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

Abstract

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.