{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:51:36Z","timestamp":1792615896692,"version":"4.5.0"},"reference-count":33,"publisher":"JMIR Publications Inc.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JMIR Med Inform"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Therapeutic drug monitoring (TDM) aims to optimize clinical outcomes but is hindered by logistical delays and susceptibility to data errors. Integrating model-informed precision dosing with point-of-care testing, fortified by rule-based validation and alerts, forms a transformative clinical decision support system (CDSS) essential for securing this complex workflow.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n This study evaluates,\n in silico<\/jats:italic>\n , the effectiveness of a rule-based CDSS for imatinib in detecting data-quality issues and optimizing therapeutic dosing, compared with a human TDM expert.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We simulated a set of 60 virtual patients using a previously developed population pharmacokinetic model and deliberately enriched it with data-quality errors (eg, timing inaccuracies and reporting errors) to stress-test system resilience. We compared CDSS and TDM expert performances based on their error-detection capabilities and the clinical impact on therapeutic target attainment and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The CDSS and the expert demonstrated comparable error-detection capabilities. The CDSS showed numerically higher sensitivity (53%,\n \n 95% CI 35%\u201070% vs 45%, 95% CI 30%\u201061%) and lower specificity (83%, 95% CI 63%\u201095% vs 100%, 95% CI 81%\u2010100%). Clinically, the CDSS demonstrated significantly higher rates of target attainment than the expert (33\/60, 55% vs 22\/60, 37%;\n P<\/jats:italic>\n =.046). However, the CDSS resulted in 5 detrimental outcomes against 1 for the TDM expert, in which patients initially within the target range fell outside it.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The CDSS demonstrated high efficacy in optimizing imatinib exposure while serving as a robust digital gatekeeper. While active optimization drives higher efficacy, a few observed detrimental cases highlight that algorithmic safety remains contingent on data integrity. This proof-of-concept study validates the CDSS architecture as a prerequisite for future prospective clinical trials.<\/jats:p>\n <\/jats:sec>","DOI":"10.2196\/93304","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T13:30:05Z","timestamp":1787491805000},"page":"e93304-e93304","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Performance Evaluation of a Clinical Decision Support System for Imatinib Therapeutic Drug Monitoring: In Silico Study"],"prefix":"10.2196","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8426-6157","authenticated-orcid":false,"given":"Yuan James","family":"P\u00e9termann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7283-7203","authenticated-orcid":false,"given":"Roberto","family":"Rigamonti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-4277","authenticated-orcid":false,"given":"Paul","family":"Thoueille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1940-5807","authenticated-orcid":false,"given":"Junrui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0446-5337","authenticated-orcid":false,"given":"Lavinia","family":"Alberi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6592-3213","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Veuve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-4978","authenticated-orcid":false,"given":"Eva","family":"Choong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3230-7345","authenticated-orcid":false,"given":"Bruno","family":"Da Rocha Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0404-7917","authenticated-orcid":false,"given":"Sandro","family":"Carrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-927X","authenticated-orcid":false,"given":"Fran\u00e7ois R","family":"Girardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0639-5536","authenticated-orcid":false,"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-082X","authenticated-orcid":false,"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-6104","authenticated-orcid":false,"given":"Yann","family":"Thoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-9317","authenticated-orcid":false,"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1010","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00177","article-title":"The steps to therapeutic drug monitoring: a structured approach illustrated with imatinib","volume":"11","author":"Buclin","journal-title":"Front Pharmacol"},{"issue":"1","key":"R2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3904\/kjim.2009.24.1.1","article-title":"Overview of therapeutic drug monitoring","volume":"24","author":"Kang","journal-title":"Korean J Intern Med"},{"issue":"6","key":"R3","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlae182","article-title":"State of the art of real-life concentration monitoring of rifampicin and its implementation contextualized in resource-limited settings: the Tanzanian case","volume":"6","author":"Petermann","journal-title":"JAC Antimicrob Resist"},{"issue":"5","key":"R4","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1097\/FTD.0000000000000901","article-title":"Review of the preanalytical errors that impact therapeutic drug monitoring","volume":"43","author":"Peck Palmer","journal-title":"Ther Drug Monit"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115421","article-title":"Model-informed precision dosing: state of the art and future perspectives","volume":"215","author":"Minichmayr","journal-title":"Adv Drug Deliv Rev"},{"issue":"4","key":"R6","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15041283","article-title":"Precision oncology by point-of-care therapeutic drug monitoring and dosage adjustment of conventional cytotoxic chemotherapies: a perspective","volume":"15","author":"Briki","journal-title":"Pharmaceutics"},{"issue":"1","key":"R7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1097\/FTD.0000000000001384","article-title":"Therapeutic drug monitoring and point-of-care technologies: opportunities and current challenges","volume":"48","author":"Carrara","journal-title":"Ther Drug Monit"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosx.2025.100620","article-title":"Imatinib detection by memristive biosensors for therapeutic drug monitoring","volume":"24","author":"Chen","journal-title":"Biosens Bioelectron X"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-020-0221-y","article-title":"An overview of clinical decision support systems: benefits, risks, and strategies for success","volume":"3","author":"Sutton","journal-title":"NPJ Digit Med"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.15265\/IYS-2016-s034","article-title":"Clinical decision support: a 25 year retrospective and a 25 year vision","volume":"Suppl 1","author":"Middleton","journal-title":"Yearb Med Inform"},{"issue":"6","key":"R11","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1197\/jamia.M1370","article-title":"Ten commandments for effective clinical decision support: making the practice of evidence-based medicine a reality","volume":"10","author":"Bates","journal-title":"J Am Med Inform Assoc"},{"issue":"24","key":"R12","doi-asserted-by":"publisher","first-page":"5925","DOI":"10.1007\/s00216-020-02545-4","article-title":"Towards point of care systems for the therapeutic drug monitoring of imatinib","volume":"412","author":"Pearce","journal-title":"Anal Bioanal Chem"},{"issue":"10","key":"R13","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s40262-023-01293-9","article-title":"Therapeutic drug monitoring of kinase inhibitors in oncology","volume":"62","author":"van der Kleij","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"R14","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15041081","article-title":"From personalized to precision medicine in oncology: a model-based dosing approach to optimize achievement of imatinib target exposure","volume":"15","author":"Goutelle","journal-title":"Pharmaceutics"},{"issue":"23","key":"R15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.133.133","article-title":"Personalized daily doses of imatinib by therapeutic drug monitoring increase the rates of molecular responses in patients with chronic myeloid leukemia. Final results of the randomized OPTIM Imatinib study","volume":"126","author":"Rousselot","journal-title":"Blood"},{"issue":"8","key":"R16","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081676","article-title":"Imatinib optimized therapy improves major molecular response rates in patients with chronic myeloid leukemia","volume":"14","author":"Johnson-Ansah","journal-title":"Pharmaceutics"},{"issue":"8","key":"R17","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.18553\/jmcp.2021.27.8.1077","article-title":"The cost-effectiveness of therapeutic drug monitoring for the prescription drug-based treatment of chronic myeloid leukemia","volume":"27","author":"Conti","journal-title":"J Manag Care Spec Pharm"},{"issue":"9","key":"R18","doi-asserted-by":"publisher","first-page":"1994","DOI":"10.1111\/bcp.13990","article-title":"Optimizing the dose in patients treated with imatinib as first line treatment for gastrointestinal stromal tumours: a cost-effectiveness study","volume":"85","author":"Zuidema","journal-title":"Br J Clin Pharmacol"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.08.033","article-title":"Therapeutic drug monitoring in oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology consensus guidelines for imatinib therapy","volume":"157","author":"Clarke","journal-title":"Eur J Cancer"},{"issue":"11","key":"R20","doi-asserted-by":"publisher","first-page":"e854","DOI":"10.1016\/S2352-3026(22)00246-0","article-title":"The influence of drug prices, new availability of inexpensive generic imatinib, new approvals, and post-marketing research on the treatment of chronic myeloid leukaemia in the USA","volume":"9","author":"Kantarjian","journal-title":"Lancet Haematol"},{"key":"R21","unstructured":"Monolix documentation (versions 2024R1). Zenodo. 2024. URL: https:\/\/zenodo.org\/records\/14918014 [Accessed 25-09-2026]"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-026-01181-5","article-title":"Optimizing imatinib sampling strategies through a population approach: a crucial step to model-informed precision dosing validation for point-of-care therapeutic drug monitoring","author":"P\u00e9termann","journal-title":"BMC Pharmacol Toxicol"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.2196\/58720","article-title":"Toward a clinical decision support system for monitoring therapeutic antituberculosis medical drugs in Tanzania (Project TuberXpert): protocol for an algorithm\u2019 development and implementation","volume":"13","author":"Thoma","journal-title":"JMIR Res Protoc"},{"key":"R24","unstructured":"sotalya. GitHub. URL: https:\/\/github.com\/sotalya [Accessed 21-07-2026]"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/j.smhl.2025.100600","article-title":"Tucuxi-Core: an open source generic and efficient computing engine for model-informed precision dosing","volume":"38","author":"Thoma","journal-title":"Smart Health"},{"key":"R26","unstructured":"Thoma Y . Tucuxi-CDSS documentation. Tucuxi-CDSS. URL: https:\/\/tucuxi-cdss-core.readthedocs.io\/en\/latest\/ [Accessed 21-07-2026]"},{"key":"R27","doi-asserted-by":"crossref","unstructured":"Rigamonti R P\u00e9termann YJ Herzig M et al. A configurable clinical decision support system for model-informed precision dosing: system architecture and operational principles. JMIR Preprints. Preprint posted online on Mar 13, 2026. [doi: 10.2196\/preprints.95203]","DOI":"10.2196\/preprints.95203"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2017.00307","article-title":"Sensitivity, specificity, and predictive values: foundations, pliabilities, and pitfalls in research and practice","volume":"5","author":"Trevethan","journal-title":"Front Public Health"},{"issue":"4","key":"R29","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1093\/biomet\/26.4.404","article-title":"The use of confidence or fiducial limits illustrated in the case of the binomial","volume":"26","author":"Clopper","journal-title":"Biometrika"},{"issue":"2","key":"R30","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/BF02295996","article-title":"Note on the sampling error of the difference between correlated proportions or percentages","volume":"12","author":"McNemar","journal-title":"Psychometrika"},{"issue":"6","key":"R31","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1007\/s00280-014-2599-1","article-title":"Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: results from a randomized controlled trial","volume":"74","author":"Gotta","journal-title":"Cancer Chemother Pharmacol"},{"issue":"5","key":"R32","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1136\/amiajnl-2011-000612","article-title":"High-priority drug-drug interactions for use in electronic health records","volume":"19","author":"Phansalkar","journal-title":"J Am Med Inform Assoc"},{"issue":"3","key":"R33","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.jclinepi.2013.08.015","article-title":"Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects","volume":"67","author":"McCambridge","journal-title":"J Clin Epidemiol"}],"container-title":["JMIR Medical Informatics"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:13:38Z","timestamp":1792613618000},"score":1,"resource":{"primary":{"URL":"https:\/\/medinform.jmir.org\/2026\/1\/e93304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":33,"URL":"https:\/\/doi.org\/10.2196\/93304","relation":{},"ISSN":["2291-9694"],"issn-type":[{"value":"2291-9694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"article-number":"v14i1e93304"}}