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Estimation in flexible two stage designs
Author(s) -
Brannath Werner,
König Franz,
Bauer Peter
Publication year - 2006
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.2258
Subject(s) - sample size determination , computer science , confidence interval , statistics , a priori and a posteriori , adaptive design , interim , type i and type ii errors , null hypothesis , point estimation , interval estimation , statistical hypothesis testing , range (aeronautics) , data mining , mathematics , clinical trial , medicine , philosophy , materials science , archaeology , epistemology , pathology , composite material , history
Adaptive test designs for clinical trials allow for a wide range of data driven design adaptations using all information gathered until an interim analysis. The basic principle is to use a test statistics which is invariant with respect to the design adaptations under the null hypothesis. This allows for a control of the type I error rate for the primary hypothesis even for adaptations not specified a priori in the study protocol. Estimation is usually another important part of a clinical trial, however, is more difficult in adaptive designs. In this research paper we give an overview of point and interval estimates for flexible designs and compare methods for typical sample size rules. We also make some proposals for confidence intervals which have nominal coverage probability also after an unforeseen design adaptation and which contain the maximum likelihood estimate and the usual unadjusted confidence interval. Copyright © 2005 John Wiley & Sons, Ltd.