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
NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
Reissue of PAR-18-547
Related Notices

See Notices of Special Interest associated with this funding opportunity

See Notices of Special Interest associated with this funding opportunity.

  • April 23, 2021 - NIDCR Policy on Applications for Investigator-Initiated Clinical Trials. See Notice NOT-DE-21-004.
  • March 19, 2021 - Notice of Correction to R&R Budget Form for PAR-21-160. See Notice NOT-DE-21-002.

Funding Opportunity Announcement (FOA) Number
PAR-21-160
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.121
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) 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 FOA 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 FOA 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 described in the application, following the instructions described in this FOA. 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. 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 FOA.

Key Dates

Posted Date
March 05, 2021
Open Date (Earliest Submission Date)
May 08, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
June 08, 2021 July 08, 2021 September 07, 2021 * November 2021 January 2022 April 2022
October 05, 2021 November 05, 2021 January 07, 2022 * March 2022 May 2022 July 2022
February 08, 2022 March 08, 2022 May 07, 2022 * July 2022 October 2022 December 2022
June 07, 2022 July 07, 2022 September 07, 2022 * November 2022 January 2023 April 2023
October 04, 2022 November 04, 2022 January 07, 2023 * March 2023 May 2023 July 2023
February 07, 2023 March 07, 2023 May 07, 2023 * July 2023 October 2023 December 2023
June 06, 2023 July 06, 2023 September 07, 2023 * November 2023 January 2024 April 2024
October 03, 2023 November 03, 2023 January 07, 2024 * March 2024 May 2024 July 2024
February 06, 2024 March 06, 2024 May 07, 2024 * July 2024 October 2024 December 2024

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

Expiration Date
May 08, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

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 FOA to support investigator-initiated clinical trials. This FOA 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.

Projects funded under this FOA must be driven by well-defined milestones to be completed during the planning phase and those to be completed during the clinical trial implementation phase. Toward the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request for the UH3 clinical trial implementation phase. The UH3 transition requests will undergo administrative review by NIH staff to determine whether an award will be made for the implementation phase. Transition decisions are based on success in meeting study 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 FOA 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 craniofacial, oral, and dental 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.

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 oral diseases and conditions. Further, clinical trials determine whether interventions are safe, feasible, and acceptable to patients. Clinical studies to evaluate clinical laboratory tests or devices (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 FOA.

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. The study development activities and study implementation plans should be well-developed, and the final design of the UH3 clinical study should be described in the UG3/UH3 grant application. Projects funded under this FOA must be driven by well-defined milestones to be completed during the planning phase and those to be completed during the clinical trial implementation phase. 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 submitted the appropriate investigational application to the FDA prior 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:

  • Clinical trials to determine impactful innovations to dental practice that reduce the risk of highly transmissible and virulent pathogens such as SARS-CoV-2 and ensure the safety of personnel and patients in dental practices;
  • Interventions to understand racial, ethnic, and/or sex/gender differences in dental care recommended and/or received;
  • Clinical trials testing tissue regeneration therapies to repair or replace dental, oral or craniofacial tissues;
  • Clinical trials involving chemotherapeutic, pharmacologic, gene therapy, cell-based therapies or other interventions to prevent and/or treat oral and craniofacial diseases or disorders;
  • Clinical trials testing new preventive or treatment therapies for periodontal diseases or dental caries, especially in populations with high unmet need;
  • Clinical trials testing the ability of oral biosensors/biodevices to diagnose, assess risk and monitor disease;
  • Clinical trials focusing on the treatment of HIV/AIDS associated oral complications;
  • Clinical trials testing therapies to prevent or treat oral candidiasis, oral herpes virus infections, or other oral infections that occur in those with congenital or acquired immune dysfunction;
  • Clinical trials testing therapies for oral manifestations of systemic diseases in medically complex patients, including those with cleft lip / cleft palate;
  • Clinical trials to optimize opioid risk mitigation clinical tools, such as those encouraging the use of prescription drug monitoring programs (PDMPs) and other reminders prior to prescribing opioids for acute pain management;
  • Clinical trials of interventions to prevent or manage salivary dysfunction; and
  • Clinical trials testing pain management strategies for temporomandibular dysfunction and other orofacial pain conditions.

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, 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 subject population to determine recruitment potential for the future trial. The UG3 phase cannot be used to test for intervention safety or efficacy.

Activities supported during the UG3 phase may include, but are not limited to, development of the following:

  • A final clinical protocol following International Conference on Harmonisation (ICH) E6 Good Clinical Practice Consolidated Guidance, prepared using the NIDCR interventional protocol template or the NIH-FDA protocol writing tool if proposing a Phase II or Phase III clinical trial that requires an investigational new drug (IND) or investigational device exemption (IDE) application;
  • The Manual of Procedures (MOP), which should include a detailed description of study procedures to ensure consistency of data collection across sites and processes for validation and quality control of any non-standard clinical or laboratory/mechanistic testing that will be performed;
  • The final statistical analysis plan;
  • Final data collection instruments (case report forms) that are ready to be programmed into an electronic data management system;
  • The consent form(s) and assent form(s), if applicable;
  • The Clinical Investigators Brochure (IB) or equivalent, if applicable;
  • A plan to administer study agent or deliver intervention, train interventionalists, and monitor intervention delivery;
  • The final quality management and data management plans; and
  • A recruitment/enrollment and retention plan for the clinical study, including strategies should enrollment or retention not meet specified metrics.

Milestones and UG3/UH3 Transition

All projects must be driven by well-defined milestones for the UG3 planning phase and annual milestones for 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. All UG3 grants will need to meet milestones to have an opportunity to move to the UH3 implementation phase. At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request package, which will undergo an administrative review to determine whether the study will be awarded funding for the UH3 clinical trial implementation phase.

Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee funding of the UH3 phase. Transition to the UH3 phase is dependent on having successfully met the UG3 planning 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.

UH3 Clinical Trial Implementation Phase

The UH3 funding period will provide 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 study will be completed within the UH3 grant period. The trial outcome measure(s) must be clinically meaningful and important to stakeholders including patients and health care providers. The NIDCR expects clinical trials supported during the UH3 phase to be hypothesis driven, milestone-defined, and have the potential for high impact within the research mission of the NIDCR. The clinical trial must meet all applicable NIH, Food and Drug Administration (FDA), and Office for Human Research Protections (OHRP) policy requirements.

Additional Information

The proposed clinical study must meet all applicable NIH and Office for Human Research Protections (OHRP) policy requirements. Awardees are required to comply with the NIDCR Clinical Terms of Award and the NIDCR Policy on Data and Safety Monitoring 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 protocol writing tool 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 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 FOA.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support 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 FOA.

Application Types Allowed
New
Renewal
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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.

Award Budget

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.

Award Project Period

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 FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

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

Federal Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 not allowed. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Yasaman Shirazi, PhD
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

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

1.Milestone Plan. The filename "Milestone Plan" should be used to name this attachment.

A milestone is defined as: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. The Milestone Plan must describe objective, measurable milestones with separate milestones for the UG3 and UH3 phases. The milestone plan must include clearly stated milestones that will be reached at the end of the UG3 planning phase and annual milestones that will be completed during the UH3 implementation phase. The milestone plan should address anticipated challenges to meeting milestones and propose potential mitigation or corrective action strategies.

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. Future support of a study funded under this FOA is contingent upon adequate participant enrollment based on projected milestones.

  • Milestones that may be completed during the UG3 phase include, but are not limited to:
    • Demonstration that the necessary study population is available at the clinical sites and finalization of plans to add or drop clinical sites if needed
    • Collection of any data to determine feasibility of study procedures and/or study intervention and establish a timeline for accrual of study participants
    • Finalization of plans to obtain study agent(s), if applicable
    • Finalization of agreements for use of resources available within CTSAs, patient registries, community partner sites, etc.
    • Finalization of clinical protocol
    • Acceptance of the protocol by NIDCR
    • Finalization of data collection instruments that are ready to be programmed into an electronic data management system
    • Finalization of study-related documents, including consent/assent documents, that are ready for submission to IRB and/or applicable oversight committees
    • Finalization of the statistical analysis plan
    • Near-final drafts of all documents necessary to implement the study (e.g., Manual of Procedures, study procedure/training documents for practitioners, study-specific data management plan)
    • Submission of regulatory documents to the FDA for FDA-regulated interventions
  • Milestones that may be completed during the UH3 phase include, but are not limited to:
    • Finalization of the data management system
    • Registration of clinical trial in ClinicalTrials.gov
    • Study activation
    • 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 outcome 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.
SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Budget

All instructions in the SF424 (R&R) 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.

If parts of the costs of the study are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These 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.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) 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:

  • 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.

Investigator(s):

  • Describe the expertise of the study team and the team’s ability to plan and implement the planned study and perform appropriate analyses of data collected.

Innovation:

  • 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.

Approach:

The Approach section should have a clear demarcation of the UG3 and UH3 portions of the application.

For the UG3 phase:

  • Describe the study development activities planned for the UG3 phase.

For the UH3 phase:

  • Address the feasibility of recruiting participants who are eligible for the proposed research. For an application proposing a multi-site study, applicants are expected to provide evidence that each recruiting center has access to sufficient study participants who meet the eligibility criteria.
  • Provide 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, cross-over, 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.
    • 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.

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 SF424 (R&R) Application Guide.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address: 1) A Data Sharing Plan describing the plan to make final datasets available in the public domain, managed by the grant applicant institution, and 2) a plan to make study materials and procedures manuals (data collection instruments, study protocols) available in the public domain.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

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. 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).

2.7 Study Timeline

Applicants should provide separate project performance timelines for the UG3 planning phase and the UH3 implementation phase of grant period. The UG3 timeline should include the estimated time for completion of each of the UG3 milestones (see "Other Attachments"). UH3 timeline should include the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis. Project performance timelines 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.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

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. Describe the methods and systems to ensure data confidentiality and subject privacy.

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 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:

  • Screening Visit (time point): Sign consent form, assess eligibility criteria, review medical/dental history, review concomitant medications;
  • Baseline Visit (time point): Confirm eligibility, obtain informed consent if needed, randomize, obtain baseline clinical and/or laboratory assessment(s), collect biospecimens, obtain patient-reported outcomes;
  • Interim Study Visit(s) (time points): Provide intervention(s), obtain clinical and/or laboratory assessment(s), collect biospecimens, obtain patient-reported outcomes;
  • Final Study Visit (time point): Obtain final clinical and/or laboratory assessment(s), collect end-of-study biospecimens, obtain patient-reported outcomes.

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.

  •  
  • Describe plans to standardize study processes, train study staff, and monitor adherence to the clinical protocol, standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)
  • Describe the methods and systems for data collection (e.g., Case Report Forms/CRFs), including timely data entry, and the frequency and processes of review to ensure complete, accurate, and consistent data collection.
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 SF424 (R&R) Application Guide must be followed.

Do not enter a delayed onset study, as the UH3 trial should not be considered a delayed onset study.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 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 SF424 (R&R) Application Guide.

Applicants must follow the NIDCR-specific instructions for applications requesting $500,000 or more in direct costs for any year.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions 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.

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.

Overall Impact

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 review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

If applicable, is the proposed effect size of the trial clinically meaningful? For Phase III trials, is there potential for generalizability of study findings to US populations?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Are the primary and secondary outcome variables described, justified, and is there an appropriate description of how they will be collected and measured?

UG3 Planning Phase

Are there clear plans to obtain required study agent(s)? Are the plans clear for developing a final study protocol, final data collection instruments (e.g. case report forms) and other study-related documents? Are there appropriate plans for the final determination of clinical sites and obtaining necessary populations for the future trial? Is there an adequate discussion of potential challenges that are anticipated during planning and study implementation, and how they will be addressed?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

 

 

Schedule of Events

Is the Schedule of Events for an individual study participant appropriate for the study design and data to be collected? Are the procedures and frequency of visits reasonable and feasible as described in the Schedule of Events?

Quality Management Plan

Are the processes in the Data Quality Management Plan adequate to assess and document adherence to clinical trial procedures and ensure the quality of data collection procedures?

Other Attachments

Regarding the additional document included as "Other Attachments":

Milestone Plan

Are the milestones and activities clearly stated? Are appropriate, measurable milestones clearly defined for the UG3 development phase? Is it likely that the investigator team will meet these milestones within the proposed UG3 project period?

Are appropriate, measurable annual milestones clearly defined for the UH3 implementation phase? Are the annual milestones feasible to be accomplished during the proposed UH3 project period? Does the application address contingency plans in the event the UG3 and/or UH3 milestones are not achieved?

Study Timeline

Is the project performance timeline for the UG3 phase feasible to accomplish the proposed study development activities within the proposed timeframe? Is the project performance timeline for the UH3 phase feasible to implement and complete the study within the proposed timeframe?

Does the UH3 timeline include the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis?

 

Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

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

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. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Dental and Craniofacial Research Council. 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.

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 VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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 awardee 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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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 (DHHS) grant administration regulations at 45 CFR Part 75, 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 the NIH as defined below.

The PD(s)/PI(s) will have 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 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 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 awardees 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 composed of 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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Dena Fischer, DDS, MSD, MS
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4876
Email: dena.fischer@nih.gov

Peer Review Contact(s)

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: yasaman.shirazi@nih.gov

Financial/Grants Management Contact(s)

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

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.

Authority and Regulations

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 45 CFR Part 75.


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