All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.
Reissue of RFA-NS-18-029
March 2, 2022 - This Announcement has been reissued as RFA-NS-22-028
April 28, 2020 - Notice of Correction to Key Dates for RFA-NS-20-029. See Notice NOT-NS-20-063
July 26, 2019- Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128
August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
93.853, 93.273, 93.866, 93.213, 93.279, 93.173, 93.286, 93.867, 93.865, 93.242, 93.313
This funding opportunity announcement (FOA) is designed to support teams of investigators that seek to cross boundaries of interdisciplinary collaboration to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications are encouraged to propose adventurous and challenging goals that can only be tackled by a synergistic team-based approach and have the potential to be transformative and/or to enable significant advances. These studies at the exploratory stage are intended for the development of experimental capabilities and/or theoretical frameworks in preparation for a future competition for larger-scale or extended efforts, including the BRAIN TargetedBCP R01 or the multi-component, Team-Research BRAIN Circuit Programs (U19).
The overall goal of this FOA is to enable a large-scale analysis of neural systems and circuits within the context and during the simultaneous measurement of an ethologically relevant behavior. Toward this end, teams are expected to assemble and leverage multi-disciplinary expertise, and to integrate experimental with computational and theoretical approaches. Teams are expected to bridge fields by incorporating rich information on cell-types, on circuit functionality and connectivity, in conjunction with sophisticated analyses of an ethologically relevant behavior of an organism or a well-defined neural system. Teams are also expected to aim for a mechanistic understanding of the circuits of the central nervous system (CNS) by applying cutting-edge methods such as those for large-scale recording, manipulation, and analysis of neural circuits across multiple regions of the CNS.
April 1, 2020
June 14, 2020
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
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.
The BRAIN Initiative
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is 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, will show 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 even 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 Funding Opportunity Announcement (FOA) and other FOAs issued in Fiscal Year 2020 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. Videocasts of the NIH BRAIN Multi-council Working Group are available at http://www.braininitiative.nih.gov/about/mcwg.htm..
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 support those research efforts through investigator-initiated applications as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact Scientific/Program staff if they have any questions about the best FOA for their research.
To enable rapid 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 and information sciences; and NIH welcomes applications from investigators in these disciplines.
As noted in NOT-OD-20-031,NIH encourages BRAIN Initiative applications from investigators 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.
This FOA is related to the Recommendations in Section III. 2, 3, 4, 5 and 7 of the Final Report (http://www.nih.gov/science/brain/2025/index.htm) of the BRAIN working group. Specifically, this FOA solicits applications that will address the recommendations on “Maps at Multiple Scales”, "The Brain in Action", "Demonstrating Causality", "Identifying Fundamental Principles" and “From BRAIN Initiative to the Brain” (Section III Implementation: Goals, Deliverables, Timelines and Costs, Parts 2 3, 4, 5 and 7) of the Final Report.
Background of this FOA
The broad goal of the BRAIN Initiative is 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. It is the dynamic activity of massively interconnected ensembles of neurons in specially organized networks that give rise to the internal states we experience as sensations, perceptions, emotions, thoughts, memories, and movements. The activity of these networks is the substrate of cognitive processes such as attention, intention, emotions, and rational processes such as reasoning and decision making. Ultimately, these covert, internal activities are translated into patterns of neural activation that lead to overt behaviors, from simple reflexes to highly coordinated movements such as reaching and walking, to more complex behaviors such as navigating the environment and foraging, or speech and language. Dysfunction of these large systems of neurons due to disease, injury or developmental anomaly is the basis of neural and mental disorders.
We can seek to understand circuits of the CNS by systematically controlling stimuli and measuring the resulting behaviors, while actively recording and manipulating the dynamic patterns of neural activity. We now have transformational technologies that allow us to record large, interrelated ensembles of neurons on an unprecedented scale during active behaviors. For example, it is now possible to study the collective neural activities of entire sensory-motor circuits. By clever manipulation of environments and contingencies, we can devise behavioral tasks that engage memories, decision making, and selective attention, while documenting and manipulating the functional relationships within the neural circuits that subtend the behaviors.
Increasingly, sophisticated approaches are required for data acquisition, analysis, interpretation, and dissemination. These demanding requirements often involve expertise not typically associated with traditional neurobiological experiments and training, such as expertise in physics, computer and information science, hardware and software engineering, statistics, machine learning, and computational methods. As new, large-scale, systems approaches become routine, it will be essential to develop testable theories of how information originating from millions of neurons in diverse and widespread CNS regions can be integrated to produce a wide range of internal, motor, sensory, and cognitive behaviors, and how this information evolves dynamically to adapt, refine, and learn.
Towards the goal of understanding the circuit basis of behavior, we offer a family of Integrated Approaches NIH BRAIN FOAs that share an overall goal of understanding the circuit basis of behavior. These FOAs range from small or exploratory (Targeted BCPP R34) vs targeted brain circuits projects with specific research deliverables (Targeted BCP R01) to large, team-research projects with exploratory aims (eTeamBCP U01, this FOA) or with extensive and elaborated goals and a 5-10 year horizon of discovery (Team BCP U19). This set of funding opportunities is designed to allow for the tackling of scientific questions at different scales and of various complexities, and to balance support for individual-lab science and team-science approaches. In each case, the FOAs are guided by BRAIN 2025 A Scientific Vision: “The Application of Integrated Technologies to Study Fundamental Questions in Neuroscience: Numerous long-standing problems in CNS science will benefit dramatically from the integrated experimental approach made possible by the BRAIN Initiative.” Potential applicants are encouraged to visit the NIH BRAIN Initiative website for information and guidance https://www.braininitiative.nih.gov/funding/initiatives.htm.
Purpose of this FOA
Per the BRAIN 2025 report, "No single researcher or discovery will solve the brain’s mysteries. The most exciting approaches will bridge fields, linking experiment to theory, biology to engineering, tool development to experimental application, human neuroscience to non-human models, and more, in innovative ways.” Hence, the purpose of this exploratory FOA is to provide resources for the integration of experimental, computational, and theoretical capabilities for the large-scale analysis of neural systems and circuits within the context and during the simultaneous measurement of behavior.
This exploratory FOA will support the building of teams of experts that seek to cross boundaries of interdisciplinary collaboration by bridging fields and by linking theory, modeling, and/or data analysis to experimental design. Teams are expected to develop or adopt a conceptual or quantitative modeling framework, which incorporates theories about causal mechanisms of circuit functions, to drive experiments and build testable hypotheses. Innovative and mechanistic approaches to cross-cutting questions in neuroscience are expected; this FOA emphasizes the use of cutting-edge methods of activation, recording, and/or analysis to understand the behavior of circuits at cellular and sub-second levels of spatial and temporal resolution, that is, at the level of the functional units of circuits. Diverse species or experimental systems and a cross-species/comparative approach are welcome and should be chosen based on their power to address the specific question at hand and to reveal generalizable and fundamental principles.
Proposed exploratory studies should lead to subsequent, competing applications for support of team-research projects (e.g. Targeted BCP R01, TeamBCP U19) consistent with the BRAIN Initiative's goal to understand the circuits of the CNS, to measure the fluctuating patterns of electrical and chemical activity flowing within those circuits, and to understand how their interplay creates our advanced cognitive and behavioral capabilities.
The list below includes representative, but not exhaustive, examples of topics that could be considered responsive to this FOA. We welcome projects that employ mechanistic, cutting-edge, integrated, and innovative approaches to:
This FOA welcomes basic research using human or non-human animal subjects; applications for the study of specific disease mechanisms, or specific disease therapeutics, interventions, and treatments will be considered non-responsive to this BRAIN Initiative FOA and will be withdrawn. Studies for the investigation of specific diseases and disorders should be directed to the appropriate NIH Institutes.
If proposing a clinical trial, this FOA will only accept basic experimental studies in which participants are prospectively assigned to experimental conditions and receive an intervention or experimental manipulation where the effect will be assessed for the purpose of understanding fundamental aspects of phenomena. Human studies with invasive (intra-cortical) recording and/or stimulating must include neuroethical considerations, such as consent of patients recruited into studies with possibility for risk beyond therapeutic standards of care without expectation of personal therapeutic benefit. Additional risks should be identified and justified as minor and manageable. Consent methodology should avoid patient coercion or therapeutic misconception.
Prior Consultation with IC staff
Applicants are strongly encouraged to consult the Scientific/Research Contact listed below to discuss the alignment of their proposed work with the goals of this FOA and the BRAIN Initiative Program.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NIH BRAIN Initiative intends to commit $12M in FY2020 to fund around 5 awards.
The project period must be three years.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not 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 must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Applications submitted in response to this solicitation may not duplicate or be substantially similar to other applications concurrently under consideration by other programs or study sections including the inter-agency programs such as Collaborative Research in Computational Neuroscience (CRCNS), EArly-concept Grants for Exploratory Research (EAGER) or Next Generation Networks For Neuroscience (NeuroNex). Duplicate or substantially similar applications will be withdrawn.
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Dr. Karen K David
6001 Executive Blvd
North Bethesda, MD
All instructions in the SF424 (R&R) Application Guide must be followed.
Research Strategy: This FOA supports exploratory collaborative studies to develop experimental capabilities and theoretical frameworks to prepare for a future team-science effort, focused on understanding a specific behavioral or neural system in terms of circuit dynamics.
All applications should include the following points, which should be incorporated within the page limits of the Research Strategy:
Other specific requirements and considerations:
Applications must apply NIH standards of experimental and publication rigor (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-011.html), should strive to promote ethnic, racial, gender and career stage diversity of the research teams, and must comply with NIH policy on reporting disaggregated sex-based data and other consideration of sex as a biological variable as elaborated in NOT-OD-15-102, NOT-OD-15-103 and NOT-OD-16-031.
The following modifications also apply:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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.
Applications Involving the NIH Intramural Research ProgramThe requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.
Prior Consultation with Scientific/Research StaffConsultation with relevant Scientific/Research staff is strongly encouraged, not later than the Letter of Intent due date. 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, staff can advise whether the proposed project meets the goals of this FOA and the mission of the BRAIN initiative, and discuss responsiveness questions. 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 Funding Opportunities.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
This FOA supports exploratory collaborative studies to develop experimental capabilities and/or theoretical frameworks to prepare for a future larger-scale or extended research effort, focused on understanding a specific behavioral or neural system in terms of circuit dynamics.
Because projects are expected to be early-stage and potentially high-risk, preliminary data are not required. However, a sound rationale should be provided as to why the approach is tractable, the research team are the most appropriate, and the project likely to generate an exceptionally high impact if successful. Although reviewers will be asked to consider feasibility, they will be instructed to not penalize unavoidable risks that are intrinsic to new and innovative approaches.
In addition, for applications involving clinical trials:
A proposed clinical trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or leads to new avenues of scientific investigation.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
In addition, for applications involving clinical trials:
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Specific to this announcement:
Does the project seek to identify fundamental principles or produce conceptual foundations about circuit dynamics and functional connectivity ? Does the project justify how its development of experimental capabilities and/or theoretical frameworks will prepare for a future competition for larger-scale or extended team-research awards?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
In addition, for applications involving clinical trials:
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Specific to this announcement:
Reviewers should assess whether the multiple approaches and collaborations offer a team-research synergy that would not be possible as separately funded individual research project award mechanisms. Reviewers should assess whether the team seek to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to experimental design.
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?
In addition, for applications involving clinical trials:
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Specific to this announcement:
Does the project offer potentially transformative and paradigm-shifting advances in understanding brain circuitry underlying behavioral or neural systems? Innovative approaches to cross-cutting questions in neuroscience are expected.
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
In addition, for applications involving clinical trials:
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this announcement:
Reviewers should assess the methods, justification, or integration plans, as follows:
Does the project use cutting-edge methods of activation and recording to understand behavior or a neural system in terms of a mechanistic understanding of specific circuits at cellular and sub-second levels of spatial and temporal resolution? Is the scale of recording sufficient to account for the dynamic activity of the circuit or distributed ensemble of neurons under study, or to validate a specific, model-predicted outcome? This should be evaluated using species-appropriate considerations.
Does the project justify how the selected species offer the best conditions for revealing general principles about the circuit basis of the specific behavior or neural system of interest?
Does this project seek to bridge fields, integrating experimental, computational, and/or theoretical capabilities? Is there a theoretical framework (conceptual or quantitative) for building testable hypotheses?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
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?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure.
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
For studies involving invasive (intra-cortical) recordings in humans:
Does the application adequately address neuroethical considerations about informed consenting of research subjects who can expect no direct benefit from engaging in the investigative research proposed, considerations of FDA-defined conditions of non-significant risk/significant risk beyond established standards of clinical care, ethical and practical considerations of invasive device maintenance and explantation, and other ethical issues specific to invasive human neuroscience research?
Reviewers should assess the plan for the care of patients at the end of the study and after the study period.
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).
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 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.
Information regarding the disposition of applications is available 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.
Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
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 75and 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:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
None; all responsibilities are divided between awardees and NIH staff as described above.
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.
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 agreementsare 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.
Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Karen K David, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
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