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    FDA Accelerated Drug Approval

    Bioethicists and MEHP Online faculty Ezekiel J. Emanuel, Emily Largent, and Holly Fernandez Lynch have been active participants in an ongoing discussion of how to improve the US Food and Drug Administration (FDA)’s accelerated drug approval process. Following the controversy surrounding accelerated approval of Biogen’s aducanumab (Aduhelm) treatment for patients with Alzheimer’s disease, they have proposed overlapping frameworks to improve accountability for drug companies. Their frameworks are also meant to improve trust in the FDA’s decisions.

    In a 2021 JAMA viewpoint, Dr. Emanuel suggests 4 potential policy changes based on the aducanumab approval experience:

    • Assuring that surrogate or intermediate endpoints for drug trials are highly or moderately correlated with long-term clinical benefit.
    • Requiring a commitment in advance from drug companies seeking accelerated approval regarding conducting a confirmatory trial.
    • Requiring transparency in recruitment, progress, and deadlines for completion of confirmatory trials.
    • Requiring that indication for the drug be the same in preliminary and confirmatory trials, unless there is good scientific reason to do otherwise.

    In a 2022 article in Drugs & Aging, Fernandez Lynch and Largent—with their collaborators Andrew Peterson and Jason Karlawish—look to establish criteria for accelerated approval that would “assure that even those who disagree with the FDA’s decisions can nonetheless recognize them as legitimate.”

    These include:

    • Pathway gatekeeping: requiring drug companies to commit to key steps including timely application for accelerated approval and commitment to deadlines for confirmatory trials.
    • Endpoint reasonableness: selecting endpoints for drug trials that have strong evidentiary support.
    • Stakeholder engagement reasonableness: engaging not just patients, but also caregivers, clinical experts, and other members of society that stand to be impacted when attempting to gain insights into the risks and benefits of a new treatment.
    • Deliberative reasonableness: cultivating an ethos of neutrality in making approval decisions by committing to consider the strongest arguments both for and against approval.

    Finally, in a 2022 research article in Health Affairs, Emanuel, with colleagues Richard G. Frank and Mahnum Shahzad, brings evidence to the question of how to encourage drug companies to complete timely confirmatory trials. Sampling physician-administered cancer drugs, they find that there is no relationship between the completion of confirmatory trials and pricing for the drugs. This “represents a failure of the market to reward reduced uncertainty,” they conclude, that could be “mitigated if major payers such as Medicare built price schedules that directly rewarded completion of confirmatory trials.”

    Learn more about MEHP Online faculty’s engagement with the FDA’s accelerated drug approval process by reading:

    • Emanuel, Ezekiel J. “A Middle Ground for Accelerated Drug Approval—Lessons from Aducanumab.” JAMA 326, no. 14 (October 12, 2021): 1367–68. https://doi.org/10.1001/jama.2021.14861.
    • Frank, Richard G., Mahnum Shahzad, and Ezekiel J. Emanuel. “Accelerated Approval of Cancer Drugs: No Economic Reward for Drug Makers That Conduct Confirmatory Trials.” Health Affairs 41, no. 9 (September 2022): 1273–80. https://doi.org/10.1377/hlthaff.2022.00119.
    • Largent, Emily A., Andrew Peterson, Jason Karlawish, and Holly Fernandez Lynch. “Aspiring to Reasonableness in Accelerated Approval: Anticipating and Avoiding the Next Aducanumab.” Drugs & Aging 39, no. 6 (June 1, 2022): 389–400. https://doi.org/10.1007/s40266-022-00949-8.