Description

The National Center for Advancing Translational Sciences (NCATS) intends to re-issue the Notice of Funding Opportunity (NOFO) Rare Diseases Clinical Research Consortia (RDCRC) for the Rare Diseases Clinical Research Network (RDCRN) (U54 Clinical Trial Optional)PAR-24-206to solicit applications for research to advance the diagnosis, management, and treatment of rare diseases. Each Rare Diseases Clinical Research Consortium (RDCRC) will promote highly collaborative, multi-site, patient-centric, translational, and clinical research. It is strongly encouraged that the RDCRC study outcome measures include those that address unmet clinical trial readiness needs that will move the field of research forward from its current state.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The NOFO is expected to be published in May 2025, with expected application due dates in June 2025 and the fall of 2025. This NOFO will utilize the U54 activity code, which supports specialized centers through multi-project cooperative agreement awards to support research activities with substantial involvement from NIH program staff. Details of the planned NOFO are provided below.

Research Initiative Details

The Rare Diseases Clinical Research Network (RDCRN) is a cooperative network composed of multiple Rare Diseases Clinical Research Consortia (RDCRC) and a Data Management and Coordinating Center (DMCC) to facilitate clinical research in rare diseases carried out by the RDCRCs.

Each RDCRC must propose to focus on at least three different rare diseases, defined as:

• Disorders - abnormal physical or mental conditions or ailments
• Syndromes - group of symptoms that occur together, or a condition characterized by a set of associated symptoms
• Diseases - a disorder of structure or function that effects a specific location and is not simply a result of physical injury
• Manifestations - symptom or sign of an ailment
• Conditions a particular state of being that limits/restricts something else

Each RDCRC must propose at least two clinical research projects, but no more than four. One clinical research project must be a longitudinal study. Options for additional clinical research projects include, but are not restricted to, natural history studies, biomarker studies and other clinical trials readiness studies. Knowledge from such clinical studies should be essential to direct subsequent clinical trials and can be invaluable for the targeted rare diseases.

The use of animal models is not permitted and will not be supported.

Clinical research, as it is defined by the NIH consists of:

1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. It includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies; or

2) Epidemiological and behavioral studies or;

3) Outcomes research and health services research.

Studies based entirely on publicly available or deidentified data or specimens (thus falling under45 CFR 46.101(b), Exemption 4) are not considered clinical research by this definition.

One of the Clinical Research Projects must be longitudinal in nature (e.g., natural history studies). Clinical research supported under this NOFO includes mechanistic studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention.

Projects must be focused only on rare diseases. In this document, a rare disease is defined as one that affects fewer than 200,000 people in the United States, as defined in the Rare Diseases Act of 2002.

Any interventional clinical trials proposed as part of a RDCRC must be Phase I, or early-stage proof-of-concept trials.

Areas of research can include, but are not limited to, the following:

• Clinical studies aimed at clinical trial preparation, including natural history studies
• Early-stage clinical trials
• Biomarkers
• Development of patient reported outcome measures
• Genotype/Phenotype studies
• Mechanistic trials/target engagement trials
• Diagnostic studies
• New treatment modalities
• Repurposing of drugs
• Prevention studies
• Newborn Screening, including conditions that are on the Recommended Uniform Screening Panel or have the potential to be added to it
• Patient-centered outcome measures

Patient and stakeholder experiences, perspectives, needs and priorities must be meaningfully incorporated into decisions and activities of the RDCRC.

The research problems proposed should require substantial collaborative efforts to solve, and thus are best carried out in a multi-site RDCRC setting. Applicants are encouraged to emphasize new ideas, novel approaches, and state-of-the-art technologies to address the needs for effective treatments and other strategies to improve the lives of individuals with rare diseases.

Applications must include multidisciplinary collaborative efforts, those involving patients, clinicians, researchers, bioinformaticians and others with appropriate expertise, along with stakeholders.

RDCRC applicants must also propose resource development, career enhancement and outreach activities that will enhance rare diseases research on a national and/or international level.

Consortia with research agendas at varying stages of scientific development within the research program are encouraged to apply. Early-stage consortia with many knowledge gaps that need to be addressed (e.g., groups that do not yet have established registries, groups with poorly defined natural history that would benefit from a RDCRC effort) are encouraged to apply.

When the NOFO is published specific areas of interests for the participating NIH Institutes will be indicated.