To support competing renewal or competitive revision of ongoing clinical trials supported by the National Institute of Dental and Craniofacial Research (NIDCR)

Funding Opportunity Number: PAR-25-062. Assistance Listing: 93.121. Funding Instrument: CA. Category: HL.

PAR-25-062: Continuation or Revision of NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UH3 Clinical Trial Required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Dental and Craniofacial Research ( NIDCR ) Funding Opportunity Title Continuation or Revision of NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UH3 Clinical Trial Required) UH3 Exploratory/Developmental Cooperative Agreement Phase II March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. December 02, 2024 - NIDCR Behavioral and Social Intervention Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required). See Notice PAR-25-188 .

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) will accept applications for competing renewal or competitive revision of ongoing clinical trials supported by the National Institute of Dental and Craniofacial Research (NIDCR).

Extension of an ongoing clinical trial through a competing renewal application will be supported when there is need for additional time to complete the trial or when an extended period of follow-up is well justified to assess longer term outcomes. Competitive revisions will be supported when there is compelling justification for modifying the scope of the ongoing clinical trial.

NIDCR strongly encourages applicants to contact the Scientific/Research contact assigned to the ongoing clinical trial for which they are planning a competing renewal or competitive revision prior to submitting an application to this NOFO.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

Required Application Instructions 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 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 accept applications for competing renewal of ongoing clinical trials supported by NIDCR or competitive revisions proposing to modify the scope of ongoing NIDCR-supported clinical trials.

Extension of an ongoing clinical trial via a competing renewal will be considered when there is a need for additional time to complete the trial or when an extended period of follow-up is well justified to assess longer term outcomes. Competitive revisions will be considered when there is compelling justification for modifying the scope of an ongoing clinical trial.

Clinical trials appropriate for this NOFO are those proposing diagnostic, prevention, management or treatment approaches to test a drug, biologic, device, procedure, or a behavioral or social intervention for dental, oral, or craniofacial diseases or conditions, including trials for any phase of testing for a Food and Drug Administration (FDA)-regulated product.

Clinical trials that involve behavioral or social sciences research at other stages of the intervention-development process also are appropriate. For example, the addition of a theoretically-driven model on interpersonal processes that facilitate healthier behavior change and adherence to an existing clinical trial not premised on interpersonal relationships is an example of a competitive revision to a behavioral/social clinical trial.

An application that proposes additional longitudinal follow-up to explore ongoing behavioral adherence to an intervention with overwhelming oral public health impact is an example of a competing renewal.

Prior to submitting applications to this NOFO, all applicants are strongly encouraged to consult with the Scientific/Research contacts for the ongoing clinical trial to determine whether a competing renewal or competitive revision application is of interest to NIDCR. Early contact (e.g., 12 weeks prior to submission) is encouraged.

This period of time provides an opportunity for NIDCR staff to discuss the scope and goals, and to provide information and guidance to potential applicants. The NIDCR is committed to identifying effective preventive, diagnostic, and treatment approaches for dental, oral, and 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 and 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, surgical planning tools, or enhancements to electronic health records) 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.

Each UH3 Clinical Trial Cooperative Agreement award will support the implementation of a single clinical trial. Competing renewal applications will be considered when there is rationale to support extension of an ongoing clinical trial, when additional time is needed to complete the trial or when an extended period of follow-up is well justified to assess longer term outcomes.

Competing renewal applications should provide strong justification and a detailed timeline to support the need for additional time to complete the trial or to assess longer term outcomes. Competitive revision applications will be considered when there is a compelling rationale to modify the scope of the clinical trial.

Any new aim(s) proposed in the grant application should be fully powered to test the hypothesis(es) and may require additional data collection, specimen collection, or procedures. The proposed modification may use some or all of the ongoing clinical trial population.

The NIDCR will be substantially involved with the UH3 awardees as a partner in providing overall scientific and operational guidance, consistent with the Cooperative Agreement mechanism. The NIDCR expects clinical trials 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. 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 submitted the appropriate investigational application to the FDA prior to submitting the grant application. 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.

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/ .

Projects funded under this NOFO must be driven by well-defined, annual milestones that must be completed during clinical trial implementation. 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.

Continued funding during the UH3 project period will be dependent upon meeting annual UH3 milestones, and it is expected that the study will be completed within the UH3 project period. 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 trial implementation activities that involve human subjects. 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.

Section II. Award Information 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. Application Types Allowed 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). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets 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 scope of the proposed project should determine the project period. The maximum project period is 5 years.

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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations 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 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.

Eligible Individuals (Program Director/Principal Investigator) 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.

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 .

3. Additional Information on Eligibility 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission 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. 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. All instructions in the How to Apply- Application Guide must be followed. The applicant should estimate the costs for clinical trial implementation based on the scope of work described in the application.

Budget justifications must be included. The length of the project period should reflect the actual needs of the project. The maximum project period is 5 years; project periods of less than 5 years will be accepted.

If parts of the costs of the trial are to be provided by sources other than NIDCR, 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. PHS 398 Cover Page Supplement 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: The significance, biological and clinical relevance of the proposed study must be stated clearly. It should be supported by the following: A clear statement of the question(s) the study will address and its importance.

The scientific rationale and clinical need for the study, including an assessment of previous preclinical and/or clinical studies and their quality (if applicable). The potential for the study results to impact knowledge or clinical practice. If the proposed study is a Phase III clinical trial , information about the generalizability of potential findings to US populations.

For renewal applications, provide strong justification for why additional time is needed to complete the trial or why extended follow-up for longer term outcomes is important. For revision applications, provide a description of what additional knowledge will be gained in the modified study scope and compelling rationale for the proposed study scope modification.

Present a compelling argument of how the proposed trial will shift clinical practice or inform health care policy. The application should describe any novel theoretical concepts, approaches or methodologies, instrumentation or interventions that will be used in the proposed clinical trial.

Address the feasibility of recruiting (or retaining if participants have already been enrolled in the trial) participants who are eligible for the proposed research. For an application proposing a multi-site study, applicants are expected to provide evidence that each recruiting center has access to sufficient study participants who meet the eligibility criteria.

Provide an overview of the proposed study design that must justify the selected trial elements provided in the Protocol Synopsis, including: Provide a translation of the clinical question into a statistical hypothesis. Rationale for the selected trial design/intervention model (e.g., single-group, parallel, cluster-randomized, factorial) and allocation method. Justification for the selected study Phase.

For example, there should be adequate evidence from previous studies that an intervention should be tested in a Phase III, multi-center trial. Rationale for selection of the intervention to be tested and a description of how and at what frequency the intervention will be administered.

For behavioral interventions, demonstration that an intervention engages the mechanism of action target(s) it intends to, and that target engagement can be measured. Methods to be used to ensure masking or minimize bias if complete masking is not possible. Justification for selection of the primary and secondary outcome measures and a description of how the outcome variables will be collected and the criteria for measuring the outcomes.

Description of the study population, including the sample size, pertinent demographic information, required health status or disease condition, and geographic location. Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in Section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information form.

Description of the proposed effect size of the study expressed in terms of a clinical outcome (e.g., 25% reduction in caries increment). Discuss potential biases or challenges in the proposed trial and how they will be minimized and/or addressed.

Progress of Ongoing Clinical Trial: Provide a summary of the ongoing clinical trial's progress including attainment of enrollment/randomization and retention targets, and the initial timeline for study completion. Describe any challenges or delays and corrective action strategies utilized by the team in the prior funding period.

Describe any changes that have been made to the study design, sample size, or power calculations during the course of the prior funding period. For renewal applications, describe the reasons for why the trial was not completed in the prior funding period and why additional time is needed to complete the trial or to obtain longer term outcomes.

For revision applications, provide a clear description of additional data collection, specimen collection, procedures, and/or study participants needed to attain the proposed aim(s) associated with the modified study scope. Without duplicating information in biosketches, describe the expertise of the study team and the team’s ability to develop, manage and implement the planned study and perform appropriate analyses of data collected.

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: All applications, regardless of the amount of direct costs requested for any one year, should address: A plan to make study materials and procedures manuals (data collection instruments, study protocols) available in the public domain.

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 3. 3 Data and Safety Monitoring Plan 4. 3 Statistical Design and Power 5.

1 Other Clinical Trial-related Attachments 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 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. The filename "Study Timeline and Milestone Plan" should be used to name this attachment, which should include both the Study Timeline and Milestone Plan .

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.

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 annual UH3 milestones that will be completed during the UH3 implementation phase.

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 UH3 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 clinical trial implementation include, but are not limited to: Finalization of clinical protocol, statistical analysis plan, and other study documents necessary to implement the study Finalization of a Study Accrual and Retention Plan (SARP), including a timeline for study participant accrual and retention goals Finalization of the data management system Completion of regulatory approvals Registration of clinical trial in ClinicalTrials.

gov Enrollment of the first participant Enrollment and randomization of 25%, 50%, 75% and 100% of the projected study population Completion of data collection time period Completion of primary and secondary outcome