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; 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 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.

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

Overview

The goal of this Epilepsy Center Without Walls (CWOW) is to accelerate development of transformative disease modifying or prevention therapies for epilepsy. The CWOW award will support preclinical and clinical "readiness" studies necessary prior to launching proposed therapeutic agents, devices or approaches into full-scale development (for example, with funding support from the NINDS Blueprint Neurotherapeutics Program or an industry partner). It is expected that the CWOW will enable applicants to create a highly synergistic environment in which preclinical and clinical investigators can iteratively work together - informing each other's studies - to develop the robust evidence needed to move one or more disease modifying or prevention therapies into the therapeutic development pipeline, and to prepare for future definitive clinical trials of safety and efficacy. A required public engagement core will support two-way communication among investigators and individuals representing the interventional population of interest. It is also expected that data, specimens and reagents developed in the CWOW will be shared in a timely way with investigators outside the CWOW as appropriate.

Background

The epilepsies are a collection of disorders that present significant public health burdens (see Epilepsy Across the Spectrum: Promoting Health and Understanding). The NINDS supports research to better understand, treat, and ultimately prevent the numerous seizure-related syndromes known as the epilepsies, as well as co-occurring conditions and early mortality. Although seizures can be controlled by available therapies for approximately two-thirds of people diagnosed with epilepsy, to date, surgery is the only intervention that definitively alters the course of the disease. There are no effective prevention therapies for individuals at risk. Two of the highest priorities identified by the epilepsy research community in the NINDS Benchmarks for Epilepsy Research are 1) the ability to modify the course of the disease in people with epilepsy, and 2) to prevent the development of epilepsy in those individuals who are known to be at risk, prior to the emergence of clinical or electrographic seizures.

Epileptogenesis, the development and extension of tissue capable of generating spontaneous seizures, contributes to both the initial clinical onset and the progression of epilepsy. Epilepsy prevention (preventing the first spontaneous seizure) and disease modification (changing the progression or severity of the disease after the onset of spontaneous seizures) may be related, but distinct, phenomena. Each will likely require different approaches to study the underlying mechanisms and to identify effective interventions. In addition, the epilepsies are characterized by many different etiologies, co-occurring conditions and phenotypic features; it is possible that specific etiologies will require targeted treatment(s).

Several potential anti-epileptogenic targets have been identified in various types of epilepsy and appear to show great promise for therapeutic development of compounds, biologics, or devices to modulate target activity. However, there are no projects in full-scale translational development in NIH programs like the NINDS Blueprint Neurotherapeutics Program (BPN), the Cooperative Research to Enable and Advance Translational Enterprises for Biotechnology Products and Biologics (CREATE Bio) program, or the CREATE Devices program.

Barriers to translation appear to include issues such as; limited data supporting reproducibility, robustness and timing of effect in animal models, poor alignment between preclinical experimental conditions and the clinical scenario in which an intervention could feasibly be delivered, and insufficient characterization of the assays, tools, and models needed to support a full-scale translational effort. Likewise, barriers to future clinical trials of disease modifying or prevention therapies include; limited ability to predict which subjects are at high risk for developing epilepsy, insufficient methods to predict disease severity or progression at the time of epilepsy diagnosis, lack of candidate markers of epilepsy to test as surrogate endpoints, limited experience with appropriate trial designs to efficiently evaluate disease modifying or prevention therapies, and the more general difficulty in recruiting and retaining subjects in clinical trials. A high-risk, multidisciplinary, collaborative CWOW initiative that fills some of these preclinical and clinical gaps for one or more particular targets may help enable progress toward approval of a first-in-class therapy for epilepsy prevention or disease modification.

Scope

Specific Objectives of the Research Program

The intent of this CWOW FOA is to support multidisciplinary studies whose results will build a rigorous and compelling scientific rationale for NIH and/or industry partners to fund future full-scale translational and clinical development of therapies for epilepsy prevention or disease modification.

Applications for an Epilepsy CWOW should come from a multidisciplinary, collaborative team proposing highly synergistic research projects and appropriate cores. Applicants are encouraged to form the strongest teams to address the research questions, regardless of geography or prior history of collaboration.

Applications for this CWOW may focus on any clinical population with, or at risk for, epilepsy (including rare forms of epilepsy) as long as the knowledge gained from results of the CWOW has a reasonable potential to be applicable to a broader segment of the population with epilepsy, and/or to contribute to our understanding of underlying mechanisms that may be common to more than one form of epilepsy.

A CWOW application should include both preclinical studies and clinical studies (described below), appropriate to the state of the field for a given topic. An application can focus on development of a disease-modifying therapy or a prevention therapy, or more rarely, a therapy that may be useful for both kinds of outcomes in different clinical populations. (In such cases, applicants are strongly encouraged to be extremely specific about the intended therapeutic outcome and population when describing the goals of a Project.) Applications must specify at least one intended therapeutic target, but may include multiple targets if appropriate.

Since this FOA specifically seeks applications that address difficult, challenging scientific questions and/or have the potential to overcome critical barriers in the field, applications may include components or Projects that are exploratory, discovery-based and/or higher risk in nature. Applicants should design the CWOW as a whole to have a significant impact on the field during the terms of the award weighing the balance of more conventional approaches with highly innovative components or Projects in which success is not guaranteed. In proposing higher risk components or exploratory Projects with limited preliminary data, applicants should describe the potential to achieve transformative, paradigm-shifting advances along with risks and potential pitfalls. Applicants should propose studies that, despite being exploratory or high-risk, have a likelihood of producing interpretable results. For example, if proposing a novel hypothesis, investigators should be able to support or disprove that hypothesis by the end of the funding period; if proposing exceptionally innovative methodology or technology, investigators should be able to develop it by the end of the funding period or demonstrate conclusively that the approach is not feasible.

Preclinical studies: A CWOW application must include one or more preclinical studies designed to test the rationale for moving one or more proposed compound, biologic, device or approach into therapeutic development. Preclinical studies should be rigorously designed (see NOT-OD-15-103), and use clinically relevant models of disease at appropriate developmental ages that recapitulate, to the extent possible, the etiology, underlying disease mechanisms, and symptoms of the human epilepsy being studied. In most cases, applicants should plan to include sex as a biological variable, as outlined in NOT-OD-15-102. A CWOW application may include, but is not limited to, studies that seek to establish rigorous preclinical proof of efficacy and evidence of target engagement, develop in vitro assays, explore preliminary pharmacokinetics, pharmacodynamics and toxicity, assess tolerance after repeated exposures, or evaluate appropriate treatment windows, duration, or dosing and route of administration paradigms. (Note, there will be some overlap between the scope of what can be proposed in applications for this RFA and the scope of activities proposed in applications for the new NINDS IGNITE program.)

Clinical studies: A CWOW application must include one or more clinical studies that will help facilitate the rigorous design and conduct of future trials. Such clinical projects may include, but are not limited to, studies in clinical populations or healthy volunteers to 1) identify robust biomarkers of risk, disease progression, or target engagement, 2) stratify participants, 3) pilot new clinical outcome measures (if existing measures are inadequate), or 4) explore new study designs that could be used to efficiently evaluate disease-modifying or prevention treatments in future trials.

Activities that are not responsive:

1) Applicants should note that translational activities that are supported in the NINDS 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 unless the application includes an Investigational Device Exemption from the FDA, or the device has already been cleared through the 510(k) or has premarket approval (PMA) pathways for the intended use. Please see www.ninds.nih.gov/otr full descriptions of the appropriate translational development 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 are not responsive this FOA. The NIH definition of "clinical trial" was recently revised, and is now "A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." Please see Guide Notice NOT-OD-15-015 for additional details. Applicants who wish to propose clinical trials should review www.ninds.nih.gov/research/clinical_research/index.htm for NINDS clinical trials FOAs.

3) Applications that fail to include BOTH preclinical and clinical study project aspects, or that fail to specify at least one intended therapeutic target, are not responsive to this FOA. Applicants seeking support for projects that are stand-alone, single-component basic, translational, clinical studies or trials in epilepsy should contact the Scientific/Research Contact listed in Section VII. Agency Contacts below for guidance on funding opportunities for these specific types of projects.

Required components:

Each CWOW application must have at least three research Projects, an Administrative Core, and a Public Engagement Core. Scientific Cores may be included if needed. The proposed number and composition of 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.

Projects: The CWOW application must include three or more related, integrated, synergistic and high-quality research Projects that provide a multi-disciplinary, yet thematically unified, approach to the problem to be investigated.

Administrative Core: An Administrative Core is required and the Program Director(s)/Principal Investigators (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. The Administrative Core will also be responsible for maintaining 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.

Public Engagement Core: Each CWOW must have a core that promotes two-way communication between the CWOW investigators and the community of individuals with epilepsy and caregivers. The purpose of this partnership is to lay the groundwork for successful recruitment and retention in future clinical trials of the proposed intervention. This partnership should inform investigators about patient concerns and feasibility of future trials of the planned intervention in this population (such as risk/benefit determination, burden of visits and procedures, etc), and inform the patient community about current therapeutic research avenues and plans for future definitive trials of efficacy and safety.

Scientific Core(s): Scientific Cores may be proposed as necessary, but must be justified in terms of the scientific Projects. A Scientific Core must provide support to two or more Projects.

Ideally, at their completion, the CWOW activities will have generated 1) a rigorous evidence base (i.e., the "scientific premise") that justifies further therapeutic development of one or more therapies for preventing or modifying epilepsy, 2) a data package that meets the entry criteria for subsequent application to the NINDS translational programs or to engage a private industry partner 3) sufficient information about the clinical population to design appropriate and feasible trials, and 4) an engaged group of research partners composed of people representing those with the target disease, whose involvement will help in the appropriate design and efficient recruitment and retention of subjects in future definitive trials of the intervention(s).

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."

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

Milestones

Because therapeutic development is an inherently high-risk process, applications must propose one or more milestones associated with each Specific Aim. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the Project, 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 yearly evaluations of progress of the CWOW as a whole.

Prior to funding an application, NINDS program staff 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 NINDS program staff.  NINDS program staff may consult as necessary with independent consultants with relevant expertise. 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.

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 12 weeks before the receipt date. 

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.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

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 - Including the NIH Intramural Program
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• 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.
  • 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.

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.

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

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

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

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

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.

It is critical that applicants follow the 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, it is strongly recommended and 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:

Brandy Fureman, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917
Email: furemanb@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	12
Core (use for Public Engagement Core)	12
Core (use for Scientific Core (Optional))	12
Project	12

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

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
• Public Engagement Core: required
• Scientific Core: optional
• Projects: at least 3 required

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.

Complete entire form.

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

Follow standard instructions.

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.

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.

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.

Specific Aims: The specific aims should briefly but specifically describe the goals of the proposed CWOW and summarize the expected outcome(s). An overall CWOW milestone should be included for each Overall specific aim.

Research Strategy: The Overall Research Strategy should describe the major theme of the CWOW, its goals and objectives, background information and the overall importance of the research to the development of therapies to modify or prevent epilepsy.

All CWOW applications should include:

1) A brief description of the intended clinical population, including incidence, prevalence, natural history, diagnostic process and current standard of care. If studying a rare disease, an explanation of how the mechanistic knowledge gained from the CWOW studies will be valuable to a broader range of the population with or at risk for epilepsy.

2) A justification of the rationale for intervening in the specific epileptogenic mechanism(s) chosen, using one or more candidate therapies (compound, biologic, and/or device)

3) A statement about the expected therapeutic outcome if the therapy is ultimately shown to be effective (i.e., is the therapy expected to prevent seizures? Is the therapy expected to reduce seizure frequency or severity? Is the therapy expected to produce improvements in cognition or developmental outcomes?)

4) The key questions that, if answered in the CWOW, would help to build a compelling scientific premise for full-scale development of the candidate therapeutic agent(s). The project and core activities included in the CWOW application should be designed to directly answer these key questions about the population, the therapeutic agent (s), and/or the mechanism(s).

Describe the rationale for the total proposed program. Explain the strategy for achieving the goals defined for the overall program and how each research project and core relates to that strategy and to each other. A successful CWOW application will include a well-integrated research strategy that clearly shows how the proposed projects and cores are highly synergistic and will foster therapeutic development of one or more disease modifying or prevention therapies for a specific population with epilepsy. The program should be viewed as interrelated research Projects, each of which is not only individually scientifically meritorious but is complementary to the other Projects and related to the overall theme developed for the CWOW. Provide justification in the application that: (a) the proposed Projects are such that they require an intensive collaborative effort to succeed and (b) that key personnel will collaborate effectively.

Describe the organizational structure of the CWOW. Also describe any connections between the proposed CWOW and any other organizations such as non-profit voluntary groups or industry partners.

As the research strategy is prepared, it is important to note that NINDS believes that applications that propose preclinical research, or clinical applications that are based on previous preclinical data, 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 shows consideration for the epilepsy-specific issues described in Simonato et al., 2014 and other biological variables described in NOT-OD-15-102.

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. Letters of support should indicate the specific activities the individual or organization will perform in pursuit of the CWOW goals; letters of support from individuals or organizations without a specific role in the CWOW should not be included.

Collaboration with NIH Intramural Researchers: NIH Intramural Researchers may participate in the CWOW as investigators or collaborators, with their roles and activities detailed in the corresponding Project or Core component of the CWOW application. However, CWOW funds may NOT be used to support the activities of 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.
• CWOW awards are required to include NINDS Common Data Elements (CDEs) where applicable.
• Applicants should confirm that the consent forms for funded projects specifically address the following: (1) disclosure that biological materials and clinical data may be distributed to other researchers in both academia and in industry; (2) assurance that such data will be stored and maintained without personal identifiers; (3) disclosure that analyses of these data may be conducted by other scientists currently not included within the current research team, potentially including those with commercial interests; (4) that the data collected by the researchers may be used as necessary to study any other disorder.

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.

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.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Other attachments: The CWOW application must include a Charter with detailed policies regarding publication and assignment of intellectual property rights, as well as plans for sharing pre-competitive data, reagents and methods with the broader epilepsy research community as appropriate.

The Charter should also include:

• An Organizational Chart
• Guidelines for authorship on all publications resulting from research supported by the CWOW award.
• Guidelines for assignment of intellectual property rights among CWOW collaborators
• Plans for sharing pre-competitive data, reagents and methods with the broader epilepsy research community as appropriate.
• Discussion of the use of the NINDS Common Data Elements for all proposed clinical studies (http://www.nindscommondataelements.org/default.aspx ).
• Discussion for the utilization, as appropriate, of current NINDS-funded resources such as the NINDS Biospecimen Repository at Coriell, other Epilepsy Center Without Wall initiatives, the International Epilepsy Electrophysiology Portal (IEEG), dbGaP, etc.
• Schedule for reports to NINDS and relevant oversight committees on all issues related to individual Project and Core performance.
• Milestone goals and deliverables that set performance expectations for continued funding of individual Projects and Cores
• Additional policy and procedures for the CWOW as appropriate.

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.

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.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core 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 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.

Specific Aims: The specific aims should briefly but specifically describe the goals of the proposed Administrative Core and summarize the expected outcome(s). An Administrative Core milestone should be included for each specific aim.

Research Strategy: The Administrative Core will be responsible for the management and administration of the overall CWOW. This section of the application should describe the strategies and processes that will be used to manage the CWOW and achieve the goals. This Core will provide oversight for the projects and cores, promote coordination and collaboration within the CWOW and with investigators and organizations outside the CWOW. The Administrative Core will also be responsible for developing and maintaining a website to publicly communicate the mission and goals of the CWOW, to advertise the availability of shared resources and activities of the Public Engagement Core to the rest of the community, and to provide a protected internal platform for CWOW investigators to communicate and share data as appropriate. A description of plans for overall project management through the lifetime of the CWOW should be provided in the application, to include the planning and coordination of research activities; the integration of cross-disciplinary research; development of project and core milestones and deliverables, oversight of fiscal and resource management; and the maintenance of ongoing communication. Indicate who will be responsible for each of these activities. Applicants should specify appropriate administrative/business management staff and oversight mechanisms by the CWOW Director(s) and Executive Committee.

Provide a communication plan for 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. When multiple performance sites are planned, the Administrative Core should include leadership and communication plans adequate to manage the multiple sites.

The Administrative Core should establish an Executive Committee, composed of key members of the CWOW and NINDS staff.

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:

• The Administrative Core should provide oversight of the resource sharing plans of the CWOW. A competitive application is expected to provide a plan regarding the timely sharing of specimens, cells, animal models and redacted data generated with support from this award with other qualified research scientists, both within and outside the CWOW, and ensuring that such data are HIPPA 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 Anticonvulsant Screening Program.

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.

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

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

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

The Public Engagement Core is a required component to provide concrete opportunities for two-way communication between the CWOW investigators and people with epilepsy, caregivers, and epilepsy-related non-profit voluntary organizations towards the goal of partnering in clinical research and future trials of disease modifying or prevention therapy.

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

SF424 (R&R) Cover (Public Engagement 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 (Public Engagement Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Public Engagement 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 /Performance Site Location(s) (Public Engagement 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 (Public Engagement Core)

• Applicants are strongly encouraged to involve a representative of an epilepsy-related non-profit voluntary organization in the leadership of the Public Engagement Core.
• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core 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 (Public Engagement Core)

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

A CWOW application may include funds to support allowable activities of a representative of an epilepsy-related non-profit voluntary organization per the NIH Grants Policy Statement, but must NOT be used to support grassroots lobbying or direct lobbying by grantees (For additional detail, please see NIH guidance at http://grants.nih.gov/grants/lobbying_guidance.htm). If any part of the representative's activities in the Public Engagement Core will be funded through the CWOW budget, please provide sufficient detail in the Public Engagement Core Approach to determine whether these activities are "allowable" or "not allowable" according to the Guidance provided at http://grants.nih.gov/grants/lobbying_guidance.htm

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 (Public Engagement Core)

Specific Aims: The specific aims should briefly but specifically describe the goals of the proposed Public Engagement Core and summarize the expected outcome(s), including the impact on the ability to design or conduct future trials of disease modification or prevention and on the patient community as a whole. A Public Engagement Core milestone should be included for each specific aim.

Research Strategy: The Public Engagement Core will be responsible for coordinating activities among CWOW investigators, people with epilepsy, caregivers, and epilepsy-related voluntary organizations. The purpose of this partnership is to lay the groundwork for successful recruitment and retention in future clinical trials of the proposed intervention. This partnership should inform investigators about patient concerns and feasibility of future trials of the planned intervention in this population (such as risk/benefit determination, burden of visits and procedures, etc), and inform the patient community about current therapeutic research avenues and plans for future definitive trials of efficacy and safety. This section of the application should describe the strategies and processes that will be used to engage the appropriate population of people with epilepsy, caregivers, and epilepsy-related non-profit voluntary organizations in ways that will encourage their partnership with investigators in current or future clinical research studies and trials. An example includes, but is not limited to, an application that proposes a Public Engagement Core focused on consultation with the intended patient population to provide feedback on eligibility criteria, study procedures, safety and confidentiality issues, acceptable risk/benefit ratios, meaningful outcome measures, and successful enrollment and retention strategies for a future trial of disease modifying or prevention therapy. Another example is a Public Engagement Core that conducts outreach activities to increase the number of individuals from the intended patient community who are knowledgeable about and willing to participate in the design, review, conduct, or oversight of clinical research studies and trials. Developing a de novo contact registry for research participation is discouraged unless there is strong justification of unique need, as there are several publicly available tools for this purpose (e.g. the Rare Epilepsy Network, ResearchMatch.org, Human Epilepsy Research Opportunities (EpilepsyHero.org)).

A narrative description should be provided that includes the planning and coordination of these activities, as well as methods for evaluating their impact.

Letters of Support: Include letters of support for the collaborative/cooperative arrangements, subcontracts, or consultants, including the specific roles the representative(s) of an epilepsy-related non-profit voluntary organization will play in the CWOW activities. The letter should also indicate whether funding is available from the partnering organization to support the representative's activities in whole or in part.

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:

Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected.

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.

Planned Enrollment Report (Public Engagement Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Public Engagement Core)

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

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.

A Scientific Core is not a required component, but may be included if justified by the needs of the CWOW Projects. A Scientific Core must support at least two Projects.

SF424 (R&R) Cover (Scientific 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 (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific 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 /Performance Site Location(s) (Scientific 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 (Scientific Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core 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 (Scientific 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 (Scientific Core)

Specific Aims: The specific aims should briefly but specifically describe the goals of the proposed Scientific Core and summarize the expected outcome(s). A Scientific Core milestone should be included for each specific aim.

Research Strategy: A Scientific Core must support at least two Projects. Describe the function of the Scientific Core as a resource to the CWOW. This section must clearly present the facilities, techniques, and professional skills that the Core will provide. A core is principally designed as a service or resource component; it would be highly unusual to include research in a core (a possible exception would be methodology development). Applicants should contact the Institute staff if further guidance is needed.

Describe the role of the core as a resource to the CWOW as a whole. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each Project in the program. To aid in the review of the application, please include a table of information concerning the scientific Projects that the core would serve and the proportion of the cost of the core associated with each research Project involved.

Cores may already exist in some form prior to the application. When proposing support for an already existing Core, describe how the CWOW award would enhance the resources or services already available through new innovation and technology development, expanded availability, increased throughput, etc.

Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants, including the specific role the individual(s) will play in the CWOW activities.

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:

Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected.

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.

Planned Enrollment Report (Scientific Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Scientific Core)

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

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 (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 (Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (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) (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 (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 (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 (Project)

Specific Aims: The specific aims should briefly but specifically describe the goals of the proposed Scientific Project and summarize the expected outcome(s), including the impact the proposed research will exert on the field and the key questions that will be addressed by the Project results. A Project milestone should be included for each specific aim.

Research Strategy: Clearly state the overall objective and explain the relevance of the Project to the central theme of the CWOW. In addition, an explanation should be included describing how the Project addresses a key question that will enable future translational or clinical development of a disease modifying or prevention therapy. Applicants are strongly encouraged to be extremely specific about the intended therapeutic outcome and population when describing the goals of a Project. Without reiterating the overall synergy described in the Overall component, describe how the Project is synergistic with other research Projects and Cores of the CWOW. Applicants should address why the Project is best suited to be carried out in the CWOW environment, and not in a standard NIH funding mechanism (e.g., R01).

A CWOW application should include Projects focused on preclinical studies and clinical studies, which are appropriate to the state of the field for a particular population and indication.

Preclinical studies: A CWOW application must include one or more preclinical studies designed to test the rationale (the scientific premise) for moving one or more proposed compound, biologic, device or approach into therapeutic development. Preclinical studies should be rigorously designed (see NOT-OD-15-103), and use clinically relevant models of disease at appropriate developmental ages that recapitulate, to the extent possible, the etiology, underlying disease mechanisms, and symptoms of the human epilepsy being studied. A CWOW application may include, but is not limited to, studies that seek to establish rigorous preclinical proof of efficacy and evidence of target engagement, develop in vitro assays, explore preliminary pharmacokinetics, pharmacodynamics and toxicity, assess tolerance after repeated exposures, or evaluate appropriate treatment windows, duration, or dosing and route of administration paradigms.

Clinical studies: A CWOW application must include one or more clinical studies that will help facilitate the rigorous design and conduct of future trials. Such clinical projects may include, but are not limited to, studies in healthy volunteers or clinical populations to 1) identify robust biomarkers of risk, disease progression, or target engagement, 2) stratify participants, 3) develop new clinical outcome measures (if existing measures are inadequate), and 4) explore new study designs that could be used to efficiently evaluate disease-modifying or prevention treatments in future trials. NIH-defined clinical trials are not permitted in this FOA.

Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants (only include letters that reflect formal collaborations, not general letters of recommendation).

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:

Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected.

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.

Planned Enrollment Report (Project)

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

PHS 398 Cumulative Inclusion Enrollment Report (Project)

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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.

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.

This initiative is not subject to intergovernmental review.

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.

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.

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 NINDS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.   As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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.

For this particular announcement, note the following:

A CWOW application must include the following components: At least three Research Projects, an Administrative Core, and a Public Engagement Core. Scientific Cores may be included if needed. The proposed number and composition of 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, but must include both preclinical and clinical studies. Each individual component will be evaluated, discussed, and assigned an individual component score that represents enthusiasm for each component. After the review of the individual components, an overall impact score will be assigned to the application. The overall score for the CWOW application may be higher or lower than the average of the individual components based on the assessment of whether the whole is greater than the sum of its parts. At least three integrated, synergistic and high-quality scientific Projects must be included.

Since this FOA specifically seeks applications that address difficult, challenging scientific questions and/or have the potential to overcome critical barriers in the field, the NINDS recognizes that applications may include components or Projects that are exploratory, discovery-based and/or higher risk in nature. The review will evaluate the potential for the CWOW as a whole to have a significant impact on the field during the terms of the award weighing the balance of more conventional approaches with highly innovative components or Projects in which success is not guaranteed. In evaluating higher risk components or exploratory Projects with limited preliminary data, the reviewers will weigh the potential to achieve transformative, paradigm-shifting advances against the risks. The reviewers will evaluate the likelihood that interpretable results will be obtained from exploratory or high risk studies. For example, if proposing a novel hypothesis, the investigator should be able to prove or disprove that hypothesis by the end of the funding period; if proposing exceptionally innovative methodology or technology, the investigator should be able to develop it by the end of the funding period or demonstrate conclusively that the approach is not feasible.

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).

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.

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

Does the CWOW application focus on a clinical population and interventional strategy that will result in significant breakthroughs for affected individuals? If the CWOW is focused on a rare disease population, does the knowledge gained from results of the CWOW have a reasonable potential to be applicable to a broader segment of the population with epilepsy so that successes may be extended to other types of epilepsy? Are the expected results likely to provide a compelling scientific rationale for additional translational research investment? Will successful completion of the aims result in one or more therapeutic leads for disease modification or prevention that can be advanced through translational development? Will the clinical studies proposed in the application adequately prepare the investigators and the community for future disease modifying or prevention trials? Will the proposed public engagement activities adequately prepare the investigators and the community for future disease modifying or prevention trials?

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?

Are the qualifications, experience, and commitment of the Director(s) of the CWOW adequate to lead the CWOW? Are they devoting sufficient time/effort to achieve the goals? Does the CWOW Director(s) have sufficient authority and credibility within the institution and broader research community as a base for serving a national leadership role in epilepsy related research? If more than one CWOW Director is proposed, are clear leadership plans in place?

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

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

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?

In evaluating higher risk components or exploratory Projects with limited preliminary data, does the potential to achieve transformative, paradigm-shifting advances outweigh the risks? Is it likely that results from exploratory or high risk studies will be interpretable?

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?

Scored Review Criteria - Projects

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

Significance

Does the Project address an important problem or a critical barrier to progress in the field? If the aims of the Project are successfully completed, will a key question needed for future therapeutic development have been answered? How will successful completion of the aims change the treatments, services, or preventative interventions that drive this field?

Does the Project integrate well into the overall theme of the CWOW? Does the Project appear to present opportunities for synergy and iterative progress with the other Projects included in the CWOW?

Investigator(s)

Are the qualifications, experience, and commitment of the investigator (s) adequate to lead the Project and are they devoting sufficient time/effort to achieve the goals? Are the investigator(s), collaborators, and other researchers well suited to the Project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the Project is collaborative, 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? 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? If limited preliminary data is available, does the potential to achieve transformative, paradigm-shifting advances outweigh the risks? Is it likely that interpretable results will be obtained from exploratory or high risk studies?

Is the proposed Project rationale based upon a sufficiently rigorous body of high quality preclinical or clinical research? Is there evidence of rigor in terms of rationale, preliminary data, experimental design and strategies to minimize bias?

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? Are there appropriate plans for the rigorous management and quality control of any research data or materials to be obtained from human subjects? If included, is the patient cohort well-defined and appropriately diverse? Are plans in place for patient recruitment? Will clinical data be collected using the NINDS Common Data Elements (CDEs)? Is the timeline for Project activities included and adequate?

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?

Scored Review Criteria - Cores

In contrast to the review of Projects, reviewers will not provide individual criterion scores for Cores and will assign an overall numeric rating only. The review criteria for the individual Cores are provided below.

Administrative Core

Does the leader(s) of the Administrative Core have appropriate expertise and dedicate sufficient time to administrative activities? Is the line of communication clear between the CWOW Director and the Administrative Core Leader? Is the proposed management structure appropriate for scientific administration as well as fiscal administration, procurement, property and personnel management, planning and budgeting? Is there an appropriate plan for establishing and maintaining effective communications and cooperation among CWOW investigators and with investigators outside the CWOW? Are plans for development of the public CWOW website adequate? Are there internal and external procedures for monitoring and evaluating the proposed research Projects and Core facilities/resources? Are there appropriate plans for management of data, animal models and other resources? Does the Administrative Core component contain the required Attachment containing the CWOW Charter, and does the Charter include the elements requested in this FOA?

Scientific Cores

Is the Scientific Core essential to advance the scientific aims of at least two proposed research Projects? Is the Core connected to the central theme of the overall program? How valuable are the facilities or services provided by the Core (including procedures, techniques, and quality control)? Are they being used effectively? Are the Core Lead and key personnel well-qualified to provide the Core service(s)?

If human subjects, vertebrate animals, or biohazards are to be used in a Core, the adequacy of these sections will be assessed and will be considered in evaluating the individual Core. Are there appropriate plans for the rigorous management and quality control of any research data or materials to be obtained from human subjects? If included, is the patient cohort well-defined and appropriately diverse? Are plans in place for patient recruitment? Will clinical data be collected using the NINDS Common Data Elements (CDEs)? Is the timeline for Core activities included and adequate?

Public Engagement Core

Does the Public Engagement Core Lead have appropriate expertise and dedicate sufficient time to engagement of Core activities? Is the line of communication clear between the CWOW Director and Public Engagement Core Lead? Are there appropriate plans for outreach activities that will contribute to the education and/or direct involvement of people with epilepsy, caregivers and/or epilepsy-related non-profit voluntary organizations in the research conducted by the investigators in the CWOW? Will the activities of this Core provide a foundation for future clinical trials of safety and efficacy of a disease modifying or prevention therapy?

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.

Is there synergy between the components that could not be achieved through standard NIH award mechanisms? Are there clear advantages of conducting the proposed research as a program rather than through separate research efforts? Will the research proposed in individual Projects directly inform the conduct or interpretation of other CWOW Projects? Is the CWOW as a whole focused on a cohesive theme?

Milestones:

Are milestones in Projects robust and associated with clear, quantitative criteria for success that allow go/no-go decisions? Will the Overall CWOW milestones provide adequate information to evaluate yearly 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? 

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.

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.

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

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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

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 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.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

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

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.

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the 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.

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

The overall function of the CWOW as described under "Specific Research Objectives". This includes the development of the standard operating procedures, and consistent emphasis on collaborative interactions between all CWOW investigators, advisory and steering committees, and NIH representatives. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

An NIH 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 NIH policies and procedures, and is consistent with the mission of the NIH to improve public health; and (3) serving as a point of contact for investigators with the NIH; (4) disseminating information from the Institute and communicating with Institute leadership to ensure that the CWOW operates smoothly.

An NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The NINDS Project Scientist and staff will work closely with the Steering Committees, and the PD(s)/PI(s) of all Projects and Cores in order to ensure proper conduct of the CWOW.

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.

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
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
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Brandy Fureman, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917
Email: furemanb@mail.nih.gov

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

Tijuanna DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

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

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