Towards AI-Assisted Clinical Trial Matching: Practical Considerations, Multicenter Evaluation, and Real-World Deployment
Authors: Yin Fang, Qiao Jin, Shubo Tian, Lauren He, Maya Geer, Noor Naffakh, Ryan Huu-Tuan Nguyen, Zifeng Wang, +19 more
Organizations: Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. · UI Health, University of Illinois Chicago. Chicago, IL, USA. · University of Illinois Urbana-Champaign, Urbana, IL, USA. · Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National2026 Institutes of Health, Bethesda, MD, USA. · Medical Oncology Service, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USASep · The Cholangiocarcinoma Foundation, Herriman, UT, USA. · Division of Cancer Sciences, University of Manchester, Manchester, UK. · Office of Patient Recruitment, NIH Clinical Center, Bethesda, MD, USA. · UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Clinical trials are essential for advancing cancer care and drug development, but many fail because of insufficient patient enrollment. While there is growing interest in using AI to support patient recruitment, existing systems largely perform eligibility assessment alone and have rarely been evaluated in real-world oncology workflows. Here we present TrialGPT 2.0, an AI-assisted clinical trial recommendation system designed for real-world deployment. Rather than asking only whether a patient may qualify, the system also assesses which trials warrant further consideration given the patient's current clinical needs and local workflow priorities, and provides structured, inspectable explanations for expert review. Importantly, we evaluated TrialGPT 2.0 retrospectively and prospectively across multiple oncology-focused settings, spanning government, academic cancer-center, patient-advocacy, and NIH referral workflows. In retrospective multicenter cohorts comprising 288 cases, TrialGPT 2.0 retrieved at least one clinician-recommended trial in its top 10 recommendations for approximately 91% of cases while reducing clinician screening time by 55.0%. In a six-month prospective evaluation embedded in an active precision oncology tumor board, TrialGPT 2.0 contributed additional trial opportunities missed by the routine workflow, expanding patient access to clinical trial participation by 90.9%. To support scientific reproducibility, we also introduce NIH-TrialBench, a clinician-authored dataset comprising 126 diverse synthetic patient vignettes and matching scenarios from 11 NIH Institutes and Centers. Together, these results support the value of AI to assist clinical trial matching by improving clinician efficiency and identifying frequently overlooked trial opportunities, ultimately helping to expand and accelerate accrual to cancer trials.
This paper examines records retrieved from the ClinicalTrials.gov registry to characterize temporal trends in AI terminology and the geographical distribution of AI trials. The work also reports on an exploratory hybrid human-AI approach to analyzing human-AI interaction trends in registered clinical trials. The hybrid workflow comprised a frontier generative AI model (GPT-5.5) and human review to screen and categorize records returned by an AI-focused search. The findings indicate a marked increase in AI-related trials over time, with recent growth in references to machine learning, deep learning, chatbots, GPTs, and large language models. Geographically, China and the United States accounted for the largest numbers of AI-related trials, with notable recent increases in several other countries including Italy, France, Spain, the UK and Turkey (Türkiye). In a random sample of 100 records, human and AI classifiers showed good agreement in identifying studies not substantively using AI, but lower agreement in classifying human-AI interaction, particularly where health professional interaction was ambiguous or insufficiently described. Overall, the results suggest that hybrid human-AI screening of clinical trial records is potentially viable, but clearer trial reporting and more precise interaction definitions will benefit the process.
Many real-world retrieval and matching problems require more than topical relevance: a candidate must satisfy the specific constraints of one profile among many, not just be relevant to it. Clinical trials are a high-stakes instance of this challenge: they are central to evidence-based medicine, yet many struggle to meet enrollment targets, despite the availability of over half a million trials listed on ClinicalTrials.gov, which attracts approximately two million users monthly. Existing retrieval techniques, largely based on keyword and embedding-similarity matching, treat eligibility constraints as soft signals rather than binding requirements, resulting in low recall, low precision, and limited interpretability. We propose SatIR, a scalable, efficient, high-precision, high-recall, interpretable clinical trial retrieval method based on formal constraint satisfaction. Leveraging established medical ontologies, we use Large Language Models (LLMs) to convert informal reasoning -- regarding ambiguity, implicit clinical assumptions, and incomplete patient records -- into explicit, precise, controllable, and interpretable formal Satisfiability Modulo Theories (SMT) constraints. For scalable and efficient retrieval, we project the SMT matching problem onto relational algebra, enabling an efficient database implementation that retains high recall while sacrificing little precision. SatIR consistently improves eligibility-aware retrieval over similarity-based baselines on the SIGIR 2016 dataset and a benchmark derived from TREC 2022. Relative to TrialGPT-style retrieval, SatIR retrieves 32%-72% more relevant-and-eligible trials per patient on SIGIR 2016 and achieves 1.8-3.2x higher eligible-trial recall on the TREC benchmark. Retrieval is fast, requiring only 146 milliseconds per patient over 3,621 SIGIR trials.
Artificial intelligence (AI) and natural language processing (NLP) are increasingly used to extract, integrate, and interpret biomedical knowledge relevant to cancer genomics, yet their translation into routine clinical oncology has been comparatively slow. The central challenge is not computational capability alone, but trustworthy integration into clinical workflows. This review examines how NLP and AI support the cancer genomics pipeline, from literature mining and automated variant interpretation to clinical trial matching, knowledge graph construction, and multimodal data integration. We identify four interrelated translational failure domains: evidence inconsistency, explainability and uncertainty, data governance and reproducibility, and interoperability. Rather than considering these challenges in isolation, we take a systems-level view, focusing on their interaction across the translational pathway. We propose a conceptual framework and roadmap for addressing these domains through rigorous validation, uncertainty-aware methods, interoperable infrastructures, regulatory alignment, and human oversight across the AI lifecycle. Progress toward routine clinical use will depend less on further improving model capability than on systematically addressing these interacting failure domains from development through deployment and post-deployment monitoring.