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

Rare disease experts Groft and Posada-de-la-Paz pointed out in a recent book on rare diseases: The future presents considerable optimism for the rare diseases community. At the heart of this optimism is data and information gathered from well-constructed patient registries. The most recent figures from the Genetic and Rare Diseases Information Center supported by the ORDR [Office of Rare Diseases Research]/NCATS [National Center for Advancing Translational Sciences] and NHGRI [National Human Genome Research Institute] reveal that information has been made available for over 6800 rare and genetic diseases to requests from 120 countries in their fourteen-year history. The proposed International Classification of Diseases-11 , from the World Health Organization, provides the opportunity to increase the number of Rare Diseases with specific classification codes to approximately 5400 in their nomenclature. 18 Defining rare disease quantitatively by prevalence continues to be the most valid and abiding method for the rare disease community. If a better way exists, an international consortium of rare disease experts and statisticians would need to convene and arbitrate. Qualitative definitions may provide nuanced narrative augmentation that promotes discussion in the rare disease community, thus enhancing the sociopolitical agenda. Prevalence allows better comparison from country to country and other jurisdictions. Sociologists studying rare diseases have noted that the “prevalence-based definition of the categories of rare disease, by allowing distinct and co-ordinated uses, displays the features of a boundary object in this new setting.” This approach may act for the patients as a “political tool to express their needs, in vivid connection with their illness experience.” 16 The quantitative definition of rare disease originated in the 1984 Amendments to the Orphan Rare Drug Act of 1983. Through the efforts of consumer advocate Abbey Meyers, later a contributing founder of NORD, the figure of <200,000 people in the United States suffering from a particular disease legislatively emerged. Marion Finkel, MD, an FDA official, had proposed a number of 100,000 (an incidence rate of 0.05%), based on the notion that such a value was the upper limit of profitability for the pharmaceutical industry. In her official position with the FDA, Finkel, a determined catalyst and mediator, provided the glue that coalesced the FDA, the pharmaceutical industry, and patient advocacy groups to the abundant advantage of the rare disease community. Ultimately, the final answer was market driven but successful. Likely using financial data derived from available drugs for low prevalence diseases, Finkel constructed an economic model to arrive at this number. Carolyn H. Asbury, PhD, an expert in the philanthropy of rare diseases, spoke to the economic issues involved in this complex arena: Namely that orphan drugs have profiles of specific characteristics (patentability, development difficulties, availability of other drugs for the same use, for example) which have predictiveness as to whether the drug will obtain industry sponsorship, and if so, whether it will reach the market. This information has been imparted to the stakeholders involved in the planning process to help focus the issues. 19 Fortunately, the question of what prevalence number defines rare diseases seems to have been resolved, in the ladies’ lounge, by the rarely sung heroes of rare diseases, Marion Finkel and Abbey Meyers, among others.