MOLNAR et al v. MERCK & CO., INC.
Filing
2567
OPINION filed (Civil Case No. 11-5304). Signed by Judge Joel A. Pisano on 4/10/2013. (eaj)
NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
:
IN RE: FOSAMAX (ALENDRONATE SODIUM) :
PRODUCTS LIABILITY LITIGATION
:
:
_________________________________________ :
:
BERNADETTE GLYNN and RICHARD GLYNN, :
:
Plaintiffs,
:
:
v.
:
:
MERCK SHARP & DOHME CORP,
:
:
Defendant.
:
:
Civil Action No. 11-5304, 08-08
OPINION
PISANO, District Judge
Plaintiffs Bernadette Glynn and Richard Glynn (“Plaintiffs”) bring this lawsuit against
Defendant Merck, Sharp, & Dohme Corp. (“Defendant”), which manufactures Fosamax, a drug
approved by the United States Food and Drug Administration (“FDA”) for the treatment and
prevention of osteoporosis.
This matter is part of the multi-district litigation concerning
Fosamax and involves allegations that Fosamax causes atypical femur fractures (“AFFs1”) and
that it caused Plaintiff Mrs. Glynn (“Mrs. Glynn”)’s femur fracture. Presently before the Court is
Defendant’s Omnibus Daubert Motion to exclude the expert testimony of Dr. Charles N. Cornell
(“Dr. Cornell”), Dr. Michael J. Klein (“Dr. Klein”), Dr. David Madigan (“Dr. Madigan”), and
Dr. Cheryl Blume (“Dr. Blume”) as well as a motion to exclude the causation testimony of the
treating physicians — Dr. Robert Busch (“Dr. Busch”), Dr. Robert Lindsay (“Dr. Lindsay”), Dr.
1
The abbreviation of atypical femur fracture (singular) is “AFF.”
1
Frederick Fletcher (“Dr. Fletcher”), and Dr. Britton Limes (“Dr. Limes”) [docket # 28]. This
Court heard oral argument on February 21, 2013 and April 2, 2013. For the reasons outlined
below, the Motion is denied as to Drs. Cornell, Klein, Madigan, and Blume. The treating
physicians’ causation testimony will not be excluded if their opinions are based on their
treatment and care of Mrs. Glynn.
I.
DISCUSSION
Federal Rule of Evidence 702 provides that a witness
qualified as an expert by knowledge, skill, experience, training, or
education may testify in the form of an opinion or otherwise if:
(a) the expert’s scientific, technical, or other specialized
knowledge will help the trier of fact to understand the evidence or
to determine a fact in issue;
(b) the testimony is based on sufficient facts or data;
(c) the testimony is the product of reliable principles and methods;
and
(d) the expert has reliably applied the principles and methods to the
facts of the case.
This Rule requires the proponent of expert testimony to show the “requisite ‘qualifications,
reliability, and fit’” or in other words, that “(1) the witness is qualified as an expert in a particular
field; (2) the methodology applied by the witness is sufficiently reliable; and (3) the witness’s
testimony ‘fits’ the facts of the case in dispute – that is, the proffered testimony would assist the
trier of fact.” Jones v. Synthes USA Sales, LLC, 2010 WL 3311840, *4 (D.N.J. Aug. 19, 2010);
see also McNamara v. Kmart Corp., 380 Fed. Appx. 148, 151 (3d Cir. 2010); Meadows v.
Anchor Longwall & Rebuild, Inc., 306 Fed. Appx. 781, 788 (3d Cir. 2009); Pineda v. Ford
Motor Co., 520 F.3d 237, 244 (3d Cir. 2008); Schneider ex rel. Estate of Schneider v. Fried, 320
F.3d 396, 404 (3d Cir. 2003).
2
First, the expert must be qualified; this requirement is interpreted liberally and “a broad
range of knowledge, skills, and training qualify an expert as such.” In re Paoli R.R. Yard PCB
Litigation, 35 F.3d 717, 741 (3d Cir. 1994).
Second, “an expert’s testimony is admissible so long as the process or technique the
expert used in formulating the opinion is reliable.” Id. at 742. An expert’s opinion is reliable if
it is “based on ‘good grounds,’ i.e., if it is based on the methods and procedures of science.” Id.
at 744. This inquiry requires a court to examine the “scientific validity and thus the evidentiary
relevance and reliability [] of the principles that underlie a proposed submission” and to focus
“solely on principles and methodology, not on the conclusions . . . [the expert] generate[s].”
Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 594-95 (1993). In Daubert, the
Supreme Court outlined several factors that a court may take into consideration in determining
reliability, including whether the hypothesis can be tested, whether the methodology “has been
subjected to peer review and publication,” the methodology’s rate of error, “the existence and
maintenance of standards controlling the technique’s operation,” and whether there is general
acceptance in the scientific community. Id. at 593-94. The proponent of the expert testimony
must demonstrate that the opinions are reliable by a preponderance of the evidence. In re Paoli,
35 F.3d at 744.
Third, expert testimony “must fit the issues in the case” or in other words, “be relevant
for the purposes of the case and must assist the trier of fact.” Schneider, 320 F.3d at 404. The
Court must determine “whether [the] expert testimony proffered . . . is sufficiently tied to the
facts of the case that it will aid the jury in resolving a factual dispute.” United States v. Schiff,
602 F.3d 152, 173 (3d Cir. 2010). This standard “is not that high” but “higher than bare
relevance.” In re Paoli, 35 F.3d at 745.
3
The Court’s role, at a Daubert hearing, is to act “as a gatekeeper, preventing opinion
testimony that does not meet the requirements of qualification, reliability and fit from reaching
the jury.” Schneider, 320 F.3d at 404. In keeping with its gatekeeping role, this Court will apply
the Daubert analysis to each expert.
A.
Dr. Cornell
Plaintiffs offer Dr. Cornell, an orthopedist, as an expert in causation, to establish that
Fosamax causes AFFs and Mrs. Glynn’s Fosamax use caused her AFF.
1.
Dr. Cornell Is Qualified as an Expert
Dr. Cornell is currently a Professor of Clinical Orthopedic Surgery at Weill Cornell
College of Medicine and has been the Richard Laskin Chair in Orthopedic Surgery since 2011
[docket # 102, Ex. 8, Dr. Cornell’s Report (“Cornell Report”) at 2]. In addition, Dr. Cornell is an
attending orthopedic surgeon at the Hospital for Special Surgery in New York City and currently
serves as the hospital’s Director of the Department of Orthopedic Surgery.
Id.
He is a
“specialist in orthopedic trauma . . . and metabolic bone disease,” which includes osteoporosis
and osteopenia [docket # 102, Ex. 10, Dr. Cornell’s Deposition (“Cornell Dep.”) at 69:13-16;
71:14-17]. About 80% of all the fractures Dr. Cornell treats surgically are fractures “as a
consequence of osteoporosis or osteopenia.” Id. at 72:6-21. He has treated two patients with
atypical fractures related to bisphosphonate use. Cornell Report at 3.
Moreover, he has
“participated in a study to determine a management strategy for the treatment of symptomatic
bisphosphonate-associated incomplete atypical femoral fractures, which was peer reviewed and
published in the Hospital for Special Surgery Journal.” Id. Although Defendant argues that Dr.
Cornell is not qualified because he is not trained in epidemiology and is unfamiliar with “the
4
most basic epidemiological terms and concepts” (Db132), Dr. Cornell does not have to possess a
particular subspecialty — epidemiology — to testify as an expert. See Schneider, 320 F.3d at
406-07 (determining that testimony was improperly excluded because an individual “was not an
expert in the sub-specialty about which he opined”); Holbrook v. Lykes Bros. S. S. Co., Inc., 80
F.3d 777, 783 (3d Cir. 1996) (declaring that the lower court erred by requiring the expert to have
a particular specialization and “exact background”); see also Keller v. Feasterville Family
Health Care Ctr., 557 F. Supp. 2d 671, 675 (E.D. Pa. 2008) (recognizing that expert testimony
cannot be excluded because “the expert is without the appropriate specialization” and that “[a]
certain degree of background is not required”).
Because Dr. Cornell has the academic
background and professional experience with osteoporosis, osteopenia, and fractures associated
with those diseases, he is qualified to testify as an expert in this case. See Schneider, 320 F. 3d at
407.
2.
Dr. Cornell’s Methodology Is Sufficiently Reliable
Dr. Cornell formed his opinion using the Bradford Hill criteria, which are “nine factors
widely used in the scientific community to assess general causation.” Gannon v. United Sates,
292 Fed. Appx. 170, 173 (3d Cir. 2008); Cornell Dep. at 329:5-8. General causation is when “an
observed association between a chemical and a disease is causal.” Magistrini v. One Hour
Martinizing Dry Cleaning, 180 F. Supp. 2d 584, 592 (D.N.J. 2002), aff’d, 68 Fed. Appx. 356 (3d
Cir. 2003). The nine Bradford Hill factors are: “1. Temporal Relationship, 2. Strength of the
association, 3. Dose-response relationship, 4. Replication of the findings, 5. Biological
plausibility (coherence with existing knowledge), 6. Consideration of alternative explanations,
7. Cessation of exposure, 8. Specificity of the association, and 9. Consistency with other
knowledge.” FEDERAL JUDICIAL CENTER, REFERENCE MANUAL
2
Db13 means page 13 of Defendant’s brief.
5
ON
SCIENTIFIC EVIDENCE, at
599-600
(3d
ed.
2011),
available
http://www.fjc.gov/public/pdf.nsf/lookup/SciMan3D01.pdf/$file/SciMan3D01.pdf;
at
see
also
Gannon, 292 Fed. Appx. at 173 n.1; In re Avandia Mktg., Sales Practices & Products Liab.
Litig., 2011 WL 13576, *3 (E.D. Pa. Jan. 4, 2011); Magistrini, 180 F. Supp. 2d at 592–93.
“[O]ne or more of the factors may be absent even where a causal relationship exists and . . . no
factor is a sine qua non of causation. Magistrini, 180 F. Supp. 2d at 593 n. 9.
Dr. Cornell used the Bradford Hill criteria to form an opinion on whether Fosamax
causes AFFs. Cornell Dep. at 331:4-8; Cornell Report at 4. In applying the nine Bradford Hill
factors, he reviewed Plaintiff’s medical records from 1996 to present, the office notes and
depositions of her treating physicians, and “past and current medical literature on the topics of
osteopenia, osteoporosis and their prevention and treatment with bisphosphonate drugs including
alendronate,” particularly publications concerning the FIT and FLEX studies and that described
the appearance of AFFs. Cornell Report at 3, 4–5. He “review[ed] the original trials, the
randomized trials, that led to the approval of Fosamax for the treatment of osteoporosis, and then
wanted to review many of the case reports, the case series, the summed analysis, and some of the
review papers that took all of this information and put it into a more readily digestible form.”
Cornell Dep. at 56:13-23. Dr. Cornell attempted to “present a balanced analysis” and pointed out
studies on both sides of the issue. Id. at 58:5-16. He concluded that Fosamax can cause AFFs
and “Fosamax use was a substantial contributing factor to Mrs. Glynn’s femur fracture.” Cornell
Report at 4. The methodology Dr. Cornell used is sufficiently reliable because the Bradford Hill
criteria are “broadly accepted” in the scientific community “for evaluating causation,” Gannon,
292 Fed. Appx. at 173 n. 1, and “are so well established in epidemiological research,” In re
Avandia Mktg., Sales Practices & Products Liab. Litig., 2011 WL 13576, at *3.
6
Defendant, however, argues that Plaintiffs do not explain the scientific methodology used
by Dr. Cornell or show that his methodology is sufficiently reliable. Instead, Defendant asserts
that Dr. Cornell’s “weight-of-the-evidence” methodology just lists some studies, only some of
which support causation, and concludes that the weight of the evidence shows that Fosamax
causes AFFs. Defendant explains that this method is inadequate because Dr. Cornell does not
discuss how these studies establish causation or why certain studies outweigh others that do not
find causation. Additionally, Defendant points out that Dr. Cornell has not done an evaluation of
possible biases or confounding factors found in the studies. Because Dr. Cornell does not show
that his methodology is sufficiently reliable to show general causation, Defendant argues that he
cannot establish specific causation — that Mrs. Glynn’s Fosamax use caused her AFF.
Defendant explains that the Bradford Hill criteria do not apply to specific causation, and Dr.
Cornell’s differential diagnosis was unreliable because he did not rule out the possibility that
other things could have caused Mrs. Glynn’s fracture.
Defendant is free to address these issues on cross-examination, but Defendant’s concerns
do not prohibit Dr. Cornell from testifying as an expert because he is qualified and the
methodology he used is sufficiently reliable. See Milward v. Acuity Specialty Products Group,
Inc., 639 F.3d 11, 15 (1st Cir. 2011), cert. denied, 132 S. Ct. 1002 (2012) (stating “Daubert does
not require that a party who proffers expert testimony carry the burden of proving to the judge
that the expert’s assessment of the situation is correct”; instead, the “proponent of the evidence
must show only that ‘the expert’s conclusion has been arrived at in a scientifically sound and
methodologically reliable fashion.’”).
Regarding Dr. Cornell’s specific causation opinion that Fosamax caused Mrs. Glynn’s
femur fracture, he applied the differential diagnosis method, which is “a technique that involves
7
assessing causation with respect to a particular individual.” Kannankeril v. Terminix Int’l, Inc.,
128 F.3d 802, 807 (3d Cir. 1997). It “is a process by which a physician rules out alternative
causes through review of a patient’s medical histories and records, physical examination of the
patient, laboratory testing, study of relevant medical literature, and other techniques.” In re Diet
Drugs (Phentermine/Fenfluramine/Dexfenfluramine) Products Liab. Litig., 890 F. Supp. 2d 552,
561 (E.D. Pa. 2012). The “technique is generally accepted in the medical community.” Id.
Here, Dr. Cornell applied the differential diagnosis method by examining Mrs. Glynn’s
past medical history and conducting his own examination of her on September 26, 2012, after
which he concluded that “[t]o a reasonable degree of medical certainty, Mrs. Glynn suffered a
nontraumatic [AFF] in the setting of seven years of full dose Fosamax and alendronate therapy.”
Cornell Report at 34-36. Dr. Cornell reviewed radiographs taken on April 17, 2009 to evaluate
the fracture and reviewed follow-up X-rays, hospital records, rehabilitation records, orthopedics
records, prescription records from pharmacies, and deposition transcripts, among other things, in
forming his opinion [docket # 109, Ex. 78, Appendix B to Cornell Report]. He ruled out
possible alternative causes of Mrs. Glynn’s AFF. Cornell Report at 38–40, 42–43, 45–46. Dr.
Cornell did not have to “rule out every possible alternative cause of” Mrs. Glynn’s AFF; instead,
only “[o]bvious alternative causes need to be ruled out.” Heller v. Shaw Indus., Inc., 167 F.3d
146, 156 (3d Cir. 1999). Thus, Dr. Cornell applied the differential diagnosis method in arriving
at his conclusion that Mrs. Glynn’s Fosamax use was a substantial contributing factor to her
AFF.
Therefore, the methodology used by Dr. Cornell in arriving at both his general and
specific causation opinions is sufficiently reliable.
8
Both the Bradford Hill criteria and
differential diagnosis are widely used and accepted in the scientific community to arrive at
causation opinions.
3.
Dr. Cornell’s Testimony Fits the Facts of the Case
Finally, Dr. Cornell’s testimony fits the facts of the dispute and will assist the trier of fact
because Plaintiffs seek to show that Mrs. Glynn’s AFF was caused by her Fosamax use and Dr.
Cornell not only opines that AFFs are caused by long term bisphosphonate use, like Fosamax,
but also that Mrs. Glynn’s Fosamax use was a “substantial contributing factor to her” AFF. See
Cornell Report at p. 22, 47. Consequently, Dr. Cornell’s proffered testimony will assist the trier
of fact in determining whether Fosamax caused Mrs. Glynn’s AFF.
Because Dr. Cornell is qualified, used a methodology that is sufficiently reliable, and his
opinion fits the facts of a case, his expert testimony is admissible under Daubert.
B.
Dr. Klein
Plaintiffs asked Dr. Klein, a pathologist, to offer his opinion on whether Fosamax use
causes AFFs and the “mechanism by which those fractures are precipitated” [docket #103, Ex.
11, Dr. Klein’s Report (“Klein Report”) at 2].
1.
Dr. Klein Is Qualified as an Expert
Dr. Klein is currently the Director of Pathology and Laboratory Medicine at the Hospital
for Special Surgery where he has “direct clinical responsibilities for patients . . . .” Id. at 3-4. He
also has “direct clinical responsibilities . . . as a consultant at Memorial Sloan-Kettering Cancer
Center, and as an outside counsel for leading pathology laboratories at major hospitals and
institutions around the country.” Id. at 4. Dr. Klein has reviewed the pathology for at least four
patients with AFFs [docket # 105, Ex. 37, Dr. Klein’s Deposition (“Klein Dep.”) at 41:4-12].
Dr. Klein is currently a Professor of Pathology and Laboratory Medicine at Weill Cornell
9
Medical College. Klein Report at 3. He is involved with several publications, including as the
lead author and editor of Non-neoplastic Diseases of Bones and Joints, the only peer-reviewed,
comprehensive textbook on the issue, and as a member of the editorial boards of Human
Pathology, Skeletal Radiology, Advances in Anatomical Pathology, and HSS Journal. Id. Dr.
Klein is the Consultant Editor of Research for The Journal of Bone and Joint Surgery
(American) and has authored or co-authored more than 180 articles, most of which relate to bone
pathology. Id. Therefore, Dr. Klein possesses “a broad range of knowledge, skills, and training”
to qualify him as an expert in pathology. In re Paoli, 35 F.3d at 741.
2.
Dr. Klein’s Methodology Is Sufficiently Reliable
Like Dr. Cornell, Dr. Klein used the Bradford Hill criteria to form his opinion. Klein
Report at 2. As discussed above, the Bradford Hill methodology is sufficiently reliable because
it is “widely used in the scientific community to assess general causation.” Gannon, 292 Fed.
Appx. at 173. In applying the nine Bradford Hill criteria, Dr. Klein reviewed human and animal
studies and studies performed by Defendant to form his opinion. See Klein Report at19-38. The
studies revealed a strong association between bisphosphonates, like Fosamax, and microdamage
in the bones as well as decreased bone toughness. See id. at 20, 25-30, 32. In addition, Dr. Klein
noted a strong association between delayed fracture healing, due to altered bone quality, in
patients and animals taking bisphosphonates. Id. at 23-24, 29. These findings were replicated in
several studies discussed in Dr. Klein’s report. Moreover, Dr. Klein cited one study which
recognized the “duration-dependent, as well as dose-dependent, effect bisphosphonates have on
the skeleton.” Id. at 27. Another study mentioned in Dr. Klein’s report noted that the “cessation
of bisphosphonate treatment may be prudent for women on therapy who sustain a nonvertebral
10
fracture.” Id. at 30. Thus, Dr. Klein applied the Bradford Hill criteria, including the strength of
association, replication of findings, dose-response relationship, and cessation of exposure factors.
Based on his review of the studies, Dr. Klein concluded that “alendronate significantly
alters the cellular properties of bisphosphonate-treated bone.” Id. at 38. AFFs are not
attributed to low bone mass or osteoporosis alone, indicative of
bone that has fundamentally compromised bone microstructure.
Unless a damaging force exerts tension across the entire cortex, the
laws of physics and biomechanics as applied to bone further
support the conclusion that bone quality and microstructure must
be fundamentally compromised for a transverse fracture in a
hollow cylinder[, like the femur,] to follow.
[Id.]
Thus, Dr. Klein opined that there is a causal relationship between Fosamax and AFFs. Id. at 2.
He used a sufficiently reliable methodology, the Bradford Hill criteria, in forming this opinion.
Defendant, however, argues that the Bradford Hill criteria apply to epidemiology studies,
which Dr. Klein’s report does not discuss. Defendant contends that Dr. Klein has not provided
support for the proposition that a general causation conclusion can be established using the
Bradford Hill criteria and human or animal biopsy data. In addition, Defendant asserts that if Dr.
Klein discussed epidemiology studies in his report, he did not demonstrate that he is qualified to
interpret that evidence because he has no expertise in epidemiology and does not understand the
most basic epidemiology terms. Moreover, Defendant points out that Dr. Klein conceded that
the mechanism regarding how bisphosphonates cause AFFs has not been established and that the
theories Dr. Klein uses to support his conclusion about mechanism — microdamage, decrease in
tissue heterogeneity, bone brittleness, and delayed healing — have not been proved with human
data.
11
Yet, Dr. Klein has properly applied the Bradford Hill criteria to epidemiological studies.
Epidemiological studies include randomized trials in which one group is exposed to an agent,
such as Fosamax, and another group is not, and the effect of the agent or lack thereof is
observed. FEDERAL JUDICIAL CENTER, REFERENCE MANUAL ON SCIENTIFIC EVIDENCE at 555-56.
Here, Dr. Klein examined randomized trials, such as Dempster et al., Boskey et al., and Donnelly
et al.; in each of these studies, some women were given alendronate or another bisphosphonate
and others were not. Klein Report at 20-21. Moreover, the Federal Judicial Center’s Reference
Manual on Scientific Evidence states that “toxicology models based on live animal studies . . .
may be used to determine toxicity in humans” in addition to observational epidemiology.
FEDERAL JUDICIAL CENTER, REFERENCE MANUAL ON SCIENTIFIC EVIDENCE, at 563.
For his testimony to be admissible, Dr. Klein is not required to show that the mechanism
has been definitely established. Instead, he just needs to show that the methodology he used to
arrive at his opinion is sufficiently reliable. See Milward, 639 F.3d at 15 (stating “Daubert does
not require that a party who proffers expert testimony carry the burden of proving to the judge
that the expert’s assessment of the situation is correct”; instead, the “proponent of the evidence
must show only that ‘the expert’s conclusion has been arrived at in a scientifically sound and
methodologically reliable fashion.’”). Dr. Klein arrived at his opinion on the mechanism by
examining several studies and using a scientific method that is sufficiently reliable.
3.
Dr. Klein’s Testimony Fits the Facts of the Case
Lastly, Dr. Klein’s testimony fits the facts of the dispute and will assist the trier of fact.
See Jones, 2010 WL 3311840, at *4. Through Dr. Klein’s testimony, Plaintiffs seek to show that
Fosamax causes AFFs and the mechanism by which this happens. See Klein Report at 2. Dr.
Klein opines that Fosamax causes AFFs and discusses several ways this happens —
12
microdamage, abnormal osteoclasts, altered bone quality, and delayed fracture healing. Thus,
Dr. Klein’s testimony will assist the trier of fact in determining whether Fosamax causes AFFs,
the ways in which this happens, and ultimately, his testimony will aid the jury in deciding
whether Mrs. Glynn’s Fosamax use caused her AFF.
C.
Dr. Madigan
Plaintiffs asked Dr. Madigan, a statistician, to give his opinion regarding “whether a
signal of problematic oversuppression of bone turnover and associated [AFF] . . . existed for
Fosamax, using industry standard pharmacovigilance techniques and data sources, and the
adverse event terms selected by Merck to internally evaluate the same” and “assess the strength
of that signal, if any, in comparison to the signal, if any, for such events in other products
indicated for the prevention and treatment of osteoporosis” [docket # 33, Ex. 30, Dr. Madigan’s
Report (“Madigan Report”) at ¶ 5].
1.
Dr. Madigan Is Qualified as an Expert
Dr. Madigan is Professor and Chair of Statistics at Columbia University. Id. at ¶ 1. He is
an elected Fellow of the Institute of Mathematical Statistics and the American Statistical
Association, and from 1995 to 2005 was the 36th most cited mathematician worldwide. Id. In
2010, he completed a term as Editor of the journal Statistical Science. Id. Dr. Madigan has
consulted for companies such as Novartis, Pfizer, and Sanofi-Aventis on several issues, “many
related to drug safety.” Id. at ¶ 2. He has statistical experience with clinical trials and has
published more than 100 technical papers on many topics, including pharmacovigilance3. Id.
Within the last few years, drug safety “with a focus on the development and application
of statistical methods for pharmacovigilance” has been “one of [Dr. Madigan’s] significant
3
Pharmacovigilance is the surveillance of spontaneous reporting system (“SRS”) databases “for the early detection
of drug hazards that are novel by virtue of their clinical nature, severity, and/or frequency.” Id. at ¶ 7.
13
research interests . . . .” Id. at ¶ 3. He has published work in several journals, including Drug
Safety, Pharmacoepidemiology and Drug Safety, and Epidemiology. Id. Dr. Madigan is an
investigator in the Mini-Sentinel project, which is “a pilot project sponsored by the FDA to
inform and facilitate development of a fully operational active surveillance system, the Sentinel
System, for monitoring the safety of FDA-regulated medical products.” Id. He is the “methods
lead for the Observational Medical Outcomes Partnership, a public-private partnership between
the FDA and the pharmaceutical industry, which addresses “research methods that are feasible
and useful to analyze existing healthcare databases to identify and evaluate safety and benefit
issues of drugs already on the market.” Id. Dr. Madigan is a member of the FDA’s Drug Safety
and Risk Management Committee, which “advises the FDA Commissioner on risk management,
risk communication, and quantitative evaluation of spontaneous reports for drugs for human use
and for any other product for which the FDA has regulatory responsibility.” Id. Dr. Madigan is
qualified as an expert because he has “a broad range of knowledge, skills, and training [to]
qualify . . . [him] as such.” In re Paoli, 35 F.3d at 741. Defendant does not dispute Dr.
Madigan’s qualifications.
2.
Dr. Madigan’s Methodology Is Sufficiently Reliable
Dr. Madigan examined the FDA’s Adverse Event Reporting System (“AERS”) database
for a “possible association between Fosamax and a series of . . . terms selected by Merck to
evaluate oversuppression of bone turnover and associated” AFFs. Madigan Report at ¶ 25. The
terms were: bone development abnormal, bone disorder, bone formation decreased, fracture
delayed union, fracture malunion, fracture nonunion, low turnover osteopathy, pathological
fracture, stress fracture, fracture, and femur fracture. Id. at ¶ 26. Dr. Madigan used “two
industry-standard signal detection algorithms . . . to assess whether or not Fosamax presented a
14
safety signal” indicating oversuppression of bone turnover or AFFs. Id. at ¶ 25. The QScan
pharmacovigilance software computed the statistics. Id. at ¶ 27. Dr. Madigan then compared the
Fosamax signals to other oral bisphosphonates and a non-bisphosphonate used for the treatment
and prevention of osteoporosis. Id. at ¶ 25. After reviewing the data, Dr. Madigan opined that
industry standard pharmacovigilance techniques and datasources
reveal the presence of a clear signal for oversuppression of bone
turnover and associated atypical femur fracture events utilizing the
terms selected by Merck for such analysis. By standard metrics of
“signal” detection, the signal is strong, consistent, and not
ambiguous. Of perhaps greater concern, the signal was striking in
comparison to that for other drugs indicated for the prevention and
treatment of osteoporosis. As early as 2001-2002, the spontaneous
report data for Fosamax provide signals for a number of indicators
of suppression of bone turnover. For the comparator drugs, such
signals either never appear or appear years later.
[Id. at ¶ 36.]
This opinion is admissible because it is based on a method that is sufficiently reliable.
See Jones, 2010 WL 3311840, at *4. Two factors that a court may take into consideration in
determining reliability is whether the methodology has been subjected to peer review and
publication and whether there is general acceptance in the scientific community. Daubert, 509
U.S. at 593-94. Here, Dr. Madigan’s method, data mining in pharmacovigilance, is generally
accepted in the scientific community and has “become routine both in the pharmaceutical
industry and amongst regulators worldwide.” Madigan Report at ¶ 8. In fact, “[p]harmaceutical
companies, health authorities, and drug monitoring centers use SRS databases for global
screening for signals of new adverse events or changes in the frequency, character, or severity of
existing adverse events (AEs) after regulatory authorization for use in clinical practice.” Id. at ¶
9. “SRS systems provide the primary data for day-to-day drug safety surveillance by regulators
and manufacturers worldwide.” Id. at ¶ 14. In addition, the QScan software Dr. Madigan used
15
in formulating his opinion is generally accepted by the scientific community because it “has been
in widespread use for over 10 years and has been validated extensively.” Id. at ¶ 28. Moreover,
“[m]any peer-reviewed publications report results derived from QScan.”
Id.
Thus, Dr.
Madigan’s methodology is sufficiently reliable.
Although Defendant argues that Dr. Madigan’s methodology is unreliable because he did
not review the substance of the adverse event reports to see if they actually involve AFFs or
oversuppression of bone turnover, this argument is inappropriate on a Daubert motion. Dr.
Madigan’s testimony will be subject to cross-examination, and the credibility of his opinion will
be ultimately determined through the adversarial process.
Dr. Madigan’s methodology is
sufficiently reliable because it is generally accepted in the scientific community, and therefore,
Plaintiffs have satisfied the second prong of Daubert.
3.
Dr. Madigan’s Testimony Fits the Facts of the Case
Lastly, Dr. Madigan’s testimony fits the facts of the case and will assist the trier of fact
because it is related to Plaintiffs’ failure to warn claim. See Jones, 2010 WL 3311840, at *4. A
failure to warn claim requires a plaintiff to show “(1) that a manufacturer has a duty to warn (2)
against dangers resulting from foreseeable uses about which it knew or should have known and
(3) that failure to do so was the proximate cause of the harm.” In re Fosamax Prods. Liab. Litig.,
2013 WL 76140, *3 (S.D.N.Y. Jan. 7, 2013). Dr. Madigan’s testimony fits the facts of this case
because he opines that “[a]s early as 2001-2002, the spontaneous report data for Fosamax
provide[d] signals for a number of indicators of suppression of bone turnover,” meaning
Defendant knew or should have known that Fosamax caused certain dangers in 2001-2002, thus
imposing on Defendant a duty to warn of those dangers. Madigan Report at ¶ 36.
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Defendant, however, argues that Dr. Madigan’s testimony does not fit the facts of the
case because it is irrelevant since there is no reasonable standard of care that would have
required Defendant to conduct data mining. This is also a matter best left to the credibility
determination of the jury.
As a result, Dr. Madigan’s expert testimony is admissible under Daubert because he is
qualified, he used a sufficiently reliable methodology, and his opinion fits the facts of the case.
D.
Dr. Blume
Dr. Blume is offered as an expert in pharmacovigilance and FDA regulation. Plaintiffs
offer the testimony of Dr. Blume to: (1) “address the timeliness and completeness of the efforts
undertaken by [Defendant] . . . to fully inform prescribers and patients of the increasingly
adverse benefit risk assessments associated with long-term Fosamax use in postmenopausal
women”; (2) “evaluate the negative consequences of protracted bone oversuppression,”
including AFFs, in people receiving Fosamax; and (3) “to consider the pharmacovigilance
activities undertaken by [Defendant] to evaluate the noted adverse events during the relevant
time periods” [docket # 119, Ex. 33, Dr. Blume’s Report (“Blume Report”) at ¶ 6].
1.
Dr. Blume is Qualified as an Expert
Dr. Blume received her Ph.D. in Pharmacology and Toxicology from the West Virginia
University Medical Center and is currently the President of Pharmaceutical Development Group,
Inc. (PDG), “a consulting firm . . . specializing in pharmaceutical development and registration
activities.” Id. at ¶ 1. In this role, she “has been responsible for preclinical and clinical (Phases
I-IV) programs associated with pharmaceutical product development and the securing of premarketing approvals” for many drugs before the FDA. Id. at ¶ 2. Additionally, Dr. Blume has
directed “all phases of interactions with [the] FDA relating to the prosecution of New Drug
17
Applications (NDAs), Abbreviated New Drug Applications (ANDAs), Supplements to New
Drug Applications (sNDAs), and the associated approval procedures,” including “the collection
and evaluation of postmarketing adverse medical events, the preparation of updated product
labeling, and the dissemination of accurate, complete and timely product-related information to
health care providers.” Id. at ¶ 3. She was responsible for “regulatory review of promotional
and education materials for both brand-name and generic drug products.” Id. Dr. Blume’s
responsibilities include the “design, execution, and interpretation of pivotal safety-related trials
and the development and implementation of pharmacovigilance procedures intended to detect
new safety signals and track the evolution of previously identified signals.” Id. at ¶ 4. She has
directed “all phases of interactions with the FDA relating to post-approval labeling procedures
regarding changes to safety-related information based upon postmarketing signal tracking and
pharmacovigilance efforts,” including “collection and evaluation of postmarketing adverse
medical events, review and interpretation of the results of postmarketing clinical studies, the
preparation of updated product labeling and other communication tools, and the dissemination of
new product information to health care providers, patients, and consumers.” Id. at ¶ 5. Dr.
Blume possesses the knowledge, skills, and training necessary to qualify her as an expert. See In
re Paoli, 35 F.3d at 741. Defendant does not dispute Dr. Blume’s qualifications.
2.
Dr. Blume’s Methodology Is Sufficiently Reliable
Dr. Blume reviewed published studies (Blume Report at ¶¶ 57-74), Merck’s Period
Safety Update Reports (id. at ¶ 75), Dr. Madigan’s report (id. at ¶¶ 76-78), Merck’s Worldwide
Adverse Experience System (“WAES”) (id. at ¶ 79), and epidemiological studies (id. at ¶¶ 8290). See also docket # 119, Ex. 5, Dr. Blume’s Deposition (“Blume Dep.”) at 148:9-18; 338:920 (stating that she looked at the WAES database, literature reports, epidemiological studies, the
18
AERS database, and Dr. Madigan’s report). She discussed the “specific regulatory procedures
and regulations” pharmaceutical manufacturers have to comply with, including procedures and
regulations related to FDA approval, labeling, postmarketing surveillance, and reporting
requirements. Id. at ¶¶ 11-34. Dr. Blume evaluated all of this information using “her years of
experience” in “the industry,” see In re Viagra Products Liability Litigation, 658 F. Supp. 2d
950, 962 (D. Minn. 2009), and opined that
the scientific literature, Merck’s internal adverse event database,
the AERS database, and epidemiology analyses confirmed the
increasingly adverse risk-benefit profile related to long-term
Fosamax use in the indicated populations. However, Merck
permitted their labeling and other prescriber information to remain
static with respect to both the deteriorating risk-benefit assessment
and the escalation in . . . [AFF] reports. Such omissions do not
comply with the regulatory and industry standards of responsible
pharmaceutical companies . . . . Merck also should have
undertaken timely and adequate studies to more clearly elucidate
the risks of Fosamax use in the various indicated populations.
Finally, Merck should have disseminated Dear Healthcare
Professional Letters to advise prescribers and their patients of the
escalating safety and efficacy concerns. Merck’s omissions have
likely resulted in the exposure of numerous patient populations to
unnecessary risks associated with the initiation and ongoing
treatment with Fosamax.
[Blume Report at ¶ 110.]
Dr. Blume states that “[b]y the early 2000’s, it was known that . . . [AFFs] were clinically
significant events . . . .” Id. at ¶ 109. Dr. Blume opines that Defendant should have changed the
Fosamax label “to include escalating warning and precautionary risk information related to”
AFFs. Id. Instead, Dr. Blume notes that Defendant “did not identify these fractures in the
labeling until 2009” even though it received reports that AFFs were “associated with Fosamax
use as early as 2002.” Id. at ¶¶ 31, 82.
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Defendant argues that the Court should exclude Dr. Blume’s opinions on: (1) the legal
requirements governing pharmaceutical manufacturers and Defendant’s compliance with those
requirements; (2) Defendant waiting too long to add information about femur fractures to the
Adverse Reactions section of the label; (3) Defendant failing to add a warning or precaution
about femur fractures to the Fosamax label before 2009; (4) Defendant’s failure to timely
investigate a potential link between Fosamax and AFF; (5) Defendant’s alleged motives or state
of mind; (6) the causation or mechanism of AFF; and (7) the drug Evista is safer than Fosamax.
Yet, because Daubert concerns the narrow issue of whether expert testimony is admissible, this
is not the appropriate time for Defendant to request that the Court preclude Dr. Blume from
testifying about certain topics. Defendant may question Dr. Blume’s opinions or methodology
on cross-examination. See Milward, 639 F.3d at 15 (stating “[s]o long as an expert’s scientific
testimony rests upon “good grounds,” based on what is known, . . . , it should be tested by the
adversarial process, rather than excluded”).
Despite Defendant’s issues with Dr. Blume’s opinions, Plaintiffs have satisfied the
second prong of Daubert because Dr. Blume’s methodology is sufficiently reliable.
3.
Dr. Blume’s Testimony Fits the Facts of the Case
Dr. Blume’s testimony fits the facts of the case because she opines that it was known in
the early 2000’s that AFFs were associated with Fosamax use. See Blume Report at ¶¶ 31, 82.
Dr. Blume’s testimony is relevant and will assist the trier of fact in deciding Plaintiffs’ failure to
warn claim because Dr. Blume’s opinion is relevant to whether and when Defendant knew or
should have known that AFFs were associated with Fosamax and therefore, when Defendant
should have sought a label change. See Schneider, 320 F.3d at 404 (recognizing that expert
testimony must “be relevant for the purposes of the case and must assist the trier of fact”).
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E.
Treating Physicians
Defendant argues that the Court should preclude causation testimony from Plaintiffs’
treating physicians — Drs. Busch, Lindsay, Fletcher, and Limes — because: (1) Plaintiffs have
not provided Rule 26 disclosures for any of the treating physicians; and (2) none of the treating
physicians are able to offer a reliable causation opinion to a reasonable degree of medical
certainty. Plaintiffs, however, assert that they do not intend to elicit expert testimony from the
treating physicians; instead, the treating physicians will testify about Mrs. Glynn’s care and
treatment, which does not require Rule 26 disclosures.
Treating “physicians are not required to submit expert reports when testifying based on
their examination, diagnosis and treatment of a patient.”
Patterson v. Howard, 2010 WL
1050052, *4 (D.N.J. Mar. 18, 2010). Federal Rule of Civil Procedure 26(a)(2)(B) requires a
witness to submit a written report only “if the witness is one retained or specially employed to
provide expert testimony in the case or one whose duties as the party’s employee regularly
involve giving expert testimony.” A “treating physician is not necessarily retained or specially
employed to provide expert testimony simply because he or she proffers on causation and
prognosis” because “doctors may need to determine the cause of an injury in order to treat it.”
Pease v. Lycoming Engines, 2012 WL 162551, *12 (M.D. Pa. Jan. 19, 2012). In order to
“determine whether a party retained or specially employed a treating physician to provide expert
testimony,” the Court must examine “whether the treating physician acquired his opinion as to
the cause of . . . plaintiff’s injuries directly through his treatment of the plaintiff.” Id. (internal
quotation omitted). As a result, treating physicians are not required to submit expert reports “if
they form their opinion on causation or prognosis as part of the ordinary care of a patient.” Id.
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Therefore, the testimony of Drs. Busch, Lindsay, Fletcher, and Limes is appropriate if it
is based on their care and treatment of Mrs. Glynn. This Court will not allow, however, any
expert testimony on causation from these physicians.
II.
CONCLUSION
For the reasons outlined above, this Court denies Defendant’s Daubert Motion as to Drs.
Cornell, Klein, Madigan, and Blume. An appropriate Order accompanies this Opinion.
Dated: April 10, 2013
/s/ Joel A. Pisano
JOEL A. PISANO
United States District Judge
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