FDA Regulation of Off-label Drug Promotion Under Attack

Abstract

IN 2005, ALFRED CARONIA WORKED AS A SALES REPRESENtative for the drugmaker Orphan Medical promoting the central nervous system depressant sodium oxybate (Xyrem), which had been approved by the US Food and Drug Administration (FDA) to treat narcolepsy. With the company’s knowledge and approval, Caronia promoted the drug to physicians for numerous unapproved (“off-label”) indications—including insomnia and fibromyalgia—and claimed the drug was safe in elderly and pediatric patients, despite warnings on the label that safety was not established in those populations. The Department of Justice investigated Caronia and Orphan Medical for violating the Food, Drug, and Cosmetic Act (FDCA). The manufacturer pleaded guilty, but Caronia did not. At trial, the government claimed that his representations to physicians effectively misbranded sodium oxybate because it was not FDA approved for the purposes he promoted. Caronia was convicted by a jury in 2008 and sentenced to probation, community service, and a $25 fine. Caronia appealed the conviction, arguing that he had been prosecuted for his speech, breaching his First Amendment rights. The government responded that it had merely used his speech as evidence of his intent to misbrand the drug— that is, Caronia’s statements showed he intended the drug to be used for purposes not described on the label. On December 3, 2012, the Second Circuit Court of Appeals sided with Caronia, overturning his conviction. In a 2-1 split decision, the court found that the prosecutors’ contention that Caronia’s promotional speech constituted misbranding and amounted to criminalizing speech. Such a restriction on speech, the court noted, would require the government to satisfy a set of rigorous conditions to justify it—a standard that many judges are now applying, even when the restriction concerns “commercial speech” like drug promotion. Citing a 2011 Supreme Court decision, the court held that heightened scrutiny was also appropriate because the FDA regulations targeted only statements with a particular content (off-label promotion) and only when disseminated by drugmakers. Under this requirement for heightened scrutiny, precedent held that if the commercial speech is “truthful and not misleading,” restricting it must serve a substantial government interest, directly and materially advance that interest, and be no broader than necessary. Focusing on the latter 2 requirements, the court found that restricting offlabel promotion does not directly advance the government’s interest in reducing unsafe drug use because it “paternalistically” blocks the “free flow of information” that could improve a physician’s off-label prescribing decisions, since it is the physician’s—not the government’s— role to determine which information is useful. Second, the court held that limiting off-label promotion is too broad an intervention, because the government could achieve its goal without inhibiting speech. Other options included educating physicians and patients “in differentiating between misleading and false promotion, exaggerations and embellishments, and truthful or non-misleading information,” affixing disclaimers to off-label uses, capping the number of off-label prescriptions a physician may write, and reminding physicians that they could be sued for malpractice if off-label prescriptions resulted in adverse outcomes. Although the 3-judge opinion is subject to review by the full Second Circuit (as well as the Supreme Court), United States v Caronia signals that courts’ evolving views of protecting corporations’ commercial speech may prove incompatible with regulating drug promotion. The nation has long put prescription drugs in a special category of commercial goods and regulated their promotion more than that of other products because unsubstantiated claims by manufacturers about their medications can result in tragic public health consequences. As a result, manufacturers cannot sell drugs without the FDA determining that their benefits outweigh their risks for their intended uses. As the dissenting judge pointed out, the United States v Caronia decision could be the first step in the judicial dismantling of the US system of drug regulation.