By Clinical Informatics News Staff 

June 15, 2015 | Pharmaceutical companies in the U.S. have long maintained that “complete response letters” — letters from the FDA rejecting a drug or medical device submitted for approval — are part of the confidential application process and should not be made public unless the sponsor chooses to release them. As a result, the public rarely sees the FDA’s own explanation for rejecting a product, or its advice for running new trials that would clear up any outstanding issues — a sharp contrast from the European Medicines Agency, which is mandated to publish this information.

Last week in the BMJ, members of the FDA’s Office of Public Health Strategy and Analysis published a study trying to assess the effects of this policy. The authors compared the content (still kept confidential) of 61 complete response letters the FDA issued between August of 2008 and June of 2013, with all related press releases issued by the subjects of those letters. The study may be a preamble to a reassessment of FDA policies on sharing the reasons for rejecting drug candidates.

According to the study, the differences between complete response letters, and press releases based on those letters, are stark and go well beyond omitting minor details for the sake of brevity.

To better quantify areas where press releases agreed or disagreed with the FDA’s own statements, the authors divided each press release and complete response letter into “statements” describing some reason a product was not approved, which could address areas like a drug’s safety, its efficacy, or concerns about its chemistry or manufacturing processes. Even in the most important of these areas, safety and efficacy, only around 15% of statements in complete response letters were “matched” by corresponding statements in press releases. More than one in five press releases had no statements that matched the relevant complete response letters at all. For another 18% of complete response letters, no press release was ever issued.

In fact, the median number of statements in a press release that matched a statement in the FDA’s complete response letter was just one. The FDA statements most likely to be conveyed to the public were recommendations of new trials, which made it into press releases more than half the time — perhaps not surprising, as this paints a rejection in a slightly more positive light, allowing companies to say they have a clear path forward with a rejected product.

Perhaps most egregious was the case of seven complete response letters that rejected drugs because patients treated with these therapies died at a higher rate than patients in control groups. In only one case did that information make it into a press release. 

All this information remains confidential; we have no way of knowing, for instance, which six drugs evaluated in the period of this study led to higher mortality rates that were never reported to the public, unless the sponsors of those trials at some point decide to release the full content of the letters they received. The FDA Office of Public Health Strategy and Analysis will now have to decide whether its findings warrant some change in policy.

The authors’ sympathies seem clear. “Disclosure of letters would allow the FDA to increase the overall transparency of its regulatory processes, providing greater awareness of the agency’s role in protecting health and combating misperceptions regarding the basis for non-approval of a drug,” they write. “It would also allow for broader and more informed public discussion by relevant stakeholders… of the scientific and regulatory reasons for the FDA’s actions.”