Part 1. Overview Information

Key Dates

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

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

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

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

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

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

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Research Objectives

The overall objective is to accelerate preclinical product development in tissue engineering and regenerative medicine (TE/RM), through innovation, commercialization, and clinical adoption. Supported projects may focus on therapeutics (including but not limited to drugs, biologicals, devices, adult stem-cell based therapies, and combination products), sensors, and diagnostics with an emphasis on preventing, halting, or treating damage caused by congenital defects, acute injury, chronic disease, or age-related degeneration processes. Synergies with other preclinical research efforts are encouraged.

Background

Established in 2017 through a cooperative model, the Dental, Oral, and Craniofacial Tissue Regeneration Consortium (DOCTRC) aimed to spur preclinical Investigational New Drug (IND) and Investigational Device Exemption (IDE)-enabling product research and development to support the regeneration of complex tissues within the craniofacial complex. DOCTRC provided participating investigators with support across key areas, including preclinical animal models, functional testing and prototyping, manufacturing, regulatory and quality assurance, statistical analysis, intellectual property assessment, market strategy and commercialization, and clinical trial planning. The goal was to support investigator-led interdisciplinary translational projects (ITPs) in achieving the U.S. Food and Drug Administration (FDA) product clearance for first-in-human use. ITPs have encompassed products in all regulatory domains: drugs, biologicals, devices, and combination products, as well as various tissue types related to the dental, oral, craniofacial (DOC) complex. Building on the success of DOCTRC, NIDCR is expanding this proven support model to a broader set of products and applications. The APEx consortium aims to consolidate the growing body of practical knowledge, and associated experienced innovator network, as a valuable resource for a broader community of future innovators in TE/RM. The Resource Center (RC) will support a broad spectrum of technologies and applications that align with the research objectives of participating NIH Institutes and Centers (ICs).

Program Features

This NOFO, for the APEx Resource-Related Research Projects Cooperative Agreement (U24), encourages applications from multidisciplinary groups of investigators to develop a Resource Center (RC) infrastructure to support investigator-led interdisciplinary translational projects (ITPs). The APEx consortium will focus on tissue engineering and regenerative medicine (TE/RM) applications related to tissues, organs, or technologies of interest to the participating ICs. This consortium is expected to realize the vision, research objectives, and guiding principles laid out in the strategic plans of these ICs. The consortium will consist of one RC that will collaborate with participating NIH IC(s) to support selected ITPs aligned with the research objectives of one or more ICs. The RC will provide a host of accessible training, informational services, and resources to the wider TE/RM community.

Specific requirements for the applications submitted in response to this NOFO are outlined below:

• The RC will propose an initial cohort of 4-6 projects (ITPs), with the goal of expanding support to approximately 10 ITPs over the duration of the project period.
• The RC will provide set milestones for retention and successful ‘graduation’ of the initial cohort of ITPs, as well as a process plan for selecting additional participating ITPs based on their potential to yield commercially viable products; this process will include the RC team as well as NIH consortium partners; continued participation of ITPs and support by the RC will be contingent on milestones being met.
• When one or more ITP obtain(s) FDA approval for first-in-human studies (e.g. IND/IDE), the RC will be able to consider soliciting additional ITPs at late stages of translational development.
• The RC is expected to achieve a balance of ITPs from participating RC institutions, as well as from external participants who are outside these institutions.
• Applicants are encouraged to engage participation of industrial partners in the RC and ITPs; Such partnerships are expected to accelerate the translational pipeline of the ITPs.
• The RC must propose plans for shepherding the successful exit of active ITPs to prepare them for future success, for example, by supporting plans for achieving product clearance by the FDA, new company formation, licensing and technology transfer, and/or through planned or voluntary cost-sharing in the form of additional funds raised outside the APEx Consortium. Please note that all responsive applications, whether they propose cost sharing or not, will proceed to peer review. 
• The RC must consider the affordability of products supported, and provide a plan to maximize the accessibility of these products by all populations that may benefit. The RC must propose plans to engage the broader TE/RM community through outreach within as well as beyond the RC institute community, by offering examples of practical strategies for advancing regenerative medicine research to clinical trials. Outreach efforts can be executed, for example, via an APEx website, published protocols, guidance documents, workshops, webinars, establishment of a mentoring network, social media postings, and practicums.

Applications not responsive to this NOFO

The following types of projects are not responsive to this NOFO. Applications proposing such projects will be considered non-responsive, will be withdrawn from review, and will not be considered for funding:

• Discovery research - Approaches and technologies to be pursued by the RC and the ITPs must be sufficiently mature to show significant promise in animal models or other validated human-relevant model systems, and must demonstrate feasibility and readiness to be advanced toward clinical trials on a timeline relevant to APEx support.
• Clinical trials or “first-in-human” clinical studies - Projects that have sufficiently matured to enter these clinical studies should utilize other appropriate funding mechanisms available at the participating ICs. 

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 not allowed. 

Applicant Organizations

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

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

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

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

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. 

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Page Limitations

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

For this specific NOFO, the Research Strategy section is limited to 30 pages.

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

• PD(s)/PI(s) are required to collectively contribute at least 3 person-months (25% FTE) to the Program. Increased effort is expected if the PD(s)/PI(s) lead an ITP within the RC; the amount of this increased effort should be commensurate with the specific needs of the ITP.
• Funds may be budgeted for hosting annual in-person meetings for the RC and ITPs.
• Applications funded under this NOFO are encouraged to voluntarily cost-share Federally awarded dollars with non-Federal contributions, monetary and/or in kind. Any proposed cost sharing must be clearly identified, described, and justified in the budget justification section of the application. Voluntary cost share is subject to the requirements at 2 CFR 200.306.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy

As part of the Research Strategy Section, applications must include the following:

• A description of the scientific and technical focus areas of the RC, and a discussion of how this RC supports the goals and objectives of APEx.
• Details of the organizational, administrative, and leadership structure of the RC; this should include a description of the RC leaders' history of successful collaboration and/or indicators of potential success, including but not limited to prior experience in interacting with the FDA and shepherding products through the regulatory process.
• A detailed description of the initial cohort of 4-6 ITPs, and an expansion plan to reach the approximate 10 ITPs once the RC is fully operational.
• A strong rationale for the expectation that the selected ITPs will lead to innovative new technologies, advancing the field of Tissue Engineering and Regenerative Medicine (TE/RM) within the timeframe of APEx.
• Metrics of successful outcomes for ITPs and the RC as a whole, and plans to ensure that the most promising ITPs are supported at any given time during APEx, e.g. by employing a go/no go decision-making process for continued ITP support, and through selection of additional ITPs at late stages of translational development when existing ITPs are exited from the program.
• A detailed description of expertise and resources provided by the proposed RC, including sufficiently describing relevant Standard Operating Procedures, plans for clinical protocol development, animal model support with emphasis on large animal models, plans to leverage human-based new approach methods (NAMs) to reduce reliance on animal models where feasible, synthesis, quality control, Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP) planning, scale up protocols, standardization, storage, transportation and other innovative methodological components proposed.
• A plan to ensure that the resources provided by the RC continue to be based on innovative, state-of-the-art principles.
• Current and next-generation personnel training plans in GMP/GLP manufacturing, regulatory, commercialization and marketing strategies and other components of the translational pipeline to maximize the impact of APEx.
• A plan to include ITPs both from within and outside of the participating RC institution(s).
• Strategies and projected timelines for establishing successful collaborations with industrial partners and other outside organizations.
• A communication plan for the RC, including outlining plans for successful communications between RC leadership and ITPs, as well as among scientists, clinicians, industry, regulatory and commercialization experts, NIH partners, and the FDA during preparation of first-in-human study (i.e. IND/IDE) applications by the ITPs
• Strategies for comparing safety and efficacy of the therapies, sensors, and diagnostics under development with existing “gold standards” currently available in clinical practice, as well as ensuring rigor and reproducibility of research conducted. 
• A description of the institutional facilities that will be in place to support optimal function of the RC.
• A path forward for intellectual property considerations, commercialization plans, and planned (or actualized) industry partnerships and/or voluntary cost-sharing, to support a successful shepherding of ITPs beyond the APEx program.
• A plan to maximize the accessibility and affordability of the ITPs’ products by all populations that may benefit.
• A plan for making appropriate APEx resources available beyond the home RC institute(s), such as through development and maintenance of a website and other communication tools, and plans for dissemination of knowledge gained for the broader TE/RM innovator community.

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

Other Plan(s): 

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

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed. 

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov. 

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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.

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.

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.

2. Review and Selection Process

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 policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

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

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Dental and Craniofacial Research Council. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director’s Statement of Priorities, entitled “Advancing NIH’s Mission Through a Unified Strategy.” 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Executing the research plan and goals
• Maintaining and developing the organizational and administrative structure of the RC
• Providing leadership and communication functions within the RC
• Overseeing the execution of all aspects of the projects and coordinating/overseeing research design
• Coordinating activities among collaborating ITPs, within the RC
• Ensuring compliance with mandatory regulations (including protection of human subjects)
• Providing regulatory support for submission of IND/IDE applications to the FDA to the ITPs
• Providing intellectual property and commercialization expertise to the ITPs
• Overseeing the establishment and maintenance of appropriate quality control procedures, standard operating procedures (SOPs), and other technical aspects of the RC’s function, as outlined in the Research Plan Section IV of this NOFO
• Overseeing progress of ITPs in meeting their milestones and timelines
• Promoting collaborations of the ITPs with industrial partners
• Overseeing final data analysis and interpretation and preparation of publications
• Cooperating with NIDCR and participating IC(s) programmatic, technical and administrative staff
• Administratively managing the U24 award
• Participating in monthly periodic teleconferences (as needed)
• Ensuring and overseeing the timely sharing of results, resources, methods etc. with collaborators and the scientific community
• Ensuring rigor and reproducibility of research
• Adhering to timelines and milestones and overcoming obstacles
• Tracking voluntary cost-share (if applicable)
• Timely submission of annual Research Performance Progress Reports (RPPRs); This U24 will also require additional mid-year Progress Reports

The PDs/PIs agree to accept assistance, coordination, cooperation and participation of NIDCR and participating IC staff in scientific management of the project in accordance with the terms formally and mutually agreed upon prior to the award.

Publications: The PDs/PIs will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by members of the cooperative agreement award and supported in part or in total under this Agreement. Publications or oral presentations of work performed under this Agreement are the responsibility of the PDs/PIs and will require appropriate acknowledgement of NIDCR and/or participating IC support.

The PDs/PIs are expected to maintain significant effort commitment: collectively not less than that stated in the application - at least 3 person-months (25% FTE) during the funded period of the project.

The recipient will be expected to develop and implement common, uniform standard operating procedures (SOPs) and technical formats for depositing data into public databases. Data generating methods and analysis algorithms shall be described in sufficient detail to enable duplication by other investigators.

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

A designated NIDCR Program Director(s) acting as a Project Scientist(s) (PS) will have the following responsibilities:

• Serving as a liaison/facilitator between the recipient and other government agencies
• Serving as a resource of scientific and policy information related to the goals of the awardee's research
• Providing policy assistance and feedback to the recipient as appropriate
• Facilitating coordination of project activities during the course of the project
• Assisting the recipient with access to other NIDCR-supported resources and services
• Monitoring progress of the RC as a whole and of the specific ITPs through the evaluation of semi-annual progress reports that awardees will be providing to NIDCR during the funding phase. The progress will also be monitored via regular teleconferences between the recipient and the programmatic team
• Negotiating project specific timelines and milestones with the recipient during the funding phase
• Conducting periodic site visits or discussions with recipient research teams as needed
• Facilitating interactions/collaborations between the awardees and other NIH-sponsored programs, investigators, or organizations that may contribute to the project goals
• Monitoring the adherence of the recipient to the approved resource and data sharing plans
• Monitoring rigor and reproducibility of the conducted research

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

The NIDCR will adjust funding, withhold, suspend, or terminate the support to the awardee if the team is unable to meet the negotiated milestones set forth in these Terms and Conditions of Award or the performance of the team is deemed to be significantly low that the aims will not be met within the time frame of the cooperative agreement. Continuous funding will depend upon meeting milestones negotiated for the projects.

Areas of Joint Responsibility include:

• None; all responsibilities are divided between recipients and NIH staff as described above.

Additional notes:

NIDCR will assemble an External Expert Panel to assess and evaluate progress of the RC on an annual basis and provide input to enhance performance and coordination of the RCs as appropriate. The recipient is expected to plan and budget for an annual meeting either at the NIH or at other venues to discuss the progress of their RC and ITPs.

The RC Steering Committee will direct the overall efforts of the RC and the ITPs. The steering committee will be composed at a minimum of PDs/PIs of the RC and an NIH Project Scientist serving as the representative of the NIH. All NIH staff combined have one vote on the steering committee. The RC Steering Committee will make recommendations related to all aspects of the RC development and function, and will monitor the progress of funded projects.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed. 

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

National Institute of Dental and Craniofacial Research (NIDCR)
Email: APEx-NOFO@nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

National Eye Institute (NEI)
Email: NEI_extramural@nih.gov

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Email: NIAMSGrants@nih.gov

Section VIII. Other Information

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

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