FDA decisions based on limited evidence cause ethical dilemmas for physicians

Key takeaways:

• Certain decisions by the FDA can put patients at risk while impeding scientific progress and causing ethical dilemmas for physicians.
• Ethics consultations and group discussions can help address moral distress.

SAN DIEGO — The FDA faces substantial pressure from patients and their families that can lead it to make questionable decisions, causing moral distress among physicians, according to a speaker at the ACP Internal Medicine Meeting.

During his presentation, Kenneth Prager, MD, FACP, a professor of clinical medicine at Columbia University Medical Center, gave the example of the approval of Aduhelm (aducanumab, Biogen/Eisai) for Alzheimer’s disease.

The FDA approved aducanumab as the first disease-modifying therapy for Alzheimer’s disease in June 2021, despite a recommendation from its advisory committee to reject approval because of insufficient evidence that the drug slowed cognitive decline.

The FDA, under significant pressure, justified the approval “because the families of Alzheimer’s patients made it clear that they are willing to accept the trade-off of some uncertainty about clinical benefit in exchange for earlier access to a potentially effective drug,” Prager said. There was also substantial pressure from the Alzheimer’s Association to approve aducanumab, he added.

“Here you have a societal issue that is being influenced by the very same thing you and I are influenced by when we’re sitting in our office facing a patient and family one-on-one,” Prager said.

The case of aducanumab was just one of nearly two dozen recent instances of the FDA proceeding with drug approval despite inconclusive results. From 2018 to 2021, of the 210 drugs approved by the FDA, 21 had null findings for one or more primary end points, Prager pointed out.

He explained that approving drugs for which evidence has not been established can:

• “derail scientific progress”;
• expose patients to potential risks that outweigh benefits; and
• “allow hope to be exploited for commercial benefit ... with high costs to the health care system.”

Prager added that the FDA “has obligations to future patients, and future patients are more likely to favor more rigorous evidence of efficacy and safety.”

Ultimately, on the physician level, the approval of drugs with insufficient evidence of their efficacy or safety leaves physicians wondering whether it is right to prescribe them, Prager said.

“Ethics consultation and peer group discussion can alleviate such distress,” he said. “It’s not always right or it’s always wrong. I think that each decision has to be made in the context of the clinical circumstances that relate to that unique patient. For the FDA, obviously, it’s a different story.”