{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:03:56Z","timestamp":1785413036666,"version":"3.56.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Standardized care has become the cornerstone of modern medicine. However, many patients remain symptomatic despite following the appropriate guidelines and the application of treatment escalation, and become difficult-to-treat (D2T). The D2T concept can also provide a framework for identifying when standard care is no longer sufficient and when individualized management becomes clinically justified. Rather than reflecting therapeutic failure alone, the D2T state can be a consequence of various reasons, including underlying biological, clinical, psychosocial, or contextual complexity, which draws attention to the importance of multidomain reassessment in these conditions. Combined with emerging artificial intelligence-based trajectory recognition, the D2T framework may support earlier identification of complex patients and more selective implementation of precision strategies. In this way, the D2T concept can be understood as a practical bridge between standardized medicine and individualized care, with a potential relevance as a cross-disciplinary framework.<\/jats:p>","DOI":"10.3389\/fmed.2026.1918272","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:31Z","timestamp":1785409831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The road from standardized to personalized medicine: the difficult-to-treat framework as a critical waystation"],"prefix":"10.3389","volume":"13","author":[{"given":"Lilla","family":"Gunkl-T\u00f3th","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Semmelweis University","place":["Budapest, Hungary"]},{"name":"Department of Pharmacology and Pharmacotherapy, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]},{"name":"HUN-REN Chronic Pain Research Group","place":["P\u00e9cs, 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