Universität zu Köln

Asikanius, Elina, Rufibach, Kaspar ORCID: 0000-0002-2634-1167, Bahlo, Jasmin, Bieska, Gabriele and Burger, Hans Ulrich (2016). Comparison of design strategies for a three-arm clinical trial with time-to-event endpoint: Power, time-to-analysis, and operational aspects. Biom. J., 58 (6). S. 1295 - 1311. HOBOKEN: WILEY-BLACKWELL. ISSN 1521-4036

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Abstract

To optimize resources, randomized clinical trials with multiple arms can be an attractive option to simultaneously test various treatment regimens in pharmaceutical drug development. The motivation for this work was the successful conduct and positive final outcome of a three-arm randomized clinical trial primarily assessing whether obinutuzumab plus chlorambucil in patients with chronic lympocytic lymphoma and coexisting conditions is superior to chlorambucil alone based on a time-to-event endpoint. The inference strategy of this trial was based on a closed testing procedure. We compare this strategy to three potential alternatives to run a three-arm clinical trial with a time-to-event endpoint. The primary goal is to quantify the differences between these strategies in terms of the time it takes until the first analysis and thus potential approval of a new drug, number of required events, and power. Operational aspects of implementing the various strategies are discussed. In conclusion, using a closed testing procedure results in the shortest time to the first analysis with a minimal loss in power. Therefore, closed testing procedures should be part of the statistician's standard clinical trials toolbox when planning multiarm clinical trials.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Asikanius, Elina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rufibach, Kaspar UNSPECIFIED orcid.org/0000-0002-2634-1167 UNSPECIFIED Bahlo, Jasmin UNSPECIFIED UNSPECIFIED UNSPECIFIED Bieska, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Burger, Hans Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-257059
DOI:	10.1002/bimj.201500077
Journal or Publication Title:	Biom. J.
Volume:	58
Number:	6
Page Range:	S. 1295 - 1311
Date:	2016
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1521-4036
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLOSED TESTING PROCEDURES; ADAPTIVE DESIGNS; PAIRWISE COMPARISONS; MULTIPLE ARMS; OBINUTUZUMAB; CHLORAMBUCIL; APPROVAL Multiple languages Mathematical & Computational Biology; Statistics & Probability Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25705