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

Abstract: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.