Why does the FDA select certain drugs for adcomm meetings? Researchers want to know
Although their numbers have dwindled in recent years, FDA advisory committees have been in the spotlight, and some experts are now seeking reforms to make them more useful, including a trio of leaders from Harvard’s Program on Regulation, Therapeutics, and Law writing in the New England Journal of Medicine.
The perspective explains the way in which the FDA typically follows the guidance from its adcomm, although about once annually, it doesn’t, and those missed connections can lead to major blunders, as in the case of Biogen’s new Alzheimer’s drug aducanumab, which won approval via the accelerated pathway after no adcomm members voted in favor of its full approval, but then failed to obtain coverage from CMS, which requested additional randomized trials.
One of the PORTAL co-authors, Aaron Kesselheim, resigned from the adcomm that reviewed aducanumab, and this latest article hones in on an important and often non-transparent aspect of the adcomm process: that the FDA “has full discretion over not only whether to follow advisory committee recommendations but also whether to convene an advisory committee in the first place.”
Co-author Ameet Sarpatwari told Endpoints that two of the criteria that FDA might consider when decided when to schedule an adcomm “are the quality of the available evidence and the degree of harm from type I and II errors. Additionally, an emerging body of research has raised questions about cancer and orphan drug approval standards — these categories of approvals may also benefit from a default presumption that advisory committees will be held.”
Back in 2016, Linda Ann Sherman, former director of the FDA’s advisory committee oversight and management staff, explained how the decision to grant an adcomm is usually at the discretion of a division director, and those medical products that are selected are usually chosen because there’s a “new technology or some element of controversy.”
But Sarpatwari calls on FDA to issue guidance, “providing more clarity and consistency on when it will convene advisory committees for new drug approvals. As part of this process, it would be a good idea to solicit input from various stakeholders.”
Several of the recent meetings, particularly around Covid-19, have been highly controversial, including one recent one highlighted by the Harvard authors.
In this case, vaccine experts overwhelmingly voted against authorizing a booster shot for everyone 16 or older (16 to 2), so the FDA then sought a new vote on a question not included in the meeting’s agency on whether the FDA should just authorize a third dose for seniors and those at higher risk for severe Covid-19, which they voted unanimously in favor of, and the FDA authorized.
But several top FDA vaccine leaders resigned in the wake of a push for “boosters for all,” and the FDA later expanded eligibility to all adults and teens without turning to an adcomm.
The NEJM perspective also notes a major decline in the number of adcomms in recent years, as in 2010, more than 50% of newly approved drugs had received an adcomm meeting prior to their approval, but in 2021, the proportion had dropped to 6%.
A McKinsey report found that 37% of FDA-approved new chemical entities or new biological entities from 2001 to 2010 were subject to an adcomm meeting, so it’s unclear if those two years were outliers, as the pandemic has not only caused all adcomm meetings to move virtually, but has resulted in fewer meetings overall.
But Sarpatwari told Endpoints that these two years are not outliers and “but rather part of a steady decline,” noting two Health Affairs papers he co-authored in 2010 and 2021.
According to FDA’s adcomm calendar, CDER or CBER has held 21 adcomm meetings so far in 2022 (16 novel drug approvals, although not every adcomm was for a novel drug approval), compared with 26 meetings in 2021 (50 novel drug approvals), and 28 in 2020 (53 novel drug approvals).
Meanwhile, the Harvard authors in NEJM call on FDA to make three changes:
- Issue guidance explaining “how it decides whether to convene advisory committees, and it could commit to convening them for certain types of decisions (e.g., accelerated approvals).
- Publish in advance the questions it plans to ask (which the agency often does, although as in the case of the Covid-19 boosters, the questions can change on the fly), and it could “develop a standardized question structure for considering the approval or authorization of a medical product.”
- Publicly explain (via an established procedure) regulatory decisions that run contrary to adcomm recommendations.
“Even when the FDA has legitimate reasons for disagreeing with an advisory committee, it owes the public a thorough explanation of its reasoning. If the agency does not implement these practices itself, Congress can consider legislation requiring these changes,” Joseph Ross, Kesselheim, and Sarpatwari write.
Editor’s note: Article updated to include comment from co-author Ameet Sarpatwari of PORTAL.
