Exploratory Clinical Trials and Studies of Natural Products in NCCIH High Priority Research Topics (R61/R33) | PAR 16 418

Opportunity Information: Apply for PAR 16 418

The Exploratory Clinical Trials and Studies of Natural Products in NCCIH High Priority Research Topics (R61/R33) funding opportunity (PAR-16-418) is a National Institutes of Health (NIH) discretionary grant program administered in the health research area (CFDA 93.213). Its central purpose is to fund early-stage, pilot clinical studies of natural products, specifically botanicals, dietary supplements, and probiotics, when there is a strong scientific premise suggesting the product is worth more rigorous clinical development. The program is structured to generate practical, decision-grade evidence that helps the field determine whether a natural product should advance to a larger and more definitive clinical trial, or whether development should stop or be redirected based on what is learned.

A key feature of this opportunity is what it is designed to fund and what it is not designed to fund. The FOA is explicitly aimed at exploratory, information-rich clinical trials and studies that address critical knowledge gaps, rather than a full randomized controlled trial (RCT) intended to prove efficacy on clinical outcomes. In other words, applicants are expected to design studies that produce results with high scientific utility even if the findings are negative. The emphasis is on collecting the kinds of data that make subsequent research more rigorous and competitive, such as feasibility information, dosing and regimen considerations, adherence, recruitment and retention metrics, safety and tolerability signals, product characterization issues relevant to human studies, and other mechanistic or translational endpoints that clarify whether and how a natural product might merit a larger confirmatory trial. The overall expectation is that the pilot data will directly inform go/no-go decisions about further testing or product development, rather than serve as a stand-alone efficacy demonstration.

The award mechanism uses the R61/R33 phased innovation approach, which generally supports a two-stage pathway. The first phase (R61) supports exploratory or pilot work that establishes whether the project can meet predefined milestones, and the second phase (R33) supports an expanded set of activities if those milestones are achieved. In practical terms, applicants should be prepared to propose clear, measurable milestones that determine progression from the pilot stage to the next stage, aligned with the FOA's goal of producing actionable evidence for future clinical testing. The design philosophy is that the study should be robust enough to answer important development questions while still being appropriately sized and scoped for an exploratory clinical effort.

Eligibility is broad and spans many types of domestic organizations. Eligible applicants include state, county, city or township, and 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; Native American tribal organizations other than federally recognized tribal governments; public housing authorities and Indian housing authorities; nonprofits with 501(c)(3) status and nonprofits without 501(c)(3) status (in both cases, other than institutions of higher education); for-profit organizations other than small businesses; small businesses; and other eligible entities. The FOA also calls out additional eligible applicant categories, including 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, regional organizations, Indian/Native American tribal governments other than federally recognized, and U.S. territories or possessions.

Foreign eligibility is limited. Non-domestic (non-U.S.) entities and non-domestic (non-U.S.) components of U.S. organizations are not eligible to apply as applicants. However, foreign components are allowed as defined by the NIH Grants Policy Statement, meaning a U.S. applicant may include certain foreign elements of the project when they are justified and meet NIH policy requirements. This distinction matters for teams that want to incorporate specialized assays, product sourcing, or collaborations outside the United States; those activities may be possible only as foreign components within an eligible U.S.-led application, not as a foreign applicant-led submission.

From an administrative standpoint, the opportunity was created on September 1, 2016, and the original closing date listed is December 16, 2016. The source information does not specify an award ceiling or expected number of awards in the provided fields, so applicants would typically look to the full FOA text and NIH institute guidance for budget expectations, scope norms, and any programmatic priorities tied to NCCIH high-priority research topics. The bottom line is that this program supports carefully designed, milestone-driven exploratory clinical research on natural products that yields high-value evidence to guide the next steps toward a future, competitive full-scale clinical trial, without positioning the funded project itself as the definitive efficacy RCT.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Exploratory Clinical Trials and Studies of Natural Products in NCCIH High Priority Research Topics (R61/R33)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213.
• This funding opportunity was created on 2016-09-01.
• Applicants must submit their applications by 2016-12-16. (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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