Interval Estimation in Two-Stage, Drop-the-Losers Clinical Trials with Flexible Treatment Selection

• Activity Number: 408
• Type: Contributed
• Date/Time: Tuesday, August 3, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Dan Neal*+ and George Casella and Mark Yang and Samuel S. Wu+
• Companies: University of Florida and University of Florida and University of Florida and University of Florida
• Keywords: Flexible selection ; clinical trial ; drop-the-losers design ; p-value combination ; two-stage test

Abstract

In a two-stage, drop-the-losers clinical trial, the ``best" among a number of treatments is chosen at an interim analyis after the first stage. The selected treatment continues into the second stage for confirmation of efficacy while the remaining treatments (the ``losers") are dropped from the study. Wu et al.(Biometrika, in press) showed how to construct confidence limits for the mean difference between the selected treatment and the control when the treatment is chosen based on highest efficacy in the primary clinical endpoint. 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, or any other 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.