Planning stepped wedge cluster randomized trials to detect treatment effect heterogeneity

Abstract

Stepped wedge design is a popular research design that enables a rigorous evaluation of candidate interventions by using a staggered cluster randomization strategy. While analytical methods were developed for designing stepped wedge trials, the prior focus has been solely on testing for the average treatment effect. With a growing interest on formal evaluation of the heterogeneity of treatment effects across patient subpopulations, trial planning efforts need appropriate methods to accurately identify sample sizes or design configurations that can generate evidence for both the average treatment effect and variations in subgroup treatment effects. To fill in that important gap, this article derives novel variance formulas for confirmatory analyses of treatment effect heterogeneity, that are applicable to both cross‐sectional and closed‐cohort stepped wedge designs. We additionally point out that the same framework can be used for more efficient average treatment effect analyses via covariate adjustment, and allows the use of familiar power formulas for average treatment effect analyses to proceed. Our results further sheds light on optimal design allocations of clusters to maximize the weighted precision for assessing both the average and heterogeneous treatment effects. We apply the new methods to the Lumbar Imaging with Reporting of Epidemiology Trial, and carry out a simulation study to validate our new methods.