Evidentiary challenges to evidence-based medicine
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Updated: Oct 13, 2026

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
B Djulbegovic1, L Morris, G H Lyman
1Department of Internal Medicine, H Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa 33612-9497, USA.
Abstract:
The evidence-based medicine (EBM) movement has exerted a strong influence on contemporary medicine. It has been used to define the hierarchy of knowledge in clinical medicine by classifying clinical findings according to the perceived relevance and validity of the respective methodologies of studies from which evidence was collected. In the spectrum of theories of knowledge, EBM predominantly relies on findings obtained from population-derived clinical research. This reliance on knowledge obtained from population studies sharply contrasts with a physiologic model of clinical knowledge advocated by basic science researchers and many clinicians. An apparent schism between proponents of physiologic and population models in the approach to the practice of medicine has been created. This dichotomy between practising physicians and EBM physicians in the approach to clinical knowledge should not be irreconcilable. We advocate a consilient approach to the interpretation of evidence and the integration of medical knowledge. This approach relies on 'linking of facts and fact-based theory across various disciplines to create a common groundwork of explanation'.
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