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

arXiv: https://arxiv.org/abs/2608.16890 · HTML: https://mlsanity.com/paper/2608.16890/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 20 of its 31 references that are in the map.
- First posted on arXiv 13 May 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 20 of 20)

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- [Data-Copilot: Bridging Billions of Data and Humans with Autonomous Workflow](https://mlsanity.com/paper/2306.07209/) (2023)
- [MASAI: Modular Architecture for Software-engineering AI Agents](https://mlsanity.com/paper/2406.11638/) (2024)
- [ClinicalAgent: Clinical Trial Multi-Agent System with Large Language Model-based Reasoning](https://mlsanity.com/paper/2404.14777/) (2024)
- [Using Large Language Models to Generate Clinical Trial Tables and Figures](https://mlsanity.com/paper/2409.12046/) (2024)

## Abstract (arXiv)

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.