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
  • Check for any recent Notices of NIH Policy Changes that may impact application requirements.
  • January 23, 2026 - NIH Pause on New Submissions to the NIH Human Embryonic Stem Cell Registry and Request for Information on Reducing Reliance on Human Embryonic Stem Cells in NIH-Supported Research. See Notice NOT-OD-26-031.
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
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
Not Applicable September 28, 2026 Not Applicable March 2027 May 2027 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

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:

  • A collaborative network of sites with the expertise, capacity, and access to target populations needed to achieve the overarching purpose of this RFA. The network should include clinical and non-clinical scientists with expertise in stroke, VCID, imaging and other relevant biomarkers, clinical data collection and management, cognitive impairment including dementia, statistical approaches, population-based clinical research, relevant anatomy, relevant comorbidities, and vascular biology.
  • Stratification and hypotheses regarding not only cardio- and cerebrovascular risk and disease, but also regarding common sporadic clinical comorbidities, as well as AD/ADRD comorbidities.
  • Inclusion criteria and stratification based on severity of the index stroke event, stroke type, and stroke location.
  • Tracking cognitive trajectories including whether the following occur: cognitive decline at the time of and following the index stroke; recovery or non-recovery following cognitive decline; resistance to cognitive decline at the time of and/or following the index stroke.
  • Identification of factors associated with cognitive recovery versus non-recovery and/or progressive cognitive decline following the index stroke.
  • A study design that considers acceptable timing of enrollment in relation to the index stroke as well as the proposed optimum follow-up period to establish incidence and progression of cognitive impairment including dementia.
  • Use of relevant biomarkers including VCID diagnostic and progression biomarkers that have been or currently are being validated in systematic multi-site studies; further development and validation of these VCID biomarkers in this high throughput clinical research study; inclusion of amyloid-beta and tau biomarkers of Alzheimer's pathology during life.
  • Collection, managing and analysis of clinical data (including imaging) and biospecimens needed to meet the overarching goals of this RFA using methods that are standardized, rigorous and follow or improve upon best practices for VCID.
  • Approaches to address mechanisms when possible, including by determining interrelationships (cross-sectional and longitudinal) among the stroke event, overall cerebrovascular and cardiovascular disease and risk factors (including sex and other demographic differences), dementia-relevant genetic variants (including ApoE) and mutations including those known to cause VCID (e.g. in Notch 3) and cause or be a risk for clinical Alzheimer's disease (e.g. APP, PS1, PS2, PICALM, CLU, TREM2).

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: 

  • Applications for projects not previously funded under RFA-NS-19-012 
  • Applications not focused on AD/ADRD

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. 

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

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

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

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.

Component Component Type for Submission Page Limit Required/Optional Minimum Maximum
Overall Overall 12 Required 1 1
Administrative Core Administrative Core 6 Required 1 1
Statistics Core Statistics Core 6 Required 1 1
Recruitment Core Recruitment Core 6 Required 1 1
Repository Core Repository Core 6 Required 1 1

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:

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

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)

  • In the PD/PI section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key 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 (Study Director) should be the Contact PD/PI for the entire application and 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. 

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:

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

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:

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

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:

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

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?' 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) (Repository Core)

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.

Research & Related Senior/Key Person Profile (Repository 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 or Co-Leads (Repository 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 (Repository Core)

Budget for the Repository 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 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.

PHS 398 Research Plan (Repository Core)

Specific Aims: Aims for the Repository 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, stored, and distributed. The study will be required to prepare a public-use dataset and to share the bio-samples. There should be a discussion of scientific rationale of which biospecimens will be collected including why they are relevant to the primary and secondary research objectives.

The research strategy should detail plans for obtaining biospecimens and de-identified clinical data at baseline, and at periodic intervals during the study. The plans should discuss the most cost-efficient collection and use of samples during the study, as well as distribution within the project and in response to outside requests. The research strategy section should demonstrate the ability throughout the study to do the following:

Manage and track de-identified clinical data, biospecimens and images.

Distribute clinical data, biospecimens and images, both to study sites and to other laboratories supported by separate NIH funds.

Conduct quality assurance for data, biospecimens and images.

Integrate the laboratory results with the study clinical data.

Best practices for VCID clinical data, images, and biobanking established by the MarkVCID consortium should be followed, or modified with justification, for the purposes of this study.

Plans should be provided for adherence to Good Laboratory Practices (GLP). Other references for best practices for bio-specimen management and quality control include the National Cancer Institute's Best Practices for Biospecimen Resources, the NHLBI Biorepository Guide, and the National Institute on Aging Biospecimen Best Practice Guidelines for Alzheimer's Disease Centers.

Provide a report describing clinical data, biospecimens and imaging acquired to date. 

Letters of Support: If more than one site is proposed for the Repository, letters of support from sites other than the Biorepository and Laboratory 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 (Repository 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 Repository core since the required study record details should be entered into the Overall component. 

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply- Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer 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 form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in How to Apply - 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. 

Mandatory Disclosure

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact - Overall

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

Scored Review Criteria - Overall

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

Significance

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

Investigator(s)

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

Innovation

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

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex, 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?

Specific to this NOFO:

  • To what extent does the application describe the progress made toward achieving the goals of the initial award, and is it satisfactory? 
  • To what extent does the application provide robust evidence of accomplishments to date, including key milestones achieved, challenges encountered, and how those challenges were addressed?  
  • To what extent does the application describe how progress during the prior funding period supports the feasibility of the proposed research, and provide a compelling justification for continued support?

Environment

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

Additional Review Criteria - Overall

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.

Administrative Core:

  • Are the procedures and methods for standardization of data, for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? 
  • In what ways are the criteria proposed for monitoring performance of the clinical sites appropriate? 
  • Are plans to add or drop enrollment sites, as needed, appropriately described?
  • To what extent is there evidence of the ability of the sites to operate within the proposed organizational structure?

Statistics Core:

  • In what ways are the planned analyses and statistical approach appropriate for the proposed study design and methods?
  • To what extent does the Statistical Analysis Plan adequately describe how team members will collaborate to accomplish the aims proposed in the Overall section?
  • What is the plan to complete data analysis within the proposed period of support, and is it adequate?

Recruitment and Retention Core:

  • 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 realistic, and is the plan to monitor accrual adequate?
  • Are the potential enrollment challenges and corresponding solutions discussed, and are satisfactory back-up strategies clearly described to assist with recruitment and retention?

Repository:

  • How well have the applicants demonstrated the ability to collect, manage and track clinical data, biospecimens and images?
  • What are the appropriate quality assurance analyses proposed for high priority biomarkers?
  • Is the plan for preparing a public-use dataset and shipping samples to a public repository in the final year of study satisfactory?

Protections for Human Subjects

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

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

This NOFO only accepts applications that do not propose clinical trials. Note: Applications may propose activities involving human subjects that are not deemed clinical trials.

Inclusion of Human Subjects Policies

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for inclusion. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the American Veterinary Medicine Association (AVMA) Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

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

Renewals

For Renewals (as applicable), the committee will consider the progress made in the last funding period.

Revisions

For Revisions (as applicable), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations - Overall

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

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

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

Applications will be assigned to NINDS. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDS) 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants."  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

  • ongoing and consistent access to HHS owned or operated information or operational technology systems; and
  • receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

  • Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
    • Identify:
      • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
    • Protect:
      • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
      • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
      • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
      • Regularly backup sensitive data and test backups.
    • Detect:
      • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
    • Respond:
      • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
      • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
    • Recover:
      • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

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 (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

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

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

  • Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
  • 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 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 recipient 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.
  • Attend and actively participate in all calls and in-person project activities.
  • Being willing to serve as a chair or member of project committees if elected.
  • Attending in-person or virtual 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, if applicable) are collected, consent allows all enrolled individuals the opportunity to share via NINDS Repositories their de-identified data (and samples, if applicable) to researchers in academic, not for profit, and industry. Assurance that the de-identified clinical data and samples, if applicable, 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, if applicable, will be available for use in any type of biomedical research, not only for research on post-stroke 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.
  • Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. 

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.
  • The NINDS Project Scientist is responsible for contributing to the adjustment of research protocols or approaches as warranted; serving as a liaison between the recipients, the NINDS Advisory 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 recipients in the development, if needed, of policies for dealing with situations that require coordinated action. 

Areas of Joint Responsibility include:

  • A Steering Committee, composed of the principal investigator, as well as the principal investigators of the specialized core facilities, and NINDS Scientific Officers (Project Scientists). The NIH Project Scientist will have one vote on behalf of NIH 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. Recipients 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. Recipient members of the Steering Committee will be required to accept and implement all policies governing the study conduct approved by the Steering Committee.
  • The NINDS will establish an independent OSMB to assist in overseeing the broad direction of the project.  The OSMB will contain members who are not NIH employees and are not in the consortium. The OSMB will be convened by NINDS and will provide independent monitoring of participant safety, data quality and study progress, and provide feedback and recommendations to NINDS. 

Dispute Resolution:

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

3. Data Management and Sharing

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.

4. Reporting

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

Application Submission Contacts

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.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

Scientific/Research Contact(s)

NINDS DCR ADRD Program Staff 
Email: NINDS_DCR_ADRD_mail@mail.nih.gov

National Institute on Aging (NIA)
NIA-NOFO-Scientific@nih.gov

Peer Review Contact(s)

Center for Scientific Review (CSR)
Email: NOFOReviewContact@csr.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer 
National Institute of Neurological Disorders and Stroke (NINDS) 
Email: ChiefGrantsManagementOfficer@ninds.nih.gov
 

National Institute on Aging (NIA)
NIA-NOFO-Grants@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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