National Institute of Dental and Craniofacial Research (NIDCR)
New
August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
RFA-DE-20-006, R01 Research Project Grant
93.121
The purpose of this Funding Opportunity Announcement (FOA) is to encourage high risk high reward studies that will interrogate the capacity of cells residing in the postnatal Dental, Oral, and Craniofacial tissues to acquire developmental plasticity to undergo lineage reprogramming in vivo in response to injury and other types of environmental stress, and to generate functionally-competent cells of alternative lineage(s). The end goal of this initiative is to develop approaches that willexplore new opportunitiesfor capitalizing on this developmental plasticity for obtaining needed cells to promote endogenous regeneration of DOC tissues affected by disease or injury and to achieve the goals of regenerative medicine. This Initiative will aid in building a basic science foundation for developing clinically relevant, minimally invasive strategies for overcoming limitations of the currently available regenerative medicine methodologies.
March 13, 2020
30 days before the application due date
July 8, 2020; No late applications will be accepted for this Funding Opportunity Announcement
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
October 2020
January 2021
April 2021
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.
Research Objectives
Regenerative medicine strives to heal and functionally and structurally restore tissues and organs compromised by disease or injury. Advances are continually being made in this area; however, one of significant remaining bottlenecks impeding progress has been an inadequate supply of cells for generation of new tissues. Currently available methods often rely on injection into tissues of in vitro expanded heterogeneous stem and progenitor cell populations or in vitro differentiated progeny of pluripotent cell lines. While there have been promising developments in these areas, many challenges remain, including insufficient characterization of stem/progenitor cells as to their capacity to generate functional progeny, low numbers of cells available for building new tissues as well as poor function, survival and integration of the injected cells with host tissues. The present initiative addresses these obstacles, through promoting endogenous healing and regeneration of Dental, Oral, and Craniofacial tissues, which will avoid injection of exogenously manipulated cells. The immediate purpose of this Funding Opportunity Announcement (FOA) is to build a basic science foundation for understanding mechanisms of endogenous lineage reprogramming of Dental, Oral, and Craniofacial tissues. To this end, this FOA will support studies that interrogate the capacity of cells residing in the postnatal Dental, Oral, and Craniofacial tissues to acquire developmental plasticity to undergo lineage reprogramming in vivo in response to injury and other types of environmental stress, and to generate functionally-competent cells of alternative lineage(s) that can be induced to participate in endogenous tissue regeneration. The long-term goal will be to develop practical approaches for capitalizing on this developmental plasticity for obtaining needed cells for building new Dental, Oral, and Craniofacial tissues and derive clinically relevant minimally invasive strategies for overcoming limitations of currently available regenerative medicine methodologies.
Background
The capacity of DOC tissues to undergo endogenous healing and regeneration remains largely unexplored. It varies widely among species, types of Dental, Oral, and Craniofacial tissues, and the extent of incurred injury. For example, following cuts and abrasions, normal human oral mucosa heals better and faster than most other tissues in the body. On the other hand, oral cancer chemotherapy and radiation commonly result in nonhealing lesions of oral mucosa - oral mucositis - a condition responsible for severe patient morbidity. Human dental and salivary gland tissues do not exhibit significant regenerative capacity, while rodent incisors regenerate throughout life. Human craniofacial bone and skeletal muscle regenerate small defects but fail to do so when the defect exceeds critical size and/or in the presence of infection and chronic inflammation. While mechanisms of differential regenerative capacity of tissues are complex and still poorly understood, it is recognized that the availability of stem/progenitor cells to generate new tissues is one of the key factors needed for successful regeneration. Traditionally, in mammals the developmental progression from stem/progenitor cells to fully differentiated functional cells has been viewed as a unidirectional and terminal process, but recent advances beginning with a derivation of induced pluripotent stem cells and a discovery of cellular reprogramming, put the universality of this simple paradigm into question. In fact, multiple examples of naturally occurring in vivo reprogramming of differentiated cells into stem/progenitor state following injury and/or inflammatory stress have been described. The best-studied example of this phenomenon is found in mammalian small intestine, but similar findings have been described in lung, skin, pancreas, liver, brain and heart, tooth and bone. Alternatively, and/or in addition, lineage reprogramming in vivo can be induced by targeted gene transfer to deliver to cells genes coding for master tissue-specific genetic and epigenetic regulators via viral vectors or other gene transfer technologies. Accomplishing controlled and safe in vivo lineage reprogramming would provide minimally invasive means for generating needed cell sources. Moreover, such reprogrammed cells are likely to have multiple advantages over injected in vitro-manipulated cells, because survival, function and integration of in vivo reprogrammed cells with host tissues would be supported by endogenous Dental, Oral, and Craniofacial stem cells niches. In these niches, accessory somatic cells, soluble signaling mediators and extracellular matrices would provide guidance cues to stem/progenitor cells to generate new tissues. Overall, achieving the goals of this initiative will create unprecedented opportunities for healing and regeneration of Dental, Oral, and Craniofacial tissues.
Gaps and Opportunities
Significant knowledge gaps currently exist in understanding of the mechanisms of inherent and induced lineage plasticity of mammalian Dental, Oral, and Craniofacial tissues and the role of stem cells niches and other signals, including immune system-mediated signals, in controlling this plasticity. Overcoming these knowledge gaps is likely to create a new generation of approaches - autotherapies - that take advantage of endogenous healing and regeneration capacity of Dental, Oral, and Craniofacial tissues to restore their structure and function. More specifically, these autotherapies will target endogenous Dental, Oral, and Craniofacial stem/progenitor cell niches and differentiated somatic cells for lineage reprogramming for generating new cells for re-building Dental, Oral, and Craniofacial tissues and restoring normal tissue homeostasis. Currently, NIDCR portfolio does not contain projects directly focusing on in vivo lineage reprogramming. However, recent findings in the field have provided promising results suggestive of inherent lineage plasticity of Dental, Oral, and Craniofacial tissues. Further, recent emergence of new experimental tools and approaches for interrogation lineage plasticity suggests the timeliness of this effort. Several NIH Institutes including NIDDK, NIAMS, NHLBI and NINDS, currently support such projects as applied to those Institutes' missions. The proposed NIDCR initiative is synergistic with this existing trans-NIH effort. Moreover, a Keystone Symposium titled "Cellular Plasticity: Reprogramming, Regeneration and Metaplasia", was held in January 2019 and another Keystone Symposium titled "Tissue Plasticity: Preservation and Alteration of Cellular Identity" is being planned for October 2020. These conferences are indicative of a robust interest of the scientific community, and of a critical mass of knowledge being generated in this new field. Given the strong interest of NIDCR in advancing Dental, Oral, and Craniofacial tissue regeneration, it is important for the Institute to join this effort. To achieve maximum results, this initiative will highly encourage collaborations of Dental, Oral, and Craniofacial tissue regeneration experts with investigators exploring lineage plasticity and reprogramming of other tissues in the body.
Scope and Areas of Interest
The long-term goal of this FOA within an umbrella of NIDCR 2030 Theme Autotherapies, is to develop practical approaches for capitalizing on developmental plasticity of Dental, Oral, and Craniofacial tissues for their healing and regeneration. To achieve these goals, it will be necessary to build a strong basic science knowledge base to define the capacity of Dental, Oral, and Craniofacial cells to undergo in vivo lineage reprogramming in response to injury and other types of environmental stress, elucidate molecular and cellular mechanisms, identify signaling pathways and mediators of this reprogramming, and develop approaches for optimizing safety and efficiency of reprogramming in appropriate animal models. While this FOA is focused on lineage reprogramming in vivo, employment of in vitro model systems, would be within the scope of this FOA, as long as the proposed experimental plans address questions relevant to reprogramming in vivo. Employment of tools and technologies such as, single cell-based analyses, including single cell transcriptomics, epigenomics and proteomics; bioinformatics, machine learning or systems biology; tissue organoids or tissue/organ on chips; bioengineering, genome-editing or gene transfer; high-resolution real-time imaging, among others are expected. The specific areas of interest include but are not limited to those listed below:
- Elucidation of the molecular and cellular mechanisms and the nature of signaling mediators and pathways of Dental, Oral, and Craniofacial cell lineage reprogramming
- Investigation of the innate and adaptive immune system- mediated mechanisms of Dental, Oral, and Craniofacial cell lineage reprogramming
- Investigation of molecular and cellular components and modes of interactions within Dental, Oral, and Craniofacial stem cell niches that mediate lineage reprogramming
- Elucidation of developmental relationships and dynamic lineage transitions among cells comprising Dental, Oral, and Craniofacial stem cell niches that underlie tissue regeneration in response to injury or environmental stress
- Derivation of new and refining existing approaches, including bioengineering approaches, for targeted manipulation of in vivo tissue microenvironment to achieve efficient and safe Dental, Oral, and Craniofacial cell reprogramming
- Derivation of new and refining existing animal models, including mouse genetic models to serve as experimental systems for studies of Dental, Oral, and Craniofacial cell lineage reprogramming
- Derivation of in vitro systems to serve as experimental systems for studies of Dental, Oral, and Craniofacial tissue lineage reprogramming
- Development of cell type-specific biomarkers of Dental, Oral, and Craniofacial cell lineage reprogramming
- Development and refining strategies for targeted gene manipulations of defined cell populations to allow interrogation of Dental, Oral, and Craniofacial cell plasticity
- Derivation of functional assays and readouts for monitoring Dental, Oral, and Craniofacial cell lineage reprogramming
The following areas of focus for research projects are not responsive to this FOA:
- Projects employing single cell analysis, such as transcriptomics, epigenomics and proteomics, but not directly related to investigation of Dental, Oral, and Craniofacial cell lineage plasticity
- Projects that focus on developing and/or utilizing tools and technologies listed in Specific Areas of Interest above, but not directly related to investigation of Dental, Oral, and Craniofacial cell lineage plasticity
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Need help determining whether you are doing a clinical trial?
NIDCR intends to commit $3M total costs in FY 2021 to fund 5-8 awards solicited from RFA-DE-20-007 and its companion,RFA-DE-20-006.
The scope of the proposed project should determine the project period. The maximum project period is 2 years.
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)
- Eligible Agencies of the Federal Government
- 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
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
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)
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
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guideexcept where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Names of other key personnel
- Participating institution(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
Dr. Yasaman Shirazi
Telephone: 301-594-5593
Email: [email protected]
This FOA encourages collaborations a?m?o?n?g investigators already involved in studies of endogenous lineage plasticity and reprogramming of Dental, Oral, and Craniofacial and other types of tissues with those who are only entering this field. It requires that expertise and prior experience in studying lineage plasticity and reprogramming be present on the team. For those investigators who are only entering the field, multi-PI applications are highly encouraged. Additionally, if one or more types of single-cell analyses are involved in the project, bioinformatics expertise on the team is required.
All instructions in the SF424 (R&R) Application Guide must be followed.
The Research Plan is required to address the following topics:
- How the scope of the proposed project directly addresses endogenous lineage reprogramming of Dental, Oral and Craniofacial cells
- ?How the scope of the proposed project fits the exploratory high risk high reward nature of R21 mechanism
- How the proposed Specific Aims will allow achieving the goals of the proposed project
- What existing or to be developed in vivo or/and in vitro model systems, including injury model system, will be employed
- Which functional assays and readouts will be used to detect lineage reprogramming events
- Which strategies will be used for detecting, monitoring and tracing lineage reprogramming events in the heterogeneous cell populations of Dental, Oral and Craniofacial tissues and organs
- Which cell type specific biomarkers will be used for detecting lineage transitions
- Which approaches will be employed for analyzing lineage plasticity of Dental, Oral and Craniofacial cells on a single-cell level
- How endogenous Dental, Oral and Craniofacial tissue regeneration will be tested and monitored
The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, are required to address a Data 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.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
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 for responsiveness by NIDCR, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
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.
The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
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?
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?
Is the expertise on the project is appropriate for the work proposed?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the 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?
- Are proposed in vivo and/or in vitro models appropriate for achieving the goals of Specific Aims?
- Are functional assays and readouts appropriate to monitor Dental, Oral, and Craniofacial lineage reprogramming and tissue regeneration?
- Are appropriate biomarkers to be used for detecting lineage transitions defined?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not applicable
Not applicable
Not applicable
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) 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.
- May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- Will receive a written critique.
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.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.
Institutional Review Board or Independent Ethics Committee Approval: Grantee 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor 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.
3. Reporting
When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.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 agreementsare 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.
Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:[email protected](preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:[email protected]
Nadya Lumelsky, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-7703
Email:[email protected]
Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: [email protected]
Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email:[email protected]
and Human Services (HHS)
