What ICH E6(R3) actually requires for AI-assisted clinical data management

ICH E6(R3) was finalized January 6, 2025, and became effective in the EU in July 2025. It is the first revision to the GCP guideline in a decade, and its requirements for data governance, audit trails, computerized system validation, and human oversight apply directly to AI-assisted clinical data management processes.

E6(R3) requires that audit trails record who performed each action, what action was performed, when, and why. For AI systems, this means agent inference calls must be logged with the same rigor as human user actions. Human oversight of data management processes is required and cannot be delegated to automated systems. Validation must be proportionate to risk — for AI systems producing SDTM or Define-XML, the risk level is high.