Properties and pitfalls of weighting as an alternative to multilevel multiple imputation in cluster randomized trials...

The generalized estimating equation (GEE) approach can be used to analyze cluster randomized trial data to obtain population-averaged intervention effects. However, most cluster randomized trials have some missing outcome data and a GEE analysis of available data may be biased when outcome data are not missing completely at random. Although multilevel multiple imputation for GEE (MMI-GEE) has been widely used, alternative approaches such as weighted GEE are less common in practice. Using both simulations and a real data example, we evaluate the performance of inverse probability weighted GEE vs. MMI-GEE for binary outcomes. Simulated data are generated assuming a covariate-dependent missing data pattern across a range of missingness clustering (from none to high), where all covariates are measured at baseline and are fully observed (i.e. a type of missing-at-random mechanism). Two types of weights are estimated and used in the weighted GEE: (1) assuming no clustering of missingness (W-GEE) and (2) accounting for such clustering (CW-GEE). Results show that, even in settings with high missingness clustering, CW-GEE can lead to more bias and lower coverage than W-GEE, whereas W-GEE and MMI-GEE provide comparable results. W-GEE should be considered a viable strategy to account for missing outcomes in cluster randomized trials.