A Simulation-Based Comparison of Covariate Adjustment Methods for the Analysis of Randomized Controlled Trials

Covariate adjustment methods are frequently used when baseline covariate information is available for randomized controlled trials. Using a simulation study, we compared the analysis of covariance (ANCOVA) with three nonparametric covariate adjustment methods with respect to point and interval estimation for the difference between means. The three alternative methods were based on important members of the generalized empirical likelihood (GEL) family, specifically on the empirical likelihood (EL) method, the exponential tilting (ET) method, and the continuous updated estimator (CUE) method. Two criteria were considered for the comparison of the four statistical methods: the root mean squared error and the empirical coverage of the nominal 95% confidence intervals for the difference between means. Based on the results of the simulation study, for sensitivity analysis purposes, we recommend the use of ANCOVA (with robust standard errors when heteroscedasticity is present) together with the CUE-based covariate adjustment method.