# Rethinking Retrieval-Augmented Generation for Medicine: A Large-Scale, Systematic Expert Evaluation and Practical Insights

arXiv: https://arxiv.org/abs/2511.06738 · HTML: https://mlsanity.com/paper/2511.06738/

## Key facts

- Cited by 6 papers in the map (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 18 of its 117 references that are in the map.
- First posted on arXiv 10 Nov 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/)

## Builds on (most cited first, 18 of 18)

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [GPT-4o System Card](https://mlsanity.com/paper/2410.21276/) (2024)
- [Qwen Technical Report](https://mlsanity.com/paper/2309.16609/) (2023)
- [Gemini 1.5: Unlocking multimodal understanding across millions of tokens of context](https://mlsanity.com/paper/2403.05530/) (2024)
- [Search-R1: Training LLMs to Reason and Leverage Search Engines with Reinforcement Learning](https://mlsanity.com/paper/2503.09516/) (2025)
- [Qwen3 Embedding: Advancing Text Embedding and Reranking Through Foundation Models](https://mlsanity.com/paper/2506.05176/) (2025)
- [Unsupervised Dense Information Retrieval with Contrastive Learning](https://mlsanity.com/paper/2112.09118/) (2021)
- [Towards General Text Embeddings with Multi-stage Contrastive Learning](https://mlsanity.com/paper/2308.03281/) (2023)
- [Agentic Retrieval-Augmented Generation: A Survey on Agentic RAG](https://mlsanity.com/paper/2501.09136/) (2025)
- [Medical Hallucinations in Foundation Models and Their Impact on Healthcare](https://mlsanity.com/paper/2503.05777/) (2025)
- [OpenScholar: Synthesizing Scientific Literature with Retrieval-augmented LMs](https://mlsanity.com/paper/2411.14199/) (2024)
- [A Comprehensive Survey of Retrieval-Augmented Generation (RAG): Evolution, Current Landscape and Future Directions](https://mlsanity.com/paper/2410.12837/) (2024)
- [Query Expansion by Prompting Large Language Models](https://mlsanity.com/paper/2305.03653/) (2023)
- [Rowen: Adaptive Retrieval-Augmented Generation for Hallucination Mitigation in LLMs](https://mlsanity.com/paper/2402.10612/) (2024)
- [MedCite: Can Language Models Generate Verifiable Text for Medicine?](https://mlsanity.com/paper/2506.06605/) (2025)
- [Integrating UMLS Knowledge into Large Language Models for Medical Question Answering](https://mlsanity.com/paper/2310.02778/) (2023)
- [Enhancing Large Language Models with Domain-specific Retrieval Augment Generation: A Case Study on Long-form Consumer Health Question Answering in Ophthalmology](https://mlsanity.com/paper/2409.13902/) (2024)
- [Reviewing Clinical Knowledge in Medical Large Language Models: Training and Beyond](https://mlsanity.com/paper/2502.20988/) (2025)

## Built on by (most cited first, 6 of 6)

- [EHR-RAG: Bridging Long-Horizon Structured Electronic Health Records and Large Language Models via Enhanced Retrieval-Augmented Generation](https://mlsanity.com/paper/2601.21340/) (2026)
- [LegalGraphRAG: Multi-Agent Graph Retrieval-Augmented Generation for Reliable Legal Reasoning](https://mlsanity.com/paper/2605.28120/) (2026)
- [From Compound Figures to Composite Understanding: Developing a Multi-Modal LLM from Biomedical Literature with Medical Multiple-Image Benchmarking and Validation](https://mlsanity.com/paper/2511.22232/) (2025)
- [DiscoVerse: Multi-Agent Pharmaceutical Co-Scientist for Traceable Drug Discovery and Reverse Translation](https://mlsanity.com/paper/2511.18259/) (2025)
- [Eliciting Intrinsic Hallucinations in LLMs via Semantically Equivalent Adversarial Attacks](https://mlsanity.com/paper/2608.04286/) (2026)
- [CLEAR: Cross-Source Evidence Adjudication for Large Language Models in Medicine](https://mlsanity.com/paper/2609.16301/) (2026)

## Abstract (arXiv)

Large language models (LLMs) are transforming the landscape of medicine, yet two fundamental challenges persist: keeping up with rapidly evolving medical knowledge and providing verifiable, evidence-grounded reasoning. Retrieval-augmented generation (RAG) has been widely adopted to address these limitations by supplementing model outputs with retrieved evidence. However, whether RAG reliably achieves these goals remains unclear. Here, we present the most comprehensive expert evaluation of RAG in medicine to date. Eighteen medical experts contributed a total of 80,502 annotations, assessing 800 model outputs generated by GPT-4o and Llama-3.1-8B across 200 real-world patient and USMLE-style queries. We systematically decomposed the RAG pipeline into three components: (i) evidence retrieval (relevance of retrieved passages), (ii) evidence selection (accuracy of evidence usage), and (iii) response generation (factuality and completeness of outputs). Contrary to expectation, standard RAG often degraded performance: only 22% of top-16 passages were relevant, evidence selection remained weak (precision 41-43%, recall 27-49%), and factuality and completeness dropped by up to 6% and 5%, respectively, compared with non-RAG variants. Retrieval and evidence selection remain key failure points for the model, contributing to the overall performance drop. We further show that simple yet effective strategies, including evidence filtering and query reformulation, substantially mitigate these issues, improving performance on MedMCQA and MedXpertQA by up to 12% and 8.2%, respectively. These findings call for re-examining RAG's role in medicine and highlight the importance of stage-aware evaluation and deliberate system design for reliable medical LLM applications.