govinfo:USCOURTS-njd-1_08-cv-00008-4

1 
 
NOT FOR PUBLICATION 
 
 UNITED STATES DISTRICT COURT 
DISTRICT OF NEW JERSEY 
 
 
 : 
IN RE: FOSAMAX (ALENDRONATE SODIUM) : 
PRODUCTS LIABILITY LITIGATION : 
 : 
_________________________________________ : 
 : 
BERNADETTE GLYNN and RICHARD GLYNN, : Civil Action No. 11-5304, 08-08 
 : 
 Plaintiffs, : OPINION 
 : 
 v . : 
 : 
MERCK SHARP & DOHME CORP, : 
 : 
 Defendant. : 
 : 
 
PISANO, District Judge 
 
 Plaintiffs Bernadette Glynn and Richard Glynn (“Plaintiffs”) bring this lawsuit against 
Defendant Merck, Sharp, & Dohme Corp. (“Defenda nt”), 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 allegati ons that Fosamax causes atypical femur fractures (“AFFs
1”) 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. Kl ein”), Dr. David Madiga n (“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. Busc h”), Dr. Robert Lindsay (“Dr. Lindsay”), Dr. 
                                                             
1 The abbreviation of atypical femur fracture (singular) is “AFF.” PageID:
<pageID>
2 
 
Frederick Fletcher (“Dr. Fletch er”), 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. Corn ell, Klein, Madigan, and Blume. The treating 
physicians’ causation testimony w ill 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, te chnical, or othe r specialized 
knowledge will help the trier of f act 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 th e “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 re liable; 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). PageID:
<pageID>
3 
 
First, the expert must be qualified; this requi rement is interpreted liberally and “a broad 
range of knowledge, skills, and traini ng 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 base d 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 th at underlie a proposed s ubmission” and to focus 
“solely on principles and methodology, not on the c onclusions . . . [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 cour t 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 methodol ogy’s rate of error, “the existence and 
maintenance of standards contro lling the technique’s operation,” and whether th ere 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 tes timony proffered . . . is sufficiently tied to the 
facts of the case that it will aid the ju ry 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. PageID:
<pageID>
4 
 
The Court’s role, at a Daubert hearing, is to act “as a ga tekeeper, 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 C linical 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. H e i s a 
“specialist in orthopedic trauma . . . and meta bolic bone disease,” whic h includes osteoporosis 
and osteopenia [docket # 102, Ex. 10, Dr. Cornel l’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 fe moral 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 trai ned in epidemiology and is unfamiliar with “the PageID:
<pageID>
5 
 
most basic epidemiological terms and concepts” (Db13 2), Dr. Cornell does not have to possess a 
particular subspecialty — epidemio logy — to testify as an expert. See Schneider , 320 F.3d at 
406-07 (determining that testimony was improperly ex cluded because an individual “was not an 
expert in the sub-specialt y about which he opined”); Holbrook v. Lykes Bros. S. S. Co., Inc. , 80 
F.3d 777, 783 (3d Cir. 1996) (declaring that the lowe r court erred by requiring the expert to have 
a particular specializati on 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 experi ence with osteoporosis, osteopeni a, 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 chem ical 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 Hi ll factors are: “1. Temporal Relationship, 2. Strength of the 
association, 3. Dose-response relationship, 4. Replication of the findings, 5. Biological 
plausibility (coherence with exis ting knowledge), 6. Consideratio n of alternative explanations, 
7. Cessation of exposure, 8. Sp ecificity of the asso ciation, and 9. Cons istency with other 
knowledge.” F EDERAL JUDICIAL CENTER, R EFERENCE MANUAL ON SCIENTIFIC EVIDENCE, at 
                                                             
2 Db13 means page 13 of Defendant’s brief. PageID:
<pageID>
6 
 
599-600 (3d ed. 2011), available at 
http://www.fjc.gov/public/pdf.nsf/lookup/SciMan3D01.pdf/$file/SciMan3D01.pdf; 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 ma y 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 Repor t 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 physicia ns, and “past and current medical literature on the topics of 
osteopenia, osteoporosis and their prevention and treatment with bisphosphonate drugs including 
alendronate,” particularly publications concerni ng 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 a nd 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 scie ntific community “for evaluating causation,” Gannon, 
292 Fed. Appx. at 173 n. 1, and “are so well es tablished in epidemio logical research,” In re 
Avandia Mktg., Sales Practices & Products Liab. Litig., 2011 WL 13576, at *3. PageID:
<pageID>
7 
 
Defendant, however, argues that Plaintiffs do not explain the scientific methodology used 
by Dr. Cornell or show that his methodology is su fficiently reliable. In stead, Defendant asserts 
that Dr. Cornell’s “weight-of-the-evidence” met hodology 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 me thod 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 th e 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 crite ria do not apply to specific causation, and Dr. 
Cornell’s differential diagnosis was unreliable becau se 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 Sp ecialty 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 pr offers expert testimony carry th e burden of proving to the judge 
that the expert’s assessment of the situation is correct”; instea d, 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 causati on opinion that Fosamax caused Mrs. Glynn’s 
femur fracture, he applied the differential diagno sis method, which is “a t echnique that involves PageID:
<pageID>
8 
 
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 proce ss by which a physician rules out alternative 
causes through review of a patient ’s medical histories and record s, physical examination of the 
patient, laboratory testing, study of relevant medical lite rature, 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 conduc ting his own examination of her on September 26, 2012, after 
which he concluded that “[t]o a reasonable degree of medical cer tainty, 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, hospita l records, rehabilitation records, orthopedics 
records, prescription records from pharmacies, a nd deposition transcripts, among other things, in 
forming his opinion [docket # 109, Ex. 78, Appe ndix 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 cause s 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 contri buting factor to her 
AFF. 
Therefore, the methodology used by Dr. Co rnell in arriving at both his general and 
specific causation opinions is sufficiently reliabl e. Both the Bradford Hill criteria and PageID:
<pageID>
9 
 
differential diagnosis are widely used and accepted in the scien tific community to arrive at 
causation opinions. 
 3. Dr. Cornell’s Testimony Fi ts 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 “s ubstantial contributing factor to her” AFF. See 
Cornell Report at p. 22, 47. Cons equently, 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 me thodology 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 precipita ted” [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 Di rector 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 leadi ng 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 Profe ssor of Pathology and Laboratory Medicine at Weill Cornell PageID:
<pageID>
10 
 
Medical College. Klein Report at 3. He is i nvolved with several publications, including as the 
lead author and editor of Non-neoplastic Diseas es 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 Bradfo rd 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 asso ciation 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 fract ure healing, due to a ltered 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 repor t. 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 fo r women on therapy who sustain a nonvertebral PageID:
<pageID>
11 
 
fracture.” Id. at 30. Thus, Dr. Klein applied the Bradfo rd 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. Klei n concluded that “alen dronate significantly 
alters the cellular properties of bisphosphonate-treated bone.” Id. at 38. AFFs are not 
attributed to low bone mass or os teoporosis alone, indicative of 
bone that has fundamentally comp romised 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 qu ality 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 cau sal 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. Defe ndant contends that Dr . Klein has not provided 
support for the proposition that a general causa tion 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 dem onstrate that he is qualified to 
interpret that evidence because he has no expe rtise 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 s upport his conclusion about mechanism — microdamage, decrease in 
tissue heterogeneity, bone brittleness, and delayed healing — have not been proved with human 
data. PageID:
<pageID>
12 
 
 Yet, Dr. Klein has properly applied the Bradford Hill criteria to epidemiological studies. 
Epidemiological studies include ra ndomized 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 we re given alendronate or another bisphosphonate 
and others were not. Klein Repor t at 20-21. Moreover, the Federa l Judicial Center’s Reference 
Manual on Scientific Evidence states that “toxico logy 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 esta blished. Instead, he ju st 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 pr offers expert testimony carry th e burden of proving to the judge 
that the expert’s assessment of the situation is correct”; instea d, 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 assi st 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 — PageID:
<pageID>
13 
 
microdamage, abnormal osteoclasts, altered bone quality, and delayed fr acture healing. Thus, 
Dr. Klein’s testimony will assist th e 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 oversuppre ssion of bone turnover and associ ated [AFF] . . . existed for 
Fosamax, using industry standard pharmacovigila nce 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 si gnal, 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 Mathema tical 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, Pfiz er, 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 pharmacovigilance
3. Id. 
Within the last few years, drug safety “with a focus on the development and application 
of statistical methods for pharmacovigilance” ha s been “one of [Dr. Madigan’s] significant 
                                                             
3 Pharmacovigilance is the surveillance of spontaneous repo rting 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. PageID:
<pageID>
14 
 
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 ope rational 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 Pa rtnership, a public-private partnership between 
the FDA and the pharmaceutical industry, which addr esses “research methods that are feasible 
and useful to analyze existing healthcare database s 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 “advise s 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 broa d 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 Ev ent 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 formati on decreased, fracture 
delayed union, fracture maluni on, fracture nonunion, low turnove r osteopathy, pathological 
fracture, stress fracture, fract ure, and femur fracture. Id. at ¶ 26. Dr. Madigan used “two 
industry-standard signal detection algorithms . . . to assess whether or not Fosamax presented a PageID:
<pageID>
15 
 
safety signal” indicating oversuppre ssion 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 pharmacovigilan ce techniques and datasources 
reveal the presence of a clear signal for oversuppression of bone 
turnover and associated atypical fe mur 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 conc ern, 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 si gnals 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 base d 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 methodol ogy 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 m onitoring 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 au thorization for use in clinical practice.” Id. at ¶ 
9. “SRS systems provide the primary data for da y-to-day drug safety surveillance by regulators 
and manufacturers worldwide.” Id. at ¶ 14. In addition, the QScan software Dr. Madigan used PageID:
<pageID>
16 
 
in formulating his opinion is generally accepted by the scientific community because it “has been 
in widespread use for over 10 years a nd has been validated extensively.” Id. at ¶ 28. Moreover, 
“[m]any peer-reviewed publications repo rt results derived from QScan.” Id. Thus, Dr. 
Madigan’s methodology is sufficiently reliable. 
 Although Defendant argues that Dr. Madiga n’s methodology is unreliable because he did 
not review the substance of the adverse event repor ts to see if they actu ally involve AFFs or 
oversuppression of bone tu rnover, this argument is inappropriate on a Daubert motion. Dr. 
Madigan’s testimony will be subject to cross-exam ination, 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 acce pted in the scientific community, and therefore, 
Plaintiffs have satisfied the second prong of Daubert. 
 3. Dr. Madigan’s Testimony Fi ts 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 us es 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 f acts 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 da ngers in 2001-2002, thus 
imposing on Defendant a duty to warn of those dangers. Madigan Report at ¶ 36. PageID:
<pageID>
17 
 
 Defendant, however, argues that Dr. Madiga n’s testimony does not f it 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 le ft to the credibility 
determination of the jury. 
As a result, Dr. Madigan’s expe rt 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 pharm acovigilance and FDA re gulation. Plaintiffs 
offer the testimony of Dr. Blume to: (1) “addres s 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 conseque nces 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 Pharmacol ogy and Toxicology from the West Virginia 
University Medical Center and is currently th e 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 res ponsible for preclinical and clinical (Phases 
I-IV) programs associated with pharmaceutical product development and the securing of pre-
marketing approvals” for many drugs before the FDA. Id. at ¶ 2. Additionally, Dr. Blume has 
directed “all phases of interactions with [t he] FDA relating to the prosecution of New Drug PageID:
<pageID>
18 
 
Applications (NDAs), Abbreviated New Drug Applications (ANDAs), Supplements to New 
Drug Applications (sNDAs), and the associated approval procedures,” in cluding “the collection 
and evaluation of postmarketing adverse medical events, the preparat ion of updated product 
labeling, and the dissemination of accurate, comple te and timely product-related information to 
health care providers.” Id. at ¶ 3. She was res ponsible for “regulatory review of promotional 
and education materials for both bra nd-name and generic drug products.” Id. Dr. Blume’s 
responsibilities include the “desi gn, execution, and interpretation of pivotal safety-related trials 
and the development and implementation of phar macovigilance procedures intended to detect 
new safety signals and track the evoluti on of previously identified signals.” Id. at ¶ 4. She has 
directed “all phases of interactions with the F DA relating to post-approva l labeling procedures 
regarding changes to safety-related informa tion based upon postmarketing signal tracking and 
pharmacovigilance efforts,” including “collecti on and evaluation of postmarketing adverse 
medical events, review and inte rpretation of the results of pos tmarketing 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 (Blu me Report at ¶¶ 57-74 ), Merck’s Period 
Safety Update Reports ( id. at ¶ 75), Dr. Madigan’s report ( id. at ¶¶ 76-78), Me rck’s Worldwide 
Adverse Experience System (“WAES”) ( id. at ¶ 79), and epidemiological studies ( id. at ¶¶ 82-
90). See also docket # 119, Ex. 5, Dr. Blume’s Depos ition (“Blume Dep.”) at 148:9-18; 338:9-
20 (stating that she looked at the WAES database , literature reports, epidemiological studies, the PageID:
<pageID>
19 
 
AERS database, and Dr. Madigan’ s report). She discussed the “s pecific regulatory procedures 
and regulations” pharmaceutical manufacturers have to comply with, including procedures and 
regulations related to FDA a pproval, labeling, postmarketi ng surveillance, and reporting 
requirements. Id. at ¶¶ 11-34. Dr. Blume eval uated all of this informa tion 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 st udies to more clearly elucidate 
the risks of Fosamax use in th e various indicated populations. 
Finally, Merck should have disseminated Dear Healthcare 
Professional Letters to advise pres cribers 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 w ith the initiati on and ongoing 
treatment with Fosamax. 
 
[Blume Report at ¶ 110.] 
 
Dr. Blume states that “[b]y th e 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 a nd 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. PageID:
<pageID>
20 
 
 Defendant argues that the Court should exclude Dr. Blume’ s opinions on: (1) the legal 
requirements governing pharmaceutical manufacture rs and Defendant’s compliance with those 
requirements; (2) Defendant wait ing too long to add information about femur fractures to the 
Adverse Reactions section of the label; (3) De fendant failing to add a warning or precaution 
about femur fractures to the Fosamax label be fore 2009; (4) Defendant’s failure to timely 
investigate a potential link betw een Fosamax and AFF; (5) Defenda nt’s alleged motives or state 
of mind; (6) the causation or mech anism of AFF; and (7) the drug Ev ista is safer than Fosamax. 
Yet, because Daubert concerns the narrow issu e of whether expert test imony is admissible, this 
is not the appropriate time fo r Defendant to request that th e Court preclude Dr. Blume from 
testifying about certai n 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. Blum e’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 rele vant 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”). PageID:
<pageID>
21 
 
 E. Treating Physicians 
 Defendant argues that th e 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 causati on opinion to a reasonable degree of medical 
certainty. Plaintiffs, however, assert that they do not intend to elicit expert testimony from the 
treating physicians; inst ead, the treating physicians will te stify about Mrs. Glynn’s care and 
treatment, which does not require Rule 26 disclosures. 
Treating “physicians are not required to subm it expert reports when testifying based on 
their examination, diagnosis a nd 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 w itness is one retained or specially employed to 
provide expert testimony in the case or one whose duties as the part y’s employee regularly 
involve giving expert testimony.” A “treating physician is not neces sarily retained or specially 
employed to provide expert testimony simply because he or she proffers on causation and 
prognosis” because “doctors may need to determine th e 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 th e treating physician acquire d his opinion as to 
the cause of . . . plaintiff’s injuries directly th rough 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. PageID:
<pageID>
22 
 
Therefore, the testimony of Drs. Busch, Linds ay, Fletcher, and Limes is appropriate if it 
is based on their care and treatment of Mrs. Gl ynn. 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 / J o e l A . P i s a n o 
 J O E L A . P I S A N O 
 United States District Judge PageID:
<pageID>

Passage view · GavelSight