Successful drug development requires a comprehensive understanding of the underlying disease. To design reliable clinical trials with meaningful, measurable outcome measures, sponsors must apply thorough knowledge of disease presentation, manifestations, and progression, which may be challenging in rare diseases where this information is minimal. Thus, observational studies, encompassing both registry and natural history studies, play important roles in rare disease research. In fact, the value of prospectively designed, protocol-driven natural history studies initiated in the earliest stages of drug development planning cannot be overemphasized.
In this white paper, we discuss the challenges of rare disease development and explore the role of observational studies in informing clinical development, with an emphasis on natural history studies.