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 Data Management Center (NDMC) for the NIH StrokeNet stroke trials network. Established by 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 selected for funding in response to the current soliciations/seperate FOAs 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 to coordinate activities in a large number of Stroke Centers located across the United States. This FOA solicits applications for funding of the infrastructure for the NDMC 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 a per-patient basis protocol budgets via master trial agreements with the RCCs.

Responsibilities of the National Data Management Center include, but are not limited to:

1)  Data Management

• Maintain a network NDMC Standard Operating Procedures (SOPs) for all aspects of data management used in the current network.
• Adhere to a scope of work plan developed in collaboration with the NCC that clearly delineates NCC and NDMC tasks, respectively, and document communication plan.
• Identify an experienced data management team that is expected to include an experienced computer programmer and project manager.

During the Conceptual Phase of a new network project, the NDMC is expected to:

• Provide information and/or collaborate with RCC PD/PIs within the network to develop original stroke clinical trial, ancillary projects, or biomarker validation grant applications for submission to the NINDS.
• Provide information and/or collaborate with potential investigators or companies outside of the network as they apply for NINDS funding (e.g., review protocol synopsis and schedule of activities, create project work scope and timelines for database building).

During the Planning Phase of approved network projects, the NDMC will:

• Work with the project lead team of investigators to finalize data management aspects of the protocol.
• Work with the project investigators and NCC to create a database for each trial in a timely manner.
• Develop Case Report Forms (CRF's).
• Finalize randomization scheme/process.
• Develop a data quality assurance plan.
• Develop a data monitoring plan.

During the Implementation Phase of approved network projects, the NDMC will:

• Support all data management aspects of trials implementation including but not limited to:
  • Build on existing hardware and software infrastructure and experience to maintain a web-based, user-friendly database for each trial.
  • Incorporate security features consistent with U.S. DHHS guidelines, including but not limited to secure, password protected database access, and audit trails for database changes.
  • Implement procedures for backing up the program’s clinical and administrative data, including intermittent duplication of the database with storage at a remote facility.
  • Protect patient confidentiality at all steps in the submission and analysis of clinical trials data and ensuring the technical integrity and security of the data management systems.
  • Provide in a timely manner data and reports at the request of the DSMB, the FDA, or the NINDS.
  • Provide true copies of data files and supporting documentation for all network-supported protocols in a timely manner.
  • Support web-based or other mode of central randomization.
  • Support Electronic Health Record and other electronic data intregration.
  • Provide documentation of drug distribution in collaboration with the NCC.
  • Establish quality assurance procedures for data quality and completeness.
  • Answer database questions and resolve technical issues for database users.
• Provide efficient project management for data management projects.
• Promote standardization and harmonization of data collection across trials to include using the NINDS Stroke Common Data Elements (CDE).
• Work with the NCC to report and track trial status in terms of enrollment and retention.
• Transfer data to statistician and others for interim analysis as needed, and at the end of follow-up, cleaning, and closing-out the database.

2)  Data Quality Assurance

• Oversee data quality control, including but not limited to regular data queries and data monitoring and cleaning to assure data completeness and quality.

3)  Data Sharing

• Support and promote rigorous data sharing after trial completion by preparing a final data set, with limited personal or de-identified health information, in a format appropriate for data sharing, for submission to a secure data repository after publication of the primary study results, or after 18 months, whichever comes first.

4)  Communication

• Work with the NCC and RCCs to support study communication, including, but not limited to an investigator communication platform/website where the study documents (i.e., protocol and amendments, the manual of procedures, and other study communications) are stored.
• Provide staff with training and answer questions regarding database use.
• Work with the NCC to ensure that trial status and results are posted on ClinicalTrials.gov, as required.
• Work with the NCC, RCCs, and network project teams, to create a public website platform for recruitment and outreach efforts for all network projects.

5)  Monitoring

• Identify an experienced data monitor to conduct at least annual site visits to monitor the quality of record keeping, source documentation, and the accuracy of data entry.

6)  Statistical Support

• Identify at least one experienced statistician, with a documented track record in successfully designing and implementing clinical trials in stroke (i.e., exploratory Phase 1, 2 and Phase 3 trials).
• Include expertise in adaptive, Bayesian, or innovative statistical methodology necessary to provide statistical input into the potential design of adaptive Phase 2/3 clinical trials that could be done within the network, or expertise in using innovative adaptive methodology to assist in the design and/or analysis of studies that could efficiently compare multiple approaches or interventions.
• Provide statistical input to network investigators or to potential network project applicants at the request of the NINDS during the conceptual, pre-submission phase.
• Collaborate with the clinical investigators and project study statisticians in the oversight of interim and final analyses per protocol and in preparation of presentations of primary and secondary publications.
• Provide additional analyses at the request of the DSMB, the FDA, or the NINDS.
• For network trial applicants who already have an established and successful working relationship with a statistician in the field of the application, the NINDS may allow for his/her participation; this project-specific statistician will have to be willing to and will have to describe a plan to work closely with the NDMC team and lead statistician in a collaborative manner and under a pre-specified statistical leadership plan.

7)  Collaborating with Other Network Components

• The NDMC PD/PI will be a member of the Operations Committee and the Network Steering Committee (SC).  The NDMC PD/PI and team will work with PD/PIs and statisticians of network projects selected for funding during the protocol development and planning phase. The NDMC PD/PI and team will work with the project specific SC during the implementation and analysis/publication phase.  The NDMC PD/PI will be responsible for ensuring data quality in the network studies.
• The NDMC will work closely with the NCC in a collaborative and interactive manner.  The NDMC and NCC – once selected for potential funding – will submit to the NINDS jointly their respective SOPs, revised from the version originally submitted with their applications, based on their jointly developed collaboration plan. They will also submit a scope of work document detailing the division of tasks and responsibilities within their proposed budget.  Before the award is made, the NINDS will review the joint SOP and scope of work documents for approval.  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 NDMC and NCC) be delineated.  It is 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.

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 Coordinating Center

The NIH StrokeNet NCC will work closely with the NDMC and the 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, distribute funding for network trial projects, maintain regulatory documents, 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.

Regional Coordinating 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 includes a strong track record of including patients from various racial and ethnic 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 Phase 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, an 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 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. 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 Master Trial Agreements (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 NCC, NDMC, 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 the recruitment of women and racial/ethnic minorities .
• 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 that 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 targeted to both network fellows and research 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 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 NDMC is not chosen in this competition, then the current NDMC application must include a transition plan to a new NDMC. This transition plan must include a description of the processes needed for a new NDMC to access all and any materials from the current NDMC.

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

Awards for a NDMC and a RCC may be made to the same institution.  However, it is expected that the NDMC and the RCC grants at a given institution be led by separate PD(s)/PI(s) and preferably in different departments or distinctly separate locations within the institution.

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: levyc@mail.nih.gov

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 PD/PI for the NDMC will be an experienced statistician and clinical trial data management expert, with a track record in successfully implementing the statistical and data management aspects of multicenter stroke clinical trials.

• Applicants should have demonstrated leadership in successfully coordinating and implementing multi-center stroke clinical trials, working with academic, foundation, and industry partners.
• Applicants should describe their specific experience with international trials.
• Applicants should describe their experience with designing and/or conducting stroke clinical trials testing interventions in prevention, treatment, and recovery.
• The PD/PI must be available to attend all network investigator meetings, which may include conference calls 1-2 times a month and in-person meetings at least 1-3 times each year.

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 research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution.  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. .

R&R or Modular Budget

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

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

• Planning activities.
• Start-up activities.
• Randomization support.
• Implementation activities.
• Close-out phase activities.
• Participation in investigator meetings, SC, and other leadership committee functions.
• Data and quality assurance monitoring.
• Communication, documentation, and reporting.

The budget should also include travel costs for approximately 2-3 trips each year for core team members to attend SC meetings in Bethesda, MD, and other travel related to network operations (including at least one visit per site and funding period).

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 should include the following:

A) Leadership Plan

Applicants must describe how stroke trials and research will be strategically supported by the NDMC. The application must describe the prior leadership experience and expertise and experience of the research staff, the NDMC's SOPs, how tasks will be delegated and supervised, and how the team will communicate. The applicants must describe how all aspects of complex multi-center trials will be supported by the NDMC.

B) Collaboration 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 NCC, and the NINDS and its partners (both academic and industry partners) in all aspects of the network program.  Applicants must describe their plans for communications with the NCC and clinical sites within the network. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., established database tools, hardware, software, quality control tools, monitoring expertise, team leadership and training, communications platforms, website design and management).  Applicants must also indicate their willingness to attend all network investigator meetings, which will include conference calls one or two times a month and in-person meetings at least one or two times a year.

C) Data Management, Quality Assurance and Monitoring Plan

Based on the tasks outlined above, the PD/PI must describe how the data management, quality assurance and monitoring programs for network projects will be supported, building on existing strengths. A data management system should:

• Collect data in a user-friendly manner, with a user interface directed at the experience and knowledge of users (rather than that of programmers, data managers or statisticians).
• Collect data in a manner appropriate to the source of data (i.e., data collected by people should be entered by people, data generated by machines should be imported from the machine, data generated in a lab should be entered by the lab, etc.).
• Integrate data from Electronic Medical Records and other disparate electronic data sources seamlessly.
• Validate data as thoroughly as possible on collection and/or entry.
• Validate data completely, on an ongoing basis.
• Have a rigorous error and query resolution process, which monitors data quality throughout the collection process.
• Allow for the easy dissemination of data to statisticians and other analysts, in a variety of tab delimited formats.
• Allow for the easy production of regular reports on trial status and progress.
• Have graduated, role-based security or newer data security methods, which permits varying degrees of access to data based on an individual’s role in the study.
• Protect any collected personal health information (PHI) from unauthorized access, and create a log of all authorized access.
• Assemble all study data in a well-documented central store, to facilitate data sharing and dissemination.

D) Statistical Support Plan

Based on the outline above, the PD/PI must describe how all statistical aspects of trials, from the planning phase through study completion, will be supported.  The PD/PI should describe how a non-NDMC statistician would be integrated into network NDMC operations of their project.  Under this scenario, the project statistician leads the statistical design, analysis plans, and the final analysis for publication, while remaining blinded during the course of the trial. The NDMC statistician leads the data management and preparation of unblinded reports and analyses. As warranted during the development of new study protocols both statisticians will work together to ensure the design is suitable for implementation through the network. The applicant should outline the expertise of the NDMC in Phase 3 trials, exploratory Phase 1 and Phase 2 clinical trials and adaptive designs. Additional experience in designing biomarker validation studies should also be included.

E) Plan to Increase Data Sharing Opportunities

According to the goals and tasks outlined above, the PD/PI must describe how standardization and harmonization of protocols, data collection, and data collection instruments will be promoted, including the integration of the NINDS stroke common data elements. The PD/PI should describe how datasets of completed trials will be submitted for data sharing to a NINDS repository, using data exchange standards.  The PD/PI should also describe their ability or collaborations that could support a bio-imaging repository within the network.

F) Trial Start-up and Participant Recruitment

Participation in the network will be a complex and time-consuming undertaking. Therefore, the applicant must include a description of current and up to five of the most recently completed NIH trials that were coordinated by their data management team, along with a detailed record indicating the following, in a table or bulleted format:

• The start-up time for each trial in terms of establishing a database and other tools (including CRFs and randomization mechanism).
• Time from last patient's last visit to database lock.
• Time from database lock to final primary analysis.
• In addition, the application should include the following information.
  • A description of data management system/software the applicant uses currently or proposes to use for this network should be provided in the Resources/Facilities section of the application.
  • A description of data sharing procedures.
  • Published manuscripts that highlight recently coordinated trials should be referenced in the biosketch or literature cited section of the application.

G) Project Management and Coordination Plan

Applicants must describe the SOPs they have in place, and the processes they currently apply when implementing multi-center clinical trials in stroke.  Applicants are encouraged to provide an example of a SOP used by the NDMC in the implementation of multi-center clinical trials, including, but not limited to SOPs describing database access, data quality control, data queries with audit trails, etc., as an appendix to the application. 

I) 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 NDMC 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 Data Management 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 NDMC director, assignment of specialized research space, cost sharing of resources, and/or other ways proposed by the applicant institution. There may be multiple letters of support from the institution or its components, particularly if the institution is providing support of collaboration for specific NDMC responsibilities. 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).
• 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 sub-specialists.

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:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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-17-098), when a free, online, publicly available journal link is not available, applicants should 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 NDMC's expertise such as CRFs, data dictionaries, user manuals, database training instruments etc.
• Applicants should provide a sample study MOP describing the NDMC's database access, data quality control, data queries with audit trails, 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 NDMC address the needs of the NIH StrokeNet clinical research program that it will coordinate? Is the scope of activities proposed for the NDMC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the NIH StrokeNet 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:

Dothe PD/PI(s) have a convincing track record in successfully designing and implementing the statistical and data management aspects of multicenter clinical trials in neurological disorders and stroke? Does the application indicate that the PD/PI and research team have the appropriate experience to successfully lead, design and implement the data management and statistical components of multicenter clinical trials and biomarker validation studies to be performed in the NIH StrokeNet?Are the PD(s)/PI(s) and other personnel well suited to their roles in the NDMC? Do they have appropriate experience and training and have they demonstrated experience and an ongoing record of accomplishments in managing clinical research in 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 NDMC?

In what ways does the application suggest that the PD/PI can contribute substantially to the NIH StrokeNet governance committees (e.g., Executive committee, Steering Committee, Opertions Committee, Working Groups, etc.)? Does the application demonstrate that the PD/PI will have time to attend the meetings and teleconferences?

In what ways will the experience of the proposed research team and administrative personnel increase the likelihood that performance will be exemplary at the proposed NDMC?

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 the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the NDMC will serve? Will the applicants 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? Are an appropriate plan for work-flow and a well-established timeline proposed?

Are interactions/communications between the NDMC and the NCC, clinical sites, and the community clearly described and creatively optimized? Are the investigators likely to carry-out key tasks in a timely manner, including, but not limited to establishing the database, data cleaning, analysis, and data sharing?

Do the investigators provide consistent evidence for collaborative leadership in statistical and data coordination of multicenter trials, and is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA? Do the applicants have a track record of working with clinical PI's to develop and submit stroke clinical trial grant applications to the NINDS? Is there evidence that the applicants will work with the network PI's and PI's outside of the network to propose new clinical trials to the NINDS? Is there a plan by the applicant that describes how a non-NDMC statistician would be integrated into NDMC operations for their project?

In what ways does the proposed data management system achieve the characteristics of a desirable system? How well does the plan achieve the goals of making a user friendly system that minimizes burden on clinical trial sites (e.g., can digital data be imported from laboratory data bases and/or machines)? How robust are the data validation and query systems? Does the application ensure plans for data security and intergration of Electronic Heath Records and other electronic Data?

In what ways does the application demonstrate that Risk Based Monitoring will be used to optimize generation of clean accurate, high quality clinical trial data while minimizing monitoring time, particularly on-site monitoring time?

In what ways does the application demonstrate that the NDMC has the required knowledge, experience and an appropriate plan for submitting de-identified, widely useable data bases to the data repository in a timely fashion at the conclusion of each clinical trial?

In what ways does the communication plan promote collaboration and information sharing: 1) with the NCC; 2) with clinical sites (RCCs, sateliites, performance sites, ad hoc sites, etc.); 3) with clinical trial PDs/PIs? In what ways does the communication plan provide assurance that the NDMC will provide sufficient procedural training and will provide rapid, accurate resolution of questions/issues?

In what ways does the application provide assurance that the planned administration and organization of the NDMC itself, and the quality assurance program will lead to exemplary NDMC performance and contribute to the success of the NIH StrokeNet?

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 to the PD/PI(s) by providing departmental and institutional letters that demonstrate support via such means as additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI? Are there plans for how the applicant and institution will continue to support the trials already funded and underway in the network without significant disruption, and also for how transition will occur if the current NDMC is not selected for the next funding cycle?

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, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The NDMC 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 NCC 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 NDMC. 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, a 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 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 NDMC 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scott Janis, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email: janiss@ninds.nih.gov

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

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

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.