 The European Severe Asthma Clinical Research Collaboration, known as SHARP, Severe Heterogeneous Asthma Research Collaboration, patient-centered, has developed a blueprint for using real-world data from existing disease registries to conduct federated analyses. This blueprint includes organizational, financial, conceptual, technical, analytical, and research components. It addresses the challenges associated with harmonizing data from disparate sources, building a strong network of collaborators, and leveraging artificial intelligence and machine learning techniques. Ultimately, this blueprint provides a roadmap for other clinical research collaborations looking to leverage real-world data from existing disease registries. This article was authored by Johanna Say Crows, Aruna T. Bancel, Immanuel Barrett, and others.