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), issued by the NINDS, is to invite currently awarded NIH StrokeNet centers and potential new stroke centers to participate as a Regional Coordinating Stroke Center (RCC) in 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 NINDS stroke planning efforts (https://www.ninds.nih.gov/stroke-research-priorities-meeting-2012) 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 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 NIH StrokeNet-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 to coordinate activities in a large number of Stroke Centers located across the United States. This FOA solicits both currently awarded network centers and new center applications for funding of infrastructure for RCCs in 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 industry 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.

Expectations of the Regional Coordinating Centers

To be selected as an RCC in the NIH StrokeNet, the center must demonstrate both clinical science excellence and specialized expertise in stroke management, a strong background in stroke research, and a proven ability to recruit patients who have had a stroke  from various racial and ethnic groups for participation in stroke clinical trials and clinical research project. 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, and other medical 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 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 that are unable to successfully participate in network protocols or provide adequate patient enrollment.

All NIH StrokeNet RCCs and their satellites and performance sites are expected to be committed to working with and agreeing to their reliance on a single review of their research activities by a central IRB which is facilitated through the NCC. Responsibilities of the central or single NIH StrokeNet IRB include initial review, continuing review, and review of all amendments, deviations, and noncompliance issues for all multi-site protocols initiated within the network. Additionally, the central IRB will be responsible for Conflict of Interest (COI) review and management as well as approval of informed consent documents and processes. Local IRB responsibility will include review of site-specific context, including local laws, institutional policies, local context and COI local review and management. Efficiencies gained by the single IRB review are essential for the streamlined execution of multi-center clinical research projects in the NIH StrokeNet. Additionally, RCCs will be expected to agree to a master trial agreement with the NCC to distribute all trial-related payments. Additional information on the current agreements can be found at: www.nihstrokenet.org/documents.

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 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 clinical research applications, and also enhance training opportunities. 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. The NCC will manage ongoing operational issues, such as subcontracts for capitated payments, protocol-specific site training, and site monitoring. The productivity of the partners and satellites will be considered part of the RCCs contribution to the NIH StrokeNet.

RCCs will also be committed to the education and career development of clinical fellows or junior faculty interested in stroke clinical research. Working with the NIH StrokeNet training program directed by the NCC, RCCs will support at least one StrokeNet trainee annually to develop an individualized educational career enhancement program that exposes them to, and helps them develop, additional research skills, and that assists them in progressing to more senior status. Additionally, leadership in the RCCs will also be committed to providing mentorship and career development of research study coordinators and program managers both at their RCC and at their satellite or performance centers. New to the NIH StrokeNet in this next renewal period will be the addition of an Education and Development Program for program managers and research study coordinators that will be centrally run by the NCC and supported by the RCCs; its aim will be to build a robust resource of trained research managers for the future.

National Clinical Coordinating Center

The NIH StrokeNet NCC (being solicited for the next funding cycle through RFA-NS-23-009) will work closely with the NDMC and RCCs to provide overall network coordination and project management that support the principal investigators of each NIH StrokeNet study. The NCC will coordinate the activities of the steering committee, 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 regulatory IND (Investigational New Drug) or IDE (Investigational Device Exemption ) submission and reporting to the Food and Drug Administration (FDA), establish and maintain standardized master trial agreements with the RCCs and distribute funding for network trial projects, maintain regulatory documents and coordinate the central IRB process, monitor eligibility of participants, assure compliance with regulations and monitor the informed consent process, prepare blinded reports on adverse events, monitor study execution at sites, support outreach to patients and inclusion of patients in protocol and recruitment plan development, supervise and encourage recruitment, coordinate editorial and manuscript preparation, and develop operational and publication guidelines within the framework outlined by the network NCC FOA. The NCC will also coordinate the development of clinical trial protocols as well as the clinical budgets to be submitted to the NINDS for peer review for future execution in the NIH StrokeNet. In addition, the NCC will collaborate with the NDMC in developing and implementing data management procedures.

National Data Management Center

The NDMC (being solicited for the next funding cycle through RFA-NS-23-008) 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 (DSMBs). 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.

National Institute of Neurological Disorders and Stroke

The NINDS will be responsible for organizing and providing overall support for the network. Staff within 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 awardees 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 the 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 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. It is anticipated that 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. Awardees 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 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 Master Trial Agreements (MTA's), Reliance Agreements (RAs), and other agreements) and monitor trial performance. It is anticipated that the Operations Committee will meet by conference calls 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, the recruitment and retention of minorities and women as study participants in NIH StrokeNet studies, interventional management, and pediatric stroke, comprised of members from the NCC, NDMC, and each of the RCCs 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 to ensure representative recruitment of women and minorities as study participants.
• Producing and submitting publications.
• Developing per-patient budgets.
• Assuring quality control.
• Monitoring conflicts of interest.
• Developing data sharing policies.

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 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).

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

Awards for a RCC and a NCC may be made to the same institution. However, it is preferable that the NCC and the RCC grant at a given institution support two different investigators, to ensure that the NCC activities as well as the local RCC activities receive full attention.

Awards for a RCC and a NDMC may be made to the same institution. However, investigators on the RCC award are not permitted to have any role in the NDMC award to ensure that the NDMC activities as well as the local RCC activities are independently managed.

A RCC may be from a single institution or may include geographically or organizationally linked partners or satellite sites, such as other academic centers and/or private and community hospitals and clinics as needed to fulfill the research requirements; however, it is preferable that only one principal investigator be identified for the RCC application.

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.

While the Research Strategy is limited to 12 pages, it should be divided into the following sections:

A. Program Overview

B. Research Program

C. Leadership

D. Training and Career Enhancement Program

E. Administrative Core

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.

A statement of commitment from each participating institution or organization and/or documentation of consortium arrangements must be provided.

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 trial expertise that shows a track record in successfully implementing and conducting stroke clinical trials.
• Applicants should identify a research coordinator or project manager with experience in managing stroke clinical trials and in training additional managers who join the team.
• Applicants must provide a list, in addition to the PD/PI, of identified co-investigators from neurology, emergency medicine, interventional neurology, neurosurgery, neurointensive care, neuroimaging, neurorehab, and pediatric neurology who have collaborative willingness to participate in trials conducted in the network.  Additional involvement and collaboration with other medical and surgical specialists as well as ambulance systems should be described, both for the primary site institution and the proposed satellites (if applicable).  Research experience, the availability of research coordinator support, blood and biological specimen processing, storage facilities, and research pharmacy services must be described in the application.  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.

  .
• 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 RCC in the network, as well as experience in accruing patients/participants to clinical trials.
• Applicants must identify the career enhancement director and provide the names of faculty members who will serve as mentors at their center, along with a brief description of the mentor's research and their experience in mentoring clinical fellows in stroke.

R&R Budget

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

Budget requests may include the following allowable items:

• Partial support for the PD/PI's salary but ONLY for time spent on site organizational/administrative tasks.
• Salary for research coordinators or project managers. The budget should include salary for at least 1 full-time manager at the RCC site; as needed support for program managers may be allowed for high volume satellites that are part of the RCCs network.
• Support for administrative personnel or study assistants.
• Travel to meetings directly related to study activities (e.g., research base meetings, NINDS or network-sponsored strategy sessions/workshops, local travel).
• Special personnel resources needed to support the recruitment and retention of eligible patients on clinical trials.
• Stroke 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 following items are NOT allowed in the budget requests:

• Costs of clinical care provided to patients (e.g., for patient care reimbursement, transportation costs).
• Clinical and Data Coordinating Center costs.
• Physician compensation (other than specified above for PD/PIs and for their network-related administrative activities).

The release of funds will be milestone-driven, according to milestones to be specified in the Notice of Award. RCCs that do not meet the milestones may be terminated, if necessary.

R&R Subaward Budget

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:

Research Strategy:

The Research Strategy must consist of the following Sections A-E.

NOTE: An application from a currently funded NIH StrokeNet RCC (i.e., renewing application) must include a progress report under sub-section A –Program Overview.

A. Program Overview

Background and Experience. Describe the group’s history and experience in conducting stroke clinical research studies, in particular, cooperative group clinical trials and studies supported by the NINDS/NIH over the last 10 years. The application must include a list or table specifically listing the groups experience/participation in acute treatment trials, primary or secondary prevention trials, recovery or rehab trials, and epidemiological/observational studies, as well as the groups enrollment and lost to follow-up rate in those studies. If the group specifically contributed enrollment in the NIH COVID clinical trials ACTIV4-A, ACTIV4-C,  DISCOVERY (Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery) or DIVERSE VCID (Diverse Vascular Contributions to Cognitive Impairment and Dementia) observational studies, this information should also be included. Lastly, the application must provide details that show experience working together as a group, particularly in implementing clinical trials in stroke and related activities.

Catchment Area. The application must delineate its catchment area. Include a description or map of the service area, designating counties or zip codes from which approximately 80 percent of the patients will be drawn.  Particular attention should be given to underserved populations in proximity to the institution and a description of community outreach plans used by the center to ensure an adequate enrollment of populations that experience health disparities (e.g., study tools, training, outreach, community engagement, types of sites or specialties needed, etc.).  A description of the study population in the application’s catchment area, with a breakdown by percentage of the gender and racial and ethnic minority composition(see https://grants.nih.gov/policy/inclusion.htm), should be provided.

Organizational Structure. The application must describe the current and/or planned organizational structure under which it proposes to operate. If the RCC has more than one component/affiliate institution, describe the relationship of component(s)/affiliate(s) to each other and to the RCC. Include the distance between these institutions (including administrative office and shared resources) and location of proposed personnel. All satellite and clinical performance sites considered as part of the RCCs organizational structure should be included.

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

• Currently funded NIH StrokeNet RCC. Include a progress report describing the group’s accomplishments relative to participation in NIH StrokeNet over the current funding period (i.e., 5 years).  This must include:
  1. a list of the progress and achievements specific to the renewing RCC since the previous competitive review.
  2. data performance metrics presented in tabular form summarizing performance of their RCCs contribution (defined to include all enrolling clinical sites as described in the organization structure above) to NIH StrokeNet trials/studies they have participated in including all trials initiated within the network since it was established in 2013 (NIH StrokeNet trials). The following metrics below must be included in the table for each NIH StrokeNet trial/study participated in by this RCC:
     • time from site notification (defined as when the site received the cIRB packet) to site activation (defined as released to enroll study participants)
     • time from site activation to first subject enrolled in the trial/study
     • the total number of subjects enrolled and subjects randomized into the trial/study
     • the average monthly enrollment rate of subjects in the trial/study
     • for studies that include a two-step process for enrolling subjects into the trial/study, the number of enrolled subjects consented for screening eligibility prior to randomization in the trial/study
     • the retention rate of all subjects enrolled in the trial/study
     • percentage of CRFs submitted into the NDMC web data system within the protocol required time window
  3. a description whether or if new satellites were added that improved performance of the RCC and how they were selected or whether or if underperforming satellites were dropped and how that effected their RCC performance.
  4. a description of whether or how performance at the center was impacted by the pandemic and solutions implemented to restore function of the RCC to their pre-pandemic efficiency.
  5. a description of contributions of the RCC PI leadership to national network activities (i.e., working groups, educational core, advisory committees, program manager groups, etc.).
  6. a description of the RCCs participation in educational activities which may include their trainees' engagement in NIH StrokeNet training (such as abstracts, papers, grant applications, presentations at NIH StrokeNet and national meetings, clinical trial enrollment, etc.); careers of former trainees (i.e., academic positions, publication record, grant submissions, etc.); and RCC engagement (e.g., membership in Education and Training Core, Learning Community leader, mentorship of trainees, lecturer/moderator for Grand Rounds webinar, Professional Development webinar, Basic Science webinar, etc.).

• New Applications only. Describe the group’s accomplishments relative to implementing stroke clinical trials in the group’s practice setting(s) and provide a detailed summary of the group’s accrual to these trials including contributions from their satellite and clinical performance sites.  Describe the group’s contributions to the research agenda of its affiliated cooperative groups during the past 5 years (if any). This should 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.  If the applicants institution or their proposed RCC satellite sites are currently enrolling study participants in one of the ongoing NIH StrokeNet trials (NIH StrokeNet trials) as a non-NIH StrokeNet or NIH StrokeNet satellite site, they should include performance metrics for that trial in the application.  Data performance metrics as described above should be presented in tabular form.

B. Research Program

The application must describe the group’s plans and approach for implementing and conducting NIH StrokeNet clinical trials (NIH StrokeNet trials) in the practice setting(s) of the community it serves and how the RCC will support and ensure high performance for the satellites in their RCC consortium.  The plans should cover the next 5 years. The plans must include a description of how the RCC will access a pool of patients representing various racial and ethnic groups to meet or exceed accrual requirements and/or planned accrual goals and how they will work with their satellites to ensure they have adequate support and leadership to be a contributing clinical site in all NIH StrokeNet studies.

Applicants must state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with other RCCs, the NCC and NDMC, and the NINDS and its partners in all aspects of the network program.  Applicants are encouraged to describe any special team expertise, or unique strengths of the team as a whole, that they can offer to the collaborative effort (e.g., team leadership and training, protocol adherence strategies, dissemination activities, and 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 outreach and collaboration with other clinical investigators at the RCC, because the success of the network will depend on collaboration with co-investigators who have protocol-specific clinical research expertise. 

Applicants must indicate their willingness to work within the network to propose timely clinical trials.  Investigators supported by an RCC grant to the network will be requested to provide a record of their contributions on each annual progress report; continuation of support may rely partially on its collaboration to bring meritorious trials into the network.

To demonstrate their capabilities or potential future contributions to the NIH StrokeNet, applicants should include a brief paragraph that describes how they could contribute (i.e., development, design, leadership, expertise, etc.) to potential future trials in stroke prevention, treatment, and recovery.  Applicants should specifically address involvement and potential contributions from preclinical stroke laboratories and researchers at their institutions.  Additionally, they should comment on their capacity for pediatric studies.

Applicants should indicate their willingness to attend all network investigator meetings, which will include conference calls at least 1-2 times a month and in-person meetings at least 1-2 times a year.

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 potentially also for ongoing NINDS-funded clinical trials at the RCC and any applicable satellite sites.

C. Leadership

 The application must 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. 

As the leader of the RCC, it is expected that the PD/PI plays a leadership role in some capacity to the community served by the group.  The application should 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.

A mentoring plan or program for leadership succession within the site is recommended to ensure a smooth transition of leadership if, and when it is necessary, and should be described in the application.

The application must propose a committed group of multidisciplinary professionals appropriate for its expected participation in NIH StrokeNet clinical trials. This team should include experts from emergency medicine, neurology, neurointensive care, physiatry, neuroradiology, neurosurgery, interventional neuroradiology, pediatric neurology and subspecialists, with variations depending on local circumstances, as appropriate.  The success of the overall network will be enhanced by advice and input from preclinical basic and translational stroke investigators.  Collaborators at the network site who have special expertise in stroke biology and might contribute to the development of Phase 1 and Phase 2 clinical trial grants should also be identified.  A description of the RCC team, how they operate and interact with each other and with their satellites and how they lend their special expertise to achieve the goals of the RCC, as well as to the success of the overall network, should be provided.

D. Training and Career Enhancement Program

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.  The RCC is expected to support at least one early-stage investigator annually and should 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 NIH StrokeNet fellow, including attending NIH StrokeNet grand rounds, professional development webinars, journal clubs, etc. offered through the NIH StrokeNet training core at the NCC. The RCC must demonstrate a consistent and significant commitment to career enhancement for early-stage investigators in stroke research.  The RCC will be encouraged to select candidates who demonstrate potential for independent research careers and to recruit prospective candidates from broadly diverse backgrounds 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..  After an individual is selected, a career enhancement plan will be developed through collaboration with the network and facilitated by the leadership of the RCC.  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 stroke.  Applicants should describe their eligible resident pool (e.g., number of stroke, emergency, interventional, etc. residents) and their site's history of training fellows in stroke 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.

New to the NIH StrokeNet in this next funding period will be the addition of a Program Manager and Research Coordinator Education and Development Program coordinated by the NCC and aimed at building a robust resource of trained research managers for the future. RCC applicants must state their commitment to providing mentorship to their RCC program managers and research study coordinators (both for managers and study coordinators at the RCC site as well as at their RCC satellites) and to support the development of program managers and/or research study coordinators at other RCCs, especially those that are new to the network.

E. Administrative Core

Operations: The application must describe the RCCs standard operating procedures and plans for how the workflow is implemented for activating trials, accruing and following participants/patients, retaining patients, and collecting and managing the data associated with the trials and trial accrual.  It should describe the hierarchy the center has in place to oversee the day-to-day operations for conducting clinical trials.  It should also describe the plans for communication among physicians and component/affiliate institutions as well as incentives for participation in clinical trial accrual. Finally, the qualifications, experience, and proposed duties of all proposed support personnel should be described.

Data Management & Quality Assurance: The internal quality assurance plan and procedures of the RCC must be described. Assurance of quality is the joint responsibility of the center and its affiliated satellite stroke centers.  Procedures for data collection and investigational drug monitoring must be described in the application.  For data management procedures, include details on the following: who is responsible for data management overall; what is the source of records (e.g., hospital, office, clinic, registry); who will register patients on trials; how will the information flow; who will enter data on primary patient records and study forms (e.g., nurses, physicians, data managers, secretaries); who will collect and send patient materials (e.g., pathology slides, port films, etc.) to the centers if required; and what systems are in place for electronic data transfer and integration and management of Electronic Health Records.

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 Regional 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 RCC director, assignment of specialized research space, cost sharing of resources, and/or other ways proposed by the applicant institution. 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).
• The letters of support should provide evidence of willingness to accept NIH StrokeNet procedures coordinated by the NIH StrokeNet NCC specifically including: 1) standardized master trial agreements; 2) per-patient payments: 3) centralized trial budgeting; and 4) using a central IRB of record. It should also demonstrate a willingness to work with a central IRB on EFIC clinical trials.

• A statement of commitment to participate in NIH StrokeNet should be provided from for the satellite and performance sites that are included in the RCCs network. These letters should include description of particular resources to be committed, relevant prior experience, planned organizational and/or administrative structure in conjunction with the Hub, and willingness to participate collaboratively in the broader NIH StrokeNet structure (e.g., central IRB, master contracts).

• 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.

• Additional letters of support may be included from key personnel, such as disease experts and physician subspecialists.

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.

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 proposed Center address the needs of the research network that 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?

Specific to this FOA:

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

How will the proposed RCC contribute to the advancement of clinical research and clinical trials within the framework of the NIH StrokeNet?

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 stroke 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?

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 demonstrate a strong relationship between neurology, emergency medicine, interventional neuroradiology/neurosurgery and neurorehabilitation that will support their RCCs participation in large number of NIH StrokeNet trials?  Does the PD/PI have a strong track record in successfully implementing stroke clinical trials?  How robust/stong is the experience in, and willingness of, the various stroke-related services and preclinical stroke laboratories to participate appropriately in a collaborative program as described in this FOA? How robust/strong is the experience of the applicant's team in conducting stroke clinical trials and working together as a group in implementing clinical trials?  Is the breath of the overall team of professionals participating in the site group appropriate and adequate to achieve the goals and aim of the program? Does the application include a reasonable/satisfactory transition plan to replace the primary PI/PD if and when necessary inthe event of resignation of the PD/PI? Does the application demonstrate a commitment to recruit prospective staff and faculty from diverse backgrounds?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research network 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 organizational concepts, management strategies or instrumentation 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?

Specific to this FOA:  

Are interactions/communications between investigators at the RCC and between their satellite and performance sites clearly described and creatively optimized?  Does the RCCs past performance and descriptions of the RCCs future roles in potential clinical trials indicate that the site is likely to be a productive contributor to the overall network? Are well thought-out cogent plans in place for the RCC to provide support and leadership to their satellites and performance sites in their RCC consortium? Does the RCCs past performance demonstrate the experience and willingness to do a range of stroke trials?  Is the patient population (within their RCC consortium) large enough, and do the physicians affiliated with the proposed site see enough patients to ensure that the site will be able to meet or exceed the accrual requirements in the network-approved clinical trials?  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 experience and willingness that they will establish standardized master trial agreements with the NCC? Does the application demonstrate awareness and include adequate and realistic planning, including plans for community outreach to achieveadquate women and racial and ethnic minority representation. . And is there evidence that their recruitment/retention plans and community outreach plans are sufficient to contribute to diverse enrollment in NIH StrokeNet trials and studies?  How effective is the existing site group (or new group applicants) in engaging the community they serve?  Are the affiliations of the RCC with their satellite stroke centers well described and adequate to support the successful performance of this RCC?  Does the proposed plan for career enhancement describe how candidates who show promise for independent careers (academic, industrial, governmental) in stroke research will be selected? Does the RCC applicant provide their commitment to the mentoring and development of RCC program managers and research study coordinators at their RCC and in the network?

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?

Specific to this FOA:

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)?  Does the application indicate willingness of the institution to commit to a single review of their research activities by a single central IRB and to master trial agreements coordinated by the NCC for all NIH StrokeNet projects?  Does the RCC provide evidence of commitment from their proposed satellite and performance sites and is the evidence adequate to support their successful contribution to the NIH StrokeNet efforts?  

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

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 resources 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.
• Wide geographic diversity of the network.

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 Part 75 and 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 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 RCC PD(s)/PI(s) will have primary responsibility for:

• Defining research objectives and approaches.
• Planning, conducting, analyzing, and publishing results, interpretations, and conclusion of their studies and for providing overall scientific and administrative leadership for the Research Project.
• Supervising the clinical study with consistent emphasis on collaborative interactions between investigators, advisory and steering committees, and NINDS representatives.
• Interacting with the NIH StrokeNet NCC, the NIH StrokeNet NDMC, as well as NIH StrokeNet RCCs and any ad-hoc sites.
• Acting as a member of the NIH StrokeNet SC for the duration of the study, with possible participation in steering groups for planning, quality control, capitation, publications etc.

In addition:

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

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

• 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.
• The NINDS staff working with the network investigators will develop performance milestones for the RCCs. Failure to meet the agreed upon milestones may result in reduced funding or early termination of the cooperative agreement.
• 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 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 recipients 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 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200– 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: [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 and 45 CFR Part 75 and 2 CFR Part 200.