Comparison of semiautomated and fully automated methods for QT measurement during a thorough QT/QTc study: variability and sample size considerations.
This study compares the ability of 2 semiautomated methods with a fully automated method for QT measurement to minimize the sample size required to detect a moxifloxacin effect and exclude a placebo effect in a thorough QT/QTc study. The fully automated and 1 of 2 semiautomated methods used a global QT measurement in 12 leads, whereas the other semiautomated method used a tangent method on single lead raw complexes. Mean QTcF intervals were greater when measured on a global QT electrocardiogram than on raw complexes, but the mean magnitudes of DeltaQTcF were similar for all methods. The 3 methods detected a statistically significant increase in QTcF for moxifloxacin compared to placebo and were able to exclude a placebo effect on QTcF in all 62 participants. However, due to a smaller variability, the semiautomated methods allowed these detections with fewer than 20 participants, whereas the fully automated required at least 27 participants.
Tyl
Benoît
B
MDS Pharma Services, Centralized Cardiac Services, 1-3, avenue du Bosquet, 95560 Baillet en France. benoit.tyl@mdsinc.com
Kabbaj
Meriam
M
Fassi
Basmah
B
De Jode
Patrick
P
Wheeler
William
W
D000328:Adult; D000368:Aged; D001372:Aza Compounds / Q000633:toxicity*; D018592:Cross-Over Studies; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory / Q000379:methods*; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000633:toxicity*; D018401:Sample Size; D012680:Sensitivity and Specificity; D055815:Young Adult
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin