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LLM-assisted systematic review of large language models in clinical medicine

Sully F. Chen, Anton Alyakin, Andreas Seas, Eunice Yang, Jinhyuk Choi, Jin Vivian Lee, Amelia L. Chen, Pranav I Warman, Rochelle Bitolas, Robert Steele, Daniel A. Alber, Eric K. Oermann

2026Nature Medicine26 citationsDOIOpen Access PDF

Abstract

Clinical evaluations of large language models (LLMs) have rapidly expanded since 2022, yet their evidence base remains opaque. The overwhelming volume of studies creates challenges for manual curation and review. However, LLMs themselves offer the scalability and capability to evaluate the ever-growing evidence base. This LLM-assisted review identified 4,609 peer-reviewed studies in clinical medicine between January 2022 and September 2025, equating to roughly 3.2 papers per day. Only 1,048 studies used real-world patient data and of these only 19 were prospective randomized trials; most addressed simulated scenarios (n = 1,857) or exam-style tasks (n = 1,704). ChatGPT and related OpenAI models constitute 65.7% of evaluated models, with Gemini/Bard a distant second constituting 13.1% of evaluated models. Patient-facing communication and education comprised 17% of tasks, followed by knowledge retrieval, and education and assessment simulation. Across 1,046 head-to-head comparisons, LLMs outperformed humans in 33% of comparisons, with a strong dependency on task realism and level of training. At least 25% of studies had sample sizes less than 30. Despite the growth of LLMs in medicine, rigorous, patient-centered evidence remains scarce, underscoring the need for larger prospective trials before clinical adoption.

Topics & Concepts

MEDLINETask (project management)Clinical trialAlternative medicineMedicineEquatingEvidence-based medicineMedical educationPsychologyRandomized controlled trialScale (ratio)Sample (material)Knowledge baseFamily medicineClinical PracticeClinical study designDependency (UML)RealismPrecision medicineClinical decision makingReadabilityEnglish languageSystematic reviewData sciencePersonalized medicineComputer scienceCognitive psychologySample size determinationResearch designArtificial Intelligence in Healthcare and EducationMachine Learning in HealthcareGenomics and Rare Diseases
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