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  • adaptive_survival_24OCT15

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  • journal.pone.0146465

    Rights statement: © 2016 Magirr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Sample size reassessment and hypothesis testing in adaptive survival trials

Research output: Contribution to journalJournal article

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Article numbere0146465
<mark>Journal publication date</mark>10/02/2016
<mark>Journal</mark>PLoS ONE
Issue number2
Volume11
Number of pages14
Publication StatusPublished
<mark>Original language</mark>English

Abstract

Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to-event endpoints is not easily handled by the standard theory. We analyze current methods that allow design modifications to be based on the full interim data, i.e., not only the observed event times but also secondary endpoint and safety data from patients who are yet to have an event. We show that the final test statistic may ignore a substantial subset of the observed event times. An alternative test incorporating all event times is
found, where a conservative assumption must be made in order to guarantee type I error control. We examine the power of this approach using the example of a clinical trial comparing two cancer therapies.