Comparison of 5 methods of QT interval measurements on electrocardiograms from a thorough QT/QTc study: effect on assay sensitivity and categorical outliers.
BACKGROUND
We studied moxifloxacin-induced QT prolongation and proportion of categorical QTc outliers when 5 methods of QT measurement were used to analyze electrocardiograms (ECGs) from a thorough QT study.


METHODS
QT interval was measured by the threshold, tangent, superimposed median beat, automated global median beat, and longest QT methods in a central ECG laboratory in 2730 digital ECGs from 39 subjects during placebo and moxifloxacin treatment.


RESULTS
All 5 methods were able to demonstrate statistically significant moxifloxacin-induced QTcF prolongation. However, lower bound of 95% 1-sided confidence interval of QTcF prolongation did not exceed 5 milliseconds with the longest QT method. More QTcF outliers were observed with the longest QT and tangent methods, whereas the other 3 methods were comparable. QTcF values greater than 500 milliseconds were observed only with moxifloxacin by the tangent method, and with moxifloxacin and placebo by the longest QT method.


CONCLUSIONS
The method of QT measurement must be considered when interpreting individual thorough QT/QTc studies.
Research Section, Quintiles Cardiac Safety Services, Mumbai, India. vaibhav.salvi@quintiles.com
Vaibhav
V
Salvi
Dilip R
DR
Karnad
Gopi Krishna
GK
Panicker
Mili
M
Natekar
Pooja
P
Hingorani
Vaibhav
V
Kerkar
Arumugam
A
Ramasamy
Michiel
M
de Vries
Troy
T
Zumbrunnen
Snehal
S
Kothari
Dhiraj
D
Narula
D000465:Algorithms; D000818:Animals; D016477:Artifacts; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D004562:Electrocardiography / Q000379:methods*; D006339:Heart Rate; D008133:Long QT Syndrome / Q000175:diagnosis*; D015588:Observer Variation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity