Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title	Neurological Emergencies Treatment Trials (NETT) Network Clinical Site Hubs for year 2011 (U10)
Activity Code	U10 Cooperative Clinical Research Cooperative Agreements
Announcement Type	Reissue of RFA-NS-06-009.
Related Notices	None
Funding Opportunity Announcement (FOA) Number	PAR-11-342
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.853
FOA Purpose	The purpose of this funding opportunity announcement (FOA), issued by NINDS, is to invite new and renewal applications to participate as Clinical Site Hubs in the Neurological Emergencies Treatment Trials (NETT) Network. The goal of this existing network is to develop and widely implement efficacious treatments for patients with a broad spectrum of neurological emergencies in order to decrease the morbidity and mortality associated with neurological disease. Their objective is to conduct multiple, large, streamlined phase III clinical trials involving neurological emergencies.

Posted Date	September 20, 2011
Letter of Intent Due Date	November 9, 2011
Application Due Date(s)	December 9, 2011
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	February-March 2012
Advisory Council Review	May 2012
Earliest Start Date(s)	July 2012
Expiration Date	December 10, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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.

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

PURPOSE

The purpose of this funding opportunity announcement (FOA), issued by NINDS, is to invite new and renewal applications to participate as a Clinical Site Hubs in the Neurological Emergencies Treatment Trials (NETT) Network. The goal of this existing network is to develop and widely implement efficacious treatments for patients with a broad spectrum of neurological emergencies in order to decrease the morbidity and mortality associated with neurological disease. Their objective is to conduct multiple, large, streamlined phase III clinical trials involving neurological emergencies.

BACKGROUND

Fifteen million adults and children are seen in U.S. emergency departments annually for acute neurological disorders that vary in seriousness from trivial to life threatening. Most patients are initially evaluated and treated by emergency medicine physicians, not by specialists in neurological diseases. Optimal management in the first hours of neurological emergencies is often critical to recovery; the window of opportunity cannot be reopened later due to the unique vulnerability of the central nervous system.

In order to improve outcomes for patients with neurological emergencies through research aimed at new therapies and their more effective implementation, the NINDS has developed the Neurological Emergencies Treatment Trials (NETT) Network NETT: Welcome. The goal of the NETT Network is: 1) to facilitate high-quality clinical trials in several different types of emergency neurological disorders afflicting adults or children; 2) to encourage collaboration between emergency medicine physicians and neurological disease specialists in trial design and execution; and 3) to facilitate the implementation of new therapies into clinical practice. The purpose of the NETT is to increase the efficiency of clinical research through shared infrastructure that serves as a resource for investigator-initiated clinical research in acute neurological disorders that are funded through traditional NINDS peer-review mechanisms.

RESEARCH OBJECTIVES

The network aims to share expertise in emergency medicine, neurology, and neurosurgury who work together in an efficient manner to conduct large, streamlined phase III NINDS-sponsored clinical trials involving neurological emergencies seen through emergency departments to develop better treatments for patients with acute neurological disorders.

The objective of the network is to streamline the implementation of clinical research in emergency neurological medicine by using standardized master trial agreements and shared resources.

RESEARCH APPROACHES

Shared Network Infrastructure

This FOA encourages applications for funding of infrastructure for NETT Clinical Hub sites. The additional project-specific funds to support the implementation of network protocols are part of separate awards. These funds will be distributed to the Clinical Hub Sites via the Clinical Coordinating Center (CCC) on a per-patient basis, according to protocol budgets approved by the network Steering Committee (SC) and via master trial agreements with the Clinical Sites. The Clinical Sites must be willing to follow this funding arrangement for each trial protocol conducted in the NETT.

The regional Clinical Site Hubs will each coordinate activities at multiple emergency departments (or spokes in a hub-and-spoke model) involving 18-25 emergency medicine physicians, neurologists, neurointensivists, neurointerventionalists, physiatrists, and neurosurgeons, and other surgeons and subspecialists, varying depending on local circumstances. Typical Hubs are envisioned as regional academic medical centers or tertiary care facilities capable of providing research support for the spokes. Spokes will vary in institutional format from academic emergency centers to community hospitals, with the latter serving to expand patient access, to allow assessment of the intervention in a real world practice setting, and to facilitate dissemination of the research results. Depending on the specific trial design, the spokes could either enroll patients on-site, using the Hub for research support, or identify participants for transfer to the Hub for specialty care. The Hubs will provide clinical leadership, research support, and local neurological expertise, coordinate IRB activities and human subject protections, enter data, and manage contracts. Involvement of nonacademic-affiliated hospitals, non-urban hospitals, and hospitals serving minority populations will be considered in Hub selection. Funding for Hubs will be closely linked to research productivity (e.g. recruitment, data quality); the costs of maintaining the infrastructure will be minimized. Representatives of Clinical Site Hubs will selectively participate on the Steering Committee. During the trial, Hubs may be added, deactivated, or placed in a follow-up mode with budget reduction, depending on performance measures like number of trials started, time to start up of trials, quality of data obtained in proportion to error rates, proficiency, and recruitment targets achieved, enrollment of minority populations and requirements for protecting human subjects for all clinical trials.

Hubs will attempt to recruit all eligible patients with entry and follow-up according to the final, approved trial protocols. Training in good research practices is required of all investigators involved at the hub and measures to protect human subjects must be in place. Hubs will cooperate with data audits and other quality control procedures established by Steering Committee and trial protocols. Hubs will ensure timely transmission of all data to the Statistical and Data Management Center and agree to publish NETT Network generated data only with permission of the NETT Network Steering Committee.

It is envisioned that core members of the Hub would include emergency medicine physicians, with the collaboration of neurologists and neurosurgeons, although this may vary depending on local circumstances and should be described and justified. Additional potential involvement and collaboration with intensive care and other acute medicine specialists, physiatrists, radiology/neuroradiology and ambulance systems should be described, both for the hub institution and the proposed spokes. Research experience, the availability of research nurse support, blood and biological specimen processing and storage facilities, and research pharmacy services should be described in the application.

Network Structure and Management

The NINDS Neurological Emergencies Treatment Trials Network includes: one Data Coordinating Center (DCC), one Clinical Coordinating Center (CCC), both of which have been invited under separate FOAs, and up to 17 Clinical Hub Sites to be invited in the current FOA. A network Clinical Hub Site should be able to conduct trials in adult populations, pediatric populations, or both. The function of the coordinating centers is discussed below.

Clinical Coordinating Center

The NETT Network Coordinating Center (CCC) will provide overall leadership for the project, including coordinating the activities of the NETT Clinical Site Hubs, particularly recruitment, follow-up, and data quality. It will initiate investigator training and certification as needed, supervise quality control measures, organize limited on-site monitoring, and coordinate meetings and teleconferences as appropriate among all study investigators. The Clinical Coordinating Center will develop and manage the trial protocols, monitor eligibility of participants, assure compliance with regulations and monitor the informed consent process, supervise and encourage recruitment, prepare blinded reports on adverse events, monitor study execution at sites, and arrange the supply of study medication for the trials. In addition, the Clinical Coordinating Center will collaborate with the Statistical and Data Management Center in developing and implementing data management procedures. The Clinical Coordinating Center will be responsible for quarterly progress reports to the NINDS, the NINDS-appointed NETT Network Advisory Group, and one or more DSMBs.

Statistical and Data Management Center

The NETT Network Statistical and Data Management Center (SDMC) will work with the network leadership to design and implement data entry systems, develop study forms, receive data from the Clinical Site Hubs, perform data checks/queries, undertake interim monitoring, analyses and reporting for the Clinical Coordinating Center, NINDS, and Data and Safety Monitoring Boards (DSMBs). Biostatistical analyses and trial reporting for the network trials will be done through collaboration with the Steering Committee.

Network Projects

Over the next 5-year project period, the network will conduct approximately 4-7 NINDS-funded, large, streamlined phase III clinical trials NETT: Research Studies. The exact number of protocols supported will depend on the nature and extent of the investigations proposed and the availability of funds. Projects conducted through the NETT are submitted using the NINDS PHASE III Investigator-Initiated Multi-Site Clinical Trials FOA (PAR-11-173: NINDS PHASE III Investigator-Initiated Multi-Site Clinical Trials (U01).

Funding Instrument	Cooperative Agreement
Application Types Allowed	New Renewal The OER Glossary and the PHS398 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. Although the financial plans of the IC provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds..
Award Budget	The maximum allowable direct cost per year for a NETT Hub will be $200,000. The total number of years that may be requested for this program is 5 years.
Award Project Period	This is a one-time FOA to fund the network for 5 years. Plans beyond the current funding period are undetermined.

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

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant organizations must complete the following registrations as described in the PHS398 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.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Director(s)/Principal Investigator(s) (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 four (4) 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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) for a Clinical Hub Site must have clinical trials experience with a track record in successfully implementing clinical trials.

• Institutions will be required to document commitment to the PD(s)/PI(s) 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(s)/PI(s) and/or Clinical Site).
  
  
• Core members of the Hub should include emergency medicine physicians, with the collaboration of neurologists and neurosurgeons, although this may vary depending on local circumstances and should be described and justified. Additional potential involvement and collaboration with intensive care and other acute medicine specialists, physiatrists, radiology/neuroradiology and ambulance systems should be described, both for the hub institution and the proposed spokes. Research experience, the availability of research nurse support, blood and biological specimen processing and storage facilities, and research pharmacy services should be described in the application.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Renewal applications are permitted in response to this FOA.

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 PHS398 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:

• Descriptive title of proposed research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Scott Janis, PhD
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)
Telephone: (301) 496-9223
Fax: (301) 402-0182
E-mail: [email protected]

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed. Sub-sections of Section 3. Research Strategy of the PHS 398 Research Plan will include sub-sections A D and standard page limits for the Research Strategy as follows:

A. Program Overview - 4 pages
B. Research Program - 4 pages
C. Leadership - 2 pages
D. Administrative Core - 2 pages

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Section 3. Research Strategy must consist of the following new sub-sections A D (see details below).

Other sections of the PHS 398 Research Plan remain unmodified and should be completed following standard instructions.

NOTE: An application from a currently funded NETT Hub (renewal application) must include a progress report under Section 3. Research Strategy, sub-section A Program Overview.

A. Program Overview

• Background and Experience. Describe the group’s history and experience in conducting NINDS-sponsored clinical trials, in particular, Cooperative Group trials. The application should provide details of experience working together as a group, particularly in implementing clinical trials in acute neurological injuries and related activities.
• Catchment Area. The application must delineate its catchment area. Inlude 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 Hub has more than one component/affiliate institution, describe the relationship of component(s)/affiliate(s) to each other and to the Hub site. Include the distance between these institutions (including administrative office and shared resources) and location of proposed personnel.

The availability of facilities, including laboratories, inpatient and outpatient resources, EMS units, etc., must be described. In the Resources/Facilities section, applicants should discuss their capability to participate in a distributed data entry system, since Clinical Hubs should be able to interact with the Data Coordinating Center to transmit and edit data. The applicant should describe in the Resources/Facilities section how local clinical research resources such as equipment, space and research staff will relate to the network, and, if applicable, how the network will integrate CTSA resources.

A statement of commitment from each participating institution or organization (Note: Include letters of institutional commitment under Research Plan section Letters of Support (e.g., Consultants)) and/or documentation of consortium arrangements must be provided (Note: Include Letters of Intent to Establish a Consortium under Research Plan Section "Letters of Support"). In adddition 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 NETT Hub 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 NETT Hub 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 attached confirming this commitment.

Involvement of Emergency Medicine: Emergency medicine must be fully integrated into the leadership of the NETT Hub and the patient access plans. It is likely that many individuals representing different medical specialties, organizations and hospital departments will be part of a successful NETT Hub. These include: the emergency medical system, the hospital emergency departments, radiology facilities, intensive care units, patient coordinators, neurologists, neurosurgeons, radiologists, patient advocates, and patient educators. Central to the treatment of acute neurologic disorders is the emergency department where initial contact with most patients is made and the early diagnostic and treatment activities occur. Hence, involvement of the leadership of participating emergency departments is a requirement. Naturally, the organization best suited to rapidly evaluate and treat acute neurological disorders varies according to the local availability of resources, and therefore, a specific emergency physician role is not specified. What is required is clear evidence of involvement of emergency physicians that will ensure the most rapid possible treatment of these patients and the development of new procedures and treatment that are broadly applicable.

• Progress (Renewal Applications only). Include a progress report describing the group’s accomplishments relative to participation in NINDS-NETT over the current funding period (i.e., 5 years). This should include: 1) list the progress and achievements specific to the application since the previous competitive review; 2) summarize the Hubs efficiency in starting new trials (e.g., IRB submission, approval, Exception from Informed Consent (EFIC), etc.); 3) summarize efficiency of enrollment at their Hub in the ongoing or completed NETT trials NETT: Research Studies; 4) describe the timeliness and accuracy of data entry into the SDMC web data system; 5) describe team contributions of the site PD(s)/PI(s) leadership, participation in network activities, attendence at meetings, etc.; and 6) describe how the presence of the NETT Hub award has facilitated performance in the NETT clinical trials.
  
  
• Relevant Accomplishments (New Applications only). Describe the group s accomplishments relative to implementing acute neural injury clinical trials in the group’s practice setting(s) and provide a detailed summary of the group s accrual to these trials. Describe the group’s contributions to the research agenda of its affiliated cooperative groups during the past 3 years (if any). This should include efficiency of starting these trials (e.g., IRB submission, approval, EFIC, etc.), the timeliness and accuracy of data entry to the trial, and efficiency of enrollment. If they are currently enrolling in one of the NETT trials (NETT: Research Studies) as a non-NETT site, they should include performance metrics for that trial in the application.

B. Research Program

Research Plans. The application should describe the group’s plans and approach to implementing and conducting NETT-approved clinical trials (NETT: Research Studies) 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 Hub Group 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 Clinical Sites, the Data Coordinating Center, 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 in the Research Strategy section of the application on outreach and collaboration with other clinical investigators at the Clinical Site, because the success of the network at the Clinical Site will depend on collaboration with co-investigators with disease-specific clinical research expertise and a clinic population who are interested in working with the PD(s)/PI(s).

Applicants should indicate their willingness to attend all network investigator meetings, which will include conference calls at least two times a month and in-person meetings at least three times a year.

Applicants should discuss their willingness, and that of the institutions involved, to establish standardized master trial agreements with the Clinical Coordinating Center to reduce trial start-up time.

The applicant should decribe their plans and efficiency for starting new trials, including IRB review and approval, establishing contracts, means to monitor and track performance and increase recruitment and retention of subjects, etc. In addition they should include their experience with using EFIC in clinical trials and for getting IRB approval for using EFIC in their community.

The application should include a plan for how the PD(s)/PI(s) will monitor performance and collect data on start up, recruitment and retention for new and potentially also for ongoing NINDS-funded clinical trials at the Hub and Spokes Sites.

• Accrual Plans: Renewal applicants must demonstrate that their Hub and Spoke consortium has enrolled at least 50 participants into the NETT trials during their initial funding period. An established Research Base is expected to have met or exceeded the stated minimal number of accruals and/or have a credible plan for increasing accrual throughout the next funding period. Unique challenges at their Hub that created challenges in starting or enrolling in NETT trials should be discussed with plans and recent evidence that these challenges have been overcome.

A new application must demonstrate that the proposed Hub can meet the accrual minimums by the end of the first competing project period. The applicant should provide evidence of their capability related to its previous history in accruing to acute neural injury clinical trials and specifically discuss their ability to enroll participants into current enrolling NETT trials (NETT: Research Studies). Evidence must be presented of their ability to enroll and administer an acute neural treatment in the emergency room or in the EMS setting and their ability to use EFIC in their Hub sites where necessary. If they are a site in a current NETT trial they should provide their accural performace in the trial.

C. Leadership

• Key/Senior Personnel. A designated PD(s)/PI(s) is required. A substitute PD(s)/PI(s) candidate should be identified to assure continuity in the event of resignation of the PD(s)/PI(s). The qualifications and experience of both persons must be described, specifically documenting their respective abilities to organize and manage a hub in the acute neural setting of the Neurological Treatment Trials Network, as well as experience in accruing patients/participants to clinical trials. In addition, the application should describe the strategy used by the PD(s)/PI(s) and Institutional official to delegate leadership responsibility with respect to the trials selected for activation by the NETT and how the responsibility is delegated among key/senior individuals. Evidence of Emergency Medicine should be present in the leadership role(s).

As the leader of the Hub, it is expected that the PD(s)/PI(s) plays a leadership role in some capacity to the community served by the Group. The application should describe the leadership role played by PD(s)/PI(s) and other Senior/Key personnel (if applicable) and the impact it has on the success of the Hub as well as on the overall community.

In addition, the application should describe the leadership positions held by the PD(s)/PI(s) with the Hub’s affiliated research bases as well as contributions made in that position along with its impact. Parallel descriptions should be given for other Senior/Key personnel, if applicable.

A mentoring plan or program for leadership succession within the Hub Group 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 emergency medicine physicians, neurologists, neurointensivists, physiatrists, and neurosurgeons, and other surgeons and subspecialists, varying depending on local circumstances, as appropriate. A description of the team, how they operate and interact and how they lend their expertise to achieve the goals of the Hub Group should be provided.

D. Administrative/Data Management Core

• Operations. The application should describe the Hub'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 Hub 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 Hub should be described. Assurance of quality is the joint responsibility of the Hub and its affiliated spokes. Procedures for data collection and investigational drug monitoring must be described in the application. For data management procedures, include details on 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 spokes if required; and are systems are in place for electronic data transfer.

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 PHS398 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 PHS398 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 PHS398 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, NIH. Applications that are incomplete will not be reviewed.

Budget:

Budget requests may include the following allowable items:

• Partial support for the PD(s)/PI(s) and Associate PD(s)/PI(s) salary but ONLY for time spent on Hub organizational/administrative tasks;
• Salary support for full or part-time research nurses, administrative personnel, data managers, and study assistants;
• Travel to meetings directly related to study activities (e.g., research base meetings, NINDS or NETT-sponsored strategy sessions/workshops, local travel); and
• Special personnel resources needed to support the recruitment and retention of eligible patients on clinical trials.

The following items are NOT allowed in the budget requests:

• Costs of clinical care provided to patients (e.g., for patient care reimbursement, transportation costs);
• Data Coordinating Center or Clinical Coordinating Center costs nor costs for training, investigator meetings, or patient enrollment, treatment or follow-up.
• Salary support for clinical support personnel for the NETT-approved trials; and
• Physician compensation (other than specified above for PD/PIs and associate PD/PI for their NETT-related administrative activities).

The total should not exceed $200,000 direct costs per year in years 1-5 (all of which will be 12-month project years). The release of funds will be milestone-driven, according to milestones to be specified in the Notice of Award. Clinical Sites who will not meet the milestones would be terminated, if necessary. Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation (see NOT-OD-05-004). All costs in the proposed budget should include appropriate justification.

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/priority score to reflect their assessment of the likelihood for the proposed NETT Hub 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 Hub 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 Hub that by its nature is not innovative may be essential to advance a field.

Significance

Does the Hub address an important problem or a critical barrier to progress in the field? If the aims of the Hub 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 clinical Hub site contribute to the advancement of clinical research and clinical trials within the framework of the NETT network?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Hub site? 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 Hub is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the PD(s)/PI(s) have a track record of working collaboratively? Is there evidence of a strong relationship between Emergency Medicine and Neurology/Neurosurgey? Does the PD(S)/PI(s) have a track record in successfully implementing clinical trials in emergency medicine? 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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Hub? 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 Hub 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 site clearly described and creatively optimized? Does the investigator have adequate plans to recruit patients with acute neurological disorders and with diverse gender/minority representation, as well as plans for human subjects' protection, good clinical practices (GCP)? Is the investigator willing and likely sufficiently available to participate in network-wide meetings, teleconferences, and SC working groups? Is the timeline for IRB approvals and contract negotiations sufficient? Is the institution able to utilize a standard network standardized master trial agreements for per-patient cost of clinical programs?

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 Hub 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(s)/PI(s) (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD(s)/PI(s))? Is there evidence that this site can substantially recruit patients for trials conducted in the NETT?

As applicable for the Hub proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority 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 neural emergency clinical trials and working together as a group in implementing clinical trials? Is the overall team of professionals participating in the Hub 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 Hub Group see enough patients to ensure that the Hub Group will be able to meet or exceed the accrual requirements in the NETT-approved clinical trials?
• Organizational Structure. How appropriate is the planned organizational structure to accomplish 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?
• Progress (Renewal Applications). How significant was the involvement and/or contributions to collaborative activities within the NETT network? How successful was the Hub in meeting or exceeding the minimum annual accrual goals?
• Relevant Accomplishments (New Applications). How relevant are the group’s accomplishments in implementing clinical trials in neural emergencies in the group’s practice setting(s) to the goals and requirements for the NETT?

B. Research Program

• Research Plans. Are the Hub group’s plans for implementing NETT-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 Clinical Coordinating Center?

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 Hub Group (or new Group applicants) in engaging the community served? How relevant are these activities to the goals and roles of NETT?

Are the affiliations of the Hub Group with their spoke sites appropriate and consistent with the rationale provided in the application?

• Accrual Goals. Are the proposed participant accrual plans matching the history of accrual by the applicant team, the overall size of the proposed Group, and the catchment area served? What is the likelihood that the applicants will be able to achieve the required minimal numbers of 50 participants per year recruited into NETT trials over the proposed project period? Are they capable of achieving significantly higher levels of accrual?

C. Leadership

• Key/Senior Personnel. Are the qualifications, training, and experience of the PD(s)/PI(s) /associate PD(s)/PI(s) appropriate for organizing and managing a research program that includes accrual to NETT-approved trials as well as related activities?

Has the PD(s)/PI(s) demonstrated effective leadership abilities in the community served by the Hub Group and/or to the affiliated spokes? Have other Key/Senior personnel taken on leadership roles that contribute to the success of the Hub and/or the research agenda of the affiliated spokes?

D. Administrative/Data Management

• Operations. Are the management structure, 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 Hub 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

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable.

As applicable for the Hub 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/priority 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 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. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review), will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review;
• Availability of funds;
• Relevance of the proposed project to program priorities;
• Clinical trial expertise, track record, and resources;
• Track record and willingness to collaborate with other clinical researchers at the applicant’s institution, breadth of expertise among potential co-investigators;
• Willingness, and evidence of potential, to participate in all aspects of the network program, including protocol development and other SC working groups, and participation in teleconferences and in person meetings;
• Willingness to work collaboratively and strong track record of successful collaboration and participation in large, multi-center research teams;
• Recent and current NINDS-funded projects in the clinical neurosciences at the applicant’s institution;
• Ability to begin operations immediately;Agreement to accept the Cooperative Agreement Terms and Conditions of Award delineated in this FOA (see Section VI.2.A);
• Geographic balance of Clinical Center awardees;
• Access to pediatric and/or adult patient populations with a wide range of neurological disorders;
• Diversity of study populations among Clinical Center awardees, as well as balance between pediatric and adult populations, and access to minority populations.

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, CCR 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:

• Trial participant safety, implementation of network protocols in accordance with GCP and other regulatory requirements, participant recruitment and retention, reporting to the NINDS, CCC, DCC, and DSMB.
  
  
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NINDS staff working with the network investigators will develop performance milestones for clinical sites. Failure to meet the agreed upon milestones may result in reduced funding or early termination of the cooperative agreement.
  
  
• An NINDS Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.
  
  
• An agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• A SC composed of three Clinical Site principal investigators representing the Clinical Sites, the Data Coordinating Center principal investigator, the Clinical Coordinating Center principal investigator, the PD(s)/PI(s) of active network projects, and the NINDS Project Scientist will be the main governing body of the network. The NINDS will appoint a SC Chair who may or may not be independent of the Clinical Sites, the CCC and the DCC to preside over SC meetings and serve as the SC representative.
  
  
• The Clinical Site PD(s)/PI(s) and coordinator are expected to participate in all network teleconferences and investigator meetings. They are also expected to assist the network SC in deciding how peer-reviewed research and trial proposals will be selected and prioritized for implementation through the network.
  
  
• Clinical Site PD(s)/PI(s) will also be expected to serve on SC working groups established on an as-needed basis and charged with tasks such as the planning and development of protocols, publication guidelines, quality assurance monitoring, etc.

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) 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 theNIH 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.