Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
See Notices of Special Interest associated with this funding opportunity
This funding opportunity announcement (FOA) encourages the development and validation of animal models and human/animal tissue ex vivo systems that recapitulate the phenotypic and physiologic characteristics of a defined neurological or neuromuscular disorder. The goal of this FOA is to promote a significant improvement in the translational relevance of animal models or ex vivo systems that will be utilized to facilitate future development of neurotherapeutics. Ideally, models proposed for this FOA would have the potential to provide feasible and meaningful assessments of efficacy following therapeutic intervention that would be applicable in both preclinical and clinical settings. This FOA is part of a suite of Innovation Grants to Nurture Initial Translational Efforts (IGNITE) Program focused on enabling the exploratory and early stages of drug discovery.
Not Applicable
Application Due Dates | Review and Award Cycles | ||||
New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
June 17, 2021 | June 17, 2021 | Not Applicable | October 2021 | January 2022 | February 2022 |
October 19, 2021 | October 19, 2021 | Not Applicable | February 2022 | May 2022 | June 2022 |
February 22, 2022 | February 22, 2022 | Not Applicable | June 2022 | October 2022 | November 2022 |
June 21, 2022 | June 21, 2022 | Not Applicable | October 2022 | January 2023 | February 2023 |
October 18, 2022 | October 18, 2022 | Not Applicable | February 2023 | May 2023 | June 2023 |
February 21, 2023 | February 21, 2023 | Not Applicable | June 2023 | October 2023 | November 2023 |
June 20, 2023 | June 20, 2023 | Not Applicable | October 2023 | January 2024 | February 2024 |
October 20, 2023 | October 20, 2023 | Not Applicable | February 2024 | May 2024 | June 2024 |
February 20, 2024 | February 20, 2024 | Not Applicable | June 2024 | October 2024 | November 2024 |
| June 20, 2024 | June 20, 2024 | Not Applicable | October 2024 | January 2025 | February 2025 |
| October 21, 2024 | October 21, 2024 | Not Applicable | February 2025 | May 2025 | June 2025 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
New Date October 22, 2024 per issuance of NOT-NS-24-048. (Original Expiration Date: July 13, 2024)
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Background
Optimization of novel therapeutics is usually dependent upon preclinical evaluation in animal models or ex vivo model systems (referred to as simply models for this FOA). This FOA is intended to support the development of validated and clinically relevant animal models, and/or ex vivo model systems. These models should translate to the clinical setting to the degree that they can inform the decision to advance a therapeutic candidate to clinical testing and can inform clinical study design.
Animal models and ex vivo model systems should represent a significant advance over those that currently exist for a defined neurological or neuromuscular disease/disorder. They can include genetic, chemical, and/or physiological manipulations in animals or ex vivo systems that recapitulate a significant component (clinical manifestations and underlying physiology) of the disease condition in humans. Animal models should be compatible with endpoints that are measurable and relevant to the disease process in both preclinical and clinical settings.
Development of models that translate to a human disorder or disease requires rigorous internal and external validation. In order to demonstrate internal validation, it is important to evaluate and understand the precision, reliability, sensitivity, accuracy, and dynamic range characteristics of the endpoints used to assess the effect of therapeutic or physiological intervention in the animal model or model system. In addition, it is essential that the general experimental design procedures utilized in characterizing the model are conducted in a rigorous manner, utilizing randomization, blinding and the appropriate power analysis.
It is also important to address external validation, showing that the model can recapitulate aspects of the disease phenotype and etiology, where endpoints or biomarkers of disease are similar and measurable in both the model system and in human disease. One component of external validity is face validity-the similarity between the model and the clinical manifestation of the disease (as measured by overt clinical symptoms, patterns of activation using fMRI or EEG, functional or behavioral read-outs, disease progression, etc.). Another component of external validity is construct validity--the similarity between the physiological or biological basis of the model and the actual human disorder (i.e., genetic, proteomic, metabolomic markers).Although components of both face and construct external validity are certainly desirable in a model, predictive validity provides the most confidence in the ability of the model to translate to human disease. Predictive validity refers to the probability that a clinically validated therapeutic (biologic, small molecule, device, surgical procedure, etc.) will have the same effects in the model as it will in the intended clinical population. By definition, the evaluation of predictive validity requires a validated tool/therapeutic that has been shown to alter disease progression in humans. Note that experimental therapeutics cannot be used to validate an experimental model. Predictive validation of the model requires a validated tool/therapeutic with a known effect in humans. Since these tools do not necessarily exist for many neurological diseases, it is not always possible to obtain true evidence of predictive validity until the candidate therapeutic is actually tested in humans. Therefore, it may not always be possible to evaluate the predictive validity of a new animal model or ex vivo model system. However, it is important to include evaluations of internal validity, and face, construct, and predictive validity (to the extent possible), to provide evidence that the proposed model represents a significant advance over existing models.
FOA Scope
The FOA will support applications to develop animal models of neurological or neuromuscular disease that recapitulate aspects of the disease pathophysiology as well as its etiology, where endpoints or markers of disease are similar and measurable in the animal model and human disease (i.e., neurological deficits, patterns of activation using functional Magnetic Resonance Imaging (fMRI) or electroencephalography (EEG), measurable genetic markers, functional or behavioral read-out, disease progression, etc.). The FOA will also support the development of non-genetic models (i.e., motor function, physiological manipulations such as artificial vessel obstruction or diet) that expose disease symptoms in animals and humans. In addition, it will support the development and validation of ex vivo testing systems that utilize existing human or animal cell systems (i.e., induced Pluripotent Stem Cells (IPSC)).Applications for use or development of iPSCs should consult NOT-NS-14-032.Since this FOA does not support the development of animal models or model systems for the purpose of testing hypotheses about disease etiology, it is assumed that model development will be based upon widely accepted hypotheses or knowledge regarding disease etiology.
The knowledge gained from these studies should lead to the development of "next generation" translational models of neurological disease. The models developed and validated as a result of applications to this FOA should provide an improved translational toolkit that will better predict the efficacy and safety of new therapeutic entities, thereby facilitating future drug discovery and development in the field of neurological disorders and stroke.
Applications that propose to validate existing models are also appropriate for this FOA. However, development of de novo models without validation is not appropriate for this FOA.
Phased Award Mechanism and Transition to R33
The identification and characterization of clinically relevant preclinical models typically require a multi-step process that includes initial feasibility testing of the model system followed by internal and external validation. Therefore, this funding opportunity will use a phased R61/R33 mechanism. The R61 phase will support initial development, internal validation and optimization of the model. The R33 phase will support any required scaling along with external validation studies. The final outcome should be a fully validated model that can be utilized in both preclinical and clinical settings to test the biological effects of candidate therapeutics designed to treat neurological disease. Transition from the R61 to the R33 phase is contingent upon the successful completion of proposed milestones. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision making at the R61/R33 transition point and should have timelines and quantitative criteria associated with them. All milestones should be useful as a measure of progress toward the overall goal of the project (see Section IV). NINDS emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress. Specific Aims or a list of activities planned for each year are not considered milestones because they do not provide decision-making goals. For frequently asked questions and milestone examples, please see https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/Funding-Programs-Researchers/IGNITE.
Examples of activities in the R61 Phase include, but are not limited to:
Examples of activities in the R33 Phase include, but are not limited to:
Collaborations:
Demonstration of collaborative relationships between applicants with preclinical and clinical drug development expertise (such as biostatisticians and clinicians) is highly encouraged. It is preferred that the collaborating clinician is listed as a co-investigator or a formal member of the investigative team. Alternatively, a letter of support from the collaborating clinician can be used to demonstrate involvement in the project but should include a plan for collaboration with the principal investigator. The clinician should have demonstrated experience in the development of therapeutic entities to treat neurological disease.
In addition, applicants should strive to increase the diversity of their teams. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Please see NIH NOT-OD-20-031 for details.
Applications Not Responsive to this FOA:
Non-responsive studies include those that involve any of the following activities:
Studies that fail to include quantitative, go/no-go milestones as well as a clear demarcation of which activities are in the R61 phase and which are in the R33 phase are also considered non-responsive. Non-responsive applications will be administratively withdrawn without review.
Additional Considerations
Applicants are strongly encouraged to contact Scientific/Research staff to discuss potential research projects prior to submitting an application.
Small Business applicants who are eligible for the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are strongly encouraged to submit through either the SBIR or STTR Omnibus Solicitations (https://sbir.nih.gov/funding#omni-sbir) or other appropriate SBIR or STTR funding opportunity to take advantage of the congressionally mandated set-aside specifically for small businesses. Please see https://www.ninds.nih.gov/Funding/Small-Business-Grants for more information about the programs.
Prior to funding an application, NINDS Program staff may contact the applicant to discuss the proposed milestones and any changes suggested by the NINDS review panel or Program staff. A final set of approved milestones will be specified in the Notice of Award.
For more information about other NINDS Translational Programs visit the website https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research.
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Direct Costs cannot exceed $499,000 in any one year and cumulative direct costs for the three year project cannot exceed $750,000.
The total project period for a combined R61/R33 application submitted in response to this FOA may not exceed three years, with no more than two years for the R61 phase and no more than two years for the R33 phase.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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. 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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Attachments:
Intellectual Property (IP): Applications can include an Intellectual property (IP) strategy, if appropriate. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials.
Applicants should describe the IP landscape surrounding their model, if applicable. Applicants should describe any known constraints that could impede their discovery and development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar model systems 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 applicant proposes using a technology or agent(s) for validation purposes whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should include a letter (see letter of support) from any entities owning the IP 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 pertinent to the model technology or validating agent(s) being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable.
Applicants should discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved, consistent with achieving the goals of the program.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Within the Specific Aims section, include headers titled R61 Phase Specific Aims and R33 Phase Specific Aims. Under each header, state the specific objectives of the efforts. Briefly provide the context and overall rationale for the proposed set of studies, with an emphasis on the reason that the proposed model will significantly improve the translational quality of existing tools in the specified neurological disease area. In addition, the major objectives of the proposed set of studies should be stated, including the technical questions to be answered to determine the feasibility and the validity of the proposed model systems relative to the end goal of a clinical setting.
As this is an R61/R33 mechanism, clear demarcation of which activities are in the R61 and which are in the R33 is required (the two phases should not overlap in time). Applications that do not propose both an R61 and R33 phase will be administratively withdrawn without review.
Research Strategy: The Research Strategy section should include the following sections:
Milestones
Transition from the R61 to the R33 phase is contingent upon the successful completion of one set of proposed milestones. The specific milestone(s) proposed in the application will depend on the goals of the application and the accomplishments necessary in the R61 phase for advancement into the scaling and validation studies proposed for the R33 phase. These milestones are to be included as the last element of the Research Strategy section of the application and will be evaluated as part of the scientific and technical merit of the R61/R33 application. The milestones proposed in the application should be well-described, quantifiable, and scientifically justified to allow program staff to assess progress in the R61 phase. In addition, milestones should reflect the objectives of the application and be appropriate for the indication. Rationale should be provided for the choice of measures and values proposed for the milestones. Specific aims or a list of activities is not considered milestones because they would not provide decision-making goals. A discussion of the milestones relative to the progress of the R61 phase and the implications of successful completion of the milestones for the R33 phase should be included. The clarity and completeness of the R61/R33 application with regard to specific goals and feasibility milestones are critical. Milestones should provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application as part of the consideration of the awarded project for further funding of non-competing award years by the Program Director(s)/Principal Investigator(s), and Program Official. The existence of clear, quantitative, go/no-go milestones for transition from the R61 to the R33 phase is a requirement for this FOA. Applications lacking milestones will be administratively withdrawn without review. Potential applicants with questions about suitable milestones are encouraged to contact NINDS program staff prior to application. Example milestones can be found at https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/IGNITE-Milestone-Examples.
Timeline
Provide a timeline with specific milestones for progression from the R61 phase to the R33 phase. The timeline, specific goals and feasibility milestones should be clear and complete. Indicate when it is anticipated that essential components of the project will be completed. The proposed timeline with specific milestones should be clearly delineated and should appear as the last element of the Research Strategy section.
Collaboration
NINDS strongly encourages applicants to form multidisciplinary teams that consist of academic/industry experts relevant to the research plan (i.e., biostatisticians, clinicians, technical experts). This multidisciplinary team should be able to define the goals of the research, outline specific gaps that need to be addressed during this funding period, outline detailed plans and experiments, and execute the research strategy.
NINDS strongly encourages applications from diverse teams of investigators, including PI/PDs and team members that are underrepresented in the biomedical workforce (defined in NIH NOT-OD-20-031).
Letters of Support: Applicants should include a letter of support from a clinical collaborator, as described in Part 2, Section I. The letter of support should outline a collaboration plan between the preclinical and clinical applicants. The collaboration plan should include the roles and responsibilities of the preclinical and clinical scientists in developing the model as it relates to the pathophysiology and/or disease etiology of clinical populations typically recruited in drug development programs focused on a specific neurological disease. The plan should also address the feasibility of endpoint measures in preclinical and clinical settings, along with the strategy for external validation.
Applicants should include letters of support from consultants, contractors, and collaborators.
If applying from an academic institution, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.
If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
If collaborating with a private entity, include a letter of support that addresses any agreement to provide agent(s), any limits on the studies that can be performed with said agent(s), any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place. This letter should come from a high official within the private entity who has authority to speak on these issues.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the 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.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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 review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Further criteria specific to this opportunity: Is there potential for the model to translate to human disease? Have the investigators carefully considered the phenotype, physiology, and feasibility of measurement of the targeted clinical population in the design and validation of their preclinical model system? Does the model have feasibility and utility from both preclinical and clinical perspectives? Is there strong rationale of unmet need for the model in the defined neurological disease area? Has the investigator carefully considered the role of the model in the drug discovery and development process? What is the overall potential for the proposed studies to substantially advance translational medicine and drug development in the disease area described?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Further criteria specific to this opportunity: Are the investigators knowledgeable and experienced about the biological target and/or disease biology? Do the investigators have sufficient expertise in the areas of in vivo or ex vivo pharmacology, experimental design, statistical analysis, systems analysis, etc. (as appropriate) for the project? Have they formed collaborations with clinicians who have drug development experience? Is there evidence that the clinical collaborator will play an active role in the design and validation plans of the models? Are the roles of all collaborators carefully defined in the research plan?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Further criteria specific to this opportunity: Has the application included adequate plans to optimize the model (if necessary)? Have plans to estimate the feasibility of the model for validity been carefully considered?
Are plans for model validation (both internal and external validation) clearly described with sufficient detail? In the case of endpoint measures, have methods for addressing internal validity characteristics such as dynamic range, precision, accuracy, etc., been adequately addressed? Is the proposed statistical analysis appropriate for the experimental design and the quantitative characteristics of the endpoints? Have methods for evaluating external validity characteristics (how well the model system recapitulates human clinical symptoms, pathology, physiology and genetic basis for disease) been systematically outlined in the application for model characterization?
Has the applicant thoughtfully considered the potential to produce a model that will be feasible to implement and will meaningfully translate to human biology? Does the application show an understanding of the state of the field and where the proposed model contributes to the field?
Does the application make a compelling case that the strategy proposed is distinct from and more likely to support therapy development compared to other models?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Milestones and Timelines
Are milestones robust and associated with clear, quantitative criteria for success that allow go/no-go decisions at the R61/R33 transition point? If criterion is not to be used for go/no-go decisions is it justifiable?
Does the set of milestones allow the evaluation of progress in the R61 phase and will successful completion of these milestones provide confidence that the investigator will be able to successfully implement the R33 phase? Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without unnecessary steps?
Are the milestones and approach proposed scientifically justified and appropriate to address the questions and objectives of the application?
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, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Renewals
Not Applicable
Revisions
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
Intellectual Property (IP) Strategy
It is not anticipated that IP will necessarily have to be filed for a model. Does the application outline any known constraints that could impede the model from being developed (e.g., certain restrictions under transfer or sharing agreements, etc.) and how these issues could be addressed while achieving the goals of the program? If IP will be shared among co-investigators, is a clear plan in place for sharing of the IP that will set the project up for success beyond IGNITE?
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
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.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website. For NINDS analysis and tracking purposes, all no-cost extension requests will require prior NIH approval.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the 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.
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.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
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: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Becky Roof, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: [email protected]
Chief, Scientific Review Branch
National Institute for Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Chief Grants Management Officer
National Institute for Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.