and Human Services (HHS)
EXPIRED
Participating Organization(s) |
National Institutes of Health (NIH) |
National Institute of Neurological Disorders and Stroke (NINDS) |
|
Funding Opportunity Title |
NINDS Stroke Trials Network - Regional Coordinating Stroke Centers (U10) |
Activity Code |
U10 Cooperative Clinical Research Cooperative Agreements |
Announcement Type |
New |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
RFA-NS-13-011 |
Companion Funding Opportunity |
RFA-NS-13-012, U01 Research Project Cooperative Agreements |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.853 |
Funding Opportunity Purpose |
The purpose of this funding opportunity announcement (FOA) is to invite applications to participate as a Regional Coordinating Stroke Center in the NINDS Stroke Trials Network. The primary goal of this 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 and Data Management Centers. Additional efficiencies will be encouraged through the use of master trial agreements and a central IRB. Clinical and basic scientists at the centers will contribute to the development of network clinical trial applications for peer review, as well as planning for execution of NINDS-funded stroke clinical trial applications from outside of the network, including trials that result from Collaborative Research and Development Agreements between the NINDS and Industry partners. The Network will also be uniquely poised to rapidly collaborate with other existing networks, such as the NINDS Neurological Emergencies Treatment Trials Network (NETT) or international consortia to conduct larger, definitive trials of promising interventions for the treatment of stroke. 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 Stroke Trials Network will include an active stroke research training program. All network stroke centers will be committed to increasing the value of clinical research data through an aggressive data sharing plan. This FOA solicits applications for Regional Coordinating Stroke Centers for the Stroke Trials Network. Separate FOAs will be issued to solicit applications for the National Clinical Coordinating Center (RFA-NS-13-012) and the National Data Management Center (TBD). |
Posted Date |
February 21, 2013 |
Letter of Intent Due Date(s) |
April 1, 2013 |
Application Due Date(s) |
May 15, 2013 |
AIDS Application Due Date(s) |
Not Applicable |
Scientific Merit Review |
July 2013 |
Advisory Council Review |
August 2013 |
Earliest Start Date |
September 2013 |
Expiration Date |
May 16, 2013 |
Due Dates for E.O. 12372 |
Not Applicable |
Required Application Instructions
It is critical that applicants follow the instructions in the PHS 398 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. While some links are provided, 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.
Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.
Part 1. Overview Information
Part 2. Full Text of Announcement
Section 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) is to invite applications to participate as a Regional Coordinating Stroke Center (RCC) in the NINDS Stroke Trials Network. The network will 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.
The network will provide a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of NINDS-funded stroke trials. It will include multiple RCC's and their affiliated stroke centers with a proven track record of enrolling stroke patients into clinical studies, one National Clinical Coordinating Center (NCC), and one National Data Management Center (DMC). The network 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 comparison between approaches.
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 and 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.
Investigators in the NINDS Stroke Trials Network will forge collaborations to engage in the planning, development and execution of innovative trials designed to best answer the highest priority scientific questions for advancing stroke treatment. The success of the network's phase 1 and 2 activities will be enhanced by strong relationships with preclinical experts in the basic science of cerebrovascular disorders. The investigators will be expected to judge the feasibility of the network’s performance of trials designed outside the network as well as to develop original grant applications for submission to the NINDS peer review.
Biomarkers, especially neuroimaging markers of vascular pathology, brain ischemia, or recovery after injury, have been developed for stroke research. Biomarker-validation studies that are immediately preparatory to trials will also be considered by the Stroke Network. The potential applications of biomarkers are to guide early neuroprotective and reperfusion interventions, to monitor neuroplasticity in stroke recovery, and to expedite therapy development. Some biomarkers have been validated in multi-center studies, but their full potential to impact research awaits standardization and adoption across a clinical trials network.
Clinical trials require a network of experienced clinical research, data management, clinical trial personnel, as well as infrastructure for data capture and storage, and the recruitment and retention of participating patients. Clinical trials are time consuming and expensive, often requiring as much as 10 years or more to complete. These constraints can drain the resources of funding agencies, investigators, industry, clinical resources, and patients and may discourage innovative strategies and collaborations with industry and international stroke trial consortia intent on achieving common goals.
In the traditional model, a consortium of clinical sites is created for each new multi-center trial. This leads to redundancy because infrastructure resources are duplicated. Also, time is lost when common start-up activities are repeated for each trial. Multiple, uncoordinated contract negotiations and Institutional Review Board (IRB) approvals often cause further delays and create challenges for industry partnerships. This is especially critical given industry's perception that new stroke therapies are too difficult and risky to pursue. Therefore, highly meritorious, peer reviewed clinical trials developed under Collaborative Research and Development Agreements (CRADA) between NINDS and industry partners may also be performed by the network.
Another limitation of the traditional research model is that it is difficult to access and combine data across trials to enable meta-analysis and the development of new research questions. A major opportunity for the network is to coordinate and integrate data across the spectrum of NINDS funded stroke trial research. This and the use of Stroke Common Data elements (CDE's) will ensure synchronized and uniform collection of clinical, neuroimaging and biological data, and it will potentially lead to innovative new methods such as the integration of patient reported outcomes or electronic health record data in large, "pragmatic", clinical trials. Comparison of results across studies and for metadata analysis would increase the value of collected data, and thus the contribution of study participants.
Lastly, without an ongoing trial network, there may be loss of expertise and real-world clinical knowledge as stand-alone trials finish. The lack of consistent activity at a site may lead experienced research coordinators to move to other fields after a trial is completed. The NINDS Stroke Trials Network will enable the integration of lessons learned from previous or ongoing trials to ensure successful, impactful clinical research. Involvement in most NINDS-funded stroke trials will allow the development of an experienced clinical stroke trial workforce and enhance stroke research.
Stroke care requires contributions from a variety of health professionals across multiple disciplines. Lack of integration of these multiple components into an effective stroke research infrastructure limits the ability of NIH-funded research to advance the care of stroke victims. The stroke trials network will be expected to integrate the various stroke-related disciplines and develop and execute interdisciplinary research applications that answer questions with high public health impact. The interdisciplinary nature of the NINDS Stroke Trials Network will also serve to build research capabilities that match the scientific opportunities across the spectrum of stroke research.
The network aims to harness multidisciplinary stroke expertise to collaboratively and efficiently conduct exploratory NINDS-sponsored phase 1 and 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 the NETT or international consortia will facilitate the execution of the larger, phase 3 definitive trials. Together with the larger U.S. and 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 and Data Management Centers to ensure that all eligible stroke patients are considered for NINDS-funded trials.
Once the network has been established, the NINDS expects that it will be the primary and first-line infrastructure involved in implementing all multi-site stroke trials submitted to the NINDS.
The NINDS Stroke Trials Network will include: one NCC, one DMC and up to 25 RCC's that have the capacity of coordinating activities in a large number of Stroke Centers across the United States. This FOA solicits applications for funding of infrastructure for RCC's in the NINDS Stroke Trials Network. The additional project-specific funds to support the implementation of protocols conducted in the network will be from separate awards. Projects may 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, according to protocol budgets approved by the network Steering Committee (SC) and via master trial agreements with the RCC's.
In addition, for large, simple, acute stroke trials the NINDS Stroke Trials Network may collaborate with the NINDS Neurological Emergencies Treatment Trial (NETT) network to coordinate trial activities. RCC's in the network should be able to conduct trials in adult populations, pediatric populations, or both, and it should have a rapid stroke system to treat and enroll patients within the first couple hours of a stroke. Investigators at the NIH Clinical Center may also function as an additional clinical site.
Expectations of the Stroke Research Centers
The RCC 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 will include stroke specialists from neurology, pediatric neurology, emergency medicine, neurosurgery, neuroimaging, interventional radiology, neurointensive care, neurorehabilitation, and other medicine specialists and emergency medical services. RCCs will 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 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.
It is advantageous if the RCC's in the NINDS Stroke Trials Network consider working with a central IRB which will be implemented by the NCC. The central IRB's function would be similar to the NeuroNEXT (NINDS Network for Excellence in Neuroscience Clinical Trials) model although the actual templates to be used in the stroke network may be different from the ones used in NeuroNEXT (see as an example NeuroNEXT.org for the IRB reliance agreements and master trial agreements used in NeuroNEXT).
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 Stroke Network.
National Clinical Coordinating Center
The NCC will provide overall study coordination, working closely with the DMC and the RCC's. The NCC will coordinate the activities of the SC, 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 to be submitted to the NINDS for peer review for future execution in the Stroke Trials Network. In addition, the network coordinating center will collaborate with the DMC in developing and implementing data management procedures. Both centers will be responsible for quarterly progress reports to the NINDS and one or more DSMBs. See RFA-NS-13-012 for more details describing the responsibilities of the stroke network NCC.
National Data Management Center
The DMC will support protocol data management, ensure data quality control (including data monitoring), and undertake interim monitoring, analyses and reporting for the NCC, NINDS, and Data and Safety Monitoring Boards (DSMBs). The DMC will also initiate and coordinate activities to promote standardization of data elements using the NINDS Stroke Common Data Elements and support an aggressive sharing policy for de-identified data. The funding announcement describing the responsibilities of the stroke network DMC will be released subsequent to this FOA.
The NINDS will be responsible for organizing and providing overall support for the network. The NINDS Office of Clinical Research staff and the NINDS Office of 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 a NINDS partner, consistent with the Cooperative Agreement mechanism. The NINDS will appoint the Data and Safety Monitoring Board (DSMB) and the Scientific Advisory Board (SAB). The SAB is an external group of experts who will review the network program and provide individual feedback to the network investigators and the NINDS.
Network Committees
1. An Operations Committee for the network will consist of the Program Director/Principal Investigator (PD/PI) of the NCC (who will serve as the chair), a co-PD/PI, if designated, the PD/PI of the DMC, the NINDS Project Scientist, 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 activities and monitor performance. It is anticipated the Operations Committee will meet by telephone conference calls on a weekly basis.
2. A Steering Committee (SC) will consist 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.
3. Data and Safety Monitoring Boards (DSMBs) will be established by the NINDS in accordance with NIH policies and with input from the SC, will monitor patient safety, and review study performance.
Network Projects
Over the next 5-year project period, the network will initiate approximately 4-5 NINDS-funded exploratory phase 1 and 2 stroke clinical trials and 2-4 phase 3 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. The network may also be used to conduct NINDS-funded projects that were initiated before the network was established. Informed by the results of ongoing research and the stroke planning effort it is anticipated that a number of projects will be solicited by NINDS to be performed in the network. Projects may also be submitted using the standard NINDS clinical trial funding announcements (e.g., PAR-10-199: NINDS Exploratory Clinical Trials (R01) or PAR-11-173: NINDS PHASE III Investigator-Initiated Multi-Site Clinical Trials (U01)). Future funding announcements by the NINDS for the solicitation for network trials may also be developed.
Funding Instrument |
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities. |
Application Types Allowed |
New The OER Glossary and the PHS 398 Application Guide provide details on these application types. |
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. NIH intends to fund an estimate of up to 25 awards, corresponding to a total of $8,750,000 for fiscal year 2013. Future year amounts will depend on annual appropriations. |
Award Budget |
The maximum allowable direct cost per year for a NINDS Stroke Network clinical (hub) site will be $250,000. |
Award Project Period |
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
For-Profit Organizations
Governments
Other
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 the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.
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 PHS 398 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.
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 investigators, 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; however, it is preferable that only one principle investigator be identified for the RCC application.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.
It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
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, Ph.D.
Program Director
Neuroscience Center, Room 2191, MSC 9520
6001 Executive Boulevard
Rockville, MD 20852 (courier)
Bethesda, MD 20892-9520
Phone: 301-496-9135
Fax: 301-480-1080
Email: [email protected]
Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Boulevard
Bethesda, MD 20892-9529 (Rockville, MD 20852 for express/courier service)
Phone: 301-496-9223
Fax: 301-402-0182
Email: [email protected]
All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, with the following additional requirements.
While the Research Strategy is limited to 12 pages, it should be divided into the following sections with the designated page limits.
A. Program Overview - 3 pages
B. Research Program - 3 pages
C. Leadership - 2 pages
D. Training Program - 2 pages
E. Administration - 2 pages
All instructions in the PHS398 Application Guide must be followed.
All instructions in the PHS398 Application Guide must be followed, with the followin additional instructions:
Senior/Key Personnel and Other Significant Contributors:
Table of Contents
All instructions in the PHS 398 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.
Biographical Sketch
All instructions in the PHS 398 Application Guide must be followed.
The availability of facilities, including neuroimaging, neurointerventional, neurosurgical capabilities, laboratories, inpatient and outpatient resources, EMS units, rehab, etc., must be described. Applicants should discuss their capability to participate in a distributed data entry system, since clinical centers should be able to interact with the DMC to transmit and edit data. The applicant should describe how local clinical research resources such as equipment, space and research staff will relate to the network.
It is advantageous that RCC consider working with a central IRB and master contract agreement implemented by the NCC. Institutions should therefore state their willingness to commit to the use of a master trial agreement and a central IRB coordinated by the network NCC.
Institutions will be required to document commitment to the PD/PI by providing departmental and institutional support letters, and they are encouraged to demonstrate support via other means (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI and/or network center). For those centers at institutions with a Clinical Translational Science Award (CTSA) the applicants are encouraged to include documentation from the CTSA PD/PI regarding how the clinical and translational stroke research can be strengthened by the infrastructure funded through the CTSA, and what specific support is provided.
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Research Strategy: The Research Strategy must consist of the following Sections A E.
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 in the group’s practice setting(s) and provide a summary of the group’s accrual to these trials.
B. Research Program
The application should describe the group’s plans and approach to implementing stroke clinical 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 expertise or unique strengths 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, applicants should include a brief paragraph to describe if and how they could contribute (i.e., design, leadership, expertise, etc.) to potential future trials of: a) an adaptive trial to identify which of the currently available intravenous thrombolytic drugs, either alone or in combination with other strategies, are superior for the treatment of acute ischemic stroke within the current time window; b) a trial to determine whether ischemic stroke patients with evidence of tissue at risk on acute CT or MR imaging will benefit from intravenous or endovascular reperfusion therapy in an extended time window; and c) a stroke recovery study of a critical biomarker or an impairment-focused treatment during the initial 3 months after stroke. Applicants 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.
C. Leadership
A designated PD/PI is required. A substitute PD/PI candidate should be identified to assure continuity in the event of resignation of the PD/PI. The qualifications and experience of both persons must be described, specifically documenting their respective abilities to organize and manage a RCC in the network, as well as experience in accruing patients/participants to clinical trials. In addition, 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.
In addition, the application should describe the leadership positions held by the PD/PI with the RCC’s affiliated research bases as well as contributions made in that position along with their impact. Parallel descriptions should be given for other Senior/Key personnel, if applicable.
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
The network presents a rich environment for young investigators to be exposed to and develop additional research skills, and it can assist them in progressing to more senior status. To support this, each application must include a fellowship training and career development program (with a minimum required allocated budget of $50,000 in direct costs per year). The RCC must demonstrate a consistent and significant commitment to a training program in stroke research. The NINDS is committed to the career development of clinically trained research scientists. The Institute supports several programs to advance the careers of clinician-scientists by: (1) encouraging the interest of outstanding physicians early in their career; (2) accelerating entry to independent research; (3) encouraging translational research; and (4) fostering research training by especially competent laboratories. The RCC will select candidates for career development who demonstrate potential for independent research careers or who are established investigators and are changing the direction of their research careers. In its selection process the RCC will seek out and include qualified minorities, women, and persons with disabilities for inclusion in the career development program. After an individual is selected, a specific plan will be developed and facilitated by the leadership of the site. A budget will be proposed for sustaining a significant activity in career development for a maximum of one year while applications for any further support are prepared. Further support would have to come from career development grants from NIH or other organizations. For example, the NINDS sponsors career development awards, minority career development supplements, and fellowships. 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 identify the training Director and names of faculty members who will serve as mentors (with a brief description of their research) at their center with their 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 the candidates will be selected and how applications will be solicited (i.e., only at one institution or include neighboring institutions), and who will be on the selection committee.)
E. Administration
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
A statement of commitment from each participating institution or organization must be provided. In addition, an institutional letter of support from the applicant's departmental and/or institutional leadership must be included in the Letters of Support section of the application. It should address how the institutional commitment will be established and sustained, how the institution will maintain accountability for promoting scientific excellence, and how the stroke network site research effort will be given a high priority within the institution (relative to other research efforts and non-NIH supported programs.) The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the network site director, assignment of specialized research space, cost sharing of resources, and/or other ways proposed by the applicant institution. Letters from a high-level institution official(s) (e.g., Dean of the School of Medicine, Hospital President, and Vice President for Research) should be included confirming this commitment.
There must be clear evidence in the application of a strong commitment from the stroke service, rehabilitation service, emergency medicine, interventionalists and neurosurgeons and the institution of their willingness to participate in NINDS clinical stroke trial protocols and to consider randomization of all eligible subjects to answer important scientific questions with major public health impact.
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide.
Appendix
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.
Part I. Overview Information contains information about Key Dates.
Information on the process of receipt and determining if
your application is considered on-time is described in detail in the PHS 398
Application Guide.
Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.
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 received on or before the due dates in Part I. Overview Information. If an
application is received after that date, it will not be reviewed.
Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by NINDS.
Applications that are incomplete and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
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 proposed RCC 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 RCC 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 RCC that by its nature is not innovative may be essential to advance a field.
Significance
Does the RCC address an important problem or a critical barrier to progress in the field? If the aims of the RCC 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? How will the proposed RCC contribute to the advancement of clinical research and clinical trials within the framework of the network?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the RCC? 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?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Approach
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the RCC? 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?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion 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? Is the description of the RCC's consideration of the potential future trials indicative 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?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
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 consider the use of a central IRB and master trial agreement coordinated by the NCC?
As applicable for the RCC 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.
A. Program Overview
Background and Experience. How adequate is the experience of the applicants 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?
Catchment Area. 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?
Organizational Structure. How appropriate is the planned organizational structure to accomplishing the proposed research activities?
Institutional Commitment. Does the structure appear realistic and is there adequate institutional commitment? How convincing are the supporting documents from participating institutions? Are the available facilities, including laboratories, in-patient and outpatient resources, and space for administrative activities adequate to support the proposed research activities?
Relevant Accomplishments. How relevant are the group’s accomplishments in implementing clinical trials in stroke in the group’s practice setting(s) to the goals and requirements for the network?
B. Research Program
Research Plans. 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?
C. Leadership
Key/Senior Personnel. Are the qualifications, training, and experience of the PD/PI appropriate for organizing and managing a research program that includes accrual to network-approved trials as well as design and development of clinical trial protocols and research applications?
Has the PD/PI demonstrated effective leadership abilities in the community served by the center and/or to the affiliated sites? Have other Key/Senior personnel taken on leadership roles that contribute to the success of the site and/or the research agenda of the affiliated spokes?
D. Training Program
Does the proposed plan for the career developmental plan describe how promising candidates for independent careers (academic, industrial, governmental) in translational stroke research will be selected?
Does the proposed plan address how the investigators will seek out and include qualified women and minorities for participation in the proposed program?
E. Administrative Management
Operations. Are the management structures, standard operating procedures, and workflow processes for conducting clinical trials clear and adequate for the proposed program goals? Are the personnel and their duties appropriately matched?
Protections for Human Subjects
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 Human
Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the RCC proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Not Applicable.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, bio-containment, and security of the Select Agent(s).
Resource Sharing Plans
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) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center and 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.
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 the DUNS, SAM
Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants 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.
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the 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:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel 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.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, 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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]
eRA Commons Help Desk (Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]
Dr. Scott Janis
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]
Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]
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 Parts 74 and 92.
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