The Food and Drug Administration (FDA) is failing patients with life-threatening rare diseases.
As a biochemist and public health expert, I have witnessed officials turning a blind eye to the needs, concerns, and voices of families caring for the nearly 30 million Americans — half of them children — with debilitating and terminal rare conditions.
These patients and families have a simple, reasonable demand of the FDA — access to new treatments that offer the hope of longer and more productive lives. But rather than clearing the path, the FDA keeps blocking the gate with cumbersome bureaucracy.
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Many critical decisions affecting whether treatments reach patients in a timely manner are influenced by FDA Advisory Committees, or “AdComms.” These panels are comprised of experts from outside FDA who evaluate the safety and efficacy of new therapies, particularly those involving emerging technologies.
The AdComms carry enormous influence. Their conclusions shape regulatory decisions and can determine whether patients gain access to potentially life-saving treatments.
For families battling rare and often fatal diseases, these decisions are a matter of life and death. Patients are dying while committees debate. That is why the entire AdComm structure requires urgent reform.
The FDA’s review process is often criticized as influenced by special interests and even ideological bias, meaning trial designs and regulatory decisions can be subjected to pressures with little to do with treating rare disease patients for whom the biggest “risk” is doing nothing.
A lack of AdComm procedural transparency creates a web of detrimental consequences for patients placing trust in a system that is supposed to serve them. When life-saving treatment decisions are influenced by opaque processes that cannot demonstrate genuine independence, confidence in the entire system erodes.
So who are these people tasked with such lifesaving decisions?
Committee members are selected for broad expertise in drug development, statistics or safety rather than deep knowledge of the specific rare diseases and associated treatments being evaluated, which means advisory committee members are not necessarily experts in the diseases under review.
That approach can work for treatments for common conditions with reasonable demand for longer-term evaluation. It is far less appropriate for gene therapies or other treatments for rare disorders, where disease-specific expertise is essential, and timetables are as short as many patients’ lifespans.
Advisory committees do not always appear to operate with the level of independence patients deserve. Members can feel pressured to move towards a consensus position rather than making the choices that they are led to by science and patient input.
That should concern anyone who believes these committees exist to provide rigorous, independent scientific scrutiny.
The public nature of AdComm hearings can turn them into media spectacles. While transparency is valuable, some hearings lead to grandstanding and become advocacy campaigns rather than careful scientific inquiries. This is not performance art; this is life and death.
One study also showed that some AdComm members have financial ties to drug sponsors and other conflicts of interest, potentially influencing the public record presented to committee members.
Perhaps most critically, many AdComms remain wedded to clinical trial standards that do not reflect the realities of rare disease drug development.
For patients with rare conditions, traditional placebo-controlled trials are often impractical, if not impossible — and in some cases, arguably unethical. The FDA has expanded its acceptance of natural history studies, biomarkers, and other forms of real-world evidence. Yet AdComms do not always seem to evolve at the same pace.
As former FDA Associate Commissioner Peter Pitts recently observed, the evidentiary model embedded in U.S. drug regulation was “built for a different era” and relies on patient populations large enough to support traditional clinical trials – populations which often do not exist when dealing with rare diseases.
This disconnect has real consequences for patients and families who cannot wait for a perfect dataset that may be unattainable. When evaluating rare disease therapies, the question is not whether evidence resembles a common-condition drug trial, but whether the totality of the evidence supports giving patients a meaningful chance.
Reform is urgently needed. AdComms should include experts who understand the urgency of treatment for rare diseases under review and the new world of biologics. They need greater transparency and independence, insulated from pressures that have little to do with science.
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We live in a time of true medical miracles — inconceivable even a decade ago — brought to us by brilliant, dedicated scientists. The FDA must remove barriers between that progress and rare disease patients whose lives hang in the balance.
An evaluation and restructuring of AdComms is a good place to start.
Trica Flanagan is a bioscientist specializing in immuno-oncology, with some of her work now incorporated into NIH protocols. She is the founder and CEO of Azuza Laboratories.