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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 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).

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.

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.

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:

Roderick A. Corriveau, Ph.D.
Telephone: 301-496-5680
E-mail: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	6 pages
Core (use for Statistics Core, Recruitment and Retention Core, Repository Core)	6 pages each

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required, maximum 1
• Administrative Core: required, maximum 1
• Statistics Core: required, maximum 1
• Recruitment and Retention Core: required, maximum 1
• Repository Core: required, maximum 1

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.

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

The PD(s)/PI(s) of the study must have experience and demonstrated excellence in the dementia and VCID research fields, in communication, in large-scale geographically dispersed clinical research projects, in neurological clinical data, in sharing data (collecting, banking, receiving, curating, distributing de-identified clinical data), and in informed consent in order to ensure successful leadership of this project. Ideally, leadership for the application will have proven success and a strong plan for facilitating interactions, e.g. data and sample collection, harmonization, transfer, sharing, etc., with other databases such as dbGaP, LONI, NACC, NINDS Repositories, MarkVCID and NCRAD.

The experience of each PD/PI must be carefully documented, and roles and responsibilities must be well defined. In addition, the responsibilities and authority of each PD/PI must be specified. The application must ensure that a multidisciplinary team of appropriate personnel are proposed at the participating sites to facilitate the implementation of all aspects of the project. Commensurate with the scale of this program, the Contact PD/PI must commit at least 3 person months per year to the project over its entire course.

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

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

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

Specific Aims: Describe the overall scientific objective of the proposed study; the individual aims of the proposed study; how the cores contribute to these aims; and the overall research objective that must align with the purpose of this RFA: to determine in a clinical setting the magnitude and anatomical features of incidental white matter lesions that are both necessary and sufficient to cause cognitive impairment and dementia. The study will include health disparity populations and will examine additional clinical factors and comorbidities, including along the AD/ADRD spectrum, that may be effect modifiers of the relationship between white matter lesions and cognitive impairment, including dementia.

Research Strategy: The scientific rationale and need for a study to understand the association between incidental white matter lesions and VCID should be well supported by preliminary data, clinical and/or preclinical studies, information in the literature and/or knowledge of biological mechanisms. Focus the project as a whole on how the science of VCID will be advanced by this research (including via increased understanding of mechanisms, targets, and risk, as well as advancing VCID biomarkers), and how the results of this study will affect clinical practice in the future. Describe the preliminary data on which the study is based.

The applicants should clearly define and justify selection of the target populations. The study should propose and justify selection of broad inclusion criteria and discuss strategies to enroll a geographically diverse population with a high proportion of women and minorities. Applications must address incidental white matter lesions and VCID in typical U.S. clinical populations and proposed studies must be sufficiently powered to address all major questions in at least two health disparity populations in addition to in men and women, for example racial and ethnic minority groups, socioeconomically disadvantaged populations, underserved rural populations, and sexual or gender minorities. Adequate scientific justification for the selection of the specific health disparity populations to be studied should be provided. If proposing to leverage existing resources for VCID research (e.g., prospective cohorts, research consortia, and/or dementia centers and resources), rationale, approach, and expected outcomes should be clearly described.

Include both a description and a table or graph of the overall project timeline and key milestones. The overall study timeline should include a description of key milestones that need to be met throughout the life of the study to ensure its success. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, measurable, results-focused and time-bound. Milestones may include, for example, timelines for IRB approval of the study consent; adoption of standardized clinical data (including imaging) and biospecimen collection, storage, and sharing; enrollment of first subject; enrollment of 500th subject; completion of enrollment; completion of first analysis (specify) for publication.

Letters of Support: A strong commitment to the proposed study by the leadership of the participating clinical sites should be demonstrated by including letters of support from the participating site signed by individuals with financial authority within the systems.

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. Separate Data Sharing Plans for the individual Cores and Projects are not expected.

For this FOA, the following criteria apply:

It is required that all biospecimens and clinical data collected (including imaging) and/or used for research under funding from this FOA have appropriate informed consent per NIH policy and as mandated by law. Applications must include plans for appropriately collecting, storing, and sharing de-identified clinical data.

When new biospecimens and/or clinical data (including imaging) are collected, consent must allow all enrolled individuals the opportunity to consent to share, including via NINDS repositories, their de-identified samples and data (including post-mortem tissue when possible) with researchers in academics, not-for-profits, and industry (for internal research only, for-profit use is not allowed). Considerations that investigators should include in consent forms for samples and data collected include the following:

• The sample and de-identified clinical data (including imaging) may be submitted to an NINDS (or other NIH) repository or database, research resources supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke
• The de-identified samples and clinical data will be securely stored at the repository or database
• No personal identifiers will be sent with samples and data
• Blood samples may be used for preparation of DNA, plasma, serum, and cells that may be used for cell culture, including stem cells, from which DNA can be prepared; other biological samples may be collected as applicable, for example cerebrospinal fluid or skin biopsies
• The de-identified samples (and their derivatives) and clinical data can be distributed to scientists for use in research and teaching only, and as such the Repository does not return results to donors
• The de-identified samples and clinical data could be used for research in any type of disease or genetic factors, not just vascular contributions to cognitive impairment and dementia
• The de-identified samples and clinical data will be available for research and teaching purposes to hospitals, universities, not for profit research organizations, and commercial organizations
• The de-identified samples and clinical data will be used for research only, and will never be distributed for profit
• There is a risk that someone could use information from the sample submitted, via DNA, to identify the person from which it came if it were matched with another DNA sample provided by that person. However, any user of this sample must agree not to use it for that purpose, and the risk, while real, is small.
• Individuals have the right to withdraw from this research project at any time. If possible, any samples contributed will be discarded if requested; however, because of the sample masking, NINDS may not always be able to identify which samples were donated by a specific person. Withdrawal from the study will in no way affect access to medical care for which the subject is eligible.

Embargo time for sharing with researchers that are not part of the funded application will be 2 years maximum for both de-identified clinical data (including images) and biospecimens from the date of collection; it is a requirement that all relevant agreements, including informed consent, recognize and comply with this requirement.

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 (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 with additional instructions as provided below:

For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

This section should refer to the Recruitment and Retention Core.

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

Address all ethical issues and issues related to human subject safety oversight for the study including developing informed consent documents or opt-out consents (if applicable).

3.2 Is this a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site?

Applicants should propose a consolidated or centralized IRB approach for study oversight to facilitate the appropriate and timely implementation of the study.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions. Answer "No" to "Are Human Subjects Involved" in this section.

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core 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.
• The Core Lead (Study Director) must be experienced in multi-center clinical research coordination and management, including success in meeting milestones and timelines. The Study Director's experience must be documented, and his or her role and responsibilities must be well defined.

The budget for the Administrative Core should reflect actual expenses related to study administration and management. The applicants should budget for expenses related to one in-person meeting of the Observational Study Monitoring Board (OSMB) during the Protocol Refinement and Study Start-up Phase, and one in-person meeting and one OSMB teleconference in years 2 through 6 of the study; in addition, expenses related to one in-person meeting each year of the External Advisory Committee (EAC) starting in year 2 should be included. NINDS will be responsible for appointing the members of the OSMB and EAC, as well as for direct support of the meeting and expenses for OSMB/EAC members; the Administrative Core budget should only reflect costs related to preparation of reports and other OSMB/EAC-related materials and expenses for key personnel to travel and attend in-person meetings. All in-person meetings of the OSMB and EAC will be held in the Washington, DC area. The budget should also include all expenses for a year-one Kickoff Meeting and an annual Investigator Meeting, to be held at sites proposed by the applicant; and meetings of the steering committee and subcommittees as needed (generally by teleconference or in conjunction with a planned in-person OSMB or annual Investigator meeting)

The budget for the Administrative Core should also include all costs related to implementation of the study at the participating clinical sites. Such activities may include but are not limited to screening, verifying participant eligibility, enrollment, performing baseline and follow-up measurements, ascertainment and adjudication of outcomes, data and biospecimen collection, and submission of data/specimens to the Repository.

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.

Specific Aims: Aims for this core should define key aspects of administration and management of the study.

Research Strategy: The Administrative Core is responsible for implementing the overall project management strategy in accordance with the Project Management Plan (to be included as an Appendix; see below). Project management should directly support the needs of scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet pre-defined study objectives. The research strategy must provide sufficient detail to demonstrate the ability to achieve the goals of the study within the budget and funding period and to manage and mitigate risks. Include discussion of the approach to managing Clinical Sites and criteria defining performance of the sites, as well as a plan describing how performance will be monitored and measured, and what corrective actions may be taken.

Given the diverse and complex challenges involved in the design and execution of this study, the award will provide for up to one-year initial protocol refinement and study start-up phase, to be followed by an implementation phase. The application should include a detailed description of the applicants' plans and proposed staffing for completing activities during the two phases, including a detailed timeline. Based on completion of the protocol refinement and study start-up phase, the awardee will recommend the final study protocol, consent documents and manual of procedures, which will be subject to review by the OSMB. The OSMB's recommendation to NIH to approve the study documents obtained during the initial one-year phase and NIH’s concurrence with the OSMB recommendations is a condition for transitioning to the implementation phase.

Letters of Support: If more than one site is proposed for study administration and management, letters of support from sites other than the Director's site are required.

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:

A Data Sharing Plan is not expected for this Core.

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.

For this FOA, include a Project Management Plan in the Appendix. The Project Management Plan should describe how team members will collaborate to accomplish the aims as proposed and should address the following components (maximum 4 pages):

• Project Steering Committee (PSC), comprising the Contact Principal Investigator, the Directors of each of the Cores, and the NINDS Project Scientist, will be responsible for overall leadership and scientific direction of the project, as well as for coordinating with other critical researchers and stakeholders in the field. The PSC will meet at least quarterly by teleconference.
• Activities of the Administrative Core, which will be responsible for logistically driving the project across the network of sites, including organizing and managing logistics for all meetings (including for the PSC and the scientific Cores), as well as an in-person kickoff meeting and annual meetings thereafter.
• Establishment, management, and coordination of subcommittees, including a Data and Samples Collection Subcommittee, a Repository Subcommittee, and a Sharing Subcommittee. Describe the responsibilities of the subcommittees and how they will interact with each other and the overall study leadership.
• A Team Management Plan. NIH strongly encourages applicants to form multidisciplinary teams that consist of clinical and non-clinical scientists with expertise in cognitive, statistical, population-based clinical research, and other relevant academic/industry experts and health disparities disease experts. This multi-disciplinary team should have the expertise needed to execute the research strategy. The Team Management Plan should describe how team members will collaborate to accomplish the aims as proposed.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

The Statistics Core will be responsible for developing a statistically rigorous and appropriately powered design and conducting the statistical analyses to address the overarching goals of this program and will provide biostatistical support throughout the study. 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.

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant's Project

Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions. Answer "No" to "Are Human Subjects Involved" in this section.

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

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

List the site or sites that will perform data management and provide biostatistical support.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core 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. The Statistics Core Director's role and responsibilities must be well defined and justified.
• 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.
• The Core Lead must be experienced in biostatistics and have experience in leading efforts of several PhD level biostatisticians.

Budget for the core should reflect actual expenses related to biostatistical design and support.

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.

Specific Aims: Aims for this core should define the key aspects of the study's statistical design, statistical analysis plan, and biostatistical support.

Research Strategy: This section should discuss in detail assumptions used in power calculations and provide evidence supporting these assumptions. The applicants are strongly encouraged to propose a study with high power to assess the associations between white matter lesion characteristics and cognitive impairment and dementia. Sample size calculations should be designed to permit evaluation of these associations by gender and in health disparity population subgroups.

Include in this section a Statistical Analysis Plan (SAP) addressing the overall statistical plan. The SAP should define the analyses with adequate power to assess incidence and progression of cognitive impairment/dementia in important subgroups, including white matter lesions and population characteristics (e.g., men/women, older/younger, differing baseline health status, differing race and ethnicity).

Letters of Support: if more than one site is proposed for biostatistical support, letters of support from sites other than the Statistics Core Director's site are required.

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:

A Data Sharing Plan is not expected for this Core.

Appendix:

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.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

The Recruitment and Retention Core will be responsible for developing strategies for identifying, recruiting, and retaining participants; overseeing implementation of the recruitment and retention protocol; and assuring that study milestones are achieved, as well as ensuring health disparities goals are met.

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.

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant's Project

Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions. Answer "No" to "Are Human Subjects Involved" in this section.

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

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

List the site or sites that will coordinate and lead recruitment and retention efforts. These coordinating site(s) may also participate in recruitment and retention of the participants but are not required to do so.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core 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.
• The Core Lead must have experience in successfully leading recruitment and retention of participants in large clinical trials or other clinical research studies. Members of the Key Personnel must have experience working with health disparity populations. Such experience must be documented, and Core Lead's role and responsibilities must be well defined.

Budget for the core should reflect actual expenses related to developing methods for and monitoring recruitment and retention of participants.

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.

Specific Aims: Aims for this core should define the key aspects of recruitment and retention of participants.

Research Strategy: Responsibilities of the Recruitment and Retention Core should be discussed, with reference to activities relevant to the initial protocol refinement and study start-up phase and the implementation phase. This section should include the following:

• Evidence of availability of a sufficient number of prospective participants across the participating clinical sites.
• Evidence of availability of a sufficient number of healthcare providers within participating clinical sites willing to have their patients participate in the study.
• An approach that addresses: 1) the expertise of the individual(s) responsible for screening, approaching and consenting potential participants; 2) the process for identification and screening of study participants; 3) primary and back-up recruitment strategies; 4) implementation of the consent process; 5) participant retention and adherence strategies; and 6) approach to tracking progress toward study milestones and developing corrective actions when necessary.

Letters of Support: if more than one site is proposed to oversee participant recruitment and retention, letters of support from sites other than the Core Director's site are required.

Resource Sharing Plan:

A Data Sharing Plan is not expected for this Core.

Appendix:

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.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

This core should manage the acquisition of clinical data, biospecimens, and the processing, storage, tracking, and analysis of brain images and biospecimens. 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.

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant's Project

Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions. Answer "No" to "Are Human Subjects Involved" in this section.

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

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

List the site or sites that will manage or perform specimen acquisition, processing, storage, tracking, and laboratory analyses.

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

In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core 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.

The Core Lead or Co-Leads (Repository Core Director) must be experienced in operating a biorepository and performing laboratory analyses. This experience must be documented, and Core Lead's role and responsibilities must be well defined.

Budget for the Repository Core should reflect actual expenses related to obtaining, processing, storing, managing, and analyzing clinical data, biospecimens and images. The cost of analysis for any proposed images or biospecimens should be separated from the other costs of collection, processing, managing, tracking or storage of the materials. The cost and budgeting for the core should start in the second year of the project except for modest planning cost in year one. The cost of transferring the samples at the study end to an appropriate NIH repository should be included.

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.

Specific Aims: Aims for this core should define the key aspects of the repository’s clinical, biospecimen, and image plan.

Research Strategy: This section should discuss how study data, biospecimens and images will be collected, processed, managed, tracked, and stored. The study will be required to prepare a public-use dataset and to share the biospecimens. The embargo period on all data and samples is a maximum of two years. There should be a discussion of scientific rationale of which biospecimens will be collected including those most relevant to the primary and secondary research objectives.

The plan should detail assumptions about obtaining biospecimens at baseline, and in any defined subsets of participants at periodic intervals during the study. The plan should discuss the most cost-efficient use of samples during the study as well as in response to outside requests.

The research strategy section should demonstrate the ability throughout the study to do the following:

• Manage and track clinical data, biospecimens and images
• Periodically withdraw samples from the repository
• Sub-aliquot the samples
• Ship samples, if necessary, to other laboratories supporting NIH-funded ancillary studies
• Conduct quality assurance analyses for high priority biomarkers
• Integrate the laboratory results with the study data

Plans should be provided for adherence to Good Laboratory Practices (GLP) and use of current best practices for bio-specimen management and quality control (e.g., the National Cancer Institute's Best Practices for Biospecimen Resources or the NHLBI Biorepository Guide).

Letters of Support: If more than one site is proposed for the Repository Core, letters of support from sites other than the Biorepository and Laboratory Director's site are required.

Resource Sharing Plan:

A Data Sharing Plan is not expected for this Core.

Appendix:

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.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

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, with the following additional instructions: Do not complete. For this FOA, follow the instructions for the PHS Human Subjects and Clinical Trials Information for the Overall component only.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the program 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 program 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 program that by its nature is not innovative may be essential to advance a field.

Does the program 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 program 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?

Are the scientific rationale and need for a program to address the proposed aims well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? Is this study necessary for establishing the association between white matter lesions and development and progression of cognitive impairment and dementia?

Is the proposed design appropriate to achieve the goals of the solicitation and the specific aims of the research? Does the program as designed have the potential to determine the specific characteristics of white matter lesions that cause (and do not cause) cognitive impairment and dementia, including in health disparity populations, and what additional clinical factors, as well as comorbidities including those along the AD/ADRD spectrum, may exacerbate or mitigate associations between white matter lesions and cognitive impairment and dementia outcomes?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the program? 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 programt 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 program?

Are the proposed staff's level of effort, expertise, roles and responsibilities sufficient to complete concurrently the multiple parallel activities that will be required in order to successfully carry out the research?

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

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 design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge as specified in the RFA, with the potential to impact future clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the program? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed program? 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 program 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?

Is the design justified and appropriate to address primary and secondary variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the study adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the study appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed measures, and duration of the study 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 to standardize, assure quality of, and monitor adherence to the protocol, data, imaging, and specimen collection guidelines appropriate? Does the application propose to use existing available resources, as applicable? If proposing to leverage existing data from other studies, how will those data advance the research?

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?

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

• Do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize and manage the proposed clinical sites as well as the investigators from the other cores? Do they have appropriate expertise in study coordination?
• Does the Project Management Plan adequately describe how team members will collaborate to accomplish the aims proposed in the Overall section?
• 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 and quality control been addressed?
• Have the applicants provided sufficient detail to demonstrate they can achieve goals of the core within the budget and timeline provided?
• Are the criteria proposed for monitoring performance of the clinical sites appropriate? Do participating sites cover a representative population of the United States? Do letters of support from participating sites demonstrate strong commitment to the proposed study?
• Are the activities of the protocol refinement and study start-up phase and implementation phase well defined and appropriate for the project? Do the plan and timeline for transitioning to the implementation phase have high likelihoods of success?
• Does the application adequately address the capability to conduct the study at the proposed sites? Are the plans to add or drop enrollment sites, as needed, appropriate?
• Is there evidence of the ability of the sites 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?

• Are the proposed staff's level of effort, expertise, roles and responsibilities adequate to run the statistics core?
• Are planned analyses and statistical approach appropriate for the proposed study design and methods?
• Does the Statistical Analysis Plan propose the pre-specified analyses with adequate power to assess associations in important subgroups (e.g., men/women, older/younger, differing baseline health status, differing race or ethnicity)?
• Are the power calculations appropriate and do they allow the opportunity to analyze measures of white matter lesion magnitude, location, and other characteristics along with health disparity variables?
• Does the Statistical Analysis Plan adequately describe how team members will collaborate to accomplish the aims proposed in the Overall section?
• Is there a plan to complete data analysis within the proposed period of the award?

• Do the individuals responsible for overseeing the approach to screening, approaching and consenting participants have the required expertise to complete these tasks?
• Is the recruitment and retention plan complete, feasible and realistic? Are the plans for recruitment outreach, enrollment, retention, 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?
• Are at least two health disparity populations in the U.S. addressed with sufficient power to answer the main scientific questions prioritized in this RFA? Are potential enrollment challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
• Is there evidence that there is a sufficient number of prospective participants across the clinical sites? Is there a sufficient number of healthcare providers at each of the clinical sites?
• Is the process for identification and screening of potential participants, as well as back-up strategies, clearly described? Is the process for implementing consent appropriate? Is the strategy for retaining participants adequately described?
• Are adequate plans for monitoring recruitment and retention, including meeting study timelines, proposed? Are the proposed interventions/corrective measures to address barriers to successful recruitment or retention study-wide or at individual clinical sites appropriate?
• Are the activities of the protocol refinement and study start-up phase and implementation phase well defined and appropriate for the project? Do the plan and timeline for transitioning to the implementation phase have high likelihoods of success?

• Does the proposed Core leadership have documented experience operating a biorepository, clinical database, and imaging repository? Are the roles and responsibilities of the Core staff well defined?
• Is there a clear description of how clinical data, biospecimens, and images will be collected, processed, managed, tracked, and stored?
• Is there a plan for preparing a public-use dataset and shipping samples to NIH or other public repository in the final year of the study?
• Is the rationale for selecting which biospecimens to collect appropriate?
• Do the applicants demonstrate the ability to manage and track clinical data, biospecimens and images? Will they be able to periodically withdraw samples from the repository and easily ship them to other laboratories? Are there quality assurance analyses for high priority biomarkers?

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

Study Timeline and Milestones

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 to increase the efficiency of participant enrollment and data collection, as appropriate?

Are the proposed milestones, which could include timelines for OSMB and IRB approval, initiation of the first active clinical site, subject enrollment, and biospecimen collection and storage, appropriate? Do the milestones allow assessments of feasibility and provide criteria for determining go/no-go decisions at each stage of the study?

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.

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.

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

Not applicable

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

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

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

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 Part 75, 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 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:

Upon implementation of the protocol, each field center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, study participant management, and data collection.

Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NINDS support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur with the concurrence by NINDS Program Officer to ensure objectivity of research.

Adherence to all applicable NIH/NINDS policies including for data sharing and human subjects as appropriate and consistent with achieving the goals of the program;

Performing all aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NINDS staff in those aspects of scientific and technical management of the study.

Submitting annual progress reports, other required reports, and meeting milestones during the funding period, in a format as agreed upon by NINDS program staff;

Accepting and implementing any other common guidelines and procedures developed for the initiative and approved by NINDS program staff;

Attending and actively participating in all calls and in-person project activities;

Serving as a chair or member of project committees if elected;

Attending in-person meetings organized by the Administrative Core with input from the NINDS, the Steering Committee, and the External Advisory Committee, and presenting up-to-date findings (including unpublished results) on ongoing projects;

Sharing study information and results in a timely manner with the research community broadly through conference presentations, publications, web announcements, reports to NINDS program staff, and other mechanisms; manuscripts should be submitted to the NINDS Program Officer within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained;

Acknowledging NINDS/NIA support by citing the NINDS grant number as identified on the award notice in all publications, posters, oral presentations at scientific meetings, seminars, and any other forum in which results of this co-funded research are presented.

Establishment of informed consent such that when new clinical data and biospecimens are collected, consent allows all enrolled individuals the opportunity to share via NINDS Repositories their de-identified data and samples with researchers in academia, not for profit organizations, and industry (for internal research use only, for profit use is not allowed). Assurance that the de-identified clinical data and samples will be securely stored and can be distributed to scientists for use in research and teaching only. Assurance that the de-identified data and samples will be available for use in any type of biomedical research, not only for research on VCID.

Obtaining prior written approval of the NINDS Grants Management Specialist in consultation with the NINDS Program Officer for a change in any of the key personnel identified in the Notice of Award.

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 DHHS, PHS, and NIH policies.

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

NINDS program staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination.

An NINDS Program Officer will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. The NINDS Program Officer retains the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award including biospecimen and data sharing requirements as appropriate and consistent with achieving the goals of the program.

An NINDS Project Scientist will be responsible for contributing to the refinement or revision of research protocols or approaches as warranted; serving as a liaison between the awardees, the NINDS Advisory Neurological Disorders Council and the larger scientific community; serving on committees of the project as appropriate; assisting in promoting the availability of data and resources developed in the course of this project to the scientific community at large; assisting awardees in the development of policies for dealing with situations that require coordinated action, if needed.

NINDS program staff will appoint members of and manage the Observational Study Monitoring Board (OSMB) to monitor study progress and an External Advisory Board (EAC) to assist in overseeing the broad direction of the project. These boards will be managed by and will report to the NINDS; formal input may be solicited only by the NINDS. The OSMB will meet approximately twice annually and the EAC will meet once per year.

Areas of Joint Responsibilities include:

A Steering Committee, composed of the Principal Investigator, as well as the principal investigators of the specialized core facilities, and NINDS and NIA Scientific Officers (Project Scientists). The NIH Project Scientist will have voting membership on the SC and, as appropriate, on its subcommittees. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. Awardees will be required to accept and implement the common protocol and procedures approved by the SC. As the components of the SC may be geographically dispersed, the SC should meet with at least monthly conference calls, supplemented as deemed necessary by face to face meetings. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement all policies governing the study conduct 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 will be convened and will vote to resolve the dispute. The Dispute Resolution Panel will have three members (with one vote each): a designee of the award governing body chosen without NIH staff input, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two Panel members. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 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.

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, 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: 301-945-7573

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

Roderick A. Corriveau, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: [email protected]

Claudia Moy, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]

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