Retrieval-Augmented LLMs for Evidence Localization in Clinical Trial Recruitment from Longitudinal EHR Narratives

Patient-trial matching requires reasoning over long, heterogeneous electronic health records (EHRs) and complex eligibility criteria, posing significant challenges for scalability, generalization, and computational efficiency. Existing approaches either rely on full-document processing with large language models (LLMs), which is computationally expensive, or use traditional machine learning methods that struggle to capture unstructured clinical narratives. In this work, we propose a lightweight framework that combines retrieval-augmented generation and large language model-based modeling for scalable patient-trial matching. The framework explicitly separates two key components: retrieval-augmented generation is used to identify clinically relevant segments from long EHRs, reducing input complexity, while large language models are used to encode these selected segments into informative representations. These representations are further refined through dimensionality reduction and modeled using lightweight predictors, enabling efficient and scalable downstream classification. We evaluate the proposed approach on multiple public benchmarks (n2c2, SIGIR, TREC 2021/2022) and a real-world multimodal dataset from Mayo Clinic (MCPMD). Results show that retrieval-based information selection significantly reduces computational burden while preserving clinically meaningful signals. We further demonstrate that frozen LLMs provide strong representations for structured clinical data, whereas fine-tuning is essential for modeling unstructured clinical narratives. Importantly, the proposed lightweight pipeline achieves performance comparable to end-to-end LLM approaches with substantially lower computational cost.

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.

Screening in systematic reviews (SRs) is manual and time-consuming. Prior work has explored large language models (LLMs) for automating this step, but LLMs are evolving rapidly, so earlier performance claims may no longer accurately reflect their screening performance. We used an existing software engineering SR screening benchmark (SESR-Eval) as our data. We also power-sampled a new, smaller dataset (SESR-Eval-Mini) that allows evaluation at lower costs. Using this data, we evaluated eight new LLMs for screening performance. Additionally, we tested different prompts, analyzed LLM agreement in screening decisions and criteria, and examined the effect of refining the inclusion and exclusion criteria on screening performance. The eight new LLMs performed marginally better than the seven old ones: avg. MCC across secondary studies rose from 0.347 to 0.365. Differences between secondary studies are still bigger than between LLMs. Computing the overall screening decision from criterion-level decisions degraded screening performance only slightly. LLMs generally agree with each other in their corresponding screening decisions (mean Gwet's AC1 = 0.830), though certain inclusion and exclusion criteria showed larger disagreement than others. Refining the inclusion and exclusion criteria slightly improved recall and made decisions easier for some LLMs, but overall impacts of criteria refinement were modest. LLMs are not yet ready to replace humans in paper screening and the advantages new, more costly models bring, appear to be very limited. Agent-based approaches, prompt engineering, and further criteria refinement are three potential future research avenues.