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Activity Number:
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384
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Type:
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Topic Contributed
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Date/Time:
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Wednesday, August 6, 2008 : 10:30 AM to 12:20 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #301512 |
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Title:
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Statistical Issues of QT Prolongation Assessment Based on Linear Concentration Modeling
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Author(s):
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Yi Tsong*+ and Meiyu Shen and Zhong Jinglin and Joanne Zhang
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Companies:
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U.S. Food and Drug Administration and U.S. Food and Drug Administration and U.S. Food and Drug Administration and U.S. Food and Drug Administration
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Address:
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CDER, 5244 10903 New Hampshire Ave, Silver Spring, MD, 20993,
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Keywords:
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ICH ; Thorough QTc ; Concentration-response ; Linear model ; Intersection-union test
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Abstract:
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The ICH E14, 2005 defined that drug-induced prolongation of QT interval as evidenced by an upper bound of the 95% confidence interval around the mean effect on QTc of 10 ms or higher. This objective leads to the application of intersection-union test by testing the mean difference between the treatment and placebo of QTc change from baseline at each of the matched time point at which the observations are collected. The multiple comparison requirement nature of the intersection-union test leads to the concern of study efficiency. Based on the concept of clinical pharmacology, a concentration-response modeling approach was often adopted to assess the prolongation size of QTc interval induced by drug without carefully examine the validity of the assumptions involved. In most of the applications, the model is assumed to be either linear, log-linear or logistic.
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