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Special Issue Paper
Article first published online: 27 JUN 2012
Published 2012. This article is a US Government work and is in the public domain in the USA.
Statistics in Medicine
Special Issue: Papers from the 32nd Annual Conference of the International Society for Clinical Biostatistics
Volume 31, Issue 30, pages 4146–4153, 30 December 2012
How to Cite
Posch, M. and Proschan, M. A. (2012), Unplanned adaptations before breaking the blind. Statist. Med., 31: 4146–4153. doi: 10.1002/sim.5361
- Issue published online: 10 DEC 2012
- Article first published online: 27 JUN 2012
- Manuscript Accepted: 4 FEB 2012
- Manuscript Received: 30 SEP 2011
- Austrian Science Fund (FWF). Grant Number: P23167
- adaptive methods;
- permutation tests;
- type I error rate control;
- multiple comparisons;
- blinded interim analysis
Occasionally, things go so wrong in a clinical trial that a change must be made. For example, the originally planned primary outcome may be measured completely unreliably. Is there any recourse? One may still be able to salvage the trial using a permutation test if a change is made before breaking the treatment blind. The solution is not a panacea; we discuss the limitations and legitimate grounds for criticism. Still, when it is needed, the procedure is preferable to rigid adherence to a design that makes no sense. Published 2012. This article is a US Government work and is in the public domain in the USA.