Off-label Promotion

Response to Califf’s Call for Off-label Code of Ethics Is on Industry’s Radar

May 30, 2017 — In response to former FDA Commissioner Robert Califf’s recent call for the Coalition for Healthcare Communication to establish a code of ethics for members, several industry leaders on the CHC’s executive committee indicated that such a code strikes a responsive chord (see related article at

At the Coalition’s May 15 Rising Leaders Conference on Healthcare Policy held in Washington, D.C., Califf raised concerns with upcoming changes in FDA off-Label communication policy likely to be formulated by the agency in response to First Amendment mandates aimed at current FDA rules and policies. Under current rules, which increasingly are being challenged in the courts, drug sponsors can only promote the approved, on-label uses of the drug while others are free to discuss and prophesize about off-label uses and doctors may use the drugs with patients as they see fit, for on- and off-label uses.

Califf clearly articulated the concern of many FDA policymakers that new policies might lead to a free-for-all in sponsor communication, in turn leading to unproven and dangerous uses. Indeed, in a Washington Post op-ed, former HHS general counsel Bill Schultz sounded a similar alarm (

Later in the Rising Leaders meeting, four CHC Executive Committee members, CHC Chairman Sharon Callahan (Omnicom Health Group), Jon Bigelow (Thayer Pond), Karsten Risch (Havas Health) and Laura Schoen (Weber Shandwick) all expressed interest in a CHC code and noted that it was currently under discussion.

For example, Schoen said that making a commitment beyond accepting legal constraints “would be a very good step for us.”  Bigelow chimed in by saying that adhering to ethical standards “is something you just have to do because it is the right thing to do” and noted several examples, including journal advertising, certified CME and medical writing.

The current standard that some at the FDA are clinging to has been discarded by a series of federal court decisions, including from the U.S. Supreme Court, leading major industry watchers and even Congressional leaders to urge the FDA to move forward to redefine the standard in a way that meets the mandates of the First Amendment and good patient care. Indeed, the existing FDA standard, essentially declaring anything beyond the label per se false and misleading, appears to be waning everywhere except for pockets of the FDA itself.

Meanwhile, Schultz, Califf and others need not fret too much about the need for an ethics code on off-label use.

The two leading biopharmaceutical organizations made a bold public statement on FDA off-label policy last August. PhRMA and BIO jumped into the vacuum to propose several new guidelines in a document called “Principles on Responsible Sharing of Truthful and Non-Misleading Information about Medicines with Health Care Professionals and Payers.” The two organizations propose a new regulatory standard that provides a great starting point for the inevitable policy debates on how the FDA defines “false and misleading” in marketing. Through and through, the PhRMA and BIO Principles call for “responsible, science-based parameters for accurate and trusted information sharing.”

Three key commitments form the basis for the new PhRMA/BIO Principles:

(1)    Commitment to science-based communication;

(2)    Commitment to provide appropriate context about data; and

(3)    Commitment to accurate representation of data.

The statement makes clear that the two associations believe that to exercise sound medical judgment in treating patients, doctors must understand the full range of treatment options, both off-label and on-label. Indeed, the data recommended by the groups to support off-label claims go well beyond existing -FDA policy for such communication, including pharmacoeconomics, usage based on real world evidence and post hoc analysis.

Specifically, Appendix A of the Principles lists the types of information about medicines that could well become part of the new standard of communication policy:

  • Data from randomized, controlled clinical trials, including those done after the drug is approved and not included in the product label.
  • Post hoc analysis, including sub-population data not analyzed as part of initial labeling.
  • Observation data and real-world evidence, including from claims data, electronic medical records, comparative effectiveness research and patient registries.
  • Pharmacoeconomic information obtained from clinical trials, observational studies, reviews of medical record databases and other predictive modeling techniques.

Although major changes are inevitably coming in the FDA’s marketing standard, the questions are when those changes will come and what they will look like. Although the FDA has promised guidance on some of these issues for at least two years, well-publicized internal struggles have delayed action.  Still, it is reasonable to guess that the FDA will start with some of the comparatively easy issues, especially more permissive rules relating to communication with payers. Payer communications have been on the forefront of FDA’s plate for some time, dating back to the 1997 passage of FDAMA 114, and few would deny that insurance companies and formulary committees are unsophisticated in their comprehension of clinical data.

The FDA communication standards already are in flux and sometime in the foreseeable future new policies will alter some of the more important communication exchanges of drug sponsors with healthcare professionals, patients and payers. Little is certain, but one thing is clear: Making more data and information available to doctors will be good for patients.