Subgroup Analyses in Stepped-Wedge Cluster Randomized Trials: A Systematic Review of Statistical Practice and Reporting from 2016 to 2023.

Authors

Guangyu Tong, Changjun Li, Hao Wang, Xi Fang, Ruyi Liu, Yukang Zeng, Qianzhe Sun, Yongdong Ouyang, Mary Ryan Baumann, Kendra Davis-Plourde, Zehui Wang, Fan Li, Monica Taljaard

Published in

Journal of clinical epidemiology. Pages 112512. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

Subgroup analyses can inform whether intervention effects differ systematically across participants, but they are prone to false-positive findings, low power, and selective reporting. Stepped-wedge cluster randomized trials (SW-CRTs) introduce additional inferential complexities (e.g., time effects, clustering, complex interactions) yet subgroup-analysis practice in SW-CRTs has not been systematically evaluated. Our objectives were to describe: (1) the prevalence and extent of subgroup analyses; (2) characteristics of the subgroup variables of interest; (3) adherence to key recommendations such as pre-specification and justification; (4) statistical approaches used; and (5) details of reporting results.
We reviewed primary reports of completed health-related SW-CRTs from a 2016-2023 database to capture statistical and reporting practice. Trials were eligible if they had at least two sequences, three periods, and randomized at least 5 clusters. Two independent reviewers extracted information from each trial and reached consensus through discussion. Results were summarized using median (interquartile ranges) and frequencies (%).
Of 211 eligible reports, 99 (47%) presented results of at least one subgroup analysis; the median number of subgroup analyses (unique outcome by covariate combinations) per trial was 4 (Q1-Q3:2-8; range:1-81). Only 23 (23%) clearly prespecified all presented subgroup analyses. A rationale for all subgroup analyses was provided in 28 (28%), while 53 (54%) provided none. Stratified analyses were common (n=79, 80%); the use of interaction testing was reported in 49 (50%), but only 35 (35%) reported an interaction test result with the treatment indicator. Power calculations for subgroup analyses were rare (n=4, 4%), and multiplicity corrections were uncommon (n=2, 2%). At least one statistically significant stratum-specific treatment effect was observed in 69 (70%) trials.
Subgroup analyses are common in SW-CRTs but are frequently under-specified and inconsistently analyzed and reported, with limited interaction testing, minimal power justification, and rare adjustment for multiple testing. These patterns are broadly consistent with concerns identified in prior subgroup-analysis reviews of randomized trials, suggesting that longstanding vulnerabilities persist in SW-CRTs and may be compounded by design complexity. More explicit, design-aware guidance for planning, analysis, and reporting of subgroup investigations in SW-CRTs may improve the credibility and interpretability of subgroup findings.

PMID:
42753990
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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