Browse by author
Lookup NU author(s): Professor James WasonORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Two-stage trial designs provide the flexibility to stop early for efficacy or futility and are popular because they have a smaller sample size on average than a traditional trial has with the same type I and II error rates. This makes them financially attractive but also has the ethical benefit of reducing, in the long run, the number of patients who are given ineffective treatments. Designs that minimise the expected sample size are often referred to as 'optimal'. However, two-stage designs can impart a substantial bias into the parameter estimate at the end of the trial. In this paper, we argue that the expected performance of one's chosen estimation method should also be considered when deciding on a two-stage trial design. We review the properties of standard and bias-adjusted maximum likelihood estimators as well as mean and median unbiased estimators. We then identify optimal two-stage design and analysis procedures that balance projected sample size considerations with those of estimator performance. We make available software to implement this new methodology. © 2012 John Wiley & Sons, Ltd.
Author(s): Bowden J, Wason J
Publication type: Article
Publication status: Published
Journal: Statistics in Medicine
Year: 2012
Volume: 31
Issue: 29
Pages: 3874-3884
Print publication date: 20/12/2012
Online publication date: 11/07/2012
ISSN (print): 0277-6715
ISSN (electronic): 1097-0258
Publisher: John Wiley & Sons Ltd
URL: https://doi.org/10.1002/sim.5468
DOI: 10.1002/sim.5468
PubMed id: 22786815
Altmetrics provided by Altmetric