Pharmacometric Methods for Assessing Drug-Induced QT and QTc Prolongations for Non-Antiarrhythmic Drugs

Pharmacometrics: The Science of Quantitative Pharmacology

Volumn , Issue , 2006, Pages 977-992

  Sun, He ^a  

^a SunTech Research Institute   (United States)

Author keywords

QTc; QTc; Bazett corrected QT interval (QTcB); Electrocardiogram (ECG); Fridericia corrected QT interval (QTcF); Generate population corrected QTc data (QTcP); Heart rate; Heart rate corrected QT (QTc); Maximum mean change; Mean maximum change; Non antiarrhythmic drugs; Outliers; Proarrhythmic potential; QT interval; QT prolongation; Replicated ECGs; Sample size; Study designs; Subject specific corrected or individual corrected QTc (QTcI); Thorough QT (TQT) study; Torsades de pointes (TdP); TQT study

Indexed keywords

EID: 35248888736     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470087978.ch40     Document Type: Chapter

References (15)

1. S. G. Prior, Risk stratification in long QT syndrome. N Engl J Med 348:1866-1874 (2003).
2. QT/QTc Prolongation: Report from the PhRMA Statistics Expert Team, 14 August 2003, Investigating drug-induced QT and QTc prolongation in the clinic: statistical design and analysis considerations. Drug Inf J 39:243-266 (2003).
3. H. C. Bazett, An analysis of time relations of electrocardiograms. Heart 7:353-367 (1920).
4. L. S. Fridericia, Die Systolendauer im Elecktrokardiogramm bei normalen Menschen und bei Herzkranken. Ada Med Scand 53:469-486 (1920).
5. M. Malik, Problems of heart rate correction in the assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 12:411-420 (2001).
6. C. Funck-Brentano and P. Jaillon, Rate-corrected QT interval: techniques and limitations. Am J Cardiol 72:17B-22B (1993).
7. International Conference on Harmonisation (ICH) E14, Guidance for Industry, E9 Statistical Principles for Clinical Trials. www.fda.gov/cder/guidance/ (1998).
8. M. Malik and A. J. Camm, Evaluation of drug-induced QT interval prolongation. Drug Saf 24:323-351 (2001).
9. H. Sun, P. Chen, L. Kenna, and P. Lee, The chaotic QT interval variabilities on risk assessment trial designs. Clin Pharmacol Ther 75(2):P55 (2004).
10. H. Sun, P. Chen, J. Hunt, and H. Malinowski, Frequency of QT recording and the reliability of QT prolongation assessments. Clin Pharmacol Ther 75(2):P48 (2004).
11. M. Agin, D. Kazierad, R. Abel, R. Anziano, W. Billing, G. Layton, J. Mancuso, D. Stricter, W. Xu, R. Blum, and D. Jorkasky, Assessing QT variability in healthy volunteers. Presented at ACCP Annual Meeting, September 2003.
12. S. H. Lee, H. Sun, P. Chen, S. Doddapaneni, J. Hunt, and H. Malinowski, Sensitivity/reliability of the time-matched baseline subtraction method in assessment of QTc interval prolongation. Clin Pharmacol Ther 75(2):P56 (2004).
13. L. A. Kenna, A. Parekh, V. Jarugula, D. J. Chatterjee, H. Sun, M. J. Kim, S. Ortiz, J. P. Hunt, and H. Malinowski, Experience evaluating QT prolongation data. Clin Pharmacol Ther 75(2):P7 (2004)
14. C. Chuang-Stein, Safety analysis in controlled clinical trials. Drug Inf J 32:1363S-1372S (1998).
15. Quantitative Tools for Electrocardiogram Computation Harmonization (QTech), FDA, OCPB, Rockville, MD, 2004.