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
Clinical Trial Readiness for Functional Neurological Disorders (U01 Clinical Trial Optional)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-22-053
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.853
Funding Opportunity Purpose

Functional Neurological Disorders (FNDs) are characterized by symptoms of altered voluntary motor or sensory function with clinical findings providing evidence of incompatibility between the symptoms and recognized neurological or medical conditions. FNDs are highly prevalent and associated with significant morbidity, health care costs, and even mortality. In some respects, this group of conditions sits at the intersection of neurology and psychiatry, but the majority of cases first come to the attention of neurologists. Management is complex and requires interdisciplinary approaches. Given the disability caused by the symptoms, and the high cost in healthcare utilization and loss of productivity, FNDs amount to a significant missed opportunity for therapeutic intervention and therefore, a healthcare crisis.

Diagnosis and management of FNDs remain very challenging. Diagnostic criteria have been proposed but they are not universally agreed upon. Diagnosis is based on positive clinical findings, and can be supported by laboratory or ancillary investigation findings. Certain FND subtypes are more difficult to correctly diagnose than others. More importantly, laboratory-supported diagnosis is possible, and biomarkers can be developed, but significantly more research is needed in these areas to advance clinical management of FNDs.

Therapies exist and have been studied in select populations but gathering high-level evidence through clinical trials is hampered by limitations in available outcome measures. Differential responses to treatments have been recorded, and thus, prediction of aggregate treatment response has been difficult.

This FOA invites researchers to submit prospective clinical projects that address critical needs for clinical trial readiness in FNDs. Projects appropriate for this FOA include the validation of biomarkers, endpoints and clinical outcome assessments (COA) that are fit-for-purpose and have a defined context of use for clinical trials. Projects involving biomarker discovery or early validation should apply to the relevant FOAs (PAR-19-315, PAR-21-056, PAR-21-057, PAR-21-058, PAR-21-059).

The initiative will promote partnerships among academic investigators, industry, and patient groups, and will encourage interactions with the Food and Drug Administration (FDA).

Key Dates

Posted Date
November 02, 2021
Open Date (Earliest Submission Date)
January 05, 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
February 05, 2022 * March 05, 2022 * Not Applicable July 2022 October 2022 December 2022
June 05, 2022 * July 05, 2022 * Not Applicable November 2022 January 2023 April 2023
October 05, 2022 * November 05, 2022 * Not Applicable March 2023 May 2023 July 2023
February 05, 2023 * March 05, 2023 * Not Applicable July 2023 October 2023 December 2023
June 05, 2023 * July 05, 2023 * Not Applicable November 2023 January 2024 April 2024
October 05, 2023 * November 05, 2023 * Not Applicable March 2024 May 2024 July 2024
February 05, 2024 * March 05, 2024 * Not Applicable July 2024 October 2024 December 2024
June 05, 2024 * July 05, 2024 * Not Applicable November 2024 January 2025 April 2025
October 05, 2024 * November 05, 2024 * Not Applicable March 2025 May 2025 July 2025

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
November 06, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

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

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background:

The prevalence and system-level costs of FNDs make this an area of great need in Neurology. NINDS supports research across a wide spectrum of neurological disorders. While some limited success has been reported with various treatment modalities in FNDs, clinical trials to obtain higher level of evidence are needed to impact care. To this end, it is critical that outcome measures and biomarkers for this set of conditions be optimized and standardized across the field. Clinical trials employ biomarkers and/or COA measures to determine whether interventions are safe, efficacious or effective in the study cohort(s).

The challenges to developing and/or validating outcome measures are unique for FNDs, given the heterogeneity and variability of symptoms, the influence of subjective factors, and the prevalence of confounding comorbidities. This prompts the need for research focused specifically on biomarkers, clinical endpoints, and COAs in FNDs.

This FOA invites applications for support of prospective clinical projects that address clinical trial readiness in FND. We define clinical trial readiness as having established, valid biomarkers and COAs that are fit-for-purpose within the context of planned clinical trials.

Terminology:

This FOA uses terminology to describe this type of research as defined in the BEST (Biomarkers, EndpointS, and Other Tools) Resource, which was developed by the FDA-NIH Biomarker Working Group. Investigators are encouraged to use the terms below, where appropriate in their applications. Guidance to reviewers will include these definitions as a way to promote consistent evaluation of the applications. (See https://www.ncbi.nlm.nih.gov/books/NBK338448/ for reference to the BEST Resource's glossary for the following definitions.)

Biomarker – A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Molecular, histologic, radiographic, or physiologic characteristics are types of biomarkers. Categories of biomarkers include: Susceptibility/risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, safety.

Clinical outcome assessment (COA) – An assessment of an outcome that reflects how an individual feels, functions or survives. The four types of COAs are clinician-reported, observer-reported, patient-reported, and performance outcomes.

Clinical endpoint: In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial.

Context of Use (COU) – A statement that fully and clearly describes the way the medical product development tool is to be used and the medical product development-related purpose of the use. Considerations involved in defining the COU can include: biomarker modality and method of detection, clinical population characteristics, unmet need for the new biomarker and type of biomarker (response prediction, stratification, prognostic, diagnostic, target engagement, etc).

Concept – In a regulatory context, the concept is the aspect of an individual’s clinical, biological, physical, or functional state, or experience that the assessment is intended to capture (or reflect).

Validation – A process to establish that the performance of a test, tool, or instrument is acceptable for its intended purpose.

Analytical Validation: Establishing that the performance characteristics of a measurement are acceptable in terms of its sensitivity, specificity, accuracy, precision, and other relevant performance characteristics using a specified technical protocol (which may include sample collection and standardization procedures). Although the goal of analytical validation is to ensure a rigorous clinical conclusion, the level of analytical rigor that is necessary depends upon the characteristics of the biomarker, the detection technology, the type of clinical question (exploratory/informational) or its intended use as a biomarker (diagnostic, predictive, pharmacodynamic, etc). Analytical validation establishes the measurement's technical performance, but does not validate the usefulness of the measurement. The goal for analytical validation should be that the biomarker measurement meets FDA analytical performance criteria https://www.fda.gov/downloads/drugs/guidances/ucm368107.pdf within the scope of the intended Context of Use.

Clinical Validation: Establishing that the biomarker acceptably identifies, measures or predicts the concept of interest.

Construct Validity – A process to establish, using quantitative methods, the extent to which the relationships among items, domains, and concepts of a clinical outcome assessment conform to a priori hypotheses concerning logical relationships that should exist with other measures or characteristics of patients and patient groups.

Content Validity – A process to establish from qualitative research the extent to which the clinical outcome assessment instrument measures the concept of interest including evidence that the items and domains of an instrument are appropriate and comprehensive relative to its intended measurement concept, population, and use.

Clinical Utility: The conclusion that a given use of a biomarker will lead to a net improvement in health outcome or provide useful information about diagnosis, treatment, management or prevention of a disease. Clinical utility includes the range of possible benefits or risks to individuals and populations.

Scope:

Applications should propose studies that validate candidate COA measures and biomarkers, with a goal and plan for implementation within their context of use in upcoming trials. Investigators are encouraged to use or modify existing resources, validate existing tools in specific disease populations, or add components to existing disease-specific tools (such as symptom scales).

Applications responsive to this FOA may also propose prospective clinical studies aimed at validating COA measures or scales.

Studies proposing only biomarker validation should apply to the NINDS FOAs on biomarker validation.

The types of biomarkers and COAs considered would largely fall under the broad categories defined by the Biomarkers Definitions Working Group: diagnostic tools for identifying patients with disease; tools for staging or classifying the extent of the disease; indicators of disease prognosis; predictors and monitoring tools for response to an intervention.

Clinical Validation can include the following metrics with use of FDA guidance standards appropriate for the context of use:

  • Demonstration of association of the result of the biomarker assay with a clinical endpoint (e.g., survival, response, disease presence or absence) in samples or data from patients that have been exposed to a uniform intervention or that have or will develop a disease or disorder
  • Definition of the sensitivity and specificity of the assay result within the context of the defined clinical endpoint and clinical population
  • Estimation of the prevalence of the marker within subjects or patients for the intended clinical context
  • Establishment of an appropriate cut-off or threshold for the assay using suitable statistical analysis

Examples of studies intended to be supported through this FOA include, but are not limited to, the following:

  • Determination or expanded determination of the Context of Use for the biomarker or COA measure.
  • Optimization of the detection method, COA or endpoint measure with clinical intervention such as pharmacodynamic/response biomarkers, predictive biomarkers, safety biomarkers, or monitoring biomarkers
  • Studies focused on improving standardization or harmonization of assays among laboratories for use in clinical trials
  • Studies aimed at the validation of clinician-reported, observer-reported, patient-reported, and/or performance outcomes with defined contexts of use in specific FND populations
  • Studies aimed at the validation of COA measures and one or more biomarker(s) that can be of any category relevant to clinical trials including safety, predictive, prognostic or pharmacodynamic/response.
  • Studies to validate candidate biomarkers by analyzing the correlation of biomarkers with COA measure data collected in the same cohort.
  • Studies that, through the validation of COA measures or biomarkers, collect the data necessary to determine appropriate participant inclusion/exclusion criteria for upcoming clinical trials.
  • Studies that, through the validation of COA measures or biomarkers, collect the data needed for accurate power calculations or determining the appropriate duration of upcoming clinical trials.
  • Studies that demonstrate responsiveness of biomarkers or COAs through the observation of patients who are receiving treatment as part of their clinical care.
  • Ancillary studies that aim to validate COA measures or biomarkers by adding them to ongoing clinical studies (or trials) supported through other sources of funding.

Collaborations:

Multi-disciplinary collaboration among scientific investigators, assay developers, clinicians, statisticians, consultants, and clinical laboratory staff are strongly encouraged. Projects proposed for this FOA will utilize multi-site design as applicable, and standardized data stewardship to ensure that data is reusable and accessible.

Investigators are encouraged to form collaborations with individuals knowledgeable in the FDA qualification process as well as those familiar with the process of analytical validation, including statistical design and analysis experts.

Biospecimen collection and banking:The NINDS encourages standardized human biospecimen collection protocols and banking at the designated NINDS repository, BioSpecimen Exchange for Neurological Disorders (BioSEND). NINDS policy requires inclusion of associated costs within application budgets. Investigators are therefore strongly encouraged to contact the BioSEND for updated pricing and policies early in the application process, and to include related costs in the budget. All biospecimens collected and banked with BioSEND must come from individuals who have consented to banking and sharing broadly with academia and industry.

Leveraging Existing Research Resources:

Applicants should leverage existing research resources for their studies. An example of such an existing resource is the NINDS BioSEND or other existing biospecimen, imaging and data repositories. Leveraging the resources and support from advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program are also encouraged. Studies are also encouraged that leverage the resources of ongoing clinical trials supported through other Federal or private funds. Researchers may consider collecting data to validate new or improved COA measures or biomarkers as ancillary studies to ongoing clinical trials or longitudinal studies.

Applications Non-Responsive to this Funding Opportunity Announcement

  • Applications that propose animal studies will not be accepted for review.
  • Studies of biomarker discovery or early characterization should seek funding through the parent FOAs for research project grants.Studies of disease pathophysiology, genetic or epigenetic mechanisms are not responsive to this FOA.
  • Applications that request support for infrastructure to establish new clinical trial networks are not responsive to this FOA.
  • To be considered for support through this FOA, the biochemical or molecular biomarker analytical assay(s) should be already characterized in terms of accuracy, precision, analytical sensitivity and specificity, effects of interfering substances, dynamic range, and expected normal values. It is not the intent of this FOA to support studies of biomarker discovery or analytical validation.

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
Renewal
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?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

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

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

The maximum request cannot exceed 5 years but the actual funded project period is dependent on reaching specific milestones as described in this FOA.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Required Registrations

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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.

In addition, specific to this FOA: describe the access of proposed sites to FND populations and the availability of the necessary multidisciplinary expertise.

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.

In addition, specific to this FOA: describe the expertise of key personnel in FND care and research, and the ability of the team to cover the relevant breadth of multidisciplinary expertise.

R&R or Modular 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:

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

Stage of development and status of outcome measure or biomarker: The Significance section of the Research Strategy must include a paragraph clarifying what stage of development the instrument is in, and what additional validation steps are needed for use in clinical trials.

Include a description of the currently available COA measures, endpoints, and/or biomarkers. If appropriate for the proposed study, describe how the study will result in advancements over the currently available measures/biomarkers. Outline the unmet need that the proposed biomarkers and/or COAs will fill.

If biomarker validation is proposed, the approach section of the application must contain a subsection with the heading “Biomarkers and Their Contexts of Use”. This section should describe each biomarker that will be tested for validation and the context of use (COU). The COU should briefly explain how, when and why the biomarker is to be used.

Describe whether the proposed biomarker and/or COA is in use and/or has been validated in a related condition.

The application must address the feasibility of using the proposed biomarker and/or COA, and the likelihood that it will be broadly adopted by the health care community in diagnosis, treatment or prevention applications.

Provide the biological rationale for the biomarker or COA chosen.

Provide a rationale for the choice of biomarker or COA for the specific FND type or disease feature.

COA measures can be clinician-, observer-, or patient-reported, or performance outcomes. Applications must provide a list of all COA measure to be validated.

Describe a plan for minimizing bias and ensuring transparency regarding data collection.

Describe the plan for addressing any ethical concerns specific to FND populations.

Describe a plan for integrating input from the patient or care-giver community into the study design and future use plan.

Preliminary data: This section should identify the biomarker, endpoint, or COA to be studied and detection method, and summarize the available preliminary data supporting the choice of measure to be studied, its feasibility, the current validation status, and, if appropriate, the preliminary rationale for context of use. Preliminary data for the sensitivity, specificity, and other relevant characteristics should be included if available.

Statistical Analysis Plans: A section describing the plans for statistical analysis of the data and tests for validation of biomarkers/COA (s) must be included in the application. Explain the decision for selecting the statistical analysis methods and how the methods selected are best suited for this study—what methods were considered; why the proposed methods were chosen. Describe sample size considerations for validating the biomarkers, endpoints and COA(s). Describe the power analysis and a justification for the sample size, as well as plans for enrollment, retention, handling dropouts and missed data points.

Project Milestones and Timelines

In this subsection under Approach, applicants must describe milestones to be used for measuring success in achieving each of the research plan’s aims. Specify the quantitative criteria for measuring success and related rationale. One or more milestones should be used for each aim. Specify the timeline for each milestone. There should be at least one milestone each year. Consider including an interim data analysis and provide quantitative criteria for go/no-go decisions for continuing the study of each biomarker and/or COA. This is especially encouraged for any invasive biomarkers such as those involving longitudinal lumbar punctures.

Examples of milestones include, but are not limited to the following:

  • Go/no go decision points regarding biomarker and/or COA feasibility, precision, range, accuracy, sensitivity, specificity, reliability, responsiveness, and generalizability
  • Institutional Review Board (IRB) and other regulatory approvals (applicants are encouraged to use a central IRB)
  • Certification of clinical sites regarding the training of personnel on the study protocol, calibration of instruments, implementation of data management and safety monitoring protocols, etc.
  • Approval of the research protocol by the Advisory Committee
  • Patient enrollment (including gender, race and ethnicity, children) and clinic visit milestones for each grant year.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, are expected to include a plan for the sharing of clinical data and biospecimens, consistent with achieving the goals of the program.

This Data/Resource Sharing Plan should include a timeline for publications and access to additional study data and biospecimens. It should describe the process for evaluating requests for access to the data and/or biospecimens, and the expected time from when the request is received to when the sharing of data/biospecimens is achieved. If using BioSEND, briefly describe how this resource will be used to bank and distribute biospecimens. A table of the requests should be included in annual progress reports and provided to the Advisory Committee, including the requester's name, nature of the request, date received, description and date of follow-through on each request.

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.

The following appendix materials should be included:

  • Standardized protocols for measuring the biomarkers or evaluating the COA proposed are required (these are evaluation or measurement protocols, not study protocols)
  • If an ancillary study is proposed, the protocol for the parent clinical trial or longitudinal study and the consent form for the parent study are required
  • Where applicable, if the applicants have had communications with the FDA about the proposed biomarker(s) or COA measure(s), a summary of the meeting or documentation of guidance from the FDA is required.
  • If the proposed study involves the expanded access regulatory pathway, protocols used for expanded access studies or documentation submitted to FDA to initiate and amend expanded access protocols are required.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

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.

In addition, for applications involving clinical trials: 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.

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?

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 application identify the specific need in FND and the subtype of FND(s) targeted?
  • Is the choice of biomarker/COA justified for the specific FND manifestation targeted?
  • Is the COU for the proposed biomarker and/or COA clearly described?
  • Does the proposed biomarker/COA appear feasible and likely to be widely adopted for clinical applications?

 

 

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:

 

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 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:

  • Do the clinical sites have access to the needed numbers of patients with FND to support enrollment for the study?
  • How strong is the justification that all of the participating clinical sites have the appropriate expertise and equipment for measuring COAs and analyzing appropriate biomarkers?

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.

 

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.

 

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.

 

For Renewals, the committee will consider the progress made in the last funding period.

 

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) 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), 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 submitted in response to this FOA. 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.

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:

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigatorR#8217;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 OMB administrative guidelines, HHS 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, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH 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 recipients for 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:

defining of research objectives and approaches, planning, conducting, analyzing, and publishing results, interpretations, and conclusion of their studies and for providing overall scientific and administrative leadership for the Research Project.

Supervising of the clinical study with a consistent emphasis on collaborative interactions between investigators, advisory and steering committees, and NINDS representatives.

Recipientss will retain custody of and have primary rights to data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

NINDS staff involvement will include oversight of the IRB-approved protocol by the NINDS Program Official, documentation of adequate serious adverse event management and reporting, and regular communications with the principal investigator and staff; additional involvement generally includes participation in meetings of the steering committee and other leadership committees. Specifically:

An NINDS Project Scientist working with the network investigators will develop milestones for the study. Failure to meet the agreed-upon milestones may result in reduced funding or early termination of the cooperative agreement. The NINDS retains the option to obtain periodic external peer reviews of progress.

The NINDS Project Scientist will function as one of several co-investigators, collaborating and interacting as necessary with the Principal Investigators in accomplishing the overall goals of the Research Program.

In addition, an NINDS Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

A separate NINDS Program Official, from the Division of Clinical Research, will serve as the NINDS liaison to the Data and Safety Monitoring Board if it is determined that a DSMB is needed for the study.

If the proposed trial should require that FDA issue an IND, the NINDS Project Scientist and/or Program Official(s) will be present at any meetings held with the FDA related to this NIH-funded protocol.

As with any award, even during the period recommended for support, continuation is conditional upon satisfactory progress. If at any time, recruitment falls significantly below the projected milestones for recruitment, the NINDS will consider ending support and negotiating a phase-out of the award. The NINDS retains the option to obtain periodic external peer reviews of progress. Milestones will be established by the NINDS prior to the award of the grant based on recommendations from the primary review group. NINDs will make an award for 2 to 3 years in order to start up the trial and establish performance feasibility. Continuation of the award past this feasibility period will be contingent upon a demonstrated ability to meet milestones indicating that the trial can be implemented as planned. Feasibility milestones will be defined at the start of each trial and will be monitored closely by the Institute-appointed Data and Safety Monitoring Board (DSMB), if applicable, and NINDS Program Official. Achievement of these milestones will be evaluated by NINDS prior to releasing funding for each year of the award and failure to achieve these milestones may lead to study termination.

Areas of Joint Responsibility include:

None; all responsibilities are divided between recipients and NIH staff as described above.

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. It will have three members: 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 in no way affects the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D, and HHS regulations 45 CFR Part 16.

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: 301-945-7573

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

Scientific/Research Contact(s)

Codrin Lungu, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
E-mail: lunguci@ninds.nih.gov

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

Rebecca Hommer, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-2257
E-mail: rebecca.hommer@nih.gov

Peer Review Contact(s)

Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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

Authority and Regulations

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

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