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.

Luechtefeld T and Hartung T (2026) Evidence-based AI: from trailblazer to trustblazer?. Front. Artif. Intell. 9:1818128. doi: 10.3389/frai.2026.1818128