Natural History, Patient Registry, and Patient Voice

Rare disease drug development is complex due to the challenges of trial design with small populations, incomplete or unknown information about the natural history of the condition and the degree of unmet medical needs. The natural history studies and the patient’s voice are critical components to rare disease drug development. In recent years, there is also strong regulatory support to incorporate natural history and patient voice into rare disease drug development. Multi-stakeholders including dedicated patients, their caregivers and families, physicians, scientists, healthcare professionals, patient advocates, biopharmaceutical companies and regulatory agencies need to work together to advance the science to understand the disease and develop the better treatments to patients to resolve what matters to them the most. In this chapter, how the natural history studies can be designed, conducted, or leveraged is discussed. Various methods and considerations focusing on patient-focused drug development (PFDD), especially to the clinical outcome assessment (COA), are described in detail. Additionally, how electronic health records and digital technology play a role in natural history studies are discussed. One successful case example is illustrated incorporating natural history studies and/or patient voice into the drug development and led to a drug approval.