Development of Biomarkers or Composite Biomarkers for Neurological and Neuromuscular Disorders (R61/R33 - Clinical Trial Optional) | PAR 25 024

Opportunity Information: Apply for PAR 25 024

The NIH funding opportunity PAR-25-024, titled "Development of Biomarkers or Composite Biomarkers for Neurological and Neuromuscular Disorders (R61/R33 - Clinical Trial Optional)," is designed to speed up the early pipeline of biomarker development for disorders of the nervous system and neuromuscular system. The central aim is to support projects that discover promising biomarkers and biomarker signatures (including composite biomarkers that combine multiple measures) and then carry out the initial rounds of evaluation needed to determine whether those candidates are strong enough to move into larger, definitive validation studies. In practical terms, NIH is looking for tools that can help neurotherapeutic development run more efficiently and, ultimately, support real clinical decision-making, such as diagnosis, patient stratification, prognosis, disease monitoring, or treatment response assessment.

This FOA emphasizes not just finding a potential biomarker, but also doing the early work that makes a biomarker credible and usable. Applicants are expected to address biological relevance (why the biomarker reflects disease mechanisms or clinically meaningful states), analytical performance (how reliably and accurately the biomarker can be measured), and early clinical evaluation (initial evidence that the biomarker relates to human disease features or outcomes). While animal or other preclinical studies can be part of the project, they are not sufficient on their own. A key requirement is preliminary human evaluation using carefully standardized human samples or human datasets. That typically means the proposal should include a clear plan for working with well-characterized specimens or rigorously curated data, with attention to consistency in collection, handling, and measurement so results are interpretable and reproducible.

The funding mechanism uses the R61/R33 phased award structure, which is meant to support milestone-driven progression from earlier, high-impact feasibility work to a more mature stage of development within the same overall project. The R61 phase generally supports early, critical proof-of-concept steps and de-risking activities, while the R33 phase supports continued development once the project meets predefined milestones. The announcement is also labeled "Clinical Trial Optional," meaning applicants may propose a clinical trial if it fits the biomarker development goals, but a clinical trial is not required to be responsive. The overall deliverable NIH is pushing for is a biomarker or composite biomarker that is sufficiently characterized and supported by early human evidence so that it is ready to enter definitive analytical validation and clinical validation studies after this award.

Eligibility is broad and includes many types of U.S.-based organizations and government entities. Eligible applicants include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; and Native American tribal organizations that are not federally recognized. Both nonprofit organizations (with or without 501(c)(3) status) and for-profit organizations (other than small businesses) are eligible, as are small businesses and other categories listed by NIH. The FOA also explicitly highlights additional eligible applicant types such as Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), along with faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions.

At the same time, the FOA places clear limits on foreign involvement. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible to apply under this opportunity. In other words, the applicant organization and the work supported under this FOA must be U.S.-based, consistent with the eligibility restrictions stated in the announcement.

From an administrative perspective, this is a discretionary grant opportunity offered by the National Institutes of Health under CFDA numbers 93.853 and 93.866. The opportunity was created on 2024-10-28, and the original closing date listed is 2028-01-07. An award ceiling is not specified in the provided source information, and the expected number of awards is not listed in the excerpt, which typically means applicants should consult the full FOA text for budget expectations, institute-specific guidance, and any limits or typical ranges NIH intends for awards under this program.

Overall, the opportunity is best understood as NIH support for the middle ground between discovery and full validation: enough funding and structure to identify and stress-test candidate biomarkers, prove they can be measured reliably, and show early signals of clinical relevance in humans, with the explicit endpoint of handing off a strong candidate biomarker or biomarker signature that is ready for rigorous validation and, eventually, use in neurotherapeutic development and clinical practice.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Development of Biomarkers or Composite Biomarkers for Neurological and Neuromuscular Disorders (R61/R33 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853, 93.866.
• This funding opportunity was created on 2024-10-28.
• Applicants must submit their applications by 2028-01-07.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 024

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