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Activity Number:
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105
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Type:
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Contributed
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Date/Time:
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Monday, July 30, 2007 : 8:30 AM to 10:20 AM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #309659 |
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Title:
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A Hybrid of Traditional Design and Isotonic Regression Method To Find MTD in Phase I Cancer Clinical Trials
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Author(s):
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Robert Bigelow*+ and Chunpeng Fan and Richard Wu and Hui Quan
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Companies:
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sanofi-aventis and University of Wisconsin-Madison and sanofi-aventis and sanofi-aventis
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Address:
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9 Great Valley Parkway, Malvern, PA, 19355,
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Keywords:
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maximum tolerated dose ; continual reassessment method ; isotonic regression ; phase I study designs
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Abstract:
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Current methods for estimating Maximum Tolerated Dose (MTD) include the traditional 3+3 design (TD), an accelerated traditional design (TDacc), continual reassessment methods (CRM), and isotonic regression (IR). Each method has its own limitation. The proposed 'hybrid' methods first use TDacc to quickly approach the neighborhood of MTD and then switch to IR. They use only the monotone dose response assumption for toxicity, as with IR, and do not assume an explicit dose-toxicity model. Results from simulation studies demonstrate that these hybrid methods can perform better than the CRM methods when the true dose-toxicity model is unknown. They also need fewer patients compared to IR and produce more accurate estimates compared to TD. A numerical example is used to illustrate the application of the methods.
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