NIH StrokeNet Clinical Trials and Biomarker Studies for Stroke Treatment, Recovery, and Prevention (UG3/UH3 Clinical Trial Optional)

NIH StrokeNet Clinical Trials and Biomarker Studies for Stroke Treatment, Recovery, and Prevention (UG3/UH3 Clinical Trial Optional) is sponsored by National Institute of Neurological Disorders and Stroke (NINDS), NIH.

This funding opportunity encourages applications for multi-site exploratory and confirmatory clinical trials focusing on promising interventions; biomarker or outcome measure validation studies preparatory to trials in stroke prevention, treatment, and recovery; and ancillary studies within NIH StrokeNet. Successful applicants will collaborate and conduct the study within the NIH StrokeNet infrastructure.

PAR-25-052: NIH StrokeNet Clinical Trials and Biomarker Studies for Stroke Treatment, Recovery, and Prevention (UG3/UH3 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and Funding Opportunity Title NIH StrokeNet Clinical Trials and Biomarker Studies for Stroke Treatment, Recovery, and Prevention (UG3/UH3 Clinical Trial Optional) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose This NOFO encourages applications for multi-site exploratory and confirmatory clinical trials focused on promising interventions; biomarker or outcome measure validation studies that are immediately preparatory to trials in stroke prevention, treatment, and recovery; and ancillary studies designed to add scientific aims to active studies being conducted within StrokeNet.

Successful applicants will collaborate and conduct the study within the NIH StrokeNet . Following peer review, NINDS will prioritize studies among the highest scoring to be conducted in the NIH StrokeNet infrastructure.

The NIH StrokeNet National Coordinating Center (NCC) will work with the successful applicant to implement the proposed study efficiently and the National Data Management Center (NDMC) will provide statistical and data management support. The NIH StrokeNet Regional Coordinating Centers (RCCs) and their affiliated clinical sites will provide recruitment/retention support as well as on-site implementation of the clinical protocol.

The NIH StrokeNet network will also be uniquely poised to collaborate with other US and international consortia necessary to conduct larger, definitive trials of promising interventions for stroke treatment, prevention, and recovery. It is NINDS's intent that all NINDS-supported multi-center clinical trials in stroke treatment, recovery, or prevention will be conducted within the NIH StrokeNet.

Only in exceptional circumstances will NINDS consider funding multi-site stroke clinical trials outside of this network. This NOFO uses the bi-phasic, milestone driven UG3/UH3 cooperative agreement activity code. Awards made under this NOFO will initially support a one-year milestone-driven planning and start-up phase, with possible transition to an implementation (UH3) phase of up to 6 additional years.

Only UG3 projects that meet the scientific milestones and award requirements of the UG3 phase may transition to the UH3 phase. Applications submitted in response to this NOFO must address both the UG3 and UH3 phases and are expected to include plans for project management and performance milestones for each phase. Applicants do not need to be part of the existing NIH StrokeNet infrastructure to apply under this NOFO.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) 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.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description To facilitate the cooperation and partnering of public and private funding organizations, universities, academic medical centers, research institutes, contract research organizations, biotechnology companies, and pharmaceutical companies in the advancement of interventions for stroke prevention, treatment, and rehabilitation, NINDS formed the NIH Stroke Clinical Trials Research Network ( NIH StrokeNet ) .

The NIH StrokeNet comprises a National Clinical Coordinating Center (NCC), a National Data Management Center (NDMC) and 27 geographically distributed Regional Coordinating Centers (RCC) which involve approximately 500 affiliated stroke centers in the United States.

Studies conducted within the NIH StrokeNet network encompass the breadth of cerebrovascular disease, including treatments of acute stroke, stroke rehabilitation therapies, and primary and secondary stroke preventions for pediatric and adult patients. The network provides a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of NINDS-funded stroke trials.

The network's infrastructure is designed to increase the efficiency of stroke clinical trials by facilitating patient recruitment and retention, supporting novel methodologies and streamlined approaches to accelerate the development of promising stroke therapies, and enabling comparisons between approaches. NINDS has established the NIH StrokeNet to facilitate and streamline the execution of clinical trials in stroke.

Thus, it is expected that all multi-center clinical trials for stroke treatment, prevention, and recovery supported by NINDS will be considered for implementation through the NIH StrokeNet.

This NOFO provides the primary opportunity for the submission of applications for multi-center exploratory and confirmatory stroke clinical trials focused on promising interventions, including pragmatic trials performed in large numbers of patients with minimal alteration from clinical practice and low per-patient costs.

Exploratory clinical trials must include a clearly defined pathway, with go/no-go decision points to guide advancement to a future Phase 3 trial. Also eligible for support under this NOFO are biomarker- and outcome-validation studies that are immediately preparatory to trials in stroke prevention, treatment, or recovery, as well as ancillary studies designed to add scientific aims to active studies being conducted within StrokeNet.

It is NINDS’s intention that NIH StrokeNet will maintain a balanced portfolio of studies in each of these three areas, defined as follows: Primary and secondary prevention stroke trials – studies of agents, devices, or strategies to prevent recurrent stroke in survivors of stroke or transient ischemic attack (TIA), or to prevent first stroke in high-risk populations.

Emergent management or acute stroke treatment trials – studies of agents, devices, or strategies to intervene during the acute phase of stroke with the goal of reducing brain injury and promoting optimal patient recovery. This may include pre-hospital as well as emergency department or in-patient approaches and includes all stroke types.

Neuro-recovery and rehabilitation stroke trials – studies of agents, devices, or strategies to improve long-term recovery, including cognitive, behavioral and/or motor function or quality of life outcomes, and/or to reduce the time to optimal recovery in patients after the acute period.

The use of innovative and efficient study designs, such as adaptive dose-finding designs, designs incorporating plans for sample size recalculation, and futility designs are highly encouraged.

Trials will also be encouraged to include domain-specific or modality-specific endpoints (e.g., that specifically target motor deficits, walking ability, cognitive ability, spatial neglect, etc.) in addition to traditional global endpoints that may foster a more common language across all stroke trials.

Applications for exploratory studies (e.g., early dose finding studies with biomarker outcomes, early proof of mechanism or proof of concept trials) are also encouraged. For medical devices, Early Feasibility and Traditional Feasibility study designs may include single-arm case series, within subject designs, device comparisons, comparisons to historic controls, comparisons to performance controls, or adaptive/Bayesian designs.

Initiation of proposed trials in the network will be based on highly meritorious applications by peer review and high funding priority by the NANDS Council considering also the infrastructure capacity and availability of patient populations considering current ongoing trials within the network.

Applicants may submit a proposed study for any receipt date, but timing of funding and initiation of the study will be determined by the NINDS with input from the NIH StrokeNet leadership as necessary to assure that studies can be conducted within the proposed timeline included in the research plan of the application.

While applications may propose sites outside the NIH StrokeNet network, NINDS expects that any confirmatory (Phase 3) trial conducted within the network will utilize most or all the NIH StrokeNet RCCs. The addition of clinical sites outside the U.S. may be considered for large phase 3 trials when necessary. Information about the country and proposed clinical sites must be included in the application.

Smaller multi-site exploratory trials and biomarker validation studies generally needing more than 4-5 clinical sites for subject accrual are appropriate for the network. In cases where early phase clinical trials that require a limited number of clinical sites to control for variability (i.e., generally fewer than 3-4 sites) may be directed to submit using the NINDS Exploratory Clinical Trials NOFO ( https://grants. nih.

gov/grants/guide/pa-files/PAR-21-236. html ). Potential applicants are highly encouraged to discuss the potential suitability of the proposal with NINDS program staff prior to submission.

The final number of sites needed for a proposed study will be determined following a feasibility assessment by the NIH StrokeNet. Confirmatory (Phase 3) Trials Confirmatory trials are conducted to provide a definitive answer regarding the safety and efficacy of an intervention or to compare the effectiveness of two or more interventions.

The proposed research must address a scientifically important question, provide valuable information to the existing knowledge base, and have public health relevance. The trial design should ensure that high quality, complete data regarding the primary outcome will be collected in the most efficient manner in terms of time, resources, and burden to subjects.

Secondary outcomes should be included only when they are anticipated to provide important supportive or explanatory data. The necessity of each secondary endpoint must be justified in light of cost and patient/researcher burden. Pragmatic trials requiring minimal data collection and low cost per subject are encouraged.

This NOFO also may be used for the submission of an adaptive trial utilizing a seamless Phase 2/3 transition where data from subjects in Phase 2 are included in the analysis of Phase 3.

Examples of appropriate exploratory studies under this NOFO include, but are not limited to, multi-center studies designed for the following purposes: To evaluate and optimize the dose, formulation, safety, tolerability or pharmacokinetics of an intervention in the target population.

To select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., futility trials). To evaluate biological activity relative to clinical endpoints.

To inform the next phase of development of medical devices, usually by finalizing the device design, establishing operator technique, and/or finalizing the choice of study endpoints for the design of a pivotal clinical trial, in addition to providing initial safety data.

Biomarker and Clinical Endpoint Studies Biomarkers, especially neuroimaging markers of vascular pathology, brain ischemia, or recovery after injury, have been developed for stroke research. Applications of biomarkers may include guiding early neuroprotective and reperfusion interventions, monitoring neuroplasticity in stroke recovery, and expediting therapy development.

Some biomarkers have been validated in multi-center studies, but their full potential to advance research awaits standardization and adoption across a clinical trials network. Similarly, for certain stroke trials the roadblock to evaluating a therapeutic approach may be the lack of a validated clinical endpoint.

This NOFO encourages the submission of studies to clinically validate biomarkers or clinical outcomes with demonstrated promise to inform Phase 2 clinical trials. Depending on the scientific questions posed, biomarker studies supported under this program might be stand-alone protocols or could be embedded within a network stroke trial (ancillary study; see below). Studies designed for biomarker discovery are not suitable for this NOFO.

Applicants interested in support for biomarker discovery studies should refer to PAR-22-089 , Development of Biomarkers or Biomarker Signatures for Neurological and Neuromuscular Disorders. NINDS also encourages submission of ancillary studies designed to add scientific aims to active studies being conducted within StrokeNet and that address questions relevant to stroke treatment, prevention, and recovery.

For the purposes of this NOFO, ancillary studies are defined as research activities undertaken to address a scientific question relevant to the parent study and that require access to data or records from the parent study and/or involve collection of additional data, specimens, or records from patients enrolled in the parent study.

Depending on the scientific questions posed, ancillary studies supported under this program might involve the entire cohort participating in the ongoing clinical trial or selected subsets of the participants. In general, all patients in the ancillary study must be participants in the parent trial; however, recruitment of a small number of normal controls may be acceptable provided adequate scientific rationale and reasonable cost.

The research plan should include a justification for why the proposed study requires the use of patients in the parent clinical trial. Ancillary studies must not interfere with the parent study or unduly burden participants. Approved procedures and policies from the parent study must be followed.

Research questions addressed by the ancillary study might include, among others, the study of: Mechanism of action of a disease intervention; Mechanism(s) of disease pathogenesis; Characterization of disease pathology and phenotypes; Development and validation of diagnostic tool and markers; Validation of markers for disease stage, progression, activity, or therapy response; Extension of the scope of participant data collection and assessment to address additional questions related to the primary trial hypotheses (e.g. addition of imaging data at specified time points; addition of clinical or patient-reported outcomes to gain better understanding of impact of intervention).

Applicants should make note of the following: (1) Working with NIH StrokeNet is a cooperative venture between NINDS, the NIH StrokeNet and the applicant. Potential applicants will be provided guidance by NINDS Program Staff and the NIH StrokeNet Executive and Steering Committees. Potential applicants are strongly encouraged to contact NINDS Scientific/Research Contacts (see Section VII.

Agency Contacts) in order to discuss the appropriateness of the proposed study to be conducted within the NIH StrokeNet. Prior to submission of the grant application, applicants will work closely with the NIH StrokeNet in developing their research plan, assessing the feasibility of the study, and developing an appropriate budget to conduct the research.

The additional interaction with the network is intended to harness the scientific clinical trial expertise in the network and to establish early collaborations necessary for successful conduct of the research plan. Potential applicants are strongly encouraged to start the process early and allow ample time (i.e., 6-8 months) to prepare and submit a competitive NIH StrokeNet project application.

(2) Applicants to this NOFO will be required to incorporate the NIH StrokeNet infrastructure into their proposed study, including central coordination through the NCC, data management through the NDMC, and subject recruitment and trial implementation at the RCCs and affiliated sites. It is not required that all sites participate in every trial.

Additional (ad hoc) performance sites that are not currently NIH StrokeNet sites may be proposed to fulfill specific study requirements. All applicants and ad-hoc non-NIH StrokeNet sites will be required to use the clinical trial agreements and central IRB that have been established for NIH StrokeNet.

(3) Following review and prior to the award, the operational clinical protocol for trials selected for funding will be finalized by the NIH StrokeNet protocol working group and are expected to incorporate recommendations that may come from the peer review and NANDS Council process.

The NIH StrokeNet team was established by NINDS based on peer- and Council review to form a group of outstanding clinical trial experts from the fields of neurology, neurosurgery, rehabilitation, and statistics with a proven record of developing high quality protocols. Final protocols will be reviewed and approved by NINDS prior to study initiation. (4) This NOFO is intended to support studies in patients, not healthy volunteers.

Applications to conduct exploratory trials in healthy volunteers should be submitted to a separate clinical trial announcement, https://grants. nih. gov/grants/guide/pa-files/PAR-21-236.

html . All trials proposing to use an investigational agent or device must have an active IND or IDE or documentation of exemption at the time of submission of the application (see NOT-NS-11-018 ).

(5) Device trials: The NIH recognizes that devices can vary greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc. Consequently, the appropriate pathway to market may require a traditional Feasibility study and/or Pivotal study in support of an eventual Pre-Market Approval submission or may require a more limited study to address specific issues in support of an FDA 510(k) or 510(k) De Novo submission.

Clinical studies involving devices may utilize all the centers that are part of the NIH StrokeNet, or a more limited subset of centers selected based on appropriate expertise for the given device. Investigators are encouraged to contact the NINDS Scientific/Research Contact as early as possible to discuss how the NIH StrokeNet may best be utilized in support of their specific device project.

NINDS anticipates that the majority of device projects utilizing NIH StrokeNet will be traditional Feasibility Studies in order to optimally leverage network advantages. An Early Feasibility Study should be designed [in accordance with FDA’s guidance, “Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies”, see https://www. fda.

gov/regulatory-information/search-fda-guidance-documents/investigational-device-exemptions-ides-early-feasibility-medical-device-clinical-studies-including to allow for early clinical evaluation of devices to provide proof of principle and initial clinical safety data while device design and operations are still in development.

A Traditional Feasibility Study is a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan a Pivotal Study.

(6) Rationale: Exploratory and confirmatory clinical trials proposed for this network must anchor their rationale in (i) an unmet medical need; (ii) a plausible biological mechanism; (iii) rigorous preclinical (in vitro and/or in vivo) data; and/or (iv) early clinical data.

The individual weight given to each of these 4 criteria should be carefully assessed in the context of the specific application; there is no requirement to provide support from all four areas.

The major findings of the studies, whether preclinical and/or clinical, that are offered in support of the proposed clinical trial should provide a compelling justification for the phase of study and that the proposed intervention will be effective. Data from preclinical and pilot studies demonstrating the need for and the feasibility of the trial should be presented when available.

Applicants should specifically address the rigor of any animal studies being used as support ( https://grants. nih. gov/grants/guide/notice-files/NOT-NS-11-023.

html ). Preclinical data (such as from animal studies) that do not sufficiently meet the rigor guidelines or are not sufficiently associated with the human condition may be inadequate to support the rationale for the study. (7) Pharmacometrics: Applications seeking to obtain data needed for pharmacometric modeling are permitted, with the ultimate aim of enabling the optimal design of a future efficacy trial of an intervention.

(8) The award and continuation of funding are subject to milestones to be specified in the notice of grant award. (9) NIH Resources: As appropriate, applicants are strongly encouraged to make use of the following resources for clinical research including: Clinical and Translational Science Award (CTSA) program ; NINDS Common Data Elements .

(10) Mobile Technologies: Applicants are strongly encouraged to consider utilizing mobile technologies when appropriate to increase study efficiency, facilitate data collection, and support protocol adherence on the part of research participants and study site staff.

This NOFO will utilize a bi-phasic, milestone-driven cooperative agreement (UG3/UH3) mechanism consisting of a start-up phase of up to one year (UG3) and a full enrollment and execution phase (UH3) of up to 6 years. Applicants must address objectives for both a UG3 and a UH3 phase.

The UG3 phase will support the development of the final protocol, development of case report forms and other resources necessary to the performance of the study; further development of study partnerships; finalization and Institutional Review Board/Data and Safety Monitoring Board approval of the trial protocol, informed consent(s), manual of operations, and clinical trial project management plans.

All necessary regulatory approvals not already provided, including FDA "may proceed" letter if applicable, as well as provision of the necessary drugs, devices or other resources, should be obtained by the end of the UG3 award to allow for the successful launch and execution of the proposed clinical trial, biomarker or ancillary study in the UH3 phase.

In addition, it is expected that enrollment in the study will begin by the end of the UG3 phase or sooner. Subject to NINDS funding availability and scientific priorities, UH3 awards will be made after administrative review with particular attention to the extent to which agreed-upon milestones have been met.

If the UH3 is funded, an additional administrative review will be scheduled during the UH3 phase to assess progress towards UH3 milestones or enrollment milestones. Delineation of milestones is a key characteristic of this NOFO. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity.

Milestones should be reached at the end of the UG3 phase. Milestones must be performance-based to achieve completion of the trial on time and on budget. Satisfactory completion of UG3 milestones will be assessed administratively to determine eligibility to transition to the UH3 implementation phase.

This NOFO will support applications that include a series of annual milestones for completion of the study (UH3 phase) and provide contingency plans to proactively confront potential delays or disturbances in meeting the milestones. NINDS staff in collaboration with the awardee will closely monitor progress at all stages, including milestones, accrual, and safety.

If, at any time, recruitment falls significantly below the projected milestones for recruitment, NINDS may consider an interim no-cost extension or ending support and negotiating a phase-out of the award. Continuation of the award is conditional upon satisfactory progress in meeting milestones and subject to the availability of funds. See Section VIII.

Other Information for award authorities and regulations. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. Section II.

Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for this NOFO. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the requested project award period. The project period for the UG3 phase will be up to 1 year.

The project period for the UH3 phase is expected to be 4 years. With strong justification, up to 6 years for the UH3 may be requested. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply-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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications .

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.

Eligible Individuals (Program Director/Principal Investigator) 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 their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply- Application Guide. The designated study PD(s)/PI(s) is/are not required to be part of the NIH StrokeNet infrastructure in order to be eligible to apply to this NOFO.

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms . 3.

Additional Information on Eligibility 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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 2. 3.

9. 4 Similar, Essentially Identical, or Identical Applications ). 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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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. All page limitations described in the How to Apply- Application Guide and the Table of