FDA's use of adcomms prior to drug approval decreased over the last decade

Regulatory NewsRegulatory News | 03 May 2022 |  By 

Between 2011 and 2021, the US Food and Drug Administration (FDA) decreased the use of advisory committees before approving drugs from 59% to 6% per year, according to recent research published in Health Affairs.
“Advisory committees, if used consistently, can lend credibility to the FDA’s decision to allow a drug to market. But the decrease we found in advisory committee review of approved drugs since 2010 presents concerns about how FDA is choosing to use—or not use—independent expert advice,” C. Joseph Daval, first author with Brigham and Women’s Hospital and Harvard University in Boston, stated in a press release.
Daval and his colleagues evaluated the number of advisory committees held between January 2010 and December 2021, the approval pathway for the drug, and the outcomes of any votes an advisory committee made, such as a positive or negative vote. The researchers included questions of overall approval as well as evidence of risk-benefit, whether the evidence supports approval, and if approval should be delayed.
“Because a negative vote presumptively indicates a lower degree of confidence among the panel of experts regarding a drug’s safety and efficacy, the decision to allow negative-vote products to market merits heightened scrutiny,” the authors said.
In total, 482 new drugs and biologics were identified, and 114 drugs (24%) were reviewed by an advisory committee prior to FDA approval. There was a decrease in the percentage of advisory committees held per year for drugs that were ultimately approved by FDA between 2011 (59%) and 2021 (6%). FDA approved drugs that received a negative vote from an advisory committee at a median of one per year, the researchers said. For drugs that received an advisory committee meeting prior to approval, an advisory committee voted positively for 104 drugs (91%) and negatively for 10 drugs (9%).
Among the drugs approved despite a negative advisory committee vote included roflumilast in 2011, florbetapir and omacetaxine mepesuccinate in 2012, olaparib in 2014, panobinostat and flibanserin in 2015, eteplirsen in 2016, selinexor in 2019, oliceridine in 2020, and aducanumab in 2021. (RELATED: FDA approves aducanumab for use in Alzheimer’s disease, Regulatory Focus 07 June 2021)
Concerning negative votes, the most common reasons provided by advisory committees in discussions were safety and efficacy (6 cases) and lack of evidence for a surrogate measure leading to clinical benefit (3 cases).
Why does FDA refer only some drugs to advisory committees?
The authors posed the question of whether “FDA has stable, transparent criteria for when it should refer a new drug to an advisory committee,” as the agency has provided “broad rationale” for lack of referral.
“The decade-long decrease in referrals of approved drugs to advisory committees suggests that the FDA needs specific criteria for how it chooses to subject new drugs to external scrutiny. Publishing referral criteria would improve accountability by allowing the public to compare the FDA’s referral decisions in individual cases against preexisting standards,” the researchers said.
The agency also does not typically elaborate on why it disagrees with an advisory committee negative vote when it approves a drug, they noted. The exception was after the controversial approval of aducanumab in 2021, which was approved over a nearly unanimous negative vote, where the Center for Drug Evaluation and Research at FDA justified the decision and addressed concerns raised by the advisory committee. (RELATED: FDA defends Aduhelm's accelerated approval, while others call for reform, Regulatory Focus 14 July 2021)
“The ‘response and rebuttal’ portion of aducanumab’s medical review offers a prototype for a transparent, meaningful, and consistent discussion over whether to allow a new drug to market,” Daval and colleagues said. “Robust engagement with the merits of a discordant recommendation, such as when an agency responds to public comment in the rulemaking process, would indicate that the FDA has responsibly considered the advice of the experts it convened.”
“Establishing procedures that make plain the reasoning behind these choices can better inform the public and bolster the credibility of FDA decision making,” they concluded. “It would also give the pharmaceutical industry clearer notice of when products will be subject to advisory committee review before approval and what questions will be asked of the advisory committee if it is convened.”
Health Affairs Daval et al.


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