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Activity Number:
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463
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Type:
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Topic Contributed
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Date/Time:
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Wednesday, August 5, 2009 : 10:30 AM to 12:20 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #304126 |
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Title:
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Adaptive type I error rate spending approach for validation and non-inferiority tests of thorough QT studies
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Author(s):
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Yi Tsong*+ and Joanne Zhang
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Companies:
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FDA and FDA
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Address:
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CDER, 10903 New Hampshire Ave, Silver Spring, MD, 20993,
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Keywords:
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thorough QT study ; Non-inferiority test ; Validation test ; Type I error rate spending ; Adaptive design
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Abstract:
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The objective of a thorough QT clinical trial is to demonstrate that a test treatment will not induce prolongation of QT interval in healthy subjects. This is carried out by showing the maximum mean effect on QT interval adjusted by the time-matched placebo effect is less than 10 ms. On the other hand, in order to minimize the chance of false negative claim when the selected study subjects do not respond to treatment with known QT prolongation effect, the trial is designed with an active control treatment. The negative conclusion of QT prolongation induced by the test treatment is validated if it is demonstrated that the maximum QT prolongation effect induced by the positive control treatment after adjusted for the placebo effect at the matched time point is greater than 5 ms. In a group sequential design setting, we consider two alternative hierarchical testing designs. The first design
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