Clinical Trial Readiness for Rare Diseases, Disorders, and Syndromes (R21 Clinical Trial Not Allowed)

The Department of Health and Human Services through the National Institutes of Health has released the funding opportunity titled Clinical Trial Readiness for Rare Diseases, Disorders, and Syndromes (R21 Clinical Trial Not Allowed), under funding opportunity number PAR-25-450. This program is administered by the National Center for Advancing Translational Sciences and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. It is designed to support projects that address critical needs in preparing rare disease research for clinical trials, specifically by developing and validating biomarkers and clinical outcome assessment measures or by advancing understanding of the natural history of rare diseases. This initiative aims to improve the likelihood of success for upcoming clinical trials by filling essential gaps in trial readiness. Rare diseases affect fewer than 200,000 individuals in the United States, and many of them have no effective treatment options. Most are life-threatening or severely debilitating, with a majority impacting children. Despite scientific advances, only about five percent of rare diseases currently have approved therapies. This program acknowledges the need for validated tools, data, and methods to support rigorous clinical trials, which remain a key barrier to advancing therapeutic development. Projects funded under this notice are not clinical trials themselves but must focus on building the readiness necessary to design and implement such trials. The scope of work supported includes validation of biomarkers and clinical outcome measures, studies defining disease presentation and course relevant to clinical trial design, and ancillary studies leveraging ongoing clinical or longitudinal research. Applications must demonstrate sufficient clinical expertise, access to patient populations, and clear plans to address critical barriers to trial readiness. Proposals must be distinct from R01-level projects and are expected to leverage existing clinical research networks, collaborations with patient groups, and established data standards and tools. Projects that simply maintain registries, focus on biomarker discovery without validation, or propose direct therapeutic trials will be considered non-responsive. Awards will be made under the R21 mechanism with a project period of up to two years. Applicants may request up to $275,000 in direct costs for the total project, with no more than $200,000 in any single year. The number of awards will depend on the availability of appropriations and the quality of applications received. NIH grants policies apply, and pre-award costs are allowable as per NIH guidelines. Applications will undergo peer review based on importance of research, rigor and feasibility, and expertise and resources available to conduct the proposed work. Human subject protections, vertebrate animal use, biohazards, and budget justifications will be considered as additional review criteria where applicable. Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local governments, state governments, tribal governments, special districts, public housing authorities, independent school districts, and certain community-based organizations. Foreign organizations are not eligible, though non-U.S. components of U.S. organizations may participate. Individuals with the requisite expertise are encouraged to apply as principal investigators, provided they hold or can obtain the required eRA Commons registration. No cost sharing is required for this program. Applications open on January 17, 2026, with the first due date on February 18, 2026. Additional deadlines follow on a recurring schedule, with June and February submission dates through 2028. Applications are due by 5:00 PM local time of the applicant organization, and the program expires on July 21, 2028. Scientific review occurs within the same year, followed by council review and earliest start dates approximately six months after application. All applications must b

Submit early to allow for corrections, ensure compliance with NIH Research Instructions, and include letters of support when leveraging existing networks or ancillary studies