Regulatory Focus™ > News Articles > FDA Researchers Make Case for More Transparency When Drugs are Rejected

FDA Researchers Make Case for More Transparency When Drugs are Rejected

Posted 12 June 2015 | By Alexander Gaffney, RAC

FDA Researchers Make Case for More Transparency When Drugs are Rejected

When the US Food and Drug Administration (FDA) finds reason not to approve a drug, it issues what is known as a Complete Response Letter (CRL) indicating its reasons for withholding approval and explaining which additional data might support an approval decision. Publicly-traded companies almost always communicate the issuance of these letters to the public, and generally summarize the points made by FDA in the letter.

But how often do those companies tell the whole truth to their stockholders?

According to new research just published in the British Medical Journal (BMJ) by several FDA employees, companies have a less-than-stellar track record at giving the public an accurate assessment of the contents of the CRL, which are considered "commercially confidential" and generally not made public.

Research and Findings

The research, authored by Peter Lurie, FDA's associate commissioner for public health strategy and analysis, and five additional FDA colleagues, looked at 61 CRLs issued by FDA between 11 August 2008 and 27 June 2013.

Each CRL was broken down into a series of specific statements indicating a problem applicable to the drug application. For example, if a drugmaker was issued a CRL because FDA believed the drug was unsafe, ineffective and had manufacturing problems, the researchers would identify three specific statements.

The researchers then found press releases corresponding to the issuance of the CRLs, and compared the CRL to the press statement to determine if the content of the release matched the content of the CRL.

The research determined that just 14% of press statements matched statements offered by FDA to the company in a CRL.

"Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements," Lurie et al. wrote. "Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact."


The findings cast doubt on how reliable companies' public statements are, and whether additional transparency efforts are needed to ensure the public gets an accurate assessment of the reasons for a drug's rejection.

Lurie's research notes FDA has previously tried to change its rules to allow CRLs to be posted publicly.

"In 2009, the FDA released its transparency initiative, which aimed to provide information regarding the agency and its work to the public and regulated industry," Lurie explained. "In 2010, their transparency task force proposed that 'FDA should disclose the fact that the Agency has issued a . . . complete response letter . . . and should, at the same time, disclose the . . . complete response letter,' and sought public comment on this proposal."

Ultimately, however, industry countered that because CRLs contained confidential information about unapproved drugs, the release of the information would run afoul of legislative protections of commercially confidential information, and it would therefore be illegal for FDA to release them to the public without the express permission of each CRL owner.

Still, Lurie says, "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. It would also allow for broader and more informed public discussion by relevant stakeholders (such as patients, clinicians, researchers, and public health advocates) of the scientific and regulatory reasons for the FDA's actions."

Ultimately, Lurie concludes, there are three options. Companies could make public their CRLs. Alternatively, they could include more (and more accurate) information about the CRLs in their press releases. Or, he says, "FDA could itself make the complete response letters public, although this would likely require a change in FDA's regulations."

And, given statutory protections for commercially confidential information, that would likely mean a change in the statute as well. But given Congress' interest in FDA matters as of late (see: The 21st Century Cures Act), perhaps that's not such a farfetched idea.


BMJ Paper


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