Prospects for Regulation of Off-Label Drug Promotion in an Era of Expanding Commercial Speech Protection

62 Pages Posted: 20 Mar 2014

See all articles by Aaron S. Kesselheim

Aaron S. Kesselheim

Brigham and Women's Hospital/Harvard Medical School

Michelle M. Mello

Stanford Law School; Department of Medicine

Date Written: March 18, 2014


On December 3, 2012, the United States Court of Appeals for the Second Circuit handed the government yet another setback in its quest to stem the deleterious public health effects of aggressive pharmaceutical marketing. United States v. Caronia involved a First Amendment challenge to a pharmaceutical sales representatives’ criminal misdemeanor prosecution for promoting the narcolepsy drug Xyrem for multiple off-label uses by making oral statements about uses of the drug not approved by the Food and Drug Administration ("FDA") during sales calls to a physician’s office. On the basis of evidence about his statements presented at trial, the representative, Alfred Caronia, was convicted of conspiracy to introduce a misbranded drug into interstate commerce. In a 2-1 decision, the Second Circuit held that the government had prosecuted Caronia because he engaged in constitutionally protected commercial speech, in violation of his First Amendment rights. In this Article, we review the implications of the Caronia decision for the FDA’s ability to regulate off-label promotion and set it in the context of other major court decisions concerning the scope of First Amendment protection for commercial speech concerning pharmaceuticals. After summarizing the statutory and regulatory framework governing off-label promotional communications, we review relevant precedent and the Caronia decision. Considering both the Caronia case and other precedents, we then consider what avenues remain for FDA regulation of off-label promotion by pharmaceutical manufacturers. We discuss five potential strategies. The first three revolve around key technical issues arising from Caronia: ensuring that prosecutions are based on written rather than oral statements, emphasizing that speech is being used as evidence of intent, and focusing on the false or misleading nature of the promotional materials. The fourth involves a frontal challenge to the Second Circuit panel’s decision in Caronia — we suggest ways in which the government could make a stronger case that its regulatory framework for off-label promotion satisfies the criteria of the Central Hudson test. Finally, we consider alternative regulatory regimes for off-label promotion, such as limited approvals of off-label indications paired with limits on prescribing and accelerated supplemental FDA approval for promotion of unapproved uses. These options may be useful if the government has to intervene to prevent the substantial public health risks of unfettered off-label promotion that may emerge in a post-Caronia world.

Keywords: FDA, regulation, commercial speech, First Amendment, off-label, prescription drug

Suggested Citation

Kesselheim, Aaron S. and Mello, Michelle M., Prospects for Regulation of Off-Label Drug Promotion in an Era of Expanding Commercial Speech Protection (March 18, 2014). North Carolina Law Review, Vol. 92, 2014, Available at SSRN:

Aaron S. Kesselheim (Contact Author)

Brigham and Women's Hospital/Harvard Medical School ( email )

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Michelle M. Mello

Stanford Law School ( email )

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Department of Medicine ( email )

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