In the USA, a rare disease is defined as one that affects no more than 200,000 individuals nationwide (a prevalence of roughly six per 10,000), and in Europe as one that affects five per 10 000, or around 250,000 individuals. Most current treatments are supportive rather than disease-modifying, leaving the majority of rare disease patients with considerable unmet medical needs.
The design and delivery of clinical trials in the rare disease arena bring specific considerations and potential pitfalls for researchers, patients, pharmaceutical companies, and regulators. Examples of trial-related questions/issues that need to be addressed include recruitment targets, dropout rates, and, ultimately, challenges of regulatory approval if the criteria for efficacy and safety are met.
As a requirement, most rare disease clinical trials are multicentre, and often multinational for sufficient patient recruitment, even in phase I and II trials. This can challenge clinical study protocol harmonization, the selection of appropriate biomarkers, ethical review, site IRB approval, indemnity, organization of clinical services, standards of care, and cultural diversity.