ProCARE: Real-World Study Automation via Profile-Grounded Evidence Contracts

Real-world studies (RWS) analyze routinely collected healthcare data, such as electronic health records and insurance claims, to estimate treatment effects, monitor safety, and identify risk factors outside randomized trials. Automating RWS with large language model agents is appealing but brittle: valid analyses depend on dataset-specific clinical semantics, including index dates, follow-up windows, patient/event-level units, and outcome boundaries that are often implicit in observational data. This leads to schema mismatches, temporal errors, inconsistent analytical granularity, and unsupported clinical claims. We present ProCARE, a profile-grounded framework that reformulates RWS automation as constrained compilation. ProCARE converts heterogeneous data profiles into Evidence Contracts specifying available variables, temporal attributes, distributions, and evidentiary limits, and compiles study objectives into RWS-IR, a strongly typed intermediate representation for variables, time relations, analysis units, and statistical tasks. Deterministic validation and localized repair then check and revise generated workflows across schema mapping, cohort construction, variable derivation, analysis, and interpretation. On 36 EHR-based benchmark tasks, ProCARE outperforms strong LLM-agent baselines in code executability, semantic consistency, and conclusion traceability, with automated violation diagnoses showing moderate-to-substantial agreement with blinded expert review. Code, benchmark prompts, evaluation scripts, and the fully de-identified HCC benchmark tables are publicly available at https://anonymous.4open.science/r/ProCARE-7E52.