Exploratory Clinical Trials and Studies of Natural Products in NCCIH High Priority Research Topics (R33) | PAR 16 419

Frequently Asked Questions (FAQs)

What is the PAR-16-419 R33 funding opportunity?

PAR-16-419 is a National Institutes of Health (NIH) grant opportunity that supports exploratory clinical trials and clinical studies of natural products aligned with NCCIH high-priority research topics. It uses the R33 mechanism to generate practical, decision-driving human data that helps determine whether and how a larger, definitive clinical trial should be pursued.

What is the main purpose of this R33 program?

The purpose is to move promising natural products toward stronger, evidence-based clinical development by funding carefully designed early-stage human studies. These studies are intended to close key knowledge gaps and provide actionable information for planning (or not planning) a future full-scale clinical trial.

What kinds of products are considered "natural products" under this opportunity?

The opportunity specifically points to natural products such as botanicals, dietary supplements, and probiotics. The emphasis is on products that already have a strong scientific rationale suggesting they are worth more rigorous study in humans.

Is this FOA intended to fund a full randomized controlled trial (RCT) to prove efficacy?

No. This FOA is not meant to fund a full RCT designed to prove clinical efficacy on health outcomes. Instead, it supports exploratory trials and studies that produce high-utility data to inform whether a later definitive efficacy trial is justified and how it should be designed.

What does "exploratory clinical trial" mean in the context of this R33?

In this context, an exploratory clinical trial is an early-stage human study designed to answer practical questions that influence next development steps. The goal is to generate clear, interpretable results that support concrete decisions about further development and future trial readiness rather than delivering final proof of clinical benefit.

What types of questions should an R33 study be designed to answer?

Studies should be designed to answer decision-driving questions about the natural product and its use in humans, such as how dosing or regimen should be optimized, whether the product shows tolerability or safety signals in the intended population, and whether credible measures indicate biologic activity or target engagement.

What kinds of study aims appear consistent with the intent of this FOA?

While the excerpt does not list every allowable study type, the stated intent is consistent with studies that support feasibility and readiness for a later definitive trial. Examples mentioned or implied include evaluating recruitment and retention capability, optimizing dose and regimen, assessing tolerability and safety signals, confirming target engagement or biologic activity using credible measures, characterizing variability in response, testing procedures for product standardization and quality control in a clinical setting, and refining outcome measures for later use in a larger trial.

Why does the FOA emphasize interpretable results even if findings are negative?

The FOA emphasizes that even if the product does not perform as hoped, the study should still yield valuable information that determines next steps. That could include refining the formulation, adjusting dosing, reconsidering the target population, improving adherence strategies, selecting better biomarkers, or deciding that further development is not justified.

How should applicants think about "success" for an R33 project under this FOA?

Success is framed as producing actionable evidence that guides a go/no-go (or redesign) decision for subsequent clinical development. A strong project is one where the outcomes, whether positive or negative, directly inform whether a full-scale trial should proceed and what its design should look like.

What agency sponsors this opportunity?

The sponsoring agency is the National Institutes of Health (NIH), and the program is associated with NCCIH priorities as described in the opportunity summary.

What is the CFDA number and activity category?

The activity category is Health under CFDA 93.213.

What type of funding instrument is this?

This is a discretionary grant.

When was the opportunity record created and what closing date is shown?

The opportunity record was created on September 1, 2016, and the original closing date shown is December 16, 2016.

Does the excerpt provide the award ceiling or expected number of awards?

No. The excerpted record does not provide an award ceiling or the expected number of awards. Applicants are expected to confirm budget limits, project period, and current submission dates in the full FOA text and any related NIH Guide notices.

Who is eligible to apply?

Eligibility is broad and includes many U.S.-based organizations, including state, county, and city/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; Native American tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other eligible entities.

Are minority-serving institutions and community-based organizations included as eligible applicants?

Yes. The FOA highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, and faith-based or community-based organizations.

Are U.S. territories or possessions eligible?

Yes. The FOA explicitly mentions U.S. territories or possessions among eligible applicants.

Can federal agencies apply?

Yes. The FOA includes eligible federal agencies among the additional eligible applicants.

Can a non-U.S. (foreign) institution apply as the main applicant?

No. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply as the applicant organization under this FOA.

Are non-domestic components of U.S. organizations eligible to apply?

No. Non-domestic components of U.S. organizations are also not eligible to apply.

Are any international collaborations allowed at all?

Yes, foreign components are allowed as defined by the NIH Grants Policy Statement. In practice, a U.S.-based applicant may include certain justified international elements or collaborations that meet NIH definitions, but a foreign organization cannot serve as the primary applicant under this FOA.

How does this R33 opportunity fit into the overall clinical development pathway?

It is positioned as a bridge between promising preclinical or early human evidence and the level of preparation needed for a definitive efficacy trial. The emphasis is on generating evidence that improves the design and competitiveness of a subsequent full-scale clinical trial application.

What makes an application likely to be competitive based on the excerpt?

Based on the provided information, competitive applications are likely to pair a well-justified natural product (including credible rationale and attention to product characterization and quality considerations) with a clinical study plan that aligns with NCCIH high-priority topics and produces actionable evidence about readiness for larger-scale testing and how that next trial should be designed.

Does the excerpt specify the exact list of NCCIH high-priority research topics?

No. The excerpt references NCCIH high-priority research topics but does not provide the list. Applicants would need to consult the full FOA text for the specific topics and requirements.

Does the excerpt state specific budget limits, project periods, or current submission dates?

No. The excerpt indicates that applicants should confirm budget limits, project period, and current submission dates in the full FOA and related NIH notices.