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We have been waiting, literally for years, for the FDA to revise, clarify, update, or simply pay attention to, its off-label promotion regulatory position in light of repeated governmental First Amendment losses in Sorrell v. IMS Health Inc., 564 U.S. 552 (2011); Thompson v. Western States Medical Center, 535 U.S. 357 (2002); United States v. Caronia, 703 F.3d 149 (2d Cir. 2012); and Amarin Pharma, Inc. v. FDA, 119 F. Supp.3d 196 (S.D.N.Y. 2015), to name the most notable.  The FDA has promised action on a number of occasions, but has never delivered.  This stonewalling has even caused the Pharmaceutical Research & Manufacturers of America (“PhRMA”) to force the issue by filing amicus curiae briefs in litigation, as we discussed here a couple of years ago.

The longstanding disconnect remains. What the FDA purports to prohibit, and what the First Amendment actually allows, in terms of truthful communications by regulated manufacturers about off-label uses are two very different things.  So PhRMA, joined this time by the Biotechnology Innovation Organization (“BIO”), is charging once more unto the breach, this time with its own industry-practice “principles” concerning off-label communications.  Here’s a link to the document itself, which is called “Principles on Responsible Sharing of Truthful & Non-Misleading Information about Medicines with Health Care Professionals and Payers.”  That’s a mouthful, so we’ll just call it “Industry Principles” in this post.

Essentially, these industry organizations are drawing a line in the FDA’s regulatory sand – telling the Agency, and their own members, that they will fill the gap caused by administrative dithering themselves. Notably, since PhRMA has already shown its willingness to litigate First Amendment issues against the FDA, we would not be surprised to see these guidelines form the basis of industry’s First Amendment position in future court challenges.

The Principles’ introduction first states the reason off-label communication is needed: “Scientific knowledge and new findings go far beyond . . . clinical trials, often are outside the scope of [FDA] parameters . . ., and often outdate the FDA-approved labeling.”  Industry Principles, at 1.  The introduction then explains why the industry cares so much.  “Biopharmaceutical companies are uniquely positioned to help health care professionals achieve the best outcomes for patients, because companies can provide timely, accurate, and comprehensive information about both approved and unapproved uses of [their] medications.” Id. Finally, it states what the industry is doing about it from this day forward.

These Principles are intended to form the basis for defining new and clear regulatory standards governing responsible, truthful and non-misleading communications to inform health care professionals about the safe and effective use of medicines.

Id. In other words, in default of FDA action, industry will set its own standards for off-label communications (including those that the FDA calls “promotion”), and will defend them in whatever fora are necessary, including in court.

The PhRMA and BIO standards espouse nine “principles”:

  • First: FDA regulated manufacturers should accurately communicate information based on scientifically- and statistically-sound methodologies, whether or not a labeled indication is involved − and only on that basis.
  • Second: The primary source of information continues to be a product’s FDA-approved labeling, which should be fully and fairly described. All off-label uses should be clearly identified as such.
  • Third: All off-label information requires scientific substantiation, albeit not necessarily what the FDA requires for labeled indications. The methodology behind substantiating information should be fully and fairly described, as well as any “contrary” science.
  • Fourth: More truthful scientific information available to prescribers is better than less. Caveats and “contextual information” including “different results” should be addressed through disclaimers.”
  • Fifth: All communications about scientific information should be tailored to the sophistication of the intended audience of health care providers.
  • Sixth: Scientific information from manufacturers about off-label uses is at least as valuable as information from other, mostly unregulated, sources, since manufacturers are “are expected to collect the most comprehensive and up-to-date clinical information about their medicines.” Manufacturers must be free to respond truthfully and publicly to what others say about their products.
  • Seventh: Regulated manufacturers should be able to inform medical professionals and third-party payors about new medicines and new indications that are in the regulatory pipeline, so the health care community can provide “prompt access” to these innovations upon approval.
  • Eighth: Truthful “real-world evidence,” including retrospective analyses of clinical experience (and other data described in Appendix A), should be available about all uses, whether or not on the product’s label, with the methodology of analysis clearly stated, particularly for the benefit of sophisticated third party payors.  We note that on this point, the FDA has started moving forward almost simultaneously with this 7/27/16 guidance.
  • Ninth: Truthful descriptions of information published in scientific or medical journals should be shared, in writing and orally, with the medical community, for all on- and off-label uses, without threat of FDA enforcement action. Specifically, “companies should be able to share journal articles about research that they sponsor about their own medications.” Appropriate disclosures, including “the source of funding,” should accompany the information.

Industry Principles, at 2-5.

Following these principles are fifteen factual “scenarios” illustrating the application of these industry standards in real life situations.  Id. at 7-11.  Reading these scenarios – particularly #8 – we think that there are actually ten “principles” in the PhRMA/BIO statement.  The tenth principle we derive is this:  FDA should remove itself altogether from the business of regulating purely scientific speech, such as presentations at medical conferences, because “scientific discourse . . . is not subject to these Principles and should not be regulated by the FDA.” Id. at 9.  We agree wholeheartedly.

All readers should note that these industry principles are rather unprecedented in their disregard of the FDA’s outdated regulatory scheme with respect to off-label promotion, which (at least outside of the Second Circuit) still purports to impose a flat ban on truthful off-label speech by regulated manufacturers. But then the FDA’s stonewalling on this issue, in the face of repeated adverse court decisions, is equally unprecedented.  PhRMA and BIO are in effect telling the FDA how the Agency should redo its approach off-label promotion – if the FDA wants to avoid additional legal challenges.

PhRMA and BIO are telling the FDA that facts are facts, and speakers are speakers, so that truthful presentation of scientific information should be governed by the same rules – chiefly encouraging full disclosure – regardless of the source of the information or whether the particular use at issue is on the label. That’s the line in the sand.  We also point out that these industry standards for off-label communication relate almost entirely (save for responses to public comments by others) to audiences of health care professionals.  Nobody is advocating marketing of off-label uses directly to consumers.

It will be up to all of our clients, in consultation (we assume) with counsel, to decide whether to proceed under these industry principles, or whether to continue operating in conformity with the FDA’s outdated – and we believe, unconstitutional – prohibition of virtually all truthful off-label communications. But the shot has been fired across the FDA’s bow, and we likewise assume that that their publication of these principles means that PhRMA and BIO are prepared to fight for them in court, should the FDA pursue contradictory enforcement actions.