National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
See Notices of Special Interest associated with this funding opportunity
The purpose of this Notice of Funding Opportunity (NOFO) is to promote the development of fit-for-purpose candidate biomarkers and composite biomarker that enable more efficient clinical trials advance therapeutic development or clinical practice help guide clinical care decisions. Specifically, the goal of this phased funding mechanism is to first identify or confirm candidate biomarker(s) or biomarker signatures using human samples and/or data, followed by an independent retrospective or prospective clinical study to conduct initial clinical validation of the biomarker/signatures clinical utility for one or two defined Context(s) of Use. In the first phase, applicants are expected to demonstrate that the biomarker acceptably identifies or predicts the concept of interest and may include optimization of the detection method using carefully standardized human samples or datasets. The overarching purpose of this initiative is to deliver candidate biomarkers or biomarker signatures that are ready for definitive analytical and clinical validation studies.
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 | May 07, 2025 * | July 2025 | October 2025 | December 2025 |
June 20, 2025 | June 20, 2025 | September 07, 2025 * | November 2025 | January 2026 | April 2026 |
October 20, 2025 | October 20, 2025 | January 07, 2026 * | March 2026 | May 2026 | July 2026 |
February 20, 2026 | February 20, 2026 | May 07, 2026 * | July 2026 | October 2026 | December 2026 |
June 22, 2026 | June 22, 2026 | September 07, 2026 * | November 2026 | January 2027 | April 2027 |
October 20, 2026 | October 20, 2026 | January 07, 2027 * | March 2027 | May 2027 | July 2027 |
February 22, 2027 | February 22, 2027 | May 07, 2027 * | July 2027 | October 2027 | December 2027 |
June 21, 2027 | June 21, 2027 | September 07, 2027 * | November 2027 | January 2028 | April 2028 |
October 20, 2027 | October 20, 2027 | January 07, 2028 * | March 2028 | May 2028 | July 2028 |
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:
Purpose
The purpose of this Notice of Funding Opportunity (NOFO) is to conduct proof of concept biomarker discovery and development studies followed by preliminary clinical validation to evaluate if the candidate biomarker or composite biomarker may be fit-for-purpose for use in clinical trials or clinical practice. This NOFO uses a phased R61/R33 mechanism in which the R61 phase is used to test a hypothesis regarding the candidate biomarker or composite biomarkers relationship to the biological concept of interest and may also be used to develop or optimize the method for measuring the biomarker or composite biomarker (the method of detection). The R33 phase is to conduct the preliminary clinical validation to test the utility of the biomarker or biomarker signature for one or two specified Context(s) of Use. Applications should directly address how the candidate biomarker(s) or biomarker signature would fill an unmet need (i.e. better reliability, more cost-effective, significantly improved sensitivity and specificity, etc.) and how the biomarker/composite would be an advantage over existing standards. The Context(s) of Use should be carefully considered and clearly described as studies are expected to directly test the candidate biomarker or composite biomarker for one or more Context of Uses in the R33 phase. Biomarkers are used to make decisions at the level of the individual patient or person; therefore, the study design and analyses proposed are expected to establish initial decision-making criteria for how the readout of the biomarker result would be used for the proposed context of use. The rationale for the proposed studies should be supported by strong biological plausibility linking the candidate biomarker or composite with the pathophysiological process(es) of interest. Applications focused on understanding biological mechanisms, networks, or other fundamental knowledge rather than focused on developing biomarkers for use as a clinical trial tool or for use in clinical practice to help guide clinical care decisions are not appropriate for this funding opportunity. Projects that successfully complete both the R61 and R33 phases should meet the entry criteria for the later stage Analytical and Clinical Validation PARs.
Background
A biomarker is a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes or responses to an exposure or intervention, including therapeutic interventions. A composite biomarker is a combination of multiple variables analyzed to yield a patient-specific indicator of normal biological processes or response to an exposure or intervention including therapeutic interventions. Biomarker modalities are diverse, and can include genomic, transcriptomic, proteomic, histologic, metabolomic, imaging, behavioral, physiologic and digital measures.
Biomarkers are critical to the discovery and development of therapeutics. For example, they can serve as indicators of therapeutic target engagement and pharmacodynamic (PD) response and provide an early signal of treatment response in a clinical trial. Biomarkers can also improve the efficiency of clinical trials by stratifying patients to reduce the impact of the variability associated with phenotypic heterogeneity. In addition, biomarkers allow the evaluation and monitoring of therapeutic intervention on disease progression or recurrence, as well as on the clinical manifestation of disease phenotype or severity. Finally, biomarkers are important tools in the evaluation of susceptibility and risk for developing a disease or disorder, thereby improving early diagnosis and therapeutic outcomes in cases where disease or disorder manifestation could be significantly attenuated or prevented with treatment.
Despite the active pace of discovery of novel biomarker candidates, few biomarkers progress into clinical use, and robust, well-validated biomarkers for use in Phase II clinical trials remain scant. Thus, there is a critical need to advance biomarkers to improve clinical research and therapeutic development, particularly for diseases and disorders of the nervous system where failures to advance therapeutics remains a challenge. While many candidate biomarkers may represent pathophysiological processes that be useful in a variety of contexts, studies are needed to evaluate and validate candidate biomarkers within the context they are proposed to be used to establish the evidence needed to inform decision making at the participant or patient level. The goal of this NOFO is to promote a rigorous early evaluation of the candidate biomarkers and composite biomarkers for use as fit-for-purpose tools in clinical trials or in clinical practice.
Phased Award Mechanism Research Objectives and Transition to R33 Phase
This funding opportunity uses a R61/R33 Phased Innovation Award mechanism. The R61 phase will support biomarker and biomarker signature proof of concept studies to test a hypothesis that a candidate biomarker or biomarker signature is an indicator of a particular concept (a biological process or response to an intervention). Studies must use clinical samples, tissues, and/or data to evaluate the candidate biomarker or biomarker signature (animal studies are not allowed). Studies may also include optimization or additional development of the detection method including preliminary analytical validation needed to measure the biomarker/composite. The purpose of the R33 phase is to conduct preliminary clinical validation of the biomarker or composite biomarker for a specified Context of Use. Context of Use should include defining the category of biomarkers defined in the Biomarkers, EndpointS, and other Tools (Biomarkers, EndpointS, and other Tools (BEST) Resource and how it will be measured and used in clinical trials or clinical practice. Transition from the R61 to the R33 phase is contingent upon the successful completion of Go/No-Go milestones. The milestones should include pre-specified quantitative metrics that demonstrate the construct validity of the biomarker(s) and the concept of interest to demonstrate potential clinical utility, as well as the sensitivity, specificity, and internal validity of the detection method to measure the biomarker or signature. Milestones must be clearly defined, quantifiable, and scientifically justified to allow the investigator and program staff to assess progress in the R61 phase (Please refer to Project Milestones, end of Section I). Completion of a research project resulting from successful application to this NOFO should result in a candidate biomarker or biomarker signature that meets the entry criteria for the companion NOFOs supporting definitive analytical validation of the detection method (PAR-24-095, PAR-24-098)) or definitive clinical validation (PAR-24-097, PAR-24-096).
The definitions of terms within this NOFO:
Project Characteristics
The biomarker or biomarker signature must be focused on a neurological or neuromuscular disease or disorder within the NINDS mission.
Applications are expect to provide:
Examples of Biomarker or Biomarker Signature Studies Supported in this NOFO Include, but Are Not Limited to:
The R61 phase may include preliminary Analytical Validation of the detection method including metrics such as:
The R33 phase may include preliminary Clinical Validation of the biomarker or signature including metrics such as:
Non-Responsive Studies
Investigator Team Characteristics
Multidisciplinary teams are necessary for successful development of candidate biomarkers and biomarker signatures. Areas of expertise needed include biomarker development, clinical expertise relevant for the clinical populations of interest, statistical and/or bioinformatics analysis, experience with the use and development of the detection method technology, biosample, data or tissue source standardization, and biological expertise in the disorder/disease pathophysiology. Investigators are encouraged to form collaborations and seek additional consultants as needed for the project.
Considerations for clinical trials
Studies meeting the NIH definition of a clinical trial are allowed when the primary intent is to evaluate the biomarker relative to the intervention of interest, however clinical trials are not supported if the primary intent is to evaluate the intervention's safety, tolerability, clinical efficacy, effectiveness, and/or clinical intervention and management. For the reasons outlined above, this NOFO typically supports only mechanistic types of clinical trials (Basic Experimental Studies Involving Humans (BESH)).
Leveraging Existing Research Resources
Applicants are strongly encouraged to leverage existing NINDS and NIA research resources for their studies whenever possible (https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html). Such resources may include tissue, cellular, or DNA samples from NINDS BioSEND (https://www.biosend.org/) or other existing biospecimen, imaging and data repositories, such as the NINDS Human Cell and Data Repository (https://nindsgenetics.org/), The Federal Interagency Traumatic Brain Injury Research (FITBIR) informatics system, the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD; https://ncrad.iu.edu/) and the Accelerating Medicines Partnership for Alzheimer's Disease (https://adknowledgeportal.synapse.org/) and Accelerating Medicines Partnership for Parkinson's Disease (https://amp-pd.org/). The NINDS BioSEND repository receives, processes, stores, and distributes biospecimen resources from NINDS funded studies that can be shared by the neuroscience research community, and currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva. The NINDS Human Cell and Data Repository provides 1) disease-relevant stem cell lines for biomarker discovery, and/or 2) the capacity to bank blood for the creation of new cell lines relevant to their disease of interest. Leveraging the resources and support from neurological disorder advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program are also encouraged. Finally, applicants are encouraged to leverage the resources of ongoing clinical trials supported through other Federal or private funds.
Applications proposing to collect biospecimens are strongly recommended to use the NINDS Biomarkers Repository BioSpecimen Exchange for Neurological Disorders (BioSEND) protocols and procedures, and all specimens collected and banked with BioSEND must come from individuals who have consented to banking and sharing broadly with academia and industry.
Note that costs for collection are NOT included as a component of the NINDS Biomarkers Repository award. Therefore, most costs for the biospecimen banking are borne by the recipients utilizing this resource (see NOT-NS-15-046). Applicants planning projects in which biospecimens will be collected are strongly advised to consult the NINDS Biomarkers Repository website for more information about samples banked at the repository (https://www.biosend.org). In addition, applicants are advised to consult with NINDS Biomarkers Repository staff to obtain a quote for biospecimen banking costs (email: biosend@iu.edu).
Pre-Application Consultation
Applicants are strongly encouraged to consult with NIH Scientific/Research 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 or NIA mission and intent of this NOFO. In order to learn more about this NOFO and to have the opportunity to ask questions, a pre-application informational webinar is held at least once a year (usually in December and/or April) and the recordings are posted online at: https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research under the News & Events section.See also Applicant Webinar information under Section IV.7 below ("Other Submission Requirements and Information").
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.
Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
New
Resubmission
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.
The R61 phase can be from 1-3 years and the R33 phase can be 1-3 years, with a total project duration of no more than 5 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 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.
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, Ph.D
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-451-4551
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.
Timeline and Proposed Milestones(required, 1-2 pages maximum):
Intellectual Property Plan (if applicable, 1 page maximum):
Applications should include an Intellectual property (IP) strategy unless the products are intended to be provided as open source tools. Applicants are encouraged to consult their institution's technology transfer officials when preparing this section of the application.
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:
Specific Aims:
Briefly provide the context for the proposed candidate biomarker or biomarker signature along with a cogent argument outlining its importance and unmet need. Briefly describe the hypothesis and biological rationale that the candidate biomarker or biomarker signature to be measured reflects the relevant biological, physiological, or pathological pathway(s) relevant to the clinical concept(s) of interest. Within the Specific Aims section, include headers titled R61 Phase Specific Aims and R33 Phase Specific Aims. Under each header, state the specific aims of the efforts for each phase of the study. State the major objectives of the aims including the technical questions to be answered to further develop and evaluate the biomarker or biomarker signature.
Research Strategy:
The Research Strategy Section should include:
1. Clinical Context and Unmet Need:
2. Premise and Biological Rationale:
3. Approach and Experimental Design:
Letters of Support:
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.
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.
Applicants proposing to collect samples from subjects are encouraged to provide the following information in the Appendix:
Study Protocol, Consent Forms
For Ancillary studies:
IRB approval of the informed consent forms is not required at the time of submission of the application. However, drafts of informed consent forms must be included.
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.
In order to learn more about this NOFO and to have the opportunity to ask questions, a pre-application informational webinar is held at least once a year (usually in December and/or April) and the recordings are posted online at: https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research under the News & Events section.
Information on how to register for the webinar is posted on the NINDS Events page: https://www.ninds.nih.gov/news-events/events?page=1 under Technical Assistance Webinar: NINDS Translational Biomarker Funding Opportunities
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 NINDS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive 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 grantdisclosures@oig.hhs.gov.
Applicants are required to follow the instructions for post-submission materials, as described in the policy
In addition, the Scientific Review Officer (SRO) will accept regulatory meeting minutes and transcripts, and patents, not later than 30 calendar days prior to the peer review meeting.
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.
This NOFO supports studies focused on the identification and development of promising candidate biomarkers or biomarker signatures for neurological and neuromuscular disorders/diseases that will withstand rigorous validation to become tools necessary for the development of neurotherapeutics or for use in treatment decisions within clinical practice.
Priority will be given to biomarkers or biomarker signatures and associated detection methods that: 1) address an unmet medical need for the neurological or neuromuscular disorder/disease specified, 2) are supported by a strong biological rationale for the biomarker and the technology concept, 3) include a carefully designed plan for data and sample collection that is supported by a strong biological and statistical rationale, 4) include a well thought-out plan for development and evaluation of detection technology that carefully considers the feasibility of the detection method for use in a clinical trial setting or clinical practice, 5) include a rigorous plan for biological proof of concept and 6) have the potential to produce a candidate biomarker that can withstand rigorous prospective analytical and clinical validation studies.
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 NOFO:
Investigator(s)
Environment
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.
Specific to this NOFO:
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
As applicable, evaluate the full application as now presented.
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
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), 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.
The review will be convened by the National Institute for Neurological Disorders and Stroke (NINDS).
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.
Not Applicable
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.
At the end of the R61 Phase applicants must include a detailed report including rigorous data on how the milestones have or have not been met. Additional information including protocols may be requested.
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.
At the end of the R61 Phase, PIs may be asked to participate in a R61/R33 Transition Review call where they will be asked to present the progress towards meeting the Go/No-Go milestones and overall progress of the project to NINDS Program Staff including the Program Officer and one or more subject matter experts. This meeting will be used to help clarify and questions from the progress report and may be used to help contextualize the funding recommendation for the R33 phase to NINDS leadership.
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 Ph.D
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)
Telephone: 301-496-9223
Email: nindsreview@mail.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.