- March 12, 2021 - This PAR has been reissued as PAR-21-122.
- November 9, 2020 - Notice of Intent to Publish a Funding Opportunity Announcement for Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Neurotherapeutic Agent Characterization and In vivo Efficacy Studies (R61/R33 Clinical Trial Not Allowed). See Notice NOT-NS-21-006.
- March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077.
- August 23, 2019 - Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137.
- July 26, 2019 - Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128.
- November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications. See Notice NOT-OD-18-228.
Key Dates
apply, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.
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
.The first AIDS date Application Due Date for this FOA is September 7, 2018.
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 March 12, 2021 per issuance of PAR-21-122. (Original Expiration Date: May 08, 2021)
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This FOA provides funding to conduct pharmacodynamic, pharmacokinetic, and in vivo efficacy studies to demonstrate that proposed therapeutic agent(s) have sufficient biological activity to warrant further development to treat neurological disorders. Therapeutic agents may include but are not limited to small molecules, biologics or biotechnology-derived products. It is expected that upon completion, investigators will have sufficient evidence of target engagement and/or in vivo efficacy for selected therapeutic agent(s) to meet the entry criteria for the NINDS Cooperative Research to Enable or Advance Translational Enterprises program for Biologics (CREATE Bio) or the Blueprint Neurotherapeutics Network (BPN). Information on these programs can be found on the NINDS Division of Translational Research website.
In preclinical efficacy studies, a combination of in vivo efficacy, pharmacodynamic (PD) and pharmacokinetic (PK) measures are warranted to determine the feasibility of candidate therapeutic agent(s) to serve as a starting point for further therapy development. Combined measures of PK and PD greatly increase the understanding of the in vivo efficacy of the therapeutic agent(s) by exploring the relationship between the concentration of the agent(s) at the site of action and the resulting efficacy measures. For the purposes of this FOA, in vivo efficacy measures reflect the effects of the therapeutic agent on endpoints that are closely tied to the desired clinical endpoints, but do not necessarily reflect target engagement. While PD measures may also reflect the effects of the therapeutic agent on endpoints closely tied to the desired clinical endpoint, they must also reflect target engagement.
Pharmacodynamic studies may include but are not limited to determination of 1) target occupancy (e.g., binding) and 2) proximal target activation (i.e., signal transduction, neurotransmission, protein synthesis, and gene regulation and transcription). Examples of target occupancy studies may include but are not limited to Positron Emission Tomography (PET) and Single-Proton Emission Computed Tomography (SPECT). In addition to the examples of proximal target activation listed above, more remote measures of target activation may also be considered, for example (but not limited to): ex vivo studies of ion channel function, EEG modulation, or changes in cerebral blood flow or metabolism as measured by fMRI.
Pharmacokinetic measurements reflect the body’s effect on the absorption, metabolism, distribution and excretion of the therapeutic agent. This funding opportunity is intended to support projects with a strong biological rationale including: 1) evidence that the therapeutic agent(s) has the potential to be therapeutically viable, 2) evidence to support the robustness of the pharmacodynamic measures and/or in-vivo efficacy models, 3) a description of the unmet need for the therapeutic agent(s), and 4) a clear justification for how the findings from these studies are relevant to treatments for disorders that are within the NINDS mission. Studies proposed must be part of a well-thought out and clearly defined therapeutic discovery plan.
This FOA uses the R61/R33 Phased Innovation Award mechanism. The R61 phase will support planning and preparation and the R33 phase will support execution of the pharmacodynamics and/or in vivo efficacy studies. Transition from the R61 to the R33 phase is contingent upon the successful completion of one set of proposed milestones. The specific milestones proposed in the application will depend on the entry stage, prior information on the therapeutic agent(s), and the goals of the application. The milestones should be clearly defined, quantifiable, and scientifically justified to allow the investigator and program staff to assess progress in the R61 phase. (For frequently asked questions and milestone examples, please see http://www.ninds.nih.gov/funding/areas/translational_research/ignite.htm )
Entry Criteria
- Novelty: This FOA seeks to apply new knowledge around targets, mechanisms, pathways or therapeutic indications. Projects should aim to develop or re-purpose therapeutics that are significant improvements over existing therapeutics for neurological disorders.
- Biological rationale and preliminary data: Projects funded through this opportunity must have a strong biological rationale for the intended approach, along with preliminary data or literature-based evidence supporting the feasibility and importance of the approach. Preliminary data should be from well designed experiments and can include outcomes analysis or validation studies.
- Relevance for therapy development: Projects should aim to develop therapeutic agents that can be advanced towards development for neurological disorders. Projects should illustrate how the candidate therapeutic(s) will be optimized and advanced toward later stages of discovery once the R33 phase is complete. For example, plans for additional pharmacokinetic, formulation, and efficacy studies or focused optimization of the proposed early therapeutic (presented as a screening funnel) would be appropriate for certain types of therapeutics.
Examples of activities for the R61 phase include, but are not limited to:
- Preparation of the therapeutic agent(s) to support proposed activities.
- Characterization of therapeutic agent(s). This could include for example, confirmation of purity, stability, in vitro absorption, distribution, metabolism, and excretion, in vitro potency and selectivity, degradation products, and process impurities.
- Focused studies to optimize the candidate therapeutic agent(s) for in vivo efficacy testing
- Studies to develop dosage form(s) to support proposed PD measures and/or in vivo studies.
- Pharmacokinetics studies to determine direct or indirect therapeutic agent levels. For gene and cell therapy, these include characterization of gene copy numbers or tropism in tissues or cell engraftment.
- Studies to confirm that therapeutic agents reach and engage the target site (directly or indirectly) at a level that exceeds in vitro pharmacological potency over the desired period.
- Studies to inform design and refinement of the PD measure and/or in vivo efficacy models and testing procedures, including examination of model variability to estimate sample size, calibration of the model according to positive and negative controls, along with the age, time course and window of disease that are relevant for therapeutic testing.
At the end of the R61 phase, investigators must exhibit successful completion of 1) all necessary preparation and characterization (e.g., chemical synthesis and scale up to provide material for proposed project, in vitro or in vivo potency studies, in vitro organ, tissue or cell culture systems) of proposed therapeutic agent(s), 2) pharmacokinetic studies - for gene and cell therapy, this can be the level of tropism by copy numbers and engraftment in various tissue or cells, 3) design, refinement, and validation of pharmacodynamic and/or in vivo efficacy animal studies using the appropriate positive and negative controls and demonstrating feasibility of conducting therapeutic agent testing, and 4) a further refined in vivo study design (e.g., in an animal model) that meets the NINDS RIGOR guidelines (Landis et. al. Nature 2012, 490:187-91; and NOT-NS-11-023 ) and will allow for correlation of dose, therapeutic agent exposure in the target tissue, and pharmacological effect (i.e., demonstration of dose response and exposure response), thereby addressing subsequent feasibility.
Examples of activities for R33 phase include, but are not limited to:
- Pharmacodynamic and/or in vivo efficacy studies with chemically and biologically characterized therapeutic agent(s) including positive and negative controls, as appropriate.
- Dose (exposure)-response activity with the intended route of administration.
- Studies correlating pharmacokinetic and pharmacodynamics measures (PK/PD)?.
- Validation and replication studies to confirm observed results.
Examples of activities that are not appropriate for this FOA include, but are not limited to:
- Development of de novo animal models and pharmacodynamics measures.
- Assay development/identification of novel therapeutic agents (PAR-18-762 ).
- GLP toxicology studies/Investigational New Drug (IND) enabling studies with optimized therapeutic agents.
- Discovery or development of devices, surgical procedures, diagnostics, or rehabilitation strategies.
- Discovery and development of risk, detection, diagnostic, prognostic, predictive, or prevention biomarkers, although use of existing biomarkers is appropriate.
- Studies of disease mechanism.
- Study or use of therapeutic agents to identify targets relevant to a disease.
- Manufacture of therapeutic agents for clinical trials.
- Clinical research and clinical trials.
Successful projects should result in candidate therapeutics that meet the entry criteria for the NINDS Cooperative Research to Enable or Advance Translational Enterprises for Biologics program (CREATE Bio) Optimization Track (PAR-17-456 /PAR-17-457 ) or the Blueprint Neurotherapeutics Network (BPN) (PAR-17-201 /PAR-17-205 ) and facilitate future therapeutic discovery and development for neurological disorders and stroke. Information on these programs can be found on the Division of Translational Research Website at https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research.
Developing therapeutics requires a multidisciplinary approach. Investigators should form collaborations with those knowledgeable in the therapeutic development process (such as those from biotechs or pharma) as well as those familiar with what the desired end product should look like (such as biostatisticians, technical experts and clinicians). Applicants should consider how they will identify and foster relationships with potential licensing and commercialization partners early in the therapy development process once an award is made. PDs/PIs are expected to work closely with their institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project.
This FOA utilizes specific milestones that support transition from the R61 phase to the R33 phase and a project timeline. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision making, and they 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. Specific Aims or a list of activities planned for each year are not considered milestones because they do not provide decision-making goals.
NINDS emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress.
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) 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).
Resubmission
Revision
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
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.
1. Eligible Applicants
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
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.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.3. Additional Information on Eligibility
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
- A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
- A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
- An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)
1. Requesting an Application Package
Buttons to access the online ASSIST system or to download application forms 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.2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement 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.For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
Other Attachments: Applications should include an Intellectual property (IP) strategy. 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 therapeutic agent(s). Applicants should describe any known constraints that could impede their therapeutic discovery and development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies 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 an agent(s) 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 therapeutic 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.
Research Strategy: Within the Research Strategy, applicants should describe both the R61 phase and the R33 phase, including the R61 transitional milestones and timeline. The Research Strategy section should include a background section that clearly outlines the biological and therapeutic rationale for the application, including: 1) a description of the relationship between the proposed therapeutic target and the disease of interest, 2) evidence for unmet medical need in the therapeutic disease area, 3) a brief description of any pertinent history for therapeutic development in the disease area, 4) evidence supporting the novelty of the therapeutic approach, and 5) a summary of the project status, including information regarding therapeutic agents to be tested in the current application. Description of the R61 phase should include a carefully designed plan for characterizing the proposed preliminary therapeutic agents from a physicochemical, biophysical, and biological perspective. Since the goal of the R61 phase is to ensure that the candidate therapeutic is optimized for in vivo efficacy or pharmacodynamic studies, the research strategy for the R61 phase should also address plans for optimization of formulation or pharmacokinetic characteristics, as necessary to provide useful in vivo or pharmacodynamic data. In addition, there should be a carefully developed set of milestones, which should allow Go/No Go decisions at the end of the R61 approach section. An important component of the R33 phase strategy should be a carefully developed rationale for the experimental design and a description of the data analysis strategy. Finally, an outline of how data obtained in the R33 phase will provide a path for optimization of the preliminary therapeutic agent should be included.
Innovation: Include headers titled R61 Phase Innovation and R33 Phase Innovationand address the innovation for the R61 and R33 phases in the appropriate sub-section.
Milestones: Transition from the R61 to the R33 phase is contingent upon the successful completion of one set of proposed milestones. 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. Specific aims or a list of activities are 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.
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 (e.g., optimization of protocols, generation and characterization of therapeutic agents, pharmacokinetics studies, in vivo animal model adaptation and validation with positive and negative controls) 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.
Rigorous Study Design and Supporting Data: An R61/R33 Phased Innovation Award application in translational research should have a strong biological rationale for the intended approach, supporting data from rigorously designed experiments, and proposed studies that exhibit methodological rigor. NINDS urges applicants to the program to consider the rationale for the chosen animal model(s) and endpoints, adequacy of controls, route and timing of therapeutic dosing, justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results. (See NOT-NS-11-023: Improving the Quality of NINDS-Supported Preclinical and Clinical Research through Rigorous Study Design and Transparent Reporting.)
Therapeutic Discovery Plan: Each application funded through this FOA should be in position, if successful, to pursue further NIH or other private funding for preclinical optimization and development of their therapeutic agents. Therefore, it is essential for R61/R33 applicants to include, within the Research Strategy, a description of how knowledge gained from this work will support future therapeutic discovery efforts.
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.
Letters of Support: 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.
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.
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.
3. Unique Entity Identifier and System for Award Management (SAM)
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.gov4. Submission Dates and Times
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.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.6. Funding Restrictions
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.
7. Other Submission Requirements and Information
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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.
Section V. Application Review Information
Important Update: See NOT-OD-18-228 for updated review language
for due dates on or after January 25, 2019.
1. Criteria
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.Is there a sufficiently developed plan for the assessment of therapeutic agent chemical, biophysical, and biological characterization within the proposed grant period? Does the proposed study make scientific sense and is it designed rigorously? Are the proposed in vivo efficacy study and/or pharmacodynamic measures relevant to the proposed clinical indication? Are the proposed experiments part of a well-thought out and clearly defined therapeutic discovery plan? Are the in vivo models and preclinical outcome measures to assess efficacy and/or PD optimal for the proposed clinical indication? Is the project feasible? Will the project, if successful, produce robust pharmacodynamic or in vivo efficacy results that can support future therapeutic development? Will it produce therapeutic agent(s) that meet the entry criteria for BPN or CREATE Bio optimization or other future development mechanisms?
Key entry criteria for BPN and CREATE Bio include: (1) clear and convincing demonstration of proof-of-concept (e.g., clear dose-response relationship); (2) one or more therapeutic leads from, which a candidate can potentially be derived; (3) suitable and available in vitro and in vivo assays proposed to optimize the leads.
Have the investigators considered the rigor of their experimental design? Does the proposed project use sufficient experimental and statistical rigor? For key experiments, does the application explain assumptions for power analysis, describe statistical analysis methods and criteria for data inclusion or exclusion, and detail the procedures of how blinding and randomization will be conducted? Are controls appropriate, and have efforts been made to demonstrate an acceptable level of variability, so that the feasibility of the proposed studies can be adequately assessed?
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?
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 there additional key experiments that need to have milestones designated?
Intellectual Property (IP) Strategy
Are the following addressed as appropriate and consistent with achieving the goals of the program: Does the application outline any known constraints that could impede the therapeutic from being developed (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed while achieving the goals of the program? Does the applicant outline the IP landscape of their biomarker assay or method of detection? If applicable, how strong is the applicant's IP portfolio/position (pertinent to the proposed project), and to what extent does the applicant have a reasonable strategy to protect its IP going forward? If the applicant has filed patents pertinent to the assay, do they provide details about those patents? If IP will be shared among co-investigators, does the applicant provide details about the plans for IP sharing?
2. Review and Selection Process
- 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.
- Will receive a written critique.
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates
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.
1. Award Notices
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 grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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.
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.
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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS.
Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
3. Reporting
When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)
Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]
GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267
Rebecca Roof, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Section VIII. Other Information
and Human Services (HHS)
