title: Point estimation and p-values in phase II adaptive two-stage designs with a binary endpoint.
abstract: Clinical trials in phase II of drug development are frequently conducted as single-arm two-stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non-informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Institute for Medical Biometry and Informatics, University of Heidelberg, Marsilius Arkaden, Im Neuenheimer Feld 130.3, Heidelberg, 69120, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kunzmann
authors.affiliation: Institute for Medical Biometry and Informatics, University of Heidelberg, Marsilius Arkaden, Im Neuenheimer Feld 130.3, Heidelberg, 69120, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kieser
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D006801:Humans; D015233:Models, Statistical; D018401:Sample Size
keywords: Simon's design; adaptive design; oncology; optimal design; phase II