It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

New applications (U24) are invited for the ME/CFS CRC Data Management and Coordinating Center (DMCC). In a companion FOA, the Trans-NIH Working Group also invites new applications (U54) for ME/CFS CRCs. The purpose of the DMCC is to facilitate and support basic and clinical research in the ME/CFS CRCs through 1) data management for data mining, sharing and analysis across the ME/CFS CRCs; and 2) coordination of activities across the ME/CFS CRCs and in the outreach and partnership activities planned by the CRCs.

The ME/CFS CRCs working with the DMCC will perform collaborative multi-site clinical research on ME/CFS within each CRC and across the CRCs. The ME/CFS CRCs and DMCC will work together to standardize study protocols and data collection clinical studies. Biostatisticians from the ME/CFS CRCs and DMCC will provide statistical support for protocol development and assist in study design and analysis. The DMCC will provide the data management infrastructure and support necessary for the ME/CFS CRCs to function optimally. The DMCC will work with the ME/CFS CRCs to integrate and coordinate protocols, forms, research tools and IRB approval for the studies carried out in the ME/CFS CRCs.

Background

The ME/CFS CRCs will partner with a single Data Management and Coordinating Center (DMCC). This initiative will support a collaborative and coordinated network comprised of investigators at multiple institutions/sites and patient advocacy groups committed to investigation of ME/CFS working in partnership to enhance communication and sharing of resources in a multidisciplinary approach. The DMCC together with the ME/CFS CRCs supports a comprehensive and integrated approach to data collection, storage, and management, and the integration of clinical data with other unique data, including, but not limited to genetic, imaging, pathologic, and laboratory data. This DMCC will serve the needs of the ME/CFS CRCs while striving to incorporate new approaches and technologies to increase efficiencies while lowering costs.

The ME/CFS CRCs (established under RFA-NS-17-021) will each consist of a group of multidisciplinary basic and clinical investigators, multiple institutions, and relevant organizations, including patient advocacy groups and will focus on areas of ME/CFS that are relevant to the interests of the participating NIH Institutes and Centers (ICs). The DMCC will serve as a resource, working with and providing expertise for the ME/CFS CRCs. It will provide a scalable coordinated clinical data integration of developed and publicly available datasets for data mining in the ME/CFS CRCs, web-based recruitment and referral, and a user-friendly resource site for the public. The DMCC will provide a management system for collection, storage, as well as a portal and tools for research scientists and clinicians. In addition, the DMCC, in conjunction with the NIH, will provide logistical and administrative assistance for ME/CFS CRC activities; produce and/or maintain Operating Policy and Procedures for the ME/CFS CRCs, documents, worksheets, and data collection forms; and monitor compliance while addressing privacy and confidentiality issues related to database management, and multi-level data sharing. The ME/CFS CRCs will be expected to collaborate with the DMCC throughout the course of the studies in order to assure compatibility and standardization of data management approaches.

Organization of the ME/CFS CRCs and DMCC

The ME/CFS CRCs and DMCC will form a cooperative group composed of the ME/CFS CRC investigators and patient advocates and a single DMCC to facilitate research in ME/CFS carried out by the ME/CFS CRCs. A Steering Committee, composed at a minimum of the PD/PI (Director) of each ME/CFS CRC, the PD/PI (Director) of the DMCC, representatives of the patient advocacy groups, and the Administrator for each ME/CFS CRC will establish the procedures for the function of the ME/CFS CRCs, as outlined in section "Steering Committee."

The ME/CFS CRCs and DMCC will require cooperation among the Administrators for each ME/CFS CRC, the Director of each ME/CFS CRC and their collaborators, the Director of the DMCC, and the participating NIH IC Project Scientists to maximize their effectiveness.

The DMCC will develop and make available a secure, customizable coordinated clinical data management system for collection, storage, and analysis of diverse data types from multiple areas of ME/CFS research and from geographically disparate locations. The DMCC should develop and provide (as needed) a user friendly system for web-based recruitment and referral, tools for data mining, and a portal for access and integration of publicly available data resources. The DMCC should have computational sophistication for scaling the systems and tools to allow incorporation into a distributed, national clinical information network. The DMCC must consider privacy and confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing. The DMCC must also be able to work with consortia that have preexisting infrastructure (registries, patient databases, etc.), as well as those that are starting de novo. The Steering Committee will provide scientific and technical assistance and guidelines with respect to quality control, uniformity of data collection, management of the ME/CFS CRC database, and data analysis.

The DMCC will work collaboratively with the ME/CFS CRC to develop an overall website and individual websites for each of the ME/CFS CRCs. The actual design and implementation of the site(s) will be a collaborative activity of the DMCC and all of the ME/CFS CRCs through the Steering Committee (see below). The ME/CFS CRCs and the DMCC must work cooperatively to develop the web site resource and provide content related to ME/CFS. After receiving funding, the ME/CFS CRCs will work cooperatively with the DMCC to develop the web site resource and provide content related to ME/CFS. The DMCC will support the websites for communicating ME/CFS information. The ME/CFS CRCs and DMCC are encouraged to upload information about the biospecimens collected and how these will be shared within the ME/CFS CRCs and with outside investigators to help researchers utilize available biospecimens.

The DMCC will provide the overall project coordination, administration, data management, statistical support, and regulatory support that are necessary to successfully support the ME/CFS CRCs and fulfill the following goals:

1) Provide medical and scientific leadership to enhance the overall effectiveness of the ME/CFS CRCs.

2) Provide overall management of scientific activities around study and protocol development, data analysis and results dissemination.

3) Provide all administrative activities for the ME/CFS CRCs working closely with the Administrators at each of the ME/CFS CRCs.

4) Provide all logistical and other support services for the ME/CFS CRCs.

Specifically, the DMCC will be responsible for the following research support activities:

1) Provide a secure, customizable, scalable coordinated clinical data management system for the integration of clinical data with other unique data, including genetic, imaging, pathologic, and laboratory. This support should include developing and/or adapting new technologies and technological advances to facilitate data collection, storage, and management from clinical researchers working on many different areas of ME/CFS research and from geographically disparate locations;

2) Provide a portal and tools for integration of developed and publicly available datasets for data mining at the ME/CFS CRCs;

3) Provide for web-based recruitment and referral;

4) Provide a user-friendly resource site for the public, research scientists, and clinicians for the overall project, as well as for each of the ME/CFS CRCs;

5) Incorporate new approaches to distributed computing and federated databases;

6) Incorporate new approaches to database support and clinical study management to reduce the burden of rising costs of software as well as reducing the time and financial burdens of clinical site audits;

7) Address privacy and confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing;

8) Provide logistical and administrative assistance in arranging meetings of the Steering Committee and provide other operational support for the ME/CFS CRCs (e.g., communications, subcommittee meetings). The DMCC will prepare, distribute, and maintain minutes of the meetings;

9) Provide logistical and administrative assistance in arranging the annual ME/CFS CRC Director's meeting working together with the Steering Committee and NIH IC Project Scientists to plan this meeting;

10) While the consortia will be responsible for the training necessary at the onset of new clinical protocols, this training must be done in conjunction with DMCC personnel so that all new forms and documents can appropriately be incorporated into the ME/CFS CRC data management system;

11) Produce and maintain all ME/CFS CRC documents, including Operating Policy and Procedures manuals;

12) Develop and maintain a "listserv" interactive email system for communication within the Consortium;

13) Develop worksheets and study data forms, as needed, for the collection of data in multi-center studies, verify all data, develop tests, and maintain software for within-form edit checks at data entry. For worksheets, forms, or other tools developed within the ME/CFS CRCs, the DMCC will work to integrate the developed products into the data management system;

14) Develop uniform investigative clinical research protocols for data (and specimen) collection in collaboration with the Steering Committee;

15) Provide support services for the production of reports, graphics, and other materials as required;

16) Monitor ME/CFS CRC protocol adherence, data collection and data submission, and report violations to the Steering Committee as well as other required entities;

17) Work with the ME/CFS CRCs to establish, coordinate and produce applications for IRB submission and approval utilizing the new NIH Policy for Single IRB Approval (NOT-OD-17-027);

18) Coordinate site visits for auditing individual ME/CFS CRCs;

19) Provide scalable infrastructure. The ME/CFS CRCs and DMCC size and scope may expand in the future. A successful applicant must have the ability and resources to expand its operations to meet such future needs.

Organization and Governance

Data Management Coordinating Center (DMCC)

The DMCC is responsible for the overall coordination and administration of the ME/CFS CRC program; developing, maintaining and updating the Manual of Operating Procedures; protocol finalization and prioritization, accrual plans and advertising materials for each ME/CFS CRC collaborative study; regulatory support; tracking and compilation of data in secure data management systems, quality control, and data analyses; preparing minutes and reports for Network committees/ subcommittees, and the participating NIH ICs; statistical support, study design, and data analyses; preparing data reports; coordinating manuscript and presentation development; and coordinating meetings and activities of the ME/CFS CRC Steering Committee, the External Advisory Committee, and other ME/CFS committees and subcommittees.

ME/CFS CRCs

The ME/CFS CRCs are supported by a separate award, described in detail in RFA-NS-17-021. The ME/CFS CRCs are responsible for conducting clinical study protocols consistent with the mission of the ME/CFS CRC program. ME/CFS CRC investigators are responsible for identifying, recruiting and retaining study subjects; entering data promptly and accurately into a web-based data collection system provided by the DMCC; and contributing to manuscripts and otherwise disseminating research findings in a timely manner. Study protocols will be submitted as part of applications to RFA-NS-17-021. In conjunction with the DMCC and Steering Committee (SC), the ME/CFS CRC Steering Committee will be responsible for finalizing and prioritizing all protocols, developing common definitions and standardization across protocols, and analyzing and interpreting research results. The ME/CFS CRCs will also participate intellectually in all aspects of the Network governance, including developing Network procedures and subcommittees, finalizing clinical study protocols and costs for collaborative studies, developing a single IRB process for multi-site, collaborative studies, and writing template informed consents. The PD/PI is directly responsible for ensuring that all aspects of ME/CFS CRC Network protocols conducted at each site are being followed. The PD/PI will be expected to propose and conduct sub-studies and participate fully in Network committees. The PD/PI will be expected to develop regular communication with investigators and administrators at each of the ME/CFS CRCs to identify and address enrollment, screening, adherence to protocols, and other Network issues.

The ME/CFS CRCs will also be responsible for the planning and collection of high-quality biospecimens that will permit the longitudinal molecular analysis of disease pathogenesis and recovery, as well as disease stratification and mechanistic studies. These samples will be available to the wider scientific community for mechanistic work conducted under other funding mechanisms.

NIH Program staff are responsible for organizing and providing overall support for the ME/CFS CRCs and for the overall management of the grants for the Network. In addition to regular grant stewardship, Project Scientists will be involved substantially with the awardees as a partner, consistent with the Cooperative Agreement mechanism.

Steering Committee (SC)

The SC will provide overall scientific governance for the ME/CFS CRCs and DMCC and will be comprised of each ME/CFS CRC PD/PI and Administrator, the PD/PI of the DMCC, and NIH Project Scientists. A subcommittee from the SC nominates the Chair, but NIH Project Scientists reserve the right to approve the nomination and may otherwise appoint a Chair for the SC. The Chair rotates every year. The SC formulates and implements all policy decisions related to the work of the ME/CFS CRC Network and establishes its scientific agenda.

Protocols conducted during the project period may be one of those proposed by a funded ME/CFS CRC PD/PI in an application to a separate FOA or may be a modified or combined version of one of these protocols. The SC will appoint Protocol Teams, set timelines for protocol development and study implementation, and ratify changes to the overall ME/CFS CRC Network Manual of Procedures including updating to include procedures and guidelines for collaborative studies. The SC meets in-person at least one time annually and by teleconference monthly between the in-person meeting(s) to monitor the progress of the Network and consider special issues that arise. Administrative support for the SC will be provided by the DMCC.

Executive Committee (EC)

The EC and the DMCC provide the day-to-day scientific management of the Network. The EC, a subset of the SC, will be comprised of the SC Chair, the immediate past Chair, the rising Chair, PD/PI(s) of the DMCC, and Project Scientists from the appropriate NIH Institutes. The EC sets the agenda for the SC meetings and calls, and makes the necessary day to day decisions between SC meetings.

External Advisory Committee (EAC)

An independent External Advisory Committee, appointed by the NIH and funded through the DMCC, periodically reviews the activities of the ME/CFS CRCs and DMCC and provides input on the direction and progress of the program.

IRB Approval

The new National Institutes of Health (NIH) Policy on the Use of a Single Institutional Review Board of Record for Multi-Site Research (NOT-OD-17-027) has been announced. It is expected that applicants will utilize a single IRB for multi-site clinical studies where the same protocol will be utilized across the Centers. The intent of this policy is to enhance and streamline the process of IRB review and reduce inefficiencies so that research can proceed as expeditiously as possible without compromising ethical principles and protections for human research participants. IRB application and review will be coordinated through the DMCC for all multi-center clinical studies when possible. IRB approval for clinical studies being carried out in individual Centers will be the responsibility of each ME/CFS CRC.

NCATS will facilitate coordination with and access to the (Clinical and Translational Science Award) CTSA Program Consortium and is interested in collaborative projects to innovate the methods and tools needed in ME/CFS research. As appropriate, applicants are encouraged to employ the NCATS SMART IRB platform (https://ncats.nih.gov/expertise/clinical/smartirb) and Accelerated Research Agreements (https://www.ara4us.org/) for performance of clinical studies. NCATS will share SOPs, document templates, software tracking and management programs and other publicly available materials that have been developed in the CTSA Program.

Applicants are encouraged to consider potential collaborations on clinical studies with the CTSA Trial Innovation Network.

Administrative & Technical Committees

The ME/CFS CRCs and DMCC scientific and administrative work is assisted by a variety of committees whose membership is drawn from the ME/CFS CRCs, the DMCC, appropriate Project Scientists from NIH Institutes, and additional experts as needed. Committees may include protocol development committees, a publications committee, a finance committee, a biospecimen and a core lab committee. Other committees may be needed to support the research and outreach and partnership activities, and members will be drawn from the DMCC or from the ME/CFS CRCs and outside consultants, as needed.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Vicky Whittemore, PhD
Telephone: 301-496-1917
Fax: 301-402-1501
Email: whittemorevr@mail.nih.gov

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Facilities & Other Resources: The applicant must address the resources available in order to develop and make available a secure, customizable coordinated clinical data management system for collection, storage, and analysis of diverse data types and geographically disparate locations; to develop and provide (as needed) a user friendly system for web-based recruitment and referral, tools for data mining, and a portal for access and integration of publicly available data resources; to have computational sophistication for scaling the systems and tools to allow incorporation into a distributed, national clinical information network; and to address privacy and confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing. This should include a brief description of the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, geographic distribution of space and personnel, and consultative resources. Describe the resources available to provide logistical and administrative assistance, as well as operational support for website development and maintenance, meeting support, maintenance of consortium documents and email listservs, and coordination of site visits for audits (if needed).

All instructions in the SF424 (R&R) Application Guide must be followed. Describe the experience of the PD(s)/PI(s) managing subawards, if appropriate.

All instructions in the SF424 (R&R) Application Guide must be followed. The application budget should include:

-Costs for at least one in-person SC meeting annually.

-All travel costs for the members of the External Advisory Committee that will be appointed by NIH program staff after the ME/CFS CRCs and DMCC have been awarded.

-Support for publication, data sharing, and dissemination of results.

-Costs to support teleconferences/webcasts for the SC, protocol teams, and all technical and other committees supporting the ME/CFS CRC Network.

-Costs associated with coordinating the IRB approval for a collaborative project to be conducted by RFA-NS-17-021.

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

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

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

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

Research Strategy: Describe the proposed program for the DMCC. This description must include a detailed plan for addressing the DMCC responsibilities outlined below. The ability to carry out the proposed program must also be addressed. Describe the proposed data management and coordination program for the ME/CFS CRCs, indicating the experience in serving as a data management center for a large multi-institution research network. Describe the nature of the multidisciplinary team necessary to provide the internet, technical, and statistical resources required to maintain the DMCC, without duplicating information submitted on Biosketches. Applicants should describe the group expertise and experience of the PD(s)/PI(s) and other personnel as a whole and how they are suited to their roles in the DMCC without duplicating information submitted on Biosketches. Describe the leadership approach for governing the DMCC and coordinating and management of the ME/CFS CRCs, including plans for conflict resolution, and the organizational structure of the DMCC. Include plans and approaches for interacting with a consortium of basic and clinical investigators, institutions, and relevant organizations, including patient support organizations, focused on research on ME/CFS. To accomplish the program goals of the ME/CFS CRCs, the DMCC must serve as a core resource to the ME/CFS CRCs and be able to provide a number of services and activities. Describe novel organizational concepts and management strategies that will be utilized in the DMCC and in working with the ME/CFS CRCs. Include a description of methods that will be utilized for recruitment and outreach to individuals with ME/CFS.

Describe how the ME/CFS DMCC will be used by the ME/CFS Research Centers to store clinical data collected for ME/CFS CRC projects and cores. Describe how the ME/CFS DMCC will provide an essential data coordination tool for the entire ME/CFS research community through the development of a web-based data management system that provides tools to NIH-supported projects for both the collection and quality assurance of data in a standardized format. Describe how the ME/CFS DMCC will also coordinate the assembly of de-identified data into a common database thus enabling the query and distribution of aggregate data for the acceleration of ME/CFS research. For ME/CFS CRC projects, patient consent must allow broad sharing of de-identified data and biospecimen resources through the ME/CFS DMCC and the appropriate, approved biorepository, respectively, as appropriate.

Describe plans for the ME/CFS DMCC to conduct activities that are the sole purview of the DMCC including: 1) development of standardized electronic data forms, data formats and software for use across multiple cohorts and projects; 2) development of software to support study participant scheduling, site tracking, and facilitation and coordination of de- identified clinical and biospecimen data collection across multiple new cohorts and projects through an easy to use web-based entry system for submitters; 3) quality assurance checks of data entry and collections; 4) development of a user-friendly query system for users to evaluate availability of data and biospecimens within and across ME/CFS CRCs; 5) development of aggregate data report formats that are user-friendly and supported by well documented data dictionaries; 6) user training for both data submitters and data users; and 7) coordination of data and biospecimen summary reports and postings in collaboration with the approved biorepository. Describe plans for the development of all electronic data entry forms and quality assurance checks of de-identified data. Provide a proposed plan for work-flow and a proposed timeline for meeting the aims of the project, including strategies to ensure a robust and unbiased scientific approach to managing, integrating and coordinating the activities across the projects and resources required by the ME/CFS CRCs. Describe the ability for the DMCC to expand in future years to accommodate the possible growth and expansion of the ME/CFS CRCs.

Biospecimen Collection and Distribution

Investigators should include plans and justification for biospecimens collection using protocols developed by the ME/CFS DMCC together with the ME/CFS CRC Directors. A copy of the consent form for each study participant should be kept on file by the investigator but does not need to be sent with each sample.

Letters of Support: Each DMCC applicant must provide a statement that addresses how the institutional commitment will be established and sustained, and how the DMCC efforts will be given a high priority within the institution. The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the DMCC Director, assignment of space, sharing of resources, and/or other ways proposed by the applicant institution. Letters from a high-level institution official(s) (e.g., Dean of the School of Medicine, President, and Vice President for Research) should be attached confirming this commitment.

Consortium/Contractual Arrangements: Clearly describe the institutional commitment of the participating organization(s) (in the ways outlined above) to the DMCC Program.

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. Also include the following:

Consent forms should be submitted and must make it clear that any biological samples and de-identified clinical data will be appropriately shared with academics or industry.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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.

ME/CFS CRC clinical research projects and cores will be required to include the following General CDEs and specific ME/CFS CDEs when they become available:

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 )

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

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.

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

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

Does the proposed Center address the needs of the research program and resource that it will coordinate and manage? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research program and resource? Does this application provide a significant contribution to the support of the ME/CFS Collaborative Research Centers? If the aims of the application are achieved, how will the activities of the Centers be advanced? What will be the effect of these efforts on the methods, technologies, or services provided to the Centers?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing collaborative, multi-site research? Do the investigators demonstrate significant experience with coordinating collaborative basic or clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Does the application propose novel organizational concepts or management strategies in coordinating the research collaborations and resource the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed? Does the application develop or employ novel concepts, approaches, methodologies, tools, or technologies to facilitate data collection, storage, and management from clinical researchers working on many different aspects of ME/CFS in geographically disparate locations, including those that result in significant cost savings for clinical site audits and reduce the burden of rising costs of software? Are there novel methods for recruitment and outreach to health professionals, researchers, and community or patient organizations?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research ME/CFS Collaborative Research Centers and resource the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the projects and resources, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the program and resource are in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the program and resource? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects? Are the designs, methods, and analyses adequately developed, well integrated, well-reasoned, and appropriate to support the ME/CFS Collaborative Research Centers? Does the proposed approach provide for a secure, customizable, scalable coordinated clinical data management system for the integration of clinical data with other unique data, including genetic, imaging, pathologic, and laboratory? Does the proposed plan adequately address the informational tools necessary to support a cooperative research network such as: the development of a portal and tools for data mining; plans for web-based recruitment and referral; the development of a user-friendly resource site for the public, research scientists, and clinicians?

Will this approach include developing and/or adapting new technologies and technological advances for distributed computing and federated databases? Does the applicant adequately address privacy and confidentiality issues? Does the applicant acknowledge potential problem areas and consider alternative tactics? Is the structure of the program sufficiently multidisciplinary in order to meet the needs of the Network as well as the needs of the ME/CFS community?

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 children, justified in terms of the scientific goals and research strategy proposed?

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research program and projects it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Do the plans for integrating the activities of DMCC into the ME/CFS Research Network give confidence and sufficient evidence that such efforts are likely to be effective? Does the applicant have adequate resources at the institution to provide logistical and administrative assistance as well as operational support, including but not limited to website maintenance, meeting support, maintenance of Consortium documents and email listservs, and coordination of site visits for audits? Are resources available from the institution to allow expansion of DMCC activities to accommodate growth of the Network?

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.

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 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 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.

Not Applicable

Not Applicable

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.

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 (GDS).

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 CSR, 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 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 Advisory Neurological Disorders and Stroke 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.

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.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U24), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

The PD/PI of the DMCC will have the primary responsibility for defining the details of the project within the guidelines of the RFA-NS-17-021 and for performing the scientific activity, and agrees to accept close coordination, cooperation, and participation of the NIH staff in those aspects of the scientific and technical management of the project described below. Specifically, awardees have primary responsibility as described below.

ME/CFS Research Center Directors and the DMCC Director

The ME/CFS Research Center Directors with the assistance of the Data Management and Coordinating Center Director (DMCC Director) are responsible for the overall management of the Network. The relationship between the Centers and the Data Management and Coordinating Center (DMCC) should be one of equal partners.

Collaboration and Coordination

The collaboration of investigators in the Centers is highly encouraged based on shared interests and complementary talents and will be facilitated, when possible, by the DMCC.

Steering Committee Membership and Meeting Attendance

Each Center Principal Investigator, including the Principal Investigator of the Data Management and Coordinating Center, will be a voting member of the Network Steering Committee and participate in all Committee activities and decisions including, but not limited to, conference calls and special subcommittees as may be necessary. The Steering Committee shall be responsible for determining the frequency of meetings and scheduling the time and location. The Steering committee will establish the procedures for the function of the network, as outlined in section "Steering Committee."

Data Coordination and Management and Sharing

The ME/CFS CRC awardees will have primary rights to all data developed under those awards, subject to Government rights of access consistent with HHS and NIH policies. The DMCC will develop a data management system with the input of the Steering Committee. The Centers will place their data at the DMCC. The intention of the NIH is that the data collected within this ME/CFS CRCs will become a resource for the ME/CFS community and be made available to the broader scientific community consistent with achieving the goals of this program. Criteria and mechanisms for data sharing among investigators within the ME/CFS CRCs and with the scientific community will be developed by the Steering Committee.

The DMCC will also coordinate with NIH Project Scientists including registration with and data uploading to appropriate NIH-governed data repositories (for example, dbGaP). Data transfer to will be expected to occur on regular basis according to the data sharing policy for the ME/CFS Research CRCs that will be established by the Steering Committee and as approved by NIH.

Publication and Presentation of Study Findings

Timely publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of the ME/CFS CRCs and DMCC and NIH support. The Steering Committee will establish unifying procedures and criteria for presentation and publication of data developed within the ME/CFS CRCs so that these procedures and criteria are consistent across the ME/CFS CRCs.

Federally Mandated Regulatory Requirements

Each institution participating in the ME/CFS CRCs and DMCC is required to meet DHHS regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include:

1. methods for assuring that each institution at which ME/CFS CRCs and DMCC investigators are conducting clinical studies has registered with the Office of Human Research Protections (OHRP; http://www.hhs.gov/ohrp/) and has a Federal wide Assurance; that study protocols are reviewed and approved by the responsible Institutional Review Board (IRB) prior to patient entry; that active protocols are reviewed at least annually by the IRB, and that amendments are approved by the IRB.

2. methods for assuring or documenting that each patient, or patient's parent/legal guardian, gives fully informed consent to participation in a research protocol prior to the initiation of the clinical study.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

One representative from NINDS, will be designated to serve as the Program Coordinator for this cooperative agreement. The Program Coordinators for the DMCC and Project Scientists from the appropriate NIH ICs will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for awards, as described below.

Steering Committee Membership and Meeting Attendance

The NIH Program Coordinator from NINDS and the Project Scientists from the appropriate NIH ICs will serve on the Steering Committee (see below) and will participate in all Committee activities, including, but not limited to, meetings, conference calls, subcommittees, and special committees. They will assist in development of operating policies, quality control procedures, and policies that require cooperative action. While the Program Coordinator and Project Scientists will attend Steering Committee Meetings along with the Project Scientists from the ME.CFS CRCs, their cumulative votes may never exceed 1/3 of the total committee votes.

Monitoring Performance

The Program Coordinator and IC Project Scientists will assist the Steering Committee in the development of procedures for monitoring the performance of the clinical studies. This includes participation in periodic on-site monitoring with respect to compliance with protocol specifications, quality control and accuracy of data recording, and accrual.

Publication and Presentation of Clinical Studies Findings

The NIH staff may contribute, through review, comment, analysis, and/or co-authorship, to reporting results of the clinical studies to the investigator community and other interested scientific and lay organizations. Co-authorship by the NIH staff will be subject to approval in accordance with the NIH policies regarding staff authorship of publications resulting from extramural awards.

The Government, via the NINDS Program Coordinator, IC Project Scientists and Program Officials, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. Information obtained from the data may be used by NIH staff for the preparation of internal reports on the activities of the clinical studies. However, awardees will retain custody of and have primary rights to all data developed under these awards.

Program Stewardship

The assigned Program Official from NINDS will be responsible for normal programmatic stewardship and monitoring of this award. The Program Official will not serve as the substantively involved IC Project Scientist. They may receive input and recommendations from other NIH staff in monitoring the awards.

Areas of Joint Responsibility include:

All investigators within the Centers and the DMCC must be willing to work cooperatively and collaboratively both within the Network. The Network is expected to organize at least one annual meeting of the Network participants.

Steering Committee

A Steering Committee will be established to serve as the main governing body of the cooperative network. At a minimum, the Steering Committee will be composed of one representative from each of the Consortium, one representative from the DMCC, and the participating NIH IC Project Scientists. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 40 percent.

The Chairperson of the Steering Committee will be selected by the Steering Committee from among the non-Federal members during one of the early meetings of the Committee to be convened by the NIH Program Coordinator. All major decisions will be made by the Steering Committee. The Committee will meet at least semi-annually. As needed, the Steering Committee may establish subcommittees for special purposes. It is expected that most of the work of the Steering Committee will be performed in these subcommittees. The Centers and DMCC must abide by decisions of the Steering Committee.

The Steering Committee will have responsibility of facilitating the conduct of the clinical studies, promoting Network collaboration, establishing and updating the content of the web resource site, and establishing procedures for reporting results of Network studies. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

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

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: http://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

Email: support@grants.gov

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

Telephone: 301-710-0267

Vicky Whittemore, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917
Email: whittemorevr@mail.nih.gov

Nick Gaiano, PhD
Center for Scientific Review (CSR)
Telephone: 301-435-1033
Email: gaianonr@mail.nih.gov

Tijuanna Decoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-301-496-9231
Email: decostert@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.