# Training and Evaluation of Guideline-Based Medical Reasoning in LLMs

arXiv: https://arxiv.org/abs/2512.03838 · HTML: https://mlsanity.com/paper/2512.03838/

## Key facts

- Cited by 4 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 64 references that are in the map.
- First posted on arXiv 3 Dec 2025.

## Placed in

- LLM reasoning / [Clinical and biomedical applications](https://mlsanity.com/lr/clinical-and-biomedical-applications/)

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

- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Show Your Work: Scratchpads for Intermediate Computation with Language Models](https://mlsanity.com/paper/2112.00114/) (2021)
- [Measuring Faithfulness in Chain-of-Thought Reasoning](https://mlsanity.com/paper/2307.13702/) (2023)
- [Reasoning Models Don't Always Say What They Think](https://mlsanity.com/paper/2505.05410/) (2025)
- [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)
- [Large Language Models are Few-Shot Health Learners](https://mlsanity.com/paper/2305.15525/) (2023)
- [MedReason: Eliciting Factual Medical Reasoning Steps in LLMs via Knowledge Graphs](https://mlsanity.com/paper/2504.00993/) (2025)
- [Number Cookbook: Number Understanding of Language Models and How to Improve It](https://mlsanity.com/paper/2411.03766/) (2024)
- [Med-RLVR: Emerging Medical Reasoning from a 3B base model via reinforcement Learning](https://mlsanity.com/paper/2502.19655/) (2025)
- [ChestX-Reasoner: Advancing Radiology Foundation Models with Reasoning through Step-by-Step Verification](https://mlsanity.com/paper/2504.20930/) (2025)
- [Med-PRM: Medical Reasoning Models with Stepwise, Guideline-verified Process Rewards](https://mlsanity.com/paper/2506.11474/) (2025)
- [Disentangling Reasoning and Knowledge in Medical Large Language Models](https://mlsanity.com/paper/2505.11462/) (2025)
- [Extrapolation by Association: Length Generalization Transfer in Transformers](https://mlsanity.com/paper/2506.09251/) (2025)
- [Medical Reasoning in the Era of LLMs: A Systematic Review of Enhancement Techniques and Applications](https://mlsanity.com/paper/2508.00669/) (2025)
- [SepsisCalc: Integrating Clinical Calculators into Early Sepsis Prediction via Dynamic Temporal Graph Construction](https://mlsanity.com/paper/2501.00190/) (2024)
- [Early Prediction of Causes (not Effects) in Healthcare by Long-Term Clinical Time Series Forecasting](https://mlsanity.com/paper/2408.03816/) (2024)

## Built on by (most cited first, 4 of 4)

- [MedGuideX: Internalizing Decision Logic from Executable Guidelines into Large Language Models for Clinical Reasoning](https://mlsanity.com/paper/2605.26567/) (2026)
- [GuideSkill: Evolving Executable LLM Agent Skills for Guideline-Grounded Clinical Reasoning](https://mlsanity.com/paper/2607.26160/) (2026)
- [Reasoning4Sciences: Bridging Reasoning Language Models to All Scientific Branches](https://mlsanity.com/paper/2606.01145/) (2026)
- [Case2Flow: Bridging Patient Cases and Guideline Flowcharts through Multimodal Retrieval](https://mlsanity.com/paper/2608.26414/) (2026)

## Abstract (arXiv)

Machine learning for early prediction in medicine has recently shown breakthrough performance, however, the focus on improving prediction accuracy has led to a neglect of faithful explanations that are required to gain the trust of medical practitioners. The goal of this paper is to teach LLMs to follow medical consensus guidelines step-by-step in their reasoning and prediction process. Since consensus guidelines are ubiquitous in medicine, instantiations of verbalized medical inference rules to electronic health records provide data for fine-tuning LLMs to learn consensus rules and possible exceptions thereof for many medical areas. Consensus rules also enable an automatic evaluation of the model's inference process regarding its derivation correctness (evaluating correct and faithful deduction of a conclusion from given premises) and value correctness (comparing predicted values against real-world measurements). We exemplify our work using the complex Sepsis-3 consensus definition. Our experiments show that small fine-tuned models outperform one-shot learning of considerably larger LLMs that are prompted with the explicit definition and models that are trained on medical texts including consensus definitions. Since fine-tuning on verbalized rule instantiations of a specific medical area yields nearly perfect derivation correctness for rules (and exceptions) on unseen patient data in that area, the bottleneck for early prediction is not out-of-distribution generalization, but the orthogonal problem of generalization into the future by forecasting sparsely and irregularly sampled clinical variables. We show that the latter results can be improved by integrating the output representations of a time series forecasting model with the LLM in a multimodal setup.