Abstract
Clinical LLMs can generate recommendations that are factually plausible yet physiologically unsafe. We investigate whether safety alignment can be improved by grounding preference optimization in structured physiological knowledge rather than text-only supervision. Methods: We propose Neurosymbolic Alignment, a training-time framework that couples a 7B clinical LLM with an HGNN-based Physiological World Model over an 847K-node biomedical knowledge graph. Candidate responses are scored using homeostatic constraints, multi-hop path plausibility, and drug-interaction penalties, and the resulting rankings drive iterative on-policy ORPO updates. Evaluation is performed on the Clinical Safety Benchmark (CSB), a 2,500-scenario benchmark for physiological constraint violations in generative clinical reasoning. Results: Relative to ORPO, the proposed method improves CSS from 69.5% to 90.8% (+21.3 pp), reduces physician-evaluated HR from 14.1% to 5.1% on the blinded subset, and improves DID from 72.8% to 91.6%. These gains are corroborated by an HGNN-independent Rule-Engine Safety Score (RSS: 86.4%, +21.2 pp over ORPO; r=0.97 concordance with CSS). The method also exceeds GPT-4 (5-shot) on all safety metrics despite a 10x parameter disadvantage, and outperforms an inference-time self-correction pipeline (SFT+SelfCorrect) by 11.4 pp CSS. Under synthetic EHR-style noise, 84.2% CSS is retained. Ablation analysis shows that HGNN scoring (-16.2 pp) and iterative training (-11.5 pp) are the dominant contributors. PhysioScore calibration against 200 clinician labels yielded ECE = 0.038 and kappa = 0.91. Conclusion: Training-time physiological grounding produces measurable and independently verifiable safety improvements in open-weight clinical LLMs under controlled evaluation. External validation on real clinical data is required to determine whether these gains transfer to deployment settings
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URL
https://arxiv.org/abs/2608.24534
