Clinical Validation of Candidate Biomarkers for Neurological Diseases (U01 Clinical Trial Optional) | PAR 18 664

Opportunity Information: Apply for PAR 18 664

The National Institutes of Health (NIH) funding opportunity titled "Clinical Validation of Candidate Biomarkers for Neurological Diseases (U01 Clinical Trial Optional)" (Funding Opportunity Number PAR-18-664) is designed to push promising neurological disease biomarkers past the discovery phase and into a level of evidence that makes them truly usable in real-world research and care. The program uses a U01 cooperative agreement mechanism, which generally means NIH staff will have an active role in shaping and overseeing the project as it progresses, rather than simply providing funds and stepping back. The overall aim is to strengthen the biomarker pipeline for neurological disorders by supporting well-controlled, clinically grounded validation studies that can support later use in multi-site clinical trials and, ultimately, clinical practice.

A key point of this FOA is that it is not meant for early biomarker discovery or initial assay development. It assumes three things are already in place before a team applies. First, a candidate biomarker has already been identified, so there is a specific biomarker target the applicants want to validate rather than a broad search effort. Second, an analytical method (the assay or measurement approach) has already been developed and validated in a way that matches the biomarker's intended purpose, meaning the proposal should not revolve around building the test from scratch but rather using a technically credible and fit-for-purpose measurement system. Third, applicants should already have a working hypothesis about the biomarker's context of use, which is essentially a clear statement of what the biomarker is supposed to do and in what setting, such as aiding diagnosis, predicting prognosis, monitoring disease progression, enriching clinical trial enrollment, or demonstrating pharmacodynamic response. The FOA is focused on the clinical validation step, using retrospective and/or prospective study designs, as long as the approach is aligned with the biomarker's intended use.

The work supported under this announcement is centered on rigorous clinical validation, meaning the studies should be designed to test whether the biomarker performs reliably and meaningfully in patient populations and clinical contexts, not just under ideal lab conditions. The emphasis on retrospective and prospective methods gives applicants flexibility: retrospective work could leverage existing cohorts, biobanks, or archived samples with strong clinical annotation, while prospective work could involve collecting new data or samples going forward under a standardized protocol. The phrase "Clinical Trial Optional" signals that applications may include a clinical trial component if it is appropriate for validation, but a clinical trial is not required in every case. The intended end result is a biomarker with enough evidence of robustness, reproducibility, and clinical relevance that it can be credibly used across multiple sites, which is a common stumbling block for biomarkers that look promising at single centers but fail to generalize.

In terms of eligibility, the FOA is broadly open across many sectors, reflecting NIH's intent to enable validation efforts that often require collaboration among academia, health systems, nonprofits, and industry. Eligible applicants include state, county, city or township governments, special district governments, and independent school districts, as well as public and state-controlled institutions of higher education and private institutions of higher education. It also includes federally recognized Native American tribal governments, tribal organizations that are not federally recognized governments, and public housing authorities/Indian housing authorities. Both nonprofits (with and without 501(c)(3) status, excluding institutions of higher education in those categories) and for-profit organizations (other than small businesses), along with small businesses, are eligible. The FOA also explicitly highlights additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, non-U.S. entities (foreign organizations), regional organizations, and U.S. territories or possessions. This breadth signals that NIH is open to biomarker validation efforts that may be international in scope, community-based, or rooted in diverse institutional settings, which can be important for ensuring biomarkers work across different populations and healthcare environments.

From an administrative standpoint, this is a discretionary grant opportunity in the health funding category, listed under CFDA number 93.853, with NIH as the sponsoring agency. The FOA record shows a creation date of February 14, 2018, and an original closing date of September 7, 2020. While the listing does not specify an award ceiling or the expected number of awards in the provided text, the cooperative agreement structure and the emphasis on multi-site readiness strongly suggest projects are expected to be well-organized, statistically sound, and operationally prepared for the realities of clinical validation, including standardized procedures, quality control, and clear plans for demonstrating performance consistent with the proposed context of use.

In practical terms, the opportunity is aimed at teams that already have a biomarker and a validated measurement method and now need support to prove, in a clinically meaningful way, that the biomarker is dependable and useful for a defined role in neurological disease research or care. The strongest fit for this FOA is a focused validation program that can convincingly demonstrate the biomarker's performance in the appropriate patient groups and settings, ideally in ways that would allow the biomarker to be deployed consistently across multiple sites and eventually adopted in clinical trials and clinical workflows.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Clinical Validation of Candidate Biomarkers for Neurological Diseases (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 2018-02-14.
• Applicants must submit their applications by 2020-09-07. (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.

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