FDA’s adcomm process needs reform, researchers say

Regulatory NewsRegulatory News | 22 August 2022 | By

Reforms are needed to make the US Food and Drug Administration’s (FDA) advisory committee process more consistent and transparent, according to three researchers from the Program on Regulation, Therapeutics, and Law (PORTAL) at Brigham and Women’s Hospital and Harvard Medical School.
The researchers propose that FDA issue guidance spelling out how it decides whether to convene an advisory committee and committing to seeking advisory committee input for certain types of regulatory decisions, such as accelerated approvals. They also call on the agency to publish in advance the questions it will ask advisory committees to consider and to standardize some of the questions related to approval or authorization of products. Finally, the researchers ask FDA to commit to publicly explaining its reasoning when rejecting the advice of an advisory committee.
“Regulatory decisions lie with the agency, not its advisors,” C. Joseph Ross Daval and colleagues from PORTAL wrote in a perspective published in the New England Journal of Medicine. “But advisory committees cannot support public trust in FDA decisions if the agency uses them inconsistently. By committing to simple reforms, the FDA can better leverage expert recommendations to improve accountability, transparency, and trust.”
The FDA currently has 31 standing independent advisory committees and for drug and biologic agents, the agency has complete discretion over whether to convene the committees and whether to heed their advice. The researchers notedthat over the last decade the agency has relied on advisory committees less than before. In 2010, more than half of newly approved drugs were reviewed by advisory committees before approval, but that number fell to just 6% by 2021. (RELATED: FDA’s use of adcomms prior to drug approval decreased over the last decade, Regulatory Focus 03 May 2022)
When FDA does convene an advisory committee, it tends to agree with the committee’s recommendations. However, when the agency decides to approve a drug that an advisory committee has voted against, it can create controversy, such as with the FDA’s decision to grant accelerated approval to Biogen’s Alzheimer’s drug Aduhelm (aducanumab) in 2021, despite its Peripheral and Central Nervous System Drugs Advisory Committee voting against the drug’s approval.
The researchers also point to the controversy generated by FDA’s use of advisory committees in considering authorization of a third dose of the Pfizer-BioNTech COVID-19 vaccine. In September 2021, the Vaccines and Related Biological Products Advisory Committee voted against authorization of a third dose of the vaccine for all persons 16 years of age or older. The FDA then added a question not on the original agenda, asking the committee to consider a third dose for those 65 years of age and older and those at high risk for severe COVID-19, which was voted on favorably by the advisory committee. When the agency expanded eligibility for a third dose of the vaccine in November 2021 and again in December 2021, they did not convene the advisory committee.
“Of course, there were reasonable justifications for the FDA’s decision to authorize third doses the way it did,” the researchers wrote. “But the malleable role of advisory committees in these decisions contributed to a general lack of clear messaging about the utility of the vaccines and raised broader concerns about the basic purpose of FDA advisory committees.”
If FDA is unwilling to implement reforms to the advisory committee process on its own, Congress could consider legislating the changes, the researchers note. “Such reforms would not limit the FDA’s authority to seek expert advice or to ask any additional questions it deems appropriate, but rather set minimum requirements for certain decisions – a floor, not a ceiling,” they wrote.
Two of the authors reported grant support from Arnold Ventures. One author, Aaron Kesselheim, served as a member of the FDA Peripheral and Central Nervous System Drugs Advisory Committee from 2015-2021, until he resigned from the committee in protest over FDA’s decision to approve Aduhelm.
New England Journal of Medicine perspective


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