Real-world evidence (RWE) has been used to improve quality of care, accelerate innovation, and evaluate emerging therapies for drugs, devices, and biologics. The Coordinated Registry Network (CRN), aggregating and linking highly curated patient data, has emerged as a model for RWE generation that has guided the development of the ASH Research Collaborative® (ASH RC) Data Hub. With the aim of bolstering research, enhancing clinical care, and expediting evidence generation using RWE, ASH RC, and the Innovative Genomics Institute (IGI) launched a joint initiative, “Accelerating Innovations for Sickle Cell Disease (SCD) with Real-World Evidence,” to evaluate and make recommendations to the Data Hub.