IAN MCKEAGUE, PH.D
`MYLAN PHARMACEUTICALS INC. VS BIOGEN MA INC.
`
`April 24, 2019
`1
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`_____________________________ x
`
`MYLAN PHARMACEUTICALS INC.,
`
`IPR2018—01403
`
`Petitioner,
`
`Patent No. 8,399,514
`
`v.
`
`BIOGEN MA INC.,
`
`Patent Owner.
`
`_____________________________ x
`
`VIDEOTAPED DEPOSITION OF
`
`IAN MCKEAGUE, Ph.D.
`
`Wednesday, April 24, 2019
`
`TRANSCRIPT of deposition testimony as taken by
`
`and before MONIQUE VOUTHOURIS, a Certified Court
`
`Reporter, RPR, CRR, Realtime Systems Administrator, and
`
`Notary Public of the State of New York, at the offices
`
`of PERKINS COIE, 30 Rockefeller Plaza, New York, New
`
`York, 10112, on Wednesday, April 24, 2019, commencing
`
`at 9:01 a.m.
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`Biogen Exhibit 2064
`
`Mylan v. Biogen
`IPR 2018-01403
`
`
`
`9 Q
`=4 ES QIOBUE
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`Page 1 of 141
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`800.211.DEPO (3376
`EsquireSo/utions.con21
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`MYLAN PHARMACEUTICALS INC. VS BIOGEN MA INC.
`
`April 24, 2019
`1
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`_____________________________ x
`
`MYLAN PHARMACEUTICALS INC.,
`
`IPR2018—01403
`
`Petitioner,
`
`Patent No. 8,399,514
`
`v.
`
`BIOGEN MA INC.,
`
`Patent Owner.
`
`_____________________________ x
`
`VIDEOTAPED DEPOSITION OF
`
`IAN MCKEAGUE, Ph.D.
`
`Wednesday, April 24, 2019
`
`TRANSCRIPT of deposition testimony as taken by
`
`and before MONIQUE VOUTHOURIS, a Certified Court
`
`Reporter, RPR, CRR, Realtime Systems Administrator, and
`
`Notary Public of the State of New York, at the offices
`
`of PERKINS COIE, 30 Rockefeller Plaza, New York, New
`
`York, 10112, on Wednesday, April 24, 2019, commencing
`
`at 9:01 a.m.
`
`Biogen Exhibit 2064
`
`Mylan v. Biogen
`IPR 2018-01403
`
`
`
`9 Q
`=4 ES QIOBUE
`
`Page 1 of 141
`
`800.211.DEPO (3376
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
`
`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
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`April 24, 2019April 24, 20192
`
`1 APPEARANCES OF COUNSEL
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`2 ON BEHALF OF PETITIONER MYLAN PHARMACEUTICALS INC.
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`3 AND THE WITNESS, IAN MCKEAGUE, Ph.D.:
`
`4 PERKINS COIE
` 33 East Main Street
`5 Suite 201
` Madison, Wisconsin
`6 608.772.4250
` BY:
`DAVID L. ANSTAETT, ESQ.
`7 danstaett@perkinscoie.com
`
`53703-3095
`
`8 PERKINS COIE
` 1888 Century Park East
`9 Suite 1700
` Los Angeles, California
`10 310.788.9900
` BY:
`COURTNEY M. PROCHNOW, Ph.D., ESQ.
`11 cprochnow@perkinscoie.com
`
`90067-1721
`
`12
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`13
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`ON BEHALF OF PATENT OWNER BIOGEN MA INC.:
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`14 FINNEGAN, HENDERSON, FARABOW, GARRETT &
` DUNNER, LLP
`15 901 New York Avenue, NW
` Washington, DC
`20001-4413
`16 202.408.4000
` BY:
`MARK J. FELDSTEIN, Ph.D.,, ESQ.
`17 mark.feldstein@finnegan.com
` -and-
`18 MICHAEL R. GALGANO, ESQ.
` michael.galgano@finnegan.com
`19
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`20
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`21
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`ALSO PRESENT:
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`22 MARCELLO RIVERA, Legal Video Specialist
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`23
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`24
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`25
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`800.211.DEPO (3376)800.211.DEPO (3376)
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`EsquireSolutions.comEsquireSolutions.com
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
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`1 INDEX
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`
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`April 24, 2019April 24, 20193
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`2 WITNESS PAGE
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`3 IAN MCKEAGUE, Ph.D.
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`4 Examination by Mr. Feldstein........................6
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`5 ......................139
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`6 Examination by Mr. Anstaett.......................137
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` EXHIBITS
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`7 8 9
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`10
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`DEPOSITION EXHIBIT PAGE
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`11 Exhibit 2051 Article from Statistics in
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`12 Medicine 2003...........................6
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`13
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`14
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`MYLAN PHARMS. INC. PREVIOUSLY MARKED EXHIBITS PAGE
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`15 Exhibit 1004 Declaration of Ian McKeague, Ph.D.
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`16 in Support of Petition for Inter
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`17 Partes Review of U.S. Patent
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`18 No. 8,399,514...........................6
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`19 Exhibit 1007 Document "Sixteenth Meeting of the
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`20 European Neurological Society 27-31
`
`21 May 2006, Lausanne, Switzerland."......43
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`22 Exhibit 1036 Document "Multiple Sclerosis
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`23 Therapeutics Fourth Edition............55
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`24 Exhibit 1037 European Medicines Agency Assessment
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`25 report 26 November 2013 Tecfidera.....109
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
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`
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`April 24, 2019April 24, 20194
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`1 MYLAN PHARMS. INC. PREVIOUSLY MARKED EXHIBITS PAGE
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`2 Exhibit 1038 New England Journal of Medicine
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`3 article "Placebo-Controlled Phase 3
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`4 Study of Oral BG-12 for Relapsing
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`5 Multiple Sclerosis....................117
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`6 Exhibit 1039 New England Journal of Medicine
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`7 article "Placebo-Controlled Phase 3
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`8 Study of Oral BG-12 or Glatiramer in
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`9 Multiple Sclerosis."..................117
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`10 Exhibit 1048 Article "Efficacy and safety of oral
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`11 fumarate in patients with
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`12 relapsing-remitting multiple
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`13 sclerosis: A multicentre, randomised,
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`14 double-blind, placebo-controlled
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`15 phase IIb study.".....................137
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`16
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`17
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`18
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`19
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`20
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`21
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`22
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`23
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`24
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`25
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
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`April 24, 2019April 24, 20195
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`1 THE VIDEOGRAPHER: This is the digitized video
`
`09:01:18
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`2 deposition of Dr. Ian McKeague in the matter Mylan
`
`3 Pharmaceuticals Inc. versus Biogen MA Inc. This
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`09:01:20
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`09:01:27
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`4 deposition is being held at the law offices of Perkins
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`09:01:30
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`5 Coie located at 30 Rockefeller Plaza, New York, New
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`6 York, on April 24th, 2019, at approximately 9 a.m.
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`7 My name is Marcello Rivera from Esquire
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`8 Solutions and I am the legal video specialist. The
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`09:01:34
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`09:01:37
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`09:01:41
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`09:01:44
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`9 court reporter is Monique Vouthouris in association with
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`09:01:49
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`10 Esquire Solutions.
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`11 Will present counsel please introduce
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`12 themselves for the record.
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`09:01:51
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`09:01:53
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`09:01:55
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`13 MR. FELDSTEIN: This is Mark Feldstein from
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`09:01:56
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`14
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`Finnegan Henderson on behalf of the Patent Owner Biogen.
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`09:01:58
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`15
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`With me today is Mike Galgano, also from Finnegan
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`16
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`Henderson.
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`09:02:02
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`09:02:05
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`17 MR. ANSTAETT: David Anstaett of Perkins Coie
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`09:02:05
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`18
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`on behalf of the witness and Petitioner Mylan
`
`19 Pharmaceuticals, Inc. With me today is Courtney
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`20
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`Prochnow, also of Perkins Coie.
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`09:02:09
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`09:02:11
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`09:02:13
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`21 THE VIDEOGRAPHER: Will the court reporter
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`09:02:17
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`22 please swear in the witness.
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`23 I A N M C K E A G U E,
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`24
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`having been first duly sworn by the Notary,
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`25 testifies as follows:
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`09:02:18
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`09:02:32
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`09:02:32
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`09:02:32
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`1 EXAMINATION BY MR. FELDSTEIN:
`
`
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`April 24, 2019April 24, 20196
`
`2 Q. Good morning, Doctor. How are you?
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`3 A. Fine, thank you.
`
`4 Q. Good. I've already handed you your
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`09:02:44
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`09:02:44
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`09:02:46
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`09:02:47
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`5 declaration, Exhibit 1004. Do you have that in front of
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`09:02:50
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`6 you?
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`7 A. I do.
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`8 Q. Or maybe you brought that. I don't know.
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`9 A. Yes.
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`09:02:52
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`09:02:52
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`09:02:53
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`09:02:55
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`10 MR. ANSTAETT: He brought that, but I don't
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`09:02:55
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`11
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`know if it's got the -- it's got the exhibit number on
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`09:02:57
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`12 it, I believe.
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`13 A. It's got the exhibit.
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`09:02:59
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`09:03:00
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`14 Q. Okay. Terrific. And before we go into that,
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`09:03:01
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`15
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`but I'm glad you have it, I want to mark one of your own
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`09:03:06
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`16
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`pieces of research.
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`09:03:12
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`17 MR. FELDSTEIN: I'm going to mark as Exhibit
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`09:03:14
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`18
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`2051 an article from Statistics in Medicine 2003, first
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`09:03:16
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`19 author is Gilbert.
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`20 (Exhibit 2051, Article from Statistics in
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`21
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`Medicine 2003, marked for identification.)
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`22 Q. Is Exhibit 2051 an article that you
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`23
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`co-authored, Doctor?
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`24 A. Um-hmm, indeed I did.
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`09:03:23
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`09:03:31
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`09:03:31
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`09:03:31
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`09:03:33
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`09:03:34
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`25 Q. I just want to use this as a teeing-off point
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`09:03:35
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
`
`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
`
`April 24, 2019April 24, 20197
`
`1 for some background questions. This is titled that it's
`
`09:03:40
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`2 a cohort study?
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`3 A. That's correct.
`
`4 Q. Can you explain what a cohort study is?
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`5 A. A cohort study is where you -- it's a
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`09:03:44
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`09:03:45
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`09:03:46
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`09:03:48
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`6 longitudinal study where individuals are followed and
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`09:03:52
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`7 studied longitudinally, essentially.
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`8 Q. And how, if at all, does a cohort study
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`09:03:55
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`09:03:59
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`9 differ from a phase I or a phase II or a phase III drug
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`09:04:04
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`10 trial?
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`11 MR. ANSTAETT: Objection; form.
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`12 You can answer.
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`09:04:07
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`09:04:07
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`09:04:09
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`13 A. So the question is how does a cohort study
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`09:04:09
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`14 differ from a phase I, phase II --
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`15 Q. Or phase III drug trial.
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`09:04:13
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`09:04:17
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`16 A. -- or phase III drug trial? Cohort studies
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`09:04:19
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`17 are typically used in epidemiology, and I've worked
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`09:04:23
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`18
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`extensively in epidemiology where the kind of studies
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`09:04:27
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`19 are typically observational, so we collect observational
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`09:04:31
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`20
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`data on subjects.
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`09:04:34
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`21 Phase II, phase III studies are randomized,
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`09:04:36
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`22 randomized studies. We have the luxury of randomly
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`23
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`assigning subjects to treatment groups.
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`24 Q. Are there any other differences between
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`09:04:40
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`09:04:46
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`09:04:48
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`25 cohort studies, as you used the term, and the phase II,
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`09:04:51
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`1 for example, trial for FDA approval?
`
`2 A. Well --
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`3 MR. ANSTAETT: Objection to form.
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`4 You can answer.
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`5 A. So any other differences?
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`6 Q. Yes.
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`
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`April 24, 2019April 24, 20198
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`09:04:55
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`09:04:57
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`09:04:57
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`09:04:59
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`09:05:01
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`09:05:02
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`7 A. Well, there are -- there are -- yeah, there
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`09:05:03
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`8 are scientific differences indeed, yes, in how the --
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`09:05:07
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`9 how the data are analyzed, assumptions that come into
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`09:05:11
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`10 the -- the analysis --
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`11 Q. And can you give -- I'm sorry.
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`12 Can you give any examples of those
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`13
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`differences?
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`09:05:14
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`09:05:15
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`09:05:17
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`09:05:18
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`14 A. Well, that's a very broad question, right.
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`09:05:19
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`15
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`So statistics -- do you mean from a statistical point of
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`09:05:22
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`16
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`view? Do you mean from an epidemiological point of
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`17 view?
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`Or -- or a design point of view?
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`18 Q. Let's start with --
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`19 A. It's a very broad question.
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`09:05:27
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`09:05:30
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`09:05:30
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`09:05:33
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`20 Q. Let's start with the design point of view as
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`09:05:34
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`21
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`it relates then to the statistical analysis.
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`22 A. The design point of view. So, well, as I
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`23
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`said, randomized trials have a different design from
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`24 cohort -- cohort design because cohort studies are
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`09:05:37
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`09:05:40
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`09:05:43
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`09:05:48
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`25 observational. So there is no random assignment to --
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`09:05:55
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
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`April 24, 2019April 24, 20199
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`1 to treatment groups, say. I've already said that.
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`2 Q. Okay. Any other examples of differences?
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`3 A. Well, that's the --
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`4 MR. ANSTAETT: Objection to form.
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`5 A. So, well, that's the key difference, of
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`6 course.
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`7 Q. Okay.
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`8 A. But there are -- there are, of course,
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`9 differences, yeah, there are many differences, as I
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`09:05:58
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`09:06:02
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`09:06:04
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`09:06:04
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`09:06:09
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`09:06:09
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`09:06:10
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`09:06:11
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`10 said. I'm not giving you the lecture on cohort studies
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`09:06:14
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`11 or cohort design or -- or randomized designs. But
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`12
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`that's the key difference.
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`09:06:19
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`09:06:23
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`13 Q. Did the cohort studies that you've worked on
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`09:06:24
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`14 involve administration of a drug?
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`09:06:28
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`15 A. The cohort -- generally the cohort studies?
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`09:06:30
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`16
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`Yes, indeed, I've involved with -- I've been involved
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`09:06:36
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`17 with cohort studies involving drugs, yes.
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`09:06:40
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`18 Q. Where the drug is administered you're saying
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`09:06:42
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`19 to the patient and then followed for results?
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`09:06:47
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`20 A. Well, for example, I -- in recent years I've
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`09:06:49
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`21
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`worked with SSRI, which is a treatment for depression,
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`09:06:51
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`22 and I studied data from Finland on the administration of
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`09:06:56
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`23
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`SSRI during pregnancy, pregnant women, understanding the
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`09:07:01
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`24 effects of that on the offspring, the -- the children
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`09:07:05
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`25 born from these mothers who -- who had depression, but
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`09:07:08
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
`
`April 24, 2019April 24, 201910
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`1 also had SSRIs.
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`2 Q. Right. And in that -- in that --
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`09:07:13
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`09:07:15
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`3 A. That's observational, that's an observational
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`09:07:17
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`4 study.
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`It's not a -- we didn't randomly assign SSRI
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`09:07:20
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`5 drugs to women or -- or not. So that's -- that's the --
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`09:07:24
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`6 that's the key difference. That's a cohort study.
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`09:07:28
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`7 Q. Right. In that -- in that SSRI study, the
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`09:07:30
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`8 subjects already had or didn't already have SSRI
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`9 administered, there was no administering of an SSRI
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`10 under the protocol call of the design. Correct?
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`09:07:35
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`09:07:39
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`09:07:42
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`11 A. So this was not a -- this was not a -- so the
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`09:07:45
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`12 design of the study was essentially retrospective, so we
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`09:07:49
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`13
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`already had the data, right. We didn't -- we didn't
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`09:07:53
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`14 prospectively assign women to take SSRIs or not. We had
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`09:07:56
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`15 -- it was just, as I say, purely observational. We had
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`09:08:02
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`16 -- we had data from clinics in Finland about SSRI use
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`09:08:06
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`17 during pregnancy and we were mining that -- mining that
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`09:08:10
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`18
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`data to -- to try and understand the epidemiology of --
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`09:08:13
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`19 of SSRI administration during pregnancy.
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`09:08:17
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`20 Q. And so the cohort studies, they don't tend to
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`09:08:20
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`21
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`involve prospective administration of a drug in
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`22 following the patient after administration. Is that
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`23 correct?
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`24 MR. ANSTAETT: Object --
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`25 A. That's a general --
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`09:08:24
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`09:08:29
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`09:08:29
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`09:08:29
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`09:08:32
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
`
`April 24, 2019April 24, 201911
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`1 MR. ANSTAETT: Objection to form.
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`2 A. That's the general --
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`09:08:32
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`09:08:32
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`3 MR. ANSTAETT: Dr. McKeague, sorry, you've
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`09:08:34
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`4 just got to give me a chance to lodge my objections on
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`09:08:35
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`5 the record.
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`6 Objection to form.
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`7 A. So -- so your question was, again?
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`09:08:39
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`09:08:40
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`09:08:40
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`8 Q. The cohort studies, such as that SSRI study,
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`09:08:43
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`9 it didn't involve prospectively administering a drug to
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`09:08:47
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`10
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`the patient and then following the patient. Correct?
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`09:08:52
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`11 MR. ANSTAETT: Objection to form.
`
`12 You can answer.
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`13 A. Well, it was a retrospective analysis of
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`14
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`the -- the women, of course, had been -- went to a
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`09:08:54
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`09:08:55
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`09:08:56
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`09:09:04
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`15 physician, they had depression, they were given an SSRI
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`09:09:08
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`16 drug. But we -- we weren't privy to that in a
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`17
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`prospective fashion.
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`09:09:12
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`09:09:15
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`18 This was a retrospective analysis, as I just
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`09:09:16
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`19
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`explained to you, it was a retrospective analysis based
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`09:09:19
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`20 on -- based on such information and then follow-up with
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`09:09:24
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`21 the children, and the follow-up, it's -- right now it's
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`09:09:27
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`22
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`in the late teenage years of the children, of the
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`23 offspring.
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`24 Q. Right.
`
`25 A. So we have, of course -- we're having
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`09:09:29
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`09:09:33
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`09:09:33
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`09:09:33
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`April 24, 2019April 24, 201912
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`1 prospective follow-up of children because there is
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`09:09:36
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`2 more -- their -- their data, of course, are continuing,
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`09:09:40
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`3 we're -- we're studying psychiatric outcomes for these
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`09:09:43
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`4 children, whether they -- whether it be autism,
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`5 schizophrenia, various psychiatric outcomes.
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`09:09:46
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`09:09:52
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`6 Q. So maybe my question wasn't well-formed. But
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`09:09:54
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`7 do you understand I was asking about prospectively
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`8 administering a drug as opposed to what you're
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`09:09:58
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`09:10:01
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`9 describing now is prospectively following the children?
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`09:10:03
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`10 MR. ANSTAETT: Objection to form.
`
`11 A. Was that a question?
`
`12 Q. My prior question was the cohort studies,
`
`13
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`such as the SSRI study, didn't involve prospectively
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`09:10:06
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`09:10:07
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`09:10:09
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`09:10:13
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`14 administering a drug to the patient and then following
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`09:10:17
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`15
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`the patient. Correct?
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`16 MR. ANSTAETT: Objection to form.
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`09:10:20
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`09:10:21
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`17 A. So as I explained -- well, I explained how we
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`09:10:24
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`18
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`got the data, right? Didn't that answer your question?
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`09:10:29
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`19 Q. No, I'm not asking about the data. I'm
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`09:10:31
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`20
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`asking about the administering of the drug. Let me --
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`09:10:34
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`21 let me try it a different way.
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`09:10:35
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`22 In a phase II trial the patient comes in to
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`09:10:37
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`23
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`the study, the study design includes the patient coming
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`09:10:40
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`24 in, being administered a drug as part of the protocol,
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`09:10:43
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`25 and then following somebody, generally, right?
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`09:10:47
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`April 24, 2019April 24, 201913
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`1 A. Indeed.
`
`2 Q. And in your cohort studies, like the SSRI
`
`3 study, the patient before they -- before you -- the
`
`4 study was designed already did or didn't have SSRI
`
`5 administered. Correct?
`
`6 MR. ANSTAETT: Objection to form.
`
`09:10:50
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`09:10:50
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`09:10:54
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`09:10:58
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`09:11:01
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`09:11:02
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`7 A. So as -- I thought I explained the SSRI study
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`09:11:04
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`8 pretty clearly, didn't I?
`
`9 So we had data on -- on pregnant women in
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`10 databases in Finland. We know whether they were
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`09:11:08
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`09:11:10
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`09:11:14
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`11
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`administered SSRI during their pregnancy. That is --
`
`09:11:17
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`12 that is retrospective data, right, because we go into
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`09:11:22
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`13
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`the medical record data in Finland and get that, get
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`14 those records.
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`09:11:26
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`09:11:29
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`15 Q. So I appreciate that you continue to explain,
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`09:11:30
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`16
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`but are you agreeing or disagreeing with my question?
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`09:11:33
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`17 That's what I'm having trouble following.
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`18 MR. ANSTAETT: One second, Dr. McKeague.
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`19
`
`Objection to the form of the question; asked and
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`20
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`answered.
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`21 A. Sorry, didn't I answer the question?
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`09:11:37
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`09:11:39
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`09:11:41
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`09:11:43
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`09:11:43
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`22 Q. I'm asking correct, yes or no, the SSRI study
`
`09:11:45
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`23
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`designed entailed having patient data where the patients
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`09:11:51
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`24 already did or didn't have SSRI administered before the
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`09:11:56
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`25 study was designed. Correct?
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`09:12:00
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`April 24, 2019April 24, 201914
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`1 MR. ANSTAETT: Objection to form.
`
`09:12:02
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`2 A. I still don't -- it's a -- it's a misleading
`
`09:12:07
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`3 question because I told you how the study was designed,
`
`09:12:10
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`4 right?
`
`So...
`
`09:12:14
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`5 Q. So you can't -- it's a misleading question to
`
`09:12:16
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`6 ask whether before the study was designed the patients
`
`09:12:20
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`7 either did or didn't have SSRI administered?
`
`09:12:23
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`8 MR. ANSTAETT: Objection to the form of the
`
`09:12:27
`
`9 question; asked and answered.
`
`09:12:28
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`10 A. That is -- that -- that wasn't part of the
`
`09:12:29
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`11
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`design of the study, what your -- what your question is
`
`09:12:31
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`12 entailing.
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`09:12:33
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`13 Q. Is there something wrong with my question?
`
`09:12:34
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`14 Is there some reason you can't answer my question?
`
`15 MR. ANSTAETT: Objection to form.
`
`16 A. Well, I don't understand your question.
`
`17 Q. Okay.
`
`09:12:38
`
`09:12:40
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`09:12:40
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`09:12:40
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`18 MR. ANSTAETT: Asked and answered. Sorry.
`
`09:12:43
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`19 THE WITNESS: Sorry.
`
`20 Q. When was your SSRI cohort study designed,
`
`21
`
`roughly?
`
`22 A. So this -- this started about six, seven
`
`23
`
`years ago, um-hmm.
`
`24 Q. So 2012-ish?
`
`09:12:46
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`09:12:55
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`09:13:00
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`09:13:02
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`09:13:06
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`09:13:07
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`25 A. Yes, around about there, plus or minus a year
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`09:13:12
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`
`
`April 24, 2019April 24, 201915
`
`1 or so.
`
`09:13:15
`
`2 Q. The women whose -- who you're following in
`
`09:13:16
`
`3 that study, would they already have had SSRI
`
`4 administered or not prior to 2012?
`
`09:13:19
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`09:13:23
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`5 A. So the -- the women were not being followed.
`
`09:13:27
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`6 It was the children. I thought I explained that. The
`
`09:13:30
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`7 children were being followed.
`
`8 Q. Fine, the children of the mothers.
`
`9 A. Yes.
`
`10 Q. Right?
`
`11 A. The children of the mothers.
`
`09:13:33
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`09:13:34
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`09:13:37
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`09:13:37
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`09:13:38
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`12 Q. And the mothers by 2012 already did or didn't
`
`09:13:41
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`13
`
`have SSRI administered. Correct?
`
`14 A. Well, of course, they -- that kind of
`
`15
`
`information was frozen into the -- into the study
`
`16
`
`because we were only looking at mothers who at that
`
`09:13:44
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`09:13:47
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`09:13:51
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`09:13:53
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`17 point, the start of the study, had already had an SSRI
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`09:13:58
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`18
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`administered or not. Because some -- we looked at some
`
`09:14:02
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`19
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`mothers who just suffered from depression and may not
`
`09:14:05
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`20
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`have had SSRI, and some, of course, who didn't suffer
`
`09:14:09
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`21
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`from depression and, of course, didn't have SSRI. So
`
`09:14:14
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`22
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`there were -- there were three groups, basically, of
`
`09:14:17
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`23
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`women mined from records, hospital records in Finland --
`
`09:14:19
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`24 Q. And you were looking -- you were looking at
`
`09:14:23
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`25 their hospital records from prior to 2012 to categorize
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`09:14:24
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
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`April 24, 2019April 24, 201916
`
`1 them into whether they had taken SSRI or had not taken
`
`09:14:27
`
`2 SSRI or fell into your third category. Correct?
`
`3 A. Yes.
`
`4 Q. Okay. Thank you.
`
`5 In your article, Exhibit 2051 --
`
`6 A. Yes.
`
`7 Q. -- can you turn to page 584. There is a
`
`09:14:32
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`09:14:35
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`09:14:36
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`09:14:42
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`09:14:42
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`09:14:47
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`8 section 4.3, "Covariate-Adjusted Analyses." Do you see
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`09:14:59
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`9 that?
`
`10 A. Um-hmm, yes.
`
`11 Q. Can you explain generally what a
`
`12
`
`covariate-adjusted analysis is?
`
`09:15:03
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`09:15:03
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`09:15:03
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`09:15:07
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`13 A. So there may be outcome variables, but there
`
`09:15:09
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`14
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`are also other variables involved in the -- in the
`
`09:15:13
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`15 subjects that we're collecting data on. So sometimes
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`09:15:18
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`16
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`the -- the effects may be adjusted for covariate
`
`17
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`information.
`
`18 Q. And what is covariate?
`
`19 A. A covariate is just a variate, it's just
`
`09:15:21
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`09:15:25
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`09:15:25
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`09:15:28
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`20
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`another variable. But it's called a covariate because
`
`09:15:31
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`21
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`it -- it varies in conjunction with the other -- the
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`09:15:35
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`22
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`other -- the variables of interest, perhaps, or the
`
`23 outcome variables.
`
`09:15:38
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`09:15:40
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`24 Q. And so what's -- what does one do to do a
`
`09:15:41
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`25
`
`covariate analysis?
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`09:15:45
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`
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`April 24, 2019April 24, 201917
`
`1 A. That's a very broad question.
`
`09:15:46
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`2 Q. So just generally what does one do to do a
`
`09:15:50
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`3 covariate analysis?
`
`09:15:53
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`4 MR. ANSTAETT: Objection to the form of the
`
`09:15:55
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`5 question.
`
`09:15:57
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`6 A. That's -- that's -- that is about 50 percent
`
`09:15:57
`
`7 of what statisticians do.
`
`8 Q. Can you explain generally how one does a
`
`9 covariate analysis, Doctor?
`
`10 MR. ANSTAETT: Objection --
`
`09:15:59
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`09:16:01
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`09:16:04
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`09:16:05
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`11 A. Well, one develops a model, one analyzes the
`
`09:16:05
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`12 model for understanding the effects of covariates,
`
`09:16:09
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`13
`
`that's the -- that's the broad philosophy of statistics.
`
`09:16:13
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`14 Q. What kind of data is used for a covariate
`
`15
`
`analysis?
`
`16 MR. ANSTAETT: Objection to form.
`
`09:16:16
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`09:16:19
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`09:16:20
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`17 A. Yeah, data. Obviously, data on covariates,
`
`09:16:21
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`18
`
`as well as outcome variables.
`
`19 Q. And you --
`
`20 A. But there may be -- it's a very broad
`
`09:16:27
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`09:16:27
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`09:16:29
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`21
`
`question, because, indeed, there can be missingness of
`
`09:16:32
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`22 outcome variables of covariates that can be an
`
`09:16:35
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`23
`
`enormously complicated data structure that has to be --
`
`09:16:39
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`24 has to be modeled.
`
`09:16:43
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`25 Q. In the cohort studies it seems, having looked
`
`09:16:44
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
`
`April 24, 2019April 24, 201918
`
`1 through your papers, that covariate analyses are pretty
`
`09:16:49
`
`2 common in your cohort studies?
`
`3 MR. ANSTAETT: Objection to form.
`
`09:16:53
`
`09:16:55
`
`4 A. Pretty common in what -- what do you mean?
`
`09:16:56
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`5 In my papers or --
`
`6 Q. In your papers.
`
`09:16:58
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`09:16:59
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`7 A. I write very broadly. I don't know if you've
`
`09:17:01
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`8 looked at my CV, but I -- what is -- why has my research
`
`09:17:05
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`9 interests got to do with the -- your broader question,
`
`09:17:13
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`10 your broader question was what is the role of covariate
`
`09:17:17
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`11
`
`analysis, I think.
`
`12 Q. My question --
`
`09:17:22
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`09:17:22
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`13 A. You mean -- you mean my research interests,
`
`09:17:23
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`14 or in my research interests, or what --
`
`09:17:25
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`15 Q. Maybe we can read back the question for you,
`
`09:17:29
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`16
`
`Doctor.
`
`17 MR. FELDSTEIN: Can you read back the
`
`18
`
`question, please.
`
`19 (The following is read by the reporter:
`
`09:17:31
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`09:17:31
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`09:17:32
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`09:17:52
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`20 "QUESTION: In the cohort studies it seems,
`
`09:16:45
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`21
`
`having looked through your papers, that covariate
`
`22 analyses are pretty common in your cohort studies?")
`
`23 MR. ANSTAETT: Objection to form.
`
`09:16:48
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`09:16:51
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`09:17:53
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`24 A. Yes, I don't know what you mean by "pretty
`
`09:17:55
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`25 common."
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`09:17:58
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
`
`
`
`April 24, 2019April 24, 201919
`
`1 Q. Okay. How often do you use cohort -- excuse
`
`09:18:01
`
`2 me.
`
`09:18:04
`
`3 How often do you use covariate analyses in
`
`09:18:04
`
`4 your cohort studies?
`
`09:18:10
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`5 A. I have, for example, in recent -- recent work
`
`09:18:11
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`6 I have to do with empirical likelihood is a --
`
`7 (Reporter clarification.)
`
`09:18:15
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`09:18:15
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`8 A. Empirical likelihood is a research area which
`
`09:18:22
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`9 actually sometimes involves covariates, but rarely.
`
`10 That's a major research interest of mine.
`
`11 MR. FELDSTEIN: Can you read back the
`
`12
`
`question.
`
`09:18:24
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`09:18:28
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`09:18:37
`
`09:18:38
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`13 Q. Can you try to answer the question, please,
`
`09:18:39
`
`14 Doctor.
`
`15 A. I thought I did --
`
`16 MR. ANSTAETT: Wait, wait, I'm sorry.
`
`17
`
`Objection to form. Objection; argumentative.
`
`18 MR. FELDSTEIN: Can you read back the
`
`19
`
`question.
`
`20 (The following is read by the reporter:
`
`21 "QUESTION: Okay. How often do you use
`
`22 cohort -- excuse me.
`
`09:18:41
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`09:18:42
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`09:18:44
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`09:18:45
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`09:18:49
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`09:18:50
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`09:19:15
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`09:18:02
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`09:18:04
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`23 How often do you use covariate analyses in
`
`09:18:04
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`24 your cohort studies?")
`
`09:18:10
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`25 A. How often do I have covariates in my cohort
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`09:19:17
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`
`
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`April 24, 2019April 24, 201920
`
`1 studies is that? Or how often do I use?
`
`09:19:22
`
`2 Q. How often do you use covariate analyses in
`
`09:19:24
`
`3 your cohort studies?
`
`4 MR. ANSTAETT: Objection to form.
`
`09:19:28
`
`09:19:29
`
`5 A. When -- so the simple answer is when it's
`
`09:19:30
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`6 called for, right.
`
`7 Q. That doesn't answer the question of how
`
`8 often, Doctor.
`
`9 A. How often --
`
`09:19:32
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`09:19:34
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`09:19:36
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`09:19:37
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`10 MR. ANSTAETT: You know what, objection to
`
`09:19:38
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`11
`
`form; argumentative, asked and answered.
`
`09:19:39
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`12 Q. Can you answer the question of how often you
`
`09:19:42
`
`13
`
`use covariate analyses in your cohort studies?
`
`14 MR. ANSTAETT: Same objection.
`
`09:19:45
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`09:19:48
`
`15 A. So I'd have to go through all my papers and
`
`09:19:49
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`16
`
`do a count.
`
`17 Q. You don't have --
`
`09:19:52
`
`09:19:54
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`18 A. I have -- I have -- I have about 150 papers,
`
`09:19:55
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`19
`
`so...
`
`09:19:58
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`20 Q. You don't have a rough idea in your head of
`
`09:19:58
`
`21
`
`how often you use covariate --
`
`09:20:01
`
`22 A. You mean percentage of papers where I have
`
`09:20:03
`
`23
`
`covariates?
`
`09:20:06
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`24 Q. You don't have an idea in your head, Doctor,
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`09:20:07
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`25
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`of roughly how often in your cohort studies you used
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`09:20:09
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`800.211.DEPO (3376)800.211.DEPO (3376)
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`EsquireSolutions.comEsquireSolutions.com
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`Page 20 of 141
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
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`
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`April 24, 2019April 24, 201921
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`1 covariate analysis --
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`2 MR. ANSTAETT: Objection to form.
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`09:20:13
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`09:20:13
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`3 A. You mean per paper or per data set? I mean,
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`09:20:14
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`4 your question is so vague that I can't answer it.
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`09:20:17
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`5 Q. You can answer it any of those ways you like.
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`09:20:20
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`6 Do you have any idea in your head, Doctor, of how often
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`09:20:23
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`7 your covariate -- excuse me.
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`09:20:25
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`8 Do you have any idea in your head, Doctor, of
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`09:20:26
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`9 how often in your cohort studies you use a covariate
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`10 analysis?
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`11 MR. ANSTAETT: Objection; form.
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`12 Q. If the answer is no, that's fine.
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`09:20:28
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`09:20:28
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`09:20:28
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`09:20:33
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`13 A. Sometimes -- you -- you pointed to an example
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`09:20:33
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`14 of where there is a covariate-adjusted analysis included
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`09:20:36
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`15
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`in this paper as a section, yes, so there is an example.
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`09:20:39
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`16
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`There are -- I can point to many, many papers of mine
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`09:20:42
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`17 where there is no -- there are no covariate analyses, in
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`09:20:45
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`18
`
`your words, whatever -- whatever you mean by that.
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`09:20:47
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`19 Q. Do you have an idea in your head, Doctor, of
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`09:20:51
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`20
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`how often in your cohort studies you used a covariate
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`09:20:54
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`21
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`analysis? Yes or no.
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`09:21:00
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`22 MR. ANSTAETT: Objection to form; asked and
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`09:21:01
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`23
`
`answered, argumentative.
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`24 A. So what we just talked about here is an
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`09:21:02
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`09:21:03
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`25 example and I -- I can give you numerous examples where
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`09:21:05
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`800.211.DEPO (3376)800.211.DEPO (3376)
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`EsquireSolutions.comEsquireSolutions.com
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`Page 21 of 141
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`IAN MCKEAGUE, PH.DIAN MCKEAGUE, PH.D
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`MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.MYLAN PHARMACEUTICALS INC. vs BIOGEN MA INC.
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`
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`April 24, 2019April 24, 201922
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`1 no covariate analysis
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