AOP-Wiki EMOD 3.0: Data Model Expansions and Content Evaluation Framework for Using Agentic AI to Improve Integration between AOPs and New Approach Methodologies (NAMs)

The Observational Medical Outcomes Partnership Common Data Model (OMOP CDM), maintained by the Observational Health Data Sciences and Informatics (OHDSI) collaboration, enabled the harmonisation of electronic health records data of nearly one billion patients in 83 countries. Yet generating real-world evidence (RWE) from these repositories remains a manual process requiring clinical, epidemiological and technical expertise. LLMs and multi-agent systems have shown promise for clinical tasks, but RWE automation exposes a fundamental challenge: agentic systems introduce emergent behaviours, coordination failures and safety risks that existing approaches fail to govern. No infrastructure exists to ensure agentic RWE generation is flexible, safe and auditable across the lifecycle. We introduce FastOMOP, an open-source multi-agent architecture that addresses this gap by separating three infrastructure layers, governance, observability and orchestration, from pluggable agent-teams. Governance is enforced at the process boundary through deterministic validation independent of agent reasoning, ensuring no compromised or hallucinating agent can bypass safety controls. Agent teams for phenotyping, study design and statistical analysis inherit these guarantees through controlled tool exposure. We validated FastOMOP using a natural-language-to-SQL agent team across three OMOP CDM datasets: synthetic data from Synthea, MIMIC-IV and a real-world NHS dataset from Lancashire Teaching Hospitals (IDRIL). FastOMOP achieved reliability scores of 0.84-0.94 with perfect adversarial and out-of-scope block rates, demonstrating process-boundary governance delivers safety guarantees independent of model choice. These results indicate that the reliability gap in RWE deployment is architectural rather than model capability, and establish FastOMOP as a governed architecture for progressive RWE automation.

Clinical artificial intelligence is increasingly embedded in real-world care, yet existing safety mechanisms are poorly suited to reconstructing and learning from individual AI-related errors and near-misses. Aggregate model monitoring can identify performance changes, and traditional patient safety reporting can capture adverse events, but neither is designed to explain how risk emerges across the interaction among AI systems, clinicians, workflows, and institutional controls. We propose AI Morbidity and Mortality (AI M&M), a structured, blameless framework for case-based review of clinical AI failures. The framework combines standardized case intake, evidence preservation and investigator-level reconstruction, tool-in-loop attribution, and corrective-action tracking. Each event is classified across four linked dimensions: Trigger - Mechanism - Clinical Pathway - Corrective Action, separating the condition that exposed a vulnerability from the process that produced risk, its consequence for care, and the remediation assigned. We demonstrate the framework using five illustrative outpatient medication and clinical decision-support cases; two clinician reviewers independently applied all four classification axes and reached agreement across all 20 axis-level classifications. AI M&M is intended to complement, rather than replace, model monitoring, patient safety reporting, and regulatory oversight by converting individual AI-in-workflow failures into actionable institutional learning. Prospective evaluation across institutions, AI systems, and clinical settings is needed.

Drug development and pharmacovigilance are frequently bottlenecked by legacy clinical reporting pipelines. These monolithic systems encode regulatory-grade logic but resist AI integration by producing opaque output with no machine-readable intermediate layer. Existing modernization approaches force a choice between full rewrites and incremental refactoring that preserves structural barriers. We present a non-destructive methodological framework achieving AI-driven pharmacoinformatics readiness without altering legacy source code. A metadata layer--comprising a bridge map, a typed Intermediate Representation (IR), and an orchestrator--wraps existing components and re-exposes their outputs as structured data consumable by LLMs. It enables optional incremental consolidation, replacing selected legacy components with metadata-configured core routines while the remainder operates unchanged. Validated on a 558-component SAS reporting library (373,000 lines of code), the framework demonstrated immediate AI-readiness under coexistence mode, yielding machine-readable output. Where consolidation was elected, the modernized core achieved a 92% reduction in proprietary code. Parity validation on 14 report types from a Phase III study achieved cell-level parity of 80% or above on 11 reports (mean 82.7%, best 99.2%). A benchmark using CDISC CDISCPilot01 data achieved 100% parity across 5 reports. LLM experiments confirmed the IR enables automated pharmacovigilance, table summarization, and trial configuration generation. The framework offers a regulation-aware path to AI-integrated clinical reporting, accelerating drug development without interrupting regulatory submissions.