1 NO. 90-CI-6033 JEFFERSON CIRCUIT COURT DIVISION ONE (1) 2 3 JOYCE FENTRESS, ET AL. PLAINTIFFS 4 5 VS. DEPOSITION FOR PLAINTIFFS 6 7 SHEA COMMUNICATIONS, ET AL. DEFENDANTS 8 * * * * * * * * * * 9 10 DEPONENT: JAMES KOTSANOS, M.D. 11 DATE: OCTOBER 21, 1993 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 Page 1 1 * * * * * * * * * * 2 3 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 4 INDIANAPOLIS DIVISION 5 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 6 Litigation ) 7 * * * * * * * * * * 8 NO. 91-02496-A 9 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 10 V. ) DALLAS COUNTY, TEXAS ) 11 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 12 * * * * * * * * * * Page 2 1 SUPERIOR COURT OF THE STATE OF CALIFORNIA 2 FOR THE COUNTY OF LOS ANGELES 3 DR. MARIUS SAINES, etc., et al., ) Case No: 4 ) SC 008331 Plaintiffs, ) 5 ) vs. ) 6 ) ELI LILLY & COMPANY, a corporation; ) 7 DISTA PRODUCTS COMPANY, a division ) of Eli Lilly & Company; and DOBS 1- ) 8 100, inclusive, ) ) 9 Defendants. ) ____________________________________) 10 11 * * * * * * * * * * Page 3 1 THE DEPOSITION OF JAMES KOTSANOS, M.D., 2 TAKEN AT THE OFFICE OF BAKER & DANIELS, 300 NORTH 3 MERIDIAN STREET, SUITE 2700, INDIANAPOLIS, 4 INDIANA 46204, ON OCTOBER 21, 1993; SAID 5 DEPOSITION TAKEN PURSUANT TO NOTICE IN ACCORDANCE 6 WITH THE RULES OF CIVIL PROCEDURE. 7 * * * * * * * * * * 8 A P P E A R A N C E S 9 10 NANCY ZETTLER COUNSEL FOR GROUP A PLAINTIFFS 11 LEONARD M. RING AND ASSOCIATES, P.C. 111 WEST WASHINGTON AVENUE, SUITE 1333 12 CHICAGO, ILLINOIS 60602 13 LAWRENCE J. MYERS COUNSEL FOR ELI LILLY AND COMPANY 14 FREEMAN & HAWKINS 4000 ONE PEACHTREE CENTER 15 303 PEACHTREE STREET, N.E. ATLANTA, GEORGIA 30308-3243 16 MARGARET M. HUFF 17 ELI LILLY AND COMPANY LILLY CORPORATE CENTER 18 INDIANAPOLIS, INDIANA 46285 Page 4 1 MIGUEL A. RUIZ 2 COUNSEL FOR DEFENDANTS CZECHOWICZ, FINK, BRUINSMA CLAUSEN MILLER GORMAN CAFFREY & WITOUS 3 10 SOUTH LASALLE CHICAGO, ILLINOIS 60603 4 PAUL SMITH 5 COUNSEL FOR PLAINTIFFS 745 CAMPBELL CENTER 2 6 8115 NORTH CENTRAL EXPRESSWAY DALLAS, TEXAS 75206 Page 5 1 I N D E X 2 3 DEPOSITION OF JAMES KOTSANOS, M.D. 4 5 DIRECT EXAMINATION BY MS. ZETTLER 7 6 CERTIFICATE 226 7 ERRATA 227 8 9 EXHIBITS 10 PLAINTIFFS' EXHIBIT NO. 4 37 PLAINTIFFS' EXHIBIT NO. 5 50 11 PLAINTIFFS' EXHIBIT NO. 6 54 PLAINTIFFS' EXHIBIT NO. 7 60 12 PLAINTIFFS' EXHIBIT NO. 8 67 PLAINTIFFS' EXHIBIT NO. 9 95 13 PLAINTIFFS' EXHIBIT NO. 10 99 PLAINTIFFS' EXHIBIT NO. 11 114 14 PLAINTIFFS' EXHIBIT NO. 12 117 PLAINTIFFS' EXHIBIT NO. 13 126 15 PLAINTIFFS' EXHIBIT NO. 14 142 PLAINTIFFS' EXHIBIT NO. 15 144 16 PLAINTIFFS' EXHIBIT NO. 16 154 PLAINTIFFS' EXHIBIT NO. 17 161 17 PLAINTIFFS' EXHIBIT NO. 18 164 PLAINTIFFS' EXHIBIT NO. 19 166 18 PLAINTIFFS' EXHIBIT NO. 20 176 PLAINTIFFS' EXHIBIT NO. 21 183 19 PLAINTIFFS' EXHIBIT NO. 22 211 PLAINTIFFS' EXHIBIT NO. 23 215 Page 6 1 COMES JAMES KOTSANOS, M.D., CALLED BY 2 THE PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, 3 WAS DEPOSED AND TESTIFIED AS FOLLOWS: 4 DIRECT EXAMINATION 5 BY MS. ZETTLER: 6 Q. Welcome back, Doctor Kotsanos. 7 A. Thank you. 8 MR. RUIZ: Nancy, before you begin, may 9 I make a statement? 10 MS. ZETTLER: Sure. 11 MR. RUIZ: For the record, I would like 12 to state once again that I'm here representing 13 Doctor Benson in Maloney versus Benson. Doctor 14 Benson is not a defendant, he is a respondent in 15 discovery and he's filed a special and limited 16 appearance, and by being here today he does not 17 waive any right to challenge the court's 18 jurisdiction. Thank you. 19 Q. (BY MS. ZETTLER) Doctor 20 Kotsanos, have you reviewed any documents between 21 your last deposition and today? 22 A. The only document I reviewed 23 was the deposition transcript. 24 Q. Do you see anything in that Page 7 1 transcript that you thought was misstated or 2 taken down wrong by the court reporter that you 3 would like to change? 4 A. Yes, we made a number of 5 changes. 6 MS. ZETTLER: I don't think I've got an 7 errata sheet. Was there anything substantive? 8 COURT REPORTER: I haven't sent it out 9 yet. 10 MS. ZETTLER: Okay. 11 Q. If you're talking just like 12 typos and names and things like that, I'm not 13 concerned with, but if you're talking about 14 something substantive. 15 A. I don't think any of it was 16 substantive, I think most of the changes were 17 typos or for clarification. 18 Q. When you say clarification, 19 what do you mean? 20 A. To make the meaning of the 21 sentence more clear or to change my uh-huh to 22 yeses. 23 Q. Okay. In making any 24 clarifications, do you recall changing the Page 8 1 substantive nature of your response, in other 2 words did you change any yeses to nos or anything -- 3 or vice versa or anything of that nature? 4 A. There was one change from a can 5 to a cannot or maybe a cannot to a can, but I 6 think that may have been a typo. 7 Q. Do you recall what the subject 8 of the question was? 9 A. I would need to see it again. 10 Q. Have you ever heard of 11 subsyndromal syndrome? 12 A. I do not know what that is, no. 13 Q. I'm sure I asked you this last 14 time, but just for speeding this up, are you a 15 psychiatrist? 16 A. No. 17 Q. Are you aware of any studies 18 that are now ongoing related to suicidality and 19 the use of Fluoxetine at Eli Lilly or on behalf 20 of Eli Lilly? 21 A. I'm unaware of any. 22 Q. How about violent aggressive 23 behavior or hostility? 24 A. I'm unaware of any. Page 9 1 Q. Are you aware of any ongoing 2 studies related to overdose and Fluoxetine being 3 performed by Lilly or on behalf of Lilly? 4 A. I'm aware of one study. 5 Q. Okay. Is that a large study? 6 A. Large is a relative term. 7 Q. Over a hundred people involved? 8 A. I do not recall if there are 9 over a hundred people in the study. 10 Q. How about a multi-center study? 11 A. Yes, I believe so. 12 Q. Is it an inpatient study or an 13 outpatient study? 14 A. I believe it's primarily 15 inpatient. 16 Q. When you say it's studying 17 overdose, do you mean the incidence of overdose 18 with Fluoxetine or the effect of Fluoxetine if 19 you overdose on it, or both? 20 A. The study to which I refer is a 21 safety study. 22 Q. Okay. So again, does that mean 23 the incidence of overdose occurring with people 24 who are taking Fluoxetine or the effect of Page 10 1 Fluoxetine if you take it in an overdose? 2 A. The latter, that is the effect 3 of Fluoxetine of taking it in an overdose. 4 Q. In other words, just to support 5 the previous findings that it's difficult to kill 6 yourself by simply overdosing on Fluoxetine 7 alone? 8 A. I believe so. 9 Q. Is it sort of like a toxicology 10 study, people are given so many milligrams of 11 Fluoxetine to see what the effect is on various 12 systems of the body? 13 A. I do not believe that's the way 14 it's set up. 15 Q. Are there comparitor drugs used 16 in the study? 17 A. I believe that the study looks 18 at patients who have overdosed on 19 antidepressants. Fluoxetine is one of the 20 antidepressants, I believe there are other 21 antidepressants, but I don't know if there are 22 any targeted antidepressants or if it's all 23 antidepressants. 24 Q. Last time we talked about a Page 11 1 couple of studies, one of them was the 2 rechallenge, another was the study I believe you 3 worked on that was to validate suicidality scale. 4 Do you remember that? 5 A. I remember our discussion, but 6 I do not believe it was on the validation of the 7 suicide scale. It was on the revision and 8 modification of an existing questionnaire. 9 Q. Is that Doctor Miller's scale? 10 A. Right. 11 Q. Do you know if the scale was 12 validated in a clinical trial performed by Doctor 13 Miller on behalf of Lilly? 14 A. I do not know if it was. 15 Q. Okay. There was a third study, 16 I believe we mentioned briefly, it was about 17 deterioration of depressed people who were taking 18 antidepressants. Do you recall that? 19 MR. MYERS: Does he recall such a study 20 or does he recall discussing it with either you 21 or Paul? 22 MS. ZETTLER: Does he recall discussing 23 it. 24 A. I don't recall us discussing Page 12 1 it. 2 Q. Do you recall such a study? 3 A. I do not recall such a study. 4 Q. Did you do any work on the 5 overdose study that's currently pending? 6 A. I have not done any work on the 7 overdose study. 8 Q. How is it that you're aware of 9 this study? 10 A. Two reasons. One, I recall 11 hearing the initial study design concept 12 presented by John Heiligenstein, and secondly, I 13 recall seeing a presentation made by John on some 14 of the preliminary findings. 15 Q. When do you recall hearing the 16 preliminary -- what did you say, the preliminary -- 17 A. Findings. 18 Q. Findings. 19 A. Maybe two weeks ago. 20 Q. What were those preliminary 21 findings? 22 A. That Fluoxetine is safe in 23 overdose as a solo overdose. 24 Q. Anything else? Page 13 1 A. There's an economic component 2 to the protocol, and there were some medical 3 resource utilization data presented as well. 4 Q. When you say economic 5 component, do you mean cost effectiveness? 6 A. No, medical resource use 7 collection. 8 Q. What do you mean by medical 9 resource use collection? 10 A. Oh, for example, number of days 11 in the intensive care unit, number of days on a 12 ventilator, that sort of information. 13 Q. Anybody die on that study? 14 A. I do not recall. 15 Q. Anybody take an intentional 16 overdose outside the parameters of the study? 17 A. I don't believe that's the way 18 the study was set up. 19 Q. How was the study set up? 20 A. I believe the study was set up 21 to look at overdoses that came into emergency 22 rooms. 23 Q. Okay. So I take it the studies 24 were done at various hospitals across the Page 14 1 country? 2 A. Right, multi-site. 3 Q. Do you recall some of the 4 hospitals where it's performed? 5 A. I do not. 6 Q. Do you recall how many sites? 7 A. I do not know. 8 Q. Explain to me a little more 9 about how the study was set up, was it a finite 10 period of time in which overdoses that came into 11 the various emergency rooms at the sites were to 12 be monitored, so to speak, and information is to 13 be gathered on these people? 14 A. I'm aware that patients who 15 presented to emergency rooms with overdoses had 16 information provided on a data collection form. 17 I do not know if there was a definite time period 18 or a targeted number of patients which was to 19 guide the end point of the study. 20 Q. You said there was preliminary 21 findings, is this study still ongoing? 22 A. I do not know if the findings 23 presented were prior to stopping the study or 24 not, I do not know that. Page 15 1 Q. Where did Doctor Heiligenstein 2 present this information? 3 A. At an internal educational 4 conference we had. 5 Q. Is this a periodic occurrence, 6 these conferences, do they happen on a yearly 7 basis or is this something that just comes up as 8 the need arises? 9 A. No, this was a new conference 10 for us. 11 Q. Does the conference involve 12 drugs manufactured by Lilly other than Fluoxetine 13 or was this a Fluoxetine conference? 14 A. It was on all drugs that Lilly 15 is working on. 16 Q. How long did the conference 17 last? 18 A. About one week. 19 Q. Where was it held? 20 A. In Indianapolis. 21 Q. Were you given any written 22 materials during the conference? 23 A. No. 24 Q. Were you given any written Page 16 1 materials before the conference? 2 A. Yes, I got an educational 3 notebook. 4 Q. What was contained in the 5 educational notebook with regards to Fluoxetine? 6 A. I do not know if anything was 7 in the notebook on Fluoxetine, I do not recall. 8 Q. The results of Doctor 9 Heiligenstein's study that he presented at the 10 conference, were they contained in the notebook 11 in any form? 12 A. I do not believe so. I would 13 need to check to verify, but I do not believe so. 14 Q. Have you heard of the phrase 15 Prozac safety team? 16 A. I'm aware of the phrase. 17 Q. Were you a member of the safety 18 team? 19 A. Yes. 20 Q. What was your function within 21 the team? 22 A. I believe my function was to 23 help coordinate and distribute projects to team 24 members. I also did safety projects as well. Page 17 1 Q. So mainly two functions, to 2 help coordinate and distribute projects to the 3 safety team members, and then you had your own 4 separate projects as well? 5 A. Right, because I had my own 6 work as part of the safety team. 7 Q. Okay. What types of project 8 would you coordinate and distribute? 9 A. The projects were routine 10 safety reviews. 11 Q. Anything else? 12 A. No. 13 Q. Were you a member of any other 14 drug safety team other than the Prozac safety 15 team? 16 A. You mean in any capacity at 17 Lilly or just on Fluoxetine? 18 Q. In any capacity at Lilly. 19 A. Yes. 20 Q. Were safety teams established 21 for every drug manufactured by Lilly? When I say 22 safety, I mean a formal safety team. 23 A. If you mean was that title of 24 safety team given to any other drugs manufactured Page 18 1 by Lilly, then yes. 2 Q. Okay. Is that done for every 3 drug at Lilly? 4 A. The other safety team to which 5 I am referring was across all drug products. 6 Q. Okay. How do the functions of 7 the safety team that is across all drug products 8 differ from the Prozac, specific Prozac safety 9 team? 10 A. In many ways. There were 11 different people on the teams. 12 Q. Substantively, how did they, 13 not at first format, but substantively how did 14 they differ? 15 A. Could you clarify your 16 question? 17 Q. Sure. What I'm trying to find 18 out is you say -- I see all these documents with 19 Prozac safety team written on them, okay, and I'm 20 just trying to find out if there were similar 21 safety teams set up for every single drug 22 manufactured by Lilly or if this was something 23 that was exclusive to, say, Prozac? 24 A. The other safety team to which Page 19 1 I refer selected different disease entities, and 2 collected information on these disease entities 3 for patients on any Lilly drug. So substantively 4 it was a more limited list of disease entities 5 that was reviewed on the other safety team, and 6 that's probably the primary substantive 7 difference. 8 Q. How about for other drugs at 9 Lilly, was there a sub-safety team, so to speak, 10 set up? 11 A. I do not know. 12 Q. Have you ever been a member of 13 a sub-safety team on any other drug other than 14 Prozac? 15 A. Other than the one to which I 16 refer which was across drug products, no. 17 Q. What other projects did the 18 safety team perform besides routine safety 19 reviews? 20 A. I believe that's all that this 21 safety team did if my memory serves me correctly. 22 Q. When was the Prozac safety team 23 established? 24 A. I do not remember the exact Page 20 1 time it was established. 2 Q. How about a year, can you give 3 me a year? 4 A. Perhaps 1990 or 1991. 5 Q. Was it after Doctor Teicher's 6 article came out? 7 A. I do not recall. 8 Q. Besides yourself, who else was 9 on the safety team? 10 A. I remember that there were a 11 lot of CRAs, clinical research administrators, 12 who were on the team, I cannot recall most of the 13 people's names. 14 Q. Why don't you give me the names 15 of those people that you can recall. 16 A. I believe Kelly Purcell was 17 one, Katie Copley-Merriman was another. 18 MR. RUIZ: What was that name? 19 THE WITNESS: Katie Copley-Merriman. 20 A. And a host of others that I 21 just can't recall. 22 Q. Leslie Chiplis? 23 A. She could have been a member. 24 Q. David Goldstein? Page 21 1 A. Yes, I believe he was a member. 2 Q. Dena Marvel? 3 A. Probably. 4 Q. Rebecca McHenry? 5 A. Maybe. 6 Q. Do you have Exhibit 3, do you 7 still have Exhibit 3? 8 A. Yes. 9 Q. Look at the list on the upper 10 left-hand corner and tell me which of those 11 people -- 12 A. Which list do you want me to 13 look at? 14 Q. The entire list, the To and CC. 15 Tell me which of those people comprise the safety 16 team, if not all of these people. 17 A. I believe that all of the 18 primary addressees on this memo, and not the 19 co-copy people, were on the safety team. 20 Q. Okay. Anybody in addition to 21 the primary addressees? Obviously you, right, 22 you're not a primary on the list. 23 A. None that I'm aware of. 24 Q. Okay. In Exhibit 3 it talks Page 22 1 about gathering materials on specified topics, 2 correct, the first paragraph of the memo? 3 A. Yes, that is the request in the 4 memo. 5 Q. And it's material that had 6 already been collected. In other words it was a -- 7 the projects were to gather information on these 8 various topics that had already been generated 9 and put them in a library, so to speak; correct? 10 A. That is what the memo says, 11 correct. 12 Q. And then under that there are 13 various topics assigned to various people; 14 correct? 15 A. Yes. 16 Q. And you are assigned the topics 17 of bleeding, dyskinesia movements, and you look 18 like you're a head of a tab on the last one, the 19 suicide proposed EPI studies, correct, at the 20 bottom? 21 A. Correct, the memo says that. 22 Q. After suicide, in parens, it 23 says proposed EPI studies, close paren. Is that 24 an epidemiological study? Page 23 1 A. Yes. 2 Q. And the fact that your name and 3 initial are in parens, does that mean that your 4 project regard is related to the proposed EPI 5 studies? 6 A. I believe that was my primary 7 involvement. 8 Q. What proposed EPI studies are 9 you talking about in that memo? 10 A. As I mentioned in our last 11 deposition, we received proposals from outside 12 investigators to conduct epidemiological studies 13 of suicidality, and I reviewed these proposals. 14 Q. Did you ever take anybody up on 15 their offer to conduct a proposed EPI study? 16 A. At the time I was involved in 17 this, we did not pursue any of the proposed 18 studies. 19 Q. Why not? 20 A. Primarily because of the 21 scientific limitations of the studies proposed. 22 Q. Each of them had their own 23 scientific limitations or epidemiological studies 24 have scientific limitations generally. Page 24 1 A. I believe both of those 2 statements are correct. 3 Q. At any time did Lilly consider 4 performing an epidemiological study on suicide? 5 A. We evaluated that option. 6 Q. And what was the result of the 7 evaluation? 8 A. The evaluation was that the 9 work we were doing with the meta-analyses was a 10 better approach than an epidemiological study. 11 Q. How does the meta-analysis 12 differ from an epidemiological study? 13 A. The meta-analysis study 14 included clinical trials. Epidemiological 15 studies are observational studies, they're not 16 clinical trials. 17 Q. Sort of like the overdose study 18 that Doctor Heiligenstein is performing now? 19 A. The overdose study to which you 20 refer is an epidemiological study. 21 Q. Did you consider a study such 22 as Doctor Heiligenstein's overdose study when you 23 reviewed the possibility of performing an 24 epidemiological study on suicide back in November Page 25 1 of 1990? 2 A. I do not recall that we did. 3 Q. Did you have any 4 responsibilities in gathering previously 5 collected data on suicidality? 6 A. I'm sorry, could you rephrase 7 your question, please? 8 Q. Sure. In Exhibit 3, it talks 9 about gathering previously collected materials on 10 these various subjects, right? 11 A. Yes. 12 Q. And the purpose for doing that 13 is to create a library, so to speak, so that work 14 would not be duplicated; correct? 15 A. I do not know if the purpose of 16 the library was to avoid duplication, but the 17 memo does say gathering materials for creating a 18 library. 19 Q. Regardless, you were going to 20 gather preexisting materials, preexisting from 21 this date, November 14, 1990, and put them in a 22 library; correct, create a library? 23 A. Correct. 24 Q. What materials did you gather Page 26 1 related to the subject of suicide under those 2 parameters? 3 A. I believe regarding the 4 proposed epidemiological studies, I received a 5 number of study proposals from outside 6 investigators that would have been the collection 7 of information I had. 8 Q. Other than the proposed studies 9 by outside investigators, did you collect any 10 other preexisting information regarding suicide 11 or suicidality to put in a library? 12 A. Not that I can recall. 13 Q. Okay. What about 14 dyskinesia-movement disorders, what kind of 15 materials did you gather with regards to that 16 subject? 17 A. As part of my job, I did a lot 18 of work on dyskinesia-movement disorders, and 19 anything I would have done, I would have 20 collected it in a file. 21 Q. Okay. Where was this library 22 located ultimately? 23 A. I believe this library never 24 got centralized in any location, I believe people Page 27 1 had their own work in their files, in their own 2 respective files. 3 Q. Was there an index of 4 everybody's individual work that was kept? 5 A. I do not believe so. 6 Q. So basically this project was 7 never completed, is that what you're saying? 8 MR. MYERS: I object to the form, I 9 don't think that's what he said. He said it 10 never got centralized. 11 A. The work was underway, I 12 believe, but I do not believe that a central 13 library held all the documents, I believe the 14 documents were held by the individuals. 15 Q. At the end of the first 16 paragraph, it says -- well, it says following 17 topics listed alphabetically and associated names 18 are responsible for gathering materials to the 19 specified topic which have already been collected 20 and for providing these materials to Dena Marvel, 21 temporary librarian, by November 30, 1990; 22 correct? 23 A. Correct, the memo says that. 24 Q. So were these materials that Page 28 1 were provided to Dena Marvel? 2 A. I do not know. 3 Q. Did you provide information to 4 Dena Marvel? 5 A. I do not believe I did. 6 Q. Why not? 7 A. I believe the focus is on doing 8 the work moreso than worrying about a process of 9 having central collection. As I recall, the work 10 was kept in individual's files. 11 Q. But this specific project was 12 related to gathering preexisting material; 13 correct? 14 A. The memo does say that. 15 Q. So it wouldn't be a matter of 16 having to set aside work on these projects 17 because the work had already been done; correct, 18 if they had been done? 19 A. I do not know to what level the 20 materials were gathered. 21 MS. ZETTLER: Can you read back my last 22 question, please? 23 (THE COURT REPORTER READ BACK THE 24 REQUESTED TESTIMONY.) Page 29 1 Q. My question is: The memo 2 specifically says to gather information that had 3 already been produced, does it not? 4 A. The memo does say that these 5 topics, and the names associated with the topics, 6 these persons were responsible for gathering the 7 materials on this specific topic, which have 8 already been collected. 9 Q. And in fact it gives a deadline 10 for when these materials should be turned over to 11 Ms. Marvel, right? 12 A. It does. 13 Q. And that deadline is 14 approximately sixteen days after the date of the 15 E-mail or memo, is it not? 16 A. Yes. 17 Q. And it's your testimony that 18 nobody turned over their information to Ms. 19 Marvel or you just didn't turn over your 20 information to Ms. Marvel? 21 MR. MYERS: He's already answered that. 22 A. I do not know if or when others 23 turned over information to Ms. Marvel, I did not 24 turn over information to Ms. Marvel. Page 30 1 Q. Okay. Wasn't it your job to 2 find out whether or not this task had actually 3 been completed? After all, you testified earlier 4 that one of your duties involved in the team was 5 to coordinate and distribute projects; correct? 6 MR. MYERS: You've asked him two 7 questions. Which one do you want him to answer? 8 MS. ZETTLER: I think it's all 9 encompassed in the same question. 10 MR. MYERS: I object to the form. 11 Answer it if you can, Doctor. 12 A. I did testify that one of my 13 roles was to coordinate and distribute work load. 14 Q. Did somebody else have the 15 responsibility to make sure these projects got 16 done or was that your responsibility? 17 A. I do not believe that was my 18 responsibility. 19 Q. Whose responsibility was it? 20 A. Presumably the supervisors of 21 each individual. 22 Q. And you're just assuming that, 23 aren't you, you don't know that for a fact? 24 A. I do not know that for a fact. Page 31 1 Q. So you're just guessing. 2 MR. MYERS: No, he's not guessing, he 3 said presumably. 4 Q. Are you guessing, Doctor? 5 A. Each individual is -- or some 6 of the individuals were from different divisions, 7 and they have their own line management so that 8 they would be responsible to their own line 9 management. For these particular projects, I did 10 not have authority over those individuals, their 11 line management did. 12 Q. Were the line management 13 involved in the safety team? 14 A. I do not believe so because I 15 do not recognize any of the names as line 16 management on the safety team. 17 Q. Who was the head of the safety 18 team? 19 MS. HUFF: I didn't understand that 20 question. 21 MS. ZETTLER: Who was the head of the 22 safety team. 23 A. And by head, could you help me 24 by explaining what you mean by that? Page 32 1 Q. Who was the leader of the 2 safety team? 3 A. I believe I said I coordinated 4 and distributed work load. 5 Q. Right, but you also said that 6 you had no authority over anybody on the safety 7 team to make sure that their jobs got done, and I 8 want to know who had authority to make sure that 9 their jobs got done. 10 MR. MYERS: He's already answered that. 11 A. I believe I answered that. 12 Q. Was there one person besides 13 you who was responsible for coordinating the 14 actions of the safety team? 15 A. I suppose of all the persons, 16 that Bob Zerbe would have had the umbrella 17 coverage of everybody. 18 Q. Who did you answer to in your 19 capacity as coordinator of the safety team? 20 A. I believe I reported to Bob 21 Zerbe. 22 Q. Was he the person who ran the 23 safety team? 24 A. I don't know what you mean by Page 33 1 run the safety team, but as I was the coordinator 2 of distributing projects, and I reported -- I 3 believe I reported to Zerbe at that time, by 4 inference one could assume that he's the name -- 5 he's the person who you're looking for. 6 Q. Who set the date of November 7 30, 1990 for the deadline to turn over the 8 information to Dena Marvel? 9 A. The safety team did. 10 Q. And who on the safety team? 11 A. I believe the people listed as 12 primary addressees talked about this in a 13 meeting. 14 Q. Who ran the meeting or was it 15 just a free for all? 16 A. I believe I set up the meeting. 17 Q. Okay. Did you, in effect, 18 chair the meeting? 19 A. Yes. 20 Q. Was there anybody else present 21 who had authority over you at that meeting? 22 A. No. 23 Q. Were there other meetings that 24 were held? Page 34 1 MR. MYERS: Safety team meetings? 2 MS. ZETTLER: Right. 3 A. I do not recall if we had other 4 meetings, I think we did, but I do not recall. 5 Q. What other projects did the 6 safety team do besides the failed data collection 7 project? 8 MR. MYERS: I object to the form, there 9 was no testimony that it was failed. 10 A. I can only refer to this memo 11 to see the topics of work that the safety team 12 did. 13 Q. So does the memo indicate to 14 you that the safety team was in existence before 15 this memo? 16 A. I do not know if it was in 17 existence before this memo, I do not recall when 18 it was set up. 19 Q. Were you involved in the safety 20 team from its inception? 21 A. Yes, I believe so. 22 Q. Who asked you to be involved in 23 the team? 24 A. I believe it was Bob Zerbe. Page 35 1 Q. Did he tell you he wanted you 2 to basically head up the team? 3 A. As I have stated earlier, I 4 coordinated and brought together the team. 5 Q. If somebody had a question on -- 6 somebody that was on the team had a question on 7 how something should be -- what information 8 should be included in the data gathering project 9 or how something should be turned over to Ms. 10 Marvel, who would they go to, would they ask you? 11 A. Do you mean people outside of 12 the safety team? 13 Q. No, people on the safety team. 14 A. I believe those issues were 15 discussed within this particular safety team 16 meeting. 17 Q. Okay. The meeting which you 18 chaired? 19 A. The meeting -- yes, the meeting 20 which I chaired. And those types of details were 21 presumably worked out at that meeting amongst all 22 the members. 23 Q. Was there anybody else on the 24 same level as you on the safety team as far as Page 36 1 authority? 2 A. The other person on the safety 3 team who was also a clinical research physician 4 is David Goldstein. 5 Q. That's not my question. My 6 question is: Is there anybody else that was on 7 the team that had the same authority over the 8 team that you had? 9 A. No. 10 Q. Okay. 11 (PLAINTIFFS' EXHIBIT NO. 4 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Could you take a look at that, 15 please, Doctor. 16 A. (Witness complies.) 17 Q. Have you had a chance to review 18 Exhibit 4? 19 A. Yes. I believe it's listed 20 Exhibit 5. This is Exhibit 4 now. 21 Q. And the first page of Exhibit 4 22 is another E-mail written by you; correct? 23 A. Correct. 24 Q. And it's also dated November Page 37 1 14, 1990, the same as Exhibit 3; correct? 2 A. November 14, 1990, correct. 3 Q. This appears to be an E-mail 4 to, it looks like other clinical research 5 physicians, does it not? 6 A. Yes. 7 Q. Are all those people on the 8 primary addressee list clinical research 9 physicians? 10 A. Yes. 11 Q. And in this memo, you're 12 telling them that the people who were members of 13 the Prozac safety team was going to approach them 14 to gather documents and information from that 15 that are already existing on those topics that 16 are listed in Exhibit 3; correct? 17 A. Yes. 18 Q. Did you contact Doctors 19 Beasley, Chappel, Heiligenstein, Satterlee, 20 Street, Thompson and Wheadon regarding the 21 epidemiology project? 22 A. I do not recall, but probably 23 so. 24 Q. Did you gather information from Page 38 1 them regarding that project? 2 A. I do not recall if I gathered 3 information from them. 4 Q. Did you approach each of these 5 people and ask for information about movement 6 disorders or dyskinesia? 7 A. I recall seeking that 8 information, yes. 9 Q. From each of them? 10 A. I do not recall if it was each 11 of them, but I recall seeking that information 12 from at least some of them. 13 Q. Who do you recall seeking 14 information from? 15 A. Charles Beasley. 16 Q. Anybody else? 17 A. David Wheadon. 18 Q. Anybody else? 19 A. Perhaps Jamie Street. 20 Q. Anybody else? 21 A. Not that I can recall. 22 Q. Did any of those people turn 23 over information to you? 24 A. I do not recall if I got Page 39 1 information from them. 2 Q. How about documents? 3 A. I believe I got some 4 information from -- or documents from Charles 5 Beasley. 6 Q. Related to dyskinesia-movement 7 disorders? 8 A. Yes. 9 Q. What did you do with those 10 documents? 11 A. I recall keeping them in my 12 file. 13 Q. Okay. Mr. Myers made an 14 objection earlier when I suggested that the 15 documents had not been collected and placed in a 16 library form, and in fact the project had failed. 17 Do you remember that? 18 A. I remember his objection, yes. 19 Q. Is it your testimony that the 20 project was successfully completed? 21 A. How do you define successful 22 completion? 23 Q. Well, if you look at the two 24 exhibits, 3 and 4 together, they state that the Page 40 1 purpose for collecting the information is to have 2 things on file or things available to people so 3 that work is not duplicated; correct? 4 MR. MYERS: I object to the form, I 5 think he already testified about the purpose may 6 not have been to prevent duplication. You asked 7 him that before. 8 MS. ZETTLER: If you read Exhibit 4 -- 9 I think he's pointing out to you where that's the 10 case, Larry. 11 MR. MYERS: Okay. 12 A. I believe this project was 13 successful based on being able to collect 14 pertinent information for each individual topic 15 so that it could be evaluated and avoid 16 redundancy, as stated in the memo. 17 Q. Okay. How was it collected or 18 how was it maintained so that it would avoid 19 redundancy? 20 A. If someone were working on a 21 particular project, they would collect 22 information previously done on that project and 23 build on that project, not necessarily redoing 24 what had been done previously. Page 41 1 Q. What if you were assigned a 2 project on, say, violent aggressive behavior and 3 the use of suicide, how would you find out -- I'm 4 sorry, and the use of Prozac. How would you find 5 out what had been collected on that subject or 6 what had already been done on that subject? 7 A. Could you repeat the question, 8 please? 9 Q. Sure. If you were assigned -- 10 let me ask it this way: On Exhibit 4, you are 11 assigned various subjects; correct, bleeding, 12 dyskinesia-movements and suicide proposed EPI 13 studies, right? 14 A. On the second page of Exhibit 4 -- 15 Q. Right. 16 A. -- there is an assignment list, 17 correct. 18 Q. And on that assignment list you 19 are given the specific assignments of bleeding, 20 dyskinesia-movements and suicide proposed EPI 21 studies; correct? 22 A. Correct. 23 Q. If I'm understanding your 24 testimony, at least you collected information on Page 42 1 those various topics and kept those in your area 2 or in your files; correct? 3 A. Correct. 4 Q. Now, if you were assigned then 5 a project related to, say, overdose, how would 6 you -- where would you go to find whatever else 7 had been done on that subject prior to your 8 assignment to that subject? 9 A. I would have gone to the person 10 who at the time I was aware was working on it and 11 ask them for the information. 12 Q. So you're assuming that if it 13 was somebody other than Rod Usher, that Mister 14 Usher would have transferred all of his files to 15 the person who was working on it? 16 A. No, I believe Rod would have 17 obtained the information from others. 18 Q. Right, but I'm asking -- you 19 testified that you believe that this project was 20 successfully completed, the data gathering 21 project; correct? 22 A. Based on the way I define 23 successful completion. 24 Q. What is your definition of Page 43 1 successful completion then? 2 A. That I completed the projects I 3 was assigned. 4 Q. What about the team as a whole, 5 did they successfully complete this project? 6 A. I testified earlier, I do not 7 know if they completed collection of the 8 information. 9 Q. Did Dena Marvel ever come to 10 you and ask you to turn over the documents and 11 information that you collected on your assigned 12 subject? 13 A. I do not recall. 14 Q. Do you know if she ever had a 15 problem with collecting documents or information 16 from the other members of the Prozac safety team? 17 A. I do not recall. 18 Q. Did you continue working on 19 Fluoxetine related safety projects after November 20 14, 1990? 21 A. Selected Prozac safety 22 projects, yes. 23 Q. Which projects? 24 A. I believe the bleeding and Page 44 1 dyskinesia-movement disorders were two projects I 2 continued working on, and I believe I continued 3 to review epidemiology study proposals. 4 Q. Any others? 5 A. Not ones where I was directly 6 responsible. 7 Q. How about indirect 8 responsibility? 9 A. Yes. 10 Q. What projects did you have 11 indirect responsibility for? 12 A. I recall working on addiction 13 and withdrawal, aplastic anemia, frequency of 14 adverse drug reactions, pulmonary. 15 Q. Hostility violence? 16 A. Other than my prior testimony 17 of reviewing a report that John Heiligenstein had 18 once written, I had no other involvement in that. 19 Q. Overdose? 20 A. Other than hearing a 21 presentation of the overdose study and 22 preliminary results which I mentioned earlier in 23 this deposition, I had no other direct or 24 indirect responsibility for the particular Page 45 1 project. However, I was one of the research 2 physicians who signed off on adverse drug 3 reactions, so obviously any of these safety 4 events would have been looked at by me. So I 5 just wanted to point that out. 6 Q. We'll get to that later on, 7 Doctor. Did you have any responsibility, direct 8 or indirect, specific or general, related to the 9 preparation for the advisory committee meeting 10 that was held in September of 1991 on Fluoxetine? 11 A. I had responsibility for 12 preparing some back-up information for the 13 September, 1991 advisory committee meeting on 14 antidepressants. 15 Q. Did you prepare back-up 16 information on any antidepressants other than 17 Fluoxetine? 18 A. I prepared back-up information 19 on Fluoxetine and other antidepressants. 20 Q. What type of back-up 21 information did you prepare on other 22 antidepressants? 23 A. We looked at DAWN data, ER 24 mentions and medical examiner mentions of Page 46 1 Fluoxetine and other antidepressants. 2 Q. Anything else? 3 A. Not that I can recall. 4 Q. Was an index of the documents 5 and information gathered as a result of the 6 Prozac safety team data gathering project ever 7 created? 8 A. What do you mean by index, do 9 you mean assigning volume numbers to the 10 information, the location of storage or what are 11 you looking for? 12 Q. Some indication of what had 13 been collected and where it was being stored so 14 that if you wanted to go find information that 15 had been collected on a subject that was not your 16 specific assignment, you could do so. 17 A. I suppose the index was the 18 assignments on this memo. So the person would go 19 to the individual assigned and ask them for the 20 information. 21 Q. What happened if the 22 information was -- if the individual either left 23 Lilly or was no longer assigned to that area as a 24 member of the safety team? Page 47 1 A. I do not know how each 2 individual handled their files. 3 Q. Do you still have all the 4 suicide proposed EPI information that you 5 gathered in your files? 6 A. I do not believe I have that 7 particular information in my files any longer, I 8 believe I turned them over to our legal group. 9 Q. Are you still a member of the 10 safety team, Prozac safety team? 11 A. No. 12 Q. What did you do with your 13 Prozac safety team information when you stopped 14 being a member of the team? 15 A. Most, if not all, was turned 16 over to legal. For completed reports, which were 17 submitted to the FDA, they would be in our 18 regulatory files. 19 Q. You had completed reports on 20 dyskinesia-movement disorders, bleeding events 21 and suicide in your files? 22 A. At the time I had completed 23 reports on bleeding, dyskinesia-movement 24 disorders and pulmonary, I recall, which we Page 48 1 turned over to legal. 2 Q. Did everybody in the safety 3 team turn their safety team documents over to 4 legal? 5 A. Presumably. 6 Q. So if you needed to go and look 7 at the information that was gathered as a part of 8 this project talked about in Exhibits 3 and 4, 9 you would have to go to the legal department to 10 get that information now? 11 A. If you're asking me where I 12 would go? 13 Q. Uh-huh, yes. 14 A. Then, yes, that would probably 15 be a good starting point. 16 MS. ZETTLER: Let's take a break. 17 (A SHORT RECESS WAS TAKEN.) 18 Q. Who is Seymore Fisher? 19 A. I recall that he is a gentleman 20 that sent an epidemiology proposal for review. 21 Q. And you guys turned that down, 22 didn't you? 23 A. I believe so. 24 Q. Did you ever have any other Page 49 1 contact with Doctor Fisher? 2 A. Other than through written 3 correspondence, I do not believe so. 4 Q. Are you aware that Doctor 5 Fisher performed a study on Fluoxetine comparing 6 it to Desyrel? 7 A. I believe at the time he wanted 8 to perform it or was performing it, so I'm aware 9 of that study. 10 Q. And that the results of Doctor 11 Fisher's study indicated that as far as 12 suicidality went, there was a worse incidence of 13 Prozac suicidality as compared to Desyrel 14 suicidality? 15 A. I'm not aware of his results. 16 (PLAINTIFFS' EXHIBIT NO. 5 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 A. I'm sorry what was your 20 question? 21 Q. My last question is whether or 22 not -- 23 MS. ZETTLER: Go ahead and read it 24 back. Page 50 1 (THE COURT REPORTER READ BACK THE 2 REQUESTED TESTIMONY.) 3 Q. I realize that all the names 4 have been blacked out in this exhibit, Doctor 5 Kotsanos, but does this refresh your recollection 6 as to whether or not you were aware of Doctor 7 Fisher's results -- the results of Doctor 8 Fisher's study? 9 A. Obviously I got this memo which 10 told me what his results would be or would be 11 presented, but I don't recall that's what his 12 results were. 13 Q. Did you talk to Doctor Beasley 14 or Doctor Thompson about your contacts, previous 15 contacts with Doctor Fisher? 16 A. This memo helps me recall that 17 Doctor Thompson, I believe, forwarded the 18 proposal to me which I reviewed and responded in 19 writing, that's what I recall. 20 Q. Do you recall Doctor Fisher's 21 proposal specifically? 22 A. No. 23 Q. It says in here that the study 24 he ultimately did was a surveillance comparison Page 51 1 between Prozac and Triavil. Does that indicate 2 to you that it was a study similar to the 3 overdose study that's being performed now where 4 people who presented with overdose or some other 5 problem were followed? 6 A. I do not know, I do not recall. 7 Q. Did you ever talk to or write 8 to Doctor Fisher as a result of this memo, 9 Exhibit 5? 10 A. I believe I wrote a letter to 11 him about his proposal. 12 Q. Okay. But after this 13 memorandum, did you write to Doctor Fisher or 14 speak to him or contact him in any way regarding 15 the results of his surveillance study comparing 16 Prozac and Desyrel? 17 A. I do not recall if I did. 18 Q. Do you recall if anybody from 19 Lilly contacted Doctor Fisher? 20 A. I don't know. 21 Q. Have you ever contacted Doctor 22 Teicher, Martin Teicher? 23 A. No, I have never contacted 24 Doctor Martin Teicher. Page 52 1 Q. Have you ever talked to Doctor 2 Jonathan Cole? 3 A. I do not recall if I did, I may 4 have. 5 Q. Are you aware of any studies 6 done by Lilly regarding suicide prior to 1990? 7 A. Not that I'm aware of. 8 Q. Are you aware of any studies 9 that were done on violent aggressive behavior 10 prior to 1990? 11 A. Other than the John 12 Heiligenstein's study that we previously 13 discussed, I'm unaware of any others. 14 Q. Doctor Heiligenstein's study 15 was started prior to 1990? 16 A. I maybe got the dates wrong, 17 no, I don't think so, none that I'm aware of. 18 Q. How about studies done with 19 regards to Fluoxetine and agitation prior to 20 1990? 21 A. None that I'm aware of or that 22 I recall. 23 Q. How about studies related to 24 anxiety and Fluoxetine prior to 1990? Page 53 1 A. I cannot recall if Lilly was 2 doing any anxiety studies prior to 1990. 3 Q. How about any of those studies 4 after 1990, suicide, hostility, violent 5 aggressive behavior, anxiety, agitation? 6 A. What's your specific question? 7 Q. Are you aware of any studies 8 that were done by Lilly regarding any of those 9 topics after 1990? 10 A. Yes, the ones we reviewed in 11 this deposition and others in the other 12 deposition. 13 Q. Doctor Heiligenstein's overdose 14 study? 15 A. That's one of them. The 16 meta-analysis study, the violence report by 17 Doctor Heiligenstein, so, yes. 18 Q. How about clinical trials? 19 A. Clinical trials of what? 20 Q. Any of those subjects that I 21 just set out, suicide, violent aggressive 22 behavior, hostility, agitation, anxiety? 23 A. None that I'm aware of. 24 (PLAINTIFFS' EXHIBIT NO. 6 WAS Page 54 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 Q. Do you recognize Exhibit 6, 4 Doctor? 5 A. I do not. 6 Q. Have you ever seen a document 7 similar to this? 8 MR. MYERS: Before he answers, let me 9 just, for the record, state that that appears to 10 be, to me, several similar looking documents. I 11 don't know that it is one and the same, but it's 12 one document. It could be a compilation of 13 similar appearing documents. 14 Q. Do you recognize any of these 15 documents comprising Exhibit 6? 16 A. I do not recall seeing this 17 document, I could have, but I do not recall 18 seeing it. 19 Q. When did you leave the Prozac 20 safety team? 21 A. My involvement came to an end 22 after the advisory committee meeting, 23 thereabouts. 24 Q. In September of 1991? Page 55 1 A. Yes. 2 Q. Are you familiar with any of 3 the contents of these pages, like the assignments 4 and things of that nature? 5 A. It might be more helpful if you 6 can target particular ones. 7 Q. Look at the first page. 8 A. Okay. 9 Q. Do you recall a meeting that 10 was to be held between the FDA and Lilly 11 employees in November -- or, I'm sorry, September 12 of, looks like, 1990? 13 A. I remember mentioning in our 14 other deposition that there were meetings at the 15 FDA I attended. Whether or not -- I presume this 16 meeting mentioned on the first page of this 17 document refers to that meeting and not the 18 September 1991 advisory committee meeting. 19 Q. Okay. Do you recall attending 20 a meeting at the FDA in September of 1990? 21 A. I recall attending a meeting at 22 the FDA. Whether or not it was September, 1990, 23 I do not know. 24 Q. Do you recall preparing for a Page 56 1 meeting in September of 1990? 2 MR. MYERS: At the FDA? 3 MS. ZETTLER: Right. 4 A. I do not recall specifics of 5 any preparation, but I do recall being at an FDA 6 meeting. 7 Q. What's the last specific 8 meeting you remember attending related to 9 Fluoxetine with personnel from the FDA? 10 A. The advisory committee meeting 11 in September, 1991. 12 Q. What did you do at that 13 meeting? 14 A. I listened to the discussion 15 that took place. 16 Q. What was your purpose for being 17 there? 18 A. I had prepared back-up 19 materials for selected topics in the event that 20 they came up for discussion. 21 Q. How long were you at the 22 meeting, how many days were you up there? 23 A. I believe it was a one-day 24 meeting. Page 57 1 Q. Were you there for any longer 2 than one day? 3 A. I believe we arrived the night 4 before. 5 Q. When was the last Fluoxetine 6 related task you recall working on generally? 7 A. I'm currently involved in the 8 health economics research division's work, as I 9 mentioned last time, so we've been involved in 10 discussions of a cost effectiveness decision 11 analysis model of Fluoxetine. So that's recent 12 involvement. 13 Q. Other than your current 14 involvement with Fluoxetine, when is the last 15 project you recall working on with regards to 16 Fluoxetine? 17 MR. MYERS: Before he went into the 18 health economics area? 19 MS. ZETTLER: Right. 20 A. Completing the letter to the 21 editor to the American Journal of Public Health 22 on trends in suicide rates and Fluoxetine 23 introduction. 24 Q. Okay. Exhibit 6 says at the Page 58 1 bottom, FDA meeting 9-25, lead person Kotsanos, 2 Webber, next steps. Is this your handwriting on 3 the first page of this document? 4 A. It does not look like my 5 handwriting. 6 Q. So does that mean no, it's not 7 your handwriting? 8 A. No, I do not think it is. 9 Q. There's four bullet points 10 under next step that appear to be assigned to you 11 and Doctor Webber; correct? 12 A. According to the memo, yes. 13 Q. Do you recall any of these 14 assignments? 15 A. I recall working on bleeding 16 and pulmonary analysis. 17 Q. Do you recall working on a 18 proposed agenda for the meeting with the FDA? 19 A. No, I do not recall 20 specifically working on a proposed agenda. 21 Q. What does it mean at the bottom 22 where it says schedule for internal review, do 23 you know? 24 A. No. Page 59 1 Q. On the second page it says FDA 2 meeting again. Do you see that, the third point 3 down? 4 A. Yes, I see that. 5 Q. That is the person assigned, 6 you and Doctor Webber; correct? 7 A. Correct. 8 Q. And then after that it has next 9 steps, and it talks about a meeting date being 10 scheduled for 9-25, Leigh Thompson chairing the 11 meeting for Lilly, and bleeding and pulmonary 12 analyses pending, and a letter to the FDA 13 regarding the proposed agenda; correct? 14 A. It states that, yes. 15 Q. Did you and Doctor Webber write 16 the letter to the FDA regarding -- or write a 17 letter to the FDA proposing an agenda for the 18 safety meeting? 19 A. I do not recall if I wrote a 20 letter on the agenda for this meeting. 21 Q. Do you know who requested the 22 safety meeting? 23 A. I do not recall that. 24 (PLAINTIFFS' EXHIBIT NO. 7 WAS Page 60 1 MARKED FOR IDENTIFICATION AND 2 RECEIVED IN EVIDENCE.) 3 Q. Okay, Doctor Katsanos, does 4 this letter refresh your recollection regarding 5 the safety meeting that was requested by Eli 6 Lilly for sometime in 1990, late 1990? 7 A. I vaguely recall a meeting that 8 was being arranged to discuss these topics. 9 Q. Okay. And that was at Lilly's 10 request? 11 A. I do not know, but if I 12 interpret this letter, the exhibit that you gave 13 me, that's what it seems like. 14 Q. Okay. Do you know why Lilly 15 would request such a meeting? 16 A. The only thing I can do is 17 refer to the letter, which says requesting a 18 meeting to present a summary of our safety 19 experience with Prozac during the first two years 20 of marketing. But I do not know more than that. 21 Q. Other than Fluoxetine, what 22 drugs were discussed at the advisory committee 23 meeting in September of 1991? 24 A. I do not recall the other drugs Page 61 1 that were discussed. 2 Q. How much time would you say was 3 spent by the committee listening to or discussing 4 topics related to specifically Fluoxetine? 5 A. I do not recall the exact 6 amount of time. 7 Q. I'm not asking for an exact 8 amount of time, I'm asking for your best 9 estimate. 10 A. I do not recall, presumably 11 most of the day. 12 Q. More than fifty percent? 13 A. Yes. 14 Q. More than seventy-five percent? 15 A. I do not recall that, but 16 certainly more than fifty percent. 17 Q. Did other drug companies other 18 than Lilly present information at that meeting? 19 A. I do not think so, I don't 20 recall any other drug companies presenting at it. 21 Q. Do you know if any other drug 22 companies were invited to participate in the 23 advisory committee meeting? 24 A. I do not recall if they were. Page 62 1 Q. Why do you say the meeting was 2 antidepressants in general? 3 A. That was the title of the 4 meeting. 5 Q. Who made up that title? 6 A. I do not know specifically, but 7 I presume the FDA sets the title of the meetings. 8 Q. Are you familiar with any of 9 the members of the advisory committee itself? 10 A. What do you mean by familiar? 11 Q. Did any of the members of the 12 advisory committee work for Eli Lilly either on 13 Fluoxetine or any other Lilly product, for 14 instance Doctor David Dunner? 15 A. I do not know. 16 Q. Did you work with any of the 17 members of the advisory committee as clinical 18 investigators? 19 A. I did not. 20 Q. Would that be a problem for you 21 as far as the objectivity of the members of the 22 committee if they had worked with Eli Lilly on 23 Fluoxetine clinical trials, ethically? 24 A. What do you mean a problem? Page 63 1 Q. Ethically would that be a 2 problem for you with regards to possible bias on 3 the part of members of the committee if they had 4 in fact worked as clinical investigators on 5 Fluoxetine clinical trials? 6 A. As long as disclosure is made 7 to that effect, no, I would not have a problem 8 with that. 9 Q. You don't think there's an 10 inherent bias in that somebody who worked and had 11 been paid by Lilly on a particular drug in 12 reviewing the safety and efficacy of that 13 particular drug, is that what you're saying? 14 A. That could be a debatable 15 point, but I don't have a problem with that. 16 Q. Why not? 17 A. It's my opinion. 18 Q. Based on what? 19 A. I believe if disclosure is made 20 publicly, then it's up to each individual to form 21 their opinion on that, and in my opinion I don't 22 have a problem with that. 23 Q. As long as disclosure is made 24 publicly? Page 64 1 A. That's my opinion, sure. 2 Q. What if disclosure is made to 3 the FDA but not publicly? 4 A. Well, in a sense the FDA 5 represents the public, so it's a disclosure 6 nonetheless. 7 Q. So you're assuming that a 8 disclosure to the FDA is a disclosure to the 9 public in general? 10 MR. MYERS: I object to the form, 11 that's not what he said. 12 MS. ZETTLER: I'm just trying to find 13 out what he means. 14 A. I would be comfortable with a 15 disclosure to the FDA, to get back to your 16 original question. 17 Q. Even if the public in general 18 was not made aware of the conflict of interest? 19 MR. MYERS: I object to the form. 20 You're assuming a conflict of interest. 21 A. In my opinion, I would be 22 comfortable with that level of disclosure. 23 Q. What did Lilly do in 24 preparation for the safety meeting in 1990? Page 65 1 A. I believe we pulled together a 2 document summarizing these different safety items 3 and submitted it. 4 Q. What information was pulled 5 together on the first point, hostility violence? 6 A. I do not recall, I need to read 7 that document. 8 Q. How about suicidal acts and 9 ideation? 10 A. Again, I do not recall 11 specifically what part of that document was for 12 suicide, suicidal acts and ideation, I would need 13 to review that. 14 Q. Did you work on any slides or 15 anything else for presentation at the meeting? 16 A. I do not recall if I put 17 together any slides, I could have, but I don't 18 recall. 19 Q. Anything else? 20 A. Well, I remember working on the 21 bleeding report, and I remember indirectly 22 working on the pulmonary report. 23 Q. Who requested the advisory 24 committee meeting in September of 1991? Page 66 1 A. I do not know. 2 Q. Do you know if it was a request 3 made by Lilly? 4 A. I do not know. 5 (PLAINTIFFS' EXHIBIT NO. 8 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Okay. Does this refresh your 9 recollection as to whether or not the meeting was 10 held on September 20, 1990? 11 A. According to this exhibit, yes, 12 the meeting was held in September, 1990. 13 Q. Do you recall attending a 14 meeting at the FDA on September 20th of 1990 15 discussing the various safety aspects of 16 Fluoxetine? 17 A. I seem to recall attending a 18 meeting that discussed these safety events, and 19 given that it's September of 1990, then, yes. 20 Q. Have you attended meetings with 21 the FDA regarding other Lilly products besides 22 Fluoxetine? 23 A. Yes. 24 Q. How many different products? Page 67 1 A. Two other products that I can 2 recall. 3 Q. How many other safety meetings 4 did you attend at the FDA on those other 5 products? 6 A. I do not recall the number of 7 meetings. 8 Q. Would you say that you attended 9 more Prozac safety meetings than you did with the 10 other products? 11 A. I do not think so. 12 Q. What situations would you be 13 involved in safety meetings on products, is it a 14 routine thing? 15 MR. MYERS: For him to be involved? 16 MS. ZETTLER: Right. 17 A. On products on which I did 18 specific projects, where an FDA meeting were 19 involved, then it would be routine that I would 20 attend. 21 Q. Are safety meetings held 22 between drug manufacturers and the FDA on a 23 regular basis? 24 A. I do not know. Page 68 1 Q. Would you attend safety 2 meetings on the other products at regular 3 intervals, like, say, every six months or yearly 4 or things of that nature? 5 A. I was not involved in periodic 6 meetings, safety meetings with the FDA. 7 Q. When was the first safety 8 meeting you ever attended at the FDA in your 9 employ at Lilly? 10 A. I believe it was a combined 11 safety and efficacy meeting to review the data of 12 one of our investigational products. 13 A. When was that? 14 A. Before 1990. 15 Q. How long before 1990? 16 A. It could have been 1988 or 17 1989. 18 Q. How about Fluoxetine, when was 19 the first safety meeting that you attended on 20 Fluoxetine with the FDA? 21 A. I do not recall. 22 Q. Were there meetings before the 23 September 25th, 1990 meeting? 24 A. Not that I recall. Page 69 1 Q. Do you recall whether or not 2 this meeting was requested by Lilly to review 3 safety as a result of the Doctor Teicher article 4 that came out in early 1990? 5 MR. MYERS: This one, September 25th? 6 MS. ZETTLER: Right. 7 A. Not that I recall. 8 Q. To your knowledge does Lilly 9 ask for meetings, safety meetings, to review 10 post-marketing safety experiences the first two 11 years of marketing of all its products? 12 MR. MYERS: Did you say during or after 13 the first two years? 14 MS. ZETTLER: After. 15 A. Could you repeat your question, 16 please? 17 Q. Sure. To your knowledge does 18 Lilly, as a rule, request, after a product has 19 been on the market for two years, a safety 20 meeting with the FDA to review their findings 21 post-marketing? 22 A. I do not know if Lilly does 23 that. 24 Q. What role did each of these Page 70 1 individuals set out in Exhibit 8 play at the 2 meeting? 3 A. I do not recall the specific 4 roles of each individual that was at the meeting. 5 Q. Tell me the ones you recall. 6 A. I presume for myself, I was 7 there to talk about bleeding and probably 8 pulmonary events. 9 Q. How about Doctor Beasley, what 10 did he talk about? 11 A. I do not recall. 12 Q. How about Doctor Dornseif? 13 A. I do not recall what he 14 specifically would have discussed or was supposed 15 to have discussed. 16 Q. How about generally? 17 A. Presumably any statistical 18 question. 19 Q. How about Doctor Enas? 20 A. Presumably the same as Doctor 21 Dornseif. 22 Q. What about Doctor or Laura 23 Fludzinski, why was she there? 24 A. I do not know. Page 71 1 Q. How about Gordon -- or Gilad 2 Gordon or Gordon Gilad? 3 A. I do not recall why Gilad was 4 there or if he was there. 5 Q. Do you have a problem with your 6 memory, Doctor? 7 A. No, not at all. 8 Q. Why is it that you can't 9 remember any details of your work on Fluoxetine 10 past the article that you wrote regarding suicide 11 trends in the United States? 12 MR. MYERS: I am going to object to the 13 form, that is argumentative. He's here, he's 14 testifying to what he recalls and what he doesn't 15 recall. 16 A. I would like to address your 17 point, and you said I don't recall beyond the 18 letter to the editor. Your specific question 19 earlier is what was the most recent thing I 20 recall working on, and that was the most recent 21 thing I recalled working on beyond the current 22 work I was doing. 23 Q. What else do you recall working 24 on? Page 72 1 MR. MYERS: When? 2 MS. ZETTLER: Prior to the letter to 3 the editor on the trends in suicidality. 4 MR. MYERS: I object to the question. 5 He's told you a number of things that he's done 6 between the time he came to the company and 7 between the time he went to his present job. Do 8 you want an enumeration of everything he's done? 9 MS. ZETTLER: Yes. 10 MR. MYERS: Well, that's overly broad. 11 Q. With regards to Fluoxetine. We 12 can limit it to suicide at first, if you would 13 like, Doctor. 14 A. My involvement with Fluoxetine 15 and suicide was, to the best of my recollection, 16 to review some of the work that Charles Beasley 17 was doing from an epidemiological standpoint. 18 Also, I worked on the letter to the editor of the 19 American Journal of Public Health looking at 20 trends in suicide rates since Fluoxetine 21 introduction. I reviewed epidemiology proposals 22 to look at suicidality. And I believe that's 23 primarily it to the best of my recollection right 24 now. Page 73 1 Q. How about secondarily? 2 A. What do you mean? 3 Q. You said that's primarily it. 4 MR. MYERS: If you use words like 5 generally or primarily, she'll ask you about 6 specifically and secondarily. 7 MS. ZETTLER: Sure, I try to be 8 thorough. And it seems like you need a lot of 9 help with your memory so I need to help you as 10 much as I can. 11 MR. MYERS: Well, let me tell you this, 12 Ms. Zettler, you're going to conduct this 13 deposition in a civil tone or there's not going 14 to be a deposition. 15 MS. ZETTLER: I don't think there's 16 anything uncivil about the way I just stated 17 that. 18 MR. MYERS: Tell Ms. Zettler if you 19 recall anything secondarily, Doctor. 20 A. Probably the only thing to add 21 to the list I gave you was that I was one of the 22 physicians, among many, that signed adverse drug 23 events which included numerous different safety 24 reports. Page 74 1 Q. When you say safety reports, 2 you mean reports of adverse events? 3 A. Right. 4 Q. During clinical trials? 5 A. Right. 6 Q. Do you recall signing any -- 7 A. Well, not during clinical 8 trials, but for -- I believe they were adverse 9 event reports primarily post-marketing. 10 Q. Did you work as a clinical 11 monitor on any Fluoxetine depression clinical 12 trials? 13 A. No. 14 Q. Have you ever signed any 1639s 15 related to serious events that occurred on 16 clinical trials with Fluoxetine? 17 A. I do not recall if I did, I 18 don't think so, but I do not recall if I did. 19 MS. ZETTLER: See Larry, it helped his 20 memory. 21 MR. MYERS: We developed a wealth of 22 information here. 23 MS. ZETTLER: I just don't want to put 24 Doctor Kotsanos in the embarrassing position of Page 75 1 having him testify at trial and all of a sudden 2 regain his memory. 3 MR. MYERS: He's testifying today as to 4 what he recalls. 5 Q. Is there anything out there 6 that would refresh your recollection as to 7 whether or not there are any other areas on 8 suicidality and Fluoxetine that you worked on? 9 A. I suppose only if you were to 10 show me any of my written work that I had done. 11 Q. All of your written work that's 12 been done has been turned over to the legal 13 department at Lilly, has it not? 14 A. Correct. 15 Q. So if something were to show up 16 at the time of the trial that hadn't been 17 produced prior to trial that would refresh your 18 recollection, that wouldn't be because you didn't 19 turn it over to the legal department; correct? 20 A. I had a hard time following 21 your question. 22 Q. I'm asking you if something -- 23 we've been produced a number of documents with 24 regards to your depositions, Doctor, okay? Page 76 1 A. Okay. 2 Q. And I just wanted to make sure 3 that your written works, all your written works 4 on Fluoxetine were turned over to the legal 5 department at Lilly. 6 A. Absolutely. 7 Q. So if you were to testify at 8 trial, which we probably will, we'll probably ask 9 you to testify at trial, and your recollection 10 were to be refreshed by a document that had not 11 been produced to us previously from the legal 12 department at Lilly, that would not be because 13 you did not turn it over to the legal department 14 at Lilly, would it? 15 MR. MYERS: You're talking about his 16 documents? 17 MS. ZETTLER: His document, his written 18 works as he just said. 19 MR. MYERS: I think he's answered it, 20 he's told you what he turned over. 21 A. To the best of my knowledge, I 22 turned over everything, and I told you about what 23 I recalled from it. 24 Q. Okay. Outside of your written Page 77 1 works, is there anything else that would refresh 2 your recollection as to the work you did on 3 Fluoxetine and suicide? 4 A. I believe I told you everything 5 that I can recall to the best of my memory. 6 Q. Okay. Other than reviewing 7 Doctor Heiligenstein's paper on violent 8 aggressive behavior, have you done any other work 9 on Fluoxetine regarding violent aggressive 10 behavior, homicidality, hostility, aggression, 11 anything of that nature? 12 A. Aside from signing adverse drug 13 event reports, I do not recall. 14 Q. Do you recall signing adverse 15 drug event reports related to hostility, 16 homicidality, aggression, aggressive behavior? 17 A. Sure, I recall signing adverse 18 drug event reports that had those event terms 19 listed. 20 Q. On how many occasions? 21 A. It was part of my job over the 22 period of a year and a half or so, so on numerous 23 occasions. 24 Q. When was this part of your job? Page 78 1 A. During the time I was working 2 on Fluoxetine. 3 Q. Which was from when, refresh my 4 recollection, please? 5 A. I think around 1990 up through 6 the advisory committee meeting in September, 7 1991. 8 Q. Okay. 9 A. Thereabouts. 10 Q. Was it at the beginning of 11 1990? 12 A. I don't recall the exact time. 13 Q. Do you recall what time of 14 year? 15 A. I assume it was in the first 16 half of the year, but I don't recall exactly. 17 Q. Okay. When you say numerous 18 times, what do you mean by numerous times? 19 A. Adverse drug event reports need 20 to be signed off every day, and I could have 21 signed such reports every day. 22 Q. You could have signed violent 23 aggressive behavior related reports every day, 24 it's possible? Page 79 1 A. It's possible. 2 Q. There were that many of them? 3 MR. MYERS: That many violent 4 aggressive or that many reports? 5 MS. ZETTLER: That many violent 6 aggressive reports. 7 A. I don't know how many violent 8 aggressive reports there were. 9 Q. You said numerous, and you said 10 you could have signed them almost every day. I'm 11 trying to get an idea of how many is numerous, 12 one a day for a year and a half? 13 A. I don't know how many, and I 14 did not sign them necessarily every day because 15 we would rotate them amongst ourselves, amongst 16 the different physicians. So I may have signed 17 adverse drug event reports once a week or maybe 18 every day of the week depending on which other 19 physicians were in the group at the time. 20 Q. I just want to concentrate on 21 violent aggressive behavior related adverse 22 events and the post-marketing spontaneous reports 23 that you signed off on. 24 A. Okay. Page 80 1 Q. Give me an estimate over the 2 year and a half that you were signing adverse 3 event reports on how many violent aggressive 4 behavior adverse event reports that you signed 5 off on? 6 A. I do not know. 7 Q. More than a hundred? 8 A. I do not know. 9 Q. Less than a hundred? 10 A. I do not know. 11 Q. More than ten? 12 A. I do not know. 13 Q. Numerous regardless? 14 A. I remember signing off on some. 15 However many I signed off on, I do not know. 16 Q. Did it seem like a fairly 17 routine thing? 18 A. Signing adverse drug event 19 reports was a routine thing. Specifically for 20 hostility or violence, I do not know how many 21 there were. 22 Q. Did it seem like a fairly 23 routine thing for you to sign off on hostility or 24 violent aggressive behavior related adverse event Page 81 1 reports? 2 A. Since my job was routine to 3 sign off on adverse drug event reports, and if 4 hostility events were part of those reports, then 5 yes, it would be routine. 6 Q. See, Doctor, we've gone from 7 you testifying that you signed off on numerous 8 violent aggressive adverse event reports, related 9 adverse event reports, to not knowing how many 10 there are to -- I'm trying to get an idea of what 11 your definition of numerous is. Why don't I just 12 ask it that way, what is your definition of 13 numerous? 14 A. Maybe I misspoke. More than 15 one. 16 Q. Numerous is more than one? 17 A. Yes. 18 Q. Did you ever find yourself in a 19 situation where you were signing adverse event 20 reports -- you would review them all, right, you 21 would look them over, wouldn't you? 22 A. You mean the adverse event 23 reports? 24 Q. Right. Page 82 1 A. Yes. 2 Q. You would look them over very 3 carefully, wouldn't you? 4 A. Yes. 5 Q. Did you ever find yourself in a 6 position where you were looking at an adverse 7 event report and you said oh my gosh, look, 8 here's a hostile person, here's a person that 9 became hostile on Fluoxetine or gosh, here's a 10 person that became violent aggressive on 11 Fluoxetine? In other words, was it a surprise 12 for you when one of those adverse event reports 13 came up? 14 A. I don't remember if I had a 15 surprise. 16 Q. So we're down to numerous is 17 more than one, right? 18 A. Given that you want a number, 19 yes, that's the best definition to use. 20 Q. So anything more than one in 21 your mind is considered numerous? 22 A. For this particular example. 23 Q. How about suicidality, is more 24 than one numerous in suicidality? Page 83 1 A. It's probably safe for me to 2 use the same definition, so, yes. 3 Q. What situations would you not 4 use the definition of more than one being the 5 most? 6 A. I do not know. 7 Q. We have to do it on a specific 8 basis? 9 A. Probably. 10 THE WITNESS: Can we take a break? 11 MS. ZETTLER: Sure. 12 (A SHORT RECESS WAS TAKEN.) 13 Q. You're a medical physician, 14 aren't you? 15 A. I'm a medical doctor, yes. 16 Q. Would you say that more than 17 one cold per year are numerous colds? 18 A. Being more than one, sure, it 19 would be numerous. 20 Q. Would you be concerned about a 21 patient that came to you and said Doctor, I've 22 had more than one cold this year? 23 A. It would depend on the 24 situation. Page 84 1 Q. Regular, everyday sneezing, 2 sniffling, coughing cold, would that concern you? 3 A. It would depend on whether or 4 not they had underlying immunodeficiencies or 5 other comorbidities. 6 Q. What if it's just your average 7 normal person? 8 A. Maybe not. 9 Q. Are you concerned by the 10 numerous adverse event reports that you signed 11 off on regarding violent aggressive behavior and 12 hostility regarding Fluoxetine use? 13 A. I would like to take a step 14 back to answer your question. 15 Q. Sure. 16 A. As part of my job, I was 17 responsible for signing adverse drug event 18 reports, not only for Fluoxetine but other drugs 19 as well, at different times at Lilly. And on any 20 one day, given that I was signing off on them on 21 that one day, I could have as few as no reports 22 or several reports, more than one report. And 23 the same with Fluoxetine, I could have as few as 24 no reports to one report to more than one report Page 85 1 on any given day. Some of them may have been 2 hostility, some may not have, I don't recall the 3 exact number I signed off on hostility, however I 4 do know that I signed off on at least one 5 hostility report. Because I don't know the 6 number, I think that's the best answer I can give 7 you. 8 Q. Okay. And you define or you 9 characterize signing off on more than one 10 hostility report as being signing off on numerous 11 reports of hostility? 12 A. I'm trying to reconstruct in my 13 mind if when you first asked me and I answered 14 you saying numerous reports, if I meant adverse 15 drug event reports in general or hostility 16 reports, and maybe that answer was tied to 17 adverse event reports in general in my mind, but 18 I'm thinking that maybe your question was such 19 that it was tied to hostility. I remember 20 signing off on at least one hostility report, and 21 more than that, but I don't know the number. 22 Q. Why is it that that one 23 hostility report sticks out in your mind? 24 A. Interestingly we used to take Page 86 1 reports from the newspaper that would talk in 2 general about, you know, the media attention that 3 was gotten. We would sign off on the 1639s from 4 the newspaper reports which were general 5 discussions about different cases without any 6 individual patient data, and that's what sticks 7 out in my mind from those reports. 8 Q. So this one report that you 9 recall signing off on was a media report, 1639? 10 A. Certainly that was one of the 11 different types of reports we would get, right. 12 Q. I'm talking again about 13 hostility and Fluoxetine, specifically. 14 A. Sure, I seem to recall signing 15 off on hostility from media reports, yes. 16 Q. More than one? 17 A. I think so, yes. 18 Q. Aside from media reports, do 19 you recall signing off on hositility 1639s 20 related to Fluoxetine? 21 A. I think so. 22 Q. Go back to my original 23 question. Did it concern you signing off on 24 these numerous hostility adverse event reports Page 87 1 related to Fluoxetine? 2 A. I took every adverse event 3 report seriously. My concern on media reports of 4 hostility, or any other event, focused on the 5 fact that we never had patient specific 6 information or any more information such as even 7 with whom to follow up to get more information. 8 Q. Okay. Let's get back to my 9 question. Did the number of adverse events that 10 you signed off on regarding hostility and the use 11 of Fluoxetine concern you? 12 A. Not that I recall. 13 Q. Why not? 14 A. I don't recall how many I 15 signed or how many there were. I know we did not 16 have denominator data so that we could not put 17 numbers of reports in perspective. 18 Q. What's denominator data? 19 A. Numbers of patients exposed for 20 the particular compound. 21 Q. That information was available 22 to Lilly, was it not? 23 A. The information used to 24 estimate denominator data was usually not very Page 88 1 accurate. 2 Q. Why not? 3 A. The information used typically 4 was numbers of prescriptions or manufacturing 5 units which provided an estimate of numbers of 6 patients exposed. It's a good estimate, but it's 7 not the same as counting each patient as an 8 individual. 9 Q. That's because just because a 10 prescription is written doesn't mean the patient 11 actually took the drug; correct? 12 A. That's partly it, plus one 13 patient can get more than one prescription, so 14 those factors need to be kept in mind. 15 Nonetheless, it can act as an estimate of numbers 16 of patients exposed. But still, that kind of 17 information, accurate information, was lacking. 18 Q. So when Lilly says that the 19 number of people committing suicide on Fluoxetine 20 is small compared to the number of people 21 prescribed Fluoxetine, and they set out a 22 specific number or estimated number -- 23 A. Estimated number. 24 Q. -- like ten million people. Page 89 1 A. Estimated number, right. 2 Q. That's not a very accurate 3 number, right? 4 A. It's not the same as counting 5 each person, but it can provide an estimate. 6 Q. What variables would you take 7 into consideration to make the best estimate of 8 the number of people who have been exposed to 9 Fluoxetine? 10 A. Could you restate your question 11 a little bit different? 12 Q. Sure. You set out a couple of 13 different variables that are used in trying to 14 establish an estimate of the number of people who 15 have been exposed to Fluoxetine, one of them 16 being the number of prescriptions written and the 17 manufacturer units, the manufacturer units sold; 18 correct? 19 A. That's correct. 20 Q. Okay. Now, if you took, say, 21 manufacturer units in and of itself, what other 22 questions would you ask or what other information 23 would you rely on to translate the manufacturer 24 units sold to the number of people who have been Page 90 1 exposed to Fluoxetine? 2 A. I wasn't involved in those 3 calculations, so I don't know. 4 Q. Would you agree with me that 5 just because somebody is prescribed Fluoxetine 6 does not necessarily mean that they would be able 7 to take the drug? 8 A. That's always a possibility. 9 Q. For instance, they may not be 10 able to afford to get the prescription filled? 11 A. There are always a number of 12 possibilities. 13 Q. They may be noncompliant? 14 A. That's always a possibility. 15 Q. They may have a bad experience 16 on the drug and stop taking the drug; correct? 17 A. That's one possibility, sure. 18 Q. The drug simply may not work 19 for them and they may stop taking the drug or the 20 doctor may have them stop taking the drug; 21 correct? 22 A. Again, another possibility. 23 Q. How do you find out the number 24 of prescriptions that have been written or Page 91 1 filled? 2 A. I have used those data before, 3 and the data we've used has come from a company 4 that supplies that kind of information. 5 Q. What company? 6 A. IMS. 7 Q. What does IMS stand for? 8 A. I do not know. 9 Q. Where are they located? 10 A. I do not know where their 11 headquarters are. I seem to recall calling 12 Philadelphia, but I'm not sure that's where they 13 are. 14 Q. What's IMS's function, what do 15 they do? 16 A. I don't know their main 17 function, but I do know I've referenced 18 prescription data from them. 19 Q. When you say -- what do you 20 mean when you say you referenced prescription 21 data? 22 A. Well, in the letter to the 23 American Journal of Public Health that we wrote, 24 we referenced the number of prescriptions for Page 92 1 Fluoxetine, and we got that information from IMS. 2 Q. How do they get their 3 information? 4 A. I don't know. I remember 5 reviewing that at the time, but I don't recall 6 how they do it. I think they have to -- I 7 presume they have a number of surveys they 8 conduct. 9 Q. Any other prescribing 10 information that you've gotten from IMS other 11 than the number of prescriptions related to 12 Fluoxetine? 13 A. None that I've obtained from 14 them. 15 Q. Where did you get your 16 information regarding the annual suicide rates in 17 the United States that was set out in the letter 18 to the editor? 19 A. Federal government 20 publications. 21 Q. Did you contact the CDC? 22 A. The data in that letter came 23 from federal publications which I presume got 24 their data from the CDC or part of their national Page 93 1 center for statistics. 2 Q. Did you contact personally the 3 CDC? 4 A. For those data, no, I got them 5 from the federal publications. 6 Q. Did you contact anybody at the 7 CDC to attempt to get that suicide rate data? 8 A. I did at one time, yes. 9 Q. Why didn't you use CDC data? 10 A. The CDC data I had gotten, I 11 believe, were similar numbers to what were in the 12 publications, but I wanted something to reference 13 so I used published data. 14 Q. Who is Patrick O'Carroll? 15 A. That name rings a bell. 16 Q. Do you know who he is? 17 A. Yes. 18 Q. Who is he? 19 A. At the time, he was an employee 20 of the Centers for Disease Control. 21 Q. What did he do there? 22 A. I do not know his specific job 23 functions at the Centers for Disease Control, but 24 I knew he was in an area that looked at or Page 94 1 monitored surveillance of suicide. 2 Q. How do you know Patrick 3 O'Carroll? 4 A. I used to work at the Centers 5 for Disease Control, so I know him from my 6 employment at the Centers for Disease Control. 7 Q. What did you do at the CDC? 8 A. I worked as an epidemic 9 intelligence service officer. 10 (PLAINTIFFS' EXHIBIT NO. 9 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. When you were at the CDC, did 14 you do any work regarding suicidality? 15 A. No. 16 Q. Did you do any work regarding 17 homicidality, violent aggressive behavior? 18 A. I was a co-author on a paper 19 looking at years of life loss due to homicide. 20 Q. Where was that paper published? 21 A. In a morbidity and mortality 22 weekly report. 23 Q. Anything else that you did at 24 the CDC related to violent aggressive behavior? Page 95 1 A. No. 2 Q. When was that paper published? 3 A. I would need to check my 4 curriculum vitae, but maybe 1989. It would not 5 have my name as an author, being a federal 6 employee I'm listed only as the division of field 7 services, Centers for Disease Control. 8 Q. Do you remember the title of 9 the paper? 10 A. I think it's Impact of Homicide 11 on Years of Potential Life Lost. I don't 12 remember the rest of the title, maybe something 13 like Detroit or Michigan, I don't remember 14 exactly the details of it. 15 Q. Was it a specific review of 16 incidence of homicidality in Detroit -- or I mean -- 17 A. I think it was in Michigan, but 18 it could have been targeted on Detroit, I don't 19 recall specifically. 20 Q. What was the conclusion of the 21 paper? 22 A. There's a large number of years 23 of potential life lost in males fifteen to 24 twenty-five years of age. I believe that's the Page 96 1 conclusion. I believe higher in blacks than 2 whites, males. I would have to check the age 3 categories to be sure, but that would be easy to 4 do by reading it. 5 Q. Did you ever use that paper in 6 your work at Lilly on Fluoxetine? 7 A. No. 8 Q. Did anybody at Lilly use your 9 paper or any of the studies done in the paper on 10 their work on Fluoxetine at Lilly? 11 A. Not that I'm aware of. 12 Q. Have you had a chance to review 13 Exhibit 9? 14 A. Yes. 15 Q. Does that refresh your 16 recollection as to why you used suicidality rates 17 published by other governmental entities other 18 than the CDC? 19 A. Well, the data are collected 20 from one source and published through, I believe, 21 the U.S. Public Health Service, and I used the 22 published data so that I could reference it. And 23 if anybody wanted to go back and check it, they 24 could find the reference. Page 97 1 Q. Were you able to get from 2 Mister O'Carroll or anybody else at the CDC 3 suicidality rates after 1987 -- I'm sorry, after 4 1988? 5 A. I don't think so. 6 Q. How about before 1988? 7 A. I would need to review the 8 paper, but it seems to me that we referenced 9 publications of the data for every year included 10 in the letter to the editor. 11 Q. What did you mean in the first 12 subparagraph where you said, "He said that we 13 have had trouble getting the suicide mortality 14 data before 1988 because it isn't published (at 15 least not readily available)"? 16 A. I believe I was in the process 17 of trying to find published suicide mortality 18 rate data, and in my quest I called him, but 19 subsequently, after continuing to dig, we found 20 what we found. 21 Q. Okay. What do you mean in the 22 third subparagraph where you say a suicide 23 cluster was investigated in New Mexico and 24 published in this week's issue of MMWR? Page 98 1 A. Apparently a study was 2 conducted in New Mexico and published in that 3 particular publication. 4 Q. Was that study -- when you say 5 a suicide cluster, was that study similar to the 6 homicide study that you worked on in Michigan? 7 A. I don't think so. 8 Q. What's the difference between a 9 suicide cluster and the study that you did on 10 homicide? 11 A. The study we did on homicide 12 was a description of the impact of homicide and 13 years of potential life lost. This study, I 14 don't remember the details of it, I can only 15 guess that it was a cluster of suicide that 16 occurred, and the state health department of New 17 Mexico investigated the cluster to see why it 18 existed. 19 (PLAINTIFFS' EXHIBIT NO. 10 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 Q. Is Exhibit 10 a copy of the 23 letter to the editor relating to suicide rates 24 that you talked about earlier? Page 99 1 A. Exhibit 10 is the letter to the 2 American Journal of Public Health editor on 3 trends in suicide rates since Fluoxetine 4 introduction that I referenced earlier, yes. 5 Q. In the second paragraph of the 6 article you say that from its introduction 7 through December, 1991 an estimated three point 8 seven million U.S. patients have been treated 9 with Fluoxetine; correct? 10 A. Correct. 11 Q. Where did you get that figure? 12 A. Based on the estimates provided 13 by Lilly. 14 Q. Do you know where they got that 15 information? 16 A. I do not know the exact 17 calculation of that number or that estimate. 18 Q. Are you satisfied that that 19 number is accurate? 20 A. As an estimate, yes. 21 Q. In the last full paragraph, you 22 state there were more than six million Fluoxetine 23 prescriptions dispensed in the United States in 24 1989. You mean 1989 alone or as of 1989? Page 100 1 A. The way it's written, it means 2 six million Fluoxetine prescriptions in 1989. 3 Q. So in 1989 alone, you're 4 asserting in this article that six million 5 prescriptions of Fluoxetine had been dispensed in 6 the United States; correct? 7 A. More than six million 8 Fluoxetine prescriptions had been dispensed in 9 the United States in 1989, based on the reference 10 I provide. 11 Q. Is that a national prescription 12 audit, IMS? 13 A. Yes. 14 Q. Earlier in the same article you 15 state that from the time the drug was first 16 marketed in January, 1988 through December of 17 1991, only three point seven million people had 18 been treated with Fluoxetine; correct? 19 A. Correct. 20 Q. What accounts for the 21 difference between the two numbers? 22 A. Part of the calculation must 23 presumably include more than one prescription in 24 one individual. Page 101 1 Q. Okay. Anything else? 2 A. It would probably be dependent 3 on the methods used to calculate the estimated 4 number by Lilly. Maybe other options would be 5 filling prescriptions, not taking them. I'm sure 6 there are probably data that have surveyed people 7 when they get prescriptions on do they take them, 8 do they fill their prescriptions, those sorts of 9 data which probably factor into a formula to 10 calculate an estimate. That's my presumption. 11 Q. Would one of those factors be 12 people who were on Fluoxetine but had not been 13 treated with it successfully? 14 MR. MYERS: For which number? 15 MS. ZETTLER: The difference between 16 the six million -- more than six million 17 prescriptions in 1991 alone -- or 1989 alone, and 18 the three point seven million people being 19 treated with Fluoxetine in January of 1988 20 through December of 1991. Are 21 A. First there are different time 22 periods, and that's the important point to note, 23 and when we were talking about this earlier, 24 that's important to point out. Assuming that Page 102 1 there was a higher number of prescriptions 2 written for patients in the U.S. between 1988 and 3 1991 -- I'm sorry, I got that confused. But 4 probably one of the factors certainly would be 5 just because a prescription is written, doesn't 6 mean patient will take it or fill it. So that 7 could be one factor, but there are other factors 8 as well that probably went into this calculation 9 of the estimated number. 10 Q. Why didn't you break down the 11 1989 number to number of people who were treated 12 with Fluoxetine as opposed to the number of 13 prescriptions dispensed? 14 A. Because the data that IMS 15 provides is prescription data. 16 Q. Given that you could estimate 17 the number of people that had been treated with 18 Fluoxetine from January of 1988 through December 19 of 1991, could you not have estimated the number 20 of people who had been treated with Fluoxetine in 21 1989 alone? 22 A. Given I don't know the details 23 of the calculation of estimated number of 24 patients treated, I do not know how to answer Page 103 1 your question. However, we provide the data that 2 we obtained on prescriptions dispensed. 3 Q. Did IMS America have 4 information on prescriptions dispensed on 5 Fluoxetine since its marketing in 1988? 6 A. Probably. 7 Q. How come you didn't use that 8 information in December, 1989? 9 A. I don't remember why. 10 Q. Did you use that six million 11 Fluoxetine prescriptions dispensed in the U.S. in 12 1989 figure because it sounded good? 13 A. I do not recall why we used 14 1989, except that maybe it was the last data 15 point for which we had data after Fluoxetine 16 introduction. I mean 1988 was when it was 17 introduced, and then 1989, I believe, was the 18 next data point that we had available to us. I 19 don't recall at the time -- 20 Q. From IMS? 21 A. Yes, from IMS. I don't recall 22 at the time if we had data from 1990 or 1991. So 23 that could have been why we chose it, but I don't 24 recall specifically why. Page 104 1 Q. Was this -- this was published 2 in September of 1992; correct? 3 A. Correct. 4 Q. So there was two years in 5 between 1989 and September of 1992, two full 6 years? 7 A. It was completed earlier than 8 September of '92. 9 Q. When was it completed? 10 A. I don't recall that, but I know 11 that it was submitted to the journal, the journal 12 sent it back with some editorial suggestions, and 13 then we made the changes and sent it in again 14 during that time. Months can pass, and I don't 15 recall exactly when we completed the analysis and 16 the write-up. So part of that time lag is due to 17 that factor. 18 Q. What editorial changes did the 19 publication have on the letter? 20 A. Gosh, I don't recall 21 specifically. It seemed to me one of the 22 reviewers suggested referencing the work the 23 National Institute of Mental Health was doing, 24 which we incorporated in, but that's the only Page 105 1 change I recall specifically, although I think 2 there were some other minor changes that we 3 incorporated. 4 Q. When you say that the National 5 Institute of Mental Health was doing, are you 6 talking about the depression awareness, 7 recognition and treatment program? 8 A. Yes. 9 Q. Are you aware that Lilly has, 10 in conjunction with the National Institute of 11 Mental Health and other mental health 12 organizations, put together a public awareness 13 campaign on depression? 14 A. You asked me that last time, 15 and at the time I wasn't, but now I am. 16 Q. Okay. How did you become aware 17 of it, because of the national depression 18 screening day a few weeks ago? 19 A. I don't remember how I became 20 aware of it in that time period, but I became 21 aware of it. I honestly don't recall how. 22 Q. What is your knowledge of the 23 depression program put on by Lilly in conjunction 24 with NIMH and other mental health associations? Page 106 1 MR. MYERS: I object to the form. Your 2 question assumes it was put on by Lilly, and I 3 think that's an erroneous assumption. 4 MS. ZETTLER: Gee, Larry, it's kind of 5 funny because you go to one of these depression 6 screening days and you get all kinds of 7 propaganda from Lilly including questionnaires 8 that have the big Lilly logo on the bottom and 9 things like that. 10 MR. MYERS: I object to the form. 11 MS. ZETTLER: I believe their movie 12 says something about it, too. 13 A. I do not know much about the 14 program besides that there is a program. I do 15 not know what is part of the program, I don't 16 think I have seen it unless in some of the 17 circulators that come through my in box had 18 something on it. 19 Q. What is it that you now know 20 about the program? 21 A. Just what I told you. 22 Q. Which was -- I don't know if 23 you told me anything, frankly. 24 A. That -- well, I don't know any Page 107 1 real details, but I was under the assumption that 2 Lilly was somehow supportive of the National 3 Institute of Mental Health depression awareness, 4 recognition and treatment program, but that's 5 what I know. 6 Q. So you weren't aware that Lilly 7 was involved with that program when you wrote 8 this letter to the editor on trends in suicide 9 rates? 10 A. As I recall, I was unaware of 11 that. 12 Q. Why was this letter sent to the 13 editor? 14 A. To make people, health care 15 professionals, aware of this information. 16 Q. Is that Lilly's job? 17 A. Absolutely. 18 Q. Why? 19 A. We're involved in medical 20 research, and we're at the front lines of helping 21 to find diseases, interventions for diseases, and 22 it's very important to publish and get medical 23 information out to health care practitioners. 24 Q. Including medical information Page 108 1 on the suicidality rate related to the use of 2 your own products? 3 A. I'm not sure to which you 4 refer. Do you mean the meta-analysis article? 5 Q. No, I mean the actual number of 6 suicide attempts, suicidal ideation and suicides 7 that were experienced by patients on Fluoxetine 8 since the first day a patient even took 9 Fluoxetine back in the '70s or '80s. 10 A. Well, I don't know about that 11 particular example, but in general, we are 12 charged even with getting information out into 13 the medical literature on what we learn. 14 Q. To the medical literature to 15 the FDA? There's nothing that says that you have 16 to publish, is there? 17 A. Both the FDA and medical 18 literature. 19 Q. Is there a regulation that 20 dictates that Eli Lilly must publish results of 21 studies that it's conducting? 22 A. Not that I'm aware of. 23 Q. Is there a regulation that 24 dictates that Lilly must publish the incidence Page 109 1 rates of suicide, suicidality, homicide, violent 2 aggressive behavior, adverse events regarding 3 their use of the drug Fluoxetine? 4 MR. MYERS: When you say publish, you 5 mean like in a journal? 6 MS. ZETTLER: Right. 7 A. Not that I'm aware of. 8 Q. What do you mean when you say 9 that it's your responsibility that you should or 10 you must publish? 11 A. First of all, my job evaluation 12 is based on my publications. Secondly, my 13 background is in science, and one of my goals and 14 the company's goals is to have scientific 15 information published. 16 Q. Anything else? 17 A. I think that covers it. 18 Q. So what do you mean when you 19 say your job evaluation is based on publications? 20 A. Part of my performance is based 21 on the number of publications. 22 Q. Do you have a minimum limited 23 number of publications that you must publish 24 within a given -- or articles that you must Page 110 1 publish within a given period of time? 2 A. There's no defined number. 3 Q. Is there an inferred number? 4 A. There's no inferred number that 5 I'm aware of either. 6 Q. How many publications do you 7 publish a year or how many articles do you 8 publish a year? 9 A. If you include letters to the 10 editor, articles and abstracts, one to two a 11 year. 12 Q. Is that across the board for 13 all drugs that you work on for Lilly or is that 14 just related to Fluoxetine? 15 A. All projects. 16 Q. Have you ever been told by 17 anybody at Lilly that you needed to publish an 18 article, letter or abstract or otherwise on 19 Fluoxetine? 20 A. No. 21 Q. Do you feel that Lilly has 22 responsibility to inform the public if it has 23 information that comes to show that there is a 24 higher incidence of suicidality with the use of Page 111 1 Fluoxetine as compared to other antidepressants? 2 MR. MYERS: Before he answers, let me 3 object to the form only the extent that may get 4 into the question of legal responsibility to warn 5 under the intermediary rule, and I object to the 6 form on that basis. 7 Q. I'm asking you as a doctor and 8 a professional and somebody who has worked for 9 Eli Lilly. 10 A. Could you repeat the question? 11 Q. Sure. Do you think that Lilly 12 has a responsibility to inform the public if it 13 has information that tends to show that there is 14 an increased rate of suicidality related to the 15 use of Fluoxetine as compared to other 16 antidepressants? 17 MR. MYERS: Same objection. Answer if 18 you can, Doctor. 19 A. In my opinion, I believe we 20 need to make scientific information available to 21 the public. 22 Q. So the answer is yes? 23 A. Yes, the way I stated it, yes. 24 Q. The same would hold true for Page 112 1 violent aggressive behavior related to the use of 2 Fluoxetine? 3 MR. MYERS: Same objection. 4 A. Again, in my opinion, given 5 that a study is done appropriately and there are 6 no problems with it, then an attempt should be 7 made to publish an article. Just because an 8 attempt is made, does not necessarily mean a 9 journal will accept it for publication. 10 Q. Sure. In fact that happened on 11 one occasion with Doctor Beasley's meta-analysis 12 article, did it not? 13 A. I think so. 14 Q. It was submitted to the New 15 England Journal of Medicine and they rejected it; 16 correct? 17 A. I believe that's correct. 18 Q. Do you know why they rejected 19 it? 20 A. I do not know why. 21 Q. Do you know who would know why, 22 besides Doctor Beasley? 23 A. Besides Doctor Beasley, I do 24 not know. Page 113 1 (A SHORT RECESS WAS TAKEN.) 2 (PLAINTIFFS' EXHIBIT NO. 11 WAS 3 MARKED FOR IDENTIFICATION AND 4 RECEIVED IN EVIDENCE.) 5 Q. Okay. Doctor, have you had a 6 chance to look at Exhibit 11? 7 A. Yes. 8 Q. Does this refresh your 9 recollection as to your participation with 10 regards to the rechallenge protocol? 11 A. Regarding Exhibit 11, I recall 12 contributing the epidemiological perspective in 13 the text. 14 Q. Look at the first page of the 15 exhibit, please, and it appears to be a cover 16 page to the remainder of the exhibit; correct? 17 A. The first page is a cover page 18 to the remainder of the exhibit presumably, so, 19 yes. 20 Q. And you and Doctor Beasley are 21 listed together on the signature line of that 22 cover page; correct? 23 A. Yes. 24 Q. And it's your recollection that Page 114 1 the only thing you contributed to this approach 2 to study of potential association of suicidality 3 to antidepressant therapy is the epidemiology 4 section on the second page of the exhibit? 5 A. That's right. I spent a lot of 6 time thinking through the epidemiological 7 approaches and provided a summary on that. 8 Q. And you also testified earlier 9 that you were involved in the development of the 10 suicidality scale with Doctor Miller; correct? 11 A. I was involved in the initial 12 phases of discussions with Doctor Miller and 13 revising the MSSIR scale, that's right. 14 Q. Okay. Why is it that Lilly 15 wanted to use a revised form of the MSSIR instead 16 of using the MSSIR as it existed? 17 A. I don't remember the changes 18 that were going to be made to the MSSI 19 questionnaire, I don't remember what the 20 revisions were that were more specific than what 21 already existed. 22 Q. More specific to what? 23 A. To the measurement of suicide -- 24 or suicidal ideation, I believe is what it was. Page 115 1 Q. Did you review other 2 suicidality scales that existed prior to the 3 revision of Doctor Miller's scale? 4 A. I do not recall reviewing any 5 other suicide scales. 6 Q. Okay. How about anybody at 7 Lilly that you're aware of? 8 A. By your question, do you mean 9 did anyone else at Lilly review scales other than 10 the MSSIR scale, I do not know. 11 Q. Right. Are you aware that 12 there are a number of existing suicidality scales 13 that are used within the industry, psychiatric 14 industry? 15 A. I don't know how many scales 16 there are. 17 Q. If they're going to do a 18 rechallenge study of suicidality in people on 19 Fluoxetine, why would you not use the Hamilton 20 depression rating scale, question three as the 21 sole indicator of suicidality as what was looked 22 at in Doctor Beasley's meta-analysis article? 23 MR. MYERS: I object to the form only 24 to the extent that Doctor Beasley's meta-analysis Page 116 1 was a meta-analysis and not a rechallenge. 2 Q. Right, but the prominent 3 determinator of suicidality as looked at in 4 Doctor Beasley's article was HAM-D three, and 5 what I'm asking him is why if you're going to do 6 a rechallenge did you not choose to use just the 7 HAM-D three as was used in the clinical trials or 8 the MADRS? 9 A. I don't know an answer to your 10 question. 11 Q. Do you feel that the Hamilton 12 depression rating scale question three is a valid 13 indicator of suicidality in and of itself? 14 A. In my opinion, I believe it's a 15 good indicator of suicidality. 16 Q. Do you believe that one 17 question on a depression scale is a valid 18 determination of suicidality compared to scales 19 such as the MSSIR? 20 A. It's hard for me to give you a 21 comparison without remembering the MSSIR scale. 22 (PLAINTIFFS' EXHIBIT NO. 12 WAS 23 MARKED FOR IDENTIFICATION AND 24 RECEIVED IN EVIDENCE.) Page 117 1 MS. ZETTLER: Could you repeat back the 2 last question? 3 (THE COURT REPORTER READ BACK THE 4 REQUESTED TESTIMONY.) 5 Q. Do you believe that the 6 Hamilton depression rating scale question three 7 on suicidality in and of itself is as valid an 8 indicator of suicidality as the MSSIR? 9 A. Not knowing any validity data 10 comparing the two instruments, it's difficult to 11 answer, although I think the HAM-D three question 12 is a valid question to assess suicidal ideation. 13 Q. Do you believe one question in 14 and of itself, on a depression rating scale, 15 which focuses more on depression itself as a 16 whole as opposed to any given subsymptom of 17 depression, is as good an indicator of suicidal 18 ideation as a twenty-six or twenty-seven question 19 scale specifically designed to rate suicidality, 20 is that what you're saying? 21 MR. MYERS: Before he answers, let me 22 object to the form to the extent that your 23 question goes a step further and you've tried to 24 somehow characterize the scales as to what they Page 118 1 do or don't do. But if you can answer it go 2 ahead, Doctor. 3 A. There's a lot of debate in 4 survey literature about how many items should be 5 in questionnaires and what's more valid than 6 others. In my opinion, I believe the HAM-D three 7 question was a valid question. How its validity 8 relates or compares to the validity of the MSSIR, 9 I don't know because I haven't seen any 10 comparison of validity data. But taking the 11 HAM-D three question alone, I think it's a valid 12 approach in my opinion. 13 Q. So the answer to my question is 14 yes, you believe that item three on the HAM-D, in 15 and of itself, is as good an indicator of 16 suicidality as the twenty-six question 17 suicidality scale such as the MSSIR? 18 A. Like I said, I think it's 19 debatable, but in my opinion, yes. 20 Q. Debatable in what way? 21 A. Getting back to what I said 22 about the whole field of survey methodology and 23 how many items does it take to answer a question, 24 I mean that's a whole debatable issue. Page 119 1 Q. What's the HAM-D three S? 2 A. I need to review it to say 3 exactly what it asks. 4 Q. Does it ask if the person has 5 prepared to attempt to kill themself? 6 A. I need to review it in order to 7 answer your question. 8 Q. Does it ask whether or not a 9 person has talked or written about suicide? 10 A. Again, I would need to read the 11 particular question to be able to answer it. 12 Q. Do you recall whether or not 13 it's a multi-part question or it's a single 14 question? 15 A. It's a single item. 16 Q. Do you recall if it's a 17 multi-part question or a single question? 18 A. It's a single item requiring 19 judgment on the part of the person completing 20 that questionnaire or assessment. 21 Q. Doctor, do you remember if it's 22 one question or a number of different questions? 23 MR. MYERS: He's answered the question. 24 MS. ZETTLER: No, he hasn't, Larry. Page 120 1 Q. One simple question, yes or no, 2 do you remember whether it's one question or more 3 than one question? 4 MR. MYERS: You're not required to 5 answer yes or no, Doctor, that's not a 6 requirement. 7 A. I believe I've answered the 8 question. 9 Q. No, you haven't, and I'll ask 10 it again. You say it's a single item, it's a 11 suicide item, okay. But within that item, is 12 there one question or more than one question? 13 MR. MYERS: The scale speaks for 14 itself, it says what it says. 15 MS. ZETTLER: He's rendering an opinion 16 on a question that he doesn't even recall what it 17 asks. 18 MR. MYERS: Show it to him. 19 MS. ZETTLER: I'm trying to find out 20 what it is about the question and what he 21 remembers about the qeustion. 22 A. I could answer your question 23 much better if you could show me the HAM-D. 24 Q. I'm asking what your memory is Page 121 1 at this point. 2 MR. MYERS: Tell her what you recall. 3 A. I recall that the HAM-D has an 4 assessment made of each of the items on the 5 HAM-D, including item three which is a single 6 item. But there is an assessment made by the 7 person who fills it out, such as the physician or 8 health care professional, of a patient's 9 suicidality based on an interaction they have 10 with the patient. So the individual filling it 11 out may ask a series of questions to assess it, 12 and that's my understanding of the HAM-D. But 13 without rereading the instructions on it, it's 14 hard for me to answer your question. 15 Q. You can't look at a specific 16 clinical report form and tell from that clinical 17 report form if the investigator or the person 18 administering the HAM-D asks a series of 19 questions or simply gone through the questions 20 asked on the HAM-D, can you? 21 MR. MYERS: I object to the form, I 22 mean there are all sorts of clinical report forms 23 in clinical trials. 24 MS. ZETTLER: If there's one he can Page 122 1 tell me, he can tell me that. 2 A. I could probably answer your 3 question better by reviewing the HAM-D and its 4 instructions. 5 Q. What is your recollection? 6 A. My recollection is what I told 7 you. 8 Q. I know and my question is: Can 9 you look at a particular case report form, the 10 section regarding the Hamilton depression rating 11 scale, and tell from that case report form 12 whether or not the person administering the scale 13 to the patient has asked questions regarding 14 suicidality other than the ones that are listed 15 in the Hamilton depression rating scale or any 16 other element of the Hamilton depression rating 17 scale? 18 A. Not that I can recall without 19 reviewing the HAM-D. 20 Q. Okay. The Hamilton depression 21 rating scale item three was the focus of the 22 reanalysis of suicidality in clinical trials 23 performed on Fluoxetine for depression, was it 24 not? Page 123 1 MR. MYERS: I object to the form, 2 that's an erroneous assumption. Tell her if you 3 know. 4 A. I do not recall if it was the 5 primary focus. 6 Q. It was a focus, though, was it 7 not? 8 A. I believe it was one of the 9 outcomes that was studied. 10 Q. And the total Hamilton 11 depression scale score was also taken into 12 consideration; correct? 13 A. Again, I would need to review 14 the analysis and the paper to answer accurately. 15 I believe so, but without reviewing it, I can 16 give you my best guess. 17 Q. What is the purpose of 18 administering the Hamilton depression rating 19 scale, what are you looking for when you 20 administrator that scale? 21 A. In the clinical trials, I do 22 not know if the Hamilton depression rating scale 23 was required for depression studies. However, if 24 a physician uses the Hamilton depression rating Page 124 1 scale, they tend to use it as a tool, as an aid 2 in their diagnosis of depression of a patient. 3 Q. It measures the severity of 4 depression as a whole, does it not? 5 A. As a tool, I believe you're 6 correct. 7 Q. Okay. It's not specifically 8 designed to rate suicidality as its primary 9 purpose, is it? 10 A. The Hamilton depression rating 11 scale collects information on the components of 12 the disease depression. One of these components 13 is suicide, so it does collect that type of 14 information. 15 Q. That's not my question. My 16 question is: Is the primary purpose of the 17 Hamilton depression rating scale to rate 18 suicidality? 19 A. I do not know if that's the 20 primary purpose of the Hamilton depression rating 21 scale. 22 Q. Well, it's sure not the 23 Hamilton suicidality rating scale, is it? 24 MR. MYERS: Are you asking if that's Page 125 1 not what it's called? 2 MS. ZETTLER: Right. 3 A. Correct, it's not called that. 4 MR. MYERS: I'm glad we established 5 that. 6 MS. ZETTLER: I figured I would clear 7 it up for you, Larry. 8 (PLAINTIFFS' EXHIBIT NO. 13 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. Have you had a chance to read 12 Exhibit 12? 13 A. It's Exhibit 13, yes. 14 Q. I'm sorry. Does this refresh 15 your recollection regarding the meeting on 16 September 25, 1990 between Lilly employees and 17 the FDA? 18 A. A little better, yes. 19 Q. What do you remember now that 20 you look at this exhibit? 21 A. My main recollection is a 22 presentation made by Leigh of our clinical trial 23 data as is mentioned in this memo. 24 Q. What do you recall about that Page 126 1 presentation? 2 A. I don't recall any of the 3 specific data presented, but I remember that 4 suicide as the safety topic was discussed in fair 5 detail. 6 Q. How was the data for the 7 presentation accumulated, was it a computer 8 review of all clinical trials performed on 9 Fluoxetine to date? 10 MR. MYERS: What do you mean by a 11 computer review? 12 Q. I'm trying to figure out how 13 the data was accumulated within a nine month 14 period. 15 A. I believe whatever report was 16 submitted to the FDA in advance, as I recall, I 17 seem to recall that those data were presented at 18 this FDA meeting. 19 Q. What was submitted to the FDA 20 in advance? 21 A. I believe so, yes. 22 Q. What was? 23 A. Well, there was -- I believe 24 there was a summary report of the data analyzed Page 127 1 up to that time. 2 Q. What data was analyzed? 3 A. I think it was part of this 4 clinical trial meta-analysis, but I don't know at 5 what stage the analyses were at when they were 6 presented. 7 Q. What types of clinical trials 8 were analyzed, in other words double-blind 9 controlled studies only, single-blind studies? 10 A. We went over this last time, 11 and without reviewing the report, the paper and 12 things like that, I just can't recall what 13 specific studies were selected for these 14 analyses. 15 Q. Was an epidemiology study -- 16 MR. MYERS: Was there one? 17 Q. Was there an epidemiological 18 study that was presented to the FDA on September 19 25, 1990? 20 A. None that I recall. 21 Q. Was the results of a 22 rechallenge study? 23 A. Not that I recall. 24 Q. Was it a result of a Page 128 1 prospective study? 2 MR. MYERS: When you say prospective, 3 studies that were ongoing or prospective studies 4 that had been performed? 5 A. Right, performed. 6 A. I believe they were the 7 analyses of the prospective clinical trial data. 8 Q. Was it clinical trials that 9 were set up specifically to study suicidality as 10 it applied to the use of Fluoxetine? 11 A. I believe they were the 12 clinical trials of safety and efficacy of 13 Fluoxetine and comparitors. 14 Q. The clinical trials that were 15 run in part in support of the NDA, right? 16 A. I think so. 17 Q. Towards the bottom of the page, 18 it says the firm contended that prospective 19 trials were hampered by their inability to reach 20 agreement with Doctor Teicher on operational 21 criteria for the phenomenon referred to in his 22 article. Do you recall discussion about 23 contacting Doctor Teicher to help with a 24 prospective study? Page 129 1 A. I don't recall that. 2 Q. Do you recall what Lilly did to 3 investigate the validity of Doctor Teicher's 4 article, if anything? 5 A. I do not know to what extent 6 investigations were undertaken. 7 Q. Are you aware that Doctor 8 Jonathan Cole, a co-author on Doctor Teicher's 9 article, was a clinical investigator for Lilly on 10 Fluoxetine? 11 A. I guess I don't know that 12 definitively. 13 Q. Were you involved in any 14 discussions with Doctor Teicher regarding his 15 cooperation on putting together a prospective 16 study to look at phenomenon as he described in 17 his article? 18 A. I was not. 19 Q. Do you know of anybody who was 20 involved in such discussions? 21 A. Although I'm not a hundred 22 percent sure, I thought that Charles Beasley was. 23 Q. What is typical depression? 24 It's under A on the page, Doctor, if you're Page 130 1 looking for a reference. 2 A. I presume typical depression is 3 a major depressive disorder. 4 Q. You're presuming now? 5 A. I'm presuming that. 6 Q. From what, based on what? 7 A. Compared to, for example, 8 atypical depression, if that's the categorization 9 being used, which may be, you know, a major 10 depressive disorder with additional features. 11 But I'm presuming it. Without reviewing the DSM 12 three, I have to presume it. 13 Q. Did Eli Lilly communicate to 14 the FDA that they were not going to perform the 15 rechallenge study to your knowledge? 16 A. I don't know. 17 Q. Have you ever heard of Gerald 18 Rosenbaum? 19 A. Yes. 20 Q. Who is Gerald Rosenbaum? 21 A. The Gerald Rosenbaum I'm 22 thinking of, I believe is a psychiatrist. 23 Q. Okay. How is it that you know 24 Doctor Rosenbaum? Page 131 1 A. I believe I've seen a 2 publication by Doctor Rosenbaum. 3 Q. Is Doctor Rosenbaum a 4 consultant on the rechallenge protocol? 5 A. I do not recall if he was. 6 Q. Did he work with Doctor Miller? 7 A. I do not know that. 8 Q. How about John Rush? 9 A. Lilly had several consultants 10 on depression and suicidality in general, I do 11 not recall if Doctor Rush was one of them on 12 rechallenge or one of them on suicidality. In 13 fact, I can't even recall with certainty if he 14 was consulted for this specific issue. 15 Q. When you differentiate between 16 rechallenge and suicidality, what is the 17 differentiation? 18 A. I was just using your 19 categories. Suicidality, when I refer to that, I 20 was thinking about descriptive epidemiology 21 incidence, natural history of depression, as 22 opposed to an actual study. That's how I 23 categorized it in my mind, and that's how I 24 thought you were thinking about it. Page 132 1 Q. You said history of depression 2 in descriptive epidemiological what? 3 A. I said the natural history of 4 depression. 5 Q. And what else? 6 A. Such as the descriptive 7 epidemiology of the disease, in other words 8 what's the incidence of it, what's the 9 prevalence, what's the course of the disease. 10 Q. So it's your testimony that 11 Lilly consulted with outside people regarding the 12 nature and progression of depression? 13 A. I recall hearing some 14 presentations of outside persons on discriptive 15 epidemiology in depression, yes. 16 Q. What's descriptive epidemiology 17 of depression, give me an example? 18 A. Descriptive epidemiology is 19 defining who gets the disease, when do they get 20 the disease, what are the factors associated with 21 the disease, hypothesis-generating questions. 22 Q. Was Doctor Jan Fawcett one of 23 the on-site consultants? 24 A. He could have been. Page 133 1 Q. When did you attend these 2 meetings where they spoke? 3 A. I attended the internal 4 meetings when these outside consultants would 5 come in, and they occurred during the time I 6 worked on Fluoxetine projects. 7 Q. Before or after January of 8 1990? 9 A. I think I didn't start working 10 on Fluoxetine until 1990, so presumably after 11 January of 1990. 12 Q. How many consultants did you 13 listen to at these meetings? 14 A. I don't know the exact number. 15 Less than ten, I believe, more than four. 16 Q. Did these lectures by the 17 outside consultants focus on suicidality at all? 18 A. Could you specify your question 19 more? 20 Q. Sure. Were the reasons that 21 these gentlemen and ladies were asked to come in 22 and speak to you at these internal meetings at 23 Lilly, was the reason because of Doctor Teicher's 24 article or the incidence of increased suicidality Page 134 1 with the use of Fluoxetine? 2 A. I don't know the stated reason 3 why these consultants visited. I believe in one 4 case several of them came in to provide feedback 5 on analysis of the clinical trial data on 6 suicidality. 7 Q. All clinical trial data or just 8 double-blind controlled studies? 9 A. Again, I don't know which 10 particular studies were discussed in those 11 meetings. 12 Q. Were these consultants from 13 outside the U.S. or were they U.S. consultants? 14 A. I recall that they were U.S. 15 consultants, although there may have been 16 consultants outside the U.S., I don't know for 17 sure. 18 Q. Are you aware that Lilly 19 employees approached foreign consultants to look 20 at the incidence of suicidality and the use of 21 Fluoxetine? 22 A. I do not recall specifically, 23 although I wouldn't be surprised if they did. 24 Q. Do you recall that Doctor Page 135 1 Wheadon made a trip over to Europe to meet with a 2 number of different consultants outside the 3 United States? 4 A. I seem to recall a trip Doctor 5 Wheadon made overseas, right. 6 Q. Do you recall whether or not 7 that trip was related to rechallenge? 8 A. I do not know if the trip was 9 specifically related to rechallenge. 10 Q. Since the time we met last, do 11 you recall why a rechallenge study was not 12 performed at Eli Lilly or on their behalf? 13 A. No, I do not. 14 Q. The last time we talked, you 15 testified that part of the problem with the 16 rechallenge was the considerations of putting 17 people who had been suicidal on a drug that may 18 or may not make them suicidal again; correct? 19 MR. MYERS: Where did he say that, 20 since you're being pretty specific? 21 MS. ZETTLER: Did you find it? 22 MR. MYERS: Okay. Look at sort of the 23 bottom of one thirty-nine going over to one 24 forty. Page 136 1 Q. I was just trying to make sure 2 I understood your testimony from last time that 3 one of the ethical issues that were taken into 4 consideration when discussing whether or not to 5 conduct the rechallenge study was the ethical 6 consideration of placing people who had been 7 suicidal before on a drug that may or may not 8 cause them to become suicidal again. 9 MR. MYERS: Was that an ethical issue? 10 MS. ZETTLER: Right. 11 A. As suicide is part of 12 depression, the concern I recall was not about 13 the compounds causing suicidality, but actually 14 designing a study to look at suicide occurring in 15 patients. I recall that was the essence of the 16 discussion. 17 Q. And the pool of people from 18 which you would draw to determine whether or not 19 Fluoxetine was causing suicidality in a certain 20 percentage of people would be people who became 21 suicidal while they were on Fluoxetine; correct? 22 I mean that's the whole purpose of a rechallenge, 23 is it not? 24 A. I need to go back to the Page 137 1 exhibit to take a look at the rechallenge 2 protocol. 3 Q. Sure, go ahead. 4 A. For the protocol outline, the 5 pool of patients would include people who 6 developed in the clinical opinion of the treating 7 psychiatrist substantial suicidal ideation during 8 treatment with either Fluoxetine and tricyclic 9 antidepressant or Maprotiline. 10 Q. So in addition to rechallenging 11 people who became suicidal on Fluoxetine, you 12 were rechallenging people who became suicidal on 13 other psychotropic medications, like other 14 antidepressants? 15 A. Correct. 16 Q. Catherine Mesner testified the 17 other day. Do you know who she is? 18 A. I know Catherine Mesner. 19 Q. Who is she? 20 A. She's a clinical research 21 administrator. I don't know what area she's in 22 now, but I know who she is, and at the time she 23 served as a clinical research administrator on 24 Fluoxetine projects. Page 138 1 Q. Did she work with you on 2 developing the MSSIR? 3 A. If she did, I don't recall it. 4 My involvement was in the very beginning, in 5 setting up communications with Doctor Ivan 6 Miller, and I don't recall working with her on 7 it. 8 Q. Was Doctor Miller's study to be 9 validated before it was used in rechallenge or 10 any other study at Lilly? 11 MR. MYERS: Was his study to be 12 validated? 13 MS. ZETTLER: I'm sorry, his scale. 14 A. I believe that if changes were 15 to have been made to his validated scale, to a 16 new revised version, I recall conversations about 17 undertaking validation of it. 18 Q. Did you work on a protocol or a 19 proposed protocol for a validation study 20 regarding Doctor Miller's scale? 21 A. I did not work on a proposal to 22 validate that scale that I recall. 23 Q. Pardon? 24 A. To the best of my recollection, Page 139 1 I did not work on that. 2 Q. To your knowledge, was there a 3 protocol developed or a validation study of 4 Doctor Miller's scale? 5 A. I don't know if a protocol was 6 developed. 7 Q. So the answer to my original 8 question, Doctor Miller's scale, if changes were 9 made to it was to be validated before it was used 10 in a rechallenge study or any other study at 11 Lilly? 12 A. Could you read back the 13 question, please, I'm sorry. 14 (THE COURT REPORTER READ BACK THE 15 REQUESTED TESTIMONY.) 16 A. I don't know if that was agreed 17 upon because I was not involved in those 18 conversations. 19 Q. Why weren't you involved past 20 putting in the information on the epidemiological 21 study in Exhibit 11? 22 MR. MYERS: Wait a minute, that's a 23 different question. That exhibit has to do with 24 rechallenge, you're talking about a protocol Page 140 1 validating the scale, they are two different 2 things. 3 Q. Were you involved in a 4 rechallenge protocol other than your 5 contributions to Exhibit 11? 6 A. I recall my contribution to 7 Exhibit 11 was the evaluation of epidemiological 8 approaches to the study of suicidality, and I 9 recall that Charles Beasley was primarily 10 responsible for the rechallenge component. My 11 involvement in the suicidality revised scale by 12 Doctor Ivan Miller was very initial in that I 13 helped set up the linkage with Doctor Miller and 14 was even involved in the very preliminary review 15 of the MSSIR, and then was not involved in it 16 further. 17 Q. Why not? 18 A. It wasn't my primary 19 responsibility. 20 Q. What was your primary 21 responsibility at that time? 22 A. I was working on some of these 23 other safety projects that we've been over. 24 Q. Like tardive dyskinesia? Page 141 1 A. Uh -- 2 Q. Movement disorders? 3 A. That was one of them. I don't 4 know if that was the specific one at the time, 5 but that certainly was one of them I was working 6 on. 7 Q. Any other involvement with the 8 MSSIR other than what we've already talked about? 9 A. No. 10 Q. Any other involvement with 11 rechallenge or the consideration of rechallenge 12 as a study other than what we've talked about? 13 A. No. 14 Q. How about assessment of 15 patients with psychobehavioral deterioration? 16 MR. MYERS: What about it? 17 Q. Were you involved in that at 18 all? 19 A. I don't recall if I was. 20 (PLAINTIFFS' EXHIBIT NO. 14 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 Q. Have you had a chance to review 24 Exhibit 14? Page 142 1 A. I've had a chance to review 2 Exhibit 14. 3 Q. Does that refresh your 4 recollection, first of all, regarding the study 5 itself? 6 A. I do not recall this. 7 Q. Did you work on this study at 8 all? 9 A. I don't recall working on it. 10 Q. Who is Douglas Cocks, 11 C-O-C-K-S? 12 A. I believe his title is 13 corporate economist, but he's an economist at 14 Lilly. 15 Q. And Mitchell Daniels? 16 A. I don't know Mitch's current 17 title now, although I believe he was the 18 vice-president of corporate affairs at Lilly. 19 Q. Did you ever report to Mister 20 Cocks or Mister Daniels regarding the letter to 21 the editor of the American Journal of Public 22 Health regarding suicide trends? 23 A. I may have. 24 Q. Did you report to either or one Page 143 1 of those gentlemen as part of your job with 2 regard to suicidality? 3 A. No, I did not report to them as 4 part of my job. If I shared something with them, 5 it would have been for information. 6 Q. How about Vaughn Bryson, who is 7 Mister Bryson? 8 A. What about Mister Bryson? 9 Q. Who is he? 10 A. He was the CEO of Lilly for a 11 period of time recently. 12 Q. He's not CEO any longer? 13 A. No. 14 Q. Did you ever discuss the issue 15 of suicidality with Mister Bryson? 16 A. I never did. 17 (PLAINTIFFS' EXHIBIT NO. 15 WAS 18 MARKED FOR IDENTIFICATION AND 19 RECEIVED IN EVIDENCE.) 20 Q. Do you recognize Exhibit 15, 21 Doctor? 22 A. My name is on one of the notes 23 here, and I don't recall it, but obviously I saw 24 it. Page 144 1 Q. Do you recall an analysis or a 2 review of CDC data on suicidality? 3 A. I believe this is referring to 4 the American Journal of Public Health letter to 5 the editor data. 6 Q. The data that was used in that 7 letter did not come directly to the CDC, did it? 8 A. It's all federal government 9 data. I believe it comes from the National 10 Centers for Health Statistics, which is part of 11 the CDC, if that helps clarify it for you. 12 Q. So if they say CDC in this 13 memo, they mean that data? 14 A. I believe so. 15 Q. And this memo states that the 16 best that can be done about that data as far as 17 drawing conclusions with regards to suicide rates 18 is that the suicide rate had not changed; 19 correct? 20 A. Well, that's what Doug Cocks 21 wrote. 22 Q. Do you disagree with Doug 23 Cocks' analysis of the data? 24 A. Can I look at my letter to the Page 145 1 editor again? 2 Q. Sure. 3 A. I believe in our letter to the 4 editor we stated the conclusion a little bit 5 differently, although -- 6 Q. In a letter to the editor, you 7 state that there has been a modest decline in the 8 number of suicide deaths in the first two years 9 since Fluoxetine has been marketed; correct? 10 A. Right. 11 Q. Is that the conclusion that 12 you're talking about? 13 A. I think the main conclusion 14 that we drew in our letter was that these 15 modality data do not support claims of increased 16 suicide risk subsequent to the marketing of 17 Fluoxetine in the United States. 18 Q. Where is that? 19 A. Second column, last sentence in 20 the next to the last paragraph. 21 Q. But the beginning of that 22 paragraph states that there has been a modest 23 decline in the number of suicide deaths in the 24 first two years since Fluoxetine has been Page 146 1 marketed; correct? 2 A. That's what it says. 3 Q. And according to Douglas Cocks, 4 at least his analysis of data does not show a 5 modest decline in the number of suicide deaths, 6 does it? 7 A. I don't know what data he's 8 referring to, specifically, he just says that 9 there's not been a change in the suicide rate 10 unadjusted and age adjusted for the years 1982 11 through 1988. 12 Q. You agreed a couple of minutes 13 ago that the CDC data that he was referring to in 14 this memo was the same data that you guys looked 15 at in preparation for submission to the letter to 16 the editor; correct? 17 A. Presumably. However we stated 18 what we saw in the data, which was a modest 19 decline. 20 Q. What is a modest decline, less 21 than one? 22 A. I believe the numbers speak for 23 themselves. If you look at the numbers of 24 suicide deaths in the United States reported in Page 147 1 the letter to the editor, you'll notice the 2 numbers reported for each year. 3 Q. Is there statistical 4 significance between those numbers? 5 A. We never tested it for 6 statistical significance. 7 Q. Why not? 8 A. There didn't seem to be a need 9 to do that. 10 Q. Do you know if Douglas Cocks 11 tested it for statistical significance? 12 A. I do not know if he did that. 13 Q. What does he mean when he says 14 adding the provisional unadjusted data for '89 15 and '90? 16 MR. MYERS: I object to the form. 17 You're asking Doctor Kotsanos to interpret what 18 Mister Cocks meant when he said something. If 19 you know, tell her. 20 A. I believe he's referring to the 21 mortality data which were unadjusted for age, 22 which were not complete data. There is a certain 23 time lag in the U.S. federal mortality data, and 24 they tend to report provisional or incomplete Page 148 1 data as they continue to collect these data from 2 states which tends to trickle in over time. 3 Q. Who was writing to Vaughn 4 Bryson, is that Mitchell Daniels? 5 A. Looks that way. 6 Q. And Mister Daniels is saying to 7 Mister Bryson that apparently you can't torture 8 any stronger conclusion out of the data than what 9 Douglas Cocks had concluded; correct? 10 A. He says we apparently can't 11 torture any stronger conclusion out of the data 12 than this. 13 Q. But you guys did that in effect 14 for submission of your letter to the editor; 15 correct? 16 MR. MYERS: Did what? 17 Q. You were able to torture a 18 stronger conclusion out of it than what Mister 19 Cocks had come up with. 20 MR. MYERS: I object to the form. 21 A. We did not torture a stronger 22 conclusion out of data, we presented the data as 23 the data stands. 24 Q. Did you have any responsibility Page 149 1 with regards to the review of suicidality related 2 adverse events that occurred in the clinical 3 trials? 4 A. I did not have primary 5 responsibility for adverse events in clinical 6 trials, although on occasion, and it could have 7 been rare occasion, when the physicians in that 8 division were not in the office, I may have 9 signed off on some of their clinical trial 10 adverse event reports. 11 Q. I'm talking about the rereview 12 of adverse events that had previously occurred in 13 clinical trials that were related to suicidal 14 ideation or violent aggressive behavior. Did you 15 have any responsibility with regards to the 16 rereview of any such adverse events? 17 MR. MYERS: Rereview? 18 MS. ZETTLER: Right. 19 A. Could you clarify what you mean 20 by rereview? 21 Q. What is your understanding of 22 how the clinical trial data was reviewed by 23 Doctor Beasley in preparation for his 24 meta-analysis article? Page 150 1 A. I would need to read the 2 methods section of the meta-analysis paper to be 3 able to answer exactly how we reviewed the events 4 that made it in the clinical trial. 5 Q. Were you involved in any way 6 with the rereview of suicidality related adverse 7 events occurring in clinical trials in 8 preparation for Doctor Beasley's article or in 9 preparation for the advisory committee meeting in 10 September, 1991? 11 A. I don't recall doing a rereview 12 of these events. 13 Q. Did you work with any outside 14 consultants who were asked to review specific 15 cases of suicidal ideation or suicidal -- suicide 16 related adverse events or violent aggressive 17 adverse events that had occurred in clinical 18 trials? 19 A. I lost my train of thought in 20 your question, if she could read it back to me, 21 that would be helpful. 22 (THE COURT REPORTER READ BACK THE 23 REQUESTED TESTIMONY.) 24 A. No, I do not recall Page 151 1 specifically working on those. 2 Q. Who is Patrick Keohane? 3 A. Patrick Keohane is a research 4 physician at Lilly who is a division director. 5 Q. What division? 6 A. I do not know the exact name of 7 his division, it's either endocrinology or 8 internal medicine. 9 Q. Did he ever work on Fluoxetine 10 to your knowledge? 11 A. I do not know if he had primary 12 responsibility for Fluoxetine. 13 Q. Did he have any secondary or 14 indirect responsibility for Fluoxetine? 15 A. I recall communicating with 16 Patrick, and he shared information on Fluoxetine 17 and adverse events from the UK, the United 18 Kingdom. 19 Q. Doctor Inman? 20 A. Doctor Inman, yes. 21 Q. And what was Doctor Keohane's 22 involvement with Doctor Inman? 23 A. I believe he was Doctor Inman's 24 contact for Lilly in the UK. Page 152 1 Q. And what was Doctor Inman doing 2 with regards to Fluoxetine? 3 A. Doctor Inman had a system 4 whereby he studied adverse events occurring in 5 patients exposed to new products for a defined 6 period of time or for a defined number of 7 patients. And he did this for most, if not all, 8 new compounds that came out on the market. 9 Q. What was the reason that he did 10 it, was it a business of his? 11 A. I don't know if it's called a 12 business, I don't know the reasons why he did it, 13 but he did it. 14 Q. Was his data available to the 15 public? 16 A. I believe people can purchase 17 his reports, anyone, I believe. So presumably, 18 yes. 19 Q. Was Doctor Inman asked to 20 review cases of suicide or suicidal ideation that 21 he found in his -- in the course of his 22 collection of adverse events on Fluoxetine? 23 A. Asked by whom? 24 Q. By Lilly. Page 153 1 A. I do not know if Lilly 2 specifically asked him to review cases. 3 (PLAINTIFFS' EXHIBIT NO. 16 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to look 7 at Exhibit 16? 8 A. Yes. 9 Q. Does this refresh your 10 recollection as to whether or not Doctor Inman 11 was asked by Lilly to review cases of suicide or 12 suicidality that he had reported on regarding 13 people using Fluoxetine? 14 A. It does not refresh my 15 recollection on whether or not we specifically 16 asked him to review cases of Fluoxetine. We may 17 have, but I don't know. 18 Q. Is this letter to Doctor 19 Keohane from Doctor Inman? 20 A. It doesn't say. 21 Q. It does say, but it's blacked 22 out. 23 A. I would presume so, but it 24 doesn't say. Page 154 1 Q. The letter does say who it's 2 from, it's just blacked out; correct? 3 A. Whoever signed the letter, it's 4 blacked out, correct. 5 Q. So you would be able to tell 6 from an unredacted or unblacked out copy of the 7 letter who wrote the letter; correct? 8 A. Right, if this letter came 9 without the blocked out area. 10 Q. Do you know why you're carbon 11 copied on this, Doctor Kotsanos? 12 A. I don't recall the specifics of 13 how I had established a relationship with Doctor 14 Inman. I believe it was a project even prior to 15 Fluoxetine, but I was a contact of his at Lilly 16 in the United States, and I presume being that 17 contact, he copied me. 18 Q. But you already testified that 19 you had had discussions with Doctor Keohane 20 regarding Doctor Inman's reports of adverse 21 events on Fluoxetine; correct? 22 A. That's right. 23 Q. Did you have responsibilities, 24 primary, secondary, direct or indirect related to Page 155 1 working with Doctor Inman or anybody else outside 2 the United States, either collecting or reviewing 3 or analyzing suicidal adverse events related to 4 Fluoxetine? 5 A. Other than Doctor Inman? 6 Q. Including Doctor Inman. 7 A. The only other -- besides 8 Doctor Inman, the only other person I can think 9 of is a person named Herschel Jick who used a 10 data base in the United Kingdom to do 11 epidemiological studies, although he's based in 12 the states. 13 Q. He's based in the United 14 States? 15 A. I believe so. 16 Q. What was his name again? 17 A. Herschel Jick. 18 Q. Can you spell the last name? 19 A. J-I-C-K. 20 Q. Was he a doctor? 21 A. I believe he's a medical 22 doctor, yes. 23 Q. And he lives here in the United 24 States? Page 156 1 A. I don't know where he lives. 2 He actually, I believe, has a residence in both 3 countries, I think, but I'm not sure. 4 Q. Where is he located here in the 5 United States? 6 A. At the time I used to 7 communicate with him, he was located in Boston. 8 Q. And what was the purpose for 9 your communications with Doctor Jick? 10 A. I believe Doctor Jick and his 11 group had proposed an epidemiological study of 12 suicidality. 13 Q. Did Lilly take him up on his 14 offer? 15 A. We did not, to the best of my 16 recollection. 17 Q. Did you have any other contact 18 with Doctor Jick? 19 A. Regarding Fluoxetine and 20 suicidality? 21 Q. Regarding Fluoxetine generally. 22 A. What type of contact are you 23 referring to? 24 Q. Did you talk to him, did you Page 157 1 write to him, did you send him a telegram, any 2 contact whatsoever? 3 A. I did respond to his study 4 proposal in writing, I believe. 5 Q. Okay. 6 A. I also saw him at the FDA 7 advisory committee meeting, I think he was in 8 attendance there. 9 Q. Did you talk to him at the 10 advisory committee meeting? 11 A. Briefly. 12 Q. What was the subject of the 13 conversation? 14 A. Just social pleasantries. 15 Q. You mentioned Doctor Jick's 16 name in response to my question about whether or 17 not you had contact with Doctor Inman or anyone 18 else outside the United States with regards to 19 suicidal ideation related adverse events and the 20 use of Fluoxetine. Was there some other reason 21 that you communicated with Doctor Jick? 22 A. It wasn't specifically suicidal 23 ideation adverse events, it was an 24 epidemiological suicidality proposal, study Page 158 1 proposal. 2 Q. Suicide in general, but not 3 suicide related specifically to Fluoxetine? 4 A. I think it was Fluoxetine and 5 other antidepressants. But I would need to 6 review his proposal before I could say with 7 accuracy. 8 Q. Besides Doctor Inman and Doctor 9 Jick, did you talk with anyone else outside of 10 Lilly regarding suicidal ideation and the use of 11 Fluoxetine? 12 A. I do not recall if I had 13 contact with others, I may have, but I do not 14 recall right now. 15 Q. To your knowledge did Doctor 16 Inman review every suicidal act he reported 17 through his service regarding Fluoxetine? 18 A. Could you please specify what 19 you mean by review? 20 Q. Assuming that this is Doctor 21 Inman that's writing to Doctor Keohane in Exhibit 22 16, it appears to be a review of cases of suicide 23 committed by people who were on Fluoxetine; 24 correct? Page 159 1 A. This exhibit has two reports or 2 two patients who committed suicide in relation to 3 Fluoxetine therapy. 4 Q. And let me ask you this: Do 5 you know how many acts of suicide or suicidal 6 ideation were reported by Doctor Inman through 7 his service regarding Fluoxetine? 8 A. I do not recall the number, 9 although I think he enumerated it. 10 Q. What do mean by enumerated? 11 A. Provided the frequency data. 12 Q. Do you remember if it was more 13 than a hundred? 14 A. I do not recall. 15 Q. Do you know if Doctor Inman 16 reviewed each and every one of the cases that he 17 reported? 18 A. I do not know if he reviewed 19 each of the cases that he reported. 20 Q. Have you heard of a professor 21 Moller, M-O-L-L-E-R? 22 A. I don't recall that name. 23 Q. In Germany? 24 A. I don't know of a Doctor Page 160 1 Moller. I may have heard of his name, but it 2 doesn't ring a bell with me. 3 Q. How about Professor Ashcroft? 4 A. It seems I've heard that name, 5 I don't know why, when and where. 6 Q. Okay. How about Doctor Katona, 7 K-A-T-O-N-A? 8 A. I seem to recall hearing that 9 name as well, but again, why, when and where, I 10 do not know. 11 (PLAINTIFFS' EXHIBIT NO. 17 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Have you had a chance to review 15 the exhibit? 16 A. Yes. 17 Q. Do you recognize this exhibit? 18 A. I do not recall the exhibit, 19 although I'm on the address list, so presumably I 20 received it. 21 Q. Why would you be on the address 22 list? 23 A. Because of my involvement in 24 Fluoxetine projects. Page 161 1 Q. Fluoxetine suicide projects? 2 A. Considering the epidemiological 3 proposals, sure. 4 Q. So by virtue of your input in 5 the exhibit that -- Exhibit 11, talking about the 6 various possible trials that could be run to 7 study suicidality and the use of Fluoxetine, you 8 were copied on everything related to suicidal 9 ideation? 10 MR. MYERS: I object to the form, 11 that's not what he said. 12 MS. ZETTLER: I'm asking him. 13 MR. MYERS: You're asking him if he was 14 copied on everything related to suicidal 15 ideation. 16 A. I do not know if I was copied 17 on everything related to suicidal ideation, but 18 certainly I was copied on this. 19 Q. You were copied on a memo 20 written by Doctor Wheadon talking about contact 21 with foreign consultants to review suicidality 22 and the use of Fluoxetine; correct? 23 A. According to this exhibit, yes. 24 Q. You were copied on Exhibit 16 Page 162 1 which was a letter from Doctor Inman to doctor -- 2 a letter to Doctor Keohane from an outside 3 consultant reviewing suicidal ideation events; 4 correct? 5 A. I was copied on that Exhibit 6 16, yes -- well, given that that's Doctor Inman, 7 which presumably it is. 8 Q. Okay. You were involved in 9 rechallenge study meetings; correct, with the FDA 10 and in-house? 11 A. I was involved in certainly the 12 FDA meeting where the rechallenge study was 13 discussed. 14 Q. And I think you testified last 15 time that you did attend meetings at Lilly where 16 a rechallenge was discussed, did you not? 17 MR. MYERS: Show him where, if you're 18 going to refer to prior testimony. 19 Q. Did you attend meetings at 20 Lilly where the subject of suicidality and the 21 use of Fluoxetine was discussed, yes or no? 22 MR. MYERS: That's a different 23 question. 24 MS. ZETTLER: I'm asking him a new Page 163 1 question. 2 A. Yes, I attended meetings where 3 suicidality and Fluoxetine was discussed. 4 Q. Did you attend meetings where 5 rechallenge protocols were discussed? 6 A. I don't recall specific 7 meetings where I was an invited, aside from the 8 FDA meeting, to discuss rechallenge protocols. 9 It's possible, but I don't recall specifically. 10 (PLAINTIFFS' EXHIBIT NO. 18 WAS 11 MARKED FOR IDENTIFICATION AND 12 RECEIVED IN EVIDENCE.) 13 Q. Does this refresh your 14 recollection as to whether or not you were, first 15 of all, invited to attend a meeting where the 16 rechallenge protocol was discussed? 17 A. Per this memo, I certainly was 18 invited. I remember attending meetings when 19 Doctor Ivan Miller visited to talk about the 20 MSSIR revised, and it's possible I attended a 21 meeting on the rechallenge protocol, but as I was 22 not directly involved in that, I don't recall 23 specifically. 24 Q. Well, this exhibit indicates Page 164 1 that Doctor Miller, Doctor Rosenbaum and Doctor 2 Rush were also going to be participants in the 3 meeting regarding rechallenge, does it not? 4 A. That's correct. 5 Q. Do you recall if you attended 6 this meeting? 7 A. I don't recall if I attended 8 this meeting. 9 Q. Does it refresh your 10 recollection as to who Gerald Rosenbaum and John 11 Rush are? 12 A. Yes, I am aware of these 13 individuals, Doctor Rush and Doctor Rosenbaum. 14 Q. Does this refresh your 15 recollection as to whether or not Doctor Rush and 16 Doctor Rosenbaum were consultants on a 17 rechallenge protocol? 18 A. The memo does not specify if 19 they are outside consultants on the rechallenge 20 protocol, it just states they were outside 21 consultants, and I do not recall if they were 22 specifically outside consultants on rechallenge. 23 Q. Why would they be at the 24 rechallenge protocol meeting? Page 165 1 A. I don't know. 2 Q. Was it Lilly's policy to invite 3 outside consultants to meetings which are on 4 subjects that they would not be participating in? 5 A. I'm sure that the agenda was 6 defined for those individuals regarding their 7 attendance. 8 Q. That's not my question. My 9 question is: Is it Lilly's policy to invite 10 outside consultants or outside people to attend 11 meetings at Lilly regarding issues raised at 12 Lilly and by Lilly when they're not going to be 13 asked to participate in some manner in that 14 issue? 15 A. In my experience, no. 16 (PLAINTIFFS' EXHIBIT NO. 19 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 A. I have reviewed this Exhibit 20 19. 21 Q. Okay. Do you recognize the 22 exhibit? 23 A. It's a memo written by me. 24 Q. Who is Jana Hall? Page 166 1 A. Jana Hall is my secretary, was 2 my secretary. 3 Q. Point number three, it says 4 please see me about the approximately five 5 hundred spontaneous reports, we need to white out 6 the identifiers and the causality. What do you 7 mean by that, what five hundred spontaneous 8 reports are you talking about? 9 A. I think we're talking about 10 movement disorders of all types. 11 Q. Okay. And why would you need 12 to white out the identifiers and causality? 13 A. I believe that was part of our 14 process to have outside consultants review them, 15 so we removed personal identifiers and removed 16 any potential bias on them. 17 Q. So causality is a potential 18 bias? 19 A. Presumably in that case, it 20 was. 21 Q. Do you recall in approximately 22 five hundred spontaneous reports that you're 23 talking about in Exhibit 19 there being one 24 single case where it was determined by somebody Page 167 1 at Lilly that the movement disorder was in fact 2 causally related to the use of Fluoxetine? 3 MR. MYERS: I object to the form only 4 to the extent that you're assuming that the 5 decision was that it was in fact causally related 6 instead of one of these other definitions we've 7 been talking about, like reasonably, possibly 8 related or something like that. 9 Q. Do you understand my question, 10 Doctor? 11 A. I understand your question, but 12 I think to answer it -- I believe the reason for 13 the review of movement disorders was to have 14 outside consultants review the description of the 15 disorder and rate whether or not it was a 16 dyskinesia disorder or not. 17 Q. Then why was causality a 18 problem or why does it have to be blinded? 19 A. I believe we asked them to give 20 us their Gestalt upon review in all of the 21 events, and we didn't want to bias them with 22 anything that was completed by us. 23 Q. Go back to my original question 24 then. Do you recall, out of these five hundred Page 168 1 spontaneous reports related to movement 2 disorders, one report where it was noted on the 3 report that the adverse event related to the 4 movement disorder was causally related to the use 5 of Fluoxetine? 6 MR. MYERS: Same objection. Tell her. 7 A. I don't recall. 8 Q. You don't recall whether there 9 was one or not or you don't recall any causally 10 related movement disorders? 11 A. I don't recall. It's possible, 12 but I don't recall specifically, I would need to 13 review them again. 14 Q. Were all five hundred 15 spontaneous reports submitted to the consultants? 16 A. Yes. And that's an approximate 17 number. 18 Q. Okay. Approximately five 19 hundred. Who were those consultants? 20 A. Doctor Harold Klawans and 21 Doctor Bill Glaser. 22 Q. Doctor Klawans, is that at Rush 23 Presbyterian or at least he was at that time? 24 A. He was at that time. Page 169 1 Q. Where is Doctor Glaser from? 2 A. I believe at that time he was 3 from Yale. 4 Q. Do you know where he is now? 5 A. I don't know. 6 Q. Did Doctor Klawans and Doctor 7 Glaser in fact review those five hundred 8 spontaneous reports? 9 A. I believe they did. We asked 10 them to focus on certain ones, but I believe they 11 did. 12 Q. Which ones did you ask them to 13 focus on? 14 A. Dyskinesia reports. 15 Q. What's dyskinesia? 16 A. I'm sorry? 17 Q. What is dyskinesia? 18 A. Involuntary movements. 19 Q. Is that physiologically or 20 psychologically based involuntary movements? 21 A. In this case, it's 22 physiological. 23 Q. Did you contact Doctor Klawans' 24 employees at any time and tell them to cease Page 170 1 their review of the information you gave them on 2 movement disorders? 3 A. I don't recall doing that. 4 Q. Was there another review of 5 movement disorders that was done either in 6 conjunction, prior or after Doctor Klawans and 7 Doctor Glaser's review? 8 A. During my involvement, there 9 wasn't any that I was aware of. There may have 10 been prior to my involvement or even after my 11 involvement. 12 Q. Did you contact other 13 consultants besides Doctor Klawans and Doctor 14 Glaser to review the movement disorder adverse 15 events? 16 MR. MYERS: At the same time or -- 17 MS. ZETTLER: Yes, at the same time. 18 A. Yes, I did. 19 Q. Who else? 20 A. I believe I contacted Doctor 21 Jankovick, and I believe I contacted Doctor Fahn. 22 Q. Could you spell Jankovick? 23 A. I don't know if I'm spelling it 24 correctly, but I think it's J-A-N-K-O-V-I-C-K. Page 171 1 Q. What was the second one? 2 A. Fahn, Doctor Fahn. 3 Q. F-A-N? 4 A. F-A-H-N. 5 Q. Anybody else? 6 A. I think Doctor Meltser, but I'm 7 not positive about that. 8 Q. Is that Doctor Meltser who 9 conducted clinical trials for Lilly? 10 A. I think so. 11 Q. What is Doctor Jankovick's 12 first name? 13 A. I don't know that. 14 Q. How about Doctor Fahn? 15 A. I think it's Stanley. 16 Q. Do you know where Doctor 17 Jankovick was located when you contacted him to 18 be a consultant? 19 A. I think he was in Texas, but 20 I'm not a hundred percent certain. 21 Q. How about Doctor Fahn? 22 A. I don't remember. 23 Q. Did you ask any of these 24 gentlemen to sign a confidentiality agreement? Page 172 1 A. I may have, I don't recall. 2 Q. Did you submit this five 3 hundred -- these five hundred spontaneous reports 4 to Doctor Jankovick, Doctor Fahn or Doctor 5 Meltser? 6 A. Not that I recall, no. 7 Q. Was it your intention to have 8 five consultants review the five hundred 9 spontaneous reports? 10 A. No, that was not our intention. 11 Q. Why did you decide not to use 12 Doctor Jankovick, Doctor Fahn or Doctor Meltser? 13 A. Doctor Fahn, I believe, told me 14 he was going to be out of the country or out of 15 town and unavailable. Doctor Jankovick, I seem 16 to recall -- I think Doctor Jankovick was a 17 physician caring for a patient that was involved 18 in a lawsuit, so I believe we mutually agreed not 19 to work together. And I don't remember why we 20 didn't work with Doctor Meltser. 21 Q. When you say Doctor Jankovick 22 was involved in treating a patient who was 23 involved in a lawsuit, was that lawsuit related 24 to movement disorders and the use of Fluoxetine? Page 173 1 A. I think so, yes. 2 Q. Was the review of the five 3 hundred spontaneous reports done by Lilly in 4 response to lawsuits that were filed related to 5 movement disorders and the use of Fluoxetine? 6 A. I don't recall specifically if 7 that was the case. I seemed to remember that 8 there was a review of movement events undertaken 9 earlier by Charles Beasley, and one of the things 10 was to follow up on that review, and I don't 11 recall if a lawsuit had anything to do with that 12 or not or it was just part of our spontaneous 13 routine review. 14 Q. As part of your spontaneous 15 routine reviews, do you hire outside consultants 16 to review adverse event reports? 17 A. Sometimes. 18 Q. In what cases, what situations 19 would you do that? 20 A. To get a second opinion, so to 21 speak. 22 Q. I understand the purpose of why 23 you would want to do that, but I wanted to know 24 in what situations would Lilly feel compelled to Page 174 1 go to outside consultants to review their adverse 2 event reports? 3 MR. MYERS: I object to the form. He 4 didn't say they felt compelled to do anything, he 5 just gave an example why. You don't have to 6 agree with her terminology about being compelled, 7 Doctor. 8 A. On occasion, we believe it's 9 necessary to go outside for a second opinion, if 10 I can use that terminology, in terms of diagnosis 11 or evaluation of the events. 12 Q. Such as in a situation where a 13 lawsuit is filed? 14 MR. MYERS: I object to the form, 15 that's not what he said. 16 MS. ZETTLER: I'm asking him, I'm 17 giving him specific examples and he can tell me 18 if that's a situation or it's not. 19 MR. MYERS: Well, if he has worked with 20 an outside consultant in connection with any 21 lawsuit, he's not going to disclose that to you. 22 MS. ZETTLER: That's not what I'm 23 asking him. I'm asking him if that's one 24 situation where they would feel compelled to go Page 175 1 to outside consultants. 2 A. We don't necessarily feel 3 compelled to go to outside consultants for those 4 reasons. However, we could go to an outside 5 consultant for numerous reasons. 6 Q. Such as? 7 A. Where the diagnosis is unclear 8 of a certain disease. 9 Q. Okay. An increased frequency 10 of a certain event? 11 A. That's a possibility. 12 Q. An adverse event that was 13 unanticipated? 14 A. Again, that's another 15 possibility. 16 (PLAINTIFFS' EXHIBIT NO. 20 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 Q. Do you recall these letters, 20 Doctor, reflected in Exhibit 20? 21 A. I recall writing these letters. 22 Q. Who did you send these letters 23 to? 24 A. It could have been any one of Page 176 1 the three consultants we just talked about. 2 Q. What did you mean when you say 3 I wanted to confirm in writing that since we 4 changed our plans regarding the movement event 5 reports, we no longer need to pursue the letter 6 of confidentiality agreement dated August 16, 7 1990 which you had signed? 8 A. Just what it says, I guess. 9 They had signed a letter of confidentiality, and 10 we had changed our plans on pursuing that line of 11 work with them. 12 Q. Who changed their plans? When 13 you say we changed our plans, you mean Lilly 14 changed their plans? 15 MR. MYERS: I object to the form only 16 to the extent he told you why they did not pursue 17 those other three people, he already answered 18 that question. 19 A. Yes, I thought I did. 20 Q. I'm asking what the letter 21 means, you wrote it. 22 MR. MYERS: What the letter means is 23 another question. 24 MS. ZETTLER: That's what I'm asking Page 177 1 him, Larry. I'm asking him who changed their 2 plans as reflected in this letter, whose plans 3 were changed, was it Lilly's plans, the witness' 4 plans, the doctor's plans? That's what I'm 5 asking him, whose plans were changed. 6 MR. MYERS: I object to the form 7 because I believe he answered that in explaining 8 why they did not work with those other three 9 people. 10 A. Right. I believe the we, in 11 the sense we changed our plans, refers to Lilly, 12 if that's what you're asking. 13 Q. Does this refresh your 14 recollection as to why you didn't work with 15 Doctor Fahn or Doctor Meltser? 16 A. I explained Doctor Fahn's 17 situation, I explained Doctor Jankovick, and I 18 told you I couldn't recall specifically Doctor 19 Meltser. 20 Q. Okay. So Doctor Fahn, I 21 believe you stated, could not participate because 22 he was going to be out of the country; correct? 23 A. Or he was going to be 24 unavailable for a period of time, that's what he Page 178 1 told me. 2 Q. And Doctor Jankovick couldn't 3 participate because one of his patients was suing 4 Lilly because of a movement disorder related 5 adverse event? 6 A. I think that's the reason. 7 Q. You knew that before you asked 8 him to sign a confidentiality agreement, did you 9 not? 10 A. I did not, no. 11 Q. So for whatever reason, this is 12 just a form letter that you sent out to at least 13 two of the three doctors -- 14 A. That's right. 15 Q. -- memorializing that you 16 didn't want to work with them. 17 A. At least one of them. 18 Q. If you look at it, it looks 19 like two separate letters, does it not, two 20 separate addressees, at least? 21 A. If the two copies means that 22 there were two different addressees, then yes. 23 Q. And it could also -- we can't 24 tell from this letter if it's in fact Doctor Page 179 1 Jankovick, Doctor Fahn or Doctor Meltser or 2 Doctor Glaser or Doctor Klawans; right? 3 A. I don't think it's Doctor 4 Klawans or Doctor Glaser, but you're right about 5 the other three, we don't know. 6 Q. We can't tell if it is Doctor 7 Klawans or Doctor Glaser because the names are 8 blacked out on the the letter; right? 9 A. It's difficult to tell because 10 the names are blacked out. But I don't recall 11 writing one of these to Doctor Klawans or Doctor 12 Glaser. 13 Q. Do you recall writing these to 14 the other gentlemen? 15 A. I'm sorry, could you repeat 16 that? 17 Q. Sure. Do you recall writing 18 these letters to all three of the other doctors? 19 A. I don't know if I sent one to 20 all three of the doctors because I'm not sure we 21 signed a confidentiality with all three of them. 22 Q. Was there a protocol written 23 with regards to the review of the dyskinesia 24 adverse events, in other words was a protocol Page 180 1 written under which the review would be 2 undertaken? 3 MR. MYERS: For the thing he said 4 Klawans and Glaser did? 5 Q. For the entire project of 6 collecting, reviewing and analyzing movement 7 disorder adverse events. 8 A. There was not a protocol 9 written for our outside consultants, but I 10 believe there was a protocol written for internal 11 work. 12 Q. Okay. To your knowledge was a 13 protocol written related to Doctor Beasley's 14 meta-analysis of the clinical trial data base? 15 A. You mean the dyskinesia 16 protocol? 17 Q. No, his meta-analysis. Was 18 there a protocol written for Doctor Beasley's 19 meta-analysis related to suicidality? 20 A. I remember seeing Doctor 21 Beasley working on case definitions and other 22 details of the methods. My presumption is yes, 23 but I don't know for certain. Presumably, yes. 24 Q. Did you have to get approval Page 181 1 from the FDA to do the analysis of movement 2 disorders? 3 A. What do you mean by approval 4 from the FDA? 5 Q. Is it your understanding that 6 clinical trials that are going to be run under 7 the IND or NDA need approval by the FDA? 8 MR. MYERS: Wait a minute. Before he 9 answers, I object to the form to the extent that 10 I think you're assuming that was a, quote, 11 unquote, clinical trial. 12 MS. ZETTLER: I'm asking him as far as 13 clinical trials are concerned. 14 MR. MYERS: You're asking generally, a 15 general question? 16 MS. ZETTLER: Yes. 17 A. In general, to conduct a 18 clinical trial of investigation, yes. Regarding 19 the movement disorders or a routine safety 20 review, no, not this specific analyses we 21 undertook. 22 Q. Okay. What's an ANOVA 23 analysis, A-N-O-V-A? 24 A. I would need to refer you to a Page 182 1 statistician to answer that question. 2 Q. It's a statistical analysis? 3 A. That's right. 4 Q. Do you know if Doctor Klawans 5 is still at Rush Presbyterian in St. Louis? 6 A. I do not know if he is. 7 (PLAINTIFFS' EXHIBIT NO. 21 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Have you had a chance to look 11 at Exhibit 21? 12 A. Yes. 13 Q. Do you recognize this exhibit? 14 A. Yes. 15 Q. Can you tell me what it is? 16 A. It's a summary of adverse event 17 reports mentioning tardive dyskinesia or tardive 18 dystonia of the Lilly drug experience network 19 through March 28th, 1991. It's a proposal to 20 look at a review of the Prozac clinical trial 21 data base and protocol, and provides background 22 information on tardive dyskinesia and tardive 23 dystonia. 24 Q. Was there something similar to Page 183 1 this written up for the review and analysis of 2 adverse events related to movement disorders in 3 general? 4 A. I'm sorry, what do you mean by 5 movement events in general? 6 Q. Movement disorders in general. 7 MR. MYERS: Broader than tardive 8 dyskinesia and tardive dystonia? 9 Q. Right. Was there another 10 project that was done that related to movement 11 disorders in general as opposed to just tardive 12 dyskinesia and tardive dystonia? 13 A. Many. There's no other 14 document that I'm aware of that was written to 15 review movement events in general. 16 Q. Okay. But to your knowledge 17 was there another project done such as the one 18 reflected in Exhibit 21 where information on 19 movement disorders in general was collected, 20 reviewed and analyzed? 21 MR. MYERS: In addition to what he said 22 Doctor Klawans and Doctor Glaser did? 23 MS. ZETTLER: Yes. 24 MR. MYERS: You're not counting that or Page 184 1 are you counting that? 2 MS. ZETTLER: No, I'm counting that. 3 A. In addition to the review that 4 Doctor Klawans and Glaser did, the only other 5 review I'm aware of is the one Charles Beasley 6 undertook prior to our involvement. 7 Q. Review of movement disorders? 8 A. I believe so, I believe he 9 reviewed movement disorders that focused on 10 dyskinesia. 11 Q. How long before your 12 involvement with movement disorders did Doctor 13 Beasley do his analysis on movement disorders? 14 A. I don't know the exact time. 15 Q. I'm not asking for the exact 16 time, give me an estimation. 17 A. I would guess six months to a 18 year. 19 Q. Why was Doctor Beasley 20 analyzing tardive dyskinesia and tardive dystonia 21 and the use of Fluoxetine at that time? 22 MR. MYERS: I object to the form, 23 Nancy, only to the extent that I think Doctor 24 Kotsanos described movement disorders generally -- Page 185 1 MR. ZETTLER: Okay, movement disorders 2 generally. 3 MR. MYERS: -- and we said with a focus 4 on dyskinesia. 5 A. I do not know why he undertook 6 that review. And even though I reviewed this 7 document, it may be in here, but I don't recall 8 seeing it, I didn't read it that carefully. 9 Q. Were the twenty-three tardive 10 dyskinesia and tardive dystonia adverse events 11 that were submitted to Doctor Klawans and Glaser 12 separate and apart from the five hundred movement 13 disorder events that you talked about in Exhibit 14 19? 15 MR. MYERS: As opposed to a subset? 16 MS. ZETTLER: Right. 17 A. When we sent the movement 18 events to Doctor Klawans and Glaser, I believe we 19 categorized each of the events by its descriptive 20 term by which it was collected in the data base, 21 such as tremor or extrapyridimal syndrome or 22 dyskinesia. So we did break it down that way. 23 Q. So the answer to my question is 24 the twenty-three were included in the five Page 186 1 hundred? 2 A. Right, but all the five hundred 3 were categorized into their descriptive movement 4 event. 5 Q. Did Doctor Klawans and Glaser 6 do separate reports specific to tardive 7 dyskinesia and tardive dystonia? 8 A. I believe we asked them to 9 focus on those, and that was the basis of their 10 reports, although they were asked to review all 11 the events they received. 12 Q. Are you done? 13 A. I'm done. 14 Q. Could you turn to page Pz 2445 15 1025, the history. Do you know why tardive 16 dyskinesia was not an ELECT term prior to January 17 31, 1990? 18 A. I do not know why. 19 Q. Do you know why tardive 20 dystonia was not an ELECT term or and SSAI term 21 as of the writing of this history? 22 A. Again, I do not know why. 23 Q. To your knowledge did either 24 Doctor Glaser or Doctor Klawans find any cases of Page 187 1 tardive dyskinesia, tardive dystonia or movement 2 disorders in general that they felt were causally 3 related to the use of Fluoxetine? 4 A. My knowledge of their Gestalt 5 overall summary was that they did not. But 6 whether or not they indicated any specific case, 7 I do not recall, but the overall summary was no, 8 as I recall. 9 Q. The overall summary meaning 10 generally? 11 A. Taken as a whole. 12 Q. It was not related to 13 Fluoxetine? 14 A. That's right. Of course, it 15 would be helpful to review the reports. 16 Q. If you look at Pz 2445 1031. 17 A. Okay. 18 Q. Does this refresh your 19 recollection as to Doctor Glaser's and Doctor 20 Klawans' conclusions as a result of their review? 21 A. Somewhat. 22 Q. Okay. Tell me what refreshes 23 your recollection, what do you remember now? 24 A. It helps me with -- it helps me Page 188 1 confirm what I stated earlier, stated in this 2 memo, per Doctor Klawans, none of the reports 3 contained an update to show that Prozac is 4 pathogenic for tardive dyskinesia, but Prozac 5 appeared to worsen the symptoms in some patients. 6 And Doctor Glaser's summary was, based on his 7 rating system, nearly half the patients were 8 unlikely or definitely not due to Prozac, and the 9 remainder, there was no clear explanation for the 10 reports in relation to Fluoxetine therapy as some 11 did not have enough data to rate them. 12 Q. If either Doctor Glaser or 13 Doctor Klawans had indicated to you or somebody 14 else at Lilly that they felt that there were 15 specific cases of the twenty-three tardive 16 dyskinesia and tardive dystonia adverse events 17 that they reviewed that they felt were related to 18 Fluoxetine, should it have been included or 19 mentioned in that summary? 20 MR. MYERS: This page right here, is 21 that what you're talking about when you say this 22 summary? 23 MS. ZETTLER: Correct. 24 A. Are you talking about page Pz Page 189 1 2445 1031? 2 Q. Right, in the summary of the 3 reports -- 4 A. This summary page was not 5 written by Doctor Glaser or Klawans. 6 Q. Right. 7 A. It's just a condensation of 8 their reports. So I would need to review their 9 specific reports to answer your question. 10 Q. What I'm asking you is if they 11 had said, either one of them had said, to you, 12 Doctor Kotsanos, I believe that this case, this 13 case, this case, this case, et cetera, et cetera, 14 are related to the use of Fluoxetine, would that 15 have been specified in the summary or should it 16 have been specified in the summary? 17 A. I do not know if they specified 18 it in the summary. 19 Q. They didn't here, right, they 20 didn't mention any cases that the doctors felt 21 were related to the use of Fluoxetine, did they, 22 on this page, Pz 2445 1031? 23 A. Per this page, there doesn't 24 seem to be any specified. Page 190 1 Q. Did you work on the report sent 2 to the FDA as a result of Doctor Klawans or 3 Doctor Glaser's review of the tardive dyskinesia 4 cases? 5 A. I don't know if we sent a 6 report written by Lilly to the FDA, I thought we 7 just -- I believe we just sent the consultants' 8 reports to the FDA. 9 Q. Forwarded it on to the FDA? 10 A. Right. 11 MS. ZETTLER: Let's take a break. 12 (A SHORT RECESS WAS TAKEN.) 13 Q. Let's talk a little bit about 14 your signing off on 1639 reports. Do you still 15 do that? 16 A. No. 17 Q. When did your responsibilities 18 related to signing off on adverse event 1639 19 reports cease? 20 A. I do not know the exact time, 21 but I believe it was after the advisory committee 22 meeting in September of 1991, sometime after 23 that. 24 Q. I forgot what you said earlier. Page 191 1 You said that you did work as a clinical monitor 2 on Fluoxetine clinical trials? 3 A. No, I did not say that. 4 Q. Did you have responsibility for 5 reviewing any adverse events that occurred during 6 clinical trials on Fluoxetine? 7 A. Again, as I said earlier, the 8 only time I would have done that is if the 9 physicians responsible for that were not in the 10 office and I was the only one around, which would 11 have been on a rare occasion. As I recall, I 12 think most of my work on signing adverse event 13 reports was post-marketing event reports. 14 Q. Spontaneous adverse events? 15 A. That's right. 16 Q. I think earlier you said, when 17 we were talking about the number of hostility 18 related adverse events, that you had that 19 responsibility of reviewing adverse event 1639 20 forms for about a year and a half; right? 21 A. Thereabouts. 22 Q. And over that period of time, 23 you reviewed many, many adverse event reports 24 related to Fluoxetine and other drugs. Page 192 1 A. During that year and a half, I 2 reviewed them just for Fluoxetine. 3 Q. Okay. But there were many, 4 many that you did review over that period of 5 time? 6 A. Yes. 7 Q. Adverse events related to 8 Fluoxetine as a whole, would you say that you 9 reviewed more than a thousand over that year and 10 a half? 11 A. Probably. 12 Q. As part of your 13 responsibilities in reviewing 1639s, were you to 14 decide whether or not an adverse event was 15 considered serious under the FDA regulations? 16 A. Yes. 17 Q. Do you remember what the FDA 18 criteria was for considering an adverse event 19 serious? 20 A. I do not recall all of the 21 criteria, but some of them include 22 hospitalization, death, and some others along 23 those lines. 24 Q. Congenital anomaly? Page 193 1 A. Yes, that's one of them. 2 Q. Cancer? 3 A. I believe so. 4 Q. Overdose? 5 A. I believe so. 6 Q. Life threatening? 7 A. Yes. 8 Q. And how about prescription 9 drugs? 10 A. I do not believe that was a 11 criteria for seriousness. 12 Q. Besides death, hospitalization, 13 congenital anomaly, cancer, overdose and 14 life-threatening, can you think of any others? 15 A. I cannot think of any others at 16 this time. 17 Q. Okay. With regards to 18 life-threatening, how was life-threatening 19 defined? 20 A. Just very subjective. Each 21 physician that signed off on the reports 22 evaluated each case individually, and if they 23 felt it was serious enough to be 24 life-threatening, then they indicated that Page 194 1 category. 2 Q. Okay. So it was done within 3 the physician's own medical judgment? 4 A. That's right. 5 Q. How about expectedness or 6 expectancy of the adverse event, did you have 7 responsibility to assign expectancy? 8 A. Yes. 9 Q. How was expectancy defined? 10 A. If I recall, and the best of my 11 recollection, if the adverse event term were part 12 of the package insert, then it was expected. 13 Q. Anything else that you can look 14 at to determine expectancy besides the package 15 insert related to spontaneous adverse events? 16 A. Not that I can recall for 17 spontaneous adverse event reports. 18 Q. Would you refer to the package 19 insert for those adverse events that you reviewed 20 that you weren't sure if they were listed or not 21 or how would you determine whether or not an 22 adverse event was listed in the package insert? 23 A. Initially I would refer to the 24 package insert, but after a while I got to know Page 195 1 them fairly well so I wouldn't have to refer to 2 it as frequently. 3 Q. Where on the package insert 4 would you look? In other words was it the 5 package insert generally or was there specific 6 sections in the package insert that applied to 7 expectancy? 8 A. Typically in the adverse event 9 and post-marketing sections, although it could 10 have been anywhere throughout the package insert. 11 Q. Does there have to be some sort 12 of relationship with the drug listed in the 13 package insert, and I'm not talking about a 14 causal relationship, but some sort of 15 relationship with the drug listed with the 16 adverse event for it to become expected? 17 MR. MYERS: Let me object to the form 18 only to the extent that if it's not a causal 19 relationship, what other kind of relationship is 20 there? 21 Q. For instance in the 22 post-marketing section of the package insert, it 23 doesn't assign causality, it says this is what 24 we've seen post-marketing, there have been Page 196 1 reports of suicidality or whatever. 2 A. Could you please read the 3 question back again? 4 (THE COURT REPORTER READ BACK THE 5 REQUESTED TESTIMONY.) 6 A. Could you restate your 7 question? 8 Q. I'm trying to figure out -- I 9 mean, for instance, let's talk about suicidal 10 ideation or suicide attempt. There's no causal 11 relationship to the use of Fluoxetine and 12 suicidal ideation or suicide attempt listed in 13 the package insert to your knowledge, is there? 14 A. I lost my train of thought, I'm 15 sorry. 16 Q. That's okay. To your 17 knowledge,in the package insert for Fluoxetine, 18 as it exists say today, okay, is there a mention 19 in the package insert that suicide, suicidal 20 ideation, suicide attempt is related to using 21 Fluoxetine? 22 A. I do not recall if that's in 23 the package insert or not. 24 Q. Let's say that suicide is Page 197 1 mentioned in the package insert in the context of 2 the disease depression as being something that is 3 seen in people who are suffering from depression 4 generally, okay. Would that mention, that type 5 of mention in and of itself make suicide or 6 suicidal ideation an expected adverse event? 7 A. In that particular example, I 8 don't know, I wouldn't think so, but I don't 9 know. 10 Q. Did you have responsibility in 11 reviewing 1639s to determine a causal 12 relationship between Fluoxetine and a given 13 adverse event? 14 A. I had to assign for serious 15 events if there was a possible association 16 between the event and the drug, yes. 17 Q. What criteria would you use to 18 make that determination? 19 A. It was very case by case 20 specific, it involved medical judgment. 21 Q. Was it subjective again? 22 A. We used all available 23 information, any objective medical information 24 present in the report, and made a judgment based Page 198 1 on that. 2 Q. So it was a medical judgment, 3 again, made based on information you had from the 4 report? 5 A. Right. 6 Q. Were there adverse events that 7 had been predetermined by anybody at Lilly that 8 were not causally related to the use of 9 Fluoxetine? 10 A. Not that I'm aware of. 11 Q. Did you ever see a case of 12 suicide or suicidal ideation that you felt was 13 related to Fluoxetine? 14 A. I seem to recall when I very 15 first joined the group and started signing off on 16 adverse events as I was learning about the 17 disease, I tended to take the Lilly approach 18 which is to be very conservative. Given absence 19 of data, one could not say one way or the other, 20 and I believe I signed off on some in a 21 conservative manner and said there was a possible 22 association. So I seem to recall doing that. 23 Q. Was there a time when you 24 stopped doing that in regards to suicide or Page 199 1 suicidal ideation? 2 A. The more I learned about the 3 disease and the more I read, there was a time 4 when I stopped doing that, I think it was fairly 5 soon. 6 Q. Did anybody at Lilly tell you 7 to stop doing that? 8 A. No. 9 Q. What did you read with regards 10 to depression that made you change your mind with 11 regards to the association between suicidal 12 ideation and the use of Fluoxetine? 13 A. I read all kinds of things, I 14 mean medical textbooks, articles, listening to 15 consultants, they explained the disease, a number 16 of inputs that I received, just a number of 17 sources. 18 Q. Did you read any of the 19 literature that's out there that discusses an 20 association between Fluoxetine and suicidal 21 ideation, such as Doctor Teicher's article? 22 A. I remember reading that at that 23 time, yes. 24 Q. Did you read any other articles Page 200 1 associating Fluoxetine with suicidal ideation? 2 A. I remember seeing some case 3 reports in the literature that I recall right 4 now, there may have been others I'm not recalling 5 at this time. 6 Q. But you didn't think that those 7 case reports were correct? 8 A. Based on the body of evidence 9 as I learned more over time, I made assessments 10 given the Gestalt of the information in my 11 learning. 12 Q. What do you mean when you say 13 the Gestalt of the information? 14 A. Taking all the information 15 together and making the best decisions I could 16 and best judgments I could. 17 Q. How about Fluoxetine and 18 violent aggressive behavior, do you recall ever 19 assigning causal relationship between the use of 20 Fluoxetine and violent aggressive behavior? 21 A. I do not recall if I did, I 22 could have, but I do not recall. 23 Q. Did you have responsibility to 24 decide whether or not a follow-up should be Page 201 1 conducted on any given adverse event that was 2 reported that you reviewed? 3 A. Yes. 4 Q. And in what situations would 5 you require a follow-up? 6 A. Typically where there was an 7 absence of pertinent information about the 8 patient. 9 Q. Such as? 10 A. It would depend on the 11 particular adverse event report. For example, if 12 it were a report of hemorrhage, there would be a 13 number of questions I would want to know, please 14 give me details of the specific bleeding event, 15 please give me any laboratory parameters of the 16 patient, what concomitant medications were they 17 on, did they have any underlying illnesses or 18 preexisting bleeding disorders. It would all 19 depend on the specific adverse event, and if 20 those weren't present in a report, then those 21 were things I would deem necessary to have. 22 Q. How about with regards to 23 violent aggressive behavior, what kind of 24 questions would you want answered in follow-up? Page 202 1 A. Again, short of having any 2 specific report to comment on, I can only speak 3 hypothetically. 4 Q. That's fine. 5 A. I would certainly want to know 6 if the patient had any other underlying 7 psychiatric and/or medical illnesses, what types 8 of other medications they may have been on, 9 previous episodes, among others. I'm sure there 10 are probably others I would think of. 11 Q. In and of itself, would a 12 previous episode of violent aggressive behavior 13 while not on Fluoxetine eliminate a causal 14 relationship between Fluoxetine and violent 15 aggressive behavior? 16 A. I do not know, I suppose that 17 would depend on each individual review. 18 Q. How about suicidal ideation, 19 would a previous history of suicidal ideation 20 prior to using Fluoxetine rule out a causal 21 connection between the use of Fluoxetine and 22 increase of suicidal ideation in and of itself? 23 A. Could I have you repeat your 24 question and maybe break it down, please? Page 203 1 MS. ZETTLER: Can you read it back? 2 (THE COURT REPORTER READ BACK THE 3 REQUESTED TESTIMONY.) 4 A. Again, each case I would 5 evaluate independently, and if I had information 6 about prior suicidal ideation, it would be one 7 piece of the information I would use to make my 8 judgment, but it may not necessarily influence 9 the way I judged a particular event. 10 Q. But there was a point in time 11 when you stopped assigning causal relationship 12 between suicidal ideation and the use of 13 Fluoxetine altogether; correct? 14 A. I don't recall if I varied the 15 way I signed them initially, depending on what I 16 learned, depending on the amount of information I 17 had. But after a while, I continued to judge 18 each one individually. But if you ask me if I 19 recall signing possible associations later, I 20 don't recall doing that. That doesn't mean I 21 didn't, but I don't recall doing it. 22 Q. Did you have responsibility to 23 determine whether or not a particular act by a 24 patient was actually a suicide gesture? Page 204 1 A. Sure, I would have the 2 responsibility of filling in all of the adverse 3 events in a report based on my interpretation of 4 the report, including possible suicidal acts. 5 Q. When you say filling in the 6 adverse event, you mean assigning terms to the 7 narratives? 8 A. Exactly. 9 Q. Was there ever a time that you 10 can recall where a reporter reported that 11 somebody had made a suicide attempt while using 12 Fluoxetine and you disagreed with that assessment 13 and did not term it a suicide attempt? 14 A. I don't recall if I did that. 15 Q. You could have, but you just 16 don't remember? 17 A. I tended to rarely disagree 18 with what was reported by -- in fact I don't 19 recall disagreeing with what was reported. 20 Q. By the initial reporter? 21 A. Right. 22 Q. How about overdose, was 23 overdose always considered a serious adverse 24 event? Page 205 1 MR. MYERS: Well, I object to the form 2 only to the extent that he testified about five 3 minutes ago that it was by definition serious 4 from the regulatory definition. So he's already 5 answered that. 6 A. Right, that's what I was going 7 to say, per the regulatory definition, I would. 8 I mean as I recall, those would be considered 9 serious. 10 Q. What if somebody intentionally 11 took five hundred milligrams of Fluoxetine but 12 had no ill effects from it? 13 A. I believe we -- or I seem to 14 recall designating those as overdose if they were 15 over the prescribing limits. 16 Q. Okay. But if no harm came to 17 the person as a result of ingesting the five 18 hundred milligrams of Fluoxetine, would that be 19 reported as an adverse event? 20 A. I believe it would have been, I 21 think so. 22 Q. What did you do to make sure 23 that follow-up was done on those reports where 24 you wanted follow-up done? Page 206 1 A. Well, there were several ways 2 follow-ups were conducted. One of them is I 3 would personally follow-up, another way is the 4 very good capable DEU CRAs at Lilly would do the 5 follow-up, and they would do that either by 6 direct telephone call and/or a letter to the 7 reporter for more information, based on a request 8 that I would put for more follow-up information. 9 Q. When you did the movement 10 disorder event collection and review, were those 11 spontaneous adverse events or were those clinical 12 trial adverse events or both? 13 A. Is this the movement disorder 14 review that was done with the outside 15 consultants? 16 Q. Right. 17 A. I believe -- I don't recall 18 exactly, but I believe they were any adverse 19 event reports in our DEN data base, which would 20 have included both spontaneous post-marketing 21 reports as well as clinical trial reports, but I 22 don't recall. Specifically I would need to 23 review the materials which we sent before I could 24 tell you. Page 207 1 Q. When you say the DEN data base 2 included all clinical trial adverse events, do 3 you mean all adverse events that occurred in 4 clinical trials or only those that were 5 determined to be serious? 6 MR. MYERS: I object to the form, I 7 don't think he said all clinical trials events, 8 he said clinical trial events. 9 Q. That's what I'm trying to find 10 out. 11 A. Events in the DEN data base. 12 Q. Okay. 13 A. You would have to talk to 14 somebody who is more knowledgable about the DEN 15 data base, but I believe it certainly included 16 the spontaneous reports. It may have also 17 included the clinical trial reports in the DEN 18 data base, which I cannot recall if those were 19 all clinical trial reports or just those that 20 were serious or what the criteria was. I would 21 need to review, again, those materials to answer 22 you better. 23 Q. Wouldn't you have liked to 24 review all the clinical trial adverse events Page 208 1 regarding movement disorders as well as the 2 spontaneous adverse events? 3 A. I believe internally we 4 undertook that project, and that was one of the 5 exhibits to which you referred. 6 Q. To your knowledge was any other 7 source other than the DEN data base searched for 8 evidence of movement disorder events? 9 A. Regarding our overall review of 10 movement events, exclusive of -- 11 Q. Right. 12 A. I mean not just including the 13 outside consultants, but any review we undertook? 14 Q. Sure. 15 A. Yes, I believe we reviewed our 16 clinical trial data base. 17 Q. Okay. Now how is your overall 18 review different than -- different from the 19 review done by the outside consultants? 20 A. Internally there was no 21 difference in the way we evaluated each of the 22 movement event reports, whether we got them from 23 the clinical trial data base or whether we got 24 them from the DEN data base. However, the only Page 209 1 difference is the outside consultants got all the 2 materials from our DEN data base because that's 3 what we had available to give to them at the 4 time. 5 Q. Now you're confusing me. Are 6 you saying that there were more movement disorder 7 related adverse events contained or found as a 8 result of the internal review than were given to 9 the consultants to look at? 10 A. Again, I would need to review 11 how the DEN data base is set up. I think it's 12 set up such that it contains clinical trial 13 reports that are serious. I don't think the DEN 14 data base has clinical trial reports that are 15 nonserious, and for those you would have to go 16 back to the clinical trial data base. Thus our 17 internal review was as comprehensive as it could 18 be. 19 Q. But the adverse events reports 20 that you turned over to the outside consultants 21 were only those reports that were found in the 22 DEN data base? 23 A. I believe that's correct, but I 24 believe it's correct because -- I believe it's Page 210 1 correct. 2 Q. Okay. 3 (PLAINTIFFS' EXHIBIT NO. 22 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to review 7 Exhibit 22? 8 A. Yes. 9 Q. Do you recognize this exhibit? 10 A. Yes. 11 Q. Tell me what it is? 12 A. I believe it's a list of 13 adverse event terms that was in the Prozac 14 package insert at that time. 15 Q. Do you know what time frame 16 we're talking about here? 17 A. No, I do not. 18 Q. On page Pz 2445 841, it looks 19 like under Donna Pearson's name, it says Donna P, 20 looks like 10-15-90? 21 A. It sort of looks like that. 22 Q. When you were assigning 23 expectancy to adverse events when you were 24 reviewing 1639s, did you refer to this list or Page 211 1 any list like it to determine whether or not an 2 adverse event was expected? 3 A. I did use this list after a 4 while. 5 Q. Okay. 6 A. Yes. 7 Q. Was such a list available prior 8 to this list? 9 A. I do not recall if there was a 10 list available prior to this list. 11 Q. And the next page, 842, in the 12 bottom corner it has an asterisk and it says 13 non-ELECT term, and then it has a double asterisk 14 and it says new ELECT term. Do you see that? 15 A. Yes. 16 Q. Under accidental overdose -- 17 next to accidental overdose it has two asterisks. 18 Do you recall when accidental overdose was added 19 as an ELECT term? 20 A. I do not recall. 21 Q. What is flu syndrome, on the 22 next page? 23 A. I believe it captures reports 24 of flu. Page 212 1 Q. Have you heard reports of 2 people using Fluoxetine suffering from a flu like 3 syndrome and dying, becoming very ill? 4 A. I do not recall reports like 5 that. 6 Q. Have you ever heard of the term 7 seratonin syndrome? 8 A. Yes, I have heard the term. 9 Q. Can you tell me what seratonin 10 syndrome is? 11 A. I do not know exactly what 12 seratonin syndrome is. 13 Q. Where did you hear the term? 14 A. In my review of neuroleptic 15 malignant syndrome reports, I heard about, read 16 about, seratonin syndrome, that's where I heard 17 about it. 18 Q. What's the difference between 19 neuroleptic malignant syndrome and, say, tardive 20 dyskinesia? 21 A. I do not recall what 22 neuroleptic malignant syndrome is, so I cannot 23 differentiate the two for you. 24 Q. But you have done research on Page 213 1 the syndrome? 2 A. I remember reading about it and 3 being aware of it several years ago, but I have 4 forgotten since. 5 Q. How about akathisia, what's the 6 difference between tardive dyskinesia and 7 akathisia? 8 A. Tardive dyskinesia is chronic 9 involuntary movement disorders following 10 prolonged course of neuroleptic therapy, and 11 akathisia is perceived restlessness, not 12 necessarily involuntary movements, it's different 13 than that. 14 Q. When you say not necessarily, 15 can it include akathisia involuntary movement? 16 A. I'm unaware of that, no. 17 Q. When you say involuntary 18 movements, what kind of movements are you talking 19 about? 20 A. Any type of involuntary 21 muscular movement. 22 Q. Would that include pacing? 23 A. I don't think it does. 24 Q. Would that include, like, Page 214 1 tapping of feet or moving of hands? 2 A. If the movements are 3 involuntary, then yes, tardive dyskinesia could 4 include that. 5 (PLAINTIFFS' EXHIBIT NO. 23 WAS 6 MARKED FOR IDENTIFICATION AND 7 RECEIVED IN EVIDENCE.) 8 Q. Have you had a chance to review 9 Exhibit 23? 10 A. I have read it, and it also 11 points out in writing that the information 12 provided to our consultants who reviewed movement 13 disorder reports were spontaneous reports. But 14 again, like we said earlier, it would be helpful 15 to review the material sent just to confirm that. 16 Q. But this indicates that there 17 were spontaneous reports? 18 A. This is what this memo says. 19 Q. Okay. The second sentence of 20 the memo says in spite of diligent follow-up on 21 many of the reports, most likely that would 22 include information to make any ruling about the 23 actual event; correct? 24 A. It does say that, correct. Page 215 1 Q. Then you say following the 2 first rule of EPI -- I assume you mean 3 epidemiology? 4 A. Yes. 5 Q. -- we were in the process of 6 recontacting the reporters. What do you mean by 7 the first rule of EPI? 8 A. Confirm the diagnosis. 9 Q. Did you feel that in many of 10 those reports the diagnosis was not confirmed? 11 A. There was no description of the 12 event and an inadequate description of the 13 patient to support a report of tardive 14 dyskinesia. 15 Q. On how many of those reports 16 were you successful in getting sufficient 17 information? 18 A. I do not recall that number. 19 Q. Can you give me an idea, was it 20 most of the reports? 21 A. I know we were able to obtain 22 follow-up information on some of the patients, 23 but I do not remember the number. 24 Q. More than one? Page 216 1 A. More than one. 2 MR. MYERS: Numerous. 3 Q. Numerous. Who developed the 4 list of questions to ask the reporters for 5 information about the patients and events? 6 A. I was involved in that, and I 7 got help from Charles Beasley. 8 Q. Who helped you with the 9 follow-up information? 10 A. I did some of it, and some of 11 the DEU CRAs did some of it. 12 Q. What kind of questions were on 13 the list? 14 A. As I recall, we asked questions 15 about other drug exposures, particularly 16 neuroleptic agents. We asked questions about 17 other psychotropic illnesses, such as Parkinson's 18 disease, we asked questions about trauma, such as 19 head trauma, particularly head trauma, we asked 20 questions about the specific movement event, 21 please describe it, or what's its temporal 22 nature, what muscle groups are involved. 23 Questions along those lines. 24 Q. The second paragraph here, it Page 217 1 says once letters of confidentiality have been 2 received, we will send out the approximately five 3 hundred reports to each of three consultants. I 4 believe that's Doctor Klawans and Doctor Glaser? 5 A. Correct. 6 Q. And who else? 7 A. We did not have a third 8 consultant. 9 Q. And then you say confirming 10 that no reports of TD were collected in the 11 controlled double-blind Fluoxetine clinical 12 trial; correct? 13 A. The memo states that, correct. 14 Q. What did you do to confirm and 15 reconfirm that there were no reports of tardive 16 dyskinesia in the collecting of the clinical 17 trial? 18 A. Per one of the previous 19 exhibits, we had that we reviewed the proposal 20 that outlined the approach to review the clinical 21 trial data. 22 Q. Okay. To your knowledge was 23 tardive dyskinesia or tardive dystonia an ELECT 24 term as applied to the clinical trial data base Page 218 1 prior to January of 1990? 2 A. I don't believe so. 3 Q. What did -- what would tardive 4 dyskinesia have mapped to if it had been reported 5 in the clinical trial? 6 A. I don't know for certain, but 7 probably extrapyridimal syndrome and maybe some 8 others. 9 Q. Were all of the extrapyridimal 10 syndrome adverse events reviewed to determine 11 whether or not they were in fact tardive 12 dyskinesia or tardive dystonia? 13 A. We would have to review the 14 proposal to see -- one of the prior exhibits to 15 see what was outlined. 16 Q. Do you have a recollection as 17 to whether or not that was done? 18 A. I need to review the exhibit. 19 Q. Sure. 20 A. It's Exhibit 21. Could you 21 please reread the question? 22 (THE COURT REPORTER READ BACK THE 23 REQUESTED TESTIMONY.) 24 A. If a review was undertaken, I Page 219 1 believe it would have been done electronically, 2 in other words identify extrapyridimal syndrome 3 reports and see if there are any character 4 strings to indicate dyskinesia or dystonia. I 5 believe that's the way it would have been done 6 based on what I read here. 7 Q. So is it possible that somebody 8 could have described an incident of tardive 9 dyskinesia without using that specific term and 10 it would not have been picked up in the 11 electronic search? 12 A. Unlikely. 13 Q. Why? 14 A. Not impossible, but unlikely. 15 Q. Why? 16 A. Because most of the 17 investigators would probably refer to the event 18 as they saw it. For example, if it were a 19 dyskinetic movement, it probably would have said 20 dyskinesia, or dystonic movement they probably 21 would have said dystonia. But given there were 22 no ELECT terms for that, those descriptions were 23 mapped to terms such as extrapyridimal syndrome. 24 So if there was an electronic search for those Page 220 1 character strings it would help uncover those 2 types of reports. 3 Q. Do you know why tardive 4 dyskinesia and tardive dystonia were not included 5 as ELECT terms before 1990? 6 A. I don't know why. 7 Q. Would you as a clinical 8 research physician have authority to have those 9 terms added to the ELECT dictionary? 10 A. I do not know. 11 Q. Did you ever seek to have any 12 event terms listed in the ELECT -- or included in 13 the ELECT dictionary? 14 A. I have not. My understanding 15 is that our ELECT dictionary, I believe, almost 16 identically replicated the COSTART FDA 17 dictionary. 18 Q. Why not use the COSTART then? 19 A. I don't have an answer, I don't 20 know. 21 Q. What diferences were there 22 between the COSTART and the ELECT? 23 A. Extremely small differences, 24 but I don't recall what they are. Page 221 1 Q. Who would know why they would 2 use the ELECT dictionary as opposed to the 3 COSTART if they were so similar? 4 A. Probably Max Talbott would 5 know. 6 Q. Have you ever heard that an 7 adverse event is considered unexpected even if 8 it's listed in the package insert if the event 9 differs from the label in nature, severity or 10 specificity? 11 A. Would you repeat that, please? 12 Q. Sure. With regards to 13 expectancy, which we have established is 14 determined by whether or not an event is listed 15 in the package insert; correct? 16 A. Correct. 17 Q. Okay. Have you ever heard with 18 regards to expectancy a policy that an event is 19 to be considered unexpected if it differs from 20 the package insert in nature, severity or 21 specificity, in other words it's listed in the 22 package insert, but the particular adverse event 23 that you are looking at differs from the way it's 24 listed in the package insert? Page 222 1 MR. MYERS: To the extent your question 2 assumes that is true, I object to the form. He 3 can tell you whether he knows if that's the case 4 or not. 5 MS. ZETTLER: All I asked him is if he 6 had ever heard of that policy. 7 MR. MYERS: I object to the form. Tell 8 her if you know. 9 A. I'm unaware of any policy, I 10 don't know about one. 11 Q. Have you ever heard of a policy 12 at Lilly that overdose was not reportable unless 13 it was associated with a symptom other than 14 simply the overdose? 15 MR. MYERS: Same objection. 16 A. I don't recall of any policy, 17 and I don't know of any policy. 18 Q. Is it your understanding that 19 overdose as of late '88 or early 1989 included 20 the synonymous terms of intentional overdose and 21 accidental overdose? 22 MR. MYERS: When you say term, do you 23 mean the dictionary term? 24 MS. ZETTLER: The event term. Page 223 1 A. Please repeat the question. 2 Q. Sure. Was it your 3 understanding that as of late '88 or early '89, 4 it was decided that any incidents of accidental 5 overdose would be assigned the event term of 6 overdose, as well as any incidents of intentional 7 overdose? 8 A. I don't recall. 9 Q. How about assigning the event 10 term depression to an act indicating suicidal 11 ideation? 12 MR. MYERS: Same point in time? 13 Q. Any point in time. 14 A. Repeat your last part of the 15 question again, please. 16 Q. Sure. Is it your understanding 17 that the event term depression was to be assigned 18 to an adverse event that indicated either 19 increased or emergent suicidal ideation? 20 A. I do not recall how suicidal 21 ideation mapped during that time period. It 22 seems to me it may have mapped to depression, but 23 I don't recall, I don't remember how it mapped. 24 Q. Okay. Do you recall assigning Page 224 1 the event term of suicide attempt to completed 2 suicide? 3 A. I don't recall that. 4 MS. ZETTLER: Okay. That's all I have. 5 MR. MYERS: No questions. 6 (THE WITNESS WAS EXCUSED.) Page 225 1 COMMONWEALTH OF KENTUCKY ) 2 : ss COUNTY OF JEFFERSON ) 3 4 I, MARY KATHLEEN NOLD, A NOTARY PUBLIC IN 5 AND FOR THE STATE OF KENTUCKY AT LARGE, DO HEREBY 6 CERTIFY THAT THE FOREGOING TESTIMONY OF 7 JAMES KOTSANOS, M.D. 8 WAS TAKEN BEFORE ME AT THE TIME AND PLACE AS 9 STATED IN THE CAPTION; THAT THE WITNESS WAS FIRST 10 DULY SWORN TO TELL THE TRUTH, THE WHOLE TRUTH, 11 AND NOTHING BUT THE TRUTH; THAT THE SAID 12 PROCEEDINGS WERE TAKEN DOWN BY ME IN STENOGRAPHIC 13 NOTES AND AFTERWARDS TRANSCRIBED UNDER MY 14 DIRECTION; THAT IT IS A TRUE, COMPLETE AND 15 CORRECT TRANSCRIPT OF THE SAID PROCEEDINGS SO 16 HAD; THAT THE APPEARANCES WERE AS STATED IN THE 17 CAPTION. 18 WITNESS MY SIGNATURE THIS THE 11TH DAY OF 19 NOVEMBER, 1993. 20 MY COMMISSION EXPIRES MARCH 10, 1994. 21 22 23 _________________________ MARY KATHLEEN NOLD 24 COURT REPORTER AND NOTARY PUBLIC STATE OF KENTUCKY AT LARGE Page 226 1 2 3 E R R A T A S H E E T 4 5 COMMONWEALTH OF KENTUCKY ) : SS 6 COUNTY OF JEFFERSON ) 7 8 I, JAMES KOTSANOS, M.D., THE 9 UNDERSIGNED DEPONENT, HAVE THIS DATE READ THE 10 FOREGOING PAGES OF MY DEPOSITION AND WITH THE 11 CHANGES NOTED BELOW, IF ANY, THESE PAGES 12 CONSTITUTE A TRUE AND ACCURATE TRANSCRIPTION OF 13 MY DEPOSITION GIVEN ON THE 21ST DAY OF OCTOBER, 14 1993 AT THE TIME AND PLACE STATED THEREIN. 15 PAGE NO. LINE NO. CHANGE REASON Page 227 1 2 PAGE NO. LINE NO. CHANGE REASON 3 4 5 6 7 8 9 _____________________________ 10 JAMES KOTSANOS, M.D. 11 SWORN TO AND SUBSCRIBED BEFORE ME THIS 12 _____ DAY OF __________, 1993. 13 _____________________________ NOTARY PUBLIC, STATE OF 14 KENTUCKY AT LARGE Page 228 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Page 229 1 COMMONWEALTH.....................................226 2 PLAINTIFFS' EXHIBIT NO. 4.........................37 3 PLAINTIFFS' EXHIBIT NO. 5.........................50 4 PLAINTIFFS' EXHIBIT NO. 6.........................54 5 PLAINTIFFS' EXHIBIT NO. 7.........................60 6 PLAINTIFFS' EXHIBIT NO. 8.........................67 7 PLAINTIFFS' EXHIBIT NO. 9.........................95 8 PLAINTIFFS' EXHIBIT NO. 10........................99 9 PLAINTIFFS' EXHIBIT NO. 11.......................114 10 PLAINTIFFS' EXHIBIT NO. 12.......................117 11 PLAINTIFFS' EXHIBIT NO. 13.......................126 12 PLAINTIFFS' EXHIBIT NO. 14.......................142 13 PLAINTIFFS' EXHIBIT NO. 15.......................144 14 PLAINTIFFS' EXHIBIT NO. 16.......................154 15 PLAINTIFFS' EXHIBIT NO. 17.......................161 16 PLAINTIFFS' EXHIBIT NO. 18.......................164 17 PLAINTIFFS' EXHIBIT NO. 19.......................166 18 PLAINTIFFS' EXHIBIT NO. 20.......................176 19 PLAINTIFFS' EXHIBIT NO. 21.......................183 20 PLAINTIFFS' EXHIBIT NO. 22.......................211 21 PLAINTIFFS' EXHIBIT NO. 23.......................215 22 E R..............................................227 Page 230