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General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy
Author(s) -
Li Zhihua,
Mirams Gary R.,
Yoshinaga Takashi,
Ridder Bradley J.,
Han Xiaomei,
Chen Janell E.,
Stockbridge Norman L.,
Wisialowski Todd A.,
Damiano Bruce,
Severi Stefano,
Morissette Pierre,
Kowey Peter R.,
Holbrook Mark,
Smith Godfrey,
Rasmusson Randall L.,
Liu Michael,
Song Zhen,
Qu Zhilin,
Leishman Derek J.,
SteidlNichols Jill,
Rodriguez Blanca,
BuenoOrovio Alfonso,
Zhou Xin,
Passini Elisa,
Edwards Andrew G.,
Morotti Stefano,
Ni Haibo,
Grandi Eleonora,
Clancy Colleen E.,
Vandenberg Jamie,
Hill Adam,
Nakamura Mikiko,
Singer Thomas,
Polonchuk Liudmila,
GreiterWilke Andrea,
Wang Ken,
Nave Stephane,
Fullerton Aaron,
Sobie Eric A.,
Paci Michelangelo,
Musuamba Tshinanu Flora,
Strauss David G.
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1647
Subject(s) - proarrhythmia , context (archaeology) , risk analysis (engineering) , session (web analytics) , computer science , medicine , pharmacology , biology , drug , paleontology , world wide web
This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration–sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate the progress in the development of a new cardiac safety paradigm, the Comprehensive in Vitro Proarrhythmia Assay (CiPA). The opinions regarding these principles reflect the collective views of those who participated in the discussion of this topic both at and after the breakout session. Although primarily discussed in the context of in silico models, these principles describe the interface between experimental input and model‐based interpretation and are intended to be general enough to be applied to other types of nonclinical models for proarrhythmia assessment. This document was developed with the intention of providing a foundation for more consistency and harmonization in developing and validating different models for proarrhythmia risk prediction using the example of the CiPA paradigm.