The following is excerpted from the June 2005 deposition testimony of Deborah Shapiro, senior biostatistician for Merck & Co. In the testimony, regarding a clinical analysis that linked Vioxx with vascular adverse effects, Shapiro acknowledges that certain information was not given to the U.S. Food and Drug Administration (FDA). New Jersey Superior Court Judge Carol Higbee called the testimony the only evidence sufficient to support a punitive damages verdict against Merck. Questioning Shapiro for the plaintiffs is Shanin Specter of Kline & Specter, PC.

6 Dr. Shapiro, good morning. I haven't
7 seen you for a while.
8 What documents have you reviewed in
9 preparing for today's deposition?
10 MR. MAYER: Objection. You can
11 answer that question to the extent that you reviewed
12 documents in preparation for deposition that
13 refreshed your recollection.
14 MR. SPECTER: The rules are changing
15 apparently. The last two times we've had this
16 question asked, it hasn't been objected to with an
17 instruction not to answer limiting it to documents
18 that refresh the witness' recollection.
19 We'll start with the modification Mr.
20 Mayer suggested.
21 MR. MAYER: Dr. Shapiro, you can
22 answer the question.
23 THE WITNESS: I looked at the minutes
24 from the data safety monitoring board meetings.
25 BY MR. SPECTER:

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1 Q. I'm sorry, from the what?
2 A. Data safety monitoring board
3 meetings, DSMB.
4 Q. For VIGOR?
5 A. Yes.
6 Q. Anything else?
7 A. Yes. Looked at a PowerPoint
8 presentation from the October 2000 consultants
9 meeting.
10 Q. Which meeting?
11 A. Cardiovascular consultants.
12 Q. Was there more than one meeting in
13 October of 2000?
14 A. Not with cardiovascular consultants.
15 We had other consultant meetings, and I'm not sure
16 what month.
17 Q. Is this the one from October 18th?
18 A. Yes.
19 Q. Go ahead, please.
20 A. I looked at an e-mail from Briggs
21 Morrison.
22 Q. What e-mail was that?
23 A. Talking about the Konstam manuscript.
24 Q. Is this the one where he stated a
25 concern on his part that the data were being fitted

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1 into the hypothesis?
2 MR. MAYER: Objection to form.
3 THE WITNESS: I would have to look at
4 the e-mail to have his exact wording.
5 BY MR. SPECTER:
6 Q. Does that ring a bell with you, that
7 concept?
8 MR. MAYER: Object to the form.
9 THE WITNESS: There was something
10 about a hypothesis in the data.
11 BY MR. SPECTER:
12 Q. One being fit into the other?
13 A. Something like that.
14 MR. MAYER: Object to the form.
15 BY MR. SPECTER:
16 Q. That's the one that you looked at?
17 A. Yes.
18 Q. What else did you look at?
19 A. I'm thinking.
20 Q. Take your time.
21 A. The meta-analysis that we submitted
22 to the FDA in, I believe, January 2001, the first
23 one we submitted.
24 Q. Okay.
25 A. The Juni meta-analysis manuscript or

631
1 published paper. Memo from Dr. Thomas Musliner.
2 Q. Which one is that?
3 A. 1996.
4 Q. What else?
5 A. The cardiovascular adjudication
6 standard operating procedure.
7 Q. Which one?
8 A. There's only one.
9 Q. What's the date of it?
10 A. I don't know.
11 Q. How about the year?
12 A. I don't know.
13 Q. How about the decade?
14 A. I'm not positive of that either. I'm
15 serious. It might be '99. Well, it had to be
16 before 2000 because it was attached to the protocol.
17 I don't know.
18 Q. So --
19 A. There was only one.
20 Q. -- it would be the decade of the
21 '90s; correct?
22 A. Yes.
23 Q. Was the Musliner memo that you looked
24 at from the one the 21st of November of '96,
25 addressed to Friedman, Nies and Spector, no

632
1 relation?
2 A. I think so, but I didn't look closely
3 at the date or the "to" list.
4 Q. What else?
5 A. Merck policy and procedure on the
6 data safety monitoring board's Appendix 2 to the
7 MAPP. We call them MAPPs, Medical Affairs Policies
8 and Procedures.
9 Q. What else?
10 A. I can't think of anything else.
11 Q. Did you get that MAPP policy and
12 procedure?
13 A. What do you mean?
14 Q. Well, did you request it?
15 A. No.
16 MR. MAYER: I object to that
17 question. I'm not sure what your question is
18 asking, but if you are asking what conversations she
19 had with counsel, I object.
20 MR. SPECTER: I wasn't.
21 MR. MAYER: Okay. I'll object to it
22 because it's vague.
23 MR. SPECTER: Well, it's been
24 answered.
25 BY MR. SPECTER:

633
1 Q. The Musliner memo of 1996, had you
2 seen that before you were deposed the first time?
3 A. I certainly had seen it before.
4 Q. Did you see it back in '99 and 2000
5 when you were working on the VIGOR trial?
6 MR. MAYER: Object to the form.
7 THE WITNESS: I can't remember when
8 the first time was that I saw it.
9 BY MR. SPECTER:
10 Q. Can you give me some idea of when the
11 first time was that you saw it?
12 A. Not really. I mean, I either saw it
13 before or during or after the VIGOR trial.
14 Definitely after. I can't remember if I saw it
15 before and during.
16 Q. When you say "definitely after" the
17 VIGOR trial, were --
18 A. After the unblinding.
19 Q. After the unblinding. Did you see it
20 around the time of the unblinding?
21 A. I don't remember when I first saw it.
22 Q. I'm not asking when you first saw it.
23 A. I know, but --
24 Q. I'm asking if you saw it around the
25 time of the unblinding.

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1 A. I don't recall.
2 Q. Well, do you think you saw it
3 sometime in 2000?
4 A. Yes.
5 Q. How would that have come to you in
6 2000?
7 A. Probably by e-mail, but I don't
8 remember.
9 Q. Why would you be looking at that?
10 A. Because of its background in
11 relationship to cardiovascular events.
12 Q. Now, Doctor, did Merck change the
13 standard operating procedure with respect to those
14 types of adverse events in the VIGOR trial that were
15 eligible for case adjudication?
16 MR. MAYER: Object to the form.
17 THE WITNESS: There was a change in
18 the list of adverse events, but I believe that
19 preceded VIGOR as far as I know. It preceded VIGOR,
20 because the first time I saw it, it was already in
21 place as is, and it was done certainly blinded. It
22 was done, to my understanding, because the other
23 terms weren't yielding any cases that were
24 appropriate for adjudication.
25 BY MR. SPECTER:

635
1 Q. So --
2 A. But that's the best of my
3 understanding, and I believe it happened before
4 VIGOR started.
5 Q. So, that would have been before early
6 '99?
7 A. I don't know exactly when, but I
8 believe it's dated on the document. The date is
9 provided on the document.
10 Q. Well, VIGOR started in early '99;
11 correct?
12 A. Yes.
13 Q. So, if the change occurred, it would
14 have occurred before early '99.
15 MR. MAYER: Object to the form.
16 BY MR. SPECTER:
17 Q. Is that correct?
18 A. I don't know exactly when the change
19 happened. It says it on the document. But when I
20 reviewed the document in the course of VIGOR, it had
21 already taken place, so...
22 MR. SPECTER: Let me mark a document
23 as Shapiro-51.
24 - - -
25 (Whereupon, Deposition Exhibit

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1 Shapiro-51, Memo 1-4-00, "Revised
2 version of the Standard Operating
3 Procedures for the Surveillance,
4 Monitoring, and Adjudication of
5 Thrombotic/Embolic Vascular Events in
6 Clinical Trials of COX-2 Specific
7 Inhibitors," MRK-ABC0000027 -
8 MRK-ABC0000040, was marked for
9 identification.)
10 - - -
11 BY MR. SPECTER:
12 Q. Can you identify the document for the
13 record, please?
14 A. I'll need to look at it first.
15 (Witness reviewing document.)
16 Q. The current question is, could you
17 please identify the document?
18 A. It's a document that describes some
19 changes that were being made to the standard
20 operating procedure for the CV adjudication.
21 Q. This would relate to VIGOR; is that
22 correct?
23 MR. MAYER: Object to the form.
24 THE WITNESS: All trials.
25 BY MR. SPECTER:

637
1 Q. All trials. That would include
2 VIGOR; is that correct?
3 A. Yes.
4 Q. Does it indicate when the change was
5 made with respect to changing the events that would
6 be subject to adjudication?
7 MR. MAYER: Object to the form.
8 THE WITNESS: It has a date that it's
9 written on, January 4th. It refers to revisions
10 that seem to have been started in December '99.
11 BY MR. SPECTER:
12 Q. Right.
13 A. But that is before VIGOR unblinding.
14 Q. Okay.
15 Well, before you told me that this
16 change was made before the VIGOR trial; correct?
17 MR. MAYER: That's not what she said.
18 THE WITNESS: When I saw it in order
19 to use it for analysis, it had already been made.
20 BY MR. SPECTER:
21 Q. In fact, the change occurred after
22 the results of most of the patient experience had
23 occurred with VIGOR since the trial in VIGOR
24 occurred starting in early '99 and proceeding
25 through the remainder of the year; correct?

638
1 MR. MAYER: Object to the form.
2 THE WITNESS: The trial was blinded.
3 No one knew the data. No one knew the treatment
4 groups except me and the data safety monitoring
5 board. The changes were made irrespective of any
6 knowledge of what was going on with VIGOR, and,
7 therefore, it's before VIGOR analysis. Whether the
8 data had been collected is not relevant to the fact
9 that it was done before any analysis was available
10 to anyone at Merck.
11 MR. SPECTER: Okay. I move to strike
12 that answer as being thoroughly nonresponsive.
13 BY MR. SPECTER:
14 Q. Let's look at the date, Dr. Shapiro,
15 that appears at Bates Stamp Number MRK-ABC00000034.
16 Are you with me?
17 A. It doesn't say 34.
18 Q. Well, it requires opening the
19 document, Doctor.
20 A. (Witness complies.)
21 Q. You see there that it lists the
22 events that are eligible for case adjudication;
23 correct?
24 MR. MAYER: Objection to the comment
25 that preceded the question. You may answer the

639
1 question.
2 THE WITNESS: It has a list of terms
3 that are to be sent for workup for adjudication.
4 BY MR. SPECTER:
5 Q. And the date of the document is
6 December 29th of '99; correct?
7 A. Yes.
8 Q. And crossed off the list are a
9 variety of events including congestive heart
10 failure; correct?
11 A. Yes.
12 Q. And it notes at the top or toward the
13 top of the document, "In the absence of other events
14 identifying adverse experiences (most of which are
15 likely to be serious adverse events), the following
16 events (marked in strikethrough font) will have a
17 low likelihood (in and of themselves) of being
18 thromboembolic events. They may follow
19 thromboembolic events, but alone do not represent
20 such events." Did I read that correctly?
21 A. Yes.
22 Q. And there were 1, 2, 3, 4, 5, 6, 7,
23 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21
24 events crossed off; correct?
25 A. I would have to go through and count

640
1 them. I am assuming you counted properly.
2 Q. Thank you.
3 And one of those is congestive heart
4 failure; correct?
5 A. Yes.
6 Q. Now, moving to March of 2000, we had
7 previously discussed that there had been a limited
8 unblinding on March 9th of 2000. Do you recollect
9 that?
10 A. Yes.
11 Q. Merck reported the results of VIGOR
12 to FDA in late March of 2000, along about March
13 26th. Do you recollect that?
14 MR. MAYER: Object to the form.
15 THE WITNESS: I don't recall the
16 exact date. I know it was in March of 2000.
17 BY MR. SPECTER:
18 Q. What did you do specifically with
19 respect to VIGOR between March 9th and March 26th of
20 2000?
21 A. I did a lot of analyses.
22 Q. What did you do exactly?
23 A. Additional subgroup analyses is what
24 I recall best. I don't have specific recollections.
25 It's a long time ago.

641
1 Q. Did you look at anything aside from
2 the results of VIGOR?
3 MR. MAYER: Object to the form. You
4 may answer as best you can.
5 THE WITNESS: I looked at the results
6 that other people provided of other trials. I
7 looked at counts tables from the Alzheimer's trials.
8 I looked at count tables from, I believe ADVANTAGE,
9 but I'm not positive.
10 BY MR. SPECTER:
11 Q. What's a count table?
12 A. Counts of adverse experiences in the
13 different treatment groups.
14 Q. Was it segmented to a certain kind of
15 adverse experience?
16 A. Well, we specifically were looking at
17 cardiovascular, serious cardiovascular adverse
18 experiences to the best of my recollection.
19 Q. Did you look at deaths in
20 Alzheimer's?
21 A. I don't recall that, no.
22 Q. What else did you look at aside from
23 VIGOR and aside from the things that you've
24 described for me between March 9th and March 26th of
25 2000?

642
1 A. I believe that we looked at
2 cardiovascular events in the osteoarthritis database
3 that was submitted to the NDA.
4 Q. What else?
5 A. I can't remember anything else.
6 Q. Did you look at any data relative to
7 adverse events associated with naproxen in other
8 trials that other companies may have done?
9 A. I don't recall.
10 Q. Did you look at any trials or any
11 studies respecting other nonsteroidal
12 anti-inflammatories not including Vioxx?
13 MR. MAYER: Just to be clear, the
14 "you" in that question is always Dr. Shapiro
15 herself; right?
16 MR. SPECTER: Yes, yes.
17 THE WITNESS: I don't remember.
18 BY MR. SPECTER:
19 Q. Now, with respect to the
20 meta-analysis, was there a change in what endpoints
21 were looked at as the defined endpoints?
22 MR. MAYER: Are you asking about a
23 particular period of time?
24 MR. SPECTER: I'm asking about the
25 meta-analysis.

643
1 BY MR. SPECTER:
2 Q. Do you follow my question, Dr.
3 Shapiro?
4 A. Not exactly. We -- well, I guess I'm
5 assuming the one that we submitted to the FDA and
6 ones that we presented to the consultants. I mean,
7 I don't know what you are talking about.
8 Q. Yes. I'm talking about the
9 meta-analysis that you presented to FDA.
10 A. We never changed the primary
11 endpoint. We had decided before we conducted the
12 pooled analysis that we would use the APTC endpoint
13 as the endpoint for that.
14 Q. When was that decided, Doctor?
15 A. I don't know the exact month, but
16 after we sent out various information to consultants
17 and conferred with them, conferred with our in-house
18 cardiologists, they all gave us the same feedback,
19 that that was the appropriate endpoint to use for
20 further analyses.
21 Q. Well, the CV adjudication plan from
22 December '99 and January of 2000 defined the
23 endpoint as cardiovascular thrombotic events;
24 correct?
25 A. Well, it had many names. At

644
1 different times it was thromboembolic and thrombotic
2 and so on. There was a list of events that were
3 part of that endpoint, but when the consultants saw
4 that list, they said, you know, it doesn't coincide
5 with what's being used in the literature, what's
6 being used by the anti-platelet trialist and,
7 therefore, it is not easy to compare your results to
8 what's published in the literature. They preferred
9 that we use this external standard.
10 Q. Do you have some document that
11 demonstrates that your outside consultants told you
12 to do that?
13 A. I don't personally.
14 Q. Have you seen some document that says
15 that?
16 A. I don't recall. I recall being at
17 the meetings where it was discussed though.
18 Q. The APTC endpoint was not the
19 endpoint in the Merck SOP, standard operating
20 procedure, as it existed in late '99/early 2000;
21 correct?
22 MR. MAYER: I think she just answered
23 that question, but you can answer again, Dr.
24 Shapiro.
25 THE WITNESS: That's right.

645
1 BY MR. SPECTER:
2 Q. I'm correct; is that right?
3 A. Yes.
4 Q. And there was significant discussion
5 at Merck as to whether to use the Merck SOP that was
6 already in existence or to change it to the APTC
7 definition; correct?
8 MR. MAYER: Objection to the form.
9 THE WITNESS: I don't know that there
10 was significant discussion. There was a discussion
11 about it and a decision made.
12 BY MR. SPECTER:
13 Q. And --
14 A. There's a great deal of overlap, and
15 results from analyses of both endpoints are
16 consistent.
17 Q. It would be wrong if you chose one of
18 these endpoints over the other based upon what works
19 in Merck's favor; correct?
20 MR. MAYER: Objection to form. You
21 may answer.
22 THE WITNESS: We don't do that at
23 Merck. We choose what is most scientifically valid,
24 and we do that. And it was the judgment of the
25 experts that this was the best endpoint to use, and

646
1 we prespecified it before anyone saw the results of
2 the analysis, and that's the endpoint we used.
3 BY MR. SPECTER:
4 Q. Okay. Well, let's talk about what we
5 do or don't do at Merck, Dr. Shapiro.
6 MR. SPECTER: Marking Shapiro-52.
7 I'll give you a copy, I'll give a copy to your
8 lawyer.
9 - - -
10 (Whereupon, Deposition Exhibit
11 Shapiro-52, "Issues for the COXIB
12 Cardiovascular Combined Analyses and
13 Planned Interim PreVIGOR ACM
14 'meta-analysis,'" MRK-NJ0363443 -
15 MRK-NJ0363445, was marked for
16 identification.)
17 - - -
18 BY MR. SPECTER:
19 Q. Do you recognize this document?
20 A. No. I need to look at it.
21 (Witness reviewing document.)
22 Q. Do you recognize the document,
23 Doctor?
24 A. No.
25 Q. Okay. This is from Dr. Reicin's

647
1 custodial file. You know her, of course?
2 A. Yes.
3 Q. And you worked with her closely on
4 the issue we're currently discussing as well as many
5 other issues; correct?
6 A. Yes.
7 Q. And this document has your name in it
8 in quite a few places; is that correct?
9 A. Yes.
10 Q. This document concerns the issue
11 we're discussing, which was the internal discussion
12 at Merck concerning whether to use the SOP that was
13 already in place or to use the APTC option; correct?
14 A. Yes. It talks about the different
15 options.
16 Q. Right.
17 In discussing the pros and cons of
18 using the APTC option, it is written at the top of
19 Page 3 that the APTC option, looking at the very
20 top, "Includes 'bleeding' endpoints which mixes
21 risk/benefit (could be seen as a pro since this
22 could work in our favor)."
23 Did I read that correctly?
24 A. Yes.
25 Q. And the word "our" there refers to

648
1 Merck; correct?
2 A. Yes. I'd like to make a comment
3 about this point.
4 Q. Well, when I'm finished my questions,
5 Dr. Shapiro, and your lawyer has a chance to
6 question you, you can make whatever comment you'd
7 like.
8 Now, a major point of doing a
9 meta-analysis in the first place is to increase the
10 power to see if there is a statistically significant
11 increase in events; is that correct?
12 MR. MAYER: Object to the form.
13 THE WITNESS: I'm sorry. Can you
14 repeat the beginning?
15 BY MR. SPECTER:
16 Q. A point of doing, a major point, a
17 major reason for doing a meta-analysis is to
18 increase the power to see if there is a
19 statistically significant increase in events; is
20 that correct?
21 A. You definitely want to gather more
22 data to increase your power. That doesn't
23 necessarily mean that an endpoint that includes more
24 events is the right one to do, but, yes, the point
25 is to increase power and to gather all the data so

649
1 that you see the entire picture and not a partial
2 picture.
3 Q. When we talk about "power" in that
4 context, what is the definition of "power" in that
5 context?
6 A. It's the ability to detect a true
7 effect if one exists.
8 Q. And you're expert in that area; is
9 that correct?
10 MR. MAYER: Objection to form.
11 THE WITNESS: I'm trained certainly
12 in that area.
13 BY MR. SPECTER:
14 Q. And that is part of statistics; is
15 that correct?
16 A. Yes.
17 Q. And you're an expert in that field;
18 is that right?
19 A. Yes.
20 Q. And the endpoint that you chose was
21 not the endpoint that was prespecified in Merck's
22 own CV adjudication SOP; correct?
23 A. Yes.
24 Q. And it was not the one that would
25 give you the most power; correct?

650
1 MR. MAYER: Object to the form.
2 THE WITNESS: That's actually not
3 necessarily true at all. If you have an endpoint
4 that's not truly addressing whatever mechanism is at
5 work and is mixing things in that wouldn't be
6 affected by the mechanism, you can easily mask a
7 true effect by mixing in something that you are not
8 affecting, and especially if there's a lot of those
9 things you are not affecting, you will mask it
10 completely. So, no, just having more events does
11 not necessarily provide more power for you.
12 BY MR. SPECTER:
13 Q. And there would be more power if you
14 had used the CV thrombotic endpoint already
15 prespecified in your program-wide CV adjudication
16 plan?
17 A. I disagree.
18 Q. Correct?
19 A. No, that's not correct.
20 Q. Doctor, wasn't the driving force MIs
21 for the CV events in the meta-analysis?
22 MR. MAYER: Object to the form.
23 THE WITNESS: The -- as we stated
24 ourselves in the document to the FDA, the main event
25 driving the difference with naproxen was MIs.

651
1 BY MR. SPECTER:
2 Q. And in point of fact, this PowerPoint
3 that you told us a few minutes ago you looked at it
4 in preparing for today's deposition, that evaluated
5 and analyzed specifically MIs; is that correct?
6 MR. MAYER: Object to the form.
7 THE WITNESS: There were several
8 analyses presented in that document. One of them
9 was an analysis of MIs, but there are other
10 endpoints analyzed in it as well.
11 MR. SPECTER: And we'll mark that as
12 Shapiro-53.
13 - - -
14 (Whereupon, Deposition Exhibit
15 Shapiro-53, "Vioxx Preliminary
16 Cardiovascular Meta-Analysis Dr. Deborah
17 Shapiro October 18, 2000," Slide Set,
18 MRK-NJ0070364 - MRK-NJ0070397, was
19 marked for identification.)
20 - - -
21 BY MR. SPECTER:
22 Q. Is that the document that you were
23 just talking about, Doctor?
24 MR. MAYER: That's the document you
25 just asked her about.

652
1 BY MR. SPECTER:
2 Q. Is that correct?
3 A. Yes.
4 Q. Turning to the slide, this would have
5 been the slide, correct, originally?
6 A. Yes.
7 Q. Three from the back --
8 MR. MAYER: What's the Bates Number
9 or the last three digits of the Bates Number?
10 MR. SPECTER: 395.
11 BY MR. SPECTER:
12 Q. And that says, "MI Endpoint-Vioxx
13 versus NSAIDs." Correct?
14 A. Yes.
15 Q. And with a heart attack as the
16 endpoint among all patients, there were 46 heart
17 attacks in people taking Vioxx and 17 in people
18 taking other nonsteroidal anti-inflammatories;
19 correct?
20 A. Yes. There's a couple of problems
21 with that summary. One is there's fewer patient
22 years on NSAIDs. But the other more important
23 one --
24 Q. I'll get to that. I'm just talking
25 about what the numbers say.

653
1 A. Fine.
2 Q. Is that correct?
3 A. Uh-huh.
4 Q. The next thing is patient years;
5 correct?
6 A. Yes.
7 Q. And the comparison of patient years
8 was 6559 for Vioxx and 4728 for the other NSAIDs;
9 correct?
10 A. Yes.
11 Q. And the rate was .70 for people
12 taking Vioxx and .36 for people taking other NSAIDs;
13 correct?
14 A. Yes.
15 Q. And the relative risk was 2.02;
16 correct?
17 A. Yes. And it's not a legitimate
18 summary.
19 Q. It's your summary, isn't it?
20 A. Yes, it's my summary, but it is not
21 in context. If you look at the next page, it tells
22 you why that's not a legitimate summary. It's
23 provided and then explained. You cannot combine all
24 the trials, because there's a highly significant
25 difference between the naproxen trials and the

654
1 non-naproxen trials that are included in that
2 estimate. When that's the case, it is not an
3 appropriate summary statistic. So, while it's
4 presented for information, it's also, and as I
5 presented at the time, an inappropriate summary
6 statistic.
7 Q. Okay.
8 Well, I've heard you use the words
9 illegitimate and inappropriate to describe what you
10 did here. Would you tell me if those words,
11 illegitimate or inappropriate, appear anywhere on
12 this document?
13 MR. MAYER: Objection to the form.
14 She didn't describe what she did as illegitimate.
15 BY MR. SPECTER:
16 Q. You used the words illegitimate and
17 inappropriate to describe --
18 A. I would have to have it read back. I
19 didn't hear that, but it is not an appropriate
20 summary statistic to describe the data. This is a
21 power --
22 Q. My current question, Doctor, is, does
23 the word "illegitimate" appear anywhere in the
24 document?
25 A. It is implied by the bullet.

655
1 Q. So, the answer to my question is no;
2 is that correct?
3 A. This is a PowerPoint presentation.
4 Q. The current question is, does the
5 word illegitimate appear anywhere?
6 MR. MAYER: You have got to let her
7 finish her answer, Mr. Specter.
8 MR. SPECTER: I would like to hear --
9 MR. MAYER: Let her answer --
10 MR. SPECTER: I would like to a
11 direct answer to a direct question.
12 BY MR. SPECTER:
13 Q. Does the word "illegitimate" appear
14 anywhere? The question can be answered yes or no.
15 MR. MAYER: You can answer the
16 question as you wish, Dr. Shapiro, and Mr. Specter
17 can then ask another question.
18 THE WITNESS: While that word does
19 not appear, this is a PowerPoint presentation meant
20 to be brief and with bullets. There was
21 explanations that went along with it for the
22 audience that it was presented to. This isn't a
23 report where more details are provided, it is a
24 presentation.
25 The implication of the bullet that

656
1 says, "Significant difference between naproxen
2 versus other NSAID trials; p = 0.003," for someone
3 who understands the statistics, that invalidates
4 that summary statistic of 2.02.
5 BY MR. SPECTER:
6 Q. Does the word "inappropriate" appear
7 anywhere, Dr. Shapiro?
8 A. As I've already stated, it doesn't
9 appear, it is implied.
10 Q. And if you go down this list of
11 comparing the data on MI endpoints, the relative
12 risk in VIGOR, in ADVANTAGE, in RA, in non-RA, all
13 five of those have relative risks of 2.02, 5.0,
14 2.95, 1.82 and 1.68 respectively; is that correct?
15 MR. MAYER: Object to the form.
16 THE WITNESS: Almost all of the ones
17 you cited are naproxen trials, and naproxen is
18 different than non-naproxen. One would expect that
19 kind of a relative risk in the naproxen trials. It
20 is not present in the non-naproxen trials.
21 BY MR. SPECTER:
22 Q. I see.
23 Is the "nonRA" a naproxen trial?
24 A. It can be a mixture. I'm not sure
25 what "nonRA" is, but "RA" was naproxen.

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1 Q. That's my point. Do you know whether
2 "nonRA" involves naproxen?
3 A. I believe it's a mixture, but that's
4 why we changed the blocking, on the advice of the
5 consultants at this meeting. This blocking is not
6 an efficient way of looking at the data, and it is
7 not the blocking that ended up in the meta-analysis
8 that we submitted to the FDA.
9 At this meeting, we were advised to
10 set up blocks that were RA, OA and other
11 indications, and to examine naproxen versus
12 non-naproxen comparators. So, this blocking is not
13 an efficient, effective way of looking at the data.
14 Q. Doctor --
15 A. But you can tell that VIGOR was
16 naproxen, ADVANTAGE was naproxen, I believe RA was
17 all naproxen. NonRA can be a mixture. I don't know
18 what it is, I'd have to see the data again. It's a
19 long time.
20 Q. Dr. Shapiro, did you give this chart
21 to the FDA?
22 A. Not in this form, no. We --
23 Q. Did you give the FDA this MI endpoint
24 chart?
25 A. We gave the FDA all the MI

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1 information in each of the trials. It's contained
2 in the document that we sent to the FDA. All the MI
3 information is in there.
4 Q. But not as a specific myocardial
5 infarction endpoint; correct?
6 A. I disagree. The tables that we
7 provided to the FDA had myocardial infarction as one
8 of the many events they could break out separately.
9 It's all contained in the report we gave them.
10 Q. And this specific chart was not given
11 to FDA; correct?
12 MR. MAYER: Asked and answered. You
13 may answer it again.
14 BY MR. SPECTER:
15 Q. Is that correct, Doctor?
16 A. This specific chart was not given to
17 them.