National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
R35 Outstanding Investigator Award
- July 18, 2024 - Notice to Allow Requests for Budget Increases for NINDS Research Program Award (R35). See Notice NOT-NS-24-124
- NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
- September 14, 2022 - Notice of Change to Eligibility Information for RFA-NS-22-038. See Notice NOT-NS-23-025.
- September 12, 2022 - Notice of Change to Eligibility Information for RFA-NS-22-038. See Notice NOT-NS-23-023.
- NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
The purpose of the NINDS Research Program Award (RPA) is to provide longer-term support, and increased freedom and flexibility to Program Directors (PDs)/Principal Investigators (PIs), to allow them to redirect their time away from the administrative burden of writing and managing multiple grant applications and towards engaging in the lab. This RPA affords investigators at most career stages the opportunity to advance their long-term research goals, rigorously explore exciting research opportunities, and mentor students and postdoctorates, which support and align with the mission of NINDS. RPAs will support the overall research programs of NINDS-funded investigators for up to 8 years, at a level commensurate with a PD/PI’s recent NINDS support (Part 2, Section II). This greater funding stability will provide eligible investigators increased security, allowing them to undertake research projects that require a longer timeframe or to embark upon research that breaks new ground. Research activities outside of the NINDS mission, or traditionally supported by another NIH Institute or Center, will not be considered through this program.
Benefits of the RPA include:
- A more stable funding environment, facilitating the pursuit of longer-term research goals;
- Flexible funding, enabling investigators to pursue research opportunities as they arise, not tied to specific aims;
- Reduced time spent writing grant applications and managing multiple grant awards, allowing investigators to spend more time conducting and overseeing research;
- More time for PDs/PIs to mentor and foster a diverse workforce in their laboratories.
The RPA is a unique program for NINDS, as such NINDS strives to ensure it reflects our commitment to enhancing the diversity and inclusiveness of the neuroscience workforce. A diverse NIH-supported scientific workforce, including individuals from underrepresented groups, fosters scientific innovation, enhances global competitiveness, contributes to robust learning environments, and improves the quality of the research (see NIH’s Interest in Diversity).
NINDS will work to ensure that it maintains a broad and diverse research portfolio in terms of scientific areas, approaches, regions, institutions, and individuals. Such diversity will optimize returns on the Institute’s investments by maximizing the ideas explored and the chances for important breakthroughs.
Note that, while this funding opportunity also accepts clinical trials, only applications proposing mechanistic clinical trials or studies or basic experimental studies with humans (BESH) will be accepted. For information on the types of clinical trial that are within scope of this funding opportunity announcement, refer to Funding Opportunity Description, below.
30 days prior to application due date.
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| July 13, 2022 | Not Applicable | Not Applicable | November 2022 | January 2023 | April 2023 |
| July 13, 2023 | Not Applicable | Not Applicable | November 2023 | January 2024 | April 2024 |
| July 15, 2024 | Not Applicable | Not Applicable | November 2024 | January 2025 | April 2025 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the 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.
Overview:
The majority of grant awards are limited to 2-5 years and support individual projects, rather than the overall research program of an investigator's laboratory or research group. PD/PIs spend a considerable portion of their time writing grant applications rather than performing and overseeing research and directly mentoring individuals in their laboratories. The NINDS RPA aims to support the NINDS-related research of an investigator's laboratory or research group for a sustained period. The award is intended to increase funding stability, reduce the time investigators spend writing grant applications, and facilitate a more flexible research environment. This should allow for increased time for investigators to be directly involved in the research in their laboratories, fostering more creative and/or long-term research goals, enabling more engagement with students and postdoctorates, and assuring a high level of rigor and attention to experimental design all of which contribute to advancing the mission of NINDS.
Because the RPA is intended to support most, if not all, of the NINDS-related research in an investigator's laboratory, investigators receiving an RPA must relinquish their other NINDS research grants, with a limited number of exceptions, see below. PD/PIs can retain non-overlapping grant support from other NIH ICs, provided they maintain the required level of effort on the RPA (see below). The grant awards that PDs/PIs receive from leading or participating in NINDS multiple-PD/PI research grants, program project grants, and/or Center grants will also be incorporated into the RPA, but the investigator will be expected to continue the collaboration with support from the RPA.
By replacing all or most of an investigator's NINDS funding, the RPA should support research that is the major focus of the investigator’s laboratory or research group. Therefore, the PD/PI must devote at least 6 person months (i.e., the equivalent of 50% effort on a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment) to the RPA throughout the duration of the award. Applications from PD/PIs committing less than the required amount will not be accepted. When applicable, PDs/PIs will be expected to renegotiate their time and effort on other non-NINDS awards to accommodate the level of effort required by the RPA.
The budget for the RPA will be set at a fixed level that is generally commensurate with the PD/PIs funding over the prior four years. No RPA budget will exceed $750K direct costs (DC) per year, and no RPA will be awarded for less than $350K direct cost (DC) per year. Applicants should refer to Section II, Award Budget for guidance on preparing their budget, and NINDS R35 FAQs (e.g., How should I determine my RPA budget? Could you provide a template for calculating and providing my budget?) for examples. When considering an RPA application, investigators should balance this funding paradigm against the benefits of the RPA, which include:
- Funding stability for up to eight years, contingent upon National Advisory Neurological Disorders and Stroke (NANDS) Council approval of scientific progress during the first five years
- Support for an investigator's currently-funded NINDS research grants will in effect be extended through the RPA, without requiring submission of separate renewal applications;
- Reduced administrative burden and relief from the constant pressure to write multiple grant applications and manage multiple grant awards.
- Increased flexibility to pursue new ideas and scientific opportunities as they arise since the award does not require specific aims and is not predicated on completing specific, pre-defined research objectives.
The goal of the RPA mechanism is not to expand an investigator's current level of NINDS funding. However, NINDS acknowledges that there are circumstances where a flat budget may limit the ability of productive research programs, particularly for those investigators with limited external sources of funding, to capitalize on new and emerging scientific opportunities. Furthermore, NINDS recognizes that the research programs of investigators earlier in their career may require additional funding as their programs mature. Therefore, NINDS offers supplemental funding for PDs/PIs to request budget increases along with their year -06 RPPR via an administrative supplement.
- As part of the consolidation of an investigator’s NINDS research into the RPA, institutions will be required to relinquish their financial interests in current NINDS-funded research grants where the applicant investigator is listed as a PD/PI (e.g., research project grants (RPGs), P01s, P50 and other Center awards [including leads on subprojects/project leaders]).
Grants not subject to consolidation into the RPA:
The following grants are not subject to consolidation into the RPA. An RPA recipient can retain and also remain eligible to apply for these types of activities:
- Grants or cooperative agreements submitted in response to FOAs exclusively supported using Congressionally directed set-aside funds. At this time, these are limited to the Brain Research through Advancing Innovative Neurotechnologies (BRAIN ) Initiative, the Helping to End Addiction Long-term (HEAL) Initiative, the Countermeasures Against Chemical Threats (CounterACT) program, and the Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) program.
- Grants or cooperative agreements submitted in response to the NINDS IGNITE, CREATE, or Translational Neural Devices Programs or the Blueprint Neurotherapeutics Network;
- Grants or cooperative agreements supporting clinical trials submitted in response to NINDS clinical trials FOAs;
- Grants or cooperative agreements that exclusively support research resources (e.g., P30, R24 or U24 awards);
- Grants or cooperative agreements supporting training, diversity, or workforce development;
- SBIR/STTR grants or cooperative agreements;
- Conference grants or cooperative agreements;
- Contracts
In addition to those listed above, the PD/PI will remain eligible to apply for some additional sources of NINDS funding, including administrative supplements. However, applicants should contact NINDS with questions or for further clarification regarding excepted programs.
RPA awardees are encouraged to continue existing collaborations on NINDS grants as part of multi-PD/PI project teams. However, support for these or future collaborative activities will come from the RPA. Given, RPA investigators will be permitted to accept a limited amount of support from other NINDS-funded investigators as a co-investigator or consultant, the level of support should not significantly exceed the level of subcontracted support at the time the RPA is made. Awardees are strongly encouraged to contact NINDS staff prior to agreeing to participate in activities not funded by the RPA.
To mitigate against a lapse in funding, a PD/PI may submit an NINDS application of scientifically overlapping scope in parallel with the RPA application with the understanding that if both applications are judged to be meritorious and considered for funding, only one of the awards could be accepted.
Duration:
The award period will be for 8 years contingent upon administrative review of RPRR submitted materials and NANDS Council approval prior to the year -06 start date. An administrative supplement request for a budget increase for years 6-8 may also be submitted at this time, with a one paragraph budget justification in the year -06 RPRR. This review will assess whether the investigator's research program is progressing appropriately. In this review, NINDS staff and the NANDS Council understand that the RPA is intended to support projects that may involve higher risk and longer-term research. NINDS anticipates that most RPAs will be extended. If the administrative review of the year-06 RPRR submitted materials determines that a research program is not progressing adequately, the investigator will be encouraged to apply for other competitive research project funding from the NIH and the level of RPA funding will be reduced. If the investigator chooses to accept another NINDS grant award, he/she will be required to relinquish the remaining time and funds from the RPA.
Eligibility:
Eligibility to apply through this FOA is limited to individuals who have been funded continuously as PD/PI in each of the past five consecutive years at the time of application submission. Funding must include one of the following types of active NINDS grants in each of the past 5 years with no more than one of those years in a first no cost extension: R00, R01, R35, R37, R56, DP1, DP2. Applications with more than one NCE will be considered under exceptional circumstances (e.g., research progress or lab time affected by the COVID-19 pandemic or other emergency situations).
The RPA is intended to provide more stable funding to PDs/PIs across career stages and from a wide range of diverse backgrounds who have demonstrated productive, rigorous track records which support and align with the mission of NINDS
Accomplished PDs/PIs who have made significant scientific contributions after one cycle of grant support are particularly encouraged to apply. NINDS will seek to ensure that RPA awards are diverse with respect to scientific approach, area of study, perspectives within the PDs/PIs laboratory and career stage. NINDS strongly encourages women and individuals from diverse backgrounds (including nationally underrepresented groups) to apply.
For Current NINDS R35 Grantees
- To prevent a lapse in funding, current NINDS R35 grantees can submit a new NINDS Type 1 R35 application in years 7-8 of their active R35 award. Please note that Type II Competing Continuation applications are not permitted in the R35 program. Additionally, PD/PIs can submit other overlapping applications (e.g., R01s) during this period. However, if all applications receive fundable scores, PD/PIs will have to choose between either the new R35 or one or more of the other nonR35 NINDS awards.
- If the PD/PI of an active NINDS R35 award submits a new NINDS Type 1 R35 application prior to the 7th year of their active R35 and receives a fundable score, the remaining time and funds from the active NINDS R35 must be relinquished if the PD/PI chooses to accept the new award.
Clinical Trials:
For clinical trials, only applications proposing mechanistic clinical trials or studies or basic experimental studies with humans (BESH) will be accepted. Note the following definitions for this funding announcement:
- Mechanistic trials, defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention.
- Basic Experimental Studies with Humans (BESH), defined as basic research studies involving humans that seek to understand the fundamental aspects of phenomena.
- A Clinical Trial Synopsis (6 pages maximum) should be included. See Section IV. Application and Submission Information for details to be included in the Clinical Trial Synopsis
The following research will not be supported through an NINDS RPA and applications that feature this research will be considered non-responsive, and will not be reviewed:
- Research outside of the NINDS mission, or traditionally supported by another NIH Institute or Center;
- Activities supported by another NIH Institute or Center, federal or state agency, or private foundation;
- Clinical trials that seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions, preventive, therapeutic, and services interventions will not be supported by NINDS under this FOA. Please refer to https://www.ninds.nih.gov/Funding/Find-Funding-Opportunities to find the appropriate NIH or NINDS-specific FOA for such clinical trials.
- For further clarification on how NIH defines the different types of clinical trials, please refer to the following resources.
PDs/PIs are encouraged to review the Frequently Asked Questions and/or contact NINDS' Program/Research staff prior to submission of an RPA application to discuss whether their application is relevant to the NINDS mission and does not overlap with grants from other NIH ICs or independent funding entities.
As appropriate, applicants are encouraged to make use of the following NIH resources for clinical research including:
-
- Clinical and Translational Science Award (CTSA) program (https://ctsacentral.org/);
- NeuroQOL (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol);
- NIH Toolbox (http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox);
- PROMIS (http://www.healthmeasures.net/explore-measurement-systems/promis); and
- NINDS Common Data Elements (https://www.commondataelements.ninds.nih.gov/#page=Default
Rigor:
NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/Funding/grant_policy).
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Optional: Accepting applications that either propose or do not propose clinical trial(s).
NINDS intends to commit up to $20 million per fiscal year and up to 25 new awards per year, for the duration of this RFA . NINDS will seek to ensure that RPA awards are diverse with respect to scientific approach, area of study, perspectives within the PDs/PIs laboratory and career stage.
Applicants may request up to a maximum of $750,000 direct costs (DC) per year; however, the requested RPA budget must be commensurate with the investigator's recent level of NINDS support. That level of support must be calculated using the average direct cost for 4 consecutive out of the 5 most recent years. You can use NIH RePORTERto find your NINDS awards. Calculations should use awarded direct costs (including administrative cuts), and in the case of MPD/MPI awards or multi-component grants/cooperative agreements, should only include the amount of the total award that is attributable to the applicant PD/PI. Moreover, in the case of multi-component grants/cooperative agreements, the budget should not incorporate funds attributable to cores, as these funds will not be folded into the RPA. Please note that pending support should not be considered when developing an RPA budget, even if such applications should get funded between the R35 submission and award. Although the RPA mechanism is not intended to support the expansion of an investigator's current level of NINDS funding, RPAs will be awarded for no less than $350K DC. Barring this exception, only in rare and extremely well-justified circumstances (e.g. an investigator is still within the growth phase of their careers) will awards exceed the most recent 4-year funded average of NINDS grants subject to be folded in. Applications submitted with budgets of more than 20% over the 4-year average described above will be considered non-compliant to this FOA and will be withdrawn prior to review PDs/PIs may reach out to discuss their proposed budgets / projects with NINDS program staff [prior to submission.] PDs/PIs should provide detailed evidence supporting their budget request in the budget justification section along with a table demonstrating their average funding in each fiscal year (e.g., FY18, FY19, FY20, FY21, FY22) with the associated grant number and awarded direct cost in each of those NIH fiscal years. Fiscal year award information for an investigator’s grants can be found on NIH’s RePORTER and budget examples can be found here https://www.ninds.nih.gov/Funding/About-Funding/Research-Program-Award-R35). Year one of the R35 award will be offset by any funds disbursed in the same FY from awards that will be folded into the RPA.
Applicants should request a project period of 8 years
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the 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.
- 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.
- 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.
- Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
- Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.
- eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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.
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.
Eligibility to apply to this FOA is limited to PDs/PIs who meet all the following criteria:
- PDs/PIs who have had at least one of the following types of active NINDS grants in each of the past 5 years (e.g., FY18-22; FY19-23; FY20-24), R00, R01, R35, R37, R56, DP1, DP2. Potential applicants are encouraged to refer to NINDS R35 FAQs to check eligibility. Applications with more than one NCE will be considered under exceptional circumstances with a 1 sentence description in the budget justification of the reason for multiple NCEs.
- PDs/PIs whose 4-year NINDS funding history is limited to a single MPI or multi-component grant are not eligible to apply.
The research supported by an RPA should be the major focus of the investigator’s laboratory or research group. Therefore, the PD/PI must devote at least 6 person months (i.e., the equivalent of 50% effort on a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment) to the RPA throughout the duration of the award period.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).
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.Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
Alisa Schaefer, Ph.D.
E-mail: [email protected]
Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Instructions for Application Submission
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
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.
Clinical trial synopsis (6 pages maximum): Applications proposing a mechanistic or BESH trial, must provide a concise summary of the clinical trial protocol including the items listed below. Information that is required as part of the PHS Human Subjects and Clinical Trials Information Form need not be described in detail in this section; specific details can be referenced to the attached full protocol or the PHS Human Subjects and Clinical Trials Information Form. NINDS expects that the full protocol included in the application should support this concise summary.
Include a summary of the following:
- A description and rationale for the selected study design
- Rationale for selecting the study population (as described in section 2 of the Human Subjects form) and why it is an appropriate group to answer the question under study
- Rationale for selection of the intervention(s) to be tested and study outcomes and endpoints (for clinical trials)
- A list of subject inclusion/exclusion criteria, or of group eligibility criteria (for group-randomized trials)
- A description of all assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions.
- A discussion of potential biases and/or challenges in the protocol and how they will be addressed
- A discussion of how the study investigators will be kept blinded to treatment group-specific data during the course of the clinical trial, if applicable.
Bibliography: Each application must include a PD/PI publication list (Bibliography) from the past five years, under Other Attachments . In this section, applicants should include: 1) a listing of publications (separating out research articles from review articles and commentaries) to document the PD/PI’s research trajectory, 2) provide up to a half page description highlighting the rigor in these publications, and 3) address any papers that were retracted.
Mentoring, Service, and Inclusion (3 page maximum): NINDS places significant value on high-quality mentorship and inclusive training environments. NINDS has described some of the characteristics that define outstanding mentorship and strategies for diversity and inclusion. In this section, applicants must include a document under Other Attachments providing: 1) A description of their commitment and dedication to mentorship and training in neuroscience research (e.g., Landis award), 2) A description of ongoing and planned outreach and mentoring activities, to enhance workforce diversity in the applicant’s laboratory NOT-OD-20-031. 3) A description of planned activities during the grant period designed to develop or enhance skills of talented scientists from a wide variety of demographic groups, including individuals from underrepresented groups, and any actions planned to promote inclusive and equitable scientific biomedical research environments, and 4) A description of significant contributions of service to the research community (e.g. study section service).
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
Biographical Sketch:
A biosketch should only be provided for the PD/PI and in rare cases, for co-investigators receiving financial support from the RPA.
The RPA is intended for investigators at most career stages with track records of research achievement and productivity commensurate with career stage and taking into consideration significant life events (e.g., childbirth, family care, serious illness or disability, military service). NINDS strongly encourages women and individuals from underrepresented groups (as described in the Notice of NIH’s Interest in Diversity) to apply.
The PD/PI should address these considerations within the Biosketch.
Current & Pending Support:
This attachment is required. For the PD/PI only, use the SF424 R&R Current and Pending Support instructions as modified here. To minimize redundancy, grants and other support reported in the Current and Pending Support section can be simply listed by grant numbers or other relevant identifiers (for other types of support). Do not list Total Costs for the Entire Project Period; instead list Annual Direct Costs allocated to the R35 PD's/PI's laboratory, only. List the PD's/PI's effort on each support mechanism in person-months.
All sources of support including foreign support should be reported. List NINDS grants first, followed by other NIH grants, followed by other sources of support.
Include all current NIH fiscal year and pending NIH fiscal year support (including subcontracted support) for the PD/PI (even if they receive no salary support from the project(s)) for ongoing projects and pending applications.
.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
While a 10-year R&R Detailed Budget form is provided in the application package, applicants need to request 8 years of support. Unallowable costs will not be considered. PDs/PIs should provide in the budget justification, detailed evidence supporting their proposed request (e.g. table calculating 4-year average of direct costs, including grant numbers with awarded direct costs for each year; for example see https://www.ninds.nih.gov/Funding/About-Funding/Research-Program-Award-R35. Calculations should use awarded direct costs (including administrative cuts), and in the case of MPI/MPD awards or multi-component grants/cooperative agreements, should only include the amount of the total award that is attributable to the applicant PD/PI. Moreover, in the case of multi-component grants/cooperative agreements, the budget should not incorporate funds attributable to cores, as these funds will not be folded into the RPA. Applicants must commit at least 6 person months (i.e., the equivalent of 50% effort on for a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment) throughout the duration of the RPA period. Applications from PD/PIs committing less than 6 person months for the duration of the award will not be accepted.
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
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims:
Specific Aims should not be submitted.
Research Strategy:
Upload the Research Strategy as a single attachment containing the following information. Material covered in the Biosketch should not be repeated.
1) Background regarding the area(s) of research proposed and key gaps in our understanding or challenges that need to be addressed. Describe the scientific question (s) that you will address and their importance.
2) Description of:
- Your recent research advances
- How the increased stability of this mechanism will allow for continued innovation in the field, and potential to move the field forward
- Progress during the previous five years providing examples of your conduct of rigorous research and transparent reporting.
- How you will leverage your recent contributions (e.g., novel ideas, accomplishments, experience, sustained productivity, etc.) into the new approaches proposed in your research program.
- How you will continue to generate important scientific advances throughout the proposed research program.
- How the RPA mechanism will allow your program to continue to grow
- How the proposed research program addresses a problem that is sufficiently comprehensive and substantial to be appropriate for long-term pursuit
- How you will advance the scientific and technical merit of the proposed project through expanded inclusivity. The description should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application.
3) Overview of proposed research program. Describe the overall vision, conceptual framework and planned strategies for advancing and sustaining the proposed research program for the next eight years. Identify the key questions or challenges you plan to address and approaches and tools that might be used to address them. Discuss the importance of the research question, and how the research would affect current understanding of the problem being addressed and/or advance the field of study. As appropriate, include plans for transparent reporting, resource/data sharing and consideration of sex and other biological variables in the research program.
The proposed research can be either a continuation of your previous or current work or involve a new line of investigation. If the planned research program diverges significantly from your past/current work, explain your rationale for the changes and describe your ability to undertake this new direction. A detailed experimental plan is not expected, nor is preliminary data required. Figures can be used sparingly to highlight critical pieces of data and/or to provide a high-level summary of the overall research program. Although the proposed direction of the research program will be considered in review, if new opportunities or directions arise during the course of the research, you will have the flexibility to change course and pursue them, as long as they remain within NINDS mission that will be assessed at the five-year administrative review. Whether the program is an extension of current work or a new line of investigation, describe how the flexibility, level of effort, and longer-term funding offered by the RPA would increase the potential for more impactful scientific outcomes than through current or future R01 level grant funding.
4) If proposing a clinical trial (mechanistic trial or BESH), concisely state the need, rationale, timeliness, scientific relevance, and potential impact of the proposed study and include a Clinical Trial Synopsis (maximum 6 pages) with pertinent details as stipulated in Section IV. Application and Submission Information
Rigor of Research Strategy:
NINDS urges investigators to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described at https://www.ninds.nih.gov/Funding/grant_policy. This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These recommended research practices include, where applicable, expressing clear rationale for the chosen model(s) and primary/secondary endpoint(s), describing tools and parameters clearly, blinding, randomizing, ensuring adequate sample size, pre-specifying inclusion/exclusion criteria, appropriately handling missing data and outliers, implementing appropriate controls, preplanning analyses, and using appropriate quantitative techniques. It is also strongly recommended to indicate clearly the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications.
Investigators should indicate whether data presented or cited in the application as key support for the proposed work were collected, analyzed, and reported in a rigorous and transparent manner as indicated above. A plan to address any ambiguity, weaknesses, or limitations in the prior research should be included in the application. Proposed experiments should similarly adhere to these high standards of rigor and transparency.
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, are expected to address a Data Sharing Plan.
Letters of Support:
The application must include a letter from the institution's Authorized Organizational Official (AOR) indicating that they are aware of and accept the condition that other NINDS research awards must be relinquished as a condition of receiving a RPA (as described in Part 2, Section I), and providing a statement that if chosen to receive an award, the PD/PI must devote at least 6 person months (i.e., the equivalent of 50% effort on for a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment) to the RPA throughout the duration of the award period.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
- No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
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.
For any delayed onset mechanistic or BESH clinical trials, prior approval from NINDS program staff is required before initiating the trial. At the time of request for approval, and at least 6 months prior to the start of the delayed onset mechanistic or BESH clinical trial, the PD/PI should submit to NINDS program staff a Clinical Trial Synopsis.
Clinical Trial Synopsis (6 pages maximum): If proposing a new mechanistic or BESH clinical trial, provide a concise summary of the clinical trial protocol including the items listed below. Information that is required as part of the PHS Human Subjects and Clinical Trials Information Form need not be described in detail in this section; specific details can be referenced to the attached full protocol or the PHS Human Subjects and Clinical Trials Information Form. NINDS expects that the full protocol included in the application should support this concise summary.
The Clinical trial synopsis should include the following:
- A description and rationale for the selected study design.
- Rationale for selecting the study population (as described in section 2 of the Human Subjects form) and why it is an appropriate group to answer the question under study.
- Rationale for selection of the intervention(s) to be tested and study outcomes and endpoints (for clinical trials).
- A list of subject inclusion/exclusion criteria, or of group eligibility criteria (for group-randomized trials).
- A description of all assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions.
- A discussion of potential biases and/or challenges in the protocol and how they will be addressed.
- A discussion of how the study investigators will be kept blinded to treatment group-specific data during the course of the clinical trial, if applicable.
PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
It is anticipated that the terms of award will include, but not be limited to, the following:
A permanent change of PD/PI will not be allowed under the RPA. A temporary change may be allowed with prior approval under circumstances such as sabbatical leave, medical conditions, disability, or personal or family situations.
Transfer of an RPA to a foreign institution will not be allowed. Addition of a foreign component, including a significant new foreign collaboration requires prior approval.
It is expected that the RPA will replace current NINDS funding of the laboratory. Institutions will be required to relinquish their interests in current NINDS-funded research grants where the applicant investigator is listed as the PD/PI or project lead on e.g. research project grants (RPGs), P01s, P50 and other Center awards [including Leads on subprojects] or proportional interest in awards where the applicant is one of a multiple PI team (MPI), with the exceptions of those indicated in Part 2, Section I of this FOA. The initial budget period of the RPA and timing of the award will be negotiated so that a smooth transition of support takes place.
It is expected that the PD/PI will renegotiate effort on other grants, if necessary, to permit required effort on the RPA. Note that a change in effort of more than 25% may require programmatic approval from other NIH ICs. A temporary reduction in effort may be approved under circumstances such as medical conditions, disability, or personal or family situations.
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 fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided 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.
1. Criteria
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
An RPA is intended to support most of the NINDS-related research in an investigator's laboratory or research group for a sustained period of time, facilitating increased funding stability, reduced administrative burden, and a more flexible research environment enabling more ambitious, creative and/or long-term research. RPA applicants are expected to provide an overview of their proposed research program, the scientific questions or challenges they intend to address and a general description of approaches and tools that might be used to address them.
Accordingly, reviewers will emphasize the following:
- Evidence of contributions made by the PD/PI commensurate with the investigator's career stage, particularly within the past 5 years that advance his or her respective field
- Potential for the PD/PI's research impact to continue at the same level over the course of the RPA
- Suitability of the R35 mechanism, with its unique flexibility and facilitation of longitudinal continuity to advance the investigator's research program
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
In addition, for applications involving clinical trials
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Specific to this FOA: Does the proposed research program address a problem that is sufficiently comprehensive and substantial to be appropriate for long-term pursuit? Is the proposed research program adequately broad and does it have potential to move the field forward?
Rigor of Significance
Does the application adequately describe whether prior research that serves as the key support for the proposed project employed rigorous practices such as minimization of potential experimenter biases, robust experimental designs, transparent reporting of results and analyses, and careful interpretation? How does the application address ambiguity, weaknesses, or limitations in rigor of the prior research, if applicable?
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?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Specific to this FOA: Has the PD/PI demonstrated productivity in the proposed field of study appropriate for the applicant’s stage of career? Critical life events such as family care responsibilities, serious illness or disability, or military service should be considered. Has the PD/PI shown evidence of being adaptable, able to recognize new opportunities and explore new areas of scientific inquiry, and open to the use of new tools, technologies, and strategies, as appropriate? Does the PD/PI have a record of conducting rigorous, reproducible, and transparent research? Has the PD/PI proposed an appropriate commitment of time and effort for the proposed work? Does the PD/PI have a record of professional service, including evidence of high-quality mentorship of undergraduate, graduate, or medical students, postdoctoral or clinical fellows, or junior faculty? Does the PD/PI have a record of mentoring individuals from diverse, underrepresented populations?
Does the PD/PI have a track record of creativity and innovation? Will the increased stability and flexibility of the RPA mechanism enable continued high innovation or more innovative and adventurous approaches to the scientific issues described in the application?
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?
In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
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?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Specific to this FOA: Will the proposed research benefit from the unique features of the R35's long term and flexible approach to funding? Is there a sound basis for the proposed level of effort?
Rigor of Approach
Does the proposed research incorporate adequate methodological rigor where applicable, including, but not limited to, clear rationale for the chosen model(s) and primary/secondary endpoint(s), clear descriptions of tools and parameters, blinding, randomization, adequate sample size, pre-specified inclusion/exclusion criteria, appropriate handling of missing data and outliers, appropriate controls, preplanned analyses, and appropriate quantitative techniques? Do the applicants clearly indicate the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications?
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?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Specific to this FOA: Are efforts to enhance diversity through an environment that promotes inclusion of individuals with a wide variety of backgrounds and perspectives well-described and likely to contribute to the success of the project?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
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.
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.
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.
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.
Not Applicable
Not Applicable
Not Applicable
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
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.
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).
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).
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.
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 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.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned on the basis of established PHS referral guidelines. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council (NANDSC). 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.
- Scientifically diverse perspectives w?i?t?h?i?n the applicant's laboratory.
- Note that lower funding priority may be given to applicants with significant unrestricted research support.
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 recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. 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.
It is anticipated that the terms of award will include, but not be limited to, the following:
- Relinquishment and/or deobligation of funds from NINDS grants awarded to the PI as described in Part 2, Section I and prorated proportional financial deobligation of the PI's contribution to MPI grants according to the initial distribution of committed effort.
- Carryover of an unobligated balance for budgets greater than 25% from one budget period to another budget period will require Grants Management Officer prior approval.
- The initial no-cost extension can be done by the grantee in eRA Commons. Any subsequent no-cost extension will require Grants Management Officer approval.
- Change of PD/PI will not be allowed.
- Change of grantee institution (with NIH approval) will be allowable if the receiving institution agrees to all of the required terms.
- It is expected that the PD/PI will renegotiate effort on non-NINDS NIH grants, if necessary, to permit a minimum of 6 person months to be devoted to the RPA.
The award period will be for 8 years contingent upon administrative review of RPRR submitted materials, and NANDS Council approval prior to the year -06 start date. An administrative supplement request for a budget increase for years 6-8 may also be submitted concurrent with the RPPR.
For this administrative review, six months prior to the end of the year-05 budget period, PD/PIs are required to submit the following as an attachment with their year five RPPR:
1. 2-3 page summary of the research accomplishments of the first 5 years of the R35 award which justifies continuation of the research program for three additional years
2. List of publications and/or other evidence of impact (e.g. translational activities, mentoring, service) that have resulted from R35 funding (must be related to the grant’s goals) along with a description of the impact of the 3 most significant publications (no more than 1 page)
3. A description of the scientific rigor of the work (no more than 1 page)
4. If an administrative supplement is being requested for years -06 to -08, a one to two paragraph justification delineating the budget being requested in the associated administrative supplement.
5. The administrative supplement for years -06 to-08 of the award
Although no RPA budget will exceed $750K direct costs (DC) per year, the administrative supplement request can be up to a $150K DC per year for the duration of the award. When evaluating the administrative supplement, NINDS will consider the following factors:
1) the PI’s other support (including non-NIH and non-Federal funding);
2) the career stage of the PI;
3) the progress of the research program during the first five years of the R35 award; and
4) the size of the initial R35 award.
5) PIs with significant other support will generally not receive budget increases. More specific guidance will be provided to R35-funded investigators in advance of the Year 6 administrative review.
Further details may be provided in the NOA.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
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, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, 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 (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.
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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
3. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
a) Under Section 6.2 B.1 What are the major goals of the project? Note that the goals of the program of research supported by the RPA are broader than the specific aims of a single project and should be appropriately described. In addition to the scientific goals, describe the goals of enhanced mentoring of trainees and other research personnel that this award facilitates. If the goals of the RPA have changed, complete section B.1.a. Provide a rationale for the changes in the context of the originally proposed research program and further contributions to the field, and an explanation of how the research continues to fit within NINDS mission interests.
b) Under Section B.2, in addition to the instructions, emphasize how the work continues to be innovative and of high impact.
c) Under section D.2.c. additional information, indicate if there have been changes in Other Support. In addition to the revised Other Support page, include an explanation of the relationship of the new awards to the activities supported by the RPA.
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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Alisa Schaefer, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
E-mail: [email protected]
Ernest Lyons, Ph. D.
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]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.
and Human Services (HHS)
