National Institutes of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute on Aging (NIA)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Neurological Disorders and Stroke (NINDS)
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UC2 High Impact Research and Research Infrastructure Cooperative Agreement Programs
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The purpose of this Funding Opportunity Announcement is to solicit cooperative agreement applications from interdisciplinary teams that will cooperatively form the Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN). The goal of RE-JOIN will be to define the innervation of the different articular and peri-articular tissues that collectively form the joint (including bone, cartilage, synovium, joint capsule, ligament, tendon, fascia and muscle), by sensory neurons that mediate the sensation of pain. Knowledge about the types and distribution of neurites in joint tissues will facilitate the identification of key receptors and mediators that induce pain by activating specific sensory neurons. These mediators and their receptors will provide novel targets for reducing pain.
Each Research Team will conduct a research project to map the sensory innervation of the joint tissues in animal models, human tissues, or both. Research Teams projects must focus on at least one of the high priority joint types listed in the FOA and are encouraged to include a description of specific plans to extend the project to other joints and, if the primary focus is animal models, to human tissue. This FOA also provides the opportunity to further adapt or develop technologies that would improve the ability to map neurons in joint tissues.
Data harmonization, integration and visualization will require extensive coordination between teams. The goal will be to integrate data from the different teams to produce models of innervation in different joints.
March 11, 2022
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| April 11, 2022 | Not Applicable | Not Applicable | July 2022 | August 2022 | September 2021 |
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 Funding Opportunity Announcement.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
The purpose of this Funding Opportunity Announcement is to solicit cooperative agreement applications from interdisciplinary teams that will work together to form the Restoring Joint Health and Function to Reduce Pain Consortium (RE-JOIN). The goal of RE-JOIN will be to define the innervation of the different articular and peri-articular tissues, which collectively form the joints, by sensory neurons that mediate the sensation of pain. Knowledge about the types and distribution of neurons in joint tissues will facilitate the identification of key receptors and mediators that induce pain by activating specific sensory neurons. These mediators and/or their receptors may provide novel targets for treating or managing pain.
RE-JOIN seeks an integrated, holistic understanding of the innervation of the joint. On one hand, this includes a more conceptual, global understanding of the types of neurons that are present in the tissues and structures (articular cartilage, synovium, peri-articular tendons, ligaments, joint capsules, fasciae, muscles, and subchondral bone) that collectively form the joint and that contribute to the function and health of the joint as an organ. This also includes establishing whether the innervation changes with age, sex, physical activity, and joint degeneration or arthritis. On the other hand, RE-JOIN also seeks knowledge of the individual types of neurites present in these tissues in order to identify mediators of pain as potential targets for translation into new treatments for joint pain. The combination of the knowledge of the differences in the innervation of the different components of the joint and of the differences between individuals will enable precision medicine approaches to treatment based on types of pain and patient characteristics.
Interdisciplinary, collaborative Research Teams will conduct exploratory and discovery projects and will apply current and emerging tissue technologies that probe the structural, functional, and molecular complexities of the sensory innervation of the joint in animal models, human tissues, or both. Research Teams' projects must focus on at least one of the high priority joint types, knee and/or temporomandibular, and are encouraged to include a description of specific plans to extend the project to other joints, and, if the primary focus is animal models, to human tissue. This FOA also provides the opportunity to further adapt and develop technologies that would improve the ability to map neurons in joint tissues.
Data harmonization will require extensive coordination between teams. Harmonization and prioritization of projects and standardization of data elements, data annotation and protocols will be conducted by RE-JOIN investigators and NIH in a short initial planning period to maximize the potential for synergies. The goal will be to integrate data from the different projects to produce models of innervation in different joints. A Data Coordinating Group (funded separately) will work with the Research Teams to harmonize data management and integrate data from different teams. Research Teams are expected to collaborate and work with the integrated dataset compiled by the Data Coordinating Group to produce maps or visualization of the innervation of the tissue of the joints (funds for collaborative projects will be set aside and such projects will be defined post-award). Data will be shared amongst the Research Teams and, as rapidly as appropriate, with the public, through existing NIH portals (also funded separately).
The RE-JOIN Program will produce:
- Maps with the location of the afferent neurites of dorsal root ganglia (DRG) and trigeminal ganglia (TG) sensory neurons involved in joint pain.
- Phenotype of the neurons that supply the joint tissues and the attribution of those neurites to specific types of neurons in the DRG and TG.
- A description of changes in joint neuron with age and how these changes are influenced by sex, physical activity, etc.
- A description of changes in neurons accompanying degenerative and inflammatory changes in the joint.
- An improved understanding of joint-specific vs. shared patterns of changes in innervation with age or disease in different joint types.
- Validation of animal model maps in human tissue.
- Preliminary evidence for target identification of new treatments for joint pain.
- Large, annotated datasets and metadata to be shared under FAIR and Open Science principles.
Background
Recent advances have highlighted the involvement of different tissues and structures that collectively form a joint, including articular cartilage, synovium, peri-articular tendons, ligaments, joint capsules, fasciae, muscles, subchondral bone and bone marrow in the development of different forms of arthritis. Changes in each of these components may contribute to the sensation of pain, which can take different forms in any given joint over time and in different individuals, through activation of sensory neurons that mediate pain in those tissues. Molecules released because of damage or inflammation in joint tissues can directly activate neurites from nerves in the DRG, which leads to central propagation of the pain sensation. These new findings offer the opportunity for novel approaches to treating pain by understanding how these damage-associated molecules from different joint tissues activate pain neurons, focusing on the tissue components common to joints in general.
Emerging data indicate that sensory and sympathetic nerve fibers and their neurotransmitters affect the development and normal function of cartilage, subchondral bone, and other joint tissues and that the innervation changes under disease conditions. For example, normally there is little innervation of healthy cartilage in the knee but, in osteoarthritis, nerves and blood vessels pass through channels in the subchondral bone and enter the cartilage. Neo-innervation has also been demonstrated in degenerated intervertebral discs in the spine. Thus, innervation in the joint is dynamic, not fixed, and this raises the question of what other factors, such as age, sex and physical activity, as well as degeneration, might alter innervation of the different tissues, and thereby the sensation of joint pain. Because of the significant burden of arthritis involving them, RE-JOIN has prioritized the study of the knee and the temporomandibular joints but inclusion of other joints (e.g., other extremities and spine) may be proposed. A primary goal is to understand the factors that lead to differences in innervation of the tissues of the joint among individuals, such as age, sex, and physical activity. Furthermore, how innervation changes with joint damage is a critical part of this goal. These types of dynamic changes on a global level in the different joint tissues will likely require animal models. Such models also permit linkage of specific neurites in the joint tissues with neurons in the DRG. However, the current limited translatability of animal pain models to humans mandates the direct study of human tissues as well.
RE-JOIN is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.
The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.
Joint pain is cited by most individuals with Opioid Use Disorder as a contributing factor in their use of opioids. Understanding the type and distribution of sensory neurons in the different joint tissues is the first step in identifying interventions to modulate the activation of these neurons in order to reduce joint pain, prevent the progression of joint deterioration, and, ultimately, restore healthy joints. This includes understanding the factors leading to alterations in innervation and the pathways shared across different types of joints.
Structure
To achieve the goal of RE-JOIN, recipients are expected to use team science approaches requiring the interaction of experts from various disciplines. Research Team projects will analyze animal models and/or human tissues to establish the neurobiology of the sensory/joint interface. The focus of the project for each Research Team will be the mapping of sensory neurons in one or more joints, with a primary focus on the knee and/or the temporomandibular joint but the analysis of additional joints may be included. Research Teams may propose, as an optional element, the adaption or development of new technical approaches to mapping nerves in joint tissues. Research Teams are responsible for management and quality control for the data they produce. Research Teams are encouraged to propose methods for visualization of the nerves in the tissues of the joints.
The Research Teams will work together to form the RE-JOIN Consortium. The Research Teams will collaboratively engage in analyses and broad sharing of biological data, methodologies, and disease models prior to publication consistent with the overarching goals of the program. As members of the Consortium, the Research Teams will cooperatively define shared data elements and annotation and develop standardized protocols during the short initial project planning period. Research teams are expected to work collaboratively with the Data Coordinating Group and should identify a team member specifically charged with curation.
A Data Coordinating Group for managing the data across the network will be funded separately. This will include support for the sharing of data, models and analytical tools across Consortium projects. This will include coordinating network-wide definition of common data elements and data annotation working with the Research Teams. A key function of the Data Coordinating Group will be to integrate data produced by the Consortium.
The data generated by the Consortium will be deposited in a data repository, using established NIH resources, for use by network investigators and the public.
The RE-JOIN Consortium will be organized and led by the following:
- RE-JOIN Steering Committee (RE-JOIN SC): Composed by Research Teams' principal investigators and the NIH Project Officers and Coordinators, the RE-JOIN SC will have responsibility for collaboratively formulating research priorities, and for helping to develop, finalize, and implement all collaborative projects.
- RE-JOIN Executive Group (RE-JOIN EG): Composed by representatives from each of the elements of RE-JOIN, animal model, human tissue, technology development, data management and integration, and visualization, as well NIH program staff. The RE-JOIN EG will be responsible for ensuring that the objectives and priorities of the Consortium are achieved.
- RE-JOIN Chair: The Chair will lead the RE-JOIN SC and the RE-JOIN EG. Together with the SC and the EG, the Chair will be responsible for leading the development of the collaborative and harmonization activities of the Consortium. As part of this process, the Chair will engage with other stakeholders, including Institute and HEAL staff. NIH will name the Chair for the initial project period.
Inclusion of early-stage investigators and scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems and is strongly encouraged. There are many benefits that flow from a diverse NIH-supported scientific workforce, including fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for details.
Objectives
The primary objective of the RE-JOIN Consortium is to develop a high dimensional understanding of the distribution of neurons in normal and diseased tissues from animal models and human joints. Additional studies that would also contribute to the overall goals may be proposed, such as studies of mediators that activate the nociceptive neurons, the physiology of the neurons in the joints and the DRG or TG, and the interface between changes in innervation with immune or vascular changes that might contribute to joint pain or health. The work will lead to new insight on the changes in the integration between sensory neurons and joint tissues that are associated with joint pain and how the nervous system contributes to joint homeostasis.
The multidimensional objective includes understanding conceptually, at a global level, the networks of distinct types of neurons in the different tissues and structures of different joints and whether these change with age, sex, physical activity, and joint degeneration or arthritis. This also includes, at a different, perhaps microscopic, level, identification of the types of sensory neurites in the joint tissues and structures, and thus the receptors and mediators that activate them, with the goal of clinical translation into new therapies for joint pain. These two objectives may require different approaches. The global, more conceptual level understanding might profit from reporter constructs expressed in specific types of neurons, or similar tracer technologies, available only in certain animal models. On the other hand, the translational objective might be better served by studying human tissues, or animal models that more closely approximate the anatomy and function of human joints. Either or both approaches are encouraged.
RE-JOIN has prioritized the study of the temporomandibular and knee joints, and one or both of these must be the primary focus because arthritis or degeneration of these joints is a significant cause of chronic pain. However the study of additional joints, such as the spine, may be proposed, in order to understand sensory neuron innervation commonalities and differences in health and disease among the various joint types.
Projects using animal models are expected to assess changes in innervation based on sex, age, and physical activity. Projects using human tissue should identify the types of nerves in the various components of the joint, whether healthy vs diseased tissue samples, and capture basic donor phenotypic information such as age, sex, race, disease severity, etc., as agreed upon by the Consortium post-award.
NIH expects that the objectives of the Consortium will evolve after award to address the global goals, gaps and opportunities that may be generated by the awardees and other scientific groups including those that are part of HEAL.
Specific objectives include:
1. Research Project - Mapping of Neurons in Joint Tissues
The projects must include a plan to map the frequency and distribution of neurites from sensory neurons throughout the tissues and structures that comprise the joint. The plan should also establish the dynamic changes in sensory neuron maps related to age, sex, and physical activity, and identify changes in structure and distribution of sensory neurons and DRG and TG neurons that occur with tissue degeneration and inflammation in arthritic joints using animal models and/or human tissues.
Research must focus on at least one RE-JOIN high priority joint type: the knee or the temporomandibular joint. Additional joints (e.g., other extremities and spine) may also be included. For projects that study only one joint type, applicants must include a plan to expand the proposed approach to a different joint type. All animal model applications must discuss how the findings and approaches can be extrapolated or applied to the study of human tissue and disease. Studies in humans must include capture of the patient phenotype (e.g., age, sex, physical activity level and the degree of joint degeneration, as agreed to by the Consortium).
Awards for Research Teams will include a planning/exploratory period to demonstrate that the site can interrogate existing animal models and/or human tissue samples using current state-of-the-art methods. The planning period will be used to establish project specific and shared protocols for quality control, data annotation and harmonization to ensure future interoperability of datasets. Collaborative Consortium projects will also be identified during the course of the project.
Additional areas of interest include, but are not limited to:
- Determine the function or physiology of the sensory neurons in the tissues and structures of the joint.
- Define the types and mediators of interactions of neurons with other cell types in joint tissues.
- Identify the mechanisms underlying changes in structure, distribution and function of sensory neurites and DRG and TG neurons that occur with tissue degeneration and inflammation.
- Identify the changes in structure, distribution and function of sympathetic system neurons that occur with tissue degeneration and inflammation.
- Identify changes or ingrowth of the vascular system that accompanies changes in nerves in the setting of joint degeneration.
- Determine the molecular pathways involved in the generation of pain associated with structural and functional changes in sensory innervation in joints affected by degenerative and inflammatory changes.
- Elucidate mechanisms of aging-related changes in sensory neurons in joint tissues, and the impact of such changes on pain-related outcomes.
2. Technology Adaptation and Development
Applicants are encouraged, but not required, to advance the science and goals of RE-JOIN through the development or enhancement of innovative technologies and approaches. Technologies applied, adapted or developed with the goal of studying human joints are strongly encouraged. Projects solely focused on developing technologies for the study of animal models must include a discussion of how the technology could be adapted for use on human subjects or human tissue samples. Teams should discuss any dependencies and propose alternative approaches or contingency plans if needed.
Areas of interest include, but are not limited to:
- Technologies that can be extended to probe multiple joint types.
- Technologies that significantly advance the ability to assess sensory neurons in dorsal root ganglia (DRG) and trigeminal ganglia (TG) that extend to joint tissue.
- Technologies that significantly advance the ability to assess sensory neuron density, distribution and plasticity throughout the joint in humans at a larger scale or in vivo.
- Technologies that facilitate the identification of mediators that activate sensory neurons in situ and increase our understanding of how damage-associated molecules from different joint tissues activate pain neurons.
- Use of microphysiological systems, tissue on a chip, and biofabricated systems to model nociception in joint structures.
- Technologies that advance our understanding of the mechanism of induction of joint pain.
3. Collaboration and Sharing
Investigators will work collaboratively within the RE-JOIN Consortium on shared research objectives, data curation and harmonization efforts, and data visualization. This will allow comparisons of shared and unique innervation patterns across the joint types. In addition, the data generated by the different Research Teams will be integrated, to the extent possible, with common annotation and metadata, to produce a dataset for public access to enable the subsequent research and visualizations by the community, a key objective of RE-JOIN.
Research Teams are responsible for the quality control of the data they produce. They must work cooperatively with the Data Coordination Group and must share the data and samples they acquire to support collaborative studies within the Consortium. The Research Teams will work with the Data Coordination Group through the committee structures to develop a policy for public access to the data.
The Data Coordination Group, funded separately, will oversee the coordination between Research Teams with respect to the establishment of common elements based on agreements between Teams. It will oversee quality control metrics for tissue samples, processing, and analytic methods to ensure high-quality standards, and minimize experimental and non-experimental variation. The Data Coordination Group will be responsible for data management. The Data Coordination Group will work with the Research Teams to develop methods to combine data from complementary techniques (e.g., optical images and omics) and manage data integration across the Consortium. Research Teams should identify a staff member charged with curation.
Funds will be set aside for collaborative efforts to be determined post-award. Objectives for the Research Teams include:
- Work collaboratively as a member of the RE-JOIN Consortium to identify important scientific and technology challenges to be addressed collaboratively, including quality standards for shared methodologies and reagents.
- Develop new methods for combining and integrating complementary data and the analysis of the integrated dataset, including quality assurance measures.
- Use the integrated datasets managed by the Data Coordinating Group to create maps or models or other means of visualizing the innervation of the structures and tissues of the joint.
All applications are expected to address Collaboration and Sharing objectives.
Applicant teams are encouraged to consider including Collaborative arrangements with other HEAL projects such as Back Pain Consortium Research Program (BACPAC) (https://heal.nih.gov/research/clinical-research/back-pain), the Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) (https://commonfund.nih.gov/SPARC), the NIH BRAIN initiative (https://braininitiative.nih.gov/), the NIH Blueprint (https://neuroscienceblueprint.nih.gov/), and the Tissue Chip Initiatives & Projects (https://ncats.nih.gov/tissuechip/projects).
Applications that do not have a primary focus on temporomandibular or knee joints; and on the innervation of multiple tissues and structures within those joints, will be considered non-responsive.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NIH intends to fund an estimated 4-6 awards, corresponding to a total of $8,000,000, for fiscal year 2022. Future year amounts will depend on annual appropriations.
Application budgets are limited to $1.6M Direct Cost per year. Budgets should include expenses for costs for two Consortium-wide activities. This must include $100,000 Direct Costs for administration of the Consortium and, in years 4 and 5 only, $250,000 Direct Costs for Consortium-wide collaborative projects.
The UC2 is limited to five years.
Pre-Application Webinar
NIH will hold a pre-application informational webinar for this FOA. Date, time, and other details for the webinar will be posted here.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
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
- 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 Government
- 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 Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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 SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- 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. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
- Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 underrepresented racial and ethnic groups as well as individuals with disabilities 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 SF424 (R&R) Application Guide.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Names of other key personnel
- Participating institution(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
RE-JOIN
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Attachments:
Overall Project Timeline (Required 1 page maximum):
Applications that exceed this limit will be withdrawn. This attachment should be entitled Timeline.pdf . Applicants should include a project timeline in the form of a Gantt chart or similar that includes all major tasks to be performed during the project. The chart should also include estimated start and completion dates for those tasks and should identify the contributions expected from each PD/PI toward accomplishing each task.
Technology Development Plan (Optional - 6 pages maximum):
The overall Technology Development or Enhancement Strategy is limited to 6 pages and should include the Technology Development Plan Milestones and Timelines. This attachment should be entitled "Technology Development Plan.pdf".
Clearly describe the goals of the Technology Development Plan and discuss how the technology will enhance the Center’s research project and advance the understanding of joint pain activation.
Describe the approach and how this Plan will help overcome current hurdles in processing, imaging and advanced analysis of tissue innervation.
Provide any data supporting the development or enhancement of the technology proposed, its applicability and translatability, e.g., to humans and or to other joint types.
Provide a statement of the advantages of the proposed technology compared to existing technologies.
Provide a lay description of the value of the project, including key technology objectives.
Technology Development Plan Milestones and Timeline.
Provide a clear description of all interim objectives (research and/or developmental milestones) to be achieved during the course of the project.
Identify any impediments or dependencies that could require a revision in the work plan or milestones with a discussion of alternative approaches.
Discuss criteria by which each milestone achievement will be assessed.
Provide a timeline for the anticipated attainment of each milestone and the overall goal(s).
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
To be successful, projects of this level of complexity are expected to require significant effort from all PDs/PIs involved. The contact PD/PI is required to devote at least 10% of their time available for research to this award, while other PDs/PIs are required at least to devote sufficient effort/time to accomplish the goals of the proposed research. Staff charged with curation will need to devote at least 30% effort. The total research effort should include their combined research effort at all institutions where the PD/PI holds an appointment, should be expressed in person-months, and should not include time expended toward teaching, administration not directly related to the PD's/PI's research, and/or clinical duties.
Certain supporting functions such as equipment, animal research costs, and clinical research costs may be requested if well justified and unique to the institution(s) involved. Within the research budget, equipment, including equipment for data sharing and management, can be included if well justified. Equipment that duplicates existing institutional or regional shared facilities that are available to investigators must be identified and the proposed duplication should be well justified.
Include support for the activities as member(s) of the RE-JOIN SC, including in-person travel to Bethesda MD/Washington DC area at least two times per year throughout the project period, including the launch meeting anticipated in November or December of 2022. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.The budget should include a line item for Consortium-wide administrative costs of $100,000 This line item would cover costs (including dedicated personnel) associated with providing operational management, and coordination of consortium-wide activities including but not limited to:
- Providing support to the chairs of the Steering and Executive Committees, and future working groups including planning and arranging meetings.
- Establishing and maintaining effective communications across the consortium to ensure the members understand their roles and responsibilities and are kept abreast of the scientific and procedural development in the program.
- Coordinate development of and adherence to network-wide policies and procedures.
- Track data and adherence to timelines.
- Assist with the planning and submission of manuscripts for publication.
The budget should also include a line cost item not to exceed $250,000 Direct Cost/year for the last two years of the project for Consortium-wide collaborative projects. These costs will be counted as part of the $1.6 Million Direct Cost cap.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Provide the overall goals for the entire project.
Research Strategy: Organize the Research Strategy in the subsections identified below.
1. Background and Significance
- Discuss the potential of the mapping approach and the technology or analytic tools proposed for the discovery of innervation of the joint.
- Address how the proposed mapping approach and the technology/analytics proposed may help resolve how neurons relate to the tissues and components of the joints (e.g., articular cartilage, synovium, peri-articular tendons, ligaments, joint capsules, fasciae, muscles, subchondral bone and bone marrow).
- Discuss how the findings could be extended to the study of joints that are not the primary focus of the application (e.g., if the knee is the primary focus, how could the approach be extended to the TMJ or other joints?).
- If the primary focus of the application is on animal model(s), discuss the potential to apply the proposed approach/technology to normal and diseased human joints.
- Discuss how the results could lead to the identification of targets for pain intervention.
- Discuss the limitations of the proposed strategy.
2. Activities and Management of the Research Team
- Clearly describe the formal organizational structure of the multidisciplinary team, including lines of authority and responsibility, with attention to the relationship of the organizational structure to the major objectives of RE-JOIN.
- Document the collaborative research experience of the team, and the consideration and incorporation of varying perspectives in decision making..
- Document willingness to accept the overall governance, common protocols, publication policies, collaborative procedures, confidentiality and data sharing plans to be developed by the RE-JOIN Consortium.
Confirm willingness to attend RE-JOIN Consortium meetings virtually and in the Bethesda MD/Washington DC area twice yearly. Applicants should also state their willingness to work collaboratively with the other RE-JOIN investigators on conference calls, working groups, IC meetings, and in the dissemination of research findings through publication or presentation and their willingness to cooperate and coordinate their activities after awards are made by participating in an annual HEAL Investigators Meeting, as well as other activities.
3. Preliminary Data
- Summarize preliminary data documenting the performance metrics and robustness of the proposed method(s) and next generation assays, including sensitivity, specificity, level of detection, accuracy, variability, depth/completeness and validation metrics.
- Demonstrate how proposed technologies can support the RE-JOIN objectives, which might include identification of cell types, different cell states, identify cell and tissue region heterogeneity, neuropeptides, neurotransmitters and/or other mediators involved in pain sensation in normal and diseased joints.
- Indicate how the data can be mapped back to tissue for spatial location and can be correlated with disease or, for human studies, with clinical phenotype.
- Discuss other sources of existing healthy or diseased samples (including archived tissue) to be used for optimization, discovery, and validation efforts. (Note: any existing data or samples discussed in the application must be made available to the RE-JOIN Consortium upon award.)
- Document willingness to share all data and samples, as appropriate, and discuss how they will be harmonized.
- Indicate how the proposed methods and technologies complement each other, if applicable.
4. Approach
- Applicants should propose an approach to mapping the innervation by sensory nerves of the tissues and structures that collectively form the joint.
- Applicants should propose mapping of the knee and/or the temporomandibular joint but may propose mapping of other joints (e.g., other extremities, the spine). The joint(s) to be studied must be conducted in animal models and/or human tissues.
- Applicants who propose studies of animal models should include approaches for analysis of changes in sensory innervation with age, sex, and physical activity and should include studies of changes in innervation in animal models of joint disease. Applicants who propose studies of human tissues should include, if possible, approaches for collection of data on the phenotype of the individual (e.g., age, sex, physical activity: final set to be determined by the Consortium post-award) and the extent of joint degeneration.
- Applicants should justify the approach(es) to interrogate animal and/or human joints tissue/specimens. Applicants should propose specific milestones for each approach.
- If applicants propose to study animal models, then applicants should provide evidence of the relevance of the animal model to human joints and should provide a description of how the results in animal models can be validated in human tissues.
- Propose methods to overcome current hurdles in processing, imaging and advanced analysis of tissue innervation.
- Discuss the data to be generated (type, file size, and estimated bytes), plans for optimization, validation, and quality control for the proposed approach and data generated by the Research Team.
- Discuss any bioinformatics, statistical analysis and computational modeling required for primary analyses.
- Discuss plans to contribute to data harmonization, alignment of protocols and data sharing with other members of the Consortium.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data),all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that data generated by HEAL Initiative-funded projects will be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem.
To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:
- Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
- Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.
- All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL Clinical Data Elements (CDE) Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C 794 (d)), which require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities. HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.
As part of the response to the public health emergency of opioid use disorder and deaths, a key objective of RE-JOIN is to make the data produced by the Consortium available to investigators outside of the Consortium as rapidly as possible. The RE-JOIN initiative will require extensive data sharing via infrastructure identified by the NIH. Data objects (raw data, processed data, analysis routines, etc.) will be shared through a platform, curated by a Data Coordinating Group (funded separately) and made available to the public via a supported portal. RE-JOIN awardees will be expected to share data in a timely fashion (potentially pre-publication) and conform to existing data standards and sharing practices (for example, see here). Data sharing and curation are expected to be significant amounts of work, and applicants should budget accordingly for these tasks. To this end, the RE-JOIN Steering Committee, which includes RE-JOIN investigators and NIH staff, coordinated by the Data Generation Center, will generate a plan for doing so. The plan will then be reviewed and approved by the RE-JOIN Executive Committee and the NIH Institutes and Centers. Agreement and compliance with the plan will be a condition for release of restricted funds to awardees.
The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.
- Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
- NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
- NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009)
- NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
- NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.
Recipientsconducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Institutions
Not Applicable
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof 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. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
For this FOA:
Does the project, if accomplished, advance the stated goals of the RE-JOIN program?
Are the proposed animal models, human work, and technical innovations likely to contribute meaningful new information and approaches to the understanding of joint innervation and pain?
For applications proposing animal models, is a meaningful path proposed to understand the relevance of the findings to human joint innervation in health and disease?
For studies on human tissues, are the donor populations sufficiently phenotyped and relevant to understand innervation in normal and pathologic conditions?
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?
For this FOA:
Does the team bring a diversity of expertise to achieve the goals of the individual Center and the collaborative, overarching goals of RE-JOIN? Is it clear that each investigator is necessary and will contribute to achieving the goals of the program? Does the investigator team have enough expertise with the models to be studied? Is there evidence for synergistic interactions among PDs/PIs? Are staff identified who will be able to manage, curate and perform quality control on the data produced by the Team and harmonize and share that data with the Consortium? If the application includes collaborating investigators who will not receive direct support, is it clear how these investigators will participate in the program?
Does the description of the organizational structure give one confidence that fair and adequate governance processes will be used for decision making; and that all/multiple perspectives will be considered in doing so? Does the plan allow for flexibility in pursuing the aims and allocation of resources? Does it provide for effective team leadership and management with distributed responsibility and decision-making processes?
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?
For this FOA:
Does the project include innovative ideas or approaches to analyze joint structures and tissues? Does the application propose emerging and novel technologies to conduct anatomical and functional maps of sensory innervation of the joint? Does the strategy reflect consideration of the joint as an organ, that includes several structures and tissues? Does the research proposed involve innovative combinations of approaches from different disciplines to address its goals?
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?
For this FOA:
Will the approach lead to a holistic understanding at a global level of the sensory innervation of the different tissues and structures that collectively form a joint, and whether these change with age, sex, physical activity or joint degeneration; and/or provide knowledge about the specific types and distribution of neurites in different human joint tissues and structures that will enable the identification of key receptors and mediators that induce pain and thereby facilitate the development of new approaches to treating pain?
Is the proposed use of animal models, human tissue or both adequately justified and timely?Is there evidence that the investigator team has access to a sufficient number of high-quality specimens to conduct studies of innervation of the joint?
If the application proposes to focus only one joint or only on animal models, is the path to extend the observations to other joints and/or human tissue discussed and scientifically sound and feasible? Does the approach include consideration of sex and age as biological variables? If appropriate, will plans for technology development enhance the goals of the proposed projects or the broader overarching goal of RE-JOIN?
Are the timeline and milestones proposed to evaluate progress appropriate for accomplishing the specific aims?
Is the plan for dissemination of the results to the broader biomedical research communities sufficient?
Is the Data Management and Sharing Plan appropriate?
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?
Additional Review Criteria
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Not Applicable.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Sharing Model Organisms; and (2) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAMS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
As part of the scientific peer review, all applications:
- May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Arthritis, Musculoskeletal and Skin Diseases Advisory Council. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, 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.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 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.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 754, 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 recipientsis anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipientsfor the project as a whole, although specific tasks and activities may be shared among the recipientsand the NIH as defined below.
By accepting an award, the PI and Institution agree to become part of RE-JOIN. The work to be carried out under the award will be conducted collaboratively with other members of RE-JOIN and the NIH and will be subject to review and approval by the RE-JOIN SC prior to full implementation as specified in this RFA. NIH expects that the work of the Consortium will evolve after award to address the global goals, gaps and opportunities that may be identified by the awardees and other scientific groups.
ROLES AND RESPONSIBILITIES
The PD(s)/PI(s) will have the primary responsibility for:
- Advancing and coordinating the activities at their Research Teams, scientifically and administratively.
- Serving as a voting member of the RE-JOIN SC.
- Participating actively in the formulation and implementation of RE-JOIN.
- Actively participating RE-JOIN activities and groups.
- Implementing common data elements, protocols, standards, and policies defined by the curation and harmonization component of RE-JOIN in collaboration with investigators or as required by NIH/NIAMS or HEAL.
- Providing data as directed by NIH using procedures and standards recommended by the curation and harmonization protocols.
- Sharing data publicly through dbGaP or other public portals designated by NIH, as appropriate and consistent with achieving RE-JOIN goals.
- Establishing procedures within the center and affiliated sites to ensure that all members of that center are aware of, and conform to, the data sharing and other resource-sharing plans.
- Establishing procedures within the center to ensure that all members of that center conform to the data sharing and other resource-sharing plans.
The NIH Project Scientist(s) will have substantial involvement that is above and beyond the normal stewardship role in awards, as described below:
- Cooperation and coordination with recipients in performance of project activities.
- Facilitate collaborations with and access to other NIH-supported research resources including those supported by HEAL projects.
- Share information regarding promising new agents, strategies, and developments when appropriate.
- Identify scientific gaps and organize meetings to facilitate exchange of scientific and regulatory information.
- Serve as liaison/facilitator among recipientsand with the data portals such dbGaP.
- Participate on the Investigator Committee as voting members and help coordinate RE-JOIN SC activities and implementation of its recommendations, decisions, and policies.
The NIH Program Official will be named in the Notice of Award and will be responsible for the normal scientific and programmatic stewardship of the award, as described below:
- The Program Official will interact with the PI(s) on a regular basis to monitor progress. Monitoring may include regular communication with the PI and their staff, periodic site visits for discussion with the recipient Research Team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship matters.
- Work with the PIs to develop performance milestones for the individual awards.
- Aid the RE-JOIN SC in the development of procedures for evaluating the performance of research studies.
- The Program Official may also identify other extramural staff who have appropriate experience and expertise to assist with the management and proper stewardship of the award.
An NIH Grants Management Specialist will be named in the award notice. A Grants Management Official will attend the SC meetings as a non-voting observer.
Areas of Joint Responsibility include:
Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage, assess, and disseminate the RE-JOIN consortium.
All participants in the RE-JOIN consortium agree to work collaboratively to:
- Provide for secure, accurate and timely data submission.
- Participate in presenting and publishing new processes and substantive findings.
- Assess and disseminate RE-JOIN data and resources.
- Participate in the governance of the RE-JOIN consortium as a member of the RE-JOIN Steering Committee.
- Interact with other relevant NIH activities, as needed, to promote synergy and consistency among similar projects.
Steering Committee
RE-JOIN Steering Committee members will include PD(s)/PI(s) from each award, other staff as needed, and NIH Program Staff. The voting members of the Steering Committee include a single PD/PI from each award and NIH Project Scientists or Coordinators. Note that although awardees may choose to utilize the multi-PI mechanism, each will have only one vote in all SC. NIH representatives will be voting members, but will not serve as the Chair of the Steering Committee, or in aggregate represent no more than 1/3 of the total voting membership of the SC. All major scientific decisions will be determined by majority vote of the SC. All participants in the RE-JOIN Consortium are bound by the policies and procedures developed by the Steering Committee.
The RE-JOIN Steering Committee will serve as the main scientific body of the program. The RE-JOIN Steering Committee (SC) is expected to meet regularly and will be responsible for coordinating the activities being conducted by the program, and is the committee through which consortium-wide decisions are made. The RE-JOIN SC will collaboratively formulate research priorities, and help to develop, finalize, and implement all collaborative projects. The RE-JOIN SC may establish subcommittees as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The RE-JOIN SC will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.
Executive Group
The RE-JOIN Executive Group will include a representative from each of the elements of RE-JOIN, animal model, human tissue, technology development, data management and integration, and visualization, as well as NIH program staff. The RE-JOIN Executive Group (EG) will meet on a regular basis and is responsible for ensuring that the objectives and priorities of the Consortium are achieved.
Dispute Resolution
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
3. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs 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 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
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Email: [email protected] (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: [email protected]
Leslie K. Derr, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-8174
Email: [email protected]
Michael L. Oshinsky, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]
Julia L. Bachman, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-7383
Email: [email protected]
Devon Oskvig, PhD
National Institute on Aging (NIA)
Phone: (301) 496-9350
E-mail: [email protected]
Melissa M Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: (301) 529-6570
E-mail: [email protected]
Guoying Liu
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Phone: (301) 594-5220
E-mail: [email protected]
Erin Burke Quinlan, PhD
National Center for Complementary and Integrative Health (NCCIH)
Phone: (301) 451-0636
Email: [email protected]
Kathy Salaita, Sc.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: [email protected]
Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-7760
Email: [email protected]
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Jeni Smits
National Institute on Aging (NIA)
Phone: (301) 827-4020
E-mail: [email protected]
Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: [email protected]
Florence Turska
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Phone: 301-496-9314
E-mail: [email protected]
Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]
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 45 CFR Part 75.
and Human Services (HHS)
