Analysis of Stepped‐Wedge Cluster Randomized Trials: A Tutorial Using Marginal Models
Year: 2026
Type: article
Abstract: Stepped-wedge cluster randomized trials (SW-CRTs) are one-way crossover trials that randomize clusters (i.e., groups) of individuals to the time point (period) at which an intervention is introduced into the cluster. In these designs, the intervention under evaluation is introduced into all of the clusters by the end of the study in a series of "steps." Analysis of SW-CRTs using marginal models provides a population-averaged interpretation of the estimated intervention effect and flexible specification of the within-cluster, marginal pairwise association structure; the latter has practical application in reporting intraclass (i.e., pairwise) correlations and calculating power for CRTs. Despite these features, use of marginal modeling of SW-CRTs has been mostly limited to applications with working independence and simple exchangeable correlation structures that are suboptimal for multi-period CRTs when correlation among responses decays over time. However, there have been many methodological developments in marginal modeling of SW-CRTs over the past fifteen years, particularly on (i) multi-parameter, within-cluster correlation structures; (ii) paired generalized estimating equations (GEE) for simultaneous estimation of mean and correlation parameters with standard errors; and, when the number of clusters is small, (iii) corrections to reduce the bias of variance estimators, and that of correlation estimates using matrix-adjusted estimating equations (MAEE). The goal of the current tutorial is to survey these newer developments and to provide case studies to enable applied researchers to implement GEE/MAEE for marginal model analysis of SW-CRTs, with application to both cohorts and designs with repeated cross-sectional samples. The methods are also applicable to multi-period, parallel-arm and cluster-crossover CRTs.
Source: Statistics in Medicine
DOI: 10.1002/sim.70393
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,450
Funders: American Heart Association, Claneil Foundation, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Society of Systematic Biologists, Patient-Centered Outcomes Research Institute, Honorable Tina Brozman Foundation, University of Minnesota, Alzheimer Forschung Initiative, Botanical Society of America, BC Children’s Hospital Foundation, Belinda Sue Fund for Ovarian Cancer Awareness and Research, Innovationsfonden, Ovarian Cancer Research Fund Alliance, Ministerio de Ciencia, Innovación y Universidades, Arnold Ventures, Agenția Națională pentru Cercetare și Dezvoltare, Badan Riset dan Inovasi Nasional, Cancer Research UK, Guy's and St Thomas' Charity, European Commission, Hort Innovation, Agency for Science, Technology and Research, National Research Foundation Singapore, Nanyang Technological University, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, National Natural Science Foundation of China, Grantová Agentura České Republiky, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Austrian Science Fund, Generalitat de Catalunya, Consejo Nacional de Investigaciones Científicas y Técnicas, Bundesministerium für Gesundheit, Ministero dell’Istruzione, dell’Università e della Ricerca, Fritz Thyssen Stiftung, National Research Foundation of Korea, Hjärnfonden, King Fahd University of Petroleum and Minerals, Qatar University, Sapienza Università di Roma, Javna Agencija za Raziskovalno Dejavnost RS, Vetenskapsrådet, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, Mitacs, Kasetsart University, Financiadora de Estudos e Projetos, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Sächsische Aufbaubank, Qassim University, Chongqing Municipal Education Commission, Universidade Estadual Paulista, Novo Nordisk Fonden, Korea Institute of Marine Science and Technology promotion, Lembaga Pengelola Dana Pendidikan, Imam Abdulrahman Bin Faisal University, Fundación Palarq, Ministry of Higher Education, Science, Research and Innovation, Thailand, Thailand Science Research and Innovation, Rajamangala University of Technology Phra Nakhon, William Demant Fonden, National Institutes of Health, Qatar National Research Fund, Qatar National Library, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Natural Environment Research Council, Health Research Council of New Zealand, Japan Society for the Promotion of Science, Agencia Estatal de Investigación, National Key Research and Development Program of China, Faculty of Medicine Siriraj Hospital, Mahidol University, National Institute on Aging, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Dental and Craniofacial Research, Division of Computing and Communication Foundations, Division of Environmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, HORIZON EUROPE European Innovation Council, Weleda
OpenAlex ID: W7138901729