A HESI consortium approach to assess the human predictive value of non-clinical repolarization assays

Drug-induced ventricular arrhythmia and Torsades de Pointes remain a serious public health issues in bringing safe new pharmaceuticals to the market place. Under the auspices of the International Life Science Institute (ILSI)–Health and Environmental Sciences Institute (HESI), a consortium involving...

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Veröffentlicht in:Journal of pharmacological and toxicological methods 2009-07, Vol.60 (1), p.45-50
Hauptverfasser: Trepakova, Elena S., Koerner, John, Pettit, Syril D., Valentin, Jean-Pierre
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container_issue 1
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container_title Journal of pharmacological and toxicological methods
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creator Trepakova, Elena S.
Koerner, John
Pettit, Syril D.
Valentin, Jean-Pierre
description Drug-induced ventricular arrhythmia and Torsades de Pointes remain a serious public health issues in bringing safe new pharmaceuticals to the market place. Under the auspices of the International Life Science Institute (ILSI)–Health and Environmental Sciences Institute (HESI), a consortium involving representatives from pharmaceutical companies, regulatory agencies and opinion leaders from the scientific and medical research communities has been initiated. The objectives are (1) to assess the concordance between signals in non-clinical repolarization assays and clinical QT interval prolongation; (2) to investigate the mechanisms for any discrepancy identified between non-clinical and clinical results and to determine viable and successful alternative approaches to identify these compounds; and (3) to assess the proarrhythmic potential of such compounds. At present, the consortium is conducting a retrospective analysis of non-clinical and clinical data from both FDA and contributing companies' databases and supplementing with a literature review. The overall objectives of these initial efforts are to establish a quantitative integrated risk assessment for each compound; to define criteria for concordance and apply them to the database in order to identify non-concordant compounds.
doi_str_mv 10.1016/j.vascn.2009.05.002
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subjects Action Potentials
Animal models
Animals
Arrhythmias, Cardiac - chemically induced
Arrhythmias, Cardiac - physiopathology
Cardiac repolarization
Cardiac safety
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical - methods
Drug-Related Side Effects and Adverse Reactions
Electrocardiography
Guidelines as Topic
Humans
ILSI/HESI
Long QT Syndrome - chemically induced
Long QT Syndrome - physiopathology
Pro-Arrhythmia Models Project Committee
Program Development
QTc
Torsades de Pointes - chemically induced
Torsades de Pointes - physiopathology
title A HESI consortium approach to assess the human predictive value of non-clinical repolarization assays
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