Pilot Projects Increasing the Impact of the NIH Centers for Advancing Research on Botanicals and Other Natural Products (PI2 CARBON) (R03 Clinical Trials Not Allowed) | PAR 20 228

Opportunity Information: Apply for PAR 20 228

The NIH funding opportunity PAR-20-228, titled "Pilot Projects Increasing the Impact of the NIH Centers for Advancing Research on Botanicals and Other Natural Products (PI2 CARBON) (R03 Clinical Trials Not Allowed)," is a small, targeted grant meant to spark new pilot studies on botanicals and other chemically complex natural products that may affect human health. The program is designed around the idea that many natural products are mixtures of numerous compounds, and understanding what they do biologically (and why) often requires specialized materials, chemistry, analytical platforms, and biological testing pipelines. Rather than building all of that from scratch in every lab, NIH is using this mechanism to connect outside investigators to established NIH-funded Centers that already have curated products, standardized methods, and ongoing lines of investigation.

A defining requirement of this FOA is true collaboration with one or more NIH Centers for Advancing Research on Botanicals and Other Natural Products (CARBON). In practical terms, applicants must include letters of support at the time of submission that document collaboration with one or more of the U19 Botanical Dietary Supplements Research Centers that were awarded in 2020. The collaboration is not optional or incidental; it is a "critical element" of the project, meaning the science and feasibility of the proposal should clearly depend on access to the Center's expertise, resources, products, datasets, specimens, or methods. The goal is to increase the scientific return on the CARBON program by enabling additional investigators to use what the Centers have built, while also generating preliminary data that can grow into larger projects later.

The kinds of studies encouraged under this announcement focus on two broad scientific themes. First, projects can examine potential effects of chemically complex natural products that are relevant to human health, which can include beneficial effects, adverse effects, or interactions that matter for safety and efficacy. Second, projects can dig into causal and molecular mechanisms of action underlying observed effects, with an emphasis on moving beyond descriptive findings and toward mechanistic understanding. The FOA is flexible in terms of specific natural products and health areas, but it expects applicants to connect tightly to the CARBON Centers' existing products or capabilities.

NIH is explicit about how these pilot projects should leverage the CARBON infrastructure. With agreement from the collaborating Center(s), a project may use products already being studied by those Centers to extend understanding of their biological effects or mechanisms. Alternatively, a project can study other complex natural products as long as it uses methods developed and used within the Centers, such as specialized chemical characterization approaches, bioassay workflows, standardization strategies, or other Center-developed platforms that improve rigor and reproducibility for natural product research. This emphasis reflects a common challenge in the field: results can vary dramatically depending on how a product is sourced, prepared, chemically profiled, and tested, so NIH is steering applicants toward standardized resources and proven methodologies.

In terms of research approach, the FOA allows a spectrum from basic lab and bench work through in vitro studies and non-human animal models. Even though the mechanism is labeled "Clinical Trials Not Allowed," the announcement still notes that, where feasible and appropriate, projects may obtain additional feasibility or outcome information from clinical trials already being performed by CARBON awardees. The key limitation is that the R03 project itself should not propose and run a new clinical trial. Instead, an applicant might add additional measures within an ongoing CARBON trial (when the Center agrees and it fits within the existing trial framework) or perform secondary analyses of existing clinical data, biospecimens, or other trial-derived materials. This creates a path for human-relevant insights without launching a new interventional clinical study under this award.

The award uses the NIH R03 mechanism, which is commonly used for short-term, limited-scope projects that generate preliminary data, test a new idea, or establish feasibility. The listed award ceiling is $50,000, signaling that NIH expects a tightly focused pilot with clear aims and a realistic plan that can be completed with modest funds. Because the purpose is to increase impact and accelerate discovery, the strongest applications are likely to be those that propose a well-defined question, make efficient use of Center resources, and produce concrete outputs such as mechanistic evidence, validated assays, preliminary efficacy/safety signals (from non-trial work or permitted secondary analyses), or datasets that can support a larger follow-on application.

Eligibility is broad and includes many types of organizations. Standard eligible applicants include state, county, city or township 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; public housing authorities/Indian housing authorities; and a wide range of nonprofit organizations, both with and without 501(c)(3) status. For-profit organizations (other than small businesses) and small businesses are also eligible, along with other categories NIH may allow. The FOA also highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions; Asian American, Native American, and Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); tribal governments that are not federally recognized; U.S. territories or possessions; faith-based or community-based organizations; eligible federal agencies; regional organizations; and even non-U.S. entities (foreign organizations). This wide eligibility is consistent with the collaborative nature of the program, since specialized expertise in natural products, analytical chemistry, pharmacology, toxicology, and related fields can be distributed across many sectors.

Administratively, the opportunity is run by the National Institutes of Health and is categorized under health-related funding activity (CFDA numbers 93.213 and 93.321). The original closing date listed is 2023-03-01, and the FOA was created on 2020-06-08, indicating it is part of a multi-year NIH initiative to amplify the productivity and reach of the CARBON Centers funded in 2020. Overall, the grant is best understood as a structured way to plug new pilot ideas into an established NIH natural products research ecosystem, with collaboration and leveraging of Center resources as the central requirements and with mechanistic, human-health-relevant questions as the core scientific priority.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Pilot Projects Increasing the Impact of the NIH Centers for Advancing Research on Botanicals and Other Natural Products (PI2 CARBON) (R03 Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213, 93.321.
• This funding opportunity was created on 2020-06-08.
• Applicants must submit their applications by 2023-03-01. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $50,000.00 in funding.
• 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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