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 continued deposition upon oral examination of CATHERINE H. MESNER, 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 15th day of October 1993, pursuant to notice in accordance with the Civil Rules of Procedure. (VOLUME II) 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 KIMBERLY A. WILKINS 12 COUNSEL FOR DEFENDANTS CZECHOWICZ, FINK, BRUINS, CLAUSEN, MILLER, GORMAN, CAFFREY & WITOUS 13 10 SOUTH LaSALLE CHICAGO, ILLINOIS 60603 14 PAUL J. CLEMENTI 15 COUNSEL FOR DR. DICKIE KAY HINSHAW & CULBERTSON 16 222 NORTH LaSALLE STREET SUITE 300 17 CHICAGO, ILLINOIS 60601-1081 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 (Continuing).............. 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.: (Continued) 8 EXHIBIT 10................................... 19 9 EXHIBIT 11................................... 28 10 EXHIBIT 12................................... 74 EXHIBIT 13................................... 110 11 EXHIBIT 14................................... 127 EXHIBIT 15................................... 132 12 EXHIBIT 16................................... 137 13 EXHIBIT 17................................... 139 EXHIBIT 18................................... 146 14 EXHIBIT 19................................... 149 EXHIBIT 20................................... 152 15 EXHIBIT 21................................... 154 16 EXHIBIT 22................................... 155 EXHIBIT 23................................... 158 17 EXHIBIT 24................................... 161 EXHIBIT 25................................... 164 18 EXHIBIT 26................................... 165 19 EXHIBIT 27................................... 169 EXHIBIT 28................................... 170 20 EXHIBIT 29................................... 183 EXHIBIT 30................................... 186 Page 3 1 C A T H E R I N E H. M E S N E R, 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 (Continuing), 7 QUESTIONS BY NANCY ZETTLER: 8 Q Hi, Catherine. 9 A Hi. 10 Q Welcome back. Do you understand that all the 11 ground rules that we talked about last time are 12 the same this time? 13 A Yes. 14 Q Do you need me to go over them? Do you want me 15 to refresh your memory on that? 16 A No. 17 Q Is there any reason why you are not going to be 18 able to testify today such as taking 19 medications or anything of that nature? 20 A No. 21 MR. CLEMENTI: Nancy, before we 22 start, if I could say something on the record. 23 MS. ZETTLER: Sure. 24 MR. CLEMENTI: There was some Page 4 1 confusion as to whether these depositions were 2 cross-noticed or not, as to whether they were 3 going or not. One of the codefendants was told 4 that this deposition was not going. I am 5 placing on the record this objection to any 6 continuing of the confusion and mistakes in 7 cross-noticing just so there is notice that 8 there has been this confusion. Why don't we go 9 ahead. 10 MR. MYERS: Okay. My understanding 11 is that these were scheduled though not noticed 12 in the Fentress case. I don't know that there 13 is a notice in Fentress. They were 14 cross-noticed nonetheless in the MDL. I do not 15 believe they were cross-noticed in at least the 16 Chicago state court cases, but I could be 17 wrong. But we will nonetheless endeavor -- 18 MR. CLEMENTI: And that is the 19 exact problem. We'd like to try to find out 20 when they're noticed for who and what and then 21 have one place to go to. 22 MR. MYERS: I understand. 23 MR. CLEMENTI: Thank you. 24 MS. ZETTLER: You can always call Page 5 1 me, Paul. 2 MR. CLEMENTI: Which I'm going to 3 continue to do, Nancy. 4 Q Catherine, you understand that you are under 5 oath; right? 6 A Yes. 7 Q And you understand that that means that you've 8 sworn to tell the truth; correct? 9 A Yes. 10 Q Let's go back to the outside the U.S. data 11 gathering project that you participated in. I 12 believe it was in 1991. 13 A That's incorrect. 14 Q Okay. When was that when you went over to 15 Europe? 16 A 1990. 17 Q In 1990, okay. I'm sorry. And I believe you 18 said the decision to collect the outside the 19 U.S. data or O.U.S. -- can we use O.U.S.? 20 A Yes. 21 Q -- was made in September of '90? 22 A Yes. 23 Q Do you remember when you went over to Europe? 24 A October '90. Page 6 1 Q Have you reviewed any documents in preparation 2 for the continuation of your deposition today? 3 A Yes. 4 Q What documents have you reviewed? 5 A Just last time's testimony. 6 Q Oh, the transcript from last time? 7 A Yes. 8 Q Well, then before we move on, have you had the 9 chance to read the entire transcript? 10 A No. 11 Q How much of it have you read? 12 A Three-quarters. 13 Q Did you want to make any changes to any of the 14 answers that you gave last time? 15 A No. 16 Q Is there anything that you want to change as 17 far as substantively in the deposition, things 18 that you testified to? 19 A No. 20 Q When do you plan on completing your reading of 21 the deposition transcript? 22 A I had read it once completely. Just in 23 reviewing now I just read three-quarters of it. 24 Q So in preparation for today you read Page 7 1 three-quarters of it? 2 A (Affirmative nod). 3 Q Yes? You have to say yes or no. 4 A Yes. 5 Q Okay. Any other documents that you reviewed in 6 preparation for today? 7 A No. 8 Q Any documents that you have reviewed related to 9 Fluoxetine between the first portion of your 10 deposition and today? 11 A No. 12 Q Anything that you've reviewed, any documents 13 related to suicidality or depression? 14 A No. 15 Q I take it your answers with regards to the 16 first three-quarters of the deposition that you 17 had no exceptions and didn't want to change any 18 of your answers holds true for the entire 19 deposition from last time? 20 A Yes. 21 Q How did you get over to Europe when you went 22 over there to work on the O.U.S. data 23 collection project? 24 A In an airplane. Page 8 1 Q Was that a commercial flight? 2 A Yes. 3 Q Which airline? 4 A Delta. 5 Q Did some of your co-workers fly over there in 6 the Lilly corporate jet? 7 A Yes. 8 Q How come you weren't allowed to fly on the 9 corporate jet with them? 10 A There were not enough seats on the corporate 11 jet. 12 Q Can you give me the names of some of the other 13 people that went over to Europe with you on 14 that project, people from Indianapolis? 15 A Sharon Essington, Lisa DeVault, Carole Dellova. 16 Q Could you spell that name, please. 17 A Carole, with an e, and D-e-l-l-o-v-a. 18 Q Okay. Anybody else? 19 A Joye Schmiedt. 20 Q Anybody else? 21 A Velva Brewer. 22 Q I'm sorry, what was the first name? 23 A Velva. 24 Q V-e-l-v-a? Page 9 1 A Yes. 2 Q Brewer was her last name? 3 A Yes. 4 Q Anybody else? 5 A Rita Root. 6 Q Could you spell her last name? 7 A R-o-o-t. 8 Q Anyone else? 9 A Heather Campbell. 10 Q Anyone else? 11 A That's about all I can remember. 12 Q Anybody from management go over there with you? 13 A No. 14 Q Who is Gordon Gilad, G-i-l-a-d? 15 A He was a physician. 16 Q Did he go? 17 A I think he lived in Europe at that time. 18 Q Did he work out of one of the European 19 affiliates? 20 A Yes. 21 Q When you say he's a physician, was he a 22 psychiatrist? 23 A I don't know what his specialty was. 24 Q Did he work on the O.U.S. data collection Page 10 1 project? 2 A Initially he worked with me on that project. 3 Q What did he do with you? What was your role 4 working together? 5 A He was a physician consultant as I reviewed 6 protocols. 7 Q For this project? 8 A Yes. 9 Q Was there a protocol written for the data 10 collection project? 11 A No. 12 Q When you say you reviewed protocols, what did 13 you mean? 14 A The protocols which would be involved -- all 15 the European protocols or O.U.S. protocols that 16 were reviewed, he assisted in reviewing. 17 Q The O.U.S. protocols for the studies from which 18 you were going to be collecting data? 19 A Yes. 20 Q How many protocols did you review in 21 preparation for that project? 22 A All protocols. 23 Q All O.U.S. protocols? 24 A Yes. Page 11 1 Q What was the purpose for reviewing the 2 protocols? 3 A To decide if they met the criteria. 4 Q You said you and Dr. Gilad -- is that Gilad? 5 Is that how you say it? 6 A Yes. 7 Q Did anybody else review protocols in 8 preparation for this project, the O.U.S. data 9 collection project? 10 A I don't think so. 11 Q I'm sorry, you said you were reviewing them to 12 decide if they met criteria? 13 A Yes. 14 Q What criteria would that be? Is that -- 15 A Were they depression-related protocols. 16 Q Any other? 17 A If they were double-blinded protocols. 18 Q Any others? 19 A If in fact they were protocols that were 20 performed. 21 Q Any others? 22 A To just assure there were no duplications. 23 Q When you say the criteria, is this the criteria 24 that was used to determine whether or not the Page 12 1 individual study would be included in the data 2 collection process? 3 A Yes. 4 Q Who came up with that criteria? 5 A I don't remember. 6 Q Dr. Beasley? 7 A My recollection is that they were going to 8 follow the same criteria that was used in the 9 U.S. 10 Q I believe the testimony last time was that not 11 all of the double-blind controlled studies that 12 were performed outside the U.S. were included 13 in the data collection process; is that 14 correct? 15 MR. MYERS: Can you show her where 16 she said that. 17 MS. ZETTLER: You asked me that, 18 Larry, on the one page I didn't write down. 19 MR. MYERS: I'm going to help you. 20 MS. ZETTLER: Thanks. 21 MR. MYERS: Look at Page 220 22 starting at Line 22 and then go over to 23 Page 221. 24 MS. ZETTLER: Okay. Page 13 1 MR. MYERS: I don't know if that's 2 it or not, but that addresses the subject. 3 Q Let me ask it this way: Is it your 4 recollection that there were like 46 5 double-blind studies included in that project? 6 A Thereabouts. 7 Q Okay. And all of those studies were 8 double-blind controlled studies; correct? 9 A Yes. 10 Q Look on Page 217. 11 A (Witness complies). 12 MR. MYERS: At what, where it says 13 how many studies were involved? 14 MS. ZETTLER: Towards the bottom of 15 the page, Line 21, starts approximately 48. 16 MR. MYERS: Right. 17 MS. ZETTLER: And then I asked how 18 many trials were conducted on Fluoxetine 19 worldwide not limiting it to double-blind 20 controlled. 21 MR. MYERS: Right. 22 Q You said you didn't know. 23 A (Affirmative nod). 24 Q Do you know if in that 48 or did that 48 Page 14 1 include all double-blind controlled studies 2 that were performed outside the United States? 3 A For depression? 4 Q Sure, you can limit it to depression. 5 A To the best of our knowledge, yes. 6 Q When you say "the best of our knowledge", what 7 do you mean? I'm interested in the best of 8 your knowledge, Catherine. 9 A Best of my knowledge, yes. 10 Q There were other double-blind controlled 11 studies for other indications that were not 12 included in that data collection process? 13 A Yes. 14 Q Do you know why those other double-blind 15 controlled studies were excluded for the other 16 indications? 17 A I believe it was because we were trying to do 18 the same analysis that was done on the U.S. 19 data which was limited to depression. 20 Q Do you know why the U.S. data collection 21 analysis or data analysis was limited to 22 depression? 23 A No, I do not. 24 Q Do you know who made that decision to limit the Page 15 1 analysis to depression? 2 A No. 3 Q My understanding of what you guys did when you 4 went over to Europe was to review the case 5 report forms for the various studies and 6 collect data from each of those forms; correct? 7 A Yes. 8 Q Can you give me a general idea of what type of 9 data you collected from those forms? 10 A Safety information. 11 Q Anything else? 12 A Efficacy information. 13 Q Anything else? 14 A Historical information. 15 Q When you say historical, do you mean patient 16 history? 17 A Yes. 18 Q Anything else? 19 A That seems to encompass the bulk of the study. 20 Q Were you excluding information that had been 21 collected on the case report forms; in other 22 words, did you go over there and just pull 23 certain information from the case report forms 24 generally like demographic or history-type Page 16 1 information and leave other information, not 2 collect other information? 3 A We did not collect every piece of information 4 from every trial. No, we didn't. We did 5 exclude, but not in terms of limiting it to 6 safety or -- in other words, we collected 7 everything in regards to safety. 8 Q Give me an idea of what types of information 9 you considered safety information as part of 10 this project. 11 A Adverse event information. 12 Q Anything else? 13 A Historical information. 14 Q For instance, if they had prior suicide 15 attempts before being included in the study? 16 A Yes. 17 Q Was this information gathered with an eye 18 towards investigating the incidence of 19 suicidality in the patients? 20 A Yes. 21 Q When you say adverse event information, did you 22 worry about information such as rashes and 23 things of that nature? 24 A Yes. Page 17 1 Q All adverse event information was taken down? 2 A All safety information was taken down. 3 Q Besides adverse event information and history, 4 what other safety information was collected? 5 A Secondary illness. 6 Q What do you mean by secondary illness? 7 A Illnesses that were ongoing or concurrent 8 during the time of the study. 9 Q Including the indication illness, in other 10 words, depression? 11 A No. 12 Q When you say depression, were the studies 13 limited to a certain type of depression; for 14 instance, major depressive disorder as opposed 15 to bipolar or some other depression-related 16 illness? 17 A All depression illness is included. 18 Q Did it make a difference as to whether or not 19 the study called for the patients to be 20 inpatients or outpatients? 21 A No. 22 Q So when you say secondary illness information 23 was collected, say if the person was suffering 24 from tuberculosis as well as depression, the Page 18 1 tuberculosis would be recorded? 2 A Yes. 3 Q Was a special form created to be used? 4 A Yes. 5 Q Who created that form? 6 A I did with some assistance. 7 Q What was that form called? 8 A A work sheet. 9 MS. ZETTLER: Let's mark this. 10 MR. MYERS: Do you want to just 11 continue with the numbers? 12 MS. ZETTLER: Yes. 13 (Deposition Exhibit 10 was marked for 14 identification and a discussion was held 15 off the record.) 16 Q Have you had a chance to review Exhibit 10, 17 Catherine? 18 A Yes. 19 Q Do you recognize the first page of Exhibit 10? 20 A Yes. 21 Q Is this the work sheet that you were talking 22 about a few minutes ago? 23 A No. 24 Q What is this document, this piece of paper, the Page 19 1 first page? 2 A I recall that this was perhaps an early draft 3 of what information we would want to be looking 4 for. 5 Q Would this be information that was included on 6 the ultimate work sheet that was produced? 7 A Yes. 8 Q How long were the work sheets, the forms 9 themselves? 10 A I don't remember the length. 11 Q Was it more than one page? 12 A Yes. 13 Q Was it more than five pages? 14 A Yes. 15 Q Was it more than ten pages? 16 A Probably. 17 Q How was it set up? Was it set up similar to 18 this? 19 A No. 20 Q Describe for me generally how it was set up. 21 A Very similar to a case report form page. 22 Q Why is it that you and your co-workers were 23 sent over to Europe to do this project and the 24 case report forms or copies of the case report Page 20 1 forms weren't simply just sent to Indianapolis 2 instead, if you know? 3 A One was language. 4 Q Any other reasons? 5 A Two would be the need to standardize in order 6 to facilitate data entry. 7 Q Anything else? 8 A No. 9 Q When you say language, you mean for instance 10 the French CRFs may be in French? 11 A Yes. 12 Q And did you and your co-workers -- do you and 13 your co-workers read and speak French, the ones 14 who went to the French affiliate? 15 A I don't know. 16 Q You were at the French affiliate working on the 17 French affiliate, weren't you? 18 A No. 19 Q I believe you said it was UK; you were in the 20 UK; right? 21 A Yes. 22 Q And Italy? 23 A Yes. 24 Q And Germany, is it Germany? Page 21 1 A No. 2 Q Where else? 3 A Spain. 4 Q Spain, okay, I'm sorry. Do you speak Spanish? 5 A No. 6 Q Do you speak Italian? 7 A No. 8 Q How would you be able to read the forms to 9 collect the data then? 10 A I did not read the forms and collect data. 11 Q Who did? 12 A The Spanish or Italian CRAs. 13 Q So what was your job? 14 MR. MYERS: Generally or when she 15 went to these non-English speaking places? 16 MS. ZETTLER: When she was in 17 Europe on the O.U.S. data collection project. 18 A When I was in Italy and in Spain, I helped 19 facilitate and organize the two offices and 20 give instructions on how to complete and fill 21 out general information that would -- that was 22 not -- that was language independent such as 23 the title of the study, the patient number. If 24 there were heights or weights or blood Page 22 1 pressures or number-type items written that I 2 could understand, I helped. 3 Q You helped fill out the work sheets on those 4 items? 5 A Yes. 6 Q When you said you helped facilitate, what did 7 you do to help facilitate? 8 A Every day we had to divide the NCR paper -- it 9 was two parts -- and ship one back to the 10 United States, also do a quality check to 11 assure everything that was in the boxes being 12 shipped back was in there. 13 Q When you say "in there" you mean in the box, 14 actually in the box? 15 A Yes. 16 Q So you just made sure that all the 17 work sheet -- strike that. The work sheet 18 forms were in two parts, I take it? 19 A Yes. 20 Q And you sent one part back to Indianapolis and 21 you kept one part or left one part with the 22 affiliate? 23 A Yes. 24 Q So part of your job was to make sure that the Page 23 1 copies of the work sheets that were to be sent 2 back to Indianapolis were in fact all in the 3 boxes and shipped properly? 4 A Yes. 5 Q How about organization, what did you do to help 6 organize? 7 A Count the number of patients, make sure every 8 visit was copied. If we needed a copy of their 9 actual case report form, I went to the copy 10 machines and copied the copies to be included. 11 Q Were you charged with making any decisions as 12 far as how things would be handled or 13 information would be memorialized on the work 14 sheets, things of that nature? 15 A No. 16 Q Who made those decisions? 17 A Please give me an example. 18 Q Sure. For instance, if somebody from the 19 affiliate was to put down the adverse event 20 term overdose and you were aware that it was a 21 suicide attempt without a drug, for instance, 22 did you have the authority to tell them "I want 23 that recorded as a suicide attempt as opposed 24 to an overdose"? Page 24 1 A No. We had standard ground rules that we were 2 to follow and if there was ever a doubt, we 3 were to not make a decision and just ship it to 4 the United States. 5 Q How would you communicate your doubt to the 6 United States? 7 A We could put stickies on the forms themselves 8 and say that we needed a question when we 9 returned or when this was opened. 10 Q Do you recall that ever happening? 11 A No. 12 Q Did you have the authority to call Indianapolis 13 and talk to anybody to get some guidance on how 14 to resolve a substantive issue such as an 15 adverse event term? 16 A No. 17 Q Were you charged with calling and checking in 18 in Indianapolis at any time during the month 19 that you were in Europe? 20 A I did call frequently. 21 Q What were the purpose of your calls? 22 A Discuss how the project was going, if I was not 23 getting cooperation from affiliates or if it 24 was going to take longer than anticipated. Page 25 1 Q When you say not getting cooperation from 2 affiliates, what do you mean? 3 A If I needed them to -- I'm not their 4 management. If I needed them to work longer 5 hours or on weekends in order to get the 6 project done in a timely fashion. 7 Q So you would call Indianapolis and then 8 somebody from Indianapolis would contact 9 management at the affiliate and light a fire 10 under them, so to speak? 11 A Yes. 12 MR. MYERS: Those are her words 13 (indicating). 14 Q Ask them to stay late? 15 A Yes. 16 Q Why was it that the project needed to be done 17 so quickly? 18 A I don't know the exact details. 19 Q Do you have a general idea? 20 A It was a priority scientifically to find out 21 anything we could about suicidality. 22 Q Whose priority? 23 A Perhaps a corporate priority. 24 Q To your knowledge was the incidence of Page 26 1 suicidality and the use of Fluoxetine ever a 2 priority prior to 1990 at Eli Lilly? 3 A I don't know. 4 Q Last time we talked about hit sheets, the hit 5 review sheets. Do you remember that? 6 A Yes. 7 Q Were those filled out during this project when 8 you were over in Europe? 9 A Yes. 10 Q Were they a part of the work sheets themselves 11 or were they something that was separate? 12 A Can we step back and you ask me or show me one 13 because we might be describing two different 14 things? 15 Q Sure. 16 MS. ZETTLER: Was there one that 17 was connected last time? I can't remember. If 18 not, I've got one I could mark. 19 MR. MYERS: These are the exhibits 20 from the last time (indicating). 21 THE WITNESS: Go back. 22 MR. MYERS: This one. 23 A Exhibit 2 was filled out at the sites. 24 Q That's the cover sheet, the O.U.S. patient Page 27 1 cover sheet; correct? 2 A Yes. 3 MS. ZETTLER: Why don't we mark 4 this as 11. 5 (Deposition Exhibit 11 was marked for 6 identification.) 7 Q Have you had a chance to review Exhibit 11? 8 A Yes. 9 Q Do you recognize this exhibit or the pages 10 comprising the exhibit? 11 A Yes. 12 Q On the top of the first page of Exhibit 11 it 13 says hit review sheet; correct? 14 A Yes. 15 Q Was this the sheet that was filled out while 16 you were in Europe at the sites related to the 17 O.U.S. data collection project? 18 A No. 19 Q Earlier you pointed to Exhibit 2 from last 20 time? 21 A Yes. 22 Q Is that what you considered the hit sheet? 23 A No, that's an O.U.S. cover sheet. 24 Q What form did you use or in what manner did you Page 28 1 record the hits when you were over there? 2 A If there was an act or ideation on the O.U.S. 3 patient cover sheet, act or ideation would be 4 circled yes and some note or our thoughts as to 5 why we think we need to copy the case report 6 form and send it in addition to the work sheet 7 back to the United States; that was considered 8 a (quote) hit. 9 Q And I think last time you said you might have 10 come up with the term hit? 11 A Yes. 12 Q In other words, that sounds like something you 13 would have done? 14 MR. MYERS: She invented it. 15 MS. ZETTLER: Yes. 16 Q Was the O.U.S. cover sheets, Exhibit 2, were 17 they filled out for every work sheet or just 18 the work sheets that you felt were related to 19 suicidal ideation and suicide attempt? 20 A All patients collected had a cover sheet. 21 Q Was that done for each individual visit or just 22 for each patient? 23 A Each patient. 24 Q So attached to that cover sheet would be the Page 29 1 work sheets for each individual visit? 2 A Yes. 3 Q Did you fill out demographic data, history 4 data, previous illnesses, things like that for 5 every single visit or just once for each 6 patient and then record the things that 7 occurred in each visit after that? 8 A Could you repeat that question? 9 Q Sure. I'm just trying to get an idea. I've 10 never seen a work sheet, okay, so I don't know 11 what they look like. I'm just trying to get an 12 idea, you know, of how they were made up. Was 13 it a matter of some information such as the 14 history and the demographic data, things of 15 that nature being recorded once and then -- 16 A Yes. 17 Q Okay. And then after that individual 18 information on each visit, say if it's a change 19 in the HAM-D or something, would be recorded 20 for each visit? 21 A Yes. 22 Q You wouldn't rerecord the person's age and name 23 and location and things of that nature for 24 every single visit? Page 30 1 A You probably would repeat the initials. 2 Q But other than that, the other demographic data 3 like sex, age, birthdate, all of that other 4 stuff you would not repeat for each visit? 5 A It was not repeated. 6 Q So where did the hit review sheet that makes up 7 the first page of Exhibit 11, where did that 8 type of sheet come into the picture? 9 A When the case report -- excuse me. When the 10 work sheets were sent back to Indianapolis, one 11 of these were placed on top if they had an 12 accompanying (quote) case report form or they 13 were considered a hit. 14 Q Were these hit review sheets used for the U.S. 15 data as well as the O.U.S. data or is this 16 something that was used strictly with the 17 O.U.S. data? 18 A O.U.S. data. 19 Q Okay. Were you involved at all in the review 20 of suicidality-related or violent 21 aggressive-related adverse events that were 22 taken from the U.S. database? 23 A I had worked on some of those studies. 24 Q But I mean as far as the actual analysis of, Page 31 1 you know, the retrospective analysis of the 2 data, were you involved in that project at all? 3 A Not to my knowledge. 4 Q When you say not to your knowledge, what do you 5 mean? 6 A As part of my daily job, I don't remember 7 specifically having someone come to me and tell 8 me "You are now working on the U.S. review." I 9 mean I may have in part of my working on the 10 whole team been asked to do tasks during the 11 course of my normal assignments to review 12 things or look at things, but I don't remember 13 ever having a dedicated assignment towards 14 that. 15 Q Were you ever asked to review suicidality 16 adverse events related to U.S. clinical trials? 17 A Yes, I read case report forms that were not 18 included in the database. 19 Q That were not included in the database? What 20 database? 21 A Or not being able to be read in the database. 22 Q Why weren't they able to be read in the 23 database? 24 A It was an older system and some things needed Page 32 1 to be read manually. 2 Q This was a matter of reviewing just 3 suicidality-related clinical report forms or 4 was it reviewing clinical report forms to see 5 if there were any suicidality-related adverse 6 events listed? 7 A I don't remember the specifics of the review. 8 Q When was that done? Was that done before or 9 after the O.U.S. database collection project? 10 A Before. 11 Q Was that done in conjunction with the analysis 12 of U.S. double-blind controlled studies that we 13 talked about earlier? 14 A It may have been. 15 Q Did anybody else work on reviewing those CRFs 16 with you? 17 A I remember all the CRAs that were working on 18 Prozac having some sort of involvement. 19 THE WITNESS: I need a break. 20 MS. ZETTLER: Oh, sure. 21 (A brief recess was taken.) 22 Q Let's go back to the O.U.S. data collection 23 project for a second. How did you know what 24 constituted a suicidality-related adverse Page 33 1 event? 2 A We had a -- I'm trying to decide what to call 3 all this. It's not a rule, but we had some 4 instructions as to if there were anything 5 related or any comments related to harming 6 oneself that we were to copy it and not 7 question. We were to think like a computer and 8 not question it, just copy it. 9 Q You're not a trained psychiatrist or 10 psychologist, are you? 11 A No. 12 Q Were any of the people that went over there, 13 over to Europe with you, the list you gave me 14 earlier, were any of them trained 15 psychiatrists? 16 A No. 17 Q How about psychologists? 18 A No. 19 Q Social workers? 20 A No. 21 Q Therapists? 22 A No. 23 Q Counselors? 24 A No. Page 34 1 Q Did these instructions or guidelines that they 2 gave you to follow, did they give you examples 3 of what types of things would constitute 4 somebody wanting to harm themselves? 5 A Yes. 6 Q Was this in a manual form, these instructions? 7 A No. 8 Q Was it a couple sheets of paper? 9 A Yes. 10 Q Was everybody from Indianapolis who went over 11 to Europe to work on this project, were they 12 all given a copy of these instructions? 13 A Yes. 14 Q Were the affiliates given a copy of these 15 instructions, also? 16 A Yes. 17 Q Give me some of the examples that they gave you 18 as to what type of language or what type of 19 notations would constitute wanting to harm, 20 somebody wanting to harm themselves; in other 21 words, what examples did they give you as to 22 what would indicate somebody wanting to harm 23 themselves? 24 A We were not looking specifically to harming Page 35 1 oneself. We were just told if we saw the words 2 death, kill, self, accident, overdose, suicide, 3 so as if we were like a computer just searching 4 for words. 5 Q So these were words that were -- that you 6 could, if you know, theoretically go through 7 like a clinical trial database and make up a 8 query with these types of words and get 9 information on like the report forms that were 10 stored in the database? 11 A Yes. 12 Q Can you give me any other examples of words 13 that were included on the list? 14 A Hanging, jumping. 15 Q Anything else? 16 A Cutting, drowning. 17 Q Anything else? 18 A Any type of weapon. 19 Q Anything else? 20 A I don't remember anything else. 21 Q How about hopeless, hopelessness? 22 A I don't remember if that was on the list. 23 Q Were you told to look at the Hamilton 24 Depression 3, the HAM-D 3 questions or the Page 36 1 MADRS equivalent? 2 A We had to copy both of those. 3 Q But as far as looking at suicidality? 4 A Yes. 5 Q What guidelines were you given on looking at 6 the HAM-D or the MADRS ratings for suicidality? 7 A If the suicide question on the Hamilton or the 8 MADRS scale was positive, then we were to copy 9 the case report form and consider it a hit. 10 Q When you say positive, what do you mean? 11 A I don't remember the specific question or what 12 the benchmarks for each question were, but if 13 it indicated that they were having some sort of 14 suicidal ideation or act that we were to copy 15 that. 16 Q Let's go back to the list of words that you 17 said they gave you that they felt were related 18 to suicidality. You said earlier I believe 19 that you weren't looking at it just from a 20 suicide point of view. Did you mean that you 21 were also looking for like a violent aggressive 22 or injury to other types of point of view, 23 also? 24 A Any type of injury. Page 37 1 Q Were you told specifically to collect data or 2 flag data on patients who were hostile or 3 violent aggressive towards others? 4 A I don't remember. 5 Q Is hostility one of the words on the list? 6 A I don't remember. 7 Q How about depression, was that one of the words 8 on the list? 9 A I don't believe so since all of these patients 10 should have been depressed in order to be in 11 the trials. 12 Q Are you aware of that at some point in time at 13 least on the COSTART dictionary suicidal 14 ideation map to depression? 15 A Yes. 16 Q As far as adverse events were concerned, were 17 you told to look for adverse events that were 18 termed as depression? 19 A If they indicated that they were in the 20 descriptive term something to harm themselves. 21 Q So in addition to the event term itself, you 22 would look at the narrative? 23 A Yes. 24 Q How about depersonalization? Page 38 1 A I don't recall. 2 Q You don't recall whether or not they asked you 3 to look for that or you don't recall that ever 4 being -- 5 A I don't recall specifically that term, having 6 to look for that term. 7 Q Last time you testified that you took a 8 half-day seminar in adverse events reporting. 9 Do you remember that? 10 A Yes. 11 Q Was that in connection with this project, the 12 O.U.S. database project? 13 A No. 14 Q When did you take that? 15 A At an APA meeting. 16 Q And I think you testified last time that Lilly 17 had asked you to take that class. 18 A No, I don't think they asked me to take it. 19 Q Is it something that you were interested in on 20 your own? 21 A If we go to a seminar such as the APA, 22 sometimes we're allowed to take an additional 23 class that's offered. 24 Q You had prior experience with coding adverse Page 39 1 events and collecting adverse events prior to 2 taking that course though, didn't you? 3 A Yes. 4 Q Why is it that you wanted to take that course? 5 A To expand my knowledge. 6 Q In what way? 7 A It was a continuing education session. I 8 thought perhaps there could be more information 9 to be learned. 10 Q Did you learn anything new from that seminar 11 that you didn't already know? 12 A Not that I remember. 13 Q Tell me what kinds of things they talked about 14 at the seminar. 15 A The seminar was targeted for physician groups 16 and it was mainly a discussion type of 17 different adverse events that are related to 18 particular classes of drugs. 19 Q Did they talk specifically about 20 antidepressants? 21 A Yes. 22 Q Can you tell me what kinds of adverse events 23 they related to the antidepressants? 24 A They were talking -- it was so long ago. Page 40 1 Q To the best of your memory. 2 A For example, that tricyclics may produce 3 anticholinergic side effects. 4 Q Was this seminar on adverse events as they 5 occur or adverse event collecting and 6 reporting? 7 A Adverse events. 8 Q As they occur? 9 A As they occur. 10 Q Did they talk about specifically serotonin 11 reuptake inhibitors, that class of 12 antidepressants? 13 A I don't remember. 14 Q When you reviewed the CRFs from the U.S. 15 trials, you said you reviewed the ones that 16 couldn't be looked at on the computer that were 17 not entered on the computer database. 18 A Yes. 19 Q Did you use the same guidelines or instructions 20 that you used in the O.U.S. data collection 21 project to determine whether or not -- or at 22 least to make a preliminary determination as to 23 whether or not an adverse event was related to 24 suicide? Page 41 1 MR. MYERS: Before she answers, let 2 me just object to the form. I think you 3 misspoke. She said that the U.S. case report 4 forms that she reviewed were in the database. 5 There were just certain aspects which were not 6 susceptible to electronic searching. 7 MS. ZETTLER: I really don't think 8 she said that, Larry. 9 MR. MYERS: I think she did. 10 MS. ZETTLER: Well, then let's 11 clarify that. 12 Q What did you mean when you said they couldn't 13 be reviewed on the computer? 14 A In what Mr. Myers said that I think my 15 interpretation is that they could not be 16 searched by the computer. That database didn't 17 have the ability, a search mechanism, because 18 it was an older database. 19 Q And when you say a search mechanism, you mean 20 search for specific adverse events? 21 A Yes. 22 Q In other words, you couldn't do a computer data 23 search for suicide-related adverse events? 24 A Yes. Page 42 1 Q Yes, you could or, yes, I'm right in what I 2 said? 3 A Yes, you're right in what you said. 4 Q Okay. So when you did this review, did you 5 review the CRFs on the computer or did you 6 review the hard copies? 7 A I believe I reviewed hard copy. 8 Q Is there a certain time cutoff after which you 9 could review or do a search on the computer; in 10 other words, did you have to review all studies 11 that were done prior to -- just as an example -- 12 January 1st, 1989? 13 A I believe there was a cutoff. 14 Q Do you remember what this cutoff was? 15 A No, I do not. 16 Q Do you remember what year it was? 17 A Very early '80s. 18 Q And when you say you reviewed CRFs, did you 19 review CRFs just from double-blind controlled 20 studies or did you review CRFs from all studies 21 that were conducted in the United States prior 22 to that cutoff date? 23 A I don't remember what we reviewed. 24 Q Do you remember reviewing any of the early Page 43 1 toxicology studies in normal healthy patients? 2 MR. MYERS: Well, I'll object to 3 the form. I don't think they're called 4 toxicology studies. 5 Q Do you know what studies that were done early 6 on on healthy non-depressed patients, like 7 Phase -- I believe -- II Studies? 8 A I don't believe that we reviewed those. 9 Q Do you know what I'm talking about when I says 10 Phase II or a -- 11 A Yes. 12 Q Okay. Let's go back to my original question 13 after the break. When you reviewed those CRFs 14 from the studies that were performed prior to 15 the ability to search the data on the computer, 16 were you given guidelines like the ones that 17 you were given when you did the O.U.S. data 18 collection project? 19 A Yes. 20 Q Is that the same form that you used or the same 21 instructions that you used in the O.U.S. data 22 collection project or was it different 23 instructions? 24 A Clarify. Page 44 1 Q In other words, was it essentially the same 2 thing: Look for information that talks about 3 death, kill, self, accident, overdose, 4 et cetera? 5 A It was essentially the same information. 6 Q Do you remember if there were any terms for 7 lack of a better phrase that were included in 8 the O.U.S. instructions that were not used in 9 the U.S. review instructions? 10 A I don't believe so. 11 Q Were you specifically reviewing the CRFs for 12 suicidality-related adverse events, the U.S. 13 CRFs? 14 A I was not so much involved that I remember 15 exactly why we were reviewing them. 16 Q But you do remember that you were looking for 17 suicidality adverse events? 18 A Yes. 19 Q How about hostility or violent aggressive 20 behavior adverse events? 21 A I don't remember. 22 Q What were you told to do with the CRFs that you 23 felt showed a suicidality-related adverse 24 event? Page 45 1 A My recollection is that we were told to put 2 them in a pile. 3 Q And what did you do with the ones that you did 4 not feel were suicidality-related? 5 A They went back in the files. 6 Q What did you do with the pile of CRFs that you 7 felt were suicidality-related? 8 A I believe a physician reviewed them. 9 Q Similar to the hits that were reviewed as a 10 result of the O.U.S. data collection project? 11 A Yes. 12 Q After the U.S. hits -- for lack of a better 13 phrase -- is that okay? Can we use that? 14 A Yes. 15 Q After the U.S. hits were reviewed by the 16 physicians, what happened to them? 17 A I don't remember. I was not that much involved 18 in that project. 19 Q Do you recall a situation where somebody came 20 to you and said, "Out of these hits that you've 21 collected, these should go back into the files 22 because they are not related to suicide"? 23 A I don't remember. 24 Q Did you have responsibility for putting the Page 46 1 documents back in the files after the review 2 was completed? 3 A No. 4 Q Do you know who had that responsibility? 5 A No. 6 Q Let's go back to the O.U.S. data collection 7 project and the hits that resulted from that. 8 What was your responsibility with regard to the 9 review of the hits once they were brought back 10 to Indianapolis? 11 A For the hits I was to have the physicians 12 review them and designate them as either being 13 an act or ideation or that it fell outside the 14 guidelines that were established and that they 15 were to be filed with the rest of the project 16 with the cover sheets. 17 Q You mean you were to designate whether it was 18 an act or ideation or fell outside the 19 guidelines? 20 A No, the physicians were. 21 Q You were just charged with having them do that 22 task? 23 A Yes. 24 Q When you said they fell outside the guidelines, Page 47 1 what do you mean by guidelines? 2 A The physicians had designated guidelines to 3 follow as to the time of any acts or ideations. 4 Q As to the time of the acts or ideations? 5 A For example, if the act or ideation occurred 6 while the patient was on a drug or during a 7 placebo phase or way after the study had ended. 8 Q Any other guidelines that were -- strike that. 9 And depending on where the patient fell within 10 these guidelines, that would at least in part 11 determine whether or not it was considered a 12 related suicidal act or ideation? 13 MR. MYERS: I'll object to the 14 form. Related to what? 15 MS. ZETTLER: To the use of the 16 drug Fluoxetine. 17 MR. MYERS: I don't think she 18 testified that they made that judgment. 19 MS. ZETTLER: That's what I'm 20 asking her, Larry. 21 A Can you ask the question again? 22 Q Sure. When you say guidelines -- and then part 23 of the guidelines at least were the time of 24 when the act or ideation occurred; correct? Page 48 1 A Yes. 2 Q And if the act or ideation occurred, say, 3 during the placebo phase of a trial, then it 4 makes sense that it wouldn't be related to the 5 Fluoxetine or the other study drug that the 6 person was put on; correct? 7 A There was no causality base; it was just 8 determined that it didn't occur during an 9 active drug phase. 10 Q You also testified a little bit earlier that if 11 it fell outside the guidelines, if the act or 12 ideation fell outside the guidelines, it would 13 be placed back with the other information that 14 wasn't being considered suicidality-related; 15 right? 16 A Yes. 17 Q How did the time -- if they're not talking 18 about a causality question here, how does the 19 time of when it happened, the act or ideation 20 happened, relate to whether it was related to 21 suicide? 22 MR. MYERS: Well, before she 23 answers, let me object only to the extent that 24 may call upon her to give some sort of a Page 49 1 medical opinion. 2 MS. ZETTLER: To the extent she 3 knows. 4 MR. MYERS: All she's doing is 5 recounting to you I think what the physicians 6 did. 7 MS. ZETTLER: Okay. That's fine. 8 A I was given back two -- essentially two piles 9 to organize, one for further review and one to 10 refile. 11 Q Were there any other guidelines that were taken 12 into consideration in determination of whether 13 or not adverse events should be refiled or 14 reviewed further besides the time of when the 15 act or ideation occurred? 16 A I don't remember what the medical -- what the 17 physicians' criteria -- specific medical 18 criteria may have been. 19 Q So besides the time of the occurrence of the 20 act or ideation, there were other factors that 21 were taken into consideration on the review by 22 the physicians at this point in the process? 23 A There may have been. 24 Q But the one that sticks out in your head the Page 50 1 most is the time when the act or ideation 2 occurs? 3 A Yes. 4 Q Were these written guidelines to your 5 knowledge? 6 A No, not to my knowledge. 7 Q To your knowledge was the same done with hits 8 related to injury to others or hostility? 9 A I don't know that answer. I don't remember. 10 Q And the pile of CRFs that you were given back 11 or the hits that you were given back to refile 12 simply were put back with the rest of the CRFs; 13 correct? 14 A Works sheets. 15 Q Work sheets. Okay, I'm sorry. That's right. 16 We're back on O.U.S. Did you feel comfortable 17 in making an initial determination as to 18 whether or not an adverse event was related to 19 suicidality? 20 A Yes. 21 Q Why? 22 A Because I had been a CRA in this group for long 23 enough and I knew I wasn't making an absolute 24 decision. If there was any question in my mind Page 51 1 or any word, I was thinking just as I said 2 earlier like a computer and just passing on the 3 information. 4 Q Did you look at the pile of work sheets that 5 you were given to refile when they were given 6 back to you? 7 A Only to determine if both physicians had 8 reviewed them and I think I kept a spreadsheet 9 logging them in and out so we could keep track 10 of them. 11 Q How is that spreadsheet set up? 12 A I don't remember. 13 Q Did it include the PIP numbers: Patient, 14 Investigator, Project numbers? 15 A Yes. 16 Q Did it include the names of the physicians who 17 reviewed the hits? 18 A I remember it had the initials. 19 Q Do you know if these hits were ever submitted 20 to outside consultants for review? 21 A Not that I'm aware of. 22 Q Are you aware of outside consultants ever being 23 asked to review specific cases of suicidal 24 ideation or suicide attempt? Page 52 1 MR. MYERS: As far as this project 2 or any project? 3 MS. ZETTLER: Well, let's just go 4 with this project. 5 MR. MYERS: Are you talking about 6 O.U.S.? 7 MS. ZETTLER: Yes. Let's start 8 with the O.U.S. 9 A Not that I recall. 10 Q Were there physicians at the sites that 11 reviewed the CRFs and the work sheets to decide 12 whether or not they were related to suicidality 13 and -- 14 MR. MYERS: When you say the sites, 15 you mean the affiliates? 16 MS. ZETTLER: The affiliates, I'm 17 sorry. 18 MR. MYERS: That did the same task 19 that she was just talking about that she and 20 the others did? 21 MS. ZETTLER: Right. 22 A There were physicians that were there, but I 23 don't -- I don't know what kind of role they 24 played. Page 53 1 Q But it wasn't a matter of you thinking, well, 2 Patient Number 12 looks like they suffered from 3 a suicide attempt and you had to go and get an 4 okay from a physician there in, say, Spain? 5 A No. 6 Q Other than looking at the CRFs that you were 7 told to -- or I'm sorry, strike that. Other 8 than looking at the work sheets that you were 9 told to refile with the rest of the work sheets 10 after the physicians reviewed them to log them, 11 did you rereview them as far as the content? 12 A Not unless they had a specific question. 13 Q Did you ever take exception with the refiling 14 of a work sheet related to anything that you 15 thought was suicidality-related; in other 16 words, did you ever look at a work sheet that 17 you were to refile and say "I really think that 18 this is related to suicide and Dr. So-and-So 19 doesn't"? 20 A I don't remember any specific incidents. 21 Q Do you remember generally feeling that way? 22 A No. 23 Q Did anybody at Lilly ever tell you that they 24 felt that the determinations being made by the Page 54 1 doctors were either too broad or too narrow 2 with regards to suicidality on the hits? 3 A Not that I remember. 4 Q Did you ever meet Claude Bouchy? 5 A No. 6 Q Have you ever talked to him on the phone? 7 A Not that I remember. 8 Q Do you know who he is? 9 A No. 10 Q With regards to the review of the pre-early '80 11 U.S. clinical report forms, ones that you 12 couldn't search on the computer, do you recall 13 in how many instances you pulled CRFs related 14 to suicidality? 15 A No, I don't remember. 16 Q Do you know if it was more than ten? 17 A I don't remember at all. 18 Q How about the O.U.S. hits, do you recall how 19 many hits you pulled? 20 A Hundreds. 21 Q Hundreds? When you say hundreds, do you mean 22 more than five hundred? 23 A I really don't remember. 24 Q But more than a hundred obviously? Page 55 1 A Yes. 2 Q Could it be more than a thousand? 3 A No. 4 Q Would this log that you kept, would that 5 reflect every hit that was pulled from the 6 O.U.S. data? 7 A It should have. 8 Q Were any of your other co-workers that went 9 over to Europe with you on that project, were 10 they charged with keeping a log, also? 11 A No. 12 Q You were the CRA that was in charge of 13 organizing, distributing, collecting, filing, 14 logging hits; correct? 15 A I was the CRA that was responsible for the 16 O.U.S. project when I returned to the United 17 States, so I logged all cases. 18 Q How many doctors at Lilly Indianapolis reviewed 19 the hits? 20 A Two. 21 Q I think you testified last time it was 22 Dr. Beasley and Dr. Wheadon or am I getting 23 confused again? 24 A No, I don't believe Dr. Wheadon was involved. Page 56 1 MR. MYERS: O.U.S. now; right? 2 MS. ZETTLER: Right, O.U.S. 3 Q Heiligenstein? 4 A Yes. 5 Q Sorry about that. It's hard to keep everybody 6 straight after a while. And I believe you 7 testified last time that each of the doctors 8 independent of each other reviewed the same 9 hits; correct? 10 A Yes. 11 Q Okay. Were the hits that you were given back 12 to file the hits that both Dr. Beasley and 13 Dr. Heiligenstein felt were not 14 suicidality-related? 15 A Yes. 16 Q In other words, if Dr. Beasley felt it was 17 suicidality-related but Dr. Heiligenstein 18 didn't, it would be reviewed further? 19 A Yes. 20 Q What happened on that further review? What was 21 the next step in the process as far as 22 reviewing the suicidality-related hits? 23 A That they did not agree on? 24 Q Sure, we could start with that. Page 57 1 A They were just supposed to discuss between 2 themselves or ask somebody else, probably one 3 of the other physicians, to come to terms on 4 why they fell out of range or they didn't 5 concern each other. I think there were only 6 very few cases. 7 Q And then after all of the disagreements about 8 those hits were resolved, what happened with 9 the hits then; in other words, say they were 10 all decided that they were suicidality-related, 11 what happened with that group of hits that was 12 decided were suicidality-related? 13 A They were filed. 14 Q Where? 15 A They were filed so we would have access to them 16 more often and they were probably in one of the 17 conference rooms. 18 Q Now, when a CRF was pulled as being related to 19 suicide, would you pull the entire CRF for that 20 subject, for that patient; in other words, if 21 they had eight visits, would all the records 22 for every single visit be included? 23 A Yes. 24 Q How much space did the suicidality-related hits Page 58 1 take up? 2 A I think a box. 3 Q One box? 4 A (Affirmative nod). 5 Q And that was the work sheets for those hits; 6 would those be included in that box? 7 A Yes. 8 Q How about originally, how many boxes would the 9 hits that you and your co-workers pulled from 10 the O.U.S. data before they were reviewed by 11 the doctors, how many boxes would they fill? 12 A They weren't ever put in boxes, so they were 13 all lined up on the table. 14 Q In stacks? 15 A Yeah. 16 Q How big were the stacks? 17 A There were so many piecemeal parts of this that 18 not everything was sent in at the same time, so 19 the stacks kept moving. It's hard to 20 determine. There were a lot. 21 Q When you say "piecemeal parts", you mean hits 22 would come in from, say, Spain and then next 23 week they would come in from, say, France, of 24 that nature? Page 59 1 A Yes. 2 Q What percentage of the total number of hits 3 that were originally collected and submitted by 4 you and your co-workers to the doctors were 5 ultimately decided were suicidality-related? 6 A I don't remember the percentage. 7 Q It seems like you testified, you know, that the 8 end result of the suicidality-related work 9 sheets ended up in one box essentially; 10 correct? 11 A Yes. 12 Q But yet there were stacks that were lined up on 13 tables and coming in on a weekly basis and 14 things of that nature? 15 A Yes. 16 Q Can you give me an estimate? Was it 17 10 percent; was it 20 percent? 18 A I would have to make an estimate that it was 10 19 to 20 percent. 20 Q So 10 to 20 percent of the hits that you and 21 your co-workers initially submitted to the 22 clinical research physicians at Lilly in 23 Indianapolis for review related to suicidality 24 were determined by those doctors to be in fact Page 60 1 related to suicidality? 2 A Yes. 3 Q Do you know if a review of data collected from 4 other indication trials such as, say, bulimia 5 was ever collected and analyzed like the data 6 from the double-blind controlled studies from 7 the depression trials? 8 A Not that I'm aware of. 9 Q To your knowledge was the study such as the 10 O.U.S. -- strike that. To your knowledge was 11 the project such as the O.U.S. data collection 12 project ever done specifically to look at the 13 question of hostility or homicidality? 14 A Not that I'm aware of. 15 Q At your jobs prior to working at Lilly I think 16 you stated last time that at least in one job 17 you worked on clinical trials for cardiac 18 drugs? 19 A Yes. 20 Q Was that a Lilly drug or were any of those 21 Lilly drugs? 22 A Yes. 23 Q In your previous employment prior to Lilly, did 24 you ever work with a clinical investigator that Page 61 1 ended up working on a Fluoxetine clinical trial 2 to your knowledge? 3 A No. 4 Q This adverse event seminar that you took 5 through the APA, were there any other Lilly 6 employees at that seminar? 7 A Yes. 8 Q Can you give me some of their names? 9 A Ray Albritton. 10 Q I'm sorry, Ray? 11 A Yes. 12 Q Who is Ray Albritton? 13 A He was a CRA. 14 Q Was he working on Fluoxetine? 15 A I believe he was. 16 Q Did he work on either the review of the CRFs 17 from the U.S. trials or the O.U.S. data 18 collection projects? 19 A I don't know about the U.S. project and I don't 20 believe he worked on the O.U.S. project. 21 Q If we could look back at Exhibit 11, on the 22 left-hand margin of the page it's got a number 23 of titles. 24 MR. MYERS: Which page? Page 62 1 MS. ZETTLER: I'm sorry, the first 2 page. 3 Q I don't want to know about any details written 4 on here. Right now I'm just interested in the 5 different parts of the form itself, okay? 6 Obviously the first one says facility. Would 7 that be the affiliate or the site? 8 A Affiliate. 9 Q On the project number as it says underneath 10 that, would that be the individual clinical 11 trial or would that be the process of actually 12 going through all the clinical trials and 13 collecting the data; in other words, did the 14 O.U.S. database project have a project number 15 of its own? 16 A No. 17 Q A couple of lines down from there it says 18 reason or reasons for hits. 19 A Yes. 20 Q Who was to fill that out? Is that something 21 that, say, you were to fill out? 22 A Yes. 23 Q And that information underneath, HAM-D and 24 visits; MADRS/visits; ADE page/visits; things Page 63 1 of that nature, were you to fill out all that 2 information, also? 3 A Yes. 4 Q As well as the comment? See the comment 5 portion at the bottom of that group? 6 A Yes. 7 Q What information was the psychiatrist or the 8 doctor at Lilly supposed to fill in on this 9 form if any? 10 A The comments from the psychiatrist, act, 11 ideation, not a case, and their signature and 12 date. 13 Q On the first page of Exhibit 11 it says under 14 "not a case", died by hanging, apparently 15 taking drug in compliance. Is that in this 16 case Dr. Beasley's or would that be 17 Dr. Beasley's handwriting; in other words, 18 would the psychiatrist fill that part in or 19 would that be something that you would fill 20 out? 21 A No, the physician filled that in. 22 Q And then underneath that where it says per 23 1639, date of death is 9-3-85, is that your 24 handwriting? Page 64 1 A Yes. 2 Q Is that your signature underneath that? 3 A Yes. 4 Q Was this information something that you 5 typically put on these forms for the physicians 6 or was this something that was done in response 7 to a question? 8 A That was probably in response to a question. 9 Q Towards the middle of the page it says DEN, 10 yes, and then MC number. Is that manufacturer 11 control number? 12 A Yes. 13 Q And where it says date, what's that date 14 reflective of, the date that it was put into 15 DEN? 16 A DEN date. 17 Q Manufacturer control number -- it's kind of 18 hard to read on this copy -- but generally is 19 that the control number that's put on the 1639 20 if one is filled out? 21 A Yes. 22 Q Is this also the DEN number to your knowledge? 23 A I've never heard of DEN number. 24 Q In other words, if I were going to fill out a Page 65 1 1639, say on a suicide, okay, and a 2 manufacturer control number was assigned, would 3 that be the same number that I could go to the 4 DEN database and pull up information on that 5 patient? 6 A Yes. 7 Q Did you fill out any 1639s as a result of any 8 of the hits that you found in the O.U.S. 9 collection project? 10 A Yes. 11 Q On how many occasions? 12 A Maybe ten. 13 Q And why did you fill those 1639s out on those 14 ten occasions? 15 A According to my understanding of the law, and 16 based on perhaps I think Dr. Beasley's, that we 17 should complete a 1639 because one was not 18 completed. 19 Q So in other words, if a 1639 had never been 20 filled out on this adverse event, then you 21 would complete a 1639 out on it? 22 A Yes. 23 Q What was done with the 1639 when you completed 24 it? Page 66 1 A It was sent to the Drug Epidemiology Unit. 2 Q At Lilly? 3 A Yes. 4 Q And is this regardless of whether or not it was 5 a clinical trial that was performed before or 6 after 1987? 7 A Yes. 8 Q Was it Lilly's policy as far as you know to 9 fill out a 1639 on adverse events that occurred 10 during clinical trials? 11 A I'm sorry, ask that question again. 12 Q Sure. Do you know if it was Lilly's policy or 13 if you were instructed -- well, let me ask it 14 this way: Were you instructed as a CRA that if 15 you became aware of a 1639 that occurred during 16 a clinical trial, you were to fill out a -- 17 MR. MYERS: An adverse event. 18 Q Let me start again. Were you told when you 19 were working as a CRA that if you became aware 20 of an adverse event that occurred during a 21 clinical trial regardless of whether or not it 22 was before 1987 when the drug was approved by 23 the FDA that you were to fill out a 1639? 24 A It's my understanding as a Lilly employee that Page 67 1 at any time I'm aware of an adverse event 2 happening on any Lilly compound I am required 3 to report it. 4 Q Through a 1639? 5 A Yes. I'm familiar with 1639s. I could report 6 it by just calling the Drug Epidemiology Unit. 7 Q But my question goes more to the requirement of 8 actually filling out a 1639. I'm not saying 9 you have to specifically fill it out if you 10 hear of an adverse event, but is it your 11 understanding that Lilly required a 1639 be 12 filled out on any adverse event that they heard 13 about? 14 A Yes. 15 Q Regardless of whether or not it's an adverse 16 event that occurred during a clinical trial? 17 A Yes. 18 THE WITNESS: I need to take a 19 break. 20 MS. ZETTLER: Do you want to just 21 break for lunch? 22 MR. MYERS: Yes, that's fine. 23 (A lunch recess was taken.) Page 68 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 MR. MYERS: Before we go on, Nancy, 5 Ms. Mesner had a clarification to your question 6 about when to report an adverse event on a 1639 7 or otherwise for a clinical trial or 8 post-market. Go ahead and explain. 9 THE WITNESS: Okay. If you're in a 10 clinical trial, you report a 1639 for (quote) 11 serious events. And those are -- there is 12 certain criteria for those serious events. 13 Q Those being like death, hospitalization, 14 overdose, congenital anomaly, cancer, things of 15 that nature set up by the FDA? 16 A Yes. 17 Q But you do fill out a 1639 for those types of 18 events? 19 A Yes. 20 Q To your knowledge are those 1639s then sent to 21 the FDA? 22 A Yes. 23 Q And the same holds true about what we talked 24 about earlier, the manufacturer control numbers Page 69 1 and the DEN number or, you know, the number in 2 the DEN is the same? 3 A Yes. 4 Q And if you wanted to look at a 1639 and track 5 it in the DEN, you'd use that manufacturer 6 control number? 7 A Yes. 8 MR. MYERS: I think her point was 9 she just didn't want you to think that for 10 clinical trials there is always a 1639. 11 MS. ZETTLER: It's understood. 12 MR. MYERS: As I understand, 13 everything gets reported. It's just in a 14 clinical trial some of it is on a 1639 under 15 whatever the regulation is and others is in 16 summary or periodic fashion. And I don't know 17 if the problem was with the question or the 18 answer or both, but you've been told that 19 before. 20 MS. ZETTLER: Yes, I understand. I 21 understand. 22 Q What happens to the non-serious adverse events 23 that occur in a clinical trial as far as 24 reporting it and storing it at Lilly? Page 70 1 A They're on the adverse event pages of the case 2 report forms and those are periodically 3 summarized and reported either through annual 4 reporting mechanisms or final reports to the 5 FDA. 6 Q Final reports meaning final reports on that 7 particular trial? 8 A Yes. 9 Q Are the non-serious clinical trial adverse 10 events stored in the computer database at 11 Lilly? 12 A Yes. 13 Q What database is that? 14 A I don't know if there is a specific name for 15 the databases. 16 Q They're not stored in the DEN? 17 A They're not stored in DEN, no. 18 Q They're stored in some other database whether 19 it's a database for the entire clinical trial 20 or a separate adverse event database for 21 clinical trial non-serious adverse events? 22 A Yes. 23 Q I have a couple more questions about the O.U.S. 24 data collection project before we move on. I Page 71 1 just want to make sure that I understood what 2 you said earlier. I'm probably just confused, 3 okay, but I want to make sure that I understand 4 you. You and your co-workers went over to 5 Europe or other of the outside U.S. affiliates 6 and collected data on all patients in the 7 double-blind controlled depression trials 8 regardless of whether or not they had a 9 suicidality-related adverse event; correct? 10 A Yes. 11 Q With regards to those suicidality and/or 12 hostility-related adverse events I think your 13 testimony is you don't remember if there was a 14 specific call to look specifically for 15 hostility, but it may or may not have happened; 16 right? 17 A Yes. 18 Q Regardless, those that you considered hits were 19 noted on the O.U.S. cover sheets and then set 20 aside back in Indianapolis as hits to be 21 reviewed by Dr. Beasley, Dr. Heiligenstein; 22 correct? 23 A Yes. 24 Q When you said that there were hundreds of hits, Page 72 1 were you talking about that original number 2 that were brought back and transferred to 3 Dr. Beasley and Heiligenstein or were you 4 talking about the number that were left after 5 Dr. Heiligenstein and Dr. Beasley reviewed 6 them? 7 A Hundreds referred to those on the first pass, 8 meaning those that were reviewed in Europe 9 without any judgments being made, just sent 10 back as hits. 11 Q The original hits that were collected by you 12 and your co-workers? 13 A Yes. 14 Q Okay. And then from that number, the hundreds, 15 whatever that number is, it's your estimate 16 that 10 to 20 percent of those hits were 17 determined to be suicidality-related by 18 Dr. Heiligenstein and Dr. Beasley; correct? 19 A Yes. 20 Q I wasn't sure if you meant hundreds before or 21 after. And you logged all of the hits as they 22 came in from you and your co-workers from 23 outside the U.S. and kept track of them on that 24 log throughout the process of the review with Page 73 1 Dr. Beasley and Dr. Heiligenstein; right? 2 A Yes. 3 Q Did you note on this log which of the hits were 4 then put back into the -- for lack of of a 5 better phrase -- non-suicide hits or work sheet 6 piles? 7 A I believe if they were marked and no longer a 8 hit that there was some indication that they 9 had been reviewed and went back to the file. 10 Q So your log should have that information on it? 11 A Yes. 12 MS. ZETTLER: Okay. We're on 12? 13 MR. MYERS: 12. 14 (Deposition Exhibit 12 was marked for 15 identification.) 16 THE WITNESS: Can I see it? 17 MR. MYERS: Sure. Off the record a 18 minute. 19 (A discussion was held off the record.) 20 Q Catherine, have you had a chance to review 21 Exhibit 12? 22 A Yes. 23 Q Are you familiar with this exhibit? Do you 24 recognize it? Page 74 1 A Parts. 2 Q What parts do you recognize? 3 A Everything after the first page. 4 Q Let's talk about the first page for a second 5 though. Earlier you testified that it was your 6 job to make sure the physicians did certain 7 things with the hits once you gave them to 8 them? 9 A Yes. 10 Q On this first page it says "O.U.S. Suicide 11 Analysis Definition, Physicians' Requirements." 12 Are these the requirements that you were 13 talking about earlier that it was your job to 14 make sure the physicians completed with regards 15 to the hits? 16 A These look like those requirements. 17 Q So when you say you don't recognize the first 18 page, you've just never seen it memorialized 19 like this before? 20 A I don't remember seeing it. 21 Q Looking over this it says "Prozac physicians 22 will be responsible for providing the following 23 data for patients which the physicians have 24 classified as an act:" Now, do they mean Page 75 1 suicide act to your knowledge? 2 A To my knowledge, yes. 3 Q And then underneath there, there is criteria. 4 They're supposed to give the facility, project, 5 the investigator and the patient. Those are 6 the numbers, I'm assuming? 7 A Yes. 8 Q The PIP number plus a facility code? 9 A Yes. 10 Q And then the date, when the act occurred at 11 least as far as the visit is concerned? 12 A (Affirmative nod). 13 Q And the date? 14 A Yes. 15 Q And then on Number 6 it says "Explanation. 16 List what parameter". And then it says (HAM-D, 17 MADRS, Adverse Event, Comments, etc.) and its 18 value. Do you know what they mean by that and 19 what this means, what that means? 20 A To me that would mean what parameter indicated 21 that you had some idea that there was an act 22 involved; for example, a Hamilton score or a 23 comment. 24 Q So if in the comments it said or if they made a Page 76 1 comment, for instance, "I want to kill myself", 2 then obviously that would be at least taken 3 into consideration in the analysis? 4 A Yes. 5 Q Is Number 6 what you were talking about earlier 6 when you said if it met the criteria, meaning 7 the hit? 8 A No. 9 Q How does this differ from the criteria then? 10 A I think the criteria would be more defined. 11 Q In other words, like you were talking about 12 earlier, say there is a HAM-D score of 4, 13 HAM-D 3 score of 4 or something like that; in 14 other words, the HAM-D may be part of the 15 criteria, but it would be more specific as to 16 what it was about the HAM-D that they would be 17 looking at? 18 A Yes. 19 Q Okay. You testified that you were familiar 20 with all the pages following or portions of the 21 document following the first page; correct? 22 A Yes. 23 Q Can you tell me what the next pages are up to 24 where we start seeing the actual hit review Page 77 1 sheets. 2 MS. ZETTLER: And just for the 3 record that would be Pages 1462, 1627 through 4 1640. 5 A Each page? 6 Q Well, if you can tell me generally what it is, 7 then we can go from there. 8 A These look like queries. 9 Q Queries to whom or to what? 10 A For example, a query on page -- excuse me, 11 which is the page number? 12 MR. MYERS: Just you can use the 13 last four numbers. 14 MS. ZETTLER: Yes. 15 A 1627. 16 Q Okay. 17 A A query of what MADRS Item 10 scores were a 6. 18 Q You mean for those patients from the O.U.S. 19 data collection project who showed a MADRS 10 20 score of 6? 21 A Yes. 22 Q How do you know that? 23 A Because it identifies this as being the O.U.S. 24 project, and under MADRS Item 10, suicide, my Page 78 1 recollection is that 6 is considered a suicide 2 and therefore it's -- or suicidal and they 3 queried that question to find out how many 4 patients had that question answered 6. 5 Q Okay. There is nothing from the top of the 6 page where it says "Listing Of The MADRS 7 Question Number 10 For All O.U.S. Patients 8 Previously Found Occurrences Only"; that 9 indicates that they were asking specifically 10 for people with MADRS Item 10 scores of 6; 11 right? 12 A It -- I'm sorry. It is included in the title 13 as well. You were just quoting the title; 14 correct? 15 Q Right. But it doesn't say anything about a 16 MADRS Question Number 10 score of 6, does it? 17 A No. I was going back down to the -- 18 Q So it's the fact that on the right side of the 19 page under MADRS Item 10, suicide, all of the 20 patients listed had a score of 6; that makes 21 you assume that that's what they were asking in 22 this query? 23 A Yes. 24 Q It could be that these people that are listed Page 79 1 on this page just happened to have the same 2 score on the MADRS 10; right? 3 A Yes. 4 Q Now, on the title it says "Previously Found 5 Occurrences Only." What does that mean to you? 6 A I don't know. 7 Q Could that be patients whose score of the MADRS 8 Item 10 had already been known or recorded as 9 having registered a 6 on that item? 10 A I don't know what it means at all. 11 Q How about the next page, 1628? 12 A Looks like a query for Hamilton Question 3 and 13 the total. 14 Q And it appears that this query goes for three 15 pages, does it not, 70 patients? 16 A Yes. 17 Q And all of those patients have an Item 3 score 18 on the HAM-D of 4; correct? 19 A Yes. 20 Q Which is the highest score you can have on that 21 HAM-D rating; isn't that true? 22 A I don't remember. 23 Q But your understanding is this means that this 24 person is at least suffering from suicidal Page 80 1 ideation? 2 A It means that their score was probably a 4. 3 Q But I mean do you know as far as the rating 4 scale is concerned if you rate a score on the 5 HAM-D 3, does that indicate that you're 6 suffering suicidal ideation? 7 A I don't remember the benchmark to each point on 8 the questions. 9 Q And at the top here as part of the title it 10 says "Newly Found Occurrences Only." Does that 11 refresh your recollection any as to what they 12 mean by previously found occurrences? 13 A No. 14 Q The next page it says "Licensing Of O.U.S. 15 Patients Reporting The Following Elect Terms: 16 Suicide, overdose, intentional overdose and 17 depression." The list we talked about earlier 18 that you were given to follow when you reviewed 19 the O.U.S. clinical trial data, was that list 20 really a list of adverse event terms? 21 A No. 22 Q No, okay. Were these four terms or four items 23 included on that list? 24 A Maybe. I say that because I'm not certain Page 81 1 about depression. 2 Q On the left-hand side it says "OBS". Do you 3 see that at the top? 4 A Uh-huh. 5 Q What is OBS? 6 A Observation. 7 Q So observation number one could be the same 8 patient as observation number two? 9 MR. MYERS: On this or on a report 10 like this? 11 MS. ZETTLER: On this. 12 A On this, no. 13 Q Let's use the next page as an example. I think 14 that might be a better example. At the top it 15 says "OBS, Facility Code, Project Code, Project 16 Code", then it has 1, 2, 3, 4. Do you see that 17 listed? 18 A Yes. 19 Q And then under facility code it looks like all 20 the same facility; correct? 21 A Yes. 22 Q And the first three at least looks like the 23 same project, doesn't it? 24 A Yes. Page 82 1 Q So as far as we know, these first three could 2 be for the same person; correct? 3 A No. 4 Q Why not? 5 A Because the first two look like they could be 6 from the first patient, but then on visit 7 number you jump down to one. 8 Q I see, okay. The point I'm trying to get at is 9 you could have more than one observation for 10 each patient on this as a result of this query. 11 A Yes. 12 Q And we don't know for sure at least on 13 Page 1632 if the first two are in fact the same 14 person because we can't see the patient number 15 because it's blacked out; correct? 16 A Correct. 17 Q If you could go to the next page, at the top 18 again it says: "Listing Of O.U.S. Patients 19 With An Event Actual Term Containing One Of The 20 Following:" And then it says -- looks like it 21 has abbreviations for suicide, then it has 22 self, intentional, over, asphyxia, gun, 23 hospital, et cetera. Are all of these words 24 included on that list that you were given to Page 83 1 follow when you reviewed the data? 2 A I believe so. 3 Q To your knowledge were any other words besides 4 these included in that list? 5 A Maybe. I don't remember. 6 Q Would seeing that list help you refresh your 7 recollection as to what was on the list and 8 what was not on the list? 9 A Just over time I just don't remember. 10 Q But to your knowledge there was at least at one 11 point in time -- or to your memory there was at 12 least at one point in time an actual list that 13 you were given to follow as far as trying to 14 pick out hits then when you reviewed the O.U.S. 15 data; correct? 16 A Yes. 17 Q Would you have had a copy of that list in your 18 files? 19 A Maybe at one time. 20 Q Do you remember throwing that list away? 21 A No, I don't remember throwing it away. 22 Q Do you remember purging your files of 23 everything related to the O.U.S. data 24 collection project? Page 84 1 A No. 2 Q If it was still in your files, would it have 3 been turned over to the legal department at 4 Lilly? 5 A Yes. 6 Q Is any of the handwriting on any of these pages 7 prior to where the hits start, hit review 8 sheets start, yours? 9 A Yes. 10 Q Which page or pages? 11 A It's hard to say if check marks are mine. 12 Q How about on Page 1628 on the right-hand side? 13 A The N/As? 14 Q Yes. 15 A It could be. 16 Q Do you have recollection of going over this 17 sheet and writing in N/As? Or it looks like 18 there's an act in there, too. 19 A I don't have recollection of that. 20 Q Any of these other pages that you do recognize 21 your handwriting on? 22 A 1636. 23 Q And it's the handwriting on the left-hand side 24 of the page? Page 85 1 A Yes. 2 Q Do you recall marking up this page? 3 A No. 4 Q Can you tell from what is written there what 5 you were doing? 6 A Probably pulling a specific case to check it. 7 Q So where it says "pull", that is your 8 handwriting? 9 A Looks like my handwriting. 10 Q How about the rest of the handwriting on the 11 page, on the left-hand side at the bottom? 12 A It could be. I'm not totally certain. 13 Q Did you make these queries? Did you ask for 14 this information? 15 MR. MYERS: Well, that's maybe two 16 different questions as to whether she asked for 17 it and whether she did it. 18 MS. ZETTLER: You're right. 19 Q Did you make these queries? 20 A No. 21 Q Did you ask for this information? 22 A Yes. 23 Q In conjunction with what? 24 A Based on the date of this query, it looks as Page 86 1 though this was probably a quality check 2 towards the end of the data entry to assure 3 that everything was entered and anything that 4 needed to be pulled was pulled or looked at. 5 Q Why would something need to be pulled? 6 A To look at it. 7 Q By whom? 8 A A physician. 9 Q From what perspective or for what reason? 10 A For example, on 36 there was a death and to 11 assure that that death had been accounted for. 12 Q Accounted for in what way? 13 A That it had been a hit. 14 Q Let me ask you this: When you brought back the 15 information, the work sheets from Europe from 16 the O.U.S. project, what happened to them 17 generally when you got them back to the United 18 States? 19 A Generally they were entered into the computer 20 system. 21 Q Regardless of whether or not they were a hit? 22 A Regardless of whether or not they were a hit. 23 Q When the hits were pulled and the physician 24 reviewed the hits, was that done before or Page 87 1 after the hits were entered into the computer 2 database? 3 A I don't remember. 4 Q Do you remember how long it took to enter all 5 of the O.U.S. work sheet data into the 6 databases? 7 A Months. 8 Q I think you testified earlier that you and your 9 co-workers were over in Europe for a month 10 collecting data; is that true? 11 A Yes. 12 Q How long after you guys returned to the United 13 States did all of the information from the 14 O.U.S. database collection get back to 15 Indianapolis? 16 A Within a few weeks. 17 Q And how long after the data got back to 18 Indianapolis was it entered into the computer? 19 A It took months for everything to be entered in. 20 Q When you say everything, what do you mean? 21 A Every visit for every patient. 22 Q How many months? 23 A My guess would be three or four. 24 Q If you could look at the first few pages of Page 88 1 hits starting with 1641 through, say, 1644. 2 A Okay. 3 Q Generally those signatures, the physician 4 signatures are dated in February, looks like 5 mid to late February of 1991, correct, just 6 from the first few pages? 7 A Yes. 8 Q Does that refresh your recollection as to 9 whether or not the hits were reviewed before 10 they were entered into the computer database? 11 A Based on this, it looks like they were probably 12 reviewed after. 13 Q After they were entered? 14 A Yes. 15 Q When the hits were pulled for review by the 16 physicians, was that done manually or was that 17 done through the computer? 18 A Manually. 19 Q Was your log, the log that you kept on the hits 20 that were reviewed by Drs. Beasley and 21 Heiligenstein, was that double-checked against 22 queries such as the ones on the first few pages 23 of this exhibit to see if you had gotten all of 24 the hits and had them reviewed? Page 89 1 A I believe that's correct. 2 Q Do you remember if there were hits that were 3 missed on the manual review that were picked up 4 by the computer? 5 A I don't believe there were any. 6 Q Including the death that you pointed out on 7 Page 1636? 8 A I don't remember, but I don't remember having 9 to call Europe and having anything else sent 10 either. 11 Q What about that information -- when I say the 12 manual review, I mean once it got back to the 13 United States. I believe it was your testimony 14 earlier that you looked at the stuff as it came 15 in and pulled the stuff that was noted on the 16 O.U.S. and gave it a hit sheet and submitted it 17 to the doctors for review; correct? 18 A Yes. 19 Q Did you ever double-check your own work, the 20 manual pulling of those hits for review for the 21 doctors against the computer queries such as 22 the ones at the beginning of Exhibit 12? 23 A Yes, I believe that's what those queries were 24 for. Page 90 1 Q And from that, from the queries, do you recall 2 whether or not you had missed any? 3 A I don't believe so. 4 (A discussion was held off the record.) 5 Q Let's talk about the rechallenge protocols. I 6 think your testimony last time is that you 7 recalled that there were three prospective -- 8 not prospective -- but possible details related 9 to the studies that you worked on. 10 A Yes. 11 Q One was the actual rechallenge protocol; 12 correct? 13 A Yes. 14 Q The other was a surveillance study to validate 15 the MSSI-R? 16 A Yes. 17 Q And the third one you weren't sure if you 18 remembered what it was or not; correct? 19 A Yes. 20 Q Have you remembered what that third study was 21 since the last time we talked? 22 A Beyond knowing that it was something about 23 worsening and paradoxidal (sic) worsening. 24 Q Paradoxical worsening? Page 91 1 A Yes. I was refreshed to the title. 2 Q You were refreshed to the title in preparation 3 for the deposition today? 4 A No. 5 Q How were you refreshed to the title? 6 A In looking to see if I knew where those files 7 were. 8 Q Oh, okay. So when I asked you earlier if you 9 reviewed any documents in preparation for the 10 deposition today, you looked for documents but 11 you didn't find any? 12 A I found -- I showed people where they were. 13 Q I see. Okay. 14 A I didn't read them. 15 Q Okay. I'm sure you remember there was a little 16 controversy between Paul, Larry and I last time 17 about whether or not a rechallenge protocol had 18 been produced and there was some question, and 19 Larry had promised to look into it for us; 20 correct? 21 A Yes. 22 MR. MYERS: And I did. 23 MS. ZETTLER: I know you did. I 24 got a whole bunch of new documents, Larry. Page 92 1 Thank you. 2 MR. MYERS: You're welcome. 3 Q Was Larry able to produce those documents 4 because you were able to find them for him or 5 for somebody at Lilly? 6 A I was able to find them. 7 Q Were those documents produced or turned over to 8 the legal department prior to your being able 9 to find them since the last deposition? 10 A I don't know if they had been turned over. 11 These were still in a file. There could have 12 been other copies somewhere. 13 Q When you say these were still in the file, are 14 these in the file or were these in the file 15 that you still keep? 16 A No. 17 Q Where were they when you found them? 18 A They were down in the group that I used to work 19 in. 20 Q Last time we talked I believe you said that 21 your involvement with the studies was to help 22 draft the protocols; correct? 23 A Yes. 24 Q Also you did some budget estimate work on the Page 93 1 protocols? 2 A Yes. 3 Q And possibly at least ordered a study number? 4 A Yes. 5 Q Was that for each of the three protocols or 6 just for the rechallenge? 7 A I don't remember. 8 Q Did you work with Dan Russell on any of these 9 protocols? 10 A He had them for us. 11 Q And then he turned them over to you? 12 A Yes. 13 Q At what point in the process did he turn them 14 over to you? 15 A I recall they were very sketchy. 16 Q When you say "sketchy", you mean the protocols 17 themselves were very sketchy? 18 A Yes. 19 Q Do you remember what point in time he turned 20 them over to you? 21 A No. 22 Q Did looking for these documents, finding these 23 documents, refresh your recollection any as to 24 whatever responsibilities you had with regards Page 94 1 to the protocols themselves? 2 A Yes. 3 Q Can you give me an idea of what any of your 4 other responsibilities were. 5 A I recall that there had been a meeting about 6 the rechallenge protocol with outside 7 consultants. 8 Q Anything else? 9 A That was about it. 10 Q How many meetings do you recall having with 11 outside consultants? 12 A I believe one. 13 Q Do you recall meeting with any prospective 14 investigators, clinical investigators for any 15 of the trials? 16 A Only for Dr. Miller's trial. 17 Q Dr. Miller's trial is the validation of the 18 MSSI-R; right? 19 A Yes. 20 Q To your knowledge was that trial completed? 21 MR. MYERS: The Miller? 22 MS. ZETTLER: Dr. Miller's trial. 23 A Yes. 24 Q It was? When was it completed? Page 95 1 A I believe the CRA told me fairly recently. 2 Q What do you mean by fairly recently? 3 A Sometime in the last six months she mentioned 4 to me that that trial was ending. 5 Q Who is the CRA? 6 A Ellie Schatz. 7 Q We talked about her last time, right, 8 S-h-a-n-t-z? 9 A Yes. 10 Q Did she tell you what the results of that study 11 were? 12 A No. 13 Q Do you know if they were able to validate the 14 MSSI-R? 15 A No, I don't know. 16 Q How many investigators were on Dr. Miller's 17 study, clinical investigators? 18 A Dr. Miller was the clinical -- was the 19 investigator. 20 Q So it was just Dr. Miller? I'm sorry, I may 21 have misunderstood. Strike that. It's my 22 understanding that Dr. Miller developed the 23 MSSI-R; is that correct? 24 A Yes. Page 96 1 Q Okay. So it's your testimony that Dr. Miller 2 was the only clinical investigator on that 3 trial, the validation study? 4 A Okay. Let me clarify. There were 5 subinvestigators. 6 Q Okay. Were they all at the same site as 7 Dr. Miller? 8 A Yes. 9 Q Where is Dr. Miller's site located? 10 A Providence. 11 Q I was going to say New Hampshire, but I knew 12 that was wrong. How many subinvestigators did 13 he have? 14 A Maybe three or four. 15 Q Now, you said earlier that you recall one 16 meeting with outside consultants. Was that a 17 meeting regarding Dr. Miller's study or was 18 that a meeting regarding one of the other 19 protocols? 20 A I believe it was regarding a series of 21 protocols. 22 Q A series of protocols related to rechallenge? 23 A Yes. 24 Q When you say a series of protocols, you mean a Page 97 1 number of different drafts of the rechallenge 2 protocol or you mean a number of different 3 rechallenge protocols? 4 A The three protocols you're referring to. 5 Q So it regarded Dr. Miller's protocol, the 6 actual rechallenge, and the other paradoxical 7 deterioration study, I believe you said it was? 8 A Yes. 9 Q Was Dr. Miller's study an inpatient or an 10 outpatient study? 11 A Inpatient. 12 Q Were you involved in the study when enrollment 13 had been completed? 14 A No. 15 Q When was enrollment completed? 16 A Within the last six months I believe is when 17 she told me. 18 Q So it was an ongoing type of thing? 19 A Yes. 20 Q Had any inpatients been enrolled when you were 21 involved? 22 A Yes. 23 Q Did you have any responsibilities with regards 24 to the patients that were enrolled? Page 98 1 MR. MYERS: When you say 2 responsibilities, what do you mean? 3 Q Did any of your job duties on that protocol or 4 on Dr. Miller's study, I mean, have to do with 5 the patients; for instance, double-checking 6 CRFs, filling out adverse event forms? 7 A Yes. 8 Q Which one? 9 A I was the CRA responsible for the study. 10 Q What were your responsibilities as the CRA? 11 A Monitoring the trial, validating the data. 12 Q Anything else? 13 A Administrative duties. 14 Q Such as? 15 A Ordering supplies. 16 Q Anything else as far as administrative duties? 17 A Budgets. 18 Q Anything else? 19 A That's pretty general and it covers mostly 20 everything. 21 Q Besides monitoring the trial, validating data 22 and administrative duties, any other duties? 23 A Can you give me an example? 24 Q Well, for instance, adverse events. Were you Page 99 1 involved -- were you responsible for -- 2 A Yes. 3 Q Okay. Let me finish my question. 4 MR. MYERS: You asked her that 5 once. 6 MS. ZETTLER: Well, I was trying to 7 get -- there was two things. There was 8 something with CRFs and something with adverse 9 event and I wanted to make sure that I wasn't 10 confusing too much. 11 Q What were your duties regarding adverse events 12 that occurred during Dr. Miller's trial? 13 A Reporting them. 14 Q Anything else? 15 A Validating the ones that were reported. 16 Q When you say validating, what do you mean? 17 A Two parts, one was the source documents against 18 the case report forms and their accuracy, and 19 if there was any FDA regulations for me to 20 report serious ones, complying with those. 21 Q Do you recall reporting any serious adverse 22 events that occurred during Dr. Miller's trial? 23 A Yes. 24 Q What events? Page 100 1 A I remember a suicide. 2 Q During his trial? 3 A Yes. 4 Q I'm sorry, and you said these were hospitalized 5 patients? 6 A Yes. 7 Q Was a study drug used in this trial? 8 A No. 9 Q Were patients allowed to remain on the 10 medication, any medication that they were on 11 during the trial? 12 A Yes. 13 Q Was this suicide a Fluoxetine patient? 14 A I don't remember. 15 Q Was there any restriction that Fluoxetine users 16 could not be entered into the trial? 17 A No. 18 Q To your knowledge were there patients in that 19 trial that were on Fluoxetine? 20 A Yes. 21 Q How many patients were on that trial while you 22 worked on it? 23 A Approximately 25 patients. 24 Q Were there any suicide attempts besides the Page 101 1 completed suicide? 2 A Probably. 3 Q Why do you say probably? 4 A Because we were studying suicidal patients. 5 Q They were hospitalized. 6 A And I don't -- that doesn't preclude somebody 7 from acting out on a suicide. 8 Q Okay. But it's like you're making an 9 assumption that these people would commit 10 suicide or try to commit suicide. 11 A I remember reporting serious adverse events; 12 their nature I don't remember. 13 Q Do you recall how many serious adverse events 14 you reported out of those 25 people? 15 A Approximately all of them. 16 Q On one occasion each or more than one occasion 17 for each? 18 A I don't remember. 19 Q Did you fill out 1639s on all of those people? 20 A Yes. 21 Q Did you have any 3-day or 15-day alerts of 22 adverse events on those people? 23 A Yes. 24 Q In every case? Page 102 1 A No. 2 Q How many cases? 3 A The only one I recall is the suicide. 4 Q Was that a 3-day or a 15-day? 5 A I don't remember. 6 Q Was Dr. Miller surprised by the number of 7 serious adverse events during his trial? 8 A No. I believe I should clarify something. 9 Q Sure. 10 A The reason there was a large number of 1639s 11 reported for -- there were two situations: One 12 could be if you were on the trial and something 13 happened to you or if you were on the trial and 14 taking Prozac and something happened to you, or 15 if I read something in their charts either 16 prior to them coming into the trial or after 17 their trial and they had been taking a Lilly 18 drug, I was required to report those as 1639s, 19 but those went in under our spontaneous 20 reporting system. 21 Q Okay. The ones that happened prior or after 22 the trial? 23 A Yes. 24 MR. MYERS: Well, let me just Page 103 1 understand something. I'm having trouble. You 2 said there were 25 patients while you were the 3 CRA on the trial? 4 THE WITNESS: Yes. 5 MR. MYERS: Were there patients 6 enrolled after you went off and the other 7 person became a CRA? 8 THE WITNESS: Yes. 9 MR. MYERS: So there were more than 10 25 patients in the trial? 11 THE WITNESS: Yes. 12 MR. MYERS: Okay. I'm sorry. I 13 just -- 14 MS. ZETTLER: That's okay. 15 Q But it's still your testimony that you filled 16 out a 1639 on just about everybody in the trial 17 under one of those three categories you just 18 talked about? 19 A Yes. 20 Q And you do recall serious adverse events 21 occurring to patients while they were on the 22 trial; correct? 23 A Yes, but -- 24 Q And do you recall serious -- Page 104 1 MR. MYERS: I don't think she was 2 finished. 3 MS. ZETTLER: Oh, I'm sorry. 4 A But the ones that reported via the spontaneous 5 system don't have to meet the same serious 6 criteria. 7 Q But I'm talking about on the trial itself. 8 A On the trial. 9 Q Okay. Let's make sure we're clear on this 10 because I think I'm getting confused. Your 11 testimony is that there were three situations 12 where you would be obliged to report an adverse 13 event, an adverse event during the trial; 14 right? 15 A Yes. 16 Q One is if it's an adverse event that occurred 17 while the person was participating in the 18 actual trial? 19 A Yes. 20 Q For instance, the suicide that occurred during 21 the trial; correct? 22 A Yes. 23 Q Okay. The next one is if the person was 24 participating on the trial and taking Prozac? Page 105 1 A Yes. 2 Q Okay. Now, why is that different than -- why 3 are you differentiating between that and the 4 person being on the trial? 5 A I probably noted it differently on the 1639 6 because it would be difficult to report -- the 7 system -- the reporting mechanism is different. 8 I wanted them reported even though there was no 9 study drug used in this study. I wanted them 10 reported because of the event itself while some 11 1639s on trial go in and they go in under a 12 certain drug code. 13 Q Okay. So when you say you wanted it reported 14 even though no study drug was used, you're 15 talking about a situation where the person is a 16 participant in the trial? 17 A Yes. 18 Q But not on Prozac? 19 A Yes. 20 Q And then the other -- 21 A Or an active comparator to Prozac. 22 Q Okay. And then the other situation is where 23 the person is on the trial taking Prozac? 24 A Yes. Page 106 1 Q Now, how would that be reported differently 2 from the person on the trial who was not on 3 Prozac or another drug? 4 A I would write that -- under study drug I would 5 put I believe Prozac down so it would go into 6 the (quote) Prozac database in DEN. 7 Q Okay. So it's more of a differentiation for 8 Lilly's record keeping as opposed to reporting 9 to the FDA? 10 A Yes. 11 Q You would still have to report adverse events 12 that happened on the trial to the FDA 13 regardless of what drug or any drug that the 14 person was on? 15 A Based on their serious criteria. 16 Q Right. And then the third category which were 17 reported more as spontaneous adverse events 18 were those events that occurred either prior to 19 the person being admitted into the trial or 20 after the person had completed the trial; 21 correct? 22 A Correct, if they were on a Lilly drug. 23 Q Okay. And you recall filling out adverse 24 events -- strike that. You recall adverse Page 107 1 events occurring in each of these three 2 categories; correct? 3 A Yes. 4 Q And it encompassed in one way or another every 5 person that was involved in the study, each of 6 those approximately 25 people that were on the 7 study when you were working on it? 8 A Based on my recollection it appears -- my 9 recollection is that a large number received 10 met one of those three criteria. 11 Q Approximately how many of those 25 people were 12 taking Prozac? 13 A I don't recall. 14 Q Can you give me an idea? 15 A No. 16 Q Can you give me an estimate? 17 A No, I can't. 18 Q Was it more than half? 19 A I don't remember. 20 MS. ZETTLER: Do you want to take a 21 break. I saw you looking at your watch. 22 THE WITNESS: Yes. 23 (A brief recess was taken.) 24 Q How long did you work on Dr. Miller's study? Page 108 1 A Could you clarify that? 2 Q No, I can't. From the -- 3 MR. MYERS: Until what point in 4 time? 5 MS. ZETTLER: Yes. 6 A Till about August of '92. 7 Q Okay. And when did you start working on it? 8 A About July or August of '91. 9 Q So the total time you worked on it was 10 approximately a year, maybe a little more than 11 a year? 12 A Yes. 13 Q How long did you work on the study? Strike 14 that. When within that one-year period of time 15 did Dr. Miller start recruiting patients for 16 the study? 17 A In September. 18 Q Of '91? 19 A Yes. 20 Q The 25 patients or the approximately 25 21 patients that you talked about were patients 22 that were all recruited at the same time or 23 over that almost one-year period? 24 A Over that almost one-year period. Page 109 1 (Deposition Exhibit 13 was marked for 2 identification and a discussion was held 3 off the record.) 4 Q While Larry's looking at Exhibit 13, let me ask 5 you this real quick. At any given time during 6 that one-year period where there were patients 7 that were actually participating in 8 Dr. Miller's trial, what was the largest number 9 of patients at any given time that he had 10 recruited? 11 A I don't remember. 12 Q Was it more than five? 13 A I don't believe so. 14 Q And what was the period of time that each 15 patient was to participate in the trial? 16 A Seven weeks, I think. 17 Q Okay. Go ahead and take a look at that 18 (indicating). 19 A (Witness complies). 20 Q Have you had a chance to look at Exhibit 13 21 A Yes. 22 Q Do you recognize the pages that make up that 23 exhibit? 24 A Yes. Excuse me, not the last page. Page 110 1 Q Okay. I apologize. I don't even know how that 2 one got in there. 3 MR. MYERS: Shall we remove it? 4 MS. ZETTLER: Yes, take it off. 5 Q Now, do you recognize all the pages of 6 Exhibit 13? 7 A Yes. 8 Q Can you tell me what it is or what they are. 9 A They're the initial draft of the 1639s that was 10 sent to the Drug Epidemiology Unit. 11 Q On the first page of the exhibit it says "Upon 12 review of CRF data" -- and in parens it states 13 (B1Y-MC-S002) -- "it was noted that the patient 14 had taken an overdose of Prozac, Ativan, 15 Naprosyn", et cetera; correct? 16 A Yes. 17 Q B1Y-MC-S002 is Dr. Miller's study, is it not? 18 A Yes. 19 Q Is this one of those situations that you were 20 explaining to us earlier where you would fill 21 out a 1639 for somebody on the study itself; in 22 other words, an adverse event that occurred 23 during the study itself? 24 A Yes. Page 111 1 Q Towards the bottom of the page it says 2 manufacturer control number. 3 A Yes. 4 Q Again, this is the control number that would be 5 used on the 1639 that is sent to the FDA; 6 correct? 7 A Yes. 8 Q And also this is the number that you would 9 search under DEN if you wanted to get DEN 10 information about this patient; correct? 11 A Yes. 12 Q The next page though, is that related to the 13 first page? 14 A It's difficult to confirm that these two -- 15 they look like they belong together. 16 Q On the first page it says date received by 17 manufacturer, February 28th, 1992; correct? 18 A Yes. 19 Q And then on the second page it also has at the 20 bottom of the page by your signature, date 21 February 28th, 1992; correct? 22 A Yes. 23 Q Is that your handwriting on the second page? 24 A By my signature, yes. Page 112 1 Q How about towards the top? 2 A The onset date? 3 Q Yes. Is that yours? 4 A Yes. 5 Q How about the actual event terms? 6 A The one under the cross-out looks like it was 7 mine. 8 Q So when it says on the first event Actual Term, 9 overdose -- 10 A Yes. 11 Q -- and COSTART Term, suicide attempt -- 12 A Yes. 13 Q -- that that is your handwriting? 14 A Yes. 15 Q And did you cross that out? 16 A I don't -- I don't know. 17 Q The second part, the uncrossed-out part that 18 says under Actual Term, suicide attempt, and 19 under COSTART Term, overdose, that is not your 20 handwriting? 21 A I don't think so. 22 Q Do you recognize that handwriting? 23 A No. 24 Q Do you remember this Event Terms sheet? Page 113 1 A No. 2 Q Do you know why somebody crossed out what you 3 wrote under Actual Term and COSTART Term and 4 changed those terms? 5 A Because I probably had them backwards. 6 Q Do you know if in February of 1992 Lilly was 7 using the COSTART dictionary or the ELECT 8 dictionary? 9 A I believe they were using a COSTART dictionary. 10 Q When did they start using COSTART? 11 A I don't remember. 12 Q Was it before or after you started working on 13 Dr. Miller's study? 14 A Before. 15 Q Was it before or after you were involved in the 16 O.U.S. data collection project? 17 A I don't remember. 18 Q On the right-hand side of the page there is 19 some initials. 20 MR. MYERS: The second page again? 21 MS. ZETTLER: Yes. 22 Q Do you see that? 23 A Yes. 24 Q Are those your initials? Page 114 1 A No. 2 Q Do you know whose initials they are? 3 A No. 4 Q Could they be Dr. Thompson's initials? 5 A They could be. 6 Q Are you familiar with Dr. Thompson's 7 handwriting? 8 A Only based on his signature below here. 9 Q Do you recognize that as his signature? 10 A Yes. 11 Q Did you fill out the bottom part of this where 12 it says "Follow-up Required? No"? 13 A Where? 14 Q At the bottom of the sheet on the second from 15 the bottom line where it says "Follow-up 16 Required? Y, N" and "N" is circled? 17 A No, I don't complete that section. 18 Q Who completes that section? 19 A The physician. 20 Q How about towards the top again under the first 21 event, there is a box next to the blackened box 22 on the left. It says "If event is serious, is 23 it expected?" Did you fill out that portion? 24 A No. Page 115 1 Q Who would fill that out? 2 A The physician. 3 Q In your opinion is a suicide attempt using an 4 overdose of drugs a suicide attempt or an 5 overdose? 6 MR. MYERS: Well, before she 7 answers, let me object to the form. That's a 8 medical question. 9 MS. ZETTLER: I asked her opinion, 10 not a doctor's opinion. 11 MR. MYERS: And I understand. And 12 by its very nature that calls for a medical 13 opinion. 14 Q You can answer it, Catherine. 15 MR. MYERS: If you can answer it, 16 answer it. 17 Q In your opinion is a suicide attempt using 18 drugs a suicide attempt? 19 A Try that again. 20 Q Sure. In your opinion is a suicide attempt 21 using drugs -- like in other words, taking an 22 overdose of drugs -- is that a suicide attempt? 23 MR. MYERS: Same objection. If you 24 can answer it, go ahead and answer it. Page 116 1 A Based on the question that you just asked me 2 and the way it was phrased, my answer would be 3 I would consider it a suicide attempt if a 4 suicide attempt was attempted with drugs. 5 Q Is an overdose always a suicide attempt in your 6 opinion? 7 MR. MYERS: Same objection. You 8 can answer if you can. 9 A In my opinion an overdose is not always a 10 suicide attempt. 11 Q The third page of the exhibit, Exhibit 13, 12 could you tell me what that is. 13 A It's the initial draft copy of a 1639 for a 14 spontaneous report. 15 Q Is this your handwriting under "Describe 16 Event(s)" section? 17 A Yes. 18 Q And the page after that, to your knowledge is 19 that related to the drug experience report 20 working form? 21 A Based on the event listed and the date of my 22 signature, they look as if they are related. 23 Q Is that your handwriting under the first event? 24 A "Cut wrist" and the date is mine and my Page 117 1 signature. 2 Q How about the COSTART Term of suicide attempt, 3 is that your handwriting? 4 A No. 5 Q And again did you assign the expectancy to this 6 event? Did you fill out that portion of the 7 form where it asks "If the event is serious, is 8 it expected"? 9 A No. 10 Q That would have been Dr. Beasley in this case? 11 A Yes. 12 Q Do you know why Dr. Beasley would have marked a 13 suicide attempt by slicing a wrist expected? 14 MR. MYERS: Well, before she 15 answers, let me object to the form. That calls 16 for her to speculate as to why he made that 17 designation. Only he knows. If you know, tell 18 her. 19 A In my opinion expectancy as it says here is 20 compared to the package insert. 21 Q So in the package insert in May of 1992 it 22 talks about suicide attempts, is that what 23 you're saying? 24 A Yes. According to -- if I was reading this Page 118 1 now, yes, I would assume that that's the 2 package insert. 3 Q How is saying that this adverse event is 4 expected impact on reporting this adverse event 5 if in any way? 6 A I think when it's received by the FDA, it's 7 classified differently. 8 Q In what way? 9 A I don't know the exact terminology or criteria 10 that the FDA uses. 11 Q How about how it's stored in the DEN 12 dictionary -- or I'm sorry -- in the DEN 13 database? 14 A The same way. 15 Q Simply because it's considered serious? 16 MR. MYERS: Let me object to the 17 form. You've now switched gears from expected 18 to serious. 19 MS. ZETTLER: Right. 20 A In my knowledge there is a couple of different 21 criteria: One is serious and expected and 22 others are serious and unexpected events. And 23 their reporting requirements and the place in 24 which they are stored or how they are stored Page 119 1 could be different. 2 Q To your knowledge are serious expected adverse 3 events stored in the DEN database? 4 A Yes. 5 Q Regardless of whether or not they're on 6 clinical trials? 7 A Yes. 8 Q It's your testimony that to your understanding 9 the way it's treated by the FDA is different 10 depending on the expectancy; correct? 11 A I believe so. 12 Q Please turn back to the first page. 13 A (Witness complies). 14 Q Other than at the bottom where it says "Please 15 send copy of report to C. Mesner, DC 2128", is 16 there any other way you can tell who filled out 17 this form from the form itself? 18 A On Page 2 it says "Report prepared by". 19 Q So both these pages comprise the same report? 20 A As I testified to earlier, it looks based on 21 the dates and what was reported that this is 22 Page 2 of this Page 1 (indicating). 23 Q But I mean as far as the actual form, the drug 24 experience report working form, is the Event Page 120 1 Term sheet part of that form as a rule? 2 A Yes. 3 Q Okay. Is there any other portions of this form 4 that aren't in this exhibit? 5 A Not that I'm aware of. 6 Q Do you know why Dr. Thompson on the first 7 instance would not require a follow-up on this 8 adverse event? 9 MR. MYERS: Well, I object to the 10 form. That calls for a medical opinion and 11 calls for her to speculate as to why he 12 presumably made that designation. If you know, 13 you can certainly answer. 14 A I don't know. 15 Q Did Lilly have a criteria under which they 16 would decide whether or not a certain adverse 17 event should be followed up or not? 18 A Sometimes you prepare a report with very 19 preliminary information in order to get the 20 report into the system as soon as possible and 21 you don't quite know all the lab results. Or, 22 for example, you knew a patient was admitted to 23 the hospital to have surgery, you don't know 24 the outcome of the surgery yet. Page 121 1 Q And in those cases you would follow up? 2 A Yes. 3 Q If you felt you had enough information upon the 4 initial report though, you wouldn't necessarily 5 follow up? 6 A I think that's true. 7 Q On the first page there is a stamp in the 8 bottom right-hand corner. It looks like it 9 says "VLH, March 3, '92". Do you know who that 10 is or what that is? 11 A No, I don't. 12 Q Do you know anybody with the initials VLH? 13 A Not offhand, no. 14 Q Would the reporter on these forms be Dr. Miller 15 or somebody working with Dr. Miller? 16 A If all of these forms are S002, yes. 17 Q Did you have a file in which you kept all of 18 your working forms from the S002 study? 19 A They would be kept in the patient file. 20 Q Did you have in your files at Lilly files on 21 every patient that was included in this study? 22 A I didn't store my files in my office. 23 Q But did you keep your own file on each patient 24 that was entered into Study S002? Page 122 1 A No. 2 Q Did you keep files of these adverse event 3 reporting forms? 4 A I don't remember if I kept a separate book of 5 1639s for that study or if I just automatically 6 filed them with the patient file. 7 Q Where was the patient file kept? 8 A In our document control area after they were 9 validated. 10 Q After they were validated and entered into the 11 computer database? 12 A Yes. 13 Q Do you know, to your knowledge was there a 14 computer database that was used to store data 15 from S002? 16 A Yes, I believe there was. 17 Q Did you ever meet personally with Dr. Miller? 18 A Excuse me? 19 Q Did you ever meet personally with Dr. Miller? 20 A Yes. 21 Q On how many occasions? 22 A I probably visited their site five or six 23 times. 24 Q Prior to the study being initiated after the Page 123 1 protocol was completed and, you know, prior to 2 the patients being enrolled, did you meet with 3 Dr. Miller? 4 A I believe I met with Dr. Miller prior to the 5 study beginning once or twice. 6 Q For what purposes? 7 A To go over his teaching materials and his scale 8 and to review his budgets and how we were 9 planning on setting them up. 10 Q When you say "setting them up", what do you 11 mean, the scales, the budget, the study? 12 A Because he was going to be making some training 13 videos, et cetera, and I was setting up those 14 budgets differently than I would be setting up, 15 for example, a study budget. 16 Q To your knowledge were those training videos 17 ever made? 18 A To my knowledge, no. 19 Q Why not? 20 A I think they were to be made to continue to 21 teach people the MSSI-R and since we hadn't 22 validated it at the point when I left the 23 study, I don't think they had been made. 24 Q Do you know if it was made after you left the Page 124 1 study? 2 A No, I don't. 3 Q When you say you hadn't validated the scale 4 when you had left the study, what do you mean? 5 Is it that you were incapable of validating it 6 or it just hadn't been validated at that point? 7 A It had not been validated at that point. 8 Q To your knowledge was it ever validated? 9 A To my knowledge I don't know. 10 Q The other CRA that took over after you left, 11 Ellen Schantz -- 12 A Schatz. 13 Q -- did she ever talk to you about the number of 14 adverse events that she was reporting on the 15 S002 study? 16 A No. 17 Q Did she ever tell you whether or not they were 18 able to validate the scale? 19 A No. 20 Q Did you ask her? 21 A No. 22 Q To your knowledge had Dr. Miller ever worked 23 with Eli Lilly before on Fluoxetine? 24 A Not to my knowledge. Page 125 1 Q Was he working on any other studies besides the 2 validation study at the time he was working on 3 the validation study; in other words, was he 4 working on any other studies at that time? 5 A Could you clarify that? 6 Q Sure. You said to your knowledge he had never 7 worked with Lilly prior to working on the 8 validation study; correct? 9 A To my knowledge, he had not. 10 Q Okay. To your knowledge was he working with 11 Lilly on any other studies besides the 12 validation study while he was working on the 13 validation study? 14 A To my knowledge he was not working for Lilly on 15 any other study during that time. 16 Q Was he working for anybody on behalf of Lilly? 17 A Not that I was aware of. 18 Q To your knowledge did he work -- other than 19 developing the scale for rating the 20 suicidality -- did he do any other work on the 21 rechallenge protocol? 22 A I believe he acted as a consultant on the 23 rechallenge protocol because it contained a 24 piece of his scale. Page 126 1 Q When you say "a piece of his scale", what do 2 you mean? 3 A I'm sorry. It contained -- his scale was a 4 piece of the protocol. 5 (Deposition Exhibit 14 was marked for 6 identification.) 7 Q Have you had a chance to take a look at 8 Exhibit 14? 9 A Yes. 10 Q Do you recognize this? 11 A Yes. 12 Q Can you tell me what it is? 13 A It's Dr. Miller's protocol. 14 Q Is this the final draft of the protocol? 15 A I don't know. 16 Q At the bottom of the first page it says 17 "Investigator information, multicenter, 18 investigators to be determined". I believe it 19 was your testimony that Dr. Miller's site was 20 the only site that was used on the protocol; 21 correct? 22 A Yes. 23 Q Does that refresh your recollection as to 24 whether or not this is the final draft of the Page 127 1 protocol? 2 A No. 3 Q Do you know why they decided to go from a 4 multicenter study to just using Dr. Miller's 5 site? 6 A Because Dr. Miller didn't have any training 7 materials to train the other sites to my 8 knowledge. 9 Q Do you know if this protocol was submitted to 10 the IND for approval? 11 A I know that S002 was submitted to the IND for 12 approval. I don't know if Exhibit 14 is the 13 one that was submitted. 14 Q Is it your understanding that the FDA approved 15 S002? 16 A Yes. 17 Q On the third page of the exhibit under Section 18 3.9 it says "Efficacy and Safety Evaluation". 19 Efficacy and safety of what? 20 A It was probably just an error and that's the 21 protocol format that we use. 22 Q Was Dr. Miller's study being used to a certain 23 extent as a pilot study for the rechallenge 24 protocol? Page 128 1 A To a certain extent one might consider that 2 since the scale was -- a valid scale needed to 3 be used. 4 Q To your knowledge is the results of 5 Dr. Miller's study the reason why the 6 rechallenge study was never performed? 7 A Could you clarify that? 8 Q Sure. Was what was happening during 9 Dr. Miller's study with regards to those 10 patients who were on Fluoxetine or other 11 antidepressants on Dr. Miller's study, were the 12 results of those patients' experiences in the 13 trial the reason why the rechallenge study was 14 never done to your knowledge? 15 A To my knowledge, no. 16 Q To your knowledge why was the rechallenge study 17 not done? 18 A The primary efficacy tool, the MSSI-R, needed 19 to be validated prior to starting the study. 20 Q To your knowledge are they going to start the 21 study now that Dr. Miller's trial is complete? 22 A I've not been assigned to that role in over a 23 year. I don't know what the direction of that 24 department is. Page 129 1 Q You haven't heard anything through the 2 grapevine at Lilly as to whether or not they 3 are going to do the rechallenge protocol? 4 A No. I'm very disconnected from the medical 5 component in that respect. 6 Q Do you have any connections with Taiwan in your 7 present position, affiliates in Taiwan? 8 A Vague connections. 9 Q Do you have any connection with clinical 10 investigators in Taiwan? 11 A No. 12 Q Are you familiar with a Dr. Lu from Taiwan, 13 L-u? 14 A No. 15 Q Is it your understanding that the FDA was 16 promised that initial information on the -- 17 strike that. Is it your understanding that the 18 FDA was promised initial results of a 19 rechallenge study in early 1992? 20 A No. 21 Q Were you aware that in May of 1991 there was a 22 meeting between Lilly employees and the FDA 23 regarding rechallenge? 24 A Yes. Page 130 1 Q Did you attend that meeting? 2 A No. 3 Q How is it that you became aware of the meeting? 4 A People in my immediate area were attending that 5 meeting. 6 Q Who attended that meeting to your knowledge? 7 A I think the physicians. 8 Q Which physicians? 9 A Probably Beasley and Heiligenstein, Wheadon or 10 Kotsanos. 11 Q Did you work with Dr. Kotsanos on the 12 rechallenge protocol? 13 A I don't think so. 14 Q Do you know what Dr. Kotsanos' involvement in 15 the rechallenge protocol or rechallenge study 16 was? 17 A No. 18 Q Are you aware that Lilly agreed -- or strike 19 that. Are you aware that the FDA was promised 20 that Lilly would be ready to proceed with the 21 rechallenge protocol in September of 1991? 22 MR. MYERS: I'll object to the form 23 of the question. I think that assumes a fact 24 that's not going to be in evidence. But if you Page 131 1 know, tell her. 2 A Could you repeat the question? 3 Q Sure. 4 MS. ZETTLER: Let me just mark 5 that. 6 (Deposition Exhibit 15 was marked for 7 identification.) 8 Q Are you familiar with that exhibit, Catherine? 9 A Having looked at it now, yes. 10 Q Are you aware that on May 13th, 1991 employees 11 of Lilly promised the FDA that they would have 12 the rechallenge protocol ready to go by 13 December of 1991? 14 A No. Prior to reading this, no. 15 Q Are you aware of that now? 16 A Yes. 17 Q And they also agreed to provide data after the 18 first quarter of 1992 that would provide 19 information on six months of experience; 20 correct? 21 A Yes. 22 Q That didn't happen, did it? 23 A Not to my knowledge. 24 Q Why not, if you know? Page 132 1 A Because the rechallenge protocol did not begin 2 by September 1st. 3 Q And the rechallenge protocol hasn't at least to 4 your knowledge begun to this day, has it? 5 A No, it has not to my knowledge. 6 Q To your knowledge has the MSSI-R ever been 7 incorporated into U.S. or United Kingdom 8 clinical trials? 9 A To my knowledge, no. 10 Q Have you ever dealt with Dr. Jonathan Cole? 11 A Yes. 12 Q In what capacity? 13 A In my first assignment I was responsible for 14 monitoring a study of his. 15 Q A clinical trial on Fluoxetine? 16 A Yes. 17 Q Was that a depression trial? 18 A I don't remember. 19 Q Where was that trial located? 20 A McLean Hospital. 21 Q Who is Barbara Stanwick? 22 A I don't know. 23 MR. MYERS: Are you reading from 24 something? Page 133 1 MS. ZETTLER: Yes. She's reading 2 from the same thing. Off the record. 3 (A discussion was held off the record.) 4 MS. ZETTLER: Back on. 5 Q So you don't know if they mean -- if Barbara 6 Stanwick referred to in the second page of the 7 exhibit is a physician; correct? 8 A I do not know. 9 Q Other than the actress Barbara Stanwick, do you 10 know of anybody named Barbara Stanwick? 11 A No. 12 Q Under that same section, Section 3, the second 13 bullet point, it says "The FDA also suggested 14 testing the questionnaire in hospitalized 15 patients with depression to both further 16 validate the instrument and determine if the 17 phenomena exists in a more seriously 18 ill-population." Had there been a preliminary 19 validation of Dr. Miller's scale to your 20 knowledge? 21 A Not to my knowledge. 22 Q Did you ever deal with Dr. Cole with regards to 23 Dr. Miller's study? 24 A No. Page 134 1 Q Was he included as an investigator on 2 Dr. Miller's study to your knowledge? 3 A No, he was not. 4 Q Was he approached to be an investigator on the 5 rechallenge study to your knowledge? 6 A Not that I'm aware of. 7 Q How about Dr. Teicher, have you ever spoke with 8 Dr. Teicher? 9 A I've never spoken to Dr. Teicher. 10 Q Have you ever communicated with him in any way? 11 A Not that I'm aware of. 12 Q Do you know if Dr. Teicher was consulted with 13 regards to the MSSI-R? 14 A I don't -- I don't recall. 15 Q To your knowledge was the MSSI-R ever given by 16 Lilly to other drug companies to use in their 17 clinical trials? 18 A Not that I'm aware of. 19 Q Did you ever order the drugs to be used in the 20 rechallenge study? 21 A I don't remember. 22 Q Would you have done that if you didn't intend 23 on conducting the study? 24 A I would have ordered the CT material as soon as Page 135 1 I knew the basic outline of the protocol. 2 Q Is that common practice at Lilly when the basic 3 outline of the protocol is written to order the 4 CT materials? 5 A When you're fairly sure, yes. 6 Q When you say CT material, what does that 7 encompass? 8 A Clinical trial material. 9 Q And you're talking about the drugs, the 10 placebo, the comparator and the study drug? 11 A Yes. 12 Q Anything else? 13 A No. 14 Q How long was the retrial challenge protocol 15 supposed to last, the rechallenge study? 16 A I don't remember. 17 Q At one point the title of the rechallenge study 18 was changed from Fluoxetine/Desipramine/Placebo 19 suicidality rechallenge to the Alternative 20 Treatment Study; correct? 21 A I know the title had been changed. 22 Q Do you know why the title was changed? 23 A Probably because it didn't meet the 24 60-character limit we're allowed. Page 136 1 Q You mean it went over the 60-character limit? 2 A It could have. 3 Q Do you recall the names of any of the 4 investigators that were approached to work on 5 the rechallenge protocol? 6 A No. 7 Q How about Dr. David Dunner? 8 A I know of Dr. David Dunner, but I don't know if 9 he was approached. 10 (Deposition Exhibit 16 was marked for 11 identification.) 12 Q Have you had a chance to look at Exhibit 16? 13 A Yes. 14 Q Does that refresh your recollection as to 15 whether or not CT materials were ordered for 16 the rechallenge study? 17 A Provided that the Fluoxetine alternative study 18 and the rechallenge were one and the same, yes, 19 this is a CT order. 20 Q The study number for the rechallenge protocol 21 was B1Y MC HCFQ; correct? 22 A Yes. 23 Q And that's what is listed on the first page 24 here; isn't it? Page 137 1 A Yes. 2 Q For the project? 3 A Yes. 4 Q So that would indicate that these were CT 5 materials that were being ordered for the 6 rechallenge protocol? 7 A Yes. 8 Q What's a CTOM order, is that different than a 9 CT order? 10 A CTOM is the -- I believe it's the name of the 11 system used to order CT materials by the 12 operations group. 13 Q Under the date it says requested October 8, 14 1991; needed November 15th, 1991. 15 A Yes. 16 Q Does that indicate to you when they intended to 17 start the study? 18 A On November 15th. 19 Q Do you know why it wasn't started on 20 November 15th? 21 A As I testified to earlier, I believe the only 22 reason it was not started was that we didn't 23 have a valid scale to start with. 24 Q Was it expected that Dr. Miller's scale would Page 138 1 be validated by November 15th? 2 A No, it was not. 3 Q And his study started in -- was it September of 4 1991? 5 A Yes. 6 Q And if it wasn't expected that the trial or 7 that the scale would be validated by that date, 8 then why were the drugs ordered and why was it 9 stated that they were needed by November 15th? 10 A I don't know. 11 (Deposition Exhibit 17 was marked for 12 identification.) 13 Q Do you recognize this exhibit? 14 A Yes. 15 Q Can you tell me what it is. 16 A It's the handwritten request for CT materials 17 that the CRA completes and provides to CT ops. 18 Q So before the CTs were ordered in Exhibit 16, 19 you ordered them as reflected in Exhibit 17; 20 correct? 21 A Yes. 22 Q And I think you testified earlier that you 23 ordered them because you were reasonably sure 24 that the protocol was going to proceed? Page 139 1 A Yes. 2 Q Were you told to cancel the order? 3 A I don't remember. 4 Q Was there any reason why somebody else would 5 have ordered the materials in October of '91? 6 A Let me clarify that this is the order that we 7 placed and Exhibit 16 is the order once 8 received by CT ops they put in the CTOM system, 9 and it's clear to me now that this order while 10 I placed it in July did not go into their CT 11 order until October. 12 Q Is that typical? 13 A Not now, but it was in the past. 14 Q Was it typical at this time? 15 A Yes. 16 Q Why? Why did it take so long? 17 A Because they were backlogged. 18 Q For three months, four months? 19 A Yes. 20 Q On the second page of the exhibit it says Core 21 Study, and then underneath that is listed 1, 2 22 and 3. It says total time to enroll and 23 medicate all patients, twelve months; estimated 24 completion date, June '93; correct? Page 140 1 A Yes. 2 Q When it says estimated completion -- or I'm 3 sorry -- total time to enroll and medicate all 4 patients, twelve months, when did you 5 anticipate that this trial was going to begin? 6 A My anticipation probably when I filled out the 7 study was as soon as I could get CT material. 8 Q But those dates don't jibe, do they? 9 MR. MYERS: Which dates? 10 MS. ZETTLER: The completion date 11 of June of 1993 with the total time to enroll 12 and medicate all patients being twelve months 13 and the initial order being put in 14 approximately two years earlier. 15 A It sometimes takes six or eight months to get 16 CT materials, especially a comparator drug. 17 Q When you order a comparator drug, who do you 18 order it from, the comparator drugs 19 manufacturer? 20 A Yes. 21 Q Is that common for a manufacturer of a 22 comparator drug to sell a competitor a drug to 23 test? 24 A Yes. Page 141 1 Q Does Lilly sell Fluoxetine to other companies 2 to test against their drugs? 3 A I believe they perhaps probably do. 4 Q Have you ever heard of a situation where Lilly 5 has sold another company drugs, Fluoxetine, to 6 test on indications other than depression? 7 A Not that I'm aware of. 8 Q Have you ever heard of Lilly buying drugs from 9 other companies to test on other stuff, other 10 indications for Fluoxetine other than 11 depression? 12 A I'm sorry. Could you repeat that? 13 Q Sure. Let me ask you this. Let me ask it this 14 way: To your knowledge has Lilly tested 15 Fluoxetine for use in treatment of indications 16 other than depression using another company's 17 drug as a comparator? 18 MR. MYERS: Along with Fluoxetine 19 as a study drug? 20 MS. ZETTLER: Right. Right. 21 A I'm sorry. I must just be getting tired. I 22 don't understand. 23 Q That's all right. You've worked on Lovan, 24 haven't you? Page 142 1 A No, I have not. 2 Q You've worked on Fluoxetine for uses in other 3 than depression; right? 4 A As a CRA, I worked on it for other than 5 depression. 6 Q Did you work on any clinical trials that were 7 comparator trials comparing Fluoxetine against 8 another company's drugs? 9 A Yes. 10 Q In those situations then would you order the 11 other company's drug from the company for that 12 study? 13 A Yes. 14 Q Were you obligated or were you asked by the 15 other company to tell them why you wanted to 16 purchase some of the drug? 17 A Yes. 18 Q And to your knowledge has that happened or vice 19 versa; in other words, has, say another company 20 like Abbott called you and said, "We'd like to 21 use Fluoxetine as a comparator drug in a study 22 of one of our drugs", such and such? 23 A They wouldn't contact me. They would contact 24 the purchasing or the CT areas. Page 143 1 Q Is it fair to say that if Abbott or some other 2 drug company did a comparator study using 3 Fluoxetine compared to their drug for an 4 indication other than depression, the most 5 likely source of the Fluoxetine would have been 6 Lilly? 7 MR. MYERS: I object to the form. 8 She said she didn't know if they sold it for 9 that purpose, so how could she know what the 10 source is. If you know, tell her. 11 A I wouldn't know how somebody could get 12 Fluoxetine other than getting it through us or 13 a pharmacy. 14 Q Have you ever heard of a pharmacy distributing 15 a competitor's drug to another competitor for 16 use in a clinical trial without the company's 17 permission? 18 A My understanding is that anybody can purchase a 19 drug with a prescription and use it any way 20 they want to. 21 Q Has Lilly ever sought prescriptions from 22 doctors so they could acquire drugs to use in 23 clinical trials? 24 A Not that I'm aware of. Page 144 1 THE WITNESS: I need to take a 2 break. 3 MS. ZETTLER: Sure. 4 (A brief recess was taken.) 5 Q To your knowledge was Dr. Miller's scale ever 6 used in any other clinical trial conducted by 7 Lilly? 8 A Not that I'm aware of. 9 Q Are you familiar with study HCFP? 10 A No. 11 Q Are you familiar with a gentleman named Mario 12 Savellini (phonetic) or Savelloni? 13 A Yes. 14 Q Who is Mario? 15 A He's a CRC in the New England area. 16 Q I'm sorry, in the what area? 17 A New England. 18 Q How do you say his last name, Savelloni? 19 A Savelloni. 20 Q Savelloni, okay. Did Mr. Savelloni work on the 21 rechallenge protocol or rechallenge study to 22 your knowledge? 23 A He is responsible for Dr. Miller's site, that 24 falls in his territory. Page 145 1 Q How about the rechallenge study, was he 2 involved in that? 3 A He was involved from a CRC perspective. 4 Q To your knowledge did he recruit any 5 prospective investigators for that study? 6 A Not other than Dr. Miller. I'm sorry, the 7 rechallenge or Miller's study? 8 Q The rechallenge. 9 A I don't know if physicians were recruited or 10 not. 11 Q You testified earlier that you recall that 12 there was a meeting of outside consultants with 13 regards to the rechallenge; correct? 14 A Yes. 15 Q To your knowledge were any of those outside 16 consultants to be used as clinical 17 investigators if the rechallenge study had been 18 performed? 19 A I don't know the answer to that question. 20 (Deposition Exhibit 18 was marked for 21 identification.) 22 Q Have you had a chance to look at Exhibit 8? 23 MR. MYERS: 18. 24 Q I'm sorry, Exhibit 18? Page 146 1 A Yes. 2 Q Do you recognize the letters comprising 3 Exhibit 18? 4 A Yes, I do. 5 Q Are those the letters that you sent out with 6 regards to the meeting that you told me earlier 7 you recalled? 8 A Yes. 9 Q And this was a meeting that was related 10 particularly to the rechallenge study; correct? 11 A Now that I read this letter, yes. 12 Q The first and second pages of that exhibit are 13 essentially the same letter; correct? 14 A Yes. 15 Q To different people? 16 A Probably. Yes. 17 Q And it talks about a meeting that's held on 18 August 7, 1991 at the Holiday Inn Airport in 19 Indianapolis; correct? 20 A Yes. 21 Q Now, the third page of the exhibit talks about 22 an additional meeting that's being held on 23 August 8th; correct? 24 A Yes. Page 147 1 Q Why were some of these people invited to the 2 August 7th meeting and some of them invited to 3 both? 4 A I don't know. 5 Q Did you attend either of these meetings? 6 A I remember attending the August 7th meeting. 7 Q What was discussed at that meeting? 8 A The context of the meeting I don't have any 9 specific details. 10 Q How about generally? 11 A I remember one investigator arriving late and I 12 remember being in charge of administrating, 13 like making sure the food got there on time and 14 the drinks got there on time and the 15 participants' name tags were all there, but as 16 far as discussion, I have really no 17 recollection. 18 Q Did you sit in on the meeting? 19 A Probably most of the time. 20 Q Do you know if they talked about the protocol 21 in general? 22 A As I said, I really don't remember what was 23 talked about. 24 Q Does this exhibit refresh your recollection as Page 148 1 to any of the people who attended that meeting? 2 A No, outside of the one error. 3 Q Okay. When you say error, you mean 4 Dr. Markovitz's name is not effaced from -- 5 A Yes. 6 Q Who is Dr. Markovitz? 7 A I think he's an investigator from Ohio. 8 Q Do you know if any of the people that attended 9 the meeting on August 7th, 1991 were approached 10 to be clinical investigators on B1Y MC HCFQ, 11 the rechallenge protocol? 12 A I really don't know if the investigators were 13 chosen. 14 Q Were any changes to the protocol made as a 15 result of this meeting? 16 A I don't remember. 17 (Deposition Exhibit 19 was marked for 18 identification.) 19 Q Is it customary for physicians to sign 1572s 20 and provide their C.V. if they are not going to 21 participate in a clinical trial? 22 MR. MYERS: If they are not? 23 MS. ZETTLER: If they are not going 24 to participate in a clinical trial. Page 149 1 A It's not standard practice. 2 Q In Exhibit 19 the person Clarence Boudreau is 3 writing to you; correct? 4 A Yes. 5 Q Who is Clarence Boudreau? 6 A He's a CRC in Canada. 7 Q And he says that Dr. (Blank) is very interested 8 in participating in the rechallenge protocol; 9 correct? 10 A Yes. 11 Q And he enclosed signed 1572s, 1572 Supplement, 12 PIR and C.V.; correct? 13 A Yes. 14 Q Does this indicate to you that this doctor was 15 signing up to be a clinical investigator on the 16 rechallenge protocol? 17 A Yes. 18 Q What's a PIR? 19 A I don't know. 20 Q What's a 1572 Supplement? 21 A It's Page 2 (indicating). 22 Q Of the exhibit? 23 A Of the exhibit. 24 Q It says dated June 17th, 1991; correct? Page 150 1 A Yes. 2 Q And the letter's confirming the meeting on 3 August 7th, 1991 or dated July 31st, 1991; 4 correct? 5 A Excuse me? 6 Q Exhibit No. 18, the letters that comprise 7 Exhibit 18 are generally dated July 31st, 1991; 8 correct? 9 A Yes. 10 Q Does this refresh your recollection as to 11 whether or not the people who attended the 12 meeting on August 7, 1991 were to be clinical 13 investigators on the rechallenge study? 14 A No. 15 Q Do you recall a clinical investigator from 16 Canada being signed up to participate in the 17 rechallenge study? 18 A I recall that Clarence had an investigator that 19 was interested in becoming an investigator but 20 also was perhaps included in our consultant 21 board, and sometimes the clinical 22 investigator -- the CRCs jump the gun and send 23 in all of their paperwork. 24 Q Who is James A. Hafner? Page 151 1 A He's a CRC or formerly was a CRC. 2 (Deposition Exhibit 20 was marked for 3 identification.) 4 Q Are you familiar with this letter? 5 A No. 6 Q On the second page it says at the top "I am 7 enclosing a copy of our latest brochure 8 describing Hill (blank)." What is "Hill", if 9 you know? 10 A Don't know. 11 Q There are several pages attached to that 12 letter, one of which was actually produced in 13 the middle of the letter. If you'll notice in 14 the bottom right-hand corner it says 15 Pz2445 486, 488 and then 487, okay? 16 A Yes. 17 Q Is that your handwriting on that 18 Page 487? 19 A I don't think so. 20 Q On the last page at the top is a name. It 21 looks like Roberta and the last name is hard to 22 read, but it says -- I believe -- either D-a or 23 D-o-r-j-a-y. Does that look familiar to you? 24 A Yes. Page 152 1 Q Can you tell me who that is. 2 A It's an investigator. 3 Q And could you spell that? Is that your 4 handwriting, that last page? 5 A The upper right-hand corner looks like my 6 signature and maybe some scribblings of a phone 7 number, but I don't think the rest -- it 8 doesn't seem like it's my handwriting on the 9 rest of the page. 10 Q Could you pronounce that last name, that 11 investigator's last name for me if you know? 12 MR. MYERS: Go ahead if you can. 13 A Dominguez. 14 Q Dominguez, okay. Underneath that it says "very 15 difficult". Do you know what that means? 16 A No. 17 Q Is Dr. -- is this person, is this Roberta? 18 A Roberto. 19 Q Roberto, okay. Is this a Lilly employee? 20 A No. 21 Q Is this an investigator that was considered for 22 the rechallenge protocol? 23 A I don't remember if any investigators were 24 chosen. Page 153 1 Q Is this person, was Dr. Dominguez a participant 2 in the August 7th, 1991 meeting to discuss the 3 protocol? 4 A I don't remember. 5 Q Dr. Markovitz, you said you thought he was from 6 Ohio. Was he from Cleveland? 7 A He could have been. 8 (Deposition Exhibit 21 was marked for 9 identification.) 10 Q Does Exhibit 21 refresh your recollection as to 11 whether or not people were approached to 12 participate as investigators in the rechallenge 13 protocol? 14 A Once again I believe that specific 15 investigators were not identified. 16 Q Well, this person seems to think that they're 17 going to be an investigator, don't they? 18 A A lot of people think they're going to be 19 investigators. 20 Q Is this Dr. Markovitz? 21 A I believe it could be and that's only based on 22 what I understand his specialty is and the 23 context of the letter. 24 Q What's his specialty? Page 154 1 A I know he works with some Axis I and II 2 instruments. 3 Q Are you familiar with any of the authors of the 4 papers that are attached to the letter in 5 Exhibit 21? 6 A Page 484, Dr. Kalin in the middle had been an 7 investigator in some earlier Fluoxetine 8 studies, I believe. 9 Q Was Dr. Kalin involved at all in the 10 rechallenge protocol or the study? 11 A I don't remember. It's the only name I 12 recognize. 13 Q Were the suggestions of the participants in the 14 August 7th meeting taken into consideration 15 when developing the protocol, the rechallenge 16 study? 17 A I don't -- I don't remember. 18 (Deposition Exhibit 22 was marked for 19 identification and a discussion was held 20 off the record.) 21 Q Do you recognize Exhibit 22? 22 A No. 23 Q This person seems to think that they're going 24 to be an investigator on the rechallenge Page 155 1 protocol, too, don't they? 2 A Yes. 3 Q Does this refresh your recollection as to 4 whether or not investigators were in fact 5 recruited to participate in the rechallenge 6 study? 7 A No. 8 Q Who else from Lilly was at the August 7th, 1991 9 meeting regarding the rechallenge protocol? 10 A Charles Beasley. 11 Q Anybody else? 12 A Probably Ken Fluharty. 13 Q Who is Ken Fluharty? 14 A He was a local CRC that would work on the 15 budget concerns with me. 16 Q Anybody else? 17 A There may have been somebody from statistics 18 there. 19 Q How about Dr. Kotsanos, was he there? 20 A I don't think so. 21 Q Anybody from systems? 22 A I don't think so. 23 Q Any other clinical research physicians from 24 Lilly? Page 156 1 A I don't think so. 2 Q Was Dan Russell there? 3 A I don't think so. 4 Q At the bottom of the first page of Exhibit 22 5 this person states "I have also had the 6 opportunity to review a draft of the protocol 7 entitled In-depth Assessment of Patients with 8 Psychobehavioral Deterioration while on 9 Antidepressants." Is that the third study that 10 you worked on? 11 A The only clue I have that it probably is is the 12 word deterioration. 13 Q How about study B1Y MC SOO1? 14 A I knew it was an S number but -- 15 Q Does that sound familiar? 16 A I know that there is an S number protocol that 17 went along with Miller's but -- 18 Q Do you know if that study was performed? 19 A To my knowledge, no. 20 Q Why not? 21 A I have no idea. 22 Q Did you work on that protocol? 23 A I drafted that protocol. 24 Q Did you do any other work on that study? Page 157 1 A No. 2 (Deposition Exhibit 23 was marked for 3 identification.) 4 Q Does this refresh your recollection as to 5 whether or not Dr. Dunner was involved in the 6 rechallenge study? 7 A He was invited to the -- obviously to the 8 meeting. 9 Q You wrote the letter that is the first page of 10 Exhibit 23; correct? 11 A Yes. 12 Q In there you state, third line down, "This 13 protocol will be reviewed by other 14 investigators at an August 7th meeting in 15 Indianapolis. If scheduling allows, you may 16 name a co-investigator to attend the meeting in 17 your absence"; correct? 18 A Yes. 19 Q Why do you think that these guys all have the 20 idea that they were going to be investigators 21 on the protocol? 22 A Probably because I use the term investigators 23 and physicians interchangeably. 24 Q You don't think it was really because they were Page 158 1 really meant to be investigators on the 2 protocol? 3 A No, I don't believe so. 4 Q Did you find yourself in the embarrassing 5 situation that you had to call these people up 6 and tell them that they weren't in fact being 7 invited to be investigators on the protocol? 8 A No, I did not. 9 Q Did anybody call these people up and tell them 10 they weren't going to be investigators on the 11 protocol? 12 MR. MYERS: When you say "these 13 people", who are we talking about? 14 Q All the people we've just discussed in the past 15 half an hour or so that had indicated that they 16 thought they were going to be investigators on 17 the protocol and by the letters that were 18 written to either you or Dr. Beasley. 19 A I did not call them. I don't know if anybody 20 else in my area did. 21 Q Did Dr. Beasley review this letter before you 22 sent it out? 23 A Probably not. 24 Q It's still your testimony that to the best of Page 159 1 your knowledge nobody was ever intended to be a 2 clinical investigator on any of these trials? 3 A Correct. 4 MR. MYERS: When you say "these 5 trials", you mean the rechallenge protocol? 6 MS. ZETTLER: Yes. 7 MR. MYERS: She's already told you 8 about the Miller thing. 9 MS. ZETTLER: Right. 10 Q To your knowledge was any of Dr. Dunner's 11 suggestions in the letter addressed to Charles 12 Beasley on August 2nd, 1991 included in the 13 protocol? 14 A I don't know that. 15 Q To your knowledge was it ever the intention of 16 Eli Lilly to audio tape the suicide ratings 17 conducted as a part of the rechallenge study as 18 suggested by Dr. Dunner in the first page of 19 his letter? 20 A There was some mention in discussions that I 21 recall, not of audio taping but of videotaping 22 for teaching purposes. 23 Q And these would be videotapes of actual suicide 24 ratings? Page 160 1 A Yes. 2 Q Done on actual patients? 3 A Yes. 4 Q Participating in an actual study? 5 A Yes. 6 Q Were those ever done? 7 A Not to my knowledge. 8 Q Other than blood and urine work, were there any 9 other physiological-type tests that were to be 10 done on the patients included in the 11 rechallenge study such as spinal taps and 12 things of that nature? 13 A I don't remember. 14 (Deposition Exhibit 24 was marked for 15 identification.) 16 Q Do you recall this letter? 17 A Excuse me? 18 Q Do you recall this letter, Exhibit 24? 19 A Now that I see it. 20 Q And what's the purpose of sending out all these 21 scales to a "Dr. Somebody" since we don't know 22 who it is since it's blacked out? 23 A Somebody probably was not familiar with all the 24 scales and asked for copies of them. Page 161 1 Q Was this before the meeting on August 7th? 2 A Yes. 3 Q Would this have been somebody who was attending 4 the meeting on August 7th or at least have been 5 invited to attend? 6 A Perhaps. 7 Q Who else would you have sent this to? 8 A Somebody who knew that I had a large collection 9 of rating scales. 10 Q You mention upcoming protocols though in the 11 letter, don't you? 12 A Yes. 13 Q Would you mention upcoming protocols if the 14 person that you were writing to was not 15 involved in those protocols either as a 16 consultant or a potential clinical 17 investigator? 18 A Probably not. 19 Q Is Mario Savelloni the kind of CRC that would 20 jump the gun and sign up investigators prior to 21 being given the go-ahead to do so? 22 A Yes. 23 Q Did he do that a lot? 24 A Yes. Page 162 1 Q Was he ever called on the carpet for it? 2 A No. 3 Q Why not? 4 A A lot of times the first person to get their 5 paperwork in gets the study. 6 Q When you say a lot of times the person who is 7 first to get their paperwork done gets the 8 study, do you mean the CRC or the clinical 9 investigator? 10 A The investigator. 11 Q Do you know if Dr. Beck was ever included in 12 either consulting regarding the rechallenge 13 protocol or actual participation in the study? 14 A No, not to my knowledge. 15 Q Dr. Beck's Lethality Scale? 16 A Yes. 17 Q Have you ever spoken with Dr. Beck? 18 A Yes, I think I did. 19 Q In regards to the rechallenge? 20 A I don't remember in what context I spoke to 21 Dr. Beck. 22 Q Well, did you speak to him regarding 23 participating in clinical trials other than the 24 rechallenge or the suicide rating scale Page 163 1 validation studies? 2 A No, I spoke to Dr. Beck to find out who held 3 the copyright to his scales. 4 Q Did either you or anybody else from Lilly ever 5 approach Dr. Beck about developing a scale to 6 be used on the rechallenge protocol? 7 A Not to my knowledge. 8 Q Did you get permission from Dr. Beck or whoever 9 owned the copyright on Dr. Beck's scales to use 10 his scales on either of these studies, the 11 rechallenge or suicidality rating scale study? 12 A Yes. 13 Q Which study? 14 A It was used in the MSSI-R study. 15 (Deposition Exhibits 25 and 26 were 16 marked for identification.) 17 Q Have you had a chance to look at Exhibit 25? 18 A Yes. 19 Q Is this letter from Dr. Beck? 20 A I don't believe so. 21 Q Have you ever heard of a Dr. Haas, H-a-a-s? 22 A No. 23 Q Do you know who this letter is from? 24 A No, I don't. Page 164 1 Q Before you look at that, did you ever talk to 2 Dr. Beasley about the CRCs approaching 3 potential clinical investigators for the 4 rechallenge protocol? 5 A No. 6 Q Does this refresh your recollection as to 7 whether or not people were recruited to be 8 clinical investigators on the rechallenge 9 protocol? 10 A No, it does not. 11 Q Look at letter (c) on the first page. This is 12 a memo from Mario Savelloni; right? 13 A Yes. 14 Q And you're included on the recipient list, 15 aren't you? 16 A Yes. 17 Q Along with Dr. Beasley? 18 A Yes. 19 Q Okay. About a third of the way down, 20 Paragraph (b), it says "As instructed by 21 Charles Beasley, I will determine if 22 Dr. (Blank) wishes to be the lead investigator 23 and also if he has certain physicians that he 24 prefers"; correct? Page 165 1 A Yes. 2 Q Does that indicate to you that Dr. Beasley 3 wanted people approached to see if they would 4 participate as investigators in the rechallenge 5 study? 6 A If you read this letter, yes. 7 Q If Dr. Beasley read this letter? I don't 8 understand what you just said. 9 A In reading this letter, yes, you would assume 10 that Charles had instructed people. 11 Q And it's your testimony that he did not do so 12 or that you don't know? 13 A I don't know. 14 Q Is it common practice for the CRA to be kept 15 out of the loop when people are being recruited 16 as clinical investigators? 17 MR. MYERS: I'll object to the 18 form. Number one it's argumentative, and 19 number two she told you she didn't know if 20 people were being recruited or not. She's told 21 you that half a dozen times. 22 Q I'm asking right now if it's common practice at 23 Lilly for the CRC to be kept out of the loop 24 when people are being recruited as clinical Page 166 1 investigators? 2 MR. MYERS: And thus I object to 3 the form because you're assuming they were 4 being recruited. 5 Q Go ahead and answer if you can. 6 A All I can say and reiterate is that CRC's jobs 7 are to constantly recruit investigators. 8 Q Regardless of whether or not there is a study 9 to recruit them for? 10 A Yes. 11 Q But this letter or this memo is specific to the 12 rechallenge and the deterioration protocols; 13 isn't it? 14 A Yes. 15 Q As well as Dr. Miller's suicide validation 16 scale? 17 A Yes. 18 Q Suicide scale validation study, I should say. 19 To your knowledge was anybody at McLean 20 Hospital approached to participate either as a 21 consultant on the rechallenge protocol or 22 participating as a clinical investigator? 23 A I don't remember. 24 Q Have you ever heard of DEN II? Page 167 1 A Yes. 2 Q What is DEN II? 3 A It's an update to the DEN system. 4 Q In what way was the DEN system updated to 5 become DEN II? 6 A There were system enhancements made to my 7 knowledge. 8 Q What system enhancements? 9 A I don't know what system enhancements. 10 Q Do you know why the system was enhanced? Was 11 it in response to something, a problem? 12 A No. Software is constantly being updated. 13 Q How many times was the DEN updated or enhanced 14 when you worked as a CRC in medical? 15 A To clarify I was a CRA. 16 Q I am sorry, CRA. You're right. 17 A As far as I understand, there was DEN and there 18 was DEN II. 19 Q Are you familiar with the situation where 20 Medical Quality Assurance reviewed the DEN 21 system? 22 A No. 23 Q Why did Dan Russell turn over his 24 responsibilities as CRA on the rechallenge and Page 168 1 validation studies to you? 2 A Because he was probably directed to do so. 3 Q Do you know why he was directed to do so? 4 A Maybe he was busy. I don't -- I don't know. 5 Q Have you ever heard of a source book? 6 A No. 7 (Deposition Exhibit 27 was marked for 8 identification.) 9 Q Have you had a chance to review Exhibit 27? 10 A Yes. 11 Q Is this your handwriting? 12 A Up through the last page, yes. 13 MS. ZETTLER: Okay. Why don't we 14 take about a 15-minute break. I think we're 15 almost done. 16 MR. MYERS: Okay. 17 (A brief recess was taken.) 18 Q Have you looked at Exhibit 27? 19 MR. MYERS: Yes. 20 MS. ZETTLER: Okay. Well, not you, 21 Larry. I'm talking to the witness. 22 MR. MYERS: And she said they were 23 all her writing except the last page; is that 24 right? Page 169 1 THE WITNESS: Yes. 2 Q Can you tell me what that exhibit is, at least 3 the pages that are in your handwriting? 4 A Collect notes regarding the rechallenge 5 protocol. 6 Q Is this all one set of notes or is it various 7 notes? 8 A I don't know. 9 Q On the first page it says questions from -- it 10 looks like SCRFC. 11 A Yes. 12 Q What is SCRFC? 13 A Standard Case Report Form Committee. 14 Q And that was a committee that you were on? 15 A No, that was -- I had been on that at one time. 16 I was not during this time. I present -- I had 17 to perhaps present the case report form ideas 18 and the rechallenge protocol. 19 Q So you helped develop the case report forms for 20 the rechallenge protocol? 21 A Yes. 22 (Deposition Exhibit 28 was marked for 23 identification.) 24 Q Is the case report form attached to Exhibit 28 Page 170 1 the case report form for HCFQ of the 2 rechallenge protocol? 3 A No. Only the MSSI-R is. 4 Q What other things were included in the case 5 report form for HCFQ? 6 A Probably -- I'd have to go by my notes, the 7 notes on 27. 8 Q What do you get from your notes on 27 with 9 regards to what was contained in the 10 rechallenge protocol CRFs? 11 A Not much. That we probably included SCID and 12 SCID II and CGI. 13 Q Is it common practice at Lilly to attach a copy 14 of the clinical report form to the protocol? 15 A No. 16 Q If the study was started or investigators were 17 being recruited, would they be provided a copy 18 of the proposed clinical report form along with 19 the protocol? 20 A No. 21 Q When would the clinical investigators see the 22 clinical report form? 23 A At the start-up meeting. 24 Q To your knowledge was there ever a draft of the Page 171 1 clinical report form that was going to be used 2 for the rechallenge study made? 3 A Based on Exhibit 27, I would have to say, yes, 4 there was a draft because I had to approach the 5 Standard Case Report Form Committee with 6 something. 7 Q Were you involved in drafting the case report 8 forms? 9 A Probably. 10 Q Did you see a copy of the case report form in 11 the documents that you found for Mr. Myers that 12 were produced to me prior to today's 13 deposition? 14 A No. 15 Q If a case report form for the rechallenge 16 protocol was developed, would you have had a 17 copy of that in your file on the rechallenge 18 study? 19 A Maybe. 20 Q And if there was one in your file, it would 21 have been turned over to legal at Lilly? 22 A Yes. 23 Q If you look at the third page of Exhibit 27, 24 can you tell me what these notes are regarding? Page 172 1 A They look like notes about the protocol or 2 questions that came up about the protocol. 3 Q On the left-hand side there is a note that says 4 "with regard to obsessionalities". 5 A Yes. 6 Q Were people suffering from obsessive compulsive 7 disorder to be included in this trial? 8 A I don't know. I'd have to look in the 9 inclusion/exclusion criteria. 10 Q Go ahead. 11 A It doesn't look like they were specifically 12 included or excluded. 13 Q At the top of Page 208 on Exhibit 27 it says in 14 a box "CMI excluded. Except in combo of either 15 Mapro, TCA or Fluoxetine? 16 A Yes. 17 Q What is CMI? 18 A CMI is clomipramine. 19 Q Why was clomipramine excluded except in those 20 specific cases? 21 A Probably because clomipramine was not an 22 approved drug in the United States. 23 Q Is that a Lilly drug? 24 A No, it is not. Page 173 1 Q Why would it be used in combination with a 2 Mapro, TCA or Fluoxetine? 3 A Because people practice polypharmacy. 4 Q When you say "people practice polypharmacy", 5 what do you mean? 6 A Polypharmacy means taking multiple drugs at one 7 time. 8 Q Who would be the people who are practicing 9 that, the patients or the doctors? 10 A The doctors. 11 Q So why would it be okay to use clomipramine in 12 combination with those other drugs even though 13 it's not approved here in the United States but 14 it wouldn't be permissive to use it in and of 15 itself for that reason? 16 MR. MYERS: Before she answers, I 17 think that probably calls at least in part for 18 some sort of a medical judgment. I object to 19 the form on that basis. If you know as a 20 layperson, tell her. 21 A I don't know. 22 Q Then underneath that, it says "How will this 23 effect Canada?" What do you mean by that? 24 A Clomipramine is an approved drug in Canada. Page 174 1 Q At this time you knew that there were going to 2 be trials -- at least part of the rechallenge 3 study was going to be done in Canada? 4 A If it was done in Canada. 5 Q Two pages back on Page 210 at the bottom it 6 says "CMB to look at effect". CMB is Charles 7 Beasley, I take it? 8 A Yes. 9 Q "CMB to look at effect of HCFQ" -- what does 10 that Delta sign stand for? 11 A Changes. 12 Q -- "to S001", what do you mean by that? 13 A I don't know. 14 Q S001 was supposed to be run in conjunction with 15 Dr. Miller's study, wasn't it? 16 A Not that I'm aware of. 17 Q I thought you testified earlier that it was 18 supposed to be run in conjunction or at the 19 same time as Dr. Miller's study. 20 A No. 21 MR. MYERS: I don't remember that. 22 THE WITNESS: I don't remember that 23 either. 24 MS. ZETTLER: Okay. Page 175 1 Q And to your knowledge S001 was never run; 2 correct? 3 A To my knowledge S001 was never run. 4 Q Did Lilly anticipate performing S001 before the 5 rechallenge protocol? 6 A I don't know. 7 Q Was S001 a surveillance study developed in 8 anticipation of the rechallenge protocol? 9 A I don't remember. 10 Q A couple pages back from there on Page 212 11 appears to be meeting notes; is that correct? 12 A Just looks like notes on the protocol to me. 13 Q Well, if you keep going back a couple pages, 14 take a look at the next four or five pages if 15 you would. 16 A Okay. 17 Q Do these appear to be meeting minutes or notes? 18 A It's hard to say what they were. 19 Q Can you tell me what has been marked out on 20 those pages? 21 A No. 22 Q Are they people's names? 23 A I don't know. 24 Q At the top of Page 212 it says "(Blank) who has Page 176 1 seen Teicher phenomenon Amsterdam". 2 A Yes. 3 Q Are you familiar with a doctor in Amsterdam who 4 has witnessed Dr. Teicher's phenomenon in 5 patients on Fluoxetine? 6 A I'm familiar with Dr. Amsterdam. I can't say 7 what kind of patients he's seen. 8 Q So Amsterdam is a doctor and not a place? 9 A Yes. 10 MR. MYERS: Maybe both. 11 MS. ZETTLER: Well, not in the 12 middle of the same thing, I hope. 13 Q Where is Dr. Amsterdam located? 14 A I think Philadelphia. 15 Q Was he at the August 7th, 1991 meeting on the 16 rechallenge protocol? 17 A He may have been. 18 Q So is he a clinical investigator for Lilly on 19 Fluoxetine outside the protocol, rechallenge 20 protocol? 21 A He had been an investigator. 22 Q On depression trials? 23 A I don't remember. 24 Q What's Dr. Amsterdam's first name if you know? Page 177 1 A Jay. 2 Q Did you take notes during the August 7th, 1991 3 meeting? 4 A I don't remember. 5 Q Look at Page 213, please, the middle of the 6 page, the paragraph that starts "CMB will 7 liberalize. Perhaps two out of three of 8 inclusion b. Let's make the rules ourselves 9 (Blank). Ask patient how it was serious or 10 fleeting." 11 A Yes. 12 Q Does that indicate to you that that's a 13 suggestion by somebody? 14 A No. 15 Q Could you turn to Page 215, please. 16 A (Witness complies). 17 Q Again towards the middle of the page it says 18 "San Diego wants taped (sic) or tapped". Do 19 you see that? 20 A Yeah. 21 Q What do you mean by that? 22 A I don't know. 23 Q Have you ever heard of a HAM-A? 24 A Yes. Page 178 1 Q What's a HAM-A? 2 A Hamilton Anxiety Scale. 3 Q Was that used in the rechallenge protocol? 4 A I don't know. I'd have to look. Not according 5 to the version that I have. 6 Q Not according to Exhibit 28? 7 A Yes. 8 Q To your knowledge is Exhibit 28 the final draft 9 of HCFQ? 10 A I don't know. 11 Q On the last page of Exhibit 27 do you recognize 12 that handwriting? 13 A That's Charles Beasley's. 14 Q Have you had occasion to see Dr. Beasley's 15 handwriting often? 16 A Yes. 17 Q Can you go back to Exhibit 28 again for a 18 second. If you look towards the back at the 19 MSSI -- 20 MR. MYERS: What page? 21 MS. ZETTLER: 305, Appendix E. 22 Q Up top in the left-hand corner it says 23 "Clinical Report Form, Fluoxetine vs. Placebo 24 in MDD, B1Y MC HCFP". Page 179 1 A Yes. 2 Q Does this refresh your recollection as to what 3 study HCFP was? 4 A No. 5 Q To your knowledge was HCFP related in any way 6 to the rechallenge or the validation of 7 Dr. Miller's scale? 8 A Not to my knowledge. 9 Q Was it related to the deterioration study, 10 Study S001? 11 A Not to my knowledge. 12 Q Besides Study S001, Study S002 and the 13 rechallenge protocol HCFQ, were there any other 14 studies considered, developed, performed or 15 otherwise by Lilly related in any way to 16 suicidality? 17 A I don't know. 18 Q Were there any studies related or performed by 19 Lilly considered, developed or otherwise 20 related in any manner to homicidality or 21 hostility? 22 A I don't know. 23 Q How about anxiety? 24 A I think there were anxiety trials. Page 180 1 Q Anxiety trials for the treatment of anxiety? 2 Or, I'm sorry, strike that. Trials for the 3 treatment of anxiety or trials for the study of 4 anxiety and the use of Fluoxetine? 5 A I don't know. 6 Q How about violent aggressive behavior? 7 A I don't know. 8 Q Have you ever worked with Patricia Williams? 9 A No, I don't think so. 10 Q Do you know, have you heard of Patricia 11 Williams? 12 A No. 13 Q How about Dr. Wheadon, have you ever worked 14 with him directly? 15 A Yes. 16 Q In what capacity? 17 A He was the research physician when I worked on 18 another indication. 19 Q Is Dr. Wheadon still with Lilly? 20 A No. 21 Q When did he leave Lilly? 22 A More than a year ago. 23 Q Do you know where he is now? 24 A No. I know where he went then, but I don't Page 181 1 know where he is now. 2 Q Where did he go a year ago? 3 A More than a year ago I know he went to 4 Smith-Kline. 5 Q Do you know why he left Lilly? 6 A No. 7 Q Do you know if he was asked to leave or if he 8 left on his own accord? 9 A I don't know. 10 Q Have you ever heard of a Dr. Dorothy Dobbs? 11 A Yes. 12 Q Did you ever work with Dr. Dobbs? 13 A No. 14 Q How do you know of Dr. Dobbs? 15 A I've read that name in files. 16 Q To your knowledge did Dr. Dobbs work on 17 Fluoxetine at Eli Lilly? 18 A I think that she did. 19 Q Do you know what capacity she worked on 20 Fluoxetine? 21 A No. 22 Q Do you know if Dr. Dobbs is still with Eli 23 Lilly? 24 A No, I don't. Page 182 1 (Deposition Exhibit 29 was marked for 2 identification.) 3 Q Do you recognize Exhibit No. 29? 4 A No. 5 Q Do you recognize the handwriting on the first 6 page of Exhibit 29? 7 A No. 8 Q Have you ever seen this document before? 9 A I'm copied on it. I'm sure I have seen it, but 10 I don't have any specific recollection to it. 11 Q The title of the second page is "To Discuss 12 Psychobehavioral Deterioration and its 13 Meaning"; correct? 14 A Yes. 15 Q Is this to your knowledge related to 16 Study S001? 17 A I would assume so. 18 Q Do you recall attending such a meeting? 19 A No. 20 Q Do you recall attending any meetings on 21 Study S001? 22 A Not specific meetings. Maybe I met with 23 Dr. Beasley or I met with somebody. 24 Q Have you worked with Gary Tollefson? Page 183 1 A Yes. 2 Q Did you work with Dr. Tollefson on the 3 rechallenge protocol? 4 A Dr. Tollefson is the director. 5 Q Of what? 6 A Of the department that was responsible for the 7 rechallenge protocol. 8 Q Okay. So I guess that means your answer is, 9 yes, you worked with him? 10 A Yes. 11 Q In what capacity did you work with 12 Dr. Tollefson? 13 A He was the director of the physicians that were 14 responsible, so he had the ultimate say usually 15 in what went on. 16 Q Is it your understanding that Dr. Tollefson 17 prior to coming to Lilly was a clinical 18 investigator for Lilly on Fluoxetine? 19 A Yes. 20 Q How long has Dr. Tollefson been with Lilly as 21 an employee? 22 A A few years. 23 Q Do you know how long it was that he came on 24 board before the protocol for the rechallenge Page 184 1 study was written? 2 A No. 3 Q Do you recall a time at Lilly where either the 4 suicidality scale or Studies S001 or S002 were 5 going to be completed on a retrospective basis? 6 MR. MYERS: I object to the form. 7 I don't understand when you say on a 8 retrospective basis. 9 Q Well, in the first full paragraph of the text 10 under Gary it says "The retrospective study is 11 flawed. Not possible to fill out these scales 12 retrospectively." I'm trying to figure out 13 what is meant by that. 14 MR. MYERS: That's a different 15 question than the one you asked. 16 MS. ZETTLER: Okay. 17 MR. MYERS: So which is the 18 question? 19 MS. ZETTLER: The one I just asked. 20 MR. MYERS: What does this mean 21 here? 22 MS. ZETTLER: If she knows. 23 A Only what it says in front of me now. 24 Q What do you glean from what you're reading in Page 185 1 front of you? 2 A That perhaps there was some thought to going 3 back and collecting data retrospectively. 4 Q To fill out other scales? 5 A Yes. 6 (Deposition Exhibit 30 was marked for 7 identification.) 8 Q Do you recognize the mail messages that 9 comprise Exhibit 30? 10 A Yes. 11 Q The first one is dated June 13th, 1991 and it's 12 entitled "DEN Suicidality Data for Leigh". 13 A Yes. 14 Q Does this refresh your recollection as to what 15 a source book is? 16 A Vaguely. 17 Q What do you mean? What's your interpretation 18 of a source book? 19 A At the time I think we were keeping a binder 20 that had all the information that we were 21 providing people such as copies of slides, 22 et cetera, so we could provide them to other 23 people as well. And it happened to be located 24 in my office. Page 186 1 Q The rest of the message says "Bob Hunt has 2 provided the DEN suicidality data for WLT this 3 morning and we both took it over to Leigh's 4 office." Were you involved in that? 5 A I don't believe so. 6 Q Okay. The last sentence of that paragraph says 7 "We are planning on having the data on all 8 serious events and violent events by tomorrow 9 afternoon." Do you recall a collection or 10 analysis or both of violent events? 11 A I believe violence was addressed in the U.S. 12 supplement to the NDA. 13 Q Did you have any responsibilities with either 14 collecting that information or analyzing it? 15 A No. 16 Q Were you ever charged in reviewing clinical 17 report forms or any other documents to collect 18 violent events as you did with the suicidality 19 events we talked about earlier? 20 A Not specifically, no. 21 Q How about generally? 22 A Maybe perhaps in the earlier testimony that I 23 reviewed case report forms. The why and the 24 specifics of what that data was used for I'm Page 187 1 not for certain. 2 Q A couple pages back, Page 66. What is white 3 paper? 4 A A list of facts. I think it's an FDA term. 5 Q Is it a paper that's submitted to the FDA by 6 Lilly? 7 A I don't know. 8 Q And when it says at the bottom of the paragraph 9 that "a copy has been supplied to Catherine for 10 the file", is that the file you were just 11 talking about? 12 A Yes. 13 Q So if you were given a copy of that, it would 14 have been placed in the source book or file? 15 A Yes. 16 Q Would you look at Page 167. It's the last page 17 actually of the exhibit. 18 A (Witness complies). 19 Q Do you recognize that E-mail? 20 A Vaguely. 21 Q What is the International Data Collection - 22 Phase II? 23 A My thoughts are this was to collect -- based on 24 this, not the -- do the same analysis on Page 188 1 non-depression clinical trials. 2 Q When you say the same analysis, you mean 3 collect data from the non-depression clinical 4 trials as you did with the depression clinical 5 trials from outside the U.S.? 6 A Yes. 7 Q To your knowledge was this ever done? 8 A No. 9 Q Why not? 10 A I don't know. 11 Q To your knowledge was a search ever made of the 12 DEN database for serious adverse events 13 occurring in non-depression O.U.S. clinical 14 trials? 15 A I don't know. 16 Q How about U.S. non-depression clinical trials? 17 A I don't know. 18 Q Were you ever involved in Prozac strategy 19 meetings? 20 A Yes. 21 Q How often? 22 A Limited. 23 Q Pardon? 24 A Limited, very limited. Page 189 1 Q Can you give me an idea of how many? 2 A Maybe less than ten times. 3 Q What is a Prozac strategy meeting? 4 A When I attended, it was to discuss the O.U.S. 5 data and how we would respond and how could we 6 possibly collect that and what our strategy 7 behind doing that was. 8 Q What was the strategy behind collecting the 9 O.U.S. data? 10 A That work sheets would be developed and we 11 would assemble a task force and we would go to 12 Europe and everything else that's been 13 described over the -- earlier in my testimony. 14 Q To your knowledge what's the reason for doing 15 all of that? What was the reason for 16 collecting all the O.U.S. depression data? 17 A To be able to submit some additional 18 information to the FDA in an organized fashion. 19 Q The FDA requires that all the O.U.S. 20 international trials be reported on as they 21 were conducted and completed; correct? 22 A No. 23 Q The O.U.S. trials did not have to be reported 24 to the FDA? Page 190 1 A Not unless they were performed under the 2 U.S. IND. In general, you have to report under 3 U.S. IND regulations. Annually you have to 4 report (quote) most -- a table listing the most 5 frequent adverse events and also some basic 6 information. There is not specific ground 7 rules or criteria. 8 Q But the data was collected from the O.U.S. 9 trials when you were involved in the project 10 primarily to provide safety information to the 11 FDA; correct? 12 A Yes. 13 Q All serious adverse events that occurred in the 14 international or the outside the U.S. clinical 15 trials had already been reported to the FDA? 16 A Yes. 17 Q Just not as organized as you did it the second 18 time, huh? 19 A Excuse me? 20 Q Just not as organized as you did it the second 21 time after you went over to Europe and got all 22 the information; right? 23 A No. A different mechanism. 24 MS. ZETTLER: Okay. That's all Page 191 1 I've got. 2 MR. MYERS: Any questions down on 3 the end? 4 MS. WILKINS: Off the record. 5 (A discussion was held off the record.) 6 MS. WILKINS: No questions. 7 AND FURTHER THE DEPONENT SAITH NOT. 8 9 --------------------------- 10 CATHERINE H. MESNER Page 192 1 STATE OF INDIANA ) ) SS: 2 COUNTY OF MARION ) 3 I, Linda M. Bour, a Notary Public in and 4 for the County of Marion, State of Indiana at 5 large, do hereby certify that CATHERINE 6 H. MESNER, the deponent herein, was by me first 7 duly sworn to tell the truth, the whole truth, 8 and nothing but the truth in the aforementioned 9 matter; 10 That VOLUME II of the foregoing 11 deposition was taken at the offices of Baker & 12 Daniels, 300 North Meridian Street, Suite 2700, 13 Indianapolis, Marion County, Indiana, on the 14 15th day of October 1993, commencing at the 15 hour of 10:15 a.m., in accordance with the 16 Rules of Civil Procedure; 17 That said deposition was taken down in 18 stenograph notes and afterwards reduced to 19 typewriting under my direction, and that the 20 typewritten transcript is a true record of the 21 testimony given by said deponent; and 22 thereafter presented to said deponent for her 23 signature; 24 That the parties were represented by Page 193 1 their aforementioned counsel. 2 I do further certify that I am a 3 disinterested person in this cause of action; 4 that I am not a relative or attorney of either 5 party, or otherwise interested in the event of 6 this action, and am not in the employ of the 7 attorneys for either party. 8 IN WITNESS WHEREOF, I have hereunto set 9 my hand and affixed my notarial seal this _____ 10 day of ___________, 1993. 11 12 ___________________________ N O T A R Y P U B L I C 13 My Commission Expires: 14 June 19, 1996 15 County of Residence: Marion 16 17 Page 194