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Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials.

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.

SUBMITTER: Magirr D

PROVIDER: S-EPMC4749572 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials.

Magirr Dominic D Jaki Thomas T Koenig Franz F Posch Martin M

PloS one 20160210 2

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 ...[more]

PMID: 26863139

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