title: Confirmatory adaptive designs with Bayesian decision tools for a targeted therapy in oncology.
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.
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Brannath
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zuber
authors.forename: Michael
authors.initials: M
authors.lastname: Branson
authors.forename: Frank
authors.initials: F
authors.lastname: Bretz
authors.forename: Paul
authors.initials: P
authors.lastname: Gallo
authors.forename: Martin
authors.initials: M
authors.lastname: Posch
authors.forename: Amy
authors.initials: A
authors.lastname: Racine-Poon
mesh_terms: D001499:Bayes Theorem; D001699:Biometry / Q000379:methods; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003661:Decision Support Techniques; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D009369:Neoplasms / Q000628:therapy*; D018579:Patient Selection