# GuideSkill: Evolving Executable LLM Agent Skills for Guideline-Grounded Clinical Reasoning

arXiv: https://arxiv.org/abs/2607.26160 · HTML: https://mlsanity.com/paper/2607.26160/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning.
- Builds on 23 of its 36 references that are in the map.
- First posted on arXiv 28 Jul 2026.

## Placed in

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

## Builds on (most cited first, 23 of 23)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Models](https://mlsanity.com/paper/2402.03300/) (2024)
- [Retrieval-Augmented Generation for Knowledge-Intensive NLP Tasks](https://mlsanity.com/paper/2005.11401/) (2020)
- [Judging LLM-as-a-Judge with MT-Bench and Chatbot Arena](https://mlsanity.com/paper/2306.05685/) (2023)
- [Efficient Memory Management for Large Language Model Serving with PagedAttention](https://mlsanity.com/paper/2309.06180/) (2023)
- [Decoupled Weight Decay Regularization](https://mlsanity.com/paper/1711.05101/) (2017)
- [MEDITRON-70B: Scaling Medical Pretraining for Large Language Models](https://mlsanity.com/paper/2311.16079/) (2023)
- [HuatuoGPT-o1, Towards Medical Complex Reasoning with LLMs](https://mlsanity.com/paper/2412.18925/) (2024)
- [Trace2Skill: Distill Trajectory-Local Lessons into Transferable Agent Skills](https://mlsanity.com/paper/2603.25158/) (2026)
- [SkillClaw: Let Skills Evolve Collectively with Agentic Evolver](https://mlsanity.com/paper/2604.08377/) (2026)
- [SKILLFOUNDRY: Building Self-Evolving Agent Skill Libraries from Heterogeneous Scientific Resources](https://mlsanity.com/paper/2604.03964/) (2026)
- [MedCaseReasoning: Evaluating and learning diagnostic reasoning from clinical case reports](https://mlsanity.com/paper/2505.11733/) (2025)
- [ER-Reason: A Benchmark Dataset for LLM Clinical Reasoning in the Emergency Room](https://mlsanity.com/paper/2505.22919/) (2025)
- [MedDM:LLM-executable clinical guidance tree for clinical decision-making](https://mlsanity.com/paper/2312.02441/) (2023)
- [Enhancing Large Language Models for Clinical Decision Support by Incorporating Clinical Practice Guidelines](https://mlsanity.com/paper/2401.11120/) (2024)
- [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)
- [Improving Clinical Diagnosis with Counterfactual Multi-Agent Reasoning](https://mlsanity.com/paper/2603.27820/) (2026)
- [Training and Evaluation of Guideline-Based Medical Reasoning in LLMs](https://mlsanity.com/paper/2512.03838/) (2025)
- [MedGuideX: Internalizing Decision Logic from Executable Guidelines into Large Language Models for Clinical Reasoning](https://mlsanity.com/paper/2605.26567/) (2026)
- [CPGPrompt: Translating Clinical Guidelines into LLM-Executable Decision Support](https://mlsanity.com/paper/2601.03475/) (2026)
- [An Empirical Study of Agent Skills for Healthcare: Practice, Gaps, and Governance](https://mlsanity.com/paper/2605.02709/) (2026)

## Built on by (most cited first, 1 of 1)

- [MedRouter: Demystifying Knowledge Differences Across Medical LLMs for Routing-Based Reasoning](https://mlsanity.com/paper/2609.33119/) (2026)

## Abstract (arXiv)

Clinical practice guidelines (CPGs) encode diagnostic criteria, but LLM systems typically retrieve guideline text or absorb it through training rather than execute its rules. We introduce GuideSkill, an external reasoning layer that compiles disease-specific criteria into executable functions returning ordinal diagnostic-support scores. GuideSkill-Zero is initialized from guidelines, while GuideSkill-Evo uses case--diagnosis pairs to refine covered skills and add missing diagnoses. At inference, an LLM proposes a differential diagnosis, grounds the features required by each matched skill, and fuses its ranking with the executed skill scores. Across four benchmarks and four backbones, GuideSkill-Zero improves macro-average accuracy over guideline RAG by 13.45% on average. GuideSkill-Evo achieves the highest macro-average for every backbone, improves over direct inference by 18.49% relatively, and increases gold-label skill coverage from 56.5% to 99.5%. On Qwen3.5-9B, it also exceeds the strongest parameter-update baseline by 11.16% without updating the backbone. Expert evaluation further indicates that GuideSkill produces clinically sound and broadly acceptable skills, suggesting that its initialized and evolved rules are reliable and practically meaningful. These results support executable skills as a model-agnostic mechanism for combining guideline-derived procedures with case-derived diagnostic patterns.