Should Juries Try To Predict FDA Drug Labeling Decisions?
By Alan Klein and Matthew Decker
November 13, 2018
On June 28, 2018, the Supreme Court of the United States accepted for review Merck Sharp & Dohme Corp. v. Albrecht, an appeal from the Third Circuit Court of Appeals’ decision in In re Fosamax (Alendronate Sodium) Products Liability Litigation. At the marrow of the high court’s review lie the thorny questions of whether a state law failure-to-warn claim is preempted where the U.S. Food and Drug Administration has rejected a drug manufacturer’s proposed label warning about the health risks at issue, and, in making this determination, whether a jury, as opposed to the trial court, may be asked to look beyond the FDA’s rejection and decide if the FDA would have approved a differently worded warning had it been proposed by the manufacturer.
While the issue is a relatively narrow one, the Supreme Court’s analysis promises to shape the way courts around the country decide whether and how the decisions of regulatory agencies should be interpreted ― and here, predicted ― by juries.
How Did We Get Here?
The Fosamax litigation began in 2011, when the Judicial Panel on Multidistrict Litigation consolidated several thousand lawsuits in the United States District Court for the District of New Jersey. The common question raised by the plaintiffs was whether their use of Fosamax, a drug developed and manufactured by Merck for the treatment and prevention of osteoporosis, led to femur fractures and similar bone injuries, and further, whether Merck had properly warned of these potential risks.
From the outset, Merck maintained that the failure-to-warn claims were preempted under the supremacy clause of the U.S. Constitution, because the FDA had previously rejected Merck’s proposed revision of the Fosamax label to advise prescribing physicians of the risk of femoral fractures. Merck filed for summary judgment on preemption grounds, and after a bellwether trial was completed, the district court granted the motion, reasoning, “clear evidence existed that the FDA would not have approved a stronger warning to the Fosamax label as of the date of [plaintiff’s] injury.”
The court subsequently extended this ruling beyond the bellwether case to dismiss all claims similarly preempted by the FDA’s rejection of Merck’s proposed label changes.
Fosamax in the Third Circuit
Ultimately, the dismissal of these cases and the preemption issue was appealed to the Third Circuit, which considered not only what constitutes “clear evidence” of the FDA’s rejection of a proposed warning, but also whether the issue presents a question of law, a question of fact for a jury to decide or a mixed question of fact and law for the court to resolve.
In its opinion, the Third Circuit concluded first that the “clear evidence” standard articulated by the Supreme Court in its seminal Wyeth v. Levine decision imposes a high burden on drug manufacturers seeking preemption, one that surpasses the preponderance-of-the-evidence standard generally applied in civil cases. Second, the Third Circuit reversed the district court’s dismissal of the Fosamax cases, concluding that the question of what the FDA might have done with a differently worded warning, had it been proposed, constituted a question of fact for a jury to decide. This ruling prompted Merck to appeal to the Supreme Court.
Setting the Scene: Wyeth v. Levine
Before we address how the Supreme Court may react to the Third Circuit’s decision, it may be useful to consider the earlier case in which the high court established the “clear evidence” hurdle for drug manufacturers seeking to invoke federal preemption in pharma products liability cases.
In Wyeth, Diana Levine brought a state law failure-to-warn claim alleging that Wyeth did not sufficiently label the risk of gangrene infection when its anti-nausea medication, Phenergan, was administered by injection. In its defense, Wyeth argued that the claim was preempted because the FDA had approved its label and any unilateral action to modify that label would have violated FDA regulations — rendering it impossible to warn the prescribing physician of serious risks from one of the prescribed methods of the drug’s administration.
Justice John Paul Stevens, in an opinion joined by Justices Anthony Kennedy, David Souter, Ruth Bader Ginsburg and Stephen Breyer, and concurred in by Justice Breyer, and by Justice Clarence Thomas in judgment only, concluded that Levine’s state law tort claim was not preempted. In so ruling, the court emphasized that manufacturers, not the FDA, bear primary responsibility for updating their products’ labeling. Thus, “absent clear evidence that the FDA would not have approved a change to” the label in question, preemption is unavailable to preclude failure-to-warn claims (emphasis added).
In reaching this conclusion, the court did not address whether this inquiry into the FDA’s decision-making process should be considered by courts as a question of law or by juries as a question of fact. To that end, Justice Samuel Alito, joined by Justice Antonin Scalia and Chief Justice John Roberts, dissented, at least in part, on the ground that juries should not be permitted to usurp the specialized regulatory expertise and responsibilities of the FDA.
A Closer Look at Fosamax
With an understanding of the Supreme Court’s end point in Wyeth, we can begin to fathom how the Third Circuit framed its conclusions in Fosamax ― and where it may have gone astray.
Permitting Jurors to Surmise FDA Action
The flaw in the Third Circuit’s consideration of agency action is captured in contextualizing the preemption issue as “whether the FDA would have approved a different label amendment.” In committing the answer to this question to a jury, the circuit court tasked these fact-finders “to discern what … the FDA’s likely response [would be] to a differently worded [labeling] proposal.” Conceding that the jury’s “assessment is certainly complex,” the court nonetheless eschewed the necessity for “any special legal competence or training.” 
To prevail on a preemption defense, and in the absence of a “smoking gun” or flat-out FDA rejection of the proposed warning (which may be suitable for summary judgment consideration), the court held a defendant would need to demonstrate to a jury’s satisfaction that it was “highly probable that the FDA would not have approved a label change.”
But allowing a jury to postulate what a federal agency might have done in a counterfactual situation if presented with a nonexistent drug labeling proposal does not square with Supreme Court precedent prohibiting such a “mouse trap game,” in which factfinders are permitted to speculate on “possible actions by the FDA and the brand-name [drug] manufacturer.” A jury cannot build a better mousetrap in the form of a stronger warning label by conjecturing if, when presented with a differently worded warning than the one that the manufacturer proposed, the FDA would have approved or rejected it.
Reliance on Inapposite Case Law
In support of its holding that juries decide the preemption issue, the Third Circuit relied upon decisions in other preemption cases that are distinguishable from the Fosamax case.
In Boyle v. United Technologies Corp., concerning application of the government contractor defense in a military helicopter fatal accident case, the Supreme Court addressed the discretionary function exception to the Federal Tort Claims Act in determining when state tort law needs to be displaced by the overriding objectives of federal legislation.
The court held that state law must be displaced for state law design defect tort claims involving military equipment where the government agency has established reasonably precise specifications, the equipment conformed to those specifications and the supplier warned the government of dangers in the use of the equipment that were known to the manufacturer but not the government. These factual determinations were deemed appropriate for a jury’s consideration, as they did not involve any “second guessing” of the military agency decision approving equipment design and specifications.
A second case cited by the Third Circuit, MD Mall Associates LLC v. CSX Transportation Inc., addressed the effect of both express and implied preemption under the Federal Railroad Safety Act. Finding no express preemption of the plaintiff’s claim that a railroad’s allowance of storm water intruding onto the plaintiff’s property may warrant injunctive relief, the Third Circuit remanded the case for further factual findings on the implied preemption issue. At no point in the decision, however, was any consideration given to whether the inquiry was one suitable for a jury’s determination as opposed to a court’s.
The FDA’s Subsequent Approval of Merck’s Label Change Does Not Assist Plaintiffs in Fosamax
One of the more troubling aspects of the reversal of the district court in Fosamax is that Merck went to great lengths to amend the Fosamax label, and these efforts were rebuffed by the FDA before the labeling was changed by the FDA to reflect the risk of femur fractures. In September 2008, Merck asked the FDA to supplement Fosamax’s label to warn of low-energy “stress fractures.”
In May 2009, the FDA issued a complete response letter to Merck, approving Merck’s proposed changes to the “Adverse Reactions” portion of the Fosamax label, while rejecting Merck’s proposed changes to the “Warnings and Precautions” section of the label. It was not until October 2010, after additional research, that the FDA required manufacturers of this class of medications to amend the “Warnings and Precautions” portions of their labels to warn of the risk of atypical femoral fractures. Merck complied, submitting the label changes to the FDA, which were approved and added to the Fosamax label in January 2011.
Unlike the defendant in Wyeth, which failed to seek FDA approval to eliminate from Phenergan’s labeling a method of administration posing the greatest risk of gangrene, Merck’s attempts to strengthen Fosamax’s label were proposed and rejected. To skirt this seemingly dispositive evidence, however, the plaintiffs in Fosamax parsed words, arguing that Merck’s proposals were rejected because of their mention of “stress fractures” as opposed to the “atypical femoral fracture” language ultimately adopted by the FDA.
The district court in Fosamax shut the door on this approach as improperly speculative. But the Third Circuit disagreed, finding that the FDA’s rejection of Merck’s proposed label change did not satisfy Wyeth’s “clear evidence” standard — and that a jury should be permitted to consider evidence of alternatively worded proposals Merck could have made, but didn’t.
The Future of the Wyeth v. Levine Preemption Defense in Pharma Cases
Fosamax presents a unique opportunity for the Supreme Court to clarify some of the bedrock principles of preemption law by articulating what is meant by “clear evidence” of the FDA’s actual or predicted rejection of what a plaintiff suggests are adequate drug warnings of potential health risks.
The court may also use Fosamax to decide whether, as in Daubert and Markman, courts are better equipped to decide such issues. In light of prior preemption precedents and the current composition of the Supreme Court, we predict reversal of the Third Circuit in a thoughtful reanalysis of Wyeth v. Levine to guide practitioners and courts in applying its preemption criteria.
Disclosure: Duane Morris represented CSX in MD Mall Associates LLC v. CSX Transportation Inc., discussed in this article, once this case was remanded from the Third Circuit, through trial. The case is now on its second Third Circuit appeal with plaintiff MD Mall appealing, and Duane Morris is counsel on the appeal. Additionally, Duane Morris was counsel for the petitioners in Markman v. Westview Instruments Inc., also discussed in this article.
- In re Fosamax (Alendronate Sodium): Prod. Liab. Litig., No. 08-08 JAP LHG, 2014 WL 1266994, at *2 (D.N.J. Mar. 26, 2014), vacated, 852 F.3d 268 (3d Cir. 2017).
- 555 U.S. 555 (2009).
- In re Fosamax (Alendronate Sodium) Prod. Liab. Litig., 852 F.3d at 293, cert. granted sub nom. Merck Sharp & Dohme Corp v. Albrecht, 138 S. Ct. 2705 (2018).
- Wyeth v. Levine, 555 U.S. at 571.
- Wyeth, 555 U.S. at 606 (Alito, Scalia, J.J., and Roberts, C.J., dissenting) (reasoning that “turning a common-law tort suit into a ‘frontal assault’ on the FDA's regulatory regime for drug labeling upsets the well-settled meaning of the Supremacy Clause and our conflict pre-emption jurisprudence”).
- In re Fosamax (Alendronate Sodium) Prod. Liab. Litig., 852 F.3d at 292.
- Id. at 293.
- Pliva Inc. v. Mensing, 564 U.S. 604, 619-20 (2011).
- Id. at 620-21.
- 487 U.S. 500 (1988).
- Id. at 512.
- See id. at 514 (“[W]hether the facts establish the conditions for the defense is a question for the jury”).
- MD Mall Associates LLC v. CSX Transportation Inc., 715 F.3d 479 (3d Cir. 2013). Disclosure: Duane Morris represented CSX once this case was remanded from the Third Circuit, through trial. The case is now on its second Third Circuit appeal with Plaintiff/MD Mall appealing. Duane Morris is counsel on the appeal.
- In re Fosamax (Alendronate Sodium) Prod. Liab. Litig., 852 F.3d at 276-77.
- In re Fosamax, 2014 WL 1266994, at * 9 (D.N.J. Mar. 26, 2014), vacated, 852 F.3d 268 (3d Cir. 2017) (“Thus, any expert testimony relating to what Merck could have or should have done, and what the FDA would have done in response to the same, is purely speculation and does not rise to the level of being a genuine fact dispute”).
- Daubert v. Merrell Dow Pharmaceuticals Inc., 509 U.S. 579 (1993) (expert witnesses); Markman v. Westview Instruments Inc., 517 U.S. 370 (1996) (patent claim construction). Disclosure: Duane Morris was counsel for the petitioners in Markman.
Reprinted with permission of Law360.