Introduction: NICE guidelines provide evidence-based recommendations for clinical care but remain largely in unstructured natural language. Existing approaches to converting them into computable representations often focus on individual diseases, require substantial manual encoding, and do not scale. Large language models (LLMs) may enable much of this translation to be automated. Methods: We present an end-to-end approach that converts textual clinical guidelines into executable models capable of generating explainable, patient-specific recommendations. A stepwise LLM-based transformation with in-context examples produces human-inspectable intermediate artifacts. We apply the approach to NICE pancreatic and lung cancer guidelines, use expert review to assess rule alignment, and evaluate the executable pancreatic cancer model on 20 patient vignettes. Results: Expert review showed strong alignment between the source guidelines and generated executable models. Most discrepancies were partial omissions rather than incorrect logic, while hallucinated or fundamentally incorrect rules were rare. On the patient vignettes, the executable model achieved an F1 score of 82.5%. Conclusion: LLMs can transform natural-language NICE guidelines into interpretable, executable models that preserve guideline structure, support transparent inspection and modification, and generate patient-specific recommendations. These findings demonstrate the feasibility of scalable automated generation of computable clinical guidelines.
Large language models have facilitated knowledge graph (KG) construction from clinical guidelines, but extracted triples vary in structural validity and evidential support. Meanwhile, graph-augmented question answering (QA) systems typically optimize query relevance during retrieval, with limited reuse of quality information produced during KG construction. This creates a disconnect between construction-time quality control and inference-time evidence use. We investigate whether construction-time triple quality can serve as a persistent signal for downstream evidence selection and presentation. We propose a quality-aware framework that models structural conformance (SchemaConf) and evidential support (EvidScore) as complementary dimensions and fuses them into a per-triple quality signal, Q(t). Rather than using quality solely for filtering, the framework retains Q(t) and derived quality tiers as graph attributes and propagates them into quality-weighted subgraph retrieval and tier-conditioned evidence prompting, while preserving passage-level provenance. Experiments on Chinese diabetes clinical guidelines show that the utility of the quality signal is distribution dependent. Under cross-version and cross-model shift, the fused Q(t) provides stronger triple-quality discrimination than either component alone (AUC 0.748 vs. 0.703 for EvidScore and 0.645 for SchemaConf). In guideline-grounded QA, propagating construction-time quality reduces required-knowledge omission from 16.3% to 5.3% and conflicting outputs from 16.3% to 2.7%, with an evidence-grounded precision of 81.6% and near-zero invalid citations. Blinded clinician ratings favor the full framework over no retrieval (4.68 vs. 4.21 on a five-point scale) and approach the oracle condition (4.80), while cross-generator experiments show consistent trends.
Treatment planning in precision oncology requires synthesizing heterogeneous patient information with rapidly evolving clinical guidelines to ensure guideline-concordant care. While large language models (LLMs) show promise in many diagnostic tasks, their adoption for high-stakes treatment planning is hindered by complex reasoning, adherence to timely clinical guidelines, and safety concerns. In this study, we present GatorOnco, an agentic LLM for colorectal cancer (CRC) treatment planning. GatorOnco is developed using a total of 282 billion tokens of biomedical text, including healthcare system-scale clinical text comprising 166 billion tokens from UF Health. We implemented a domain-adaptation method that integrates pre-training, model merging, a two-stage post-training approach, and agent-based reinforcement learning. An agentic retrieval-augmented generation (RAG) approach dynamically integrates time-sensitive clinical guidelines into the reasoning process. In a blind, randomized clinical evaluation conducted by five UF Health oncologists, GatorOnco significantly outperformed open-source LLMs (P < 0.01) and achieved expert-level performance comparable to UF Health oncologists. Compared with expert oncologists, GatorOnco received significantly higher ratings for readability (4.46 vs. 4.19, P < 0.01) and completeness (3.91 vs. 3.52, P < 0.01), while showing statistically comparable performance in correctness (4.09 vs. 4.11, P = 0.921), currency (4.04 vs. 3.98, P = 0.478), and safety (4.22 vs. 4.22, P = 0.999). These findings demonstrate that integrating agentic reasoning with large-scale domain adaptation can help bridge the gap for generative AI in high-stakes cancer treatment planning.
Causal diagnostic models must explain how conclusions follow from evidence because diagnoses guide repairs and treatments. Yet serious cases are scarce, records rarely contain reasoning paths, and data transfer poorly across configurations, complicating local deployment. We present DiagLoop, a counterfactual data flywheel that converts codified physical relations or clinical guidelines, authored once per mechanism family, into training supervision beyond recorded cases. A training-only teacher proposes counterfactual worlds by varying causes, contexts, and observations, while an independent hybrid checker admits only valid worlds. The student reasons through symptom abstraction, causal-chain construction, and root-cause attribution. Stage-specific criteria identify its earliest failure. For nonterminal failures, a bounded repair probes downstream competence, and the resulting weakness profile guides subsequent data generation. Stage-localized reinforcement learning updates only the model-generated continuation, while replay and preservation reduce forgetting. The same criteria govern admission, attribution, reward, and regeneration through checks separate from the proposer. Using only synthesized scenarios and no case-level expert reasoning annotations, the resulting 8B model improves strict path correctness over the strongest conventional baseline. Gains are 11.6 points across eight industrial systems and 5.5 points across ten disease categories. Gains over a deranged-routing control are 3.9 and 2.3 points, respectively. The model also exceeds the evaluated proprietary references in both domains, even when they receive few-shot examples or the specification in context.
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.
Large language models (LLMs) can produce clinically fluent recommendations for type 2 diabetes while failing to satisfy guideline constraints or explicitly justify lifestyle-related glycemic claims. We present T2D-Bench, a reproducible benchmark and evidence-gated evaluation framework for testing whether LLM outputs satisfy explicit, graph-checkable evidence requirements. T2D-Bench is built on a multi-layer clinical-lifestyle knowledge graph that combines a biomedical spine (UMLS, DrugBank, SIDER), computable ADA Standards of Care rules, and lifestyle knowledge connected through a mechanistic bridge to glycemic laboratory effects. Across 100 structured vignettes spanning diagnosis, medication safety, and adversarial lifestyle conflicts, baseline outputs failed benchmark-defined evidence-path checks in 35% of cases for GPT-4o-mini and 33% for GPT-4o. The evidence gate detects unsupported omissions and uses constrained revision to bring outputs into verifier-level compliance with benchmark-defined evidence requirements. These results show that computable evidence constraints can make unsupported clinical omissions explicit, measurable, and correctable in diabetes-focused LLM outputs.
Giorgio Leonardi, Stefania Montani, Manuel Striani +2cs.AI
Objective: Conformance checking in healthcare seeks to assess whether patient care pathways adhere to clinical guidelines. However, its practical application often depends on the availability of formal, machine-interpretable representations of guidelines, such as Computer-Interpretable Guidelines (CIGs), which are seldom available in real-world clinical settings. Methods: This work introduces a modular framework based on the orchestration of Large Language Models (LLMs) to support medical conformance checking directly from unstructured clinical and guideline texts, without requiring predefined CIGs. The proposed architecture integrates multiple LLMs and supporting components to extract patient traces from clinical discharge letters, identify normative rules from textual clinical guidelines, translate these rules into executable scripts, and compute a Trace Conformance Indicator to quantify compliance within the event log. Results: The framework was implemented and evaluated in the stroke care domain at the neurological ward of Alessandria Hospital. Hundreds of patient traces were automatically extracted from hospital data and assessed against 50 rules derived from the reference guideline. The analysis showed that more than 86\% of the available traces were conformant. Conclusion: The results demonstrate the feasibility of using orchestrated LLMs for practical healthcare conformance analysis. At the same time, the study provides evidence of a high level of adherence to stroke care guidelines at Alessandria Hospital.