SUPERIOR COURT OF THE STATE OF CALIFORNIA FOR THE COUNTY OF LOS ANGELES DR. MARIUS SAINES, etc., et al., ) Case No: ) SC 008331 Plaintiffs, ) ) vs. ) ) ELI LILLY & COMPANY, a corporation;) DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1-) 100, inclusive, ) ) Defendants. ) ___________________________________) The deposition upon oral examination of LAURA A. FLUDZINSKI, a witness produced and sworn before me, Linda M. Bour, a Notary Public in and for the County of Marion, State of Indiana, taken at the offices of Baker & Daniels, 300 North Meridian Street, Suite 2700, Indianapolis, Marion County, Indiana, on the 28th day of October 1993, pursuant to notice in accordance with the applicable Civil Rules of Procedure. BOUR REPORTING P.O. Box 78261 Indianapolis, IN 46278-0261 (317) 875-3914 PAGE 1 1 A P P E A R A N C E S 2 NANCY ZETTLER COUNSEL FOR GROUP OF PLAINTIFFS 3 LEONARD M. RING AND ASSOCIATES, P.C. 111 WEST WASHINGTON AVENUE, SUITE 1333 4 CHICAGO, ILLINOIS 60602 5 LAWRENCE J. MYERS COUNSEL FOR ELI LILLY AND COMPANY 6 FREEMAN & HAWKINS 4000 ONE PEACHTREE CENTER 7 303 PEACHTREE STREET, N.E. ATLANTA, GEORGIA 30308-3243 8 MARGARET M. HUFF 9 ELI LILLY AND COMPANY LILLY CORPORATE CENTER 10 307 EAST McCARTY STREET INDIANAPOLIS, IN 46285 11 MIRA DJORDJIC STEWART 12 COUNSEL FOR RESPONDENT, MICHAEL DENSON, M.D. CLAUSEN MILLER GORMAN CAFFREY & WITOUS 13 10 SOUTH LaSALLE CHICAGO, ILLINOIS 60603 PAGE 2 1 I N D E X O F E X A M I N A T I O N 2 PAGES 3 DIRECT EXAMINATION....................... 4 Questions by Ms. Nancy Zettler 4 5 I N D E X O F E X H I B I T S 6 PAGES 7 Deposition Exhibit No.: 8 EXHIBIT 01............................... 97 9 EXHIBIT 02............................... 100 EXHIBIT 03............................... 104 10 EXHIBIT 04............................... 107 EXHIBIT 05............................... 109 11 EXHIBIT 06............................... 111 12 EXHIBIT 07............................... 116 EXHIBIT 08............................... 118 13 EXHIBIT 09............................... 120 EXHIBIT 10............................... 121 14 EXHIBIT 11............................... 124 15 EXHIBIT 12............................... 131 EXHIBIT 13............................... 137 16 EXHIBIT 14............................... 138 EXHIBIT 15............................... 139 17 EXHIBIT 16............................... 140 18 EXHIBIT 17............................... 142 EXHIBIT 18............................... 152 19 EXHIBIT 19............................... 153 EXHIBIT 20............................... 154 20 EXHIBIT 21............................... 156 21 EXHIBIT 22............................... 158 EXHIBIT 23............................... 161 22 EXHIBIT 24............................... 163 EXHIBIT 25............................... 168 23 EXHIBIT 26............................... 169 24 EXHIBIT 27............................... 170 EXHIBIT 28............................... 172 PAGE 3 1 L A U R A A. F L U D Z I N S K I, having 2 been first duly sworn to tell the 3 truth, the whole truth and nothing but 4 the truth relating to said matter, was 5 examined and testified as follows: 6 DIRECT EXAMINATION, 7 QUESTIONS BY NANCY ZETTLER: 8 Q Could you please state your full name for 9 the record. 10 A Laura Ann Fludzinski. 11 Q Would you like to be called Mrs., Ms.; does 12 it matter? 13 A Doesn't matter. 14 Q Miss Fludzinski, have you ever given a 15 deposition before? 16 A No. 17 Q Let me give you some of the ground rules 18 just mostly to make it easiest on the court 19 reporter and so we make sure we understand 20 each other, okay? 21 A Okay. 22 Q I've got a little bit of a cold, so if you 23 can't understand what I'm saying or my 24 voice drops out or if I just can't talk for PAGE 4 1 a second, let me know and I'll just 2 rephrase my question so you understand it, 3 okay? 4 A Okay. 5 Q If you answer the question, I'm going to 6 assume that you answered it as asked; is 7 that fair? 8 A Yes. 9 Q Any time you want to take a break, feel 10 free to tell Larry or me or anybody and 11 we'll take a break, okay? 12 A Thank you. 13 Q You've been doing a good job of it so far, 14 but you have to make all of your answers 15 verbal, say yes, no. You can't go uh-huh 16 or uh-uh and shake your head because she 17 can't take that down. 18 A Okay. 19 Q And we have to try to allow each other to 20 complete my question or your answer so she 21 can take that down, also, okay? 22 A Yes. 23 Q Can you give me your date of birth? 24 A April 13th, 1958. PAGE 5 1 Q And your Social Security number? 2 A XXXXXXXXXX. 3 Q And your current address? 4 A XXXXXXXX. 5 Q You're going to have to spell that. 6 A XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 7 XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 8 XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 9 XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. 10 Q How long have you lived there? 11 A Nearly three years. 12 Q Please excuse my sniffling and everything. 13 MR. MYERS: I've warned her. 14 MS. ZETTLER: Okay, good. 15 Q Do you have any plans on moving in the near 16 future? 17 A No, I do not. 18 Q You're married; right? 19 A Yes. 20 Q Do you have any children? 21 A No. 22 Q And what is your husband's name? 23 A XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX. 24 Q Could you give me a brief description of PAGE 6 1 your education past high school, after high 2 school. 3 A I attended the University of Cincinnati. I 4 have a Bachelor of Science Degree. I 5 graduated from there in 1980. 6 Q 1980? 7 A Yes. 8 Q Anything else? 9 A I've taken a few additional courses, but 10 they have not led to any advanced degree. 11 Q What did you get your Bachelor's in? 12 A Biology. 13 Q And what additional courses did you take? 14 A Some additional biochemistry classes, an 15 anatomy and physiology class, some 16 environmental toxicology classes. 17 Q Anything else? 18 A A statistics course. 19 Q Anything else? 20 A That's all that I remember. 21 Q And where did you take these additional 22 courses? 23 A At the University of Cincinnati and here in 24 Indianapolis at IUPUI. PAGE 7 1 Q And what's IUPUI? 2 A Indiana University-Purdue University in 3 Indianapolis. 4 Q Any of those extra courses that you took, 5 were those at the request of Eli Lilly? 6 A No. 7 Q Can you give me a general breakdown of what 8 your work history has been before Lilly? 9 You can exclude things like waitressing 10 jobs in college and things of that nature. 11 A When I graduated from the University of 12 Cincinnati, I took a position as a research 13 assistant in one of the medical school 14 research laboratories; it was the 15 Department of Pharmacology and Cell 16 Biophysics. 17 Q I'm sorry, and what? 18 A Cell Biophysics. I worked there for nearly 19 three years. The Ph.D. that I was working 20 with moved his research laboratory from the 21 University of Cincinnati to Ohio State 22 Medical School. I went with him for about 23 a three-month period to start up his new 24 laboratory at Ohio State, hire additional PAGE 8 1 staff and train them, and then I joined Eli 2 Lilly & Company. 3 Q When did you start as a research assistant 4 in the Department of Pharmacology at the 5 University of Cincinnati? 6 A I actually started in the quarter of school 7 before I graduated, so it would have been 8 the spring of 1980. 9 Q To approximately the spring of '83? 10 A Yes. It was more the fall, like September 11 time frame of '83 on. 12 Q And then you worked for three months 13 with -- who was the Ph.D. you worked with? 14 A His name was David Johnson. 15 Q And then you worked with him for three 16 months at Ohio State? 17 A Yes. 18 Q So you came to Lilly in spring of '84? 19 A January of '84. 20 Q What did you do as a research assistant at 21 the University of Cincinnati? 22 A We looked at the way that skeletal and 23 smooth muscle work at the cellular level. 24 Q Did you do any drug testing while you were PAGE 9 1 there? 2 A Some. 3 Q What types of drugs did you work on? 4 A The calcium channel blockers. 5 Q Any psychotropic drugs? 6 A No. 7 Q Did you work on any clinical trials? 8 A No. 9 Q How about when you went to help Dr. Johnson 10 set up his lab at Ohio State, did you do 11 any drug testing or clinical trial drug 12 work there? 13 A Drug testing, but no clinical trial work. 14 Q What types of drugs did you work on there? 15 A The same, the calcium antagonists. 16 Q Prior to joining Lilly in January of 1984, 17 did you have any experience whatsoever 18 regarding -- and I don't mean consuming -- 19 but regarding psychotropic drugs? 20 A No. 21 Q How did you find out about a position at 22 Lilly? 23 A I sent my resume' to a number of 24 pharmaceutical companies and received a PAGE 10 1 response from Lilly asking me to come and 2 speak with some of their research 3 scientists. 4 Q That was here in Indianapolis? 5 A Yes. 6 Q And did you do so? 7 A Yes. 8 Q Who did you speak with? 9 A A number of individuals. One name I can 10 recall is Marlene Cohen because she became 11 my new boss. 12 Q Can you recall any other names of the 13 people you spoke with? 14 A No. 15 Q Is Marlene Cohen still at Lilly? 16 A Yes. 17 Q Is she working with Fluoxetine? 18 A I don't know. 19 Q Has she ever worked with Fluoxetine? 20 A I don't know. 21 Q What position did you first hold at Lilly 22 when you started in January of '84? 23 A A research associate. 24 Q And how long were you a research associate? PAGE 11 1 A Until approximately October 1987. 2 Q And what does a research associate do? 3 A Conducts scientific experiments in a 4 research lab. 5 Q Did any of your work as a research 6 associate deal with Fluoxetine? 7 A No. 8 Q Have you worked for Lilly consistently from 9 January of '84 to the present? 10 A Yes. 11 Q What was the next position you held at 12 Lilly? 13 A Clinical Research Administrator in the 14 Medical Department. 15 Q And how long were you a CRA? 16 A For approximately two years. 17 Q So the fall of '89? 18 A Yes. 19 Q And what did you do as a CRA? 20 A I worked on Fluoxetine clinical trials. 21 Q Exclusively? 22 A Yes. 23 Q Were these normal CRA duties working with 24 the clinical investigators making sure the PAGE 12 1 data they sent in was correct and things of 2 that nature? 3 A Yes. 4 Q Any unusual projects that you worked on 5 regarding Fluoxetine while you were a CRA? 6 MR. MYERS: Unusual? 7 Q Anything out of the ordinary for a CRA? 8 A No. 9 Q What position did you hold after that at 10 Lilly? 11 A Department Head. 12 Q Which department? 13 A It started out as -- I think it was called 14 Clinical Neurosciences, and it involved all 15 of the CNS compounds that Lilly had in 16 clinical trial development. Later the 17 Fluoxetine group was specifically formed 18 into a separate group and I became the 19 department head of that group. 20 Q And what was that group called? 21 A I don't remember its official title. 22 Q Medical Plans, does that sound familiar? 23 A Medical Plans is the reference name for the 24 entire division of CRAs that work at Lilly PAGE 13 1 on clinical trials for all compounds. 2 Q When did they create the separate group for 3 Fluoxetine? 4 A I don't remember the exact date. 5 Q Can you give me a year? 6 A I can't be specific. 7 Q And you became a department head in the 8 fall of '89? 9 A Yes. 10 Q How long were you a department head? 11 A Nearly two years. 12 Q So summer of '91? 13 A No, I take that back. I apologize. It 14 must have been one year because at the end 15 of 1990 I went to my new responsibilities 16 in Europe. 17 Q And what are your responsibilities now? 18 A In Europe? 19 Q Yes. 20 A My title is Clinical -- Manager for 21 European Clinical Research Administration. 22 Q Clinical Manager for European Clinical 23 Research Administration? 24 A Manager for European Clinical Research PAGE 14 1 Administration. 2 Q Okay. 3 A We have medical offices in most of the 4 major countries in Europe where we work 5 with local investigators to conduct 6 clinical trials. And the group at Erl Wood 7 under my responsibility coordinates the 8 activity for Lilly amongst all those 9 countries. 10 Q So you're at the Erl Wood office? 11 A Yes. 12 Q Has that been your position since you've 13 gone to England? 14 A Yes. 15 Q Give me an idea of some of your 16 responsibilities in that position. 17 A The job has changed over the three years 18 that I've been there. 19 Q Okay. What was it like when you first 20 started, what did you do? 21 A The work that I described, the medical 22 departments that we have in most of the 23 major countries in Europe, they would work 24 with their investigators who treated PAGE 15 1 patients, and the case report forms, the 2 data, would come from those countries into 3 the Erl Wood office where they would be 4 entered into a computer. The group that 5 worked under me would be responsible for 6 the CRA responsibilities that you described 7 earlier, the review and editing of those 8 cases, following up on errors or blank 9 spaces in those case report forms. 10 We had a group of statisticians 11 within the group and a group of systems 12 analysts that would review and analyze the 13 data at the end of those clinical trials. 14 And then we had a group of physicians who 15 would work with the statisticians and with 16 the CRAs to write reports from that data. 17 My responsibility was to coordinate and 18 facilitate those people doing that work. 19 Q And how has that changed? 20 A During the time that I've been there, our 21 group has reorganized and downsized quite 22 extensively. The data collection and 23 editing that I described to you has been 24 moved into each of those country offices PAGE 16 1 and so those medical folks that sit there 2 are now responsible for that aspect of the 3 work. My group now is involved in 4 training, quality control, statistical 5 support and systems support, but not 6 directly in those clinical trials. 7 Q What do you mean when you say "not directly 8 in those clinical trials"? 9 A They're not involved in the day-to-day 10 collection or monitoring or editing of 11 those data but more in the training of the 12 staff who are. 13 Q When did the reorganization take place? 14 A It started in January of last year and is 15 continuing as we speak. 16 Q Do you have any responsibilities with 17 regards to Fluoxetine at this time? 18 A No. 19 Q When did your responsibilities with regards 20 to Fluoxetine cease? 21 A My direct involvement with Fluoxetine 22 ceased when I left to take my role in the 23 UK. 24 Q Have you had any responsibilities with PAGE 17 1 regards to Fluoxetine since you've gone to 2 the UK? 3 A While I have been in my position as 4 manager, there were Fluoxetine clinical 5 trials ongoing. Those have since been 6 completed and I -- my responsibility 7 towards them would have been the 8 coordination of the activities of other 9 people working directly on them. I was not 10 directly involved. 11 Q Okay. Just make sure I'm not confused. 12 You went to Europe at the end of 1990; 13 correct? 14 A Yes. 15 Q Was your sole responsibility as a CRA 16 Fluoxetine? 17 A Yes. 18 Q And how about when you were a department 19 head? I take it when the group split off, 20 the Fluoxetine group split off, your sole 21 responsibility was Fluoxetine at that time? 22 A Yes. 23 Q How about prior to that as a department 24 head, Clinical Neurosciences? PAGE 18 1 A There were a number of compounds including 2 Fluoxetine in that group. 3 Q So from October of '87 through the fall of 4 '89, your sole responsibility was 5 Fluoxetine; correct? 6 A Yes. 7 Q And then you had responsibility for 8 Fluoxetine as well as other compounds from 9 the fall of '89 to whenever the Fluoxetine 10 group was created? 11 A Yes. 12 Q And from when the Fluoxetine group was 13 created until the end of 1990 when you went 14 to Erl Wood, you again had sole -- your 15 sole responsibility was related to 16 Fluoxetine? 17 A Yes. 18 Q What did you do in preparation for your 19 deposition today? 20 A I had a meeting with Mary and another 21 attorney on Tuesday afternoon and spoke 22 briefly with Larry this morning. 23 Q Who was the other attorney? 24 A Steve Lore (phonetic) or Lore. PAGE 19 1 MR. MYERS: Lore. 2 Q How long did you meet with Mary and Steve 3 Lore? 4 A For approximately three hours. 5 Q Were you shown any documents? 6 A No. 7 Q Have you reviewed any documents in 8 preparation for your deposition? 9 A No, I have not. 10 Q Have you asked to see documents? 11 A No, I have not. 12 Q When were you first contacted about giving 13 a deposition? 14 A Mary sent me an electronic mail message in 15 August asking when was the next time that I 16 would be in the U.S. for business purposes. 17 At that time I didn't know. 18 Q When in August, do you remember? 19 A No, not the exact date. 20 Q Was it the beginning or the end of the 21 month? 22 A I'll say the middle. 23 Q Okay. Did she ask you at that time to come 24 to Indianapolis to give your deposition? PAGE 20 1 A No. 2 Q When was the next time you were contacted 3 about the deposition? 4 A When I learned that I would be traveling to 5 Indianapolis on a business trip, I informed 6 Mary that I would be here. 7 Q When did you learn you would be here? 8 A Approximately four weeks ago. 9 Q How long have you been here? 10 A I arrived Saturday a week ago. I don't 11 remember. Is that the 16th or 17th? I 12 can't really remember the date unless you 13 put a calendar in front of me. 14 Q Okay, me neither. When are you planning on 15 leaving? 16 A This Saturday, the 30th. 17 Q And why are you here? 18 A My job has recently changed a bit. In 19 addition to the medical responsibilities 20 which I described to you earlier, I also 21 now have responsibility for the Medical 22 Systems Support in Europe which is closely 23 aligned with the U.S. systems organization 24 which has just undergone a reorganization, PAGE 21 1 so the purpose of my trip in these two 2 weeks was to meet with my new boss and 3 other individuals within the systems 4 community to learn more about what they do 5 and how I would interact with them in my 6 new responsibilities. 7 Q Did Mary or anybody else ask you to set 8 aside more than one day for your 9 deposition? 10 A No. 11 Q Would you have been able to set aside more 12 than one day? 13 A No. 14 Q Why not? 15 A The purpose of my trip was really 16 business-related and it's been very 17 difficult to fit in all the folks that I do 18 need to talk to and carve out a day for 19 this. 20 Q Would it have been possible for you to stay 21 for another couple of days? 22 A No, it would not. 23 Q Why not? 24 A Because of my responsibilities waiting for PAGE 22 1 me in the UK. 2 Q What is pressing that couldn't wait another 3 day? 4 A I have approximately 25 people that report 5 directly to me. 6 Q Who has been covering for you while you are 7 gone? 8 A My boss. 9 Q Your boss couldn't cover for you for a 10 couple more days? 11 A I think it's asking quite a bit of him at 12 the moment to cover for me now. 13 Q Why? 14 A Because he has other responsibilities as 15 well. 16 Q Regardless, you were not asked to set aside 17 more than one day for your deposition? 18 A No. 19 Q What is Medical Systems Support or what is 20 Medical Systems? 21 A It's the group of systems analysts who 22 support the computer needs of the medical 23 department. 24 Q What are some of those medical needs, what PAGE 23 1 are those needs? 2 A They create data entry systems to capture 3 clinical trial data; they create reports to 4 extract that data once it's into the 5 computer. 6 Q Anything else? 7 A No. 8 Q When you say "create reports", what do you 9 mean, what reports? 10 A In order to write up final reports or 11 manuscripts of the data you need to 12 condense it somehow into listings or 13 spreadsheets or whatnot, and they are the 14 group that prepares that. 15 Q Oh, okay. So when you say reports, you 16 mean they analyze the data, set it up in a 17 form that's appropriate for the reports? 18 A Yes. They would not do an analysis. We 19 have a statistical component that does 20 that. 21 Q They just make it look nice, is that what 22 you mean? 23 A I don't know if that's the terminology that 24 I would use. PAGE 24 1 Q I'm just confused by your term report. 2 A On a case report form you collect many, 3 many data points from many, many patients 4 and the systems people will pull all of 5 that together in listings, not a narrative 6 report, but basically data output. 7 Q Okay. So it's a result of queries? They 8 ask for -- you ask for everybody's Hamilton 9 Depression rating scale total score for 10 certain visits? 11 A Yes. They give us a listing of all that, 12 yes. 13 Q And what is your role going to be with the 14 systems support? 15 A We have systems support in each of the 16 countries that we work with in Europe, so 17 it will be coordinating that group of 18 individuals who all sit in different 19 places. 20 Q Does each affiliate have their own support? 21 A The larger countries do; the smaller 22 countries share resources. 23 Q Let's go back to when you were a CRA. How 24 did you first become involved with PAGE 25 1 Fluoxetine working on Fluoxetine? 2 A When I joined the medical department, I 3 began working on an obesity clinical trial. 4 Q Any others? 5 A Also while I was a CRA, I worked on other 6 indications for Fluoxetine. Bulimia is one 7 of those; smoking cessation is another. 8 Q Any depression trials? 9 A No. 10 Q Did you have any responsibilities with 11 regards to Fluoxetine in the treatment of 12 depression whatsoever? 13 A Not as a CRA. 14 Q What type of work did you do on the 15 obesity, bulimia and smoking cessation 16 trials? 17 A The CRA work that you described earlier, 18 working with investigators, reviewing their 19 case report forms. 20 Q Did you fill out adverse event reports on 21 adverse events that occurred during the 22 clinical trials? 23 A Yes, I did. 24 Q You're familiar I take it with the FDA's PAGE 26 1 definition of a serious adverse event; 2 correct? 3 A Yes. 4 Q Tell me what you would do with regards to a 5 serious adverse event that would occur 6 during a clinical trial. 7 A The investigators were instructed to call 8 us on the phone when a serious adverse 9 event meeting those criteria occurred. We 10 had a work sheet that we would use, so I 11 would take out that work sheet and over the 12 telephone would just work through the 13 work sheet asking the investigator the 14 questions necessary to fill in the 15 work sheet. 16 I would pass it to the clinical 17 physicians at Lilly that I worked with who 18 would review it. It then went to our Drug 19 Epidemiology Unit where it was entered into 20 the DEN system. We would then receive the 21 printout of what was in the DEN system with 22 the work sheet to review for accuracy and 23 completeness. I would look at it, and then 24 it would go back to the clinical research PAGE 27 1 physician who would also review it and then 2 sign it. 3 Q And when you say the printout, you mean the 4 1639? 5 A Yes. 6 Q What would happen with the 1639 after the 7 physician signs it? 8 A In the medical department it was kept in 9 two places. There was a copy in the 10 patient file itself with other copies of 11 the case report form. We also then had a 12 central file for each protocol, so you 13 would have all the 1639s in a binder that 14 occurred for a given study. They were also 15 submitted to the FDA, but that was not from 16 within the medical department; that was 17 from the regulatory department. 18 Q But it's your understanding that the 1639s 19 that resulted from serious clinical trial 20 adverse events were reported to the FDA on 21 1639s? 22 A Yes. 23 Q Would you assign any expectancy or make any 24 judgments regarding adverse events when you PAGE 28 1 were filling out the form? 2 A No. 3 Q Who would do that? 4 A To my knowledge no one because the FDA does 5 not assess causality. They want all 6 reports meeting criteria for serious. 7 Q But as far as just for in-house at Lilly, 8 did anybody try to make a determination as 9 to whether or not an adverse event was 10 causally related to the study drugs? 11 A Not that I'm aware of. 12 Q How about expectancy, who would assign 13 expectancy? 14 A Expectancy is also I believe in the 15 legislation, the Code of Federal 16 Regulations. If it has happened 17 previously, it's expected. If it's a new 18 report, it's unexpected. 19 Q So let's take for instance suicide, okay? 20 So if you had seen suicides previously in 21 clinical trials, then this would be 22 expected? 23 A By that definition, but it would also meet 24 criteria for serious in the investigator's PAGE 29 1 opinion. 2 Q What impact does a determination that an 3 adverse event is unexpected have in the 4 reporting process if any? 5 A In the regulatory component if an adverse 6 event meets criteria for serious and is 7 unexpected, it would fall within the 8 guidelines of reporting that information to 9 the FDA within their 3-day alert 10 guidelines. 11 Q And what if it was expected? 12 A I can't quote you the regulatory law, but 13 then it would fall outside of that 3-day 14 window, but within a 10-day or 30-day 15 window I believe. 16 Q It would still be reported to the FDA; it 17 would just be reported later than the three 18 days? 19 A Yes. 20 Q How about a non-serious clinical trial 21 adverse event? Can you tell me about -- is 22 there a difference in the procedure that 23 you would follow if a non-serious clinical 24 trial adverse event was reported to you? PAGE 30 1 A Non-serious events would have been 2 collected within the case report form 3 itself. There is a field to capture 4 adverse event information. 5 Q Would a 1639 be filled out? 6 A No. 7 Q What would happen with the information in 8 the case report form regarding that 9 non-serious adverse event? 10 A It would go into the clinical trial 11 database. And at the time that the study 12 was unblinded, treatment groups assigned 13 and analyses performed and the final 14 reports written up, it would fall into the 15 category of the safety analyses for that 16 particular study and would be reviewed. 17 Q It's my understanding from previous 18 depositions that the serious clinical trial 19 adverse event data was stored in the DEN 20 computer. 21 A Yes. 22 Q And that the non-serious clinical trial 23 adverse event data was stored in the 24 clinical trial database. PAGE 31 1 A Yes, but the serious adverse event data 2 that you described being in the DEN 3 database is also in the clinical trial 4 database. 5 Q Okay. Is there a separate database for 6 clinical trial adverse events or is that 7 information contained in the total clinical 8 trial database? 9 A It's in the total clinical trial database. 10 There aren't separate files. There is one 11 more point of review I'd like to add. 12 Q Sure. 13 A We call these morning reports and each 14 physician working on a study is given a 15 printout of all the adverse events that 16 have been entered into the clinical trial 17 system from the day before each morning so 18 that even if they don't meet the criteria 19 for serious, they are reviewed on a daily 20 basis. 21 Q So the morning reports would be given to 22 the clinical research physicians working on 23 the specific clinical trial? 24 A Yes. And if that physician is not PAGE 32 1 available for some reason, it would be 2 passed to a colleague for review. 3 Q What was the purpose of reviewing the 4 morning reports? 5 A For the physician to stay on top of any 6 safety issues in clinical trials. 7 Q What would be done by the physician in 8 response to a serious clinical trial 9 adverse event that was reported in the 10 morning reports, if anything? 11 A One of the notations on the morning report, 12 if the report meets criteria for serious, 13 it would note whether a 1639 has been filed 14 or not, so it would be like a double or 15 triple check in the system to ensure that 16 the report had been put into DEN. 17 If there were other adverse events 18 for which the physician wanted more 19 information, they would come to the CRA and 20 ask to see the case report forms themselves 21 or the physician would call the 22 investigator in the field and they would 23 have a dialogue about the patient. 24 Q Did you have any responsibilities with PAGE 33 1 regards to follow-ups on any clinical trial 2 adverse events? 3 A Only in terms of seeking additional 4 information to complete the forms. Any 5 clinical discussion would have been held 6 between the investigator and the research 7 physician at Lilly. 8 Q Did you have responsibilities for assigning 9 adverse event terms to the various 10 occurrences? 11 A Yes. 12 Q During the time that you were a CRA, did 13 you use the COSTART or the ELECT dictionary 14 or another dictionary? 15 A We used the -- I believe ELECT initially 16 was a subset of the COSTART dictionary, and 17 then Lilly adopted the COSTART dictionary 18 during the time that I was a CRA. 19 Q What do you mean when you say it was a 20 subset of the COSTART dictionary? 21 A At the time that we initially adopted it, 22 the FDA to my knowledge hadn't fully 23 adopted the COSTART dictionary, and so we 24 used what was available, and then as the PAGE 34 1 FDA made their position more clear, we 2 adopted their dictionary. 3 Q When did you first adopt the ELECT 4 dictionary? 5 A I don't remember. 6 Q Was it before or after you became a CRA? 7 A Before. 8 Q How did you know that the ELECT dictionary 9 was adopted? Strike that. Is it your 10 understanding that the ELECT dictionary is 11 a dictionary created by an entity outside 12 of Lilly? 13 A I don't know. 14 Q Do you know what ELECT stands for? 15 A Eli Lilly Event Classification Terms. 16 Q Where did you get your information that the 17 FDA had not adopted or fully adopted the 18 COSTART when the ELECT dictionary came into 19 use at Lilly? 20 A As a CRA I remember discussions about the 21 dictionary. 22 Q Which one, COSTART or ELECT? 23 A The dictionary in general. I mean, it was 24 a tool that we used every day. PAGE 35 1 Q Did you have a hard copy of that, of the 2 dictionary that you used or did you use it 3 on the computer? 4 A Both. 5 Q Did you state earlier that eventually Lilly 6 adopted the COSTART dictionary? 7 A I'm sorry, what was your question? 8 Q Was it your testimony -- I just want to 9 make sure I heard you correctly earlier. 10 Did you testify earlier that eventually 11 Lilly adopted the COSTART dictionary once 12 the FDA finalized their position? 13 A Yes. 14 Q Do you remember when that happened? 15 A No. 16 Q Was that before or after you went to 17 Europe? 18 A Before. 19 Q Do you use an event dictionary over in Erl 20 Wood? 21 A Not now. When I first arrived and my group 22 was involved in clinical trial work, yes. 23 Q What dictionary did you use then? 24 A The same one that was used in Indianapolis. PAGE 36 1 Q So if it was COSTART, you were using 2 COSTART in Europe? 3 A Uh-huh. 4 Q You have to say yes or no. 5 A Yes. I'm sorry. 6 Q You're doing fine. Don't worry. 7 MS. ZETTLER: Can we take a 8 break? 9 MR. MYERS: Sure. 10 (A brief recess was taken.) 11 Q Does your husband work for Lilly? 12 A Yes. 13 Q What does he do? 14 A He's the Managing Director of the Lilly 15 Research facility at Erl Wood. 16 Q I take it you were both transferred at the 17 same time? 18 A Yes. 19 Q What did he do at Lilly prior to the 20 transfer? 21 A He joined the company as an organic chemist 22 in the research laboratories. He's had a 23 number of assignments since then. He was 24 in a financial position for a time, in a PAGE 37 1 project management role for a time, and 2 then in his position at Erl Wood. 3 Q Did he ever work on Fluoxetine? 4 A No. 5 Q All right. Earlier you said when you were 6 a CRA, you worked on obesity, bulimia and 7 smoking trials; correct? 8 A Yes. 9 Q How many obesity trials did you work on? 10 A I was responsible for two. 11 Q How about bulimia, how many bulimia trials? 12 A One. 13 Q How about the smoking? 14 A One. 15 Q In any of those four trials during the 16 period of time that you were a CRA, did 17 anybody die? 18 A I don't remember. 19 Q During any of those trials while you were a 20 CRA, did anybody attempt to commit suicide? 21 A I don't remember. 22 Q If somebody died on a trial, what was the 23 procedure at Lilly? 24 A The serious adverse events procedure that PAGE 38 1 we discussed earlier, the investigator 2 would call Lilly -- either the CRA or the 3 research physician -- and report it. 4 Q And that would have to be reported to the 5 FDA within three days; correct? 6 A (Affirmative nod). 7 MR. MYERS: Yes? 8 A Yes, sorry. 9 Q Okay. Were there any other CRAs working 10 with you on these trials when you were 11 working on them? 12 A No. 13 Q In your job as a department head, what were 14 your responsibilities with regards to 15 Fluoxetine? Start with your general 16 responsibilities. 17 A There were a number of CRAs and other staff 18 who were working directly on the clinical 19 trials. My responsibilities were to 20 coordinate their activities, facilitate 21 problem-solving discussions, planning 22 meetings. 23 Q Did you work directly on any projects 24 related to Fluoxetine? PAGE 39 1 A As a department head? 2 Q Right. 3 A Describe projects. 4 Q Anything that you worked on personally 5 yourself as opposed to coordinating or 6 administrating in your position as a 7 department head. 8 A There were some final research reports 9 being written at the time on some of the 10 obesity studies and on one of the bulimia 11 studies, and I participated in some of that 12 writing effort. 13 Q Anything else? 14 A No. 15 Q Did you ever work with Dr. Paul Stark? 16 A No. 17 Q How about Dr. Wernicke? 18 A Yes. 19 Q What was your involvement with 20 Dr. Wernicke? 21 A Dr. Wernicke was one of the psychiatrists 22 in the group when I was a CRA. 23 Q So he would be the clinical research 24 physician on a trial that you were working PAGE 40 1 on? 2 A Not directly. His responsibilities were 3 more on the depression trials, but on 4 occasion when my research physician was out 5 of the office for one reason or another, he 6 would be the person who reviewed the 1639 7 reports, for instance, that I filled out. 8 Q Who was the research physician that you 9 worked with? 10 A Louise Levine. 11 Q Did you work with any other research 12 physicians as a direct, you know, everyday 13 kind of job? 14 A No. 15 Q Have you worked with Dr. David Wheadon? 16 A Yes. 17 Q In what capacity did you work with 18 Dr. Wheadon? 19 A Again, when I was a department head, he was 20 one of the psychiatrists. 21 Q So it was similar to Dr. Wernicke, he would 22 fill in if Dr. Levine was unavailable? 23 A Yes, and also in my department head role 24 Dr. Wheadon was working on trials primarily PAGE 41 1 at the time in the area of 2 obsessive-compulsive disorder and so the 3 CRAs that I was responsible for would have 4 been working directly with him. 5 Q You worked on the international data 6 gathering project for suicidality; correct? 7 A Yes. 8 Q Did you work with Dr. Wheadon on that 9 project? 10 A He was involved. 11 Q Any other suicidality-related projects that 12 you worked with Dr. Wheadon? 13 A No. 14 Q How about violent aggressive behavior 15 projects, did you work on any of those with 16 Dr. Wheadon? 17 A I don't remember. 18 Q How about Dr. Dorothy Dobbs? 19 A Don't know. 20 Q Don't know her? 21 A I don't know her. 22 Q Why don't you list for me the projects that 23 you worked on related to Fluoxetine and 24 suicidality. PAGE 42 1 A You described or you mentioned the 2 international data gathering exercise. 3 Related to that was a review of the U.S. 4 clinical trial database. As a department 5 head, that was probably my main area of 6 focus, was coordinating all of the 7 activities amongst the group that reported 8 to me and associated groups like the 9 systems support group, the statistician 10 group, et cetera, in doing that work. 11 Q Any other projects besides the 12 international data gathering project and 13 the review of the U.S. clinical trial 14 database? 15 MR. MYERS: With respect to 16 suicidality? 17 MS. ZETTLER: Right. 18 A Both of those efforts led to preparation of 19 the manuscript and also preparation for a 20 meeting with the FDA. I participated in 21 the preparation for the meeting with the 22 FDA, but the manuscript work was still 23 ongoing when I left for my job in the UK, 24 so it was not completed until after I was PAGE 43 1 already in England. 2 Q When you say the preparation of the 3 manuscript, are you talking about 4 Dr. Beasley's meta-analysis article? 5 A Yes. 6 Q Were you a co-author on that? 7 A No. 8 Q Have you been a co-author on any articles 9 published on Fluoxetine by Lilly? 10 A Yes. 11 Q What articles? 12 A I don't recall the titles, but they were 13 related to the obesity indication and they 14 were published in the Journal of Obesity. 15 Q When you say preparation -- strike that. 16 When you say you were involved in 17 preparation for the meeting with the FDA, 18 are you talking about the advisory 19 committee meeting in September of '91? 20 A Yes. Wait, there were two meetings with 21 the FDA. One happened when I was still 22 here and one happened after I left -- not 23 the one in '91, the one previous to that -- 24 and I believe that was in September of PAGE 44 1 1990. 2 Q '90, okay. Were you involved in 3 preparations for the advisory committee 4 meeting? 5 MR. MYERS: The September '91 6 meeting? 7 MS. ZETTLER: Correct. 8 A No. 9 Q You in fact attended the meeting with the 10 FDA in September of '90; correct? 11 A Yes. 12 Q What was your role at that meeting? 13 A I had with me hard copies of the 14 presentation materials, the acetates that 15 we were going to use and basically sat on 16 the sidelines as a reference person/ 17 resource person, but was not called upon to 18 make any comment or was not involved other 19 than sitting on the side of the room and 20 listening to what was going on. 21 Q Did you take notes during the meeting? 22 A No, I did not. 23 Q Do you know if anybody took notes during 24 the meeting? PAGE 45 1 A I don't recall. 2 Q Have you ever seen meeting minutes that 3 resulted from the meeting? 4 A No, I did not. 5 Q How about with regards to violent 6 aggressive behavior, what were your 7 responsibilities with regards to that? 8 A What I recall is a search of the database 9 for adverse events that would fall into 10 that category. 11 Q The violent aggression cluster events? 12 A Yes. 13 Q When you say search of the database, what 14 database? 15 A The clinical trial database. 16 Q O.U.S. or U.S.? 17 A I remember U.S. specifically. 18 Q To your knowledge was there ever a data 19 collection project done outside the U.S. 20 similar to -- strike that. To your 21 knowledge did Lilly perform a data 22 collection of violent aggressive behavior 23 adverse events outside the U.S. such as 24 they did with the suicide data collection PAGE 46 1 project? 2 A Not that I recall. 3 Q Any other projects with regards to violent 4 aggressive behavior and the use of 5 Fluoxetine? 6 A No. 7 Q Let's talk about the international data 8 gathering project for a couple minutes. 9 Can you tell me when it was decided that 10 that project would be done? 11 A I don't remember. 12 Q Do you know if it was before or after 13 January of 1990? 14 A I don't remember. 15 Q Were you over in Europe working with that? 16 A No. 17 Q Who decided that the project should be 18 done? 19 A Senior management at Lilly. 20 Q Can you give me some names? 21 A Dan Masica, Leigh Thompson, Allan 22 Weinstein, Bob Zerbe. 23 Q Anybody else? 24 A That's all that I recall. PAGE 47 1 Q How about Dr. Heiligenstein, was he 2 involved in that? 3 A He was involved, but not one of those in 4 position to make that decision. 5 Q How about Dr. Wheadon? 6 A Same. 7 Q Do you know why they decided to do it? 8 A Decided to do what? I'm sorry. 9 Q To perform the international database 10 gathering. 11 A We knew that there was additional 12 information out there on patients being 13 treated in controlled clinical trials with 14 Fluoxetine and thought it might be helpful 15 in answering the question that was raised 16 by Dr. Teicher in his article. 17 Q So that would indicate that the project was 18 begun after Dr. Teicher's article came out; 19 correct? 20 A Yes. 21 Q Why was it that you had to go over to 22 Europe to gather the data instead of having 23 the data transferred to the U.S.? 24 MR. MYERS: When you say "you", PAGE 48 1 you don't mean her. 2 MS. ZETTLER: Generally, right. 3 THE WITNESS: Thank you. 4 A At that time when Lilly conducted clinical 5 trials, the trials conducted outside of 6 Indianapolis, the data were not collected 7 in the U.S. clinical trial database. 8 Q How come? 9 A We weren't organized in that way at that 10 time. We did clinical trials in the U.S. 11 to support registration with the FDA. 12 Those data were then shared with our 13 outside of the U.S. countries who would do 14 their own local studies to meet local 15 requirements in addition to what was 16 required by the FDA, and so the U.S. data 17 would be supplemented with the local 18 country's data for submission to those 19 regulatory agencies outside of the U.S. 20 Q So, for instance, if you were looking to 21 register the product in France, you would 22 give them the U.S. data as well as the 23 French data? 24 A Yes. PAGE 49 1 Q Would you give them data from any other 2 country besides the U.S. and France? 3 A If they requested it. 4 Q Does the FDA require final reports be 5 submitted on clinical trials that occur 6 outside the United States? 7 A To my knowledge they don't require the 8 submissions, but there is an annual 9 reporting procedure in which we include 10 manuscripts from foreign studies as well as 11 synopses of final reports conducted outside 12 of the U.S. so that the FDA is aware of 13 outside the U.S. activities on those drugs. 14 Q Who prepares the synopses and the final 15 reports for submission to the FDA, the 16 periodic submissions to the FDA, O.U.S.? 17 A The O.U.S. reports are prepared by Lilly 18 scientists within our affiliate countries 19 unless they're manuscripts and sometimes 20 those are prepared by the investigators 21 themselves who work on those clinical 22 trials. The annual report is prepared by 23 Lilly in Indianapolis, but the bits about 24 the O.U.S. data that are included in it are PAGE 50 1 prepared by those people O.U.S. who are 2 responsible for it. 3 Q Was this done in Indianapolis to assure the 4 accuracy of what's being reported by the 5 O.U.S. affiliates? 6 A You have to explain what you mean. 7 Q Well, I was just wondering if -- I mean, is 8 it a matter of the affiliates sending in 9 the synopses and the final reports for 10 inclusions to submissions to the FDA and 11 they're just taken at face value or are 12 they double-checked from a quality 13 assurance standpoint at Indianapolis? 14 A They would be reviewed by the clinical 15 scientists and the CRA working in that 16 particular area, whoever had responsibility 17 for that annual report. If it's a 18 manuscript that's been published, it 19 probably wouldn't be scrutinized other than 20 to look through any safety information that 21 is included in that manuscript to make sure 22 that if it was required to submit a 1639, 23 that in fact was done. 24 If it was a final report to submit PAGE 51 1 to a regulatory agency in Indianapolis, 2 that clinical scientist would have been 3 involved in a review of that while it was 4 still in its draft stages before it was 5 finalized and submitted to the O.U.S. 6 regulatory agency. 7 Q How is safety information transferred to 8 Lilly in Indianapolis from the O.U.S. 9 affiliates? 10 MR. MYERS: When? At what 11 point in time? 12 Q Let's start when you first became a CRA. 13 A The DEN system is really a global system 14 and we ensured that our affiliates 15 understood what the FDA requirements were 16 for the criteria for serious. In some of 17 our affiliates we had a computer database 18 in a way that they could access it and so 19 they would enter those 1639s themselves 20 directly into the DEN system. 21 In other affiliates where that 22 computer system had not been made available 23 to them the information would have been 24 Faxed or called in by telephone to a PAGE 52 1 physician responsible in Indianapolis who 2 would file the DEN report. 3 Q What about those non-serious adverse events 4 that occurred during the clinical trials 5 outside the United States? 6 A Those would not have been reported other 7 than in the annual report. 8 Q Did various countries have various 9 requirements for seriousness? 10 A Each country has their own regulatory law 11 who all have their own criteria for what 12 they want reported and reviewed. Our 13 affiliates understand what the FDA 14 requirements are, and so that's what we 15 work to in terms of reporting adverse 16 events into the U.S., but locally they 17 would follow their own rules and 18 regulations. 19 Q So you may have a situation where an 20 adverse event is reported, say, from France 21 to the FDA, but it may not be reported to 22 the French regulatory authority? 23 A That could happen. 24 Q Are you familiar with CIOMS, C-I-O-M-S? PAGE 53 1 A Yes. 2 Q What is that? 3 A I don't know what the acronym stands for, 4 but it's an international -- I believe it's 5 the EEC, European Economic Community, 6 requirements for reporting of adverse 7 events. 8 Q Are you familiar with their requirements? 9 A To my knowledge the difference between the 10 FDA criteria for serious and CIOMS criteria 11 for serious is that CIOMS assesses 12 causality, and the FDA wants all reports 13 that meet criteria for serious regardless 14 of causality assessment. 15 Q Under CIOMS, who assesses the determination 16 for causality? 17 A To my knowledge it's either the medical 18 director or the physician monitor within 19 that country that's reporting the event. 20 Q When you say the medical director or the 21 physician monitoring, you mean the 22 manufacturer's medical director or 23 physician monitor; correct? 24 A I mean Eli Lilly's, yes. PAGE 54 1 Q Are there regulations that need to be 2 applied in determining causality? 3 A I do not know. 4 Q Do you know if CIOM has a definition for 5 causally-related? 6 A Again, I don't know. 7 Q Back to the international data gathering 8 project, what was the first step in that 9 project? 10 A Identifying what it was that we were 11 looking for. And when I mean looking for, 12 we've done a huge number of studies with 13 Fluoxetine. They're collected in the 14 global project tracking system, GPT. And 15 the first step that I recall was 16 ascertaining exactly what we were going 17 after in terms of those studies, 18 identifying what studies, where they were, 19 the project planning aspects. 20 Q So when you say identifying what you were 21 going after, you mean deciding which 22 studies to review? 23 A Yes. 24 Q Okay. PAGE 55 1 A Thank you. 2 Q Sure. When you say all of the studies were 3 in the GPT, do you mean all the studies 4 that had been performed worldwide? 5 A Yes. 6 Q So there was some information -- strike 7 that. The GPT is maintained at Lilly, 8 correct, Indianapolis? 9 A What do you mean when you say maintained? 10 Q It exists at Lilly Indianapolis? 11 A Yes, but it sits on a computer in 12 Indianapolis, but all of our affiliate 13 offices have access to that system 14 remotely. 15 Q What type of information is kept in the 16 global project tracking system related to a 17 given project generally? 18 A General criteria about the study, a title, 19 the length, how many patients, what the 20 various drugs are that they're being 21 treated with; for instance, placebo, 22 Fluoxetine, a comparator of some sort, the 23 proposed start and end date to the study, 24 the names of the investigators. PAGE 56 1 Q Numbers of patients? 2 A Yes. 3 Q Is there a suicidality exclusion notation 4 in there? 5 A Not within GPT. 6 Q Were the results of the studies tracked by 7 GPT? 8 A At the time, no, they were not. There was 9 a requirement that a synopsis or abstract 10 at the end of the study would be a part of 11 GPT, but it was not -- based on the 12 computer, those synopses were kept in a 13 file within a group responsible for GPT in 14 Indianapolis. They were not computerized 15 at that time. 16 Q Safety information was kept in the GPT? 17 A Not to my knowledge. 18 Q Was there a particular type of study that 19 was looked at as a result of -- strike 20 that. Did you decide on using one 21 particular type of study as opposed to 22 other types of studies for the 23 international data gathering project? 24 A I don't recall all of the details, but I do PAGE 57 1 recall that we looked specifically at 2 trials in depression or related illnesses 3 like obsessive-compulsive disorder. We 4 also looked specifically at those studies 5 that were double-blind and had a comparator 6 arm rather than open-labeled studies. 7 Q Double-blind controlled studies? 8 A Yes. 9 Q When you say depression or related 10 illnesses such as OCD, what other illnesses 11 were considered depression-related? 12 A I remember one in particular in France 13 where they don't call depression 14 depression; it's described as melancholia, 15 so that would have been another area. 16 Others I don't recall. 17 Q Were there OCD trials included in the data 18 collection project? 19 A I believe so. 20 Q Why was it decided to focus on double-blind 21 controlled depression-related studies? 22 A So that scientifically you could make some 23 sense of the data that was gathered by 24 having a comparator arm. PAGE 58 1 Q At that time had clinical trials been 2 performed on other indications that were 3 also double-blind controlled studies? 4 A Yes. 5 Q Why were those studies not looked at? 6 MR. MYERS: Well, I'll object 7 to the form only to the extent she did say 8 OCD was included, so that's another 9 indication. 10 MS. ZETTLER: Other than what 11 we talked about. 12 MR. MYERS: Okay. 13 A The point that had been raised to my 14 knowledge at that point in time with regard 15 to questions about Fluoxetine involved 16 patients being treated for depression. The 17 other studies were in the area of obesity 18 and to my knowledge were still ongoing at 19 the time; they hadn't been completed. And 20 I believe that was another criteria in 21 looking at the studies. The trials had to 22 have been completed and the results 23 available. 24 Q How about bulimia trials? PAGE 59 1 A There was one in the UK, but it was ongoing 2 at the time. 3 Q How about other indications like smoking? 4 A Those trials were not done outside of the 5 U.S. We didn't pursue smoking outside of 6 the U.S. 7 Q Okay. Any other indications besides OCD, 8 obesity or bulimia that were performed 9 outside the United States? 10 A No. 11 Q How many trials had been performed outside 12 the United States on depression or 13 depression-related conditions? 14 A I do not recall the number. 15 Q Do you know if it was more than a hundred? 16 A I don't know. 17 Q Did you have that information at some point 18 in time as to that number of studies? 19 A I would have had it from the global project 20 tracking system. 21 Q From how many studies outside the U.S. were 22 data eventually collected? 23 A I don't recall the number. 24 Q Describe for me the process of how it was PAGE 60 1 decided that only double-blind comparator 2 depression-related studies would be looked 3 at. 4 A That was decided amongst the physician 5 group as they talked about the project with 6 input from our statisticians. 7 Q Is that the same group we talked about 8 earlier: Dr. Zerbe, Dr. Thompson, 9 Dr. Masica and Dr. Weinstein? 10 A No. At that point it would have been 11 Dr. Beasley, Dr. Wheadon, Dr. Heiligenstein 12 with input from those others that you named 13 but those three. Charles Beasley in 14 particular had the lead on that project. 15 Q At this point in time when you decided that 16 you were going to look at double-blind 17 controlled depression trials, had it 18 already been decided what you were going to 19 be looking for within those studies? 20 A No. 21 Q What was the next step after deciding what 22 types of studies to review? 23 A Finding out where they were. The data 24 resided in a number of places. I described PAGE 61 1 to you earlier how clinical research was 2 conducted in Europe with the affiliate 3 offices sending case report forms in to Erl 4 Wood, so a number of those case report 5 forms were in fact at our Erl Wood 6 facility, but there were also additional 7 studies that were run specifically in one 8 country, and so they would have been kept 9 locally, and that was the next step of the 10 project, getting in touch with the medical 11 directors in each of those countries, 12 asking where the case report forms for 13 particular studies were located. 14 Q To your knowledge did anybody request that 15 Lilly do analysis of the O.U.S. clinical 16 trials? 17 A No. 18 Q How did you go about locating where the 19 clinical trials were? 20 A By sending electronic mail messages or 21 calling directly the medical directors and 22 asking. 23 Q They sent you lists of the clinical trials 24 that they had performed or were in the PAGE 62 1 process of performing? 2 A No, we sent them lists of what we had 3 inquiring "Do you have the case report 4 forms from these? Can we have access to 5 them?" 6 Q Up to this point was Lilly working with 7 outside consultants in any manner with 8 regards to this project? 9 A We worked with a number of outside 10 consultants. I can't speak as to the 11 timing that they were involved. 12 Q When you say you worked with a number of 13 outside consultants, consultants in what 14 areas? 15 A Depression. 16 Q Any other areas? 17 A We also had a number of opinion leaders 18 involved in the review of our obesity data. 19 Q I'm sorry, you said opinion leaders? 20 A I'm sorry, yes. Yes, opinion leaders. 21 Q I'm sorry. I didn't understand what you 22 said. What do you mean when you say 23 opinion leaders? 24 A Experts in their field recognized by their PAGE 63 1 peers as being experts. 2 Q And you said that was related to the 3 obesity trials? 4 A Yes, but we also used those people in a 5 review of the OCD data, the bulimia data 6 and the depression data. 7 Q So these people were brought in after the 8 data was collected? 9 A We used consultants frequently in the 10 medical department on an ongoing basis. 11 Q When you say review of the data, what do 12 you mean, the obesity data, the OCD data, 13 the bulimia data? 14 A With the bulimia data in particular I 15 remember taking the clinical trial data and 16 working with a consultant to produce a 17 manuscript from that clinical trial. He 18 was one of these opinion leader designated 19 physicians and he came in and spent some 20 time with us reviewing the results of the 21 clinical trial that were submitted to the 22 FDA and then prepared a manuscript article 23 from that data that we made available to 24 him. PAGE 64 1 Q Was he an author on the manuscript? 2 A Yes. 3 Q What's the difference between an outside 4 consultant and an opinion leader? 5 A There's really not a difference. I would 6 use those interchangeably. 7 Q Is this in your mind though a separate 8 group of people? Were the opinion leaders 9 brought in specifically to work on, say, 10 like obesity, OCD or bulimia where the 11 others were brought in generally? 12 A No. We had a number of individuals that we 13 worked with routinely and just depending on 14 the nature of the project that we were 15 working on, you would call one, two, 16 three -- a group -- for whatever you really 17 needed their expertise for. 18 Q Did you use consultants on the issue of 19 suicidality? 20 A Yes. 21 Q How many consultants did you use on that? 22 A I don't recall. 23 Q What were those consultants used for? 24 A I specifically remember their involvement PAGE 65 1 in a review of the analyses once the data 2 had been collected in preparation for that 3 1990 FDA meeting. 4 Q And when you say a review of the data, you 5 mean the United States data; correct? 6 A At that time we also had some of the O.U.S. 7 data. 8 Q When was the O.U.S. data project completed? 9 A The data collection had been completed 10 before I started my role at Erl Wood. The 11 analysis was not completed until after I 12 was already in the UK. 13 Q Was the O.U.S. data collection project 14 completed before the September '90 meeting 15 with the FDA? 16 A No. 17 Q Were one of these consultants on 18 suicidality Dr. Jan Fawcett? 19 A I don't recall their names. 20 Q Were they all men? 21 A That I do remember, yes. 22 Q Are you familiar with Dr. Ivan Miller? 23 A No. 24 Q Did you use any consultants on violent PAGE 66 1 aggressive behavior? 2 A I don't remember. 3 (A discussion was held off the record.) 4 Q Were consultants used to decide which types 5 of trials to look at in the O.U.S. data 6 gathering project? 7 A No. 8 Q Were they used to decide the definitions of 9 suicidal ideation, suicide attempt and 10 suicide? 11 A Not that I recall. 12 Q To your knowledge were they used at all 13 prior to the data collection being 14 completed? 15 A No. 16 Q So their main function was to review and 17 analyze data that was provided to them? 18 A Not analyze it. They reviewed it. After 19 the analysis had been done, they reviewed 20 what it was that were the results, if you 21 will, and commented on those results. 22 Q You mean after the statistical analyses and 23 everything were run on the data? 24 A Uh-huh. PAGE 67 1 Q You have to say yes or no. 2 A Yes. Sorry. 3 Q That's okay. Were these men outside the 4 U.S. or from the U.S.? 5 A U.S. 6 Q Did you work with any consultants outside 7 the United States on the issue of 8 suicidality? 9 A No, I did not. 10 Q How about anybody at Lilly, did Lilly use 11 outside consultants, outside of the United 12 States consultants? 13 A I recall our physicians making trips to 14 Europe to talk to consultants in Europe, 15 but I don't remember any O.U.S. consultants 16 being brought to Indianapolis for 17 discussion. 18 Q When in relation to the O.U.S. data 19 gathering project did physicians from 20 Indianapolis talk with consultants outside 21 the U.S.? 22 A It would have been during and after that 23 data gathering. 24 Q Was that consultation done in relation to PAGE 68 1 the O.U.S. data gathering project? 2 A No. 3 Q Was that done in relation to the September 4 of 1990 meeting with the FDA? 5 A No. 6 Q Why was it done? 7 A I recall it being done in response to the 8 appearance of the Teicher article. 9 Q Were they asked to write reports? 10 A I don't know. 11 Q Were the results of the consultations used 12 in any way either in a manuscript or in a 13 submission to the FDA? 14 A Not to my knowledge. 15 Q Why not? 16 A I don't know. 17 Q Was that a project separate and apart from 18 the O.U.S. data gathering project -- or 19 strike that -- yes, the O.U.S. data 20 gathering project and the United States 21 data review projects? 22 A Yes. 23 Q Who was involved in that project? 24 A It would have been discussions between PAGE 69 1 Lilly research physicians and those outside 2 consultants directly. 3 Q Were these outside consultants people who 4 had worked on clinical trials for Lilly on 5 Fluoxetine? 6 A I don't know. 7 Q Do you remember how many consultants there 8 were? 9 A No, I don't. 10 (A discussion was held off the record.) 11 Q Let's see, we've got the deciding what 12 trials to use or to look at in the O.U.S. 13 data gathering project and finding out 14 where they were. 15 A (Affirmative nod). 16 Q And what happened after that? 17 A Okay. We requested that they send to us 18 case report forms like one or two as a 19 sample from those studies so we could see 20 what the data looked like that they had 21 gathered, what their case report forms 22 looked like. For instance, we knew that 23 some in the local countries, the ones not 24 at Erl Wood, may have been in their own PAGE 70 1 local language. 2 Knowing that they weren't on a 3 central database because they resided 4 either locally or within the Erl Wood 5 facility and all these case report forms 6 were different in format -- not necessarily 7 in content, but different in format -- we 8 then designed a data collection form for 9 those data elements that we wanted to 10 capture after a review of those sample 11 cases. 12 Q So from reviewing the various samples from 13 the various affiliates, you designed a data 14 collection form that would be consistent 15 across the board? 16 A Yes. 17 Q And this form was called a work sheet; 18 correct? 19 A Yes. 20 Q What types of information was collected on 21 the work sheet? 22 A Patient identification, information about 23 adverse events and depression rating 24 scales. Here we tend to use the Hamilton PAGE 71 1 rating depression scale and in Europe they 2 use what's called the MADRS. I don't 3 remember what it stands -- oh, wait -- 4 Montgomery Asberg Depression Rating Scale, 5 M-A-D-R-S. 6 In some of the trials the HAM-D was 7 included; in others just that MADRS was 8 used, so we designed the forms to be able 9 to collect one or both of those, also a 10 review of any comments that the 11 investigator may have written on those 12 forms particularly with regard to adverse 13 events. 14 Q Any efficacy information that was 15 collected? 16 A The efficacy information would have been in 17 those rating scales. 18 Q Okay. Any other scales besides the 19 depression-related scales that were 20 collected? 21 A Not that I recall. 22 Q Would it be fair to say that the focus of 23 the data collection was more on safety than 24 on efficacy? PAGE 72 1 A Yes. 2 MS. ZETTLER: Can we take 3 another quick break? I've got to call the 4 office. 5 MR. MYERS: Sure. 6 (A brief recess was taken and the 7 previous question and answer were read back 8 by the reporter.) 9 Q Who designed the work sheet? 10 A It was probably a team of people involving 11 the physicians and the CRAs. 12 Q Were you involved in that process? 13 A In a review, (affirmative nod). 14 Q How long was the work sheet? 15 A I don't recall the exact number of pages. 16 Q Was it longer than one page? 17 A Yes. 18 Q Was it as long as a CRF? 19 A No, it was shorter. 20 Q So the decision on what information to 21 gather was made by the physicians? 22 A Uh-huh. 23 MR. MYERS: Yes? 24 A Yes, with input from the statisticians. PAGE 73 1 Q After the work sheet was developed, what 2 was the next step? 3 A I'll call it logistical planning, 4 assembling a team of people to go to where 5 the data actually resided -- be that Erl 6 Wood or the local countries -- to work with 7 medical staff in those countries to 8 transpose the data from their case report 9 forms onto our work sheet. 10 Q When you say assemble a team, you mean a 11 team from Indianapolis? 12 A Yes. 13 Q Why was it necessary to send a team from 14 Indianapolis to the various sites outside 15 the U.S.? 16 A The group within Indianapolis were the ones 17 who had designed the forms who knew what 18 work had been done in the U.S. and 19 therefore in order to be most consistent 20 with that project, it was thought best to 21 send them to work with the local people to 22 make sure that the data were gathered 23 appropriately. 24 Q When you say who were familiar with what PAGE 74 1 work was done in the U.S., you mean on the 2 data analysis on suicidality done in the 3 United States? 4 A Yes, the things that were looked for within 5 the U.S. case report forms. 6 Q Were the work sheets structured to reflect 7 the same types of information that were 8 reviewed in the U.S. data review? 9 A Yes. 10 Q Were each of the sites that had information 11 on double-blind controlled depression-type 12 studies visited by somebody from 13 Indianapolis or were some of the studies 14 transferred to other sites for review? 15 A Some of the studies were transferred to 16 other sites for review. 17 Q I take it Erl Wood was kind of like the 18 main site that was used? 19 A Yes. 20 Q What other sites were used? 21 A Germany, Austria, our UK office in 22 Basingstoke. I don't recall any others. 23 Q Any in Italy? 24 A Yes, and Spain. PAGE 75 1 Q France? 2 A Yes. 3 Q Japan? 4 A No. 5 Q Was the team sent from Indianapolis given 6 any special training before they went over 7 there? 8 A Yes. 9 Q What did that training consist of? 10 A Review of the work sheet and understanding 11 of the data collection fields and also the 12 process by which we wanted that data to be 13 gathered. 14 Q Were you the supervisor over the group that 15 went to Europe? 16 A Yes. 17 Q So the training included review of the 18 work sheet, understanding of collection 19 fields and the process by which data was to 20 be collected; correct? 21 A Yes. 22 Q What was the process by which the data was 23 to be collected? 24 A The team going into each country had to be PAGE 76 1 assured that all of the patient data were 2 available. They then worked to transcribe 3 the local case report form data onto the 4 work sheet. A second person then did a 5 comparison to check that all the data had 6 been correctly transposed. 7 Q Quality control kind of? 8 A Yes. They were then boxed and shipped in 9 batches as they were completed to 10 Indianapolis. 11 Q When you say they were boxed and shipped, 12 you mean the work sheets, the completed 13 work sheets? 14 A Yes. 15 Q Were work sheets completed on every patient 16 in the double-blind controlled depression 17 trials? 18 A To my knowledge, yes, they were. 19 Q And they were all sent back to the United 20 States? 21 A Yes. 22 Q Why weren't the CRF's copied? 23 THE REPORTER: Were or weren't? 24 MS. ZETTLER: Weren't, were PAGE 77 1 not. 2 A I'm sorry. Can you repeat that? 3 Q Well, were the CRF's copied and sent back 4 to the United States with the work sheets? 5 A Some of them were. 6 Q Okay. Which ones? 7 A If there were any instances where 8 suicidality may have been described, either 9 within the rating scales there are specific 10 questions that deal with suicide or as an 11 adverse event or comments written by an 12 investigator, that case report form would 13 have been photocopied and sent to accompany 14 the work sheet. If there was no indication 15 of any of that, the case report form was 16 not sent but was kept locally. 17 Q When you say the case report form, do you 18 mean all case report forms for every visit 19 of that patient? 20 A Yes. 21 Q So it wasn't just limited to the case 22 report form, say, for Visit 4 where the -- 23 A No. 24 Q -- suicidality issue came up? PAGE 78 1 A No, it would have been the whole patient 2 record. 3 Q How long did the actual collection portion 4 of the data collection project take? 5 A I don't recall the exact dates. I believe 6 it took a couple months. 7 Q So these Lilly employees from Indianapolis 8 were over in Europe for a couple of months? 9 A Yes. 10 Q We've got deciding what trials should be 11 looked at, finding out where the trials 12 were, sending the -- gathering samples of 13 the clinical report forms from the various 14 studies, designing and -- strike that. I'm 15 just trying to make sure I haven't missed 16 anything here, okay? Deciding which 17 trials, finding out where the trials were, 18 gathering samples of the clinical report 19 forms from the various trials or the 20 various countries, and designing the 21 work sheet as well as putting together the 22 team and training them; correct? 23 A Yes. 24 Q And the next step was their actually going PAGE 79 1 over to Europe to gather the data? 2 A Yes. 3 Q Were there any problems that came up during 4 the collection process? 5 A Not to my knowledge. 6 Q Did the Indianapolis team work with 7 personnel at the various affiliates? 8 A Yes, they did. 9 Q Was there a goal? Strike that. Do you 10 know how many patients' case report forms 11 were to be reviewed? 12 A No, I don't. 13 Q Was there a goal for completion of the 14 project? 15 A What do you mean by "goal"? 16 Q Did you have a date where you were going to 17 try to get the data all collected and 18 returned to Indianapolis by? 19 A We estimated how long we thought the 20 project would take, and so there was a goal 21 date, but it was very flexible. And in 22 fact I'm sure that we went past it by a 23 week or two. 24 Q Do you remember when the team went over to PAGE 80 1 Europe? 2 A No, I don't. 3 Q Then the data was collected through the 4 process we just talked about; correct? 5 A Yes. 6 Q Were they to review clinical report forms 7 for every visit for every patient? 8 A Yes. 9 Q And were to fill out work sheets on each 10 visit? 11 A Yes. 12 Q Was there one work sheet that was used 13 consistently for all visits or was there 14 like a different work sheet that would be 15 used for gathering demographic data that's 16 collected on the first visit and then 17 another work sheet that's used on the 18 follow-up visit? 19 A I don't recall that level of detail. 20 Q What was done with the work sheets after 21 they were sent back to Indianapolis? 22 A We had a clerical person who essentially 23 logged them in making sure that we did 24 receive everything that had been sent, that PAGE 81 1 nothing had been lost. They were then 2 entered into a data entry system that our 3 systems folks put together for this 4 project. 5 Q When you say the work sheets were logged, 6 what do you mean? 7 A As the boxes were packed, we had a form 8 that we used to capture the contents of the 9 box. That form, a copy of that form, was 10 Faxed to Indianapolis so we knew what to 11 expect. When the boxes arrived, another 12 copy of that form was included in the box 13 with those case report forms and so we had 14 a staff person review the two lists but 15 also the contents of the box to make sure 16 that everything was there. 17 Q And who was that staff person? 18 A The main person involved, her name was Vivi 19 Farley. 20 Q What type of information was contained in 21 the log? 22 A The identification of the study, 23 investigator number and patient number and 24 visit number. PAGE 82 1 Q So it was the patient, investigator, 2 project number as well as the visit number? 3 A Yes. 4 Q After the work sheets were logged and you 5 said they were entered into the data entry 6 system created specifically for the 7 project; correct? 8 A Yes. 9 Q Was there a name for that database? 10 A I don't remember. 11 Q I take it there was a computer screen, a 12 file created that was similar to the 13 work sheet as far as the information that 14 it asked for? 15 A Yes. 16 Q Anything else included on that screen other 17 than the work sheet information? 18 A Not to my knowledge. 19 Q After the work sheets were logged and 20 entered into the data entry system, what 21 happened next? 22 A I can't really speak to that because that 23 project was ongoing when I took up my new 24 responsibilities in England. PAGE 83 1 Q Have you ever heard the term "hits"? 2 A Hits? 3 Q Yes. 4 A Baseball? 5 Q No, with regards to the data collection 6 project? 7 A No. 8 Q Do you know what happened to the 9 work sheets related to suicidality? 10 A They were reviewed by the physicians on an 11 ongoing basis as they came in to 12 Indianapolis. 13 Q Tell me how that process worked. 14 A I don't recall the specific details other 15 than after they were data entered, they 16 were put on the physician's desk or placed 17 in the hands of the physician -- Charles 18 Beasley, John Heiligenstein, David 19 Wheadon -- to review. 20 Q Did Dr. Beasley, Dr. Heiligenstein and 21 Dr. Wheadon all review the same work sheets 22 and CRFs? 23 A I don't remember what their process was. 24 Q What happened with the work sheets after PAGE 84 1 they were reviewed by the doctors? 2 A I don't know. 3 Q Have you ever heard of a man named Paul 4 Leber? 5 A Yes. 6 Q Can you tell me who Mr. Leber is, or 7 Dr. Leber, I'm sorry. 8 A I don't know what his exact title is, but 9 he's the head of the Neuropharmacology 10 Division at the FDA. 11 Q Have you ever met Dr. Leber? 12 A Yes, I have. 13 Q On what occasion or occasions? 14 A I've met him a number of times at outside 15 professional meetings, workshops. He was 16 also present at the FDA meeting in 17 September of 1990. 18 Q I take it you know Dr. Leigh Thompson? 19 A Yes. 20 Q How do you know Dr. Thompson? 21 A Dr. Thompson was the director responsible 22 for the medical division when I joined 23 medical as a CRA. He was also involved in 24 a management leadership role in the PAGE 85 1 analysis of the clinical trial database 2 surrounding suicide and the Teicher article 3 in the preparation for the FDA meeting. 4 MS. ZETTLER: I'm going to ask 5 her to read that back. 6 (The previous answer was read back by 7 the reporter.) 8 Q When you said the analysis of the clinical 9 trial database, you talked about the U.S. 10 database? 11 A Yes. 12 Q And the meeting you're referring to is the 13 September '90 meeting? 14 A Yes. 15 Q Do you know what Dr. Thompson's 16 relationship to Dr. Leber is if any? 17 A No. 18 Q Were you involved in putting together 19 materials for the FDA in preparation for 20 the September '90 meeting? 21 A Yes. 22 Q What was your involvement in that project? 23 A I remember a brief summary report on what 24 had -- what we had done and what we had PAGE 86 1 found in a review of the database. The 2 clinical trial database was prepared and 3 sent to the FDA before the meeting 4 occurred. My role was working with the 5 physicians, our medical writer, the 6 statisticians, the systems people to 7 prepare that draft and in a review of it. 8 Q Had the analysis of the United States 9 clinical trial databases related to 10 suicidality already been completed by that 11 time? 12 MR. MYERS: The time that she 13 did this project? 14 MS. ZETTLER: Right. 15 A I believe that a preliminary analysis had 16 been done. I think that the work continued 17 beyond that time. 18 Q To your knowledge did Drs. Heiligenstein, 19 Beasley and Wheadon review CRFs for 20 suicide-related or suicidality-related 21 adverse events from the clinical trials in 22 the United States similar to the review 23 that was done from the O.U.S. data 24 gathering project? PAGE 87 1 A Yes, they did. 2 Q With regards to the U.S. database review 3 were OCD trials taken into consideration 4 during that review as well? 5 A I believe that they were. 6 Q And that's because they are related to 7 depression? 8 A Yes. 9 Q Were you involved in the project to review 10 the U.S. clinical trial data? 11 A Yes. 12 Q What was your involvement in that? 13 A Working with our systems people again to 14 identify what studies in the U.S. database 15 should be reviewed. There was also a 16 project of clinical trials that had been 17 completed years earlier in which comments 18 that the investigator may have written on 19 the case report forms were not captured in 20 the computer database and so we had a hand 21 review of all those visits for all those 22 patients to make sure that there weren't 23 any references to serious adverse events, 24 suicide in particular, within those PAGE 88 1 comments. 2 Q Do you know if the decision to use the 3 double-blind controlled depression-related 4 studies was made initially in conjunction 5 with the U.S. data review? 6 A I don't recall. 7 Q Take me through the steps of the U.S. 8 clinical trial database review project. 9 Was it similar to what you did with the 10 O.U.S.? What was the first step? 11 A Which aspect of it? 12 Q Well, why don't you tell me what the 13 different aspects were. 14 A In my mind there were two projects: One 15 was the review of all the data that were 16 captured within the computer for the 17 clinical trial database. That involved 18 working to identify similar to the U.S. 19 process what studies were in the U.S. 20 database that met the criteria we were 21 looking for, the double-blind controlled 22 studies, then working with our systems 23 folks with the physicians to identify what 24 adverse events or related terms we should PAGE 89 1 be looking for, a review of the DEN 2 database for adverse events meeting 3 criteria for serious, a review of comments 4 that would have been included in those case 5 report forms by those investigators. 6 The second project was the one that 7 I mentioned earlier where we knew there 8 were a number of studies done much earlier 9 where the comments would not have been 10 captured on the computer, although the 11 adverse event fields and serious reports 12 into DEN would have happened, but on the 13 off chance that there was something in 14 those comments, we reclaimed all of those 15 case report forms from our warehouse, put 16 them in a conference room like this and 17 assembled a team of people who sat there 18 for approximately a week and reviewed all 19 those case report forms by hand looking for 20 notes that the investigator would have made 21 on a comments page or in the margins 22 related to adverse events. 23 Q And that was all done by hand? 24 A Yes. PAGE 90 1 Q The second project? 2 A Yes. 3 Q With regard to the second project, the 4 physical review of the case report forms, 5 was there a work sheet that had been 6 created similar to the O.U.S. work sheet 7 that was filled out? 8 A No. 9 Q What was done in the case of the O.U.S.? 10 MR. MYERS: O.U.S.? 11 Q Or U.S. physical review? 12 A Those case report forms, if there were any 13 specific notations regarding suicide, those 14 case report forms would have been taken 15 directly to the physicians. 16 Q What was the physicians' job in reviewing 17 the case report forms? What was the 18 purpose for them in reviewing them? 19 A Clinically review the information that was 20 contained within those related to suicide. 21 Q For what purpose? 22 A I can't speculate on that. 23 Q Were they to make a decision as to whether 24 or not a particular act was actually a PAGE 91 1 suicide attempt? 2 A Again, I can't answer it. 3 Q Would the same hold true for the review of 4 the work sheets? 5 A Yes. 6 Q In regards to the first part of that 7 project or the first project, the review of 8 the clinical trial database, I believe you 9 said the database was reviewed to first of 10 all see what studies were done; correct? 11 A The first part of that project would have 12 been again going into global project 13 tracking to identify all the studies that 14 had been done in the U.S., yes. 15 Q And then decide which of those studies were 16 going to be analyzed? 17 A Yes. 18 Q And then I believe you said that adverse 19 event terms were chosen to be used? 20 A Yes. 21 Q Okay. And the DEN database was searched 22 for serious adverse events from those 23 trials? 24 A Yes. PAGE 92 1 Q And if there were serious adverse events 2 that were found, say, in the DEN database 3 related to suicidality, what would happen 4 with those events; in other words, would 5 the physicians then review those events, 6 also? 7 A Yes. We would have pulled out the 8 documentation around those patients and the 9 physicians would have reviewed the whole 10 history of that patient as we knew it, all 11 the case report form visits. 12 Q Would the same hold true for any 13 suicide-related adverse events that were 14 found in the clinical trial database? 15 A Yes. 16 Q Was this a way that the suicidality adverse 17 events from the U.S. clinical trial 18 database were tracked while they were in 19 the process of being transferred to the 20 physicians and reviewed and things of that 21 nature? 22 A You'll have to help me with your question. 23 Q Sure. What I'm trying to find out is, is 24 it just a matter of, okay, this suicide PAGE 93 1 popped up on the clinical trial database, 2 so we're going to go pull the CRFs and give 3 them to the doctor and then whatever he 4 does with them, he does with them or is 5 there some process by which somebody keeps 6 track of what happens with those CRFs? 7 A In the hand manual review there was a 8 tracking process. We had a printout from 9 the computer of all the visits that had 10 occurred and all the patients that were 11 involved so we could make sure that as they 12 were reclaimed from the warehouse, for 13 instance, we didn't miss any and they were 14 checked off one by one as they were 15 reviewed. 16 For the clinical trial database, 17 again there would have been printouts of 18 all the patients involved in a study, and 19 those in particular where suicide or 20 related events would have been found, they 21 would have been marked on these lists so 22 that we could keep track of what specific 23 patients were involved. 24 Q But did somebody keep track of like, say, PAGE 94 1 Dr. Heiligenstein is looking at the CRFs 2 from Patient A? 3 A Not that I recall. 4 Q Help me out with the clinical trial 5 database itself. Is this one database 6 including information from all clinical 7 trials or are there databases created for 8 each clinical trial that's performed, 9 United States clinical trials? 10 A There's a data entry system built for each 11 clinical trial, but all that data resides 12 in one database. 13 Q I take it once it was decided which 14 clinical trials to focus on in the United 15 States clinical trial database review that 16 the information from those clinical trials 17 were pulled from the database? 18 A Yes. 19 Q Where were they transferred to? 20 A Paper. 21 Q So every single clinical report form for 22 every single patient in that study if it 23 was chosen was printed out? 24 A No. We would have searched in the capture PAGE 95 1 for a number of criteria: One was adverse 2 event terms related to suicide. The way 3 that those searches were run it would print 4 out patients in which those events occurred 5 and whatever the events were would also be 6 listed. 7 Q Now, would it be that you would get a 8 printout for suicides or suicidality for 9 every single clinical trial whether or not 10 it was one of the ones you were going to 11 focus on or was there a way that you 12 narrowed it down to just those clinical 13 trials that you were focusing on? 14 A A way to narrow it down. 15 Q How was that done? 16 A The systems analysts would have defined 17 what studies were searched within the code 18 or instructions that they wrote within 19 their programs. 20 Q To your knowledge has there ever been a 21 search of the entire clinical trials, 22 United States clinical trial database, 23 regardless of what the clinical trial was? 24 A Yes, that was done. PAGE 96 1 Q When was that done? 2 A I recall that it was done before this 3 exercise actually started, the one that 4 we've just been talking about. 5 Q Do you recall what the results of that 6 search were? 7 A No, I don't. 8 Q Was that memorialized on paper? 9 A Yes. 10 (Deposition Exhibit 1 was marked for 11 identification.) 12 Q Go ahead and take a look at it. 13 A (Witness complies). 14 Q Do you recognize the Exhibit No. 1? 15 A No, I don't. 16 Q Is that your handwriting at the top of the 17 page? 18 A No, it's not. 19 Q The memorialization of the search of the 20 entire clinical trial database, does it 21 look something similar to this? 22 A Not that I recall. 23 Q Describe for me what the entire clinical 24 trial database search looked like in paper PAGE 97 1 form. 2 A What I recall is one or two acetates where 3 it was summarized for the presentation in 4 September of 1990 for the FDA where we 5 looked at events, incidence of events that 6 had occurred in depression studies and the 7 incidence of events that had occurred in 8 non-depression studies those being obesity, 9 bulimia, smoking cessation, et cetera. 10 Q So it was just totals that were listed? 11 A That's what I remember seeing. 12 Q Do you ever recall seeing anything like 13 this related to the search of the entire 14 database? 15 A No. 16 Q Do you recall seeing anything similar to 17 Exhibit No. 1 related to the O.U.S. data 18 collection project? 19 A No. 20 Q Do you have any idea why this would have 21 been produced as being part of your file, 22 do you know? 23 A No, I don't. I don't recall seeing this 24 before today. PAGE 98 1 Q Have you seen similar listings of 2 suicide-related adverse events? 3 A Not in a format like this. 4 Q In any other format? 5 A From the clinical trial database. This 6 looks like a report from the DEN system; 7 that's how it's titled. And I have seen 8 reports that instead of listing these 9 fields would have listed the patient, 10 investigator, visit information that we 11 talked about earlier and what adverse event 12 terms would have been included in those 13 visits. 14 Q So it would have been a matter of like, 15 say, Patient So-and-So, Visit One, whatever 16 adverse event was suffered on that date? 17 A Yes, those are the kinds of reports that 18 I'm used to seeing. 19 Q Were you aware that as of July 7th, 1990 20 there were over 1,000 suicide-related 21 adverse events reported in the DEN system? 22 A No, I wasn't. 23 MR. MYERS: Well, I object to 24 the form only to the extent that I think PAGE 99 1 it's actually September. 2 MS. ZETTLER: I'm sorry, 3 September. 4 MR. MYERS: Unless maybe the 5 month is in the middle; I don't know. Do 6 you see what I mean? 7 MS. ZETTLER: Yes. 8 Q Were you aware at that point that there had 9 been that many adverse events related to 10 suicide that had been reported to the DEN? 11 A No. 12 Q Were you ever aware that there had been 13 that many suicide-related adverse events 14 reported in clinical trials in the DEN at 15 any time? 16 A No, I was not. 17 (Deposition Exhibit 2 was marked for 18 identification.) 19 Q Do you recognize this exhibit? 20 A Yes, I have seen it before. 21 Q Can you tell me what it is. 22 A A summarization of a phone call that Leigh 23 Thompson had with Paul Leber from the FDA. 24 Q Does this refresh your recollection as to PAGE 100 1 when Lilly decided to do the various data 2 collection and analyses projects? 3 A No, it doesn't. 4 Q Is it your recollection that the U.S. data 5 gathering or data analysis project was done 6 prior to July 18th, 1990, which is the date 7 of this memo? 8 A I believe that it was ongoing at the time. 9 Q Did you ever discuss this memo with 10 Dr. Thompson? 11 A Not personally. 12 Q Do you agree with everything that's 13 contained in this memo? 14 MR. MYERS: Well, I object to 15 the form. There is a lot contained in the 16 memo. It was overly broad. 17 Q You're familiar with the memo, are you not? 18 A I'm familiar with the memo. 19 Q Are you familiar with the subject matter of 20 the memo? 21 A The subject matter being Prozac. I can't 22 speculate on what actually occurred in this 23 phone call between Dr. Thompson and 24 Dr. Leber. PAGE 101 1 Q Do you have any reason to believe that 2 Dr. Thompson reported something in the memo 3 that did not take place in a conversation? 4 A No. 5 Q Did you ever discuss with Dr. Leber what he 6 meant on the second page, second to the 7 last paragraph, when he says "the best that 8 can be done is to put a (quote) cap 9 (unquote) on the number of events"? 10 MR. MYERS: Which doctor? Did 11 she discuss it with who? You said Leber. 12 MS. ZETTLER: I'm sorry, with 13 Dr. Thompson. 14 A No, I did not. 15 Q Is it your understanding that it was Eli 16 Lilly's intention to cap the number of 17 events related to suicidality? 18 A No. 19 Q Was it your understanding that it was the 20 FDA's intention to put a cap on the number 21 of events that were reported related to 22 suicidality? 23 A No. 24 Q Were you aware of what's reported in the PAGE 102 1 fourth paragraph from the bottom by 2 Dr. Thompson that Dr. Leber's computer had 3 been broken into? 4 A I knew that from this memo, but was not 5 aware of any circumstances or other 6 information. 7 Q Do you know what Dr. Leber -- or I'm 8 sorry -- Dr. Thompson is talking about when 9 he states that Dr. Leber asked that Lilly 10 Fax nothing to him? 11 A Other than we often sent things to the FDA 12 to specific individuals if they wanted it 13 urgently by Fax and his comment that he 14 would appreciate it if we did not Fax it 15 unless he knew it was coming ahead of time, 16 which I can read here (indicating). 17 Q Were you told by anybody at Lilly at any 18 time not to Fax anything to Dr. Leber at 19 the FDA? 20 A No, I was not. 21 Q To your knowledge was that a policy at one 22 point, at any period of time at Lilly, not 23 to Fax information to Dr. Leber or anybody 24 at the FDA? PAGE 103 1 A No. 2 Q At the top of the second page Dr. Thompson 3 stated "I then informed him of the suicide 4 expert meeting next Tuesday". Were you 5 involved in that meeting? 6 MR. MYERS: Right there 7 (indicating). 8 A I don't recall. 9 Q Have you ever discussed this memo with 10 anybody at Lilly? 11 A Not that I recall. 12 Q To your knowledge was the O.U.S. data 13 gathering project review limited to studies 14 using only a 20 milligram dosage of 15 Fluoxetine? 16 A That I don't recall. 17 (Deposition Exhibit 3 was marked for 18 identification.) 19 A Okay. 20 Q Earlier you testified that there was a list 21 of clinical trials that were sent to the 22 various affiliates. Is this the list you 23 were talking about? 24 A This is not it. PAGE 104 1 Q What is this list? 2 A A standard update list that we had been 3 keeping for a number of years with some 4 general details about studies conducted in 5 various countries related to depression, it 6 looks like. 7 Q Was the list that was provided to the 8 affiliates longer than this, the list we 9 talked about earlier? 10 A I don't recall it being in this format. It 11 was more like a line listing that would 12 have been like a spreadsheet kind of 13 printout rather than in this format. 14 Q As far as the number of trials that were 15 discussed in the list that was sent out to 16 the affiliates in preparation for the 17 O.U.S. data gathering project, was the 18 number of studies in that list larger than 19 the number of studies in this exhibit? 20 A I don't recall. 21 Q The first couple of pages of the exhibit 22 are addressees; correct? 23 A Yes. 24 Q Who are these people? PAGE 105 1 MR. MYERS: Which ones? 2 Q The primary addressees. Now, just 3 generally; I don't need every single 4 person. 5 A Just generally in mind looking through the 6 list of people it's a mixture of some 7 medical directors, some physicians, some 8 CRAs, some managers, some marketing people 9 in those affiliate offices. 10 Q So these are all Lilly employees at the 11 affiliates? 12 A Yes. 13 Q On the second page it says South Africa, 14 Geneva, Homburg, Leo. What is Leo? 15 A Our office in London. It stands for Lilly 16 European Office. 17 Q So you have three offices in the UK? 18 A Yes, we do. There is also an additional 19 manufacturing site, so there are four Lilly 20 sites in the UK. 21 Q Have you ever heard of a Professor Moller, 22 M-o-l-l-e-r? 23 A No. 24 Q How about a Professor Ashcroft? PAGE 106 1 A No. 2 Q Dr. Katona, K-a-t-o-n-a? 3 A I've heard his name. 4 Q Do you know who Dr. Katona is? 5 A No. 6 (Deposition Exhibit 4 was marked for 7 identification.) 8 A Okay. 9 Q Are you familiar with this exhibit? 10 A Yes. 11 Q Can you tell me what it is. 12 A The first is a trip report basically from 13 Dr. Wheadon from the time that he was in 14 Europe, and the last page is a status 15 report from the project leader on the 16 O.U.S. data collection, Lisa DeVault. 17 Q Who is Lisa DeVault? 18 A She is -- was at the time a systems person 19 supporting the Fluoxetine efforts and she 20 had the role as project leader on the 21 ground in Europe for that data gathering 22 exercise. 23 Q So she was over in Europe? 24 A Yes, she was. PAGE 107 1 Q Did Dr. Wheadon's trip to Europe relate in 2 any way to the data gathering project 3 either directly or indirectly? 4 A It was done at the same time, but they were 5 two separate projects. 6 Q Does this refresh your recollection as to 7 who Professor Moller or Professor Ashcroft 8 and Dr. Katona are? 9 A No, other than they are obviously European 10 professors, but I don't recall their names. 11 Q Earlier you said that you were aware of 12 some consultants that were used from -- or 13 at least talked with by Lilly physicians 14 outside the U.S.; correct? 15 A (Affirmative nod). 16 Q Would this refresh your recollection of 17 that project? 18 A Yes. 19 Q On the last page where it says update 20 report when she says in the middle, there 21 she gives numbers for the different 22 affiliates -- 23 A Yes. 24 Q -- are these individual patient numbers or PAGE 108 1 are these visits? 2 A I don't know. I'm not sure. 3 Q Do you recall how many patient -- not 4 patient visits -- how many patients' CRFs 5 were reviewed on the project? 6 A I don't. 7 (Deposition Exhibit 5 was marked for 8 identification.) 9 A Okay. 10 Q Are you familiar with this exhibit? 11 A Yes. 12 Q Is this the line listing of clinical trials 13 that you were telling me about earlier? 14 A Yes. 15 Q So this is the listing that was sent to the 16 affiliates for their review; correct? 17 A Yes. 18 Q Is this the listing that was sent to them 19 after it was determined that these were all 20 double-blind comparator studies or was this 21 the listing of all clinical trials that had 22 been performed outside the U.S. at that 23 time? 24 A I believe this was the list after it had PAGE 109 1 been determined that they were double-blind 2 studies. 3 Q And the affiliate's job was to look over 4 the listing and make sure that it was 5 complete and correct; right? 6 A Yes. 7 Q Do you know if there were any major changes 8 to this listing? 9 A I don't recall. 10 Q Who is Catherine Mesner? 11 A At the time she was a CRA in the group when 12 I was a department head. 13 Q You were her boss? 14 A Yes. 15 Q What role did Catherine play in the O.U.S. 16 data collection project? 17 A She worked with a number of people to 18 actually design the data collection form 19 and take care of getting them duplicated 20 and shipped to the appropriate places where 21 the data would be transcribed. She also 22 worked with me on identifying where in fact 23 the visits were and organizing who amongst 24 the team would go to what countries, how PAGE 110 1 long they would need to be there, 2 et cetera. And Catherine was part of the 3 team that went to Europe and she in fact 4 did quite a bit of the work herself. 5 (Deposition Exhibit 6 was marked for 6 identification.) 7 A Okay. 8 Q Are you familiar with this exhibit? 9 A No, I don't remember it exactly. 10 Q If you look on the first page under point 11 number 5, it says "During transcription 12 obvious (quote) hits (unquote) can be put 13 aside for further review by a group yet to 14 be determined." Does that refresh your 15 recollection as to what hits are? 16 A Yes. 17 Q And what are hits? 18 A Patients or case report forms that would 19 have had information regarding suicide. 20 What we were looking for would have been 21 positive and therefore pulled out from the 22 rest of the data. 23 Q Does this refresh your recollection as to 24 how many trials were to be looked at in the PAGE 111 1 O.U.S. data gathering project? 2 A Yes, it does. It's captured here. 3 Q How many? 4 A According to this, it says 54. 5 Q Who is Margaret Kunkel? 6 A At the time she was a Medical Quality 7 Assurance representative at Lilly with 8 responsibility for Fluoxetine. 9 Q And what was MQA's role in this project if 10 any? 11 A They are an independent auditing group that 12 look at the work medical does and advises 13 on whether we're in compliance with the 14 Code of Federal Regulations among other 15 things. Peggy was consulted just in terms 16 of looking at our processes and commenting 17 on the quality of those to make sure that 18 we didn't really miss anything that was 19 there. 20 Q Did she in fact go to Europe? 21 A No, she did not. 22 Q Did anybody from MQA go to Europe? 23 A I believe that Dave Stalder went to Europe. 24 He was an associate of Peggy's. PAGE 112 1 Q Would you agree with Catherine's statement 2 in point number 2 that the work sheets 3 would be used solely for the purpose of 4 building a database for a suicide analysis? 5 A Yes. 6 Q The second page of the exhibit at the top 7 it says "Background for International 8 materials". Does this also refer to the 9 O.U.S. data collection project? 10 A Yes. 11 Q It states in here toward the middle of the 12 page under evaluation status, it says 31 of 13 68 protocols and CRFs received and 14 evaluated. That 68 number differs from the 15 number that's reflected on the first page. 16 Is this talking about clinical trials that 17 were reviewed, also? 18 A The 68 protocols refer to clinical trials. 19 Q Okay. So it could have been as many as 68 20 clinical trials that were reviewed in the 21 O.U.S. data gathering project? 22 A Yes, according to this memo. 23 Q Do you know what the requirements for 24 potential merging is? PAGE 113 1 A No. 2 Q What does this mean when it says potential 3 merging, if you know? 4 A As related to meeting the criteria for 5 being randomized, double-blind was those 6 clinical trials at a minimum had to have 7 those two characteristics in order to be 8 pulled together in a database to be 9 reviewed. 10 Q The next page at the top it says "Summary 11 of Montgomery protocol". 12 A Yes. 13 Q Are you familiar with that protocol? 14 A Not in detail. 15 Q Can you tell me what you know about that 16 protocol. 17 A It's a study that's been conducted in the 18 UK. BP is our code for the United Kingdom. 19 Montgomery is one of the investigators, the 20 lead investigator on that study. 21 Q Do you know if that study was completed? 22 A Yes, it was. 23 Q When was it completed? 24 A I don't recall the exact date but since the PAGE 114 1 time that I've been at Erl Wood. 2 Q To your knowledge has there been a final 3 report written on that study? 4 A Not to my knowledge. 5 Q Do you know what the results of that study 6 were? 7 A No, I don't. 8 Q Was a manuscript prepared regarding that 9 study? 10 A I don't know. 11 Q Do you know why the study was done? 12 A No. 13 Q Was it begun prior to January of 1990 when 14 Dr. Teicher's article came out? 15 A I don't know. It was ongoing by the time I 16 got to my job in the UK. 17 Q Have you ever seen a protocol for this 18 study? 19 A No, I haven't. 20 Q Have you done any work on this study? 21 A No, I haven't. 22 Q How is it that you knew that it was being 23 conducted? 24 A Within my group at Erl Wood, the case PAGE 115 1 report forms were entered into the database 2 at Erl Wood and there were CRAs in my group 3 who were working on it at the time that I 4 arrived in my position. 5 Q To your knowledge has anybody on this study 6 committed suicide? 7 A Not to my knowledge. 8 Q Anybody attempted suicide? 9 A Not to my knowledge. 10 Q How about the last page, it says 11 "Prospective studies O.U.S. background, 12 South Africa". 13 A Uh-huh. 14 Q Are you familiar with this study? 15 A This page I'm not familiar with. 16 (Deposition Exhibit 7 was marked for 17 identification.) 18 A Okay. 19 Q Does this refresh your recollection as to 20 when the team went over to Europe? 21 A Yes. It says in here in October. 22 Q Mid October 1990; correct? 23 A Yes. 24 Q And I think you testified earlier that it PAGE 116 1 was your recollection that they were over 2 there for about a month? 3 A I think longer than a month. 4 Q Do you remember how long total? 5 A No, I don't. 6 Q Was it more than two months? 7 A The bulk of the work I believe was done 8 within a two-month time frame primarily at 9 Erl Wood, but there were some other 10 countries, Spain and Italy, that I believe 11 stretched out beyond two months. 12 MS. ZETTLER: Can we break for 13 lunch? 14 MR. MYERS: That's fine. 15 16 (A lunch recess was taken.) PAGE 117 1 A F T E R N O O N S E S S I O N 2 DIRECT EXAMINATION (CONTINUING) 3 QUESTIONS BY NANCY ZETTLER: 4 (Deposition Exhibit 8 was marked for 5 identification and the requested testimony 6 was read back by the reporter.) 7 Q Do you recognize Exhibit 8? 8 A Yes. 9 Q Can you tell me what it is. 10 A It looks like the first page of the 11 document that was put together to describe 12 the process by which the data would be 13 gathered from Europe. 14 Q Did you have a role in drafting this 15 document? 16 A Yes. 17 Q Could you tell me what you did with regard 18 to this document. 19 A Actually I think I put it together. 20 Q How many pages long is the document? 21 A I don't recall. 22 Q More than one page though; correct? 23 A Yes. 24 Q What other types of information are PAGE 118 1 included in the document besides what is 2 shown in Exhibit 8? 3 A I don't recall. 4 Q Was this document given to the team that 5 went over to Europe to actually review the 6 data, review and collect the data? 7 A I don't recall if this exact document was 8 handed to them. 9 Q What does it mean at the bottom under 4a 10 where it says "The responsibility for 11 verifying that all serious ADEs have been 12 reported appropriately to regulatory 13 agencies will reside with the affiliate 14 medical staff"? 15 A The reporting of serious adverse events 16 into DEN from studies conducted outside of 17 the United States, that was the 18 responsibility of the affiliate so if there 19 were any questions regarding what 20 information had been reported, if it had 21 been reported, those kinds of questions, 22 those medical folks who worked in those 23 affiliates would look for follow-up 24 information, look in their DEN system, PAGE 119 1 et cetera. 2 Q Do you recall that there were serious 3 adverse events that had not been previously 4 reported to DEN that were found during the 5 data collection? 6 A No, I don't. 7 (Deposition Exhibit 9 was marked for 8 identification.) 9 A Okay. 10 Q Do you recognize this document? 11 A Yes, I do. 12 Q Is that your handwriting on the right-hand 13 side of the page? 14 A No, it's not. 15 Q Do you know whose handwriting that is? 16 A No, I don't. 17 Q What is this document? 18 A A report from Lisa DeVault from the time 19 that she was working in the UK. It seems 20 from this document that she was in the 21 Basingstoke office, not the Erl Wood 22 office. Just talking about how the project 23 was going. 24 Q Is it your understanding that clinical PAGE 120 1 report forms from affiliates such as South 2 Africa, Denmark and Finland were 3 transferred to the Basingstoke or the Erl 4 Wood affiliates for review? 5 A Yes, they were. 6 Q Were there clinical report forms that were 7 reviewed from countries outside of Europe 8 such as Asia, Japan, places like that? 9 A We hadn't done any studies with Fluoxetine 10 in Japan. 11 Q How about Taiwan? 12 A No. 13 Q Anywhere else besides South Africa outside 14 of Europe? 15 A Not to my knowledge. 16 (Deposition Exhibit 10 was marked for 17 identification.) 18 Q What's a patient transcription? 19 A Where are you looking? 20 Q Second full paragraph towards the bottom. 21 It says "Bottom line -- we are currently 22 approaching our predicted 30 minute per 23 patient transcription." 24 A We had some estimate based on some practice PAGE 121 1 ones that we did in Indianapolis with the 2 case report forms that they sent to us in 3 timing how long that took to glean the 4 information from their original case report 5 forms and transcribe it onto a work sheet 6 and we used that practice to estimate how 7 much time the total project would take. 8 Q When you say patient transcription from the 9 CRFs, is that the total CRFs for that 10 person or is that per visit? 11 A I believe that was for that patient. 12 Q Who is Dr. Keohane? 13 A At the time he was the medical director 14 responsible for the group at Basingstoke. 15 Q Does he still work for Lilly? 16 A Yes, he does. 17 Q Where is he now? 18 A In Indianapolis. 19 Q Do you see the paragraph where it talks 20 about Dr. Keohane towards the bottom of the 21 page? 22 A Yes. 23 Q Before I forget, you wrote this exhibit, 24 right, Exhibit 10? PAGE 122 1 A Yes. 2 Q And it's an E-mail dated October 25th, 3 1990? 4 A Uh-huh. 5 Q You have to say yes. 6 A Yes. 7 Q A couple paragraphs above that it says "For 8 those of of you curious about the results", 9 do you see that? 10 A Yes. 11 Q When you say you found two case report 12 forms out of 120 patients, do you mean two 13 case report forms out of 120 patients 14 related to suicide? 15 A Yes. 16 Q You may have answered this earlier and if 17 you did, I apologize, but was there a 18 database that was set up specifically for 19 the data gathered in the O.U.S. gathering 20 project? 21 A Yes. 22 Q Did that database have a name? 23 A I don't recall. 24 Q You don't recall whether or not it had a PAGE 123 1 name or it had a name and you don't recall 2 what the name was? 3 A I don't recall whether it had a name. 4 (Deposition Exhibit 11 was marked for 5 identification.) 6 A Okay. 7 Q Do you recognize Exhibit 11? 8 A Yes. 9 Q Can you tell me what it is? 10 A There are several parts to it. The first 11 pages that you have here are a listing of 12 all the studies involving Fluoxetine and 13 the names of the investigators that 14 participated in those studies for Lilly. 15 Q When you say -- let me interrupt you. When 16 you say the first parts of it, which pages? 17 You can tell me like the first four numbers 18 or whatever. 19 A Pages numbered 5, 6, 7, 8, 9, 10, 11. 20 Q In the upper right-hand corner? 21 A Yes, and 12. 22 Q I'm sorry. Go ahead. 23 A Pages 13 through 16 are another kind of 24 report and I'm not familiar with what it's PAGE 124 1 talking about where it says frequency and 2 percentage. Again, it's a list of project 3 protocols involving Fluoxetine, but I don't 4 know what those two columns refer to. And 5 the last table was from one of the 6 submissions that we made to the FDA and 7 it's a synopsis of all the studies that 8 were done at that time involving Fluoxetine 9 and some basic criteria about those studies 10 in terms of the number of patients entered, 11 completed, where those reports could be 12 found within that submission, et cetera. 13 Q Let's go back to the second section of the 14 exhibit starting with Page 13. 15 A Okay. 16 Q It says project, frequency and percentage; 17 correct? 18 A Yes. 19 Q You don't know what frequency they're 20 referring to there, do you? 21 A No, I don't. 22 Q Could that be frequency of adverse events? 23 A I honestly don't know. 24 Q Okay. Go back to the first page of the PAGE 125 1 exhibit. 2 A (Witness complies). 3 Q Up in the title of the page it says 4 "Listing Of All Projects And Investigators 5 On The Entrex, E-n-t-r-e-x, System." 6 A Yes. 7 Q What is the Entrex System? 8 A A data entry system that was in use at the 9 time that these studies were done. 10 Q What type of data would be entered in that 11 system? 12 A To my knowledge the clinical trial data 13 from the case report forms. 14 Q Would this be what has been commonly 15 referred to as the clinical trial database? 16 A Yes. 17 Q On the next page at the top it says 18 "General System." What's the General 19 System? 20 A Again, another clinical trial database that 21 would have been used for these studies. 22 Q What would be the difference between the 23 Entrex System and the General System? 24 A I don't know. PAGE 126 1 Q Have you ever heard the term Host System? 2 A Yes. 3 Q Is that General System the Host System? 4 A No. 5 Q What's the difference between the General 6 System and the Host System? 7 A In the way that the computer is organized 8 the General System is where the data was 9 initially entered. In the process of 10 reviewing and editing those data for 11 completeness you would get to a point where 12 you had all the data within Lilly for that 13 particular patient, then for that 14 particular study. When you had all the 15 data for a given study in your possession, 16 it would then be moved to the host computer 17 and that's where the statisticians and the 18 systems people would be able to access all 19 the data for a given trial and print out 20 the output reports that we talked about 21 earlier that were used to write final 22 reports. 23 Q On the next page it says Safety System. Do 24 you see that? PAGE 127 1 A That term I'm not familiar with. 2 Q This document is dated February 6, 1990; 3 correct? 4 A Yes. 5 Q Was that before or after you went to Erl 6 Wood? 7 A Before. 8 Q And then a few pages back, Page 10, it says 9 "Listing Of All Projects And Investigators 10 On Standards". Do you know what Standards 11 is? 12 A Yes. These were studies that were started 13 later in the clinical development of 14 Fluoxetine, and at this point in time we 15 went to a format of collecting data across 16 the different clinical trials that we ran 17 on all compounds, and the way that we 18 collected that we called standards so that 19 you could move from one drug to another and 20 collect similar pieces of data from the 21 same submission. 22 Q So, for instance, demographic data about 23 patients would be consistent across the 24 board? PAGE 128 1 A Yes. 2 Q Why would you want to collect data on 3 patients generally regardless of the 4 product? 5 A I don't understand your question. 6 Q Maybe I misunderstood you then earlier. 7 When you say that you wanted to track 8 information across the board, you meant 9 like within a certain product or across the 10 board on all products? 11 A We would use it within our group for 12 tracking across all studies on that 13 compound, but in terms of Lilly personnel 14 training and who worked on what compounds, 15 there were also advantages in doing 16 clinical trials in a standard fashion from 17 a training imitation standpoint. 18 Q So it was more for just standards and 19 practices with regard to clinical trials? 20 A Yes. 21 Q In at least the first portion of this 22 exhibit why were these lists compiled if 23 you know? 24 A I don't recall the specific reason that PAGE 129 1 this would have been printed out in 2 February of 1990. 3 Q Was this done in relation to the review of 4 the U.S. clinical trial database? 5 A I don't know. 6 Q Are you familiar with the term rechallenge 7 study? 8 A Yes. 9 Q Can you tell me what a rechallenge study 10 is? 11 A In the way that I understand it patients 12 who have had an adverse event in which the 13 investigator feels that it could cause -- 14 could possibly causally be related to the 15 drug can be rechallenged to see if that 16 adverse event reoccurs. 17 Q To your knowledge at any time has Lilly 18 considered a rechallenge study of people 19 who have become suicidal on Fluoxetine? 20 A I don't recall. 21 Q To your knowledge has Lilly ever considered 22 a rechallenge study on people who have 23 become violent and aggressive on 24 Fluoxetine? PAGE 130 1 A Not to my knowledge. 2 (Deposition Exhibit 12 was marked for 3 identification.) 4 A Okay. 5 Q Are you familiar with Exhibit 12? 6 A I've seen this first page, but I don't 7 recall seeing the rest of these pages. 8 Q Can you tell me what the first page is? 9 A It was part of a resourcing exercise on 10 prioritization of the work within medical 11 essentially separating out all the 12 compounds that we were working on into 13 three different buckets as they are labeled 14 here. 15 Q So with regard to Prozac, it's prioritizing 16 projects related to Prozac? 17 A As the Prozac projects appear on this list, 18 yes. 19 Q Okay. What is Sergolexole, 20 S-e-r-g-o-l-e-x-o-l-e? 21 A A compound that we had in development for 22 depression. 23 Q Is this a serotonin reuptake inhibitor as 24 far as you know? PAGE 131 1 A I don't know. 2 Q How about Quinelorane, 3 Q-u-i-n-e-l-o-r-a-n-e? 4 A Another compound that we had in development 5 within the CNS area. 6 Q What was that to be used for? 7 A I'm not sure if I should answer that. 8 MR. MYERS: Let me talk to her 9 for just a second. 10 MS. ZETTLER: Okay. 11 (A discussion was held off the record.) 12 MR. MYERS: She thinks it would 13 require her to reveal something 14 proprietary. I'm going to instruct her not 15 to answer. She's given a description of 16 what it is, a general description. 17 Q Is it a drug that is currently on the 18 market? 19 A No. 20 Q Has it been approved for marketing? 21 A No. 22 Q How about the other drug -- I'm not even 23 going to try to pronounce it again -- 24 Sergolexole? PAGE 132 1 A What about it? 2 Q Is that on the market? 3 A No. 4 Q Has it been approved? 5 A No. 6 Q Is it still being developed? 7 A I believe so. 8 Q Are all of these drugs listed in Exhibit 12 9 CNS drugs? 10 A What's listed here aren't all drugs. 11 Q What other types of things are listed? 12 A Well, if you look under the highly 13 questionable, things like Canadian Dose 14 Frequency, aging, metabolism, I have no 15 idea what those refer to. 16 Q Do you know what Canadian Turners means? 17 A Hormonic Growth Hormone study. Turners is 18 a deficiency in hormones. 19 Q How about in the first column under "Must 20 Do"? It says at the bottom "S-Nor - 21 depression - obesity". What does that 22 refer to? 23 A S-Nor is a synonym for a compound that we 24 had in development for those two PAGE 133 1 indications. 2 Q Is that S-Nor Fluoxetine? 3 A Yes. 4 Q Why is it that you felt comfortable telling 5 me that the Sergolexole was an 6 antidepressant, but you don't feel 7 comfortable in telling me what Quinelorane 8 is being used for? 9 MR. MYERS: You don't have to 10 answer that. 11 MS. ZETTLER: Why? 12 MR. MYERS: Because it had to 13 do with what she felt was proprietary and 14 not proprietary. There are obviously 15 compounds listed on that page other than 16 Fluoxetine. You're certainly entitled to 17 inquire about Fluoxetine. You may be 18 entitled to inquire generally about some 19 other things. 20 MS. ZETTLER: Well, Larry, 21 considering that none of these things have 22 been marked out, I think I at least can ask 23 some general questions about them. I'm not 24 going to ask her about any details, but I PAGE 134 1 think I have a right to ask her generally. 2 MR. MYERS: Apparently you got 3 to a level of detail that she is not 4 comfortable with. Whether they're marked 5 out or not, whether they should have been 6 marked out or not does not necessarily give 7 you free reign to inquire into compounds 8 other than the Fluoxetine. 9 MS. ZETTLER: I think you've 10 waived it. 11 MR. MYERS: Well, I don't think 12 we have. I think if there has been any 13 disclosure, it might have been 14 inadvertently, but all I'm saying is that 15 this lawsuit here is about Fluoxetine. 16 MS. ZETTLER: Which is a 17 serotonin reuptake inhibitor, and if either 18 of these other two are serotonin reuptake 19 inhibitors, I want to know. 20 MR. MYERS: She answered a 21 question as to one of them. 22 MS. ZETTLER: Right. And I 23 just want to know why she feels 24 uncomfortable about answering about PAGE 135 1 Quinelorane and she doesn't feel 2 uncomfortable about answering a question -- 3 which is a general question -- about 4 Sergolexole. 5 MR. MYERS: I'm not going to 6 let her answer that. 7 MS. ZETTLER: Certify it. 8 Q Are you aware that there were other drug 9 manufacturers out there in July of 1989 10 testing serotonin reuptake inhibitors for 11 use with obsessive-compulsive disorder? 12 A No. 13 Q What's a priority compound or an "A 14 Priority Compound"? 15 MR. MYERS: Are you looking at 16 something? 17 MS. ZETTLER: Page 1995. 18 A Again, that was a reference to a list that 19 would have been put together in a project 20 prioritization resourcing kind of 21 discussion. "A Priority" would have been 22 those compounds that were deemed to be the 23 most important akin to this "Must Do" list 24 on this first page. PAGE 136 1 Q So "A" category would be "Must Do", similar 2 to "Must Do"? 3 A Yes. 4 Q On the first page the highest priority 5 would be the "Must Do" and the least 6 highest priority out of those three would 7 be the "Highly Questionable"? 8 A That's how we would read this. 9 Q Who is Dr. Tsutomu Okimura, T-s-u-t-o-m-u, 10 O-k-i-m-u-r-a? 11 A He was an associate from our Japan office 12 who came to Lilly on an internship. He 13 spent some time in medical. He spent some 14 time in the basic research labs. 15 Q Did he go back to Japan? 16 A Yes, he did. 17 Q Did he work on Fluoxetine? 18 A No. 19 (Deposition Exhibit 13 was marked for 20 identification.) 21 Q Have you had a chance to review Exhibit 13? 22 A Yes. 23 Q Can you tell me what it is? 24 A I've not seen it before to my knowledge. PAGE 137 1 It looks like -- per its title -- 2 documentation for the host computer system. 3 Q Have you seen similar documents for other 4 indications other than obesity? 5 A Not that I recall. 6 (Deposition Exhibit 14 was marked for 7 identification.) 8 Q Do you recognize Exhibit 14? 9 A Yes. 10 Q Can you tell me what it is? 11 A A question was asked and this is the 12 response to that question. 13 Q What was the question? 14 A How many millions of characters of 15 information there are within a computer 16 system that has clinical trial data on it 17 in Europe. 18 Q Okay. What is "CTE"? 19 A I don't remember what the letters stand 20 for, but it was a clinical trial data 21 system in Europe. 22 Q And EMS? 23 A The same. EMS replaced CTE. 24 Q When it says 35 million characters, you PAGE 138 1 mean in the total database itself? 2 A I don't know. 3 Q Do you know why a question was asked? 4 A No, I don't. 5 Q Do you know who Kelly Westin is? 6 A Kelly Westin, no. 7 (Deposition Exhibit 15 was marked for 8 identification.) 9 Q Do you recognize Exhibit 15? 10 A I don't remember it. 11 Q Do you remember the project? 12 A No, I don't. 13 Q Do you recall whether or not you filled out 14 the questionnaire? 15 A I don't remember. 16 Q What did you do in preparation for 17 Dr. Beasley's meta-analysis article? 18 A I helped in coordinating and facilitating 19 the data gathering for that and I was 20 involved in a review of a preliminary draft 21 of the final manuscript, but that 22 manuscript was completed and submitted 23 after I went to England. 24 Q As far as the coordinating and gathering of PAGE 139 1 data in preparation for that article, was 2 that project different than the collection 3 of data for the review of the U.S. clinical 4 trial database? 5 A No, it was not. 6 Q Was the same data that was used? 7 A Yes. 8 Q The same procedure that was done as far as 9 collecting and analyzing the data we talked 10 about earlier? 11 A Yes. 12 Q To your knowledge did Lilly do any studies 13 or analyses on clinical trial data related 14 to suicidality prior to 1990? 15 A I don't recall. 16 (Deposition Exhibit 16 was marked for 17 identification and a discussion was held 18 off the record.) 19 Q Have you had a chance to review Exhibit 16? 20 A Yes, I have. 21 Q Do you recognize it? 22 A Yes. 23 Q Tell me what it is, please. 24 A It's a report that was prepared for the BGA PAGE 140 1 which is the German equivalence of the FDA 2 on suicide events related to suicide that 3 were known at the time that the report was 4 constructed. 5 Q And it was submitted to the BGA in December 6 of 1986; correct? 7 A Yes. 8 Q Why was it that you got a copy of this 9 report in August of 1990? 10 A I don't recall the specific reason. 11 Q Did you review this report in relation to 12 the O.U.S. data gathering project? 13 A I don't recall specifically. 14 Q Do you recall how many suicides were 15 determined to have been found from the 16 review of the O.U.S. data? 17 MR. MYERS: Completed suicides? 18 MS. ZETTLER: No. Yes, let's 19 start with completed suicides. 20 A No, I don't. 21 Q How about suicide gestures? 22 A No. 23 Q Was it more than a hundred total? 24 A I honestly don't know. PAGE 141 1 Q Do you know why this report was done that's 2 reflected in 16, was it done at the request 3 of the BGA? 4 A I don't know why it was done. 5 (Deposition Exhibit 17 was marked for 6 identification.) 7 Q Go ahead and take a look at 17. 8 A (Witness complies). Okay. 9 Q Do you recognize Exhibit 17? 10 A I don't remember it. 11 Q Were you a member of the Fluoxetine 12 cluster? 13 A Yes. 14 Q And if you look at the second page of the 15 exhibit, is that your signature at the 16 bottom? 17 A Yes, it is. 18 Q Does that indicate that you and Melissa 19 Humbert put this together? 20 A Yes. 21 Q Do you recall this meeting? 22 A No. 23 Q Do you recall what you meant at the bottom 24 of the first paragraph where it says "A PAGE 142 1 suggestion was made to print death forms, 2 much like pregnancy forms, that could be 3 forwarded to an investigator to capture 4 pertinent information if the death occurred 5 after the patient terminated from the 6 study"? 7 A Yes. 8 Q What does that mean? 9 A For pregnancy we initiated a program to 10 follow up on the mother as her pregnancy 11 continued and the birth of the baby and 12 follow the baby through its first two years 13 of life. And there were discussions around 14 whether we should have a similar program in 15 place to capture additional information on 16 patients who died after they discontinued 17 from our study. 18 Q Was that program put in place? 19 A Not to my knowledge. 20 Q Why not? 21 A The DEN system is a record of what happens 22 to a patient, and even after they terminate 23 from the study if an investigator gives us 24 additional information, it would be PAGE 143 1 collected in that DEN system. And I 2 believe the discussion I remember at the 3 time was that the DEN system for death 4 could serve as a way to capture the 5 information rather than putting another 6 system in place. 7 Q Okay. To your knowledge was there a system 8 put in place in which somebody who 9 discontinued from the study was followed 10 other than from after completing the study? 11 A No. 12 Q Why not, if you know? 13 A I don't know. 14 Q The "DE screens" referred to in the second 15 paragraph on the first page, is that data 16 entry screen? 17 A Yes. 18 Q What's the data entry screen? 19 A I think you called it the clinical trial 20 database. 21 Q Okay. So that those would be the data 22 entry screens that were created from the 23 individual case report forms? 24 A Yes. PAGE 144 1 Q On the second page it says at the top "The 2 following information was reviewed". 3 A Yes. 4 Q Under that there is seven -- looks like -- 5 points? 6 A Yes. 7 Q Okay. What's the second point mean where 8 it says "We must turn in our Travel Expense 9 Reports within two weeks of each trip", 10 what trips? 11 A CRAs frequently made trips out into the 12 field to visit the investigators' offices 13 or attend scientific meetings or conduct 14 start-up meetings. 15 Q Under No. 5 it says "HGH is conducting a 16 group start-up". What's HGH? 17 A Human growth hormone. 18 Q Under No. 6 it says "Dan Masica talked 19 about a part time position in conjunction 20 with Mary Huff of the legal component in 21 working through potential consumer product 22 liability issues." Do you know if issues 23 that were made were in regard to Fluoxetine 24 specifically? PAGE 145 1 A Not to my knowledge. 2 Q Why would the Fluoxetine cluster meeting be 3 discussing issues other than Fluoxetine? 4 A This is a report back from our department 5 head in attending a department head staff 6 meeting within the medical group and the 7 seven points listed here were points of 8 information that were shared with the whole 9 group so that information wasn't specific 10 to Fluoxetine wasn't shared with everyone 11 in the medical group. 12 Q What's SORT, S-O-R-T, at the bottom of the 13 page? 14 A I don't remember what the acronym stands 15 for. 16 Q Who is Joan Kuhlthau, Kuhlthau (phonetic)? 17 A She was a CRA within the CNS division. She 18 worked on other CNS compounds, but I don't 19 believe she worked on Fluoxetine. 20 Q Do you recall whether there were any deaths 21 that were discovered that had occurred 22 after patients terminated Fluoxetine 23 studies? 24 A In the trials that I worked on there were. PAGE 146 1 Q There were? 2 A They weren't discovered after. Patients 3 discontinued the clinical trial for 4 instance having suffered a myocardial 5 infarction. They were hospitalized and 6 discontinued from our trial, and at some 7 later point they may have died from that 8 and it would have been reported to us. 9 Q Which trials were those? 10 A The ones that I specifically worked on were 11 obesity studies. 12 Q And you remember specifically people having 13 died after terminating from obesity 14 studies? 15 A Yes. 16 Q How about bulimia studies? 17 A I don't recall. 18 Q Do you recall how many people died after 19 the obesity studies? 20 A No. 21 Q Was it more than one? 22 A Yes. 23 Q Have you ever discussed the issue of 24 suicidality and the use of Fluoxetine with PAGE 147 1 Dr. Leber? 2 A Personally, no. 3 Q Have you ever been present when he's had 4 discussions with other Lilly employees? 5 A Yes. 6 Q Can you tell me when? 7 A A September 1990 meeting at the FDA; that 8 was the topic of the meeting. 9 Q How about violent aggressive behavior, have 10 you ever been present when an FDA employee 11 has been discussing that subject with 12 Dr. Leber? 13 A No. 14 Q Have you ever discussed that subject with 15 Dr. Leber personally? 16 A No. 17 Q Have you ever discussed either of those 18 subjects with anybody from the FDA 19 personally? 20 A No. 21 Q Let's talk about the September 1990 meeting 22 for a few minutes. I believe you testified 23 earlier that you were in attendance at that 24 meeting; correct? PAGE 148 1 A Yes. 2 Q We know that the general subject matter of 3 the meeting was suicidality and the use of 4 Fluoxetine. 5 A (Affirmative nod). 6 Q Can you give me some details as to under 7 that broad category what was discussed? 8 A I don't remember the exact specifics of the 9 meeting. By that point in time we had done 10 an analysis of U.S. clinical trial database 11 and that was the substance of the 12 information that was shared with the FDA 13 and was discussed there. I don't remember 14 specific details. 15 Q Do you recall any clinical trials being 16 discussed at that -- other than a general 17 overview of clinical trials that had 18 already been performed -- do you remember 19 any clinical trials being discussed during 20 that meeting? 21 A I remember the discussion about a new 22 clinical trial as an option to gain more 23 information about the subject. 24 Q What was that new clinical trial to be, PAGE 149 1 what type of a trial? 2 A It was referred to earlier in the memo that 3 you had from Leigh Thompson in recounting 4 his conversation with Dr. Leber, the 5 prospective study on a large number of 6 patients that would be prescribed 7 Fluoxetine looking for the incidence of 8 suicide or related acts. 9 Q These were not necessarily people who had 10 become suicidal before while being on 11 Fluoxetine; correct? 12 A Correct. 13 Q Have you ever spoken with Dr. Martin 14 Teicher? 15 A No. 16 Q Have you ever been present when Dr. Teicher 17 has spoken to somebody else from Lilly? 18 A No. 19 Q Have you ever met Dr. Teicher? 20 A No. 21 Q Have you seen him at a seminar or an APA 22 meeting or anything of that nature? 23 A I don't think so. 24 Q How about Dr. Jonathan Cole? PAGE 150 1 A I've seen him give presentations at 2 scientific meetings, but I've not met him 3 personally. 4 Q Scientific meetings at Lilly? 5 A No. 6 Q Where? Association meetings, things of 7 that nature? 8 A Yes. 9 Q Have you ever seen Dr. Cole give a 10 presentation on depression? 11 A I don't recall the subject matter. 12 Q Have you worked with Dr. Cole as a clinical 13 investigator on any Fluoxetine trials? 14 A No. 15 Q I want to make sure that I wasn't confused 16 earlier when we were talking about the 17 manual review of the early clinical report 18 forms from the United States, okay? 19 A Okay. 20 Q Were those reviewed because they weren't on 21 computer at all? 22 A All of the data in the data collection 23 fields were on the computer. Any 24 handwritten comments outside of those data PAGE 151 1 captured fields that the investigator may 2 have jotted down in a note kind of way on a 3 case report form would not have been 4 included in the database in the clinical -- 5 in the clinical computer trial database. 6 Q And then at some point it became Lilly's 7 practice to record comments, also? 8 A Yes. Yes. 9 Q Why was that change in policy made? 10 A I don't know. 11 Q Do you know when it was made? 12 A No. 13 Q Was it before you became department head? 14 A Yes. 15 Q Was it before you became a CRA? 16 A Yes. 17 (Deposition Exhibit 18 was marked for 18 identification.) 19 A Okay. 20 Q Are you familiar with Exhibit 18? 21 A I'm familiar with the content. I don't 22 remember seeing this document. 23 Q Fourth paragraph down it says "I brought up 24 the possibility of us Xeroxing a copy of PAGE 152 1 the enclosure with the June 7, 1988 2 submission (MAOI)". Do you see that? 3 A Yes. 4 Q What is the June 7th, 1988 MAOI submission? 5 A I don't know specifically what they are 6 referring to here as the actual document 7 that was submitted to the FDA. 8 Q Was MAOI inhibitors discussed at the 9 September 25th, 1990 meeting? 10 A Not that I recall. 11 (Deposition Exhibit 19 was marked for 12 identification.) 13 A Okay. 14 Q Are you familiar with this document? 15 A No, I don't recall seeing it before. 16 Q Does it refresh your recollection as to 17 what was discussed at the September 25th, 18 1990 meeting? 19 A Not in any other detail than I've already 20 given you. 21 Q Under Point B it says "An in-hospital 22 rechallenge of patients who met predefined 23 criteria for suicidal acts or ideation on 24 either Fluoxetine or a standard tricyclic PAGE 153 1 antidepressant." Do you recall that 2 subject being discussed at the meeting? 3 A No. 4 Q To your knowledge were there discussions 5 between Lilly employees and Dr. Teicher on 6 Dr. Teicher's cooperation on any 7 prospective study or rechallenge study on 8 Fluoxetine? 9 A I don't recall. 10 Q This appears to be meeting minutes written 11 by the FDA, does it not? 12 A I can't tell who wrote this. 13 Q Is this a form that meeting minutes were 14 usually written up at Lilly? 15 A I don't know. 16 Q Are you familiar with the phrase "A Prozac 17 Safety Team"? 18 A No. 19 (Deposition Exhibit 20 was marked for 20 identification.) 21 A Okay. 22 Q Do you recognize Exhibit 20? 23 A No, I don't. 24 Q On the last page of the exhibit it has the PAGE 154 1 words "Prozac Safety Packet, Assignments" 2 listed at the top. Do you see that? 3 A Yes. 4 Q To your knowledge is the Laura mentioned on 5 the right-hand side of the page you? 6 A Yes. 7 Q Do you recall being given those 8 assignments? 9 A Yes. 10 Q What did you do with regards to hostility 11 and violence in preparation for the safety 12 packet? 13 A The attachments were the specific data 14 analyses or data printouts from our 15 clinical trial computer database. I would 16 have assembled those and put them in with 17 the rest of this packet for the FDA. 18 Q Would that be the same for suicide? 19 A Yes. 20 Q Anything else that you would have done with 21 regards to violence -- hostility, violence 22 or suicide? 23 A No. 24 Q At the bottom it says "CT Databases", and I PAGE 155 1 believe your name is listed again after 2 that. 3 A Yes. 4 Q Was your assignment with regards to the 5 clinical trial databases any different than 6 the ones listed above? 7 A I don't recall what the specific assignment 8 was there. 9 (Deposition Exhibit 21 was marked for 10 identification.) 11 A Okay. 12 Q Do you recognize this document? 13 A I don't remember this specific document. 14 Q Are you familiar with the project discussed 15 in the document? 16 A Yes, I am. 17 Q Can you describe that project for me? 18 A There were a number of topics of interest 19 listed here under the column "Topics" 20 related to Fluoxetine. Jim Kotsanos -- the 21 author of this particular memo -- is a 22 pharmacoepidemiologist, and he led a group 23 whose names are under "Assignment" who were 24 responsible for reviewing each of those PAGE 156 1 topics in relation to Fluoxetine. 2 Q When you say that they were responsible for 3 reviewing each of those topics, what do you 4 mean? 5 A Working with our systems analysts and 6 statisticians and physicians to pull out 7 any related information within the 8 Fluoxetine clinical trial database related 9 to those topics. 10 Q Did you have a role in this project? 11 A No, I didn't. 12 Q Were some of the people listed under the 13 assignment portion of this memo people that 14 worked underneath you? 15 A Four of them worked under me. 16 Q Did you have any responsibilities to make 17 sure that those people that worked under 18 you completed their assignments? 19 A It's difficult for me to remember. This 20 was around the time that I transitioned to 21 my new job and I either had that 22 responsibility or the person who replaced 23 me. 24 Q Do you know if this project then had been PAGE 157 1 completed? 2 A To my knowledge it was not complete when I 3 went to my new assignment. 4 Q When did you go to your new assignment 5 again? 6 A Around Thanksgiving time mid to end 7 November. 8 MS. ZETTLER: Do you want to 9 take a break? 10 MR. MYERS: Sure, that would be 11 fine. 12 (A brief recess was taken and 13 Deposition Exhibit 22 was marked for 14 identification.) 15 A Okay. 16 Q Do you recognize Exhibit 22? 17 A I'm familiar with the content. I don't 18 remember the specific document. 19 Q Can you tell me what the subject was 20 generally? 21 A Changing from the ELECT dictionary to the 22 COSTART dictionary at Lilly. 23 Q I'm sorry, what was the last part? 24 A At Lilly. PAGE 158 1 Q At Lilly, okay. To your knowledge did this 2 change actually take place? 3 A To my knowledge it did. 4 Q What prompted the change? 5 A I don't recall. 6 Q Were the terms that were added to the 7 FDA -- to the COSTART dictionary added to 8 the ELECT dictionary? 9 MR. MYERS: At what point in 10 time? 11 MS. ZETTLER: As a result of 12 this meeting. 13 MR. MYERS: Okay. 14 A I don't remember the details. The contents 15 of this indicates there were a number of 16 terms deleted and a number of terms added. 17 Q But you don't recall if the terms that were 18 deleted or added -- deleted from or added 19 to COSTART by the FDA were in turn deleted 20 from or added to ELECT by Lilly? 21 A I think I'm misunderstanding your question. 22 Q I'm just trying to find out what happened 23 as a result of the FDA's change in the 24 COSTART dictionary if anything at Lilly? PAGE 159 1 A Okay. We looked in our ELECT dictionary to 2 see how it differed from the FDA COSTART 3 dictionary, and the changes were made to 4 make it consistent with COSTART whether 5 that meant adding or deleting. 6 Q To your knowledge was the ELECT dictionary 7 meant to track the COSTART dictionary? 8 A I don't know. 9 Q Do you know why it was that Lilly just 10 didn't use the COSTART dictionary as it 11 existed? 12 A No. It was already in place when I became 13 a CRA. 14 Q Do you recall having to change CRFs as a 15 result of the changes made to the ELECT 16 dictionary? 17 A No. 18 Q Do you recall that that did not happen? 19 A I don't recall myself actually making 20 changes on case report forms of adverse 21 event terms. 22 Q Do you recall whether or not databases were 23 changed as a result of the changes in the 24 COSTART dictionary? PAGE 160 1 A I don't remember. 2 (Deposition Exhibit 23 was marked for 3 identification.) 4 A Okay. 5 Q Do you recognize Exhibit 23? 6 A No, I've not seen it before that I recall. 7 Q You were in Erl Wood in April of '91; 8 correct? 9 A Yes. 10 Q Do you know why you would have been copied 11 or listed as a recipient in this E-mail 12 that is on the first page of the exhibit? 13 A The first page because it has to do with 14 O.U.S. depression trials, so I imagine that 15 for my information it was forwarded to me. 16 Q When it says here "during a comparison of 17 the CRFs to the DEN system", would those 18 have been the CRFs that were collected as 19 part of the data gathering project? 20 A I don't know for certain. 21 Q The second and third pages of the exhibit 22 appear to be E-mails talking about deaths 23 that are reported in the DEN system; 24 correct? PAGE 161 1 A Yes. 2 Q Were a review of the numbers of deaths that 3 were reported in the DEN system done on a 4 regular basis or was that done in 5 preparation for any of the projects you 6 were talking about earlier? 7 A They were done on a regular basis. 8 Q How often? 9 A At minimum they were done quarterly because 10 in the Code of Federal Regulations once a 11 compound has been approved, for the first 12 three years of its life on the market there 13 is a requirement to supply quarterly 14 updates to the FDA, and an analysis or a 15 review of all of the deaths that had 16 occurred would have been part of that 17 review. 18 Q Now, when it says here total -- let's see, 19 strike that. The deaths that are talked 20 about here in the trials, those are not 21 just double-blind controlled study trials; 22 correct? 23 A No. DEN captures both clinical trial 24 reports and spontaneous reports from PAGE 162 1 physicians treating their patients. 2 (Deposition Exhibit 24 was marked for 3 identification.) 4 A Okay. 5 Q Do you recognize Exhibit 24? 6 A Yes. 7 Q What is Page 1 of Exhibit 24? 8 A A summary of the number of events, adverse 9 events for 1989 that were reported. 10 Q Okay. So where it says under "Total Events 11 5,973", would that be the total number of 12 events for 1989? 13 A I believe so. 14 Q And for that year there were 5,633 15 spontaneous adverse events reported and 340 16 clinical trial adverse events reported? 17 MR. MYERS: In DEN? 18 MS. ZETTLER: In DEN. 19 A This memo doesn't refer specifically to 20 DEN, so I can't be sure. 21 Q Well, the serious adverse events should be 22 reported in the DEN system; correct? 23 A Yes, they should, right. 24 Q And towards the bottom of the page it says PAGE 163 1 non-serious? 2 A Right. 3 Q 4,912? 4 A Yes. 5 Q So does that indicate to you that in the 6 DEN system there were 5,973 adverse events 7 reported total for that year? 8 A Yes. 9 Q And 4,912 non-serious adverse events for 10 that year? 11 MR. MYERS: As a subset of the 12 50 some hundred -- 13 THE WITNESS: Of the total. 14 MR. MYERS: -- or as a separate 15 number? I don't know what your question 16 is. 17 MS. ZETTLER: As a separate 18 number. 19 Q Or is that -- 20 A To me it looks like the 4,912 is a subset 21 of the 5,973. 22 Q Okay. So what they're saying here is -- 23 well, now I'm confused. If there were 24 5,633 spontaneous adverse events reported, PAGE 164 1 is this memo saying that out of those 5,633 2 that 4,864 were deemed to be non-serious? 3 A Yes, that's what this is saying. 4 Q How was it determined that 4,864 5 spontaneous adverse events were 6 non-serious? 7 A I don't know. 8 Q The next page talks about deaths in 9 clinical trials; correct? 10 A Yes. 11 Q And it says as of July 24th, 1990, there 12 were a total of 60 deaths, 29 of which were 13 suicides; correct? 14 A Yes. 15 Q Would these be deaths reported in 16 Fluoxetine clinical trials or clinical 17 trials for all Lilly drugs? 18 A Fluoxetine from this memo. 19 Q Let's go back to Exhibit 23 the second 20 page. These are Prozac deaths reported in 21 DEN as of October 26, 1990; correct? 22 A Which ones, the ones in Exhibit 23? 23 Q Yes, the second page. 24 A Yes. PAGE 165 1 Q Okay. And as of October 26, 1990, there 2 were 168 suicide deaths reported in DEN 3 generally; correct? 4 A Yes. 5 Q This doesn't break it down into clinical 6 trials as opposed to spontaneous, does it? 7 A No, it does not. 8 Q Do you know if there was a similar analysis 9 of how many deaths had occurred during 10 clinical trials as of October 26, 1990? 11 A I don't know. 12 Q On the last page of Exhibit 24 can you tell 13 me what that is? 14 A Yes. This is a letter from another 15 pharmaceutical company that was actually 16 forwarded to me while I was in the UK. The 17 other pharmaceutical company's drug is 18 Inderal which is mentioned in the content 19 of this letter, and the patient was taking 20 both Prozac and Inderal and had an adverse 21 event. Because Prozac was involved a copy 22 was forwarded to Lilly. 23 Q In your experience at Lilly have you seen 24 other instances where other drug companies PAGE 166 1 have reported adverse events to Lilly? 2 A Yes. 3 Q On how many occasions? 4 A That I think I recall specifically -- 5 Q Yes. 6 A -- one or two. 7 Q In your experience at Lilly has Lilly 8 reported adverse events occurring on drugs 9 manufactured by other companies to those 10 companies? 11 A I don't know. 12 Q Have you ever done that? 13 A No. 14 Q If somebody was participating in a 15 Fluoxetine comparator study and they 16 suffered an adverse event while being 17 randomized to a drug other than Fluoxetine 18 or placebo, was it Lilly's practice to 19 contact the drug company and alert them 20 that somebody who had been on the study had 21 suffered an adverse event? 22 A I did not personally work on any of those 23 clinical trials and I don't know what the 24 process was for those who did. PAGE 167 1 Q On the obesity, bulimia and smoking trials 2 that you worked on were any of those 3 comparator studies? 4 A No, they were not. 5 Q Is there a requirement by the FDA to your 6 knowledge that manufacturers report adverse 7 events to other manufacturers that occur on 8 drugs? 9 A Not to my knowledge. 10 (Deposition Exhibit 25 was marked for 11 identification.) 12 A Okay. 13 Q Do you recognize Exhibit 25? 14 A No, I've not seen it before. 15 Q To your knowledge did Lilly ask outside 16 consultants or outside -- strike that. To 17 your knowledge did Lilly ask people outside 18 of Lilly to comment or represent Lilly in 19 the media regarding Fluoxetine? 20 A I don't recall. 21 Q Do you know who Dr. David Dunner is? 22 A Yes. 23 Q Who is Dr. Dunner? 24 A One of the investigators that we've used PAGE 168 1 within our area. I recall him working on 2 another drug, not Fluoxetine. 3 Q What other drug? 4 MR. MYERS: Don't. Is it 5 marketed? 6 THE WITNESS: No, it is not. 7 MR. MYERS: Don't tell her what 8 it is. 9 Q Has he worked on any other drugs besides 10 the drug you're thinking of and Fluoxetine? 11 A Not for Lilly. 12 Q Is he a psychiatrist? 13 A Yes, he is. 14 Q To your knowledge did he perform more than 15 one trial on Fluoxetine for Lilly? 16 A I don't know. 17 Q Did he perform more than one trial for 18 Lilly on the other drug? 19 A Only one that I'm aware of. 20 (Deposition Exhibit 26 was marked for 21 identification.) 22 A Okay. 23 Q Do you recognize Exhibit 26? 24 A No, I don't remember this. PAGE 169 1 Q Do you recognize the names of any of the 2 rating scales that are listed on the second 3 page of Exhibit 26? 4 A Yes, we've used some of these. 5 Q Which ones? 6 A The CGI. 7 Q Okay. 8 A COVI. 9 Q Okay. 10 A HAM-A, HAM-D, the MADRS, PGI and RASKIN. 11 Q Are you familiar with any of the other 12 scales? 13 A I recognize the names, but I don't recall 14 the scales. 15 Q To your knowledge has Lilly ever considered 16 using any of these other scales like the 17 Agitation Rating Scale or the Adult 18 Suicidal Ideation Questionnaire? 19 A I don't know. 20 (Deposition Exhibit 27 was marked for 21 identification.) 22 A Okay. 23 Q Do you recognize this exhibit? 24 A No, I don't remember this. PAGE 170 1 Q Do you recall a meeting being held on 2 November 28, 1990 at the Omni here in 3 Indianapolis? 4 A I do not. 5 Q In a typical start-up meeting on a clinical 6 trial would these people have attended the 7 meeting, such a meeting? 8 A It would depend on the size of the study 9 and the number of investigators involved. 10 Q Have you ever been involved in a start-up 11 meeting where this many people from Lilly 12 attended? 13 A Yes. 14 Q In what situation? Was it a Fluoxetine 15 trial? 16 A One was. 17 Q On what trial? 18 A Our obsessive-compulsive disorder study. 19 Q On the last page of the exhibit it lists a 20 Jim Pedinski from Smith-Kline-Beechman and 21 a Dawn Prisciotta also from Smith-Kline. 22 A Yes. 23 Q Do you see that? 24 A Yes. PAGE 171 1 Q Why would people from Smith-Kline-Beechman 2 be at an investigator meeting for Lilly? 3 A Probably because we used their laboratory 4 facilities for the laboratory analyses from 5 the patients in the clinical trial. 6 Q Does this represent the start-up meeting on 7 the OCD meeting or the OCD trial? 8 A No. 9 Q You're listed as an attendee on here. Do 10 you recall attending that meeting? 11 A No, I do not. 12 Q Would you have been in England by this 13 time, November 28th, 1990? 14 A I may have been. 15 Q I'm sorry. Can you look at that one real 16 quickly again (indicating). There are no 17 clinical investigators listed on this 18 exhibit, are there? 19 A No. 20 (Deposition Exhibit 28 was marked for 21 identification.) 22 A Okay. 23 Q Do you recognize this exhibit? 24 A No, I do not. PAGE 172 1 Q Do you know who Leandro Herrero is? 2 A At the time he was a Lilly physician within 3 the Indianapolis medical group. 4 Q And where is he now? 5 A He's left the company. 6 Q Do you know where he lives? 7 A No, I don't. 8 Q How about Professor Leonard, B. E. Leonard? 9 A Don't know him. 10 Q To your knowledge is he a Lilly employee? 11 A I don't know. 12 Q Do you know if these reports from the 13 consultants were taken into consideration 14 in structuring the analysis of the O.U.S. 15 data? 16 A I don't know. 17 Q Have you ever heard of a John Henry? 18 A No. 19 Q If you look at the second to the last page 20 of the exhibit -- I'm sorry the third to 21 the last page, 2382 in the lower right-hand 22 corner. 23 A Okay. 24 Q Do you know who Claude Bouchy is? PAGE 173 1 A No, I do not. 2 Q How about any of the people listed at the 3 top of the E-mail? 4 A Walter Lange has retired from the company, 5 but he used to be in the marketing side of 6 our business. Gerhard Mayr is -- I don't 7 recall his exact title, but he's the head 8 of Lilly's European operations. Sidney 9 Taurel is in Indianapolis also in senior -- 10 a senior management position. Allan 11 Weinstein is a vice-president within the 12 medical group. 13 Q Is it your understanding that at one point 14 Prozac was not allowed on the market in 15 Austria? 16 A I don't know. 17 Q How about Germany? 18 A I don't know. 19 Q Did you have any responsibility or do you 20 have any responsibility for registration of 21 Fluoxetine in countries outside of the 22 United States? 23 A No, I don't. There is a separate 24 registration group that handles that. PAGE 174 1 Q Other than what we talked about earlier, 2 did you have any other responsibilities 3 with regards to Fluoxetine and the issue of 4 suicidality? 5 A Not to my knowledge. 6 Q Other than what we talked about earlier, 7 did you have any other responsibilities 8 with regards to Fluoxetine and violent 9 aggressive behavior? 10 A No. 11 Q Did you have any responsibilities regarding 12 the use of Fluoxetine in tardivedyskinesia? 13 A No. 14 Q How about the use of Fluoxetine in movement 15 disorders? 16 A No. 17 MS. ZETTLER: Okay. That's all 18 I have. Thanks. 19 MR. MYERS: Thank you. 20 THE WITNESS: Thank you. 21 AND FURTHER THE DEPONENT SAITH NOT. 22 23 ---------------------------- 24 LAURA A. FLUDZINSKI PAGE 175 1 STATE OF INDIANA ) ) SS: 2 COUNTY OF MARION ) 3 I, Linda M. Bour, a Notary Public in 4 and for the County of Marion, State of 5 Indiana at large, do hereby certify that 6 LAURA A. FLUDZINSKI, the deponent herein, 7 was by me first duly sworn to tell the 8 truth, the whole truth, and nothing but the 9 truth in the aforementioned matter; 10 That the foregoing deposition was 11 taken at the offices of Baker & Daniels, 12 320 North Meridian Street, Suite 2700, 13 Indianapolis, Marion County, Indiana, on 14 the 28th day of October 1993, commencing at 15 the hour of 9:05 a.m., pursuant to the 16 applicable Rules of Civil Procedure; 17 That said deposition was taken down 18 in stenograph notes and afterwards reduced 19 to typewriting under my direction, and that 20 the typewritten transcript is a true record 21 of the testimony given by said deponent; 22 and thereafter presented to said deponent 23 for her signature; 24 That the parties were represented by PAGE 176 1 their aforementioned counsel. 2 I do further certify that I am a 3 disinterested person in this cause of 4 action; that I am not a relative or 5 attorney of either party, or otherwise 6 interested in the event of this action, and 7 am not in the employ of the attorneys for 8 either party. 9 IN WITNESS WHEREOF, I have hereunto 10 set my hand and affixed my notarial seal 11 this _____ day of ___________, 1993. 12 13 ___________________________ N O T A R Y P U B L I C 14 My Commission Expires: 15 June 19, 1996 16 County of Residence: Marion 17 PAGE 177