NIH's new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

It is critical that applicants follow the instructions in the Multi-Project Instructions for the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The ultimate goal of this FOA is to address existing and future clinical research needs at the institutional, local, and national level for musculoskeletal, rheumatologic, and skin diseases by fostering the development, implementation, and inclusion of novel data, analytical methods, metrics, and outcome measures into clinical research at the institutional, local, and national levels. Incorporation of metrics and methodologies that result from this FOA into new clinical research, trials, and ultimately patient care will be an important measure of short-and long-term success of a funded Core Center for Clinical Research (CCCR).

This FOA is the result of ongoing efforts by the NIAMS to continually evaluate and improve upon existing programs. Based on internal review, along with the advice of an externally convened Centers Evaluation Working Group (CEWG) and a Request for Information (RFI) that followed, the NIAMS decided that the traditional Multidisciplinary Clinical Research Centers (MCRC) (i.e., P60), originally established in 2001 to promote clinical, epidemiological, and health-services research, needed to be updated. This FOA represents such changes and offers a unique opportunity to advance the methodological sciences that support clinical research within and across the NIAMS' portfolio of diseases.

The NIH definition of clinical research is research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator or colleagues directly interact with human subjects, including epidemiological or behavioral studies and outcomes research and health services research. The focus of this FOA is on clinical research that ultimately, directly or indirectly, impacts upon patient care to make a difference. Ideally, applications submitted in response to this FOA should build on emerging thinking and innovative ideas, such as the surge in 'omics' data, enabling these new approaches to ultimately, meaningfully improve health-related outcomes for patients with skin, musculoskeletal, or rheumatic diseases or conditions.

By design, the NIAMS CCCR are to consist of a strong methodologic core and a more modest administrative research core focused on the support of clinical research. The inclusion of optional additional Resource Core(s), focused on the mission of the CCCR, is encouraged. CCCR PD/PIs have the flexibility to organize the center activities around a central scientific theme or to organize the center activities with more traditional approaches. These CCCRs are envisioned to be flexible, innovative and adaptable, allowing for dynamics in the design, structure, and conduct of the individual components. They are intended to be able to accommodate and address the most pressing needs of the NIAMS clinical research community while keeping in mind existing and/or projected gaps in knowledge, breadth of concepts, and issues of feasibility and adoptability. This FOA will not support core centers (or activities within centers) focused on the generation of biological or genetic data or the development of novel technologies for such generation.

Applicants for CCCRs are encouraged to develop cross-disciplinary resources and are encouraged to leverage available existing resources (e.g., CTSAs) in order to harmonize institutional support for this clinical science, and to advance the goals and objectives of the proposed center. Translating discovery into improved health will require use of optimized, state-of-the-art methodologies (e.g., propensity score matching) and analytics in order to usher in ground-breaking, paradigm-shifting research. For example, by addressing common themes these research cores could contribute toward converting big data into personalized data and thereby inform as well as transform future clinical care. The proposed CCCRs should in some way include efforts addressing the preferences and needs of patients and to include these at all levels of clinical research from conceptualization to implementation. Success will be based on addressing substantial common unmet clinical needs from the perspective of all stakeholders (patients, providers or researcher) and answering important clinical and methodological questions in the NIAMS' portfolio of diseases.

In contrast to prior NIAMS-funded MCRC (P60) FOAs, this FOA will not allow submission of research projects; only cores (P30). Applicants may propose the inclusion of an optional program for Pilot and Feasibility (P&F) studies that would support the goals of this FOA by presenting an initial proof-of-concept and/or contributing to the robust premise for clinical research.

Required elements of a CCCR include:

• A CCCR program for diseases and disorders within the NIAMS mission that would be supported by either 1) a meritorious clinical research base that encompasses specific diseases or conditions (traditional disease focused) or 2) professional and patient-derived resources for developing future clinical projects and improving patient care (theme focused).
• An overall CCCR Director and Associate Director with outstanding credentials for promoting clinical research, clinical trials and/or patient care implementing innovative methodologies.
• An Administrative Core that will 1) play a key role in providing support for innovative and multidisciplinary approaches for clinical projects within the NIAMS mission; 2) contribute to the clinical training environment of the CCCR and 3) attract new investigators into clinical research within the NIAMS mission. The Administrative Core will engage members for an External Advisory Committee to the CCCR, and organize and convene meetings of this body to obtain administrative and scientific input.
• A Methodologic Core that would facilitate the development and implementation of clinical research by providing expertise and support to new and ongoing local projects and other emerging research opportunities elsewhere that are relevant to the NIAMS mission. The Methodologic Core may support outcomes research, epidemiology, clinical trials and /or health services research. While this core is not required to be innovative, it should be "state-of-the-arts" and drive innovation within the clinical research community. Methodologic Cores may play broader roles in more traditional-focused relative to theme-focused centers. However, the incorporation of novel methodologies such as molecular phenotyping of patients for clinical trials or novel uses of biomarkers for patient selection, could be considered with either approach.

Optional elements of a CCCR include:

• A plan for up to two Pilot and Feasibility projects supported by the CCCR, if proposed, should be included in the Administrative Core with a yearly budget of at least $20,000 and up to $50,000 in direct cost per year and lasting no more than three years.
• Additional Resource Core(s) focused on clinical research areas that significantly contribute to the focus of the CCCR and provide innovative support and methodologies to the research community.

The Administrative Core is expected to provide management and leadership for all CCCR activities. The Director of the CCCR, aided by an associate Director, an External Advisory Committee, and the investigators in the Methodologic Core and, if proposed, Resource Cores, provides leadership to assure a rigorous research approach and to focus all clinical projects on critical issues relevant to disease prevention or to assessment and/or to improve patient outcomes. The proposed Director should have leadership skills related to the ability to network with all stakeholders from clinical and other areas of biomedical research. The Administrative core should enhance the environment at the CCCR for clinical research. This may include but is not limited to:

• Provision of leadership at an institutional or broader level for research on the topic of focus by the CCCR;
• Expansion of the research community by attracting new investigators, and established investigators from other fields;
• Enhancement of the clinical research environment and promotion of synergistic clinical collaborations and/or interdisciplinary clinical research.

The Administrative Core will be expected to facilitate interaction between the proposed Methodologic and Resource Cores with those from all NIAMS-funded CCCRs. Efforts should be made for similar cores to cooperate with each other to define and refine how shared knowledge and advances can substantially impact the wider NIAMS' clinical research community through the formation of integrated and possibly synergistic groups. This could be, for example, by frequent communications including webinars, training videos, and regularly scheduled in-person meetings. These interactions should seek to drive synergy, creativity, innovation, and technical advancement toward improving health in all NIAMS mission areas. Fostering training of future clinical researchers will be an important key to guide such educational opportunities.

The Methodologic Core is expected to provide expertise and support to ongoing projects within the research base of the CCCR and to other emerging research opportunities funded elsewhere that are relevant to the NIAMS mission. These efforts should include but are not limited to methodologic and biostatistics design of clinical projects including bioinformatics and maintenance of data integrity, all issues involving patient safety and inclusion, and interfaces with Electronic Medical Records. The Methodologic Core may also provide optimal strategies, including FDA input, for optimization and validation of biomarkers in individual diseases or mechanistically-related diseases that could enhance clinical research or trials and ultimately meaningfully impact patient care. Methodologic Cores may also assist users in the evaluation of the research premises that are at the stage to support submission of clinical trial applications for NIH funding.

Methodologic Cores are encouraged to leverage existing resources, such as existing patient registries, existing clinical cohorts, and existing datasets, and to coordinate with other CCCRs and non-CCCR Core Centers. Whenever possible, generic services, whether existing or proposed, should be customized to meet the needs of the research community. All Cores are strongly encouraged to enhance the value of the resources they offer through education on methodologies and other resources offered by the Core, as well as consultation on study design and data analysis and interpretation. Applicants from institutions that have a Clinical Translational Science Award (CTSA) funded by the NIH may wish to identify the CTSA as a resource for conducting the proposed research and should describe how the proposed Cores leverage these resources.

A single CCCR may propose one or more Resource Cores offering different types of technologies, services, and/or critical resources for clinical research. Although the Cores themselves are not required to be innovative, they should be "state-of-the-art" and drive innovation within the research community. Resource Core support may include personnel, equipment, supplies, services, and facilities. It is expected that the Resource Cores will receive some reimbursement for the cost of providing services or other resources through user fees. This FOA will not support core centers (or activities within centers) focused on the generation of biological or genetic data, or the development of novel technologies for such generation.

Resource Cores are encouraged to leverage existing resources, such as existing patient registries, existing clinical cohorts, and existing datasets. Cores are strongly encouraged to enhance the value of the resources they offer through education on methodologies and other resources offered, as well as consultation on specific application to clinical research. Applicants from institutions that have a CTSA funded by the NIH may wish to identify the CTSA as a resource for conducting the proposed research and should describe how the proposed Cores leverage these resources.

Below are examples, not intended to be exclusive, required, or limiting, of what potential Resource Cores might facilitate:

• Providing strategies for optimization, validation and qualification of biomarkers in individual diseases or mechanistically-related diseases that could enhance clinical research or trials and ultimately meaningfully impact patient care.
• Assistance with selection of optimal premises for supporting clinical trials at different research stages on topics within the NIAMS mission.
• Identification of clinically-relevant inflammatory or musculoskeletal outcome measures and biomarkers for diseases such as spondyloarthropathies, psoriatic arthritis, ankylosing spondylitis, muscular dystrophies, osteoarthritis, and osteoporosis.
• Use and development of innovative strategies to maximize meaningful clinical use of biomarkers (objective) and patient-generated (subjective) outcomes in clinical research and patient care.
• Implementation of innovative statistical strategies such as propensity scoring matching for the development of tailor-made medicine using existing therapeutics for patients within the NIAMS mission.
• Integration and implementation of big data from OMICs analysis at the level of the patient.
• Leveraging mHeath to improve NIAMS-focused clinical research.
• Molecular phenotyping of patients for clinical trials.
• Development of mechanistically, disease-agnostic approaches to improve clinical research and patient care.
• Advancement and improvement of clinical care in regard to health disparities.

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

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

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH's ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the Multi-Project Instructions for the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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:

Justine Buschman, M.S.
Telephone: 301-496-4811
Fax: 301-480-1284
Email: buschmanj@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	12
Methodologic Core (use for Methodologic Core)	12
Resource Core (use for Resource Core)	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of 1
• Methodologic Core: required; maximum of 1
• Resource Core: optional

When preparing your application in ASSIST, use Component Type 'Overall'.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

Facilities and Other Resources: For each institution that is hosting a Core, briefly describe the features of the institutional environment that are relevant to the effective implementation of the proposed CCCR. List institutional resources available to the CCCR and elaborate on how these resources will contribute to the success of the CCCR. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated units, patient populations, geographic distribution of space and personnel, and consultative resources. Include a list of who occupies specific space, the square feet and equipment in that space, and a designation of the CCCR functions associated with the spaces. Applicants may include Campus maps and floor plans to illustrate the physical space available for the proposed Resource Cores and Administrative Core. Describe institutional commitments for space or other resources for the proposed CCCR.

Other Attachments: The following supportive data tables should be included with the Overall Component in order to aid in the review of applications. The filename provided for each attachment will be the name used for the bookmark in the application image.

Table of "Grants Supporting the Research Community":

Without duplicating information provided in biographical sketches, a table listing the grants held by investigators in the research community, their duration, the current year direct cost, and their principal investigators must be included. This table is particularly important for CCCRs that propose Resource Cores. Avoid an exhaustive list of grants with indistinct relationship to the CCCR. It is helpful to group the grants into aggregates of projects with similar overall goals and objectives.

Biographical Sketches of Research Community Investigators:

Title this single attachment: "Research Community Biographical Sketches." Provide biographical sketches for all investigators of the research community, as defined within the application, and organize them alphabetically by the last name of the research community investigator. Do not include duplicate biosketches for Senior/Key personnel. The Personal Statement in the Biographical Sketches may be used to provide details on the research programs of the research community investigators as they relate to the research focus of the CCCR, and to describe how CCCR resources would specifically and directly impact these research programs.

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

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

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

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

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

Introduction to Application: For Resubmission applications (only allowed for the FY2019 due date), an Introduction to Application is required in the Overall component.

Specific Aims: Describe the broad, long-term objectives and goals of the proposed CCCR. Include the objectives for the Administrative Core, the Methodologic core and all other proposed Resource Cores.

Research Strategy: The Research Strategy section of the Overall Component serves to introduce the proposed CCCR, to state the CCCR objectives, and to identify the focus or theme of research addressed in the proposed CCCR. This section also provides reviewers with a sense of the overall significance of the CCCR, i.e., how the CCCR and any unique resources it provides will impact the research community and the field(s) of research covered by the CCCR. For the purposes of this FOA, the research community can be defined as those investigators (with or without funded projects) who will use CCCR resources for research within the focus of the CCCR. Members of a research community may work in the same field or related fields and interact through common meetings, collaborations and shared activities and resources. This section should describe the research community, the significance of the CCCR with respect to the research community and field(s), the proposed interactions among the CCCR Investigators and the Cores, the innovation of the CCCR, the approach for providing core services and resources, and any preliminary data regarding the possible impact of the CCCR on the clinical research community. Preliminary data may include past progress of a previously funded NIAMS Multidisciplinary Clinical Research Center (MCRC) (P60); however, a progress report is not allowed.

The Research Strategy section of the Overall Component should be organized in the following manner:

Orientation to the Overall CCCR

Describe the goals of the CCCR. Describe the scientific, organizational and management structure of the CCCR. Include the leadership structure of the CCCR and the individual Resource Cores. Include the theme or focus of the CCCR, the research field(s) of the CCCR and the research community, any needs assessments that were conducted that led to the selection of resources being shared through the CCCR, and unique aspects of the resources and services being offered by the Cores.

Research Community

Present an overview of the research community and describe how the proposed CCCR will contribute to ongoing activities related to the NIAMS mission. A strong research community is a fundamental requirement for establishing a CCCR. The research community may be defined at the local, regional, or national level (and may include foreign collaborators) as long as it is practical for the members of the research community to utilize the resources offered by the CCCR. The research community for either a traditional disease or a theme-focused CCCR may be defined as: 1) funded investigators with well-defined connections to the disease or theme focus or 2) professional and patient-derived resources for developing future clinical projects and improving patient care for diseases and disorders within the NIAMS mission. This narrative presentation should be organized to address the focus and interrelationships of research conducted by the CCCR investigators (including the research community investigators using the Cores and researchers leading and staffing the Cores) and how the research interests of the investigators in the research community are related to the disease or theme focus of the CCCR. Criteria for designating an investigator as a CCCR investigator should be defined.

The investigators of the research community of the proposed CCCR may be documented in greater detail in the Biographical Sketches (see Other Attachments) and Letters of Support. If the Letters of Support and/or Biographical Sketches are used in this way, they should be explicitly referenced within this section. It may also be useful to highlight ongoing and past successful collaborations between investigators in the research community and the CCCR personnel and to document the outcomes (e.g., publications, grants, major scientific advances, etc.) of these collaborations.

Significance

This section should expand on the goals of the CCCR and should describe the expected effect of the CCCR on clinical research and patient care especially in the field(s) of research chosen as the focus of the CCCR. Include the importance of the resources being shared and the expected effect of providing access to those resources. Explain the degree to which the CCCR is expected to accelerate progress on the aims of the research community grants and projects, improve efficiency and enhance productivity of the research community investigators. Describe how the CCCR will help to expand and enhance the capabilities of the pool of investigators engaged in research related to the research topic(s) of the CCCR. For a CCCR that provides access to a unique highly specialized resource, provide examples of research projects that would be enabled and/or significantly enhanced by access to that resource.

Innovation

Address how the CCCR will not only evolve with the clinical research conducted by the CCCR Investigators but also challenge and seek to advance or change current research or clinical practice paradigms by using novel theoretical concepts, approaches or methodologies, or interventions. Explain how the synergy of the CCCR with the research community will lead to novel approaches to clinical research and development of unique resources in the Cores. For Methodologic or Resource Cores that by nature are not innovative, describe how these may be essential to sustain and advance the field.

Approach

Summarize the services and resources provided by the CCCR, and how they are managed and coordinated. Describe how the CCCR will address the clinical research needs of the research community. Indicate if any of the proposed Cores (Methodologic or Resource) will utilize or expand cores already existing at the participating institutions. Describe how the proposed CCCR will make existing and developed resources broadly available to the research community, leverage existing resources, and fill gaps in the services available for clinical research. Also describe how the CCCR will use activities to expand the research community and promote innovative clinical research on the topic of focus of the CCCR.

Leveraging of existing resources is encouraged, particularly when this provides additional breadth of services or access to resources that would not otherwise be readily available. Furthermore, applicants should demonstrate that support for the existing resource through the CCCR would provide added value to the resource beyond that which would be available by paying for use of the resource through a fee for service or access. Applicants from institutions that have a Clinical Translational Science Award (CTSA) funded by the NIH may wish to identify the CTSA as a resource for conducting the proposed research, if appropriate. Provide details of any interactions between CCCR staff and CTSA staff and/or research personnel describing collaborative linkages being developed.

Letters of Support: Include any letters of support for the proposed CCCR by appropriate institutional officials of each performance site. These letters should include commitments of space and other resources required by the CCCR. A letter of agreement from existing resources (such as the CTSA PD(s)/PI(s)) should be included here if collaborative linkages are being developed between the CCCR and existing resources. Letters from the investigators of the research community or those providing needed resources may be provided to document their research interests, current or planned interactions with other CCCR investigators, the need for and impact of shared resources proposed to be used as part of the CCCR.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study
All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type 'Admin Core.'

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Director' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Personnel of the Administrative Core should include the CCCR Director, who is responsible for the organization and operation of the CCCR, and an Associate Director, who will be involved in the administrative and scientific aspects of the CCCR, and will serve as Acting CCCR Director in the absence of the Director. The Director of the Administrative Core should be the Resource-based CCCR Director. Describe in detail the expertise and qualifications of the Director and Associate Director in the corresponding Biographical Sketches.
• List administrators and staff for the Administrative Core (not individual Resource Cores). If Resource Core Directors also help administer the overall CCCR, list them as well.

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

The CCCR Director is expected to make a commitment of at least 1.8 calendar months (CM) to the overall administration of the CCCR and increased to a total of 2.4 CM for research if the CCCR Director is also the lead of a Core (Methodologic or Resource). Required effort for Methodologic and any optional Resource Core Directors and Associate Directors should equal 1.8 calendar months. The CCCR Associate Director is expected to commit at least 1.2 CM to administration. Administrative support personnel may be requested at no more than one full time equivalent (FTE) which may be divided among one or more positions. This position must be fully justified.

Applications may include up to $2,500 yearly travel expenses in the Administrative Core to pay for two individuals to attend one 2-day meeting related to the CCCR focus.

The budget of the Administrative Core may include appropriate salary for the Director, Associate Director and support personnel, expenses related to the External Advisory Committee (travel, teleconferences, etc.) and expenses associated with outreach to the broader research community. Carefully explain and justify requested support. Administrative support personnel may be budgeted at no more than one full time equivalent (FTE), which may be divided among one or more positions. This FTE must be fully justified.

The CCCR may allocate a minimum of $20,000 and up to $50,000 direct costs each year to the Pilot and Feasibility Program (up to two), which will be administered through the Administrative Core.

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

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for the Administrative Core component.

Specific Aims: Describe the broad long-term objectives to be accomplished by the Administrative Core.

Research Strategy: Please include the following headings:

Leadership

The Core Director and Associate Director of Administrative Core manage the overall CCCR, including the outreach program and the Pilot and Feasibility Program, if proposed. Applicants are encouraged to organize the Research Strategy section of the Administrative Core to align with the CCCR review criteria for the Administrative Core. Define the specific responsibilities of the Core Director and Associate Director with regard to the Administrative Core activities such as the External Advisory Committee, outreach for the CCCR, and the Pilot and Feasibility program, if offered. Additional information on interactions of Administrative Core leadership with Methodologic and Resource Core Directors, institution officials and other involved parties should also be included.

The Administrative Core is expected to identify members, organize and manage the External Advisory Committee to the CCCR. Describe the plans and procedures for nominating and selecting members of this committee. Describe the expected composition of the External Advisory Committee (number of members, types of expertise, etc.), but do NOT name the members of the committee who are not from the CCCR Institution in the application so as not to limit the pool of potential reviewers. The External Advisory Committee should include both users of the Cores and investigators external to the CCCR who may have expertise in the design and management of other core facilities or expertise in the technologies, services, and/or resources offered by the Cores or expertise in the research fields covered by the research community.

Management and Evaluation

The Administrative Core is responsible for coordinating and integrating the CCCR components and activities. Describe the management plans for the CCCR, including fiscal administration, procurement, property and personnel management, planning, budgeting, etc. If the CCCR will involve more than one institution, explain how the management plans will coordinate activities at each of these sites. Describe plans for the management of conflict of interest relating to intellectual property (when applicable).

The External Advisory Committee should be actively involved in the evaluation and planning process of the CCCR. The External Advisory Committee should meet formally at least annually to assist the CCCR Directors in evaluating the scientific progress and optimizing strategies to meet its overall goals for clinical research. The External Advisory Committee will conduct reviews of the Methodologic and any Resource Cores, and be aware of Pilot and Feasibility projects supported by the Administrative Core. The Administrative Core will develop the format for the External Advisory Committee meetings, provide reports on CCCR activities, and provide to the committee members and how the committee may convey comments and recommendations back to the CCCR Directors. Describe how the recommendations from this committee will be incorporated into the planning and management of the CCCR over the course of the award.

If the demand for the services or resources provided through the CCCR exceeds the supply or if a queue is likely to develop, describe criteria for establishing priorities or other strategies for managing supply or demand.

All CCCRs should conduct ongoing evaluation and assessment of activities and whether the CCCR is meeting the goals and expected outcomes and outputs set forth in the grant application. These evaluations should include use of the Cores, the quality of the services and resources provided, and the efficiency by which they are delivered. The Administrative Core should work with the Methodologic and Resource Core Directors to formulate evaluation plans and conduct evaluations of the Resource Cores. The effectiveness of outreach and other enhancement activities in helping the CCCR meet its goals should also be evaluated. The CCCR should monitor current and predict future scientific needs of the research community, and Methodologic and Resource Core activities should adapt to those needs. The External Advisory Committee should be actively involved in this evaluation and planning process. Describe the plans for the Director, Associate Director and Methodologic and Resource Core Directors to meet regularly with this committee. Indicate the format of the meetings; describe any reports on CCCR activities that will be provided to the committee members and how the committee may convey comments and recommendations back to the CCCR leadership. Describe how the recommendations from this committee will be integrated into the planning and management of the CCCR over the course of the award.

Communication

Describe the plans for maintaining effective communication within the CCCR and the plans for communication with the investigators of the research community and other potential users of the Cores. Explain how the communication plans will help to coordinate and integrate the investigators and the activities of the CCCR to promote the CCCR goals.

Outreach Program and Pilot and Feasibility

An outreach program for the CCCR must be proposed. This program should include outreach activities for the Methodologic and Resource Core(s) as well as activities that will serve to expand the research community and/or promote innovative research on the topic of focus of the CCCR. Each CCCR may choose the activities that best suit the needs of the research community, but should justify how the activities fulfill these goals as well as the overall goals of the CCCR. Types of activities that may be part of an outreach program include (and are not limited to) mentoring programs and activities, and support of seminars and visiting scientists. All activities should occur within the context of and/or with the involvement of the Methodologic and Resource Core(s). Innovative approaches to outreach are encouraged. All outreach activities must include a detailed description of Program leadership and management.

Further outreach of the CCCR may be proposed through Pilot and Feasibility studies (mentored, non-mentored, or technology development). Direct funding for these projects may be proposed but descriptions of such projects should NOT be included in the application. Plans for soliciting, reviewing, selecting, managing and reporting on the results of projects during the tenure of the CCCR should be included in the application. Describe the internal institutional plans and procedures to ensure that all projects supported from this award will comply fully with all applicable Federal regulations, policies, and Guidelines, including those for research involving human subjects, including the evaluation of risks and protections in project proposals and appropriate ethical oversight of funded projects. Human Subject and Animal Subject approval dates for Pilot and Feasibility projects (if applicable) should NOT be submitted with the application, but should be provided to NIAMS for approval with Just in Time information, or prior to the start of the pilot project, and with annual progress reports. Otherwise please indicate in the appropriate section that human subjects or vertebrate animals are not involved. A Pilot and Feasibility program should not be used to fund clinical trials.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study
All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type 'Methodologic Core.'

A Methodologic Core is required in a Clinical Research CCCR, but can be defined in multiple ways, and should offer shared resources for clinical research. The Methodologic Core is expected to provide expertise and support to ongoing projects within the research base of the CCCR and to other emerging research opportunities funded elsewhere, including other CCCR investigators that are relevant to the NIAMS mission. These efforts should include but are not limited to methodologic and biostatistics design of clinical projects including maintenance of data integrity and all issues involving patient safety and inclusion.

Other Resource Cores can be included but should be described in the "Resource Core" section of the application. These Cores should be justified by the needs of the research community and appropriate for the focus of the CCCR.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Methodologic Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Methodologic Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Methodologic Core)

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

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

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

Facilities and Other Resources: Describe the physical space available for the proposed Methodologic Core. Document any institutional commitments to provide space or renovate existing facilities. Whenever possible, Resource-based CCCRs are encouraged to enter into cooperative arrangements with established cores in other centers or resource grants offering a similar type of service or resource at the applicant institution.

Equipment: In addition to listing equipment (including location and capabilities) already available for this Resource Core, document any institutional commitments to cost share in equipment.

Other Attachments: The following supportive data table may be included with the Resource Core Component in order to aid in the review of applications. The filename provided for the attachment will be the name used for the bookmark in the application image.

Table of "Use of Resource Cores" may be helpful to describe the projected use of the proposed Core by funded investigators. This table should contain the name of the Resource Core, a list of services and/or other resources offered by the Core, followed by a list of users, their funded projects, and projected usage of each of the services/resources by each project.

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

List all performance sites that apply to the specific component.

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

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

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

Budget (Methodologic Core)

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

Methodologic Core support may include personnel, equipment, services, and facilities. It is important to provide comprehensive budgetary justifications, and to discuss mechanisms for reimbursing Core services.

This grant mechanism is not intended for acquisition of high-cost equipment. Equipment purchases in excess of $25,000 for any year of the grant would require special justification. Under unusual circumstances, where costly items of equipment are requested, the application must document available equipment within the institution and provide clear justification in terms of core service to be provided by the CCCR. Costly items of equipment should be funded through other sources.

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

PHS 398 Research Plan (Methodologic Core)

Introduction to Application: For Resubmission applications (only allowed for the FY2019 due date), an Introduction to Application is allowed in the Methodologic Core component.

Specific Aims: Describe the broad, long-term objectives, and describe concisely the specific aims to be accomplished by the Methodologic Core. Include research to enhance the capabilities of the Methodologic Core, and/or education activities.

Research Strategy:

Describe the background information, needs and gaps that led to the Methodologic Core. How are proposed resources critical for research on the topic of focus of the CCCR? Document that these resources are essential for the research of multiple independently-funded CCCR investigators. What value will be added to the research community by support through the CCCR, beyond that which could be accomplished by a similar level of funding used to purchase services from another source? This is an especially important point to document if the plan is to buy into or combine with an existing institutional core. How the Methodologic Core will enhance the research productivity of investigators in the research community should be described.

Each proposed technique or service should be described in detail. Where applicable, include sections on quality control and data analysis. Whenever possible, generic services (e.g. power calculations, basic biostatistics support, etc.), whether offered by new or existing cores, should be customized to meet the needs of the research community. Provide details of any customization of services that is planned. If resources are provided to investigators at distant sites, describe in detail how this will be accomplished.

The Methodologic Core should be the strongest component of the CCCR and should enhance the value of the resources offered through education on methodologies and other resources offered by the Core, such as consultation on experimental design and data analysis and interpretation. The extent of and approach to this education and consultation should be included.

The organization and proposed mode of operation of the Methodologic Core should be presented. Included should be a plan to prioritize investigator use of the Core as well as a definition of qualified users. Choose this definition carefully, since a goal of the CCCR should be to expand the ranks of investigators engaged in research on the topic of focus of the CCCR and to promote interdisciplinary research. Address how the inclusion of investigators distantly related to the field, which may cause the resources of the Methodologic Core to be spread too thinly, would be handled.

It is expected that the Methodologic Core in CCCRs will receive some reimbursement in the form of modest user fees to offset some of the Core costs. The reimbursement plan should be described. In addition to providing a product or a service, a Core must maintain appropriate quality control. Cores are expected to have an ongoing program that assesses the quality and use of services and resources provided and whether the Core is meeting the needs of the research community. An evaluation plan should be described. Describe how the Methodologic Core will set user fees, taking into account applicable Federal cost principles as discussed in NOT-OD-13-053 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-13-053.html).

Letters of Support: Provide letters of support from outside consultants that will help develop services or provide resources for sharing. Also provide letters of support from potential users of the Methodologic core documenting a sample of the services and resources that would be required by investigators and the potential for specific and direct impact on the research projects from the use of these services and resources. If these documents are included in the "Overall" component, please state so.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type 'Resource Core.'

Additional Resource Cores may be added to the CCCR and defined in multiple ways. The overall purpose of the Resource Core must significantly contribute to the focus of the CCCR and provide innovative support and services to the research community. These Resource Cores may offer shared resources for clinical research to enable CCCR investigators to conduct their independently-funded individual research projects more efficiently and/or more effectively. These Resource Cores should be designed to furnish a group of investigators some service, technique, assay results, or instrumentation in a manner that will enhance the research in progress, utilize human resources more effectively, and improve the quality and cost effectiveness over investigators conducting the same studies without the Resource Core. Alternatively, the Resource Core may provide critical infrastructure to support broad sharing of a unique highly specialized existing resource. All Resource Cores should also attract investigators from other fields to the focus and theme of the CCCR's research by offering specialized services or resources not easily duplicated in an individual laboratory. See Section I. Funding Opportunity Description for some examples.

Resource Cores should be justified by the needs of the research community and should be appropriate for the focus of the CCCR.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Resource Core)

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

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

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

Facilities and Other Resources: Describe the physical space available for the proposed Resource Core. Document any institutional commitments to provide space or renovate existing facilities. Whenever possible, Resource-based CCCRs are encouraged to enter into cooperative arrangements with established cores in other centers or resource grants offering a similar type of service or resource at the applicant institution.

Equipment: In addition to listing equipment (including location and capabilities) already available for this Resource Core, document any institutional commitments to cost share in equipment.

Other Attachments: The following supportive data table may be included with the Resource Core Component in order to aid in the review of applications. The filename provided for the attachment will be the name used for the bookmark in the application image.

Table of "Use of Resource Cores" may be helpful to describe the projected use of the proposed Core by funded investigators. This table should contain the name of the Resource Core, a list of services and/or other resources offered by the Core, followed by a list of users, their funded projects, and projected usage of each of the services/resources by each project.

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

List all performance sites that apply to the specific component.

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

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

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

Budget (Resource Core)

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

Resource Core support may include personnel, equipment, supplies, services, and facilities. It is important to provide comprehensive budgetary justifications, and to discuss mechanisms for reimbursing Core services.

This grant mechanism is not intended for acquisition of high-cost equipment. Equipment purchases by any Resource Core in excess of $25,000 for any year of the grant would require special justification. Under unusual circumstances, where costly items of equipment are requested, the application must document available equipment within the institution and provide clear justification in terms of core service to be provided by the CCCR. Costly items of equipment should be funded through other sources.

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

PHS 398 Research Plan (Resource Core)

Introduction to Application: For Resubmission applications (only allowed for the FY2019 due date), an Introduction to Application is allowed in the Resource Core component.

Specific Aims: Describe the broad, long-term objectives, and describe concisely the specific aims to be accomplished by the Resource Core and how these will enhance clinical research. Include, if proposed, research efforts to enhance the capabilities of the CCCR and/or the CCCR education activities.

Research Strategy: Describe the background information and gaps that led to the proposal of the Resource Core. How are the shared resources critical for research on the topic of focus of the CCCR? Document that these resources are essential for the research of multiple independently-funded CCCR investigators. What value will be added to the clinical research community by support of the Resource Core through the CCCR, beyond that which could be accomplished by a similar level of funding used to purchase such services from another source? This is an especially important point to document if the plan is to buy into an existing institutional core. How the Resource Core will enhance the research productivity of investigators in the clinical research community should be described.

Each proposed technique or service should be described in detail. Where applicable, include sections on quality control and data analysis. Provide details of any customization of services that is planned. For Resource Cores that offer access to a unique resource, the unique resource should be described in a way that emphasizes the effect on clinical research of access to that resource.

All Resource Cores are strongly encouraged to enhance the value of the resources and services they offer through education on methodologies and services offered, as well as consultation on experimental design and data analysis and interpretation. The extent of, and approach to this education and consultation should be included.

The organization and proposed mode of operation of the Resource Core should be presented. Included should be a plan to prioritize investigator use of the Resource Core as well as a definition of qualified users. Choose this definition carefully, since a goal of the CCCR should be to expand the ranks of investigators engaged in research on the topic of focus of the CCCR and to promote interdisciplinary research, while including investigators distantly related to the field or focus of the CCCR may cause the resources of the Resource Core to be spread too thinly.

It is expected that the Resource Cores will receive some reimbursement in the form of fees from core users that will offset some of the costs. The reimbursement plan should be described. In addition to providing a product or a service, a Core must maintain appropriate quality control. Resource Cores are expected to have an ongoing program that assesses the quality and use of services and resources provided and whether the Resource Core is meeting the needs of the research community. An evaluation plan should be described. Describe how the Resource Core will set user fees, taking into account applicable Federal cost principles as discussed in NOT-OD-13-053 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-13-053.html).

Letters of Support: Provide letters of support from outside consultants that will help develop services or provide resources for sharing. Also provide letters of support from potential users of the resources provided by the Resource Core documenting the services and resources that would be used by each investigator and the potential for specific and direct impact on the research projects using those services and resources. If these documents are included in the "Overall" component, please state so.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: https://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization's profile in the eRA Commons and for the System for Award Management (SAM). 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 our Post Submission Application Materials policy.

Important Update: See NOT-OD-18-228 for updated inclusion and human subjects review language for due dates on or after January 25, 2019.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement: After the review of the individual components of the application, an overall impact score will be assigned to the application. This score will reflect not only the quality of the individual cores and administration, but also how the proposed CCCR will bring together all these elements in a functional and cohesive unit. The overall score may be higher or lower than the "average" of the descriptors based on the assessment of whether the "whole is greater than the sum of its parts."

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CCCR 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 CCCR proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Does the CCCR address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the CCCR are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA

What is the significance to research in the NIAMS mission area of providing these resources to the proposed research community? What is the likelihood that the shared resources and new environment of the CCCR will lead to major clinical advances in the field? Will the proposed CCCR enable clinical investigators to conduct their research more efficiently and effectively? Are the CCCR resources likely to accelerate progress beyond what can be achieved through access to already supported centralized resources? Are there synergy and integration within the CCCR? Does the CCCR address the most pressing needs of the NIAMS clinical research community?

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

Specific to this FOA

Do the Director and Associate Director have the leadership and research qualification to lead a CCCR? Is there a substantial productive and funded research base or are there unique offerings/resources associated with the CCCR to provide sufficient usage?

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?

Specific to this FOA

Are there plans to develop new and/or unique state-of-the-art clinical core services during the tenure of the CCCR? Will the services and resources provided by the CCCR evolve with the science conducted by the research community investigators? For the CCCR that may, by its nature, not be highly innovative, are the contributions essential to advance the field?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the CCCR? 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 CCCRinvolves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA

Are there effective Leadership, Management and Evaluation, and Communication plans? Is the Outreach Program designed to effectively expand the research community in the area of focus of the CCCR? Is it likely that there will be coordination, collaboration and synergy among the Methodologic Core, optional Resource Core components, Administrative Core component and existing research community? Does support for the Methodologic and Resource Cores from the CCCR provide added value beyond that which would be provided through a fee for service or access, especially where support is proposed for an existing resource? Are the Core(s) cost-effective in providing services and resources to the CCCR Investigators? Do the Core(s) effectively leverage existing resources at this or another institution?

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 CCCR benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA

Is there evidence of sufficient institutional commitment to the CCCR? Does the application define a productive, high quality and adequately funded (with federal, state, and private peer-reviewed funding awards) research community that needs the services and resources proposed by the CCCR? Are the identified Investigators well defined in terms of their relationship to the CCCR, and are their letters of support for the application adequate to suggest that the CCCR resources will be fully utilized? Is the research community sufficiently broad to foster new research and to promote collaborations? Does the proposed CCCR utilize available resources well? Where support by the CCCR for existing institutional scientific resources is proposed, does that resource provide a range of services or efficiency that would not otherwise be available to members of the CCCR? If there will be a connection with an NIH funded CTSA, is the collaboration well described and is there an adequate letter of agreement from the CTSA Program Director(s)/Principal Investigator(s)?

Reviewers will consider the following criteria in the determination of an overall impact score for the Administrative Core, although scores for the individual criterion will not be provided.

Purpose

Is the proposed Administrative Core well matched to the needs of the overall CCCR?

Scientific Oversight

Is the management proposed appropriate for scientific administration as well as fiscal administration, procurement, property and personnel management, planning, budgeting, etc.?

Leadership

Do the CCCR Director and Associate Director have the leadership and research qualifications to lead a CCCR? Have the Director and Associate Director proposed adequate time commitment to effectively manage the CCCR? Do the proposed CCCR Director and Associate Director have the collective expertise and leadership to identify and focus research projects on clinically relevant issues? Are appropriate and well-defined responsibilities described for the Director and Associate Director, External Advisory Committee, Resource Core Directors, institution officials and other involved parties? Have the scientific and administrative leadership committed adequate time and effort for the effective management of the CCCR program? Are there adequate plans for establishing the External Advisory Committee and for the Director and Associate Director to communicate regularly with the committee? Are the composition and plans for selecting the members of the committee appropriate?

Management and Evaluation

Is the management plan appropriate for fiscal administration, procurement, property and personnel management, planning, budgeting, etc.? Are the individual budgets appropriate for the proposed work to be done in Methodologic and Resource Core(s), for an Outreach program, for any proposed Pilot and Feasibility program, and for any other proposed programs in relation to the total CCCR? Are there adequate plans for objectively evaluating the functioning of the CCCR by the Director and Associate Director, with input from the External Advisory Committee? How will the recommendations of the External Advisory Committee be integrated into the effective fiscal, personnel and scientific management of the CCCR over the course of the grant award?

Communication

Are there adequate plans for the establishment and maintenance of effective internal communication and cooperation among the CCCR investigators, Core personnel, leadership of the CCCR, and the External Advisory Committee? If the CCCR will involve multiple sites or institutions, is there a detailed plan of the communication strategies aimed to integrate the distant components and investigators into a coordinated entity? Will communication and outreach through the Outreach and/or Pilot and Feasibility Programs reach all of the research community investigators as well as investigators beyond the CCCR in order to promote expansion of the pool of users of the Core facilities for research on the topic of focus of the CCCR?

Outreach and Pilot and Feasibility Programs

Is there a well-designed and innovative plan for activities that are likely to enhance the communication, coordination and collaboration among research community investigators and to expand the pool of investigators and broaden the spectrum of research on the topic of focus of the CCCR conducted through the CCCR? If proposed, does the Pilot and Feasibility program support the goals of this FOA by representing an initial proof-of-concept and/or contributing to the robust premise of the clinical research? Are there adequate institutional plans and procedures to assure compliance with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

Environment

Is the environment for the Administrative Core adequate and appropriate to support the overall CCCR as proposed? Is there evidence of institutional support for the management of CCCR?

Reviewers will consider the following criteria in the determination of an overall impact score for the Methodologic Core, although scores for the individual criterion will not be provided.

Purpose

Is the proposed Methodologic Core well matched to the needs of the overall CCCR?

Significance

Does the Methodologic Core provide services and/or resources well matched to the scientific needs of the research community? Are unique services offered? If these services duplicate or overlap with existing institutional resources, how will this be addressed? Will the Core be used by multiple investigators? What is the likelihood that the Resource Core will increase efficiency, accelerate progress and promote new research directions and meaningful collaborations among research community investigators? Is the process for maintenance of data integrity and assistance with development of safety plans for the projects supported by the CCCR adequately addressed? Is there evidence that the Methodologic Core can and will support clinical research projects in more than one chronic disease or condition of interest to the NIAMS?

Investigator(s)

Are the qualifications, experience, and commitment of the leader of the Methodologic Core and other key personnel adequate and appropriate for providing the proposed services?

Innovation

Are there plans to develop and establish unique state-of-the-art core services for clinical research and clinical trials during the tenure of the CCCR? Will efforts be made to development and/or adaptation of emerging methodologies to meet the needs of the clinical research community? Will the services and resources provided by the Methodologic Core not only evolve with the clinical research conducted by the CCCR Investigators but will these services and resources be developed to drive the clinical approaches with increasingly sophisticated and powerful technologies? Is the Methodologic Core likely to promote interdisciplinary research?

Approach

Are the services and resources of the Methodologic Core of high quality and unique to the needs of the CCCR? Does support for the service or resource through the CCCR provide added value beyond that which would be provided through a fee for service or access, especially where support is proposed for an existing resource? What is the overall quality of the proposed core services? Are adequate quality control processes proposed for the services provided by the Methodologic Core (including procedures, techniques, and quality control)? What are the criteria for prioritization and usage of Core products and/or services? Is the Methodologic Core cost-effective in providing services and resources to the research community investigators? Is cost reimbursement adequately addressed? Do the Resource Cores effectively leverage existing resources at this or another institution? Does the methodologic core propose an adequate plan for enhancing the clinical training environment at the CCCR? Will the core provide opportunities such as webinars, online courses, or other computer based training to enhance the capabilities of faculty, staff, students and fellows associated with the CCCR to conduct clinical research using a wide range of approaches?

Environment

Is the environment for the Methodologic Core adequate and appropriate to support the CCCR as proposed? Are the physical space, facilities and equipment adequate and appropriate? Is there evidence of institutional support or commitment?

Reviewers will consider the following criteria in the determination of an overall impact score for any Optional Resource Core(s), although scores for the individual criterion will not be provided.

Purpose

Is the proposed Resource Core well matched to the needs of the overall program? Do the services offered best fit within a core structure? If this is an add-on to a preexisting core, what is the benefit to the CCCR over direct purchase of services from the existing core?

Significance

Does the Resource Core provide services and/or resources to meet the scientific needs of the research community? Will the Core provide a unique and necessary component to enhance existing or stimulate new clinical research? What is the likelihood that the Resource Core will increase efficiency, accelerate progress and promote new research directions and meaningful collaborations among community of clinical investigators?

Investigators

Are the qualifications, experience, and commitment of the Resource Core Director and his/her collaborations with CCCR investigators appropriate to the proposed clinical area and/or shared resource? Are other key personnel adequate and appropriate for providing the proposed facilities or services?

Innovation

Are there plans to develop new and/or unique state-of-the-art core services during the tenure of the CCCR through technology development and/or adaptation of technologies to meet the needs of the clinical research community? Will the services and resources provided by the Resource Core not only evolve with the science conducted by the CCCR Investigators, but are they also likely to drive the science with increasingly sophisticated and powerful technologies? Is the Resource Core likely to promote interdisciplinary research? For a Resource Core that by its nature is not innovative, is it essential to advance clinical research in the field?

Approach

Are the services and resources of the Resource Core of high quality? Does support for the service or resource through the CCCR provide added value beyond that which would be provided through a fee for service or access, especially where support is proposed for an existing resource? Are there procedures for quality control of the services and resources for each Core? Is the Resource Core cost-effective in providing services and resources to the research community investigators? Do the Resource Cores effectively leverage existing resources at this or another institution? What is the overall quality of the proposed core services?

Environment

What is the overall quality of the environment for the Resource Core? Is there adequate institutional commitment to the CCCR, including physical space, if required, for the Resource Core? Are there lines of accountability regarding management of the Resource Core and commitment from the CCCR to the individuals responsible for conducting essential core functions?

As applicable for the CCCR 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.

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

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

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

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.

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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the Cores.

Not Applicable

Not Applicable

As applicable for the CCCR 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.

Not Applicable

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

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.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by 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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC). 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.

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

If Pilot and Feasibility projects are included in the CCCR Outreach program, a complete project application (including biographical sketches, personnel and budget justification, research plan, human and/or animal subject sections and any IACUC, IRB or other required documentation), and the critiques of the proposals by the Advisory Committee must be provided to NIAMS with the Just in Time information or prior to the start of the Pilot and Feasibility projects. Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH's Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant's integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 "Federal awarding agency review of risk posed by applicants." This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Telephone: 301-945-7573

Xincheng Zheng, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-4953
Email: xincheng.zheng@nih.gov

James Witter, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: witterj@mail.nih.gov

Kathy Salaita, Sc.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: witterj@mail.nih.gov

Steve Austin
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-3504
Email: austins2@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.