Benchmarking and developing large language models using one million clinical trials

Abstract Developing artificial intelligence (AI) for clinical research requires a comprehensive data foundation for model benchmarking and development. Here, we introduce , a large-scale structured resource aggregating 1.6M clinical trial records from fifteen global registries linked with biomedical ontologies and literature. Using this resource, we construct 152K training and testing samples spanning eight clinical research tasks, including systematic review, trial design, and trial optimization. Benchmarking cutting-edge large language models (LLMs) reveals limited clinical reasoning capability in generic LLMs. In contrast, an 8B LLM developed on using supervised fine-tuning and reinforcement learning outperforms 70B generic counterparts across all eight tasks, with relative improvements of 73.7, 67.6, 38.4, 37.8, 26.5, 20.7, 20.0, 18.1, and 5.2%, respectively. These results demonstrate the potential of domain-adapted AI to improve evidence synthesis and clinical trial design, establishing as a foundation for scaling AI in clinical research.