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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 - #304127 |
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Title:
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Multiple Testing Issues of Prolongation Thorough QTc Clinical Trials
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Author(s):
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Yi Tsong and Jinglin Zhong*+ and Joanne Zhang
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Companies:
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FDA and FDA and FDA
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Address:
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10903 New Hampshire Ave, Silver Spring, MD, 20903,
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Keywords:
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QT/QTc ; Multiple testing ; non-inferiority
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Abstract:
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The ICH E14 defined that a negative thorough QT/QTc study has the largest 95% one-sided upper confidence interval of the time-matched mean effect of the drug on the QTc interval below 10 ms. This leads to the requirement of showing non-inferiority of the test treatment to placebo at multiple time points. Conventionally, this requirement is carried out by testing multiple hypothesis at 5% type I error rate each. The multiple comparison nature of the test leads to the concerns of type I error rate adjustment. Boos et al (2007) showed that when the repeated measured responses follow a multivariate normal distribution with equal variance, the conventional test is conservatively biased. In this presentation, we will discuss and evaluate a few alternative approaches proposed in the last few years.
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