Post by icemandios on Jul 8, 2023 1:54:49 GMT
July 7, 2023 12:03 PM EDT
FDA+
No more FDA adcomm votes? Reforms brew as new research highlights decline in meetings
Zachary Brennan
Senior Editor
As the FDA explores how to reform its advisory committees in ways to ensure the agency receives more timely and sound advice — a process the agency acknowledges is ongoing and not easy — new research points to a decline in adcomms in recent years, and an FDA commissioner who has insisted there may be fewer votes at future meetings, too.
From 2010 to 2021, the FDA held 409 adcomms related to human drugs, but the meetings were convened “less frequently over time, from a high of 50 in 2012 to a low of 18 in 2020 and 2021,” researchers from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) wrote in JAMA Health Forum today. “Much of this decrease occurred at committee meetings involving votes on initial approvals, which declined from a high of 26 in 2012 to a low of 8 in 2021.”
Adcomms in general have become slightly less controversial than the fever pitch of critiques the agency faced after several members of the adcomm that voted unanimously against Biogen’s Alzheimer’s drug Aduhelm (aducanumab) resigned in protest of its accelerated approval.
The adcomm that recently reviewed Aduhelm’s successor, Leqembi, which won a full approval yesterday, sailed through with a unanimous vote, but with just six voting members on the committee, and not without controversy.
The FDA had sought but then reversed course at the last minute on adding David Weisman, a neurologist with Pennsylvania-based Abington Neurological Associates who worked on clinical trials for Eisai and Biogen, for the Leqembi (lecanemab) adcomm meeting. Weisman had received tens of thousands of dollars from Eisai and partner Biogen over the last five years, and been vocal about his support for lecanemab, making his impartiality a question mark.
“The fact that FDA and Dr. Weisman apparently consider this a ‘potential’ conflict of interest, rather than an obviously outrageous conflict of interest, tells us that FDA needs to hire some bioethicists to help them vet Advisory Committee members,” Diana Zuckerman, president of the National Center for Health Research, said via email.
But dismissing industry favoritism with its adcomm process may be a tall task for FDA as so far this year, 18 of 19 drug-related adcomms have ended with a positive result for industry.
FDA Commissioner Rob Califf has spent much of this year also discussing reforms that are ongoing and may include fewer voting questions in some cases, saying that the discussion sections of the meetings are the important points that the agency relies on to help make its approval decisions.
The FDA in a statement to Endpoints News similarly made clear that votes are “not a mandatory part” of the adcomm process, adding that adcomm “members’ rationale for their vote is most valuable to the FDA.”
But even some FDA insiders like Rick Pazdur have made clear that they think voting is crucial. “I think we need to vote,” Pazdur said at ASCO, according to STAT News. “We have to make a binary decision at FDA whether to or not to approve. If we are going in one direction, and we hear a unanimous vote against — we have to pause. You have to step back and say, were we wrong on this?”
Others outside the agency have pointed to the need for adcomm votes too, if nothing more than as a quick way to shore up outside question marks.
“The up or down votes provide clear recommendations that the public can interpret, and when FDA’s actions align with the recommendations it can support credibility and trust (E.g. ‘a panel of independent experts agreed that this vaccine is safe for your child’),” first author Joseph Daval of PORTAL told Endpoints. “When they don’t align, it’s better that the public knows that a panel of experts disagreed, as with aducanumab. So basically, voting is a win-win.”
Sidney Wolfe, co-founder and director of Public Citizen’s Health Research Group, told Endpoints that the devolution of adcomms has gotten worse over time, and he doesn’t expect much from any reforms as they are part of “the rapidly growing number of ‘Califf-isms’ that threaten the independence of the FDA.”
“Of the 15 FDA commissioners since I left NIH to start this group, Califf is the worst by far,” Wolfe, a vocal critic of FDA for decades, added in a voicemail.
Where does industry stand on adcomm votes? A PhRMA spokesperson declined to discuss any potential reforms around voting questions (since no PhRMA member companies are ever voting members of any adcomm), but added in a statement,
While advisory committee recommendations do not and should not determine the outcome of regulatory decisions, the biopharmaceutical industry believes that advisory committee members, including the non-voting industry representatives assigned to each advisory committee, are an important part of the rigorous human drug review process we have in the United States.