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