Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title
Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences (UG3/UH3 Clinical Trial Not Allowed)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
Reissue of PAR-19-171
Related Notices
  • NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
  • June 16, 2022 - Notice of Corrected Application Forms and Extended Receipt Date for PAR-22-076 "Prospective Observational Comparative Effectiveness Research in Clinical Neurosciences (UG3/UH3 Clinical Trial Not Allowed)". See Notice NOT-NS-22-110
Funding Opportunity Announcement (FOA) Number
PAR-22-076
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.853
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage grant applications for investigator-initiated prospective observational comparative effectiveness research (CER) to the National Institute of Neurological Disorders and Stroke (NINDS) (note: only prospective observational studies will be considered). The study must address questions within the mission and research interests of the NINDS and may evaluate preventive strategies, diagnostic approaches, or interventions including drugs, biologics, and devices, or surgical, behavioral, and rehabilitation therapies. NINDS is particularly interested in pragmatic study designs that utilize a cost-effective means of prospectively collecting observational data important to current clinical practice.

Key Dates

Posted Date
March 21, 2022
Open Date (Earliest Submission Date)
New Date June 19, 2022 (Original Date: May 18, 2022)
Letter of Intent Due Date(s)

30 days prior to application due date.

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
July 19, 2022 July 19, 2022 September 07, 2022 * November 2022 January 2023 April 2023
October 18, 2022 November 18, 2022 January 07, 2023 * March 2023 May 2023 July 2023
February 17, 2023 March 17, 2023 May 07, 2023 * July 2023 October 2023 December 2023
June 19, 2023 July 18, 2023 September 07, 2023 * November 2023 January 2024 April 2024
October 18, 2023 November 17, 2023 January 07, 2024 * March 2024 May 2024 July 2024
February 20, 2024 March 15, 2024 May 07, 2024 * July 2024 October 2024 December 2024
June 18, 2024 July 18, 2024 September 07, 2024 * November 2024 January 2025 April 2025
October 18, 2024 November 15, 2024 January 07, 2025 * March 2025 May 2025 July 2025
February 19, 2025 March 18, 2025 May 07, 2025 * July 2025 October 2025 December 2025

A new application forms package which can accommodate all the budget periods has been posted in Grants.gov identified by a Competition ID of "FORMS-G-REVISED'. If you initiated an application using the original (FORMS-G) package, you must move the application information to the FORMS-G-REVISED application package to successfully submit.

Note: ASSIST, Workspace and many institutional system-to-system solutions allow application data to be easily copied from one application package to another. In this case, the "copy" feature will move all but your budget data to the new form package. Contact appropriate support team for assistance (ASSIST -eRA Service Desk; Workspace -Grants.gov Contact Center). Please use these instructions starting with the July 19, 2022 receipt date and subsequent due dates.

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.

Expiration Date
May 08, 2025
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background
The “gold standard” of evidence for establishing the utility and success of therapeutic interventions is the randomized clinical trial (RCT). However, challenges in the design and execution of definitive RCTs and obstacles to implementation of trial results often limit their use in specific settings. One example of an obstacle is the “ideal” context in which the trial is conducted (efficacy), rather than a “real world” setting (effectiveness) where the intervention would be implemented eventually. Even a well-designed efficacy RCT may be difficult to interpret because of exceptions from randomization, such as dropouts, cross-overs, or missing data. Given the high cost of traditional RCTs and their potential limitations, other approaches to developing rigorous evidence to support clinical decision-making are needed. One example of this approach is the prospective observational comparative effectiveness study design.

The purpose of this funding opportunity announcement (FOA) is to encourage grant applications for investigator-initiated prospective observational comparative effectiveness studies. For the purposes of this FOA, comparative effectiveness research (CER) is defined as the conduct of research comparing the benefits and harms of different existing interventions and strategies to prevent, diagnose, treat and monitor health conditions in “real world” settings (modified from Federal Coordinating Council for Comparative Effectiveness Research. Report to the President and the Congress. US Department of Health and Human Services, 2009; https://osp.od.nih.gov/wp-content/uploads/FCCCER-Report-to-the-President-and-Congress-2009.pdf). The NINDS has a longstanding interest in CER. CER typically utilizes “real world” settings to compare existing interventions or strategies that have been studied individually in randomized controlled trials (RCT), that are commonly used clinically despite the absence of evidence from prior controlled trials, or that are used in settings where patients might have treatment preferences, despite equipoise among medical care providers. A comparative effectiveness approach may also be useful to:

  1. determine the optimal patient population or situation for a given intervention;
  2. determine outcomes when it is unethical, excessively costly, or not feasible to perform a RCT;
  3. estimate specific parameters for study in a future RCT;
  4. determine whether a specific treatment adds “value” (i.e., is cost effective), compared to standard of care treatments; or
  5. determine outcomes that can be applied in registries where treatments or standard of care may change over time.


Broadly speaking, CER can be performed using a variety of methods, including prospective observational studies, clinical trials, or structured evaluation of existing evidence from registries, electronic health records, and other databases (e.g., meta-analyses, systematic reviews, modeling). An important component of CER is the application of analytical strategies, such as multivariable regression, propensity score analysis, and instrumental variable analysis, to adjust for known inherent biases resulting from lack of randomization.


For this FOA, only prospective observational studies will be considered for funding. Other types of CER studies may be submitted to other FOAs, if applicable. The grant mechanism used to support this funding announcement is a cooperative agreement (UG3/UH3) mechanism with two phases. The initial milestone-driven planning phase (UG3) will last for up to 2 years, with possible transition to a prospective observational study phase of up to 5 additional years (UH3). Only UG3 projects that have met scientific milestones and feasibility requirements will be approved to transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application. The UG3 phase for observational studies will permit both scientific and operational planning activities. The UH3 phase of the award will support the conduct of investigator-initiated prospective observational studies.
The UG3 award (Planning Phase) will provide up to 2 years of support for scientific and operational planning activities required (not yet completed) to prepare for conduct of a subsequent CER study. The UH3 award (Implementation Phase) will provide up to 5 years of support for conduct of the CER study in accordance with activities planned in the UG3 phase. This study should have an overall hypothesis, be milestone-defined, and have the potential for high impact within the research mission of NINDS. The study must meet all applicable NIH and Office of Human Research Protections (OHRP) policy requirements.


UG3/UH3 Transition: At the completion of the UG3 planning phase, the applicant will be required to submit an RPPR that includes the list of completed milestones (developed in collaboration with the PI as part of the initial Notice of Award) to progress to the UH3 implementation phase. These UH3 transition requests will undergo administrative review by NIH staff to determine whether the study will be awarded the implementation phase (UH3). Transition decisions will be based on achievement of study milestones, readiness to conduct the UH3 study, feasibility of completing the UH3 study, availability of funds, and program priorities.
Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee support of the UH3 implementation phase. UH3 funding is dependent on NINDS program priorities and availability of funds. In addition, applicants should understand that transition to the UH3 phase of the project will occur only if the administrative review process determines that the UG3 planning milestones have been successfully met and that the UH3 phase can proceed with confidence of success.


Additional Information
Each NINDS UG3/UH3 Cooperative Agreement application may only be used to propose the planning and implementation of a single prospective observational study.
Studies of outcomes in populations that typically are subject to health disparities and under-representation in clinical trials (including, but not limited to, racial and ethnic minorities, persons with disabilities, children, the elderly, and patients with multiple chronic conditions) are particularly encouraged (https://www.healthypeople.gov/2020/about/foundation-health-measures/Disparities).

Diseases, disorders, and conditions that are considered to be under-researched (particularly with respect to burden of illness) are also encouraged.

Applicants should take note of the following special requirements and considerations:

  1. Scope. The scope of this FOA includes prospective observational studies (for example, studies of typical care when multiple treatment modalities are used, natural experiments with changes in medical care or policies, studies where care differs based on geography, or cohort-based studies, among others).

    Limited studies of outcomes that are not included in typical care may be included (e.g., limited implementation of neuropsychological studies) as part of a fully-powered secondary hypothesis.

  2. The following types of studies are considered out of scope for this FOA:
  • Clinical trials, including network-based studies (e.g., NeuroNEXT, StrokeNet, or SIREN). For a list of NINDS clinical trial Funding Opportunity Announcements, see https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Clinical-Research )
  • Pooled secondary analyses of existing large databases and/or cohorts, meta-analyses, systematic reviews, and simulations (applicants should consider applying under PA-20-185 or PA-21-219)
  • Dissemination and implementation research (applicants should consider applying under PAR-19-274)
  • Systematic reviews or meta-analyses of existing clinical trials. For this type of study, applicants should consider applying under PA-20-185 or PA-21-219, as appropriate.

3. Relationships with Patient Groups: Applicants are strongly encouraged to establish relationships with patient groups and solicit their input on recruitment, the clinical meaningfulness of the question under study, the relevance of the proposed clinical outcomes, and approaches to minimizing the burden on study subjects. There is particular interest in

underrepresented and underserved populations patient and community groups.

4. IRB documentation: IRB approval of the protocol and informed consent are not required at the time of application submission unless the UG3 phase involves human subjects; it is required prior to UH3 (Implementation Phase) funding. Applications must comply with the Federal sIRB mandate (45 CFR 46.114) and the NIH Single IRB Policy for multi-site research, if applicable (https://grants.nih.gov/policy/clinical-trials/single-irb-policy-multi-site-research.htm). NINDS encourages investigators to begin these processes as early as possible. NINDS also will require documentation of any other necessary regulatory approvals (e.g., Recombinant DNA Advisory Committee) prior to funding, if applicable.

5. NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including:

6. Innovative Technologies: Applicants are encouraged to consider utilizing (at least experimentally) digital/mobile/sensor technologies and web-based systems to facilitate data collection (including data collection in a continual, contextual, real-world setting) and to enhance protocol adherence. Innovative statistical approaches are also encouraged, when appropriate.

7. Consultation with NINDS: Applicants are strongly encouraged to consult with NINDS Scientific/Research staff well before an application is developed (see Section VII, Agency Contacts).This early contact will provide an opportunity to clarify NINDS policies and guidelines as well as to discuss how to develop an appropriate project timeline and milestone plan, which is subject to peer review. The NINDS considers program priorities and scientific overlap with other funded projects. Scientific/Research contacts are also available to discuss strategies for recruitment and inclusion of women and minorities.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

Funds Available and Anticipated Number of Awards

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

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project.

Award Project Period

Up to 2 years for the UG3; up to 5 years for the UH3.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

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

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

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

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • 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.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, 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).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Adam L. Hartman, MD
Telephone: 301-496-9135
E-mail: adam.hartman@nih.gov

Page Limitations

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

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Significance: There should be a justification of why an RCT cannot be performed to answer the main experimental question(s) posed in the application. As the nature of CER is a comparison of treatments, there should be a justification for selection of the proposed interventions from amongst the many available options. The goal is to target effectiveness (i.e., "real-world" environment with few inclusion/exclusion criteria) rather than efficacy (i.e., ideal conditions with limited numbers of patients with strict inclusion/exclusion criteria), so the proposed study should have the potential to inform decisions by key stakeholders, including patients, clinicians, and/or policymakers. Study outcomes should target the intended population for the intervention because of the "real world" nature of the investigation. Similarly, the application should address priorities articulated by patients, clinicians, and/or policymakers and the priorities of these groups should be gauged prior to submission and reported in the application. The application should address an area of need, such as an underserved population or disease entity.

Investigator(s): The investigator team should be qualified in terms of experimental design, study execution, data handling, and statistical analyses/interpretation of CER-derived data. For a multicenter study, the organizational structure should be appropriate and the application should identify a core of potential center investigators and staffing for a clinical and data coordination.

UG3 Approach: The application should include descriptions of the following:

  1. Processes for including proposed international clinical sites, if applicable.
  2. Data management system and case report forms, incorporating applicable NINDS Common Data Elements;
  3. Development of tools for data and quality management;

UH3 Approach: The application should discuss the following:

  1. Enrollment, retention, plans to minimize losses to follow-up, and acceptable attrition rates;
  2. Plans for site activation, execution of contracts and training of additional clinical sites, including any international sites, if applicable;
  3. Appropriateness of the proposed patient cohort for the study question at hand;
  4. As interventions proposed for study in this CER FOA already have been used in practice or already studied in efficacy trials, a description of optimal use of existing data that serve as the background/rationale for the study;
  5. Safety monitoring, which may include a Medical Monitor, Study Monitoring Committee, or an Observational Study and Monitoring Board, when appropriate.
  6. A clear (and when appropriate, innovative) statistical analysis plan, and if applicable, a decision rule that will allow a clinically-relevant and focused recommendation at the end of the study;
  7. If applicable, the decision rule that accounts for efficacy and safety, thus addressing the optimal benefit vs. risk;
  8. Data quality and quality assurance, including a description of how missing data will be handled;
  9. If using a noninferiority design, the noninferiority margin and justification for that margin;
  10. A critical assessment of the implications of study results in terms of the statistical limits (i.e., probability distribution) of the data;
  11. If proposing multisite recruitment or using recruitment from different sources (e.g., different cohorts), a description of how these populations differ;
  12. Potential confounders (i.e., appropriate analyses should be proposed to account for potential confounders, including a propensity analysis, risk-adjusted regression, or instrumental variable analysis, etc.);
  13. If applicable, a plan to use common data elements (NINDS, NIH-funded CDEs or other data standards) and a plan to allow harmonization of outcomes with similar existing or future projects.
  14. Recruitment and Retention Plan

    Applicants must include a discussion of the ability of sites to recruit and retain the proposed number of participants, including women, underrepresented minorities, and individuals across the lifespan. Evidence should be provided that relevant stakeholders (e.g., potential participants, referring and treating physicians, diverse patient groups) have equipoise, view the question to be important and consider the study acceptable.

Environment: The proposed sites should be sufficient in number and have resources to meaningfully contribute to the study. Statistical support should be adequate to manage the data and analyses required for CER. There should be a clear plan for management of a multisite team, if applicable.

Study timeline and milestones:

UG3: The application should specify the timeline of the following milestones, which need to be completed before approval to enter the UH3 phase:

  1. Development of recruitment and retention strategies
  2. Development of data management system and case report forms, incorporating applicable NINDS/NIH or other Common Data Elements;
  3. Development of tools for data and quality management;
  4. Finalization of protocol, manual of procedures, consent forms, and data management plan;
  5. Finalization of planned analyses (including interim analyses, if appropriate);
  6. Protocol approval from a Medical Monitor, Study Monitoring Committee, or an Observational Study and Monitoring Board, when appropriate;
  7. Initiation of contracts and training of clinical site personnel (NINDS expects the initiation of all study sites to occur in the start-up stage; if a large number of sites is needed, a plan that describes how additional sites will be added after the initiation of the study should be included);
  8. Initiation of processes for including proposed international clinical sites, if applicable;
  9. Plans for site activation, execution of contracts and training of additional clinical sites, including any international sites, if applicable.

UH3: The application should specify the timeline of the following milestone:

  1. Interim (if applicable) and final data analyses.

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, must address a Data Sharing Plan as part of the Resource Sharing Plan (budgets also must include expenses associated with data sharing).

  • Data Submission and Sharing Policies for the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System Data from Traumatic Brain Injury clinical research studies must be submitted if they meet the following criteria: (1) TBI-related clinical trials; (2) all unsolicited clinical TBI research grants with a budget greater than or equal to $500,000/year in direct costs; (3) ancillary studies, regardless of budget, to either TBI-related clinical trials or clinical TBI research grants with budgets greater than or equal to $500,000/year in direct costs; and (4) clinical TBI research grants awarded under funding opportunity announcements (FOAs) with specific requirements for FITBIR data submission. In addition, any TBI genomic studies that generate large-scale genomic data, regardless of the size of the budget, or NIH grant funding mechanism, should follow the guidance of the NIH GDS Policy on data sharing. For more information read the Notice of Modification of the Data Submission and Sharing Policies for the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System https://grants.nih.gov/grants/guide/notice-files/NOT-NS-17-029.html

  • Autism research involving human subjects funded by NINDS are required to deposit all raw and analyzed data (including, but not limited to, clinical, genomic, imaging, and phenotypic data) into the NDA infrastructure (https://grants.nih.gov/grants/guide/notice-files/NOT-MH-20-010.html).

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.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Applicants must include a discussion of the ability of sites to recruit and retain the proposed number of participants, including women, underrepresented minorities, and individuals across the lifespan. Evidence should be provided that relevant stakeholders (e.g., potential participants, referring and treating physicians, diverse patient groups) have equipoise, view the question to be important and consider the study acceptable.

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human participants research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Investigators are encouraged to consult the NIH CDE Repository and describe in their applications any use they will make of NIH-supported CDEs in their projects, when applicable. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological diseases), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Repository Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

 

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?

Can this study be done as a RCT? Has the applicant provided sufficient justification for a CER (rather than an RCT) approach? As the goal is to target effectiveness (rather than efficacy), does the proposed study have the potential to inform decisions by key stakeholders, including patients, clinicians, and/or policymakers? Will study outcomes target the intended population for the intervention? Is the application responsive to priorities articulated by patients, clinicians, and/or policymakers? Have the priorities of these groups been gauged prior to submission? Does the application address an area of need, such as an underserved population or disease entity?

 

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?

Is the investigator team qualified in terms of experimental design, study execution, data handling, and statistical analyses/interpretation of CER-derived data? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators with appropriate staffing?

 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are the analysis plan and statistical approach innovative?

 

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?

As a CER study, is there good justification for selection of the proposed interventions (from amongst the many available options)? As interventions proposed for study in this CER FOA already have been used in practice or already studied in efficacy trials, is there optimal use of existing data that serve as the background/rationale for the study? Is the proposed patient cohort appropriate for the study question at hand? Is there a clear statistical analysis plan, and if applicable,a decision rule that will allow a clinically-relevant and focused recommendation at the end of the study? If applicable, does the decision rule account for efficacy and safety, thus addressing the optimal benefit vs. risk? Does the application describe data quality and quality assurance,how missing data will be handled, and acceptable attrition rates? If using a noninferiority design, are the noninferiority margin and justification for that margin described? Are implications of study results assessed critically in terms of the statistical limits (i.e., probability distribution) of the data? If proposing multisite recruitment or using recruitment from different sources (e.g., different cohorts), does the application describe how these populations differ? Are potential confounders considered (i.e., are appropriate analyses proposed to account for potential confounders, including a propensity analysis, risk-adjusted regression, or instrumental variable analysis, etc.)? If applicable, does the application propose to use NINDS common data elements , and is there a plan to allow harmonization of outcomes with similar existing or future projects?

How well does the Data Sharing Plan provide a summary of the shared data, a description of the data standards, a plan for the data archiving, and a timeline for data submission to the archive and sharing data with the research community?

 

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?

Are the proposed sites sufficient in number and do they have resources to meaningfully contribute to the study? Are resources for statistical support adequate to manage the data and analyses required for CER?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

 

 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)?  Are the UG3 and UH3 milestones specific, measurable, attainable, realistic, and timed appropriately?

 

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.

Study Population Characteristics


Inclusion of Women and Underrepresented Minorities

Recruitment and Retention Plan

Evidence should be provided that relevant stakeholders (e.g., potential participants, referring and treating physicians, diverse patient groups) have equipoise, view the question to be important and consider the study acceptable.

 

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.

 

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

 

Not Applicable.

 

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

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

 

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) Sharing Model Organisms; and (2) 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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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.

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75, 2 CFR Part 200, and other HHS, PHS and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, and "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipientsis anticipated during the performance of the activities. Under the cooperative agreement, the NIH's purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipientsfor the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

  • The Program Director/Principal Investigator will have the primary responsibility to define research objectives and approaches and to plan, conduct, analyze and publish results, interpretation and conclusions of their studies and for providing overall scientific and administrative leadership for the research project.
  • The PD/PI will oversee all aspects of the organization and execution of the studies outlined in the application and approved by NINDS after peer review.
  • Recipientshave primary and lead responsibilities for the project as a whole, including any modification of study design, the conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by the action of the primary leadership committee.
  • Recipientswill be responsible for reporting recruitment data to the NINDS Recruitment Planning & Monitoring System (RPMS).
  • Recipientswill be responsible for putting all study materials and procedure manuals into the public domain. Recipientsare expected to publish and publicly disseminate results, data and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NINDS/NIH.
  • Recipientswill be responsible for obtaining prior written approval of the NINDS Grants Management Specialist in consultation with the NINDS Program Officer for any change in any of the key personnel identified in the Notice of Grant Award.

Recipientswill retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NINDS Project Scientist will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards, as described below.  In addition to the Project Scientist, an NINDS Administrative Program Director will be responsible for programmatic stewardship of the award and will be named in the award notice.  This stewardship will include detailed monitoring of trial progress and milestones as described below.  A third NINDS Program Official from the Office of Clinical Research will serve as the NINDS liaison to the NINDS appointed Data and Safety Monitoring Board.

The NINDS Project Scientist will:

  • Have access to data generated under this Cooperative Agreement and may periodically review the data and administrative progress reports.  Program staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, recipients will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
  • Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from NINDS grantees and contractors, advising in management and technical performance, or participating in the preparation of publications.
  • Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team, which may include attendance at the DSMB and related committee meetings.

NINDS reserves the right to terminate or curtail the study (or an individual award) under a range of scenarios including but not limited to (a) failure to implement the study protocol, (b) a substantial shortfall in subject recruitment, follow-up, data reporting and dissemination, quality control, or other major breaches of the protocol, (c) substantive changes in the agreed-upon protocol with which NINDS does not concur, (d) reaching a major study objective substantially ahead of schedule with persuasive statistical evidence, (e) human subject safety or ethical issues that may dictate a premature termination, or (f) a change in the state of science that changes equipoise or has other significant impacts on the relevance of the question.

Areas of Joint Responsibility include:

  • The NINDS Project Scientist will serve on the primary leadership committee.  In addition, the Project Scientist, or other NINDS Program Officials, may serve on other study committees regarding recruitment, intervention, follow-up, quality control, protocol adherence, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.  The NINDS Project Scientist will have voting membership on the primary leadership committee and its subcommittees.
  • Each full member will have one vote.  Recipiente members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee. 

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Continuation of Funding:

The award and administrative continuation of funding are subject to milestones to be specified in the notice of grant award according to NINDS policies (see NINDS policy for continuation of Phase 3 clinical trials (NOT-NS-10-009). The Terms and Conditions will include site activation and recruitment milestones, accrual goals for women and minorities (as appropriate) and any other identified requirements for completion of the approved research.

As with any award, continuation is conditional upon satisfactory progress, even during the period recommended for support. If recruitment falls significantly below the projected milestones at any time, the NINDs may consider ending support and implementing a phase-out of the award. The NINDS retains the option to obtain periodic external peer review of progress.

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 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.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

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

Scientific/Research Contact(s)

Adam L. Hartman, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
E-mail: adam.hartman@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.

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