title: Recent developments in using mechanistic cardiac modelling for drug safety evaluation.
abstract: On the tenth anniversary of two key International Conference on Harmonisation (ICH) guidelines relating to cardiac proarrhythmic safety, an initiative aims to consider the implementation of a new paradigm that combines in vitro and in silico technologies to improve risk assessment. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative (co-sponsored by the Cardiac Safety Research Consortium, Health and Environmental Sciences Institute, Safety Pharmacology Society and FDA) is a bold and welcome step in using computational tools for regulatory decision making. This review compares and contrasts the state-of-the-art tools from empirical to mechanistic models of cardiac electrophysiology, and how they can and should be used in combination with experimental tests for compound decision making.
authors.affiliation: QT-Informatics, Macclesfield, UK. Electronic address: mark.davies@qtinformatics.com.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Davies
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Ken
authors.initials: K
authors.lastname: Wang
authors.affiliation: Computational Biology, Department of Computer Science, University of Oxford, OX1 3QD, UK.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Mirams
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Antonello
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Department of Physiology, Anatomy & Genetics, University of Oxford, OX1 3PT, UK.
authors.forename: Denis
authors.initials: D
authors.lastname: Noble
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Antje
authors.initials: A
authors.lastname: Walz
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lavé
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Franz
authors.initials: F
authors.lastname: Schuler
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Singer
authors.affiliation: Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Switzerland.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Polonchuk
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003657:Decision Making; D055808:Drug Discovery; D006321:Heart / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D018570:Risk Assessment