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: MICHAEL S. NOONE 11 DATE: OCTOBER 19TH AND 20TH, 1993 12 13 * * * * * * * * * * 14 15 16 REPORTER: KATHY NOLD 17 18 KENTUCKIANA REPORTERS SUITE 260 19 730 WEST MAIN STREET LOUISVILLE, KENTUCKY 40202 Page 1 1 * * * * * * * * * * 2 3 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA 4 INDIANAPOLIS DIVISION 5 IN RE ELI LILLY AND COMPANY ) Prozac Products Liability ) MDL Docket No. 907 6 Litigation ) 7 * * * * * * * * * * 8 NO. 91-02496-A 9 JACKIE LYNN BIFFLE, ET AL ) IN THE DISTRICT ) COURT OF 10 V. ) DALLAS COUNTY, TEXAS ) 11 ELI LILLY & COMPANY AND ) 14TH JUDICIAL DISTA PRODUCTS COMPANY ) DISTRICT 12 * * * * * * * * * * 13 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 MICHAEL S. NOONE, TAKEN AT 2 THE OFFICE OF BAKER & DANIELS, 300 NORTH MERIDIAN 3 STREET, SUITE 2700, INDIANAPOLIS, INDIANA 46204, 4 ON OCTOBER 19TH AND 20TH, 1993; SAID DEPOSITION 5 TAKEN PURSUANT TO NOTICE IN ACCORDANCE WITH THE 6 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 MICHAEL S. NOONE 4 5 DIRECT EXAMINATION BY MR. SMITH 7 6 CROSS EXAMINATION BY MS. ZETTLER 260 7 CERTIFICATE 491 8 ERRATA 492 9 10 CERTIFIED QUESTION 62 11 CERTIFIED QUESTION 67 12 13 EXHIBITS 14 PLAINTIFFS' EXHIBIT NO. 1 137 15 PLAINTIFFS' EXHIBIT NO. 2 291 16 PLAINTIFFS' EXHIBITS 3, 4 AND 5 330 17 PLAINTIFFS' EXHIBIT NO. 6 375 18 PLAINTIFFS' EXHIBIT NO. 7 403 19 PLAINTIFFS' EXHIBIT NO. 8 415 20 PLAINTIFFS' EXHIBIT NO. 9 449 21 PLAINTIFFS' EXHIBIT NO. 10 452 22 PLAINTIFFS' EXHIBIT NO. 11 455 23 PLAINTIFFS' EXHIBIT NO. 12 474 24 PLAINTIFFS' EXHIBIT NO. 13 479 Page 6 1 COMES MICHAEL S. NOONE, CALLED BY THE 2 PLAINTIFFS, AND AFTER FIRST BEING DULY SWORN, WAS 3 DEPOSED AND TESTIFIED AS FOLLOWS: 4 DIRECT EXAMINATION 5 BY MR. SMITH: 6 Q. Would you state your full name, 7 please, sir. 8 A. Michael S. Noone. 9 MR. MYERS: Before you start, just so 10 the record is clear, Mister Noone is here by 11 agreement in the Fentress case, there's not a 12 notice and we're producing him in the Fentress 13 case. There's also, as I understand it, a cross 14 notice out in the MDL proceedings and in the 15 Saines case in California, and that accounts for 16 the presence or absence of some of the lawyers 17 that have been with us in the past. 18 MR. RUIZ: And I would like to state 19 for the record that I'm present on behalf of Dr. 20 Denson involved in the Maloney versus Eli Lilly 21 case, and he is a respondent in discovery, not a 22 defendant. As such he has filed a special 23 limited appearance, and by appearing here today 24 we do not waive any challenge to the court's Page 7 1 jurisdiction. 2 MR. MYERS: Thank you. 3 Q. Mister Noone, you and I met 4 previously; correct? 5 A. Yes. 6 Q. It is Noone, not Noony; 7 correct? 8 A. That is correct. 9 Q. You have appeared in a Texas 10 state court case and given your deposition in the 11 Texas state court case, and additionally that 12 deposition has been used in the multi-district 13 litigation also. Do you understand that in 14 giving your deposition in those proceedings? 15 A. Yes, if you say that's for what 16 it was used, yes. 17 Q. Have you had an opportunity to 18 read your previous testimony that you've given in 19 the Biffle case? 20 A. I did on one occasion, yes, 21 sir. 22 Q. Have you read that deposition 23 completely through? 24 A. Define completely. Page 8 1 Q. Read every page. 2 A. As I recall, I did, yes. 3 Q. Did you make any corrections, 4 additions or deletions from that deposition? 5 A. I don't remember. 6 Q. Had you made any corrections or 7 additions or deletions to that deposition, what 8 would you have done with it, returned it to Ms. 9 Huff possibly or somebody at legal? 10 A. Yes. 11 Q. Do you remember when that might 12 have been that you reviewed your deposition? 13 A. No, I don't. 14 Q. Have you given any testimony in 15 any Prozac cases other than that deposition that 16 we mentioned -- that we just mentioned? 17 A. It seems to me that's the only 18 one. 19 Q. Have you given your deposition 20 in any case, in any litigation, since your 21 deposition was taken in the Biffle matter, and I 22 believe that was June, 1992 when you gave your 23 deposition? 24 A. No. Page 9 1 Q. Have you done any work in 2 connection with the Prozac litigation since you 3 gave your deposition in June, 1992? 4 A. Define any work. 5 Q. Any work that you've been asked 6 to do in connection with any litigation by the 7 legal department, and to give you some assistance 8 in that -- I know you've written affidavits on a 9 couple of occasions in the Biffle Texas state 10 court litigation, and I'm wondering if you've 11 given any affidavits or consulted in any other 12 cases? 13 A. I don't recall having completed 14 any other affidavits subsequent to that June, 15 '92. 16 Q. Do you remember any other 17 substantive work you might have done in 18 connection with Prozac litigation with anybody 19 from the legal department? 20 A. Do I remember any? 21 Q. Yes. 22 A. I remember some discussions 23 that I've had, yes. 24 Q. When would those discussions Page 10 1 have occurred? 2 A. I really couldn't tell you the 3 specific time, it's been quite a while since I 4 have been involved with any of that. 5 Q. Would that have been in 6 scheduling court appearances or deposition or 7 would that have been in securing additional 8 documents or doing additional work? 9 A. Periodically I receive notices 10 that go out to send any documents that I might 11 have relative to Prozac. 12 Q. I believe, in deposing other 13 individuals at Lilly, it's been determined that 14 most departments are submitting their documents 15 quarterly. Would that be accurate with respect 16 to what you've done? 17 A. Yes. 18 Q. Do you still maintain a Prozac 19 file? 20 A. There was a file that I had, I 21 don't remember now if it was even labeled Prozac, 22 that I sent those documents over to legal. My 23 current job does not really involve much with 24 that. Page 11 1 Q. When would have been the last 2 time that you submitted any Prozac information to 3 legal? 4 A. If I had to guess, somewhere in 5 the neighborhood of two to three or four months 6 ago. 7 Q. What was that, do you remember? 8 A. I don't remember. 9 Q. Was that documents that you had 10 received that had come in over a period of time 11 that needed to be forwarded? 12 A. The only thing I can remember 13 is that I had a file that had some information 14 that at least mentioned the word, and, so, that 15 was what was sent over. 16 Q. Do you remember what that was? 17 A. No, I didn't look at it in any 18 detail. 19 Q. What is your current job with 20 Lilly? 21 A. It's called manager of clinical 22 research coordination. 23 Q. How long have you had that? 24 A. Since approximately December of Page 12 1 '92. 2 Q. And the job you had before that 3 was? 4 A. Manager medical regulatory 5 affairs. 6 Q. I believe your testimony was in 7 your previous deposition that you began as 8 manager of medical regulatory affairs in, like, 9 1988? 10 A. That's true. 11 Q. So from 1988 until December of 12 1992 you were the manager of medical regulatory 13 affairs? 14 A. Right. 15 Q. And before that, you were a 16 department head in medical regulatory services. 17 Give me the exact title, if you can remember. 18 A. I think it was called something 19 about a department head in medical information 20 services, something like that. 21 Q. Why were you changed from the 22 manager of medical regulatory affairs to the 23 manager of clinical research coordination? 24 A. Just normal career progression, Page 13 1 different opportunity to have a different role in 2 the medical division. 3 Q. Did you make application for 4 that position? 5 A. We really don't have a formal 6 application process, I was just asked if I would 7 like to do that. 8 Q. Before you were asked if you 9 would like to do that, had you expressed a desire 10 to do some other job function within the Lilly 11 organization? 12 A. Periodically I would have 13 discussions with people about career opportunity, 14 but they really were of a general nature and 15 didn't get down to anything specific about I want 16 that job or I want this job. 17 Q. Who selected you as manager of 18 clinical research coordination? 19 A. I'm not sure I know who the 20 specific person was, I was asked by my current 21 executive director if I would like to do that. 22 Q. Who was that? 23 A. His name is Greg Brickler. 24 Q. What is Mister Brickler's Page 14 1 title? 2 A. Executive director. 3 Q. Executive director of what? 4 A. I'm not sure I know the words 5 after that, but he's an executive director in the 6 medical division. 7 Q. Is he the executive director in 8 the medical division or are there other executive 9 directors in the medical division? 10 A. There would be other medical 11 directors, other -- I'm sorry, you said executive 12 directors? 13 Q. You told me that Mister 14 Brickler's title was executive director in the 15 medical division. 16 A. Right. 17 Q. And I would assume you're 18 talking about the medical division of Lilly 19 research labs? 20 A. Right. 21 Q. Is that right? 22 A. Right. 23 Q. So are there other executive 24 directors in the medical division? Page 15 1 A. Yes. 2 Q. Other than Mister Brickler? 3 A. Yes. 4 Q. How are they -- how is their 5 job function divided up? 6 A. I'm trying to remember how many 7 more there are. There's one I know who is more 8 on the physician side of things who is an 9 executive director. 10 Q. Who would that be? 11 A. Doctor Tollefson. 12 Q. He's sort of in charge of the 13 physicians; is that right? 14 A. Some physicians, yes. 15 Q. Which physicians? 16 A. I couldn't tell you all their 17 names, I think he has an area called 18 psychopharmacology or central nervous system or 19 something. 20 Q. And, so, what does -- is Mister 21 Brickler a Mister or a doctor? 22 A. A Mister. 23 Q. Mister Brickler. What is his 24 capacity? If Doctor Tollefson is over the neuro Page 16 1 psychcopharmacology, what function does Mister 2 Brickler provide? 3 A. He's got responsibility for my 4 area also. 5 Q. Which is clinical research 6 coordination? 7 A. Right. And he has 8 responsibility for the clinical research -- or 9 the contract research organization where we -- 10 Q. What do you mean by that? 11 A. Well, we contract out work to 12 outside organizations on occasion. 13 Q. Outside investigators? 14 A. Yes, we work with an outside 15 contracting research organization who would 16 identify investigators. 17 Q. All right. Do you do that? 18 A. No, I don't work through the 19 contract research organizations. 20 Q. What other functions would 21 Mister Brickler provide? 22 A. He also has responsibility for 23 the administrative side of medical, medical 24 administrative side. Page 17 1 Q. Such as? 2 A. Data information that comes in 3 from clinical studies comes in to those areas. 4 Q. And would the clinical research 5 assistants and those individuals be under Mister 6 Brickler? 7 A. I don't know the term clinical 8 research assistant, that's -- 9 Q. Or administrators -- 10 A. Yes. 11 Q. -- I think is the proper term. 12 A. Yes, they would be in that 13 area. 14 Q. What other areas are under 15 Mister Brickler? 16 A. As I recall, I think that's it 17 at this point. 18 Q. All right. Let's talk about 19 your job functions currently as a manager of 20 clinical research coordination. I assume that 21 Mister Brickler is your immediate supervisor; is 22 that right? 23 A. That's correct. 24 Q. Now Doctor Talbott was your Page 18 1 supervisor when you were the manager of medical 2 regulatory affairs? 3 A. That's correct. 4 Q. And he was your immediate 5 supervisor? 6 A. Correct. 7 Q. Is Doctor Talbott still in 8 medical regulatory affairs? 9 A. Yes. 10 Q. What is his current position? 11 A. Same as it was before. 12 Q. What was his title, director -- 13 A. Director. 14 Q. Director of medical regulatory 15 affairs? 16 A. Uh-huh. 17 Q. Did Doctor Talbott have to 18 recommend you to Mister Brickler to make this job 19 change? 20 A. I don't know that -- I don't 21 know that he did or did not, I'm sure they had 22 discussions. 23 Q. Do you know if there were other 24 candidates for the position of manager of Page 19 1 clinical research coordination? 2 A. I don't know. 3 Q. Were you told that you were 4 being considered for this position prior to your 5 actually getting the position? 6 A. I was asked if I would like to 7 do that. 8 Q. And you were asked by Mister 9 Brickler? 10 A. Mister Brickler, uh-huh. 11 Q. What was your response, that 12 you would? 13 A. Yes. 14 Q. Why would you -- why did you 15 have an interest in doing that? 16 A. Well, it was an expansion of -- 17 or an increased opportunity for growth. 18 Q. Why? 19 A. Opportunity to understand more 20 about the overall division, other areas of the 21 division. 22 Q. All right. 23 A. Which helps with promotion and 24 things like that. Page 20 1 Q. Did you get a salary increase 2 as a result of changing positions? 3 A. No. 4 Q. Would this have been a lateral 5 move or an upward move? 6 A. Lateral. 7 Q. That's not uncommon? 8 A. Correct, no, that's correct. 9 Q. You may have several lateral 10 moves before you move north, I guess? 11 A. Typically, yes. 12 Q. Specifically what do you do as 13 manager of clinical research coordination? 14 A. The area that I have 15 responsibility, it's an administrative role, and 16 I have several people that work for me. Their 17 job is to primarily identify investigators for 18 new studies, and then to follow through after 19 those investigators have been selected with those 20 studies. 21 Q. Once the investigator has been 22 selected, do you have any further involvement 23 with the investigator or the study? 24 A. Me personally? Page 21 1 Q. Or your division. 2 A. Yes, they would have. 3 Q. All right. What type of 4 involvement would there be? 5 A. They would visit the sites to 6 assure that things were running smoothly. 7 Q. Was there a manager of clinical 8 research coordination prior to your getting that 9 job? 10 A. Yes. 11 Q. Who held that position? 12 A. There were two, Gary Lightfoot. 13 Q. All right. 14 A. And Tom Reis. 15 Q. Why were there two and now 16 there are one? 17 A. I'm good. There was some 18 change in focus, and so Mister Lightfoot took on 19 some different kinds of responsibilities within 20 the division. 21 Q. What did Mister Lightfoot move 22 from to? 23 A. Manager of clinical research 24 coordination to manager of contract research Page 22 1 organizations. 2 Q. What did Mister Reis's 3 functions move from to? 4 A. He moved from manager of 5 clinical research coordination to a role as a 6 field sales district manager. 7 Q. Field sales district manager? 8 A. Uh-huh. 9 Q. Was that sort of a new activity 10 for him? 11 A. I believe he had had a role 12 like that previously. 13 Q. But it had been in the past? 14 A. Right. 15 Q. It was different from what he 16 had been doing immediately before that? 17 A. That's correct. 18 Q. As manager of clinical research 19 coordination? 20 A. Correct. 21 Q. How long had Mister Lightfoot 22 been the manager, been a manager in clinical 23 research coordination? 24 A. I would say somewhere between Page 23 1 four or seven years, somewhere in that 2 neighborhood. 3 Q. Like from 1985 to 1988 would 4 have been when he started? 5 A. Well, the end point certainly 6 wouldn't be that, no, '92 is when I came into it. 7 Q. Right, but he might have 8 started as early as 1985 or as late as 1988? 9 A. Right. I would say somewhere 10 in that ballpark. 11 Q. How about Mister Reis, when did 12 he begin as manager of clinical research 13 coordination? 14 A. He came later than Mister 15 Lightfoot, but I don't know the specific time 16 when he came in. 17 Q. Was anybody else a co-manager 18 of clinical research coordination before Mister 19 Reis came in? 20 A. No. 21 Q. Mister Lightfoot had those 22 duties exclusively? 23 A. That's correct. 24 Q. Then he had Mister Reis as -- I Page 24 1 assume they were co-managers? 2 A. Yes. 3 Q. And now they changed the 4 position back to where they only have one manager -- 5 A. Right. 6 Q. -- of clinical research 7 coordination; correct? 8 A. Right. 9 Q. You mentioned there was a 10 change in focus in connection with the 11 realignment of these duties into one individual 12 as opposed to two. Tell me what that change in 13 focus was. 14 A. Well, as we began to have more 15 studies that needed to be done, there was an 16 increased need to use outside contract research 17 organizations because we did not have capacity 18 internally to do as many studies. Therefore, we 19 needed to have someone take on that 20 responsibility. We also reduced some of the work 21 force, and so when some of those people began to 22 phase out, retire or transfer, then most of those 23 were not replaced. 24 Q. This didn't have anything to do Page 25 1 with the recent change in work force that we read 2 about a week or two ago at Lilly, did it? 3 A. No. 4 Q. Or was it a precursor to that? 5 A. Define precursor. 6 Q. Was there some semi-reduction 7 in work force in place in December, 1992, and 8 then there's been -- 9 A. No. 10 Q. -- since the new administration 11 has come in, a further reduction in work force? 12 A. No, this was really just a 13 business approach, business analysis, just to say 14 we can do some things differently. So it didn't 15 have anything at all to do with what's occurring 16 right now. 17 Q. What is it that's occurring 18 right now? 19 A. People are offered voluntary 20 retirement packages. 21 Q. Does -- and I hadn't even 22 thought about questioning you about this, but 23 since you mentioned it, does the current 24 reduction in work force involve the medical Page 26 1 division at Lilly research labs? 2 A. Well, the package has been 3 offered to individuals across the corporation. 4 I'm sure some folks in medical -- obviously 5 people in medical had that same opportunity as 6 will people in other areas. 7 Q. As I understand it, nobody is 8 currently being terminated in this most current 9 reduction in work force, but everybody -- or a 10 lot of individuals are given an opportunity to 11 take early retirement, plus there's going to be 12 some attrition occurring naturally; is that 13 right? 14 A. Yes, I'm not sure I am fully up 15 on all the background of that, all I'm aware of 16 is that we've got a voluntary retirement package, 17 and that we're not going to be adding people, 18 we're trying to reduce the overall work force. 19 Q. And I'm certainly not 20 attempting to get from you management positions 21 with respect to personnel managers, I'm just 22 wondering what your understanding is concerning 23 this reduction in work force and how it might 24 impact the division within which you're employed. Page 27 1 A. Okay. 2 Q. Are you -- have you been 3 offered some package? 4 A. I qualified for it, yes. 5 Q. And because you qualify, is 6 there any requirement that you avail yourself of 7 this opportunity? 8 A. Is there any requirement that I 9 avail myself -- say that again. 10 Q. Again, I'm not -- all I know 11 about it is what I glanced about and read about 12 in the paper, so the headlines says Lilly cuts 13 thirteen thousand people, but you read the fine 14 print and it may not be that at all, it may be -- 15 you know, you wouldn't -- as I understand it, 16 thirteen thousand people are not being axed from 17 Lilly at all. 18 A. No. 19 Q. That it's a much more 20 sophisticated and humane, possibly, cut. 21 A. Uh-huh. 22 Q. And my question is: Do you, 23 because you qualify for this early retirement 24 plan, have to exercise some particular type of Page 28 1 option? 2 A. No, I don't have to. 3 Q. Do you know of anybody in the 4 medical division that has been told that they 5 have to take the retirement option or be 6 terminated with their employment at Lilly? 7 A. No. 8 Q. Now you say primarily the 9 change in focus that has occurred recently since 10 December of 1992 was that the number of studies 11 that were necessary had increased, therefore 12 there was a situation where you couldn't handle 13 the administration of all of those studies 14 in-house, and needed to contract out some of 15 that; is that correct? 16 A. Yes. 17 Q. That is the change in focus 18 that's occurring -- 19 A. Right. 20 Q. -- within the clinical research 21 division; is that right? 22 A. Right. 23 Q. Have the number of studies 24 involving the chemical compound Fluoxetine Page 29 1 Hydrochloride increased? 2 MR. MYERS: Over what? 3 Q. Since 1987, when Prozac as used 4 for a treatment of depression was originally 5 approved by the Food and Drug Administration? 6 A. I couldn't specifically answer 7 that. 8 Q. All right. Are you familiar 9 with the clinical studies that are ongoing in the 10 psychopharmacology department? 11 A. Tangentially. 12 Q. All right. When you say 13 tangentially, why do you say only tangentially? 14 A. Well, because we have a lot of 15 studies that are ongoing. I'm aware of knowing 16 that we have studies that had begun prior to my 17 time, I'm aware of some of those. Some that are 18 occurring more frequently, I would know a little 19 bit more about. 20 Q. All right. 21 A. But I'm an administrator, and 22 not a technical person. 23 Q. I understand that, but part of 24 your administrative duties, I would assume, as Page 30 1 one who is the manager of coordination of 2 clinical research, would be being generally 3 familiar with what studies are going on with 4 respect to a particular compound, even though you 5 may not know specific details of any particular 6 study; is that correct? 7 A. Generally speaking. 8 Q. Approximately how many studies 9 are ongoing with respect to the compound 10 involving Fluoxetine Hydrochloride without regard 11 to whether or not they're for depression or for 12 some other usage? 13 A. I don't know that number. 14 Q. Is it more than one? 15 A. Yes. 16 Q. Is it more than ten? 17 A. I don't know. 18 Q. Do you have an opinion? 19 A. I just haven't done any 20 tabulation to look at that total number lately. 21 Q. Individuals who would do that 22 tabulation would be under your direction and 23 control, would they not? 24 A. I'm not sure, that's not a Page 31 1 focus. 2 Q. What do you mean it's not a 3 focus? 4 A. It's not a focus for my staff 5 to tabulate all of those studies that would 6 relate to Fluoxetine. 7 Q. Well, certainly somebody within 8 the Lilly research labs could do that, could they 9 not? 10 A. Yes, I am sure they could. 11 Q. Somebody is keeping up with 12 what studies are going on with respect to 13 Fluoxetine, aren't they? 14 A. Sure. 15 Q. Who would be generally aware or 16 most generally aware of what studies are 17 currently involving Fluoxetine? 18 A. I would say clinical research 19 administrators would know that. 20 Q. Clinical research 21 administrators? 22 A. Uh-huh. 23 Q. A clinical research 24 administrator would have duties with respect to a Page 32 1 particular investigation, would they not? 2 A. Right. 3 Q. Wouldn't there be somebody 4 looking over the overall picture and have their 5 finger on the pulse of all studies that are being 6 done with respect to Fluoxetine Hydrochloride? 7 A. Sure. 8 Q. Who would that be? 9 A. I would say it would be that 10 staff, the clinical research administrators' 11 staff and their management. 12 Q. Who would be the manager of 13 that staff at this time? 14 A. The paramedical side would 15 report up to Greg Brickler, Greg has department 16 heads that report to him, not managers, on that 17 function. 18 Q. Who would be the department 19 head that would be responsible for Fluoxetine 20 Hydrochloride ongoing clinical studies? 21 A. I think that would be Carol 22 Zapapas. 23 Q. What is her title? 24 A. Department head. Page 33 1 Q. Department head of what? 2 A. Well, it's in the medical 3 division, I don't know what the words are right 4 after that. 5 Q. All right. If somebody within 6 the Lilly organization proposed that an 7 additional study be done in connection with the 8 compound Fluoxetine Hydrochloride, would they not 9 have to come to you as the manager of clinical 10 research coordination in order to accomplish this 11 to some extent? 12 A. Yes. 13 Q. Has anybody come to you in 14 connection with a study to be done with respect 15 to Fluoxetine Hydrochloride since December, 1992, 16 when you became manager of the clinical research 17 coordination committee? 18 A. I'm aware of some, yes. 19 Q. Tell me about those studies 20 that you are aware of? 21 A. There was -- there more 22 recently was a study that had been proposed to 23 look at Fluoxetine in the treatment of 24 depression, but I couldn't recite to you what the Page 34 1 protocol specifics of that study were. 2 Q. Do you remember generally what 3 the purpose of that study was? 4 A. It was to look at Prozac in the 5 treatment of depression, certain symptoms in 6 depression. 7 Q. What symptoms? 8 A. Something called subsyndromal 9 syndrome. 10 Q. Sub -- 11 A. Syndromal. 12 Q. Subsyndromal syndrome? 13 A. Yes. 14 Q. That sounds like something I 15 might be diagnosed with, Mister Noone. Can you 16 give me an idea of what that is? 17 A. I really can't, no. 18 Q. Generally, what is your 19 understanding of what that is? 20 A. I really don't know that much 21 about what that is. 22 Q. Do you not have to know what it 23 is in order to coordinate the study? 24 A. No. Page 35 1 Q. That was -- that's a depression 2 study, as you understand it? 3 A. It has to do with depression, 4 yes. 5 Q. Do you know what subsyndrome -- 6 I can pick out parts of that, what subsyndrome 7 they were studying? 8 A. Subsyndrome. No, I don't, the 9 study hadn't started yet. 10 Q. Agitation, manic depression, 11 suicidality? 12 A. I'm not a technical expert, I 13 don't know the answer to that. 14 Q. Has that study started? 15 A. No. 16 Q. Is it scheduled to start? 17 A. It's planned, yes. I don't 18 know a date, though. 19 Q. Who is involved in doing this? 20 A. Who is involved in doing this. 21 Well, there are outside investigators who will be 22 involved in doing this. 23 Q. I understand that, but who 24 within the Lilly medical division, psycho -- Page 36 1 neuropsychopharmacology is planning this study? 2 A. Research physician, clinical 3 research coordinators would be helping in that. 4 Q. Which research physician? 5 A. John Heiligenstein. 6 Q. Any other research physicians 7 within medical that are involved in this in 8 addition to Dr. Heiligenstein? 9 A. He's a research physician for 10 that study. 11 Q. Who is the particular clinical 12 research administrator that's helping him on 13 that? 14 A. A lady by the name of Ellie 15 Schatz. 16 Q. Can you spell that for our 17 court reporter? I know exactly how to spell it, 18 but our court reporter may not. 19 A. Go ahead. 20 Q. No, I'm asking the questions 21 here. 22 A. I think it's S-C-H-A-T-Z. 23 That's close. 24 Q. Is it Ellie, E-L-L-E? Page 37 1 A. E-L-L-I-E. 2 Q. Do you know the names of any 3 other individuals that might be involved in 4 assisting Dr. Heiligenstein in this subsyndromal 5 syndrome in the depression study that's being 6 planned at this time? 7 A. Well, our people will be -- are 8 involved, will be involved, in setting up the 9 arrangements with the investigator sites. 10 Q. Specifically, who within your 11 group will be doing that? 12 A. Jim Waer, W-A-E-R, Brooks 13 Bradley and Joe Loehle. 14 Q. Can you spell that last name? 15 A. L-O-E-H-L-E. 16 Q. And what are their titles? 17 A. Clinical research coordinators. 18 Q. All right. So I don't know 19 that I heard the term clinical research 20 coordinators, I've heard clinical research 21 administrators. Is that two different functions? 22 A. Yes. 23 Q. Were there -- has there always 24 been a group of individuals who have been known Page 38 1 as clinical research coordinators within the 2 Lilly group? 3 A. Not always. 4 Q. Well, since 1980? 5 A. Yes. 6 Q. In what department have they 7 been in? 8 A. Clinical research coordination. 9 Q. Who is the head clinical 10 research coordinator, is there such a thing? I 11 know you're the -- 12 A. Manager. 13 Q. -- manager of that department, 14 but of the individuals actually coordinating 15 these things, is there a lead clinical research 16 coordinator? 17 A. I'm -- they report to me. 18 Q. And then they're all equal? 19 A. Yes. 20 Q. Are there any other clinical 21 research coordinators other than these three 22 individuals you just mentioned? 23 A. Yes. 24 Q. How many? Page 39 1 A. Nine more. 2 Q. Nine more? 3 A. Right. 4 Q. Are any of them -- well, can 5 you give me the names of any individuals who 6 would be currently or have in the past worked in 7 coordinating clinical studies involving 8 Fluoxetine? If they've never worked in 9 Fluoxetine, I'm not interested in knowing who 10 they are. 11 A. I would say all of them have. 12 Q. All right. Then I'm going to 13 need to ask you to give me their names. 14 A. Okay. Mario Savelloni. 15 Q. Spell the last name. 16 A. S-A-V-E-L-L-O-N-I. 17 Q. All right. 18 A. Art Zucker, Z-U-C-K-E-R, Fred 19 Cooley, C-O-O-L-E-Y, Ken Fluharty, F-L-H -- no, 20 F-L-U-H-A-R-T-Y, Chuck Lohman, L-O-H-M-A-N, 21 Charles Schalk, S-C-H-A-L-K, Cindy Larkin, 22 L-A-R-K-I-N, Glen Nolte, N-O-L-T-E, Tom Bratten, 23 B-R-A-T-T-E-N. How many is that? 24 Q. One, two -- nine in addition to Page 40 1 the three that you gave me. 2 A. Okay, that's it then. 3 Q. And all of these individuals 4 either are currently or have in the past worked 5 as clinical research coordinators in connection 6 with clinical trial studies done on Fluoxetine 7 Hydrochloride? 8 A. Yes, I would assume that they 9 all would have been involved at some point in 10 time. 11 Q. These clinical research 12 coordinators conduct clinical studies with 13 respect to other compounds Lilly has under 14 investigation, do they not? 15 A. That's correct. 16 Q. So there's not going to be any 17 misunderstanding, Fluoxetine Hydrochloride is 18 just one compound that has been under 19 investigation or is currently under investigation 20 by Eli Lilly and Company; is that correct? 21 A. Correct. 22 Q. And these clinical research 23 coordinators are in charge of coordinating 24 clinical research on all Lilly compounds, is that Page 41 1 correct, being investigated? 2 A. Generally speaking, yes, that's 3 true. 4 Q. In other words, it could be an 5 antibiotic? 6 A. Yes. 7 Q. It could be an insulin 8 derivative, it could be a psychotropic drug or 9 some other type of medication? 10 A. Right. 11 Q. Do any of these clinical 12 research coordinators have medical training at 13 all or are they strictly administrative? 14 A. Define medical training. 15 Q. Registered nurses, doctor of 16 osteopathy -- 17 A. Yes. 18 Q. -- chiropractors -- 19 A. Right. 20 Q. -- podiatrists, things of that 21 nature. 22 A. Right. 23 MR. MYERS: Pharmacists. 24 MR. SMITH: Pharmacists, good. Page 42 1 A. Majority of them are 2 pharmacists. 3 Q. All right. Do you know of any 4 of these other research coordinators that have 5 specialties such as statistics? 6 A. No. 7 Q. Systems programming, computer 8 sophisticated training? 9 A. Uh -- 10 Q. And by that I mean educated as 11 computer systems analyst -- 12 A. No. 13 Q. -- as opposed to becoming 14 conversely in connection with their job duties. 15 A. Really more the latter. 16 There's none that I can recall have had formal 17 systems training. 18 Q. Your formal educational 19 training is in chemistry? 20 A. Correct. 21 Q. Do you rarely apply your 22 chemical science degree to your day-to-day job 23 activities now? 24 A. Not in a strict sense, no. Page 43 1 Q. You told me about one 2 Fluoxetine study that's being planned. What 3 other Fluoxetine studies are ongoing that you're 4 aware of? 5 A. It seems like there's some 6 studies ongoing with Lovan. 7 Q. In what connection? 8 A. I think Lovan is the one that's 9 on the antiobesity side. 10 Q. Specifically, what studies are 11 being involved in the antiobesity side? 12 A. I really couldn't tell you more 13 than that. Those preceded, those were initiated 14 before I came into the job. 15 Q. Are those studies examining 16 anything in particular with respect to Lovan? 17 A. I couldn't tell you. 18 Q. Any other ongoing studies 19 involving the compound Fluoxetine Hydrochloride? 20 A. There may be, but none come to 21 mind. 22 Q. Who would you go to to ask what 23 is the current status of all Fluoxetine studies? 24 A. It might be Carol. Page 44 1 Q. Carol Zapapas? 2 A. Uh-huh. 3 MR. MYERS: Paul, off the record. 4 (DISCUSSION OFF THE RECORD.) 5 Q. Mister Noone, can you think of 6 any other ongoing studies involving Fluoxetine 7 Hydrochloride other than the two that you 8 mentioned? 9 A. As I indicated before, I can't. 10 Q. Are you familiar with the term 11 surveillance study? 12 A. I've heard the term, yes. 13 Q. Or seeing studies with 14 designation beginning with an S, like S oh oh 15 one, S oh oh two? 16 A. That does ring a bell. 17 Q. What is your understanding of 18 what a surveillance study is? 19 A. I'm not sure I can even answer 20 that. 21 Q. Are you familiar with the term 22 pilot study? 23 A. Pallet? 24 Q. Pilot. Page 45 1 A. Oh, pilot. 2 MR. MYERS: He talks funny. 3 A. Pilot study. I've heard the 4 term pilot used before, I'm not sure in what 5 frame we're talking about here, though. 6 Q. I'm talking about the framework 7 of any pilot studies in connection with 8 Fluoxetine Hydrochloride. At any time for any 9 reason, have you ever heard of a pilot study 10 involving the chemical compound Fluoxetine 11 Hydrochloride? 12 A. I don't know what studies we 13 may have applied the term pilot to that were done 14 in conjunction with the Fluoxetine study. 15 Q. Whether or not somebody else 16 has designated a particular term -- the 17 particular term pilot study to a particular 18 study, have you got an understanding of any pilot 19 studies which you're aware involving Fluoxetine 20 Hydrochloride? 21 A. Again, I can't relate to what 22 the term pilot would refer to in that in which 23 you've described. 24 Q. Well, how would you think -- Page 46 1 how would you describe a pilot study? 2 A. In my mind, the term pilot 3 might mean a first study, but I don't know how 4 it's applied in what you're referring to. 5 Q. You just don't think you've 6 ever heard that term -- 7 A. I've heard the term, but I've 8 also heard the term pilot probably mentioned in a 9 number of different settings, and I don't know 10 that there is a common definition to it. 11 Q. Whatever setting, have you 12 heard of a pilot study in connection with 13 Fluoxetine Hydrochloride? 14 A. I've heard the term pilot study 15 before, I can't relate to have I ever heard of 16 the term pilot study used in conjunction with any 17 Fluoxetine studies. 18 Q. Rechallenge. Are you aware of 19 any rechallenge studies in connection with 20 Fluoxetine Hydrochloride? 21 A. I am not. 22 Q. Never heard of a rechallenge 23 study involving Fluoxetine Hydrochloride? 24 A. I've never heard of any Page 47 1 specific rechallenge study related to Fluoxetine, 2 no. 3 Q. Any general rechallenge study 4 in connection with Fluoxetine Hydrochloride? 5 A. Somewhere along I may have 6 heard that term, but I could not relate it to any 7 study or any discussion of any study. 8 Q. Were you familiar that there 9 was a protocol submitted to the Food and Drug 10 Administration involving Fluoxetine Hydrochloride 11 whereby patients would be given Fluoxetine 12 Hydrochloride to determine whether or not their 13 reaction to the drug was the same as it had been 14 previously? 15 MR. MYERS: Before he answers, let me 16 object to the form. I think you're trying to 17 characterize what is in the protocol, and I think 18 it's inaccurate, you're assuming facts that are 19 not in evidence on the protocol. 20 Q. Well, I won't hold you to a 21 strict definition of what is actually in the 22 protocol, I'm trying to give you a description 23 generally of the concept of -- and specifically, 24 it's my understanding that there was a one-time Page 48 1 proposed, and formally submitted to the Food and 2 Drug Administration, protocol whereby individuals 3 who had experienced suicidal ideation or had 4 attempted suicide in the past would be 5 rechallenged with Fluoxetine again to see if that 6 particular adverse event reoccurred. 7 A. It's totally out of my 8 ballpark, I don't know anything about those 9 studies. 10 Q. You've never heard of that? 11 A. Oh, I may have heard somewhere 12 about it, but I don't -- I have -- if it was, 13 again, it was tangential and I don't even -- 14 other than the fact that maybe I heard the term, 15 I couldn't even tell you that there had been a 16 protocol that had been submitted on that to be 17 quite honest. 18 Q. Are you familiar with the term 19 validation study? 20 A. I probably -- well, I would 21 probably flunk a test if somebody asked me to 22 define what a validation study is. 23 Q. Well, I wasn't asking you to 24 define specifically what it is, but to answer Page 49 1 whether or not you're aware of any validation 2 studies in connection with Fluoxetine 3 Hydrochloride. 4 A. I'm not aware of validation 5 studies as pertains to Fluoxetine. 6 Q. Do you have a general idea of 7 approximately how many clinical studies are 8 ongoing at this time within Lilly research 9 laboratories in connection with investigation of 10 any particular drug by Lilly? 11 MR. MYERS: In the aggregate? 12 MR. SMITH: Yes, total. 13 Q. Since you're now the manager of 14 clinical research coordination, I thought you 15 might be able to give us an estimate of 16 approximately how many clinical studies are 17 ongoing by Lilly to investigate either existing 18 or new products. 19 A. I couldn't tell you that total 20 number of different studies. 21 Q. Can you give me approximately 22 how many studies there were? 23 A. I could give you approximately 24 the number of sites. Page 50 1 Q. All right. 2 A. And I would say that would be 3 somewhere that would be around three hundred -- 4 roughly around three hundred and sixty in the 5 U.S. 6 Q. How about outside the U.S.? 7 A. I have no idea. 8 Q. As manager of clinical research 9 coordination, does that include coordinating 10 clinical studies done outside the United States? 11 A. No. 12 Q. Who is involved in coordinating 13 the outside United States studies currently? 14 A. People in the international 15 areas. 16 Q. International areas? 17 A. Right. 18 Q. Such as? 19 A. People that would be in the 20 given country where the studies are ongoing would 21 be involved with that coordination. 22 Q. Wouldn't you or wouldn't 23 somebody here at Lilly research labs be familiar 24 with the number of studies being done on Lilly Page 51 1 products outside the United States? 2 A. Yes, I would say someone would. 3 Q. Who would be coordinating the 4 outside United States studies? 5 A. People in those countries would 6 be coordinating those studies, probably some were 7 coordinated from here as well. 8 Q. Of those that are coordinated 9 from here, who would be the individual who would 10 be doing that? 11 A. Probably would depend on the 12 type of study that was involved. 13 Q. Psychotropic drug. 14 A. It would depend on who the 15 person is who had responsibility for the given 16 drug. 17 Q. All right. Fluoxetine 18 Hydrochloride, who has responsibility for 19 Fluoxetine Hydrochloride in the United States? 20 A. John Heiligenstein. 21 Q. What is his title now? 22 A. He's a research physician, but 23 I couldn't tell you what his specific title is. 24 Q. Who is responsible for Page 52 1 Fluoxetine Hydrochloride coordination outside the 2 United States? 3 A. It could be John, if it's a -- 4 maybe a global study. 5 Q. All right. 6 A. And the only reason I say that, 7 I have only worked or I was only aware in working 8 with John recently on this sybsyndromal thing, so 9 I'm assuming he's got the responsibility for 10 Fluoxetine or for Prozac. 11 Q. Did he mention that this -- 12 that there were studies ongoing outside the 13 United States at this time in connection with 14 Fluoxetine Hydrochloride? 15 A. He did not mention that to me, 16 no. 17 Q. Did he envision the planned 18 sybsyndromal study to include individuals or 19 investigators who reside outside the United 20 States? 21 A. No. 22 Q. Is this study going to be an 23 in-house study or is this going to be a study 24 that you all are going to contract out? Page 53 1 A. This is planned to be an 2 in-house study. 3 Q. All right. Has a protocol been 4 drawn up yet on that study? 5 A. It's my understanding that it 6 has been, yes. 7 Q. Has it been submitted to the 8 Food and Drug Administration? 9 A. I don't know yet. 10 Q. Is it planned to be submitted 11 to the Food and Drug Administration? 12 A. Definitely. 13 Q. This is a study that's 14 definitely going to be done? 15 A. That's the plan, yes. 16 Q. When is it going to start? 17 A. I believe we targeted it 18 somewhere before the end of this year, to start, 19 but I couldn't tell you the specific date. 20 Q. Targeted before the end of 21 1993? 22 A. To start, yes. 23 Q. And how long is it scheduled to 24 last? Page 54 1 A. It's difficult to totally 2 project in light of how long -- the limiting 3 factor will be enrollment of patients, but 4 somewhere in the neighborhood of probably a year 5 to two years, somewhere in that ballpark. 6 Q. How many particular patients 7 are going to be involved or enrolled, I guess, is 8 the better term? 9 A. I don't remember now what 10 numbers they were talking about. 11 Q. Approximately? 12 A. I don't remember. 13 Q. How many sites are going to be 14 involved? 15 A. Three. 16 Q. Where are those sites going to 17 be? 18 A. One in Texas, one in 19 Pittsburgh, and one in the Los Angeles area. 20 Q. Where in Texas? 21 A. I think it's in Dallas, but I'm 22 not sure. I think it's Dallas, though. 23 Q. Have you hired an investigator 24 for the Dallas area yet? Page 55 1 A. We have talked to an 2 investigator there, I don't know whether the 3 contracts have been signed at this point. 4 Q. Who is that individual? 5 MR. MYERS: He's not going to tell you 6 that, Paul, he's not going to tell you who the 7 investigators are. Ask him anything -- 8 MR. SMITH: I thought he might. 9 MR. MYERS: Excuse me? 10 MR. SMITH: I thought he might. 11 MR. MYERS: No, he's not. 12 Q. Without telling me the name, do 13 you currently know who it is? 14 MR. MYERS: You can answer that. 15 A. Yes, I do. 16 Q. Have you talked with this 17 individual? 18 A. No. 19 Q. Has Doctor Heiligenstein, that 20 you know of, talked to the individual? 21 A. I don't know whether he has 22 talked directly to him or not. 23 Q. Who within Doctor 24 Heiligenstein's group would have been the Page 56 1 individual that would have been selecting the 2 Dallas investigator? 3 A. Doctor Heiligenstein would have 4 had involvement with that or our clinical 5 research coordinator would also. 6 Q. Who would be the clinical 7 research coordinator? 8 A. Mister Bradley. 9 Q. Brooks Bradley? 10 A. Uh-huh. 11 MR. MYERS: Yes. You need to say yes, 12 Mike, so she can take it down. 13 A. Yes, Brooks Bradley. 14 Q. This Dallas investigator is 15 planned to be doing an investigation with respect 16 to Fluoxetine Hydrochloride in depressed 17 individuals, is he not? 18 A. It relates to depression, but I 19 don't know that that's the -- 20 Q. It's some subsyndrome -- 21 A. What I indicated was 22 sybsyndromal, right. 23 Q. But the depressed individuals 24 are going to be the individuals that are the Page 57 1 subjects of the investigation and a particular 2 group of depressed individuals? 3 A. The subject of that are those 4 patients that have the sybsyndromal syndrome. 5 Q. What is that sybsyndromal 6 syndrome? 7 A. I don't know, I can't define 8 that. 9 Q. Suicidality? 10 A. I can't define it. 11 Q. Have you ever talked with 12 Doctor Heiligenstein about suicidality or the 13 issue of suicidality being involved in this 14 particular study? 15 A. No, I have not. 16 Q. Has suicide ever come up in 17 connection with discussions of this study? 18 A. No. 19 Q. Can you say specifically that 20 this study is not going to investigate 21 suicidality at all? 22 A. All I can tell you is this 23 study is going to look at sybsyndromal syndrome. 24 Q. But you don't know what that Page 58 1 is? 2 A. Right. 3 Q. And can't give me any 4 description or any help -- 5 A. I indicated earlier that it 6 relates to depression. 7 Q. So it's a depression study? 8 A. No, it relates to depression, 9 it relates to some of the symptoms of depression, 10 but that's all I can tell you. 11 Q. Who is that individual, who is 12 that investigator in Dallas that is being -- that 13 you're discussing this with? 14 MR. MYERS: I'm going to instruct him 15 not to answer that. 16 MR. SMITH: Can you give me the basis 17 of your instruction, what is your objection to 18 the -- 19 MR. MYERS: Information is proprietary, 20 and is otherwise governed by certain federal 21 regulations, and it's probably governed by 22 several court orders in place in the MDL and the 23 Fentress case. 24 MS. ZETTLER: What other federal Page 59 1 regulations? 2 MR. MYERS: Look under section -- look 3 under 21 CFR under the three hundred series, I 4 can't quote you any further than that. 5 MS. ZETTLER: What does that regulation 6 say, in essence? 7 MR. MYERS: I can't quote a chapter or 8 verse to you. 9 MS. ZETTLER: You can paraphrase it. 10 MR. MYERS: I'm not testifying here -- 11 MS. ZETTLER: I'm not asking you to 12 testify, Larry, I'm asking you to give me the 13 basis of your objection. 14 MR. MYERS: I've given you the basis, 15 that it is proprietary information, that it is 16 awfully remote in time to any of the events that 17 are the subject of any of the cases that we're 18 here on today, and disclosure of that information 19 is governed by the federal regulations. And 20 that's all I'm going to say about it. You can 21 ask him anything you want about the study, but 22 he's just not going to tell you who the 23 investigators are. 24 MS. ZETTLER: Well, the proprietary Page 60 1 objection has been eliminated by Judge Potter in 2 the Fentress case in which this deposition has 3 been ordered and agreed upon as you say. 4 MR. MYERS: I think the last time we 5 were there, when this subject came up, he said 6 that that was something that a motion would need 7 to be filed on, and he would take it up. 8 MS. ZETTLER: No, actually what he said 9 is that there was no trade secret or proprietary 10 commercial information or objection at this point 11 as far as that kind of information goes, and that -- 12 so you can no longer use that objection. As far 13 as remoteness in time, that has absolutely no 14 basis -- there's absolutely no basis for an 15 objection in a discovery deposition, and you know 16 it. This study for all we know could be a study 17 directly related to suicidality or violent 18 aggressive behavior, and remoteness has 19 absolutely nothing to do with it. 20 MR. MYERS: The witness can tell you 21 just about anything he knows about the study, but 22 he's not going to tell you the investigators, and 23 there's no reason to argue about it. 24 MS. ZETTLER: Okay, we'll bring him Page 61 1 back when Judge Potter rules to ask him the 2 questions specifically -- we'll ask for 3 sanctions. 4 MR. MYERS: I wouldn't count on it. 5 Just ask him another question, anything you want 6 about the study. 7 Q. What's the name of the 8 investigator in Los Angeles? 9 MR. MYERS: He's not going to tell you 10 that either. 11 Q. What's the name of the 12 investigator in Pittsburgh? 13 MR. MYERS: Same objection. 14 MS. ZETTLER: Certify all those 15 questions. 16 (QUESTIONS CERTIFIED.) 17 Q. Do you know whether the study 18 contemplates in-patient or out-patient treatment? 19 A. I don't know. 20 Q. Do you know whether or not this 21 study excludes or includes individuals who are a 22 serious suicidal risk, as that term has been used 23 in previous protocols in connection with 24 Fluoxetine Hydrochloride? Page 62 1 A. I don't know, I have not read 2 the protocol. 3 Q. You know the areas of protocol 4 that have been prepared, though? 5 A. Say that again? 6 Q. You know a protocol has been 7 prepared in connection with this study? 8 A. Yes. 9 Q. And I assume that Doctor 10 Heiligenstein would have that protocol; is that 11 correct? 12 A. Yes, he would have access to 13 it. 14 Q. And I would assume that Mister 15 Bradley probably has that protocol? 16 A. I would assume he would, yes. 17 Q. He would need that information 18 in order to contact these investigators or to 19 coordinate the study? 20 A. Unless Doctor Heiligenstein had 21 talked to the physician directly. 22 Q. What is Mister Bradley's -- 23 what are Mister Bradley's duties in connection 24 with this particular study, at this time? Page 63 1 A. He would work with the site, 2 work through the budget negotiation, what it's 3 going to cost, setting up the expectations of 4 what will need to be done, assuring that the site 5 would be able to meet all the obligations in 6 meeting the protocol, and assuring that they're 7 complying with regulations as well. 8 Q. Did you say you had seen this 9 protocol? 10 A. No, I didn't, I said that I had 11 not seen it. 12 Q. Do you recall in your 13 discussions with Doctor Heiligenstein or Mister 14 Bradley any particular necessity for any 15 particular exclusion or inclusion of depressed 16 individuals? 17 A. No, I don't. 18 Q. You follow what I'm saying, was 19 it planned that particular individuals were going 20 to be studied over other individuals? I'm trying 21 to get as much knowledge as you have about what 22 this study is, and I'm fishing for different ways 23 to get it. 24 A. I understand that, but I'm back Page 64 1 to where I was before. Other than the fact I 2 know it was a study to look at subsyndromal 3 syndrome, I really can't give you -- don't know 4 any information. 5 Q. Do you know whether or not this 6 study is going to have any measure of whether or 7 not an individual's depression gets worse or 8 better? 9 A. It would look at the 10 subsyndromal syndrome to determine whether 11 patients get better or not get better. 12 Q. What type of test or scales are 13 going to be administered to the patients to 14 measure this? 15 A. I don't know. 16 Q. You're familiar with the 17 Hamilton Depression Scale? 18 A. I know of the Hamilton 19 Depression Scale. 20 Q. Do you know whether or not 21 that's going to be used in connection with the -- 22 A. I don't. 23 Q. Do you know whether the -- 24 whether or not any suicidal ideation scales are Page 65 1 going to be involved? 2 A. I do not. 3 Q. You haven't seen any type of 4 tests that are going to be administered? 5 A. No. 6 Q. This syndrome, is this a 7 psychological or physiological syndrome? 8 A. I don't know. 9 Q. Is this syndrome a syndrome 10 that has to do with individuals who have a 11 particular physical reaction to an increase or 12 decrease in seratonin? 13 A. I don't know. 14 Q. Have you had any discussions 15 concerning this study with Mister Brickler, your 16 supervisor? 17 A. Yes. 18 Q. Tell me about those discussions 19 that you have had in connection with these 20 studies with Mister Brickler. 21 A. It had to do with the cost of 22 the study. 23 Q. What is approximately the 24 estimated cost of the study? Page 66 1 MR. MYERS: Don't tell him that, that's 2 proprietary how much we spend on studies. 3 MS. ZETTLER: I'll certify it. 4 (QUESTION CERTIFIED.) 5 Q. Any other subject of this study 6 in this discussion between you and Mister 7 Brickler? 8 A. That seemed like that was the 9 focus, as I recall, of the discussion. 10 Q. Is it required that you submit 11 some type of budget proposal on each proposed or 12 planned study? 13 A. I don't personally know. 14 MR. MYERS: Submit to who, Paul? 15 MR. SMITH: To anybody. 16 A. I don't submit it to anybody. 17 Q. In connection with your job as 18 manager of clinical research coordination, does 19 that -- does a part of that involve the budgetary 20 aspects of these clinical studies? 21 A. Yes, it does. 22 Q. Who prepares those budgets for 23 you within your group? 24 A. It isn't always done the same Page 67 1 way. Typically the clinical research coordinator 2 or a clinical research coordinator and a 3 physician, and probably a CRA, would begin to 4 work with that. 5 Q. Once the budget is formulated, 6 it would go to you, come to you? 7 A. No, it would -- well, the 8 initial budget would normally go back out to the 9 clinical research coordinator. 10 Q. But do you have to approve a 11 budget on a particular proposed study or does 12 budget approval go into some other chain of 13 command? 14 A. It would go -- yes, it would 15 not be approved by me. 16 Q. Who would approve the budget? 17 A. The grants committee would do 18 that. 19 Q. Who is the head of the grants 20 committee? 21 A. I believe that's Michael 22 Hanson. 23 Q. What is his job title? 24 A. He's the vice-president in Page 68 1 medical. 2 Q. Is he an M.D. or is he a bean 3 counter type person? 4 MR. MYERS: Or none of the above. 5 Q. No, I just -- either one of 6 those. 7 MR. MYERS: It doesn't have to be 8 either one of those, Mister Noone, it could be 9 something else. 10 A. No. 11 Q. What is he? 12 A. What? 13 Q. What is his training? 14 A. He's a pharmacist. 15 Q. Let's go back to these outside 16 U.S. studies for a minute in connection with your 17 current duties as manager of clinical research 18 coordination. As I understand it, you currently, 19 as manager of clinical research coordination, 20 coordinate only United States studies; is that 21 right? 22 A. Yes. 23 Q. And Lilly has for years, in 24 connection with many projects -- products, and Page 69 1 compounds, studied their drug in different 2 countries other than the United States? 3 A. That's true. 4 Q. And data from those studies is 5 used in connection with deregulatory approval 6 process of a particular compound; correct? 7 A. Yes. 8 Q. And adverse events in 9 connection with -- that arise during those 10 studies have to be reported to the Food and Drug 11 Administration, do they not? 12 A. Yes. 13 Q. As 1639s; correct? 14 A. Go back and ask the question 15 again. 16 Q. These adverse events that occur 17 in international, outside the U.S. clinical 18 studies, have to be reported to the United States 19 Food and Drug Administration as adverse events 20 for the particular drug, and a 1639 has to be 21 submitted for an adverse event occurring in an 22 international clinical study, do they not? 23 A. I don't recall that they all 24 are required to be put on to a 1639. Page 70 1 Q. If there is a requirement that 2 a 1639 be generated by Eli Lilly and Company, it 3 doesn't make -- if that adverse event meets the 4 requirement, it doesn't make any difference 5 whether that adverse event occurred within the 6 United States or outside the United States, it's 7 got to be reported to the Food and Drug 8 Administration if Lilly knows about it, doesn't 9 it? 10 A. That's correct. 11 Q. So, there have -- what I'm 12 wanting to know is what kind of coordination is 13 going on with the outside U.S. clinical studies 14 that are being done by Eli Lilly and Company, is 15 there not one individual that is coordinating all 16 the outside United States clinical studies being 17 done? 18 MR. MYERS: In a job function like his? 19 MR. SMITH: Yes. 20 Q. You say you're only 21 coordinating in U.S. studies. Isn't there 22 somebody coordinating outside U.S. studies? 23 A. Things are just done 24 differently in different parts of the world. All Page 71 1 functions that you have in one country are not 2 duplicated in other countries. 3 Q. I understand that. Regardless 4 of that, isn't somebody coordinating the progress 5 of those studies that are occurring outside the 6 United States? 7 A. Yes -- 8 Q. Who is that? 9 A. -- the people would be doing 10 that. It would depend on the study and where the 11 study is done. 12 Q. Let's say there's a study being 13 done in Great Britain today on depression, and 14 it's examining individuals who are depressed and 15 they're being administered Fluoxetine 16 Hydrochloride -- some of them are being 17 administered Fluoxetine Hydrochloride, some of 18 them are being administered a comparitor drug, 19 and some of them are being administered a 20 placebo. 21 A. Uh-huh. 22 Q. Would there be anybody in 23 Indianapolis who would be knowledgable concerning 24 that particular study that's going on? Page 72 1 A. It would depend on the study. 2 If it's just a local generated study, then that 3 would be almost exclusively done by the local 4 country. If it's something we've got more 5 interest in from a global standpoint, then we 6 might have somebody else dealing with that. 7 Q. I'm talking about a study 8 that's being funded by Eli Lilly and Company, 9 that they're paying the investigator, they're 10 supplying the medication. 11 A. Right. 12 Q. Who in Indianapolis is 13 reviewing those studies that are being funded by 14 Eli Lilly and Company that are occurring outside 15 the United States? 16 A. From a funding standpoint or 17 what are you talking about? 18 Q. From a coordination standpoint. 19 A. It depends on what is being 20 coordinated. 21 Q. All right. Such as, give me an 22 example. 23 A. If it's budgets, that's going 24 to be another -- that's a different question Page 73 1 that's being asked, that could be funded and 2 handled completely locally, or it could be funded 3 and handled here in the United States as the 4 corporate headquarters. 5 Q. How about coordinating the 6 results of that study, the signs, the results of 7 that study? 8 A. What's the question then? 9 Q. Would that be coordinated here 10 in the United States or would that be coordinated 11 in a particular country? 12 A. Both. 13 Q. Could Lilly fund a study in 14 Great Britain and leave all the coordination up 15 to the individuals at Great Britain that -- I 16 assume Lilly has an affiliate in England? 17 A. Yes. 18 Q. What's the name of that 19 affiliate? 20 A. It's the UK affiliate. 21 Q. Could that all be left 22 completely to the UK affiliate? 23 A. I'm sorry, give me the question 24 again. Page 74 1 Q. Could that clinical study be 2 left completely within the purview of that 3 British affiliate? 4 A. If they're wanting to do the 5 study locally? 6 Q. Right. 7 A. Yes, they would initiate and 8 coordinate that. 9 Q. What reporting would they do in 10 connection with reporting the results of that 11 study, the progress of that study, and adverse 12 events that occurred during that study to the 13 appropriate individuals at Eli Lilly and Company 14 in Indianapolis, Indiana? 15 A. They would be obligated to 16 fulfill all the regulatory requirements, not just 17 for the FDA, but for the rules of England as 18 well, and that would be established as they do 19 the study. 20 Q. Does that mean that even though 21 that study was funded -- even though that study 22 was coordinated and conducted in England, that a 23 protocol would have to be submitted to the Food 24 and Drug Administration in the United States? Page 75 1 A. Would a protocol have to be 2 submitted, I don't know that it has to be in all 3 cases, I don't remember. 4 Q. Well, you've been with 5 regulatory affairs at Lilly since 1985, have you 6 not? 7 A. I was in regulatory affairs 8 since 1988. 9 Q. Before that you were a 10 department head in -- 11 A. Medical information services, 12 doing regulatory stuff. 13 Q. Medical regulatory services. 14 And that had to do with complying with FDA 15 regulations. 16 A. It had to do with that, yes. 17 Q. What I'm asking you: Would a 18 study such as I've described, where it was going 19 to be done completely in England, completely on 20 English subjects, studying Fluoxetine 21 Hydrochloride, would the protocol for that study 22 have to be submitted to the Food and Drug 23 Administration? 24 A. I really don't remember. Page 76 1 Q. Would it have to be -- of 2 course, I guess anything that's submitted to the 3 FDA either becomes a part of the NDA or IND at 4 the FDA, does it not? 5 A. Give me the question again. 6 Q. Let me change it up a little 7 bit. Is there any documentation that is 8 submitted to -- from Eli Lilly and Company in 9 connection with an Eli Lilly and Company drug 10 that is submitted to the Food and Drug 11 Administration that doesn't become a part of 12 either the IND or the NDA with respect to that 13 particular drug? 14 A. Anything -- say it one more 15 time, I'm having a little trouble focusing on 16 this question. 17 Q. Do you need to take a break or -- 18 I don't want you -- 19 A. No, I'm just having trouble 20 tracking your question. Run it by me one more 21 time. 22 Q. If Lilly submits something to 23 the Food and Drug Administration -- 24 A. Okay. Page 77 1 Q. -- in connection -- well, let's 2 be specific, in connection with the compound 3 Fluoxetine Hydrochloride. 4 A. Okay. 5 Q. Does it necessarily become, 6 within the IND, filed -- I mean become, within 7 the FDA, filed with either the IND or the NDA on 8 Fluoxetine Hydrochloride? 9 A. Okay. I would say yes. 10 Q. That's if Lilly submits it to 11 the Food and Drug Administration, it becomes part 12 of the IND or NDA? 13 A. Yes. 14 Q. In connection with the 15 particular drug it pertains to; correct? 16 A. Right -- well, wait a minute. 17 Did you take it beyond prescription drugs at this 18 point? 19 Q. No, I'm speaking only of 20 prescription drugs. 21 MR. MYERS: And you're speaking of 22 Fluoxetine. 23 Q. I'm talking about it as a 24 compound. I said assume once the compound is -- Page 78 1 an IND is submitted on a particular compound, 2 then there are particular regulations that follow 3 that compound throughout its life, whether it's 4 being studied for depression, weight control or 5 baldness, right? 6 A. Right. 7 Q. So is the answer to my question 8 that it does become a part of either the IND or 9 NDA? 10 A. That's correct. 11 Q. Now if you have an 12 international study that's created exclusively 13 within an international affiliate -- 14 A. Right. 15 Q. -- do you have to report that 16 study, the existence of that study, to the Food 17 and Drug Administration? 18 A. If the regulations stipulate it 19 so, yes, you do. 20 Q. I don't understand. 21 A. Well, I have been out of the 22 regulatory job since last December, and I was not 23 a technical expert anyway, so -- but we obviously 24 have a need, anytime that there is a regulation Page 79 1 to fulfill those needs of the regulation, 2 therefore if we're doing a study overseas, and 3 the IND and/or NDA regulations require us to 4 provide that information, we do. 5 Q. But you don't know whether the 6 regulations require -- you don't know what the 7 regulations require with respect to what has to 8 be reported to the Food and Drug Administration, 9 is that what you're saying? 10 A. I couldn't recite all of that 11 because there are differences across different 12 types of studies, and I'm not really up to speed 13 on all that at this point. 14 Q. Are you familiar with a study 15 that was done in Taiwan in connection with 16 Fluoxetine Hydrochloride? 17 A. No. 18 Q. Have you ever heard of a study 19 that occurred in Taiwan involving Fluoxetine 20 Hydrochloride? 21 A. I can't say that I have, no. 22 Q. Do you know whether or not 23 there is an ongoing study occurring in Taiwan in 24 connection with investigation of Fluoxetine Page 80 1 Hydrochloride for any purpose? 2 A. I'm not aware of any such 3 study. 4 Q. So as of today, on October 5 19th, 1993, as manager of clinical research 6 coordination, it's your testimony that you are 7 not aware of a study that has been done in Taiwan 8 with respect to Fluoxetine Hydrochloride in the 9 past? 10 A. That's correct. 11 Q. And as the manager of clinical 12 research coordination today, on October 19th, 13 1993, you're not aware of a study currently 14 involving Fluoxetine Hydrochloride? 15 MR. MYERS: In? 16 MR. SMITH: Taiwan. 17 A. No. 18 Q. Either as the drug being 19 investigated or as a comparitor drug? 20 A. That's correct. 21 Q. If there were a study being 22 done in Taiwan today, that's funded by Lilly, who 23 would be coordinating that study since it's an 24 international study? Page 81 1 MR. MYERS: When you say funded by 2 Lilly, you mean Lilly here in the States or maybe 3 the Lilly affiliate, or are you drawing a 4 distinction? 5 MR. SMITH: Either one. 6 Q. Well, let's break it down into 7 two questions. Does the fact that it's -- that a 8 particular study might be funded in the United 9 States but done outside the United States, versus 10 funded and done outside the United States, have 11 any impact with respect to whether or not you 12 will coordinate that study as the manager of 13 clinical research coordination? 14 A. I have nothing to do with 15 studies done outside the United States. 16 Q. But it's your testimony here 17 that you don't know of anybody that does have 18 anything to do with studies done outside the 19 United States; is that correct? 20 MR. MYERS: I object to the form, 21 that's not what he said. 22 Q. What did you say? 23 A. I said I do not coordinate 24 studies outside the United States, which was in Page 82 1 reference to your other question, the one you 2 just repeated. 3 Q. Who does coordinate studies 4 outside the United States? 5 A. It would depend on whether or 6 not they would be coordinated locally, and they 7 would also be coordinated from our corporate 8 headquarters here. 9 Q. What would be the determination 10 with respect to whether or not they would be 11 coordinated locally or here at Indianapolis? 12 A. I'll answer generally that 13 there may be a specific need locally to do a 14 study in which case no one else may be 15 interested. And if we're coordinating it from 16 our corporate headquarters, the logic there would 17 be that it would be a study that would be of 18 interest in different parts of the world. 19 Q. So who here would coordinate 20 it, here in Indianapolis? 21 A. Well, it would be whichever 22 physician has that responsibility for Fluoxetine, 23 both inside and outside the United States. 24 Q. Who is that now? Page 83 1 A. I mentioned earlier I thought 2 that it might be John Heiligenstein, but the 3 study we talked about earlier was strictly a 4 study done here in the U.S., so I'm not sure that 5 he was the physician that handles the worldwide 6 coordination. 7 Q. And if it's coordinated outside 8 the United States, it would be coordinated by 9 somebody within the outside affiliate, within the 10 outside affiliate? 11 MR. MYERS: Where the study was going 12 on. 13 MR. SMITH: Yes. 14 A. Generally, that's true. 15 Q. Do you know of exceptions? 16 A. The only reason I say that is 17 that we are constantly in reorganizational mode 18 and -- 19 Q. I noticed that. 20 A. And it could have been that 21 there could have been a European study 22 coordinated outside of our facility in the UK, 23 which also serves as a coordination site for 24 Europe. Page 84 1 Q. Where is that? 2 A. That would be in Erl Wood, 3 England. 4 Q. And Erl Wood coordinates all 5 your European studies? 6 A. Well, I'm not sure where they 7 are at this point, there's been a good bit of 8 decentralization efforts, so I'm not sure that I 9 could even tell you where that is right now, I'm 10 too far removed from the international scene. 11 Q. Who is the clinical research 12 physician at Erl Wood? 13 A. I don't know. 14 Q. Do you know of anybody, any 15 clinical research physician that's been at Erl 16 Wood? 17 MR. MYERS: For Fluoxetine? 18 MR. SMITH: Yes. 19 A. I don't remember who was 20 involved with Fluoxetine there. 21 Q. With respect to adverse events 22 that occurred during an international clinical 23 study, would there be anybody in Indianapolis who 24 would coordinate the compilation of those adverse Page 85 1 events that occurred during a particular clinical 2 study done internationally? 3 A. Give me the question one more 4 time? 5 MR. SMITH: I'm going to have to have 6 that read back. 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED TESTIMONY.) 9 A. At the time of the periodic 10 reports that are required by the FDA, individuals 11 would sit down and look at the data base and look 12 at what's required to be reported to the FDA. 13 That's apart from the alert 1639s that are 14 submitted, that they would look at all the global 15 data of anything that is required to be submitted 16 by law, and then that would be submitted. 17 Q. I guess maybe my question is: 18 Does Lilly require that they be made aware of any 19 adverse events here in Indianapolis that might 20 occur in an international clinical trial? 21 A. All serious events have to be 22 reported in Indianapolis or are required to be 23 reported in Indianapolis. 24 Q. By the international affiliate? Page 86 1 A. That's correct. 2 Q. And the international affiliate 3 gives the particular investigator at the 4 particular site, internationally, instructions to 5 report any adverse events that occur? 6 A. Any serious adverse events. 7 Q. Serious adverse events. 8 A. Right. In a study, which is 9 what you are talking about. 10 Q. Is there any requirement that 11 all clinical report forms be submitted by the 12 international investigator to the local 13 affiliate, and then to Lilly here in 14 Indianapolis? 15 A. Say it -- give me the term 16 again, clinical report form? 17 Q. Yes, CRFs. 18 A. All right. You're talking 19 about CRFs, not 1639s. I'm not familiar with 20 that particular requirement, because it seems to 21 me that the rules are different prior to your 22 ending a submission than they are afterwards. 23 Q. All right. You mean you're 24 saying that maybe you had a Phase 4 study done Page 87 1 after market approval, but you maybe had an 2 ongoing study or started a new study -- 3 A. Yes. 4 Q. -- and you might not have to 5 submit the same clinical report forms that you 6 would if approval was still pending? 7 A. Yes. I really would have to go 8 back and revisit those regulations again because 9 I think they are -- it's not abundantly clear 10 from my end at this point what the specifics of 11 them are. 12 Q. There's no difference in United 13 States studies, though, on reporting clinical 14 report forms to the FDA, whether it be pre or 15 post market approval, all clinical report forms 16 do have to be submitted to the Food and Drug 17 Administration, do they not? 18 A. I don't recall that that's the 19 case, no. 20 Q. As the manager of clinical 21 research coordination, do you know whether or not 22 Eli Lilly is investigating any other compounds 23 for treatment of depression? 24 A. Do I know if we are? Page 88 1 Q. Yes. 2 A. Yes. 3 Q. And are they -- are they? 4 A. Are we? 5 Q. Yes, are you? 6 A. Yes. 7 Q. What are the names of those 8 compounds? 9 MR. MYERS: He's not going to tell you 10 that, Paul, that's proprietary. And I think 11 whether they're doing it is certainly 12 decoverable, and whether it's an antidepressant 13 is discoverable, but he's not going to tell you 14 what the compounds are, that's proprietary and 15 I'm going to instruct him not to answer that. 16 Q. Has an IND or NDA been 17 submitted in connection with these compounds? 18 A. Yes. 19 Q. When? 20 A. I don't know. 21 Q. This year? 22 A. I don't know the timing, I just 23 know that we have studies that have been 24 occurring, therefore we would have submitted an Page 89 1 IND. 2 Q. On new antidepressant 3 compounds? 4 A. Correct. 5 Q. And do you know whether or not 6 these new antidepressant compounds are a specific 7 seratonin reuptake inhibitors? 8 A. I don't. 9 Q. Do you know what I mean by 10 SSRI? 11 A. I know that there are two or 12 three compounds out on the market today that have 13 that attribute associated with them, yes. 14 Q. Fluoxetine Hydrochloride being 15 one? 16 A. Right. 17 Q. Prozac being one. My question 18 to you is: There apparently, since there are 19 several, at least two, maybe three other 20 seratonin specific reuptake inhibitors on the 21 market, there apparently is different chemical 22 formulas that can affect production of seratonin; 23 correct? 24 A. Apparently. Page 90 1 Q. My question is: Is this 2 compound that's being investigated by Lilly, and 3 an IND or NDA has been submitted on this new 4 antidepressant compound, do you know whether or 5 not it is a seratonin specific reuptake 6 inhibitor? 7 A. I don't know for sure. The one 8 I'm thinking of, I don't think is, but I haven't 9 been involved in discussions on the science of 10 it, that's only an impression. 11 Q. Who is the clinical research 12 physician that is involved in the investigation 13 of that new compound? 14 A. Atuhl Pande, A-T-U-H-L, 15 P-A-N-D-E. 16 Q. Where is he located? 17 A. Indianapolis. 18 Q. What is his title? 19 A. He's a research physician, I 20 don't know the specific title. 21 Q. And do you know who Doctor -- 22 is he an M.D.? 23 A. Correct. 24 Q. Do you know who his supervisor Page 91 1 is or who he reports to? 2 A. I believe that would be Gary 3 Tollefson. 4 Q. And do you know how many 5 clinical studies have been done in connection 6 with this new compound? 7 A. I don't know offhand, no. 8 Q. Do you know what phase the 9 clinical research is in, one, two, three or four? 10 A. Phase 2. 11 Q. So that involves human studies, 12 does it not? 13 A. That's correct. 14 Q. And is this compound a -- do 15 you know -- I believe you said that you didn't 16 think it was an SSRI? 17 A. Right. 18 Q. Do you know whether or not it 19 is a tricyclic or a MAO or a combination or can 20 you give me any insight into that? 21 A. I don't know anything about the 22 science or chemistry of it. 23 Q. Is Fluoxetine Hydrochloride 24 being used as a comparitor drug in any of the Page 92 1 ongoing studies in connection with this new 2 compound? 3 A. Not that I'm aware of. 4 Q. Who would be most knowledgable 5 concerning that issue? 6 A. Probably the physician. 7 Q. Doctor Pande? 8 A. Uh-huh. 9 MR. MYERS: Yes. 10 A. Yes. 11 Q. Do you know whether or not any 12 of these studies on this new compound, new 13 antidepressant compound, are being done outside 14 the United States? 15 A. I don't know. 16 Q. Are the clinical trials that 17 are being done in connection with the new 18 antidepressant compound being included within the 19 global tracking system? 20 A. I would assume that they would 21 be. 22 Q. Who is in charge of the global 23 tracking system now? 24 A. For this compound? Page 93 1 Q. No. As I understand it, global 2 tracking system is a computerized data base. 3 A. You're talking global project 4 tracking, I'm sorry. There's a lot of different 5 tracking systems. 6 Q. We're going to talk about those 7 after lunch. I want you to have a full belly 8 before we start talking about that. 9 A. Okay, I'll look forward to 10 that. 11 MR. MYERS: What's the question? 12 MR. SMITH: I don't have any idea. 13 MR. MYERS: I thought it was who was in 14 charge. 15 Q. Who was in charge of the global 16 thing? 17 MR. MYERS: Global project tracking? 18 MR. SMITH: Thank you. 19 A. Global project tracking resides 20 in the medical regulatory affairs area. 21 Q. And who is in charge of that? 22 A. Max Talbott is director of 23 medical regulatory affairs. 24 Q. You were in charge of that Page 94 1 before you left? 2 MR. MYERS: That what? 3 Q. As director of medical 4 regulatory affairs. 5 A. No, I was not director of 6 medical regulatory affairs, I was manager. 7 Q. Manager? 8 A. Yes. 9 Q. As manager -- 10 A. It did report to me, correct, 11 yes, the coordination function. 12 Q. Who was it that was reporting 13 to you at the time you left? 14 A. There was a lady by the name of 15 Brenda Roach who was the global project tracking 16 coordinator. 17 Q. Is Ms. Roach still with Lilly? 18 A. Yes. 19 Q. Do you suspect she's still in 20 her same job function? 21 A. Yes. 22 Q. Now as she was when you left in 23 December of 1992? 24 A. Yes. Page 95 1 MR. SMITH: Let's take a break for 2 lunch now. 3 (A LUNCH RECESS WAS TAKEN.) 4 Q. Mister Noone, how many Lilly 5 employees are there in the Indianapolis facility, 6 approximately? 7 A. I don't know, eight to ten, 8 twelve thousand, somewhere in that neighborhood. 9 Q. Ten to twelve thousand? 10 A. Eight to ten to twelve. 11 Q. Has Lilly ever offered to its 12 employees the opportunity to participate in 13 clinical trials with respect to any of its drugs? 14 A. Employees? 15 Q. Yes. 16 A. I don't know. 17 Q. Obviously in a community of 18 eight to ten thousand individuals, you could 19 expect to find individuals suffering from 20 depression within that amount of people; correct? 21 A. I would say that's probably 22 true. 23 Q. And I would assume that the 24 individuals at Lilly, employed by Lilly, suffer Page 96 1 the same psychiatric and psychological and 2 physiological problems that humans everywhere do? 3 MR. MYERS: To the extent that may be a 4 medical question, if he knows as an employee over 5 there, he can tell you, but I don't know that he 6 can tell you from a medical standpoint. 7 Q. You don't have any reason to 8 believe that the employees of Eli Lilly and 9 Company are more or less healthy than the general 10 population, do you? 11 A. I can't really answer that. 12 Q. In other words, the individuals 13 within the Lilly group here should present a 14 percentage of individuals who are indeed 15 clinically depressed? 16 MR. MYERS: Same objection. If you 17 know, tell him. 18 A. I don't know. 19 Q. Have you ever talked to any 20 employees of Lilly who indicated that they had at 21 times suffered from depression? 22 A. No. 23 Q. Have you ever talked to any 24 Lilly employees who have been treated for Page 97 1 depression? 2 A. Probably somewhere in my 3 career, I have, but I certainly can't pinpoint 4 that. 5 Q. I'm not asking for names, 6 specific percentages or anything of that nature, 7 I'm just wondering if Lilly has any program to 8 identify within its employees individuals who are 9 depressed and to help them with treatment of that 10 particular illness. 11 A. I'd logically say that there's 12 probably some employees that are depressed, but 13 other than saying that, I don't know what else I 14 could say. If an employee has a problem, we 15 would try to help them through it. 16 Q. Well, is there some wellness 17 program, ongoing physical or mental health 18 awareness program within the Lilly employee 19 group? 20 A. I don't know of any, I don't 21 know of any formal program that we do have. 22 That's not to say it doesn't exist, I don't know. 23 Q. Do you know of any Lilly 24 employees who have taken Fluoxetine Hydrochloride Page 98 1 for any reason? 2 A. I've heard of some that have, 3 yes. 4 Q. Have you, in your capacity, on 5 any of your job titles, been made aware of a 6 Lilly employee who has had an adverse drug 7 experience from Prozac? 8 A. Not that I am aware of. 9 Q. Do you know if any effort has 10 been made to determine whether or not any Lilly 11 employees have been involved in any of the 12 Fluoxetine Hydrochloride clinical trials? 13 A. Say that question again? 14 Q. Do you know if any effort has 15 been made by anybody within the Lilly 16 organization to determine whether or not any 17 Lilly employees have participated in any of the 18 Fluoxetine Hydrochloride clinical trials? 19 A. I don't know of any effort. 20 Q. At lunch we were confused. The 21 new compound that's being investigated as an 22 antidepressant, did you say it was or was not, 23 according to your recollection, a specific 24 seratonin reuptake inhibitor? Page 99 1 A. I think what I said was I 2 didn't know, but I didn't think that it was. 3 Q. Didn't think it was an SSRI? 4 A. Right. 5 Q. But again, you're not sure 6 about that? 7 A. That's correct. 8 Q. Do you know the number of 9 individuals who currently have been the subject 10 of clinical trials on that particular compound? 11 A. No, I don't know the number. 12 Q. Do you know the number of 13 studies that have been done at this time? 14 A. No. There's not been a whole 15 lot, but I don't know what the number is. 16 Q. Do you know whether or not the 17 investigators have been hired on an outside basis 18 to conduct these clinical studies? 19 A. Yes. 20 Q. And have they been -- when I 21 say outside basis, you have contracted with a 22 particular organization to conduct a clinical 23 trial on this compound that's under 24 investigation? Page 100 1 A. We have contracted individuals 2 who study on this compound, yes. 3 Q. Contracted individuals or 4 companies that do the studies? Do you follow the 5 distinction I'm making? 6 A. Maybe you better clarify it. 7 Q. As I understand it, for 8 instance in the Fluoxetine Hydrochloride 9 depression trials, a physician by the name of 10 Fabre in Houston did some clinical trial work, 11 and he was hired as an investigator for Lilly. 12 Lilly hired him directly, as I understand it. 13 A. Right. 14 Q. However, there are companies, 15 as you probably well know, who Lilly can go to 16 and say we have a particular 17 psychopharmacological drug that we're going to 18 investigate, we would like for you to contract 19 out, secure for us investigators, get for us a 20 plan of, you know, help us in getting this thing 21 done, as opposed to doing it yourself. 22 A. Right. 23 Q. My question is: How are you 24 doing the clinical trials with respect to this Page 101 1 antidepressant compound that's being investigated 2 now? 3 A. I can't speak to all the 4 studies. The studies of which I'm aware, we are 5 working directly with the investigators with our 6 own internal organization. 7 Q. Do you know of any Fluoxetine 8 clinical trials, whether depression or otherwise, 9 that are being done by, let's call it, contract 10 entities who are conducting the clinical trials, 11 as opposed to working directly with the 12 investigator? 13 A. I'm not aware of any. 14 Q. As I understand it, you say 15 you're only aware of two particular ongoing 16 clinical trials with respect to Fluoxetine 17 Hydrochloride? 18 A. That's correct. 19 Q. For any purpose? 20 A. That's correct. 21 Q. Have there been any clinical 22 trials with respect to Fluoxetine Hydrochloride 23 for any purpose that have been completed since 24 December of 1992, in other words that were Page 102 1 underway when you began as project coordinator, 2 but have been completed prior to now? 3 A. I'm not aware of any offhand. 4 That's not to say that there couldn't have been 5 some that finished up during that period of time, 6 but I'm not aware of those. 7 Q. Would you not be made aware of 8 varying schedules as particular trials became 9 completed in your capacity as manager of clinical 10 research coordination? 11 A. Most of them, I would be aware 12 of. But the issue is that the continuum, from 13 the time that I came on to the time where I'm at 14 right now, there could have been some things that 15 had finished up here, and there might have been a 16 few sites that had finished subsequent do that 17 time, and I'm just not aware -- nothing sticks 18 out in my mind about anything that was finished 19 up in that time, between December of '92 and now. 20 Q. How about between January 1, 21 1988 and December, 1992? 22 A. December, '88 to January, '92? 23 Q. No, January, 1988 to December, 24 1992? Page 103 1 A. I'm sure that there were 2 studies done and finished during that time, but 3 I'm not familiar with what they were. 4 Q. Have you ever seen a breakdown 5 of all the clinical studies that were done in 6 connection with Fluoxetine showing information 7 concerning any kind of status with respect to 8 those studies? 9 A. I don't recall seeing anything 10 like that, no. 11 Q. Wouldn't that be something of 12 interest that you would want to know when you 13 began as manager of clinical research 14 coordination? 15 A. No, not really. 16 Q. Why? 17 A. Really more focused on 18 developing compounds. 19 Q. Well, your title doesn't 20 indicate that you're limited to clinical research 21 and development of compounds, does it? 22 A. No, it doesn't state that in 23 the title, no. 24 Q. And your job actually doesn't Page 104 1 limit itself to management of developmental 2 compounds, does it? 3 A. That's correct. 4 Q. You're in charge of all the 5 clinical research -- coordinating all the 6 clinical research throughout the United States of 7 all Lilly products, are you not? 8 A. That's correct. 9 Q. And you know of no other 10 Fluoxetine studies other than those you described 11 to us at this time? 12 A. That's correct. 13 Q. Do you know of any studies 14 where Fluoxetine is being used as the comparitor 15 drug? 16 A. I'm not aware of any. 17 Q. Would there be -- 18 A. That is of Lilly studies. 19 Q. Yes. 20 A. Right, I'm not aware of any. 21 Q. Do you know -- that brings me 22 to the next question, which is a good question, 23 and I appreciate you suggesting it to me. Do you 24 know whether or not any other pharmaceutical firm Page 105 1 is involved in clinical trials where Fluoxetine 2 is being used as a comparitor drug? 3 A. I'm not aware of any. 4 Q. Would there be anyone who would 5 be responsible for having that particular 6 knowledge within the Lilly group? 7 A. Repeat the -- because you're 8 referencing another question, so -- that have 9 particular knowledge of -- 10 Q. Whether or not Fluoxetine is 11 being used by some other pharmaceutical company 12 as a comparitor drug for some other 13 pharmaceutical products either in development or 14 in some study currently? 15 A. There's no formal area that I 16 would know of where that information would be 17 collected. 18 Q. When there's a clinical study 19 that involves a comparitor drug, is there any 20 requirement that the pharmaceutical firm that's 21 conducting the study, that's comparing their 22 product with a comparitor drug, advise or get the 23 approval of the manufacturer of the comparitor 24 pharmaceutical? Page 106 1 A. That's testing my memory. It 2 seems to me there is something in either the IND 3 or NDA regulation that relates to that, but I'm 4 not familiar with it at this point. 5 Q. Do you know of any Lilly policy 6 concerning the use of their products as 7 comparitor drugs in clinical trials of competing 8 pharmaceutical firm products? 9 A. Well, if we're made aware of 10 information that has to do with adverse events on 11 our products, then we would follow the regulation 12 and submit that according to whatever applies. 13 Q. All right. 14 A. But you have to understand that 15 we wouldn't necessarily know about when our drugs 16 are being used as a comparitor. 17 Q. I understand. 18 A. Okay. 19 Q. I would assume that all the 20 investigator -- well, let me back up with that. 21 A. Okay. 22 Q. In a Lilly clinical trial, it's 23 common to compare a Lilly product with a 24 comparitor product -- with a comparitor drug. Page 107 1 A. Sometimes. 2 Q. Which may be a product of some 3 other pharmaceutical firm; correct? 4 A. Sometimes. 5 Q. In those clinical trials where 6 Lilly is comparing their product or Lilly is 7 conducting a clinical trial, and -- let's say on 8 Fluoxetine, and they're comparing it with say 9 Imipramine, all right. As I understand it, if 10 the study is double-blind, the investigator is 11 going to be shipped the research product, that 12 is, say in this instance, Fluoxetine, then 13 they're going to be shipped -- the investigator's 14 going to be shipped the comparitor product or a 15 placebo; correct? 16 A. Uh-huh. 17 MR. MYERS: Say yes. 18 A. Yes. 19 Q. And the investigator -- and 20 that's done from Lilly headquarters or somewhere 21 off site from where the investigation is being 22 done; correct? 23 A. It would be done somewhere, 24 yes. Page 108 1 Q. Obviously Lilly has got to 2 secure the comparitor product to ship to the 3 investigator, don't they? 4 A. It would be important that yes, 5 we could define which was which, yes. 6 Q. I mean if it's a double-blind 7 trial, you're not going to want the investigator 8 to know, but Lilly is going to want to have some 9 record of what particular medication a particular 10 patient is receiving at a particular time? 11 A. That's correct. 12 Q. So Lilly has got to have a 13 supply of the comparitor product to send to the 14 investigator; correct? 15 A. That's correct. 16 Q. But this comparitor product, 17 say Imipramine, is a product that cannot be 18 dispensed without a prescription, so somebody is 19 going to have to have the authority within Lilly 20 to get the prescription for or get the supply of 21 the comparitor product. Are you with me still? 22 A. Yes. 23 Q. How does Lilly do that, how 24 does Lilly secure the comparitor product? Page 109 1 A. I have never been involved with 2 that, I don't know. 3 Q. Who would know? 4 A. I would say somebody in the -- 5 well, again, I'm not sure of the process, but 6 someone in the medical division would know that 7 answer, someone in the cluster may know that, 8 clinical research administrator. 9 Q. Well, do you have some 10 reciprocal agreement with other pharmaceutical 11 firms where you will make a request for the 12 comparitor product for a particular clinical 13 trial from them, and then later on you might 14 reciprocate where they're running a clinical 15 trial and they need one of your products, so you 16 ship them a quantity of your product? 17 A. Not that I'm aware of. 18 Q. You just don't know how 19 comparitor drugs move between -- 20 A. That's correct. 21 Q. -- pharmaceutical firms. 22 A. Right. 23 Q. But you know there's got to be 24 some mechanism whereby that transfer occurs, Page 110 1 don't you? 2 A. Yes. 3 Q. Okay. What arrangements, in 4 your experience as director of medical regulatory 5 affairs -- no, manager of regulatory affairs, 6 head of medical regulatory affairs, department 7 head of medical regulatory affairs, and as 8 manager of clinical research coordination, what 9 is Lilly's policy in connection with ensuring 10 that if their drug is used as a comparitor 11 product, that adverse reactions that are seen in 12 their product as used as a comparitor product, 13 that Lilly is informed of these adverse 14 reactions? 15 A. If we are using our drug as a 16 comparitor, then obviously our procedures cover 17 it. If someone else uses our drug, we have no 18 way of knowing necessarily that they're even 19 using our drug as a comparitor. 20 Q. Well, you would if you had some 21 agreement whereby -- 22 A. Yes, but I don't know that we 23 have an agreement like that. 24 Q. Well, aren't there regulations Page 111 1 that require that a pharmaceutical firm such as 2 Lilly account for prescription medications? 3 MR. MYERS: When you say account for, 4 what do you mean? 5 Q. An accounting. That they 6 produce ten thousand pills in one day, that they 7 be able to tell where the ten thousand pills 8 went; correct? 9 A. We would know where we shipped 10 them to, yes. 11 Q. So if you shipped them to 12 another pharmaceutical firm, there should be some 13 record of that, should there not? 14 A. If we did, yes, I would assume 15 there is. But I don't know anything at all about 16 the distribution channels. 17 Q. But you've been involved in 18 regulations and in observing and collecting 19 adverse reactions with respect to Lilly products, 20 have you not? 21 A. I have been involved, yes, with 22 regulations that affect Lilly products. 23 Q. Which would include 24 compilations of adverse reactions to Lilly's Page 112 1 product, would you not? 2 A. That are reported to us. 3 Q. I understand that you can't use 4 ESP to find adverse reactions, that you have to 5 be made aware of them -- 6 A. Right. 7 Q. -- in some manner. But 8 basically, since 1985, it's my understanding that 9 your function with Lilly has been in ensuring 10 that Lilly complies with various federal 11 regulations with respect to the manufacture and 12 sale of pharmaceuticals, and specifically in 13 collecting, observing and reporting adverse 14 reactions to pharmaceuticals manufactured by 15 Lilly, has it not? 16 A. I think the statement is 17 probably too broad sweeping. Yes, my 18 responsibility was to help to ensure that we 19 abide by the regulations, that's true. 20 Q. What was too broad or too 21 sweeping? 22 A. It sounded like that I had full 23 responsibility for assuring that we were 24 complying with all regulations everyplace, and I Page 113 1 would not attempt to say that that was my 2 responsibility. 3 Q. Somebody has to have ultimate 4 responsibility within a corporation, don't they, 5 Mister Noone? 6 A. Yes. 7 Q. And accountability, don't they? 8 A. Yes. 9 Q. Who has ultimate responsibility 10 and accountability for those areas I just 11 mentioned? 12 A. State the areas again. 13 Q. In ensuring or in attempting to 14 ensure, within the best ability humanly possible, 15 that the company is complying with applicable 16 regulations concerning the manufacture, sale and 17 distribution of pharmaceutical products, who has 18 the ultimate accountability and responsibility 19 for that -- 20 A. Well -- 21 Q. -- within the Lilly group? 22 A. Again, that's -- in dealing 23 with that entire range of what you described, 24 that responsibility is distributed through each Page 114 1 one of the various functional areas. So there's 2 no one person that has that full responsibility 3 that covers the range of all the things that you 4 described there. 5 Q. Is that responsibility within 6 one group of individuals? 7 A. Is the responsibility within 8 one group of individuals? No, not based on all 9 the areas that you covered. 10 Q. What groups of individuals 11 would be included then? I'm talking about 12 ultimate responsibility and accountability. 13 A. For all regulations? 14 Q. Yes. Or regulations with 15 respect to the manufacture, sale and distribution 16 of pharmaceuticals. 17 A. Again, that responsibility is 18 split across manufacturing areas, split across 19 medical areas and regulatory areas. 20 Q. Who has ultimate accountability 21 and responsibility for reporting to the Food and 22 Drug Administration the conduct of Eli Lilly and 23 Company in conducting clinical trials in the 24 United States of America? Page 115 1 A. I'm going to say it's going to 2 vary by product. 3 Q. Central nervous system 4 products? 5 A. It depends on the product, 6 again, specific product. 7 Q. Fluoxetine Hydrochloride? 8 A. The research physician would 9 have responsibility for medical information. 10 Q. Who is that now? 11 A. Well, as I clarified this 12 morning, I'm not sure who has that specific 13 information. It could be John Heiligenstein, but 14 I'm not sure who the specific research physician 15 is at this point. 16 Q. Who was it in December of 1987 17 when Fluoxetine Hydrochloride was approved for 18 sale by Eli Lilly and Company to the public? 19 A. That had been rotated through 20 several people, I'm not sure who had it at that 21 time. 22 Q. What other individuals have had 23 that responsibility since December of 1987? 24 A. I would say a number of Page 116 1 research physicians, Joe Wernicke was one of 2 them. 3 Q. Who else? 4 A. David Wheadon. It seems like 5 Doctor Street did. 6 Q. Jamie Street? 7 A. Yes. It seems like, maybe, 8 Doctor Beasley did. 9 Q. Was he a medical director? 10 A. No. 11 Q. Why would he have ultimate 12 responsibility and accountability in the medical 13 end then? 14 MR. MYERS: I'm going to object to the 15 form, that wasn't the question he's been 16 answering. 17 A. Yes. 18 MR. MYERS: He's been telling you who 19 some of the research physicians for Fluoxetine 20 are. 21 Q. Then we better clarify that, 22 because as I understand it, my question 23 originally was who has ultimate responsibilities 24 for ensuring that Lilly complied with Food and Page 117 1 Drug Administration regulations in connection 2 with the administration of clinical trials in the 3 United States of America? 4 A. That wasn't the question. The 5 question I heard was having to do with 6 manufacturing and distribution, you were cutting 7 across a whole breadth of areas. 8 Q. I thought that you said that's 9 too broad, and I was attempting to limit it to 10 clinical trials. Who has or had ultimate -- 11 let's just start over again. 12 A. Okay. 13 Q. Who has or had ultimate 14 responsibility and accountability for reporting 15 or ensuring that the clinical trials are 16 conducted in accordance with Food and Drug 17 Administration regulations? And those clinical 18 trials I'm speaking of are those clinical trials 19 that are conducted in the United States of 20 America. 21 A. I would say it's the research 22 physician, and then on up through the line that 23 they report to, all those folks would have 24 responsibility. Page 118 1 Q. I'm wanting the ultimate 2 responsibility with respect to clinical trials. 3 A. I'm not sure I can tell you 4 where the buck stops, who is the one that's most 5 responsible. 6 Q. Well, do you know if the Food 7 and Drug Administration has regulations with 8 respect to who they're looking for within the 9 firm or within the company to be accountable for 10 clinical trials? 11 A. It seems to me we have the 12 physician's name that's on documents as things go 13 in, research physician. 14 Q. Who certifies at Lilly that 15 clinical trial data is accurate, is there a 16 requirement from the Food and Drug Administration 17 that clinical trial data be certified by Lilly as 18 being accurate? 19 A. You would have to ask somebody 20 else that question, I have not dealt in that 21 area. 22 Q. That issue hadn't come up since 23 you've been the manager of clinical research 24 coordination? Page 119 1 A. It's not been directed to me if 2 it has. 3 Q. That question did not come up 4 while you were the manager of medical regulatory 5 affairs? 6 A. Not to me. 7 Q. That question didn't come up 8 while you were a department head in medical 9 regulatory services? 10 A. Not to me. 11 Q. What is your understanding, 12 Mister Noone, with respect to when clinical 13 trials first began with respect to Fluoxetine 14 Hydrochloride? 15 MR. MYERS: When in time? 16 MR. SMITH: Yes. 17 A. I couldn't tell you that. 18 Q. We know that approval was given 19 by the Food and Drug Administration in December 20 of 1987 to market the drug; correct? 21 A. That's correct. 22 Q. What is your recollection of 23 when the first clinical trials were done? 24 A. I don't know, it would be in Page 120 1 the IND, though. 2 Q. I understand that, we've been 3 down there, down there with you, down there where 4 the IND is. 5 A. Yes, we did. 6 Q. Nobody had any luck during that 7 occasion of looking for anything, did they? 8 MR. MYERS: I don't recall that I did. 9 It's in the record. 10 MR. SMITH: That's only because you had 11 gone through and marked ninety percent of it out. 12 MR. MYERS: And I flagged what I wanted 13 to look for. It was a set up, I was a shill of 14 some type. 15 THE WITNESS: He was trainable. 16 MS. ZETTLER: You mean Larry was 17 trainable? 18 Q. Can you give me anybody during 19 any of the clinical trial phase that had ultimate 20 responsibility for accurately reporting to the 21 Food and Drug Administration the results of the 22 clinical trials done on Fluoxetine Hydrochloride 23 for treatment of individuals suffering from 24 depression? Page 121 1 A. Can I give you anyone who had 2 responsibility for the medical side of it? 3 Q. Yes, ultimate responsibility 4 for accurately reporting to the Food and Drug 5 Administration the results of clinical trials? 6 A. I would say that would be a 7 research physician. 8 Q. The particular research 9 physician involved in a particular study? 10 A. For the data that's in that 11 study? 12 Q. Yes. 13 A. Yes, the research physician 14 would have responsibility for that. 15 Q. In other words, there was more 16 than one research physician involved throughout 17 Fluoxetine's clinical trial? 18 A. That's correct. 19 Q. And at the same time, there may 20 have been more than one clinical -- there may 21 have been more than one research physician 22 working on clinical trials? 23 A. That's true. 24 Q. But there wasn't a research Page 122 1 physician that was -- that had the ultimate 2 responsibility, was there, to ensure that the 3 clinical trial data was accurately reported to 4 the Food and Drug Administration? 5 A. Repeat the question again. 6 (THE COURT REPORTER READ BACK THE 7 REQUESTED TESTIMONY.) 8 A. There would have been somebody 9 on a given submission that would have had 10 responsibility when it was submitted to the FDA. 11 Q. Is there -- since you've been 12 involved in regulations and regulatory affairs 13 since 1985, is there some certifying document 14 where the research physician signs some pledge or 15 some -- makes some type of certification to the 16 Food and Drug Administration by his signature 17 that the data submitted is accurate with respect 18 to what occurred during a clinical trial? 19 A. There are numbers of documents 20 around that people sign off on, but I don't know -- 21 I'm not familiar with the specific document that -- 22 to which you might be speaking. 23 Q. Well, the new drug application 24 itself is a document that begins with the Page 123 1 application itself -- 2 A. You're talking about the form? 3 Q. Yes. 4 A. Yes. 5 Q. That has the signature on it 6 that certifies that the information that is 7 submitted is true and correct, does it not? 8 A. I don't remember the wording, I 9 know there is such a form, it goes on top of the 10 NDA submission, and as I recollect there is 11 someplace where someone signs, but I couldn't 12 tell you what the words are that are on that 13 form. 14 Q. Your impression is is that it 15 is a signature attesting that the information 16 that's being submitted is true and correct? 17 A. I would have to go back and 18 look at the form. 19 Q. You don't have any impression 20 of what that form says? 21 A. I don't remember what the form 22 says. 23 Q. I know you don't remember what 24 the form says because you told me you don't Page 124 1 remember. My question is: What is your 2 impression of what the form says? 3 A. I don't know that that is 4 relevant, I guess that's the only way I can 5 answer that. If I don't know what the form says, 6 then I don't know what good it does to provide my 7 impression of what's on the form. 8 Q. Well, you've seen the form, 9 have you not? 10 A. I have seen it, yes, in years 11 past. 12 Q. Have you ever signed an NDA? 13 A. No. 14 Q. Who usually signs the NDA? 15 A. Seems like things like that are 16 signed off on -- perhaps by the director of 17 medical regulatory affairs. 18 Q. That would be Mister Talbott 19 currently, Doctor Talbott? 20 A. Right. 21 Q. But you don't recall what it 22 says there where he signs it in connection with 23 what he's attesting to? 24 A. No. Page 125 1 Q. All right. I want to go back 2 with you if I can, Mister Noone, and talk with 3 you concerning your days as manager of medical 4 regulatory affairs and as department head of 5 medical regulatory affairs, okay. That would be 6 inclusive of the years 1985 through 1982, would 7 it not? 8 A. Department head, yes, in 1985, 9 and then manager in 1988. 10 Q. And during that period of time, 11 you were involved, at least in part -- part of 12 your duties involved the collection and reporting 13 of adverse events that occurred during clinical 14 trials with respect to Fluoxetine, and adverse 15 events or spontaneous reports or reports of any 16 nature to Lilly that occurred post-marketing? 17 A. Part of that time was devoted 18 to the collection of information related to 19 adverse events, that's true. 20 Q. What part of that time was 21 related to that? 22 A. In '88, I assumed 23 responsibility for the collection group, which is 24 the drug epidemiology unit, and I had that up Page 126 1 until sometime in '90 or '91. 2 Q. So you were in charge of the 3 DEU from 1988 until 1990-91? 4 A. That's correct. 5 Q. You were the big dog in DEU? 6 A. That was not my title. 7 Q. But you were the top cat, the 8 big cheese, the big dog, numero uno? 9 MR. MYERS: Tell him what your title 10 was. 11 A. The title was manager of 12 medical regulatory affairs. 13 Q. You were responsible for the 14 day-to-day operation of the entire -- 15 A. Day-to-day administrative 16 operation, right. 17 Q. I understand you were not a 18 clinical research physician that was analyzing 19 some of these reports, you're not a clinical 20 research administrator that was involved in 21 checking out some of these reports, you were not 22 a pharmacist following up on these reports, but 23 you were the administrative person that was 24 heading up the entire group; correct? Page 127 1 A. Right, the drug epidemiology 2 unit. 3 Q. What did you start doing after 4 you left the DEU? 5 A. What did I start doing after 6 the DEU? 7 Q. Yes. Apparently you didn't 8 leave medical regulatory affairs until December 9 of 1992. 10 A. Okay. No, I had several groups 11 that reported to me, even at the time the drug 12 epidemiology unit -- at the time I had it. 13 Subsequent to the drug epidemiology unit and 14 moving off to another group, I picked up another 15 group, so we just swapped areas, parts of areas. 16 Q. What did you pick up? 17 A. Medical writing services. 18 Q. At the time you began medical 19 writing services, did that mean that you did not 20 administer on a daily basis the drug epidemiology 21 unit? 22 A. That's correct. 23 Q. And your duties at the drug 24 epidemiology unit with respect to administering Page 128 1 that unit ceased? 2 A. Right, that's correct. 3 Q. Who took over for you in that 4 position? 5 A. That was passed on to Earlene 6 Ashbrook as the manager. 7 Q. She had been your number one 8 assistant? 9 A. No, she had -- she reported to 10 Doctor Talbott, I reported to Doctor Talbott, we 11 just switched parts of our areas at that point. 12 Q. Okay. 13 A. So she still had parts of her 14 other areas. 15 Q. So at the time you were the 16 chief administrator in the DEU, what other job 17 functions did you have in addition to the drug 18 epidemiology unit? 19 A. I had the international product 20 registration department, I had the reprints area. 21 Q. What is that? 22 A. An area that would seek to get 23 author and publisher approval for scientific 24 articles that appeared in journals. Page 129 1 Q. You sought to get author and 2 publisher approval? 3 A. Right. 4 Q. Okay. So you would submit a 5 particular publication to a particular journal 6 and try to get it published? 7 A. That's one thing. This is 8 really the tail-end process. This is -- it's 9 published, therefore regardless of who had it 10 published, we would seek author and publisher 11 approval in order to purchase certain numbers of 12 that article. 13 Q. Like a redistribution? 14 A. Yes, it could be used for our 15 sales representatives in detailing if it was 16 within labeling. It could also just be used for 17 in-house distribution so that people would know 18 what was being written about the drugs. 19 Q. What else? 20 A. Medical editorial services. 21 Q. What is that? 22 A. Essentially the group that 23 coordinates from an administrative standpoint the 24 package literature labels on the product. Page 130 1 Q. Okay. Like the package insert? 2 A. Yes. 3 Q. All right. What other duties? 4 A. The global project tracking 5 drug experience network coordinators reported to 6 me also. 7 MS. ZETTLER: What was that, I'm sorry? 8 THE WITNESS: Global project tracking 9 system and drug experience network coordinators. 10 Q. What else? 11 A. Regulatory services. 12 Q. What is that? 13 A. That's basically the 14 record-keeping function that tracks the -- or 15 keeps copies of what we submit to the U.S. Food 16 and Drug Administration, whether it's IND or NDA 17 or other. 18 Q. What other duties did you have 19 during that period of time? 20 A. At the time that I had the drug 21 epidemiology unit, that was it. 22 Q. How much percentage of your 23 time did you spend in administering the drug 24 epidemiology unit during that time versus these Page 131 1 other functions that you described, international 2 product regulation, reprints area, medical 3 editorial services, global project tracing, DEN 4 coordinator, administrator, and regulatory 5 services? 6 A. It would be difficult to say, 7 except for -- because there were different -- at 8 different points in time there was a high 9 proportion of time that was spent with the drug 10 epidemiology unit, especially whenever we 11 reorganized. Other times I would spend more time 12 with other areas. And it would depend on the 13 number of staff that I had and how well trained 14 they were. 15 Q. When did you reorganize the 16 drug epidemiology unit? Am I getting better at 17 saying that? 18 MR. MYERS: Yes, epidemiology is much 19 better. You're a most improved student on that. 20 A. Repeat the question again. How 21 many times? 22 Q. No. You said that the drug 23 epidemiology unit was reorganized? 24 A. Yes. Page 132 1 Q. My question was when and why? 2 A. A couple of different times, 3 one when the work volume increased and we had new 4 people, we reorganized. 5 Q. When was that? 6 A. Oh, boy, I would have to guess 7 somewhere maybe late -- maybe late '89 or early 8 '90, somewhere in that neighborhood. 9 Q. And this was with respect to 10 the increased number of adverse reactions that 11 were being reported on -- 12 A. That's correct. 13 Q. -- Fluoxetine, Prozac? 14 A. Primarily Fluoxetine, but we 15 had other compounds that were new at that time as 16 well. 17 Q. But Prozac was leading the 18 list? 19 A. Right. 20 Q. By what, five to one margin? 21 A. I don't know what the number 22 would have been. 23 Q. We'll go over those in a 24 minute. What's your recollection of the Page 133 1 percentage of adverse reactions Lilly was getting 2 on Prozac versus its other products? 3 MR. MYERS: You mean adverse experience 4 reports? 5 MR. SMITH: Uh-huh. 6 A. That would be hard to say, 7 Paul. It would depend on the point in time, 8 because it did, obviously, change, as you can 9 well imagine. When the drug was introduced, you 10 would have very small numbers, and as it's 11 increased, then the number -- the use increases, 12 the numbers increase. If you have a media event, 13 you also get increased numbers. 14 Q. Well, Prozac was featured in a 15 cover article on Newsweek magazine, was it not? 16 A. That's correct. 17 Q. Did you find an increased 18 number of reports to Lilly of adverse events 19 experienced with Prozac following that Newsweek 20 cover article? 21 A. I can't specifically cite what 22 the impact was on that particular article. I 23 don't know what the numbers were at that time. 24 Q. You indicated that you Page 134 1 reorganized once in late 1989 or early 1990, 2 handling increased work load within the drug 3 epidemiology unit by virtue of the increased 4 sales and/or publicity with respect to Prozac. 5 A. Right. 6 Q. Then I took it from your answer 7 that there was another time where reorganization 8 occurred? 9 A. Yes, as we went to further 10 enhance our systems applications. 11 Q. When was that? 12 A. Well, it was sometime after 13 that, but I couldn't tell you what the exact time 14 was. 15 Q. What was done to enhance your 16 systems applications? 17 A. We moved to having adverse 18 events -- we went to having on-line capability 19 from the affiliates, in which case -- many of the 20 affiliates, in which case they no longer needed 21 to call or fax information, they could now 22 provide it to us alive, on line. 23 Q. When you say affiliates, are 24 you talking about Lilly division subsidiaries in Page 135 1 foreign countries? 2 A. Yes, international foreign 3 country affiliates, yes. 4 Q. And at some point, instead of 5 calling in these adverse experiences or faxing 6 these in, they had their computer that would link 7 up to your computer? 8 A. That's correct. 9 Q. And they could make a computer 10 entry there in Britain that would automatically 11 show up in Indianapolis, Indiana? 12 A. That's correct, right. 13 Q. When did that get on line? 14 A. Sometime, I think it was in 15 '89, but I don't remember the date. 16 Q. All right. 17 A. Because it was phased as well. 18 Q. And that gave you the capacity 19 to instantaneously monitor adverse events that 20 occurred across the ocean in England? 21 A. I'm not sure I understand the 22 term monitor. What I stated before was that we 23 could now have it automatically entered into the 24 system, so it wasn't necessary for somebody to Page 136 1 fax and somebody in turn to enter it on our end. 2 Q. The computer entry only had to 3 be done once? 4 A. That's correct. 5 MR. SMITH: Let's take a quick break. 6 MR. MYERS: Sure. 7 (A SHORT RECESS WAS TAKEN.) 8 (PLAINTIFFS' EXHIBIT NO. 1 WAS 9 MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. Mister Noone, let me hand you a 12 document marked as Exhibit 1 in connection with 13 this realignment and reorganization that 14 occurred, and I give you this document and make a 15 representation to you that this was a document 16 that was submitted to us that supposedly came 17 from a file of yours which probably you turned 18 over to legal. In any event, this may refresh 19 your recollection concerning when this particular 20 reorganization occurred. If you need some time 21 to read the document -- 22 A. Yes, please. 23 Q. -- we will sure give you that 24 time. Page 137 1 MR. MYERS: Is the question does it 2 refresh him as to when the reorganization took 3 place? 4 MR. SMITH: That would be an 5 appropriate question. 6 A. Was there a reorganization at 7 this time? 8 Q. Yes. 9 A. Yes. 10 Q. For identification, Exhibit 1 11 is, looks like a memo authored by you. 12 A. That's correct. 13 Q. On the second page of that 14 document, it says Noone, Michael S., and then 15 there is a notation out by this, looks like, IVM, 16 either I or one. Can you tell me what those 17 particular initials designate? 18 A. That's just what shows up when 19 I send something on electronic mail. 20 Q. Does it designate a title, a 21 position? 22 A. Nothing I'm aware of, it's just 23 always been there. Whenever I send a message, it 24 always has my name like that, and this has this Page 138 1 notation out here to the side. It automatically 2 comes up. 3 Q. It's sort of like a tattoo or 4 something, isn't it, you see it on all the memos? 5 A. Right. It's nothing I key in. 6 Q. It's always been the same? 7 A. I haven't really paid that 8 close attention to it, I always know there's 9 something that's out there, but what happens, 10 what I key in is stopped after -- you see the 11 word Mike, and then I send it, and when it shows 12 up -- when it's at somebody else's desk or if I 13 copy myself on it, then that's what comes up on 14 the bottom. 15 Q. The thing is, though, IVM1 16 appears by a lot of people's names. Have you 17 noticed that a lot of people have got the IVM1 18 designation by their name? 19 A. Yes. I guess I have seen 20 something out there, but I've never paid much 21 attention to it. 22 Q. Do you read much E-Mail? 23 A. Yes. 24 Q. Daily? Page 139 1 A. Yes. 2 Q. And you see this IVMI by a lot 3 of names on a daily basis. 4 A. It's probably not something 5 that I pay a whole lot of attention to because my 6 focus is going to be not down at the bottom. 7 Q. I understand. But even when 8 you see CCs on a document, a lot of times, you 9 see a long document and you'll see a bunch of 10 IVMIs, and stuff like that, won't you? 11 A. Are they all IVM1? 12 Q. Uh-huh. We don't even need to 13 mark these, I mean this is -- we just see it 14 everywhere. 15 A. Right. 16 Q. Could this be the designation 17 for somebody in the medical division maybe? 18 A. I doubt it. 19 Q. You don't have any explanation 20 since -- how long have you been working for 21 Lilly? 22 A. Thirty years. 23 Q. Thirty years. You never were 24 curious as to what those letters meant? Page 140 1 A. Not really, no, it just always 2 showed up up there when we sent messages, so it 3 wasn't something I keyed in, so I assumed it was 4 just probably something that related to the 5 computer system. 6 Q. All right, back to Exhibit 1. 7 This has to do with realignment of 8 responsibilities in the DEU, which is the drug 9 epidemiology unit, is it not? 10 A. That's correct. 11 Q. And it appears that Monday, 12 November 17, 1989 is the date that this 13 reorganization is effective. 14 A. That's correct. 15 Q. And is that the date in late 16 1989 that you were talking about when the work 17 load increased because of the increased volume of 18 adverse drug experiences with Fluoxetine? 19 A. As I recall, this was either 20 the second or third reorganization that we had 21 gone through. 22 Q. All right. 23 A. This, as you may recall in the 24 earlier conversations, this is one where I Page 141 1 related that we had -- were dealing with the 2 hotline calls and all that stuff. 3 Q. I don't remember any mention of 4 a hotline, I remember that there was -- you 5 mentioned there was one reorganization when the 6 work load increased due to increased frequency of 7 adverse drug experience. 8 A. Right. 9 Q. Then another reorganization 10 when there was a systems applications where there 11 was on-line capability from the foreign 12 affiliates. 13 A. Right. 14 Q. And that was in 1989. 15 A. Right. 16 Q. Now are you telling me there 17 was a third reorganization in connection with 18 establishment of some type of hotline? 19 A. The -- as you read this here, 20 what we were doing is handling initial hotline 21 calls with this group that we had here. 22 Q. All right. What was the 23 hotline? 24 A. As calls came in, we would have Page 142 1 information that was keyed in immediately from -- 2 if a call came in from, let's say, a sales 3 representative, the information would be keyed in 4 immediately by the person who took the call. And 5 it was a more rapid way for us to process the 6 reports, and it was labor-saving, so we didn't 7 have to have -- we were able to process more 8 reports per day or per week or per month with 9 that accounting we had. 10 Q. Was there published some 11 hotline number for Lilly people or medical 12 practitioners or the public in general where they 13 could dial up a particular number and get the 14 Lilly hotline to report an adverse experience 15 with Prozac? 16 A. There was a hotline number that 17 was provided to Lilly employees, specifically 18 sales representatives, and obviously the Lilly 19 operator was aware of that number as well if 20 calls came in to her or him. 21 Q. When you say sales 22 representive, are you talking about detail 23 people? 24 A. That's correct. Page 143 1 Q. That went to -- that spent 2 their day going to physicians, to discuss Lilly 3 products with physicians? 4 A. Right. 5 Q. Psychiatrists, correct? 6 A. Anyone that they might be 7 detailing. 8 Q. General practitioners. 9 A. Right. 10 Q. Was there some memo that went 11 out to these sales representative drug detail 12 people that said there's a new hotline number 13 that you can call to report an adverse event with 14 Prozac? 15 A. I don't know. The number 16 actually didn't change, it was just the process 17 within the unit changed, in terms of how we 18 handled those calls. The calls would come in 19 just as they did before, but rather than someone 20 spending all their time writing it up, they could 21 just key the information into the system. 22 Q. You say the number didn't 23 change, but was it a number that was answered 24 directly in the drug epidemiology unit? Page 144 1 A. Right. 2 Q. And it was a one eight hundred 3 number? 4 A. I don't remember that it was a 5 one eight hundred number, I think it was some 6 other number. It wasn't an eight hundred, but it 7 was a number that Lilly people had, field sales 8 representatives had. 9 Q. Only Lilly people had. 10 A. Well, Lilly people had that 11 number. There were other numbers that were 12 provided, I do not remember whether those were 13 the same ones at this point to investigators, 14 they were obviously provided with numbers as 15 well. 16 Q. Was it a different number than 17 the hotline number? 18 A. I don't remember now. 19 Q. In any event, this hotline 20 number was a specific number that a Lilly or 21 DISTA sales representative or detail person could 22 dial in, the phone would ring in Indianapolis, 23 Indiana, and it would be answered by someone in 24 the drug epidemiology unit? Page 145 1 A. Right. 2 Q. And that number was reserved 3 for Lilly employees to report adverse reactions 4 to Lilly products to the drug epidemiology unit? 5 A. That's where the focus was, but 6 other people could call in there, too. 7 Q. To report adverse reactions? 8 A. Right. 9 Q. The drug epidemiology unit only 10 dealt with adverse reactions to drugs, didn't it? 11 A. That's correct. Adverse 12 events, you need to carify that. 13 MR. MYERS: You're jumping around with 14 your terminology, and one is broader than the 15 other, really. 16 MR. SMITH: All right. 17 MR. MYERS: I'm not suggesting that 18 it's intentional. I'm not suggesting anything. 19 MR. SMITH: Are you suggesting it's 20 inconsistent? 21 (DISCUSSION OFF THE RECORD.) 22 Q. Was this hotline established 23 because of increased frequency in reports of 24 adverse experiences in connection with Prozac? Page 146 1 A. Prozac would have been one of 2 the primary influencers of that, but other 3 products did contribute to it at that time as 4 well, although I saw on here when this snapshot 5 was taken, Prozac did represent more than half. 6 Q. Yes. 7 A. But there are products that 8 helped influence those numbers. 9 Q. In October of 1989, the number 10 of adverse or the percentage of adverse reports 11 reporting adverse experiences with Prozac was 12 fifty-three percent of all reports of all drugs, 13 was it not? 14 A. That's correct. 15 Q. And that number increased after 16 that, did it not? 17 A. I can't answer that totally. 18 Q. This fifty-three percent of 19 calls in connection with adverse experiences with 20 Prozac was in October, 1989, wasn't it? 21 A. Uh-huh. 22 Q. And that was -- that means that 23 over half of all reports of adverse experiences 24 with Lilly drugs were reported in connection with Page 147 1 the drug Prozac; correct? 2 A. Say it again because there's 3 some tricky wording in there. 4 Q. Over half of all reports that 5 the drug epidemiology unit was getting in October 6 of 1989 had to do with adverse experiences 7 reported with Prozac? 8 A. That's correct. 9 Q. And at that time, in October, 10 1989, the drug epidemiology unit was monitoring 11 adverse experiences with all of Lilly products, 12 weren't they? 13 A. That's correct. 14 Q. How many products did Lilly 15 have on the market in October, 1989? 16 A. Lots, I couldn't tell you the 17 number. 18 Q. Fifty? 19 A. Probably more than that. 20 Q. A hundred? 21 A. Somewhere in that ballpark. 22 Q. Of the one hundred different 23 products that Lilly was marketing in the United 24 States in October of 1989, over half of all your Page 148 1 reports of adverse experiences with Lilly 2 products had to do with Prozac, didn't it? 3 A. That's correct. 4 Q. And after October, 1989, that 5 percentage even went up, didn't it? 6 A. I don't remember whether it did 7 or it did not. 8 Q. Well, I think we've got 9 something that will help you with that. 10 A. Okay. 11 Q. Well, the number of reports 12 went up after the Teicher article came out, 13 didn't it? 14 A. I don't know whether they did 15 or not but I -- 16 Q. You don't know that? 17 A. I don't know that for sure, no. 18 Q. It would be safe to assume, 19 would it not, Mister Noone, that the number of 20 reports having to do with adverse experiences 21 with Prozac went up beyond fifty-three percent 22 after October, 1989, wouldn't it? 23 A. I don't know that it would be 24 safe to assume, I would say that could be an Page 149 1 assumption. 2 Q. It would be a reasonable 3 assumption, too, wouldn't it? 4 A. Not necessarily. 5 Q. Any other reorganizations other 6 than these three that you've told me about? 7 A. I can't recall any others at 8 this time. 9 Q. Now, I need, if I can, to get a 10 picture of the drug epidemiology unit from 1988 11 through 1990 and 1991, when you left. You had, 12 you, yourself, who was administrator, had the 13 ultimate responsibility for administering the 14 unit; correct? 15 A. Right. 16 Q. You had some physicians that 17 were working full-time in the drug epidemiology 18 unit also, did you not? 19 A. No. 20 Q. Did you have some physicians 21 that were -- that you were consulting with? 22 A. Define consulting. 23 Q. Well, that you were having help 24 those individuals within the DEU unit in Page 150 1 responding to calls or reports of adverse 2 reactions to Prozac? 3 A. Well, it's true, it's a shared 4 responsibility between the drug epidemiology unit 5 and the research physicians in assessing the 6 reports. 7 Q. Well, I thought, for instance, 8 Doctor Kotsanos -- do you know Doctor Kotsanos? 9 A. Sure do. 10 Q. Wasn't he a member of the drug 11 epidemiology unit? 12 A. No. 13 Q. What was his function 14 throughout? 15 A. Throughout what? 16 Q. Throughout your -- his 17 association. He was associated with the DEU in 18 some way, was he not? 19 A. Yes, as I recall, maybe as -- I 20 think as a research physician at one time. 21 Q. What did he do for the drug 22 epidemiology unit? 23 A. I think he had product 24 responsibilities for one of the products. Page 151 1 Q. Which product? 2 A. I don't recall, might have been 3 Ceclor. I don't recall for sure. 4 Q. Didn't he work on Prozac? 5 A. I'm not sure that he did, he 6 might have. 7 Q. Well, all right, maybe I got 8 off the track. You've got the drug epidemiology 9 unit, you've got you as chief administrator, all 10 right? 11 A. Manager of the area, yes. 12 Q. Well, as manager of the area, 13 you were the chief administrator, weren't you? 14 A. It depends on how you define 15 chief administrator, I guess, what 16 responsibilities and roles you want to assign to 17 that. 18 Q. Well, I keep trying to give you 19 the role as the responsible person for 20 administering drug epidemiology unit during the 21 time that you were there. Is that incorrect? 22 A. I think it's important to note 23 that a lot of what we do is through concensus and 24 discussion with people, and seldom do people make Page 152 1 a complete one-off decision. 2 Q. How does that have to do with 3 your responsibility in the drug epidemiology 4 unit, Mister Noone? 5 A. I was responsible for 6 administering to the staff that we have there. 7 But in terms of the output, it was a 8 collaborative role between the drug epidemiology 9 unit and the research physicians. 10 Q. Well, but somebody has got to 11 be in charge of something at some time, 12 somewhere, don't they? 13 A. It depends on what it is that 14 you're defining. 15 Q. I'm talking about the drug 16 epidemiology unit. 17 A. Okay. 18 Q. Weren't you in charge of the 19 drug epidemiology unit from 1988 until 1990 or 20 '91, whenever you left? 21 A. I had responsibility as manager 22 of that group, yes. We have a director of that 23 area as well, obviously. 24 Q. All right. But you, as Page 153 1 manager, were over the director, were you not? 2 A. No, I was under the director. 3 Q. The director was Doctor 4 Talbott? 5 A. Right. 6 Q. But he delegated to you the 7 operation of the drug epidemiology unit, did he 8 not? 9 A. Yes. 10 Q. And he held you responsible for 11 what went on in the drug epidemiology unit, 12 didn't he? 13 A. Just as I would hold other 14 people that worked in the unit responsible for 15 what they were doing. 16 Q. Somebody has to have the 17 responsibility to see that people are doing what 18 they're instructed to do, aren't they? 19 A. That's true. 20 Q. And that was you with respect 21 to DEU, wasn't it? 22 A. Right. 23 Q. There may have been issues that 24 required medical judgment in connection with a Page 154 1 particular cause and with respect to particular 2 drugs that might have come through the DEU, and 3 you weren't responsible for that, were you? 4 A. That's correct. 5 Q. You're not a medical doctor. 6 A. Right. 7 Q. But I'm talking about the 8 operation administratively of the unit. Are we 9 together now? 10 A. Yes. 11 Q. Where were you housed, what 12 floor, what wing, what building? Were you housed 13 together, I guess, may be the better first 14 question? 15 A. Let's see if I can remember the 16 time. I was on eleven three, which was next to 17 eight three, for part of that time. 18 Q. What is eleven three? 19 A. It's a building that butts up 20 against eight three. 21 Q. Okay. 22 A. So there was a corridor where I 23 was and where the rest of that unit was. 24 Q. Why were you in a different Page 155 1 building than the rest of the unit? 2 A. Not enough space. 3 Q. Was where you were sort of 4 management space, and where they were sort of 5 staff space? 6 A. No, because I was surrounded by 7 staff on the other -- on the eleven three floor. 8 So I wouldn't call it management space, I was the 9 only manager that was there at the time. And 10 there were associates there, and I think there 11 was a department head there at one time, too. 12 Q. How many total individuals -- 13 or what was the maximum number of people that 14 were members of the drug epidemiology unit during 15 the time you were the head of that unit? 16 A. I would guess approximately 17 eighteen -- I'm going to say maybe twenty. 18 Q. There's eight members of the 19 unit listed in Exhibit 1, is there not? 20 A. No, there's more than that. 21 There's one, two, three, four, five, six, seven, 22 eight, nine, ten, eleven, twelve -- there's 23 twelve on this page, and there's five on the 24 following page, and it's showing one opening. So Page 156 1 that's eighteen. 2 Q. Eighteen. And those eighteen 3 individuals were responsible for collecting all 4 reports of adverse events in connection with 5 Lilly products during that time? 6 A. No, not all. 7 Q. Who else was responsible for 8 collecting? 9 A. They were collecting the 10 spontaneous reports. 11 Q. What's the spontaneous report? 12 A. It's a report that occurs 13 outside of a study, plus certain trial reports. 14 Q. Okay. So during the time that 15 you were head of the drug epidemiology unit, the 16 only adverse reactions that were collected by 17 that unit were adverse reactions reported that 18 were considered spontaneous reports of adverse 19 reactions, and certain trial reports, I assume 20 that's clinical trial reports? 21 A. That's correct. I would say 22 the term is not reaction, again, it's events. 23 Q. Adverse events? 24 A. Right. Page 157 1 Q. Now, that doesn't -- now what 2 is a spontaneous report? 3 A. It's an adverse experience, 4 adverse event that occurs not in a study. 5 Q. So are all reports of adverse 6 events that don't occur during a study called a 7 spontaneous report? 8 A. Yes. 9 Q. Regardless of whether or not 10 that report is serious or expected? 11 A. That's correct. 12 Q. So the DEU is going to collect 13 all spontaneous reports; correct? 14 A. Correct. 15 Q. And do I understand it that 16 they're going to get some certain reports of 17 adverse events that occur during certain trials? 18 A. That's correct. 19 Q. Which ones? 20 A. Which ones -- which trials or 21 which reports? 22 Q. Certain trial reports are 23 included in the DEU's responsibility. 24 A. Those that are defined by the Page 158 1 FDA to encompass the term serious. 2 Q. Is that it? 3 A. That's what they collect, 4 right. 5 Q. All right. So I can get an 6 understanding, I'm not trying to be repetitive 7 with you. 8 A. Okay. 9 Q. But I'm trying to get a 10 definition or a parameter of what the drug 11 epidemiology unit is collecting during the period 12 of time that you were head of that unit. 13 A. All right. 14 Q. And as I understand it, that 15 drug epidemiology unit was collecting, during 16 that period of time, all spontaneous reports 17 concerning adverse events in connection with all 18 Lilly drugs, including Fluoxetine, that occurred 19 outside of a clinical study, all right? 20 A. Correct. 21 Q. Plus they collected certain 22 trial reports of adverse events which were 23 described as serious as defined by the Food and 24 Drug Administration; is that correct? Page 159 1 A. Correct. 2 Q. Did that criteria for inclusion 3 as a report that would be taken remain the same 4 throughout the time that you were administrator 5 of the unit? 6 A. Repeat the question again. 7 Q. Did that criteria or did that 8 classification of reports that would be assembled 9 or collected in the drug epidemiology unit remain 10 the same throughout that period of time? 11 A. Yes, as far as I can recall, it 12 did. 13 Q. Of the spontaneous reports that 14 were collected by the drug epidemiology unit, 15 what percentage of those reports were reported by 16 Lilly employees versus non-Lilly employee 17 physicians -- or directly, said another way, 18 reported by employees of Lilly versus direct 19 independent calls from a physician who had 20 prescribed the medicine? 21 A. I don't have the specific 22 statistics on that, I would say it was a high 23 percentage of those were reported by or through 24 Lilly employees. Page 160 1 Q. Did you ever do anything to 2 make any determination with respect to why there 3 would be such a high percentage of reports from 4 Lilly employees versus physicians? 5 A. I'm sure the sales 6 representatives are in talking to physicians 7 every day, and they were trained that if a 8 physician told them about an adverse event, they 9 had to report it to the drug epidemiology unit 10 within twenty-four hours. 11 Q. All right. Was that a Food and 12 Drug regulation? 13 A. No. 14 Q. It was a Lilly requirement? 15 A. Right. 16 Q. Why was Lilly requiring that -- 17 let me ask it this way: Was Lilly requiring that 18 their sales representives or detail people 19 specifically ask each physician that they called 20 on, have you had any adverse experience with any 21 Lilly products since the last time I saw you? 22 A. That would normally not be what 23 they would be doing, no. 24 Q. In other words, was there a Page 161 1 directive to the sales representatives to make 2 specific inquiry concerning adverse reactions to 3 the drugs? 4 A. Not that I recall, no. 5 Q. So they would be reported by 6 the Lilly representatives if the doctor happened 7 to tell them about it; correct? 8 A. That's correct. 9 Q. But if the doctor didn't 10 mention it, the Lilly employees weren't 11 necessarily going to make inquiry of the doctor 12 concerning whether or not the doctor had 13 experienced a particular adverse reaction for a 14 particular period of time? 15 MR. MYERS: The doctor or a patient of 16 the doctor? 17 Q. Well, you know what I'm talking 18 about, don't you, Mister Noone, whether or not 19 the doctor had reported his patients experiencing 20 these reactions? 21 A. Could you restate the question 22 again? 23 (THE COURT REPORTER READ BACK THE 24 REQUESTED TESTIMONY.) Page 162 1 A. That's correct. 2 Q. During the period of time that 3 you were in charge of the drug epidemiology unit, 4 was there any other system in place by Lilly to 5 monitor adverse experiences with drugs, was there 6 some other collecting pool, agency or data base 7 that was in existence during this time that would 8 have other or the same record of adverse 9 experiences? 10 A. The clinical trial data base 11 would have other events that would have been 12 reported that came in on case report forms that 13 did not meet the criteria that we had set up for 14 the drug epidemiology unit and Drug Experience 15 Network. 16 Q. All right. You just used some 17 terms that we probably need to straighten out, 18 too. You talk about the drug epidemiology unit. 19 A. Right. 20 Q. Which is a division within the 21 medical division at Lilly research laboratories; 22 correct? 23 A. Right. 24 Q. Which is a group of people Page 163 1 performing a particular function, is it not? 2 A. Correct. 3 Q. You also mentioned a drug 4 experience network or DEN. 5 A. Right. 6 Q. Tell us what that is? 7 A. That's the place where the 8 information was put into the system, the adverse 9 events data was put into. 10 Q. Now was the data that was put 11 in the DEN or Drug Experience Network only data 12 from the drug epidemiology unit? 13 A. The data that went into DEN 14 passed through the drug epidemiology unit, 15 correct. 16 Q. Okay. So DEN, the Drug 17 Experience Network data base contained additional 18 data other than that data that was obtained 19 initially through the drug epidemiology unit? 20 A. No, I didn't -- I'm not sure 21 where that came from. My statement was what was 22 put into DEN passed through the drug epidemiology 23 unit and was inputted into DEN. 24 Q. I want to make sure that there Page 164 1 wasn't any other unit, agency or reporting entity 2 that was putting information into the DEN data 3 base. 4 MR. MYERS: Other than the DEU? 5 MR. SMITH: Yes. 6 A. Other than the DEU, that's 7 correct. 8 Q. The DEU is the only group that 9 can get data into the DEN, which is the Drug 10 Experience Network? 11 A. That's not completely true, 12 they would monitor that information that came in 13 to DEN. As you may recall earlier, I said people 14 overseas sent information into DEN. That 15 information was reviewed by the drug epidemiology 16 unit. So they weren't just putting in the 17 information on calls, we had another mechanism by 18 which things did come in to DEN. 19 Q. That's what I want to clarify, 20 is how stuff got to the drug epidemiology unit 21 and how stuff got into DEN. Then you mentioned 22 the clinical trial data base, and we'll talk 23 about that in a minute. I'm just trying to get 24 from you definitions and parameters with respect Page 165 1 to these various entities that we've got, okay? 2 A. All right. 3 Q. So I can be clear. Now are you 4 saying that the DEN system contains data that was 5 input into the system, not only from the drug 6 epidemiology unit, but also from the records 7 coming from the international affiliates who also 8 had computer access into the DEN system? 9 A. Right. 10 Q. Now, was the information that 11 was supplied from the international affiliates 12 that was initially entered into the DEN system 13 reviewed, analyzed, colated, in any way by 14 members of the drug epidemiology unit? 15 A. Yes. 16 Q. Would they make any 17 determination concerning whether or not 18 particular data would go into the DEN? 19 A. No, the data went into DEN in 20 any event. 21 Q. Regardless of whether or not 22 the members of the drug epidemiology unit felt 23 like it met the criteria? 24 A. That's correct. And the intent Page 166 1 was to -- the intent was to assure that if 2 someone sent a report in, that report would go 3 into the FDA if nobody did anything with it. But 4 then they would have to evaluate that information 5 as well. 6 Q. What do you mean but they would 7 have to evaluate that information as well? 8 A. The information would go from 9 the international affiliate would be put into 10 DEN, and a determination would need to be made 11 relative to the seriousness or expectedness of 12 that event that was put in by affiliate. 13 However, if for some reason someone didn't deal 14 with that, it would go in in a worse case 15 scenario. So the intent was to assure that we 16 always got things reported to the FDA in a timely 17 fashion. 18 Q. Were there different 19 requirements concerning not only whether or not a 20 particular event had to be reported to the FDA, 21 but also requirements concerning when that should 22 be reported or a time limit within which to 23 report it to the Food and Drug Administration? 24 A. Yes. Page 167 1 Q. Define for me what the 2 different parameters were on that? 3 A. Okay, I'll try. On spontaneous 4 reports, if the event was serious by the FDA 5 definition, it may not be relevant to a lay 6 person's terminology, but if it met the FDA 7 requirements on seriousness, and it also met the 8 requirements on expectedness, in other words if 9 it was unexpected, then that report, as a 10 spontaneous report, would go into the FDA within 11 fifteen days from the time we were made aware of 12 it. 13 Q. That's if it's a spontaneous -- 14 A. Serious, unexpected event. 15 Q. All right. What if there is an 16 event that occurs during an -- all right. And 17 that would be true whether or not it occurred in 18 a trial or spontaneous? 19 A. That's only spontaneous. The 20 requirements for trial are different. 21 Q. What is the requirement for 22 trial? 23 A. Trial would have requirements 24 for seriousness. They're fairly close to what Page 168 1 they are for spontaneous, the serious definition. 2 They, too, would have to be unexpected. But on 3 top of that, there was also a definition that 4 they had to be reasonably possibly related to the 5 drug. 6 MS. ZETTLER: Is that for clinical 7 trial adverse events? 8 THE WITNESS: That's correct. 9 MR. RUIZ: Did you say clinically 10 related? 11 THE WITNESS: Reasonably possibly 12 related to the drug if it was in a clinical 13 trial. 14 MR. RUIZ: Thank you. 15 Q. So when was that -- when would 16 that have to be reported? 17 A. That has to be reported in 18 paper within ten days. If it had to do with 19 life-threatening or death, it also needed to have 20 a call into the FDA within three days. 21 Q. So spontaneous reports, those 22 reports that you received -- I guess from the 23 majority of them would be from DISTA Lilly sales 24 reps. If they're serious and unexpected, as Page 169 1 defined by the Food and Drug Administration 2 regulations, they must be filed with the Food and 3 Drug Administration within fifteen days? 4 A. That's correct. 5 Q. However, if there is an adverse 6 event that occurs during a clinical trial, and 7 that adverse event is serious and unexpected and 8 is reasonably possibly related to the drug, then 9 that event must be reported on paper to the Food 10 and Drug Administration within ten days; correct? 11 A. Right. 12 Q. And if that event is in 13 addition to the other criteria, life-threatening 14 or involves a death, then the Food and Drug 15 Administration requires that Lilly submit a call 16 to the FDA within three days? 17 A. That's correct. 18 Q. If a call like that is made 19 during an event, during a clinical trial, is 20 there some record made by Lilly to confirm that 21 indeed the call was made? 22 A. To confirm in our own record? 23 Q. Yes. 24 A. Yes. Page 170 1 Q. What is done, how is that done? 2 A. As I recall, and I'm trying to 3 pull my memory, I think that we normally would 4 put that into the 1639. But if it were not put 5 into the 1639, we would put it on the document 6 where we took the initial record down. 7 Q. All right. Would you follow-up 8 with a specific memo to the file or memo within 9 the drug epidemiology unit saying I received a 10 report of life-threatening or death occurring 11 during a clinical trial at 12:47 a.m. on Monday, 12 June 15, 1990, and I contacted Mister so and so 13 at the Food and Drug Administration to report to 14 him this event? 15 A. It would be put into the record 16 for that file. What I don't recall is whether we 17 would just put it into the 1639, which meant it 18 was part of that record, or whether we would have 19 it as a part of the original document when we 20 wrote the information down. 21 Q. But Lilly would want to do 22 something to -- 23 A. Prove that. 24 Q. -- to satisfy if there were Page 171 1 ever a question that this call was indeed made, 2 would they not? 3 A. Right, correct. 4 MR. SMITH: Let's take a quick break. 5 (A SHORT RECESS WAS TAKEN.) 6 Q. Those reporting requirements in 7 connection with time within which you should 8 report an adverse experience with a particular 9 drug are different to some extent in connection 10 with respect to whether or not that report is 11 spontaneous or occurs during a trial. 12 A. That's correct. 13 Q. Could there be an incidence 14 where you would receive a spontaneous report and 15 a report of an adverse event that occurred during 16 the trial, during the clinical trial, in 17 connection with the same event? Let's say for 18 instance you had an individual who was in a 19 clinical trial. 20 A. Okay. 21 Q. And they attempted suicide, put 22 a gun to their head. 23 A. In a trial, okay. 24 Q. And was taken to a hospital one Page 172 1 evening, and the emergency room physician may 2 have called Lilly because this individual was on 3 Prozac. 4 A. Uh-huh. 5 Q. Then it was also learned that 6 that individual, maybe the next day, or the 7 investigator subsequently learned that that 8 individual was the same individual. 9 A. Yes. 10 Q. Did that ever occur while you 11 were in the drug epidemiology unit? 12 A. I think that it has. I don't 13 know if one was reported as spontaneous or one 14 that was a trial, I know that we have had 15 duplicate reports going into the agent, because 16 we weren't able to discern at the time because of 17 where the information came from that it was 18 indeed the same event. So, therefore, there 19 might be a duplication, and we would find out 20 subsequent to that that it was the same patient. 21 Q. The individual that -- does the 22 individual who receives the spontaneous report in 23 the drug epidemiology unit have access to a 24 listing of individuals in a particular location Page 173 1 who are involved in clinical trials? 2 A. No. 3 Q. Doesn't the clinical trial data 4 base have names of individuals enrolled in 5 clinical trials? 6 A. I don't recall that there's -- 7 well, I'm not really much of an expert on the 8 clinical trial data base. 9 Q. All right. Possibly the 10 clinical trial data base does have names of 11 individuals? 12 A. It could be coded, I'm not 13 sure. 14 Q. How is serious defined in 15 connection with a spontaneous report? 16 A. Death, life-threatening, 17 congenital anomaly, cancer, hospitalization. I 18 don't think I gave that one, did I, those are the 19 ones I recall. 20 Q. Well, think and make sure that 21 you're reasonably sure that you got all that you 22 can recall at this time. 23 A. Those are the five that I can 24 remember, I can't remember if there's any more Page 174 1 beyond that or not. 2 MS. ZETTLER: Overdose? 3 THE WITNESS: Overdose, yes, true. 4 Q. All right. Any others? 5 A. That's all I can recall. 6 Q. That's serious in connection 7 with spontaneous reports? 8 A. Uh-huh. 9 MR. MYERS: Yes. 10 A. Yes. 11 Q. Now, obviously death doesn't 12 need definition in connection with these six 13 items, but maybe life-threatening may need some 14 definition. Is life-threatening defined or 15 described in any way in connection with 16 determining whether or not something is 17 life-threatening? 18 A. Yes, it is, and I don't recall 19 now what that -- what that term -- what the term 20 or what the definition of that was that was 21 applied to it. 22 Q. But there was a consistent 23 definition applied to life-threatening? 24 A. As I recall, yes. Page 175 1 Q. What's your best recollection 2 of what that application was? 3 A. That the person's life was in 4 eminent danger, somewhere in that ballpark. 5 Q. Was congenital anomaly defined? 6 A. Yes, yes. 7 Q. How was it defined? 8 A. Congenital anomaly would be 9 somewhere -- generally being a birth defect. 10 MR. MYERS: Paul, when you asked him 11 was it defined, do you mean in the regulations? 12 MR. SMITH: Either in the regulations 13 or was there some consistent definition applied 14 by Lilly. And maybe we ought to straighten that 15 out. 16 Q. These definitions that you're 17 giving me are in connection with serious 18 spontaneous reports; correct? 19 A. Yes. 20 Q. And the six items that you 21 listed, are those Food and Drug Administration 22 items that constitute serious events? 23 A. The only way I can answer that 24 is to say that if we had a different definition, Page 176 1 it would be more of a tighter definition than 2 what the FDA had. If the FDA's was more general, 3 we would make it more broader in terms of its 4 definition. I don't recall the specific 5 definitions, honestly. 6 Q. Theoretically, if definitions 7 differed, your definitions should encompass more 8 events than that of the Food and Drug 9 Administration? 10 A. That's correct. 11 Q. Was cancer defined? 12 A. Cancer is cancer. 13 Q. Hospitalization, was it 14 defined? 15 A. Yes, the patient was either 16 hospitalized because of the event or their 17 hospitalization was prolonged if they were 18 already in the hospital. 19 Q. Was overdose defined? 20 A. Yes. 21 Q. How? 22 A. I don't recall now the specific 23 definition on overdose, other than the fact that 24 something happened and the patient took more than Page 177 1 what was prescribed. 2 Q. Was overdose defined as more 3 than the prescribed dosage? 4 A. I can't recall now what our 5 definition on that has been, it's been too long. 6 Q. Does the patient intent have 7 anything to do with whether or not the act comes 8 within the definition of overdose? 9 A. It might have, but I can't 10 recall. 11 Q. Does whether or not the 12 overdose is accidental or intentional have 13 anything to do with whether or not a particular 14 event meets the definition of overdose? 15 A. As I recall, that did not make 16 any difference. 17 Q. So accidental versus 18 intentional is immaterial? 19 A. Yes. As I recall it was, yes. 20 Q. Does whether or not the 21 overdose could cause physical harm from a medical 22 standpoint have anything to do with whether or 23 not the event is considered an overdose? 24 A. I don't believe that it does. Page 178 1 It seemed to me that if it was an overdose, 2 regardless of what happened after the fact, it 3 still would be reported. 4 Q. No, specifically I might take 5 ten aspirin -- 6 A. Okay. 7 Q. -- in attempt to harm myself. 8 A. Right. 9 Q. But from a medical standpoint -- 10 that might be my intent to harm myself, but from 11 a medical standpoint, you could probably be 12 pretty well recognized that ten aspirin normally 13 is not going to be lethal to an adult. 14 A. Right. 15 Q. So my question is: Does 16 whether or not the overdose presents any medical 17 harm have anything to do with whether or not you 18 characterize -- whether or not it is an overdose 19 for reported purposes? 20 A. No, we're strictly dealing here 21 with regulatory definitions, not medical. This 22 is a regulatory definition. If it's an overdose, 23 then regardless of what the consequences are, 24 then it has fulfilled that part of the Page 179 1 definition. 2 Q. All right. Have we covered all 3 of what would be included in defining or in 4 characterizing serious, as that term is used in 5 connection with reporting of a spontaneously 6 received -- in reporting a spontaneous adverse 7 event? 8 A. You're asking did we cover all 9 the various types of seriousness, is that what 10 your question is? 11 Q. Yes. 12 A. I believe we have. 13 Q. Now, you mentioned either 14 expected or unexpected in connection with whether 15 or not you had to report an adverse event 16 received spontaneously within fifteen days to the 17 Food and Drug Administration? 18 A. Right. 19 Q. In other words, it's got to be 20 serious and unexpected, is that right? 21 A. As a spontaneous report, right. 22 Q. How is unexpected defined? 23 A. Unexpected would be defined as -- 24 expected would be what is in the label, Page 180 1 unexpected would not be in the label. 2 Q. When you say label, what are 3 you talking about? 4 A. Package literature. 5 Q. Package literature? 6 A. Package insert. 7 Q. The package insert? 8 A. Right. 9 Q. And that is the physically 10 folded up package that goes in a container of the 11 medication? 12 A. Correct. 13 Q. That is shipped from Lilly? 14 A. Right. 15 Q. Is that the same information 16 that's contained in the Physician's Desk 17 Reference? 18 A. Generally, yes. The Physican's 19 Desk Reference, however, can become more 20 outdated. 21 Q. The Physician's Desk Reference 22 is published on an annual basis? 23 A. Once a year, right. 24 Q. By Medical Economic Publishing Page 181 1 group or something. 2 A. Somebody, right. 3 Q. But Lilly is responsible for 4 publishing package inserts, and they're 5 responsible for updating the package insert as 6 those insert updates are required by the Food and 7 Drug Administration, is that right? 8 A. Say that again -- we're 9 required to put it into the package insert of the 10 product. 11 Q. Yes. 12 A. Right. 13 Q. And what is in the package 14 insert has to be approved and required by the 15 Food and Drug Administration? 16 A. Yes. 17 Q. And if the Food and Drug 18 Administration requires that you change your 19 package insert, it must be done in a specific 20 period of time, it must be packed in a product 21 leaving Lilly by a certain date; correct? 22 A. I don't know that there's any -- 23 I would have to get refreshed on any -- on 24 whatever the specific timing requirements are. Page 182 1 Q. Whatever the requirements are, 2 they, certainly, in many instances, could be a 3 shorter timing than that timing of the 4 publication of the Physican's Desk Reference. 5 A. That's correct, right. 6 Q. Any particular package insert 7 should be more timely in connection with updating 8 this than a Physican's Desk Reference. 9 A. Unless they happen to 10 simultaneously be coming out at the same time. 11 Q. And that would just be a 12 coincidence. 13 A. That's correct. 14 Q. Now, when you say it's expected 15 if it's in the package insert, it's unexpected if 16 it's not in the package insert? 17 A. Correct. 18 Q. There's a lot of stuff in the 19 package insert. 20 A. Right. 21 Q. Now what in the package insert 22 are you looking at when you make the 23 determination concerning whether or not something 24 was expected or unexpected? Page 183 1 A. Well, you look into the adverse 2 effects, and if it says rash, and you have rash, 3 that would be expected. If you get a report of 4 rash and it's not in the package literature, then 5 that would be unexpected. 6 Q. Okay. So you look under the 7 adverse reaction section. 8 A. Primarily, yes. 9 Q. Any other sections that you 10 look at? 11 A. Could look at warnings. 12 Q. What else? 13 A. I can't recall now whether that 14 would also include the precautions section as 15 well. 16 Q. Now are there regulations that 17 define what to look at in the package insert in 18 making a determination whether something is 19 expected or unexpected? 20 A. Give me the question one more 21 time. 22 Q. Are there regulations that 23 define what you look at in the package insert in 24 making the determination with respect to whether Page 184 1 or not a particular reaction is expected or 2 unexpected? 3 A. I don't recall that there is, 4 but it's -- again, it's been a while. 5 Q. And again, when we're talking 6 about serious and unexpected, we're talking about 7 requirements with respect to spontaneous reports 8 received that must be filed with the Food and 9 Drug Administration within fifteen days, is that 10 right? 11 A. If they fulfill those 12 requirements, correct. 13 Q. If they fulfill those 14 requirements, what occurs? 15 A. They're submitted to the FDA 16 within fifteen days. 17 Q. How are they submitted to the 18 FDA? 19 A. In a fifteen -- or FDA fifteen -- 20 1639 type document. 21 Q. Is it the 1639 or is it the 22 1639 type document? 23 A. There was also another form -- 24 there was a different format that looked very Page 185 1 similar to the 1639 that was something that was 2 used for international that the FDA had 3 authorized as well. But they look very much the 4 same, they're just a little bit different. 5 Q. What is that called? 6 A. I think it was called -- an 7 acronym was called a CIOMS form. 8 Q. What does that stand for? 9 A. I don't remember. It was an 10 agreement between various regulatory agencies to 11 interchange information so those reports, when 12 they were submitted, would not only go to the 13 FDA, they would also be submitted in that format 14 to foreign agencies as well. 15 Q. But that had only to do with 16 international? 17 A. Right, reports occurring 18 outside would go in. 19 Q. OUS reports? 20 A. Yes. 21 Q. Now, let's go through those 22 requirements that require a three-day call -- 23 that require paper. First, that require those 24 paper ten-day reports which have to do with Page 186 1 adverse events that occur during trials -- 2 A. Uh-huh. 3 Q. -- clinical trials, that are 4 serious and unexpected and reasonably related to 5 the drug; correct? 6 A. Right. 7 Q. Now, is the definition of 8 serious in connection with ten-day paper, 9 three-day -- in connection with ten-day paper 10 reports any different than those that we 11 discussed earlier in connection with the 12 spontaneous reports? 13 A. Is there any difference -- say 14 that again. Is there any difference between the 15 reports going in that are submitted under ten 16 days versus those fifteen days? 17 Q. With respect to the definition 18 of serious. 19 A. Generally, that is -- generally 20 that is true, but as I recall, there also can be 21 reports that, based upon animal data, that would 22 also have to go in within a ten-day period. 23 Q. Give me an example. 24 A. Let's say rats died. Page 187 1 Q. All right, okay. So I can 2 understand, even if you had a report of an 3 adverse event that occurred during a clinical 4 trial -- 5 A. Okay. 6 Q. -- then you have to make a 7 determination with respect to whether or not it's 8 going to be -- have to be submitted in ten days 9 as opposed to fifteen days; correct? 10 A. Right. 11 Q. So you are going to have to 12 look at whether or not it's serious again. 13 A. Right. 14 Q. Do you look at that definition 15 of serious any differently than you do in 16 connection with the spontaneous reports? 17 A. As I recall, I think those 18 definitions were fairly much the same. There may 19 have been some deviations or I would have to go 20 back and look at the IND regulations or the NDA 21 regulations to discern what that difference was 22 because it has been awhile. But there was a 23 match up between hospitalization and death and 24 life-threatening and congenital anomaly and all Page 188 1 of those, as I recall, were also on the IND side 2 which affected trials. 3 Q. I have, in your definition of 4 serious that you've given us earlier in 5 connection with spontaneous reports, death, 6 life-threatening, congenital anomaly, cancer, 7 hospitalization and overdose. 8 A. Right. 9 Q. Now would there be any 10 additional events that would be considered 11 serious in the events analyzed in the clinical 12 trial data? 13 A. Not that I can recall in 14 clinical trial data. 15 Q. And the definitions with 16 respect to each four of those -- or each six of 17 those issues would be the same also? 18 A. The last I recall, they were. 19 You have to understand that those regulations 20 were promulgated at different times. The NDA 21 regs came out in '85, the IND regs came out in 22 '87. But I believe that they are harmonized 23 some. 24 Q. Okay. In any event, if there Page 189 1 is any definition that's different, that's being 2 applied by Lilly than the Food and Drug 3 Administration, that definition applied by Lilly 4 is going to be applied so that it will include 5 more rather than less? 6 A. That's true, it would be more 7 conservative. 8 Q. More conservative would cause 9 you to include more -- 10 A. More reports that might not 11 necessarily even qualify. 12 Q. Right. The next criteria in 13 analyzing whether or not a trial event is going 14 to be reported within ten days, is whether or not 15 it's unexpected or expected? 16 A. Right. 17 Q. Any difference in the 18 definition of expected and unexpected than that 19 that you've previously described to us in making 20 the analysis with respect to spontaneous reports? 21 A. If the drug is not on the 22 market or in the U.S., then obviously we would 23 not have the package literature, in which case we 24 would use the clinical investigation brochure. Page 190 1 Q. All right. To determine 2 whether or not the event is expected or 3 unexpected? 4 A. That's correct. 5 Q. And the clinical investigation 6 brochure, what portions of it would you look to? 7 A. It's layout, as I recall, is 8 very similar to the package literature format, 9 and, so, as I recall, we have adverse effects 10 kinds of things in there as well, and we've got 11 warning sections, too. It's just a little bit 12 bigger of a document. 13 Q. The clinical investigating 14 investigator brochure that I've seen in 15 connection with Fluoxetine is a five-inch 16 document. 17 A. Yes. 18 Q. Is that your recollection of 19 how thick the one is? 20 A. I don't remember having seen 21 how big it was, but that doesn't surprise me that 22 it would be that big. 23 Q. In fact, it's my recollection 24 is that clinical investigator brochure has Page 191 1 compilations of scientific articles on a 2 particular subject of Fluoxetine. 3 A. We could have elected to put 4 some of those things in there, I haven't looked 5 at it. I don't think that's all required. 6 Q. But what I'm trying to get is, 7 what you're going to consider in that brochure 8 pretty well defined in connection with whether or 9 not it's expected or unexpected, what areas in 10 that brochure are you going to look at, anything 11 other than adverse reactions, warnings and 12 precautions? 13 A. Well, I have never really 14 looked at -- I've never really done that myself, 15 but I would assume that that's what the physician 16 would use in order to determine that, that's a 17 physician's call. 18 Q. As to whether or not it's 19 expected? 20 A. That's correct, they have to 21 make that decision. 22 Q. And that -- when you say that's 23 a physician's call, are you talking about the 24 clinical investigator at the site who is calling Page 192 1 in the event or are you talking about the 2 clinical research physician at Lilly who is 3 interpreting the event? 4 A. The research physician at Lilly 5 would make that call, but if the investigator 6 said that it was -- if they said that it was 7 caused by the drug, and the research physician, 8 even though they didn't feel that, it would 9 default to the most conservative case scenario on 10 the part of the decision process. 11 Q. I'm talking about unexpected or 12 expected, I'm not talking about whether or not -- 13 A. The research physician would 14 make that. 15 Q. The research physician at Lilly -- 16 A. Right. 17 Q. -- makes the call on whether 18 it's expected or unexpected. 19 A. Right. 20 Q. Not the clinical investigator 21 at the site. 22 A. Right. 23 Q. Now, the other requirement in 24 connection -- as I understand it, in connection Page 193 1 with the paper requirement that would be 2 submitted within an event -- a report of an event 3 be submitted within ten days, is that that event 4 be reasonably possibly related to the drug; is 5 that correct? 6 A. Right. 7 Q. And who makes the determination 8 concerning whether or not the event is reasonably 9 possibly related to the drug? 10 A. Research physician. 11 Q. The research physician at 12 Lilly? 13 A. Right. 14 Q. Not the clinical investigator 15 at the site of the clinical study. 16 A. Right. 17 Q. What does the research 18 physician at Lilly use in making the 19 determination concerning whether or not the event 20 is reasonably possibly related to the drug? 21 A. The information that is 22 available would help them to make that decision 23 or if they were unsure, they might get additional 24 information then from the investigative site. Page 194 1 Q. I'm talking about what factors, 2 what criteria, what analysis, the research 3 physician at Lilly uses in making the 4 determination concerning whether or not the event 5 is reasonably possibly related to the drug. 6 MR. MYERS: Before he answers, let me 7 object to the form only to the extent that that's 8 a medical question. If he knows some of the 9 factors, that's fine, but he can't speak to how 10 they go about it as a lay person. 11 MR. SMITH: I'm not asking him whether 12 or not a particular reaction is or is not 13 reasonably related medically to a particular 14 drug, I'm asking for the criteria or the analysis 15 that is used by the research physician at Lilly 16 in coming up with that decision one way or the 17 other. 18 MR. MYERS: I understand that, but it's 19 still a medical question. If you know, tell him. 20 A. No, I don't know that there is 21 any specific criteria that -- I don't think 22 there's any easy formula to do that is my 23 impression. 24 Q. Wouldn't you want some kind of Page 195 1 consistency in your research physician in making 2 a judgment in connection with a particular event 3 concerning whether or not it's related to the -- 4 A. I think the statement itself is 5 is it reasonably possibly related is basically 6 what it comes down to. 7 Q. Okay. Do you know of any 8 written documents that describe the criteria or 9 the elements or the factors that should be 10 considered by Lilly research physicians at the 11 Lilly headquarters in determining whether or not 12 the event is reasonably possibly related to the 13 drug? 14 A. I can't recall anything. It 15 seems like I saw something somewhere that talked 16 about the broad range of that interpretation, but 17 I don't recall what it might have been. 18 Q. Would that be a memo or 19 something concerning determining that? 20 A. It could have been, could have 21 been part of the policy. 22 Q. A memo or policy of what? 23 A. Policy in dealing with those 24 definitions that are provided by the FDA. Page 196 1 Q. What do you -- 2 A. Policy and procedures. 3 Q. Does the FDA have a policy and 4 procedure manual that they submit to drug 5 companies to give to their research physicians in 6 making this determination concerning whether or 7 not the event is reasonably related to the drug? 8 A. They have -- the FDA has 9 provided, obviously, the Code of Federal 10 Regulations, but there also have been handbooks 11 that I have seen that they've -- I don't know 12 what they're called, that they've distributed, 13 which give, I think maybe they're called 14 guidelines or something. 15 Q. These are specific guidelines 16 that you've seen -- 17 A. Yes. 18 Q. -- that are promulgated by the 19 Food and Drug Administration to assist the 20 research physician in making the determination 21 concerning whether or not a particular event is 22 reasonably possibly related to the drug under 23 study? 24 A. Right, that helps us to make -- Page 197 1 helps us to better understand those regulations 2 when they first came out. And from that, we 3 established what our policy or what our 4 constraints are. 5 Q. And have you seen that Lilly 6 policy procedures guideline? 7 A. Yes. 8 Q. That has evolved from the Food 9 and Drug Administration guideline? 10 A. Right, I have. 11 (A SHORT RECESS WAS TAKEN.) 12 Q. As I understand it from your 13 earlier description, Mister Noone, that there is 14 an additional requirement that if the event is 15 life-threatening or results in death, that a call 16 must be made within three days to the Food and 17 Drug Administration; is that right? 18 A. If it qualifies under the trial 19 IND requirements. 20 Q. What is the reason that the 21 Food and Drug Administration would require that 22 you call them concerning this particular 23 situation? 24 A. Well, you're studying the drug, Page 198 1 you're trying to learn about it, and therefore 2 the chances of gaining new knowledge is much 3 greater when the drug is in a trial than it is 4 after its marketed because you've got lots of 5 data that's been provided. Therefore, if you're 6 doing studies across many, many centers 7 throughout the country, and you have a death that 8 occurs, then it's important for you to notify the 9 FDA, it's also important that those investigators 10 be made aware of it. 11 Q. Well, is this requirement that 12 the FDA be called within three days a Food and 13 Drug Administration requirement? 14 A. Correct. 15 Q. Is this so they could possibly 16 halt further studies in connection with a 17 particular drug if they saw some particularly 18 harmful results? 19 A. Right, or that study. 20 Q. But there is no such 21 requirement for spontaneous reports in connection 22 with a drug that has already received FDA 23 approval to market? 24 A. That's correct, not a formal Page 199 1 requirement, right. 2 Q. Now, how does either Lilly or 3 the Food and Drug Administration define 4 life-threatening in connection with the 5 requirement that there be a three-day call? 6 A. Well, as I related further, I 7 don't remember what the specific definition that 8 has been provided on that. 9 Q. Well, you had defined 10 life-threatening in connection with the 11 requirements of when to report a spontaneous 12 serious life-threatening report -- 13 A. Right. 14 Q. -- as being a situation where 15 life is in eminent danger. 16 A. Yes. 17 Q. Is that right? 18 A. That was my terms in trying to 19 characterize my impression, I don't remember the 20 specific terms. 21 Q. But life in eminent danger is a 22 pretty accurate description of what the actual 23 definition is. 24 A. As I recall, yes. Page 200 1 Q. It may not say eminent, it may 2 be almost immediate or something of that nature, 3 but it's close. 4 A. Yes. 5 Q. Who makes the determination in 6 connection with whether or not the particular 7 event involves a live-threatening condition? 8 A. Research physicians. 9 Q. The research physician at 10 Lilly? 11 A. That's correct. 12 Q. As opposed to the clinical 13 investigator at the site? 14 A. That's correct. 15 Q. Or as opposed to possibly the 16 emergency room physician where the patient was 17 taken who happened to be -- 18 A. On the spontaneous side. 19 Q. Well, or it could be -- I 20 believe you said there might be a situation where 21 you had a duplication, and there was a 22 life-threatening event that occurred that was 23 reported spontaneously and was also just 24 coincidentally happened to be an individual who Page 201 1 was engaged in the clinical trial. 2 A. Right, you can only deal with 3 what you know about. If you know it's 4 spontaneous, you deal with it that way. If you 5 know that it's trial, you deal with it another 6 way. 7 Q. Now, these regulations and this 8 procedure with respect to speeded up reporting in 9 connection with trial adverse events, does that 10 have to do with trials that are occurring 11 post-marketing? 12 A. Give me the question one more 13 time to make sure I understand it. 14 Q. Does this procedure where you 15 have different reporting requirements in 16 connection with time in connection with clinical 17 trial events -- 18 A. Right. 19 Q. -- does it make any difference 20 whether or not the drug has been approved for 21 marketing or is the question whether or not it's 22 a clinical trial event? 23 A. As I recall, it does. There 24 are -- the post-marketing requirements are Page 202 1 different for a study after it's approved in the 2 U.S. 3 Q. All right. We've taken the 4 depositions of some physicians who were, at the 5 time, employed by Eli Lilly and Company, and I'll 6 tell you specifically, it was Doctor Stark, 7 Doctor Stark, Ph.D. 8 A. Oh, yes, right. 9 Q. But let me take you for sure to 10 Doctor Wernicke. Doctor Wernicke was a medical 11 monitor in connection with clinical trials of 12 Fluoxetine prior to its being approved by the 13 Food and Drug Administration, as I understand it. 14 Is that your recollection is that he was a 15 medical monitor? 16 A. It seems like he was in around 17 that time, yes. 18 Q. And he was responsible for 19 monitoring the progress of clinical trials as 20 well as monitoring some adverse events that 21 occurred during these clinical trials. Do you 22 understand, was that your recollection of what he 23 did? 24 A. That doesn't -- that's not at Page 203 1 odds that I can recall, but I'm not sure that he 2 and I were in interface functions at that time, 3 I'm not sure I can recall what his timing was at 4 that time. 5 Q. We've also taken the 6 depositions of some medical doctors who we 7 consider -- who call themselves clinical research 8 physicians. Doctor Kotsanos, for instance. 9 A. Uh-huh. 10 Q. You referred to, in connection 11 with your answer to my questions with respect to 12 these reporting procedures within the DEN or 13 within the drug epidemiology unit -- 14 A. Right. 15 Q. -- you used clinical 16 investigators -- I mean you used the term 17 research physicians at Lilly. 18 A. Right. 19 Q. Would there be any distinction 20 between a research physician at Lilly, such as 21 Doctor Kotsanos, with respect to making 22 determinations in connection with particular 23 adverse reactions and medical monitors, such as 24 Doctor Wernicke, in connection with making these Page 204 1 same determinations? 2 A. As I recall, they're all, in my 3 definition, research physicians. I do remember 4 Jim going in to some function at one time, and, 5 in fact, I think he's in that function now, and 6 it's something called pharmacoepidemiology. 7 That's not part of the drug epidemiology unit, 8 but he is a research physician that works in that 9 area. 10 Q. But when you had talked in 11 connection with my earlier questions, and spoke 12 of research physicians at Lilly, that could be an 13 individual who described himself as a research 14 physician at Lilly, such as Doctor Kotsanos, and 15 it might also include a physician such as Doctor 16 Wernicke that happened to have maybe had a title 17 of medical monitor in connection with a 18 particular -- 19 A. Right, whatever they're called, 20 they have been called a variety of different 21 titles. 22 Q. Now, I would like to go into a 23 discussion of sort of a step-by-step process of 24 what occurred within the drug epidemiology unit Page 205 1 when a report of an adverse reaction was 2 received. Let's use, for example, this hotline 3 that you said the majority of the calls came in 4 from detail individuals or sales reps; correct? 5 A. Yes. 6 Q. All right. Physically, let's 7 say, a sales rep reports that he called on a 8 physician, and a physician had reported an 9 adverse reaction to Fluoxetine -- 10 MR. MYERS: Or an experience or an 11 event. 12 Q. -- or event. 13 A. Uh-huh. 14 Q. What occurs physically from the 15 time the phone is picked up? 16 A. In that mode, the sales rep 17 calls the person who's handling that hotline, and 18 then that individual takes down the basic 19 information from the sales rep that they have 20 collected. 21 Q. All right. What basic 22 information is obtained? 23 A. I can give you parts of that, 24 I'm sure I can't remember all of the questions Page 206 1 that they would ask. But they would be 2 interested in knowing whether the patient died or 3 whether the patient was hospitalized or if we 4 knew anything else about the seriousness part of 5 it. The drug, understanding which drug it was, 6 and what the adverse event was that had occurred. 7 Q. Would there be anything else 8 obtained in that? 9 A. There could be. Those, as I 10 recall, were the key elements to cover, but if 11 the sales rep passed on other information, that 12 would also be taken down at that time. 13 Q. All right. Now, what is the 14 title of that individual that is monitoring the 15 phone? 16 A. That took the phone call, I 17 think we called them a drug epidemiology 18 assistant or something like that. Looks like we 19 call them regulatory affairs assistants as well. 20 Q. Now, in your memo that's been 21 marked as Exhibit 1, you mention four different 22 areas of division responsibility; correct? 23 A. Four different -- say it again? 24 Q. Divisions. Page 207 1 A. On page one, right. 2 Q. In connection with the 3 organization of the unit? 4 A. Right. 5 Q. Now, would any one of these 6 regulatory affairs assistants pick up the phone? 7 A. The people on the second page 8 would be the ones that would typically pick up 9 the phone. 10 Q. All right. So they're not 11 divided by chemotherapy or internal medicine or 12 neurosciences? 13 A. That's correct. 14 Q. They don't have any particular 15 training in any particular area? 16 A. Their job was to take down all 17 the information that had been collected by the 18 sales representative, they were not to interpret 19 or to make any judgment, they just took down all 20 the information, they have some of those areas 21 that they would cover about the seriousness and 22 whether the patient had died or hospitalized, and 23 what was the event that had been reported. 24 Q. Did they have a particular Page 208 1 checklist or form that they had to complete? 2 A. As I recall, and it's testing 3 my memory to probably beyond its stretch, but 4 they were instructed to cover the areas that I 5 had told you before, and I can't remember whether 6 it was on the formatted sheet that they wrote the 7 information down on or whether they had another 8 card they referenced to make sure they took that 9 down. 10 Q. I just wonder if -- do they 11 write it down on a yellow pad, yellow legal pad, 12 or did they have a telephone message slip or was 13 there some specific form that they had in front 14 of them? 15 A. Sometimes they would just 16 automatically key the information right into the 17 DEN system at that point. Other times, depending 18 on the expansiveness of the input, they would 19 write it down. 20 Q. Would they write it down if 21 there was more information obtained or would they 22 computer entry it if there was more information 23 obtained? 24 A. If there was more information Page 209 1 provided on the up-front end, then they would 2 probably write the information down. If it was 3 just a limited amount of information, and they 4 could quickly key that in, then we would already 5 have it in the system. 6 Q. Would there be any difference 7 in what occurred with the information in the next 8 step as to whether or not it was keyed into the 9 computer or written out? 10 A. The next step would be to key 11 the information into the computer. Whether they 12 took it down handwritten or they keyed -- they 13 can either key it in when they're taking the call 14 or handwrite it. If they handwrite it, before 15 they do anything more with it, then they could 16 key it in after they hung up the phone. 17 Q. Did they keep any records of 18 their handwritten notes after they keyed it in? 19 A. I don't remember what our 20 procedure was at that specific time. 21 Q. After it was keyed into the 22 system, what would happen next? 23 A. Next step would be for the CRA 24 for the given area -- so if it was chemotherapy, Page 210 1 then one of the clinical research administrators 2 then would review that information and would 3 determine at that point whether we need to gather 4 more information from the reporter. 5 Q. All right. Let's talk about 6 neuroscience since we're -- this lawsuit involves 7 Prozac, and it's a CNS type drug. Does this mean 8 that at least after November 17, 1989, after the 9 material is keyed into the system it would be 10 reviewed by Ms. Pearson, Donna Pearson or Jeff 11 Powell? 12 A. Normally, that's right. 13 Q. Now, how do they know to look 14 at it rather than one of these other individuals, 15 clinical research administrators in other 16 divisions? 17 A. How do they know, because it's 18 just given to them. 19 Q. How does the regulatory affairs 20 assistant know to give it to them? 21 A. Well, she would know that the 22 product is in the category of neuroscience, and 23 therefore it's given to Pearson or Powell if 24 they're the ones that are there. But all the Page 211 1 CRAs, because of vacations or whatever, would 2 also be cross-trained, so if one of them didn't 3 happen to be there, then somebody else could 4 handle it as well, but the intent of this was to 5 have Pearson and Powell handling the products in 6 the neurosciences end. 7 Q. And consequently they would be 8 handling most of these calls on Prozac. 9 A. That's correct. 10 Q. Which in October, 1983 were 11 running fifty-three percent of the calls? 12 A. Uh-huh. 13 Q. Now what type of training did 14 Donna Pearson and Jeff Powell have in October of 15 1989? 16 A. Their training is -- Donna, as 17 I recall, is a nurse, and Jeff is a pharmacist. 18 So that's their educational training. 19 Q. Where are Ms. Pearson and 20 Mister Powell now, are they still Lilly 21 employees? 22 A. Yes, they are. 23 Q. Are they still in the drug 24 epidemiology unit? Page 212 1 A. I know Mister Powell is not, 2 he's moved to another assignment in the medical 3 division. Ms. Pearson has -- I think she's just 4 returned from maternity leave. I'm not sure 5 whether she's still in the drug epidemiology unit 6 or not, she might have just moved. 7 Q. Do you know what job function 8 Mister Powell has now? 9 A. He's a clinical research 10 administrator in working one of our new 11 developing compounds. 12 Q. Is it the new antidepressant? 13 A. No. 14 Q. Is it a CNS drug? 15 A. You could probably categorize 16 it in that way. 17 Q. What's it used to treat? 18 A. I don't think I want to answer 19 that. I don't think I can, I really believe 20 that's proprietary information. 21 MR. MYERS: If that's what you think, 22 then you don't have to tell him, if that's what 23 you believe. 24 MS. ZETTLER: Are you a lawyer, Mister Page 213 1 Noone? 2 THE WITNESS: No. 3 MR. MYERS: One person at a time, 4 please. 5 Q. You don't know what proprietary 6 information is, do you? 7 A. Yes, I do. 8 Q. By virtue of what? 9 A. By virtue of my making 10 presentations to groups outside the company and 11 what I have to have reviewed and what I can say, 12 in protection of the company, and certainly not 13 to get us into any issues with the SEC. So 14 there's things that are very important to us that 15 we can't disclose to the outside. 16 Q. Well, we're under a protective 17 order in connection with disclosure of documents 18 and information in connection with this case, and 19 your attorneys can take whatever, and have taken, 20 appropriate steps to protect the company from 21 release of proprietary information. My question 22 is, and I think it's significant to know, what 23 usage the compound is that Mister Powell is 24 working on now. Page 214 1 MR. MYERS: Don't tell him, Mister 2 Noone, that is proprietary and I'm going to 3 instruct him not to answer. I don't know if you 4 noticed, but when Mister Powell testified ad 5 nauseum over the course of a day about his 6 responsibilities, but Mister Noone is not going 7 to testify about what Mister Powell is now doing. 8 You know all you need to know about Mister 9 Powell. 10 MS. ZETTLER: That was funny, Larry -- 11 MR. SMITH: I find that sort of 12 offensive. 13 MS. ZETTLER: -- working on any 14 compound other than Fluoxetine during his 15 deposition. 16 MR. SMITH: I find that sort of 17 offensive, that Mr. Myers is telling me I know 18 all I need to know about a particular subject. 19 MR. MYERS: I'm not sorry, but I 20 regreet that you're offended. 21 Q. All right. What would Mister 22 Powell or Mrs. Pearson's function be once they 23 received from the regulatory assistant the 24 information? Page 215 1 A. They would look basically at 2 the information to see if there was more 3 information that might be required in terms of 4 follow-up, in calling the original reporter, not 5 the sales representative, but the person who 6 originally reported the event. 7 Q. Well, now, the three basic 8 things that you told me that were received at the 9 time the initial call, was whether or not the 10 patient died or was hospitalized -- 11 A. Right. 12 Q. -- the particular drug that was 13 involved, and the nature of the adverse event. 14 A. Right. 15 Q. You didn't tell me that they 16 also secured the name of the physician from whom 17 the event was linked. 18 A. Yes, I must have omitted that. 19 It might not be a physician, by the way. 20 Q. Well, who might else it be? 21 A. It could have been -- could be 22 a paramedical person, could be a nurse, could be 23 a doctor of osteopathy. 24 Q. They call themselves physicians Page 216 1 also. 2 A. Some people refer to them as 3 physicians, others don't, but that's beside the 4 point. 5 Q. So it's the CRA that makes the 6 initial decision concerning whether or not a 7 follow-up needs to be obtained in connection with 8 getting more information regarding a particular 9 event? 10 A. They would make the first 11 decision on that, correct. 12 Q. What guidelines do the CRAs 13 have in making the determination concerning 14 whether or not a follow-up is needed on a 15 particular event? 16 A. A lot of it would just, as I 17 recall, had to do with their understanding, how 18 long they had been in the area, and just looking 19 at the report to see if there is a limited amount 20 of information. Obviously if the event did not 21 require hospitalization, didn't fulfill any of 22 the serious requirements, and was expected 23 according to label, then it may be that there 24 would not be any additional follow-up. But they Page 217 1 would look at the factors that were on the page 2 as they were reported. 3 Q. What if they decided there was 4 no need for additional follow-up, what would 5 happen after that? 6 A. Then the report would be -- 7 they would either pass that report on down as it 8 was to the physician, and the physician then 9 would have to assign the expectedness of the 10 report, review it, and then it would come back to 11 the drug epidemiology unit. 12 Q. Why would a physician be seeing 13 the report if it was determined by the CRA that 14 the event was not serious? 15 A. Well, it's really a 16 double-check to begin with. 17 Q. Okay. 18 A. So it was a matter that the 19 physician had to really sign off on the report. 20 Q. The clinical research 21 physician. 22 A. Right. 23 Q. Regardless of what a CRA might 24 or might not determine, is it your testimony that Page 218 1 a clinical research physician reviewed every 2 report of adverse events reported to Eli Lilly 3 and Company in connection with Fluoxetine? 4 A. As I recall it, yes. 5 Q. I need to -- I just thought of 6 something that I needed to ask you -- 7 A. Sure. 8 Q. -- that I forgot to. In 9 connection with these guidelines that you 10 mentioned that not only are they guidelines from 11 the FDA, but guidelines from Lilly, with respect 12 to whether or not an event is reasonably possibly 13 related to the drug. What would be the name of 14 the Lilly guidelines in connection with making 15 that determination? 16 A. I believe that was included in 17 a policy, practices, procedures books. 18 Q. Policy, practices, procedures. 19 Now is that policy, practices and procedure for 20 the drug epidemiology unit, for the medical 21 division, for clinical research, for Lilly 22 Laboratories, Inc., what is the policy, practice 23 and procedures manual? 24 A. It's comprised of various Page 219 1 chapters that deal with how we conduct business 2 in the medical division. 3 Q. But it's a medical division 4 only policy and procedures manual? 5 A. That's correct. 6 Q. It doesn't have anything to do 7 with marketing? 8 A. With marketing -- 9 Q. Doesn't have any marketing 10 strategies, does it? 11 A. No. 12 Q. It doesn't have any information 13 in it concerning actual budgets that are being 14 used with respect to any particular clinical 15 trial, does it? 16 A. It would have -- yes, it would 17 have information on how we go about doing budgets 18 for clinical trials, yes. 19 Q. But it wouldn't have specific 20 budget information concerning any -- the cost of 21 any particular trial? 22 A. I don't remember that it did 23 that, no. 24 Q. It's just a policy, practices Page 220 1 and procedures manual. 2 A. Right. 3 Q. And it's designed for the 4 medical division -- 5 A. That's correct. 6 Q. -- at Lilly Research Labs. 7 A. Right. 8 Q. And that manual is going to 9 have the guidelines that the research physician 10 at Lilly is going to use in determining whether 11 or not an event is reasonably possibly related to 12 the drug; correct? 13 A. I would say most of the 14 information would be there, yes. 15 MR. MYERS: Excuse me, I'm sorry, let's 16 go off the record for a second. 17 (DISCUSSION OFF THE RECORD.) 18 Q. Do you recall what the federal 19 guidelines are or do they have any particular 20 name in connection with the criteria to be used 21 in determining whether or not an event is 22 reasonably possibly related to the drug? 23 A. Well, the starting document is 24 the Code of Federal Regulations is what's used. Page 221 1 Q. Any particular heading or 2 subheading that would help me? 3 A. It's three something, but I 4 don't remember now what the -- which -- where the 5 NDA regulations were. Three twelve was IND, but 6 I'm not sure what NDA was. 7 MR. SMITH: Let's stop for the day. 8 * * * * * * * * * * 9 (THE DEPOSITION WAS ADJOURNED 10 UNTIL THE FOLLOWING MORNING, 11 10-20-93 AT 9:00 A.M. AT THAT 12 TIME, THE PROCEEDINGS CONTINUED 13 AS FOLLOWS:) 14 * * * * * * * * * * 15 Q. (BY MR. SMITH) Mister Noone, 16 yesterday when we adjourned we were talking about 17 the steps that were done within the drug 18 epidemiology unit in connection with reports of 19 adverse events with all drugs, I suppose, that 20 Lilly produces, but obviously our focus here is 21 on Prozac and Fluoxetine that might be used in 22 clinical trials. You had mentioned that a 23 clinical research administrator would receive the 24 documents or receive the information after it had Page 222 1 been keyed into the computer system; is that 2 correct? 3 A. In the mode that we discussed, 4 yes. 5 Q. And that the clinical research 6 assistants are given this information by the 7 clerical personnel that initially key it in. How 8 do they know to give it to a particular clinical 9 research administrator? 10 A. It was outlined on that sheet 11 that we had yesterday, it was identified who had 12 responsibilities for what therapeutic groups. 13 Q. I understand that, but if it 14 was on a computer. Let's say that there's an 15 entry made and it's simply a computer entry, some 16 could be handwritten and some entered directly on 17 the computer. Does the clerical individual make 18 a note that the clinical research assistant 19 should go punch in something in the computer to 20 get all the reports with respect to, say, 21 Fluoxetine that had come in over a period of 22 time? I don't understand how the clinical 23 research administrator who is handling Prozac 24 knows to go get the Prozac calls over a certain Page 223 1 period of time from the computer, do they just 2 punch in a key on a regular basis that brings 3 that information out? 4 A. As I recall, in the mode that 5 we discussed in which a sales rep called in and 6 the assistant took the information down, that 7 person would then just walk the information down 8 to that individual and give it to them. 9 Q. But I thought it would be 10 entered into a computer? 11 A. It is, that's true. 12 Q. She would go down and tell them -- 13 don't they each have a computer terminal? 14 A. Right, they would have. 15 Q. And does she tell them -- say 16 Mister Powell is one of the ones, I believe, Jeff 17 Powell that was handling Fluoxetine calls, would 18 she say Jeff, I just got a Fluoxetine or Prozac 19 call, I've already entered it into the computer, 20 now you punch it up? 21 A. I don't remember now, you know, 22 what the procedure was. They either would take 23 the paper that they had, the computer output, or 24 their notes or whatever, and that would be the Page 224 1 alert to the CRA to work with that given report. 2 Q. Obviously my concern is how do 3 you eliminate the possibilities of human error 4 where a clerical individual may have taken the 5 call, entered it into the computer or made a 6 handwritten notation of it, how do you ensure 7 that she gets it to the clinical research 8 administrator? 9 A. The system is set up as such 10 that once that report was put in, it would be 11 sent for mailing to the FDA if nobody did 12 anything with it. So that was the back up in the 13 event that, let's say, the person dropped dead on 14 the way back there. So they would take the 15 information back to the CRA. If for some unknown 16 reason that did not happen, then the system would 17 crank that out, and through our algorithm, that 18 report would be cranked out and be submitted to 19 the FDA with the information we have. 20 Q. Is it your testimony, then, 21 that once data is entered concerning an adverse 22 event onto your computer, that that computer 23 will, even if nothing else happens, no further 24 work is done, the thing is just stopped right Page 225 1 there, that at some point that computer is going 2 to generate some notice to the Food and Drug 3 Administration of that call or of that entry? 4 A. Yes. If the decisions are not 5 made on seriousness and expectedness, as I recall 6 it, then that report would automatically default 7 to be sent in alert timing. 8 Q. Would automatically be what? 9 A. Sent for, in terms of alert 10 timing, fifteen days if it's a spontaneous 11 report. 12 Q. And that would be in the form 13 of a 1639? 14 A. Correct, or CIOMS report if it 15 was from international. 16 Q. Now, the function that the 17 clinical research administrator does with that 18 report is makes an initial determination 19 concerning the seriousness and the expected 20 nature of the event? 21 A. They would look at the report 22 to see what the next step needed to be, and that 23 next step might be contacting the originating 24 reporter. Page 226 1 Q. Or? 2 A. Or passing the information on 3 to the research physician to conduct their 4 evaluation of the report. 5 Q. How does the CRA ensure that 6 the research physician sees each and every 7 report? 8 A. Well, it's basically the same 9 mechanism that we had talked about before, that 10 if that report did not get down to the research 11 physician or the CRA dropped dead or whatever, 12 there would be a default mechanism that that 13 report would kick out, and then it would be sent 14 to the FDA. As I recall, those reports that 15 didn't get touched would be flagged anyway, so 16 there would be a review of that information again 17 if for some reason that did happen. 18 Q. Is there some checklist that is 19 employed or was there a checklist employed at the 20 time that you were head of the DEU that ensured 21 that all of these steps were done in connection 22 with each particular event that was reported? 23 A. I don't recall a specific 24 checklist, but be more specific, if you could. Page 227 1 Q. Well, some checklist that 2 outlined the procedure for an adverse event from 3 the time it was received into the unit by the 4 clerical personnel all the way down to after it 5 had received its final work or, you know, the 6 last stage? 7 A. I can't remember specifically 8 what we had. I do remember that we had an 9 understanding and a procedure in place that 10 indicated what needed to occur, and then we had, 11 as I indicated before, the back up system that 12 once things were entered into DEN, they would 13 default to the worst case scenario of submission, 14 the most conservative approach. 15 Q. All right. So the event now 16 moves from the CRA to the research physician; 17 correct? 18 A. Right. 19 Q. And what does he do or she? 20 A. Well, then, as I recall, what 21 they did was to look at the report, make some 22 judgment about whether more information might be 23 needed, they would assess the seriousness and the 24 expectedness criteria, and perhaps have more Page 228 1 discussion with the CRA, determine what action 2 might be taken. If no further action was 3 necessary, then the report would be finalized and 4 then ultimately submitted to the agency, either 5 immediately or in the time line that was 6 specified according to the FDA regulations. 7 Q. Let's assume that the research 8 physician felt that at the time he reviewed the 9 report that there was additional information, and 10 I assume he had the option to follow-up himself 11 to secure the additional information that was 12 needed; is that correct? 13 A. True. 14 Q. And do you know of instances 15 where that was done, where the research physician 16 himself maybe called the treating physician, the 17 hospital or the individual concerned? 18 A. I recall that yes, that was 19 done, right. 20 Q. Or let's assume that the 21 research physician requested that the CRA get 22 this follow-up information. What checklist or 23 guidelines or procedures were in place to ensure 24 that the instructions to the CRA were completed Page 229 1 and that the event report got back to the 2 research physician? 3 A. Well, first off they would have 4 a discussion about what needed to take place, and 5 that was really a medical kind of decision that 6 was tied into regulatory need. There was no 7 specific checklist, as I recall, that relate to 8 all of that because I think there's just so many 9 things that could be taken into consideration. 10 The follow-up would be done, and I'm not sure I 11 can even recall how they would have a 12 confirmation that the follow-up was done, 13 although if for some reason that were not done, 14 then they would be aware of that later on through 15 other reports that were generated, they would 16 have a chance to review that. You review the 17 reports on an ongoing kind of basis to see what 18 the status of your adverse event reports are. 19 Q. Would that be because the 20 computer would automatically keep kicking out 21 this information that a follow-up was necessary? 22 A. I don't remember that that was 23 the case, but I can't remember now what -- this 24 was a very sophisticated system, and I can't Page 230 1 recall all the details we had with each one of 2 those situations. 3 Q. After the research physician 4 had made his final determination concerning the 5 event, what occurred next? 6 A. Information would be put into 7 the system that that report was finalized. It 8 seems to me we also had a report -- getting back 9 to your other question, it seems we also had a 10 report that identified reports that had not been 11 finalized, getting back to your other question. 12 Q. Was the computer programmed in 13 such a manner that if a certain amount of 14 information was not met or was not compiled, that 15 it would automatically kick back and forth, in 16 other words you eliminated field three, we still 17 need field three before this can -- 18 A. Right, as I recall that's true, 19 yes. 20 Q. What type of computer was the 21 DEN system? 22 A. What type of computer was the 23 DEN system? 24 Q. Give me a description of the Page 231 1 hardware and software. 2 A. That would be beyond my scope. 3 I can briefly tell you that it resided on 4 something called an SA 400, and it was developed 5 by our in-house personnel, systems analyst. 6 Q. Was that computer efficient, 7 did you ever have any problems with it? 8 A. Define problems. 9 Q. Well, where you had periods of 10 time where it wasn't working like it should? 11 A. Oh, I think there were times 12 when yes, there were issues that would come up, 13 but we have back-up systems in place that would 14 assure that we met our regulatory timing. 15 Q. What kind of back-up systems 16 were involved? 17 A. You had paper back-up systems 18 as well as systems back-up as well. 19 Q. What kind of paper back-up 20 would there be in those instances where the 21 original report of the event was transcribed 22 directly onto the computer? 23 A. I can't recite what those were 24 at this point, it's too far removed in time. Page 232 1 That was back in the '88, '89 period. 2 Q. I thought you were involved up 3 through 1991? 4 A. Right, but a lot of the systems 5 that were put in place go back to the '88, '89 6 period. 7 Q. Tell me about the last system 8 that you had in place in connection with this. 9 If you're having a problem remembering in '88, 10 maybe if I moved up three years to 1991, you 11 wouldn't have so many problems in recalling that 12 information. 13 A. I'm still -- I'm not following 14 your question. 15 Q. I need to get from you what 16 information you have concerning back-ups, to 17 ensure that this data was received and properly 18 analyzed and properly reported, and you mentioned 19 that there were instances in which the initial 20 report would be transcribed directly onto a 21 computer. 22 A. Right. 23 Q. And I asked you what would 24 happen to ensure that that initial report, if you Page 233 1 had a problem with the computer, didn't get lost. 2 You said you had paper back-up, we had other 3 computer back-up systems in case our computer was 4 broken down. I need to know -- I need to have 5 some description of that back-up. 6 A. I really can't give you a 7 description of the back-up, I can tell you that I 8 cannot recall that we ever had a situation like 9 that ever come up, where something was put into 10 the system that we lost, I don't recall that ever 11 happening. 12 Q. Could this information on your 13 system be deleted? 14 A. Not to my knowledge. 15 Q. It was impossible to delete it? 16 A. Impossible is an interesting 17 term. I do remember that those questions were 18 asked and addressed as we went through various -- 19 any changes in the DEN system. My belief would 20 be that it would be impossible to do that, but I 21 can't tell you how since I'm not a systems person 22 at this point and I am removed in time based upon 23 all the discussions that we had on the system 24 when these developments were made. Page 234 1 Q. Do you have any recollection of 2 the term information being locking into the 3 computer? 4 A. Locking in meaning what? 5 Q. I would assume that the 6 individuals describing that meant that an 7 individual had to have a special key to access 8 that information to change it in any manner. 9 A. I'm not tracking what that 10 particular term -- if an issue came up where we 11 were having some sort of difficulty, we had 12 systems analysts on hand to help with those kinds 13 of questions or issues. 14 Q. I understand. Let me make it 15 maybe a little more direct. 16 A. Sure. 17 Q. Let's assume that the 18 plaintiffs in this lawsuit claimed that Lilly was 19 receiving information into their computer 20 concerning adverse events, and that Lilly 21 attempted to or did, in fact -- that the 22 information that Lilly is now relying on is 23 invalid because they had the ability to delete a 24 lot of information that they say they had Page 235 1 received, that the information that is being 2 provided through computer generated information 3 is faulty because individuals at Lilly deleted 4 important information, and had a course of 5 conduct in going through and deleting information 6 that they didn't like in their system. 7 A. Uh-huh. 8 Q. And you were the administrative 9 head of the drug epidemiology unit during that 10 time, during a period of time. 11 A. Right. 12 Q. What would be your response to 13 that allegation of I am the head -- I was the 14 head of the epidemiology unit, and I dispute that 15 that could occur because A, B, C. What would be 16 your reasoning to dispute our allegation that 17 individuals at Lilly deleted information from 18 their computers which would -- which they didn't 19 like? 20 MR. MYERS: Before he answers, let me 21 object to the form of the question slash 22 allegation, on the basis that it assumes numerous 23 facts which are not in evidence and which will 24 never been in evidence. But if he's able to Page 236 1 respond, go ahead. I think you understand what 2 he was driving at, he was rather direct. 3 MR. SMITH: I preceded it with a 4 comment that I was going to be direct. 5 A. I would say that those 6 questions had been asked throughout the course of 7 the development and changes that we put into the 8 system, and to my knowledge or to my 9 recollection, I don't recall that that could 10 occur. Now from a systems standpoint, I can't 11 explain to you how we were able to do that due to 12 A, my recollection of what was discussed at the 13 time, and certainly because of my background not 14 being one of a systems analyst in programming 15 those kinds of things. 16 Q. Well, do you dispute -- or let 17 me put it this way: Do you deny that you have 18 any knowledge that there was any deletions of 19 information in the Drug Experience Network while 20 you were the head of the drug epidemiology unit? 21 A. There were several negatives in 22 that, I'm not sure -- say that again, do I deny 23 that any -- 24 Q. You can repeat it -- Page 237 1 A. That's as far as I got. 2 Q. If I can clarify it, I will, 3 but we can also have the reporter read the 4 question back. 5 A. Yes, why don't you have her 6 read it back if you wish. 7 (THE COURT REPORTER READ BACK THE 8 REQUESTED TESTIMONY.) 9 A. Do I deny that I have any 10 knowledge that there was information deleted. I 11 have no knowledge that there was ever any 12 information that was deleted from the Drug 13 Experience Network system other than duplicate 14 reports which would be the same information. 15 Q. How would you go about deleting 16 duplicate reports from the system? 17 A. There was a special procedure, 18 as I recall, where you had to involve another 19 person or persons, and I don't remember how many, 20 before you could have that done. 21 Q. Can you give me the names of 22 the individuals while you were the head of the 23 drug epidemiology unit that you would have called 24 upon to perform this function of deleting Page 238 1 duplicity of information? 2 A. I never had any reports taken 3 care of myself, that was not my function. Some 4 of that would involve a CRA and the drug 5 experience -- or in the drug epidemiology unit, 6 and it would also involve, as I recall, the 7 person who was the DEN coordinator. 8 Q. Who was the DEN coordinator 9 while you were in charge of the DEU? 10 A. The last one that I remember 11 was probably Brenda Roach. 12 Q. Was she a systems analyst type 13 person? 14 A. No, she was trained in systems, 15 but she was in a coordinating function between 16 the user community and the systems people. 17 Q. You mean the user community of 18 the computer? 19 A. Right, the drug epidemiology 20 unit people primarily. 21 Q. Now is a 1639 filed on every 22 adverse event reported to Eli Lilly and Company? 23 MR. MYERS: Spontaneous or clinical 24 trials, because any -- Page 239 1 MR. SMITH: Any. 2 A. No. 3 Q. What events are not reported as 4 a 1639? 5 A. Reports that are conducted in a 6 study, an IND study, that would be categorized 7 non-serious according to regulatory definition. 8 Q. All right. Any other adverse 9 events that would not be reported to the Food and 10 Drug Administration as a 1639? 11 A. That's the one that sticks out 12 in my mind at this point, I can't recall that 13 there are any others. 14 Q. So any spontaneous event 15 received would be reported as a 1639 whether it 16 be serious or non-serious? 17 A. Yes, as I recall, that's true. 18 Q. The only exception that you 19 recall at this time with respect to instances in 20 which a 1639 would not be filed would be 21 instances where there was an event reported that 22 had occurred during a clinical study that was 23 determined to be non-serious; is that correct? 24 A. That's correct. Page 240 1 Q. The medical research physicians 2 that were making the final determination with 3 respect to each of these events were housed 4 physically in a different location from the drug 5 epidemiology unit, were they not? 6 A. They were not in the same room, 7 correct. 8 Q. Were they even in the same 9 building? 10 A. I think some were, some 11 weren't. 12 Q. While you were the head of the 13 drug epidemiology unit, can you list for me the 14 names of the clinical research physicians that 15 were responsible for handling adverse events in 16 connection with Prozac or Fluoxetine 17 Hydrochloride? 18 A. This is the 1988 period to 19 1992. It seemed to me that Doctor Street -- 20 Q. Jamie Street? 21 A. Yes, was. Doctor Wheadon. 22 Q. David Wheadon? 23 A. Yes. Probably Doctor Beasley, 24 probably Doctor Goldstein, and I think you Page 241 1 indicated yesterday that Doctor Kotsanos was as 2 well. 3 Q. Don't let me put words in your 4 mouth, if you don't have a recollection of him 5 being responsible for it -- 6 A. He might have been. That's all 7 that comes to mind to me during that period of 8 time. There may well have been other people, but 9 I'm not familiar who they might be. 10 Q. How about Doctor Heiligenstein? 11 A. Doctor Heiligenstein probably 12 was also. 13 Q. Who is Leigh Thompson? 14 A. Who is he? 15 Q. Yes. 16 A. He's a physician that had 17 served as the -- what was his title, 18 vice-president of medical. 19 Q. Was he the only vice-president 20 of medical while you were responsible for the 21 drug epidemiology unit? 22 A. I don't think so. 23 Q. What other vice-presidents of 24 medical would there have been while you were in Page 242 1 charge of the drug epidemiology unit? 2 A. It seems that -- perhaps Doctor 3 Zerbe, and perhaps Doctor Weinstein and Doctor 4 Reed. 5 Q. They were all -- had the title 6 of vice-president? 7 A. Right. 8 Q. Vice-presidents of Eli Lilly 9 and Company or Lilly Resarch Labs? 10 A. It seems to me that the title 11 was vice-president dash Lilly Research 12 Laboratories, but I'm not sure I had seen their 13 business cards. 14 Q. Did you in any manner report to 15 any of these vice-presidents that you just 16 mentioned? 17 A. Report, I reported to Doctor 18 Talbott. 19 Q. I understand that, but did you 20 have occasion to be involved in meetings in 21 connection with Fluoxetine Hydrochloride where 22 any of these vice-presidents were present? 23 A. Possibly, we have a lot of 24 meetings and a lot of discussions. Page 243 1 Q. Tell me about those that you 2 recall. 3 A. Meetings? 4 Q. Yes, in which one of these 5 vice-presidents of Lilly Research Labs was 6 present. 7 MR. MYERS: Where you discussed 8 Fluoxetine? 9 MR. SMITH: Yes. 10 MR. MYERS: I object to the form, 11 that's an awfully broad question. I mean tell 12 him what you know or recall. 13 A. All I can say is I probably was 14 having four to six hours of meetings every day, 15 and for me to recall specific meetings that I 16 had, I would have a hard time trying to remember. 17 Q. I'm just asking you to remember 18 those that you can. I'm not asking you to 19 remember all of them or a specific one on a 20 specific occasion, I just want to know if you 21 recall any specifics of any particular meeting in 22 connection with Fluoxetine Hydrochloride when any 23 of these vice-presidents of Lilly Research Labs 24 was present? Page 244 1 A. I remember meetings occurring 2 where data would be presented that discussed a 3 number of products, including Fluoxetine. 4 Q. Do you recall being present in 5 a meeting with any of these four vice-presidents 6 that you discussed in which the issue of 7 suicidality in connection with Fluoxetine 8 Hydrochloride was discussed in any manner? 9 A. It seems to me that did come up 10 in some of the meetings as data was presented on 11 Fluoxetine. 12 Q. Can you give me some specifics 13 with respect to when that -- what your 14 recollection is of what that first meeting might 15 have been? 16 A. I couldn't tell you when the 17 first meeting might have been on it. 18 Q. Can you tell me generally what 19 the subject of the discussion was in connection 20 with that first meeting? 21 A. The only way I can answer that 22 is to say that I do remember, again, meetings 23 that occurred where data would be presented on a 24 variety of the products, Fluoxetine included, and Page 245 1 some of the adverse events were discussed about 2 Fluoxetine. And there was always interest on the 3 part of the physicians about incidents and, I 4 guess, severity or whatever the other medical 5 terms that might be applied to it. 6 Q. In connection with suicide and 7 Prozac? 8 A. It seems to me that was one of 9 the ones that was also brought up. I don't 10 remember being in one where we just discussed 11 suicidal ideation, no. 12 Q. But you know that there were 13 meetings where vice-presidents were present where 14 the issue of Fluoxetine and suicidal ideation was 15 discussed? 16 A. Say the question again, I knew 17 there were meetings that that occurred? 18 Q. And you were present at the 19 meetings. 20 A. Yes, that was brought up. 21 Q. And would these meetings have 22 gone back as early as 1988 when you became head 23 of the drug epidemiology unit? 24 A. I can't recall because I don't Page 246 1 remember whether that issue came up. The product 2 was just released in 1988, so it seems to me that 3 that did not become an issue until a little later 4 on, so I don't know whether the issue came up in 5 '88 or '89. 6 Q. It would have been either '88 7 or '89, though, wouldn't it, when you first had a 8 meeting concerning the issue of Fluoxetine and 9 suicidal ideation? 10 A. I think it would probably tie 11 more in my mind to the Teicher article, whenever 12 it was published. 13 Q. You recall that there was a 14 concern about this before the Teicher article, 15 don't you? 16 A. No, I don't. 17 Q. You deny that there was concern 18 at Lilly concerning suicidal ideation, suicide 19 attempts, and suicides that had occurred in 20 individuals being treated with Fluoxetine prior 21 to the Teicher article? 22 A. I recall nothing in my 23 knowledge related to suicidal ideation prior to 24 the Teicher article. Page 247 1 Q. What are you saying, it was a 2 concern or you just don't recall there being a 3 concern prior to the Teicher article? 4 A. It was nothing that I was aware 5 of before the Teicher article. 6 Q. Well, by the time the Teicher 7 article came out in February of 1990, you had 8 been in charge of the drug epidemiology unit and 9 responsible for the DEN system since 1988, had 10 you not? 11 A. That's correct. 12 Q. And you had, in your capacity 13 as head of the drug epidemiology unit, and 14 responsible for the DEN system, received records 15 concerning individuals taking Fluoxetine who had 16 committed suicide, had you not? 17 A. Prior to? 18 Q. Prior to February 1989. 19 A. I'm not aware of that, no. 20 Q. You've never noticed it before 21 February of 1990, that there was adverse events 22 describing suicides before February of 1990? 23 A. In my capacity, I am not aware 24 of any of those discussions taking place, nor am Page 248 1 I aware of any of the suicidal ideation things 2 that you stated prior to the Teicher article. 3 Q. Did you review the data that 4 was being generated by this sophisticated 5 computer system between 1988 and February, 1990 6 to get some idea of the type of adverse 7 experiences that were being reported with respect 8 to this drug? 9 A. No. 10 Q. You didn't review it at all? 11 A. Didn't review what? 12 Q. Any of the data concerning the 13 nature of the adverse events that were being 14 experienced with this medication. 15 A. No, that was not part of my 16 responsibility. 17 Q. To review the data that was 18 being generated that was your responsibility -- 19 it was your responsibility to generate the data, 20 wasn't it? 21 A. No, it was not my 22 responsibility to generate data. 23 Q. It was your responsibility to 24 see that the data was collected? Page 249 1 A. Correct, right. 2 Q. And you were responsible for 3 individuals who were finally generating that data 4 concerning the adverse events, weren't you? 5 A. State that -- finally 6 generating? 7 Q. Pumping out 1639s. 8 A. I was responsible for people in 9 the drug epidemiology unit, correct. 10 Q. And they were responsible for 11 complying with federal regulations with respect 12 to when a 1639 should be reported; correct? 13 A. That's correct. 14 Q. So you were responsible for 15 individuals who were collecting and generating 16 data concerning adverse experiences received by 17 Eli Lilly and Company, were you not -- 18 A. Correct. 19 Q. -- with respect to Eli Lilly 20 pharmaceuticals; correct? 21 A. Right, right. 22 Q. But is it your testimony that 23 you never made any kind of review yourself or 24 analysis yourself concerning frequency or nature Page 250 1 of particular adverse events that was experienced 2 by this medication? 3 A. That was not in the realm of my 4 responsibility. 5 Q. Whether it was in the realm of 6 your responsibilities, did you ever make any type 7 of review of this type of data to have any idea 8 of what kind of adverse experiences were being 9 reported with this medication? 10 A. I don't recall that I ever did 11 that, no. 12 Q. Did you do it after February of 13 1990? 14 A. No. 15 Q. Who did? 16 A. The responsibility for that 17 would be with the research physician. 18 Q. Are you talking about Doctors 19 Jamie Street, David Wheadon, Doctor Beasley, 20 Doctor Goldstein, Doctor Kotsanos and Doctor 21 Heiligenstein? 22 A. The medical people, correct. 23 Q. Do you know of any other 24 medical people that were reviewing adverse events Page 251 1 in connection with Fluoxetine? 2 MR. MYERS: When you say medical 3 people, you mean physicians? 4 Q. Whatever he means by medical 5 people, he used the term. 6 A. The responsibility for 7 reviewing the reports lied with the person who 8 would see it in the DEU, and then they would work 9 with that research physician. Obviously with any 10 product, if there were any new, unique adverse 11 events that were occurring because of our 12 concensus orientation organization, there would 13 be a lot of discussions with medical people, 14 depending on whatever the event was. 15 Q. Did you participate in any of 16 those discussions? 17 A. I attended some meetings, yes. 18 Q. Did you listen at those 19 meetings? 20 A. Sure. 21 Q. Did you hear the issue of 22 suicidality with respect to Fluoxetine come up as 23 an issue being raised by reported events in 24 connection with this medication? Page 252 1 A. Yes, I was in meetings where I 2 heard suicidal ideation brought up as an issue, 3 yes. 4 Q. What were those discussions 5 about? 6 A. Those discussions would have 7 been about frequency, they would have had to do 8 with whatever information that was provided on 9 the reports that would help to give an 10 understanding of them. 11 Q. You mean sufficiency of the 12 information that was being reported? 13 A. That would be one question that 14 would be brought up. 15 Q. What else? 16 A. And understanding the reports. 17 Q. What do you mean understanding 18 the reports? 19 A. From a medical standpoint. 20 Q. Was there something difficult 21 about the records that was causing confusion with 22 respect to how they should be understood? 23 Q. As I understand it, there's 24 always a question about whether things are Page 253 1 related to a drug or whether they're related to 2 an illness, but those are all medical questions, 3 and for me to interpose my judgment on that would 4 not -- I mean I really had no input on that. 5 Q. And I'm not asking you for your 6 medical judgment or your input on that, I'm 7 asking you the subject of the discussion 8 concerning suicidality and Fluoxetine, and how it 9 was raised in -- was there some connection with 10 respect to understanding, being able to 11 understand the information that you had 12 concerning a particular report of suicide, 13 suicidal ideation or suicide attempts? 14 A. I don't understand that 15 question at all. 16 Q. You said there was discussions 17 concerning understanding the events. 18 A. Right. 19 Q. Was it the understanding of the 20 information that you had collected concerning the 21 event? 22 A. That could be one of the 23 questions that someone would raise or ask to have 24 confirmed. Page 254 1 Q. Was there an issue about the 2 sufficiency of the information that had been 3 collected by the drug epidemiology unit? 4 A. I don't recall that, no. 5 Q. Was there a concern about the 6 sufficiency of any information that had been put 7 in the Drug Experience Network? 8 A. I don't recall that either. 9 Q. Okay. What was the confusion 10 about understanding the information that you had? 11 MR. MYERS: Hold on. You used the word 12 confusion, he used the word understanding, you 13 now coupled them so I object to the form. 14 Q. What was the problem with 15 having -- or what was the discussion concerning 16 understanding the nature of the information 17 concerning the events of suicide, suicidal 18 ideation or suicide attempts? 19 A. First off, I do not recall 20 there being any confusion, I remember people 21 asking questions as they do in our company to 22 confirm that what a physician is doing, other 23 physicians would ask questions to assure that 24 everyone understood where the physician was Page 255 1 coming from based upon what premise of 2 information and so on. So it was really more of 3 an intellectual discussion so that everyone had a 4 full understanding of the data and what the data 5 meant. 6 Q. Was there a discussion 7 concerning whether or not there was sufficient 8 information being obtained by the drug 9 epidemiology unit and through the DEN system in 10 order to make some type of determination 11 concerning the relationship between suicide and 12 Fluoxetine? 13 A. I don't recall there ever being 14 a question of insufficient information. I will 15 say that if there were questions about needing 16 more information, we would make calls, we also 17 had people going out and picking up information. 18 So whenever the question came out about do we 19 need more information, that was pursued in a 20 diligent fashion. 21 Q. You say people were making 22 calls. 23 A. Right. 24 Q. To get more information. Page 256 1 A. Uh-huh. 2 Q. Give me some explanation of 3 that. 4 A. Well, a clinical research 5 administrator or a physician might call the 6 health care practitioner who provided the report 7 and gather more information. 8 Q. All right. You say also that 9 they were going out and picking up information. 10 A. Right. 11 Q. What kind of information would 12 be picked up? 13 A. I don't remember what all that 14 information might be, but I do recall generally 15 speaking that we would pick up things like 16 autopsy reports, maybe charts or graph 17 information that couldn't be communicated in a 18 phone call. So there were times that that 19 information was picked up that way. 20 Q. Because the physicians, as far 21 as what you observed, felt like autopsy results 22 would be beneficial in understanding the 23 relationship between Fluoxetine and suicide? 24 A. I didn't say Fluoxetine and Page 257 1 suicide, I said I do remember in reports there 2 were times that we would go out and gather that 3 kind of information. 4 Q. Because that information was 5 felt by the physicians to be necessary to make 6 further inquiry into this issue? 7 A. That's right, in order for them 8 to come to a better medical understanding of what 9 was occurring. 10 Q. Were you present in any of 11 these meetings when outside consultants were 12 called in to discuss this issue? 13 A. I don't remember that I was, 14 no. 15 Q. Do you recall being in any of 16 these meetings or having any knowledge at these 17 meetings where outside statisticians were being 18 called in to review this data? 19 A. No. 20 Q. You mentioned that there was a 21 frequency issue that was discussed in connection 22 with these meetings -- 23 A. Uh-huh. 24 Q. -- where Fluoxetine and Page 258 1 suicidality would be discussed. I assume the 2 question arose as to how frequently are we being 3 made aware that this phenomena is being reported 4 by individuals taking this drug. 5 A. Generally that would seem to be 6 something that I can recall, yes. 7 Q. What are the regulations, 8 requirements, with respect to frequency of a 9 particular adverse event, and whether or not that 10 needs to be reported to the Food and Drug 11 Administration? 12 A. One regulation that I recall 13 indicates that if you have a serious expected 14 reports that increase in frequency, at the time 15 that you become aware of that, then you provide a 16 fifteen-day report to the FDA. 17 Q. What's the number of increase 18 in frequency, over what period of time that it's 19 used? 20 A. It seems to me there were 21 several algorithms that were used, some were 22 quarter to quarter, some year to year, some on 23 just an ad hoc basis, if there was a feeling that 24 that needed to be looked at. But I can't give Page 259 1 you the specifics on that. 2 MR. SMITH: That's all I have. 3 MS. ZETTLER: Can we take a quick 4 break? 5 MR. MYERS: Sure. 6 (A SHORT RECESS WAS TAKEN.) 7 * * * * * * * * * * 8 CROSS EXAMINATION 9 BY MS. ZETTLER: 10 Q. Mister Noone, I don't think we 11 met formally yesterday. My name is Nancy 12 Zettler, and I represent a group of plaintiffs in 13 the Fentress versus Shea Communications case down 14 in Kentucky. 15 MR. MYERS: The Wesbecker case. 16 Q. The Wesbecker case. 17 A. Oh, okay. 18 Q. When you were talking to Paul 19 before the break, you testified that if an 20 increased frequency of expected events occurs, 21 then it would be investigated, correct, an 22 increase in frequency? 23 A. No, I think what I said was if 24 it was serious and expected, and there had been Page 260 1 an increase in frequency, there is a regulation 2 that applies to that and that generates a report. 3 Q. When you say that generates a 4 report, you mean the computer generates a report 5 or you generate a report in response to the 6 regulation? 7 A. Both. 8 Q. The computer automatically 9 generates a report? 10 A. At certain prescribed 11 intervals, yes. 12 Q. What are those prescribed 13 intervals? 14 A. With products that are on the 15 market less than three years, it would be at 16 quarterly intervals, products on the market 17 longer than three years, it would be at annual 18 intervals. And that's from the computer end of 19 it. And there were other ad hoc ones that were 20 done in between those intervals as medical 21 judgment would dictate. 22 Q. So with post-marketing adverse 23 event reports we have three intervals, one is 24 quarterly if it's a drug that's been on the Page 261 1 market less than three years, annually if it's a 2 drug that's been on the market more than three 3 years, and intervals that are determined by seven 4 clinical research physicians at Lilly in the 5 interim? 6 A. Yes, or anyone else that might 7 suggest that we need to take a look at that. 8 Q. Okay. Is there a minimum 9 number of adverse events that had to be reported 10 before the computer will kick out a report on 11 increased adverse events? 12 A. I don't remember what that 13 number is. 14 Q. I believe you testified in your 15 last deposition that it was fifteen, does this 16 that refresh your recollection? 17 MR. MYERS: Where did he say that 18 because I don't -- 19 A. I don't recall seeing that. 20 MR. MYERS: Nancy, look on -- I see the 21 number fifteen on page -- start on page two 22 eleven and go through page two thirteen and see 23 if that's what you're talking about. I don't 24 think that's the same thing, but I don't know. Page 262 1 MS. ZETTLER: Okay. I have an 2 abstract. An adverse reaction occurs fifteen 3 times, some discussion would occur about whether 4 the particular adverse reaction should be put in 5 the package literature. I stand corrected. 6 (DISCUSSION OFF THE RECORD.) 7 Q. Do you recall what number it 8 would be? 9 A. I can't completely remember 10 that, it seemed to me this was a fairly small 11 number. 12 Q. Less than a hundred? 13 A. Oh, yes, definitely. 14 Q. Less than fifty? 15 A. You're talking about going from 16 one quarter to the next? 17 Q. That's what I'm trying to find 18 out. What would happen -- is it a quarterly 19 thing, would it have to be increased -- 20 A. Yes -- 21 Q. Let me finish my question. 22 Would it have to be an increase in the number of 23 events per quarter or since the drug was 24 marketed? In other words say you have suicides Page 263 1 that occur from, I guess, it's January of '88 2 when the drug was marketed, when Prozac was 3 marketed, and say you have two suicides that 4 occur the first quarter and then it goes up to 5 twenty. Is that enough to initiate an increased 6 adverse event report? 7 MR. MYERS: Are you asking him over 8 what period of time do you measure the increase? 9 MS. ZETTLER: I think he understood my 10 question. 11 Q. Did you understand my question? 12 A. If you're saying that it goes 13 from two up to twenty in a quarter, from one 14 quarter to the next, would that be reported as 15 increased frequency. 16 Q. Right. 17 A. The answer to that would be 18 what is the denominator. So if you had a hundred 19 patients, two over a hundred patients that were 20 treated or whatever denominator you were using, 21 and then you went to twenty and your denominator 22 also went ten-fold, that would not be an 23 increased frequency. 24 Q. So it's a percentage? Page 264 1 A. Right. 2 Q. Percentage of total people that 3 the drug had been marketed? 4 A. I don't remember what the 5 algorithm was, it may have related to units sold. 6 It probably had to do with more units sold 7 because it would be difficult to understand what 8 total number of patients were actually on the 9 drug. 10 Q. There's no way of determining 11 the total number of patients on the drug? 12 A. Not that I'm aware of. 13 Q. Does that mean you can write 14 prescriptions but it doesn't necessarily mean 15 that people are on the drug? 16 A. It can be because the number of 17 pills that are given to a patient are large or 18 they may be small, there's -- and it's difficult 19 to just track that because we don't sell directly 20 to the patient, it's just sold to the wholesaler, 21 and then -- 22 Q. Just because you sell it to the 23 wholesaler doesn's mean it actually eventually 24 makes it to a patient? Page 265 1 A. That's correct. 2 Q. I've seen various documents 3 over the past year that talk about estimates of 4 people who have been prescribed Prozac. How do 5 you guys come up with those estimates, generally? 6 A. I'm not sure how they come up 7 with those, I've never sat in on sessions where 8 they developed that, those numbers. 9 Q. Okay. Is it your understanding 10 that there is a requirement by the FDA and/or the 11 DEA that prescriptions for drugs are monitored, 12 in other words kept tract of by, say, 13 pharmacists, doctors, drug companies, et cetera? 14 A. I'm not sure I follow that 15 question, I'm not aware of what you're referring 16 to when you say it's monitored. 17 Q. How about drug accountability, 18 are you aware of what drug accountability is? 19 A. I'm not sure of the specifics 20 of that, I would assume that would just mean that 21 we know who we sell it to, the first person that 22 receives it whether it is being the wholesaler. 23 Q. Did any of your 24 responsibilities in the regulatory department at Page 266 1 Lilly include keeping track of the numbers of 2 prescriptions written for Prozac or any other 3 drug prescriptions, drugs manufactured by Lilly? 4 A. No. 5 Q. So this increase in frequency 6 is done on a percentage basis as opposed to 7 purely a numerical basis? 8 A. That's correct. As I recall, 9 the denominator was based upon units that we 10 sold. 11 Q. Are these reports generated as 12 part of the DEN system, the computer reports? 13 A. Those that are generated on the 14 quarterly and annual system would be, annual 15 basis would be. 16 Q. So information on units sold 17 would have to be entered into the data base 18 somehow? 19 A. That's correct. 20 Q. Who would do that? 21 A. I'm not sure who did that, I 22 remember that we got that information from the 23 manufacturing or distribution area in terms of 24 the number of units that went out the door. Page 267 1 Q. Let's talk about the discussion 2 in the former deposition about the number of 3 events that would have to occur before a 4 consideration was made including it in the 5 package insert. Do you recall that number being 6 around fifteen? 7 A. No, I don't recall what my 8 comments were at that time, but it would -- I 9 think it would relate, and again, you have to 10 realize that I never really had any 11 responsibility for putting anything into a 12 package literature, but certainly in my mind it 13 would relate to the severity of the issue, would 14 be one reason, and your understanding of it as 15 well. 16 Q. Severity of the adverse event 17 you mean? 18 A. Right. 19 Q. Is that -- when you say 20 severity, are you talking again about the FDA 21 definition of serious and unexpected? 22 A. That would have a piece of play 23 in it, yes. 24 Q. Any other definitions of Page 268 1 serious that were taken into consideration? 2 A. No, but from a medical 3 standpoint, that if you had granulocytosis 4 occurring, but less frequently, versus a mild 5 rash, the granulocytosis would probably get into 6 the literature more quickly if you thought it was 7 attributed to the drug. 8 Q. Did Lilly consider at any time 9 suicidality or suicide a serious adverse event? 10 MR. MYERS: When you say serious, under 11 the regs, would it be captured as such? 12 MS. ZETTLER: Serious under his 13 definition that he's talking about right now with 14 regards to including it in a package insert. 15 A. I didn't sit in on any of those 16 meetings. If someone is committing suicide, then 17 that in my mind is a serious issue. 18 Q. What about suicidal ideation, 19 have you thought of that? 20 A. I suspect that it would be. 21 Q. So in your opinion suicidal 22 ideation and suicide is a serious issue? 23 A. It is a serious issue, yes. 24 Q. Is it a serious issue as Page 269 1 defined by Lilly with regards to inclusion in the 2 package insert? 3 A. I'm not sure, run the question 4 by me again because my mind -- that question is 5 going several different directions, and I'm not 6 sure I understand. 7 Q. We just talked about including 8 adverse events in the package insert; correct? 9 A. Right. 10 Q. And the criteria for at least 11 consideration in including an individual adverse 12 event in the package insert was the seriousness 13 of the adverse event; correct? 14 A. Uh-huh. 15 MR. MYERS: Yes. 16 A. Yes, I'm sorry. 17 Q. At any time, to your knowledge, 18 has Lilly considered suicidal ideation or actual 19 suicide, suicide attempts, serious under the 20 criteria used for consideration and inclusion in 21 the package insert? 22 A. I'm sure that it must have 23 been. You're looking at the seriousness of the 24 event and you're also looking at how it relates Page 270 1 to the drug itself. 2 Q. And the determination on how it 3 relates to the drug itself is made by clinical 4 research physicians at Lilly, right? 5 A. Yes. 6 Q. Are you familiar with a man 7 named Claude Bouchy, have you ever heard that 8 name before? 9 A. I've heard the name, yes, but I 10 can't remember where that came from. 11 Q. Are you aware that Doctor 12 Bouchy took exception with the adverse event 13 terminology assignments made by Lilly with 14 regards to Prozac at some point in time? 15 A. No, I'm not. 16 Q. Are you aware of any other 17 employee at Lilly that took exception with the 18 way adverse event terms were assigned by Lilly 19 with regard to Prozac adverse events? 20 A. I'm not aware of that, no. 21 Q. Are you aware that at one time 22 it was Lilly's policy to assign the term overdose 23 to intentional overdose as well as accidental 24 overdose? Page 271 1 A. Apply the term? 2 Q. Right. 3 A. It seems to me I recall 4 something like that, yes. 5 Q. Did you ever have a problem 6 with that? 7 A. I don't recall that I had a 8 problem with it, no. 9 Q. Did you ever have a problem 10 with Lilly assigning the term depression to 11 suicidal ideation? 12 A. I guess I couldn't tell you 13 whether that was applied to that or not. 14 Q. So you don't remember whether 15 or not the term depression was assigned to an 16 adverse event indicating suicidal ideation on 17 Fluoxetine? 18 MR. MYERS: Via some event dictionary. 19 MS. ZETTLER: Right, by Lilly. 20 A. Repeat the question again, 21 please. 22 Q. Sure. Are you aware that it 23 was, at least at some point in time, policy at 24 Lilly to assign the term depression to the Page 272 1 adverse event of suicidal ideation? 2 MR. MYERS: I object to the form, that 3 assumes facts that are not in evidence. If you 4 know, tell her. 5 A. I'm not aware of that, no. 6 Q. Would you have a problem with 7 that if that was a fact, if that was the case? 8 A. I'm not a medical person, I 9 don't know the rationale behind that if indeed 10 that was done. 11 Q. Are you aware that it's Lilly's 12 position that suicidal ideation is generally just 13 a result of the underlying disease of depression 14 and not a result of these Fluoxetine -- the use 15 of Fluoxetine? 16 A. I have heard that, yes. 17 Q. Do you take exception with 18 that? 19 A. No. 20 Q. Do you agree with that? 21 A. I'm not a medical person, but I 22 have never seen anything that would indicate that 23 it was other than that. 24 Q. What would happen with the Page 273 1 quarterly or yearly increased frequency reports 2 generated by Lilly, physically what would happen 3 with them? 4 A. What would happen with the 5 reports that are generated on a quarterly or 6 annual basis, I'm not sure where they were. The 7 information is reviewed, and I'm not sure whether 8 we kept the paper output or we just had it as a 9 part of our electronic data, I really can't 10 remember. 11 Q. Who reviewed it? 12 A. Research physician, drug 13 epidemiology unit people. 14 Q. Did you ever review the 15 quarterly reports? 16 A. No. 17 Q. Why not? 18 A. It was not in my immediate 19 amount -- or area of responsibility, I'm not a 20 technical person, so it wouldn't have -- it 21 wouldn't have been -- it wouldn't have been of 22 any value. 23 Q. Whose responsibility was it to 24 make sure that all adverse events fitting the FDA Page 274 1 criteria or Lilly criteria were actually entered 2 into the DEN data base? 3 A. Well, it's a joint 4 responsibility, and it goes -- the only way I can 5 answer that is go back to the point that whoever 6 learns of the information, has the 7 responsibilities to report it to the drug 8 epidemiology unit. And then once it's reported 9 there, it's put into the Drug Experience Network, 10 and then the algorithm will drive the report to 11 the agency. 12 Q. Is this -- when you say that 13 the report, the algorithm would drive the report 14 to the agency, is this something that's 15 automatically reported to the FDA via computer? 16 A. No. 17 Q. So it's something that has to 18 be reviewed and generated in paper form for 19 submission to the FDA by Lilly personnel? 20 A. The information is put in or 21 was put into DEN, and then the reports are 22 generated in the form of 1639s or CIOMS reports, 23 if they qualify for the fifteen days, every 24 Monday, and then they were mailed on Tuesday to Page 275 1 meet the time frame. 2 Q. What about the quarterly 3 increased frequency or the annual increased 4 frequency reports? 5 A. That information was generated 6 in a timely fashion on a quarterly basis, and it 7 was intended that whatever would be kicked out, 8 there was a timetable set up that you -- once it 9 was reviewed, then it was submitted to the FDA in 10 fifteen days if indeed you did have an increased 11 frequency. 12 Q. In what form, I mean is there 13 an FDA form that you have to fill out? 14 A. No, it's not a 1639, as I 15 recall it was -- seems like it was more of a 16 narrative report, but I don't remember now what 17 that looked like. 18 Q. Who generated that report? 19 A. The information would be 20 reviewed by the CRA and the physician, and then 21 they would jointly put the information in the 22 appropriate format -- or not format, but whatever 23 they felt made sense that would depict what the 24 issue was and send it in. Page 276 1 Q. What would be your 2 responsibility specifically with regards to the 3 generation of those reports? 4 A. What was my responsibility? 5 Q. Right. 6 A. I basically did not have any 7 specific responsibility with that. 8 Q. What were your responsibilities 9 as manager of the DEU? 10 A. It was with the recruitment of 11 personnel into the area to help assure that we 12 had the appropriate training there in the area. 13 Also to interface with other folks in the 14 division so that the team approach was 15 solidified. And again, as I indicated yesterday, 16 that was just one of the areas that I worked 17 with. 18 Q. What other areas did you work 19 with? 20 A. The international product 21 registration area, the regulatory services area, 22 the medical laboratory services group, reprints. 23 Q. Who had responsibility in the 24 DEU to make sure everybody was doing their job? Page 277 1 A. Basically I was the one who did 2 the performance appraisals on the CRAs that were 3 in the unit. 4 Q. How would you rate people's 5 performances if you weren't monitoring what they 6 were doing? 7 A. Well, I had a lot of meetings 8 with staff, also I collected input from 9 physicians about their performance as well. 10 Q. On a day-to-day basis, who 11 would check on these people to make sure they 12 were in fact entering information into the DEN in 13 a proper manner? 14 A. Well, first off, it's not -- we 15 didn't feel it was necessary to ride shotgun on 16 people, so to speak. We recruited very well 17 qualified, well trained people coming into the 18 unit to begin with, most of them were nurses and 19 registered pharmacists, and most had had previous 20 success assignments before they came into the 21 unit. 22 Q. So basically what you're saying 23 is they were fairly autonomous in their duties? 24 A. Autonomous in some respects, Page 278 1 but in order to effect or get the job done, they 2 had to collaborate with physicians. 3 Q. And the physicians had the 4 ultimate say as to how they did their job as far 5 as what would be entered into the DEN and things 6 of that nature? 7 MR. MYERS: I object to the form, 8 that's not what he said. 9 MS. ZETTLER: I'm asking him. 10 A. No, we did not. 11 Q. So who would make that 12 decision? 13 A. Who would make what decision? 14 Q. Say a specific adverse event 15 came in, whose decision -- and there was a 16 question whether or not it should be entered into 17 the DEN for whatever reason, who would have the 18 ultimate decision as to whether or not 19 information on that adverse event would be 20 entered into the DEN? 21 A. The rule was all information 22 that related to those qualified reports had to be 23 put into DEN. 24 Q. Who made the decision as to Page 279 1 which reports would qualify? 2 A. All the reports that came into 3 the unit were in the categories we discussed 4 before that were spontaneous, all of those were 5 put into the system. 6 Q. How about with regards to the 7 clinical trial adverse events, you testified 8 earlier that only those events that were serious 9 would be entered into the DEN, right? 10 A. That's correct. 11 Q. Who made that decisions as to 12 whether or not clinical trial adverse events 13 qualified for entering into the DEN? 14 A. If the report involved 15 hospitalization or any other serious criteria, it 16 had to be put into the DEN. 17 Q. Seriousness of an adverse event 18 is outcome related; correct? 19 A. That's correct. 20 Q. So you may have somebody 21 theoretically who makes a suicide attempt, but if 22 they don't fit under one of these criteria as set 23 out by the FDA, it's not considered serious, 24 right? Page 280 1 A. Hypothetically. 2 Q. How about with the clinical 3 trial adverse events, there is a frequency report 4 generated similar to the spontaneous adverse 5 event? 6 A. I can't remember what the -- I 7 can't remember what our -- what the application 8 was on that. I'm not -- I don't remember what 9 the regulation -- it seems to me that the NDA 10 regulation was the one that drove the increased 11 frequency algorithm. 12 Q. How would you measure increased 13 frequency of a particular adverse event within a 14 clinical trial process? 15 A. If it applied and if it were 16 serious, then the algorithm would be the same as 17 what it is with other serious expected reports. 18 Q. What do you mean when you say 19 if it applied? 20 A. I don't recall whether it did 21 apply, I can't recall that. 22 Q. Whether what applied? 23 A. Whether the increased frequency 24 algorithm applied to clinical trial reports or Page 281 1 not. 2 Q. How would we find that out, 3 whether or not it applied? 4 A. We could probably check with 5 the regulation, I suspect would be one way to 6 look at it. 7 Q. If it didn't apply, and the 8 regulation didn't require that an increased 9 frequency report be generated with regards to 10 clinical trial adverse events, how would you 11 track an increase frequency at Lilly, physically, 12 how would it be done? 13 A. Say that again. 14 Q. Sure. If the requirement that 15 a quarterly or annual increased adverse event 16 report be generated did not apply to clinical 17 trial adverse events, how at Lilly would the 18 increase of the adverse events be tracked, 19 physically? 20 A. If it did -- 21 Q. If it did not apply. 22 A. If it did not apply to 23 regulation, and if it was not a regulatory 24 requirement, then I would -- I wouldn't know that Page 282 1 we had an algorithm to deal with that. But I 2 can't recall what the algorithm, frankly, as I 3 said before, that we had that applied to the 4 clinical trial on frequency. 5 Q. So number one, you don't know 6 whether or not a determination of increased 7 frequency in clinical trials was done. 8 A. Yes, I can't recall that, 9 correct. 10 Q. And number two, if it was, you 11 don't remember in what manner it was done in? 12 A. That's correct, yes. 13 Q. On the quarterly and yearly 14 reports that are generated by the computer on 15 increased frequency, how is that done, in other 16 words, say, for suicide attempts or suicide, 17 would the computer kick out a line listing say 18 suicide attempts to date, so many, or percentage 19 or whatever, in other words is it event term 20 specific? 21 A. As I recall, it was. But you 22 have to understand, I did not review those 23 reports individually. I can see in my mind 24 different events that we had that we looked at. Page 283 1 Q. What events? 2 A. Oh, I can talk rash and 3 verticaria and things like that. 4 Q. How is it that you can remember 5 reviewing those adverse events, but you can't 6 remember reviewing adverse events related to 7 suicidality? 8 A. Well, because those terms -- 9 rash, for one, is a much more common adverse 10 event that occurs across a broad range of 11 products. 12 Q. Who is Gordon Gilad, G-I-L-A-D? 13 A. He was a research physician 14 that worked for Lilly. 15 Q. Is he still at Lilly? 16 A. I don't know. I know he moved 17 to Europe -- I think he did leave, but I lost 18 track of him. 19 Q. Where was he the last time you 20 knew where he was? 21 A. I think he was in the UK 22 someplace. 23 Q. Either at Erl Wood or 24 Basingstoke? Page 284 1 A. I think that's correct. 2 Q. Do you remember if it was Erl 3 Wood as opposed to Basingstoke or vice versa? 4 A. I don't remember, if I had to 5 guess I would say Erl Wood. 6 Q. Is it your understanding that 7 at some period of time, at least while you were 8 working in the DEU, that Doctor Gilad was charged 9 with monitoring adverse events with regards to 10 Fluoxetine? 11 A. I don't remember that, no. 12 Q. Was there any specific clinical 13 research physician that was charged with that 14 duty, to your knowledge, while you were at the 15 DEU? 16 A. Not to my knowledge. 17 Q. Earlier I think when you were 18 talking with Paul, you said that Doctor Thompson, 19 Leigh Thompson, had been a vice-president of 20 medical? 21 A. Right. 22 Q. Is he no longer in that 23 position? 24 A. No, he is not. Page 285 1 Q. Where is he now? 2 A. He's called something like 3 chief scientific officer. 4 Q. He's still at Lilly? 5 A. Yes. 6 Q. How has his duties, if you 7 know, changed from when he was a vice-president 8 of medical? 9 A. I'm not that familiar with his 10 current duties, but at this point he does not 11 have responsibility for the medical division. 12 Q. He does not? 13 A. Does not, that's correct. 14 Q. When did he change positions? 15 A. Sometime in the last -- 16 sometime in the last year. 17 Q. Do you know if that's a 18 promotion? 19 A. I don't know what his salary 20 level is, he was reporting directly to the 21 chairman of the board, I know, when he went into 22 this assignment. 23 Q. Have you ever heard of a person 24 named Patricia Williams? Page 286 1 A. Patricia Williams, that doesn't 2 ring a bell. 3 Q. How about Dorothy Dobbs? 4 A. Yes. 5 Q. Who is Dorothy Dobbs? 6 A. Dorothy Dobbs was a -- I think 7 we called them regulatory scientists or something 8 like that. I remember her back in the early to 9 mid-'80s. 10 Q. Do you know what she did in 11 regulatory? 12 A. It seems to me at that time we 13 had three or four people that were working with 14 different therapeutic groups and working the 15 products in those different groups from a 16 regulatory standpoint. 17 Q. Do you know where Doctor Dobbs 18 is now -- she's an M.D., right? 19 A. I think that's right, but I 20 couldn't tell you. 21 Q. Do you know where she is now? 22 A. No, I don't. 23 Q. Does she still work for Lilly? 24 A. No, she does not work for Page 287 1 Lilly. 2 Q. Do you know when she left 3 Lilly? 4 A. Sometime in the middle '80s, I 5 think. 6 Q. Do you know why she left Lilly? 7 A. No. 8 Q. Do you know if she went to work 9 for another drug company? 10 A. No, I don't. 11 Q. Yesterday when you were talking 12 with Paul, you said there had been at least three 13 revisions of DEN, is that true? 14 MR. MYERS: No, three reorganizations 15 of the DEU. 16 Q. Three reorganizations of DEU, 17 okay. To your knowledge, have there ever been 18 any revisions of the DEN system while you were 19 working in the DEU or after or before? 20 A. Were there any revisions to the 21 DEN -- yes. 22 Q. How many times has that system 23 been revised to your knowledge? 24 A. It seems to me there were Page 288 1 ongoing kinds of enhancements that took place, 2 but we moved at one point from what we called DEN 3 one to DEN two. That was the most significant 4 thing that occurred. 5 Q. What was the most significant 6 thing between DEN one and DEN two? 7 A. In DEN two, people who were in 8 international affiliates could now input their 9 information directly into DEN, whereas before 10 they had to send a fax or whatever information to 11 the drug epidemiology unit staff, and then it had 12 to be entered. 13 Q. When did that change take 14 place? 15 A. It seems like it was sometime 16 in '89. 17 Q. Do you know why it was done? 18 A. To enhance the system, give 19 greater access to the affiliate personnel. They 20 now could not only input, but now they could go 21 in and look at the system as well, and they could 22 then deal with their own local regulatory 23 authorities based upon questions that they might 24 be asked by their own regulatory authorities. Page 289 1 Q. Was there a particular need 2 that was being addressed by the change? 3 A. Customer orientation more than 4 anything else. 5 Q. Did it have anything to do with 6 increased adverse event reporting? 7 A. Not that I recall, because -- 8 and the reason I say that was that that plan had 9 started long before we had increased numbers of 10 adverse events. 11 Q. The plan to change the DEN 12 started before that? 13 A. To continue to enhance it, 14 right. 15 Q. When did the plan start? 16 A. I couldn't tell you when that 17 was, I remember discussions occurring about that 18 even -- well, it seems to me even before I went 19 into the drug epidemiology unit group. 20 Q. You were a detail man before, 21 right? 22 A. Correct. 23 Q. Were discussions going on at 24 that time when you were a detail man about Page 290 1 changing the DEN system? 2 A. I don't think the DEN system 3 existed at the time I was a detail person. 4 Q. Are you aware of a situation 5 where information from the DEN was transferred to 6 the host computer? 7 A. Information from DEN 8 transferred to the host computer. It seems like 9 I heard something about that, but I couldn't tell 10 you what that was. 11 (PLAINTIFFS' EXHIBIT NO. 2 WAS 12 MARKED FOR IDENTIFICATION AND 13 RECEIVED IN EVIDENCE.) 14 Q. Mister Noone, have you had a 15 chance to look at Exhibit 2? 16 A. Yes. 17 Q. Have you seen this exhibit 18 before or any part of this exhibit before? 19 A. I may have, but I certainly 20 don't -- it doesn't seem to ring a bell, no. 21 Q. Do you have any idea why this 22 would be produced as part of your personal files 23 from Eli Lilly? 24 A. No. Page 291 1 Q. On the first page it talks 2 about frequency tables of NDA submissions to the 3 FDA; correct? 4 A. That's what the statement says, 5 yes. 6 Q. Underneath that it says the 7 tables include both trials, spontaneous reports 8 and reports of both U.S. and non-U.S. origin; 9 correct? 10 A. Right. 11 Q. Under that it says tables do 12 not include submissions made on reports that were 13 later deleted from a DEN data base. Do you know 14 what they mean by reports that were later deleted 15 from a DEN data base? 16 A. I would assume that would mean 17 the duplicate reports. 18 Q. After that it says the DEN 19 coordinator has records of these reports and 20 corresponding submissions, right? 21 A. Right. 22 Q. You were in the DEN in '91, 23 right? 24 A. I'm sorry? Page 292 1 Q. You were working in the DEN -- 2 or DEU in '91? 3 A. I was the -- let me think a 4 second. That close -- I don't remember when it 5 was that I did move on to the other area, but I 6 think I was there then, yes. 7 Q. Who replaced you in that 8 position when you left the DEU? 9 A. Earlene Ashbrook became the 10 manager for the drug epidemiology unit. 11 Q. Who was the DEN coordinator in 12 early 1991? 13 A. That should have been -- that 14 was either Pam Hadley or Brenda Roach. 15 Q. Is it your recollection that 16 there were a lot of duplicate reports that were 17 entered into the DEN on adverse events? 18 A. Define a lot. 19 Q. More than ten percent? 20 A. No. 21 Q. More than fifteen percent? 22 A. No. 23 Q. More than one percent? 24 A. I doubt it. Page 293 1 Q. On the top of the first page it 2 says DEN special request log sixty-seven. What 3 does that mean? 4 A. I don't remember what that 5 would have meant, I don't know whether that's 6 usher's request or whether that's the number 7 that's processed by Pamela Johnson. 8 Q. Have you ever heard of a DEN 9 special request? 10 A. I could not apply a definition 11 to that, no. 12 Q. Have you ever made a DEN 13 special request? 14 A. Not that I can recall. 15 MR. SMITH: Would somebody have to have 16 authority to make a special request? 17 THE WITNESS: Would someone have to 18 have authority to do that. Generally I would say 19 that's true, yes. 20 Q. Is there specific people that 21 were allowed to work in the DEN system or was 22 that generally any employee could work in the DEN 23 system? 24 MR. MYERS: When you say work in the Page 294 1 DEN system, do you mean entering in the DEU? 2 Q. Could any employ at Lilly 3 working on Prozac or Fluoxetine get into the DEN 4 system and either enter or delete or review 5 information? 6 A. No, there were different levels 7 of access, and in terms of who could enter and 8 who could read and so on. 9 Q. How about your level of access, 10 what kind of access did you have? 11 A. I don't remember what my level 12 of access was in that, I did not go into the DEN 13 system to read anything, and I did not enter into 14 the DEN system. 15 Q. If you wanted information from 16 the DEN system, would you ask somebody else to 17 get it for you? 18 A. Definitely. 19 Q. Who would you generally ask? 20 A. The person that would -- that 21 had responsibility -- depending on what the 22 question was, it could be the DEN coordinator. 23 Q. Through the DEN system, did you 24 have the capability of determining how many Page 295 1 adverse events or 1639s were reported to the FDA, 2 sent to the FDA at any given time? 3 A. Yes. 4 Q. Other than the DEN system, were 5 there any other computer data bases that were 6 developed specifically to monitor adverse events? 7 And I'm not talking just spontaneous adverse 8 events. 9 A. The clinical trial data base, 10 of which I am not that familiar, would contain 11 information related to trial events. 12 Q. Was there another entity within 13 Lilly, another area within Lilly that handled the 14 collection reporting of non-serious clinical 15 trial adverse events or was that a portion of the 16 DEU also? 17 A. The non-serious trial events, 18 that was within the clinical trial data base. 19 Q. But my question is: Was there 20 another department or division or other entity 21 within Lilly that had responsibility of making 22 sure all that stuff got entered and was reported 23 properly, and things of that nature, or was that 24 a responsibility of the DEU? Page 296 1 A. No, that was not a 2 responsibility of the drug epidemiology, that 3 would have been a responsibility of what we call -- 4 well, actually the CRAs and physicians that have 5 responsibility for those products. 6 Q. So the DEU had no 7 responsibility whatsoever with regards to the 8 collection and reporting of non-serious clinical 9 trial adverse events? 10 A. Yes, that was not their 11 mission. 12 Q. Their mission was related 13 specifically to serious clinical trial event 14 reports and spontaneous adverse event reports? 15 A. Yes. 16 Q. Did you work in conjunction 17 with anybody during the time you read the DEU and 18 had responsibility for non-serious clinical trial 19 adverse events? 20 A. No, I did not. 21 Q. Was there one person while you 22 were at the DEU who had responsibility for 23 non-serious clinical trial Fluoxetine adverse 24 events? Page 297 1 A. No. 2 Q. The next few pages of Exhibit 2 3 appear to be reflections of NDA submissions from 4 the DEN for various periods of time; correct? 5 A. Uh-huh. 6 Q. You have to say yes or no. 7 MR. MYERS: Yes. 8 A. Yes, I'm sorry. 9 Q. When it says submissions, does 10 that mean submissions to the FDA, to your 11 knowledge? 12 A. NDA submissions would be 13 submission made to the NDA files at the FDA. 14 Q. And NDA submissions does, does 15 that indicate spontaneous adverse event reports 16 or could that be clinical trials that were run 17 under the NDA also? 18 A. That could include some study 19 reports that were submitted in a post-marketing, 20 after the marketing of the drug. 21 Q. So you're talking clinical 22 trials that were run after the marketing of the 23 drug? 24 A. Yes, that could include some of Page 298 1 those as well. 2 Q. Do you know a man named Mike 3 Dries, D-R-I-E-S? 4 A. Yes. 5 Q. Who is Mike Dries? 6 A. He worked at the FDA, as I 7 recall, in an area that dealt with the adverse 8 drug experience reporting area. 9 Q. Biostatus surveillance division -- 10 biostatistics surveillance division? 11 A. That sounds familiar. 12 Q. Did you ever have contact with 13 Mr. Dries with regards to Fluoxetine adverse 14 events? 15 A. I can't remember whether I ever 16 had conversations with him regarding that, I do 17 remember having conversations with him. 18 Q. If you could look at the page 19 marked Pz 1364 982 of Exhibit 2. 20 A. Okay. 21 Q. That's a memo or E-mail that 22 you wrote; correct? 23 A. Yes. 24 Q. And in that E-mail you talked Page 299 1 about a conversation that you had with Mike Dries 2 in which he gave you figures for total number of 3 adverse event reports made by Lilly to the FDA 4 for the years 1986 through 1990; correct? 5 A. Right. 6 Q. When you say the total number, 7 is that for all Lilly drugs or was that just for 8 Fluoxetine? 9 A. It looks like it relates to 10 total Lilly reports. 11 Q. What does it mean where you say 12 periodic on the third column over in the middle 13 of the page? 14 A. Those would be reports that are 15 sent in at either quarterly or annual basis, 16 according to the FDA regulations. Some reports 17 are required fifteen days, some are required to 18 be reported on what's called a periodic basis. 19 Q. Okay. To your knowledge did 20 the FDA have the capability of telling you the 21 total number of adverse events that were reported 22 under the IND of any drug? 23 A. I don't know, this group here 24 would not have access to that information from Page 300 1 what I recall. 2 Q. You're familiar with the FDA 3 spontaneous reporting system, are you not? 4 A. It depends on what the question 5 is, I guess. Yes, I know that there is one, yes. 6 Q. Okay. What is your 7 understanding of what the spontaneous reporting 8 system at the FDA is? 9 A. It's just a repository that 10 collects all of the reports that are required to 11 be submitted under the NDA regulations. 12 Q. So in the case of Fluoxetine -- 13 well, in the case of any drug, it would be 14 spontaneous adverse reports; correct? 15 A. Correct. 16 Q. It would also include any 17 serious adverse events that were reported as a 18 result of a clinical trial; correct? 19 A. Not necessarily, no. 20 Q. Are there situations where 21 adverse events that occurred during clinical 22 trials would be reported to the SRS? 23 A. The SRS? 24 Q. Spontaneous reporting system. Page 301 1 A. I'm sorry, the first part was? 2 Q. When I asked you if serious 3 adverse events resulting in a clinical trial 4 would be included in the data base at the FDA or 5 the SRS, and you said not necessarily. 6 A. Right. 7 Q. What I'm trying to find out is 8 in what situation would such an adverse event 9 occurring during a clinical trial be reported or 10 stored in that reporting system? 11 A. It would be in some, as I 12 recall, it would be some in a post-marketing 13 mode. 14 Q. What do you mean by 15 post-marketing mode? 16 A. After a drug was approved. 17 Q. I'm talking about adverse 18 events that occurred during clinical trials. 19 A. Right. 20 Q. So in what situations would 21 adverse events occurring in clinical trials 22 post-marketing be reported to the SRS or reported 23 in the SRS? 24 A. I can't remember all the Page 302 1 specifics to that, I do remember that the 2 attributes of that would be that they are 3 serious, unexpected and reasonably possibly 4 related. 5 Q. And whether or not an adverse 6 event is reasonably possibly related to a drug is 7 a determination that's made by the clinical 8 research physicians at Lilly; correct? 9 A. That's correct. 10 Q. And whether or not an event is 11 unexpected depends on what has been memorialized 12 in the package insert, package literature? 13 MR. MYERS: I object to the form only 14 because if it's a trial, there wouldn't be any 15 package literature. 16 Q. Okay, that's a good question. 17 How do you make a determination as to whether or 18 not an adverse event is unexpected if it occurs 19 during a clinical trial? 20 MR. MYERS: You weren't listening 21 yesterday. 22 MS. ZETTLER: Yes. 23 MR. MYERS: He went over that. 24 A. If there is no package Page 303 1 literature, it would be the clinical 2 investigation brochure. 3 Q. Oh. How about post-marketing 4 clinical trials, though, there is obviously a 5 package insert post-marketing, right? 6 A. Right. 7 Q. What would you look at from the 8 clinical trial standpoint, the investigator 9 manual or a package insert or combination? 10 A. As I recall, we looked at the 11 package literature, which, as I recall, was also 12 duplicated in the clinical investigation 13 brochure. But the package literature was the 14 primary document. 15 Q. So premarketing you would look 16 at the clinical investigation brochure, 17 post-marketing you would look at most likely the 18 package insert, but you could also look at the 19 clinical investigation brochure? 20 A. You would look at the U.S. 21 package literature, and then that information is 22 also put into the clinical investigation 23 brochure. But the intent was to use one document 24 after the drug is marketed. Page 304 1 Q. To your knowledge was 2 suicidality, suicide or suicide attempt 3 considered expected or unexpected at Lilly while 4 you were with the DEU? 5 A. Expected or unexpected? 6 MR. MYERS: I object to the form only 7 to the extent that you used the term considered 8 expected at Lilly. It's either in the insert or 9 it's not. 10 MS. ZETTLER: That's what I'm trying to 11 find out. 12 A. I'm sorry, your last part? 13 Q. My question is: To your 14 knowledge, while you were in the DEU, did Lilly 15 consider suicide, suicide attempt or suicidal 16 ideation expected? 17 MR. MYERS: Same objection. Tell her 18 if you know. 19 A. The only thing I can say is 20 that if it were in the literature and it 21 occurred, it would be expected, and I can't tell 22 you about the statements about whether it was or 23 not. 24 Q. And yesterday I think you Page 305 1 talked to Paul about the various areas within the 2 package insert that you would look to see if 3 something was listed, and I think it was like 4 contraindications, warnings, and there was one 5 other one, I can't remember now. 6 MR. MYERS: He said -- I remember, he 7 said adverse reaction, warnings and precautions 8 that we recall. 9 Q. Any other sections within the 10 package insert that you would look? 11 A. I had some question about 12 whether it was precaution. 13 Q. But you don't recall any other 14 sections where you would look? 15 A. Not offhand, no. 16 Q. Is that part of the FDA 17 regulations, in other words are there certain 18 areas that you look at in the package insert 19 that's dictated by the FDA to see if something is 20 expected? 21 A. I'm frankly not familiar with 22 that piece of it. 23 Q. Earlier you talked about 24 seriousness of an adverse event under the FDA Page 306 1 regulations being dictated basically by the 2 criteria set out by the regulations; correct? 3 A. Yes. 4 Q. And in most cases there's 5 pretty clear-cut indications, in other words 6 death, hospitalization, congenital anomaly, 7 cancer, and things that are pretty definitive, 8 right? 9 A. Correct. 10 Q. You also talked about with Paul 11 yesterday the category of life-threatening, which 12 I also believe is one of the serious categories 13 under the regulations, right? 14 A. Correct. 15 Q. And you weren't sure, and if 16 I'm wrong, I'm sure Larry will correct me, but I 17 believe you weren't sure yesterday what the 18 definition of life-threatening was, right? 19 A. That's correct, I wasn't sure 20 what definition we had applied to that. 21 Q. But there was a definition set 22 forth by the FDA regs as far as you know, right? 23 A. I believe that's correct. 24 Q. And there was, I believe, a Page 307 1 separate definition that was applied by Lilly 2 with regards to life-threatening? 3 MR. MYERS: I object to the form, I 4 don't think that's how it was said. 5 MS. ZETTLER: I believe what he said 6 was that he wasn't sure what the FDA definition 7 was, but that it was the one applied by Lilly was 8 probably broader? 9 MR. MYERS: There was some discussion 10 about the word eminent, I don't remember that, a 11 couple of times. 12 Q. Do you know who made the 13 decision as to whether or not an adverse event 14 fell under the category of life-threatening at 15 Lilly? 16 A. That would be the research 17 physician would be looking at that, would make 18 that judgment. 19 MR. SMITH: Let's take a break. 20 (A SHORT RECESS WAS TAKEN.) 21 Q. (BY MS. ZETTLER) Mister Noone, 22 at the bottom of the first page of Exhibit 2, in 23 the left-hand corner, it says Winword document? 24 A. Uh-huh. Page 308 1 Q. What is Winword? 2 A. I think Winword is a word 3 processing software package similar to Microsoft 4 Word or whatever. 5 Q. Word Perfect? 6 A. Yes, right. 7 Q. Were special requests or other 8 requests made of the DEN system all termed 9 Winword document? 10 A. I don't recall that they were, 11 no. 12 Q. Why would Leigh Thompson be 13 interested in the information discussed in the 14 first page of Exhibit Number 2? 15 MR. MYERS: Before he answers, that 16 probably calls on him to speculate as to what 17 Doctor Thompson was interested in. If he knows, 18 certainly he can tell you, but don't speculate as 19 to what Doctor Thompson wanted to know. If you 20 know, tell her. 21 A. I don't know. 22 Q. Did you ever have any 23 discussions with Doctor Thompson regarding 24 adverse events that were reported in the DEN Page 309 1 system? 2 A. Yes, I have. 3 Q. Did you ever have any 4 discussions with Doctor Thompson related to 5 adverse events on suicide or suicidal ideation 6 with Doctor Thompson? 7 A. No. 8 Q. When did Lilly become concerned 9 about the issue of homicidal ideation or violent 10 aggressive behavior and the use of Fluoxetine, if 11 you remember? 12 A. I don't remember all of those, 13 I just remember the Teicher article being 14 published that related to suicidal ideation, and 15 that was my first recollection of the question 16 being raised. 17 Q. About homicidal ideation also? 18 A. No, just suicidal ideation 19 related to the Teicher article. 20 Q. Have you ever discussed 21 homicidal ideation as it related to the use of 22 Fluoxetine with anybody at Lilly? 23 A. No. 24 Q. Have you ever been in a meeting Page 310 1 where that issue was discussed? 2 A. I don't recall being in a 3 meeting where that was discussed, no. 4 Q. Do you ever remember seeing an 5 increased frequency report generated with regards 6 to the issue of homicide and the use of 7 Fluoxetine? 8 A. I don't recall that, no. 9 Q. How about violent aggressive 10 behavior in general? 11 A. I don't recall that either. 12 Q. Okay. Let me make sure I have 13 this, I got pretty confused yesterday, that's 14 probably fairly evident at this point, but I want 15 to make sure I have all the procedures down for 16 the reporting of the various adverse events in 17 various situations. My understanding from 18 yesterday is that you had the category of adverse 19 events that occurred in clinical trials; correct? 20 A. Adverse category, right. 21 Q. And the serious adverse events 22 occurring in clinical trials were reported in the 23 DEN; correct? 24 A. Correct. Page 311 1 Q. And we talked already about the 2 various FDA regulations defining what's serious 3 and unexpected, right? 4 A. Right. 5 Q. But as far as an adverse event 6 that's reported or that occurs in a clinical 7 trial that's serious, that is the only category 8 that has to be met for it to be reported in the 9 DEN; correct? 10 A. Yes. 11 Q. It doesn't have to be 12 unexpected and it doesn't have to be reasonably 13 possibly related to the use of the drug? 14 A. That's correct. 15 Q. Then the other non-serious 16 adverse events are stored in the clinical trial 17 data base, the clinical trial adverse events. 18 A. That's correct. 19 Q. What are the mechanisms, other 20 than the 1639s that are generated with regards to 21 the serious adverse events that occurred during 22 clinical trials, what are the other reporting 23 mechanisms used by Lilly to report adverse events 24 occurring in clinical trials? Page 312 1 MR. MYERS: Without regard to 2 seriousness? 3 MS. ZETTLER: No, I'm concerned right 4 now with the non-serious. 5 Q. We know that the serious 6 adverse events are reported through 1639s, right? 7 A. Correct. 8 Q. And depending on the 9 seriousness of the adverse events, it could be a 10 three-day alert or fifteen-day alert; correct? 11 A. Ten days. 12 Q. But as far as the non-serious 13 adverse events that occurred in clinical trials, 14 what are the various ways that Lilly reports 15 those adverse events to the FDA? 16 A. I can give you a couple of ways 17 that's reported. One would be in annual reports, 18 which would include final study reports, and -- 19 on an NDA, a new drug application submission, 20 that information would be included in the new 21 drug application. 22 Q. So that's three different ways, 23 the annual reports, the clinical trial final 24 report and reported directly to the NDA? Page 313 1 A. Yes. 2 Q. Okay. How would it be reported 3 directly to the NDA? 4 A. How would it be reported 5 directly to the NDA? 6 MR. MYERS: How does it get sent in? 7 Q. Let me ask it this way: You 8 say that, and right now I'm still talking about 9 the non-serious clinical trial adverse events, 10 okay? 11 A. Okay. 12 Q. They can be reported as part of 13 the final report on a clinical trial? 14 A. Correct. 15 Q. It can be reported on an annual 16 report? 17 A. In an annual report that goes 18 to the agency, which includes lots of different 19 categories of information. 20 Q. And then you said it could be 21 reported directly to the NDA, or am I getting 22 confused? 23 A. I said in the new drug 24 application, at the time that you're making the Page 314 1 submission, you know, whatever the thing could be 2 two, three hundred, four hundred, five hundred 3 thousand pages or whatever. 4 Q. So it could be reported in the 5 NDA itself? 6 A. Yes. 7 Q. When you say annual reports, 8 what do you mean? 9 A. There are annual reporting 10 obligations that are required by the FDA, and 11 some of those apply to IND regulations, there's 12 an annual report, and there's an annual report 13 that's required for the NDA. 14 (DISCUSSION OFF THE RECORD.) 15 MS. ZETTLER: Could you read back the 16 last question and answer? 17 (THE COURT REPORTER READ BACK THE 18 REQUESTED TESTIMONY.) 19 Q. So there are annual reports 20 that must be submitted to the IND, and there are 21 annual reports that must be submitted to the NDA? 22 A. That's correct. 23 Q. Are these safety reports? 24 A. There are safety information Page 315 1 that's included in those reports, but I can't 2 recall all the categories of information that go 3 into those reports. 4 Q. Okay. How would a non-serious 5 clinical trial adverse event be reported to the 6 IND in annual reports? 7 A. Well, it would be included in 8 the study report on that given study. And it 9 seems to me there's other ways that go in as 10 well, but again, I'm not a content expert on 11 those reports. 12 Q. Did the FDA require a complete 13 description of each adverse event, non-serious 14 clinical trial adverse event, that was -- that 15 came up during the clinical trial, or is it a 16 matter of, you can say nausea, sixteen cases of 17 nausea, occurred during clinical trials during 18 this certain period of time? 19 A. I don't remember, I would have 20 to look at the requirements when you make the new 21 drug application submission and what's required, 22 and I would have to look at the annual reporting 23 requirements as well, but I don't recall. 24 Q. Do you recall ever being Page 316 1 involved in the creation of a document in which 2 every adverse event listed, say, for a particular 3 study was listed in detail as opposed to just 4 category? 5 A. In a report to the FDA, you're 6 saying? 7 Q. Right. 8 A. I can't recall that, no. 9 Q. Serious clinical trial adverse 10 events, we know already are reported via 1639s to 11 the FDA; correct? 12 A. Yes. 13 Q. Any other mechanisms for 14 reporting serious adverse events that occurred 15 during clinical trials to the FDA? 16 A. Well, certainly that's the main 17 mechanism. I can't recall whether we also 18 tabulated information in annual reports or not, 19 but I do know that we did send that type of form 20 in for the IND qualified serious reports. 21 Q. Okay. Certainly they would be 22 reported in a final report for a clinical trial, 23 would they not? 24 A. As a part of a clinical -- Page 317 1 Q. A clinical trial final report. 2 A. I would assume so, but I'm not 3 familiar with what the requirements are on that 4 report, whether it needs to be -- whether that 5 information needs to be included in there or 6 whether that information, by virtue of the fact 7 it's submitted in a fifteen-day period is the way 8 it's handled by regulation. 9 Q. Okay. On those 1639s that are 10 filed with regards to a serious adverse event 11 that occurs in a clinical trial, is there an 12 indication made on the 1639 that this was an 13 adverse event that occurred during a clinical 14 trial? 15 A. As I recall, there is, yes. 16 Q. Do you remember what that 17 indication was, how that's indicated on the 1639? 18 A. No, I would have to look at the 19 1639 to refresh my memory on that. 20 Q. Okay. Now, with regards to 21 spontaneous adverse events, generally all of 22 those adverse events are reported to the FDA 23 through a 1639, correct, regardless of whether or 24 not they're serious? Page 318 1 A. That's correct. 2 Q. The FDA requires that any 3 adverse events that Lilly becomes aware of must 4 be reported by Lilly to the FDA; correct? 5 MR. MYERS: Are we spontaneous now? 6 MS. ZETTLER: Yes, now we're in 7 spontaneous. 8 A. As I recall, that's true. 9 Q. Okay. What were some of the 10 ways that Lilly became aware of adverse events, 11 spontaneous adverse events, while you were in the 12 DEU? 13 A. How do we become aware of 14 spontaneous events? 15 Q. Right. 16 A. Sales reps would call, which we 17 covered yesterday, someone could write a letter, 18 a health care person could call, a patient could 19 call, people could write. 20 Q. When you say people could 21 write, do you mean doctors or patients? 22 A. Yes, it could be patients that 23 could write. 24 Q. Any other ways? Page 319 1 A. Those are the only ones that 2 come to mind right now, there might be others, 3 but that certainly gets the majority. 4 Q. How about literature? 5 A. Oh, yes, literature would be 6 another means, right. 7 Q. How about other media? 8 A. Correct, right. 9 Q. And when I say literature, I 10 mean popular press and industry related. 11 A. Yes, that's true. 12 Q. How about unpublished 13 manuscripts from people outside of Lilly? 14 A. Yes. 15 Q. In other words, 1639s were 16 filled out for Doctor Teicher's article, weren't 17 they? 18 A. Yes. 19 Q. How about other adverse event 20 collecting entities outside Lilly and the FDA? 21 A. It seems to me that catches the 22 majority of them, I can't think of any other ones 23 offhand. 24 Q. Were you aware of a situation Page 320 1 where Lilly filled out adverse event reports, 2 1639s, as a result of gaining information from 3 entities outside of Lilly or the FDA that 4 collected adverse event information on the use of 5 Fluoxetine? 6 A. Are you referring to media 7 again? 8 Q. No, like say do you know who 9 Doctor Inman is? 10 A. Inman, yes, I have heard that 11 name. Is he in the UK or something? 12 Q. Right. 13 A. Yes. 14 Q. What is your recollection of 15 Doctor Inman, who is he? 16 A. As I recall, he was a person 17 who devoted time in collecting adverse event data 18 in a post-marketing mode, and as I recall he was 19 in the UK. 20 Q. Okay. Did you ever talk to 21 Doctor Inman? 22 A. No. 23 Q. Did Lilly ever receive 24 information from Doctor Inman regarding adverse Page 321 1 events that he had collected related to 2 Fluoxetine? 3 A. I don't know whether it was 4 Fluoxetine, I do remember that we had received 5 information from him that we put into the Drug 6 Experience Network, but I don't remember which 7 products offhand. 8 Q. Was Doctor Inman's company, for 9 lack of a better word, prescription events 10 monitoring, PEM? 11 A. I don't know what the name of 12 it was. 13 Q. So you remember putting 14 information into the DEN as it resulted reports 15 by Doctor Inman, but you just don't remember if 16 it was specific to Fluoxetine or not? 17 A. Let me go back. I'm trying to 18 remember whether that data qualified as a 19 regulatory need. I do remember our reporting it, 20 but right now I can't recall specifically whether 21 those were in the form of 1639s or not. The 22 reason I'm saying that is that I'm not sure that -- 23 I can't remember whether that was a tabulation of 24 data that he had or whether it had to do with Page 322 1 specific patients. 2 Q. To your knowledge has anybody 3 from Lilly ever been in contact with Doctor Inman 4 with regards to suicidality related adverse 5 events collected by him? 6 A. I don't know. 7 Q. To your knowledge has Doctor 8 Inman ever been used as a consultant, so to 9 speak, on the causality relation of suicidality 10 events and the use of Fluoxetine? 11 A. I don't know that either. 12 Q. Let's go back to the computer 13 generated increased frequency reports. Earlier 14 you testified that that was based on a percentage 15 compared to how much -- how many units were sold; 16 correct? 17 A. Right. 18 Q. Who decided what percentage 19 that would kick in the frequency report generated 20 by the computer? 21 A. Say that question again. 22 Q. You said that to your knowledge 23 there was a percentage increase after which the 24 computer would generate this increased frequency Page 323 1 report; correct? 2 A. Uh-huh. 3 Q. Yes or no. 4 A. Yes. 5 Q. Who would decide what 6 percentage would, in effect, cause the computer 7 to generate an increased frequency report? 8 A. As I recall, we had just 9 established an algorithm that was applied across 10 all the products, and I don't remember now what 11 the algorithm was, but I do recall that it had to 12 do with the number of events that had occurred, 13 if it was a product less than three years old, in 14 one quarter versus the next, and you compared 15 that -- those were the numerators, and the 16 denominators were the number of units that were 17 sold on the product. 18 Q. Did that percentage change in 19 relationship to how long the product had been on 20 the market? 21 A. That shouldn't have any 22 factoring in that. 23 Q. Do you know if the percentage 24 change? Page 324 1 A. Did what percentage change? 2 Q. In other words, you said that 3 the increased frequency reports had to be 4 generated on a quarterly basis for a drug that 5 had been on the market for less than three years, 6 right? 7 A. Right. 8 Q. In that situation there was a 9 certain percentage increase compared to the 10 number of units sold of an adverse event that 11 would start the process of the generation of the 12 increased frequency report, right? 13 A. Uh-huh. 14 MR. MYERS: Yes. 15 A. Yes. 16 Q. Did that percent -- like let's 17 just use for an example, say, ten percent 18 increase, okay? 19 A. Okay. 20 Q. Compared to units sold. Was 21 that the same for increased frequency reports 22 that were generated after a drug had been on the 23 market longer than three years? 24 A. After a three-year period, I Page 325 1 believe our algorithm at that point was to 2 compare one year to the next as opposed to 3 quarter to quarter, and that tracked with our 4 periodic reports that went into the FDA quarterly 5 for anything that was under three years of age. 6 Q. Okay. But after the drug had 7 been on the market for three years, were you 8 still looking at it as a percentage increase 9 situation? 10 A. Yes, we were still looking at 11 increased frequency, are you seeing greater 12 percentage of occurrences now versus than what 13 you had earlier. 14 Q. Again, compared to the number 15 of units sold? 16 A. Right, versus the earlier 17 period. 18 Q. So say that in the earlier 19 period, the less than three-year period, you were 20 using a ten percent increase in the frequency of 21 a suicide, okay, would you still use that ten 22 percent increase in your determination of an 23 increase? 24 A. I don't know that ten percent Page 326 1 was a number that was given. The only thing I 2 can go back to is just say that if you had one 3 event reported, and you had a hundred units sold, 4 and the next period you had two events over a 5 hundred units sold, then that would be enough for 6 an increased frequency. I'm over-simplifying 7 that a little bit, but just to give you an idea. 8 Q. And what I'm trying to find out 9 is does that stay the same when you go into the 10 mode of a drug that's been on the market for 11 longer than three years? 12 MR. MYERS: She wants to know if the 13 triggering percentage, if you will, changes over 14 time that the drug has been on the market. 15 A. I don't recall that it did, 16 you're looking at different points in time. 17 Q. Have you ever heard of EARS 18 system, E-A-R-S? 19 A. Yes. 20 Q. Can you tell me what the EARS 21 system is? 22 A. That was a European reporting 23 system. 24 Q. A Lilly European reporting Page 327 1 system or a governmental reporting system? 2 A. As I recall, it was a Lilly 3 reporting system that linked into DEN, but it's 4 primary utility was for handling regulatory needs 5 on the European side of the bond. 6 Q. So it was really the European 7 equivalent to DEN? 8 A. To some extent, it was, but it 9 was linked into DEN anyway while it was in place. 10 Q. Is this something that was 11 phased out after DEN two came into existence? 12 A. As I recall, it was. In fact, 13 it might have even been phased out before that 14 time, but I can't recall what the specific timing 15 of that was. 16 Q. What's PADERS, P-A-D-E-R-S? 17 A. PADERS. I can't remember what 18 the acronym stands for, I thought that might have 19 been the possible increased frequency, but that's 20 PIFRS. PADERS, I used to know that, I don't 21 remember what it is now. 22 Q. Is that something that is a 23 Lilly acronym? 24 A. I believe that's right, yes. Page 328 1 Q. PIFRS is possible increased 2 frequency? 3 A. Frequency, right. 4 Q. Are PIFRS reports the quarterly 5 increased frequency reports we're talking about 6 or is that something different? 7 A. Yes, it's the same thing, it's 8 just an acronym that covers all increased 9 frequency regardless of what the interval is. 10 Q. In what situations would a 11 clinical research physician feel it would be 12 necessary to generate an interim increased 13 frequency report that you mentioned earlier? 14 MR. MYERS: Before he answers, let me 15 object to the form because it may call upon him 16 to speculate as to what would drive some other 17 person's investigation. If you know or if you 18 don't know, tell her that. 19 A. I can recall when it was -- 20 because of one product that we had that was a 21 seasonal product, it was very clear to the CRA 22 and to the physician that there was increased 23 frequency numbers without their even having run 24 the algorithm, so then they ran the algorithm Page 329 1 against it. 2 Q. Were any interim increased 3 frequency reports generated as a result of Doctor 4 Teicher's article, to your knowledge? 5 A. I don't know. 6 MR. MYERS: Off the record. 7 (DISCUSSION OFF THE RECORD.) 8 (PLAINTIFFS' EXHIBITS 3, 4 AND 5 9 WERE MARKED FOR IDENTIFICATION AND 10 RECEIVED IN EVIDENCE.) 11 Q. Why don't you turn to Exhibit 12 3. Exhibit 3 purports to be Lilly's Answers to 13 Interrogatories propounded by plaintiff, Linda 14 Ganote, G-A-N-O-T-E; correct? 15 A. Yes. 16 MR. MYERS: Do you represent her? 17 MS. ZETTLER: Frankly, I don't know, 18 Larry, I think so. 19 Q. Could you turn to the fifth to 20 the last page, at the top it says verification. 21 Is that your signature on that page? 22 A. Yes, it is. 23 Q. Did you personally answer these 24 interrogatories? Page 330 1 A. Did I personally answer them? 2 Q. Right. 3 A. No, I did not gather the 4 information together, no. 5 Q. Do you know who did? 6 A. No, I can't say that I could at 7 this point. 8 Q. Who told you that the fact 9 information set out in these Answers to 10 Interrogatories is true? 11 A. As I remember, it would have 12 been someone in our legal component. 13 Q. Someone in the legal department 14 at Lilly? 15 A. Right. 16 Q. Did you do anything to 17 investigate whether or not the facts that you had 18 no personal knowledge of that are set forth in 19 response to these answers were in fact true? 20 MR. MYERS: Before he answers, let me 21 object to the form only to the extent that what 22 he did or didn't do is set forth in the 23 verification. 24 MS. ZETTLER: No, I don't believe Page 331 1 that's true. 2 Q. Let's turn back to the 3 verification, then. The second paragraph, it 4 says I have read the the foregoing responses of 5 defendant, Eli Lilly and Company, a corporation, 6 plaintiff's first set of interrogatories, most of 7 the facts set forth in the responses are not 8 within my personal knowledge, having been 9 assembled and compiled by other employees within 10 Eli Lilly and Company, as to the facts, I'm -- as 11 to which facts I am informed and believe the same 12 to be true. The remaining facts are known by me 13 to be true. I'm asking you with regards to those 14 facts that you were told were true, that you had 15 no personal knowledge of, did you do anything to 16 investigate whether or not the facts set forth in 17 answers to these interrogatories are true? 18 A. If I had any question on those, 19 I would have, but if I had no question that would 20 lead me to the point of believing that there was 21 something wrong with it, then I would not have, I 22 would have accepted it as it was there. 23 Q. Okay. Did you question any of 24 the responses to any of these interrogatories? Page 332 1 A. I would have to go back and 2 look, that's a long time ago. 3 Q. Go ahead and take a look. 4 A. I don't remember any of these 5 that I had any questions on, most of them refer 6 back to the IND and NDA. 7 Q. Right, okay. If you turn to 8 page three, question number two, it asks for the 9 names of each and every employee at Lilly 10 involved in development testing on United States 11 FDA approval of Prozac. To your knowledge, are 12 all employees that were involved in the 13 development, testing or approval of Prozac by the 14 FDA listed in the NDA or IND? 15 MR. MYERS: Are you asking him if the 16 answer is different than the answer here? 17 MS. ZETTLER: No, I'm asking him 18 specifically if, to his knowledge, every employee 19 that worked on Prozac in development, testing or 20 regarding the FDA approval of the drug would be 21 listed in the IND or NDA? 22 A. Based on the way this question 23 here is worded, I would say that the answer is 24 correct. Page 333 1 Q. Why? 2 MR. MYERS: Wait a minute, let me 3 interpose, there are a bunch of objections to 4 these interrogatories, and answers were all made 5 subject to the objections, so your question 6 doesn't include the objections. He's answered 7 subject to the objections. 8 Q. My question is simply -- 9 MR. MYERS: I understand what your 10 question is. 11 Q. -- whether or not the names of 12 all Lilly employees who worked on the 13 development, testing or related to the FDA 14 approval of the drug would be listed in, let's 15 start with, the IND or NDA? 16 MR. MYERS: And I object to the form to 17 the extent that your question does not encompass 18 or contemplate numerous objections which are set 19 forth on the first couple of pages of the 20 interrogatory, that's my point. 21 Q. Can you answer the question, 22 Mister Noone? 23 MR. MYERS: Sure, he can answer if he 24 can. Page 334 1 A. I have no reason to doubt that 2 the answer is not correct. 3 Q. Does the FDA require that Lilly 4 provide them with a complete list of all 5 employees who are working on a drug that is 6 pending approval? 7 A. I don't know the answer to that 8 question. 9 Q. For instance, would your name 10 be included somewhere in the IND file or the NDA 11 file? 12 A. Would my name be included? 13 Q. Right. 14 A. I don't know that it would or 15 would not be, I don't know. 16 Q. So you don't know if all of the 17 names of Lilly employees that worked on the 18 development, testing or FDA approval of Prozac 19 would be included in the IND and NDA? 20 A. I wasn't involved with the 21 development, testing or approval of the drug. 22 Q. Safety isn't an element of the 23 approval of the drug for marketing? 24 MR. MYERS: That's a different Page 335 1 question. 2 A. Yes. 3 Q. Is safety an element that's 4 taken into consideration in the approval of the 5 drug for marketing? 6 A. There's safety information, 7 yes, that's in there, right. 8 Q. Safety is taken into 9 consideration in the testing and development of 10 the drug, isn't it? 11 A. That's correct. 12 Q. And spontaneous adverse reports 13 and serious clinical trial adverse reactions are 14 an element of safety, aren't they? 15 A. The question is each and every, 16 in the development, testing or United States Food 17 and Drug Administration approval -- I'm still 18 looking at the question, and it looks to me like 19 it's stating that it has to do with the approval 20 of Prozac, which was approved before I ever got 21 involved with the safety of the drug, which was 22 in '88. 23 Q. What makes you think that this 24 has to do specifically with the approval of the Page 336 1 drug? 2 MR. MYERS: Because that's what it 3 says. 4 MS. ZETTLER: Where? 5 A. Approval of Prozac. 6 Q. It says as to each and every 7 employee of Lilly involved in the development, 8 testing or United States Food and Drug 9 Administration approval of Prozac. 10 A. I was not involved with 11 development and testing. Approval involves 12 safety, but I came into the area after the drug 13 was approved. 14 Q. But you also had some 15 responsibility for the section that collected 16 clinical trial serious adverse events, did you 17 not? 18 A. I had no responsibility for 19 that area before the drug was approved. 20 Q. How about after the drug was 21 approved? 22 A. I had responsibility for the 23 Drug Experience Network, correct. 24 Q. And that included serious Page 337 1 adverse events that occurred in clinical trials 2 of Prozac. 3 A. Right. 4 Q. That would encompass testing 5 the drug, correct, a clinical trial is done to 6 test the drug, is it not? 7 MR. MYERS: I object to the form only 8 to the extent that your question started out with 9 the premise that he was involved in development 10 and testing. He's already testified that he 11 wasn't. If you're asking him in the abstract, 12 does that involve -- 13 MS. ZETTLER: I think the question is 14 pretty clear. 15 MR. MYERS: I don't think it is at all, 16 I object to the form. If you can answer it, 17 answer it. 18 A. I can't answer it. 19 Q. You can't answer whether or not 20 a clinical trial comprises a testing of the drug? 21 A. In that definition, a 22 conducting of a clinical trial would involve 23 testing the drug, right. 24 Q. Okay. Now, you're assuming Page 338 1 that question number two is asking you 2 specifically about development and testing of the 3 drug before FDA approval; correct? 4 MR. MYERS: I object to the form, that 5 is not what he said, Nancy. 6 MS. ZETTLER: Then what did he say? 7 MR. MYERS: He said as follows: I was 8 not involved in the development, I was not 9 involved in the testing, and I wasn't involved in 10 the approval because I came on board in that job 11 after it was approved. 12 MS. ZETTLER: Right, but he's also 13 assuming the question only encompasses only that 14 period of time before the drug was approved, and 15 that's clearly not what the question asks. 16 Q. My original question is: To 17 your knowledge, would the IND and NDA include all 18 of the names of Lilly personnel who were involved 19 in the development, testing or FDA approval of 20 Prozac? 21 MR. MYERS: Same objection as to the 22 form. Answer it if you can. 23 A. Well, if one wanted to apply a 24 definition to this -- to the broad extent that I Page 339 1 hear you stating it, you almost wind up with 2 everybody in the whole company on the list at 3 some point. I mean that's -- 4 Q. Everybody in the whole company 5 at some time or another was involved in the 6 development, testing or FDA approval of Prozac? 7 A. Well, they would work in an 8 area where some of these things were done, and I 9 see no -- I see some proximate -- I just don't 10 know what the sense of the question is. If it's 11 wanting to say did anybody who ever touched the 12 drug, practically, does their name need to be in 13 the IND and NDA. It seemed like that was -- I 14 just don't see the relevance of interpreting it 15 that narrowly. 16 Q. Your job isn't to interpret the 17 question, your job is to answer the question. 18 MR. MYERS: That's right, and there's 19 been objections urged as to the form of the 20 question in these interrogatories on the first 21 two pages. 22 MS. ZETTLER: I'm just asking him a 23 simple question, Larry, of whether or not the IND 24 and NDA contain the names of all of those Lilly Page 340 1 employees who have worked on development, testing 2 or FDA approval of Prozac. 3 Q. Can you answer that yes or no 4 question? 5 MR. MYERS: Same objection, it may or 6 may not be. 7 A. Give me the question one more 8 time. 9 Q. To your knowledge, does the IND 10 and the NDA include all of the names of those 11 Lilly employees who worked on the development, 12 testing or FDA approval of Prozac? 13 A. I guess I have to say I don't 14 know. 15 Q. Go to question number three on 16 the next page. The question asks for information 17 about physicians or medical professionals who 18 contacted Lilly by phone, mail or other written 19 communication with respect to side effects or 20 adverse reactions for patients for whom Prozac 21 has been prescribed; correct? 22 A. Right. 23 Q. And the answer is: Lilly makes 24 objections on the ground that it requests Page 341 1 information which is required to be kept 2 confidential under FDA regulations. And then the 3 answer goes on to say that all adverse reaction 4 reports reported to Lilly concerning Prozac are 5 contained in the NDA for Prozac, as described in 6 the answer to interrogatory number two; correct? 7 A. Correct. 8 Q. That's not entirely true, is 9 it? 10 A. What's not true? 11 Q. There are some adverse events 12 that are submitted to the IND, aren't there, like 13 we talked about this morning? 14 MS. ZETTLER: Let the record reflect 15 that the witness is conferring with counsel. 16 MR. MYERS: He's not, he's reading to 17 himself. 18 A. I'm trying to read this. 19 MR. MYERS: If he was conferring, I 20 can't understand what he's saying, 21 A. There may be information 22 contained in the IND that may not be in the NDA. 23 Q. Okay. Do you know for a fact 24 that all adverse reactions or side effect Page 342 1 information reported to Lilly is contained in the 2 NDA? 3 MR. MYERS: I object to the form 4 because it ignores the objections, the general 5 and specific objections. If you know, tell her. 6 A. I'll read over this question 7 again. Give me the question again. 8 (THE COURT REPORTER READ BACK THE 9 REQUESTED TESTIMONY.) 10 A. I have to go back and take a 11 look. As I recall, Prozac is the name of the 12 product that was approved, Fluoxetine is the 13 generic name that was pursued that was filed to 14 INDs. And the question relates again back to -- 15 I'm looking at Prozac, and there may be some 16 clinical studies that might have been filed to an 17 IND. 18 Q. Well, the initial IND that was 19 filed with regards to Fluoxetine was for the use 20 of Prozac in treating depression, was it not? 21 A. I don't remember how many INDs 22 we had filed at the time. 23 Q. There was an IND that was filed 24 related to Prozac for the use of depression; Page 343 1 correct? 2 A. Right, there was one. 3 Q. So is it your testimony that 4 the IND would not contain any adverse reaction or 5 side effect information regarding Prozac for the 6 use of depression that would not also be 7 contained in the NDA? 8 A. There would be information 9 contained in the IND that would not be in the 10 NDA, you're saying? 11 Q. Right. 12 MR. MYERS: Any kind of information? 13 MS. ZETTLER: No, side effect or 14 adverse reactions. 15 MR. MYERS: I object to the form on the 16 same basis as the last question. 17 A. I don't know, I can't answer 18 the question. 19 Q. But you answered it here, 20 didn't you? 21 A. Pardon me? 22 Q. You answered it here in the 23 exhibit? 24 A. Yes, I read this question over, Page 344 1 and as it had indicated on the statement in back, 2 some of the facts I was aware of, other facts 3 that were assembled and brought together by other 4 employees, and I was informed of those and 5 believed them to be true. 6 Q. But your personal experience as 7 an employee at Eli Lilly has taught you that 8 there are submissions to the IND that are not 9 made to the NDA; correct? 10 A. There are some what? 11 Q. Submissions made to the IND 12 that are not necessarily made to the NDA. 13 A. There are submissions made to 14 the IND that would not necessarily be made to the 15 NDA. 16 Q. And a part of those submissions 17 that are made to the IND that would not 18 necessarily be made to the NDA would include 19 safety aspects; correct? 20 A. It could. 21 Q. And it also could include 22 records of adverse events, could it not? 23 A. They could. 24 Q. Could you turn to page six, Page 345 1 please, question ten. If somebody were looking 2 to find out what institutions or research 3 facilities had contracts with Lilly to perform 4 clinical testing or laboratory evaluations of 5 Prozac, and they went to the IND or NDA and those 6 names were blacked out, there would be no way to 7 tell who those people were or those facilities 8 were, would there? 9 A. I would assume that's the case, 10 yes. 11 Q. Would you look at Exhibit 4, 12 please. If you could go to page seven. There's 13 a signature line with your name on it on that 14 page, is there not? 15 A. Yes. 16 Q. But there's no signature on 17 that page, is there? 18 A. That's correct. 19 Q. Has anybody ever asked you to 20 sign these answers to interrogatories? 21 A. I don't know. 22 Q. Why don't you take a look and 23 read those questions and answers. Before you do 24 that, let me ask you this, maybe we can Page 346 1 short-circuit this. Do you have any specific 2 knowledge as to the events involved in the 3 Wesbecker shootings down in Louisville, Kentucky? 4 A. Very peripheral. 5 Q. Tell me what you know. 6 A. I understand that he shot and 7 killed a bunch of people. 8 Q. Anything else? 9 A. I understood that there was, 10 from what I had read, that he had taken some 11 Prozac at some point. 12 Q. Anything else? 13 A. That's about it. 14 Q. Okay. Go ahead and take a look 15 at these interrogatory answers. Does that 16 refresh your recollection as to whether or not 17 anybody ever asked you to sign these 18 interrogatory answers? 19 A. I don't remember seeing this. 20 Q. Do you have any specific 21 knowledge of any of the facts that are set forth 22 in response to these interrogatories? 23 A. Just a limited amount of 24 information. Page 347 1 Q. What information in here do you 2 know or did you know? 3 A. Well, I recognize the 4 individual's name. I'm not sure what else I 5 might have recognized. 6 MR. RUIZ: Nancy, are these 7 answers to interrogatories in the Wesbecker case? 8 MS. ZETTLER: Fentress, right. 9 Q. Do you sign answers to 10 interrogatories in other actions, these cases, 11 any other Prozac cases? 12 A. Have I signed them? 13 Q. Yes. 14 A. Yes. 15 Q. Do you know why you've been 16 asked to sign these answers to interrogatories? 17 A. Because I was the formal 18 custodian of the files. 19 Q. Did you make a search of the 20 files in order to answer these interrogatories? 21 A. Not personally, no. 22 Q. Do you know for a fact that 23 somebody else made a search of the documents in 24 your control? Page 348 1 A. I'm informed by others that 2 people had been doing that, yes. 3 Q. Specifically in response to 4 answers to interrogatories in this case, the 5 Fentress case? 6 A. Specifically in regards to the 7 Wesbecker case? 8 Q. Right. Not documents 9 specifically in that regard, but made a document 10 search specifically in regard to answers to 11 interrogatories filed in this case? 12 A. I was informed that that was 13 done, yes. 14 Q. Who did that? 15 A. Our legal staff would have been 16 involved with that. 17 Q. How long did it take to search 18 the records to respond to these interrogatories? 19 A. I have no idea. 20 MR. MYERS: A long time, weeks and 21 weeks, months. 22 Q. Do you know when these 23 interrogatories were originally served on the 24 defendants, on you guys? Page 349 1 MR. MYERS: Let me object to the form. 2 There's a certificate of service, Nancy, it would 3 say that. I mean he isn't going to know that. I 4 mean the record will speak for itself somewhere. 5 MS. ZETTLER: If he doesn't know, he 6 can say he doesn't know. 7 A. I don't know. 8 MR. MYERS: I think the question is a 9 waste of time, really. 10 MS. ZETTLER: I'll use one of your 11 favorite phrases, that's your interpretation. 12 Q. If you can look at Exhibit 5. 13 A. Do you want me to read through 14 the whole thing? 15 Q. No, unless you feel more 16 comfortable answering questions on it by reading 17 through it, it's up to you. 18 MR. MYERS: Why don't you try some 19 questions and let's see how we do. 20 Q. Okay. Question number two on 21 page three. 22 A. On page? 23 Q. Question number two on page 24 three. It basically asks if you made a due and Page 350 1 diligent search of documents and have spoken with 2 agents, servants or employees of Lilly to respond 3 to these interrogatories, and you've just 4 testified that you didn't personally make a 5 search of documents; correct? 6 A. That's correct. 7 Q. Did you speak with any 8 employees of Lilly to gain information to respond 9 to these interrogatories? 10 A. As these interrogatories come 11 over from legal counsel, I have discussions with 12 them about that they have done that, but that's 13 basically about it unless I have some specific 14 questions of things that I know about, and if I 15 would feel that there's some clarification needed 16 or if I have reason to understand something 17 otherwise, then I would change the answer. 18 Q. Do you have a specific 19 recollection of questioning any of the answers 20 set forth in Exhibit 5? 21 A. I really don't, because I got a 22 lot of interrogatories, and for me to try and 23 look at one and say that that was the one I had 24 the questions on, I would not be able to answer Page 351 1 that. 2 Q. Do you recall having questions 3 regarding answers to interrogatories on more than 4 one occasion? 5 A. Getting interrogatories on more 6 than one occasion? 7 Q. No. Do you recall having 8 questions regarding answers set out by the Lilly 9 legal department in response to interrogatories? 10 MR. MYERS: Has he ever had any 11 questions? 12 Q. Right. Have you ever had any 13 questions with regards to answers set out by the 14 legal department at Lilly with regards to any 15 Prozac interrogatories? 16 A. Yes, I have. 17 Q. How often does that happen? 18 A. I couldn't tell you how many 19 times that's happened. First of all, I couldn't 20 tell you how many interrogatories that I have 21 been given. I have been given an awful lot 22 because they all come to me, because at that time 23 I was custodian of the files, so I was the 24 designated representative to deal with that Page 352 1 information. 2 Q. What did your job as custodian 3 of the files entail? 4 A. The files that were -- the IND 5 and NDA files were in my area, and my staff 6 provided that information to the FDA and then 7 kept a record of it. And it has been -- since 8 these questions cut across a broad number of 9 people, the intent of the company was to have one 10 person sign off on that, and I was the person 11 that volunteered to do that. 12 Q. You volunteered to do it? 13 A. I was asked, and I volunteered 14 to do it, yes. 15 Q. Who asked you? 16 A. It was legal counsel, and it 17 was at some time after one of my predecessors had 18 retired -- was getting ready to retire. 19 Q. Was that before or after you 20 became manager of the DEU? 21 A. I was in the -- it was sometime 22 probably in, if I had to guess, maybe around '85 23 or so, maybe '86 -- or '86 or so. 24 Q. And the question was to become Page 353 1 custodian of IND and NDA? 2 A. Right, the person who did that 3 before was retiring. 4 Q. Who was that? 5 A. A fellow by the name of Ed 6 Burroughs. 7 Q. Specifically what did you do to 8 put together these answers to interrogatories, 9 what was your specific responsibility in that 10 respect? 11 A. I read through all the answers 12 that I was given, and if I had knowledge of 13 something that was different, then I would 14 question that. If I had knowledge and knew that 15 the question was on track with what I had, then 16 it would be fine. If there were things that I 17 was not aware of, then as it indicated on the 18 other sheet, then I would assume that those facts 19 were true. 20 Q. Would you make it your business 21 to check to make sure that the facts were true by 22 speaking to somebody else or making an 23 independent investigation? 24 A. No, that would take -- I mean Page 354 1 that would be probably a two or three-fold 2 full-time job in my estimate because we already 3 had people that did that, so that wouldn't seem 4 to make sense. 5 Q. Why, to your knowledge, didn't 6 one of the people who actually did that, 7 gathering and setting up information in response 8 to these interrogatories, sign these 9 interrogatories instead of you? 10 A. Why didn't they? 11 Q. Right. 12 A. I can't completely answer that, 13 I think it's -- it would go back to the time that 14 I volunteered to take it. I think there was an 15 intent to try to have all -- since any 16 interrogatory is going to cut across typically 17 lots of areas in the company, the corporation 18 really felt that it was more relevant to have one 19 person that could sign off on that. 20 Q. To your knowledge it was the 21 legal department at Lilly that undertook the task 22 of actually formulating the answers to the 23 interrogatories? 24 A. Gathering the information and Page 355 1 formulating the answer, right. 2 Q. To your knowledge, which Lilly 3 employees were approached with regards to 4 discussing these answers, in other words, who was 5 approached in the various areas to provide 6 information to respond to these answers to 7 interrogatories? 8 A. I don't know. 9 Q. So basically you took the word 10 of whoever you talked to in the legal department 11 as to whether or not that task was actually done? 12 A. Right, I had no reason to doubt 13 them. 14 Q. How familiar are you with the 15 IND, NDA? 16 A. Familiar with what IND, NDA? 17 Q. The Prozac IND, NDA, how 18 familiar are you with it? 19 A. Well, familiarity would relate 20 to substance. Are you talking about substance, 21 the framework of the IND, NDA, the numbers of 22 pages or what? 23 Q. Everything. Let's start with 24 substance, how familiar are you with the Page 356 1 substance? 2 A. Probably not very. 3 Q. How familiar are you with the 4 structure of the IND, NDA? 5 A. I would have some knowledge of 6 that. 7 Q. What knowledge do you have? 8 A. That there are annual reporting 9 requirements, that there are requirements to 10 submit an IND to the FDA prior to initiating 11 studies in healthy human subjects, that you need 12 to wait thirty days before you start those up if 13 you haven't heard from the FDA. 14 Q. What are your specific 15 responsibilities with regards to your position as 16 custodian of the IND, NDA? 17 A. The files were kept in the 18 regulatory services area. We had responsibility 19 for that area, and also when the volume became 20 appreciable for the areas where the documents 21 were stored. 22 Q. What about when the volume 23 became appreciable. 24 A. When the volume what? Page 357 1 Q. You said also when the volume 2 became appreciable. 3 A. We didn't keep them in that 4 immediate file, we had another file in another 5 facility where we kept those. 6 Q. So you've done a good job of 7 describing the existence and volume of the IND, 8 NDA, but I still don't think you told me what 9 your responsibilities were with regards to 10 maintaining the files or anything like that? 11 MR. MYERS: Let me just object to the 12 form. You just didn't listen to what he said. 13 He said he had responsibilities for the 14 regulatory services area where the files were. 15 MS. ZETTLER: Right. But I want to 16 know specifically what his duties as custodian 17 were. 18 Q. We know that it was kept in the 19 regulatory services area, and it ended up 20 overflowing into more than one area, and I want 21 to know what your specific responsibilities with 22 regards to keeping those files were, if any. 23 A. My staff maintained all those 24 files, they were the ones who sent the Page 358 1 information off to the FDA, and they would keep a 2 duplicate copy of whatever was sent to the FDA on 3 the IND and NDA side. 4 Q. So it was really a matter of 5 keeping the file, so to speak? 6 A. Right, it's a record-keeping 7 function. I'm not a content expert, it was just 8 a record-keeping function. 9 Q. Who would be a content expert 10 on the IND, NDA at Lilly? 11 A. The people that would be 12 involved in whatever studies that were being -- 13 that were involved. 14 Q. How about Doctor Talbott, Max 15 Talbott? 16 A. I wouldn't say that he would be 17 a content expert, no. 18 Q. How about Doctor Zerbe? 19 A. I can't remember his entire -- 20 he had a number of different roles as Prozac was 21 around for a long time, so he may have been a 22 content expert on that. 23 Q. How about Leigh Thompson? 24 A. He probably would have been a Page 359 1 content expert on that as well. 2 Q. Do you know why either Doctor 3 Zerbe or Doctor Thompson were asked to sign the 4 interrogatory answers? 5 MR. MYERS: Why they didn't do it 6 instead of him? 7 MS. ZETTLER: Right. 8 A. We have always just had the 9 custodian of the files sign off on that. 10 Q. Has that been your experience 11 with other drugs manufactured by Lilly? 12 A. Yes, I signed off on the rest 13 of them as well. 14 Q. Other drugs or other answers to 15 interrogatories with regard to Prozac? 16 A. Other interrogatories that were 17 done during this period were sent to me, I know 18 of none that someone else might have signed 19 unless I didn't happen -- if I happened to be out 20 of town, then maybe somebody else signed it. 21 Q. But I'm asking you have you 22 ever signed interrogatories filed in cases 23 regarding other drugs other than Prozac or 24 Fluoxetine? Page 360 1 A. Yes. 2 MR. MYERS: He said yes. 3 A. Yes. 4 Q. And you're responsible for 5 maintaining the IND, NDA files on those drugs as 6 well? 7 A. Yes. 8 MR. MYERS: He was. 9 A. I was, correct. 10 Q. Is there anybody else that acts 11 as custodian of INDs or NDAs for any drugs that 12 you do not act as custodian for? 13 MR. MYERS: Did not act as? 14 MS. ZETTLER: Did not. 15 A. Could I ask you, could you slow 16 your questions down, I'm having a hard time. 17 MR. MYERS: She talks fast. 18 A. Say your questions slower, 19 please. 20 Q. Sure. Is there anybody else 21 that, while you were acting as custodian of the 22 IND, NDA for Fluoxetine -- 23 A. Right. 24 Q. -- was there anybody else Page 361 1 acting in that capacity for the IND, NDA for 2 other drugs manufactured by Lilly? 3 A. No. 4 Q. So you were the custodian for 5 all INDs, NDAs for all drugs manufactured by 6 Lilly across the board? 7 A. That's correct. And again, the 8 reason for that, there needed to be a focus on 9 that, and it was logical in our organizational 10 sense to have the person who headed up that area. 11 I took it on as a department head and continued 12 in that as I was at the manager level. 13 Q. Did you have any specific or 14 general responsibilities with regards to the 15 document collection requested by the legal 16 department at Lilly with regards to Fluoxetine, 17 in other words where everybody had to send their 18 documents to Lilly? 19 A. Yes, I was asked to provide 20 whatever documents that I might have had in my 21 own personal files to legal as well. 22 Q. Okay. Other than that, did you 23 have any responsibilities with regards to like 24 helping run the data -- the document collection Page 362 1 or anything of that nature? 2 A. No. 3 Q. When did you first have to turn 4 over documents to the legal department at Lilly? 5 A. I don't remember, I just 6 remember the document -- or the request going 7 out, and we were beginning -- we were having to 8 begin purging our files at that point. 9 Q. Were there any documents that 10 they excluded for that request? 11 A. Not that I can recall. 12 Q. It's my understanding that 13 periodically they asked you to turn over any 14 additional documents that have been generated 15 regarding Fluoxetine that are in your, your 16 meaning the employees, possession; correct? 17 A. Right. 18 Q. Have they excluded documents in 19 that request, and I'm not talking about documents 20 that have already been turned over -- 21 A. I don't know of any time that 22 any documents were excluded in the request if 23 they related to Fluoxetine. 24 Q. Do you maintain any of your Page 363 1 documents or files on computer disks? 2 A. Floppy disks? Yes, I do have 3 some documents -- well, I think I do, yes, I 4 think I do have some, yes, I do. 5 Q. Related to Fluoxetine? 6 A. No. 7 Q. Have you ever kept any 8 Fluoxetine related documents on floppy disks? 9 A. Not that I can ever recall, I 10 don't do much on floppy disks to begin with. 11 Q. To your knowledge, have you or 12 anybody that worked under you in the DEU turned 13 over documents to the legal department at Lilly 14 on floppy disks? 15 A. I don't know that they did or 16 they did not. 17 Q. Have you ever heard of a 18 gentleman named John Graedon, G-R-A-E-D-O-N? 19 A. That doesn't sound familiar. 20 Q. How about Richard Huddleston? 21 A. Yes. 22 Q. Who is Richard Huddleston? 23 A. Richard Huddleston worked for 24 me in the drug epidemiology unit as a clinical Page 364 1 research administrator. 2 Q. Is he still with Lilly? 3 A. Yes, he is. 4 Q. Do you know where he is now? 5 A. Yes. 6 Q. Where is he? 7 A. An area called medical quality 8 assurance. 9 Q. What does he do in MQA, do you 10 call it MQA? 11 A. Right. 12 Q. What does he do for MQA? 13 A. He's a medical quality 14 assurance representative. 15 Q. He's one of the people that 16 goes out to the clinical trial sites and does 17 audits of documents and information out there? 18 A. He does those things, yes. 19 Q. Does he do anything in-house? 20 A. Yes. They have -- that staff 21 has responsibility in-house as well. 22 Q. Do you recall a MQA audit of 23 the DEN data base? 24 A. Yes. Page 365 1 Q. When did that occur? 2 A. I think there were a couple of 3 those. 4 Q. When was the first one? 5 A. I can't recall when we had the 6 first one. 7 Q. Was it before or after the 8 Teicher article came out? 9 A. I can't remember. 10 Q. Was it while you were in the 11 DEU? 12 A. Yes. 13 Q. Was it before you left the DEU? 14 A. I know there were some that 15 took place while I had the DEU, yes. 16 Q. How many took place while you 17 had the DEU? 18 A. I would say at least two. 19 Q. Are you aware of any other 20 audits that were performed on the DEN when you 21 were not with the DEU? 22 A. When I was not with the DEU, so 23 that was either before or after. I'm not aware 24 of that. Page 366 1 Q. The first audit that was done 2 while you were with the DEU, why was that done? 3 A. It was a standard -- it was an 4 area of focus, the division wanted to assure that 5 everything there was operating appropriately. 6 Q. What division? 7 A. The medical division and also 8 the quality assurance division. 9 Q. Was this a routine audit? 10 A. Yes. 11 Q. Was it done in response to a 12 particular problem with the DEN system? 13 A. Not that I'm aware, no. 14 Q. What changes, if any, were made 15 with the DEN as a result of the first audit? 16 A. I don't remember what changes 17 that were made. I do recall that there were no 18 major issues, but there were some changes that 19 were made, but I don't remember what those were 20 at this point. 21 Q. Was that audit performed before 22 or after 1990? 23 A. I don't recall the timing. 24 Q. The second audit that was done Page 367 1 while you were with the DEU, do you remember when 2 that took place? 3 A. No, I don't remember the dates 4 on that. 5 Q. Why was that one done? 6 A. As I recall, it was again 7 because the -- it was a division focus, also a 8 quality assurance focus, those are two separate 9 areas, and that was one of the most important 10 areas to the company, and, so, we were running 11 more routine audits through there than we were 12 anyplace else that I was aware of. 13 Q. How often were the audits done? 14 A. I couldn't tell you how many 15 were done in total there, I do remember two that 16 were done. 17 Q. Is it a policy to do them 18 within any given period of time, like say every 19 year or every two years? 20 A. There's no policy that dictates 21 how frequently that type of function occurs. 22 Q. The first audit that you 23 remember, was that done on DEN one or DEN two? 24 A. I don't remember for sure. Page 368 1 Q. Was there a written report done 2 by MQA on that audit? 3 A. I think every time they have 4 done an audit, they had some sort of a written 5 report. 6 Q. What happened as a result of 7 those reports as far as responding to any issues 8 that were raised or things of that nature? 9 A. The standard procedure is they 10 provide the observations, you respond to those 11 observations to, one, authenticate their 12 accuracy. Because of the complexity of all of 13 that, sometimes there needs to be communication 14 that takes place because of that. And then if 15 there are changes that they have recommended, 16 then we make a statement about what we will do 17 relative to those recommendations, and then there 18 would be a follow-up period at some point. 19 Q. Were you involved in responding 20 to the MQA audits? 21 A. Yes. 22 Q. What did you do personally in 23 response to the MQA audits? 24 A. Typically what I would do is to Page 369 1 assign a couple of people to look at all the 2 information and have them understand the 3 observations that were made and the suggestions 4 that were made, and then that staff would then 5 put together a response and then I would review 6 it before we sent it on to the medical quality 7 assurance people, and usually with my management 8 as well. 9 Q. So it was a supervisory 10 capacity as opposed to -- a supervisory and 11 review capacity as opposed to a hands-on 12 searching for answers capacity? 13 A. Generally that's true, although 14 I took a lot of interest in that and asked an 15 awful lot of questions, just because of the 16 nature of the questions. 17 Q. Questions -- you asked a lot of 18 questions of your staff? 19 A. Right. 20 Q. To your knowledge does the FDA 21 have access to the DEN data base? 22 A. Pardon me? 23 Q. Does the FDA have access to the 24 DEN data base, and I'm not talking about can they Page 370 1 call it up on their computer, but if they wanted 2 to come in and take a look at the data base as it 3 exists, could they do it? 4 A. I don't know if they could or 5 not. 6 Q. Did they ever ask you? 7 A. I don't remember that they 8 have, no. 9 Q. Have they ever asked to audit 10 the DEU at Lilly? 11 A. It was my understanding that 12 they did look at the DEU at one point, yes. 13 Q. Was that before or after you 14 were involved with the DEU? 15 A. That was after. 16 Q. Do you know why they asked to 17 do that? 18 A. It was my understanding it was 19 a routine. 20 Q. Do you remember what year that 21 was done? 22 A. It might have been 1993, either 23 late '92 or '93 sometime. 24 Q. Who was in charge of the DEU Page 371 1 when that audit took place, if you know? 2 A. Earlene Ashbrook would have 3 been the manager of the area. 4 Q. Were you asked to participate 5 in any way in that audit? 6 A. No, I just heard about it, that 7 it was occurring, then I heard afterwards that it 8 had occurred. 9 Q. What did you hear about what 10 occurred? 11 A. I heard that it was 12 outstanding, that we got extremely good marks. 13 Q. Do you know what areas the FDA 14 looked at in the audit, specific areas within the 15 DEU? 16 A. No, I don't. 17 Q. Did they have any criticism 18 whatsoever? 19 A. As I understood it, there was 20 no four eighty-three that was issued, which would 21 indicate there would be no criticism. 22 Q. What's a four eighty-three? 23 A. That's a report -- when FDA 24 comes in to conduct an inspection, and if they Page 372 1 find areas for improvement or shortcomings, then 2 they issue a form FD four eighty-three which 3 indicates what their observations were or what 4 their suggestions are. 5 Q. Was that an unannounced audit 6 or was that an announced audit? 7 A. I don't know. 8 MS. ZETTLER: Can we take a quick 9 break? 10 MR. MYERS: Sure. 11 (A SHORT RECESS WAS TAKEN.) 12 Q. The audit that we were just 13 talking about, was that an audit of the entire 14 DEU or was that specifically the DEN? 15 A. I don't know what the full 16 extent of it was, but my impression was that they 17 had looked at the system as well as talked to 18 people about procedures and all the other things 19 that they did. 20 Q. Did that audit encompass the 21 clinical trial data base for adverse events? 22 A. I don't believe that it did. 23 Q. Was there a specific clinical 24 trial adverse events data base or was that Page 373 1 something that was encompassed within the 2 clinical trial data base? Does that make sense? 3 A. Yes. I don't recall that we 4 had a specific clinical trial adverse events data 5 base within the clinical trial data base. 6 Q. When you say the clinical trial 7 data base, is that one entire data base for all 8 clinical trial information or are there specific 9 data bases set up for each clinical trial that 10 was performed? 11 A. That's a very complicated 12 question, I'm sure, because we start at some 13 point and we had different systems, and then they 14 have newer systems. But what is attributed to 15 the clinical trial data base really relates to 16 all clinical study information that we have, and 17 it can be in various systems, but people within a 18 given product cluster would have access to that, 19 and there would be systems analysts that are 20 assigned to that. 21 Q. To your knowledge would it be 22 possible to make an inquiry to one source, 23 meaning one data base, or one system, where you 24 could collect information, say, for instance, on Page 374 1 all suicidality related adverse events that 2 occurred in the clinical trials? 3 A. You can make an inquiry, but my 4 sense would be that there would be a lot of 5 manual intervention that would be required on the 6 clinical trial data base side of things, people 7 looking at paper and output and asking questions. 8 It would be much more -- it would be much less 9 sophisticated than what we have with our Drug 10 Experience Network system. 11 Q. When you say looking at manual 12 review of paper, what do you mean, like CRFs, 13 looking at actual clinical report forms? 14 A. It would probably involve that 15 as well. 16 (PLAINTIFFS' EXHIBIT NO. 6 WAS 17 MARKED FOR IDENTIFICATION AND 18 RECEIVED IN EVIDENCE.) 19 Q. Have you had a chance to review 20 Exhibit 6? 21 A. I haven't read it, no. 22 Q. Why don't you go ahead and read 23 it. 24 A. Okay. Page 375 1 Q. Do you recognize Exhibit 6? 2 A. Some of the exhibits what? 3 Q. Do you recognize Exhibit 6? 4 A. Yes. 5 Q. Can you tell me what it is? 6 A. It's our responses that states 7 in the RE line to the audit report that MQA 8 conducted on April 11th. 9 Q. 1990, right? 10 A. Right. 11 Q. Is this the first or second 12 audit that you recall? 13 A. I can't remember now whether 14 this was the first or second one honestly. 15 Q. On the second page of the 16 exhibit, towards the bottom of the second full 17 paragraph or second paragraph, it says that these 18 reports were discussed through page thirty-four 19 in the draft audit report. Do you recall how 20 long the -- pagewise, the actual audit report 21 resulting from this audit was? 22 A. No, I don't. 23 Q. Would you have had a copy of 24 that audit report in your possession at any time? Page 376 1 A. Yes, I would have. 2 Q. Would you have had a copy of 3 that audit report in your file? 4 A. I don't know whether I would 5 have or not. It would depend on where we kept 6 the -- where we had it filed -- or whether I kept 7 it or not. 8 Q. Was there a copy of it in the 9 DEU? 10 A. There certainly would have been 11 at one point in time. We tried not to have lots 12 of these copies floating around, no. 13 Q. Wouldn't it have been important 14 to keep the copy of the MQA's audit report on 15 your department within your department somewhere 16 for reference purposes? 17 A. I don't remember that it would 18 have necessarily have been because we would be 19 meeting with our MQA colleagues on a periodic 20 basis anyway, and our response would be our 21 commitments, and then our commitments we would 22 need to be following up on. And I would have 23 questions of staff as we were pursuing what those 24 commitments were, although they're not outlined Page 377 1 here. 2 Q. Is there a separate document 3 that's not attached to the exhibit that comprises 4 your department's response to the MQA audit? 5 A. Yes, there would have been a 6 response someplace. This looks to me like this 7 is a general response. 8 Q. So when you say this, you mean 9 the exhibit, Exhibit 6? 10 A. Right. 11 Q. Would you have kept a copy of 12 the response in your files? 13 A. I might have. 14 Q. If you did, would you have 15 turned that over to the legal department? 16 A. Not necessarily. If I 17 recognized that it had something to do with 18 Fluoxetine or it was stated on there that it had 19 something to do with Fluoxetine, then I would 20 have. 21 Q. But this exhibit was turned 22 over, was it not, this document was turned over? 23 A. Yes, it looks to me like it was 24 here. Page 378 1 Q. Is there any reason why you 2 would have felt that this document was related to 3 Fluoxetine, but your department's response to the 4 MQA audit was not? 5 A. Say the question again. 6 Q. Sure. Is there any reason why 7 you would have felt it necessary to turn this 8 memo and the attachments to it over to the legal 9 department as responsive to their request for 10 Fluoxetine related documents, and felt that it 11 was not responsive to turn over your company's 12 response to the MQA audit that this refers to? 13 MR. MYERS: Before he answers, let me 14 object to the form only to the extent your 15 question assumes that he would have had the two 16 simultaneously when he turned his files over. 17 But tell her if you know. 18 A. Basically what I would do when 19 I was asked to provide files, I did not, in most 20 cases, go through all those files. I had awful 21 lots of files, and if I saw something that had 22 Fluoxetine on it, some cases I would just pull it 23 out and pass it on. So I would not go through 24 the file in any appreciable detail. And so if it Page 379 1 wound up in there, then it was there. 2 Q. How many files did you have 3 that you turned over? 4 A. I have no idea in terms of how 5 many files that I turned over. I had lots of 6 files on lots of things, I tended to keep an 7 awful lot. 8 Q. The first time that you were 9 asked to turn over documents to the legal 10 department, how long did it take you to gather 11 those documents? 12 A. I can't remember how long that 13 took. 14 Q. More than a day? 15 A. I wouldn't think so. I would 16 have just gone through and I would have looked 17 for anything that would have had Prozac or 18 Fluoxetine on it, and then I would try to think 19 of anyplace where I might have put something that 20 would have stated Fluoxetine, then I would try to 21 go to that specific file. But I did not go 22 through every file that I have, that would have 23 been a very tedious and not very productive task. 24 Q. Do you remember how many boxes Page 380 1 of documents you turned over over the years to 2 the legal department regarding Fluoxetine? 3 A. No. 4 Q. More than one? 5 A. I would be surprised if it was 6 more than one. 7 Q. If you had a copy of your 8 response to the MQA April '90 audit, would you 9 have turned that over to the legal department? 10 A. If it had -- if it was 11 recognized that it had something that stated 12 something about Fluoxetine, then I would have. 13 Otherwise I wouldn't have. 14 Q. Would it be possible to search 15 your files to see if there's a copy of the 16 response and the original audit report somewhere 17 within the DEU or somewhere where you would have 18 access to it at this time? 19 A. It would be possible, I have no 20 idea what we -- I guess what we would find, 21 because I haven't worked in that area for quite 22 some time. 23 Q. Could you make a search for 24 those documents and turn those over to counsel? Page 381 1 MR. MYERS: You have to make a formal 2 request for those, we're not going to turn this 3 into a document production. He doesn't work over 4 there anymore, so just make a request and we'll 5 consider it as we do all of your requests. 6 MS. ZETTLER: I think these documents 7 are clearly nonresponsive to our request for 8 production that we have made in the past, they 9 have not been produced. 10 Q. To your knowledge is there any 11 reason why the MQA audit report or your 12 department response to that report would have 13 been destroyed or thrown away? 14 A. Destroyed or thrown away? I 15 don't know why we would have, no. 16 Q. And that would be true for the 17 other audit that you can't recall that happened 18 before this one? 19 A. Yes, I am sure there's probably 20 information around somewhere, although it 21 certainly wasn't necessary for us to keep a 22 record of all those documents. Those documents 23 would be around someplace, if nowhere else, in 24 MQA, I'm sure probably keeps a copy. Page 382 1 Q. Why wouldn't it be necessary 2 for you to keep those documents? 3 A. Well, the key thing is that we 4 follow up on our recommendations in our response, 5 and that's what I would be working through. The 6 initial observations would not achieve full 7 clarity until we responded to those observations, 8 and then we would say what it is we were going to 9 do if there were some recommendations they would 10 make in order to improve the system. 11 Q. Would MQA follow up with you to 12 make sure that their recommendations had been 13 carried out? 14 A. Yes, they would be back. 15 Q. Did they generally give you a 16 period of time in which to make any changes they 17 felt were necessary? 18 A. Yes. 19 Q. What was your period of time? 20 A. It would depend on what the 21 recommendation of change was. If it were 22 something you could get done fairly quickly, then 23 usually what we would is -- we would make a 24 commitment to say what we were going to do in Page 383 1 what specified period of time. Some things could 2 conceivably take an hour, some things could take 3 weeks or months or longer. 4 Q. Was the change to the DEN two 5 in response to a MQA audit? 6 A. Not as I recall, no. 7 Q. Do you recall any changes that 8 were made with regards to the DEN that were 9 response to either the MQA audits that were 10 performed on the DEN when you were there? 11 A. It seems like we made some 12 procedural changes that were made, I don't 13 remember any -- I don't remember any definitive 14 DEN inhancements that were made, although it does 15 seem that there were some minor ones that were 16 made, but there were none of any major 17 proportions that were made to DEN. 18 Q. When you say DEN enhancements, 19 what do you mean? 20 A. An enhancement might mean that 21 maybe you want to generate an additional report 22 or tabulation to confirm that you're doing what 23 you say you're doing. That might be something. 24 Or there may be -- I do recall that there was -- Page 384 1 we had some authorization that we wanted to 2 strengthen so that people couldn't get 3 information from DEN quite easily. So we had -- 4 seemed like we had a sign-off process that had 5 been strengthened. 6 Q. Why did you want to make it so 7 people couldn't get information from DEN so 8 easily? 9 A. Part of the difficulties that 10 you run into, if someone pulls information out 11 and looks at the data, they may not be able to 12 interpret that data relative to the overall 13 perspective to what's going on, and we wanted to 14 be able to make sure that the appropriate 15 interpretation was applied, and therefore there 16 was a limited audience of people that would be 17 able to pull that information out. 18 Q. So the authorization for 19 entering the system was narrowed to the scope of 20 the authorization? 21 A. The authorization on what? 22 Q. For entering into the system. 23 A. No, I'm not entering -- output. 24 Entering was always pretty tight. Page 385 1 Q. I don't mean entering data 2 into, I mean like getting into the data base to 3 take a look at stuff and ask for information. 4 You narrowed down the scope of the number of 5 people and types of people that could get in 6 there? 7 A. Yes, there was a process where 8 people could go through individuals, maybe the 9 DEN coordinator, to get information, and then 10 they would provide it. But we had some checks 11 and balances we wanted to make sure that were 12 there. 13 Q. Do you remember when that was 14 done? 15 A. I don't recall, no. 16 Q. Was it before or after Doctor 17 Teicher's article came out? 18 A. It would have been irrelevant 19 to Doctor Teicher's article. I do not remember 20 anything that we changed relative to the DEN 21 system that related to the Teicher publication. 22 Q. Okay. But my question is: Did 23 this change or narrow the authorization to use 24 the system, was that done before or after Doctor Page 386 1 Teicher's article came about? 2 A. When did Doctor Teicher's 3 article come out? 4 Q. February of '90. 5 A. This was done in April of '90, 6 so some of the things were done after Doctor 7 Teicher's article, but it didn't have anything to 8 do with Teicher's article, it had to do with this 9 audit, which was independent of that. 10 Q. Do you specifically recall that 11 the authorization for entry into the system or 12 using the system was narrowed down after February 13 of 1990? 14 MR. MYERS: I object to the form only 15 to the extent that I think what he said the 16 authorization was for was to pull out. 17 Q. When I say entering into the 18 system, I don't mean entering data, I mean 19 somebody being able to physically get into the 20 system to either look at information or pull 21 information -- to get information out. 22 MR. MYERS: I think he was talking 23 about people getting information out. 24 A. Anytime I hear the word entry, Page 387 1 I'm thinking -- 2 Q. Let me ask you this: Do you 3 have specific recollection of the authorization 4 or the number of people authorized to get 5 information out of the DEN being narrowed after 6 Doctor Teicher's article came out in February of 7 1990? 8 A. I don't remember that we 9 reduced the number of people who could get 10 access, I do remember they had to go through a 11 different or more complicated sign-off process in 12 order to get the information. 13 Q. So the same number of people 14 could get the information, they just had to go 15 through a different process? 16 A. As I recall, that's right. 17 Q. When did that happen, did that 18 happen before or after Doctor Teicher's article 19 came out in February of 1990? 20 A. If it had to do with this 21 particular MQA audit, it would have been after 22 Doctor Teicher's article because this came out in 23 April of 1990, and you indicated Doctor Teicher's 24 article came out in February of 1990. Page 388 1 Q. Do you recall that happened in 2 response to this particular audit, the one 3 reflected in Exhibit 6? 4 A. It seems to me that the one 5 that I was referring to was in response to this 6 audit, yes. 7 Q. Are you familiar with the SSAI 8 dictionary, Signs, Symptoms and Illnesses? 9 A. Probably very little other than 10 the fact that I know that it is a dictionary. 11 Q. Were you employed at Lilly 12 while you were working in the DEU? 13 A. I don't know whether it was or 14 not. 15 Q. How about the ELECT dictionary, 16 are you familiar with the ELECT dictionary? 17 A. It was a little bit more 18 standard. 19 Q. What do you mean a little bit 20 more standard? 21 A. It seemed like it was closer to 22 the COSTART dictionary, which was what we used. 23 Q. Are you familiar with the ELECT 24 dictionary itself? Page 389 1 A. Not really, I never really had 2 to use it. 3 Q. You are aware that the ELECT 4 dictionary was used at Lilly for a certain period 5 of time, are you not? 6 A. Yes. 7 Q. And you're aware that the ELECT 8 dictionary is a dictionary created by Lilly as 9 opposed to the FDA; correct? 10 A. I couldn't have attested to 11 that, no. 12 Q. Do you know who created the 13 ELECT dictionary? 14 A. No. 15 Q. Are you aware of any changes 16 that were made in the ELECT dictionary while you 17 were in the DEU? 18 A. When I was manager of the DEU, 19 it seemed that there was ongoing review of the 20 dictionaries to continue to update them. And I 21 remember some discussions being held at the 22 meetings in which I was in attendance, although I 23 was not one of the primary participants of that, 24 I just happened to be there. Page 390 1 Q. When you say the dictionaries, 2 what do you mean, was there more than one than 3 just the ELECT? 4 A. Some of the discussions that I 5 remember had to do with some of the various 6 companies trying to work with the FDA in trying 7 to come up with standards that could be used in 8 trying to utilize those standards across the 9 world. So I know there was some harmonization 10 efforts to try and standardize terms across the 11 world by a variety of regulatory agencies and 12 companies. 13 Q. Was this in conjunction with 14 CIOMS? 15 A. CIOMS. I don't think -- well, 16 I don't know, I don't know whether CIOMS was 17 involved with that or not. It seems like WHO was 18 involved with that. The CIOMS organization does 19 tie into WHO, but I'm not sure it wasn't a 20 separate movement or initiative from the CIOM 21 1639 reports. 22 Q. When you say WHO, you mean the 23 World Health Organization? 24 A. That's correct. Page 391 1 Q. Are you aware that the World 2 Health Organization had their own event term 3 dictionary? 4 A. Yes. 5 Q. And was there a problem with 6 that dictionary that was the cause of this 7 attempt to harmonize? 8 A. Well, the issue was that there 9 were differences, and then as you tried to have 10 something reported in one country and try to 11 report it in another country, and if the term has 12 a different meaning over in the other country, 13 that obviously could become an issue. 14 Q. Were you aware that as part of 15 COSTART, the FDA COSTART dictionary, they have a 16 section that translates COSTART terminology to 17 WHO ART terminology? 18 A. I heard something about that, 19 yes. 20 Q. Any other dictionaries that you 21 were talking about when you said that you were 22 aware that there were revisions to the 23 dictionaries? 24 A. We covered SSAI and COSTART and Page 392 1 ELECT. It seems like there might have been 2 another one around, but I can't remember the name 3 of it. 4 Q. Does the Lilly Drug Dictionary 5 ring a bell? 6 A. I think you stated that was the 7 ELECT dictionary. 8 Q. I wanted to make sure that it's 9 not two separate things. 10 A. I don't know. It seems like 11 there was just one other name that I remember, 12 but I remember about a name, but I don't remember 13 what that name was. I've never really been 14 involved with trying to look at harmonizing terms 15 or dealing with those issues. 16 Q. Okay. As far as revisions of 17 the actual ELECT dictionary, do you recall any 18 revisions that were made to that dictionary 19 specifically? 20 A. There was something about 21 surgery, and I don't remember what the issue was 22 on it. 23 Q. Do you recall a change to the 24 ELECT dictionary where the ELECT term injury, Page 393 1 intentional or intentional injury was changed to -- 2 was changed in any way? 3 A. I don't remember that if that 4 was done. 5 Q. How about intentional overdose 6 being changed to overdose? 7 A. I don't remember anything about 8 that. I know there was discussion about 9 overdose, but I couldn't tell you about the 10 substance of that. 11 Q. When was the discussion about 12 overdose done? 13 A. Pardon me? 14 Q. When do you recall this 15 discussion about overdose taking place? 16 A. When? 17 Q. Right. 18 A. It seems to me there was 19 discussion about that when the 1985 regulations 20 were published, as we were trying to achieve 21 clarity with what all those statements meant or -- 22 yes, meant. 23 Q. Who was involved in the 24 revisions or discussion of the revisions Page 394 1 regarding the dictionaries? 2 A. I believe the fellow by the 3 name of Doctor Matsumoto would have been. 4 Q. Is he still with Lilly? 5 A. No, he's retired. 6 Q. Do you know where he lives? 7 A. The last I know, he lived in 8 Indianapolis, but I don't know whether he's still 9 here or not. He was originally from the west 10 coast, and possibly might have moved out there, I 11 don't know. 12 Q. Especially if we had too many 13 days like today. 14 A. Yes, I think he's from Seattle, 15 so that's the way it is there. 16 Q. When did he retire? 17 A. It seems like it was last year. 18 Q. Anybody else that was involved 19 in discussions about the revisions to the 20 dictionary? 21 A. I'm sure there were a number of 22 other people who were involved with it, but his 23 name kind of sticks out as being the primary one, 24 he was our representative that interacted with Page 395 1 the FDA and other companies. 2 Q. How about -- were you finished? 3 A. Yes. 4 Q. How about in-house changes to 5 the ELECT dictionary, who would have been 6 involved in that? 7 A. I don't know who the people 8 would have been involved with it. 9 Q. Clinical research physicians? 10 A. I would assume so. 11 Q. Are you aware that at some 12 point in time, at least with regards to 13 Fluoxetine, Lilly changed from using the ELECT 14 dictionary to using the COSTART dictionary? 15 A. I couldn't relate that it was 16 specific to Fluoxetine, but I was aware that we 17 were making a change in going from ELECT to 18 COSTART, right. 19 Q. When did that take place? 20 A. I don't know. 21 Q. Before you left the DEU? 22 A. My recollection is that there 23 were some steps along the way where some changes 24 were made and there were some other changes that Page 396 1 were made, but I don't remember it just being one 2 major change occurring. And some of that did 3 occur, at least when I was in medical regulatory 4 affairs, I can't remember whether it was when I 5 had immediate responsibility for the DEU or it 6 was after that. 7 Q. When you say that there were 8 some steps along the way, you mean that there 9 were event terms changed in the ELECT dictionary 10 prior to the change to COSTART taking place? 11 A. It seems to me that there were, 12 and it seems that some of those were prompted by 13 some of those discussions with Matsumoto and the 14 people with FDA, and so on, as they were trying 15 to standardize. 16 Q. Do you know if harmonization 17 has ever taken place between various companies 18 and different countries within the FDA with 19 regards to event term reporting? 20 A. Yes, that was the intent with 21 that function to do that. I don't know what the 22 outcome was or what the final conclusions or 23 summaries were. 24 Q. To your knowledge, the portion Page 397 1 of the COSTART dictionary that translate the 2 COSTART terms to the WHO ART terms, was that done 3 in response to this attempt to harmonize? 4 A. I don't know. 5 Q. Let's go back to the 6 subsyndromal syndrome that you were talking about 7 yesterday. Is subsyndromal syndrome a recognized 8 psychiatric or medical condition? 9 MR. MYERS: Well, before he answers I 10 object to the form. That may well call upon him 11 to make a medical opinion or judgment. If he 12 knows as a lay person, tell her. 13 A. I understand that it is 14 something that has been more recently identified 15 by certain thought leaders in the field. 16 Q. Thought leaders in the field -- 17 A. Of psychiatry. 18 Q. Psychiatric field. Is this 19 something that was discovered in relationship to 20 the use of seratonin reuptake or uptake 21 inhibitors? 22 A. I don't know that it was or it 23 wasn't. It was my understanding that it was some 24 sort of a diagnostic, what's the term, diagnostic Page 398 1 understanding as it relates to depression, but I 2 couldn't tell you what the specifics are on that. 3 Q. To your knowledge, was there 4 ever a study contemplated at Lilly to look at the 5 increase of deterioration of condition of people 6 suffering from depression who are being treated 7 with antidepressants generally? 8 A. I'm sorry, to see if patients 9 who were depressed got worse if they were treated 10 with antidepressants? 11 Q. Or to study the incidence of 12 people who became worse while they were being 13 treated with antidepressants. 14 A. I'm not aware of that, no. 15 Q. The subsyndromal syndrome, is 16 that related to seratonin levels in any respect? 17 A. I don't know. 18 Q. Is that study that you talked 19 about, the multi-center study, is that supposed 20 to be an inpatient or outpatient study? 21 A. I don't know. 22 Q. Does the study involve movement 23 disorders at all, like tardive dyskenisia or 24 anything like that? Page 399 1 A. I don't know. 2 Q. Are you familiar with tardive 3 dyskenisia? 4 A. I've heard the term, I couldn't 5 give you a definition for it. 6 Q. Have you heard the term 7 akathisia? 8 A. What's the term? 9 Q. Akathisia. 10 A. I can't relate to it, no. How 11 do you spell it? 12 Q. I'm not sure, 13 A-K-A-T-H-A-S-I-A, I believe. 14 A. I've seen it written, but I 15 don't know what it is. 16 Q. Have you ever heard the term 17 seratonin syndrome? 18 A. No. 19 Q. Have you ever heard of Doctor 20 Jonathan Cole? 21 A. Jonathan -- 22 Q. Cole, C-O-L-E. 23 A. No. 24 Q. How about Doctor Janet Page 400 1 Amsterdam? 2 A. No. 3 Q. I forgot what you told Paul 4 yesterday, is this study, the subsyndromal 5 syndrome study, being conducted now? 6 A. I don't believe it's started 7 yet, no. 8 Q. Do you know what projected date 9 that they have for starting the study is? 10 A. It was projected to start 11 sometime -- the intent was to start before the 12 end of 1993. 13 Q. Have you ever heard of Doctor 14 Ivan Miller? 15 A. No. 16 Q. How about Doctor Jan Fawcett? 17 A. Jan Fawcett, no. 18 Q. How about Louis Fabre? 19 A. I've heard that name. 20 Q. Is Doctor Fabre one of the 21 investigators to study this subsyndromal 22 syndrome? 23 A. No. 24 Q. To your knowledge, are the Page 401 1 investigators that Lilly is contemplating using 2 on those clinical trials for the subsyndromal 3 syndrome, psychiatrists? 4 A. I believe that they are, yes. 5 Q. How is it that you came to 6 learn about this subsyndromal syndrome study? 7 A. We had a lot of discussion 8 about the budget for the study, and that's how I 9 got involved with it. 10 Q. And that's in your present 11 position, you're involved in those discussions? 12 A. Correct. 13 Q. Do you recall a concern or a 14 notation of an increase in frequency of incidents 15 of tardive dyskinesia or other movement disorders 16 associated with the use of Fluoxetine? 17 A. No. 18 Q. Were you ever charged with 19 gathering data on incidents of tardive dyskinesia 20 or other movement disorders related to 21 Fluoxetine? 22 A. No. 23 Q. How about your department, were 24 they charged with gathering that information? Page 402 1 A. I don't know, I wouldn't be 2 aware of everything that would be requested of 3 them from a research physician. We tried not to 4 have layers of management get in the way of 5 trying to get responses taken care of when 6 questions were asked. 7 (PLAINTIFFS' EXHIBIT NO. 7 WAS 8 MARKED FOR IDENTIFICATION AND 9 RECEIVED IN EVIDENCE.) 10 Q. Have you had a chance to look 11 at Exhibit 7? 12 A. Yes. 13 Q. Can you tell me what it is? 14 A. The title of it is tardive 15 dyskinesia reports. 16 Q. But as far as besides the title 17 of it, what is this document? 18 A. It just says it's a summary of 19 the case statuses provided by one of the people 20 in the drug epidemiology unit. 21 Q. Do you remember Doctor Thompson 22 requesting this information? 23 A. I don't, no. 24 Q. Do you remember why this Page 403 1 information was provided to Doctor Thompson 2 besides the fact that he requested it? 3 A. No, I don't. 4 Q. Have you ever dealt with any 5 outside consultants regarding tardive dyskinesia 6 or movement disorders? 7 A. No, I have not. 8 Q. Have you ever dealt with any 9 outside consultants with regards to any adverse 10 events related to Fluoxetine? 11 A. Outside consultants as relates 12 to Fluoxetine, no. 13 Q. Do you recall other requests 14 for information, such as the request that's in 15 Exhibit 7, with regards to any other adverse 16 events related to Fluoxetine? 17 A. Do I recall any other requests -- 18 say it again. 19 Q. Do you recall any other 20 requests for compile of information such as the 21 one done on tardive dyskinesia in Exhibit 7? 22 A. No, not specifically, no. 23 Q. How about generally? 24 A. There probably were requests Page 404 1 that were made, but I couldn't tell you what they 2 were. If I got a request for something, I would 3 very quickly give it to one of my staff who had 4 responsibility for the given area, and I would 5 ask them to go ahead and handle it. And in this 6 case, this one went out under my name, probably 7 because the person who was providing it had not 8 been there for very long, so I probably asked her 9 to just give it to me and then I passed it on to 10 Doctor Thompson. 11 MR. MYERS: So the record is clear, in 12 that stack of paper is more than one document. 13 It appears to be all on the same general subject 14 matter, I'll grant you that, but it's not the 15 same document, and I don't want there to be any 16 confusion as to what the witness is testifying 17 about. 18 MS. ZETTLER: There's two copies of the 19 same memo with the attachments, and there's two 20 other E-mails, one written by Mister Noone and 21 one written by Doctor Kotsanos. 22 MR. MYERS: Yes, I'm not suggesting 23 it's not about the same thing, it's just more 24 than one thing. It's a composite exhibit. Page 405 1 MS. ZETTLER: You're just too smart for 2 me, Larry. 3 Q. If you could turn to page 1971, 4 Pz 1971 405. 5 A. Right. 6 Q. It looks like an E-mail from 7 you to Leigh Thompson dated August 17, 1990? 8 A. Right. 9 Q. The first paragraph kind of 10 alludes to a sense of urgency in the gathering of 11 this information; is that correct? 12 A. Yes. 13 Q. Do you remember why it was 14 urgent or why you stepped up the pressure as you 15 stated in the memo in gathering the TD 16 information? 17 A. I would assume Doctor Thompson 18 was stepping up the pressure for whatever reason, 19 and I therefore was responding in kind. It was 20 typical that Doctor Thompson would make the 21 request, and Doctor Talbott also would be pushing 22 us to get some response back fairly quickly. 23 Q. Do you recall an increased 24 frequency report that was generated on tardive Page 406 1 dyskinesia at any time? 2 A. I'm not aware of it. There may 3 well have been, but I'm not aware of it. 4 Q. The second paragraph of the 5 memo, it says the staff also are aware that if 6 they can gather better information by site visit, 7 that this approach should be utilized. Was that 8 typical with regards to gathering information on 9 adverse events that previously existed in the 10 data base? 11 A. Yes, I think it's, as this 12 states here, if they can get better information 13 by site visit, that that approach would be 14 utilized, and we did utilize that in other 15 occasions as well. 16 Q. What other occasions? 17 A. Well, it was for the most part, 18 as I can recall, if we had a -- I'm trying to 19 think of a specific example, but one is not 20 coming to mind. If we had some information that 21 came in that we were not sure of the background 22 and whether the event related to the diagnosis of 23 the drug, and there were, as I suggested 24 yesterday, either autopsy reports or other Page 407 1 information at the site, then we would send 2 people out to get that, in which case we would 3 use not only our own people but other people in 4 the field to gather that. They would just drop 5 what they were doing and do that. As I read this 6 memo now, I do remember something about this at 7 this point. 8 Q. What do you remember? 9 A. I remember that it was 10 something that we had -- apparently there had 11 been some events that had taken place with that, 12 and Doctor Thompson, as the head medical person, 13 was wanting folks to get more information so we 14 could get a better understanding of it, so that's 15 why we were putting together an all out effort to 16 gather of information that needed to be brought 17 in. 18 Q. When you say something was 19 happening with these events, what do you mean, 20 increased frequency? 21 A. If you have -- and I don't -- 22 let's say you had -- you had not had any tardive 23 dyskinesia before, and all of a sudden you had 24 some of it showing up and you didn't know whether Page 408 1 it related to the drug or not, we would put out a 2 strong effort at that point to try and pin down 3 what the issue was, was it indeed related to the 4 drug. And, therefore, we might have a need to 5 gather more information. It certainly would have 6 a much different tone than if you had something 7 that you had seen reported before and you're 8 aware that it relates to the drug, you wouldn't 9 have a need to push together further information, 10 but if it's something new and novel, then from a 11 medical standpoint, if not from a regulatory 12 standpoint, you have an obligation to try and 13 find that out. 14 Q. How about incidents of 15 intentional injury to others by people who were 16 using Fluoxetine, do you ever recall a gathering 17 of information such as the one done as reflected 18 in Exhibit 7 done with that issue? 19 A. I don't remember that, no. 20 Q. Do you remember an issue 21 regarding an increase in the incidence of 22 overdose on Fluoxetine? 23 MR. MYERS: When you say an incident, 24 where he was asked to make the same kind of Page 409 1 inquiry that he made for Exhibit 7? 2 MS. ZETTLER: No, where there was an 3 increase of the frequency of adverse events 4 related the to overdose of Fluoxetine that were 5 reported. 6 A. I don't remember that, no. 7 Q. Do you remember the frequency 8 or the incidents of overdose of people using 9 Fluoxetine, and I don't mean just using 10 Fluoxetine in the overdose, being an issue with 11 regards to Prozac? 12 A. I don't remember that being an 13 issue, no. 14 Q. Do you recall marketing 15 sessions or telesessions that were run with 16 regards to Fluoxetine with psychiatrists and 17 interns, like focus groups, things of that 18 nature? 19 A. I remember something about 20 telemarketing sessions, that those were done. It 21 was a common occurrence in marketing to do that 22 with some of the newer products that the company 23 had, whether it was Prozac or other products. 24 Q. Adverse events that were talked Page 410 1 about by participants of those focus groups, 2 would those then be reported as spontaneous 3 events through the DEN to the FDA? 4 A. Yes, for people who became 5 aware of it, they had an obligation to provide 6 that information in-house. 7 Q. To your knowledge, were those 8 focus groups, any of those focus groups or 9 telemarketing sessions, were they video taped or 10 audio taped? 11 A. I recall that some -- they were 12 audio taped from what I recall. I don't remember 13 any video taped, but I do remember some were 14 audio taped. 15 Q. Do you know if those audio 16 tapes are still in the possession of employees at 17 Lilly or ever were in the possession of the 18 employees at Lilly? 19 A. Were they or are they in 20 possession of Lilly employees? 21 Q. Right. 22 A. They have been, yes. 23 Q. Do you know if they still are 24 in the possession of employees at Lilly? Page 411 1 A. I can't answer that, no. 2 Q. What department was responsible 3 for conducting the focus groups? 4 A. As I recall, the marketing 5 component was responsible for doing those. 6 Q. To your knowledge, were any 7 focus groups specifically conducted to 8 investigate the incidence of any adverse events 9 with regards to the use of Fluoxetine? 10 A. Not that I'm aware of, no. 11 Marketing would typically -- that wouldn't be 12 their focus. 13 Q. What was the purpose of 14 conducting the focus groups? 15 A. I would have to say that relate 16 to this, generally, to my understanding of focus 17 groups, based upon my time back in marketing, 18 what I guess I think I still know about it, the 19 intent was to understand why practitioners used 20 given medications, what was the clinical piece 21 that drove them to use a given drug, what things 22 were they satisfied with, what things were they 23 not satisfied with, and then marketing would then 24 attempt to understand that and then attempt to Page 412 1 deal with that from a strategic or message 2 standpoint. 3 Q. Have you ever heard of an 4 incident at Lilly where a clinical trial was 5 conducted specifically in response to complaints 6 made by practitioners in the focus groups 7 regarding the use of Fluoxetine? 8 A. I'm not aware of that. That's 9 not saying it didn't happen, but I'm not aware of 10 that. 11 Q. My understanding is 1639s that 12 were sent to the FDA regarding spontaneous 13 reports or serious clinical trial reports were 14 computer printouts from the DEU; correct? 15 MR. MYERS: DEN? 16 A. DEN system, yes. 17 Q. If a 1639 from the DEN was sent 18 to the FDA, could that report be then deleted 19 from the DEN if it was found to be a duplicate, 20 say? 21 A. Yes. 22 Q. What would you then do with the 23 FDA to notify them that you had made duplicate 24 reports? Page 413 1 A. I don't remember that 2 procedure. As I recall, I remember we did send 3 them a notice that that report had been a 4 duplicate of another report. 5 Q. To your knowledge, was there 6 ever a hotline set up outside of Eli Lilly to 7 handle adverse event reports on Lilly drugs? 8 A. What do you mean by hotline set 9 up outside of Lilly? 10 Q. Was there ever an entity that 11 was chosen or asked to act as a hotline for 12 adverse event calls related to any Lilly drugs? 13 MR. MYERS: An entity outside Lilly? 14 MS. ZETTLER: Right. 15 A. I can't remember any. 16 Q. How about an office outside of 17 Lilly in Indianapolis? 18 A. A Lilly office? 19 Q. Yes. 20 A. Well, it depends on how we 21 define it. If it was something that occurred in 22 an overseas affiliate, I'm not aware of what 23 their procedures are, but I'm sure that they 24 would have to have people contact their affiliate Page 414 1 in order to meet our corporate rules about 2 reporting events. They had forty-eight hours to 3 get information to us from the time that they 4 were aware of it overseas. 5 Q. Okay. Have you ever heard of a 6 person by the last name of Kulig, K-U-L-I-G? 7 A. K-U-L-I-G. What's the first 8 name? 9 Q. I don't know. 10 A. The name sounds familiar, but 11 I'm not tracking who it might be. 12 Q. How about Harry Hubble? 13 A. Yes, I know Harry Hubble. 14 Q. Who is Harry Hubble? 15 A. Harry is an attorney, 16 regulatory attorney at Lilly. 17 Q. Was he at the Indianapolis 18 office? 19 A. Yes. 20 (PLAINTIFFS' EXHIBIT NO. 8 WAS 21 MARKED FOR IDENTIFICATION AND 22 RECEIVED IN EVIDENCE.) 23 Q. Have you had a chance to review 24 Exhibit 8? Page 415 1 A. Yes. 2 Q. Do you recognize the exhibit? 3 A. Roughly, yes. 4 Q. Can you tell me what it is? 5 A. I can't see, the heading has 6 been obviously blacked out. This appears to me 7 to be some information that we may have sent to 8 the Rocky Mountain Poison Control Center. 9 Q. That's in Denver, I believe? 10 A. I think that's right, yes. 11 MR. MYERS: Somewhere in the Rocky 12 Mountains. 13 A. I was out there once, and I 14 think that's where it was, was in Denver. 15 Q. Okay. The third paragraph 16 talks about calls being forwarded out there. 17 What did you mean by that? 18 A. We had an arrangement with them 19 that if someone called in that had an overdose, 20 that regardless of what the Lilly product it was, 21 that it would go out to them and they were 22 experts in treating overdose, we were not experts 23 in treating overdose. And typically, when people 24 overdose, they tend to overdose on several Page 416 1 products, and some might be ours, and they might 2 also be other companies' products as well. In 3 order to effectively treat those patients in an 4 appropriate time frame, it was really felt that 5 the expertise did not reside at our company 6 because we did not have the knowledge of drug 7 interactions and incompatabilities and so on, 8 that we really needed to try to look at a way of 9 having experts in the field do that. So with 10 those kinds of calls that we got, those would 11 automatically be forwarded out to them, and they 12 would deal with the emergency room or whoever 13 else might have called to make sure the patients 14 were well taken care of. 15 While they were doing that, if 16 indeed there was something that related to a 17 Lilly product where an adverse was taking place, 18 then they had to provide that information back to 19 us, as I recall it was by fax, so that we could 20 go ahead and have that information reported to 21 the Food and Drug Administration. 22 Q. How fast was the turn around on 23 the call forwarding? 24 A. I don't remember what the exact Page 417 1 time was, but they were instructed that we had to 2 be able to meet our fifteen-day deadlines. I do 3 not recall that we ever had an issue with that. 4 Q. But I'm talking about the 5 actual calls to the Rocky Mountain Poison Center. 6 How fast was the turn around on your forwarding 7 of calls regarding overdose? 8 A. They just automatically -- they 9 would come in to us, and then we would -- as I 10 recall I used to have a sticker on my phone when 11 I was over in that area, and if I would have 12 happened to have received a call, which I seldom 13 would have ever gotten it, but then I would have 14 just transferred it just like I would transfer a 15 call inside, we had a special hookup, so it was 16 just like transferring a call inside our own 17 organization. 18 Q. Why did Lilly and the Rocky 19 Mountain Poison Center wait until January of 1991 20 to come up with this agreement? 21 A. As far as I know, this was very 22 innovative in the industry, I don't know if 23 anyone else was doing this type of thing. 24 Historically, if you had an overdose, the Page 418 1 companies would do their best to try and take 2 care of it or maybe talk to an emergency room, 3 let's say, if they called, and then refer them to 4 the appropriate people. But by doing it this 5 way, it was -- in real time you could 6 automatically do that -- 7 Q. Did it have anything to do -- 8 A. -- so I don't know -- go ahead. 9 Q. I'm sorry, I didn't mean to cut 10 you off. 11 A. This one had to do specifically 12 with Fluoxetine and the MAOI, so I don't remember 13 what the specifics were on that, I can't remember 14 now whether that was what prompted us to begin 15 doing that or whether this was a secondary 16 activity that was taking place after we had set 17 up the contract with the Rocky Mountain Poison 18 Control Center. 19 Q. But to your knowledge or 20 memory, there was an agreement between Lilly and 21 the Rocky Mountain Poison Control Center where 22 overdoses on Lilly drugs would be referred to 23 Rocky Mountain? 24 A. Overdose calls that we received Page 419 1 would be referred to Rocky Mountain. Typically 2 you would expect that we were going to get the 3 ones on Lilly calls, but as soon as we knew it 4 was an overdose and had to do with the patient 5 treatment, we wanted to get it to them so they 6 could deal with the patient. 7 Q. Did this have anything to do 8 with an increased frequency of reports of 9 overdoses on Lilly drugs? 10 A. I don't recall that it did. I 11 just remember -- pardon me? 12 Q. Go ahead, I'm sorry. 13 A. That's all right. 14 Q. Who requested that this 15 association between Lilly and Rocky Mountain be 16 set up? 17 A. I believe it was Doctor 18 Thompson. 19 Q. Leigh Thompson? 20 A. Yes. 21 Q. So it was felt that there 22 weren't people with sufficient expertise in 23 overdoses to handle the overdose calls that came 24 in; correct? Page 420 1 A. That's correct, because of the 2 reasons I stated before. Typically patients are 3 on multiple drugs, across multiple countries, and 4 for us to have understanding of drugs with other 5 companies would have been a stretch. 6 Q. With regards to Lilly's own 7 drugs, obviously people at Lilly would have 8 expertise in those areas, wouldn't they, with 9 regards to those drugs? 10 A. I would still say that the real 11 expertise in dealing with overdose situations 12 would really be more with the Rocky Mountain 13 Poison Control Center, and part of what we did 14 was provide them with background on our products 15 as well to make sure they were current and 16 up-to-date. 17 Q. You had a number of 18 psychiatrists that were on staff, M.D. 19 psychiatrists that were on staff, working on at 20 least psychotropic drugs at Lilly; correct? 21 A. That's correct. 22 Q. Is it your testimony that these 23 ladies and gentlemen did not have the expertise 24 necessary with regards to drug interactions or Page 421 1 the affect of any particular drug that they could 2 handle an emergency overdose situation? 3 A. It would be my testimony that 4 they did not have the expertise of Rocky Mountain 5 Poison Control Center, which dealt with these 6 things on an ongoing basis across drugs, across 7 many companies. 8 Q. Prior to the the association 9 between Lilly and the Rocky Mountain Poison 10 Control Center, how were overdose calls handled 11 at Lilly? 12 A. It would have been handled on 13 an individual basis by the given physician. 14 Q. The research physician? 15 A. Right, whoever would have 16 received the call. 17 Q. Okay. Somebody who receives 18 the call or would the calls be forwarded to, say, 19 if it was somebody overdosing with Fluoxetine, 20 would the call be forwarded to a research 21 physician who was working with Fluoxetine? 22 A. I would assume that would 23 probably be the case, yes. 24 Q. To your knowledge, is this Page 422 1 association between Lilly and Rocky Mountain 2 still in existence? 3 A. I don't know. 4 Q. Was it in existence when you 5 left the DEU? 6 A. Yes. 7 Q. On the second page at the top, 8 it says letter slash Kulig. Does that refresh 9 your recollection? 10 A. Yes, that's where I thought I 11 had heard the name Kulig, was the person that was 12 at the Rocky Mountain Poison Control Center. 13 Q. Is it a he or she? 14 A. I think it's a he, I believe 15 it's Ken. 16 Q. Is this letter that you wrote, 17 the first page of Exhibit 8, is that to Doctor -- 18 is it Doctor or Mister Kulig? 19 A. As I recall, Doctor Kulig. 20 Q. Is this letter to Doctor Kulig? 21 A. It's addressed to someone at 22 Rocky Mountain Poison Control Center, so if it's 23 not addressed to Doctor Kulig -- it appears to be 24 based upon the second page, but if it's not, it's Page 423 1 to one of Doctor Kulig's colleagues. 2 Q. To your knowledge, is the Rocky 3 Mountain Poison Control Center involved in the 4 subsyndromal syndrome study? 5 A. No. 6 Q. Is that the only hotline that 7 you're aware of at Lilly or is there any other 8 hotline at Lilly with regards to adverse event 9 reporting? 10 A. The term hotline refers to also -- 11 my connotation of the term hotline would have 12 referred to the hotline that we have in the drug 13 epidemiology unit. 14 Q. That's the line that the -- is 15 that anybody can call in or is that specific to 16 the Lilly sales force? 17 A. That number is the one that the 18 sales reps can call into, it's also one that if 19 it goes to the operator, the corporate operator, 20 then it goes down there as well. 21 Q. So if a doctor calls in the 22 general Lilly number and the operator ascertains 23 that it's an adverse event report, she would 24 transfer it to the hotline? Page 424 1 A. I think it would probably be 2 better to characterize that as a hotline function 3 as opposed to a hotline number. We refer to that 4 group as a hotline group, so they were taking all 5 the calls that were coming in that related to 6 adverse events. 7 Q. Have you ever heard the term 8 PRIS, P-R-I-S? 9 A. Yes. 10 Q. What is PRIS? 11 A. Periodic Reporting Information 12 System, something of that nature. 13 Q. Is that a Lilly item or is that 14 something outside Lilly? 15 A. That's a Lilly term. 16 Q. Okay. What does it represent, 17 is it a data base? 18 A. It represents the data and 19 output concerning adverse event information that 20 is run at the time of the periodic reports. 21 Q. Okay. Those periodic reports 22 we were talking about earlier, are quarterly or 23 annual spontaneous adverse event reports? 24 A. Yes. Page 425 1 Q. Have you ever heard of an FD 2 thirty-five hundred form, FDA thirty-five hundred 3 form? 4 A. FD thirty-five hundred. 5 Q. With regards to reporting of 6 adverse events. 7 A. That was not -- it's not -- I'm 8 not applying any definition to it, no. 9 Q. Have you ever talked with any 10 clinical investigators outside of Lilly? 11 A. Yes. 12 Q. In what context? 13 A. You're referring to 14 investigators that we would enlist to do studies? 15 Q. Right. 16 A. I have talked to them with the 17 clinical research coordinators as we have gone 18 out and done what I would call site management. 19 Also in going out to determine if an investigator 20 might be qualified to do a Lilly study. 21 Q. Is that when you were in your 22 function in the DEU or is that in your present 23 function? 24 A. In my present function. Page 426 1 Q. Have you ever talked to 2 potential Fluoxetine clinical investigators in 3 your present function? 4 A. I do remember meeting one that 5 I would consider as a potential investigator for 6 Fluoxetine, although that was not why we were 7 there, it had to do with another study. But if 8 we would have the right study or if we had a 9 study, then I would say that person could have 10 been one. 11 Q. Have you ever talked to Doctor 12 Martin Teicher? 13 A. No, not that I can remember, at 14 least. 15 Q. Was there an article published 16 related to the DEN system and its operation? 17 A. Yes, there has been. 18 Q. When was that article 19 published? 20 A. I don't know, it seemed like 21 there might have been more than one, and it 22 seemed that one was published maybe after I left 23 because I think we had one of our people that 24 worked in the area had their name on the article. Page 427 1 Q. Do you remember who that was? 2 A. Pearson, Huddleston -- I'm not 3 sure who the person might have been. 4 Q. Jeff Powell? 5 A. Possibly. 6 Q. Donna Pearson? 7 A. Possibly. 8 Q. Laura Fludzinski? 9 A. I wouldn't think Laura, because 10 I don't think -- Laura never worked in the drug 11 epidemiology unit. 12 Q. Who else was listed as an 13 author on that article? 14 A. I would assume that Doctor 15 Talbott would have been. 16 Q. Anybody else that you remember? 17 A. I say the article one time, but 18 I can't remember now who the people were. 19 Q. Do you remember -- how about 20 Janet Potvin, was she listed on the article? 21 A. I would be surprised if she 22 were because she did not work in the drug 23 epidemiology unit. 24 Q. What was the subject of the Page 428 1 article? 2 A. It was a summary of how we went 3 about collecting adverse events. I think it was 4 felt, with some pride, that we had the best 5 adverse event collection systems in the industry, 6 at least at that time. 7 Q. Was this something that was 8 published after the FDA audit? 9 A. No, this would have been 10 published before that time. 11 Q. Do you think that the 12 publication of that article prompted the FDA 13 audit? 14 A. I don't think so. 15 Q. And this is the article that 16 you believe was published since you've left the 17 DEU; correct? 18 A. Yes. I think -- it seems to me 19 that there were a couple of articles that had 20 been out there. 21 Q. How about the other article, 22 was it published before or after you left the 23 DEU? 24 A. It seems like it might have Page 429 1 been published maybe shortly either before I came 2 in or at least it had been -- it seems like it 3 might have been before I came in. But the timing 4 might have been such that it may well have come 5 out after I was in there, but I don't remember 6 the details being collected to deal with that. 7 Q. Do you remember where either 8 one of the articles were published, which journal 9 or publication? 10 A. No, I don't. 11 Q. Was Doctor Talbott listed as an 12 author on the other article? 13 A. I think he was on both of them, 14 yes. 15 Q. What is your understanding of a 16 drug company's relationship with the Food and 17 Drug Administration? 18 A. What's the relationship -- 19 could you help me to understand what you mean by 20 that? 21 Q. Well, FDA is a regulatory 22 entity; correct? 23 A. Right. 24 Q. And they're charged with Page 430 1 regulating the drug companies in the manufacture 2 and sale and marketing of drugs; correct? 3 A. Correct. 4 Q. What is your understanding of 5 the tenor of the relationship between Lilly and 6 the FDA? 7 A. I think the relationship is 8 positive. 9 Q. How would you feel about an Eli 10 Lilly employee calling an FDA employee at 6:15 in 11 the morning? 12 A. That could be fine. 13 Q. Have you ever heard of that 14 happening at Lilly? 15 A. I could think of it happening 16 relative to a three-day report. 17 Q. Okay. How about -- 18 A. Could be me. I get in fairly 19 early myself, so if I knew that they had someone 20 up there and I had a question on an adverse event 21 report, I could call them. 22 Q. Have you ever called the FDA 23 that early in the morning? 24 A. I can't say that I have, I've Page 431 1 certainly talked to them. 2 Q. To your knowledge has Lilly 3 ever hired employees or former employees of the 4 FDA? 5 A. Yes. 6 Q. Can you tell me who? 7 A. Doctor Talbott was a former 8 employee of the FDA. 9 Q. Anybody else? 10 A. That's the only one that comes 11 to mind. 12 Q. How about Leigh Thompson, was 13 he with the FDA? 14 A. I don't think so. 15 Q. Do you know what Doctor 16 Thompson's background was before coming to Lilly? 17 A. He has a fairly extensive 18 background, I know he was at the Cleveland -- as 19 I recall, at the Cleveland Clinic, he's been at 20 John's Hopkins. 21 Q. Is he a psychiatrist? 22 A. I don't believe so. 23 Q. Do you know how long he's been 24 with Lilly? Page 432 1 A. Oh, since about, I want to say, 2 somewhere around 1982, in that ballpark. 3 Q. Do you know if Doctor Thompson 4 conducted clinical trials on Fluoxetine for Lilly 5 prior to coming to Lilly? 6 A. I don't know. 7 Q. How about Doctor Talbott? 8 A. No, he would not, he's not an 9 M.D. 10 Q. How about Doctor Tollefson? 11 A. Doctor Tollefson may have. 12 Q. Have you ever heard of the drug 13 Axid, A-X-I-D? 14 A. Yes. 15 Q. Can you tell me what Axid is? 16 A. It's a drug that Lilly makes 17 that's used for treatment of ulcer related 18 conditions. 19 Q. How about Nizatidin, 20 N-I-Z-A-T-I-D-I-N? 21 A. That's the generic name for 22 Axid. 23 Q. Pergolide? 24 A. Pergolide is a Lilly product, Page 433 1 Pergolide Mesylate. 2 Q. What's that for? 3 A. Treatment of Parkinsonism. 4 Q. How about Navilane, 5 N-A-V-I-L-O-N-E or L-A-N-E? 6 A. That was a Lilly -- is or was a 7 Lilly product. 8 Q. What is that for? 9 A. As I recall, testing my memory, 10 but I think it had to do with people that were on 11 oncolytics that were severely nauseated, and 12 Navilane helped to keep them from tossing their 13 cookies. 14 Q. You said oncolytics -- cancer 15 drugs? 16 A. Yes. 17 Q. Penbutolol, 18 P-E-N-B-U-L-O-T-O-L? 19 A. That was a cardiovascular drug 20 that I believe we got approval for, but decided 21 not to market. 22 Q. I'm a little confused on where 23 possibly reasonably related comes in. Is that 24 something that's exclusive to clinical trial Page 434 1 reports or is that something that's taken into 2 consideration as far as reporting to the FDA with 3 spontaneous adverse events also. 4 A. It isn't taken into 5 consideration with spontaneous events, and the 6 reason being is that the FDA really didn't want 7 companies making that decision, they preferred to 8 make that decision themselves to determine 9 whether something might be related to the drug or 10 not. 11 Q. Okay. 12 A. So, therefore, you can wind up 13 with some strange things going in conceivably to 14 the FDA on a drug. If somebody gets run over by 15 a car, that's a serious event, and it's 16 unexpected. That conceivably could go in. 17 Q. So it's your testimony that the 18 FDA, as far as spontaneous reports, at least of 19 adverse events, reserves the right to make a 20 determination as to whether or not there's a 21 possible causal relationship between the adverse 22 event and the drug? 23 A. They have the right to 24 certainly do that. What one would hope would be Page 435 1 that if you understood that, you would obviously 2 make that decision yourself before they would. 3 Q. Have you ever seen a printout 4 of any information from the FDA's spontaneous 5 reporting system? 6 A. A printout of -- what kind of 7 printout? 8 Q. Are you aware that the FDA will 9 provide, under the freedom of information act 10 request, a data base or disks of information 11 related to adverse events reported to it on any 12 particular drug? 13 A. Yes, I am. 14 Q. Okay. Have you ever seen a 15 printout of that information contained on those 16 disks for Fluoxetine? 17 A. I can't say that it was 18 Fluoxetine, I do remember seeing some of that 19 information, though. 20 Q. Are you aware that part of that 21 information relates to whether or not a drug is 22 suspected to be causally related to a given 23 adverse event? 24 A. I didn't remember that being on Page 436 1 there, no. 2 Q. Have you ever heard the word 3 suspect with regards to the SRS? 4 A. I've heard the term used, but I 5 couldn't tell you under what connotation. 6 Q. To your knowledge has Lilly 7 ever requested or received from the FDA a copy of 8 their SRS data base for adverse events related to 9 Fluoxetine? 10 A. I believe that we have. 11 Q. Why would you order something 12 like that? 13 A. In order for us to understand 14 that if there were other things that were 15 reported to the agency that we were not aware, 16 that were not reported by us, a reporter can call 17 directly to the FDA. And most of the reports are 18 reported by the companies, but certainly some 19 things can be reported directly to them, and that 20 would help us to gain a better medical clinical 21 understanding if there was something out there 22 that was different than what we had in our data 23 base. 24 Q. Is it your understanding that Page 437 1 the FDA has taken a position that only a small 2 percentage of adverse events that actually occur 3 related to any given drug are ultimately 4 reported? 5 A. Yes. 6 Q. Do you take that into 7 consideration with regards to the increased 8 frequency reports, things of that nature? 9 A. Yes, and -- but if you're -- I 10 guess how I would answer that is to say that 11 you're comparing one period to the next period to 12 the next period as you move on down the line, 13 therefore if, let's say, only ten percent of all 14 reports are being made, you've got ten percent in 15 that period, ten percent here, ten percent there. 16 So as long as that stays fairly constant, then if 17 the numerator changes and the denominator 18 doesn't, then you're going to prompt an increased 19 frequency. 20 Q. So you kind of go in on the 21 assumption that say that there's ten reports, 22 it's really another number higher than ten, 23 across the board? 24 A. If there's ten reports, what Page 438 1 now? 2 Q. Say, for instance -- I mean 3 I've read different figures, anywhere from one in 4 ten, only one in ten adverse events get reported, 5 to only one in twenty at various times. So let's 6 just take one in ten. 7 A. Right. 8 Q. Is it your testimony that Lilly 9 assumes, say, that there's only one report of a 10 rash, that there are probably another nine out 11 there that haven't been reported? 12 A. I can't say -- 13 MR. MYERS: I object to the form. When 14 you say another nine, you mean nine events and 15 not nine reports? 16 MS. ZETTLER: Right. 17 MR. MYERS: You said report in the last 18 question. 19 MS. ZETTLER: Okay. 20 A. I would say that's -- I don't 21 know what the -- I really don't know what the 22 overall percentage that we hear about is of the 23 total number that occur, I have heard agency 24 people think it's somewhere in that ballpark. Page 439 1 Our initial assumption going in would be that the 2 reporting rate would generally not change from 3 period to period unless -- but we would focus on 4 that as well. In other words, if you have a new 5 drug that's introduced, the belief is that you 6 have a higher reporting rate on that drug early 7 in the process because it's new. Also you have 8 sales reps that are detailing that drug. Whereas 9 drugs that have been out there, no one is talking 10 about or there's no one to hear about those, so 11 drugs that have been on the market for years 12 probably have less of a reporting rate than newer 13 drugs do. 14 Q. To your understanding is that 15 part of the reason for the higher number of 16 required reports of increased frequency, say, 17 quarterly reports within the first three years 18 the drug is on the market as opposed to the 19 yearly reports after the first three years? 20 A. Parts of what you're looking at 21 in the first three years, if you're going to 22 uncover something that's different about the 23 drug, you're probably going to uncover it then 24 assuming that it has a lot of usage. A drug that Page 440 1 doesn't have a lot of usage maybe it will take 2 you a lot longer. But if a drug has a lot of 3 usage, you ought to be able to pick up the 4 majority of that in the first three years. 5 Q. Would you agree that Fluoxetine 6 had a lot of usage in the first three years it 7 was on the market? 8 A. Yes. 9 Q. I just want to get an 10 understanding of how the percentages -- I don't 11 mean to try to lock you into certain percentage 12 of unrecorded adverse events, okay, but I'm just 13 trying to get an idea of how that works within 14 the increased frequency realm at Lilly. But 15 let's just, for simplification sake, let's just 16 say only one in ten adverse events is actually 17 reported either to the manufacturer or to the 18 FDA, okay? 19 A. Yes. 20 Q. Assuming that it's only one in 21 ten, and that stays the same pretty much across 22 the board, is it assumed that that's -- say you 23 only have one report of a rash, but you're 24 assuming that there's probably nine other adverse Page 441 1 events related to a rash that are out there that 2 go unreported, does that assumption stay the same 3 across the board or do you ever manipulate that 4 assumption either up or down in relation to any 5 events? 6 A. The only way I can answer that 7 is to say that with a given -- there are lots of 8 factors that would drive up the reporting rate, 9 and I think some of that's been published by the 10 FDA. If indeed you're at one in ten, as your 11 assumption is, and let's say there's an article, 12 now all of a sudden the assumption would be that 13 you're going to increase that rate. But if you 14 have, let's say, a doubling effect of those 15 events from one period to the next, and the 16 denominator stays the same, you're going to 17 generate the report even though in the real world 18 you probably do not have an increased frequency. 19 Q. If a computer generates an 20 increased frequency report, is it automatically, 21 without question, reported to the FDA? 22 A. Yes. 23 Q. Would you agree with me that 24 after Doctor Teicher's article came out and the Page 442 1 media publicity on this case, like the lawsuits, 2 et cetera, that the reporting of adverse -- 3 suicidality related adverse events on Fluoxetine 4 jumped? 5 A. That's a reasonable assumption, 6 but I don't have the data in front of me. 7 Q. But you would agree with me 8 that there was a fairly substantial increase in 9 reports of suicide related events after the media 10 hit? 11 A. I would assume that would be 12 the case. 13 Q. And theoretically, if those are 14 reported in the DEN, the computer should kick out 15 an increased frequency report on the suicidality 16 adverse events, right? 17 A. Yes. 18 Q. Was that automatically sent to 19 the FDA or was there some determination made that 20 it really wasn't an increase in events because it 21 was just a media blitz type of reaction? 22 A. We would not -- regulation -- 23 from what I remember, the regulation doesn't give 24 you that kind of flexibility. Page 443 1 Q. Okay. What did Lilly do as far 2 as reporting to the FDA the response to that 3 increased reporting of suicidality related 4 adverse events after the media hit? 5 A. I can't tell you what the 6 specific action steps were. 7 Q. Was an effort made by Lilly to 8 report all of those media reported suicidal acts 9 or ideations to the FDA for the 1639s? 10 A. As I recall, that's true. I 11 remember a lot of newspaper articles, and I 12 remember it was very difficult for us to 13 determine whether some were new events or whether 14 they were the same reported event that was 15 appearing in, let's say, the Washington Post and 16 another paper and another paper. And so we were 17 sending an awful lot of reports whenever things 18 hit the media without really understanding 19 whether it was a duplicate or not. 20 Q. Was a determination ever made 21 as to whether or not there were numerous 22 duplicate reports sent to the FDA? 23 A. There were times that we were 24 able to ascertain that at some point later in Page 444 1 time. 2 Q. We talked about earlier some 3 percentages of duplicate reports that were 4 deleted from the DEN system? 5 A. Right. 6 Q. And I think you said somewhere 7 between one and five percent? 8 A. No, I don't think I did say 9 that. 10 Q. What did you say? 11 A. I think I said under one 12 percent was my guess. 13 Q. That were deleted because they 14 were found to be duplicate? 15 A. Right. 16 Q. Would that include the reports 17 on the media that may have been double reports? 18 A. It would include anything if it 19 was a known duplication. If it was not known, 20 then it would not be deleted. 21 Q. But as far as your testimony is 22 concerned, while you were in the DEU less than 23 one percent of the reports entered into the DEN 24 were deleted because they were duplicated? Page 445 1 A. That would be my estimate, yes. 2 Q. Any other reasons why DEN 3 reports were deleted? 4 A. If a report was a mistake to 5 begin with, that it was not our product. 6 Q. Okay. It was an adverse event, 7 but it didn't -- 8 A. It might not have been on 9 Prozac or Ceclor or whatever, it might have been 10 on another company's product. After we called 11 the site, we may have got clarification on that. 12 Q. Any other reasons why DEN 13 reports would be deleted? 14 A. That's the only two that would 15 come to mind. 16 Q. What process would someone have 17 to go through to have a report deleted from a 18 DEN? 19 A. They had to file some sort of a 20 request to do that. And we had a specific 21 procedure that was set out to do that, but I 22 don't recall what the elements of that were. 23 Q. Did you have, as the head of 24 DEU, manager of DEU, did you have to approve the Page 446 1 deletion of any given report from the DEN? 2 A. I don't recall that, no. 3 Q. Was there anybody specifically 4 charged with the responsibility of determining 5 whether or not it was appropriate to delete a 6 given report in the DEN? 7 A. There was an output called the 8 deletion report that was provided to individuals 9 after that request had been made. 10 Q. How often would that -- 11 A. So if anyone ever attempted to 12 delete something that was inappropriate, I think 13 you can safely say they would run into serious 14 disciplinary action. But I don't remember that 15 ever occurring. 16 Q. Who would review the deletion 17 reports? 18 A. I don't remember now who was 19 all on that list. 20 Q. Would you review them? 21 A. It seems like I may have seen 22 those, and I remember having some discussion. 23 But again, I can't -- I really couldn't testify 24 to what the specifics were in this process. Page 447 1 Q. Would it be somebody else in 2 the DEU that would review them or somebody 3 outside the DEU? 4 A. I can't recall. 5 Q. Did Doctor Leigh Thompson 6 review them? 7 A. I don't remember that he was, 8 no. 9 Q. How about any of the clinical 10 research physicians, were they charged with that 11 duty? 12 A. Again, I don't remember now the 13 process that we had in place. 14 Q. Okay. I think we got off 15 track, and if I'm wrong, please remind me because 16 I'm starting to get a little tired, but -- 17 A. Can we take a break? 18 MS. ZETTLER: Sure. 19 (A SHORT RECESS WAS TAKEN.) 20 Q. If you could go back to Exhibit 21 1, please. 22 A. Yes. 23 Q. At the bottom it talks about a 24 new work routine being set up to take in calls Page 448 1 related to reports of adverse events regardless 2 of the origin of the adverse events. Do you see 3 that? 4 A. Yes. 5 Q. Was there a period of time when 6 the DEU was processing clinical trial adverse 7 events? 8 A. Not other than serious reports. 9 Q. What do you mean down there 10 when you say regardless of origin? 11 A. I don't know, I'm not sure why 12 I put the statement in at the time, but 13 regardless of where reports came from, their job 14 was to handle those, whether they were mailed in 15 or faxed in, brought in by Pony Express or 16 whatever it was. 17 Q. Okay. 18 (PLAINTIFFS' EXHIBIT NO. 9 WAS 19 MARKED FOR IDENTIFICATION AND 20 RECEIVED IN EVIDENCE.) 21 Q. Have you had a chance to look 22 at the exhibit? 23 A. Uh-huh, yes. 24 Q. Earlier I asked you if you knew Page 449 1 somebody named Claude Bouchy. Do you remember 2 that? 3 A. Yes. 4 Q. Okay. Does this exhibit 5 refresh your recollection as to who Claude Bouchy 6 is? 7 A. No, I still don't know who 8 Claude Bouchy is. 9 Q. Earlier I asked you about a 10 Lilly policy of mapping intentional overdose to 11 overdose and accidental overdose to overdose, et 12 cetera. Do you remember that? 13 A. Uh-huh, yes, I do. 14 Q. Does this refresh your 15 recollection as to that policy? 16 A. Not specifically. I have to 17 say that I can't remember this particular 18 memorandum, and the reason for that might be 19 attributed to the fact that I didn't handle it, 20 that perhaps Doctor Talbott did or one of the 21 other folks did. It doesn't really -- even 22 looking at it here -- I get an awful lot of mail, 23 and what we try to do is to make sure that things 24 get handled and that everyone's not going to be Page 450 1 involved with it, but I don't remember being 2 involved with discussion on this. 3 Q. The third full paragraph of the 4 E-mail says since late '88 or early '89, per 5 Prozac research physician request, and then it 6 goes on to state the various mapping guidelines; 7 correct? 8 A. Right. 9 Q. Intentional overdose maps to 10 overdose, accidental overdose maps to overdose, 11 suicide attempt other than overdose is used for -- 12 maps to suicide attempt, et cetera; correct? 13 A. Right, that's what it states 14 here. 15 Q. Do you have any reason to 16 believe that this isn't true? 17 A. That what Rick Huddleston had 18 reported was wrong? 19 Q. Right. 20 A. No, I have no reason to 21 disbelieve that. 22 Q. Do you have any idea why 23 clinical research physicians for Prozac would 24 have requested that intentional overdose map to Page 451 1 overdose as well as accidental overdoses mapping 2 to overdose as event terms? 3 A. No, I couldn't offhand. Again, 4 I'm not familiar with that issue. 5 (DISCUSSION OFF THE RECORD.) 6 (PLAINTIFFS' EXHIBIT NO. 10 WAS 7 MARKED FOR IDENTIFICATION AND 8 RECEIVED IN EVIDENCE.) 9 Q. We just noted that there's a 10 portion, at least the signature line of the 11 E-mail is missing from the exhibit; correct? 12 A. Right. 13 Q. So we have no way of really 14 telling who sent this E-mail, do we? 15 A. Correct. 16 Q. Regardless, it's an E-mail 17 dated April 18, 1990, and it's to a number of 18 people and you're carbon copied on it; correct? 19 A. Yes. 20 Q. Earlier we talked about the 21 definition of life-threatening, and you said 22 while you recalled something along the lines of 23 some eminent danger, you weren't completely sure 24 of what the definition was? Page 452 1 A. Right. 2 Q. Does this refresh your 3 recollection as to what the definition is? 4 A. Yes. Amazing, it's fairly 5 close to what I said. 6 Q. Can you tell us now, based on 7 this document, what your understanding is of the 8 definition of life-threatening as applied by 9 Lilly was? 10 A. Well, here it states that the 11 term life-threatening means the patient is in 12 immediate risk of dying from the reaction as it 13 occurred. That sounds familiar, from what I can 14 recall, to our internal statement. 15 Q. It also goes on to say that the 16 risk of dying needs to be immediate and not 17 merely potential; correct? 18 A. Right. 19 Q. The determination of whether or 20 not an adverse event is life-threatening, under 21 these guidelines, is made by who at Lilly? 22 A. The research physician. 23 Q. So they would be the ones that 24 would determine whether or not the patient was in Page 453 1 immediate risk of dying from a reaction as it 2 occurred? 3 A. Correct. 4 Q. They would also be the one that 5 would determine that it was an immediate, not 6 just a mere potential risk of dying; correct? 7 A. Right. 8 Q. To your knowledge was that ever -- 9 was that procedure or policy ever changed 10 throughout the time that you were in the DEU? 11 A. I do recall discussions about 12 life-threatening, in fact I remember this 13 particular memorandum. And I think we did go 14 back and revisit just to make sure that everyone 15 had the same understanding of what these terms 16 were. 17 Q. Okay. Was there a difference 18 of opinion or a problem with interpretation that 19 you were addressing with this discussion? 20 A. I don't think there was a 21 problem with interpretation, but I know that 22 there was usually an academic discussion that 23 took place at times to fully understand what the -- 24 to assure that we had a full understanding of the Page 454 1 terms across the division. 2 Q. Was there a discussion related 3 to life-threatening with regards to any specific 4 adverse event, such as, for instance, suicide, 5 suicidality? 6 A. I do not recall that coming up 7 specific to suicidal ideation or anything related 8 to suicide. 9 Q. How about homicidal ideation or 10 intentional injury to others? 11 A. No. 12 (PLAINTIFFS' EXHIBIT NO. 11 WAS 13 MARKED FOR IDENTIFICATION AND 14 RECEIVED IN EVIDENCE.) 15 Q. Have you had a chance to review 16 the exhibit? 17 A. Yes. 18 Q. I'm sure Larry will point this 19 out, but I will be up front from the start that 20 this is a compilation of documents that were 21 pulled from the documents produced as part of 22 your file. 23 A. Okay. 24 Q. There are a number of copies of Page 455 1 this letter in your file, I would say as many as 2 fifteen. The original letter attaching other 3 letters, but only a few copies -- one copy with 4 the attachment of the letters. If you look at 5 the fifth page of the exhibit, it's Pz 962 1757, 6 it looks like somebody forgot to mark out Mister 7 Graedon's name or Graedon's name at the bottom 8 there. 9 A. Uh-huh. 10 Q. Does this refresh your 11 recollection as to who Joe Graedon is? 12 A. I think he was a writer of 13 something, I don't remember now what it was. He 14 was some sort of an author of some journal or 15 something. Yes, I do, I remember getting this, 16 yes. 17 Q. Okay. Do you remember what 18 journal Mister Graedon was associated with? 19 A. No, I don't. 20 Q. Was it an industry journal, 21 medical or psychiatric journal? 22 A. I can't tell you, I just know 23 that he was an author of some publication of 24 sorts because when I got the letter, I do Page 456 1 remember that I had seen his name somewhere 2 before. 3 Q. Do you recall what area of the 4 country he's located in? 5 A. No, I don't. 6 Q. I take it 1639s were filled out 7 for the adverse events that he reported to you? 8 A. Yes. I would probably refer to 9 Doctor Thompson's letter on the back page 10 indicates that response that was made. 11 Q. Okay. The letter dated June 12 19, 1990? 13 A. Right. 14 Q. You said Doctor Tollefson or 15 Doctor Thompson, looks like it's Thompson. 16 A. This is Doctor Thompson. 17 Q. Why was Paul Leber CC'd on that 18 letter, if you know? 19 A. Doctor Leber would be the head 20 of the division at the FDA that has 21 responsibility for these kinds of products, these 22 CNS types of products. 23 Q. Was he carbon copied on all 24 letters written by Lilly personnel in response to Page 457 1 adverse event reports? 2 A. No. Most things that would go 3 down that were, I would say, out of -- that were 4 routine, would go down in 1639s, and would go to 5 a division -- I don't remember, we didn't have 6 any special communication with that, that was 7 just standard operating procedure. This was 8 recognized as a different type of a report that 9 came in, and obviously Doctor Thompson thought it 10 was relevant to make sure that people at the FDA 11 were aware of this going on, and it's part of our 12 practice that we felt that things needed to have 13 additional communication and understanding, and 14 people would take the option to proactively do 15 that. 16 Q. What was different about Mister 17 Graedon's report of these adverse events as 18 opposed to other reports of suicidal ideation or 19 attempts? 20 A. I think you probably have to 21 talk to Doctor Thompson about that. But as I 22 say, I remember that doctor -- or Mister Graedon, 23 whatever he was, was an author, and so it may 24 have been just an attempt to make sure that FDA Page 458 1 people were aware of this information. 2 Q. Okay. On the the fifth page, 3 Pz 962 756, in the right-hand corner there are a 4 bunch of numbers listed? 5 A. Up here, yes. 6 Q. Can you tell me what those 7 numbers represent? 8 A. I don't know for sure. If I 9 had to guess, I would say those are the control 10 numbers for these adverse event reports that came 11 in, one, two three, four, five, six -- there's 12 six of them down there. 13 Q. Manufacturer control number is 14 something that's assigned by Lilly to an adverse 15 event; correct? 16 A. That's correct. 17 Q. And is that also the number in 18 which -- under which the information for that 19 particular patient or event is listed within the 20 DEN? 21 A. Yes, that number there would be 22 a way for us to identify that report. 23 Q. Okay. So when the 1639 is 24 kicked out by the DEN data base, the Page 459 1 manufacturing number that's listed on the 1639 is 2 the same number under which -- that's used in the 3 DEN? 4 A. On what report are you talking 5 about? 6 Q. The 1639. 7 A. Yes, this control number would 8 be on the 1639, it would also be the matching 9 number in DEN. 10 Q. How about clinical trial 11 adverse events, non-serious, were manufacturing 12 control numbers assigned to those adverse events 13 also? 14 A. No, not unless they were put 15 into DEN. 16 Q. Could you track an individual 17 non-serious clinical trial adverse event by the 18 patient investigator project number assigned to 19 that patient? 20 A. In the clinical trial data 21 base, you're talking about? 22 Q. Right. 23 A. I really don't know, I'm not an 24 expert on the clinical trial data base. Page 460 1 Q. Does the FDA have another data 2 base similar to the SRS in which they list 3 clinical trial adverse events? 4 MR. MYERS: Non-serious? 5 MS. ZETTLER: Non-serious. 6 A. Is there a data base in which 7 they list those? 8 Q. Right. 9 A. Not to my knowledge. 10 Q. If you wanted to find out how 11 many non-serious clinical trial adverse events 12 had been reported by Lilly to the FDA to date, 13 how would you go about doing that? 14 A. Well, I suspect I would just 15 write a letter to the division at the FDA, at the 16 division where the product was stored or housed, 17 whatever. 18 Q. Could you call somebody like 19 Mike Dries? 20 A. I don't think so. 21 Q. Is that because he works with 22 spontaneous events? 23 A. Correct. 24 Q. The SRS, to your knowledge, Page 461 1 does that include spontaneous events and serious 2 clinical trial adverse events? 3 A. There would be some, but it 4 would not contain all. 5 Q. All what? 6 A. All serious trial reports. 7 Q. Why not? 8 A. Because that system doesn't go 9 into effect until the product is approved, and 10 the majority of your serious reports that would 11 be going in would have been submitted to the FDA, 12 but not to that system. 13 Q. Are serious clinical trial 14 adverse events, the ones that are reported on the 15 1639s, are they stored separately by Lilly or by 16 the FDA? 17 A. You mail those to the division 18 that has approving responsibility for the drug, 19 of which there are many, so I don't know what 20 their data bases are there. 21 Q. Okay. But the FDA regulation 22 requires that you file a 1639 on the serious 23 clinical trial adverse events? 24 A. No, they require that you Page 462 1 provide a report, they don't specify that it be a 2 1639. 3 Q. But it was Lilly's practice to 4 fill out 1639s on all serious clinical trial 5 adverse events? 6 A. That's correct. 7 Q. And those 1639s -- 8 A. Serious, unexpected, reasonably 9 possibly related trial events. 10 Q. So it had to meet all three of 11 those criteria? 12 A. Right. Otherwise there was not 13 a requirement to provide them. 14 Q. To provide 1639s? 15 A. To provide a report to the IND 16 division unless it met those three criteria, the 17 serious, unexpected -- we're talking about the 18 three and ten-day reports again. 19 Q. Serious, unexpected -- 20 A. Reasonably possibly related. 21 Q. And it was Lilly's policy if an 22 adverse event met this criteria that they would 23 fill out and file with the FDA 1639s in addition 24 to making a three or ten-day report? Page 463 1 A. The ten-day report would be on 2 a 1639. It made it simpler for us to just use 3 one report. The NDA regs required a 1639, the 4 IND required no specific format, and sometimes we 5 crossed-referenced those, we wanted to use the 6 same common reporting format. 7 Q. So theoretically, if you had a 8 death on Fluoxetine, obviously that would be a 9 serious event -- say you had a death on 10 Fluoxetine in a clinical trial, okay, one of the 11 clinical trial participants died of using 12 Fluoxetine. 13 A. Right. 14 Q. That would obviously fall under 15 the serious category; correct? 16 A. Correct. 17 Q. And depending on what was in 18 the package insert, it may or may not be 19 considered expected; correct? 20 A. Correct. 21 Q. Say it was considered 22 unexpected. 23 A. Right. 24 Q. As long as the determination Page 464 1 was made that it was not reasonably -- possibly 2 reasonably connected to the -- related to the use 3 of the drug, then an alert report would not be 4 filed? 5 A. That's correct. If the patient 6 was run over by a car while they were on Prozac, 7 that would be serious, it would be unexpected, 8 but it wouldn't be reasonably possibly related, 9 in most cases. 10 Q. What if a person was run over 11 by a car because they jumped in front of the car? 12 A. If we felt that it was 13 reasonably possibly related to the drug, it would 14 be submitted. And whenever there was a question, 15 the reports went in. 16 Q. So if there was a question 17 whether or not it was reasonably possibly 18 related, you would err on the side of being 19 over-cautious and file the report? 20 A. That's correct. 21 Q. What if somebody at Lilly 22 decided that suicide attempts and suicidal 23 ideation was not related to Fluoxetine but was in 24 fact related to the disease depression? Page 465 1 A. Then it wouldn't be reasonably 2 possibly related. 3 Q. And it wouldn't be reported on 4 a three-day alert report, right? 5 A. It would not be required to be 6 reported, right. Whether it was reported or not, 7 I don't know. 8 Q. Was it Lilly's policy to report 9 all deaths on Fluoxetine or any other Lilly drug 10 regardless of whether or not it was reasonably 11 possibly related? 12 MR. MYERS: When you say report, we're 13 back to the clinical trial. 14 MS. ZETTLER: Right. 15 MR. MYERS: You've met your seriousness 16 criteria, you've met your unexpected. 17 MS. ZETTLER: Right, but you haven't 18 met your reasonably possible related. 19 MR. MYERS: And you want to know if all 20 those went in as a three or ten-day reports? 21 MS. ZETTLER: Right. 22 A. Or anytime? 23 Q. Well, we know that -- I mean 24 any death that's reported spontaneously has to be Page 466 1 reported; correct, in a 1639? 2 A. Any death that's reported. 3 Q. Spontaneous report of death, 4 spontaneous death. 5 MR. MYERS: That's a different 6 question. 7 MS. ZETTLER: He's saying at any time. 8 Q. I'm just -- I'm talking about 9 specifically clinical trial adverse events, okay. 10 A. Right. 11 Q. And we're going through the 12 criteria that you set forth that had to be met 13 for an FDA requirement of a three or ten-day 14 report to be made. 15 A. Okay. 16 Q. To the FDA. 17 A. Right. We're talking about 18 trial reports now, okay. 19 Q. Right, clinical trials, 20 specifically clinical trial reports. 21 A. Okay. 22 Q. So when you are talking about 23 the reports that are entered into the DEN system, 24 you're talking about the reports that meet these Page 467 1 three criteria; correct? 2 A. No, all serious reports -- 3 there's more put in than what comes out in a 4 three and ten-day period. 5 Q. Okay. So all serious, as 6 defined by Lilly, regardless of unexpectedness or 7 reasonably relatedness, all of those that fall 8 under that five criteria or six criteria by the 9 FDA get put into the DEN? 10 MR. MYERS: Clinical trials. 11 MS. ZETTLER: Right. 12 A. Clinical trials. Yes, but the 13 seriousness is not defined by Lilly. You did say 14 by Lilly -- 15 Q. By the FDA. 16 A. -- it's by the FDA. 17 Q. All of those get put in there. 18 A. Right. 19 Q. Regardless of whether or not 20 they're reasonably possibly related or 21 unexpected. 22 A. Right. 23 Q. When we're talking about 24 serious, unexpected and reasonably possibly Page 468 1 related, we're talking specifically now about the 2 three or ten-day alert reports; correct? 3 A. Yes. 4 Q. So you could theoretically have 5 both in the DEN? 6 A. Have both? 7 Q. In other words, all of your 8 three or ten-day alert reports would end up in 9 the DEN, wouldn't they? 10 A. Yes. Three and ten, by the 11 way, are the same thing. In terms of -- all 12 three-day reports do get mailed in in ten days. 13 There is a subset that are -- that you do not 14 have to call in -- anytime something is called in 15 in three days, that's also mailed in in ten days. 16 Q. Okay. But there are some that 17 you do not have to call in, you can mail it in? 18 A. That's correct, right. 19 Q. But when we're talking about 20 serious, unexpected and reasonably possibly 21 related, we're specifically talking about the 22 three or ten-day reporting requirement, right? 23 A. Right. 24 MR. MYERS: Clinical trial? Page 469 1 MS. ZETTLER: Clinical trial. 2 Q. Now is there a similar 3 requirement with regards to spontaneous adverse 4 events that are reported? 5 A. In what way? 6 Q. Like, let's say, you get a 7 report like Doctor Graedon's or Mister Graedon's 8 report of people who committed suicide while 9 using Fluoxetine. 10 A. Right. 11 Q. Do you have a regulation -- is 12 there a regulation at the FDA under which you 13 have to report that adverse event to Lilly within 14 a certain period of time? 15 MR. MYERS: To Lilly? 16 A. To the FDA. We would report 17 these within fifteen days. 18 Q. Okay. Is that a requirement of 19 the FDA? 20 A. As I'm trying to remember, if 21 you do not have death in your package literature, 22 death is an outcome of seriousness, obviously, 23 and if death is not noted, let's say you have a 24 granulosis -- granulocytosis due to death is Page 470 1 reported. If that's in your label, then that 2 would be expected and you would not have to 3 report that in a fifteen-day because it was 4 already known. But if it did not say anything 5 about death, then you would submit it in fifteen 6 days. 7 Q. Okay. So for instance if 8 somebody suffered liver failure as a result 9 ingesting Fluoxetine and died, you would have to 10 submit that in fifteen days if it was not 11 reported in the package insert? 12 MR. MYERS: I object to the form only 13 to the extent your question assumes some 14 causation, and I don't think that's part of the 15 mix that he's testified to. You said Fluoxetine 16 caused the liver failure as opposed to just a 17 happening. 18 MS. ZETTLER: It doesn't matter if it 19 caused it or not. 20 MR. MYERS: Right, that's what I'm 21 saying, and that's why I object to the form. 22 MS. ZETTLER: Obviously if it caused 23 it, it should be reported, shouldn't it? 24 MR. MYERS: If it did, but what I'm Page 471 1 saying is that causation does not affect what 2 he's been talking about in a spontaneous report, 3 that's what he testified to earlier. 4 Q. We're talking about something 5 different, I think, we're talking about a 6 spontaneous report that has to be made within 7 fifteen days of receipt. Is that different from 8 the normal -- is that an across-the-board 9 requirement with regards to adverse events that 10 are reported spontaneously, are you supposed to 11 report them all within fifteen days of receipt? 12 A. No, just those that meet the 13 criteria or a fifteen-day spontaneous, which were 14 serious and unexpected, which you may know that, 15 though. 16 Q. That's what I wanted to 17 clarify. And it doesn't matter whether or not 18 it's caused by the drug; correct? 19 A. That's correct. 20 Q. So in my hypothetical, if you 21 knew that it was caused by the drug, but it 22 wasn't reported in the package literature, it 23 should still be reported as an unexpected event; 24 correct? Page 472 1 A. That's true. And in addition 2 to that, those that are not caused by the drug 3 would also go in in the same time frame. 4 Q. Right, as long as it's serious 5 and unexpected? 6 A. Right. 7 Q. Okay. 8 MR. MYERS: I'm sure glad we cleared 9 that up. 10 Q. Let's go back to the 11 subsyndromal syndrome again. Is this -- this is 12 a Fluoxetine related study; correct? 13 A. Yes. 14 Q. Besides Fluoxetine, are there 15 any other drugs that are being tested, in other 16 words are there comparitor drugs? 17 A. I don't recall if there is, no. 18 Q. Are there other drugs that are 19 being tested? 20 A. I don't recall that there are, 21 no. 22 Q. How about placebos, are 23 placebos being used? 24 A. It seems to me that placebo was Page 473 1 involved with that. I couldn't confirm that a 2 hundred percent, but that's my impression. 3 Q. Was a placebo used in a washout 4 period? 5 A. I don't know. 6 Q. In other words are some people 7 being prescribed Fluoxetine and others being 8 blinded with a placebo control? 9 A. I don't remember that, and I 10 don't know that I even knew that. 11 Q. But you do know that Fluoxetine 12 is being tested in the study? 13 A. It's going to be looked at with 14 subsyndromal syndrome. 15 Q. The study is going to involve 16 patients on Fluoxetine? 17 A. Yes, there would be patients on 18 Fluoxetine. 19 (PLAINTIFFS' EXHIBIT NO. 12 WAS 20 MARKED FOR IDENTIFICATION AND 21 RECEIVED IN EVIDENCE.) 22 Q. Do you recognize this document? 23 A. Not really, no. 24 Q. Have you seen similar Page 474 1 documents? 2 A. Similar documents. 3 Q. In other words listing FDA 4 questions regarding labeling and setting out 5 Lilly's response or proposed response? 6 A. I couldn't honestly answer 7 whether I have seen other ones like that or not. 8 I was involved with the medical editorial 9 services group, as we had talked about before, so 10 there were questions that I had seen regarding 11 labeling, but I don't remember seeing any other 12 one like this. 13 Q. Could you turn to the last page 14 of the exhibit? It says adverse reactions 15 commonly observed, and it starts talking about a 16 consult of a, quote, seratonin syndrome, unquote, 17 characterized by agitation, anxiety, insomnia, 18 tremor, nausea, vomiting and headache. Are you 19 familiar with that? 20 A. No, I'm afraid I'm not. 21 Q. Do you recall adverse event 22 reports of seratonin syndrome being entered into 23 the DEN system? 24 A. No, I can't say that I have. Page 475 1 Q. Are you familiar with the 2 Fluoxetine international gathering -- data 3 gathering project in which Lilly employees went 4 over to Europe and other countries and worked 5 with the affiliates to gather and transfer 6 clinical trial data back to Indianapolis sometime 7 in 1990, late 1990? 8 A. I can remember people gathering 9 information, but I don't know that I could tell 10 you what that was about because I was not one of 11 the participants in that process. 12 Q. Do you recall in late 1990 an 13 influx of European or outside the U.S. related 14 adverse events being reported to the DEU? 15 A. It seems like we did have some 16 increase in that period, yes. 17 Q. What was done by DEU in 18 response to those increases, anything? 19 A. I don't know that there was 20 anything that was done. The drug was marketed in 21 Europe later than it was in the U.S., so one of 22 the factors would have had to have been the fact 23 that the drug was just being given to patients in 24 any appreciable number in that period. Page 476 1 Q. It's your testimony that the 2 first country in which Prozac was marketed was in 3 the United States? 4 A. No, that was not my testimony. 5 As I recall, the large numbers of patients that 6 began to get Prozac, because of most of the 7 countries have a later approval after the U.S., 8 would prompt increased sale of units, and 9 consequently increased numbers of adverse events. 10 Q. The drug was approved for 11 marketing in South Africa before it was approved 12 in the United States, wasn't it? 13 MR. MYERS: You're talking about 14 Europe? 15 MS. ZETTLER: Outside the U.S. 16 A. I don't know what the -- I 17 don't know what the order was, I just know that 18 major countries such as Germany were approved 19 much later, and those countries have a much 20 larger population than South Africa would have. 21 Q. How about any other European 22 countries, are there any European countries where 23 the drug was approved for marketing prior to the 24 United States? Page 477 1 A. It seems like there were, but I 2 don't recall any major European countries that 3 had substantial populations that were approved 4 before the United States. 5 Q. Were you involved in any way in 6 the preparation for the drug advisory committee 7 meeting that was held in September of 1991 on the 8 safety of Fluoxetine? 9 A. I was aware of it, I was not 10 involved with it. 11 Q. How about people within your 12 department, were they involved? 13 A. It seems to me we had a 14 representative from the drug epidemiology unit. 15 Q. Who was that? 16 A. I'm not sure who it was at that 17 time, and the reason I say that is that the 18 responsibilities continued to shift in the drug 19 epidemiology unit, and I'm not sure who the 20 person was that was involved with that. 21 Q. When you say a representative, 22 what do you mean, representative to what? 23 A. A person that would be 24 designated on the part of the drug epidemiology Page 478 1 unit to work with a team of people who were 2 gathering information. 3 (PLAINTIFFS' EXHIBIT NO. 13 WAS 4 MARKED FOR IDENTIFICATION AND 5 RECEIVED IN EVIDENCE.) 6 Q. Have you had a chance to look 7 at Exhibit 13? 8 A. Yes. 9 Q. Again, it appears to be three 10 drafts of the same memorandum; correct? 11 A. No. 12 Q. Okay. 13 A. The third one has either a 14 different alignment or different CCs. I haven't 15 looked down the list of people, but there's -- 16 well, there's thirteen on each, but the order is 17 different and I haven't compared to see if 18 they're all the same thirteen. Some are listed 19 as CC recipients, and the others are major 20 addressees on the last version. 21 Q. Okay. How about the content of 22 the memorandum? 23 A. What about it? 24 Q. It looks essentially the same Page 479 1 as the two drafts, doesn't it? 2 A. At first glance, it appears to 3 be -- no, it's not. 4 Q. In what way is it different? 5 MR. MYERS: I object to the form only 6 to the extent, you know, the three documents 7 speak for themselves, and I don't know that it's 8 fair to make this witness go through the exercise 9 of showing you where they're different. I'm sure 10 they appear to be marked differently, and that's 11 all explanatory on the face of the document. 12 Q. Why is the last one different 13 than the other two? 14 MR. MYERS: He's not a doctor. 15 Q. I'm sorry, I'm elevating him, 16 I'm sorry, although it all depends on your point 17 of view. After the past couple of days, Mister 18 Noone, you may not think that's an elevation. 19 Anyway -- 20 A. On the first document, under 21 three C, you have a note, and under the last 22 document, the note is not there, and there is a 23 D. 24 Q. Okay. Page 480 1 A. And I haven't tried to 2 understand all the differences there. 3 Q. Does this refresh your 4 recollection as to the international data 5 gathering project? 6 A. Not really, other than the fact 7 that I was aware of international data gathering 8 projects. This confirms that there was one with 9 Fluoxetine. By virtue of the fact that I am a 10 CC, probably indicates that I paid probably 11 little attention to this. 12 Q. Okay. Is there a policy at 13 Lilly where people who are listed as CCs are not 14 required to respond to E-mails or memorandums? 15 A. I don't know that there's any 16 definitive procedure that I've seen written out, 17 but typically, if I receive a CC document, I will 18 normally not respond unless there is something 19 that catches my eye that I think needs my 20 specific input. So it would be on exception 21 basis. 22 Q. Okay. If you look at the last 23 page of the exhibit, it talks about collecting 24 information regarding suicidality related events Page 481 1 and bringing it back to the United States or 2 transferring it back to the United States; 3 correct? 4 A. Where are you reading, I'm 5 sorry? 6 Q. With regards to the case report 7 forms, three. 8 A. Okay. 9 Q. Is there any reason, to your 10 knowledge, why this information wouldn't already 11 be contained in the various data bases in 12 Indianapolis? 13 A. I really can't respond, I 14 guess, since I don't really know the background 15 on this project. 16 Q. Well, was it Lilly's policy not 17 to collect and report adverse events occurring on 18 clinical trials outside the United States? 19 A. No, we did collect information 20 on studies as we -- I'll go back and repeat, I 21 guess, what I said before. If it's a serious 22 event, then it was automatically put into DEN. 23 Q. Regardless of where the 24 clinical trial took place? Page 482 1 A. That's correct. 2 Q. And a lot of this information 3 could have been entered into the EARS system that 4 we talked about earlier? 5 A. Could have also been put into 6 EARS, yes. 7 Q. How about non-serious foreign 8 clinical trial adverse events, were those also to 9 be reported to the FDA? 10 A. I don't recall what the 11 reporting obligations are on non-serious. I 12 think we went over that before, I remember that 13 they were put into clinical study reports, but -- 14 Q. Were clinical -- I'm sorry, go 15 ahead. 16 A. But I'm not -- there was no 17 regulatory obligation on those specifically. 18 Q. Were clinical study reports 19 resulting in foreign clinical trials filed into 20 the IND or NDA? 21 MR. MYERS: When you say reports, what 22 do you mean, adverse event reports coming out of 23 those -- 24 MS. ZETTLER: No, trial reports, final Page 483 1 reports. 2 A. Final study reports were 3 provided, yes. 4 Q. On non-U.S. studies? 5 A. Yes. 6 Q. And any adverse events that 7 occurred during those studies would theoretically 8 be reported in those final reports; correct? 9 A. Yes. 10 Q. To your knowledge, was a 11 project such as the Fluoxetine international data 12 gathering project ever conducted on United States 13 clinical trials? 14 A. I don't know. Again, I was not 15 really involved with this project. 16 Q. Was your department asked to 17 provide suicidality or homicidality or violent 18 aggressive behavior related adverse events to 19 anybody at Lilly for analysis in preparation for 20 the advisory committee meeting? 21 A. I don't know what questions 22 were asked in preparation to the FDA advisory 23 committee meeting, although I know there was a 24 tremendous amount of resources that were devoted Page 484 1 to that project, a lot of time and effort on the 2 part of personnel. But I couldn't tell you about 3 what questions were all asked. 4 Q. How about in your department, a 5 lot of time and energy and personnel devoted by 6 your department to the project? 7 A. Yes, I do recall that the DEU 8 was spending time with that project. 9 Q. In what period of time? 10 A. Prior to the FDA advisory 11 meeting. 12 Q. Early 1991? 13 A. When was the advisory meeting? 14 Q. September 1991. 15 A. Certainly in the middle part of 16 the year. I don't know how early it went back. 17 Q. How about in relationship to 18 Doctor Beasley's meta analysis article that was 19 ultimately published in the British Medical 20 Journal? 21 MR. MYERS: The question is did his 22 department do some sort of a similar -- play a 23 similar role? 24 MS. ZETTLER: Right. Page 485 1 A. I don't know, I don't remember 2 seeing that. 3 Q. Would you agree that the drug 4 advisory committee meeting on Fluoxetine, as it 5 related to suicidality and violent aggressive 6 behavior, was important to Eli Lilly? 7 MR. MYERS: Before he answers, let me 8 object to the form, that I think you have 9 misstated and mischaracterized what the subject 10 matter of the meeting was. You've identified a 11 specific subject matter, and I think that is an 12 erroneous assumption. Certainly they took up the 13 question, but I don't believe that that was the 14 subject matter of the meeting specifically. 15 MS. ZETTLER: Okay. 16 MR. MYERS: You can ask Mr. Finz, he 17 can probably tell you, he was there. 18 MS. ZETTLER: You're so proud of 19 yourself. 20 MR. MYERS: But go ahead. 21 Q. Anyway, do you know what the 22 subject matter of the 1991 drug advisory 23 committee meeting on Fluoxetine was, Mister 24 Noone? Page 486 1 MR. MYERS: Same objection, you're 2 making the same assumption. Tell her if you 3 know. 4 A. I'm not sure about all the 5 content of the meeting. I was aware that there 6 was to be discussion concerning Fluoxetine, 7 Prozac and suicidal ideation, but I really was 8 not a participant in that process. 9 Q. Are you aware of any other 10 subjects related to Fluoxetine that were going to 11 be discussed at that meeting? 12 A. No. 13 Q. Was the main focus of the large 14 amounts of time, effort and personnel that you 15 just talked about being devoted to that meeting 16 on suicidality and Fluoxetine? 17 A. I would assume so. 18 MR. MYERS: Off the record. 19 (DISCUSSION OFF THE RECORD.) 20 Q. To your knowledge, has there 21 ever been a causal relationship determination 22 made on Fluoxetine and suicidality at Eli Lilly? 23 A. No. 24 Q. To your knowledge, has there Page 487 1 ever been a causal relationship determination 2 made with regards to Fluoxetine and violent 3 aggressive behavior and homicidal ideation made 4 at Eli Lilly? 5 A. Not to my knowledge. 6 Q. To your knowledge has a causal 7 connection to either one of those, either 8 suicidality or homicidality, ever been dismissed 9 by anyone at Eli Lilly? 10 MR. MYERS: Object to the form and the 11 use of the term dismissed, that's awfully vague. 12 Answer if you can. 13 A. State the question again. 14 Q. Sure. To your knowledge, has 15 anybody at Eli Lilly dismissed a causal 16 relationship between the use of Fluoxetine and 17 either suicidal or homicidal ideation or violent 18 aggressive behavior? 19 A. I don't know, I can't answer 20 that question. 21 Q. Okay. 22 MS. ZETTLER: I'll let the record 23 reflect that I do have at least a couple more 24 hours worth of questions, probably more. It's Page 488 1 our understanding that Mister Noone has personal 2 problems that he needs to deal with, so we're 3 agreeing to stop the deposition at that time, but 4 we will make a motion to bring him back to finish 5 up the deposition. 6 MR. MYERS: I understand your position, 7 and just so our position is clear, this is the 8 fourth day of Mr. Noone's deposition, he's 9 testified probably in excess of twenty hours on 10 these subjects for you and your colleagues, and 11 we're just simply not in a position to 12 voluntarily produce him again, and I think that 13 the suggestion that you make some application for 14 relief would be the appropriate way to handle it 15 as opposed to getting in a big stink and big 16 fight about it. 17 MS. ZETTLER: Well, I don't need to get 18 into a big fight about it either, but I do want 19 to make the record clear that with regards to 20 this case, Fentress versus Shea Communications, 21 Mister Noone has testified for two days and not 22 for four. 23 MR. MYERS: Right, he's been an 24 extremely compliant witness for two days, and Page 489 1 there has been a lot of objections and there's 2 been a lot of ground covered. Regretably, some 3 of it was ground that was covered the last time, 4 but I don't have any control over that so I think 5 we ought to just let some third party look at 6 that and decide what to do. 7 MS. ZETTLER: I'm not saying he wasn't 8 cooperative, Larry, or anything like that. I'm 9 saying he knows a lot about a lot and we need to 10 talk about it. 11 MR. MYERS: No questions. 12 MR. SMITH: No further questions. 13 MR. RUIZ: No questions. 14 (THE WITNESS WAS EXCUSED.) Page 490 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 MICHAEL NOONE 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 25TH DAY OF 19 OCTOBER, 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 491 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, MICHAEL NOONE, THE UNDERSIGNED 9 DEPONENT, HAVE THIS DATE READ THE FOREGOING PAGES 10 OF MY DEPOSITION AND WITH THE CHANGES NOTED 11 BELOW, IF ANY, THESE PAGES CONSTITUTE A TRUE AND 12 ACCURATE TRANSCRIPTION OF MY DEPOSITION GIVEN ON 13 OCTOBER 19TH AND 20TH, 1993 AT THE TIME AND PLACE 14 STATED THEREIN. 15 PAGE NO. LINE NO. CHANGE REASON Page 492 1 2 PAGE NO. LINE NO. CHANGE REASON 3 4 5 6 7 8 9 _____________________________ 10 MICHAEL NOONE 11 SWORN TO AND SUBSCRIBED BEFORE ME THIS 12 _____ DAY OF __________, 1993. 13 _____________________________ NOTARY PUBLIC, STATE OF 14 KENTUCKY AT LARGE Page 493 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Page 494 1 DIRECT EXAMINATIONBY MR. SMITH:....................1 2 CROSS EXAMINATIONBY MS. ZETTLER:.................210 3 COMMONWEALTH.....................................400 4 E R R A T A S H E E T..........................400 5 PLAINTIFFS' EXHIBIT NO. 1........................108 6 PLAINTIFFS' EXHIBIT NO. 2........................236 7 PLAINTIFFS' EXHIBITS 3, 4 AND 5..................267 8 PLAINTIFFS' EXHIBIT NO. 6........................305 9 PLAINTIFFS' EXHIBIT NO. 7........................327 10 PLAINTIFFS' EXHIBIT NO. 8........................338 11 PLAINTIFFS' EXHIBIT NO. 9........................365 12 PLAINTIFFS' EXHIBIT NO. 10.......................367 13 PLAINTIFFS' EXHIBIT NO. 11.......................370 14 PLAINTIFFS' EXHIBIT NO. 12.......................386 15 PLAINTIFFS' EXHIBIT NO. 13.......................390 16 17 18 Page 495 1 DIRECT EXAMINATIONBY MR. SMITH:....................7 2 CROSS EXAMINATIONBY MS. ZETTLER:.................260 3 COMMONWEALTH.....................................491 4 E R R A T A S H E E T..........................492 5 (QUESTIONS CERTIFIED.)............................62 6 (QUESTION CERTIFIED.) ............................67 7 PLAINTIFFS' EXHIBIT NO. 1........................137 8 PLAINTIFFS' EXHIBIT NO. 2........................291 9 PLAINTIFFS' EXHIBITS 3, 4 AND 5..................330 10 PLAINTIFFS' EXHIBIT NO. 6........................375 11 PLAINTIFFS' EXHIBIT NO. 7........................403 12 PLAINTIFFS' EXHIBIT NO. 8........................415 13 PLAINTIFFS' EXHIBIT NO. 9........................449 14 PLAINTIFFS' EXHIBIT NO. 10.......................452 15 PLAINTIFFS' EXHIBIT NO. 11.......................455 16 PLAINTIFFS' EXHIBIT NO. 12.......................474 17 PLAINTIFFS' EXHIBIT NO. 13.......................479 18 Page 496