White paper: Uncertainty and variability in computational and mathematical models of cardiac physiology.
Journal of Physiology
© 2016 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The Cardiac Physiome effort is one of the most mature and successful applications of mathematical and computational models for describing and advancing the understanding of physiology. After five decades of development, physiological cardiac models are poised to realise the promise of translational research via clinical applications such as drug development and patient specific approaches as well as ablation, cardiac resynchronisation, and contractility modulation therapies. For models to be included as a vital component of the decision process in safety critical applications, rigorous assessment of model credibility will be required. This White Paper describes one aspect of this process by identifying and classifying sources of variability and uncertainty in moels as well as their implications for the application and development of cardiac models. We stress the need to understand and quantify the sources of variability and uncertainty in model inputs, the impact of model structure and complexity, and their consequences for predictive model outputs. We propose that the future of the Cardiac Physiome should include a probabilistic approach to quantify the relationship of variability and uncertainty of model inputs and outputs. This article is protected by copyright. All rights reserved.
GRM gratefully acknowledges support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 101222/Z/13/Z). RHC gratefully acknowledges funding from the UK Engineering and Physical Sciences Research Council (Grant Numbers EP/K037145/1 and EP/L001101/1)
This is the final version of the article. Available from Wiley via the DOI in this record.
Available online 15th March 2016