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Updated: Jun 20, 2026

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Evidence-based AI: from trailblazer to trustblazer?
Thomas Luechtefeld1, Thomas Hartung2,3
1Insilica Inc., Rockville, MD, United States.
Abstract:
Agentic AI systems can plan, call tools, and coordinate specialized sub-agents, enabling multi-step scientific workflows that exceed what single-model text generation can reliably deliver. Yet in high-stakes domains such as regulatory science and toxicology, fluent outputs are not sufficient: adoption hinges on traceability, reproducibility, context-of-use validity, and explicit uncertainty communication. This perspective argues that evidence-based medicine and evidence-based toxicology provide a mature epistemic scaffold for making agentic AI trustworthy by design. We propose an Evidence-based Agent Stack that decomposes end-to-end tasks into protocolized roles (question framing, retrieval, screening, extraction, risk-of-bias appraisal, synthesis, mechanistic/causal integration, uncertainty assessment, and evidence-to-decision translation) with mandatory provenance and versioning. Anchoring agentic workflows in systematic review practice, risk-of-bias frameworks, and emerging regulatory principles (e.g., TREAT and e-validation) can turn "trailblazing" AI into "trustblazing" AI: systems whose outputs are auditable, updateable, and aligned with decision accountability.
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