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:
CreatorsEmailORCIDORCID Put Code
Asikanius, ElinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rufibach, KasparUNSPECIFIEDorcid.org/0000-0002-2634-1167UNSPECIFIED
Bahlo, JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bieska, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burger, Hans UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
CLOSED TESTING PROCEDURES; ADAPTIVE DESIGNS; PAIRWISE COMPARISONS; MULTIPLE ARMS; OBINUTUZUMAB; CHLORAMBUCIL; APPROVALMultiple languages
Mathematical & Computational Biology; Statistics & ProbabilityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25705

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