A Hybrid Knowledge-Grounded Framework for Safety and Traceability in Prescription Verification

Large Language Models (LLMs) are increasingly deployed in healthcare settings, yet their tendency to hallucinate poses risks when clinical decisions are involved. This study examine whether LLMs recommend recently banned or withdrawn pharmaceuticals when answering clinical questions and tests an agent-based method for reducing such errors. We developed a five-agent "Trust but Verify" system using a single LLM backbone. To measure regulatory knowledge obsolescence, we created an adversarial dataset of 103 clinical MCQs where historically correct answers now refer to banned substances. This scale ensures statistical significance across various therapeutic classes. We evaluated three open-access model families (GPT-OSS, Llama-3, Falcon-3) under vanilla and agentic conditions. Performance was measured via pointwise score, label accuracy, Hallucination Error Rate (HER), and Component Fidelity (CF) score. We also observed clinical safety regression in proprietary models. In default configurations, all models showed high hallucination rates, consistently selecting banned drugs that matched training data patterns. Our proposed agentic architecture reduced HER by approximately 53% across models. Pointwise scores shifted from -0.25 (unsafe recommendation) toward 0.0 (appropriate refusal). The safety audit intercepted dangerous outputs even when models' parametric knowledge favored the banned substance. The proposed multi-agent framework offers a model-agnostic method for enforcing regulatory compliance that prioritizes patient safety over fluent text generation. Our work demonstrates a practical approach for deploying autonomous AI systems in safety-critical healthcare settings. It shows how real-time regulatory data can be integrated into LLM pipelines to support clinical decision-making.

Medication recommendation predicts medications for patient visits, but existing methods still face two key challenges. At the model level, traditional drug recommendation methods only predict structured drug codes with limited evidence grounding, while LLM agents can use richer clinical context but may lack safety verification and traceability. At the task level, existing benchmarks often use broad medication categories, which ignore subgroup-level safety differences and can lead to risk overestimation. We introduce the first fine-grained medication recommendation setting based on fourth-level ATC code generation. We propose Safe Prescription Agent (SafeRx-Agent), a knowledge-grounded multi-agent framework that uses patient context, external clinical knowledge, and safety verification to recommend traceable medication sets. Experimental results on MIMIC-III and MIMIC-IV datasets show that SafeRx-Agent improves fine-grained medication prediction accuracy while controlling drug interactions, contraindications, and medication set size.

Retrieval-Augmented Generation (RAG) significantly improves the factuality of Large Language Models (LLMs), yet standard pipelines often lack mechanisms to verify inter- mediate reasoning, leaving them vulnerable to hallucinations in high-stakes domains. To address this, we propose a domain-specific RAG framework that integrates explicit rea- soning and faithfulness verification. Our architecture augments standard retrieval with neural query rewriting, BGE-based cross-encoder reranking, and a rationale generation module that grounds sub-claims in specific evidence spans. We further introduce an eight-category verification taxonomy that enables fine-grained assessment of rationale faithfulness, distinguishing between explicit and implicit support patterns to facilitate structured error diagnosis. We evaluate this framework on the BioASQ and PubMedQA benchmarks, specifically analyzing the impact of dynamic in-context learning and rerank- ing under constrained token budgets. Experiments demonstrate that explicit rationale generation improves accuracy over vanilla RAG baselines, while dynamic demonstration selection combined with robust reranking yields further gains in few-shot settings. Using Llama-3-8B-Instruct, our approach achieves 89.1% on BioASQ-Y/N and 73.0% on Pub- MedQA, competitive with systems using significantly larger models. Additionally, we perform a pilot study combining human expert assessment with LLM-based verification to explore how explicit rationale generation improves system transparency and enables more detailed diagnosis of retrieval failures in biomedical question answering.