Covariate adjustment in randomized controlled trials with dichotomous outcomes increases statistical power and reduces sample size requirements

Abstract

Objective Randomized controlled trials (RCTs) with dichotomous outcomes may be analyzed with or without adjustment for baseline characteristics (covariates). We studied type I error, power, and potential reduction in sample size with several covariate adjustment strategies. Study Design and Setting Logistic regression analysis was applied to simulated data sets ( n = 360) with different treatment effects, covariate effects, outcome incidences, and covariate prevalences. Treatment effects were estimated with or without adjustment for a single dichotomous covariate. Strategies included always adjusting for the covariate (“prespecified”), or only when the covariate was predictive or imbalanced. Results We found that the type I error was generally at the nominal level. The power was highest with prespecified adjustment. The potential reduction in sample size was higher with stronger covariate effects (from 3 to 46%, at 50% outcome incidence and covariate prevalence) and independent of the treatment effect. At lower outcome incidences and/or covariate prevalences, the reduction was lower. Conclusion We conclude that adjustment for a predictive baseline characteristic may lead to a potentially important increase in power of analyses of treatment effect. Adjusted analysis should, hence, be considered more often for RCTs with dichotomous outcomes.