National Institutes of Health (NIH)
National Institute of Dental and Craniofacial Research (NIDCR)
See Notices of Special Interest associated with this funding opportunity
See Section III. 3. Additional Information on Eligibility.
This Notice of Funding Opportunity (NOFO) will support UG3/UH3 phased, cooperative agreement research applications to plan and implement clinical trials within the mission of the National Institute of Dental and Craniofacial Research (NIDCR). Studies appropriate for this NOFO are those testing a drug, biologic, device, or procedure to improve dental, oral, or craniofacial diseases or conditions, including trials for any phase of testing for a Food and Drug Administration (FDA)-regulated product. Awards made under this NOFO will initially support a one-year milestone-driven planning phase (UG3), with possible transition to a clinical trial implementation phase (UH3) of up to five years. Progression to the UH3 phase is based on an administrative review and is dependent on success in meeting UG3 milestones, NIDCR program priorities, and availability of funds.
The UG3/UH3 application must be submitted as a single application with the final design of the UH3 clinical trial including detail about the study population, intervention(s), and outcome(s) described in the application, following the instructions described in this NOFO. The UG3 planning phase permits both scientific and operational planning activities, though the planning phase cannot be used to test for intervention safety or efficacy or assess the studys primary outcome. The UH3 phase of the award will support the conduct of one investigator-initiated clinical trial. Applications designed to test behavior change interventions or those used as tools to understand mechanisms of behavior change will not be supported by this NOFO.
30 days prior to the application due date
Application Due Dates | Review and Award Cycles | ||||
---|---|---|---|---|---|
New | Renewal / Resubmission / Revision (as allowed) | AIDS - New/Renewal/Resubmission/Revision, as allowed | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
February 07, 2025 | March 07, 2025 | May 08, 2025 | July 2025 | October 2025 | December 2025 |
June 06, 2025 | July 07, 2025 | September 04, 2025 | November 2025 | January 2026 | April 2026 |
October 07, 2025 | November 06, 2025 | January 06, 2026 | March 2026 | May 2026 | July 2026 |
February 09, 2026 | March 09, 2026 | May 08, 2026 | July 2026 | October 2026 | December 2026 |
June 08, 2026 | July 08, 2026 | September 09, 2026 | November 2026 | January 2027 | April 2027 |
October 08, 2026 | November 09, 2026 | January 08, 2027 | March 2027 | May 2027 | July 2027 |
February 08, 2027 | March 08, 2027 | May 06, 2027 | July 2027 | October 2027 | December 2027 |
June 07, 2027 | July 07, 2027 | September 08, 2027 | November 2027 | January 2028 | April 2028 |
October 07, 2027 | November 08, 2027 | January 06, 2028 | March 2028 | May 2028 | July 2028 |
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.
Not Applicable
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.
IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:
PURPOSE
Improving health through the generation of robust data from well-designed and executed clinical trials is a high priority for the National Institute of Dental and Craniofacial Research (NIDCR). To meet this goal, the NIDCR offers this NOFO to support investigator-initiated clinical trials. This NOFO utilizes a phased, milestone-driven, cooperative agreement mechanism that includes a one-year UG3 planning phase, followed by potential transition to up to a five-year UH3 clinical trial implementation phase. Progression to the UH3 phase is based on an administrative review following submission of a detailed Transition Package request and is dependent on success in meeting UG3 milestones, NIDCR program priorities, and availability of funds. Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 clinical trial implementation phase.
Each UG3/UH3 award will support an individual project, and the UG3 planning and UH3 implementation activities must be submitted as a single application.
Clinical trials appropriate for this NOFO are those proposing diagnostic, prevention, or treatment approaches to test a drug, biologic, device, or procedure for dental, oral, or craniofacial diseases or conditions, including trials for any phase of testing for a Food and Drug Administration (FDA)-regulated product.
BACKGROUND
The NIDCR is committed to identifying effective preventive, diagnostic, and treatment approaches for dental, oral, or craniofacial diseases and conditions. To advance these efforts, the Institute has maintained a clinical trial program for many years and is continuing its support of well-designed clinical trials that test interventions and have the potential to improve dental, oral and craniofacial health across the lifespan.
A clinical trial is defined by NIH as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. Clinical trial designs may be used to establish efficacy or effectiveness of strategies for the prevention, diagnosis, management and/or treatment of dental, oral, or craniofacial diseases and conditions. Further, clinical trials determine whether interventions are safe, feasible, and acceptable to patients. Clinical studies to evaluate clinical or laboratory tests, techniques or tools (e.g., new imaging techniques, diagnostic tests or surgical planning tools) would meet the definition of a clinical trial if the test or tool would be used for making a medical decision about a study participant, and that decision could affect a health outcome.
Applications designed to test behavior change interventions or those used as tools to understand mechanisms of behavior change will not be supported by this NOFO.
SCOPE
Each UG3/UH3 Clinical Trial Cooperative Agreement award will support the planning and implementation of a single clinical trial. The UG3/UH3 funding mechanism supports projects in two phases; awards made under this NOFO will initially support a one-year milestone-driven planning phase (UG3), with possible transition to a clinical trial implementation phase (UH3) of up to five years. Projects funded under this NOFO must be driven by well-defined milestones to be completed during the UG3 planning phase and those to be completed during the clinical trial UH3 implementation phase.
The UG3 study development activities and UH3 study implementation plans should be well-developed and described in the grant application. The final design, study population and sample size including clinical site(s), intervention(s), and outcome(s) of the UH3 clinical trial should be detailed in the UG3/UH3 grant application. Initial funding of the planning phase cooperative agreement does not guarantee support of the clinical trial implementation phase. The NIDCR will be substantially involved with the UG3/UH3 awardees as a partner in providing overall scientific and operational guidance, consistent with the Cooperative Agreement mechanism.
Trials may be supported by a coordinating center, central laboratories and/or other specialized services. Applicants are encouraged to utilize resources (e.g. CTSAs, electronic health records, administrative databases, patient registries, etc.) to increase the efficiency of trial operations. If the application proposes a clinical trial with an investigational drug, biologic or device, the investigators must have received approval for the appropriate investigational application to the FDA prior to transition to the UH3 phase.
Monitoring the degree to which a study intervention is delivered as it was intended (i.e., with consistency or fidelity) is expected for clinical trials research. Fidelity monitoring will ensure the intervention is being delivered in a standardized manner across clinical sites and among interventionist personnel. Fidelity monitoring procedures should be described in the grant application or developed during the UG3 planning phase.
Design, Analysis, and Sample Size for Studies to Evaluate Group-Based Interventions: Investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Such studies may propose a parallel group- or cluster-randomized trial, an individually randomized group-treatment trial, a stepped-wedge design, or a quasi-experimental version of one of these designs. In these studies, special methods may be warranted for analysis and sample size estimation. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.
Examples of clinical trials that might be planned with the UG3 award and implemented with the UH3 award include but are not limited to:
UG3 Clinical Trial Planning Phase
The UG3 planning phase will provide one year of support for operational and scientific planning activities.
Operational planning activities include, at minimum, finalizing the protocol and preparing other documents to implement the clinical trial (e.g., data collection instruments, Manual of Procedures, quality management plan, data management plan). Allowable scientific planning activities include small-scale data collection to assess the feasibility and/or acceptability of a planned intervention and associated study procedures (e.g., acceptability of mode of intervention delivery; feasibility of proposed data collection procedures; preliminary testing of intervention training and fidelity monitoring procedures) and assessment of the study population to determine recruitment potential for the future trial. The UG3 phase cannot be used to test for intervention safety or efficacy or assess the studys primary outcome.
Activities supported during the UG3 phase may include, but are not limited to, the following, expressed as UG3 milestones:
Milestones and UG3/UH3 Transition
All applications must describe well-defined milestones that must be completed during the UG3 planning phase and annual milestones that must be completed during the UH3 clinical trial implementation phase. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. Milestones must be objective, measurable, and achievable. The Terms and Conditions for an award under this NOFO will include milestones that are mutually agreed upon by the awardee institution and NIDCR. All UG3 awards will need to meet all UG3 milestones to have an opportunity to transition to the UH3 implementation phase.
Toward the completion of the UG3 planning phase, the UG3 awardee will be required to submit a detailed Transition Package to request transition to the UH3 clinical trial implementation phase. The Transition Package requests will undergo administrative review by NIH staff to determine whether an award will be made for the UH3 implementation phase. Transition decisions are based on success in meeting UG3 phase milestones, NIDCR program priorities, and availability of funds. The quality of the study-related documents and plans are given key consideration when the NIDCR considers the transition to the UH3 phase. Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 clinical trial implementation phase.
UH3 Clinical Trial Implementation Phase
The UH3 funding period will provide up to five years of support to conduct the clinical trial in accordance with activities planned in the UG3 phase. Continued funding during the UH3 phase will be dependent upon meeting annual UH3 milestones, and it is expected that the clinical trial will be completed within the UH3 grant period. The NIDCR expects clinical trials supported during the UH3 phase to be hypothesis driven, with well-defined milestones, and have the potential for high impact within the research mission of the NIDCR. The trial outcome measure(s) must be clinically meaningful and important to stakeholders including patients and health care providers. The clinical trial must meet all applicable NIH, FDA, and Office for Human Research Protections (OHRP) policy requirements. UH3 activities may include the following operational activities, expressed as UH3 milestones:
Additional Information
The proposed clinical trial must meet all applicable NIH and Office for Human Research Protections (OHRP) policy requirements, and FDA requirements should be followed where applicable. Awardees are required to comply with the NIDCR Clinical Terms of Award for any planning phase activities that involve human subjects and all UH3 studies. It is recommended that applicants use the NIDCR tools and templates for development of the clinical trial documents, located in the NIDCR Toolkit for Clinical Researchers.
Potential applicants are encouraged to review the NIDCR interventional protocol template or the NIH-FDA Phase 2 and 3 IND/IDE clinical trial protocol template if proposing a Phase II or Phase III clinical trial that requires an investigational new drug (IND) or investigational device exemption (IDE) application. These protocol templates have further information about elements that should be included in a clinical trial and described in the Research Strategy and Protocol Synopsis sections of the grant application. Applications proposing to test products must contain information ensuring that the products are produced according to Good Manufacturing Practice (GMP), a system for ensuring that products are consistently produced and controlled according to quality standards.
Applications that propose multi-site studies with multiple domestic sites are subject to the NIH Single IRB policy as indicated in NOT-OD-16-094 and the Revised Common Rule cooperative research provision 45 CFR 46.114.
Delayed onset studies will not be supported by this NOFO.
See Section VIII. Other Information for award authorities and regulations.
Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.
Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.
The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Required: Only accepting applications that propose clinical trial(s).
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets are limited to less than $400,000 in direct costs for the UG3 phase; Application budgets for the UH3 phase are not limited but need to reflect the actual needs of the proposed project.
If the budget exceeds direct costs of $500,000 or more in any year, applicants must follow the NIDCR policy for Grant Applications Requesting $500,000 or More in Direct Costs for Any Project Year.
The total project period may not exceed one year for the UG3 phase and five years for the UH3 phase.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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.
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.
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.
This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.
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:
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.
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.
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:
The letter of intent should be sent to:
Yasaman Shirazi, PhD
Telephone: 301-594-5593
Email: yasaman.shirazi@nih.gov
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.
All instructions in the How to Apply - Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
For the initial UG3/UH3 application, a complete detailed budget is required for both the UG3 phase and the UH3 phase. The applicant should estimate the costs for the UH3 phase based on the scope of work described in the application for the UH3 phase. Budget justifications must be included. The length of the project period should reflect the actual needs of the project. The maximum project period is 6 years; project periods of less than 6 years will be accepted.
If parts of the costs of the trial are to be provided by sources other than NIH, these contributions must be presented in detail in the budget justification. These outsourced 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.
Data and Safety Monitoring Board (DSMB) expenses and activities will be provided by NIDCR if the DSMB is convened by NIDCR.
All instructions in the How to Apply-Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:
Specific Aims
Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 phase and in the UH3 phase. Clearly label them as UG3 Specific Aims and UH3 Specific Aims.
Research Strategy
Significance:
The significance, biological and clinical relevance of the proposed study must be stated clearly. It should be supported by the following:
Innovation:
Approach:
The Approach section should have a clear demarcation of the UG3 and UH3 portions of the application.
For the UG3 phase:
For the UH3 phase:
Investigator(s):
Letters of Support: Letters of support may be included from research collaborators, clinical collaborators, patient organizations, or other groups with whom the investigators propose to work.
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.
The following modifications also apply:
Other Plan(s):
All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:
Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.
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:
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 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 studys 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
Applicants should provide separate project performance timelines for the UG3 planning phase and the UH3 implementation phase of grant period. 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: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be objective, measurable, and achievable. The study timeline must include clearly stated UG3 milestones that will be reached at the end of the UG3 planning phase and annual UH3 milestones that will be completed during the UH3 implementation phase, with separate milestones for the UG3 and UH3 phases. Applications should also address anticipated challenges to meeting milestones and propose potential mitigation or corrective action strategies. Milestones should address accrual goals for women, minorities, and individuals of all ages and any other identified requirements for completion of the approved research.
Milestones may be refined and finalized in consultation with NIDCR Program Staff at the time of the UG3 phase award and the UH3 phase award, if granted. The Terms and Conditions for an award under this NOFO will include Milestones that are mutually agreed upon by the investigators and NIDCR. Annual milestones 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.
Milestones that may be completed during the UG3 planning phase include, but are not limited to:
Milestones that may be completed during the UH3 implementation phase include, but are not limited to:
Applications that lack the Milestone Plan are considered incomplete and will be withdrawn without peer review.
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/or 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 study 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, describe the plans for handling missing data.
Section 5 Other Clinical Trial-related Attachments
5.1 Other Clinical Trial-related Attachments
The application must contain the following two attachments (Schedule of Events, Quality Management Plan), according to the instructions below. The information provided here will be considered by reviewers and is meant to supplement, not duplicate, information provided in the Research Plan or other sections of the Study Record: PHS Human Subjects and Clinical Trials Information form. The following documents must be uploaded as separate pdf files with the names indicated below.
1. Schedule of Events. The filename "Schedule of Events" should be used to name this attachment. Applicants are encouraged to use the sample format (Appendix A) in the NIDCR Interventional (Clinical Trial) Protocol Template.
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.
For example:
2. 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 trial procedures, and to ensure the quality of data collection procedures.
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.
Do not enter a delayed onset study, as the UH3 study should not be considered a delayed onset study.
All instructions in the How to Apply- Application Guide must be followed.
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
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, NIHs 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.
This initiative is not subject to intergovernmental review.
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 organizations 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.
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.
Applicants requesting $500,000 or more in direct costs in any year must follow the NIDCR-specific instructions for applications requesting $500,000 or more in direct costs for any year to seek permission to submit the application.
Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.
Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.
Applicants are required to follow the instructions for post-submission materials, as described in the policy
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.
For this particular announcement, note the following:
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
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 evaluate 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 criterion score.
Significance
Innovation
Specific to this NOFO:
Approach
Rigor:
Feasibility:
Specific to this NOFO:
Investigator(s)
Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.
Environment
Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.
Specific to this NOFO:
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.
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects; 2) adequacy of protection against risks; 3) potential benefits to the subjects and others; 4) importance of the knowledge to be gained; and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, evaluate: 1) the justification for the exemption; 2) human subjects involvement and characteristics; and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.
As applicable, evaluate the full application as now presented.
Not Applicable.
Not Applicable.
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.
For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.
Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
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 National Advisory Dental & Craniofacial Research Council. The following will be considered in making funding decisions:
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 applicants 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 applicants 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.
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.
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 recipients 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).
The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:
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.
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:
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:
An NIDCR Program Official will be assigned. The NIDCR Program Official will:
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 and/or 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:
With the exception of the decision about transitioning to the UH3 phase, 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.
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.
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: GrantsInfo@nih.gov (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: support@grants.gov
Dena Fischer, DDS, MSD, MS
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4876
Email: dena.fischer@nih.gov
Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: yasaman.shirazi@nih.gov
Gabriel Hidalgo, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4630
Email: gabriel.hidalgo@nih.gov
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.