NOT-NS-22-072- Notice of Intent to Publish a Funding Opportunity Announcement for Diagnostic Centers of Excellence (X01 Clinical Trial Not Allowed)

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Human Genome Research Institute (NHGRI)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Center for Advancing Translational Sciences (NCATS)

Established by the National Institutes of Health (NIH) Common Fund in 2013, the Undiagnosed Diseases Network (UDN) is a network of NIH intramural and extramural researchers and clinicians whose primary goals are to use team science to improve the diagnostic journey for patients with undiagnosed diseases and to catalyze research into unknown disease mechanisms. The UDN also aims to promote the use of genomics data in disease diagnosis and to share data and approaches widely throughout the scientific community. This highly successful Common Fund program will end in July 2023.

To have a broader impact on the clinical practice of undiagnosed diseases in the 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 diverse populations across the nation and foster scientific discovery. This Notice informs the research community that NIH intends to publish a Funding Opportunity Announcement (FOA) that solicits applications for the development of a Data Management and Coordinating Center (DMCC). The DMCC is intended to provide coordination, infrastructure, data management, and clinical research support for a new network of clinical sites. Sites across the US that provide expert diagnostic services for patients with undiagnosed diseases will be solicited to join a collaborative effort that is coordinated by the DMCC to promote diagnosis and 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 network will consist of the DMCC, highly qualified and collaborative clinical sites [designated Diagnostic Centers of Excellence (DCoEs) ], the Undiagnosed Diseases Program (UDP), participants with undiagnosed diseases, patient advocacy groups, the NIH, and other stakeholders including external funding or resource providers. A related Notice (NOT-NS-22-072) describes the application process and requirements for clinical sites to join the future network.

This FOA will use a cooperative agreement mechanism to fund one DMCC for 5 years (FY2023-2027) and is expected to be published in May 2022 with an application due date in July 2022. This Notice is being published now, in advance of the FOA, so that potential applicants have sufficient time to develop meaningful collaborations and responsive projects. Details of the planned FOA are provided below.

This Notice encourages applications with expertise in the clinical practice and research of rare and undiagnosed diseases, and strengths in the following areas: (1) leadership and project management of large, multi-site networks in rare and undiagnosed diseases; (2) building, analyzing and dissemination of diagnostic tools, bioinformatic and genomic technologies, and educational materials in rare and undiagnosed diseases; (3) developing and maintaining web- or cloud-based systems that allow for data management and sharing between multiple organizations; (4) medical genetics including informatics expertise in clinical genomics/metabolomics and gene function studies conducted in model systems designed to facilitate a participant’s diagnosis; (5) evaluation of network operations, (6) collaboration with and outreach to undiagnosed diseases patients and patient advocacy groups, and the broader undiagnosed diseases community; and (7) developing partnerships with clinical sites, third party payers, philanthropic organizations, for-profit and non-profit organizations that have interest in ending the diagnostic odyssey for patients with undiagnosed diseases.

The DMCC will provide leadership and assistance to the entire network through three cores:

1. Administrative Core, responsible for responding to the evolving needs of the network, including:

• governance, policy, oversight of all decision-making processes, and budget management;
• helping to manage a single IRB protocol (led by the UDP), and establishing a manual of operations;
• patient engagement, and improving participants experiences by incorporating the perspectives of undiagnosed participants and patient advocacy groups into network activities and decisions;
• developing and maintaining a public-facing portal that is equipped to receive applications to join the network from healthcare providers on behalf of undiagnosed participants;
• promoting collaborations between clinical and laboratory scientists both within and outside the network to facilitate participants diagnoses and advance new research discoveries;
• working with NIH program staff, network members and other stakeholders to identify and recruit highly qualified clinical sites to join the network with the goal of expanding the network into a nationwide resource that serves diverse patient populations;
• helping to build complementary relationships between the network and outside strategic funding and resource partners including: rare disease foundations and undiagnosed diseases patient advocacy groups; philanthropic organizations; third-party payers; 501(c)(3) organizations; industry partners; and other outside funding or resource providers.

2. Data Management Core, responsible for:

• establishing and maintaining efficient web/cloud-based data systems and repositories;
• developing the infrastructure necessary for timely collection, harmonization, quality control, storage, submission, sharing, and analysis of clinical research data obtained from network sites (includes data from UDN Phase I-II);
• providing statistical expertise and advice to network DCoEs and the UDP regarding optimal approaches to the analysis of network data;
• incorporating the use of Common Data Elements to facilitate broader and more effective use of data and advance research across studies.

3. Clinical Research Support Core, responsible for:

• assisting DCoEs and the UDP in the diagnosis of network participants by managing a Case Review Committee and other virtual consultation meetings;
• providing bioinformatics and other expertise (as personnel on grant and/or as ad hoc consultants) to aid network investigators in designing gene function studies in model organisms or cell-based systems and clinical genomics/metabolomics investigations as needed to facilitate a diagnosis;
• issuing small subawards to support: DCoE data sharing; or pilot research projects to facilitate a participant’s diagnosis and catalyze new research discoveries in undiagnosed diseases (e.g., through gene function, non-routine clinical genomics/metabolomics, immunologic, or exposome studies to be performed by DCoE investigators and their collaborators).

TBD