Allowing “rescue therapy” in preclinical Alzheimer’s trials

Aduhelm’s recent approval, and the potential approval of additional effective therapies in early (prodromal‐to‐mild) Alzheimer’s disease (AD), will impact the conduct of clinical trials, including trials designed to delay or prevent cognitively unimpaired participants from progressing to mild cognitive impairment (MCI) or AD dementia. Allowing “rescue therapy” with these approved therapies during preclinical AD trials (“treatment policy design”) is expected to increase participation and improve adherence in these very large and long clinical trials. Our goal was to evaluate the impact of allowing “rescue therapy” on the study power using simulation.