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Updated: Mar 25, 2026

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
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Engineering framework for curiosity-driven and humble AI in clinical decision support.

Janan Arslan1,2, Kurt Benke3, Sebastian Andres Cajas Ordones4

  • 1Institut du Cerveau, Sorbonne Universite, Paris, France.

BMJ Health & Care Informatics
|March 23, 2026
PubMed
Summary
This summary is machine-generated.

The BODHI framework enhances clinical AI by promoting curiosity and humility in large language models (LLMs). This AI engineering approach improves decision support quality and encourages necessary information gathering for safer deployment.

Keywords:
Artificial intelligenceBMJ Health InformaticsComputing MethodologiesConsumer health informaticsContinuity of Patient Care

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Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
05:47

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Area of Science:

  • Artificial Intelligence
  • Clinical Decision Support
  • Medical Informatics

Background:

  • Large language models (LLMs) in clinical AI often exhibit overconfidence, lacking genuine medical understanding.
  • This overconfidence stems from conflating statistical pattern recognition with true clinical reasoning.
  • There is a need for AI systems that demonstrate appropriate uncertainty and information-seeking behavior.

Purpose of the Study:

  • To introduce BODHI (Balanced, Open-minded, Diagnostic, Humble, and Inquisitive), an engineering framework for developing humble and curiosity-driven clinical AI.
  • To address the limitations of LLMs in expressing appropriate confidence and epistemic uncertainty.
  • To constrain LLM responses using virtue-based rules and uncertainty decomposition.

Main Methods:

  • Developed BODHI, a dual reflective architecture for AI systems.
  • Implemented uncertainty decomposition into task-specific dimensions.
  • Constrained model responses using virtue-based stance rules derived from a Virtue Activation Matrix.
  • Validated the framework on 200 clinical vignettes using GPT-4o-mini and GPT-4.1-mini.

Main Results:

  • BODHI significantly improved overall clinical response quality for both GPT-4.1-mini (+16.6 pp) and GPT-4o-mini (+2.2 pp).
  • The framework achieved very large effect sizes for curiosity (context-seeking rate) and humility (hedging) metrics.
  • Appropriate clarifying questions increased dramatically, from 7.8% (GPT-4.1-mini) and 0.0% (GPT-4o-mini) at baseline to 97.3% and 73.5% respectively.

Conclusions:

  • LLMs can be reliably constrained to operate within epistemic boundaries using structured uncertainty decomposition and virtue-aligned rules.
  • BODHI offers a viable pathway towards safer and more reliable clinical AI deployment.
  • The framework effectively promotes information-gathering behavior in AI systems, crucial for clinical settings.