FDA's advisory committee process is one of the agency's greatest institutional strengths. No other major drug regulator conducts scientific advisory meetings as publicly -- or as visibly -- as FDA. Scientific disagreements are debated in full public view, under the scrutiny of patients, physicians, companies, investors, reporters and regulators from around the world.
Every question, every disagreement and every vote become part of the public record. That transparency is one of FDA's greatest strengths, and one reason FDA advisory committees command such extraordinary attention. It is also why getting them right matters.
The previous FDA leadership often treated advisory committees as optional. If a meeting advanced certain agendas, it went forward. If it threatened to complicate them, it could disappear. That approach weakened confidence in the advisory committee process and, by extension, confidence in the agency itself. Rightfully so.
Restoring the integrity of advisory committees is an important first step, but simply returning to the old model isn't enough. Advisory committees shouldn't exist to rubber-stamp decisions FDA already wants to make, nor should they serve as political theater. Their purpose is to challenge FDA's thinking, expose competing scientific interpretations and improve regulatory decision-making. Regulatory science advances through rigorous debate, not manufactured consensus.
The recent Capricor advisory committee illustrates why reform is needed. Deramiocel, a proposed treatment for cardiomyopathy associated with Duchenne muscular dystrophy, raised exceptionally difficult scientific questions involving small patient populations, imperfect endpoints, natural-history controls and substantial unmet medical need. FDA has confronted many of the same issues while evaluating therapies for ALS. These are not routine product reviews. They are precisely the kinds of cases for which temporary voting members were created.
FDA already has the authority to appoint temporary voting members whose expertise matches the application under review. It should use that authority much more aggressively. Standing committees provide continuity and institutional memory, but continuity is an administrative virtue, not a scientific qualification. No standing committee can reasonably include the nation's foremost experts in every rare disease, every emerging technology and every evolving clinical endpoint. Temporary voting members are FDA's opportunity to close that gap.
When FDA reviews a Duchenne therapy, it should recruit physicians who care for Duchenne patients every day, pediatric cardiologists who understand the disease's unique cardiac progression, investigators who have designed Duchenne clinical trials and scientists who have developed the field's natural-history databases. When reviewing an ALS therapy, the committee should include neurologists specializing in motor neuron disease, experienced ALS clinical investigators and experts in biomarkers and disease progression. The objective should not be to assemble the most available committee. It should be to assemble the right committee.
Doing so isn't easy. The nation's leading specialists are busy. Many have conducted industry-sponsored research, advised biotechnology companies or served on independent data monitoring committees. Identifying the right people, evaluating potential conflicts intelligently and persuading them to serve takes real work. FDA should make that investment anyway.
The work of building a great advisory committee begins months before the meeting opens. By the time the briefing documents become public, FDA has already made one of its most important scientific decisions -- who will be sitting around the table. Recruiting temporary voting members is not an administrative afterthought. It is one of the most important scientific decisions FDA makes. Get that decision wrong, and the rest of the meeting becomes an uphill climb. Predictable committees produce predictable advice. Exceptional committees ask better questions, identify weaknesses others miss and often change the way FDA thinks about difficult scientific problems. That is exactly what advisory committees are supposed to do.
This is not a criticism of the Capricor committee or its members. They brought impressive expertise in statistics, epidemiology, cardiology, neurology and radiology. Those disciplines belong at the table. The point is different. For highly specialized diseases, they should be joined by the nation's foremost disease experts serving as temporary voting members.
The Capricor discussion focused on statistical analyses, endpoint interpretation and even the wording of the final voting question. The committee concluded that the evidence did not constitute substantial evidence of effectiveness, but the vote itself revealed relatively little about the committee's reasoning. Did members question the biological effect, the clinical endpoints, the statistical methodology or simply conclude that the legal standard had not been satisfied? Different members may well have reached the same conclusion for entirely different reasons.
FDA should ask advisory committees to answer those questions directly. Members should vote on whether endpoints are clinically meaningful, whether imaging measures are reliable, whether statistical analyses are persuasive, and which patients appear most likely to benefit. Those answers would provide FDA, physicians, patients and investors with far more useful guidance than a single yes-or-no vote on approvability.
FDA should also continue refining its approach to conflicts of interest. Individuals with direct financial interests should not vote. At the same time, FDA should not unnecessarily exclude the country's leading specialists simply because they have participated in legitimate clinical research or advised companies developing therapies. In rare diseases such as Duchenne muscular dystrophy and ALS, expertise is scarce. Treating experience as a liability often excludes precisely the people FDA most needs to hear from.
The lesson extends well beyond one meeting. Standing committees should provide continuity. Temporary voting members should provide specialized expertise. Advisory committees exist to improve FDA's decisions, not merely affirm them.
The hardest scientific questions deserve the best scientific minds. FDA should settle for nothing less when it builds its advisory committees.
Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest. Robert Goldberg is Vice President of Research Programs at the Center for Medicine in the Public Interest.
