This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Zou, G. Y. Articles by Klar, N. Search for Related Content PubMed PubMed Citation Articles by Zou, G. Y. Articles by Klar, N. Pubmed/NCBI databases Medline Plus Health Information Clinical Trials Social Bookmarking                         What's this?

Group sequential methods for cluster randomization trials with binary outcomes

Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada N6A 5K8; gzou{at}robarts.ca; Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada

Allan Donner

Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada; Robarts Clinical Trials, Robarts Research Institute, London, Ontario, Canada

Neil Klar

Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada

Background Cluster randomization trials in which intact social units are randomly assigned to different intervention groups have become very popular in recent years, particularly for the evaluation of innovations in the delivery of health care. An extensive literature dealing with the associated methodological challenges has also appeared. Although the monitoring of such trials using formal stopping rules is clearly indicated when the outcomes are irreversible and individual-level data are available sequentially, simple and reliable statistical methods that may be used for this purpose are currently not available.

Purpose To investigate the validity of standard group sequential methods when applied to cluster randomization trials having binary outcomes.

Methods The large sample distributions for each of five test statistics computed from sequentially accumulated data are derived. A simulation study is performed to evaluate the finite sample properties of these statistics when applied to the interim analysis of cluster randomization trials. Data from the World Health Organization antenatal care trial [1] are used to illustrate the methods.

Results Each of the joint distributions is shown to be characterized by a covariance structure that asymptotically satisfies an independent increments structure, a foundation that simplifies group sequential methods [2]. The simulation study reveals that four of the five test statistics evaluated provide satisfactory performance with as few as 10 clusters allocated to each of two interventions.

Limitations The applicability of our results to effect estimation following a group sequential cluster randomization trial is not investigated, although a theoretical foundation which may be used for this purpose is presented.

Conclusions Standard group sequential methods can be applied to cluster randomization trials when interim analyses are warranted.

Clinical Trials, Vol. 2, No. 6, 479-487 (2005)
DOI: 10.1191/1740774505cn126oa


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?