Discovery of Biomarkers and Biomarker Signatures for Neurological and Neuromuscular Disorders (R61/R33 Clinical Trial Optional) | PAR 19 315

Opportunity Information: Apply for PAR 19 315

The NIH grant opportunity titled "Discovery of Biomarkers and Biomarker Signatures for Neurological and Neuromuscular Disorders (R61/R33 Clinical Trial Optional)" (Funding Opportunity Number PAR 19 315; CFDA 93.853) is designed to push promising biomarkers from the early idea stage toward being truly usable tools in neurotherapeutic development and, ultimately, clinical care. The main aim is not late-stage validation, but the earlier, critical step of discovering biomarkers and/or biomarker signatures and then doing the first round of biological, analytical, and clinical evaluation so that the best candidates can graduate into full, definitive validation studies later on. In practical terms, NIH is looking for projects that can identify strong signals and show enough rigor and real-world feasibility that the resulting biomarkers are credible and ready for more expensive, large-scale validation efforts.

A key point in this announcement is its emphasis on neurological and neuromuscular disorders, with an explicit expectation that biomarker work will be connected to real use cases in clinical development. That includes biomarkers that could help select patients, stratify subtypes, monitor disease progression, confirm target engagement, predict response, or track treatment effects in ways that make clinical trials more efficient and informative. The FOA also recognizes that, in many disorders, a single marker may not be sufficient, so it encourages biomarker signatures, meaning combinations or patterns across multiple measurements (for example, multi-analyte panels, multimodal imaging plus fluid markers, or integrated molecular and digital measures) that together provide stronger clinical signal than any single readout.

Methodologically, the FOA allows animal studies as part of the overall evidence package, but it makes clear that animal-only projects are not enough. Every supported project must include preliminary human evaluation using carefully standardized human samples or datasets. This requirement is important because many biomarkers look promising in preclinical systems but fail when confronted with human biology, real clinical heterogeneity, differences in sample collection, or technical variability across sites. By requiring early human testing with well-controlled specimens or well-curated datasets, NIH is signaling that successful applications should plan for standardization, quality control, and careful interpretation from the beginning rather than treating those elements as afterthoughts.

The mechanism is an R61/R33, which is a phased award structure intended to support a milestone-driven pipeline. The R61 phase is typically used for the early, high-impact work needed to establish feasibility and generate convincing initial evidence. If the project meets predefined milestones, it can transition to the R33 phase, where the work expands into more substantial development and evaluation, still short of the final, definitive validation but far enough along to yield candidates that are genuinely ready for that next step. This structure is meant to reduce the risk of investing heavily in biomarker ideas that cannot be standardized, cannot be measured reliably, or do not show a clear signal in humans. The listing also notes "Clinical Trial Optional," meaning applicants can propose clinical trials if they are appropriate to the biomarker development plan, but a clinical trial is not required for all projects.

In terms of eligibility, this is a broad, discretionary NIH grant opportunity open to a wide range of organizations. 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; other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding higher education institutions in those categories); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly highlights additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, certain non-federally recognized tribal governments, regional organizations, U.S. territories or possessions, eligible federal agencies, and even non-U.S. entities (foreign organizations). This breadth reflects NIH interest in drawing strong biomarker ideas from many settings, including community-based and international contexts, as long as the proposed work meets the scientific and rigor expectations.

Administrative details from the source information indicate this is a grant (Funding Instrument Type: Grant) in the health category, administered by the National Institutes of Health, with an original closing date listed as 2022-05-07 and a creation date of 2019-07-10. While those dates describe the specific posting, the core summary remains the same: NIH is funding milestone-driven projects that discover and conduct early evaluation of biomarkers and biomarker signatures for neurological and neuromuscular diseases, with mandatory preliminary evaluation in humans using standardized samples or datasets, aiming to produce candidates mature enough to enter definitive analytical and clinical validation studies.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Discovery of Biomarkers and Biomarker Signatures 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.
• This funding opportunity was created on 2019-07-10.
• Applicants must submit their applications by 2022-05-07. (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.

Apply for PAR 19 315

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