“How would it be protecting the public health to a greater extent by allowing such dissemination of unapproved use information while vehemently using all available resources to go after the company with the reprint that has a couple of health-related quality of life (HRQOL) claims that are just not in the label?”

I say no more.

JM

Let’s talk for a bit about the reprints we see most often. The reprints that are 98% “on-label” with the two sentences where the author embellishes the value of their research in the universe. When they happen to compare this particular study to other known studies for other products in the absence of head-to-head trials or when they decide to include a post-hoc analysis of a teeny tiny subgroup where the reliability and even importance of such analysis is dubious at best. Yes, those reprints. Are they salvageable?

I would argue that they are for a couple of different reasons. First, as you aptly point out, the reprint guidance itself was intended to cover the dissemination of medical literature concerning “off-label” uses or unapproved new uses of products which as you know is far more risky (in the grand scheme of things) than say a discussion of safety or effectiveness information for a use that has been vetted by FDA. How would it be protecting the public health to a greater extent by allowing such dissemination of unapproved use information while vehemently using all available resources to go after the company with the reprint that has a couple of health-related quality of life (HRQOL) claims that are just not in the label? To me, this would be counterintuitive and would in my mind, suppress more information than is necessary for the public good. The HRQOL reprint should receive greater protection under the First amendment in my eyes since the government interest in regulating such information on policy grounds would definitely be the lesser of the two evils. To give a free pass to the off-label folks while focusing a non-blinking eye on the 98 percenters out there would be not be a wise policy move. I do think the guidance document itself speaks far louder than the just the plain meaning of the words on the page in terms of FDA “thinking” on scientific literature. While I do not disagree with your analysis of the plain language of the guidance and therefore, by default, treatment of all “on-label” reprints as promotional labeling, I do think the FDA will exercise enforcement discretion for all peer-reviewed reprints, regardless of the use they concern. In doing so, the FDA would look to whether the reprint itself drew unsubstantiated conclusions or was overly promotional in tone and to what degree did the reprint itself concern the “unproven” claims. Was it merely ancillary or was it the primary focus of the study/analysis/reprint?

Secondly, the FDA (if they get a chance to or can figure it out) will actually consider a company’s intent (i.e., whether they took measures to not “promote” the questionable statements or claims). Such as only calling out the proven statements in a reprint carrier that a sales rep is able to speak to and balancing the reprint carrier with appropriate fair balance (risk disclosures). I cannot emphasize the last point enough since almost every reprint I have ever seen contains very little risk information and almost never addresses the warnings for a product. This would also make for an easy target for FDA and HRQOL claims would just get referenced in the enforcement action for good measure. Therefore, it would be prudent to always include the boilerplate fair balance of important safety information when disseminating reprints that would be considered promotional labeling and not covered by the guidance. The whole premise of my second rationale here is that there is, or can be, a noticeable difference between scientific exchange and promotion and the FDA can see this difference but only if you show it to them. Ok, now we are getting into the advice that I typically charge for - so I will stop here but leave you with one final thought.

If fair balance of risk information is so critically important, perhaps it would be a good idea to include this information on the cover page to append to an “off-label” reprint that is covered under the guidance? Oh hogwash, you may as well send it on a 2253 and call it promotional labeling?? A topic for another blog on another day: To 2253 or not to 2253?

M. Misocky