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Accounting for variation in the required sample size in the design of group-sequential trials

Grayling, Michael J. and Mander, Adrian P. 2021. Accounting for variation in the required sample size in the design of group-sequential trials. Contemporary Clinical Trials 107 , 106459. 10.1016/j.cct.2021.106459

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Introduction Most literature on optimal group-sequential designs focuses on minimising the expected sample size. We highlight other factors for consideration. Methods We discuss several quantities less-often considered in adaptive design: the median and standard deviation of the random required sample size, and the probability of committing an interim error. We consider how the optimal timing of interim analyses changes when these quantities are accounted for. Results Incorporating the standard deviation of the required sample size into an optimality framework, we demonstrate how and when this quantity means using a group-sequential approach is not optimal. The optimal timing of an interim analysis is shown to be highly dependent on the pre-specified preference for minimising the expected sample size relative to its standard deviation. Conclusions Examining multiple factors, which measure the advantages and disadvantages of group-sequential designs, helps determine the best design for a specific trial.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Centre for Trials Research (CNTRR)
Additional Information: This is an open access article under the CC BY license (
Publisher: Elsevier
ISSN: 1551-7144
Date of First Compliant Deposit: 19 August 2021
Date of Acceptance: 26 May 2021
Last Modified: 20 Aug 2021 09:15

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