Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

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

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

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose:

This funding opportunity announcement invites applications for participation as the Clinical Coordinating Center (CCC) in the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT). The purpose of the network is to efficiently conduct multiple, scientifically sound, possibly biomarker-informed exploratory clinical trials evaluating the most promising therapies, and to facilitate collaborations between academia, industry, non-profit foundations, government organizations, and other possible stakeholders. The main focus of the network is the conduct of phase 2 clinical trials. Studies of biomarker validation are also eligible, if a multicenter network setting is necessary. In addition, the network will serve as the vehicle for the conduct of early clinical trials of gene therapy for ultra-rare neurological disorders. Where the nature of the study population warrants it, phase 2-3 trials are acceptable. The CCC will also coordinate the conduct of gene-based or transcript-directed therapeutics, such as oligonucleotides and viral-based gene therapies, for ultra-rare neurological or neuromuscular disorders, through the Gene Therapy Consortium.

The network provides a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. While the network is not specific to one disease, it has the capacity to coordinate a cadre of specialist investigators to implement studies efficiently in response to disease-specific opportunities. The network will set up master protocols if warranted for specific patient populations or therapeutic assets.

Background:

NeuroNEXT was established in 2011, in order to provide an efficient structure for the conduct of high-quality, collaborative clinical trial studies, focusing on the phase 2 clinical trial space, as a particularly challenging and impactful area of clinical research. 11 studies have been or are being conducted in the network since inception. A recent network review has highlighted opportunities for improvement and progress, which are reflected in this FOA.

Research objectives:

The network aims to share expertise and infrastructure across diseases, to leverage research resources at clinical sites, and to flexibly take advantage of clinical research opportunities as they arise in different disease areas. Finite resources and especially for rare diseases a small pool of potential participants limit the number of large, confirmatory efficacy (Phase 3) trials that can be conducted at any given time. Therefore, NINDS aims through the network to support trials that can provide more rapid preliminary testing of new treatments.

The network will streamline the implementation of clinical research by using standardized master trial agreements and infrastructure that utilizes a central IRB of record, and is designed to assure the broadest access to any new therapies for patients by carrying out trials coming from partnerships between NINDS and industry, foundations, or academia.

Shared network infrastructure:

This FOA solicits applications for funding of infrastructure for trial coordination. The additional project-specific funds to support the implementation of network protocols will be part of separate, trial-specific awards. These funds will be distributed to the Clinical Sites via the CCC on a per-patient basis, according to protocol budgets approved by the network Steering Committee (SC) and via master trial agreements with the Clinical Sites.

The network will utilize a central IRB of record, which operates consistent with the NINDS Central IRB policy. The CCC coordinates the central IRB of record and manages all required IRB communication and documentation including but not limited to tracking approval, maintaining regulatory documents, communicating with the local IRBs, and handling adverse event reporting and notifications.

Network trials:

Project proposals from industry and academic investigators are submitted in response to separate announcementss, and are selected for funding through the standard NINDS process as outlined in the related announcements.

The network trials utilize a variety of the NIH agreement mechanisms (e.g., Cooperative Research and Development Agreements [CRADAs]) that maximize industry participation and support.

Following a second level of review by the NINDS advisory council, NINDS will select protocols to be fully developed by a protocol lead team consisting of the Project Director/Principal Investigator (PD/PI), disease-experts as co-investigators, and network representatives. Patient representatives and patient advocacy groups must be included in the protocol development process and in review of manuals of operation as well as organizational and oversight committees.

The final protocol will be approved after technical review by a Protocol Review Committee. A subset or all of the Clinical Sites will then be invited to participate in a given project and will have the option to accept or decline, depending on their capacity, interest, and patient population relevant to the specific protocol. It is also possible that non-network sites may be added ad-hoc for a specific project, for their expertise and patient population to complement network sites.

Research topics:

The Clinical Coordinating Center's Scope of Work includes, but is not limited to:

• Overseeing from conception to analysis/publication the implementation of complex, multi-center clinical projects
• Monitoring human subjects' protection and adequate gender and minority representation among subjects enrolled at network Clinical Sites
• Coordinating all network Steering Committee (SC) activities including, but not limited to organizing teleconferences at least twice monthly, and in-person meetings as needed, maintaining documentation such as meeting minutes of SC activities, and coordinating the network SC working groups. SC working groups are established on an as-needed basis to develop and oversee the implementation of specific protocols, and to provide in-depth evaluation and recommendations on such issues as publications/presentations, quality control, conflict of interest, per-patient budgets, pipeline and applications, pediatric study matters, telemedicine use and implementation, and others
• Coordinating and documenting all communication, and reporting between the CCC, clinical sites, central IRB of record, and local IRBs, which includes but is not limited to maintaining documentation of IRB initial approvals, amendment approvals, and adverse event and other reports.
• Establishing standardized master trial agreements with the network Clinical Sites and developing and implementing a plan to reduce the start-up time of each network project through the use of these standardized master trial agreements and the distribution of network approved per-patient cost according to these agreements
• Coordinating study drug management, including but not limited to drug and placebo acquisition, delivery plan for bulk drug, secondary packaging/labeling/distribution/storage, blindedness testing, coordinating stability testing and accommodating expiration timelines, and drug accountability, and management of the central pharmacy.
• Working with the Project SC and IND sponsor (investigator or industry partner) on obtaining FDA regulatory approval for the trial (IND/IDE or exemption), and on reporting, documenting and coordinating follow-up correspondence
• Working closely with the DCC in a collaborative and interactive manner. The CCC and DCC, once selected for potential funding, will submit to the NINDS jointly their respective Standard Operating Procedures (SOPs), revised from the version originally submitted as part of the application, based on their jointly developed collaboration plan. They will also submit a scope of work document that details the division of tasks and responsibilities within the budget they had proposed. It is essential that the tasks required in planning and executing a complex, multi-centered trial be clearly defined, and that the responsibilities of the collaborators (including CCC and DCC) be delineated. It is therefore required that the joint DCC and CCC SOPs and scope of work document show excellent and seamless communication and coordination and reflect an in-depth understanding of the overall operational conduct of a complex, multi-center trial
• Providing collaborative leadership to the Clinical Sites, including to potential ad-hoc sites

During the conceptual phase of approved projects:

• Working with potential new project investigators in determining appropriateness of their project for network infrastructure access
• Providing information necessary to the potential investigators as they apply for NINDS funding (e.g., review protocol synopsis and schedule of activities, create project workscope and timeline, ensure the feasibility of the proposed projects by analyzing the numbers of potentially eligible participants at the proposed sites and by including patient representatives in the conceptual process)
• Supporting the investigators in the IND/IDE submission if needed

During the planning phase of approved projects:

• Working with project lead team of investigators to finalize the protocol and consent form
• In collaboration with the DCC, working on case report forms (CRFs)
• Participating in site selection
• Developing a written, detailed patient recruitment plan, with attention to adequate recruitment of populations previously under-represented in research.
• Monitoring the IRB approval process and promoting rapid approval through well-developed and complete documentation at the initial submission, and through rapid and comprehensive responses to any IRB comments or concern
• Collecting regulatory documents (1572 forms, biosketches, Good Clinical Practice [GCP] certifications, etc.)
• Finalizing details of per-patient payments to sites within approved budget, developing site payment schedule, finalizing subcontracts with sites per master trial agreements
• Finalizing study drug packaging and labeling
• Holding investigator meetings and ensuring initial study personnel training for GCP and protocol adherence
• Working with the DCC as they establish a trial database

During the implementation phase of approved projects:

• Overseeing the enrollment of eligible subjects
• Tracking enrollment and retention and developing outreach interventions as needed
• Working with sites to ensure adequate diversity in equitable participation of social and ethnic groups
• Distributing study drug to sites
• Working with sites to ensure appropriate protocol implementation and adherence to protocol and GCP
• Answering queries from the sites regarding protocol, drug dose adjustments, adverse events, premature withdrawals, etc.
• Conducting site visits, as needed
• Supporting the DCC in their monitoring and data quality assurance procedures

During the Analysis and Publication Phase:

• Assisting the DCC and sites in resolving final queries, finalizing reporting to the FDA and IRBs
• Coordinating the communication of the trial results to the investigators, patients and public
• Working with the DCC and network investigators in the publication of the primary and, if applicable, secondary manuscripts

New for this funding cycle, the CCC will also be responsible for organizing and maintaining a Gene Therapy Consortium (GTC). Gene therapy trials, either based on projects completing studies through the URGeNT program or proceeding directly to clinical trial phase, will also be selected for funding through the process outlined in the related announcements. The Ultra-Rare Gene-Based Therapy (URGenT) network supports Investigational New Drug (IND)-enabling studies and planning activities for First-in-Human (FIH) clinical testing of gene-based or transcript-directed therapeutics, such as oligonucleotides and viral-based gene therapies, for ultra-rare neurological or neuromuscular disorders. The goal is to accelerate the development of a promising clinical candidate with robust biological rationale and demonstrated proof of concept (POC) data for the intended approach in a model system relevant to a specified patient population towards an IND filing and the initiation of a clinical trial. The NeuroNEXT GTC will conduct clinical trials as the next step in development. Access to the GTC will not be limited to assets developed through the URGeNT network and applicants could enter the development pipeline directly at the clinical trial stage.

The GTC will consist of 6-10 members with expertise in gene-based and gene-targeted therapies, ultra-rare and rare diseases, and clinical trial planning and execution, with particular emphasis on first-in-human or first-in-disease trials, small clinical trials, and adaptive trial design.

Also new for this funding cycle, the CCC and DCC will organize, with the collaboration of network sites, network-linked open conferences to facilitate stakeholder discussions to identify areas of high unmet need and priority. At least one conference annually, in person if possible and virtual if necessary, will be organized focused on different disease or subspecialty areas for each iteration. The goal will be to proactively identify areas in which projects could be proposed to NINDS for implementation in the network. Participation will include at the minimum the members of the NEC and the members of the specific subspecialty interest group, representatives for the interest area from each site, unless already covered through NEC or interest group membership, key opinion leaders from outside the network, and other stakeholders as relevant to the subject area.

NeuroNEXT network structure and management:

The overall structure of the network includes the CCC, a Data Coordinating Center (DCC), and 25 geographically distributed sites. The CCC will oversee the GTC, which will be activated as needed for gene therapy trials of variable scale. The CCC works with successful applicants to efficiently implement funded studies.

• NINDS will be responsible for organizing and providing overall support for the network. The NINDS Division of Clinical Research staff and the NINDS Grants Management Branch will be responsible for the overall management of the network. In addition to regular grant stewardship, an NINDS Project Scientist will be involved substantially with the recipients as NINDS partner, consistent with the Cooperative Agreement mechanism. The NINDS has established an External Oversight Board (EOB) for NeuroNEXT. The EOB is an external group of experts whose mission is as follows:
• The External Oversight Board (EOB), consisting of experts in clinical trials, clinical neuroscience, therapeutics development, as well as patient advocacy, was selected by the NINDS to provide external perspectives on the network, including: review of network performance, evaluation of the NeuroNEXT study portfolio, assessment of the overall success of the initiative in meeting the initial goals, and setting priorities for network focus including corrective measures or changes in direction. The CCC will be responsible for the EOB, which is expected to meet annually.
• A Steering Committee (SC) composed of three principal investigators representing the Clinical Sites, the DCC PI, the CCC PI, plus the PIs of active network projects and the NINDS Project Scientist will be the main governing body of the network. NINDS will appoint an SC Chair to preside over SC meetings and serve as the SC representative to the SAB.
• All major scientific decisions will be determined by majority vote of the SC;
• Each SC member will have one vote; the SC Chair will cast a vote in case of a tie;
• The protocol lead PIs of approved network protocols will become SC members for the duration of the project they are leading;
• The initial three Clinical Site representative PIs will be appointed by NINDS to the SC for a 2 to 3-year term;
• The second slate of SC investigator-members will consist of the highest overall enrolling investigator and two investigators elected by their peer investigators to a 2-year term. For continuity, one of the three initial SC investigator members will serve on the committee for 2 years, and two will serve on the committee for 3 years, so that not all tenures expire at the same time;
• It is anticipated that the SC will meet two times per month by telephone conference call and at least yearly by in-person meetings, unless prevented by uncontrolled circumstances.
• The SC will have primary responsibility for network governance, and will advise on prioritizing protocols. SC working groups will be established by the SC to perform specific functions, such as, for example:
  • Protocol review, publications and presentations;
  • Per-patient budget approval;
  • Quality control assurance;
  • Conflict of interest;
  • Pediatric studies
• The DCC will support protocol development and implementation with regards to statistical design, data management, data quality assurance, and analysis;
• The DCC will also initiate and coordinate activities to promote standardization of data elements using the NINDS common data elements (CDEs) when available, or help develop common data elements and standardized protocols. See companion FOA for more details describing the responsibilities of the network DCC.
• The CCC will provide overall clinical coordination as described above.
• The Clinical Sites will facilitate efficient project start-up; will collect high quality data in adherence to the protocol and in compliance with the rules and regulations governing clinical research.
• The Clinical Sites will also participate in network-wide training, communications, and network SC activities, including network-SC working groups, as needed.

Gene therapy studies in rare disorders:

The GTC will work in collaboration with the CCC, DCC, clinical trial PI, and relevant sites as described above for NeuroNEXT trials. It is expected that only a small number of sites, or in some cases a single site, will be involved in some of the trials, due to the nature of the patient population and intervention. The sites involved in the gene therapy trial may be NeuroNEXT sites or external sites depending on individual project needs.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Government

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

Other

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

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

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

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

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

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Only one CCC application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. However, applicants may apply for an award for the DCC or Clinical Site (separate FOAs) as well as for an award under this FOA.

Awards for a CCC and a DCC will not be made to the same Principal Investigator, to ensure that data analyses and data acquisition are performed independently.

Awards for a CCC and a Clinical Site may be made to the same institution.

However, it is preferred that the CCC and a Clinical Site at the same institution be led by separate investigators, to ensure that the CCC activities as well as the local Clinical Site activities receive full attention.

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Joan Ohayon
Telephone: 301-496-9135
Email: [email protected]

All page limitations 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 an application to this FOA.

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

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

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

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

The applicants should outline prior experience in managing multicenter trial infrastructures and the planning and execution of multicenter clinical trials in the personal statement and relevant publications portion of their bio-sketch.

R&R or Modular Budget

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

A detailed budget for the CCC should be presented. The budget must include all activities delineated in the list of CCC responsibilities included in this FOA.

All activities related to coordinating at least 5-7 clinical research studies, should be budgeted, including:

• Start-up activities;
• Regulatory approvals;
• Training and investigator meetings, SC and other leadership committee functions;
• Site visits;
• Communication, documentation and reporting required to operate a central IRB of record;
• Study drug management;
• Collecting regulatory documents;
• Working with potential network investigators in the protocol conception development and implementation phases.
• Maintaining the gene therapy consortium
• Network-linked open conferences to discuss areas of unmet need and priorities
• In addition, administrative tasks related to subcontracting with Clinical Sites, monitoring recruitment and protocol adherence, and tracking and reporting performance must be budgeted.

The actual per-patient compensation to the sites (for enrolling patients and for collecting data) for each trial to be conducted within the network will be provided by separate sources of funding and does not need to be included in this budget. However, the CCC should budget for administrative tasks related to distributing these funds.

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

The budget for the CCC subawards for central pharmacy, central IRB, central laboratory facilities, and any other subawards, should be outlined in the application.

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

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

Leadership and operations plan: The PD/PI should describe in the Approach section of the Research Strategy, how clinical trials and research will be strategically supported by the network Clinical Coordinating Center. The PD/PI should describe the expertise and track record of the research staff, the CCCs SOPs, how tasks will be delegated and supervised, and how the team will communicate. The PD/PI should describe how all aspects of complex multi-center trials will be supported by the CCC. Note that the CCC will be responsible for registering all trials with http://www.clinicaltrials.gov.

Collaboration plan: In the relevant sections of the Biosketch, Resources/Facilities and the Research Strategy or (where applicable), in the Multiple PD/PI Leadership Plan, applicants should describe their ability to work in a collaborative and interactive manner with the Clinical Sites, the Data Coordinating Center, and NINDS and its partners (both academic and industry partners) in all aspects of the network program. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., experience in clinical trial collaborations with industry partners or patient groups). The applicant should indicate how potential network project investigators (from academia or industry) will be motivated to work with the network, supported in the conception phase, and integrated into the network in the planning and implementation phases.

Recruitment and outreach plan: In the Approach section of the Research Strategy, the PD/PI should describe plans for supporting recruitment of patients at the clinical sites, including plans to optimize minority recruitment. Additional details on recruitment plans may be provided in the Recruitment and Retention Plan in the PHS Human Subjects and Clinical Trials Information Form of the application, as appropriate. Prospective recruitment plans should be established for each project and the PD/PI should indicate how outreach into the community at the Clinical Sites, to referring physicians and patients will be encouraged, what actions and materials will be used to support recruitment of patients, and how patients will be included in the conception, planning and implementation of trials so that a strong partnership between investigators and patients can serve as a foundation for successful trial recruitment and retention.

Network-linked conferences for identification and discussion of areas of high unmet need and priority: applicants should describe the plans for organizing the conferences, identification and oversight of subspecialty area focus groups, and plans for generating and executing conference agendas.

Leveraging Local Clinical Research Resources Plan: In the Resources/Facilities section of the application, the PD/PI should describe how local clinical research resources such as equipment, space and research staff will relate to the network CCC activities, and, if applicable, how the network will integrate Clinical and Translational Science Award (CTSA) resources.

Plan to Increase the Quality and Efficiency of the Clinical Research Enterprise at the Clinical Sites: For new trials, describe CCC plans to reduce start-up time by increasing the efficiency of contracting and IRB review through use of standardized master trial agreements and federated IRB models. Describe additional measures in the Research Strategy section that would increase the efficiency of new and ongoing network trials. Describe other plans to increase the quality and efficiency of clinical trials. Describe how protocol adherence and data quality will be maximized in collaboration with the Clinical Sites.

Performance Monitoring and Potential Interventions Plan: Describe how the CCC will monitor performance and collect data on start-up, recruitment and retention, as well as data quality for NINDS-funded clinical trials at the Clinical Sites, for both new and ongoing trials.

Training Plan: The network presents a rich environment for young investigators to be exposed to and develop additional research skills and to assist them in progressing to more senior status. In the Approach section of the Research Strategy, describe the plans to reach out to young investigators.

Clinical Coordination and Project Management Plan:

Leading the network CCC will be a complex and time-consuming undertaking, and applicants must have the necessary experience and expertise to coordinate multi-center clinical trials in pediatric and adult patients with neurological disorders. Therefore, a listing of current and up to five of the most recently completed trials that the CCC applicant has coordinated must also be provided in the 12 page Research Strategy.

The standard operating procedures (SOPs) used by the CCC in the implementation of multi-center clinical trials, including, but not limited to SOPs describing regulatory document collection, IRB approvals, study drug management, procedures to minimize bias and maintain blinding, recruitment plans, retention plans, data sharing plans, safety monitoring plans, etc., should be included under Research Strategy. Plans directly related to participants such as adverse event monitoring, may be included in the Data and Safety Monitoring Plan , as necessary.

In the Research Strategy section, applicants should include a table with a brief description of current and up to five most recently completed trials that the CCC has coordinated, indicating:

• the intervention;
• the funding source;
• the sponsor of the IND;
• any industry partner;
• the drug distribution center;
• the data management center;
• the number and location of sites (US and/or other countries);
• the number of patients;
• the length of follow-up;
• time to first subcontract executed (starting from award date);
• time to last sub-contract executed;
• time to IRB at CCC site;
• time to first IRB approval at any consortium site;
• time to last IRB approval at a consortium site;
• time to first patient screened;
• time to first patient randomized;
• overall recruitment rate;
• gender, race, and ethnicity distribution of the study population;
• proportion of patients lost to follow-up;
• time from last patient last visit to database lock.

Gene Therapy Consortium:

The applicant should describe the composition and structure of the GTC. The consortium should be led by 6-10 members with expertise in gene therapy and gene-targeted therapy, rare and ultra-rare diseases, clinical trial design and execution, and specifically early phase, first in human or first in disease trials. The consortium will be responsible for interacting with selected NeuroNEXT sites, or, if needed, specific sites added on ad-hoc basis if warranted by the need for access to specific patient populations or unique expertise.

The application should detail the expertise and experience of the consortium members in gene therapy and gene-targeted therapy, rare and ultra-rare diseases, clinical trial design and execution, and specifically early phase, first in human or first in disease trials.

Transition plan: The application should include plans for continuing the trials already funded and underway in the network, without significant disruption. The application should also include transition plans for the end of the award period, should the CCC not be selected for funding in the next funding cycle.

Letters of support (LOS): the application should list the LOS providers, and the LOS from intitutional officials, industry collaborators, other stakeholders, should be included LOS section.

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

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA

• In accordance with the NIH policy on appendix materials (NOT-OD-07-018), when a free, online, publicly available journal link in not available, applicants should provide up to 3 manuscripts either accepted for publication or in press that highlight recently coordinated trials;
• One sample protocol and set of Case Report Forms (CRFs).
• For the gene therapy consortium, at least one example of a gene or gene-targeted therapy trial conducted by members of the consortium.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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.

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applications from institutions that have a General Clinical research Center (GCRC) or Clinical and Translational Science Award (CTSA) funded by the NIH National Center for Research Resources should identify in the Resources/Facilities section, the resources that could be available to support the proposed network CCC, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency. In such a case, a description of the GCRC or CTSA and how the applicant proposes interacting with it should be included, as well as letter of agreement (included in the Letters of Support section of the application) from either the GCRC/CTSA Program Director or PI. Having a GCRC or CTSA at the institution is not a requirement for application.

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

• Do the investigators have a track record of working collaboratively?
• Do the investigators have a track record in successfully coordinating multicenter clinical trials?
• Do the members of the gene therapy consortium have experience and expertise in the conduct of gene or gene-targeted therapeutic trials?
• Do the investigators provide consistent evidence for collaborative leadership, and is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA?
• Does the investigator have a successful track record in neuroscience clinical trial coordination?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Are the plans for coordination and execution of clinical trials adequate? In particular, are the plans for managing study start-up conducive to efficiency and reducing delays?

Are the plans for collaboration with other parts of the network and external partners, particularly industry partners, clear and feasible?

Are the recruitment and outreach plans adequate, particularly with regards to recruitment of minorities and under-represented populations?

Is the proposed structure and operation of the gene therapy consortium conducive to efficient and rigorous conduct of trials in ultra rare diseases?

Are the monitoring plans clearly outlined and adequate?

Are the plans for organizing the network-linked open conferences to facilitate stakeholder discussions to identify areas of high unmet need and priority adequate and efficient?

Are proposed interactions/communications between the CCC and the DCC, clinical sites and the community (e.g., referring physicians and patient populations) clearly described and creatively optimized?

Is the applicant’s institution willing to work with a centralized network IRB and through standardized master trial agreements for the per-patient cost of network trials?

Are the transition plans clear 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?

• Does the institution show commitment to the PD/PI by providing departmental and institutional letters that demonstrate support via such means as additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI ?
• Does the application provide assurance that the institution will be able to coordinate and utilize a central IRB of record as well as standardized network master trial agreements for per patient cost of clinical programs?
• Does the applicant have a track record of achieving relatively short trial start-up times with regard to contract negotiations, IRB approval times, study personnel training?

Additional Review Criteria

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

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

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned to NINDS. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDSC) 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.
• Ability to begin operations immediately

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.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.

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

2. Administrative and National Policy Requirements

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

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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

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

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

• Trial participant safety, implementation of network protocols in accordance with GCP and other regulatory requirements, participant recruitment and retention, and reporting to the NINDS, NCC, DMC, and DSMB.
• Recipients 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.
• Center PDs/PIs will be expected to serve on NEC working groups established as needed and charged with tasks such as the development of protocols, submission of clinical trial applications to NINDS for review, publication guidelines, quality assurance monitoring, etc.
• The center PD/PI and coordinator are expected to participate in all network teleconferences and investigator meetings. They are also expected to assist the network NEC in deciding how peer-reviewed research and trial proposals will be selected and prioritized for implementation through the network.

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

• The NINDS staff working with the network investigators will develop performance milestones for centers. Failure to meet the agreed-upon milestones may result in reduced funding or early termination of the cooperative agreement.
• An NINDS Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.
• In addition to the Project Scientist, an NINDS Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
• A separate NINDS Program Official, from the Division of Clinical Research, will serve as the NINDS liaison to the Data and Safety Monitoring Board (DSMB).
• If the proposed trial should require that the FDA issue an IND/IDE, the NINDS Project Scientist and/or Program Official(s) will be present at any meetings held with the FDA related to this NIH-funded protocol.

Areas of Joint Responsibility include:

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

Dispute Resolution:

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

3. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Joan Ohayon, RN, MSN, CRNP, MSCN
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 3014969135
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Section VIII. Other Information

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

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, 2 CFR Part 200, and 45 CFR Part 75.