Notice Number: NOT-OD-19-013
Key Dates
Release Date: October 09, 2018Estimated Publication Date of Funding Opportunity Announcement: November 14, 2018
First Estimated Application Due Date: April 15, 2019
Earliest Estimated Award Date: July 01, 2020
Earliest Estimated Start Date: July 01, 2020
Related Announcements
NOT-AT-19-002, Notice of Intent to Publish a Funding Opportunity Announcement for Center for Natural Product Technology, Methodology and Productivity Optimization (NP-TEMPO) (U41, Clinical Trial Not Allowed)
NOT-AT-19-003, Notice of Intent to Publish a Funding Opportunity Announcement for a Natural Products NMR Open Data Exchange (NODE) (U24, Clinical Trial Not Allowed)
Issued by
Office of Dietary Supplements (ODS)
Purpose
The Office of Dietary Supplements (ODS) and the National Center for Complementary and Integrative Health (NCCIH) with other NIH Institutes and Centers (ICs) to be determined, intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications for research to further advance the Centers for Advancing Research on Botanicals and Other Natural Products (CARBON) Program by publishing a set of linked FOAs for cooperative agreement applications.
The goal of this U19 , Botanical Dietary Supplements Research Centers (BDSRC) component of the CARBON.2 Consortium will be to support collaborative, trans-disciplinary research focused on obtaining information that will contribute significantly to the optimal design of future clinical trials of the effects on human resilience of orally consumed, complex botanical products. Products appropriate for applications responsive to the planned FOA will be limited to those for which there is rigorous, but not definitive, evidence supporting a clinically or public health significant, biologically and mechanistically plausible, and reproducible effect on, or relevant to, human biological or cognitive/behavioral resilience. Applications in which a purified phytochemical is the main focus will be considered unresponsive to the FOA. The BDSRC are expected to focus on developing the most critical data to inform the optimal design of future clinical trials of orally consumed complex botanical dietary supplements. Information acquired through achievement of the BDSRC specific aims is expected to signifiantly contribute to the design of optimally informative clinical trials, providing evidence for design decisions including, but not limited to, decisions about the appropriateness of the trial design (or of doing any trial with the product), as well as those regarding product formulations, doses, timing, eligibility criteria, participant characteristics to be collected, markers of proximal biological effect, outcome measures, etc.
Applicants applying under this BDSRC FOA are encouraged to collaborate, as appropriate, with the NMR Open Data Exchange (NODE), the Center for Natural Product Technology, Methodology and Productivity Optimization (NP-TEMPO), and other NCCIH, ODS, and NIH supported grantees .
This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.
The FOA is expected to be published in October, 2018, with an expected application due date in April, 2019.
This FOA will utilize the U19 activity code. .NIH U19 cooperative agreements support multi-project research programs directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary approach.?
Details of the planned FOA are provided below.
As detailed in the ODS Strategic Plan, ODS goals include expanding the knowledge base relevant to dietary supplements by stimulating and supporting a full range of biomedical research, and enhancing the dietary supplement research workforce through training and career development.
The NCCIH Strategic Plan incorporates advancing the understanding of basic biological mechanisms of action of natural products, and developing improved research methods for conducting rigorous studies of their integration into health care.
Research Initiative Details
The ODS, with NCCIH and interested IC partners, anticipates making U19 awards pursuant to the planned FOA to support trans-disciplinary Botanical Dietary Supplements Research Centers with specific aims that are expected to make substantial contributions to the optimal design of clinical trials of complex botanical products. Responsive applications will be supported by rigorous evidence for a clinically significant and meaningful, causal, biologically and mechanistically plausible, and reproducible effect on, or relevant to, human biological or cognitive/behavioral resilience.
Each BDSRC will be required to include a Botanical Research Core, as well as two research projects that synergize with each other, and are expected, separately and together, to provide information that will add substantial value to the existing body of data relevant to the optimal design of a future clinical trial of the effects on human resilience of orally consumed, complex botanical products for which there is rigorous, but not definitive, evidence for a clinically or public health significant, biologically and mechanistically plausible, and reproducible effect on, or relevant to, human biological or cognitive/behavioralresilience.
For the purposes of the BDSRC FOA, resilience will be defined as capacity to withstand and successfully adapt to change, disturbance, stress, etc., or to recover efficiently from disturbance, challenge, illness, etc. Applicants will be expected to use resilience models in which resilience can be measured quantitatively and objectively over relatively short time frames appropriate for a 5-year award. Examples of such outcomes include, but are not limited to restoration, in initially healthy individuals, of baseline microbiome ecology after disturbance, HbA1c levels, response to vaccine or viral challenge, time to return to initial or normal/healthy levels of inflammatory cytokines or blood glucose after a perturbation, or measures of fatigability.
This FOA complements the current suite of NCCIH natural product FOAs in its focus on complex, orally consumed natural products relevant to resilience, as well as in its greater focus on trans-disciplinary collaboration, which may enable questions such as optimal product composition and differences between responders and non-responders to be addressed simultaneously and synergistically in ways that help to elucidate causal molecular mechanisms of action.
The research supported under this FOA is intended to make a significant contribution to the optimal design of future clinical trials of the product studied. It should have the potential to indicate that further studies are unlikely to detect significant health benefit. In addition, the BDSRC are expected to provide a context for training of the next generation of trans-disciplinary researchers focused on the effects of complex, orally consumed botanicals on human health.
Applications responsive to this FOA are expected to:
- Propose two research projects that synergize with each other, which are each, separately, as well as in combination, expected to make significant contributions to the design of a future clinical trial of one or more of the product(s) studied. The choice of specific aims should be justified based on variables likely to have the greatest influence on the design, information yield, and/or health-related outcomes of a future clinical trial. Examples of appropriate specific aims for the BDSRC research projects include, but are not limited to, research to (further) understand the causal, molecular bases for bioactivity, outcome relevance of measures of proximal bioactivity (at the immediate in vivo product target(s)), the causal, molecular bases for any significant inter-individual differences in response to the product(s) to be studied, determination of optimal product formulation, timing and time course of delivery, dose, or outcome measures.
- Provide at least two independent lines of evidence for a reproducible and clinically significant biological effect of the product to be studied, when orally delivered at safe levels.
- Propose a Botanical Core, which will be responsible to ensure product integrity and availability in sufficient quantity, of materials used by both research projects and any collaborating projects within the CARBON.2 Consortium, and to advance understanding of the chemistry of the product(s), including describing specific aims expected to rigorously assess the potential presence in the product of additional bioactives, which may synergize with or add to the proposed (known) bioactives, counteract them, or have quite different bioactivities , including in vivo targets not previously noted for the product studied.. Such aims may include unbiased screening platforms, as well as a variety of other approaches, as appropriate.
- Clearly describe the governance and organizational structure of the BDSRC. This should include communication plans, a description of the Internal Steering Committee, processes for making decisions on scientific direction in conjunction with the External Advisory Committee, and procedures for resolving conflicts. An Administrative Core may be included, but is not required. The roles and administrative, technical, and scientific responsibilities for the BDSRC PI(s), Project and Core Leaders, should be clearly delineated.
- Describe plans for obtaining funds (or utilizing existing resources) to provide training and career development opportunities in trans-disciplinary approaches to understand the biological and/or behavioral effects of complex botanicals, for graduate students and post-doctoral fellows.
- Outline areas in which BDSRC investigator interactions with other components of the CARBON.2 Consortium (to be awarded at approximately the same time as the BDSRC), might extend the impact of the BDSRC research, including through a pilot project component, to be described at a later date. Such collaborations are expected to include, where appropriate and productive, collaborative demonstration projects with the concurrently awarded Centers for Natural Product Technology, Methodology and Productivity Optimization and participation in meetings, including, but not limited, to the annual meetings of the CARBON.2 Consortium investigators. Specific potential collaborators should NOT be described in the BDSRC applications.
While the BDSRC may include human subjects research designated as clinical research, the awards we expect to make in 2020 will not support clinical trials of efficacy nor tests of effectiveness. Future clinical trials building on the BDSRC findings may be supported in a variety of ways, including, but not limited to, FOAs such as NCCIH’s PAR-17-172 and PAR-17-174.
The research supported under this FOA is intended to make a significant contribution to the optimal design of a future clinical trial of the product studied. It should have the potential to indicate that further studies are unlikely to detect significant health benefit. In addition, the BDSRC are expected to provide a context for training of the next generation of trans-disciplinary researchers focused on the effects of complex, orally consumed botanicals on human health.
Botanicals of interest
Terrestrial plants or macroscopic fungi (and products derived from them) are included within the purview of this FOA. Projects may focus on isolated bioactive plant constituents other than essential nutrients where required for elucidation of mechanisms of action or other experiments that are within scope of this FOA. Applications to conduct research on purified entities found in, or synthetic compounds derived from botanical sources will be considered only where such research is necessary to elucidate the mechanisms of action or activities of the complex botanical. This FOA supports research on traditional herbal medicines as well as on foods of plant origin that are proposed to contain bioactivities beyond basic nutrients. While optimization of product formulation based on the results of the proposed research are appropriate for this FOA, applications focused on methods to improve large scale production of individual natural products or their derivatives, or on tools to modify natural products for the purpose of improving potency, will be considered unresponsive and will not be reviewed.
Funding Information
Estimated Total Funding $3.6 million total costs
Expected Number of Awards 3
Estimated Award Ceiling $1.2 million total costs
Primary CFDA Numbers 93.321, 93.213
Anticipated Eligible Organizations
Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
City or township governments
Special district governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization
Applications are not being solicited at this time.
Inquiries
Please direct all inquiries to:
Barbara C. Sorkin, PhD
Office of Dietary Supplements
sorkinb@od.nih.gov
D. Craig Hopp, Ph.D.
National Center for Complmentary and Integrative Health (NCCIH)
301-496-5825
hoppdc@mail.nih.gov
and Human Services (HHS)
