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

INTRODUCTION: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.