Mixed-effects models for the design and analysis of stepped wedge cluster randomized trials: An overview

Stat Methods Med Res. 2021 Feb;30(2):612-639. doi: 10.1177/0962280220932962. Epub 2020 Jul 6.


The stepped wedge cluster randomized design has received increasing attention in pragmatic clinical trials and implementation science research. The key feature of the design is the unidirectional crossover of clusters from the control to intervention conditions on a staggered schedule, which induces confounding of the intervention effect by time. The stepped wedge design first appeared in the Gambia hepatitis study in the 1980s. However, the statistical model used for the design and analysis was not formally introduced until 2007 in an article by Hussey and Hughes. Since then, a variety of mixed-effects model extensions have been proposed for the design and analysis of these trials. In this article, we explore these extensions under a unified perspective. We provide a general model representation and regard various model extensions as alternative ways to characterize the secular trend, intervention effect, as well as sources of heterogeneity. We review the key model ingredients and clarify their implications for the design and analysis. The article serves as an entry point to the evolving statistical literatures on stepped wedge designs.

Keywords: Cluster randomized trials; group-randomized trials; heterogeneity; intraclass correlation coefficient; mixed-effects regression; pragmatic clinical trials; sample size calculation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cluster Analysis
  • Cross-Over Studies
  • Models, Statistical*
  • Randomized Controlled Trials as Topic
  • Research Design*