Likelihood Based Study Designs for Time-to-Event Endpoints

Jeffrey D Blume; Leena Choi

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arXiv · 1711.01527

Likelihood Based Study Designs for Time-to-Event Endpoints

Jeffrey D Blume·Leena Choi

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Abstract

Likelihood methods for measuring statistical evidence obey the likelihood principle while maintaining bounded and well-controlled frequency properties. These methods lend themselves to sequential study designs because they measure the strength of statistical evidence in accumulating data without needing adjustments for the number of planned or unplanned examinations of data. However, sample size projections have, to date, only been developed for fixed sample size designs. In this paper, we consider sequential study designs for time-to-event outcomes assuming likelihood methods will be used to monitor the strength of statistical evidence for efficacy and futility. We develop sample size projections with the aim of controlling the probability of observing misleading evidence under the null and alternative hypotheses, and we show how efficacy and futility considerations are managed in this context. We also consider relaxing the requirement of specifying the simple alternative hypothesis in advance of the study. Finally, we end with a comparative illustration of these methods in a phase II cancer clinical trial that previously was designed within a Bayesian framework.

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Jeffrey D Blume, Leena Choi. 2017-11-05. Likelihood Based Study Designs for Time-to-Event Endpoints. https://arxiv.org/abs/1711.01527

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