Impact of unequal cluster sizes for GEE analyses of stepped wedge cluster randomized trials with binary outcomes.

The stepped wedge (SW) design is a type of unidirectional crossover design where cluster units switch from control to intervention condition at different prespecified time points. While a convention in study planning is to assume the cluster-period sizes are identical, SW cluster randomized trials (SW-CRTs) involving repeated cross-sectional designs frequently have unequal cluster-period sizes, which can impact the efficiency of the treatment effect estimator. In this paper, we provide a comprehensive investigation of the efficiency impact of unequal cluster sizes for generalized estimating equation analyses of SW-CRTs, with a focus on binary outcomes as in the Washington State Expedited Partner Therapy trial. Several major distinctions between our work and existing work include the following: (i) we consider multilevel correlation structures in marginal models with binary outcomes; (ii) we study the implications of both the between-cluster and within-cluster imbalances in sizes; and (iii) we provide a comparison between the independence working correlation versus the true working correlation and detail the consequences of ignoring correlation estimation in SW-CRTs with unequal cluster sizes. We conclude that the working independence assumption can lead to substantial efficiency loss and a large sample size regardless of cluster-period size variability in SW-CRTs, and recommend accounting for correlations in the analysis. To improve study planning, we additionally provide a computationally efficient search algorithm to estimate the sample size in SW-CRTs accounting for unequal cluster-period sizes, and conclude by illustrating the proposed approach in the context of the Washington State study.

Duke Scholars

Author Elizabeth Louise Turner Biostatistics & Bioinformatics, Division of Biostatistics