Earlier this month the Food and Drug Administration reached a settlement with Amarin, a small pharmaceutical firm, allowing it to promote its drug Vascepa for treatments that the agency had not specifically approved. The company had sued the FDA, claiming a First Amendment right to “engage in truthful and non-misleading speech.” The agency maintained that the settlement was “specific to this particular case and situation.” In reality, it is a watershed that could fundamentally change the way drug companies market their products.
It is legal for physicians and other health-care providers to prescribe drugs for uses that the FDA has not specifically approved. The agency acknowledges that so-called off-label uses are medically appropriate—but has long banned companies from encouraging or advertising these uses among physicians or consumers. And so the anomaly: Off-label use is legal, but promoting off-label use is not.
In 2012, however, the federal Court of Appeals for the Second Circuit struck down the conviction of a pharmaceutical salesman for promoting Xyrem (originally produced by Orphan Medical) as a treatment for fibromyalgia and insomnia, although the FDA approved it only for narcolepsy. In U.S. v. Coronia, the court ruled, on First Amendment grounds, that “the government cannot prosecute pharmaceutical manufacturers and their representatives under the F.D.C.A. [Food, Drug and Cosmetic Act] for speech promoting the lawful, off-label use of an F.D.A.-approved drug.”
The agency said that this setback would not significantly affect its ability to ban off-label promotion. But it also declined to appeal the ruling to the Supreme Court.
And now it has settled with Amarin on Vascepa, which was approved for use in patients with severely elevated triglyceride levels (greater than 500 mg per deciliter). The company had been disseminating published papers that demonstrated—on the basis of multiple large clinical studies—that the fish-oil-derived drug was also effective, in combination with statins, for reducing triglyceride in patients whose levels were above 200 mg/dL.
More court cases undoubtedly will be coming if the FDA does not take the lead in ironing out a better policy about promoting off-label uses of approved drugs, consistent with the First Amendment. If it doesn’t, the courts will.
One “solution” would be to outlaw off-label use altogether, after which questions about off-label promotion would be moot. The FDA could get cover for this regulation from a 2001 study that showed 73% of off-label drug mentions had little or no scientific support.
Such a diktat would be dangerous. The same study showed that 21% of the 150 million prescriptions in 2001 were for off-label uses, the most common of which were as anti-seizure medicines and for cardiac diseases. Moreover, a 2008 study found that eight out of 10 cancer doctors surveyed had prescribed drugs off-label. For cancer, on-label use amounted to 70%, and off-label use amounted to 30%.
Off-label treatments were ordered for 96% of all pediatric patients, and 100% of patients ages 13-17 in the intensive care unit. A 2011 study of medication orders for 414 patients in 37 intensive care units across nation showed that more than 35% were for an off-label purpose and that 97% of patients received at least one off-label medication.
Many effective treatments have been discovered through the off-label use of drugs. For example, beta-blockers, originally approved for hypertension, were shown to be effective in patients with heart failure. Spironolactone, approved as a diuretic, is used for female pattern baldness and also for acne.
Here is a far better path forward. FDA approval means that a vast safety database already has been amassed showing substantial evidence of effectiveness for the on-label use for the drug in question. But off-label use—especially in the context of clinical studies or clinical experience—is medically rational and appropriate. The FDA should permit the dissemination of this clinical information by applying a standard akin to the Federal Trade Commission’s “competent and reliable scientific evidence” requirement, as opposed to the agency’s “substantial evidence” standard that the agency uses to initially approve the drug.
Here’s how this approach might work: An advertiser of an off-label use for an approved drug would have to possess at least the level of substantiation expressly or implicitly claimed in the advertisement: “Tests Prove . . . ” “Doctors Recommend . . . ” “Studies Show . . . ”
The level of substantiation depends on what is being claimed. For example, if the stated off-label use is to prevent heart attacks, data showing that patients taking the drug had fewer myocardial infarctions would be required, not merely fewer episodes of chest pain. Moreover, a national database showing the results of off-label clinical studies would help patients and physicians make informed decisions, while enabling the FDA to ensure the proper dissemination of truthful and non-misleading information.
Dr. Gulfo is the executive director of the Rothman Institute of Innovation and Entrepreneurship at Fairleigh Dickinson University and author of “Innovation Breakdown: How the FDA and Wall Street Cripple Medical Advances” (Post Hill Press, 2014).
This article originally appeared on www.wsj.com on March 27, 2016.