Robustness of ANCOVA in randomised trials with unequal randomisation

Abstract

Randomised trials with continuous outcomes are often analysed using ANCOVA, with adjustment for prognostic baseline covariates. In an article published recently, Wang \etal proved that in this setting the model based standard error estimator for the treamtent effect is consistent under outcome model misspecification, provided the probability of randomisation to each treatment is 1/2. In this article, we extend their results allowing for unequal randomisation. These demonstrate that the model based standard error is in general inconsistent when the randomisation probability differs from 1/2. In contrast, the sandwich standard error can provide asymptotically valid inferences under misspecification when randomisation probabilities are not equal, and is therefore recommended when randomisation is unequal.