2240 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 2,240 - 2,413 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 Wednesday, March 24, 1999 at 9:10 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 2241 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 2242 1 I N D E X 2 WITNESSES ON BEHALF OF DEFENDANT 3 VICTOR R. REUS, M.D., Ph.D. PAGE 4 Cross-Examination (Cont'd) by Mr. Vickery 2255 Redirect Examination by Mr. See 2346 5 Recross-Examination by Mr. Vickery 2357 6 BYRON A. ELIASHOF, Ph.D. 7 Direct Examination by Mr. See 2360 Cross-Examination by Mr. Vickery 2371 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 2243 1 (Whereupon, the following proceedings were had 2 in open court out of the presence of the jury.) 3 THE CLERK: Civil No. 95-00185ACK, Susan K. 4 Forsyth, et al. versus Eli Lilly and Company, et al. 5 MR. VICKERY: Good morning, Your Honor. Andy 6 Vickery, Karen Barth, and Roy Chang for the 7 Plaintiffs. 8 THE COURT: Good morning. 9 MR. SEE: Good morning, Your Honor. Andy See, 10 Michelle Mangrum, and Ed Burke for Eli Lilly and 11 Company. 12 THE COURT: Good morning. Mr. Vickery. 13 MR. VICKERY: Yes, Your Honor. I had just 14 mentioned two things to counsel for Lilly and to the 15 Court's law clerk this morning. There are two matters 16 that I would like to go into and didn't want to do so 17 in front of the jury in light of the Court's previous 18 rulings without either approaching the bench at side 19 bar or bringing it to your attention beforehand one 20 is, in light of Dr. Matthews' testimony, I would 21 like -- 22 THE COURT: We're on Reus now. 23 MR. VICKERY: I understand we are, but a door 24 has been opened by Dr. Matthews' testimony that I want 25 to cross-examine Dr. Reus about and that door is the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2244 1 German warning. The Court initially admitted the 2 German ruling, then Mr. See moved to strike the German 3 warning on the representation that there was nothing 4 in this case -- that it didn't fit this case, that 5 because the German warning was fully complied with in 6 this case, then it just didn't fit. 7 Now, I agreed at that time on Mr. See's 8 representation because I, quite frankly, thought that 9 he must have decided, as a tactical measure at that 10 time, to jettison Dr. Matthews, and that's the reason 11 I agreed to withdraw that exhibit, because 12 Dr. Matthews clearly says that two substantial factors 13 in the deaths of William and June Forsyth were, number 14 one, premature release from the hospital, and number 15 two, no more Xanax. So that opens the door to the 16 German warning. And since this gentleman, Dr. Reus, 17 has testified that the warnings are acceptable, I 18 think it is appropriate to cross-examine him with the 19 fact that different warnings are given in Germany than 20 in the United States, and they are warnings directed 21 to the very issues that Lilly's other expert, 22 Dr. Matthews, addressed. 23 THE COURT: I don't see how premature release 24 from a hospital and no more Xanax opens the door. 25 MR. VICKERY: Those are the very things the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2245 1 German warning warns physicians about, Judge. Those 2 are the exact things. They said, give concomitant 3 medications -- 4 THE COURT: And wasn't concomitant medication 5 given in this case, Inderal? 6 MR. VICKERY: The Xanax is a benzodiazepine, 7 Judge. That is what the Lilly investigators gave 8 during the clinical trials. And the German warning, 9 had it been given here, had it been heeded here, might 10 have resulted, and likely would have resulted, in them 11 continuing the Xanax which, as Dr. Matthews said, 12 would have provided a measure of protection. So yes, 13 there were other things given, but that still doesn't 14 cure the fact that Lilly's own expert says that no 15 more Xanax was a substantial factor in these deaths. 16 THE COURT: Dr. Neal testified that Inderal 17 would have taken care of any problem with akathisia. 18 Your witness. 19 MR. VICKERY: He's my witness in the sense that 20 he's a fact witness, Your Honor, and I had to call 21 him, but I can impeach any witness, including one that 22 I call. I think -- you see, I agree with 23 Dr. Matthews, that Xanax would have been necessary. 24 THE COURT: Pardon me? 25 MR. VICKERY: I happen to agree with Lilly's PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2246 1 expert on this, Dr. Matthews, that Xanax would have 2 provided a measure of protection that may well have 3 saved the Forsyth's lives, and all I'm saying to the 4 Court is that in view of the fact that Lilly warned 5 people in Germany about that and not in this country 6 about it, that the door is open now to put that 7 warning in and to cross-examine Dr. Reus with 8 respect -- 9 THE COURT: Didn't you cross-examine 10 Dr. Matthews? 11 MR. VICKERY: Well, Dr. Matthews is gone, Your 12 Honor. 13 THE COURT: I said, didn't you cross-examine 14 Dr. Matthews? 15 MR. VICKERY: Not on that point. 16 THE COURT: Why not? 17 MR. VICKERY: Because I was waiting for 18 Dr. Reus. 19 THE COURT: I thought you said he opened the 20 door. 21 MR. VICKERY: He did open the door. 22 THE COURT: Then why didn't you take advantage 23 of it? 24 MR. VICKERY: I made a tactical decision to 25 wait for this witness, who I already knew was going to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2247 1 testify about labeling. This witness testified about 2 labeling as well, Judge. It was a tactical decision 3 by counsel. A door's open, when do I go through it? 4 THE COURT: What's your proffer as to the 5 distinction between taking Xanax and Inderal? 6 MR. VICKERY: Well, Xanax is a benzodiazepine. 7 I'm not sure if Inderal is or not, but I'd like to 8 visit with Dr. Reus. 9 THE COURT: Well, you better find out before 10 you make your proffer. What's the difference? 11 MR. VICKERY: I want to know what this 12 gentleman says is the difference. 13 THE COURT: I want you to make a proffer. You 14 go ask your expert. 15 MR. VICKERY: Okay. You want me to do that 16 right now? 17 THE COURT: Great. 18 MR. VICKERY: Inderal is a beta blocker, Your 19 Honor. Xanax is a benzodiazepine. Benzodiazepines 20 were given by Lilly in the clinical trials. That's my 21 proffer. 22 THE COURT: What's the difference? 23 MR. VICKERY: Well, the difference of 24 significance to me is that the very drug that Lilly 25 allowed clinical investigators to use to mask these PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2248 1 symptoms in the clinical trial is the very class of 2 drugs that was being given that was discontinued. 3 That's the difference to me. 4 THE COURT: What's the difference in the effect 5 of the drug? 6 MR. VICKERY: I don't know that. I don't know 7 that, but this witness certainly does. 8 THE COURT: This is very significant to your 9 case, isn't it? 10 MR. VICKERY: I think that what's significant 11 to my case, Your Honor, is that Lilly gave a different 12 warning in Germany than they gave in this country. 13 THE COURT: If the drugs have the same effect, 14 then the impact is no different whether they gave the 15 warning or not. 16 MR. VICKERY: If he wants to say that, he can, 17 Judge, but that puts him conflicting with Lilly's 18 other expert, you see, and that creates a jury 19 question. The jury has heard -- 20 THE COURT: You're not even educating the jury 21 or the Court as to what the difference is. 22 MR. VICKERY: I'll tell you the difference. 23 The difference to me is if you have two Lilly experts 24 saying two different things, that that affects the 25 credibility of Lilly's case. I'm not a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2249 1 pharmacologist, but I'm smart enough to know that if 2 Lilly was given benzodiazepines in the clinical 3 trials, and that this man was taking a benzodiazepine, 4 and if it was discontinued by a physician who was not 5 properly warned, who was not warned as physicians were 6 in Germany, that that is information that is valuable 7 for the jury. That's the reason. 8 THE COURT: Why is it valuable if the drugs 9 have no different affect? 10 MR. VICKERY: To answer that, Your Honor, you 11 have to -- it's valuable -- 12 THE COURT: There ought to be a very simple, 13 obvious answer. 14 MR. VICKERY: Well, the simple, obvious answer 15 is if two Lilly witnesses are testifying in conflict 16 with one another, then that tends to diminish the 17 credibility of one of them. That's the answer to me. 18 THE COURT: And that's already happened, hasn't 19 it? 20 MR. VICKERY: Not yet on this issue. I haven't 21 asked Dr. Reus about this issue. 22 THE COURT: About what issue? 23 MR. VICKERY: About the German warnings and 24 about the Xanax, the discontinuation of Xanax. 25 THE COURT: As far as any other inconsistency, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2250 1 that's already happened in their testimony. 2 MR. VICKERY: No, Your Honor, it hasn't. I 3 haven't asked him. 4 THE COURT: I thought you just said that there 5 had been an inconsistency in the testimony of two of 6 Lilly's witnesses. 7 MR. VICKERY: I said that I haven't asked this 8 man the question. I don't know what his answer will 9 be. His answer may be consistent with the others. 10 THE COURT: You're not addressing my question, 11 Mr. Vickery. 12 MR. VICKERY: I'm sorry, Your Honor. I'm just 13 dense. I don't understand the Court's question. 14 THE COURT: I thought the point you were trying 15 to make was that the credibility of the Lilly 16 witnesses might be tarnished because they testified 17 inconsistently. Was that not your point? 18 MR. VICKERY: My point is that the credibility 19 would be tarnished if, in answer to the question I 20 want to ask this gentleman, he gives a different 21 answer from the other Lilly witness. 22 Now, so in that case, you have two Lilly 23 witnesses that are giving contradictory answers, that 24 affects their credibility. If, on the other hand, he 25 gives the same answer as the other Lilly witness, then PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2251 1 we have a conflict between what Lilly warned in 2 Germany and what its witnesses are saying in this 3 case. In either instance, regardless of the answer 4 Dr. Reus gives to the question, there is a conflict 5 between Lilly's position and that affects their 6 credibility. That's why I brought it up. That's my 7 offer. 8 THE COURT: And my point was that the conflict 9 has already been made if you're correct. One has 10 testified one way. One has testified the other way. 11 MR. VICKERY: No, Your Honor, with respect, 12 Dr. Reus has not been asked about either German 13 warnings or the discontinuation of Xanax. That's what 14 I want to do, but I didn't want to do it in front of 15 the jury and I didn't want to take up a lot of time at 16 side bar. That's the reason I asked to visit with the 17 Court about it first. 18 THE COURT: Mr. See. 19 MR. SEE: Your Honor, the German warning, which 20 was withdrawn by the plaintiffs, says nothing about 21 benzodiazepines. That word does not appear in the 22 German warning. What the German warning says, as this 23 Court will recall, is that the doctor may want to give 24 a sedative. 25 THE COURT: May want to give what? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2252 1 MR. SEE: A sedative. Now, the reason, I 2 think, that Mr. Vickery withdrew the German warning 3 was the uncontroverted evidence from both of the 4 prescribing doctors, Dr. Roberts and Dr. Neal, that in 5 fact, when Dr. Roberts first prescribed Prozac, he 6 prescribed Inderal. For what? For anxiety. And he 7 prescribed also Desyrel. For what? To help 8 Mr. Forsyth sleep. And Dr. Neal's testimony is 9 identical. He continued those two drugs, one for 10 anxiety, one for sleep, for the same reason that 11 Dr. Roberts did. 12 So at that point, and that testimony is there, 13 and we're not going to have any different testimony 14 about that issue, the German warning becomes 15 irrelevant. We so moved, and I think Mr. Vickery saw 16 it and withdrew it. 17 What Dr. Matthews testified about had nothing 18 to do with that. All Dr. Matthews said was 19 Mr. Forsyth had taken the medication, Xanax, for 20 months. Mr. Forsyth had, in fact, obsessed and 21 worried that he was becoming addicted to Xanax and 22 wanted to get off of it. And two things could occur 23 after he gets off of it, number one, he no longer has 24 it as sort of a psychological crutch because he had 25 depended on it for so long; or two, perhaps his PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2253 1 symptoms of anxiety might return. That was 2 Dr. Matthews' testimony. It had nothing whatever to 3 do with should you give a sedative when you first 4 prescribe Prozac. Two totally unrelated subjects. 5 And on the topic that Mr. Vickery is now 6 talking about, the testimony is in the case, and I 7 don't think can possibly change, that the items the 8 German warning talks about were, in fact, done by the 9 doctors, so it wouldn't have made any difference. 10 THE COURT: I'm not going to allow you to go 11 into the German warning. 12 MR. VICKERY: Okay. The other issue, Your 13 Honor, that I wanted to raise with the Court 14 separately from the jury is the question of Dr. Reus' 15 prior testimonies on behalf of Lilly. I know the 16 Court has, you know, admonished us not to get into 17 other lawsuits involving Prozac, but it's very 18 important to me for the jury to understand how many 19 times Victor Reus has been hired by Lilly to testify 20 on this issue, including the times that he has 21 testified in criminal cases. I think that's something 22 that goes to his bias and to his credibility and 23 that's something I would like to bring out either with 24 appropriate cautions or instructions from the Court or 25 maybe for the witness. I wanted to apprise the Court PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2254 1 and Mr. See so the witness doesn't blurt something out 2 that he shouldn't. 3 THE COURT: Why can't you just ask him how many 4 times he's been engaged to testify for Lilly without 5 going into the fact that some of those were criminal 6 trials? 7 MR. VICKERY: I can do that. 8 THE COURT: Any problem with that, Mr. See? 9 MR. SEE: I think it probably is fair inquiry 10 to ask if the witness has been -- 11 THE COURT: I'll allow it. 12 MR. SEE: -- retained to testify before by 13 Lilly. 14 THE COURT: And I thank you for bringing these 15 up outside of the presence of the jury, Mr. Vickery. 16 MR. VICKERY: You're welcome, Your Honor. 17 THE COURT: We'll take a short break to allow 18 the jury to come in. 19 (Whereupon, a recess was taken at 9:20 a.m.) 20 (Whereupon, the following proceedings were had 21 in open court in the presence of the jury.) 22 THE CLERK: Civil No. 95-00185 ACK, Susan K. 23 Forsyth, et al. versus Eli Lilly and Company, et al. 24 MR. VICKERY: Good morning, Your Honor. Andy 25 Vickery, Roy Chang, and Karen Barth for the Forsyths. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2255 1 THE COURT: Good morning. 2 MR. SEE: Good morning, Your Honor. Andy See, 3 Michelle Mangrum, and Ed Burke for Eli Lilly and 4 Company. 5 THE COURT: Good morning. Good morning, ladies 6 and gentlemen of the jury. 7 Please proceed, Mr. Vickery. 8 MR. VICKERY: Thank you, Your Honor. 9 CROSS-EXAMINATION (Continued) 10 BY MR. VICKERY: 11 Q. Good morning, Dr. Reus. 12 A. Good morning. 13 Q. I wrote on the pad here what I think you were 14 saying yesterday, and I want to make sure I haven't 15 miswritten something. I saw you reading this before 16 you got up, right, on the stand this morning? 17 A. That's correct. 18 Q. What I wrote was -- first of all, you said that 19 the scientific literature with which you're familiar 20 is clear and there is no controversy; is that true, 21 sir? 22 A. That's correct, at this point. 23 Q. And what I believe I heard you say is it's 24 clear on three things. Number one, that akathisia is 25 a clear-cut phenomenon with both subjective and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2256 1 objective components as you demonstrated yesterday? 2 A. That's correct. 3 Q. And number two, that the SSRI drugs, like 4 Prozac and Paxil and Zoloft, do not cause akathisia? 5 A. That's not correct. 6 Q. Do they cause akathisia? 7 A. They can cause akathisia, yes. 8 Q. And so you think all three of them can cause 9 akathisia in some people? 10 A. All three what? 11 Q. All three of those drugs. 12 A. What three drugs are you referring to? 13 Q. Paxil, Zoloft and Prozac. 14 A. Yes, they can. 15 Q. All right. So let me clarify that. They do 16 cause akathisia? 17 A. They can cause akathisia. Not that they do 18 cause it. You have to evaluate each individual case. 19 Q. Is that one of these deals where we have to 20 have lots of clinical trials in the future or do you 21 believe that these drugs do cause akathisia in some 22 people? 23 A. I don't know if I can be more clearer than I 24 just have been. I said that SSRI drugs can cause 25 akathisia. Not necessarily do cause. Can cause. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2257 1 Q. Okay, sir. 2 A. It's a relatively rare side effect of SSRI 3 drugs. 4 Q. Okay, sir. And then the third one I wrote 5 down -- did I get this one right? -- is it your 6 opinion that from the scientific literature that 7 akathisia does not cause suicide or violence or do you 8 believe, in those rare cases where there is akathisia, 9 that it can cause it? 10 A. I don't believe that it causes suicide or 11 violence. I believe that what akathisia does is it 12 creates a state of severe anxiety which can exacerbate 13 pre-existing proclivities, tendencies, in an 14 individual to engage in either suicide or violence. 15 Q. So would you say then -- that was a mouthful of 16 words there. Are you saying that it can contribute to 17 suicide and violence in some people if they have 18 problems on which this is superimposed? 19 A. Akathisia is a state of extreme anxiety. 20 Anxiety in an individual who is predisposed to suicide 21 can increase the risk of suicide, that's correct. 22 Anxiety in the case of someone who is contemplating 23 violent actions or who is prone to violent actions can 24 lower the threshold for engaging in violent actions. 25 Q. Okay, sir. Let me have, if I may, your PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2258 1 specific opinion on the issue of whether Prozac causes 2 akathisia that causes or contributes in a material way 3 to violence or suicide. 4 A. Prozac can cause akathisia, doesn't necessarily 5 cause it, and as I said, it's a rare event. In a 6 study that the New Zealand government did surveying 7 over 5500 individuals who were on Prozac, they 8 identified only two individuals that experienced 9 akathisia. So at least in one large-scale 10 epidemiological study that's been published, it's a 11 very, very rare event. 12 Q. Okay. I want you to help me out on this, if 13 you can. Dr. Tiecher and Dr. Cole, at the conclusion 14 of their article, say that they think that the event 15 happens in 3-1/2 to 5 percent of people, don't they? 16 A. It's totally a mystery as to how they arrived 17 at that projection based on six case studies drawn 18 from their own practices. You cannot make 19 epidemiologic projections based on case reports in 20 your own practice. 21 Q. Okay. 22 A. It's a totally outrageous scientific thing to 23 do. 24 Q. I understand that's your opinion. 25 A. It's the opinion of any experienced PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2259 1 epidemiologist in the field. 2 Q. Well, what I want to know is, is that what they 3 said, that 3-1/2 to 5 percent of the people would have 4 this phenomenon? 5 A. That is what they said. 6 Q. Now, you're familiar with the meta-analysis 7 done by Dr. Beasley at Eli Lilly looking back at all 8 the patients in the clinical trials, are you not? 9 A. I recall that such a study was done, yes. 10 Q. Can you just explain for us what a 11 meta-analysis is? 12 A. It's an attempt to take a look at a number of 13 different studies that had been done and to try to 14 extract from all those studies some basic, sort of, 15 common conclusion, and it uses a variety of 16 statistical means to sort of take a look at the 17 numbers of subjects that were studied in each of those 18 cases, and then whatever the specific outcome you're 19 looking at, how big the outcome was, how big the 20 effects size was, and it tries to sort of, in some 21 way, compare apples and oranges and arrive at a common 22 answer from all of that common conclusion. 23 Q. Thank you. That was a very good explanation. 24 By comparing apples and oranges, there are sort of 25 built-in problems with that kind of analysis, aren't PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2260 1 there? 2 A. There could be. There are very good 3 meta-analyses and then there are meta-analyses that 4 are less good. 5 Q. In any event, you're familiar that in this 6 case, once the Teicher and Cole article came out, that 7 Lilly's Dr. Beasley did this meta-analysis and said, 8 let's look back at the clinical data and let's see if 9 we can find this 3-1/2 to 5 percent that Teicher talks 10 about. You know they did that, don't you? 11 A. I'm aware of that, yes. 12 Q. And you know they couldn't find them? 13 A. I believe that's the conclusion, yes. 14 Q. Now, I want to ask you this: What would you 15 describe as a psychiatric side effect of a drug? 16 A. A psychiatric side effect? 17 Q. Yes, sir. 18 A. I would say that a psychiatric side effect is a 19 side effect that predominantly has a behavioral 20 component to it, something that isn't easily 21 absorbable in a bodily part or a physical way. 22 Q. So something mental, in other words? 23 A. That's correct. 24 Q. Are you able to tell us, off the top of your 25 head, and if you're not, I'll give you the Lilly PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2261 1 package insert, but how many of the 4,000 people that 2 were involved in the clinical trials for Prozac 3 dropped out because of psychiatric side effects? 4 A. I don't know. 5 MR. VICKERY: May I have that Exhibit 2, 6 please? May I approach the witness, Your Honor? 7 THE COURT: You may. 8 Q (By Mr. Vickery) This is Plaintiffs' 9 Exhibit 2, and it's the label for Prozac that was in 10 effect at the time of the Forsyths' death. Okay. 11 That's what you were testifying about yesterday, is it 12 not, sir, that this label was adequate? 13 A. Yes, that's correct. 14 THE COURT: This is the same as 1041? 15 MR. VICKERY: Excuse me, Your Honor? 16 MR. SEE: It is, Your Honor. 17 Q (By Mr. Vickery) Now, would you look in the 18 table there and tell us, of the 4,000 people who were 19 involved in the clinical trials, what percentage 20 dropped out because of psychiatric side effects? 21 A. "Fifteen percent of the approximately 4,000 22 patients who received Prozac discontinued treatment 23 due to an adverse event." This is right in the 24 ballpark with what happens with any clinical trial 25 with an antidepressant. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2262 1 Q. I know 15 percent dropped out because of some 2 adverse event. Now, some of those were rashes, some 3 of them were nausea and stuff like that, right? 4 A. I would suppose so. Here it is, "The most 5 events included -- discontinuation included 6 psychiatric, 5.3 percent." And it goes on to say, 7 "Primarily nervousness, anxiety, and insomnia." 8 Q. Nervousness and anxiety are the kinds of 9 psychiatric side effects that they had? 10 A. And insomnia. 11 Q. Now, we've already heard extensive testimony 12 from Dr. Healy about the fact that a patient reporting 13 a side effect that a doctor might call akathisia, 14 might use a word like nervousness or anxiety. Do you 15 agree with that? 16 A. The diagnosis of akathisia requires both a 17 subjective and an objective component, so the doctor 18 diagnosing akathisia would get the complaint of 19 nervousness, but in addition, would have to see a 20 motor abnormality to make the diagnosis. 21 Q. But if we're just talking about people that 22 dropped out from the 4,000 that were studied and 23 5.3 percent is what, 212 people? 24 A. That's about right. 25 Q. So if 212 people dropped out because they PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2263 1 reported they were nervous or had anxiety -- 2 A. Or couldn't sleep. 3 Q. -- or couldn't sleep, that very well could be 4 the kind of subjective inner restlessness that one 5 calls akathisia, couldn't it? 6 A. No. It's not sufficient. I want to emphasize 7 that because we know anxiety is a very common 8 complaint. We know insomnia is a very common 9 complaint in people who are depressed and even in 10 conjunction with medications that were given. That is 11 not the same as akathisia. Akathisia requires both 12 the subjective experience and the motor abnormality. 13 Q. Okay. 14 A. You have to have both. 15 Q. I know you've said that and, believe me, that's 16 right where I want to go right now. One of the 17 journals that is recognized by folks in your field 18 and, indeed, in which you have published, is the 19 Journal of Psychopharmacology, isn't it? 20 A. I don't believe I've ever published in the 21 Journal of Psychopharmacology. 22 Q. Well, that is a recognized journal in your 23 field, isn't it, a peer-reviewed journal? 24 A. Are you sure about the title? 25 Q. Yes, sir. Journal of Psychopharmacology. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2264 1 A. It's not Journal of Clinical Psychopharmacology 2 or Journal of Experimental Psychopharmacology or just 3 plain Psychopharmacology? 4 Q. It may have previously been called one of those 5 others, but now it is called the Journal of 6 Psychopharmacology. 7 A. Okay. It's not one of the main journals. I'm 8 not familiar. 9 Q. But it's a peer-reviewed journal in that field 10 you would recognize as being a valid authority, 11 wouldn't you? 12 MR. SEE: Objection, asked and answered. No 13 foundation. 14 THE COURT: He said he's never heard of it. 15 Q (By Mr. Vickery) Well, have you ever heard of 16 a company in New York called Pfizer? 17 A. Yes, I have. 18 Q. And do they manufacture an SSRI drug called 19 Zoloft? 20 A. Yes, they do. 21 Q. And do they have good scientific people that 22 work for them? 23 A. I'm sure they have good people and they have 24 people like any organization who maybe aren't good. I 25 have no idea about characterizing their work first. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2265 1 Q. Well, if an article was published by a Pfizer 2 scientist on this very issue, you would give that some 3 weight, wouldn't you? 4 MR. SEE: I object. There's no foundation for 5 the witness to answer the question. What article? 6 MR. VICKERY: Well, I'm about to show him, Your 7 Honor. I just need to know if he would -- 8 THE WITNESS: I don't judge articles on what 9 organization they come from. I judge articles on the 10 soundness of their scientific methodology and the 11 findings that emerge. 12 THE COURT: I think he's answered the question, 13 so I will overrule the objection. 14 MR. VICKERY: Thank you, Your Honor. 15 Q. I'd like to show you -- 16 MR. VICKERY: If I may approach, Your Honor? 17 THE COURT: You may. 18 Q (By Mr. Vickery) -- an article published last 19 June, June of '98 in the Journal of Psychopharmacology 20 by a Pfizer scientist by the name of Roger M. Lane. 21 Do you know Dr. Lane? 22 A. No, I do not. 23 Q. Okay. His article is entitled, "SSRI-induced 24 extrapyramidal side effects and akathisia, 25 implications for treatment." Have you had a chance to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2266 1 look at Dr. Lane's article before? 2 A. No, I have not seen this article before. 3 Q. Let's look at it together then. You see the 4 title here, "SSRI-induced extrapyramidal side effects 5 and akathisia." 6 MR. SEE: Your Honor, may I object. There's no 7 foundation for questioning about the article. The 8 journal has not been identified, the foundation has 9 not been laid. 10 THE COURT: Sustained. 11 Q (By Mr. Vickery) Dr. Reus, would you just 12 take a minute -- take that off. Would you just take a 13 minute and look at that article, take as long as you 14 want, it's kind of a lengthy article, and tell me 15 whether or not you accept that article from a Pfizer 16 scientist, published last year in a peer-reviewed 17 journal, as an authoritative work or is that something 18 that you're just going to discard? 19 A. Again, this is 24 pages. If you want me to sit 20 here and read it to reach that conclusion, I can do 21 so, but it's going to take, judging from the type 22 size, about an hour and a half to do so. 23 Q. I don't want you to read through the whole 24 thing. I just want you to look at the journal, see if 25 you can assure yourself, from the cover of the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2267 1 journal, the editorial board that's shown on the 2 document there and the author, the fact that it's from 3 somebody in Pfizer saying something bad about their 4 own drugs -- 5 A. I don't know, first of all, what the article 6 says, so I can't agree with you that it says something 7 bad. Secondly, again, I'm on record as saying I don't 8 judge articles on the basis -- I don't know Mr. Lane. 9 I don't know anything about his background. I don't 10 know anything that he said. And before I can agree 11 with you about any conclusions that are drawn, I'd 12 have to read the article. I can't give you an 13 evaluation of an article without having read it. 14 Q. Well, what I want to do, sir, since you've told 15 us, in your direct testimony, you're familiar with all 16 the scientific literature. 17 A. I'm familiar with the prevailing views in the 18 scientific literature. If you're meaning to suggest 19 that I implied that I have read every article in the 20 scientific literature, I am perfectly happy to say I 21 haven't. 22 Q. Well, let me just ask you this: Is it apparent 23 to you from the title that this article is about SSRI 24 drugs and akathisia? 25 MR. SEE: Your Honor, again, I object. There's PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2268 1 no foundation to question on the article. 2 MR. VICKERY: Your Honor -- 3 THE COURT: I'll sustain the objection. 4 MR. VICKERY: Your Honor, I can represent to 5 the Court that other experts pursuant to 803.18 will 6 identify this as a peer-reviewed journal and -- 7 THE COURT: This gentleman has not read the 8 article and has never heard of the journal. He's 9 never heard of the author. 10 MR. VICKERY: Well, Your Honor -- 11 THE COURT: He doesn't know whether it's peer 12 reviewed. 13 MR. VICKERY: Mr. See cross-examined Dr. Healy 14 on articles he had never read. They came from 15 peer-reviewed journals. He was given that latitude 16 under 803.18 to cross-examine my expert. I have this 17 article that's recent, that's published by somebody 18 who really would be making statements against their 19 own interest. 20 THE COURT: He hasn't read the article. 21 MR. VICKERY: I understand that and that's part 22 of my point. That's my criticism. 23 THE COURT: All right. You've made that point. 24 Q (By Mr. Vickery) Okay. Well, let's turn to 25 something else then. You prepared and signed a sworn PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2269 1 declaration in this case, correct? 2 A. That's correct. 3 Q. And in that declaration you were very critical 4 of the reliance by Dr. Healy on what you called case 5 reports? 6 A. That's correct. 7 Q. Now, did you prepare that declaration 8 specifically for this case? 9 A. Yes, I did. 10 Q. Did you write it yourself? 11 A. Yes, I did. 12 Q. Okay. 13 MR. VICKERY: If I may approach, Your Honor? I 14 have his declaration for him. 15 THE COURT: You may. 16 Q (By Mr. Vickery) I'm talking about your 17 declaration, not your report. 18 A. Well, I thought you were talking about my 19 report. 20 Q. No, sir. I'm talking about the declaration 21 that you signed here. It's a 10-page document signed 22 by you on July the 16th, 1997? 23 A. Yeah, this is -- I didn't specifically prepare 24 this. I reviewed it and signed it. 25 Q. It's a 24-paragraph document and it says, "I PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2270 1 declare under penalties of perjury that the foregoing 2 is true and correct." 3 A. That's correct. 4 Q. Now, if you didn't prepare this 24-paragraph 5 document, who did? 6 A. My understanding is that the law offices of 7 Mr. See did. 8 Q. And is it your practice to sign things under 9 penalties of perjury that were prepared by Mr. See? 10 A. I only sign something that I agree with. I 11 review it, I look at it, and I change it and edit it 12 according to what I think is accurate and true. So 13 I -- 14 Q. Did you change or edit this one? 15 A. I don't recall as to whether I did or not. 16 Q. Would it surprise you to know, Dr. Reus, that 17 most of the paragraphs or a number of the paragraphs 18 in your sworn declaration are identical, verbatim to 19 sworn declarations by other witnesses in other cases 20 involving Mr. See? 21 A. Well, to the extent that it reflects the common 22 truth in the land and an agreed-upon understanding 23 about people in the field, and to the extent that 24 Mr. See is able to accurately reflect that 25 understanding, I don't see that as surprising. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2271 1 Q. Okay. So it's all right with you if Mr. See 2 has this scientific information in his word processor 3 and if he just prints it and gives it to another 4 expert in another case, and to you in this one, and 5 you sign it under penalties of perjury? 6 MR. SEE: Objection, asked and answered, and 7 the form of the question, argumentative. 8 THE COURT: I'll sustain the objection. 9 Q (By Mr. Vickery) I want to talk to you about 10 what you were sharing with us yesterday about the 11 statistical significance. If one is looking for a 12 rare phenomenon, and specifically the phenomenon that 13 you told us this morning can rarely be caused by SSRI 14 drugs, that is akathisia, how many people do you have 15 to have in a study in order to have something that's 16 reliable with statistical significance? 17 A. It depends on the number of people who were 18 studied and what's called the effect size, how 19 frequently something occurs. 20 Q. Well, that's what I'm talking about. I'm 21 talking about something -- let's say Teicher and Cole 22 were right and it happens with 3-1/2 percent to 23 5 percent of the population. How many thousands and 24 thousands of people would you have to have in a study 25 to reach a statistically significant result? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2272 1 A. The answer to that is determined by what's 2 called power analysis, which is a statistical way that 3 looks at how frequently something occurs and then 4 looks at how frequently it would occur, for example, 5 in a placebo condition without being associated with 6 the meds. So the difference between those two facts 7 or current rates is what's called the effect size, and 8 if it's a big difference, then you need fewer people 9 in order to arrive at a statistically significant 10 finding, and if it's a small difference, then you need 11 a great number of people to be able to demonstrate a 12 difference. 13 Q. Can you ballpark it for us? If we're looking 14 for something that happens in 3-1/2 percent of the 15 people, are we talking about hundreds of thousands of 16 patients? 17 A. I can't ballpark it for you because I'm not 18 familiar offhand with -- first of all, this is an 19 assumption that I don't agree with in terms of the 20 prevalence rate, but you'd have to know what the 21 prevalence rate is in, again, a population that -- I 22 mean, you'd have to define the population, is it in 23 depressed patients, depressed patients of what age, 24 what gender? You know, you just have to look at all 25 those factors because the rates in which something PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2273 1 occurs can be affected by all of those factors. 2 Q. There's another phenomenon called confounding, 3 is there not? 4 A. Yes, that's just what I was talking about, 5 confounding variables. 6 Q. And just to use simple jargon, those are things 7 that make it difficult to understand the literature? 8 A. Yes, that's correct. 9 Q. All right. I want to use a hypothetical with 10 you. Prozac probably helps some people in terms of 11 reducing their suicidality, doesn't it? 12 A. I would say it helps a great many people in 13 decreasing suicidality. 14 Q. Okay. So if there were, let's say, 100 people 15 and they were all depressed people, and we know 16 statistically that about 15 percent of people who are 17 depressed will commit suicide sometime over the course 18 of their lives, right? 19 A. Of people who have been inpatients, who are 20 depressed, that's correct. 21 Q. How about for people who are outpatients, 22 what's the rate? 23 A. It's probably lower. 24 Q. Much lower, isn't it? 25 A. Not -- it's subject to doubt. It's not clear. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2274 1 There are differences in opinion as to how much lower 2 it is. 3 Q. Can we use ten just for our hypothetical? 4 A. Sure. 5 Q. All right. So let's say there are 100 people 6 that are depressed, and 10 of them are thinking about 7 killing themselves, okay? 8 A. We're talking about outpatients now or people 9 who have an inpatient hospitalization? 10 Q. We're talking about outpatients for the 11 hypothetical, all right? And let's say, all these 12 folks -- there just happens to be ten people sitting 13 in the courtroom behind the bar. So let's say all ten 14 of those people were depressed and they all were 15 thinking about killing themselves. Are you with me so 16 far? 17 A. I'm not sure, but please go on. 18 Q. Let's say I'm depressed, but I'm not thinking 19 about killing myself, okay? But we're all given 20 Prozac. Now, if we look at it from a statistical 21 standpoint, it's possible that the Prozac could help 22 all ten of those people, but make me become akathisic 23 and suicidal; isn't that true, sir? 24 A. Are you saying you already were suicidal? 25 Q. No, sir. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2275 1 A. No. I think I'm on record of saying that I do 2 not believe that Prozac -- or that akathisia causes 3 suicide in an individual who's not already expressed 4 suicidal thoughts. So I do not agree it could make 5 you suicidal. 6 Q. But if the jury were to believe that, from 7 other testimony, that it made me suicidal, for my 8 hypothetical, just assume that with me, okay, that I 9 become suicidal, wasn't before, but become suicidal? 10 A. Well, I can't agree with you that Prozac causes 11 you to become suicidal. 12 Q. I'm not asking you to. I'm just asking you to 13 assume for the purposes of my question -- it's a 14 hypothetical question. 15 A. I understand. 16 Q. -- that I become suicidal and I wasn't before, 17 and I'm asking you to assume with me, even though I 18 know it's not your opinion, that Prozac caused me to 19 become suicidal. This goes to statistics, okay? What 20 I'm trying to suggest to you, Doctor, is that if we 21 looked at this statistically, globally, of the hundred 22 people, ten would have been helped, one would have 23 been hurt, and I'm just statistically insignificant in 24 that hypothetical, aren't I? 25 MR. SEE: Objection, incomplete hypothetical PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2276 1 and the question is argumentative without foundation. 2 THE COURT: Well, I'll allow Mr. Vickery to 3 pursue that. 4 MR. VICKERY: Thank you, Your Honor. 5 THE COURT: You'll have to clear it up, though, 6 Mr. Vickery. 7 THE WITNESS: Well, I think I'm losing your 8 point. I don't consider any suicide as a 9 statistically insignificant event. It's a serious 10 event and, again, has to be looked at in detail if it 11 occurs. If it occurs in a study, for example, of 12 eleven individuals and one person commits suicide, 13 that is a very serious and significant event that 14 would attract a lot of attention. 15 Q (By Mr. Vickery) I didn't mean to suggest 16 that -- 17 A. It was your specific hypothetical that I was 18 responding to. 19 Q. I'm just talking about looking at the numbers. 20 I'm not talking about how you would feel about my wife 21 or my family if I killed myself. I'm talking about if 22 you looked at the numbers and the numbers show that 23 ten got better and one got worse, doesn't the one that 24 got worse get hidden, sort of swept along with the ten 25 that got better? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2277 1 A. I don't know where that conclusion comes from. 2 Q. Well, it comes from the Ham-D. Do you know 3 what the Ham-D Item 3 is? 4 A. Yes, I do. 5 Q. And the Ham-D Item 3, if that's what we used to 6 measure suicidality, then these ten folks would have 7 had a three or four and I would have had a zero on 8 that scale, and then at the end, they would have a 9 zero or a one, but I'd have a four, and if one is 10 doing a meta-analysis, if you're just crunching the 11 numbers and if you're just looking at that one little 12 scale, don't I get washed up with the ones that were 13 helped? 14 MR. SEE: I object to the form of the question. 15 It's an incomplete hypothetical. 16 THE COURT: I'll allow it if the witness can 17 make sense of it. 18 THE WITNESS: Well, I think I am having trouble 19 making sense of it. All I can say is that going back 20 to why we use statistical rules to evaluate data, we 21 know that certain events occur by chance alone or 22 occur as a result of confounding variables, that's 23 variables other than the one we're looking at. And in 24 the same sense of tossing a coin and having a coin 25 come up heads five times in a row or ten times in a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2278 1 row, we know that occurs by chance, and so that's why, 2 going back to what I mentioned yesterday about the 3 .05 standard, we set up rules for how we look at 4 scenarios that you've just described. 5 Q (By Mr. Vickery) And that's the reason I 6 described that because -- when you analyze it using 7 those rules, you miss some cases where there's been 8 genuine causation, isn't that true? They get swept up 9 because of the -- 10 A. No, I don't think you've established causation. 11 I think that if you're saying that, in a rare event, 12 there are other approaches to trying to take a look at 13 causation in a rare event, I would agree with that, 14 but you have to establish causation. 15 Q. How would you establish causation in a rare 16 event? 17 A. Well, again, one of the best ways to do it, as 18 I said, with rare events, is to do large-scale 19 epidemiologic studies where you're looking at 20 population samples that are very large. 21 Q. One of the problems with those, though, is that 22 you're always doing what's called a cohort, looking 23 back at what's been done, aren't you? 24 A. You could do a prospective epidemiologic study. 25 Q. How much would it cost to do a prospective PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2279 1 epidemiological study on this issue given the rarity 2 of the problem? 3 A. I have no way to answer that. I mean, it's 4 being done. Similar epidemiological studies are being 5 done in other areas of medicines, in cancer and heart 6 disease. It's just that the National Institute of 7 Mental Health has lagged so far in setting up 8 large-scale national databases in mental health and 9 it's because mental health has been historically 10 underfunded. 11 Q. Wouldn't it take -- 12 A. It's an expensive enterprise. 13 Q. To do one looking forward, in other words, to 14 set the study design now to look for this phenomenon 15 as opposed to looking back at what's been done and 16 saying, can we find it, but to try to look at it in 17 the future, it would take $10 million, wouldn't it? 18 A. I don't know where that figure comes from. 19 Q. It comes from Dr. Healy. Do you agree with it? 20 A. Again, I can't agree with it because I don't 21 know what it's based on. 22 Q. Okay. Well, can you tell me, have any 23 prospective studies ever been done on this issue? 24 A. On what issue? 25 Q. On Prozac causing akathisia which causes PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2280 1 suicide. 2 A. Well, I'm not aware of large-scale prospective 3 studies. There have been prospective studies in 4 individual clinics that have begun to take a look at 5 this, yes. 6 Q. Involving 600 people here and there? 7 A. Yeah, about that size. 8 Q. And is that a large enough study population to 9 come to any statistically significant conclusions if 10 we're looking for a rare phenomenon? 11 A. Well, if you believe Teicher and Cole, it 12 certainly should be. If you believe that it occurs 13 5 percent of the time, precipitated 5 percent of the 14 time, it should be certainly evident of that. 15 Q. Is that really true, if you're looking for a 16 5 percent occurrence, the power curve only requires 17 600 people to tell us if that phenomenon has occurred? 18 A. Well, if you will tell me how often that occurs 19 by chance alone. Will you tell me that? 20 Q. I'm not sure I know. 21 A. Okay. Well, how does 5 percent come in then? 22 Q. That's just what Teicher and Cole suggested. 23 A. And where does that come from? 24 Q. From their 50, 60 years of accumulated 25 experience, so it comes out of their clinical PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2281 1 experience. 2 A. Their clinical experience. 3 Q. And you've read their article as much as I 4 have. 5 A. And these are the questions I have about it and 6 I was hopeful you could enlighten me about where it 7 came from. 8 Q. Well, as I read it, it came from the 9 accumulated two very senior men, one of whom was hired 10 by Eli Lilly to test this drug. 11 MR. SEE: Your Honor, I object to counsel 12 testifying. I move that his question be stricken. 13 THE COURT: I'll sustain the objection and 14 strike it, and you may ask the question of this 15 witness. 16 Q (By Mr. Vickery) Okay. Now, I just lost my 17 train of thought. Bear with me. 18 Let's look at the Rothschild. You're familiar 19 with that paper, aren't you. 20 A. Which Rothschild paper? 21 Q. The rechallenge with three patients. 22 A. Yes, I am. 23 Q. Now, do you agree that dechallenge and 24 rechallenge are valid ways to prove a drug effect? 25 A. If you have a placebo control. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2282 1 Q. Why do you have to have a placebo control if 2 you have someone -- Dr. Healy used a very graphic 3 example for us. If you have something that's clear, 4 that happened, is dose related, it happens right after 5 the event, why do you really need a placebo control? 6 A. Well, if the event that you're looking for is 7 an extremely unpleasant one like akathisia is -- this 8 is something that was discovered by Ivan Pavlov and he 9 got the Nobel Peace Prize for it. It is called 10 classical condition, and what it means is that if you 11 have a very specific unpleasant experience, you tend 12 to associate it with whatever has been going on at 13 that time, and so if you rechallenge someone with 14 maybe not even the original stimulant, but something 15 that was around at that time, you can get the exact 16 same response. 17 Q. Can't the control be supplied in some 18 instances, Dr. Reus, by just our common experience? 19 A. This gets to the issue of bias, which I tried 20 to suggest to you yesterday. It is a major 21 confounding variable in scientific study which is why 22 we have placebo controls. 23 Q. Let me -- Dr. Healy picked on me, but he talked 24 about giving me alcohol that would make me drunk, 25 okay. Now, a placebo control, I guess, would be this PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2283 1 glass of water. 2 A. No. 3 Q. What would it be? 4 A. Because you could discern the difference 5 between water and alcohol. 6 Q. But if the people that are measuring it is not 7 me, but is someone else -- 8 A. What you try to do in alcohol studies, which 9 they actually do do placebo controls, you imbed the 10 alcohol in a very strong tasting substance that covers 11 up the flavor of the alcohol, so you have a true 12 placebo and one has the alcohol in it. 13 Q. Would we really have to have -- in the example 14 he used with me, I had a bunch of gin and everybody in 15 the courtroom saw that I became intoxicated shortly 16 after having it and shortly after imbibing in quantity 17 of it. That would give a dose response relationship. 18 Do we really have to have a placebo to conclude that 19 this guy got drunk on gin? 20 A. Again, can you describe to me what the 21 circumstance -- what the scientific study is? 22 Q. It's a challenge, dechallenge, rechallenge. 23 A. But, again, you're given gin and then what's 24 happening? 25 Q. I'm getting drunk. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2284 1 A. And then you wait awhile and you get gin? 2 Q. I wait awhile and then I got sober. That's the 3 dechallenge. And I get gin or bourbon that's got 4 alcohol in it. 5 A. Well, it's important, if you're going to 6 rechallenge, to use the exact same substance. If you 7 don't use the exact same substance, the reaction that 8 occurs might not be due to some other change that 9 occurs, may be due to something else that's in there, 10 not the alcohol. It may be due to something 11 associated with the gin or the bourbon. 12 Q. So even though alcohol is common to both, that 13 doesn't suffice for you? 14 A. No, because you've introduced an additional set 15 of variables. 16 Q. Okay. Let's look at what Dr. Rothschild and 17 his colleagues did. "Re-exposure to fluoxetine -- 18 whenever we see that word, we just stay Prozac here, 19 okay. "Re-exposure to Prozac after serious suicide 20 attempts by three patients, the role of akathisia," by 21 Anthony Rothschild and Carol Glod. Do you know 22 Dr. Rothschild? 23 A. Yes, I do. 24 Q. Is he a reputable Harvard physician? 25 A. He's not at Harvard. He's at the University of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2285 1 Massachusetts. 2 Q. Okay. "Considerable controversy exists 3 regarding the relationship between Prozac and the 4 emergence of suicidal ideation. Three cases were 5 presented of patients who were re-exposed to Prozac 6 after having previously made a serious suicide attempt 7 during Prozac treatment. All three patients developed 8 severe akathisia during retreatment with Prozac and 9 stated that the development of the akathisia made them 10 feel suicidal and that it had precipitated their prior 11 suicide attempts. The akathisia and suicidal thinking 12 abated upon the discontinuation of the Prozac." 13 Abated means stopped, didn't it? 14 A. Sorry? 15 Q. Does abated mean it went away? 16 A. Means it decreased. 17 Q. Okay. "Or the addition of propanolol." What's 18 propanolol? 19 A. It is a beta blocker, Inderal. 20 Q. Okay. The -- 21 A. It's actually the treatment of choice for 22 akathisia. 23 Q. All right. "The emergence of suicidal ideation 24 during treatment with Prozac may be secondary to the 25 development of akathisia." Now, that's what they say PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2286 1 there is what you disagree with, you don't believe it? 2 A. I'm sorry, I unfortunately can't see that far 3 with my eyes. 4 Q. That's why I was trying to say it slowly and 5 loudly. "The emergence of suicidal ideation during 6 treatment with Prozac may be secondary to the 7 development of akathisia." Do you agree with what 8 they say about that or disagreement? 9 A. Again, I'd have to know more about pre-existing 10 suicidal thoughts or actions. My point was that it 11 doesn't occur denovo. 12 Q. Okay. "Gradual increments of Prozac dose and 13 the prompt direct admission and treatment of akathisia 14 may reduce further the rare occurrence of suicidal 15 ideation during Prozac treatment." Now, didn't they 16 do, with these three patients, exactly what Lilly had 17 planned to do, but did not do with respect to 200 18 patients, to study this issue? 19 A. I have no idea what Lilly planned to do or did 20 not do. 21 Q. Has Mr. See not shared with you any of the 22 Lilly internal documents on this issue? 23 A. I haven't looked at internal documents, no. 24 Q. So you've never seen the protocol drafted by 25 Dr. Beasley? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2287 1 A. What protocol are you referring to? 2 Q. I'm talking about the rechallenge protocol that 3 he drafted in 1991. 4 A. I haven't seen that, no. 5 Q. Okay. Do you know who Sir Austin Bradford Hill 6 is? 7 A. No, I do not. 8 Q. Do you know who devised the idea of controlled 9 clinical trials? 10 A. Devised the idea of controlled clinical trials? 11 Q. Isn't it an Italian guy name Lasagna? 12 A. Louis Lasagna? 13 Q. Yes. 14 A. Well, I think that it's sort of like -- that's 15 a little bit like Al Gore inventing the Internet, I 16 think. 17 Q. Okay. 18 A. I'd say Charles Sharington was probably the 19 person who... 20 Q. Dr. Reus, how many times have you been employed 21 either by Eli Lilly or by Shook, Hardy, and Bacon to 22 testify? 23 A. Testify in general or -- 24 Q. Well, testify with regard to Prozac. 25 A. My recollection is that -- I would say, to the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2288 1 best of my ability to pull it out, it's about eight 2 times for cases. 3 Q. Okay. Now, yesterday we were talking about the 4 fees. You charge $2200 a day, correct, sir? 5 A. For testimony, yes, that's correct. 6 Q. And I guess you charge more for testimony than 7 for non-testifying work? 8 A. No. Actually, it ends up being less. 9 Q. Less, okay. And you said yesterday, all the 10 money goes to the University of California? 11 A. It has for the last two years, yes. 12 Q. Does the University of California have what's 13 commonly called a soft money compensation arrangement 14 with professors such as yourself? 15 A. What do you mean soft money? 16 Q. I mean that your salary, how much of it that 17 comes back to you once it goes into the university is 18 dependent upon how much money from either research or 19 testifying or other things that you bring into the 20 university. 21 A. There are individual arrangements that can be 22 made, yes. 23 Q. And do you have such individual arrangements? 24 A. It varies by year to year. It depends on how 25 much -- if you have a surplus at the end of the year, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2289 1 then you can request to have it given back to you or 2 you can leave it in and apply it to time when you 3 don't have grants that come through and things like 4 that. 5 Q. I'm just trying to determine on whether or not 6 you have an indirect financial interest in the fees 7 that you generate from testifying on behalf of Lilly 8 in this and other cases. 9 A. Well, you can request amounts of money as sort 10 of -- it is taxed by the dean and by the chairman and 11 then you can request at the end of the year some 12 repayment from that. The department withholds, I 13 don't know exactly what the formula is, but something 14 like one-and-a-half times your salary in a reserve, so 15 it has to be -- whatever you have inside has to be 16 beyond that. 17 Q. Okay, sir. Now, yesterday you gave what I 18 thought was a very excellent explanation of how the 19 clinical trials are set up to work. Are those 20 designed to test efficacy mainly? 21 A. Yes. Usually. 22 Q. So that we understand, a scientist -- 23 A. Let me just clarify that. There are really -- 24 before you get to efficacy, there are trials that look 25 at toxicity. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2290 1 Q. Right. 2 A. And so those are also controlled clinical 3 trials. 4 Q. Dr. Tollefson explained that for us last week, 5 but once we get into the phase one, phase two trials, 6 what we're doing is looking for, does this drug work? 7 In case of depression studies, does it relieve 8 depression, correct, sir? 9 A. That's correct. 10 Q. Now, when you do that, how many of the 11 different trials that are done have to work for the 12 company in order for the FDA to approve the drug for 13 them? 14 A. I don't think there's any specific formula for 15 that. 16 Q. Are you aware that with respect to Prozac, 17 there were, oh, lots of studies done and only a 18 handful of them showed that it actually worked on 19 depression? 20 MR. SEE: Your Honor, I'd object. It's outside 21 the scope of this witness' direct examination. 22 Relevance. 23 MR. VICKERY: I'm responding to the direct 24 examination where he was asked to explain all about 25 clinical trials, Your Honor. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2291 1 THE COURT: I'll allow it. 2 THE WITNESS: Yeah, that's unfortunately one of 3 the true facts about treatment of depression, and 4 actually, treatment of psychiatric conditions in 5 general is the very large placebo response rate, and 6 it's been true for every antidepressant drug 7 specifically that's been brought to market. There's a 8 large number of trials that show no difference even 9 though we know the drugs are effective. So that's one 10 of the reasons why you do have placebo controls. 11 Q (By Mr. Vickery) In other words -- 12 A. Because if you didn't have a placebo control, 13 you could bring a drug to market that really didn't 14 have any effect, but was brought to market anyway 15 because it was no different from a drug that was 16 currently on the market. 17 Q. So if it worked, say, 2 times out of 27, and my 18 recollection is that's the order of magnitude we're 19 talking about here. 20 MR. SEE: Your Honor, I object to Mr. Vickery's 21 testifying and I ask that it be stricken. 22 THE COURT: Sustained. 23 Q (By Mr. Vickery) Let me ask you, are you 24 aware of the order of magnitude of studies that were 25 done for Prozac before it was approved by the FDA for PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2292 1 depression? 2 A. All I can tell you is that the FDA has very set 3 and standard guidelines for how it evaluates whether a 4 drug is effective or not, and I don't know how many 5 studies were done by any of the different drugs. 6 Q. What would happen if you did a meta-analysis on 7 all of those, if you lumped them all together and say, 8 does this drug really work? 9 A. I have no idea. It depends on the number of 10 subjects studied. You could have a couple large-scale 11 studies that show a big-effect size and you could have 12 others that just missed. So you can't tell just by 13 the number of studies. 14 Q. Are you familiar with any instance in which Eli 15 Lilly has dispatched an executive on a mission to keep 16 people from publishing scientific literature? 17 MR. SEE: Your Honor, I object. It's contrary 18 to the Court's prior rulings. It's beyond the scope. 19 THE COURT: I'll sustain the objection. 20 MR. VICKERY: May I be heard? 21 THE COURT: Side bar. 22 (Whereupon, the following proceedings were had 23 at side bar out of the hearing of the jury.) 24 MR. VICKERY: Your Honor, the reason I asked to 25 be heard on it is that what this man has testified to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2293 1 is that he's familiar with all this scientific 2 literature. He's come in and suggested that he's 3 reviewed all of the scientific literature and there's 4 no problem on there -- 5 THE COURT: He specifically qualified his 6 testimony that he has not read all the scientific 7 literature. 8 MR. VICKERY: Well, he has certainly said -- I 9 forget the exact word he used, the consensus or the 10 trend, he used a word like that. I can't recall 11 exactly the word he used, but the impression he 12 created is the weight of the scientific literature is 13 that there is no problem here between Prozac and 14 suicidality. 15 The fact that Eli Lilly sent someone on a 16 mission, which was accomplished by someone not 17 publishing scientific literature, is very important 18 impeachment. 19 THE COURT: This has been asked to 20 Dr. Tollefson. 21 MR. VICKERY: Yes, it was. 22 THE COURT: I thought he explained that rather 23 effectively. 24 MR. VICKERY: Well, what I hoped to do is he's 25 going to say -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2294 1 MR. SEE: Keep your voice down. 2 MR. VICKERY: He's going to say one or two 3 things, either he has seen that memo or he hasn't, and 4 if he hasn't -- 5 THE COURT: This is an internal memo. 6 MR. VICKERY: Okay. Your Honor, that's one of 7 the problems I have, I guess, in that if my 8 cross-examination of the witness is limited to what he 9 has seen, then I can't very well point out the impact 10 of the things that he hasn't seen. 11 THE COURT: He pointed out that he hasn't seen 12 any internal memos so he would not know anything about 13 this. 14 MR. VICKERY: I understand, but don't you think 15 it is a fair question for me to say to him that if the 16 evidence is that Lilly is suppressing literature -- 17 THE COURT: He testified that they're not. 18 MR. VICKERY: Well -- 19 THE COURT: You've already gone into that 20 thoroughly with Dr. Tollefson. 21 MR. VICKERY: While we're over here, I would 22 like to ask you to reconsider the cross-examination on 23 the Lane article. I mean, this is a very important 24 article. 25 THE COURT: He says he doesn't know it is a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2295 1 peer-reviewed article. 2 MR. VICKERY: It is from a publication that is 3 listed as that. I can show the Court the deal. 4 THE COURT: You can ask him whether it is peer 5 reviewed. 6 MR. VICKERY: Judge, this man has been coached 7 to say no. He has been told, all you have to do is 8 say no, you don't know, and you don't have to be 9 cross-examined on these documents. The problem -- 10 MR. SEE: I resent that statement and it is not 11 true. 12 MR. VICKERY: Well, I find it hard to believe, 13 that how readily he's talked about all these various 14 other publications, and here's the one that I've got 15 that the reliability is clear because of statements 16 against the interest -- it's against Pfizer's interest 17 to publish what they did, but what they did is knock 18 this man out of the park in akathisia and it was 19 published six months ago by an SSRI manufacturer. And 20 it is very important cross-examination for me. I want 21 the Court to reconsider that relief. 22 THE COURT: You better establish the -- 23 MR. VICKERY: I think the Court can take 24 judicial notice that it's a peer-reviewed journal. 25 It's been -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2296 1 THE COURT: I don't know that. I don't know if 2 it's peer reviewed. 3 MR. VICKERY: It lists the editorial board. It 4 shows right at the front of the article. I mean -- 5 THE COURT: You can ask him. 6 MR. VICKERY: But he's going to deny it because 7 he knows what's coming. 8 THE COURT: He said he's never read it. 9 MR. VICKERY: Do you think, when I pull 10 something like that out, that this guy isn't cagey 11 enough since he's testified eight times for Lilly? 12 MR. SEE: Wait a minute. 13 MR. VICKERY: Excuse me. He is cagy enough to 14 know, all I've got to do is say, I don't recognize it, 15 and the judge is not going to let Mr. Vickery 16 cross-examine on it. This knocks him out of the park 17 on akathisia. It is six months ago, and it says 18 exactly opposite of what Mr. See has assured the Court 19 in this situation on akathisia and what this witness 20 has testified to. 21 THE COURT: What does it say? 22 MR. VICKERY: It says it is subjective 23 sometimes. It is objective, but frequently it goes 24 unnoticed because of the subjective. 25 MR. SEE: Dr. Healy testified about that -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2297 1 MR. VICKERY: I know. 2 MR. SEE: -- for days. 3 MR. VICKERY: Yes, he did, but what you see -- 4 what they're going to do is make him look like some 5 kind of voice crying in the wilderness. 6 THE COURT: Did Dr. Healy say this was a 7 peer-reviewed article? 8 MR. VICKERY: This particular article he -- he 9 didn't talk about it. 10 THE COURT: I thought you said you asked him 11 about that. 12 MR. VICKERY: I didn't. I just discovered it 13 in the middle of the trial, Your Honor. It is a 14 recent article by a Pfizer scientist against the 15 interest of the SSRI manufacturer. 16 MR. SEE: Wait a minute. 17 MR. VICKERY: It literally knocks them out of 18 the park on this. 19 MR. SEE: It's nothing against Lilly because it 20 has nothing to do with Lilly. The man said he hadn't 21 read the article. 22 MS. MANGRUM: It's from the U.K. That's why he 23 hasn't read it. 24 MR. VICKERY: People frequently don't read 25 articles that they get cross-examined on. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2298 1 MR. SEE: I tell you, Your Honor, I want to say 2 this right now, I resent the implication about this. 3 Mr. Vickery has suggested to the Court that this 4 witness has been prepared to falsely deny that he's 5 seen articles, and I just want to tell the Court that 6 is absolutely not true and it's very difficult for me 7 to stand here and listen to him say it. 8 The man did not see the article. I've never 9 seen the article. Mr. Vickery has no foundation for 10 it and he can tell you how important it is to his case 11 and this will break my case and all that, it always 12 comes up every time he wants to get something, but he 13 had an expert on the stand. His expert could have 14 talked about that article during the two or three days 15 that he was on the stand and he didn't do it. 16 He has made no foundation for the article. The 17 man has never read it, and it just doesn't -- he 18 cannot impeach with it because he hasn't read it. 19 MR. VICKERY: I'm not accusing Mr. See saying 20 that he told the witness to falsely deny something 21 that you've not seen. What I'm suggesting is that 22 this witness, on an article that he hasn't seen, he 23 understands, because he's an experienced witness or 24 because he's been told this, you can't be 25 cross-examined about something unless you recognize it PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2299 1 or unless it's already recognized by something else. 2 MR. SEE: That statement is false and I resent 3 it. That is absolutely false. 4 THE COURT: I'm not changing my ruling. 5 (Whereupon, the following proceedings were had 6 in open court in the presence of the jury.) 7 THE COURT: Please proceed, Mr. Vickery. 8 MR. VICKERY: Thank you, Your Honor. 9 Q. I want to show you a couple of things that we 10 previously looked at dealing with the appropriateness 11 of rechallenge, one is a letter from Dr. Beasley. 12 When he wrote his meta-analysis, Dr. Healy wrote a 13 letter criticizing it and Dr. Beasley wrote a 14 response, so what I'm going to show you is 15 Dr. Beasley's response. 16 "We are surprised by Healy and Creaney's 17 characterization of Item 3 of the Hamilton scale for 18 depression as an insensitive measure of suicidality 19 because our data showed that it did distinguish 20 between treatment groups." Do you think that Item 3, 21 that zero to four, is a sensitive measure of 22 suicidality? 23 A. Sensitivity is defined operationally, so it's a 24 statistical term, so if there is a significant 25 difference between treatment groups, it is, by PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2300 1 definition, sensitive. 2 Q. Can you answer it yes or no for me? I just 3 didn't understand that one. 4 A. Yes. 5 Q. Let's go on down. "Healy and Creaney's 6 suggestion of using rechallenge to determine causality 7 of rare events is scientifically appropriate." Do you 8 agree with Dr. Beasley, who works for Lilly, that that 9 is a scientifically appropriate way to look at the 10 issue? 11 A. With appropriate placebo controls, sure. 12 Q. Okay. Let's look at an article. It's a 1992 13 article from Dr. Jick, who we have been talking about, 14 and we're just going to look at the last page of it. 15 They conclude "In view of the close relationship 16 between the indication for a drug use and the events 17 of concern, it is likely to be difficult, if not 18 possible, to demonstrate such an event except perhaps 19 by rechallenge." 20 Do you agree that it is difficult to 21 demonstrate this by clinical trials or epidemiology? 22 A. Again, if the epidemiologic study is well 23 constructed, I think it can actually be sensitive to 24 these events. 25 Q. Now, you know that Dr. Jick is an PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2301 1 epidemiologist, don't you? 2 A. Yes, I do. 3 Q. So when he writes that "it's difficult to do 4 except by rechallenge," do you tend to give him more 5 credence because he is an epidemiologist than, say, 6 you yourself would put in your own opinion? 7 A. Well, I mean, I think that Dr. Jick and I would 8 not disagree on the basic issue. The issue is, how do 9 you construct an epidemiologic trial? This particular 10 paper was based on what's called a sample of 11 convenience which means that it's a sample that he had 12 available to him that had certain data imbedded in the 13 computer files and other data that was not imbedded in 14 that. 15 If you were to construct an epidemiologic study 16 or you had a different data set that addressed some of 17 the things that were missing in his data set, then, 18 you know, you could perhaps have a better, more 19 definitive examination than he did. 20 Q. Okay. Did you ever talk to him or write him 21 about that? 22 A. No, I did not. 23 Q. Do you know the Lexicon of Psychiatry, 24 Neurology, and the Neurosciences? Is that a reputable 25 authoritative source in your field? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2302 1 A. I don't know what it is. 2 Q. Okay. Well, I can't ask you about it then. 3 A. Is it a book? 4 Q. No. Well, I think it is. It's by Frank Ayd, 5 A-Y-D. You see the cover? 6 A. Um-hum. 7 Q. Is that something you recognize as an 8 authoritative source in your field? 9 A. Again, I've never seen the book. 10 Q. Okay. How about the Australian and New Zealand 11 Journal of Psychiatry. You mentioned a New Zealand 12 study. Do you recognize that as an authoritative 13 source in your field? 14 A. Well, I mentioned a New Zealand study, but I 15 think that it was actually published in the archives 16 of general psychiatry, but sure. Yeah, I've consulted 17 the Australian and New Zealand Journal on occasion. 18 Q. Okay. Well, let's look at one of theirs. 19 MR. VICKERY: If I may approach, Your Honor? 20 THE COURT: You may. Let's take a 15-minute 21 break while he's looking at that. Please be back at 22 five to eleven. 23 (Whereupon, a recess was taken from 10:40 a.m. 24 to 11:05 a.m.) 25 THE COURT: The Court will meet with counsel at PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2303 1 side bar. 2 (Whereupon, the following proceedings were had 3 at side bar out of the hearing of the jury.) 4 THE COURT: During the intermission, 5 Mr. Vickery offered the article and the material is 6 peer reviewed, so I will allow him to cross-examine. 7 MR. SEE: I'll just note, Your Honor, with 8 respect, being peer reviewed is not the test. 803.18 9 says it has to be sponsored, recognized by someone 10 that's an authoritative source, and the fact that it 11 says peer reviewed doesn't do that. 12 THE COURT: Okay. And you can cross-examine 13 Dr. Healy on the same basis. 14 MR. VICKERY: Judge, I need to alert you, in 15 the copying, there were two pages from the article 16 that weren't in the witness' copy and Mr. See's and we 17 have run to get the copies right now. We got it back 18 a minute ago. I gave the witness a highlighted copy. 19 If you want, one thing we might do, I can finish up 20 subject to that, and give him the lunch hour to look 21 at it. 22 THE COURT: Does he need more time to look at 23 it? 24 MR. SEE: Well, he's trying to read it as he's 25 sitting here right now. He was trying to get on an PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2304 1 airplane after lunch. 2 MR. VICKERY: What time is his airplane? 3 MR. SEE: It's 1:30 or 1:40. 4 MR. VICKERY: Okay. Then I guess we better do 5 it now. 6 THE COURT: Okay. 7 MR. VICKERY: We'll have those two pages in 8 just a minute. 9 (Whereupon, the following proceedings were had 10 in open court in the presence of the jury.) 11 Q (By Mr. Vickery) Okay, sir. Doctor, we're 12 going to -- there's just a couple of other things I 13 want to ask you and then we're going to look at the 14 Lane article. We're missing two pages, as I told you 15 when I handed that out, and they're being copied right 16 now. 17 Before we get to that, let me just ask you if, 18 in reviewing the scientific literature on these 19 issues, you have read and considered the following 20 articles: Ian Oswald, "Fluoxetine and Suicide" in the 21 British Medical Journal? 22 A. I don't know that I could tell you just off the 23 titles themselves. I'd probably have to see the 24 article and look at it. 25 Q. Okay. How about Gore and Isacsson, "The Use of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2305 1 Antidepressants Among People Committing Suicide in 2 Sweden," does that ring a bell with you? 3 A. I believe, in discovery, I actually was asked 4 to give a number of the articles I had reviewed and I 5 did do that. 6 Q. Yes, sir, you did, and there are a couple that 7 you provided in discovery that I want to ask you 8 about, but let me ask it to you this way: Have you 9 read things since discovery? 10 A. Yes, sir. 11 Q. Since your deposition in this case that you 12 haven't told us that you've read? 13 A. Yes. 14 Q. Okay. That's kind of why I wanted to go 15 through this list with you. Both of those are 16 published in the British Medical Journal. Is that 17 kind of the premier medical journal in the United 18 Kingdom? 19 A. Are you referring to Lansit? 20 Q. Is Lansit the top one? 21 A. I don't know how you judge it. It's sort of 22 apples and oranges. 23 Q. Are those two sort of the two premier ones? 24 A. I think so, yeah. 25 Q. Well, have you read the April 9, 1994 article PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2306 1 in Lansit called, "Artificial Paradise Incapsulated"? 2 A. No, I have not. 3 Q. How about do you know, either personally or by 4 reputation, a Dr. Prakash Marsand? 5 A. No, I do not. 6 Q. Have you read his article on "Suicidal Ideation 7 Related to Fluoxetine or Prozac Treatment" in The New 8 England Journal of Medicine? 9 A. An article? 10 Q. It's a paper, article. The title -- 11 A. Perhaps it's a letter to the editor? 12 Q. Yes, it is. That's right. Thank you for 13 reminding me. It is a letter to the editor. Have you 14 read that? 15 A. I don't know. You'd have to show it to me and 16 I can tell you. 17 Q. Let me see if I can jog your recollection. 18 This is the one that involves 15 cases that 19 Dr. Marsand and his colleagues -- 20 MR. SEE: Your Honor, I object to the testimony 21 of counsel and ask that it be stricken. 22 THE COURT: Sustained. You better show him the 23 letter to the editor. 24 MR. VICKERY: Okay. I will do that 25 momentarily. In fact, I will do that right now, Your PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2307 1 Honor. May I approach? 2 THE COURT: You may. 3 Q (By Mr. Vickery) I've handed you a letter to 4 the editor by Dr. -- I'm going to mispronounce his 5 name, Dewand and Dr. Marsand. Is that the letter to 6 the editor you were talking about, sir? 7 A. Again, this is actually a very hard thing to 8 read. Do you have a better copy than this? 9 Q. No, sir. That's the best I can do for you. 10 A. I have not seen this before. 11 Q. Okay, sir. So you did not consider this in 12 arriving at your opinions? 13 A. That's correct. 14 Q. Do you recognize the Journal of Family Practice 15 as a reliable authority in your field? 16 A. Again, I mean, I don't know how you make that 17 assessment. I judge articles on the basis of 18 scientific methodology and the Journal of Family 19 Practice is not a journal that I'm familiar with. 20 Q. Do you know by reputation Dr. Prakash Marsand? 21 A. I believe you asked me that, and I do not. 22 Q. You do not know him, okay. Do you conclude, 23 from this letter to the editor, that there are 24 additional cases that physicians who are practicing 25 have looked at and believe that Prozac was causing PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2308 1 their patients to become suicidal? 2 A. Can I just ask you, I thought this was the New 3 England Journal of Medicine that we were going to look 4 at a letter to the editor. 5 Q. No. 6 A. Was I confused about that? 7 Q. You or I were. 8 A. I see. I'm sorry, what are you asking me at 9 this point? 10 Q. Let me clear up that confusion for you. What I 11 think I asked you about was an article that Marsand 12 wrote called, "Suicidal Ideation Related to Fluoxetine 13 Treatment" that was in The New England Journal of 14 Medicine. Now, first of all, is that -- 15 A. Again, are you -- when you used the term 16 article, are you referring to a letter to the editor? 17 Q. Don't know. 18 A. There's a significant distinction between the 19 term "article" and "letter to the editor." 20 Q. When someone gives a title like that, "Suicidal 21 Ideation Related to Fluoxetine Treatment," that's 22 usually indicative of an article, isn't it? 23 A. No. In fact, here we have another letter to 24 the editor that has a title to it. 25 Q. Okay. Well, let me ask you this: How about a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2309 1 1995 book by a Dr. Anderson called, "Serotonin and 2 Suicidality, The Impact of Prozac Administration" or 3 fluoxetine administration, "Acute Neurobiological 4 Effects." Did you consider that book in arriving at 5 your opinions that the scientific evidence is clear 6 and there is no controversy? 7 A. I've restricted my review of the literature to 8 published journal articles. 9 Q. A book -- is a book lower on the food chain in 10 scientific literature than an article? 11 A. Well, it depends on how you judge that, but 12 journal articles have to meet editorial review and 13 peer review in a way that most books do not. 14 Q. How about an article in the Journal of 15 Emergency Medicine by Dr. Michael Tueth, T-U-E-T-H, 16 called, "Revisiting Prozac and Suicidal 17 Preoccupations," did you consider that one, a 1994 18 article, prior to arriving at your opinion that the 19 controversy was all over? 20 A. Again, I believe what my testimony was was that 21 the controversy existed for a period of some years in 22 the early nineties and that it is now 1999, and the 23 controversy is over. 24 Q. Okay, sir. Well, let's turn then to 1998, 25 okay, six months ago, but I need to highlight this for PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2310 1 you and your counsel, so just bear with me. 2 MR. VICKERY: May I approach, Your Honor? 3 THE COURT: You may. 4 Q (By Mr. Vickery) Doctor, I'm going to give 5 you the missing pages. I apologize for that. It is 6 196 and 208. You may want to insert them in the 7 proper place in the article and then we're going to 8 look at it. 9 Okay, sir. We'll start on Page 1 and we're 10 just going to look at the highlighted portions. You 11 see the title is, "SSRI-Induced Extrapyramidal Side 12 Effects and Akathisia, Implications for Treatment." 13 It's by Dr. Roger Lane at Pfizer. 14 A. Do we know that he's a doctor? 15 Q. Well, I'm sorry. Let's look. Let's look back 16 in the back and maybe it will tell us. It doesn't 17 say. It just says R.N. Lane at Pfizer. Does he have 18 to be a doctor for us to -- 19 A. I don't know. You called him a doctor. I was 20 wondering what you based it on. 21 Q. I made a mistake. I thought he was. Okay. 22 Now, Ms. Barth, just zoom in on the highlights if you 23 would. The first category is, "SSRIs and 24 EPS/Akathisia." We have heard the term extrapyramidal 25 symptoms or extrapyramidal used. Do you believe that PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2311 1 akathisia is a form of extrapyramidal reaction? 2 A. Yes, I do. 3 Q. Okay, sir. So if you will turn over to 193 4 with me. It says, "SSRIs and akathisia: One of the 5 most serious extrapyramidal symptoms reported with the 6 SSRIs is akathisia," and there's a table. And then 7 down at the bottom of that, it says, "SSRI-induced 8 akathisia is a relatively rare event, but it's 9 frequently unrecognized when it does occur. Following 10 a recognized" and then it goes on talking about 11 paroxetine or Paxil-induced akathisia. Now, you agree 12 that it is relatively rare, do you not, sir? 13 A. Yes, I do. 14 Q. But you disagree with them that it's 15 unrecognized because, from the demonstration you gave 16 us yesterday, anybody could recognize that, right? 17 A. No, I don't believe I ever said that it's not 18 unrecognized. It can be unrecognized. 19 Q. Okay. So you think that Mr. Forsyth may have 20 had it and people may not have recognized it? 21 A. No, I don't think he had. 22 Q. Why? Because people didn't recognize it? 23 A. That's correct. It wasn't there. 24 Q. Well, I'm confused. If he can have it and go 25 unrecognized, how can you say -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2312 1 A. No. I said that in clinical practice, it can 2 go unrecognized, but we have a good description of the 3 way in which Mr. Forsyth was for the whole week of his 4 hospitalization. We know a number of the ways in 5 which he interacted with others. We know he slept 6 well. We know he was pleasant and cooperative. We 7 know he said that he had decreased anxiety, so I -- 8 Q. Do we know that -- 9 A. It's not that in the world at large akathisia 10 can't go unrecognized, sure, but that's not relative 11 to the case at hand. 12 Q. Do we know if his toes were wiggling? 13 A. If his toes were wiggling? 14 Q. Yes. 15 A. I didn't see any record that his toes were 16 wiggling in the medical record. 17 Q. My toes are wiggling right now, can you tell 18 that? 19 A. No, I can't. 20 Q. And in the -- the reason I asked this, in one 21 of the tables here, they report that as one of the 22 objective movements that can be associated with 23 akathisia. 24 A. As one of the movements that can be associated. 25 Q. Right. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2313 1 A. That by itself, I would suggest to you, is not 2 sufficient for the diagnosis, and I think that your 3 assumption that you can have just that and call it 4 akathisia is erroneous. 5 Q. Well, let's read on what Dr. -- Mr. Lane or 6 whoever wrote this said, "The precise definition of 7 akathisia is a matter of controversy." And you 8 disagree with him on that because you said there's no 9 controversy, right? 10 A. Well, I'm telling you what the Diagnostic and 11 Statistical Manual description for the diagnosis of 12 akathisia is. That's the agreed upon standard for the 13 diagnosis. If you want to say that akathisia is 14 something that no one can see and is hard to 15 distinguish from just pure anxiety without a motor 16 component or an invisible motor component, I would say 17 I have to disagree with that definition of akathisia. 18 Q. That's what Dr. Healy said and that's why I'm 19 showing you this -- 20 A. Well, I think Dr. Healy misunderstands the 21 term. 22 Q. Well, let's read on. They say, "It's a matter 23 of controversy as is the relative importance of the 24 objective and subjective aspects of the disorder. Is 25 akathisia a movement disorder or an intense and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2314 1 uncomfortable mental state characterized by dysphoria, 2 an inner agitation, that builds to a level sufficient 3 to compel non-specific motor manifestation? 4 Shlevdef," if I don't mispronounce his name, "gives an 5 excellent description of the manifestations of 6 akathisia, Table 4. The most outstanding feature of 7 akathisia is the subjective distress." Do you agree 8 with that or not? 9 A. It is one component part. It's certainly a 10 necessary part, but it's not sufficient. 11 Q. Let's look at Table 4. Have you read this 12 Sachdev article that he cites here? 13 A. No, I have not. Where did that appear? 14 Q. We'll have to look at the end to see. "Table 4 15 shows signs and symptoms of akathisia, Sachdev, 1995." 16 Do you see under objective signs, two of the ones are 17 inability to keep toes still and semi-purposeful hand 18 arm movements. 19 Now, has it been related to you, sir, that the 20 testimony of Kim Forsyth was that when Mr. Forsyth was 21 on his way to Castle Medical Center, his hands were 22 fidgety? 23 A. I believe that I heard that that was -- well, I 24 guess I understand two things, if that's the testimony 25 that came from Mr. Forsyth's daughter? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2315 1 Q. Daughter-in-law. 2 A. Daughter-in-law. It was my impression that her 3 original deposition testimony and her later testimony 4 differed in terms of what her observations were. 5 Q. She did not mention, in her original deposition 6 testimony, that she saw this, you're absolutely right. 7 Does that cause you to believe she's being untruthful? 8 A. No. 9 Q. Okay. But that has been related to you, that 10 there was some hand movement? 11 A. That's correct. 12 Q. Okay, sir. 13 A. Again, in this table, I think it's incorrect to 14 assume that you can have just that one thing. If 15 you'll notice, and you didn't reflect on the other 16 movements that are noted as well, shifting body 17 position in chair, semipurposeless, purposeless in the 18 leg and feet movements. 19 Q. How many do we have to have? 20 A. Well, that's a good question. I would suggest 21 that you need to have several of them. 22 Q. Let me ask you about the ones under standing. 23 That was just under sitting, but down under standing, 24 you see where it says, "Shifting weight from foot to 25 foot and/or walking on the spot? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2316 1 A. Right. 2 Q. I'm shifting weight from foot to foot now? 3 A. That's correct. 4 Q. And that's far less prominent than the little 5 demo that you did for us yesterday. 6 A. Well, if you kept doing that for hours on end, 7 which is what you see in akathisia, I think it would 8 be noticeable. 9 Q. Did you see in the records -- Dr. Healy 10 testified and the records showed that Mr. Forsyth was, 11 as I believe he said, on the move. He was up and 12 about while he was in Castle. Did you see that? 13 A. I'd have to be shown the exact reference, and 14 what that means, I don't know. 15 Q. Okay, sir. I want to go back to this table, 16 Table 2, Ms. Barth. Let's keep these in order. Now, 17 Table 2 lists -- I'm just going to have to read these 18 out to you, Doctor. Lists all of the articles that 19 are literature reports of SSRI-induced extrapyramidal 20 side effects, and what I want to do is just read the 21 names of these people and tell us if you considered 22 these articles in arriving at your opinion that there 23 was no controversy in the scientific literature. 24 A. Can I just ask a -- 25 MR. SEE: Let me just object first. The PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2317 1 question is vague if it refers to akathisia because 2 that's not what the table refers to. 3 Q (By Mr. Vickery) Okay. Mr. See is absolutely 4 right. Let me turn to Table 3. Would you do that, 5 Doctor? Table 3, do you see those literature reports 6 of SSRI-induced akathisia? And so what I'd like to do 7 is just ask you if you considered these articles. The 8 Adler and Angress article in 1995? 9 A. Again, you know, I would have to look at each 10 individual article to tell you. I have a stack that's 11 about 2 feet high of articles pertinent to the issue 12 of movement disorders and SSRIs. I'd have to look at 13 the specific article to tell you whether I saw it or 14 not. 15 Q. You can't tell us without looking at that? 16 A. Not in these case reports, I can't. I can tell 17 you with the larger scale experimental studies, the 18 more prominent studies. 19 Q. Do you see that there's a page and a half of 20 listing of different articles that Lane says involve 21 SSRI-induced akathisia? 22 A. And he didn't reflect any studies that were 23 done looking at SSRI-induced akathisia. He only 24 reports the ones that were positive is what you're 25 saying? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2318 1 Q. No, sir. I'm saying he's giving us literature 2 reports of SSRI-induced akathisia. 3 A. But he hasn't reported any studies that show 4 negative findings. 5 Q. There's been no studies to study the issue. 6 A. I beg to differ. There are several prospective 7 studies which have been looking at SSRI-induced 8 akathisia. 9 Q. Are you talking about Warshaw and Leon? 10 A. Yes. 11 Q. Those involve 600 people each? 12 A. Yeah, about that, 640, 650 people each. 13 Q. Okay, sir. Well, let me just mention to you 14 then from this list the ones that Dr. Tollefson in his 15 article cited. Hamilton and Opler in '92, did you 16 read that one? 17 A. Again, I would have to look at the -- you'd 18 have to show it to me to tell you. 19 Q. How about the Lipinski articles in '89, how 20 about those? 21 A. Yeah, I've seen -- I don't know which ones, but 22 I've seen some Lipinski articles. 23 Q. The Rothschild and Loch article in '91? 24 A. Yes, I have seen the Rothschild. 25 Q. Okay. Now, we're back on 196, and we just PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2319 1 heard about Sachdev, and we'll move on down. "Almost 2 all patients describe a feeling of inner restlessness, 3 especially if this description is suggested to them 4 and this may be referred to" I'm sorry, "this may be 5 referred to the mind or the body or both, but has a 6 characteristic reference to the lower limbs." Now, I 7 guess you disagree that it can be either or, it must 8 include the body as well as the mind. Is that your 9 opinion? 10 A. No. It's the opinion actually of the 11 Diagnostic and Statistic Manual that has defined the 12 condition, so to get a diagnosis of akathisia in the 13 United States, according to the DSM-IV, you do have to 14 have both conditions. It is not something that I'm 15 making up. 16 Q. The DSM-IV lists, in the operative portions, 17 that it is talking about neuroleptically-induced 18 akathisia, doesn't it? 19 A. And it says, also, that antidepressant-induced 20 akathisia is equivalent to neuroleptic-induced 21 akathisia. 22 Q. I know it does in the verbiage, but that's not 23 in the diagnostic part, is it? 24 A. I don't know what you're suggesting, that one 25 not read the section on defining it? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2320 1 Q. Well, let's move on. "A non-agitated 2 depression may appear to convert to an agitated form 3 if fluoxetine" or Prozac "induced akathisia is 4 produced. In fact, in one group's opinion, quote, 5 agitated depression and severe Prozac-induced 6 akathisia are indistinguishable and very likely share 7 the same pathophysiology." And they cite the Lipinski 8 article that you said you read, right? 9 A. I said I read one of the Lipinski articles or a 10 couple of them. I don't know which one '89 is. 11 Q. Dr. Reus, can you help us with pathophysiology? 12 What does that mean? 13 A. It means the underlying biologic mechanisms. 14 Q. Okay. And I think you're on record, at least, 15 in public statements saying that the underlying 16 pathophysiological methods of SSRI drugs are not well 17 understood, aren't you, sir? 18 A. That's correct. 19 Q. We don't know how these drugs really work. We 20 have ideas how they're supposed to work, but we really 21 don't know all the systems they work on, do we? 22 A. That's correct. 23 Q. They may work on the dopamine system, true or 24 not? 25 A. It may involve dopamine, yes. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2321 1 Q. Is that a different neurotransmitter from 2 serotonin? 3 A. Yes, it is. 4 Q. And it may work on the norepinephrine 5 neurotransmitter. True or false? 6 A. It may utilize that system, yes. 7 Q. Is that the same thing as the neurodonergic 8 system? 9 A. Yes, it is. 10 Q. And is there something about Prozac working on 11 those other two neurotransmitters, in addition to 12 serotonin, that gives rise to the possibility that it 13 causes akathisia? 14 A. I don't know that we know exactly the 15 pathophysiology of akathisia either and, in fact, any 16 of the antidepressant drugs can cause akathisia, so 17 again, there are very different molecules. They work 18 on very different neurotransmitter systems and yet, 19 they can all cause akathisia. 20 Q. Okay, sir. Let's look at 198 now, where it 21 says that "Akathisia has been reported in patients 22 with panic disorder or marked anxiety who were 23 initiated on the SSRI, and it gives us several 24 references, the Hamilton and Opler study, Satterlee, 25 Olivera as late as 1997. This is exactly what PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2322 1 Mr. Forsyth had, isn't it? He had anxiety first in 2 November and got Xanax for that, correct? 3 A. That's correct. 4 Q. And he had had a couple panic attacks a couple 5 of different times, hadn't he? 6 A. Well, I think it's unclear as to whether they 7 were true panic attacks or not. 8 Q. Did he have things that his doctors thought 9 were perhaps panic attacks? 10 A. Well, I think one doctor thought that they were 11 panic attacks. Again, I don't know if he fulfilled 12 the full criteria for a panic attack. 13 Q. So you don't know one way or the other? 14 A. Well, I think that the doctor that reviewed the 15 history with him ended up with a diagnosis of anxiety 16 disorder not otherwise specified. 17 Q. "It has been suggested that SSRI-induced 18 akathisia may be associated with the emergence of 19 egodystonic suicidality," and there they cite 20 Lipinski, Rothschild, and Loch and Hamilton and Opler. 21 Do you agree that it is associated with egodystonic 22 suicidality or not? 23 A. I disagree with the emergence of. 24 Q. You think it had to be there before? 25 A. That's correct. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2323 1 Q. All right. "The most consistent factor 2 implicated in these anecdotal accounts of rare adverse 3 reactions involving suicidal ideation and behavior 4 during Prozac treatment was the development of 5 akathisia with agitation, restlessness, and 6 dysphoria," and they cite Power and Cowen. Now, have 7 you read Power and Cowen? 8 A. Again, you'd have to show me the article and 9 I'd have to look at it. 10 Q. And then they talk about Teicher and we've 11 talked about Teicher enough. "It may be less of a 12 question of patients experiencing Prozac-induced 13 suicidal ideation than patients feeling that death is 14 a welcome result when the acutely discomforting 15 symptoms of akathisia are experienced on top of 16 already distressing disorders." Now, you say that, 17 but you qualify it by saying they had to have thought 18 of suicide first; is that true, sir? 19 A. Yes. Is Power and Cowen in the table? I don't 20 see it. 21 Q. I don't know, and I'm sorry, I don't mean to be 22 disrespectful, but I'm going to get in trouble with 23 the judge if you ask the questions and I answer them. 24 A. You asked me about Power and Cowen and so I was 25 looking to see if I could remember the case. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2324 1 Q. Okay. I appreciate that, but we need -- I need 2 to ask the questions and you need to answer them, if 3 you will. 4 Now, tell me, do you believe that Mr. Forsyth, 5 from your review of all the materials, that 6 Mr. Forsyth had had any suicidal thoughts before he 7 took Prozac? 8 A. Yes. 9 Q. Okay. So even if we accept your view that that 10 has to be present first, it was present in this case, 11 wasn't it? 12 A. That's correct. 13 Q. And so would you agree then that if it was 14 present first, and you understand we say not, because 15 none of the doctors saw it, you know that, don't you? 16 MR. SEE: Your Honor, I object again to 17 Mr. Vickery giving testimony and I ask that it be 18 stricken. 19 THE COURT: Sustained. 20 Q (By Mr. Vickery) If, in fact, he had thought 21 about it before Prozac, and then he had the acute 22 discomforting symptoms of akathisia on top of that, 23 that's the very kind of thing that would trigger 24 violence or suicide, isn't it? 25 MR. SEE: Objection. It's an incomplete PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2325 1 hypothetical and it assumes facts that are not in 2 evidence. 3 THE COURT: Rephrase the question, Mr. Vickery. 4 Q (By Mr. Vickery) If Mr. Forsyth had suicidal 5 ideation first and then if he got a Prozac-induced 6 akathisia, is that, in your opinion, the very kind of 7 thing that would lead him to violent or suicidal 8 behavior? 9 MR. SEE: Objection. It's an incomplete 10 hypothetical and it assumes facts not in evidence. 11 MR. VICKERY: Your Honor, I don't know how to 12 make it complete and it assumes the facts that Mr. See 13 has suggested. That's Mr. See, not me -- 14 THE COURT: I'll allow you to ask the 15 hypothetical question. You may go ahead. 16 MR. VICKERY: Thank you, Your Honor. 17 Q. I would like for you to assume that he did, 18 that he was suicidal first, if we believe that, and 19 then got a Prozac-induced akathisia, is that the kind 20 of thing that would trigger violent or suicidal 21 behavior? 22 MR. SEE: Again, Your Honor, my objection is to 23 the form of the question. It assumes a fact not in 24 evidence. 25 THE COURT: It's a hypothetical. I'll allow PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2326 1 it. 2 THE WITNESS: Well, in this particular case, 3 even if you assume that akathisia occurred, he was 4 already being treated for akathisia with propanolol, 5 so therefore, I do not think that he would have had 6 akathisia or sufficient to exacerbate any suicidal 7 ideation. 8 Q (By Mr. Vickery) Let me ask you about him 9 being treated with propanolol. Is there any 10 indication to you, from the medical records, that it 11 was explained to him just how important it would be 12 for him to keep taking those pills? 13 A. Well, I mean, we know he suffered from anxiety 14 and was prescribed Xanax for anxiety, and I don't 15 think there is any evidence that he didn't take it for 16 anxiety. 17 Q. Don't we also know that he was just really 18 afraid of drug addiction because of his prior alcohol 19 problems? 20 A. He was afraid of addiction to Xanax. There's 21 no indication that I know that he was unwilling to 22 take the other medications that he was given. 23 Q. Okay. Now, we've already talked about 24 Rothschild, so let's go on. Over on Page 200, 25 discussing how doctors should manage patients who have PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2327 1 this, it says, "Loss of therapeutic effect after 2 initial response, particularly if accompanied by side 3 effects of agitation, restlessness, and anxiety, may 4 be due to serotonergic overstimulation and may be 5 managed by dose reduction, possibly after a temporary 6 treatment discontinuation rather than by a dosage 7 increase." Now, we're getting here to something that 8 we haven't heard a thing about, serotonergic 9 overstimulation. Do you believe, sir, that there is a 10 phenomenon with SSRI drugs called serotonergic 11 overstimulation or sometimes called the serotonin 12 syndrome? 13 A. Yes, I do. 14 Q. Okay. And would you just explain for the jury 15 what that is? 16 A. Well, it's a very serious life-threatening 17 syndrome that's associated with -- when you have, 18 usually, very high doses of a serotonergic drug or 19 combinations of serotonergic drugs together, and it's 20 a condition where you have usually a very high fever, 21 usually disturbance in consciousness, hard to think, 22 sort of a delirious-like condition. Oftentimes 23 individuals can be quite agitated, very brisk 24 reflexes, they look very sick, but it is also 25 something that can be mistaken for sort of psychotic PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2328 1 agitation in individuals that previously presented 2 with psychosis. 3 Q. So that we're real clear on this, Doctor, this 4 is from having too much serotonin in the brain as 5 opposed to too little? 6 A. Well, it's not just the brain. It's throughout 7 the body at large. 8 Q. But it's too much rather than too little, 9 right? 10 A. That's correct. 11 Q. So the fact that serotonin -- that Prozac 12 increases the available serotonin can -- it can 13 increase it too much to the point that we get a 14 serotonin syndrome, correct? 15 A. Yes. 16 Q. Okay. "Now, treatment strategies found useful 17 for SSRI-induced akathisia are illustrated in Table 8. 18 Akathisia should be managed by discontinuation of the 19 SSRI drug, dosage decrease, or if close clinical 20 monitoring is possible by continuation of the SSRI 21 with the addition of propanolol, short-term 22 benzodiazepine treatment, or possibly low-dose 23 Mianserin." 24 Now, propanolol, you already pointed out, is 25 what he was getting, right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2329 1 A. That's correct. 2 Q. That's the Inderal? 3 A. That's correct. 4 Q. Was Xanax a benzodiazepine? 5 A. Yes, it is. 6 Q. Okay, sir. "Mild cases may resolve or continue 7 treatment. However, symptoms of akathisia have been 8 noted to persist for over one year in patients 9 receiving Prozac suggesting that at least some 10 patients' tolerance to this side effect may not 11 develop." Let me ask you about that. Do you believe 12 that different people react to Prozac differently? 13 A. That's true for every drug. 14 Q. Okay, sir. Here it says, 15 "Antidepressant-induced akathisia is reversible upon 16 discontinuation or dose reduction of the drug," and it 17 cites Rothschild and Locke, Hamilton and Opler, 18 Bertschy and Vandel, LaPorta, Bangs, Coulter and 19 Pillans and Hoaken. Those are all instances of 20 dechallenge, are they not, where the drug is taken 21 away and the akathisia goes away? 22 A. Yes. 23 Q. Okay. 24 A. Well, I'd have to say I'm not so sure about 25 dose reduction. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2330 1 Q. You think you have to take it away entirely? 2 A. Well, if you're talking about dechallenge as 3 the definition, I think you would have to take it away 4 completely. 5 Q. Good point. And one of the reasons that it has 6 to be taken away completely with Prozac is because it 7 remains in your system a long time? 8 A. You'd have to take away any drug. It's not 9 just Prozac. 10 Q. Okay. Now, on Page 203, they asked a question, 11 is akathisia a serotonin syndrome? Now, serotonin 12 syndrome is what we were just talking about, having 13 too much serotonin, right? 14 A. That's correct. 15 Q. Do you believe that akathisia can be caused by 16 having too much serotonin? 17 A. I don't think there's any evidence to conclude 18 one way or the other about it. 19 Q. So let's look at what they say and tell me if 20 you agree with them or not. They say that 21 "SSRI-induced akathisia may represent a form of 22 serotonergic overstimulation or serotonin toxicity." 23 They cite Cane from '92. Do you know that article? 24 A. Is this Eric Cane? 25 Q. Don't know. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2331 1 A. I don't know. I'd have to see the article. 2 Q. They say that "Agitation and restlessness and 3 insomnia are commonly seen in cases of the serotonin 4 syndrome and may be early prodromal signs of the 5 syndrome." Now, those are the very things that you 6 told us earlier today, nervous, anxiety, and insomnia 7 caused people to drop out of the Prozac clinical 8 trials, aren't they? 9 A. That's what was reported as cause for 10 discontinuation, yes. 11 Q. Reported by Eli Lilly in the product label? 12 A. As part of the psychiatric component. There 13 were other reasons, GI reasons, things like that, that 14 caused people to drop out as well. 15 Q. Before you leave that, Ms. Barth, they're 16 discussing those things as being markers of akathisia, 17 and we know about 212 people dropped out of the 18 clinical trials because of those three things. Is it 19 fair for us to say, well, those people that dropped 20 out of the clinical trials must have had a mild form 21 of akathisia? 22 A. I think the statement says that they are 23 commonly seen in cases of serotonin syndrome. It 24 doesn't say that they are commonly seen in cases of 25 akathisia, as I read that sentence. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2332 1 Q. Well, how do you read this sentence? 2 "SSRI-induced akathisia may represent a form of 3 serotonin overstimulation or serotonin toxicity." 4 A. Right. 5 Q. Isn't it one in the same? 6 A. No, it's not the same. That's the point 7 they're trying to say may represent the form of 8 overstimulation, and they go down underneath and say 9 are commonly seen in cases of the serotonin syndrome, 10 but they are not saying that they are common signs of 11 akathisia. 12 Q. Are they -- do you believe that agitation, 13 restlessness, and insomnia are common signs of 14 akathisia? 15 A. I think agitation and restlessness are. I 16 think insomnia is more of a speculation. 17 Q. Okay. Lower in that same column, they said, 18 "The code administration of serotonergic 19 medication" -- is serotonergic just something that 20 increases serotonin? 21 A. That's correct. 22 Q. Like an SS -- 23 A. Well, it doesn't necessarily increase 24 serotonin. It increases serotonergic effect or 25 activity. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2333 1 Q. Throughout the body? 2 A. Not necessarily throughout the body. 3 Q. Okay. I'm sorry, I thought you said a minute 4 ago it was throughout. Is it localized in the brain 5 or -- 6 A. No. I said serotonin syndrome involves 7 serotonergic receptors throughout the body. 8 Q. Incidentally, how many different serotonin 9 receptors are there in our body? 10 A. Fifteen at last count. 11 Q. And how many of those 15 serotonin receptors 12 are blocked by Prozac? 13 A. Are blocked? 14 Q. Yes, sir, the reuptake. That's how it works, 15 isn't it? 16 A. Well, it's not the receptor that's blocked. 17 Q. What is it? 18 A. It's the transporter protein that's blocked. 19 Q. How many transport sites are there for 20 serotonin? 21 A. Just one. 22 Q. And is that the only one that's blocked by 23 Prozac? 24 A. That's correct. 25 Q. But it also affects both the dopamine and the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2334 1 norepinephrine sites, doesn't it? 2 A. Well, I don't think in -- not in a receptor 3 sense, no. 4 Q. In what sense then? 5 A. Well, I mean, indirectly by amplifying 6 serotonin, you can have indirect effects on other 7 neurotransmitter systems. 8 Q. Okay. I think I followed that. Thank you. 9 Turn over to 205, if you would. Here under the 10 category SSRI, SSRI, that stands for selective 11 serotonin reuptake inhibitors, right? 12 A. That's correct. 13 Q. EPS is extrapyramidal symptoms, right? 14 A. That's correct. 15 Q. And akathisia. "They say that Prozac is the 16 least selective amongst the SSRIs for the reuptake 17 inhibition of serotonin relative to NA," and that's 18 for norepinephrine, "but noradrenaline -- I can't say 19 that word. Would you help me, Doctor? 20 A. Noradrenaline, that's correct. 21 Q. Okay. Thank you, sir. Do you agree with them 22 that Prozac is the least selective among the SSRIs? 23 A. Well, it depends on which SSRIs you're talking 24 about. If you're talking about compared to sertraline 25 or compared to paroxetine or compared to satalapran, I PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2335 1 would say yes. 2 Q. Now, we've used their common names here, Zoloft 3 and Paxil and the other one is -- 4 A. Solexa. 5 Q. Okay, sir. Now, here we get to this thing 6 you're going to try to educate us about, SSRIs and 7 5-HT2c receptors. Can you tell us what those are? 8 A. That's one of the 15 receptors. 9 Q. So this is not the reuptake or transport site, 10 this is a receptor? 11 A. That's correct. 12 Q. All right. They say that "Prozac has affinity 13 for the 5-HT2c receptor as suggested in some in vitro 14 and in vivo studies," and they cite Wong and Jeng and 15 Wood and Tullock and Palifonocki. Would you explain 16 for us, when it says affinity, does that mean it likes 17 it? 18 A. Yes. 19 Q. And in vitro, what does that mean? 20 A. In tissue studies. 21 Q. That's like test tubes or slides in the lab? 22 A. Um-hum. 23 Q. And in vivo, is that in living people? 24 A. No, it can be in animal studies. 25 Q. Okay. So what's the significance -- first of PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2336 1 all, do you agree that Prozac has an affinity for the 2 5-HT2 receptor site? 3 A. Well, this is where it's still controversial. 4 It's relatively recent work. I think there's some 5 evidence that it has some affinity for the 5-HT2 cite, 6 yes. 7 Q. They say "If Prozac was a weak 5-HT2c receptor 8 agonous, this activity may augment the potential for 9 Prozac to cause side effects of agitation and/or 10 akathisia." A lot of big words in there. Let me ask 11 you, Dr. Reus, if Prozac does have this affinity for 12 this receptor site, it effects that site, do you agree 13 with the author of this paper, that would increase or 14 augment the possibility that it would cause akathisia? 15 A. No, I don't think it's been established yet 16 that the 5-HT2 site is a prime mediator of akathisia. 17 Q. Okay. Next page, 206. Talking about SSRIs, 18 agitation, melancholia, and serotonin overstimulation. 19 "The emergence of symptoms of akathisia could be 20 mistaken for a worsening of depression, especially the 21 conversion of non-agitated depression to an agitated 22 form." Do you believe that akathisia could be 23 mistaken for the depression getting worse? 24 A. Again, akathisia could look like agitated 25 depression in the sense that there's a motor component PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2337 1 and an internal sense of discomfort and restlessness, 2 so if an individual or clinician were not acquainted 3 with akathisia, then they could possibly mistake it -- 4 mistake agitated depression for it. 5 Q. And do you, therefore, believe, sir, that it 6 was important for physicians to be told by Eli Lilly 7 that this drug can cause akathisia in some people and 8 this is what you need to look for? 9 A. Again, akathisia was in the mailing and the 10 initial package insert as we reflected yesterday. 11 Q. Right, but what we reflected yesterday is they 12 said akathisia has happened, but we don't think the 13 drug causes it, and so my question is a little bit 14 different. It is, do you think it was important for 15 Eli Lilly to say, hey, we think our drug probably 16 causes it, look out for it, it's dangerous? 17 A. I don't think at the time that the package 18 insert came out that we were aware, in any way, shape, 19 or form of, you know, the sort of literature around 20 akathisia that we are now. 21 Q. The Lipinski and Opler, and, of course, 22 Teicher, all of those things predate the death of the 23 Forsyths, don't they? 24 A. Right, that's true. 25 Q. Okay. On Page 207, "The product insert for PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2338 1 Prozac" -- and that's talking about the label, isn't 2 it? 3 A. That's correct. 4 Q. -- ..."describes, quote, anxiety, nervousness, 5 and insomnia in 10 to 15 percent of treated patients 6 leading to drug discontinuation in 5 percent." That's 7 the very thing you and I were talking about this 8 morning, correct, sir? 9 A. That's correct. 10 Q. "In a prospective naturalistic study of Prozac 11 in 248 general psychiatric outpatients, the most 12 common events leading to withdrawal of treatment were 13 anxiety and agitation, 4 percent, and then headache, 14 insomnia," and look at this, "aggression 1 percent." 15 If we combine anxiety and agitation with aggression, 16 we've got 5 percent, don't we? 17 A. Yes. 18 Q. And what do you -- what is a prospective 19 naturalistic study? 20 A. Again, you know, these are not -- I don't think 21 you can add these things individually because an 22 individual could have all of them at the same time and 23 be recorded in those. So I don't think you know that 24 they're independent cases. 25 Q. Could be just 4 percent instead of 5 because -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2339 1 A. For anxiety and agitation. Aggression only 2 occurred in one percent. 3 Q. Right. And it could be that the aggression's 1 4 percent is part of the 4 percent that had agitation, 5 is that what you're saying? 6 A. Yes. 7 Q. And it is probably likely, isn't it? 8 A. No, I don't think we know that. 9 Q. Okay. "Mild or subthreshold akathisia may 10 account for these side effects of Prozac." Dr. Reus, 11 what is subthreshold? 12 A. Below the level of a given threshold. 13 Q. Doesn't that mean below the level of clinical 14 detection? 15 A. No, not necessarily. A threshold can be 16 whatever you set it at. 17 Q. Could it mean below the level of clinical 18 detection? 19 A. It could. 20 Q. So if it's used in that context, subthreshold 21 means somebody's got it, but we can't see it, doesn't 22 it, sir? 23 A. Again, I don't know what is meant by that. It 24 could mean it's commonly misdiagnosed or it could mean 25 that it's invisible. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2340 1 Q. Well, let's read on and they'll tell us exactly 2 what it means. "For example, the inner sense of 3 restlessness, criterion for the diagnosis of akathisia 4 might be described by the patient or the clinician as 5 anxiety or agitation. Thus, the side effects may be 6 the milder and more common manifestations of a 7 spectrum of behavioral toxicity at the end of which is 8 overt akathisia." Do you now understand that that's 9 what they were talking about, they're talking about 10 sort of the precursors, if you will, of akathisia, 11 things that aren't manifested by the -- 12 A. So you're saying that it's not akathisia? 13 Q. I'm saying just what they are, that it's the 14 milder manifestations of a spectrum of behavior at the 15 end of which is overt akathisia. That's what I'm 16 saying. Do you agree with them? 17 A. Again, I don't -- I have to go back to what the 18 definition of akathisia is. If you're saying that 19 anxiety, you know, can occur independent of akathisia, 20 of course. But akathisia requires a motor component. 21 Q. That's not what these guys say, is it? 22 A. I don't know what they're saying. They're 23 saying, on one hand, it's all speculation. They're 24 saying that anxiety can occur and, you know, that 25 motor problems can be in -- I mean, I don't know in PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2341 1 that table -- if you go back to the Sachdev table, 2 that implies that there are a constellation of very 3 significant motor events which should be observable. 4 Q. I won't argue that with you, but we've already 5 talked about toes. You can't observe toes. 6 A. Again, I don't think that that's implied as 7 just a sole event. It occurs along with other motor 8 abnormalities. 9 Q. Okay. Turn the page and we'll do the 10 conclusion and we'll be done by lunch here. Ms. Barth 11 referred me back to the table. So let's go back to 12 Table 2, if we may, on Page 195. You see where 13 these -- we can't see it if we do that. This fifth 14 entry down, somebody was getting Prozac that developed 15 something athetoid hand movements. What are athetoid 16 hand movement? 17 A. It's a sinuous sort of slow writhing movements 18 of the hands, like that. 19 Q. Does that sort of sound like what Kim Forsyth 20 was describing with Mr. Forsyth? 21 A. Not from what I heard, no. Athetoid is very 22 distinctive. It's not fidgeting. Fidgeting is faster 23 movements as I understand them. Athetoid is slow 24 sinuous sort of movement. 25 Q. Okay. Wouldn't a person have to be trained to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2342 1 know the difference between the two? 2 A. Well, I don't expect anybody would use the term 3 athetoid, but it's not the same thing as fidgeting. 4 Fidgeting is faster movements. 5 Q. Okay. Down here is someone else, a 12-year-old 6 male, getting 20 milligrams of Prozac a day and he had 7 ticks, eyelid blinking, shoulder hunching, and 8 movements of the abdomen. What is shoulder hunching, 9 like this? 10 A. I don't know. It's not a medical term usually. 11 Q. Okay. But here's someone that the literature 12 reports to be akathisic who doesn't have any movement 13 of their legs? 14 A. Well, we don't know that. This is an 15 abstraction, so we don't have the original report. It 16 has to be noted that this is a Pfizer-sponsored 17 article and all your comments and the comments in the 18 article have been directed against fluoxetine and Eli 19 Lilly, so I think you have to understand this article 20 in that light. 21 Q. You think Pfizer was sort of loading the scales 22 up to compete against Eli Lilly by saying their drug 23 causes it and ours doesn't? 24 A. Well, I note on Page 207 where it says, 25 "Comparative clinical studies have shown that PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2343 1 Sertraline, the Pfizer product, may be associated with 2 fewer of these types of side effects than fluoxetine." 3 So I think that one has to entertain that possibility, 4 yes. 5 Q. Okay. Do you think that the competitive 6 desires of the company to show our drug is better than 7 Prozac would cause a company, like Pfizer, to publish 8 a 20-page article in peer-reviewed journals? 9 A. Well, I think that there's a constant attempt 10 to broaden your market share for a product against 11 competitors in the business world, yes. 12 Q. But, you know, I think I would agree with you 13 if it said, Prozac causes this, but we don't. But 14 when Pfizer says that SSRI drugs, including their own, 15 Zoloft, causes this, that's really kind of contrary to 16 their financial interest, isn't it? 17 A. No, not when they say ours is better and causes 18 it less, which is what they do say in this article. 19 Q. I see. Okay. Well, thanks for pointing that 20 out for us. In the conclusion here, "The rare 21 occurrence of akathisia when SSRIs are administered, 22 even to patients with predisposing factors, points to 23 the fact that certain individuals may have an 24 underlying constitutional predisposition to these 25 SSRI-induced effects." PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2344 1 That's what we talked about before. You can't 2 tell us how anybody in this courtroom would react to 3 Prozac because we would all react differently, right? 4 A. Well, I don't know that everyone would react 5 differently, but people can respond differently. 6 Q. And do you agree with them -- 7 A. I mean, the data would suggest that the 8 majority of people respond predictably in the same 9 way. 10 Q. Okay, sir. They say here, "The syndrome of 11 akathisia has not been clearly defined to date." Now, 12 you disagree with that vehemently even though this was 13 six months ago by a big company like Pfizer, don't 14 you? 15 A. Well, I mean, I can tell you what the 16 agreed-upon operational definitions are. There are 17 people who disagree with the agreed-upon definitions? 18 Sure. 19 Q. And one of those people works for Pfizer, who 20 is -- just so we understand, one of the three big 21 selling SSRI drugs in this country is their drug 22 Zoloft, isn't it? 23 A. That's correct. 24 Q. And they say "Its pathophysiology is far from 25 clear," and you agree with that, don't you? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2345 1 A. Yes, I do. 2 Q. "The subjective components of akathisia are so 3 distinct and overwhelming, that it is doubtful whether 4 akathisia should be classified as a motor disorder." 5 Now, I take it you disagree with that? You think 6 there's got to be motor movement, physical movement? 7 A. Yes. 8 Q. Okay. "It is not yet clear whether the 9 subjective inner restlessness and dysphoria that 10 characterize this condition are sufficient in 11 themselves; that is, without the objective motoric 12 components" -- how do you pronounce that word? 13 A. Motoric components. 14 Q. "Motoric components for its diagnosis." And 15 your point there is? 16 A. That's my point exactly. It is -- except I 17 would be even stronger about it. They say it's not 18 yet clear. I fully agree with them. What they're 19 saying is there's no evidence as to whether subjective 20 inner restlessness and dysphoria that characterize the 21 conditions are sufficient in themselves; i.e., without 22 the objective motor components for its diagnosis. I 23 agree with that. It is not clear. 24 Q. Okay. 25 A. And I don't think that it's appropriate to PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2346 1 diagnose it on this basis. 2 Q. Well, if it's not clear, then why did you give 3 us that demonstration you did yesterday with your 4 legs? Why didn't you just tell us, this isn't clear 5 yet whether that's required or not? 6 A. No, because at this point, the diagnosis 7 requires an objective motor component and a subjective 8 inner state of restlessness, and these people are 9 saying the same thing. 10 MR. VICKERY: Dr. Reus, I have no more 11 questions for you. Thank you, sir. 12 THE COURT: Mr. See. Are you going to need 13 much time? 14 MR. SEE: Probably about 20 minutes. 15 THE COURT: All right. I understand the doctor 16 has an airplane to catch, so I guess we better go 17 ahead. 18 REDIRECT EXAMINATION 19 BY MR. SEE: 20 Q. You have your article here, Dr. Reus, that 21 Mr. Vickery was just asking you about? 22 A. Yes, I do. 23 Q. Okay. Let's try to clarify this. Would you 24 turn to Page 193, and there's a spot there that says, 25 "Definition of terms used in this review," you see PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2347 1 that? 2 A. Yes, I do. 3 Q. Just looking for my magic marker. 4 MR. VICKERY: I'm sorry, Mr. See, where were 5 you? 6 MR. SEE: I'm on Page 193, the Table 1 says, 7 "Definitions of terms used in this review." 8 Q. Would you just read that for us, Dr. Reus? 9 A. "Definition of terms used in this review. 10 Akathisia, a syndrome characterized by an inner sense 11 of restlessness and an inability to sit or stand 12 still." 13 Q. Okay. That's the one we're interested in. So 14 the authors of the article define it as having an 15 inner sense of restlessness, right? 16 A. That's correct. 17 Q. And -- 18 A. An inability to sit or stand still. 19 Q. Okay. Is that consistent with what you told 20 the jury what the definition of akathisia is? 21 A. I believe it is, yes. 22 Q. Now, you're familiar with this book, the 23 DSM-IV? 24 A. Yes, I am. 25 Q. Tell the jury what this book is. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2348 1 A. This is sort of the standard reference, sort of 2 the Bible for diagnostic classification in the United 3 States, and it's actually been adopted in a number of 4 other countries as well, but it represents the 5 categories of conditions and describes each of the 6 conditions that go into what are called mental 7 disorders. 8 Q. And who puts the DSM-IV together? 9 A. The American Psychiatric Association does. 10 MR. SEE: If I may approach the witness, Your 11 Honor. 12 Q. Let me hand you this DSM-IV from the American 13 Psychiatric Association, and I'm going to note, as you 14 tell me, what are the diagnostic criteria for 15 akathisia in that book? 16 A. Well, what it says are, "The research criteria 17 for 333.99" and it's defined as neuroleptic-induced 18 acute akathisia. 19 Q. Okay. 20 A. "A, the development of subjective complaints of 21 restlessness after exposure to a neuroleptic 22 medication." 23 Q. Hold on one second. Let me get that down. The 24 one we have is subjective complaint of restlessness, 25 right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2349 1 A. That's correct. 2 Q. Is there anything else? 3 A. "B, at least one of the following is observed: 4 One, fidgety movements or swinging of the legs." 5 Q. Okay. What's the next one? 6 A. "Two, rocking from foot to foot while 7 standing." 8 Q. What's the next one? 9 A. "Three, pacing to relieve restlessness." 10 Q. What's the next one? 11 A. "Four, inability to sit or stand still for at 12 least several minutes." 13 Q. Okay. So we're clear about this, the diagnosis 14 requires both of these? 15 A. That's correct. 16 Q. Now, you said that that was the criteria for 17 neuroleptically-induced akathisia. What's neuroleptic 18 mean? 19 A. It refers to antipsychotic drugs, principally. 20 Q. Would you turn to the page before the 21 diagnostic criteria there? 22 A. Yes. 23 Q. Maybe I just need to point out. 24 A. I think -- it's the differential diagnosis. 25 Q. Where it talks about SSRI drugs, do you see PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2350 1 that? 2 A. Yes. 3 Q. Would you read that? 4 A. "Serotonin specific reuptake inhibitor 5 antidepressant medications," and this is in bold, "may 6 produce akathisia that appears to be identical in 7 phenomenology and treatment response to 8 neuroleptic-induced acute akathisia." 9 Q. Okay. So what the book says is 10 neuroleptic-induced akathisia looks like this, and it 11 also says that SSRI drugs may induce akathisia that 12 looks just like this? 13 A. That's correct. 14 Q. Okay. And just so we're clear, I think you 15 testified yesterday that the package insert for Prozac 16 warns about akathisia, doesn't it? 17 A. Yes, it does. 18 Q. Could you turn over to Page 196 of this Lane 19 article? There are just a couple of things I'd like 20 you to clarify based on Mr. Vickery's questions. Down 21 at the bottom of the right-hand column, Mr. Vickery 22 read you this quote. He said, "In fact, in one 23 group's opinion, agitated depression and severe 24 fluoxetine-induced akathisia are indistinguishable." 25 Do you see that? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2351 1 A. Yes, I do. 2 Q. Doctor, would you tell the jury what agitated 3 depression looks like? 4 A. It's an inner state of depression, of depressed 5 mood, people feeling very sad, experiencing 6 self-esteem, all the key ingredients of normal 7 depression, hopelessness, but in addition, it has 8 motor manifestations that are characterized by an 9 individual. Most commonly, for example, wringing 10 their hands, pacing about rapidly, they appear visibly 11 distressed and anxious and agitated. 12 So you have really depression plus very severe 13 anxiety at the same time. You usually have severe 14 insomnia associated with it. People cannot get to 15 sleep or stay asleep when they have agitated 16 depressions, and it's a very severe presentation of 17 depression. 18 Q. Now, Dr. Reus, tell us this: From your review 19 of all the medical records regarding William Forsyth, 20 during any of the time that he was taking Prozac, did 21 Mr. Forsyth have agitated depression? 22 A. Not to my reading of the record. He had 23 anxiety components, but he never had the full agitated 24 depression. He never showed the motor signs that are 25 characteristic of agitated depression. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2352 1 Q. Now let me ask you this: Under the definition 2 that's in this Lane article that Mr. Vickery has been 3 asking you about for some time now, using its own 4 definition, did Mr. Forsyth have akathisia during any 5 time that he was taking Prozac? 6 A. No, because he really -- again, in the full 7 week of the hospitalization, with a number of 8 different observed accounts recorded in the medical 9 record, he didn't show signs or symptoms of a motor 10 disturbance that anyone, I think, could call 11 akathisia. 12 Q. And following the diagnostic criteria for 13 akathisia that is in the Diagnostic and Statistical 14 Manual, any time that he was taking Prozac, did 15 Mr. Forsyth have akathisia? 16 A. Again, there's nothing in the record that shows 17 that he did have it, and there are a lot of things in 18 the record that would indicate that he did not have 19 it, and his abilities to participate in the ward 20 milieu, his statements to the ward staff on a number 21 of occasions about how he was feeling, so I would say 22 no. 23 Q. And Mr. Vickery also asked you some questions 24 about something called serotonin syndrome, do you 25 recall that? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2353 1 A. Yes. 2 Q. And you gave some testimony about what that 3 looks like, and my question is, based upon your review 4 of the medical records and looking at the deposition 5 testimony of all the doctors, did Mr. Forsyth, during 6 any time that he was taking Prozac, have serotonin 7 syndrome? 8 A. No, there is no indication whatsoever that he 9 had serotonin syndrome. I mean, he's described as 10 pleasant and cooperative on a number of occasions. 11 He's described as sleeping well. He's described as, 12 you know, feeling less anxious. 13 Q. Mr. Vickery asked you about clinical trials, 14 randomized controlled clinical trials as looking at 15 the question of efficacy; that is, whether the drug 16 works. Do you recall that? 17 A. Yes, I do. 18 Q. Can you tell the jury, please, with respect to 19 controlled clinical trials that are performed on 20 antidepressant medications, what is the general 21 practice that you're familiar with and that you 22 yourself have utilized in performing controlled 23 clinical trials with antidepressant medications with 24 respect to the gathering of side effect information? 25 A. Well, there's what's called the treatment PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2354 1 emergent side effect listing which you have to fill 2 out, and if you're talking about sponsored trials, 3 that actually surveys a number of different body 4 systems, so you systematically sit down with the 5 patient at prearranged intervals, various per steady 6 weekly intervals or daily intervals, depending on what 7 the design requires, but the treatment emergent side 8 effects asks you to go down and specifically asks, in 9 each organ system, have you had problems, you know, 10 breathing? Have you had problems with palpitations? 11 Have you had problems with headaches? Have you had 12 problems in sexual functioning? Things like that in 13 different areas. 14 Q. And the purpose of that is to elicit from the 15 patient and gather information regarding whether there 16 were any side effects appearing from the drug? 17 A. That's correct. There's also a form that you 18 fill out for spontaneously generated side effects that 19 occur and that that individual either complains about 20 or is noticed by the staff members, so that's in 21 addition. 22 Q. Now, Mr. Vickery also made brief mention of two 23 studies that have come up in the trial already, and I 24 want to ask you one question about them. You're 25 familiar with a study by Dr. Warshaw, Meredith Warshaw PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2355 1 and Martin Keller, entitled, "The Relationship Between 2 Fluoxetine Use and Suicidal Behavior in 654 Subjects 3 with Anxiety Disorders"? 4 A. Yes, I am. 5 Q. The one question I want to ask you is, Mr. 6 Vickery was sort of questioning whether there had been 7 any prospective study, sort of looking forward in time 8 and following patients, on this question of whether 9 there is a true relationship between Prozac and 10 suicide. Is this a paper that follows that 11 prospective design? 12 A. Yes, it is. 13 Q. The paper by Dr. Andrew Leon entitled, 14 "Prospective Study of Fluoxetine Treatment and 15 Suicidal Behavior in Affectively Ill Subjects," 16 you're familiar with that one? 17 A. Yes, I am. 18 Q. That one just came out? 19 A. That's correct. 20 Q. Is that another of the prospective studies, in 21 essence, that follows groups of patients over time to 22 look at the question, among other things, whether 23 there's a true relationship between Prozac and 24 suicide? 25 A. Yes, it is. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2356 1 Q. Now, the last thing I want to ask you about is 2 the Jick article that Mr. Vickery has questioned you 3 about. Do you have a copy of that up there? 4 A. Yes, I do. 5 Q. I want to specifically, if you have it there -- 6 A. Yes. 7 Q. -- turn to Page 217 on which Table 6 appears. 8 A. Yes. 9 Q. Now, Table 6 is the table from which 10 Mr. Vickery has taken the fluoxetine has a 2.1 times 11 the risk of suicide as compared to another 12 antidepressant, that's where that number comes from? 13 A. That's correct. 14 Q. All right. Now, could you tell the jury what 15 is that parenthetical statement that follows that 16 number, 2.1? 17 A. Ninety-five percent confidence interval. 18 Q. All right. And what does that confidence 19 interval show for this 2.1 figure? 20 A. It shows a range of .6 to 7.9. 21 Q. And to a scientist, what does that mean? 22 A. What it means is that any time you include one 23 in the confidence interval, that says that there is no 24 significant difference between that drug and the 25 comparative compound that you've looked at. There's PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2357 1 no difference in relative risk. 2 Q. And what did the authors themselves of the Jick 3 paper conclude about whether there was a significant 4 difference? 5 A. They concluded just what I said, that there was 6 no difference in relative risk amongst all the 7 antidepressants in terms of suicide-associated 8 phenomenon. 9 MR. SEE: Thank you, sir. That's all I have. 10 MR. VICKERY: Your Honor, I have three on 11 redirect, if I may -- I mean, recross. 12 THE COURT: All right. 13 RECROSS-EXAMINATION 14 BY MR. VICKERY: 15 Q. Doctor, just three quick things. Is there a 16 correlation between serotonin syndrome and the blood 17 levels of Prozac, blood concentration levels of 18 Prozac? 19 A. That's an interesting question. I don't know 20 that that's -- I don't know of any data to that 21 effect. 22 Q. Okay. Number two, that book in front of you, 23 the DSM-IV, when was it published? 24 A. It's gone through several. This is the fourth 25 edition, so I think it was '94 or something like that. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2358 1 I'll check. Yeah, 1994. 2 Q. That's a year after the Forsyths' deaths. The 3 DSM-III didn't have those same provisions about 4 akathisia, did it? 5 A. I don't think it had operational definitions 6 for akathisia at all in it. 7 Q. So if Dr. Neal or Dr. Roberts had been told to 8 look for akathisia, and they went to the bible that 9 was in effect in 1993, they wouldn't have found 10 anything to help them diagnose it, would they? 11 MR. SEE: I object to the question. It calls 12 for speculation. 13 THE COURT: Well, he may know whether it does 14 or not. 15 THE WITNESS: Well, I mean, this is how you get 16 a code number. If you're looking about how to 17 diagnose something, it's not a medical textbook. The 18 medical textbook and neurology textbooks at the time 19 did, in fact, define it as a motor and behavioral 20 syndrome, so even in 1992 and '93. 21 Q (By Mr. Vickery) But at least, you will agree 22 with me, that the version of this book -- 23 A. That's correct. 24 Q. -- upon which you base -- 25 A. DSM-III did not have it. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2359 1 Q. Didn't have it. And finally, this Leon article 2 that was written by several Lilly people published 3 last month, you say that's a prospective study? 4 A. It's a prospective encoding of data, yes. 5 Q. Didn't it start collecting data in 1969? 6 A. I forget when they first started. 7 Q. It was like 20 years before Prozac hit the 8 market that they started collecting data on these 9 people; isn't that true, sir? 10 A. I don't recall when they started the data. 11 MR. VICKERY: Okay. Thank you. 12 THE COURT: Anything more, Mr. See? 13 MR. SEE: That's all, Your Honor. Thank you. 14 THE COURT: Thank you. You're excused. And 15 we'll break now for lunch. Please be back at twenty 16 after one. 17 (Whereupon, a lunch recess was taken from 12:20 18 to 1:30 p.m.) 19 THE COURT: Please proceed, Mr. See. 20 MR. SEE: Your Honor, Eli Lilly and Company 21 call as its next witness, Dr. Byron Eliashof. 22 THE CLERK: Please raise your right hand. 23 BYRON A. ELIASHOF, Ph.D., 24 called as a witness on behalf of the Defendant, after 25 having been first duly sworn to tell the truth, the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2360 1 whole truth, and nothing but the truth, was examined 2 and testified as follows: 3 THE CLERK: Please be seated. Please state 4 your name and spell your last name. 5 THE WITNESS: My name is Byron A. Eliashof. My 6 last name is spelled E-L-I-A-S-H-O-F. 7 DIRECT EXAMINATION 8 BY MR. SEE: 9 Q. Good afternoon, Doctor. 10 A. Good afternoon. 11 Q. Tell us, what is your profession? 12 A. I'm a psychiatrist. 13 Q. Okay. And where do you practice psychiatry? 14 A. My office is here in Honolulu on Kapiolani 15 Boulevard, 1441. 16 Q. And can you tell us what kind of psychiatric 17 practice you have? 18 A. At present time, I'm in the general practice of 19 psychiatry. I see people from all ages, from early 20 young adulthood to older folks with a variety of kinds 21 of disorders. Some of them are depressed, some of 22 them are anxious, sometimes they have marital 23 problems, sometimes they have injuries and severe 24 pain. 25 Before this, earlier in my career, I was a PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2361 1 child and adolescent psychiatrist and I also saw the 2 whole spectrum of disorders and problems that you see 3 with kids and children and teenagers. 4 Q. How long have you been a psychiatrist here in 5 Honolulu? 6 A. I've been practicing here since 1967. 7 Q. So that would be 32 years? 8 A. Thirty-two years in practice here in Honolulu. 9 Q. Now, have you always had the private practice 10 or have you practiced in other kinds of situations? 11 A. Well, I've done a variety of things. When I 12 first came here, I was in child and adolescent 13 psychiatry. I was seeing some private patients. I 14 was also working for the State for the Child and 15 Health Services Division. I used to go out to clinics 16 in Waianae and Nanakuli to meet with the various 17 nurses and doctors there if they had any concerns 18 about young children who were having problems. 19 I also was a consultant to the Salvation Army 20 facility for delinquent boys in Kaimuki. I worked for 21 the Department of Education and my work with them 22 involved trying to set up programs to pick up 23 emotional and learning problems in younger children in 24 the first grades, so that they would be able to be 25 helped and get some remediation before they got too PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2362 1 far behind. 2 Q. Let's go back one step. Can you just summarize 3 your education for us, please, starting with college? 4 A. I went to Yale University and I majored in 5 history there. After I left Yale, I went to the 6 Albert Einstein College of Medicine in New York where 7 I took a degree in medicine. 8 Q. Can you tell us what year that was? 9 A. I was there from 1956 to '61. I took an extra 10 year to do some research, and so I spent a fifth year 11 there and then graduated in 1961. 12 Q. After you got your medical degree, you then 13 went on for further training in psychiatry? 14 A. Yes. I went back to Yale where I did an 15 internship in pediatrics. And then after that, I went 16 to Harvard and that's where I studied psychiatry. 17 Q. And how long a program was that? 18 A. That was a three-year program. 19 Q. Did you then become board certified in 20 psychiatry? 21 A. I completed my training. I practiced for 22 several years, which is the requirement to become 23 board certified, and then after I fulfilled the 24 preliminary requirements, I took my boards to become 25 certified in psychiatry. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2363 1 Q. Now, could you tell us, please, in addition to 2 your practice of psychiatry, have you had any role in 3 teaching? 4 A. Yes. I have taught the school of social work 5 at the University of Hawaii. I teach in the medical 6 school and have taught there for many years. I teach 7 third-year medical students about psychiatry and 8 psychiatric illnesses. I also supervise residents in 9 psychiatry and also, as part of my teaching, I was 10 involved in a clinic, it was the Hawaii Mental Health 11 Clinic. We were a group of psychiatrists and 12 psychologists and social workers who provided free 13 services for people who didn't have health insurance 14 and couldn't afford to pay for it and we would 15 sometimes have people in training, who would come 16 through. And so part of my time there, I was on the 17 board of directors to help to organize it. I was 18 seeing people myself and was also supervising people 19 who were treating some of the folks who came through 20 that clinic. 21 Q. That would be the residents as far as their 22 psychiatric training? 23 A. Yes. 24 Q. Dr. Eliashof, is there a professional 25 organization for psychiatrists here in Hawaii? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2364 1 A. Yes, the Hawaii Psychiatric Medical 2 Association. 3 Q. Have you been a member of that group? 4 A. I've been a member of that group since 1967 5 when I first went into practice, and I've held a 6 number of offices. I've been secretary, treasurer, 7 president on two occasions, acted as the legislative 8 representative lobbying in the legislature for 9 improved benefits for mental health and a variety of 10 other tasks. 11 Q. Now, Doctor, let me ask you, you said that part 12 of your teaching role was to both teach medical 13 students and supervise residents in psychiatry? 14 A. That's correct. 15 Q. Do you teach those doctors and psychiatrists in 16 training about Prozac? 17 A. Yes, I did. 18 Q. What did you teach them? 19 A. This is one of the aspects of training is to 20 educate the medical students and much more so the 21 residents, who specialize in psychiatry, about the 22 various medications that are available, and Prozac is 23 a drug that I educate them about so that they'll be 24 familiar with how effective it is, how safe it is 25 compared with the older drugs, for instance, that we PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2365 1 used to have. Part of my training them is to let them 2 know that sometimes there can be some side effects and 3 they have to be aware of that. 4 It's a very effective useful drug that I rely 5 on and that my colleagues in the community rely on, 6 and this is part of the information that I convey to 7 the residents that I'm supervising. 8 Q. Now, Doctor, I've cut some things out of this 9 because we've heard a lot of issues already in the 10 trial, but there are two or three things that are 11 important and I want to ask you about. First of all, 12 as a practicing psychiatrist in this community, were 13 you aware of the case report that was published by a 14 Dr. Martin Teicher in February of 1990 reporting that, 15 in some of his patients, he had given them Prozac and 16 it seemed that they had had suicidal thinking? Were 17 you aware of that article when it came out? 18 A. Yes, I saw it. I remember reading it and -- I 19 was reading it in an airport and was surprised because 20 I had been using this medication, and I had been 21 reading about it in the literature and there was no 22 suggestion that there would be any kind of problem 23 like this, so it caught my attention. 24 Q. Now, when you got this or read this article by 25 Dr. Teicher, this case report, did it cause a change PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2366 1 in the way you prescribed or used Prozac? 2 A. No. Case reports like this are important 3 because they alert us to the fact that some people 4 have had problems. Whether it's due to the drug or 5 not, you just don't know. And my prescribing of 6 medication and prescribing of Prozac has always been 7 guided by the scientific literature, which has done 8 things like double-blind studies, large epidemiologic 9 studies where you have a group of people prescribe the 10 drug and follow them and see what happens, and so it 11 did not change my prescribing practices. 12 If a doctor were to change prescribing 13 practices based on every random case report, the 14 practice of medicine would become chaotic because 15 there are case reports about all kinds of things which 16 are meant to raise our -- just bring things to our 17 attention, but it doesn't mean that they have a 18 scientific basis, and that's what you use for your 19 decision making when you're treating people in your 20 office on a day-to-day basis. 21 Q. Now, Doctor -- 22 MR. SEE: If I may approach the witness, Your 23 Honor? 24 THE COURT: You may. 25 Q (By Mr. See) I'd like to hand you what's PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2367 1 marked as Exhibit 1042, and there's already been 2 testimony in this case that that exhibit is a letter 3 that was sent out by Eli Lilly and Company to every 4 doctor practicing in the United States. And it's 5 dated August 31, 1990. The question I want to ask you 6 is, did you get a copy of that? 7 A. Yes, I did. 8 Q. Now, would you tell the jury, when you got this 9 Dear Doctor letter from Lilly in August of 1990, what 10 was your reaction to it? 11 A. Well, I first read it. And as I got into it, I 12 was very impressed. I thought this was really the 13 height of integrity on the part of a drug company or 14 any kind of company to bring to our attention, I mean, 15 not everyone saw that article that I read, but it 16 brought to every doctor's attention that this report 17 had appeared and it also -- besides informing them -- 18 informing us of the report, also put it in the context 19 of a scientific research that had been done. I 20 thought it was a very responsible kind of thing to do. 21 Q. Now, Dr. Eliashof, on the question whether 22 Lilly provided adequate information and warnings to 23 prescribing physicians as of August of 1990, when the 24 Dear Doctor letter came out, on that question, do you 25 have an opinion whether, in fact, Lilly did provide PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2368 1 adequate warnings to prescribing physicians about this 2 reported risk of suicide that was referenced in the 3 Teicher article? 4 THE COURT: Are you going to qualify him as an 5 expert? 6 MR. SEE: I beg your pardon. I've overlooked 7 that, Your Honor. I do tender Dr. Eliashof as an 8 expert to the Court in the area of general psychiatry. 9 I beg your pardon. 10 MR. VICKERY: I think his qualifications meet 11 the requirements of the rule, Your Honor. 12 THE COURT: The Court finds the witness is 13 qualified to testify in the area of general 14 psychiatry. 15 Q (By Mr. See) Let me ask the question again, 16 Dr. Eliashof. I got step two in front of step one. 17 On the question whether Lilly, in sending out the Dear 18 Doctor letter that you've talked about, in August of 19 1990, do you have an opinion whether Lilly provided 20 adequate warning to prescribing doctors like yourself 21 on this question of the issue of a risk of suicide 22 that was reported in the Teicher article? 23 A. Yes, I do. 24 Q. Okay. Would you tell us what your opinion is? 25 A. They did provide adequate warning. They PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2369 1 brought up this case that had been reported by 2 Dr. Teicher, and they then went on to talk about the 3 various studies that have been done on the drug, and 4 most importantly, they reminded all of the doctors 5 that when you're treating someone with depression, 6 suicide is always a potential risk. It's part and 7 parcel of one of the symptoms of depression, that it's 8 one of the things that can appear at depression at any 9 time. Sometimes you can foresee it and many times, 10 you can't, and that was emphasized in this letter. 11 Q. Now, Doctor, the other area that I want to get 12 into with you has to do with testimony that was given 13 earlier in this trial by Dr. David Healy. Among other 14 things, Dr. Healy told the jury that patients who had 15 mild to moderate versions of major depression were 16 less likely to attempt or commit suicide than people 17 who did not have major depression. And the question 18 that I want to ask you is, would you tell the jury 19 your view on that topic? 20 A. There is absolutely no scientific foundation 21 for that statement. I've read thousands of articles 22 since I've been in medical school. I've read, I don't 23 know how many, textbooks. I've been to hundreds of 24 conferences and lectures and suicidal thinking is 25 always, always listed as either one or two of the PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2370 1 highest markers as a risk for suicide. I mean, it 2 just stands -- it appears everywhere. Nowhere has 3 that ever been disagreed with except this other doctor 4 who said that. 5 And I mean, if you stop and think about it, if 6 someone in your family came to you and said, I'm 7 feeling terrible, I can't stand going on, and I keep 8 thinking of suicide, would you tell them, oh, that 9 means you're probably not going to do it, so don't 10 worry about it, or would you tell them, just go right 11 on thinking about it because that's going to protect 12 you from committing suicide? I mean, it just goes 13 against all common sense as well as a whole body of 14 scientific literature that goes back since I first 15 started reading this material back in medical school 16 in 1961. 17 Q. Now, another thing that Dr. Healy told the jury 18 was that a person who had suicidal thinking was 19 actually inoculated against committing suicide. Would 20 you tell the jury what your opinion is about that? 21 A. There is absolutely no scientific foundation 22 for that anywhere that I've seen in the literature. 23 And again, I've read thousands of articles, dozens of 24 textbooks, gone to many, many lectures and courses. 25 It does not inoculate you against committing suicide. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2371 1 Just the opposite, it raises the possibility and the 2 likelihood that you will commit suicide. It just 3 stands to reason. 4 Q. Dr. Eliashof, finally, in your 30-some-odd 5 years in practicing psychiatry here in Honolulu, and 6 your involvement with the professional organization of 7 psychiatrists here, have you become familiar with the 8 accepted and prevailing viewpoint of the medical and 9 psychiatric community in Hawaii regarding the use of 10 Prozac to treat major depression? 11 A. Yes. 12 Q. Would you tell the jury what that is? 13 A. I've been an active member of the psychiatric 14 societies since 1967 when I went into practice. I go 15 to conferences, we take courses together, we go to 16 lectures, and we're constantly in discussion about 17 various problems that come up, various issues, the 18 medications we're using, maybe modifications of things 19 we're using so that they will be more effective and 20 Prozac is -- it is recognized and accepted as an 21 effective and a safe drug for treating depression. 22 MR. SEE: Thank you, sir. I pass the witness. 23 THE COURT: Mr. Vickery. 24 MR. VICKERY: Thank you, Your Honor. 25 CROSS-EXAMINATION PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2372 1 BY MR. VICKERY: 2 Q. Good afternoon, Doctor. 3 A. Good afternoon. 4 Q. My name is Andy Vickery and I met you briefly 5 at the lunch hour. A few questions. First of all, I 6 have a housekeeping matter. Are you actively involved 7 in practice now? 8 A. Yes, I am. 9 Q. And are you also actively involved in 10 litigation matters, testifying in lawsuits? 11 A. I don't do very much testifying, but I do a lot 12 of evaluations. 13 Q. Okay, sir. You had given us a list with your 14 report back in '97 of about 20 cases in the four years 15 preceding that? 16 A. Yes. 17 Q. Is that about what it runs, about five a year? 18 A. This past year, I think was one, but that's 19 probably a fairly good average. 20 Q. And the other one case that you listed in the 21 report in which you worked for Mr. Burke's -- actually 22 for Ms. Aburano sitting back here, have you had other 23 occasions to do work either for that firm, for 24 Mr. See's firm, or for Eli Lilly? 25 A. No. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2373 1 Q. Tell us, if you would, your rate for 2 professional services as a witness. 3 A. I charge $350 an hour for time spent in 4 preparation, and I charge $600 an hour for time spent 5 testifying or in deposition. 6 Q. Okay, sir. And can you give us an idea of how 7 many hours, to date, you have gotten involved on this 8 issue? 9 A. I would estimate that it's been about 50 hours. 10 Q. At the $600 an hour rate or at the other rate? 11 A. At the lower rate, the $350 rate. 12 Q. Now, today I guess is a full day at the $600 an 13 hour rate? 14 A. No, depending on how many hours you keep me 15 here, a couple of hours. 16 Q. I promised you out in the hall I'd get you out 17 quick, didn't I, so I will. I live up to my promises. 18 Okay. So if it's 50 hours at the 350 rate, 19 that's between 15 and $20,000, something like that? 20 A. Yes. 21 Q. In your report, you said that you have had good 22 success yourself in giving Prozac? 23 A. Yes. 24 Q. And that you have seen very rapid, favorable 25 responses in patients you've given it to, right? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2374 1 A. That's correct. 2 Q. How rapid? 3 A. Within a couple weeks. 4 Q. Have you ever seen them in a couple of days? 5 A. Oh, I've seen people who came back a few days 6 later and said they felt much better. I don't think 7 that was due to Prozac. I think it was because they 8 had seen someone who they were able to unburden their 9 problems to and who they felt would be able to help 10 them and who took an interest in them. I don't think 11 that Prozac clears up depression in a couple days. 12 Q. Tell me this, when you teach residents about 13 Prozac and other drugs, what do you tell them about 14 the importance of studying the package insert and 15 learning what the drug company knows about it? 16 A. One of the points that I make is that they need 17 to be familiar with Prozac, not just with its use for 18 depression, but they need to -- not read the package 19 insert, but that's just where their information about 20 the drug begins. They need to read the general 21 medical literature because there's much more to learn 22 about it, talking to other clinicians who have used 23 it, reading articles, going to lectures and, of 24 course, reading the package insert, because the 25 package insert tells you things like what the proper PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2375 1 doses are, how it might interact with other drugs, 2 what kinds of side effects you should look for, what 3 kinds of precautions you should take in case they're 4 on other medications, there are warnings. There's a 5 whole body of information in there that provides you 6 with kind of a skeleton of what you need to know to be 7 able to safely prescribe the drug, and then you need 8 to supplement that with other kinds of information. 9 Q. In your report, Dr. Eliashof, you say, quote, 10 the drug insert provided by the manufacturer for 11 Prozac is comprehensive and provides safe and 12 effective guidelines for the use of the drug. Now, 13 that seems to be a little at odds with what you're 14 saying here. Is the package insert comprehensive or 15 do you have to go outside of what the drug company 16 tells you in the package insert to safely administer 17 these drugs? 18 A. The package insert in itself is comprehensive 19 enough to be able to use the drug and use it safely, 20 but there are things -- for instance, when the drug 21 first came out, sometimes you would prescribe the 22 usual 20-milligram capsule dose and someone would have 23 some side effects, and you would want to reduce that 24 dose. 25 So one of the things that I read someplace, or PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2376 1 maybe heard about it from one of my associates, was 2 that Prozac dissolves in water, and if you have the 3 patient open the capsule and put it in water and take 4 half a cup one day and half the cup the next, that's a 5 way of getting them started on lower doses. That 6 didn't appear in the drug insert, but it was helpful 7 information. But in terms of answering your question, 8 the information that is contained in the package 9 insert is sufficiently comprehensive to be able to 10 prescribe it safely. 11 Q. Do you teach your residents that there are 12 different sections of the package insert, like there's 13 a warning section and there's a precaution section and 14 there's an events associated temporally section? Do 15 you teach them about that? 16 A. I teach them about the overall content. I 17 don't teach them in terms of, now you need to look at 18 the precaution section and you need to look at the 19 warning section. I teach them about the content of 20 the insert, and I encourage them to read further about 21 it. 22 Q. Okay. Now, you have given testimony here today 23 that this package insert -- and it's in evidence, by 24 the way, as Plaintiffs' Exhibit 2, the one that was in 25 effect at that time. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2377 1 A. Yes. 2 Q. -- is adequate to fully inform the prescribing 3 doctors of any dangers that might be associated with 4 Prozac. Is that your opinion? 5 A. Yes. 6 MR. VICKERY: May I approach the witness, Your 7 Honor? 8 THE COURT: You may. 9 Q (By Mr. Vickery) I'm going to hand you a 10 copy, and this is just an extra copy here, and what I 11 have done, Doctor, is I have, on Page 2, highlighted 12 with a yellow highlighter the warning section. What 13 I'd like for you to do, if you would, is find those 14 warnings that Mr. See was asking you about that deal 15 with akathisia or suicide or any of the kind of things 16 that you think they have given proper warnings about, 17 and highlight them in that document for me. 18 A. I believe in this earlier version of the drug 19 insert, I don't believe there is a reference to 20 akathisia. I'll have to read this. Do you have a 21 larger copy? I'm having trouble reading this. 22 Q. I know. That's a problem for the prescribing 23 physicians, too, isn't it, sir? 24 A. Not if they have time. 25 Q. Okay. Well, take your time because you've just PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2378 1 sworn that this is an adequate warning, so take your 2 time, if you would, and just highlight for us in 3 yellow where the warnings are about this problem. 4 A. There's no reference in this section to 5 suicide. 6 Q. Is there a reference to akathisia? 7 A. No, there is not. 8 Q. So at least in the warning's section of the 9 package insert, there is nothing about either of those 10 two things at the time this drug was prescribed for 11 Mr. and Mrs. Forsyth; is that true? 12 A. Yes. 13 Q. Okay, sir. Now, you have testified, just a few 14 minutes ago, that this package insert contains some 15 warnings somewhere that fully apprise prescribing 16 physicians of the dangers of akathisia or suicide, so 17 all I'm asking you to do is to find the language in 18 there upon which you base your opinion that it's fully 19 apprising them. 20 A. Well, on the subject of suicide -- 21 Q. Excuse me, Doctor, I think you're about to say 22 something non-responsive. Can you find the language 23 in the warning? Can you find it in the package 24 insert? 25 A. What I'm about to say is that the package PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2379 1 insert is adequate for prescribing. It does not 2 mention suicide because suicide is not a risk of using 3 Prozac. 4 THE COURT: Mr. Vickery wants you to read 5 through the rest of the insert. 6 THE WITNESS: Well, I don't see a place to -- 7 where akathisia or suicide is mentioned to highlight. 8 Q (By Mr. Vickery) Let's see if I can help you. 9 May I? I have now highlighted for you the precaution 10 section. Is that different from the warning section? 11 A. Yes. 12 Q. And I highlighted for you what Eli Lilly had to 13 say about suicide in the precaution section. Would 14 you just read that for me? 15 A. You know the copy you've given me is blurred 16 and it's not as crisp in terms of the legibility. 17 Q. I'll give you the best copy we have. 18 A. So if you have one that's clearer, I'd 19 appreciate that. I also misunderstood your question. 20 I thought you were referring just to the warning 21 section, not to the insert as a whole. 22 Q. Which question did you misunderstand? 23 A. I thought you were directing me to whether they 24 had said anything in the warning's section about 25 suicide or akathisia, and I read that and I didn't see PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2380 1 it. I didn't realize that you were referring to the 2 insert as a whole. 3 Q. Now that you realize I'm referring to that, you 4 see something that's not a warning, but it's a 5 precaution, don't you? 6 A. Yes. 7 Q. And what I've given you is a straight Xerox 8 copy because the size print in that is the size print 9 that the package insert comes, isn't it? 10 A. It's not as clear as the print in the package 11 insert because I read package inserts all the time. I 12 don't have this much difficulty making them out. 13 Q. Okay. 14 A. Do you have a package insert? 15 Q. No, sir, I don't. I just have the Xerox copy 16 that was provided to me. 17 A. Well, it's not the greatest. Let me see if I 18 can go on to the next part. 19 Q. If you would just read out loud what they say 20 about suicide. 21 A. "Suicide, the possibility of a suicide attempt 22 is inherent in depression and may persist until 23 significant remissions occur. Close supervision of 24 high-risk patients should accompany initial drug 25 therapy. Prescriptions for Prozac should be written PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2381 1 for the smallest quantity of capsules consistent with 2 good patient management in order to reduce the risk of 3 overdose." 4 Q. Now, that doesn't say anything about Prozac 5 causing either akathisia or suicide for some patients, 6 does it? 7 A. That's correct. 8 Q. And, in fact, when it talks about overdose or 9 prescriptions written for small numbers, the bells 10 that go off in your head are overdose bells, don't 11 they? 12 A. Yes. Well, that's part of it. Also, the 13 reminder that suicide is inherent in depression. 14 Q. Which, of course, you knew as a psychiatrist 15 anyway? 16 A. I think anyone who has training in medicine, we 17 all take courses in psychiatry, and since depression 18 is the most dangerous psychiatric illness, everyone is 19 taught that suicide is a risk or danger as part of 20 depression. 21 Q. Dr. Eliashof, are you able to point in that 22 document, sir, in the entire document, anywhere in 23 that document to where there's some warning about 24 akathisia? 25 A. Did you highlight it for me? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2382 1 Q. No, sir, I didn't do that one for me because 2 I'm not the one that swore that it was adequate. You 3 are. 4 MR. SEE: Your Honor, I object to Mr. Vickery's 5 comment and I move that it be stricken. 6 THE COURT: Sustained. 7 THE WITNESS: I don't remember from memory 8 whether there's a reference to akathisia in here or 9 not, and I really am having a hard time reading this 10 because it's a Xerox, but it's a blurry one and it's 11 hard to read and to sit here -- 12 THE COURT: Do we have another exhibit that's 13 clearer? 14 MR. VICKERY: Your Honor, I think I gave him 15 the best copy I have. 16 MR. SEE: Dr. Eliashof, if you look at the Dear 17 Doctor letter -- 18 THE WITNESS: Yes. 19 MR. SEE: -- it has a copy of the prescribing 20 information attached to it. It's probably easier to 21 read. 22 THE WITNESS: Yes, this is much more readable. 23 Q (By Mr. Vickery) Is it in the same size 24 print? 25 A. No, it's larger print. It is also a Xerox, but PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2383 1 the letters aren't smeared. 2 Q. Well, use the Dear Doctor letter, if you would, 3 as your guide and find the place in the small print -- 4 MR. VICKERY: I'm sorry, Your Honor, is it okay 5 to approach the witness? 6 THE COURT: You may. 7 Q (By Mr. Vickery) Find the place in the small 8 print where it mentions akathisia and highlight it for 9 us, please. 10 A. Akathisia is referred to in -- there's a 11 section in the package insert which is called, "Other 12 events observed during the premarketing evaluation of 13 Prozac." 14 Q. Okay. Now -- 15 A. And this doesn't mean that it's been caused by 16 Prozac, but it has been observed in the process of 17 testing the drug, and akathisia is one of the findings 18 that is mentioned in this package insert. 19 Q. Thank you, sir. Now, would you use that larger 20 print version as your guide to find it on the package 21 insert, the smaller print one that you've testified is 22 satisfactory and legally adequate? 23 A. Would you repeat that, please? 24 Q. Would you, please, just use the larger version 25 now that that's helped you find -- use that as your PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2384 1 guide to find it and highlight it on the smaller 2 version, the small-print version. 3 Thank you, sir. Is there anything, in either 4 version, warning doctors that Prozac can cause 5 akathisia, suicidality, or homicidality? 6 A. It doesn't cause that. Why would you give a 7 warning that Prozac can cause suicidality, 8 homicidality, or akathisia when there's no scientific 9 evidence that it does that? 10 Q. Well, that's what we've been fighting about 11 here the last two or three weeks, whether it does 12 cause it or not. You agree with me that there's 13 nothing in the warning that this drug can cause any of 14 those, don't you? 15 A. It also doesn't say it can cause measles. That 16 has nothing to do with it. I mean, it doesn't seem to 17 me that in preparing a package insert, you're going to 18 list all the things it doesn't cause. It makes no 19 sense at all. What you talk about are the things that 20 it can cause, like some of the interactions with drugs 21 that are mentioned here or some of the other things 22 that have been observed. 23 Q. Well, let me ask you this: We heard testimony 24 earlier today from a witness called by Eli Lilly that 25 said it can cause akathisia. Do you agree with him or PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2385 1 disagree with him? 2 A. I disagree with him. 3 Q. Okay. So he was wrong if he said that? In any 4 event, you agree -- 5 A. We have a difference of opinion. 6 Q. Okay. That's fine. 7 A. From my point of view, although it's been 8 reported, there is no scientific evidence in tens of 9 thousands of patients who have been investigated for 10 this. There was one study that was recently 11 published -- 12 Q. Excuse me, Doctor. I don't know what question 13 you're answering. If you would just please confine 14 yourself -- 15 A. I guess I'm responding to what seems like a 16 misleading question. 17 Q. I don't mean to mislead you. I don't think I 18 asked you anything about that. I'm trying to confine 19 my questions to the scope of what Mr. See asked you on 20 direct. That's what I'm obliged to do here. 21 MR. VICKERY: Your Honor, may I publish the 22 copy that the doctor has highlighted to the jury? 23 THE COURT: You may. 24 MR. VICKERY: Thank you. 25 Q. Now, I was interested in your testimony about PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2386 1 the Teicher article not changing the way doctors 2 prescribe things. What does it take in order to 3 change the way that doctors -- to change the 4 prescribing practices of doctors of a psychoactive 5 drug like Prozac? 6 MR. SEE: I object to the question, that it's 7 based on a premise and it's inconsistent with what the 8 doctor just testified to. He testified about what 9 changed or didn't change the way he prescribed. 10 Q (By Mr. Vickery) Okay. Let me be specific to 11 you, then. What would it take for you to change the 12 way that you prescribe this medication? 13 A. I would need to see a scientific study that 14 showed that Prozac caused suicidality or caused some 15 kinds of problems that I felt were incompatible with 16 safe prescribing. 17 Q. What about this Dear Doctor letter you've been 18 given, Exhibit 1042? Come straight from the drug 19 company to you. If, in that letter, instead of 20 reassuring you that Prozac doesn't cause this, if they 21 had said, look, in a small percentage of people, our 22 drug may cause akathisia which may lead to violence or 23 suicide, if the drug company itself had told you that, 24 would that influence the way that you prescribe this 25 medication? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2387 1 A. Well, that assumes that -- it seems to me that 2 that assumes that there's been some indication that 3 Prozac causes akathisia and suicide, and there's no 4 evidence for that. If that letter had said, you know, 5 we found some studies that have been scientifically 6 pursued and here are the references, if you want to 7 look at it, and we now feel that this is a potential 8 side effect that you need to be aware of, depending on 9 the frequency and depending on the patient, it might 10 or it might not alter how I would use the drug or not. 11 Q. You would certainly take what the drug company 12 itself told you, either in a Dear Doctor letter, in 13 the package insert, or in a visit from a salesperson, 14 you would certainly take that into account and heed 15 what they said to you, wouldn't you? 16 A. I would heed it and I would assume that it was 17 based on scientific evidence and not anecdotes. 18 Q. Okay. Now, you described that letter as the 19 height of integrity. Can you explain for us why that 20 letter came out on August the 31st, 1990, if, as the 21 evidence I will represent to you, shows that Eli Lilly 22 knew about that article in January of 1990? 23 MR. SEE: Objection, irrelevant to this case. 24 THE COURT: Sustained. 25 Q (By Mr. Vickery) Let me just ask you this: PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2388 1 Do you think it's the height of integrity for a drug 2 company to tell their drug reps, do not initiate 3 discussions of this article with Dr. Eliashof and the 4 other folks in Hawaii? 5 MR. SEE: Objection, irrelevant to this case. 6 THE COURT: I'll allow the question, but you're 7 going to have to develop it. 8 MR. VICKERY: I will, Your Honor. 9 THE COURT: Rephrase it. 10 Q (By Mr. Vickery) Is it the height of 11 integrity for the drug company to say, as I represent 12 to you that they did, in January and February of 1990, 13 this new article is out, but don't tell the doctors, 14 do not initiate discussions with the doctors about 15 this because it's not part of our marketing strategy. 16 Is that the height of integrity? 17 A. Well, there are two parts to that. From my 18 point of view, there are two aspects to that question 19 because one of the things that, for me, as a 20 practicing clinician, that has been very upsetting, is 21 the negative publicity that Prozac has gotten partly 22 as a result of this article, and as a result, people 23 who I have seen, who could have been helped with their 24 depression, have been frightened and not wanting to 25 take it because of this kind of anecdotal information. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2389 1 From my point of view, the adverse publicity 2 has harmed many people, and for the drug company not 3 to promote information about an article that might 4 frighten people unnecessarily, until they prepare a 5 responsibility statement of their own, to me is not 6 irresponsible. 7 Q. So you think that taking seven or eight months 8 to prepare a response is the integrity -- that's the 9 proper thing to do? 10 MR. SEE: Objection, irrelevant. 11 THE COURT: We are getting afield here, 12 Mr. Vickery? 13 Q (By Mr. Vickery) Okay. The letter that was 14 sent to you in August of 1990, the tone of that letter 15 was to reassure you, just as it did in way back toward 16 the end of the package insert, that Eli Lilly does not 17 believe that this drug causes these problems; isn't 18 that true? 19 A. Yes. 20 Q. Okay. Now, finally, you gave a couple of 21 opinions about suicide attempts and suicidal thinking. 22 Those were not things that were contained in your 23 initial report, were they? 24 A. I'm not sure what you're referring to. Could 25 you clarify that? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2390 1 Q. Mr. See asked you at the end about whether a 2 suicide attempt would actually inoculate people, and 3 he asked you whether suicidal thinking or suicidal 4 ideation was a high marker for suicide. Remember 5 that? 6 A. I don't think that was the second question. 7 Q. Okay. What was the second question? 8 A. I thought his first question had to do with 9 suicidal thinking. Someone had said it inoculates 10 people against committing suicide, and I'm not clear 11 on the second one. Would you repeat that? 12 Q. I think one of them was whether suicidal 13 thinking was a predictor of suicidal acts. 14 A. Yes. 15 Q. And you said, yes, it is? 16 A. That's correct. 17 Q. And the second one was whether suicidal 18 attempts actually had a protective effect, and you 19 said no? 20 A. No. Suicidal thoughts have a protective 21 effect, that was the question. 22 Q. Okay. 23 A. Suicidal thoughts have the opposite of a 24 protective effect. They make it more likely that a 25 patient will commit suicide than if they don't have PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2391 1 suicidal thoughts. 2 Q. Okay, sir. My question really goes to the fact 3 that these two opinions, that Mr. See asked you to 4 give here, were things that were not contained in your 5 written report. They were things that he asked you to 6 opine about in response to the evidence we've heard; 7 is that true? 8 A. Yes. I've never heard such a statement in all 9 my years -- you know, 30 some years of practice. It 10 wouldn't have occurred to me to make any comment like 11 that until I heard about it today. 12 Q. I don't mean to be critical. I'm not being 13 critical of you at all about it, sir. If you take 14 what I said that way, please accept my apology. I 15 just wanted to establish that that was something that 16 was not in your report, that you were asked to give in 17 court, true? 18 A. True. 19 Q. Now, are you a suicidologist? 20 A. You mean a -- someone who specializes in 21 suicidology? 22 Q. Yes sir. 23 A. No, I am not. 24 Q. And can you tell us, what is the incidence 25 rates per year for suicide in the mild to moderate PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2392 1 depression? I'm not talking about prevalence. I'm 2 talking about incidence. Do you understand the 3 difference between those two? 4 A. The frequency with which it occurs. 5 Q. Okay. And can you tell me, what's the 6 incidence rate per year for suicide in the population 7 of people who have mild to moderate depression? 8 A. No. I'm aware that there are differences 9 depending on which study you read, and one of the 10 commonly accepted statistics is that the rate is 25 11 times greater in depressed patients as a whole than in 12 the average general population. But to break it down 13 further into seriously depressed, moderately, or 14 mildly depressed, I don't know the differences in the 15 statistics. 16 Q. All right, sir. Finally, when you were 17 studying at Harvard, did you meet or study under 18 either Martin Teicher or Jonathan Cole? 19 A. No. 20 Q. Do you know who Jonathan Cole is? 21 A. Yes. 22 Q. Is he senior to you? 23 A. Yes. 24 Q. And is he a fairly renowned 25 psychopharmacologist? PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2393 1 A. He is highly respected and very well-known. 2 Q. Does the fact that his name appears as 3 co-author on the article in 1990 with Dr. Teicher 4 cause you to give what they are saying a little more 5 credibility? 6 A. It caused me to pay more attention to it than I 7 would have otherwise. It didn't make me feel that it 8 was a scientifically conducted study. 9 MR. VICKERY: Okay. Dr. Eliashof, thank you 10 very much. I pass the witness. 11 MR. SEE: Nothing further, Your Honor. Thank 12 you, Doctor. 13 THE COURT: Thank you. You're excused. 14 MR. SEE: Your Honor, at this time, we would 15 read the excerpted portions of the deposition of 16 Dr. Richard Hawley. 17 THE COURT: Very well. 18 MR. SEE: Your Honor, if I may, Mr. Burke will 19 take the stand and read the portion of the testimony 20 of Dr. Hawley. 21 THE COURT: This has been designated? 22 MR. SEE: Yes, sir. 23 THE COURT: Do you want the reporter to take 24 this down or not? 25 MR. SEE: It really doesn't matter, so I don't PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2394 1 think it is necessary. The designations are in the 2 record. 3 THE COURT: You agree with that, Mr. Vickery? 4 MR. VICKERY: Yes, I do, Your Honor. There was 5 just a couple -- there were a couple of areas where we 6 had asked that additional portions be read. Counsel 7 assures me they're going to do it. We have no 8 objection to this procedure or to the fact that we 9 give Mrs. Stuhr a break. She doesn't need to take 10 this down. 11 THE COURT: All right. We'll give her a break. 12 MR. SEE: Your Honor, during the reading of 13 Dr. Hawley's deposition, I would put up before the 14 jury Exhibit 1011, which is a blowup of the 15 translation of Dr. Hawley's chart. 16 (Whereupon, Dr. Hawley's deposition testimony 17 was read.) 18 MR. SEE: Your Honor, that concludes the 19 reading of the deposition of Dr. Richard Hawley. 20 THE COURT: You have one more? 21 MR. SEE: We do. We have one more to read. 22 THE COURT: Let's take a break now. Please be 23 back at three. I want to meet with counsel. 24 (Whereupon, the following proceedings were had 25 in open court out of the presence of the jury.) PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2395 1 THE COURT: I think we should take up at this 2 time the objections that Lilly has raised with respect 3 to plaintiffs' rebuttal witnesses. 4 MR. VICKERY: Very well. 5 THE COURT: So I guess we'll be getting to that 6 juncture in the next few minutes. 7 MR. VICKERY: We could get to that in the next 8 few minutes. I don't know how long it's going to take 9 them to read the Celestine Starr testimony, but we can 10 do it in the next few minutes or first thing in the 11 morning for certain. Do you want me to address them 12 further, Your Honor? 13 THE COURT: Well, I've read through Lilly's 14 memorandum here. 15 MR. VICKERY: Well, I have, too. It was given 16 to me this morning, and I didn't have a chance to 17 respond anything in writing, but I would just say this 18 about the three, Your Honor -- 19 THE COURT: Are you prepared to argue this now 20 or not? 21 MR. VICKERY: Yes, I can argue it now. 22 THE COURT: All right. 23 MR. VICKERY: First of all, with respect to 24 what the law is, the best thing that I can find, Your 25 Honor, unfortunately is unpublished, and like Mr. See PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2396 1 did earlier, I'll simply seek guidance. It's one of 2 those crazy cases that has a citation so you can find 3 it. The citation is 869 Fed 2nd 1497, but then it 4 says it's an unpublished disposition, but it deals 5 with a question of surprise witnesses and specifically 6 with the requirements under Hawaii local Rule 235-7. 7 And it says that, quote, Listing of witnesses in 8 pretrial filings is not required under Rule 16, but 9 it's required under Hawaii local Rule 235-7 with the 10 exception of impeachment or rebuttal witnesses. 11 And then on the next page it says, "Rebuttal 12 evidence is evidence introduced by a plaintiff to meet 13 new facts brought out in a defendant's case in chief." 14 Now, we've got three bits of evidence here. Number 15 one is Dr. Hoepfel. Lilly's position is we shouldn't 16 be able to call her because we didn't list her. Well, 17 the reason I'm calling her is to respond to things 18 that Lilly brought out in the course of the trial. I 19 couldn't possibly have foreseen that they were going 20 to do that. These were things that Mr. See 21 specifically told the Court was his work product. So 22 I couldn't very well say, I think he might pull an 23 epidemiological study out of his briefcase, Your 24 Honor, and so therefore, if he does do that, I'll have 25 an epidemiologist to talk about -- PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2397 1 THE COURT: That might be an educated guess. 2 MR. VICKERY: Well, Mr. See is very industrious 3 and I can't always predict what he's going to do. 4 Certainly I didn't know in this instance, Your Honor. 5 So we're talking about a short witness who has 6 specific expertise to address a matter that they have 7 placed considerable emphasis on and about which we had 8 no advance warning. 9 The second is Dr. Beasley. As I said 10 yesterday, Dr. Beasley is a Lilly employee. It had 11 been my hope and my expectation that I would simply 12 get to cross-examine Dr. Beasley. He was on my 13 witness list, but I didn't make deposition 14 designations because I had hoped to cross-examine him. 15 However, the testimony that we have marked, which I 16 provided the Court and which will take about 25 17 minutes to read, is directly responsive to the 18 testimony of Dr. Tollefson. So it is rebuttal 19 testimony. 20 Lilly seems to have the notion that rebuttal 21 testimony is something that can't be foreseen or 22 anticipated. What this case that I just cited for 23 you, which is -- by the way, the style is Goldfinger 24 Hawaii versus Polynesian Resources, Inc. What it 25 points out is that, no, rebuttal testimony is not PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2398 1 evidence that's a surprise. It's evidence that's in 2 response to the defense's case. So were it otherwise, 3 I'm sure you can think of the implications for the way 4 the Court would have to manage its docket if every 5 plaintiff had to say, well, the defendant might bring 6 this bit of evidence as part of their defense, and so 7 I need to rebut their defense in my case in chief, 8 then rebuttal would have no meaning whatsoever. 9 So that's why I would ask the Court, most 10 earnestly, to allow us to read that 25 page -- or 25 11 minutes from Dr. Beasley. 12 And finally, there is Dr. Ron Maris. The Court 13 has already ruled that he is a proper witness in 14 rebuttal. Lilly's position seems to be -- this one is 15 diametrically opposite -- 16 THE COURT: My ruling was specifically that he 17 was subject to the order on rebuttal. 18 MR. VICKERY: I understand exactly what your 19 ruling was, Your Honor. And that's why I'm going to 20 call him is to respond to things that Lilly has 21 brought out in its case in chief. That's one of the 22 reasons, Your Honor, anticipating this discussion that 23 I brought out with Dr. Eliashof just a few minutes ago 24 that he was asked two suicide opinions by Mr. See 25 which weren't even in his report. He asked them in PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2399 1 response to what's gone on in the case, but there are 2 two opinions that I would expect Dr. Maris to address. 3 So it's not fair for Lilly to say, well, we can 4 go beyond the scope of our expert's report and ask 5 someone about suicide matters and we can say that it's 6 the depression that caused this and it would have 7 happened anyway, that's our theme in our case in 8 chief, but the plaintiffs can't respond to it, and 9 that's why I want to call Dr. Maris. 10 THE COURT: Do you have a copy of that 11 Goldfinger case? 12 MR. VICKERY: Yes, I do, Your Honor. It's got 13 our writings on it, but I'd be glad to tender it to 14 Mr. Scarborough. 15 MR. SEE: Is there a copy for counsel? 16 MR. VICKERY: Unfortunately, that's the only 17 copy I have. 18 THE COURT: Well, I'm glad that I was affirmed, 19 anyway. 20 MR. VICKERY: I thought you might like that, 21 Your Honor. And the other thing that -- 22 THE COURT: I give you two points for that. 23 MR. VICKERY: Thank you, Judge. Westmates are 24 wonderful because you can say, give me something that 25 the judge has been involved with. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2400 1 235-7, Subparagraph I, Your Honor, of the local 2 rules requires a listing of all witnesses likely to be 3 called at trial, quote, except for impeachment or 4 rebuttal. So when they say, well, gosh, you haven't 5 complied with the docketing order and the local rules 6 and all of that, we rest on the verbiage of the rule 7 itself. 8 THE COURT: 235-7. 9 MR. VICKERY: Subparagraph I. 10 THE COURT: 235-7. 11 MR. VICKERY: Yes, Your Honor, 235-7 12 Subparagraph I. Ms. Mangrum just pointed out to me 13 that I may have cited the '97 number, Your Honor. 14 THE COURT: I think it would be -- it would be 15 more like 51 or so. 16 MR. VICKERY: I think she's right. You all 17 changed your numbers on us and I had my book here and 18 I should have given the Court the right number and it 19 would take me a few minutes to dig up the right one. 20 THE COURT: Well, Mr. See, you want time to 21 read this case or -- 22 MR. SEE: I wouldn't mind seeing it to tell you 23 the truth, but, you know, I'm ready to speak to the 24 issues if it's the Court's convenience to hear them. 25 And I'd like to talk to Dr. Hoepfel and Dr. Maris and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2401 1 let Ms. Mangrum talk to Dr. Beasley, if possible. 2 On Dr. Hoepfel, I would just say this, the 3 Court's scheduling order directed us how to proceed 4 regarding expert testimony, and we were directed for 5 the plaintiffs to disclose and then for the defendants 6 to disclose, and then after a time, the plaintiffs 7 could disclose rebuttal experts. 8 And I would submit this, the spirit of that 9 rule, the spirit of that kind of a schedule is if the 10 plaintiff discloses an internist and a cardiologist, 11 and then I turn around and disclose, well, I've got a 12 pathologist, injecting a new area of expertise, a new 13 issue in the case, I found something in the blood, 14 then they ought to go out and get a pathologist. 15 That's what a rebuttal expert is for. 16 We have a very interesting history here with 17 respect to Dr. Maris. Plaintiff discloses experts, a 18 bunch of them, and we've litigated about a bunch of 19 them, and then we disclosed experts, and then the 20 plaintiffs disclosed several rebuttal experts, 21 including Dr. Maris, and so I went and took his 22 deposition. And what do I discover, but that 23 Dr. Maris had written his report in full before the 24 plaintiffs' first disclosure date. 25 He had been retained, formed his opinion, PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2402 1 written his report, and there it was, but he had been 2 told, oh, well, we're not going to disclose you right 3 now. Maybe a little later. And so they held that 4 report by this so-called rebuttal expert already 5 written, opinion already formed, until we had 6 disclosed and only then, oh, here's Ron Maris. He's 7 in rebuttal to your experts, and with respect, that's 8 just impossible. 9 Dr. Maris wrote his report before he ever knew 10 who our experts were. There's a word for that, and I 11 think the word is sandbag, and it's not how the system 12 was expected to operate in fairness of when the 13 plaintiff ought to have an opportunity for some new 14 area to have a rebuttal expert. 15 What's presented now is here is Dr. Hoepfel 16 who's been sitting out in the gallery there for many 17 days. I have never seen a report from her. I've 18 never been able to depose her. I've never spoken to 19 the lady. I haven't the vaguest idea what she's going 20 to say and yet, Mr. Vickery proposes that now at this 21 stage in trial, he be permitted to put on that expert 22 and let her testify to the jury. How in the world 23 would I cross-examine that doctor? I have no idea 24 what she's going to say and here we've been in trial 25 for weeks. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2403 1 Number one, it is absolutely, absolutely the 2 most unfair, most unjust thing I've ever seen in 20 3 years trying cases. I've never seen this in my 4 career, that the plaintiff would show up on the last 5 day of trial and say, oh, I've got another expert and 6 I want to put her on. 7 There was time to disclose rebuttal experts, 8 they didn't do it with Dr. Hoepfel. This business 9 about -- Mr. Vickery said several times that I pulled 10 epidemiology studies out of my briefcase, and that he 11 was amazed that such issues would arise. Well, the 12 Court will recall we've been litigating over an 13 epidemiology study low these past couple of years, the 14 Jick study. Plus if you just look at Dr. Tollefson's 15 report, the Fava stuff, the Jick study, the Warshaw 16 study, were all in his report, all epidemiology 17 studies. It is not like this is some kind of new 18 issue that's come up. That's not the case. 19 Whether there are any good controlled clinical 20 trials and whether there are any good epidemiology 21 studies have been issues in this case from the very 22 beginning, and Mr. Vickery's claim that he is 23 surprised and was amazed that we would bring up 24 epidemiology studies that are, in fact, disclosed in 25 expert reports, just doesn't hold water. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2404 1 So I cannot represent my client and 2 cross-examine this doctor if she goes on the stand 3 this afternoon or if she goes on the stand tomorrow or 4 if she goes on the stand next week. I haven't the 5 vaguest idea what to ask her because I don't know what 6 she's going to say. I don't know anything about her, 7 and it would be grossly unjust to permit the plaintiff 8 to do that. 9 Now, with respect to Dr. Maris, I mentioned a 10 little bit before, Dr. Maris is a classic and I beg 11 the Court's indulgence about using the word, but a 12 sandbag, holding Dr. Maris' back when he's already 13 formed his report and then disclosing him as a 14 so-called rebuttal expert later on. All one really 15 has to do is look at Dr. Maris' report and ask, is he 16 rebutting anything? His report is all of the issues 17 that were in plaintiffs' case in chief. He's just one 18 more expert. 19 Does Prozac cause suicidality? It leads to 20 akathisia. What does he do? He cites Teicher and 21 Rothschild. That's certainly brand new. It wasn't 22 the depression that caused this. It wasn't -- I mean, 23 you need Prozac to cause this, lots of medical 24 literature. And he cites, if you read his list of 25 article sites, the same articles that Dr. Healy and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2405 1 Dr. Shlensky cited, same thing. The only thing that's 2 new is Dr. -- is Paragraph 4 of his report where he 3 says he wants to opine that the other medications 4 Mr. Forsyth was taking did not cause his suicide, and 5 of course, Lilly has offered no evidence on that issue 6 so there's nothing to rebut. We've made no claim that 7 some other medication caused him to perform these 8 acts, so there's nothing to rebut. 9 So on both of the doctors, I'll just say 10 that -- well, let me raise one more thing. If there's 11 any claim that the subject of homicide/suicide and the 12 study of the joint event of homicide/suicide is 13 somehow a new event, a new issue that we raised in our 14 case, couldn't be further from the truth because 15 Dr. Healy gave testimony about it. And I asked 16 Dr. Maris when I deposed him, "You know anything about 17 this homicide/suicide literature?" And he said, "Oh, 18 sure." And then I said, "But did you say anything 19 about it in your report? No." 20 So Dr. Maris can't now claim, oh, now, I'm the 21 expert on homicide/suicide and I want to talk all 22 about it and rebut what Dr. Tardiff said in Lilly's 23 case because he didn't come forward in his report and 24 talk about it at all. That's not an appropriate 25 subject for rebuttal. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2406 1 The bottom line is Dr. Maris just doesn't rebut 2 anything. Everything he is saying are issues that are 3 issues part of plaintiffs' case in chief. That, that 4 it's not rebuttal and also for the fact that I believe 5 it is fairly characterized as inappropriate listing as 6 going out and finding your expert knowing you're going 7 to list him, having him write his report, form his 8 opinions, but hold him back until the other side lists 9 and then say, oh, now he's rebuttal. 10 The concept of rebuttal doesn't mean the 11 plaintiff automatically gets to go first and last. 12 That's not what it means. And that's the engineered 13 attempt that's going on here with Dr. Maris, and it's 14 not appropriate. It's not fair. It's not what the 15 system was designed to do with respect to rebuttal. 16 I'll let Ms. Mangrum address the Dr. Beasley issues. 17 MS. MANGRUM: Your Honor, I read last night the 18 plaintiffs designations of Dr. Beasley's testimony 19 from the Fentress case, and I've done my best in 20 Exhibit E to set out the substance of their 21 designation as well as our objection, and I think all 22 of the objections fall into the two categories that 23 Mr. See just mentioned; that is, they're not issues 24 that were raised by Lilly in this case, such as 25 testimony about akathisia. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2407 1 Lilly never raised or suggested to the Court or 2 to the jury that Prozac causes akathisia. We didn't 3 raise these issues, so they aren't proper rebuttal -- 4 for rebuttal testimony. Secondly, if they do deal 5 with issues that were raised by Lilly, such as the 6 Beasley meta-analysis, Dr. Beasley's testimony on 7 those issues are not inconsistent with the testimony 8 already given by Dr. Tollefson, and therefore, would 9 be cumulative and absolutely improper for rebuttal 10 testimony. 11 I think the best we could do is to go through 12 these categories, if the Court would like, one by one, 13 but I can assure the Court that they both fall within 14 those two categories of improper rebuttal testimony. 15 If the Court has specific questions about -- 16 THE COURT: I haven't had a chance to go 17 through Table E. I'll have to do that tonight. 18 MS. MANGRUM: Okay. Just as a few examples, 19 there's the issue of which is more proper when you're 20 trying to determine causation, controlled clinical 21 trials or case reports? That has been explored to the 22 **endth degree in this trial. It was addressed by 23 Dr. Tollefson in this trial, and what Dr. Beasley has 24 said about it is absolutely consistent and no 25 different from what Dr. Tollefson told the jury. PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2408 1 And I respectfully request that Beasley's 2 designations be stricken and not be allowed to be read 3 to the jury, because it will just be cumulative and is 4 not proper rebuttal testimony. 5 MR. VICKERY: Your Honor, I don't know if you 6 want a further response, but I would like to respond 7 to two things. One, with respect to Dr. Hoepfel, her 8 testimony would be very brief. I would certainly be 9 glad for Mr. See to interview her, to take her 10 deposition. We're talking about very, very brief 11 testimony. I'll ask all the questions in the 12 deposition that I would ask if she was on the stand, 13 and Mr. See can have a looksee (phonetically), if you 14 will, this evening before she goes on. 15 With respect to Dr. Maris, I would say this 16 about sandbagging, when we started the trial on 17 February 26th and the Court asked Mr. See why he kept 18 the Jick declaration so long before filing his second 19 motion for reconsideration, you then asked, well, do 20 you have a comment about that? And I deferred, Your 21 Honor, because I was afraid my comment would be of the 22 nature of the ones we just heard from Mr. See. 23 I find it amazing that he would say this 24 about -- particularly about my colleague Mr. Downey. 25 Mr. Downey is not here. He was the one involved at PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2409 1 the time of the designation, but the notion that 2 Mr. Downey was in some way sandbagging Mr. See when he 3 didn't get the full report for Dr. Maris done as part 4 of the case in chief and when he decided then to 5 designate him as a rebuttal witness, I think is 6 unfair. It's Lilly's case that depression causes 7 this, and that's why I want to call this man who is 8 the preeminent expert in the field of suicidology to 9 explain to the jury that what Lilly is saying is 10 simply wrong. 11 THE COURT: All right. I'm going to take a few 12 minutes. Let's take a break. I want to review this 13 case that you've given me. We'll take a break at this 14 point. 15 (Whereupon, a recess was taken at 3:00 p.m.) 16 THE COURT: First off, with respect to 17 Dr. Hoepfel, the Court is not going to allow her to 18 testify. She was not designated as a rebuttal expert 19 witness, and does not comply with the Court's 20 scheduling order which said that "All witnesses may be 21 called solely to contradict or rebut the evidence of a 22 witness identified by another party pursuant to 23 Subparagraphs A and B here and above shall occur 24 within 30 days after the disclosure by the other 25 party." PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2410 1 The Court finds that the Goldfinger decision is 2 distinguishable. There the plaintiff called three 3 employees of the defendant. These were not expert 4 witnesses. The Court finds that -- also, that this 5 would be improper rebuttal testimony that is in 6 violation of the Court's orders and does not comply 7 with Federal Rules of Civil Procedure 26(a)2 or the 8 local rules either. And it would cause unfair 9 prejudice to Lilly and under 403 the Court is not 10 going to permit it. It would be cumulative. And the 11 Court agrees with the other grounds asserted by Lilly 12 with respect to Dr. Hoepfel. And one reason why I 13 wanted to make this ruling at this point would be to 14 release Dr. Hoepfel so that she would not have to stay 15 over another day. 16 MR. VICKERY: She appreciates -- she probably 17 appreciates the Court's ruling and the time of the 18 Court's ruling, Your Honor, and we certainly 19 appreciate the latter one. 20 THE COURT: With respect to Dr. Maris, the 21 Court has already entered an order that neither of you 22 mentioned with respect to the motions in limine 23 regarding Dr. Maris as a rebuttal witness. The Court 24 will permit Dr. Maris to testify consistent with its 25 earlier order, but only to rebut Lilly's expert PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2411 1 testimony in evidence that Mr. Forsyth's depression, 2 absent Prozac, led to his suicide and homicide. The 3 Court will not permit Dr. Maris to testify as to 4 causation, as to Prozac causing akathisia and/or 5 suicide or homicide. That would be improper rebuttal. 6 The Court will not permit it under 403. It would be 7 cumulative. 8 As to Dr. Beasley's deposition, the Court will 9 allow that for proper rebuttal, and the Court has not 10 reviewed Table E as to whether -- to what extent there 11 is proper rebuttal. The order -- the Court's order 12 did not require designation for depositions for 13 rebuttal, and Dr. Beasley was on Lilly's list, as well 14 as the plaintiffs' list, so there's no surprise or 15 unfair prejudice to Lilly. And moreover, Lilly 16 resisted plaintiffs' request to have him brought here. 17 So we'll have to -- I'm going to have to review 18 that Table E this evening, and then we'll go over that 19 tomorrow. How long will the reading of this 20 deposition take this afternoon? 21 MR. SEE: This is only a guess, but my guess is 22 about 40 minutes, 30 to 40 minutes. 23 THE COURT: I wonder if maybe we ought to let 24 the jury go for the afternoon and -- 25 MR. SEE: I'd rather do that then cut it and PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2412 1 read only half. 2 THE COURT: And start in the morning. 3 MR. SEE: Yeah. 4 THE COURT: I don't know -- how long do you 5 think you'll be with Dr. Maris? 6 MR. VICKERY: I would think an hour or less, 7 Your Honor. 8 THE COURT: Is that agreeable, that we'll start 9 again at nine tomorrow? 10 MR. VICKERY: That's fine. 11 MR. SEE: Sure. 12 THE COURT: All right. See you in the morning. 13 (Whereupon, the proceedings were adjourned at 14 3:35 p.m. to be reconvened on Thursday, 15 March 25, 1999 at 9:00 a.m.)) 16 17 18 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU 2413 1 C E R T I F I C A T E 2 --ooOOoo-- 3 I, TINA M. STUHR, Official Court Reporter, 4 United States District Court, District of Hawaii, 5 Honolulu, Hawaii, do hereby certify that the foregoing 6 is a correct partial transcript of proceedings in 7 Civil No. 95-00185ACK, Susan K. Forsyth, et al. vs. 8 Eli Lilly and Company, et al., at Honolulu, Hawaii, on 9 March 24, 1999, before the Honorable Alan C. Kay, 10 United States District Judge. 11 DATED: December 29, 1999. 12 13 ______________________________________ TINA M. STUHR, RPR, CSR #360 14 15 16 17 18 19 20 21 22 23 24 25 PACIFIC REPORTING SERVICES UNLIMITED, INC. (808) 524-PRSU