Information content of stepped wedge designs under the working independence assumption

Abstract

The stepped wedge design is increasingly popular in pragmatic trials and implementation science research studies for evaluating system-level interventions that are perceived to be beneficial to patient populations. An important step in planning a stepped wedge design is to understand the efficiency of the treatment effect estimator and hence the power of the study. We develop several novel analytical results for designing stepped wedge cluster randomized trials analyzed through generalized estimating equations under a misspecified working independence correlation structure. We first contribute a general variance expression of the treatment effect estimator when data collection is scheduled for each cluster-period. Because resource and patient-centered considerations may intentionally call for an incomplete design with outcome data being omitted for certain cluster-periods, we further derive the information content based on the robust sandwich variance to identify data elements that may be preferentially omitted with minimum loss of precision in estimating the treatment effect. We prove that centrosymmetric pairs of cluster-periods, treatment sequences and periods have identical information content and thus contribute equally to the treatment effect estimation, as long as the true covariance structure for the cluster-period means remains centrosymmetric. Finally, we provide an example of how to obtain an incomplete stepped wedge design that admits a more efficient independence GEE estimator but requires less data collection effort. Our results elegantly extend existing ones from linear mixed models coupled with model-based variances to accommodate a misspecified independence working correlation structure through the robust sandwich variances.