Pfaff v. Merck & Co.
| Decision Date | 08 September 2022 |
| Docket Number | 15-cv-3355 (BMC),12-md-02331 (BMC) |
| Parties | KELLY S. PFAFF, et al., Plaintiffs, v. MERCK & CO., INC., et ano., Defendants. |
| Court | U.S. District Court — Eastern District of New York |
BRIAN M. COGAN U.S.D.J.
Plaintiffs bring failure-to-warn and breach of warranty claims against Merck & Co., Inc. and Merck Sharp & Dohme Corp. (together, “Merck”) for injuries arising from the death of their father and husband, John D. Pfaff. Plaintiffs argue that Pfaff's suicide was a result of Merck's failure to warn him of the hair loss drug Propecia's allegedly “dangerous side effects” including “depression and suicide ideation.”
Merck moves for partial summary judgment as to whether two of plaintiffs' arguments are preempted: that it should have (1) added a warning regarding suicidality; and (2) listed depression in the Warnings & Precautions (“W&P”) section of Propecia's label. For the reasons that follow, Merck's motion is GRANTED.
In 1997, the Federal Drug Administration (“FDA”) granted approval of Merck's drug Propecia.[1] Propecia is a one milligram tablet of finasteride, which treats androgenetic alopecia or, as it is more commonly known, male pattern hair loss. Finasteride is a selective inhibitor of Type II 5a-reductase, an enzyme that (among other things) “converts . . . testosterone into 5a-dihydrotestosterone (DHT).” Propecia was not Merck's only orally administered finasteride product. Merck also marketed Proscar, which contains five times more finasteride than Propecia.[2]
When the FDA approved Propecia for sale, it also was required to greenlight its initial label. Pursuant to the Federal Food Drug, and Cosmetic Act (“FDCA”), 21 U.S.C. § 301 et seq., the FDA strictly monitors and controls the labels for all FDA-approved drugs. When a new drug is initially approved, the FDA is responsible for approving its label, see 21 U.S.C. § 355; 21 C.F.R. § 314.105(b), and determining about which risks consumers must be warned.
Not all risks necessitate a warning on a drug label. See 21 C.F.R. § 201.57(c) (). This is because “[t]he FDA has recognized that ‘[e]xaggeration of risk, or inclusion of speculative or hypothetical risks, could discourage appropriate use of a beneficial drug . . . or decrease the usefulness and accessibility of important information by diluting or obscuring it.'” Utts v. Bristol-Myers Squibb Co., 251 F.Supp.3d 644, 659 (S.D.N.Y. 2017) (quoting Supplemental Applications Proposing Labeling Changes for Approved Drugs, Biologics, and Medical Devices, 73 Fed.Reg. 2848, 2851 (Jan. 16, 2008)). The FDA thus “seeks to allow ‘only information for which there is a scientific basis to be included.'” Id. Accordingly, the earliest version of Propecia's label did not refer to or include any warnings for depression or suicidality.
As new risks will often arise only after FDA approval, manufacturers are required to “disclose to the FDA any adverse health consequences reported” on a continuous basis. Id. at 658. This requirement includes submitting Periodic Safety Update Reports (“PSURs”) to the FDA. See 21 C.F.R § 314.80(c)(2).[3] Beginning in 1997, Merck commenced submitting such PSURs, which covered information about adverse drug reactions (“ADRs”) and new scientific and medical literature on Propecia, including those involving depression and suicidality.[4]
In early 2010, the Swedish Medical Products Agency, a Swedish regulatory agency, asked Merck to “present a cumulative review of depression, including suicide related ADRs” in future PSURs. Merck agreed. In compiling the review, Merck searched the Worldwide Adverse Events (“WAES”) database for depression and suicide related events since Propecia's approval up through April 30, 2010. After a review of the data, Merck recognized that it could not exclude a possible causal association between Propecia and “depression-related terms.”
This left Merck facing an important decision regarding how to best meet its regulatory obligations. Under FDA regulations, it was required to ensure that its warnings regarding Propecia “remain adequate as long as the drug is on the market.” Wyeth v. Levine, 555 U.S. 555, 571 (2009). However, although it bore the primary “responsibility for the content of its label at all times,” FDA regulations also forbid it from unilaterally altering Propecia's label in any respect without the express approval of the FDA. Id.
This rule against unilateral alteration is subject to one exception.[5] Drug manufacturers are permitted by the FDA to make changes to a product label prior to FDA approval in a process known as changes being effected (“CBE”). Using this process, a drug manufacturer may update its labeling of a drug to “add or strengthen a contraindication, warning, precaution, or adverse reaction for which the evidence of a causal association satisfies the standard for inclusion” where it has “newly acquired information.” 21 C.F.R § 314.70(c)(6)(iii)(A). For the purposes of the CBE process, newly acquired information includes:
[D]ata, analyses, or other information not previously submitted to the Agency, which may include (but is not limited to) data derived from new clinical studies, reports of adverse events, or new analyses of previously submitted data (e.g., meta-analyses) if the studies, events, or analyses reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA.
21 C.F.R. § 314.3(b). Where a manufacturer decides to follow the CBE process, the FDA allows it to implement labeling changes simultaneously with the submission of a supplemental application for changes to the FDA for review and approval (the “CBE supplement”). The FDA retains the authority to ultimately reject or otherwise modify the label change. See 21 C.F.R. § 314.70(c)(7).
Accordingly, on July 16, 2010, Merck decided to submit a CBE supplement to the FDA, and more specifically the Division of Dermatology and Dental Products (“DDDP”), requesting that it add “depression” to the Adverse Reaction (“AR”) section of Propecia's label. This section of a drug's label lists “undesirable effect[s]” if “there is some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.” 21 C.F.R. § 201.57(c)(7). The AR section contains less serious warnings than those found in the W&P section, which include “clinically significant adverse reactions,” where “there is reasonable evidence of a causal association.” C.F.R. § 201.57(c)(6)(i).
To assist in the review of Merck's CBE, the DDDP asked the FDA's Division of Pharmacovigilance (“DPV”) “to provide an assessment of [Merck's] request to add ‘depression' to the Propecia product label.” Rather than only relying on Merck's reports, the DVP also conducted its own research, which included analyzing all the reports of depression-related or suicide-related events associated with finasteride that were submitted to the FDA's Adverse Event Reporting System (“AERS”) up until September 25, 2020. The DVP also undertook a “[search of] the medical literature (PubMed@FDA) on September 24, 2010 for case reports of depression-related or suicide-related adverse events associated with finasteride.”[6]
Ultimately, the DVP concurred with Merck's “assessment to add depression to the Adverse Events, Postmarketing Experience section of the label.” Although Merck did not request any other changes, the DPV, acting on its own accord, decided to also recommend adding “suicidal thoughts and behavior” to this same section.
Relying on the DVP's report, the DDDP reached the same conclusion regarding the addition of the depression warning. But the DDDP opposed adding the suicide warning. One reviewer, Dr. Woitach, found that (i) “[t]he number of suicide ideation, attempts and completed suicide [was] lower than would be expected” in the population; (ii) “[t]he two reported cases of completed suicide contain[ed] limited information,” and one of them was “confounded with other potential life stressors”; and (iii) “[t]he relationship between depression potentially associated with Propecia and suicidality [was] difficult to assess,” including because “[p]ublications report a difference in the nature of drug-induced depression and major depression.” Dr. Woitach further concluded that, “[g]iven the few cases of completed suicide and the lack of temporal relationship with Propecia and suicide (as is seen for depression)” he did “not recommend including risk of suicide in the label at this juncture.” A second DDDP reviewer concurred with his conclusion, finding that “adding suicide to the label is [not] warranted.”
The FDA formally approved Merck's CBE supplement on March 11, 2011, without requiring additional changes. In informing Merck of the approval, the FDA did not share its underlying reports, or that it had rejected adding a warning regarding suicidality.
After Merck submitted its CBE supplement, it continued to submit PSURs. Between 2010 and 2012, it disclosed 27 additional adverse event reports related to suicidality.
Research on depression and finasteride continued to progress as well. Between July 2010 and March 2012, seven medical and scientific studies were published on the topic.[7] Shortly thereafter, in August 2012, the first study to purportedly link finasteride and suicidality was published by the Journal of Clinical Psychiatry.[8] The study was conducted between 2010 and 2011 by Dr. Michael Irwig.[9]
Irwig's study was followed in 2017 by an observational epidemiologic study designed to evaluate suicidality in men taking...
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