VirtualTrialHarness: Coordinating Agentic Operationalization of Virtual Trial Protocols Across Complex Clinical Schemas

Pengze Li, Jingna Feng, Yue Yu, Yining Wu, Xinyue Hu +3

Virtual trials use routinely collected clinical data to evaluate treatment strategies, but translating a study protocol into an executable analysis requires determining how clinical concepts and study requirements should be represented in the available data and applied consistently across the workflow. These decisions depend on local data representations and operational conventions and can involve source selection, patient and encounter identity, linkage, and temporal interpretation. Here we introduce VirtualTrialHarness (VTHarness), an agent framework that coordinates virtual-trial operationalization by selecting reusable procedural skills for each workflow stage and uses explicit contracts to maintain consistent study decisions across stages. We also introduce VTBenchmark for evaluating source selection and cohort construction. Across three complex synthetic environments, VTHarness successfully produced all required cohort outputs matching the references in 95.1% of workflows after requirement clarification, compared with 60.4% using retrieval from the same procedural corpus. Procedural skills improved source recovery across three language models and increased source overlap…