The road from standardized to personalized medicine: the difficult-to-treat framework as a critical waystation

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.