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Aspiring to Reasonableness in Accelerated Approval: Anticipating and Avoiding the Next Aducanumab

Abstract

The US Food and Drug Administration’s decisions about drug approval—though guided by science, as well as relevant statutes, regulations, and guidance documents—reflect normative judgments about how the agency should exercise its discretion. This is particularly true in the context of the “accelerated approval” pathway, where the agency must balance speeding to market drugs for patients with unmet needs before they have been proven to work and ensuring confidence about the benefits and risks of those drugs. A key challenge in evaluating normative judgments such as these is that reasonable people can disagree, rendering it difficult to proclaim with certainty that a particular decision is right or wrong. Therefore, we propose that it is preferable to ask whether a decision is reasonable. A decision is reasonable when it transparently, comprehensively, and fairly balances the interests of affected parties, within the parameters of the decision maker’s legal authority. If a decision achieves these three qualities, it can be viewed as legitimate and worthy of trust and confidence, regardless of whether one agrees with the particular outcome. We recommend that the Food and Drug Administration adopt procedural protections to promote reasonableness in four domains affecting accelerated approval decisions: pathway gatekeeping, endpoint selection, stakeholder engagement, and deliberation. This should aid the agency in minimizing controversies, such as that surrounding the 2021 approval of aducanumab (Aduhelm; Biogen).

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Correspondence to Emily A. Largent.

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EL is supported by the National Institute on Aging (K01-AG064123) and the Greenwall Faculty Scholars Program. AP is funded by R21AG069805 and the Greenwall Faculty Scholars Program. JK is supported by the National Institute on Aging (P30-AG-072979). HFL is supported by the Greenwall Faculty Scholars Program. No funding was received specifically for the publication of this article.

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EL has no conflicts of interest or competing interests to report. AP has no conflicts of interest or competing interests to report. JK is a site investigator for clinical trials sponsored by Lilly and Biogen. HFL has no conflicts of interest or competing interests to report.

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EL, AP, JK, and HFL contributed to the formulation of the idea for the article; EL wrote the first draft of the article; and EL, AP, JK, and HFL critically revised the work. All authors read and approved the final submitted manuscript and agreed to be accountable for the work.

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Largent, E.A., Peterson, A., Karlawish, J. et al. Aspiring to Reasonableness in Accelerated Approval: Anticipating and Avoiding the Next Aducanumab. Drugs Aging 39, 389–400 (2022). https://doi.org/10.1007/s40266-022-00949-8

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