Department of Health and Human Services


Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title

NINDS Stroke Trials Network - National Data Management Center (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number

RFA-NS-13-016

Companion Funding Opportunity

RFA-NS-13-011, U10 Cooperative Clinical Research – Cooperative Agreements
RFA-NS-13-012, U01 Cooperative Clinical Research – Cooperative Agreements 

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.583 

Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to invite applications to participate as a National Data Management Center for the NINDS Stroke Trials Network.  Separate FOAs have been issued to solicit applications for the Regional Coordinating Stroke Centers (RFA-NS-13-011) and the National Clinical Coordinating Center (RFA-NS-13-012).  The primary goal of this network is to maximize efficiencies to develop, promote and conduct high-quality, multi-site exploratory phase 1/2 and confirmatory phase 3 clinical trials focused on key interventions, as well as biomarker-validation studies that are immediately preparatory to trials, in stroke prevention, treatment, and recovery with the objective to have a balanced portfolio between all three approaches.  The network will include multiple regional coordinating stroke centers around the U.S. representing a larger number of community stroke centers all coordinated through separate National Clinical Coordinating and Data Management Centers. 

A number of efficiencies will be encouraged through the network, including the sharing of clinical data and other collected biomarkers, such as neuroimaging.  The National Data Center for the network will be responsible for centralizing, harmonizing and coordinating all aspects of data collection for studies conducted in the network.  Projects will be developed both from investigators within the network as well as from investigators or industry partners outside of the network; therefore the data center for the stroke network must be able to efficiently collaborate with all parties.  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.

Key Dates
Posted Date

April 10, 2013

Open Date (Earliest Submission Date)
Letter of Intent Due Date(s)

July 1, 2013

Application Due Date(s)

August 14, 2013, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October, 2013

Advisory Council Review

January, 2014

Earliest Start Date

March 1, 2014

Expiration Date

August 15, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the 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.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the 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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Purpose

The purpose of this funding opportunity announcement (FOA) is to invite applications to participate as the National Data Management Center (DMC) for the NINDS Stroke Trials Network.  The network will develop and conduct high-quality, multi-site phase 1/2 and phase 3 clinical trials, as well as biomarker-validation studies that are immediately preparatory to 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 recovery 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 regional coordinating stroke centers (RCC) 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 DMC.  The network is designed to increase the efficiency and prioritization 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.  

Background

Stroke is a disabling, often fatal and expensive disorder that is a major public health burden.  Globally it is the second leading cause of death, 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 is 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. 

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 1/2 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 NINDS peer review.

Finally, the network will maximize the ability for NINDS 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. 

Research Objectives

The network aims to harness multidisciplinary stroke expertise to collaboratively and efficiently prioritize and 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 the NINDS Neurological Emergencies Treatment Trials Network (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 in the network 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.  The DMC will be responsible for coordinating centralized data collection and sharing of data collected from studies conducted within the network.  They will have statistical expertise in conducting stroke studies necessary to contribute to the development of study data collection forms and to ensure the accuracy of data collected in the network trials.  The DMC will also work with other statistical leaders in the stroke community who will be expected to contribute to the development of new protocols to be conducted within the network. 

Projects conducted within the network will be streamlined and prioritized with the goal of rapidly completing projects and answering questions along the spectrum of stroke clinical care.  Innovative methodology will be encouraged to improve the clinical translation of promising pre-clinical findings into clinical interventions.  In addition, with a centralized model the network may have the opportunity to design studies that compare multiple approaches or interventions that potentially target the same clinical outcome.  Therefore, it is also advantageous if the DMC has statistical expertise or experience in using flexible adaptive statistical methodology to contribute to these objectives. 

Lastly, it is expected that the stroke network will have the opportunity to develop a repository for the collection of neuroimages from studies conducted within the network that should be linked to the clinical data.  Therefore the DMC should also be able to coordinate the centralized collection and sharing of neuroimaging data.    

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.

Network Organization

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 the DMC.  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 Collaborative Research and Development Agreement (CRADA) or from the NINDS through a specific funding opportunity announcement.  Collaborative projects developed by investigators in the network will be strongly encouraged.  For large, simple, acute stroke trials the NCC and DMC of the NINDS Stroke Trials Network may collaborate with the NINDS Neurological Emergencies Treatment Trial (NETT) network to coordinate trial activities. 

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

1)  Data Management

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

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

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

2)  Data Quality Assurance

3)  Data Sharing

4)  Communication

5)  Monitoring

6)  Statistical Support

7)  Collaborating with Other Network Components

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 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-13-011 for more details describing the responsibilities of the stroke network RCC's and RFA-NS-13-012 for more details describing the responsibilities of the stroke network NCC

Regional Coordinating Stroke Centers

The RCC's selected for funding in the network will have both clinical science excellence and specialized expertise in stroke management, a strong background in stroke research, and a proven ability to recruit stroke patients that 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.  The 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

A typical RCC in the network is envisioned as a regional academic medical center or tertiary care facility capable of providing research support for its collaborative stroke centers.  RCCs may choose to include geographically or organizationally linked partners or satellite stroke centers, such as other academic centers and/or private and community hospitals and clinics. Such satellite stroke centers could be venues for additional patient enrollment or might provide access to patient populations not traditionally cared for at the RCC. The RCC will be responsible for providing scientific leadership and regular communication to satellite centers regarding protocols and study progress and for providing administrative and budget support for protocol initiation.  In addition, preclinical stroke activities at the RCC's will contribute to the development of compelling phase 1/2 research applications and also enhance training opportunities.  All centers will be strongly encouraged to increase the value of clinical research data through an aggressive data sharing.

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 PD/PI of the NCC (who will serve as chair), the PD/PI of the DMC, the NINDS Project Scientist, NINDS Program Official, and selected PD/PIs 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/PIs of the NCC and DMC, the NINDS Project Scientist, and the PD/PI or their designees from each of the RCC's.  The Steering Committee will be the main governing body of the network's scientific operation and conduct. 

Network Projects

Over the next 5-year project period, the network will initiate approximately 4-5 NINDS-funded exploratory phase 1/2 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 and complete NINDS-funded projects that were initiated before the network was established.  In such case, the DMC will be expected to work with the statistical and data management group of the ongoing study to harmonize the study with the stroke network centers but may not be expected to manage all the data management activities for the ongoing study.  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 current 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. 

Section II. Award Information
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 scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) 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 one (1) award under this FOA, corresponding to a total of $1,125,000, for fiscal year 2014. Future year amounts will depend on annual appropriations.

Award Budget

The expected direct cost for individual awards is up to $750,000 per project year.  

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.

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

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

Foreign Institutions

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.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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.   

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility


Number of Applications

Only one DMC application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. 

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

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:

Section IV. Application and Submission Information


1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

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: janiss@ninds.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and must be followed, with the following exceptions:

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Facilities and Other Resource: Institutions  must document commitment to the PD/PI by providing departmental and institutional support letters, and 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).  For those 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.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

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

Applicants are strongly encouraged to name an experienced research team that will support the project management and implementation of the network trials, and to list additional research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution.  The applicants are encouraged to assemble a diverse team, which includes women and minorities.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

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

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

PHS 398 Cover Letter

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: The Research Strategy must consist of the following Sections A – H

A) Leadership Plan

The PD/PI should describe how stroke trials and research will be strategically supported by the DMC. The PD/PI should describe the expertise and track record of the research staff, the DMCs SOPs, how tasks will be delegated and supervised, and how the team will communicate. The PD/PI should describe how all aspects of complex multi-center trials will be supported by the DMC.

B) Collaboration and Communications Plan

Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with the RCC's, the NCC, and NINDS and its partners (both academic and industry partners) in all aspects of the network program.  Applicants should describe their communications plan with the NCC and Clinical Sites within the network. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., established database tools, hardware, software, quality control tools, monitoring expertise, team leadership and training, communications platforms, website design and management).  Applicants should also indicate their willingness to attend all network investigator meetings, which will include conference calls one- two times a month and in-person meetings at least one-two times a year.

C) Data Management, Quality Assurance and Monitoring Plan

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

D) Statistical Support Plan

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

E) Plan to Increase Data Sharing Opportunities

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

F) Trial Start-up and Participant Recruitment

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

G) Project Management and Coordination Plan

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

H) Contribution to potential future network trials

Applicants should indicate their willingness to work within the network to propose timely clinical trials to the NINDS.  Investigators awarded a DMC grant will be requested to provide a record of their contributions on each annual progress report 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) an adaptive trial that uses novel approaches to inform interim decision making to streamline the simultaneous evaluation of several potential neuroprotective approaches for acute ischemic stroke, either alone or in combination with other strategies; 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 data management experience with pediatric studies.

Letters of Support: A statement of commitment or 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.

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 SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modification:

The following items are recommended for inclusion in the Appendix:

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.   

6. Other Submission Requirements and Information

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.

Important reminders:
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 by the Center for Scientific Review and responsiveness by NINDS, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.     

Section V. Application Review Information


1. Criteria

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.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?  

Investigator(s)    

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?  Does the PD/PI have a track record in successfully designing and implementing the statistical and data management aspects of multicenter clinical trials in stroke?  Do the investigators provide consistent evidence for collaborative leadership in statistical and data coordination of multicenter trials, and is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA?  

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?  Does the application demonstrate the center's experience with adaptive clinical trial methodologies?  Does the application demonstrate the center's experience with the NINDS stroke common data elements and/or other tools for supporting data sharing?   

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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 the DMC and the NCC, clinical sites and the community clearly described and creatively optimized?  Are the investigators likely to carry-out the key tasks in a timely manner, including, but not limited to establishing the database, data cleaning, analysis, and data sharing?

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?  Does the institution show commitment to the PD/PI by providing departmental and institutional support letters? The institutions 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). Is the center capable of supporting a bio-imaging repository for the network?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.   

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.   

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Data Sharing is reasonable.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), 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. 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 Stroke Council. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information


1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 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 DMCC PD(s)/PI(s) will have the primary responsibility for:

An NINDS Project Scientist will 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.

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Phone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

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

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@ninds.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

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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