Hearing Debates Pros/Cons of Increased Off-label Communications
A House Energy and Commerce subcommittee heard differing opinions 7/12 on whether to advance two bills that would open up FDA’s regulatory framework to allow more dissemination of truthful and non-misleading off-label information about drugs and devices. Representing the Medical Information Working Group, Sidley Austin partner Coleen Klasmeier told the hearing that “FDA’s rules governing manufacturer communications are neither clear nor precise.” She said that “although a manufacturer is prohibited from ‘promoting’ its product for ‘new uses,’ it can lawfully provide information about off-label uses within defined circumstances. Currently there are four ‘safe harbors.’ Only one is set forth in a binding regulation; the others are in non-binding documents. They therefore lack the force of law. Moreover, two of the four safe harbors have been the subject of ongoing FDA proceedings since 2011.”
Klasmeier noted that the existing FDA regulatory scheme for such communications is unstable. “FDA and the Department of Justice aggressively pursue enforcement actions with respect to ‘off-label’ speech, but First Amendment arguments in those cases have been accepted by reviewing courts. Litigation has a destabilizing effect on the regulatory scheme and threatens FDA’s ability to make incremental changes. The public health and legal consequences of the developing case law point up the need for modifications to the existing rules and policies.”
University of Wisconsin law professor Alta Charo opposed the two bills, saying they would have the unintended consequence of undermining public health, discouraging pharmaceutical research, and setting pharmaceutical regulation back by more than 100 years. She said that history “amply demonstrates that there is compelling public interest in unbiased evaluation of evidence; in clear, accurate communication; and in maintaining incentives for research. The combined effect of these amendments is to expand promotion and payment for unproven uses of drugs. It undercuts the marketing advantages that the law uses as an incentive for sponsors to complete the research needed to see which uses are in fact safe and effective.”
Harvard Medical School Associate Professor of Medicine Aaron Kesselheim said current restrictions on off-label promotion “are not a bureaucratic or paternalistic effort to restrict manufacturers from communicating to physicians about their products. Rather, these rules were developed over the last century in response to major public health problems caused by the lack of regulation of manufacturer promotional activities.”
Kesselheim noted that recent settlements of government investigations into off-label marketing episodes have led to over $15 billion in civil and criminal fines. “In these cases, the manufacturers were not necessarily going around spreading falsehoods about their products to get physicians to prescribe them... Rather, manufacturers and their promotional salespeople might present anecdotal evidence of benefits from uncontrolled case series. Or they might show doctors the results of observational studies that actually had important design flaws not recognizable unless someone had advanced training in pharmacoepidemiology... In one study of off-label marketing practices that I led, we found that 75% of the cases involved self-serving presentations of the literature through which physicians were given unbalanced study data supporting the unapproved use. A common example was selective presentation of favorable studies, where dangers from the off-label uses allegedly being promoted were not mentioned. Other examples included presenting one drug as being superior to another when no head-to-head studies had been conducted and characterizing reports of individual cases or poorly designed studies as definitive evidence supporting an off-label use.”
Kesselheim is not keen on the bills’ requirements for certain disclosures to accompany off-label communications. “I led a systematic review of the evidence about the impact of disclaimer related to health-related claims of medical products,” he told the hearing. “Most such data has been gathered in the context of promotional statements for herbal remedies and dietary supplements, for which Congress eliminated FDA oversight of promotion more than 20 years ago in the Dietary Supplement Health and Education Act of 1994. The result has been the proliferation of untested, ineffective, and frequently unsafe products that fill store shelves and patients’ medicine cabinets and consume about $32 billion of health care resources in the U.S., often with no demonstrable benefit. Many of these products advertise health-enhancing effects and bear disclaimers that the FDA has not evaluated the promotional claims, but the mass of collected evidence reveals that such disclaimers generally fail to adequately inform or modify consumer behavior. There is no scientific basis for believing that disclaimers would function any better in this context.”
Qualchoice Health Plan Services vice president of pharmacy services Katherine Khachatourian told the hearing her organization supported the bills to relax emerging therapy information sharing between companies and population health decision makers, “who have indicated that waiting until FDA approval is often too late for the critical planning, budgeting, and forecasting associated with health benefit design.” She said there is a need for Congress to engage in this topic to create a legislative safe harbor for information sharing “so that it is clear that the proactive dissemination of certain information does not violate the prohibitions against preapproval promotion and does not run afoul of the labeling, misbranding, and intended use provisions of the Federal Food, Drug, and Cosmetic Act and its implementing regulations.”
Subcommittee chair Michael Burgess (R-TX) said that the current information sharing model is not sustainable because of differing court decisions and piecemeal guidance from FDA that leaves everyone with uncertainty. He said it was time to clarify the FDA statute and get it right on what and how information can be provided by manufacturers.
And ranking member Frank Pallone (D-NJ) said he is concerned that the bills would “severely undermine the current protections against marketing unsafe and ineffective medical products... The scientific exchange discussion draft would severely restrict the types of evidence the FDA has always relied on to determine the intended use of a medical product. It would also hamstring the agency from holding bad-actors who distribute dangerous drugs or medical devices accountable.
“The preapproval communication discussion draft,” Pallone continued, “would blow a hole in the current approval process by allowing the communication of any scientific evidence or health care economic information to payors or formularies without any recourse for the FDA to prevent bad actors from communicating false or misleading information... For example, the proposed discussion draft would allow for a manufacturer to publish a biased scientific study in any medium to constitute ‘scientific exchange.’ This could include simply posting results of a non-peer reviewed study on a company’s own website, and there is no requirement that this information be truthful.”