NIH – Data Management Coordinating Center for Diagnostic Centers of Excellence (U2C Clinical Trial Not Allowed)

June 17, 2022 by


This Funding Opportunity Announcement (FOA) solicits applications for a Data Management and Coordinating Center (DMCC) to provide infrastructure, data management, and clinical research support for a new network of clinical sites that provide diagnostic services for undiagnosed diseases. The new Network is intended to sustain some of the key research activities currently performed by the Undiagnosed Diseases Network (UDN), an NIH Common Fund program that was established in 2013 and will sunset in 2023. The DMCC will coordinate clinical sites that apply to join the new Network beginning in FY2023 as Diagnostic Centers of Excellence (DCoEs) through a related Resource Access Program (X01) or other NIH funding mechanisms. The DMCC will support the DCoEs and the NIH intramural Undiagnosed Diseases Program (UDP) by coordinating trans-network research activities, with services managed across three Cores: 1) Administrative Core; 2) Data Management Core, and 3) Clinical Research Support Core.


Undiagnosed diseases are defined as long-standing symptoms or elusive medical conditions that have not been diagnosed despite extensive clinical evaluation. Undiagnosed diseases are often due to rare conditions and can include: 1) not recognized, previously described diseases due to very low incidence or prevalence; 2) yet-to-be-described disorders; and 3) rare variations of more common diseases. These conditions present difficult problems for patients, their families, and physicians resulting in a high emotional, physical, and financial burden to patients who may spend many years seeking a diagnosis and path to treatment. Diagnoses in these difficult cases require teams of clinicians and scientists with a wide variety of special expertise. Scientific advances springing from these diagnoses require an organized approach to testing, data analysis, and validation in patients with similar rare conditions or in model organisms.

In 2008, the NIH established an intramural Undiagnosed Diseases Program (UDP) to aid individuals plagued by longstanding medical conditions that elude medical diagnosis. Using a team science approach, comprehensive clinical phenotyping and cutting-edge diagnostic and genomic technologies, the UDP was successful in ending the “diagnostic odyssey” for many individuals with rare, challenging, and difficult-to-diagnose diseases. Based on the success of the UDP, the NIH Common Fund announced in 2012 an expansion of the UDP to form a nation-wide network – the Undiagnosed Diseases Network (UDN) – composed of the NIH UDP and extramural Clinical Sites. Phase I (FY2013-2017) of the UDN included seven Clinical Sites including the UDP, a Coordinating Center, and Core Laboratories to facilitate diagnoses (genome sequencing, testing variants in model organisms, metabolomics, and a biorepository). In Phase II (FY2018-2022), the number of Clinical Sites was expanded to twelve. Since the launch of Phase I, the UDN has been very successful in achieving its objectives by: providing over 500 diagnoses; discovering hundreds of novel disease-associated genes and genomic variants, including new diseases and syndromes; and building an international reputation for establishing exemplary clinical practices, standards, and pipelines for genomics-based diagnoses.

In Phase II, the network was tasked to develop a framework that would continue the mission of the UDN after NIH Common Fund support ends in 2023. To have a broader impact on the clinical practice of undiagnosed diseases in the United States (US), the NIH envisions the UDN evolving into a larger, self-sustained network that, with public and private partners, can provide expert diagnostic services for undiagnosed patients across the nation and foster scientific discovery. Participating NIH Institutes and Centers intend to support a Data Management and Coordinating Center (DMCC) that will provide infrastructure and research support for a new network (henceforth referred to as the “Network” in this FOA) of clinical sites, designated “Diagnostic Centers of Excellence (DCoEs)” and the UDP. Sites across the US that provide expert diagnostic services for undiagnosed diseases will be solicited to join a collaborative effort that is coordinated by the DMCC to promote the discovery of new disease-associated genes and genomic variants, immunologic and metabolic abnormalities, as well as environmental insults that are causative in previously undiagnosed patients. In this new model, the new Network will consist of the DMCC, the UDP, highly qualified and collaborative DCoEs, patients with undiagnosed diseases (referred to as “participants” in this FOA), patient advocacy groups, and the NIH and other stakeholders including external funding providers and/or resource providers (e.g., Cores). A DCoE is defined as one or more clinical sites within the US that are willing to submit their most challenging, unsolved diagnostic cases for acceptance into the Network, and participate in the evaluation by the Network’s virtual consultation committees. DCoEs will have access to DMCC resources and infrastructure including access to high-quality phenotypic and genotypic data and collaboration with highly skilled physicians, researchers, and bioinformaticians. In FY2023, through a future RFA, clinical sites will be invited to join the Network by applying for an NIH X01 Resource Access Program award (or other NIH funding mechanisms) and will be selected amongst the respondents. Since DCoEs will not receive direct NIH funds through the X01 mechanism, DCoEs must have the appropriate infrastructure, expertise, and independent resources required to evaluate participants and conduct DNA sequencing and other specialized testing as needed. To qualify as a DCoE, each site will be expected to enroll a minimum of 5 participants per year, although some sites may have the capacity to enroll more participants. Initially, we expect that the DMCC will be coordinating the activities of at least 10-15 DCoEs, depending on the number of qualified X01 applications submitted to the NIH. However, NIH’s long-term vision is to see the Network expand to include DCoEs across the US in order to provide expert diagnostics services to diverse undiagnosed patient populations and, through strategic partnerships with patient advocacy groups and other stakeholders, to make important scientific discoveries while improving clinical practice for undiagnosed patients.

Key Dates:

Open Date (Earliest Submission Date): July 10, 2022
Letter of Intent Due Date(s): 30 days prior to the application due date
Applications Due: August 10, 2020

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Filed Under: Funding Opportunities