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Activity Number:
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429
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Type:
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Contributed
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Date/Time:
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Wednesday, August 5, 2009 : 8:30 AM to 10:20 AM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #304395 |
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Title:
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A 'MiniPool' Approach for Combined Phase IIB/III Trial in Patients with Life-Threatening Disease
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Author(s):
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Y.H. Joshua Chen*+ and Keaven Anderson
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Companies:
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Merck Research Laboratories and Merck & Co., Inc.
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Address:
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P.O. Box 1000, North Wales, PA, 19454,
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Keywords:
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Phase IIB/III ; closed testing principle ; MiniPool ; HIV/AIDS ; Oncology
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Abstract:
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For life-threatening diseases (HIV/AIDS, oncology, etc.), doses studied in Phase IIB are usually chosen to be high enough to achieve a required therapeutic effect. These doses are likely located at or close to the plateau of a dose-response curve and have similar efficacy. We consider a combined Phase IIB/III design with multiple doses being tested in the Phase IIB portion and one selected for Phase III. A MiniPool (MINImum of possible POOLed statistics) method is proposed to test the hypothesis. Intuitively, the MiniPool statistic includes data from less efficacious doses and excludes toxic doses. The MiniPool method may be considered as an application of the closed testing principle. A clinical trial in HIV-infected patients is used to illustrate the method. A simulation study shows the MiniPool method controls type I error rate and preserves power compared to the naïve approach.
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