Covariate Adjustment in Randomized Experiments with Incomplete Baseline Data

When analyzing data from randomized clinical trials, covariate adjustment can be used to account for chance imbalance in baseline characteristics and to increase precision of the treatment effect estimate. A practical barrier to covariate adjustment is the presence of missing data in covariates, which raise various questions in implementation. In this paper we review several covariate adjustment methods with incomplete data, including complete data analysis and imputation-based methods, and investigate the implications of the missing data mechanism on estimating the average treatment effect in randomized clinical trials with continuous or binary outcomes. We consider both the outcome regression and propensity score weighting adjustment methods. We conduct comprehensive simulation studies to compare these methods. We find that performing adjustment with imputed covariates, regardless of adjustment method or imputation method, generally improves the precision of treatment effect estimates when the proportion of missingness is not too large and the adjusted covariate is associated with the outcome. Furthermore, we underscore the importance of including the missingness indicators as predictors in the outcome model or the propensity score model especially when covariates are missing not at random.