Zero-Shot Clinical Trial Patient Matching with LLMs
Open accessAbstract
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.).
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Many published trial-matching approaches remain retrospective, disease-limited, or optimized for text similarity and retrieval rather than auditable patient-trial execution over longitudinal records.
“many published approaches remain retrospective, disease-limited, or optimized for text similarity and retrieval rather than auditable patient–trial execution over longitudinal records.”
AI systems for clinical trial operations can parse biomarker requirements, prior therapies, and performance status from EHRs, identify potentially eligible patients, and flag candidates for screening.
“Systems parse biomarker requirements, prior therapies, and performance status from EHRs, identify potentially eligible patients, and flag candidates for screening [56,57,58,59,60,61,62].”
From Artificial Intelligence in Clinical Oncology: From Productivity Enhancement to Creative Discovery (2025) · cites this paper as [56]
One study reported a 30% reduction in initial report generation time with AI report drafting, though comprehensive evaluation including verification and correction time remains limited.
“One study reported a 30% reduction in initial report generation time, though comprehensive evaluation including verification and correction time by radiologists remains limited [56].”
From Artificial Intelligence in Clinical Oncology: From Productivity Enhancement to Creative Discovery (2025) · cites this paper as [56]
The citation lists haven’t been fetched yet
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
- Publisher
- Massachusetts Medical Society
- 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
- green
- arxiv.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review