4.5 Article

Interval estimation for drop-the-losers designs

期刊

BIOMETRIKA
卷 97, 期 2, 页码 405-418

出版社

OXFORD UNIV PRESS
DOI: 10.1093/biomet/asq003

关键词

Adaptive design; Clinical trial; Drop-the-losers design; p-value combination; Two-stage test

资金

  1. National Science Foundation, U.S.A

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In the first stage of a two-stage, drop-the-losers design, a candidate for the best treatment is selected. At the second stage, additional observations are collected to decide whether the candidate is actually better than the control. The design also allows the investigator to stop the trial for ethical reasons at the end of the first stage if there is already strong evidence of futility or superiority. Two types of tests have recently been developed, one based on the combined means and the other based on the combined p-values, but corresponding interval estimators are unavailable except in special cases. The problem is that, in most cases, the interval estimators depend on the mean configuration of all treatments in the first stage, which is unknown. In this paper, we prove a basic stochastic ordering lemma that enables us to bridge the gap between hypothesis testing and interval estimation. The proposed confidence intervals achieve the nominal confidence level in certain special cases. Simulations show that decisions based on our intervals are usually more powerful than those based on existing methods.

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