Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Complementary and Integrative Health (NCCIH)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Dietary Supplements (ODS)

Funding Opportunity Title
Leveraging Data at Scale to Understand Natural Product Impacts on Whole Person Health (R01 Clinical Trial Not Allowed)
Activity Code

R01 Research Project Grant

Announcement Type
New
Related Notices
  • March 25, 2024- Notice of NCCIH Technical Assistance Webinar for RFA-AT-24-008. See Notice NOT-AT-24-038.
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Funding Opportunity Number (FON)
RFA-AT-24-008
Companion Funding Opportunity
None
Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)
93.213, 93.321
Funding Opportunity Purpose

This notice of funding opportunity (NOFO) will support development, adaptation, and/or applications of computational tools to aggregate and analyze orthogonal chemical and/or biological data sets related to natural products with the aim of generating novel testable hypotheses regarding their biological activity and role in the context of whole person health research.  Projects must leverage and merge multiple compatible or interoperable sources and/or types of data.  Use of artificial intelligence and machine learning approaches is encouraged. This NOFO is part of the Consortium Advancing Research on Botanicals and Other Natural Products (CARBON) Program. Other components of this Program include the Botanical Dietary Supplements Translational Research Teams (RM1) and RFA-AT-24-007 Limited Competition: Research Resource for Natural Product Nuclear Magnetic Resonance Data (R24).

Key Dates

Posted Date
March 05, 2024
Open Date (Earliest Submission Date)
May 28, 2024
Letter of Intent Due Date(s)

May 28, 2024

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
June 28, 2024 Not Applicable Not Applicable November 2024 January 2025 April 2025

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Expiration Date
June 29, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Plants, plant-derived products, and other dietary supplement-relevant natural products are widely consumed for basic nutrition, to promote health and well-being, and for medicinal purposes, worldwide and in the United States. Despite this prevalent use, many of these products have not been rigorously evaluated; the challenges of doing research on these complex materials continue to slow progress toward understanding their contributions to public health. Since 1999 the National Institutes of Health (NIH) Office of Dietary Supplements (ODS) has partnered with the National Center for Complementary and Integrative Health (NCCIH) and other NIH components to support the Botanical Research Centers Program, now a part of the Consortium Advancing Research on Botanicals and Other Natural Products (CARBON). The Centers and pilot projects of the current CARBON have addressed, for products with highly promising supporting data, gaps in knowledge of the products and their causal, molecular mechanisms of action to support the conduct and design of future highly informative clinical trials. The current CARBON has also developed a methodological pipeline using untargeted methods to generate testable hypotheses on the molecular mechanisms underlying biological effects of chemically complex natural products. The program has generated methods and resources to support utilization of and sustainable access to relevant structural and biological activity data from natural products.

One of the hallmarks of the current NCCIH strategic plan is an emphasis on how integrative approaches, many of which include multiple components, act across interconnected domains to impart health benefits.  Natural products are most often consumed in the diet or as traditional medicine as multi-component mixtures rather than as isolated components, and the activities ascribed to them span multiple biological contexts.  Some have specificity and potency at single targets. Most have more modest activity but also seem to act pleiotropically across many targets.  Additionally, there is a growing understanding about the reciprocal relationship between natural products and the gut microbiome and how that relationship influences health outcomes.  These multi-component, multi-system interactions may be essential to their role in promoting whole person health.  However, it can be quite difficult to test this experimentally using traditional models. Objective 1 of the NCCIH strategic plan also recognizes “the need for methods development to support rigorous studies of complex botanical products, integrated multicomponent therapeutic systems, health restoration and resilience.”

Because of their ubiquitousness and potential health benefits, the range of scientific disciplines that include natural products research is broad.  Examples range from drug discovery to cell biology to nutrition, to epidemiology.  Consequently, scientific data related to natural products is vast and expanding every year.  The size, scope and scale of natural products data lends itself to computational approaches to link these disparate fields and data types in a way that traditional experiments alone cannot offer.  Linking and mining large natural product datasets using powerful computing tools could uncover relationships between combinations of natural products and their relationships with multiple biological systems that are not readily apparent.  This may allow for generation of new discoveries and novel hypotheses about how natural products, both individually and collectively, act across multiple biological systems to improve whole person health.

For example, some natural products have been reported to have activity against dozens of biological targets. Those same natural products may be found in a wide variety of commonly consumed foods.  Those foods may be associated with a variety of health outcomes. Yet, all this data is scattered. By aggregating this information and analyzing the millions of data points computationally, it may be possible to derive theories about how certain combinations of natural products act in concert and how the variety of biological activities attributed to them could reveal relationship between and across biological systems that would not be inferred based on analysis of the data in isolation.

Objectives  

This initiative will support transdisciplinary teams (e.g., data scientists, natural product chemists, nutritionists, clinicians) to adapt, develop and/or deploy computational approaches to generate novel hypotheses regarding the whole person health effects of natural products.  For the purposes of this initiative, whole person health includes assessment of how natural products, either in isolation or combination, shift multiple biological systems toward a healthier phenotype.  Natural products data exists across many different platforms so work may include efforts to aggregate scientific data related to natural products from multiple sources including primary literature, data repositories, electronic health records (EHRs), social media, etc.

Applications submitted in response to this NOFO may be used to generate new data, to analyze data from NIH-funded studies, or to analyze data derived from other sources, including genetic, epigenetic, molecular, proteomic, metabolomic, behavioral, clinical, social, or environmental studies, as well as data generated from EHRs. Applicants are encouraged to collaborate with investigators holding public or private data sets, to use innovative statistical strategies to link methodologically comparable datasets, or to utilize readily available public use and administrative data.  Supported efforts may include the activities necessary to accomplish analyses, such as locating, verifying, and evaluating data sets and preparing them for semantic and computational interoperability.  Any interoperable databases, standards, or software produced must be made open-source and freely available to the research community while adhering to privacy and ethics concerns.

For the purposes of this initiative natural products are defined as secondary metabolites of non-mammalian organisms (e.g., plants or microorganisms).  Primary metabolites such as amino acids, carbohydrates, fatty acids, etc. should not be the primary focus of a project but could be included as part of a more comprehensive data set.  The project could be limited to a specific class or category of natural product (e.g., polyphenols or triterpenes) or to specific health outcomes (e.g., sleep, mood, immune function, cognition) but should not be reduced to exploring the relationship between a single natural product type and single biological target/outcome.  Furthermore, projects seeking to mine data for the sole purpose of discovering novel natural products or focused on specific disease conditions are not responsive to this initiative.  Biological outcomes of interest are limited to improved resilience or indicators of whole person health (e.g., sleep, mood, immune function, cognition) that cross multiple biological systems rather than how natural products might prevent or treat specific diseases or their associated pathologies.  For the purposes of this initiative, resilience is defined as the ability to resist, adapt to, recover, or grow from a challenge or stressor.

Artificial intelligence and machine learning (AI/ML) methodology is encouraged as a way to mine the data and extract from it novel relationships between natural products and biological systems.  Projects must include more than one data type such as various omics outputs, in vitro data, in vivo data, clinical data, social media, but doesn’t necessarily need to include all relevant data types to be responsive.  Projects must justify their choices both in terms of the natural products and the data types and provide clear rationale for how the tools and approaches will lead to a broader understanding of how natural products may support overall human health.  Applicants must describe how they will identify and address data problems, such as known nomenclature issues with natural products, systematic biases, missing data, data set imbalance and blind spots in data to prevent or mitigate bias in the tools that are derived from the data.  Applicants should include strategies to test and verify any computationally generated discoveries.

Because this funding opportunity requires the combined application of deep domain knowledge of natural products and nutrition with the computational analytics of big data science, proposed projects are encouraged to involve a transdisciplinary team that applies an integrative, quantitative, computer analytics approach, including researchers trained in the fields of data science, mathematics, statistics, engineering, computer science, or bioinformatics.  Newly formed collaborations or teams to foster sharing of expertise between the fields of natural products chemistry, nutrition, and data science are encouraged.

Data sets to be included  should be sufficiently large and/or complex that “off the shelf” data analysis packages are insufficient to interrogate them appropriately to answer the questions relevant to this initiative.  Applicants must provide a rationale for the choice of data as well as a justification for why novel computational tools are necessary to address the scientific question(s) proposed.  Applicants can use publicly available or privately held data sets as long as they contain the scale and scope of data expected.  A collection of NIH supported data resources relevant to nutrition science can be found at the Nutrition Science Data and Biospecimen Resources Portal (https://dpcpsi.nih.gov/onr/onr-nutrition-science-data-and-biospecimen-resources-portal#repositories). A collection of NIH supported domain specific data repositories are also available (https://www.nlm.nih.gov/NIHbmic/domain_specific_repositories.html).

Examples of questions to be addressed in responsive projects include, but are not limited to:

  • Are the health benefits associated with a diet high in fruits and vegetables attributed, in part, to certain non-nutritive phytochemicals (e.g. polyphenols or terpenes)   consumption as part of a healthy diet?
  • Does the pleiotropic activity of some natural products produce a cumulative improvement in health that is greater than could be inferred based on their individual activities?
  • Are there novel mechanisms or microbially-derived metabolites that explain the activity of certain natural products across multiple biological systems?
  • Is the activity of common classes of natural products (e.g., polyphenols, triterpenes, carotenoids) directly and/or specifically linked to interactions with the microbiome?
  • Are there dietary natural products that exert observable effects only in combination with certain other dietary constituents or environmental exposures?
  • Is it possible to predict which components of a complex mixture are responsible for an observed outcome?
  • Is it possible to predict or infer the biological activity of a natural product mixture based on knowledge about the composition and activities of its individual components; including the possibility the composite activity may not be intuitively inferred from the individual activities?  

Activities included within responsive projects could include the following.  Applicants are encouraged to submit innovative projects that extend beyond the examples provided.

  • Integrating experimental data across spatial, temporal and organismal scales to build biologically relevant multi-scale models of natural products and whole person health.
  • Combining experimental and computational approaches—such as mathematical and computer modeling, artificial intelligence, and machine learning—to better understand complex interactions of natural products across health relevant pathways, cells and networks and their role in health promotion.
  • Improving approaches for integrating, mining, and analyzing natural product relevant health data from electronic health records, public health data sets, omics repositories, literature, and social media data, or other biomedical or social/behavioral data sets.
  • Leveraging and integrating emerging experimental data (e.g., multi-omics and other data sources) to develop more accurate computational models of how the cellular processes (e.g., metabolic, cognitive, physiologic) associated with optimal health respond to natural products.
  • Dimensionality reduction allowing visualization of high-dimensional data.
  • Developing computational models that predict which combinations of natural products in a mixture are responsible for an observed activity.
  • Improving the discoverability of natural product relevant data such that existing data becomes more compliant with FAIR data principles.

 The following examples, or others like them, would be considered non-responsive and will be administratively withdrawn without review.

  • Purely epidemiological projects looking at associations between dietary patterns or components and specific health outcomes.
  • Projects looking at omics data for the sole purpose of identifying novel compounds or biosynthetic gene clusters.
  • Projects limited to associations between specific natural products and individual cellular targets or pathways.
  • Projects focused on specific disease conditions as opposed to broader health promotion.
  • Projects that do not involve multiple data types.
  • Projects that do not primarily focus on development of computational tools.
  • Projects that do not link chemical and biological data.
  • Projects only proposing meta-analysis of clinical trial data for a particular natural product.

    

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New

The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NCCIH and partner components intend to commit an estimated total of $800,000 to fund one award.

Award Budget

Application budgets are limited to less than $500K in Direct Costs but need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Organizations)
Foreign Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Jessica McKlveen, PhD
National Center for Complementary & Integrative Health (NCCIH)  
Email: jessica.mcklveen@nih.gov 

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply - Application Guide must be followed.

CARBON Annual Meeting Costs:

  • Applications must allocate part of their budget for attending virtual and in-person meetings associated with activities of the CARBON Program, including yearly annual meetings of the full consortium.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

The research strategy should include a description of the specific data repositories to be included as sources of natural products and biomedical research data and the rationale for including them.  This should include a description of the depth and breadth of data included in those repositories and how it is relevant to the objectives of this NOFO.

The Research Strategy section must include the following elements:

Approach

  • Evidence the applicant has permission to access the data if the underlying resource is not completely open access.
  • A plan to identify and account for data problems, such as known nomenclature issues with natural products, systematic biases, missing data, data set imbalance and blind spots in data to prevent or mitigate bias in the tools that are derived from the data.
  • A strategy to conduct preliminary tests of the validity of any hypotheses generated using the data.
  • Evidence that the proposed source datasets are fit for purpose, e.g., available for use by the applicant and of sufficient size, completeness and data quality
  • Rigorous controls to demonstrate that initial models have acceptable levels of sensitivity and specificity in their outputs, and clear definitions of these levels with explanation for how they are appropriate for broader application
  • Specifically identify multiple, large data sets relevant to natural products and health outcomes associated with their consumption and evidence the data sets proposed are available and appropriate
  • A plan to account for missing and implausible data, and for the many synonyms associated with natural products

Innovation

  • How the proposed tools are novel and will lead to new hypotheses

Investigators

  • Evidence there is appropriate expertise as it relates to the type of data to be used, the outcomes being assessed, and the computational tools proposed.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

  • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
  • CARBON awardees are required to deposit data in one of the NCCIH preferred repositories (https://www.nccih.nih.gov/grants/policies/data-management-and-sharing-policy/preferred-repositories) unless there is a more appropriate domain specific repository for sharing the data type. 

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCCIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email at jessica.mcklveen@nih.gov  when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

 

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this NOFO: 

How clear is the rationale for the choice of data as well as the justification for why novel computational tools are necessary to address the scientific questions proposed?

To what extent will the proposed computational tools lead to the development of novel, testable hypotheses regarding the impact of natural products on health?

 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Specific to this NOFO: 

To what extent does the application include relevant expertise including data scientists, natural product chemists, clinicians and nutritionists?

 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this NOFO: 

To what extent are the computational tools proposed novel and likely to lead to novel hypotheses about how natural products contribute to whole person health?

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO: 

Does the application provide sufficient evidence the applicant has permission to access the data if the underlying resource is not completely open access?

To what extent does the application provide a plan to identify and account for data problems, such as known nomenclature issues with natural products, systematic biases, missing data, data set imbalance and blind spots in data to prevent or mitigate bias in the tools that are derived from the data?

How well does the application describe a strategy to conduct preliminary tests of the validity of any hypotheses generated using the data?

How strong is the evidence that the proposed source datasets are fit for purpose, e.g., available for use by the applicant and of sufficient size, completeness and data quality?

How rigorous are the controls to demonstrate that initial models have acceptable levels of sensitivity and specificity in their outputs, and to what extent are there clear definitions of these levels with explanation for how they are appropriate for broader application?

How clearly does the application describe multiple, large data sets relevant to natural products and health outcomes associated with their consumption and evidence the data sets proposed are available and appropriate?

To what extent does the application describe a plan to account for missing and implausible data, and for the many synonyms associated with natural products?

 

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

 

Not applicable

 

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

 

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

 

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

 

Not applicable

 

Not applicable

 

Not applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

 

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

 

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

 

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

 

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Complementary and Integrative Health NCCIH. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding. 

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.

HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. An applicant can review and comment on any information in the responsibility/qualification records available in SAM.gov. NIH will consider any comments by the applicant, in addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (Responsibility/Qualification in SAM.gov, formerly FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

D. Craig Hopp, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Email: hoppdc@nih.gov

Barbara C. Sorkin, Ph.D.
Co-Director, CARBON
Office of Dietary Supplements (ODS)
Email: sorkinb@mail.nih.gov


Peer Review Contact(s)

Jessica McKlveen, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)  
Email: jessica.mcklveen@nih.gov 

Financial/Grants Management Contact(s)

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Email: debbie.chen@nih.gov

Rich Bailen
Office of Dietary Supplements (ODS)
Email: bailenr@od.nih.gov


Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.