Analytical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders(U01 Clinical Trial Optional) | PAR 25 050

Opportunity Information: Apply for PAR 25 050

This NIH funding opportunity (PAR 25-050) supports projects that take a promising biomarker for a neurological or neuromuscular disorder and do the hard, method-focused work needed to prove the biomarker can be measured reliably enough for real-world use. The emphasis is on analytical validation of the measurement method(s), meaning applicants are expected to rigorously test and document how well the assay or detection approach performs, so the resulting biomarker readout can be trusted in clinical trials and, potentially, in clinical practice. The award mechanism is a U01 cooperative agreement, which typically means NIH staff will have substantial scientific involvement during the project, and the NOFO is labeled "Clinical Trial Optional," so a clinical trial is not required but may be proposed if it fits the validation goals.

A central expectation is that applicants clearly explain why the biomarker is needed and what problem it solves. That includes describing the unmet need in the disease area, why existing biomarkers or tools are inadequate, and why the proposed measurement method is the right approach. Applicants must also define one or two specific "contexts of use" for the biomarker. In practical terms, this means stating exactly how the biomarker will be used (for example, patient selection, prognosis, pharmacodynamic response, disease monitoring, or another clearly articulated use case) and in what setting (clinical trial decision-making, routine clinical care, or another specified scenario). The NOFO is not asking for general biomarker discovery; it is asking for a focused plan that ties a specific biomarker measurement method to a defined use case and then demonstrates that the method performs to a standard appropriate for that use.

The work supported under this announcement includes optimizing the assay and then evaluating key analytical performance characteristics. That includes accuracy and precision (how close measurements are to the true value and how consistent they are), the reportable range (the range over which the assay can produce reliable quantitative results), and analytical sensitivity and specificity (how well the method detects the biomarker when it is present and avoids false detection when it is not, in the analytical sense). The NOFO also calls for evaluation across multiple sites and operators, highlighting a goal of showing that results are reproducible beyond a single lab or a single highly specialized technician. Multi-site applications are expected but not strictly required, so an applicant can propose a single-site plan if it is well justified, but the overall intent is to produce evidence that the method can perform robustly under conditions similar to those seen in multicenter trials or broader clinical deployment.

Beyond performance testing, applicants are expected to establish practical infrastructure for dependable measurement. This includes developing reference intervals (benchmarks for interpreting results, such as what is considered typical across relevant populations) and putting quality control procedures in place. In effect, the NOFO is aimed at moving a biomarker method from "promising but variable" to "standardized and defensible," where sample handling, instrument calibration, operator training, and ongoing QC are defined clearly enough that other groups can reproduce the results and regulators, trial sponsors, and clinicians can have confidence in the readouts.

The opportunity is offered by the National Institutes of Health under CFDA 93.853 in the health funding category. The application due date listed is June 22, 2026. Eligibility is broad and includes many types of U.S.-based organizations and governments: state, county, and city governments; 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 other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other eligible entities. The NOFO also explicitly highlights a range of institution types as other eligible applicants, including HBCUs, Hispanic-serving institutions, Tribal Colleges and Universities, AANAPISI institutions, Alaska Native and Native Hawaiian serving institutions, faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions.

Foreign organizations are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible to apply. However, foreign components are allowed as defined by the NIH Grants Policy Statement, meaning a U.S. applicant organization may include certain foreign elements in the project when they are justified and structured according to NIH policy, even though a non-U.S. organization cannot be the applicant.

Overall, the NOFO is best read as a bridge-building program for biomarkers in neurology and neuromuscular disease: it funds the analytical groundwork needed to standardize and prove an assay so that a biomarker can be used confidently for a specific purpose in trials or practice, with a strong preference for demonstrating reproducibility across people and places, and for producing the reference ranges and quality systems that make the method deployable rather than merely publishable.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Analytical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders(U01 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.
• This funding opportunity was created on 2024-10-02.
• Applicants must submit their applications by 2026-06-22. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 25 050

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