Clinical Validation of a Candidate Biomarker for Neurological Disease (U44 - Clinical Trial Optional) | PAR 18 548

Opportunity Information: Apply for PAR 18 548

Clinical Validation of a Candidate Biomarker for Neurological Disease (U44 - Clinical Trial Optional), funding opportunity number PAR 18 548, is a National Institutes of Health (NIH) discretionary funding announcement that uses a cooperative agreement mechanism (U44). It is aimed specifically at Small Business Concerns (SBCs) and is designed to move a neurological disease biomarker from the "promising candidate" stage into a clinically validated tool that can be trusted in real-world research and care settings. The central emphasis is on rigorous clinical validation, meaning the work should demonstrate that the biomarker performs reliably in people and in the types of settings where it is intended to be used, rather than simply showing early feasibility or exploratory correlations.

The FOA is built around a clear set of prerequisites, so it is not meant for discovery research or early assay development. It assumes that a candidate biomarker has already been identified, that an analytical method (the actual test or measurement approach) has already been developed and validated in a way that matches the biomarker's intended purpose, and that there is already a working hypothesis for the biomarker's context of use. In practice, "context of use" refers to how the biomarker is supposed to function in the clinical or trial ecosystem, such as aiding diagnosis, predicting prognosis, tracking disease progression, measuring pharmacodynamic response, enriching clinical trial enrollment, or serving as a surrogate or supportive endpoint. Applications are expected to align the validation plan directly with that intended use, rather than validating the biomarker in a vague or overly broad way.

From a study design perspective, the announcement supports clinical validation using retrospective methods, prospective methods, or a combination of both. Retrospective validation typically leverages existing patient samples, datasets, or completed studies to test whether the biomarker behaves as expected, while prospective validation collects new data under predefined protocols to reduce bias and better mirror how the biomarker would perform when used going forward. The overarching objective is to generate strong evidence that the biomarker is robust and reliable enough for multi-site clinical trials and, ultimately, clinical practice. This multi-site emphasis matters because a biomarker that only works in a single lab or a single clinic often fails when exposed to the variability of different sites, operators, instruments, and patient populations.

Because the funding instrument is a cooperative agreement, recipients should expect a more hands-on partnership with NIH than they would under a standard grant. Cooperative agreements generally involve substantial programmatic involvement from the funding agency, which can include coordinated milestones, steering or monitoring input, and ongoing interaction to ensure that the validation effort stays aligned with program goals and maintains the level of rigor needed for broad adoption.

Eligibility is limited to small businesses, and the FOA explicitly states that non-U.S. (foreign) institutions are not eligible to apply, and non-U.S. components of U.S. organizations are also not eligible to apply. However, foreign components, as defined under the NIH Grants Policy Statement, may be allowed in some circumstances, which typically means certain discrete elements of the work could potentially be performed abroad if strongly justified and consistent with NIH policy, even though the applicant organization itself must be U.S.-based and eligible.

Administratively, the opportunity is associated with CFDA number 93.853 and is categorized under health-related funding. The announcement was created on December 22, 2017, and the original closing date listed is September 7, 2020. The provided source information does not specify an award ceiling or the number of expected awards, so applicants would normally need to consult the full FOA or related NIH documentation for budget limits, project periods, and any institute-specific considerations tied to the participating NIH institute or center. Overall, the opportunity is best suited to small businesses that already have a well-defined biomarker and validated analytical method in hand, and are ready to execute a well-powered, carefully controlled clinical validation plan that can stand up to scrutiny across multiple sites and ultimately support adoption in trials and clinical decision-making.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Clinical Validation of a Candidate Biomarker for Neurological Disease (U44 - 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 2017-12-22.
• 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: Small businesses.

Apply for PAR 18 548

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