Scaling Up Formal Representation of Clinical Trial Protocols in Ensemble Logic Using LLMs: A Preliminary Study

Large Language Models (LLMs) offer a promising path to automate Clinical Trial Matching (CTM), but still struggle with the deterministic verification required for complex eligibility criteria. Conversely, purely symbolic methods provide formal rigour but break down when faced with incomplete patient records and noisy clinical evidence. To bridge this gap, we investigate a hybrid framework for CTM combining LLMs with logical verification. In particular, we introduce an abductive neurosymbolic CTM framework (αNeSy-CTM), which leverages the linguistic and world knowledge in LLMs to support reasoning over noisy and underspecified clinical text. Extensive evaluation demonstrates that αNeSy-CTM substantially outperforms standalone LLM baselines, achieving up to 30% relative improvement over zero-shot baselines. In addition, our analyses confirm the impact of abductive reasoning on CTM, with αNeSy-CTM exhibiting improved accuracy, specificity, and robustness over a non-abductive neurosymbolic setting. Furthermore, αNeSy-CTM and Chain-of-Thought (CoT) reasoning prove highly complementary, highlighting the potential for a hybrid routing policy. Ultimately, this paper demonstrates the impact of neurosymbolic methods for automating CTM, providing a path toward the next generation of auditable, LLM-driven clinical applications.

Large language models are increasingly used to summarize clinical trial results for healthcare providers, patients, and payers, but their tendency to hallucinate poses significant risks in this high-stakes context. This study introduces a benchmark evaluation framework for measuring the faithfulness of LLM-generated clinical trial summaries across three stakeholder audiences. The framework consists of 200 stratified trials drawn from the Aggregate Analysis of ClinicalTrials.gov database, evaluated using audience-specific prompt templates and a six-dimension faithfulness annotation schema. Baseline measurements were established for GPT-4o, Claude Sonnet 4.6, and Gemini 2.5 Flash across 1,800 generated summaries scored using a cross-encoder natural language inference (NLI) model. Unsupported Claims was identified as the dominant failure mode across all three models, with a mean annotation score of 1.55 out of three. A knowledge-graph-augmented retrieval system was developed and evaluated against the baseline, producing statistically significant improvements in NLI-based faithfulness scores (entailment +0.0125, faithfulness +0.0130, p < 0.0001). Improvement pathways were model-dependent, with GPT-4o improving primarily through contradiction reduction while Claude Sonnet 4.6 and Gemini 2.5 Flash improved through increased entailment.

We study clinical trial table reasoning, where answers are not directly stored in visible cells but must be reasoned from semantic understanding through normalization, classification, extraction, or lightweight domain reasoning. Motivated by the observation that current LLM approaches often suffer from "bad reasoning" under implicit planning assumptions, we focus on settings in which the model must recover implicit attributes such as therapy type, added agents, endpoint roles, or follow-up status from partially observed clinical-trial tables. We propose SCOPE (Structured Clinical hybrid Planning for Evidence retrieval in clinical trials), a multi-LLM planner-based framework that decomposes the task into row selection, structured planning, and execution. The planner makes the source field, reasoning rules, and output constraints explicit before answer generation, reducing ambiguity relative to direct prompting. We evaluate SCOPE on 1,500 hybrid reasoning questions over oncology clinical-trial tables against zero-shot, few-shot, chain-of-thought, TableGPT2, Blend-SQL, and EHRAgent. Results show that explicit multi-LLM planning improves accuracy for reasoning-based questions while offering a stronger accuracy-efficiency tradeoff than heavier agentic baselines. Our findings position clinical trial reasoning as a distinct table understanding problem and highlight hybrid planner-based decomposition as an effective solution