Currently, there are about 7,000-10,000 known rare diseases that affect people in the US, yet only a few hundred (less than 5%) have a treatment and even fewer a cure. A rare disease is defined in US law (Orphan Drug Act (ODA) of 1983, Rare Diseases Act (RDA) of 2002 ) as a disease or condition that affects fewer than 200,000 people in the US. Most rare diseases affect far fewer patients than this, with most rare diseases affecting only a few hundreds to thousands of patients. Collectively, however, rare diseases are not rare at all, and in total are estimated to affect as many as 25-30 million patients in the US, making rare diseases a large public health consideration. Given the large number of different rare diseases, each of which affects only a small number of patients, assessing the true impact of rare diseases on healthcare systems in the US is challenging. Many patients with rare diseases have difficulty obtaining a timely and accurate diagnosis (referred to as the diagnostic odyssey) and there is a lack of data regarding the likely and relatively large number of patients, who have not yet received a rare disease diagnosis. Additionally, International Classification of Disease (ICD) codes largely do not exist for many rare diseases (~50%), leading to myriad downstream effects including difficulty in identifying rare disease patients within healthcare systems databases, imprecise coding of patients under larger “umbrella” (e.g., developmental delay) or “not elsewhere classified (NEC)” terms, poor tracking within databases, and fiscal invisibility given their fragmentation under 1,000s of different terms. This is particularly problematic for (1) characterizing the clinical course of rare disease patients, (2) quantifying (and alleviating) the cost of medical care for people with rare diseases (by disease and in aggregate), (3) and identifying undiagnosed or misdiagnosed rare disease patients. In order to better assess the healthcare utilization, diagnostic journey and clinical course, and cost/utilization impacts of rare diseases on patients and healthcare systems, NCATS ORDR is undertaking pilot assessments in order to develop methods to more accurately identify rare disease patients and assess the impacts (utilization and cost) of rare diseases on healthcare systems by leveraging large health databases and analytics support. Such efforts to gather, quantify, and delineate the data behind rare disease patients will not only accumulate much-needed rare disease knowledge and help to identify research gaps, but will also advance both common and rare disease research, care, and segmentation associated with precision medicine. NCATS ORDR seeks to identify utilization patterns prior to accurate diagnosis and estimate costs of medical care during the diagnostic odyssey, with the larger goal of using this information to inform the development of approaches to diagnose and identify rare disease patients sooner, while improving overall patient c...