Abstract:
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A prolonged QT interval in ECG measurements is indicative of an electrophysiological environment that promotes certain ventricular arrhythmias. Accordingly, every compound in clinical development must undergo a costly Thorough QT (TQT) study before regulatory submission. A concentration-response analysis is an alternative. In 2015 ICH E14 clarified the concentration-response analysis can serve as the primary basis for decisions to classify the risk of a drug. In this presentation, a concentration-response analysis was initially performed based on a non-TQT study. And re-performed after TQT data were available. The two analyses yield different conclusions which required further investigation. Bootstrap was used to compare several different scenarios. The results showed that the analysis using the non-TQT study could be improved significantly if additional ECG baselines were included in the design, specifically the ECG baselines should be measured at all of the time points where the ECGs would be measured after the drug administration. This result improves the study design, enhances the ECG data for non TQT studies, and has a strong positive impact on concentration-QTc analysis.
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