{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:32:11Z","timestamp":1781184731864,"version":"3.54.1"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Reliable and robust simulation of individual patients using patient-specific models (PSMs) is one of the next frontiers for modeling and simulation (M&amp;S) in healthcare. PSMs, which form the basis of digital twins, can be employed as clinical tools to, for example, assess disease state, predict response to therapy, or optimize therapy. They may also be used to construct virtual cohorts of patients, for <jats:italic>in silico<\/jats:italic> evaluation of medical product safety and\/or performance. Methods and frameworks have recently been proposed for evaluating the credibility of M&amp;S in healthcare applications. However, such efforts have generally been motivated by models of medical devices or generic patient models; how best to evaluate the credibility of PSMs has largely been unexplored. The aim of this paper is to understand and demonstrate the credibility assessment process for PSMs using patient-specific cardiac electrophysiological (EP) modeling as an exemplar. We first review approaches used to generate cardiac PSMs and consider how verification, validation, and uncertainty quantification (VVUQ) apply to cardiac PSMs. Next, we execute two simulation studies using a publicly available virtual cohort of 24 patient-specific ventricular models, the first a multi-patient verification study, the second investigating the impact of uncertainty in personalized and non-personalized inputs in a virtual cohort. We then use the findings from our analyses to identify how important characteristics of PSMs can be considered when assessing credibility with the approach of the ASME V&amp;V40 Standard, accounting for PSM concepts such as inter- and intra-user variability, multi-patient and \u201cevery-patient\u201d error estimation, uncertainty quantification in personalized vs non-personalized inputs, clinical validation, and others. The results of this paper will be useful to developers of cardiac and other medical image based PSMs, when assessing PSM credibility.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010541","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T17:29:01Z","timestamp":1665422941000},"page":"e1010541","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Credibility assessment of patient-specific computational modeling using patient-specific cardiac modeling as an exemplar"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-1838","authenticated-orcid":true,"given":"Suran","family":"Galappaththige","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline 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