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

New

Related Notices
Funding Opportunity Announcement (FOA) Number

PAR-18-547

Companion Funding Opportunity

none

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.121

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to seek UG3/UH3 phased cooperative agreement research applications to plan and implement clinical trials within the mission of NIDCR. 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 of up to five years (UH3). Only UG3 projects that have met the scientific milestones and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.  The UG3 phase will permit the Program Director/Principal Investigator to finalize the study team and will support activities to develop: the final clinical protocol; the Clinical Investigator’s Brochure (or equivalent), if needed; the data management system and other tools for data collection and quality management, safety and operational oversight plans; recruitment and retention strategies; and other essential documents such as the Manual of Procedures for the subsequent clinical trial in the UH3 phase. The UG3 planning phase is not designed for pre-clinical studies with animals, the collection of preliminary data on the efficacy of the intervention (such as pilot testing), or the collection of observational data from humans to support the rationale for a clinical trial.  Evaluation of the potential subject population to determine individuals’ eligibility for participation in the future UH3 trial is allowed in the UG3 phase but not required. The UH3 phase of the award will support the conduct of one investigator-initiated clinical trial.

Key Dates
Posted Date

December 22, 2017

Open Date (Earliest Submission Date)

January 23, 2018

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

New applications - February 23, June 6, and October 4 of 2018; February 6, June 6 and October 8 of 2019; February 6, June 8, and October 6 of 2020 by 5:00 PM local time of applicant organization. Revised applications -  July 6 and November 6 of 2018; March 6, July 8 and November 6 of 2019; March 6, July 7 and November 6 of 2020, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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.

AIDS Application Due Date(s)

May 7, September 7 of 2018; January 7, May 7, September 7 of 2019; January 7, May 7, September 7 of 2020; January 7 of 2021 by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.

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.

Scientific Merit Review
Advisory Council Review
Earliest Start Date
Expiration Date

January 8, 2021

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the 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 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. 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. 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 funding opportunity to support both the planning activities and the implementation of an investigator-initiated clinical trial. The UG3 phase of the NIDCR Clinical Trial Planning and Implementation Grant (UG3/UH3) will support the comprehensive planning of and document development for an investigator-initiated clinical trial, including those for any phase of testing for an FDA-regulated product. The transition to the UH3 phase is dependent on NIDCR program priorities, availability of funds, and an administrative review to determine if the UG3 planning milestones have been met successfully. The UG3 phase cannot be used to pilot test an intervention or collect data to support the rationale for a clinical trial.  The final design of the UH3 clinical trial should be defined in the application. Investigators needing to pilot test their intervention to develop the final clinical trial design should apply to a different funding opportunity announcement, or propose a small trial for the UH3 phase. 

    Background

    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. The purpose of a clinical trial is to determine whether an intervention is efficacious or effective in changing disease incidence or severity or in treating a disease.  In addition, clinical trials determine whether interventions are safe, feasible, and acceptable to patients. Clinical research involving an intervention to modify individual, family or group behavior to change a health outcome also fits the definition of a clinical trial. 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 participant enrolled in the trial, and that decision could possibly affect a health outcome.

    NIDCR is interested in supporting clinical trials that are designed to answer questions based on a strong scientific premise that are carried out through a robust approach. Most clinical trials supported by the NIDCR are investigator-initiated clinical trials, conducted at single or multiple sites. The trial may be supported by a coordinating center, central laboratories and/or other specialized services. To adequately plan and finalize the details for implementation of the clinical trial, investigators need time to prepare. Therefore, a UG3/UH3 award will support the planning phase (UG3) and the implementation phase (UH3) of a single trial that has met the scientific milestones and feasibility requirements for transition. 

    Applications designed to test the efficacy of a behavioral intervention will not be supportedby this FOA.

    Scope of the UG3/UH3 FOA

    Each UG3/UH3 NIDCR UH3 Clinical Trial Implementation Cooperative Agreement award will only support the planning and implementation of a single clinical trial.

    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 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 therapies to treat 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 testing non-opiate therapies to reduce post-operative pain and swelling after dental procedures;
    • 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 treatments for oral mucositis and other oral manifestations of systemic diseases;
    • Clinical trials comparing therapies for oral diseases in medically complex patients, including those with cleft lip / cleft palate;
    • Clinical trials of interventions to prevent or manage salivary dysfunction; and
    • Clinical trials testing treatments for temporomandibular dysfunction and other orofacial pain conditions.

    Clinical Trial Planning Phase (UG3)

    The UG3 grant award will provide one year of support for finalizing the protocol and preparing other documents to implement the clinical trial. The UG3 award is not designed for the collection of preliminary data (either clinical or pre-clinical animal studies) about the efficacy of an intervention, or the collection of prospective data to support the rationale for a clinical trial. Planning activities such as evaluating the potential study population to determine the number of subjects at a site that would fulfill eligibility criteria for the UH3 trial are allowed.

    Applicants and recipients of UG3 funding should note that the UG3 award does not guarantee subsequent UH3 funding for the clinical trial.

    Examples of activities supported during the UG3 phase include, but are not limited to, developing the following:

    • A final clinical protocol following International Conference on Harmonisation (ICH) E6 Good Clinical Practice Consolidated Guidance, prepared using the standard NIDCR interventional protocol template (see NIDCR Toolkit for Clinical Researchers) or the NIH-FDA protocol writing tool (https://osp.od.nih.gov/clinical-research/clinical-trials/) if proposing a Phase 2 or Phase 3 clinical trial that requires an investigational new drug (IND) or investigational device exemption (IDE) application.
    • The Manual of Procedures (MOP) including a detailed description of study procedures and process details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed;
    • The final statistical analysis plan;
    • The consent form(s) and, if applicable, assent form(s);
    • The Clinical Investigators Brochure (IB) or equivalent, if applicable;
    • A plan for the administration of study agent(s), if applicable;
    • Detailed description of Roles and Responsibilities of study personnel;
    • The final quality management and data management plans; and
    • Strategies to put in place should enrollment or retention for follow up not meet specified metrics.

    Clinical Trial Implementation Phase (UH3):

    The objective of the year 2 to year 6 UH3 implementation phase is to conduct the clinical trial in accordance with activities planned in the UG3 phase. 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 of Human Research Protections (OHRP) policy requirements. 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. Guidance documents can be found at http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm219433.htm#

    Milestones and UG3/UH3 Transition

    Projects must be driven by well-defined milestones for the planning phase (UG3) and annual milestones for the clinical trial implementation phase (UH3). It is understood that the proposed milestones for the UH3 phase may be revised as activities in the UG3 phase progress. In the event of an award, the PD/PI and NIH will negotiate a final list of milestones for each year of support.

    At 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 request will undergo an administrative review to determine whether the study will be awarded the implementation phase (UH3).

    To transition to the UH3 phase, the documents created during the UG3 phase must be sufficient to launch the clinical trial, i.e., the study should be ready to begin recruitment as soon as the oversight committee and Institutional Review Board (IRB) approvals are received, and study staff training is completed. The NIDCR will only support clinical trials that are developed using rigorous designs, with full written documentation of all procedures necessary for the trial. The quality of the planning, design, and documentation products for the clinical trial are given key consideration when the NIDCR considers the transition to the UH3 clinical trial implementation phase.

    Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 clinical trial implementation phase.  UH3 funding is dependent on NIDCR program priorities and availability of funds. In addition, applicants should understand that transition to the UH3 phase of the project will occur only if an administrative review process determines that the UG3 planning milestones have been successfully met, and that the UH3 phase can proceed with confidence of success.

    Additional Information

    Awardees are required to comply with the NIDCR Clinical Terms of Award for any planning phase activities that involve human subjects and all subsequent UH3 studies. It is recommended that applicants use the NIDCR tools and templates for development of the clinical trial documents. The details can be found at the following websites: NIDCR Clinical Terms of Award and NIDCR Toolkit for Clinical Researchers.  Implementation of the Clinical Terms of Award ensures that the conduct of the clinical trial meets widely-accepted standards.

    Applicants are encouraged to read "NIDCR Clinical Monitoring Guidelines" for an overview of the practice of clinical monitoring.

    Applications that propose multi-site studies with multiple domestic sites are subject to the new NIH Single IRB policy as indicated in NOT-OD-16-094.

    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
    Resubmission
    Revision

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    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 are not limited for the UH3 phase, 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 in response to 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)

    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)
    • 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) (formerly CCR) – 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. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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

    Buttons to access the online ASSIST system or to download application forms 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 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.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    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.

    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.

    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: 

    The research plan should provide the background and scientific justification for the trial, and should address the following.

    Research Strategy:

    Innovation:

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

    Significance: The significance, biological and clinical relevance of the proposed trial must be stated clearly. It should be supported by the following:

    • Information about the generalizability of potential findings to US populations if this is a Phase 3 trial.
    • Information adequate to determine the significance and timeliness of, as well as the need to perform, the trial. This may include preliminary data, clinical and/or preclinical studies, information in the literature, or knowledge of biological mechanisms.

    The Research Strategy should provide justification for the selected trial elements provided in the Protocol Synopsis and include:

    • A summary of the clinical trial's objectives describing the scientific rationale and clinical need for the trial, and an assessment of the previous preclinical and clinical studies and their quality.
    • The translation of the clinical question into a statistical hypothesis;
    • Rationale for the selected study population, including justification for exclusions of children or other age groups such as those 65 years and older. The study population should be scientifically justified.
    • An overview of the proposed study design that must justify the following:
    • Primary Purpose (e.g., Treatment, Prevention, Diagnostic, etc.)
    • Scientific rationale and justification for the selection of an intervention’s dose, frequency and route of administration;
    • Justification for the selected Phase. For example, there should be adequate evidence from previous trials that an intervention should be tested in a Phase 3, multi-center study.
    • Rationale for the interventional model (e.g., single-group, parallel, cross-over, factorial) and allocation method. 
    • Methods to be used to ensure masking or minimize bias if complete masking is not possible.
    • Justification for selecting the primary and secondary outcome variable(s), including an explanation of the relevance to the clinical and statistical hypothesis being tested and
    • The proposed effect size of the study expressed in terms of a clinical outcome (e.g., 25% reduction in caries increment).
    • A discussion of potential biases or challenges in the trial and how they will be addressed and minimized.

    The NIDCR interventional protocol template (see NIDCR Toolkit for Clinical Researchers) has further information about individual components that should be discussed in the Research Strategy and the Protocol Synopsis. Those planning Phase 2 or Phase 3 clinical trials that require investigational new drug (IND) or investigational device exemption (IDE) applications should provide elements that are consistent with the requirements of the Food and Drug Administration (FDA) IND or IDE. A protocol template for such studies can be found at https://osp.od.nih.gov/clinical-research/clinical-trials/. 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.

    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.

    Appendix:

    Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.  

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a 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, with the following additional instructions:

    Only add one study record for the UH3 clinical trial.. The research strategy section of the application should justify the specifics of the trial, such as the proposed intervention, dosage and frequency of the intervention, trial phase, and characteristics of the study population.

    Section 3 - Protection and Monitoring Plans

    3.3 Data and Safety Monitoring Plan

    The Data and Safety Monitoring Plan should include a description of data monitoring activities, such as:

    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., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and query frequencies and any planned mitigation strategies in the event of noncompliance with data collection processes.

    The process for locking the final trial datasets for analysis.

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

    Section 5 – Other Clinical Trial-related Attachments

    5.1 Other Clinical Trial-related Attachments

    Additional Instructions:

     The application must contain the following three attachments (Schedule of Events, Clinical Monitoring Plan and Milestone Plan), prepared according to the instructions below, to provide evidence that the investigator(s) are ready to proceed with a clinical trial. The information provided in the three other Clinical Trial-related Attachments support the Research Strategy and should not duplicate it. The following documents must be uploaded as separate pdf files with the names indicated below.

    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 Clinical Trial (Interventional) Protocol Template.

    Provide the proposed trial’s schedule of events capturing time points and planned activity at study visits. For example:

    Screening Visit (time point): Sign Consent Form, Assessment of Eligibility Criteria, Review of Medical/Dental History, Review of Concomitant Medications  

    Baseline Visit (time point): Confirm eligibility, obtain informed consent if needed, randomize, obtain bio-specimens, obtain baseline clinical and/or laboratory assessment(s), patient-reported outcomes;

    Interim Study Visit(s) (time points): provide intervention(s), obtain clinical and/or laboratory assessment(s): collect bio-specimens, patient-reported outcomes;

    Final Study Visit (time point): Obtain final clinical and/or laboratory assessment(s), collect end-of-study bio-specimens, patient-reported outcomes.

    Applications that lack the Schedule of Events are considered incomplete and will be withdrawn.

    Clinical Monitoring Plan. The filename "Clinical Monitoring Plan" should be used to name this attachment. 

    The Clinical Monitoring Plan helps assure the quality of the proposed clinical trial through clinical monitoring and data monitoring activities. The plan described below is in addition to the application's Data and Safety Monitoring Plan (DSMP) attachment in Section 3 of the Study Record: PHS Human Subjects and Clinical Trial Information that describes how patient safety will be monitored during the trial.

    The purpose of clinical monitoring is to verify that the clinical trial is being conducted and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

    • Describe the frequency of planned monitoring activities (e.g., Study Initiation, Interim Visits, Study Close Out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center) and what data will be reviewed.
    • 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 the study intervention(s), including fidelity monitoring for behavioral interventions.  Include methods to monitor study intervention and system 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, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

    Applications that lack the Clinical Monitoring Plan are considered incomplete and will be withdrawn.

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

    The Milestone Plan must describe separate milestones for the UG3 and UH3 phases.

    Applicants are required to provide detailed project performance and timeline objectives. This attachment must include two sections: those milestones to be completed during the UG3 planning phase and those to be completed during the UH3 phase. The plan should present an overview of the project timeline to achieve the following general milestones, as applicable:

    Milestones to be completed during the UG3 phase:

    Finalization of plans to obtain study agent(s), if applicable

    Finalization of clinical sites, 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 and establish a timeline for accrual of study subjects

    Finalization of agreements for use of resources available within CTSAs, practice-based research networks, patient registries, etc.

    Finalization of clinical protocol

    Acceptance of the protocol by NIDCR

    Regulatory approvals (IRB and applicable oversight committees)

    Completion of the data management system

    Finalization of all documents necessary to implement the trial, such as case report forms and

    Registration of clinical trial in ClinicalTrials.gov

    Milestones to be completed during the UH3 phase:

    Site activation

    Enrollment of the first subject

    Enrollment and randomization, if applicable, of 25%, 50%, 75% and 100% of the projected study population

    Completion of data collection time period

    Completion of primary endpoint and secondary endpoint data analyses

    Completion of final study report

    Reporting of results in ClinicalTrials.gov per the NIH policy on Dissemination of NIH-Funded Clinical Trial Information.

    Applications that lack the Milestone Plan attachment are considered incomplete and will be withdrawn.

    Delayed Onset Study

    All instructions in the SF424 (R&R) Application Guide must be followed. The UH3 study should not be considered a delayed onset trial as it is expected that the proposed study can be described even though it will not start immediately (i.e., delayed start) 

    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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

    Post Submission Materials

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

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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 there a strong scientific premise for the project? 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?

    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? If applicable, is the proposed effect size of the trial clinically meaningful?   

    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 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 children, justified in terms of the scientific goals and research strategy proposed?

    Does the application adequately address the following, if applicable?

    UG3 Planning Phase

    Are there clear plans to obtain any study agents?  Are there clear plans for developing a final clinical protocol and associated documents? Are there appropriate plans for the final selection of the clinical sites and necessary populations for the future study? Is there an adequate discussion of potential challenges that are anticipated during planning and study implementation, and how they will be addressed? 

    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 characteristics of the proposed 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?

    Schedule of Events

    Are the procedures and frequency of visits in the proposed schedule of events for the trial reasonable and feasible? 

    Clinical Monitoring Plan

    Is the clinical monitoring plan adequate to assure the quality of the proposed clinical trial through clinical monitoring and data monitoring activities? Are there plans for handling any deficiencies that are uncovered and, in cases of serious deficiencies, reporting to relevant authorities?

    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 of proposed sites(s) or center(s) to conduct the trial? Are the plans to add or drop enrollment centers, as needed, appropriate?

    If a multi-site trial is proposed, is there evidence of the ability of each individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate, secure 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.

     Study Timeline and Milestones

    Is the study timeline proposed for the UH3 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 appropriate, evaluative milestones clearly defined for the UH3 phase? Are the milestones feasible and quantifiable with regard to specific aims and timeline? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

    Are appropriate, evaluative milestones clearly defined for the UG3 phase, and is it likely that the investigator team will meet these milestones within the proposed project period?

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the six 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 six 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 Children 

    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 children 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 the National Institute of Dental and Craniofacial Research, 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:

    • 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.
    • Will receive a written critique.

    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 grantee’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.

    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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as 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).

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

    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, Grantees, 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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    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 awardees 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 award 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

    The PD(s)/PI(s) will have the following primary responsibilities:

    * All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators are the PD(s)/PI(s)' responsibilities. The awardee 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.

    * The PD(s)/PI(s) will meet NIDCR policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. The NIDCR policy related to monitoring is available at: https://www.nidcr.nih.gov/Research/ToolsforResearchers/Toolkit/DataandSafetyMonitoring.htm. The NIDCR full policy about terms and conditions of awards supporting clinical research is available at the following NIDCR Website: http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/NIDCRClinicalTermsofAward.htm .

    * Upon implementation of the protocol, each study, whether a single entity or a consortium of entities, will follow the procedures required by the protocol regarding study conduct and monitoring, participant management, data collection, and quality control.

    The PD(s)/PI(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

    * The PD(s)/PI(s) will manage 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.

    * The PD(s)/PI(s) will make all study materials and procedure manuals available in the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDCR/NIH.

    * The PD(s)/PI(s) will obtain 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 will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    An NIDCR Program staff member(s) acting as a Project Scientist(s) will be assigned to have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NIDCR staff members may be designated to have substantial involvement. The NIDCR Project Scientist(s) and any other substantially involved staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NIDCR waiver according to the NIDCR procedures for management of conflict of interest. Some Program Officials will also have substantial programmatic involvement. In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek an NIDCR waiver as stated above.

    The main activities of the NIDCR substantially involved staff members include but are not limited to the following aspects:

    * Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones;

    * Assisting and advising awardees with regard to various regulatory and compliance issues;

    * Participating in monthly teleconferences with PDs/PIs to monitor progress and facilitate cooperation;

    * Monitoring progress of the trial towards meeting its primary outcome;

    * Tracking monthly accrual of participants; and

    * Reviewing the progress of the study, and of each participating component, through consideration of the annual reports, site visits, logs, etc. This review may include, but not be limited to, compliance with the study protocol, meeting subject enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

    An NIDCR Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. An NIDCR Medical or Dental Officer will monitor the studies and serve as the Medical Monitor.

    As appropriate to a funded clinical trial the following collaborative responsibilities will be incorporated in the grant award:

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

    Areas of Joint Responsibility include:

    None, all responsibilities are divided between awardees and NIH staff as described above.

    Administrative Review Committee:

    The NIDCR will establish an Administrative Review Committee to assist in determining the transition from the UG3 phase to the UH3 phase. In addition to the Project Scientist and Program Official, the Administrative Review Committee will contain NIH staff not assigned to the award.

    Dispute Resolution:

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel will be convened, and will vote to resolve the dispute. The Dispute Resolution Panel will have three members (with one vote each): a designee of the award governing body chosen without NIH staff input, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two Panel members. This special dispute resolution procedure does not alter the awardee'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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

    Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

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

    Scientific/Research Contact(s)

    J  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 or 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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