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)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)

Funding Opportunity Title
Feasibility Studies that Explore Healthy and Diseased Temporomandibular Joints (TMJ) using Single Cell Multi-Omic Analyses (UH2/UH3 Clinical Trial Not Allowed)
Activity Code

UH2/UH3 Phase Innovation Awards Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-DE-22-005
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.121, 93.313
Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to encourage feasibility and discovery studies focused on providing foundational knowledge to further studies of cellular and molecular mechanisms underpinning temporomandibular joint disorders (TMJD) pain and tissue dysfunction using single-cell omics approaches. This FOA has goals of identifying cell populations and mapping their effector pathways in TMJD target tissue (e.g., synovial fluid, muscle, skin) as 1) molecular disease classifiers allowing for patient stratification, 2) diagnostic, prognostic, and/or predictive biomarkers, and/or 3) novel therapeutic targets.

The UH2 phase of this FOA will initially support a one-year milestone-driven planning and feasibility phase for all aspects of the clinical research study including planning for participant recruitment, sample collection and processing, and data analysis. The UH3 phase will provide support of up to two years for implementation of the study from human subjects recruitment to single cell data collection and analysis in line with the purpose of this FOA. Applications responding to this FOA must address both UH2 and UH3 phases.

Key Dates

Posted Date
August 12, 2021
Open Date (Earliest Submission Date)
October 10, 2021
Letter of Intent Due Date(s)

October 10, 2021

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 10, 2021 Not Applicable Not Applicable March 2022 May 2022 July 2022

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
November 11, 2021
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: This Funding Opportunity Announcement (FOA) is a phased initiative to support feasibility and discovery studies to provide foundational knowledge to further studies of the mechanisms underpinning temporomandibular joint disorders (TMJD) pain and tissue dysfunction using single-cell omics approaches. These advanced approaches would assist in identifying cell populations and mapping of their effector pathways in TMJD target tissue (e.g., synovial fluid, muscle, skin) as 1) molecular disease classifiers allowing for patient stratification, 2) diagnostic, prognostic, and/or predictive biomarkers, and/or 3) novel therapeutic targets. These feasibility studies are expected to contribute to the goal of delineating cellular and molecular mechanisms that mediate TMJD resolution and homeostasis.

Background: TMJDs are a heterogenous and poorly understood set of painful conditions that manifest in the temporomandibular joint (TMJ), muscles of mastication and surrounding tissues compromising quality of life for many individuals. They affect between 5-10% of the U.S. population with an annual incidence rate that is greater in females compared to males (~2:1) and often lack correlation between overt signs of injury and pain intensity ratings. TMJDs may also present with other systemic and comorbid medical conditions and overlapping pain conditions (e.g., fibromyalgia, back pain, headache, irritable bowel syndrome). As such, these disorders have long confounded medical and dental health care providers often resulting in misdiagnosis and delayed or ineffective treatment. The complexity of TMJDs was the subject of a National Academies of Sciences, Engineering, and Medicine 2020 Consensus Study Report titled “Temporomandibular Disorders: Priorities for Research and Care” covering the breadth of findings, conclusions, and recommendations of the committee.

The absence of a firm mechanistic understanding of TMJDs has precluded stratification of patients into clinically meaningful and mechanistically based subgroups and identification of clear etiological targets for development of effective evidence-based treatments. Additionally, findings from immune-nervous system interactions and genetic risk factors for TMJD, though indicative of critical roles in management of chronic pain, pain perception, affective responses, and inflammation, remain inconclusive. Emerging clinical data suggest that patients with chronic pain have different phenotypic circulating T cell profiles compared to controls, with females potentially activating more adaptive immune cells because of a higher number of resident circulating CD4+ and CD8+ T cells than males. Congruent with this, circulating proinflammatory cytokines are increased in TMJD patients with widespread pain differed in allelic frequency of single nucleotide polymorphisms (SNPs) that mapped to a T-cell receptor pathway. Although recent studies have made some progress through the identification of three distinct patient subgroups across an array of biopsychosocial risk factors, further research correlating stratification approaches and TMJD clinical heterogeneity is needed.

There have been few examinations of target tissues (e.g., synovial fluid, muscle, skin) or blood from human subjects with TMJDs that use large-scale, non-targeted approaches, in the areas of genomics, epigenetics, transcriptomics, immune profiling, metabolomics, proteomics and immunophenotyping. While mechanistic understanding of TMJDs has been advanced through human and animal studies, progress has been hampered by limited emphasis on changes in affected human target tissues and few integrated analyses combining findings in multiple cells and tissues. Recent technological advances in microfluidics, machine learning, and gene expression profiling have led to advances in single cell biology—such as single-cell RNA sequencing (scRNA-seq), single-cell mass spectrometry (CyTOF), transposase-accessible chromatin sequencing (ATAC-seq), and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq)—that allow multi-dimensional profiling of individual cells from complex tissues and organs. For example, single-cell gene expression profiling now allows for identification of gene expression signatures of small populations of cells within a tissue, that may yield unique insights into mechanisms driving disease pathogenesis and outcomes. Application of such technological advances to TMJDs is critical to enable deconstruction of key events in cells and tissues related to disease, disease severity, resolution, and response to therapy.

Research Objectives

Applications to this FOA must develop protocols and methods, and assay human specimens in a clinical laboratory such that the information obtained can be used as molecular disease classifiers or diagnostic/prognostic/predictive biomarkers and/or therapeutic targets for TMJD. The project must focus on cells whose assayed marker or classifier is likely to be used in diagnosis or prevention and treatment of one or more specific TMJD disease states. Applicants should use technologies already in use or soon to be approved for use in clinical laboratories.

Research objectives for these feasibility studies are expected to contribute to long term goals that include, but are not limited to:

  • Customization of cell-isolation, sample preparation and data generation methods -to the TMJ and surrounding tissues- that produce Findable, Accessible, Interoperable, and Reusable (FAIR)-friendly data with improved sensitivity, spatiotemporal resolution, multiplexing capability and scalability.
  • Generation of an integrated data set of changes at the molecular level obtained by extensive profiling of gene expression and signaling in immune and tissue-resident cells.
  • Characterization of modules and pathways, and how they can be used to understand differences across TMJD disease states and between chronic TMJDs and chronic TMJD that present with other chronic overlapping pain conditions, including understanding sex differences.
  • Chart rewiring of cell-cell interactions by mapping receptor-ligand pairs onto cell subsets to construct putative cell-cell interaction networks across disease states.
  • Identification of changes in circulating cells in blood that correlate with activation of specific pathways in target tissues that can be used to improve patient stratification, serve as surrogate biomarkers for diagnostic or treatment decisions, or improve therapeutic targeting.
  • Application of machine learning and computational modeling for a systematic approach to integration of datasets into pathways.

Research projects that involve vertebrate animals or technology development are not responsive to this FOA.

Investigators responding to this FOA must address plans for both UH2 and UH3 phases in two separate and clearly defined stages in the single application package.

Planning and Feasibility Phase (UH2)

The UH2 award will provide one year of support for planning activities, such as finalizing the protocol and preparing other documents or required data sources to implement the study. Applications must demonstrate feasibility of recruiting subjects and the ability to collect sufficient high quality TMJD samples from humans to provide adequate power for analysis to meet the goals of this FOA. TMJD samples include but are not limited to TMJ synovial fluid, muscle, skin, bone, cartilage, connective tissue, and blood. Any specimens obtained from cadavers must show evidence of sufficiently high quality or signal compared to that from living subjects. Regardless of source, well calibrated and documented medical and dental histories need to be included, where possible, that encompass but are not limited to type and onset of symptoms, current and past treatments, diet, stress, trauma, and other illnesses. During the UH2 planning phase, limited activities such as working out logistics for data collection are allowed for determining parameters for standardization of protocols.

Examples of activities supported during the UH2 phase include, but are not limited to, developing the following:

  • A final clinical protocol, prepared using the standard NIDCR observational protocol template (see NIDCR Toolkit for Clinical Researchers), that is ready for submission to the central IRB;
  • Successful preparation of the manual of procedures, quality management plan, and data management plan, as applicable;
  • Finalization of all documents necessary to implement the full study (e.g., case report forms, etc.);
  • Consent form(s);
  • A recruitment/enrollment and retention plan for the clinical study;
  • Demonstrating feasibility of recruiting the target number of human subjects (e.g., surveys);
  • Establishing best methods of biopsy/sample collection such as of synovial tissues;
  • Establishing specific plans to collect appropriate and scientifically justified tissue samples from controls;
  • Demonstrating the capability to obtain useful data from the volumes and quantities of target tissue that will be collected;
  • Establishing a data management system across all sites for data sharing;
  • Developing new or optimization of existing technical protocols for analytical assays to be used in the UH3 phase;
  • Validating analytical and clinical assays in the application team's clinical laboratory;
  • Obtainment, quality review, and assurance of data harmonization and interoperability; and
  • A final statistical analysis plan.

Implementation Phase (UH3)

The UH3 award will provide up to two years of support to conduct the feasibility study in accordance with activities planned in the UH2 phase and is contingent upon successful completion of the UH2 milestones. The goal of the UH3 phase is to demonstrate the feasibility of one or more single cell analytics of human blood, fluid, and tissue samples in one or more TMJD that enable identification of classifiers, biomarkers, and/or targets. Singe cell analytics comprise but are not limited to the following: scRNA-seq, CyTOF, ATAC-seq, and CITE-seq. An early transition to the UH3 phase is allowed if UH2 milestones are met; no additional funds will be provided beyond what was in the original UH3 budget request.

UH3 implementation phase may include the following activities, expressed as UH3 milestones:

  • Activating sites for recruitment and enrollment of human subjects;
  • Identifying cell populations and their effector pathways in TMJD target tissues;
  • Profiling of genomics, transcriptomics, metabolomics, proteomics in target cells;
  • Immune profiling and immunophenotyping;
  • Identifying molecular disease classifiers allowing for patient stratification;
  • Identifying diagnostic, prognostic, or predictive biomarkers;
  • Delineating cellular and molecular mechanisms that mediate TMJD resolution and homeostasis;
  • Identifying candidate therapeutic targets;
  • Implementing computational and machine learning methods for data mining; and
  • Integrating analysis of findings in multiple cells and tissues.

UH2/UH3 Transition

All projects must be driven by well-defined milestones for the UH2 planning phase and milestones for the UH3 implementation phase. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. At the completion of the UH2 planning phase, the applicant will be required to submit a detailed transition application, which will undergo an administrative review by NIDCR staff to determine whether the project will be awarded for the UH3 implementation 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.

Prospective applicants should note that initial funding of the UH2/UH3 cooperative agreement does not guarantee funding of the UH3 implementation phase. Transition to the UH3 phase is dependent on having successfully met the UH2 planning milestones, NIDCR program priorities, and availability of funds. The quality of the study-related documents and plans, and demonstration of feasibility of recruitment of human subjects are given key consideration in NIDCR's review for transition to the UH3 implementation phase.

A timeline must be included for both phases outlining completion of planning activities, expected activation and completion of enrollment, start of sample analysis and data collection, and completion of analysis. Milestones should be mapped onto this timeline.

Additional Information:

A clinical laboratory is a site that tests human specimens for health assessment or to diagnose, prevent, or treat disease and must follow regulations outlined in the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Assays to test postulates or mechanisms should conform to Good Laboratory Practice (GLP) or ISO 17025 standards in order to assure that the data generated by the assay are of sufficient quality as to be useful in clinical trials and to justify sample collection. Multiple clinical sites and CLIA-certified laboratories are expected although not required.

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 implementation phase studies. It is recommended that applicants use the NIDCR Toolkit for Clinical Researchers for development of the clinical study documents. Implementation of the Clinical Terms of Award ensures that the conduct of the clinical study meets widely-accepted standards for ethical and rigorous research. The clinical study must meet all applicable NIH, and Office of Human Research Protections (OHRP) policy requirements. 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.

Adherence to common data elements (CDE) is expected to enhance data sharing. See Section IV.7 on Other Submission Requirements and Information.

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

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?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIDCR intends to commit $500,000 direct costs in FY 2022 to fund 1-2 UH2 awards.

Award Budget

Application budgets are limited to less than $250,000 in direct costs for the UH2 phase; Application budgets for the UH3 phase are limited to less than $750,000 in direct costs and need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 3 years with one year for the UH2 and up to two 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. The application must contain a Milestone Plan, according to the instructions below and must be uploaded as a separate pdf file. Applications without this Milestone Attachment will be considered noncompliant and will not undergo peer review.

1.Milestone Plan

The filename "Milestone Plan" should be used to name this attachment. The Milestone Plan must clearly describe objective and measurable milestones that will be reached at the end of the UH2 Planning and Feasibility phase, as well as annually 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 UH2 phase award. Future support of a study funded under this FOA is contingent upon achievement of milestones.

Milestones that may be completed during the UH2 phase include, but are not limited to:

  • A final clinical protocol, prepared using the standard NIDCR observational protocol template (see NIDCR Toolkit for Clinical Researchers), that is ready for submission to the central IRB;
  • Successful preparation of the manual of procedures, quality management plan, and data management plan, as applicable;
  • Finalization of all documents necessary to implement the full study (e.g., case report forms, etc.);
  • Consent form(s);
  • A recruitment/enrollment and retention plan for the clinical study;
  • Demonstrating feasibility of recruiting the target number of human subjects;
  • Establishing best methods of biopsy/sample collection such as of synovial tissues;
  • Establishing specific plans to collect appropriate and scientifically justified tissue samples from controls;
  • Demonstrating the capability to obtain useful data from the volumes and quantities of target tissue that will be collected;
  • Establishing a data management system across all sites for data sharing;
  • Developing new or optimization of existing technical protocols for analytical assays to be used in the UH3 phase;
  • Validating analytical and clinical assays in the application team's clinical laboratory;
  • Obtainment, quality review, and assurance of data harmonization and interoperability; and
  • A final statistical analysis plan.

Milestones to be completed during the UH3 phase may include:

  • Activating sites for recruitment and enrollment of human subjects;
  • Identifying cell populations and their effector pathways in TMJD target tissues;
  • Profiling of genomics, transcriptomics, metabolomics, proteomics in target cells;
  • Immune profiling and immunophenotyping;
  • Identifying molecular disease classifiers allowing for patient stratification;
  • Identifying diagnostic, prognostic, or predictive biomarkers;
  • Delineating cellular and molecular mechanisms that mediate TMJD resolution and homeostasis;
  • Identifying candidate therapeutic targets;
  • Implementing computational and machine learning methods for data mining; and
  • Integrating analysis of findings in multiple cells and tissues.
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:

Specific Aims:

Present separate specific aims to be accomplished for the UH2 and UH3 phases, clearly labeling each as UH2 Planning and Feasibility Specific Aims and UH3 Implementation Specific Aims.

Research Strategy:

Approach:

The Approach section should have a clear demarcation of the UH2 and UH3 portions of the application.

For the UH2 phase:

  • Describe the study development activities planned for the UH2 phase. Be sure to include description of plans for protocol development (both clinical and technical), standard operating procedures, recruitment, and processes associated with the analytical work planned in the UH3 phase.
  • Provide a 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 research objectives. Include a statistical analysis plan.
  • Address the feasibility of recruiting participants who are eligible for the proposed study. Include outreach activities and pre-study assessments of the ability of participating clinical sites to recruit the proposed target number of participants. 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. Include alternative strategies (e.g., adding/dropping clinical sites) should enrollment not meet specified metrics.
  • Address how sites will handle and process specimens prior to their analysis, as well as management of data collected to facilitate data sharing. Processes should detail the ability to coordinate activities across all sites involved in the study for standardization of collection and data management.

For the UH3 phase:

  • Describe activities for launching the study and how the plans developed in the UH2 planning phase will be implemented.
  • Provide an overview of the proposed study design including all assays and single cell analytics for the chosen TMJD specimens collected. Include the scientific rationale for performing the selected profiling and identification experiments, and how the analysis and/or data mining methods contribute to the goals of the FOA in identifying disease classifiers, biomarkers, or therapeutic targets in TMJD.

Timeline:

A timeline must be included for both phases outlining completion of planning activities, expected activation and completion of enrollment, start of sample analysis and data collection, and completion of analysis. Milestones should be mapped onto this timeline.

Environment:

  • Describe the facilities that will be performing the single cell analytics and indicate how they meet CLIA certification or GLP standards, whichever is applicable. Include how the facilities and collection sites interact or are integrated with each other and their infrastructure allowing for seamless transfer of specimens and data. If more than one facility or collection site is involved, describe policies for standardization and how technical variation is controlled or minimized.

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 a Resource Sharing Plan.
  • Describe how data will adhere to FAIR principles, meaning that it should be Findable, Accessible, Interoperable, and Reusable (FAIR). To be Findable, data must have unique identifiers, effectively labeling it within searchable resources. To be Accessible, data must be easily retrievable via open systems and effective and secure authentication and authorization procedures. To be Interoperable, data should “use and speak the same language” via use of standardized vocabularies. To be Reusable, data must be adequately described to a new user, have clear information about data-usage licenses, and have a traceable “owner’s manual,” or provenance. These principles are also outlined in the NIH Strategic Plan for Data Science.
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.

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.

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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. Research projects that involve vertebrate animals or technology development are not responsive to this FOA.

In order to expedite review, applicants are requested to notify the NIDCR Referral Office by email at yasaman.shirazi@nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (https://cde.nlm.nih.gov/home) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

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.

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?

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?

Does the study team provide evidence demonstrating their ability to coordinate activities across all sites?

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?

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?

 

Does the UH2 section describe in sufficient detail the planning activities for both the UH2 and UH3 phases? Does the description cover all aspects beginning from protocol development to data analysis? Does the study team demonstrate convincingly they have the capability to recruit the target number of study participants? Are alternative strategies included for ensuring enrollment target is met? Are there appropriate descriptions and justifications of the study population and disease condition supported by statistical analysis? Is the description of handling specimen and data comprehensive enough to ensure standardization of collection and data management across all sites?

Does the UH3 section sufficiently describe how plans developed in the UH2 phase will be implemented? Is adequate rationale provided for choice of study design, single cell analytics, and data analysis/mining methods that contribute to the goals of the project?

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?

 

Do descriptions of facilities performing single cell analysis clearly indicate their capability at conforming to quality laboratory standards and FAIR data? If more than one facility and collection site are involved, are there adequate interaction and integration and do plans impart confidence that technical variation can be controlled and minimized?

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.

Milestone Plan

Do the milestones described in the attachment serve as a measurable set of events that can easily be determined as having been met? Are the listed milestones complete and reflective of the work proposed in the UH2 phase, and annually for the UH3 phase?

Study Timeline

Is the study timeline described in detail, taking into account start-up activities and the anticipated rate of enrollment? Is the projected timeline feasible and well justified?

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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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.

Recipients 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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 the 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, 2 CFR 200 and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipient 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 recipient for the project as a whole, although specific tasks and activities may be shared among the recipient and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

  • Providing scientific leadership for all aspects of the study, including planning, any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The PD(s)/PI(s) agrees to accept close coordination, cooperation, and participation of NIDCR staff in those aspects of scientific and technical management of the study as stated in these terms and conditions;
  • Adhering to the NIDCR Clinical Terms of Award and the NIDCR Policy on Data and Safety Monitoring requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study;
  • Upon implementation of the study, following the procedures required by the protocol regarding study conduct and monitoring, participant management, data collection, and quality control;
  • Retaining custody of and having primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies;
  • Making all study materials, procedure manuals, and final datasets available in the public domain, managed by the recipient institution. Recipients 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 UH2 and UH3 milestones;
  • 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 personnel to monitor study development and implementation progress, adherence to the study protocol, conduct of the study, and recruitment 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, recipients 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, 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 recipient 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 award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

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 recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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)

Jason Wan, PHD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-9898
Email: jasonwan@mail.nih.gov

Elizabeth Anne Barr
Office Of Research On Women's Health (ORWH)
Phone: 301-402-7895
E-mail: elizabeth.barr@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 2 CFR 200, 42 CFR Part 52 and 45 CFR Part 75.


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