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General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy

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.; Steidl‐Nichols, Jill; Rodriguez, Blanca; Bueno‐Orovio, 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; Greiter‐Wilke, Andrea; Wang, Ken; Nave, Stephane; Fullerton, Aaron; Sobie, Eric A.; Paci, Michelangelo; Musuamba Tshinanu, Flora; Strauss, David G.

Authors

Zhihua Li

Takashi Yoshinaga

Bradley J. Ridder

Xiaomei Han

Janell E. Chen

Norman L. Stockbridge

Todd A. Wisialowski

Bruce Damiano

Stefano Severi

Pierre Morissette

Peter R. Kowey

Mark Holbrook

Godfrey Smith

Randall L. Rasmusson

Michael Liu

Zhen Song

Zhilin Qu

Derek J. Leishman

Jill Steidl‐Nichols

Blanca Rodriguez

Alfonso Bueno‐Orovio

Xin Zhou

Elisa Passini

Andrew G. Edwards

Stefano Morotti

Haibo Ni

Eleonora Grandi

Colleen E. Clancy

Jamie Vandenberg

Adam Hill

Mikiko Nakamura

Thomas Singer

Liudmila Polonchuk

Andrea Greiter‐Wilke

Ken Wang

Stephane Nave

Aaron Fullerton

Eric A. Sobie

Michelangelo Paci

Flora Musuamba Tshinanu

David G. Strauss



Abstract

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.

Journal Article Type Article
Publication Date 2020-01
Journal Clinical Pharmacology & Therapeutics
Print ISSN 0009-9236
Electronic ISSN 1532-6535
Publisher American Society for Clinical Pharmacology and Therapeutics
Peer Reviewed Peer Reviewed
Volume 107
Issue 1
Pages 102-111
APA6 Citation Li, Z., Mirams, G. R., Yoshinaga, T., Ridder, B. J., Han, X., Chen, J. E., …Strauss, D. G. (2020). General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy. Clinical Pharmacology and Therapeutics, 107(1), 102-111. https://doi.org/10.1002/cpt.1647
DOI https://doi.org/10.1002/cpt.1647
Keywords Pharmacology
Publisher URL https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.1647
Additional Information Received: 2019-06-24; Accepted: 2019-09-06; Published: 2019-11-10

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