eHealth systems, such as digital care applications or remote monitoring devices, can improve health outcomes using user-centered design principles to create medical devices that adapt to users’ needs and contexts. Data-enabled design (DED) builds on these principles by leveraging user-generated data to iteratively refine systems based on real-world use, enabling adaptive and context-sensitive solutions. However, its exploratory and iterative nature conflicts with the rigid protocols required in clinical trials to evaluate safety and effectiveness. This study revises DED in alignment with clinical trial requirements, identifying four key challenges and proposing a four-phase Clinical Data-Enabled Design (C-DED) framework. This framework reconciles exploratory design with trial methodological demands, supporting the development of safe, effective, and user-centered eHealth medical devices.