Jaime Yan | Searcharxiv

arXiv2026

A Non-Destructive Methodological Framework for Modernizing Legacy Clinical Reporting Systems for AI-Driven Pharmacoinformatics: A SAS Case Study

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.

cs.SE↗

arXiv2026

GxP-Agent: Process-DAG Topology for Reliable Clinical Trial Programming with LLM Agents

Clinical trial programming -- transforming study protocols into analysis-ready datasets under CDISC standards -- is a bottleneck in regulatory submissions, yet LLM-based code generation fails catastrophically on this task: across 11 single-shot attempts with five frontier models, none produces a valid subject-level analysis dataset. We introduce GxP-Agent, a multi-agent system that encodes regulatory process ordering as a directed acyclic graph (DAG), decomposing monolithic dataset generation into 15 domain-specific nodes executed by worker agents with pharmaverse skill context, validation gates, and conditional retry. On CDISC-Bench, a new execution-based benchmark built from the FDA pilot submission CDISCPilot01 (254 subjects, 49 ground-truth ADSL variables), GxP-Agent with Claude Sonnet 4.6 achieves 100% structural match (49/49 variables, 254 correct records) across three independent runs, compared to 59.2% for the best retrieval-augmented baseline and 0% for all single-agent and flat multi-agent approaches. The DAG topology also enables weaker models: GPT-4.1 achieves 59.2% mean structural match under the same DAG, where it scores 0% under every other architecture. The approach generalizes to ADAE (adverse events; 9-node branching DAG, 55 variables, 1,191 records), achieving 100% structural match on the first attempt. These results demonstrate that encoding domain process knowledge as graph topology -- rather than relying on LLM reasoning alone -- is a key enabler for reliable, GxP-compliant clinical trial programming.

cs.AI↗