Confirmatory adaptive designs with Bayesian decision tools for a targeted therapy in oncology.

Full Abstract

The ability to select a sensitive patient population may be crucial for the development of a targeted therapy. Identifying such a population with an acceptable level of confidence may lead to an inflation in development time and cost. We present an approach that allows to decrease these costs and to increase the reliability of the population selection. It is based on an actual adaptive phase II/III design and uses Bayesian decision tools to select the population of interest at an interim analysis. The primary endpoint is assumed to be the time to some event like e.g. progression. It is shown that the use of appropriately stratified logrank tests in the adaptive test procedure guarantees overall type I error control also when using information on patients that are censored at the adaptive interim analysis. The use of Bayesian decision tools for the population selection decision making is discussed. Simulations are presented to illustrate the operating characteristics of the study design relative to a more traditional development approach. Estimation of treatment effects is considered as well. Copyright (c) 2009 John Wiley & Sons, Ltd.

Author information

Author/s: Brannath, Werner (W); Zuber, Emmanuel (E); Branson, Michael (M); Bretz, Frank (F); Gallo, Paul (P); Posch, Martin (M); Racine-Poon, Amy (A);

Affiliation: Medical University of Vienna, Vienna, Austria.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Statistics in medicine (Stat Med), published in England. (Language: eng)

Reference: 2009-May; vol 28 (issue 10) : pp 1445-63

Dates: Created 2009/04/13; Completed 2009/07/01; Revised 2009/07/17;

PMID: 19266565, status: MEDLINE (last retrieval date: 7/25/2009, IMS Date: )

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