Assessing proarrhythmic potential of drugs when optimal studies are infeasible

Edwin P. Rock, John Finkle, Howard J. Fingert, Brian P. Booth, Christine E. Garnett, Stephen Grant, Robert L. Justice, Richard J. Kovacs, Peter R. Kowey, Ignacio Rodriguez, Wendy R. Sanhai, Colette Strnadova, Shari L. Targum, Yi Tsong, Kathleen Uhl, Norman Stockbridge

Research output: Contribution to journalReview article

63 Scopus citations

Abstract

Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed.

Original languageEnglish (US)
Pages (from-to)827-836.e1
JournalAmerican Heart Journal
Volume157
Issue number5
DOIs
StatePublished - May 2009

    Fingerprint

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Rock, E. P., Finkle, J., Fingert, H. J., Booth, B. P., Garnett, C. E., Grant, S., Justice, R. L., Kovacs, R. J., Kowey, P. R., Rodriguez, I., Sanhai, W. R., Strnadova, C., Targum, S. L., Tsong, Y., Uhl, K., & Stockbridge, N. (2009). Assessing proarrhythmic potential of drugs when optimal studies are infeasible. American Heart Journal, 157(5), 827-836.e1. https://doi.org/10.1016/j.ahj.2009.02.020