Required Application Instructions

It is critical that applicants follow the 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

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative is a Presidential project aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat, cure, and prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, BRAIN 2025: A Scientific Vision, which details seven high-priority research areas and calls for a sustained federal commitment of $4.5 billion over 12 years. This report can be found at http://braininitiative.nih.gov/. This FOA and other FOAs issued in Fiscal Year 2016 are based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group (http://www.braininitiative.nih.gov/BRAIN-MCWGroster-3.4.15.pdf), which held its second meeting on March 4, 2015 (see http://www.brainupdate.nih.gov/brain-research-through-advancing-neurotechnologies-insights-from-the-brain-initiative%e2%84%a0-multi-council-working-group/).

In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative (http://braininitiative.nih.gov/) support those research efforts through applications received via parent announcements as well as through specific funding opportunity announcements. Potential applicants to this FOA are strongly encouraged to contact Scientific/Research staff if they have any questions about the best funding opportunity announcement for their research.

To enable progress in development of new technologies as well as in theory and data analysis, the BRAIN Initiative encourages collaborations between neurobiologists and scientists from statistics, physics, mathematics, engineering, and computer science, and NIH welcomes applications from investigators in these disciplines.

NIH encourages BRAIN Initiative applications from groups that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

The BRAIN Initiative will require a high level of coordination and sharing between investigators, and this FOA will use a cooperative agreement to facilitate these activities. The details of the management of the cooperative agreements can be found in Section VI. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made.

Ultimately, the BRAIN Initiative seeks to understand the circuits and patterns of neural activity that give rise to mental experience and behavior, which will provide a foundation for understanding and treating diverse neurological, psychiatric and behavioral disorders. Dynamic activity of ensembles of neurons in specially organized networks gives rise to the internal states we experience as sensations, perceptions, emotions, thoughts, and memories. The activity of these networks is the substrate of cognitive processes such as attention, intention, reasoning and decision making. Dysfunction of these large systems of neurons due to disease, injury or developmental anomaly is the basis of neural and mental disorders. Further, investigative studies of neural circuits in human subjects offer unique opportunities for mechanistic understanding of complex capabilities especially advanced in humans.

While research using non-invasive imaging and stimulation methods is typically considered non-significant risk by Institutional Review Boards and does not require an Investigational Device Exemption (IDE) from the FDA, opportunities for research involving invasive, higher-resolution stimulating/recording devices for human neuroscience research often have limited time windows. These opportunities are mostly restricted to patients undergoing neurosurgical procedures or implantation for less than 30 days with devices such as ECoG/EEG grids and indwelling penetrating arrays. Among the few stimulating/recording devices that are FDA market-approved for implantation for greater than 30 days are the electrodes for Deep Brain Stimulation (DBS) for Parkinson and Essential Tremor or Obsessive Compulsive Disorder (OCD) and recent stimulating/recording systems for intractable epilepsy. These inherent challenges associated with research using invasive devices in the human nervous system therefore require a greater degree of planning and interdisciplinary collaboration.

Investigations within the human brain offer revolutionary, but challenging, opportunities for experimental investigation of how the brain thinks, perceives, remembers, plans, activates movements and makes decisions. Invasive surgical procedures provide the unique ability to record and stimulate neurons within precisely localized brain structures in humans. However, human studies using invasive technology are often constrained by a limited number of patients and resources available to implement complex experimental protocols and are rarely aggregated in a manner that addresses research questions with appropriate statistical power. Therefore, this FOA seeks applications to assemble integrated, multi-disciplinary teams to develop exploratory and directed research efforts to overcome these fundamental barriers. Projects should investigate high-impact questions in human neuroscience and disorders of the human nervous system. In the case of early-stage exploratory studies, designs should be offered to turn early-stage, range-finding data into mechanistic models and hypotheses, including validation of biological presumptions. More advanced stages of study should propose prospective testing and validation of explicit or model-driven hypotheses. Research designs can be offered as pilot projects, exploratory research or specific research aims, and for building teams and data that will later compete for continued funding under new or ongoing FOAs of the BRAIN Initiative or under NIH Institute and Center appropriations.

Projects should describe the engagement of multidisciplinary teams consisting of clinicians, scientists, device engineers, data/computational scientists, regulatory specialists, and/or ethics specialists. Teams may be assembled within a single institution, but because the limited number of patients at any single research center is typically small, integration of research teams across sites is strongly encouraged.

In the interest of iterative models of discovery, support for complementary animal studies may be allowed if they validate or inform these empirical studies of human physiology or dysfunction. Applicants are expected to employ approaches guided by specified theoretical constructs, and are encouraged to employ quantitative, mechanistic models where appropriate.

We anticipate that implantable devices for most of these applications will rely on existing technology sufficiently advanced for an IRB Non-Significant Risk designation, or an FDA IDE without needing significant additional pre-clinical testing on the device. We also anticipate that newly IDE-approved devices may become available over the course of these awards. NIH BRAIN is supporting new device development and regulatory approval through other NIH BRAIN initiatives, including the availability of template Memoranda of Agreements (MOUs), Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) with various private and commercial device providers that may facilitate awardees to adopt novel technologies to fit their needs (see http://braininitiative.nih.gov/ for up to date information and NIH Scientific/Research contacts). Where appropriate, applicants are encouraged to anticipate potential and alternative plans for adopting newly available technologies. Further, use of the cooperative agreement mechanism will allow awardees to negotiate the incorporation of new technologies by working through NIH Program staff in collaboration with technology providers.

Activities Supported

The list below includes representative, but not exhaustive, examples of activities that could be considered responsive to this FOA.

• Applications may span exploratory and pilot studies, to statistically powered research investigations.
• Applications may integrate non-invasive technologies to image and/or perturb the nervous system to be used in conjunction with the invasive implants to cross spatial and temporal scales.
• Applications may seek to acquire approvals necessary for multi-modal techniques used in combination.
• Applications may offer planning and range-finding empirical designs when they are used to develop testable theories and hypotheses as a launch point for further studies with statistically-powered hypothesis testing.
• Applications may offer the combination of quantitative psychophysics and behavioral assays in combination with brain recording or stimulating that tests mechanistic hypotheses.
• Applications may utilize approved, chronic implants, (e.g., DBS implants; FDA-approved indwelling electrodes) to address mechanistic hypotheses about brain function, plasticity, disease progression, etc.

Topics supported

The list below includes representative, but not exhaustive, examples of topics that could be considered responsive to this FOA.

• Approaches to understanding network coding of sensory information.
• Paradigms to assess motor coding during complex behaviors.
• Approaches to understand neural circuitry associated with diverse social behaviors.
• Changes in circuit functions underlying the brain's ability to store information and to learn new behaviors (plasticity).
• New approaches to capture and assess information processing across brain regions during memory consolidation, memory retrieval, spatial/relational processing, attention, or planning.
• Assessment of distributed representations and information processing underlying advanced mental processes such as decision making, numerical cognition, reasoning, and metacognition.
• Investigation of distributed circuits that contribute to the coordination of motivational states and reward behavior.
• Empirical and analytical approaches to understand how behavioral states are emergent properties of the interaction of neurons, circuits, and networks.
• Investigative studies of the circuit basis of neurological, psychiatric, communication and behavioral disorders and dysfunctions in humans.
• Studies of disease biology critical in the context of informing optimized neuromodulation therapy.

The following are non-responsive for this program:

• Studies for which the primary goal is to achieve regulatory approval of neurotechnology (see http://braininitiative.nih.gov/ for other BRAIN FOAs supporting this activity, and the NIH bioengineering grant program http://www.ninds.nih.gov/research/bioengineering/index.htm ) or the peripheral nervous system (see NIH SPARC http://commonfund.nih.gov/sparc/index )
• Imaging approaches not coupled with intra-cranial recording or stimulating
• Implementing rehabilitation therapies
• Definitive clinical trials of therapeutic devices, such as a traditional feasibility study and/or pivotal trial (see http://www.fda.gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103.pdf2 for the definition of an early feasibility study, feasibility study and pivotal trial)
• Projects focused on augmentation of neural function in healthy individuals

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

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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:

James Gnadt, PhD
6001 Executive Blvd
North Bethesda, MD 20892
NSC 2230
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.

Other Attachments: Applicants are required to include the following items: Team Management Plan and Clinical Protocol Synopsis. These items must be uploaded as separate attachments in pdf format with filenames that correspond to the individual items (Team Management Plan, and Clinical Protocol Synopsis). Applications lacking these required items will be deemed incomplete and will not be reviewed.

Team Management Plan: The team management plan must not exceed one page; applications that exceed this limit will be withdrawn. NIH strongly encourages applicants to form multidisciplinary teams that consist of clinicians, scientists, device engineers, mathematicians, statisticians, data scientists, regulatory specialists and/or ethics specialists, as appropriate. This multidisciplinary team should be able to address the details of the plans and experiments, and to execute the research strategy. An organizational structure that clearly defines the team structure and relationships among the various components must be described in the team management plan and illustrated in an organizational chart. This plan should also describe the governance and organizational structure of the leadership team and the research project, including communication plans, processes for making decisions on scientific direction, and procedures for resolving conflicts. For publications, policies to address the ordering and recognition of authors, and decisions about what material to publish, consistent with the interests of commercial partners (where applicable), should be presented.

The team management plan should establish a Scientific Steering Group that consists of representatives from each of the partnering organizations and meets regularly to discuss project status, problems, and directions. Those individuals identified in the team management plan, who together would have the intellectual and leadership responsibilities, would likely be members of the Scientific Steering Group. Plans for enhancing the abilities and opportunities for investigators to work across disciplinary boundaries should also be included.

Clinical Protocol Synopsis: The clinical protocol synopsis must not exceed six pages; applications that exceed this limit will be withdrawn. The clinical protocol synopsis must include the following information:

• Compliance with HIPAA and informed consent must be explicitly described.
• A list of participant eligibility criteria
• Applications should specify how recruitment and retention plans will accommodate access to the appropriate brain areas of recording, including a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants, including women and minority participants.
• Participant recruitment and retention plans, including a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants meeting the eligibility criteria, including women and minority participants. Data supporting recruitment and retention estimates must be provided.
• A description of all assessments including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions.
• Discussion of the potential biases in the study and how they will be addressed
• Statistical Methods: Discussion of sample size and power calculations where hypothesis testing is explicit, study outcome measures, plans for interim and final analyses, methods of bias control, and methods for handling missing data. Examples of the critical elements of a well-designed clinical study are summarized on the NINDS website. http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf.
• Data Management and Quality Control: Details of efficient data management and methods for monitoring quality, methods for monitoring the quality and consistency of intervention administration, and methods for ensuring participant confidentiality. Applicants are expected to incorporate data elements from the NINDS Common Data Elements (CDE) Project in their data collection forms (see http://www.commondataelements.ninds.nih.gov )
• Discussion of the challenges expected in implementing the trial and how these might be overcome
• Data and Safety Monitoring Plan: Applicants must include a Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical study (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html). For exploratory clinical studies it generally will be acceptable for the data and safety monitoring to be conducted by an investigator-appointed Study Monitoring Committee (SMC), an Independent Medical Monitor (IMM), or, for single-site trials involving low risk, the Program Director/Principal Investigator and his/her IRB. However, NIH may decide to establish an independent Data and Safety Monitoring Board (DSMB) depending on the score and risk of the trial. Applicants should refer to NIH’s policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html) as well as the NINDS Guidelines for Data and Safety Monitoring (http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm

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

Applications to this FOA should assemble integrated, multi-disciplinary teams of clinicians, scientists, device engineers, mathematicians, statisticians, data scientists, regulatory specialists and/or ethics specialists, as appropriate, to propose innovative research plans within the context of the unique research opportunities offered by these clinical procedures. These teams may be assembled within a single university or medical center, or may comprise integrated teams across multiple institutions to aggregate these limited opportunities to address high-impact neuroscience questions.

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, with the following additional instructions:

Research Strategy: Harmonization of recruitment, methods and data sharing (including collection, curation, analysis and sharing) across multiple sites should be well planned and described as appropriate and consistent with achieving the goals of the program. Projects should be offered as pilot or exploratory research activities that will build teams and data that will later compete for continued funding under new or ongoing FOAs of the BRAIN initiative or under NIH Institute and Center appropriations.

All applications are required to include the following points, which must be incorporated within the page limits of the Research Strategy:

• Statement of the neurobiological, neurological or mental health questions to be addressed, including the theoretical and conceptual framework that drives the research design and questions, and discussion of the analytical methods for interpreting the results.
• Description of how studies in the brain tissues potentially affected by the disease or disorder can adequately address the research questions and mechanisms posed, including comparison to complementary studies in animals if appropriate and feasible.
• Description of recording/manipulation methods that will be employed or developed to approach the questions as a functional system, and how the invasive intervention and/or the implantation of foreign (device) materials may confound the interpretation of results.
• If complementary animal studies are proposed, then anticipated or contingent, non-human, experimental components must be adequately described and justified
• Where the adoption of newly developing technology pending FDA-approved is anticipated, reasonable description as an alternative methodology (to the extent that details are available), along with potential advantages and pitfalls, is required.
• Description of a timeline for completion of tractable research goals, strategic goals and key stages of progress for the project, especially in terms of participant accrual.
• Where explicit hypothesis testing is proposed, the application must include a statistical power calculation for the planned studies, per patient and/or as repeated measures within patients.
• Applicants must address the technical, procedural and ethical aspects specific to invasive studies in human patients, and the strategic plans for addressing functional studies of a specified neural system in the context of patients with neural dysfunctions and invasive device interventions.
• Projects are allowed to include early-stage research and planning efforts. Thus, preliminary data on feasibility are allowed but not required. However, a sound rationale should be offered as to why the approach and the research team are the most appropriate, and likely to generate exceptionally high impact if successful.

Protection of Human Subjects:

Assurance of the protection of human participants and the biohazard safety of employees (if applicable) must be provided for the overall study and for each clinical site. The applicant must discuss any issues which might lead to concern for the welfare of participants. Additionally, the human subjects section of the application must address data security measures and confidentiality.

Long-Term Plan for Patients: Applicants must describe a plan for the care of patients at the end of the study and after the study period, if appropriate. These plans may vary from project to project, but examples might include 1) explant of indwelling devices once the approved study period is complete, 2) surgical removal of batteries and capping the exposed metals from leads/IS-1 connectors, 3), manufacturer-supported device maintenance for patients responding to therapy, 4) manufacturer support for filing of compassionate use exemptions for device maintenance, etc.

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, including description of plans for accommodating research-community input and requests for collecting and disseminating data that will be valuable to the wider research community beyond the primary outcomes. IRB-compliant plans for sharing de-identified data for maximizing and expanding dissemination of data collected from this precious resource should be included in the research plan, including statements of cooperation to join a future collaborative consortium of awardees to maximize the data sharing (including collection, curation, analysis and sharing) for this unique population of human subjects.

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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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 NINDS Scientific Review Branch and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Consultation with relevant Scientific/Research staff at least 10 weeks prior to the application due date is strongly encouraged. This is not the same as the Letter of Intent and should be included as a separate communication to the Scientific/Research Contacts, see Section VII. If requested by the applicants, program staff can advise whether the proposed project meets the goals of this FOA and the mission of the BRAIN initiative, and discuss responsiveness questions. Program staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. During the consultation phase, if the proposed project does not meet the programmatic needs of this FOA, applicants will be strongly encouraged to consider other FOAs.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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:

In addition to the review criteria below, reviewers will assess the technical, procedural and ethical aspects specific to invasive studies in human patients, and the strategic plans for addressing functional studies of a specified neural system in the context of patients with neural dysfunctions and invasive device interventions.

Because projects are expected to include early-stage research and planning efforts, preliminary data on feasibility are not required, and should be considered within the context of the specific stage of proposed studies. Reviewers will consider feasibility, but will not penalize well-reasoned justifications of new and innovative approaches. However, a sound rationale should be provided as to why the approach and the research team are the most appropriate, and likely to generate an exceptionally high impact if successful.

In the interest of the possibility of adopting new and developing technologies during the award, when applicants offer anticipated or alternative, newly developed, IDE-approved devices in the research plan, reviewers should assess feasibility, risk and opportunity, along with strategic contingencies.

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? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

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

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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.

Plans for Patient Recruitment/Retention

Does the application document the following?

• Availability of the requisite eligible subject pool in proposed clinical center(s);
• The status of evidence showing whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected (see Inclusion of Women and Minorities in Clinical Research below);
• Are the sites and plans presented appropriate for the inclusion of minorities and women?
• Plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals; and
• Are retention plans and practices adequate?

For research that involves human subjects but does not involve one of the six 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 six 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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• 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 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.

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the U01 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:

The PD(s)/PI(s) will have primary responsibility for defining objectives and approaches, and for planning, conducting, analyzing, interpreting, drawing conclusions on their studies, publishing and sharing the results.

Awardees will retain custody of and have all rights to the data and technology developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

Awardees are responsible for pursuing patent protection.

Awardees are responsible for providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether research goals have been met or not. In cases when NIH program staff request raw data, awardees agree to provide the data.

Awardees agree to participate at least once a year in progress meetings (teleconferences) that are organized by NIH staff.

Regarding meetings and interactions with regulatory agencies, awardees agree to communicate meeting dates and agenda to the NIH program staff and invite their participation.

Awardees agree to communicate study reports from CROs, meeting minutes (and associated data packages if applicable), letters and other forms of communications with FDA, Recombinant DNA Advisory Committee (RAC), and other authorities, and to provide IND# and registration numbers in clinical trial.gov, if applicable.

Awardees are responsible for providing regulatory and clinical documents that are required for administrative review.

Awardees must verify that the clinical trial is performed in accord with Good Clinical Practices (GCP) and in accord with NINDS Guidelines for Data and Safety Monitoring in Clinical Trials: http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm, and must provide data and regular updates to NIH.

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

Each project will have the support of one or more Project Scientists from NIH program staff who are assigned an administrative role for the nervous system disorders being studied and have expertise in the implementation of translational research.

The NIH Project Scientists will have substantial scientific/programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.

NIH Project Scientist(s) provides input on the research goals and makes decisions regarding their finalization.

NIH Project Scientist(s) will be responsible for assessing the progress of the project towards the specified research goals, and for recommending if further funds should be released to the project.

NIH Project Scientist(s), in consultation with the PIs, may add critical experiments that need to be conducted prior to or during the award as an additional research goals. In most cases, these studies will be supported by additional funds from NIH.

NIH Project Scientist(s) participates in meetings together with PIs with regulatory agencies related to the funded project.

An important part of the program is the coordination of research efforts across different funding mechanisms and research capabilities, and the coordination among efforts aimed at different nervous system disorders. NIH Project Scientists will have the primary responsibility for this overall coordination.

Additionally, an agency Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned Program Officer may also serve as an NIH Project Scientist.

NIH leadership will make decisions on project continuation based on program staff recommendations, programmatic prioritizations and budget considerations. NIH program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year research goals may be revised based on data and information obtained during the previous year. If, based on the progress report, a funded project does not meet the defined research goals, funding for the project may be restricted or discontinued.

In addition to research goals, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the specific aims), overall progress, NIH portfolio balance and program priorities, competitive landscape, and availability of funds.

Areas of Joint Responsibility include:

Clarifying and negotiating the research goals and timelines

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 for the investigators 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 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. Final decisions made by NIH regarding a discontinuation are not appealable.

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.

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

eRA Commons Help Desk (Questions regarding 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 CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

James Gnadt, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]

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

Tijuanna E. DeCoster, Ph.D.
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.