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

Background

Recent clinical trials in neurotrauma, including traumatic brain injury (TBI) and spinal cord injury (SCI) have failed to demonstrate therapeutic effects even when there appears to be good evidence for efficacy in one or more appropriate preclinical models. In both SCI and TBI, the time and cause of the initial injury are typically known, but the resulting diagnosis and prognosis are difficult to predict due in part to the wide heterogeneity of the underlying damage and subsequent pathological processes. While existing animal models mimic the injury causes, difficulties in translating promising therapeutics are exacerbated by the lack of alignment of discrete measures of the underlying injury pathology between the animal models and human subjects. Translational activities in this area have been largely dependent on gross behavioral tests and outcomes of efficacy that correlate with injury severity in the animal models but do not mimic practical and objective clinical measures of the underlying pathology that could facilitate patient selection or stratification for clinical trial design.

Purpose

To address this mismatch, NINDS is seeking multi-disciplinary teams of preclinical and clinical researchers to identify and develop new measures of discrete neurological function in preclinical models that are reliable and have relevant and practical correlates for clinical assessment in TBI and/or SCI. This initiative is intended to (1) facilitate the development of sensitive preclinical outcome measures or functional biomarkers that reflect and predict underlying pathophysiological mechanisms, (2) incorporate reverse translation of bedside experience to inform preclinical measures that mirror practical clinical assessments, and (3) support quality data sharing initiatives across the TBI and SCI fields to improve reproducibility and inform advancements in preclinical studies and clinical trial design.

Researchers are invited to define and test mechanistically driven assessment batteries for preclinical research that are sensitive, selective, robust and accurate for determining the location, type, and extent of the underlying pathology. Examples of measures might include, but are not limited to, functional markers of: white matter integrity, axonal continuity or synaptic connectivity, vascular function or status, inflammatory sites or status, or other pathological events that would distinguish among heterogeneous injury types in a blinded fashion. Multidisciplinary approaches may include, but are not limited to, combinations of electrophysiology, imaging, biochemical analyses, or discrete measures of sensory, motor, autonomic or higher functions. Active participation and input from clinical experts is required. Importantly, the assessments should extend beyond markers correlated only with injury severity. To ensure maximal value of the project, the research data should be collected in a manner that is compliant with the 'FAIR Data Principles', which are endorsed by the NIH Commons Framework so that the resulting data is Findable, Accessible, Interoperable and Reusable, and will be readily shared with the research community.

The UG3 Phase

The UG3 Phase is required, and will support initial development and internal validation of an assessment battery that can distinguish two or more underlying injury pathological processes. The research plan should incorporate a longitudinal analysis of changes and variability in these measures over time and discuss approaches to ensure quality data collection and data sharing principles. Study considerations for the UG3 phase should include:

• Use of two or more approaches to distinguish different pathological processes in blinded analyses.
• Evidence demonstrating feasibility and proof of concept for the proposed approaches.
• Identification of key metadata to be collected to enable reproducibility.
• Quantitative and statistical methods to assess sensitivity, specificity, variability and reliability across injury types and over time.
• Development and testing protocols and methods that are transportable to other researchers.
• Incorporation of clinical expertise in selection of relevant and practical outcome measures.
• Measurable milestones and decision points for transition to external validation steps in the UH3 Phase.

The UH3 Phase

The UH3 Phase will support collaboration and cross validation of the assessment battery across sites to expand to additional injury models, species and research sites and incorporate data collection and sharing activities to provide resources for other researchers. Functional validation study approaches for the UH3 phase should include, but are not limited to:

• Description of the anticipated selectivity for injury types and recommended time points for use of measures and assessment battery.
• Approaches to evaluate the sensitivity and reliability of the measures and assessment battery across additional injury models and conditions.
• Description of approaches to share and transfer the procedures, provide training, and evaluate reproducibility at other sites.
• Approaches to collect and share data according to FAIR Data principles.

UG3/UH3 Transition Milestones

Transition from the UG3 to the UH3 phase of the project will be dependent upon meeting required objective transition milestones during the UG3 phase. Transition milestones should include three basic components: 1) Rationale, 2) Measurable Deliverables, and 3) Criteria for Success.

Studies not responsive under this FOA:

• While consultation and collaboration with clinical experts is required, human subjects research including clinical case studies, studies requiring collection of clinical samples, or studies requiring testing on human subjects are not responsive to this FOA. However, validation of relevance with existing clinical datasets may be included. NINDS Clinical Research Resources can be found at: https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Clinical-Research
• Clinical trials are not allowed under this FOA.
• While interventions may be included for validation tests, studies designed primarily to develop or test the effectiveness of interventions in preclinical models are not responsive. Studies designed to optimize the pharmacodynamics or pharmacokinetics of an intervention, to inform design of an interventional device, and/or to test efficacy of a surgical procedure or rehabilitation strategy are not responsive to this FOA. Investigators exploring therapeutic translational projects should consider the NINDS Translational Research Funding Opportunities.
• Studies that include development of new SCI or TBI models are not responsive to this FOA.
• Investigators are encouraged to contact the program officers listed at the end of this announcement for further guidance.

TOP-NT Consortium

In collaboration with NIH program staff, grants awarded under this FOA will function as a Consortium to develop shared strategies for: 1) testing and external validation of sensitive and selective preclinical assessment batteries that distinguish types of injury based on underlying pathophysiology, 2) incorporation of clinical consultation at all stages of the project to ensure that the preclinical measures have clinical relevance and that translation to the clinical setting is feasible and practical, 3) development of an interoperable data and analytical platform for neurotrauma researchers, 4) external validation of outcome batteries for use at different research sites, and 5) refinement of approaches and test cases to augment the translational pipeline in neurotrauma.

The overall outcome of TOP-NT Consortium will be a coordinated validation and data sharing effort for neurotrauma preclinical measures; where methods, protocols, and representative data analysis approaches result in improved alignment of preclinical and clinical assessments, and plans for data sharing ensure access of representative datasets for the broad neurotrauma research community. An external liaison committee will be identified by the Consortium investigators and NIH representatives early during the UG3 Phase.  The external liaison committee will be charged with providing expert knowledge and support to refine strategies to be applied in the UH3 Phase. A face to face meeting will be held during the first quarter of the UG3 Phase to develop the Consortium governance and procedures.  Quarterly teleconferences will be held across the Consortium sites to review progress and address any roadblocks or delays that would impact the successful transition to the UH3 phase.  A second face to face meeting may be held with NIH staff and the external liaison committee three to four months prior to the UH3 transition. The Consortium will provide and refine as needed the final recommendations for common milestones to be applied in the UH3 Phase.

Applicants are strongly encouraged to consult with NINDS Scientific/Research Staff at the beginning of the planning stage of their application (see Agency contacts, Section VIII).

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 in response to 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Lyn. Jakeman
Telephone: 301-496-1447
Fax: 301-480-1080
Email: [email protected]

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

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

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

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

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

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

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

Budget considerations for the UG3 phase should include, but are not limited to:

• Estimated costs approximately $25,000 per year in the UG3 Phase for personnel time and IT support to assist in developing data collection methodology and preparation for sharing as defined by the TOP-NT Consortium.
• Travel costs for PDs/PIs and up to 2 research team members to attend 2 face to face meetings in the Washington, DC metropolitan area.

Budget consideration for UH3 should include, but are not limited to:

• Estimated costs approximately $50,000 per year in the UH3 Phase for personnel time and IT support to assist in data collection and authentication at the data entry site, and storage fees if required by the TOP-NT Consortium and applicable NINDS Contracts.
• Travel costs for PDs/PIs and up to 2 research team members to attend 1 face to face meeting per year in the Washington, DC metropolitan area.

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

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

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

Specific Aims:

• Provide the overall goals or hypotheses for the entire project period and identify separate Specific Aims to be accomplished in the UG3 phase and in the UH3 phase.

Research Strategy:

• Provide separate sections that describe both the UG3 and UH3 phases.
• Include a description of the premise for the chosen assessment battery, including the strengths and quality of the data used to provide the basis for the chosen measures.
• Provide a description of the test battery to be developed in the UG3 phase using two or more approaches to assess and distinguish at least two closely related neurotrauma conditions or pathological processes (e.g. primary contusion vs. axonal injury). Include description of the predicted context of use, including the types of injury pathology and anticipated time points of greatest relevance.
• Provide a discussion of feasibility, reliability and comparability to practical clinical assessments.
• Include descriptions of key metadata to be collected to enable reproducibility.
• Provide descriptions of the design and statistical approaches to be used to establish reproducibility and test internal and external validity of the outcome measures in the UG3 and UH3 Phases, respectively.
• Clinical research is not permitted. If reverse translational validation using existing datasets is proposed, include evidence of access to appropriate existing datasets and documentation that the database meets the requirements for Exemption 4 (E4) status.

Timeline and Milestones for transition to the UH3 phase must be provided in a separate heading within the Research Strategy:

• The Timeline and Transition Milestone Section should include a Timeline (Gantt chart) for major activities of both the UG3 and UH3 Phases with anticipated delivery dates for proposed activities.
• Activities in the UG3 Phase of the timeline should include, but are not limited to: initial development, testing, and internal replication of the outcomes battery in a blinded evaluation of sensitivity and reliability to distinguish pathology in two similar injury models (e.g. contusion vs axonal injury).
• Activities in the UH3 Phase of the timeline should include, but are not limited to: replication, external validation, extension to other models, and data sharing activities in collaboration with the TOP-NT Consortium.
• The Gantt chart should include estimated time points for clearly identified Go/No-Go Transition Milestones to be met during the UG3 Phase, for transition to the UH3 Phase.
• Transition Milestones should be described in text accompanying the timeline and should include 1) Rationale, 2) Measurable Deliverables, and 3) Criteria for Success. The Rationale will briefly describe the reason for selecting the milestone. The Measurable Deliverables should describe the quantitative measures of variability, sensitivity and reliability of the proposed assessments or functional markers based on valid statistical design. The Criteria for Success should state the minimal (quantitative) acceptable standards for a Go/No-Go decision for each milestone.

Additional Milestones are not required within either the UG3 or UH3 Phase. UH3 Phase Milestones will be established in collaboration with the TOP-NT Consortium and will be included in the UH3 Phase Notice of Award if continued.

Letters of Support:

Letters from named collaborators or consultants, indicating their specific role and level of commitment including agreement to participate in the TOP-NT Consortium in the UG3 and UH3 Phases.

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 following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Resource Sharing Plan.
• Applicants should anticipate that, if awarded, their project will join the TOP-NT Consortium, to identify consensus standards of practice and to aggregate data for access and dissemination among the wider scientific community. Accordingly, the Data Sharing Plan should include a statement of intention to join and cooperate with the TOP-NT Consortium and include: 1) Collection of data in compliance with FAIR Data Principles and including minimal reporting standards, and 2) Collaboration with TOP-NT consortium participants to make data and protocols developed in the course of the award available to the research community.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This UG3/UH3 phased innovation grant mechanism supports development and validation of pathophysiologically based preclinical measures and functional biomarkers that align with practical clinical assessments in SCI and/or TBI. The two Phases will have separate Specific Aims and be described in separate sections, but reviewers will consider the full Research Strategy and assign a single impact score for the entire application, which includes the UG3 and UH3 phases. The review criteria below correspond to specific application instructions in section IV.2.

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

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

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

Will the project lead to development of a reliable assessment battery that reflects clinically relevant measures of underlying pathology in TBI and/or SCI? Will the project lead to development of assessments that distinguish heterogeneous underlying pathological processes and will facilitate translation and clinical trial design?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Is the contribution of preclinical and clinical collaborators clearly described and appropriate for the proposed studies?

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

Are measures proposed that extend beyond assessments or markers correlated only with injury severity?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? 

• Is the project multidisciplinary, including two or more approaches to assess and distinguish at least two closely related neurotrauma conditions (e.g. contusion vs. axonal injury)?
• Does the outcomes battery reflect clinical assessments that would be feasible, reliable and comparable to practical clinical measures?
• Are the design and statistical approaches appropriate to establish reproducibility and measure variability and to test internal and external validity of the outcome measures in the UG3 and UH3 Phases?
• If reverse translational validation using existing datasets is proposed, is there evidence of access to appropriate existing datasets and documentation that the database meets the requirements for Exemption 4 (E4) status?

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

• Does the Timeline include appropriate steps and anticipated delivery dates for proposed activities in both the UG3 and UH3 Phases?
• Do the Transition Milestone reflect clear Go/No-Go decision points in the UG3 Phase for moving to the UH3 Phase? Do the Transition Milestones include 1) Rationale, 2) Measurable Outcome, and 3) Criteria for Success?

Not Applicable

Not applicable

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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 (GDS)

A Data Sharing Plan is required. The Data Sharing Plan should include a statement of intention to join and cooperate with the TOP-NT Consortium and include: 1) Collection of data in compliance with FAIR Data Principles and including minimal reporting standards, and 2) Collaboration with TOP-NT consortium participants to make data and protocols developed in the course of the award available to the research community.

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 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 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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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;
• Adhering to TOP-NT Consortium policies regarding data sharing and analysis, publication, and other policies that might be established during the course of this activity;
• 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;
• Accepting and implementing any other common guidelines and procedures developed for the TOP-NT Consortium;
• Attending in-person TOP-NT Consortium meetings to be organized in collaboration with NINDS program staff where PD(s)/PI(s) will present up to date findings (including unpublished results) on ongoing projects. The cost of attending these meetings will be covered under the current funding for this application.
• Complying with expectation 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 the TOP-NT Consortium sharing plan and 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, and will be responsible for:

NINDS Project Scientist Responsibilities:

• Providing scientific input to the project including, for example, technical assistance, advice and coordination. However, the role of NINDS Project Scientists will be to facilitate and not to direct the activities.
• Contributing to the adjustment of research protocols, project milestones or approaches as warranted;
• Serving as a liaison between the awardees, the National Advisory Neurological Disorders and Stroke (NANDS) Council, and the larger scientific community;
• Assisting in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• Assisting awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• NINDS staff 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.

In addition, an NINDS program official or NINDS Program Director 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.

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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual 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 progress report, 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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Lyn B. Jakeman, PhD
National Institute of Neurological Disorders and Stroke)
Telephone: 301-496-1447
Email: [email protected]

Patrick SF Bellgowan, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email: [email protected]

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

Tijuanna e. Decoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
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.