Comparing Methods of Measurement for Detecting Drug‐Induced Changes in the QT Interval: Implications for Thoroughly Conducted ECG Studies

Abstract

This study demonstrated significant differences among four commonly used methods for QT interval measurement after pharmacological prolongation of cardiac repolarization. Observed large differences in variability of measurements will have a substantial impact on the sample size required to detect QT prolongation in the range that is currently advised in regulatory guidance.

Assessment of the 12-Lead ECG as a Screening Test for Detection of Cardiovascular Disease in Healthy General Populations of Young People (12–25 Years of Age)

“…192,208 Another source of variability in assessment of the ECG involves standardization of interval durations, which have changed with newer technology. 192,211 Evolution of these measurements in the era of digital electrocardiography has altered observed QT intervals (and QRS durations) from the established normal limits that were derived from single-channel (lead) recordings. Difficulty in measuring the QT interval with precision has obvious relevance to the reliable identification of LQTS as part of mass population screening ECGs.…”

The Future of Cardiac Safety Studies

“…In addition, there is poor link between the experimental model of QT c and clinical events. Many times, it's difficult to establish link between different episodes reported during study [1,[5][6][7].…”

Recommendations for the Standardization and Interpretation of the Electrocardiogram

“…The importance of this phenomenon is seen in determination of the QT interval, where different approaches to definition of T-wave offset can confound reproducibility. 58,59 It is in this context that differences in ECG measurement performance of different computer-assisted analysis programs must be placed. 15,17 …”

“…This is due in part to differences in the currently available algorithms that are used to define and to identify the end of the T wave, which can affect measurements. 59 Until reproducible methodology is established in this area, comparative analyses of ECGs must recognize the potential effect of different algorithms on resulting simultaneous lead measurements. Special situations, such as QT monitoring in drug trials, may continue to require alternative methods of QT measurement from single or multiple leads.…”

“…The importance of this phenomenon is seen in determination of the QT interval, where different approaches to definition of T-wave offset can confound reproducibility. 58,59 It is in this context that differences in ECG measurement performance of different computer-assisted analysis programs must be placed. 15,17 Clinical Implications The capability for simultaneous 12-lead data acquisition by modern digital electrocardiographs obligates major reconsideration of measurement standards and reference values for intervals that were originally derived from analog, singlechannel recordings.…”