Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title
Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Assay Development and Neurotherapeutic Agent Identification (R61/R33 Clinical Trial Not Allowed)
Activity Code

R61/R33 Exploratory/Developmental  Phased Award

Announcement Type
Reissue of PAR-18-762
Related Notices

See Notices of Special Interest associated with this funding opportunity

None

Funding Opportunity Announcement (FOA) Number
PAR-21-124
Companion Funding Opportunity
PAR-21-122 , R61/ R33 Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II
PAR-21-123 , R61/ R33 Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II
Assistance Listing Number(s)
93.853, 93.213
Funding Opportunity Purpose

This funding opportunity announcement (FOA) encourages research grant applications to develop in vitro and/or ex vivo assays and conduct iterative screening efforts to identify and characterize potential therapeutic agents for neurological or neuromuscular disorders. This FOA is part of a suite of Innovation Grants to Nurture Initial Translational Efforts (IGNITE) to advance projects to the point where they can meet the entry criteria for the Blueprint Neurotherapeutics Network (BPN) or other translational programs.

Key Dates

Posted Date
March 12, 2021
Open Date (Earliest Submission Date)
May 17, 2021
Letter of Intent Due Date(s)

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 13, 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

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.

Expiration Date
February 21, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Research Objective
This funding opportunity announcement (FOA) is part of a suite of Innovation Grants to Nurture Initial Translational Efforts (IGNITE) to encourage the translation of research discoveries into new treatments for disorders that fall under the NINDS mission, or NCCIH area of interest, as described below.

This FOA is intended to support: 1) development of new in vitro and/or ex vivo assays, and 2) screening efforts to identify and characterize novel therapeutic agents for neurological or neuromuscular disorders. These activities include (but are not limited to) set up and optimization, standardization, and validation of measures of fundamental cellular/molecular events such as binding, bioactivity at the target, and activity downstream of the target relevant to neurological function. The proposed assays must have sufficient throughput for iterative screening of potential therapeutic agents such as small molecules and biologics. The initiative also includes design and preparation of a focused set of therapeutic agents, and characterization thereof. The use of state-of-the art technologies for manipulation, detection, and analysis is encouraged. It is expected that upon completion, investigators will have a well-validated assay and therapeutic candidate(s) that meet the entry criteria for the NIH Blueprint Neurotherapeutics Network (BPN) or other late stage translational programs. Projects that seek to identify novel therapeutics for underrepresented patient populations are also responsive for this FOA.

This funding opportunity is intended to support projects with a strong biological rationale including evidence to support the novelty of the assay and/or platform, the unmet need for the assay, and a discussion of the role the assay will play in the therapeutic discovery decision making process for the intended target, which is relevant for treatments of disorders that fall under the NINDS mission or NCCIH area of interest as described below.

Phased Award Mechanism and Transition to R33
This FOA uses the R61/R33 Phased Innovation Award mechanism. The R61 phase will support the initial development, refinement, and validation of in vitro and ex vivo assays (including high throughput formats). The R33 phase will support: 1) iterative screening of potential therapeutic agents, 2) characterization of promising therapeutic agents from the screen, and may also support 3) efforts to design, prepare, and further characterize additional agents related to initial hits using a focused medicinal chemistry approach. 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. 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. Section IV includes additional information regarding project milestones. 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.

Projects funded through this FOA may include targeted and/or phenotypic assays. Choice of starting compounds/biologic agents for iterative screening should be based on a cogent biological and chemical rationale.

Entry Criteria

  • Novelty: This FOA seeks to apply new knowledge around novel targets, mechanisms and pathways. Projects should aim to develop therapeutics that are significant improvements over existing therapeutics for neurological or neuromuscular disorders. Applications should also aim to develop assays that are significant improvements over existing screening methods and should provide evidence of the unmet need for the assay.
  • Biological rationale and preliminary data: Projects funded through this opportunity must have a strong biological rationale for the intended approach. Preliminary data should reflect rigorous, well-designed experiments (either from the literature, data from other sources, or, when available, from investigator-generated data). Examples of the most critical elements for a well-designed study are summarized on the NINDS website (https://www.ninds.nih.gov/Funding/grant_policy).
  • Relevance for therapy development: Projects should aim to develop novel therapeutic agents that can be advanced towards development for neurological or neuromuscular disorders. Applications should illustrate how the assays will be used to identify candidate therapeutics and should include a plan for identification of preliminary therapeutic agents.

Examples of activities for R61 phase include, but are not limited to:

  • Development and validation of assay(s) (including phenotypic assays) to support a succinct testing funnel, including for example, assays to measure specificity, potency, stability to protease and/or other metabolic enzymes, and cellular uptake.
  • Development of in vitro or ex vivo potency/efficacy assays designed to indicate the specific ability of an agent to achieve a desired biological effect, for example: structural changes that may impact product quality, stability and efficacy. For use and development of iPSC lines, please see NOT-NS-14-032.
  • Development of assays to evaluate cellular uptake, engagement, infection, aggregation, downstream functional measures in vitro or ex vivo, purity and specificity. Assays to measure DNA, RNA, and protein levels of either endogenous genes or delivered products, downstream in vitro or ex vivo functional read-outs, viral titer, viral particle load stability and specificity.
  • Development of assays to evaluate purity and identity of the therapeutic by surface markers or specific proteins, morphological measures, differentiation, functional measures in vitro or ex vivo, stability and immunogenicity.
  • Assay development and/or optimization for High-Throughput Screening (HTS).
  • A combination of assays may be developed to demonstrate relevant biological activity when a single assay may not provide adequate measurement of overall potency due to a complex mechanism of action or multiple activities of a preliminary therapeutic agent.

Examples of activities for the R33 phase include, but are not limited to:

  • HTS, comprising screening of large libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis.
  • Preparation and screening of select series of therapeutic agents using for example medicinal chemistry or biological processes.
  • Preparation of therapeutic agent(s) and confirmation of structure, sequence or biological characteristics
  • Development and selection of cell lines/vectors to produce bioactive agents with acceptable potency and stability, cellular uptake/engagement, or secondary in vitro functional assays.
  • Assessment of therapeutic agent’s properties using computational analysis and early physicochemical measurements, polar surface area, solubility, cell permeability and efflux.
  • Assessment of initial in vitro pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion (ADME).
  • Assessment of potential off target activities.
  • Optimization of therapeutic agent(s) for future in vivo testing.

The knowledge gained from these studies should meet the entry criteria for the Blueprint Neurotherapeutics Network (BPN) (Funding Opportunities), or other late stage programs, and facilitate future therapeutic discovery and development for neurological disorders and stroke.

Collaborations

Developing therapeutics requires a multidisciplinary approach. Investigators are encouraged to form collaborations with those familiar with successful drug/biologic development (such as those from industry) as well as those familiar with what the desired end product should look like (such as clinicians and biostatisticians). 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.

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.
 

NCCIH-specific interests

NCCIH is interested in supporting research geared toward development of robust, validated, analgesic assays suitable for medium to high throughput screening of natural product libraries through the NINDS IGNITE program. For the purposes of this PAR, natural products are defined as extracts, chromatographic fractions, or isolated secondary metabolites derived from herbal, botanical, marine, microbial, or animal sources. NCCIH is prioritizing analgesic targets relevant to musculoskeletal, neuropathic, and inflammatory pain conditions. NCCIH will not support applications related to chemotherapy or cancer related pain conditions.

Examples of activities for the R61 phase include, but are not limited to:

  • Development and validation of assay(s) (including phenotypic assays) to support a distinct testing funnel of natural products with promising analgesic activity.
  • Development of in vitro or ex vivo potency/efficacy assays designed to indicate the specific ability of a natural product to achieve a desired analgesic effect.
  • Development of assays to evaluate cellular uptake, target engagement, downstream functional measures in vitro or ex vivo, purity and specificity of analgesic natural product leads.
  • Development of assays to measure DNA, RNA, and protein levels of endogenous genes, downstream in vitro or ex vivo functional read-outs for analgesic natural products.
  • Development and optimization of analgesic assays for High-Throughput Screening (HTS) of natural products.
  • A combination of assays may be developed to demonstrate relevant biological activity when a single assay may not provide adequate measurement of overall potency due to a complex mechanism of action or multiple activities of a preliminary therapeutic agent.

Examples of activities for the R33 phase include, but are not limited to:

  • Screening of large natural product libraries for activity against analgesic targets via the use of automation, miniaturized assays and large-scale data analysis.
  • Preparation and screening in analgesic assays of select subsets of natural products using for example chromatographic fractionation.
  • Isolation and structure elucidation of active analgesic natural products.
  • Assessment of initial pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion (ADME) of promising analgesic natural products.
  • Assessment of potential off target activities (abuse liability, respiratory depression, etc.) of promising analgesic natural products.

Applications utilizing a natural products library must clearly identify the source and the size of the library to be screened. The library to be screened can be a publicly available or private library but must be limited to natural products only. The library may include crude extracts, chromatographic fractions, isolated compounds or combinations of these. One notable publicly available natural products library is managed by the National Cancer Institute (https://dtp.cancer.gov/organization/npb/introduction.htm). There is no minimum required size of the library, but applicants must articulate how the library will be suitable for screening and sufficient to identify promising analgesic leads. Furthermore, medicinal chemistry efforts of any identified analgesic compounds must be limited to efforts designed explicitly to elucidate mechanism of action of the compound (e.g. target pull down, click chemistry, etc.).

For Both NINDS and NCCIH:

Applications Not Responsive to this FOA

Non-responsive studies include those that involve any of the following activities:

  • Applications focused on indications outside the mission of NINDS that do not meet NCCIH’s above stated interests for screening natural products for non-cancer pain.
  • Studies designed to establish proof of concept for a biological target.
  • Applications with the primary focus of developing pharmacodynamic biomarkers (covered by PAR-19-315)
  • Development of assays or probes to support basic understanding of disease or other basic research.
  • In vivo efficacy studies (covered through companion PAR-21-122)
  • Development of devices (covered by this program: https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Translational-Research/Funding-Programs-Researchers/Translational-Devices), device/drug combinations, surgical procedures, diagnostics, and rehabilitation strategies.
  • Development of risk, detection, diagnostic, prognostic, predictive, and prevention biomarkers.
  • Studies of disease mechanism.
  • Studies or use of therapeutic agents to identify targets relevant to a disease.
  • Investigational New Drug (IND) enabling studies.
  • Manufacture of therapeutic agents for clinical use.
  • Development of bioassays for clinical use.
  • Human subjects research, with the exception of studies falling under 45 CFR 46.101(b) (4) (Exemption 4) https://grants.nih.gov/sites/default/files/exemption_infographic_v8_508c_1-15-2020.pdf. According to 45 CFR 46, a human subject is "a living individual about whom an investigator (whether professional or student) conducting research:
    • Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
    • Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens."

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.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission
Revision

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.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Direct costs cannot exceed $499,000 in any one year. Cumulative direct costs for the entire three-year project period may not exceed $750,000.

Award Project Period

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or 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 Other Than Institutions of Higher Education

  • 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)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • 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)

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • 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)
Foreign Institutions

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. 

Required Registrations

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.

  • 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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

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:

  • 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).

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

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.
Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

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 therapy and assay. 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 therapy 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.

SF424(R&R) Senior/Key Person Profile

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.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research 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, including the technical questions you will try to answer to determine the feasibility of the proposed approach. Since the goal of the R61 phase of this FOA is the development and validation of assays, hypothesis testing, per se, may not be the driving force in developing such an application, and therefore, may not be applicable in the R61 phase.

Research Strategy: Applications funded through this opportunity should provide a strong biological rationale, which includes evidence to support the novelty and/or unmet medical need for the therapeutic target or therapeutic approach. In addition, the rationale should provide evidence supporting the novelty of the assay, the unmet need for the assay and a discussion of the role the assay will play in the therapeutic discovery decision-making process for the intended therapeutic target (therapeutic discovery plan). Supporting information, which addresses the biological rationale and the unmet need for the assays to be developed, is required. The applicant should discuss the strengths and weaknesses of the prior research used to support the application and describe how the proposed research will address weaknesses or gaps identified by the applicant. This may include the applicant’s own preliminary data, data published by the applicant, or data published by others. The NIH expects this consideration to include attention to the rigor of the previous experimental designs, as well as relevant biological variables and authentication of key resources. Applications should also address the methods and rationale for an assay validation plan in a thorough and carefully thought-out manner. Assay validation is a process that determines the fitness of an assay, which has been properly developed, optimized and standardized, for an intended purpose. Assay validation should be clearly outlined to cover critical topics such as but not limited to i) definition of the intended purpose(s), ii) optimization, iii) standardization, iv) reproducibility, v) sensitivity, vi) specificity, and vii) thresholds (cut-offs). In order to assess the predictive value of preclinical research, sufficient information should be available about study design, execution, analysis, and interpretation. Finally, applicants should clearly outline a therapeutic discovery plan, which would include the role their assay(s) would play in the identification of early therapeutic candidates and how these findings impact translational research priorities of the NINDS or NCCIH as outlined above. An outline of how data obtained in the R33 phase will provide a path for optimization of preliminary therapeutic agents is also appropriate.

Within the Research Strategy, applicants must describe both the R61 phase and the R33 phase, including the milestones at the R61/R33 transition point, and timeline. Applicants should clearly outline the rationale for choosing the proposed studies, the choice of therapeutic agent(s), target or pathway, and how it fits within the therapeutic discovery plan. The research strategy for the R61 phase should address the validation status of proposed assays. The application should describe how the assays developed in the R61 phase will be implemented in the R33 phase, and how decisions about which compounds to test in each iteration will be made. As this is an R61/R33 mechanism, both phases must be requested and planned (the two phases should not overlap in time). Applications proposing only one phase will be administratively withdrawn without review.

Innovation: Include headers titled R61 Phase Innovation and R33 Phase Innovation and address the innovation for the R61 and R33 phases in the appropriate sub-section. Novelty of therapeutic strategy/target over what’s currently available in the clinic or under therapeutic development should be emphasized. A description of the therapeutic strategy in relation to the state of the field should be included.

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 and successful completion of the R61 phase. In addition, milestones should reflect the objectives of the application and be appropriate for the therapeutic approach and indication. Rationale should be provided for the choice of measures and values proposed for the milestones. 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(s). The existence of clear, quantitative, go/no-go milestones for transition from the R61 to the R33 phase are 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 (e.g., set up and validation of assay) 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. (See NOT-NS-11-023: Improving the Quality of NINDS-Supported Preclinical and Clinical Research through Rigorous Study Design and Transparent Reporting.) Applicants should consider the rationale for the chosen assay, the conditions for the assay, and the selection of the therapeutic agents to be tested. All studies should focus on critical issues such as development of appropriate controls (e.g., reference standard(s)), sample management, bioinformatics, data analysis, demonstration of dynamic detection range, robustness, portability, stability and variability. Special consideration should be taken to ensure that assays address critical attributes such as robust signal change to enable detection of activity compared to background noise within the assay (Z score determination), kinetic parameters to ensure that the assay is functioning correctly, and stability to allow feasible numbers of compounds to be tested within a set timeframe. Provide evidence that controls are appropriate and that control efforts have been taken to demonstrate a sufficient dynamic range and acceptable variability, so that the feasibility and utility of conducting the proposed assays can be adequately assessed.

Therapeutic Discovery Plan: At the completion of this project, it is expected that applicants have an assay and promising small molecule or biologic starting point for the BPN, other later-stage NIH program or private investment. Applicants are encouraged to review the BPN entry criteria and associated funding opportunities. More details can be found at Blueprint Neurotherapeutics Network (BPN). It is essential for applicants to include, within the Research Strategy, a description of how knowledge gained from this work will support future therapeutic discovery efforts beyond the project period through to early clinical trials. As part of this consideration, attention should be paid to the intended patient population such that appropriate experiments (assays, targets, etc.) are used in the current application.

Collaboration: NINDS strongly encourages applicants to form multidisciplinary teams that consist of academic/industry experts relevant to the research plan (i.e., biostatisticians, clinicians, drug development experts, 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 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.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

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.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign Institutions

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.gov.

4. 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 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.

 

 

 

Post Submission Materials

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.

Section V. Application Review Information

1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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.

Significance

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?

Will the project, if successful, bring the investigators closer to a therapeutic that will be a marked improvement over existing therapeutics to treat neurological disorders? Are the starting compounds/biologics chosen based on sound scientific rationale? Does the application show an understanding of the state of the field and where the proposed therapeutic approach fits within the therapeutic landscape?

Investigator(s)

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?

Are the investigators knowledgeable and experienced about the biological target area? Have researchers with preclinical expertise, necessary statistical expertise, and experts in relevant therapy modality development been included in the conception, design, and proposed implementation of the project? Does the team have sufficient expertise to not only perform the experiments purposed, but anticipate and mitigate issues that might arise in the 3-year IGNITE project and set the project up for success beyond IGNITE? Have they formed multi-disciplinary collaborations?

Innovation

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 there clear, well-defined goals to pursue novel targets, mechanisms and pathways? Does the application make a compelling case that the strategy proposed is distinct from other therapeutic approaches and has a reasonable chance of success considering the landscape?

Approach

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?

Is the project feasible? Will the project, if successful, produce a well-validated assay that can support future therapeutic development for neurological disorders? Is the process for selecting compounds/biologics at each iteration appropriate? Is the plan for therapeutic candidate discovery reasonable? Will it produce therapeutic agents that meet the entry criteria for BPN or other further development mechanisms? Key entry criteria for BPN include:

  1. Rigorous data supporting the hypothesis that modulating the putative drug target/affected pathway will produce a desirable outcome for the intended disease indication

  2. One or more characterized bioactive 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.

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 dynamic detection range and acceptable variability, so that the feasibility of the proposed studies can be adequately assessed?

Is the timeline reasonable for the work proposed?

Environment

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?

Additional Review Criteria

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 a 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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Additional Review Considerations

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

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? 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?

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • 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.

Section VI. Award Administration Information

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 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.

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, 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Becky Roof, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: rebecca.roof@nih.gov


Craig Hopp, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-496-5825
Email: hoppdc@nih.gov

Shelley Carow
National Center For Complementary & Integrative Health (NCCIH)
Phone: 301.594.3788
E-mail: carows@mail.nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.


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