Point estimation and p-values in phase II adaptive two-stage designs with a binary endpoint

• Verfasst von: Kunzmann, Kevin [VerfasserIn]
• Verfasst von: Kieser, Meinhard [VerfasserIn]
• Titel: Point estimation and p-values in phase II adaptive two-stage designs with a binary endpoint
• Verf.angabe: K. Kunzmann and M. Kieser
• E-Jahr: 2017
• Jahr: 15 March 2017
• Umfang: 14 S.
• Fussnoten: First published: 27 December 2016 ; Gesehen am 05.11.2018
• Titel Quelle: Enthalten in: Statistics in medicine
• Ort Quelle: Chichester [u.a.] : Wiley, 1982
• Jahr Quelle: 2017
• Band/Heft Quelle: 36(2017), 6, Seite 971-984
• ISSN Quelle: 1097-0258
• DOI: doi:10.1002/sim.7200
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adaptive design
• Sach-SW: oncology
• Sach-SW: optimal design
• Sach-SW: phase II
• Sach-SW: Simon's design
• K10plus-PPN: 1582568723

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.