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

NINDS Exploratory Clinical Trials (R01)

Activity Code

R01 Research Project Grant

Announcement Type

Reissue of PAR-10-199

Related Notices

  • March 3, 2014 - See Notice NOT-NS-14-016. Notice to Correct the NINDS CFDA number associated with this FOA.
  • January 16, 2014 - See Notice NOT-NS-14-007. Notice of Correction of NINDS's CFDA number.
  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number

PAR-13-281

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.853; 93.583

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to provide a vehicle for submitting grant applications for investigator-initiated exploratory clinical trials to the National Institute of Neurological Disorders and Stroke (NINDS).  The trials must address research questions related to the mission and goals of the NINDS and may evaluate drugs, biologics, devices, or surgical, behavioral or rehabilitation therapies.  Information about the mission, strategic plan and research interests of the NINDS can be found at the NINDS website (http://www.ninds.nih.gov/).  

Key Dates
Posted Date

July 23, 2013

Open Date (Earliest Submission Date)

September 5, 2013

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Standard dates apply, 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.

AIDS Application Due Date(s)

Standard AIDS dates apply, 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.

Scientific Merit Review

Standard dates apply

Advisory Council Review

Standard dates apply

Earliest Start Date

Standard dates apply

Expiration Date

September 8, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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


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Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description

The NINDS is committed to advancing treatments for people burdened by neurological diseases.  This FOA encourages applications for exploratory clinical trials including Phase 1 and 2 studies of drugs and biologics, feasibility studies of devices, as well as preliminary studies of surgical, behavioral or rehabilitation therapies, that contribute to the justification for, and provide some of the data required to, lead to a future trial to establish efficacy (such as a Phase 3 trial or a Pivotal device trial).  A wide range of trials at different stages of development are allowed, including first-in-human (as defined by the Food and Drug Administration), Phase 1 and 2 single-site studies, and Phase 2b multicenter studies.   Applications must aim to generate data that inform further clinical development of the proposed intervention.  The earliest studies should be designed to provide important initial information regarding the intervention (e.g., safety, tolerability, dosing).  Later-stage studies will generally include randomization and blinding and should yield data that allow a clear go/no-go decision regarding whether the intervention should proceed to an efficacy trial.  All applications must outline specific plans for future development in the event of promising results. 

Examples of appropriate studies under this FOA include, but are not limited to, those designed to:

NINDS recognizes that devices can differ greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc.  A Pivotal device study, for example, could potentially be used in support of an off-label indication of an existing market approved device, or to provide evidence for a novel device design in support of a Pre-Market Approval (PMA), Humanitarian Device Exemption (HDE), 510(k) or 510(k) De Novo submission.  Due to the broad scope of possible medical devices and the varied nature of the regulatory path, investigators considering applications to evaluate devices are strongly encouraged to contact Program Staff as early as possible to discuss these issues and determine the suitability of their project for this funding mechanism.

Applicants should take note of the following:

(1) NeuroNEXT: NINDS has a network called NeuroNEXT specifically designed to implement multi-site exploratory clinical trials (see http://www.neuronext.org/) and when appropriate, it is strongly preferred that such trials be performed within this network.  Therefore, before submitting a application l to this FOA, applicants should follow the instructions on the above website to obtain feedback on the suitability of their trial for NeuroNEXT.  An important advantage of NeuroNEXT is that it can provide clinical, statistical and logistical expertise in developing study protocols as well as a standing national network of experienced clinical sites prepared to enroll study participants.

(2) Efficacy: This FOA is not intended to support the conduct of a clinical trial where the primary aim is to establish or confirm definitive efficacy.  Applications to implement definitive efficacy trials (e.g., Phase 3 trials of drugs or Pivotal device trials) should be submitted to PAR-13-278 , NINDS Investigator-Initiated Phase 3 Clinical Trials.

(3) Effect Size: A trial will not be considered under this FOA when its primary objective is to estimate intervention effect size to be used in power calculations for a future efficacy clinical trial.  Effect size estimates based on small or short-term studies are often unreliable.  Power for an efficacy trial should be based on the smallest clinically meaningful effect size.

(4) Inclusion of Minorities and Women in Clinical Trials: NIH policy requires that women and minorities be included in clinical trials, unless it is not scientifically justifiable.  Applicants must include a plan to enroll women and minorities.  Considerations that may contribute to successful inclusion are: appropriate site-selection, patient or community-engagement for the major elements of the project, use of focus groups to address barriers to inclusion, etc.  As well, applicants should include a discussion of how the gender and minority findings will be reported to the NINDS.

(5) Secondary Aims: For drugs and biologics, issues of study feasibility and refinement of study procedures may be addressed as secondary aims in an exploratory clinical trial, but not as the primary aim.  Examples of such secondary aims include:

(6) Multiple Trials: There may be multiple questions remaining to be answered before a Phase 3 trial can be designed and conducted.  The proposed study is not required to address all potential questions but the applicant should clearly detail the total clinical development plan for the intervention.

(7) Exploratory IND/Early Feasibility studies: Applicants may propose Exploratory IND studies as defined by the FDA (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078933.pdf) or early feasibility studies of devices as defined by the FDA (http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm279103.pdf).

(8) Rationale: The rationale for an exploratory trial must be based on (1) an unmet medical need; (2) a plausible biological mechanism; (3) non-clinical (in vivo and/or in vitro data); and (4) preliminary clinical data.  Although all of these criteria may not be met, the applicant must demonstrate that there is an adequate scientific foundation to justify the proposed trial.  Applicants citing preclinical research should ensure it meets the high scientific rigor guidelines published by NINDS (see http://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html).  If research does not meet the criteria outlined to an acceptable degree, applicants should consider not including it as evidence in support of the trial rationale.  If the data are included, then the applicants should discuss the limitations.  Likewise, any prior clinical research cited should be scientifically rigorous. 

(9) Biomarkers:

(10) Adaptive Designs: The use of innovative and efficient study designs is encouraged, such as adaptive dose-finding designs, designs incorporating plans for sample size recalculation, and futility designs.  Applications for Phase 1 trials in the patient population are encouraged when appropriate, as are applications that encompass Phase 1 and Phase 2a studies (early proof of mechanism or proof of concept).  For a Phase 2 trial of a drug or biologic, specific plans for the next steps of the therapy's development (such as a future efficacy trial) must be succinctly stated.  Applications for seamless Phase 2/3 trials should be submitted under to PAR-13-278 , NINDS Investigator-Initiated Phase 3 Clinical Trials. For medical devices, Early Feasibility and Traditional Feasibility study designs may include single-arm case series, on-off interventions (patients as own controls), device-device comparisons, comparisons to historic controls, comparisons to performance controls, or adaptive/Bayesian designs.

(11) Simulations: Computer simulations are sometimes used to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs), to choose between alternative outcome measures, or to determine sample size, by taking into account the impact of noncompliance, missing data, and subject eligibility criteria, etc. 

(12) Pharmacometrics: Applications seeking to obtain data needed for pharmacometric modeling are encouraged, with the ultimate aim of enabling the optimal design of a future efficacy trial of an intervention. 

(13) Rare Diseases: Trials in rare diseases are encouraged, and it is recognized that available patient pools may not be adequate to meet the sample size requirements typically seen in Phase 3 trials.  Innovative trial designs, including crossover designs and adaptive designs, may allow for the most efficient evaluation of the limited subjects available for study.  For trials in rare diseases, it is especially important to ensure that the study design will meet the stated objectives, and the approach should carefully be justified.  Applicants proposing Phase 3 studies aiming to demonstrate evidence of efficacy to support a licensing application are encouraged to contact the FDA to gain concurrence on the trial design.  Applicants are also advised to contact NINDS program staff early in the planning process.

(14) 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. 

(15) Regulatory Approvals: As per NINDS policy (http://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-018.html), at the time of grant submission, if the intervention is a drug, biologic, or device, applicants must provide documentation from the FDA providing information on one of the following three scenarios:

(a) The protocol has been submitted under an open IND/IDE and the IND/IDE is not under full or partial hold.  Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.

(b) The protocol has been submitted under an IND/IDE and is on full or partial hold.  Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations.

(c) The protocol is exempt from an IND/IDE.  Under this scenario applicants must provide a copy of the exemption letter from the FDA.

Applications that do not include this information will be withdrawn and not reviewed.  Prior to grant award, awardees who do not have an exemption from the FDA must provide any additional FDA correspondence regarding the status of the protocol to the NINDS, especially if the trial has been placed under full or partial hold.

IRB approval is not required at the time of application submission, but is required prior to funding.  As such, 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. 

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

(a) Clinical and Translational Science Award (CTSA) program (https://www.ctsacentral.org);

(b) NeuroQOL (http://www.neuroqol.org);

(c) NIH Toolbox (http://www.nihtoolbox.org);

(d) PROMIS (http://www.nihpromis.org); and

(e) NINDS Common Data Elements (http://www.commondataelements.ninds.nih.gov).

(17) Mobile Technologies: Applicants are encouraged to consider utilizing (at least experimentally) mobile technologies to facilitate data collection and protocol adherence on the part of research participants and study site staff.

(18) Consultation with NINDS: Applicants are encouraged to consult with NINDS staff in the Office of Clinical Research as plans for an application are being 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.  As well, discussions regarding strategies for recruitment and inclusion of women and minorities are available.

Section II. Award Information
Funding Instrument

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

Application Types Allowed

New
Renewal
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

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 scope of the proposed project should determine the project period. The maximum period is 5 years.  

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

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

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.

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

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information


1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

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

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed. Projects with very long titles (i.e., more than 80 characters with tag) should use only an acronym plus the appropriate tag, and the full title should be spelled out in the abstract.

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, with the following additional instructions:

(a) The protocol has been submitted under an open IND/IDE and the IND/IDE is not under full or partial hold.  Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.

(b) The protocol has been submitted under an IND/IDE and is on full or partial hold.  Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations.

(c) The protocol is exempt from an IND/IDE.  Under this scenario applicants must provide a copy of the exemption letter from the FDA.

Applications that do not include this information will be withdrawn and not reviewed.  Prior to grant award, awardees who do not have an exemption from the FDA must provide any additional FDA correspondence regarding the status of the protocol to the NINDS, especially if the trial has been placed under full or partial hold.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed. The clinical trial must be directed by an investigator with experience in the conduct of clinical trials and expertise in the disease area. Such experience must be documented, including timely submission of primary publications from previous trials, ideally within one year of completion of subject follow-up.  The application also should indicate the prior experience of study team members in clinical trial design and implementation. Biographical sketches for all key personnel must be provided.

R&R or Modular Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: The specific aims of the exploratory clinical trial must be clearly and concisely presented.  The primary and major secondary hypotheses to be evaluated must be clearly stated.

Research Strategy:

Significance and Biological Relevance:

The significance and, when applicable, the biological relevance of the proposed clinical trial must be clearly stated.  It is particularly important that there be discussion of how the trial will test the primary hypothesis and how the results of the trial (positive or negative) will advance the field.  The application should explain why the proposed trial is necessary to plan for subsequent studies.

Prior Studies and Rationale for Development:

The major findings of the preclinical and clinical studies that led to the proposed clinical trial should be described according to the previously mentioned NINDS guidelines for rigor (see http://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html).  Pilot studies that show the need for and the feasibility of the trial should also be discussed.  Study conceptualization and planning must be at a stage sufficient to allow for an assessment of the likelihood of trial success.

Applications should address the reasons for consideration of the intervention.  This may include preclinical in-vitro and in-vivo data.  Animal efficacy data should be included in the rationale only when the model and read-out are considered sufficiently associated with the human condition, and only if the experiments sufficiently meet criteria outlined in the aforementioned NINDS guidelines.  Other considerations are toxicology data (e.g., whether the FDA has found the toxicology data to be acceptable to proceed with the proposed trial); medicinal chemistry/pharmacology data (e.g., whether the formulation is feasible and the pharmacokinetics acceptable for use as intended in the trial); regulatory considerations (e.g., details on FDA, European Medicines Agency (EMA), and other agencies’ evaluations; discussion of the likelihood of regulatory approval based on acceptability of endpoints, orphan drug status, etc.); public health impact if subsequent efficacy trials are conducted and positive; ethical dimensions; and patient perspectives on acceptability of the proposed intervention. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so that peer review may evaluate the strength of the supporting evidence (see http://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html and http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf).  If preclinical data (e.g., animal studies) do not meet the rigor guidelines, the applicant should discuss the limitations of those data.

Study Design:

A summary of the trial protocol should be presented in the Research strategy and must include the items listed below. 

As part of the Research Strategy, the application must include:

Human Subjects: NIH’s policy requiring education on the protection of human research participants must be followed for all key personnel (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html).

Applicants should refer to Part II of the SF424 Application Guide, “Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan” (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerB.pdf).

Assurance of the protection of human participants and the biohazard safety of employees (if applicable) must be provided for the overall study and for each clinical site.  The applicant must discuss any issues which might lead to concern for the welfare of participants.  Additionally, the human subjects section of the application must address data security measures and confidentiality.  

Data and Safety Monitoring Plan: Applicants must include a Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical trial (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html). The DSM Plan should be included in the study protocol and must provide a general description of the monitoring plan, policies, procedures, responsible parties, and procedures for identifying, managing and reporting “reportable events” (i.e., serious adverse events and unanticipated problems) to the applicable regulatory agencies [e.g., Institutional Review Boards (IRBs), the NINDS, the NIH Office of Biotechnology Activities, the Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA), and the Data and Safety Monitoring Board (DSMB) or other study monitoring authority].  Therefore, the DSM Plan must address the following areas:

For exploratory clinical trials it generally will be acceptable for the data and safety monitoring to be conducted by an investigator-appointed Study Monitoring Committee (SMC), an Independent Medical Monitor (IMM), or, for single-site trials involving low risk, the Program Director/Principal Investigator and his/her IRB.  However, NINDS may decide to establish an independent Data and Safety Monitoring Board (DSMB) depending on the score and risk of the trial.  Applicants should refer to NIH’s policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html) as well as the NINDS Guidelines for Data and Safety Monitoring (http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm). 

Letters of Support:

Applicants are encouraged to include letters from patient organizations or other supporting documentation to show that patients were included as partners in the concept development and design of the trial.

Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants as well as service agreements for personnel or facilities.  Letters of commitment must be co-signed by the business official of the collaborating center.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Investigators are expected to include a brief one-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see the NIH Data Sharing Policy, http://grants.nih.gov/grants/policy/data_sharing/).

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modifications:

The following additional documents must be included in the Appendix material of the CCC application in the order listed below:

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. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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 by the Center for Scientific Review, NIH. Applications that are incomplete 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 for the entire cluster of components for the trial (e.g., CCC, DCC, etc.) for any year (excluding consortium F&A) must contact NIH program staff as early as possible but 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 NOT-OD-10-115.

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Applications will be evaluated from two perspectives: the scientific rationale/premise of the study and the study design as outlined in detail below.  Where applicable, preclinical data used to support the rationale for the study will be evaluated for scientific rigor of the experimental design, for the strategies used to minimize bias, for the robustness and reproducibility of the reported results and for consideration of alternative interpretations.  The scientific review also will focus on the overall impact of the study and will include the evaluation of the experimental design and all of the review criteria described below.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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? 

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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 there evidence that the primary results of prior trials have been submitted within one year of data base lock?   

Innovation

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

Does the proposed trial have the potential to advance the field (e.g., by elucidating critical aspects of the pathogenesis of the disease or by breaking ground for future trials in this area) even if (a) the proposed study design, methods, and intervention are not innovative, and/or (b) the results of the trial indicate that further clinical development of the intervention is unwarranted? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

Is there adequate consultation with patients and other stakeholders in study design (e.g., inclusion of a patient representative on the Steering Committee)?If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  

Additional Review Criteria

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

FOA-Specific Review Criteria

Clinical Trial Documentation (Study protocol, Clinical Investigator's Brochure or equivalent, etc.)

Plans for Patient Recruitment/Retention

Does the application document the following?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

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

Renewals

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

Revisions

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

Additional Review Considerations

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

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

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

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Neurological Disorders and Stroke, 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:

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 National Advisory Neurological Disorders and Stroke Council. The following will be considered in making funding decisions:

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

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.      

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Peter R. Gilbert, Sc.M.
National Institute of Neurological Disorders and Stroke
Telephone: 301-496-0870
Email: ExploratoryTrial@ninds.nih.gov

Peer Review Contact(s)

Chief, 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)

Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@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 Parts 74 and 92.


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