Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

The National Institute of Dental and Craniofacial Research (NIDCR) is firmly committed to facilitating clinical translation of the most promising scientific and technological advances in tissue engineering and regenerative medicine (TE/RM) to safely and efficaciously regenerate and reconstruct dental, oral and craniofacial (DOC) tissues. Toward achieving this goal, NIDCR had established a multidisciplinary DOC Tissue Regeneration Consortium (DOCTRC) that consists of three Stages. For Stage 1, one year of support was provided under RFA-DE-15-005 through the R34 Planning Grant funding mechanism to develop an overall vision, roadmap, organizational structure, operational procedures and detailed plans for establishing centralized Resource Centers (RCs).

For Stage 2, three years of support were provided under RFA-DE-17-001. The purpose of Stage 2 was to establish multidisciplinary RCs to support individual interdisciplinary translational projects (ITPs), which were charged with advancing promising strategies for regeneration and reconstruction of DOC tissues to clinical trials. Two Cooperative Agreement U24 multi-PI awards were made in 2017 to establish the two RCs. The goals of the RCs were to: 1) develop robust infrastructure for delivering uniform high-quality clinical and technical support, enhancing research capacity and providing regulatory and commercialization expertise for pre-clinical activities of the DOCTRC and 2) organize, recruit and integrate pilot ITP teams into the RCs to pursue development of specific TE/RM approaches for regeneration of functional DOC tissues, and to utilize synergistic and complementary expertise of the RCs in achieving the ITPs' objectives. To meet the demands of the accelerated translational timeline of the DOCTRC, the ITPs awards were made to those teams that have already demonstrated significant translational potential of their technical approaches. Toward the end of Stage 2, both RCs became fully-operational and each RC has successfully recruited 13-15 individual pilot ITP projects through several rounds of solicitations. These ITP projects are currently working toward achieving their technical milestones.

For Stage 3, five years of support will be provided under the current FOA: RFA-DE-19-010. The Purpose of Stage 3 will be to facilitate advancing the most promising ITPs to clinical trials. The Stage 3 infrastructure will be composed of the RCs and associated ITPs that have been initiated during Stage 2 of the DOCTRC effort. In Stage 3, the RCs will capitalize on their available clinical, scientific, industrial and regulatory and commercialization expertise, to deliver technical support, research capacity, administrative infrastructure and regulatory and commercialization support to the ITPs and guide them to complete pre-clinical studies toward initiation of clinical trials. During Stage 3, the DOCTRC will complete validation, manufacturing, and preclinical testing of the most promising TE/RM products and will develop IND/IDE applications for submission to the FDA. The outcome of the DOCTRC will be TE/RM products with their IND/IDE in place and associated clinical study protocols, as well as synthesis and manufacturing protocols ready for initiation of clinical trials.

Background

Over the years, many promising scientific and technological advances have emerged from NIDCR- and NIH- funded TE/RM research. These include scaffolds that can guide functional maturation of engineered constructs in vitro and facilitate tissue regeneration in vivo. Such scaffolds can be designed to deliver active biomolecules to cells, degrade at a pre-determined rate, control inflammatory responses, and exhibit many other useful characteristics. Further, substantial progress has been made in isolating and characterizing DOC tissue-specific stem and progenitor cells, developing functional assays for testing safety and efficacy of TE/RM products, and generating cell tracking and tissue imaging modalities for monitoring tissue regeneration in vivo. However, despite this progress, only a few TE/RM-based therapies for DOC and other tissues have reached the stage of clinical trials and commercialization.

NIDCR carried out a comprehensive analysis of the nature of obstacles interfering with TE/RM translation, and generated a plan to establish a translation-targeted DOCTRC. One of the key features to ensure the success of DOCTRC in advancing TE/RM products to the clinic is a strong alignment between specific clinical needs for DOC tissue regeneration and the available tools and technologies that have matured sufficiently in discovery research to support these particular needs. Achieving this alignment requires robust interdisciplinary and multidisciplinary partnerships among practicing clinicians, biologists, bioengineers, regulatory and industrial experts and other technical professionals. In these partnerships, there is a need for clinicians to articulate areas of clinical needs and to establish product design criteria, and, in collaboration with technical and regulatory experts to define scientific and regulatory pathway for product development.

Given a multitude of the available TE/RM-based biomaterials, scaffolds, cell sources, functional assays, animal models and other experimental tools, it is necessary to conduct side-by-side qualitative and quantitative comparisons, and to standardize, optimize and validate the available materials, cells and protocols in DOC disease and injury-relevant large animal models with respect to their safety, efficacy, and other functional outcome parameters. This work will allow the identification of those strategies that are most likely to fulfill clinical needs and succeed in clinical settings. Moreover, effective scale up, Good Manufacturing Practices (GMP) protocols and Standard Operating Procedures (SOPs), intellectual property (IP) protection and commercialization plans will be needed before the products can be effectively advanced toward clinical trials. The DOCTRC has been systematically addressing these issues during Stage 2 and will continue this pre-clinical work in Stage 3; this effort will lead to submission of IND/IDE applications to FDA for initiation of clinical trials.

Program Features  

This FOA for Stage 3 DOCTRC for Resource-Related Research Projects Cooperative Agreements (U24) encourages applications from multidisciplinary groups of investigators who developed the RCs infrastructure and recruited individual ITP pilot projects during Stage 2 of the DOCTRC effort. Because the two established RCs have already accumulated substantial expertise in functioning as technical, administrative, regulatory and commercialization support hubs for the ITP teams in Stage 2, this FOA is being issued as a Limited Competition. The Limited Competition format will ensure the most efficient utilization of this accumulated expertise.

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

• This FOA requires the applicants to engage participation of industrial partners in the ITP projects. Such partnerships are expected to accelerate the translational pipeline of the ITP projects
• The RCs are not expected to solicit a substantial number of new and additional ITPs during Stage 3, because late stage pre-clinical work commencing during stage 3 will require increased funding compared to early stage pre-clinical work conducted during stage 2. To meet these increased budgetary demands, the RCs will be required to down-select the pilot ITPs they currently support on the basis of their progress in meeting milestones in stage 2. Specific plans and criteria for down-selecting the ITPs should be clearly outlined in the applications for this FOA.   It is expected that the final set of ITPs moving forward to stage 3 will be defined at the time of the award. When  one or more  ITPs obtain IND/IDE early during stage 3, thereby freeing additional funds, the RCs will have the freedom to consider soliciting additional ITPs at late stages of translational development to assure their maturation to IND/IDE filing before the expiration of the grant period. 
• The RCs should aim to achieve a balance between the ITPs originating from the participating Institutions of the RCs and the external ITP, while striving to support the best science and those ITP projects that are most likely to succeed
• The RCs must capitalize on their unique areas of strength, and must propose specific strategies that would ensure that these unique areas of strength are complementary and benefit both RCs
• The RCs must strive to minimize redundancy and maximize synergy between the two hubs in the areas administrative, regulatory, industrial and commercialization support, and to function as a single Consortium
• The RCs must propose plans for validating key results obtained by the other RC, sharing data, protocols and other information, and coordinating functional interactions between the RCs through a common website and other means of communication
• The RCs must propose plans to engage broader TE/RM community through outreach within as well as beyond the DOC community by offering examples of practical strategies for advancing regenerative medicine research to clinical trials. This outreach can be executed via published protocols, guidance documents, workshops, webinars, social media postings and practicums  
• This FOA will not support discovery research. Approaches and technologies to be pursued by the RCs and the ITPs must be sufficiently mature to show significant promise in animal models, and must demonstrate feasibility and readiness to be advanced toward clinical trials
• This FOA will not 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 NIDCR

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

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)
• U.S. Territory or Possession

• 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

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.

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications  

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)

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

2. Content and Form of Application Submission

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

Letter of Intent  

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

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

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

The letter of intent should be sent to:

Dr. Yasaman Shirazi
Telephone: 301-594-5593
Email: shiraziy@mail.nih.gov

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

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

PD(s)/PI(s) are required to collectively provide 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 commensurate with the specific needs of the ITP.

Application funded under this FOA are strongly encouraged to match Federally awarded dollars with non-Federal contributions, monetary and/or in kind.

Applicants are required to address the following topics:

• The RCs' progress during Stage 2 and plans for transition from Stage 2 to Stage 3. Please address the following :

1. Summary of progress achieved by the RCs during Stage 2
2. Timelines and activities for achieving successful transition from Stage 2 to Stage 3
3. Leadership structure and communication plans within the RC and between the RCs in Stage 3
4. Organizational and administrative structure of the RCs in Stage 3
5. Scientific and technical focus areas of the RCs proposed for Stage 3
6. Clinical focus areas of the RCs proposed for Stage 3
7. SOPs, clinical protocol development, animal models with emphasis on large animal models, synthesis, quality control, GLP, GMP, scale up protocols, standardization, storage, transportation and other methodological components employed proposed for Stage 3
8. Side-by-side evaluations of technologies; validation, safety and efficacy assays employed proposed for Stage 3
9. Plans and criteria for down-selecting currently-funded ITPs to be taken to stage 3; timeline for this down-selection
10. Metrics of successful outcomes to Stage 3

• Overall vision of Stage 3: how the work during Stage 3 would support goals and specific objectives of DOCTRC
• Coordination of interactions between the RCs to promote collaboration, minimize redundancies, maximize synergy and take advantage of each RC's areas of strength and complementarity to benefit DOCTRC's function as a single Consortium
• Strategies and projected timelines for establishing productive collaborations with industrial partners and other outside organizations
• Communications within the RCs among scientists, clinicians, industry, regulatory and commercialization experts and the FDA during preparation of IND/IDE applications by the ITPs
• Strategies for comparing safety and efficacy of the therapies under development with existing “gold standards” currently available in clinical practice
• Strategies to ensure rigor and reproducibility of research conducted during Stage 3
• Strategies for meeting milestones and timelines and overcoming obstacles during stage 3, including go/no go decision making process
• Path forward within IP space and commercialization plans for individual ITP projects during Stage 3
• Current and next-generation personnel training during Stage 3 in GMP/GLP manufacturing, regulatory, commercialization and marketing strategies and other components of translational pipeline
• Development and maintenance of website and other communication tools during Stage 3

The following modifications also apply:

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

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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.

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.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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.

Significance  

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

Specific to this FOA:

• Is the rationale for establishing the proposed administrative and leadership infrastructure of the RCs in Stage 3 well-justified, and the proposed RCs goals and objectives adequately defined?
• Is there a high likelihood that the proposed RC infrastructure can support the ITPs?
• Will the proposed RCs infrastructure effectively support the goals and the specific objectives of the DOCTRC, to conduct pre-clinical studies leading to the submission of IND/IDE applications to FDA to develop safe, predictive and efficacious clinical strategies for regeneration of functional tissues of the human DOC complex?
• Is there sound clinical, biological and technical data to support the particular RCs infrastructure and the selection of the ITPs?
• Is there a clear statement of the focus and specific technical areas of the RCs and the ITPs in Stage 3?
• Does the application provide specific evidence that the work accomplished during stage 2 will position the RCs and the ITPs to successfully transition into Stage 3 and how this transition will be accomplished?
• Does the application clearly describe how the unique features of each RCs and complementarity between the RCs will be leveraged for minimizing areas of redundancies and maximizing areas of synergy between the RCs  for achieving the overall goals of the DOCTRC as a single Consortium?

Investigator(s)  

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

Specific to this FOA:

• Are the RCs and ITP teams appropriately qualified and well-suited for achieving the goals of DOCTRC in advancing DOC TE/RM technologies to clinical trials?
• Is there an appropriate clinical, regulatory, industrial and commercialization expertise in the teams to achieve these goals?
• Is there a history of collaboration, including collaboration during Stage 2 between the members of the teams? Do members of the teams have a proven track record in the areas to be addressed by the RCs? Will the interdisciplinary composition of the RCs and the ITPs promote productive collaborations across the Consortium?
• Are the communication and collaboration plans within the RCs adequately described? Is there an evidence of an effective leadership plan?
• Is there a plan in place to ensure proper training of the technical personnel of the RC?

Innovation  

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

Specific to this FOA:

• Are functional assays, DOC disease-relevant animal models, scale up, GLP- and GMP-grade manufacturing strategies and other technical features of the RCs based on innovative state-of-the-art principles?
• Are the overall infrastructure and organizational/managerial configuration of the RCs built on innovative principles that will enhance the RCs function?

Approach  

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

Specific to this FOA:

• Does the current RCs infrastructure effectively support the general goals and the specific objectives of the DOCTRC??
• Does the application present a detailed description of the activities to be conducted to accomplish an effective and efficient transition from Stage 2 to Stage 3?
• Does the application present a detailed description of the activities to be conducted and completed during Stage 3, including milestones, timelines and plans for overcoming obstacles and barriers?
• Is there a strategy in place for down-selecting currently-funded pilot ITPs to identify the most successful teams for stage 3 support?
• Does the application address the availability of functional assays, human disease-relevant animal models, especially large animal models, experimental protocols, quality control procedures, GLP and GMP and scale up protocols, SOPs, standardization, transportation and storage and other methodological approaches to be utilized during Stage 3?
• Are the proposed approaches, methodologies and SOPs scientifically/technically sound, and can they be executed realistically within the duration of Stage 3?
• Does the application describe procedures for side-by-side evaluations, validation of technologies, efficacy and safety assays and comparisons  with current "gold standards" of clinical practice?
•  
• Does the application present a detailed description of the interdisciplinary interactions between clinical, technical, regulatory and industrial components of the RCs?
• Does the application provide appropriate discussion of plans for interactions with FDA and preparation of IND/IDE submissions?
• Does the application address plans for interactions with industrial partners?
• Is the appropriate discussion of IP issues provided?
• Does the application include discussion of detailed milestones and timelines; are they realistic and feasible?

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

Environment  

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

• Are adequate facilities in place for optimal function of the RCs in Stage 3? 
• Are adequate plans in place for maintenance of an effective organizational structure and a communication plan, including plans for managing geographical distances, between different RCs and between the RCs and the ITPs?
• Does the application provide evidence for the availability of resources at home Institutions to support the function of the RCs during Stage 3?

Protections for Human Subjects  

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals  

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.

Biohazards  

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.

Resubmissions  

Not Applicable

Renewals  

No Applicable

Revisions  

Not Applicable

Applications from Foreign Organizations  

Not Applicable

Select Agent Research  

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).

Resource Sharing Plans  

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).

Authentication of Key Biological and/or Chemical Resources:  

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.

Budget and Period of Support  

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group convened by NIDCR, 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.

• Will receive a written critique.

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

3. Anticipated Announcement and Award Dates

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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.

2. Administrative and National Policy Requirements

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.

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.

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.

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’s purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The Program Directors/Principal Investigators 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 RCs
• Providing leadership and communication functions within the RCs and between the RCs
• Overseeing the execution of all aspects of the projects and coordinating/overseeing research design
• Coordinating activities among collaborating ITPs, within the RC and between the RCs
• 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 establishment and maintenance of appropriate quality control procedures, SOPs, and other technical aspects of the RCs' function, as outlined in the Research Plan Section IV of this FOA
• 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 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 scientific community
• Ensuring rigor and reproducibility of research
• Adhering to timelines and milestones and overcoming obstacles
• Timely submission of annual Research Performance Progress Reports (RPPRs). This U24 will require additional midyear Progress Reports

The PDs/PIs agree to accept assistance, coordination, cooperation and participation of NIDCR 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 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.

Awardees will be expected to develop and implement common, uniform standard operating procedures (SOP) 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.

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 will have a 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 awardee 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 awardees as appropriate
• Facilitating coordination of project activities during the course of the project
• Assisting the awardee with access to other NIDCR-supported resources and services
• Monitoring progress of the RCs as a whole and of the specific ITP projects 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 awardees and the programmatic team
• Negotiating project specific timelines and milestones with grantees during the funding phase
• Conducting periodic site visits or discussions with awardee 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 awardees to the approved resource and data sharing plans
• Monitoring rigor and reproducibility of the conducted research

Additionally, NIDCR Program Official 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 awardees and NIH staff as described above.

Additional notes:

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

The RCs Steering Committees will direct the overall efforts of the RCs and the ITPs. The steering committees will be composed at a minimum of PDs/PIs of each of the RCs and a NIH Project Scientist serving as the representative of the NIH. The RCs Steering Committees will make recommendations related to all aspects of the RCs development and function, and will monitor the progress of funded projects. Periodic interactions between the RCs' steering committees will be implemented.

Dispute Resolution:

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

3. Reporting

These awards will require semi-annual Progress Reports

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.

Section VII. Agency Contacts

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Nadya Lumelsky, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-7703
Email:nadyal@nidcr.nih.gov

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email:yasaman.shirazi@nih.gov

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email:rutbergd@mail.nih.gov

Section VIII. Other Information