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

The purpose of this NOFO is to provide support for the planning and implementation of meticulously designed, rigorously conducted, behavioral and biopsychosocial intervention studies relevant to dental, oral, and craniofacial (DOC) health as well as associated medical and mental health status or comorbidities.  This NOFO will not support the testing of drugs, devices, or biologics regulated by the FDA; the corresponding NOFO for such clinical trials is PAR-25-057.

A broad range of intervention research projects that meet the NIH definition of a clinical trial are of interest.  Such projects include, but are not limited to:

• Participants of any age or developmental stage;
• Participants with developmental disabilities such as autism, cerebral palsy, Down syndrome, or others create challenges in accomplishing daily activities, especially self-care;
• Biopsychosocial, behavioral, and structural variables as outcomes and/or causal change mechanisms;
• DOC targets with health significance, including, and not limited to, care delivery to those with birth defects, craniofacial abnormalities, dental caries, interprofessional care, oral hygiene promotion, oral manifestations of autoimmune/rheumatologic conditions, oral speech pathologies and rehabilitation, pain management, periodontal diseases, salivary disorders, social and behavioral genomics, Sjögren’s syndrome, and temporomandibular joint and muscle disorders (TMDs);
• Relevant medical/mental health comorbidity or health/behavior status, including conditions that can influence DOC health including arthritis, cancer, cardiovascular disease, dementias, diabetes mellitus, inflammation, kidney disease, obesity, and xerostomia (dry mouth)—though this list is not exhaustive;
• A range of outcomes (e.g., direct intervention with patients to improve outcomes; intervention with practitioners to improve care; intervention on health systems to improve precision, provision, or continuity of care; direct intervention with non-clinical populations to promote healthier behavior as well as adherence to health maintenance protocols, etc.);
• Stakeholders from different sectors (e.g., patients, families, social networks and communities, practitioners, care-delivery systems, professional organizations, local governments, civic organizations, human services organizations, policymakers, etc.);
• Traditional methods as well as novel/advanced features for intervention design and/or delivery, data retrieval, mobile health applications, telehealth, responsive health system records, sophisticated methodologies, e.g., Sequential Multiple Assignment Randomized Trials (SMART) or other sequential randomization designs, etc.  For additional information, the NIH Office of Disease Prevention provides resources on study design, intervention design, data analysis, and measurement methods. 
• Prevention of DOC conditions or diseases among women for which they are expressly susceptible. Equally encouraged are projects designed to improve treatment outcomes for DOC diseases and conditions in which women experience disparate treatment outcomes. For additional information, see the NIH Office of Research on Women’s Health Opportunity Map;
• Identifying and mitigating prenatal environmental and physical stressors experienced during pregnancy that affect children’s dental, oral, and craniofacial tissues through altered maternal physiology;

Background

The NIDCR Behavioral and Social Sciences Research Branch (BSSRB) supports basic, intervention, and translation research to promote DOC health, prevent DOC diseases and related disabilities, and improve management of craniofacial conditions, disorders, and injury.  DOC conditions can trigger, moderate, mediate, co-exist, or arise out of other health conditions or well-being processes.  The Branch views DOC health as one component of a larger system of medical and person health, and the Branch encourages perspectives that incorporate multiple aspects of health and well-being.

UG3/UH3 Cooperative Agreement - Overall

This NOFO uses a UG3/UH3, biphasic, Cooperative Agreement.  The UG3/UH3 application must be submitted as a single application.  Clarity and organization in the application should be meticulous in order to support understanding each of the two phases, how information from the UG3 phase is planned to inform the UH3 phase, and an operational framework to account for uncertainties that could arise from proposing, in one application, both phases.

Overall goals and hypotheses of the entire project are required in the application.  This should include a discussion of a hypothesized mechanism of causal change (or provide a compelling argument within the application as to why at least one causal hypothesis is not applicable).  Additionally, specific aims and research plans for each of the UG3 and UH3 phases are required.

Study Timeline and Milestone Plan

A Study Timeline and Milestone Plan must be included in the application to cover both the UG3 and UH3 time-periods.  The Study Timeline and Milestone Plan must include a schedule of events during the UH3 phase as well as clearly stated annual UG3 and UH3 milestones that will be completed.  Applications submitted without a Study Timeline and Milestone Plan will be considered incomplete and will not be reviewed.

A milestone is defined as completion of an important stage, event, or task in the project that signifies progress towards, or accomplishment of, a major project activity.  Annual milestones must be objective, measurable, achievable, and serve as scientific and/or operational accomplishments.  .  In the event of an award, milestones will be refined and finalized in consultation with NIDCR staff  for each year of the UG3 and UH3 phases.  If at any time the project fails to meet annual milestones, NIDCR will consider ending support and negotiating an orderly close-out of the project.

Clinical Trial Planning Phase (UG3)

The UG3 award may provide one year of support for scientific, development, and operational planning activities necessary to conduct the subsequent UH3 clinical trial.  Specific aims and a research plan are required for the UG3 phase, and they may include the following, if appropriate:

• Development or finalization of tools, methods, applications, algorithms, techniques, etc.  Establishment of the reliability and/or validity of (new) measures.  Acceptability, feasibility, or testing of aspects of the study intervention(s) or procedures.  Development and finalization of the upcoming UH3 clinical protocol and other required documentation.  Required documentation can include a clinical protocol, manual of procedures, clinical quality management plan, data quality management plan, etc. as appropriate.  Templates for such documentation can be seen on the NIDCR website.  Note: A full pilot of the UH3 planned intervention is prohibited in the UG3 planning phase.
• Sample size estimations, effect size analysis, or power analysis.
• Development of fidelity monitoring procedures.  
• Completion of the data management system.
• Finalization of all materials required for regulatory approvals (IRB and applicable oversight committees).
• Finalization of agreements for use of resources available within NIH-funded Clinical and Translational Science Awardees (CTSAs), practice-based research networks, patient, registries, etc., as applicable.
• Finalization of any other documents necessary to implement the trial.

Transition to the UH3 Phase:

An administrative review will determine whether the UH3 phase award will be issued, subject to funding availability.  Applicants and recipients of UG3 funding should note that the UG3 award does not guarantee subsequent UH3 funding.  With NIDCR approval, information generated during the UG3 phase might be used to revise UH3 activities, milestones, or timeline.  

Clinical Trial Implementation Phase (UH3)

The UH3 award may provide up to 5 years of support to conduct the clinical trial in accordance with activities planned in the UG3 phase.  NIDCR requires clinical trials supported during the UH3 phase to include annual milestones, and the length of the UH3 phase should be commensurate with the work proposed.  Specific aims and a research plan are required for the UH3 phase, and they must include the following operational achievements, expressed as UH3 annual milestones:

• Completion of regulatory approvals (e.g., IRB), documents, and site activation activities.
• Registration of clinical trial in ClinicalTrials.gov.
• Enrollment of the first subject.
• Fulfillment of Study Accrual and Retention (SARP) targets.
• Completion of data collection.
• Completion of primary study analyses.
• Completion of the final study report.
• Additional milestones, as appropriate.

Pre-Application Consultation:

Applicants are strongly encouraged to consult with NIDCR staff about their proposed project early in the planning of an application.  This early contact will provide an opportunity to discuss and clarify NIH and NIDCR policies and guidelines, including the scope of the project and intent of this NOFO.  See the Scientific Program Contact information in Section VII of this NOFO.

Applications Not Responsive to this NOFO:

Applications that meet any of the following will be considered non-responsive and will not be reviewed:

• Applications that do not include overall goals and hypotheses of the entire project as well as specific aims for each of the UG3 and UH3 phases.
• Applications that do not include a Study Timeline and Milestones Plan, which includes a timeline for the UH3 phase as well as annual milestones for the UG3 and UH3 phases.
• Applications that do not include at least one NIH-defined clinical trial in the UH3 phase.
• Applications that do not discuss a hypothesized mechanism of causal change (or provide a strong argument within the application as to why at least one causal hypothesis is not applicable for the proposed research).
• Applications that include the testing of drugs, devices, or biologics regulated by the FDA. 

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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).

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, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research ( NIDCR )
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.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

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:

The UG3/UH3 application must be submitted as a single application.  Clarity and organization in the application should be meticulous to facilitate understanding each of the two phases and how information from the UG3 phase will inform the UH3 phase. In addition, an operational framework should account for any uncertainties that could arise from proposing both phases in a single application.

Investigators should consider that the application will be assigned a single overall impact score.  Thus, interrelated completeness of the application is critical.  It is not necessary to repeat information or details in the UH3 section that are already sufficiently described in the UG3 section.

Overall goals and hypotheses of the entire project are required.  Describe the rigor of prior research and indicate how scientific knowledge will be improved if the aims are achieved.  This should include a discussion of the significance of the project, a hypothesized mechanism of causal change (or a compelling argument as to why that is not applicable), and a brief overview of the approach that will be adopted.  Additionally, specific aims for each of the UG3 and UH3 phases must be stated.  Describe how successful completion of the aims may change or add to the accumulated science.

Research Strategy:

The research strategy should contain separate sections detailing the activities pursued in each of the UG3 and UH3 phases, appropriate to their respective specific aims.  The UG3 section will tend to focus on development, planning, building, establishing feasibility of methods or procedures, testing aspects of interventions, linking data sets, establishing psychometric properties of new measures, determining subject flow and characteristics, sample sizes, power analysis, etc.

The UH3 section should focus on articulation of the clinical trial – subjects and their recruitment, ns, design, methods, assessment, measures, approach, procedures, statistical plan, etc. as appropriate.  Particular attention should be paid to the detail of the intervention(s), fidelity monitoring, and assignment of subjects to the intervention(s).  The UH3 section should provide information sufficient to understand issues around subject consent, safety, and confidentiality.

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

Other Plan(s): 

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

• 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. 

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.

Additional instructions are provided for the following sections:

• 2.5 Recruitment and Retention Plan
• 2.7 Study Timeline
• 3.3 Data and Safety Monitoring Plan
• 4.3 Statistical Design and Power

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

The filename "Study Accrual and Retention Plan" should be used to name this attachment, which addresses the feasibility of recruiting participants who are eligible for the clinical trial.  Specifically, applicants must provide evidence that each recruiting center in the trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the grant application.  For multi-site applications, information must be provided for each participating site.

Describe the plan to recruit/enroll the population of interest for the clinical trial, including outreach activities and pre-study assessments of the ability of participating clinical sites to recruit and enroll the proposed target number of participants.  The plan should include a timeline with goals for accrual of study participants.  If there are known participant- or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success.  Address contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks.

Describe the plan to meet the study’s retention targets.  Include a discussion of strategies for retention of participants, including any methods to maximize flexibility for data collection after baseline (e.g., data collection independent of office visits).  The plan should clearly state retention goals.

2.7 Study Timeline

The filename "Study Timeline and Milestone Plan" should be used to name this attachment, which should include both the Study Timeline and Milestone Plan.

1. Study Timeline

The UH3 timeline should include the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis.  Provide a clear and appropriate timeline to ensure the study will be completed during the project period.

Applications that lack the Study Timeline are considered incomplete and will be withdrawn without peer review.

2. Milestone Plan

A milestone is defined as completion of an important stage, event, or task in the project that signifies progress towards, or accomplishment of, a major project activity.   Milestones must be objective, measurable, achievable, and serve as scientific and/or operational accomplishments.  This document must include clearly stated annual UG3 and UH3 milestones that will be completed.  Applications should also address anticipated challenges to meeting milestones and propose potential mitigation or corrective action strategies.  As appropriate to the study, milestones should address accrual goals for women, minorities, and individuals of all ages and any other identified populations for completion of the approved research.  Please see the NIH Policy on Inclusion of Women and Minorities as Subjects in Clinical Research.

Milestones will be refined and finalized in consultation with NIDCR Program Staff at the time of the UG3 and UH3 award, if granted.  The Terms and Conditions for an award under this NOFO will include, but not be limited to, annual milestones.  These items will be carefully assessed, and future support of a trial funded under this NOFO is contingent upon meeting projected milestones, including meeting adequate participant enrollment/retention targets, as appropriate to the research study involved.

Milestones that may be completed during the UG3 include, but are not limited to:

• Development or finalization of tools, methods, applications, algorithms, techniques, etc.  Establishment of the reliability and/or validity of (new) measures.  Acceptability, feasibility, or testing of aspects of the study intervention(s) or procedures.  Development and finalization of the upcoming UH3 clinical protocol and other required documentation.  Required documentation can include a clinical protocol, manual of procedures, clinical quality management plan, data quality management plan, etc. as appropriate.  Templates for such documentation can be seen on the NIDCR website with resources for intervention studies.  Note: A full pilot of the UH3 planned intervention is prohibited in the UG3 planning phase.
• Sample size estimations, effect size analysis, or power analysis.
• Development of fidelity monitoring procedures. 
• Completion of the data management system.
• Preparation of all materials required for regulatory approvals (IRB and applicable oversight committees).
• Finalization of agreements for use of resources available within NIH-funded Clinical and Translational Science Awardees (CTSAs), practice-based research networks, patient, registries, etc., as applicable.
• Preparation of any other documents necessary to implement the trial.

Milestones that must be completed during the UH3 include, but are not limited to:

• Completion of regulatory approvals (e.g., IRB), documents, and site activation activities.
• Registration of clinical trial in ClinicalTrials.gov.
• Finalization of clinical protocol, statistical analysis plan, and other study documents necessary to implement the study.
• Finalization of the data management system.
• Enrollment of the first participant report.
• Enrollment and randomization of 25%, 50%, 75% and 100% of the projected study population.
• Fulfillment of Study Accrual and Retention (SARP) targets.
• Completion of data collection.
• Completion of primary study report.
• Completion of data collection time period.
• Completion of primary and secondary outcome data analyses.
• Completion of final study report.
• Reporting of results in ClinicalTrials.gov per the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.
• Additional milestones, as appropriate.

Applications that lack the Milestone Plan are considered incomplete and will be withdrawn without peer review.

Transition to the UH3 Phase: An administrative review will determine whether the UH3 phase award will be issued, subject to funding availability.  Applicants and recipients of UG3 funding should note that the UG3 award does not guarantee subsequent UH3 funding. 

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

Applicants should refer to NIH's policy on data and safety monitoring (https://grants.nih.gov/policy/humansubjects/policies-and-regulations/data-safety.htm) and the NIDCR Clinical Terms of Award for research involving human subjects.

Describe the study-specific plan to ensure data and safety monitoring, including:

Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of administering the study intervention(s). Include methods to monitor study intervention fidelity and systems to record, report and manage exceptions and deviations. If applicable, describe monitoring of participating facilities such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies, the appropriate reporting to relevant authorities, including but not limited to the IRB of record, Data and Safety Monitoring Board (DSMB) if one is assigned, FDA if applicable, institutional officials and the NIH.

Describe plans to ensure that validated systems and controls are in place to assure the integrity of the clinical trial data being collected; proposed methods and systems for data collection (e.g., paper or electronic data collection systems), data entry, data verification, data validation and adverse event reporting; and the process for locking the final trial dataset for analyses. Describe the data query process and query frequencies and any planned mitigation strategies in the event of noncompliance with data collection processes.

Do not name members of any oversight board in the application. The NIDCR will appoint members of any oversight committees after consultation with the investigators.

Section 4 - Protocol Synopsis

4.3 Statistical Design and Power

In addition to the information requested in the SF424 (R&R) Application Guide instructions and “Section 2 – Milestone Plan” above, describe the plans for handling missing data.

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 and responsiveness by NIDCR, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applications that do not include a Study Timeline and Milestone Plan will be considered incomplete and 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 procedures outlined in NIDCR’s Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs and 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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 the primary responsibility for:

• Providing scientific leadership for all aspects of the study, including planning, 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 and the NIDCR Policy on Data and Safety Monitoring 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 having primary rights to the data 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;
• Making all study materials, procedure manuals, and final datasets available in the public domain, managed by the awardee institution.  Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with NIH 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:

• Consult with the PD(s)/PI(s) regarding UG3 milestones for the planning phase of the study and annual milestones for the UH3 implementation phase;
• Serve as a resource to provide scientific/programmatic support during research study planning and implementation by providing input on experimental and clinical approaches and study protocols, and advising in the management and operational aspects of study development and implementation;
• Participate on teleconferences with PDs/PIs and dental PBRN personnel to monitor study development and implementation progress, adherence to the study protocol, conduct of the study, and recruitment and retention of study participants;
• Review the progress of the study 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;
• Periodically review reports of study progress. NIDCR staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government right of access consistent with HHS, PHS and NIH policies.

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;
• Perform other duties required for normal program stewardship of grants.

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

NIDCR may convene a Data and Safety Monitoring Board (DSMB) to periodically review and evaluate accumulated study data for participant safety; study conduct and progress; and, when appropriate, efficacy. The DSMB may make recommendations to NIDCR concerning the continuation, modification, or termination of the trial.

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

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]

Jill Mattia, Ph.D.
Director, Assessment, Technology, and Treatment Outcomes Research Program
National Institute of Dental and Craniofacial Research (NIDCR) 
Telephone:301-451-7770
Email: [email protected]

Yasaman Shirazi, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: [email protected]

Gabriel Hidalgo
Acting Chief, Grants Management Branch 
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.