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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

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.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
  • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Vicky Whittemore, PhD
Telephone: 301-496-1917
Fax: 301-402-1501
Email: [email protected]

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in 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: 1 required
• Administrative Core: 1 required; maximum of 1
• Research and/or Clinical Core: optional; maximum of 2
• Projects: minimum of 2; maximum of 3

Overall Component

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

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall)

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

Budget (Overall)

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.

PHS 398 Research Plan (Overall)

Specific Aims: Describe the overall aims of the proposed ME/CFS CRC.

Research Strategy:

The Overall section should state the vision and rationale for the proposed ME/CFS CRC, and provide an overview of planned synergistic activities within the ME/CFS CRC and a proposed process for the solicitation, submission, review and support of pilot projects. Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Provide a vision statement for the ME/CFS CRC, including expected contributions to the advancement of ME/CFS research and/or treatment. Describe how the CRC addresses an important problem or a critical barrier to progress in ME/CFS research. Include the overall ME/CFS Center program objectives or the proposed grant period. Describe the proposed interdisciplinary approach, including the potential contribution the ME/CFS CRC can make as a local resource for and national leader in ME/CFS research and to effectively and rapidly advance an innovative, interdisciplinary, highly impactful research program. Describe and clearly justify the specific ME/CFS research need(s) to be addressed and the scientific premise for the proposed studies. Describe how successful completion of the aims will change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field. A plan for community outreach and engagement with other ME/CFS stakeholders (patients, advocacy organizations, etc.) should be described.

Describe the relevant group experience and expertise of the PD(s)/PI(s), collaborators and researchers as a whole without duplicating information in the biosketches. Describe the complementary and integrated expertise of the PD(s)/PI(s) and other investigators, as well as their leadership approach and governance plan, as well as the organizational structure of the ME/CFS CRC.

Innovation: Describe how novel approaches, investigator expertise, and collaborative activities will advance the goals of the ME/CFS CRC program, including unique contributions that will elucidate the causes of and result in potential therapeutic advances for ME/CFS. Describe how the proposed research will challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions. Describe how the proposed research will utilize novel approaches to advance our understanding of ME/CFS and make major advances in the field, including leading to future development of novel and/or improved therapies for ME/CFS.

Approach: Describe the general research framework of the ME/CFS CRC including the overall strategy, methodology, and analyses to be used to accomplish the aims of the projects. Discuss the proposed research program, highlighting its central theme. Describe the synergy among the ME/CFS CRC components, especially the scientific and collaborative approaches that will ensure thematic coherence of the ME/CFS CRC research and activities. Describe the strategies that will be utilized to ensure a robust and unbiased approach, including potential problems, alternative strategies, and benchmarks for success. Identify the proposed research that may be in the early stages of development that may be risky, and how the risk will be managed. Describe plans to address weaknesses in the rigor of the prior research that serves as the key support for the proposed project. Describe the experimental design and methods proposed and how they will achieve robust, rigorous and unbiased results. Applicants to the program should describe and discuss (as appropriate to the proposed studies) the rationale for the chosen model(s) and endpoints, adequacy of controls, route and timing of therapeutic dosing, justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results. These criteria should also be addressed when describing supporting data (if presented) and in the design of the proposed studies within the Research Strategy section (as appropriate).

Detailed descriptions of preliminary data for new projects should be included within the relevant Research Project section, not in the Overview.

Provide summary evidence for feasibility, including preliminary findings that support the proposed research in the ME/CFS CRC. Present compelling evidence that the assembled research team will work together effectively to accomplish the goals of the proposed ME/CFS CRC, and will collaborate with other ME/CFS CRCs and the DMCC to advance research in ME/CFS. Describe potential to serve as a local resource for and national leader in ME/CFS research.

Letters of Support:

Include a letter from a high-level institution official(s) (e.g., Dean of the School of Medicine, Vice President for Research) to confirm institutional commitment to the ME/CFS CRC program. The letter should provide details on how institutional commitment will be established, examples of how the institution maintains and promotes scientific excellence in ME/CFS research, and how the ME/CFS CRC will be prioritized within the institution (relative to other NIH and non-NIH funded programs). Examples of institutional commitment may include, but are not limited to: provision of discretionary resources to the ME/CFS CRC Director, funding for pilot projects, support for recruitment of scientific talent and career enhancement activities, access to institutional infrastructure assignment of specialized research space, funding and resources for community outreach and engagement activities, and or other means of support. The letter should describe the role of the institution in conflict arbitration and resolution, should such arise among ME/CFS CRC investigators.

The letter should describe collaborative efforts and/or opportunities with other institutional programs. For example, opportunities may exist for collaboration with the Clinical and Translational Science Awards (CTSA), a consortium of NIH-funded academic health centers that accelerate the process of translational laboratory discoveries into treatments for patients, train a new generation of clinical and translational researchers, and engage communities in clinical research efforts. The letter should describe how the CRC may leverage additional institutional partnership opportunities to further program goals.

Applicant institutions receiving funding from other ME/CFS-related research, should detail the unique contributions of the ME/CFS CRC to the institutional ME/CFS research effort, how interaction among these projects will advance ME/CFS research, and provide commitment to the support of the ME/CFS CRC in this context.

Collaboration with Non-governmental Organizations (if applicable): ME/CFS CRCs and non-governmental patient advocacy organizations have common goals for understanding the cause(s) of ME/CFS and to improve treatment. Letters should detail planned or ongoing outreach and partnership activities between ME/CFS CRCs and these groups.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Resource Sharing Plan (that includes a data sharing plan).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

Utilization of extant biospecimens (if applicable):letters of support or approval for use of those samples, included those banked at BioSEND, must be included. If selected BioSEND samples include those adjudicated by the NINDS Biospecimen Review Access Committee (BRAC), a letter indicating BRAC approval must be included. Contact [email protected] for additional information on biospecimen request procedures for NINDS cohorts including the Chronic Fatigue Initiative Cohort.

NINDS Human Cell and Data Repository(NHCDR, if applicable):applicants proposing to collect human cell sources (i.e. fibroblasts, peripheral blood mononuclear cells) for induced pluripotent stem cell (IPSC) line derivation should include a letter of support from the NHCDR, including detailed plan and timeline for related line derivation and deposition. [email protected] for additional information.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type ‘Insert Name.’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

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

Budget (Administrative Core)

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

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

PHS 398 Research Plan (Administrative Core)

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

Specific Aims:

For Cores (Administrative or Research Cores), describe the goals and planned activities of the Core, as well as its essential relationship to the Aims of at least two Research Projects.

For Projects, state the research goals of the research project and expected contributions to the goals of the ME/CFS CRC. Explain why the ME/CFS CRC structure is required to accomplish the proposed aims. Address how successful completion of the proposed studies will inform and advance future ME/CFS research and clinical trials.

Research Strategy:

Administrative Core

For the Administrative Core, organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe how the Administrative Core will serve as the organizational foundation for research activities of the ME/CFS CRC, as well as how the Core will effectively support the ME/CFS CRC to serve as a local and national resource for ME/CFS research.

Innovation: Describe how the Administrative Core will maximize synergy among ME/CFS CRC investigators, and fosters relationships with broader research and advocacy communities.

Approach: Describe the proposed activities of the Core, including but not limited to the following:

Promote the integration and function of the ME/CFS CRC components and activities.

Provide support for the ME/CFS CRC Director in oversight of the CRC governance.

Organize regular meetings of the ME/CFS CRC Executive Committee (composed of the ME/CFS CRC Director, project and core Leads and the ME/CFS CRC Administrator).

Develop and execute timely community outreach and engagement activities.

Coordinate career enhancement activities within the ME/CFS CRC.

Coordinate participation of the investigators associated with the ME/CFS CRC in the annual ME/CFS CRC Directors' and the Steering Committee Meeting (organized by the DMCC).

Coordinate and maintain an accounting of resource generation, sharing of data, biospecimens and resources with the DMCC and related utilization, and steps taken to maximize the research utilization of these resources within and beyond the ME/CFS CRC.

Provide advance notice of manuscripts and publications to the NIH Project Scientist; work with the appropriate NIH Office of Communications on press releases highlighting the ME/CFS CRC accomplishments.

Work with the PD/PI to prepare and submit annual progress reports.

Work with the PD/PI to provide assurance for compliance with NIH policy requirements.

Provide timely updates to ME/CFS CRC information to the DMCC in order to keep the overall and specific ME/CFS CRC websites updated.

The Approach section should include plans for the following:

Administrative Structure:

Describe the administrative structure of the ME/CFS CRC, including lines of communication, decision-making processes, and procedures for resolving conflicts. Describe the administrative, technical, and scientific responsibilities for ME/CFS CRC personnel and collaborators.

ME/CFS CRC Governance: Describe plans to convene an internal Executive Committee, consisting of the ME/CFS CRC Director, Administrator, Project Leaders and Core Leaders, to assist the Director with scientific and administrative decisions. Describe Executive Committee activities, including regular meetings to discuss Center activities and research priorities. Describe inclusion of institutional officials. Describe conflict resolution strategies.

Pilot Projects

Describe the process by which proposals for pilot projects will be solicited, reviewed, and selected. Potential projects should not be proposed.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Research Core

When preparing your application in ASSIST, use Component Type ‘Core’.

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

SF424 (R&R) Cover (Research Core)

Complete only the following fields:

• Applicant Information

• Type of Applicant (optional)

• Descriptive Title of Applicant’s Core

• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Core)

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

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

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

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

In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Lead’ and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Core personnel responsible for data management and data sharing should be identified in the application.

Budget (Research Core)

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

Budgeting of funds to collect and store biospecimens from study participants, including postmortem tissues, for direct use in ME/CFS CRC research projects is permitted, but the NIH will not provide funds to support infrastructure for general brain or biospecimen banking.  All biospecimens should be stored and shared through the NeuroBioBank (NeuroBioBank), NINDS-supported Coriell Institute - NINDS Human Genetics Repository, or other existing biorepositories as approved by NIH.  For the NINDS Policy on support for related efforts, see:  Notice of Change in Funding Mechanisms for Brain Banks and Biospecimen repository policies (NOT-MH-12-020).

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

PHS 398 Research Plan (Research Core)

Specific Aims:   Describe the goals and planned activities of the Research Core, as well as its essential relationship to the Aims of at least two Research Projects.    

Research Strategy:  Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe the essential relationship of the Research Core to at least two proposed research projects, the means through which this Core will advance the aims of each associated project, and what resources generated will support the ME/CFS CRC's status as a local and national resource for ME/CFS research.

Innovation: Describe how the standardized approaches and facilities utilized will both address the theme of the ME/CFS CRC and advance ME/CFS research.

Approach: Indicate percent usage by each proposed research project.

Research Core approaches may include, but are not limited to:

• Shared, standardized assays
• Neuropathology
• Genetics/genomics
• Computational modeling
• Proteomics, metabolomics, microbiome

Research Core approaches cannot include the following:

• Hypothesis- or discovery-driven aims
• Method or tool development

Use of ME/CFS CRC Research Cores to establish and maintain institutional infrastructure and generalized resources is beyond the scope of this FOA; a companion FOA (RFA-NS-22-020) has been issued and should be utilized for those purposes.

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. A Resource Sharing Plan is expected with plans for sharing resources with the ME/CFS DMCC (see companion RFA-NS-22-020).

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.   

PHS Human Subjects and Clinical Trials Information (Research Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Projects

When preparing your application in ASSIST, use Component Type ‘Project’.

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

SF424 (R&R) Cover (Project)

• Complete only the following fields:
• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Basic Research Project)

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

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

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

Project /Performance Site Location(s) (Project)

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 (Project)

In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Project)

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

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

PHS 398 Research Plan (Project)

Specific Aims:  State the aims of the basic research project and the hypothesis to be tested.

Research Strategy:  Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe the rationale for proposed clinical studies based on unmet medical need for ME/CFS. Describe and clearly justify the identified research need.

Innovation: Describe novel aspects of clinical studies and potential to inform disease mechanisms and advance state-of-the-art treatment strategies for ME/CFS.

Approach: Describe how the proposed project will improve understanding and treatment of ME/CFS. State the biological rationale for the intended approach, including supporting data from rigorously designed preclinical experiments and clinical studies. Indicate the methodological rigor of proposed studies. Provide the rationale for the chosen study participants and endpoints, adequacy of controls, justification of sample size, statistical methods, and robustness and reproducibility of results.

Letters of Support: Letters of support from collaborators and consultants should be included as appropriate.

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 and Biospecimen Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Project)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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.

Common Data Elements (CDEs)

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

In order to maximize data standardization across studies, the NIH strongly encourages researchers to use the Common Data Elements ME/CFS CRC clinical research projects and cores will be encouraged to include General CDEs and ME/CFS CDEs.

General CDEs

All "core" general CDE items and forms will be required in the following domains for all study participants:

Participant/Subject Characteristics (Demographics)

Participant/Subject History (Medical History and Behavioral History)

Assessments and Examinations (Physical/Neurological Exam, Vital Signs, Laboratory Tests and Biospecimens/Biomarkers)

Treatment/Intervention Data (Prior and Concomitant Medications and Supplements)

Protocol Experience (Inclusion and Exclusion Criteria, Informed Consent and Enrollment)

Applicants may also employ supplementary assessment and measurement tools if relevant to addressing the specific hypotheses proposed in their application. If other tools are proposed, applicants are strongly encouraged to use those suggested or provided by the CDE program.

As appropriate, applicants are encouraged to make use of the following resources for clinical research:

- NeuroQOL (http://www.neuroqol.org)

- NIH Toolbox (http://www.nihtoolbox.org)

- PROMIS (http://www.nihpromis.org)

Leveraging Existing Research Resources

Applicants are strongly encouraged to leverage existing NINDS research resources for their studies whenever possible. Such resources may include biospecimens from NINDS BioSEND repository or other cell and tissue repositories, such as the NINDS Human Cell and Data Repository (NHCDR) and the NIH NeuroBioBank, all of which bank biospecimens, cells and tissue.. Leveraging the resources and support from advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program are also encouraged. Studies are also encouraged that leverage the resources of ongoing clinical trials supported through other Federal or private funds.

Clinical biospecimen collection

Applications proposing to collect biospecimens are strongly recommended to use the NINDS BioSpecimen Exchange for Neurological Disorders (BioSEND) repository includingprotocols and procedures, and all specimens collected and banked with BioSEND must come from individuals who have consented to banking and sharing broadly with academia and industry and must be consistent with NINDS BioSEND recommended consent language.

IMPORTANT: costs for biospecimen collection are not included as a component of the NINDS BioSEND repository award. Therefore, most costs for the biospecimen banking are borne by the grantees utilizing this resource (see NOT-NS-15-046). Applicants planning projects in which biospecimens will be collected are strongly advised to consult with NINDS Biomarkers Repository staff to obtain a quote for biospecimen banking costs (email: [email protected]).

Similarly, applicants should contact the NINDS Human Cell and Data Repository (NHCDR) for a quote to obtain support for collection of human source cells (fibroblasts, peripheral blood mononuclear cells, PBMC) and derivation of iPSC lines (email: [email protected]).

Post Submission Materials

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

Section V. Application Review Information

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

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

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

Does the ME/CFS CRC 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 ME/CFS CRC 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?

Does the proposed ME/CFS CRC identify and address a critical challenge in ME/CFS research? Is there strong evidence that the proposed ME/CFS CRC will advance research in ME/CFS, through both its scientific projects and cores? Will the proposed Center effectively and rapidly advance an innovative, interdisciplinary, highly impactful research program while serving as a national leader in ME/CFS research? Is the use of the Cooperative Agreement (U54) mechanism justified and will the proposed research benefit from the ME/CFS CRC structure?

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

Investigator(s)

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

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the ME/CFS CRC? If Early Stage Investigators or New Investigators, or 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?

Reviewers will consider the following during evaluation of the ME/CFS CRC Director:

Will the ME/CFS CRC Director provide visionary scientific leadership?

Does the Director have appropriate leadership experience, including leading a large-scale research program that predicts success of the ME/CFS CRC?

Is the Director an established leader in scientific research with a history of successful funding, as well as currently active funding?

Has the Director made an appropriate time commitment to the ME/CFS CRC, including leadership of the Administrative Core?

If the Director’s primary area of expertise is in an area other than ME/CFS research, is it clear that the Director’s skills can be applied in novel ways to the advancement of ME/CFS research and treatment?

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

Innovation

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

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?

During evaluation of the proposed ME/CFS CRC applications, reviewers will consider the level of innovation specifically related to state-of-the-art ME/CFS research, including the following: Does the ME/CFS CRC take novel approaches to advancing the stated goals of the proposed ME/CFS CRC, i.e., will proposed research advance understanding of ME/CFS and have potential to lead to the development of novel and/or improved therapies? Are the proposed projects likely to make major rather than incremental advances toward this goal?

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

Approach

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

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

Is the ME/CFS CRC organized around a clearly articulated central theme? Is the synergistic relationship among the ME/CFS CRC components, especially the scientific and collaborative approaches that will ensure thematic coherence of the research and activities, clearly described? Will successful completion of proposed objectives directly inform the pathology, progression and treatment of ME/CFS? Is there evidence that individual investigators will function as an effective collaborative team to achieve the goals of the ME/CFS CRC? Does the ME/CFS CRC have the capacity to mobilize local resources and contribute to ME/CFS research at a local and national level?

Are there appropriate plans for the ME/CFS CRC to collaborate and otherwise contribute to the overall ME/CFS CRC program (the Network), the ME/CFS CRC Steering Committee, the annual ME/CFS CRC Directors' meeting, and other program-wide activities?

Reviewers should address whether the application adequately adresses the rationale for the chosen model(s) and endpoints, adequacy of controls, route and timing of therapeutic dosing , justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results as are appropriate to the proposed studies.

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

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

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

In addition, reviewers will consider the following:

Is there reasonable evidence that the institution will provide support for the ME/CFS CRC, e.g. by provision of discretionary resources to the ME/CFS CRC Director, recruitment of scientific talent, funding for pilot projects, assignment of specialized research space, access to/use of resources, and/or by any other means?

Does the applicant institution support a strong research base on ME/CFS and/or similar diseases? If the applicant institution houses other large-scale, ME/CFS-related research efforts, is there adequate description of the relationship between the proposed ME/CFS CRC and those projects, and is potential overlap addressed appropriately?

If ME/CFS CRC investigators are located at more than one institution, are planned communication and collaboration strategies detailed and appropriate?

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

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

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

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

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

Review Criteria - Cores

Reviewers will provide overall numeric scores; individual criterion scores are not provided. The review criteria for the individual cores are provided below.

Administrative Core

Does the Administrative Core Lead/ME/CFS CRC Director have appropriate expertise and dedicate sufficient time to administrative activities? If an Associate Director is named, does that person have required expertise to effectively assist the Center Director with scientific and administrative management? Does the ME/CFS CRC Administrator have sufficient expertise with NIH policies, practices and fiscal management to provide support for the program?

Is the line of communication clear between the ME/CFS Director and Administrator? Is there an appropriate plan for establishing and maintaining effective communications and cooperation among the ME/CFS CRC investigators and with investigators outside the CRC? Is the proposed management structure appropriate for scientific administration, coordination of resource generation and utilization, as well as fiscal administration, procurement, property and personnel management, planning and budgeting? Does the Core support the ME/CFS CRC's role as a national leader in ME/CFS research?

Are there internal and external procedures for monitoring and evaluating the proposed research projects and core facilities/resources? Are there appropriate plans for management of data, animal models and other resources?

Are proposed career enhancement activities well-integrated into the theme of the ME/CFS CRC? Are proposed career enhancement activities specifically designed for ME/CFS CRC investigators, i.e. are activities separate from and do they enhance/build upon existing institutional resources and programs? Is there a clear strategy for the organization of outreach activities? Are proposed outreach and partnership activities designed to inform and engage the public about research ongoing in the ME/CFS CRC, as well as how that research integrates into current advances in ME/CFS research? Do ME/CFS CRC investigators describe a plan for community outreach and engagement activities?

Is the method for soliciting, reviewing, and selecting pilot projects appropriately described?

Research Cores

Is the Research Core essential to advance the scientific aims of at least two proposed research projects? Does the Core address the central theme of the overall program? Will the facilities or services provided by the Core (including procedures, techniques, and quality control) be used effectively? Are the Core Lead and key personnel well-qualified to provide the Core service(s)? Does the Core have the potential to generate and share resources that support the Center's status as a national resource for ME/CFS research?

Study Timeline

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

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

Reviewers will also comment on the plan for sharing of biospecimens with NIH-supported biospecimen repositories.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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

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

Applications will be assigned 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. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDSC) Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. 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.

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

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

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

Prior Approval of Pilot Projects

Recipient-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 recipient institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The recipient 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: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution's specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
 

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

• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Coordinating the meetings of the Steering Committee that will be comprised of the key personnel for the project.

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

The NINDS Project Coordinator will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards. The Project Coordinator, with no role in stewardship of the award, will provide technical assistance, advice, coordination, and other program actions to support the recipients of the cooperative agreement during the conduct of an activity. In addition to the Project Coordinator, a Program Officer (PO) will be responsible for normal program stewardship of awards and will sign off on the grant documents and be responsible for the stewardship of the award, including approving the milestones. The PO is named in the award notice.

Other officials who can be advisory to the PO are:

• The Project Team (PT), which is a group of NIH staff including subject matter experts (SMEs), that reviews and advises the PO on progress towards milestones and timeline but does not collaborate scientifically with the PI and does not have signing authority. The members are not listed on the Notice of Award.
• An established oversight committee that will review proposed milestones and milestone progress reports from all the teams and provide feedback to the NIH. The Program Official will determine whether members of this committee have any connections to the projects that might constitute a COI. Members will be required to recuse themselves from reviews of any project for which they have a real or perceived COI.
• The Program Official will approve final project milestone language based on feedback from the oversight committee and other NIH staff as is needed and appropriate.

Areas of Joint Responsibility include:

• None; all responsibilities are divided between recipients and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 75and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Vicky Whittemore, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917 Email: [email protected]

Cheryl Mcdonald
National Heart, Lung, And Blood Institute (NHLBI)
Phone: 301-435-0545
E-mail: [email protected]

Inna Belfer, MD, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-435-1573
Email: [email protected]

Joseph J. Breen, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4123
E-mail: [email protected]

Center for Scientific Review (CSR)
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]  

Leslye Fulwider
National Heart, Lung, And Blood Institute (NHLBI)
Phone: 301-480-9544
E-mail: [email protected]

Shelley Headley
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Yescenia Mendoza
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3671
E-mail: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.