Abstract
Drug-induced QT interval prolongation and Torsades de Pointes (TdP) remain serious public health issues in bringing safe new pharmaceuticals to the market place. To help address this issue, the ILSI Health and Environmental Sciences Institute (HESI), a consortium including representatives from pharmaceutical companies, regulatory agencies and opinion leaders from the scientific and medical research communities conducted a multi-year program to evaluate the predictivity of data submitted to the U.S. Food and Drug Administration (FDA). The project involved evaluation of data extracted from thorough clinical QT studies and non-clinical studies (i.e., in vitro hERG assay, action potential duration in isolated cardiac tissue, and in vivo QTc studies) submitted to the FDA to support marketing approval of new pharmaceuticals (150 drugs in the database). The data were evaluated for concordance between non-clinical repolarization assays and clinical measures of QT interval prolongation and established the sensitivity, specificity and predictivity of non-clinical assays towards clinical outcome. This introductory presentation will describe the program structure, participants, and objectives.
