The ability of physicians to prescribe approved medicines for purposes not sanctioned by the Food and Drug Administration (FDA) is one of the most important elements of medical care in the United States. These “off-label” uses are perfectly legal, and doctors rely on them extensively. But the agency views off-label prescribing as an attempt to circumvent its control over the nation’s pharmaceutical supply, so a number of regulations make it difficult for doctors to learn about and prescribe drugs off-label.
The most prominent rule entirely forbids drug manufacturers from promoting off-label uses. That might change soon, however, because two different federal courts are now considering lawsuits challenging the constitutionality of the off-label promotion ban. And given a string of recent Supreme Court cases affirming commercial free speech rights, one of those cases may at least partially invalidate the FDA’s restrictions.
Before a drug can be sold in the United States, it must be certified by the FDA as safe and effective for a specific, or “on-label,” use. However, once a drug is approved, physicians may legally prescribe it for any other purpose. And because medical research regularly discovers new treatment options years before the FDA can approve them, off-label prescribing enables patients to benefit from the most up-to-date knowledge.
The practice is ubiquitous in cancer treatment, cardiology, and neurology, and by some estimates, at least 20 percent of all prescriptions written are off-label. The American Medical Association says that many off-label uses are considered “reasonable and necessary medical care, irrespective of labeling.” In fact, doctors can be subject to malpractice liability if they do not use drugs for off-label indications when doing so constitutes the standard of care. That’s one reason most private health insurance plans with prescription drug benefits cover various off-label uses, as do Medicare and Medicaid.
The FDA acknowledges this in theory. According to the agency's website, "Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment.” But the FDA doesn’t make it easy for doctors or patients to learn about new off-label uses.
Doctors learn about some off-label uses in medical school, and later by reading medical journals articles or hearing about them from colleagues or at conferences. But the FDA uses its authority over drug labeling and “promotion” (which includes not just advertising but virtually any communication with health professionals or patients) to prevent manufacturers from disseminating information about off-label uses, even to doctors.
Drug makers may engage in a limited range of so-called educational activities, such as speaking about research on off-label uses at medical conferences. And in some circumstances, they may send peer-reviewed medical journal articles and excerpts from medical textbooks to physicians – but not if the firm has any financial ties to the underlying research. Almost everything else is forbidden, though the regulations are so unclear that even experts cannot always tell what is permitted.
National surveys commissioned by the Competitive Enterprise Institute found that a large majority of physician specialists believe the FDA’s policies have made it more difficult for them to learn about new uses, and that the agency should not restrict information about off-label use. Nevertheless, the FDA and federal prosecutors regularly hit violators with both civil and criminal sanctions. Just last month, drug maker GlaxoSmithKline pled guilty and paid a record $3 billion to settle allegations that it illegally promoted several of its products for off-label uses. Similarly, Merck agreed to pay $950 million to settle claims that it illegally promoted Vioxx off-label.
But it isn’t just big manufacturers that have been targeted. In January 2010, the FDA threatened to prosecute a Florida dermatologist for mentioning in interviews with Elle and Allure magazines and on NBC’s Today show that an anti-wrinkle drug she was testing had shown positive results and that “early data shows it may last longer and kick in faster than Botox.”
The FDA’s aggressive enforcement has attracted the attention of constitutional scholars who argue that restrictions on truthful and non-misleading speech violate the First Amendment. Well-established case law holds that government may not categorically bar truthful and non-misleading speech simply because its purpose is to promote a commercial transaction. Instead, the government must have a substantial interest in regulating the speech in question, and the regulation must directly advance that governmental interest and be no more extensive than necessary.
The agency and its supporters say the ban prevents snake oil salesmen from peddling unproven fixes, and the courts agree that preventing false or fraudulent speech is a substantial governmental interest. But the rules do not merely forbid false or misleading claims; they ban all promotion of off-label uses, even if they have been proven to be safe and effective in clinical trials.
Over the past decade, a handful of challenges have been brought in federal courts, with limited success. But none has resulted in an unambiguous ruling that the restrictions are unconstitutional.
Prior to 1999, for example, FDA regulations prohibited even the distribution of peer-reviewed medical studies unless the manufacturer had already submitted a supplemental application for approval of the off-label use in question. But in a case brought by the nonprofit Washington Legal Foundation, a federal district court held that a ban on disseminating truthful and non-misleading information contained in medical journal articles was unconstitutional.
On appeal, the FDA tweaked its interpretation of the law and claimed the rules governing journal articles merely established a “safe harbor” under which manufacturers would be automatically deemed in compliance. The regulations did not prevent all off-label promotion, according to agency lawyers. And they conceded that drug manufacturers do have some First Amendment rights, including the right to distribute journal reprints. That rendered the constitutional question moot. But in the intervening years, the FDA has declined to say what else is permitted.
The U.S. 2nd Circuit Court of Appeals in New York and the U.S. District Court for Washington, D.C. will each have an opportunity to shed some light on the matter in the coming months.