Man versus Machine: Comparison of Automated and Manual Methodologies for Measuring the QTc Interval: A Prospective Study
Abstract
BACKGROUND: Electrocardiographic (ECG) safety evaluation is a required element of drug development. Performance characteristics of ECG measurement methodologies have rarely been studied prospectively.
METHODS: We conducted a randomized, placebo-controlled, crossover study in 24 subjects to evaluate effects of moxifloxacin on the Fridericia rate-corrected QT (QTcF) interval. Five ECG replicates were obtained at 30 time points. Change from baseline QTcF (ΔQTcF) was fit by mixed-model analysis of variance to evaluate residual standard deviation. Precision was defined as intrasubject QTcF variance. Two core lab approaches were compared: QTinno, fully automated, 5 replicates and HeartSignals, computer-assisted manual, 3 replicates. Core lab values were then compared to an automated commercial algorithm (VERITAS).
RESULTS: Twenty-three subjects provided 3450 ECGs potentially available for analysis. QTinno QTcF values were based upon 3419 ECGs, HeartSignals data on 2028 ECGs. Variance was similar between the QTinno and HeartSignals approaches (41.5 and 44 ms(2)). After excluding VERITAS QTcF measurements that deviated by >40 ms on visual review, variance in a set of 1907 common ECGs was lowest for HeartSignal, followed by QTinno and VERITAS (43.8, 52.6, 89.4 ms(2)) P = 0.02 HeartSignals versus QTinno, P < 0.0001 for both HeartSignals and QTinno versus VERITAS.
CONCLUSIONS: A fully automated core lab approach using 5 replicates and a computer-assisted manual approach using 3…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 24 participants or records.
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