Neurosymbolic Clinical Trial Matching via LLM-Driven Abduction and Logical Verification

The reliance on unstructured free text for documenting clinical trial protocols creates a significant barrier to automated reasoning, cohort discovery, and trial simulation. The lack of formal structure obscures critical temporal phenotypes, such as dynamic eligibility criteria and event timing constraints. Although Temporal Ensemble Logic (TEL) offers an expressive framework for modeling these elements, manual encoding remains a prohibitive bottleneck. We introduce the CT-TEL workflow: a scalable pipeline leveraging Large Language Models (LLMs) to translate narrative clinical protocols into TEL formulas. We applied CT-TEL to generate logical models for 23 real-world trials from ClinicalTrials.gov. We evaluated translation fidelity via a back-translation approach, using LLMs to convert TEL formulas back into natural language and measuring semantic similarity against source texts. The resulting semantic retention suggests that LLMs may offer a pathway for mapping informal protocols to computable logic, providing preliminary evidence toward scalable clinical trial emulation within the emerging "Symbolic Biomedicine" paradigm championed by the corresponding author.

Clinical decision-making requires reasoning over incomplete, imprecise, and linguistically expressed patient narratives. While large language models (LLMs) excel at extracting latent information from natural language, they lack the verifiability and interpretability essential for trustworthy medical AI. We propose a neuro-symbolic reasoning framework that aligns LLMs with formal logic to enable explainable and formally verifiable medical diagnosis. Patient descriptions and clinical guidelines are embedded into a neural knowledge base, where LLMs extract structured medical entities, temporal relations, and fuzzy symptom patterns, which are decoded into a symbolic knowledge base expressed in fuzzy logic and declarative rules. We perform two-stage reasoning: (1) inductive symbolic generalization to capture diagnostic patterns from encoded narratives, and (2) inference verification via a logic programming engine to derive and validate diagnoses consistent with clinical standards. Each symptom is treated as a fuzzy predicate with probabilistic weights, and inference paths are auditable, adjustable, and compatible with physician feedback. Unlike purely statistical methods, our system supports iterative refinement: misalignment between LLM-generated diagnoses and ground truth can be traced, explained, and corrected through formal rules. By combining logic-based transparency, LLM adaptability, and probabilistic robustness, the framework enables human-aligned healthcare inference with strong generalization and verifiable, step-by-step reasoning chains. We validate our framework on public benchmarks, demonstrating effective reconciliation of symbolic reasoning and LLMs with real-world clinical narratives. Results show performance comparable to state-of-the-art LLMs, while additionally providing interpretable reasoning paths and formally verifiable diagnostic conclusions.

LLMs deployed in high-stakes domains face fundamental reliability challenges: hallucinations, inconsistencies, and privacy vulnerabilities introduce unacceptable risks where errors carry legal, financial, or safety consequences. This paper presents a hybrid verification architecture combining formal symbolic methods with neural semantic analysis to provide complementary guarantees for LLM-generated content. This architecture employs logical reasoning for input verification, leveraging completeness properties to provide decidable guarantees on structured requirements. For output validation, embedding-based semantic similarity detects contextual hallucinations where formal methods lack expressiveness. This separation is realized in a parallel, actor-based pipeline, addressing limitations of prompt-based self-verification approaches, which inherit the distributional biases that produce hallucinations. The proposed architecture and type-aware verification method are validated with HAIMEDA, a real-world medical device damage assessment reporting system developed through Action Design Research. Evaluation shows hallucination detection rates of over 83% for structured entities and 72% for semantic fabrications, with a 30% reduction in report creation time, demonstrating that neuro-symbolic architectures can provide principled safeguards for LLM deployment in data-sensitive domains.