On March 5, FDA Commissioner Dr. Scott Gottlieb abruptly announced his resignation, effective in a month. Since then, it has been announced that Dr. Ned Sharpless, currently head of the National Cancer Institute, will replace Dr. Gottlieb on an “acting” basis. This is disturbing generally, as Dr. Gottlieb has stood out as a demonstrably competent appointee. It is also disturbing, to us, as Dr. Gottlieb leaves with a grade of “incomplete” in the area we most cared about when he was originally appointed – moving the FDA’s hidebound policy towards truthful manufacturer communications about off-label uses of FDA-regulated products into the Twenty-First Century.
Since the beginning of the Blog, we have chronicled the crumbling of the FDA’s 1950s-era ban against all truthful off-label communications in the courts, under pressure from the First Amendment. See, e.g., 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); Amarin Pharma, Inc. v. FDA, 119 F. Supp.3d 196 (S.D.N.Y. 2015).
Dr. Gottlieb was on record (something we first noticed in 2007) as opposing this prohibition, which we discussed in some depth here. Thus, we were hopeful that under Dr. Gottlieb’s leadership, the FDA would finally come around to a more nuanced – and thus more constitutional – approach to truthful off-label communications by regulated manufacturers. After all, from a public health standpoint, the current muzzling of manufacturer communications makes no sense, since anybody else in the world can post nonsense on the Internet about off-label uses, but the manufacturers, who know more about their products than anybody else, are precluded from debunking the nonsense.
There has been some progress – most notably the recent (2018) FDA recognition that regulated manufacturers could communicate with third-party payors (“TPPs”) about off-label uses and potential new products nearing FDA approval. There is now a Final FDA Guidance on this subject, “Drug and Device Manufacturer Communications With Payors, Formulary Committees, & Similar Entities − Questions & Answers, available here. Another step forward was the Agency’s 2018 shelving of a proposal to revamp its archaic “intended use” regulations for drugs (21 C.F.R. §201.128) and devices 21 C.F.R. §801.4). That proposal started out with some promise, but ended up worse than the original, when just before the change in administrations, the FDA baited and switched its stakeholders with a surprise “Final Rule” (never subjected to proper notice and comment) that would have made things worse. As we stated at the time:
The FDA’s January 9, 2017 proposal reversed course, retained knowledge of off-label use as evidence of intended use, clarified that any relevant source of evidence, whether circumstantial or direct could demonstrate intended use, and ultimately invoked the dreaded “totality of the evidence” standard. A constitutionally frail regulatory regime looked like it was about to become even worse – even more vague, over broad, and chilling.
At least Dr. Gottlieb put the kibosh on that.
But that’s pretty much it. The most critical step – recognizing that regulated manufacturers could truthfully discuss off-label uses with health care professionals (usually, but not always, doctors) at least as freely as with TPPs, hasn’t happened yet, at least with the FDA. We note that industry groups are getting tired of FDA foot-dragging on its unconstitutional position, and that truthful off-label communications with such providers have been declared “ethical” by AdvaMed, the medical device industry’s primary trade association. The pharmaceutical industry did something similar with its 2016 “Principles on Responsible Sharing of Truthful & Non-Misleading Information about Medicines with Health Care Professionals and Payers.” If the FDA itself stalls out again, we’d expect the pharmaceutical industry to press forward through its “Medical Information Working Group” and support additional court challenges to FDA restrictions on truthful off-label communications.
We were hoping that Dr. Gottlieb would, as FDA Commissioner, broker a rational, constitutional, solution out of the corner into which the Agency has painted itself. Now, unfortunately, that is not to be. Whether one views the off-label communication glass as half-full or half-empty, we’re still only halfway (if that) to an acceptable endpoint. Still, his incomplete legacy leaves the FDA off-label communication ban, if it can still be called a “ban,” in a very awkward position. Having declared that it is legal for regulated entities to provide a great deal of truthful information about off-label uses to one professional audience – third party payors – it will now be almost impossible for the FDA to justify under the First Amendment a prohibition against providing the same information in the same manner to the other equivalent audience – physicians and other professional health care providers.
We don’t know much about Dr. Sharpless. He does not have the favorable public paper trail that Dr. Gottlieb had on off-label communication issues. We are, however, pleased to read that he comes from the oncology space, and has an entrepreneurial background that includes founding a company involved in cancer treatment. We say that because, with the possible exception of pediatrics, off-label use has always been more widespread in cancer treatment than in any other area of medicine. E.g. M. Saiyed, et al., “Off‐Label Drug Use in Oncology: A Systematic Review of Literature,” 42(3) J. Clin. Pharm. & Therapeutics 251 (June 2017); M. Soares, “’Off-Label’ Indications for Oncology Drug Use & Drug Compendia: History & Current Status,” 1(3): J Oncol. Pract. 102 (Sept. 2005); J. Beck & E. Azari, “FDA, Off-Label Use, & Informed Consent: Debunking Myths & Misconceptions,” 53 Food & Drug L.J. 71, 80 (1998).
So Dr. Sharpless has been affiliated with FDA-regulated entrepreneurship in an area of medicine where off-label use has particular importance. Thus, we remain hopeful, until it is proven otherwise, that Dr. Sharpless appreciates the problems that the FDA’s attempt to prohibit truthful off-label communications cause both manufacturers trying to disseminate such off-label information and medical professionals seeking to access it. As such, we currently expect that he will follow-through and expand upon Dr. Gottlieb’s initiatives concerning off-label communications.