Representativeness of Participants Eligible to Be Enrolled in Clinical Trials of Aducanumab for Alzheimer Disease Compared With Medicare Beneficiaries With Alzheimer Disease and Mild Cognitive Impairment

Abstract

In June 2021, the US Food and Drug Administration (FDA) granted accelerated approval for aducanumab to treat patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD), despite limited evidence of clinical benefit. The 2 phase 3 clinical trials of aducanumab, EMERGE and ENGAGE, were stopped prematurely based on prespecified futility thresholds. 1 Both trials also showed an increased risk of adverse events with aducanumab, including microhemorrhages and vasogenic brain edema, headache, and possibly falls. 1 Though both trials excluded patients based on age, certain chronic diseases, and use of antiplatelet agents and anticoagulants, FDA approval was granted without contraindications or precautions for these unstudied patient popula-tions. We evaluated whether patients enrolled in the trials of aducanumab were representative of patients with dementia enrolled in Medicare by estimating the proportions of Medicare beneficiaries with AD or MCI who would have been excluded from the trials.