Highly automated QT measurement techniques in 7 thorough QT studies implemented under ICH E14 guidelines

  • Couderc J
  • Garnett C
  • Li M
 et al. 
  • 18


    Mendeley users who have this article in their library.
  • 27


    Citations of this article.


Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 +/- 24 ms on drug and 9.8 +/- 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 +/- 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 +/- 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods.

Author-supplied keywords

  • QT interval
  • drug cardiotoxicity
  • drug safety
  • electrocardiogram
  • moxifloxacin
  • thorough QT study

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Jean Philippe Couderc

  • Christine Garnett

  • Mike Li

  • Robert Handzel

  • Scott McNitt

  • Xiajuan Xia

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free