Maintaining the validity of inference from linear mixed models in stepped-wedge cluster randomized trials under misspecified random-effects structures

Linear mixed models are commonly used in analyzing stepped-wedge cluster randomized trials (SW-CRTs). A key consideration for analyzing a SW-CRT is accounting for the potentially complex correlation structure, which can be achieved by specifying a random effects structure. Common random effects structures for a SW-CRT include random intercept, random cluster-by-period, and discrete-time decay. Recently, more complex structures, such as the random intervention structure, have been proposed. In practice, specifying appropriate random effects can be challenging. Robust variance estimators (RVE) may be applied to linear mixed models to provide consistent estimators of standard errors of fixed effect parameters in the presence of random-effects misspecification. However, there has been no empirical investigation of RVE for SW-CRT. In this paper, we first review five RVEs (both standard and small-sample bias-corrected RVEs) that are available for linear mixed models. We then describe a comprehensive simulation study to examine the performance of these RVEs for SW-CRTs with a continuous outcome under different data generators. For each data generator, we investigate whether the use of a RVE with either the random intercept model or the random cluster-by-period model is sufficient to provide valid statistical inference for fixed effect parameters, when these working models are subject to misspecification. Our results indicate that the random intercept and random cluster-by-period models with RVEs performed similarly. The CR3 RVE estimator, coupled with the number of clusters minus two degrees of freedom correction, consistently gave the best coverage results, but could be slightly anti-conservative when the number of clusters was below 16. We summarize the implications of our results for linear mixed model analysis of SW-CRTs in practice.