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Updated: Jun 25, 2026

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Revisiting the Epistemological Foundations of Evidence-Based Medicine
Leonardo Y Kasputis Zanini1, Rafael Leite Pacheco1,2,3, Fábio Bertato4
1Department of Surgery, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo-SP, Brazil.
Objectives:
Evidence-based medicine (EBM) is frequently characterized as a purely empiricist enterprise. Previous discussions explicitly excluded rationalism from the epistemological analysis of EBM, restricting the discussion to empiricist frameworks. This article argues that such exclusion is untenable and that EBM is better understood as an integrated epistemic system in which empiricist and rationalist dimensions are interdependent and inseparable.
Methods:
A commentary with critical epistemological analysis of EBM, drawing on post-Kantian philosophy of science, to examine the rational structures embedded within EBM's methodology and clinical application.
Results:
EBM possesses a clear empiricist dimension in its reliance on systematic observation, controlled experimentation, and measurable outcomes. However, core elements of EBM such as the hierarchy of evidence, risk-of-bias assessment criteria, the inferential architecture of meta-analysis, and the translation of population-level estimates into individual clinical decisions are rational constructs that precede and organize empirical observation rather than emerging from it. Clinical expertise, integral to Sackett's canonical definition of EBM, operates primarily as a rational faculty. The empiricism-rationalism dichotomy was shown to be fundamentally inadequate, once that all knowledge arises from the interaction between sensory input and conceptual categories.
Conclusion:
Characterizing EBM as an exclusive applied empiricism is a philosophical misreading. EBM functions as an integrated epistemic system whose strength lies in the disciplined combination of experience and reason. Recognizing this complex nature provides conceptual tools to better understand both the achievements and the limitations of EBM in clinical practice.
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