There is a tempest brewing at the Food and Drug Administration (FDA). Recently, the agency opted to approve aducanumab, which is the first drug on the market potentially capable of slowing down Alzheimer’s disease. The medication was approved amid considerable controversy with many detractors of the purported wonder drug. And now, three medical experts on the FDA’s advisory committee have resigned in protest.
But the flare-up over aducanumab shows not some flaw with FDA decision-making, but rather deeper issues with the agency’s overly broad mandate. The FDA should address these resignations by clarifying their mission and ensuring that vacancies don’t hobble the agency’s core functions. There’s no turning back now from a wiser, more flexible FDA that puts the needs of patients first.
Big decisions carry large consequences. In evaluating aducanumab, the FDA faced a number of trade-offs. It was clear from most observers examining the research that the medication, which supposedly slows down the progression of Alzheimer’s, is not a sure thing. While one major trial affirmed the efficacy of the drug, another analysis concluded that the drug did not work as intended. Safety wasn’t an issue with this drug because there was agreement that side-effects were well-managed over the course of the drug’s administration. And overall, rates of adverse events appear to be similar between the placebo given during the trials and high doses of the medication.
The question therefore boiled down to whether the FDA should approve a largely safe drug that may well slow the progression of a devastating disease with a 100 percent fatality rate. The FDA wisely opted to err on the side of hope, but members of the agency’s “Peripheral and Central Nervous System Drugs Advisory Committee” were none too pleased. All but one of the committee’s 11 members voted against green-lighting the medication (with the final member voting “uncertain”). Harvard Medical School professor Dr. Aaron Kesselheim penned a sharply worded resignation letter following the FDA’s approval of aducanumab, calling the agency’s verdict, “probably the worst drug approval decision in recent U.S. history.”
In his letter, Dr. Kesselheim raises some interesting concerns not directly related to the scientific nitty-gritty of the decision. The medical expert fears that, should the FDA continue to green-light drugs that may wind up not working, public trust in the agency may erode while the healthcare system becomes even more expensive. The fragile nature of the FDA’s public trust, though, runs far deeper than any one agency approval decision. Congress requires the agency to attest to not only the safety of medications, but also the effectiveness of drugs prior to approving them. It is therefore difficult to trust the agency if the FDA gives the seal of approval to a medication and then the drug turns out not to work.
The agency could approve promising, less-than-proven drugs without fear of a credibility crisis, but only if the Congressional mandate is relaxed. If lawmakers and the agency were clear that some approved medications might not pan out, patients could know what they were getting into before trying out a cure for an “incurable” illness. This in turn would allow advisory committee members to get a clearer picture of what they are signing up for and permit a wider scope of disagreement among experts.
Size also matters when it comes to advisory committees. Even though the FDA can disregard the results of committee votes, the agency is understandably reluctant to create a mass walk-out. Larger, more inclusive advisory committees can solve this issue while bringing more voices to the table. Integrating more economists into the decision-making process could lead to a more robust consideration of opportunity costs and the long-term healthcare financing consequences of an approval decision. In its 2019 report, the Taxpayers Protection Alliance issued additional recommendations for FDA advisory committees, including tightening vacancy standards and being more proactive in identifying conflicts of interest.
The notoriously risk-averse FDA is moving in a positive direction. For the first time ever, Alzheimer’s patients have hope that they’ll be able to cling onto their memories even for just a bit longer.
The FDA and Congress must work together to ensure that other promising drugs are available to the patients that need them the most.
This article was originally posted on FDA advisor exits show need for reform