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Activity Number:
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295
- Adaptive Designs and Interim Analyses
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Type:
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Contributed
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Date/Time:
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Tuesday, August 1, 2017 : 8:30 AM to 10:20 AM
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Sponsor:
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Biopharmaceutical Section
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Abstract #322641
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Title:
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A Two-Stage Design for Phase III Trials with Population Selection
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Author(s):
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Wen Li*
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Companies:
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Merck & Co. Inc.
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Keywords:
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bias ;
biomarker ;
interim analysis ;
subpopulation ;
time-to-event
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Abstract:
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A personalized medicine may benefit a subpopulation with certain predictive biomarker signatures or certain disease types and it is logical to take a two-stage approach with the study unless credible external information is available for decision making purpose. An interest of such study designs is the statistical property of the test-statistics and point estimate at the final analysis. Previous research has focused on type I error control and power calculation for such two-stage designs. This manuscript will investigate estimation bias of the treatment effect, which is implicit in the adjustment of nominal type I error for multiplicity control in such two-stage designs. This manuscript handles the treatment effect of an intermediate endpoint as a nuisance parameter to explore the bias and focuses on one previously studied design. In this design, patients with different biomarker levels are enrolled in a study and the treatment effect is assumed to be in an order. Closed form equations are provided for the estimation bias as well as the variance under the two designs. Simulations are conducted under various scenarios to validate the analytic results. Worked examples are presented.
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Authors who are presenting talks have a * after their name.
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