNTIL THE FOLLOWING DAY, AT 7 WHICH TIME THE PROCEEDINGS 8 CONTINUED AS FOLLOWS:) 9 * * * * * * * * * * 10 CONTINUED DIRECT EXAMINATION 11 BY MR. SMITH: 12 Q. Ms. Ashbrook, are you ready to 13 continue? 14 A. Yes. 15 Q. Before we continue, I want to 16 give you the opportunity this morning, and you'll 17 have another opportunity to review your 18 deposition once you receive it in written form. 19 But is there anything that maybe has come to mind 20 over the evening that would cause you to want to 21 change, amend or in any way alter any of the 22 testimony you gave yesterday? 23 A. No. 24 Q. Has there been some question Page 243 1 come to mind concerning the potential that you 2 might have misunderstood some of my questions 3 yesterday, has that occurred to you? 4 A. I don't think so. 5 Q. Again, you'll have the 6 opportunity to review the deposition once it's 7 written and make any changes that need to be 8 made. All right? 9 A. Okay. 10 Q. When we last talked, I believe 11 that we were discussing the advisory committee 12 meeting in 1985. 13 MR. MYERS: Or thereabouts. 14 Q. Or thereabouts. Do you have 15 any recollection today of any clear time -- 16 A. No, I don't. 17 Q. -- with respect to when that 18 occurred? 19 A. No, I don't. 20 Q. As I understand it, some 21 corporate representatives from Lilly flew to 22 Washington and met with representatives of the 23 Food and Drug Administration a short time prior 24 to the actual advisory committee meeting; is that Page 244 1 correct? 2 A. I think that occurred. 3 Q. Then there was a dress 4 rehearsal at Lilly a few days before the meeting 5 itself in connection with this advisory committee 6 meeting that you all were going to attend, is 7 that right? 8 A. Yes. 9 Q. And at that time, there were 10 discussions that everybody practiced their area 11 of their presentation to the advisory committee 12 meeting, is that right? 13 A. Yes. 14 Q. Do you recall during that 15 dress rehearsal meeting whether or not potential 16 questions were posed to the group or members of 17 the group who were going to give their 18 presentations to practice responding to any 19 potential areas of inquiry that the advisory 20 committee might make? 21 A. Not at the dress rehearsal. 22 Q. Were there some earlier than 23 that or on some other occasion? 24 A. Where? Page 245 1 Q. Where there was a review of 2 potential issues that could come up at the 3 advisory committee meeting where you would 4 discuss what would be the most appropriate way to 5 answer potential questions that might be raised 6 by members of the advisory committee meeting? 7 A. We knew what the FDA wanted us 8 to cover in the meeting, that's what the 9 presentation was about. 10 Q. All right. 11 A. There were -- if people asked 12 questions, what might they be. 13 Q. Yes. 14 A. That was discussed. 15 Q. All right. Do you remember 16 what the general areas of potential questions 17 were discussed? 18 A. Broad categories of efficacy 19 and safety. 20 Q. With respect to safety, was 21 there discussions concerning the potential for 22 suicide and Fluoxetine? 23 A. Not that I recall. 24 Q. Was there any discussion in Page 246 1 the dress rehearsal of the potential for suicide 2 and Fluoxetine? 3 A. In the actual presentation? 4 Q. No, in the dress rehearsal 5 where you were discussing potential questions 6 that might be raised by the advisory committee 7 meeting. 8 A. The dress rehearsal was 9 strictly a practice of the presentations because 10 the FDA had given us, you know, a set time to 11 make our presentation. So it was the formal 12 presentation that was practiced to make sure that 13 we would be within the time, and that what we 14 said was understood. 15 Q. But you knew that the advisory 16 committee would have an opportunity, and in fact 17 probably would direct questions to Lilly 18 personnel in connection with the Fluoxetine 19 application. 20 A. Did you say did I know that 21 they would? 22 Q. Yes. 23 A. That was a possibility. I 24 don't know that I personally knew that they Page 247 1 would, I had never been to a meeting before, I 2 didn't know what to expect. 3 Q. Well, one of the purposes of 4 that meeting in 1985, or approximately, was to 5 give the advisory committee the opportunity to 6 question Lilly employees concerning particular 7 details of the Fluoxetine application; correct? 8 A. The advisory committee 9 meeting, as I understood it, was the opportunity 10 for a formal presentation from Lilly and a formal 11 presentation from the FDA about Fluoxetine. 12 Q. All right. Normally wasn't it 13 your understanding that members of the advisory 14 committee could ask questions to either Lilly 15 personnel or the Food and Drug Administration 16 officers that were present at the meeting? 17 A. I don't know that I knew that. 18 Q. Well, let me ask you this: 19 Did in fact members of the advisory committee 20 pose questions to either Lilly employees or 21 members of the FDA at that meeting? 22 A. I don't remember. 23 Q. What were the potential areas 24 of questioning that Lilly employees were Page 248 1 foreseeing could potentially come up? 2 A. I don't recall other than 3 there were broad categories of safety and 4 efficacy. 5 Q. Do you recall whether or not 6 in that category of safety there were discussions 7 of the potential of Fluoxetine for suicidality? 8 A. I do not recall. 9 Q. Do you recall if there were in 10 fact questions raised at the advisory committee 11 meeting in 1985 concerning the potential of 12 Fluoxetine for suicidality? 13 A. I do not recall. 14 Q. Do you recall whether or not 15 in either the oral presentation or the written 16 materials that were submitted to the advisory 17 committee the issue of suicidality and Fluoxetine 18 was ever addressed? 19 A. I do not recall. 20 Q. Did the meeting occur in 21 Washington, D.C. or Hartford, Maryland? 22 A. Wherever the FDA is. 23 Q. Outside of? 24 A. Rockville. Page 249 1 Q. Rockville, Rockford. 2 MR. MYERS: Something like that. 3 Q. Somewhere in Maryland, a 4 stone's throw from the Washington, D.C. area 5 proper; correct? 6 A. Yes. 7 Q. And you were at that meeting? 8 A. Yes. 9 Q. Why were you asked to attend 10 that meeting? 11 A. Why was I asked to attend the 12 meeting? 13 Q. Yes. 14 A. I was a department head at 15 that time of the group. I went along, you know, 16 to see what went on at one of these meetings, I 17 had not been to one before. 18 Q. Did you participate in the 19 meeting at all? 20 A. No. 21 Q. You didn't make any 22 presentations? 23 A. No. 24 Q. How long did the meeting last? Page 250 1 A. No more than a day. 2 Q. Do you remember how long you 3 were in the Washington area? 4 A. We were there for the meeting, 5 I mean we went in and then went back out. 6 Q. Did you fly commercial or did 7 you fly on Air Lilly? 8 A. We flew on the Lilly plane. 9 Q. After you returned to 10 Indianapolis, was there any work to be done in 11 connection with the Fluoxetine application in 12 response to any specific questions that had been 13 raised by members of the advisory committee? 14 A. Not that I recall. 15 Q. Do you remember whether or not 16 the advisory committee had any questions or had 17 any input in that meeting? 18 A. What do you mean by had any 19 input? 20 Q. Whether there was a dialogue 21 during the meeting with members of the advisory 22 committee. 23 A. There was a discussion between 24 the FDA and the advisory committee as to the Page 251 1 safety and efficacy of Fluoxetine based upon the 2 information that they had. 3 Q. What do you recall about that 4 discussion? 5 A. I really don't recall a lot of 6 that discussion. 7 Q. I understand that, but what do 8 you recall? 9 A. I don't recall -- I know a 10 discussion took place. 11 Q. Do you recall what the FDA 12 officials reported to the advisory committee 13 concerning what their impression was at that time 14 with respect to the safety of Fluoxetine? 15 A. I do not recall. 16 Q. Do you recall safety being any 17 particular concern at that meeting? 18 A. I don't recall. 19 Q. Did you ever participate in 20 any other meetings with the Food and Drug 21 Administration? 22 A. Yes. 23 Q. When was the next time? 24 A. November of '87. Page 252 1 Q. What was the purpose of that 2 meeting? 3 A. To discuss the final labeling 4 for Fluoxetine. 5 Q. Who was present from Lilly at 6 that meeting? 7 A. Max Talbott, Dan Masica, Joe 8 Wernicke, myself. 9 Q. Was Leigh Thompson there? 10 A. I don't remember. 11 Q. Was Doctor Zerbe there? 12 A. No. 13 Q. Was Doctor Beasley there? 14 A. No. 15 Q. Doctor Heiligenstein? 16 A. No. 17 Q. Doctor Kotsanos? 18 A. No. 19 Q. Doctor Lemberger? 20 A. I don't recall. 21 Q. You're pretty sure that it was 22 just the four of you? 23 A. That's my recollection. 24 Q. Who was present at this Page 253 1 meeting with the Food and Drug Administration? 2 MR. MYERS: For the Food and Drug 3 Administration, you mean? 4 MR. SMITH: Yes. 5 MR. MYERS: You said with. 6 A. Could you repeat that? 7 MR. MYERS: He wants to know who was 8 there from the FDA. 9 A. Leber, Kapit, and the medical 10 reviewing officer, was it Laughren? The medical 11 reviewing officer. 12 MR. MYERS: L-A-U-G-H-R-E-N. 13 Q. Was Doctor Temple there? 14 A. I don't recall. 15 Q. Who was the secretary or the 16 head of the Food and Drug Administration at that 17 time? 18 A. I don't recall. 19 Q. Where did the meeting occur? 20 A. In a conference room at the 21 FDA. 22 Q. Did you all fly up on the 23 Lilly corporate plane or did you fly 24 commercially? Page 254 1 A. Probably went on the Lilly 2 plane. 3 Q. How many planes did Lilly have 4 at that time? 5 A. I don't know. 6 Q. More than one? 7 A. I don't know. 8 Q. Well, you said one of the 9 Lilly planes, that indicates to me they had more 10 than one. 11 MR. MYERS: If you know, Earlene, tell 12 him. If you don't, tell him that. 13 A. I don't know how many planes 14 they had. 15 Q. Have you been on more than one 16 Lilly plane? 17 A. Yes. 18 Q. How many different Lilly 19 planes have you been on? 20 A. Two. 21 Q. And the purpose of this 22 meeting was to discuss the final labeling for 23 Fluoxetine? 24 A. Yes. Page 255 1 Q. This would be the package 2 insert? 3 A. That's correct. 4 Q. That accompanied each package 5 of Fluoxetine; correct, or Prozac? 6 A. It's package literature, yes. 7 Q. Were there discussions at that 8 meeting concerning what the package literature 9 should contain concerning whether or not Prozac 10 has any relationship to suicide? 11 A. No, not that I recall. 12 Q. There were no discussions that 13 you recall? 14 A. That's right. 15 Q. Do you recall any other 16 discussions concerning the suicide aspects of the 17 Prozac label? 18 A. Specifically with that, we 19 talked about the whole label, so all the 20 different sections, and they talked about what 21 would be in the different sections, and suicide 22 was a topic. 23 Q. All right. And what was said 24 concerning that? Page 256 1 A. Specifically, I don't recall. 2 It would be what was in the label. 3 Q. Do you remember there being 4 any discussion concerning whether or not the 5 label should have more information concerning 6 suicide and Prozac than was actually contained in 7 the product information? 8 MR. MYERS: Before she answers, let me 9 object to the form since the question assumes 10 that what was in there had to do with some 11 relationship between Prozac and suicide. 12 MR. SMITH: All right. 13 A. I'm sorry, what was the 14 question? 15 (THE COURT REPORTER READ BACK THE 16 REQUESTED TESTIMONY.) 17 MR. MYERS: Same objection. 18 A. I'll reiterate what I said 19 previously, that we talked about where you place 20 the information in the leaflet. That's what I 21 recall. 22 Q. Then would you -- 23 MR. SMITH: Ms. Reporter, read the 24 question again and see if she can answer the Page 257 1 question. 2 (THE COURT REPORTER READ BACK THE 3 REQUESTED TESTIMONY.) 4 MR. MYERS: Same objection. This is 5 the last time she's going to answer that 6 question. Go ahead and answer it, Earlene. 7 A. I don't recall that 8 conversation. 9 Q. All right. So is the answer 10 no, I don't recall? 11 A. No, I don't recall. 12 Q. Did anyone from Lilly at that 13 meeting advise members of the Food and Drug 14 Administration that at that time the German 15 equivalent to the FDA was requiring more 16 information concerning suicide and Fluoxetine 17 than was contained in the proposed label for U.S. 18 product of Prozac? 19 MR. MYERS: I object to the form, that 20 assumes facts that are not and will not be in 21 evidence. Go ahead and answer. 22 A. I do not recall any 23 conversation regarding that. 24 Q. So if it was brought to the Page 258 1 attention of those members of the Food and Drug 2 Administration at that time that the British 3 government was requiring different labeling 4 concerning suicide, you don't recall it? 5 MR. MYERS: Same objection as to the 6 form. Go ahead and answer. 7 A. There was no input from the 8 British government. 9 Q. Did I say British government? 10 I meant German government. Why would they call 11 themselves the BGA, I think they did that to 12 confuse me. Let me ask you my question again, 13 and try to get it in at least the right country. 14 If there was any mention made to the Food and 15 Drug Administration at that meeting that the 16 German government was requiring a different 17 package insert concerning suicide with respect to 18 Fluoxetine, you didn't hear anybody from Lilly 19 mentioning that to the Food and Drug 20 Administration in that November, 1987 meeting? 21 MR. MYERS: Same objection. 22 A. I do not recall any discussion 23 about that. 24 Q. Were there any changes made in Page 259 1 the label for Fluoxetine after that November '87 2 meeting and before the product was first put on 3 the market? 4 A. Changes were made at the FDA's 5 request. 6 Q. What changes were made? 7 A. They asked for treatment 8 emergent signs and symptoms, they asked for some 9 things to be moved around into the different 10 sections. 11 Q. Such as? 12 A. Such as what? 13 Q. What things were being moved, 14 do you recall anything that was moved from one 15 area of the package insert to the other? 16 A. Specifically, no, I don't 17 remember specifics, but there was discussions 18 around where to place things. 19 Q. Did you work on any of those 20 changes? 21 A. I saw that the changes were 22 carried out by people who could do that. 23 Q. Do you recall who did that at 24 your direction? Page 260 1 A. Systems analysts. 2 Q. Why would a systems analyst be 3 doing that? 4 A. When they asked for treatment 5 emergent signs and symptoms, we had not cut our 6 data base that way, we had to go back and rerun 7 the data base. They also asked us to have the 8 most up-to-date numbers at that point in time, so 9 it was an increase in patient population and a 10 different way of looking at adverse events. The 11 system was programmed to do that, so a systems 12 analyst had to do that task. 13 Q. When you talk about treatment 14 emergent signs and symptoms, in November of 1987, 15 Prozac wasn't being prescribed to the public in 16 general, was it? 17 A. No. 18 Q. And, so, any treatment 19 emergent signs and symptoms would only have been 20 those treatment emergent signs and symptoms that 21 would have occurred during the clinical trials. 22 A. That's correct. 23 Q. What is your best judgment 24 concerning the number of individuals that had Page 261 1 been treated with Fluoxetine in the clinical 2 trials in November of 1987? 3 A. Could you repeat that 4 question, I didn't -- I don't understand what I'm 5 supposed to answer. 6 Q. How many people had been 7 treated with Fluoxetine during the clinical 8 trials by November, 1987? 9 A. It was around fifty-six 10 hundred. 11 Q. And of those fifty-six hundred 12 individuals, is that fifty-six hundred 13 individuals that had actually received the drug 14 Fluoxetine or did that include individuals who 15 had been treated with placebo and comparitor 16 drugs? 17 A. The fifty-six hundred referred 18 to people that had received Fluoxetine. 19 Q. So there may have been more 20 patients enrolled in the clinical trials because 21 during the clinical trials you had to compare 22 patients with either a comparitor drug or with a 23 placebo; correct? 24 A. Correct. Page 262 1 Q. But in November of 1987, five 2 thousand six hundred people had actually received 3 the drug Fluoxetine. 4 A. At least one dose of the drug 5 Fluoxetine. 6 Q. Of those fifty-six hundred 7 people, how many individuals had received the 8 drug for a two-week period of time, regardless of 9 the dosage? 10 MR. MYERS: Two weeks or longer, not 11 just for two weeks? 12 MR. SMITH: Yes, that would probably 13 be a better way to do it, two weeks or longer. 14 A. I don't recall that. 15 Q. It would have been a smaller 16 number than fifty-six hundred, wouldn't it? 17 A. I don't understand your 18 question. 19 Q. During the clinical trials, 20 you would have patients who would begin treatment 21 on Fluoxetine, and then stop treatment on 22 Fluoxetine before the conclusion of the trial, 23 would you not? 24 A. Yes. Page 263 1 Q. Those would be what we 2 considered early discontinuations, early dropouts 3 or people just didn't show back up to participate 4 in the clinical trials; correct? 5 A. Yes. 6 Q. What I'm trying to get from 7 you is in November of 1987, immediately before 8 the drug was released for public consumption, as 9 prescribed by physicians, how many individuals of 10 those fifty-six hundred had been on the 11 medication for what periods? 12 A. I can't answer that question. 13 Q. There would be data reflecting 14 that, would there not? 15 A. Yes. 16 Q. In other words, you were 17 calculating the number of individuals enrolled in 18 the clinical trials; correct? 19 A. We knew the number that were 20 enrolled in the clinical trials. 21 Q. And you knew the number that 22 actually received one dose of Fluoxetine. 23 A. Yes. 24 Q. And you knew the number of Page 264 1 individuals who dropped out or were early 2 discontinued from the study. 3 A. Yes. 4 Q. And you knew what point in the 5 clinical trials those individuals had dropped 6 out, too, didn't you? 7 A. Yes. 8 Q. What was the longest period of 9 time that a clinical trial was going to last? 10 MR. MYERS: Let me object to the form 11 and ask when you say the trial was going to last, 12 do you mean how long would a patient be on the 13 drug? Because it could be rolling enrollment or 14 something like that, it could last a couple of 15 years. 16 Q. The various protocols set 17 forth, did they not, the proposed study duration 18 of the trial? 19 A. Yes. 20 Q. It might be they're going to 21 be exposed to Fluoxetine for two weeks, six 22 weeks, two months; correct? 23 A. Yes. 24 Q. What was the longest period of Page 265 1 time that a clinical trial was to expose patients 2 to Fluoxetine? 3 A. The double-blind portions of 4 the study, with treatment of the drug, were 5 generally six weeks. 6 Q. How about the comparitor 7 studies, what were they generally in time 8 duration? 9 A. The double-blind portion of 10 the studies was generally six weeks. 11 Q. All right. Can you give me 12 any percentage of these fifty-six hundred 13 individuals who had been treated with Fluoxetine 14 in November of 1987 that would have been exposed 15 to the drug for six weeks or less? 16 A. No, not off the top of my 17 head. 18 Q. Would it be more or less than 19 fifty percent of the people? 20 A. I can't answer that. 21 Q. Who would be able to answer 22 that? 23 A. I don't know that anybody, off 24 the top of their head, I mean it's in the data. Page 266 1 Q. Who would be able to find that 2 data easiest? 3 A. The regulatory department. 4 Q. What percentage of your trials 5 up to November, 1987 were double-blind trials? 6 A. The majority of them were 7 double-blind trials. 8 Q. So could we say the majority 9 of the fifty-six hundred number would have been 10 on Fluoxetine for probably not longer than six 11 weeks? 12 A. No. 13 Q. Why? 14 A. Protocols had the extensions. 15 Q. All right. What percentage of 16 the protocols had the extensions? 17 A. Again, the majority of them. 18 Q. The extension provided for 19 what with respect to how long the patient was to 20 continue on Fluoxetine? 21 A. I don't recall a time limit 22 set on the open-label extensions. 23 Q. Was there any? 24 A. I don't recall. Page 267 1 Q. In November of 1987, then, 2 approximately fifty-six hundred individuals had 3 been exposed to Fluoxetine? 4 A. Yes. 5 Q. And had received at least one 6 dose of Fluoxetine; correct? 7 A. That's correct. 8 Q. And that's as accurate as you 9 can give me, at least one dose, as far as whether 10 somebody was on two weeks, four weeks, six weeks 11 or indefinitely? 12 A. That's correct. 13 Q. Now, do you know today how 14 many people have received Fluoxetine? 15 A. I have no idea. 16 Q. You read in the press it's 17 somewhere around five million people. Does that 18 sound accurate to you? 19 A. I haven't read in the press 20 lately. 21 Q. You haven't written or read 22 the press? 23 A. I haven't read it lately, I 24 really don't know. Page 268 1 Q. Any other labeling changes 2 that you recall? 3 A. That was the major one that I 4 recall, was with the treatment emergent signs and 5 symptoms. 6 Q. Were you present at any other 7 meetings with individuals from the Food and Drug 8 Administration? 9 A. Yes. 10 Q. When was the next time? 11 A. Somewhere in 1988, before I 12 left my job as department head. So early 1988. 13 Q. That would have been right 14 before you left as the department head of medical 15 in charge of the Fluoxetine group? 16 A. Yes. 17 Q. And right before you started 18 as the department head of medical information 19 systems, is that right? 20 A. Yes, it was -- so that was 21 Fall, so it was somewhere probably in the first 22 quarter of 1988 I went back down to the FDA. 23 Q. What for? 24 A. To discuss future submissions. Page 269 1 Q. Future submissions of 2 Fluoxetine? 3 A. Yes. 4 Q. For other purposes? 5 A. Yes. 6 Q. Who was present at that 7 meeting from Lilly? 8 A. I recall Max Talbott, Dan 9 Masica. Those are the two that I specifically 10 recall. 11 Q. Was Leigh Thompson or Bob 12 Zerbe or Fuller or Wong or anyone else there? 13 A. Not that I recall. 14 Q. Who was the medical monitor on 15 Fluoxetine at the time? 16 A. Joe Wernicke. 17 Q. Was he there? 18 A. I said I don't recall if he 19 was or wasn't. 20 Q. Do you recall whether Beasley, 21 Heiligenstein, Kotsanos or any of those 22 individuals were there? 23 A. No, not at that time. 24 Q. Who was there from the FDA? Page 270 1 A. Leber. 2 Q. Anybody else, Kapit? 3 A. I don't recall that he was 4 there then. 5 Q. Temple? 6 A. I don't recall. 7 Q. Laughren? 8 A. I don't recall. 9 Q. Were there -- you say that the 10 subject of the discussion was future submissions 11 for Fluoxetine for other purposes, is that right? 12 A. Yes. 13 Q. Was safety discussed in that 14 meeting? 15 A. No. 16 Q. Then what specifically was the 17 subject of that meeting? 18 MR. MYERS: Before she answers, Paul, 19 I'll let her tell you generally what the 20 indications were, but she's not going to go into 21 any specifics about nonapproved indications since 22 she already said safety was not an issue. But 23 kind of generally tell him what the topics were, 24 if you can. Page 271 1 A. The topics were to discuss 2 submissions for bulimia and weight loss. 3 Q. Was this a procedural meeting 4 in what type of procedure they were asking that 5 you employ? 6 A. What do you mean by what type 7 of procedure we would employ? 8 Q. Were they having some problems 9 or were they wanting to change up the manner in 10 which you were transmitting case report forms or 11 transmitting data then? 12 A. No. 13 Q. Was the issue of the emergent 14 suicidal ideation, suicidal acts or overdoses or 15 anything in connection with the violent or 16 aggressive behavior in those patients discussed? 17 A. No. 18 Q. Did you fly on the company 19 plane to Washington for that meeting? 20 A. Probably. 21 Q. Were you asked for more data 22 in this first quarter 1988 meeting in connection 23 with the clinical trials that were ongoing with 24 respect to these other indications? Page 272 1 A. It was a discussion on what 2 kind of clinical trials needed to be done, and 3 for what kind of duration, and I think they 4 wanted a longer term study completed for those 5 indications. 6 Q. Bulimia and weight loss? 7 A. Yes. 8 Q. Were depressed individuals 9 included in those studies involving bulimia and 10 weight loss? 11 A. I don't recall what were the 12 inclusion and exclusion criteria for those 13 protocols. 14 Q. Was it recognized at that time 15 that along with bulimia and weight loss there was 16 a comorbidity of depression, depression in 17 association with those conditions? 18 MR. MYERS: I object to the form, I 19 think that's probably getting close to a medical 20 question. You can tell him if you know. 21 A. I can't respond to that. 22 Q. You don't recall seeing any 23 literature associating depression with those 24 conditions known as bulimia and obesity? Page 273 1 MR. MYERS: Same objection. 2 A. Not that I recall. 3 Q. How much longer a study were 4 they asking for? 5 MR. MYERS: Don't answer that, that's 6 proprietary and otherwise governed by the order 7 of both of these courts. 8 MR. SMITH: I just wanted to know the 9 number of weeks. Number of weeks is proprietary? 10 MR. MYERS: It is. 11 MS. ZETTLER: Paul, what studies are 12 you talking about? 13 MR. SMITH: The bulimia and weight 14 loss studies. 15 MS. ZETTLER: Well, Larry, you know 16 our response to your objection in the Fentress 17 court. 18 MR. MYERS: Paul's asking his 19 questions, and she's not going to answer that 20 question, so ask another. 21 MR. SMITH: I'll take any help that I 22 can. 23 MR. MYERS: I understand. 24 MR. SMITH: And her objections are my Page 274 1 objections, and her comments are my comments. 2 MR. MYERS: If you want to make that 3 as a blanket statement, you might want to think 4 about that. 5 MS. ZETTLER: From whose perspective, 6 Larry? 7 Q. All right. When was your next 8 occasion to visit the Food and Drug 9 Administration? 10 A. That was the last one. 11 Q. Did you go down for the 12 September, 1991 advisory committee meeting in 13 connection with the labeling changes on 14 suicidality? 15 A. No. 16 Q. Did you send somebody from 17 your department down for that meeting? 18 A. No. 19 Q. Your department prepared a lot 20 of data for that meeting, didn't they? 21 A. Which department? 22 Q. The department that you were 23 running at the time, September of '91. 24 A. Yes. Page 275 1 Q. And all of that data for the 2 September, 1991 meeting had to do with 3 suicidality and Fluoxetine; correct? 4 MR. MYERS: Before she answers, I 5 object to the form, I think that assumes facts 6 that are not in evidence and never will be. But 7 if you know if that's true or not, tell him. 8 A. I don't know. 9 Q. You know that was the reason 10 that the data was being examined, don't you, to 11 determine whether or not there was any connection 12 between Prozac and suicide? 13 A. Could you repeat your 14 question? 15 (THE COURT REPORTER READ BACK THE 16 REQUESTED TESTIMONY.) 17 A. I know we were reviewing our 18 data that had been collected on Fluoxetine up to 19 a certain point in time with respect to those 20 adverse events. 21 Q. Up to what point in time? 22 A. I don't know what the cutoff 23 date was. 24 Q. Did you assist Doctor Beasley Page 276 1 in his preparation of his meta-analysis that was 2 finally published in the British Medical Journal? 3 A. No. 4 Q. You didn't have anything to do 5 with collecting the data that he used in that 6 meta-analysis? 7 A. I personally did not have 8 anything to do with that. 9 Q. Was that done under your 10 direction by members of your department? 11 A. It was not done under my 12 direction, it would have been done under Doctor 13 Beasley's direction. 14 Q. What was your job in August, 15 1991, Ms. Ashbrook? 16 A. Manager of medical services. 17 Q. And at that time, were you in 18 charge of those individuals that were working in 19 what was known as the drug epidemiology unit? 20 A. I was the manager for that 21 group. 22 Q. All right. And, Ms. Ashbrook, 23 does that mean that you had responsibility for 24 those individuals doing their job? Page 277 1 MR. MYERS: Paul, you asked her this 2 yesterday. I'm going to let her answer one more 3 time. Go ahead and answer him. You had a long 4 discussion with her about this yesterday. Go 5 ahead. 6 A. I was responsible from an 7 administrative sense to see that we had the 8 appropriate people in there, that we recruited 9 the appropriate people, and that people were 10 trained. The direction of the day-to-day work 11 was done by the department head. 12 Q. But that department head 13 reported to you, didn't they? 14 A. Yes. 15 Q. And you held him responsible 16 to see that that work was done; correct? 17 MR. MYERS: She's already answered 18 that. Answer it one more time. 19 A. Yes. 20 Q. And somebody was over you to 21 make sure that you were holding him responsible 22 for seeing that work was done; correct? 23 A. I had someone I reported to, 24 yes. Page 278 1 Q. And who was that? 2 A. Max Talbott. 3 Q. I guess it's a question, Ms. 4 Ashbrook, of accountability, and the 5 responsibility for being accountable for the work 6 done by the individuals in the drug epidemiology 7 unit has to at some point fall at some level; 8 correct? 9 A. Yes. 10 Q. You had that responsibility 11 and that accountability during the time that you 12 were the manager of medical services, didn't you? 13 A. The department head directed 14 what the people did, and the people were the ones 15 who were accountable to get the work done. 16 Q. And you were responsible to 17 ensure that they did that work, weren't you? 18 A. (Witness gives no response.). 19 Q. I'm sorry, I didn't hear your 20 answer. 21 A. The department head was the 22 one who directed the day-to-day tasks. 23 Q. I understand that. I don't do 24 the typing in my office; correct? Page 279 1 MR. MYERS: Don't answer that. Ask 2 another question, Paul. 3 Q. But I'm trying to get an 4 explanation from you and get a question to you by 5 giving you an explanation, all right, so bear 6 with me. I don't do the typing in my office, but 7 I'm responsible for the letter that is mailed; 8 correct? Now there has to be some 9 responsibility, even though the work is not being 10 actually done by me. My question to you is: 11 Weren't you responsible for the work done in the 12 drug epidemiology unit when you were the manager 13 of medical services, even though you didn't 14 actually perform the functions? 15 A. What do you mean by 16 responsible for? 17 Q. In the manner I was trying to 18 give you an explanation for, where I'm 19 responsible for the letter that I send out in my 20 law practice, but I don't actually type that 21 letter. 22 MR. MYERS: He wants to know if you 23 were responsible in the same way that he's used 24 this illustration. Page 280 1 A. No, I was not. 2 Q. Why were you not responsible 3 for the work being done in the drug epidemiology 4 unit? 5 A. In your analogy to the office, 6 as you stated it, it would indicate to me that 7 you created the letter that got typed that went 8 out. To use that same analogy, I did not create 9 the work product that went out. I accepted the 10 responsibility that the drug epidemiology unit 11 would support and respond to what needed to be 12 answered, and I provided the staff to do it. 13 That was my responsibility. 14 Q. Were you responsible to see 15 that the data, as reported by the drug 16 epidemiology unit, was accurate? 17 A. No. 18 Q. Who was, at the time you were 19 the manager of medical services? 20 A. They worked with Doctor 21 Beasley or whoever was the group that pulled it 22 together. 23 Q. So Doctor Beasley was 24 responsible for the accuracy with respect to the Page 281 1 data that was being accumulated and transmitted 2 in the drug epidemiology unit while you were the 3 manager of medical services? 4 A. For that particular project. 5 Q. What particular project? 6 A. The one you've been 7 discussing. 8 Q. I'm not talking about any 9 particular project, I'm talking about the data 10 that was collected and transmitted and assembled 11 and collated and compiled by the drug 12 epidemiology unit while you were the manager of 13 medical services at Eli Lilly and Company. Who 14 was responsible for the accuracy of that 15 information? 16 A. The individuals in the unit, 17 the people that worked with the data day-to-day. 18 Q. And if they made a mistake, it 19 was their mistake, and it wasn't your problem, is 20 that right? 21 MR. MYERS: I object to the form, 22 that's not what she said. But tell him whether 23 he's right or wrong. 24 A. I held the people accountable Page 282 1 for the work that they produced. 2 Q. And you were accountable to 3 your supervisors for the work they produced, 4 weren't you? 5 A. I didn't look at it that way. 6 Q. You didn't feel that you were 7 accountable to Doctor Talbott, your supervisor, 8 for the accuracy of the information being 9 assembled and collected and transmitted by 10 individuals in the drug epidemiology unit? 11 A. The individuals were 12 accountable for that. 13 Q. Each individual, right? 14 A. Yes. 15 Q. Which individuals then? 16 MR. MYERS: You want to know who they 17 were at that point in time, the day you 18 referenced? 19 MR. SMITH: I'm talking about 20 categories of individuals. 21 MR. MYERS: Oh, all right. 22 Q. Wasn't the lady that entered 23 the information into the computer responsible for 24 the accuracy of the information in the computer? Page 283 1 A. That was a starting point. 2 Q. All right. Where was the 3 ending point, then, if that was the starting 4 point, where was the ending point? 5 MR. MYERS: The ending point of what? 6 MR. SMITH: The accountability for the 7 accuracy of the data. 8 A. The CRAs and the physicians 9 that they worked with. 10 Q. Were the physicians 11 responsible to ensure the accuracy of the data in 12 the drug epidemiology unit? 13 A. Physicians reviewed every 14 adverse event on the products they were 15 responsible for with CRAs in the drug 16 epidemiology unit. 17 Q. So if there was an inaccuracy 18 with respect to a particular adverse event, it's 19 the clinical research physician there at Eli 20 Lilly and Company there in Indianapolis that's 21 reviewing that data as it comes in reported 22 either as part of a clinical trial or as a part 23 of some spontaneous report? 24 MR. MYERS: Let me ask a Page 284 1 clarification. When you say an inaccuracy, you 2 mean between the time a piece of information is 3 received and the time it's inputted and takes 4 some other form? 5 MR. SMITH: I'm talking about the 6 context in which she was giving her response, 7 where it was the responsibility of the physicians 8 to review the accuracy of the data with respect 9 to adverse events. 10 MR. MYERS: That isn't what she said. 11 Do you understand the question? 12 THE WITNESS: I would like to have it 13 repeated at this point, please. 14 Q. Be glad to. 15 (THE COURT REPORTER READ BACK THE 16 REQUESTED TESTIMONY.) 17 A. The DEU, CRAs work with the 18 research physicians in the review of the adverse 19 events that came into the drug epidemiology unit. 20 Q. I understand that. That's not 21 my question. My question is: Is it the clinical 22 research physician that's responsible for the 23 accuracy of the data that is reported by the drug 24 epidemiology unit with respect to number, kinds, Page 285 1 and classifications of adverse events in 2 connection with a particular product that Lilly 3 has on the market? 4 A. It's a responsibility between 5 the DEU, CRA, and the research physician. 6 Q. And not you? 7 A. I did not view it as mine. 8 Q. So during the time you were 9 the manager of medical services, and therefore 10 had the drug epidemiology unit under your general 11 supervision, you were not responsible for 12 inaccuracies that might be reported by the drug 13 epidemiology unit, it would be the fault of the 14 clinical physician and the particular CRA 15 involved, and not your fault? 16 MR. MYERS: I object to the form, 17 nobody said anything about fault, but tell him if 18 you know. 19 A. I did not look at the data day 20 to day. 21 Q. I didn't ask you whether you 22 reviewed the data, I'm asking concerning the 23 responsibility for any inaccuracies in the 24 reporting of adverse events that are received and Page 286 1 transmitted by the drug epidemiology unit? 2 A. I did not review it as my 3 responsibility. 4 Q. And you reviewed it as the 5 responsibility of the individual clinical 6 research administrator and the individual 7 clinical physician reviewing each of the adverse 8 events? 9 A. Yes. 10 MR. SMITH: Let's take a quick break. 11 (PLAINTIFFS' EXHIBIT NO. 5 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Have you had an opportunity, 15 Ms. Ashbrook, to review what's been marked as 16 Exhibit No. 5? 17 A. Yes, I have. 18 Q. And do you recall seeing that 19 document before? 20 A. I appear to be a CC on this 21 list, so I assume that it crossed my desk in 22 April of '85. 23 Q. And it was your practice in 24 April of 1985 to read those documents that Page 287 1 crossed your desk, was it not? 2 A. Yes. 3 Q. And it was your practice at 4 that time to keep abreast of the various issues 5 in connection with Fluoxetine and particular 6 adverse events or adverse reactions that might be 7 reported in connection with this drug that you 8 all were studying; correct? 9 A. That I kept abreast of all, 10 did you say, all adverse events? 11 Q. Anything that would have a, 12 what is that, a fifteen-page attachment to it, 13 concerning one particular category of adverse 14 events would be something that would be of 15 interest to you? 16 A. Yes. 17 Q. That's a document that was 18 authored by Doctor C. D. Hardison, is it not? 19 A. Yes. 20 Q. Who is Doctor C. D. Hardison? 21 A. A statistician. 22 Q. Where? 23 A. At that point he was with Eli 24 Lilly and Company. Page 288 1 Q. Is he still with Eli Lilly and 2 Company? 3 A. No. 4 Q. When did he leave Eli Lilly 5 and Company? 6 A. It's been several years ago, I 7 don't recall when. 8 Q. Was he in your group at the 9 time? 10 A. Not in my group, he was a 11 statistician. 12 Q. Doing work in connection with 13 your group, wasn't he? 14 A. Yes. 15 Q. And where is he now? 16 A. I don't know. 17 Q. Where was he when you last 18 were aware of where he was? 19 A. Eli Lilly and Company. 20 Q. You don't know where he went? 21 A. Not off the top of my head. 22 Q. Doctor Hardison was terminated 23 from his employment with Lilly, wasn't he? 24 A. Not that I recall. Page 289 1 Q. Do you recall that he was at 2 least given the opportunity to voluntarily leave? 3 A. No. 4 Q. Do you remember that his work 5 was not considered acceptable by Eli Lilly and 6 Company? 7 A. No. 8 Q. Did you personally know Doctor 9 Hardison? 10 A. Yes. 11 Q. Did you have any complaints 12 with the work that he did in connection with 13 Fluoxetine? 14 A. A statistician, I would have 15 complaint about his work as a statistician. 16 Q. You had complaints about his 17 work as a statistician? 18 A. I'm asking if that's the 19 question. 20 MR. MYERS: That's the question. 21 Q. Yes. 22 A. No. 23 Q. You had complaints about his 24 work in any respect? Page 290 1 A. No. 2 Q. Did you have complaints about 3 his personality or did you have some disagreement 4 with Doctor Hardison concerning anything? 5 A. What do you mean by 6 disagreements? 7 Q. Areas in which you disagreed. 8 A. Not that I recall. 9 Q. Did you like Doctor Hardison? 10 A. Yes. 11 Q. Did you respect him as an 12 individual? 13 A. Yes. 14 Q. And respected him as a 15 statistician? 16 A. Yes. 17 Q. And you have not heard of any 18 criticisms of Doctor Hardison, is that your 19 testimony here, Ms. Ashbrook? 20 A. Yes. 21 Q. Who is Doctor S. Bandak? 22 A. He's a physician. 23 Q. In London? 24 A. At that time, yes. Page 291 1 Q. Where is he now? 2 A. He's in Canada. 3 Q. Is he still working for Lilly? 4 A. Yes, he is, as far as I know. 5 Q. What is his position with 6 Lilly in Canada? 7 A. Medical director. 8 Q. Of Canadian operations or the 9 Canadian affiliate? 10 A. Yes. 11 Q. And J. -- Doctor J. Schenk, 12 at Bad Homburg, you're not sure where -- is it a 13 he or a she? 14 A. She. 15 Q. Where she is now. 16 A. No. 17 Q. You know she's no longer with 18 Lilly. 19 A. I know she left Lilly. As far 20 as I know, she has not been reemployed. 21 Q. That document indicates that 22 in April of 1985 there was an issue concerning 23 suicide attempt rates at the time; correct? 24 A. Yes, that's what the title Page 292 1 says. 2 Q. And it indicates that there 3 was a London meeting on March 21st, 1985, is that 4 right? 5 A. That's what the note says. 6 Q. Apparently Doctor Hardison, 7 the statistician, was meeting with -- had met 8 with Doctor Bandak and Doctor Schenk, who are 9 medical doctors in London; correct? 10 Q. That's what -- well, that's 11 the major addressees on this memo, and he refers 12 to a London meeting, as agreed upon at our London 13 meeting. 14 Q. It says our London meeting, 15 which leads me to the conclusion that the three 16 of them had met in London. 17 A. Based on what I read here, I 18 would come to the same conclusion. 19 Q. All right. Apparently at that 20 time there were patients who were attempting or 21 completing suicide while on Fluoxetine. 22 A. That's what this document is a 23 review of. 24 Q. And what did you do in Page 293 1 response to that document in connection with your 2 job duties as, I believe at that time, you were 3 the project leader of the Fluoxetine group, 4 weren't you? 5 A. Yes. 6 Q. What did you do in response or 7 in connection with that memo, if anything? 8 A. This was a summary to the one 9 question from the BGA. 10 Q. Beg your pardon? 11 A. This was was a summarization 12 of the response to one of the questions from the 13 BGA. 14 Q. All right. 15 A. So I probably took the 16 response and put it in with all the other 17 questions so we could respond to them. 18 Q. All right. So because of 19 these issues that the BGA had raised, apparently 20 Lilly had sent a statistician to meet with these 21 physicians in London to discuss a response to 22 those issues presented by the BGA, is that right? 23 A. That's what this cover memo 24 states. Page 294 1 Q. Do you recall that occurring? 2 A. No, I don't. 3 Q. And a summary was prepared, 4 and you think that was used in responding to the 5 BGA concerns? 6 A. Yes. 7 Q. Who is Dorothy S. Dobbs, M.D.? 8 A. She was a regulatory 9 scientist. 10 Q. A what? 11 A. Regulatory scientist. 12 Q. All right. What was her job 13 in connection with Fluoxetine? 14 A. She was the regulatory person 15 that was initially involved with Fluoxetine. 16 Q. Was she the regulatory 17 scientist initially involved with Fluoxetine at 18 the time you came on to the Fluoxetine project? 19 A. No. 20 Q. When did she come on? 21 A. Somewhere prior to the 22 submission of the new drug application. 23 Q. And she became a member of the 24 Prozac Fluoxetine team? Page 295 1 A. She was the regulatory 2 representative, but she didn't work for me, she 3 was in regulatory. 4 Q. I understand that, but was she 5 part of the Fluoxetine team? 6 A. What do you mean by part of 7 the team? 8 Q. The team you were the group 9 leader of. 10 A. She was a regulatory 11 representative that worked with regulatory issues 12 or questions, we would go to her. 13 Q. My question simply is: Was 14 she part of the team? 15 MR. MYERS: She answered. Your first 16 question was she part of the team of which she 17 was a project leader. She answered that question 18 about three or four questions ago, she said she 19 didn't work for me but she was in regulatory. 20 Now she's clarifying it. 21 MR. SMITH: I understand that. 22 Q. But whether she's in 23 regulatory or on the board of directors, was she 24 part of the Fluoxetine team? Page 296 1 A. I go back to -- by team you 2 mean -- what do you mean by team? 3 Q. The team that you were the 4 project leader of. You were the one that used 5 team first. 6 MR. MYERS: I object to the question, 7 I think she's answered it. 8 Q. It's not a difficult question, 9 Ms. Ashbrook. Was Dorothy Dobbs part of the 10 Fluoxetine project team that you were the project 11 leader of? 12 A. I was only the project leader 13 over the paramedical support group, I was not the 14 project leader responsible for all other aspects 15 of Fluoxetine. 16 Q. But when you came on, it was a 17 small group of people, wasn't it? 18 A. Yes. 19 Q. My question doesn't have any 20 sinister motives, it's not designed to trick you. 21 My question is: Was she part of the team working 22 on Fluoxetine? 23 A. She was a -- 24 Q. Whether she was in regulatory Page 297 1 or somewhere else is of no import to me. 2 A. I worked with her for 3 regulatory issues with respect to Fluoxetine. 4 Q. Because you worked with her on 5 regulatory issues with respect to Fluoxetine, did 6 you consider her a member of the Fluoxetine 7 project team? 8 A. She was part of our working 9 group, she was our resource. 10 Q. How long did Dorothy Dobbs 11 continue as a regulatory scientist working on 12 Fluoxetine? 13 A. I know she was there for the 14 initial submission of the new drug application. 15 I don't know for how long she remained with the 16 project, for a while afterwards, I can't name 17 dates. 18 Q. But it was some date after 19 September, 1983 when the submission was made? 20 A. Yes. 21 Q. And how long did she continue 22 as an employee of Lilly? 23 A. As I just stated, it was 24 sometime after '83. For how long, I don't Page 298 1 recall. 2 Q. Well, did she move off 3 Fluoxetine work and on to some other project, and 4 leave, or was she still working on Fluoxetine 5 when she left? 6 MR. MYERS: The company? 7 MR. SMITH: Yes. 8 MR. MYERS: That's what he wants to 9 know. 10 A. She had other 11 responsibilities. Whether that replaced or was 12 in addition to, I don't recall. 13 Q. Did you ever have any problems 14 with Doctor Dobbs in connection with the 15 submission of the Fluoxetine NDA? 16 A. What do you mean by problems? 17 Q. Any problems in getting her to 18 accept the submission as it was going to be 19 presented to the Food and Drug Administration? 20 A. Did I personally have any 21 problems? 22 Q. Or anyone within your group. 23 A. Not that I recall. 24 Q. Did you and Doctor Dobbs get Page 299 1 along? 2 A. Yes. 3 Q. Did you ever issue any 4 criticism of her work, either orally or in 5 writing, Ms. Ashbrook? 6 A. Not that I recall. 7 Q. Do you know whether she 8 expressed any criticism of your work, either 9 orally or in writing? 10 A. Not that I'm aware of. 11 Q. Do you recall any discussions 12 that you and she or she and any member of your 13 team might have had in connection with suicide, 14 suicide attempts or suicidal ideation? 15 A. Well, in the preparation of 16 the submission, we had the one patient that had 17 committed suicide while on the placebo wash-out 18 period, so we may have had a discussion that that 19 was written up and reviewed. 20 Q. Any other discussion that 21 comes to mind? 22 A. Not that I recall. 23 Q. Where is Doctor Dobbs now? 24 A. She was down -- went back to Page 300 1 Georgia. 2 Q. Is that where she was from? 3 A. That's where she went. I 4 don't know if that's where she immediately came 5 from before she joined Lilly, but that's where 6 she went, so she had some -- I don't know if she 7 was really from there or lived there or anything. 8 Q. You said she went back to 9 Georgia. 10 A. Okay. She went to Georgia, 11 I'm sorry. 12 Q. Aren't we lawyers irritating 13 in connection with that? 14 MR. MYERS: I hope to go back to 15 Georgia sometime today, but I'm not from Georgia, 16 how about that. 17 Q. Where in Georgia was it your 18 understanding that she was going to? 19 A. Smyrna. 20 Q. Smyrna? 21 A. Smyrna, Georgia. 22 Q. Smyrna, Georgia? 23 MR. MYERS: Smyrna, Georgia, Smyrna, 24 Tennessee, Smyrna, Alabama. Page 301 1 Q. When did you last talk to 2 Doctor Dobbs? 3 A. Verbally, probably around when 4 she left Lilly. 5 Q. You haven't kept up with her 6 since she left Lilly? 7 A. We exchange Christmas cards. 8 Q. Have you received a Christmas 9 card from her yet this year? 10 A. No. 11 Q. Do you happen to remember 12 where she was when you got the Christmas card 13 from her last year? 14 A. Smyrna. 15 Q. Okay. I thought since she 16 left in the '80s, she might have moved even since 17 she went to Smyrna. But you don't know? 18 A. No. 19 Q. Doctor Dobbs did author the 20 safety and efficacy portions of the submission to 21 the Food and Drug Administration of September of 22 1983, didn't she? 23 A. What do you mean by authored? 24 Q. She was responsible for that Page 302 1 portion of that document. 2 MR. MYERS: That's a different 3 question maybe. 4 A. Yes, I guess what -- 5 Q. I'm just trying to clarify the 6 question. 7 MR. MYERS: I think he wants to know 8 what her responsibility was for the safety and 9 efficacy portion. 10 A. She was our regulatory 11 contact, and I worked very closely with her as 12 these documents were prepared. She had the final 13 review of them. 14 Q. I understand that, but I'm 15 looking at a table of contents, and I will be 16 glad to show you. I didn't think it was going to 17 be that significant an issue, but since you 18 prepared it, I thought you wouldn't need to see 19 it, but we'll show it to you. 20 (PLAINTIFFS' EXHIBIT NO. 6 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 Q. Let me show you what's been 24 marked as Exhibit 6. Page 303 1 MR. MYERS: Let me see it. Make sure 2 it hasn't been tampered with. 3 Q. I'll ask you to look at that 4 and tell me if that's not a memo dated in 5 January, 1983 from you? 6 A. Yes, this is from me. 7 Q. And it has a table of contents 8 there with it, doesn't it, for the submission to 9 the Food and Drug Administration? 10 A. This was the proposed table of 11 contents for our submission. 12 Q. Out at the left-hand side of 13 the page there's names of individuals who I 14 assumed would be responsible for or in charge of 15 particular sections of the submission, is that 16 not what that is? 17 A. Yes. 18 Q. That is what it is? 19 A. Yes. 20 Q. And doesn't it have Doctor 21 Dobbs there as responsible for particular areas, 22 and other individuals there responsible for 23 particular areas? 24 A. Yes. Page 304 1 Q. And isn't Doctor Dobbs listed 2 in that area where it says safety conclusions? 3 A. Yes. 4 Q. Do you recall, other than that 5 one incident, you and she discussing whether or 6 not there should be some suicide issues submitted 7 in the September, 1983 submission to the Food and 8 Drug Administration? 9 A. What one incident? 10 Q. The one incident where you 11 mentioned that somebody committed suicide during 12 the wash-out period before they had gotten any 13 medicine. 14 A. Not that I recall. 15 Q. Was Doctor Dobbs terminated 16 from Lilly or did she voluntarily resign her 17 position with Lilly? 18 A. I know she left the company. 19 Q. I know she left the company, 20 too, that's not what my question was. Was she 21 terminated from Lilly or did she voluntarily 22 resign? 23 A. As far as I know, she 24 resigned. Page 305 1 Q. Do you know whether she was 2 asked to resign? 3 A. No, I do not know that. 4 MR. SMITH: I pass the witness. 5 MR. MYERS: I have never been so 6 excited to see Nancy start asking questions. 7 * * * * * * * * * * 8 CROSS EXAMINATION 9 BY MS. ZETTLER: 10 Q. I introduced myself yesterday. 11 My name is Nancy Zettler, and I represent a 12 number of plaintiffs in the Fentress versus Shea 13 Communications case in Louisville, Kentucky which 14 stems from the shootings by Joseph Wesbecker in 15 September of 1989. Are you familiar with the 16 Wesbecker incident? 17 A. I have heard of it, yes. 18 Q. What have you heard about that 19 incident? 20 A. That he shot several people. 21 I don't recall if it was his area, former area of 22 employment, or what, but I know that he shot 23 people. 24 Q. Have you heard anything else Page 306 1 about that incident besides that Mr. Wesbecker 2 shot some people? 3 A. At one point he has taking 4 Fluoxetine for his depression. 5 Q. Anything else? 6 A. That's, I mean, the highlights 7 that I recall. 8 Q. Okay. In September of 1989, 9 where were you within the company? I apologize. 10 I wasn't here when you guys started yesterday, so 11 I'm not familiar with your employment history at 12 Lilly. 13 A. Okay. I was a department head 14 in medical information systems. 15 Q. What is medical information 16 systems? 17 MR. MYERS: I know, Nancy, she'll tell 18 you where she was, but Paul went over this ad 19 nauseum, so please try to keep this down. 20 MS. ZETTLER: I will, I just want to 21 get an idea. 22 Q. What was -- what is medical 23 information systems? 24 A. It's the systems analysts that Page 307 1 work in medical on creating data entry systems 2 for clinical trials and designing and obtaining 3 the output from our clinical trials. 4 Q. Computer operators, computer 5 people? 6 A. Systems analysts. 7 Q. Anything else, medical 8 writing, is that involved in that area? 9 A. No. 10 Q. Any other -- besides systems, 11 anything else? 12 A. No. 13 Q. So in September of 1989 you 14 were the department head of that area? 15 A. (Witness moves head up and 16 down.). 17 MR. MYERS: Yes. 18 A. Yes. 19 Q. Did your department have any 20 responsibilities with regards to the Joseph 21 Wesbecker incident in September of 1989? 22 A. Did the people I have 23 responsibility for have any, no. 24 Q. Did you personally have any Page 308 1 direct involvement in gathering information or 2 related in any way to the Joseph Wesbecker 3 incident? 4 A. No. 5 Q. At any time? 6 A. No. 7 Q. Initially I have a few 8 follow-up questions to what Paul asked you 9 yesterday, so I'm going to jump around a little 10 bit so bear with me, and if you don't understand 11 something, please let me know and I'll rephrase 12 the question, okay? 13 MR. MYERS: She's been cautioned. 14 Q. Been cautioned about how fast 15 I talk? 16 A. Yes. 17 Q. Well, I'm really making an 18 effort to try to slow down. So if I get going, 19 let me know and I'll slow down. 20 A. Okay. 21 Q. To your knowledge did Doctor 22 Hardison have any criticisms of any work that was 23 being done at Lilly with regards to Fluoxetine 24 while he was there? Page 309 1 A. Not that I'm aware of. 2 Q. Do you know why he left Lilly? 3 A. No. 4 Q. How about Doctor Dobbs, to 5 your knowledge did she have any criticism with 6 any work that was being done at Lilly with 7 regards to Fluoxetine? 8 A. Not that I am aware of. 9 Q. Doctor Dobbs used to be with 10 the FDA; is that correct? 11 A. Yes. 12 Q. Do you remember what position 13 she held there? 14 A. No. 15 Q. Do you know why she left 16 Lilly? 17 A. I don't think her career 18 opportunities were being fulfilled that she had 19 anticipated. 20 Q. What career opportunities had 21 she anticipated at Lilly? 22 A. I don't know for sure what 23 they were. I think she was -- when she took the 24 job, she was promised maybe a position at a Page 310 1 certain time or whatever, it did not happen. 2 Q. What position? 3 A. I don't know. 4 Q. Would it have been a promotion 5 over what she was doing at the time that she 6 left? 7 A. Probably. 8 Q. What was her title within 9 regulatory while you worked with her? 10 A. Again, I thought she was a 11 regulatory scientist, I don't know if that was 12 her official title. 13 Q. Was she hoping to be the head 14 or manager of that department at some period of 15 time? 16 A. Was she what? 17 Q. Hoping to become manager, the 18 head of that regulatory department at some time? 19 A. I don't remember what area it 20 was. 21 Q. How is it that you became 22 aware that she was, first of all, hoping to 23 achieve promotion within the department that she 24 worked at Lilly? Page 311 1 A. When did I first become aware? 2 Q. Let me ask it this way: How 3 is it that you became aware that she had certain 4 career goals at Lilly that she wanted to achieve? 5 A. Personal conversations. 6 Q. When did this conversation 7 take place? 8 A. I don't recall. 9 Q. Was it towards the end of her 10 tenure at Lilly? 11 A. I don't recall. 12 Q. How is it you became aware 13 that she was not going to achieve the career 14 goals that she had set for herself at Lilly? 15 A. That I became aware? 16 Q. Right. 17 A. I did not become aware. 18 Q. You just testified that you 19 felt that one of the reasons that she left was 20 that she was not going to obtain a position that 21 she had thought she would at Lilly; correct? 22 A. That's what she felt. 23 Q. Okay. So I'm just asking 24 where you got your information. So that came Page 312 1 from her? 2 A. Yes. 3 Q. Do you know why she wasn't 4 going to achieve the position that she was hoping 5 to achieve? 6 A. No. 7 Q. Just so I'm not confused, it's 8 your recollection that she was promised a certain 9 position at Lilly eventually and learned later 10 that she was not going to achieve that position? 11 A. I doubt that anything was in 12 writing. So promised, I don't know if that's the 13 appropriate word. 14 Q. But she was under the 15 impression? 16 A. She was under the impression. 17 Q. You have to let me finish my 18 questions because Kathy can't take us both. She 19 was -- at least to your knowledge, she was under 20 the impression that she was going to achieve a 21 certain position at Lilly, and then later became 22 aware that she was not going to achieve that 23 position; correct? 24 A. Yes. Page 313 1 Q. Yesterday you testified that 2 Doctor Weber, Hans Weber, was here in the United 3 States for a two-year period of time, I believe? 4 A. For a period of time he was 5 here, I don't know how long. 6 Q. Do you know why he was here? 7 A. Why? 8 Q. Right. 9 A. No, not really. 10 Q. Do you know what he was doing 11 while he was here? 12 A. Yes. 13 Q. What was he doing? 14 A. He was here in the United 15 States as a representative in the international 16 group. 17 Q. When you say international 18 group, what do you mean? 19 A. There were physicians that 20 liaised with our affiliates if they had issues -- 21 you know, to discuss our products. So rather 22 than the affiliates needing to contact several 23 different people, they would know there was one 24 person that was responsible, either by country or Page 314 1 by therapeutic class, that they could call, and 2 then this international group would network among 3 the rest of them to be able to work to get 4 whatever information they needed or help or 5 whatever. 6 Q. Was there an international 7 Fluoxetine group? 8 A. In and of and by itself? 9 Q. Right. 10 A. Not that I recall. 11 Q. This international group that 12 you're talking about, is it a department or a 13 group in and of itself? 14 A. It was. 15 Q. Is it still? 16 A. No. 17 Q. When was the group disbanded? 18 A. Two to three years ago. 19 Q. Do you know why it was 20 disbanded? 21 A. There was a reorganization. 22 Q. What was Doctor Webber's 23 responsibility as a member of the international 24 group? Page 315 1 A. What do you mean what were his 2 responsibilities? 3 Q. What were his specific 4 responsibilities? You said that some members of 5 this group acted liaisons to the outside the 6 United States affiliates, right? 7 A. Yes. 8 Q. Did he have responsibility for 9 any particular affiliates, for instance? 10 A. I don't know that. 11 Q. Do you know if he had any 12 responsibilities with regards to the German 13 affiliate while he was here in the United States? 14 A. I don't know for a fact. 15 Q. Did you work with Doctor Weber 16 while he was here in the United States? 17 A. Not really. 18 Q. Did anybody under your control 19 work for Doctor Weber while he was here in the 20 United States? 21 A. Work for him? 22 Q. With him, in any capacity? 23 A. I don't know for sure exactly 24 when he was over here, what years he was, so not Page 316 1 that I specifically recall. 2 Q. Was it common for Lilly to 3 bring people from the outside affiliates to 4 Indianapolis to work in the international group? 5 A. Yes, there was -- yes, 6 cross-functional, bringing people over here for a 7 while, yes. 8 Q. To your knowledge did Doctor 9 Weber ever have any criticism with the way that 10 Fluoxetine information was gathered or reported 11 to regulatory authorities by Lilly? 12 A. While he was over here for 13 that period of time? 14 Q. At any time. 15 A. Could you repeat the question? 16 Q. Sure. To your knowledge has 17 Doctor Hans Weber ever had any criticisms with 18 the way that Lilly gathered or reported 19 Fluoxetine data to regulatory agencies? 20 A. I know he had asked for 21 additional information to be able to meet the 22 regulations that Germany has. 23 Q. And that's -- those questions 24 are related to the documents that Paul talked Page 317 1 with you about yesterday, and earlier today? For 2 example, Exhibit 5? 3 A. What was your -- I'm sorry? 4 Q. Okay. Why don't you do this, 5 take a look at Exhibit 4 also. Yesterday you 6 talked with Paul about the issue of questions by 7 the BGA regarding Fluoxetine in the course of the 8 registration procedure. 9 A. Correct. 10 Q. And a couple of seconds ago 11 you told me that to your knowledge Doctor Weber 12 had asked for additional information. 13 A. Yes. 14 Q. The additional information 15 that he asked for, is that reflected in Exhibit 16 4? 17 A. Yes. 18 Q. Besides the information that's 19 reflected in Exhibit 4, has Doctor Weber, to your 20 knowledge, asked for any other information 21 regarding Fluoxetine? 22 MR. MYERS: In order to make some kind 23 of report or compliance with? 24 MS. ZETTLER: No, anything. Page 318 1 A. Well, the German -- I'm aware 2 from when I had the drug epidemiology unit that 3 the German regulations have changed with 4 reporting of adverse events on products, and it's 5 different than what we need to report here in the 6 United States, so he's asked for additional 7 information. 8 Q. Okay. Besides the information 9 that's reflected it Exhibit 4, the questions 10 reflected in Exhibit 4, and Doctor Weber's 11 request for additional information to comply with 12 the German regulatory changes -- 13 A. Right. 14 Q. -- has Doctor Weber asked for 15 any other information to your knowledge? 16 A. Not to my knowledge. 17 Q. Besides the information that 18 he's requested that you have knowledge of, has he 19 had any criticism about the way that Fluoxetine 20 information was gathered by Lilly or anybody on 21 behalf of Lilly? 22 A. No. 23 Q. To your knowledge has he had 24 any criticisms about the way that safety Page 319 1 information was reported by Lilly to the various 2 regulatory agencies? 3 A. Has he had any criticism? 4 Q. Right. 5 A. Other than this document and 6 what I had shared with you, that's as far as I 7 can comment. 8 Q. Yesterday while we were 9 talking about Exhibit 4, I believe you testified 10 that it was a concern at Indianapolis as to 11 whether or not there was an understanding as to 12 what the BGA was asking for; correct? 13 A. Yes. 14 Q. And what the BGA was asking 15 for was transmitted to Indianapolis through the 16 German affiliate, including Doctor Weber; 17 correct, at least as reflected in Exhibit 4? 18 A. Yes. 19 Q. Tell me a little bit about the 20 German affiliate's role in the development and 21 testing of Fluoxetine. In other words did they 22 have responsibility over monitoring clinical 23 trials that were being conducted in Germany? 24 A. If there were clinical trials Page 320 1 conducted in Germany, they would monitor those. 2 Q. Do you have an understanding 3 as to whether or not any clinical trials were 4 being conducted in Germany in the early to 5 mid-'80s? 6 MR. MYERS: On Fluoxetine? 7 MS. ZETTLER: On Fluoxetine. 8 A. There were clinical trials 9 that were initiated, and I'm going to say it was 10 mid -- it was past the submission of -- the 11 initial submission to the NDA before any of those 12 studies were initiated. 13 Q. Okay. 14 A. As I recall. 15 Q. But in the early to mid-'80s, 16 there were clinical trials on Fluoxetine that had 17 at least begun; correct? 18 A. If you call early as after 19 1983, I would say mid-'80s. 20 Q. Around the same time as the 21 date of Exhibit 4, 1984. 22 A. Possibly. 23 Q. To your knowledge were there 24 any differences in the ways that the clinical Page 321 1 trials were conducted outside the U.S. as 2 compared to the way the clinical trials were 3 conducted in the United States, and again, 4 Fluoxetine clinical trials? 5 A. What do you mean by 6 differences in how they were conducted? 7 Q. Were there differences in the 8 way the information was gathered, patient 9 information, for instance? 10 A. It was gathered on case report 11 forms, I don't know what the case report forms 12 looked like that they gathered it on. 13 Q. Were there similar psychiatric 14 rating scales used in the studies, to your 15 knowledge? 16 A. I don't know. 17 Q. Did you have any 18 responsibility in 1984 for clinical trials run 19 outside the United States on Fluoxetine? 20 A. We helped set up one new case 21 study, and I worked with Doctor Bandak to set up 22 the study. They wanted input from the U.S. on 23 how to conduct the large clinical trials, so I 24 helped with that. We also had initiated, but I Page 322 1 personally didn't have responsibilities, for a 2 USIND study that was conducted in Canada, but 3 that was the extent of my involvement with 4 studies outside the U.S. 5 Q. Lilly would want the 6 information that was gathered from the various 7 depression studies done across the world to be 8 consistent, at least in form, would it not? 9 A. We would want it to be at 10 least consistent in form is your question? 11 Q. Right. 12 A. Yes, we would have wanted 13 that. 14 Q. Okay. And to your knowledge, 15 Doctor Weber was a psychiatrist, was he not, or 16 is a psychiatrist? 17 A. Not that I'm aware. 18 Q. He's not? 19 A. I don't know. 20 Q. He's a medical director in 21 Germany at this time, is he not? 22 A. Yes, he is, and he is a 23 physician. 24 Q. Do you have any recollection Page 323 1 as to whether or not the concerns that Lilly in 2 Indianapolis had regarding the BGA's request, as 3 far as what they were actually requesting, were 4 satisfied or were relayed? 5 A. Could you repeat that? 6 Q. Sure. Yesterday you were 7 telling Paul that you weren't sure that Lilly of 8 Indianapolis wasn't sure when this memorandum 9 reflected in Exhibit 4 came in as to what the BGA 10 was actually asking for; correct? 11 A. That's correct. 12 Q. Do you recall whether or not 13 it was ever clarified what the BGA was asking for 14 in that exhibit? 15 A. Yes. 16 Q. Were you aware of any 17 clarifications that were made in what the BGA was 18 asking for that are different than what is 19 reflected in Exhibit 4, in other words were terms 20 defined, things of that nature? 21 A. Yes. 22 Q. Okay. I believe that Paul was 23 asking you about paragraph ten on the second page 24 of that exhibit? Page 324 1 A. Yes. 2 Q. Was hypnotics, as it's set out 3 in paragraph ten, defined? 4 A. It was or it had to have been 5 so we could respond to it, because we needed 6 specific concomitant medication so we could 7 review the data base to see if those drugs had 8 been taken concomitantly with our patients in the 9 studies. 10 Q. Okay. How about 11 Benzodiazepines, was that defined? 12 A. I would think that it would 13 have been, again because there are several, which 14 ones were they interested in, which ones were 15 marketed. We didn't know, we needed to be able 16 to have specific drug names to go back and search 17 the data base to respond to their questions. 18 Q. So with regards to hypnotics 19 and Benzodiazepines, it wasn't really a problem 20 with which classes of drugs those were, it was 21 more of a problem as to which particular drugs 22 within those classes; correct? 23 A. Right. 24 Q. Were a limited number of Page 325 1 hypnotics referred to by the BGA, in other words 2 were there certain hypnotics they asked for 3 information on and not others? 4 A. I don't recall what the 5 specific drugs were. 6 Q. Is that reflected anywhere in 7 the document as far as you know, is there a 8 listing of what hypnotics the BGA was interested 9 in? 10 A. Again, I would imagine it was 11 reflected in the data that we supplied in 12 response to the BGA. 13 Q. Same for the Benzodiazepines 14 that they were interested in? 15 A. Yes. 16 Q. Were you involved at all, 17 directly or indirectly, with putting together the 18 response to the BGA? 19 A. I was the one who ended up 20 collating everything coming in to make sure we 21 responded to each one of the questions. Did I 22 actually get involved in creating that, probably 23 maybe -- probably from a review standpoint. But 24 as far as to the meat, that was really with the Page 326 1 physician because these were medical issues, and 2 then the statisticians and systems analysts that 3 had to provide the data and do the analysis. 4 Q. But you have seen the actual 5 responses? 6 A. Yes, I had seen them before 7 they were submitted. 8 Q. How voluminous are they, is it 9 one small three-page response or is it a couple 10 of volumes? 11 A. I think it was one to two 12 volumes. 13 Q. How about the next portion of 14 paragraph ten, the paragraph generally asks about 15 comparative use of concomitantly taken hypnotics 16 and Benzodiazepines in agitated slash retarded 17 Fluoxetine patients as well as agitated slash 18 retarded patients on comparitor drugs; correct? 19 A. Yes, that's what it says. 20 Q. Paul asked you a couple of 21 questions yesterday as to whether or not you were 22 aware of any studies that had been done on, I 23 guess it was, specific to this issue, the use of 24 hypnotics and Benzodiazepines in agitated Page 327 1 retarded Fluoxetine patients as opposed to 2 agitated retarded patients on comparitors. Do 3 you remember that? 4 MR. MYERS: I object to the form. He 5 read the thing verbatim at least once or twice 6 and said didn't you do this, didn't you think 7 about it. 8 Q. Do you recall testifying that 9 there were no studies to your knowledge that were 10 done? 11 A. There were no studies with 12 those specific objectives designed. 13 Q. Were you aware of any studies 14 that were done or have been done to date 15 regarding agitated retarded depressed patients 16 generally and the use of Fluoxetine? 17 A. While I had responsibility for 18 Fluoxetine, I do not recall a study initiated 19 with respect to that. 20 Q. How about since you have had 21 responsibility with Fluoxetine? 22 A. I wouldn't know. 23 (PLAINTIFFS' EXHIBIT NO. 7 WAS 24 MARKED FOR IDENTIFICATION AND Page 328 1 RECEIVED IN EVIDENCE.) 2 Q. Have you had a chance to 3 review Exhibit 7? 4 A. Briefly. 5 Q. Does that refresh your 6 recollection as to whether or not any studies had 7 been performed on agitated retarded depression 8 patients using Fluoxetine? 9 A. This is the first time I've 10 seen this. 11 Q. Is there a date on that? 12 A. That's what I was looking for. 13 The date at the foot of the written part is 14 January 11, 1990. 15 Q. Okay. Do you have any idea 16 why that would have been produced as having been 17 part of your file, Ms. Ashbrook? 18 A. This was part of my file? 19 Q. It was produced as part of 20 your file. 21 A. By then my files had been left 22 with the Fluoxetine group because at that point I 23 was in medical information systems, so I had left 24 my files in the Fall of 1988. Page 329 1 Q. So the answer is you have no 2 idea why it would have been produced as part of 3 your file; correct? 4 A. That's correct. 5 Q. How about suicide studies that 6 were done prior to 1990, and I'm not talking 7 about necessarily whether or not people become 8 suicidal on Fluoxetine, but any suicide related 9 study that was done by Lilly on patients using 10 Fluoxetine prior to 1990. 11 A. As that as an objective, I do 12 not recall any studies being done like that. 13 Q. How about a suicide 14 prophylaxis study using Fluoxetine on depressed 15 patients? 16 A. I'm not aware of that. 17 Q. Have you heard of a Doctor 18 Montgomery? 19 A. Yes. 20 Q. Who is Doctor Montgomery? 21 A. He's from the UK. 22 Q. Is he a Lilly employee in the 23 UK? 24 A. No. Page 330 1 Q. Is he a clinical investigator 2 employed by Lilly in the UK? 3 A. He's an investigator that has 4 conducted studies for Lilly. 5 (PLAINTIFFS' EXHIBIT NO. 8 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Have you had a chance to 9 review Exhibit 8? 10 A. Yes, I have. 11 Q. Can you tell me what that 12 exhibit is? 13 A. It indicates that it's a 14 summary of Montgomery protocol entitled 15 Fluoxetine/Placebo: Suicide 16 prophylaxis-personality disorder. 17 Q. Does this refresh your 18 recollection as to whether or not any suicide 19 studies were done or at least initiated prior to 20 1990? 21 A. No, it doesn't. From my 22 recollection, this status says 27, July of '90. 23 I had been gone from the area. 24 Q. For how long at that point? Page 331 1 A. I left in the Fall of 1988. 2 Q. You don't recall hearing 3 anything about a proposed suicide prophylactic 4 study or anything like that? 5 A. No. 6 Q. Do you have idea why this 7 would have been produced as part of your files? 8 A. Again, I left my files with 9 the department when I left. 10 Q. So again, the answer is no, 11 you have no idea why it would have been produced 12 as part of your files? 13 A. I have no idea why it was part 14 of my documents. 15 Q. Going back to Exhibit 4, 16 paragraph ten, was it your recollection -- 17 MR. MYERS: Hold on. 18 A. I don't have it. 19 Q. To your recollection was Lilly 20 able to provide the BGA with information to 21 respond to the questions set out in paragraph 22 ten? 23 A. We responded to each one of 24 their questions. Page 332 1 Q. Okay. Do you recall what 2 Lilly's response to paragraph ten was? 3 A. No. 4 Q. Do you have any recollection 5 of there being a problem between the BGA and the 6 Lilly German affiliate and/or Indianapolis as to 7 what the word concomitant or concomitantly taken 8 hypnotics is, not which hypnotics, but what the 9 term -- 10 A. Hypnotic meant? 11 Q. Right. 12 A. Not that I recall. 13 Q. How about Benzodiazepines, was 14 there a confusion to -- other than what specific 15 Benzodiazepines were referred to, was there a 16 question or confusion as to what the term 17 Benzodiazepine meant between the BGA and Lilly? 18 A. Not that I recall. 19 Q. How about side effect profile, 20 other than what the specifics of the side effect 21 profile may have been, was there a problem to the 22 best of your recollection as to an understanding 23 between Lilly and the BGA as to what the BGA 24 meant by side effect profile? Page 333 1 A. Would you restate that? 2 Q. Other than what the actual 3 side effects may have been in a side effect 4 profile, to your recollection was there a 5 confusion as to what the term side effect profile 6 meant between the BGA and Lilly? 7 A. At this point in time, I don't 8 recall. 9 Q. So the BGA's definition of 10 side effect profile, without the specifics of 11 what might have been included in Fluoxetine's 12 specific side effect profile -- I forgot the 13 first part of my question. 14 MS. ZETTLER: Could you read that 15 back? 16 (THE COURT REPORTER READ BACK THE 17 REQUESTED TESTIMONY.) 18 Q. May have been different than 19 that of Lilly's? 20 MR. MYERS: I object. She said she 21 didn't recall if there was any confusion. She 22 answered it. Tell her again. 23 A. At that point in time, I 24 wasn't aware of any issues. Page 334 1 Q. How about the term suicide or 2 suicide attempt, to your knowledge was there a 3 confusion as to what was meant by suicide or 4 suicide attempt by the BGA? 5 A. Not that I recall. 6 Q. Other than what you already 7 testified to as to which hypnotics and 8 Benzodiazepines the BGA was referring to in 9 paragraph ten, do you recall any other specific 10 clarifications that needed to be made for any of 11 the questions reflected in Exhibit 4? 12 A. I didn't hear the last. 13 Q. Do you recall any specific 14 corrections or clarifications that had to be made 15 with regards to the issues raised in Exhibit 4, 16 other than what you already talked about? 17 MR. MYERS: She's talking about the 18 whole exhibit now. 19 A. The whole exhibit. 20 Q. Go ahead and take a look at it 21 if you need to. 22 A. I know we had a discussion on 23 every single question to make sure it was 24 clarified. Non-endogenous subtype, we needed Page 335 1 clarification on what that was. What was their 2 definition of reactive depression. 3 Q. Okay. 4 A. And from the criteria that we 5 utilize in the U.S. versus what they may have 6 meant, we wanted to make sure there was a 7 commonality of understanding. 8 Q. Okay. To your knowledge is 9 Exhibit 4 a verbatim word-for-word transmission 10 or translation of the BGA's actual request, or is 11 this something that was conveyed by Doctor Weber 12 as to his understanding of what they were 13 requesting? 14 A. As I understand, it is how he 15 has conveyed it to the U.S. affiliate. 16 Q. To your knowledge, would 17 Doctor Weber's understanding of these various 18 terms, such as, quote, reactive depression, 19 unquote, which is set out in paragraph one, be 20 different than individuals at Lilly's 21 understanding of that term? 22 MR. MYERS: Before she answers, I 23 object to the form. That requires a lot of 24 speculation as to what Doctor Weber and other Page 336 1 people at Lilly think. If you know for a fact, 2 tell her. 3 A. I do not know. That gets into 4 the realm of psychiatry and medicine. 5 Q. To your knowledge were the 6 outside the U.S. affiliates provided with Lilly 7 training manuals and policy manuals and things of 8 that nature with regards to their conduction or 9 monitoring of clinical trials? 10 A. At that point, a lot of those 11 were being developed. When they were developed 12 they were distributed. 13 Q. Okay. While those were being 14 developed, what was done to provide the various 15 affiliates and clinical investigators with 16 guidelines or guidance as to how Lilly wanted 17 information generated on Fluoxetine clinical 18 trials or collected through adverse event terms? 19 A. Could you break that down to 20 smaller questions, please? 21 Q. I'm curious in 1984 if the 22 manuals are in the process of being developed, 23 okay? 24 A. They may have -- again, I'm Page 337 1 not going to be able to equate time frames. 2 MR. SMITH: You may not have been 3 here, she said one of the first things she did, 4 though, when she came on with Lilly was to review 5 the Lilly clinical investigators brochures, so 6 some brochures must have been in existence. 7 Q. Paul just told me when I 8 wasn't here yesterday that you testified that 9 part of your responsibility when you first came 10 on board with the Fluoxetine project, not as 11 project leader, but generally related to the 12 project, it was your responsibility to review 13 existing clinical investigation manuals. Is that 14 true? 15 A. Right. That was a clinical 16 investigation brochure that talked about the drug 17 Fluoxetine. 18 Q. Okay. 19 A. It was not a policy manual. 20 Q. Okay. Did the investigation 21 brochure contain any policies that Lilly had in 22 place as far as how to run clinical trials, the 23 kind of data gathering that needed to be done, 24 things of that nature? Page 338 1 A. No, it was a reporting on the 2 drug and what we knew about the drug to that 3 point in time. 4 Q. So it's your testimony that at 5 least to the best of your recollection at this 6 period of time, meaning June of 1984, the policy 7 manuals related to the gathering of information, 8 things of that nature, would have been in the 9 works, so to speak? 10 A. In the works or could have 11 been shortly, I can't identify a time. 12 Q. Okay. To the best of your 13 recollection, up to June of 1984, had clinical 14 trials been performed on Fluoxetine, either by 15 Lilly or on behalf of Lilly? 16 MR. MYERS: Let me object. Nancy, she 17 answered that at length over the course of the 18 last day and a half. 19 Q. Yes or no. 20 A. Yes, clinical trials have been 21 conducted on Fluoxetine. 22 Q. Had clinical trials been 23 conducted on Fluoxetine prior to the time when 24 the policy manual portions of the clinical Page 339 1 manuals -- policies, as far as data collection, 2 et cetera, that we've just been talking about, 3 had clinical trials been performed prior to those 4 manuals being finalized? 5 A. Yes. 6 Q. What was done in the interim 7 before those manuals were finalized to inform 8 clinical investigators as to how they should 9 proceed as far as data collection, running the 10 clinical trials, you know? 11 A. The protocol, every study had 12 a protocol, and that was the guideline on how to 13 conduct the trial. 14 Q. Okay. Was everything 15 regarding the conducting of the clinical trials 16 set forth in the protocol? 17 A. What do you mean was 18 everything set forth in the protocol? 19 Q. Well, I mean were definitions 20 of terms set out in the protocols? 21 MR. MYERS: When you say terms, any 22 terms? 23 MS. ZETTLER: Any terms. 24 A. I don't know how to respond to Page 340 1 that. 2 Q. For instance, concomitant 3 medications, is that something that was set out 4 in the protocol's definition? 5 A. I know it talked about the 6 collection of concomitant medications. 7 Q. Would it set out, for 8 instance, an exclusion criteria on medications 9 that should not be given concomitantly? 10 A. Yes. 11 Q. Would it talk about what a -- 12 what the term concomitant medication was 13 specifically, in other words would it define the 14 term? 15 A. Within the protocol? 16 Q. Right. 17 A. That may not have been within 18 the protocol, that may have been on the actual 19 case report form, instructions on how to collect 20 this data. 21 Q. Okay. To your knowledge were 22 there separate manuals for the U.S. clinical 23 trials as opposed to the outside the United 24 States clinical trials? Page 341 1 MR. MYERS: When you say manuals, what 2 do you mean? 3 Q. Clinical investigation 4 manuals. 5 A. You mean the clinical 6 investigational brochure? 7 Q. Right. 8 A. No, I think there was one. 9 Q. So the German affiliates, if 10 they were working on Fluoxetine trials, would 11 have been provided with a copy of the same 12 clinical investigation brochure that was used 13 here in the United States? 14 A. That would be my assumption. 15 Q. To the best of your 16 recollection, has there ever been an issue at 17 Lilly as to whether or not Fluoxetine was a 18 stimulating, activating antidepressant prior to 19 1990? 20 A. This Exhibit 4 indicates that 21 that was a question from the BGA. 22 Q. Other than the question from 23 the BGA, to the best of your recollection was 24 that ever raised as an issue prior to 1990 by any Page 342 1 other source? 2 A. Could you repeat the word she 3 wants me to respond to? 4 Q. Whether or not -- I'll just 5 rephrase it. Besides the question raised by the 6 BGA as reflected in Exhibit 4, okay? 7 A. Okay. 8 Q. To the best of your 9 recollection, was there ever an issue regarding 10 whether or not Fluoxetine was a stimulating 11 and/or activating drug as an antidepressant prior 12 to 1990? 13 A. We continuously reviewed the 14 adverse event profiles as we gathered the data, 15 and the data base continued to grow, and so I 16 mean we looked across it for a lot of different 17 things, and nervousness was an adverse event that 18 did occur. I can't equate that to an activating 19 and stimulating drug. We looked at the groups of 20 adverse events, we knew that it would cause 21 nervousness in some people. 22 Q. How about anxiety, do you 23 recall seeing adverse events related to anxiety? 24 A. I mean the term anxiety did Page 343 1 appear as an adverse event. 2 Q. How about agitation, do you 3 recall seeing the event term agitation related to 4 Fluoxetine? 5 A. Yes. 6 MR. MYERS: Wait a minute. When you 7 say related, you mean occurring in a trial where 8 Fluoxetine was being tested because they're 9 blinded? 10 A. Yes, they were blinded, and we 11 did see that event term appear in our data base. 12 Q. When you say the data base, 13 you mean the clinical trial data base? 14 A. Clinical trial data base, yes, 15 I do. 16 Q. When were the studies 17 unblinded with regards to adverse events? 18 A. At the completion of the 19 studies, unless there was a very serious event 20 and we needed to unblind it, but that was seldom. 21 The first discussion with the physician was will 22 it impact on how you're going to care for the 23 patient. 24 Q. Whether or not -- what drug Page 344 1 they're on? 2 A. Yes. 3 Q. So, for instance, if a patient 4 overdosed on a study drug, a medication given to 5 them throughout the study, whether or not it was 6 a placebo or comparitor of Fluoxetine, you may or 7 may not want to know which drug the person 8 overdosed on so you would know how to treat them? 9 A. For that one, I would say you 10 need to know that to be able to treat the 11 patient. 12 Q. But if a person came down with 13 a serious rash, you may not need to know. 14 A. May or may not. Again, those 15 were physician to physician discussions. 16 Q. Okay. Other than needing to 17 break the blind in response to an adverse event 18 that was serious, considered serious, it's your 19 testimony that the blind would not be broken then 20 until the end of the study; correct? I mean 21 generally. 22 A. Generally, yes. 23 Q. With regards to serious 24 adverse events that occurred during a study, Page 345 1 unless it was essential to know what medication 2 that patient was on, like, for instance, in our 3 overdose example, is it your testimony that the 4 blind may or may not have been broken until the 5 end of the study? 6 A. To the investigator. 7 Q. Okay. Any serious adverse 8 event, the blind would be broken at Lilly? 9 A. If it was -- if it deemed that 10 a 1639 needed to be submitted. Initially we were 11 not breaking the blind because we did not want it 12 to be unblinded. The FDA requested they wanted 13 to know what study drug the patient was on. But 14 the investigator would not necessarily know. 15 Q. Do you recall when the FDA 16 requested that the blind be broken on 1639 17 reports? 18 A. A specific date? 19 Q. Generally. 20 A. In the '80s, I'm sorry. 21 Q. Was it before the FDA approved 22 the drug for marketing? 23 A. Probably. 24 Q. Do you know why they requested Page 346 1 that the blind be broken on 1639 reports? 2 A. So they would know as opposed 3 to just getting a lot of blind data that wasn't 4 very meaningful. 5 Q. Do you recall that as a 6 specific request with Fluoxetine or was that 7 something that was requested across the board on 8 all drugs? 9 A. That was a general request for 10 all drugs. 11 Q. Do you recall if that request 12 was specific to Lilly or if that was a general 13 request to all drug companies? 14 A. I don't know the answer to 15 that. 16 Q. Earlier you testified, and if 17 I'm stating this wrong, let me know because I 18 don't recall exactly how you said it, but that 19 the German regulations had changed at some point 20 and Doctor Weber asked for additional information 21 on adverse events that were reported; is that 22 correct? 23 A. Yes. 24 Q. Do you recall what additional Page 347 1 information Doctor Weber needed to comply with 2 the changed German regulations? 3 A. They were interested in all 4 adverse events, whether they were serious or 5 nonserious, as I recall. 6 Q. Is the serious definition used 7 by Germany the same as the serious definition 8 used by the FDA? 9 A. I have never seen them 10 side-by-side, so I can't say with surety. 11 Q. Do you recall when that 12 request was made? 13 A. That's probably been within 14 the last eighteen to twenty-four months. 15 Q. When they say they want all 16 serious and nonserious adverse events, does that 17 include adverse events that occur in clinical 18 trials, to your knowledge, or is that spontaneous 19 adverse events alone? 20 A. I don't know the delineation 21 on that request. 22 Q. Is it your recollection that 23 at some point in time the BGA rejected Lilly's 24 application for marketing of Fluoxetine in Page 348 1 Germany? 2 MR. MYERS: She answered that 3 yesterday. 4 A. Again, this Exhibit 4, they 5 had a lot of questions, and we responded to 6 those. The drug is marketed in Germany. 7 Q. But that's -- I know it's 8 marketed in Germany today. Let me ask it this 9 way: Do you recall when the BGA finally approved 10 the sale of Fluoxetine in Germany? 11 A. No. 12 Q. Was it prior to your leaving 13 the Fluoxetine group? 14 A. No. 15 Q. It was after you left the 16 Fluoxetine group that they approved it? 17 A. Yes. 18 Q. Other than knowing that it has 19 been approved since the Fall of 1988, do you 20 recall at any time the BGA rejecting Lilly's 21 application for marketing of Prozac in Germany? 22 A. Not that I'm aware of. 23 Q. Are you aware of any country 24 rejecting the application for marketing of Prozac Page 349 1 in that country? 2 A. Flat out rejecting it? 3 Q. Yes. 4 A. Not that I recall. 5 Q. Do you recall Lilly 6 withdrawing an application or a proposal that the 7 drug Fluoxetine be marketed in any particular 8 country? 9 A. Again, those are discussions 10 that are well above where I am in the 11 organization. I really don't know. 12 Q. Okay. Do you recall reporting 13 foreign regulatory actions to the FDA at any 14 point in time? 15 A. That was a request. 16 Q. Request from whom, the FDA? 17 A. I think that was from the FDA 18 before we had probably -- before we had the 19 approvable letter even, or between approvable and 20 approval. 21 Q. Do you recall what information 22 was provided to the FDA on foreign regulatory 23 activities at that time? 24 A. There was a response that was Page 350 1 prepared. I didn't prepare it, and I don't 2 recall the specifics of it. 3 (A SHORT RECESS WAS TAKEN.) 4 Q. Ms. Ashbrook, I understand, 5 again, I wasn't here at this portion yesterday, 6 but I want to ask you one quick follow-up because 7 I want to make sure you understand what I'm 8 asking you, so I'll repeat a couple of short 9 questions. I understand that your ex-husband 10 works for Lilly; is that correct? 11 A. Yes. 12 Q. And at this time he's a patent 13 attorney for Lilly? 14 A. Yes. 15 Q. When did he become a patent 16 attorney for Lilly? 17 MR. MYERS: She told Paul this 18 yesterday, Nancy, they went through all this. 19 It's not even follow-up. 20 MS. ZETTLER: There was some 21 confusion, Larry. 22 MR. MYERS: Let's get to the 23 confusion, please. 24 MS. ZETTLER: I want to know when he Page 351 1 became a patent attorney for Lilly, that's all I 2 want to know. 3 MR. MYERS: Okay. 4 Q. You can give me a year. 5 A. Well, after he passed the 6 patent bar, he graduated from law school in '79. 7 And he took the bar, so whenever he got the 8 results from the bar. 9 Q. So early '80s? 10 A. Right. He was a patent agent 11 as he was going to law school. 12 Q. And then when he went into the 13 patent area, he no longer worked in the chemistry 14 department? 15 A. That's correct. 16 MS. ZETTLER: That's all I wanted to 17 know. 18 (DISCUSSION OFF THE RECORD.) 19 Q. Have you ever heard of Doctor 20 Ivan Miller? 21 A. No. 22 Q. Have you heard of a clinical 23 trial surveillance study being done on the 24 validation of a suicidality scale? Page 352 1 A. I didn't hear all your words. 2 Q. Have you heard of a validation 3 study or clinical trial being performed on behalf 4 of Lilly to validate a suicidality scale, 5 suicidal ideation scale? 6 A. I'm not aware of that. 7 Q. Have you heard of a study 8 S002? 9 A. Study S002? 10 Q. Right. I think it's 11 B1Y-MC-S002. 12 A. No. 13 Q. Have you heard of a 14 rechallenge protocol or a study that was done or 15 contemplated at Lilly at any time on the issue of 16 suicidality? 17 A. No. 18 (PLAINTIFFS' EXHIBIT NO. 9 WAS 19 MARKED FOR IDENTIFICATION AND 20 RECEIVED IN EVIDENCE.) 21 Q. Have you had a chance to 22 review Exhibit 9? 23 A. Yes, I have. 24 Q. Do you recognize this exhibit? Page 353 1 A. It's a report that came out 2 with an update of the trials. 3 Q. Okay. Towards the bottom 4 middle of the page, do you see a reference to 5 S002 suicide scale? 6 A. I see that. 7 Q. Does that refresh your 8 recollection as to whether or not such a study 9 was performed by Lilly or on behalf of Lilly? 10 A. No, it doesn't. 11 MR. SMITH: Nancy, tell her that 12 you're not trying to trick her by marking a bunch 13 of stuff out, that you didn't do that. 14 MR. MYERS: Don't pay any attention to 15 that, he's just causing trouble down there. 16 Q. But, I mean, he does make a 17 good point, Ms. Ashbrook, I would like you to 18 know that anything that was blacked out on these 19 sheets was not blacked out by us, that was 20 blacked out by your employer. 21 MR. MYERS: You can believe that. 22 Don't concern yourself with it, but she's 23 correct. 24 THE WITNESS: I'm not concerned. Page 354 1 Q. Yesterday you and Paul talked 2 at length about, and we talked a little bit about 3 it today, whether or not you were aware of the 4 issue of suicidality and the use of Fluoxetine 5 prior to 1990, other than the BGA issues that 6 were raised, okay. Is that an accurate 7 statement? 8 A. Repeat it again, please. 9 Q. Sure. My understanding of 10 your testimony is that with regards to the issue 11 of suicidality and the use of Fluoxetine as it 12 occurred, whether or not it occurred prior to 13 1990, okay, it's been your testimony that other 14 than the BGA issues that we've talked about 15 already, you were not aware of that issue being 16 raised; correct, suicidality and the use of 17 Fluoxetine? 18 A. That's correct. 19 MR. MYERS: Wait a minute. Before you 20 answer it, let me object to the form because I 21 don't know that the BGA inquiry and that are the 22 same thing, I don't know that that's been 23 established. 24 MS. ZETTLER: You mean the BGA inquiry Page 355 1 and the issue of suicidality and Fluoxetine? 2 MR. MYERS: Right, that they're one 3 and the same. 4 MS. ZETTLER: I think Exhibit 4 speaks 5 for itself, and so does Exhibit 5. 6 MR. MYERS: Right. 7 Q. Is that your understanding, 8 Ms. Ashbrook, that other than the issues that 9 were raised by the BGA, you were not aware of an 10 issue with regards to Fluoxetine and suicidality 11 prior to 1990? 12 MR. MYERS: Same objection. Answer it 13 if you can. 14 A. No, I was not aware. 15 Q. Okay. And as far as agitation 16 and the use of Fluoxetine goes, other than the 17 adverse event terms that you've seen, and the 18 issues raised by the BGA, is it also your 19 testimony that you were not aware of that issue 20 specific to the use of Fluoxetine prior to 1990? 21 MR. MYERS: When you say that issue, 22 do you mean as a treatment or as an event? 23 MS. ZETTLER: As an event, outcome. 24 Q. Other than what was raised by Page 356 1 the BGA as to whether or not Fluoxetine is a 2 stimulant, right? 3 A. Right. 4 Q. And the adverse event terms 5 that you had seen periodically throughout your 6 career on Fluoxetine -- 7 A. That's correct. 8 Q. -- were you aware of agitation 9 related to the use of Fluoxetine as an issue at 10 any time before 1990? 11 MR. MYERS: Other than what she's 12 already said? 13 MS. ZETTLER: Right. 14 A. Other than from the BGA 15 document. 16 Q. Okay. Prior to 1990, were you 17 ever aware of the issue of suicide, suicidality 18 in agitated depressed patients being treated with 19 Fluoxetine, specifically? 20 A. No. 21 Q. Okay. Prior to 1990, were you 22 aware of the issue of agitation leading to 23 suicidality in depressed patients treated with 24 Fluoxetine? Page 357 1 A. Would you repeat that? 2 Q. Agitation leading to 3 suicidality in patients being treated with 4 Fluoxetine. 5 A. Not a link, no. 6 Q. Were you aware of that as an 7 issue, whether or not there was a link between 8 agitation and the use of Fluoxetine, that would 9 result in suicidality? 10 A. I was aware that people on 11 Fluoxetine reported the adverse event, the 12 nervousness, some of the other ones that you had 13 quoted. 14 Q. Anxiety, agitation? 15 A. That's what I was aware of. 16 Q. Were you aware that there was 17 an issue as to whether or not agitation produced 18 suicidality in Fluoxetine patients prior to 1990? 19 A. Other than, like I said, the 20 inquiry from the BGA, when we looked at the data 21 base. 22 (PLAINTIFFS' EXHIBIT NO. 10 WAS 23 MARKED FOR IDENTIFICATION AND 24 RECEIVED IN EVIDENCE.) Page 358 1 Q. Have you had a chance to 2 review Exhibit 10? 3 A. Yes. 4 Q. Do you recognize that exhibit, 5 Ms. Ashbrook? 6 A. I probably have seen this, I 7 mean after I reviewed it, it was what it says, 8 that Fluoxetine international B-Form meeting, and 9 that's the topics to cover at that meeting. 10 Q. Okay. Did you attend this 11 meeting? 12 A. I was listed as a major 13 addressee. 14 Q. To the exhibit? 15 A. To the exhibit. 16 Q. Okay. 17 A. I would assume I attended the 18 meeting, I don't recall for sure. 19 Q. On the second page of the 20 exhibit at the top, it says Fluoxetine 21 international B-Form meeting, December 4th, 1984, 22 topics for discussion. Do you see that? 23 A. Yes. 24 Q. And under number three, Page 359 1 organization of clinical efficacy section, under 2 decisions regarding integration and presentation 3 of data, it says BGA analysis; correct, about 4 halfway down the list? 5 A. Yes, it does. 6 Q. Would this be the BGA analysis 7 that was done in response to questions by the BGA 8 that we talked about earlier? 9 A. Yes, it's in the same time 10 frame. 11 Q. Under number four, 12 organization of clinical safety section, 13 decisions regarding integration and presentation 14 of data, again it lists BGA analysis; correct? 15 A. Yes. 16 Q. Would this again be the BGA 17 analysis that was done in response to questions 18 we talked about earlier? 19 A. Right, it was the analysis we 20 were working on to respond to those inquiries. 21 Q. To your knowledge, were those 22 safety and efficacy BGA analyses in fact 23 incorporated into the international B-Form? 24 A. I don't recall. Page 360 1 Q. Do you recall ever seeing that 2 information incorporated into the international 3 B-Form after this date, December of '84? 4 A. At this point, I can't 5 remember. 6 Q. If you could go back to the 7 sixth page of the exhibit, which is Pz 1062 1178. 8 Do you see that? 9 A. Uh-huh. 10 Q. You have to say yes or no. 11 A. Yes. 12 Q. At the top of the page it says 13 Fluoxetine issues, 11-13-84; correct? 14 A. Yes. 15 Q. Under C, analysis needed, 16 priorty one. Number five, agitation suicide, 17 position statement in progress. Do you see that? 18 A. Yes. 19 Q. Do you know what that refers 20 to? 21 A. The response -- I think at 22 that time we were developing responses to the 23 BGA. It all centered around the request for 24 information for the BGA. Page 361 1 Q. When you say it all centered 2 around, do you mean the development of the 3 international B-Form that's being discussed in 4 this exhibit? 5 A. No, these particular topics 6 that you referred to. 7 Q. To your knowledge was the 8 specific issue of agitation suicide that was 9 being analyzed in response to the BGA ever raised 10 by Lilly with the FDA, in other words did Lilly 11 ever go to the FDA and say we're doing this 12 analysis on agitation suicide in response to 13 questions by the BGA? 14 A. I have no knowledge of that. 15 Q. If you could look at the 16 second to the last page of the exhibit, which is 17 marked Pz 1062 1182. Do you see that? 18 A. Uh-huh. 19 Q. You have to say yes or no. 20 A. Yes. 21 Q. At the top it says Fluoxetine 22 B-Form clinical safety chapter, query sheet, 23 November 27th, 1984. Do you see that? 24 A. Yes. Page 362 1 Q. Under that it says decisions 2 needed to continue preparing the B-Form; correct? 3 A. Yes. 4 Q. Under number one it says 5 serious adverse experiences. And under that it 6 says serious adverse experiences are presented in 7 the overview: An, quote, occasional, unquote, 8 bracket, no number given in NDA-Highlights, page 9 eighty, close bracket, patient became psychotic 10 or was described as having hallucinations; one 11 case of very severe skin rash; one case of 12 erythemia multiforme; two patients and one 13 volunteer who had episodes possibly representing 14 convulsive seizures. Correct? 15 A. That's what it says. 16 Q. Do you know what it means by, 17 quote, occasional, unquote? 18 A. With respect to an numeric 19 interpretation? 20 Q. Yes. 21 A. Not, no, I can't give an 22 numeric number to that. 23 Q. When you say with respect to 24 an American interpretation, who put together this Page 363 1 outline, do you know? 2 A. The message was sent by Jan 3 Potvin. 4 Q. Okay. 5 A. And she was a writer that was 6 working with the physician to pull this together. 7 Q. Okay. 8 A. And I imagine these were her 9 questions to be able to complete the -- they've 10 got international B-Form, and back in here on Pz 11 1062 1182, it just talks about a Fluoxetine 12 B-Form. I can't tell at this point, was it all 13 the same document. 14 Q. Okay. Why is it that you 15 think that there may be an outside the United 16 States or a non-English interpretation of 17 occasional for that page, the second to the last 18 page, under number one? 19 MR. MYERS: Non-English? 20 MS. ZETTLER: Right. 21 MR. MYERS: She said numeric. 22 Q. You said numeric? 23 A. I said numeric. 24 Q. I'm sorry, I misunderstood Page 364 1 you. So it's a numeric interpretation, is that 2 what? 3 A. When I would look at that, 4 that's what I would say. But I don't know what 5 is the number. 6 Q. Would that be a percentagewise 7 determination, to your knowledge? 8 A. I don't know. 9 Q. Is what's considered 10 occasional in the context of Exhibit 10, that 11 second to last page, under number one, serious 12 adverse experiences, something that is determined 13 by the FDA, to your knowledge? 14 A. The term occasional? 15 Q. What would be considered 16 occasional within the realm of the clinical 17 trials for the adverse events that were reported? 18 A. I don't understand your 19 question. 20 Q. I'm trying to find out if 21 whether or not the occurrence of an adverse event 22 is deemed occasional is something that is defined -- 23 is occasional something that is defined by the 24 FDA, such as the regulations that define serious. Page 365 1 MR. MYERS: As used here? 2 MR. SMITH: Right. 3 A. As in occasional being a 4 definition that's given by the FDA? 5 Q. Right. 6 A. Not that I am aware of. 7 (PLAINTIFFS' EXHIBIT NO. 11 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Have you had a chance to 11 review Exhibit 11? 12 A. Yes, I have. 13 Q. Do you recognize this exhibit? 14 A. No. 15 Q. It looks like a two-page 16 letter signed by John Heiligenstein dated March 17 11, 1987; correct? 18 A. That's what it says. 19 Q. And while it doesn't seem to 20 have an addressee on the letter, it appears to be 21 a letter to an investigation site, does it not? 22 A. That's what it appears to be. 23 Q. You're blanked carbon copied 24 at the top of the right-hand corner of the first Page 366 1 page. 2 A. Yes. 3 Q. It appears to be a Tomoxetine 4 and Fluoxetine audit report which is at least the 5 basis of the first page of the discussion; 6 correct, the letter? 7 A. That's what it appears to be. 8 Q. On the second page of the 9 letter, second to the last paragraph, Doctor 10 Heiligenstein refers to a separate letter dated 11 January 29th, 1987. It appears to be to Lilly 12 regarding Lilly's concern about the need to 13 report overdoses and suicide gestures or 14 attempts. Do you see that? 15 A. I see that. 16 Q. Do you recall whether or not 17 that was a concern of Lilly's back in January of 18 1987, that suicide attempts, overdoses and 19 suicide gestures be reported to Lilly within 20 twenty-four hours? 21 A. Again, we considered those 22 serious adverse events, and from the initiation 23 from the questions from the BGA, where they were 24 asking us those kind of questions. Page 367 1 Q. So as of 1984, when the BGA 2 raised the issue of suicide attempts, 3 suicidality, that became an issue that was of 4 concern to Lilly? 5 A. Again, serious adverse events 6 needed to be -- that was stated in protocols to 7 call us. What was said to each specific 8 investigator, I wasn't at those meetings. 9 Q. Was there a problem with the 10 Fluoxetine and Tomoxetine audit, to the best of 11 your recollection, that raised the issue of 12 overdoses and suicidal attempts or gestures 13 specifically? 14 A. I don't remember this audit. 15 Q. Seriousness of an adverse 16 events is an FDA definition; correct? 17 A. Yes. 18 Q. And it's really outcome 19 specific, is it not? 20 A. What do you mean outcome 21 specific? 22 Q. Whether or not an adverse 23 event is considered serious under the FDA 24 regulations is determined by the event's outcome? Page 368 1 MR. MYERS: I object to the form, 2 because I think if you look at the reg, I think 3 you're wrong, just flat wrong. If you know, tell 4 her. I can think of one where you're absolutely 5 wrong. 6 MR. SMITH: Is there a difference 7 between wrong, flat wrong and absolutely wrong? 8 MR. MYERS: No, it's like 9 instantaneous recall. 10 MR. SMITH: Are there regulations in 11 connection with that, and definitions of that? 12 MR. MYERS: Not that I'm aware of. 13 I'll consult the CFR. 14 MR. SMITH: Why don't we proceed. 15 MR. MYERS: Sure. Answer her if you 16 know. She wants to know if they're outcome 17 dependent, I think. 18 A. I know they collect outcomes. 19 Q. Let me ask you this: What 20 makes an adverse event serious under the FDA 21 regulations? 22 A. There are some that are 23 specified as serious if they occur. 24 Q. Such as, give me an example. Page 369 1 A. Congenital anomalies, any 2 adverse event that causes hospitalization. 3 Q. Death? 4 A. Yes, death. 5 MR. SMITH: Cancer. 6 Q. Cancer? 7 A. Yes. 8 Q. Any others? 9 A. Overdose was in there at one 10 point, I don't know if it's still in there or 11 not. 12 Q. In the FDA regulations or in 13 Lilly's policy? 14 A. I think it was in -- I would 15 have to go back and look when the new regulations 16 came out with those definitions. 17 Q. Okay. Besides adverse event 18 resulting in hospitalization, death, overdose, 19 congenital anomaly and cancer, what else under 20 the FDA regs, to your knowledge, makes an adverse 21 event serious? 22 A. How severe the adverse event 23 was. 24 Q. Okay. So you could have an Page 370 1 adverse event that does not result in 2 hospitalization, death, overdose, cancer, 3 congenital anomaly, and whatever else is set out 4 specifically that is outcome related, that could 5 still be considered serious depending on the 6 severity? 7 A. Yes. 8 Q. Can you give me an example? 9 A. It goes hand in hand with 10 expectedness and unexpected, and it's not in and 11 of and by itself. 12 Q. If you had a suicide attempt 13 where somebody took ten aspirins, and basically 14 was fine, did not have to be hospitalized, didn't 15 cause a congenital anomaly or cancer or result in 16 death, would that be considered serious? 17 MR. MYERS: I object to the form, that 18 may well be a medical question. If you know, 19 tell her. 20 Q. You were the head of the DEU 21 for a period of time, were you not? 22 A. I was the administrative 23 manager of the drug epidemiology unit. 24 Q. And as administrative manager Page 371 1 of the drug epidemiology unit, do you have any 2 responsibility to make sure that people working 3 under you were trained to do their job? 4 A. Yes, there was a training 5 program for them, I did not provide the training 6 program. 7 Q. Did you feel that to a certain 8 extent you needed to be familiar with FDA 9 regulations regarding reporting of adverse events 10 to be able to perform your administrative duties? 11 A. I needed to have general 12 knowledge of them, I didn't need to know them 13 down to detail. The folks in the unit and the 14 department head needed to know those because they 15 were working with the information day to day. 16 Q. What about -- where did you 17 get your knowledge as to the federal regulations 18 related to the definition of serious adverse 19 events? 20 A. From our policies and 21 procedures manual. 22 Q. When did you first read that, 23 was that part of your job as department head of 24 DEU? Page 372 1 A. As the policy and procedure 2 manuals came out, if you were in medical, you 3 read them. 4 Q. Tell me how the serious 5 expected or serious unexpected portions of the 6 FDA regs worked together. You said that they go 7 hand in hand, how do they go hand in hand? 8 A. You're asking if serious was 9 only outcome based? 10 Q. Okay. 11 A. Again, from the reporting 12 criteria, they're most interested in those that 13 are serious and unexpected. 14 Q. When you say they, you mean 15 the FDA? 16 A. The FDA had to report to them 17 serious and expected. And again, it gets into 18 the timing with which you need to report that to 19 the FDA. 20 Q. Okay. 21 A. It wasn't as critical to get 22 serious expected in as it was the serious 23 unexpected from the timing standpoint. 24 Q. So if I understand your Page 373 1 testimony correctly, serious unexpected adverse 2 events would have to be reported in a much 3 shorter time period than serious expected adverse 4 events? 5 A. I think that's true. 6 Q. What determines whether or not 7 an adverse event is expected or unexpected? 8 A. Expected event would be those 9 that had been seen before in the clinical trials. 10 Q. Would it have to be seen more 11 than once in a clinical trial to become expected? 12 A. I can't answer that. 13 Q. Who made the determination as 14 to whether or not an adverse event was expected 15 or unexpected at Lilly? 16 A. As you continue to gather data 17 from the trials and you saw that information come 18 in, if it occurred while they were on a trial and 19 we continued to collect those so the data base 20 would grow, we would monitor that. And, so, if 21 you had, for example, a report of headache, and 22 it occurred several times, you would say during 23 clinical trials with Fluoxetine, headache does 24 occur. Page 374 1 Q. How about violent-aggressive 2 behavior, was that considered an expected adverse 3 event while you were working in the DEU? 4 A. With respect to? 5 Q. The use of Fluoxetine. 6 A. I don't know the specific 7 adverse events at this point in the label, on 8 Fluoxetine, for expected or unexpected. 9 Q. What does the label have to do 10 with whether or not an adverse event is expected 11 or unexpected? 12 A. You continue to monitor, and 13 the label has been changed, the clinical 14 investigators brochure has been changed, I don't 15 know what they state now. 16 Q. Okay. But my question is: 17 What does the label and the brochure have to do 18 with whether or not an adverse event is 19 considered expected or unexpected at Eli Lilly? 20 A. I'm sorry. 21 Q. That's okay. 22 A. The clinical investigational 23 brochures still go out to investigators 24 conducting our studies, they get a list of Page 375 1 adverse events that have occurred on our trials, 2 so they are aware of those. Those would be 3 expected. 4 Q. So they're given a list by 5 Lilly of what is to be considered or what is 6 considered by Lilly to be an expected adverse 7 event? 8 A. Based on what's in our data 9 base. 10 Q. How about the package insert, 11 how does that work into this expected, unexpected 12 determination? 13 A. There's been -- you know, it 14 has been changed based upon additional data 15 learned about the product over time. 16 Q. That still doesn't answer my 17 question. How does that work into the 18 determination as to whether or not an event is 19 expected or unexpected? 20 MR. MYERS: What she wants to know, I 21 think -- you told her you use the clinical 22 investigator brochure, and what is listed in 23 there, to make a determination. Why at some 24 point in time are you looking at the package Page 376 1 insert to make that kind of determination. 2 A. Okay. It's not either or. 3 Since the product has been marketed, that 4 information is available. 5 Q. So in other words, you look at 6 the package insert to see if an adverse event is 7 listed in the package insert, and if it's listed 8 in the package insert, it's considered expected? 9 A. I think so. 10 Q. A couple of seconds ago you 11 stated that there was a list of adverse events 12 that is provided to the investigators in the 13 clinical investigation brochure; correct? 14 A. Yes. 15 Q. Are there numbers listed as to 16 how many times each individual adverse event has 17 occurred within Lilly trials up to that date? 18 MR. MYERS: In the brochure? 19 Q. Right, to the date of the 20 brochure. 21 A. I don't know how it's 22 currently done. When I had that -- you know, was 23 in the plans area, and we did that, yes, we had 24 the number of occurrences. Page 377 1 Q. When was the last time that 2 you saw one of those brochures? 3 MR. MYERS: When you say one of those, 4 one of those that has -- 5 MS. ZETTLER: Clinical investigator 6 manual brochures -- clinical investigation 7 brochures that had an adverse event listing in 8 it. 9 A. For Fluoxetine? 10 Q. Right. 11 A. It was probably one of the 12 last ones that was done. 13 Q. Do you want to refer to an 14 exhibit? 15 A. Well, there was the exhibit 16 that we -- what exhibit was it, the one from Jan 17 Potvin that we were having our discussion. 18 Q. Exhibit 10. 19 A. That one -- I would know that 20 whenever the one came out that we were working on 21 in June 18, 1985, I would have seen that one. 22 Q. Who at Lilly decided what 23 adverse event should be included in the package 24 insert? Page 378 1 A. All adverse events that were 2 reported from our clinical trials were included 3 in the package insert. 4 Q. Every single adverse event 5 that ever occurred on any clinical trial is 6 included in the package insert? 7 A. In the listing below the table 8 was the placebo controlled studies, and that was 9 a table. And then below that, we listed others 10 that included all Fluoxetine patients that had 11 had at least one dose of Fluoxetine. 12 Q. Who made the decision what to 13 include in that section? 14 A. I don't know that it was any 15 one person's decision. 16 Q. What group was responsible for 17 putting together the package insert? 18 A. The physicians and regulatory. 19 I was part of it, I wasn't making the decisions, 20 I saw that it got carried out, and what they 21 wanted was done. 22 Q. Did you review lists of 23 adverse event terms that were included in the 24 package insert? Page 379 1 A. Yes. 2 Q. When was the last time that 3 you worked on a package insert on Fluoxetine? 4 A. I know for sure I worked on 5 one right before approval. 6 Q. In 1987? 7 A. 1987. 8 Q. So was that the initial 9 package insert that was used once the drug was 10 marketed? 11 A. With whatever modifications 12 that the FDA had made. The FDA had the final say 13 in what your package literature does say. 14 Q. In the form of the package 15 insert that you reviewed, do you recall suicide 16 attempt being listed as an adverse event? 17 A. If it had occurred in the 18 clinical trial, it was listed. 19 Q. To your knowledge, prior to 20 1987, had anybody attempted suicide during a 21 clinical trial? 22 A. To my knowledge, what I 23 recall, was the one successful suicide of the 24 patient. Page 380 1 Q. So to your knowledge should 2 suicide attempt, based on that one suicide 3 attempt that you were aware of, should that have 4 been included in the package insert? 5 A. That would have been listed as 6 a suicide. If suicide attempt was in there, 7 there must have been other data that would have 8 stated suicide attempt. 9 Q. If suicide attempt was listed 10 in the package insert? 11 A. Yes. 12 Q. And what if it was not listed 13 in the package insert, why would it not be listed 14 in the package insert? 15 A. We didn't have any in our data 16 base. 17 Q. Have you ever seen a situation 18 where there was information on an adverse event 19 in the data base that was not listed in the 20 package insert? 21 A. Would you repeat that? 22 Q. Are you aware of any instance 23 where there's information related to an adverse 24 event that occurred during a clinical trial that Page 381 1 was not mentioned in the package insert? 2 A. Not to my knowledge. 3 Q. Would adverse events that 4 occurred during clinical trials be listed in the 5 package insert regardless of whether or not a 6 causal connection between Fluoxetine and that 7 adverse event had been established? 8 A. Yes. 9 Q. How about hostility, do you 10 recall at that time prior to FDA approval whether 11 or not hostility appeared as an adverse event in 12 the package insert? 13 A. I don't recall. 14 Q. How about violent-aggressive 15 behavior? 16 A. I don't recall. 17 Q. How about depression, is that 18 listed as an adverse event in the package insert 19 in 1987 prior to approval? 20 A. It was in our data base. 21 Q. So, then, it's your testimony 22 that it would have been listed in the package 23 insert? 24 A. It would have been listed in Page 382 1 our proposed insert. 2 Q. Okay. To your knowledge, did 3 the FDA take out any adverse event terms that 4 were listed by Lilly in the package insert? 5 A. The FDA had the final say in 6 it. I know they moved some things around and 7 changed some things, I don't recall what it was. 8 Q. You don't have any specific 9 recollection of them saying we don't want this 10 event term listed in the package insert or 11 anything of that nature? 12 A. It talked about things that 13 were in no way, shape or form could have been 14 related. I know you're going to ask me for an 15 example. 16 MR. MYERS: Pregnancy. 17 MS. ZETTLER: I don't know, some 18 people might say suffering from depression can 19 cause pregnancy. 20 THE WITNESS: I can't respond to that. 21 MR. SMITH: I object to defense 22 counsel continuing to interject. 23 A. Surgical procedure might be 24 one. Page 383 1 Q. Surgical procedure could be 2 one? 3 A. Could have been one. 4 Q. Isn't it true that at one 5 point the DEU or the physicians at Lilly 6 considered listing accidental injuries under the 7 event term of surgical procedure in Fluoxetine 8 studies? 9 MR. MYERS: I object to the form. 10 That assumes something I don't think is a fact, 11 but if you know, tell her if they were doing 12 that. 13 A. I don't recall that kind of a 14 mapping of terms. 15 Q. What synonyms fell under the 16 event term depression? 17 A. I'm not going to be able to 18 remember. 19 Q. How about suicidal ideation, 20 did that ever map to depression? 21 A. I would have to see a 22 dictionary, I really can't tell you. 23 (PLAINTIFFS' EXHIBIT NO. 12 WAS 24 MARKED FOR IDENTIFICATION AND Page 384 1 RECEIVED IN EVIDENCE.) 2 Q. Have you had a chance to 3 review Exhibit 12? 4 A. Yes. 5 Q. Whose handwriting is that on 6 the first page of Exhibit 12? 7 A. Mine. 8 Q. This says form 1639; correct? 9 A. Yes. 10 Q. FDA 1639 form. And those are 11 forms that are used to report adverse events to 12 the FDA; correct? 13 A. Yes. 14 Q. At least it's one way of 15 reporting adverse events to the FDA, right? 16 A. Yes. 17 Q. And this is dated at the 18 bottom left-hand corner 3-24-86; correct? 19 A. Yes. 20 Q. Does this -- first of all, 21 this form is generated by the DEU at Lilly, 22 right, the completed form? 23 A. At this point, yes. 24 Q. Is it generated by another Page 385 1 department or was there a time when it was 2 generated by another department besides the DEU? 3 A. There was a time the DEU did 4 not exist. But the DEU in 1986 did exist. 5 Q. When did the DEU come into 6 existence? 7 A. I remember 1983 for 8 spontaneous reporting. When they were able to do 9 clinical trial, adverse events was later, I'm not 10 quite sure when. 11 Q. So -- 12 A. But not a lot later than. 13 Q. So you're saying the DEU came 14 into existence in '83 for spontaneous reports? 15 A. Yes. 16 Q. And then later on took over 17 the responsibility of, what, serious clinical 18 trial adverse event reports? 19 A. Right, those that again needed 20 to meet the reporting criteria at the FDA. 21 Q. Does this exhibit indicate to 22 you whether or not this adverse event was a 23 spontaneous adverse event or one that occurred on 24 a clinical trial? Page 386 1 A. This was one that occurred on 2 a clinical trial. 3 Q. How can you tell that? 4 A. By the patient ID, 5 B1Y-MC-HCCJ. 6 Q. In the upper left-hand corner 7 of the page? 8 A. Yes, that was a study. 9 Q. Under describe events, it says 10 patient was hospitalized because of suicidal 11 ideation. Do you see that? 12 A. Yes. 13 Q. On the third page of the event -- 14 I'm sorry, the exhibit, the event term depression 15 was listed; correct? 16 A. Yes. 17 Q. Does that refresh your 18 recollection as to whether or not suicidal 19 ideation mapped to depression? 20 A. That does. 21 Q. And did it at one point in 22 time? 23 A. According to this, yes. 24 Q. Is that your recollection now? Page 387 1 A. Yes. 2 Q. On the front page of the 3 exhibit there's a note that you state is in your 4 handwriting; correct? 5 A. Yes. 6 Q. And that note states or at 7 least asks a question is there not a better term 8 than, quote, depression, unquote; correct? 9 A. Yes. 10 Q. And that is your initial at 11 the bottom of that note; correct? 12 A. Yes. 13 Q. Did you ask anybody 14 specifically about this issue, whether or not 15 there was a better event term to be used other 16 than depression for suicidal ideation? 17 A. I probably discussed it with 18 the physician. 19 Q. Do you recall who that would 20 have been? 21 A. Joe Wernicke. 22 Q. Do you recall what Doctor 23 Wernicke said in response to your question, if 24 anything? Page 388 1 A. I don't, if that's how it 2 remains. 3 Q. Why did you request whether or 4 not there would be a better term to assign to 5 suicidal ideation other than depression? 6 A. To me that was relatively all 7 encompassing. 8 Q. Vague? 9 A. (Witness moves head up and 10 down.). 11 Q. You have to say yes or no. 12 A. Yes. 13 Q. Do you still think that using 14 the term depression to describe suicidal ideation 15 is vague? 16 A. As far as I know, that's the 17 COSTART term, and that's how it's mapped if it 18 hasn't changed. 19 Q. That's not my question, Ms. 20 Ashbrook. Do you still feel that using the event 21 term depression for the actual term of suicidal 22 ideation is vague? 23 A. Yes. 24 Q. To your knowledge are there Page 389 1 any other synonyms under the COSTART dictionary 2 that map to depression? 3 A. Not that I recall. 4 Q. To your knowledge are there 5 any other synonyms that Lilly maps to depression 6 besides suicidal ideation? 7 A. I don't know. 8 Q. Have you heard the term 9 psychotic depression? 10 A. I have heard the term. 11 Q. Do you know if any adverse 12 events related to the use of Fluoxetine or 13 occurring during the use of Fluoxetine have ever 14 been mapped to the event term psychotic 15 depression? 16 A. If other terms have been 17 mapped to psychotic depression? 18 Q. Right. 19 A. I don't know even if psychotic 20 depression is a classification term in the 21 COSTART dictionary, I can't respond to that. 22 Q. Okay. Have you -- what is 23 your understanding of what psychotic depression 24 is? Page 390 1 MR. MYERS: I object to the form, 2 that's a medical question. 3 Q. I know. I'm asking -- you 4 said you heard the term, and I'm asking you what 5 your understanding of what the term means. 6 MR. MYERS: Same objection. If you 7 know, tell her. 8 A. I really cannot give you a 9 medical definition. 10 Q. What context have you heard 11 the term psychotic depression used in? 12 A. I've heard the term. Not in 13 any particular context that I recall. 14 Q. Are you aware of any situation 15 at Lilly where death on Fluoxetine would not be 16 considered serious? 17 A. Not that I'm aware of. 18 Q. Are you aware of any situation 19 at Lilly where a death on Fluoxetine would be 20 considered expected? 21 A. No. 22 MS. ZETTLER: Let's take a break. 23 (A SHORT RECESS WAS TAKEN.) 24 (PLAINTIFFS' EXHIBIT NO. 13 WAS Page 391 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 Q. You had a chance to briefly 4 review the exhibit; correct? 5 A. Yes. 6 Q. Exhibit 13. Do you recognize 7 the documents that comprise Exhibit 13, 8 generally? 9 A. Yes. They're either DEU staff 10 meeting minutes or the DEU, CRA staff meeting 11 minutes. 12 Q. So on those pages of Exhibit 13 13, where it says CRA staff minutes, those would 14 be the DEU, CRA staff minutes? 15 A. Yes. 16 Q. Did you attend these meetings, 17 the staff meetings? 18 A. I attempted to attend the DEU 19 whole staff meetings, I did not attend the CRA 20 staff meetings by and large, maybe one or two. 21 Q. At this time, June 11, 1991 to 22 January of 1992, were you the head of the DEU at 23 that time? 24 A. Yes. Page 392 1 Q. How often were these staff 2 meetings held? 3 A. Weekly. 4 Q. And that's true for the entire 5 DEU staff meetings as well as the DEU, CRA staff 6 meetings? 7 A. They were scheduled, if we had 8 no agenda items, we didn't have a meeting. 9 Q. At the bottom of the first 10 page of Exhibit 13, it says regarding ETR colon. 11 Do you see that? 12 A. Yes. 13 Q. What is ETR? 14 A. It's one of the reports. What 15 does it stand for -- I can't tell you what that 16 acronym stood for right now, I'm sorry. 17 Q. But it refers to a report of 18 some sort? 19 A. Yes. 20 Q. And is that a periodic report, 21 something that was done on a regular interval? 22 A. Yes. 23 Q. After regarding ETR colon, it 24 says expected slash spontaneous deaths do not Page 393 1 qualify for alert reporting, but are sent to the 2 FDA for informational purposes; correct? 3 A. That's what it says. 4 Q. What would be an expected 5 slash spontaneous death to your knowledge? 6 A. I would say if you were a 7 cancer patient, and you died, would probably be 8 expected. 9 Q. Any other examples? 10 A. That's the one that comes to 11 mind. 12 Q. Expected per the FDA 13 regulations and per your earlier testimony is 14 determined by whether or not it's something that 15 has been seen previously in the clinical trials 16 or in the experience with a particular drug; 17 correct? 18 A. That's what I stated. 19 Q. So you're saying that with 20 regards to Fluoxetine, cancer deaths were 21 expected? 22 MR. MYERS: I object to the form, I 23 don't think she's talking about Fluoxetine. 24 Q. Okay. Give me an example Page 394 1 where there would be an expected spontaneous 2 death on Fluoxetine. 3 A. I don't have an example for 4 that. 5 Q. On the second page of the 6 exhibit, it refers to CRA staff meeting minutes 7 from September 10, 1991; correct? 8 A. Yes. 9 Q. Under number two, it says 10 expected event list- Donna distributed the 11 expected event list agreed upon by Doctor 12 Beasley. Do you see that? 13 A. Yes. 14 Q. At that time, in September of 15 1991, was Doctor Beasley working on Fluoxetine? 16 A. 1991, he may have been. 17 Q. Was Doctor Beasley involved in 18 the drug advisory committee meeting preparations 19 for the meeting that was held in September of 20 1991? 21 A. I think he was. 22 Q. At the time that Lilly was 23 preparing for the drug advisory committee meeting 24 on Fluoxetine that occurred on September of 1991, Page 395 1 was Doctor Beasley working on any other Lilly 2 product to your knowledge? 3 A. I can't say with certainty. 4 Q. Do you recall a period of time 5 when the CRAs in the DEU were given the task of 6 assigning expectancy to adverse events that came 7 in on Fluoxetine? 8 A. Of assigning expectancy? 9 Q. To adverse events that came in 10 on Fluoxetine, came into the DEU. 11 A. They would, yes. 12 Q. When was that begun, when were 13 the CRAs given the task of assigning expectancy 14 to adverse event reports that came into the DEU 15 on Fluoxetine? 16 A. I don't know. It wasn't just 17 Fluoxetine, it was no matter what the drug, to do 18 that. 19 Q. But there came a time when -- 20 let's look at Exhibit 13, the second page. It 21 says as of September 11, 1991, all CRAs will 22 begin assigning expectancy for handwritten 23 reports. Do you remember that starting? 24 A. Where are you reading? Page 396 1 Q. The second page of Exhibit 13 2 under number two. 3 A. I see what it says. 4 Q. Do you remember that being the 5 case, that in September of 1991, the CRAs began 6 assigning expectancy for handwritten reports of 7 adverse events? 8 A. That's what it says here. 9 Q. Prior to the CRAs assigning 10 expectancy to adverse event reports, who did 11 that, who assigned expectancy? 12 A. The CRAs worked with the 13 research physicians that had responsibility for 14 the drugs to complete the information on the 15 1639. 16 Q. So it was the physicians who 17 assigned expectancy prior to September of 1991? 18 A. If that's what this says, 19 that's what I would say. 20 Q. Have you ever heard of the 21 term lack of drug effect? 22 A. Yes. 23 Q. What does lack of drug effect 24 mean? Page 397 1 MR. MYERS: I object to the form, 2 that's probably a medical term, but if you know, 3 tell her. 4 A. My understanding of lack of 5 drug effect is that when the patient took it, 6 there was no response. 7 Q. Who determined whether or not 8 a patient was responding to a drug that they were 9 given? 10 A. The physicians that were 11 administering the drug to the patient. 12 Q. The clinical investigators? 13 A. Clinical investigators or the 14 physicians, after the products were marketed, 15 physicians that saw the patients. 16 Q. You mean the independent 17 private physicians that were prescribing the 18 drug? 19 A. Yes. 20 Q. Was that determination ever 21 made by Lilly physicians in Indianapolis with 22 regards to spontaneous events that came in? 23 A. I can't answer that. 24 Q. Why can't you answer it, Page 398 1 because you don't know? 2 A. I don't know. 3 Q. How about lack of efficacy, 4 have you ever heard of that term? 5 A. I've heard of the term. 6 Q. Can you tell me what your 7 understanding of what lack of efficacy means? 8 MR. MYERS: Notwithstanding her 9 understanding, it's a medical term, and I object 10 to the form, but tell her what you know. 11 A. I know that to be a term, I 12 don't know that to be an event term. Lack of 13 efficacy would mean the product -- the patient 14 didn't respond to the product. 15 Q. Similar to lack of drug 16 effect? 17 A. Similar. 18 Q. Do you know what the 19 difference is between lack of drug effect and 20 lack of efficacy is, if any? 21 A. With my knowledge, I can't 22 differentiate. 23 Q. During the period of time from 24 June of 1991 through the Fall of 1992, how much Page 399 1 of the DEU's time was spent on -- I'm sorry, the 2 beginning of 1992, how much of the DEU's time was 3 spent on adverse events related to the use of 4 Fluoxetine? 5 A. What do you mean by spent on 6 adverse events? 7 Q. The DEU -- it's my 8 understanding that you testified earlier that the 9 DEU handled adverse events for all Lilly drugs 10 that were being produced or sold; correct? 11 A. Yes, that's correct. 12 Q. Was there a percentage or 13 larger percentage of adverse events that were 14 being dealt with by the DEU or coming into the 15 DEU related to the use of Fluoxetine as opposed 16 to other Lilly drugs during this period of time? 17 A. Yes. 18 Q. What percentage of the time at 19 the DEU would you estimate was being spent on 20 Fluoxetine adverse events as opposed to other 21 Lilly products during this period of time? 22 A. I can't answer with a percent 23 of time. 24 Q. Would you say more than half Page 400 1 the time of the DEU employees was being devoted 2 during this period of time to Fluoxetine adverse 3 events? 4 A. I could better answer that 5 without people in the DEU, how many worked on 6 Fluoxetine, but that doesn't give you a percent. 7 Q. Okay. How many people -- 8 let's put it this way: How many people were 9 working under you during this period of time in 10 the DEU? 11 A. In the DEU, at that time, 12 there were twenty folks. 13 Q. And how many of those people 14 were working on Fluoxetine? 15 A. That were totally devoted to 16 it, three CRAs, one DEA, we had two data 17 encoders, but they encoded for everybody. 18 Q. So you had three CRAs and one 19 DEA? 20 A. Yes. 21 Q. That were totally, a hundred 22 percent, devoted to adverse events related to 23 Fluoxetine? 24 A. Yes. Page 401 1 Q. How about people who had 2 part-time responsibility with regards to 3 Fluoxetine during that period of time? 4 A. We had one person focused on 5 international, took care of all of international. 6 So I can't give you a percent of that person's 7 time. 8 Q. Okay. Anybody else? 9 A. Those were the full-time 10 people. If we needed help, no matter what the 11 product was, everybody pitched in to help. But 12 that wasn't the standard operating procedure. 13 Q. How about the other people 14 that weren't a hundred percent devoted to 15 Fluoxetine, were there any other people out of 16 those twenty people that were devoted to just one 17 drug or one product of Lilly's during that time 18 period? 19 A. Yes. 20 Q. Okay. How many? 21 A. How many what? 22 Q. How many people had -- how 23 many other people within that twenty had 24 assignments related to only one other product of Page 402 1 Lilly's other than Fluoxetine? 2 A. There were five CRAs. 3 Q. Were they all on the same 4 product? 5 A. No, they had -- 6 Q. Did they each have their own 7 individual drug? 8 A. Yes. 9 Q. And those drugs differed from -- 10 between the five other CRAs? 11 A. Yes. 12 Q. So as far as the manpower 13 distribution within the DEU at that period of 14 time, the most manpower was devoted to Fluoxetine 15 adverse events? 16 A. Yes. 17 Q. Why was that? 18 A. Why was that? 19 Q. Right. Why is it that you 20 needed so many people working specifically on 21 Fluoxetine during this period of time? 22 A. To process the adverse events 23 that came in on Fluoxetine. 24 Q. So there were a number of Page 403 1 adverse events coming in that required that many 2 people to process those adverse events as they 3 came in, such a number of adverse events that it 4 required that many people to work on it? 5 A. Yes. 6 Q. Have you heard of the Citizens 7 Commission on Human Rights? 8 A. Citizens Commission on Human 9 Rights, yes. 10 Q. Have you heard of the Church 11 of Scientology? 12 A. Yes. 13 Q. Can you tell me what the 14 Citizens Commission on Human Rights is? 15 A. I get foggy between the two. 16 Q. You're saying they're related? 17 A. They're related. So if you 18 want a specific on it, I probably can't give you 19 that. 20 Q. Give me your general 21 understanding of what those two entities are. 22 A. Those two entities are -- it's 23 one of their beliefs that they are opposed to 24 psychiatrists and psychiatric medicine. Page 404 1 Q. Okay. Anything else that 2 you're aware of or anything else that encompasses 3 your understanding of what they are or what their 4 purpose is? 5 A. With their opposition to 6 psychiatric medicine, they would prefer that 7 people didn't take it. 8 Q. Okay. You don't have to worry 9 about offending me, I'm not a part of either one 10 of those groups, Ms. Ashbrook, so you can be as 11 frank as you like in your answer. Were you ever 12 aware of allegations that either CCHR or the 13 Church of Scientology was trying to flood the FDA 14 adverse events or adverse drug data base, adverse 15 drug event data base? 16 Q. Trying to do what? 17 A. Trying to flood it. 18 MR. MYERS: With water? 19 Q. With adverse events. 20 A. Who? 21 Q. The CCHR. 22 A. The CCHR was trying to flood -- 23 Q. In other words, file false 24 adverse event reports. Page 405 1 A. Yes. 2 Q. You have. Who did you hear 3 that from? 4 A. I can't pinpoint a person. 5 Q. Was it somebody within the 6 medical division? 7 A. I don't recall. I know there 8 was a media blitz that I was aware of that they 9 did, I mean I can't tell you if that's when I 10 became cognizant of it or I heard about it 11 previous to that. 12 Q. Okay. What, if anything, was 13 done at Lilly to investigate that allegation? 14 A. To investigate? 15 Q. Whether or not that CCHR or 16 the Scientologists were trying to skew or flood 17 the FDA data base regarding adverse event reports 18 on Fluoxetine? 19 A. What did we do? 20 Q. Right. 21 A. I don't know what we did. 22 Q. Do you know that something was 23 done in response to that allegation by Lilly? 24 A. I mean we conversed with the Page 406 1 media. 2 Q. About this specific issue? 3 A. About the issue with the 4 Church of Scientology and the CCHR. 5 Q. I'm just concerned about the 6 allegation that either CCHR or the scientologists 7 were filing false adverse event reports with the 8 FDA to try to make it appear that there were more 9 adverse events that were being reported on 10 Fluoxetine than were actually happening, okay. 11 And that's what I want to narrow it down to. 12 A. Okay. 13 Q. You were aware of that 14 allegation; correct? 15 A. I was aware of that. 16 Q. To your knowledge, did Lilly 17 do anything in response to either investigate the 18 validity of that allegation or to counteract that 19 allegation in any way? 20 A. From where I was in the drug 21 epidemiology unit, we continued to process all 22 those adverse events that came in. There was no 23 way we could tell where they were coming from, so 24 I mean we processed them. Because -- if they Page 407 1 were flooding the FDA, I can't respond to that. 2 Q. To your knowledge, has either 3 CCHR or the scientologists submitted any adverse 4 event reports to Eli Lilly regarding Fluoxetine? 5 A. We would not know that. With 6 our spontaneous reports, we would not know that. 7 Q. To your knowledge has the 8 allegation that either CCHR or the scientologists 9 were trying to flood the FDA data base by filing 10 false reports ever substantiated? 11 A. Could you please repeat that a 12 little more slowly? 13 Q. Sure. To your knowledge, has 14 the allegation that the CCHR or the 15 scientologists were filing false adverse event 16 reports with the FDA to try to skew or flood the 17 data base with event reports regarding 18 Fluoxetine, was that ever substantiated? 19 A. I don't know that. 20 Q. Did either Doctor Dobbs or 21 Doctor Hardison work on the response to the BGA 22 questions to your knowledge? 23 A. One of the previous exhibits, 24 Exhibit 5 -- Page 408 1 Q. Okay. 2 A. -- came from Doctor Hardison. 3 Q. Okay. How about Doctor Dobbs, 4 to your knowledge did Doctor Dobbs work on any of 5 Lilly's responses to BGA questions regarding 6 Fluoxetine? 7 A. I don't see her name on the 8 addressee list. I don't know if she was still 9 here, I don't recall. 10 (PLAINTIFFS' EXHIBIT NO. 14 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Have you had a chance to 14 review Exhibit 14? 15 A. I have reviewed it cursory. 16 Q. Do you recognize the documents 17 that make up this exhibit? 18 A. I've seen these documents. 19 Q. Can you tell me generally what 20 these are? 21 A. The early termination 22 summaries or 1639s that were filed on patients 23 that have participated in Fluoxetine clinical 24 trials. Page 409 1 Q. You talked about one suicide 2 that you were aware of on a placebo wash-out 3 phase of a study; correct? 4 A. (Witness moves head up and 5 down.). 6 Q. When was that approximately 7 that that occurred, do you recall? 8 A. Somewhere prior to the initial 9 filing of the NDA in September of '83. 10 Q. And I believe it was your 11 testimony yesterday that other than that one 12 suicide in the placebo wash-out phase prior to 13 September of 1993, you did not recall any other 14 completed suicides that occurred during clinical 15 trials on Fluoxetine prior to that date? 16 A. I'm sorry, on your date, I 17 didn't hear your date. 18 Q. The September of '83 19 submission of the NDA to the FDA, prior to that 20 you were only aware of one completed suicide on 21 Fluoxetine in clinical trials? 22 A. That I recall, yes. 23 Q. What about suicide attempts? 24 A. Again, there was no cases that Page 410 1 I could recall. 2 Q. If you could look at about the 3 eighth page in, which is PZ 516 2485. Do you see 4 that, it's dated December 6th, 1982? 5 A. Yes. 6 Q. Looks like a memorandum from 7 Giselle Soyez? 8 A. Yes. 9 Q. Regarding Doctor Abuzzahab's 10 file? 11 A. Yes. 12 Q. It talks about a patient on 13 one of Doctor Abuzzahab's studies that took an 14 overdose of chloral hydrate; correct? 15 A. Yes. 16 Q. Is there any way to tell 17 whether or not this patient was on Fluoxetine at 18 the time they took the chloral hydrate? 19 A. I can't tell from this. 20 Q. But the overdose occurred 21 during the clinical trial; correct? 22 A. According to -- it's an 23 investigator, and it refers to a patient and 24 their number. Page 411 1 Q. Okay. Would this act be 2 considered a suicide attempt, to your knowledge? 3 MR. MYERS: I object to the form, 4 that's a medical psychiatric question. If you 5 know, tell her. 6 Q. If you know. 7 A. I would take it literally, and 8 it was referred to as an overdose. 9 Q. What's the difference between 10 an overdose and suicide attempt, to your 11 knowledge? 12 MR. MYERS: Same objection, that's a 13 medical question. 14 A. I can't, as a layman, I don't 15 differentiate or I can't differentiate. 16 Q. Do you have a personal opinion 17 as to whether or not somebody taking an 18 intentional overdose of pills is a suicide 19 attempt? 20 MR. MYERS: Same objection. Even 21 though you're asking personally, it still 22 requires medical expertise. 23 Q. Do you have an opinion? 24 A. It would be difficult to say. Page 412 1 Q. Why? 2 A. They could have taken too many 3 pills because they had forgotten they had already 4 taken it, taken it again. 5 Q. It could have been accidental? 6 A. It could have been accidental. 7 Q. Could have been a prescription 8 error? 9 A. I can't -- 10 Q. I'm not talking about this 11 specific instance. Were you aware that as of 12 late '89, clinical research physicians at Lilly 13 wanted the intentional overdoses mapped to the 14 event term overdose as well as accidental 15 overdoses? 16 MR. MYERS: I object to the form, that 17 assumes facts that won't be in evidence. But if 18 you know the answer to that, tell her. 19 A. I don't know the answer to 20 that. 21 Q. Are you aware that at any time 22 intentional overdoses were mapped to overdose, 23 just straight overdose, as well as other forms of 24 overdoses, including accidental overdoses and Page 413 1 prescription errors? 2 A. Were mapped to? 3 Q. Overdose. 4 A. I don't know that. 5 Q. If that were the case, would 6 you think that would be appropriate? 7 MR. MYERS: I object to the form, that 8 may again be a medical question. 9 A. It would be the physician's 10 decision. 11 Q. Earlier we talked about your 12 concerns, at least as of 1986, as to mapping 13 suicidal ideation to the event term depression, 14 and it being vague. Do you recall that? 15 A. Yes. 16 Q. Do you feel that the term 17 overdose in and of itself, without a descriptor 18 such as intentional or accidental, is vague? 19 MR. MYERS: Well, I object to the form 20 of the question, Nancy, for this reason: If 21 that's what it mapped to, and whatever the 22 dictionary was, that's what it mapped to. 23 MS. ZETTLER: I'm asking a general 24 question. If she thinks that using the term Page 414 1 overdose to include the synonyms of intentional 2 overdose, accidental overdose, prescription 3 error, et cetera, to be vague. 4 A. My personal opinion, I would 5 not consider that as vague. 6 Q. Why not? 7 A. Because overdose to me says 8 they ingested a drug. No matter how, but I could 9 still figure out they had ingested a drug larger 10 than was prescribed. 11 Q. Okay. Would you agree with me 12 that often when somebody takes an overdose, an 13 intentional overdose, of a substance, be it a 14 drug or alcohol or anything that you can ingest, 15 that that is at least related in some way to 16 wanting to harm yourself? 17 MR. MYERS: Let me object to the form 18 of the question. To the extent it's a 19 hypothetical, it doesn't give enough facts to 20 make any opinion, and any opinion that it may 21 call is probably an expert opinion, a physician 22 opinion. But if you know, tell her. 23 A. I don't have an opinion on 24 that. Page 415 1 Q. Is it fair to say that some 2 people commit suicide by taking overdoses of 3 drugs, would you agree with me on that? 4 A. Yes. 5 Q. Okay. Would you agree with me 6 that if you have an issue as to whether or not 7 people are harming themselves as a result of 8 ingesting a drug such as Fluoxetine, and I don't 9 mean overdosing on Fluoxetine, that you would 10 want to look at all different ways that somebody 11 would harm themself on a drug? 12 MR. MYERS: I object to the form, it's 13 hypothetical, not enough facts, and it calls for 14 some kind of an expert opinion. If you know, 15 tell her. 16 A. You'll have to repeat the 17 question. 18 Q. Sure. We have -- would you 19 agree with me that some people, while on 20 Fluoxetine, have committed suicide, regardless of 21 causal relationship of Fluoxetine and the 22 suicide, there have been people that have taken 23 Fluoxetine that have committed suicide? 24 A. I agree with that statement. Page 416 1 Q. Okay. Would you agree with me 2 that the suicides have been committed in various 3 ways by various methods? 4 A. What do you mean by various 5 methods? 6 Q. Some people have blown their 7 brains out, some people have taken overdoses of 8 drugs, I have a client who jumped in front of a 9 train. That's what I mean, the ways that they've 10 killed themselves have varied, without a causal 11 relationship to the drug. 12 A. Suicides can be committed in a 13 variety of ways. 14 Q. In your experience in the DEU, 15 have you become aware of suicides that have been 16 committed by people taking Fluoxetine generally, 17 would you have become aware of suicides that have 18 been committed by people who were on Fluoxetine; 19 correct? 20 A. Yes. 21 Q. Have you become aware of some 22 of the various methods that were employed to 23 commit suicide by these people? 24 A. No. Page 417 1 Q. You have not seen -- you are 2 not aware of any methods that were employed by 3 any of these people that have committed suicide 4 while on Fluoxetine? 5 A. (Witness moves head from side 6 to side.). 7 Q. You're aware that Joseph 8 Wesbecker committed suicide, are you not? 9 A. Yes, I am. 10 Q. And you're aware of how he 11 committed suicide, are you not? 12 A. I don't know how he committed 13 suicide. 14 Q. If I were to tell you that he 15 shot himself in the head, would that surprise 16 you? 17 MR. MYERS: I object to the form, what 18 do you mean surprise her? 19 Q. Given the facts that she 20 knows, that people were shot by him. 21 MR. MYERS: I object -- 22 Q. If I were to represent to you, 23 Ms. Ashbrook, that Joseph Wesbecker shot twenty 24 people and then blew his own brains out, okay, Page 418 1 would that be acceptable to you, my 2 representation, if we can start it from my 3 representation? 4 MR. MYERS: What do you mean would 5 your representation be acceptable for her, for 6 what purpose? 7 MS. ZETTLER: Just for the purposes of 8 discussing various suicide attempts that have 9 been employed by people on Fluoxetine. 10 MR. MYERS: Assume that what she told 11 you is correct, that he shot twenty people and 12 then he shot himself. Go ahead. 13 Q. And your testimony is that you 14 are previously not aware of any of the methods 15 that have been employed by people on Fluoxetine 16 to commit suicide; correct? 17 A. While I was in the DEU, I did 18 not read the 1639s that were written. 19 Q. Yet it's still your opinion 20 that all suicides that were committed by people 21 on Fluoxetine would be considered serious adverse 22 events, right? 23 A. I know that people committed 24 suicide, and they had taken Fluoxetine at some Page 419 1 point. I don't know that they were on Fluoxetine 2 when they did it. 3 Q. That's not my question. If an 4 adverse event was reported about somebody who was 5 on Fluoxetine who had killed themself, okay, 6 whether or not it would be considered a serious 7 adverse event, regardless of causal relationship. 8 A. Would that be considered a 9 serious adverse event? 10 Q. Right, a completed suicide. 11 MR. MYERS: I object to the form 12 because that's controlled by regulation. But if 13 you know the answer, tell her. 14 A. That was a death, so therefore 15 it was a serious outcome. 16 Q. Okay. To your knowledge, has 17 there ever been a time when suicide was an 18 expected adverse event on Fluoxetine? 19 A. Again, the term suicide, and 20 the one that I recollect, was when a patient was 21 on a placebo wash-out period before they were in 22 the study. 23 Q. You've already testified that 24 to your knowledge other people have committed Page 420 1 suicide who were taking Fluoxetine or at least 2 had taken Fluoxetine at some period of time; 3 correct? 4 A. We have that information in 5 our data base. 6 Q. And is it your testimony that 7 spontaneous adverse events related to suicide and 8 with people who have taken Fluoxetine have been 9 reported to Lilly? 10 MR. MYERS: Have those come in by way 11 of spontaneous report? 12 MS. ZETTLER: Right. 13 A. Yes. 14 Q. Okay. To your knowledge, at 15 any time has an adverse event of suicide, 16 completed suicide, been considered expected by 17 Eli Lilly? 18 MR. MYERS: When you say considered, 19 you mean reported as serious expected? 20 MS. ZETTLER: Well, I'm talking about 21 before it's reported by Lilly to the FDA, I'm 22 talking about is it considered serious under the 23 regulations, and expected under the regulations. 24 A. We're getting out of my league Page 421 1 that I can respond to that. 2 MR. MYERS: If you know, tell her, and 3 if you don't know, tell her that. 4 A. I don't know. 5 Q. So your testimony is that you 6 were the head of the DEU, and you don't know if 7 there was ever a time that suicide was ever 8 considered an expected adverse event by Eli 9 Lilly, is that your testimony? 10 A. Yes. 11 Q. Who would know that? 12 A. The physicians. 13 Q. When you say the physicians, 14 who do you mean specifically? 15 A. The clinical research 16 physicians and the CRAs that are working on 17 Fluoxetine. 18 Q. You mean Charles Beasley? 19 MR. MYERS: For instance? 20 MS. ZETTLER: For instance. 21 A. For instance, yes. 22 Q. John Heiligenstein? 23 A. For instance. 24 Q. David Wheadon? Page 422 1 A. For instance. 2 Q. Jamie Street? 3 A. I don't recall if she worked 4 on Fluoxetine. 5 Q. If she worked on Fluoxetine, 6 should she know whether or not suicide was 7 considered an expected adverse event? 8 A. Yes, if she did. 9 Q. How about Leigh Thompson, 10 would he know whether or not suicide was 11 considered an expected adverse event on 12 Fluoxetine? 13 A. I don't know. 14 Q. Any other clinical research 15 physicians at Lilly that would know whether or 16 not it was considered an adverse event on 17 Fluoxetine -- 18 MR. MYERS: Who. 19 Q. Whether or not it was 20 considered an adverse event on Fluoxetine? 21 MR. MYERS: An expected adverse event? 22 MS. ZETTLER: Yes, I'm sorry. 23 A. Are there any other 24 physicians? Page 423 1 Q. Right. 2 A. Currently I think it's Doctor 3 Blomgren and probably David Goldstein. 4 Q. Okay. How about Doctor 5 Wernicke, not at this time, but would he have 6 been aware of whether or not suicide was 7 considered an expected adverse event? 8 A. I would think so. 9 Q. How about Doctor Stark? 10 A. The whole way of looking at 11 adverse events from the FDA changed between when 12 Doctor Stark was involved and later, so I don't 13 know what the criteria were at that time for 14 reporting, so I'm not sure what he knew. He 15 would know what were the reporting criteria at 16 that time. 17 Q. When you say the reporting 18 criteria, you mean the FDA reporting criteria or 19 Lilly's reporting criteria? 20 A. The FDA. 21 Q. So the FDA regulations changed 22 as to what was considered serious and expected, 23 things of that nature? 24 A. Right, since we've been Page 424 1 studying Fluoxetine. 2 (A SHORT RECESS WAS TAKEN.) 3 (PLAINTIFFS' EXHIBIT NO. 15 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to 7 review Exhibit 15? 8 A. Yes, I reviewed it. 9 Q. Are you familiar with this 10 exhibit? 11 A. I'm a CC on this message. 12 Even reviewing it, I'm having trouble recalling 13 it. 14 Q. Okay. It's an E-Mail from Max 15 Talbott dated May 8, 1991; correct? 16 A. That's correct. 17 Q. And as you stated a couple of 18 seconds ago, you are listed as a CC on that 19 E-Mail; correct? 20 A. Yes. 21 Q. Would you have read this if it 22 came across your computer or your desk? 23 A. Yes, I would have read it. 24 Q. The second point on the E-Mail Page 425 1 says with the surfacing of the first, quote, 2 direct from blank, end quote, ADR report. Do you 3 know what they're referring to there? 4 A. No, I don't. 5 Q. Would this be CCHR adverse 6 event reports? 7 A. I don't know. 8 Q. If we could go back to Exhibit 9 13, about the tenth page in, page Pz 1556 2163. 10 It's about ten pages down. I'm sorry, I did it 11 by date instead of Pz number, that's why it's 12 about ten pages back. It's CRA staff minutes 13 dated December -- I'm sorry, November 7th, for a 14 meeting that was held October 5th, 1991; correct? 15 A. Yes. 16 Q. On the fourth point down, 17 number four, it says Bob is finishing details for 18 the procedure addressing actively suicidal phone 19 calls. What are actively suicidal phone calls? 20 A. This referred to patients that 21 called in themselves, not their physicians, and 22 they were talking about committing suicide. 23 Q. Do you recall that happening, 24 patients would call in that were actively Page 426 1 suicidal? 2 A. That would rarely happen. 3 Q. But it did happen? 4 A. Yes. 5 Q. Did it happen on Fluoxetine? 6 A. Yes. 7 Q. What was done in response to a 8 phone call by somebody who was actively suicidal 9 on Fluoxetine? 10 A. The folks in the DEU were by 11 and large nurses by training, and they would talk 12 to the patient, we would attempt to calm them 13 down, we would attempt to find out what city they 14 were from, and we would attempt to find a 15 doctor's name so that we could either, one, 16 notify a law enforcement agency in that state or 17 in that city if we could find it out, or notify 18 their doctor so they could get in touch with 19 them. 20 Q. To your knowledge, has anybody 21 committed suicide either during or shortly after 22 a phone call to Lilly talking to somebody at the 23 DEU? 24 A. I don't know. Page 427 1 Q. Approximately how many 2 occasions did this happen, that somebody called 3 in who was actively suicidal while you were in 4 the DEU? 5 A. Very rarely. 6 Q. Less than ten? 7 A. Oh, yes. 8 Q. Less than five? 9 A. Probably five or less. 10 Q. Why did the DEU or the CRA 11 staff at least feel it was necessary to come up 12 with a procedure to address such calls if it 13 happened so rarely? 14 A. Because when it happened, we 15 needed to take action. 16 Q. I'm sorry, I didn't mean to 17 interrupt you. 18 A. Just as a concerned person, 19 they didn't want anything to happen to anybody 20 that was on the phone with them. 21 Q. Was a written procedure set 22 forth to handle these situations? 23 A. The term procedure in there, 24 as I recall, we were attempting to work with the Page 428 1 suicide hotline here in town, if we could get the 2 calls referred to them somehow, so people that 3 were really trained in handling patients that 4 were actively suicidal. So I don't know that 5 procedure here means taken verbatim. 6 Q. To your knowledge were there 7 ever any written directives or procedures that 8 were created as a result of actively suicidal 9 patients calling Lilly on how to deal with that 10 situation? 11 A. I know we talked about it. I 12 don't know for a fact if it was written down. 13 Q. Do you know if an agreement 14 was reached with the suicide hotline in town here 15 that calls would be referred to them? 16 A. I don't recall. 17 Q. Do you recall what suicidal 18 hotline you were talking to here in town? 19 A. No. 20 Q. Under number eight it says 21 Carol will follow up with Max regarding the 22 labels for reports of expected deaths. Do you 23 see that? 24 A. I see that. Page 429 1 Q. What are labels for reports of 2 expected deaths? 3 A. I don't know. 4 Q. What are DES reports, under 5 number three? 6 A. A DES is diethylporpion. 7 Q. Okay. So that's another Lilly 8 drug? 9 A. A former product. 10 Q. Who were the CRAs in the DEU 11 at this time that were working specifically on 12 Fluoxetine? 13 A. What date is this, 1991. Bob 14 Hunt, Mindy Gould. I think Donna was. 15 Q. Donna Pearson? 16 A. Donna Pearson, yes. 17 Q. Anybody else on that list? 18 A. At that point in time, those 19 are the ones that I recall. 20 Q. On the next page of the 21 exhibit, CRA staff minutes from a meeting held 22 November 12, 1991, under section two it says 23 Mindy provided an example of what the new 24 proposed, quote, pull slips, unquote, will look Page 430 1 like. What are pull slips? 2 A. I don't recall what those look 3 like. 4 Q. Do you recall what they are? 5 A. No, I don't recall what they 6 are. 7 Q. The next line of the section 8 says the new slip will have two sections, one for 9 pulled reports and one for reports added to the 10 mailing. Does that refresh your recollection as 11 to what pull slips are? 12 A. From what it says here, I 13 would think it has to do with reports that we did 14 not send that week because we didn't have 15 information to make a complete report. 16 Q. So reports were pulled if you 17 didn't feel you had enough information? 18 A. If we could send them still 19 within the reporting guidelines, yes. 20 Q. And when you say the reporting 21 guidelines, you mean the FDA reporting 22 guidelines? 23 A. Yes. 24 Q. On the next page of the Page 431 1 exhibit, which is CRA staff minutes for meeting 2 dated November 19, 1991, under number five it 3 says COSTART changes were discussed. It was the 4 concensus of the group that searching and 5 gathering data would be more accurate if the DEN 6 data base was remapped with these changes 7 systematically. Do you recall the DEN data base 8 being remapped to reflect changes in COSTART in 9 November of 1991 or thereafter? 10 A. I know this was a topic of 11 discussion. What was your question? 12 Q. Do you know if the DEN data 13 base adverse event terms were remapped to reflect 14 changes in COSTART? 15 A. No. 16 Q. No, you don't know or no, they 17 were not? 18 A. No, they were not. 19 Q. Number seven, it says Mindy 20 will look into the event terms of injury, comma, 21 accident, paren, now accidental injury, close 22 paren, and intentional injury. Do you see that? 23 A. I see that. 24 (DISCUSSION OFF THE RECORD.) Page 432 1 MS. ZETTLER: Could you read back the 2 last question? 3 (THE COURT REPORTER READ BACK THE 4 REQUESTED TESTIMONY.) 5 Q. Do you recall inconsistencies 6 in assigning these event terms as being an issue 7 at any time? 8 A. What do you mean being an 9 issue? 10 Q. Being a problem. 11 A. From what I read here, we 12 wanted to make sure that there was a 13 differentiation between the two. 14 Q. Okay. What do you mean by a 15 differentiation between the two? 16 A. If something was an accidental 17 injury, would be different than intentional 18 injury. I don't know if they were together 19 previously. 20 Q. Do you recall what synonyms 21 fell under intentional injury? 22 A. No, I don't. 23 Q. Do you recall what synonyms 24 fell under accidental injury? Page 433 1 A. No, I don't. 2 Q. If you would look four pages 3 back from that page, which is Pz 1556 2153. Do 4 you see that page? 5 A. Yes, this page. 6 Q. I wanted to make sure you 7 found it. 8 A. Yes. 9 Q. Under number eight, it says 10 Mindy sent a message to all physicians to get 11 their input on using intentional injury for 12 self-inflicted injuries rather than accidental 13 injury. Do you see that? 14 A. I see that. 15 Q. Do you recall that being a 16 case where self-inflicted injuries were mapped to 17 accidental injuries prior to December of 1991? 18 A. No. 19 Q. Can you give me an example of 20 self-inflicted injury that would be accidental? 21 A. No. 22 Q. To your knowledge is the issue 23 of mapping self-inflicted injuries to accidental 24 injury a Fluoxetine related issue? Page 434 1 A. I can't state that positively. 2 Q. On the next page of the 3 exhibit, which is Pz 1556 2150. 4 A. Yes. 5 Q. Looks like CRA staff meeting 6 minutes from a meeting held January 7, 1992; 7 correct? 8 A. That's correct. 9 Q. Under the first topic 10 discussed it states an epidemiology pilot project 11 was discussed in the Prozac strategy meeting 12 yesterday. Do you recall an epidemiology pilot 13 project as being discussed in January of 1992? 14 A. No. 15 Q. Do you recall an epidemiology 16 pilot project ever being discussed with regards 17 to Prozac? 18 A. Epidemiology pilot project, 19 no. 20 Q. Do you know what an 21 epidemiology pilot project is? 22 A. No. 23 Q. Under number seven it states 24 that Mindy will be sending a message to the Page 435 1 affiliates regarding a change in mapping 2 self-inflicted injury. Any self-inflicted injury 3 that is not a suicide attempt will map to 4 intentional injury instead of accidental injury. 5 Do you see that? 6 A. I see that. 7 Q. Can you give me an example of 8 what a self-inflicted injury that is not a 9 suicide attempt would be? 10 MR. MYERS: I object to the form, I 11 think that's maybe a medical or psychiatric type 12 of opinion. If you know, if you can give an 13 example, give her one. 14 A. I can't give an example. 15 Q. Do you know why self-inflicted 16 injuries that were not suicide attempts were 17 mapped to accidental injuries prior to January of 18 1992? 19 A. No, I don't. 20 Q. Can you go back a couple more 21 pages, to Pz 1556 2148, please. 22 A. I have that. 23 Q. Under number six, at the 24 bottom of the page, it states the new dictionary Page 436 1 does not contain all the synonym terms that are 2 in the DEN dictionary. Do you see that? 3 A. I see that. 4 Q. Can you tell me what the DEN 5 dictionary is? 6 A. I don't know what a separate 7 DEN dictionary is. 8 Q. Do you know what Ms. McKenzie 9 is referring to here when she talks about the DEN 10 dictionary? 11 MR. MYERS: Well, unless she knows 12 independently, I object to the form because that 13 would be speculation as to what she means. 14 MS. ZETTLER: That's why I asked her 15 if she knew, Larry. 16 A. No, I don't. 17 Q. To your knowledge, were event 18 terms that had been used in DEN, in the DEN data 19 base, in other words if an event term comes in -- 20 an event comes in and the term is assigned and 21 the information is entered into the DEN data 22 base, okay. To your knowledge had those event 23 terms ever been changed in response to a change 24 to any of the Lilly dictionary or the COSTART Page 437 1 dictionary, I mean across the board, the computer 2 edits, things of that nature? 3 A. Did a computer change go and 4 change everything? 5 Q. Right. 6 A. In the DEN data base? 7 Q. Right. For Fluoxetine, I can 8 narrow it down to Fluoxetine. 9 A. No. 10 Q. Was there ever an 11 across-the-board change on all adverse events 12 that were stored in the DEN data base, for 13 instance the remapping of self-inflicted 14 nonsuicide attempt injuries to intentional 15 injuries from accidental injuries, was that done 16 across the board or was that only done 17 prospectively once the decision to make the 18 change was made? 19 A. It was done prospectively. 20 Q. What would be done with the 21 information that had been previously stored in 22 the DEN data base, how would the difference in 23 the mapping of event terms be noted or kept track 24 of? Page 438 1 A. There was kind of a screen 2 that would come on if you're searching for this 3 term. Prior to then, you may want to look at 4 these terms, would lead them back into what they 5 may have been. 6 Q. Okay. So if you were 7 searching for self-inflicted injuries that were 8 not suicide attempts, and you entered that term 9 into the data base to do a search on it, the 10 computer would alert you that at some point in 11 time self-inflicted injuries could have been 12 mapped to accidental injuries? 13 A. That you may want to look 14 under, yes. I'm not sure of how detailed it 15 went, but there had to be a clue, there has to 16 be, so you can go back. 17 Q. Are you aware of the 18 duplicating mode that was used in the DEN, have 19 you ever heard that before? 20 A. The duplicating mode? 21 Q. Right. 22 A. No. 23 Q. How were duplicate reports 24 handled, duplicate adverse event reports, handled Page 439 1 in the DEU? 2 A. What do you mean? 3 Q. There would be occasion when 4 you would get more than one report on an adverse 5 event; correct, from two different sources? Did 6 that ever happen, to your knowledge, that you 7 would get more than one report on the same event? 8 A. What do you mean by the same 9 event? 10 Q. Say somebody suffered an 11 adverse event on Fluoxetine, okay. Was there 12 ever an occasion where that adverse event was 13 reported to Lilly by more than one source? 14 A. That could happen. 15 Q. Okay. And those -- could it 16 happen that those sources could be independent of 17 each other? 18 A. Could be. 19 Q. Were you aware of that ever 20 happening? 21 A. Yes, that happened. 22 Q. Okay. When that happened, 23 what did Lilly do to assure that that event was 24 not reported twice to the FDA if it was Page 440 1 reportable? 2 A. I don't know what procedure 3 was used, there was a procedure, though. 4 Q. Was it a written procedure? 5 A. I think it was. 6 Q. Do you know where that written 7 procedure would have been maintained? 8 A. I'm sorry? 9 Q. Do you know where that written 10 procedure would have been maintained, in what 11 document? 12 A. Procedures manual. 13 (PLAINTIFFS' EXHIBIT NO. 16 WAS 14 MARKED FOR IDENTIFICATION AND 15 RECEIVED IN EVIDENCE.) 16 Q. Have you had a chance to 17 review Exhibit 16? 18 A. Yes, I have reviewed Exhibit 19 16. 20 Q. And generally it's a group of 21 adverse events related to Fluoxetine; correct? 22 A. Yes. 23 Q. The first adverse event report 24 in the exhibit is dated in the upper right-hand Page 441 1 corner reaction onset date of March 19, 1985; 2 correct? 3 A. Yes. 4 Q. And under the description it 5 states the patient took an intentional overdose 6 of ten aspirin. Do you see that? 7 A. Yes. 8 Q. The event term on the second 9 page is listed as drug overdose; correct? 10 A. That's what it says. 11 Q. Can you tell if this is a 12 spontaneous report or a report of an adverse 13 event that occurred during a clinical trial? 14 A. This is an event that occurred 15 during the clinical trial. 16 Q. The second report in the 17 exhibit is dated reaction onset date of 4-12-85; 18 correct? 19 A. Yes. 20 Q. And it says under description 21 physician stated that patient had switch effect, 22 pressure of speech, not thinking clearly, 23 thoughts of suicide; correct? 24 A. That's what it says. Page 442 1 Q. Goes on to say was labile, was 2 hitting herself with rocks, period, hypomanic; 3 correct? 4 A. Yes. 5 Q. The event term listed on the 6 second page of the form is hypomanic; correct? 7 A. That's correct. 8 Q. It doesn't say anything about 9 having suicidal ideation in there, does it? 10 A. It does not. 11 Q. It doesn't say anything about 12 self -- about her hitting herself with rocks; 13 correct? 14 MR. MYERS: Under event term. 15 MS. ZETTLER: Right. 16 A. Under event term, it does not. 17 Q. Do you know why that is, why 18 suicidal ideation is not listed as an event term 19 on this form? 20 A. I don't know. 21 Q. On the next report, it's dated 22 11-7-85; correct? 23 A. Yes. 24 Q. And on the descriptive event Page 443 1 it says patient was hospitalized on November 7, 2 1985 because of increased symptoms of depression, 3 paren, agitation, insomnia and confusion, close 4 paren; correct? 5 A. That's what it says. 6 Q. And then on the next page 7 event term listed depression. 8 A. Yes. 9 Q. Does this refresh your 10 recollection as to what other synonyms are listed 11 under the classification term depression? We 12 talked earlier about suicidal ideation. 13 MR. MYERS: At what point in time? 14 MS. ZETTLER: At this point in time, 15 1985 at least. 16 A. What was your question? 17 Q. Let me ask it this way: To 18 your knowledge was synonyms agitation, insomnia, 19 and/or confusion listed under the classification 20 term depression as of November of 1985? 21 A. Insomnia was a term, you know, 22 to itself. 23 Q. How about agitation and 24 confusion? Page 444 1 A. I don't remember. 2 Q. Do you know why the event term 3 depression was used to describe this event? 4 A. Other than it says that the 5 patient had increased symptoms of depression in 6 the descriptor provided by the investigator. 7 Q. Do you know why insomnia 8 wasn't listed as an adverse event in and of 9 itself in this form? 10 A. I do not know. 11 Q. The next report is dated 12 9-25-86. Do you see that? 13 A. Yes. 14 Q. And under the descriptive 15 event it says hospitalized because of suicidal 16 ideation on 9-25-86. Daily dose of Fluoxetine 17 will be reduced. Do you see that? 18 A. Yes, I do. 19 Q. On the next page under event 20 term it lists depression; correct? 21 A. That's what it says. 22 Q. Can you tell from this form 23 whether or not this event occurred in the 24 clinical trial or was reported spontaneously? Page 445 1 MR. MYERS: Is was or was not? 2 Q. Can you tell from this form 3 whether or not this adverse event occurred in a 4 clinical trial or occurred spontaneously? 5 A. It's from a clinical trial 6 based upon the ID. 7 Q. The next report is dated 8 October 21, 1986. Do you see that? I'm going by 9 the event now. 10 A. Yes. 11 Q. This appears to be the same 12 person that was discussed in the previous report, 13 does it not? I'll make it easier. Look at the 14 manufacturing control numbers. 15 A. Okay. 16 Q. Would you agree with me that 17 it appears to be the same patient? 18 A. The ages are different. 19 Q. It's the same manufacturing 20 control number. 21 A. It is the same manufacturing 22 control number, I didn't pick that up. 23 Q. And under descriptive events, 24 at least the first paragraph on the second report Page 446 1 is the same as the previous report that we just 2 talked about; correct? 3 A. Yes. 4 Q. The second paragraph on the 5 second report states on 10-21-86, patient was 6 found in Pugit Sound, she had drowned. The 7 unofficial cause of death is probably suicide; 8 correct? 9 A. Yes. 10 Q. Can you tell from this report 11 whether or not this person was still taking 12 Fluoxetine at the time of her death? 13 A. Under section eighteen, 14 therapy dates from to, there's dashes. That 15 would indicate she had not stopped. 16 Q. Okay. So as far as you can 17 tell from this form, she was still on Fluoxetine 18 at the time she died? 19 A. Yes. 20 Q. The next report is dated 21 10-23-86; correct? 22 A. Yes. 23 Q. And under description or 24 describe event section, it states patient with Page 447 1 longstanding history of depression, took overdose 2 of Fluoxetine. She told her husband she took 3 about sixty-one twenty milligram capsules; 4 correct? 5 A. That's what it says. 6 Q. And on this form, the second 7 page, it lists three event terms, does it not? 8 A. Yes, it does. 9 Q. And one of those event terms 10 is intentional overdose; correct? 11 A. Yes. 12 Q. And it also lists somnolence 13 and depression; correct? 14 A. Yes. 15 Q. Do you know why depression is 16 listed as an adverse event term on this report? 17 A. Other than the first sentence 18 under describe event, section seven, it says 19 patient with a longstanding history of depression 20 took overdose of Fluoxetine. 21 Q. Okay. What is it about that 22 sentence that leads you to believe that that 23 sentence is why depression is listed as an 24 adverse event? Page 448 1 A. It has the word depression in 2 it. 3 Q. Under indications for use, it 4 says depression, does it not? 5 A. Yes, it does. 6 Q. And this drug is presumably 7 being tested as a treatment for depression, is it 8 not? 9 A. Yes. 10 Q. So just because it states in 11 here patient with a longstanding history of 12 depression, that doesn't mean that she had 13 increased depression on the drug, does it? 14 MR. MYERS: I object to the form only 15 because you asked her for a reason why it might 16 appear an event term, and she pointed to that. 17 MS. ZETTLER: I'm trying to explore 18 why she thinks that sentence would trigger 19 somebody to list the event term depression. 20 MR. MYERS: I object to the form. 21 A. Because as I previously state, 22 the word depression is in the sentence. 23 Q. So is it your testimony that 24 anytime the word depression appears in the Page 449 1 describe event section, it should be listed as an 2 adverse event? 3 A. No. 4 Q. Is it your testimony that 5 anytime the word depression is listed anywhere on 6 the drug experience report, it should be listed 7 as an adverse event? 8 A. Would you repeat that 9 question? 10 Q. Sure. I'm just -- I'm not 11 trying to trick you or anything, I'm just trying 12 to find out what it is about the sentence, 13 patient with longstanding history of depression 14 took overdose of Fluoxetine, that is connected in 15 your mind to the listing of depression as an 16 adverse event, why do you feel that that would be 17 a reason to list depression as an adverse event 18 on this form? 19 A. You had asked me my reason why 20 for this particular report. 21 Q. Right. 22 A. I just responded to this 23 particular report, why it could have possibly 24 been, because the word was there. I can only Page 450 1 address this report. 2 Q. Right, that's what I'm asking, 3 what it is about this sentence on this report 4 that triggers in your mind that that's why 5 depression is listed as an adverse event? 6 MR. MYERS: She answered that. 7 MS. ZETTLER: No, she didn't. 8 MR. MYERS: She did, she said because 9 it appeared in that part of the report. 10 Q. So it's your testimony that 11 simply because the word depression appears in 12 that sentence -- 13 A. For this report. 14 Q. For this report. What else is 15 there about this report that raises the issue 16 that this person was suffering from increased 17 depression or depression in your mind as an 18 adverse event? 19 A. Nothing. 20 Q. The next report is dated July 21 19, 1987; correct? 22 A. Yes. 23 Q. Under the describe event 24 section it says the patient reportedly took an Page 451 1 undetermined amount of Phenelzine in a suicidal 2 gesture. Do you see that? 3 A. Yes. 4 Q. On the second part of the 5 second page of the form, it lists intentional 6 overdose; correct? 7 A. Yes. 8 Q. And the next report dated 9 October 21, 1987 talks about a patient who was 10 admitted to the hospital with a probable manic 11 switch. He was grandiose, paranoid, and probably 12 psychotic. He told the physician that he had 13 injected Epinepherine. Do you see that? 14 A. Yes. 15 Q. It's listed as manic reaction 16 and overdose on the second page of the report; 17 correct? 18 A. Yes. 19 Q. Do you know why different 20 event terms are used on these various reports for 21 similar events meaning a report at least of an 22 intentional overdose of a drug? For instance the 23 first report lists an intentional overdose as a 24 drug overdose, the last report lists a reported Page 452 1 ingestion of a drug, self-ingestion of a drug as 2 an overdose, and the second to the last report 3 lists a reported intentional ingestion of 4 Phenelzine as in a suicide gesture as an 5 intentional overdose. I want to know what it is 6 about those three reports that similar events are 7 described with different event terms? 8 A. I don't know. 9 Q. If you could go back to the 10 report dated 10-21-86, which is about in the 11 middle of the exhibit, Pz 522 1020. Do you see 12 that? 13 A. 10-21-86? 14 Q. Right. 15 A. Yes. 16 Q. What is it about this report 17 that indicates to you that this woman suffered an 18 accidental injury, if anything? 19 A. From reading that, it said 20 patient was found in Pugit Sound, she had 21 drowned. 22 Q. Okay. It also goes on to say 23 the unofficial cause of death is probably 24 suicide, does it not? Page 453 1 A. Yes, it does. 2 Q. Would this be a situation 3 where a self-inflicted injury is listed as an 4 accidental injury? 5 A. I don't know. 6 Q. Are you aware of any situation 7 where a patient on Fluoxetine who had become 8 suicidal or violent/aggressive was rechallenged 9 with the drug to see if that was the cause of the 10 suicidality or violent/aggressive behavior? 11 A. Could you repeat that, please? 12 Q. Do you understand what it 13 means to rechallenge a patient? 14 A. Put them back on the drug. 15 Q. And it's usually done in 16 response to some sort of a reaction that a person 17 has or an event that is suffered by the person on 18 the drug to see if the drug is in fact causing 19 that event; correct, or that reaction? 20 A. Yes. 21 Q. Are you -- I'm not talking 22 necessarily about formal study, okay, but are you 23 aware of any situation where a patient who had 24 become suicidal while on Fluoxetine was Page 454 1 rechallenged on Fluoxetine to see if Fluoxetine 2 caused him or her to become suicidal? 3 A. Not that I'm aware. 4 Q. How about violent/aggressive, 5 are you aware of a situation where a patient who 6 became violent/aggressive while on Fluoxetine was 7 rechallenged with Fluoxetine to see if they 8 became violent/aggressive again? 9 A. Not that I'm aware. 10 Q. Yesterday Paul asked you a 11 bunch of questions about various types of studies 12 that had or are being or will be done about 13 Fluoxetine and suicidality. Do you remember 14 those questions? 15 (DISCUSSION OFF THE RECORD.) 16 Q. Yesterday and part of today 17 we've asked you about a number of different 18 studies that either were conducted or are being 19 conducted or are planned for the future regarding 20 Fluoxetine and suicidality. Do you recall that 21 various testimony generally? 22 A. I remember talking about the 23 different studies that had been planned while I 24 was involved with the product. Page 455 1 Q. Okay. Just to save some time 2 and not have to go through all of these 3 individual questions again about these two other 4 subjects, but are you aware of any studies 5 besides the one we talked about this morning that 6 you were aware of on agitation and the use of 7 Fluoxetine that have been performed? 8 A. No. 9 Q. Okay. How about are currently 10 being performed? 11 MR. MYERS: Agitation? 12 MS. ZETTLER: Right. 13 A. Not that I'm aware. 14 Q. How about are planned for the 15 future, in the planning stages? 16 A. I don't know. 17 Q. How about any studies that 18 have in the past been performed on 19 violent/aggressive behavior or hostility and the 20 use of Fluoxetine, are you aware of any studies 21 that in the past have been performed related to 22 that subject? 23 A. No. 24 Q. How about presently being Page 456 1 performed? 2 A. I don't know. 3 Q. Okay. Any plan for the future 4 that you know of? 5 A. I don't know. 6 Q. Have you heard of the Rocky 7 Mountain Poison Control Center study? 8 A. No. 9 Q. How about the Saskatchewan 10 data base study on self -- or destructive 11 self-behavior, I believe it is? 12 A. No. 13 Q. Self-destructive behavior. 14 A. No. 15 Q. Have you ever heard of Seamore 16 Fischer? 17 A. No. 18 Q. Do you know why patients with 19 serious suicidal risks were excluded in some of -- 20 many of the outpatient Fluoxetine studies? 21 MR. MYERS: I object to the form only 22 because I don't know that you have precisely 23 stated the exclusion criteria. I know what 24 you're getting at, but if you know, tell her. Page 457 1 Q. Are you aware that patients 2 who were considered a serious suicidal risk were 3 excluded in some or many of the outpatient 4 Fluoxetine studies? 5 A. There were exclusion criteria 6 in the protocols. 7 Q. Do you know why that was, why 8 they excluded those patients? 9 A. I do not know why. 10 Q. Have you ever heard of 11 subsyndromal syndrome? 12 A. I'm sorry, what? 13 Q. Subsyndromal syndrome. 14 A. I have heard the term, that's 15 it. 16 Q. Do you know what it is? 17 A. No. 18 Q. Where did you hear the term? 19 A. At Lilly. 20 Q. Do you remember what context 21 you heard it in? 22 A. No, I don't. 23 Q. To your knowledge were 24 Benzodiazepines used or allowed to be used in Page 458 1 protocols of testing Fluoxetine on depressed 2 patients? 3 MR. MYERS: You mean could it be a 4 concomitant medication? 5 MS. ZETTLER: Right. 6 A. Yes. 7 Q. Okay. In what situations, 8 generally or in only certain situations? 9 A. It was discussed in the 10 protocol, so whatever the different protocols 11 stated. 12 Q. Are you aware of any 13 situations, specific situation, where 14 Benzodiazepines were not allowed to be used as 15 concomitant medications in the protocols? 16 A. Not that I can recall. 17 Q. Was that ever -- was that 18 issue, the use of Benzodiazepines as concomitant 19 medications in Fluoxetine studies, ever raised as 20 an issue by the FDA, in other words was there 21 ever a concern at the FDA about the use of 22 Benzodiazepines as concomitant medicine in 23 Fluoxetine clinical trials? 24 A. I don't know. Page 459 1 Q. Are you aware of anybody at 2 Lilly who has withheld information from a 3 regulatory agency, be it the FDA or outside the 4 United States, from Lilly, anybody from Lilly? 5 A. That has -- 6 Q. Withheld any information 7 regarding Fluoxetine from the FDA or any other 8 regulatory agency? 9 A. Not to my knowledge. 10 Q. Yesterday you testified that 11 you turned over your files to various people when 12 you left your responsibilities on Fluoxetine; 13 correct? 14 A. Yes. 15 Q. Who would you have given your 16 personal notes to? 17 A. Personal notes? 18 Q. Yesterday you said you kept a 19 file on your notes, your personal notes. I'm not 20 saying personal notes as far as your personal 21 life, but I mean your own notes that you took at 22 meetings and such. 23 A. I turned over my files. I 24 didn't state I kept personal notes. Page 460 1 Q. Yesterday when Paul was asking 2 you if you took notes at meetings, you said that 3 you didn't recall specifically taking notes at 4 any given meeting, but if you had you would have 5 kept them in a file. Do you recall that 6 testimony? 7 A. I recall discussing that, I 8 didn't recall saying that I kept them all. I 9 said I would have used them and probably have 10 thrown them out when a response or whatever 11 needed was done. 12 Q. So it's your testimony now 13 that you do not have or never kept a file on 14 notes that you had taken throughout the course of 15 your employment at Lilly? 16 MR. MYERS: Like a separate file? 17 MS. ZETTLER: Right. 18 A. You mean like -- what do you 19 mean by personal notes? 20 MR. MYERS: She wants to know if you 21 kept your notes in a file. 22 Q. Right. When I say personal 23 notes, I mean notes that you have taken -- 24 A. Just my hand-scratching. Page 461 1 Q. Right. 2 A. Not particularly, no. 3 Q. Were you involved in the OUS 4 data gathering project on suicidality? 5 A. No, I was not. 6 Q. Was anybody under your 7 direction involved in that project? 8 A. I don't recall a time frame. 9 Q. If I told you it was the Fall 10 of 1990, would that help you out? 11 A. The Fall of 1990. In 12 gathering the OUS information? 13 Q. Right. 14 A. The Fall of 1990, gathering 15 the information. 16 Q. Right. 17 A. I don't think so. 18 Q. How about the U.S. data 19 gathering in preparation for Doctor Beasley's 20 article and the advisory committee meeting on the 21 issue of suicidality? 22 A. Is that the same time frame? 23 Q. I believe it's earlier in the 24 year. Page 462 1 A. At that time, I had the 2 medical writers, and I would imagine if there was 3 writing in an article, Jan Potvin would have been 4 involved working with Doctor Beasley on writing 5 it up, not data gathering. 6 Q. Do you know why Doctor 7 Hardison left Lilly? 8 A. No, I don't. 9 Q. To your knowledge did Lilly 10 employ or use in any way, or consult with any 11 outside individuals with regards to its responses 12 to the BGA questions? 13 A. Would you please repeat that? 14 Q. Sure. I'm just trying to find 15 out if Lilly used any outside consultants for any 16 reason to formulate its response to the BGA, the 17 questions that we talked about earlier. 18 A. I don't recall. 19 MS. ZETTLER: Why don't we take a 20 short break. I think I'm almost done, but I want 21 to take a look at my notes. 22 THE WITNESS: Okay. 23 (A SHORT RECESS WAS TAKEN.) 24 MS. ZETTLER: That's all I have right Page 463 1 now with the usual caveat for documents, et 2 cetera. 3 MR. MYERS: Right. Just for the 4 record, our position is that the witness has been 5 here for a couple of days, examined thoroughly, 6 and documents are produced, and our position is 7 that the deposition is over and it will not be 8 reopened absent some application and direction 9 from the court. I have no questions. 10 (THE WITNESS WAS EXCUSED.) Page 464 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 EARLENE ASHBROOK 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 6TH DAY OF 19 JANUARY, 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 465 1 2 3 E R R A T A S H E E T 4 5 COMMONWEALTH OF KENTUCKY ) : SS 6 COUNTY OF JEFFERSON ) 7 8 9 I, EARLENE ASHBROOK, THE UNDERSIGNED 10 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 11 OF MY DEPOSITION AND WITH THE CHANGES NOTED 12 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 13 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 14 THE 9TH AND 10TH DAY OF DECEMBER, 1993 AT THE 15 TIME AND PLACE STATED THEREIN. 16 PAGE NO. LINE NO. CHANGE REASON 17 PAGE NO. LINE NO. CHANGE REASON 18 19 20 21 22 23 24 _____________________________ Page 466 1 EARLENE ASHBROOK 2 3 SWORN TO AND SUBSCRIBED BEFORE ME THIS 4 _____ DAY OF __________, 1994. 5 _____________________________ NOTARY PUBLIC, STATE OF 6 KENTUCKY AT LARGE 7 8 9 10 11 Page 467 1 DIRECT EXAMINATIONBY MR. SMITH:....................5 2 CONTINUED DIRECT EXAMINATIONBY MR. SMITH:........243 3 CROSS EXAMINATIONBY MS. ZETTLER:.................306 4 COMMONWEALTH.....................................465 5 PLAINTIFFS' EXHIBIT NO. 1........................172 6 PLAINTIFFS' EXHIBIT NO. 2........................180 7 PLAINTIFFS' EXHIBIT NO. 3........................186 8 PLAINTIFFS' EXHIBIT NO. 4........................196 9 PLAINTIFFS' EXHIBIT NO. 5........................287 10 PLAINTIFFS' EXHIBIT NO. 6........................303 11 PLAINTIFFS' EXHIBIT NO. 7........................328 12 PLAINTIFFS' EXHIBIT NO. 8........................331 13 PLAINTIFFS' EXHIBIT NO. 9........................353 14 PLAINTIFFS' EXHIBIT NO. 10.......................358 15 PLAINTIFFS' EXHIBIT NO. 11.......................366 16 PLAINTIFFS' EXHIBIT NO. 12.......................384 17 PLAINTIFFS' EXHIBIT NO. 13.......................391 18 PLAINTIFFS' EXHIBIT NO. 14.......................409 19 PLAINTIFFS' EXHIBIT NO. 15.......................425 20 PLAINTIFFS' EXHIBIT NO. 16.......................441 21 COMMONWEALTH.....................................466 Page 468