Increasing emphasis on rare diseases has led to a greater need to accurately define the profile, characteristics, and outcomes of patients living with those conditions. The development of safe and effective treatments of rare diseases requires a deep understanding of the disease of interest, including its frequency, clinical features, risk factors, outcomes, burden, and evolution. Unfortunately, for most rare diseases, this information may not be available. Observational studies — including both patient registries and natural history studies — help address this challenge by providing insight into not just the disease but also the endpoints and outcome measures that will be relevant and meaningful to patients and other key stakeholders in clinical trials.
Issues Faced in Rare Disease Development
In rare diseases, patient populations are inherently small and geographically dispersed. Due to the low incidence and prevalence of these conditions, diagnosis may be delayed, and data collection may be scarce, incomplete, or inconsistent. Understanding the disease is also complicated by:
- Disease heterogeneity, including multiple and atypical phenotypes
- Lack of clinical experience and expert guidelines
- Absence of validated methods for assessing disease-specific conditions
- Lack of natural history data
Observational studies play a critical role in filling these gaps in disease knowledge and informing the design of interventional studies to support successful drug development.
Observational Study Types
In clinical trials, patients receive interventions according to a pre-defined protocol with the objective of improving outcomes. In contrast, the overarching goal in observational studies is to observe natural relationships between disease characteristics and outcomes. Patients may receive but are not assigned to specific interventions.