Interval estimation in two-stage, drop-the-losers clinical trials with flexible treatment selection

In a two‐stage, drop‐the‐losers clinical trial, researchers choose the ‘best’ among a number of treatments at an interim analysis after the first stage. The selected treatment continues to the second stage for confirmation of efficacy, and the remaining treatments (the ‘losers’) are dropped from the...

Full description

Saved in:
Bibliographic Details
Published inStatistics in medicine Vol. 30; no. 23; pp. 2804 - 2814
Main Authors Neal, Dan, Casella, George, Yang, Mark C. K., Wu, Samuel S.
Format Journal Article
LanguageEnglish
Published Chichester, UK John Wiley & Sons, Ltd 15.10.2011
Wiley Subscription Services, Inc
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:In a two‐stage, drop‐the‐losers clinical trial, researchers choose the ‘best’ among a number of treatments at an interim analysis after the first stage. The selected treatment continues to the second stage for confirmation of efficacy, and the remaining treatments (the ‘losers’) are dropped from the study. Wu et al. (Biometrika 2010; 97:405–418) showed how to construct confidence limits for the mean difference between the selected treatment and the control when the treatment is chosen after the first stage based on the highest efficacy in the primary clinical endpoint. In this article, we show how to construct a lower confidence limit for the mean difference when the treatment is chosen based on first‐stage safety data, early endpoint efficacy data, a combination of safety and efficacy data or any other prespecified selection rule. The result extends the applicability of drop‐the‐losers designs, for in practice, the ‘best’ treatment often is not chosen for efficacy alone. Copyright © 2011 John Wiley & Sons, Ltd.
Bibliography:ArticleID:SIM4308
istex:6E7804C7FB8E1EE4D0DD13D06CC74D2B6E9B4D7F
ark:/67375/WNG-1FNFCX2Z-0
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0277-6715
1097-0258
DOI:10.1002/sim.4308