It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Data from the Centers for Disease Control and Prevention illustrate the high burden of pediatric brain injury with approximately 640,000 traumatic brain injury (TBI)-related emergency department (ED) visits, 18,000 TBI-related hospitalizations, and 1,500 TBI-related deaths reported among children 14 years of age and younger in 2013. Since early adolescence is a critical period for several neurodevelopmental processes associated with cognition, emotion, and psychosocial behaviors, the pre-adolescent and adolescent age groups may be at increased risk for the effects of brain insult and injury that can cause negative long-term neurobiological and behavioral consequences. Therefore, this FOA will focus on Early (11-14 years old) and Middle (15-17 years old) adolescent stages as defined using the Bright Futures guidelines developed by the American Academy of Pediatrics.

Both concussion itself and exposure to repeated head impacts can lead to a complex expression of concussive-type symptoms. A concussion can present 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. Usually, these symptoms are self-reported and resolve within 7 to 10 days after onset; however, a subset of patients experience prolonged, persistent concussive symptoms beyond the typical recovery period. Further development of a clinically relevant risk-stratification algorithm for identification of the subset of patients that will experience persistent concussive symptoms would have utility both in clinical management and patient enrichment for future clinical trials. Currently, clinical outcome assessment measures including balance, fatigue, migraine history, and mental health history coupled with demographics, such as sex, age and education, have been shown to improve prognostic risk-stratification for persistent symptoms. Nevertheless, in adolescents, there is a lack of information about the biological mechanisms that underlie outcome, and measures such as blood protein levels, neuroimaging, or ocular motor function, etc. that may improve prognostication for and monitoring of recovery from persistent concussion symptoms. Persistent concussive symptoms often result in decreased academic performance and can lead to reduced quality of life. Because clinicians generally diagnose concussion and monitor recovery from concussion primarily based on self-reporting of symptoms, younger patients present a particular challenge in that they may lack proper insight and communication skills to reliably report their symptoms. This dilemma reinforces the need for objective biological measures that accurately reflect concussion symptoms and degrees of recovery. Moreover, the lack of well-defined biologic mechanisms, and validated biological measures for prognosing and monitoring persistent concussive symptoms hampers the development and selection of appropriate therapies and treatment. Current TBI research initiatives that focus on providing insight into the acute and subsequent course of recovery from concussion have not concentrated on peri-adolescent populations. Consequently, little is known about the acute and persistent effects of concussion in this age group.

In October 2016, NIH convened TBI researchers, experts on brain development, clinicians who treat pediatric concussion, and patient advocates to discuss pediatric concussion. The deliberations focused on the state of the science, the adequacy of current diagnostic tools and treatments, ongoing research supported by the NIH and CIHR, and feasible study designs to address major gaps in knowledge. Workshop attendees agreed that objective measures are needed to improve the prognosis and recovery monitoring of pediatric presenting with concussion and/or persistent concussive symptoms. Ultimately, these objective measures would be included in a risk stratification model for persistent concussive symptoms that will enhance clinical care and improve patient stratification for future clinical trials. To accomplish this goal, the Stakeholders recommended the collection of a dataset that will provide phenotypic, biological, and clinical data across the course of injury in an early adolescent population. Moreover, workshop participants suggested that this dataset should leverage the active NIH Adolescent Brain Cognitive Development (ABCD) study and other large TBI observational studies by harmonizing data collection protocols and implementing an accelerated data sharing plan when appropriate.

CIHR-INMHA Parallel Funding Opportunity:

The Canadian Institutes of Health Research - Institute of Neurosciences, Mental Health and Addiction (CIHR-INMHA) will establish a parallel funding program to support a single research project conducted at Canadian research institutes or facilities by Canadian investigators, within the PCS-EMA CWOW selected for funding by NINDS. CIHR-INMHA funding is expected to supplant the equivalent amount of funds from the PCS-EMA CWOW’s award budget provided by NIH and will not change the total amount of direct costs available. This funding opportunity will be published on the CIHR website.

To participate in the CIHR-INMHA parallel funding opportunity, applications to this FOA with a Canadian-based research component must also submit a parallel abbreviated application to CIHR-INMHA that details the requested support for the Canadian component of the PCS-EMA CWOW (see the CIHR website for details). The Canadian component must be an integrated part of the Research Project in an application to this FOA. All PCS-EMA CWOW applications, with or without a Canadian Component, will be reviewed using a standard NIH panel review process. As such, each PCS-EMA CWOW application will be reviewed in accordance with the review criteria outlined in Section V. Funds from CIHR-INMHA will only be applicable to the CWOW selected for funding by NINDS and. To the extent permissible under applicable laws, regulations and policies, this Canadian research team is expected to function and participate in all of the PCS-EMA CWOW activities, including involvement in the CWOW’s leadership committees and teleconferences, annual and semi-annual meetings, publications, and any additional PCS-EMA CWOW endeavors.

Specific Research Objectives

This FOA solicits multicenter applications from multidisciplinary groups in order to develop, and then perform an initial clinical validation of objective biological measures to improve accuracy for prognosticating and / or monitoring persistent concussive symptoms that result from concussion and/or repetitive head impacts in adolescent populations. The overarching goal of this program is to develop and validate biological measures that will improve prognosis of persistent concussive symptoms in EMA patients that accounts for and is sensitive to individual variability of symptom presentation. The scientific project must include three parts: 1) a development phase, 2) an initial clinical validation phase, and 3) a description of how the validated biological measures will be incorporated into a risk stratification algorithm for persistent concussive symptoms. Development phase: In the development stage, the research project should focus on determining the sensitivity and specificity of one or more biological measures for prognosing and/or monitoring persistent concussive symptoms in an EMA population. Where feasible, each biological measure should be collected across all research sites. Initial clinical validation phase: A new independent cohort must be recruited and tested with the full set of biological measurements to be validated using the parameters and context of use obtained in the development phase.

For this FOA, the "initial clinical validation" phase refers to the evaluation of each individual and/or set of biological measures in a newly recruited cohort (independent of those participating in the development phase) to: (1) establish that the biological measure(s) acceptably prognose persistent concussive symptoms in the EMA population. Including a statement that fully and clearly describes the context under which the biological measure(s) will have prognostic value. The description of the context should include but is not limited to: the point of care, clinical presentation of the population (e.g. patient groups with specific concussive symptom clusters), and mechanism of injury; (2) develop a clinically useful risk stratification algorithm that incorporates these biological measures with current clinical and self-report measures (e.g., The Rivermead Postconcussive Symptom Questionnaire, Pediatric Quality of Life Inventory, or Post-Concussion Symptom Inventory for Children). The PCS-EMA CWOW must also provide the broader scientific community with a data resource for hypothesis generation, test validation, and discovery related to pediatric concussion using data sharing through the Federal Interagency TBI Research (FITBIR) (https://fitbir.nih.gov/) database and the NINDS biomarker repository, BioSEND (https://www.biosend.org/).

Specific Areas of Research Interest

Applications to this FOA will be expected to work synergistically to develop, characterize, and perform an initial clinical validation of a biological measure or combination of biological measures for prognosis and/or monitoring recovery of persistent concussive symptoms with enrollment from multiple points of care (e.g., Emergency Departments, urgent care clinics, primary care, concussion/sports medicine clinics, or other specialty clinics) and participants with a variety of injury mechanisms (e.g., falls, sports, abusive head trauma, automobile accidents). The application may include established biological measures with an existing body of literature supporting their use for prognosing persistent concussive-symptoms and/or the discovery of novel (less developed) candidate biological measures for persistent concussive-symptoms. The feasibility of using the proposed biological measure(s) in clinical settings and future clinical trials should be considered. Biological measures that are responsive may include, but are not limited to, neuroimaging, electroencephalography, oculomotor control, vestibular function, measures of auditory processing and speech production, autonomic responses, metabolomics, proteomics and other biofluid-based assays. The biological mechanism of action for each biological measurement is not required to be known, although it may be advantageous. The applications' analysis plans are also expected to include potential mediating factors such as medication and the type and amount of post-injury treatment and rehabilitation provided to participants.

The scientific project must include both a Development phase and an Initial clinical validation phase to the project. Clinically validated measures should then be incorporated into a clinical risk stratification algorithm for persistent concussive symptoms in early and middle adolescent (EMA) populations.

Examples of clinical research designs that would be appropriate under this FOA should include, but are not limited to:

• A well-phenotyped prospective cohort study using EMA persons presenting with acute injury and those presenting with persistent concussive symptoms.
• A Cross-Sequential study design using EMA persons presenting with acute injury and those presenting with persistent concussive symptoms.

Non-responsive studies include:

• Use of pre-injury prospective designs that rely on concussion incidence rates as the source of recruiting acutely injured participants.
• Studies limited to only one injury mechanism (e.g. sports-related concussion) or limited to a single point of care (e.g., recruitment only in emergency departments).
• Clinical Efficacy trials assessing multiple post-injury treatment protocols.
• Preclinical research studies using animal models of TBI and PCS.

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. PCS-EMA CWOW applications deemed not responsive to the FOA will be withdrawn.

Common Data Element Use and Data Sharing

It is expected that the PCS-EMA CWOW will incorporate the NINDS Core TBI pediatric common data elements (CDEs) and appropriate Core CDEs in the NINDS TBI CDE set.

Additionally, studies are required 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.

In order to advance the goal of widespread data sharing, investigators funded under this FOA are required to share all data collected in this FOA via FITBIR. FITBIR staff will work with investigators to help them submit data types consistent with the FITBIR Data Dictionary and the NINDS CDE program. 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, the PCS-EMA CWOW will be required to share a "limited" clinical dataset (e.g., clinical assessment & outcome measures, symptom lists, mechanism of injury, demographics, etc.), excluding biological measures, in a FITBIR limited-access "public state no more than 1-year after collection.

Biological Samples

All biological specimens are required to be banked at the NINDS BioSEND Biomarkers Repository. When appropriate, biospecimens must be collected per NINDS Biomarkers Repository protocols and procedures, and all specimens collected 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 Biomarkers Repository award. Therefore, most costs for the biospecimen banking are borne by the grantees utilizing this resource (see NOT-NS-15-046) and should be budgeted for in the application. Applicants planning projects in which biospecimens will be collected are strongly advised to consult the NINDS Biomarkers Repository website for more information about samples banked at the repository (https://www.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]).

Imaging Based Studies

For applications proposing to include neuroimaging, the NINDS neuroimaging CDEs and imaging protocols should, as much as possible, align with existing large federally-funded TBI and/or adolescent cohort studies (e.g., TRACK-TBI ; NCAA/DoD CARE Consortium, Chronic Effects of Neurotrauma Consortium, NIH's Adolescent Brain Cognitive Development Study (ABCD)). Further, when incorporating neuroimaging methods, consideration should be taken regarding the feasibility of carrying out the proposed methods in a non-research environment (e.g., non-academic hospitals).

Required components:

Each application must have an Administrative Core, a Data Coordinating Research Core, and a single Research Project. The Research Project must utilize the cores within the PCS-EMA CWOW.

Administrative Core: The Program Director(s)/Principal Investigators (PD/PIs) should serve as the lead(s) of this Core. The Administrative Core should coordinate the integration and management of activities within the Center including management of reporting, establishing milestones, organizing communications among sites, and resolving disputes.

Data Coordinating Core: The Data Coordinating Core (DCC) must provide a data management plan capable of coordinating and curating data collected across all PCS-EMA CWOW research projects. The DCC will be responsible for data submission to the FITBIR informatics platform and be able to coordinate with the NINDS biomarker repository, BioSEND. The end goal of the data management plan should be to develop a resource of clinical, neuroimaging, behavioral, and biological data for the broader scientific community.

Research Project: A single research project to address the list of research areas of interest. In the development phase, the research project should focus on the development of and determining the selectivity and specificity of a unique individual or set of biological measures.

The analysis at this phase should inform the context(s) under which the biological measure(s) could be used in the initial clinical validation phase (e.g. point of care, patient sub-groups with specific concussive symptom clusters, and/or mechanism of injury). Where feasible, each biological measure should be collected across all research sites. For the initial clinical validation phase, each research site should collect the full set of biological measures to be validated. The initial clinical validation phase must be conducted in a newly recruited cohort that is independent of the cohort recruited in the developmental phase. Following the initial clinical validation, a risk stratification algorithm for prognosing and/or monitoring recovery of persistent concussive symptoms in an adolescent population should be developed. If necessary, the research project may require Research Cores for specific biological measurements being collected.

Milestones: Milestones are required for the CWOW and must address data sharing progress with FITBIR as described in NOT-NS-17-029 and, if applicable, with BioSEND. Applicants should propose annual milestones that provide clear go/no-go decision points for evaluating the project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Achievement of milestones will be evaluated by NINDS Program staff, and funding of non-competing award years will depend on milestone accomplishments. Milestones should also include clear quantitative thresholds for determining whether specific or a combination of biological measures will move on from the development phase to the initial clinical validation phase.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

The letter of intent should be sent to:

Patrick SF Bellgowan, PhD
Telephone: 301-496-1447
Fax: 301-480-1080
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	6
Admin Core	6
Data Coordinating Core	6
Research Core	6
Research Project	12

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

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

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Data Coordinating Core: required, maximum of 1
• Research Cores: optional, maximum of 3
• Research Project: required, maximum of 1

When preparing your application, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

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

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

Budget considerations should include, but are not limited to:

• Estimated costs per year for clinical, neuroimaging, and physiological data curation and data sharing through FITBIR.
• Estimated costs per year for biospecimen storage at the NINDS BioSEND biospecimen repository

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

Specific Aims: The specific aims should outline the overall vision and scientific strategy of the PCS-EMA CWOW. The Aims should be overarching and at a high level distinct from the Aims of individual Cores and Research Project. The Aims must address the rationale for the selected biological measures as predictors of persistent concussive symptoms in this EMA population and specify the potential use(s) of the proposed biological measure(s) as it relates to contextual factors such as injury type, time since injury, and / or point of care. Aims must address how the biological measures would be integrated into a risk stratification algorithm.

Research Strategy: The Overall Research Strategy should describe the PCS-EMA CWOW's goals and objectives, background information, and the overall importance of including biological measures into the prognosis and monitoring of persistent concussive symptoms in an adolescent population. Describe the rationale for the proposed program and how each site is uniquely positioned to contribute world-class expertise and cutting-edge resources towards addressing the aims. Describe the rationale for choosing the biological measure of combination of biological measures including their feasibility for use in clinical settings and future clinical trials. Describe the need for any proposed research cores and how they will interact with the projects and the Administrative core. Explain the strategy for achieving the goals defined for the overall Center, how the research project and research cores relate to that strategy, and a transition plan for moving from the development phase to the initial clinical validation of the biological measures to a risk stratification algorithm. Clearly describe the context(s) under which the biological measure(s) could be used. The context(s) description should include but is not limited to: the point of care, clinical presentation of the population (e.g. patient groups with specific concussive symptom clusters), and mechanism of injury. The biological measures and risk stratification algorithm should be practical, efficient, and implementable in the appropriate clinical settings where patients present; e.g., emergency departments, urgent care clinics, sports medicine clinics, and primary care offices. Describe the plan for developing to a resource for the broader research community including policies for access and collaborations. Describe how the data sharing resource developed in this Center will serve to accelerate research and knowledge about persistent concussive symptoms in adolescents.

Study Leadership and Management: This may be either a single or multiple PD/PI project. Multiple PD/PI projects must provide a Study Leadership and Management section that should include the overall study leadership structure. A description of the research team and a plan to ensure the maintenance of close collaboration and effective communication among members of the research team. The steps that will be taken to ensure successful completion of the research proposed should be described, in the event that a key member leaves the project prior to the end of the performance period.

Milestones: A milestone plan, under separate headings, must be included in the Research Strategy section of the application. Milestones are goals that create go/no-go decision points in the CWOW and must include clear and quantitative criteria for success. Milestones must assess the overall performance of the proposed cores and include clear and quantitative criteria for success. The milestone plan must include a timeline for recruitment and number of visits per year over the course of the study and a data sharing schedule that is consistent with NINDS's TBI data submission policy NOT-NS-17-029.

Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, consultants, and / or BioSEND if biospecimen are being collected. Letters of support for the Center overall should be included with the Overall component. Letters of support for individual scientific projects or cores should be included with those components of the application.

Collaboration with NIH Intramural Researchers:

A letter from the Scientific Director of the collaborating NIH Institute or Center must be submitted as part of the Center application and must specify the amount of NIH Intramural resources to be allocated to the proposed project. In addition, the letter should state that the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research (if applicable).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the modifications indicated in the Data Sharing Plan section above.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

When preparing your application, use Component Type Administrative Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

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

Specific Aims: Describe the aims for ensuring that the overall vision of the proposed Consortium is achieved. Hypothesis-driven research aims are not appropriate.

Research Strategy: Without duplicating information in the biosketch, the Administrative Core Lead should describe their research productivity, active research funding (NIH R01-equivalent or greater) at time of submission, and capacity for visionary leadership of an interdisciplinary 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 Administrative Core personnel including scientific leadership, and administrative management and coordination of the proposed activities. Plans for holding regular meetings and facilitating communication between the project and cores; prioritizing core and 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. Describe the plan to develop policies and procedures for providing access to data from both key investigators and potential collaborators from outside the Center. Provide a description of the "limited" clinical data set (e.g., clinical assessment & outcome measures, symptom lists, mechanism of injury, demographics, etc.) to be available in FITBIR in a limited access "public state no more than 1-year after collection. The administrative core should provide training across research sites for clinical assessment batteries and biological sample collection. An annual in-person center meeting is strongly encouraged.

Letters of Support: When appropriate, a letter of support should be provided from BioSEND that demonstrates the Administrative Core has contacted and received a cost estimate for BioSEND's services

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.

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Consistent with achieving the goals of the program, plans for developing a publicly available dataset, including a description of the components of a limited dataset that will be shared on an annual basis, are expected to be described.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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

When preparing your application in ASSIST, use Component Type 'Data Coordinating Core.'

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

SF424 (R&R) Cover (Data Coordinating Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Data Coordinating Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Coordinating Core)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

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

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

Project /Performance Site Location(s) (Data Coordinating Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Data Coordinating Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Coordinating Core)

Budget forms appropriate for the specific component will be included in the application package. This level of effort is required whether or not salary is requested.

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

PHS 398 Research Plan (Data Coordinating Core)

Specific Aims: Describe the aims for providing the necessary resources and technical expertise to support the goals of the research project and support both the coordination of specimen collection and storage with BioSEND and data sharing requirements of the PCS-EMAs CWOW related to FITBIR data submission, data curation, and data quality assurance. Hypothesis-driven research aims are not appropriate.

Research Strategy: Each application should detail the core service to be provided, including all equipment, methods, or services involved. Describe all aspects of the core resource that are innovative, and any technical or methodological innovations that will be developed during the duration of the project. Applicants should explain how this core will interact with the research project and other cores within the Center. The Data Coordinating Core should demonstrate knowledge of and provide methods for complying with the data and specimen submission policies of FITBIR and BioSEND. Data quality assurance of data submitted to FITBIR is the responsibility of the DCC. Applications should describe the data quality assurance procedures that will be implemented. Multi-site grants must include description of inter-site data quality assurance, including protocols for corrective actions when needed. Describe the site-specific and centralized data management, harmonization and curation plan.

The Data Coordinating Core is responsible for providing a thorough list of all CDEs and Unique Data Elements (UDEs) that will be collected in all projects.

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 DCC must develop a policy and standard operating procedure that outlines the processes required to make raw and analyzed data available to Center investigators and, when appropriate, to external collaboration requestors.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Data Coordinating Core)

When involving NIH-defined human subjects research, clinical research, and/or 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

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

When preparing your application in ASSIST, use Component Type 'Research Core.'

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

SF424 (R&R) Cover (Research Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Core)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

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

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

Project /Performance Site Location(s) (Research Core)

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Core)

Budget forms appropriate for the specific component will be included in the application package. This level of effort is required whether or not salary is requested.

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

PHS 398 Research Plan (Research Core)

Specific Aims: Describe the aims for providing the necessary resources and technical expertise to support the goals of the research project and the overall PCS-EMA CWOW. Hypothesis-driven research aims are not appropriate.

Research Strategy: Each application should detail the core service to be provided, including all equipment, methods, or services involved. Describe all aspects of the core resource that are innovative, and any technical or methodological innovations that will be developed during the duration of the project. Applicants should explain how this core will interact with the research project and other cores within the Center. If a core is collecting or providing specimens, collection and storage protocols should be clearly described and standardized across collection sites. If a core is developing new analytic protocols, methods, tools, and /or analytic pipelines there must be a plan to share or distribute them to the broader research community; consistent with the data sharing goals of this FOA.

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.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Core)

When involving NIH-defined human subjects research, clinical research, and/or 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

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

When preparing your application in ASSIST, use Component Type 'Project'

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

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

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

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Project)

Budget forms appropriate for the specific component will be included in the application package. The amount of effort for the Project Leadmust be commensurate with the requirements of the position. This level of effort is required whether or not salary is requested.

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

PHS 398 Research Plan (Research Project)

Specific Aims: Provide the overall goals or hypothesis of the entire research project and list separate Specific Aims to be accomplished, briefly outline the methods proposed, and summarize the expected outcomes. Within the Specific Aims section, include headers titled Developmental Phase Specific Aims and Initial Clinical Validation Phase Specific Aims. Under each header, state the specific hypotheses and goals of that phase.

Research Strategy: Describe the research strategy for the project and how the research will develop and then characterize the selectivity and sensitivity of biological measure(s) for either prognosing and/or monitoring persistent concussive symptoms in an EMA population. 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 rigor of prior research, scientific rigor, and biological variables). Provide alternative approaches to addressing the research aims if the proposed approaches fail. If research cores are being proposed, applicants should explain how this research project will interact and synergize with the research cores within the CWOW. Analysis plans are expected to include potential mediating factors such as medication and the type and amount of post-injury treatment and rehabilitation provided to participants. Provide clear diagnostic criteria used in the project for clinical presentation including, but not limited to, diagnostic criteria for concussion, mild TBI, and persistent concussive symptoms. Describe the process for selecting the clinical data that will included in the risk stratification algorithm that incorporates the biological measures.

Enrollment:

Enrollment during both the development and initial clinical validation phases must only include early and middle adolescent (EMA; 11 - 17 years old) aged persons (as defined by the American Academy of Pediatrics Bright Futures Guidelines) at initial enrollment with a sampling strategy designed to establish a cohort that is broadly representative of and generalizable to a North American general population, including males and females, as well as major racial, ethnic, and sociodemographic subgroups of the population. Detailed plans for ensuring high rates of recruitment and retention should be described. The enrollment plan must include enrollment from multiple, diverse, clinical settings (e.g., emergency departments, urgent care clinics, sports medicine clinics, and primary care offices) and include representation of multiple injury mechanisms.

Use of standardized outcome and non-outcome measures and instruments (e.g., NINDS Common Data Elements (CDEs)) that are compatible with existing natural history and comparative effectiveness trials of TBI and/or neurodevelopment studies (TRACK-TBI, ADAPT, and ABCD study) is highly recommended. Justification must be provided for using measures and instruments that are Unique Data Elements (UDEs); i.e. not NINDS CDEs. When appropriate, clear operational definitions for independent and dependent measures such as "repetitive head hits", "impacts" and "concussion" should be provided.

Description must include analytic plans for determining the sensitivity and specificity of each measure and any combination of measures, interim analysis for biological measures including alternative strategies, and for the selection of biological measures that will be advanced to the initial clinical validation phase.

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.

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.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

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 Center 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 Center 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 Center that by its nature is not innovative may be essential to advance a field.

Does the Center 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 Center 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? Does the PCS-EMAs CWOW's selection of biological measures appropriately cover the diversity of symptom clusters present in EMA patients with persistent concussive symptoms? If the aims of the PCS-EMAs CWOW are achieved, are the resultant biological measures feasible for use in clinical settings and in future clinical trials? If the aims of the PCS-EMS's CWOW are achieved, will the risk stratification algorithm be practical, efficient and implementable in clinical settings?

Will the proposed data sharing resource serve to accelerate research and knowledge in the area of persistent concussive symptoms in adolescents?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? 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 application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application propose methods to assess the diversity of symptom presentation of persistent-concussive symptoms in the EMA population? Does the application apply innovative methods, technology, and approaches to accelerate research in this area to develop a data resource for the broader community?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Have 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 Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

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

Is there a clear and objective plan for transitioning the biological measures from the development phase to the initial clinical validation phase? Is there a clear description of the context(s) in which the biological measure(s) will have utility? Is there a clear plan for developing a data resource for the broader research community?

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

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

Administrative Core

Does the Administrative Core provide support such that overall vision of the proposed CWOW is achieved? Does the Administrative Core Lead/Center Director have appropriate expertise and dedicate enough time to administrative activities? If an Associate Director is named, does that person have required expertise to effectively assist the Center Director with scientific and administrative management? Is there an appropriate plan for establishing and maintaining effective communications and cooperation among Center investigators on a regular basis? Does the core 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? Are plans included for prioritizing how core resources will be utilized? Are there appropriate plans for management of data, specimens, and other resources? Is the leadership approach, governance and organizational structure appropriate for the project? Does the core provide clear and quantifiable milestones creating go/no-go decision points for measuring the success of its goals?

Has the Administrative Core demonstrated a commitment to the principle of data sharing and developing a data resource for the broader research community? Has the Core described the data that will be included in the "limited dataset" that will be uploaded to FITBIR and shared on an annual basis?

Data Coordinating Core

Does the proposed data coordinating core have the equipment, methods, and/or services appropriate for managing, curating, analyzing and sharing data from each project?

Are the data curation and validation methods scientifically rigorous?

Are any technological or methodological innovations proposed?

Does the core Leader/Director have the appropriate expertise and enough dedicated time to direct and fulfill the core activities? Does the administrative core provide a training plan to standardize data collection across research sites for clinical assessment batteries and biological sample collection? Has the core demonstrated an understanding of the FITBIR and BioSEND data policies and procedures? Has the core provided an estimate from BioSEND for sample collection and storage? Has the DCC provided a list of all CDEs and UDEs used by the Research Projects and justified the use of UDEs? Does the core provide methods for cross-mapping the Centers data dictionary to the existing NINDS CDEs? Are clear and quantifiable milestones creating go/no-go decision points for measuring the success of all the core's aims provided? Has the core provided a plan for submission of all relevant data to FITBIR?

Research Core

Is the proposed core scientifically justified in the context of the CWOW's overall goal? Are all equipment, methods, and/or services state-of-the-art, clearly described, appropriate for addressing the CWOW's hypotheses, and scientifically rigorous? Are any technological or methodological innovations proposed?

Does the core Leader/Director have the appropriate expertise and dedicate sufficient time to core activities?

Does the core provide essential support, resources, and expertise to the research project within the CWOW?

If the proposed core is developing new analytic protocols, methods, tools, and / or analytic pipelines, is there a plan to share these broadly?

Scored Review Criteria - Research Project

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 Research Project that by its nature is not innovative may be essential to advance a field or the overall goals of the Center. Reviewers will consider each of the review criteria below in the determination of scientific merit:

Significance

Does the research 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 research 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?

Do the project's aims/hypotheses address an important aspect of the Center's overall strategy for incorporating biological measures to address prognosis and/or monitoring of persistent concussive symptoms in pediatric populations and integrating those measures into a prognostic algorithm?

Is the project likely to result in major scientific advances in the prognosis of persistent concussive symptoms?

Investigator(s)

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

Are the Project Lead(s), collaborators, and other researchers well suited to the purpose of developing and validating biological measures for prognosis and / or monitoring of persistent concussive symptoms)?

Is the research project leader an established scientist with a history of innovative work in their area of research?

Do all members of the project team dedicate sufficient effort to research activities?

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?

Does the research project propose innovative use of the biological measure(s) in its approach to addressing its hypotheses? (e.g. Has this biological measure been used in an EMA population for prognosing persistent concussive symptoms? Is this biological measure being collected in an innovative context (time and / or place)?

Does the research project propose an innovative method for determining the specificity of the biological measure(s)?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the research project? Have 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 research 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 PCS-EMA CWOW have a clear and justified operational definition of "Persistent Concussive Symptoms"?

Have the investigators presented adequate plans to address relevant biological variables?

Is a feasible plan provided to recruit and retain EMA pediatric participants for both the development and the initial clinical validation stages?

Is there a plan for recruiting that ensures recruitment from diverse clinical settings where patients present; e.g., emergency departments, urgent care clinics, sports medicine clinics, and primary care offices?

Have the investigators provided a recruitment plan to establish cohorts that are broadly representative of and generalizable to the pre-adolescent and adolescent North American population?

Does the application provide clear diagnostic criteria for concussion, mild TBI, and moderate TBI?

Does the PCS-EMA CWOW have consistent definitions for head impact, repetitive head impacts and / or TBI exposure?

Do the investigators incorporate the NINDS CDEs and align with natural history and comparative effectiveness trials of TBI and/or neurodevelopment studies when appropriate?

Does the project clearly detail the development and initial clinical validation of one or more biological measures that will have a significant impact on the prognostic and monitoring accuracy of persistent concussive symptoms following either concussion and/or exposure to repetitive head impacts?

Does the application include an analytic plan for determining the sensitivity and specificity of biological measures?

Does the analysis plan account for potential mediating factors such as medication and the type and amount of post-injury treatment and rehabilitation provided to participants?

Is there a clear strategy for inclusion of the biological measure(s) into the development of the risk stratification algorithm?

Is there a clear description of how this research project will interact and synergize with the cores within the Center?

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?

Do the study environments provide a range of point of care settings?

Will recruitment include patients with a range of injury mechanisms (e.g. falls, sports, and automobile accidents)?

As applicable for the Center 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.

Milestones

Are the milestones appropriate to the scientific aims of the project? Do the milestones provide enough timeline details and quantification of subject recruitment and retention? Does the recruitment timeline provide alternative strategies if recruitment and retention are lower than expected? Do the milestones provide objective measures for go/no go programmatic decisions? Are the milestones feasible within the timeline presented? Is the data sharing plan achievable? Do the milestones provide timelines for uploading the "limited dataset" into FITBIR? Do the milestones provide timelines and quantities of the full data set to be uploaded into FITBIR?

Interaction

Are there adequate plans for ensuring effective intra-group communication, interaction, cohesiveness, and coordination among the PD(s)/PI(s), Research Project Leaders, and NINDS Project Scientist? Are there plans for scheduling group meetings, notifying group members (including NINDS Scientific and Program Officers), and documenting and disseminating group meeting proceedings?

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

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

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

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

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

Not Applicable.

Not Applicable

Not Applicable.

As applicable for the 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.

Not Applicable.

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the the National Advisory Neurological Disorders and Stroke (NANDS) Council. The following will be considered in making funding decisions:

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

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

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

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

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

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

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

• Determining experimental approaches, designing protocols, setting project milestones and conducting experiments;
• Developing policies regarding data sharing, CDE usage and protocol alignment with existing TBI and neurodevelopmental consortia;
• Reporting to NINDS Scientific Program staff regarding timeline and milestone achievement during the course of the project, as delineated in the terms and conditions of award;
• Submitting annual progress reports during the funding period, in a format as agreed upon by NINDS program staff;
• Awardees are expected to make new information and materials known to the research community not only in the annual meetings but also in a timely manner through publications, web announcements, reports to NINDS program staff, and other mechanisms.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

Publications:

The PD(s)/PI(s) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit manuscripts to the NIH Project Scientists within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Project Leaders and will require appropriate acknowledgement of NINDS support. Timely publication of major findings is required.

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

• An NINDS Scientific Program Official will be assigned and will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Scientific Program Officer will be to facilitate and not to direct the activities.
• The NINDS Scientific Program Official will contribute to the adjustment of research protocols, project milestones or approaches as warranted;
• NINDS Scientific Program Official may serve as a liaison between the awardees, the NINDS Advisory Council and the larger scientific community;
• NINDS Scientific Program Official will assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• NINDS Scientific Program Official will assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• A separate NINDS Administrative Program Official will retain the option to 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.
• Additionally, the NINDS Administrative Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

None; all responsibilities are divided between awardees and NIH staff as described above.

Opportunities for Partnership

Projects involving partnerships with industry, small businesses or non-government organizations are encouraged under this FOA. The policy of the NIH is to make available to the public the results and accomplishments of the activities that it funds. To ensure that research resources are made accessible to the broader biomedical community, NIH expects applicants who respond to this funding opportunity to submit a plan for: (1) sharing the research resources generated through any grants awarded and (2) addressing how they will exercise intellectual property rights, should any be generated through an award, while making such research resources available to the broader scientific community consistent with this initiative. Projects existing studies in which databases already exist or have been created via other resources may be maintained under those projects, but not funded via this program. However, it is expected that these databases will become federated under the DMR.

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 Administrative Core 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16

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

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

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

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

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

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

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Patrick SF Bellgowan, Ph.D.
Repair and Plasticity Cluster, National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email: [email protected]

Natalia Strunnikova, Ph.D
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]

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

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.