Trial Magazine

Off-label marketing occurs when a ­drugmaker markets its drug to physicians for a use not specifically approved by the FDA. Within the bounds of medical ethics, physicians have discretion to prescribe drugs for off-label use. So what’s the harm in off-label marketing?

The primary harm stems from ­undermining the FDA’s “mission to protect and promote the public health”¹ by ensuring that a newly introduced drug is safe and effective.² To obtain FDA approval, drugmakers must conduct various trials before marketing and selling a new drug for a specific, indicated use.

But if a company has the unfettered ability to engage in off-label marketing, then what incentive does it have to conduct safety and efficacy trials to obtain approval for the drug’s additional uses? What is to stop a drug manufacturer from taking the path of least economic resistance: obtaining FDA approval for a narrow use or indication and then marketing the drug for broader uses for which there is demand? Recent court decisions ­highlight these genuine concerns, which will affect how you evaluate and plead off-label marketing claims.

The Expansion of Sorrell

For years, the FDA’s position on off-label marketing was straightforward: It was prohibited under the Federal Food, Drug, and Cosmetic Act (FDCA).³ Intuitively, this makes sense. The agency is tasked with ensuring a drug is not “misbranded,”⁴ and promoting an ­off-label use would necessarily mean the drug is misbranded. Enforcement against drugmakers for ­off-label marketing was squarely within the ­FDA’s statutory grant of authority—or so it seemed.

Enter the First Amendment. While the First Amendment provides some protection for commercial speech, the analysis balances the interests of the state actor and the commercial speaker.⁵ The FDA’s ability to restrict off-label marketing without violating the First Amendment has been challenged through a series of cases arising from the U.S. Supreme Court’s 2011 decision in Sorrell v. IMS Health Inc.⁶

Sorrell centered around a state law that dealt with the “sale, disclosure, and use of pharmacy records that reveal the prescribing practices of individual doctors” and whether this information could be “used for marketing by pharmaceutical manufacturers.”⁷ The issue in Sorrell was whether pharmaceutical sales representatives—known as “detailers”—were violating state law by using the pharmaceutical manufacturer’s purchased knowledge of a physician’s prescription practices to more effectively market brand-name drugs.⁸

While the detailers’ practices clearly appeared to violate state law, the defense asserted that the state law violated the First Amendment’s protection of commercial speech.⁹ The Court agreed, holding that “speech in aid of pharmaceutical marketing . . . is a form of expression protected by the Free Speech Clause of the First Amendment” and that the state law violated the First Amendment because it enacted “content and speaker-based restrictions.”¹⁰

In the context of Sorrell, this ­statement was not particularly troubling—the Court’s holding was squarely based on a stricter level of scrutiny reserved for situations in which the government engages in “regulation of speech because of disagreement with the message it conveys.”¹¹ The FDA’s regulation of ­off-label marketing appeared safe.

But the Sorrell holding grew more expansive. In United States v. Caronia, the Second Circuit cited Sorrell, engaged in a commercial speech analysis, and held: “We construe the misbranding provisions of the FDCA as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs.”¹² The Caronia court overturned the criminal conviction of a pharmaceutical sales representative for the off-label marketing of an ­FDA-approved drug, because the conviction violated the sales representative’s First Amendment free speech rights.¹³

In Amarin Pharma, Inc. v. U.S. Food & Drug Admin., the reach of Sorrell’s holding grew further still when the Southern District of New York held: “Where the speech at issue consists of truthful and non-misleading speech promoting the off-label use of an ­FDA-approved drug, such speech, under Caronia, cannot be the act upon which an action for misbranding is based.”¹⁴

The Amarin court granted a ­drugmaker’s request to enjoin the FDA from bringing a misbranding action—which the agency had threatened to do. The court sided with the defendant, which had argued that the FDA’s threat created a chilling effect on its constitutionally protected and truthful speech.¹⁵ In Amarin, the drug at issue was Vascepa, a “fish oil product,” that was undisputedly safe and could have been marketed as a dietary supplement.¹⁶ Regardless, the FDA argued that sanctioning off-label marketing in Amarin would result in unsafe drug practices in other cases.¹⁷ The court’s terse response to this argument was indicative of the trend that began with Sorrell: It was merely applying Caronia. “Had the FDA believed that Caronia gravely undermined the drug approval process, it should have sought review of that decision.”¹⁸

The parties in Amarin eventually settled. As part of the settlement, the FDA allowed the company to engage in truthful, non-misleading off-label promotion of its drug. This clearly contrasts with  the FDA’s prior stance that all off-label marketing was unlawful misbranding, even if the content was truthful and not misleading. Perhaps the FDA was fearful of what type of law would result from an appeal, as it likely was after the Second Circuit’s decision in Caronia. 

There is further evidence that the FDA is changing its position on off-label marketing. In early 2017, the agency released proposed industry guidance on off-label promotion¹⁹ that signaled its willingness to allow certain types of off-label promotion consistent with Amarin—that is, statements that are not “false or misleading.”²⁰

The FDA accepted public comments on the proposed guidance until April 19, 2017, and it will “continue to review its policies on firm communications about medical products.”²¹ While it appears increasingly likely that the new administration will not pursue off-label promotion claims as aggressively as the previous administration, the draft guidance has not yet been finalized and may still shift as the FDA considers public comments.

Pleading Your Claims

There has been very little judicial activity post-Amarin, and this may change only after FDA guidance. But given the rulings in Sorrell, Caronia, and Amarin—and the FDA’s apparently shifting position—what do you do when faced with a potential off-label marketing claim? First, know the limits of what you can and cannot do. The FDCA does not authorize a private cause of action for off-label marketing.²² Claims brought by private individuals must be pleaded under a state common law cause of action, state statutory provision, or a federal law other than the FDCA, such as RICO or the Lanham Act. ²³

You cannot simply copy and paste your off-label marketing claims from prior complaints. Rather, you must ­carefully vet these claims, and the ­touchstone of this analysis should be whether evidence of untruthful or misleading statements exists. You must also strategically plead these claims. Failure to do both means that the defendant may successfully challenge the complaint early in the litigation. This can have a trickle-down effect on your client’s other claims, such as failure to warn of known risks and complications.

However the off-label marketing claim is pleaded, it often takes the form of some version of the following two allegations: 

• The defendants breached their duty of care to the plaintiffs and were negligent in marketing the drug because the defendants’ sales representatives made false or misleading statements to prescribers regarding approved and unapproved uses. 
• The defendants were negligent per se because their off-label marketing constitutes misbranding under the FDCA.

These claims are often pleaded concurrently—and perhaps alternatively, as the first alleges false or misleading statements, while the second does not. Importantly, the allegation grounded in negligence per se relies on showing a pre-Amarin violation to prove the duty and breach elements of a negligence claim. Plaintiff attorneys should carefully consider whether negligence per se, in this context, remains a viable option for pleading off-label marketing claims.

So how else does Amarin affect pleading? If the plaintiff is a private individual, the defendant cannot raise a First Amendment defense—the First Amendment protects individuals or entities from state action, not private action. 

However, if you plead negligence per se or some other version of negligence without an express allegation that the defendant made false or misleading statements, the defendant can still argue that the plaintiff has failed to state a claim because truthful statements cannot form the basis of a misbranding claim under the FDCA, at least according to the Caronia and Amarin courts.²⁴ In this way, a defendant would not be arguing that a private plaintiff is infringing on its First Amendment rights. Rather, the argument goes, if the FDA cannot state a claim on the same set of facts, then neither can a private litigant. 

If you have evidence of off-label marketing but no evidence of untruthful or misleading statements in connection with the marketing, this leaves you in a conundrum. You must decide whether a good-faith basis exists for alleging that untruthful or misleading statements were made in connection with off-label marketing or whether the claim should be added through an amended complaint after discovery. 

The latter route puts you at the court’s mercy. The former carries the risk that the court, following Caronia and Amarin, will dismiss the claim. This risk is heightened if you file a consumer class action based in part on allegations of pre-Amarin misbranding to demonstrate violations of other state or federal laws. Losing this argument could result in failed class certification or outright dismissal of the complaint.²⁵

You could argue that Caronia and Amarin are non-controlling outside of the Second Circuit’s jurisdiction—or, if you’re in that jurisdiction, you could argue that those cases are limited in their holdings or otherwise distinguishable. If you are in the Second Circuit, arguing for a limited holding or attempting to distinguish these cases is an aggressive path. If you take it, consider that the drugmaker will likely assert a defense based on Caronia and Amarin. And if the defendant does, how willing are you to risk facilitating the spread of Amarin reasoning? Plaintiff attorneys need to collectively reflect on this question, as the FDA has not signaled a willingness to challenge Caronia or Amarin—and in fact, it seems to be going in the opposite direction.

If a plaintiff can present evidence that the drugmaker made untruthful or misleading statements in connection with the off-label marketing in the pleading, then Amarin will not apply, and the claim will proceed along a well-worn path. But if this evidence is lacking—and a good-faith basis for bringing the claim is not—your only practical option is to plead the off-label marketing claim in such a way that invites an ­Amarin-based defense. If you choose this path, be prepared to fight an uphill battle—with high stakes for the entire plaintiff bar.

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John R. Crone is an associate at Andrus Wagstaff in Lakewood, Colo. He can be reached at john.crone@andruswagstaff.com.

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Notes

1. Meet Stephen Ostroff, M.D., Acting Commissioner of Food and Drugs, U.S. Food & Drug Admin. (Jan. 20, 2017), www.fda.gov/AboutFDA/CentersOffices/ucm386097.htm.
2. See generally 21 U.S.C. §301 et seq. 
3. Jeanie Kim & Amy Kapczynski, Promotion of Drugs for Off-Label Uses—The U.S. Food and Drug Administration at a Crossroads, JAMA Internal Med., at E1 (Nov. 7, 2016), law.yale.edu/system/files/area/center/crit/document/viewpoint_by_jk_and_ak_in_jama.pdf. 
4. 21 U.S.C. §352 (2016); 21 C.F.R. §202.1 (2007). 
5. Cent. Hudson Gas & Elec. Corp. v. Pub. Serv. Comm’n, 447 U.S. 557, 566 (1980) (outlining a four-part test for determining whether commercial speech is protected by the First Amendment: whether the speech concerns lawful activity; whether the government’s interest is substantial; whether the regulation directly advances the asserted governmental interest; and whether the regulation is not more extensive than necessary to serve the governmental interest). 
6. 564 U.S. 552 (2011).
7. Id.
8. Id. at 557.
9. Id. at 561.
10. Id. at 557, 563. 
11. Id. at 566. 
12. 703 F.3d 149, 168 (2d Cir. 2012) (emphasis added).  
13. Id. at 152.
14. 119. F. Supp. 3d 196, 226 (S.D.N.Y. 2015) (emphasis in original).  
15. Id. at 198.
16. Id. at 237.
17. Id. 
18. Id. 
19. Medical Product Communications That Are Consistent With the FDA-Required Labeling—Questions and Answers Guidance for Industry, U.S. Food & Drug Admin. (Jan. 18, 2017), www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm537130.pdf. 
20. Id. at 2.
21. 82 Fed. Reg. 6575, 6577 (Jan. 6, 2017).  
22. See, e.g., In re Epogen & Aransep Off-Label Mktg. & Sales Practices Litig., 590 F. Supp. 2d 1282, 1287 (C.D. Cal. 2008) (“The FDCA, which grants the authority to oversee the safety of drugs, provides that ‘all such proceedings for the enforcement, or to restrain violations, of [the FDCA] shall be by and in the name of the United States.”). 
23. Id. at 1292 (“Plaintiffs’ RICO and state law causes of action, to the extent they allege fraud not dependent on the FDCA’s prohibition on off-label promotion, are valid.”). It is also worth noting that pleading claims against a drug or device manufacturer often implicates complicated federal preemption issues. These issues are outside the scope of this article. 
24. Caronia, 703 F.3d at 168–69; Amarin, 119. F. Supp. 3d at 224. 
25. See, e.g., Cent. Reg’l Emps. Benefit Fund v. Cephalon, Inc., 2009 WL 3245485, at *4 (D.N.J. Oct. 7, 2009) (dismissing the plaintiffs’ third-party payor consumer class action, in part, because “it is well established that ‘off-label marketing of an approved drug is itself not inherently fraudulent’”) (citing United States v. Caronia, 576 F. Supp. 2d 385, 397 (E.D.N.Y. 2008), rev’d on other grounds, 703 F.3d 149 (additional citations omitted)).