Cited by 59Artificial Intelligence in Healthcare and EducationMachine Learning in HealthcareTopic Modeling

Zero-Shot Clinical Trial Patient Matching with LLMs

Open access
Wornow, Michael, Lozano, Alejandro, Dash, Dev, Jindal, Jenelle, Mahaffey, Kenneth W., Shah, Nigam H.·2025·NEJM AI

Abstract

AbstractMatching patients to clinical trials is a key challenge in bringing new drugs to market. Identifying patients who meet eligibility criteria for a trial is highly manual, taking up to 1 hour per patient. Automated screening is challenging, however, as it requires the ability to understand unstructured clinical text. To address this, we have designed a zero-shot large language model (LLM)-based system that evaluates a patient's medical history (as unstructured clinical text) against trial inclusion criteria (also specified as free text). We investigate different prompting strategies and design a novel two-stage retrieval pipeline to reduce the number of tokens processed by up to a third while sustaining high performance. Our contributions are threefold. First, we achieve state-of-the-art performance on the 2018 n2c2 cohort selection challenge, the largest public benchmark for clinical trial patient matching. Second, this system can improve the data and cost efficiency of matching patients an order of magnitude faster and more affordably than the status quo. Third, we demonstrate the interpretability of our system by generating natural language justifications for each eligibility decision, which clinicians found coherent in 97% of correct decisions and 75% of incorrect ones. These results establish the feasibility of using LLMs to accelerate clinical trial operations, with the zero-shot retrieval architecture scalable to arbitrary trials and patient record length with minimal reconfiguration. (Funded by the Clinical Excellence Research Center at Stanford Medicine and others.).

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Crossref · 10.1056/aics2400360

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References 16 · Cited by 59

Authors
Wornow, M., Lozano, A., Dash, D., Jindal, J., Mahaffey, K. W., & Shah, N. H.
Affiliations
Stanford University (US)
Venue
NEJM AI
Published
2025-01-01
Volume
2
Issue
1
Pages
AIcs2400360-AIcs2400360
ISSN
2836-9386 (ISSN-L)
OpenAlex
W4405736832
Cited by
59
References
16
Citations by year
2026: 22 · 2025: 31 · 2024: 6
FWCI
5.52
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • NEJM AI (publishedVersion)
  • PubMed (publishedVersion)
  • arXiv (Cornell University) (submittedVersion, cc-by)
  • arXiv (Cornell University) (cc-by)
Topics
  • Health Sciences › Medicine › Health Informatics › Artificial Intelligence in Healthcare and Education
  • Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
  • Physical Sciences › Computer Science › Artificial Intelligence › Topic Modeling
Keywords
zero-shot learning, large language models, patient recruitment, inclusion and exclusion criteria

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