Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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.
   
   



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The National Institute of Dental and Craniofacial Research (NIDCR), along with the Organizations, Institutes, Centers, and Offices (ICOs) listed in Part I, invites applications in response to this Notice of Funding Opportunity (NOFO) for the Temporomandibular Disorder (TMD) Collaborative for Improving Patient-Centered Translational Research (TMD IMPACT). The purpose of TMD IMPACT is to establish a national, interdisciplinary, patient-centered research collaborative that will advance TMD basic and clinical research, research training, and translation of findings to evidence-based treatments and improved clinical care. The TMD IMPACT Collaborative will be composed of one or more Center(s) designed to coordinate and leverage shared resources, expertise, and collaboration across multiple topic areas and interdisciplinary teams. Collectively, the Collaborative will be a coordinated, cohesive, multi-level and strategic approach to advance the science of TMD research and substantively improve TMD patient care, beyond the capabilities of single projects and studies. While this effort continues at a larger scale than RFA-DE-23-014 planning grants for TMD-IMPACT, this NOFO is open to all interested and eligible teams with appropriate expertise and is not limited to those who were funded under the planning grant RFA. Stakeholder engagement must include patients and/or their advocacy groups (PAGs) who will directly engage with the Center and its projects.

The key objectives of the TMD IMPACT Collaborative are to: 1) support robust and rigorous TMD basic research that leads to clinically relevant insights and mechanistic understanding; 2) develop translational programs and support clinical research to improve diagnosis, prevention, and treatment of the various TMDs to ultimately improve standard of care; 3) strengthen population-based research on the public health burden and costs of TMDs to improve prevention and management of TMDs, and health services and implementation research to improve quality and access to care; and 4) train the future TMD biomedical workforce that represents a diverse pool of individuals from all background career stages, and appropriate scientific disciplines consistent with applicable law. 

Background

Temporomandibular Disorders (TMDs) are a set of more than 30 heterogeneous health disorders associated with the temporomandibular joint (TMJ), muscles of mastication, and surrounding tissues. The TMJ’s skeletal and connective tissues originate from the neural crest during early development, rather than from the mesoderm, indicating different genetic drivers and pathways than in other joints. TMDs are pain conditions with multifactorial components that range from acute to chronic, and from mild to severe, 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. TMDs may present with other systemic and comorbid medical conditions. There is chronic overlapping or frequent co-occurrence between TMD and chronic pain conditions (COPCs) such as fibromyalgia, back pain, headache, and irritable bowel syndrome, indicating changes in central processes. The heterogeneous etiologies and varied clinical presentations of TMDs make accurate, clinically relevant, and mechanistically based phenotyping difficult.

Studies indicate that TMDs are multifactorial conditions influenced by genetics, sex and gender, environmental and psychological factors; however, significant gaps remain in our understanding of peripheral and central adaptation mechanisms, psychosocial influences, sex and gender differences, and the epigenetics that drive chronic pain development versus resolution of TMD pain. While our mechanistic understanding of TMDs has been advanced through human and animal studies, progress has been hampered by limited clinically relevant animal models, lack of clear ontology and data standards, and limited machine learning approaches and integrated analyses combining findings in multiple cells and tissues. The absence of a firm mechanistic understanding of some TMDs has precluded stratification of patients into clinically meaningful and mechanistically based subgroups and hampered identification and validation of clear etiological targets for development of effective evidence-based treatments or their clinical endpoints.

TMDs have long confounded medical and dental health care providers, often resulting in misdiagnosis, diminished quality of life, and delayed and often ineffective treatment. There is a clear need to accelerate research and treatment breakthroughs on TMDs, as well as to educate and train investigators, clinicians, and dentists who are at the forefront of TMD research and/or patient care. The complexity of this set of disorders calls for a coordinated, integrated, interdisciplinary and multi-level approach to address TMD comprehensively using a whole-person perspective. Whole person health involves looking at the whole person—not just separate organs or body systems—and considering multiple factors that promote either health or disease. Instead of just treating a specific disease, whole person health focuses on restoring health, promoting resilience, and preventing diseases across a lifespan.

The research framework of the TMD IMPACT Collaborative is interdisciplinary, addressing TMD-related research questions that single independent research projects cannot tackle and covering a broad swath of the translational spectrum as described below under research projects. 

Organization of the TMD IMPACT Collaborative

The objectives of the TMD IMPACT will be carried out within a research infrastructure to be established through this NOFO, which will support TMD IMPACT Centers, and future NOFOs which will together form the TMD IMPACT Collaborative. The Collaborative is defined as the consortium of investigators and institutions funded under all related NOFOs. It is also reasonable for projects and strategies to align with existing federally funded efforts to establish a national TMD/TMJ patient registry and Coordinated Registry Network (CRN). 

TMD IMPACT Collaborative Elements

Each TMD IMPACT Center application (U54) must include the following elements:

1. Administrative Core (AC)
2. Bioinformatics/data science Core (BDSC)
3. Outreach, Training, and Education Core (OTEC)
4. One to three Research Projects

Administrative Core (AC)

The Administrative Core of each TMD IMPACT U54 will be responsible for the following activities:

• Administrative Support: The Administrative Core is responsible for the overall management of day-to-day program activities, providing support for communications, and meeting necessary requirements and regulations by Federal Agencies and all the collaborating institutions. Clear policies and procedures should be established for the Center that dovetail with those of the Collaborative. The Administrative Core will facilitate the process of monitoring the progress of program milestones that will be negotiated at the time of award. All TMD IMPACT-related meetings and calls will be managed by the Administrative Core along with coordination of the activities of the TMD IMPACT Executive Committee. The Administrative Core will also serve as the primary point for coordinating collaborations and BDSC-related activities.
• Management of the TMD IMPACT Center’s Agreements and Regulatory and Clinical Documentation: The Administrative Core will coordinate and manage all regulatory and clinical study documents in collaboration with the NIH. The Administrative Core will establish data sharing and data use agreements within the Collaborative, for all clinical sites, and among the primary recipient institutions.
• Coordination of Activities within the TMD IMPACT Collaborative: The Administrative Core will work collaboratively across all Cores (AC, BDSC, and OTEC) to coordinate and support the activities of the Center within the Collaborative’s research framework. They will also collaborate with the BDSC to establish and promulgate coordinated TMD IMPACT data management and data sharing standards and policies.
• Management and Sharing of Data and Biospecimens: The Administrative Core will coordinate BDSC-related activities and biospecimen sharing, storage and tracking information across all sites within the Collaborative and externally with appropriate agreements. This Core will also be responsible for promulgating data and findings to the public and is expected to work closely with the OTEC. The Administrative Core will also coordinate with existing specimen and data repositories to develop a data ecosystem for the Collaborative, establishing standards, data standards, data dictionaries, and other metadata.

Bioinformatics and Data Science Core (BDSC)

The Bioinformatics and Data Science Core will conduct research in the form of secondary data analyses of existing national population health data and data generated by the Center research projects, and employ AI/ML/DL approaches to integrate multi-modal data to identify potential therapeutic targets, prognostic models, molecular phenotyping and patient stratification, develop ontology and metadata, establish common data elements (CDEs), and other critical applications.

The BDSC may engage collaborators across Centers to conduct the research. Methodologies and findings are expected to follow the resource sharing plan and Data Management and Sharing plan (DMSP). Any secondary data generated from these analyses should also follow the principles of Findability, Accessibility, Interoperability, and Reusability (FAIR) data practices across projects and Cores.   

Projects conducting research with human participants must include validated and structured questionnaires, for example the questionnaires responsive to the NIH Helping to End Addiction Long Term (HEAL) Common Data Elements for pain measures. Additionally, all data collected and generated within the BDSC are expected to integrate with the research projects, and reciprocally feed the other Cores, particularly the OTEC which can be disseminated as clinical practice guidelines.

Outreach, Training, and Education Core (OTEC)

The Outreach, Training, and Education Core of each TMD IMPACT U54 will be responsible for the following activities:

• Outreach
  • Engagement of scientific, medical, dental, patient, and other stakeholder groups for the dissemination of Information: This core will be expected to engage a wide group of stakeholders in the dissemination of information related to research outcomes, best practices, and other publications, workshop proceedings, and products directly resulting from the Collaborative, to serve as a national resource for information.  Engagement can be in the form of public workshops and/or symposia at national and international conferences. Public workshops for dissemination should also be used to obtain input and feedback on steps and/or standards that have been or will be developed. Holding widely advertised public workshops no less than once yearly is required for each Center and/or across the Collaborative.
  • Coordination of Patient Advocacy Groups Participation: Patients and their advocacy groups (PAGs) provide a unique and grounded source of primary needs and input to the scientific and clinical realms and therefore must be present and actively engaged in this effort. Active engagement can be achieved by providing PAGs a voice such as seats on committees, presentation/panel slots at workshops and conferences, and embedding PAGs as dedicated channels to projects and studies for sharing input and/or voicing concerns. Ultimately, PAGs will be both a target audience as well as collaborators, and are encouraged to aid in the dissemination of information and educational materials.
• Training/Education
  • Training the future TMD biomedical workforce that represents a diverse pool of individuals from all background career stages, and appropriate scientific disciplines consistent with applicable law and offer research education for medical and dental health care providers. Providing knowledge, skills, and research experiences must be a core function as it will ensure a broad, competent pool of long-standing early career independent investigators who will form the future of the community. Mentorship, the implementation of individual career development plans and didactic programs should be established by the Core. Research education of current clinicians, dentists and health providers on the latest advances in research and treatments for TMDs is also needed to facilitate translation of research and evidence-based approaches to patient care. Integration of diverse perspectives, especially from patients, is expected in curriculum development, whether for research education, research experiences, or research training.
  • Development of curricula and educational resources: In order to educate and train researchers and clinicians, a suite of curricula needs to be developed that is focused on teaching critical research knowledge and skills that may not have been part of established courses in academic and professional schools. Coursework that incorporates new scientific findings, strategies of diagnosis and treatment, among other knowledge are expected to be developed that will augment existing knowledge. Educational resources for the community to clinical specialists will also be expected to be developed. These resources are expected to cover the range of print to electronic media that is accessible to different ages and comprehensive abilities of individuals who may be seeking such information. A curated, central resource library that is searchable and interactive is central to these educational and dissemination efforts.

Research Project(s)

Each Center is expected to conduct one to three research projects that may span the range of the translational spectrum, from mechanistic pre-clinical research up to clinical research studies and NIH-defined Clinical Trials. Each project is expected to be interdisciplinary and impactful to the field, addressing a challenging research question. The proposed research projects within each Center should be coordinated and synergistic to address TMD comprehensively using a whole-person perspective that includes a set of goals that are not achievable by smaller individual projects. A project significantly large in size and duration, such as a longitudinal cohort trial, can be considered as a single project.

Specific Areas of Research Projects include, but are not limited to, those listed below.  It is not expected that each Center will include all bullets.

• Prospective cohort study/Patient Outcomes that follow the course of the disease collecting appropriate and well justified clinical endpoints and/or measures including phenotyping or identifying and validating etiological targets that allow for stratification of patients into clinically meaningful and mechanistically based subgroups.
• Mechanistic studies on molecular pathogenesis, disease progression, pain chronification, or resilience that correlate with stratification approaches and TMD clinical heterogeneity including sex and gender differences that predisposes females more than males to develop a TMD; as well as mechanisms that sustain or promote endogenous resolution of chronic TMD pain and/or prevent the transition from acute to chronic pain.
• Epidemiology, health services research or human behavioral/upstream determinants of health that consider all aspects of lifestyles, biopsychosocial, and socioeconomic factors that could include data from a national TMD patient registry/Coordinated Registry Network (CRN) and healthcare organizations including Centers for Medicare & Medicaid Services (CMS).
• Systems biology, whole-organ, and whole-person approaches that include biopsychosocial mechanisms and consider mental health comorbidities, chronic stress, affective influences on pain, and chronic overlapping pain conditions (e.g., headache, mixed musculoskeletal or myofascial pain).
• Biomechanical, tissue engineering, biomaterial, and regeneration studies.
• Development of new minimally invasive treatments and therapies (e.g., thermotherapies, local chemical injections, and force-based manipulations such as dry needling) and/or strengthening the mechanistic understanding of current pharmacological and non-pharmacological interventions; and symptom management using biobehavioral approaches.
• Adaptation and utilization of existing tools/technologies that are used in other applications, or development of new tools, devices, and technologies that can encompass diagnostic or prognostic modalities, through instrumentation, imaging, or methodologies to facilitate non-invasive assessment and surgical exposure to the TMJ and the unique orofacial physiology; these approaches can also be used towards establishment of potential therapeutic modalities.
• Artificial Intelligence/Machine Learning/Deep Learning (AI/ML/DL) and computational methods (e.g., statistical modeling, natural language models, etc.) to leverage large datasets for purposes such as developing knowledge maps, distinguishing disease subtypes, developing individualized clinical decision support, predicting patient responses, informing reverse-translational approaches, or integrating data from various animal models.
• If the Research Project is a Clinical Trial (e.g., efficacy trials, Basic experimental studies involving humans (BESH), pragmatic trials, and comparative effectiveness trials), specific areas of interest include but are not limited to:
  • Adaptive study-design trials that can significantly increase value and information gathered by incorporating modifications into ongoing trials.
  • Pragmatic trials conducted within real-world health care delivery settings including registries.
  • Implementation studies that execute properly planned and prepared protocols and procedures developed with stakeholder input.

Milestones

TMD IMPACT U54 milestones are expected to inform annual evaluations of progress of the Collaborative and must be included as part of the application. Prior to funding an application, the NIH Program Officer (PO) will contact the applicant to discuss the proposed milestones and any concerns raised by the review panel or program staff. A final set of NIH-approved milestones for each year of the project period will be agreed upon prior to award.

TMD IMPACT Collaborative Governance

The awards funded under this NOFO will be cooperative agreements (see Section VI.2. Cooperative Agreement Terms and Conditions of Award). The Collaborative will consist of all the funded TMD IMPACT Centers, recipients of awards from future TMD IMPACT NOSIs and NOFOs, and NIH program representatives. Governance of the TMD IMPACT Collaborative will consist of the following committees:

1. TMD IMPACT Collaborative Steering Committee (SC) - The SC will identify scientific and policy issues that need to be addressed at the Collaborative level and review and approve all Collaborative-wide policies. It will also ensure dissemination of program data, education and outreach and other materials to the wider scientific community. The SC may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific Collaborative functions as needed. The SC is composed of:

• NIH PO(s)/Subject Matter Experts (SMEs) from participating ICOs (where appropriate)
• The Centers PI(s) (including research project PIs and Core PIs)
• Patient and/or Patient Advocate Group
• Working Group Chairs

2. TMD IMPACT Collaborative Executive Committee (EC) - The EC will meet on a monthly basis to hold strategic discussions regarding the Collaborative functioning and will make executive decisions related to activities. The EC will screen any potential cross-program research projects, vote, and make recommendations to the Collaborative SC. In addition, the EC will discuss any issues in need of consensus or resolution and will identify solutions to be discussed with the SC. The EC is composed of:

• NIH PO(s) (non-voting members)
• Center Contact PI(s)
• SC Chairs
• One Patient Advocate Group Representative

3. External Consultants (XC) - The External consultants are experts who will individually advise NIH Program staff on the progress of the Collaborative, on the contributions of individual projects and/or project collaborations within the Collaborative, and on the progress and effectiveness of the consortium as a whole. The XC are expected meet in-person or electronically at least once a year with NIH, beginning in the first or second year of the award after major activities have begun. External consultants are also expected to attend the annual Collaborative public workshop.

All recipients of a TMD IMPACT award and their teams are members of the Collaborative. Each Center will be expected to actively participate in Collaborative activities, including meetings of the Steering committee, Collaborative annual face to face meetings, and various relevant working groups.

Each Center must be willing to work towards being a member of the Collaborative by supporting common data standards; encouraging the use of CDEs; following FAIR principles across sites; committing to community engagement; and agreeing to share data and other resources to this network, the broader scientific research community, and the general public.

IC Specific Interests

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) supports research on the development and optimization of nonpharmacological interventions using complementary and integrative health approaches to treat acute or chronic pain conditions, including temporomandibular disorders. Complementary health approaches include a broad range of practices and interventions that are not typically part of conventional medical care and can be classified by their primary therapeutic input, including nutritional (e.g., special diets, dietary supplements, herbs, probiotics, and microbial-based therapies), psychological (e.g., meditation, hypnosis, music-based interventions, relaxation therapies), physical (e.g., acupuncture, massage, chiropractic manipulation, other force-based manipulations, or devices related to these approaches), or a combination of psychological and physical (e.g., yoga, tai chi, dance therapies, or some forms of art therapies, such as music-based interventions) input.

National Institute of Neurological Disorders and Stroke (NINDS)

Pain-related research that aligns with NINDS research priorities such as studies on pain sensitization, chronification, headaches, and migraines, are of particular interest to NINDS. NINDS also supports pain research that explores the neurological origins, including studies on the physiology of non-entrapment nerve injuries, genetic nerve disorders, and neural dysfunctions or etiologies. NINDS is also interested in research focused on the central nervous system's role in pain control.

Applications Not Responsive to this NOFO

The following types of research projects are not responsive to this NOFO. Applications proposing such projects will be considered non-responsive, will be withdrawn from review, and not considered for funding.

• Applications without the involvement of patients and/or their advocacy groups
• Research projects focused on the creation of new, centralized biorepositories or patient registries
• Applications without a dissemination Plan that expressly shares Collaborative resources, products, and opportunities with the field at large.
• Applications that do not propose an annual public workshop or symposium

Pre-Application Consultation with Scientific/Research Staff

Consultation with the NIH staff at least 8 weeks prior to the application due date is strongly encouraged for all applicants considering submitting an application to discuss the alignment of their proposed work with the goals of this NOFO and the TMD IMPACT Collaborative. IC staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this NOFO. During the pre-application consultation phase, if the proposed TMD IMPACT Center does not meet an ICO's programmatic priorities, applicants will be strongly encouraged to consider other funding opportunities.

Pre-application Information Session

A technical assistance teleconference will be held for potential applicants. Time, date, and dial-in information for the call will be announced in an NIH Guide Notice.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

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

Non-domestic (non-U.S.) Entities (Foreign Organization) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. 

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions of Terms.

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 per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - 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 How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Bioinformatics/Data science Core: required; maximum of 1
• Outreach, Training, and Education Core; required, maximum of 1 
• Research Projects; required; minimum of 1, maximum of 3

Overall Component

When preparing the application, use Component Type ‘Overall’.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

Travel Funds: The budget should include sufficient funds to support travel for PD(s)/PI(s) and pertinent members of the Center to attend annual Collaborative meetings and/or workshops.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims:  Describe the overall goals of the TMD IMPACT Center for the performance period of the award. Describe the research objectives of the Center to establish a national, interdisciplinary, patient-centered research collaborative that will advance TMD basic and clinical research, research training, and translation to evidence-based treatments and improved clinical care.

Research Strategy: This section should describe the major objectives of the Center, its goals, background information, the overall importance of the research, and significance of the Center to the Collaborative.

• Describe the rationale for the overall proposed Center.
• Briefly describe the research projects and cores and provide a figure of the organizational structure of the Center.
• Clearly state the unmet research/clinical needs these projects address, and how the Center will accelerate progress toward TMD basic and clinical research, research training, and translation to evidence-based treatments and improved clinical care.
• Describe how the projects and cores contribute to the overall goals and objectives of the Collaborative in advancing understanding TMD.
• Describe the PD(s)/PI(s) expertise in managing large multi-component clinical research programs.
• For multi-PD/PI applications, describe their complementary and integrated expertise, and comment on their leadership approach, governance, and organizational structure.
• Indicate prior collaborative relationships among proposed senior key personnel at the various sites and across the Collaborative.
• Describe the leaders and collective teams for each core and how their skills complement each other to contribute to the overall team.
• Describe the nature of the ongoing relationships with patient advocacy group(s) and the approach of patient or stakeholder participation across the planned objectives. Describe how patient and stakeholder experiences, perspectives, needs, and priorities will be meaningfully incorporated as partners into decisions and activities of the Center.
• Describe plans for the Center to collaborate and otherwise contribute to the overall Collaborative, through participating in Collaborative-wide committees, workshops, meetings, career enhancement, collaborative efforts, or other Collaborative-wide activities and initiatives. 

Letters of Support: Applicants must provide letters from the appropriate high-ranking institutional official(s) from the lead institution and partnering institutions that:

• Commit the institution(s) to the Collaborative’s goals.
• Defines the position, authority, and reporting responsibility (on the institution's organizational chart) for the PD(s)/PI(s).
• Defines the financial and other resource support for the Center that will be provided by the applicant institution(s). There are no dollar requirements, but specific commitment is required. Some examples include financial support, adequate space, release time agreements, tenured or tenure-track positions for clinical/translational faculty, FTEs for clinical support or ancillary personnel, core consolidation, and maintenance. Specific commitments to cores and other components can be summarized in a table.

Applicants may provide letters of support specific to the cores or projects if they do not duplicate other letters of support. Please label each core- or project- specific letters of support with the component it is supporting.

Supporting letters from patient or stakeholder groups must be included.

Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

For Research Studies that include Clinical Trials:

2.5 Recruitment and Retention Plan

Describe the plan to recruit/enroll the population of interest for the clinical trial, including outreach activities and pre-study assessments of the ability of participating clinical sites to recruit the proposed target number of participants. Describe the plan and timing to meet the study’s retention targets. Include a discussion of strategies for retention of participants, including any methods to maximize flexibility for data collection (e.g., data collection independent of office visits).

2.7 Study Timeline

Applicants should provide separate project performance timelines for the planning phase and the implementation phase of grant period. The planning timeline should include the estimated time for completion of each of the planning milestones (see "Other Attachments"). The implementation timeline should include the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis. Project performance timelines may be refined and finalized in consultation with NIDCR Program Staff at the time of the planning phase award and the implementation phase award, if granted.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

Describe the study-specific plan to ensure data and safety monitoring, including:

Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of administering the study intervention(s). Include methods to monitor study intervention fidelity and systems to record, report and manage exceptions and deviations. If applicable, describe monitoring of participating facilities such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies, the appropriate reporting to relevant authorities, including but not limited to the IRB of record, Data and Safety Monitoring Board (DSMB) if one is assigned, FDA if applicable, institutional officials and the NIH.

Describe plans to ensure that validated systems and controls are in place to assure the integrity of the clinical trial data being collected; proposed methods and systems for data collection, data entry, data verification, data validation and adverse event reporting; and the process for locking the final trial dataset for analyses. Describe the data query process and query frequencies and any planned mitigation strategies in the event of noncompliance with data collection processes. Describe the methods and systems to ensure data confidentiality and subject privacy.

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

Section 4 - Protocol Synopsis

4.3 Statistical Design and Power

In addition to the information requested in the SF424 (R&R) Application Guide instructions, describe the plans for handling missing data.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

The application must contain the following two attachments (Schedule of Events, Quality Management Plan), according to the instructions below. The information provided here will be considered by reviewers and is meant to supplement, not duplicate, information provided in the Research Plan or the Study Record: PHS Human Subjects and Clinical Trials Information form. The following documents must be uploaded as separate pdf files with the names indicated below.

1. Schedule of Events. The filename "Schedule of Events" should be used to name this attachment. Applicants are encouraged to use the sample format (Appendix A) in the NIDCR Interventional (Clinical Trial) Protocol Template.

Provide a schematic, table, or text description of the protocol-specified schedule of events for an individual study participant. It should capture each study visit/assessment time point and planned activity(ies) for each time point.

For example:

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

2. Quality Management Plan. The purpose of the Quality Management Plan is to establish standard processes for all study-related activities, to assess and document adherence to all clinical trial procedures, and to ensure the quality of data collection procedures.

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the How to Apply- Application Guide must be followed.

Administrative Core (AC)

When preparing your application, use Component Type ‘Administrative Core'.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

The most commonly referenced Research Plan attachments are listed below for your convenience. NOFO–specific instructions are required for the Specific Aims and the Research Strategy in each component. NOFO-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no NOFO-specific instructions.

Specific Aims: The Administrative Core is responsible for the overall administration of the Center (including policy, procedure, and funds allocation).

Research Strategy:

• Describe plans for the organization and administrative management of the Center. The plan must include management of day-to-day activities, establishing policies and procedures that dovetail with those of the Collaborative, funds allocation, and monitoring progress of Center's program milestones.
• Describe the skills and experience of the Administrative Coordinator to assist the PD(s)/PI(s) and Administrative Core PI with the day-to-day administrative details and program coordination.
• Describe a plan for communication (meetings, conference calls etc.) and participation of all personnel. Provide details of how the activities and contribution of the collaborating investigators, institutions and patient advocacy groups will be coordinated.
• Describe how the Administrative Core will work collaboratively with the other Cores to coordinate and support efforts across the Center and the Collaborative.
• Describe plans for how the Administrative Core will facilitate the process of monitoring the progress of program milestones.
• Describe plans for coordination and management of all regulatory and clinical documents in collaboration with the NIH.
• Describe plans for how the Administrative Core will coordinate biospecimen storage, sharing, and tracking information across all sites within the Collaborative and externally with appropriate agreements.

Letters of Support:  All letters of support should be included in the Overall Component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component. 

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed.

Bioinformatics and Data Science Core (BDSC)

When preparing your application, use Component Type ‘Bioinformatics and Data Science Core

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Bioinformatics and Data Science Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Bioinformatics and Data Science Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Bioinformatics and Data Science Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Bioinformatics and Data Science Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Bioinformatics and Data Science Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Bioinformatics and Data Science Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Bioinformatics and Data Science Core)

The most commonly referenced Research Plan attachments are listed below for your convenience. NOFO–specific instructions are required for the Specific Aims and the Research Strategy in each component. NOFO-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no NOFO-specific instructions.

Specific Aims:  State the goals of the Bioinformatics and Data Science Core concisely and summarize the expected outcomes.

Research Strategy:

• Describe plans for the Bioinformatics and Data Science Core to conduct research in the form of secondary data analyses of existing national population health data and data generated by the Center research projects.
• Describe plans on how the BDSC will employ AI/ML/DL approaches to integrate multi-modal data to identify potential therapeutic targets, prognostic models, molecular phenotyping and patient stratification.
• Describe plans to develop ontology and metadata, establishment of common data elements (CDEs), and other critical applications.
• Identify the individual(s) with bioinformatic expertise involved across the Collaborative.
• For projects conducting research with human participants, describe validated and structured questionnaires, for example the questionnaires responsive to the NIH Helping to End Addiction Long Term (HEAL) Common Data Elements for pain measures.

Letters of Support:  All letters of support should be included in the Overall Component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Bioinformatics and Data Science Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed.

Outreach, Training, and Education Core (OTEC)

When preparing your application, use Component Type ‘Outreach, Training, and Education Core.’

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Outreach, Training, and Education Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Outreach, Training, and Education Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Outreach, Training, and Education Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Outreach, Training, and Education Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Outreach, Training, and Education Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Outreach, Training, and Education Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Outreach, Training, and Education Core)

The most commonly referenced Research Plan attachments are listed below for your convenience. NOFO–specific instructions are required for the Specific Aims and the Research Strategy in each component. NOFO-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no NOFO-specific instructions.

Specific Aims: State the goals of the Outreach, Training, and Education Core concisely and summarize the expected outcomes.

Research Strategy:

Dependent on the type of research training or research education program, relevant bullets may be included.

• Describe plans for the training of the next generation of interdisciplinary researchers to ensure a pipeline of early career, diverse investigators who will form the future of the community.
• Describe the plans to develop mentorship and individual career development plans of early-stage career researchers/trainees under mentors who are part of this Center.  Describe how mentors will be paired with trainees, and how often will they engage.
• Describe plans to develop curricula and educational resources focused on teaching new knowledge gained that may not have been part of established courses in professional schools. Describe how materials will be directed towards lay persons to clinical specialists and plans for dissemination.
• Describe the strengths, leadership and administrative skills, career enhancement experience, scientific expertise, and active research of the Outreach, Training, and Education Core Leader. Describe the Core Leader’s commitment and track record of training and career development of women, under-represented minorities, and people with disabilities.
• Describe the nature of the ongoing relationships with patient advocacy group(s) and the approach of patient or stakeholder participation across the planned objectives (e.g., in addressing clinical design, recruitment, and education). Describe how patient and stakeholder experiences, perspectives, needs, and priorities will be meaningfully incorporated as partners into decisions and activities of the Collaborative.

The following must be included:

• Describe plan for dissemination activities, including the role of PAGs. Engagement can be in the form of public workshops or symposia at national and international conferences. Public workshops for dissemination should also be used to obtain input and feedback on steps and/or standards that have been or will be developed. Holding widely advertised public workshops no less than once yearly is required for each Center and/or across the Collaborative.

Letters of Support:  All letters of support should be included in the Overall Component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Outreach, Training, and Education Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed.

Research Project(s)

When preparing your application, use Component Type ‘Research Project(s).’

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project(s))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project(s))

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project(s))

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Project(s))

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Project(s))

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project(s))

The most commonly referenced Research Plan attachments are listed below for your convenience. NOFO–specific instructions are required for the Specific Aims and the Research Strategy in each component. NOFO-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no NOFO-specific instructions.

Specific Aims: State the goals of the proposed Research Project(s) concisely and summarize the expected outcome(s).      

Research Strategy:

• Clearly describe the hypothesis or hypotheses to be tested for the project and explain its relevance to the Collaborative.
• Describe how the individual research project's goals will address the central objectives of the Collaborative.       
• Specify the gaps filled by each project in the Collaborative’s goal to advance the science of TMD research and substantively improve TMD patient care.
• Describe how the perspectives of patients and stakeholders will be included in the work proposed.
• Describe the source of common data elements that will be used in the study and how this will be coordinated across the Collaborative.

If a clinical research project includes an NIH-defined clinical trial:

• Describe the potential value of the study and the feasibility of successfully completing the study within the duration of the award, including the preclinical rationale.
• Provide evidence that the rigor of preclinical efficacy studies and the level of effect of the agent or treatment are both sufficient to warrant clinical testing.
• Describe how regulatory requirements will be met in a timely manner.

Letters of Support: All letters of support should be included in the Overall Component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Project)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed.

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

See Part 2. 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. 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) using ASSIST or other electronic submission systems. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply- 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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in How to Apply - 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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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.

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?

Specific to this NOFO: 

• To what extent does the Center address multiple TMDs and comorbidities using a whole-person perspective, with interdisciplinary project(s) requiring a team with complementary expertise to answer research question(s) of broad scope that single R01-like research projects cannot address?
• To what extent will the Center accelerate and advance TMD basic and clinical research, research training, and translation to evidence-based treatments and improved clinical care?
• How well does the applicant provide a sense of the overall impact of the Center to the Collaborative? 

In addition, for applications involving clinical trials

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

Investigator(s)

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

Specific to this NOFO: 

• To what extent does the PD(s)/PI(s) describe expertise in managing large multi-component research programs?
• To what extent have the PD/PI indicated prior collaborative relationships among proposed senior/key personnel and patient/patient advocacy groups at the various sites across the Collaborative?

In addition, for applications involving clinical trials

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

Innovation

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

In addition, for applications involving clinical trials

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

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO:

• To what extent are descriptions of research projects and cores provided? Are the Cores and Research Project(s) cohesive within the Center?  To what extent do the Cores support the Research Project(s)?
• Is the research proposed within the Center translational in nature? If preclinical research only is proposed, is there strong translational potential in the approach?
• To what extent is the organizational structure of the Center appropriate for the scope of the Center?
• To what extent are patient and stakeholder experiences, needs and priorities meaningfully incorporated as partners into decisions?
• To what extent are the plans for the Center to collaborate and otherwise contribute to the Collaborative meaningful?
• To what extent are the plans adequate to ensure and maintain collaborative relationships across multiple research projects and the Collaborative? 

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

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

Specific to this NOFO:

• Do the facilities and scientific and/or clinical environment reflect capabilities for functioning as a major component of a national research Collaborative?
• How well are plans for the Center to collaborate and contribute to the Collaborative such as through Collaborative-wide committees, workshops, meetings, career enhancement, collaborative efforts, or other Collaborative-wide activities and initiatives described?
• To what extent do the letters of support from the lead institution and partnering institutions include a specific commitment to the Collaborative’s goals and define the financial or other resources?  

In addition, for applications involving clinical trials

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

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

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

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

Additional Review Criteria - Overall

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

Study Timeline

Specific to applications involving clinical trials

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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 - Overall

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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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.

Scored Review Criteria - Research Project(s) and Cores  

• Reviewers will provide an assessment of each Core’s strengths and weaknesses and provide a score of acceptable, acceptable with concerns, or unacceptable. The following items should be evaluated while determining scientific and technical merit, and in providing an overall Impact Score for the Core.

Administrative Core 
Review Criteria for the Administrative Core

• To what extent will the Administrative Core promote strategies to ensure robust and impactful scientific outcomes for the Center?
• To what extent do the skills and experience of the Administrative Core PI provide the needed knowledge and experience to facilitate the requirements of the Administrative Core?
• To what extent do the skills and experience of the proposed Administrative Coordinator provide them with the ability to assist the PD(s)/PI(s) and the Administrative Core PI with day-to-day administrative details and program coordination?
• To what extent does the leadership experience and expertise provide the Administrative Core with the management and coordination skills needed for success for a large Center?
• To what extent does the Admin Core strategy section include plans for management of daily activities, establishing policies and procedures, and monitoring progress toward milestones?
• To what extent is a communication and participation plan included for all personnel that details coordination of activities and contribution of collaborating investigators institutions, and patient advocacy groups?
• To what extent are there descriptions of how the various Cores will work collaboratively with the other Cores to coordinate and support efforts across the Center and Collaborative?
• To what extent is there a description of plans for coordination and management of all regulatory and clinical documents in collaboration with the NIH?
   

Bioinformatics and Data Science Core (BDSC)

Review Criteria for the Bioinformatics and Data Science Core

• To what extent are plans included for the BDSC to conduct research in the form of secondary data analyses of existing national population health data and data generated by the Center research projects?
• To what extent are plans included on how BDSC will employ AI/ML/DL approaches to integrate multi-modal data to identify potential therapeutic targets, prognostic models, molecular phenotyping and patient stratification, ontology, CDEs, and other critical applications?

Outreach, Training, and Education Core (OTEC)
Review Criteria for the Outreach, Training, and Education Core

• To what extent does the application include the description of the OTEC Leader’s commitment and track record of training and career development of women, under-represented minorities, and people with disabilities?
• To what extent are the individuals with bioinformatic expertise who will collaborate across the Collaborative identified in the application?
• Within the OTEC, are plans included for the development of curricula and educational resources focused on teaching new knowledge gained that may not have been part of established courses in professional schools? If so, is there a description of how these materials will be directed towards lay persons to clinical specialists?
• To what extent does the OTEC include plans for training of the next generation of interdisciplinary researchers to ensure a pipeline of early career, diverse investigators who will form the future of the community?
• To what extent are there plans to develop mentorship and individual career development plans of early-stage career researchers/trainees under mentors who are part of this Center?
• To what extent are details included of the nature of the ongoing relationships with patient advocacy group(s) and the approach of patient or stakeholder participation across the planned objectives?
• How well does the applicant describe how patient and stakeholder experiences, perspectives, needs, and priorities will be meaningfully incorporated as partners into decisions and activities of the Collaborative?
• How well does the applicant describe the plans for dissemination activities? To what extent will public workshops be used to disemminate information?

Research Project(s)

Review Criteria for the Research Project(s)

• To what extent do each of the included Research Projects have a clear hypothesis to be tested that is relevant to the Collaborative?
• To what extent do each of the included Research Projects describe how the individual research project's goals will address the central objectives of the Collaborative?
• To what extent do the proposed research projects address the gap in TMD research and substantively improve TMD patient care?
• Is a description of how the perspectives of patients and stakeholders included in the work proposed?
• Is the source of CDE used in the study and how it will be coordinated across the Collaborative described?
• For projects conducting research with human participants, is a description included for use of validated and structured questionnaires, for example the questionnaires responsive to the HEAL Common Data Elements for pain measures?

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 policies and practices, 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 NOFO.

Applications will be assigned to NIDCR. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access their 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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 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 recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Defining objectives and approaches to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies.
• Overseeing study conduct, including data collection and analysis, quality control, and resulting publications.
• Cooperating with other PD(s)/PI(s) and the NIH staff members, as appropriate for the goals of the program.
• Adhering to the NIDCR Clinical Terms of Award requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study;
• Serving as Center Director(s) and responsible for the integration and management of activities within the Collaborative including ensuring data sharing and data use agreements are aligned with Collaborative’s requirements.
• Partnering with patient group(s) and ensuring that a representative from the patients represents the Center on the TMD Collaborative’s steering committee.
• Attending and actively participating in Collaborative activities, including meetings of the Steering committee, Collaborative annual face to face meetings, and various relevant working groups.
• Ensuring clinical trials using Collaborative resources receive prior approval from the NIDCR.
• Ensuring results of the research projects are published in a timely manner.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NIH SME will be assigned and will be responsible for:

• Consulting with the PD(s)/PI(s) regarding achieving U54 milestones.
• Serving on the TMD IMPACT Collaborative Steering Committee (SC)
• Advising the recipients on matters related to the technical performance of the projects.
• Monitoring the progress and performance of the awardees.
• Ensuring proper collaboration between the Centers and across the entire Collaborative.
• Informing the NIDCR Program Officer as well as the Collaborative SC of any challenges or delays in project progress.
• Enlisting additional technical experts as necessary from within the NIH, and other government agencies, to review scientific progress and administrative requirements to ensure compliance with NIH policies and procedures.   

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

NIH staff will have joint responsibilities with Centers PIs, Chairs, and patient advocates/groups through the Steering and Executive Committees. The TMD IMPACT Collaborative Steering Committee is composed of NIH PO(s)/Subject Matter Experts (SMEs) from participating ICOs (where appropriate), Centers PI(s) (including research project PIs and Core PIs) Patient and/or Patient Advocate Group, and Working Group Chairs. The SC will identify scientific and policy issues that need to be addressed at the Collaborative level and review and approve all Collaborative-wide policies. It will also ensure dissemination of program data, education and outreach and other materials to the wider scientific community. The SC may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific Collaborative functions as needed.  The TMD IMPACT Collaboratie Executive Committee is composed of NIH PO(s), Center Contact PI(s), SC Chairs, and One Patient Advocate Group Representative, each with voting power to review and approve all Collaborative-wide policies. The NIH POs will participate as a non-voting members. 

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. 

• 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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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: https://www.era.nih.gov/need-help  (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: 301-480-7075

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

Melissa Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-6570
Email:melissa.ghim@nih.gov

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

Aron Marquitz, PhD
NIAMS - NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Phone: (301) 435-1240
E-mail: marquitzar@mail.nih.gov

Alex Tuttle, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-814-6115
Email: alex.tuttle@nih.gov

Guoying Liu
NIBIB - NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
Phone: (301) 594-5220
E-mail: liug@mail.nih.gov

Michael L Oshinsky
NINDS - NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Phone: 301-496-9964
E-mail: michael.oshinsky@nih.gov

Karen Wylie, PhD
Office of Research on Women’s Health (ORWH)
Tel: 301-827-1808
Email: karen.wylie@nih.gov 

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

Gabriel Hidalgo, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4630
Email: gabriel.hidalgo@nih.gov

Erik Edgerton
NIAMS - NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Phone: 301-594-7760
E-mail: erik.edgerton@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.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.