Uses and limitations of randomization-based efficacy estimators

Abstract

In randomized trials with departures from allocated treatment, intention-to-treat analysis is important but not always sufficient. The most common supplement to intention-to-treat analysis is per-protocol analysis, whose assumption of comparability between different nonrandomized groups is often implausible. Randomization-based methods avoid making this assumption and are preferable. Situations where intention-to-treat analysis is insufficient and a randomization-based method is useful include provision of patient information, exploration of treatment-covariate and treatment-time interactions, meta-analysis, and equivalence trials.