Karen L. BARTLETT. Plaintiff. v. MUTUAL. ... 2010 WL 638286 (2010)
`
`2010 WL 638286 (D.N.H.) (Expert Deposition)
`United States District Court, D. New Hampshire.
`
`Karen L. BARTLETT, Plaintiff,
`v.
`MUTUAL PHARMACEUTICAL COMPANY, INC. and United Research Laboratories, Inc., Defendants.
`
`No. 08-CV-358-JL.
`February 20, 2010.
`
`Videotape Deposition of: Robert J. Valuck, Ph.D.
`
`Case Type: Contracts » Warranty
`Case Type: Contracts » Warranty-Implied
`Case Type: Fraud & Misrepresentation » Fraud - Fraud & Misrepresentation
`Case Type: Products Liability » Pharmaceuticals
`Jurisdiction: D.N.H.
`Name of Expert: Robert J. Valuck, Ph.D., R.Ph.
`Area of Expertise: Health Care-Physicians & Health Professionals » PharrnacistiPharmacologist
`
`Representing: Defendant
`
`Appearances.
`
`For the Plaintiff: Keith M. Jensen, Esq.
`Jensen, Belew & Gonzalez, PLLC
`1024 North Main Street
`Fort Worth, Texas 76164
`Christine M. Craig, Esq.
`Shaheen & Gordon
`140 Washington Street
`Dover, New Hampshire 03821.
`
`For the Defendants: Joseph P. Thomas, Esq.
`Ulmer & Berne LLP
`600 Vine Street Suite 2800
`Cincinnati, Ohio 45202
`Stephen J. Judge, Esq.
`Wadleigh Stan & Peters, PLLC
`95 Market Street
`Manchester, New Hampshire 0310 1
`(Appearing Telephonically).
`
`Also Present: Kathleen Myers, Videographer.
`
`February 10, 2010
`
`U,S, (Jovernrnent VVorks,
`
`Page 1 of 96
`
`JAZZ EXHIBIT 2042
`Amneal Pharms. et al. (Petitioners) v. Jazz Pharms., Inc. (Patent Owner)
`Case IPR2015-00554
`
`

`
`Karen L. BARTLETT, Plaintiff, v. MUTUAL., 2010 WL638286 (2010)
`
`PURSUANT TO NOTICE, the videotape deposition of ROBERT J. V ALUCK, PH.D. was taken on behalf of the Plaintiff at
`555 17th Street, Suite 3400, Denver, Colorado 80202, on February 10,2010, at 9:01 a.m., before Sandra L. Bray, Registered
`Diplomate Reporter, Certified Realtime Reporter, and Notary Public within Colorado.
`
`EXAMINATION OF ROBERT J. V ALUCK, PH.D.: PAGE
`
`INDEX
`
`February 10,2010
`
`By Mr. Jensen ... 9
`
`TABLE
`
`INITIAL
`
`INITIAL
`
`DEPOSITION EXHIBITS: (Previously marked) ... REFERENCE
`
`418 Report: FDA Science and Mission at Risk ... 156
`
`419 Congressional testimony of Dr. Cassell concerning FDA Science and Mission at Risk ... 171
`
`423 Special Communication: The Research on Adverse Drug Events and Reports (RADAR) Project ... 171
`
`WHEREUPON, the following proceedings were taken pursuant to the Federal Rules of Civil Procedure.
`
`MR. JENSEN: And with your agreement, Joe, the videographer will say on the record and offthe record, ifthat's okay with you?
`
`MR. THOMAS: Yes, that's fine.
`
`(Recess taken, 9:01 a.m. to 9:09 a.m.)
`
`THE VIDEOGRAPHER: We're on the record on February 10th, 2010 at 9:09.
`
`EXAMINATION
`
`BY MR. JENSEN:
`
`Q. Please state your name for the record.
`
`ROBERT J. VALUCK, PH.D., having been first duly sworn to state the whole truth, testified as follows:
`
`Q. (BY MR. JENSEN) Please state your name for the record.
`
`A. Robert Valuck.
`
`Page 2 of 96
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`

`
`Karen L BARTLETT, Plaintiff, v. MUTUAL" 2010 Wl 638286 (ZOi0)
`
`Q. Is there anything that will prevent you today from giving your best testimony? Medications, sleep deprivation, any1hing
`like that?
`
`A.No.
`
`Q. Can/does sulindac cause SJS/TEN?
`
`A. I believe it can.
`
`Q. When did you first have that belief?
`
`A. Probably in the mid-'80s. It was during my training in pharmacy school. I don't know the exact date, but it would have been
`between 1984 and 1987, when I was in training.
`
`Q. You've been retained or hired in other litigations or cases -- legal cases besides this one, correct?
`
`A. Yes.
`
`Q. Okay. And in the past, you've provided opinions as stating whether or not a specific drug or drugs caused or did not cause
`a given adverse reaction, correct?
`
`MR. THOMAS: Objection to form.
`
`A. Yes. Yes.
`
`Q. (BY MR. JENSEN) In this case, you did not do so, correct?
`
`A. I was specifically asked and I opined on the strength of evidence or the existence of evidence as to whether sulindac may
`cause SJS/TEN at a higher rate relative to other drugs, and that's specifically what I opined on, but other than that, I did not
`address other questions.
`
`Q. Okay. Is what you just defined, whether or not sulindac has a higher association or a stronger relationship with SJS and TEN
`and any other NSAIDS the sole issue upon which you've been asked to opine in this case?
`
`A. That was one question. The other question was just generally can drugs cause SJS/TEN and are the NSAIDs, including
`sulindac, among those drugs, and then the final was the one I previously stated, which is is there any evidence to suggest that
`sulindac may be associated with a higher rate relative to other NSAIDs or other drugs.
`
`Q. Okay. The first one you just identified, can drugs cause SJS and TEN, you didn't attempt to conclude -- let me ask a new
`question. All drugs don't cause SJS and TEN, correct?
`
`MR. THOMAS: Objection to form, foundation.
`
`A. Not to my knowledge, no.
`
`Q. (BY MR. JENSEN) Conversely stated, Dr. Valuck believes that there's many drugs that people take that do not cause SJS
`and TEN, correct?
`
`A. I would state it that I'm not aware of any evidence that would suggest that all drugs cause SJS or TEN.
`
`Page 3 of 96
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`

`
`Karen l. BARTlETT, Plaintiff, v. MUTUAL., 2()10 WL 638286 (2010)
`
`Q. Okay. Were you asked to define which drugs cause SJS and TEN? Let's exclude NSAIDs for a moment. Let's stay off
`NSAIDs, and we'll come back to that. Excluding NSAIDs for purposes of my question, were you asked to define which drugs
`cause SJS and TEN and which drugs don't?
`
`A. No, I was not.
`
`Q. Beyond what you see a list in the medical literature frequently, such as AEDs and sulfa-based antibiotics, and NSAIDs, and
`Allopurinol -- that's, obviously, not a class, but a single medication -- has Dr. Valuck ever done anything beyond that to make
`a determination in your own mind as to which drugs cause and which drugs don't cause SJS and TEN?
`
`MR. THOMAS: Objection, form.
`
`A.No.
`
`Q. (BY MR. JENSEN) No, you have not?
`
`A.No.
`
`Q. Okay. No, you have not and no is a double negative. You have to state something affirmatively. No, you have not ever
`done that; is that correct?
`
`A. No, I have not specifically done that.
`
`Q. That could be a denial of no, you have not, right?
`
`A. I understand.
`
`Q. Is the materials you just handed to me before we began -- do you believe it to be a printout of all that was previously provided
`to the Mutual attorneys -- and I guess you understand provided to me -- on a CD or are there additional materials in here?
`
`MR. THOMAS: Objection to form.
`
`A. To my understanding, that's everything that was provided.
`
`Q. (BY MR. JENSEN) Okay. And how did you physically get these materials to Mutual counsel and when did you do that?
`
`MR. THOMAS: Objection to fonn, foundation.
`
`A. Copies were provided to them over the course of the last several months bye-mail, on DVD. Some of those, I reviewed the
`literature and found them. Some of those were provided to me as far as literature that may be useful to me, and that list was
`built over the last several months and then provided to them as we went along.
`
`Q. (BY MR. JENSEN) You'll get all these originals back -- are these copies for me that I can take or do you need all these
`originals back?
`
`A. Those are the only printed copies that I have, so I'd prefer to get them back.
`
`MR. JENSEN: Then we'll make sure the originals get back to you. Okay, Miss Court Reporter?
`
`Page 4 of 96
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`

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`Karen L. BARTLETT, Plaintiff, v. MUTUAL.., 2010 Wl 638286 (lOiO)
`
`MR. THOMAS: Those aren't copies for you to take. Those are copies to be marked and go with the transcript?
`
`MR. JENSEN: Correct.
`
`(Deposition Exhibits 1 and 2 were marked.)
`
`Q. (BY MR. JENSEN) Exhibit 1 is your report in this case, correct?
`
`A. Yes, that's correct.
`
`Q. Who created Exhibit B to your report, Exhibit 2?
`
`A. Exhibit B, I created that.
`
`Q. And other than the medical literature that's listed here, is there any other medical literature beyond this set forth in Exhibit
`B that you reviewed in relation to this case or this matter?
`
`A. Not in any detail, no.
`
`Q. Okay. In other words, you might have seen it, but you didn't really read it with interest? Fair?
`
`A. Correct.
`
`Q. Okay. And who created this tabbed set ofthis medical literature, this index of medical literature?
`
`A. That tabbed set was created by the attorneys or staff at Ulmer Berne.
`
`Q. And then presently, when did you get it from them?
`
`A. I believe that was probably in September or early October of2009.
`
`MR. JENSEN: Okay. For the record, I'm going to mark this as Exhibit 3, and if the witness gets his original back, that means
`I'm going to get a tabbed copy of 1 through 24, including the index, which I'm putting the sticker on Exhibit 3. So we'll call
`it 3-1 through 3-24.
`
`(Deposition Exhibit 3 was marked.)
`
`Q. (BY MR. JENSEN) So 3-16 is a copy of one of the only two reports mentioned in your report, correct, relating to medical
`literature publications mentioned in your report, correct?
`
`A. Yes.
`
`Q. And we can call it the '08 Mockenhaupt, right?
`
`A. That's correct.
`
`Q. And the only other publication mentioned in your report is the '03 Mockenhaupt, right?
`
`Page 5 of 96
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`

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`Karen L. BARTLETT, Plaintiff, v. MUTUAL.., 2010 WL 638286 (2010)
`
`A. That's correct.
`
`Q. Is it correct to state that prior to 2004, in your view, the best evidence ofthe relationship between sulindac, on the one hand,
`and SJS/TEN, on the other hand, was the '03 Mockenhaupt publication?
`
`MR. THOMAS: Objection to form.
`
`A. Yes.
`
`Q. (BY MR. JENSEN) Going back to the '08 Mockenhaupt, Number 16 in your tabbed book, I noticed the very last page in
`your exhibit talks about -- it was printed off -- can you read that to me, please?
`
`A. "Copyright of Journal ofInvestigative Dermatology is the property of Nature Publishing Group and its content may not be
`copied or e-mailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However,
`users may print, download, or email articles for individual use."
`
`Q. Thank you, sir. Did you ever print off or read the on-line tables for that '08 Mockenhaupt publication?
`
`A. No, I did not.
`
`Q. Did you know they were available to be read?
`
`A. No, I did not.
`
`Q. Okay. Ever heard of Dr. Judith Jones?
`
`A. I have heard of a Dr. Judith Jones, yes.
`
`Q. And who is the one you've heard of?
`
`A. A pharmacoepidemiologist and researcher.
`
`Q. Okay. And previously with the FDA?
`
`A. I believe so. I'm not entirely sure of her positions across her career.
`
`Q. Okay. Have you ever read any of her publications?
`
`A. From time to time, yes.
`
`Q. Okay. Did you know that since she's left the FDA, when she's been retained in cases where there's a drug company defendant,
`she's universally, best anyone can tell, always testified on behalf ofthe drug company and not on behalf ofthe patient?
`
`MR. THOMAS: Objection, form and foundation.
`
`A. No, I'm not really aware of any of the specifics of cases that she mayor may not have testified or been retained on.
`
`(Deposition Exhibit 4 was marked.)
`
`Page 6 of 96
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`

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`Karen l. BARTLETT, Plaintiff, v. MUTUAL., 2010 WL 638286 (2010)
`
`Q. (BY MR. JENSEN) Do you know how many times the Mutual attorneys who hired you in this case have used her in their
`cases?
`
`MR. THOMAS: Objection; form, foundation.
`
`A. No, I'm not aware.
`
`Q. (BY MR. JENSEN) Were you the Mutual attorneys in this case have retained her as a defense expert in some or all of
`their cases?
`
`A.No.
`
`MR. THOMAS: Objection, form.
`
`A. No, I was not aware.
`
`Q. (BY MR. JENSEN) Exhibit 4 is an article by her. Take a moment to look at that, please.
`
`MR. THOMAS: Does "take a moment to look at it" mean you want him to read it?
`
`MR. JENSEN: No.
`
`MR. THOMAS: So you don't have to read it.
`
`A. Okay.
`
`(Deponent perused the exhibit.)
`
`Q. (BY MR. JENSEN) Have you ever seen the algorithm -- I think it's Table 2 in that report -- that sets forth an FDA algorithm
`for determining causation?
`
`MR. THOMAS: Objection; fonn, foundation.
`
`A. I don't recall having seen this specific algorithm in this specific form.
`
`Q. (BY MR. JENSEN) Okay. Have you seen algorithms like that?
`
`MR. THOMAS: Objection, form.
`
`A. Have seen algorithms that would, I suppose, be designed to attempt to assess possible causality, yes.
`
`Q. (BY MR. JENSEN) Okay. And do you use such algorithms when you make assessments of causality in an individual case?
`
`MR. THOMAS: Objection; form, foundation.
`
`A. I have used algorithms in the past for application of criteria to detennine possibilities or accrued likelihoods of potential
`causality, but most of my work has not been direct application to individual case reports through that application of algorithms.
`
`Q. Okay. Do you use the Bradford Hill criteria?
`
`Page 7 of 96
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`

`
`Karen L. BARTLETT. Plaintiff, v. MUTUAL .• 2010 WL 638286 (2010)
`
`MR. THOMAS: Objection to form.
`
`A. I have used the Bradford Hill criteria, yes.
`
`Q. (BY MR. JENSEN) Have you used that every time you've been hired in a legal case to assess whether or not the drug or
`drugs caused the effect in question?
`
`A. I don't recall whether I've used them in every case. I'm not certain if I've used them in every case. I have used them.
`
`Q. As you can see under Figure 2 on Page 62, it's described as an algorithm for establishing causal relationship between drug
`and event used by FDA's Division of Drug Experience. Do you see that?
`
`MR. THOMAS: Objection, form.
`
`A. Yes, I see that.
`
`Q. (BY MR. JENSEN) To your knowledge -- and, this, of course, was published back in 1982, many years ago. To your
`knowledge, has that algorithm ever been changed by the FDA in terms of the algorithm the FDA uses to establish a causal
`relationship between a drug and an event?
`
`MR. THOMAS: Objection; form, foundation.
`
`A. I don't know.
`
`Q. (BY MR. JENSEN) And we can go through each box, but do you agree that a fair summary of the boxes is, first, to
`determine whether or not there's a temporal association between a drug and an event; second, to figure out whether there's
`been a dechallenge or withdrawal of the drug in question; third, did the event abate or stop when the drug was withdrawn or
`dechallenged, and, fourth, was there a rechallenge, i.e., a reintroduction of the drug or not? Stopping there, is that a fair summary
`of the questions they asked so far?
`
`MR. THOMAS: Objection, fonn.
`
`A. Yes.
`
`MR. THOMAS: You're welcome to take your time to read it if you need to.
`
`A. Yes, it appears to be a fair summary of what's in the boxes, yes.
`
`Q. (BY MR. JENSEN) And then it says been no rechallenge, i.e., the drug has not been reintroduced and the answer is no, could
`the event be due to an existing clinical condition a person might have, whatever condition is being studied, and if answer is no
`to that, it says, "Causal relationship considered probable." Do you see that, sir?
`
`MR. THOMAS: Objection, form.
`
`A. Yes, I do see that.
`
`Q. (BY MR. JENSEN) My question for you is, would you consider a causal relationship probable based upon your analysis
`of a drug or drugs and an event based upon those four questions or five being answered that way? Just straight down the first
`
`Page 8 of 96
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`

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`Karen L. BARTLETT, Plaintiff, v, MUTUAL.., 2010 Wl638286 (2010)
`
`four and no for rechallenge and could there be an existing clinical condition, if the answer is no, you would consider the causal
`relationship probable? That's my question. Yes or no?
`
`MR. THOMAS: Objection, form.
`
`A. I would consider the causal relationship at that point to be possible.
`
`Q. (BY MR. JENSEN) Right. And in saying that, do you understand -- and how are you defining "probable" in answering
`that question?
`
`MR. THOMAS: Objection, form.
`
`A. I suppose probable in this case would be more likely than not.
`
`Q. (BY MR. JENSEN) Okay. And then, do you know what it means when they go down to the bottom box there and they say
`highly probable? Is that much more likely than not?
`
`MR. THOMAS: Objection to form, foundation.
`
`A. Having not read this specific algorithm or being aware of this specific algorithm or its application prior to this time, I don't
`know how they define "probable" versus "highly probable."
`
`Q. (BY MR. JENSEN) And then, because this algorithm defines "probable" in the manner we just went through, do you disagree
`with the FDA's determination that if those four questions are answered -- or I guess three questions are answered yes and then
`two questions are answered no, which would be rechallenge and event due to an existing clinical condition, and they call that
`probable, do you disagree with that?
`
`MR. THOMAS: Objection to form, foundation, misstates the document.
`
`A. Again, I view it at that point as probable -- or, excuse me, possible.
`
`Q. (BY MR. JENSEN) And do you know that that has been the determining factor of whether an adverse event is listed as
`probable or not in many PDR labels, that they're based on this algorithm, in other words, if an adverse event is yes to the first
`three questions and no to the second two questions, then it makes it on the list of probable adverse reactions in a label?
`
`MR. THOMAS: Objection to form, foundation.
`
`A. No, I'm not specifically aware of the criteria the FDA uses in that case to apply algorithm-based assessment of case reports
`and transfer those to labeling.
`
`Q. (BY MR. JENSEN) Okay.
`
`A. That's not my area of expertise.
`
`Q. Fair enough. So is it fair to state that if, in fact, the FDA does use this algorithm to detennine when the word "probable" is
`used to describe an adverse event in a label, you don't know, A, whether that's true or, B, you have no expertise in determining
`what "probable" means in that regard in a PDR label?
`
`MR. THOMAS: Objection to fonn, foundation.
`
`Page 9 of 96
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`

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`Karen l. BARTLETT, Plaintiff, v. MUTUAL.., 20H) Wl638286 (2010)
`
`A. I think I'd like you to restate the question.
`
`Q. (BY MR. JENSEN) Sure. I'll add to it if you want me to.
`
`A. Yes.
`
`Q. If, in fact, the use of the word "probable" in describing adverse events in one -- many PDR labels is based upon this FDA
`algorithm, i.e., the first three questions are answered yes, the second two are answered no, then you get to the box, considered
`-- causal relationship considered probable, you don't know whether that's true or not, correct?
`
`MR. THOMAS: Objection to form, foundation.
`
`A. Again, my interpretation would be it's possible.
`
`Q. (BY MR. JENSEN) Right. And now, I'm asking you, you don't know if the FDA has used this algorithm in defining when
`"probable" is used in a PDR label to describe an adverse event, correct?
`
`MR. THOMAS: Objection to fonn.
`
`A. I see. That's correct. Correct.
`
`Q. (BY MR. JENSEN) And you have no expertise, therefore, to tell anyone when "probable" is used in a label whether it means,
`as one might expect, that the person is communicating something that's more likely than not or whether it's actually based upon
`this FDA algorithm, correct?
`
`MR. THOMAS: Objection, form.
`
`A. That's correct, I'm not sure the basis.
`
`Q. (BY MR. JENSEN) Okay. Have you ever seen -- strike that. You've read a lot ofPDR labels. You're a pharmacist, right?
`
`A. That's correct, I have read PDR labels.
`
`Q. Can you think of any description of an adverse event ever in a PDR label that's described as highly probable?
`
`A. I don't recall specifically, related to a specific case.
`
`Q. Is it fair to say you've seen "probable" a lot?
`
`A. I've seen "probable" used.
`
`Q. And now, we know that despite you being a pharmacist, you didn't know the definition of "probable" because it might have
`been from this algorithm, correct?
`
`MR. THOMAS: Objection; form, foundation.
`
`A. That's correct.
`
`Page 10 of 96
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`

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`Karen l. BARTLETT, Plaintiff, v, MUTUAL" 2010 WL 638286 (2010)
`
`Q. (BY MR. JENSEN) Okay. When did you last actively practice as a pharmacist?
`
`A. I believe I last practiced as a pharmacist in a dispensing capacity in 1994. My license is still current I practice in a research
`mentoring capacity, have done, since that time.
`
`Q, And were you a pharmacist in Colorado when you last were a dispensing pharmacist?
`
`A. No. The last location where I was a dispensing pharmacist was in Chicago.
`
`Q. And where was that?
`
`A. That was, I believe, at a home infusion therapy companyin suburban Chicago in the last couple of years that I was in graduate
`school, between perhaps 1992 and 1994 or thereabouts.
`
`Q. When you say graduate school, you mean UI Chicago, they call it?
`
`A. University of Illinois at Chicago, yeah.
`
`Q. In Halsted?
`
`A. Yes.
`
`Q, And what pharmacy were you a dispensing pharmacist at?
`
`A. The company I was with moved, but the last location, I believe, was Northbrook, Illinois, and prior to that, it may have been
`Elk Grove or -- I don't remember before that, but the company moved locations. I believe it was Northbrook.
`
`Q. You've already told me that prior to 2004, the '03 Mockenhaupt paper was the best evidence about the relationship or
`strength of the relationship between sulindac and SJS/TEN. Now, please tell me, was there anything else that you found that
`was important to you -- define "important" however you want -- important to you in defining whether or not there was a causal
`relationship between sulindac, on the one hand, and SJS/TEN, on the other hand, which you've already testified you believe
`there is?
`
`MR. THOMAS: Objection, form.
`
`A. Let me think. Other than those --
`
`Q. (BY MR. JENSEN) Not those. Only one because I'm talking about prior to '04.
`
`A. Prior to '04. I can't think of anything else other than -- again, as I stated before, my training was when I was first taught
`about that and learned about that
`
`Q. Yeah, yeah, yeah, you can be told all sorts of things that mayor may not have epidemiological support for them. That's
`why you do epidemiology, right?
`
`MR. THOMAS: Objection, form.
`
`A. That's one reason, yes.
`
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`Karen L. BARTLETT, Plaintiff, v. MUTUAL.., 2010 Wl 638286 (2010)
`
`Q. (BY MR. JENSEN) Yeah. So that's my question. Prior to '04, other than the '03 Mockenhaupt report, is there anything
`of importance to your mind, obviously from a scientific epidemiological standpoint, that addressed the relationship between
`sulindac, on one hand, and SJS/TEN, on the other hand?
`
`MR. THOMAS: Objection, form.
`
`A. Nothing of-- nothing of significance, no.
`
`Q. (BY MR. JENSEN) Okay. So -- and is that one of the reasons why you only cited two papers in your report, the '03 and '08
`Mockenhaupt, because there was nothing else -- now, I'm asking a new question.
`
`The new question is, is the reason why you only cited two papers in your report, the '03 and '08 Mockenhaupt, is because
`there's nothing else of significance at any time before and after those two publications in your estimation epidemiologically,
`scientifically speaking about the relationship between sulindac, on the one hand, and SJS/TEN, on the other hand?
`
`MR. THOMAS: Objection, form.
`
`A. I referred specifically to those two because I believe those constitute the best available epidemiologic evidence and that the
`others don't, don't represent as strong of an evidence base as those two particular studies do. That's why I singled them out.
`
`Q. (BY MR. JENSEN) Now, I've got to address the portion of your answer where you said other things don't represent as strong
`as evidence-based. Is there any other case control study that you know of or RCT, randomized clinical trial, that's ever been
`done that in any way in your view has any relevance to the relationship between sulindac, on the one hand, and SJS/TEN, on
`the other hand?
`
`MR. THOMAS: Objection, form.
`
`A. Not that I'm aware of, no.
`
`Q. (BY MR. JENSEN) Can a case report in and of itself with a positive rechallenge or a dechallenge/rechallenge, positive for
`the rechallenge, however you want to put it, in and of itself demonstrate a causal relationship?
`
`MR. THOMAS: Objection to fonn.
`
`A. I don't believe so, no.
`
`Q. (BY MR. JENSEN) And you've thought about that question before I asked it, fair?
`
`MR. THOMAS: Objection, fonn.
`
`A. I suppose over a period of time, yes, not specifically, but--
`
`Q. (BY MR. JENSEN) Sure.
`
`A. -- I suppose, yes.
`
`Q. Well, that would be one of the things that academicians like yourself at ISPE would talk about, fair?
`
`MR. THOMAS: Objection, form.
`
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`Karen l. BARTLETT, Plaintiff, v, MUTUAL" 2010 Wl638286 (2010)
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`A. I suppose, among a wide variety of things.
`
`Q. (BY MR. JENSEN) Well, let's not suppose. You've talked about that with other IPSE members, right?
`
`MR. THOMAS: Objection to the fonn.
`
`A. I don't recall specific conversations, but I may have.
`
`Q. (BY MR. JENSEN) Are you a member or fellow of ISPE?
`
`A. I'm a member of IPSE.
`
`Q. And when did you become a member?
`
`A. I believe I became a member in the middle of 1994.
`
`Q. Okay.
`
`A. I believe.
`
`Q. Can a case report with a positive rechallenge provide strong evidence of a causal relationship?
`
`A. I don't believe so, no.
`
`Q. Okay. Can a case report with a positive rechallenge provide evidence of a causal relationship?
`
`A. I would say it can provide initial suggestion of a possible relationship.
`
`Q. So is it correct to state -- strike that. Do you agree with me, speaking in tenns of the hierarchy of evidence, that if we went
`RCT, case control study, case series, case report, the strongest evidence you could ever get from a case report about a possible
`causal relationship between a drug and an event would be a positive rechallenge?
`
`MR. THOMAS: Objection; fonn, foundation, misstates the hierarchy of evidence.
`
`A. I think I would disagree and state that a case report with, you know, other criteria, other Bradford Hill criteria met provides
`stronger -- relatively speaking stronger evidence, but that it is still limited to a suggestive role.
`
`Q. (BY MR. JENSEN) Give me an example of a case report that provides stronger evidence of a causal relationship than a
`positive rechallenge.
`
`MR. THOMAS: Objection, fonn.
`
`A. Don't have any specific case report in mind.
`
`Q. (BY MR. JENSEN) You don't have to think of one. Just teach us.
`
`MR. THOMAS: Objection.
`
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`Karen L BARTlETT, Plaintiff, v. MUTUAL.., 20Hl WL 638286 (2010)
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`Q. (BY MR. JENSEN) You just testified to it, so tell us why it's true.
`
`MR. THOMAS: Objection, form.
`
`A. There would be other criteria that would be applied in addition to a de challenge or a rechallenge that would suggest something
`may have a somewhat higher likelihood of being causal. So those things might include assuring temporal sequencing that drug
`preceded event, taking blood concentrations of a drug to assure that the drug was consumed as suspected, establishment of
`a clear mechanism of action between the drug and the effect. Replication would be desirable in further strengthening. Those
`types of things would -- again, within the context of the strength of a case report, would give it higher relative strength to a
`case report without those other criteria being present.
`
`Q. (BY MR. JENSEN) And when you just said replication, is that by other case reports, you mean? You don't mean replication
`by positive rechallenge? Because that's what we were distinguishing.
`
`A. That's correct.
`
`Q. So you defined four things for me; temporal relationship, blood concentrations to confirm use, mechanisms of action being
`lmown, and replication through other case reports; that means a case series. So we're talking about case reports. You testified
`that there can be case reports that had stronger evidence of a causal relationship than a positive rechallenge. So actually you've
`only listed three. Are there any other you want to list that actually support your opinion you gave?
`
`MR. THOMAS: Objection to form.
`
`A. I suppose dose-response, if a dose would arguably be associated with a higher rate and/or severity of an event, whatever the
`event is. And those are the ones that come to mind.
`
`Q. (BY MR. JENSEN) What about duration-response?
`
`A. It's possible. Again, I would lump the duration under cumulative dose-response just in general terms, the strength of the
`dose, meaning the number of milligrams or the potency ofthe product or those types of things, then cumulative duration being
`over a period of time.
`
`Q. Dose and duration-response are obviously inter-related?
`
`A. Correct.
`
`Q. Okay. Duration response can provide evidence either because it's a long time, like smoking for 30 years, or because in certain
`instances, everyone seems to get it within a certain period of time, fair?
`
`MR. THOMAS: Objection to form.
`
`A. Could be. Could be. It would all depend on the specifics.
`
`Q. (BY MR. JENSEN) Anything else that you want to list for me -- you've now just given me four -- that support your testimony
`that a case report, one, can provide stronger evidence of a causal relationship than a positive rechallenge? The four you gave
`me are temporal, confirmed use by blood concentration, mechanisms of action, and higher dose is increased severity.
`
`MR. THOMAS: Objection to form.
`
`Page 14 of 96
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`Karen L BARTLETT, Plaintiff, v. MUTUAL., 2010 WL 638286 (2010)
`
`A. No, none other to add at this time.
`
`Q. (BY MR. JENSEN) Okay. Can a case report in and of itself, any case report, demonstrate a causal relationship?
`
`A. No, I don't believe so.
`
`Q. Okay. Can a case -- any case report provide strong evidence of a causal relationship?
`
`A. I don't believe it can provide strong evidence. I believe it can provide a suggestion of a possible relationship.
`
`Q. Okay. And the third question, can a case report -- any case report in and of itself provide evidence of a causal relationship?
`
`A. I don't believe so, no.
`
`Q. What about case series? Can a case series demonstrate a causal relationship?
`
`MR. THOMAS: Objection to form.
`
`A. I don't believe so, in and of itself, no.
`
`Q. (BY MR. JENSEN) Okay. Can a case series provide strong evidence of a causal relationship?
`
`A. I don't believe so, no.
`
`Q. Okay. Can a case series provide evidence of a causal relationship?
`
`A. I believe a case series can provide suggestive evidence of a possible causal relationship.
`
`Q. Okay. Let's go back to that discussion we had about more likely than not. Because case series and case reports at very best
`can provide a suggestion of a possible causal relationship in your mind in just a case series, now that we've gone through every
`type that could provide evidence, do you agree with me that prior to '03 Mockenhaupt, had you been asked the question whether
`there was a more-likely-than-not causal relationship between sulindac, on the one hand, and SJS/TEN, on the other hand, you
`would have said, "No, there's not evidence of a more-likely-than-not causal relationship" --
`
`MR. THOMAS: Objection to form.
`
`Q. -- because that's all there was, case series and case reports?
`
`MR. THOMAS: Objection to fonn.
`
`A. I don't know. I wasn't asked that question at that particular time, but I suppose in hindsight that there would not be any
`reliable, solid evidence that a causal relationship exists.
`
`Q. (BY MR. JENSEN) Okay. And do you agree because there would not have been any reliable scientific evidence that a causal
`relationship exists, it would have been your view that it was not more likely than not that sulindac causes SJS/TEN prior to
`the existence of '03 Mockenhaupt?
`
`MR. THOMAS: Objection, form.
`
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`Karen l. BARTLETT, Plaintiff, v. MUTUAL., 2010 Wl638286 (2010)
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`A. My conclusion would be that it -- based on the evidence, that it's possible, but I would not, based on the evidence, use any
`other word than "possible." I would not go to any other.
`
`Q. (BY MR. JENSEN) Because you wouldn't use any other word than "possible," you agree you would not have stated that it
`was more likely than not that sulindac caused SJS/TEN prior to '03 Mockenhaupt, correct?
`
`MR. THOMAS: Objection, form.
`
`A. That's correct.
`
`Q. (BY MR. JENSEN) Okay. Did you make any attempt to determine -- strike that. How many NSAIDs have been taken off
`the market?
`
`A. I don't know the exact number.
`
`Q. What's your best understanding?
`
`A. Of that number--
`
`Q. Yes, sir.
`
`A. -- of how much? A few to a handful. I really don't know the number.
`
`Q. Okay. Did any of the medical literature you reviewed on your Exhibit B address that?
`
`A. I do recall seeing that mentioned. I don't recall specifically which article or articles mentioned withdrawal of specific products,
`but --
`
`Q. And did the article or articles talk about a few or a handful?
`
`A. Talked about a few, as I recall. Mentioned a few.
`
`Q. Okay. And did you make any effort to find out -- and few, are we tal