1585 1 IN THE UNITED STATES DISTRICT COURT 2 FOR THE DISTRICT OF HAWAII 3 4 SUSAN K. FORSYTH, ) Civil No. 95-00185ACK Individually and as ) 5 Personal Representative ) Pages 1,585 - 1,812 of the Estates of June M. ) 6 Forsyth and William D. ) Forsyth, and WILLIAM F. ) 7 FORSYTH, JR., ) ) 8 Plaintiffs, ) ) 9 vs. ) ) 10 ELI LILLY AND COMPANY, ) an Indiana corporation, ) 11 et al., ) ) 12 Defendants. ) __________________________) 13 14 TRANSCRIPT OF PROCEEDINGS 15 The above-entitled matter came on for trial on 16 Thursday, March 18, 1999 at 9:15 a.m. at Honolulu, 17 Hawaii. 18 BEFORE: THE HONORABLE ALAN C. KAY 19 United States District Judge District of Hawaii 20 21 REPORTED BY: TINA M. STUHR, RPR, CSR #360 Notary Public, State of Hawaii 22 PACIFIC REPORTING SERVICES UNLIMITED, INC. 23 733 Bishop Street Suite 2090, Makai Tower 24 Honolulu, Hawaii 96813 (808) 524-PRSU 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1586 1 APPEARANCES: 2 For Plaintiffs: ANDY VICKERY, ESQ. Vickery & Waldner 3 2929 Allen Parkway Suite 2410 4 Houston, Texas 77019 5 KAREN BARTH, ESQ. Baum, Hedlund, Aristei, Guilford 6 & Downey 12100 Wilshire Boulevard 7 Suite 950 Los Angeles, California 90025 8 ROY K.S. CHANG, ESQ. 9 Shim & Chang 333 Queen Street 10 Suite 900 Honolulu, Hawaii 96813 11 For Defendant: ANDREW SEE, ESQ. 12 MICHELLE R. MANGRUM, ESQ. Shook, Hardy & Bacon L.L.P. 13 One Kansas City Place 1200 Main Street 14 Kansas City, Missouri 64105 15 EDMUND BURKE, ESQ. Burke Sakai McPheeters Bordner 16 Iwanaga & Estes 737 Bishop Street 17 Suite 3100 - Mauka Tower Honolulu, Hawaii 96813 18 Also Present: Catherine Itai 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1587 1 I N D E X 2 WITNESS ON BEHALF OF DEFENDANT 3 GARY DENNIS TOLLEFSON, M.D. PAGE 4 Direct Examination by Mr. See 1630 Cross-Examination by Mr. Vickery 1720 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1588 1 (Whereupon, the following proceedings were had 2 in open court out of the presence of the jury.) 3 THE CLERK: Civil No. 95-001858 ACK, Susan K. 4 Forsyth, et al. versus Eli Lilly and Company, et al. 5 MR. VICKERY: Good morning, Your Honor. Andy 6 Vickery and Karen Barth and Roy Chang for the 7 Forsyths. 8 MR. SEE: Good morning, Your Honor. Andy See, 9 Michelle Mangrum, and Ed Burke for Eli Lilly and 10 Company. 11 THE COURT: Good morning. I understand there 12 are more objections. 13 MS. MANGRUM: Your Honor, Mr. Vickery has 14 indicated he intends to read some of his discovery 15 responses, and when we discussed that with the Court 16 at the hearing on March 4th, they were admitted 17 subject to a factual predicate, which would have made 18 them relevant in this case, and our objection to his 19 first set, those he's designated in Plaintiffs' 20 Exhibit 173 is that there is no factual predicate in 21 this case which would make them relevant. 22 THE COURT: 173? 23 MS. MANGRUM: Yes. 24 THE COURT: Which ones are they? 25 MS. MANGRUM: The first one is number nine. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1589 1 THE COURT: How many are there? 2 MS. MANGRUM: In 173 there are nine total. 3 THE COURT: These are only admitted for notice? 4 MS. MANGRUM: Yes, sir. 5 THE COURT: They are only admitted for notice 6 assuming there was a foundation. 7 MS. MANGRUM: Yes, Your Honor. These are all 8 requests that Lilly admits that during certain 9 telephone conferences physicians reported to Lilly 10 certain events their patients had experienced at the 11 same time they were taking Prozac. Number nine, for 12 example, states that a few people have gotten so hyper 13 on the drug that they couldn't even sit still during 14 the day, but there's been no evidence in this case 15 that Mr. Forsyth had that problem, and therefore, 16 Lilly's knowledge of that event is not relevant. 17 THE COURT: Mr. Vickery. 18 MR. VICKERY: Your Honor, all of these matters 19 go to the question of whether or not Mr. Forsyth had 20 akathisia and whether Lilly should have warned about 21 akathisia. As Dr. Healy explained very patiently over 22 a long period of time, this disease or this condition 23 manifests itself in several different ways, and the 24 question is really Lilly's notice that physicians were 25 having patients who experienced these conditions. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1590 1 I'm sorry if I seem a little inarticulate. I 2 had no idea what we were talking about this morning. 3 Ms. Mangrum didn't tell me that she had asked the 4 Court to rule on these or was objecting, so I just 5 learned it when Your Honor walked in. But I -- all of 6 these issues go to restlessness, being hyper, jumping 7 out of their skin, all things that directly relate to 8 akathisia, and so if the question is was Lilly on 9 notice that this drug causes akathisia so as to be 10 under an obligation under Hawaii law to warn about 11 that, these all establish notice. 12 These are conferences in Lilly-sponsored 13 events. These are not random things. It is something 14 that Lilly sponsored in a teleconference, and all of 15 these doctors reported these events. That's why the 16 Court admitted them. 17 I don't recollect, although I will take 18 Ms. Mangrum's word for it, that they were admitted 19 under any kind of condition of predicate at all. 20 THE COURT: Well, you know, as I stated several 21 days ago, it was my understanding that any -- all I 22 was doing was ruling on the other objections, but not 23 on foundation. I mean, for instance, the journal 24 notes of June Forsyth, how could I possibly rule on 25 foundation? I mean, someone would have to establish PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1591 1 that that was her handwriting. There's no way I could 2 have ruled on that. 3 MR. VICKERY: I understand that, and that's not 4 an issue. I mean, we agreed that that was her 5 handwriting. We made no objection. 6 THE COURT: I'm just using that as an example 7 of how could I be ruling on the foundation. On the 8 other hand, as far as, if you had an FDA paper that 9 had been certified by the FDA, then that would come 10 in, but anyway, let's go to the next one. Number 11; 11 is that right? 12 MS. MANGRUM: Yes, Your Honor. 13 THE COURT: This one is the attention span? 14 MS. MANGRUM: Attention span, yes, they 15 couldn't work and could not carry on conversations. 16 THE COURT: Okay. Next one, No. 12. 17 MS. MANGRUM: Three people out of fifty that 18 complained of feeling quite hyper and nervous. 19 THE COURT: Next. Thirteen. 20 MS. MANGRUM: Excuse me, yes, Your Honor, 13. 21 A physician reported that he suspected that Prozac had 22 an amphetamine-like action. 23 THE COURT: What's the relevance of that, 24 Mr. Vickery? 25 MR. VICKERY: I expect that their own witnesses PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1592 1 would readily admit that someone that has an 2 amphetamine-like action is the very kind of 3 nervousness, agitation, akathisia -- I mean, there's 4 so many different terms that are used to describe 5 these phenomena, both lay terms like wired, jumping 6 out of our skin, and more technical terms. Depending 7 on who you're talking to, they might use different 8 verbiage, but we're talking about the same phenomenon. 9 THE COURT: Fourteen is jump out of skin, 10 right? 11 MS. MANGRUM: Yes, Your Honor. 12 THE COURT: Seventeen is the next one? 13 MS. MANGRUM: I believe it's 18, Your Honor. 14 MR. VICKERY: Seventeen. No, I was holding on 15 17, Your Honor. She's right. Seventeen not at this 16 time. 17 THE COURT: Eighteen, restless. Is this a new 18 way of spelling akathisia? 19 MR. VICKERY: (Counsel nods head.) 20 THE COURT: A-C-H-I-S-E-S-I-C. 21 MR. VICKERY: That's right. That's why it says 22 sic after it. It's obviously a misspelling. 23 THE COURT: Nineteen, agitation. 24 MS. MANGRUM: Yes, Your Honor. 25 THE COURT: Twenty-one, bopping other people in PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1593 1 the unit. What about that, Mr. Vickery? 2 MR. VICKERY: It's violence towards other 3 people. 4 THE COURT: Pardon me? 5 MR. VICKERY: It's violence towards other 6 people. Lilly is on notice that people on Prozac were 7 bopping other people. 8 THE COURT: Twenty-two is -- 9 MS. MANGRUM: That one Mr. Vickery has skipped 10 and said the next one is 24 that he intends to read. 11 THE COURT: Twenty-four, wired. 12 MS. MANGRUM: Yes, Your Honor. 13 THE COURT: I think that was the word Dr. Healy 14 used, wasn't it? 15 MS. MANGRUM: It may have been, Your Honor. 16 Plaintiffs only -- Mr. Vickery's argument has been 17 this is relevant to Lilly's notice because plaintiffs 18 claim Lilly should have warned about akathisia and 19 these type of events. Their only expert testimony on 20 the issue of failure to warn was that of Dr. Shlensky, 21 and his only criticism was that the warning should 22 have contained information regarding suicide and 23 violence. Nothing about any of these events. 24 THE COURT: Well, I'm going to allow these, 25 again strictly for notice for that limited purpose, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1594 1 otherwise I find that they are relevant. 2 Does that cover all of them? 3 MS. MANGRUM: Just a moment, Your Honor. The 4 next one they have designated is Exhibit 174. That's 5 only Request No. 3, which asks that Lilly admit that 6 Fluoxetine is an activating drug, and our objection to 7 that would be the same, lack of factual predicate 8 because there's no evidence in this case that it had 9 that effect on Mr. Forsyth. 10 THE COURT: This portion Lilly admits that 11 technology has not advanced to the point, is that what 12 you're objecting to? 13 MR. VICKERY: I believe that Ms. Mangrum 14 misspoke, Your Honor. No. 3 on 174 is exactly what 15 you're looking at. It has nothing to do with 16 activation. It has to do with the extent of Lilly's 17 understanding and knowledge about what this drug 18 really does to people. 19 The request was that Lilly cannot explain how 20 Prozac works either for treatment of depression or for 21 other behavioral disorders, and I'm certainly willing 22 to leave off that other phrase. 23 THE COURT: What other phrase? 24 MR. VICKERY: The last phrase "or for other 25 behavioral disorders." PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1595 1 MR. SEE: That's fine. Why don't you do that? 2 MR. VICKERY: Okay. I will do that. 3 THE COURT: I'm not sure I see exactly where 4 you're referring to. 5 MR. VICKERY: In the request itself, Your 6 Honor, Request No. 3. 7 THE COURT: Oh, I see. 8 MR. VICKERY: You see the last phrase? 9 THE COURT: Yes. 10 MR. VICKERY: I'm just going to leave that off 11 when I read it. 12 THE COURT: All right. And with that, there's 13 no objection? 14 MS. MANGRUM: That's right, Your Honor. 15 THE COURT: Have we covered everything? 16 MS. MANGRUM: There's three left in 17 Exhibit 178, and that would be request for admissions 18 No. 16 and No. 20, and then Interrogatory No. 17. 19 THE COURT: 178, 16? 20 MS. MANGRUM: Yes, Your Honor. 21 THE COURT: What is the gross revenue? 22 MS. MANGRUM: No, it's request for admission 23 16. It is -- 24 THE COURT: Are we in 178? 25 MS. MANGRUM: Yes, Your Honor. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1596 1 MR. VICKERY: 178 contains both request for 2 admissions and interrogatories, Judge. She's talking 3 about the request for admission No. 16 that Prozac has 4 an activating effect in some people. 5 THE COURT: What's the objection to that? 6 MS. MANGRUM: Again, that there's no evidence 7 that this drug had an activating effect in 8 Mr. Forsyth, so Lilly's knowledge of that or its 9 statement regarding activation is not relevant. 10 THE COURT: What's the Prozac miracle? 11 MS. MANGRUM: A relief of depression. 12 THE COURT: Is that activating or what? 13 MS. MANGRUM: I believe it's relief of the 14 depressive symptoms and a return to normal. That was 15 Dr. Riggs Roberts' phrase. It's not a phrase used by 16 Lilly or coined by Lilly. 17 THE COURT: Yeah, but you say that there was no 18 evidence as to Mr. Forsyth. 19 MS. MANGRUM: Exactly. I mean, no evidence 20 that he was excessively active or pacing, wringing his 21 hands, doing anything other than returning to his 22 normal state by the observations of physicians and 23 family members. 24 THE COURT: Mr. Vickery. 25 MR. VICKERY: Well, I think the Prozac miracle PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1597 1 is exactly activation as is his anxiousness on the 2 following day, the 24th, to get into the hospital. 3 It's again -- the problem that we have and the Van 4 Putten article, if you want to read it, would help is 5 that the terminology has been so loosey goosey with 6 respect to this phenomenon akathisia. They use 7 agitation, activation, nervousness, restlessness, 8 akathisia, jump out of my skin, feeling wired. I 9 could go on and on. 10 THE COURT: Well, I'm going to allow it. I 11 find it relevant. 12 MS. MANGRUM: The last two, Your Honor, are 13 Interrogatory No. 17 -- 14 THE COURT: Is this in 178? 15 MS. MANGRUM: Yes, Your Honor. 16 THE COURT: Interrogatory number what? 17 MS. MANGRUM: One -- or excuse me, 17. Our 18 objection to that is that the number of times the 19 label has been changed is absolutely irrelevant. 20 Several of the changes referenced in there occurred 21 after Mr. Forsyth's ingestion of Prozac, which would 22 make them subsequent remedial measures. And just the 23 number of times that the label has changed has nothing 24 to do with this case. 25 THE COURT: I think someone has already PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1598 1 testified to this anyway, haven't they? 2 MR. VICKERY: No, sir. There has been no 3 testimony on this. 4 THE COURT: I think one of your experts got 5 that in. 6 MR. VICKERY: I believe he said it could be 7 changed, but I don't think anybody has talked about 8 the number of times that it's been changed. My 9 concern, Judge, is that Lilly is going to try to paint 10 this picture that, oh, boy, our warnings are approved 11 by the FDA and they're just cast in stone. They're 12 just cast in stone. So the fact that Lilly changed 13 the label 28 different times over a ten-year period 14 indicates they're not cast in stone at all. 15 Certainly, none of these get into the subject 16 of subsequent remedial measures because there's no 17 question about the substance of any of these changes, 18 but it -- I mean, it clearly indicates that Lilly can 19 and has changed the label for Prozac -- 20 THE COURT: Wouldn't this be more proper for 21 rebuttal then? 22 MR. VICKERY: Well, I don't think so, Your 23 Honor. We're going to have this morning, you know, 24 Lilly's vice president, Dr. Tollefson, who is, you 25 know, is their guy they're bringing and before he PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1599 1 testifies in my case in chief, I want the jury to 2 understand that they can and have changed this label 3 very frequently. Nearly three times a year. 4 THE COURT: Well, you can bring that on 5 cross-examination, can't you? 6 MR. VICKERY: Okay. I'll do that. 7 THE COURT: All right. Next. 8 MS. MANGRUM: That's the last one, except for 9 17 also asks how much it cost to modify the insert, 10 and our objection would be the same, that that also is 11 not relevant at this time. 12 THE COURT: That does not seem relevant for 13 this purpose. 14 MR. VICKERY: Your Honor, they have said time 15 and again with witnesses, isn't there a risk benefit 16 analysis that you have to do in prescribing a 17 medication, and so -- 18 THE COURT: That's to the treating physician. 19 MR. VICKERY: I understand. But they're the 20 ones that have interjected the notion that we balance 21 benefits and risk, and I think the fact that this can 22 be done with no cost, that it's done frequently 23 without any regulatory problems and without 24 significant cost -- 25 THE COURT: Well, what's a significant cost? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1600 1 MR. VICKERY: I don't know. They won't tell 2 me. 3 THE COURT: You're not going to tell me there's 4 no cost involved. There's some cost. 5 MR. VICKERY: Of course there's some cost. 6 THE COURT: Okay. I rule that irrelevant at 7 this time under 403. It's highly prejudicial and does 8 not have any significant probative value and it would 9 be a waste of time and confusing to the jury. That 10 may become pertinent during the punitive damages 11 phase, if we get to that, though. Have we covered 12 everything? 13 MR. SEE: We have covered all of those, Your 14 Honor. The only other thing we have is really a 15 scheduling matter. I've discussed this with 16 Mr. Vickery. He informs me that other than reading 17 these interrogatory responses and so on that we've 18 just talked about, thereafter, the plaintiffs will 19 rest their case. 20 We do have a motion for directed verdict and 21 would make it, and just -- we kind of would ask the 22 Court's pleasure, if the Court would like to hear it 23 now before the jury comes back, we could certainly do 24 that subject to Mr. Vickery reading -- only reading 25 the interrogatory responses that we've just discussed. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1601 1 If that would be convenient for the Court's schedule, 2 we would offer to do that at this point. 3 THE COURT: That sounds reasonable. Are you in 4 agreement with that, Mr. Vickery? 5 MR. VICKERY: Sure. I think you can take it up 6 whenever you like. 7 THE COURT: All right. 8 MR. SEE: Your Honor, I'll hand up two copies 9 of the pleading. 10 THE COURT: Is that a little epistle here? 11 MR. SEE: It is, Your Honor. 12 THE COURT: This is where Ms. Mangrum was 13 yesterday? 14 MR. SEE: Honestly, I can't testify to that, 15 sir. But I believe I can bottom line what it says in 16 not too long. And they're really -- 17 THE COURT: Well, I can't read much of that, 18 so -- 19 MR. SEE: All right. 20 THE COURT: I've seen it before. 21 MS. MANGRUM: It's 1041 in the book. 22 MR. SEE: It's Exhibit 1041 in our book. It is 23 a blowup of part of the insert. 24 THE COURT: I'm familiar with it anyway. 25 MR. SEE: All right. Your Honor, there are a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1602 1 few grounds for the directed verdict. The first one 2 is this: Plaintiffs have two experts, Dr. Healy and 3 Dr. Shlensky. They both have testified that Prozac 4 caused akathisia in Mr. Forsyth and that from that, 5 Mr. Forsyth proceeded to these other events, that he 6 became suicidal and he became homicidal. 7 There's no evidence in the case from any of the 8 fact witnesses that Mr. Forsyth, in fact, had 9 akathisia. The Ninth Circuit case, which is U.S. 10 versus Various Slot Machines, which we have in the 11 brief, is very clear. The expert opinion has to be 12 based upon facts. There has to be a fact underlying 13 that opinion. And both the plaintiffs' experts, to 14 get to causation, go through akathisia. 15 And the evidence that we have is very 16 straightforward. There is no evidence from any fact 17 witness, either the hospital records, Dr. Roberts' 18 records, Dr. Neal's testimony, Dr. Roberts' testimony, 19 Bill Forsyth's testimony, Susan Forsyth's testimony, 20 Kim Forsyth's testimony, anyone that observed 21 Mr. Forsyth during anytime he was taking Prozac that 22 he had any sign or symptom of akathisia. 23 THE COURT: Well, it seems to me that Dr. Healy 24 did testify that in reading the record, reading the 25 depositions and the reports that from the facts he saw PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1603 1 in those, that he determined in his opinion, which 2 your experts disagree with, but in his opinion that 3 there was akathisia. 4 MR. SEE: I understand that. 5 THE COURT: And there were symptoms of 6 akathisia. 7 MR. SEE: I understand that. He gave that 8 opinion. 9 THE COURT: Based on the facts he saw from the 10 record. 11 MR. SEE: But let's look at what those facts 12 are and how Dr. Healy gets to his opinion. He put in 13 front of the jury five case reports. He said those 14 case reports show that Prozac causes akathisia. 15 That's the Rothschild, Healy, Wirshing, King and so 16 on. 17 THE WITNESS: Controlled clinical studies. 18 MR. SEE: Some would say. Although 19 Dr. Shlensky would not agree with that nor would 20 anyone else in the medical world, but Dr. Healy does. 21 You look at those five case reports, and what 22 do you see, pacing, hand-wringing, inability to sit 23 down, inability to remain still, the very -- what 24 Dr. Healy claims is the very scientific data upon 25 which his opinion rests, and that's it. Those case PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1604 1 reports. Every one of those people had visible, 2 observable signs of psychomotor movement. Every one. 3 So that's what his opinion is based upon. 4 Now, I know he says, well, I've reviewed the 5 record and I've determined that Mr. Forsyth had 6 akathisia, but that opinion has to be based upon fact, 7 and all of the scientific data that Dr. Healy puts 8 forward, every -- there may be one, every one of those 9 people had active movement. Every one. 10 So Dr. Healy's opinion resting upon that data 11 can't support an opinion that Mr. Forsyth had 12 akathisia. It simply can't do it. Because he says 13 the data is here and it says one thing, but I read the 14 factual record and now I'm ignoring my data, and 15 saying this guy had akathisia when Mr. Forsyth had no 16 symptom that is anywhere close to what was in those 17 five case reports. That's my first ground. 18 My second ground is a proximate cause ground, 19 the Wolf versus Lilly, the Oklahoma case. We heard 20 testimony from the only two prescribers, and their 21 testimony was they did not rely upon what the drug 22 company gave them. They made independent decisions. 23 They did their own research. They looked for the 24 articles themselves and did not rely upon what the 25 drug company told them. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1605 1 THE COURT: But I think that Mr. Vickery did -- 2 you know, I acknowledge he made a strong point there, 3 but on the other hand, I think Mr. Vickery did get 4 them to say that if there was a warning that Prozac 5 caused akathisia or Prozac caused death, then they 6 would have considered the warning. 7 MR. SEE: Well, Dr. Roberts -- 8 THE COURT: I will withdraw the latter. 9 MR. SEE: Dr. Roberts gave no testimony about 10 that. Mr. Vickery didn't ask about that. He asked 11 Dr. Neal, and Dr. Neal said Mr. Vickery sent me all 12 this stuff that's been in this trial, it wouldn't have 13 changed my view at all. 14 THE COURT: I don't know what he sent him. 15 MR. SEE: Well, his testimony was he sent him 16 the exhibits from the trial. 17 The other aspect of the proximate cause 18 argument is that both of these doctors testified that 19 they already knew that there was a possibility of 20 suicide in a patient taking an antidepressant drug 21 including Prozac. Already knew it through their own 22 independent knowledge. That's my second ground for 23 proximate cause. 24 My third ground has to do with the adequacy of 25 the warning, and I think I tried to listen very PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1606 1 carefully to what Dr. Shlensky said about his 2 criticism of Lilly's warning. Dr. Healy, of course, 3 gave no opinion, so the only critique we have is what 4 Dr. Shlensky said, and my notes reflect that what 5 Dr. Shlensky said was Lilly did not warn of the 6 possibility of suicide or violent behavior, and that's 7 my criticism. And my recollection is, and I hope the 8 Court's is too, that that's about all he is said. It 9 was pretty short. 10 The Prozac package insert at the time says, 11 with respect to suicide, "the possibility of a suicide 12 attempt is inherent in depression and may persist 13 until significant remission occurs." The second place 14 is under post-introduction reports. It tells the 15 doctor that "Reports of adverse events temporally 16 associated with Prozac include suicidal ideation." It 17 also says in that section that "Voluntary reports of 18 adverse events temporally associated with Prozac 19 include violent behaviors." 20 And although Dr. Shlensky did not make it part 21 of his criticism, the insert also says, "events 22 observed during premarketing evaluation, akathisia is 23 warned against." 24 Now, I just note that for the Court's own 25 information. Dr. Shlensky did not criticize the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1607 1 insert about akathisia. He criticized it about 2 suicide, which is here in two places, and he 3 criticized it about violent behavior, which is clearly 4 specified. 5 THE COURT: But his -- wasn't his concern that 6 it didn't warn that, number one, I guess that's a 7 precaution rather than a warning; is that right? 8 MR. SEE: The first suicide warning is in the 9 precaution section. 10 THE COURT: Right. 11 MR. SEE: That's correct. 12 THE COURT: Not the -- there's a warning 13 section, too, isn't there? 14 MR. SEE: There is a warning section. 15 THE COURT: Right. The precaution section is 16 sort of lower case compared to the warning section. 17 MR. SEE: It follows it, but it's not in a 18 lower case. 19 THE COURT: Yeah, but you know what I mean. It 20 doesn't carry the same emphasis as the warning 21 section. 22 MR. SEE: With respect, Your Honor -- 23 THE COURT: I think one of the experts or two 24 of them -- 25 MR. SEE: It's in two different sections. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1608 1 There's no question about that, but with respect, Your 2 Honor, as I wrote down what Dr. Shlensky said, he 3 said, Lilly's warning did not warn about suicide or 4 about violent behavior. Full stop. 5 THE COURT: And did he say with respect to 6 Prozac or with respect to depression? 7 MR. SEE: He said with respect to Prozac, but 8 I'm saying, if you come down to the post-introduction 9 reports section, it says, "Reports of adverse events 10 temporally associated with Prozac, suicidal ideation 11 and violent behaviors." 12 The warning is that those things had been 13 reported in temporal associations with Prozac. So 14 that section of the insert is not a warning about 15 suicide coming along with depression. 16 THE COURT: It's a precaution that what? 17 MR. SEE: It reads, "Voluntary reports of 18 adverse events temporally associated with Prozac that 19 have been received since market introduction and which 20 may have no causal relationship with the drug, include 21 the following: Suicidal ideations and violent 22 behavior." 23 THE COURT: May have no causal relationship? 24 MR. SEE: That's what it says. Dr. Shlensky 25 did not testify that his criticism was that the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1609 1 warning should say Prozac causes suicide. That was 2 not the tenor of his criticism. It was that the 3 insert did not warn of the risk or possibility of 4 suicide or violent behavior and the fact is, it 5 clearly does. And he really went into no more detail. 6 His warning opinion was very short. So I would submit 7 that the insert, in fact, does warn about exactly what 8 Dr. Shlensky criticized and that's the only opinion in 9 the case about warning. Those are my three grounds. 10 THE COURT: Oh, I thought you said you had 11 more. 12 MR. SEE: I had those three; the causation 13 through akathisia, the proximate cause, both that they 14 already knew about the possibility of suicide and that 15 they may occur in associated events, that's the second 16 one, and the third one is the warning as criticized by 17 Dr. Shlensky is, in fact, adequate. It says exactly 18 what he criticized. 19 THE COURT: Thank you. Mr. Vickery. 20 MR. VICKERY: Your Honor, I, of course, have 21 not had time to read the 13-page brief that 22 accompanies the written motion nor has the Court. I 23 just got it the same time the Court did. 24 THE COURT: Well, do you want to argue this 25 sometime later? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1610 1 MR. VICKERY: I don't think so. He didn't 2 really rely on the law there anyway, but of the 3 evidence and I'm prepared to address the evidence. 4 I think the Court has in the comments to 5 Mr. See hit the nail on the head with respect to all 6 three. With respect to the first ground, no evidence 7 of akathisia, the problem, of course, is as Dr. Healy 8 explained at some length, the difficulty in discerning 9 this condition if one is not looking for it. 10 If you're not forwarned to look for it, either 11 doctor or patient, it's more difficult to find, but we 12 have the testimony of Dr. Neal that he had a 13 constricted effect. We had the testimony of Kim 14 Forsyth that his hands, indeed, were fidgeting when he 15 was on his way to the hospital and we have the 16 testimony -- 17 THE COURT: His knees? 18 MR. VICKERY: Sir? 19 THE COURT: His knees? 20 MR. VICKERY: No, his hands. 21 THE COURT: I thought you said his hands and 22 knees. 23 MR. VICKERY: No, sir, I said his hands were 24 fidgeting as he was on his way to the hospital. We 25 have the testimony of Dr. Healy -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1611 1 THE COURT: Is this something that she did not 2 say in her deposition? 3 MR. VICKERY: That's exactly right. She didn't 4 remember it in her deposition, but the evidence is in 5 the record. I mean, the fact -- 6 THE COURT: I understand. 7 MR. VICKERY: Okay. And then, of course, the 8 testimony of Dr. Healy in looking at the facts, his 9 testimony is based on the facts, on the records, and 10 his opinion can't be ignored, certainly not in the 11 context of a motion for a directed verdict because 12 Mr. See doesn't like the facts he looked at or 13 quibbles with the methodology in which he looked at 14 them. He looked at the records and said based on 15 those records, I believe this man had akathisia. 16 THE COURT: His opinion is based also on the 17 fact that he thought he had mild depression. 18 MR. VICKERY: Exactly. 19 THE COURT: His whole opinion is based on that; 20 whereas, the treating physicians and others thought -- 21 have all opined that it was severe depression. 22 MR. VICKERY: I understand that, and there's a 23 conflict the jury has to resolve based on the 24 credibility that they assess to the various 25 physicians, but that's a traditional jury question. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1612 1 And with that evidence in the record, we're not in a 2 directed verdict context. 3 The second ground -- 4 THE COURT: I just note that the two treating 5 physicians found contrary to Dr. Healy who wasn't even 6 around. 7 MR. VICKERY: You're absolutely right, Your 8 Honor, and for that reason, the jury may choose to 9 give their testimony more credence. I think there are 10 other reasons in which they would tend to discount the 11 testimony of those gentlemen and favor the testimony 12 of Dr. Healy, but my point is quite simply -- 13 THE COURT: And on top of that, as far as the 14 draft warning, which you brought out, in fact, he was 15 being given a sedative along with the Prozac. In 16 other words, there was full compliance. 17 MR. VICKERY: There wasn't full compliance. He 18 discontinued the Xanax. He discontinued the very 19 benzodiazepine. He discontinued that. 20 THE COURT: But he gave him Inderal. 21 MR. VICKERY: He did give him Inderal. 22 THE COURT: And that was to relieve anxiety and 23 he also said that it would relieve any akathisia. 24 MR. VICKERY: I think he said that Inderal 25 would help him sleep. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1613 1 THE COURT: No, he gave him something else for 2 sleep. 3 MR. VICKERY: Okay. I understand the arguments 4 you're making, Your Honor. 5 THE COURT: I'm not making arguments. 6 MR. VICKERY: Or the points. 7 THE COURT: A lot of this doesn't rise to the 8 level of a directed verdict, so go ahead. 9 MR. VICKERY: That's my whole point. I 10 understand the conflicts in the testimony that the 11 Court's pointing out or the conflicts in the evidence 12 from which the jury can go either way on it. My only 13 point is that it's for them to weigh that evidence and 14 decide which way to go. 15 THE COURT: What I have said so far, I think, 16 really undermines the plaintiffs' case, but I'm not 17 sure that it rises to the level of a directed verdict. 18 MR. VICKERY: I agree with you entirely. It's 19 evidence that they brought out that cuts against us, 20 but it's for the jury to decide. 21 The second ground on the Wolf case. As I told 22 the Court before, I was the attorney of record in 23 Wolf. I represented the Wolf children. I understand 24 exactly what happened in that case. 25 THE COURT: You lost on a summary judgment PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1614 1 there? 2 MR. VICKERY: Yes, we did and unfortunately, my 3 clients instructed me to settle the case on appeal, so 4 the Tenth Circuit never got to speak to it. I think 5 the judge was wrong on that case because of the 6 comment Jay presumption, which we've briefed for the 7 Court. I don't think that under Hawaii law that that 8 same result would obtain. I clearly do not, but 9 that's an issue we need not cross at this juncture 10 because Dr. Neal did testify that he would have heeded 11 an appropriate warning from Eli Lilly, so -- 12 THE COURT: Whatever that might be. 13 MR. VICKERY: Whatever that might be. You 14 know, we obviously get into my work product as to how 15 I would argue what that ought to be based on the 16 totality of the evidence, but again, it gets us over 17 the hurdle. 18 THE COURT: I think he did testify he would 19 have acted differently perhaps if the warning had been 20 that Prozac might cause akathisia. 21 MR. VICKERY: Right. 22 THE COURT: And maybe that's in there according 23 to what Mr. See was just saying. 24 MR. VICKERY: Well, I find Mr. See's statements 25 just now to be somewhat extraordinary. I think that PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1615 1 the world community would be shocked to know that Eli 2 Lilly's lawyer just said in open court that they have 3 warned about suicide and akathisia, because as the 4 Court pointed out, these are not in the warning 5 section. They're in the precaution section. The 6 federal regulations, which are in evidence, both 7 parties have asked the Court to take judicial notice 8 of them, make clear distinctions between warnings and 9 precautions, and the section on temporally associated, 10 they specifically say not caused. 11 It's not even a precaution, Judge. It's 12 merely, oh, yeah, by the way, some people who have 13 taken this pill have reported that, you know, 14 subsequent to taking it, they've had these reactions, 15 but don't worry about it. It doesn't cause -- our 16 pill isn't causing this. 17 Of course, separate and apart from that, 18 there's the interrogatory that we just read that shows 19 that this is not the only way that Lilly informs 20 physicians about problems with the drug. So it -- 21 this isn't even -- 22 THE COURT: What's the significance of that? 23 MR. VICKERY: The significance of that is that 24 Lilly had lots of -- under Hawaii law the warning must 25 be adequate to apprise the prescribing physician of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1616 1 the dangers, to bring it to his attention, okay? And 2 so something tucked away in the small print of a 3 section that's not even the warning section of the 4 label is not the only way that Lilly has to comply 5 with the common law of Hawaii in giving an effective 6 warning. They use other means. They use dear-doctor 7 letters. They use detail people. It's just 8 abundantly clear that they have not warned about a 9 risk that this drug causes suicide. 10 They've said it's temporally associated with 11 it, but it doesn't cause it. I mean, they've gone 12 beyond not warning to say it doesn't cause it. 13 THE COURT: But on the other hand, you may have 14 that same -- the bottom line is you may have that 15 result, whether it causes it or not. 16 MR. VICKERY: Sure. You may have that result, 17 but it's common sense that if you're getting 18 information from the manufacturer and it is 19 established, as the Court's already noted, in a 20 hierarchical fashion, they're warnings, then they're 21 precautions, and then they're temporally associated 22 events, and where one puts the words in the label is 23 something that is extremely important. 24 THE COURT: That's Exhibit 114; is that right? 25 MR. VICKERY: I haven't looked at it, Judge. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1617 1 MR. SEE: 1041, Your Honor. 2 THE COURT: 1041? 3 MR. SEE: 1041. 4 MR. VICKERY: So for all of these reasons, Your 5 Honor, I think that there is sufficient evidence for 6 the jury to conclude that Mr. Forsyth had akathisia; 7 that the failure to warn and that this drug were 8 indeed a proximate cause of the deaths of June and 9 Bill Forsyth; and that the warning -- I wouldn't even 10 call it a warning. I would say that there's no 11 warning about this issue, but certainly the 12 information in the package insert was not sufficient 13 under Hawaii law. 14 THE COURT: Well, what is your answer to 15 Mr. See's statement that Dr. Shlensky gave a very 16 limited opinion as to the warning, the inadequacy of 17 the warning? 18 MR. VICKERY: My answer to that, Your Honor, is 19 really twofold. Number one is that Dr. Shlensky -- 20 Dr. Shlensky's testimony gets us to the jury. 21 THE COURT: Pardon me? 22 MR. VICKERY: Dr. Shlensky's testimony 23 certainly gets us to the jury, assuming for a moment, 24 that one has to have expert testimony on the issue of 25 inadequacy of warnings. The Court has not addressed PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1618 1 that, but assuming that that's necessary, his 2 testimony would get us to the jury on that. I don't 3 think that's necessary. I've seen no law that says 4 you have to have expert testimony on what a warning 5 should look like to get to the jury. That the jury 6 can determine that themselves from the totality of the 7 evidence. 8 And that's the second point I have. That 9 when -- if you didn't even have Dr. Shlensky's 10 testimony, if you had Dr. Healy's testimony on the 11 causation, and if you have the other documentary 12 evidence that establish that Lilly was aware of this 13 risk and you have the package insert itself which 14 doesn't warn of this risk, if that was all we had, and 15 it's not, but if that was all we had, I still think 16 that takes the case to the jury on an inadequate 17 warning case under Hawaii law. 18 THE COURT: Well, what's your position as to 19 what the opinion was that was rendered by Dr. Shlensky 20 on inadequacy of warning? 21 MR. VICKERY: My opinion is I honestly would 22 like to read that section of the transcript, Your 23 Honor. I think what he said was that there was no 24 warning about -- 25 THE COURT: Mr. See has it for you there. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1619 1 MR. SEE: I have my notes, which are not the 2 record, but I have my notes. 3 MR. VICKERY: I prefer the court reporter's 4 transcript to Mr. See's notes, Your Honor. I can't 5 read his handwriting. I think that -- I don't 6 recollect exactly what he said. I just feel quite 7 comfortable that the evidence is sufficient to take 8 this case to the jury. 9 THE COURT: Thank you. 10 MR. SEE: Could I have 30 seconds, Your Honor? 11 THE COURT: Very well. 12 MR. SEE: I don't know if it's possible for the 13 court reporter to look at this, but Dr. Shlensky 14 testified to this opinion after the 2:15 break. It 15 was the first thing he testified about. And here's 16 what my notes say. He was asked, do you have an 17 opinion whether Lilly gave a fair and appropriate 18 warning about violence or suicide? And he said, no, I 19 don't think they did. And then he said, the insert 20 and the PDR, which is the same thing as the insert, in 21 1993 did not raise the issue of potential suicide and 22 violence. That's his warning opinion. 23 My note was right after the afternoon break, 24 and that's all he said. He didn't say my criticism is 25 it's not good enough to put it down here. You have to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1620 1 put it up here. He didn't say that. He said that it 2 did not raise the issue of potential suicide or 3 violence, and I submit the insert absolutely, 4 without -- without any possibility of argument does 5 raise the issue of potential suicide and violence. 6 So based upon his opinion and the limitation, 7 the very limited opinion that he gave, didn't say it 8 had to be in the warning, didn't say it needed to be 9 in big black type or red type or whatever. He said it 10 did not raise the issue. And that, by the exhibit, 11 that is really stipulated to be the warning at the 12 time, that's not -- that is absolutely not correct. 13 THE COURT: Although, as Mr. Vickery 14 reiterated, that's raised with respect to the 15 different cause in Prozac. 16 MR. SEE: With respect, Your Honor, the section 17 down here, it says, "the adverse events temporally 18 associated with Prozac." 19 THE COURT: "That have been received since 20 market introduction and which may have no causal 21 relationship with the drug." 22 MR. SEE: Correct. That language, I submit, 23 based upon Dr. Shlensky's opinion that the insert did 24 not raise the issue of the potential for violence, 25 that language covers that. I don't have any note that PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1621 1 Dr. Shlensky said another word about it. That was his 2 criticism and that criticism is absolutely satisfied 3 in the insert. 4 THE COURT: Thank you. Well, I'm not going to 5 rule on this at this point. I want to read 6 Ms. Mangrum's epistle here first. 7 MS. MANGRUM: Thank you, Your Honor. 8 THE COURT: So I think we ought to go ahead and 9 proceed with Defendant Lilly's case. We'll take a 10 short break to allow the jury to come in. 11 (Whereupon, a recess was taken at 9:55 a.m.) 12 (Whereupon, the following proceedings were had 13 in open court in the presence of the jury.) 14 THE CLERK: Civil No. 95-00185 ACK, Susan K. 15 Forsyth, et al. versus Eli Lilly and Company, et al. 16 MR. VICKERY: Good morning, Your Honor. Andy 17 Vickery, Karen Barth, and Roy Chang for the Forsyths. 18 THE COURT: Good morning. 19 MR. SEE: Good morning, Your Honor. Andy See, 20 Michelle Mangrum, and Ed Burke for Eli Lilly and 21 Company. 22 THE COURT: Good morning. Good morning, ladies 23 and gentlemen of the jury. I apologize for the delay, 24 but there was something that we had to resolve. 25 Please proceed, Mr. Vickery. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1622 1 MR. VICKERY: Thank you, Your Honor. At this 2 time, Judge Kay, I would like to offer some responses 3 to both request for admissions and interrogatories and 4 would ask the Court to instruct the jury about the 5 nature of these and then permit me to read them. 6 THE COURT: The Court will instruct the jury 7 that these answers to interrogatories are coming in 8 only for a limited purpose. You may only consider 9 them as to whether -- or as to the fact that Lilly had 10 notice of what is contained in these answers. 11 MR. VICKERY: Thank you, Your Honor. 12 From Exhibit 173 Lilly was asked to admit the 13 following: Admit that on or about November 6, 1989, 14 during a tele-session telephone conference conducted 15 under the sponsorship of Defendant Eli Lilly and 16 Company and Dista Products, a doctor reported that 17 among patients he or she had treated with Prozac there 18 were a, quote, few people who have gotten so hyper on 19 the medication that they couldn't even sit still 20 during the day. 21 Lilly's response was that Lilly admits that the 22 reference document contains the following statement: 23 Quote, a few people who have gotten so hyper on the 24 medication they couldn't even sit still during the 25 day. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1623 1 Request No. 11 in that same set -- 2 MS. MANGRUM: Excuse me, Mr. Vickery. Your 3 Honor, there's also the addition that Lilly denies all 4 other aspects of this request as part of our response. 5 MR. VICKERY: Oh, okay. I'm sorry. I thought 6 Mr. See didn't want me to read that. That Lilly 7 denies all other aspects of this request. 8 In Request for Admission No. 11, Lilly was 9 asked to admit that on or about November 6, 1989, 10 during a tele-session telephone conference conducted 11 under the sponsorship of Defendant Eli Lilly and 12 Company and Dista Products, a doctor reported that 13 three female patients complained after starting to 14 take Prozac, quote, that their attention span was 15 interfered with. That they felt they couldn't 16 concentrate. They couldn't work. They couldn't carry 17 on conversations. 18 Lilly's response was Lilly admits that the 19 reference document contains the following statement: 20 That their attention span was interfered with, that 21 they felt they couldn't concentrate, they couldn't 22 work, they couldn't carry on conversations, and denies 23 the remaining allegations or requests. 24 No. 12, Lilly was asked to admit that on or 25 about November 6, 1989 during a tele-session telephone PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1624 1 conference conducted under the sponsorship of 2 Defendant Eli Lilly and Company and Dista Products, a 3 doctor reported, quote, I have had about three people 4 out of perhaps fifty who have taken Prozac that 5 complained of feeling quite hyper and nervous. 6 Lilly's response was that Lilly admits that the 7 reference document contains the following statement: 8 I have had about three people out of perhaps fifty who 9 have taken Prozac that complained of feeling quite 10 hyper and nervous. Lilly denies the remaining portion 11 of the request. 12 No. 13, Lilly was asked to admit that on or 13 about November 8, 1989, during a tele-session 14 telephone conference conducted under the sponsorship 15 of the Defendant Eli Lilly and Company and Dista 16 Products, a doctor reported, quote, I also suspect 17 that Prozac has an amphetamine-like action. 18 The response was that Lilly admits that the 19 reference document contains the following statement: 20 Quote, I suspect that Prozac has an amphetamine-like 21 action, end quote. And Lilly denies the remaining 22 portions of that request. 23 No. 14, Lilly was asked to admit that on or 24 about November 8, 1989 during a tele-session telephone 25 conference conducted under the sponsorship of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1625 1 Defendant Eli Lilly and Company and Dista Products, a 2 doctor reported that adverse effects reported by his 3 patients taking Prozac included, quote, severe anxiety 4 and the patient describing that they're about to jump 5 out of their skin. 6 Lilly's response was that Lilly admits that the 7 reference document contains the following statement: 8 Quote, severe anxiety and the patient describing 9 they're about to jump out of their skin. Lilly denies 10 the remaining portions of that request. 11 No. 18, Lilly was asked to admit that on or 12 about October 26, 1989 at 8:30 p.m. Eastern Daylight 13 Time during a tele-session telephone conference 14 conducted under the sponsorship of Defendant Eli Lilly 15 and Company and Dista Products, a doctor reported, 16 quote, I've had to stop Prozac with a number of 17 patients who just complained that they felt so 18 restless, almost akathisic, that they couldn't 19 tolerate it. 20 The response was Lilly admits that the 21 reference document contains the following statement: 22 Quote, I've had to stop Prozac with a number of 23 patients who just complained that they felt so 24 restless, almost akathisic, that they couldn't 25 tolerate it, end quote. Lilly denies the remaining PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1626 1 portions of that request. 2 No. 19, Lilly was asked to admit that on or 3 about October 26, 1989 at 8:30 p.m. Eastern Daylight 4 Time, during a tele-session telephone conference 5 conducted under the sponsorship of Defendant Eli Lilly 6 and Company and Dista Products, a doctor reported, 7 quote, my biggest problem as I said before, and I hope 8 someone will address this, is the question of 9 agitation. 10 The response was that Lilly admits that the 11 reference document contains the following statement: 12 Quote, my biggest problem, as I said before, and I 13 hope someone will address this, is the question of 14 agitation. Lilly denies the remaining portions of 15 that request. 16 No. 21, Lilly was asked to admit that on or 17 about October 25, 1989 during a tele-session telephone 18 conference conducted under the sponsorship of 19 Defendant Eli Lilly and Company and Dista Products, a 20 doctor reported when giving Prozac to schizo-affected 21 patients in a state hospital that, quote, we thought 22 Prozac might help activate them a little bit, and it 23 did activate them, but they started bopping other 24 people on the unit so we had to stop it. 25 Lilly's response was Lilly admits that the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1627 1 reference document contains the following statement: 2 Quote, we thought Prozac might help to activate them a 3 little bit and it did activate them, but they started 4 bopping other people on the unit so we had to stop it. 5 No. 24, Lilly was asked to admit that on or 6 about October 17, 1989 at a focus group held by or 7 under the auspices of Eli Lilly and Company, a doctor 8 reported that one side effect he had seen is, quote, 9 is the irritability. It, Prozac, just makes them feel 10 wired. 11 The response, Lilly admits that the reference 12 document contains the following statement: Is the 13 irritability. It, Prozac, just makes them feel wired. 14 Lilly denies the remaining portions of that request. 15 That's all from 173, Your Honor. From No. 174, 16 Lilly was asked to admit that Lilly cannot explain how 17 Prozac works either for the treatment of depression. 18 The response was that Lilly admits that 19 technology has not advanced to the point where it is 20 possible to measure serotonin at the level of the 21 synaptic cleft in the brain of a living human being, 22 but states that this mechanism has been observed at 23 work in animals. 24 From No. 178, No. 16, Lilly was asked to admit 25 that Prozac has an activating effect in some people. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1628 1 Lilly's response was, it is admitted that 2 Prozac has an activating effect in some patients, a 3 sedating effect in other patients, neither effect in 4 some patients, and both effects in some patients. 5 Number 20, Lilly was asked to admit that Lilly 6 relies not only on package inserts and other 7 literature, but also on direct communication, both via 8 mails and Lilly agents, sometimes called detailed men, 9 to apprise prescribing physicians of the risks, 10 indications, contraindications, and other pertinent 11 information on Prozac and other Lilly drugs. 12 The response was -- 13 THE COURT: Excuse me a minute. Is this one 14 that was to be read? 15 MR. VICKERY: Yes, it was, Your Honor. 16 MS. MANGRUM: We have no objection, Your Honor. 17 THE COURT: Very well. 18 MR. VICKERY: Lilly admits that it relies on 19 package inserts, medical and scientific literature, 20 direct mail and direct communications consistent with 21 its package inserts by sales representatives to 22 apprise prescribing physicians of the risks, 23 indications, contraindications and other pertinent 24 information of Prozac and other Lilly drugs. 25 That's all from No. 178. And finally, from No. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1629 1 176, Your Honor -- 2 THE COURT: From what number? 3 MR. VICKERY: 176. This is an interrogatory to 4 Lilly. 5 MS. MANGRUM: Wait just a moment, Your Honor. 6 MR. VICKERY: Yes, I can. No. 14. May I have 7 a moment, Your Honor? 8 THE COURT: Yes. 9 MR. VICKERY: No. 14, Lilly was asked the 10 following question: State the number of people known 11 to defendants that have killed another person or 12 persons while on Prozac, Fluoxetine hydrochloride. 13 Lilly's answer, Lilly states that based on 14 incomplete information and as a, quote, approximation, 15 that between March 1, 1983 and November 1992 it 16 reported to the FDA 88 events resulting in fatal 17 outcomes to persons other than patients undergoing 18 Prozac therapy. 19 Your Honor, that concludes our offer. We rest 20 our case. 21 THE COURT: Very well. Mr. See. 22 MR. SEE: Thank you, Your Honor. For its first 23 witness, Eli Lilly and Company will call Dr. Gary 24 Tollefson. 25 THE CLERK: Please raise your right hand. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1630 1 GARY DENNIS TOLLEFSON, M.D., 2 called as a witness on behalf of the Defendant, after 3 having been first duly sworn to tell the truth, the 4 whole truth, and nothing but the truth, was examined 5 and testified as follows: 6 THE CLERK: Please be seated. Please state 7 your name and spell your last name. 8 THE WITNESS: Gary Dennis Tollefson. Last name 9 is T-O-L-L-E-F-S-O-N. 10 DIRECT EXAMINATION 11 BY MR. SEE: 12 Q. Good morning, Dr. Tollefson. 13 A. Good morning. 14 Q. Are you a medical doctor, sir? 15 A. Yes, I am. 16 Q. Do you have a particular specialty? 17 A. Specialty is psychiatry and psychopharmacology. 18 Q. Where are you employed, sir? 19 A. At Eli Lilly and Company, Indianapolis, 20 Indiana. 21 Q. And what is your title? 22 A. I am the product group president for our 23 neurosciences division. 24 Q. And is the neurosciences division the division 25 at Eli Lilly and Company that is responsible for the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1631 1 antidepressant prescription drug called Prozac? 2 A. Yes, it is. 3 Q. Just a little bit about your background first, 4 Dr. Tollefson. First, would you tell the jury where 5 you come from? 6 A. I was born and raised in a small town called 7 Fairmont, Minnesota, and then I went to the University 8 of Minnesota as an undergraduate. Did my 9 undergraduate work in psychology, where I graduated 10 sum cum laude, and elected to stay on there because it 11 was close to home. Went to medical school also at the 12 University of Minnesota, and then after getting my 13 M.D., I received a Ph.D., a doctoral degree, in 14 pharmacology. Those were all at the University of 15 Minnesota. 16 Q. When did you graduate from college? 17 A. Graduated from college in 1973. 18 Q. And that was with a degree in psychology? 19 A. That's correct. 20 Q. And then medical school, what year did you 21 graduate from medical school? 22 A. 1976. 23 Q. Now, after your medical school, did you go on 24 for additional training as a physician? 25 A. Yes, I did. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1632 1 Q. Would you tell the jury about that, please? 2 A. I did one year of what we call a general 3 internship, which is an experience rotating through 4 different medical specialties; surgery, trauma, 5 pediatrics, neurology, et cetera, for a year, and then 6 I went into what we call a residency in psychiatry and 7 went through that psychiatry residency program in 8 three years at the University of Minnesota. 9 Q. Now, you mentioned having some additional 10 training in psychopharmacology? 11 A. That's correct. 12 Q. First, could you tell us what 13 psychopharmacology is? 14 A. Well, of course, pharmacology is the study of 15 drugs. Psychopharmacology implies the study of 16 medications or drugs that has an influence on the 17 central nervous system, more specifically, I guess I 18 would say, the human brain, so it's a subspecialty of 19 pharmacology. 20 Q. Now, you said you went on and had additional 21 formal education in psychopharmacology? 22 A. Yes, I did. 23 Q. Tell us what that was, please. 24 A. Sure. I did go forward and complete a Ph.D, 25 which is a doctoral degree outside of or in addition PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1633 1 to the medical degree, and it was a cross-disciplinary 2 program. It involved the school of pharmacology at 3 the University of Minnesota, also the School of 4 Biochemistry at Minnesota, and then the department of 5 psychiatry. 6 Q. Now, in your field of psychiatry, have you 7 become what is known as board certified? 8 A. Yes, I have. 9 Q. Could you briefly tell us what that is? 10 A. Board certification in a medical specialty is a 11 specific examination that is provided to physicians 12 that they can elect to take or not to take, and the 13 examination includes both a series of written 14 questions about the field of research and also an oral 15 examination by peers in the field that are already 16 board certified, and if the applicant passes both the 17 written and the oral examinations, if he or she is so 18 fortunate, then they are designated to be board 19 certified. So it is a process, I think, to endorse 20 the training and the knowledge base of the physician. 21 Q. When did you become board certified in 22 psychiatry? 23 A. That would have been, thinking back, probably 24 around 1981 or '2. 25 Q. Now, after you completed your Ph.D. program, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1634 1 did you then go on and seek employment somewhere? 2 A. I did. My internship, which I had mentioned to 3 you earlier, was at a county hospital, a trauma 4 hospital, and a hospital that provided care for all 5 types of patients in the St. Paul, Minnesota area, 6 called St. Paul Ramsey Medical Center, and I was 7 offered a position to stay on there in the department 8 of psychiatry in an area called consultation liaison 9 psychiatry, and what that is, quite briefly, is when a 10 medical physician, let's say an internist, might have 11 somebody in the coronary care unit or we had a burn 12 unit, a regional burn unit there, if the physician in 13 charge of patient care had a question about their 14 patient, about their psychiatric status or the use of 15 medications, whatever, consultation liaison 16 psychiatrist would be someone who would come in, 17 provide an opinion to the doctor, and help him to 18 manage or follow the case, so I started my career in 19 that area. 20 Q. All right. And did your responsibilities at 21 the St. Paul Ramsey Hospital change after a time? 22 A. It did after I was there approximately five 23 years, and during that time, I was involved also as an 24 assistant professor at that time at the University of 25 Minnesota Hospital, so I was doing teaching as well as PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1635 1 patient care and research. And about halfway through 2 my stint at Ramsey, about five years there, I became 3 the department chairperson, which is the -- 4 essentially, the administrative head of the 5 psychiatric practice group. 6 Q. After you became the chair of the department of 7 psychiatry, did you continue to see psychiatric 8 patients? 9 A. Yes, sir. 10 Q. Would you tell us about that, what kind of 11 patients you saw, and so on? 12 A. We really, at St. Paul Ramsey Medical Center 13 saw a very wide diversity of patients. We were at the 14 forefront in Minnesota of what you have heard of 15 called HMOs or the Health Maintenance Organizations. 16 We had a lot of patients that were members of those 17 programs. We had some satellite clinics so we saw 18 patients from the suburban areas that had traditional 19 insurances like the Blue Cross/Blue Shield programs, 20 but we were also a county-based facility, receiving 21 support from the county, so we would see indigent 22 patients, patients on a variety of government 23 programs. So particularly in the department of 24 psychiatry, we tended to see a lot of patients that 25 had very chronic mental disorders. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1636 1 Q. Can you give us an idea of the kind of mental 2 disorder that you had experience with during your 3 stint there at St. Paul Ramsey? 4 A. They would be typically what we would refer to 5 as the more major psychiatric conditions, 6 schizophrenia, manic depression, or what's called 7 bipolar disorder, you may have heard of, major 8 depression, some of the more serious anxiety 9 disorders. Also did a lot of work with Alzheimer's 10 disease and Parkinson's disease in the sense of 11 patients that might have behavioral or memory problems 12 associated with those disorders as well. So it was a 13 diversity of more serious kinds of neurologic or 14 psychiatric conditions. 15 Q. Dr. Tollefson, there's been testimony in the 16 case about medical and scientific publications in 17 peer-reviewed journals. Have you authored such 18 publications? 19 A. Yes, sir. 20 Q. Tell us how many. 21 A. Approximately 200 papers that have been in 22 peer-reviewed journals. 23 Q. And on what topics generally have you written 24 on? 25 A. Primarily in the area of drugs and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1637 1 psychopharmacology, but relevant to either depression 2 or psychosis, to a lesser extent, schizophrenia, 3 looking at issues of how drugs work or how drugs are 4 tolerated. 5 Q. Have you had publications in peer-reviewed 6 medical and scientific journals that dealt 7 specifically with research about Prozac? 8 A. Yes, I have. 9 Q. About how many such publications have you had 10 in that area? 11 A. I'd estimate approximately 15 to 20 that 12 specifically dealt with Prozac. 13 Q. In your career, have you been called upon to 14 give speeches and presentations on medical and 15 scientific issues to professional groups and 16 organizations? 17 A. I have. I have had the pleasure to be able to 18 speak internationally, prior to joining Lilly, as a 19 senior academic member of the community and presenting 20 research and particularly being involved in physician 21 education programs. They're called continuing medical 22 education activities, and then since being with Lilly, 23 still involved very much in the academic community 24 with the international meetings, but also doing a lot 25 of things, even at a local level with community-based PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1638 1 physicians because they're the people always in the 2 trenches. 3 Q. Now, at some time, you made a decision to leave 4 the St. Paul Ramsey Hospital and go to work for Eli 5 Lilly and Company? 6 A. That's correct. 7 Q. When was that, please? 8 A. 1991, the middle of the year. 9 Q. What prompted that decision? 10 A. Well, as I mentioned, I had been involved in 11 doing medical education and training programs, some of 12 those sponsored by a variety of different 13 pharmaceutical companies, and I had had a very 14 positive experience interacting with people at Eli 15 Lilly and Company as far as their integrity, their 16 interests in education. I then became involved in 17 consulting with the company, along with some 18 colleagues of mine from academia, on the whole issue 19 of antidepressant medications and symptoms of 20 depression, including suicidal ideation or suicidal 21 attempts, and through that consultation process, I'd 22 been very impressed with the level of scientific 23 integrity of the company. I think they, in turn, 24 appreciated the scientific thinking that I was able to 25 bring, and they were kind enough to offer me a job, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1639 1 and after I thought long and hard to leave Minnesota, 2 I decided that it was an appropriate time in my career 3 to try something different and to make a different 4 kind of impact in medicine, and so I accepted it. 5 Q. And you've been with Lilly ever since? 6 A. That's correct. 7 Q. Can you tell us just generally what have been 8 your responsibilities with the company? 9 A. Well, I joined the company initially in a 10 position that's called an executive director in the 11 company's medical division, and I was overseeing the 12 area, again, of psychopharmacology and did that for 13 two or three years. 14 At that point, the company promoted me to a 15 vice president within the medical division, and about 16 that time, we began developing a very interesting new 17 medication for schizophrenia, and I had the pleasure 18 of leading a cross-functional team to bring that drug 19 through its final stages of development and into the 20 marketplace. And then more recently, about a year 21 ago, I was promoted to president of the neurosciences 22 product group. 23 Q. Dr. Tollefson, during your career, both when 24 you were in academic medicine and during the time you 25 have been at Lilly, have you personally been involved PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1640 1 in performing clinical research studies using drugs 2 with humans? 3 A. Yes, I have. 4 Q. How many -- just approximately, how many 5 clinical trials have you personally been involved 6 with? 7 A. Since I've been at Eli Lilly and Company? 8 Q. Both before and after. 9 A. Well, I would say it's certainly in excess of 10 100, probably closer to 200 trials. 11 MR. SEE: Your Honor, at this time, Eli Lilly 12 and Company would tender Dr. Tollefson as an expert in 13 psychiatry and in psychopharmacology. 14 MR. VICKERY: Your Honor, Dr. Tollefson is 15 clearly qualified by education and experience to 16 render opinion testimony within the meaning of Rule 17 702. 18 THE COURT: Thank you. The Court finds 19 Dr. Tollefson qualified as an expert in the area of 20 psychiatry and psychopharmacology. 21 Q (By Mr. See) Now, Dr. Tollefson, this case, 22 as you know, involves the disease, major depression. 23 I take it, during your career, you have had experience 24 in diagnosing and treating patients with that 25 condition? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1641 1 A. Very frequently. 2 Q. Doctor, is suicide one of the risks and one of 3 the possible outcomes of the disease, major 4 depression? 5 A. Well, it is, but I'd even say more so, it is 6 one of the diagnostic symptoms that we look for in 7 reaching the diagnosis of major depression. It's one 8 of the nine critical symptoms that one would observe 9 in order to make the diagnosis. 10 Q. Now, Doctor, we've heard some testimony in the 11 case that suicide is a relatively rare event, and I 12 want to ask you some questions about that, but first 13 has a chart been prepared that would help illustrate 14 your testimony on that point? 15 A. Yes, sir. 16 Q. Let me put up Defendant's Exhibit 1080, and, 17 Doctor, if you'll look in the notebook that's right 18 next to you, there will be a small copy of this at Tab 19 34, so you can see it along with the jury. 20 A. I have it. 21 Q. Now, first of all, the chart indicates that in 22 1993, which is the date -- the year of the deaths of 23 Mr. and Mrs. Forsyth, that there were 31,102 suicides 24 in the United States. Could you tell us, how does 25 suicide rank in 1993 as the cause of death in this PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1642 1 country? 2 A. Well, as the jurors can see in the second 3 point, it was in the top ten. It was the ninth 4 leading cause of death in the U.S. 5 Q. And what does the suicide rate look like when 6 you look specifically at white males who were 55 to 64 7 years old, what does that rate look like? 8 A. Well, it shows that there is an increased risk, 9 and as you can see, the figure goes to 25.7 instances 10 per 100,000 individuals, so slightly more than a 11 doubling. 12 Q. Now, is that 25.7 per 100,000, does that 13 concern depressed people? 14 A. No. That's just a general figure for 15 individuals across our entire population, but within 16 that age bracket. 17 Q. Now, could you also tell the jury, when you 18 look at persons of the male gender only, what 19 percentage of suicides are involved in people who are 20 males? 21 A. Males commit four out of every five suicides in 22 the U.S. 23 Q. Now, in your work, in your career, you're 24 familiar with medications that had been developed to 25 treat major depression? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1643 1 A. Yes, sir. 2 Q. And we've had some testimony in this case about 3 tricyclic antidepressants or abbreviated as TCAs. Are 4 you familiar with that group? 5 A. Yes, I am. 6 Q. Now, Dr. Tollefson, would you tell the jury, 7 please, with respect to using tricyclic 8 antidepressants in depressed patients who may be 9 suicidal, is there any particular risk of those 10 medications? 11 A. Well, there are two related risks that are 12 really quite significant, and which why, I think, 13 explain why, in general, these tricyclics or TCAs have 14 become less and less popular with physicians. Number 15 one, they require significant dose escalation or dose 16 titration, which means starting low with a small dose 17 and needing to work up. 18 The literature, our medical literature is quite 19 replete that all too often, patients cannot tolerate a 20 necessary dose to treat their depression with these 21 older drugs because they have so many side effects, so 22 they don't receive what we call a therapeutic dose of 23 the medicine, but even more importantly, they are 24 highly toxic in an overdose, so you're confronted with 25 a patient that might have a risk of suicide as part of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1644 1 depression who now, at least historically in the past, 2 you had to give a medication where, if they consumed 3 five, six, seven days' worth, just a week's worth of 4 their prescription, it could be enough to kill them. 5 And so with the introduction of newer 6 medications, it had a much wider margin of safety. Of 7 course, physicians could be much more comfortable and 8 effectively and aggressively trying to treat this very 9 serious disease. 10 Q. All right. Now, let's turn to the development 11 of Prozac, Dr. Tollefson, and again, is there a 12 graphic chart that we prepared that would help 13 illustrate your testimony -- 14 A. Yes. 15 Q. -- on the development of the drug? 16 A. Yes, there is. 17 THE COURT: What's the number on that? 18 MR. SEE: That is Exhibit 1077, Your Honor. 19 THE COURT: Thank you. 20 Q (By Mr. See) I'll put it up on the easle, 21 Doctor, and if you would turn -- if you would turn in 22 your book to Tab 35, there's a small copy there that 23 you can refer to. 24 A. I have it. 25 Q. First, on the chart we're looking at, there's a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1645 1 word called synthesis. What's that mean? 2 A. Synthesis is a term that we would use relative 3 to the chemical process of manufacturing the 4 medication, so it undergoes a process of being 5 synthesized. 6 Q. All right. Can you tell us what year was 7 Prozac actually discovered, the compound? 8 A. 1972. 9 Q. Now, we've heard a little testimony about how 10 Prozac works, and I'd like to ask you if you could 11 tell the jury, briefly and in lay language that we 12 will be able to understand, how does Prozac work? 13 A. Well, I'll do my best. Maybe just as a 14 preface, the older antidepressants that we referred to 15 as the tricyclic antidepressants or the TCAs, I 16 mentioned that they had a very large number of side 17 effects that were often problematic for patients, one 18 of the reasons for that is that those medications 19 affected many different chemical sites within the 20 brain, and Prozac and its family of medications that 21 are called selective serotonin uptake inhibitors. The 22 term "selective" means that they're targeted just for 23 one site, a serotonin-based site in the brain. 24 Q. I want to stop you there for a second. You 25 used the phrase, selective serotonin reuptake PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1646 1 inhibitor. Is that abbreviated SSRI? 2 A. Yes, it is. 3 Q. And is that the family of antidepressant 4 medications that Prozac belongs to? 5 A. Yes, it is. 6 Q. And there are others that belong to that family 7 now? 8 A. That is correct. 9 Q. Okay. Would you go on, please? 10 A. Sure. So with the specific targeting that this 11 medication has, it goes to a site in the human brain. 12 And remember, the brain is comprised of literally 13 billions and billions of nerve cells, and those nerve 14 cells have a site on them where serotonin, which is a 15 chemical messenger, a way of communicating from one 16 cell to its neighbor, they go specifically -- a drug 17 like Prozac -- to this, what's called, reuptake site, 18 a place where the brain chemical goes back up into the 19 nerve cell. 20 And, essentially, this class of medications 21 blocks that site. It doesn't allow serotonin, the 22 chemical, to go back into that nerve cell, which means 23 more of it is around in the area between the two nerve 24 cells to continue the communicating process. And it's 25 our belief in the field of psychiatry that one of the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1647 1 factors that contributes to the biological, the 2 medical aspect of depression, is, relatively speaking 3 having too little serotonin. So by blocking, it's 4 being taken back up into cells where it would be 5 destroyed or stored, but not able to be an effective 6 communicator. A drug like Prozac keeps more of the 7 serotonin in that area so it can continue to 8 communicate, so it's making up, essentially, for a net 9 deficit or a shortage of that chemical during an 10 episode of what we call major depression. 11 Q. Doctor, what prevents their being too much 12 serotonin in this area of the brain that you're 13 talking about? 14 A. Well, of course, the human body is a very 15 marvelous organism and it has checks and balances in 16 how the body works, and one of those examples of a 17 balance system is that same nerve cell also has some 18 receptors on its external surface that are sensitive 19 to monitoring how much serotonin is out there, and if 20 you began to have an increase in serotonin, those 21 sensors would send off a signal and they would tell 22 that nerve cell to stop releasing serotonin into that 23 area again of communication we call synaptic clef. 24 And the origin of serotonin, we've talked a 25 little bit about that and it may seem like a bit of a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1648 1 foreign term, serotonin, this brain chemical 2 actually -- its origin is from dietary amino acids, 3 and specifically an amino acid we call tryptophan; 4 that when we eat foods that have tryptophan in them, 5 it is converted in the body, this chemical serotonin, 6 and it's stored in these particular nerve cells and it 7 can be released then with an appropriate signal within 8 the brain. 9 Q. Now, coming back to our chart on drug 10 development. First, there's indicated that there's a 11 process in the chemical lab. What happens there? 12 A. From the chemical lab, basically, we're going 13 from that early stage of having synthesized or created 14 this particular chemical, and what we do is we 15 continue to try to refine it and understand more about 16 its chemical properties. 17 Q. There then is the phase called pharmacology or 18 toxicology. Is that the phase when studies with 19 animals are done? 20 A. That is correct. 21 Q. And why are studies with animals done? 22 A. Well, initially, it's important, with the new 23 medication, to characterize it in several different 24 ways. We call it pharmacology. What we're really 25 talking about are four areas of understanding the drug PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1649 1 and they're sometimes called ADME. I can briefly tell 2 you what those are. One is, is the drug absorbed, 3 that's A, and, of course, if you're going to take a 4 medication orally, it's important that it gets 5 absorbed and gets into the system. 6 Number two, D is the disposition of the 7 medication. Where does it go in the body and at what 8 rates does it go into those areas of the body? M is 9 the metabolism. How is the medication broken down by 10 the body and ultimately cleared from the body, through 11 the kidneys, through the liver, a combination of both. 12 And then that last stage is the E, that's the actual 13 excretion, the actual route that the drug leaves the 14 human body. 15 Q. Now, there's a label on our chart called IND 16 filing. Can you tell us, please, what is an IND? 17 A. When a pharmaceutical company has a drug that 18 they believe is a promising candidate to be evaluated 19 for a health care problem, and they've done this 20 preliminary toxicology and pharmacology, it is 21 necessary to file this particular drug with, in the 22 case of the U.S., the Food and Drug Administration, 23 and you are, essentially, filing that you have an 24 investigational drug, this is what you know about it, 25 and you then wait for the FDA, essentially, to review PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1650 1 that and give you a thumbs up that it's okay to begin 2 to move further on in the drug development process. 3 Q. So IND stands for Investigational New Drug? 4 A. Yes. 5 Q. And is that the application filed with the FDA 6 before the actual studies with human beings start? 7 A. Yes, it is. 8 Q. And when was that filed with Prozac? 9 A. It was approximately 1976, I believe. 10 Q. Now, we now have it in, the yellow indication 11 on the chart, a bunch of phases. 12 A. Um-hum. 13 Q. Tell us, what is phase one? 14 A. Well, phase one is moving into -- it's, 15 essentially, a replication of what we just talked 16 about, the pharmacology, but is now done in humans, so 17 we replicate and try to understand exactly, again, how 18 is the drug absorbed, distributed, metabolized, and 19 excreted within humans. There also is the opportunity 20 to observe any general properties of that medication. 21 These are typically done in volunteers, not in 22 patients with a particular disease state in phase one. 23 Q. Now, tell us, what is the involvement of the 24 FDA when clinical studies; that is, studies in human 25 beings are going on? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1651 1 A. The FDA is, of course, constantly interested 2 and vigilant for what is going on and it's necessary 3 for pharmaceutical sponsors to provide periodic 4 updates as to the progress of that work, and so it's 5 undergoing, really, constant scrutiny and observation 6 by the agency. 7 Q. In other words, if you do a study in phase one, 8 do the results get sent to the FDA? 9 A. Yes, sir. 10 Q. Now, tell us about phase two. What happens 11 there? 12 A. Phase two is typically when you begin to move 13 into patients that might have a disease state, so you 14 could be studying a drug, let's say, for cancer or for 15 diabetes. You'd now begin to test the properties of 16 that drug in treating the disease of interest, and 17 those studies are designed to look at two things: 18 One, is the medication efficacious? Does it work? 19 How well does it work? And on what features of the 20 disease is it working? 21 And then there's also a phase, of course, 22 evaluation of the safety of the medication, what kind 23 of side effects might someone have? How severe are 24 they? How well tolerated is the medication relative 25 to a comparator, a comparison? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1652 1 Q. With the case of Prozac, a drug that was 2 intended to treat depression, what kind of patients 3 are involved in the studies in phase two? 4 A. These were patients almost exclusively who met 5 the criterion for what we call a major depressive 6 episode. 7 Q. Now, the studies done during phase two, are 8 those results sent to the FDA? 9 A. Yes. 10 Q. Now, we have phase three. What happens in 11 phase three? 12 A. Phase three is an effort to expand into much 13 larger patient samples and -- 14 Q. What is a patient sample? 15 A. I'm sorry. A group of patients that have the 16 disease, and -- in phase three, so number one, the 17 number of study participants or patients with the 18 illness is much larger and there's an effort to go 19 into more diversities of individuals to look at the 20 benefits and the safety or tolerability of a 21 medication based on age, gender, ethnicity, all those 22 relevant factors that reflect the diversity of our 23 society. 24 Q. Now, there's a point here on the chart that's 25 called NDA submission. First tell us, what does NDA PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1653 1 mean? 2 A. NDA is a term that stands for a New Drug 3 Application. 4 Q. What is that? 5 A. It's a very laborious task of collecting 6 clinical reports from all of the preclinical phase 7 one, phase two, phase three experiences with the 8 medication, complying it into multiple, multiple 9 volumes and submitting that to the Food and Drug 10 Administration in the case of the United States, 11 requesting their evaluation of whether or not they 12 find, based on your data, that the drug is both safe 13 and effective for the proposed indication. 14 Q. So is it the case that when the NDA is 15 submitted, the data from all of the studies that had 16 been done to date are submitted to the FDA at one 17 time? 18 A. There is, indeed, a summary of all information. 19 Q. And with Prozac, was there an NDA filed? 20 A. Yes, there was. 21 Q. And when was that done, sir? 22 A. I believe it was in about 1983. 23 Q. Now, after the NDA is filed, does the research 24 stop? 25 A. Absolutely not. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1654 1 Q. What goes on? 2 A. One would continue to do a variety of clinical 3 studies with the medication. We work very closely, 4 for example, with academic medical centers and with 5 leading people in the field to continue to look at 6 what would be some of the scientific questions that 7 they might have about the medication, about the 8 disease state. Obviously, medical technology is going 9 leaps and bounds every year, and so there are new 10 technologies that we can employ in the study of 11 medication, so it's a constant iterative-like learning 12 process that goes on throughout the life cycle of a 13 product. 14 Q. Now, when all of this information on these 15 studies is submitted to the FDA, what does the FDA do 16 with it? 17 A. Well, the FDA spends significant amounts of 18 time reviewing those application materials in great 19 depth. They have many different components that would 20 review it. They have toxicology reviewers. They have 21 what are called biostatisticians, people that look at 22 all the numbers. They have clinicians that review the 23 materials, and so there's a fairly long extensive 24 process of reviewing the materials, generating 25 potential questions, sharing those questions with the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1655 1 company or the sponsor. There is a dialog of back and 2 forth in trying to understand and really fully 3 characterize the profile of what that data means. 4 Q. Did there come a time when the NDA for Prozac 5 was approved by the FDA? 6 A. Yes. 7 Q. When was that, please? 8 A. That was in December of 1987 in the U.S. 9 Q. So the FDA took, what, about four years or so, 10 four or five years -- 11 A. Yes. 12 Q. -- to review the information that was 13 submitted? 14 A. That is correct. 15 Q. Now, what does it mean when the NDA gets 16 approved? What happens? 17 A. When the NDA is improved, that means now that 18 the company has authorization to begin to market that 19 product for the treatment of the specific disorder 20 that was applied for. So in the case of Prozac, for 21 the treatment of major depression. 22 Q. So Prozac began to become available for doctors 23 to prescribe to their patients, and you said the 24 approval was in December of '87, so it was '88 -- 25 A. I believe it was January of '88. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1656 1 Q. Now, there's one last element on the chart 2 here. It says, "Post-approval phase four." Tell us 3 what that means. 4 A. Well, post-approval means the NDA has been 5 approved by the FDA; that is, they have found the drug 6 to be both safe and effective for treatment of the 7 disorder. So it's post-approval activities, and those 8 clinical studies, again, as I alluded to earlier, 9 would be the ongoing investigation of interest, both 10 of the company and the academic community, and the 11 exploration of further properties of the medication, 12 how it can be used in the treatment of either the 13 disorder that's already been approved, in other words, 14 additional studies in depression, or in the case of 15 Prozac and many other medications, other possible new 16 indications that one might look at. 17 Q. Dr. Tollefson, I want to ask you about the 18 clinical studies done by Lilly during the development 19 of Prozac. Have we prepared another chart that shows 20 that? 21 A. Yes, sir. 22 MR. SEE: Your Honor, this is Exhibit 1089. 23 THE COURT: Thank you. 24 Q (By Mr. See) Dr. Tollefson, I think a small 25 copy of this one is in your book at 36. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1657 1 A. A very small one. 2 Q. First of all, can you tell us what this 3 represents generally? 4 A. Yes. This is really looking at a chronology of 5 the studies that were going on from the earliest, sort 6 of phase one, phase two work that we mentioned, out 7 throughout continued development of this product, and 8 it goes out through, if I can read this properly, 9 through 1996. 10 Now, of course, that work is continuing to go 11 on, but it's, I think, designed to try to portray both 12 the breadth and depth of clinical work that went into 13 the document, first of all, that the FDA reviewed, and 14 then secondly, points to the continued post-approval 15 or phase four work that is ongoing with this molecule. 16 Q. So each of the sort of orange lines represents 17 a study? 18 A. Each of these orange bars represents a specific 19 study protocol, and to your left would be the point 20 when the first patient was enrolled in the trial, and 21 to your right, the end of the orange bar, would 22 represent the last patient visit in an individual 23 protocol. So the sum total of the protocols would be 24 the number of horizontal bars you see. 25 Q. So it appears as if there are smaller and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1658 1 shorter clinical trials starting here around 1976, and 2 then clinical trials ongoing right on through 1996; is 3 that right? 4 A. That is correct. 5 Q. And did you say there are clinical trials being 6 sponsored or performed by Lilly that are going on 7 beyond that date? 8 A. Yes, there are. 9 Q. Are there clinical trials of Prozac being 10 sponsored by Lilly going on right now? 11 A. Yes, there are. 12 Q. Why is that? 13 A. Well, as I mentioned earlier, this particular 14 molecule really has the potential to treat a number of 15 other indications, and I think some of you that may 16 have, you know, followed a little bit about the 17 history of Prozac, know it was approved in the U.S. 18 for an eating disorder that often affects adolescents 19 called bulimia. It also has been approved for 20 obsessive compulsive disorder, and we're continuing to 21 pursue some other very interesting, serious clinical 22 problems where we think this drug could really help 23 people. 24 Q. And is it correct that there are ongoing 25 clinical trials that also deal with patients who have PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1659 1 major depression? 2 A. Oh, absolutely. 3 Q. Now, I would also like you to tell the jury 4 about the numbers of patients involved and the number 5 of clinical trials involved with patients with 6 depression, and is there another chart that has been 7 prepared that will help you illustrate that? 8 A. Yes. 9 MR. SEE: This, Your Honor, is 1088. 10 THE COURT: Thank you. 11 MR. VICKERY: May I have a question on voir 12 dire about this, Your Honor? 13 MR. SEE: It is the small one at Tab 37 of your 14 book, Doctor. 15 THE WITNESS: Thank you. 16 THE COURT: You may. 17 MR. VICKERY: Dr. Tollefson, are all of these 18 trials here in depressed people or are some of them in 19 people who are not depressed? 20 THE WITNESS: These trials would include 21 patients with depression and may well include people 22 that have other psychiatric disorders or we call them 23 co-morbidities with depression. 24 MR. VICKERY: Okay. So your testimony is not 25 limited to just depressed patients; is that right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1660 1 THE WITNESS: Correct. 2 MR. VICKERY: Okay. Very well. 3 Q (By Mr. See) Have you got the small one? 4 A. I do. 5 Q. Now, first it indicates number of worldwide 6 protocols. First, tell us what a protocol is. 7 A. A protocol is a written document that, 8 essentially, summarizes the purpose of a study, how 9 the study should be conducted, how the study will be 10 analyzed statistically, and then really what are the 11 primary reasons for the study to be done, so it's a 12 summary document. 13 Q. All right. And then it says, length of 14 exposure -- well, first of all, the number of studies 15 designed, that's 504? 16 A. Correct. 17 Q. Then length of exposure, what does that mean? 18 A. This would be how many -- the range of days or 19 years that a patient was actually exposed to the study 20 medication. 21 Q. Okay. And that would be anywhere from a day to 22 over a year in the Prozac study? 23 A. Correct. 24 Q. And then it says, "Number of investigators 25 participating in clinical trials worldwide," and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1661 1 that's listed at more than 1200. First, would you 2 tell us what does "investigator" mean? 3 A. An investigator would be a health care 4 professional, more often than not in these cases, a 5 psychiatrist who would be charged with carrying out 6 the protocol at his or her research site at a hospital 7 or medical center. 8 Q. Then we have a number of patients in the 9 worldwide clinical trial and that's more than 51,000, 10 and the number of Prozac patients listed is more than 11 27,000, and does that number indicate the number of 12 patients that actually took Prozac during the clinical 13 trials sponsored by Lilly? 14 A. The latter number, 27,000, does. 15 Q. Now, Dr. Tollefson, a stipulation was read to 16 the jury earlier that patients who had a current high 17 risk for suicide were excluded from outpatient studies 18 of Prozac. The stipulation also said that neither the 19 plaintiffs' experts nor the defense experts criticized 20 that, but I want to ask you about it. 21 Does that mean that patients who had suicidal 22 thinking or who had a history of suicide attempts were 23 excluded from the studies with Prozac? 24 A. No, it does not. 25 Q. Would you explain that to us? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 1662 1 A. First of all, if I could provide a little 2 background on it. Many of these protocols, but not 3 all, eliminated patients that were defined by having 4 a, quote, serious suicidal risk. That degree of 5 seriousness was at the discretion of the physician, 6 the investigator, to make the decision whether or not 7 the patient wa