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FDA is looking for greater consistency and fewer surprises in discussions by and decisions from its cadre of expert, independent advisory committees. These panels are formed to provide scientific and medical expertise to help shape FDA decisions in all regulatory areas, most notably to evaluate, approve or reject applications for new drugs, biologics and medical products. To gain a more efficient and transparent advisory system, the Center for Drug Evaluation and Research (CDER) has launched an initiative to gain more efficient and transparent operations of its advisory panels, says CDER director Patrizia Cavazzoni.
The initiative has gained attention in the wake of the recent loud eruption over FDA’s approval of Biogen’s Alzheimer’s drug June 7, 2021, despite strong opposition from an advisory committee at a meeting in November 2020. Although Cavazzoni’s comments on the role of advisory committees aired a week later (June 14, 2021) at the annual meeting of the Biotechnology Innovation Organization (BIO), the virtual presentation was recorded in late May, before the controversial Aducanumab approval decision. Three members of the Peripheral & Nervous System Drugs advisory committee publicly resigned in protest, criticizing FDA for ignoring the independent, scientific recommendations of the panel.
At the BIO meeting, Cavazzoni said that FDA is taking a “comprehensive look” at its advisory committee program to ensure appropriate expertise on its panels, with an eye to reducing some of the “emotional undertone” that may come from some members and public stakeholders. She called for FDA to partner with industry to examine the structure, purpose and operations of advisory committees, a topic that BIO also is reviewing to provide input. Cavazzoni noted that it is important to “get back to the fundamental reasons for advisory committees” and for all participants to listen to “thoughtful responses to questions from experts.” Most important is to limit some of the emotional comments from members, including reactions to some public speakers. “We have seen,” she said, “how a committee can be swayed by emotion in the face of very hard facts.”
Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), also commented at the BIO meeting that FDA has tried to follow the science throughout the pandemic and emphasized that approach regularly with the advisory committee process. But it’s “challenging,” he observed, to bring together a group of advisors that doesn’t normally sit together and to have them come to a strong conclusion, despite variables raised by non-scientific issues.
Cavazzoni explained that FDA has to contend with visible constraints in assembling advisory panels due to strong conflict-of-interest (COI) rules that keep many experts out of the committee- member pool. The result, she pointed out, is that some panels lack prominent experts in a field. FDA’s COI waiver process can help deal with this limitation, but Cavazzoni said that it doesn’t fully address the problem.
FDA has long relied on expert advisory committees to address the often controversial and subjective issues raised by the clinical assessment of new medicines, particularly in cases where an application is based on early evidence of potential patient improvement, but not clear long-term results. Among its highly controversial decisions is FDA’s approval in 2016 of etepliresen to treat Duchenne muscular dystrophy, despite opposition from its advisory committee, but with intense support from patient representatives.
Consumer advocates and other stakeholders have criticized FDA advisory committees for including too many experts with industry ties and for doing too little to identify qualified public and consumer representatives for its panels. Congress enacted legislation in 2007 requiring FDA to conduct more outreach to identify non-industry experts for the committees and to file annual reports annually on advisory panel vacancies, agency outreach efforts to identify suitable members, and the frequency of COI waivers on these panels. The agency’s annual report for 2019 on this program found a decrease in the use of waivers, and that of some 333 applications to serve on advisory panels, 40% were qualified and willing to serve.1 Yet FDA sees a continued need to authorize COI waivers because many individuals who have financial relationships with regulated industry also have expertise that is important to a discussion. Similarly, the agency often finds it difficult to identify alternative experts without any financial interests.
Any revisions in advisory committee practices are likely to acknowledge the efficiencies gained from virtual sessions, as has been the case for most FDA staff meetings and interactions with sponsors and other stakeholders during the pandemic. Remote meetings may continue even as FDA moves to a “new normal,” Cavazzoni said. Marks noted that some sponsors really like to come in to interact with reviewers, but remote meetings free up more time for them, and also for FDA. Virtual meetings are easier to schedule and impose less of a time and cost burden on committee members, and Cavazzoni envisions a more “hybrid model” with not all meetings in person, but not all remote [see https://www.fda.gov/advisory-committees for more information].