Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
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)
None
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.
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.
Not Applicable
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.
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:
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:
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:
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.
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.
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.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
NIDCR intends to commit $500,000 direct costs in FY 2022 to fund 1-2 UH2 awards.
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.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign 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.
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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:
The letter of intent should be sent to:
Yasaman Shirazi, PHD
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
Milestones to be completed during the UH3 phase may include:
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
For the UH3 phase:
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:
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:
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.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
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
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.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
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.
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.
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.
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).
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.
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?
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?
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?
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?
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?
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
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.
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
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
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.
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.
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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
An NIDCR Project Scientist will be assigned. The NIDCR Project Scientist will:
An NIDCR Program Official will be assigned. The NIDCR Program Official will:
An NIDCR Medical Officer will monitor the studies and serve as the Medical Monitor.
The NIDCR reserves the right to terminate or curtail a study or any portion of a study in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, 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:
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.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: 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
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
Yasaman Shirazi, PHD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email:yasaman.shirazi@nih.gov
Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email:rutbergd@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR 200, 42 CFR Part 52 and 45 CFR Part 75.