Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
R01 Research Project Grant
None
This FOA invites investigation of biological and clinical measures of TBI-related progressive neurodegeneration and neurocognitive decline associated with increased risk for dementia and /or traumatic encephalopathy syndrome (TES) (clinicopathologic diagnostic counterpart to the neuropathological diagnosis of Chronic Traumatic Encephalopathy (CTE)). Investigations should be based on existing, well-characterized populations of patients with a history of TBI that are enriched for increased risk of cognitive impairment or dementia and can continue to be followed longitudinally; additional subjects may be recruited as appropriate. The overall goal is to advance knowledge of the underlying pathophysiology and clinical characterization of the chronic effects of TBI that distinguish static-chronic TBI cognitive impairment from those that lead to progressive neurodegeneration associated with TES and dementia. A critical feature of this FOA includes the broad sharing of clinical, neuroimaging, physiological, and biospecimen data and to create a data and associated biofluid resource for the broader community to further advance research in this area.
October 10t, 2021
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| November 10, 2021 | Not Applicable | Not Applicable | March 2022 | May 2022 | July 2022 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
Not Applicable
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 FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Background
In recent years, there has been a resurgence of both research and public interest in the long-term consequence of TBI, particularly as it relates to neurodegeneration, all-cause dementia and Chronic Traumatic Encephalopathy (CTE). Epidemiological data suggest that a history of traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s Disease (AD) and Alzheimer’s Disease Related Dementias (ADRD) and that the relative risk may be mediated by injury severity and frequency with increased severity and multiple insults resulting in higher risk. Frequency and severity of injury also contribute to the heterogenous expression of chronic static TBI-induced neurocognitive and neuropsychiatric sequelae. For example, more severe injuries often result in long-term static neurocognitive impairments that contribute to overall disability. However, the lack of selective and sensitive tools to differentiate the chronic static TBI-induced sequelae from progressive neurocognitive dysfunction can confuse the risk of dementia following TBI. Similarly, while TBI likely incurs risk for multiple progressive neurodegenerative paths, neither the diagnostic tools nor biomarkers exist to distinguish the potential risk for any specific neurodegenerative path. To date, the best characterized association may be the relationship between frequency of brain injury with postmortem CTE. Recently, initial diagnostic criteria have been published , for Traumatic Encephalopathy Syndrome (TES; CTE in living persons), however, these criteria require continued development and additional data for improving differential diagnoses. Advancing diagnostics of TBI-related neurodegeneration and associated cognitive impairment, including TES, through the discovery and validation of novel and existing tools has the potential to improve understanding of TBI's contribution to risk for specific dementias which could lead to improved clinical care and patient stratification in future clinical trials.
In 2012, the National Institute for Neurological Disorders and Stroke (NINDS) held the Report on the Neuropathology of Chronic Traumatic Encephalopathy Workshop that outlined research strategies and resources needed to fill knowledge gaps for advancing understanding of CTE including identifying CTE in living individuals and neuropathology. Discussion of identifying CTE in living individuals suggest that there may be multiple disease progression trajectories that may reflect distinct pathological processes related both to “dosing” of brain injury (a combination of both frequency and severity of exposure to head impacts and/or explosive blast) and patient-specific vulnerabilities. A primary recommendation from this workshop was the need to develop diagnostics for CTE in living persons. They concluded that the development of diagnostics should include neuroimaging, biofluid biomarker, clinical outcome assessments (COAs), and genetic susceptibility investigations into individuals with possible and probable CTE. In 2019, the NINDS held another workshop to determine the strategies, next steps, and approaches needed to overcome barriers for developing consensus criteria for the neuropathological diagnosis of CTE. While both the 2012 and 2019 workshops focused on CTE, the knowledge gap for understanding the association between a history of TBI exposure and risk for dementia is parallel and similarly understudied.
In 2011, the National Alzheimer's Project Act (NAPA) allocated resources "to prevent and effectively treat Alzheimer's by 2025." Since then, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held multiple research summits to assess the needs and opportunities relevant to this goal for Alzheimer's Disease (AD) and Alzheimer's Disease Related Dementias (ADRD). In particular, the NINDS has convened expert panels in 2013 and again in 2016 that were tasked with recommending research priorities for advancing the state-of-the-science for all ADRDs, including those due to multiple neuropathological mechanisms (i.e., Multiple Etiology Dementias--MED, and Vascular Contributions to Cognitive Impairment and Dementia (VCID), Including Vascular Cognitive Impairment and Vascular Dementia). Recommendations for MED emphasized the need to describe quantitatively the clinical synergies between different etiologies and identify molecular pathways that accelerate cognitive dysfunction or that protect cognition that are agnostic to specific pathologies, i.e., that might act on mechanisms of cell death or synaptic dysfunction common to more than one neurodegenerative process. Recommendations for VCID emphasized investigations of the contributions of additional risk factors for AD, including diabetes/metabolic syndrome, obesity, lipid metabolism, hypertension, diet, exercise, sleep head injury, and aging, on cerebrovascular function. At the 2019 NINDS-sponsored ADRD Summit, TBI was introduced as an Emerging Topic of interest with recommendations developed for understanding the mechanism(s) by which TBI incurs risk for AD, all-cause dementia, VCID, and MED. Included in the recommendations (Recommendation 8 – Priority 4) was to “Conduct clinical studies to characterize the clinical phenotype, phenotypic heterogeneity, clinical course, and effect modifiers ... of post-traumatic dementia in comparison to known dementia types.” Further, it was recommended to “develop TBI-AD/ADRD biomarkers ... to non-invasively identify the development of TB-AD/ADRD pathologies and track their progression over time in relation to dementia.”
Specific Research Objectives
Applications to this FOA will be expected to discover and develop biological and clinical measures of TBI-related progressive neurodegeneration and cognitive decline associated with increased risk for dementia including traumatic encephalopathy syndrome (TES) (clinicopathologic diagnostic counterpart to the neuropathological diagnosis of Chronic Traumatic Encephalopathy (CTE)). Results are expected to inform dementia risk prognoses for patients with history of TBI, using objective clinical and pathophysiologically relevant biological measures. Addressing this goal will require (1) enhanced, validated methods for assessing individual's lifetime exposure to TBI (across varying levels of frequency, severity, and time since injury), (2) accounting for chronic but non-progressive neurocognitive impairment following TBI, and (3) access to an existing longitudinal cohort with a history of TBI exposure and / or dementia cohort with measures of TBI-exposure history. Applicants to this FOA are expected to assess hypothesis-driven objective biological measures and clinical assessments of progressive neurodegeneration, neurocognitive impairment, and neuropsychiatric dysfunction that, in persons with a history of exposure to TBI, may catalyze pathological pathways associated with AD / ADRD and TES. Biological measures may include but are not limited to neuroimaging (such as CT, MRI and PET imaging), vascular reactivity, assessments of sleep, oculomotor and vestibular function, blood-based biomarkers, proteomics, transcriptomics, metabolomics, biofluid markers from samples of CSF and saliva, and known genetic markers of dementia risk.
To address the heterogeneity of post-TBI clinicopathology and extend the generalizability of results, applications to this FOA are expected to recruit participants with history of TBI across multiple injury severities and have plans to recruit individuals from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research, such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women. These individuals may include former athletes from a variety of sports but should not be limited to the recruitment of or enrich recruitment primarily with former American-rules Football players.
To ensure maximal value of this project, a critical feature of this FOA includes the broad sharing of clinical, neuroimaging, physiological, and biospecimen data through the Federal Interagency TBI Research (FITBIR) database and NINDS-supported biorepository BioSEND.
Areas of interest include, but are not limited to:
Research topics that are not responsive under this FOA include but are not limited to:
The study team should include expertise in TBI and expertise necessary to diagnose neurodegenerative disorders and recruit and follow a relevant study cohort. In addition, the multidisciplinary team should be able to collect and analyze high quality data such as MRI and PET, genetics, cognitive tests, CSF and blood-biomarkers. The study must include relevant TBI Common Data Elements and comply with the data sharing policies of the FITBIR Informatics System as outlined in NOT-NS-17-029.
NINDS recognizes that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. There are many benefits that flow from a diverse scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.
To support the best science, NINDS encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:
Common Data Element Use and Data Sharing
It is expected that applications will incorporate the NINDS Core TBI common data elements (CDEs), other appropriate CDEs in the NINDS TBI CDE set, and the Global Unique Identifier (GUID) server supported by NINDS and NIA. Studies are also expected to use NINDS CDEs for both outcome and non-outcome measures (including, but not limited to demographics, medical and injury history, history of abusive injury, family history, medications, neuroimaging, rehabilitation strategy, and standardized outcome assessments) as described by the NINDS CDE Project. Compiling the broad array of CDEs that may be necessary to accomplish the goals of this FOA may require searching across NINDS CDE Disease areas (e.g., TBI, Parkinson's Disease, Epilepsy, Headache, and Huntington's Disease). When appropriate biospecimen collection and processing should follow procedures outlined in the NINDS CDE program (see "Studies Involving Biospecimens" section below). To optimize widespread data sharing, whenever possible, clinical outcome and non-outcome measures should align with existing large federally-funded TBI-related dementia studies (e.g. DIAGNOSE & LETBI)
In order to advance the goal of widespread data sharing, investigators funded under this FOA are required to share all study protocols and data collected in this FOA via FITBIR. FITBIR staff will work with investigators to assist with data harmonization to the NINDS CDE program and the FITBIR Data Dictionary that is based on the NINDS CDE program. To reduce the burden of data element harmonization, it is recommended that applicants adopt existing TBI FITBIR Form Structures for demographics, medical history, family history, injury history, laboratory tests, and neuroimaging. For answers to frequently asked questions and how to contact FITBIR, please see: https://fitbir.nih.gov/content/contact-us. To ensure maximal value of the project for the broader research community, proposals funded under this FOA will be required to share a "limited" clinical dataset (e.g., clinical assessment & outcome measures, diagnoses, comorbid diagnoses, symptom lists, mechanism of injury, demographics, etc.), in a FITBIR limited-access "public” state no more than 1-year after collection. Further, studies collecting biofluid markers (e.g. blood-based, saliva, and CSF) are expected to collect samples that will be sent to and stored at the NINDS-supported BioSEND Biorepository (see below) as part of a growing biospecimen resource for broad distribution of these samples to qualified academic and industry researchers to advance basic, translational, and clinical research in TBI-related dementia
As the research strategy is prepared, it is important to note that NINDS believes applications will be greatly strengthened if the rigorous design, execution, and interpretation of the proposed studies and supporting data are adequately described. NINDS encourages investigators, whenever possible, to address these elements directly in their applications. Investigators are urged to discuss these issues with Scientific/Research staff prior to submission of applications (see:NOT-NS-11-023 and NOT-OD-15-103). 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.
Imaging Based Studies
Applications proposing to include neuroimaging approaches are expected, where appropriate, to align with the NINDS neuroimaging CDEs. To optimize widespread data sharing, whenever possible, imaging sequences should align with existing large federally-funded TBI cohort studies (e.g., TRACK-TBI, NCAA/DoD CARE Consortium, Long-Term Impact of Military-Relevant Brain Injury Consortium (LIMBIC)/Chronic Effects of Neurotrauma Consortium (CENC), Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE)).
Studies Involving Biospecimens
Applications proposing to collect biospecimens must use NINDS Human BioSpecimen and Data Repository BioSpecimen Exchange for Neurological Disorders (BioSEND) protocols and procedures, and all specimens collected and banked with BioSEND must come from individuals who have consented to banking and sharing broadly with academia and industry.
Note that costs for collection are NOT included as a component of the NINDS BioSEND Repository award. Therefore, most costs for the biospecimen banking are borne by the grantees utilizing this resource (see NOT-NS-15-046). Applicants planning projects in which biospecimens will be collected are strongly advised to consult the NINDS BioSEND Repository website for more information about samples banked at the repository (https://biosend.org). In addition, applicants are advised to consult with NINDS Biomarkers Repository staff to obtain a quote for biospecimen banking costs (email: [email protected]).
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
NINDS intends to commit $2.75M (direct costs) in FY 2022 to fund 3 to 5 awards.
Application budgets are not limited, but should rarely exceed $1,000,000 in direct costs per year, and need to reflect the actual needs of the proposed project.
Up to 5 years
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Letter of Intent
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:
The letter of intent should be sent to:
Nsini Umoh, Ph.D.
Telephone: 301-496-1447
Fax: 301-480-1080
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 FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Budget considerations should include, but are not limited to:
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: Provide the overall goals and/or hypothesis of the entire project and list separate Specific Aims to be accomplished, briefly outline the methods proposed, and summarize the expected outcomes.
Research Strategy: Describe the research strategy to accomplish the Specific Aims and how the research will advance knowledge of progressive TBI-related neurodegeneration and cognitive decline as compared to chronic-static post-TBI cognitive deficits, how a history of TBI may catalyze pathological pathways associated with TES and dementia, inform prognostic models for dementia risk (including TES) in persons with a history of TBI, assess the relative risk for developing TBI-related neurodegeneration in individuals with a history of varying levels of exposure to TBI, and / or contribute to the development of diagnostic methods for TES. Describe access to relevant existing longitudinal cohort with a history of TBI and relevance of this cohort for achieving the purpose of this FOA. Provide alternative approaches to addressing the research aims if the proposed approaches fail. Operational definitions should be provided for measures of TBI exposure including injury frequency and severity (e.g., "concussion", "repetitive head impacts", and "multiple TBIs"), and time since injury. The method and criteria for assessing prior history of TBI should be well described and reproducible. It is expected that the NINDS TBI "Core" common data elements (CDEs) will be collected.
Investigations should be conducted in existing, well-characterized populations of patients with a history of TBI, enriched for increased risk of cognitive impairment or dementia, that have been and can continue to be followed longitudinally. While applications should be based on an existing cohort, additional subjects may be recruited as appropriate. Applications to this FOA are expected to recruit participants with history of TBI across multiple injury severities and have plans to recruit individuals from diverse backgrounds including groups traditionally underrepresented in the biomedical, behavioral, and clinical research, such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women. These individuals may include former athletes from a variety of sports but should not be limited to, or enriched by, the recruitment of former American-rules Football players.
Applications should include diversity in scientific expertise, including expertise in TBI, dementia, and biostatistics and should detail a plan for supervising and coordinating the entire range of proposed activities. Additionally, applications should include plans for incorporating trainees and/or young investigators into the research team to facilitate the development of interdisciplinary scientific/clinical research expertise in the next generation of researchers. Applicants should include a timeline that includes recruitment goals and interim analyses.
A description of the approaches for dealing with missing data, and data outliers should be included in the statistical plan. Applicants are strongly encouraged to pre-register hypotheses, aim(s), design(s), and plans for statistical analyses to journals for peer review prior to beginning their project.
Applications must provide a description of the “limited-access dataset” composed of CDEs related to but not limited to demographics, diagnoses, outcome measures, comorbid diagnoses, symptom lists, mechanisms of injury, time since injury, etc... that will be submitted to the FITBIR informatics platform for limited-access “public” sharing no more than 1-year after collection. Applications collecting biofluids must describe the types and quantities of biosamples to be shared through the NINDS-sponsored BioSEND biorepository.
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.
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.
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.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit 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 Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the 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?
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?
Does the research team include appropriate diversity in scientific expertise, career stage, and individuals from diverse backgrounds including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women that will further the goals of this funding opportunity to understand TBI as a risk factor in dementia across the breadth of diversity in injury and patient characteristics?
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?
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?
Does the project propose to study an existing longitudinal cohort appropriate for achieving the purpose of this FOA?
Does the cohort include a well-characterized population of patients with a history of TBI and an increased risk of cognitive impairment and/or dementia?
Will the project assess multiple severities of TBI?
Are the TBI exposure related operational definitions quantifiable?
Are the method(s) and criteria for assessing patients' prior history of TBI that is clear and reproducible?
Are the timeline for recruitment and a plan for interim analyses feasible?
Does the application propose to assess differences in chronic-static neurocognitive changes versus progressive neurocognitive change following TBI?
Does the study propose hypotheses for how TBI may incur increased risk for dementia and / or TES?
Is the data management and curation plan, and description of data harmonization with the NINDS CDEs (e.g., clinical assessment & outcome measures, symptom lists, mechanism of injury, demographics, etc.) appropriate for submission to FITBIR?
Does the application describe a plan for including individuals from diverse backgrounds including groups traditionally underrepresented in the biomedical, behavioral, and clinical research, such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women?
If biofluids are proposed, does the study have appropriate informed consent for including samples in the BioSEND biorepository for broad sharing of the samples?
Are sufficient sample volumes being collected for the submission to the NINDS-sponsored TBI BioSEND biorepository resource?
Does the application describe the “limited-access” dataset to be shared through FITBIR?
Does the statistical plan include approaches for dealing with missing data, and data outliers?
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?
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.
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 Animal 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.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications 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.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/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 FOA.
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 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Nsini Umoh, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email: [email protected]
Lisa Opanashuk, Ph. D.
National Institute on Aging (NIA)
Phone: 301-827-5422
Email: [email protected]
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
LaToya Proctor
National Institute on Aging (NIA)
Phone: 301-827-7453
Email: [email protected]
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.