Contribute Try STAT+ Today

Last week’s controversial decision by the FDA to give aducanumab, Biogen’s Alzheimer’s drug, accelerated approval turned the spotlight on the role of FDA advisory committees.

News reports highlighted how the committee that advised the FDA on this drug, of which I was a member, voted against approving it. Since the decision, three members of the committee have resigned from it, one of whom recently called for “a new organization to review drug approvals.”

I have received several emails from colleagues, as well as questions from reporters, about whether I would serve again on an FDA advisory committee. My answer has been an unreserved and emphatic yes. I feel it is my duty as a clinician and a researcher to serve in this vital role, when and if I am asked to do it.

advertisement

Translating advances in science into improvements in human health rarely occurs in smooth, steady increments. Setbacks are just as common as eventual course corrections. The continued engagement of experts on panels like FDA advisory committees is far more likely to ensure that any miscarriages of science are remedied sooner than later.

In 2008, the FDA convened a meeting to discuss the utility of novel imaging methods that were then being developed to measure amyloid, the brain protein thought to be involved in Alzheimer’s dementia, to help diagnose people with the disease. As part of that group, I was tasked with presenting an overview of the disease to a diverse audience that included nonexperts and patient representatives.

advertisement

It was a momentous occasion because we were on the verge of making it possible for the first time for clinicians like myself to measure a characteristic pathological hallmark of Alzheimer’s in the brain using a noninvasive method. Before then, it had been possible only at autopsy by examining brain tissue under the microscope, using methods that had remained largely unchanged since physician Alois Alzheimer first described the disease that bears his name more than 100 years ago. It was exciting to see three pharmaceutical companies present preliminary findings from small studies using PET imaging of the brain.

Three years later, I served on another FDA advisory committee that evaluated data from Alzheimer’s patients near the end of their lives who had undergone brain PET scans and had consented to examination of their brains at death. This landmark study showed conclusively that the PET signal of amyloid in the brain was indeed a reliable marker of the telltale amyloid plaques in people with Alzheimer’s disease. The committee voted overwhelmingly in favor of approving this new radiochemical for PET imaging of brain amyloid.

Through my service on these two committees, I helped advance a paradigm-shifting innovation that has had far-reaching implications in patient care and research. Brain amyloid imaging is now an important addition to physicians’ diagnostic toolboxes and has dramatically transformed the ability to identify individuals at the earliest stages of Alzheimer’s disease. This means that present-day clinical trials testing drugs like aducanumab are far superior to those a decade ago because Alzheimer’s disease can be accurately identified early — a time when therapy is likely to have the greatest impact.

Even as the debate about the drug’s approval rages on, health care systems around the country are hurrying to make it available to millions of eligible Americans. As a physician who has cared for patients with dementia and conducted research on Alzheimer’s disease for nearly 20 years, I am seeing this happen in real time.

Two days after the approval of aducanumab (to be marketed under the brand name Aduhelm), I was in my clinic. I had just reviewed several neuropsychological test results, along with a brain MRI scan and results of blood tests, for a 78-year-old patient of mine. I compared the results of his recent cognitive performance to those from a year ago, and the conclusion was inescapable: He likely had Alzheimer’s disease. He sat motionless while his son made copious notes as I spoke, rarely taking his eyes off the notepad, his writing punctuated only by fleeting grimaces as I explained how I had arrived at the diagnosis, what we knew about the inevitable progression of the disease and the limited benefits of medications for symptomatic treatment of Alzheimer’s.

Then came the question — variations of which I have been asked several times since by patients and their loved ones — “When can my dad get the new antibody treatment?”

To prepare for this inevitable scenario, I had stayed up late the previous night, poring over the transcript of the advisory committee on aducanumab I had participated in last year. During the consultation with my patient and his son, I described the typical people who had been enrolled in both of Biogen’s Phase 3 trials of aducanumab: individuals in the early stages of Alzheimer’s with mild symptoms. I described how results from the two trials were at odds with each other. I then tried to explain how we had discussed and voted on questions related to the effectiveness of the drug.

I was especially keen to explain my own reasoning and why, like all but one of my 10 colleagues on the panel, I had been unconvinced that this drug was an effective Alzheimer’s treatment. I felt an overwhelming need to fully explain myself, to seek the patient’s validation of my judgment and for his son to agree with my assessment that I could not recommend the drug because his father’s disease was far more advanced than patients who had been enrolled in the clinical trials.

I do not know if my patient will follow my recommendation not to seek out this drug. We have agreed to resume the discussion in a few days.

While conversations about an Alzheimer’s diagnosis during a busy clinic are stressful at the best of times, they are further complicated by having to distill inconclusive clinical trial data and explain divergence between expert opinion and regulatory decisions. I am sure that this scenario is being played out in physician’s offices across the country.

As an Alzheimer’s disease researcher and clinician caring for people with dementia, I feel strongly that my patients — and all patients — are best served by science that is rigorously analyzed and interpreted through a transparent process that is open to all interested parties. FDA advisory committees fulfill an important role by convening experts who have no conflicts of interest and who have all accessed and analyzed the available data. Further, by providing all stakeholders — patients, patient advocates, scientific experts, pharmaceutical companies, and the public — unrestricted access to deliberations of these committees, including detailed transcripts of the proceedings and a platform to voice their concerns, they contribute to and enhance the quality of important public health debates.

By serving on FDA advisory committees when invited to do so, using my expertise to assess the quality of scientific evidence and by clearly articulating my opinions, I can be the best advocate for my patients.

Madhav Thambisetty is a neurologist in Ellicott City, Md., and an adjunct professor of neurology at Johns Hopkins University School of Medicine.

Create a display name to comment

This name will appear with your comment