The impact of experimental designs & system sloppiness on the personalisation process: A cardiovascular perspective

Harry Saxton, Daniel J Taylor, Grace Faulkner, Ian Halliday, Tom Newman, Torsten Schenkel, Paul D Morris, Richard H Clayton and Xu Xu

PLOS ONE, 2025, vol. 20, issue 6, 1-29

Abstract: To employ a reduced-order cardiovascular model as a digital twin for personalised medicine, it is essential to understand how uncertainties in the model’s input parameters affect its outputs. The aim is to identify a set of input parameters that can serve as clinical biomarkers, providing insight into a patient’s physiological state. Given the challenge of finding useful clinical data, careful consideration must be given to the experimental design used to acquire patient-specific input parameters. Model sloppiness—where numerous parameter combinations have minimal impact on model predictions, whilst only a few parameters significantly influence outcomes—is a critical concept in this context. In this paper, we conduct the first quantification of a cardiovascular system’s sloppiness to elucidate the structure of the input parameter space. By utilising Sobol indices and examining various synthetic cardiovascular measures with increasing invasiveness, we uncover how the personalisation process and the cardiovascular system’s sloppiness are contingent upon the chosen experimental design. Our findings reveal that continuous clinical measures induce system sloppiness and increase the number of personalisable biomarkers, whereas discrete clinical measurements produce a non-sloppy system with a reduced number of biomarkers. This study underscores the necessity for careful consideration of available clinical data as differing measurement sets can significantly impact model personalisation.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0326112

DOI: 10.1371/journal.pone.0326112

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