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 clinical sites 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 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. The objective of the network is to increase the efficiency of clinical research through shared infrastructure for NINDS clinical trials. 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 clinical sites.

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

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.

Clinical Sites will be offered network-approved fee-for-service reimbursement for the per-patient cost from the CCC to implement protocols, according to budgets approved by the SC and NINDS for each protocol. Sites will have the option not to participate in a given trial if they lack the specific expertise or access to specific patient populations, but if participating, will not be able to negotiate the direct costs as funded by NINDS and as approved by the network SC.

Network Projects

This FOA is soliciting applications from centers that have access to patient populations with a variety of neurological disorders. Project proposals from industry and academic investigators are submitted in response to separate announcements, and are selected for funding through the standard NINDS process as outlined in the related announcements.

NINDS expects that at least one project per funding cycle will be targeted to pediatric populations, and it is expected that the studies will target diverse populations.

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. Input will be obtain from patient representatives and patient advocacy groups.

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

Each Clinical Site's Scope of Work includes, but is not limited to:

• Creating and maintaining a clinical site team including an experienced clinical trials expert as site PD/PI and an experienced coordinator who will be responsible for network-wide communications, training, protocol review, and patient recruitment and retention. Applicants are strongly encouraged to include, in addition to the PD/PI, several co-investigators with disease-specific clinical research expertise and access to a clinic population who are interested in working with the PD/PI. At an institution with pediatric and adult patients, the disciplines appropriate for clinical site investigators and co-investigators include pediatric and adult neurologists, neurosurgeons, neuropsychologists, neuroradiologists or other related specialists with a strong interest in clinical research and a wide range of disease interests such as behavioral neurology, neuromuscular disorders, movement disorders, neuroimmunology, or general neurology. These experts may be from the same institution or different institutions.
• Participating in a minimum of four network clinical research projects or trials during the funding period. A Clinical Site PD/PI or any of the potential disease expert co-investigators are encouraged to submit trial applications for peer-review in response to the future Funding Opportunity Announcement for NeuroNEXT projects, and if successful would assume responsibility for being the lead Clinical Site on a given peer-reviewed, network-approved research project, which would entail providing continued leadership in protocol development and implementation in collaboration with the network.
• Implementing shared protocols involving, but not limited to: 1) assembling a local research team, 2) establishing contractual agreements, 3) working with the central IRB on approval and informed consent, 4) recruiting, treating, and following patients according to the study protocols, and 5) collecting and entering accurate, high quality data into the central web-based data management system. To increase the efficiency and reduce start-up time, sites are required to work through standardized master trial agreements agreed to by the network.
• Accurately identifying and recruiting eligible subjects for network studies, and retaining participants throughout the follow-up period as required by protocol.
• Ensuring human subjects' protections and adequate gender and minority representation among subjects enrolled at network Clinical Sites, and ensuring protocol adherence.
• Tracking and reporting trial and performance data to the CCC and/or NINDS on a regular and frequent basis, including recruitment, retention, and adverse events, as required per protocol and by the IRB and regulatory bodies.
• Working with the DCC to ensure complete, accurate, and timely data entry, as well as rapid and complete resolution of any data queries, and to maintain a high level of data quality and completeness. Clinical Site PDs/PIs are also expected to cooperate with monitoring visits and to assist the DCC with the development and implementation of: 1) common data elements, 2) data entry forms, and 3) public dissemination of project results, as needed.

• Helping new clinical investigators develop skills and experience to progress to more senior or experienced status, when appropriate.
• Participating in Network Executive Committee (NEC) meetings and maintaining cooperative interactions with all other Clinical Sites, the CCC, and the DCC in all aspects of the network.
• Assisting the NEC by serving on NEC working groups developed on an as-needed basis, and charged with the planning and implementation of protocols, as well as with recommendations on issues such as publications guidelines, quality control, etc.
• Leveraging local research resources, such as General Clinical Research Center (GCRC) or Clinical and Translational Science Award (CTSA) funded by the National Center for Advancement of Translational Sciences (NCATS), that could be available to support the proposed network Clinical Site. Having a GCRC or CTSA at the institution is not a requirement for application.
• The network presents a rich environment for early stage investigators to be exposed to and develop additional research and clinical trial skills that are critical for pursuing careers in academic clinical research. To support this, each application must include a program that will provide research experiences and career enhancement opportunities to early stage investigators with a required allocated budget of $50,000 in direct costs per year, to be used towards salary support for the selected candidate.
• The site is expected to offer research and career enhancement experiences to candidates who demonstrate potential for independent research careers or who are established investigators and are changing the direction of their research careers, and is encouraged to seek out qualified minorities, women, and persons with disabilities. After an individual is selected, a specific research and career development plan will be developed and facilitated by the leadership of the site, including the research project to be supported by the center. Selected early-stage investigators will be encouraged to pursue other NINDS-sponsored career development awards and fellowships following their NeuroNEXT career enhancement experience.
• Sites are expected to participate, as needed and if required by the details of individual projects, in studies conducted by the Gene Therapy Consortium (GTC).

Network Structure and Management

The NINDS Network for Excellence in Neuroscience Trials includes: one Data Coordinating Center (DCC), one Clinical Coordinating Center (CCC), and 25 Clinical Sites. A network Clinical Site should be able to conduct trials in adult populations, pediatric populations, or both. Special consideration will be given to children's hospitals. Investigators at the NIH Clinical Center may also function as an additional clinical site.

• 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 awardees as NINDS partner, consistent with the Cooperative Agreement mechanism. The NINDS will appoint a Scientific Advisory Board (SAB)has established an External Oversight Board (EOB) for NeuroNEXT. The EOB SAB 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. will review the network Program and advise the network investigators and the NINDS. 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 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.
• 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 Clinical Coordinating Center (CCC) provides overall study coordination, working closely with the DCC and the Clinical Sites. The CCC will coordinate the activities of the NEC, develop and implement investigator and staff training programs and meetings, oversee drug acquisition and distribution as needed, work closely with the project-specific lead protocol teams, support project investigators in IND submission and reporting to the Food and Drug Administration (FDA), establish and maintain standardized master trial agreements with the network sites and distribute funding for network trial projects, maintain regulatory documents and coordinate the central IRB process, support outreach to patients and inclusion of patients in protocol and recruitment plan development, coordinate preparation of manuscripts, and develop operational and publication guidelines within the framework outlined by the network CCC RFA. See companion FOA for more details describing the responsibilities of the network CCC.

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.

Sites will participate in network-linked open conferences to facilitate stakeholder discussions to identify areas of high unmet need and priority. This are organized by the CCC and DCC, and details are available in the relevant FOAs.

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 Clinical Site application per institution (normally identified by having a unique UEI number or NIH IPF number) is allowed.

Awards for a CCC and a Clinical Site may be made to the same institution. However, it is preferable that the CCC and the Clinical Site grant at a given institution be awarded to two 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.

Within the page limits, the following sections should be included:

1) Program overview

2) PD/PI Leadership Plan

3) Collaboration Plan

4) Recruitment and Outreach Plan, including diversity and minority recruitment

5) Plan to Optimize Efficiency of the Clinical Research Enterprise at the Site

6) Performance Monitoring and Potential Interventions Plan

7) Research Experience and Career Enhancement Plan

8). Transition plan for continuation at the end of the funding period (if the site is not selected again)

9) Any specific expertise in gene and gene-targeted therapy, and/or rare disease trials

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 PD/PI for a RCC must document clinical trials expertise with a track record in successfully implementing clinical trials.

Applicants should name, in addition to the PD/PI, co-investigators from neurology and related fields, and within neurology subspecialties. Additional involvement and collaboration with other medical and surgical specialists should be described. Research experience, the availability of research coordinator support and the qualifications of the site coordinator, blood and biological specimen processing and storage facilities, and research pharmacy services should be described in the application. The applicants are encouraged to assemble a diverse team that includes women and minorities.

The availability of pediatric neurology infrastructure and personnel must be described.

A substitute PD/PI candidate must be identified to assure continuity in the event of resignation of the PD/PI. The qualifications and experience of both persons must be described, specifically documenting their respective abilities to organize and manage a center in the network, as well as experience in accruing patients/participants to clinical trials. In addition, the application should describe the strategy used by the PD/PI and Institutional official to delegate leadership responsibility with respect to the trials selected for activation by the network and how the responsibility is delegated among key/senior individuals.

Applicants must identify the career enhancement Director and names of faculty members who will serve as mentors (with a brief description of their research) at their center with their experience in mentoring early stage investigators.

R&R Budget

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

A detailed budget for the Clinical Sites must be presented. The budget should not include Data Coordinating Center or Clinical Coordinating Center costs, costs for investigator meetings, or patient enrollment, treatment or follow-up.

Clinical Site applicants should consider the following issues regarding Clinical Site core budgets. It is expected that the individual Clinical Site will require a minimum level of effort to sustain the organizational aspects of the network. This includes an expected minimum of 1.8-2.25 person months total effort for the leadership (PD/PI); a full-time professional clinical research coordinator over the course of the project period (keeping in mind that protocol funds will include compensation for effort for study personnel on a per-patient/service basis required to execute protocols over and above personnel proposed in the Clinical Site core budget); and travel costs for team members to attend NEC meetings.

Salary included to support research training and career enhancement (with a minimum required allocated budget of $50,000 in direct costs per year for salary support of the training fellow).

The total may not exceed $275,000 direct costs per year in years 1-5 (all of which will be 12-month project years). The release of funds will be milestone-driven, according to milestones to be specified in the Notice of Award. All costs in the proposed budget should include appropriate justification, including details of the resource utilization for the training component. Clinical Sites that do not meet the milestones may be discontinued at the discretion of NINDS, if necessary.

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:

All Applications should include the following in the relevant subsections:

1) Program overview/Progress Report

Relevant Accomplishments. Describe the group’s accomplishments relative to implementing clinical trials according the appropriate situation below:

Currently funded NeuroNEXT sites:Include a report describing the group’s accomplishments relative to participation in NeuroNEXT over the current funding period. This must include:

1. a list of the progress and achievements specific to the application since the previous competitive review.
2. data performance metrics presented in tabular form summarizing performance of their center and/or their satellite facilities contribution to NeuroNext trials. The following metrics below must be included in the table for each NeuroNext trial participated in by this center:

• The start-up time from award to IRB approval;
• The time from initiation of contract negotiation with lead site to contract executed;
• The time from award to first patient screened;
• The time from award to first patient enrolled;
• The enrollment rate;
• The total number of patients enrolled at the site;
• The accrual ethnic, racial and gender distribution
• The proportion of patients lost to follow-up;
• The number of protocol violations at the site.

3. description of timeliness and accuracy of data entry into the network data system;
4. description of team contributions of the site PI leadership, participation in network activities, attendance at meetings, etc.;
5. description of the center’s participation in Educational activities as measured by faculty/fellow presentations and participation (per educational core chairs);
6. description of how the presence of the NeuroNEXT award has facilitated the clinical trial enterprise at the site, and how the site enhanced/strengthened the network.

New Sites Only: Describe the group’s accomplishments relative to implementing neurology clinical trials in the group’s practice setting(s) and provide a detailed summary of the group’s accrual to these trials. Describe the group’s contributions to the research agenda of its affiliated cooperative groups during the past 5 years (if any). This must include efficiency of starting these trials (e.g., time to site activation, time from activation to first patient enrolled, etc.), efficiency of enrollment (e.g., number of subjects enrolled, monthly enrollment rate), and subject retention rate in these studies. Data performance metrics as described above should be presented in tabular form.

2) PD/PI Leadership Plan

The PD/PI should describe, in the Approach section of the Research Strategy, how clinical trials and research at the Clinical Site will be strategically supported by the network Clinical Site PD/PI and coordinator.

As the leader of the site, it is expected that the PD/PI plays a leadership role in some capacity to the community served by the site. The application must describe the leadership role played by PD/PI and other Senior/Key personnel (if applicable) and the impact it would have on the success of their center as well as on the overall network. The application must propose a committed group of multidisciplinary professionals appropriate for its expected clinical trials participation.

3) Collaboration Plan

In the relevant sections, applicants must describe their ability to work in a collaborative and interactive manner with other Clinical Sites, the Clinical Coordinating Center, the Data Coordinating Center, and the NINDS and its partners in all aspects of the network program. Applicants are encouraged to describe any special group expertise or unique strengths of the team as a whole they can offer to the collaborative effort (e.g., team leadership and training, protocol adherence strategies, dissemination activities, recruitment strategies). Applicants must describe the potential pool of co-investigators at the site and their area of expertise. The applicant should indicate how co-investigators will be identified, motivated, and integrated into the network, and how the network team will support the co-investigators. A detailed plan must be included on collaboration with other clinical investigators at the Clinical Site. For sites already in the NeuroNEXT network, a description of the relevant accomplishments in the network, including participation in network committees, is to be included. Details of activities within active studies at the NeuroNEXT site is to be provided in an Appendix (see below).

4) Recruitment and Outreach Plan

Discuss access to a sufficient number of patients to participate in a wide range of neuroscience clinical trials, making reference to specific, objective sources of data on the size of the available population. Sites must include a pediatric neurology component and demonstrate ability to conduct trials in pediatric populations. This is best demonstrated by showing a table that lists by disease the potential co-investigators and their qualifications, track record and interest, as well as the patient population, e.g., total number of patients with the disease seen annually, number of patients currently participating in trials, number of new patients per year for the last full calendar year. Indicate how outreach into the community, to referring physicians and to patients will take place, 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.

Patient access may be accomplished by establishing links with other groups (e.g., other health care providers in the community, such as neurology practices, primary care practitioners, pediatricians, local hospitals, rehabilitation centers, patient support groups, and health maintenance organizations) in addition to the applicant’s institution. If links with other groups are anticipated, the application must include a plan with appropriate letters of support (appended in the Letters of Support section of the application) describing (1) how the applicant Clinical Site will link to and operate with the other groups, and (2) how the Clinical Site will monitor the quality of the other group’s performance (screening, and, if applicable, patient recruitment and data collection).

The application should include a brief description of anticipated problems with recruitment and plans for addressing these problems. Note that proposed solutions to recruitment problems may not include requesting additional funds under this FOA.

5) Plan to Optimize Efficiency of the Clinical Research Enterprise at the Site

Describe plans to reduce start up time of new trials by increasing the efficiency of contracting and IRB review through use of standardized master trial agreements and central IRB. Means to monitor and track performance and to increase recruitment and retention should also be described.

The NIH NeuroNEXT relies on a central IRB and master contract agreement, which are available at https://www.neuronext.org/researchers. Applicant Institutions must state their intent to commit to the use of a master trial agreement and the central IRB coordinated by the network.

6) Performance Monitoring and Potential Interventions Plan

The application must include a plan for how the PD/PI will monitor performance and collect data on startup, recruitment and retention for new and ongoing NINDS-funded clinical trials at the Site. For current NeuroNEXT centers, detail should be included regarding active and past trials.

7) Research Experience and Career Enhancement PlanThe network presents a rich environment for early stage investigators to be exposed to and develop additional research and clinical trial skills that are critical for pursuing careers in academic clinical research. To support this, each application must include a program that will provide research experiences and career enhancement opportunities to early stage investigators. The NeuroNext site is expected to support at least one early-stage investigator annually for a maximum of two years, and must plan on allocating a minimum of $50,000 in direct costs per year toward salary support for each candidate selected. Selected candidates will be expected to spend at least 50% of their time engaged in research or research training activities as part of being an Neuronext fellow. The NeuroNext site must demonstrate a consistent and significant commitment to career enhancement to early stage investigators. The NeuroNext site will be encouraged to select candidates who demonstrate potential for independent research careers and to seek out and include qualified minorities, women, and persons with disabilities. After an individual is selected, a career enhancement plan will be developed through collaboration with the network and facilitated by the leadership of the NeuroNext site. Selected early-stage investigators will be encouraged to pursue other NINDS-sponsored career development awards and fellowships following their NIH StrokeNet career enhancement experience. For a description of these programs, please consult the NINDS training and career development website: http://www.ninds.nih.gov/funding/areas/training_and_career_development/index.htm.

Applicants must describe their center's experience in mentoring clinical fellows in neurology. Applicants should describe their eligible resident pool and their site's history of training fellows in neurological clinical research. Applicants should briefly describe how applications will be solicited (i.e., only at one institution or include neighboring institutions), who will be on the selection committee, and how the candidates will be selected.

Letters of support:

• Include Letters of support from potential co-investigators at the Clinical Site, affirming an interest in collaborating with the potential local network site PD/PI and with the network as such, describing their expertise, track record, interest, and access to patient populations. These should be included in the separate Letters of Support section of the application. The application should include a list of the LOS providers.
• An institutional letter of support from the applicant's departmental and/or institutional leadership: Institutions will be required to document commitment to the PD/PI by providing departmental and institutional support letters, and they are encouraged to demonstrate support via other means (e.g., additional protected time, departmental research leadership position, facilities, space, resources for the PD/PI and/or network center, and how the NeuroNEXT research effort will be given a high priority within the institution (relative to other research efforts and non-NIH supported programs).
• Under Facilities and Other Resources, identify the resources that could be available to support the proposed network Clinical Site, including GCRC or CTSA, facilities for blood and biological specimen processing and storage, research pharmacy services, shared core resources with other networks, repositories, etc. A description of the resource and how the applicant proposes interacting with it should be included, as well as letter of agreement from either the GCRC/CTSA Program Director or PI if applicable.

8) Transition plan

Decribe in detail the plan for continuity of operations in already-funded studies if, at the end of the funding period, the site is not selected again for NeuroNEXT participation.

9) Experience in gene and gene-targeted therapy, and/or rare disease trials

Describe any experience and expertise in the conduct of gene and gene-targeted therapies, and/or clinical trials in rare and ultra rare diseases.

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

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. The following additional instructions apply:

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 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 site, 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 proposed Center address the needs of the research networkthat it will serve? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research network?

For currently funded NeuroNEXT site applications, how significant was the involvement and/or contribution to collaborative activities within the network? How successful was the center in starting and enrolling subjects in clinical trials? How committed was the center’s participation in other network activities?

For new site applications, how relevant are the group’s accomplishments in implementing clinical trials in the group’s practice setting to the goals and requirements for the network?

How will the proposed clinical site contribute to the advancement of clinical research and clinical trials within the framework of the network?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing clinical trial research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

• How adequate is the experience of the applicants team in conducting clinical trials and working together as a group in implementing clinical trials? Is the overall team of professionals participating in the site group appropriate and adequate to achieve the goals and aim of the program?
• Are the qualifications, training, and experience of the PD/PI appropriate for organizing and managing a research program that includes accrual to network-approved trials as well as design and development of clinical trial protocols and research applications? Has the PD/PI demonstrated effective leadership abilities in the community served by the center and/or to the affiliated sites? Have other Key/Senior personnel taken on leadership roles that contribute to the success of the site and/or the research agenda of the affiliated spokes? Does the site coordinator have the adequate qualifications and experience>
• Does the PD/PI have a track record of working collaboratively? Does the PD/PI have a track record in successfully implementing clinical trials? Is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA? Is the investigator willing and likely sufficiently available to participate in network-wide teleconferences, and SC working groups?
• Does the PD/PI have experience and expertise in the conduct of gene or gene-targeted therapeutic trials, and/or clinical trials in ultra rare or rare disease?
• Does the team have expertise and available infrastructure for the conduct of pediatric trials?

Innovation

Does the application propose novel management strategies in coordinating the research projects the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of management strategies proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of 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 site’s plans for implementing network-approved clinical trials well thought out and appropriate for the group’s structure and capacity? Does the application provide evidence that they will establish (new sites) or have established (existing sites) standardized master trial agreements with the network? Are the recruitment/retention plans and outreach plans adequately described and a rationale provided for the likely effectiveness of the plan?

How effective is the existing site group (or new group applicants) in engaging the community served?

Are interactions/communications between investigators at the site and the community (e.g., referring physicians and patient populations) clearly described and creatively optimized? Does the application describe adequate plans to recruit patients with a variety of neurological disorders and with diverse gender/minority representation, as well as plans for human subjects' protection, good clinical practices (GCP)? Is there a track record of patient recruitment and compliance in active or past studies?

Is the career enhancement plan adequate? Does the proposed career development plan describe how promising candidates for independent careers (academic, industrial, governmental) in translational and clinical research will be recruited and selected? Does the proposed plan address how the investigators will seek out and include qualified women and minorities for participation in the proposed training program?

Based on data provided from the current and five most recently completed clinical trials at the site (existing sites must include most recent NeuroNEXT trials the site participated in, or all NeuroNEXT trials participated in if fewer than five), is there evidence to support efficient trial-start up, availability of appropriate patient populations, including under-represented minorities, and success in recruitment, especially with respect to gender and minority recruitment?

Is there evidence that adequate attempts were made to overcome challenges in enrollment in prior trials and were they successful?

Is the transition plan clear and adequate?

Does the center have experience and/or expertise in the conduct of gene and gene-targeted therapies, and/or clinical trials in rare and ultra rare diseases?

Environment

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

• Is there adequate evidence of institutional and departmental commitment to the PD/PI (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI and/or CS)?
• Does the structure appear realistic and is there adequate institutional commitment?
• Are there supporting documents from participating institutions? Are the available facilities, laboratories, in-patient and outpatient resources, and space for administrative activities adequate to support the proposed research activities?
• Is the access to patient populations, adult and pediatric, as well as rare and ultra-rare diseases, adequate for accomplishing the goals of the network?

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

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

Revisions

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.

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 programs 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 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 (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.
• Agreement to accept the Cooperative Agreement Terms and Conditions of Award delineated in this FOA (see Section VI.2.A);
• Geographic balance of Clinical Center awardees;
• Access to pediatric and/or adult patient populations with a wide range of neurological disorders;
• Diversity of study populations among Clinical Center awardees, as well as balance between pediatric and adult populations, and access to minority populations.

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, 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 award's normal scientific and programmatic stewardship 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 awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, 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: 301-496-9135
Email:[email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
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.