Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional) | PAR 25 055

Opportunity Information: Apply for PAR 25 055

The NIH funding opportunity PAR-25-055, titled "Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional)," is a cooperative agreement designed to move promising neurological and neuromuscular biomarkers from the "we think this works" stage to the "this is clinically reliable" stage. The core aim is not discovery of new biomarkers or early assay development, but rigorous clinical validation of an already well-supported candidate biomarker in the intended patient population. In practical terms, the program is trying to generate the kind of evidence that would stand up to regulatory expectations, including FDA-aligned performance metrics, by establishing how well the biomarker predicts what it is supposed to predict in real clinical settings.

A central emphasis of the announcement is measuring clinical predictive performance, specifically positive predictive value (PPV) and negative predictive value (NPV), within the clinical population where the biomarker is meant to be used. That focus signals that applications should be designed around real-world decision contexts, where prevalence, patient selection, and disease heterogeneity strongly influence PPV and NPV. The opportunity is essentially asking applicants to design studies that can credibly answer questions like: when the biomarker result is positive, how likely is it that the patient truly has (or will develop, worsen, respond, etc.) the condition of interest; and when the result is negative, how confident can clinicians be that the condition is absent (or that progression/response will not occur) within the defined context of use. The intent is to produce evidence that supports clinical confidence and potential downstream qualification or adoption pathways.

The program also makes clear assumptions about readiness. To be responsive, a project should already have (1) a clearly identified candidate biomarker with strong preliminary support, (2) a detection method or assay technology that has been developed and analytically validated, and (3) a defined clinical or research need along with an articulated potential "context of use" for the biomarker. In other words, the biomarker and its measurement approach should be past the exploratory phase. The work proposed under this PAR should concentrate on validating the biomarker measurement in the relevant patient population, rather than building the assay from scratch, optimizing basic detection chemistry, or performing open-ended discovery studies.

The funding mechanism is a U01 cooperative agreement, which typically means there is substantial NIH involvement during the project compared with a standard investigator-initiated grant. Applicants should expect collaborative stewardship, milestone-driven oversight, and an expectation that study design, performance benchmarks, and data quality practices will be strong enough to support broad confidence in the findings. The notice also states "Clinical Trial Optional," meaning the proposed work may include a clinical trial if it is necessary for validation, but a trial is not mandatory; well-designed observational or prospective cohort validation studies may be appropriate depending on the biomarker and intended use.

Eligibility is broad across public and private sectors, reflecting NIH's goal of attracting capable teams wherever they are based. Eligible applicants include state, county, and local 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 Native American tribal organizations that are not federally recognized. Nonprofits are eligible whether or not they have 501(c)(3) status, and both for-profit organizations (other than small businesses) and small businesses may apply. The announcement explicitly highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIS institutions, Hispanic-serving institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions.

At the same time, the geographic rules are specific: non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components as defined by the NIH Grants Policy Statement are allowed, which generally means a U.S.-based applicant can include certain international elements (for example, specific collaborations or performance sites) if they meet NIH policy requirements and are justified scientifically, but the applicant organization itself must be U.S.-based.

From the administrative details provided, the sponsoring agency is the National Institutes of Health, the opportunity category is discretionary, and the activity category is health under CFDA 93.853. The opportunity was created on 2024-10-02, and the original closing date listed is 2026-06-22. The award ceiling and expected number of awards are not specified in the provided extract, which usually means applicants need to consult the full announcement and any linked institute-specific guidance to understand budget expectations, project period norms, and how many awards might be anticipated.

Overall, PAR-25-055 is best understood as a translational validation bridge: it is aimed at teams who already have a strong biomarker candidate and a working, analytically validated measurement method, and who now need to prove, in the real clinical population and with FDA-consistent rigor, that the biomarker meaningfully predicts clinically relevant states or outcomes within a clearly defined context of use. The deliverable NIH is pushing for is high-quality evidence of performance (including PPV and NPV) that can support confident clinical interpretation and future regulatory or clinical implementation steps.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Clinical 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 25 055

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