RFA-NS-27-011-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Aging (NIA)

Funding Opportunity Title

Single Source: Post-Stroke Vascular Contributions to Cognitive Impairment and Dementia (VCID) in the United States (U19 - Clinical Trial Not Allowed)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

Reissue of

RFA-NS-19-012

Related Notices

Funding Opportunity Number (FON)

RFA-NS-27-011

Companion Notice of Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.853, 93.866

Notice of Funding Opportunity Purpose

This is a non-competitive funding opportunity intended to fund a single award. The National Institute of Neurological Disorders and Stroke is announcing its intent to issue a single source cooperative agreement award to Massachusetts General Hospital to support the renewal of the Post-Stroke Vascular Cognitive Impairment & Dementia (VCID) program, an ongoing, multi-site clinical research initiative designed to elucidate mechanisms linking stroke to subsequent cognitive impairment and dementia. The award will enable completion of the scientific aims initiated under the original U19 cooperative agreement (RFA-NS-19-012) and advance national priorities described in the National Plan to Address Alzheimer's Disease.

This is a Notice of Funding Opportunity (NOFO) for a Single Source that will invite an application from Massachusetts General Hospital. Please see Section III, Eligibility for additional information. In accordance with standard NIH processes, the application will be peer-reviewed, and only a meritorious application will be considered for funding.

Funding Opportunity Goal(s)

To support extramural research funded by the National Institute of Neurological Disorders and Stroke (NINDS) including: basic research that explores the fundamental structure and function of the brain and the nervous system; research to understand the causes and origins of pathological conditions of the nervous system with the goal of preventing these disorders; research on the natural course of neurological disorders; improved methods of disease prevention; new methods of diagnosis and treatment; drug development; development of neural devices; clinical trials; and research training in basic, translational and clinical neuroscience.

Key Dates

Posted Date

June 30, 2026

Open Date (Earliest Submission Date)

August 24, 2026

Not Applicable

September 28, 2026

Not Applicable

July 2027

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date

September 30, 2026

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of 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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description his is a non-competitive funding opportunity intended to fund a single award. The National Institute of Neurological Disorders and Stroke is announcing its intent to issue a single source cooperative agreement award to Massachusetts General Hospital to support the renewal of the Post-Stroke Vascular Cognitive Impairment & Dementia (VCID) program, an ongoing, multi-site clinical research initiative designed to elucidate mechanisms linking stroke to subsequent cognitive impairment and dementia. The award will enable completion of the scientific aims initiated under the original U19 cooperative agreement (RFA-NS-19-012) and advance national priorities described in the National Plan to Address Alzheimer's Disease.

Vascular and Alzheimer's pathologies are the most frequent pathologies in the brains of individuals with dementia. Moreover, it is increasingly reported that mixed pathology dementias account for half or more of all dementia cases, with beta-amyloid and vascular disease constituting the most frequent combination of pathologies. Atherosclerosis, arteriosclerosis, microinfarcts, silent stroke, and diffuse white matter disease are also associated with increased risk of dementia. Therefore, the National Plan to Address Alzheimer's Disease (AD) recognizes the significance of vascular contributions to cognitive impairment and dementia (VCID) in Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD). To establish the National Plan research priorities for VCID and other ADRD disorders the National Institute of Neurological Disorders and Stroke (NINDS), with input from multiple stakeholders including the National Institute on Aging (NIA), holds triennial ADRD Summits that result in ADRD research milestones for the National Plan to Address Alzheimer's Disease. Among the highest priorities identified in the ADRD Summits have been the need to understand the relationships between cerebrovascular disease and AD/ADRD in order to target underlying mechanisms and reduce the burden of cognitive impairment and dementia. This is because - despite the established relationships among stroke, AD, and dementia - the specific types (e.g. ischemic versus hemorrhagic, vessel types and sizes, and anatomical locations) and magnitudes of stroke events that cause post-stroke VCID are almost entirely unknown, as are the specifics of comorbid clinical factors, including other AD/ADRD disorders that may synergize with stroke to cause cognitive decline. If successful, results from this study will support development of future clinical trials that test interventions designed to reduce the burden of VCID following stroke. From a clinical practice standpoint, knowledge gained through this program will increase understanding of personalized post-stroke medical management and planning needed by post-stroke patients.

This is a Notice of Funding Opportunity (NOFO) for a Single Source that will invite an application from Massachusetts General Hospital. Please see Section III, Eligibility for additional information. In accordance with standard NIH processes, the application will be peer-reviewed, and only a meritorious application will be considered for funding.

Scope of Research An application is requested for one large prospective clinical research study to determine associations between stroke subtypes, the clinical context in which they occur, and subsequent development of cognitive impairment, including dementia. The overarching goal of this research program is to determine the specific subsets of stroke events that cause (and do not cause) cognitive impairment and dementia in post-stroke populations in the United States and what additional clinical factors and comorbidities may causally synergize with stroke to result in or prevent cognitive impairment and dementia outcomes. The study must be sufficiently powered to answer these questions in typical US populations representative of people who experience stroke in the United States.

Specifically, the responsive application must incorporate:

Applicants are encouraged to leverage existing resources for VCID and stroke research, and other dementia centers and resources, as well as established prospective cohorts. Applicants are encouraged to follow or build upon standards for VCID clinical data and best practices for biospecimens established by MarkVCID. Applicants are strongly encouraged to consult with NINDS Scientific/Research Staff early on during the planning stage of their application (see Agency contacts, Section VIII). See also Applicant Webinar information under Section IV.7 below ("Other Submission Requirements and Information").

Non-Responsive Applications:

The following applications will be considered non-responsive and will not be reviewed:

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

Renewal

The OER Glossary and the How to Apply - Application Guide provides details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials. Note: Applications may propose activities involving human subjects that are not deemed clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

Contingent upon NIH appropriations and the submission of a meritorious application, NINDS intends to commit up to $10,000,000 total budget in FY 2027 to fund 1 award.

Award Budget

Application budgets need to reflect the actual needs of the proposed project and should not exceed $26,700,000 in direct costs over 4 years.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 4 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Only the following applicant is eligible to apply for this single source funding: Massachusetts General Hospital.

Please refer to Section 1. Notice of Funding Opportunity Information for more details.

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organization) 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 not allowed.

Required Registrations

Applicant organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

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. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator)

Only the PI/PDs associated with the award issued under RFA-NS-19-012 to Massachusetts General Hospital are eligible to apply for this single source funding. Please refer to Section I. Notice of Funding Opportunity Information for more details.

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 How to Apply - Application Guide.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions of Terms.

3. Additional Information on Eligibility Number of Applications

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

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

A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts) and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Required

Required

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Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

Overall Component When preparing the application, use Component Type 'Overall'.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall) Complete entire form.

PHS 398 Cover Page Supplement (Overall) Follow standard instructions.

Research & Related Other Project Information (Overall) Follow standard instructions.

Project/Performance Site Locations (Overall) Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall) Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

The PD(s)/PI(s) of the study must have experience and demonstrated excellence in the dementia and stroke research fields, in communication, in large-scale geographically dispersed clinical research projects, with 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 in, and provide a strong plan for facilitating interactions, e.g. data and sample collection, harmonization, transfer, sharing, etc., with other databases and NINDS Repositories.

The experience of each PD/PI must be carefully documented, and their roles and responsibilities must be well-defined. In addition, the 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 will be expected to also be the Administrative Core Lead and to commit at least 3 calendar 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.

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

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

PHS 398 Research Plan (Overall) Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims:

Describe the overall scientific objective of the proposed study; the individual aims; how the individual components contribute to these aims; and how the overall research objective aligns with the purpose of this RFA: to determine the specific subsets of stroke events that cause (and do not cause) cognitive impairment and dementia in post-stroke populations in the United States, and what additional clinical factors, as well as comorbidities including those along the AD/ADRD spectrum, may causally synergize with stroke to result in cognitive impairment and dementia outcomes.

Research Strategy:

The Research Strategy states the theme, vision and rationale for the proposed study, and provides an overview of activities planned during the project period to achieve the specific aims. Organize the Research Strategy Section into sections on Significance, Innovation, and Approach. Renewal Applications must also include a Progress Report.

Significance. The scientific rationale and need for a study to understand post-stroke VCID by determining subsets of stroke events that cause (and do not cause) cognitive impairment including dementia, and the role of comorbidities including other AD/ADRD, 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 on how the science of post-stroke 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.

Innovation. Describe how novel approaches, investigator expertise, and collaborative activities that are synergistic will advance the goals of this RFA, including unique contributions with strong potential to advance scientific knowledge, technical capacity, and, in the future, clinical practice, treatments and service, including preventative interventions.

Approach. The applicants should clearly define and justify selection of the target populations, including clearly defined questions, and rigorous approaches as outlined by the NIH that provide assurance of the durability of the results. The study should propose and justify selection of broad inclusion criteria and discuss strategies for robust enrollment, including identification of clinical sites that cover a representative population of the United States.

Include both a description and a table or graph of the overall project timeline and 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.

Progress Report for Renewal Applications: Summarize the specific aims of the previous project period and the importance of the findings, and emphasize the progress made toward achievement of the project goals. Provide robust evidence of accomplishments to date, including key milestones achieved, and describe challenges encountered, as well as how challenges have been addressed and mitigated. Explain any significant changes to the specific aims and any new directions. Discuss previous participant enrollment (e.g., recruitment, retention, inclusion of human subjects, etc.). Any change in PI(s) should be noted and a rationale for the change provided. Use the Progress Report section to discuss, but not duplicate information collected elsewhere in the application, and provide both: evidence supporting the feasibility of the proposed research, and a compelling justification for continued support.

Letters of Support:

A statement of commitment from each participating institution or organization to the PD/PI that demonstrates how the institution or organization will support the PD/PI's efforts to complete the trial must be provided. Additionally, provide a cover page in the application listing the names and institutions of all letters of support providers.

Progress Report Publication List:

Please provide a list of publications related to RFA-NS-19-012.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

Delayed Onset Study

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

PHS Assignment Request Form (Overall) All instructions in the How to Apply- Application Guide must be followed.

Administration Core When preparing your application, use Component Type 'Administrative Core.' All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administration Core) Complete only the following fields:

PHS 398 Cover Page Supplement (Administration Core) Follow standard instructions.

Research & Related Other Project Information (Administration Core) Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

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

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

Project /Performance Site Location(s) (Administration Core) List all performance sites that apply to the specific component.

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

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

Budget (Administration Core) Budget forms appropriate for the specific component will be included in the application package.

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

PHS 398 Research Plan (Administration Core) 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. 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 Project Management Plan described in 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 a description of the Project Steering Committee (PSC), comprising the Contact PD/PI, the PI of each of the Cores, and the NINDS Project Scientist. The PSC 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. In addition, include a discussion of the approach to managing Clinical Sites, criteria defining performance of the sites, as well as a plan describing how performance will be monitored and measured, and what actions may be taken if expectations are not met. Information on study progress to date, challenges encountered, and steps taken to address these challenges should also be included. In addition, any anticipated changes in the Administrative Core approach or leadership (if any) should be described and justified. The Administrative Core 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). Additional activities include 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. Also, describe how multidisciplinary team members will collaborate to accomplish the aims as proposed.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Do not include a Data Management and Sharing (DMS) Plan within this Component. If a DMS Plan is required for this NOFO, it must be included within the Overall Component.

PHS Human Subjects and Clinical Trials Information (Administration Core) When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

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

Statistics Core The Statistics Core will be responsible for developing a statistically rigorous and appropriately powered study design, conducting the statistical analyses to address the overarching goals of this program and providing biostatistical support throughout the study. When preparing your application in ASSIST, use Component Type 'Statistics Core.' All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Statistics Core) Complete only the following fields:

PHS 398 Cover Page Supplement (Statistics Core) Follow standard instructions.

Research & Related Other Project Information (Statistics Core) Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

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

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

Project /Performance Site Location(s) (Statistics Core) 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.

Research & Related Senior/Key Person Profile (Statistics Core) In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key personnel 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 (Statistics Core) 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.

PHS 398 Research Plan (Statistics Core) 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 stroke subtypes and cognitive impairment and dementia. Sample size calculations should be designed to permit evaluation of these associations in population subgroups of interest.

Include in this section a Statistical Analysis Plan (SAP) addressing the overall statistical approach. The SAP should define the analyses with adequate power to assess post-stroke incidence and progression of cognitive impairment/dementia in important subgroups, including stroke subtype and population characteristics.

If changes to the original statistical analysis plan are proposed, please delineate and justify the proposed changes.

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.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Do not include a Data Management and Sharing (DMS) Plan within this Component. If a DMS Plan is required for this NOFO, it must be included within the Overall Component.

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.

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

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

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

Do not enter a Study Record into the Statistics Core since the required study record details should be entered into the Overall component.

Delayed Onset Study Not applicable. Delayed onset studies are not permitted.

All instructions in the SF424 (R&R) Application Guide must be followed Recruitment and Retention Core 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, ensuring that study milestones are achieved.

When preparing your application in ASSIST, use Component Type 'Recruitment Core.' All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Recruitment and Retention Core) Complete only the following fields:

PHS 398 Cover Page Supplement (Recruitment and Retention Core) Follow standard instructions.

Research & Related Other Project Information (Recruitment and Retention Core) Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

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

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

Project/Performance Site Location(s) (Recruitment and Retention Core) 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.

Research & Related Senior/Key Person Profile (Recruitment and Retention Core) In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key personnel 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.

Budget (Recruitment and Retention Core) 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.

PHS 398 Research Plan (Recruitment and Retention Core) 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 progress to date and continuation of the implementation phase. This section should include the following:

Description of participant recruitment and retention to date.

Description of any challenges faced, methods to mitigate those challenges, and plan to achieve goals for enrollment and retention.

Evidence of continued availability of a sufficient number of prospective participants across the participating clinical sites.

Evidence of continued 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 an action plan 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: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Do not include a Data Management and Sharing (DMS) Plan within this Component. If a DMS Plan is required for this NOFO, it must be included within the Overall Component.

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.

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

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

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

Do not enter a Study Record into the Recruitment and Retention Core since the required study record details should be entered into the Overall component.

Delayed Onset Study Not applicable. Delayed onset studies are not permitted.

All instructions in the SF424 (R&R) Application Guide must be followed Repository Core The Repository is responsible for managing 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 'Repository Core.' All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Repository Core) Complete only the following fields:

PHS 398 Cover Page Supplement (Repository Core) Follow standard instructions.

Research & Related Other Project Information (Repository Core) Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?'…