Estimating the Prevalence of Rare Diseases: Long-Chain Fatty Acid Oxidation Disorders as an Illustrative Example

INTRODUCTION: Determining the epidemiology of disease is critical for multiple reasons, including to perform risk assessment, compare disease rates in varying populations, support diagnostic decisions, evaluate health care needs and disease burden, and determine the economic benefit of treatment. However, establishing epidemiological measures for rare diseases can be difficult owing to small patient populations, variable diagnostic techniques, and potential disease and diagnostic heterogeneity. To determine the epidemiology of rare diseases, investigators often develop estimation models to account for missing or unobtainable data, and to ensure that their findings are representative of their desired patient population. METHODS: A modeling methodology to estimate the prevalence of rare diseases in one such population—patients with long-chain fatty acid oxidation disorders (LC-FAOD)—as an illustrative example of its applicability. RESULTS: The proposed model begins with reliable source data from newborn screening reports and applies to them key modifiers. These modifiers include changes in population growth over time and variable standardization rates of LC-FAOD screening that lead to (1) a confirmed diagnosis and (2) improvements in standards of care and survival estimates relative to the general population. The model also makes necessary assumptions to allow the broad applicability of the estimation of LC-FAOD prevalence, including rates of diagnosed versus undiagnosed patients in the USA over time. CONCLUSIONS: Although each rare disease is unique, the approach described here and demonstrated in the estimation of LC-FAOD prevalence provides the necessary tools to calculate key epidemiological estimates useful in performing risk assessment analyses; comparing disease rates between different subgroups of people; supporting diagnostic decisions; planning health care needs; comparing disease burden, including cost; and determining the economic benefit of treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-022-02186-2.