1. Assessing proarrhythmic potential of drugs when optimal studies are infeasible.
- Author
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Rock EP, Finkle J, Fingert HJ, Booth BP, Garnett CE, Grant S, Justice RL, Kovacs RJ, Kowey PR, Rodriguez I, Sanhai WR, Strnadova C, Targum SL, Tsong Y, Uhl K, and Stockbridge N
- Subjects
- Animals, Controlled Clinical Trials as Topic methods, Drug Approval organization & administration, Drug Evaluation, Preclinical methods, Electrocardiography drug effects, Humans, International Cooperation, Long QT Syndrome physiopathology, Drugs, Investigational adverse effects, Long QT Syndrome chemically induced
- 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.
- Published
- 2009
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