Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (UG3/UH3 Clinical Trial Not Allowed)

The purpose of this FOA is to fund research centers that will establish longitudinal cohorts in rare HLBS diseases to investigate unaddressed research questions using epidemiologic study designs and methods that are appropriate for conditions affecting fewer than 200,000 persons in the US. These observational cohort studies should be designed to provide an evidence base for future interventional studies, including clinical trials; for developing better diagnostics than those that are currently available; for answering early translational questions; or for broader implementation of guidelines for managing these diseases. This program will provide opportunities to advance rare disease research using genetics and deep phenotyping to characterize the disease and to identify disease sub-types; to use data science methods that integrate clinical and patient-reported outcomes (PROs) with laboratory, imaging, environmental and -omics data to understand the natural history of disease; to generate data that differentiate patients with the same morphological phenotype but different genetic mutations and severity of outcomes; to elucidate genotype-phenotype interactions and multisystem phenotyping to develop reliable and valid predictive tools to determine who will respond to which treatments and when to intervene; and to encourage innovative methods such as telemedicine to include participants with rare diseases located in remote locations. This initiative will allow applicants to study related rare diseases, disorders, conditions or syndromes together based on pathogenesis, affected biochemical, cellular or physiological features or organ system involvement. Studying related rare diseases within the same cohort could help understand the nuances, and knowledge gained from one disease and could accelerate the advances in related diseases. For example, investigators may propose to study hemoglobin disorders rather than only sickle cell anemia or thalassemia.