It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The exponential increase in the creation of scientific data over the previous two decades has led to the appreciation for the need to properly archive and share those data with the broader scientific community. In 2016, an international collection of authors published an article in Nature (DOI: 10.1038/sdata.2016.18) proposing scientific data should be Findable, Accessible, Interoperable, and Reusable (FAIR). The benefits of FAIR data are widely acknowledged and accepted but making this a reality for all types of data will take considerable effort.

Natural products research is an inherently multi-disciplinary enterprise with a rich history. The isolation, structure elucidation, and biological characterization of an individual compound can sometimes span many years. As such, the methodological details used to characterize the compounds become extremely important. The methods section of most manuscripts describing the discovery and characterization of a natural product contains insufficient information to allow others to reproduce that discovery. Some important details are glossed over with the ubiquitous phrase as previously reported with a chain of references between the reader and the primary data. For some types of data, such as x-ray crystallographic data or biosynthetic gene cluster sequences, there are established procedures and repositories to share and report that data. For others, such as mass spectrometry (MS) there are emerging resources and standards. However, for nuclear magnetic resonance (NMR) data, there currently is no consensus on the platform or format for sharing. As such, much work is needed to bring natural products data into compliance with the FAIR principles.

NMR is an essential tool in natural products research, and yet, currently there is no widely accepted platform to share these data among the research community. Multiple attempts have been made to create such a repository, but none of them have reached wide acceptance. For the most part, NMR data are only available for most natural products as a collection of peak tables and perhaps as a low resolution PDF image in journal articles and supplemental information. Nearly all raw NMR data are housed locally in individual labs and academic institutions. As hardware and software platforms change over time, much of these data is lost or very difficult to access. The tools exist currently to allow sharing of raw NMR data. What is needed is a concerted effort to unite the natural products community around a common data repository and shared standards for reporting of raw NMR data.

Objectives

This FOA is being released in conjunction with the Center for Natural Product Technology, Methodology and Productivity Optimization (NP-TEMPO), and the Botanical Dietary Supplements Research Centers Program. Collectively, the awards under these FOAs constitute the NIH Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program. Applicants applying under this NP-NODE FOA are encouraged to collaborate, where appropriate, with the NP-TEMPO, the Botanical Dietary Supplement Research Centers, and other NCCIH, ODS, and NIH supported grantees as well as other national and international researchers.

The main objective of the NP-NODE is to create a data repository for sharing of raw NMR data. Ultimately, the NP-NODE aims to establish a powerful resource that will house the majority of the world s natural products NMR data in a format that allows facile cross-linking with other data repositories. This requires the database to be structured and annotated in such a way as to allow and support linking with other data repositories that contain different types of data on the same compounds. Parallel development of appropriate tools will permit the rapid interrogation of NMR spectra within the data repository. The NP-NODE should include basic tools to facilitate search and comparison of spectral data and associated structures while also allowing for other groups to develop additional tools using the deposited data. To accomplish this, the grantee will need to establish the platform for the repository and collaborate widely with the natural products community to develop consensus on the raw data format and minimum data standards and metadata for the repository. Additionally, the grantee is expected to actively solicit through various channels deposition of data to populate the repository. Importantly, the grantee will also need to develop a plan for how deposited data are to be curated. Ultimately, a plan for the long-term viability for this repository will be required. Therefore, applicants should begin to consider models for this, but it is not expected that they will be in place in the timeframe of this initial phase of the project.

The NMR data repository is the cornerstone of what is expected to be a larger effort which seeks to establish data sharing standards for the natural products research community. For the purposes of this FOA, natural products include vitamins, minerals, and probiotics as well as small molecules derived from plants, fungi, bacteria, marine organisms or animals. They may also exist along a spectrum of complexity from crude extracts to purified constituents. The NP-NODE will also coordinate broadly with the natural products research community to establish good research practices related to reporting and sharing of all natural products related research data. The conversation should build understanding of, and agreement on, the importance of abiding by the FAIR data principles.

NCCIH will also utilize the NP-NODE to help address the principles of the NCCIH Product Integrity Policy. This policy establishes standards regarding the quality control data expected of any natural product to be used in an NCCIH funded grant. It is expected that the NP-NODE will assist NCCIH and potential NCCIH grantees prior to award to evaluate data submitted in response to this policy. This will include recommendations about additional pieces of data that would help fully address the requirements of the policy as well as potential collaborators in the form of companies, contract labs, or academic groups that could help acquire that information. Importantly, the NP-NODE is not expected to provide that data directly except in special cases. Furthermore, it is not expected that the NP-NODE will have expertise on hand to directly address the full range of products that are within the purview of NCCIH. Rather, the NP-NODE will serve an advisory function to assist prospective NCCIH grantees in finding resources to satisfy the requirements of the policy.

At a minimum, the NP-NODE is expected to have the following capabilities:

• A cloud platform to house raw NMR data;
• A user-friendly interface to allow for upload, download, search and analysis of NMR data in the repository;
• Tools and consensus standards to facilitate widespread utilization of the repository;
• Encouragement of additional tools from the natural products research community that leverage the repository data
• Ability to coordinate information standards across the natural products research community that are compatible with existing standards, such as herbal CONSORT, ARRIVE, NCCIH Product Integrity, etc.
• The ability to assist NCCIH and ODS with implementation of the NCCIH Product Integrity Policy

Developing a Platform

If an NMR Data Repository is to become widely accepted and utilized by the natural products research community it must be housed in such a way that it can accommodate the types of data that need to be deposited. At a minimum, this should include raw 1D and 2D NMR data files. Proton and carbon spectra are by far the most common nuclei, but the repository should be constructed in a way that it could expand to include NMR data for fluorine, nitrogen, phosphorous, etc. At the outset, the barrier for depositing data should be very low until broad agreements can be reached regarding a universal format. There are existing tools that can read the various vendor formats and transform the spectra into useable data. The NP-NODE should expect to handle much of the data curation and extraction effort for deposited spectra in the early stages of development.

The data repository must be capable of scaling as the volume of data and tools expands. Ideally, the repository will grow to include tens of thousands of NMR spectra. The repository must be robust enough to handle that volume, and there must be a reasonable expectation that it will exist long into the future and keep pace with advance in bioinformatic computing. For this reason, a cloud-based format is particularly attractive. It is expected that the repository will integrate future NIH efforts related to data stewardship. As with any resource, the NP-NODE must consider how the repository will be sustained over time. Availability of continuous NIH support cannot be assumed. Therefore, applicants should describe possible models of sustainability that could be considered in the event NIH support ends. The applicant must demonstrate a deep understanding of the barriers that have prevented the widespread utilization of prior attempts at creating an NMR repository. A clear strategy must be presented for how these barriers will be overcome with the current effort.

All deposited data must receive a unique digital object identifier to allow easy retrieval, citation, and tracking. Furthermore, the data should be annotated in such a way that it allows for seamless integration with other data repositories (e.g. structures stored as SMILES strings). The NP-NODE must be a powerful resource on its own, but also extend and amplify its utility through linking with other data repositories such as PubChem and the various MS data repositories. The NP-NODE should have a well-established plan for redundant storage of the data to ensure its security and longevity.

The NP-NODE will need an interface to allow users to interact with the data. The applicant must demonstrate appropriate expertise and prior experience on their team with developing user-friendly interfaces. The website should provide clear options for importing or exporting data. There should be preliminary tools to allow searching of the repository based on combinations of text, structural and/or spectral features. This should include the ability to search on full or partial structure/spectrum. Importantly, it must be possible to access the entire repository to allow researchers to visually see how their data relates to all other spectra in the repository.

Creating Tools and Standards

In order for the deposited raw NMR data to be of any value to the research community there must be tools that allow that data to be searched, compared, and otherwise manipulated. Basic tools that allow for transformation and visualization of individual spectra and simple search functionality for structural or spectral features should be deployed immediately. Longer term, the NP-NODE should work closely with tool developers to encourage design and deployment of more sophisticated tools that permit mining of the entire data set simultaneously to uncover patterns and clustering of spectral and structural features in ways that are becoming common with mass spectrometry data. For this to be possible the interface should be structured in a way that allows the entire repository of spectra to be retrieved by individual users.

Procedures for uploading and downloading of data should be established and well described. Importantly, deposition of data must be as straightforward as possible to minimize the barrier for researchers to use the resource. This will have to also be balanced against the need to create a file format that contains sufficient information. To achieve that balance, the NP-NODE will need to work closely with all stakeholders to reach a consensus. Applicants should clearly describe how they will manage the competing priorities of rapid deployment and consensus building. Furthermore, the NP-NODE should allocate appropriate resources to allow for training of new users or on new tools as they come online.

For the NP-NODE to be successful, it will require interaction with a wide cross section of the natural products research community. Consensus will need to be reached regarding a variety of repository features. One of the first efforts in this regard will be on the format for the raw NMR data. There are a number of existing options including NMReData, nmrML, and NMR-STAR to name a few. Very early in the development of the repository, an agreement will have to be reached about how data will be deposited in the repository. Use of an existing data format is not a strict requirement as long as there is widespread agreement from diverse segments of the stakeholder community. Unanimity of opinions likely will not be reached on this topic, but the final decision must be the result of a dialogue with stakeholders to clearly understand the pros and cons of the various options. In parallel to the decision regarding data format is agreement regarding the metadata to be included for each data submission. In addition to the basic experimental NMR acquisition parameters, this could include important details such as the producing organism, collection coordinates, extraction and purification procedures and perhaps other information that would allow future researchers to reproduce the data. As the repository is developed, the NP-NODE also must actively encourage labs from around the world to deposit their NMR data in the repository. This might also include communication with journal editors about current or future policies related to sharing of NMR data.

Broad Coordination

Extending beyond the NMR data repository, the NP-NODE is expected to engage the broader natural products research community in a conversation about ways to strengthen the rigor and reproducibility of the overall research enterprise in this field. It is expected that the NP-NODE will work closely with the other components of the CARBON program in this effort. In part, this will entail education regarding the FAIR data principles. Incomplete reporting of experimental details is an ongoing problem across the scientific landscape. The natural products community has specific challenges associated with sufficiently documenting the methodology associated with the collection, purification, and chemical characterization of compounds. The NP-NODE is expected to solicit and gather input to help make recommendations, if not set standards, regarding how to collect and report such data to meet the rigor and reproducibility criteria set forth by NIH and further codified in the FAIR data principles. Again, interaction with journal editors may be helpful in establishing and enforcing these recommendations.

As part of this broader coordination effort, NCCIH will utilize the NP-NODE to help implement the principles of the NCCIH Product Integrity Policy as described above. The number of applicants that are subject to this policy varies substantially throughout the year and across years, but ranges typically between 10 30 per year.

Structure and Governance

As outlined above, the NP-NODE has three major components, each of which contains a number of sub-elements and include overlap with each other in places. A majority of NP-NODE activity (~65%) will be devoted to the NMR data repository. Of the remaining resources, ~25% will be devoted to the larger outreach and coordination efforts around implementation of the FAIR data principles across all aspects of natural products research. The remaining ~10% of NP-NODE activity will involve consultation on the NCCIH Product Integrity Policy.

The NP-NODE, in collaboration with NIH staff, will set annual milestones to ensure timely completion of all project goals. The milestones should establish clear metrics such that the degree to which they are achieved can be quantified. To monitor progress on those milestones, the NP-NODE will communicate frequently with NCCIH staff in the form of regularly scheduled phone calls. Furthermore, the NP-NODE should include funds in their budget to attend the annual CARBON program meeting. Applicants should propose milestones for expected accomplishments in each year of the project.

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

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

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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)

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)
• 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 Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• o 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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.

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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 SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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. 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 NOT-OD-11-101).

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Martina Schmidt, Ph.D.
Telephone: 301-594-3456
Fax: 301-480-2419
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy

Platform and Interface: Applicants should describe their strategy for choosing a cloud-based platform, including the measures that will be used to ensure the security and longevity of the deposited data. The application should include detailed description of how data will be curated. If the process will evolve over time then describe the plans to maintain integrity of the data. The platform must be scalable to handle anticipated growth of the repository for the duration of the funding cycle and beyond. Furthermore, the portability of the proposed software platform to multiple cloud service providers should also be discussed. Applicants should describe the features of the planned interface and any relevant experience with prior website development.

Tools and Standards: Describe the basic anticipated functionality of the resource. This should include anticipated procedures for the upload and download of raw NMR data. Anticipate when different tools will come online for searching, comparing, and manipulating of deposited data. Include a plan for outreach for additional tools from external groups. Provide a strategy for obtaining NMR spectra to populate the data repository. Estimate how much content will be generated by the applicant and how much will be solicited from the broader community? Describe how is this balance expected to evolve over time? Applicants are required to elaborate on how they will engage the broader NMR community to obtain input and reach consensus on the format for depositing NMR data in the repository. This outreach is expected to be an ongoing and possibly global effort that will evolve over time. Include detailed timelines for the various stages of this effort. Applicants should propose an NMR format they would utilize initially to allow population of the repository during the consensus building phase of the project. Include a concept of how the data format might change over time. It is expected that the consensus building efforts could take several years. How will this data be updated as formats evolve?

Broad Coordination: Describe an outreach strategy to both promote awareness of FAIR data principles and solicit input on how best to apply them to the natural products research community. Elaborate on plans to engage researchers, scientific journals, and other stakeholders on what minimum information standards adequately balance the need for rigor and transparency with administrative burden. Provide a plan for prioritizing the various types of data that might be tackled including taxonomy, chromatography, bioassay, etc.

With regards to collaboration with NIH on application of the Product Integrity Policy (PIP), applicants must describe a general strategy for how they will form teams to evaluate information provided for what is expected to be a wide variety of natural products. Describe the types of expertise that exists in-house and what would need to be outsourced. These teams might include recruitment of additional expertise on an as needed basis, but applicants should not name potential collaborators from other institutions that are only anticipated to support the PIP function of the NP-NODE. It is expected that the timeline for addressing PIP requests will vary on a case by case basis, but typically should be resolved within 30 days when possible.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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

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 SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. 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

Part I. Overview Information 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 Policy on Late Application Submission.

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 SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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.

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).

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? How effective is the proposed NP-NODE at facilitating coordination and data sharing across the natural products research community? How well do they promote awareness and adoption of FAIR data principles? How well does the outreach plan unite the natural products community behind this resource? Is the data repository structured in such a way that fosters utilization? Have the applicants demonstrated a clear understanding of, and plan to overcome, the obstacles that have prevented development of a widely adopted NMR repository to date?

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? How well does the application incorporate broad expertise in natural products chemistry, bioinformatics, web interface design, and data repository development? How well does the applicant describe coordination between these disciplines?

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? Are the proposed tools likely to provide innovative ways to mine NMR data?

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?

To what extent does the proposed outreach plan engage the broader natural products research community? Does it include all relevant stakeholders? How well does the applicant describe a strategy to reach consensus on format and content of the repository? Is the strategy for choosing the platform well thought out? How well does the applicant describe strategy for populating the repository both short term and long term? Is the plan for maintaining the security of the repository, including redundant data storage, adequate? Are the proposed models for future sustainability reasonable? Are plans for the curation of the data well described? Does the applicant provide a clear understanding of the NCCIH Product Integrity Policy? Does the application describe how the repository will be structured to enable linking with other repositories containing orthogonal data? Will the imbedded tools provide for rapid interrogation of NMR spectra including basic search and compare features? Is there a clear plan for design and deployment of more sophisticated tools? Does the structure of the repository allow for scaling as the volume of data grows?

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?

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?

Are there sufficient computing resources at this institution(s) to accommodate the needs of this repository? Does the applicant have sufficient access to NMR facilities, NMR spectra, and/or a source of natural products to allow for seeding of the repository?

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.

Is the timeline for creation, deployment, and population of the repository reasonable? Do the milestones appropriately balance time to build consensus among the natural products community on important repository features with a sense of urgency to deploy a basic resource that can be used as soon as possible?

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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal 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.

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.

Not Applicable.

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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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.

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 policy and procedures, 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:

• 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.
• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

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.

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.

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. 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 FOA 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.

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: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that 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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, 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 45 CFR Part 75.205 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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 745, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement U24, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NCCIH/ODS purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining approaches, designing protocols, proposing project milestones, and conducting the work.
• Coordination and maintenance of the activities within his or her institution, with collaborating scientists, and with the NIH Project Scientist and Program Official coordinate activities including the External Advisory Committee meetings (see below).
• Incorporating relevant improvements and developments in technology over time, as appropriate.
• Interacting with the natural product community to ensure that the resources emanating from the NP-NODE continue to meet the needs of the field.
• Ensuring that the technology and/or methodology produced or assembled by the resource are made publicly available.
• If appropriate, developing the training documentation or courses to assist the scientific community in using the resources developed by this project.
• Establishing and chairing an Internal Steering Committee (ISC) to coordinate and manage the NP-NODE activities. The ISC will consist of key personnel from the NP-NODE and NIH staff, as appropriate, meeting periodically.
• Cooperating in the dissemination of the developed resource. The recipient will retain custody of and have primary rights to the data and software developed under these awards, subject to the Government rights of access consistent with current HHS, PHS and NIH policies. The NIH will have access to and may periodically review all data generated under an award. Where warranted by appropriate participation, plans for joint publication with NCCIH/ODS of pooled data and conclusions are to be developed by the PD/PI(s) and ISC, as applicable. NIH policies governing possible co-authorship of publications with NCCIH/ODS staff will apply in all cases. In general, to warrant co-authorship, NCCIH/ODS staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; and (c) preparation and authorship of pertinent manuscripts.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• Be the contact point for all facets of the scientific interaction with the recipient. As required for the coordination of activities and to expedite progress, NCCIH/ODS may designate additional staff to provide advice to the recipient on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Analyst, who will provide direct technical assistance to the recipients to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.
• Approval of annual milestones and evaluation of level of completion of milestones as reported in annual progress report.
• An NCCIH Program Official will be named in the award notice who will retain overall programmatic responsibility for the award including normal program stewardship and review of the scientific progress of the NP-NODE and the dissemination of the assembled resources to the natural products research community.
• Interacting with the PD/PI(s) on a regular basis to monitor study progress. Monitoring may include: regular communication with the PD/PI(s) and staff, periodic site visits for discussions with recipient research teams, observation of management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at ISC, External Advisory Committee, and related meetings. The NIH retains, as an option, periodic external review of progress.
• Providing advice on the management and technical performance of the projects.
• Assisting in promoting the availability of the resources developed during the course of this project to the scientific community at large.
• Helping to coordinate the work on this project with related projects. In particular, facilitating interaction between the NP-NODE and other NIH grantees that may be suitable collaborators for data deposition, format structure, or tool development.
• Convene the first meeting of and subsequently participate in the ISC that oversees study conduct. The NIH Project Scientist or designee will be a full participant and voting member of the ISC and, if applicable, subcommittees.
• Will be responsible for establishing an External Advisory Committee (EAC), in consultation with the PD/PI(s), and working with the PD/PI to coordinate regular EAC meetings. The EAC will be composed of the Project Scientist, who will serve as a voting member, and up to five external advisors with appropriate expertise to provide advice relative to the methods and objectives of the NP-NODE as well as make recommendations to NCCIH/ODS regarding the continuation to the next stage of implementation of the projects. The EAC will serve as the primary advisory body of the NP-NODE, and the Project Scientist will rely on the EAC for objective evaluation of the Program.

The EAC will:

• Monitor progress of the data repository and assess its potential impact on the field of natural products research
• Monitor the use of resources developed in the NP-NODE by other investigators
• Evaluate the effectiveness of the NP-NODE PI
• Identify problems and suggest possible solutions
• The EAC’s evaluations and recommendations, in the form of a written annual report, are to be submitted to the Project Scientist and the NP-NODE PI, and will be used by the Project Scientist and the NP-NODE PI to guide and direct the program. Subcommittees with additional ad hoc advisors may be established by the EAC as necessary in order to meet its planning, priority setting and evaluation responsibilities. Awardees generally will be expected to accept and implement the recommendations of the EAC; in those situations where implementation of the recommendations is not feasible, the NP-NODE PI must provide a thorough explanation and rationale to NCCIH/ODS. The first EAC meeting will be convened by the Awardee within three months of the award date. The EAC will then meet annually three months before the anniversary of the NP-NODE award date.

Areas of Joint Responsibility include:

• Evaluating the NP-NODE progress in meeting its goals and the research community’s needs.
• Ensuring that coordination with the natural products research community happens as needed.
• Serve as a venue for coordinating the improvement of resources through collectively evaluating new procedures, resources, and technologies.
• Establish an Internal Steering Committee (ISC). The ISC Chair will not be an NIH staff member. The ISC may add additional members. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions.
• The ISC will be composed of the PD/PI(s) and other key personnel as deemed necessary, and the NCCIH/ODS Project Scientist or designee. An initial meeting of the ISC will be convened early after award by the NCCIH/ODS Project Scientist or designee. The final structure of the Steering Committee will be established at the first meeting. The NCCIH/ODS Project Scientist or designee will have voting membership on the ISC, and as appropriate, its subcommittees. The NCCIH/ODS Project Scientist will serve as an ex officio member of the ISC. Such a committee usually will meet at least quarterly.

The ISC has primary responsibility to design research activities, establish priorities, establish and maintain quality control among recipients, review progress, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NCCIH Program Officer, and will provide periodic supplementary reports upon request.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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 $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 (currently 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 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

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: http://grants.nih.gov/support/ (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: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

D. Craig Hopp, Ph.D
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-496-5825
Email: [email protected]

Martina Schmidt, Ph.D.
Telephone: 301-594-3456
Fax: 301-480-2419
Email: [email protected]

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: [email protected]

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.

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 45 CFR Part 75.