National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
U01 Research Project – Cooperative Agreements
See Notices of Special Interest associated with this funding opportunity
The purpose of this notice of funding opportunity (NOFO) is to support rigorous analytical validation of method(s) used for measuring biomarkers for neurological and neuromuscular disorders for use in clinical trials or clinical practice. Applicants must justify the unmet need for the biomarker(s) and measurement methods and specify one or two context(s) of use for the biomarker(s). Activities supported include optimizing and evaluating the accuracy, precision, reportable range, and analytical sensitivity and specificity of the detection method across multiple sites and operators and establishing reference intervals and quality control procedures. Multi-site applications are expected but not required.
This Notice of Funding Opportunity (NOFO) requires a Plan for Enhancing Diverse Perspectives (PEDP).
30 days prior to the 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 21, 2025 | February 21, 2025 | Not Applicable | July 2025 | October 2025 | December 2025 |
June 20, 2025 | June 20, 2025 | Not Applicable | November 2025 | January 2026 | April 2026 |
February 20, 2026 | February 20, 2026 | Not Applicable | July 2026 | October 2026 | December 2026 |
June 22, 2026 | June 22, 2026 | Not Applicable | November 2026 | January 2027 | April 2027 |
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.
IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:
Background
A biomarker is a defined characteristic that is measured as an indicator of a normal biological process, pathogenic process, or responses to an exposure or intervention, including therapeutic interventions. Biomarker modalities are diverse, and can include ‘omics, imaging, behavioral, digital and physiologic endpoints. Because the measurement of the biomarker is integral to defining the biomarker, it is necessary to describe the biomarker in terms of its biological source or matrix, measurable features, and the analytic method used to measure it (detection method).
Biomarkers are critical to the discovery and development of therapeutics and can serve a variety of functions such as verifying therapeutic target engagement, improving trial design by patient stratification, and facilitating clinical care decisions. Despite the active pace of discovery of novel biomarker candidates, few biomarkers progress beyond discovery to the robust analytical and clinical validation needed for use in Phase II and Phase III clinical trials. Thus, there is a critical need to advance validation of biomarkers to improve public health, particularly for disorders of the nervous system where advancing therapeutics from discovery to the market are notoriously challenging. Validation of biomarkers for all neurological and neuromuscular disorders within NINDS mission and across the age spectrum are within scope.
This NOFO is intended to address the gap in biomarker validation by encouraging rigorous analytical validation of the biomarker detection method for one or two specified context(s) of use.
Definitions of terms used in this NOFO:
Biomarker categories as defined in the Biomarkers, EndpointS, and Other Tools (BEST) Resources (https://www.ncbi.nlm.nih.gov/books/NBK338448/) include:
Research Objectives
This NOFO supports research to conduct analytical validation of the detection method for a biomarker or biomarker signature or composite biomarker for one or two specified context(s) of use. Premise for the utility of the biomarker(s) should include evidence that the biomarker/biomarker signature/composite has undergone preliminary testing in an appropriate clinical population, using either prospective or retrospective data or samples, and shows sufficient clinical sensitivity and specificity and/or association with the biological concept of interest to warrant additional investment. In addition, applications to this NOFO should include evidence that the detection method for the biomarker has already been developed and subjected to initial evaluation of precision and analytical sensitivity. This NOFO supports research that clearly describes how the proposed study plans to optimize and standardize the detection method, as well as clearly define and rigorously test the analytic and pre-analytic variables to evaluate and reduce sources of variability when measuring the biomarker.
Earlier stage research that still needs to conduct clinical proof of concept studies to establish the relationship between candidate biomarkers with a concept of interest (with or without detection method development) should consider applying to the companion NOFO, PAR-22-089 Development of Biomarkers or Biomarker Signatures for Neurological and Neuromuscular Disorders. Alternatively, studies that are seeking to conduct final clinical validation research using detection methods that have already been extensively analytically validated for the proposed context of use should consider the companion NOFO Clinical Validation of Biomarkers for Neurological and Neuromuscular conditions.
The Analytical Validation NOFOs and companion Clinical Validation NOFOs are designed to help gather the data package needed for clinical trial readiness and may be used to support a submission to the FDAs Biomarker Qualification Submission or to the FDAs Center for Devices and Radiological Health.
For more information on the Biomarker Qualification program see: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/BiomarkerQualificationProgram/default.htm
Application Characteristics
Although an individual indicator may be useful as more than one category of biomarker (i.e. both diagnostic and monitoring) the type of evidence required to validate it depends on the biomarker category specified; for example, a monitoring biomarker would need to demonstrate robustness in a longitudinal study design whereas a diagnostic may be evaluated at a cross sectional design. Thus, defining the biomarker category(ies) is essential to developing the experimental design and analytical performance necessary to validate it.
Analytical Validation should include, but is not limited to, the following metrics with use of regulatory guidance standards appropriate for the Context of Use
Collaborations
Multi-disciplinary collaboration among scientific investigators, developers, clinicians, statisticians, consultants, and clinical laboratory staff are an integral part of the application. Projects proposed for this NOFO should utilize multi-site design as applicable, with standardized data stewardship to ensure reproducibility and reliability across users and operators.
Investigators are encouraged to form collaborations with individuals knowledgeable in the FDA qualification process as well as those familiar with the process of analytical validation, including statistical design and analysis experts.
Leveraging Existing Resources
Where applicable, applicants are encouraged to leverage existing research resources for their studies. Such resources may include clinical biospecimen samples from the NINDS Human Biospecimen and Data Repository (BioSEND; https://biosend.org/) or other existing biospecimen, imaging and data repositories. Leveraging the resources of ongoing clinical trials or clinical studies supported through other Federal or private funds is also encouraged.
Project Milestones
A project timeline with annual milestones must be included in the application (see Section IV). Milestones should describe project decision points with results-driven, quantitative metrics for go/no-go decision making throughout the funding period.
The NIH Program Official will contact the applicant to discuss the proposed milestones prior to the award. Under this Cooperative Agreement mechanism, NINDS Program Staff will have substantial communication and involvement with researchers in decision-making prior to award and during the conduct of the study to provide oversight of data and safety monitoring, ensure the timely completion of the proposed studies and to maximize the positive impact of the studies on upcoming clinical trials. The Program Officer and Scientific Officer will discuss with the Program Director(s)/Principal Investigator(s) any recommended changes to the research plan or suggestions from peer review, and the plan and milestones may be revised as appropriate prior to the award.
Rigor, Reproducibility, Data Sharing and Intellectual Property
NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/Funding/grant_policy). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.
To improve reproducibility and community uptake, investigators are generally expected to share code/scripts, analytic tools/statistical models, protocols/processes and metadata before the end of the projects period of performance. If there is a plan to commercialize aspects of the project such as analytic software, applicants should consult with their tech transfer office when developing the Data Management and Sharing Plan (DMS Plan) and intellectual property plan. Budgets should reflect any costs associated with these efforts. Information on many available NIH supported or frequently used repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html
Applicants collecting biofluid samples from prospectively enrolled study participants are encouraged to share samples through the NINDS biomarker repository, BioSEND (https://biosend.org/ ) to provide the broader scientific community with a data resource for hypothesis generation and test validation. Applicants should contact BioSEND to incorporate sharing plans and cost in their application.
Pre-Application Consultation
Applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning for an application. This early contact will provide an opportunity to discuss and clarify NINDS policies and guidelines, including the scope of the project relative to the NINDS mission and intent of this NOFO. These discussions can also provide any needed clarification regarding development of an appropriate timeline and milestone plan.
Funding Considerations
Applications within the top scoring meritorious range will be considered for funding. Within that range, priority may be placed on applications that fill a critical program gap to ensure biomarker development that is reflective of the breadth of disorders and conditions within NINDSs mission. Additionally, priority will be given to biomarkers that: 1) address an unmet medical need, 2) are supported by a strong biological rationale, 3) include a carefully designed plan for performance evaluation, 4) include a plan for standardization of samples and data collection for use in validation and 5) provide a strong justification for the utility of the biomarker in the clinical setting or for use in clinical trial design.
Applications Not Responsive to this NOFO
Non-responsive studies include:
Non-responsive applications will be administratively withdrawn without review.
See Section VIII. Other Information for award authorities and regulations.
Plan for Enhancing Diverse Perspectives (PEDP)
The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.
To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.
This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.
The PEDP will be submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance materials.
Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.
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.
Optional: Accepting applications that either propose or do not propose clinical trial(s).
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 should to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the project period. The maximum project period is 4 years.
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 Government
Other
Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the 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.
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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
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:
Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: carol.taylor-burds@nih.gov
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.
Other Attachments:
Timeline and Proposed Milestones (required; 3 pages maximum)
Milestones should describe project decision points with quantitative metrics for go/no-go decision making throughout the funding period. Annual quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties. Milestones will be used to monitor project progress as part of the evaluation for continued funding by the Program Official and Project Scientists.
For each milestone, provide a brief description of the success criteria and justification for those criteria.
Quantitative milestones are dependent on the project but should include items such as:
A Gantt chart for the timeline of attaching each milestone must be included.
Team management plan (required; 3 pages maximum):
All applicants must include a team management plan that describes the workflow of the team/key personnel. Applicants are strongly encouraged to form multidisciplinary teams that consist of clinical scientists, disease/biology matter expertise, statisticians, particularly those with clinical trial design expertise, regulatory expertise, and other academic/industry experts relevant to the modalities used in the application. Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, etc.) over the course of the project and include letters of support (below). This section should be complementary to the Multiple PD/PI Leadership Plan leadership plan by focusing on how the project will be managed across sites, PIs, co-Is and consultants. Effective project management is a critical component of achieving the program goals, especially as the team size increases. Elements to consider include:
Associated clinical trial protocols and consent forms (required if applicable; no page limit): Applications that propose to conduct ancillary studies to clinical trials and/or leverage samples/data collected from previous clinical trials must include the clinical trial protocols and consent forms used in the trials.
Intellectual Property Plan (if applicable; 1 page maximum): Applicants are encouraged to prepare this section in consultation with their institutions' technology transfer officials.
Applicants should describe any constraints of which they are aware that could impede commercialization (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar biomarkers that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program. If the IP of the detection method device/technology/software is owned by an entity other than the applicant's institution, then a letter of support should be obtained indicating there will not be any limitations imposed on the studies or the product which would impede achieving the goals of the funding program. If patents have been filed around the biomarker detection method(s) used in this application, then the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable
Letters of Support (if applicable; no page limits):
If existing biospecimens are to be used, include letters of support or approval for use of those samples, including those banked at BioSEND. For example, if samples include those adjudicated by the Parkinson's Disease Biospecimen Review Access Committee (PD-BRAC), a letter indicating BRAC approval should be included (https://pdbp.ninds.nih.gov/pd-brac)
Plan for Enhancing Diverse Perspectives (PEDP)
Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:
Examples of items that are not appropriate in a PEDP include, but are not limited to:
For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance materials.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
PEDP implementation costs:
Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.
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:
This NOFO supports the validation of analytical methods for biomarker measurements, including evaluation of the detection method, its performance characteristics, and the optimal conditions that will generate reproducibility and accuracy consistent with FDA guidelines that are fit for the purpose of the detection method.
Context of Use and Specific Aims
Context of Use: briefly describe the contexts of use which must include both the BEST biomarker category and the biomarkers intended use in therapeutic development or clinical practice (no more than two contexts of use should be included).
Specific Aims Briefly describe the project aims, including the technical questions to be answered and the performance outcomes and characteristics needed in order to be used for the stated Context of Use(s). A scientific hypothesis is not required for this type of application.
Research Strategy
The Research Strategy Section should include the following sections and address the following topics:
Clinical Context and Unmet Need:
Premise, Biological Rationale and Technical Readiness:
Approach and Statistical Analysis Plan:
If an application proposes to use only a single site for analytical validation, then a short paragraph with the heading justification for single site analytical validation must be included to justify why a multisite setting is unnecessary or impossible (such as for rare diseases/conditions that can only be diagnosed or treated in a few specialized settings)
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.
Applicants planning to collect biofluid samples from prospectively enrolled study participants should also provide the broader scientific community with a biofluid sample resource for hypothesis generation, test validation, and discovery related through the NINDS biomarker repository, BioSEND (https://biosend.org/). Applicants should contact BioSEND to incorporate sharing plans and cost in their application. Note that costs for collection are NOT included as a component of the NINDS Biomarkers Repository award.
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.
The Appendix should include the following, as appropriate for the proposed study:
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.
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.
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. 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, 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.
Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.
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.
Requests of $500,000 or more for direct costs in any year
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 grantdisclosures@oig.hhs.gov.
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. As part of the overall impact score, reviewers should consider and indicate how the plan to enhance diverse perspectives affects the scientific merit of the project.
Reviewers will consider 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 factor score.
Significance
Innovation
Specific to this NOFO
Approach
Rigor:
Feasibility:
Specific to this NOFOs:
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.
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Specific for this NOFO:
Protections for Human Subjects
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.
Vertebrate Animals
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.
Biohazards
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.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
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.
Authentication of Key Biological and/or Chemical Resources:
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, consistent with applicable law.
Please note that reviewers will not consider race, ethnicity, age, or gender of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its 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.
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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.
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).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
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:
Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
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 recipients and NIH staff as described above.
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between 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: GrantsInfo@nih.gov (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: support@grants.gov
Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: carol.taylor-burds@nih.gov
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: nindsreview@nih.gov
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS))
Email: ChiefGrantsManagementOfficer@ninds.nih.gov
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.