Analysis of Stepped-Wedge Randomised Cluster Trial using a generalized pairwise comparison approach : a simulation study

TL;DR

This simulation study evaluates various generalized pairwise comparison methods for analyzing stepped-wedge cluster randomized trials, identifying the most reliable approaches considering clustering, temporal trends, and correlation structures.

Contribution

The paper compares and identifies the most effective GPC-based estimators for SW-CRTs, providing practical guidance for their application in complex trial settings.

Findings

Hierarchical mixed-effects model (b4) and cluster-restricted PIM (c2) maintain error control.

c2 generally shows higher efficiency, especially under strong clustering.

Both methods perform similarly for large treatment effects.

Abstract

Stepped-wedge cluster randomised trials (SW-CRTs) increasingly evaluate complex interventions, yet methodological guidance for analysing composite endpoints using generalized pairwise comparisons (GPC)remains limited. This work investigates the performance of several GPC-based estimators in the presence of clustering, temporal trends, and varying correlation structures typical of SW-CRTs. We conducted an extensive simulation study covering a range of intraclass correlations (ICC), cluster autocorrelation coefficients (CAC), time effects, and treatment effect sizes. Eight analytical approaches were compared, including unadjusted estimators, cluster-stratified win odds, mixed-effects models applied to cluster-period win odds, and probabilistic index models (PIMs). Type I error control was strongly compromised for methods ignoring time or clustering, whereas only two approaches consistently maintained nominal error rates: a hierarchical mixed-effects model with sequence and cluster-level random slopes (b4) and a cluster-restricted PIM (c2). These two methods were further evaluated in terms of statistical power, where c2 generally showed higher efficiency, particularly under strong clustering, low CAC, or the presence of temporal trends, while both converged to similar performance for large treatment effects. Overall, our findings identify b4 and c2 as the most reliable GPC-based strategies for SW-CRT analysis and provide practical guidance for their application, including for ongoing trials such as ETHER.