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Challenges to approval decisions have prompted FDA officials to reexamine of the role and composition of the agency’s many advisory committees and to explore options for change.
Recent challenges to certain controversial approval decisions have prompted FDA officials to reexamine of the role and composition of the agency’s many advisory committees and to explore options for change. With more than 50 panels composed of academics, scientists, and various interested parties, the program has become overly complex and sometimes contentious, with some up-or-down votes on important approval decisions appearing at odds with ultimate decisions by agency reviewers.
Commissioner Robert Califf has been calling for changes to improve the operations and composition of its advisory panels for several months. In a keynote speech on May 17, 2023, at the annual meeting of the Food and Drug Law Institute (FDLI) in Washington, D.C., Califf emphasized the need for the agency to strengthen committee structure and methods to be “more efficient, flexible, and effective in the exercise of our regulatory responsibilities".He noted the value of interchange among FDA experts and those outside the agency, particularly on complex scientific issues, and that transparent discussion is important. But he also said that the advisory committee system “can be improved” to enable FDA scientists to “get the best advice possible.”
Similarly, Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research (CDER), cited plans at the FDLI meeting for advisory committee “modernization” among numerous key initiatives for her office in the coming months. The process will include efforts to refine the selection of advisors so that their “expertise applies precisely to the matters under consideration.” That may involve adding to advisory panels more temporary members with special knowledge about the drug or disease under discussion and taking steps to ensure diversity in geographic areas represented.
Cavazzoni also noted the need for FDA to improve how it communicates about advisory committee operations and their relationship to the agency. This involves emphasizing to the public that these panels play an advisory role to the agency—and that FDA retains ultimate decision-making authority.
FDA’s interest in updating advisory committee composition and operations has become more visible in recent months, stemming from the uproar that resulted when FDA granted accelerated approval in 2021 to Biogen’s Alzheimer’s treatment, Aducanumab, despite a near-unanimous vote against approval at an advisory meeting in November 2020. Three panel members resigned in protest, and Medicare limited coverage to those patients participating in ongoing clinical trials.
That controversy, and subsequent heated debates over the approval of other treatments for critical diseases with questionable efficacy data, has prompted FDA officials to reconsider the advisory committee process, including the composition of the panels and the issues identified for discussion. A main change would be to shift away from “gladiator votes”—yes-or-no decisions on specific applications—and to provide more nuanced opinions on the main issues. But in some cases, the absence of up-or-down votes on key questions may generate confusion as to what the committee experts actually recommend. In the recent consideration of Sarepta’s new gene therapy to treat Duchenne’s muscular dystrophy, the advisory committee supported approval by a very slim margin. However, the patient advocate on the panel made a strong case for FDA to approve the drug as another treatment option for this devastating condition. FDA staff has gone back to the drawing boards, indicating it may limit treatment to a very young age group pending further clinical results.
Interchange among outside experts on scientific and technologic questions is important, Califf emphasized at the FDLI meeting. Such debate “makes our decisions better,” he noted, and “adds a level of transparency.” However, the commissioner also raised concerns about the steady stream of “misinformation and disinformation” in society that can undermine public confidence in science and “weaken faith in governmental and other institutions, including the FDA.”
Public debate among expert advisors can both support sometimes controversial decisions by FDA staffers, but also raise challenges to agency actions. The advisory committee process is one element in this ongoing debate that appears open to improvement, and Califf advised the regulatory community to “stay tuned for developments in this area.”
Jill Wechsler is Washington reporter for Pharmaceutical Technology.