Don’t Cave on Off-label Speech: Professors to FDA
University of Arizona/New York University law school professor Christopher Robertson and Harvard Medical School professor Aaron Kesselheim are urging FDA to stand firm against court decisions on off-label promotion that could lead the agency away from its mission to approve regulated products based solely on scientific evidence. Writing in a New England Journal of Medicine Perspective column, the two say the “U.S. constitution should not be misconstrued in such a way as to undermine the primary functions of federal regulation in this area: to protect patients and to create a high quality market for drugs and devices that is driven by science rather than hype.”
They note that while off-label use is common, especially in oncology, where it can be considered the standard of care, surveys have revealed that supporting evidence is lacking for many off-label uses. Referring to a 2nd Circuit Court of Appeals decision in 2014 that held that sales pitches by pharmaceutical sales representative Alfred Caronia were protected commercial speech under the First Amendment, Robertson and Kesselheim say that the uses for Jazz Pharmaceuticals’ Xyrem (sodium oxybate) promoted by Caronia “were not based on high quality data and were likely to cause patients substantial harm….”
“The Caronia decision subverted decades of presumptions about how the government could oversee the behavior of the pharmaceutical and medical device industries,” the article says. “For over 50 years, the Federal Food, Drug, and Cosmetic Act has required that drugs (and later, high-risk devices) be labeled for all uses intended by their manufacturers and that their safety and efficacy for these uses be first demonstrated in clinical trials. FDA created ‘safe harbors’ allowing companies to distribute peer-reviewed literature or answer physician questions. However, until the 2nd Circuit’s Caronia decision, if a company promoted intended uses that had not been FDA-approved, that promotion would be clear evidence that the product was misbranded and that its sale for those uses was illegal. The fact that the work of the pharmaceutical sales representatives involved speech did not matter before Caronia.”
The article also cites two later 2nd Circuit decisions that followed the precedent set in Caronia. There is also a case that will be heard in the 1st Circuit. Robertson and Kesselheim say they believe that the 1st Circuit and other courts should reject Caronia on its merits. The more important question, they write, is whether FDA or the courts should evaluate product claims.
“Congress established FDA’s premarketing approval process to channel claims about safety and efficacy into an expert agency, where the claims can be evaluated rigorously and independently on the basis of submitted evidence,” they say. “The process thus creates an incentive for companies to undertake the scientific research that is required for FDA approval, an incentive that applies to both original intended uses and new uses. In fact, about half of FDA’s approvals each year are for new uses of previously approved drugs, which turn off-label uses into on-label ones. This gateway function remains a key way of ensuring that health care is based on robust science, so that patients are protected and wasteful spending is minimized.”
According to the authors, drug and biologic companies sense that the time may be ripe for a major policy shift and have released proposed new guidelines calling for a rollback of FDA regulation so they can “responsibly” promote new uses to doctors, even beyond the FDA safe harbors. “We fear that these developments could be the beginning of an FDA retreat from the act’s fundamental precepts, which require that basic standards for proof of safety and efficacy be met for every intended use of a drug or high-risk medical device,” they conclude. “Rather than acceding to the views of two judges in one federal circuit, we hope that FDA continues to stand on principle.”