Integrating Biospecimen Science Approaches into Clinical Assay Development (U01 Clinical Trial Not Allowed) | PAR 25 325

Opportunity Information: Apply for PAR 25 325

Integrating Biospecimen Science Approaches into Clinical Assay Development (U01 Clinical Trial Not Allowed) is a National Cancer Institute (NCI) funding opportunity that focuses on a common but often under-addressed reason clinical biomarker assays struggle to perform consistently: preanalytical variability. In plain terms, even before a sample ever reaches an instrument or an assay workflow, the way a biospecimen is collected, handled, processed, transported, and stored can alter what is being measured. This NOFO is designed to fund investigator-led studies that systematically characterize those sources of variation and develop practical, evidence-based ways to reduce them so that downstream clinical assay development and analytical validation can move faster and with fewer failures.

The core scientific goal is to understand how specific preanalytical conditions change the measurable levels, integrity, or detectability of emerging and clinically relevant biomarkers across different testing platforms. The program is not restricted to one sample type. It explicitly supports work on tumor tissue biopsies, with an emphasis on small and clinically common specimens such as core biopsies and small excision samples, where limited material and rapid degradation can create major challenges. It also supports blood-based biospecimens used for liquid biopsy applications, where factors like tube type, time-to-processing, centrifugation conditions, temperature excursions, freeze-thaw cycles, and storage duration can meaningfully affect analytes such as circulating tumor DNA, RNA, proteins, extracellular vesicles, metabolites, and immune markers. Beyond tissue and blood, the NOFO invites studies involving tissue swabs, tissue secretions, pleural and esophageal aspirates, feces, and a wide range of bodily fluids including sweat, urine, cerebrospinal fluid, breast milk, and saliva, reflecting the growing clinical interest in less invasive sampling and multi-omic biomarker development.

The expected research approach is experimental and mechanistic rather than descriptive. Applicants are meant to design controlled comparisons that isolate key variables in procurement and handling, then quantify the impact on biomarker readouts using clinically relevant analytical methods. That can include evaluating how delays in fixation or stabilization influence nucleic acid fragmentation, how different anticoagulants alter downstream measurements, how specimen volume constraints affect extraction efficiency, or how storage temperatures and durations change protein stability or microbial signatures. Because the NOFO is centered on assay development and analytical validation readiness, the intended deliverables are the kinds of findings that can translate into standardized operating procedures, acceptance criteria, and best-practice recommendations that laboratories and clinical sites can realistically adopt.

The larger outcome NCI is aiming for is to speed up the path from biomarker discovery to reliable clinical testing by reducing avoidable noise introduced before analysis even begins. By generating evidence that links specific preanalytical factors to specific measurement failures or biases, the program seeks to support harmonized handling practices that make assay results more reproducible across sites, studies, and patient populations. This is particularly important for modern oncology biomarker work, where small biopsies, longitudinal sampling, and multi-site trials can magnify the consequences of inconsistent collection and processing.

Mechanistically, the award is a U01 cooperative agreement, meaning recipients should expect substantial scientific involvement from NIH/NCI staff compared with a standard investigator-initiated research grant. The NOFO is labeled "Clinical Trial Not Allowed," which generally means the funded activities should not include prospective assignment of human participants to interventions to evaluate health outcomes. The research can still involve human specimens and associated data, but the scope should stay focused on biospecimen science, preanalytical variables, and assay-related performance rather than interventional clinical testing.

Eligibility is broad and includes many types of domestic institutions and organizations, such as state and local governments, public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (including small businesses, though excluding small business-only mechanisms), independent school districts, and eligible tribal entities and housing authorities. The NOFO also highlights additional eligible applicant categories, including historically underserved or mission-specific institutions such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, and AANAPISI institutions, as well as faith-based or community-based organizations. Foreign (non-U.S.) organizations and regional organizations are also listed as eligible, and U.S. territories or possessions may apply, signaling an interest in solutions that can generalize across different healthcare settings and collection environments.

Key administrative details from the listing include the opportunity number PAR-25-325, the agency as the National Institutes of Health (with NCI as the sponsoring institute), the funding instrument as a cooperative agreement (U01), and an original closing date of September 10, 2027. The CFDA/assistance listing number associated with the opportunity is 93.393. The award ceiling and expected number of awards are not specified in the provided source data, which usually means applicants should consult the full NOFO text and any accompanying NCI budget guidance to understand typical project sizes, allowable costs, and programmatic priorities.

Overall, this opportunity is aimed at teams who can bridge biospecimen science and assay development: people who understand both the clinical realities of specimen collection and the analytical realities of biomarker measurement. Successful projects will likely be those that clearly identify high-impact, real-world preanalytical problems, test them rigorously, and produce actionable guidance that improves the reliability and validation readiness of clinical assays built on tumor tissue, liquid biopsies, or other emerging biospecimen types.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Integrating Biospecimen Science Approaches into Clinical Assay Development (U01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.393.
• This funding opportunity was created on 2024-12-13.
• Applicants must submit their applications by 2027-09-10.
• 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 25 325

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: