A recent appeals court decision has the potential to change the way in which pharmaceutical companies promote off-label uses of their prescription drugs, allowing for a more flexible approach. A Dec. 12, 2012, perspective in the New England Journal of Medicine questioned whether a host of other state and federal regulations can now withstand “such First Amendment scrutiny.”

In the Dec. 3, 2012, opinion, a three-judge panel of the U.S. Court of Appeals for the Second Circuit in New York addressed FDA regulations applicable to marketing of prescription pharmaceuticals for off-label uses. Overturning the conviction of a sales representative who was found to have engaged in off-label promotion of a prescription drug, the panel held in U.S. v. Caronia that “the government cannot prosecute pharmaceutical manufacturers and their representatives under the [Food, Drug and Cosmetic Act] for speech promoting the lawful, off-label use of an FDA-approved drug.”

In 2011, the U.S. Supreme Court held in Sorrell v. IMS Health that data mining, or the purchasing of information about prescribers from pharmacies and others and selling it to pharmaceutical companies, may be protected by the First Amendment, and the court invalidated a Vermont law that prohibited the practice, wrote Marcia M. Boumil, JD, from the department of public health and community medicine at Tufts University School of Medicine in Boston. One year prior, the Supreme Court also overturned portions of the McCain–Feingold Act, which limited the spending of tax-exempt political organizations, holding that campaign contributions may constitute commercial speech that is entitled to the protection of the First Amendment.

“Now, the Second Circuit has seized the first appellate opportunity since Sorrell to interpret that Supreme Court precedent in the context of FDA restrictions concerning off-label drug marketing,” she wrote.

Alfred Caronia, a pharmaceutical detailer, defended his off-label marketing with the argument that FDA regulations prohibiting it infringed his First Amendment right of free speech and were therefore void. “Although FDA regulations warn that it is considered ‘misbranding’ for marketers to ‘recommend or suggest’ that a drug is appropriate for an indication for which it has not specifically been approved, the FDA's authority does not extend to the practice of medicine, and thus it cannot prohibit physicians from prescribing approved drugs for non-approved uses,” explained Boumil.

In this case, a sales representative of Orphan Medical, a subsidiary of Jazz Pharmaceuticals, was assigned to promote sodium oxybate (Xyrem), a central nervous system depressant approved for the treatment of cataplexy and narcolepsy (including daytime sleepiness) in adults. It is used off-label to treat children for cataplexy and narcolepsy and to treat adults for a variety of conditions, including fibromyalgia, schizophrenia, chronic fatigue syndrome and severe cluster headaches. Caronia and a physician from Orphan gave talks and met individually with prescribers to promote Xyrem, allegedly for off-label uses, according to the case. The U.S. Department of Justice secretly recorded one such meeting, leading to the indictment of Caronia and the physician for off-label drug promotion.

Initially, a federal district court in New York found against Caronia, holding that “constraining the marketing options of manufacturers is one of the few mechanisms available to the FDA to ensure that manufacturers will not seek approval only for certain limited uses of drugs, then promote that same drug for off-label uses, effectively circumventing the FDA's new drug requirements.”

In overturning Caronia's conviction, Boumil explained that the three-judge panel of the Second Circuit said that FDA regulations were overly broad, specifically noting that nothing Caronia did constituted conspiracy to put a false or misleading or deficient label on a drug product. “The court appeared particularly persuaded by the argument that the FDA regulations allow unfettered prescribing of approved drugs for off-label uses but then, through the off-label restrictions, refuse to allow the free flow of information that would result in a full vetting of the uses, limitations and side effects of the drug,” she wrote. The Second Circuit held that such restrictions violate the principles of the First Amendment.

“Caronia and Sorrell, as well as other recent Supreme Court cases striking down governmental regulations in favor of free expression, raise significant concerns about the ability of the state and federal governments to impose a variety of regulatory programs targeting specific conduct or a particular industry,” Boumil concluded. “Indeed, the Sorrell dissent had made clear that the Court was casting a wide net—potentially broad enough to engulf the FDA's off-label regulations designed to combat false and misleading speech.”