Guidance for Addressing Individual Time Effects in Cohort Stepped Wedge Cluster Randomized Trials: A Simulation Study
Background: Stepped wedge cluster randomized trials (SW-CRTs) involve sequential measurements within clusters over time. Initially, all clusters start in the control condition before crossing over to the intervention on a staggered schedule. In cohort designs, secular trends, cluster-level changes, and individual-level changes (e.g., aging) must be considered. Methods: We performed a Monte Carlo simulation to analyze the influence of different time effects on the estimation of the intervention effect in cohort SW-CRTs. We compared four linear mixed models with different adjustment strategies, all including random intercepts for clustering and repeated measurements. We recorded the estimated fixed intervention effects and their corresponding model-based standard errors, derived from models both without and with cluster-robust variance estimators (CRVEs). Results: Models incorporating fixed categorical time effects, a fixed intervention effect, and two random intercepts provided unbiased estimates of the intervention effect in both closed and open cohort SW-CRTs. Fixed categorical time effects captured temporal cohort changes, while random individual effects accounted for baseline differences. However, these differences can cause large, non-normally distributed random individual effects. CRVEs provide reliable standard errors for the intervention effect, controlling the Type I error rate. Conclusions: Our simulation study is the first to assess individual-level changes over time in cohort SW-CRTs. Linear mixed models incorporating fixed categorical time effects and random cluster and individual effects yield unbiased intervention effect estimates. However, cluster-robust variance estimation is necessary when time-varying independent variables exhibit nonlinear effects. We recommend always using CRVEs.