Publications (2)3.99 Total impact
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Article: Effect of number of replicate electrocardiograms recorded at each time point in a thorough QT study on sample size and study cost.
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ABSTRACT: In a "thorough QT/QTc" (TQT) study, several replicate electrocardiograms (ECGs) are recorded at each time point to reduce within-subject variability. This decreases the sample size but increases the cost of ECG analysis. To determine the most cost-effective number of ECG replicates, the authors retrospectively analyzed data from the placebo and moxifloxacin arms of a TQT study with crossover design. Six replicate ECGs were recorded at 7 time points on day -1 (baseline day), day 1, and day 3 in 124 normal healthy volunteers who were randomized to receive moxifloxacin or placebo on day 1 and the other treatment on day 3. QT interval was corrected for heart rate by the Fridericia (QTcF) and individual subject-specific (QTcI) formulas. Within-subject and between-subject standard deviations for QTcF obtained by repeated-measures analysis of covariance were 9.5 and 13.3 milliseconds with 1 replicate; 7.8 and 12.7 milliseconds with 2 replicates; 7.3 and 12.3 milliseconds with 3 replicates; 6.9 and 12.2 milliseconds with 4 replicates; 6.8 and 11.9 milliseconds with 5 replicates; and 6.6 and 11.8 milliseconds with 6 replicates. Within- and between-subject variance with QTcI also declined with increasing replicates. Sample size benefit based on these estimates was negligible beyond 4 replicates. The study cost was least with 3 or 4 replicates, depending on per-ECG and per-subject costs.The Journal of Clinical Pharmacology 06/2011; 51(6):908-14. · 2.91 Impact Factor -
Article: Comparison of 5 methods of QT interval measurements on electrocardiograms from a thorough QT/QTc study: effect on assay sensitivity and categorical outliers.
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ABSTRACT: 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. 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. 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. The method of QT measurement must be considered when interpreting individual thorough QT/QTc studies.Journal of electrocardiology 01/2011; 44(2):96-104. · 1.08 Impact Factor
