# End-to-End Agentic RAG System Training for Traceable Diagnostic Reasoning

arXiv: https://arxiv.org/abs/2508.15746 · HTML: https://mlsanity.com/paper/2508.15746/

## Key facts

- Cited by 10 papers in the map (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 40 of its 84 references that are in the map.
- First posted on arXiv 21 Aug 2025.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)
- Retrieval-augmented generation / [Medical and biomedical RAG](https://mlsanity.com/rag/medical-and-biomedical-rag/)
- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 30 of 40)

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Models](https://mlsanity.com/paper/2402.03300/) (2024)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Efficient Memory Management for Large Language Model Serving with PagedAttention](https://mlsanity.com/paper/2309.06180/) (2023)
- [Qwen2.5 Technical Report](https://mlsanity.com/paper/2412.15115/) (2024)
- [GPT-4o System Card](https://mlsanity.com/paper/2410.21276/) (2024)
- [Retrieval-Augmented Generation for Large Language Models: A Survey](https://mlsanity.com/paper/2312.10997/) (2023)
- [HybridFlow: A Flexible and Efficient RLHF Framework](https://mlsanity.com/paper/2409.19256/) (2024)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [SGLang: Efficient Execution of Structured Language Model Programs](https://mlsanity.com/paper/2312.07104/) (2023)
- [MedGemma Technical Report](https://mlsanity.com/paper/2507.05201/) (2025)
- [Benchmarking Retrieval-Augmented Generation for Medicine](https://mlsanity.com/paper/2402.13178/) (2024)
- [MEDITRON-70B: Scaling Medical Pretraining for Large Language Models](https://mlsanity.com/paper/2311.16079/) (2023)
- [Agentic Retrieval-Augmented Generation: A Survey on Agentic RAG](https://mlsanity.com/paper/2501.09136/) (2025)
- [MedCPT: Contrastive Pre-trained Transformers with Large-scale PubMed Search Logs for Zero-shot Biomedical Information Retrieval](https://mlsanity.com/paper/2307.00589/) (2023)
- [MedDialog: Two Large-scale Medical Dialogue Datasets](https://mlsanity.com/paper/2004.03329/) (2020)
- [Towards Accurate Differential Diagnosis with Large Language Models](https://mlsanity.com/paper/2312.00164/) (2023)
- [MMedAgent: Learning to Use Medical Tools with Multi-modal Agent](https://mlsanity.com/paper/2407.02483/) (2024)
- [Medical Graph RAG: Towards Safe Medical Large Language Model via Graph Retrieval-Augmented Generation](https://mlsanity.com/paper/2408.04187/) (2024)
- [MMed-RAG: Versatile Multimodal RAG System for Medical Vision Language Models](https://mlsanity.com/paper/2410.13085/) (2024)
- [Towards Conversational Diagnostic AI](https://mlsanity.com/paper/2401.05654/) (2024)
- [Can GPT-4V(ision) Serve Medical Applications? Case Studies on GPT-4V for Multimodal Medical Diagnosis](https://mlsanity.com/paper/2310.09909/) (2023)
- [RAGChecker: A Fine-grained Framework for Diagnosing Retrieval-Augmented Generation](https://mlsanity.com/paper/2408.08067/) (2024)
- [TxAgent: An AI Agent for Therapeutic Reasoning Across a Universe of Tools](https://mlsanity.com/paper/2503.10970/) (2025)
- [An Agentic System for Rare Disease Diagnosis with Traceable Reasoning](https://mlsanity.com/paper/2506.20430/) (2025)
- [Large Language Models for Disease Diagnosis: A Scoping Review](https://mlsanity.com/paper/2409.00097/) (2024)
- [RareBench: Can LLMs Serve as Rare Diseases Specialists?](https://mlsanity.com/paper/2402.06341/) (2024)
- [CoD, Towards an Interpretable Medical Agent using Chain of Diagnosis](https://mlsanity.com/paper/2407.13301/) (2024)
- [Baichuan-M1: Pushing the Medical Capability of Large Language Models](https://mlsanity.com/paper/2502.12671/) (2025)
- [Towards Evaluating and Building Versatile Large Language Models for Medicine](https://mlsanity.com/paper/2408.12547/) (2024)

## Built on by (most cited first, 10 of 10)

- [CXRAgent: Director-Orchestrated Multi-Stage Reasoning for Chest X-Ray Interpretation](https://mlsanity.com/paper/2510.21324/) (2025)
- [Medical Reasoning with Large Language Models: A Survey and MR-Bench](https://mlsanity.com/paper/2604.08559/) (2026)
- [Joint Optimization of Reasoning and Dual-Memory for Self-Learning Diagnostic Agent](https://mlsanity.com/paper/2604.07269/) (2026)
- [Proactive Reasoning-with-Retrieval Framework for Medical Multimodal Large Language Models](https://mlsanity.com/paper/2510.18303/) (2025)
- [Teaching agentic AI to generalize expert diagnostic reasoning in rare diseases](https://mlsanity.com/paper/2606.16149/) (2026)
- [From Exposure to Internalization: Dual-Stream Calibration for In-context Clinical Reasoning](https://mlsanity.com/paper/2604.06262/) (2026)
- [When Cases Get Rare: A Retrieval Benchmark for Off-Guideline Clinical Question Answering](https://mlsanity.com/paper/2605.21807/) (2026)
- [C-MIG: Multi-view Information Gain-based Retrieval-Augmented Generation for Clinical Diagnosis Reasoning](https://mlsanity.com/paper/2605.27860/) (2026)
- [CAREAgent: Clinical Agent with Structured Reasoning and Tool-Integrated for Order Generation](https://mlsanity.com/paper/2606.01094/) (2026)
- [A safety-oriented hypothetico-deductive framework for AI-assisted differential diagnosis](https://mlsanity.com/paper/2607.08038/) (2026)

## Abstract (arXiv)

The integration of Large Language Models (LLMs) into healthcare is constrained by knowledge limitations, hallucinations, and a disconnect from Evidence-Based Medicine (EBM). While Retrieval-Augmented Generation (RAG) offers a solution, current systems often rely on static workflows that miss the iterative, hypothetico-deductive reasoning of clinicians. To address this, we introduce Deep-DxSearch, an agentic RAG system trained end-to-end via reinforcement learning (RL) for traceable diagnostic reasoning. Deep-DxSearch acts as an active investigator, treating the LLM as an agent within an environment of 16,000+ guideline-derived disease profiles, 150,000+ patient records for case-based reasoning, and over 27 million biomedical documents. Using soft verifiable rewards that co-optimize retrieval and reasoning, the model learns to formulate queries, evaluate evidence, and refine searches to close diagnostic gaps. Experiments show our end-to-end RL framework consistently outperforms prompt-engineering and training-free RAG methods. On in-distribution (ID) and out-of-distribution (OOD) benchmarks for common and rare diseases, Deep-DxSearch surpasses strong baselines-including GPT-4o, DeepSeek-R1, and medical-specific frameworks-achieving an average accuracy gain of 22.7% over the second-best model. In validation with 150 real-world cases, Deep-DxSearch boosts physicians' average diagnostic accuracy from 45.6% to 69.1%. These results indicate that evolving agentic systems to leverage statistical regularities in large-scale healthcare data is key for trustworthy diagnostic assistants. All data, code, and checkpoints are available at https://qiaoyu-zheng.github.io/Deep-DxSearch.