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Activity Number:
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341
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Type:
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Contributed
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Date/Time:
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Tuesday, August 8, 2006 : 2:00 PM to 3:50 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #306836 |
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Title:
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Bias in Estimates of QTc Prolongation by Timepoint-Wise Treatment Comparison
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Author(s):
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Yibin Wang*+ and Guohua Pan
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Companies:
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Novartis Pharmaceuticals Corporation and Johnson & Johnson Pharmaceutical R&D
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Address:
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One Health Plaza, East Hanover, NJ, 07936,
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Keywords:
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QT/QTC interval ; bias ; ICH E14 ; QT prolongation ; primary endpoint
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Abstract:
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Recent step 4 E14 guidance proposed the primary end point for QTc assessment as the change from baseline in QTc interval at timepoint corresponding to the maximum increase in subject-averaged QTc interval compared with placebo. The choice of the primary end point assumes that the time of maximum increase occurs at the same timepoint for all subjects, and coincides with the maximum effect of the treatment. Use of the above primary end point may result in underestimation of drug effect on QTc prolongation because of variation of the tmax. On the other hand, selection of the timepoint may lead to upwards bias in estimates of treatment effect by random noise that contributes high on-drug values or low placebo values. This study examines and quantifies the potential bias in estimates of QTc prolongation based on the primary end point under different exposure-QTc-response relationships.
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