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.

No late applications will be accepted for this Funding Opportunity Announcement.

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

The purpose of this funding opportunity announcement (FOA) is to invite applications to participate as a National Coordinating Center (NCC) for the NIH StrokeNet clinical trials network. Established by the NINDS in 2013, the goal of this existing network is to harness the leadership and experience of the stroke research field to maximize efficiencies for developing, promoting, and conducting high-quality, multi-site clinical trials focused on promising interventions for stroke prevention, treatment, and recovery. The network will consider the breadth of cerebrovascular disease beginning with patients identified with acute stroke through stroke rehabilitation and secondary stroke prevention for pediatric and adult patients

Background

Stroke is a disabling, often fatal and expensive disorder that is a major public health burden. Globally it is the second leading cause of death and the third leading cause of death and disability combined. In the United States, stroke has fallen to the fifth most common cause of mortality due to ongoing successes in prevention and acute care, however it remains a costly and leading cause of serious long-term disability. Vascular disease of the brain can manifest not only as overt stroke but also as silent infarction and diffuse white matter disease with cognitive and functional decline. Stroke is a syndrome, with two broad types (ischemic and hemorrhagic) and multiple possible underlying causes. Although stroke impacts all age groups (including children and especially neonates), the incidence is strongly linked to aging but growing at an even faster rate among younger to middle-aged adults. Stroke is projected to become increasingly prominent over the next 30 years, consistent with the rise in the proportion of elderly in the US, and thus will impose an even more significant toll on individuals, families, and society.

NIH-funded basic, translational, and clinical research offers the promise to reduce the burden of stroke.

In 2013, the NINDS established the NIH StrokeNet in response to recommendations from The Stroke Progress Review Group and NINDS stroke planning efforts that identified a need for stroke trial network infrastructure in order to effectively pursue a number of scientific opportunities and to accelerate translation of new potential treatments for patients with stroke and those at risk for stroke (see http://www.ninds.nih.gov/find_people/ninds/OSPP/Stroke-Research-Priorities-Meeting-2012.htm). The network, now completing its second five-year funding cycle, consists of a National Coordinating Center (NCC), a National Data Management Center (NDMC), and two dozen Regional Coordinating Centers (RCCs) located across the United States, each with respective clinical performance sites and satellite sites representing approximately 500 stroke hospitals across the United States.

The NIH StrokeNet was designed to facilitate the development, promotion, and conduct of high-quality, multi-site clinical trials focused on key interventions in stroke prevention, treatment, and recovery and is the primary infrastructure used to conduct all multi-center stroke clinical trials supported by the NINDS. The network includes an education platform designed to train the next generation of stroke clinical researchers and fosters collaborations from a variety of health professionals across multiple disciplines. The interdisciplinary nature of the NIH StrokeNet has been designed to build research capabilities that match the scientific opportunities across the spectrum of stroke research. Additional information on the current structure of the network can be found at: www.nihstrokenet.org.

Research Objectives

The aims of the network are to harness multidisciplinary stroke expertise to collaboratively and efficiently conduct multisite stroke clinical trials. Both large Phase 3 clinical trials as well as exploratory NINDS-sponsored Phase 1/2 clinical trials that can quickly move potential stroke treatments into larger, confirmatory Phase 3 trials, are supported by the network. In addition, the network may perform biomarker validation studies that are immediately preparatory to clinical trial(s) as well as ancillary studies designed to add scientific aims to active studies being conducted within StrokeNet. Collaboration with The International GAINS network (https://www.globalstroketrials.org/) will facilitate the execution of the larger, Phase 3 definitive trials. Together with the larger U.S. and the international stroke research communities, stroke patients, and stroke-related nonprofit associations, the NIH StrokeNet investigators will work to design and execute the most clinically impactful stroke research.

Study execution and performance will be monitored by the NINDS and by the NIH StrokeNet NCC and NDMC to ensure that all eligible stroke patients are considered for NINDS-funded trials.

The NINDS intends that the NIH StrokeNet will be the primary and first-line infrastructure involved in implementing all multi-site stroke trials submitted to the NINDS.

Network Organization

The NIH StrokeNet currently includes: one NCC, one NDMC, and 24 RCCs that have the capacity tocoordinate activities in a large number of Stroke Centers located across the United States. This FOA solicits applications for funding of the infrastructure for the NCC of the NIH StrokeNet. The additional project-specific funds to support the implementation of protocols conducted in the network will come from separate cooperative awards. The NIH StrokeNet is an open network and will consider projects not only from NIH StrokeNet investigators but also from academic investigators outside of the network and in collaboration with small business partners. Collaborative projects developed by site investigators in the network will be strongly encouraged. These funds will be distributed to the RCCs via the NCC on per-patient basis protocol budgets via master trial agreements with the RCCs.

Responsibilities of the National Clinical Coordinating Center include, but are not limited to:

• Overseeing from conception to analysis/publication the implementation of multi-center clinical trials, biomarker validation, and ancillary studies conducted in the network. The number of ongoing studies at any time is dependent upon funding and network infrastructure capacity but may include as many as 20 or more studies at one time.
• Monitoring human subjects' protection and adequate women and racial and ethnic minority representation among subjects enrolled at network clinical sites. The NCC will ensure that studies in the network develop robust community engagement and enrollment plans to ensure broad representation in all funded NIH StrokeNet studies.
• Coordinating all network Steering Committee (SC) activities including, but not limited to, organizing monthly teleconferences and one or two in-person meetings each year, and maintaining documentation such as meeting minutes of SC activities.
• Coordinating scientific working groups in stroke prevention, treatment and recovery represented by RCC membership in the network to develop new protocols, oversee the implementation of approved protocols, and provide in-depth evaluation and recommendations on such issues as publications/presentations, quality control, conflict of interest, per-patient budgets, and others.
• Coordinating network advisory groups that provide oversight of pediatric, endovascular and minority and recruitement in NIH StrokeNet trials.
• Providing leadership and coordination of educational training and activities to junior fellows and research coordinators in the network.
• Including community representation and patient advocates in the working group and operational aspects of the network communication. The NCC will ensure that community and patient representation advises critical aspects of the networks function, and of the development and execution of new trials to be conducted by the network. High level involvement may include representation on the working groups or other leadership groups within the network.
• Leading and participating in the SC discussions and serving on all network working or advisory groups.
• Coordinating and documenting all communication and reporting between the NCC, RCCs, central IRB of record, and local IRBs, which includes but is not limited to maintaining documentation of IRB initial approvals, amendment approvals, adverse events, and other reports. Working with the NDMC and the project PD/PI to provide study data to the NINDS-appointed Data and Safety Monitoring Board (DSMB).
• Establishing standard Master Trial Agreements (MTA's) with the RCCs. Develop and implement a plan to reduce the start-up time of each network project through the use of these standard master trial agreements and distributing the 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, accommodating expiration timelines, and drug accountability.
• Coordinating management of centrally stored neuroimages collected in NIH StrokeNet studies.
• Working with the Project PD/PI and IND sponsor (investigator or industry partner) on obtaining FDA regulatory approval for the trial (IND/IDE or exemption), on reporting, documenting and coordinating follow-up correspondence, and on registering with clinicaltrials.gov.
• Working closely with the NDMC in a collaborative and interactive manner. The NCC and NDMC will jointly develop a Standard Operating Procedure (SOP) to oversee all functions within the network.  This will include a scope of work document that details the division of tasks and responsibilities within the budget 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 NCC and NDMC) be delineated.  It is therefore required that the joint NDMC and NCC 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 each potential new network project, the NCC is responsible for:

• Collaborating with RCC PD/PI's within the network to develop original stroke clinical trial, biomarker validation or ancillary study grant applications for submission to the NINDS for peer review.
• Providing information necessary to potential investigators as they apply for funding by the NINDS (e.g., reviewing protocol synopsis and schedule of activities, creating project work scope and timeline, ensuring 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).
• If needed, the NCC will support project PD/PIs in the IND/IDE submission

During the Planning Phase of approved network projects, the NCC is responsible for:

• Working with a project lead team of investigators to finalize the protocol and consent form.
• Collaborating with the NDMC to create case report forms (CRFs).
• Participating in the selection of additional sites as needed.
• Developing a written, detailed patient recruitment and community engagement plan, with attention to adequate racial and ethnic minority recruitment.
• Monitoring the IRB approval process and promoting rapid approval through a well-developed and complete document at the initial submission, and through rapid and comprehensive responses to any IRB comments or concerns.
• Collecting regulatory documents (1572 forms, curricula vitae, Good Clinical Practice [GCP] certifications, etc.).
• Finalizing details of per-patient payments to sites within approved budgets, developing site payment schedules, and finalizing subcontracts with sites per master trial agreements.
• Finalizing study drug packaging and labeling.
• Holding investigator meetings and ensuring initial study personnel complete training for GCP and protocol adherence.
• Working with the NDMC as they establish a trial database.

During the Implementation Phase, the NCC is responsible for:

• Overseeing the enrollment of eligible subjects.
• Tracking enrollment and retention, developing outreach interventions as needed, and reporting progress to the NINDS.
• Distributing study drug to centers.
• Working with sites to ensure appropriate protocol implementation and adherence to protocol and GCP.
• Answering queries from the centers regarding protocol, drug dose adjustments, adverse events, premature withdrawals, etc.
• Conducting site visits, as needed.
• Supporting the NDMC in their monitoring and data quality assurance procedures. Coordinating activities with SIREN or other international consortia and sites as warranted in the enrollment of subjects into the clinical trial.

During the Analysis and Publication Phase, the NCC is responsible for:

• Assisting the NDMC and network centers 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 NDMC and network investigators in the publication of the primary and, if applicable, secondary manuscripts.

Strategic planning:

New for this funding cycle, the NCC and NDMC will organize, with the collaboration of leadership from the RCCs, a series of at least network-linked, open conferences to facilitate community stakeholder discussions that identify areas of high unmet need and priorities in stroke research. The goal will be to proactively identify areas of unmet need or priorities in stroke prevention, treatment, and recovery in which projects could be proposed to the NINDS for implementation in the network. Leadership at the NCC, NDMC, and RCCs will be encouraged to work with the broader stroke community to prioritize areas of unmet need. Additional support for the meetings will be encouraged through the submission of conference grants to NIH and solicitation of outside sponsorship as appropriate.

National Data Management Center

The NDMC supports protocol data management, ensures data quality control (including data monitoring), and undertakes interim monitoring, analyses, and reporting for the NCC, the NINDS, and Data and Safety Monitoring Boards (DSMB's). The NDMC also initiates and coordinates activities that promote standardization of data elements using the NINDS Stroke Common Data Elements and supports an aggressive sharing policy for de-identified data.

Regional Coordinating Stroke Centers

The RCCs selected for funding in the network will have both clinical science excellence and specialized expertise in stroke management, a strong background in stroke research, and a proven ability to recruit stroke patients that include patients from various racial and ethnic minority groups. Each RCC is expected to have a multi-disciplinary collaboration that includes stroke specialists from neurology, pediatric neurology, emergency medicine, neurosurgery, neuroimaging, interventional radiology, neurointensive care, neurorehabilitation, other medicical specialists, and emergency medical services. RCCs are expected to propose, develop, and conduct protocols, recruit patients, and disseminate research findings. Each RCC will be expected to take part in multiple concurrent protocols and to recruit additional sites into their regional consortium as needed to enroll participants in a timely manner in NINDS-funded NIH StrokeNet trials. All individual RCCs will also be required to participate in a cooperative and interactive manner with one another and with the NCC. Awards may be restricted at sites unable to successfully participate in network protocols, including those with inadequate patient enrollment.

A typical RCC in the network is envisioned as a regional academic medical center or tertiary care facility capable of providing research support for its collaborative stroke centers.  RCCs may choose to include geographically or organizationally linked partners or satellite stroke centers, such as other academic centers and/or private and community hospitals and clinics. Such satellite stroke centers could be venues for additional patient enrollment or might provide access to patient populations not traditionally cared for at the RCC. The RCC will be responsible for providing scientific leadership and regular communication to satellite centers regarding protocols and study progress and for providing administrative and budget support for protocol initiation.  In addition, preclinical stroke activities at the RCCs will contribute to the development of compelling phase 1 and 2 research applications and enhance training opportunities.  All centers will be strongly encouraged to increase the value of clinical research data through aggressive data sharing.

National Institute of Neurological Disorders and Stroke

The NINDS will be responsible for organizing and providing overall support for the network. The NINDS Division of Clinical Research and the NINDS Grants Management will be responsible for the overall management of the network. In addition to regular grant stewardship, a NINDS Project Scientist will be involved substantially with the recipients as a NINDS partner and co-chair on the network's leadership committees, consistent with the Cooperative Agreement mechanism. The NINDS maintains the NIH StrokeNet DSMB that monitors all network trials and the External Oversight Board (EOB), comprised of an external group of experts, who reviews the network program and provides feedback to network investigators and the NINDS on a bi-annual basis.

Network Committees

1. The Executive Committee for the network consists of the Program Director/Principal Investigator (PD/PI) of the NCC (who will serve as a co-chair), the NINDS Project Scientist (who will serve as a co-chair), the PD/PI of the DMC, co-PI's from the NCC and NDMC, and selected PD/PI's and Research Program Managers from the RCCs. The Executive Committee will provide strategic network leadership and overall network management. It is anticipated the Executive Committee will meet by video conference call on a bi-monthly basis.

2. The Steering Committee (SC) consists of the PD/PI's of the NCC and NDMC, the NINDS Project Scientist, and the PD/PI or their designees from each of the network RCCs. The SC will be the main governing body for the network's scientific operation and conduct. All major decisions will be determined by majority vote of the SC. It is anticipated that the SC will meet at least monthly by conference call and 1-2 times per year in-person. Recipients will be required to accept and implement policies approved by the SC.

3. The Operations Committee for the network consists of the PD/PI of the NCC (who will serve as the chair), a co-PI/PD, if designated, the PD/PI of the NDMC, the NINDS Project Scientist and/or Program Official and selected PD/PI's or their designees from the RCCs. The Operations Committee will oversee all the network's operational activities (including MTA's, Reliance Agreements (RA's), and other agreements) and monitor trial performance. It is anticipated that the Operations Committee will meet by conference call on a weekly basis.

4. Working Groups for stroke prevention, treatment, and recovery, imaging and training cores, and advisory committees for ethics and competing trials, racial and ethnic minority recruitment and retention, interventional management, and pediatric stroke comprised of members from the coordinating centers, each of the RCCs and community patient representation perform a variety of functions, such as but not limited to:

• Contributing to the development of network stroke trial applications for grant submission.
• Developing protocol concepts.
• Finalizing protocols for funded studies.
• Reviewing the feasibility of trial applications submitted to the NINDS from both inside and outside the network.
• Facilitating the execution of newly-funded or on-going NINDS-funded stroke trials.
• Training and storage of imaging studies in network trials.
• Educational and mentoring programs for RCC fellows.
• Developing strategies for inclusion of women,racial/ethnic minority and children recruitment.
• Producing and submitting publications.
• Developing per-patient budgets.
• Assuring quality control.
• Monitoring conflicts of interest.
• Developing data sharing policies.

5. The Career Development and Training Committee will ensure the network provides consistent and centralized education to enhance the professional development, training, and mentoring of future leaders in stroke research. This committee will assist in organizing mentorship and training of NIH StrokeNet fellows at all the RCCs nationwide. Education will be designed to enhance the developmement of network fellows, program managers and research study coordinators across the network to ensure the robust development of future stroke researchers.

Independent of the governance above, the NINDS Director retains responsibility for all NINDS-funded research. The Director's authority overrides any decision made by the network.

Network Projects

Over the next 5-year project period, the network will continue to conduct a robust portfolio of NINDS-funded NIH StrokeNet Phase 2 and Phase 3 trials and biomarker validation and ancillary studies that are at various stages of nearing completion or just being initiated (http://nihstrokenet.org/clinical-trials/trials). NINDS expects that additional protocols will continue to be developed to complement and replace current studies with the exact number dependent upon the nature and extent of the investigations proposed and the availability of funds. Projects proposed to and conducted through the network may come from the collaboration of investigators within and outside of the network using the NIH StrokeNet funding announcement PAR-20-285 (UG3/UH3).

Transition plan:

If the currently funded NCC is not chosen in this competition, then the current NCC application must include a transition plan to a new NCC. This transition plan must include a description of the processes needed for a new NCC to access all and any materials from the current NCC.

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 Grants.gov registration; 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. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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 NCC application per institution (normally identified by having a Unique Entity Identifier or NIH IPF number) is allowed. 

Investigators at the NCC institution are strongly encouraged to also apply for a RCC award.  However, NINDS expects that the NCC and a RCC at the same institution be led by separate PD(s)/PI('s) to ensure that the NCC activities as well as the local RCC activities receive full attention.

Awards for a NCC and a NDMC will not be made to the same PD/PI or to the same institution to ensure that data analyses and data acquisition are performed independently.

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:

Catherine Levy, RN
National Institute of Neurological Disorders and Stroke (NINDS)
Phone: 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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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.The following additional instructions apply:

The PD/PI for the NCC will be a clinical trials expert with a track record in successfully coordinating and implementing multicenter stroke clinical trials:

• Applicants must have demonstrated leadership in the design and conduct of clinical trials in stroke prevention, treatment, and recovery, as well as a track record in successfully coordinating and implementing multi-center stroke trials, and working with academic, foundation and industry partners.
• Applicants must describe their specific experience with international trials.
• Clear leadership from various areas of stroke research must be evident in the NCC application.  Applicants must list, in addition to the PD/PI, identified co-investigators from neurology, interventional neurology, neurosurgery, emergency medicine, neurointensive care, neuroimaging, neurorehababilitation, and pediatric neurology who have collaborative willingness to participate in trials conducted in the network.  Co-investigators from preclinical stroke laboratories should also be identified for their ability and willingness to contribute to the leadership and activities of the overall network.  The applicants are encouraged to assemble a broadly diverse team, consistent with NOT-OD-22-019, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities. .
• Applicants are strongly encouraged to name an experienced research team that will support the project management and implementation of the network trials, and to list additional clinical research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution.

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 NCC must be presented.  The budget must include all activities delineated in the list of NCC responsibilities included in this FOA necessary to manage the current ongoing NIH StrokeNet trials and for developing future trials to be conducted within the network.

Budget requests may include the following allowable items:

• Support for the PD/PI's salary for time spent on organizational/administrative NCC tasks.
• Salary for program directors, educational core activities, and business administration.
• Support for imaging core activities; chairs of the working groups; advisory core to increase minority recruitment and retention in NIH StrokeNet studies ; and participation of patient survivors or advocates in network leadership activities.
• Support for administrative personnel or study assistants.
• Network meetings, SC, and other leadership committee functions.
• Site visits.
• Communication, documentation, and reporting required to operate or manage a central IRB of record.
• Study drug management and pharmacy staff.
• Collecting and administering contract and regulatory documents.
• Start-up activities.
• Working with potential network investigators in the protocol conception development and implementation phases.
• In addition, administrative tasks related to subcontracting with clinical sites, monitoring recruitment and protocol adherence, and tracking and reporting performance must be budgeted.
• The budget should also include travel costs for core NCC team members to attend SC or operational core meetings, DSMB meetings, and Network-linked open conferences to discuss areas of unmet need and priorities.

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 should not be included in this budget.  However, the NCC should budget for administrative tasks related to distributing these funds.  

The release of funds will be milestone-driven, according to milestones pre-specified in the Notice of Grant Award. 

R&R Subaward Budget

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

The budget for the NCC subawards including central pharmacy, central IRB, central laboratory facilities, and any other subawards, etc. 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:

Research Strategy: The Research Strategy should include the following:

A) Leadership Plan

The PD/PI must describe how stroke trials and research will be strategically supported by the NCC. The PD/PI should describe the expertise and track record of the research staff, the NCCs 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 NCC.

B) Collaboration Plan and Communications Plan

Applicants must state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with the RCCs, the NDMC, and the 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 advocacy groups) and their history and experience in submitting stroke clinical trial applications to the NINDS.  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.  Applicants must also demonstrate their ability to establish strong collaborative relationships between vascular neurology, emergency medicine, interventional neuroradiology, neurosurgery, neurointensive care, neuroimaging, stroke rehabilitation, and pediatric neurology.  Applicants must also indicate their willingness to attend all network investigator meetings, weekly and bi-monthly network trial operational meetings and network working group and advisory meetings.

C) Recruitment and Outreach Plan

The PD/PI should draw from their own experience to describe plans for supporting recruitment of stroke patients at the clinical sites, including plans to optimize the recruitment of racial and ethnic minority participants. Additional details on recruitment plans may be provided in the Human Subjects section of the application. Prospective recruitment plans must be established for each project and the PD/PI should indicate how outreach into the community at the clinical sites and to referring physicians and patients will be encouraged, as well as 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.

D) Leveraging Local Clinical Research Resources Plan

The PD/PI must describe how local clinical research resources such as equipment, space, and research staff will relate to the NCC activities, and, if applicable, how the network will integrate Clinical and Translational Science Award (CTSA) resources.  In such a case, a description of the General Clinical Research Center (GCRC) or CTSA, and how the applicant proposes interacting with it, should be included, as well as a letter of agreement from either the GCRC/CTSA Program Director or PD/PI included in the “Letters of Support” section of the application.  Having a GCRC or CTSA at the institution is not an application requirement.

E) Plan to Increase the Quality and Efficiency of the Clinical Research Enterprise at the Clinical Sites

Applicants must discuss their (and their institutions') willingness and experience to establish master trial agreements with each RCC, so that the per-patient cost associated with specific network protocols can be efficiently administered.  Applicants and their institutions must also indicate their willingness to coordinate a single IRB model or how they will manage and outsource to a commercial signal IRB.  If applicable, describe additional measures that would increase the efficiency of ongoing NINDS-funded clinical research, even if outside of the network.  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.

F) Performance Monitoring and Potential Interventions Plan

The application must describe how the NCC will monitor performance and collect data on start-up, recruitment, and retention, as well as data quality at the RCC and the stroke center sites for all NINDS-approved trials that are are or will be conducted within the NIH StrokeNet.

G) Training and Career Enhancement Program

The network presents a rich environment for clinical fellows or junior faculty interested in stroke clinical research to be exposed to and develop additional research skills that will assist them in progressing to more senior status. Additionally, the network also provides an opportunity to foster growth, mentorship and career development of research study coordinators and program managers. The applicant must describe their centers experience in the training and mentorship of fellows, program managers, and research study coordinators and describe a plan for how the NCC will organize and coordinate an NIH StrokeNetwide education and career development training program for early carrer fellows, program managers, and research study coordinators at each of the NIH StrokeNet RCCs.  Lastly, applicants should identify any unique resources or opportunities that could further the training effort of fellows trained at funded sites within the network.

H) Clinical Coordination and Project Management Plan

Leading the NCC is 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 stroke. Therefore, a listing of current and up to five of the most recently completed trials that the NCC applicant has coordinated must also be provided.

Applicants should describe the SOPs they have in place and the processes they currently apply when coordinating multi-center projects. Applicants are encouraged to provide examples of SOPs used by the NCC 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., as an appendix to the application.  Plans directly related to participants such as adverse event monitoring, may be included in the Human Subjects section as necessary.

In this section, applicants should include a table with a brief description of current and up to five most recently completed NIH trials that their center has coordinated, indicating:

• the intervention.
• the sponsor of the IND.
• 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 IRB at clinical coordinating center site.
• time to first IRB approval at any consortium site.
• time to first patient screened.
• time to first patient randomized.
• overall recruitment rate.
• proportion of patients lost to follow-up.
• time from last patient last visit to database lock.

I) Contribution to potential future network trials

Applicants should describe how the NCC will promote awareness of NIH StrokeNet and stimulate the submission of grant applications for future clinical trials.   Applicants should discuss specific actions and how this will be managed during the next funding cycle.  Investigators awarded a NCC grant will be required to provide a record of their contributions on each annual progress report of its collaboration to bring meritorious trials into the network including special populations such as pediatric studies.

J) Strategic planning:

Applicants must describe plans for how they will work with leadership within the network as well as scientific leaders outside of the network, to organize one to two network-linked, open conferences during the next funding cycle designed to facilitate community stakeholder discussions that identify areas of high unmet need and priorities in stroke research. Plans may include how they will help obtain additional support for the meetings; this support may include the submission of conference grants to the NIH and solicitation of outside sponsorship as appropriate.

K) Transition plan

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

Letters of Support:

A statement of commitment from each participating institution or organization to the PD/PI that demonstrate how the institution or organization will support the PD/PI's efforts to manage the NIH StrokeNet National Coordinating Center functions and activities must be provided.  Additionally, provide a cover page in the application listing the names and institutions of all letter of support providers.

• At least one letter of support from the applicant's institution must be included in the application.  This letter should address how the institution will maintain accountability for promoting scientific excellence and how the NIH StrokeNet effort will be given a high priority within the institution (relative to other research efforts and non-NIH supported programs.) The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the NCC director, assignment of specialized research space, cost sharing of resources, and/or other ways proposed by the applicant institution.  Institutions should document their willingness to use master trial agreements and a central IRB. If the Institution is committing facilities or resources to create, maintain or support the central IRB and/or master contracts, these should be presented in detail.  There may be multiple letters of support from the institution or its components, particularly if the institution is providing support of collaboration for specific NCC responsibilities, such as the central IRB or master contracting. At least one letter confirming institutional support should come from a high-level institution official(s) (e.g., Dean of the School of Medicine, Hospital President, and Vice President for Research).
• If the central IRB will be in collaboration with the institutional IRB or a duly constituted independent IRB, the application should include a letter of support from the IRB chair. The letter should include any specific commitments of facilities or resources by the IRB (e.g., regulatory consultants, record storage space, computer software). If the proposed central IRB is an institutional IRB, senior institutional leadership should include the central IRB in their letter of support.  
• Additional letters of support are encouraged from key personnel and consultants, such as the proposed IRB chair, physician investigators, experts in recruitment or other NCC responsibilities or emergency care experts.  
• For those institutions that have a GCRC or CTSA award funded by the NIH National Center for Research Resources the applicants are encouraged to include documentation from either the GCRC/CTSA Program Director or PI regarding how the resources could be available to support the proposed NCC, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency, and what specific support is provided.  Having a GCRC or CTSA at the institution is not an application requirement.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• A Data Management and Sharing Plan is 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.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

• In accordance with the NIH policy on appendix materials (NOT-OD-07-018), when a free, online, publicly available journal link is not available, applicants may provide up to 3 manuscripts either accepted for publication or in press that highlight recently coordinated trials;
• Applicants should provide sample documents that illustrate the NCC's expertise, such as policies, manual of procedures, etc.
• Applicants should provide one sample study SOP 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.

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

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

Section V. Application Review Information

1. Criteria

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

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?

Specific to this FOA:

Does the proposed NCC address the needs of the NIH StrokeNet clinical research program that it will coordinate? Is the scope of activities proposed for the NCC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the clinical research network?

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?

Specific to this FOA:

Do the PD/PI(s) have a track record and demonstrate an ability to work in a highly collaborative setting?  Is there assurance that the proposed research team and administrative personnel are qualified, capable and experienced?  Do the applicants have a track record in successfully coordinating multicenter stroke trials?  Do the applicants demonstrate a strong relationship between neurology, emergency medicine, interventional neuroradiology, neurosurgery stroke rehabilitation, and pediatric neurology?  Do the applicants have a track record in successfully implementing and completing stroke clinical trials?  If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; is their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the CCC?

Do the PD/PI(s) and their research team have appropriate experience to manage a central IRB? Do the applicants have the experience needed to execute NIH StrokeNet financial management responsibilities (e.g., master trial agreements, budgets)?

How appropriate are the expertise and personnel incorporated into the NCC and/or provided by the institution?

Do the applicants have a track record of developing and submitting stroke clinical trial grant applications to the NINDS? Do the applicants describe how they will work with the network to propose new clinical trials to the NINDS?

In what ways does the application suggest that the PD/PI can lead and contribute substantially to the NIH StrokeNet governance committees (e.g., NIH StrokeNet Executive Committee, Steering Committee, Operations Committee, and working groups)? Does the application demonstrate that the PD/PI will have time to attend the meetings and teleconferences? Is there evidence of experience in and willingness of the various stroke-related services to participate appropriately in a collaborative program as described in this FOA?

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?

Specific to this FOA:

Are interactions/communications between investigators at the institution clearly described and creatively optimized?  Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the NCC will serve? Are the strategies to ensure a robust and unbiased scientific approach across the network appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented?

Are the applicants sufficiently available and are their plans adequate to participate in network-wide meetings, teleconferences, SC, and working groups? Do the applicants have a track record for successfully initiating and completing large, multisite clinical trials and studies and in what way do these metrics support that the applicants would form an exemplary NCC for coordinating and executing clinical trials and clinical studies in the network? In particular, are the plans for managing study start-up conducive to efficiency and reducing delays? Is an appropriate plan for work-flow and a well-established timeline proposed? Does the application demonstrate awareness and include adequate and realistic planning, including plans for community outreach, for achievement of racial and ethnic minority and women enrollment. Are the overall plans and infrastructural support at the proposed NCC for patient recruitment and enrollment, including feasibility assessments, trial specific recruitment plans and other components outlined in Research Plan well described and sufficient to contribute to the success of the NIH StrokeNet? 

In what ways does the application provide assurance that the proposed NCC will provide strong organizational focus for the NCC itself and for the NIH StrokeNet?

Does the application show strong concern for and adherence to high quality standards? Does the application propose a plan for quality assurance and quality improvement for the NCC itself and for the NIH StrokeNet infrastructure (NDMC. RCCs) which will produce an exemplary and successful network?

To what extent does the application demonstrate that the proposed NCC will meet the challenges of flexibility and scalability required to meet the needs of the different clinical trials to be conducted in NIH StrokeNet

Are the plans for collaboration with other parts of the network and external partners, particularly industry partners, clear and feasible?  In what ways will the applicants ensure adequate collaboration and information sharing: 1) with the NDMC; 2) with clinical sites (RCCs, satellites, ad hoc performance sites, pre-hospital providers); 3) with clinical trial PIs? In what ways does the communication plan provide assurance that the CCC will continue to provide sufficient procedural training and will provide rapid, accurate resolution of questions/issues?

Does the applicant show a commitment to training early-career fellows, research study coordinators, and program managers, and does the application include plans for how the NCC will organize and coordinate a network-wide education and career development training program?  Does the application include plans for organizing network-linked open conferences that will facilitate stakeholder discussions to identify areas of high unmet need and priority?

Does the applicant have a track record of achieving relatively short trial start-up times with regards to contract negotiations, IRB approval times, and study personnel training? Are there plans for how the applicant and the institution will continue to support the trials already funded and underway in the network without significant disruption, and for how transition to a new NCC will occur if the current NCC is not selected for the next funding cycle?

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?

Specific to this FOA:

Does the institution show commitment and provide reasonable plans to the PD/PI through 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? Are the plans and assurance provided by the institution adequate and reasonable to be able to coordinate and utilize a central IRB of record as well as standard network master trial agreements for per-patient cost of clinical programs? 

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

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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 the 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.

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

Applications will be assigned to the NINDS. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council. The following will be considered when 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; Agreement to accept the Cooperative Agreement Terms and Conditions of Award delineated in this FOA (see Section VI.2).

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 will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. 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 providing program access, reasonable modifications, and to provide effective communication, 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 religious nondiscrimination laws and 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 award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 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 resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Coordinating all aspects of network research protocols, including monitoring trial participant safety, implementation of network protocols in accordance with GCP and other regulatory requirements, participant recruitment and retention, reporting to the NINDS, and working with the NDMC in reporting to the DSMB and to clinicaltrials.gov.
• 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.

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

• A NINDS Project Scientist will 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 the NCC. Failure to meet the agreed upon milestones may result in reduced funding or early termination of the cooperative agreement.
• In addition to the Project Scientist, a 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) for all network trials or studies.

Areas of Joint Responsibility include:

• A network Executive Committee will consist of the PD/PI of the NCC (who will serve as a co-chair), the NINDS Project Scientist (who will serve as a co-chair), the PD/PI of the NDMC, co-PI's from the NCC and NDMC, and selected PD/PI's and Research Program Managers from the RCCs. The Executive Committee will provide strategic network leadership and overall network management.
• A Network Operations Committee will consist of the PI/PD of the NCC (who will serve as the chair), a co-investigator., if designated, the PI/PD of the NDMC, the NINDS Project Scientist, the NINDS Program Official, and selected PD/PI's (or their designees) from the RCCs.  The Operations Committee will centrally monitor all the network's activities.
• A Steering Committee (SC) will consist of the PD/PI's of the NCC and NDMC, the NINDS Project Scientist, and the PD/PI's or their designee from each of the RCCs.  The SC will be the main governing body for the network and its scientific operation and conduct.
• The NCC PD/PI and other key staff are expected to participate in all network teleconferences, trial operation meetings, and investigator meetings. They are also expected to serve on SC working groups established on an as-needed basis to develop and oversee specific protocols, and to provide in-depth evaluation and recommendations on such issues as publications/presentations, protocol implementation, quality control, conflict of interest, and others.

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 will be convened. The panel will have three members: a designee of the SC 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 recipient. 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. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. 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: https://www.era.nih.gov/need-help (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: 301-480-7075

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

Scott Janis, Ph.D.
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: nindsreview.nih.gov

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 and 45 CFR Part 75.