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

Zhihua Li, Gary R. Mirams, 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-NicholsBlanca 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

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)102-111
Number of pages10
JournalClinical pharmacology and therapeutics
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Li, Z., Mirams, G. R., Yoshinaga, T., Ridder, B. J., Han, X., Chen, J. E., Stockbridge, N. L., Wisialowski, T. A., Damiano, B., Severi, S., Morissette, P., Kowey, P. R., Holbrook, M., Smith, G., Rasmusson, R. L., Liu, M., Song, Z., Qu, Z., Leishman, D. J., ... 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