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Cardiac Safety Research Consortium: can the thorough QT/QTc study be replaced by early QT assessment in routine clinical pharmacology studies? Scientific update and a research proposal for a path forward.
- Source :
-
American heart journal [Am Heart J] 2014 Sep; Vol. 168 (3), pp. 262-72. Date of Electronic Publication: 2014 Jun 06. - Publication Year :
- 2014
-
Abstract
- The International Conference on Harmonization E14 guidance for the clinical evaluation of QT/QTc interval prolongation requires almost all new drugs to undergo a dedicated clinical study, primarily in healthy volunteers, the so-called TQT study. Since 2005, when the E14 guidance was implemented in United States and Europe, close to 400 TQT studies have been conducted. In February 2012, the Cardiac Safety Research Consortium held a think tank meeting at Food and Drug Administration's White Oak campus to discuss whether "QT assessment" can be performed as part of routine phase 1 studies. Based on these discussions, a group of experts convened to discuss how to improve the confidence in QT data from early clinical studies, for example, the First-Time-in-Human trial, through collection of serial electrocardiograms and pharmacokinetic samples and the use of exposure response analysis. Recommendations are given on how to design such "early electrocardiogram assessment," and the limitation of not having a pharmacologic-positive control in these studies is discussed. A research path is identified toward collecting evidence to replace or provide an alternative to the dedicated TQT study.<br /> (Copyright © 2014 Mosby, Inc. All rights reserved.)
- Subjects :
- Anti-Arrhythmia Agents pharmacokinetics
Anti-Arrhythmia Agents pharmacology
Arrhythmias, Cardiac chemically induced
Arrhythmias, Cardiac diagnosis
Drug Evaluation, Preclinical standards
Humans
Long QT Syndrome prevention & control
Patch-Clamp Techniques
Research Design
Anti-Arrhythmia Agents therapeutic use
Drug Evaluation, Preclinical methods
Electrocardiography
Heart Conduction System drug effects
Long QT Syndrome diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6744
- Volume :
- 168
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 25173536
- Full Text :
- https://doi.org/10.1016/j.ahj.2014.06.003