Background The exponential growth of electronic health records (EHRs), together with the recent entry into force of the European Health Data Space (EHDS) Regulation, highlights the urgent need for secure, interoperable environments that support the secondary use of health data. In response, HealthData@MAD-R (2) the design of a secure, interoperable technological architecture with federated capabilities based on international standards (DAMA and OMOP); and (3) the implementation of 4 use cases—optimizing rheumatology referrals, characterizing care pathways for long-term survivors of breast cancer, predicting unplanned hospitalizations, and evaluating the effectiveness of statins in older adults—to validate the data space while addressing diverse clinical and policy challenges. Together, these components demonstrate the potential of regional data spaces to support evidence-based clinical practice and public policy. Conclusions HealthData@MAD-R&I seeks to strengthen Madrid’s role in digital health innovation and contribute to the broader European health data ecosystem by promoting interoperable, privacy-compliant secondary use of health data. The project’s evaluation framework includes indicators for data quality, research outputs, and health care system impact. International Registered Report Identifier (IRRID) DERR1-10.2196/82815
León-García et al. (2026) studied this question.