Part 1. Overview Information

Key Dates

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

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

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

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) will support, through the cooperative agreement mechanism, investigator-initiated observational studies or biomarker validation studies that require prospective collection of data/biospecimens or continued analysis of data/biospecimens collected as part of a previous NIDCR cooperative agreement.

Background and Scope

NIDCR is committed to identifying effective preventive, diagnostic and treatment approaches for dental, oral and craniofacial diseases and disorders. Improving health through the generation of high-quality data from adequately-powered, well-executed clinical studies is a high priority for NIDCR.

Various types of well-designed clinical studies involving the prospective collection of data and/or biospecimens have the potential to generate robust data and contribute to the knowledge base to improve oral health. Longitudinal studies allow for prospective assessment of risk factors (exposures) and their relation to disease development. Also, disease and standard-of-care treatment outcomes can be observed and measured systematically. A biomarker analytic and/or clinical validation study is designed to validate a strong candidate biomarker measure(s) or endpoint(s) for which robust preliminary data exist that support utility in diagnosis, prognosis, monitoring, and/or prediction of response to treatment. Rigorous scientific inquiry in genetics, gene expression, gene regulatory pathways, gene-environment interactions, metabolism, or disease/treatment mechanisms through -omics analyses require large numbers of study participants from whom biospecimens are collected in a standardized manner. Biospecimen analyses can include epi/genomic, epi/transcriptomic, protein, cellular, metabolomic, imaging, and physiologic endpoints. Continued analysis of potential targets in preclinical models may contribute to knowledge gaps in the pathophysiology of disease and/or pathways for treatment.

Because prospective observational and biomarker analytic and clinical validation studies are resource intensive, NIDCR anticipates funding only those studies of highest priority and mission relevance. Aspects of studies that are of key interest to NIDCR include the appropriateness of the design to answer the study question, rigor in exposure and outcome assessment, evidence that an appropriate study population can be enrolled quickly and be retained, selection of appropriate methodologies for biospecimen collection, storage and analysis, and involvement of collaborators with expertise in the design, implementation and analysis of large observational studies, such as experienced statisticians and data managers. For applications proposing prospective collection of data and/or biospecimens, we strongly encourage that the investigative team include a data coordinating center. Investigators considering preparing and applying are strongly encouraged to consult with NIDCR Scientific/Research staff prior to beginning the application process to determine NIDCR interest in the concept that would be proposed in the application.

Prospective observational studies: Study designs considered appropriate to this NOFO would be epidemiologic studies of disease prevalence or incidence, cohort studies prospectively ascertaining risk factors for disease development, cohort studies that provide longitudinal follow-up of treatment outcomes, case-control studies with longitudinal follow-up, and large cross-sectional studies or case-control studies evaluating genomic changes, gene-environment interactions, or disease/treatment mechanisms through -omics, cellular, and imaging analyses. Research studies may be proposed for long-term follow-up of clinical trial participants after a preventive or therapeutic intervention, and the initial trial has ended. The additional follow-up could be used to assess long-term adverse events, sustained effects of the intervention, or to collect additional data that could potentially create combined cohorts to uncover new knowledge.

Biomarker validation studies: This NOFO will promote advanced analytic and/or clinical validation of strong candidate biomarkers and endpoints for diagnostic or prognostic utility to demonstrate that biomarker or endpoint change is reliably correlated with pathophysiology, clinical outcome, therapeutic target engagement or treatment response. It is assumed that a candidate biomarker has been identified and assay technology or method of detection has been developed. Specifically, it is expected that the initial discovery of the biomarker or assay will have been performed on a pre-existing set of human biospecimens with the same disease or condition as that in the proposed validation application. This biomarker validation NOFO will support analytic validation studies that establish the accuracy, precision, sensitivity, specificity, reportable range of test results for the test system, reference intervals (normal values) with controls and calibrators; establish the desired magnitude and reliability of the association between the biomarker or endpoint and disease pathophysiology, clinical outcome, target engagement or treatment response; and demonstrate test reproducibility and harmonization of assays or equipment across testing sites. This NOFO will also support clinical validation studies that validate the proposed biomarkers in a new, independent cohort to estimate the prevalence of the marker within patients for the intended clinical use; establish that the biomarker or endpoint acceptably identifies, measures, or predicts response for the disease or condition of interest; and establish an appropriate cut-off or threshold for a biomarker assay for the intended clinical context.

This NOFO will not support the biomarker and endpoint Discovery Phase, which may include initial identification, development of detection technology, and preliminary validation studies, such as initial analytic validation of the detection method along with studies designed to correlate modulation of the biomarker or endpoint with disease pathology, target engagement, or treatment response. These applications will be considered non-responsive and will not proceed to review.

Examples of studies that might be supported by this NOFO include, but are not limited to:

• Applications of multi-center observational cohort studies assessing preventive and risk factors for development or progression of dental, oral or craniofacial diseases (e.g., dental caries, periodontal disease, head and neck cancer, orofacial pain conditions, oral sequelae of systemic conditions);
• Applications of observational cohort studies assessing treatment outcomes for oral diseases or conditions (e.g., periodontal disease, Sjögren's syndrome, craniofacial anomalies, orofacial pain conditions);
• Research to study oral health outcomes in medically complex patients, such as those with oral sequelae of systemic treatments or conditions;
• Research to establish the natural history of oral infections and their persistence (e.g., oral HPV infection);
• Research to study the effectiveness of standard of care periodontal therapy for those with type 1 or type 2 diabetes and factors that predict response to therapy;
• Observational cohort or cross-sectional studies developing or establishing algorithms for tailoring or targeting behavioral or social interventions for individuals, groups, communities, or settings in which further assessment is justified;
• Development of predictive tools for optimizing disease prevention and treatment.
• Applications that leverage existing biospecimens, data and/or epidemiologic cohorts to further promote high quality data sharing, consistent with the NIH Data Management and Sharing (DMS) Policy, and generation of additional multidimensional using new analytic methods and technologies.
• Applications of cross-sectional or cohort studies collecting and analyzing biospecimens through -omics to assess risk for or treatment responses to dental, oral, and/or craniofacial diseases including craniosynostosis and orofacial clefting;
• Applications of cross-sectional or cohort studies collecting and analyzing biospecimens to assess mechanisms of dental, oral, and/or craniofacial diseases or treatment pathways through analyses of -omics data such as genomics, epigenomics, transcriptomics, epitranscriptomics, proteomics, metabolomics, or metagenomics;
• Applications of cohort studies assessing associations of psychosocial and behavioral factors with -omics changes (including epigenetic modifications to the human genome and/or oral microbiome alterations) and impact of the associations upon oral diseases and conditions;
• Applications of cohort studies that analyze interaction of the human genome and oral microbiome in response to environmental stimuli and impact of the interaction on oral diseases and conditions;
• Applications proposing analysis of complex codependencies that include oncogene addiction, tumor-suppressor hypersensitivity and metabolic dependencies in oral cancer and the identification of combinations of targets which could be exploited for therapeutic interventions;
• Applications of analytic validation using biospecimens appropriate for the clinical context of the intended use to establish analytic metrics and harmonization of assays for the biomarker(s) of interest;
• Applications of clinical validation of biomarker(s) through prospective collection, with the goal of establishing robust correlations between biomarker and dental, oral or craniofacial disease detection or therapeutic response.

Applicants should also consider the relevance of their proposed research to NIDCR programs and priorities as described in the NIDCR Strategic Plan.

This NOFO will not support studies that meet the NIH Definition of a Clinical Trial. Investigators proposing clinical trials must use NIDCR NOFOs soliciting applications for clinical trials.

The proposed clinical study must meet all applicable NIH and Office of Human Research Protections (OHRP) policy requirements. Awardees are required to comply with NIDCR Clinical Terms of Award. After NIDCR approval of the final clinical research protocol and associated documents, clinical sites will complete study staff training and other site initiation activities prior to study subject recruitment. The materials contained in the U01 application should be sufficient to demonstrate readiness to complete site initiation requirements in a timely manner, once the study documents are approved.

Investigators considering smaller prospective observational studies should consider submitting a NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) application or an application in response to other appropriate NOFOs. Investigators are strongly encouraged to consult with NIDCR Scientific/Research staff prior to beginning the application process regarding the suitability of this NOFO for their particular study.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• 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)

Local Governments

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

Federal Governments

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

Other

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. 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.

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:

Yasaman Shirazi, PhD
Telephone: 301-594-5593
Email: [email protected]

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: The information provided here will be considered by reviewers and is meant to supplement, not duplicate, information provided in the Research Plan or the Study Record: PHS Human Subjects and Clinical Trials Information form. The application must contain a Quality Management Plan and Clinical Data Management Plan, according to the instructions below.

1. Quality Management Plan. The purpose of the Quality Management Plan is to establish standard processes for all study-related activities, to assess and document adherence to all clinical study procedures, and to ensure the quality of data collection procedures.

• Describe plans to standardize study processes, train study staff, and monitor adherence to the clinical protocol.
• Describe the methods and systems for data collection (e.g., Case Report Forms/CRFs), including timely data entry, and review to ensure accurate and consistent data collection.

2. Clinical Data Management Plan. The purpose of the Clinical Data Management Plan is to establish validated systems and controls to ensure the integrity of the clinical research data being collected for the proposed study.

• Describe the methods and systems for data verification and data validation. Describe the frequency of data verification, data query process, and any planned mitigation strategies in the event of data system noncompliance.
• Describe methods and systems to ensure data confidentiality and subject privacy.

If the proposed study involves prospective data collection, the application must also contain a Schedule of Events, according to the instructions below.

3. Schedule of Events.

• Provide a schematic, table, or text description of the protocol-specified schedule of events for an individual study participant. It should capture each study visit/assessment time point and planned activity(ies) for each time point.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

A detailed budget with budget justifications must be included for the entire study and data analysis period.

If parts of the costs of the study are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

Significance:

The significance and biological relevance of the proposed study must be stated clearly. It should be supported by the following:

• Provide a clear statement of the question(s) that the study will address and its importance.
• Describe the scientific rationale and clinical need (if applicable) for the study, including an assessment of previous preclinical and/or clinical studies and their quality.
• Describe the potential for the study results to impact knowledge, clinical practice or health care policy
• For biomarker validation studies, provide supporting data to demonstrate that the candidate biomarker identifies, measures or predicts the disease or condition of interest.
• For biomarker validation studies, describe the current status of initial analytic validation and preliminary analytic performance of the biomarker(s) in human specimens within the intended clinical context.

Approach:

• Address the feasibility of recruiting participants who are eligible for the proposed research. For an application proposing a multi-site study, applicants are expected to provide evidence that each recruiting center has access to sufficient study participants who meet the eligibility criteria.
• Provide a concise snapshot of the planned clinical study. It is expected to:
  • Clearly state the study objectives.
  • Describe and provide rationale for the study design, including study groups and number of sites.
  • Specify the primary and important secondary outcome measures that align with each objective, provide justification for their selection, and describe how they will be collected and the criteria for measuring them.
  • Describe the study population, including the sample size, pertinent demographic information, required health status or disease condition, and geographic location. Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information.
  • Provide a statistical analysis plan, including power calculations, data analysis approaches, and plans for handling missing data.
• Discuss potential biases or challenges in the proposed study and how they will be minimized and/or addressed.
• For biomarker analytic validation studies, describe the plans to evaluate performance of the biomarker assay(s) (e.g. accuracy, precision, sensitivity, specificity, reportable range of test results, reference intervals (normal values) with controls and calibrators, reproducibility, and magnitude and reliability of the association between biomarker and outcome).
• For biomarker clinical validation studies, describe the number of study participants/biospecimens needed to test prevalence of the marker and associate assay results with a pre-specified clinical outcome within the intended clinical context of use and establish the threshold or cut-off for the assay.
• For studies involving genomic or -omics analyses, provide the plan for biospecimen analysis.

Letters of Support: Letters of support from clinical partners, research collaborators, or other groups the investigators propose to work with should be included.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Other Plan(s): 

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• The Data Management and Sharing Plan attachment is in addition to, and separate from, the Clinical Data Management Plan attachment. 

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

If applicable, describe plans and strategies for participant recruitment/enrollment, including outreach activities and pre-study assessments of the ability of participating sites to recruit the proposed target number of participants. Describe approaches to be used for retention and follow-up of enrolled participants and address any anticipated changes in the composition of the study population over the course of the study.

2.7 Study Timeline

Provide a timeline for implementing and completing the study, including the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis.

Section 3 - Protection and Monitoring Plans

3.5 Overall Structure of the Study Team

For studies that include multiple sites and/or a separate data coordinating center or laboratory, describe the organizational structure and communication plans for the study.

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 8 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the How to Apply-Application Guide.

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

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIDCR, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

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

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

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

Successful recipients under this NOFO agree that:

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

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

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

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

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

• Providing scientific leadership for all aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The PD(s)/PI(s) agrees to accept close coordination, cooperation, and participation of NIDCR staff in those aspects of scientific and technical management of the study as stated in these terms and conditions;
• Adhering to the NIDCR Clinical Terms of Award  requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study;
• Upon implementation of the study, following the procedures required by the protocol regarding study conduct and monitoring, participant management, data collection, and quality control;
• Retaining custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies;
• Managing involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NIDCR;
• Managing procedures to comply with the requirements of 45 CFR Part 46 for the protection of human subjects and the NIH policy requirements for the inclusion of women, minorities, and children;
• Making all study materials, procedure manuals, and final datasets available in the public domain. Recipients are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIH/NIDCR;
• Obtaining prior written approval of the NIDCR Grants Management Specialist, in consultation with the NIDCR Program Officer, for changes in any of the key personnel identified in the Notice of Grant Award.

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

An NIDCR Project Scientist will be assigned. The NIDCR Project Scientist will:

• Serve as a resource to provide scientific/programmatic support during implementation of the research by providing input on experimental and clinical approaches and study protocols, and advising in the management and operational aspects of the research;
• Participate on teleconferences with PD(s)/PI(s) to monitor study progress, adherence to the study protocol, conduct of the study, and accrual and retention of study participants;
• Review the progress of the study, and of each participating component, through consideration of routine reporting, site visits, oversight committee recommendations, etc. This review may include, but not be limited to, compliance with the study protocol, meeting participant enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

An NIDCR Program Official will be assigned. The NIDCR Program Official will:

• Carry out continuous review of all activities to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines;
• Have the option to withhold support to a participating institution if technical performance requirements are not met;
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the notice of award.”

An NIDCR Medical Officer will monitor the studies and serve as the Medical Monitor.

• The NIDCR reserves the right to terminate or curtail a study or any portion of a study in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which the NIDCR does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

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

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel comprising three members will be convened. Members will be: a designee chosen by the PD/PI, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (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: 301-480-7075

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

Lorena Baccaglini, DDS, MS, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-435-7908
Email: [email protected]

Dena Fischer, DDS, MSD, MS
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4876
Email: [email protected]

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: [email protected].

Gabriel Hidalgo
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: 301-827-4630
E-mail: [email protected]

Section VIII. Other Information

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

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