Randomization-based inference for a marginal treatment effect in stepped wedge cluster randomized trials

Stat Med. 2021 Sep 10;40(20):4442-4456. doi: 10.1002/sim.9040. Epub 2021 May 21.

Abstract

In a cross-sectional stepped wedge cluster randomized trial (SWT), clusters are randomized to crossover from control to intervention at different time periods and outcomes are assessed for a different set of individuals in each cluster-period. Randomization-based inference is an attractive analysis strategy for SWTs because it does not require full parametric specification of the outcome distribution or correlation structure and its validity does not rely on having a large number of clusters. Existing randomization-based approaches for SWTs, however, either focus on hypothesis testing and omit technical details on confidence interval (CI) calculation with noncontinuous outcomes, or employ weighted cluster-period summary statistics for p-value and CI calculation, which can result in suboptimal efficiency if weights do not incorporate information on varying cluster-period sizes. In this article, we propose a framework for calculating randomization-based p-values and CIs for a marginal treatment effect in SWTs by using test statistics derived from individual-level generalized linear models. We also investigate how study design features, such as stratified randomization, subsequently impact various SWT analysis methods including the proposed approach. Data from the XpertMTB/RIF tuberculosis trial are reanalyzed to illustrate our method and compare it to alternatives.

Keywords: confidence interval; permutation test; randomization-based inference; stepped wedge cluster randomized trial; stratified randomization.

Publication types

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

MeSH terms

  • Cluster Analysis
  • Cross-Sectional Studies
  • Humans
  • Models, Statistical*
  • Random Allocation
  • Randomized Controlled Trials as Topic
  • Research Design*
  • Sample Size