title: Sample size calculations for the design of cluster randomized trials: A summary of methodology.
abstract: Cluster randomized trial designs are growing in popularity in, for example, cardiovascular medicine research and other clinical areas and parallel statistical developments concerned with the design and analysis of these trials have been stimulated. Nevertheless, reviews suggest that design issues associated with cluster randomized trials are often poorly appreciated and there remain inadequacies in, for example, describing how the trial size is determined and the associated results are presented. In this paper, our aim is to provide pragmatic guidance for researchers on the methods of calculating sample sizes. We focus attention on designs with the primary purpose of comparing two interventions with respect to continuous, binary, ordered categorical, incidence rate and time-to-event outcome variables. Issues of aggregate and non-aggregate cluster trials, adjustment for variation in cluster size and the effect size are detailed. The problem of establishing the anticipated magnitude of between- and within-cluster variation to enable planning values of the intra-cluster correlation coefficient and the coefficient of variation are also described. Illustrative examples of calculations of trial sizes for each endpoint type are included.
authors.affiliation: National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore 169609; Center for Quantitative Medicine, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857. Electronic address: gao.fei@nhcs.com.sg.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Center for Quantitative Medicine, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857; Department of Epidemiology and Preventive Medicine, Monash University, Level 6, The Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia. Electronic address: arul_earnest@hotmail.com.
authors.forename: Arul
authors.initials: A
authors.lastname: Earnest
authors.affiliation: Health Services & Systems Research, Duke-NUS Graduate Medical School, 8 College Road\, 169857, Singapore; Department of Medicine (General Internal Medicine), Duke University Medical Center, 411 W. Chapel Hill Street, Suite 500, Durham, NC 27701, USA. Electronic address: david.matchar@duke-nus.edu.sg.
authors.forename: David B
authors.initials: DB
authors.lastname: Matchar
authors.affiliation: Medical Statistics Group, School of Health and Related Research, University of Sheffield, Regents Court, 30 Regent Street, Sheffield S1 4DA, UK. Electronic address: m.j.campbell@sheffield.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Campbell
authors.affiliation: Medical Statistics Group, School of Health and Related Research, University of Sheffield, Regents Court, 30 Regent Street, Sheffield S1 4DA, UK; Department of Cancer Studies and Molecular Medicine, Clinical Sciences Building, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK. Electronic address: dm113@leicester.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Machin
mesh_terms: D003153:Community Health Services / Q000458:organization & administration; D015438:Health Behavior; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size
keywords: Cluster randomized trial; Intra-class correlation; Sample size