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

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

In 2012, the National Institutes of Health (NIH) Common Fund developed a comprehensive program to increase the national capacity in metabolomics for understanding human health and combating disease (http://commonfund.nih.gov/Metabolomics/). The first stage of the Common Fund Metabolomics Program (2012-2018) supported a Data Repository and Coordinating Center (DRCC) to house and promote sharing of public metabolomic data; 6 Regional Comprehensive Metabolomics Resource Cores (RCMRC) to increase access to affordable, high-quality metabolomic analyses and expert collaborative opportunities; technology development research grants to address technical roadblocks impeding the use of metabolomics; a variety of training support mechanisms to increase the cadre of investigators trained in metabolomics; and metabolite standard synthesis contracts to increase the repertoire of reference metabolites for validation of chemical identity.

Investment in this technology from the Common Fund and from research institutions across the United States has enhanced the ability of the biomedical research community to generate and analyze high quality metabolomic data. This success is reflected in the large number of recent biomedical research publications employing metabolomic approaches and in the substantial increase in the number of funded NIH research grants using metabolomics. Recent published examples illustrate how metabolomics can provide functional read-outs for genomic or transcriptomic changes and reveal novel biological understanding with high clinical impact. However, despite the enhanced infrastructure and widespread use of metabolomics, challenges remain in generating and utilizing metabolomic data. To overcome these challenges the community needs:

• An enduring public repository for metabolomic data with capacity for large, well-annotated basic and clinical datasets; searchable and user-friendly access for re-analysis; and community agreement and adoption of data sharing policies.
• Novel approaches to dramatically facilitate chemical identification of unknown spectral features from metabolomic analyses.
• Open-source, generalizable, and scalable bioinformatics tools for scientists with limited expertise in bioinformatics to use for metabolomic data analysis and biological interpretation, including ability to integrate with other -omics data.
• Identification and adoption of best practices in metabolomic study design, sample handling, platform choice, quality control, and data harmonization to ensure accuracy and reproducibility of metabolomic data.

Accordingly, the goal of the second stage of the Common Fund Metabolomics Program is to realize the potential of metabolomics to inform basic, translational and clinical research by 1) establishing an enduring national public repository for metabolomic data; 2) overcoming technical hurdles in analyzing and interpreting metabolomics data, including the ability to determine metabolite identities; and 3) developing consensus for, and promoting adoption of, best practices and guidelines to promote accuracy, reproducibility, and re-analysis of metabolomics data in collaboration with the national and international communities. Four initiatives will be supported: 1) a National Metabolomics Data Repository (NMDR); 2) Compound Identification Development Cores (CIDC); 3) Metabolomic Data Analysis and Interpretation Tools; and 4) a Stakeholders Engagement and Program Coordination Center (SEPCC). The different funded components will work together as a consortium to accomplish their specific goals and reach out to the greater metabolomics community to identify additional hurdles impeding the use of metabolomics in biomedical and translational research, and develop strategies to overcome them.

The goal of this cooperative agreement Funding Opportunity Announcement (FOA) is to address key challenges in analyzing and interpreting metabolomics data by developing novel tools to facilitate metabolomics data analysis and interpretation. Specifically, successful awardees will develop new or enhanced computational approaches or tools that facilitate metabolomics data analysis, interpretation, and integration. Generalizable, scalable, and portable solutions appropriate for scientists with limited expertise in informatics are particularly encouraged. Projects are not intended to supplement ongoing metabolomics analyses, but to provide tools for broader use by the biomedical research community.

Applicants should address defined roadblocks in metabolomics data analysis, describe the scientific gap their tool/approach is intended to address, and compare their tool/approach with currently available software/approaches. Generalizable, scalable, and portable solutions appropriate for scientists with limited expertise in informatics are particularly encouraged. Responsive applications should address one of the following topics:

• Integration of metabolite data acquired on different metabolomics technological platforms.
• Novel data analyses that better uncover relationships between diseases, metabolites and biochemical pathways.
• User-friendly metabolomics data visualization tools.
• Improved statistical methods for metabolomics data analysis.
• Integration of metabolomics data with other omics data to test specific biomedical questions or elucidate biochemical pathways/interactions.
• Tools to interpret, visualize, and/or integrate data obtained through stable isotope- resolved, kinetic, or flux analysis.
• Tools to improve rigor and reproducibility within or across platforms.
• Approaches to analyze metabolic imaging data.

• Tool performance should be validated with real metabolomics data in collaboration with an established metabolomics researcher. The original source code for any software and algorithms developed must be made available and accessible.
• All projects must adhere to the FAIR (findable, accessible, interoperable, and re-useable) principles, where appropriate.
• Projects may address any stage of the data processing, analysis, and interpretation pipeline, except for compound identification, which is specifically addressed in RFA-RM-17-013, Compound Identification Development Centers.

All grantees are expected to work collaboratively with other members of the Common Fund Metabolomics Consortium. PD(s)/PI(s) and appropriate staff are also expected to attend semi-annual Consortium program meetings. This includes the Annual Program Meeting and one additional in-person Steering Committee (SC) meeting per year. For budget planning purposes, it can be assumed these will be 2-day domestic meetings.

All applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA, and the Metabolomics Program. A technical assistance teleconference will be held for potential applicants. NIH staff will be available to answer questions related to this and companion FOAs. Time, date, and dial in information for the call will be announced in an NIH Guide Notice and will be posted on the Common Fund Metabolomics website: https://commonfund.nih.gov/metabolomics.

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 in response to 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 - Including the NIH Intramural Program
• 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 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) (formerly CCR) 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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).

Buttons to access the online ASSIST system or to download application forms 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, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Krista Zanetti, PhD
Telephone: 240-276-6843
Fax: 240-276-7920
Email: zanettik@mail.nih.gov

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.

When appropriate, awardees will be expected to collaborate, share novel approaches, and share both positive and negative results that would help guide the research and development activities of other Consortium awardees. These activities will be facilitated by regular meetings of the Metabolomics Consortium. Budgets should include cost for travel to one annual meeting of the Metabolomics Consortium in each of the proposed project years, and one additional face-to-face Steering Committee meeting annually, both held domestically, in addition to other anticipated travel associated with the research.

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:

• All projects should include an appropriate validation plan that uses real metabolomics data and identifies participating metabolomics collaborators. Comparison to existing approaches, if available, should be included in that plan.
• Analytical tool development projects should also include a plan for testing usability and reproducibility of their product by scientists in the greater biomedical research community. Use of existing metabolomics data from the National Metabolomics Data Repository (see RFA-RM-17-011) in testing is encouraged.
• Awardees must confirm their willingness to work in consultation with the Stakeholders Engagement and Program Coordination Center and the National Metabolomics Data Repository (see companion FOAs RFA-RM-17-014 and RFA-RM-17-011) to make their tools accessible through the consortium web portal for efficient use by researchers to analyze both their own data and data stored in the National Metabolomics Data Repository.

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.
• Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the Metabolomics Program and approved by NIH staff. The primary goal of the Metabolomics Program is to realize the potential of metabolomics to inform basic, translational and clinical research. Thus, the development of policies, methods, and standards for sharing is critically important. The NIH expects that the awardees, through the Metabolomics SC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.
• Specific Plan for Data Sharing: All grantees of the Metabolomics Program will be subject to and expected to abide by data sharing standards developed by the Metabolomics Steering Committee consistent with achieving the goals of this Program. This will include upload of metabolomics data in the National Metabolomics Data Repository, when applicable, or in other public access databases in cases where the National Metabolomics Data Repository is not a suitable option for the type of data being generated.
• Specific Plan for Sharing Analytical Tools and Software: A software dissemination plan, with appropriate timelines, is expected in applications that are developing software. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. A dissemination plan guided by the following principles is thought to promote the largest impact:
• The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
• The terms of software availability should include the ability of researchers outside the Center and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with the Center.
• To further enhance the potential impact of their software, applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution. Accordingly, awardees are encouraged to manage and disseminate their source code through an open revision control and source code management system such as GitHub.
• Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.
  
  
• Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov)
• Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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 there a strong scientific premise for the project? 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? Will the project advance the field of metabolomics by overcoming current hurdles in data analysis and integration, and provide approaches easily adoptable by the biomedical research community?

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? Has the investigator demonstrated awareness of the challenges of analyzing and interpreting metabolomics data? Does the investigator demonstrate a clear understanding of the biomedical questions that can be addressed through metabolomics? Does the investigative team have sufficient computational experience?

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? Will the proposed tool or algorithm simplify the analysis, interpretation, or integration of metabolomics data?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? Can the approaches be easily adapted or utilized by the broader metabolomics community? Is there a plan for testing the tool or algorithm on a data set distinct from the dataset used to develop the tool or algorithm? Are plans in place for testing the usability of the tool by the intended audience?

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 children, 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? Does the institution have appropriate computational core facilities for the proposed project?

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.

For research that involves human subjects but does not involve one of the six 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 six 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 children 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) and (4) Analytical Tool/Software Sharing Plan.

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 the Center for Scientific Review, 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 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 National Cancer Advisory 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.
• Compliance with resource sharing policies.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, 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 NIH 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.

Definitions

NIH Metabolomics Working Group (WG): Consists of NIH programmatic staff from multiple Institutes and Centers of the NIH. This group will be primarily responsible for the stewardship of the Common Fund Metabolomics Program.

Steering Committee (SC): The SC will provide coordination activities for the Common Fund Metabolomics Program. PD(s)/PI(s) of each of the Program components and the NIH Metabolomics WG members will serve on the SC.

External Scientific Consultants (ESCs): The NIH Metabolomics WG will recruit outside experts (non-awardees) of relevance to the Metabolomics Program to provide advice to NIH. The NIH Metabolomics WG may solicit from the ESCs input on progress made by individual awardees, progress made towards the overall goals of Metabolomics Program, and any changes in scope or governance that might make the Program more effective and useful to the biomedical community.

Metabolomics Consortium: The Metabolomics Consortium will be composed of awardees from the four Common Fund Metabolomics Program initiatives, the NIH Metabolomics WG, and other scientists and groups the SC agrees to include within the Consortium. The Consortium structure is meant to enable the overall goals of the Metabolomics Program.

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

• Determining research approaches, designing protocols, setting project milestones, and ensuring scientific rigor.
• Conducting the scientific research in the project, reporting progress and milestones or objectives to NIH staff, reporting results to the scientific community, and disseminating approaches, methods, and tools broadly.
• Coordinating and cooperating with other components of the Consortium and with NIH staff to maximize impact of the Metabolomics Program and meet Program goals and objectives.
• Agreeing to the governance of the Metabolomics Consortium through the SC and the NIH Metabolomics WG, including accepting approved recommendations from the ESCs.
• Updating goals and milestones at the time of award and providing summaries of progress toward those goals at least yearly, as requested by NIH. The milestones will be reviewed annually (and at other times, if necessary), and new milestones will be negotiated, as needed by working with the NIH Metabolomics WG and Project Scientists as appropriate.
• Actively participating as a voting member in the Metabolomics SC, including attending both in-person and teleconference meetings, and participating in collaborative activities and subcommittees. There will be an Annual Program Meeting, and at least one other in-person SC meeting held each year. PD(s)/PI(s) are expected to budget appropriately for travel to these meetings.
• Contributing to, adhering to, and implementing the goals, priorities, procedures, and policies agreed upon by the Steering Committee. This includes, but is not limited to, policies pertaining to intellectual property, data and software release, publication of Metabolomics Consortium papers, quality control metrics, standardization, metadata requirements, and public copyright licensing that are recommended by the Metabolomics SC and approved by the NIH Metabolomics WG, as well as applicable NIH policies, laws, and regulations. This also includes protection of human subjects, where applicable.
• Ensuring that data are deposited in a timely manner in the appropriate public databases as agreed upon by the Metabolomics SC and approved by the NIH Metabolomics WG. Ensuring that software and other tools and resources developed as part of this project are made publicly available per NIH and Consortium policies, and that results of the project are published in a timely manner.
• Being prepared for any administrative site visits by NIH staff, as determined the NIH Metabolomics WG.
• Agreeing to participate in the collaborative activities of the Consortium, and agreeing not to disclose confidential information obtained from other members of the Metabolomics Consortium.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

NIH Program Officer

• A NIH Program Officer (PO) will provide the standard programmatic oversight and stewardship of the projects, including review of pre-award and award documents/requirements, review of progress reports and budgets, and any other programmatic issues that may arise.
• The PO has the option to recommend, following consultation with the NIH Metabolomics WG, the withholding or reduction of support from any project that substantially fails to achieve its goals according to the milestones agreed to at the time of the award. NIH also reserves the right to redistribute funding within the Metabolomics Common Fund Program to take advantage of unforeseen significant advances. NIH also reserves the right to withhold funding or curtail an award in the event of: (a) Substantive changes in the project; (b) failure to deposit data or reagents in accordance with approved Sharing Plans; or (c) ethical or conflict of interest issues.

NIH Project Scientists

• The NIH Project Scientist will serve as the contact point for all facets of the scientific interaction with the awardee. As required for the coordination of activities and to expedite progress, NIH may designate additional NIH staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist(s) or Analyst, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.
• The NIH Project Scientist will be a full participant of the Steering Committee (see below) and, if applicable, subcommittees that oversee the data analysis.
• The NIH Project Scientist(s) will serve as a resource with respect to other ongoing NIH activities that may be relevant to the study to facilitate compatibility with the NIH missions and avoid unnecessary duplication of effort.
• The NIH Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research activity or in reviewing procedures for assessing data quality and study performance monitoring.

Other NIH Program Staff

• May serve on the SC as needed to assist in developing operating guidelines and consistent policies for dealing with situations that require coordinated actions.
• Will review and approve, in consultation with the ESCs (as needed), recommendations and plans provided by the SC for collaborative activities amongst Metabolomics awardees or outside groups.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop Consortium policies and meet Program goals. The awardees, the PSs, and other designated NIH Staff will participate in the annual in-person SC meeting and scheduled conference calls and share information on data resources, methodologies, analytical tools, as well as data and preliminary results. ESCs will attend the Annual Meeting. Other government staff may attend the SC meetings as necessary.

The Metabolomics SC will have responsibilities in the following areas:

• Serving as the primary governing body of the Consortium. SC membership will include the PI(s) of each Project (limited to one vote for a Project with multiple PIs) and NIH staff appointed by the NIH Metabolomics WG (with NIH staff having only a single vote). The Metabolomics SC Chair will be selected by the SC, with NIH approval, and drawn from the individual project PIs. The Metabolomics SC may add additional, non-voting, members, as needed.
• Working with the NMDR Governing Board to oversee implementation of data repository and data sharing policies.
• Discussing important issues relevant to the general metabolomics community.
• Evaluating collaborative activities.
• Coordinating with SEPCC on the implementation of recommendations from SC, NIH, or ESC.
• Participating in subcommittees or working groups convened by SEPCC as needed to address particular issues. These subcommittees will include representatives from the Metabolomics Consortium and the NIH and possibly other experts. While these groups will be managed by SEPCC, the SC will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees. It is anticipated that multiple subcommittees may need to be formed, for example, to address topics such as data sharing, promotion and outreach, and other key issues.
• The SC may choose to open Consortium membership to collaborators not funded through the Metabolomics Program, provided that such members agree to abide by policies enacted by the SC. The SC may generate additional conditions that apply to non-awardee members of the Consortium. Under direction of the SC, NIH staff and all awardees will be responsible for outreach. This includes advertising Program resources (including the web portal, data repository, data analysis tools, and protocols) to potential users in both the public and private sectors. Outreach will include providing letters of support in applications proposing to use Program-generated resources, including data from the National Metabolomics Data Repository.

External Scientific Consultants (ESCs):

• The ESCs will provide input and advice to the NIH Metabolomics WG. This could include reviewing and evaluating the progress of the entire Metabolomics Program or individual awardees as well as recommending changes in priorities for the Program based on scientific advances within and outside of the Consortium. The ESCs will be senior, scientific experts who are not directly involved in the activities of the Metabolomics Program. NIH will appoint the ESCs. The NIH Metabolomics WG and other NIH staff may attend executive meetings with the ESCs.
• The ESCs will meet at least once a year in conjunction with a meeting of the Metabolomics Consortium. The ESCs may also meet by phone or web at others times of the year, as needed.
• Annually, the ESCs will provide assessments to the NIH of the progress of the Metabolomics Consortium and will present recommendations regarding any changes in the Program as necessary. The assessments and recommendations will be provided through the Metabolomics WG to the Director of the Office of Strategic Coordination, NIH.

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 will be convened. The panel will have three members: a designee of the SC 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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Krista Zanetti, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6843
Email: zanettik@mail.nih.gov

Mark Caprara, PhD
Center for Scientific Review (CSR)
Telephone: 301-613-5228
Email: capraramg@csr.nih.gov

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email: dmitchum@mail.nih.gov

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.