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Smaller sample sizes for phase II trials based on exact tests with actual error rates by trading-off their nominal levels of significance and power

Khan, I; Sarker, SJ; Hackshaw, AK; (2012) Smaller sample sizes for phase II trials based on exact tests with actual error rates by trading-off their nominal levels of significance and power. British Journal of Cancer , 107 1801 -1809. 10.1038/bjc.2012.444. Green open access

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Abstract

Background: Sample sizes for single-stage phase II clinical trials in the literature are often based on exact (binomial) tests with levels of significance (alpha (α) <5% and power >80%). This is because there is not always a sample size where α and power are exactly equal to 5% and 80%, respectively. Consequently, the opportunity to trade-off small amounts of α and power for savings in sample sizes may be lost. Methods: Sample-size tables are presented for single-stage phase II trials based on exact tests with actual levels of significance and power. Trade-off in small amounts of α and power allows the researcher to select from several possible designs with potentially smaller sample sizes compared with existing approaches. We provide SAS macro coding and an R function, which for a given treatment difference, allow researchers to examine all possible sample sizes for specified differences are provided. Results: In a single-arm study with P0 (standard treatment)=10% and P1 (new treatment)=20%, and specified α=5% and power=80%, the A’Hern approach yields n=78 (exact α=4.53%, power=80.81%). However, by relaxing α to 5.67% and power to 77.7%, a sample size of 65 can be used (a saving of 13 patients). Interpretation: The approach we describe is especially useful for trials in rare disorders, or for proof-of-concept studies, where it is important to minimise the trial duration and financial costs, particularly in single-arm cancer trials commonly associated with expensive treatment options.

Type: Article
Title: Smaller sample sizes for phase II trials based on exact tests with actual error rates by trading-off their nominal levels of significance and power
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/bjc.2012.444
Publisher version: http://dx.doi.org/10.1038/bjc.2012.444
Language: English
Additional information: This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Keywords: Sample size, Phase II design, Oncology, Exact tests, Simulation
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > UCL Medical School
URI: http://discovery.ucl.ac.uk/id/eprint/1400049
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