Number of ECG Replicates Influences the Estimated QT Prolonging Effect of a Drug

Abstract

The present analysis addressed the effect of the number of ECG replicates extracted from a continuous ECG on estimated QT interval prolongation for different QT correction formulas.

For one hundred healthy volunteers, who received a compound prolonging the QT interval, 18 ECG replicates within a 3 minute window were extracted from 12-lead Holter ECGs. Ten QT correction formulas were deployed and the QTc interval was controlled for baseline and placebo and averaged per dose level.

The mean prolongation difference was >4 ms for single and > 2 ms for triplicate ECG measurements compared to the 18 ECG replicate mean value. The difference was <0.5ms after 14 replicates. In contrast, concentration-effect analysis was independent of replicate count and also of QT correction formula.

The number of ECG replicates impacted the estimated QT interval prolongation for all deployed QT correction formulas. However, concentration-effect analysis was independent of both the replicate number and correction formula. INTRODUCTION METHODS RESULTS CONCLUSION