Setting up a DataSHIELD Hub for the German Medical Informatics Initiative: Challenges and Lessons Learned

The secondary use of clinical routine data offers major opportunities for biomedical research but also poses challenges regarding data protection, interoperability, and coordination. Within the German Medical Informatics Initiative (MII), Data Integration Centers (DICs) provide harmonized and secure access to routine data for research. To enable privacy-preserving multi-centric analyses without exchanging individual-level data, a federated DataSHIELD infrastructure was implemented for a study on the biomarker NT-proBNP in patients with atrial fibrillation. This paper presents its design, implementation, key challenges, and lessons learned, and derives recommendations for future deployments. Each site, selected based on availability of the required variables and operational readiness, provided standardized datasets via local Opal servers connected to a central hub. The setup enabled GDPR-compliant analyses across multiple hospitals but required substantial manual configuration and maintenance. Main challenges included version compatibility, limited analytical functionality, and the lack of automated deployment and testing. Addressing these issues calls for standardized installation workflows, improved version and access management, and modular extensions of functionality. Overall, the study demonstrates the feasibility of establishing a federated analysis infrastructure within the MII while also highlighting the need for more scalable and flexible solutions.