Clinical trial recruitment is hindered by slow, costly, and labor-intensive processes, particularly due to the complexity of eligibility criteria often written in free text. This systematic review examines the use of large language models (LLMs) for matching clinical trial eligibility criteria to electronic health records (EHR). It evaluates zero-shot, few-shot, and fine-tuned LLM approaches, comparing their strengths, limitations, and deployment readiness in supporting patient-trial matching. Thirty-three studies published from 2017 to 2026 were included, with findings showing that zero-shot prompting is most adaptable for simple criteria, few-shot prompting offers consistent reasoning for ambiguous criteria, and fine-tuned models excel in task-specific performance but require labeled data and are less portable. The review concludes that no single approach is optimal for all trial screening tasks, and hybrid workflows combining various methods with human verification are most suitable for clinical use.
Clinical Intelligence Research Press