Figure 1.

Flow diagram showing the process by which patients are accepted into and evaluated for a diagnosis within the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP). The process is divided into five major components listed along the left side. The initial component is patient selection. This is followed by patient admission to the NIH clinical research center (CRC) for phenotyping and, when appropriate, agnostic screening for disturbances of evolutionary, developmental, and biochemical homeostases. These data are then integrated computationally and through discussion to determine if there is a known medical diagnosis. Patients with a diagnosis are given disposition recommendations based on that diagnosis. For those without a diagnosis and without a candidate cause, their data are queued for iterative reanalysis, and they and their referring physician are given disposition recommendations based on what was learned. For those without a diagnosis and with a candidate cause, their data are subjected, as resources allow, to research studies to evaluate the potential causality, and they and their referring physician are given disposition recommendations based on what was learned.