Beyond advisory committees
How collaborative communities, patient advocacy groups and think tanks can help FDA receive the expert advice it needs
FDA has been most successful in fostering the development of safe, effective medicines when it has collaborated closely and transparently with patients, scientists and physicians to map out strategies for testing and evaluating medicines. Secrecy and isolation have led it into dark alleys, places where controversies like the accelerated approval of Aduhelm and the Emergency Use Authorization of hydroxychlorquine live.
Advisory committee meetings can serve as windows that shed light on FDA’s deliberations and as pathways for it to receive external advice and generate scientific and medical consensus. The advisory committee system, however, is broken.
FDA is reviewing the system, with results expected next year, but its ability to enact reforms will be limited by laws governing federal advisory committees and by the political attractiveness of portraying any attempt to modify conflict-of-interest rules as unlatching the henhouse door to make it easier for the fox to collect dinner.
The Center for Drugs and Radiological Health (CDRH) has embraced a model for obtaining external input and developing consensus on precompetitive issues that sidesteps these barriers that FDA’s drug and biologics centers should adopt.
Collaborative communities are self-organized forums that bring private- and public-sector members together to solve problems that individual entities or sectors can’t address alone. Rather than meeting sporadically like advisory committees, they meet often and evolve over time.
Collaborative communities can invite FDA to participate. Because FDA does not have control over how the communities operate and they do not provide formal advice to the agency, they are not subject to the Federal Advisory Committee Act.
The devices center has joined a dozen, so far, and created a toolkit to help foster the development of collaborative communities.
The Wound Care Collaborative Community, for example, works in the pre-competitive space to advance the creation of clinical evidence development tools and methods. It is undertaking a number of initiatives that could help FDA better regulate medical products, including providing advice on the kinds of clinical and preclinical evidence that are meaningful to patients, developing standards for evidence, and evaluating measurement tools that can be incorporated into clinical trials.
CDRH is also participating in collaborative communities involving ophthalmic imaging, standardizing laboratory practices for pharmacogenomics, liquid biopsies and heart valves.
FDA’s other medical product centers should learn from CDRH’s experience with collaborative communities and make it clear that they are open to participating in similar initiatives.
FDA’s centers for drugs and biologics have developed working relationships with a network of organizations that provide neutral ground for regulators, academics, patient advocates and product developers to collaborate to develop consensus on scientific, medical and policy issues.
Friends of Cancer Research, for example, has played major roles in achieving consensus on clinical trial design, surrogate endpoint, and other topics.
Think tanks, medical societies and patient advocacy groups have played important roles in providing external advice and creating consensus in ways that are less adversarial and more thoughtful than the outcomes of advisory committees.
In contrast to advisory committees, which typically meet to discuss specific product applications and therefore intervene late in the product development cycle, groups that provide neutral ground for regulators and other stakeholders can smooth the path for product development, making approval decisions less contentious and more predictable.
FDA made deft use of external advice and consensus-building bodies to pave the way for a pioneering sickle cell disease therapy.
In 2018, FDA and the American Society of Hematology (ASH) co-hosted a Sickle Cell Disease Clinical Endpoints Workshop and FDA held a patient focused drug development meeting that discussed sickle cell endpoints, including increases in hemoglobin expression.
In 2019, when Global Blood Therapeutics Inc. (NASDAQ:GBT) submitted an NDA for Oxbryta voxelotor to treat sickle cell disease, FDA did not find it necessary to hold an advisory committee meeting, even though the company sought accelerated approval based on increases in hemoglobin expression, an endpoint that had never previously been used to support approval.
Organizations such as the Duke-Margolis Center for Health Policy, Friends of Cancer Research, the congressionally chartered Reagan-Udall Foundation for the FDA, Critical Path Institute, and the Massachusetts Institute of Technology’s NEW Drug Development ParadIGmS (NEWDIGS) consortium have played valuable roles in providing FDA external expertise and bringing stakeholders together to agree on standards and policies.
The Centers of Excellence in Regulatory Science and Innovation (CERSIs), a collection of collaborations between FDA and academic institutions to advance regulatory science, are an under-utilized resource.
FDA could expand its interactions with and, where necessary, funding of these groups.
First, it should develop and publicize policies to assure the public that these groups aren’t making regulatory decisions, providing advice on specific product applications, or serving as fronts for industry or interest groups.
FDA should also promulgate guidelines ensuring that, whenever possible, the meetings its officials participate in are public, and when they are private that information about the meetings is made public in a timely manner.
With guardrails are in place, FDA’s medical product centers should develop plans to expand its work with collaborative communities, patient advocacy and academic groups and think tanks. The agency’s decisions are rooted in science, and science is best pursued in public and with the broadest possible participation.