White Paper: Rechanneling the Cardiac Proarrhythmia Safety Paradigm

(Am Heart J 2014;0:1-9.)

 This white paper provides a summary of a scientific proposal presented at a Cardiac Safety Research Consortium/Health andEnvironmental Sciences Institute/Food and Drug Administration–sponsored Think Tank, held at Food and DrugAdministration's White Oak facilities, Silver Spring, MD, on July 23, 2013, with the intention of moving toward consensuson defining a new paradigm in the field of cardiac safety in which proarrhythmic risk would be primarily assessed usingnonclinical in vitro human models based on solid mechanistic considerations of torsades de pointes proarrhythmia. Thisnew paradigm would shift the emphasis from the present approach that strongly relies on QTc prolongation (a surrogatemarker of proarrhythmia) and could obviate the clinical Thorough QT study during later drug development. These discussionsrepresent current thinking and suggestions for furthering our knowledge and understanding of the public health case foradopting a new, integrated nonclinical in vitro/in silico paradigm, the Comprehensive In Vitro Proarrhythmia Assay, for theassessment of a candidate drug's proarrhythmic liability, and for developing a public-private collaborative programto characterize the data content, quality, and approaches required to assess proarrhythmic risk in the absence of a ThoroughQT study. This paper seeks to encourage multistakeholder input regarding this initiative and does not represent regulatoryguidance. 

To view the full PDF, please visit: http://www.safetypharmacology.org/Rechanneling_CardiacProarrhythmia.pdf


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