Unwanted Advice? Frequency, Characteristics, And Outcomes Of Negative Advisory Committee Votes For FDA-Approved Drugs.

Abstract

Substantial controversy arose in 2021 when the Food and Drug Administration (FDA) approved the Alzheimer's disease drug aducanumab (Aduhelm) under its accelerated approval program despite a nearly unanimous negative advisory committee vote. Advisory committees are convened before some FDA decisions to provide insight for the agency's decision-making process. To understand the frequency, characteristics, and outcomes of cases in which the FDA authorizes a drug against the recommendations of an advisory committee, we reviewed all FDA advisory committee referrals for new drugs approved during the period 2010-21. The fraction of approved drugs that had been referred to an advisory committee decreased from 55percent to 6percent annually, with FDA approvals of negatively reviewed drugs occurring about once a year. Qualitative analysis of committee meetings revealed variability in the substance and wording of key voting questions. Reforms such as transparent criteria for when a drug should be subject to external scrutiny, consistent wording of voting questions, and clear regulatory responses to negative recommendations can better ensure public confidence in the FDA approval process.