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Activity Number:
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220
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Type:
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Invited
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Date/Time:
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Tuesday, July 31, 2007 : 8:30 AM to 10:20 AM
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Sponsor:
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ENAR
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| Abstract - #307655 |
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Title:
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Two-Stage Designs for Dose-Finding Trials with a Biologic Endpoint Using Stepwise Tests
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Author(s):
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Mei-Yin C. Polley*+ and Ying-Kuen K. Cheung
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Companies:
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Amgen Inc. and Columbia University
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Address:
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2 Bayside Village Place, Suite # 301, San Francisco, CA, 94107,
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Keywords:
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Familywise error rate ; Futility interim ; Minimum effective dose ; Monotonicity ; Multiple comparison ; Probability of correct selection
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Abstract:
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We tackle the problem of early phase dose-finding trials with monotone biologic endpoints such as biologic measurements and laboratory values. A specific aim of this type of trial is to identify the minimum dose that exhibits adequate drug activity and shifts the mean of the endpoint from a zero doe, the so-called minimum effective dose. Stepwise tests for dose-finding have been well studied in the context of non-human studies where the sampling plan is done in one stage. We extend the notion of stepwise tests to a two-stage setting in an attempt to reduce the sample size requirement by shutting down unpromising doses in a futility interim. Specifically, we examine four two-stage designs and apply them to design a statin trial with four doses and a placebo in patients with Hodgkin's disease. We discuss the calibration of the design parameters and the implementation of these methods.
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