Sample size reassessment and hypothesis testing in adaptive survival trials

Magirr, Dominic and Jaki, Thomas Friedrich and Koenig, Franz and Posch, Martin (2016) Sample size reassessment and hypothesis testing in adaptive survival trials. PLoS ONE, 11 (2). ISSN 1932-6203

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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.

Item Type:
Journal Article
Journal or Publication Title:
PLoS ONE
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700
Subjects:
ID Code:
77532
Deposited By:
Deposited On:
07 Jan 2016 09:26
Refereed?:
Yes
Published?:
Published
Last Modified:
22 Oct 2020 03:15