Part 1. Overview Information

Key Dates

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.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer's disease (AD) and Alzheimer’s disease-related dementias (ADRDs) by 2025. ADRDs are defined as Frontotemporal Dementia (FTD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy Body Dementias (LBD), and Multiple Etiology Dementias (MED). Starting in 2012, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) held research summits to assess the needs and set AD/ADRD research implementation milestones. The NINDS ADRD Summit 2022 resulted in ADRD research priorities for advancing the state-of-the-science toward meeting Goal 1 of the National Plan. One of the recommendations from the 2022 ADRD summit for MED emphasized the need for improved and early antemortem diagnosis, as it relates to traumatic brain injury (TBI)-related ADRD Pathology and other focus areas.

Both TBI and exposure to repeated head impacts can result in a chronic TBI-related (cTBI) syndrome that manifests as a heterogeneous combination of symptoms across multiple domains, including but not limited to, the cognitive, behavioral, oculomotor, vestibular, disrupted sleep, psychosocial, and affective domains. Data from the Centers for Disease Control and Prevention (CDC) and National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) have shown that cTBI may negatively affect a person's quality of life and increase risk of seizures, accidental drug poisoning, infections, pneumonia, and decrease life expectancy. Further, there has been a resurgence of both research and public interest in the neuropathological consequence of cTBI, particularly as it relates to risk of Alzheimer's Disease and Alzheimer's Disease related dementia (AD/ADRD) and Chronic Traumatic Encephalopathy (CTE). In 2012, the National Institute for Neurological Disorders and Stroke (NINDS) convened the Neuropathology of Chronic Traumatic Encephalopathy Workshop that outlined research strategies and resources needed to fill knowledge gaps for advancing understanding of CTE including neuropathology. Following this workshop, the NIH launched a major effort to define the pathologic characteristics of CTE, supporting a set of CTE Neuropathological Diagnosis Consensus Conferences to develop consensus guidelines for the pathological diagnosis of CTE (https://academic.oup.com/jnen/article/80/3/210/6145887).

In 2019, NINDS hosted another conference to identify persistent gaps in knowledge related to neurodegeneration and neurocognitive decline associated with cTBI. (https://www.ninds.nih.gov/news-events/events/neuropathological-diagnosis-chronic-traumatic-encephalopathy-cte-next-steps-workshop). Several short and long term strategies were proposed, including (1) addressing reproducibility concerns through replication studies and specific technical criteria; (2) conducting CTE studies in additional cohorts, potentially including existing population-based cohorts representing a range of physiological and pathological phenotypes; (3) assessing roles and contributions of additional brain regions and components (e.g., white-matter abnormalities, neuroinflammation, glial cells, blood-brain barrier) in CTE neuropathology and clinical manifestations; and (4) employing a range of technologies to study tau isoforms and other suspected proteins involved in neurodegenerative/dementia-related proteinopathies. The investigators also enumerated multiple unaddressed issues including the role of comorbid neurogenerative disease including AD and ADRD, characterization of other proteinopathies involved in CTE (e.g., TDP-43, beta amyloid, vascular dysfunction, and alpha-synuclein positive lewy bodies), a need for neuropathological differential diagnoses, understanding of the effect of brain injury exposure on neurodegeneration, and clinical correlates to disease burden.

Specific Research Objectives and Requirements:

This NOFO intends to address knowledge gaps there were identified in the 2019 CTE conferences. Examples include but are not limited to:

1. Characterize the neuropathological features of cTBI associated with ADRD and neurocognitive decline and prevalence of cTBI-related ADRD diagnoses and CTE pathology
2. Elucidate how different neurodegenerative processes interact in cTBI
3. Identify associations between ADRD neuropathological burden (presence and severity of any single or multiple pathologies) and antemortem clinicopathologic symptoms.

A comprehensive characterization of the neuropathological features and neurodegenerative processes include but are not limited to identification of 1) microscopic changes, including proteinopathies (tau, beta-amyloid, alpha-synuclein, TDP-43), inflammation, gliosis, and neuronal loss, including structural biology approaches to characterize the structures of protein aggregates found in cTBI-related pathologies, as well as 2) macroscopic changes, including vascular pathology, hemorrhage, and cortical and white matter atrophy. When present, abnormal protein deposition should lead to identification of the specific pathological protein isoforms. Applicants are encouraged to utilize advanced methods and techniques to dissociate potential differences in protein structures. Further, to better understand the prevalence of mixed pathologies associated with cTBI-dementias, characterization of mixed pathologies is expected to be included.

To assess the relationship between postmortem cTBI neuropathological burden and antemortem clinicopathology, applicants should propose methods to assess the antemortem symptomatology and clinical presentation including degree of cognitive impairment, memory dysfunction, psychiatric symptoms and neuromotor deficits using the NINDS/FITBIR Clinical History Neuropathology Common Data Elements (CDEs). Each application is expected to include assessment of the relationships among TBI exposure (including repetitive head impacts, single and multiple traumatic brain injuries (TBIs) across TBI severity), length of survival after injury, co-morbidities (e.g., post-traumatic epilepsy), neuropathological burden, and risk for neuropathological dementia diagnoses. Applicants are expected have access to two or more existing brain banks with extensive collections of AD/ADRD diagnosed tissue. Each brain bank should specialize in collecting tissue related to a different AD/ADRD so that neuropathological comparisons can be made across a range of disorders. The aggregate tissue inventory across these brain banks should include an extensive collection of AD/ADRD diagnosed tissue, CTE diagnosed tissue, and tissue from person's with and without a history of TBI (as cTBI controls).

To achieve this goal, it is expected that a multi-site, multidisciplinary team with expertise in 1) neuropathological diagnosis of neurodegenerative disease, including CTE, 2) clinical assessment of dementia, including CTE and 3) the long-term clinical and pathophysiological consequence of TBI and head impact exposure will be needed. The NOFO intends to support studies that include at least one trainee and/or early-stage investigator (ESI) specifically a neuropathologist on the research team. It is expected that applicants include those with lived experiences (e.g., donor caregivers) into the case accrual process, design, and execution of the study. People with lived experience includes those: diagnosed, at risk, caregivers and loved ones, and those whose family member with the disease or condition is deceased.

To enable broad use of the study results, successful applicants will be expected to develop and maintain a publicly available digital library of pathology slides and associated diagnoses. This digital library is expected to include high resolution digital images of all slides. The study will also be expected to make collected tissue available for broad data sharing either through a brain bank resource with a catalog and sharing practices that meet the FAIR data standards or via the NIH Neurobiobank.

This NOFO intends to support applications that include the following aspects:

• NINDS/FITBIR TBI Neuropathological Common Data Elements (CDEs); both the retrospective clinical history and neuropathological CDEs with a minimum data collection of the Core recommendations. These CDEs and recommendations can be found on the FITBIR website (https://fitbir.nih.gov/chronic-tbi-related-neurodegeneration-cdes). Funded applications from this NOFO are expected to participate in future NINDS CTE Neuropathological Diagnoses Consensus meetings by providing at least one neuropathologist to participate.
• Cases from traditionally minoritized and marginalized populations, including racial and ethnic groups, individuals with a lower socioeconomic status (SES), individuals that have sustained a TBI due to intimate partner violence and/or cases from individuals that were once incarcerated or without housing.

Non-responsive studies include:

• Applications that are not focused on TBI as a risk factor for AD/ADRD
• Studies that do not propose to acquire new brain tissue specimens.
• Studies limited to only one TBI severity
• Applications that are limited to retrospective samples with no antemortem data addressing the Core Clinical History Neuropathology Common Data Elements (CDEs) including TBI exposure.
• Applications that include preclinical research studies using animal models.
• Studies that do not follow the NINDS/FITBIR CDE Neuropathology CORE recommendations
• Applications that do not include milestones
• Studies that do not include hypothesis-driven research or that are primarily descriptive.

Special Consideration:

Additional Plans:

• An administrative plan, which includes coordinating the integration and management of activities including management of reporting, establishing milestones, organizing communications among sites, and resolving disputes.
• A plan to house and process the post-mortem brain tissue sufficient to support the needs of the projects. Applicants will be responsible for histological processing of all post-mortem tissue needed for the projects. If previously collected pre-mortem brain tissue will be used, clear details on how the specimens were processed and stored must be provided. For any newly collected samples, applicants are encouraged to follow protocols established during the NINDS Neuropathological CTE Consensus Conference for biospecimen collection, blocking, staining, storage, and CDE use.Unlike the resource sharing plan that describes how the applicant will maintain a publicly available digital library of pathology slides, the brain banking plan should describe how the applicant will process the tissue.

NINDS urges investigators to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described at https://www.ninds.nih.gov/Funding/grant_policy. This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These recommended research practices include, where applicable, expressing clear rationale for the choice of affected cases, implementing appropriate controls describing tools and parameters clearly, blinding, randomizing, ensuring adequate sample size, pre-specifying inclusion/exclusion criteria, appropriately handling missing data and outliers, preplanning analyses, and using appropriate quantitative techniques. It is also strongly recommended to indicate clearly the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications.

Investigators should indicate whether data presented or cited in the application as key support for the proposed work were collected, analyzed, and reported in a rigorous and transparent manner as indicated above. A plan to address any ambiguity, weaknesses, or limitations in the prior research should be included in the application. Proposed experiments should similarly adhere to these high standards of rigor and transparency. The NINDS also expects that applications will conform to the principles outlined in Landis et al., 2012 and show consideration for biological variables described in NOT-OD-15-102. PCS-EMA applications deemed not responsive to the NOFO will be withdrawn without review.

Milestones: All projects should be supported by a timeline and yearly milestones for completion. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Achievement of milestones will be evaluated by NINDS, and funding of non-competing award years will depend on milestone accomplishment. Note that these awards will be managed as cooperative agreements; therefore, projects that do not comply with terms, conditions, and established milestones of the award and of this program may be terminated early.

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

Section II. Award Information

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Government

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

Other

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

Not Applicable

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

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

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

Applicant Organizations

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

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

Not Applicable

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Not applicable

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

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

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

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

The letter of intent should be sent to:

Nsini Umoh, PhD
Telephone: 301-480-7036
Email: [email protected]

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

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

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

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

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

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

Applications must include multidisciplinary teams with expertise in 1) neuropathological diagnosis of neurodegenerative disease, including CTE, 2) clinical assessment of dementia, including CTE and 3) the long-term clinical and pathophysiological consequence of TBI and head impact exposure will be needed. Studies must include at least one trainee and/or early-stage investigator (ESI) specifically a neuropathologist on the research team. It is expected that applicants include those with lived experiences (e.g., donor caregivers) into the case accrual process, design, and execution of the study. People with lived experience includes those: diagnosed, at risk, caregivers and loved ones, and those whose family member with the disease or condition is deceased.

R&R or Modular Budget

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

The budget will be developed as part of the pre-application process and must include all study-related costs not covered by Network infrastructure awards. The application must provide detailed annual budgets that will enable the project to meet study milestones. Separate itemized budgets must be prepared for each subcontract.

R&R Subaward Budget

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

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

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

Specific Aims: Specific Aims should outline the overall vision and goals for the application. These Aims must be hypothesis-driven, characterize neuropathological features and address mixed pathology of cTBI related dementia (including CTE), inform associations between neuropathological burden and antemortem clinicopathologic presentation of cTBI, elucidating how different neurodegenerative processes interact, and outline the prevalence of cTBI-associated neurodegenerative disease in the participating brain bank(s). Finally, the role and degree of TBI exposure in mixed pathology and neuropathological burden must be addressed.

Research Strategy:

Describe the research strategy for the project and how the research will advance knowledge regarding the following components of this NOFOs purpose:

1. Characterize the neuropathological features of cTBI associated with ADRD and neurocognitive decline and prevalence of cTBI-related ADRD diagnoses and CTE pathology
2. Elucidate how different neurodenerative processes interact in cTBI
3. Identify associations between ADRD neuropathological burden (presence and severity of any single or multiple pathologies) and antemortem clinicopathologic symptoms

Describe and justify the plan for case selection, matching, and criteria for neuropathological diagnoses. If the project is using post-mortem brain tissue that is provided by an external collaborator, criteria used to assign a neuropathological diagnosis should be described. Specimen collection and storage protocols should be clearly described. Application must incorporate the NINDS/FITBIR Neuropathology CDEs and must include the Core Neuropathology CDEs. Research projects must provide clear diagnostic criteria and/or operational definitions for 1) CTE based on the NINDS CDE Diagnostic Criteria, 2) cTBI-related AD/ADRD diagnoses (LBD, VCID, FTD, AD, MED), 3) TBI history and diagnoses including, but not limited to concussion, mild TBI, moderate TBI, severe TBI, and exposure to repetitive head impacts, 4) neurocognitive and neuropsychiatric assessments and must include the Core Clinical History CDEs from the NINDS/FITBIR TBI Neuropathology CDE collection (https://fitbir.nih.gov/chronic-tbi-related-neurodegeneration-cdes). Provide a concise review of the relevant literature and its rigor, detail available pilot data, and justify the proposed aims and methods (applicants must discuss scientific premise, scientific rigor, and biological variables). Provide alternative approaches to addressing the research aims if the proposed approaches fail.

Applicants must describe how each site and each investigator is uniquely positioned to contribute world-class expertise and cutting-edge resources towards addressing the aims. Outline the roles and responsibilities for each team member, including the individual(s) with lived experiences. Synergy must be evident among each site. Describe access to existing brain banks that specialize in collecting tissue related to different AD/ADRDs, CTE, and/or TBI that will enable neuropathological comparisons can be made across a range of disorders.

Applicants must consider the relationships among TBI exposure (including repetitive head impacts, single and multiple traumatic brain injuries (TBIs) across TBI severity), length of survival after injury, co-morbidities (e.g., post-traumatic epilepsy), neuropathological burden, and risk for neuropathological dementia diagnoses.

Applicants must include plans and methods for acquiring new brain tissue specimen (including controls) with particular emphasis on acquiring tissue from, females and traditionally minoritized and marginalized populations. This includes, but is not limited to, racial and ethnic groups, individuals with a lower socioeconomic status (SES), individuals that have sustained a TBI due to intimate partner violence, and/or cases from individuals that were once incarcerated or without housing.

Applicants must describe how tissue will be acquired and aggregated across multiple brain banks to include AD or ADRD diagnosed tissue, CTE diagnosed tissue, and tissue from persons with and without a history of TBI, including control cases.

Clear and quantifiable annual milestones creating go/no-go decision points for measuring the success of all the project's specific aims should be proposed.

Administrative Plan:

Each application should describe the study PI(s) research productivity, active research funding (NIH R01-equivalent or greater) at the time of submission, and capacity for visionary leadership of the study team. Each application should detail a plan for supervising and coordinating the entire range of proposed activities. Applicants must explain the roles and responsibilities of study team personnel including scientific leadership, and administrative management and coordination of the proposed activities. Applicants must include those with lived experiences (e.g., donor caregivers) into the case accrual process, design, and execution of the study. People with lived experience include those: diagnosed, at risk, caregivers and loved ones, and those whose family member with the disease or condition is deceased.

Applicants must include plans for holding regular meetings and facilitating communication between team members; prioritizing resource usage/strategies; monitoring progress and ensuring that milestones are completed in a timely fashion; and ensuring that data/tissue/specimens collected by the center are shared in a timely fashion must be clearly detailed. An annual in-person center meeting is strongly encouraged. Clear and quantifiable milestones (e.g., for cross-site meetings and communications, resource management, etc.) creating go/no-go decision points for measuring the success of all specific aims should be proposed.

Brain Banking Plan:

Each application must include a plan to house and process the post-mortem brain tissue. For any newly collected samples, the applicant must describe the protocols for biospecimen collection, blocking, staining and storage. Describe methods for detailing how previously collected tissue and biospecimens were processed and stored. Describe methods for harmonizing histological processing of newly and previously collected biospecimen. Describe all aspects of the resource that are innovative, and any technical or methodological innovations that will be developed during the duration of the project including all histopathological processing protocols. If the project is collecting or providing specimens, collection and storage protocols should be clearly described and standardized across collection sites. Unlike the resource sharing plan that describes how the applicant will maintain a publicly available digital library of pathology slides, the brain banking plan should describe how the applicant will process the tissue.

Letters of Support: Applicants must provide letters from the appropriate high-ranking institutional official(s) indicating the commitment of the institution to the study goals and specifying any institutional support or resources that will be made available to the PI(s). A letter of support and collaboration is required from any collaborating brain bank / tissue repository.

Resource Sharing Plan:

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

The following modifications also apply:

• To enable broad use of the study results, successful applicants will be expected to maintain a publicly available digital library of pathology slides and associated diagnoses. This digital library is expected to include high resolution digital images of all slides. The study will also be expected to make collected tissue available for broad data sharing either through a brain bank resource with a catalog and sharing practices that meet the FAIR data standards or via the NIH Neurobiobank.

• Consistent with achieving the goals of the program, plans for developing a publicly-available digital pathology library for distribution and sharing of assessed neuropathological tissue must be addressed.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

Data Management and Sharing Plan:

In order to advance the goal of widespread data sharing, investigators funded under this NOFO are required to share all data collected in this NOFO via FITBIR using the appropriate Traumatic Brain Injury | NINDS Common Data Elements (nih.gov)| NINDS Common Data Elements (nih.gov), consistent with achieving the goals of the NINDS CDE program. FITBIR staff will work with investigators to help them submit data types consistent with the FITBIR Data Dictionary and the NINDS CDE program; however, data quality assurance is the sole responsibility of the study team.

• Submission of data through the FITBIR informatics platform will fulfill the requirements of the DMS Policy, but a DMS Plan must still be included.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The Data Sharing Plan should conform with data sharing requirements for TBI research as outlined in NOT-NS-17-029 and updated in NOT-NS-23-046. Per NOT-NS-23-046, investigators involved in clinical (i.e., human subjects research) TBI studies that meet at least 1 of the following criteria (taken from NOT-NS-17-029) must submit their data to the FITBIR Data Repository.

1. TBI-related clinical trials (i.e., studies funded under any of the NINDS Clinical trial FOAs),
2. all unsolicited clinical (i.e., human subjects research) TBI research grants with a budget greater than or equal to $500,000/year in direct costs,
3. NINDS ancillary studies, regardless of budget, to either TBI-related clinical trials or clinical TBI research grants (i.e., human subjects research) with budgets greater than or equal to $500,000/year in direct costs, or
4. clinical (i.e., human subjects research) TBI research grants awarded under funding opportunity announcements (FOAs) with specific requirements for FITBIR data submission.

Clinical TBI studies that do not meet at least 1 of the aforementioned criteria must submit their data to the Meta Studies Module within FITBIR, as opposed to the Data Repository.

For answers to frequently asked questions and how to contact FITBIR, please see: https://fitbir.nih.gov/content/contact-us.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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) 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. See Section III of this NOFO for information on registration requirements.

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 the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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

Reviewers will 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 study that by its nature is not innovative may be essential to advance a field.

Overall Impact

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

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?

Specific to this NOFO:

• To what extent will the study aims, methods, and projects shed light on the prevalence of cTBI-related ADRD diagnoses and CTE pathology in the involved brain banks?
• How rigorous is the prior research that serves as the key support for the proposed project?
• How likely is the project to result in major (rather than incremental) scientific advances?
• To what extent will this study improve our understanding of the relationship between ADRD and cTBI-related neuropathological burden, antemortem symptoms and/or clinicopathologic presentation?
• How likely will the study aims, methods, and projects advance knowledge regarding the neuropathological features of cTBI, particularly as it relates to various levels of TBI injury frequency and severity?
• How well does the application describe opportunities for scientific advancement that would not be achieved by each site working alone (synergy)?
• Do the project's aims/hypotheses address an important aspect of the study’s overall strategy for advancing knowledge about either 1) neuropathological features of cTBI associated with ADRD and neurocognitive decline, and/or; 2) associations between neuropathological burden and antemortem clinicopathologic presentation of cTBI; and/or 3) inform the prevalence of cTBI-associated neurodegenerative disorders in the involved brain banks?

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?

Specific to this NOFO:

• How well does the application describe the roles and responsibilities of each team member?
• To what extent does the study team have expertise in data coordination, CTE, TBI, and neuropathology?
• How well has the applicant demonstrated a capacity for visionary leadership of an interdisciplinary team?

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?

Specific to this NOFO:

• To what extent does the project propose innovative use of human tissues or biospecimens in its approach to addressing its hypotheses?

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/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO:

• To what extent will the study enhance our current understanding of neuropathological variability associated with cTBI?
• How well justified are the case selections?
• How clear are the plans to address: inclusion (or exclusion) of cases on the basis of sex/gender, race, and ethnicity, and age?
• How clear is the plan to assess the prevalence of cTBI-related ADRD and CTE within the involved brain banks?
• Do the involved brain banks specialize in collecting tissue from different neurodegenerative diseases so that a broad range of cTBI-associated diagnoses are represented?
• Is there appropriate antemortem clinical data to correlate with neuropathological burden of cTBI?
• How detailed are the proposed milestones?
• Are milestones clear, quantitative, actionable, and establish feasibility for all aspects of the proposed research?
• Are the milestones covering all aspects of the proposed project?
• Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
• Are all equipment, methods, and/or services state-of-the-art, clearly described, appropriate for addressing the study’s hypotheses, and scientifically rigorous?

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

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 Plan

• How clear is the plan for establishing and maintaining effective communications and cooperation among investigators on a regular basis?
• How clear is the plan for developing and/or maintaining a digital library of pathology slides?
• Does the application provide a clear strategy for supervising and coordinating the entire range of proposed activities, including plans for monitoring progress and ensuring that component plans are implemented, accomplished, and all milestones are met?
• How clear are the plans for describing how the specimen/tissue will be processed?
• Does the study team have appropriate expertise and dedicate sufficient time to administrative activities?
• How appropriate is the leadership approach, governance and organizational structure for the project?
• Does the plan include clear and quantifiable milestones creating go/no-go decision points for measuring the success of its goals?

Brain Banking Plan

• How clear are the protocols for collecting and preserving tissue and/or biospecimen?
• To what extent does the application detail methods for harmonizing processing of newly and previously acquired biospecimen?
• Does the application include sufficient details of histological processing?
• Are all equipment, methods, and/or services state-of-the-art, clearly described, appropriate for addressing the study's goals, and scientifically rigorous?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Not applicable

Renewals

Not applicable

Revisions

Not applicable

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

As applicable for the study 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) (i.e., 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 NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications 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 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 Council.The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

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

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

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

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

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

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

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

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

Definitions:

NIH Program Official

A NIH Program Official (PO) will provide the standard programmatic oversight and stewardship of the projects, including review of pre-award and award documents/requirements, review of progress reports and budgets, approval of changes in scope, budget allocation or aims, review of milestones and any other programmatic issues that may arise. The PO will serve as an ex officio member of the External Advisory Committee.

NIH Project Coordinator

One or more NIH Program Staff will serve as Project Coordinator (PC), to monitor progress in scientific aims, identify possible collaborations with other NIH funded initiatives, and other scientific issues, and oversee collaborative projects amongst recipients. The PC will serve as a scientific representative of the NIH to the investigators in accordance with policies and procedures of the cooperative agreement mechanism. The PC will provide NIH scientific programmatic involvement with the recipient that is anticipated during the performance of the activities supported by this Cooperative Agreement. The PC will work closely with the PD/PI to maximize progress towards the goals of the project and the program and will serve as a voting member of the External Advisory Committee.

Roles and Responsibilities:

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

• Organize and host necessary annual scientific or programmatic meetings.
• Advertise the resources available to the community through outreach activities.
• Assemble the External Advisory Committee and participate in EAC activities.
• Manage and coordinate project activities scientifically and administratively at the recipient institution and with any collaborating institutions.
• Ensure that all data and information are disseminated according to the FAIR principles; that is data and information should be identifiable and annotated with metadata including data quality and assurances.
• Ensure that all data and information involving human subjects has the appropriate security and clearances.
• Wherever possible, adhere to the Open Science Initiative, to guarantee the right of others to read, redistribute, modify, and freely use any software.
• Update goals and milestones at the time of award and provide summaries of progress toward those goals, including the Project Management Plan, at least yearly, as requested by NIH. The milestones will be reviewed annually (and at other times, if necessary), and new milestones will be negotiated, as needed by working with the Program Official as appropriate.
• Participate in regular discussions with the NIH staff
• Ensuring that a publicly-available digital library of pathology slides
• Ensuring that all data are submitted to FITBIR.

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:

Program Official:

• Responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
• Review the progress of the project and monitor for compliance with NIH Grants Policy.
• Make recommendations to the NIH for continued funding based on performance and compliance with the Terms and Conditions of the award.
• Conduct more frequent progress reviews, with the possibility that the recipient submit quarterly progress reports should problems arise in the conduct of the study.
• Serve as an ex officio member of any External Advisory Committee.
• Ensure that activities proposed for development or implementation do not overlap or duplicate activities supported by other peer reviewed funding mechanisms;
• Assist with financial oversight of the study

Project Coordinator:

• Participate in the process of coordinating collaborative project efforts and setting priorities.
• In consultation with the program officer, provide advice in the development of operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• Serve as a non-voting member of any External Advisory Committee or Steering Committee as a representative of the NIH extramural staff.
• Serve as a liaison to the NIH, and as an information resource for the recipients about related research activities.

• Participate in regular meetings with the study staff as described in the milestones.
• Coordinate the efforts of the awardee with other awardees under this NOFO and those involved in related NINDS programs;
• Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• In consultation with the NIH Program Official, recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones 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 as appropriate).

Areas of Joint Responsibility include:

PD(s)/PI(s) will constitute the External Advisory Committee (EAC) and this committee is expected to consist of individuals who are not key personnel or collaborators of the key personnel of the award. The EAC meetings will include NIH staff and may include the PD(s)/PI(s) and other members of the funded project. The EAC will select one member to act as the Chair of the committee and the Chair may not be an NIH employee. The EAC will meet at least once a year.

Dispute Resolution:

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

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

Submission of data through the FITBIR informatics platform will fulfill the requirements of the DMS Policy, but a DMS Plan must still be included.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Management and Sharing (DMS) Plan. The DMS Plan should conform with data sharing requirements for TBI research as outlined in NOT-NS-17-029 and updated in NOT-NS-23-046. Per NOT-NS-23-046, investigators involved in clinical (i.e., human subjects research) TBI studies that meet at least 1 of the following criteria (taken from NOT-NS-17-029) must submit their data to the FITBIR Data Repository.

1. TBI-related clinical trials (i.e., studies funded under any of the NINDS Clinical trial FOAs),
2. all unsolicited clinical (i.e., human subjects research) TBI research grants with a budget greater than or equal to $500,000/year in direct costs,
3. NINDS ancillary studies, regardless of budget, to either TBI-related clinical trials or clinical TBI research grants (i.e., human subjects research) with budgets greater than or equal to $500,000/year in direct costs, or
4. clinical (i.e., human subjects research) TBI research grants awarded under funding opportunity announcements (FOAs) with specific requirements for FITBIR data submission.

Clinical TBI studies that do not meet at least 1 of the aforementioned criteria must submit their data to the Meta Studies Module within FITBIR, as opposed to the Data Repository.

4. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Lisa Opanashuk, Ph.D.
NATIONAL INSTITUTE ON AGING (NIA)
Division of Neuroscience (DN)
Phone: 301-827-5422
E-mail: [email protected]

Nsini Umoh, PhD

National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-480-7036
Email: [email protected]

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

Jeni SMITS
National Institute on Aging (NIA)
E-mail: [email protected]

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

Section VIII. Other Information

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

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