Rarely mentioned: how we arrived at the quantitative definition of a rare disease

Patients' difficulty obtaining medications for rare diseases and the advocacy of mothers led to a compelling and convoluted story of the development of the Orphan Drug Act (ODA) of 1983. While valid criticisms of the ODA remain, articles continue to be published on its ongoing beneficent influence. As hoped, ODA tax incentives stimulated research to develop pharmaceutical interventions for rare diseases. The initial ODA defined rare diseases qualitatively, but the 1984 Amendments established that <200,000 American citizens afflicted with a specific disease would be the numerical starting point. Considerable sleuthing was required to determine not only the source of this iconic number, but the reason this number was proposed. A coalition of Food and Drug Administration representatives, pharmaceutical executives, academic researchers, and members of rare disease advocacy organizations met in Washington, DC, and helped formulate the nuts and bolts of the ODA. As it turns out, two women at the conference brokered a deal in the restroom during a break and finalized this number. Paradoxically, rare diseases are not rare. Collectively, about 5000 to 7000 rare diseases are recognized and affect over 300,000 million people worldwide. Physicians should recognize that the collaboration of patient advocacy groups is an increasingly socially and politically effective force, bringing cohesion and recognition to associations such as the National Organization for Rare Disorders.