The first two authors (in alphabetic order) have made equal contributions to this paper.
Selection and bias—Two hostile brothers
Article first published online: 20 OCT 2009
Copyright © 2009 John Wiley & Sons, Ltd.
Statistics in Medicine
Volume 29, Issue 1, pages 1–13, 15 January 2010
How to Cite
Bauer, P., Koenig, F., Brannath, W. and Posch, M. (2010), Selection and bias—Two hostile brothers. Statist. Med., 29: 1–13. doi: 10.1002/sim.3716
- Issue published online: 15 DEC 2009
- Article first published online: 20 OCT 2009
- Manuscript Accepted: 28 JUL 2009
- Manuscript Received: 9 OCT 2008
- FWF. Grant Number: P18698-N15
- many one comparison;
- treatment selection;
- mean bias;
- mean square error;
- admission bias;
- sample size reassessment
We consider the situation where in a first stage of a clinical trial several treatments are compared with a single control and the ‘best’ treatment(s) are selected in an interim analysis to be carried on to the second stage. We quantify the mean bias and mean square error of the conventional estimates after selection depending on the number of treatments and the selection time during the trial. The cases without or with reshuffling the planned sample size of the dropped treatments to the selected ones are investigated. The mean bias shows very different patterns depending on the selection rule and the unknown parameter values. We stress the fact that the quantification of the bias is possible only in designs with planned adaptivity where the design allows reacting to new evidence, but the decision rules are laid down in advance. Finally, we calculate the mean bias which arises in a simple but influential regulatory selection rule, to register a new medical therapy only when two pivotal trials have both proven an effect by a statistical test. Copyright © 2009 John Wiley & Sons, Ltd.