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

Centers Without Walls for Collaborative Research in the Epilepsies: Functional Evaluation of Human Genetic Variants (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-NS-18-001

Companion Funding Opportunity

None

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

93.853

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage cooperative agreement (U54) applications from multidisciplinary groups of investigators to accelerate the rate of progress in determining the functional, pharmacological, neuronal network and whole animal consequences of genetic variants discovered in patients with various types of epilepsy and to develop strategies for establishing diagnostic criteria and identifying potential targets for intervention.

Key Dates

 

Posted Date

September 7, 2017

Open Date (Earliest Submission Date)

New Date December 16, 2017

Letter of Intent Due Date(s)

October 15, 2017

Application Due Date(s)

New Date January 16, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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)

Not applicable

Scientific Merit Review

New Date June 2018

Advisory Council Review

New Date August 2018

Earliest Start Date

New Date September 2018

Expiration Date

New Date January 17, 2018 per issuance of NOT-NS-18-010. (Original Expiration Date: November 16, 2017)

Due Dates for E.O. 12372

Not Applicable

** ELECTRONIC APPLICATION SUBMISSION REQUIRED**

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Learn more about the various submission options.

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

Overview

The goal of this Epilepsy Center without Walls (CWOW) is to improve understanding of the functional consequences of genetic variants and accelerate progress in translating genomics to allow biologically based diagnoses, individualized treatments and target identification for the development of novel therapeutic agents. The CWOW award will support studies of the functional, pharmacological, neuronal network activity and whole animal consequences of causal and putatively causal genetic variants, generation of key resources (e.g., animal models, induced Pluripotent Stem Cells (iPSCs) for assessment of these variants, and development of strategies to classify variants as treatment targets and establish diagnostic criteria.

Background

The NINDS supports research to understand, treat, and ultimately prevent the diverse collection of epilepsies and seizure-related syndromes. These disorders have a wide range of severities, precipitating causes, comorbidities, and treatment outcomes. In many cases, it is believed that genetic factors play a role in the risk and causes of some seizure-related disorders and a number of the epilepsies.

The first NINDS CWOW funding opportunity announcement (FOA) supported discovery of genes involved in human epilepsies. From this FOA, the Epi4K consortium was funded in September 2011 to study the genetics of the epileptic encephalopathies, malformations of cortical development, genetic/idiopathic generalized epilepsy and non-acquired focal epilepsy. Several months earlier in March 2011, the EuroEPINOMICS Rare Epilepsy Syndromes (RES) human genetics effort was launched for a three year period. These and other efforts have revealed variants in known and novel genes that were statistically identified as causal through whole exome sequencing. It also became clear that numerous additional genes could be implicated if sample sizes were larger. For example, the recently published Deciphering Developmental Disorders study searched for de novo mutations and implicated 27 new epilepsy genes from the Epi4K epileptic encephalopathies study. Moreover, the epilepsies were included in one of the NHGRI Genetics of Common Diseases funded efforts, such that thousands of additional patients with epilepsy will be sequenced in the near future. It is expected this will lead to identification of many more genetic variants and allow for identification of potential drug targets.

Genetic influences on the development of epilepsy or seizure-related disorders may be monogenic or polygenic, and may also involve environmental factors. Of those genetic factors that have been discovered thus far, mutations in ion channels, synaptic proteins and neurotransmitter receptors appear to play a prominent role. Progress has been made in identifying genetic causes for selected Mendelian disorders (e.g. Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE), Autosomal Dominant Partial Epilepsy with Auditory Features, familial Genetic Generalized Epilepsy (GGE) and Non-Acquired Focal Epilepsy (NAFE)) and for mutations and copy number variants that arise de novo (Epileptic Encephalopathies).

Scope

Specific Research Objectives

This FOA solicits applications from multidisciplinary groups who wish to study the functional, pharmacological, neuronal network and whole animal consequences of variants identified as causal or potentially causal, to identify and test molecular targets for intervention, and to establish diagnostic criteria. In addition, it is expected the results obtained and research platforms developed will be disseminated through publications, ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), and cell (https://nindsgenetics.org/ or http://rucdr.org/) and animal (Mutant Mouse Resource and Research Centers or Jackson Laboratory) repositories.

Specific Areas of Research Interest

U54 applications must include for at least two scientific projects and at least one core in addition to the administrative core to study epilepsy genetic variants, to identify potential treatment targets through categorization of variants according to function, pathways or by other means, and to establish diagnostic criteria. Examples of possible project/core support include but are not limited to administrative, iPSC, functional and pharmacological evaluation, animal models, target identification and diagnostics. Other projects/cores may be proposed if appropriate to the goals of the proposed CWOW.

A partial list of specific areas of interest include:

  • Assessment of genetic variants identified in ion channels, synaptic proteins, signaling pathways, transcription factors or enzymes
  • Introduction of variants to human induced pluripotent stem cells
  • Pharmacological evaluation of causal and candidate variants
  • Evaluation of network activity from differentiated human iPSCs or animal models
  • Development and characterization of high priority animal models
  • Establishment of ClinVar standardized data elements for epilepsy genetic variants
  • Identification of potential drug targets
  • Establishment of diagnostic criteria
  • Detection of epigenetic effects

As the research strategy is prepared, it is important to note that NINDS believes applications will be greatly strengthened if the design, execution, and interpretation of the proposed studies and supporting data are adequately described. NINDS encourages investigators, whenever possible, to address these elements directly in their applications. Investigators are urged to discuss these issues with Scientific/Research staff prior to submission of applications (see: NOT-NS-11-023 and NOT-OD-15-103). The NINDS also expects that applications for the Epilepsy CWOW will conform to the principles outlined in Landis et al., 2012 and show consideration for the epilepsy-specific issues described in Simonato et al., 2014 and other biological variables described in NOT-OD-15-102.

Activities that are not responsive to this FOA:

1) Translational activities: Applicants should note that translational activities such as those supported in the NINDS Blueprint Neurotherapeutics (BPN), CREATE Bio or Create Devices programs should not be included in the CWOW application. These activities include large-scale medicinal chemistry/lead optimization programs, extensive PK/PD experiments, and IND-enabling studies (such as scale up, manufacture, and GLP toxicology studies). Human studies using a device intervention will not be allowed. Please see NINDS Division of Translational Research for full descriptions of appropriate translational developmental programs. Applicants are encouraged to contact program staff to better understand the scope of preparatory studies that may be proposed in the CWOW application, and studies that should be pursued subsequently in the full-scale translational programs.

2) Clinical trials, as defined by the NIH. Applicants who wish to propose clinical trials should review Clinical Research for NINDS clinical trial FOAs. Phase II clinical studies can be submitted to NeuroNEXT).

3) Patient recruitment for gathering bio-specimens (e.g. fibroblasts from skin biopsies) is out of scope.

4) Establishment of repositories for brain and related bio-specimens is not responsive to this FOA, as described in NOT-MH-12-020. If iPSC lines need to be banked and distributed, this can be done through the NINDS Human Cell and Data Repository (https://nindsgenetics.org/ or http://rucdr.org/).

Required components:

Each CWOW application must have an Administrative Core, at least two Research Projects and at least one Research Core. The research projects and cores should reflect the overall theme(s) and requirements of the CWOW to achieve its goals and should be appropriate for the requested budget.

The Epilepsy CWOW is a collaborative effort that requires frequent interactions of awardees among themselves and with the NIH. Applicants should be willing to: participate in Executive and/or Steering Committee Meetings and regular telephone conference calls; cooperate with other awardees in the development and design of research priorities, especially regarding resources; and agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2. "Award Administration Information.

Milestones: Each component should include a set of annual quantifiable milestones as benchmarks to judge overall progress.

Administrative Core: The Program Director(s)/Principal Investigators (PD/PIs) should serve as the lead(s) of this Core. The Administrative Core should provide for the integration and management of activities within the CWOW including:

  • Provide leadership and expertise

Work with NINDS staff to establish annual milestones

  • Provide reports to NINDS on all issues related to individual project and subcontract site performance.
  • Schedule and provide logistical support for site meetings and teleconferences. The administrative core should plan to organize an in-person meeting of the Steering Committee at least one time per year. An all-site meeting for the Center without Walls should occur at least once a year. A Steering Committee conference call should occur at a minimum once a month and should be a component of the Center operations. The administrative core should provide minutes of all calls and meetings to the NINDS.
  • Track publications from the center and assist in preparation of collaborative presentations, manuscripts and progress reports.
  • Make raw and analyzed data available to Center investigators and to publicly available databases (e.g. ClinVar) as specified in the data sharing plan.

Ensure dissemination of iPSCs or stable cell lines by depositing cells at the NINDS Human Cell and Data Repository (https://nindsgenetics.org/ or http://rucdr.org/).

Maintain a public website to communicate the mission and goals of the CWOW. This website should also advertise the availability of data, reagents, methods and other resources to the rest of the community, since an important goal of the CWOW program is to share resources with the broader epilepsy research community.

Research Cores and Research Projects

Any combination of at least two research projects and at least one research core can be used to address the list of research areas of interest plus other relevant research areas. Each Core and Project should include annual milestones, which are goals that are quantifiable for measuring success of the Research Project or Research Core (see Section IV.2 for details).

In addition, if preclinical models have been developed, optimized or validated in the CWOW activities, awardees will be expected to work with the NINDS Epilepsy Therapy Screening Program (ETSP) to consider whether and how such models could be incorporated into the NINDS ETSP.

Pre-application Consultation

As an U54 cooperative agreement, implementation will involve the participation of NINDS program staff in the planning and execution of the CWOW.  Applicants are strongly encouraged to consult with NINDS Scientific/Research staff when planning an application. Early contact provides an opportunity for NINDS Scientific/Research staff to provide further guidance on program scope, goals, and developing appropriate milestones. Applicants should contact NINDS Scientific/Research staff at least 8 weeks before the receipt date.

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

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

Funds Available and Anticipated Number of Awards

NINDS intends to commit $3,000,000 direct costs in FY 2018 to fund up to two awards at $1,500,000 direct costs each.

Award Budget

Application budgets are limited to $1,500,000 direct costs per year.

Award Project Period

 The scope of the proposed CWOW should determine the project period. The maximum project 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

  • 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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   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)

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)
  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not 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) (formerly CCR) – 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.
  • o   NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Randall R. Stewart, PhD
Telephone: 301-496-1917
Fax: 301-402-1501
Email: stewartr@ninds.nih.gov

Page Limitations

Component Types Available in ASSIST

Research Strategy/Program Plan Page Limits

Overall

12

Admin Core

12

Core

6

Project

12

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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

  • Overall: required
  • Administrative Core: required; maximum of 1
  • Research Core: at least one required
  • Research Project: minimum 2
Overall Component

When preparing your application in ASSIST, use Component Type ‘Overall’.

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

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement  (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Location(s) (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research & Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.  

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims:  The specific aims should briefly but specifically describe the goals of the proposed CWOW and summarize the expected outcomes, including the impact the proposed research will exert on the field.  

Research Strategy:  The Overall Research Strategy should describe the CWOW's goals and objectives, background information and the overall importance of the epilepsy genetic variants to be assessed. Describe the rationale for the proposed program. Explain the strategy for achieving the goals defined for the overall CWOW and how each research project and core relates to that strategy. A successful CWOW application will include a well-integrated research strategy that clearly demonstrates how genetic variants will be tested, information will be made available to the research community, how diagnostic criteria will be established and therapeutic targets identified. The CWOW should be viewed as interrelated Research Projects and Research Cores, each of which is not only individually scientifically rigorous but is complementary to the other Research Projects and Research Cores.

Describe the organizational structure of the CWOW. Also describe any connections between the proposed CWOW and any other organizations such as voluntary groups or industry partners. Explain how different units of the organization, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how combined resources create capabilities that are more than the sum of the parts.

Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants. Letters of support for the U54 CWOW overall should be included with the Overall component. Letters of support for individual scientific projects or cores should be included with those components of the application.

Collaboration with NIH Intramural Researchers: A letter from the Scientific Director of the collaborating NIH Institute or Center must be submitted as part of the CWOW application, and must specify the amount of intramural resources to be allocated to the proposed project. In addition, the letter should state that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research (if applicable).

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, with the following modification:

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

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.   

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application in ASSIST, use Component Type ‘Admin Core.’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project
  • Proposed Project Start/Ending Dates
PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)
  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   
Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Specific Aims: Describe the goals, expected outcomes and milestones for the Administrative Core

Research Strategy:   The Administrative Core should describe how it will 1) provide leadership and expertise in the design of a charter for the Center and common protocols for variant functional evaluation, cores and projects. If appropriate, use of NINDS Common Data Elements is strongly encouraged. 2) provide reports to NINDS and relevant oversight committees on all issues related to individual project and subcontract site performance. 3) schedule and provide logistical support for site meetings and teleconferences. 4) organize annual in-person meeting of the Steering Committee.  An all-site meeting for the CWOW should occur at least once a year. A Steering Committee conference call should occur at a minimum once a month and should be a component of CWOW operations. 5) provide minutes of all calls and meetings to the NINDS. 6) track publications from the CWOW and assist in preparation of collaborative presentations, manuscripts and progress reports. 7) include information on an agreed-upon charter for the CWOW and rules for authorship and ownership of data. 8) ensure that resources (iPSCs, stable cell lines, mice, etc.) are advertised through the CWOW's web-site and made available to the research community.

Letters of Support: Letters of support specific to the Administrative Core should be submitted.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The Administrative Core should provide oversight of the resource sharing plans of the CWOW. A sharing plan is expected to address the timely sharing of specimens, cells, animal models and de-identified data generated with support from this award with other qualified research scientists, both within and outside the CWOW, and ensuring that such data are HIPAA compliant, consistent with achieving the goals of this program. Applicants should describe plans for tracking requests for resources and monitoring the timely accomplishment of the activities described in the resource sharing plans. In addition, awardees should plan to explore ways in which preclinical disease modification or prevention models with demonstrated utility in the CWOW could be transitioned for use in the NINDS Epilepsy Therapy Screening Program (https://www.ninds.nih.gov/Current-Research/Focus-Research/Focus-Epilepsy/ETSP).

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.   

PHS Inclusion Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.  

 
Research Project

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant’s Project

Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Project)

In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Research Project)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)

Specific Aims: Provide a description of the goals, expected outcomes and milestones for the Project.

Research Strategy: Describe the research strategy for the Project. A Research Project should address the following questions. What are the functional consequences of causal and candidate human genetic variants? How do these functional changes affect brain function? What diagnostic criteria are useful for clinicians and patients? What pharmacological agents might be useful as candidate drugs? What combinations of animal models, cell-based assays and biophysical parameters provide a clear picture of the functional changes produced by causal genetic variants?

Cite published experimental details. Clearly describe the project's objectives and explain its relevance to the overall CWOW's theme. Specify the significance of the work proposed. As part of the Research Strategy, include information on preliminary studies, data, and/or prior experience pertinent to this application.

Describe the Research Project's use of Core services, including why the services are needed and the advantages and cost effectiveness of Core usage for the Project.

For off-site projects, justification should be provided for the project's location, and plans for interaction and cooperation with the other components of the CWOW should be addressed.

Milestones: Milestones are goals that are quantifiable for measuring success of the Research Project, and should have quantitative criteria associated with them.

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.

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.   

PHS Inclusion Enrollment Report (Research Project)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.  

Research Core

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (Research Core)

Complete only the following fields:

Applicant Information

Type of Applicant (optional)

Descriptive Title of Applicant’s Project

Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Core)

In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Research Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Core)

Not applicable

Specific Aims: Describe the goals, expected outcomes and milestones for the Research Core. 

Research Strategy: Describe essential Core functions and how the functions will contribute to and enhance the variant assessment effort, the determination of diagnostic criteria or the identification of therapeutic targets.

Staffing: Brief description of scientific, technical, and support staff.

Resources: Without repeating information provided on Facilities & Other Resources, provide a description of how Research Core resources will contribute to the goals of the Research Projects.

Services provided: Description of current and projected services to other Core and Research Components, as well as the process for prioritizing requests for use of Core facilities by the various Research Projects. If a Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant developments. 

Management: Description of overall management of the Core, decision-making process for use of Core services, and plans for cost-effectiveness and quality control.

Utilization of Core: Provide a summary of past and/or projected usage of Core services (e.g., assays performed, animals supplied, etc.). Include estimates of the percentage use of each Core unit by the affiliated Research Project components.

Milestones: Milestones are goals that are quantifiable for measuring success of the Research Core, and should have quantitative criteria associated with them.

A Core proposing to disseminate induced pluripotent stem cell (iPSC) lines or related resources can do so through the NINDS Human Cell and Data Repository (https://nindsgenetics.org/ or http://rucdr.org/).

Letters of Support: Include Letters of Support specific to the Research Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans, with the following modification:

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

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.  

PHS Inclusion Enrollment Report (Research Core)

Not applicable

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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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.

In order to expedite review, applicants are requested to notify the National Institute of Neurological Disorder and Stroke Referral Office by email at nindsreview.nih.gov@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

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

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.

Overall Impact - Overall

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CWOW 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 CWOW proposed).

Scored Review Criteria - Overall

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 CWOW that by its nature is not innovative may be essential to advance a field.

Significance

Does the CWOW address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the CWOW 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?

For this particular announcement, note the following:

What is the added value to scientific knowledge, technical capability, and/or clinical practice of the CWOW considered as a whole compared to the separate impact of the individual projects? How important is the CWOW structure to the prospects for success of the individual projects?  

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the CWOW? 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?

For this particular announcement, note the following: Does the CWOW PD/PI have the appropriate scientific and administrative qualifications and leadership ability to direct this CWOW? Is his/her commitment to the CWOW adequate to ensure its success? Have the CWOW PD(s)/PI(s) devoted sufficient effort to accomplish the goals of the CWOW? Do the investigators on the separate projects and cores show evidence of collaborating to advance the goals of the overall CWOW?

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?

For this particular announcement, note the following: How much does combining the different cores and subprojects into a single overall CWOW enhance innovation or increase the originality of the proposed work?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the CWOW? 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 CWOW 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 children, justified in terms of the scientific goals and research strategy proposed?  

For this particular announcement, note the following: Is there thematic cohesion to the CWOW? Is the interrelationship of individual projects and cores clear and scientifically well-justified? How will the administrative structure of the CWOW, including any advisory committees, contribute to its probability of success? Does the application clearly describe and justify the proposed administrative and organizational structure? Is the proposed structure adequate to support and encourage optimal interactions and collaboration among participants of the overall research effort? Does the administrative plan provide for internal quality control of ongoing research, management of day-to-day CWOW activities and for fair and effective communication and cooperation among CWOW members including resolution of disputes and allocation of funds? What are the overall quality of the projects and the adequacy of the services provided by the Research Cores?

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?

For this particular announcement, note the following: Is there evidence of sufficient institutional support for the CWOW? Does the environment encourage collaborative work among the CWOW investigators?

Additional Review Criteria - Overall

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.

Synergy: CWOW as an Integrated Effort

The overall U54 CWOW will be evaluated as an integrated research effort. The relationship and contributions of the Research Projects and Cores to the overall objectives will be discussed and evaluated. While it is highly desirable to have the research proposed in Individual Projects directly inform the conduct or interpretation of other CWOW projects, this is not a necessity as long as the proposed Projects are necessary to collectively inform the overall goal of the proposed CWOW.

Milestones:

Are milestones in Research Projects robust and associated with clear, quantitative criteria for success? Will the Overall CWOW milestones provide adequate information to evaluate annual progress of the CWOW as a whole?

Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?

Are there additional key experiments that need to have milestones?

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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed CWOW 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 children to determine if it is justified in terms of the scientific goals and research strategy proposed.  For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not applicable

Renewals

Not applicable

Revisions

Not applicable

Additional Review Considerations - Overall

As applicable for the CWOW 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

Not applicable

Select Agent Research

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

Resource Sharing Plans

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


Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

Review Criteria for Administrative Core

Reviewers will assign an impact score for the administrative core. The following review criteria will be used for the evaluation of the Administrative Core: Is there a clear, detailed plan for managing the CWOW's research and administration, ensuring appropriate prioritization of research, needed course corrections and problem identification and resolution, and effective sharing of resources, that conveys a high likelihood of effective, productive management of the CWOW as whole?

Are the core personnel qualified and experienced in the administration of a large, multi-component research program?

Is there an organizational structure that will facilitate collaboration, coordination, integration and timely evaluation of activities and progress?

Are there innovative features in the organizational design and decision making process?

Additional Review Criteria- Administrative Core

As applicable for the 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.

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 CWOW 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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Additional Review Considerations - Administrative Core

As applicable for the CWOW 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

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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


Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

Scored Review Criteria - Research Projects

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. The overall impact score will take into consideration: the scored review criteria and any specified additional review criteria; the extent to which the individual project enhances the strength of the overall CWOW, and the importance of the individual project to the success of the CWOW.

Significance

Does the Project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 Director(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)? Do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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?

Approach

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

As applicable for the 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.

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 CWOW 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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Additional Review Considerations - Research Projects

As applicable for the CWOW 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

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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


Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

Review Criteria-Research Core(s)

Each Research Core should provide essential functions or services to one or more projects. Reviewers will assign an impact score for core unit components. The following review criteria will be used for the evaluation of the individual Cores:

Is the proposed Research Core well matched to the needs of the overall CWOW? Does it provide essential facilities or services for one or more research projects?

What is the overall quality of the proposed core services? Are adequate quality control processes proposed for the facilities or services provided by the Research Core (including procedures, techniques, and quality control)? What are the criteria for prioritization and usage of Research Core products and/or services?

Are the qualifications, experience, and commitment of the leader of the Research Core and other key personnel adequate and appropriate for providing the proposed facilities or services?

Will the proposed Research Core provide cost effective services to the CWOW?

Is the environment for the Research Core adequate to support the CWOW as proposed?

Additional Review Criteria- Research Core(s) (if applicable)

As applicable for the proposed research core, 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.

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 CWOW 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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Additional Review Considerations - Research Core(s)

As applicable for the CWOW 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

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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


Authentication of Key Biological and/or Chemical Resources

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

  • 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.
  • Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines 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 National Advisory Neurological Disorders and Stroke Council. 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 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 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.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for the UDN will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below. Awardee will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

  • the overall functioning of the CWOW;
  • defining objectives and approaches, and for planning, conducting, analyzing, interpreting, publishing and sharing results;
  • developing and following the CWOW charter;
  • developing and proposing rigorous milestones that will be achieved during the project period;
  • providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NIH program staff request raw data, awardees agree to provide the data;
  • and promoting collaborative interactions between all Center investigators, steering committee, and NINDS representatives.

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

The NINDS Project Scientist will work closely with the PD/PI, the Steering Committee, and the PIs of all projects/cores in order to ensure proper conduct of the CWOW. The NINDS Project Scientist will be responsible for: (1) overseeing the activities of the CWOW, along with the other entities delineated above, to ensure that studies are properly conducted and completed in a timely fashion; (2) providing advice and guidance to ensure that the CWOW runs in accordance with NINDS policies and procedures, and is consistent with the mission of the NINDS to improve public health; (3) serving as a point of contact for investigators with the NINDS; and (4) disseminating information from the Institute and communicating with Institute leadership to ensure that the Center operates smoothly.

Milestones: Milestones are goals that are quantifiable for measuring success of each Research Project or Research Core, and should have quantitative criteria associated with them (see Section IV.2 for details). Milestones should also be included for each of the Overall CWOW Specific Aims, and should inform annual evaluations of progress of the CWOW as a whole.

Prior to funding an application, the NINDS Project Scientist will contact the applicant to discuss the proposed milestones and any concerns raised by the NINDS review panel or NINDS program staff.  A final set of NINDS-approved milestones will be specified prior to award.

Progress towards achievement of the final set of milestones will be evaluated by the NINDS Project Scientist and program staff.  NINDS program staff may consult with independent experts as necessary. If justified, future milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a project does not meet the milestones, funding for the project may be reduced or discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall progress, NINDS portfolio balance and program priorities, competitive landscape, and availability of funds.

Areas of Joint Responsibility include:

• None: all responsibilities are divided between awardees 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50,Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Scientific/Research Contact(s)

Randall R Stewart, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917
Email: stewartr@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, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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

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