National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
The purpose of this Notice of Funding Opportunity (NOFO) is to encourage grant applications for investigator-initiated prospective observational comparative effectiveness research (CER) to the National Institute of Neurological Disorders and Stroke (NINDS) (note: only prospective observational studies will be considered). The study must address questions within the mission and research interests of the NINDS and may evaluate preventive strategies, diagnostic approaches, or interventions including drugs, biologics, and devices, or surgical, behavioral, and rehabilitation therapies. NINDS is particularly interested in pragmatic study designs that utilize a cost-effective means of prospectively collecting observational data important to current clinical practice.
30 days prior to application due date.
Application Due Dates | Review and Award Cycles | ||||
---|---|---|---|---|---|
New | Renewal / Resubmission / Revision (as allowed) | AIDS - New/Renewal/Resubmission/Revision, as allowed | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
February 19, 2025 | March 18, 2025 | May 07, 2025 * | July 2025 | October 2025 | December 2025 |
June 18, 2025 | July 18, 2025 | September 07, 2025 * | November 2025 | January 2026 | April 2026 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the NOFO) 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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
Background
The gold standard of evidence for establishing the utility and success of therapeutic interventions is the randomized clinical trial (RCT). However, challenges in the design and execution of definitive RCTs and obstacles to implementation of trial results often limit their use in specific settings. One example of an obstacle is the ideal context in which the trial is conducted (efficacy), rather than a real world setting (effectiveness) where the intervention would be implemented eventually. Even a well-designed efficacy RCT may be difficult to interpret because of exceptions from randomization, such as dropouts, cross-overs, or missing data. Given the high cost of traditional RCTs and their potential limitations, other approaches to developing rigorous evidence to support clinical decision-making are needed. One example of this approach is the prospective observational comparative effectiveness study design.
The purpose of this Notice of Funding Opportunity(NOFO) is to encourage grant applications for investigator-initiated prospective observational comparative effectiveness studies. For the purposes of this NOFO, comparative effectiveness research (CER) is defined as the conduct of research comparing the benefits and harms of different existing interventions and strategies to prevent, diagnose, treat and monitor health conditions in real world settings (modified from Federal Coordinating Council for Comparative Effectiveness Research. Report to the President and the Congress. US Department of Health and Human Services, 2009; https://osp.od.nih.gov/wp-content/uploads/FCCCER-Report-to-the-President-and-Congress-2009.pdf) . The NINDS has a longstanding interest in CER. CER typically utilizes real world settings to compare existing interventions or strategies that have been studied individually in randomized controlled trials (RCT), that are commonly used clinically despite the absence of evidence from prior controlled trials, or that are used in settings where patients might have treatment preferences, despite equipoise among medical care providers. A comparative effectiveness approach may also be useful to:
Broadly speaking, CER can be performed using a variety of methods, including prospective observational studies, clinical trials, or structured evaluation of existing evidence from registries, electronic health records, and other databases (e.g., meta-analyses, systematic reviews, modeling). An important component of CER is the application of analytical strategies, such as multivariable regression, propensity score analysis, and instrumental variable analysis, to adjust for known inherent biases resulting from lack of randomization.
For this NOFOonly prospective observational studies will be considered for funding. Other types of CER studies may be submitted to other NOFOs, if applicable. The grant mechanism used to support this funding announcement is a cooperative agreement (UG3/UH3) mechanism with two phases. The initial milestone-driven planning phase (UG3) will last for up to 2 years, with possible transition to a prospective observational study phase of up to 5 additional years (UH3). Only UG3 projects that have met scientific milestones and feasibility requirements will be approved to transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application. The UG3 phase for observational studies will permit both scientific and operational planning activities. The UH3 phase of the award will support the conduct of investigator-initiated prospective observational studies.
The UG3 award (Planning Phase) will provide up to 2 years of support for scientific and operational planning activities required (not yet completed) to prepare for conduct of a subsequent CER study. The UH3 award (Implementation Phase) will provide up to 5 years of support for conduct of the CER study in accordance with activities planned in the UG3 phase. This study should have an overall hypothesis, be milestone-defined, and have the potential for high impact within the research mission of NINDS. The study must meet all applicable NIH and Office of Human Research Protections (OHRP) policy requirements.
UG3/UH3 Transition: At the completion of the UG3 planning phase, the applicant will be required to submit an RPPR that includes the list of completed milestones (developed in collaboration with the PI as part of the initial Notice of Award) to progress to the UH3 implementation phase. These UH3 transition requests will undergo administrative review by NIH staff to determine whether the study will be awarded the implementation phase (UH3). Transition decisions will be based on achievement of study milestones, readiness to conduct the UH3 study, feasibility of completing the UH3 study, availability of funds, and program priorities.
Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 implementation phase. UH3 funding is dependent on NINDS program priorities and availability of funds. In addition, applicants should understand that transition to the UH3 phase of the project will occur only if the administrative review process determines that the UG3 planning milestones have been successfully met and that the UH3 phase can proceed with confidence of success.
Additional Information
Each NINDS UG3/UH3 Cooperative Agreement application may only be used to propose the planning and implementation of a single prospective observational study.
Studies of outcomes in populations that typically are subject to health disparities and under-representation in clinical trials (including, but not limited to, racial and ethnic minorities, persons with disabilities, children, the elderly, and patients with multiple chronic conditions) are particularly encouraged (https://www.healthypeople.gov/2020/about/foundation-health-measures/Disparities).
Diseases, disorders, and conditions that are considered to be under-researched (particularly with respect to burden of illness) are also encouraged.
Applicants should take note of the following special requirements and considerations:
Limited studies of outcomes that are not included in typical care may be included (e.g., limited implementation of neuropsychological studies) as part of a fully-powered secondary hypothesis.
3. Relationships with Patient Groups: Applicants are strongly encouraged to establish relationships with patient groups and solicit their input on recruitment, the clinical meaningfulness of the question under study, the relevance of the proposed clinical outcomes, and approaches to minimizing the burden on study subjects. There is particular interest in
underrepresented and underserved populations patient and community groups.
4. IRB documentation: IRB approval of the protocol and informed consent are not required at the time of application submission unless the UG3 phase involves human subjects; it is required prior to UH3 (Implementation Phase) funding. Applications must comply with the Federal sIRB mandate (45 CFR 46.114) and the NIH Single IRB Policy for multi-site research, if applicable (https://grants.nih.gov/policy/clinical-trials/single-irb-policy-multi-site-research.htm) . NINDS encourages investigators to begin these processes as early as possible. NINDS also will require documentation of any other necessary regulatory approvals (e.g., Recombinant DNA Advisory Committee) prior to funding, if applicable.
5. NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including:
6. Innovative Technologies: Applicants are encouraged to consider utilizing (at least experimentally) digital/mobile/sensor technologies and web-based systems to facilitate data collection (including data collection in a continual, contextual, real-world setting) and to enhance protocol adherence. Innovative statistical approaches are also encouraged, when appropriate.
7. Consultation with NINDS: Applicants are strongly encouraged to consult with NINDS Scientific/Research staff well before an application is developed (see Section VII, Agency Contacts).This early contact will provide an opportunity to clarify NINDS policies and guidelines as well as to discuss how to develop an appropriate project timeline and milestone plan, which is subject to peer review. The NINDS considers program priorities and scientific overlap with other funded projects. Scientific/Research contacts are also available to discuss strategies for recruitment and inclusion of women and minorities.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.
The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Not Allowed: Only accepting applications that do not propose clinical trials.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Up to 2 years for the UG3; up to 5 years for the UH3.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.
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 their organization to develop an application for 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 How to Apply-Application Guide.
This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.
Number of Applications
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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.
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:
Adam L. Hartman, MD
Telephone: 301-496-9135
E-mail: [email protected]
All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.
All instructions in the How to Apply - Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply-Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:
Significance: There should be a justification of why an RCT cannot be performed to answer the main experimental question(s) posed in the application. As the nature of CER is a comparison of treatments, there should be a justification for selection of the proposed interventions from amongst the many available options. The goal is to target effectiveness (i.e., "real-world" environment with few inclusion/exclusion criteria) rather than efficacy (i.e., ideal conditions with limited numbers of patients with strict inclusion/exclusion criteria), so the proposed study should have the potential to inform decisions by key stakeholders, including patients, clinicians, and/or policymakers. Study outcomes should target the intended population for the intervention because of the "real world" nature of the investigation. Similarly, the application should address priorities articulated by patients, clinicians, and/or policymakers and the priorities of these groups should be gauged prior to submission and reported in the application. The application should address an area of need, such as an underserved population or disease entity.
Investigator(s): The investigator team should be qualified in terms of experimental design, study execution, data handling, and statistical analyses/interpretation of CER-derived data. For a multicenter study, the organizational structure should be appropriate and the application should identify a core of potential center investigators and staffing for a clinical and data coordination.
UG3 Approach: The application should include descriptions of the following:
UH3 Approach: The application should discuss the following:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.
All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan as part of the Resource Sharing Plan (budgets also must include expenses associated with data sharing).
Data Submission and Sharing Policies for the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data from Traumatic Brain Injury clinical research studies must be submitted if they meet the following criteria: (1) TBI-related clinical trials; (2) all unsolicited clinical TBI research grants with a budget greater than or equal to $500,000/year in direct costs; (3) ancillary studies, regardless of budget, to either TBI-related clinical trials or clinical TBI research grants with budgets greater than or equal to $500,000/year in direct costs; and (4) clinical TBI research grants awarded under notices of funding opportunities (NOFOs) with specific requirements for FITBIR data submission. In addition, any TBI genomic studies that generate large-scale genomic data, regardless of the size of the budget, or NIH grant funding mechanism, should follow the guidance of the NIH GDS Policy on data sharing. For more information read the Notice of Modification of the Data Submission and Sharing Policies for the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System https://grants.nih.gov/grants/guide/notice-files/NOT-NS-17-029.html
Autism research involving human subjects funded by NINDS are required to deposit all raw and analyzed data (including, but not limited to, clinical, genomic, imaging, and phenotypic data) into the NDA infrastructure (https://grants.nih.gov/grants/guide/notice-files/NOT-MH-20-010.html).
Other Plan(s):
All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:
Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the How to Apply- Application Guide must be followed.
Section 2 - Study Population Characteristics
2.5 Recruitment and Retention Plan
Applicants must include a discussion of the ability of sites to recruit and retain the proposed number of participants, including women, underrepresented minorities, and individuals across the lifespan. Evidence should be provided that relevant stakeholders (e.g., potential participants, referring and treating physicians, diverse patient groups) have equipoise, view the question to be important and consider the study acceptable.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.
See Part 2. 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. 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, NIHs 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.
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 How to Apply-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 Section 7.9.1 Selected Items of Cost.
Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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 NOFO for information on registration requirements.
The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organizations profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.
Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].
Applicants are required to follow the instructions for post-submission materials, as described in the policy
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.
Reviewers will evaluate Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate criterion score.
Significance
Innovation
Specific to this NOFO:
Assess whether the application addresses an area of need, such as an underserved population or disease entity. Because the goal is to target effectiveness (rather than efficacy), assess whether the proposed study has the potential to inform decisions by key stakeholders, including patients, clinicians, and/or policymakers. Evaluate whether the study outcomes target the intended population for the intervention. Assess the application's responsiveness to priorities articulated by patients, clinicians, and/or policymakers. Evaluate whether these groups' priorities were gauged prior to submission. As interventions proposed for study in this CER NOFO already have been used in practice or already studied in efficacy trials, evaluate the use of existing data that serve as the background/rationale for the study. Assess whether the analysis plan and statistical approach are innovative.
Approach
Rigor:
Feasibility:
Specific to this NOFO:
Assess whether this study be done as a RCT. Evaluate the justification for a CER (rather than an RCT). As a CER study, assess the justification for selection of the proposed interventions (from amongst the many available options). Assess whether the proposed patient cohort is appropriate for the study question at hand. Evaluate the statistical analysis plan, and if applicable, assess the decision rule that will allow a clinically-relevant and focused recommendation at the end of the study. If applicable, assess whether the decision rule accounts for efficacy and safety, thus addressing the optimal benefit vs. risk. Assess whether the application describe data quality and quality assurance, how missing data will be handled, and acceptable attrition rates. If using a noninferiority design, evaluate the noninferiority margin and the justification for that margin. Evaluate whether implications of study results are assessed critically in terms of the statistical limits (i.e., probability distribution) of the data. If proposing multisite recruitment or using recruitment from different sources (e.g., different cohorts), evaluate whether the application describe how these populations differ. Evaluate how well potential confounders considered (i.e., appropriate analyses proposed to account for potential confounders, including a propensity analysis, risk-adjusted regression, or instrumental variable analysis, etc.). If applicable, assess how the application proposes to use NINDS common data elements, and the plan to allow harmonization of outcomes with similar existing or future projects.
Assess whether potential challenges and corresponding solutions are sufficiently discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls). Evaluate whether the UG3 and UH3 milestones specific, measurable, attainable, realistic, and timed appropriately.
Investigator(s)
Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.
Environment
Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.
Specific to this NOFO:
From a CER perspective, evaluate the investigator team's qualifications in terms of experimental design, study execution, data handling, and statistical analyses/interpretation. For a multicenter study, assess whether the organizational structure is appropriate and whether the application identifies a core of potential center investigators with appropriate staffing. Assess whether the proposed sites are sufficient in number and their resources to meaningfully contribute a CER study. Assess whether resources for statistical support are adequate to manage the data and analyses required for CER.
As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, 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, 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 research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals 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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.
As applicable, evaluate the full application as now presented.
As applicable, evaluate the progress made in the last funding period.
As applicable, evaluate the appropriateness of the proposed expansion of the scope of the project.
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.
For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.
Evaluate 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 will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.
Prior to making an award, NIH reviews an applicants federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicants integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.
A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipients business official.
In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk. For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:
All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.
Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. NIH may terminate awards under certain circumstances. See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.
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 (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and 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:
As with any award, even during the period recommended for support, continuation is conditional upon satisfactory progress during both the UG3 and UH3 phases. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NINDS will consider ending support and negotiating a phase-out of the award. The NINDS retains the option to obtain periodic external peer review of progress. Milestones will be established by the NINDS prior to the award of the grant based on recommendations from the primary review group. NINDS may make an award for 2 to 3 years in order to start-up the trial and establish performance feasibility. Continuation of the award past this feasibility period will be contingent upon a demonstrated ability to meet milestones indicating that the trial can be implemented as planned. Feasibility milestones will be defined at the start of each trial and will be monitored closely by the Institute-appointed DSMB and NINDS HLBI Program Official. Achievement of these milestones will be evaluated by NINDS prior to releasing funds for each year of the award and failure to achieve these milestones may lead to trial termination.
Areas of Joint Responsibility include:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.
Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Adam L. Hartman, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
E-mail: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.