Comparison of QTinno, a fully automated electrocardiographic analysis program, to semiautomated electrocardiographic analysis methods in a drug safety study in healthy subjects.
BACKGROUND
Improved automated methods for electrocardiographic (ECG) analysis are needed, particularly for drug development purposes.


OBJECTIVE
This study compared a novel fully automated method for ECG analysis (QTinno; NewCardio, Santa Clara, CA) to 2 semiautomated digital methods: global measurement from the earliest QRS onset to the latest T-wave offset on representative superimposed beats (global) and tangent measurement on 3 consecutive beats in one lead (tangent).


METHODS
All 3 methods were used to determine uncorrected and rate-corrected QT interval duration (QT and QTcF) and related metrics in 1422 digital 12-lead ECGs from a phase 1 drug study. Global and tangent annotations were manually adjusted by the same 3 cardiologists wherever necessary. No adjustments were made in QTinno determinations.


RESULTS
QTinno returned QTcF change from time-matched baseline (DeltaQTcF) that differed minimally from both global and tangent methods (mean pairwise difference: 0.1 millisecond between QTinno and global, 1.1 milliseconds between QTinno and tangent). The average absolute QT and QTcF intervals by QTinno were approximately 5 milliseconds longer than global and 25 milliseconds longer than by tangent. QTinno had lower intrinsic variability for DeltaQTcF than either global or tangent (between-subject SD: QTinno 4.0 milliseconds, global 5.6 milliseconds, tangent 6.4 milliseconds; within-subject SD: QTinno 4.8 milliseconds, global 7.4 milliseconds, tangent 10.6 milliseconds). All methods were robust in detecting the largest placebo-adjusted mean time-matched DeltaQTcF (15-25 milliseconds) induced by study drug.


CONCLUSIONS
The methods show good agreement for drug-induced QTc prolongation. Lower intrinsic variability of DeltaQTcF by QTinno could facilitate smaller sample sizes or increase study power in thorough QTc studies.
Sarapa
Nenad
N
Johnson & Johnson PRD, Spring House, PA, USA.
Gussak
Ihor
I
Vajdic
Branislav
B
George
Samuel
S
Hadzievski
Ljupco
L
Francom
Steven F
SF
Kowey
Peter
P
D000465:Algorithms; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D004341:Drug Evaluation / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000379:methods*; D006801:Humans; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software