Zero-Shot Clinical Trial Patient Matching with LLMs
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Abstract (arXiv)
Matching patients to clinical trials is a key unsolved challenge in bringing new drugs to market. Today, identifying patients who meet a trial's eligibility criteria is highly manual, taking up to 1 hour per patient. Automated screening is challenging, however, as it requires understanding unstructured clinical text. Large language models (LLMs) offer a promising solution. In this work, we explore their application to trial matching. First, we design an LLM-based system which, given a patient's medical history as unstructured clinical text, evaluates whether that patient meets a set of inclusion criteria (also specified as free text). Our zero-shot system achieves state-of-the-art scores on the n2c2 2018 cohort selection benchmark. Second, we improve the data and cost efficiency of our method by identifying a prompting strategy which matches patients an order of magnitude faster and more cheaply than the status quo, and develop a two-stage retrieval pipeline that reduces the number of tokens processed by up to a third while retaining high performance. Third, we evaluate the interpretability of our system by having clinicians evaluate the natural language justifications generated by the LLM for each eligibility decision, and show that it can output coherent explanations for 97% of its correct decisions and 75% of its incorrect ones. Our results establish the feasibility of using LLMs to accelerate clinical trial operations.
Key facts. Cited by 35 papers in the map (data through 7 Oct 2026). Builds on 22 of its 56 references that are in the map. First posted on arXiv 5 Feb 2024.
Builds on
22 of 56 references.
References · 22
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- 2020COMPOSE: Cross-Modal Pseudo-Siamese Network for Patient Trial Matchingcited by 37
- 2023Scaling Clinical Trial Matching Using Large Language Models: A Case Study in Oncologycited by 24
- 2023Distilling Large Language Models for Matching Patients to Clinical Trialscited by 16
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Citing papers per year: 2024: 12; 2025: 14; 2026: 9.
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- 2025A Collection of Innovations in Medical AI for patient records in 2024cited by 7
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- 2024Automated Clinical Data Extraction with Knowledge Conditioned LLMscited by 5
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- 2025LLM-Match: An Open-Sourced Patient Matching Model Based on Large Language Models and Retrieval-Augmented Generationcited by 2
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- 2026Are Multimodal LLMs Ready for Clinical Dermatology? A Real-World Evaluation in Dermatologycited by 1
- 2025Am I eligible? Natural Language Inference for Clinical Trial Patient Recruitment: the Patient's Point of Viewcited by 0
- 2025Initial Investigation of LLM-Assisted Development of Rule-Based Clinical NLP Systemcited by 0
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- 2026Extracting Breast Cancer Phenotypes from Clinical Notes: Comparing LLMs with Classical Ontology Methodscited by 0
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- 2026Towards AI-Assisted Clinical Trial Matching: Practical Considerations, Multicenter Evaluation, and Real-World Deploymentcited by 0
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- 2026Ten Headache Specialists versus Artificial Intelligence for Clinical Literature Summarization: A Critical Evaluation and Comparison3 Jun 2026
- 2026Are Multimodal LLMs Ready for Clinical Dermatology? A Real-World Evaluation in Dermatology1 May 2026
- 2026Eligibility-Aware Evidence Synthesis: An Agentic Framework for Clinical Trial Meta-Analysis3 Apr 2026
- 2026Extracting Breast Cancer Phenotypes from Clinical Notes: Comparing LLMs with Classical Ontology Methods16 Mar 2026
- 2026Med-V1: Small Language Models for Zero-shot and Scalable Biomedical Evidence Attribution5 Mar 2026
- 2026Medical Triage as Pairwise Ranking: A Benchmark for Urgency in Patient Portal Messages19 Jan 2026
- 2025DiscoVerse: Multi-Agent Pharmaceutical Co-Scientist for Traceable Drug Discovery and Reverse Translation23 Nov 2025
- 2025AI-assisted workflow enables rapid, high-fidelity breast cancer clinical trial eligibility prescreening7 Nov 2025
- 2025A systematic review of trial-matching pipelines using large language models13 Sep 2025
23 more
- 2025Initial Investigation of LLM-Assisted Development of Rule-Based Clinical NLP System19 Jun 2025
- 2025A Survey on LLM-Assisted Clinical Trial Recruitment18 Jun 2025
- 2025Developing Large Language Models for Clinical Research Using One Million Clinical Trials22 May 2025
- 2025Comparing representations of long clinical texts for the task of patient note-identification31 Mar 2025
- 2025Am I eligible? Natural Language Inference for Clinical Trial Patient Recruitment: the Patient's Point of View19 Mar 2025
- 2025Real-world validation of a multimodal LLM-powered pipeline for High-Accuracy Clinical Trial Patient Matching leveraging EHR data19 Mar 2025
- 2025LLM-Match: An Open-Sourced Patient Matching Model Based on Large Language Models and Retrieval-Augmented Generation17 Mar 2025
- 2025A Collection of Innovations in Medical AI for patient records in 202425 Feb 2025
- 2025Embedding-Driven Diversity Sampling to Improve Few-Shot Synthetic Data Generation20 Jan 2025
- 2025Clinical trial cohort selection using Large Language Models on n2c2 Challenges19 Jan 2025
- 2025BIOMEDICA: An Open Biomedical Image-Caption Archive, Dataset, and Vision-Language Models Derived from Scientific Literature13 Jan 2025
- 2024Generative AI in Medicine13 Dec 2024
- 2024A Perspective for Adapting Generalist AI to Specialized Medical AI Applications and Their Challenges28 Oct 2024
- 2024Entry-level guide to the use of large language models for medical research24 Oct 2024
- 2024iText2KG: Incremental Knowledge Graphs Construction Using Large Language Models5 Sep 2024
- 2024Improving Retrieval-Augmented Generation in Medicine with Iterative Follow-up Questions1 Aug 2024
- 2024Automated Clinical Data Extraction with Knowledge Conditioned LLMs26 Jun 2024
- 2024MedCalc-Bench: Evaluating Large Language Models for Medical Calculations17 Jun 2024
- 2024BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments27 May 2024
- 2024MultiCast: Zero-Shot Multivariate Time Series Forecasting Using LLMs23 May 2024
- 2024Advancing Multimodal Medical Capabilities of Gemini6 May 2024
- 2024PRISM: Patient Records Interpretation for Semantic Clinical Trial Matching using Large Language Models23 Apr 2024
- 2024ClinicalMamba: A Generative Clinical Language Model on Longitudinal Clinical Notes9 Mar 2024
- 2024Advancing Multimodal Medical Capabilities of Geminicited by 88
- 2024MedCalc-Bench: Evaluating Large Language Models for Medical Calculationscited by 64
- 2024ClinicalMamba: A Generative Clinical Language Model on Longitudinal Clinical Notescited by 22
- 2024iText2KG: Incremental Knowledge Graphs Construction Using Large Language Modelscited by 11
- 2024A Perspective for Adapting Generalist AI to Specialized Medical AI Applications and Their Challengescited by 8
- 2025A Collection of Innovations in Medical AI for patient records in 2024cited by 7
- 2024MultiCast: Zero-Shot Multivariate Time Series Forecasting Using LLMscited by 6
- 2024Automated Clinical Data Extraction with Knowledge Conditioned LLMscited by 5
- 2024PRISM: Patient Records Interpretation for Semantic Clinical Trial Matching using Large Language Modelscited by 4
- 2026Medical Triage as Pairwise Ranking: A Benchmark for Urgency in Patient Portal Messagescited by 3
- 2025Clinical trial cohort selection using Large Language Models on n2c2 Challengescited by 2
- 2025Real-world validation of a multimodal LLM-powered pipeline for High-Accuracy Clinical Trial Patient Matching leveraging EHR datacited by 2
12 most cited of 29 All 29 (JSON)
- 2026TrialAtlas: Multi-Agent Research Organization for Clinical Trial Design and Optimization18 Sep 2026
- 2026A primer on evaluation methods for large language models in healthcare13 Sep 2026
- 2026Towards AI-Assisted Clinical Trial Matching: Practical Considerations, Multicenter Evaluation, and Real-World Deployment1 Sep 2026
- 2026Ten Headache Specialists versus Artificial Intelligence for Clinical Literature Summarization: A Critical Evaluation and Comparison3 Jun 2026
- 2026Are Multimodal LLMs Ready for Clinical Dermatology? A Real-World Evaluation in Dermatology1 May 2026
- 2026Eligibility-Aware Evidence Synthesis: An Agentic Framework for Clinical Trial Meta-Analysis3 Apr 2026
- 2026Extracting Breast Cancer Phenotypes from Clinical Notes: Comparing LLMs with Classical Ontology Methods16 Mar 2026
- 2026Med-V1: Small Language Models for Zero-shot and Scalable Biomedical Evidence Attribution5 Mar 2026
- 2026Medical Triage as Pairwise Ranking: A Benchmark for Urgency in Patient Portal Messages19 Jan 2026
- 2025DiscoVerse: Multi-Agent Pharmaceutical Co-Scientist for Traceable Drug Discovery and Reverse Translation23 Nov 2025
- 2025AI-assisted workflow enables rapid, high-fidelity breast cancer clinical trial eligibility prescreening7 Nov 2025
- 2025A systematic review of trial-matching pipelines using large language models13 Sep 2025
12 newest of 29 All 29 (JSON)