Dynamic balanced randomization for clinical trials

D. F. Signorini*, O. Leung, R. J. Simes, E. Beller, V. J. Gebski, T. Callaghan

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

117 Citations (Scopus)

Abstract

Common methods of treatment allocation for multi‐centre and/or stratified randomized clinical trials can result in substantial differences between the number of patients allocated to each treatment arm. This can occur in the overall trial for a permuted block design or within individual institutions/strata when using a minimization scheme. This may lead to a bias in the result. Also, these procedures can be predictable, with the possibility of an investigator‐introduced selection bias. An easily implemented method of randomization is proposed which attempts to overcome these problems by balancing treatment allocations both within strata and across the trial as a whole. The method keeps a running tally on total treatment allocation numbers at all stratification levels. When a patient accrues a hierarchical decision rule is applied, and the allocation is deterministic if certain pre‐defined limits are exceeded, and random otherwise. The method is an extension of the big stick design of Soares and Wu, and is related to both Zelen's key number randomization methods and the schemes of Nordle and Brantmark. Simulation studies are used to demonstrate that major imbalances possible with other schemes do not occur using this method, and that the potential for selection bias is much reduced.

Original languageEnglish
Pages (from-to)2343-2350
Number of pages8
JournalStatistics in Medicine
Volume12
Issue number24
DOIs
Publication statusPublished - 30 Dec 1993
Externally publishedYes

Fingerprint

Dive into the research topics of 'Dynamic balanced randomization for clinical trials'. Together they form a unique fingerprint.

Cite this