Dealing with missing observations in the outcome and covariates in randomized controlled trials

This article compares different missing data methods in randomized controlled trials, specifically addressing cases involving joint missingness in the outcome and covariates. In the existing literature, it is still unclear how advanced methods like linear mixed model (LMM) and multiple imputation (MI) perform in comparison to simpler methods regarding the estimation of treatment effects and their standard errors. We therefore evaluates the performance of LMM and MI against simple alternatives across a wide range of simulation scenarios for various realistic missingness mechanisms. The results show that no single method universally outperforms the others. However, LMM followed by MI demonstrates superior performance across most missingness scenarios. Interestingly, a simple method that combines complete case analysis for the missing outcome and mean imputation for the missing covariate (CCAME) performs similarly to LMM and MI. All methods are furthermore compared in the context of a randomized controlled trial on chronic obstructive pulmonary disease.