New Strategies Needed to Clarify Off-Label Marketing

Litigation, high court decisions and the internet have altered the landscape for exchange of information on drugs and medical products, but the FDA has not kept pace in updating its rules governing what marketers can say about their therapies. Despite considerable pressure to address these issues, FDA has yet to issue new guidance or to hold a public meeting on the subject, something that top officials said they would do more than a year ago. The result is inconsistent policies that lead manufacturers to seek clarification in the courts.

Perhaps an outside advisory panel should vet off-label communication issues? Or FDA should add more “low-tier” evidence to approved product labels? Those proposals come from a stakeholder working group headed by Mark McClellan, now director of the Duke-Margolis Center for Health Policy. Last month, the group issued a white paper on “Policy Options for Off-Label Communication” that maps out current problems and policy options for obtaining better information to improve patient care [see here].

At a recent briefing, lawyers, health professionals and patient representatives described how the health care landscape has changed in the decades since FDA established its rules governing what manufacturers can say about regulated products. Even those skeptical of the idea for an independent off-label-use panel supported the call for new approaches to end the “current cycle of litigation” that diminishes FDA’s authority over promotion of drugs and medical devices.

An easy recommendation is for FDA to clarify its current off-label communication policy and to better define the terms “labeling,” “scientific exchange” and “intended use” in the context of the off-label use landscape. Also helpful would be an FDA web site that serves as a central repository for documents, guidances and other information on this topic to reduce confusion and disagreement over what current FDA policies actually are.

More difficult is the proposal to ensure consistent enforcement of off-label communication policy within FDA and across federal and state agencies including the Department of Justice, the Federal Trade Commission and the Office of the Inspector General. Industry considers this critical to support “safe harbor” provisions related to communications, which is needed for sponsors to invest in further evidence development.

A significant change would revise FDA-approved labeling to include information based on lower level “tiers” of supporting evidence, which could be communicated “within certain circumstances or to particular audiences.” FDA-supported pilot programs would test processes for adding modifications or additional efficacy claims to the label, or whether FDA’s Sentinel System could help develop evidence on a new indication or to evaluate the use of claims in value-based payment models that reimburse sponsors based on impact on patient health.

The most contentious proposal is to establish an entity outside FDA to accredit certain types of communication. It would review sponsor evidence associated with off-label use, rank such evidence, and possibly set timeframes for a sponsor to develop further information to support the additional use. The working group cited precedents for third-party advisory boards to tackle advertising and communication issues and to offer recommendations to federal agencies.

Not everyone in the working group supports third-party review or all the strategies outlined in the white paper. At the briefing, Josh Sharfstein, associate dean of the Johns Hopkins School of Public Health and former FDA deputy commissioner, opposed having an outside panel “calling balls and strikes” for FDA. He said that adding an extra section to product labels is “practically impossible,” and that there is strong evidence that off-label communication leads to abuse, higher costs, and companies “stretching the truth.”

Conversely, Peter Pitts, head of the Center for Medicine in the Public Interest, backed the call for “bold action” to implement the group’s proposals. The strategy for third-party sanctioned communication will support well-informed clinical decision-making, he said, reduce inconsistencies in enforcement actions, promote evidence development, and avoid “continued cycles of litigation.”

Meanwhile, the legal fight continues. Just last week, a federal jury in Texas decided that a medical device maker, Vascular Solutions, did not violate federal law in distributing off-label – but truthful – information on its products. That ruling lines up with other key decisions on this topic. FDA lawyers seem to agree that it’s not illegal for a marketer to provide physicians with “wholly truthful and non-misleading information”  on unapproved product uses [see FDA law blog, Feb. 26, 2016]. So maybe it’s time for a new approach to vetting off-label information and clarifying related issues.