National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
NIH StrokeNet Regional Coordinating Stroke Centers (U24)
U24 Resource-Related Research Projects – Cooperative Agreements
The purpose of this funding opportunity announcement (FOA), issued by NINDS, is to invite currently awarded NIH StrokeNet centers and potential new stroke centers to participate as a Regional Coordinating Stroke Center in the NIH StrokeNet clinical trials network. The goal of this existing network is to maximize efficiencies to develop, promote and conduct high-quality, multi-site clinical trials focused on key interventions in stroke prevention, treatment, and recovery with the objective to have a balanced portfolio between all three approaches. Exploratory Phase 1/2 and confirmatory Phase 3 clinical trials as well as biomarker-validation studies that are immediately preparatory to trials will be coordinated through separate National Clinical Coordinating (NCC) and National Data Management Centers (NDMC).
Funded regional coordinating stroke centers 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. Each regional stroke center will also have strong collaborative relationships between vascular neurology, emergency medicine, interventional neuroradiology, neurosurgery, neurointensive care, neuroimaging, stroke rehabilitation, and pediatric neurology, indicating a commitment to offer every eligible patient the opportunity to participate in a trial conducted through the network. In addition, the NIH Stroke Trials Network will include an active stroke research career enhancement program. All network stroke centers will be committed to increasing the value of clinical research data through an aggressive data sharing plan.
May 10, 2017
August 25, 2017
30 days prior to application due Date
September 25, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
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.
September 26, 2017
It is critical that applicants follow 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 the 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.
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.
I. 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
The purpose of this funding opportunity announcement (FOA), issued by NINDS, is to invite currently awarded NIH StrokeNet centers and potential new stroke centers to participate as a Regional Coordinating Stroke Center (RCC) in the NIH StrokeNet Stroke Trials Network. The goal of this existing network is to develop and conduct high-quality, multi-site Phase 1/2 and Phase 3 clinical trials focused on key interventions in 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.
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, but in North America stroke has fallen to the fourth most common cause of mortality as the result of ongoing successes in prevention and acute care. 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 with multiple possible underlying causes. Although stroke impacts all age groups (including children and especially neonates), the incidence is strongly linked to aging. Stroke will become increasingly prominent in the next 30 years with the projected rise in the proportion of elderly in the US, and it 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.
The Stroke Progress Review Group and NINDS stroke planning efforts identified a need for stroke trial network infrastructure to effectively pursue a number of scientific opportunities and to accelerate translation (see http://www.ninds.nih.gov/find_people/ninds/OSPP/Stroke-Research-Priorities-Meeting-2012.htm). The unbiased evaluation of newly-developed and existing interventions-drugs, devices and systems of care-in randomized, controlled clinical trials are necessary to establish efficacy of interventions for improving important clinical outcomes. Phase 1/2 trials explore safety, target engagement, proof of biological concept, and dose response to inform Phase 3 efficacy trials. Phase 3 efficacy trials are designed to demonstrate clinical benefit that patients consider meaningful. Comparative effectiveness trials examine how to best apply established efficacious treatments.
In 2013, the NIH StrokeNet was established to conduct clinical trials in a centrally coordinated network that includes 25 regional centers that are linked to over 350 stroke hospitals across the United States. The NIH StrokeNet was designed to rapidly initiate and efficiently implement small and large multi-site exploratory and confirmatory clinical trials focused on promising interventions for stroke prevention, treatment and recovery, as well as validation studies of biomarkers or outcome measures. The network includes an education platform designed to train the next generation of stroke clinical researchers and collaborations from a variety of health professionals across multiple disciplines. The interdisciplinary nature of the NIH StrokeNet is expected 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.
The aims of the network are to harness multidisciplinary stroke expertise to collaboratively and efficiently conduct exploratory NINDS-sponsored Phase 1/2 clinical trials for stroke interventions with the goal to quickly move potential treatments into larger, confirmatory Phase 3 trials. In addition, the network may perform biomarker validation studies that are immediately preparatory to clinical trial(s). Collaboration with international consortia will facilitate the execution of the larger, Phase 3 definitive trials. Together with the larger U.S. and the international stroke research community, stroke patients, and stroke-related nonprofit associations, the investigators at the RCC's will work to design and execute the most clinically impactful stroke research.
Study execution and performance will be monitored by the NINDS and the National Clinical Coordinating (NCC) and National Data Management (NDMC) Centers 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.
The NIH StrokeNet currently includes: one NCC, one NDMC and 25 RCC's that have the capacity of coordinating activities in a large number of Stroke Centers across the United States. This FOA encourages both currently awarded network centers and new center applications for funding of infrastructure for RCC's in the NIH StrokeNet. The additional project-specific funds to support the implementation of protocols conducted in the network will be from separate awards. Projects can come from academic investigators, from small business or industry through a CRADA or from the NINDS through a specific funding opportunity announcement. Collaborative projects developed by site investigators in the network will be strongly encouraged. These funds will be distributed to the RCC's via the NCC on a per-patient basis protocol budgets via master trial agreements with the RCC's.
Expectations of the Stroke Research Centers
To be selected as an RCC in the NIH StrokeNet, the center must demonstrate both clinical science excellence and specialized expertise in stroke management, a strong background in stroke research, and a proven ability to recruit stroke patients that include 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, and other medicine 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. 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 adequate patient enrollment.
All RCC's in the NIH StrokeNet are expected to be committed to working with a central IRB which is maintained by the NCC. Additionally they will be expected to agree to a master trial agreement with the NCC to distribute all trial-related payments. Additional information on the current agreements can be found at: www.nihstrokenet.org/documents.
RCCs may choose to include geographically or organizationally linked partners or satellite stroke centers, such as other academic centers and/or private and community hospitals and clinics. Such satellite centers could be venues for additional patient enrollment or might provide access to patient populations not traditionally cared for at the RCC. The RCC will be responsible for providing scientific leadership and regular communication to satellite centers regarding protocols and study progress and for providing administrative and budget support for protocol initiation. In addition, preclinical stroke activities at the RCC's will contribute to the development of compelling clinical research applications and also enhance training opportunities. A typical RCC in the network is envisioned as a regional academic medical center or tertiary care facility capable of providing research support for its collaborative stroke centers. The NCC will manage ongoing operational issues, such as subcontracts for capitated payments, protocol-specific site training, and site monitoring. The productivity of the partners and satellites will be considered part of the RCC’s contribution to the NIH StrokeNet.
National Clinical Coordinating Center
The NIH StrokeNet NCC provides overall study coordination and works closely with the NDMC and the RCC's. 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 RCC's and distribute funding for network trial projects, maintain regulatory documents and coordinate the central IRB process, monitor eligibility of participants, assure compliance with regulations and monitor the informed consent process, prepare blinded reports on adverse events, monitor study execution at sites, support outreach to patients and inclusion of patients in protocol and recruitment plan development, supervise and encourage recruitment, coordinate editorial and manuscript preparation, and develop operational and publication guidelines within the framework outlined by the network NCC FOA. The NCC will also coordinate the development of clinical trial protocols as well as the clinical budgets to be submitted to the NINDS for peer review for future execution in the NIH StrokeNet. In addition, the NCC will collaborate with the NDMC in developing and implementing data management procedures.
National Data Management Center
The NDMC supports protocol data management, ensures data quality control (including data monitoring), and undertakes interim monitoring, analyses and reporting for the NCC, NINDS, and Data and Safety Monitoring Boards (DSMBs). The NDMC also initiates and coordinates activities to promote standardization of data elements using the NINDS Stroke Common Data Elements and support an aggressive sharing policy for de-identified data.
National Institute of Neurological Disorders and Stroke
The NINDS will be responsible for organizing and providing overall support for the network. The NINDS Division of Clinical Research staff 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 awardees as an NINDS partner, consistent with the Cooperative Agreement mechanism. The NINDS maintains the 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 provide feedback to the network investigators and the NINDS on a bi-annual basis.
1. An 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, and selected PD/PI's or their designees from the RCC's. The Executive Committee will provide strategic network leadership and overall network management. It is anticipated the Executive Committee will meet by telephone conference calls on a bi-monthly basis.
2. A Steering Committee (SC) consists of the PD/PI of the NCC and DMC, the NINDS Project Scientist, and the PD/PI or their designees from each of the network RCC's. The Steering Committee will be the main governing body of 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 telephone conference call (potentially more frequently during the start-up phase of the network) and 1-2 times per year by in-person meetings. Awardees will be required to accept and implement policies approved by the SC.
3. An Operations Committee for the network consists of the Program Director/Principal Investigator (PD/PI) of the NCC (who will serve as the chair), the PD/PI of the DMC, the NINDS Program Official and selected PD/PI's or their designees from the RCC's. The Operations Committee will oversee all the network's operational activities (including MTA's, RA's, and other agreements) and monitor trial performance. It is anticipated the Operations Committee will meet by telephone conference calls on a weekly basis.
4. Working Groups for stroke prevention, treatment and recovery; imaging and training Cores, and advisory committees for ethics and competing trials, minority recruitment and retention, interventional management, and pediatric stroke comprised of members from the coordinating centers and each of the RCC's perform a variety of functions, such as but not limited to:
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.
Over the next 5-year project period, the NINDS expects the network will conduct approximately 5-10 NINDS-funded exploratory and Phase 3 confirmatory trials (http://nihstrokenet.org/clinical-trials/trials). The exact number of protocols supported will depend on 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 the network, from investigators outside of the network, or from a CRADA between the NINDS and an Industry partner. Projects may be submitted using the NIH StrokeNet funding announcements (e.g., PAR-14-220: Clinical Trials and Biomarker Studies for Stroke Treatment, Recovery, and Prevention (U01); PAR-14-252: Small Business Innovation Research (SBIR) Cooperative Agreement Awards (U44); and PAR-14-253: Resource Access Award (X01).
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support 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 FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NIH intends to fund an up to 25 awards, corresponding to a total of $8,700,000, for fiscal year 2018. Future year amounts will depend on annual appropriations.
The Maximum allowable direct cost per year for a NIH StrokeNet RCC will be $200,000
The project period is limited to 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
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 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.
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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Only one RCC application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Awards for a NCC and a RCC may be made to the same institution. However, it is preferable that the NCC and the RCC grant at a given institution be awarded to two PDs/PIs, to ensure that the NCC activities as well as the local RCC activities receive full attention.
A RCC may be from a single institution or may include geographically or organizationally linked partners or satellite sites, such as other academic centers and/or private and community hospitals and clinics as needed to fulfill the research requirements.
Buttons to access the online ASSIST system or to download application forms 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.
It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
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:
The letter of intent should be sent to:
Scott Janis, PhD
Neuroscience Center, Room 2191, MSC 9520
6001 Executive Boulevard
Rockville, MD 20182 (courier)
Bethesda, MD 20892-9520
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following suggested organization:
While the Research Strategy is limited to 12 pages, it should be divided into the following sections.
A. Program Overview
B. Research Program
D. Training Program
E. Administrative Core
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed. A statement of commitment from each participating institution or organization and/or documentation of consortium arrangements must be provided
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:
All instructions in the SF424 (R&R) Application Guide must be followed.
Budget requests may include the following allowable items:
The following items are NOT allowed in the budget requests:
The release of funds will be milestone-driven, according to milestones to be specified in the Notice of Award. RCC's that do not meet the milestones may be terminated, if necessary.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
The Research Strategy must consist of the following Sections A-E.
NOTE: An application from a currently funded NIH StrokeNet RCC (i.e., renewing application) must include a progress report under sub-section A –Program Overview.
A. Program Overview
Background and Experience. Describe the group’s history and experience in conducting NINDS-sponsored stroke clinical research, in particular, cooperative group trials. The application should provide details of experience working together as a group, particularly in implementing clinical trials in stroke and related activities.
Catchment Area. The application must delineate its catchment area. Include a description or map of the service area, designating counties or zip codes from which approximately 80 percent of the patients will be drawn. Particular attention should be given to underserved populations in proximity of the institution. A description of the study population in the application’s catchment area, with a breakdown by percentage of the gender and minority composition, should be provided.
Organizational Structure. The application must describe the current and/or planned organizational structure under which it proposes to operate. If the RCC has more than one component/affiliate institution, describe the relationship of component(s)/affiliate(s) to each other and to the RCC. Include the distance between these institutions (including administrative office and shared resources) and location of proposed personnel.
Relevant Accomplishments. Describe the group’s accomplishments relative to implementing stroke clinical trials according the appropriate situation below:
B. Research Program
The application should describe the group’s plans and approach to implementing and conducting NIH StrokeNet clinical trials (NIH StrokeNet trials) in the practice setting(s) of the community it serves. The plans should cover the next 5 years. The plans should include a description of how the RCC will access an adequate selection of eligible patients to meet or exceed accrual requirements and/or planned accrual goals.
Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with other RCC's, the NCC and DMC, and the NINDS and its partners in all aspects of the network program. Applicants are encouraged to describe any special team expertise or unique strengths of the team as a whole they can offer to the collaborative effort (e.g., team leadership and training, protocol adherence strategies, dissemination activities, recruitment strategies).
Applicants should describe the potential pool of co-investigators at the site and their area of expertise. The applicant should indicate how co-investigators will be identified, motivated, and integrated into the network, and how the network team will support the co-investigators. A detailed plan must be included on outreach and collaboration with other clinical investigators at the RCC, because the success of the network will depend on collaboration with co-investigators with protocol-specific clinical research expertise.
Applicants should indicate their willingness to work within the network to propose timely clinical trials. Investigators awarded an RCC grant to the network will be requested to provide a record of their contributions on each annual progress report and continuation of support may rely partially on its collaboration to bring meritorious trials into the Network.
To demonstrate their capabilities or potential future contributions to the NIH StrokeNet, applicants should include a brief paragraph to describe how they could contribute (i.e., development, design, leadership, expertise, etc.) to potential future trials in stroke prevention, treatment and recovery. Applicants should specifically address involvement and potential contributions from preclinical stroke laboratories and researchers at their institutions. Additionally, they should also comment on their capacity for pediatric studies.
Applicants should indicate their willingness to attend all network investigator meetings, which will include conference calls at least 1-2 times a month and in-person meetings at least 1-2 times a year.
The application should include a plan for how the PD/PI will monitor performance and collect data on startup, recruitment and retention for new and potentially also for ongoing NINDS-funded clinical trials at the RCC and any applicable satellite sites.
The application should describe the strategy used by the PD/PI and Institutional official to delegate leadership responsibility with respect to the trials selected for activation by the network and how the responsibility is delegated among key/senior individuals.
As the leader of the RCC, it is expected that the PD/PI plays a leadership role in some capacity to the community served by the group. The application should describe the leadership role played by PD/PI and other Senior/Key personnel (if applicable) and the impact it would have on the success of their center as well as on the overall stroke trials network.
A mentoring plan or program for leadership succession within the site is recommended to ensure a smooth transition of leadership if and when necessary. If such a plan exists or is under development it should be described in the application.
The application should propose a committed group of multidisciplinary professionals appropriate for its expected clinical trials participation. This team should include experts from emergency medicine, neurology, neurointensive care, physiatry, neuroradiology, neurosurgery, interventional neuroradiology, pediatric neurology and subspecialists, varying depending on local circumstances, as appropriate. The success of the overall network will be enhanced by advice and input from preclinical basic and translational stroke investigators. Collaborators at the network site with special expertise in stroke biology who might contribute to the development of phase 1 and 2 clinical trial grants should also be identified. A description of the RCC team, how they operate and interact and how they lend their special expertise to achieve the goals of the RCC, as well as to the success of the overall network, should be provided.
D. Training Program Career Enhancement Program
The network presents a rich environment for early stage investigators to be exposed to and develop additional research and clinical trial skills that are critical for pursuing careers in academic clinical research. To support this, each application must include a program that will provide research experiences and career enhancement opportunities to early stage investigators. The RCC is expected to support at least one early-stage investigator annually, and should plan on allocating a minimum of $50,000 in direct costs per year toward salary support for each candidate selected. The RCC must demonstrate a consistent and significant commitment to career enhancement to early stage investigators in stroke research. The RCC will be encouraged to select candidates who demonstrate potential for independent research careers and to seek out and include qualified minorities, women, and persons with disabilities. After an individual is selected, a career enhancement plan will be developed through collaboration with the network and facilitated by the leadership of the RCC. Selected early-stage investigators will be encouraged to pursue other NINDS-sponsored career development awards and fellowships following their NIH StrokeNet career enhancement experience. For a description of these programs, please consult the NINDS training and career development website: http://www.ninds.nih.gov/funding/areas/training_and_career_development/index.htm.
Applicants should their center's experience in mentoring clinical fellows in stroke. Applicants should describe their eligible resident pool (e.g., number of stroke, emergency, interventional, etc. residents) and their site's history of training fellows in stroke clinical research. Applicants should briefly describe how applications will be solicited (i.e., only at one institution or include neighboring institutions), who will be on the selection committee, and how the candidates will be selected.
E. Administrative Core
Operations: The application should describe the RCC's standard operating procedures and how the workflow is implemented for activating trials, accruing and following participants/patients, and collecting and managing the data associated with the trials and trial accrual. Describe the hierarchy the center has in place to oversee the day to day operations for conducting clinical trials. In addition, describe the plans for communication among physicians and component/affiliate institutions and incentives for participation in clinical trial accrual. The qualifications, experience, and proposed duties of all proposed support personnel should be described.
Data Management & Quality Assurance: The internal quality assurance plan and procedures of the RCC should be described. Assurance of quality is the joint responsibility of the center and its affiliated satellite stroke centers. Procedures for data collection and investigational drug monitoring must be described in the application. For data management procedures, include details on the following: who is responsible for data management overall; what is the source of records (e.g., hospital, office, clinic, registry); who will register patients on trials; how will the information flow; who will enter data on primary patient records and study forms (e.g., nurses, physicians, data managers, secretaries); who will collect and send patient materials (e.g., pathology slides, port films, etc.) to the centers if required; and what systems are in place for electronic data transfer.
Letters of Support:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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 DUNS number it provides on the application is the same number 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. Applications that are incomplete and/or non-compliant will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
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).
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.
Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?
Does the PD/PI have a track record of working collaboratively? Is there evidence of a strong relationship between neurology, emergency medicine, interventional neuroradiology/neurosurgery and neurorehabilitation? Does the PD/PI have a track record in successfully implementing stroke clinical trials? Is there evidence of experience in and willingness of the various stroke-related services and preclinical stroke laboratories to participate appropriately in a collaborative program as described in this FOA? How adequate is the experience of the applicant's team in conducting stroke clinical trials and working together as a group in implementing clinical trials? Is the overall team of professionals participating in the site group appropriate and adequate to achieve the goals and aim of the program?
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?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?
Are interactions/communications between investigators at the RCC clearly described and creatively optimized? Do descriptions of the RCC's future roles in potential clinical trials indicate that the site is likely to be a productive contributor to the overall network? Does the RCC demonstrate a willingness to do a range of stroke trials? Is the patient population large enough and do the physicians affiliated with the proposed site group see enough of patients to ensure that the site will be able to meet or exceed the accrual requirements in the network-approved clinical trials? Are the site’s plans for implementing network-approved clinical trials well thought out and appropriate for the group’s structure and capacity? Does the application provide evidence that they will establish standardized master trial agreements with the NCC? Are the recruitment/retention plans and outreach plans adequately described and a rationale provided for the likely effectiveness of the plan? How effective is the existing site group (or new group applicants) in engaging the community served? Are the affiliations of the RCC with their satellite stroke centers appropriate and consistent with the rationale provided in the application? Does the proposed plan for career enhancement describe how promising candidates for independent careers (academic, industrial, governmental) in stroke research will be selected?
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?
Is there adequate evidence of institutional and departmental commitment to the PD/PI (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI)? Does the application indicate the willingness of the Institution to use of a central IRB and master trial agreement coordinated by the NCC?
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.
For research that involves human subjects but does not involve one of the six 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 six 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.
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 children 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.
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.
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.
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.
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).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
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.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council. The following will be considered in making funding decisions:
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.
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 grantee’s business official.
Awardees 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.
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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
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 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75and 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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
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.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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.
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
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
(Questions regarding application instructions and process, finding NIH grant
Email: GrantsInfo@nih.gov (preferred method of contact)
Scott Janis, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Tijuanna DeCoster, Ph.D., MPA
National Institute of Neurological Disorders and Stroke (NINDS)
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.
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