Novel methods for the analysis of stepped wedge cluster randomized trials

Stat Med. 2020 Mar 30;39(7):815-844. doi: 10.1002/sim.8451. Epub 2019 Dec 26.

Abstract

Stepped wedge cluster randomized trials (SW-CRTs) have become increasingly popular and are used for a variety of interventions and outcomes, often chosen for their feasibility advantages. SW-CRTs must account for time trends in the outcome because of the staggered rollout of the intervention. Robust inference procedures and nonparametric analysis methods have recently been proposed to handle such trends without requiring strong parametric modeling assumptions, but these are less powerful than model-based approaches. We propose several novel analysis methods that reduce reliance on modeling assumptions while preserving some of the increased power provided by the use of mixed effects models. In one method, we use the synthetic control approach to find the best matching clusters for a given intervention cluster. Another method makes use of within-cluster crossover information to construct an overall estimator. We also consider methods that combine these approaches to further improve power. We test these methods on simulated SW-CRTs, describing scenarios in which these methods have increased power compared with existing nonparametric methods while preserving nominal validity when mixed effects models are misspecified. We also demonstrate theoretical properties of these estimators with less restrictive assumptions than mixed effects models. Finally, we propose avenues for future research on the use of these methods; motivation for such research arises from their flexibility, which allows the identification of specific causal contrasts of interest, their robustness, and the potential for incorporating covariates to further increase power. Investigators conducting SW-CRTs might well consider such methods when common modeling assumptions may not hold.

Keywords: cluster randomized trials; mixed effects models; permutation tests; stepped wedge; synthetic control.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cluster Analysis
  • Cross-Over Studies
  • Humans
  • Randomized Controlled Trials as Topic
  • Research Design*